Microwave Assisted Synthesis and Antimicrobial Activities ...Microwave Assisted Synthesis and Antimicrobial Activities of Some 2-Amino-4-aryl-3-cyano-6-(4’-hydroxy phenyl)-pyridines

ISSN: 0973-4945; CODEN ECJHAO

E-Journal of Chemistry

http://www.e-journals.net 2011, 8(1), 119-122

Microwave Assisted Synthesis and

Antimicrobial Activities of Some 2-Amino-4-aryl-3-

cyano-6-(4’-hydroxy phenyl)-pyridines

PRIYA GOTHWAL, GUNWANTI MALHOTRA and Y.K. SRIVASTAVA*

Department of Chemistry

M.P. Govt. P.G. College, Chittorgarh-312001, India

[email protected]

Received 18 May 2010; Accepted 23 July 2010

Abstract: 4’-Hydroxy chalcones were treated with malononitrile in the

presence of ammonium acetate under solventless microwave assisted condition

to get 2-amino-4-aryl-3-cyano-6-(4’-hydroxy phenyl)-pyridines. The prepared

compounds were screened for their antimicrobial activity; some of them have

exhibited promising antimicrobial activity.

Keywords: Pyridine, Chalcone, Microwave assisted synthesis, Solventless.

Introduction

The usage of microwave energy to accelerate the organic reactions is of increasing interest

and offers several advantages over conventional heating techniques1. Synthesis under MWI

can be achieved conveniently and rapidly under solventless conditions which holds a

strategic position, as the solvents are often toxic, expensive, problematic to use and

hazardous to environment. The reactions under microwave irradiation solventless condition

are eco-friendly and are a part of green chemistry2-6

. Literature survey reveals that phenyl

substituted pyridines have been widely investigated due to their pharmaceutical usages.

Among a wide variety of heterocycles that have been explored for developing

pharmaceutically important molecules, cyanopyridines have played a crucial role in

medicinal chemistry. Cyano pyridines were to possess a broad spectrum of biological

activities such as antiviral7, CNS depressent

8 and bactericidal

9 etc.

.

120 Y.K. SRIVASTAVA et al.

Literature survey reveals that among various chalcones, 4’-hydroxy chalcones

have received little attention. Therefore, it was thought worthwhile to synthesize some

new pyridine derivatives using this synthon, under non-conventional microwave

assisted solventless condition. 4’-Hydroxy chalcones (1a-g) were treated with

malononitrile in presence of ammonium acetate to get 2-amino-4-aryl-3-cyano-6-(4’-

hydroxy phenyl)-pyridines (2a-g) (Scheme 1). The reaction was carried out under

MWI solventless condition. For the sake of comparison same reaction was also carried

out by conventional heating method under liquid phase in presence of ethanol as

solvent. The products obtained by both MWI and conventional heating method were

found to be identical. Under conventional heating the reaction time was 6-10 h with

70-72% yield, whereas under MWI conditions the reaction time was brought down up

to 3-5 minutes with improved yield (85-88%), indicating the superiority of microwave

assisted method over conventional heating. Furthermore the reaction under solventless

condition is eco-friendly and thus avoiding solvent the whole process becomes

economically viable.

Experimental

All the melting points reported are uncorrected and were taken in open capillaries. The

IR spectra were recorded on Shimadzu IR spectrometer using KBr (υ cm-1

). The PMR

spectra were taken on Bruker DRx-600 spectrometer using TMS as internal standard and

CDCl3 as solvent; (chemical shifts in δ ppm); mass spectra (FAB) were recorded on Jeol

Sx-600 mass spectrometer using m-nitro benzyl alcohol as matrix. The matrix peaks

were observed at m/z 307, 289, 154, 137 and 136 respectively. All the transformations

were carried out in domestic microwave oven Samsung 30 N. Chalcone (0.01 mole),

malononitrile (0.01 mole) and ammonium acetate (0.08 mole) were mixed thoroughly to

form an intimate mixture. It was subjected to microwave irradiation at 600 Watt power

for 3-4 minutes with interruption after each 30 seconds. After completion of reaction is

indicated by TLC, the reaction mixture was cooled to room temperature and poured into

ice cold water. The separated solid was filtered off, dried and crystallized from alcohol

as colourless crystals (Scheme 1).

OH

O

R

CH3COONH4

CH2(CN)2

MWI

Solvent free

Conventional

8-10 hours

3-5 minutes

OH

N

CN

NH2

R

(1a-g) (2a-g)

Results and Discussion

New 2-amino-4-aryl-3-cyano-6-(4’-hydroxy phenyl)-pyridines were prepared by both MWI

and conventional heating. The product obtained were characterized on the basis of their

analytical and spectral data (Table 1 & 2) and the identity of compounds obtained was

checked by m.m.p. and co. TLC.

Scheme 1

Microwave Assisted Synthesis and Antimicrobial Activities 121

Table 1. Physical data of the synthesized compounds

%Yield Reaction time %N

Co

mp

d

Ar

Molecular

formula

(Mol. Wt.)

M.P

Conv MWI Conv,

h

MWI,

min. Calcd. Found

2a H C18H13N3O(287) 210 71 88 8.0 2.5 14.63 14.51

2b 4-OCH3 C19H15N3O2(317) 239 70 88 9.0 4.0 13.24 13.09

2c 3,4-(OCH3)2 C20H17N3O3(347) 25 70 85 9.0 3.0 2.10 12.01

2d 3,4,5-(OCH3)3 C21H19N3O4(377) 223 72 86 10.0 3.5 11.14 11.04

2e 4-Cl C18H12N3Cl(321.5) 64 71 87 8.0 2.5 13.06 12.98

2f 3-NO2 C18H12N4O3(332) 249 70 86 9.5 3.0 12.65 12.39

2g 4-N(CH3)2 C20H18N4O(330) 230 70 86 10.0 2.0 12.72 12.56

Table 2. Spectral data of compounds (2)

Compd Spectral data

2a IR (υ cm-1

) PMR (CDCl3,

δ ppm) : MS (FAB, m/z)

3420(OH), 3310-3300(NH2), 3080-2990

(-CH), 1480-1450(C=N, C=C) 10.50(s,

1H, OH), 7.68(s, 2H, NH2), 7.21-8.30(m,

9H, Ar) 287 M+.

(100), 286 M-1 (52),

2b IR (υ cm-1

) : PMR (CDC13,

δ ppm) :MS (FAB, m/z)

3410-3400(OH), 3305-3300(NH2), 3075-

2980(CN), 1480-1460(C=N, C=N) 3.60(s,

3H, OCH3), 8.40(s, 1H, OH), 7.71(s, 2H,

NH2), 7.3-8.21(m, 8H, Ar) 317 M+.

(100),

2c IR (υ cm-1

) PMR (CDCl3,


3422-3410(OH), 3300(NH2), 3078-2940(CN),

1495-1488(C=N, C=C) 3.60(s, 6H, OCH3),

8.90(s, 1H, Oh), 7.78(s, 3H, NH2) 7.5-8.31(m,

7H, Ar) 347 M+. (100), 346 M

+ (20)

2e IR (υ cm-1

) PMR (CDCl3,


3412-3400(OH), 3300-2996(NH2), 3080-

2995(CN), 1480-1460(C=N, C=C) 8.84(s,

1H,OH), 7.94(s, 2H, NH2), 7.40-8.42(m,

8H, Ar) 323 M+2 (40), 321 M+.

(60),

2g IR (υ cm-1

) PMR (CDCl3,


3400-3370(OH), 3310(NH2), 3085-2981

(CN), 1485-1470(C=N, C=C) 2.46(s, 6H,

CH3), 8.76(S, 1H, OH), 8.46(s, 2H, NH2),

7.2-8.1(m, 8H, Ar) 330 M+.

(100)

Table 3. Biological screening results of compounds (2a-g), zone of inhibition in (mm)

Antibacterial activity Antifungal activity Compound

E.coli K.pneumonae P.vulgaris B.subtilis A.niger C.albicans

2a 19 18 17 18 18 20

2b 20 18 21 20 18 20

2c 21 19 22 21 17 15

2d 15 14 16 18 18 15

2e 18 18 22 18 18 18

2f 18 16 16 16 17 18

2g 17 15 22 16 19 19

Ciprofloxange 40 40 40 40 - -

Fluncazole - - - - 40 40

122 Y.K. SRIVASTAVA et al.

The IR spectra of compounds (2) exhibited major absorption bands at 34400-3400 cm-1

(-OH str.), 3310-3260 cm-1

(-NH str.), 3080-2990 cm-1

(-CH str.) and 1480-1430 cm-1

(combined vibration of C=N, C=C). 1H NMR spectra of these compounds gave a singlet at δ

8.82 for hydroxyl proton, a singlet at 7.68 for amino proton. A multiplet at 7.21-8.30 for

aromatic proton of both the rings and a singlet at 1.2 for C-H proton were also observed. The

mass spectra (FAB) of these compounds gave the molecular ion peaks corresponding to their

molecular masses.

Antimicrobial activities screening

All newly prepared pyridines were screened in vitro for their antibacterial activities against

E.coli, K.pneumonae, P.vulgaris and B.subtilis at a concentration 250 µg/mL using ciprofloxange

as standard drug (50 µg/mL) and antifungal activity at a concentration 250 µg/mL.

The antibacterial activity was checked by measuring zone of inhibition. All the

compounds were found to be active against all strains of pathogens (Table 3). Substitution of

methoxy group in ring B of chalcones has slight enhancing effect on antibacterial activity as

indicated by compounds 2b, 2c and 2d. However increase in number of OCH3 groups has no

marked effect. The presence of 4-Cl substituent markedly enhanced the activity against

P.vulgaris (2e) whereas 3-NO2 group was shown to enhance the activity against E.coli, (2f).

Substitution of 4-NH2 group has no effect on antibacterial activity.

Antifungal Activity

Newly prepared pyridines were tested for antifungal activity against A.niger and C.albicans

at a concentration 250 µg/mL in vitro. The standard drug used was fluncazole at 50 µg/mL

concentration.

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5. Bose A K, Manhas M S, Ghosh M and Shah M, Vegesna S. Raju, Shamsher S. Bari,

Sarder N. Newaz, Bimal K. Banik, Ashok G. Chaudhary and Khaled J. Barakat J Org

Chem., 1991, 56(25), 6968-6970.

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Microwave Assisted Synthesis and Antimicrobial Activities ...Microwave Assisted Synthesis and Antimicrobial Activities of Some 2-Amino-4-aryl-3-cyano-6-(4’-hydroxy phenyl)-pyridines