Microwave assisted synthesis and antimicrobial activities of some 2-amino-4-aryl-3-cyano-6-(4'-hydroxy phenyl)-pyridines

Article abstract of DOI:10.1155/2011/984297

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.

Full text of DOI:10.1155/2011/984297

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(1), 119-122
http://www.e-journals.net
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
ys_cor121@yahoo.com
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 depressent8 and bactericidal9 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).
R
Solvent free
HO
R
MWI
HO
3-5 minutes
CH COONH
3
4
N
CH (CN)
2
2
CN
Conventional
8-10hours
O
NH2
(1a-g)
(2a-g)
Scheme 1
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.

Microwave Assisted Synthesis and Antimicrobial Activities
121
Table 1. Physical data of the synthesized compounds
Molecular
formula
(Mol. Wt.)
%Yield
Reaction time
Conv, MWI,
%N
Calcd. Found
Ar
Conv MWI
h
min.
H
C18H13N3O(287) 210 71
C19H15N3O2(317) 239 70
C20H17N3O3(347) 25 70
88
88
85
86
87
86
86
8.0
9.0
9.0
10.0
8.0
9.5
10.0
2.5 14.63 14.51
4.0 13.24 13.09
2a
2b
2c
2d
2e
2f
4-OCH3
3,4-(OCH3)2
3.0
2.10 12.01
3,4,5-(OCH3)3 C21H19N3O4(377) 223 72
3.5 11.14 11.04
2.5 13.06 12.98
3.0 12.65 12.39
2.0 12.72 12.56
4-Cl
3-NO2
C18H12N3Cl(321.5) 64 71
C18H12N4O3(332) 249 70
C20H18N4O(330) 230 70
4-N(CH3)2
2g
Table 2. Spectral data of compounds (2)
Compd
Spectral data
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),
2a
2b
2c
2e
2g
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),
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)
IR (υ cm-1) PMR (CDCl3,
δ ppm) :MS (FAB, m/z)
IR (υ cm-1) PMR (CDCl3,
δ ppm) :MS (FAB, m/z)
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),
IR (υ cm-1) PMR (CDCl3,
δ ppm) :MS (FAB, m/z)
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
E.coli K.pneumonae P.vulgaris
Antifungal activity
B.subtilis A.niger C.albicans
Compound
19
20
21
15
18
18
17
40
-
18
18
19
14
18
16
15
40
-
17
21
22
16
22
16
22
40
-
18
20
21
18
18
16
16
40
-
18
18
17
18
18
17
19
-
20
20
15
15
18
18
19
-
2a
2b
2c
2d
2e
2f
2g
Ciprofloxange
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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