1. title pages - shodhgangashodhganga.inflibnet.ac.in/bitstream/10603/13579/10/10_chapter 3.… ·...

129

Chapter-IIIa Synthesis of new 1,3,5-triphenyl-

bispyrazolines linked via the 3-aryl ring

� Synthetic and biological studies of pyrazolines and related heterocyclic

compounds

Mohamad Yusuf and Payal Jain

Arabian Journal of Chemistry 2011, doi: 10.1016/j.arabjc.2011.09.013.

� Synthesis, characterization and antimicrobial studies of new

bispyrazolines linked via 3-aryl ring with aliphatic chains


Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy 2012,

96, 295-304.

130

The studies of heterocyclic compounds had been subject of the major attraction in the

past decades due to their occurrence in nature and numerous applications in the

biological systems.1 The derivatives of chalcones are the significant compounds

which are associated with a wide range of pharmaceutical activities.2-11 Chalcones are

the compounds having 1,3-diaryl-2-propene moiety, containing an olefinic, ketonic

and hydroxy group.2,4,6 The condensation reaction of nitrogen containing

binucleophilic reagents with chalcones is one of the most convenient method for the

synthesis of five, six and seven membered heterocyclics.12-30 Among the five

membered heterocyclics, pyrazolines have played a crucial part in the development of

heterocyclic chemistry and have been extensively used as the important synthones in

organic synthesis.30-34 Pyrazoline system has been found to be biological active and is

the significant constituent of many pharmaceutical and agrochemical products. In

particular their derivatives are extensively used as antitumor, antibacterial, antifungal,

antiviral, antiparasitic, antitubercular and insecticidal agents.35-44 The pyrazoline

derivatives are also reported for their antihypertensive, anti-inflammatory,

antidepressant, antiarthritic and analgesic activities.45,46

3,5-Diaryl-1H-pyrazoles 3.4 were prepared47 from the cyclization of 1,3-diketone 3.3

with hydrazine hydrochloride (Scheme-3.1).

+ NNH

Ar'

ArLiHMDS, toluene NH2NH2.HCl, EtOH

3.1 3.2 3.33.4

Ar C CH3

O

Ar' C Cl

O

Ar C

O

CH2 C Ar'

O

Scheme-3.1

The reaction48 of dibenzalacetone 3.7 with hydrazine hydrate and formic acid yielded

a novel 2-pyrazoline 3.8 (Scheme-3.2).

CHO +CH3

CH3

OCH CH C CH CH

ONaOH/ EtOH

NN

O

H

NH2NH2/ HCOOH

3.5 3.63.7

3.8

Scheme-3.2

131

A new series of pyrazolines 3.12 and isoxazolines 3.13 have been synthesized49 from

the reaction of 1-(4’-substituted phenyl)-3-(6’’-methoxynapthaline)-2-propene-1-one

3.11 with hydrazine hydrate and hydroxylamine hydrochloride respectively

(Scheme-3.3).

R

CH3

O

+O

H

OCH3

R

O

OCH3

R

NNH

OCH3

R

NO

OCH3

MeOH, NH2NH2.H2O NH2OH. HCl

KOH/ MeOH

3.93.10

3.11

3.133.12

Scheme-3.3

1,3,5-Triaryl-2-pyrazolines 3.1650 have been prepared from the reaction of chalcones

and phenyl hydrazine hydrochloride (Scheme-3.4) in the presence of sodium acetate-

acetic acid aqueous solution under ultrasound irradiation.

Ar1

O

Ar2 +NHNH2.HCl

N

N

Ar1

Ar2

CH3COONa/ AcOH/H2O

a) Ar1=C6H5, Ar2=4-CH3OC6H4 b) Ar1=C6H5, 4-CH3C6H4 c) Ar1=C6H5, Ar2=C6H5 d) Ar1=C6H5, Ar2=4-ClC6H4, e) Ar1=C6H5, Ar2=3-ClC6H4, f) Ar1=C6H5,

Ar2=2-ClC6H4, g) Ar1=C6H5, Ar2=3-BrC6H4, h) Ar1=C6H5, Ar2=4-O2NC6H4, i) Ar1=4-ClC6H4, Ar2=C6H5, j)Ar1=3-O2NC6H4, Ar2=C6H5,

3.14 3.15 3.16

ultrasound

Scheme-3.4

Some biologically significant bisheterocycles51 bearing pyrazoline moiety 3.20 have

been obtained starting from pyrazolyl aldehyde 3.17 through the sequence of reactions

which are described in Scheme 3.5.

132

N

NH

Cl

CHO

CH3

N

N

Cl

CHO

CH3

CN

N

NCH3

CN

NNH

PhCl

N

NCH3

CN

NN

Ph

X

Z

Cl

Br

NC

PhNHNH2/ NaOAc

CAT, EtOH

CH2

CX Z

X = H, CH3, H, H, H, H, H, H

Z= Ph, Ph, CH3CN, CH2Cl, CH2Br, CH2OH, COOMe, COOEt

3.17 3.18

3.193.20

K2CO3/ DMF

Scheme-3.5

The analgesic and anti-inflammatory properties of novel 3/4-substituted-5-

trifluoromethyl-5-hydroxy-4,5-dihydro-1H-1-carboxyamidepyrazoles 3.22 (where

3/4-substituent are H/H, Me/H, Et/H, Pr/H, i-Pr/H, Bu/H, t-Bu/H, Ph/H, 4-Br-Ph/H

and H/Me) were determined52 and these compounds were prepared in the exploration

of the bioisosteric replacement of benzene present in salicylamide with a

5-trifluoromethyl-4,5-dihydro-1H-pyrazole scaffold (Scheme-3.6).

R1

OR

CF3

O

R2

NN

R1R

2

F3C

OH

O NH2

NH2NHCONH2.HCl/ MeOH/ Pyridine

3.213.22

Scheme-3.6

The cyclocondensation reaction53 of chalcone 3.23 and isoniazid led to the formation

of 3-substituted 4,5-dihydropyrazole 3.24 (Scheme-3.7).

CX3R

1

OMeON

N

ON

OH

CX3

R1

/ MeOH

R1= H, Me, Ph, 4-MePh, 2-thienyl, 2-furnyl, 4-MePh, 2-thienyl, 2-furyl ; X= F, Cl

3.23

3.24

NH2 NH C C6H4N

O

Scheme-3.7

133

The pyrazolines 3.29 are prepared54 from the reaction of chalcones 3.26 with

hydrazine hydrate followed by condensation with appropriate aryl isothiocyanate

(Scheme-3.8).

CH3

OH

CH3

O

+ RCHO

CH3

OH

O

R

NHN

CH3

OH

R

NN

CH3

OH

R

NH

SCH3

NH

SOCH3

NN

CH3

OH

R

NCS

CH3

NCS

OCH3EtOH

EtOH

EtOH/ NaOH EtOH/ NH2NH2.H2O

3.25 3.263.37

3.28 3.29

Scheme-3.8

The N-substituted pyrazolines55 3.43 have been synthesized are prepared starting from

the aromatic aldehyde 3.40 through the two step reactions which are shown in

Scheme-3.9.

+N

CONHNH2

AcOH

NaOH/ EtOH

3.40 3.41 3.42

3.43

Ar C H

O

Ar C CH3

O

Ar CH CH C Ar'

O NN

Ar

Ar'

CH2

N

Scheme-3.9

The synthesis56 of novel 3,5-diaryl-pyrazolines 3.45-3.49 have been investigated in

order to study their monoamine oxidase (MAO) inhibitory properties (Scheme-3.10).

134

OH O R

R'

OH

N N

R

R'

NH2

S

OH

N N

R

R'

NHNH

OH

OH

N NH

R

R'

OH

N N

R

R'

O

OH

N N

R

R'

S O

O

R2

R=OH, H; R1= H, OH; R2= CH3

PhCOCl, pyridine, reflux

/

EtOH

CH3I/

R2-C6H4SO2Cl, THF

3.44

3.453.46

3.47

3.48

3.49

NH2NH2.H2O, EtOH

NH2OH

NH2 NH C NH2

S

Scheme-3.10

3,5-Diarylcarbothioamide-pyrazolines 3.53-3.55 designed as mycobactin analogs

were reported to be potent antitubercular agents under the iron limiting conditions.57

These compounds were obtained via the usual reactions which are shown in

Scheme-3.11.

CH3

OR

R1

OR

R1

R2

R3

R4N N

H

R1 R R2R3

R4

N N

R1 RX

NH

S

R5

R6

N N

R1 R R2R3

R4

NH2

S

N N

R1 R R2R3

R4

NHS

R5

R6

X= O, S

3.50 3.513.52

3.533.54

3.55

a b

c

de, b, c

a) i: R2, R3, R4-C6H2-CHO/ aq. NaOH ii) HCl; b) NH2NH2/H2O/EtOH c) R5/R6-C6H3-NCS/EtOH d) NH2NHCSNH2, NaOH/MeOH/HCl e) thiophene-2-carboxaldehyde or furfuraldehyde

Scheme-3.11

135

The cyclization of chalcones 3.58 with 2-(quinolin-8-yloxy)-acetohydrazide 3.59

under basic condition58 led to the formation of new pyrazoline derivatives 3.60

(Scheme-3.12).

Scheme-3.12

Some more synthetic methods have been reported in literature upon the synthesis of

biologically significant pyrazolines.59-69

Bispyrazolines are the molecules which are formed by joining two pyrazoline

moieties together through the alkyl chains of varying lengths. It is evident from the

above literature survey that chalcones are very important synthones in the

heterocyclic synthesis and these intermediates may be used for the preparation of

bisheterocyclics. By keeping these aspects in view, investigations have been focused

upon the cyclization reaction of new bischalcones 3.64-3.69 built around the aliphatic

chains of varying lengths.

CH3

O

R1 +H

O

R2

O

R1 R2

NOH

NO

O O CH3

NO

O NHNH2

+

NN

N

O

O

R R

NaOH/ EtOH

NaOH/ EtOH

ClCH2COOEt, K2CO3, Acetone

N2H4.2H2O

3.56 3.57

3.58

3.59

3.60

3.61

3.62

3.59

136

O CH2 (CH2)n CH2 O

O O

3.64-3.69

n = 2, 3, 4, 6, 8, 10

The bisheterocyclics 3.70-3.75 required for this study were prepared starting from

chalcone 3.63 which was obtained from the Claisen-Schmidt70 reaction of

o-hydroxyacetophenone with benzaldehyde (Scheme-3.13). The decomposition of the

resulting reaction mixture into iced HCl provided a crude product which was

crystallized from MeOH to yield pure compound 3.63 (82%, m.p. 55-57οC).

OH

O

CH3 +NaOH/ EtOH/ O0C

12

31'

2'3'

4'

5'

6'

H

O

OH

O

1''

2''

3''

4''

5''

6''

3.63

Scheme-3.13

The IR spectrum of 3.63 showed strong absorptions at 3216, 1695 and 1604 cm-1 due

to O-H, C=O and C=C stretching frequency respectively. In its 1H-NMR spectrum

(400 MHz, CDCl3), the lowest downfield resonance was placed at δ 12.81

(1H, exchangeable with D2O) that can be ascribed to OH proton. The double bond

protons H-3 and H-2 were very well resonating at δ 7.91 (1H, d, Jtrans=15.5 Hz) and

7.65 (1H, d, Jtrans=15.5 Hz) respectively. The hydrogens belonging to phenyl rings

were centred at 7.68 (2H, dt, J=1.0, 2.8, 4.4 Hz, H-2’’, 6’’), 7.51 (1H, td,

Jm,o=1.6, 7.2 Hz, H-4’), 7.44 (3H, m, H-3’’, 4’’, 5’’), 7.04 (1H, dd, Jp,o=1.0, 8.4 Hz,

H-5’) and 6.95 (1H, td, Jp,o=1.1, 8.1 Hz, H-3’). The most upfield appearance of H-3’

as compared to other protons could be ascribed to the + I effect of the 2’-OH group.

Finally, structure of 3.63 was confirmed from its GC-MS spectrum which exhibited

the molecular ion at m/z 224 (68%).

Synthesis of bispyrazolines 3.70

The compound 3.70 was obtained in two steps:

(i). Synthesis of bischalcone 3.64

137

The chalcone 3.63 was treated with 1,4-dibromobutane in the presence of anhydrous

K2CO3 and tetrabutyl ammonium iodide (PTC) in dry acetone under refluxing

conditions (Scheme-3.14). After completion of reaction, the resulting mass was

poured into iced-HCl to provide a solid substance which was crystallized from

CH3OH:CHCl3 (3:1) to yield pure compound 3.64 as a yellow solid

(69%, m.p. 92-94oC).

OH

O

12

3

2''3''

5''6''6'

5'

4'

3'4''

3.63

K2CO3/acetone/ Br-(CH2)4-Br/Bu4N+I-/ ∆

12

31'

2'3'4'

5'6'

1''2'' 3''

4''

5''6''

O CH2 (CH2)2

O

CH2 O

O

3.64

Scheme-3.14

The compound 3.64 in its IR spectrum exhibited major bands at 1660 (C=O), 1596

(C=C), 2930, 2862 (methylene C-H) and 1230, 1025 (C-O). 1H-NMR (400 MHz,

CDCl3) spectrum of 3.64 was consistent to the proposed structure and confirmed the

symmetry in molecule. The most downfield resonance appeared as a two protons

doublet of doublet (Jm,o=1.7, 7.6 Hz) at δ 7.62 which could be ascribed to H-6’ while

protons H-4’, H-5’ & H-3’ produced three signals at δ 7.42 (2H, ddd,

Jp,m,o=1.0, 1.8, 7.4 Hz), 7.02 (2H, td, Jp,o=0.7, 7.4 Hz) and 6.82 (2H, d, Jo=8.2 Hz)

respectively. Two broad doublets centered at δ 7.52 (2H, Jtrans=15.9 Hz) and 7.31

(2H, Jtrans=15.9 Hz) could be represented by trans hydrogens H-3 and H-2

respectively. The protons belonging to C-3 phenyl ring were resonating at δ 7.50

(4H, m, H-2’’, 6’’) and 7.34 (6H, m, H-3’’,4’’, 5’’). In the aliphatic region, two

triplets integrating for four hydrogens each were observed at δ 3.90 (4H, Jvic=6.2 Hz,

OCH2CH2) and 1.88 (4H, Jvic=6.2 Hz, OCH2CH2).

138

In the 13C-NMR (100 MHz, CDCl3) spectrum of 3.64, signal of the C=O group was

observed at δ 192.80. The carbon atoms belonging to double bond resonated at

δ 142.62 (C-3) & 112.71 (C-2) and the downfield occurrence of former can be

ascribed to its β-position in the enone system. Other noticeable resonance present at

δ 157.50 could be furnished by C-2’ due to its direct linkage to the electronegative

oxygen atom. The remaining aromatic carbon atoms were found to be placed at

δ 134.67 (C-4”), 133.78 (C-1’), 129.40 (C-6’), 128.61 (C-2”, 6’’), 128.24 (C-4’),

127.25 (C-5’) and 120.51 (C-3’’, 5”). The upfield appearance of the C-3’ at δ 112.23

could be ascribed to its ortho placement with respect to C2’-OCH2 group. The

intervening chain furnished two signals at δ 67.70 (OCH2CH2) and 26.04 (OCH2CH2).

ESI-MS spectrum of 3.64 also corroborated its structure which exhibited (M+Na) ion

at m/z 525 (11%) along with other significant ions at m/z 279 (70%), 130 (76%),

93 (100%) and 77 (23%). Its mass fragmentation pattern has been depicted in

Chart-1.

(ii). Cyclization of bischalcone 3.64

The compound 3.64 was refluxed with phenyl hydrazine in EtOH/AcOH medium

(Scheme-3.15) and cooling of the resulting reaction mixture provided a solid

substance. The crude product was crystallized from MeOH to yield pure bispyrazoline

3.70 (63%, m.p. 130-132oC).

1'

3'

4'

5'

6'

2'O CH2 (CH2)2 CH2 O

O O

12

3

1''

2'' 3''

4''

5''6''

3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)2 CH2 O

NN

HX

HMHA

HM

HA

HX

PhNHNH2/ EtOH/ AcOH /∆

3.64

3.70

Scheme-3.15

139

O CH2 (CH2)2 CH2 O

O Om/z 502

O

O

H2C (CH2)2 CH2 O

O

O

O

CH2

O

O

O

HC

....

....

....

....

....

....

.....

m/z 223 (80%)m/z 279 (70%)

m/z 147 (13%)

m/z 93 (100%)

m/z 207 (42%)

m/z 77 (23%)

m/z 130 (76%)

++

+

+

++

+.

a

a

b

b

-C6H4

m/z 525 (M+Na, 11%)

.+

-C15O2H11

-C4H8

-O

-O

-C6H5

Chart-1

IR spectrum of 3.70 was very helpful to interpret its structure which did not exhibit a

strong absorption at 1660 cm-1 indicating the involvement of carbonyl group during

the cyclization reaction of 3.64. Here significant band was observed at 1598 cm-1 due

to the C=N moiety of pyrazoline ring.

In the ESI-MS mass spectrum of 3.70, (M+1) ion was observed at 683 (18%) and its

mass fragmentation pattern has been depicted in Chart-2.

An analysis of 1H-NMR spectrum of 3.70 was helpful to ascertain the symmetrical

feature of molecule. The comparison of 1H-NMR spectra of 3.64 and 3.70 revealed

that the resonances at δ 7.52 (2H, d) and 7.31 (2H, d) present in the former were

found missing altogether in the later which describes the involvement of enone moiety

in the cyclization process. The phenyl ring present at C-3 provided a downfield

140

doublet of doublet at δ 7.92 (Jp,o=1.0, 7.8 Hz) which could be ascribed to H-6’ while

the proton H-4’, H-5’ & H-3’ were observed at δ 7.15 (2H, td, Jm,o= 2.0, 7.8 Hz),

6.82 (2H, td, Jm,o=1.8, 7.6 Hz) and 6.63 (2H, d, Jo=8.4 Hz) respectively. The upfield

appearance of H-3’ as compared to other hydrogens seems to be decided by the

shielding effect of C-2’ alkoxy group. Regarding the protons of the N-1 and C-5

phenyl rings, two multiplets integrating for ten protons each were centred at

δ 7.28 and 6.99 which could be represented by H-2’’, 6’’, 3’’’, 4’’’, 5’’’ and H-3’’,

4’’, 5’’, 2’’’, 6’’’ respectively. The silent feature of this spectrum was the signals of

the pyrazoline ring protons (H-X, H-M & H-A). The non equivalent protons (H-M &

H-A) present at C-4 were resonating at δ 3.94 (2H) & 3.17 (2H) respectively while

H-X was found to be placed at δ 5.14 (2H). The coupling value of JMX=12.1 Hz &

JAX=6.6 Hz describes the cis relationship between H-X & H-M while H-X & H-A are

trans oriented to each other. The geminal coupling value between H-M & H-A was

found to be 17.3 Hz. The downfield occurrence of H-X as compared to H-M & H-A

may be ascribed to its benzylic nature and its placement adjacent to the nitrogen atom.

UV-Vis spectrum of 3.70 exhibited two maxima at 362 and 259 nm which may be

ascribed to n→π* and π→π* transitions respectively.

In the 13C-NMR (100MHz, CDCl3) spectrum of 3.70, the pyrazoline ring carbon

atoms C-3, C-5 & C-4 were present at δ 146.61, 64.35 & 46.74 respectively. The

carbon atoms C-2’ & C-1’’’ which are directly bonded to the hetero atom (O & N)

showed themselves at δ 156.78 and 146.54 respectively. The signals present at

δ 144.95 and 140.92 were assignable to C-1’’ and C-4’’ respectively. The carbon

atoms C-4’, C-6’, C-1’, C-5’ & C-3’ belonging to C-3 phenyl ring resulted suitable

signals at 142.79, 128.95, 122.12, 120.89 and 113.86 respectively. The remaining

resonances in the aromatic region were found to be placed at δ 129.97 (C-3’’’, 5’’’),

128.52 (C-3’’, 5’’), 125.85 (C-2’’, 6’’) and 118.80 (C-4’’’). The carbon atoms

C-2’’’, 6’’’ were resonating at δ 112.27 due to the electron donating effect of the N-1.

The internal chain could provide two signals at δ 67.75 (OCH2CH2) and 26.16

(OCH2CH2) and again the downfield resonances of the former could be attributed to

its direct linkage to the electronegative oxygen atom.

Synthesis of bispyrazoline 3.71

The compound 3.71 was again obtained in the two steps:


141

The chalcone 3.63 was reacted with 1,5-dibromopentane (Scheme-3.16) under the

similar conditions as used earlier for 3.64 to yield pure compound 3.65

(64%, m.p. 89-91oC).

OH

O

K2CO3/acetone/ Br-(CH 2)5-Br/Bu4N+I-/ ∆

1 2

3

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)3

O

CH2 O

O

3.63

5'

4'3'

2'

1'6'

12

31''

2''

3''

4''

5''

6''

3.65

Scheme-3.16

UV-Vis spectrum of 3.65 had two maxima at 289 and 222 nm which may be provided

by n→π* and π→π* transitions respectively. The functional group region of its IR

spectrum had strong absorptions at 1654 (C=O) and 1596 (C=C) cm-1 along with

methylene (C-H) and ether (C-O) stretchings at 2948, 2869 and 1240, 1025 cm-1

respectively.

The 1H-NMR spectrum of 3.65 showed the double bond hydrogens H-3 and H-2 at

δ 7.54 (2H, d, Jtrans=15.9 Hz) and 7.36 (2H, d, Jtrans=15.9 Hz) respectively and the

electophilic nature of β-carbon atom in the enone moiety is responsible for the

downfield resonance of H-3. A doublet of doublet at δ 7.62 (2H, Jm,o=1.7, 7.6 Hz), a

doublet of double doublet at δ 7.40 (2H, Jp,m,o= 0.6, 1.8, 7.4 Hz), a triplet of doublet at

δ 7.00 (2H, Jp,o=0.6, 7.6 Hz) and a doublet at δ 6.82 (2H, Jo=8.2 Hz) were easily

represented by H-6’, H-4’, H-5’ and H-3’ respectively. The protons H-2’’, 6’’ and

H-3’’, 4’’, 5’’ furnished a four hydrogens doublet of doublet at δ 7.50

(Jm,o=2.1, 7.6 Hz) and a six protons multiplet at δ 7.28 respectively. The intervening

chain methylene group OCH2CH2CH2, OCH2CH2CH2 and OCH2CH2CH2 resulted

three signals at δ 3.84 (4H, t, Jvic=6.2 Hz), 1.50 (4H, t, Jvic=6.2 Hz) and 1.30

(2H, quintet, Jvic=3.7 Hz) respectively.

142

NN

O CH 2 (CH 2)2 CH 2 O

NN

H

H

H

H

H

H

NN

O CH 2 (CH 2)2 CH 2 O

NN

H

HH

H

H

-H

+

NN

O CH 2 (CH 2)2 CH 2 O

NN

H

H

+

NN

O CH 2 CH 2 CH 2 O

NH

N

H

H

H

H

H

H

NN

O CH2 CH 2 CH2 O

NN

H

H

H+

NN

O CH 2 CH2 CH 2 O

NN

H

H

H

H

NN

O CH 2 CH2 CH 2 O

NN

H

H

H+

NN

O CH 2 CH 2 CH 2 O

N

C C CH2 O

Ph

Ph

Ph Ph

CH CH CH 2 O

Ph

O

+

m/z 682

m/z 592 (26%)

-C7H6

m/z 591 (10%)

-H

-H

m/z 590 (18%)

m/z 589 (80%)

-H

-NH2

m/z 573 (72%)

-N3H2

m/z 529 (61%)

m/z 511 (18%)

-H2O

m/z 457 (4%)

-C6H7O

m/z 434 (15%)

+

NN

O C C CH2 O

NN

H

H

H

m/z 509 (100%)

-C6H8

m/z 683 (M+1, 18%)

.+

+

+

C C CH 2 O

Ph+

m/z 681 (42%)

m/z 679 (39%)

......

.

......

.

+.

-H2

.

Chart-2

The ESI-MS spectrum of 3.65 exhibited significant ions at m/z 539 (M+Na, 14%),

145 (100%), 144 (29%), 102 (3%), 77 (17%) and its mass fragmentation pattern was

found to be similar as shown in Chart-1 (vide experimental).

The quick examination of 13C-NMR spectrum of 3.65 revealed noticeable signals at

δ 192.94 (C=O), 157.58 (C-2’), 142.67 (C-3) and 112.72 (C-2). The resonances

placed at δ 134.89, 133.60 and 132.26 were easily belonging to C-4’’, C-1’ and C-1’’

143

respectively while carbon atoms C-6’, C-2’’, 6’’, C-4’ & C-5’ appeared at δ 129.62,

128.70, 128.10 and 127.24 respectively. The remaining signals in the aromatic region

were located at δ 120.50 (C-3’’, 5’’) and 112.20 (C-3’). Three different methylene

groups of the intervening chain were found to be resonating at δ 67.73

(OCH2CH2CH2), 29.00 (OCH2CH2CH2) and 25.60 (OCH2CH2CH2).


The compound 3.71 (67%, m.p. 136-138oC) was prepared from the reaction of 3.65

with phenyl hydrazine (Scheme-3.17) under the similar conditions as used earlier for

3.70.

1'

3'

4'

5'

6'


O O

12

3

1''

2''3''

4''

5''6''

3''

4''

5''6''

2''1''12

34

5

5''' 3'''2'''

6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)3 CH2 O

NN

HX

HMHA

HM

HA

HX


3.65

3.71

Scheme-3.17

IR spectrum of 3.71 showed recognizable bands at 1592 (C=N), 2932, 2826

(methylene C-H) and 1240, 1025 (C-O) cm-1. Its ESI-MS spectrum in addition to

molecular ion at m/z 696 (11%), exhibited prominent ions at m/z 695 (19%), 693

(21%), 606 (64%), 605 (28%), 604 (78%), 603 (73%), 587 (58%), 547 (25%), 529

(40%) and 522 (7%). The UV-Vis spectrum of 3.71 had two maxima at 354 and 250

nm due to to n→π* and π→π* transitions respectively.

In the 400 MHz 1H-NMR (CDCl3) spectrum of 3.71, a doublet of doublet integrating

for two protons at δ 7.82 (Jp,o=1.2, 7.8 Hz) could be assigned to H-6’. To the right of

this signal, a ten protons multiplet centered at δ 7.18 appeared due to H-2’’’, 3’’’, 5’’’,

6’’’, 4’ while protons H-2’’, 6’’, H-5’ and H-4’’ were resonating at δ 7.07 (4H, td,

Jm,o=2.1, 7.8 Hz), 6.91 (2H, dd, Jp,o=1.1, 7.8 Hz) and 6.84 (2H, td, Jm,o=1.8, 8.0 Hz)

144

respectively. A triplet of doublet placed at δ 6.81 (2H, Jp,o=1.1, 8.0 Hz) may be

furnished by H-4’’’. Towards the upfield position in the aromatic region, the signals

present at δ 6.72 (4H, td, Jm,o=2.0, 7.8 Hz) and 6.62 (2H, m) were easily given by

H-3’’, 5’’ and H-3’ respectively. The well defined doublet of doublets integrating for

two hydrogens each at δ 5.09 (JXM=12.1 Hz, JXA=7.0 Hz), 3.73 (JMX=12.1 Hz,

JMA=17.3 Hz) and 3.20 (JXA=7.0 Hz, JAM=17.3 Hz) were certainly generated by

pyrazoline ring hydrogens H-X, H-M & H-A respectively. The internal alkyl chain

also provided suitable signals at the expected position in the aliphatic region

(vide experimental). 13C-NMR spectrum of 3.71 also corroborated the proposed structure which had

pyrazoline ring carbon atoms (C-3, C-5 & C-4) at δ 146.54, 64.30 & 46.70

respectively. The internal chain methylene groups furnished three signals at δ 67.72

(OCH2CH2CH2), 29.00 (OCH2CH2CH2) & 26.51 (OCH2CH2CH2). The carbon atoms

belonging to three phenyl rings (N-1, C-3 & C-5) were also resonating at suitable

positions in the aromatic region (vide experimental).




The bischalcone 3.66 was obtained from the reaction of 3.63 with 1,6-dibromohexane

(Scheme-3.18) under the similar conditions as described earlier for 3.64

(77%, 82-84oC).

OH

O


12

3

1'

2'3'

4'

5'6'

1''

2'' 3''

4''

5''6''

O CH2 (CH2)4

O

CH2 O

O

3.63

5'

4'3'

2'

1'6'

12

31''

2''

3''

4''

5''

6''

3.66

Scheme-3.18

145

IR spectrum of 3.66 displayed major absorptions at 1659 (C=O), 1603 (C=C), 2937,

2870 (methylene C-H) and 1236, 1040 (C-O). Its 400 MHz 1H-NMR (CDCl3)

spectrum was similar to that of 3.64 and 3.65 except those of internal chain methylene

hydrogens which were resonating at δ 3.78 (4H , t , Jvic=6.2 Hz, OCH2CH2CH2), 1.58

(4H, t, Jvic=6.2 Hz, OCH2CH2CH2) & 1.33 (4H, quintet, Jvic= 3.7 Hz, OCH2CH2CH2).

The former protons were found slightly upfield as compared to similar hydrogen in

3.64 (δ 4.05) & 3.65 (δ 3.84); obviously due to the +I effect of the extra methylene

group present in 3.66. In the aromatic region, characteristic doublets of H-3 & H-2

were centered at δ 7.59 (2H, Jtrans=15.9 Hz) and 7.39 (2H, Jtrans=15.9 Hz) respectively.

The remaining protons belonging to the C-1 phenyl (H-3’, 4’, 5’ & 6’) and C-3 phenyl

(H-2’’, 3’’, 4’’, 5’’ & 6’’) rings were found to be placed at the expected δ and J values

in the aromatic region (vide experimental).

ESI-MS spectrum of 3.66 had (M+Na) ion at m/z 553 (100%) along with other ions at

m/z 159 (38%), 158 (7%), 102 (40%), 76 (32%) and its mass fragmentation pattern

was found to be similar as shown in Chart-1 (vide experimental).

The gross structure of 3.66 has been further supported by its 13C-NMR (100 MHz,

CDCl3). The downfield resonances placed at δ 192.60 and 157.61 could be given by

C=O and C-2’ respectively while the double bond carbon atoms C-3 and C-2 were

resonating at δ 142.65 and 112.64 respectively. The internal chain carbon atoms

generated three signals at δ 68.29 (OCH2CH2CH2), 29.20 (OCH2CH2CH2) and 25.90

(OCH2CH2CH2). The aromatic rings carbon atoms C-1’, 3’, 4’, 5’, 6’ and C-1’’, 2’’,

3’’, 4’’, 5’’, 6’’ were also found to be placed at the appropriate positions in the

aromatic region (vide experimental).


The compound 3.72 (79%, m.p. 150-152oC) was obtained (Scheme-3.19) from the

reaction of 3.66 with phenyl hydrazine under the same conditions as described above

for 3.70.

146

1'

3'

4'

5'

6'

2'

12

3

1''

2'' 3''

4''

5''6''

3''

4''

5''

6''

2''1''

12

3 4

5

5'''3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)4 CH2 O

NN

HX

HMHA

HM

HA

HX


3.66

O CH2 (CH2)4 CH2 O

O O

3.72

Scheme-3.19

The expected bands in the IR spectrum of 3.72 were obsereved at 1596 (C=N), 2934,

2878 (methylene stretch) and 1236, 1025 (C-O). Its 1H-NMR spectrum was highly

amenable to its interpretation and was similar to those of 3.70 & 3.71. At the lowest

downfield, a two hydrogens doublet of doublet at δ 7.89 (Jm,o=1.7, 7.4 Hz) could be

furnished by H-6’ due to its vicinity to the pyrazoline ring atom (N-2). Three doublet

of doublets centered at δ 5.09 (2H, JXM=12.1 Hz, JXA=7.0 Hz), 3.72

(2H, JMA=17.3 Hz, JMX=12.1 Hz) & 3.23 (2H, JAX=7.0 Hz, JAM=17.3 Hz) were

assigned to H-X, H-M and H-A respectively. In a double irradiation technique,

irradiation of doublet of doublet at δ 5.09 (H-X) converted the doublet of doublets at

δ 3.72 (H-M) and 3.23 (H-A) to doublet each which certainly describes that H-X,

H-M & H-A are intercoupling among each other.

The protons belonging to N-1, C-3 and C-5 phenyl rings were resonating at the

similar positions as described in 3.70 & 3.71 (vide experimental). The signals placed

at δ 3.68 (4H, m), 1.60 (4H, t, Jvic=6.4 Hz) and 1.32 (4H, quintet, Jvic=2.8 Hz) were

easily allotted to internal chain OCH2CH2CH2, OCH2CH2CH2 and OCH2CH2CH2

group respectively.

13C-NMR spectrum of 3.72 showed recognizable resonances at δ 156.93, 146.72,

146.75, 64.48 and 46.89 which were represented by C-2’, C-1’’’, C-3, C-5 and C-4

respectively. The carbon atom of the internal spacer produced three signals at δ 68.27

147

(OCH2CH2CH2), 29.28 (OCH2CH2CH2) and 25.79 (OCH2CH2CH2). The carbon

atoms of the three phenyl rings present at N-1, C-3 & C-5 were found to be resonating

at the expected δ values in the aromatic region (vide experimental).

The appearance of ions in the ESI-MS spectrum of 3.72 at m/z 733 (M+Na, 32%),

709 (18%), 707 (27%), 620 (48%), 619 (78%), 618 (54%), 617 (60%), 601 (38%) and

536 (10%) also confirmed the proposed expression and its mass fragmentation pattern


Synthesis of bischalcones 3.67-3.69

The compounds 3.67-3.69 were prepared in good yields from the O-alkylation of

chalcone 3.63 with suitable 1,ω-dibromoalkane (1,8-dibromooctane,

1,10-dibromodecane & 1,12-dibromododecane respectively) under the similar

conditions as described earlier for 3.64-3.66. The characteristics spectral data of

3.67-3.69 have been presented in Table-1 (vide experimental).

1'

3'

4'

5'

6'

2'O CH2 (CH2)n CH2 O

O O

12

3

1''

2'' 3''

4''

5''6''

3.67 (n=6), 3.68 (n=8), 3.69 (n=10)

Synthesis of bispyrazolines 3.73-3.75

The compounds 3.73-3.75 were prepared from the cyclization reaction of the

bischalcones 3.67-3.69 with phenyl hydrazine under the similar conditions as

described earlier for 3.70. The physical and characteristics spectral data of 3.73-3.75

have been given in Table-2.

3''

4''5''

6''

2''1''

12

3 4

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)n CH2 O

NN

HX

HMHA

HM

HA

HX

3.73 (n=6), 3.74 (n=8), 3.75 (n=10)

148

Table-1: Physical and characteristics spectral data of bischalcones 3.67-3.69

Jtrans= 15.9-15.7 Hz

Table-2: Physical and characteristics spectral data of bispyrazolines 3.73-3.75

*JXA= 7.2-7.0 Hz , JXM= 12.2-12.1 Hz , JMA= 17.8-17.2 Hz

To generalize the above described cyclization reaction of bischalcones, these

investigations have also been extended upon the synthesis of tolyl substituted

bispyrazolines 3.83-3.88.

3''

4''

5''

6''

2''1''1

23 4

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'6' N

N

O CH2 (CH2)n CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.83-3.88

n= 2, 3, 4, 6, 8, 10

Compd. m.p. (°C)

Yield (%)

IR (υmaxcm-1)

1H-NMR (δ )

13C-NMR (δ ) ESI-MS (m/z)

C=O C=C H-2* H-3* C=O C-3 C-2

3.67

70-72

71 1656

1598

7.35 (d)

7.54 (d)

192.89 142.42 112.38 559 (M+1)+

3.68

58-60 76

1665

1602

7.36 (d)

7.55 (d)

190.96 142.70 112.61 609 (M+Na)+

3.69

64-66 72 1655 1600 7.11 (d)

7.39 (d)

192.98 142.74 112.62 614 (M)+

Compd. m.p (°C)

Yield (%)

IR (υmax cm-1)

1H-NMR (δ) 13C-NMR (δ) ESI-MS (m/z)

C=N H-X* H-M* H-A* C=N C-5 C-4

3.73 165-167

75 1596 5.18 (dd)

3.93 (dd)

3.31 (dd)

147.98 64.55 46.91 738 (M)+

3.74 110-112

68 1594 5.25 (dd)

4.13 (dd)

3.35 (dd)

146.91 63.31 45.75 766 (M)+

3.75 125-127

65 1599 5.12 (dd)

4.00 (dd)

3.30 (dd)

147.89 64.34 44.35 795 (M+1)+

149

The bisheterocyclics 3.83-3.88 needed for this study were synthesized starting from

chalcone 3.76 which was obtained from the Clasien-Schmidt reaction of

o-hydroxyacetophenone with tolualdehyde (Scheme-3.20). The decomposition of the

reaction mixture into iced HCl provided a crude substance that was crystallized from

MeOH to yield pure compound 3.76 (80%, m.p. 102-104oC).

OH

O

CH3+ NaOH/ EtOH/ O0C

12

31'

2'3'

4'

5'

6'

CH3

CH3

O

OH

O

CH3

1''

2''

3''

4''

5''

6''

3.76

Scheme-3.20

IR spectrum of 3.76 had three major absorptions at 3217 (O-H), 1690 (C=O) and

1600 (C=C) cm-1. In its 1H-NMR spectrum (400 MHz, CDCl3), the lowest downfield

resonance was placed at δ 12.87 (1H, OH) that was exchangeable with D2O. The

double bond protons H-3 and H-2 were very well resonating at δ 7.89 (1H, d,

Jtrans=15.4 Hz, H-3) and 7.62 (1H, d, Jtrans=15.4 Hz, H-2) respectively. The aromatic

ring hydrogens were centered at δ 7.57 (2H, d, Jo=8.0 Hz, H-2’’, 6’’), 7.50 (1H, td,

Jm,o=1.6, 8.4 Hz, H-4’), 7.24 (2H, d, Jo=8.0 Hz, H-3’’, 5’’), 7.03 (1H, dd, Jp,o=1.0,

8.4 Hz, H-5’) and 6.94 (1H, td, Jp,o=1.1, 8.0 Hz, H-3’). In the aliphatic region, a sharp

singlet integrating for three hydrogens at δ 2.40 was assignable to 4’’-CH3 group. The

structure of 3.76 was also confirmed from its GC-MS spectrum which exhibited the

molecular ion at m/z 238 (60%).

(i). Synthesis of bispyrazolines 3.83

The compound 3.83 was prepared in two steps:

Synthesis of bischalcone 3.77

The chalcone 3.76 was reacted with 1,4-dibromobutane in the presence of anhydrous

K2CO3 and tetrabutyl ammonium iodide (PTC) in dry acetone (Scheme-3.21). The

decomposition of reaction mixture into iced HCl provided a crude product that was

crystallized from MeOH to yield pure compound 3.77 (68%, m.p. 143-145oC).

150

OH

O

CH3

12

3

2''3''

5''6''6'

5'

4'

3'4''

K2CO3/acetone/ Br-(CH 2)4-Br/Bu4N+I-/ ∆

12

31'

2'3'4'

5'6'

1''2'' 3''

4''

5''6''

CH3

O CH2 (CH2)2

O

CH2 O

O

CH3

3.77

Scheme-3.21

The presence of enone moiety and ether linkage was confirmed by the appearance of

absorptions at 1656 (C=O), 1598 (C=C) and 1235, 1020 (C-O) in the IR spectrum of

3.77. Its 1H-NMR (400 MHz, CDCl3) spectrum showed a doublet of doublet at δ 7.62

(2H, Jm,o=2.2, 7.6 Hz) which may be allotted to H-6’. The C-1 & C-3 phenyl ring

hydrogens presented themselves as a six protons multiplet at δ 7.41, four protons

doublet at δ 7.12 (Jo=7.0 Hz), two protons triplet of doublet at δ 7.01 (Jp,o=0.6,

7.4 Hz) and two protons doublet at δ 6.82 (Jo=8.2 Hz) which could be assigned to

H-2’’, 6’’, 4’, H-3’’, 5’’, H-5’ and H-3’ respectively. The olefinic protons H-3 and

H-2 were placed at δ 7.54 (2H, d) and 7.29 (2H, d) respectively and the coupling

value of Jtrans=15.9 Hz between these hydrogens describes their trans relationship. A

singlet integrating for six protons at δ 2.31 could be very well ascribed to CH3 group.

The protons of the internal chain as expected showed two signals at δ 3.89 (4H, t,

Jvic=6.2 Hz, OCH2) and 1.88 (4H, quintet, Jvic=6.2 Hz, OCH2CH2). The UV-Vis

spectrum of 3.77 furnished two maxima at 330 and 209 due to n→π* and π→π*

transitions respectively.

A look at 13C-NMR spectrum of 3.77 revealed that resonances due to enone moiety

were located at δ 192.96 (C=O), 142.66 (C-3) & 120.72 (C-2) while C-2’ directly

bonded to oxygen atom also appeared downfield at δ 157.44. The carbon atoms

belonging to the tolyl ring were present at δ 140.68 (C-4’’), 132.33 (C-1’’), 129.63

(C-2’’, 6’’) and 126.49 (C-3’’, 5’’). The remaining aromatic carbon atoms C-1’, C-6’,

C-4’, C-5’ & C-3’ were found to be placed at δ 132.79, 130.40, 129.43, 128.32 &

112.25 respectively. The aliphatic region was also occupied by three signals at

δ 67.78 (OCH2CH2), 26.10 (OCH2CH2) and 21.46 (CH3).

151

The ESI-MS spectrum of 3.77 also confirmed the proposed structure which exhibited

important ions at m/z 554 (M+Na+1, 10%), 553 (M+Na, 21%), 243 (50%), 242

(100%), 186 (9%) & 142 (6%). Its mass fragmentation pattern has been presented in

Chart-3. O CH2 (CH2)2 CH2 O

O O

CH3 CH3

m/z 530

m/z 242 (100%)

m/z 243 (50%)

m/z 186 (9% )

m/z 142 (6%)

m/z 553 (M+Na, 21%)

m/z 554 (M+Na+1, 10%)

O CH2 (CH2)2 CH2 O

O O

C C CH OC

-C20O2H16

-C4H8

-C6H12O

...... ......

+

+

+

.

.

a a

Chart-3


The compound 3.77 was refluxed with phenyl hydrazine in EtOH/AcOH solution

(Scheme-3.22) and cooling of the resulting reaction mixture in an ice bath provided a

solid substance. The resulting product was crystallized from MeOH to yield pure

compound 3.83 (68%, m.p. 232-234oC).

1'

3'

4'

5'

6'


O O

CH3CH312

3

1''

2'' 3''

4''

5''6''

3''

4''

5''

6''

2''1''

12

34

5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)2 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3


3.77

3.83

Scheme-3.22

152

IR spectrum of 3.83 exhibited significant bands at 1598 (C=N), 2920, 2868

(methylene C-H) & 1232, 1018 (C-O) cm-1. In the aromatic region of its 1H-NMR

(400 MHz, CDCl3) spectrum, major signals were centred at δ 7.92 (2H, dd, Jp,o=1.2,

7.8 Hz), 7.29 (6H, m), 7.15 (4H, td, Jm,o=2.1, 7.6 Hz) and 7.05 (4H, dd, Jp,o=1.1, 9.0

Hz) which were belonging to H-6’, H-4’, 3’’’, 5’’’, H-2’’, 6’’ and H-2’’’, 6’’’

respectively. The protons H-5’, H-3’ and H-3’’, 5’’ were resonating at δ 6.96 (2H, td,

Jp,o=1.1, 7.8 Hz), 6.86 (2H, d, Jo=7.8 Hz) and 6.80 (4H, td, Jm,o=2.5, 7.8 Hz)

respectively while H-4’’’ resonated at δ 6.72 as a two proton doublet of triplet

(Jm,o=2.2, 8.0 Hz).

Three doublet of doublets present at δ 5.10 (2H, JXM=12.1 Hz, JXA=7.0 Hz), 3.89

(2H, JMX=12.1 Hz, JMA=17.2 Hz) and 3.24 (2H, JAX= 7.0 Hz, JAM=17.2 Hz) could be

assigned to pyrazoline ring protons H-X, H-M & H-A respectively. Rest of the

spectrum had a triplet at δ 3.94 (4H, t, OCH2), a singlet at δ 2.23 (6H, CH3) and a

quintet at δ 1.82 (OCH2CH2). The UV-Vis spectrum of 3.83 showed two maxima at

355 and 263 nm which may be ascribed to n→π* and π→π* transitions respectively.

The carbon framework of the compound 3.83 was confirmed from its 13C-NMR

(100 MHz, CDCl3) spectrum which displayed the signals of pyrazoline ring at

δ 146.76 (C-3), 65.87 (C-5) and 45.98 (C-4). The most downfield signal at δ 156.86

was easily attributed to C-2’ due to its direct linkage to the oxygen atom. The

resonances placed at δ 145.14, 145.12 and 139.99 could be provided by C-1’’’, C-1’’

and C-4’’ respectively. The remaining aromatic carbon atoms produced their signals

in the range of δ 137.05-118.75. The upfield appearance of C-3’ at δ 113.30 and

C-2’’’, 6’’’ at δ 112.25 certainly occurred due to the electron releasing effect of

C-2’ alkoxy group and CH3 group present at C-4’’ respectively. In addition to two

signals at δ 67.97 (OCH2) and 26.28 (OCH2CH2) in the aliphatic region, there also

appeared a resonance at δ 21.20 due to CH3 group. The ESI-MS spectrum of 3.83 had

(M+Na+1) and (M+Na) ions at m/z 734 (49%) and 733 (100%) respectively and its

mass fragmentation pattern has been shown in Chart-4.




The chalcone 3.76 was reacted with 1,5-dibromopentane (Scheme-3.23) under the


(60%, m.p. 76-78oC).

153

OH

O

CH3


1 2

3

1'

2'3'4'

5'

6'1''

2'' 3''

4''

5''6''

O CH2 (CH2)3

O

CH2 O

O

CH3CH3

5'

4'

3'

6'

2'

1'1

2

3

1''

2''3''

4''

5''

6''

3.76

3.78

Scheme-3.23

IR spectrum of 3.78 showed strong absorptions at 1654 and 1599 cm-1 due to C=O

and C=C groups respectively and the additional bands were also observed at 2938,

2863 (methylene C-H) and 1237, 1024 (C-O) cm-1. Its 1H-NMR (400MHz, CDCl3)

spectrum was very helpful to acertain the trans geometry around C-2 & C-3 double

bond which showed two doublets at δ 7.60 (2H, H-3) & 7.36 (2H, H-2) having

coupling value of 15.8 Hz. Due to the effect the C=O group, H-6’ was resonating at

δ 7.62 as a doublet of doublet (2H, Jm,o=1.8, 7.6 Hz). The p-disubstituted benzene ring

hydrogens generated a multiplet at δ 7.42 (6H, H-2’’, 4’, 6’’) and a doublet

(Jo=7.2 Hz) at δ 7.20 (4H, H-3’’, 5’’). The aromatic hydrogens H-5’ & H-3’ were

placed at δ 7.01 (2H, td, Jp,o=0.7, 7.4 Hz) and 6.94 (2H, d, Jo=8.4 Hz) respectively.

Four signals were also centered in the aliphatic region at δ 4.03 (4H, t, Jvic=6.4 Hz,

OCH2), 2.37 (6H, s, CH3), 1.78 (4H, m, OCH2CH2) and 1.51 (2H, m, OCH2CH2CH2). 13C-NMR (100MHz, CDCl3) of 3.78 showed the downfield resonances at δ 192.92,

157.53, 142.64, 129.66 & 120.75 may be assigned to C=O, C-2’, C-3, C-2’’, 6’’ &

C-2. The internal chain methylene groups produced three signals at δ 67.74

(OCH2CH2CH2), 29.06 (OCH2CH2CH2) and 25.80 (OCH2CH2CH2). The carbon

atoms belonging to the phenyl ring (C-3’, 4’, 5’, 6’ & C-1’’, 2’’, 3’’, 4’’, 5’’, 6’’)

were also found to be resonating at the appropriate places in the aromatic region

(vide experimental).

154

NN

O CH2 (CH2)2 CH2 O

NN

CH3 CH3

H

H

H

H

H

H

NN

O CH2 (CH2)2 CH2 O

CH3

N

CH3

H

H

H

NN

O CH2 (CH2)2 CH2 O

CH3CH3

H

NN

O CH2 (CH2)2 CH2 O

CH3

H

NN

O CH2 (CH2)2 CH2 O

NN

CH3H

H

H

H

O CH CH (CH2)2

NN

CH3

H

H

H

O CH CH

NN

CH3

H

H

H

O CH CH

NN

CH3

H

H

H

H

O C C

NN

CH3

H

+

+

+

+

NN

O CH2 CH2 CH2 O

NN

CH3 CH3H

H

H

H

H

H

H

NN

O CH2 CH CH O

NN

H H H

O CH2

NN

H

NN

O

O CH2

N NN

O

+

+

+

m/z 710-C6H8N

m/z 616 (10%)

-N

m/z 602 (9%)

m/z 473 (8%)

m/z 541 (21%)

-C13H13

m/z 381 (92%)

m/z 353 (99%)

m/z 354 (18%)

m/z 349 (15%)

+H.

-C2H4

-H2, -H

m/z 543 (12%)

-C13H11

-C2H10

m/z 509 (13%)

m/z 483 (11%)

-C2H2

m/z 469 (5%)

-N

m/z 734 (M+Na+1, 49%)m/z 733 (M+Na, 100%)

+

......

+

+

.....

.

+.

+

+

Chart-4


The compound 3.84 (65%, m.p. 140-142oC) was prepared from the reaction of

bischalcone 3.78 with phenyl hydrazine (Scheme-3.24) under the similar conditions

as used earlier for 3.83.

155

1'

3'

4'

5'

6'


O O

CH3CH312

3

1''

2'' 3''

4''

5''6''

3''

4''

5''

6''

2''1''1

2

3 4

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)3 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3


3.78

3.84

Scheme-3.24

In the IR spectrum of 3.84, noticeable band was observed at 1596 due to the presence

of C=N moiety. A detailed analysis of its 1H-NMR (400 MHz, CDCl3) spectrum fully

lent support to the proposed structure. At the most downfield, a doublet of doublet

present at δ 7.88 (Jp,o=1.0, 7.8 Hz) could be assigned to H-6’. The pyrazoline ring

protons H-X, H-M & H-A furnished three resonances at δ 5.11 (2H, dd, JXM=12.1 Hz,

JXA=7.0 Hz), 3.78 (2H, dd, JMX=12.1 Hz, JMA=17.3 Hz) & 3.23 (2H, dd, JAX=7.0 Hz,

JAM=17.3 Hz). The phenyl ring protons H-3’, 4’, 5’, 6’, H-2’’, 3’’, 5’’, 6’’ and H-2’’’,

3’’’, 4’’’, 5’’’, 6’’’ were also resonating at the suitable δ and J values in the aromatic

region (vide experimental).

In the 100 MHz 13C-NMR (CDCl3) spectrum of 3.84, C-2’, C-1’’’ and C-4’’ were

found to be placed at δ 156.84, 145.11 and 139.98 respectively. The methylene groups

of the intervening chain were resonating at δ 67.99 (OCH2CH2CH2), 29.10

(OCH2CH2CH2) and 28.51 (OCH2CH2CH2). The pyrazoline ring carbon atoms C-3,

C-4 & C-5 provided three signals at δ 146.72, 46.27 & 64.23 respectively. The carbon

atoms of the three phenyl rings (N-1, C-3 & C-5) were found at the usual positions in

the aromatic region (vide experimental).

The ESI-MS spectrum of 3.84 also corroborated its structure which exhibited the

(M+1) ion at m/z 725 (78%) and its mass fragmentation pattern was found to be

similar as shown in Chart-4 (vide experimental).

156



chalcone 3.76 with suitable 1,ω-dibromoalkane (1,6-dibromohexane,

1,8-dibromooctane, 1,10-dibromodecane & 1,12-dibromododecane respectively)

under the similar conditions as described earlier for 3.77-3.78. The major spectral data

of 3.79-3.82 have been presented in Table-3 (Plate-25-28 & vide experimental).

1'

3'

4'

5'6'

2'

O CH2 (CH2)n CH2 O

O O

CH3 CH312

3

1''

2'' 3''

4''

5''6''

3.79 (n=4), 3.80 (n=6), 3.81 (n=8), 3.82 (n=10)


The compounds 3.85-3.88 were obtained from the reaction of 3.79-3.82 with phenyl

hydrazine under the similar condition as described earlier for 3.83. The physical and

characteristics spectral data of 3.85-3.88 have been provided in Table-4

(Plate-29-32).

3''

4''

5''6''

2''1''1

2

3 4

5

5''' 3'''2'''

6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)n CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.85 (n=4), 3.86 (n=6), 3.87 (n=8), 3.88 (n=10)

157


*Jtrans=15.9-15.7 Hz


*JXA= 7.1-7.0 Hz , JXM= 12.1-12.0 Hz , JMA= 17.3-17.2 Hz

Mechanistic consideration

The cyclization reactions described above i.e. 3.64-3.69 & 3.77-3.82→3.70-3.75 &

3.83-3.88 can be visualized as having occurred through an initial attack (path a) of

phenyl hydrazine upon the carbonyl group of enone moiety under the influence of

protons followed by dehydration to produce 3.64’-3.69’ & 3.77’-3.82’. The later

further undergo cyclization with the addition of proton to give 3.70-3.75 & 3.83-3.88

as end product (Scheme-3.24a). In other way, phenyl hydrazine can also undergo

addition upon the enone part of 3.64-3.69 in the Michael fashion (path b) to give

Compd.

m.p. (°C)

Yield (%)

IR (υmaxcm-1)

1H-NMR (δ )

13C-NMR (δ )

ESI-MS (m/z)

C=O C=C H-3* H-2* C=O C-3 C-2

3.79 102-104

70 1652 1600 7.60 (d)

7.37 (d)

192.95 142.62 120.67 559 (M+1)+

3.80 110-112

73 1654 1593 7.57 (d)

7.36 (d)

192.99 142.66 120.66 587 (M+1)+

3.81 120-122

75 1659 1599 7.60 (d)

7.41 (d)

192.96 142.64 120.63 615 (M+1)+

3.82

93-95

80 1653 1599 7.43 (d)

7.17 (d)

192.97 142.67 120.64 665 (M+Na)+

Comp

d.

m.p (°C)

Yield (%)

IR (υmax cm-1)

1H-NMR (δ) 13C-NMR(δ)

ESI-MS (m/z)


3.85 80-

82

75 1598 5.10 (dd)

3.65 (dd)

3.33 (dd)

146.73 63.48 46.84 761 (M+Na)+

3.86 148-150

70 1596 5.16 (dd)

3.73 (dd)

3.04 (dd)

147.90 63.31 45.88 789 (M+Na)+

3.87 98-100

60 1596

5.17 (dd)

4.08 (dd)

3.30 (dd)

147.95 64.36 46.93 795 (M+1)+

3.88 120-122

61 1594

5.19 (dd)

4.05 (dd)

3.32 (dd)

147.97 64.38 46.81 823 (M+1)+

158

3.70’-3.75’ & 3.83’-3.88’ as the intermediate which subsequently undergo cyclization

followed by dehydration to give 3.70”-3.75” & 3.83”-3.88” (Scheme-3.24a).

But inspite of our repeated and best efforts, we were not able to isolate any product

similar to 3.70’-3.75’ & 3.83’-3.88’. Thus, in bischalcones 3.64-3.69 & 3.77-3.82,

direct condensation of phenyl hydrazine with carbonyl group (path a) is preferred

over the Michael addition (path b, Scheme-3.24a).

NH2 NH Ar

O CH2(CH2)n

N NH

Ar

H

R

..

-}

-}H+

H+

ba

path b

..

-H2O

cyclisation

O

OH NH

HN

Ar

CH2(CH2)n

R

-} -}

O CH2(CH2)n

N NH

Ar

R

O CH2(CH2)n

NN

HH

H

Ar

R

..

-}-}O CH2(CH2)n

OH

NH NH

Ar

R

path a

H+

-H2O

3.64'-3.69' (R=H) & 3.77'-3.82' (R=CH3)

H+

-H+

3.70-3.75 (R=H)

(n = 2, 3, 4, 6, 8, 10)

-}

Ar = R

3.83-3.88 (R=CH3)

3.64-3.69 (R=H)

3.77-3.82 (R=CH3)

3.70'-3.75' (R=H)

3.83'-3.88' (R=CH 3)

cyclisation

3.70''-3.75'' (R=H)

3.83''-3.88'' (R=CH 3)

O

O CH2 (CH2)n

R

O CH2(CH2)n

N NH

OH

Ar

HH

R

, R = H, CH3

/+H.

Scheme-3.24a

Antimicrobial evaluations of bischalcones (3.64-3.69 & 3.77-3.82) &

bispyrazolines (3.70-3.75 & 3.83-3.88)

The in vitro antibacterial and antifungal activities of the prepared compounds

(3.64-3.69, 3.70-3.75, 3.77-3.82 & 3.83-3.88) were determined against five bacterial

strains viz. Klubsellia pneumoniae (MTCC 3384), Pseudomonas aeruginosa (MTCC

424), Escherichia coli (MTCC 443), Staphylococcus aureus (MTCC 96), Bacillius

subtilis (MTCC 441) and four fungi strains viz. Aspergillius janus (MTCC 2751),

Aspergillius niger (MTCC 281), Aspergillius flavus (MTCC 277) & Pencillium

glabrum (MTCC 4951). The zone of inhibition71 and MIC72 of these compounds were

159

analyzed by using paper disc diffusion method and serial tube dilution method

respectively. These analyses were carried out by following the similar procedures

which are described on page no. 43,44 (Chapter-IIa) . Amoxicillin and Fluconazole

were used as reference drugs for antibacterial and antifungal examinations

respectively. The zone of inhibitions (mm) has been recorded as the average diameters

which are given in Table-5 & Table-7 (Fig.-1 & Fig.-3) and MIC values are

presented in Table-6 & Table-8 (Fig.-2 & Fig.-4).

Table-5 describes that compounds 3.68, 3.69, 3.81 & 3.82 were found to exhibit zone

of inhibition of 11 mm against Pseudomonas aeruginosa while the zone of inhibition

of 13 mm was provided by the compound 3.69 & 3.82 against the strain Klubsellia

pneumoniae. The compounds 3.66 & 3.79 showed the zone of inhibition of 11 mm

against Staphylococcus aureus. The compounds 3.64-3.69 and 3.77-3.82 provided

moderate activity against the above given fungi strains at the zone of inhibition of

6-10 mm.

Table-6 describes that compound 3.69 showed significant activity (MIC-4 µg/ml)

against the strain Aspergillius janus and the compounds 3.77, 3.79, 3.80 & 3.81

displayed similar activity against the stain Pseudomonas aeruginosa. The growth of

strain Bacillius subtilis was inhibited by the compounds 3.79, 3.80 & 3.81 at MIC of

4 µg/ml. The compound 3.80 displayed similar activity against the strain Aspergillius

niger while the compound 3.81 largely inhibited the growth of two fungi strains

Aspergillius janus and Aspergillius niger (MIC-4 µg/ml). The remaining compounds

exhibited noticeable MIC (8-16 µg/ml) against the tested microorganisms.

It is clear from the Table-7 that the bispyrazolines 3.71 & 3.84 inhibited the growth

of bacteria strain Pseudomonas aeruginosa and Klubsellia pneumoniae at zone of

inhibition of 11 & 12 mm respectively and the compounds 3.74 & 3.87 showed the

zone of inhibition of 11 mm against Klubsellia pneumoniae. The compounds 3.75 &

3.88 also had similar activity against Aspergillius flavus.

Table-8 describes that the compounds 3.70 & 3.83 were found to be highly active

against Klubsellia pneumoniae and Bacillius subtilis (MIC-8 µg/ml) while the rest of

compounds showed MIC of 8-16 µg/ml against the tested microorganisms.

160

Table-5. In vitro zone of inhibitions (mm) of bischalcones 3.64-3.69 & 3.77-3.82

Compound Gram (-ve) bacteria Gram (+ve) bacteria Fungi

Escherichia

coli

Pseudomonas

aeruginosa

Klubssila

pneumoniae

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

Aspergillius

flavus

3.64 -- -- 7 8 -- 8 9 -- 7

3.65 -- 8 7 6 -- 6 7 6 8

3.66 6 7 9 11 6 10 8 6 8

3.67 7 -- 8 9 7 -- 6 8 --

3.68 9 11 8 8 9 7 6 8 --

3.69 8 11 13 9 7 7 10 -- 9

3.77 -- -- 7 -- -- 8 9 -- 7

3.78 -- 8 7 10 -- 6 7 6 8

3.79 6 7 9 11 6 10 8 6 8

3.80 7 -- 8 9 7 -- 6 8 --

3.81 9 11 8 6 9 7 6 8 --

3.82 8 11 13 7 7 7 10 -- 9

Amoxicillin 18 25 19 20 23 -- -- -- --

Fluconazole -- --

-- -- -- 22 26 22 23

161

Table-6. In vitro MIC (µg/ml) of bischalcones 3.64-3.69 & 3.77-3.82

Compd. Gram (-ve) bacteria Gram (+ve) bacteria Fungi

Escherichia

coli

Klubssila

pneumoniae

Pseudomonas

aeruginosa

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

Aspergillius

flavus

3.64 16 16 16 16 16 16 16 8 8

3.65 16 16 16 8 16 16 16 8 8

3.66 16 8 16 16 8 8 16 8 16

3.67 8 8 16 16 8 16 16 16 16

3.68 8 16 8 16 16 8 8 16 16

3.69 8 8 8 16 16 4 16 8 16

3.77 16 8 4 8 8 16 8 8 16

3.78 16 8 16 16 8 16 16 8 16

3.79 16 8 4 8 4 16 16 8 8

3.80 8 8 4 8 4 8 16 4 16

3.81 16 8 4 8 4 16 16 4 4

3.82 16 8 8 8 8 16 16 16 16

Amoxicillin 2 2 2 2 2 -- -- -- --

Fluconazole -- -- -- -- -- 1 1 1 1

162

Table-7. In vitro zone of inhibitions (mm) of bispyrazolines 3.70-3.75 & 3.83-3.88

Gram (-ve) bacteria Gram (+ve) bacteria Fungi

Compound

Escherichia

coli

Pseudomonas

aeruginosa

Klubssila

pneumoniae

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

Aspergillius

flavus

3.70 -- 9 8 8 -- 9 10 -- 9

3.71 -- 11 12 6 7 7 9 7 --

3.72 6 7 -- 7 6 -- 9 8 --

3.73 7 -- 8 7 6 6 7 8 10

3.74 -- 8 11 10 -- 6 8 10 10

3.75 8 -- -- 6 7 8 -- 10 11

3.83 -- 9 8 -- -- 9 10 -- 9

3.84 -- 11 12 9 7 7 9 7 --

3.85 6 7 -- 10 6 -- 9 8 --

3.86 7 -- 8 9 6 6 7 8 10

3.87 -- 8 11 8 -- 6 8 10 10

3.88 8 -- -- 8 7 8 -- 10 11

Amoxicillin 18 25 19 20 23 -- -- -- --

Fluconazole -- -- -- -- --

22 26 22 23

163

Table-8. In vitro MIC (µg/ml) of bispyrazolines 3.70-3.75 & 3.83-3.88


Compound Escherichia

coli

Klubssila

pneumoniae

Pseudomonas

aeruginosa

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

Aspergillius

flavus

3.70 8 4 16 16 16 8 8 8 16

3.71 16 8 8 16 16 8 16 8 8

3.72 8 8 16 8 8 8 8 8 8

3.73 8 8 8 16 8 8 16 8 16

3.74 8 8 16 16 16 8 16 16 16

3.75 16 8 16 16 16 8 8 16 16

3.83 16 8 8 8 4 16 16 16 16

3.84 16 16 8 16 16 16 8 16 8

3.85 16 16 16 16 16 16 8 8 8

3.86 16 16 8 16 16 8 8 8 8

3.87 16 8 16 8 16 16 16 16 16

3.88 8 16 16 16 16 16 16 16 16

Amoxicillin 2 2 2 2 2 -- -- -- --

Fluconazole -- -- -- -- -- 1 1 1 1

164

Figure-1. In vitro zone of inhibitions (mm) of bischalcones 3.64-3.69 & 3.77-3.82

Figure-2. In vitro MIC ( µg/ml) of bischalcones 3.64-3.69 & 3.77-3.82

Figure-3. In vitro zone of inhibitions (mm) of bispyrazolines 3.70-3.75 & 3.83-3.88

165

Figure-4. In vitro MIC ( µg/ml) of bispyrazolines 3.70-3.75 & 3.83-3.88

It is evident from the above zone of inhibition and MIC data that bischalcones and

bispyrazolines linked through the internal chain of four, six, eight and ten carbon atoms

exhibited significant activity.

It may be concluded that this study describes the general and efficient method for the

synthesis of new series of bispyrazolines linked via the 3-aryl ring under the normal

conditions. The significant antimicrobial activities were provided by the bischalcones and

bispyrazolines built around internal spacer consisting of the even number of methylene

groups. The compounds involving longer internal chain seems to be better antimicrobial

products. The importance of this work lies in the possibility that the new compounds

might be more efficacious derivatives against the tested strains for which through

investigations regarding their toxicity and biological studies could be helpful in designing

the potential antimicrobial agents.

166

Experimental

Synthesis of (E)-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one 3.63

A solution of o-hydroxyacetophenone (5.0 ml, 0.0070 mol), benzaldehyde (5.0 ml,

0.0070 mol) and NaOH (5.0 g, 0.024 mol) in EtOH (25.0 ml) was stirred in an ice

bath for 10 hrs. During the course of reaction, the initially formed creamish mixture

changed to a reddish gummy mass. The resulting mass was poured into iced-HCl to

provide a crude substance which was crystallized from CH3OH to yield a pure

compound 3.63.

O

OH3'

4'

5'

6'

1'

2'

12

3

1''

2''

3''

4''

5''

6''

3.63

3.63: Yellow needles, Yield 82%; m.p.: 55-57oC. UV-Vis (MeOH) λmax(nm): 330,

233; IR (KBr) cm-1: 3216 (O-H), 1695 (C=O), 1604 (C=C); 1H-NMR (400 MHz,

CDCl3): δ 12.81 (1H, s, OH), 7.94 (1H, dd, Jp,o=1.0, 8.4 Hz, H-6’), 7.91 (1H, d,

Jtrans=15.5 Hz, H-3), 7.68 (2H, dt, J=1.0, 2.8, 4.4 Hz, H-2’’, 6’’), 7.65 (1H, d,

Jtrans=15.5 Hz, H-2), 7.51 (1H, td, Jm,o=1.6, 7.2 Hz, H-4’), 7.44 (3H, m, H-3’’, 4’’,

5’’), 7.04 (1H, dd, Jp,o=1.0, 8.4 Hz, H-5’), 6.95 (1H, td, Jp,o=1.1, 8.1 Hz, H-3’);

GC-MS: m/z (M)+ 224 (68%). Anal. Calc. for C15O2H12: Calc. C, 80.35 %; H, 5.36 %;

Found: C, 80.43 %; H, 5.32 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(butane-1,4-diylbis(oxy))bis(2,1-

phenylene))bis(3-phenylprop-2-en-1-one) 3.64

A suspension of chalcone 3.63 (2.0 g, 0.00840 mol), K2CO3 (2.0 g),

1,4-dibromobutane (0.90754 g, 0.00420168 mol) and tetrabutyl ammonium iodide

(1.0 g) in dry acetone (25 ml) was refluxed for 6 hrs with continuous stirring. The

progress of reaction was monitored by TLC. After the completion of reaction, the

reaction mixture turned into a colourless mass which was poured over iced-HCl to

provide crude solid which was crystallized from CH3OH:CHCl3 (3:1) to yield a pure

compound 3.64.

1'

3'

4'

5'

6'


O O

12

3

1''

2''3''

4''

5''6''

3.64

167

3.64: Yellow solid; Yield 69%; m.p.: 92-94oC. UV-Vis (MeOH) λmax(nm): 286, 229;

IR (KBr) cm-1: 2930, 2862 (methylene C-H), 1660 (C=O), 1596 (C=C), 1230, 1025

(C-O); 1H-NMR (400 MHz, CDCl3): δ 7.62 (2H, dd, Jm,o=1.7, 7.6 Hz, H-6’), 7.52

(2H, d, Jtrans=15.9 Hz, H-3), 7.50 (4H, m, H-2’’, 6’’), 7.42 (2H, ddd, Jp,m,o=1.0, 1.8,

7.4 Hz, H-4’), 7.34 (6H, m, H-3’’, 4’’, 5’’), 7.31 (2H, d, Jtrans=15.9 Hz, H-2), 7.02

(2H, td, Jp,o=0.7, 7.4 Hz, H-5’), 6.82 (2H, d, Jo=8.2 Hz, H-3’), 3.90 (4H, t,

Jvic=6.2 Hz, OCH2CH2), 1.88 (4H, t, Jvic=6.2 Hz, OCH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 192.80 (C=O), 157.50 (C-2’), 142.62 (C-3), 134.67 (C-4’’), 133.78 (C-1’),

132.34 (C-1’’), 129.40 (C-6’), 128.61 (C-2’’, 6’’), 128.24 (C-4’), 127.25 (C-5’),

120.51 (C-3’’, 5’’), 112.71 (C-2), 112.23 (C-3’), 67.70 (OCH2CH2), 26.04

(OCH2CH2); MS(ESI): m/z 525 (M+Na, 11%), 279 (70%), 223 (80%), 207 (42%),

147 (13%), 130 (76%), 93 (100%), 77 (23%). Anal. Calc. for C34O4H30: Calc.

C, 81.27 %; H, 5.97 %; Found: C, 81.32 %; H, 6.01 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(pentane-1,5-diylbis(oxy))bis(2,1-


The bischalcone 3.65 was prepared from the reaction of chalcone 3.63 (2.0 g, 0.00840

mol) with 1,5-dibromopentane (0.9661342 g, 0.0042016 mol) under the similar

conditions as used earlier for 3.64.

1'

3'

4'

5'

6'


O O

12

3

1''

2'' 3''

4''

5''6''

3.65




(2H, d, Jtrans=15.9 Hz, H-3), 7.50 (4H, dd, Jm,o=2.1, 7.6 Hz, H-2’’, 6’’), 7.40 (2H, ddd,

Jp,m,o=0.6, 1.8, 7.4 Hz, H-4’), 7.36 (2H, d, Jtrans=15.9 Hz, H-2), 7.28 (6H, m, H-3’’,

4’’, 5’’), 7.00 (2H, td, Jp,o=0.6, 7.6 Hz, H-5’), 6.82 (2H, d, Jo=8.2 Hz, H-3’), 3.84

(4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 1.50 (4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 1.30

(2H, quintet, Jvic=3.7 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 192.94

(C=O), 157.58 (C-2’), 142.67 (C-3), 134.89 (C-4’’), 133.60 (C-1’), 132.26 (C-1’’),

129.62 (C-6’), 128.70 (C-2’’, 6’’), 128.10 (C-4’), 127.24 (C-5’), 120.50 (C-3’’, 5’’),

168

112.72 (C-2), 112.20 (C-3’), 67.73 (OCH2CH2CH2), 29.00 (OCH2CH2CH2), 25.60

(CH2CH2CH2); MS(ESI): m/z 539 (M+Na, 14%), 145 (100%), 144 (29%), 102 (3%),

77 (17%). Anal. Calc. for C35O4H32: Calc. C, 81.39 %; H, 6.20 %; Found: C, 81.45 %;

H, 6.17 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(hexane-1,6-diylbis(oxy))bis(2,1-


The bischalcone 3.66 was obtained from the reaction of chalcone 3.63 (2.0 g,

0.00840 mol) with 1,6-dibromohexane (1.025 g, 0.00420168 mol) under the similar

conditions as described earlier for 3.64.

1'

3'

4'

5'

6'


O O

12

3

1''

2''3''

4''

5''6''

3.66




(2H, d, Jtrans=15.9 Hz, H-3), 7.51 (4H, dd, Jm,o=2.9, 7.6 Hz, H-2’’, 6’’), 7.43 (2H, ddd,

Jp,m,o=0.6, 1.8, 7.4 Hz, H-4’), 7.39 (2H, d, Jtrans=15.9 Hz, H-2), 7.32 (6H, m, H-3’’,

4’’, 5’’), 7.01 (2H, td, Jp,o=0.6, 7.6 Hz, H-5’), 6.89 (2H, d, Jo=8.2 Hz, H-3’), 3.78

(4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 1.58 (4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 1.33


(C=O), 157.61 (C-2’), 142.65 (C-3), 135.85 (C-1’), 135.72 (C-4’’), 132.40 (C-1’’),

129.53 (C-6’), 128.50 (C-2’’, 6’’), 128.22 (C-4’), 127.32 (C-5’), 120.31 (C-3’’, 5’’),

112.64 (C-2), 112.10 (C-3’), 68.29 (OCH2CH2CH2), 29.20 (OCH2CH2CH2), 25.90

(CH2CH2CH2); MS(ESI): m/z 553 (M+Na, 100%), 159 (38%), 158 (7%), 102 (40%),

76 (32%). Anal. Calc. for C36O4H34: Calc. C, 81.50 %; H, 6.41 %; Found: C, 81.46 %;

H, 6.44 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(octane-1,8-diylbis(oxy))bis(2,1-phenylene))bis(3-

phenylprop-2-en-1-one) 3.67


0.00840 mol) and 1,8-dibromooctane (1.142 g, 0.00420168) under the similar

conditions as used for 3.64.

169

1'

3'

4'

5'

6'


O O

12

3

1''

2''3''

4''

5''6''

3.67

3.67: Brown solid; Yield 71%; m.p.: 70-72oC. UV-Vis (MeOH) λmax(nm): 294, 226;



(2H, d, Jtrans=15.8 Hz, H-3), 7.47 (4H, ddd, Jp,m,o=0.6, 1.8, 7.8 Hz, H-2’’,6’’), 7.40

(2H, ddd, Jp,m,o=0.5, 1.9, 7.6 Hz, H-4’), 7.35 (2H, d, Jtrans=15.8 Hz, H-2), 7.27

(6H, m, H-3’’, 4’’, 5’’), 6.95 (2H, td, Jm,o=1.8, 7.5 Hz, H-5’), 6.88 (2H, d, Jo=8.3 Hz,

H-3’), 3.91 (4H, t, Jvic=6.2 Hz, OCH2CH2CH2CH2), 1.86 (4H, quintet, Jvic=6.2 Hz,

OCH2CH2CH2CH2), 1.60 (4H, quintet, Jvic=6.2 Hz, OCH2CH2CH2CH2), 1.00

(4H, quintet, Jvic=6.0 Hz, OCH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3):

δ 192.89 (C=O), 157.82 (C-2’), 142.42 (C-3), 135.20 (C-4’’), 133.04 (C-1’), 130.16

(C-1’’), 129.36 (C-6’), 128.85 (C-2’’, 6’’), 128.31 (C-4’), 127.28 (C-5’), 120.68

(C-3’’, 5’’), 112.38 (C-2), 112.30 (C-3’), 68.54 (OCH2CH2CH2CH2), 30.97

(OCH2CH2CH2CH2), 29.17 (CH2CH2CH2CH2), 26.16 (CH2CH2CH2CH2); MS(ESI):

m/z 559 (M+1, 8%), 475 (5%), 453 (3%), 242 (100%), 184 (24%), 142 (38%). Anal.

Calc. for C38O4H38: Calc. C, 81.72 %; H, 6.81 %; Found: C, 81.68 %; H, 6.85 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(decane-1,10-diylbis(oxy))bis(2,1-


The bischalcone 3.68 was prepared by reacting chalcone 3.63 (2.0 g, 0.00840 mol)

with 1,10-dibromodecane (1.260 g, 0.00420168 mol) under the similar conditions as

described earlier for 3.64.

1'

3'

4'

5'

6'


O O

12

3

1''

2''3''

4''

5''6''

3.68



(C-O); 1H-NMR (400 MHz, CDCl3): δ 7.55 (2H, d, Jtrans=15.8 Hz, H-3), 7.51 (2H, dd,

170

Jm,o=1.8, 7.8 Hz, H-6’), 7.48 (4H, td, Jm,o=1.8, 7.8 Hz, H-2’’, 6’’), 7.40 (2H, ddd,

Jp,m,o=1.0, 1.9, 7.6 Hz, H-4’), 7.36 (2H, d, Jtrans=15.8 Hz, H-2), 7.28 (6H, m,

H-3’’, 4’’, 5’’), 6.95 (2H, t, Jo=7.5 Hz, H-5’), 6.90 (2H, d, Jo=8.3 Hz, H-3’), 3.96

(4H, t, Jvic=6.1 Hz, OCH2CH2CH2CH2CH2), 1.65 (4H, quintet, Jvic=6.1 Hz,

OCH2CH2CH2CH2CH2), 1.30 (4H, quintet, Jvic=6.1 Hz, OCH2CH2CH2CH2CH2), 1.18

(4H, m, OCH2CH2CH2CH2CH2), 1.07 (4H, m, OCH2CH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 190.96 (C=O), 158.90 (C-2’), 142.70 (C-3), 135.80 (C-4’’),

132.83 (C-1’), 130.50 (C-1’’), 129.57 (C-6’), 128.53 (C-2’’, 6’’), 128.35 (C-4’),

127.26 (C-5’), 120.64 (C-3’’, 5’’), 112.61 (C-2), 112.14 (C-3’), 68.35

(OCH2CH2CH2CH2CH2), 29.18 (OCH2CH2CH2CH2CH2), 29.00

(CH2CH2CH2CH2CH2), 26.35 (CH2CH2CH2CH2CH2), 26.01 (CH2CH2CH2CH2CH2);

MS(ESI): m/z 609 (M+Na, 78%), 215 (30%), 214 (6%), 158 (33%), 156 (58%), 128

(100%). Anal. Calc. for C40O4H42: Calc. C, 81.91 %; H, 7.16 %; Found: C, 81.86 %;

H, 7.12 %.

Synthesis of (2E, 2’E)-1,1’-(2,2’-(dodecane-1,12-diylbis(oxy))bis(2,1-


The bischalcone 3.69 was synthesized by reacting chalcone 3.63 (2.0 g, 0.00840 mol)

with 1,12-dibromododecane (1.401 g, 0.00420168 mol) under the similar conditions

as described earlier for 3.64.

1'

3'

4'

5'

6'

2'O CH2 (CH2)10 CH2 O

O O

12

3

1''

2''3''

4''

5''6''

3.69



(C-O); 1H-NMR (400 MHz, CDCl3): δ 7.56 (6H, dd, Jm,o=1.8, 7.6 Hz, H-2’’, 4’’, 6’’),

7.39 (2H, d, Jtrans=15.7 Hz, H-3), 7.36 (2H, ddd, Jp,m,o=1.0, 1.9, 7.6 Hz, H-4’), 7.11

(2H, d, Jtrans=15.7 Hz, H-2), 7.00 (4H, d, Jo=8.0 Hz, H-3’, 5’), 6.93 (6H, m, H-6’, 3’’,

5’’), 4.01 (4H, t, Jvic=6.3 Hz, OCH2CH2CH2CH2CH2CH2), 1.72 (4H, quintet,

Jvic=6.3 Hz, OCH2CH2CH2CH2CH2CH2), 1.32 (4H, quintet, Jvic=7.2 Hz,

OCH2CH2CH2CH2CH2CH2), 1.15 (4H, m, OCH2CH2CH2CH2CH2CH2), 1.00 (8H, m,

OCH2CH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 192.98 (C=O), 156.87

171

(C-2’), 142.74 (C-3), 134.09 (C-4’’), 132.80 (C-1’), 130.54 (C-1’’), 129.51 (C-6’),

128.59 (C-2’’, 6’’), 128.19 (C-4’), 127.38 (C-5’), 120.34 (C-3’’, 5’’), 112.62 (C-2),

112.19 (C-3’), 68.62 (OCH2CH2CH2CH2CH2CH2), 29.53

(OCH2CH2CH2CH2CH2CH2), 29.42 (CH2CH2CH2CH2CH2CH2), 29.38

(CH2CH2CH2CH2CH2CH2), 29.28 (CH2CH2CH2CH2CH2CH2), 26.45

(CH2CH2CH2CH2CH2CH2); MS(ESI): m/z 614 (M, 8%), 243 (17%), 242 (100%), 186

(8%), 184 (3%), 142 (2%). Anal. Calc. for C42O4H46: Calc. C, 82.08 %; H, 7.49 %;

Found: C, 82.13 %; H, 7.53 %.

Synthesis of 1,4-bis-[3-(2-oxy-phenyl)-4,5-dihydro-1,5-diphenyl-1H-pyrazole]

butane 3.70

A mixture of bischalcone 3.64 (1.0 g, 0.001886 mol), phenyl hydrazine (0.4080 g,

0.0037735 mol) and glacial AcOH (5 ml) in dry EtOH (30 ml) was refluxed for 8 hrs.

The progress of reaction was monitored by TLC. The resulting reaction mixture was

concentrated under vacuum to obtain a solid substance which was further crystallized

from MeOH to yield pure compound 3.70.

3''

4''

5''

6''

2''1''

12

34

5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)2 CH2 O

NN

HX

HMHA

HM

HA

HX

3.70

3.70: Yellow solid; Yield 63%; m.p.: 130-132oC. UV-Vis (MeOH) λmax(nm): 362,

259; IR (KBr) cm-1: 2928, 2873 (methylene C-H), 1598 (C=N), 1239, 1022 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.92 (2H, dd, Jp,o=1.0, 7.8 Hz, H-6’), 7.28 (10H, m,

H-3’’’, 4’’’, 5’’’, 2’’, 6’’), 7.15 (2H, td, Jm,o=2.0, 7.8 Hz, H-4’), 6.99 (10H, m, H-2’’’,

6’’’, 3’’, 4’’, 5’’), 6.82 (2H, td, Jm,o=1.8, 7.6 Hz, H-5’), 6.63 (2H, d, Jo=8.4 Hz, H-3’),

5.14 (2H, dd, JXM=12.1 Hz, JXA=6.6 Hz, HX), 3.94 (2H, dd, JMX=12.1 Hz,

JMA=17.3 Hz, HM), 3.71 (4H, t, Jvic=6.7 Hz, OCH2CH2), 3.17 (2H, dd, JAX=6.6 Hz,

JAM=17.3 Hz, HA), 1.70 (4H, quintet, Jvic=6.4 Hz, OCH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 156.78 (C-2’), 146.61 (C-3), 146.54 (C-1’’’), 144.95 (C-1’’), 142.79

(C-4’), 140.92 (C-4’’), 129.97 (C-3’’’, 5’’’), 128.95 (C-6’), 128.52 (C-3’’, 5’’),

125.85 (C-2’’, 6’’), 122.12 (C-1’), 120.89 (C-5’), 118.80 (C-4’’’), 113.86 (C-3’),

172

112.27 (C-2’’’, 6’’’), 67.75 (OCH2CH2), 64.35 (C-5), 46.74 (C-4), 26.16 (OCH2CH2);

MS(ESI): m/z 683 (M+1, 18%), 681 (42%), 679 (39%), 592 (26%), 591 (10%), 590

(18%), 589 (80%), 573 (72%), 529 (61%), 511 (18%), 509 (100%), 457 (4%), 434

(15%). Anal. Calc. for C46O2N4H42: Calc. C, 80.93 %; H, 6.15 %; N, 8.21 %; Found:

C, 80.96 %; H, 6.10 %; N, 8.16 %.


pentane 3.71

The compound 3.71 was synthesized from the reaction of bischalcone 3.65 (1.0 g,

0.001838 mol) with phenyl hydrazine (0.3975 g, 0.003676 mol) under the similar

conditions as described above for 3.70.

3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)3 CH2 O

NN

HX

HMHA

HM

HA

HX

3.71

3.71: Brown solid; Yield 67%; m.p.: 136-138oC. UV-Vis (MeOH) λmax(nm): 354,


H-2’’’, 3’’’, 5’’’, 6’’’, 4’), 7.07 (4H, td, Jm,o=2.1, 7.8 Hz, H-2’’, 6’’), 6.91 (2H, dd,

Jp,o=1.1, 7.8 Hz, H-5’), 6.84 (2H, td, Jm,o=1.8, 8.0 Hz, H-4’’), 6.81 (2H, td,

Jp,o=1.1, 8.0 Hz, H-4’’’), 6.72 (4H, td, Jm,o=2.0, 7.8 Hz, H-3’’,5’’), 6.62 (2H, m,

H-3’), 5.09 (2H, dd, JXM=12.1 Hz, JXA=7.0 Hz, HX), 3.82 (4H, m, OCH2CH2CH2),

3.73 (2H, dd, JMX=12.1 Hz, JMA=17.3 Hz, HM), 3.20 (2H, dd, JAX=7.0 Hz,

JAM=17.3 Hz, HA), 1.60 (4H, quintet, Jvic=6.8 Hz, OCH2CH2CH2), 1.41 (2H, quintet,

Jvic=6.8 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 156.06 (C-2’), 146.93

(C-1’’’), 146.54 (C-3), 144.90 (C-1’’), 142.24 (C-4’), 139.91 (C-4’’), 129.25 (C-3’’’,

5’’’), 128.84 (C-6’), 128.73 (C-3’’, 5’’), 125.54 (C-2’’, 6’’), 122.06 (C-1’), 120.59

(C-5’), 118.70 (C-4’’’), 112.97 (C-3’), 112.04 (C-2’’’, 6’’’), 67.72 (O CH2CH2CH2),

64.30 (C-5), 46.70 (C-4), 29.00 (OCH2CH2CH2), 26.51 (OCH2CH2CH2); MS(ESI):

m/z 696 (M, 11%), 695 (19%), 693 (21%), 606 (64%), 605 (28%), 604 (78%), 603

173

(73%), 587 (58%), 547 (25%), 529 (40%), 522 (7%). Anal. Calc. for C47O2N4H44:

Calc. C, 81.03 %; H, 6.32 %; N, 8.04 %; Found: C, 81.08 %; H, 6.35 %; N, 8.09 %.


hexane 3.72

The compound 3.72 was obtained from the reaction of bischalcone 3.66 (1.0 g,

0.001792 mol) with phenyl hydrazine (0.3875 g, 0.003584 mol) under the same

conditions as described earlier for 3.70.

3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)4 CH2 O

NN

HX

HMHA

HM

HA

HX

3.72


254; IR (KBr) cm-1: 2934, 2878 (methylene C-H), 1596 (C=N), 1236, 1025 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.89 (2H, dd, Jm,o=1.7, 7.4 Hz, H-6’), 7.20 (10H, m,

H-3’’’, 5’’’, 4’, 2’’, 6’’), 7.09 (8H, m, H-4’’’, 3’’, 4’’, 5’’), 6.90 (2H, td,

Jm,o=1.9, 7.8 Hz, H-5’), 6.77 (2H, d, Jo=8.0 Hz, H-3’), 6.67 (4H, td, Jp,o=0.6, 7.8 Hz,

H-2’’’, 6’’’), 5.09 (2H, dd, JXM=12.1 Hz, JXA=7.0 Hz, HX), 3.72 (2H, dd,

JMA=17.3 Hz, JMX=12.1 Hz, HM), 3.68 (4H, m, OCH2CH2CH2), 3.23 (2H, dd,

JAX=7.0 Hz, JAM=17.3 Hz, HA), 1.60 (4H, t, Jvic=6.4 Hz, OCH2CH2CH2), 1.32


(C-2’), 146.75 (C-3), 146.72 (C-1’’’), 145.07 (C-1’’), 142.96 (C-4’), 140.96 (C-4’’),

129.70 (C-3’’’, 5’’’), 128.90 (C-6’), 128.22 (C-3’’, 5’’), 125.90 (C-2’’, 6’’), 122.00

(C-1’), 120.86 (C-5’), 118.39 (C-4’’’), 112.62 (C-3’), 112.12 (C-2’’’, 6’’’), 68.27

(OCH2CH2CH2), 64.48 (C-5), 46.89 (C-4), 29.28 (OCH2CH2CH2), 25.79

(OCH2CH2CH2); MS(ESI): m/z 733 (M+Na, 32%), 709 (18%), 707 (27%), 620

(48%), 619 (78%), 618 (54%), 617 (60%), 601 (38%), 536 (10%). Anal. Calc. for

C48O2N4H46: Calc. C, 81.12 %; H, 6.47 %; N, 7.88 %; Found: C, 81.09 %; H, 6.52 %;

N, 7.83 %.

174


octane 3.73

The compound 3.73 was prepared from the reaction of bischalcone 3.67 (1.0 g,



3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)6 CH2 O

NN

HX

HMHA

HM

HA

HX

3.73

3.73: Light yellow solid; Yield 75%; m.p.: 165-167oC. UV-Vis (MeOH) λmax(nm):

352, 253; IR (KBr) cm-1: 2932, 2853 (methylene C-H), 1596 (C=N), 1241, 1028


(14H, m, H-3’’’, 5’’’, 2’’, 3’’, 4’’, 5’’, 6’’), 7. 17 (2H, td, Jm,o=1.9, 7.7 Hz, H-4’), 7.05

(4H, dd, Jp,o=0.6, 7.6 Hz, H-2’’’, 6’’’), 6.98 (2H, td, Jm,o=2.0, 8.0 Hz, H-5’), 6.87

(2H, d, Jo=8.4 Hz, H-4’’’), 6.76 (2H, d, Jo=7.2 Hz, H-3’), 5.18 (2H, dd, JXM=12.2 Hz,

JXA=7.2 Hz, HX), 4.08 (4H, t, Jvic=6.4 Hz, OCH2CH2CH2CH2), 3.93 (2H, dd,

JMX=12.2 Hz, JMA=17.8 Hz, HM), 3.31 (2H, dd, JAX=7.2 Hz, JAM=17.8 Hz, HA), 1.72

(4H, quintet, Jvic=6.6 Hz, OCH2CH2CH2CH2), 1.34 (4H, quintet, Jvic=6.2 Hz,

OCH2CH2CH2CH2), 1.25 (4H, quintet, Jvic=6.2 Hz, OCH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 156.53 (C-2’), 147.98 (C-3), 145.14 (C-1’’’), 144.00 (C-1’’),

142.21 (C-4’), 140.30 (C-4’’), 129.94 (C-3’’’, 5’’’), 128.89 (C-6’), 128.08 (C-3’’,

5’’), 124.78 (C-2’’, 6’’), 121.90 (C-1’), 120.00 (C-5’), 118.77 (C-4’’’), 112.98 (C-3’),

112.16 (C-2’’’, 6’’’), 68.52 (OCH2CH2CH2CH2), 64.55 (C-5), 46.91 (C-4), 29.52

(OCH2CH2CH2CH2), 26.43 (OCH2CH2CH2CH2), 18.45 (OCH2CH2CH2CH2);

MS(ESI): m/z 738 (M, 25%), 737 (5%), 735 (28%), 648 (19%), 647 (61%), 646

(100%), 645 (21%), 629 (10%), 564 (87%), 561 (40%), 543 (30%). Anal. Calc. for


N, 7.53 %.

175


decane 3.74




3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)8 CH2 O

NN

HX

HMHA

HM

HA

HX

3.74


256; IR (KBr) cm-1: 2929, 2855 (methylene C-H), 1594 (C=N), 1236, 1020 (C-O); 1H-NMR (400 MHz, CDCl3): δ 8.02 (2H, d, Jo=7.8 Hz, H-6’), 7.36 (10H, m, H-3’’’,

5’’’, 4’, 2’’, 6’’), 7.14 (6H, m, H-3’’, 4’’, 5’’), 7.12 (4H, m, H-2’’’, 6’’’), 7.10 (2H, d,

Jo=8.0 Hz, H-4’’’), 7.05 (2H, td, Jm,o=2.0, 7.8 Hz, H-5’), 6.80 (2H, d, Jo=8.0 Hz,

H-3’), 5.25 (2H, dd, JXM=12.1 Hz, JXA=6.9 Hz, HX), 4.13 (2H, dd, JMX=12.1 Hz,

JMA=17.2 Hz, HM), 4.02 (4H, t, Jvic=6.4 Hz, OCH2CH2CH2CH2CH2), 3.35 (2H, dd,

JAX=6.9 Hz, JAM=17.2 Hz, HA), 1.78 (4H, quintet, Jvic=6.3 Hz,


(8H, m, OCH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 157.05 (C-2’),

146.91 (C-3), 146.82 (C-1’’’), 144.34 (C-1’’), 142.91 (C-4’), 139.91 (C-4’’), 128.83

(C-3’’’, 5’’’), 128.75 (C-6’), 128.00 (C-3’’, 5’’), 124.67 (C-2’’, 6’’), 121.76 (C-1’),

120.62 (C-5’), 118.65 (C-4’’’), 113.25 (C-3’), 112.20 (C-2’’’, 6’’’), 68.48

(OCH2CH2CH2CH2CH2), 63.31 (C-5), 45.75 (C-4), 29.62 (OCH2CH2CH2CH2CH2),

29.22 (OCH2CH2CH2CH2CH2), 26.38 (OCH2CH2CH2CH2CH2), 25.20

(OCH2CH2CH2CH2CH2); MS(ESI): m/z 766 (M, 100%), 765 (6%), 763 (17%), 676

(8%), 675 (60%), 674 (2%), 673 (43%), 657 (21%), 590 (9%), 589 (9%), 571 (12%),

467 (51%), 448 (49%). Anal. Calc. for C52O2N4H54: Calc. C, 81.46 %; H, 7.04 %;

N, 7.31 %; Found: C, 81.41 %; H, 7.02 %; N, 7.36 %.

176


dodecane 3.75



conditions as used above for 3.75.

3''

4''

5''

6''

2''1''

12

34 5

5''' 3'''

2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)10 CH2 O

NN

HX

HMHA

HM

HA

HX

3.75

3.75: Orange solid; Yield 65%; m.p.: 125-127oC. UV-Vis (MeOH) λmax(nm): 362,


H-4’), 7.19 (10H, m, H-2’’’, 3’’’, 4’’, 5’’’, 6’’’) , 7.05 (4H, td, Jm,o=2.0, 7.8 Hz, H-2’’,

6’’), 7.00 (2H, td, Jp,o=1.1, 7.0 Hz, H-4’’’), 6.92 (2H, td, Jp,o=1.1, 7.8 Hz, H-5’), 6.80

(4H, td, Jm,o=2.2, 7.8 Hz, H-3’’, 5’’), 6.69 (2H, td, Jp,o=1.0, 7.8 Hz, H-3’), 5.12

(2H, dd, JXM=12.1 Hz, JXA=7.1 Hz, HX), 4.00 (2H, dd, JMX=12.1 Hz, JMA=17.3 Hz,

HM), 3.90 (4H, m, OCH2CH2CH2CH2CH2CH2), 3.30 (2H, dd, JAX=7.1 Hz, JAM=17.3

Hz, HA), 1.71 (4H, m, OCH2CH2CH2CH2CH2CH2), 1.30 (4H, m,

OCH2CH2CH2CH2CH2CH2), 1.21 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 155.48 (C-2’), 147.89 (C-3), 146.79 (C-1’’’), 143.35 (C-1’’),

142.88 (C-4’), 139.92 (C-4’’), 128.87 (C-6’), 128.59 (C-3’’’, 5’’’), 128.26 (C-3’’,

5’’), 124.72 (C-2’’, 6’’), 121.87 (C-1’), 120.65 (C-5’), 118.63 (C-4’’’), 112.30 (C-3’),

112.13 (C-2’’’, 6’’’), 68.40 (OCH2CH2CH2CH2CH2CH2), 64.34 (C-5), 44.35 (C-4),

29.60 (OCH2CH2CH2CH2CH2CH2), 29.18 (OCH2CH2CH2CH2CH2CH2), 26.40

(OCH2CH2CH2CH2CH2CH2), 26.22 (OCH2CH2CH2CH2CH2CH2), 25.10

(OCH2CH2CH2CH2CH2CH2); MS(ESI): m/z 795 (M+1, 10%), 793 (48%), 791 (80%),

704 (3%), 703 (4%), 702 (5%), 701 (31%), 685 (2%), 618 (2%), 617 (3%), 599 (1%),

491 (3%), 476 (23%), 304 (40%), 256 (25%), 237 (20%), 158 (13%). Anal. Calc. for


N, 7.08 %.

177

Synthesis of (E)-1-(2-hydroxyphenyl)-3-p-tolylprop-2-en-1-one 3.76

The compound 3.76 was prepared from o-hydroxyacetophenone (5.0 ml, 0.0070 mol)

and tolualdehyde (4.5 ml, 0.0070 mol) under similar conditions as used for 3.63.

O

OH CH33'

4'

5'

6'

1'

2'

12

3

1''

2''

3''

4''

5''

6''

3.76


235; IR (KBr) cm-1: 3217 (O-H), 1690 (C=O), 1600 (C=C); 1H-NMR (400 MHz,

CDCl3): δ 12.87 (1H, s, OH), 7.93 (1H, ddd, Jp,m,o=1.0, 3.0, 8.0 Hz, H-5’), 7.89

(1H, d, Jtrans=15.4 Hz, H-3), 7.62 (1H, d, Jtrans=15.4 Hz, H-2), 7.57 (2H, d, Jo=8.0 Hz,

H-2’’, 6’’), 7.50 (1H, td, Jm,o=1.6, 8.4 Hz, H-4’), 7.24 (2H, d, Jo=8.0 Hz, H-3’’, 5’’),

7.03 (1H, dd, Jp,o=1.0, 8.4 Hz, H-5’), 6.94 (1H, td, Jp,o=1.1, 8.0 Hz, H-3’), 2.40 (3H, s,

CH3); GC-MS: m/z 238 (60%). Anal. Calc. for C16O2H14: Calc. C, 80.67 %;

H, 5.88 %; Found: C, 80.60 %; H, 5.92 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(butane-1,4-diylbis(oxy))bis(2,1-phenylene))bis(3-

p-tolylprop-2-en-1-one) 3.77


0.00820 mol) with 1,4-dibromobutane (0.90754 g, 0.00420168 mol) under the same


1'

3'

4'

5'

6'

2'

O CH2 (CH2)2 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.77


209; IR (KBr) cm-1: 2936, 2871 (methylene C-H), 1656 (C=O), 1598 (C=C), 1235,

1020 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.62 (2H, dd, Jm,o=2.2, 7.6 Hz, H-6’),

7.54 (2H, d, Jtrans=15.9 Hz, H-3), 7.41 (6H, m, H-2’’, 6’’, 4’), 7.29 (2H, d,

Jtrans=15.9 Hz, H-2), 7.12 (4H, d, Jo=7.0 Hz, H-3’’, 5’’), 7.01 (2H, td, Jp,o=0.6, 7.4 Hz,

H-5’), 6.82 (2H, d, Jo=8.2 Hz, H-3’), 3.89 (4H, t, Jvic=6.2 Hz, OCH2CH2), 2.31 (6H, s,

CH3), 1.88 (4H, quintet, Jvic=6.2 Hz, OCH2CH2); 13C-NMR (100 MHz, CDCl3):

δ 192.96 (C=O), 157.44 (C-2’), 142.66 (C-3), 140.68 (C-4’’), 132.79 (C-1’), 132.33

178

(C-1’’), 130.40 (C-6’), 129.63 (C-2’’, 6’’), 129.43 (C-4’), 128.32 (C-5’), 126.49

(C-3’’, 5’’), 120.72 (C-2), 112.25 (C-3’), 67.78 (OCH2CH2), 26.10 (OCH2CH2), 21.46

(CH3); MS(ESI): m/z 554 (M+Na+1, 10%), 553 (M+Na, 21%), 243 (50%), 242

(100%), 186 (9%), 142 (6%). Anal. Calc. for C36O4H34: Calc. C, 81.50 %; H, 6.41 %;

Found: C, 81.44 %; H, 6.45 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(pentane-1,5-diylbis(oxy))bis(2,1-

phenylene))bis(3-p-tolylprop-2-en-1-one) 3.78

The bischalcone 3.78 was prepared from the reaction of chalcone 3.76 (2.0 g, 0.00820

mol) with 1,5-dibromopentane (0.9661342 g, 0.0042016 mol) under the similar


1'

3'

4'

5'

6'

2'

O CH2 (CH2)3 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.78




(2H, d, Jtrans=15.8 Hz, H-3), 7.42 (6H, m, H-2’’, 4’, 6’’), 7.36 (2H, d, Jtrans=15.8 Hz,

H-2), 7.20 (4H, d, Jo=7.2 Hz, H-3’’, 5’’), 7.01 (2H, td, Jp,o=0.7, 7.4 Hz, H-5’), 6.94

(2H, d, Jo=8.4 Hz, H-3’), 4.03 (4H, t, Jvic=6.4 Hz, OCH2CH2CH2), 2.37 (6H, s, CH3),

1.78 (4H, m, OCH2CH2CH2), 1.51 (2H, m, OCH2CH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 192.92 (C=O), 157.53 (C-2’), 142.64 (C-3), 140.62 (C-4’’), 132.80 (C-1’),

132.36 (C-1’’), 130.45 (C-6’), 129.66 (C-2’’, 6’’), 129.48 (C-4’), 128.27 (C-5’),

126.52 (C-3’’, 5’’), 120.75 (C-2), 112.28 (C-3’), 67.74 (OCH2CH2CH2), 29.06

(OCH2CH2CH2), 25.80 (CH2CH2CH2), 21.42 (CH3); MS(ESI): m/z 545 (M+1, 6%),

257 (64%), 256 (100%), 243 (79%), 228 (80%), 200 (37%), 156 (29%), 126 (26%),

110 (12%). Anal. Calc. for C37O4H36: Calc. C, 81.61 %; H, 6.62 %; Found:

C, 81.68 %; H, 6.59 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(hexane-1,6-diylbis(oxy))bis(2,1-phenylene))bis(3-



0.00820 mol) with 1,6-dibromohexane (1.025 g, 0.00420168 mol) under the similar


179

1'

3'

4'

5'

6'

2'

O CH2 (CH2)4 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.79

3.79: Yellow solid; Yield 70%; m.p.:102-104oC. UV-Vis (MeOH) λmax(nm): 322,



7.60 (2H, d, Jtrans=15.9 Hz, H-3), 7.48 (2H, dd, Jm,o=1.8, 7.8 Hz, H-4’), 7.45 (4H, d,

Jo=7.0 Hz, H-2’’, 6’’), 7.37 (2H, d, Jtrans=15.9 Hz, H-2), 7.16 (4H, d, Jo=7.0 Hz,

H-3’’, 5’’), 7.04 (2H, td, Jp,o=0.5, 7.3 Hz, H-5’), 6.92 (2H, d, Jo=8.2 Hz, H-3’), 3.92

(4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 2.31 (6H, s, CH3), 1.62 (4H, quintet, Jvic=6.2 Hz,

OCH2CH2CH2), 1.38 (4H, quintet, Jvic=7.2 Hz, OCH2CH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 192.95 (C=O), 157.66 (C-2’), 142.62 (C-3), 140.64 (C-4’’), 132.83 (C-1’),

132.41 (C-1’’), 130.48 (C-6’), 129.64 (C-2’’, 6’’), 129.50 (C-4’), 128.30 (C-5’),

126.38 (C-3’’, 5’’), 120.67 (C-2), 112.34 (C-3’), 68.32 (OCH2CH2CH2), 29.09

(OCH2CH2CH2), 25.92 (OCH2CH2CH2), 21.45 (CH3); MS(ESI): m/z 582 (M+Na+1,

14%), 581 (M+Na, 24%), 559 (M+1, 3%), 553 (8%), 376 (6%), 365 (9%), 361 (15%),

360 (100%), 339 (4%), 338 (12%), 243 (13%), 242 (90%), 202 (11%). Anal. Calc.

for C38O4H38: Calc. C, 81.72 %; H, 6.81 %; Found: C, 81.77 %; H, 6.84 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(octane-1,8-diylbis(oxy))bis(2,1-phenylene))bis(3-


The bischalcone 3.80 was synthesized from the reaction of chalcone 3.76 (2.0 g,

0.00840 mol) with 1,8 dibromooctane (1.142 g, 0.00420168) under the same


1'

3'

4'

5'

6'

2'

O CH2 (CH2)6 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.80





180


H-5’), 6.95 (2H, d, Jo=8.3 Hz, H-3’), 3.98 (4H, t, Jvic=6.3 Hz, OCH2CH2CH2CH2),

2.32 (6H, s, CH3), 1.67 (4H, quintet, Jvic=7.3 Hz, OCH2CH2CH2CH2), 1.31 (4H, m,

OCH2CH2CH2CH2), 1.09 (4H, m, OCH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3):

δ 192.99 (C=O), 157.74 (C-2’), 142.66 (C-3), 140.58 (C-4’’), 132.84 (C-1’), 132.46

(C-1’’), 130.50 (C-6’), 129.60 (C-2’’, 6’’), 129.56 (C-4’), 128.34 (C-5’), 126.38

(C-3’’, 5’’), 120.66 (C-2), 112.41 (C-3’), 68.58 (OCH2CH2CH2CH2), 29.29

(OCH2CH2CH2CH2), 29.18 (CH2CH2CH2CH2), 26.15 (CH2CH2CH2CH2), 21.48

(CH3); MS(ESI): m/z 611 (M+Na+1, 3%), 610 (M+Na, 32%), 588 (M+2, 6%), 587

(M+1, 10%), 361 (15%), 360 (100%), 339 (4%), 338 (22%), 332 (4%), 202 (12%).

Anal. Calc. for C40O4H42: Calc. C, 81.91 %; H, 7.16 %; Found: C, 81.86 %;

H, 7.19 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(decane-1,10-diylbis(oxy))bis(2,1-



0.00840 mol) with 1,10-dibromodecane (1.260 g, 0.00420168 mol) under the same

reaction conditions as used earlier for 3.64.

1'

3'

4'

5'

6'

2'

O CH2 (CH2)8 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.81






H-5’), 6.96 (2H, d, Jo=8.2 Hz, H-3’), 4.02 (4H, t, Jvic=6.3 Hz,

OCH2CH2CH2CH2CH2), 2.33 (6H, s, CH3), 1.74 (4H, quintet, Jvic=6.3 Hz,


(4H, m, OCH2CH2CH2CH2CH2), 1.05 (4H, m, OCH2CH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 192.96 (C=O), 157.78 (C-2’), 142.64 (C-3), 140.55 (C-4’’),

132.89 (C-1’), 132.42 (C-1’’), 130.54 (C-6’), 129.61 (C-2’’, 6’’), 128.31 (C-4’),

128.25 (C-5’), 126.56 (C-3’’, 5’’), 120.63 (C-2), 112.42 (C-3’), 68.50

181


(CH2CH2CH2CH2CH2), 26.38 (CH2CH2CH2CH2CH2), 26.12 (CH2CH2CH2CH2CH2),

21.40 (CH3); MS(ESI): m/z 638 (M+Na+1, 20%), 637 (M+Na, 60%), 615 (M+1, 6%),

361 (13%), 360 (100%), 339 (4%), 338 (20%), 332 (3%), 243 (11%), 242 (82%), 202

(4%). Anal. Calc. for C42O4H46: Calc. C, 82.08 %; H, 7.49 %; Found: C, 82.14 %;

H, 7.53 %.

Synthesis of (2E,2’E)-1,1’-(2,2’-(dodecane-1,12-diylbis(oxy))bis(2,1-


The bischalcone 3.82 was prepared from the reaction of 3.76 (2.0 g, 0.00840 mol)

with 1,12-dibromododecane (1.401 g, 0.00420168 mol) under the same conditions as


1'

3'

4'

5'

6'

2'

O CH2 (CH2)10 CH2 O

O O

CH3CH312

3

1''

2'' 3''4''

5''6''

3.82



(C-O); 1H-NMR (400 MHz, CDCl3): δ 7.63 (4H, dd, Jm,o=1.8, 7.6 Hz, H-4’, 6’), 7.43

(2H, d, Jtrans=15.8 Hz, H-3), 7.17 (2H, d, Jtrans=15.8 Hz, H-2), 7.02 (4H, d, Jo=8.0 Hz,

H-3’’, 5’’), 6.97 (8H, m, H-2’’, 6’’, 3’, 5’), 4.03 (4H, t, Jvic=6.3 Hz,

OCH2CH2CH2CH2CH2CH2), 2.34 (6H, s, CH3), 1.76 (4H, quintet, Jvic=6.3 Hz,

OCH2CH2CH2CH2CH2CH2), 1.39 (4H, quintet, Jvic=7.2 Hz,



(C-2’), 142.67 (C-3), 140.51 (C-4’’), 132.86 (C-1’), 132.51 (C-1’’), 130.53 (C-6’),

129.59 (C-2’’, 6’’), 128.35 (C-4’), 126.53 (C-3’’, 5’’), 126.39 (C-5’), 120.64 (C-2),

112.44 (C-3’), 68.67 (OCH2CH2CH2CH2CH2CH2), 29.56

(OCH2CH2CH2CH2CH2CH2), 29.48 (CH2CH2CH2CH2CH2CH2), 29.43

(CH2CH2CH2CH2CH2CH2), 29.38 (CH2CH2CH2CH2CH2CH2), 26.28

(CH2CH2CH2CH2CH2CH2), 21.49 (CH3); MS(ESI): m/z 665 (M+Na, 17%), 361

(7%), 360 (31%), 243 (83%), 242 (100%), 241 (12%), 193 (8%), 186 (18%), 184

(6%), 152 (17%), 142 (13%), 106 (16%), 104 (44%). Anal. Calc. for C44O4H50: Calc.

C, 82.24 %; H, 7.78 %; Found: C, 82.28 %; H, 7.82 %.

182

Synthesis of 1,4-bis-[3-(2-oxy-phenyl)-4,5-dihydro-1-phenyl-5-p-tolyl-1H-

pyrazole] butane 3.83


0.001886 mol) with phenyl lhydrazine (0.4080 g, 0.0037735 mol) under the similar


3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)2 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.83



H-3’’’, 5’’’, 4’), 7.15 (4H, td, Jm,o=2.1, 7.6 Hz, H-2’’, 6’’), 7.05 (4H, dd, Jp,o=1.1, 9.0

Hz, H-2’’’, 6’’’), 6.96 (2H, td, Jp,o=1.1, 7.8 Hz, H-5’), 6.86 (2H, d, Jo=7.8 Hz, H-3’),

6.80 (4H, td, Jm,o=2.5, 7.8 Hz, H-3’’, 5’’), 6.72 (2H, dt, Jm,o=2.2, 8.0 Hz, H-4’’’), 5.10

(2H, dd, JXM=12.1 Hz, JXA=7.0 Hz, HX), 3.94 (4H, t, Jvic=5.8 Hz, OCH2CH2), 3.89

(2H, dd, JMX=12.1 Hz, JMA=17.2 Hz, HM), 3.24 (2H, dd, JAX=7.0 Hz, JAM=17.2 Hz,

HA), 2.23 (6H, s, CH3), 1.82 (4H, quintet, Jvic=6.8 Hz, OCH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 156.86 (C-2’), 146.76 (C-3), 145.14 (C-1’’’), 145.12 (C-1’’),

139.99 (C-4’’), 137.05 (C-4’), 129.74 (C-3’’’, 5’’’), 129.69 (C-6’), 128.99 (C-3’’,

5’’), 125.94 (C-2’’, 6’’), 122.18 (C-1’), 120.82 (C-5’), 118.75 (C-4’’’), 113.30 (C-3’),

112.25 (C-2’’’, 6’’’), 67.97 (OCH2CH2), 65.87 (C-5), 45.98 (C-4), 26.28 (OCH2CH2),

21.20 (CH3); MS(ESI): m/z 734 (M+Na+1, 49%), 733 (M+Na, 100%), 616 (10%),

602 (9%), 542 (12%), 541 (21%), 509 (13%), 506 (42%), 483 (11%), 473 (8%), 469



183


pyrazole] pentane 3.84



conditions which are described above for 3.70.

3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)3 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.84



H-2’’’, 3’’’, 5’’’, 6’’’, 4’), 7.11 (4H, td, Jm,o=2.1, 7.8 Hz, H-2’’, 6’’), 6.98 (2H, dd,

Jp,o=1.1, 7.8 Hz, H-5’), 6.86 (2H, td, Jp,o=1.1, 8.0 Hz, H-4’’’), 6.78 (4H, td,

Jm,o=2.0, 7.8 Hz, H-3’’, 5’’), 6.68 (2H, m, H-3’), 5.11 (2H, dd, JXM=12.1 Hz,

JXA=7.0 Hz, HX), 3.86 (4H, m, OCH2CH2CH2), 3.78 (2H, dd, JMX=12.1 Hz,

JMA=17.3 Hz, HM), 3.23 (2H, dd, JAX=7.0 Hz, JAM=17.3 Hz, HA), 2.23 (6H, s, CH3),

1.69 (4H, quintet, Jvic=6.8 Hz, OCH2CH2CH2), 1.44 (2H, quintet, Jvic=6.8 Hz,

OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 156.84 (C-2’), 146.72 (C-3), 145.11

(C-1’’’), 145.08 (C-1’’), 139.98 (C-4’’), 137.00 (C-4’), 129.70 (C-3’’’, 5’’’), 129.66

(C-6’), 128.95 (C-3’’, 5’’), 125.90 (C-2’’, 6’’), 122.15 (C-1’), 120.79 (C-5’), 118.72

(C-4’’’), 113.28 (C-3’), 112.15 (C-2’’’, 6’’’), 67.99 (OCH2CH2CH2), 64.23 (C-5),

46.27 (C-4), 29.10 (OCH2CH2CH2), 28.51 (OCH2CH2CH2), 21.18 (CH3); MS(ESI):

m/z 725 (M+1, 78%), 679 (17%), 678 (32%), 677 (13%), 630 (19%), 629 (10%), 616

(21%), 563 (5%), 562 (22%), 557 (19%), 556 (79%), 555 (41%), 546 (46%), 521

(100%), 520 (21%), 495 (54%), 481 (59%), 467 (23%), 463 (49%), 459 (64%), 453

184

(17%), 427 (40%), 395 (36%), 368 (3%), 367 (61%), 363 (5%), 298 (44%), 188 (3%),

174 (20%). Anal. Calc. for C49O2N4H48: Calc. C, 81.21 %; H, 6.62 %; N, 7.73 %;

Found: C, 81.26 %; H, 6.58 %; N, 7.79 %.


pyrazole] hexane 3.85




3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)4 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.85

3.85: Yellow solid; Yield 75%; m.p. 80-82oC. UV-Vis (MeOH) λmax(nm): 357, 266;

IR (KBr) cm-1: 2939, 2873 (methylene C-H), 1598 (C=N), 1233, 1022 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.99 (2H, dd, Jp,o=1.0, 7.6 Hz, H-6’), 7.29 (6H, m,

H-3’’’, 5’’’, 4’), 7.20 (4H, td, Jm,o=2.1, 7.8 Hz, H-2’’, 6’’), 7.15 (2H, td, Jp,o=1.1, 7.8

Hz, H-5’), 7.12 (4H, dd, Jp,o=1.1, 8.9 Hz, H-2’’’,6’’’), 6.90 (2H, d, Jo=7.8 Hz, H-3’),

6.85 (4H, d, Jo=7.8 Hz, H-3’’, 5’’), 6.75 (2H, td, Jm,o=2.2, 8.0 Hz, H-4’’’), 5.10

(2H, dd, JXM=12.0 Hz, JXA=7.1 Hz, HX), 3.99 (4H, m, OCH2CH2CH2), 3.65 (2H, dd,

JMX=12.0 Hz, JMA=17.2 Hz, HM), 3.33 (2H, dd, JAX=7.1 Hz, JAM=17.2 Hz, HA), 2.20

(6H, s, CH3), 1.65 (4H, m, OCH2CH2CH2), 1.53 (4H, m, OCH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 156.81 (C-2’), 146.73 (C-3), 145.39 (C-1’’’), 145.03 (C-1’’),

139.92 (C-4’’), 137.01 (C-4’), 129.68 (C-3’’’, 5’’’), 129.62 (C-6’), 128.92 (C-3’’,

5’’), 125.88 (C-2’’, 6’’), 122.12 (C-1’), 120.76 (C-5’), 118.70 (C-4’’’), 113.23 (C-3’),

112.12 (C-2’’’, 6’’’), 67.64 (OCH2CH2CH2), 63.48 (C-5), 46.84 (C-4), 29.45

(OCH2CH2CH2), 26.48 (OCH2CH2CH2), 21.14 (CH3); MS(ESI): m/z 761 (M+Na,

4%), 382 (5%), 381 (29%), 353 (42%), 258 (12%), 243 (20%), 242 (100%), 237


C, 81.25 %; H, 6.81 %; N, 7.54 %.

185


pyrazole] octane 3.86




3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)6 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.86



H-4’), 7.16 (10H, m, H-2’’’, 3’’’, 4’’’, 5’’’, 6’’’ ), 7.06 (4H, td, Jm,o=2.0, 8.4 Hz,

H-2’’, 6’’), 6.99 (4H, td, Jm,o=2.0, 8.4 Hz, H-3’’, 5’’), 6.86 (2H, td, Jm,o=2.0, 8.0 Hz,

H-5’), 6.73 (2H, td, Jp,o=1.0, 7.8 Hz, H-3’), 5.16 (2H, dd, JXM=12.0 Hz, JXA=7.1 Hz,

HX), 3.84 (4H, m, OCH2CH2CH2CH2), 3.73 (2H, dd, JMX=12.0 Hz, JMA=17.2 Hz,

HM), 3.04 (2H, dd, JAX=7.1 Hz, JAM=17.2 Hz, HA), 2.27 (6H, s, CH3), 1.72 (4H, m,

OCH2CH2CH2CH2), 1.38 (4H, m, OCH2CH2CH2CH2), 1.18 (4H, m,

OCH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 155.97 (C-2’), 147.90 (C-3),

145.78 (C-1’’’), 144.15 (C-1’’), 138.97 (C-4’’), 135.87 (C-4’), 128.80 (C-3’’, 5’’),

128.61 (C-6’), 128.09 (C-3’’, 5’’), 124.84 (C-2’’, 6’’), 121.11 (C-1’), 119.63 (C-5’),

117.67 (C-4’’’), 112.28 (C-3’), 111.12 (C-2’’’, 6’’’), 67.25 (OCH2CH2CH2CH2),

63.31 (C-5), 45.88 (C-4), 28.33 (OCH2CH2CH2CH2), 25.27 (OCH2CH2CH2CH2),

25.13 (OCH2CH2CH2CH2), 20.22 (CH3); MS(ESI): m/z 790 (M+Na+1, 18%), 789

(M+Na, 39%), 787 (33%), 785 (13%), 779 (14%), 777 (7%), 766 (M, 51%), 765

(100%), 763 (48%), 453 (3%), 441 (12%), 437 (18%), 419 (3%), 345 (14%), 263

(23%), 242 (98%), 237 (80%), 236 (20%), 220 (7%), 202 (8%), 187 (20%), 168

(19%), 105 (38%). Anal. Calc. for C52O2N4H54: Calc. C, 81.46 %; H, 7.04 %;

N, 7.31 %; Found: C, 81.50 %; H, 7.08 %; N, 7.36 %.

186


pyrazole] decane 3.87




3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)8 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.87

3.87: Orange solid; Yield 60%; m.p.: 98-100oC. UV-Vis (MeOH) λmax(nm): 360, 271;

IR (KBr) cm-1: 2921, 2851 (methylene C-H), 1596 (C=N), 1237, 1026 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.97 (2H, dd, Jp,o=1.0, 7.8 Hz, H-6’), 7.37 (2H, m,

H-4’), 7.20 (8H, m, H-2’’’, 3’’’, 5’’’, 6’’’), 7.15 (4H, td, Jm,o=2.0, 7.8 Hz, H-2’, 6’),

7.05 (2H, td, Jp,o=1.1, 7.0 Hz, H-4’’’), 6.98 (2H, td, Jp,o=1.1, 7.8 Hz, H-5’), 6.87

(4H, td, Jm,o=2.2, 7.8 Hz, H-3’’, 5’’), 6.73 (2H, td, Jm,o=1.8, 7.8 Hz, H-3’), 5.17 (2H,

dd, JXM=12.1 Hz, JXA=7.0 Hz, HX), 4.08 (2H, dd, JMX=12.1 Hz, JMA=17.3 Hz, HM),

3.92 (4H, m, OCH2CH2CH2CH2CH2), 3.30 (2H, dd, JAX=7.0 Hz, JAM=17.3 Hz, HA),

2.29 (6H, s, CH3), 1.73 (4H, m, OCH2CH2CH2CH2CH2), 1.36 (4H, m,

OCH2CH2CH2CH2CH2), 1.23 (8H, m, OCH2CH2CH2CH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 155.69 (C-2’), 147.95 (C-3), 146.89 (C-1’’’), 143.38 (C-1’’), 138.89

(C-4’’), 136.90 (C-4’), 128.90 (C-3’’’, 5’’’), 128.88 (C-6’), 128.08 (C-3’’, 5’’),

124.74 (C-2’’, 6’’), 121.90 (C-1’), 120.65 (C-5’), 118.70 (C-4’’’), 113.32 (C-3’),

112.17 (C-2’’’, 6’’’), 68.42 (OCH2CH2CH2CH2CH2), 64.36 (C-5), 46.93 (C-4), 29.64


(OCH2CH2CH2CH2CH2), 26.24 (OCH2CH2CH2CH2CH2), 21.12 (CH3); MS(ESI): m/z

795 (M+1, 12%), 793 (39%), 791 (22%), 742 (6%), 703 (4%), 686 (11%), 685 (28%),

639 (4%), 625 (5%), 599 (11%), 584 (4%), 582 (11%), 507 (10%), 465 (6%), 428

(9%), 382 (12%), 381 (62%), 360 (98%), 353 (100%), 338 (11%), 312 (4%), 298

(19%), 252 (3%), 251 (8%), 250 (48%), 237 (81%), 236 (84%), 222 (93%), 203 (7%),

202 (63%), 186 (6%), 144 (13%), 114 (12%), 102 (22%), 90 (4%). Anal. Calc. for

187


N, 7.02 %.


pyrazole] dodecane 3.88

The compound 3.88 was synthesized from the reaction of bischalcone 3.82

(1.0 g, 0.001502 mol) with phenyl hydrazine (0.3402 g, 0.003012 mol) under the

similar conditions as described earlier for 3.70.

3''

4''

5''

6''

2''1''12

34

5

5''' 3'''2'''6'''

4'''

1'''

1'

2'3'

4'

5'

6' NN

O CH2 (CH2)10 CH2 O

NN

HX

HMHA

HM

HA

HX

CH3 CH3

3.88


256; IR (KBr) cm-1: 2921, 2870 (methylene C-H), 1594, (C=N), 1235, 1023 (C-O); 1H-NMR (400 MHz, CDCl3): δ 7.93 (2H, dd, Jp,o=1.0, 7.8 Hz, H-6’), 7.32 (2H, m,

H-4’), 7.22 (8H, m, H-2’’’, 3’’’, 5’’’, 6’’’), 7. 10 (4H, td, Jm,o=2.0, 7.8 Hz, H-2’’,

6’’), 7.08 (2H, td, Jp,o=1.0, 7.0 Hz, H-4’’’), 6.99 (2H, td, Jp,o=1.0, 7.8 Hz, H-5’), 6.88

(4H, td, Jm,o=2.2, 7.8 Hz, H-3’’, 5’’), 6.74 (2H, td, Jp,o=1.1, 7.8 Hz, H-3’), 5.19

(2H, dd, JXM=12.1 Hz, JXA=7.0 Hz, HX), 4.05 (2H, dd, JMX=12.1 Hz, JMA=17.3 Hz,

HM), 3.94 (4H, m, OCH2CH2CH2CH2CH2CH2), 3.32 (2H, dd, JAX=7.0 Hz,

JAM=17.3 Hz, HA), 2.27 (6H, s, CH3), 1.75 (4H, m, OCH2CH2CH2CH2CH2CH2), 1.33

(4H, m, OCH2CH2CH2CH2CH2CH2), 1.28 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 155.82 (C-2’), 147.97 (C-3), 146.90 (C-1’’’), 143.40

(C-1’’), 138.77 (C-4’’), 136.93 (C-4’), 128.91 (C-3’’’,5’’’), 128.83 (C-6’), 128.02

(C-3’’, 5’’), 124.76 (C-2’’, 6’’), 121.91 (C-1’), 120.68 (C-5’), 118.73 (C-4’’’), 113.34

(C-3’), 112.19 (C-2’’’, 6’’’), 68.34 (OCH2CH2CH2CH2CH2CH2), 64.38 (C-5), 46.81

(C-4), 29.62 (OCH2CH2CH2CH2CH2CH2), 29.22 (OCH2CH2CH2CH2CH2CH2), 26.64


(OCH2CH2CH2CH2CH2CH2), 21.32 (CH3); MS(ESI): m/z 823 (M+1, 65%), 821

(18%), 819 (25%), 731 (80%), 714 (87%), 713 (91%), 667 (26%), 653 (31%), 627

(6%), 612 (95%), 610 (9%), 569 (13%), 535 (37%), 493 (22%), 456 (13%), 410

188

(10%), 409 (18%), 388 (29%), 381 (69%), 366 (40%), 340 (59%), 326 (43%), 264

(62%), 236 (77%), 214 (11%), 172 (7%), 142 (16%), 130 (19%), 118 (83%). Anal.

Calc. for C56O2N4H62: Calc. C, 81.75 %; H, 7.54 %; N, 6.81 %; Found: C, 81.90 %;

H, 7.50 %; N, 6.78 %.

189

References

1. Bart, S.; Halkes, A.; Vrasidas, I. and Rooijer, G. R. Bioorg. Med. Chem. Lett. 2002,

12,1567.

2. Dhar, D. N. The Chemistry of Chalcones and Related Compounds, John Wiley &

Sons, New York, 1981.

3. Grayer, R. J. Methods in Plant Biochemistry, P. M. Dey, J. B. Harborne (Eds.),

Academic Press, London 1989, 1, 283.

4. Bohm, B. A. Methods in Plant Biochemistry, P. M. Dey, J. B. Harborne (Eds.),

Academic Press, London 1989, 1, 237.

5. (a) Krutosikova, A. and Uher, M. Natural and Synthetic Sweet Substances, J.

Hudec (Ed.), Ellis Horwood, New York 1992, 99. (b) Dubois, G. E.; Crosby, G.

A.;Stephenson, R. A. and Wingard, Jr. R. J. Agric. Food Chem. 1977, 25,

763. (c) Dubois, G. E.; Crosby, G. A. and Stephenson, R. A. J. Med. Chem. 1981,

24, 408. (d) Kinghorn, A. D. and Kennelly, E. J. J. Chem. Edu. 1995, 72, 676.

6. Bohm, B. A. The Flavonoids-Advances in Research Since 1986, J. B. Chapman

(Ed.) London, 1994, 387.

7. Harborne, J. B. and Williams, C. A. Phytochemistry 2002, 55, 481.

8. Parmar, V. S.; Bisht, K. S.; Jain, R.; Singh, S.; Sharma, S. K.; Gupta, S.; Malhotra,

S.; Tyagi, O. D.; Vardhan, A.; Pati, H. N.; Berghe, D. V. and Vlietinck, A. J. Ind. J.

Chem. 1996, 35B, 220.

9. (a) Lewis, D. A. Chem. Br. 1992, 141. (b) Esaki, S.; Nishiyama, K.; Sugiyama, N.;

Nakajima, R.; Takao, Y. and Kamiya, S. Biosci. Biotech. Biochem. 1994, 58, 1479.

(c) Bois, F.; Beney, C.; Boumendjel, A.; Mariotte, A. M.; Conseil, G. and Pietro, A.

D. J. Med. Chem. 1998, 41, 4161.

10. Gadow, A.; Joubert, E. and Hansmann, C. F. J. Agri. Food Chem. 1997, 45, 632.

11. (a) Pincemail, J.; Deby, C. and Drieu, K.; Anton, R. Goutier R Proceedings of the

3rd International Symposium on Flavonoids in Biology and Medicine, Singapore,

1989, 161; (b) Jovanovic, S. V.; Steenken, S.; Tosic, M.; Marjanovic, B. and

Simic, M. G. J. Am. Chem. Soc. 1994, 116, 4846; (c) Bors, W.; Heller, W.;

Michel, C.; Stettmaier, K. Handbook of Antioxidants, E. Cadenas, L. Packer

(Eds.), Marcel Dekker, New York 1996, 409; (d) Rice-Evans, C. A.; Miller, N. J.

and Paganga, G. Free Rad. Biol. Med. 1996, 20, 933.

12. Kolos, N. N.; Paponov, B. V.; Orlov, V. D.; Lvovskaya, M. I. L.; Doroshenko, A.

190

O. and Shishkin, O. V. J. Mol. Str. 2006, 785, 114-122.

13. Elguero, J.; In Comprehensive Heterocyclic Chemistry II, Katritzky, A. R.; Rees,

C. W. and Scriven, E. F. V. (Eds.), Pergamon, Oxford, 1996, 3, 1.

14. Yet, L.; In Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden,

C. A.; Scriven, E. F. V. and Taylor, R. J. K. (Eds.), Pergamon, Oxford, 2008, 4, 1.

15. Ulven, T.; Receveur, J. M.; Grimstrup, M.; Rist, O.; Frimurer, T. M.; Gerlach, L.

O.; Mathiesen, J. M.; Kostenis, E.; Uller, L. and Hgberg, T. J. Med. Chem. 2006,

49, 6638.

16. Bonacorso, H. G.; Martins, M. A. P.; Bittencourt, S. R. T.; Lourega, R. V.;

Zanatta, N. and Flores, A. F. C. J. Fluor. Chem. 1999, 99, 177.

17. Martins, M. A. P.; Freitag, R.; Flores, A. F. C. and Zanatta, N. Synthesis 1995,

1491.

18. Martins, M. A. P.; Freitag, R. A.; Rosa, A.; Flores, A. F. C.; Zanatta, N. and

Bonacorso, H. G. J. Het. Chem. 1999, 36, 217.

19. Flores, A. F. C.; Zanatta, N.; Rosa, A.; Brondani, S. and Martins, M. A. P.

Tetrahedron Lett. 2002, 43, 5005.

20. Spingh, S. P. and Vaid, R. K. Ind. J. Chem. 1986, 25B, 288.

21. Knorr, L. B. Dt. Chem. Ges. 1893, 26, 100.

22. Thakare, V. G. and Wadodkar, K. N. Ind. J. Chem. 1986, 25, 610.

23. Ankhiwala, M. D. and Hathi, M. V. J. Ind. Chem. Soc. 1994, 71, 587.

24. Vounauwers, K. and Muller, B. Dt. Chem. Ges. 1908, 41, 4230.

25. Baker, A. and Butt, V. S. J. Chem. Soc. 1949, 2142.

26. Bauer, H. and Piatert, G. German Patent, (DOS) 3039311, 1981; Chem Abstr.

1981, 95, 63146.

27. Evans, N. A. and Waters, P. J. J. Soc. Dyers Colour. 1978, 94, 252.

28. Murayama, T. New Mater. New Proc. Electrochem.Tech. 1981, 1, 92.

29. Poduzhailo, V. F.; Pareyaslova, D. F.; Shripkina, V. I.; Verezubora, S. A. and

Andreeva, L. A. Zh. Prikl. Spektrosk. 1979, 26, 357; Chem. Abstr. 1977, 86,

162579.

30. Tomilovi, Y. V.; Okonnishnikova, G. P.; Shulishov, E. V. and Nefedov O. M.

Russ. Chem. Bt. 1995, 44, 2114.

31. Klimova, E. I.; Marcos, M.; Klimova, T. B.; Cecilio, A. T.; Ruben, A. T. and

Lena, R. R. J. Organomet. Chem. 1999, 585, 106.

32. Bhaskarreddy, D.; Padmaja, A.; Ramanareddy, P. V. and Seenaiah, B. Sulfur Lett.

191

1993, 16, 227.

33. Padmavathi, V.; Sumathi, R. P.; Chandrasekhar, B. N. and Bhaskarreddy, D. J.

Chem. Res. 1999, 610.

34. Bhaskarreddy, D.; Chandrasekhar, B. N.; Padmavathi, V. and Sumathi, R. P.

Synthesis 1998, 491.

35. Roelfvan, S. G.; Arnold, C. and Wellnga, K. J. Agri. Food Chem. 1979, 84, 406.

36. Pelosi, S. S. US Patent 1976, 3946049/3962284.

37. Fahmy, A. M.; Hassan, K. M.; Khalaf, A. A. and Ahmed, R. A. Ind. J. Chem.

1987, 26B, 884.

38. Fuens, R. and Erdelen, C. Ger. Offen. 1995, 4, 336307.

39. Katri, H. Z. and Vunii, S. A. J. Ind. Chem. Soc. 1981, 58, 168.

40. Das, N. B. and Mittra, A. S. Ind. J. Chem. 1978, 16B, 138.

41. Delany, J. US Patent 1991, 4999368.

42. Nugent, R. A.; Murphy, M.; Schlachter, S. T.; Dunn, J. C.; Smith, R. J.; Staite, N.

D.; Galinet, L. A.; Shields, S. K.; Sspar, D. G.; Richard, K. A. and Rohloff, N. A.

J. Med. Chem. 1993, 36, 134.

43. Krishna, R.; Pande, B. R.; Bharthwal, S. P. and Parmar, S. S. Eur. J. Med. Chem.

1980, 15, 567.

44. Husain, M. I. and Shukla, S. Ind. J. Chem.1986, 25B, 983.

45. Ekta, B.; Srivastava V. K. and Kumar, A. Eur. J. Med. Chem. 2001, 36, 81.

46. Satyanarayana, K. and Rao M. N. A. Eur. J. Med. Chem. 1995, 30, 641.

47. Shaw, A. Y.; Liau, H.-H.; Lu, P.-J.; Yang, C.-N.; Lee, C.-H.; Chen, J.-Y.; Xu, Z.

and Flynn, G. Bioorg. Med. Chem. 2010, 18, 3270.

48. Singh, P.; Negi, J. S.; Pant, G. J. N.; Rawat, M. S. M. and Budakoti, A. Molbank

2009, M 614.

49. Jadhav, S. B.; Shastri, R. A.; Gaikwad, K. V. and Gaikwad, S. V. E. J. Chem.

2009, 6(S1), S-183.

50. Li, J.-T.; Zhang, X.-H. and Lin, Z.-P. Beilst. J. Chem. 2007, 3, 13.

51. Jayashankra, B. and Lokanatha R. K. M. E. J. Chem. 2008, 5(2), 309.

52. Sauzem, P. D.; Machado, P.; Rubin, M. A.; Sant’Anna, G. d S.; Faber, H. B.; de

Souza, A. H.; Mello, C. F.; Beck, P.; Burrow, R. A.; Bonacorso, H. G.; Marcos

A.P. and Martins, N. Z. Eur. J. Med. Chem. 2008, 43, 1237.

53. Almeida da Silva, P. E.; Ramos, D. F.; Bonacorso, H. G.; Iglesia, A. I. de la;

Oliveira, M. R.; Coelho, T.; Navarini, J.; Morbidoni, H. R.; Zanatta, N. and

192

Martins, M. A. P. Inter. J. Antimic. Agents 2008, 32, 139.

54. Ali, M. A.; Shaharyar, M. and Siddiquig, A. A. Eur. J. Med. Chem. 2007, 42, 268.

55. Revanasiddappa, B. C.; Rao, R. N.; Subrahmanyam, E. V. S. and Satyanarayana,

D. E. J. Chem. 2010, 7(1), 295.

56. Sahoo, A.; Yabanoglu, S.; Sinha, B. N.; Ucar, G.; Basu, A and Jayaprakash, V.

Bioorg. Med. Chem. Lett. 2010, 20, 132.

57. Jayaprakash, V.; Sinha, B. N.; Ucar, G. and Ercan, A. Bioorg. Med. Chem. Lett.

2008, 18, 6362.

58. Hayat, F.; Salahuddin, A.; Umar, S. and Azam, A. Eur. J. Med. Chem. 2010, 45,

4669.

59. Conti, P.; Pinto, A.; Tamborini, L.; Rizzo, V. and Micheli, C. D. Tetrahedron

2007, 63, 5554.

60. Shevtson, A. V.; Kislukhin, A. A.; Kuznetson, V. V.; Petukhova, V. Y.;

Maslennikov, V. A.; Borissova, A. O.; Lyssenko, K. A. and Makhova, N. N.

Mandel. Commun. 2007, 17, 119.

61. Mishra, S. K.; Sahoo, S.; Panda, P. K.; Mishra, S. R.; Mohanta, R. K.; Ellaiah, P.

and Panda, C. S. Acta Poloniae Pharm. Drug Res. 2007, 64(4), 359.

62. Padmavathi, V.; Radhalakshmi, T.; Mahesh, K. and Mohan, A. V. N. Ind. J.

Chem. 2008, 47B, 1707.

63. Alex, K.; Tillack, A.; Schwarz, N. and Beller, M. Org. Lett. 2008, 10(12), 2377.

64. Insuasty, B.; Martinez, H.; Quiroga, J.; Abonia, R.; Nogueras, M. and Cobo, J.

J. Het. Chem. 2008, 45, 1521.

65. Biagini, P.; Biancalani, C.; Graziano, A.; Cesari, N. Giovannoni, M. P.; Cilibrizzi,

A.; Piaz, V. D.; Vergelli, C.; Crocetti, L.; Delcanale, M.; Armani, E.; Rizzi, A.;

Puccini, P.; Gallo, P. M.; Spinabelli, D. and Caruso, P. Bioorg. Med. Chem.

2010, 18, 3506.

66. Bondock, S.; Fadaly, W. and Metwally, M. A. Eur. J. Med. Chem. 2010, 45, 3692.

67. Bhat, A. R.; Athar, F. and Azam, A. Eur. J. Med. Chem. 2009, 44, 426-431.

68. Barsoum, F. F.; Hosni H. M. and Girgis, A. S. Bioorg. Med. Chem. 2006, 14,

3929.

69. Insuasty, B.; García, A.; Quiroga, J.; Abonia, R.; Ortiz A.; Nogueras, M. and

Cobo, J. Eur. J. Med. Chem. 2011, 46, 2436.

70. (a) Gennari, C. Comprehensive Organic Synthesis, Trost, B. M. and Fleming, I.

193

(Eds.), Pergamon, Oxford, UK, 1991, 2, 629; (b) Mahrwald, R. (Ed.), Modern

Aldol Reactions; Wiley, VCH, Weinheim, Germany, 2004, 1-2; (c) Mukaiyama,

T.Organic Reactions, Dauben, W. G. (Eds.), J. Wiley & Sons: New York, NY,

USA, 1982, 28, 203; (d) Healthcock, C. H. Comprehensive Organic Synthesis,

Trost, B. M. And Fleming, I. (Eds.), Pergamon, Oxford, UK, 1991, 2, 133.

71. Baurer, A. W.; Kirby, M. M.; Sherris, J. C. and Turck, M. Am. J. Clinic. Path.

1966, 45, 493.

72. Pandey, K. S. and Khan, N. Arch. Pharm. Chem. Life Sci. 2008, 341, 418.

194

Chapter-IIIb Synthesis of new 1,3-diphenyl-5-thienyl-


� Synthesis and Antimicrobial Studies of New Bis[4,5-dihydro-1- phenyl-5-

thienyl- 3-(phenyl-4-alkoxy)-1H-pyrazole] Derivatives


Journal of Heterocyclic Chemistry 2012, doi:10.1002/jhet.1805.

195

In the chapter IIIa , the researches were oriented upon the preparation of

1,3,5-triphenyl-bispyrazolines. In this chapter (IIIb) , we plan to prepare thienyl

substituted bispyrazolines. The presence of thiophene may affect the formation and

biological behaviour of the resulting heterocyclic compounds. In the literature, some

examples are reported upon the synthesis of pyrazoline derivatives bearing thiophene

moiety and these substrates are found to exhibit significant biological activity. These

compounds are obtained from the cyclization reaction of thienyl/furyl substituted

chalcones with suitable hydrazine derivatives.

A series of 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives

3.90 were synthesized by Bao-Xiang Zhao and et al1 (Scheme-3.25) and the effects

of these compounds on the growth of A549 cell have also been investigated. The

study on structure activity relationships and prediction of lipophilicities of compounds

showed that heterocyclics with Log P values in the range of 4.12-6.80 had significant

inhibitory effects on the growth of A549 cell and the hydrazones derived from

salicylaldehyde had much more inhibitory effects.

X

NN

O

NHNH2

R2

R1

X

NN

O

NHN

R2

Ar

R1

EtOH

R1= H, Cl, OMe; R2 = H, Cl, t-Bu, X= C, N

Ar = , , ,

3.89 3.90

ArCHO

O

O

OH OMe

O

Scheme-3.25

The tricyclic fused pyrazolines 3.92 have been prepared (Scheme-3.26) from the

reaction of 3-arylidenechromanones/thiochromones 3.91 with

4-carboxyphenyl-hydrazine in hot anhydrous pyridine solution.2

X

O

RNH NH2HOOC

Pyridine

where X= O, S, SO2 ; R= H, Me, MeO, F, Cl, Br

3.91

3.92

X

NNH

COOH

R

Scheme-3.26

196

The reaction of substituted carboxylic acid hydrazides 3.93 with ethane-

tetracarbonitril in dimethyl formamide (Scheme-3.27) led to the formation3 of

diacylhydrazines 3.94 and 5-amino-1-substiuted pyrazole-3,3,4-tricarbonitriles 3.96.

R C

O

NH NH2 R C

O

NH NH C RO

+ NNH

NH2

CN

CN

CN

O

R

N

NH

O

H

NH

CN

CN

CN

R

R = , , , CH3

SCH3

N CH3NH

CH3

DMF

3.93 3.943.95 3.96

Scheme-3.27

New pyrazolines 3.100 have been synthesized4 from the cyclocondensation reaction

chalcones 3.99 with phenyl hydrazine (Scheme-3.28).

C

O

CH3 +X

CHOR

C

O

CH CHX

R

R

NN

X

HH

H

Alc. NaOH

3.973.98

3.99

3.100

X = O NH2NH

Scheme-3.28

Some other examples are also available in the literature upon the synthesis of

thienyl/furyl substituted pyrazolines.5

The above literature survey clearly describes that there is a need to explore the

synthesis and antimicrobial activities of thienyl substituted pyrazoline/bispyrazolines.

On the basis of these aspects, we have oriented our researches upon the synthesis of

new thiophene based bispyrazolines 3.109-3.115.

SN

N

O CH2 (CH2)n CH2 O

NN

S

HM

HA

HX

HM

HA

HX

3.109-3.115

n = 1, 2, 3, 4, 6, 8, 10

197

The bispyrazolines 3.109-3.115 required for the present studies were synthesized from

the cyclization reactions of bischalcones 3.102-3.108 with phenyl hydrazine by

refluxing under EtOH/AcOH medium. The bischalcones were obtained from the

O-alkylation of chalcone 3.101 with suitable alkylating agents (1,3-dibromopropane,

1,4-dibromobutane, 1,5-dibromopentane, 1,6-dibromohexane, 1,8-dibromooctane,

1,10-dibromodecane & 1,12-dibromododecane). The compound 3.101 was prepared

from the Claisen-Schmidt6 reaction of 4-hydroxyacetophenone with

2-thiophenecarboxaldehyde. The structures of prepared compounds were determined

from the rigorous analysis of their IR, 1H-NMR, 13C-NMR & ESI-MS spectral data.

The elemental analysis results were also helpful to confirm the purity of these

products.

Synthesis of Chalcone 3.101

The chalcone 3.101 was obtained from the reaction of 4-hydroxyacetophenone with

2-thiophenecarboxaldehyde under NaOH/EtOH medium (Scheme-3.29). The

decomposition of the reaction mixture into iced HCl provided a crude substance

which was crystallized from MeOH to yield pure compound 3.101

(65%, m.p. 166-168οC).

OH

O

CH3

+

O

S

OH

NaOH/ EtOH/00C

SCHO

4''

1''

2 ''

3''

5 ''1

2

31'

2 '

3 '

4 '

5 '

6 '

3.101

Scheme-3.29

The IR spectrum of 3.101 showed three major absorptions at 3229 (O-H), 1688 (C=O)

& 1600 (C=C) cm-1. In its 1H-NMR spectrum (400 MHz, CDCl3), a D2O

exchangeable singlet was placed at δ 10.25 that can be ascribed to OH proton. The

double bond and theinyl ring hydrogens were very well resonating at δ 7.96 (1H, d,

Jtrans=15.1 Hz, H-3), 7.60 (1H, d, Jtrans=15.1 Hz, H-2), 7.12 (1H, d, J5’’,4’’ =4.8 Hz,

H-5’’), 7.43 (1H, d, J3’’,4’’ =3.7 Hz, H-3’’) and 6.89 (1H, d, J4’’,3’’ =3.7 Hz, H-4’’). The

GC-MS spectrum of 3.101 exhibited the molecular ion at m/z 230 (70%) which also

corroborated its structure.




198

The compound 3.101 was reacted with 1,3-dibromopropane in the presence of

anhydrous K2CO3 and tetrabutyl ammonium iodide (PTC) in dry acetone

(Scheme-3.30). The resulting reaction mixture was poured into iced-HCl to give a

solid substance. The crude product thus obtained was purified by crystallization from

CHCl3:MeOH (1:1) to yield pure bischalcone 3.102 (60%, m.p. 110-112oC).

O

S

OH

3.101

3''4''

5''6'2''

anhd. K2CO3 /BrCH2CH2CH2Br/ dry acetone/Bu4N+I-/∆

1''

4'

5'

3'2'

1'12

3

4''

1''

2 ''

3''

5 ''1

2

31'

2 '

3 '

4 '

5 '

6 '

SO

O CH2 CH2 CH2 O

OS

3.102

Scheme-3.30

The compound 3.102 in its IR spectrum exhibited strong absorption at 1660 cm-1 that

may be assigned to C=O group and other noticeable bands were observed at 1596

(C=C) and 1236, 1034 cm-1 (C-O). Its ESI-MS spectrum exhibited (M+1) ion at m/z

501 (9%) and its mass fragmentation has been shown in Chart-1 which clearly

confirm the proposed structure. UV-Vis spectrum of 3.102 exhibited two maxima at

280 and 234 nm which may be ascribed to n→π* and π→π* transitions respectively.

In the 1H-NMR (400 MHz, CDCl3) spectrum of 3.102, two doublets (Jo=8.5 Hz)

placed at δ 8.00 and 7.03 may be furnished by H-2’, 6’ and H-3’, 5’ respectively. The

signals present at δ 7.84 (2H, d, Jtrans=14.5 Hz), 7.51 (2H, d, J5’’,4’’ =4.9 Hz), 7.43

(4H, m) and 7.13 (2H, d, J4’’,3’’ =3.8 Hz) may be ascribed to H-3, H-5’’, H-2, 3’’ and

H-4’’ respectively. The intervening chain methylene protons were located at δ 4.29

(4H, t, Jvic=5.8 Hz, OCH2) and 2.08 (2H, t, Jvic=5.8 Hz, OCH2CH2).

13C-NMR (100 MHz, DMSO-d6) spectrum of 3.102 provided the signal of C=O, C-4’,

C-3 and C-2 at δ 186.60, 162.48, 139.80 and 120.10 respectively. The remaining

resonances in the aromatic region were found to be placed at δ 135.73 (C-2’’), 131.94

199

(C-1’), 130.48 (C-2’, 6’), 130.25 (C-5’’), 129.32 (C-3’’), 128.20 (C-4’’) and 114.10

(C-3’, 5’). The carbon atoms of the symmetrical internal spacer furnished two signals

at δ 67.28 (OCH2CH2) and 25.20 (OCH2CH2).

S O

O CH2 CH2 CH2 O

OS

O

O CH2 CH2 CH 2 O

O

O

CH2 CH2 CH2 O

O

O

CH2 CH2 CH2 O

O

O

C C CH2 O

O

C C CH2 O

O

C C CH2 OCH 2 O

H

H2C O

H

S O

O CH CH CH2 O

O

C

S O

O CH CH CH2 O

C

C C CH2 O

C

S O

S O

m/z 501 (M+1, 9%)

m/z 500

m/z 436 (19%)

m/z 394 (8%)

m/z 339 (41%)

m/z 335 (14%)

m/z 307 (86%)

m/z 279 (28%)m/z 183 (71%)

m/z 107 (33%)

m/z 411 (22%)

m/z 383 (42%)

m/z 365 (11%)

m/z 135 (74%)

-2S

-C2H2O

-C4H7

-4H

-CO

-CO

+

+

++

+

+

+

+

+

+

-C4H9S

-CO

-H2O

+

+

+

.

.

.

......

....

....

......

....

....

......

......

.

......

.

-C6H5

......

.

Chart-1


The compound 3.102 was refluxed with phenyl hydrazine in EtOH/AcOH solution

(Scheme-3.31) and cooling of the resulting reaction mixture in an ice bath furnished a

200

solid substance. The crude product was crystallized from MeOH to yield pure

compound 3.109 (62%, m.p. 99-101oC).

3''4''

5''6'2''

1''

4'

5'

3'2'

1'12

3

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

S O

O CH2 CH2 CH2 O

OS

SN

N

O CH2 CH2 CH2 O

NN

S

HM

HA

HX

HM

HA

HX

PhNHNH2/dry EtOH/ AcOH/∆

3.102

3.109

Scheme-3.31

IR spectrum of 3.109 showed a significant band at 1593 cm-1 due to the C=N moiety

of pyrazoline ring. Its ESI-MS spectrum was very helpful to interpret the proposed

expression which had (M+Na) ion at m/z 703 (7%) and the other noticeable ions were

placed at m/z 614 (80%), 420 (33%), 377 (53%), 303 (25%), 297 (62%) and 221

(89%). Its mass fragmentation pattern has been depicted in Chart-2.

In the 1H-NMR of 3.109, there was a doublet at δ 7.63 (4H, Jo=8.6 Hz) which may be

assigned to H-2’’’, 6’’’ and next to it was another doublet at δ 7.33

(2H, J3’’,4’’ =3.7 Hz) which could be furnished by H-3’’. Another doublet integrating

for two hydrogens at δ 7.22 (J5’’,4’’ =5.0 Hz) was denoted by H-5’’. The aromatic

protons H-3’’’, 5’’’ appeared as a doublet at δ 6.99 (4H, Jo=8.6 Hz) and H-3’, 4’, 5’ &

H-2’, 6’ were centred at δ 7.12 & 6.70 as a six hydrogens multiplet and four

hydrogens triplet (Jo=7.2 Hz) respectively. A doublet of doublet present at δ 6.89

(2H, J4’’,3’’ =3.7 Hz, J4’’,5’’ =5.0 Hz) may be assigned to H-4’’ proton. Three signals

corresponding to H-X, H-M and H-A were resonating at δ 5.60 (2H, dd, JXA=6.2 Hz,

JXM=11.8 Hz), 3.82 (2H, dd, JMX=11.8 Hz, JMA=17.2 Hz) and 3.19 (2H, dd,

JAX=6.2 Hz, JAM=17.2 Hz) respectively. A triplet present at δ 4.02 (4H, Jvic=5.8 Hz)

and a quintet at δ 2.50 (2H, Jvic=5.8 Hz) were easily provided by the protons of

OCH2CH2 and OCH2CH2 group respectively. UV-Vis spectrum of 3.109 had two

201

maxima at 360 and 255 nm which may be provided by n→π* and π→π* transitions

respectively.

SN

N

O CH2 CH2 CH2 O

NN

S

H

H

H

H

H

H

NN

O CH2 CH2 CH2 O

NN

H

H

H

O CH2 CH2 CH2 O

NN

CH2 CH2 CH2 O

H2C CH2 CH2 O

O CH2 CH2 CH2 O

NN

S

H

H

H

NN

S

H

H

H

NN

H

H

H

NH

N

HH

H

m/z 680

m/z 614 (80%)

m/z 420 (33%)

m/z 297 (62%)

m/z 220 (17%)

m/z 377 (53%)

m/z 303 (25%)

m/z 221 (89%)

m/z 145 (10%)

-H2S2

-C6H7N2O

-C6H5

-C3H6O2

+

+

+

++

+

+

.....

.....

..... .....

.....

.

.

.

.

.

.

+

.........

.... +.

-C4SH2

-C6H4

a

-C19N2SH15

-C13N2H10

m/z 703 (M+Na, 7%)

Chart-2 13C-NMR spectrum of 3.109 provided enough evidence in favour of its carbon

framework. The signals located at δ 160.15, 154.26 and 145.15 were represented by

C-4’’’, C-3 and C-1’ respectively due to their direct linkage to the electronegative

atom (N & O). The remaining aromatic carbon atoms were found to be resonating at

δ 147.34 (C-2’’), 144.87 (C-1’’’), 128.03 (C-5’’), 127.55 (C-3’’), 126.26 (C-4’’),

126.30 (C-2’’’, 6’’’), 124.68 (C-3’, 5’), 118.60 (C-4’), 114.90 (C-3’’’,5’’’) and 113.77

(C-2’, 6’). The pyrazoline ring carbons C-5 and C-4 were suitably placed at δ 59.41 &

202

43.39 respectively. The intervening chain OCH2CH2 and OCH2CH2 group were

represented by two signals at δ 67.10 and 24.47 respectively.


The compound 3.110 was again obtained in the two steps:


The chalcone 3.101 was reacted with 1,4-dibromobutane (Scheme-3.32) under the


(70%, m.p. 172-174οC).

O

S

OH

3.101

3''4''

5'' 6'2''

Anhd. K2CO3 /BrCH2(CH2)2CH2Br/ dry acetone/Bu4N+I-/∆

1''

4'

5'

3'2'

1'12

3

4''

1''

2 ''

3''

5 ''1

2

31'

2 '

3 '

4 '

5 '

6 '

S O

O CH2 (CH2)2 CH2 O

OS

3.103

Scheme-3.32

IR spectrum of 3.103 showed strong absorptions at 1652 and 1595 cm-1 which are the

characteristic band of C=O and C=C group respectively. In its 1H-NMR (400 MHz,

CDCl3) spectrum, two doublets corresponding to four protons each H-2’, 6’ and

H-3’, 5’ were placed at δ 8.02 (Jo=8.8 Hz) and 7.01 (Jo=8.8 Hz) respectively. The

thienyl ring protons H-5’’, 3’’ & H-4’’ furnished three signals at δ 7.61 (2H, d,

J5’’,4’’ =5.0 Hz), 7.52 (2H, d, J3’’,4’’ =3.7 Hz) and 7.11 (2H, dd, J4’’,3’’ =3.7 Hz,

J5’’,4’’ =5.0 Hz) respectively. The hydrogens (H-3 & H-2) of the double bond were

centred at δ 7.83 (2H, d) & 7.45 (2H, d) and the coupling value of J2,3=15.2 Hz

describes their trans relationship. A triplet at δ 4.14 (4H, Jvic=5.8 Hz) and a quintet at

δ 1.96 (4H, Jvic=5.8 Hz) were assignable to the internal chain OCH2CH2 and

OCH2CH2 group respectively. UV-Vis spectrum of 3.103 had two maxima at 276 and

227 nm which may be ascribed to n→π* and π→π* transitions respectively.

ESI-MS spectrum of 3.103 was also helpful to corroborate the given structure which

exhibited the (M+1) ion at m/z 515 (6%) along with other ions at m/z 448 (100%),

447 (3%), 425 (6%), 406 (76%), 405 (44%), 387 (30%) and 353 (34%)

203

(vide experimental). Its mass fragmentation pattern was found to be similar as shown

in Chart-1 (vide experimental). 13C-NMR spectrum of 3.103 contained the signals of enone moiety at δ 186.65 (C-1),

139.84 (C-3) and 120.13 (C-2). The carbon atom (C-4’) bonded to oxygen atom

resulted a signal at δ 162.45. The intervening chain OCH2CH2 and OCH2CH2 group

could contribute two resonances at δ 67.37 and 25.26 respectively. The aromatic ring

carbon atoms (C-1’, 2’, 3’, 5’, 6’ & C-2’’, 3’’, 4’’, 5’’) were found to be resonating at

the expected position (vide experimental).


The compound 3.110 (68%, m.p. 145-147oC) was prepared from the reaction of 3.103

with phenyl hydrazine (Scheme-3.33) under the similar conditions as used earlier for

3.109.

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

S O

O CH2 (CH2)2 CH2 O

OS

SN

N

O CH2 (CH2)2 CH2 O

NN

S

HMHA

HX

HM

HA

HX

PhNHNH2/ dry EtOH/ AcOH/∆

3.103

3.110

Scheme-3.33

In addition to the IR spectrum of 3.110 confirming the presence C=N functionality at

1597 cm-1, its 1H-NMR spectrum (400 MHz, DMSO-d6) also fully lent support to the

proposed structure. Here, three hydrogens H-X, H-M & H-A belonging to the

pyrazoline ring furnished well defined doublet of doublet each at δ 5.67

(2H, JXA=6.2 Hz, JXM=11.8 Hz), 3.86 (2H, JMX=11.8 Hz, JMA=17.2 Hz) and 3.21

(2H, JAX=6.2 Hz, JAM=17.2 Hz) respectively. The thienyl ring protons were found to

be resonating at δ 7.30 (2H, d, J3’’,4’’ =3.7 Hz, H-3’’), 7.17 (2H, d, J5’’,4’’ =5.0 Hz,

H-5’’) and 6.92 (2H, dd, J4’’,3’’ =3.7 Hz, J4’’,5’’ =5.0 Hz, H-4’’). Two more doublets

integrating for four hydrogens each at δ 7.67 (Jo=8.6 Hz) and 6.95 (Jo=8.6 Hz) were

204

easily assignable to H-2’’’, 6’’’ & H-3’’’, 5’’’ respectively. A multiplet integrating for

six protons (H-3’, 4’, 5’) appeared at δ 7.09 while four protons (H-2’, 6’) furnished a

triplet at δ 6.73 (Jo=7.2 Hz). The two broad singlets present at δ 4.09 (4H) & 2.52

(4H) may be allotted to the protons of OCH2CH2 & OCH2CH2 group respectively.

In the 13C-NMR spectrum (100MHz, CDCl3) of 3.110, the carbon atom (C-4’’’, C-3

& C-1’) directly bonded to the heteroatom (O & N) were resonating at δ 160.12,

155.56 and 145.85 respectively. The remaining aromatic carbons were found to be

placed at the expected δ values (vide experimental). The signals present at δ 59.47,

43.41 could be furnished by pyrazoline ring carbons C-5 and C-4 respectively. In the

upfield region, two signals were also located at δ 67.13 (OCH2CH2) and 25.37

(OCH2CH2). The UV-Vis spectrum of 3.110 had two maxima at 368 and 263 nm due

to to n→π* and π→π* transitions respectively.

Encouraged by the above described facile cyclization reactions, it was considered to

be of major interest to extend this study on the bischalcones 3.104-3.108. The major

interest in these reactions was to investigate the effect of lengthy internal chains upon

the formation and antimicrobial behaviour of the bispyrazoline 3.111-3.115.



chalcone 3.101 with suitable 1,ω-dibromoalkane (1,5-dibromopentane,

1,6-dibromohexane, 1,8-dibromooctane, 1,10-dibromodecane &

1,12-dibromododecane respectively) under the similar conditions as described earlier

for 3.102-3.103. The significant spectral parameters of these compounds have been

presented in Table-1 (Plate-33-37 & vide experimental).

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)n CH2 O

OS

3.104 (n=3), 3.105 (n=4), 3.106 (n=6), 3.107 (n=8), 3.108 (n=10)

205


*Jtrans= 15.3-14.9 Hz

Synthesis of bispyrazoline 3.111-3.115

The compounds 3.111-3.115 were prepared from the cyclization reaction of the


described earlier for 3.109. The physical and characteristic spectral data of

3.111-3.115 have been provided in Table-2 (Plate-38-41 & vide experimental).

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)n CH2 O

NN

S

HM

HA

HX

HM

HA

HX

3.111 (n=3), 3.112 (n=4), 3.113 (n=6), 3.114 (n=8), 3.115 (n=10)

Compd. m.p. (°C)

Yield (%)

IR (υmaxcm-1)

1H-NMR (δ) 13C-NMR (δ) ESI-MS (m/z)

C=O C=C H-3* H-2* C=O C-3 C-2

3.104 155-157

68

1656

1598

7.84 7.44

186.68 139.80 120.15 551 (M+Na)+

3.105 197-199

72

1657

1602

7.93

7.32

186.69 140.68 120.27 565 (M+Na)+

3.106 140-142 78 1658 1597 7.91 7.45 186.60

139.82 120.05 593 (M+Na)+

3.107 118-120 75 1652 1596 7.94

7.43

186.66 139.80 120.23 599 (M+1)+

3.108 130-132 80 1654 1595 7.93 7.36 186.86 139.78 120.33 649 (M+Na)+

206


*JAX=6.9-6.2 Hz, JMX= 12.2-11.8 Hz, JMA=17.4-16.5 Hz.

Antimicrobial evaluations of bischalcones 3.102-3.108 & bispyrazolines

3.109-3.115

The in vitro antimicrobial activities of compounds 3.102-3.108 & 3.109-3.115 were

analysed against seven bacterial strains namely Klubsellia pneumoniae (MTCC 3384),

Pseudomonas aeruginosa (MTCC 424), Escherichia coli (MTCC 443),

Staphylococcus aureus (MTCC 96), Bacillius subtilis (MTCC 441), Pseudomonas

fluorescens (MTCC 103), Streptoccus pyrogens (MTCC 442) and five fungi strains

namely Aspergillius janus (MTCC 2751), Aspergillius niger (MTCC 281), Fusarium

oxysporum (MTCC 2480), Aspergillus sclerotiorum (MTCC 1008) & Pencillium

glabrum (MTCC 4951). The MIC of these compounds were evaluated by using serial

tube dilution method7 and according to the similar procedure which is described on

page no. 43,44 (Chapter-IIa) . Amoxicillin and Fluconazole were used as reference

drugs for antibacterial and antifungal activities respectively. The observed minimum

inhibitory concentrations (MIC-µg/ml) of the studied compounds 3.102-3.108 &

3.109-3.115 have been presented in Table-3 (Figure-1) and Table-4 (Figure-2)

respectively.

Compd. m.p

(°C)

Yield

(%)

IR

(υmax

cm-1)

1H-NMR (δ)

13C-NMR (δ)

ESI-MS (m/z)


3.111 125- 127

65 1592 5.62

3.81

3.24

155.50 59.49 43.47 709 (M+1)+

3.112 166-168

61 1599 5.59 3.85

3.23

155.58 59.59 43.50 723 (M+1)+

3.113 152-154

70 1595 5.58 3.83 3.22 155.78 59.74 43.62

750 (M)+

3.114 126-128

60 1596 5.56 3.82 3.20 156.23 59.73 43.54

779 (M+1)+

3.115 110-112

63 1596 5.60 3.84 3.21 155.42 59.62 43.25 829 (M+Na)+

207

Table-3. In vitro MIC (µg/ml) of bischalcones 3.102-3.108

Gram negative bacteria Gram positive bacteria Fungi

Compound E.

coli

K..

pneumoniae

P.

aeruginosa

P.

fluorescens

S.

aureus

B.

subtilis

S.

pyrogens

A.

janus

P.

glabrum

A.

niger

F.

oxysporum

A.

sclerotiorum

3.102 50 25 50 50 50 50 25 50 50 25 25 50

3.103 50 25 25 50 50 25 25 50 25 25 50 50

3.104 25 12.5 12.5 25 50 25 25 25 25 12.5 12.5 12.5

3.105 50 25 25 12.5 50 12.5 12.5 25 25 12.5 12.5 12.5

3.106 25 25 25 12.5 25 25 12.5 12.5 25 12.5 12.5 25

3.107 25 25 12.5 12.5 25 25 12.5 25 12.5 25 12.5 25

3.108 25 50 12.5 12.5 25 12.5 12.5 100 12.5 12.5 25 25

Amoxicillin 6.25 6.25 6.25 3.12 3.12 6.25 6.25 - - - - -

Fluconazole

- - - - - - - 3.12 3.12 6.25 3.12 3.12

208

Table-4. In vitro MIC (µg/ml) of bispyrazolines 3.109-3.115

Gram negative bacteria Gram positive bacteria Fungi

Compd.

E. coli K.

Pneumoniae

P.

aeruginosa

P.

fluorescens

S.

aureus

B.

subtilis

S.

pyrogens

A.

janus

P.

glabrum

A.

niger

F.

oxysporum

A.

sclerotiorum

3.109 50 25 50 25 50 50 25 25 25 50 25 25

3.110 50 25 50 25 50 25 25 25 50 50 25 25

3.111 25 12.5 25 12.5 50 25 12.5 25 12.5 25 12.5 12.5

3.112 25 12.5 50 12.5 25 50 12.5 12.5 12.5 25 12.5 25

3.113 12.5 25 25 12.5 25 12.5 25 12.5 12.5 25 12.5 12.5

3.114 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 12.5 25 12.5 12.5

3.115 25 12.5 12.5 12.5 25 12.5 12.5 12.5 12.5 50 12.5 12.5

Amoxicillin 6.25 6.25 6.25 3.12 3.12 6.25 6.25 - - - - -

Fluconazole

- - - - - - - 3.12 3.12 6.25 3.12 3.12

209

Figure-1. In vitro MIC (µg/ml) of bischalcones 3.102-3.108

Figure-2. In vitro MIC (µg/ml) of bispyrazolines 3.109-3.115

It is clear from the Table-3 that compounds 3.104-3.108 exhibited MIC of 12.5 µg/ml

against three gram negative and one gram positive bacterial strains Klubsellia

pneumoniae, Pseudomonas aeruginosa, Pseudomonas fluorescens and Streptoccus

pyrogens respectively. The activity of similar order has been shown by 3.108 against

Pseudomonas aeruginosa, Bacillius subtilis & Streptoccus pyrogens. The compounds

3.105 & 3.107 were also found to be equally active against Bacillius subtilis &

Pseudomonas aeruginosa respectively.

210

The compounds 3.104-3.106 (Table-3) provided significant activity

(MIC-12.5 µg/ml) against the two fungi strains Aspergillius niger & Fusarium

oxysporum. The compounds 3.104 & 3.105 also showed similar behaviour against

Aspergillus sclerotiorum while the compound 3.106 exhibited the noticeable MIC

against Aspergillius janus. The compounds 3.107 and 3.108 significantly inhibited the

growth of strains Pencillium glabrum, Fusarium oxysporum and Pencillium glabrum,

Aspergillius niger respectively.

Regarding the antimicrobial examinations of bispyrazolines (Table-4), the

compounds 3.111, 3.112 and 3.113 showed significant activity (MIC-12.5 µg/ml)

against Pseudomonas fluorescens, Pencillium glabrum and Fusarium oxysporum and

the compounds 3.111 & 3.112 furnished noticeable activity against Klubsellia

pneumoniae and Streptoccus pyrogens. The compound 3.114 and 3.115 had similar

activity against the most of tested bacterial strains. It was observed from Table-4 that

3.113-3.115 were also found to be active (MIC-12.5 µg/ml) against the four fungi

strains namely Aspergillius janus, Pencillium glabrum, Fusarium oxysporum and

Aspergillus sclerotiorum whereas the compound 3.111 could display noticeable

activity against the fungal strain Aspergillus sclerotiorum. The growth of fungi strains

Aspergillius janus, Pencillium glabrum and Fusarium oxysporum was significantly

inhibited by 3.112 at the MIC of 12.5 µg/ml.

The comparison of Table-3 and Table-4 shows that bispyrazolines 3.109-3.115

exhibited the noticeable antibacterial and antifungal properties at MIC of 12.5 µg/ml.

It may be concluded that this study describes the general method for the synthesis of

new bispyrazolines linked through the 3-aryl ring under the normal conditions. The

bispyrazolines seems to be better antimicrobial agents than their corresponding

bischalcones.

211

Experimental

Synthesis of (2E)-1-(4-hydroxyphenyl)-3-(thiophene-2-yl)prop-2-en-1-one 3.101

A mixture of 4-hydroxyacetophenone (4.0 g, 0.02941 mol), 2-thiophenecarboxaldehyde

(3.29 g, 0.02941 mol) and NaOH (1.0 g, 0.024 mol) in ethanol (25.0 ml) was stirred in an

ice bath for 10 hrs. During the course of reaction, the initially formed greenish mixture

changed to a reddish gummy mass. The resulting mixture was poured into iced-HCl to

provide a yellow solid that was filtered, thoroughly washed with water and dried. The

crude substance thus obtained was crystallized from MeOH to obtain a pure solid 3.101.

O

S

OH 4''

1''

2''

3''

12

31'

2 '

3 '

4 '

5 '6 '

5''

3.101

3.101: Yellow needles; Yield 65%; m.p.: 166-168oC. UV-Vis (MeOH) λmax(nm): 336,

238; IR (KBr) cm-1: 3229 (O-H), 1688 (C=O), 1600 (C=C); 1H-NMR (400 MHz, CDCl3):

δ 10.25 (1H, s, OH), 7.96 (1H, d, Jtrans=15.1 Hz, H-3), 7.82 (2H, d, J=3.2 Hz, H-2’, 6’),

7.60 (1H, d, Jtrans=15.1 Hz, H-2), 7.52 (2H, d, J=2.6 Hz, H-3’, 5’), 7.43 (1H, d,

J3’’,4’’ =3.7 Hz, H-3’’), 7.12 (1H, d, J5’’,4’’ =4.8 Hz, H-5’’), 6.89 (1H, d, J4’’,3’’ =3.7 Hz,

H-4’’); MS(ESI): m/z (M)+ 230 (70%). Anal. Calc. for C13H10O2S: C, 67.82 %;

H, 4.34 %; S, 13.91 %; Found: C, 67.70 %; H, 4.30 %; S, 13.86 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(propane-1,3-diylbis(oxy))bis(4,1-phenylene))bis(3-

(thiophen-2-yl)prop-2-en-1-one 3.102

A suspension of chalcone 3.101 (2.0 g, 0.0086957 mol), anhydrous K2CO3 (2.0 g),

1,3-dibromopropane (0.87 g, 0.00434783 mol), tetra butyl ammonium iodide (1.0 g) in

dry acetone (25.0 ml) was refluxed for 6 hrs with continuous stirring. The progress of

reaction was monitored by TLC. After the completion of reaction, the reaction mixture

turned to a colourless mass which was poured over iced-HCl to obtain a solid. The crude

product thus obtained was crystallized from CHCl3:MeOH (1:1) to yield pure compound

3.102.

212

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 CH2 CH2 O

OS

3.102


IR (KBr) cm-1 2923, 2870 (methylene C-H), 1660 (C=O), 1596 (C=C), 1236, 1034

(C-O); 1H-NMR (400 MHz, CDCl3): δ 8.00 (4H, d, Jo=8.5 Hz, H-2’, 6’), 7.84 (2H, d,

Jtrans=14.5 Hz, H-3), 7.51 (2H, d, J5’’,4’’ =4.9 Hz, H-5’’), 7.43 (4H, m, H-2, 3’’),

7.13 (2H, d, J4’’,3’’ =3.8 Hz, H-4’’), 7.03 (4H, d, Jo=8.5 Hz, H-3’, 5’), 4.29 (4H, t,

Jvic=5.8 Hz, OCH2CH2), 2.08 (2H, t, Jvic=5.8 Hz, OCH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 186.60 (C=O), 162.48 (C-4’), 139.80 (C-3), 135.73 (C-2’’), 131.94 (C-1’),

130.48 (C-2’, 6’), 130.25 (C-5’’), 129.32 (C-3’’), 128.20 (C-4’’), 120.10 (C-2), 114.10

(C-3’, 5’), 67.28 (OCH2CH2), 25.20 (OCH2CH2); MS(ESI): m/z 501 (M+1, 9%), 436

(19%), 411 (22%), 394 (8%), 393 (42%), 375 (11%), 339 (41%), 335 (14%), 307 (86%),

281 (28%), 182 (71%), 134 (74%), 106 (33%). Anal. Calc. for C29O4H24S2: Calc.

C, 69.60 %; H, 4.80 %; S, 12.80 %; Found: C, 69.87 %; H, 4.83 %; S, 12.85 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(3-


The compound 3.103 was obtained by reacting 3.101 (2.0 g, 0.0086957 mol) with

1,4-dibromobutane (0.93 g, 0.00434783 mol) under similar conditions as described

earlier for 3.102.

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)2 CH2 O

OS

3.103




Jtrans=15.2 Hz, H-3), 7.61 (2H, d, J5’’,4’’ =5.0 Hz, H-5’’), 7.52 (2H, d, J3’’,4’’ =3.7 Hz,

213

H-3’’), 7.45 (2H, d, Jtrans=15.2 Hz, H-2), 7.11 (2H, dd, J4’’,3’’ =3.7 Hz, J4’’,5’’ =5.0 Hz,

H-4’’), 7.01 (4H, d, Jo=8.8 Hz, H-3’, 5’), 4.14 (4H, t, Jvic=5.8 Hz, OCH2CH2), 1.96

(4H, quintet, Jvic=5.8 Hz, OCH2CH2); 13C-NMR (100 MHz, CDCl3): δ 186.65 (C=O),

162.45 (C-4’), 139.84 (C-3), 135.69 (C-2’’), 131.90 (C-1’), 130.46 (C-2’, 6’), 130.21

(C-5’’), 129.27 (C-3’’), 128.28 (C-4’’), 120.13 (C-2), 114.17 (C-3’, 5’), 67.37

(OCH2CH2), 25.26 (OCH2CH2); MS(ESI): m/z 515 (M+1, 6%), 448 (100%), 447 (3%),

425 (6%), 406 (76%), 405 (44%), 387 (30%), 353 (34%), 349 (18%), 321 (87%), 295

(92%), 196 (25%), 148 (38%), 120 (28%). Anal. Calc. for C30O4H26S2: Calc. C, 70.03 %;

H, 5.05 %; S, 12.45 %; Found: C, 70.31 %; H, 5.03 %; S, 12.49 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(pentane-1,5-diylbis(oxy))bis(4,1-phenylene))bis(3-


The compound 3.104 was synthesized by treating 3.101 (2.0 g, 0.0086957 mol) with

1,5-dibromopentane (0.99 g, 0.00434783 mol) under the similar conditions as used for

3.102.

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)3 CH2 O

OS

3.104






H-4’’), 7.00 (4H, d, Jo=8.2 Hz, H-3’, 5’), 4.11 (4H, t, Jvic=6.2 Hz, OCH2CH2CH2), 1.92

(4H, quintet, Jvic=6.2 Hz, OCH2CH2CH2), 1.64 (2H, quintet, Jvic=6.2 Hz, CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 186.68 (C=O), 162.47 (C-4’), 139.80 (C-3), 135.63

(C-2’’), 131.95 (C-1’), 130.49 (C-2’, 6’), 130.24 (C-5’’), 129.29 (C-3’’), 128.22 (C-4’’),

120.15 (C-2), 114.12 (C-3’, 5’), 67.39 (OCH2CH2CH2), 25.28 (OCH2CH2CH2), 25.19

(CH2CH2CH2); MS(ESI): m/z 551 (M+Na, 24%), 462 (9%), 461 (48%), 439 (87%), 420

(44%), 419 (57%), 401 (60%), 367 (31%), 363 (7%), 335 (100%), 309 (28%), 210 (22%),

214

162 (17%), 148 (90%). Anal. Calc. for C31O4H28S2: Calc. C, 70.45 %; H, 5.30 %;

S, 12.12 %, Found: C, 70.17 %; H, 5.28 %; S, 12.16 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(hexane-1,6-diylbis(oxy))bis(4,1-phenylene))bis(3-


The compound 3.105 was prepared by reacting 3.101 (2.0 g, 0.0086957 mol) with

1,6-dibromohexane (1.1 g, 0.00434783 mol) under the similar conditions as described

above for 3.102.

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)4 CH2 O

OS

3.105






H-4’’), 6.97 (4H, d, Jo=8.8 Hz, H-3’, 5’), 4.06 (4H, t, Jvic=6.4 Hz, OCH2CH2CH2), 1.87

(4H, quintet, Jvic=6.4 Hz, OCH2CH2CH2), 1.58 (4H, quintet, Jvic=6.4 Hz, CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 186.69 (C=O), 162.26 (C-4’), 140.68 (C-3), 136.47

(C-2’’), 131.86 (C-1’), 130.23 (C-5’’), 130.39 (C-2’, 6’), 128.51 (C-3’’), 128.38 (C-4’’),

120.27 (C-2), 114.37 (C-3’, 5’), 67.83 (OCH2CH2CH2), 29.13 (OCH2CH2CH2), 25.90

(CH2CH2CH2); MS(ESI): m/z 581 (M+K, 3%), 566 (M+Na+1, 21%), 565 (M+Na, 53%),

543 (M+1, 45%), 476 (4%), 475 (13%), 453 (14%), 434 (26%), 433 (100%), 415 (20%),

381 (7%), 359 (17%), 358 (19%), 331 (13%), 313 (4%), 257 (5%), 249 (6%), 231 (22%),

210 (2%), 149 (7%). Anal. Calc. for C32O4H30S2: Calc. C, 70.84 %; H, 5.53 %; S, 11.80;

Found: C, 71.12 %; H, 5.51 %; S, 11.76 %.

215



The compound 3.106 was obtained from the reaction of 3.101 (2.0 g, 0.0086957 mol)

with 1,8-dibromooctane (1.2 g, 0.00434783) under the similar conditions as used earlier

for 3.102.

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)6 CH2 O

OS

3.106




Jtrans=14.9 Hz, H-3), 7.52 (2H, d, J5’’,4’’ =4.5 Hz, H-5’’), 7.45 (4H, m, H-2, 3’’), 7.12

(2H, d, J4’’,5’’ =4.5 Hz, H-4’’), 6.98 (4H, d, J=8.6 Hz, H-3’, 5’), 4.02 (4H, t, Jvic=6.6 Hz,

OCH2CH2CH2CH2), 1.81 (4H, quintet, Jvic=6.6 Hz, OCH2CH2CH2CH2), 1.42 (8H, m,

CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 186.60 (C=O), 162.56 (C-4’), 139.82

(C-3), 135.64 (C-2’’), 131.49 (C-1’), 130.24 (C-2’, 6’), 130.05 (C-5’’), 128.63 (C-3’’),

128.05 (C-4’’), 120.05 (C-2), 113.96 (C-3’, 5’), 67.70 (OCH2CH2CH2CH2), 28.65

(OCH2CH2CH2CH2), 28.49 (OCH2CH2CH2CH2), 25.34 (OCH2CH2CH2CH2); MS(ESI):

m/z 610 (M+K+1, 2%), 609 (M+K, 9%), 594 (M+Na+1, 19%), 593 (M+Na, 46%), 571

(M+1, 100%), 500 (3%), 499 (9%), 475 (21%), 462 (27%), 461 (100%), 453 (29%), 443

(13%), 435 (10%), 386 (22%), 341 (27%), 325 (7%), 304 (10%), 231 (28%), 213 (6%),

202 (3%), 149 (17%), 137 (43%); Anal. Calc. for C34O4H34S2: Calc. C, 71.57 %;

H, 5.96 %; S, 11.22 %; Found: C, 71.85 %; H, 5.94 %; S, 11.26 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(decane-1,10-diylbis(oxy))bis(4,1-phenylene))bis(3-


The bischalcone 3.107 was synthesized by reacting 3.101 (2.0 g, 0.0086957 mol) with

1,10-dibromodecane (1.30 g, 0.00434783 mol) under the similar conditions as described

above for 3.102.

216

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)8 CH2 O

OS

3.107



(C-O); 1H-NMR (400 MHz, CDCl3): δ 8.00 (4H, d, Jo=8.4 Hz, H-2’, 6’), 7.94 (4H, m,

H-3, 5’’), 7.53 (2H, d, J3’’,4’’ =3.8 Hz, H-3’’), 7.43 (2H, d, Jtrans=15.0 Hz, H-2), 7.12

(2H, d, J4’’,5’’ =5.0 Hz, H-4’’), 6.98 (4H, d, Jo=8.4 Hz, H-3’,5’), 4.06 (4H, t, Jvic=6.1 Hz,


(12H, m, CH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 186.66 (C=O), 162.50

(C-4’), 139.80 (C-3), 135.67 (C-2’’), 131.50 (C-1’), 130.26 (C-2’, 6’), 130.15 (C-5’’),

128.69 (C-3’’), 128.09 (C-4’’), 120.23 (C-2), 113.99 (C-3’, 5’), 67.56



(OCH2CH2CH2CH2CH2); MS(ESI): m/z 621 (M+Na, 98%), 600 (M+2, 24%), 599

(M+1, 72%), 577 (2%), 573 (6%), 558 (3%), 557 (7%), 543 (4%), 529 (9%), 528 (34%),

527 (92%), 525 (3%), 507 (4%), 506 (6%), 505 (23%), 497 (4%), 490 (7%), 489 (29%),

475 (27%), 453 (20%), 415 (4%), 414 (22%), 380 (13%), 354 (8%), 353 (19%), 337

(21%), 304 (26%), 275 (51%), 257 (100%), 241 (16%), 215 (12%). Anal. Calc. for

C36O4H38S2: Calc. C, 72.24 %; H, 6.35 %; S; 10.70 %; Found: C, 71.96 %; H, 6.33 %;

S, 10.74 %.

Synthesis of (2E,2’E)-1,1’-(4,4’-(dodecane-1,12-diylbis(oxy))bis(4,1-

phenylene))bis(3-(thiophen-2-yl)prop-2-en-1-one 3.108

The bischalcone 3.108 was prepared by treating 3.101 (2.0 g, 0.0086957 mol) with

1,12-dibromododecane (1.42 g, 0.004347 mol) under the similar conditions as used

earlier for 3.102.

217

3''4''

5'' 6'2''

1''

4'

5'

3'2'

1'12

3S O

O CH2 (CH2)10 CH2 O

OS

3.108




Jtrans=15.3 Hz, H-3), 7.40 (2H, d, J5’’,4’’ =5.0 Hz, H-5’’), 7.36 (2H, d, Jtrans=15.3 Hz, H-2),

7.33 (2H, d, J3’’,4’’ =3.7 Hz, H-3’’), 7.08 (2H, dd, J4’’,3’’ =3.7, J4’’,5’’ =5.1 Hz, H-4’’), 6.96

(4H, d, Jo=8.8 Hz, H-3’, 5’), 4.03 (4H, t, Jvic=6.5 Hz, OCH2CH2CH2CH2CH2CH2), 1.81

(4H, quintet, Jvic=6.5 Hz, OCH2CH2CH2CH2CH2CH2), 1.47 (4H, quintet, Jvic=5.6 Hz,

CH2CH2CH2CH2CH2CH2), 1.33 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 186.86 (C=O), 162.44 (C-4’), 139.78 (C-3), 135.57 (C-2’’), 131.61

(C-1’), 130.22 (C-2’, 6’), 130.19 (C-5’’), 128.79 (C-3’’), 128.29 (C-4’’), 120.33 (C-2),

113.66 (C-3’, 5’), 67.78 (OCH2CH2CH2CH2CH2CH2), 29.64



(OCH2CH2CH2CH2CH2CH2); MS(ESI): m/z 665 (M+K, 16%), 649 (M+Na, 12%), 627

(M+1, 13%), 626 (M, 22%), 613 (9%), 612 (22%), 608 (14%), 595 (6%), 594 (12%), 572

(5%), 571 (14%), 563 (8%), 555 (11%), 547 (7%), 533 (2%), 525 (8%), 497 (6%), 496

(13%), 495 (32%), 479 (33%), 442 (100%), 415 (6%), 397 (5%), 332 (11%), 286 (6%).

Anal. Calc. for C38O4S2H42: Calc. C, 72.84 %; H, 6.70 %; S, 10.22 %; Found:

C, 73.13 %; H, 6.72 %; S, 10.26 %.

Synthesis of 1,3-bis[3-(4-phenyl)-4,5-dihydro-1-phenyl-5-(thiophen-2-yl)-1H-

pyrazole] propane 3.109

A mixture of 3.102 (1.0 g, 0.001929 mol), phenyl hydrazine (0.42 g, 0.0038839 mol) and

glacial acetic acid (5 ml) in dry EtOH (30 ml) was refluxed for 8 hrs. The progress of

reaction was monitored by TLC. The resulting reaction mixture was concentrated under

vacuum to obtain a solid substance which was further crystallized from MeOH to yield a

pure compound 3.109.

218

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 CH2 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.109


IR (KBr) cm-1 2945, 2840 (methylene C-H), 1593 (C=N), 1242, 1025 (C-O); 1H-NMR

(400 MHz, CDCl3): δ 7.63 (4H, d, Jo=8.6 Hz, H-2’’’, 6’’’), 7.33 (2H, d, J3’’,4’’ =3.7 Hz,

H-3’’), 7.22 (2H, d, J5’’,4’’ =5.0 Hz, H-5’’), 7.12 (6H, m, H-3’, 4’, 5’), 6.99 (4H, d,

Jo=8.6 Hz, H-3’’’, 5’’’), 6.89 (2H, dd, J4’’,3’’ =3.7 Hz, J4’’,5’’ =5.0 Hz, H-4’’), 6.70 (4H, t,

Jo=7.2 Hz, H-2’, 6’), 5.60 (2H, dd, JXA=6.2 Hz, JXM=11.8 Hz, HX), 4.02 (4H, t,

Jvic=5.8 Hz, OCH2CH2), 3.82 (2H, dd, JMX=11.8 Hz, JMA=17.2 Hz, HM), 3.19 (2H, dd,

JAX=6.2 Hz, JAM=17.2 Hz, HA), 2.50 (2H, quintet, Jvic=5.8 Hz, OCH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 160.15 (C-4’’’), 154.26 (C-3), 147.34 (C-2’’), 145.15 (C-1’),

144.87 (C-1’’’), 128.03 (C-5’’), 127.55 (C-3’’), 126.30 (C-2’’’, 6’’’), 126.26 (C-4’’),

124.68 (C-3’, 5’), 118.60 (C-4’), 114.90 (C-3’’’, 5’’’), 113.77 (C-2’, 6’), 67.10

(OCH2CH2), 59.41 (C-5), 43.39 (C-4), 24.47 (OCH2CH2); MS(ESI): m/z 703

(M+Na, 7%), 614 (80%), 420 (33%), 377 (53%), 303 (25%), 297 (62%), 221 (89%), 220

(17%), 145 (10%). Anal. Calc. for C41O2N4H36S2: Calc. C, 72.35 %; H, 5.29 %;

N, 8.20 %; S, 9.41 %; Found: C, 72.63 %; H, 5.27 %; N, 8.23 %; S, 9.38 %.


pyrazole] butane 3.110


0.00195 mol) with phenyl hydrazine (0.42 g, 0.0039 mol) under the similar conditions as

described above for 3.109.

219

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)2 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.110




H-3’’), 7.17 (2H, d, J5’’,4’’ =5.0 Hz, H-5’’), 7.09 (6H, m, H-3’, 4’, 5’), 6.95 (4H, d,


Jo=7.2 Hz, H-2’, 6’), 5.67 (2H, dd, JXA=6.2 Hz, JXM=11.8 Hz, HX), 4.09 (4H, brs,

OCH2CH2), 3.86 (2H, dd, JMX=11.8 Hz, JMA=17.2 Hz, HM), 3.21 (2H, dd,

JAX=6.2 Hz, JAM=17.2 Hz, HA), 2.52 (4H, brs, OCH2CH2); 13C-NMR (100 MHz, CDCl3):

δ 160.12 (C-4’’’), 155.56 (C-3), 147.50 (C-2’’), 145.85 (C-1’), 144.77 (C-1’’’), 128.53

(C-5’’), 127.15 (C-3’’), 126.78 (C-2’’’, 6’’’), 126.66 (C-4’’), 124.48 (C-3’, 5’), 118.70

(C-4’), 114.40 (C-3’’’, 5’’’), 113.27 (C-2’, 6’), 67.13 (OCH2CH2), 59.47 (C-5), 43.41

(C-4), 25.37 (OCH2CH2); MS(ESI): m/z 717 (M+Na, 14%), 691 (100%), 675 (39%), 674

(11%), 673 (28%), 627 (8%), 612 (32%), 600 (83%), 511 (75%), 495 (57%), 332 (5%),

310 (8%), 276 (16%), 222 (72%), 145 (53%). Anal. Calc. for C42O2N4H38S2: Calc.

C, 72.62 %; H, 5.47 %; N, 8.07 %; S, 9.22 %; Found: C, 72.91 %; H, 5.49 %; N, 8.10 %;

S, 9.25 %.


pyrazole] pentane 3.111


0.00189 mol) with phenyl hydrazine (0.40 g, 0.00378 mol) under the same conditions as


220

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)3 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.111




H-3’’), 7.19 (2H, d, J5’’,4’’ =5.0 Hz, H-5’’), 7.02 (6H, m, H-3’, 4’, 5’), 6.92 (4H, d,



Jvic=6.0 Hz, OCH2CH2CH2), 3.81 (2H, dd, JMX=11.8 Hz, JMA=17.2 Hz, HM), 3.24

(2H, dd, JAX=6.2 Hz, JAM=17.2 Hz, HA), 2.32 (4H, quintet, Jvic=6.0 Hz, OCH2CH2CH2),

1.58 (2H, m, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 160.19 (C-4’’’), 155.50

(C-3), 147.67 (C-2’’), 145.80 (C-1’), 144.70 (C-1’’’), 128.59 (C-5’’), 127.19 (C-3’’),

126.67 (C-2’’’, 6’’’), 126.60 (C-4’’), 124.03 (C-3’, 5’), 118.79 (C-4’), 114.48

(C-3’’’, 5’’’), 113.45 (C-2’, 6’), 67.10 (OCH2CH2CH2), 59.49 (C-5), 43.47 (C-4), 28.39

(OCH2CH2CH2), 25.67 (OCH2CH2CH2); MS(ESI): m/z 709 (M+1, 4%), 705 (7%), 689

(16%), 688 (28%), 687 (31%), 666 (93%), 665 (80%), 641 (3%), 637 (54%), 626 (90%),

625 (39%), 614 (29%), 525 (56%), 509 (47%), 453 (62%), 421 (42%), 346 (70%), 324

(36%), 290 (53%), 236 (71%), 235 (65%), 159 (50%). Anal. Calc. for C43O2N4H40S2:

Calc. C, 72.88 %; H, 5.64 %; N, 7.90 %; S, 9.03 %; Found: C, 72.59 %; H, 5.62 %;

N, 7.93 %; S, 9.05 %.


pyrazole] hexane 3.112

The compound 3.112 was obtained by treating bischalcone 3.105 (1.0 g, 0.00185 mol)

with phenyl hydrazine (0.39 g, 0.00370 mol) under the similar conditions as described

above for 3.109.

221

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)4 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.112



(400 MHz, CDCl3): δ 7.66 (4H, d, Jo=8.8 Hz, H-2’’’,6’’’), 7.40 (2H, d, J3’’,4’’ =3.8 Hz,

H-3’’), 7.24 (2H, d, J5’’,4’’ =5.2 Hz, H-5’’), 7.10 (6H, m, H-3’, 4’, 5’), 6.93 (2H, dd,

J4’’,3’’ =3.8 Hz, J4’’,5’’ =5.2 Hz, H-4’’), 6.88 (4H, d, Jo=8.8 Hz, H-3’’’, 5’’’), 6.73 (4H, t,


Jvic=6.0 Hz, OCH2CH2CH2), 3.85 (2H, dd, JMX=12.2 Hz, JMA=17.4 Hz, HM), 3.23

(2H, dd, JAX=6.7 Hz, JAM=17.4 Hz, HA), 1.56 (4H, quintet, Jvic=6.0 Hz, OCH2CH2CH2),

1.51 (4H, quintet, Jvic=6.0 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 160.39

(C-4’’’), 155.58 (C-3), 147.73 (C-2’’), 145.95 (C-1’), 144.86 (C-1’’’), 128.78 (C-5’’),

127.14 (C-3’’), 126.69 (C-4’’), 126.43 (C-2’’’, 6’’’), 124.60 (C-3’, 5’), 118.91 (C-4’),

114.62 (C-3’’’, 5’’’), 113.48 (C-2’, 6’), 67.23 (OCH2CH2CH2), 59.59 (C-5), 43.50 (C-4),

28.43 (OCH2CH2CH2), 25.70 (OCH2CH2CH2); MS(ESI): m/z 723 (M+1, 18%), 722

(M, 22%), 721 (100%), 719 (19%), 703 (3%), 702 (9%), 701 (23%), 681 (4%), 680

(15%), 679 (30%), 655 (5%), 640 (2%), 639 (8%), 637 (13%), 633 (17%), 628 (8%), 539

(5%), 523 (10%), 475 (18%), 453 (22%), 435 (12%), 419 (7%), 360 (6%), 338 (13%),

304 (11%), 250 (14%), 249 (17%), 236 (12%), 173 (8%). Anal. Calc. for C44O2N4H42S2:

Calc. C, 73.13 %; H, 5.82 %; N, 7.76 %; S, 8.86 %; Found: C, 72.83 %; H, 5.84 %;

N, 7.73 %; S, 8.89 %.


pyrazole] octane 3.113


0.00175 mol) with phenyl hydrazine (0.37 g, 0.0035 mol) under similar conditions as

used above for 3.109.

222

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)6 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.113




H-3’’), 7.23 (2H, d, J5’’,4’’ =4.9 Hz, H-5’’), 7.10 (6H, m, H-3’, 4’, 5’), 6.92 (2H, dd,

J4’’,3’’ =3.8 Hz, J4’’,5’’ =4.9 Hz, H-4’’), 6.86 (4H, d, Jo=8.2 Hz, H-3’’’, 5’’’), 6.74 (4H, t,


Jvic=6.1 Hz, OCH2CH2CH2CH2), 3.83 (2H, dd, JMX=12.2 Hz, JMA=16.5 Hz, HM), 3.22

(2H, dd, JAX=6.8 Hz, JAM=16.5 Hz, HA), 1.78 (4H, quintet, Jvic=6.1 Hz,

OCH2CH2CH2CH2), 1.48 (4H, quintet, Jvic=6.1 Hz, OCH2CH2CH2CH2), 1.41 (4H, m,

OCH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 160.50 (C-4’’’), 155.78 (C-3),

147.71 (C-2’’), 145.90 (C-1’), 144.80 (C-1’’’), 128.56 (C-5’’), 127.11 (C-3’’), 126.60

(C-4’’), 126.48 (C-2’’’, 6’’’), 124.59 (C-3’, 5’), 118.99 (C-4’), 114.69 (C-3’’’, 5’’’),

113.50 (C-2’, 6’), 67.45 (OCH2CH2CH2CH2), 59.74 (C-5), 43.62 (C-4), 28.49

(OCH2CH2CH2CH2), 25.79 (OCH2CH2CH2CH2), 25.19 (OCH2CH2CH2CH2); MS(ESI):

m/z 752 (M+2, 7%), 750 (M, 23%), 747 (53%), 702 (4%), 701 (12%), 659 (13%), 658

(4%), 568 (6%), 567 (9%), 565 (13%), 551 (8%), 489 (5%), 476 (3%), 475 (23%), 453

(17%), 429 (24%), 257 (100%). Anal. Calc. for C46O2N4H46S2: Calc. C, 73.60 %;

H, 6.13 %; N, 7.46 %; S, 8.53 %; Found: C, 73.89 %; H, 6.15 %; N, 7.43 %; S, 8.49 %.


pyrazole] decane 3.114


0.00167 mol) with phenyl hydrazine (0.36 g, 0.00334 mol) under similar conditions as

used earlier for 3.109.

223

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)8 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.114




H-3’’), 7.19 (2H, d, J5’’,4’’ =5.2 Hz, H-5’’), 7.10 (6H, m, H-3’, 4’, 5’), 6.94 (2H, dd,

J4’’,3’’ =3.6 Hz, J4’’,5’’ =5.2 Hz, H-4’’), 6.92 (4H, d, Jo=8.7 Hz, H-3’’’,5’’’), 6.75 (4H, t,


Jvic=6.3 Hz, OCH2CH2CH2CH2CH2), 3.82 (2H, dd, JMX=11.8 Hz, JMA=17.0 Hz, HM),

3.20 (2H, dd, JAX=6.9 Hz, JAM=17.0 Hz, HA), 1.79 (4H, quintet, Jvic=6.3 Hz,


(8H, m, OCH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 159.35 (C-4’’’),

156.23 (C-3), 145.79 (C-1’), 145.62 (C-2’’), 144.88 (C-1’’’), 128.38 (C-5’’), 126.90

(C-3’’), 126.43 (C-4’’), 125.61 (C-2’’’, 6’’’), 124.46 (C-3’, 5’), 118.74 (C-4’), 114.15

(C-2’, 6’), 113.19 (C-3’’’, 5’’’), 67.47 (OCH2CH2CH2CH2CH2), 59.73 (C-5), 43.54

(C-4), 28.84 (OCH2CH2CH2CH2CH2), 28.72 (OCH2CH2CH2CH2CH2), 28.61

(OCH2CH2CH2CH2CH2), 25.42 (OCH2CH2CH2CH2CH2); MS(ESI): m/z 779

(M+1, 38%), 778 (M, 42%), 777 (98%), 775 (100%), 773 (4%), 721 (3%), 719 (13%),

689 (21%), 679 (19%), 624 (6%), 623 (13%), 596 (12%), 595 (15%), 593 (28%), 577

(27%), 576 (3%), 517 (2%), 489 (3%), 476 (4%), 475 (27%), 453 (38%), 435 (17%), 395

(2%), 359 (5%), 358 (21%), 320 (13%), 304 (11%), 282 (12%). Anal. Calc. for

C48O2N4H50S2: Calc. C, 74.03 %; H, 6.42 %; N, 7.20 %; S, 8.22 %; Found: C, 74.32 %;

H, 6.39 %; N, 7.22 %; S, 8.25 %.

224


pyrazole] dodecane 3.115


0.0016 mol) with phenyl hydrazine (0.34 g, 0.0032 mol) under the similar conditions as

described above for 3.109.

1''

2''

3''4''

5''

4'

1'2'

3'

6'

5'

1

2

34

5

1'''

2'''3'''

4'''

5'''

6'''

SN

N

O CH2 (CH2)10 CH2 O

NN

S

HMHA

HX

HM

HA

HX

3.115

3.115: Orange solid; Yield 63%; m.p.: 110-112oC. UV-Vis (MeOH) λmax(nm): 355, 248;



H-3’’), 7.16 (2H, d, J5’’,4’’ =5.2 Hz, H-5’’), 7.04 (6H, m, H-3’, 4’, 5’), 6.98 (4H, d,



Jvic=6.4 Hz, OCH2CH2CH2CH2CH2CH2), 3.84 (2H, dd, JMX=11.8 Hz, JMA=17.2 Hz, HM),

3.21 (2H, dd, JAX=6.6 Hz, JAM=17.2 Hz, HA), 1.78 (4H, quintet, Jvic=6.4 Hz,

OCH2CH2CH2CH2CH2CH2), 1.45 (4H, quintet, Jvic=6.4 Hz, OCH2CH2CH2CH2CH2CH2),

1.30 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 160.45

(C-4’’’), 155.42 (C-3), 145.78 (C-1’), 145.53 (C-2’’), 144.79 (C-1’’’), 128.43 (C-5’’),

126.98 (C-3’’), 126.58 (C-4’’), 124.61 (C-2’’’, 6’’’), 124.16 (C-3’, 5’), 118.70 (C-4’),

114.22 (C-2’, 6’), 113.21 (C-3’’’, 5’’’), 67.38 (OCH2CH2CH2CH2CH2CH2), 59.62 (C-5),

43.25 (C-4), 28.94 (OCH2CH2CH2 CH2CH2CH2), 28.77 (OCH2CH2CH2CH2CH2CH2),

28.42 (OCH2CH2CH2CH2CH2CH2), 28.02 (OCH2CH2CH2CH2CH2CH2), 25.45

(OCH2CH2CH2CH2CH2CH2); MS(ESI): m/z 829 (M+Na, 68%), 805 (20%), 803 (49%),

801 (38%), 751 (50%), 749 (68%), 717 (8%), 707 (25%), 652 (55%), 651 (90%), 624

(69%), 604 (71%), 504 (33%), 481 (26%), 463 (8%), 423 (19%), 387 (3%), 386 (40%),

225

348 (56%), 332 (7%), 310 (13%). Anal. Calc. for C50O2N4H54S2: Calc. C, 74.44 %;

H, 6.70 %; N, 6.95 %; S, 7.94 %; Found: C, 74.14 %; H, 6.72 %; N, 6.97 %; S, 7.97 %.

226

References

1. Xia, Y.; Fan, C.-D.; Zhao, B.-X.; Zhao, J.; Shin, D.-S. and Miao, J.-Y. Eur. J. Med.

Chem. 2008, 43, 2347.

2. Levai, L. and Jeko, J. Acta Chim. Slov. 2009, 56, 566.

3. Abdel-Aziz, M.; Abuo-Rahma, G. E.-D. A. and Hassan, A. A. Eur. J. Med. Chem.

2009, 44, 3480.

4. Das, B. C.; Bhowmik, D.; Chiranjit, B. and Mariappan, G. J. Pharm. Res. 2010,

3(6), 1345.

5. Azarifar, D. and Khosravi, K. J. Chin. Chem. Soc. 2009, 56, 43.

6. (a) Gennari, C. Comprehensive Organic Synthesis, Trost, B. M. and Fleming, I.

(Eds.), Pergamon, Oxford, UK, 1991, 2, 629; (b) Mahrwald, R. Modern Aldol

Reactions; Wiley-VCH, Weinheim, Germany, 2004 1-2; (c) Mukaiyama, T.

Organic Reactions; Dauben, W. G. (Ed.) J. Wiley & Sons: New York, NY,

USA, 1982, 28, 203; (d) Healthcock, C. H. Comprehensive Organic Synthesis

Trost, B. M.; Fleming, I. (Eds.), Pergamon, Oxford, UK, 1991, 2, 133.


227

Chapter-IIIc Synthesis of new 1,3,5-triphenyl-


� New bispyrazoline derivatives built around aliphatic chains: synthesis,

characterization and antimicrobial studies


Journal of Chemical Sciences (Accepted manuscript, Ms No. JCSC- D-12-

00021R1).

228

The synthesis of bisheterocyclic compounds have been the subject of significant

attraction for the organic chemists in the past.1-8 These substrates are important from

the synthetic, structural and biological point of view. In the earlier chapters (IIIa &

IIIb ), the researchers were focussed upon the synthesis of bispyrazolines linked via

3-aryl ring. It would be advantageous here to explore the synthesis and

characterization studies of new bispyrazolines linked via 5-aryl ring with aliphatic

chains of varying lengths. The syntheses of these compounds have been planned

starting from dibenzaldehydes. The major interest in this study was to investigate the

utility of dibenzaldehyde for the preparation of new bisheterocyclic products

3.124-3.131.

The bispyrazolines 3.124-3.131 needed for the present study was prepared from the

cyclization reaction of bischalcones 3.116-3.123 with phenyl hydrazine by refluxing

under alcoholic medium in the presence of glacial acetic acid. The bischalcones were

obtained from the Claisen-Schmidt reaction9 of acetophenone with dibenzaldehydes

2.48-2.55. The structures of the prepared compounds were determined from the

rigorous analysis of their spectral data (UV-Vis, IR, 1H-NMR, 13C-NMR & ESI-MS).

The elemental analysis also confirmed the purity of these compounds.

NN HX

HM

HA

O CH2 (CH2)n CH2 O NNHX

HA

HM

3.124-3.131

n = 0, 1, 2, 3, 4, 6, 8, 10




The dibenzaldehyde 2.48 was reacted with acetophenone in the presence of

NaOH/EtOH at room temperature for 12 hrs and the decomposition of resulting

reaction mixture into iced-HCl provided a solid product (Scheme-3.34). The crude

229

substance thus obtained was purified by crystallization in CHCl3:MeOH (1:1) to

furnish pure compound 3.116 as a brown solid (64%, m.p. 102-104°C).

2.48

1'

2'3'

4'

5'6'

1''

2'' 3''

4''

5''6''

12

3

NaOH/EtOH/

O CH2 CH2 O C

O

HC

O

H

O CH2

O

CH2 O

O3.116

Ph C CH3

O

Scheme-3.34

The structure of 3.116 became evident from its spectroscopic data. Its IR spectrum

exhibited major absorptions at 2964, 2856 (methylene C-H), 1657 (C=O) and 1602

(C=C). Its UV-Vis spectrum had two maxima at 328 and 250 nm which may be

assigned to n→π* & π→π* transitions respectively.

In the 1H-NMR spectrum (400 MHz, CDCl3) of 3.116, aromatic protons (H-2’, 6’ &

3’, 4’, 5’) produced well defined signals at δ 8.01 (4H, dd, Jp,o=1.1, 8.8 Hz) and 7.52

(6H, m) respectively. The downfield resonance of former as compared to later protons

could be ascribed to its proximity to the C=O group. In this region, two broad

doublets centred at δ 7.73 (2H, Jtrans=15.6 Hz) and 7.39 (2H, Jtrans=15.6 Hz) were

represented by trans protons H-3 and H-2 respectively. Regarding the remaining

signals in the aromatic region, two triplet of doublets integrating for four hydrogens

each at δ 7.42 (Jp,o=1.1, 8.8 Hz) and 6.90 (Jp,o=1.1, 8.8 Hz) could be easily ascribed to

H-2’’, 6’’ and H-3’’, 5’’ respectively. A singlet at δ 4.01 (4H) may be provided by

internal chain OCH2 protons.

The ESI-MS spectrum of 3.116 exhibited heaviest ion at m/z 475 (M+1, 100%) and

other significant peaks were observed at m/z 334 (3%), 333 (78%), 332 (23%), 311

(37%), 310 (59%), 304 (38%), 293 (63%), 174 (8%) and 74 (9%). Its mass

fragmentation was found to be similar as shown in Chart-1 (vide experimental). 13C-NMR (100 MHz, CDCl3) spectrum of 3.116 was very helpful to corroborate its

proposed structure which confirmed the presence of C=O group by the appearance of

a downfield signal at δ 190.22. The carbon atoms C-4’’, C-3 and C-2 were located at

230

δ 160.98, 144.62 and 119.90 respectively. The remaining signals in the aromatic

region were found to be present at δ 138.40 (C-1’), 130.22 (C-2’, 6’), 127.71 (C-1’’),

128.50 (C-2’’, 6’’), 138.50 (C-4’), 128.44 (C-3’, 5’) and 114.95 (C-3’’, 5’’). The

OCH2 group of the intervening chain also furnished a suitable signal at δ 64.20.


The compound 3.116 was refluxed with phenyl hydrazine in dry EtOH/AcOH

medium and cooling of the resulting reaction mixture in an ice bath yielded a solid

product (Scheme-3.35) which was crystallized from MeOH to yield pure compound

3.124 (70%, m.p. 90-92°C).

1'

2

2'

3

3'

4

4'

5

5'6'

1

1''

2'' 3''

4''

5''6''

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

12

3

EtOH/AcOH/ PhNHNH2/ ∆

O CH2

O

CH2 O

O

NN HX

HM

HA

O CH2 CH2 O NNHX

HA

HM

3.116

3.124

Scheme-3.35 IR spectrum of 3.124 displayed a significant band at 1590 cm-1 due to the C=N

moiety of the pyrazoline ring. Its 1H-NMR spectrum (400 MHz, DMSO-d6), showed

the signals of the aromatic protons H-2’’, 6’’ & H-3’’, 4’’, 5’’ at δ 7.67 (4H, dd,

Jp,o=1.1, 8.8 Hz) and 7.36 (6H, m) respectively. The phenyl ring (C-5) protons

furnished a doublet of doublet each at δ 7.12 (4H, Jp,o=1.1, 8.8 Hz, H-2’’’, 6’’’) and

6.80 (4H, Jp,o=1.1, 8.8 Hz, H-3’’’, 5’’’). The hydrogens belonging to the N-phenyl

ring were also resonating in the aromatic region at δ 7.18 (6H, m, H-3’, 4’, 5’) and

7.25 (4H, m, H-2’, 6’). The pyrazoline ring protons (H-X, M & A) were centred at

δ 5.23 (2H, dd, JXA=7.1 Hz, JXM=12.1 Hz), 3.76 (2H, dd, JMX=12.1 Hz, JMA=17.2 Hz)

and 3.10 (2H, dd, JAX=7.1 Hz, JAM=17.2 Hz) respectively. A singlet was also found at

δ 4.00 (4H) which may be assigned to OCH2 group hydrogens. UV-Vis spectrum of

231

3.124 showed two maxima at 355 and 252 nm which could be ascribed to n→π* &

π→π* transitions respectively. 13C-NMR (100MHz, DMSO-d6) data of 3.124 had the noticeable signals at δ 158.38,

146.30 & 143.68 which were assignable to C-3, C-4’’’ and C-1’ respectively. The

remaining signals in the aromatic region were found to be placed at δ 132.64 (C-1’’’),

125.80 (C-2’’’, 6’’’), 132.26 (C-2’’, 6’’), 125.74 (C-4’’), 126.16 (C-1’’), 129.18

(C-3’’, 5’’), 125.90 (C-3’, 5’), 117.14 (C-4’), 112.64 (C-2’, 6’) and 113.22

(C-3’’’, 5’’’). Three signals were also observed in the aliphatic region at δ 66.48

(C-5), 63.30 (OCH2) and 43.76 (C-4).

The ESI-MS spectrum of 3.124 exhibited the (M+1) ion at m/z 655 (24%) and its

mass fragmentation pattern was found to be similar as shown in Chart-2

(vide experimental).




The dibenzaldehyde 2.49 was treated with acetophenone under the similar reaction

conditions as described above for 3.116 to yield 3.117 as a brown solid

(77%, m.p. 156-158°C) (Scheme-3.36).

1'

2'

3'

4'

5'6'

1''

2'' 3''

4''

5''6''

O CH2 CH2 CH2 O

OO

12

3

NaOH/EtOH/

O CH2 CH2CH2 O C

O

HC

O

H

2.49

Ph C CH3

O

3.117

Scheme-3.36

IR spectrum of 3.117 had major bands at 2960, 2850 (methylene C-H), 1658 (C=O)

and 1600 (C=C). Its 1H-NMR spectrum (400 MHz, CDCl3) produced a doublet of

doublet at δ 8.00 (4H, dd, Jp,o=1.1, 8.8 Hz) and a multiplet at δ 7.58 (6H, m) which

were easily given by H-2’, 6’ and H-3’, 4’, 5’ respectively. The double bond

hydrogens H-3 & H-2 were resonating at δ 7.78 (2H) & 7.41 (2H) respectively as two

broad doublets and the trans relationship between these hydrogens was confirmed

232

from their coupling value (Jtrans=15.6 Hz). The protons of p-disubsituted benzene

ring H-2’’, 6’’& H-3’’, 5’’ appeared as a triplet of doublet each at δ 7.49

(4H, Jp,o=1.1, 8.8 Hz) and 6.94 (4H, Jp,o=1.1, 8.8 Hz) respectively. Towards the

upfield, two signals present at δ 4.23 (4H, t, Jvic=6.3 Hz) and 2.31 (2H, quintet,

Jvic=6.3 Hz) could be assigned to OCH2CH2 and OCH2CH2 respectively.

The presence of ions at m/z 489 (M+1, 78%), 361 (32%), 348 (100%), 346 (7%), 332

(9%), 325 (55%), 307 (19%), 103 (14%) in the ESI-MS spectrum of 3.117 also

corroborated its structure. Its mass fragmentation pattern has been depicted in

Chart-1 (vide experimental). The UV-Vis spectrum of 3.117 provided two maxima at

353 & 246 nm which may be resulted by n→π* & π→π* transitions respectively.

The carbon framework of 3.117 was confirmed from its 13C-NMR (100 MHz,

DMSO-d6) spectral data. Here recognizable signals were located at δ 190.64 (C=O),

160.90 (C-4’’), 144.66 (C-3) and 119.93 (C-2). The remaining aromatic ring carbon

atoms were found to be resonating at the similar places as described in 3.116. The

aliphatic region was occupied by two resonances at δ 64.44 (OCH2CH2) and 29.12

(OCH2CH2).


The compound 3.117 was refluxed with phenyl hydrazine under the similar conditions

(Scheme-3.37) as used earlier for 3.124 to furnish 3.125 as a brown solid

(75%, m.p. 95-97°C).

1'

2

2'

3

3'

4

4'

5

5'6'

1

1''

2'' 3''4''

5''6''

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

O CH2 CH2CH2 O

OO

12

3


NN HX

HM

HA

O CH2 CH2 CH2 O NNHX

HA

HM

3.117

3.125

Scheme-3.37

IR spectrum of 3.125 did not exhibit any strong absorption at 1658 cm-1 indicating the

absence of C=O group in this compound and the C=N moiety of the pyrazoline ring

generated a band at 1597 cm-1.

233

O CH2

O

CH2 CH2 O

O

m/z 488

m/z 348 (100%)

C CH CH CH2 O

O

CH CH CH O

O

+

CH C C O

O

+

CH C C

O

C

O

CH CHCH H

m/z 361 (32%)

m/z 346 (7%)

m/z 332 (9%)

m/z 307 (19%)

m/z 203 (81%)m/z 103 (14%)

CH CH2 O

O

+

m/z 324 (55%)

m/z 489 (M+1, 78%)

.....

. .. ..

. .. ..

. .. .... .. .

. .. ..

. .. ..

.....

.....

. .. ..

+

+

+

+

+.

.

aa

-C7O2H11

.

.

+.

Chart-1

A comparison of the 1H-NMR spectra (400 MHz, CDCl3) of 3.117 and 3.125 proved

very fruitful to assign the structural feature of later. The signals of H-3 & H-2 in

former at δ 7.78 and 7.41 were found missing altogether in 3.125 which describes

the involvement of enone moiety in the cyclization process. The aromatic protons

H-2’’, 6’’ and H-3’’, 4’’, 5’’ were centred at δ 7.70 (4H, dd, Jp,o=1.1, 8.8 Hz) & 7.38

(6H, m) respectively. Two doublet of doublets present at δ 7.08 (4H, Jp,o=1.1, 8.8 Hz)

and 6.85 (4H, Jp,o=1.1, 8.8 Hz) were assignable to H-2’’’, 6’’’ and H-3’’’, 5’’’

respectively. The resonances centred at δ 7.20 (6H, m) and 7.30 (4H, m) could be

234

easily resulted by H-3’, 4’, 5’ and H-2’, 6’ respectively. The protons H-X, H-M &

H-A belonging to pyrazoline ring furnished three doublets of doublets at δ 5.20


(2H, JAX=7.1 Hz, JAM=17.2 Hz) respectively. A triplet integrating for four hydrogens

at δ 4.08 and a quintet integrating for two hydrogens at δ 2.20 may be represented by

OCH2 and OCH2CH2 group respectively. 13C-NMR (100 MHz, DMSO-d6) data of 3.125 showed the signals of C-3, C-4’’’ and

C-1’ at δ 158.33, 146.31 and 143.70 respectively. Other aromatic carbon atoms were

resonating at the expected δ values. The characteristics pyrazoline ring carbon atoms

C-5 and C-4 were observed in the aliphatic region at δ 66.41 and 43.72 respectively

along with two more signals at δ 63.20 (OCH2) & 25.92 (OCH2CH2).

The ESI-MS spectrum of 3.125 had significant ions m/z 669 (M+1, 6%), 353 (62%),

349 (100%), 237 (98%) and its mass fragmentation pattern has been shown in

Chart-2 (vide experimental).




The compound 3.118 (80%, m.p. 70-72°C) was obtained from the reaction of

dibenzaldeyde 2.50 with acetophenone under the similar reaction conditions as

described above for 3.116 (Scheme-3.38).

1'

2'3'

4'

5'6'

1''

2'' 3''

4''

5''6''

O CH2 (CH2)2 CH2 O

OO

12

3

NaOH/EtOH/

O CH2 (CH2)2 CH2 O C

O

HC

O

H

2.50

Ph C CH3

O

3.118

Scheme-3.38

IR spectrum of 3.118 (Plate-42) revealed important bands at 2931, 2875 (methylene

C-H), 1659 (C=O) and 1598 (C=C). In its 1H-NMR spectrum (400 MHz, CDCl3)

(Plate-43), a doublet of doublet at δ 8.01 (4H, dd, Jp,o=1.1, 8.5 Hz) and a multiplet at

δ 7.57 (6H, m) were easily denoted by H-2’, 6’ & H-3’, 4’, 5’ respectively. The trans

hydrogens H-3 and H-2 of the double bond were centred at δ 7.76 (2H) & 7.41 (2H)

235

respectively as two broad doublets (Jtrans=15.6 Hz). The hydrogens of p-disubsituted

benzene (H-2’’, 6’’& 3’’, 5’’) appeared at δ 7.47 (4H, m) and 6.91 (4H, d, Jo=8.4 Hz)

respectively. The signals of internal chain could be resonating at δ 4.10 (4H, t,

Jvic=5.3 Hz, OCH2CH2) and 2.02 (4H, quintet, Jvic=5.3 Hz, OCH2CH2). UV-Vis

spectrum of 3.118 exhibited two maxima at 347 & 245 nm which may be ascribed to

the n→π* & π→π* transitions respectively.

NN H

H

H

O CH2 CH 2 CH2 O NNH

H

H

NN

O CH C CH2 O NN

+

O CH C CH2 O NN

O C C CH O

N

H

C CH

N

H

C CH

N

H

HC CH CH2 O NNH

H

H

O NNH

H

H

O NNH

H

H

H

C C CH2 O NN

+HC CH O N

NH

NN

H

H

H

H

.

m/z 688

m/z 525 (13%)

-C12H19

-N2

m/z 497 (8%)

-NH2

m/z 481 (23%)

-CO2

m/z 437 (46%)

-C6H5

m/z 360 (50%)

ba

b

m/z 353 (62%)

m/z 313 (8%)

m/z 237 (98%)

-C3H4

-C6H4

m/z 349 (100%)

m/z 261 (34%)

-4H

-C7H4

m/z 298 (4%)

c

m/z 669 (6%, M+1)

+

.....

.....

.....

+

+

+

+

+

+

+

+ .....

a

.....

.

.....a

a

.........

c

+.

Chart-2

236

The ESI-MS spectrum of 3.118 (Plate-45) exhibited the (M+Na+1), (M+Na) and

(M+1) ions at m/z 526 (9%), 525 (18%) and 503 (4%) respectively and its mass

fragmentation pattern was found to be similar as shown in Chart-1

(vide experimental). 13C-NMR (100 MHz, CDCl3) spectrum of 3.118 (Plate-44) had significant signals at

δ 190.60 (C=O), 161.08 (C-4’’), 144.70 (C-3) and 119.82 (C-2). The aromatic carbon

atoms (C-1’, 2’, 3’, 4’, 5’, 6’ & C-1’’, 2’’, 3’’, 5’’, 6’’) were found to resonating at the

expected positions (vide experimental). The OCH2CH2 and OCH2CH2 group of the

intervening chain produced two resonances at δ 67.60 and 25.91 respectively.


The compound 3.118 was refluxed with phenyl hydrazine under the similar conditions

(Scheme-3.39) as used earlier for 3.124 to furnish 3.126 as a light yellow solid

(70%, m.p. 110-112°C).

1'

2

2'

3

3'

4

4'

5

5'6'

1

1''

2'' 3''4''

5''6''

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

O CH2 (CH2)2 CH2 O

OO

12

3


NN HX

HM

HA

O CH2 (CH2)2 CH2 O NNHX

HA

HM

3.118

3.126

Scheme-3.39

The presence of C=N moiety was confirmed by the appearance of a band at 1595 cm-1

in the IR spectrum of 3.126 (Plate-46). Its 1H-NMR spectrum (400 MHz, DMSO-d6)

was found to be similar to that of 3.124 & 3.125. The characteristics pyrazoline ring

protons (H-X, M & A) resulted three well defined doublet of doublets at δ 5.14


(2H, JXA=7.0 Hz, JAM=17.0 Hz) respectively (Plate-47). The phenyl ring hydrogens

belonging to N-1 (H-2’-6’), C-3 (H-2’’-6’’) and C-5 (H-2’’’, 3’’’ & 5’’’, 6’’’) were

resonating at the expected δ and J values in the aromatic region (vide experimental).

The two broad singlets integrating for four hydrogens each at δ 3.73 and 1.81 may be

allotted to internal chain OCH2 and OCH2CH2 group hydrogens respectively. Two

237

maxima exhibited at 368 & 246 nm in the UV-Vis spectrum of 3.126 which may be

ascribed to the n→π* & π→π* transitions respectively.

ESI-MS spectrum of 3.126 (Plate-49) showed significant ions at m/z 706 (M+Na+1,

8%), 705 (M+Na, 12%), 353 (100%), 331 (89%) and its mass fragmentation pattern


In the 13C-NMR (100 MHz, CDCl3) data of 3.126 (Plate-48), the carbon atoms

C-4’’’, C-3 and C-1’ were placed at δ 146.71, 158.49 and 144.90 respectively due to

their bonding to heteroatoms (N & O). The remaining aromatic carbons (C-2’-6’,

C-1’’-6’’, C-1’’’-3’’’ & C-5’’’, 6’’’) were found t o be resonating at the appropriate

δ values (vide experimental). The carbon atoms C-5, OCH2CH2, C-4 and OCH2CH2

were found to be resonating at δ 67.79, 64.03, 43.63 & 29.19 respectively.


The compounds 3.119-3.123 were obtained in good yield from the reactions of

2.51-2.55 with acetophenone under the similar conditions as described earlier for

3.116-3.118. The characterization data of 3.119-3.123 have been given in Table-1.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)n CH2 O

OO

12

3

3.119 (n=3), 3.120 (n=4), 3.121 (n=6), 3.122 (n=8), 3.123 (n=10)


Jtrans=15.8-15.5 Hz

Compd. m.p. (°C)

Yield (%)

IR (υmaxcm-1)

1H-NMR (δ )

13C-NMR (δ ) ESI-MS ( m/z)

C=O C=C H-3* H-2* C=O C-3 C-2

3.119 120-

122

68

1658

1597

7.78 (d)

7.40 (d)

195.17 144.65 117.75 539 (M+Na)+

3.120 80-82

75 1654

1593

7.78 (d)

7.41 (d)

190.37 144.45 115.25 531 (M+1)+

3.121 64-

66

60 1655 1599 7.80 (d)

7.41 (d)

190.17 142.45 115.75 559 (M+1)+

3.122 96-

98

69 1665 1603 7.78 (d)

7.39 (d)

190.13 142.15 112.35 609 (M+Na)+

3.123

86-

88

61 1654 1596 7.75 (d)

7.34 (d)

190.10 142.11 112.32 637 (M+Na)+

238


The compounds 3.127-3.131 were synthesized from the cyclization reactions of


described earlier for 3.124-3.126.

NN OCH2 (CH2)n CH2O N

N

H

H H

H

HHM

A

X

1

2

3 4

5

1'

2'

3'5'

6'

1''

2''

3''

4''

5''

6''1'''

2''' 3'''

4'''

5'''6'''

4'

M

A

X

3.127 (n=3), 3.128 (n=4), 3.129 (n=6), 3.130 (n=8), 3.131 (n=10)

The significant characterization data of 3.127-3.131 have been presented in Table-2.


*JXA= 7.2-7.1 Hz, JXM= 12.3-11.1 Hz, JMA= 17.2-16.2 Hz

Stereochemistry of bispyrazolines 3.124-3.131

NN OCH2 (CH2)n CH2O N

N

H

H H

H

HHM

A

X

1

2

3 4

5

1'

2'

3'5'

6'

1''

2''

3''

4''

5''

6''1'''

2''' 3'''

4'''

5'''6'''

4'

M

A

X

3.124-3.131

n=0, 1, 2, 3, 4, 6, 8, 10

Compd. m.p

(°C)

Yield

(%)

IR

(υmax cm-1)

1H-NMR (δ) 13C-NMR (δ) ESI-MS

(m/z)


3.127 125-127

73 1598 5.22 (dd)

3.80 (dd)

3.11 (dd)

158.33 67.39 41.62 696 (M)+

3.128 160-162

60 1588 5.15 (dd)

3.73 (dd)

3.04 (dd)

158.10 67.41 43.62 733 (M+Na)+

3.129 175-177

67 1596 5.12 (dd)

3.70 (dd)

3.02 (dd)

158.41 67.95 43.65 738 (M)+

3.130 240-242

62 1602 4.88 (dd)

3.70 (dd)

3.30 (dd)

158.18 67.33 43.45 767 (M+1)+

3.131 150-152

60 1603 4.85 (dd)

3.72 (dd)

3.28 (dd)

158.15 67.30 43.42 817 (M+Na)+

239

The stereochemical features of pyrazoline ring in 3.124-3.131 were determined from

the considerations of coupling constants (J). The vicinal coupling constant (3J)

between H-X and H-M was found to be 12.3-11.1 Hz which reflects that these

hydrogens are cis to each other while coupling value of JXA=7.2-7.1 Hz describes the

trans relationships between H-X and H-A. The coupling value of 17.2-16.2 Hz

between non equivalent protons H-M and H-A, evidently explain their geminal

placement at C-4. The phenyl rings placed at N-1 and C-5 are evidently trans oriented

to avoid any intramolecular repulsion.

Antimicrobial evaluations of bischalcones 3.116-3.123 & bispyrazolines

3.124-3.131

The antimicrobial activities of the newly prepared compounds 3.116-3.123 &

3.124-3.131 were screened against five bacterial strains namely Bacillius subtilis

(MTCC 441), Staphylococcus aureus (MTCC 96), Escherichia coli (MTCC 443),

Klubsellia pneumeniae (MTCC 3384), Pseudomonas aeruginosa (MTCC 424) and

three fungi strains Aspergillius janus (MTCC 2751), Aspergillius niger (MTCC 281)

& Pencillium glabrum (MTCC 4951). The in vitro zones of inhibitions (mm) and

minimum inhibitory concentration (µg/ml) of these compounds were determined by

using paper disc method10 and serial tube dilution method11 respectively. There

analysis were performed according to the similar procedures which are described on

page no. 43,44 (Chapter-IIa ). The results of zone of inhibition (mm) and MIC

(µg/ml) determinations of bischalcones 3.116-3.123 & bispyrazolines 3.124-3.131

have been presented in Table-3 (Figure-1 & Figure-3) and Table-4 (Figure-2 &

Figure-4) respectively.

It is clear from Table-3 that the compounds 3.117, 3.118, 3.126, 3.127 & 3.130

exhibited significant zone of inhibition (11-13 mm) against Aspergillius niger and the

compounds 3.120, 3.121, 3.125 & 3.126 were having zone of inhibition of 11-12 mm

against the strain Staphylococcus aureus. The compounds 3.126 & 3.131 inhibited the

growth of Aspergillius janus at the zone of inhibition 11 mm while the compound

3.127 & 3.128 were found to be active against Escherichia coli (zone of inhibition-12

mm) and Pencillium glabrum (zone of inhibition-11 mm). The compounds 3.118 &

3.121 had the zone of inhibition 11 & 13 mm against the strain Klubsellia pneumeniae

and Pseudomonas aeruginosa respectively. The compound 3.131 was found to be

active against Bacillius subtilis at the zone of inhibition of 11 mm.

240

Table-3. In vitro zone of inhibitions (mm) of bischalcones 3.116-3.123 & bispyrazolines 3.124-3.131



coli

Klubsellia

pneumoniae

Pseudomonas

aeruginosa

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

3.116 -- 8 7 -- -- 6 8 8

3.117 -- 6 7 8 -- 10 7 11

3.118 6 11 9 7 6 7 9 13

3.119 7 9 8 7 7 10 8 10

3.120 9 8 8 11 9 8 -- --

3.121 8 9 13 11 7 6 8 9

3.122 6 -- 9 8 -- 9 -- 6

3.123 -- 10 8 8 7 8 6 --

3.124 8 6 -- 9 6 6 8 9

3.125 7 8 8 11 10 9 6 10

3.126 9 7 10 12 8 11 9 11

3.127 12 -- 8 6 9 9 10 12

3.128 -- 9 9 -- 10 10 11 8

3.129 10 7 -- 6 -- 9 9 6

3.130 -- 8 -- 6 -- 9 6 13

3.131 6 10 9 10 11 11 6 9

Amoxicillin 17 18 21 20 18 -- -- --

Fluconazole -- -- -- -- -- 20 22 24

241

Table- 4. In vitro MIC ( µg/ml) of bischalcones 3.116-3.123 & bispyrazolines 3.124-3.131



coli

Klubsellia

pneumoniae

Pseudomonas

aeruginosa

Staphylococcus

aureus

Bacillius

subtilis

Aspergillus

janus

Pencilluim

glabrum

Aspergillus

niger

3.116 16 8 8 16 32 16 8 32

3.117 16 16 16 16 8 8 8 32

3.118 32 16 16 8 8 8 8 16

3.119 16 8 8 8 16 8 16 8

3.120 4 8 8 8 16 8 4 8

3.121 8 8 8 8 16 16 4 16

3.122 8 16 16 16 8 16 8 4

3.123 8 8 8 8 16 16 4 8

3.124 16 16 16 16 16 16 8 16

3.125 16 8 8 32 32 8 16 16

3.126 16 4 16 8 16 16 8 16

3.127 32 32 8 4 32 8 16 32

3.128 16 4 8 8 16 16 8 16

3.129 16 4 16 16 8 8 16 16

3.130 16 8 32 16 16 8 16 32

3.131 32 8 32 8 32 16 16 8

Amoxicillin 2 2 2 2 2 -- -- --

Fluconazole -- -- -- -- -- 1 1 1

242

Figure-1. In vitro zone of inhibitions (mm) of bischalcones 3.116-3.123

Figure-2. In vitro MIC ( µg/ml) of bischalcones 3.116-3.123

243

Figure-3. In vitro zone of inhibitions (mm) for bispyrazolines 3.124-3.131

Figure-4. In vitro MIC (µg/ml) for bispyrazolines 3.124-3.131

Table-4 describes that compound 3.120 inhibited the growth of Escherichia coli at

MIC-4 µg/ml while the compound 3.126, 3.128 & 3.129 showed similar activity against

the strain Klubsellia pneumeniae. The compound 3.127 was found to be equally active

against Staphylococcus aureus while the compound 3.120, 3.121 & 3.123 exhibited the

activity of similar order against Pencillium glabrum. The compound 3.122 also provided

the MIC of 4 µg/ml against the strain Aspergillius niger. The remaining compounds

showed noticeable activity at MIC of 8-32 µg/ml.

244

It is evident from the above zone of inhibition and MIC data that bischalcones linked

through the internal chain of six, eight and twelve carbon atoms furnished noticeable

antifungal properties while the bispyrazolines built around four, six and eight methylene

spacer units provided significant antibacterial behaviour.

It may be concluded that this study describes the general method for the synthesis of

new bispyrazolines linked through the 5-aryl ring under the normal conditions. The

significant antimicrobial activities were provided by the bischalcones and bispyrazolines

linked through the aliphatic chains consisting the even number of methylene groups.

245

Experimental

Synthesis of (2E,2’E)-3,3’-(4,4’-(ethane-1,2-diylbis(oxy))bis(4,1-phenylene)) bis(1-


A mixture of acetophenone (0.910 g, 0.0072 mol), dibenzaldehyde 2.48 (1.0 g,

0.0036 mol) and NaOH (0.01 mol) in EtOH (25.0 ml) was stirred for 12 hrs at room

temperature. The reaction was monitored by TLC. After the completion of reaction,

the resulting mixture was poured into iced-HCl to provide a crude substance which

was crystallized from CH3OH:CHCl3 (1:1) to yield a pure compound 3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

12

3

O CH2

O

CH2 O

O

3.116


250; IR (KBr) cm-1 2964, 2856 (methylene C-H), 1657 (C=O), 1602 (C=C); 1H-NMR

(400 MHz, CDCl3): δ 8.01 (4H, dd, Jp,o=1.1, 8.8 Hz, H-2’, 6’), 7.73 (2H, d,

Jtrans=15.6 Hz, H-3), 7.52 (6H, m, H-3’, 4’, 5’ ), 7.42 (4H, td, Jp,o=1.1, 8.8 Hz, H-2’’,

6’’), 7.39 (2H, d, Jtrans=15.6 Hz, H-2), 6.90 (4H, td, Jp,o=1.1, 8.8 Hz, H-3’’, 5’’), 4.01

(4H, s, OCH2); 13C-NMR (100 MHz, CDCl3): δ 190.22 (C=O), 160.98 (C-4’’), 144.62

(C-3), 138.50 (C-4’), 138.40 (C-1’), 130.22 (C-2’, 6’), 128.50 (C-2’’, 6’’), 128.44

(C-3’, 5’), 127.71 (C-1’’), 119.90 (C-2), 114.95 (C-3’’, 5’’), 64.20 (OCH2); MS(ESI):

m/z 475 (M+1, 100%), 334 (3%), 333 (78%), 332 (23%), 311 (37%), 310 (59%), 304

(38%), 293 (63%), 174 (8%), 74 (9%). Anal. Calc. for C32O4H26: Calc. C, 81.01 %;

H, 5.48 %; Found: C, 81.29 %; H, 5.42 %.

Synthesis of (2E,2’E)-3,3’-(4,4’-(propane-1,3-diylbis(oxy))bis(4,1-phenylene))

bis(1-phenylprop-2-en-1-one) 3.117

The compound 3.117 was synthesized from the reaction of 2.49 (1.0 g, 0.0035 mol)

with acetophenone (0.864 g, 0.0070 mol) under the similar conditions as used earlier

for 3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 CH2 CH2 O

OO

12

3

3.117

246




Jtrans=15.6 Hz, H-3), 7.58 (6H, m, H-3’, 4’, 5’ ), 7.49 (4H, td, Jp,o=1.1, 8.8 Hz, H-2’’,

6’’), 7.41 (2H, d, Jtrans=15.6 Hz, H-2), 6.94 (4H, td, Jp,o=1.1, 8.8 Hz, H-3’’, 5’’), 4.23

(4H, t, Jvic=6.3 Hz, OCH2CH2), 2.31 (2H, quintet, Jvic=6.3 Hz, OCH2CH2); 13C-NMR

(100 MHz, DMSO-d6): δ 190.64 (C=O), 160.90 (C-4’’), 144.66 (C-3), 138.59 (C-4’),

138.48 (C-1’), 130.26 (C-2’, 6’), 128.57 (C-2’’, 6’’), 128.42 (C-3’, 5’), 127.76

(C-1’’), 119.93 (C-2), 114.93 (C-3’’, 5’’), 64.44 (OCH2CH2), 29.12 (OCH2CH2);

MS(ESI): m/z 489 (M+1, 78%), 361 (32%), 348 (100%), 346 (7%), 332 (9%), 325

(55%), 307 (19%), 203 (81%), 103 (14%). Anal. Calc. for C33O4H28: Calc.

C, 81.14 %; H, 5.73 %; Found: C, 81.20%; H, 5.78 %.

Synthesis of (2E,2’E)-3,3’-(4,4’-(butane-1,4-diylbis(oxy))bis(4,1-phenylene))


The compound 3.118 was prepared from the reaction of 2.50 (1.0 g, 0.0034 mol) with

acetophenone (0.816 g, 0.0068 mol) under the similar conditions as used above for

3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)2 CH2 O

OO

12

3

3.118

3.118: White solid; Yield 80%; m.p.: 70-72oC. UV-Vis (MeOH) λmax(nm): 347, 245;

IR (KBr) cm-1 2931, 2875 (methylene C-H), 1659 (C=O), 1598 (C=C); 1H-NMR


Jtrans=15.6 Hz, H-3), 7.57 (6H, m, H-3’, 4’, 5’), 7.47 (4H, m, H-2’’, 6’’), 7.41 (2H, d,

Jtrans=15.6 Hz, H-2), 6.91 (4H, d, Jo=8.4 Hz, H-3’’, 5’’), 4.10 (4H, t, Jvic=5.3 Hz,

OCH2CH2), 2.02 (4H, quintet, Jvic=5.3 Hz, OCH2CH2); 13C-NMR (100 MHz, CDCl3):

δ 190.60 (C=O), 161.08 (C-4’’), 144.70 (C-3), 138.54 (C-1’), 132.57 (C-4’), 130.26

(C-2’, 6’), 128.58 (C-3’, 5’), 128.42 (C-2’’, 6’’), 127.65 (C-1’’), 119.82 (C-2), 114.92

(C-3’’, 5’’), 67.60 (OCH2CH2), 25.91 (OCH2CH2); MS(ESI): m/z 526 (M+Na+1,

9%), 525 (M+Na, 18%), 503 (M+1, 4%), 362 (6%), 361 (39%), 360 (100%), 339

(12%), 338 (47%), 332 (7%), 321 (4%), 202 (38%), 102 (7%). Anal. Calc. for

C34O4H30: Calc. C, 81.20 %; H, 5.97 %; Found: C, 81.14 %; H, 5.92 %.

247

Synthesis of (2E,2’E)-3,3’-(4,4’-(pentane-1,5-diylbis(oxy))bis(4,1-phenylene))


The compound 3.119 was synthesized from the reaction of 2.51 (1.0 g, 0.0032 mol)

with acetophenone (0.778 g, 0.0065 mol) under the similar conditions as used earlier

for 3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)3 CH2 O

OO

12

3

3.119



(400 MHz, CDCl3): δ 8.00 (4H, d, Jo=7.2 Hz, H-2’, 6’), 7.78 (2H, d, Jtrans=15.8 Hz,

H-3), 7.58 (4H, d, Jo=7.6 Hz, H-2’’, 6’’), 7.52 (6H, m, H-3’, 4’, 5’), 7.40 (2H, d,


OCH2CH2CH2), 1.87 (4H, quintet, Jvic=6.3 Hz, OCH2CH2CH2), 1.69 (2H, quintet,

Jvic=6.3 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 195.17 (C=O), 161.27

(C-4’’), 144.65 (C-3), 135.50 (C-1’), 132.53 (C-4’), 129.26 (C-2’, 6’), 128.37 (C-3’,

5’), 128.12 (C-2’’, 6’’), 127.42 (C-1’’), 117.75 (C-2), 115.61 (C-3’’, 5’’), 65.55

(OCH2CH2CH2), 25.70 (OCH2CH2CH2), 23.72 (OCH2CH2CH2); MS(ESI): m/z 539

(M+Na, 70%), 376 (24%), 375 (23%), 374 (31%), 353 (45%), 352 (49%), 346


C, 81.39 %; H, 6.20 %; Found: C, 81.32 %; H, 6.26 %.

Synthesis of (2E,2’E)-3,3’-(4,4’-(hexane-1,6-diylbis(oxy))bis(4,1-phenylene))


The compound 3.120 was obtained from the reaction of 2.52 (1.0 g, 0.0030 mol) with

acetophenone (0.744 g, 0.0062 mol) under the similar conditions as described earlier

for 3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''

4''

5''6''

O CH2 (CH2)4 CH2 O

OO

12

3

3.120

248



(400 MHz, CDCl3): δ 8.01 (4H, d, Jo=7.3 Hz, H-2’, 6’), 7.78 (2H, d, Jtrans=15.7 Hz,

H-3), 7.58 (4H, dd, Jp,o=1.1, 8.8 Hz, H-2’’, 6’’), 7.50 (6H, m, H-3’, 4’, 5’), 7.41

(2H, d, Jtrans=15.7 Hz, H-2), 6.91 (4H, dd, Jp,o=1.1, 8.8 Hz, H-3’’, 5’’), 4.02 (4H, t,

Jvic=6.4 Hz, OCH2CH2CH2), 1.84 (4H, quintet, Jvic=6.4 Hz, OCH2CH2CH2), 1.56

(4H, t, Jvic=6.4 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 190.37 (C=O),

161.25 (C-4’’), 144.45 (C-3), 133.50 (C-1’), 132.33 (C-4’), 128.17 (C-3’, 5’), 128.10

(C-2’, 6’), 126.22 (C-2’’, 6’’), 125.42 (C-1’’), 115.25 (C-2), 115.21 (C-3’’, 5’’), 65.50

(OCH2CH2CH2), 25.70 (OCH2CH2CH2), 21.33 (OCH2CH2CH2); MS(ESI): m/z 554

(M+Na+1, 16%), 553 (M+Na, 40%), 531 (M+1, 4%), 376 (7%), 360 (100%), 358

(112%), 338 (48%), 332 (13%), 321 (8%), 202 (28%), 102 (5%). Anal. Calc. for




The compound 3.121 was prepared from the reaction of 2.53 (1.0 g, 0.0026 mol) with

acetophenone (0.714 g, 0.0058 mol) under the similar conditions as used above for

3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)6 CH2 O

OO

12

3

3.121




Jtrans=15.5 Hz, H-3), 7.60 (6H, m, H-3’, 4’, 5’), 7.50 (4H, m, H-2’’, 6’’), 7.41 (2H, d,


OCH2CH2CH2CH2), 1.81 (4H, quintet, Jvic=6.4 Hz, OCH2CH2CH2CH2), 1.48 (4H, t,

Jvic=5.4 Hz, OCH2CH2CH2CH2), 1.41 (4H, t, Jvic=5.6 Hz, OCH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 190.17 (C=O), 160.25 (C-4’’), 142.45 (C-3), 132.31

(C-4’), 131.50 (C-1’), 128.15 (C-2’, 6’), 127.17 (C-3’, 5’), 126.32 (C-2’’, 6’’), 125.02

(C-1’’), 115.75 (C-2), 114.21 (C-3’’, 5’’), 63.45 (OCH2CH2CH2CH2), 24.33

(OCH2CH2CH2CH2), 23.89 (OCH2CH2CH2CH2), 14.03 (OCH2CH2CH2CH2);

249

MS(ESI): m/z 559 (M+1, 50%), 404 (100%), 388 (32%), 386 (26%), 360 (19%), 349


C, 82.31 %; H, 6.85 %; Found: C, 82.36 %; H, 6.89 %.

Synthesis of (2E,2’E)-3,3’-(4,4’-(decane-1,10-diylbis(oxy))bis(4,1-phenylene))


The compound 3.122 was synthesized by reacting 2.54 (1.0 g, 0.0024 mol) with


for 3.116.

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)8 CH2 O

OO

12

3

3.122




Jtrans=15.5 Hz, H-3), 7.56 (6H, m, H-3’, 4’, 5’), 7.47 (4H, d, Jo=8.9 Hz, H-2’’, 6’’),

7.39 (2H, d, Jtrans=15.5 Hz, H-2), 6.36 (4H, d, Jo=8.8 Hz, H-3’’, 5’’), 3.99 (4H, t,

Jvic=6.9 Hz, OCH2CH2CH2CH2CH2), 1.80 (4H, quintet, Jvic=6.4 Hz,

OCH2CH2CH2CH2CH2), 1.46 (4H, t, Jvic=5.4 Hz, OCH2CH2CH2CH2CH2), 1.40

(4H, t, Jvic=5.6 Hz, OCH2CH2CH2CH2CH2), 1.20 (4H, t, Jvic=6.9 Hz,

OCH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 190.13 (C=O), 157.25

(C-4’’), 142.15 (C-3), 135.50 (C-1’), 132.11 (C-4’), 128.10 (C-2’, 6’), 126.20 (C-3’,

5’), 123.12 (C-2’’, 6’’), 122.32 (C-1’’), 112.35 (C-2), 111.31 (C-3’’,5’’), 65.45



(OCH2CH2CH2CH2CH2); MS(ESI): m/z 609 (M+Na, 32%), 432 (40%), 416 (47%),

414 (63%), 388 (63%), 377 (49%), 376 (54%), 258 (67%), 158 (34%). Anal. Calc. for


Synthesis of (2E,2’E)-3,3’-(4,4’-(dodecane-1,12-diylbis(oxy))bis(4,1-phenylene))


The compound 3.123 was obtained by reacting 2.55 (1.0 g, 0.0022 mol) with


for 3.116.

250

1'

2'3'

4'

5'6'

1''

2'' 3''4''

5''6''

O CH2 (CH2)10 CH2 O

OO

12

3

3.123




Jtrans=15.5 Hz, H-3), 7.54 (6H, m, H-3’, 4’, 5’), 7.42 (4H, d, Jo=8.9 Hz, H-2’’, 6’’),

7.34 (2H, d, Jtrans=15.5 Hz, H-2), 6.32 (4H, d, Jo=8.8 Hz, H-3’’, 5’’), 3.96 (4H, t,

Jvic=6.9 Hz, OCH2CH2CH2CH2CH2CH2), 1.78 (4H, quintet, Jvic=6.4 Hz,

OCH2CH2CH2CH2CH2CH2), 1.48 (4H, t, Jvic=5.4 Hz, OCH2CH2CH2CH2CH2CH2),

1.38 (4H, t, Jvic=5.6 Hz, OCH2CH2CH2CH2CH2CH2), 1.15 (8H, t, Jvic=6.9 Hz,


(C-4’’), 142.11 (C-3), 135.45 (C-1’), 132.10 (C-4’), 128.11 (C-2’, 6’), 126.22 (C-3’,

5’), 123.10 (C-2’’, 6’’), 122.31 (C-1’’), 112.32 (C-2), 111.30 (C-3’’, 5’’), 65.43



(OCH2CH2CH2CH2CH2CH2), 11.21 (OCH2CH2CH2CH2CH2CH2); MS(ESI): m/z 637

(M+Na, 10%), 615 (M+1, 16%), 581 (13%), 536 (27%), 535 (11%), 527 (51%), 515

(6%), 514 (28%), 513 (100%), 400 (3%), 392 (8%), 391 (28%), 388 (5%), 361 (12%),

360 (67%), 339 (13%), 321 (9%), 303 (4%), 274 (12%), 202 (13%), 106 (7%), 104

(15%). Anal. Calc. for C42O4H46: Calc. C, 82.08 %; H, 7.49 %; Found:

C, 82.16 %; H, 7.54 %.

Synthesis of 1,2-bis(4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl) phenoxy)

ethane 3.124

A mixture of bischalcone 3.116 (1.0 g, 0.0020 mol), phenyl hydrazine (0.4426 g,

0.0040 mol) and glacial AcOH (5 ml) in dry EtOH (30 ml) was refluxed for 8 hrs. The

progress of reaction was monitored by TLC. The resulting reaction mixture was

concentrated under vacuum to obtain a solid product which was crystallized from

MeOH to yield pure bispyrazoline 3.124.

251

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA

O CH2 CH2 O NNHX

HA

HM

3.124


IR (KBr) cm-1 2922, 2846 (methylene C-H), 1590 (C=N); 1H-NMR (400 MHz,

CDCl3): δ 7.67 (4H, dd, Jp,o=1.1, 8.8 Hz, H-2’’, 6’’), 7.36 (6H, m, H-3’’, 4’’, 5’’),

7.25 (4H, m, H-2’, 6’), 7.18 (6H, m, H-3’, 4’, 5’), 7.12 (4H, dd, Jp,o=1.1, 8.8 Hz,

H-2’’’, 6’’’), 6.80 (4H, dd, Jp,o=1.1, 8.8 Hz, H-3’’’, 5’’’), 5.23 (2H, dd, JXA=7.1 Hz,

JXM=12.1 Hz, HX), 4.00 (4H, s, OCH2), 3.76 (2H, dd, JMA=17.2 Hz, JMX=12.1 Hz,

HM), 3.10 (2H, dd, JAX=7.1 Hz, JAM=17.2 Hz, HA); 13C-NMR (100 MHz, DMSO-d6):

δ 158.38 (C-3), 146.30 (C-4’’’), 143.68 (C-1’), 132.64 (C-1’’’), 132.26 (C-2’’, 6’’),

129.18 (C-3’’, 5’’), 126.16 (C-1’’), 125.90 (C-3’, 5’), 125.80 (C-2’’’, 6’’’), 125.74

(C-4’’), 117.14 (C-4’), 113.22 (C-3’’’, 5’’’), 112.64 (C-2’, 6’), 66.48 (C-5), 63.30

(OCH2), 43.76 (C-4); MS(ESI): m/z 655 (M+1, 24%), 479 (9%), 435 (16%), 402

(61%), 392 (42%), 391 (100%), 385 (81%), 381 (59%), 354 (34%), 326 (28%). Anal.

Calc. for C44O2N4H38: Calc. C, 80.73 %; H, 5.81 %; N, 8.56 %; Found:

C, 80.91 %; H, 5.88 %; N, 8.49 %.


propane 3.125


with phenyl hydrazine (0.443 g, 0.00400 mol) under similar the conditions as


2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA

O CH2 CH2 CH2 O NNHX

HA

HM

3.125

252


IR (KBr) cm-1 2926, 2849 (methylene C-H), 1597 (C=N); 1H-NMR (400 MHz,

CDCl3): δ 7.70 (4H, dd, Jp,o=1.1, 8.8 Hz, H-2’’, 6’’), 7.38 (6H, m, H-3’’, 4’’, 5’’),

7.30 (4H, m, H-2’, 6’), 7.20 (6H, m, H-3’, 4’, 5’), 7.08 (4H, dd, Jp,o=1.1, 8.8 Hz,

H-2’’’, 6’’’), 6.85 (4H, dd, Jp,o=1.1, 8.8 Hz, H-3’’’, 5’’’), 5.20 (2H, dd, JXA=7.1 Hz,

JXM=12.1 Hz, HX), 4.08 (4H, t, Jvic=6.3 Hz, OCH2CH2), 3.78 (2H, dd, JAM =17.2 Hz,

JMX=12.1 Hz, HM), 3.08 (2H, dd, JAX=7.1 Hz, JAM=17.2 Hz, HA), 2.20 (2H, quintet,

Jvic=6.3 Hz, OCH2CH2); 13C-NMR (100 MHz, CDCl3): δ 158.33 (C-3), 146.31

(C-4’’’), 143.70 (C-1’), 132.61 (C-1’’’), 132.15 (C-2’’, 6’’), 129.26 (C-3’’, 5’’),

126.03 (C-1’’), 125.94 (C-3’, 5’), 125.78 (C-2’’’, 6’’’), 125.71 (C-4’’), 117.01 (C-4’),

112.44 (C-2’, 6’), 113.19 (C-3’’’, 5’’’), 66.41 (C-5), 63.20 (OCH2CH2), 43.72 (C-4),

25.92 (OCH2CH2); MS(ESI): m/z 669 (M+1, 6%), 525 (13%), 497 (8%), 481 (23%),

437 (46%), 360 (50%), 353 (62%), 349 (100%), 313 (8%), 298 (4%), 261 (34%), 237


C, 80.56 %; H, 5.93 %; N, 8.44 %.


butane 3.126


with phenyl hydrazine (0.430 g, 0.00398 mol) under the similar conditions as


2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.126

3.126: Light yellow solid; Yield 70%; m.p.: 110-112oC. UV-Vis (MeOH) λmax(nm):

368, 246; IR (KBr) cm-1 2919, 2870 (methylene C-H), 1595 (C=N); 1H-NMR (400

MHz, CDCl3): δ 7.65 (4H, dd, Jp,o=1.4, 8.5 Hz, H-2’’, 6’’), 7.30 (4H, m, H-3’’, 5’’),

7.22 (2H, m, H-4’’), 7.10 (8H, m, H-2’, 3’, 5’, 6’), 7.01 (4H, dt, Jp,o=1.1, 8.5 Hz,

H-2’’’, 6’’’), 6.74 (4H, dt, Jp,o=1.1, 8.6 Hz, H-3’’’, 5’’’), 6.68 (2H, dt,

Jm,o=2.6, 4.6 Hz, H-4’), 5.14 (2H, dd, JXM =12.2 Hz, JXA=7.0 Hz, HX), 3.90 (4H, brs,

253

OCH2CH2), 3.69 (2H, dd, JXM =12.2 Hz, JMA=17.0 Hz, HM), 3.04 (2H, dd,

JAX =7.0 Hz, JAM=17.0 Hz, HA), 1.85 (4H, brs, OCH2CH2); 13C-NMR (100 MHz,

CDCl3): δ 158.49 (C-3), 146.71 (C-4’’’), 144.90 (C-1’), 134.49 (C-1’’’), 132.84

(C-2’’, 6’’), 128.92 (C-3’’, 5’’), 127.03 (C-1’’), 125.85 (C-2’’’, 6’’’), 125.71 (C-4’’),

125.36 (C-3’, 5’), 119.03 (C-4’), 115.01 (C-2’, 6’), 113.40 (C-3’’’, 5’’’), 67.79 (C-5),

64.03 (OCH2CH2), 43.63 (C-4), 29.19 (OCH2CH2); MS(ESI): m/z 706 (M+Na+1,

8%), 705 (M+Na, 12%), 507 (8%), 463 (12%), 420 (6%), 419 (16%), 413 (22%), 409

(13%), 382 (21%), 381 (83%), 354 (19%), 353 (100%), 331 (89%), 174 (14%). Anal.

Calc. for C46O2N4H42: Calc. C, 80.93 %; H, 6.15 %; N, 8.21 %; Found: C, 80.74 %;

H, 6.10 %; N, 8.15 %.

Synthesis of 1,5-bis(4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl)

phenoxy)pentane 3.127

The compound 3.127 was prepared by reacting 3.119 (1.0 g, 0.00192 mol) with

phenyl hydrazine (0.4186 g, 0.003874 mol) under the similar conditions described

above for 3.124.

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.127

3.127: Yellow solid; Yield 73%; m.p. 125-127oC. UV-Vis (MeOH) λmax(nm): 356,

240; IR (KBr) cm-1 2946, 2830 (methylene C-H), 1598 (C=N); 1H-NMR (400 MHz,

CDCl3): δ 7.72 (4H, d, Jo=7.8 Hz, H-2’’, 6’’), 7.37 (4H, dd, Jp,o=1.1, 8.8 Hz, H-2’’’,

6’’’), 7.30 (6H, m, H-3’’, 4’’, 5’’), 7.20 (6H, m, H-3’, 4’, 5’), 7.11 (4H, m, H-2’, 6’),

6.85 (4H, dd, Jp,o=1.1, 8.8 Hz, H-3’’’, 5’’’), 5.22 (2H, dd, JXA=7.1 Hz, JXM=11.1 Hz,

HX), 3.95 (4H, t, Jvic=6.3 Hz, OCH2CH2CH2), 3.80 (2H, dd, JMX=11.1 Hz,

JMA=16.2 Hz, HM), 3.11 (2H, dd, JAX=7.1 Hz, JAM=16.2 Hz, HA), 1.82 (4H, quintet,

Jvic=6.3 Hz, OCH2CH2CH2), 1.64 (2H, quintet, Jvic=6.3 Hz, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 158.33 (C-3), 146.45 (C-4’’’), 144.60 (C-1’), 134.21

(C-1’’’), 132.02 (C-2’’, 6’’), 127.46 (C-3’’, 5’’), 125.03 (C-1’’), 123.60 (C-2’’’, 6’’’),

123.42 (C-3’, 5’), 120.91 (C-4’’), 119.21 (C-4’), 114.40 (C-2’, 6’), 111.29 (C-3’’’,

254

5’’’), 67.39 (C-5), 64.22 (OCH2CH2CH2), 41.62 (C-4), 25.76 (OCH2CH2CH2), 20.76

(OCH2CH2CH2); MS(ESI): m/z 696 (M, 41%), 553 (22%), 525 (25%), 509 (13%),

465 (100%), 388 (7%), 381 (40%), 377 (89%), 341 (98%), 326 (66%), 289 (50%),

265 (71%). Anal. Calc. for C47O2N4H44: Calc. C, 81.03 %; H, 6.32 %; N, 8.04 %;

Found: C, 81.20 %; H, 6.26 %; N, 8.00 %.

Synthesis of 1,6-bis(4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-

yl)phenoxy)hexane 3.128

The compound 3.128 was prepared from the reaction of 3.120 (1.0 g, 0.00188 mol)

with phenyl hydrazine (0.4074 g, 0.003773 mol) under the same conditions as used

earlier for 3.124.

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.128



CDCl3): δ 7.64 (4H, dd, Jp,o=1.2, 8.6 Hz, H-2’’, 6’’), 7.32 (4H, m, H-3’’, 5’’), 7.20

(2H, m, H-4’’), 7.14 (8H, m, H-2’, 3’, 5’, 6’), 7.00 (4H, dt, Jp,o=1.1, 8.4 Hz, H-2’’’,

6’’’), 6.78 (4H, dt, Jp,o=1.1, 8.4 Hz, H-3’’’, 5’’’), 6.67 (2H, td, Jm,o=2.4, 4.8 Hz,

H-4’), 5.15 (2H, dd, JXA=7.2 Hz, JXM=12.2 Hz, HX), 3.84 (4H, t, Jvic=6.4 Hz,

OCH2CH2CH2), 3.73 (2H, dd, JMX=12.2 Hz, JMA=17.1 Hz, HM), 3.04 (2H, dd,

JAX=7.2 Hz, JAM=17.1 Hz, HA), 1.70 (4H, quintet, Jvic=6.1 Hz, OCH2CH2CH2), 1.45

(4H, m, OCH2CH2CH2); 13C-NMR (100 MHz, CDCl3): 158.10 (C-3), 146.51 (C-4’’’),

144.70 (C-1’), 134.51 (C-1’’’), 130.05 (C-2’’, 6’’), 128.66 (C-3’’, 5’’), 127.03

(C-1’’), 125.91 (C-4’’), 125.70 (C-2’’’, 6’’’), 125.44 (C-3’, 5’), 119.01 (C-4’), 114.44

(C-2’, 6’), 113.39 (C-3’’’, 5’’’), 67.41 (C-5), 64.00 (OCH2CH2CH2), 43.62 (C-4),

29.09 (OCH2CH2CH2), 26.53 (OCH2CH2CH2); MS(ESI): m/z 733 (M+Na, 93%), 535

(90%), 491 (28%), 448 (100%), 447 (89%), 441 (38%), 437 (43%), 410 (59%), 409

(19%), 382 (73%), 381 (7%), 359 (25%). Anal. Calc. for C48O2N4H46: Calc.

C, 81.12 %; H, 6.47 %; N, 7.88 %; Found: C, 81.38 %; H, 6.41 %; N, 7.93 %.

255

Synthesis of 1,8-bis(4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl)phenoxy)octane

3.129


with phenyl hydrazine (0.387 g, 0.003584 mol) under similar conditions as described

above for 3.124.

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.129



CDCl3): δ 7.62 (4H, dd, Jp, o=1.0, 8.7 Hz, H-2’’, 6’’), 7.32 (4H, m, H-3’’, 5’’), 7.20


6’’’), 6.76 (4H, dt, Jp,o=1.0, 8.4 Hz, H-3’’’, 5’’’), 6.68 (2H, td, Jm,o=2.6, 4.8 Hz, H-4’),

5.12 (2H, dd, JXA=7.2 Hz, JXM=12.3 Hz, HX), 3.81 (4H, t, Jvic=6.4 Hz,

OCH2CH2CH2CH2), 3.70 (2H, dd, JMX=12.3 Hz, JMA=17.0 Hz, HM), 3.02 (2H, dd,

JAX=7.2 Hz, JAM=17.0 Hz, HA), 1.66 (4H, quintet, Jvic=6.0 Hz, OCH2CH2CH2CH2),

1.35 (4H, m, OCH2CH2CH2CH2), 1.28 (4H, m, OCH2CH2CH2CH2); 13C-NMR

(100 MHz, CDCl3): δ 158.41 (C-3), 146.74 (C-4’’’), 144.36 (C-1’), 134.46 (C-1’’’),

132.85 (C-2’’, 6’’), 129.97 (C-1’’), 128.85 (C-3’’, 5’’), 125.84 (C-3’, 5’), 125.73

(C-4’’), 125.35 (C-2’’’, 6’’’), 119.04 (C-4’), 114.66 (C-2’, 6’), 113.43 (C-3’’’, 5’’’),

67.95 (C-5), 64.34 (OCH2CH2CH2CH2), 43.65 (C-4), 29.31 (OCH2CH2CH2CH2),

29.26 (OCH2CH2CH2CH2), 26.01 (OCH2CH2CH2CH2); MS(ESI): m/z 738 (M, 45%),

563 (21%), 519 (100%), 486 (33%), 476 (9%), 475 (12%), 469 (63%), 465 (50%),

438 (71%), 410 (84%), 409 (18%). Anal. Calc. for C50O2N4H50: Calc. C, 81.21 %;

H, 6.62 %; N, 7.73 %; Found: C, 81.15 %; H, 6.58 %; N, 7.68 %.


decane 3.130


phenyl hydrazine (0.3686 g, 0.003412 mol) under the similar conditions as given

above for 3.124.

256

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.130





6’’’), 6.75 (4H, dt, Jp,o=1.0, 8.9 Hz, H-3’’’, 5’’’), 6.63 (2H, td, Jm,o=2.6, 4.9 Hz, H-4’),

4.88 (2H, dd, JXA=7.2 Hz, JXM=12.0 Hz, HX), 3.84 (4H, t, Jvic=6.2 Hz,

OCH2CH2CH2CH2CH2), 3.70 (2H, dd, JMX=12.0 Hz, JMA=17.2 Hz, HM), 3.30


OCH2CH2CH2CH2CH2), 1.36 (4H, m, OCH2CH2CH2CH2CH2), 1.24 (4H, m,

OCH2CH2CH2CH2CH2), 1.10 (4H, quintet, Jvic=6.3 Hz, OCH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 158.18 (C-3), 146.30 (C-4’’’), 143.32 (C-1’), 134.24

(C-1’’’), 133.63 (C-2’’, 6’’), 129.63 (C-1’’), 127.96 (C-3’’, 5’’), 125.55 (C-3’, 5’),

125.47 (C-4’’), 125.23 (C-2’’’, 6’’’), 119.01 (C-4’), 114.38 (C-2’, 6’), 113.22 (C-3’’’,

5’’’), 67.81 (OCH2CH2CH2CH2CH2), 67.33 (C-5), 43.45 (C-4), 29.22


(OCH2CH2CH2CH2CH2), 19.11 (OCH2CH2CH2CH2CH2); MS(ESI): m/z 767 (M+1,

51%), 591 (100%), 547 (79%), 504 (44%), 503 (40%), 497 (21%), 493 (84%), 466



Synthesis of 1,12-bis(4-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl)phenoxy)

dodecane 3.131


phenyl hydrazine (0.3482 g, 0.003387 mol) under the similar conditions as described

above for 3.124.

257

2

3 4

5

1

1''

2''3''

4''

5''6''

1'''

2''' 3'''4'''

5'''6'''1'2 '

3'4'

5'

6'

NN HX

HM

HA


HA

HM

3.131





6’’’), 6.72 (4H, dt, Jp,o=1.0, 8.9 Hz, H-3’’’, 5’’’), 6.61 (2H, td, Jm,o=2.6, 4.9 Hz,

H-4’), 4.85 (2H, dd, JXA=7.2 Hz, JXM=12.0 Hz, HX), 3.80 (4H, t, Jvic=6.2 Hz,

OCH2CH2CH2CH2CH2CH2), 3.72 (2H, dd, JMX=12.0 Hz, JMA=17.0 Hz, HM), 3.28



OCH2CH2CH2CH2CH2CH2), 1.12 (8H, quintet, Jvic=6.3 Hz,

OCH2CH2CH2CH2CH2CH2); 13C-NMR (100 MHz, CDCl3): δ 158.15 (C-3), 146.33

(C-4’’’), 143.30 (C-1’), 134.22 (C-1’’’), 133.60 (C-2’’, 6’’), 129.61 (C-1’’), 127.94

(C-3’’, 5’’), 125.50 (C-3’, 5’), 125.42 (C-4’’), 125.20 (C-2’’’, 6’’’), 119.00 (C-4’),

114.34 (C-2’, 6’), 113.20 (C-3’’’, 5’’’), 67.80 (OCH2CH2CH2CH2CH2CH2), 67.30

(C-5), 43.42 (C-4), 29.20 (OCH2CH2CH2CH2CH2CH2), 29.02


(OCH2CH2CH2CH2CH2CH2), 19.10 (OCH2CH2CH2CH2CH2CH2); MS(ESI): m/z 817

(M+Na, 32%), 619 (9%), 575 (14%), 532 (34%), 531 (100%), 525 (21%), 521 (29%),

493 (44%), 465 (17%), 443 (38%). Anal. Calc. for C54O2N4H58: Calc. C, 78.58 %;

H, 6.80 %; N, 7.05 %; Found: C, 78.42 %; H, 6.83 %; N, 7.08 %.

258

References

1. Srinivas, A.; Nagaraj, A. and Reddy, C. H. J. Het. Chem. 2008, 45, 1121.

2. Padmavathi, V.; Reddy, K. V.; Padmaja, A. and Reddy, D. B. Phosphorous, Sulfur

and Silicon 2003, 178, 171.

3. Mazzei, M.; Nieddu, E.; Melloni, E. and Minafra, R. Farmaco II 2003, 58, 121.

4. Modzelewska, A.; Pettit, C.; Achanta, G.; Davidson, N. E.; Huang, P. and Khan, S.

R. Bioorg. Med. Chem. 2006, 14, 3491.

5. Padmavathi, V.; Mohan, A. V. N.; Mahesh, K. and Padmaja, A. Chem. Pharm.

Bull. 2008, 56(6), 815.

6. Ram, V. J.; Saxena, A. S.; Srivastava, S. and Chandra, S. Bioorg. Med. Chem. Lett.

2000, 10, 2159.

7. Srivastava, S.; Joshi, S.; Singh, A. R.; Yadav, S.; Saxena, A. S.; Ram, V. J.;

Chandra, S. and Saxena, J. K. Med. Chem. Res. 2008, 17, 234.

8. Findik, E.; Dingil, A.; Karaman, I. and Ceylan, M. Syn. Commu. 2009, 39, 4362.

9. (a) Gennari, C. Comprehensive Organic Synthesis; Trost, B. M. and Fleming, I.

(Eds.), Pergamon, Oxford, UK, 1991, 2, 629; (b) Mahrwald, R. Modern Aldol

Reactions; Wiley-VCH, Weinheim, Germany, 2004, 1-2; (c) Mukaiyama, T.

Organic Reactions; Dauben W G (Ed.) J. Wiley & Sons: New York, NY, USA,

1982, 28, 203; (d) Healthcock, C. H. Comprehensive Organic Synthesis Trost, B.

M.; Fleming, I. (Eds.), Pergamon, Oxford, UK, 1991, 2, 133.

10. Baurer, A. W.; Kirby, M. M.; Sherris, J. C. and Turck, M. Am. J. Clin. Path. 1966,

45, 493.


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