Synthesis, Characterization and Antimicrobial Activity of Some Schiff Bases of 2-Amino-N-(o-Fluorophenylcarboxamido)-4-(p-Methoxyphenyl) Thiophenes
Shivaji Bhattacharjee*, Monica Arrora, J. Saravanan, S. Mohan
Dept. of Pharmaceutical Chemistry, PES College of Pharmacy, Bangalore --560050, India
*Corresponding Author E-mail: bhattacharjee.shivaji@gmail.com
ABSTRACT:
The novel 2-amino-N-(o-fluorophenylcarboxamido)-4-(p-methoxyphenyl)-thiophene [I] was synthesized by using a pioneer method and the parent compound [I] was reacted with different substituted aryl aldehydes to obtain a series of title compounds [I a-l]. All the new title compounds were characterized by spectral data and were screened for Antimicrobial activity.
In conclusion, it can be inferred that the electron donating groups on the phenyl ring at R of the title compounds influenced the Antimicrobial activity.
KEY WORDS: Synthesis, Thiophene, Schiff Base, Characterization, Antimicrobial activity
INTRODUCTION:
In medicinal chemistry thiophene derivatives have been very well known for their therapeutic applications. The benzo[b]thiophene system often present in biologically active compounds and many examples of biological activities found for small nucleus based on the benzo[b]thiophene moiety can be referred. The literature indicated that compounds having benzo[b]thiophene nucleus possess broad range of biological activities namely anti-inflammatory1,antifungal2, analgesic3, antiallergic 4,ocular hypotensive 5, antitumor 6, alkaline phosphatise inhibitor7 and antimicrobial8 activities.
Schiff Bases attract much interest both for synthetic and biological point of view9. Thus, they can be used in the preparation of pharmaceuticals, plastics, as well as pesticides and can occur as intermediates in much enzymatic reaction. Schiff base exhibit powerful anti-inflammatory, analgesic, ulcerogenic10 antibacterial, antifungal, anti-HIV11, antimicrobial12, anticonvulsant13 activities. Meanwhile, useful pharmacological properties are also associated with presence of 5- and 6-membered heterocyclic rings in drug molecules.
This prompted us to design and prepare new 2-amino benzo[b]thiophene by adaptation of well known and versatile Gewald reaction14 and their Schiff bases where in two moieties incorporating heterocycles are linked together through azomethine (-CH=N-) grouping and to study their Antimicrobialactivity.
MATERIAL AND METHODS:
Chemicals and Instrument:
o-fluoro aniline, ethyl cyanoacetate, p-methoxy acetophenone, sulphur, 4-di methyl amino benzaldehyde,4-hydroxy benzaldehyde,2-nitro benzaldehyde, 3-nitro benzaldehyde , 3,4,5-trimethoxy benzaldehyde , 2-hydroxy benzaldehyde, 4-hydroxy 3-methoxy benzaldehyde, 2-chloro benzaldehyde, 4-methoxy benzaldehyde, 3,4-dimethoxy, 4-chloro benzaldehyde, 4-methyl benzaldehyde were obtained from local dealer.
Analytical TLC was performed on Silica plates- GF254 (Merck) with visualization by UV or iodine vapors. Melting points were determined in open capillaries on a Thermonic Melting point apparatus and are uncorrected. The IR spectra (KBr, λ Max, cm-1) were run on Perkin Elmer FTIR Spectrophotometer. 1H-NMR (in CDCl3 / DMSO-d6) spectra were recorded using AMX-400 with TMS as internal standard. MS spectra were recorded on Brucker DPX 200. Elemental analyses were performed on Carlo Erba 1108 elemental analyzer and were within ± 0.4% of theoretical values. All the chemicals used were of analytical grade.
Synthesis of 2-cyano-N-(o-fluorophenyl)-acetamide;
Condensation of equimolar o-fluoro aniline and ethyl cyanoacetate at a temperature of 1700-1800C for 7 hours and cooled overnight to yield the 2-cyano-N-(o-fluorophenyl)-acetamide. Yield 45 %.
Synthesis of 2-amino-N-(o-fluorophenylcarboxamido)-4-(p-methoxyphenyl) thiophene (I):
A mixture of para methoxy acetophenone (6gm, 0.04mol), 2-cyano-N-(o-fluorophenyl)-acetamide (6.64gm, 0.04 mol), ammonium acetate (1gm) and glacial acetic acid (2 ml) in benzene (100 ml) was refluxed for 12 hours in Dean Stark apparatus with continuous separation of water. After 12 hours the reaction mixture was cooled. On cooling the liquid reaction mixture turned to fine crystalline solid which was employed for further reaction.
To a mixture of the above crude intermediate, sulphur (0.04 mol) in ethanol (40 ml) and diethyl amine (4.0 ml) was added drop wise with stirring. The mixture was stirred for 3 hours at 4550 °C, chilled overnight and poured. Poured ice cold water on the reaction mixture drop by drop, the solid obtained was filtered washed with ethanol to yield yellow crystalline solids. Recrystallized from alcohol. Yield 40%. The figure 1 represents the scheme of the present work. The table 1 represents the physical data of the newly synthesized compounds.
General method for synthesis of 2-[(substituted benzylidene)amino]-N-(o-fluorophenylcarboxamido)-4-(p-methoxyphenyl) thiophene (I a-l ):
A mixture of the starting compound (I) (0.005 M) and the required substituted aryl aldehydes (0.005 M) in propan-2-ol (30 ml) and catalytic amount of glacial acetic acid (2-5 drops) was heated on microwave irradiation for 2-3 minutes at 340 watts. The reaction mixture was allowed to cool. Solid obtained was filtered, washed with ethanol, dried and crystallized using DMF: Water in a ratio of (4:1) to get the pure title compounds (I a -l).
2-(4-(dimethylamino)benzylideneamino)-N-(2-fluorophenyl)-4-(4methoxyphenyl) thiophene-3-carboxamide Ia
M.P. 1200C; yield: 52%; MS: 473(100%), 395(20%), 362(60%), 340(80%) 229(30%); IR max cm-1 : 3335.82 (-NH); 3065.79 (Ar-CH); 2916.36 (Ali-CH); 1679.33 (C=O); 1620.30 (-NH bend); 1524.65 (Ar C=C); 1648.61(HC=N); 1207.15(C-F); 871.09(C-N); 751.89(C-S); 2959.13 (CH,CH3). 1HNMR(CDCl3): δ=8.6(1H,s,N=CH); 8.5 (1H,s.CONH), 7.9(2H,m,Aromatic); 7.37.5(3H,m,aromatic) 7.1-7.3(3H,m,aromatic);6.9-7.1(4H,m,aromatic) ; 6.85 (1H,s,thiophenering) ; 3.7 (3H,s,OCH3) ; 2.8(6H,s,2CH3);
13C NMR: 40.53(Cof CH3);55.9(C of OCH3);118-140(C, aromatic ring);140(2C of thiophene ring); 127(C, thiophenering); 160(C,thiophenering),163(C,CONH); 164(C,N=CH);163(C attached to F);Elemental analysis: C- 68.34%,H-5.2%,F-4%,N-8.6,O-6.8%,S-6.6%
2-(4-hydroxybenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3- carboxamide Ib
M.P. 105 0C; yield: 50%; MS:446 (80%), 340(100%), 262(50%), 151(65%); IR max cm-1: 3423.39 (OH); 3277.08 (-NH str); 3085.05 (Ar-CH); 2936.52 (Ali-CH); 1663.60 (C=O); 1600.57 (-NH bend); 1505.11 (ArC=C); 1643.67(HC=N);1215.12(C-F);872.35(C-N);756.50(C-S);
1HNMR (CDCl3): δ=8.8(1H,s,N=CH); 8.45(1H,s.CONH), 7.6-7.75(3H,m,Aromatic);7.4- 7.59 (2H,m,aromatic) ; 7.2-7.39 (4H,m,aromatic); 7-7.1(3H,m,aromatic);6.9 (1H,s, thiophene ring); 5(1H, s, OH);3.7(3H,s, OCH3); 13CNMR: 55.9(C, OCH3); 118-140(C, aromaticring); 140 (2C of thiophene ring); 127(C, thiophenering);160.3 (C of thiophene ring), 164 (C,CONH); 160(C,N=CH); 160.8(C attached to OH);163(C attached to F);
Elemental analysis: C- 67.34%, H-4.2%,F-4%,N-6.6,O-10.8%,S-7.6%
2-(2-nitrobenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Ic
M.P. 111 0C; yield: 51%; MS:475(100%), 397(70%), 364(40%) 340(80%), 286(20%); IR max cm-1: 3286.64 (-NH); 3083.76 (Ar-CH); 2940.79 (Ali-CH); 1680.00 (C=O); 1627.66 (-NH bend); 1499.90 (Ar C=C); 1648.10 (HC=N); 1218.18 (C-F); 814.20(C-N); 733.74 (C-S); 1350.12 (N-O of NO2). 1HNMR (CDCl3) : δ= 8.8(1H,s,N=CH); 8.6(1H,s.CONH), 7.5-7.7(2H,m,Aromatic); 7.4-7.9 (3H,m,aromatic); 7.0-7.4 (4H,m,aromatic); 6.9-7.0 (3H,m,aromatic); 6.91 (1H,s,thiophenering) ; 3.7(3H,s,OCH3); 13C NMR: 54.65 (C of OCH3); 118-140 (C, aromatic ring); 140.23(2Cofthiophene ring); 127.3 (C of thiophene ring); 160.3 (C of thiophene ring), 163.1 (C,CONH); 164 (C,N=CH); 163.8 (C attached to F); Elemental analysis: C- 63.19%,H-3.7%,F-4.1%,N-8.5,O-13.8%,S-6.56%
2-(3-nitrobenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Id
M.P. 113 0C; yield: 43%; MS:475 (100%), 364(50%), 286(70%); IR max cm-1: 3287.74 (-NH); 3074.32 (Ar-CH); 2940.79 (Ali-CH); 1675.00 (C=O); 1630.33 (-NH bend); 1490.56 (Ar C=C); 1668.42 (HC=N); 1215.15 (C-F); 815.15(C-N); 735.65 (C-S); 1360.01 (N-O of NO2)
1HNMR (CDCl3): δ=8.9 (1H,s,N=CH); 8.45(1H,s.CONH), 7.6-7.7 (2H,m,aromatic); 7.4-7.6 (4H,m,aromatic); 7.2-7.56 (3H,m,aromatic); 7.1-7.2 (3H,m,aromatic ); 6.92 (1H,s,thiophene ring); 3.7(3H,s,OCH3); 13C NMR: 55.65(C,OCH3);118-140(C, aromatic ring);140.5(2C of thiophene ring);127(C of thiophene ring);160.1 (C of thiophene ring), 163.5(C,CONH);164.8(C,N=CH);163.3(C attached to F);
Elemental analysis: C- 63.34%,H-3.6%,F-4.3%,N-8.5,O-13.8%,S-6.56%
2-(3,4,5-trimethoxybenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Ie
M.P. 119 0C; yield: 45%; MS:430 (100%), 250(50%), 319(80%), 241(60%);IR max cm-1 : 3332.74 (-NH); 3077.59 (Ar-CH); 2926.10 (Ali-CH); 1660.21 (C=O); 1618.26 (-NH bend); 1534.52 (Ar C=C); 1643.21 (HC=N); 1217.21(C-F); 1252.58(OCH3), 872.10(C-N);749.54(C-S);
1HNMR(CDCl3):δ=8.9(1H,s,N=CH); 8.5 (1H,s.CONH), 7.4-7.9 (5H,m,Aromatic); 7.3-7.39 (2H,m,aromatic); 7.1-7.3 (3H,m,aromatic); 6.9 (1H,s,thiophenering); 3.7 (12H,s, 3OCH3); 13CNMR:56.53 (CofOCH3); 55.9(CofOCH3); 118-140(C,aromaticring);140.3(2C,thiophene ring);127.1(C of thiophene ring);160.5 (C of thiophene ring), 163.7(C,CONH);164.1(C,N=CH);163.3(C attached to F); Elemental analysis: C- 64.54%,H-4.82%,F-3.4%,N-5.6,O-15.38%,S-6.16%
2-(2-hydroxybenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide If
M.P. 112 0C; yield: 49%; MS:446(100%), 340(85%), 229(70%)151(40%);IR max cm-1: 3423.39 (OH); 3277.08 (-NH); 3085.05 (Ar-CH); 2936.52 (Ali-CH); 1663.60 (C=O); 1600.57 (-NH bend); 1505.11 (Ar C=C); 1643.67(HC=N); 1215.12(C-F);872.35(C-N); 756.50(C-S); 1HNMR (CDCl3): =8.6(1H,s,N=CH); 8.45(1H,s.CONH), 7.6-7.7 (2H,m,Aromatic);7.3-7.58 (3H,m,aromatic); 7.1-7.3 (3H,m, aromatic); 6.9-7.1 (4H,m,aromatic); 6.8 (1H,s,thiophene ring);5.2(1H,s,OH); 3.7(3H,s,OCH3); 13C NMR:55.9(C of OCH3);118-140(C, aromatic ring);140(2C of thiophene ring);127(C of thiophene ring);160 (C of thiophene ring), 163(C,CONH);164(C,N=CH);163(C attached to F).165.1(C attached to OH);
Elemental analysis: C- 67.34%,H-4.25%,F-4.24%,N-6.6,O-10.8%,S-7.16%
2-(4-hydroxy-3-methoxybenzylideneamino)-N-(2-fluorophenyl)-4(4methoxyphenyl)thiophene-3-carboxamide Ig
M.P 107 0C; yield: 46%; MS:476 (100%), 340(70%), 365(60%), 287(50%); IR max cm-1: 3433.23 (OH); 3278.12 (-NH); 3062.99(Ar-CH); 2955.12 (Ali-CH); 1654.21 (C=O); 1615.61 (-NH bend); 1512.14 (Ar C=C); 1650.77 (HC=N); 1256.21 (OCH3) 1221.43 (C-F);875.43(C-N);754.34 (C-S); 1HNMR(CDCl3): δ=8.8(1H,s,N=CH); 8.4 (1H,s.CONH), 7.7-7.8 (2H,m,aromatic); 7.5-7.7 (2H,m, aromatic); 7.4-7.49 (2H,m,aromatic); 7.1-7.35 (2H,m, aromatic);7-7.1 (2H, m, aromatic); 6.85 (1H,s, thiophenering); 5 (1H,s,OH); 3.5 (6H,s,OCH3); 13CNMR: 57.53 (C,OCH3);55.9(C,OCH3);118-140(C, aromatic ring);140.2 (2C of thiophene ring); 127.4 (C, thiophenering); 160.4 (C, thiophene ring), 163.9 (C,CONH); 164.1 (C,N=CH) ; 163.1 (C attached to F); 160.3 (C attached to OH);
Elemental analysis: C- 65.34%,H-4.2%,F-3.44%,N-5.76,O-13.38%,S-6.76%
2-(2-chlorobenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3 carboxamide Ih
M.P. 1140C;yield:52%;MS:464(100%),353(60%),229(50%),151(70%);IR max cm-1: 3231.25 (-NH); 3056.22 (Ar-CH); 2923.32 (Ali-CH); 1667.32(C=O); 1634.12 (-NH bend ); 1523.14 (Ar C=C); 1650.41 (HC=N); 1241.28 (C-F); 831.26(C-N); 742.53 (C-S); 641.91 (C-Cl),1H NMR (CDCl3): δ=8.6(1H,s,N=CH);8.5(1H,s of amide),7.9(2H of aromatic);7.5-7.9(7H,m, aromatic) 7.1-7.5(3H,aromatic) 6.9(1H of thiophene ring); 3.7(3H,s,OCH3); 13C NMR: 55.9(C of OCH3);118-140(C, aromatic ring);140.1(2C of thiophene ring);127.3(C of thiophene ring);160.1 (C of thiophene ring), 163.3(C,CONH);164.7(C,N=CH);163(C attached to F);
Elemental analysis: C- 64.34%, H-3.2%,F-4%,N-6.6,O-6.8%,S-6.86%
2-(4-methoxybenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Ii
M.P.1090C;yield:42%;MS:460(100%),382(70%),340(50%),229(30%); IRmaxcm-1:3282.41(-NH); 3065.13 (Ar-CH); 2945.12 (Ali-CH); 1653.00 (C=O); 1613.62 (-NH bend);1518.51 (Ar C=C); 1633.43 (HC=N);1221.18 (OCH3) 1216.16 (C-F); 878.52 (C-N); 758.51(C-S); 1HNMR(CDCl3):δ=8.7(1H,s,N=CH);8.45(1H,s.CONH),7.5-7.7(2H,m,Aromatic);7.3-7.5 (3H,m,aromatic), 7.1-7.3(3H,m,aromatic) ;6.9-7.1 (4H,m,aromatic); 6.85 (1H,s,thiophene ring); 3.7 (6H,s,OCH3); 13C NMR: 53.53 (C,OCH3); 55.9(C,OCH3);118-140(C, aromatic ring); 140.1(2C of thiophene ring); 127 (C of thiophene ring) ; 160(C of thiophene ring), 163 (C,CONH) ; 164 (C,N=CH) ;163(C attached to F); Elemental analysis: C- 67.84%,H-4.52%,F-4.13%,N-6.06,O-10.8%,S-6.76%
2-(3,4-dimethoxybenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Ij
M.P. 121 0C; yield:53%; MS:490(100%), 379(50%), 329(40%), 340(70%), 150(10%); IR max cm-1: 3277.08 (-NH str); 3043.13 (Ar-CH); 2933.18 (Ali-CH); 1659.42 (C=O); 1616.61 (-NH bend);1516.23 (Ar C=C); 1653.84 (HC=N); 1243.58 (OCH3) 1215.12 (C-F); 873.61(C-N); 750.44 (C-S); 1HNMR(CDCl3): δ=8.6(1H,s,N=CH); 8.3(1H,s.CONH), 7.6-7.9 (2H,m,Aromatic); 7.4-7.55(4H,m,aromatic)7.2-7.35(3H,m,aromatic); 7.0-7.1 (2H, m, aromatic); 6.9 (1H,s,thiophenering); 3.8(9H,s,OCH3);
13CNMR: 56.53 (C,OCH3); 55.9 (C,OCH3);118-140.1 (C, aromaticring);140.4 (2C,thiophene ring); 127.4 (C, thiophene ring); 160.8 (C, thiophene ring), 163.65 (C,CONH);164.1 (C,N=CH); 163.4 (C attached to F); Elemental analysis: C- 66.14%,H-4.72%,F-3.84%,N-5.6,O-13.08%,S-6.56%
2-(4-chlorobenzylideneamino)-N-(2-fluorophenyl)-4-(4-methoxyphenyl)thiophene-3-carboxamide Ik
M.P 115 0C; yield: 48%; MS: 464(100%), 353(60%), 229(50%), 151(70%); IR max cm-1: 3213.18 (-NH); 3072.34 (Ar-CH); 2921.16 (Ali-CH); 1668.66(C=O); 1628.51 (-NH bend); 1527.21 (Ar C=C); 1656.25 (HC=N); 1241.13 (C-F); 821.89 (C-N); 789.51 (C-S); 692.71 (C-Cl).
1HNMR(CDCl3):δ=8.7(1H,s,N=CH);8.45(1H,s.CONH),7.5-7.8 (3H,m,Aromatic); 7.3- 7.5 (3H,m,aromatic); 7.1-7.3 (3H,m,aromatic); 6.9-7.1 (3H, m, aromatic ); 6.9(1H,s, thiophene ring) 3.7(3H,s,OCH3); 13CNMR: 55.9(C,OCH3); 118-140(C,aromatic ring);140(2C ,thiophene ring);127.7 (C, thiophene ring); 160.6 (C, thiophene ring), 163.5 (C,CONH); 164.7(C,N=CH);163(C attached to F);167.3(C attached to Cl);
Elemental analysis: C- 66.12%,H-4.71%,F-.79%, N-5.76, O-13.02%, S-6.53%
2-(4-methylbenzylideneamino)-N-(2-fluorophenyl)-4-(4methoxyphenyl)thiophene-3-carboxamide Il
M.P 123 0C; yield:47%; MS:460(100%), 356(70%), 245(80%),111(30%);IR max cm-1: 3256.22 (-NH); 3083.15 (Ar-CH); 2951.15 (Ali-CH); 1646.17 (C=O); 1609.84 (-NH bend); 1595.03 (Ar C=C); 1634.43(HC=N); 1252.63 (OCH3), 1262.82(C-F);873.18(C-N);755.63(C-S); 1HNMR (CDCl3):δ=8.6(1H,s,N=CH);8.5(1H,s.CONH),7.2-7.56 (3H,m,Aromatic); 7.1-7.2 (3H,m,aromatic); 7.0-7.19 (3H,m,aromatic); 6.9-7.0 (3H,m,aromatic); 6.85(1H,s, thiophene ring);3.8(6H,s,OCH3); 13CNMR:55.53 (C,OCH3); 55.9 (C,OCH3); 118-140 (C, aromatic ring); 140 (2C,thiophene ring); 127.1 (C, thiophene ring); 160 (C, thiophene ring),163.8 (C,CONH);164 (C,N=CH);163.4 (C attached to F); Elemental analysis: C- 70.34%,H-4.72%,F-4.26%,N-6.26,O-7.18%,S-7.26%.
R = 4-dimethyl amino,4-hydroxy, 2-nitro ,3-nitro,3,4,5- tri methoxy, 2-hydroxy, 4-hydroxy 3- methoxy,2-chloro, 4-methoxy, 3,4-di methoxy,4-chloro,4-methyl
Figure 1 General Experimental scheme for the synthesis of Ia-l
Table -1. Physical Data I a-l
|
Comp Code |
X |
M.P(0C) |
%Yield |
T.L.C Solvent |
Rf Value |
|
Ia |
4-di methyl amino benzaldehyde |
120 |
52 |
Methanol: Chloroform(9:1) |
0.65 |
|
Ib |
4-hydroxy benzaldehyde |
105 |
50 |
Methanol: Chloroform(9:1) |
0.73 |
|
Ic |
2-nitro benzaldehyde |
111 |
51 |
Methanol: Chloroform(9:1) |
0.65 |
|
Id |
3-nitro benzaldehyde |
113 |
43 |
Methanol: Chloroform(9:1) |
0.69 |
|
Ie |
3,4,5-trimethoxy benzaldehyde |
119 |
45 |
Methanol: Chloroform(9:1) |
0.66 |
|
If |
2-hydroxy benzaldehyde |
112 |
49 |
Methanol: Chloroform(9:1) |
0.54 |
|
Ig |
4-hydroxy 3-methoxy benzaldehyde |
107 |
46 |
Methanol: Chloroform(9:1) |
0.72 |
|
Ih |
2-chloro benzaldehyde |
114 |
52 |
Methanol: Chloroform(9:1) |
0.55 |
|
Ii |
4-methoxy benzaldehyde |
109 |
42 |
Methanol: Chloroform(9:1) |
0.67 |
|
Ij |
3,4-dimethoxy |
121 |
53 |
Methanol: Chloroform(9:1) |
0.74 |
|
Ik |
4-chloro benzaldehyde |
115 |
48 |
Methanol: Chloroform(9:1) |
0.59 |
|
Il |
4-methyl benzaldehyde |
123 |
47 |
Methanol: Chloroform(9:1) |
0.64 |
Table-2 antimicrobial activity of Schiff bases (Ia-l)
|
Comp Code |
Zone of Inhibition |
|||||
|
S.aureus |
B.subtilus |
E.Coli |
K.pneumonia |
A.niger |
C. albicans |
|
|
Ia |
12 |
14 |
NA |
NA |
NA |
NA |
|
Ib |
20 |
17 |
16 |
17 |
15 |
13 |
|
Ic |
16 |
14 |
13 |
14 |
13 |
11 |
|
Id |
18 |
16 |
16 |
14 |
11 |
12 |
|
Ie |
18 |
16 |
NA |
NA |
NA |
NA |
|
If |
15 |
14 |
NA |
NA |
13 |
12 |
|
Ig |
14 |
12 |
NA |
NA |
NA |
NA |
|
Ih |
21 |
16 |
18 |
16 |
15 |
14 |
|
Ii |
14 |
13 |
NA |
NA |
NA |
NA |
|
Ij |
12 |
11 |
14 |
17 |
NA |
NA |
|
Ik |
22 |
15 |
17 |
16 |
13 |
12 |
|
Il |
11 |
13 |
15 |
14 |
NA |
NA |
|
Ampicillin |
22 |
17 |
24 |
18 |
------ |
------- |
|
Norfloxacin |
33 |
28 |
26 |
28 |
------ |
------- |
|
Miconazole |
------- |
----- |
----- |
-------- |
30 |
27 |
Antimicrobial Activity:
Antimicrobial screening of all the synthesized compounds of the both the series were carried out by agar diffusion method at a concentration of 50mcg/0.1ml against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, Aspergillus niger and Candida albicans using DMF as solvent. The zone of inhibition was measured in the mm. and reported in the corresponding table 2.
RESULTS:
From the antibacterial screening results it was observed that, the compound with 4- hydroxy benzylidene substitution, with 2-chloro benzylidene substitution and with 4-chloro benzylidene substitution showed almost comparable antibacterial activity against both gram-positive organisms (Staphylococcus aureus and Bacillus subtilis) and gram-negative organisms (Escherichia coli and Klebsiella )compared to ampicillin. Whereas the other compounds of the series showed moderate to mild activity against gram-positive and gram-negative organisms, with respect to the standards. The antifungal screening was carried out using Aspergillus niger and Candida albicans as the test organisms. Miconazole was used as the standard. None of the synthesized compounds exhibited comparable results to that of the standard.
DISCUSSION AND CONCLUSION:
The formation of the starting compound was confirmed by IR spectra where it shows NH2 peak at 3403.0 cm-1. The NMR spectrum shows a peak at δ (ppm) = 5 of free NH2 group in the compound. The IR spectra of all the Schiff bases (I a-l) show the disappearance of NH2 peak and the appearance of N=CH (Imine) peak at a range of 1690-1640 cm-1, which clearly suggest the formation of the expected compounds. The NMR spectra of the compounds show sharp singlet peak at δ (ppm) =8.9-8.5 of N=CH (Imine-H) which also further confirm the formation of the compounds of the series. The title compounds were also confirmed by Mass spectra. All the synthesized compounds shows mild to moderate antimicrobial activity compared to standard drug .
ACKNOWLEDGEMENT:
The authors are thankful to Management, PES College of Pharmacy for providing necessary facilities.
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Received on 02.10.2012 Modified on 18.10.2012
Accepted on 25.10.2012 © AJRC All right reserved
Asian J. Research Chem. 5(11): Nov., 2012; Page 1399-1404