Synthesis and antimicrobial activity of novel 2-(pyridin-2-yl)thieno[2,3-d] pyrimidin-4 (3H)-ones

Article abstract of DOI:10.3906/kim-1012-888

In the present study, some new 2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H) -ones derivatives (IIa-o) were synthesized. The target compounds (IIa-o) were synthesized through the acid catalyzed condensation of 2-cyano, 3-cyano, and 4-cyano-pyridines with various 2-amino-3-carbethoxythiophenes (Ia-e). All thiophene derivatives were synthesized by Gewald reaction. The structures of the newly synthesized compounds were confirmed by UV-Visible, FT-IR, 1H-NMR, and mass spectral studies. All synthesized compounds were evaluated for their antimicrobial activity against various gram-positive and gram-negative bacterial and fungal strains. Amongst the synthesized compounds IIa, IIb, IId, IIe, and IIm were found to be active. TUeBITAK.

Full text of DOI:10.3906/kim-1012-888

Turk J Chem
35 (2011) , 915 – 924.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-1012-888
Synthesis and antimicrobial activity of novel
2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4 (3H)-ones
Nitin G. HASWANI, Sanjaykumar B. BARI∗
Department of Pharmaceutical Chemistry, R.C. Patel Institute of
Pharmaceutical Education and Research, Shirpur Near Karwand Naka,
Shirpur 425 405 Dist-Dhule-INDIA
e-mails: nitin haswani@yahoo.com, nhsb2010@gmail.com
Received: 21.12.2010
In the present study, some new 2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H)-ones derivatives (IIa-o)
were synthesized. The target compounds (IIa-o) were synthesized through the acid catalyzed condensation of
2-cyano, 3-cyano, and 4-cyano-pyridines with various 2-amino-3-carbethoxythiophenes (Ia-e). All thiophene
derivatives were synthesized by Gewald reaction. The structures of the newly synthesized compounds were
confirmed by UV-Visible, FT-IR, 1 H-NMR, and mass spectral studies. All synthesized compounds were
evaluated for their antimicrobial activity against various gram-positive and gram-negative bacterial and
fungal strains. Amongst the synthesized compounds IIa, IIb, IId, IIe, and IIm were found to be active.
Key Words: Thienopyrimidine, Gewald reaction, antimicrobial activity
Introduction
A large number of thienopyrimidines are reported in the literature as virucides, bactericides, fungicides,
acaricides, and insecticides.1,2 Condensed thienopyrimidines exhibited interesting biological activities like
antibacterial,3 antihistaminic,4 analgesic, anti-inflammatory5 and anti-malarial.6 Various condensed quina-
zoline and thienopyrimidine systems were studied for their biological activities.7 A large number of tetrahy-
drobenzothieno derivatives have been reported as anticancer, antibacterial, and antifungal agents.8 Several
thienopyrimidones were also synthesized and evaluated for their anticonvulsant activity.9 To further explore
these bioactive thienopyrimidines,10 we aimed to synthesize and characterize some new substituted pyridin-
2-yl thienopyrimidine-4(3H)-one derivatives and to evaluate these compounds for antimicrobial activity. It
∗Corresponding author
915

Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
was observed that both moieties are pharmacophores showing potential antimicrobial activity. Moreover, there
are reports on antibacterial activity observed in condensed and mononuclear pyrimidines possessing pyridinyl
substituents at 2-, 4-, and 5-positions.
Experimental
All chemicals used were of laboratory grade (Qualigen, Merck). The melting points were determined by open
capillary method on a Campbel electronic apparatus and are uncorrected. The ultraviolet absorption spectra
were determined in methanol by using a Shimadzu 1601 UV-Visible double beam spectrophotometer. The IR
spectra of synthesized compounds were recorded on a Shimadzu 8400S FT-IR in potassium bromide disks. The
1 H-NMR was recorded in CDCl3 using a NMR Varian-Mercury 300 MHz spectrometer and chemical shifts are
given in units as δ ppm, downfield from tetramethylsilane (TMS) as an internal standard. Mass spectra were
obtained on an Electron Impact mass spectrometer at 70 eV ionizing beam and using a direct insertion probe.
The progress of reactions was monitored by thin layer chromatography using chloroform-methanol or
chloroform-methanol-ammonia as the solvent systems and spots were visualized after exposure to iodine vapors
or under ultraviolet (UV) light.
Synthesis of 2-amino-3-carbethoxythiophenes (Ia-e) (Table 1)
he 2-amino-3-carbethoxythiophenes were synthesized by the variant of the well-known Gewald synthesis.11−15
The following method was used to prepare thiophene-o-aminoesters (I a-e).
Table 1. 2-Amino-3-carbethoxythiophenes (Ia-e).
R1
COOC2H5
R2
NH2
S
Compound ID
R1
R2
Ia
Ib
Ic
Id
Ie
-CH3
-H
-CH3
-C2H5
-(CH2)4-
4-ClC6H4
-6H5
-H
General method16,17
The first step was carried out for prior condensation of an aldehyde or ketone (a) with an appropriate
cyanomethylene compound (b), usually under the influence of sodium or ammonium acetate to obtain α,
β-unsaturated nitrile (c) (Knoevenagel condensation product, which is otherwise known as alkylidine interme-
diate) in a suitable solvent like benzene. Water molecules formed during the reaction were removed using a
Dean-Stark condenser.
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
In the second step the alkylidine intermediate was reacted with sulfur in ethanol containing a secondary
base such as diethylamine at around 50 ◦ C to complete the preparation (Scheme 1).
O
N
O
N
COOEt
NH2
R1
R2
R1
R2
R1
R2
O
OEt
-H2O
OEt
+
Ethanol
S
+
S
Sec.amine
(a)
(b)
(c)
(I)
Scheme 1
Synthesis of ethyl 2-amino-4, 5-dimethylthiophene-3-carboxylate (Ia)
2-Butanone (0.1 mol), sulfur (0.1 mol), ethyl cyanoacetate (0.1 mol), and ethanol (20 mL) were mixed and
stirred together. To this well stirred mixture diethylamine (0.125 mol) was added dropwise for up to half an
hour and it was stirred for 3 h. The reaction mixture was kept in a refrigerator overnight. The solid separated
was filtered, and washed with chilled 50% methanol. Yield 64.7%, mp 91-92 ◦ C.
IR (KBr) cm−1 : 3155 (N-H), 2984 (CH), 1657 (COOEt); UV (MeOH) λmax: 310.4 nm
Synthesis of ethyl 2-amino-3-carbethoxy-5-ethylthiophene-3-carboxylate (Ib)
The mixture of butyraldehyde (0.1 mol), sulfur (0.1 mol), and ethyl cyanoacetate (0.1 mol) in dimethylformamide
(15.2 mL) was stirred at 50 ◦ C for 6 h. Triethylamine (0.1 mol) was added dropwise for up to half an hour and
stirring continued for another 12 h at ambient temperature. The reaction mixture was kept in a refrigerator
overnight. The solid separated was filtered the next day, and washed with 20 mL of chilled 50% methanol.
Yield 68.7%, mp 62-63 ◦ C.
IR (KBr) cm−1 : 3167 (NH), 2966 (CH), 1660 (COOEt); UV (MeOH) λmax: 305.2 nm.
Synthesis of ethyl 2-amino-4, 5, 6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate (Ic)
Cyclohexanone (0.1 mol), sulfur (0.1 mol), ethyl cyanoacetate (0.1 mol), and ethanol (20 mL) were mixed and
stirred together. To this mixture diethylamine (0.125 mol) was added dropwise for up to half an hour and
stirring continued for another 3 h at ambient temperature. The reaction mixture was kept in a refrigerator
overnight. The solid separated was filtered the next day, and washed with 20 mL of chilled 50% methanol.
Yield 88.9%, mp 110-112 ◦ C.
IR (KBr) cm−1 : 3165 (NH), 2988 (CH) 1649, (COOEt); UV (MeOH); λmax: 311.0 nm.
Synthesis of ethyl 2-amino-5-(4-chlorophenyl)thiophene-3-carboxylate (Id)
Step I
In a round-bottomed flask fitted with a Dean-Stark condenser, 4-chloroacetophenone (0.1 mol), ethyl cyanoac-
etate (0.1 mol), glacial acetic acid (0.08 mol), ammonium acetate (0.02 mol), and benzene (50 mL) were refluxed,
until the water was totally removed (slight excess of the calculated value). Benzene was distilled out thereafter
917

Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
and the reaction mixture was dissolved in dichloromethane (50 mL) and washed with NaHCO3 (10% solution),
NaCl (10% solution), and water (20 mL). The organic layer was separated and dried, and dichloromethane was
distilled out. The solid product alkylidene ethyl cyanoacetate obtained was used as such for the second step,
without purification.
Step II
The intermediate isolated in Step I (0.082 mol) was dissolved in methanol (30 mL) and reacted with sulfur
(0.082 mol) and diethylamine (0.103 mol) to yield 19.5 g crystalline product (69.23% yield), mp 102-104 ◦ C.
IR (KBr) cm−1 : 3109 (NH), 2890 (CH), 1660 (COOEt); UV (MeOH); λmax: 286.2 nm.
Synthesis of ethyl 2-amino-5-methyl-4-phenylthiophene-3-carboxylate (Ie)
Step I
Propiophenone (0.1 mol), ethyl cyanoacetate (0.1 mol), glacial acetic acid (0.08 mol), ammonium acetate (0.02
mol), and benzene (50 mL) were reacted as per the procedure described for compound Id (Method B).
Step II
The intermediate (0.08 mol) isolated was reacted with sulfur (0.08 mol) and diethylamine (0.1 mol) to yield
crystalline product yield 64.3%, mp 91-93 ◦ C.
IR (KBr) cm−1 : 3154 (NH), 2986 (CH), 1649 (COOEt); UV (MeOH); λmax: 307.8 nm.
Synthesis of 2-(pyridine-2-yl)thieno[2,3-d]pyrimidin-4(3H)-ones (II a-o) (Table 2)
The target compounds, namely 2-(pyridine-2-yl)thieno[2,3-d]pyrimidin-4(3H)-ones (II a-o), were synthe-
sized by dry HCl gas catalyzed one pot condensation of the appropriate 2-amino-3-carbethoxythiophenes (Ia-e)
and cyanopyridines (III) in excellent yields (Scheme 2).18−20
O
O
N
R1
R2
R1
R2
dry HCl gas
dioxane
OC2H5
+
NH
R3
N
NH2
R3
(Ia-e)
(III)
(II a-o)
Scheme 2
General method for the synthesis of compounds IIa-o
The mixture of the corresponding compound I, the appropriate cyanopyridine (III), and saturated solution of
HCl in dioxane (7 M) was stirred at 0-5 ◦ C for 6 h, followed by further stirring for 2 h at room temperature
and heating on a boiling water-bath for 2 h. The reaction mixture was then worked up as usual, involving
pouring on an ice-water mixture and making it alkaline with concentrated ammonium hydroxide to give the
target compounds (IIa-o).
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
Table 2. Substituted 2-(pyridine-2-yl)thieno[2,3-d]pyrimidin-4(3H)-ones(IIa-o).
O
H
N
R1
R2
R3
N
S
Compound ID
R1
R2
R3
IIa
IIb
IIc
IId
IIe
IIf
CH3-
CH3-
CH3-
H
CH3- 2-C5H4N
CH3- 3-C5H4N
CH3- 4-C5H4N
-C2H5 2-C5H4N
-C2H5 3-C5H4N
-C2H5 4-C5H4N
H
H
IIg
IIh
IIi
-(CH2)4-
-(CH2)4-
-(CH2)4-
2-C5H4N
3-C5H4N
4-C5H4N
2-C5H4N
3-C5H4N
4-C5H4N
2-C5H4N
3-C5H4N
4-C5H4N
IIj
4-ClC6H4
H
H
IIk
IIl
4-ClC6H4
4-ClC6H4
C6H5
H
IIm
IIn
IIo
CH3
CH3
CH3
C6H5
C6H5
5, 6-dimethyl-2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIa)
Yield 88%; mp 188-191 ◦ C; IR (KBr) cm−1 : 3116.75 (N-H), 2856.67 (CH), 1661.61 (CONH); UV (MeOH)
λmax: 348.0 nm; 1 H-NMR (CDCl3)δ (ppm): 7.97-8.70 (4H, m, arom.), 9.05 (1H, s, N-H), 2.22 (3H, s, CH3),
2.26 (3H, s, CH3); MS m/z (%): 258 [M+1]+
5, 6-dimethyl-2-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIb)
Yield 98%; mp 299-302 ◦ C, IR (KBr) cm−1 : 3060.11 (N-H), 2920.03 (CH), 1654.91 (CONH); UV (MeOH)
λmax : 337.0 nm; 1 H-NMR (CDCl3)δ (ppm): 9.05-8.02 (4H, m, arom.), 8.02 (1H, s, CONH), 2.25 (3H, s,
CH3), 2.26 (3H, s, CH3); MS m/z (%): 257, 258[M+1]+ , 225, 184.
5, 6-dimethyl-2-(pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIc)
Colorless crystals, Yield 79%; 342-345 ◦ C; IR (KBr) cm−1 : 3095.54 (N-H), 2958.60 (CH), 1662.52 (CONH);
UV (MeOH) λmax: 346.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.72-7.82 (4H, m, arom.), 8.74 (1H, s, CONH), 2.22
(3H, s, CH3), 2.24 (3H, s, CH3); MS m/z (%) 257, 258[M+1]+ , 225, 184.
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
6-ethyl-2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IId) Colorless crystals, Yield 76%; mp 148-151
◦ C, IR (KBr) cm−1 : 3299.98 (N-H), 2935.46 (CH), 1693.38 (CONH); UV (MeOH) λmax: 339.0 nm; 1 H-NMR
(CDCl3)δ (ppm): 8.02-7.94 (5H, m, arom.), 8.72 (1H, s, CONH), 2.22-1.20 (5H, m, aliphatic), MS m/z (%)
257, 258[M+1]+ , 225.
6-ethyl-2-(pyridin-3-yl)thieno[2,3-d] pyrimidin-4(3H)-one (IIe)
Crystalline solid, Yield 85%; mp 223-226 ◦ C, IR (KBr) cm−1 : 3064.68 (N-H), 2877.60 (CH), 1697.24 (CONH);
UV (MeOH) λmax: 328.0 nm; 1 H-NMR (CDCl3)δ (ppm): 9.02-8.01 (5H, m, arom.), 8.58 (1H, s, CONH),
2.12-1.22 (5H, m, aliphatic); MS m/z (%) 257, 258[M+1]+ , 225.
6-ethyl-2-(pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIf)
◦
Colorless crystals, Yield 78%; mp 226-229 C; IR (KBr) cm−1 : 3159.18 (N-H), 2939.31 (CH), 1650.95 (CONH);
UV (MeOH) λmax: 336.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.02-7.83 (5H, m, arom.), 8.58 (1H, s, CONH),
2.02-1.20 (5H, m, aliphatic); MS m/z (%) 257, 258[M+1]+ , 225.
2-(pyridin-2-yl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (IIg)
Fine needles, Yield 91%; mp 196-200 ◦ C; IR (KBr) cm−1 : 3309.62 (N-H), 2925.81 (CH), 1676.03 (CONH);
UV (MeOH) λmax: 355.0 nm; 1 H-NMR (CDCl3)δ (ppm): 7.97-8.70 (4H, m, arom.), 7.82 (1H, s, CONH),
2.95-2.89 (8H, m, aliphatic); MS m/z (%) 284 [M+1]+ , 252, 206.
2-(pyridin-3-yl)-5, 6, 7, 8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one (IIh)
Fine needles, Yield 97%; mp 302-305 ◦ C, IR (KBr) cm−1 : 3172.68 (N-H), 2935.45 (CH), 1647.10 (CONH);
UV (MeOH) λmax: 338.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.55-7.54 (4H, m, arom.), 7.77 (1H, s, CONH),
2.95-2.90 (8H, m, aliphatic); MS m/z (%) 284 [M+1]+ , 252, 206.
2-(pyridin-4-yl)-5, 6, 7, 8-tetrahydro[1]benzothieno[2, 3-d]pyrimidin-4(3H)-one (IIi)
Fine needles, Yield 92.35%; mp 311-314 ◦ C; IR (KBr) cm−1 : 3107.11 (N-H), 2937.38 (CH), 1654.91 (CONH);
UV (MeOH) λmax: 348.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.71-7.82 (4H, m, arom.), 7.77 (1H, s, CONH),
2.95-2.91 (8H, m, aliphatic); MS m/z (%) 284 [M+1]+ , 252, 206.
5-(4-chlorophenyl)-2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIj)
Colorless crystalline solid, Yield 91.79%; mp 303-306 ◦ C, IR (KBr) cm−1 : 3213.19 (N-H), 3076.10 (CH), 1686.67
(CONH), 779.19 (Cl); UV (MeOH) λmax: 337.5 nm; 1 H-NMR (CDCl3)δ (ppm): 7.61-8.02 (9H, m, arom.),
8.73 (1H, s, CONH); MS m/z (%) 341[M+1]+ , 343[M+2]+ , 308, 262.
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
5-(4-Chloro-phenyl)-2-(pyridin-3-yl)thieno[2, 3-d]pyrimidin-4(3H)-one (IIk)
Colorless crystalline solid, Yield 95%; mp 302-305 ◦ C; IR (KBr) cm−1 : 3069.75(N-H), 2958.60 (CH), 1649.02
(CONH), 783.05 (Cl); UV (MeOH) λmax: 330.0 nm;1 H-NMR (CDCl3)δ (ppm): 7.60-8.61 (9H, m, arom.),
8.35 (1H, s, -CONH); MS m/z (%) 341[M+1]+ , 343[M+2]+ , 308, 262.
5-(4-Chloro-phenyl)-2-(pyridin-4-yl)thieno[2, 3-d]pyrimidin-4(3H)-one (IIl)
Colorless crystalline solid, Yield 92%; mp 302-305 ◦ C, IR (KBr) cm−1 : 3089.75 (N-H), 2871.81 (CH), 1697.24
(CONH), 767.62 (Cl); UV (MeOH) λmax: 338.0 nm; 1 H-NMR (CDCl3)δ (ppm): 7.59-8.79 (9H, m, arom.),
8.76 (1H, s, CONH); MS m/z (%) 341[M+1]+ , 343[M+2]+ , 308, 262.
6-methyl-5-phenyl-2-(pyridin-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIm)
Crystalline product, Yield 84%; mp 164-167 ◦ C; IR (KBr) cm−1 : 3215.11 (N-H), 2954.74 (CH), 1674.10
(CONH); UV (MeOH) λmax: 352.0 nm; 1 H-NMR (CDCl3)δ (ppm): 9.02-8.34 (9H, m, arom.), 8.58 (1H, s,
CONH), 2.29 (3H, s, aliphatic).
MS m/z (%) 319[M+1]+ , 320, 287, 242.
6-methyl-5-phenyl-2-(pyridin-3-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIn)
Crystalline product, Yield 98%; mp 282-285 ◦ C; IR (KBr) cm−1 : 3182.33 (N-H), 2948.96 (CH), 1654.81
(CONH); UV (MeOH) λmax: 344.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.34-7.84 (9H, m, arom.), 8.61 (1H, s,
CONH), 2.28 (3H, s, aliphatic); MS m/z (%) 319, 320[M+1]+ , 287, 242.
6-methyl-5-phenyl-2-(pyridin-4-yl)thieno[2,3-d]pyrimidin-4(3H)-one (IIo)
Crystalline product, Yield 87%; mp 248-251 ◦ C, IR (KBr) cm−1 : 3176.54(N-H), 2955.57 (CH), 1658.67
(CONH); UV (MeOH) λmax: 337.0 nm; 1 H-NMR (CDCl3)δ (ppm): 8.77-7.82 (9H, m, arom.), 8.29 (1H,
s, -CONH), 2.31 (3H, s, aliphatic).
MS m/z (%) 319,320[M+1]+, 287, 242.
Antimicrobial activity
All test microorganisms were obtained from the National Chemical Laboratory, Pune, Klebsiella pneumoniae
(NCIM-2789), Staphylococcus aureus (NCIM-2079), and Pseudomonas aeruginosa (NCIM-2036); the pathogenic
microorganisms, Shigella flexneri (MTCC-1457), Shigella sonnei (MTCC-2957), Salmonella paratyphi-A (MTCC-
735), Candida albicans, and Aspergillus niger, were procured from the Microbial Type Culture Collection,
Institute of Microbial Technology, Chandigarh.
The compounds were dissolved in DMSO (20 μg/mL) and evaluated for antimicrobial activity by modified
Kirby-Bayer method.21 The original method of Kirby-Bayer was modified and, instead of disks, wells of 6 mm
(according to standards prescribed by IP, BP, and USP) were used.
Results were interpreted in terms of the diameter of the inhibition zone.
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
Antimicrobial activity was evaluated by measuring the zone of inhibition against the test organism, using
ampicillin (10 μg/mL disk) as standard drug for antibacterial and amphotericin B (10 μg/mL disk) as standard
drug for antifungal activity. DMSO served as the control.
Results and discussion
A series of novel 2-(pyridine-2-yl)thieno[2,3-d]pyrimidin-4(3H)-one derivatives (IIa-o) (Table 2) were synthesized
in good yield, characterized by different spectral studies, and their antimicrobial activities were determined
against clinically important pathogens. Compounds IIa, IIb, IId, IIe, and IIm demonstrated good inhibition
against the bacterial and fungal strains tested.
The SAR studies revealed that the presence of a long chain aliphatic substituent at position-2 of the
thiophene ring in the compounds II increases the antifungal and antibacterial activity as observed in compound
IId. Moreover, the presence of an aromatic substituent at position-1 also found to increase activity.
Physical and spectral characteristics of the compounds synthesized
2-amino-3-carbethoxythiphenes (Ia-e)
All the starting materials, o-aminocarbonylthiophenes were pale yellow to brown crystalline solids, freely soluble
in chloroform, benzene, and methanol. They were all insoluble in water. They exhibited characteristic λmax
(methanol) around 332.0 nm.
The solid state (KBr) IR spectra of these compounds revealed a characteristic peak at around 3100-3300
cm−1 (NH) and sharp carbonyl stretching vibration for the ester compound at around 1650-1700 cm−1
.
2-(pyridine-2-yl)thieno[2,3-d]pyrimidin-4(3H)-ones (IIa-o)
All the target compounds were colorless to pale yellow crystalline solids. They were irritants to the skin and
eyes. They were insoluble in water, alcohol, and benzene, and sparingly soluble in dimethylformamide.
Most of them exhibited characteristic absorption (λmax) at around 310-317 nm (methanol).
The IR spectra of all these thienopyrimidin-4-ones were characterized by (C=O) at around 1660-1700
cm−1 . Additional (C=O, ester) vibrations were also observed in the IR spectrum of the 2-nicotinate compound
(IIm) at around 1720 cm−1
.
The 1 H-NMR spectra of these compounds revealed a characteristic signal (singlet) for the 2-chloromethylene
protons at around 4.5 δ ppm. This downfield position was attributable to the deshielded nature of these protons,
due to the electronegative chloro group attached to them.
The fragmentation pattern seen in the mass spectrum of the compound IIa revealed a prominent M+
peak at m/e 284, which is observed as the base peak.
Antimicrobial activity
Some of the newly synthesized compounds were screened for their antimicrobial activity against 7 species of
microorganisms, viz. Klebsiella pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, Shigella flexneri,
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
Shigella sonnei, and Salmonella paratyphi-A, and 2 species of fungi, Candida albicans and Aspergillus niger,
by modified Kirby-Bayer method.21 Activity of each compound was compared with that of ampicillin and
amphotericin B as the standard.
Investigation of antifungal screening revealed that all tested compounds showed variable activities towards
different species of microorganisms. All these compounds were biologically active due to the presence of different
heterocycles and functional groups. Compounds IIa, IIb, IId, IIe, and IIm, showed very high activities against
7 species of bacteria and 2 species of fungi. The results are shown in Table 3.
Table 3. Biological screening data of synthesized compounds against different strains of microorganisms.
Compound ID
Microorganisms and zone of inhibition in mm
Sa Sp Pv Kp Pa Sf Ss Ca An
11 23 15 14 11 14 11 17 15
10 13 14 13 16 13 12 12 13
10 06 09 12 12 13 14 07 10
14 20 12 18 16 16 16 25 22
06 13 05 13 10 07 16 07 16
07 14 14 11 12 08 08 11 10
11 13 13 07 11 06 06 13 09
07 07 13 05 15 12 15 06 10
08 09 10 09 14 10 11 11 15
07 13 13 10 10 11 13 07 11
06 08 08 08 11 14 12 16 14
12 13 12 09 13 11 14 12 14
12 17 15 15 11 15 07 23 20
12 10 12 08 12 13 15 13 10
05 10 13 13 15 16 06 12 10
15 13 14 13 15 13 15
IIa
IIb
IIc
IId
IIe
IIf
IIg
IIh
IIi
IIj
IIk
IIl
IIm
IIn
IIo
Ampicillin
Amphotericin B
14 16
Sa: Staphylococcus aureus, Sp: Salmonella paratyphi, Pv: Protease vulgaris, Kp: Klebsiella pneumoniae, Pa: Pseu-
domonas aeruginosa, Sf: Shigella flexneri, Ss: Shigella sonnei, Ca: Candida albicans, An: Aspergillus niger. Results
were interpreted in terms of the diameter of the inhibition zone.
Very highly active = Inhibition zone > 18 mm
Highly active = Inhibition zone 13-18 mm
Moderately active = Inhibition zone 8-13 mm
Low activity = Inhibition zone < 8 mm
Acknowledgement
The authors are thankful to the Management and Principal of the Institute for providing the necessary facilities.
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Synthesis and antimicrobial activity of novel ..., N. G. HASWANI, S. B. BARI
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