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CondensationReactionofVariousNucleophileswithImportantDerivativesof3-Formylchromones

ARTICLE·JANUARY2009

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4AUTHORS,INCLUDING:

SharadShelke

SSGMCollege,Kopargaon,Dist:Ahmednagar

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NileshGovindraoSalunkhe

SantGadgeBabaAmravatiUniversity

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International Journal of Pure & Applied Chemistry 4(1-2), (January-June 2009) pp. 41-45

Condensation Reaction of Various Nucleophiles withImportant Derivatives of 3-Formylchromones

Sharad N. Shelke!", Kisan M. Kodam/, Nilesh G. Salunkhe' &Bhausaheb K. Karale1

IP.G. & Research, Department of Chemistry, S. S. G. M. College, KopargaonDist-Ahmednagar- 423 601, India

2Department of Chemistry, University of Pune, Pune-4II 007, India

l!t

ABSTRACT: Various substituted 3-formylchromones were treated with acid hydrazide A to form correspondinghydrazones 3. Corresponding salicylol pyrazoles 5 were synthesized from hydrazones 3 by treating with potassiumhydroxide. Pyrimidine 6 synthesized from 4-«substituted-4-oxo-4H-chromon-3-yl)methylene)-3-methyl-l-phenyl-IH-pyrazol-5(4H)-ones 2 were synthesed by treating with guanidine in presence of alcoholic potassium hydroxide.3-(2-Hydroxyphenyl)-lH-pyrazole-4-carboxaldehyde 4-carboxaldehydes-7 were obtained from 3-methyl-4-[(chromon-3-yl)-methylene]-1-phenyl pyrazolin-5-(4H)-ones 2 by treating with hydrazine hydrate.

Keywords: 3-Formylchromone, Salicyloyl pyrazoles, Guanidine, Pyrazole

Introduction

Amongst different functionalize chromones, 3-formylchromone occupies unique position because it canconverted into different biologically importantheterocycles. 3-Formylchromone when treated withphenylhydrazine gives 4-salicylol pyrazole [1,2], whereas on treatment with guanidine it gives 5-salicylolpyrimidine in KOH [3].

I

1

The condensation reactions of 3-formylchromoneswith compounds containing active methylene groups arewell known in the literature [4-8]. 3-Formylchromoneand it's derivatives can be converted into differentheterocycles [9].

Formyl group in 3-formylchromone can be protectedby different reagent and such protected derivatives areassociated with important biological activities [10]. So,the protected derivatives of 3-formylchromone giveimportant products by interesting mechanistic pathway[9, 11, 12].

Considering the importance and activities associatedwith the compounds obtained from 3-formylchromone,

To whom correspondence be made:snshelke@yahoo.co.in

interesting ring opening reactions of 3-formylchromone I

and in continuation of our work on 3-formylchromone[13-15] and it's derivatives, it was thought worth whileto carry out condensation of hydrazine and guanidine with3-formylchromone.

In the present study, various substituted3-formylchromones were treated with acid hydrazideA to form corresponding hydrazones 3. Thecorresponding salicyloyl pyrazo\es were formed byheating these hydrazones 3 with potassium hydroxide.Then, pyrimidine 6 were formed by treating4-«substituted-4-oxo-4H-chromon-3-yl)methylene)-3-methyl-l-phenyl-lH-pyrazol-5(4H)-ones 2 withwith guanidine in presence of alcoholic potassiumhydroxide.

ExperimentalAll the recorded melting points were determined in opencapillary tubes and are uncorrected. IR spectra wererecorded on Perkin-Elrner FTIR spectrophotometer inKBr disc. IH NMR spectra were recorded on Varian300 MHz spectrophotometer in DMSO as a solvent andTMS as an internal standard. Peak values are shown ino ppm.

42 Sharad N. SlzeLke. Kisan M. Kodatn, Nilesh C. Salunkhe & Bhausalzeb K. KaraLe

2-( Benzo] d lthiazol-Z: ylthio )-N' -( (substituted-4-oxo-4H-chromon-l-yiimethylene] acetohydrazides 3

A mixture of 3-formyJchromone (0.01 mole) and acidhydrazide A (0.01 mole) in ethanol (50 mL) were refluxedfor 30 min. Solid thus separated was filtered. dried andcrystallized from DMF. Compounds prepared by abovemethod are listed in Table-I with their physical data.

I.R. in cm' I (3a): 3191. 3052, 1694, 1635,1604, 1566,1558,749.

IH NMR (DMSO-d6• 300 MHz) s (3a): 4.17 (s, 2H, -CH2), 7.02 to 8.62 (m, 8R, aromatic and =C-H), 9.72 (s,IH, -NH), 10.2 (s, ut. Chromone C2-H).

MS m/z (3a): 429 (M+), 431(M+2).

(S ubs ti tu ted- 2 -Iiydro xy phenyl)( J H -py razol-A -yl)methanones 5

I 2-(Benzo[dlthiazol-2-ylthio)-N' -«substituted-4-oxo-4H-chromon-3-yl)methylene) acetohydrazide 3 (0.001 mole)and KOH (0.0075 mole) were taken in round bottom flaskwith 10 mL of ethanol as solvent. Reaction mixture washeated under reflux for 3 hr. The contents were cooledto room temperature and poured into crushed ice withvigorous stirring followed by neutralization with aceticacid. Solid product thus obtained was separated byfiltration and crystallized from ethanol to get (Substituted-2-hydroxyphenyl)( IH-pyrazol-4-yl)methanones 5.

Compounds Sa-g was synthesized similarly. The physicaldata of Sa-g are given in Table 1.

IR (KBr) v (Se): 3468, 3143,1632,1571 crrr '.

IH NMR (DMSO-d6• 300 MHz) ii (Se): 2.40 (s, 3H, Ar-CH3), 7.00 to 8.10 (m, 6H, -NH and aromatic protons),11.80 (s, IH, -OH),

MS m/z (Se): 202 (M+).

(Substituted-2-hydroxyphenyl)( J, 2-dihydro-2-iminopyrini idin-S: yl nnethanones 6

A mixture of substituted 4-«substituted-4-oxo-4H-chromon-3-y l)methylene)-3-methyl-l-phenyl-l H-pyrazol-5(4H)-ones 2 (0.005 mole), guanidine (0.008mole) and potassium hydroxide (0.0075 mole) were takenin round bottom flask with 10 mL of ethanol as solvent.Reaction mixture was heated under reflux for 3 hr. Thecontents were cooled to room temperature and pouredinto crushed ice with vigorous stirring followed byneutralization with acetic acid. Solid product thusobtained was separated by filtration and crystallized fromacetic acid to get (Substituted-2-hydroxyphenyl)(l,2-dihydro-2-iminopyrimidin-5-yl)methanones 6.

Compounds 6a-f was synthesized similarly. The physicaldata of 6a-f are given in Table 1.

IR (KBr) v (6a): 3432,3317,3153, 1678,742 crrr '.

IH NMR (DMSO-d6• 300 MHz) a (6a): 6.95 to 7.85 (m,5H, aromatic proton), 8.95 (s, IH, -NH), 9.02 (s, lH, -NH), 11.10 (s, IH, -OH)

MS m/z (6a): 249 (M+), 251 (M+2).

Substituted- J, 4-dihydrochrolllono{ 4, 3-c [pyrazol-a-ols 7

4-«Substituted-4-oxo-4H-chromon-3-yl)methylene)-3-methyl-J-phenyl-I H-pyrazol-5( 4H)-ones 2 (0.001 mole)or schiffs base derived from 3-formylchromone (0.001mole) hydrazine hydrate (3 ml.), potassium hydroxide(0.0075 mole) were taken in round bottom flask with 25mL of ethanol as solvent. Reaction mixture was heatedunder reflux for 5 hr. The contents were cooled to roomtemperature and poured into crushed ice with vigorousstirring followed by neutralization with acetic acid. Solidproduct thus obtained was separated by filtration andcrystallized from acetic acid to get light yellow productSubstituted-I ,4-dihydrochromono[4,3-c]pyrazol-4-0Is 7.

Table 1Characterization Data for Synthesized Compound 3, 5, 6 and 7

Compound RJ R2 s, Melting Yield,Point, "C %

3a H H Cl 221 613b H CH) Cl 218 623e H H CH) 190 613d H CH, H 224 623e H H F 160 603f H H Br 215 573g CH) H CH) 230 635a H H Cl 144 455b H CH) Cl 139 435e H H CH, 120 555d H CH) H 120 505e H H F 131 425f H H Br 147 495g CH) H CH, 142 536a H H Cl 302 486b H CH) Cl 328 506e H H CH, 310 426d H Cl Cl 315 416e Cl H Cl 312 437a H H Cl 282 467b H CH, Cl 284 507e H H CH) 269 497d H CH, H 279 417e Cl H H 278 487f CH, H CH, 283 427g CH, H H 254 40

Condensation Reaction of Various Nucleophiles with Important Derivatives of 3-Formylchrolllones 43

R1

R2l('::r°fi + RSCH2CONHNH,R3~CHO

lOA

Ethanoll heat

R1

R2yY0) Ale. KOH / heatR3~CH=NNHCOCH2SR •.

o

Compounds 7a-g was synthesized similarly. The physicaldata of 7a-g are given in Table 1.

IR (KBr) v (7b): 3400, 3207, 1631,737 crn'.

IH NMR (DMSO-d6, 300 MHz) 8 (7b): 2.35 (s, 3H, Ar-CH3), 6.92 to 7.67 (m, 3H, aromatic and methine proton),8.15 (s, IH, -NH), 8.74 (s, IH, Pyrazole H), 9.9 (s, IH,-OH).

MS m/z (7b): 236 (M+), 219(100 %),198,170,155,128,115,77.

IR (KBr) v (7d): 3209 (bs, -OH and -NH), 1639 (C=N)crn',

IH NMR (DMSO-d6, 300 MHz) 8 (7d): 2.34 (s, 3H,

Ar-CH3), 6.76 to 7.55 (m, 4H, aromatic and methineproton), 8.14 (s, IH, -NH), 8.76 (s, IH, Pyrazole H), 10.09(s, IH, -OH).

MS m/z (7d): 202 (M+), 185(100 %), 170, 155, 145, 128,115,91,77.

Result and Discussion

The starting compound namely 3-formylchromones(variously substituted) are treated with acid hydrazide A

ito form corresponding hydrazones 3. These hydrazones3 are heated with potassium hydroxide to formcorresponding salicyloyl pyrazoles [16] S and not ananticipated product is depicted in Figure 1.

The formation of compounds 3 and S has beenconfirmed by IR, IH NMR and mass spectra. For instance,IR of 3a showed chromone carbonyl stretching at 1694cm', -NH at 3191 cm' and (C=C) at 1566 cm'. The IH

RSH

H2. Eth chloroacetate3. Hydr zine hydrate

NMR of this compound in DMSO-d6 showed a singletat 8 4.17, for methylene group, two singlets wereobserved at d 9.72 (-NH) at 8 10.2 (chromone Cz-H).The aromatic protons showed expected chemical shiftsand splitting pattern. The mass spectra of 3a showed M+and M+2 at 429 and 431 mlz due to presence of chlorine.The band at 1632 cm:' and 3468 cm' in IR spectra of Seshows presence of (C=O) and -OH respectively.

In IH NMR spectra of Se, the singlet at 8 2.40 wasobserved for methyl group. The broad singlet for -NH and-OH appeared down field at 88.10 and 811.80. The massspectra of Se showed M+ at 202. When 4-«substituted-4-oxo-4H-chromon-3-yl)methylene)-3-methyl-l-phenyl-l H-pyrazol-5(4H)-ones 2 treated with guanidine in presenceof alcoholic potassium hydroxide gives pyrimidine 6 andnot a anticipated product. 4-«substituted-4-oxo-4H-chromon-3-yl)methylene )-3-methyl-l-phenyl-l H-pyrazol-5(4H)-ones 2 are synthesized from 3-formylchromone byrepotted method [13] (Figure 2).

The structure of the synthesized compounds 6 has beenproven by IR, IH NMR and Mass spectra. IR of 6a showedcarbonyl stretching at 1678 cm', -OH and -NH at 3432crn' and 3317 cm' respectively. The IH NMR of thiscompound in DMSO-d6 showed singlets for two -NH andone -OH at (5 8.95, (5 9.02 and (5 11.10 respectively. Themass spectra of 6a showed M+ and M+2 at 249 and 251mlz due to presence of chlorine. When 4-«substituted-4-oxo-4H-chromon-3-yl) methylene)-3-methyl-l-phenyl-IH-pyrazol-5(4H)-ones 2 treated with hydrazine hydrategave 3-(2-hydroxypheny 1)-1H- pyrazole-4-carboxaldehyde7 and not a anticipated product (Figure 3).

Q:NWhere R= I )--

~ S

R1

R2n;cOH NI ~ :. 'N-CO-CHrRR3

oAnticipated

3

Figure 1: Synthesis of salicylol pyrazoles 5a-g

44 Sharad N. Shelke, Kisan M. Kodam, Nilesh G. SaLunkhe & Bhausaheb K. Karale

NHAnticipated

Figure 2: Synthesis of Pyrimidines 6a-e

RI

R'~O- I I +R

3"'-:::; CHO

o

1

-----l •._R'~OH rHO__ -l1•.~R'~OyOH

Hydrolysis R3~ R3~HN-N HN'N

Hydr tySiSRI ~J

RI ~R2~O R2 I '<:::: OH CH=N-Ar

I I EtOH...-:::; --:OH~y'::::'d';"';ra:""z~i-l1rie~R Q ~R3 CH=N-Ar h d 3 ;,

o y rate HN-N

Anticipated

Anticipated 7

4

Figure 3: Synthesis of Fused Pyrazoles 7a-g

Condensation Reaction of Various Nucleophiles with Important Derivatives of 3-Fonnylchromones 45

The structure of synthesized compounds 7 has beenconfirmed by spectral analysis. For instance, IR of 7drevealed -OH and -NH broad bands at 3209 cm:', (C=N)at 1639 cm:'. The IH NMR of this compound in DMSO-d6 showed a singlet at 0 2.34. for methyl group. Inaddition to the aromatic and methine protons (0 6.76 too 7.55), two broad characteristic signals at 0 8.14 ando 10.09 assignable to -NH and -OH respectively. Themass spectra of 7d showed M+ at 202 mh.

Acknowledgement

Authors are thankful to the Principal G. T. Sangle, S. S.G. M. College, Kopargaon, Dist-Ahmednagar forproviding necessary facilities and constantencouragement.

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[21

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