review article 2-chloroquinoline-3-carbaldehyde ii:...

Hindawi Publishing CorporationJournal of ChemistryVolume 2013 Article ID 851297 13 pageshttpdxdoiorg1011552013851297

Review Article2-Chloroquinoline-3-carbaldehyde IISynthesis Reactions and Applications

Bakr F Abdel-Wahab12 and Rizk E Khidre34

1 Applied Organic Chemistry Department National Research Centre Dokki Giza 12622 Egypt2 Shaqra University Dawadami Saudi Arabia3 Chemical Industries Division National Research Centre Dokki Giza 12622 Egypt4Chemistry Department Faculty of Science Jazan University Saudi Arabia

Correspondence should be addressed to Rizk E Khidre rizkareinyahoocom

Received 13 May 2013 Accepted 17 September 2013

Academic Editor Patricia Valentao

Copyright copy 2013 B F Abdel-Wahab and R E Khidre This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

This review deals with synthesis and reactions of 2-chloroquinoline-3-carbaldehyde during the period from 1979 to 1999 Thereactions are subdivided in groups that cover the reactions of chloro- and aldehyde substituent as well as reactions which involveboth groups Some of these reactions have been applied successfully to synthesis of biologically important compounds The mainpurpose of this review is to present a survey of the literature on 2-chloroquinoline-3-carbaldehyde chemistry and provide usefuland up-to-date data for organic and medicinal chemist since such compound has not been previously reviewed in this period

1 Introduction

Over the past two decades 2-chloroquinoline-3-carbalde-hydes and their derivatives have attracted much attentiondue to their considerable biological and pharmacologicalactivities as antimicrobial [1ndash7] anti-inflammatory [8 9]antimalarial [10] and antivirus activities [11] Despite thisversatile importance and in continuation of our previousreview articles [12ndash16] 2-chloroquinoline-3-carbaldehydeshave not been previously reviewed in the period from 1979 to1999 The present review aims to complete our review articleabout these compounds [14]

2 Synthetic Methods

21 Vilsmeier-Haack Reaction 2-Chloroquinoline-3-carbal-dehydes and 2-chloro-4-methyl-quinoline-3-carbaldehyde 1were prepared from acetanilide [11 17ndash21] and acetoac-etanilide [17] via a Vilsmeier-Haack reaction (Scheme 1)

It was reported that one-pot synthesis of pyrido[23-b]quinolin-2-ones 2 in moderate yields (22ndash59) was ar-chived by treatment of substituted acetanilide with DMF and

POCl3 to produce compound 1 to this reaction mixture a

secondary amide was added in POC13solution containing

one drop of DMF and the mixture was heated for a further2-3 h at 75∘C (Scheme 2) [22]

3 Chemical Reactions

31 Substitution Reactions 3-Formylquinoline-2(1H)-thione(X = S) and -seleno I (X = Se) 3 have been prepared fromreaction of 1 with NaXH (X = S Se) Compounds 3 reactedwith primary amine to produce Schiff rsquos bases 4 (Scheme 3)[23]

Treatment of 2-(3-(13-dioxolan-2-yl)quinolin-2-yl)-N-substituted hydrazinecarbothioamide 7 which is prepared bytwo steps first reaction of 1 with ethylene glycol followedby reaction with hydrazine hydrate to afford 3-(13-dioxolan-2-yl)-2-hydrazinoquinoline 6 The latter compound reactedwith substituted isothiocyanates and with 120572-halocarbonylcompounds which yielded thiazolidinone 8 and thiazo-line derivatives 9 The antimicrobial and inotropic andchronotropic activities of the prepared compounds werestudied (Scheme 4) [3]

2 Journal of Chemistry

N

CHO

ClNH

O

1

R1

R1

R2 R2

(i) POCl3DMF 0∘C

R1 = H COMe R2 = H alkoxy halogen

(ii) Δ 80ndash90 5h

Scheme 1

N ClNH

O

Me

1

N N O

2

CHOR1 R1R1

R2

(i) POCl3DMF 0∘CPOCl3 (75 2-3h)

R2NHAc

Ph R =

R1 = H 3-Me R2 = Ph R1 = 8-Me R2 = 4-MeOC6H4 4-ClC6H4 Et PhCH2


Scheme 2

N

CHO CHO

Cl

NaXH

NH

X NH

X

NR

1

H2NR

3a b 4a bX = S Se R = CH2Ph CHMe2 4-MeC6H4

Scheme 3

RNCS

N Cl

O

O

N NH

O

O

HN NHR

S

N NH

O

O

N

N

S

R Ph

N NH

O

O

N

N

S

R OHO OH1

5

6

8

NH2NH2

EtOCOCH2Br

PhCOCH2Br7 60ndash85

9 35ndash75R = Bz Ph 4-MeC6H4 4-ClC6H4

Scheme 4

Cyclization of compound 1 with CS2in EtOHNaOH

or pyridine gave the triazolo[43-a]quinoline-1-thione 10Treatment of 10 with 60 HCO

2H gave the corresponding

aldehyde 11 [124]Triazolo[43-a] quinolines 15andashc wereprepared and screened as antimicrobial inotropic andchromotropic agents Thus reaction of 2-hydrazino-3-(13-dioxolan-2-yl)quinoline 6with aromatic aldehyde or benzoylchloride followed by fusion in presence of air underwentcyclodehydrogenation to give the target compounds Thelatter compounds were also prepared directly from reactionof compound 1 with aldehyde by fusion (Scheme 5) [24]

Reaction of compound 1 with acetic acid at refluxtemperature leads to formation of quinolone 16 whichwas condensed with ethyl bromoacetate to give ethyl

6-methylfuro[23-b]quinoline-2-carboxylate 17 (Scheme 6)[25]

2H-Pyrano[23-b]quinolin-2-ones 20 were prepared in46ndash95 by treating compound 1with HCl to give quinolones18 which reacted with malonic acid in ethanol in thepresence of pyridine and piperidine followed by cycliza-tion in polyphosphoric acid [26] In a similar manner therelated cyanoacrylic acid and its ethyl ester 21 both gavepyranoquinoline-3-carboxylic acid 22 in 90 yield on treat-ment with PPA (Scheme 7) [18]

Meth-Cohn and coworkers reported replacement of 2-Clgroup of compound 1 by H iodo OH SR (R = alkyl phenyl)CO2H Ph CHO and N

3(giving the tetrazole) as described

in Scheme 8 [18]

Journal of Chemistry 3

RCHO

RCHO

N N

O

O

N

O

O

N NH

O

O

N R

Fusion

Fusion

Fusion

NR

N NN

R

N

O

O

N N

O

O

NPh

N N

O

O

NHS

N NNH

S

6

CHO

CHO

11

10

12

13 14a

H+

H+

H+

CS2NaOH

NHNH2

PhCOClK2CO3

NHNHCOPh

R = Ph 2-HOC6H4 4-MeOC6H4

15andashc14andashc

Scheme 5

N

CHO CHO

Cl

Me Me MeAcOH

NH

O

Br

N O

1 16 17

EtO2CCO2Et

Scheme 6

HCl

NH

CHO

O

NH

O N O O

PPA

PPA

CN

R 2

R

R R

NH

O N O O

R R1

18 19

21 22

R = 7-Me CO2R1

CO2R1 CO2H

CH2(CO2H)2C5H5NpipEtOH

CO2H

R = 6-OMe 7-OMe 7-Cl 8-Me

20 46ndash95

R1 = Et R2 = CN R1 = H R2 = CN

Scheme 7

Compounds 1 reacted with alkylthiol to afford 2-(alkylthiol)quinoline-3-carbaldehydes 31 In an alternatemethod compound 31 was also obtained by the reaction of2-mercaptoquinoline-3-carbaldehyde with ally1 bromideAllyl thioethers 31 were converted into oximes by reac-tion with hydroxylamine hydrochloride in the pres-ence of aqueous sodium bicarbonate Oximes were thenoxidized with aqueous NaOCl to give nitrile oxides

which cyclize spontaneously to dihydro-3H-[12]oxazolo[31015840-4101584045]thiopyrano[23-b] quinolone 34 in 81ndash86 yield Theoxidation was also carried out employing chloramine-T andmercuric acetate (Scheme 9) [27]

Treatment of compound 1with sodium iodide in acetoni-trile followed by reductionwith sodiumborohydride to afford2-iodoquinoline 35 Next Pd(0)-mediated cross-couplingof the latter compound and 2-tributylstannyl acrylic acid


CHO

CHO

CHO CHO

CHO

CHO CHO

CHO

CHO

24

23

28

N Cl

HCl

R

N

CHO

SR

RN I

R

NR

NR

N

R

NaI MeCN

N OH

R

N

R

N NN

N SH

R

1

CO2H

CO2

30 87 29 96

H2O(i) Ethylene glycole(ii) BuLi

(i) Ethylene glycole(ii) BuLi DMF

25 69

NaN3

DMSO

or PhSHt-BuSH

R = t-Bu Ph89

27 80

NaHS

EtOH

26 87ndash95

Scheme 8

N

CHO CHO

CHO

Cl N SH1

RR

N SR

BrSH

N S

N

N S

ON

OH

N SR R R32 33

31

34

aq KOHDMF

NaHCO3 rt

NaOClEt3N

N+Ominus

R = H Me Cl

05 h0∘C

NH2OH middot HCl

Scheme 9

prepared in 95 yield by Pd(0)-promoted hydrostannylationof propiolic acid provided compound 36 in 61 yield Expo-sure of 36 to diphenyl phosphorazidate (DPPA) afforded theacyl azide 37 in an unoptimized 31 isolated yield Cyclo-condensation of azide 37 with 1-(1-cyclohexenyl)pyrrolidineyielded camptothecin 39 via the formation of intermediateenamine 38 (Scheme 10) [20]

32 Addition Reaction on Aldehyde Group Benzimid-azo[210158401101584023][13]thiazino[65-b]quinoline 41 was preparedby the reaction of compound 1 with 2-mercaptobenzim-idazole 40 (Scheme 11) [28]

In the same fashion [124]triazolo[510158401101584023][13]thiazino[65-b]quinolines 43 were synthesized by the reaction ofcompound 1 with 124-triazole-5-thiols 42 (Scheme 12) [29]


N Cl N I N

NPO

N

N NHN O

N N O

1

38

CHO

PhO

PhO

(i) NaI HCl MeCN

(ii) NaBH4 MeOH(iii) DHP TSOH

OTHP

OTHP

OTHP

OTHP

35 96 36 61

37 31

39 30

Bu3Sn

CO2H

CO2H

Pd(PPh3)4CuI DMF

N+ Nminus

CON3Xylene reflux

∙∙

Scheme 10

Cl40 411

N N

HN

HSN S

N

N

OH

CHO

+

Scheme 11

N

1N S

N

N

N

OHNHN

NHS

42 43

CHO

R1

ClR2

R2

+

R1 = H 6- 7- 8-Me 6- 7- 8-OMe 7- 8-Cl R2 = H Me Et

Scheme 12

Reaction between compound 1 and acetone in the pres-ence of piperidine and acetic acid gave 4-(2-chloroquinoline-3-yl)-4-hydroxybutan-2-one 44 accompanied with a smallamount of chalcone Reduction of 120573-keto alcohols 44 withsodium borohydride yielded the diastereoisomer 13-diols45ab in 64ndash92 yield The intramolecular cyclization of13-diols was performed in DMF containing HCl to pro-duce (2R4S) 46a and (2S4S)-24-dimethyl-34-dihydro-2H-pyrano[23-b]quinoline 46b (Scheme 13) [30]

Mg-Al hydrotalcite catalyzes the reaction between com-pound 1 and nitromethane very efficiently to afford threo(1S2R)-1-(2-chloroquinoline-3-yl)-2-nitropropane-1-ol 47a

[6] On the other hand it was reported synthesis of1-(2-chloroquinoline-3-yl)-2-nitroethanol 47b and 2-chloro-3-(2-nitrovinyl)quinoline 48 from reaction of 1 withnitromethane (Scheme 14) [7] The synthesized compoundswere tested in vitro for their antimycotic activity againstAspergillus fumigatus Trichophyton mentagrophytesMicrosporum Gypseum Epidermophyton floccosum andCandida albicans [7]

Grignard reaction of compound 1 with either MeMgIor PhMgI followed by oxidation using pyridiniumchlorochromate gave 3-acetyl-2-chloroquinolines 49 [31]Methyl thieno[23-b]quinoline-2-carboxylates 51 were


N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl

Acetonepiperidine AcOH

Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b

46a 49ndash56 46b 56ndash84

Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2

Mg-Al hydrotalcite (20 ww)THF reflux 6ndash8h

+

47a bthreo (100)

R2 = Me (80) H

R1 = H 7-Me 6-OMe 6-Cl 7-Cl 5-Cl 7-OMe

Scheme 14

prepared in 70ndash80 yield by reaction of ketone 49 withmethyl 2-mercaptoacetate in DMF containing anhydrousK2CO3followed by cyclization in methanol containing

piperidine Compounds 49 were condensed with aromaticaldehyde to give the corresponding chalcones 52 The lattercompounds were cyclocondensed with hydrazine to producepyrazoles 53 (Scheme 15) [32]

Reduction of compound 1 followed by treatmentwith phospours tribromide and salicylaldehyde yieldedchromeno[43-b]quinoline-4-carbaldehyde 54 which wasreduced by Pd-C in methanol to produce 3-(3-(hydroxymethyl)quinolin-2-yl)benzaldehyde 55 (Scheme 16)[33]

Reaction of 4-amino-5-aryl-4H-124-triazole-3-thiols 56with 1 was carried out without solvent using inorganic solidsupports (eg silica or alumina) either in microwave irradi-ation [1 2] or in DMF containing potassium carbonate [5]to give the triazolothiadiazole 57 The synthesized quinoline

derivatives have been assessed for their anti-inflammatoryantibacterial and antifungal activities (Scheme 17) [5]

33 Oxidation of Aldehyde Group Oxidation of compound 1with alkaline silver nitrate in ethanol gave the correspondingacid 53 in 73ndash75 yields 2-Chloroquinoline-3-carboxylicacids 58 reacted with either o-phenylenediamine or 45-dichloro o-phenylenediamine in xylene to afford quino[23-b][15]benzodiazepine-12-ones 54 in 39ndash72 yield In con-trast the reaction of those acids 58 with 45-dimethyl o-phenylenediamine yielded benzimidazoles 60 in 60ndash70yield (Scheme 18) [34]

34 Condensation Reactions

341 Reactions with Active Methylene Compounds Com-pound 1 was condensed with either acetylacetone or ethyl


N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO

R5CHOR5 = C6H5 4-OMeC6H4

R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl

(i) NaBH4 MeOH(ii) PBr3 C6H6

(iii) SalicylaldehydeMeOHPd-C

Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3

R1 = H OMe R2 = Me CH2Ph

Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18

cyanoacetate to give compounds 61 and 62 respectively[35] Methyl thieno[23-b]quinoline-2-carboxylates 63 wereprepared in 70ndash80 yield by cyclocondensation of com-pound 1 with methyl 2-mercaptoacetate in DMF containinganhydrous K

2CO3(Scheme 19) [32]

Chalcones 65 were synthesized from reaction betweencompound 1 and aromatic or heterocycle aldehydes 64

The synthesized chalcones were evaluated for their anti-inflammatory activity (Scheme 20) [8]

Cyclization of chalcones 65 with hydrazine phenyl-hydrazine or thiourea to yield pyrazolylquinolines 61and quinolinylpyrimidine-2-thione 62 respectively wasreported The anti-inflammatory activity of the preparedcompounds was studied (Scheme 21) [9]


N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe

R1 = H OMe R2 R3 = H OMe OEt R4 = H O2N

Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+

R1 = R2 = OMe H R3 = C6H5 4-MeC6H4 4-OMeC6H4 4-FC6H44-F3CC6H4 2 4-diOMeC6H3 3-pyridinyl 2 2-dimethyl-3-furyl

Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N

R1 = R2 = H R3 = Ph 4-OMeC6H4 4-MeC6H4 4-ClC6H4 4-BrC6H4

Scheme 21

Treatment of compound 1 with acetic anhydride andsodium acetate afforded the corresponding 2-oxopyrano[23-b]quinolines 72 Compounds were subjected to ammonia toyield the corresponding naphthyridines 73 The synthesizedcompounds were tested for their antimalarial diuretic clas-togenic and antimicrobial properties (Scheme 22) [10]

Cyclization of chloro(cyanovinyl)quinolines 74 preparedfrom condensation of 1 with 2-(4-chlorophenyl)acetonitrile

with secondary amines (eg piperidine morpholine and 4-methyl-1-piperazine) gave substituted benzonaphthyridines75 in 34ndash98 yield (Scheme 23) [36]

342 Reactions with Hydrazine Hydroxylamine Hydrazides(Thio)Semicarbazide and (Thio)Urea Quinolino[32-f ]-124-triazolo[34-b]124-thiadiazepines 76 were prepared


72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+

75 34ndash98R1 = H 6 7-(MeO)2 R2 = 4-ClC6H4 X = N Y = CH2 X = N Y = O X = N Y = NH

Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2

R1 = H Me MeO R2 = C6H5 4-MeOC6H4 4-ClC6H4 2 4-Cl2C6H3

Scheme 24

by cyclocondensation of 1 with 4-amino-5-aryl-4H-124-triazole-3-thiols 56 in DMF (Scheme 24) [37]

Reaction of compound 1with phenyl hydrazine yielded 1-phenyl-1H-pyrazolo [34-b] quinoline 77 [7 17 38] whereasinteraction with hydroxylamine hydrochloride affordedisoxazole[54-b]quinolines 78 Compounds 1 reacted witho-phenylenediamine and ethylenediamine in a 2 1 molarratio to affordNN1015840-bis-(2-chloroquinoline-3-yl-methylene)-o-phenylenediamines 79a and NN1015840-bis-(2-chloroquinoline-3-yl-methylene)-ethylenediamines 79b respectively Pyrim-ido[45-b]quinolin-2-ol 80a and pyrimido[45-b]quinoline-2-thiol 80b were synthesized from reaction of compound 1with urea and thiourea respectively (Scheme 25) [17]

Preparation of pyrazolo[34-b]quinolines 83 as antiviralagents was reported by treatment of compound 1 withhydroxylamine in EtOH to give oxime 81 Stirring a solutionof 81 and SOCl

2in DMF at 0∘C yielded nitrile 82 which was

refluxed with hydrazine in EtOH to give target compoundswhich showed MIC of 15 120583gmL against herpes simplexvirus type 2 and vasodilator activity with an EC50 of 31Mm(Scheme 26) [11]

Wright and EP reported convenient synthesis of 3-(1H-tetrazol-5-yl)quinolin-2(1H)-one 85 from the reaction of 1with a mixture of formic acid hydroxylamine hydrochlorideand sodium formate at reflux temperature to give 3-cyano-2(1H)-quinolinone 84 followed by treatment of the lattercompound with sodium azide and ammonium chloride[21] On the other hand 4-(1H-tetrazol-5-yl)tetrazolo[15-a]quinoline 86 was synthesized by the same author fromtreating 2-chloroquinoline-3-carbonitrile 82 with sodiumazide and ammonium chloride at reflux temperature(Scheme 27) [39]

2-Chloro-3-cyanoquinoline 82 whichwas prepared fromcompound 1 [40] reacted with hydroxylamine to giveamidoxime 87 which on ring closure in DMF containingpotassium carbonate yielded isoxazoloquinoline 88 in 32yield Reaction of 82 with thiourea furnished 89 which weresubjected to ring closure by reacting with chloroacetonitrilein DMF in the presence of potassium carbonate to yield 90(Scheme 28) [33]

Benzo[b]quinolino[32-f ][14]thiazepines 91a [41] andbenzo[b]quinolino[32-f ][14]oxazepines 91b [42] were syn-thesized from reaction of compound 1with 2-aminothiophe-nol and 2-aminophenol respectively On the other handquinobenzodiazepine 92 dihydroquinobenzodiazepine 93and benzimidazolyl quinoline 94 were prepared from reac-tion of compound 1 with o-phenylenediamine via oxidationintermediate benzimidazole quinolone to benzimidazolylquinoline with simultaneous reduction of quinobenzodi-azepine 92 to dihydroquinobenzodiazepine 93 (Scheme 29)[43]

3-Amino-2H-chromen-2-one 95 reacted with compound1 to give compound 96 Cyclodehydrochlorination of 96 gavebenzopyrano[34-d] benzonaphthyridinones 97 in 50ndash60yield (Scheme 30) [44]

Quinolinecarbaldehyde hydrazones 99 were preparedeither by condensation of compound 1 with substitutedhydrazinecarbothioamides or by addition of hydrazones98 to phenyeleisothiocyanate Cyclocondensation of2-((2-chloroquinoline-3-yl)methylene)-N-arylhydrazinecar-bothioamide 99 with substituted phenacyl bromide gavethiazoles 100 Compounds 99 and 100 were tested againstGram-positive and Gram-negative bacteria (Scheme 31) [4]


78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2

NH2OH middot HClCH3CO2H

PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl

H2NOH middot HCl SOCl2

N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl

HCO2H NH2OH middot HClHCO2Na

NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl

NH2OH middot HCl(i) NH2OH middot HClMeCO2Na

MeOH

(ii) SOCl2 C6H6

(iii) K2CO3 DMFMeCO2Na

NH2

NH2

K2CO3 DMF

K2CO3 DMFClCH2CNThiourea NaOH

Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF

R = H Me Cl OMe X = S O

Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1

R1 R2 = H H H OMe Br H Br OMe Br Br Cl H

Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2

R1 = H 7-Me 8-Me R2 = H MeC6H4 cyclohexyl allyl BuPhCH2 ClC6H4 Ph R3 = Ph 4-MeC6H4 4-BrC6H4

Scheme 31


4 Conclusions

2-Chloroquinoline-3-carbaldehydes are easily available andhave high chemical reactivity due to the presence of twoactive moieties chloro- and aldehyde functions This surveyattempts to summarize the synthetic methods and reactionsof 2-chloroquinoline-3-carbaldehydes from 1979 to 1999

References

[1] S Paul and R Gupta ldquoA simple and fast reaction of 3-substituted-4-amino-5-mercapto-s-triazoles with substitutedaldehydes without solvent under microwave irradiation anenvironment co-friendly synthesisrdquo Indian Journal of ChemicalTechnology vol 5 pp 263ndash266 1998

[2] R Gupta S Paul P Kamotra and A K Gupta ldquoRapidsynthesis of s-triazolo [34-b] [134] thiadiazoles and quinolinesunder microwave irradiationrdquo Indian Journal of HeterocyclicChemistry vol 7 no 2 pp 155ndash156 1997

[3] A M Farghaly N S Habib M A Khalil and O A El-Sayed ldquoSynthesis of novel 2-substituted quinoline derivativesantimicrobial inotropic and chronotropic activitiesrdquoArchiv derPharmazie vol 323 no 4 pp 247ndash251 1990

[4] A M Farghally N S Habib A A B Hazzaa and O A El-Sayed ldquoSynthesis of substituted quinoline-3-carbaldehyde (23-dihydrothiazol-2-ylidene) hydrazones of potential antimicro-bial activityrdquo Journal de Pharmacie de Belgique vol 40 no 6pp 366ndash372 1985

[5] R Gupta A K Gupta S Paul and P L Kachroo ldquoSynthesisand biological activities of some 2-chloro-68-substituted-3-(3-alkylaryl-56-dihydro-s-triazolo[34-b][134]thiadiazol-6-yl)quinolinesrdquo Indian Journal Of Chemistry B vol 37 pp 1211ndash12131998

[6] V J Bulbule V H Deshpande S Velu A Sudalai S Sivasankarand V T Sathe ldquoHeterogeneous henry reaction of aldehydesdiastereoselective synthesis of nitroalcohol derivatives overMg-Al hydrotalcitesrdquo Tetrahedron vol 55 no 30 pp 9325ndash93321999

[7] Z Cziaky F Korodi L Frank and I Czink ldquoSynthesis andantimycotic activity of new 2-chloro-3-(2-nitro)ethyl- and (2-nitro)vlnylquinolinesrdquoHeterocyclic Communications vol 2 no1 pp 63ndash70 1996

[8] F Herencia M L Ferrandiz A Ubeda et al ldquoSynthesis andanti-inflammatory activity of chalcone derivativesrdquo Bioorganicand Medicinal Chemistry Letters vol 8 no 10 pp 1169ndash11741998

[9] O A El-Sayed M El-Semary andM A Khalil ldquoNon-steroidalanti-inflammatory agents synthesis of pyrazolyl pyrazolinyland pyrimidinyl derivatives of quinolonerdquo Alexandria Journalof Pharmaceutical Sciences vol 10 no 1 pp 43ndash46 1996

[10] M Sekar and K J R Prasad ldquoSynthesis of some novel2-oxopyrano[23-b]- and 2-oxopyrido[23-b]quinoline deriva-tives as potential antimalarial diuretic clastogenic and antimi-crobial agentsrdquo Journal of Chemical Technology and Biotechnol-ogy vol 72 pp 50ndash54 1998

[11] M R Bell and J H U S Ackerman US 4920128 1990httpworldwideespacenetcomnumberSearchlocale=en EP

[12] B F Abdel-Wahab R E Khidre and A A Farahat ldquoPyrazole-3(4)-carbaldehyde synthesis reactions and biological activityrdquoArkivoc vol 2011 no 1 pp 196ndash245 2011

[13] W M Abdou and R E Khidre ldquoOverview of the chemicalreactivity of phosphonyl carbanions toward some carbon-nitrogen systemsrdquo Current Organic Chemistry vol 16 no 7 pp913ndash930 2012

[14] B F Abdel-Wahab R E Khidre A A Farahat and A A S El-Ahl ldquo2-Chloroquinoline-3-carbaldehydes synthesis reactionsand applicationsrdquo Arkivoc pp 211ndash276 2012

[15] R E Khidre and B F Abdel-Wahab ldquoApplication of benzoy-laceteonitrile in the synthesis of pyridines derivativesrdquo CurrentOrganic Chemistry vol 17 no 4 pp 430ndash445 2013

[16] R EKhidreHAMohamed andB FAbdel-wahab ldquoSynthesisof 5-membered heterocycles using benzoylacetonitriles as syn-thonrdquo Turkish Journal of Chemistry vol 37 pp 1ndash35 2013

[17] M Kidwai and N Negi ldquoSynthesis of some novel substitutedquinolines as potent analgesic agentsrdquoMonatshefte fur Chemievol 128 no 1 pp 85ndash89 1997

[18] O Meth-Cohn B Narine B Tarnowski et al ldquoA versatile newsynthesis of quinolines and related fused pyridinesmdashpart 9 syn-thetic application of the 2-chloroquinoline-3-carbaldehydesrdquoJournal of the Chemical Society Perkin Transactions 1 vol 9 pp2509ndash2517 1981

[19] O Meth-Cohn B Narine and B Tarnowski ldquoA versatile newsynthesis of quinolines and related fused pyridinesmdashpart 5 thesynthesis of 2-chloroquinoline-3-carbaldehydesrdquo Journal of theChemical Society Perkin Transactions 1 vol 5 pp 1520ndash15301981

[20] J H Rigby and D M Danca ldquoVinyl isocyanates in alkaloidsynthesis Camptothecin model studiesrdquo Tetrahedron Lettersvol 38 no 28 pp 4969ndash4972 1997

[21] Wright and T L EP 120483 1984 httpworldwideespacenetcomnumberSearchlocale=en EP

[22] O Meth-Cohn and B Tarnowski ldquoA versatile new synthesisof quinolines and related fused pyridinesmdashpart IV 1 A simpleone-pot route to pyrido[23-b]quinolin-2-ones from anilidesrdquoTetrahedron Letters vol 21 no 38 pp 3721ndash3722 1980

[23] L E Konstantinovskii R Y Olekhnovitch M S Korobov L ENivorozhkin and V I Minkin ldquoStereodynamical interconver-sion of bis(N-aryl-120572-isopropyl-120573-aminovinylthionato)zinc(II)and -cadmium(II)rdquo Polyhedron vol 10 no 8 pp 771ndash778 1991

[24] M A Khalil N S Habib A M Farghaly and O A El-SayedldquoSynthesis antimicrobial inotropic and chronotropic activitiesof novel 124-triazolo[43-a]quinolinesrdquo Archiv der Pharmazievol 324 no 4 pp 249ndash253 1991

[25] T Tilakraj and S Y J Ambekar ldquoSynthesis and mass spectraof some 2H-pyrano[23-b]quinolin-2-onesrdquo Indian Journal ofChemistry vol 62 pp 251ndash253 1985

[26] R A Pawar P B Bajare and S B Mundade ldquoStudies onVilsmeier-Haack reaction A new route to 2-chloroquinoline-3-carboxyaldehydes an a furoquinoline derivativerdquo Journal of theIndian Chemical Society vol 67 no 8 pp 685ndash686 1990

[27] B Prabhuswamy and S Y Ambekar ldquoSynthetic communica-tions an international journal for rapid communication ofsynthetic organic chemistryrdquo Synthetic Communications vol 29no 20 pp 3477ndash3485 1999

[28] Z Cziaky and F Korodi ldquoA new heterocyclic ring system 13H-Benzimidazo[210158401101584023][13]thiazino[65-b]quinolinerdquoHeterocy-cles vol 36 pp 2475ndash2482 1993

[29] F Korodi Z Cziaky and Z Szabo ldquoFused 124-triazoleheterocycles I Synthesis of novel [124]triazolo[5rsquo1rsquo23][1-3]thiazino[65-b]quinolinesrdquo Heterocycles vol 34 no 9 pp1711ndash1720 1992


[30] Z Cziaky and Z Szabo ldquoSynthesis of 2H-pyrano[23-b]quinolinesmdashpart II preparation and 1H-nmr investigationsof 4-hydroxy-2-methyl-34-dihydro-2H-pyrano[23-b]quino-linesrdquo Journal of Heterocyclic Chemistry vol 32 pp 755ndash7601995

[31] B B Neelima and A P Bhaduri ldquoNovel synthesis ofisoxazolo[54-b]quinolinesrdquo Journal of Heterocyclic Chemistryvol 21 p 1469 1984

[32] B Bhat and A P Bhaduri ldquoA novel one-step synthesis of2-methoxycarbonylthieno[23-b]quinolines and 3-hydroxy-2-methoxycarbonyl-23-dihydrothieno[23-b]-quinolinesrdquo Syn-thesis vol 1984 no 8 pp 673ndash676 1984

[33] R P Srivastava Neelima and A P Bhaduri ldquoSynthetic appli-cations of 2-chloro-3-formylquinolinerdquo Journal of HeterocyclicChemistry vol 24 pp 219ndash222 1987

[34] K R Rao N Bhanumathi and P B Sattur ldquoSynthesis ofnovel quino[23-b][15]benzodiazepin-12-onesrdquo Journal of Het-erocyclic Chemistry vol 28 pp 1339ndash1340 1991

[35] R P Srivastava Neelima and A P Bhaduri ldquoReactions of 2-chloro-3-formylquinolinesrdquo Indian Journal of Chemistry B vol26 pp 418ndash422 1987

[36] R P Srivastava Neelima and A P Bhaduri ldquoA convenient syn-thesis of 23-disubstituted benzo[b][18]naphthyridines a novelannelation reaction of 23-disubstituted quinolinesrdquo Synthesisvol 5 pp 512ndash514 1987

[37] G R Rao and K S Rao ldquoSynthesis and biological activity ofquino[32-f]-124-triazolo[34-b]thiadiazepines a novel tetra-cyclic ring systemrdquo Indian Journal of Pharmaceutical Sciencesvol 53 pp 37ndash39 1991

[38] A M Farghaly N S Habib A A B Hazzaa and O AEl-Sayed ldquoA convenient novel method for the synthesis of1H-pyrazolo[34-b]quinoline and its derivativesrdquo AlexandriaJournal of Pharmaceutical Sciences vol 3 pp 84ndash86 1989


[40] B B Neelima and A P Bhaduri ldquoReactions of 2-chloro-3-formylquinolinesrdquo Indian Journal of Chemistry B vol 23 p 4311984

[41] I Torrini G P Zecchini and M P Paradisi ldquoThe con-densation products of 2-chloro-3-formylquinolines with o-aminothiophenolrdquoHeterocycles vol 27 no 2 pp 401ndash405 1988

[42] G P Zecchini I Torrini and M P Paradisi ldquoSynthesis ofquino23-b 15benzoxazepines a novel tetracyclic ring sys-temrdquo Heterocycles vol 26 no 9 pp 2443ndash2447 1987

[43] N Bhanumathi K R Rao and P B Sattur ldquoNovel forma-tion of 1112-dihydro-6H-quino[23-b] [15] benzodiazepinesreaction of 2-chloroquinoline-3-carbaldehydes with o-phe-nylenediaminerdquoHeterocycles vol 24 no 6 pp 1683ndash1685 1986

[44] K R Prasad and M Darbarwar ldquoSynthesis of [1]ben-zopyrano[34-h]benzo[b]-16-naphthyridine-6-onesrdquo OrganicPreparations and Procedures International vol 27 no 5 pp547ndash550 1995

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


N

CHO

ClNH

O

1

R1

R1

R2 R2

(i) POCl3DMF 0∘C

R1 = H COMe R2 = H alkoxy halogen


Scheme 1

N ClNH

O

Me

1

N N O

2

CHOR1 R1R1

R2

(i) POCl3DMF 0∘CPOCl3 (75 2-3h)

R2NHAc

Ph R =

R1 = H 3-Me R2 = Ph R1 = 8-Me R2 = 4-MeOC6H4 4-ClC6H4 Et PhCH2


Scheme 2

N

CHO CHO

Cl

NaXH

NH

X NH

X

NR

1

H2NR

3a b 4a bX = S Se R = CH2Ph CHMe2 4-MeC6H4

Scheme 3

RNCS

N Cl

O

O

N NH

O

O

HN NHR

S

N NH

O

O

N

N

S

R Ph

N NH

O

O

N

N

S

R OHO OH1

5

6

8

NH2NH2

EtOCOCH2Br

PhCOCH2Br7 60ndash85

9 35ndash75R = Bz Ph 4-MeC6H4 4-ClC6H4

Scheme 4

Cyclization of compound 1 with CS2in EtOHNaOH

or pyridine gave the triazolo[43-a]quinoline-1-thione 10Treatment of 10 with 60 HCO

2H gave the corresponding

aldehyde 11 [124]Triazolo[43-a] quinolines 15andashc wereprepared and screened as antimicrobial inotropic andchromotropic agents Thus reaction of 2-hydrazino-3-(13-dioxolan-2-yl)quinoline 6with aromatic aldehyde or benzoylchloride followed by fusion in presence of air underwentcyclodehydrogenation to give the target compounds Thelatter compounds were also prepared directly from reactionof compound 1 with aldehyde by fusion (Scheme 5) [24]

Reaction of compound 1 with acetic acid at refluxtemperature leads to formation of quinolone 16 whichwas condensed with ethyl bromoacetate to give ethyl

6-methylfuro[23-b]quinoline-2-carboxylate 17 (Scheme 6)[25]

2H-Pyrano[23-b]quinolin-2-ones 20 were prepared in46ndash95 by treating compound 1with HCl to give quinolones18 which reacted with malonic acid in ethanol in thepresence of pyridine and piperidine followed by cycliza-tion in polyphosphoric acid [26] In a similar manner therelated cyanoacrylic acid and its ethyl ester 21 both gavepyranoquinoline-3-carboxylic acid 22 in 90 yield on treat-ment with PPA (Scheme 7) [18]

Meth-Cohn and coworkers reported replacement of 2-Clgroup of compound 1 by H iodo OH SR (R = alkyl phenyl)CO2H Ph CHO and N

3(giving the tetrazole) as described

in Scheme 8 [18]


RCHO

RCHO

N N

O

O

N

O

O

N NH

O

O

N R

Fusion

Fusion

Fusion

NR

N NN

R

N

O

O

N N

O

O

NPh

N N

O

O

NHS

N NNH

S

6

CHO

CHO

11

10

12

13 14a

H+

H+

H+

CS2NaOH

NHNH2

PhCOClK2CO3

NHNHCOPh


15andashc14andashc

Scheme 5

N

CHO CHO

Cl

Me Me MeAcOH

NH

O

Br

N O

1 16 17

EtO2CCO2Et

Scheme 6

HCl

NH

CHO

O

NH

O N O O

PPA

PPA

CN

R 2

R

R R

NH

O N O O

R R1

18 19

21 22

R = 7-Me CO2R1

CO2R1 CO2H


CO2H


20 46ndash95

R1 = Et R2 = CN R1 = H R2 = CN

Scheme 7





CHO

CHO

CHO CHO

CHO

CHO CHO

CHO

CHO

24

23

28

N Cl

HCl

R

N

CHO

SR

RN I

R

NR

NR

N

R

NaI MeCN

N OH

R

N

R

N NN

N SH

R

1

CO2H

CO2

30 87 29 96



25 69

NaN3

DMSO

or PhSHt-BuSH

R = t-Bu Ph89

27 80

NaHS

EtOH

26 87ndash95

Scheme 8

N

CHO CHO

CHO

Cl N SH1

RR

N SR

BrSH

N S

N

N S

ON

OH

N SR R R32 33

31

34

aq KOHDMF

NaHCO3 rt

NaOClEt3N

N+Ominus

R = H Me Cl

05 h0∘C

NH2OH middot HCl

Scheme 9





N Cl N I N

NPO

N

N NHN O

N N O

1

38

CHO

PhO

PhO

(i) NaI HCl MeCN


OTHP

OTHP

OTHP

OTHP

35 96 36 61

37 31

39 30

Bu3Sn

CO2H

CO2H

Pd(PPh3)4CuI DMF

N+ Nminus

CON3Xylene reflux

∙∙

Scheme 10

Cl40 411

N N

HN

HSN S

N

N

OH

CHO

+

Scheme 11

N

1N S

N

N

N

OHNHN

NHS

42 43

CHO

R1

ClR2

R2

+


Scheme 12






N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl


Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b


Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2


+

47a bthreo (100)

R2 = Me (80) H


Scheme 14










N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


RCHO

RCHO

N N

O

O

N

O

O

N NH

O

O

N R

Fusion

Fusion

Fusion

NR

N NN

R

N

O

O

N N

O

O

NPh

N N

O

O

NHS

N NNH

S

6

CHO

CHO

11

10

12

13 14a

H+

H+

H+

CS2NaOH

NHNH2

PhCOClK2CO3

NHNHCOPh


15andashc14andashc

Scheme 5

N

CHO CHO

Cl

Me Me MeAcOH

NH

O

Br

N O

1 16 17

EtO2CCO2Et

Scheme 6

HCl

NH

CHO

O

NH

O N O O

PPA

PPA

CN

R 2

R

R R

NH

O N O O

R R1

18 19

21 22

R = 7-Me CO2R1

CO2R1 CO2H


CO2H


20 46ndash95

R1 = Et R2 = CN R1 = H R2 = CN

Scheme 7





CHO

CHO

CHO CHO

CHO

CHO CHO

CHO

CHO

24

23

28

N Cl

HCl

R

N

CHO

SR

RN I

R

NR

NR

N

R

NaI MeCN

N OH

R

N

R

N NN

N SH

R

1

CO2H

CO2

30 87 29 96



25 69

NaN3

DMSO

or PhSHt-BuSH

R = t-Bu Ph89

27 80

NaHS

EtOH

26 87ndash95

Scheme 8

N

CHO CHO

CHO

Cl N SH1

RR

N SR

BrSH

N S

N

N S

ON

OH

N SR R R32 33

31

34

aq KOHDMF

NaHCO3 rt

NaOClEt3N

N+Ominus

R = H Me Cl

05 h0∘C

NH2OH middot HCl

Scheme 9





N Cl N I N

NPO

N

N NHN O

N N O

1

38

CHO

PhO

PhO

(i) NaI HCl MeCN


OTHP

OTHP

OTHP

OTHP

35 96 36 61

37 31

39 30

Bu3Sn

CO2H

CO2H

Pd(PPh3)4CuI DMF

N+ Nminus

CON3Xylene reflux

∙∙

Scheme 10

Cl40 411

N N

HN

HSN S

N

N

OH

CHO

+

Scheme 11

N

1N S

N

N

N

OHNHN

NHS

42 43

CHO

R1

ClR2

R2

+


Scheme 12






N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl


Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b


Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2


+

47a bthreo (100)

R2 = Me (80) H


Scheme 14










N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


CHO

CHO

CHO CHO

CHO

CHO CHO

CHO

CHO

24

23

28

N Cl

HCl

R

N

CHO

SR

RN I

R

NR

NR

N

R

NaI MeCN

N OH

R

N

R

N NN

N SH

R

1

CO2H

CO2

30 87 29 96



25 69

NaN3

DMSO

or PhSHt-BuSH

R = t-Bu Ph89

27 80

NaHS

EtOH

26 87ndash95

Scheme 8

N

CHO CHO

CHO

Cl N SH1

RR

N SR

BrSH

N S

N

N S

ON

OH

N SR R R32 33

31

34

aq KOHDMF

NaHCO3 rt

NaOClEt3N

N+Ominus

R = H Me Cl

05 h0∘C

NH2OH middot HCl

Scheme 9





N Cl N I N

NPO

N

N NHN O

N N O

1

38

CHO

PhO

PhO

(i) NaI HCl MeCN


OTHP

OTHP

OTHP

OTHP

35 96 36 61

37 31

39 30

Bu3Sn

CO2H

CO2H

Pd(PPh3)4CuI DMF

N+ Nminus

CON3Xylene reflux

∙∙

Scheme 10

Cl40 411

N N

HN

HSN S

N

N

OH

CHO

+

Scheme 11

N

1N S

N

N

N

OHNHN

NHS

42 43

CHO

R1

ClR2

R2

+


Scheme 12






N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl


Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b


Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2


+

47a bthreo (100)

R2 = Me (80) H


Scheme 14










N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N Cl N I N

NPO

N

N NHN O

N N O

1

38

CHO

PhO

PhO

(i) NaI HCl MeCN


OTHP

OTHP

OTHP

OTHP

35 96 36 61

37 31

39 30

Bu3Sn

CO2H

CO2H

Pd(PPh3)4CuI DMF

N+ Nminus

CON3Xylene reflux

∙∙

Scheme 10

Cl40 411

N N

HN

HSN S

N

N

OH

CHO

+

Scheme 11

N

1N S

N

N

N

OHNHN

NHS

42 43

CHO

R1

ClR2

R2

+


Scheme 12






N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl


Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b


Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2


+

47a bthreo (100)

R2 = Me (80) H


Scheme 14










N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N1

N Cl

R R

OH O

NR

OH OH

N Cl

R

OH OH

N

RN

R

OO

CHO

Cl


Cl

NaBH4MeOH

DMFHCl DMFHCl

44 43ndash70

45a 45b


Scheme 13

N

OH

N

1

48

R RR2

R2

Cl Cl

NO2

NO2

NO2


+

47a bthreo (100)

R2 = Me (80) H


Scheme 14










N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

(i) RMgI

(ii)N

R

O

N S

R

O

e

N S

CrO

O

R

N

O

N

N NH

149 50

51

5253

CHO

R2

R2

R3

R3

R4

R4

R1

R2

R3

R4

R1

R1

R2

R3

R4

R1R2

R3

R4

R1

R5

R5

R2

R3

R4

R1

Cl

ClCl

Cl

ClNH+

NH2NH2 middot H2O

PipridineMeOH

CO2Me

CO2Me

SH

K2CO3DMFCO2M

R = Me Ph

R1 = R4 = H R2 R3 = H MeO

minusO


R =Me

Scheme 15

N N

O

N

OH

1 54 55

CHO

CHO CHOCl



Scheme 16

1

N

NN

NN

NH

NS

NN

56 57

CHO

ClCl

R1 R1

R2

R2

+

NH2

SHMW

orDMFK2CO3


Scheme 17

N1

N N NH

NHO

Me Me

Me

Me

N Cl

N

HN

59

60

R1 R1

R1

R1

R2

R2

R2

R2

CHO

Cl Cl

AgNO3EtOHCO2H

H2N

H2N

H2N

H2N

58 73ndash75

R2 = H Clxylene

R1 = H Me OMe

Scheme 18







N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

SH

N S

CN

CNN

1

63

Me Me

OO

N

61

62

R1

R2

R3

R4

R3

R3

R2R2

R1R1

R1

R2

R3

R3

R4R4

CHO

Cl Cl

Cl

CO2Me

EtO2C

CO2MeK2CO3DMF

CO2Et

COMe

COMe

R1 = R3 = R4 = H R2 = H Me OMe


Scheme 19

N N

NaOHEtOHMe

OO

1 64

CHO

Cl Cl

R1

R2

R3

R1

R2

R3

65 56ndash85

+


Scheme 20

N

O N

N

N

NHN

S

S65

66

67

Cl

Cl

Cl

R1

R2

R1

R2

R1

R2

R3

R3

R3

H2N NH2

R4 = H PhR4NHNH2

R4N


Scheme 21






72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


72 73N N O O N N

HO

R R R

1

CHO

Cl

Ac2OAcONa NH3

Scheme 22

N NCN

CNHX Y

N N XY1 74

CHO

Cl Cl

R1 R1R1

R2

R2 R2

+


Scheme 23

1 NN

N

N

S

N

N

NN

N SH DMF

5676

CHO

Cl

R1 R1

R2

R2+

NH2


Scheme 24












78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


78 77

N

R

N N

R

N

PhN

O

R

N

X

N

R

N

N

XH

Y

N

R

Y

N

R

CHO

Cl

Cl

Cl

R1

R1

R1

R1R1

R1

79a b

H2N NH2

H2N NH2

Y = C6H4 CH2CH2


PhNHNH2

CH3CO2H

CH3CO2H

1 R = H Me

80a bX = O SR1 = H 7-Me 8-Me

Scheme 25

N N N

CN

EtOH

EtOH

NOH

DMF

N NH

N

MeO

MeO

MeO MeO

1 81

83

CHO

Cl Cl82

Cl


N2H4 middot H2O

NH2

Scheme 26

1 84

82 86

85

N NH

CN

CN

O NH O

NN

NHN

HN

N N

NN

N

N NN

CHO

Cl

Cl


NaN3 NH4Cl

NaN3 NH4Cl

POCl3

Scheme 27


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


82 87 88

9089

CN

CN

CN

N

NH S N

HS

O

N

NOH

N ON1

Cl Cl


MeOH

(ii) SOCl2 C6H6


NH2

NH2

K2CO3 DMF


Scheme 28

N

R

HX N

R

X

N

N

R

NH

N

N

R

NH N

R NH

N

1 91

92 93 94

CHO

Cl

Cl

+

++

H2N

X = NH

NH

R = H Me OMe

K2CO3DMF


Scheme 29

9695 97

O O

N

O O

N

N

O O

N

Cl

R2

R2R2

R1

R1R1

NH2

+1


Scheme 30

1

98

99 100N

NHN

S

N Cl

N

OBr

N

N N

S

N

ClCl

R1

R1

R2

R3R3

R1

NH2NH2

NH2

R2NHCSNHNH2

PhNCS

NHR2


Scheme 31


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


4 Conclusions


References























































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


























Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

review article 2-chloroquinoline-3-carbaldehyde ii:...

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