Vol. 28, No. 7 (2016)
Synthesis, Characterization and Antibacterial Activity of Novel Schiff Bases 1605
and stirred at 50 °C for 1 h. The hot homogenous solution was
filtered and cooled to 5 °C to isolate the corresponding imines
(8.1-8.9) in quantitative yields.
Ethyl 1-[(E)-2-(4-methoxybenzylideneamino)phenyl]-
5-methyl-1H-pyrazole-3-carboxylate (8.1): White solid;
Yield: 80 %; m.p.: 129-130 °C; 1H NMR (400 MHz, DMSO-
d6): δ 8.80 (s, 1H), 8.38 (d, J = 7.8 Hz, 2H), 7.98 (d, J = 7.6
Hz, 2H), 7.66-7.60 (m, 1H), 7.58-7.46 (m, 3H), 6.72 (s, 1H),
4.18 (q, J = 7.6 Hz, 3H), 2.06 (s, 3H), 1.22 (t, J = 7.2 Hz, 3H);
ESI MS: m/z, 363.3 (M+1).
Ethyl 1-[(E)-2-(4-nitrobenzylideneamino)phenyl]-5-
methyl-1H-pyrazole-3-carboxylate (8.2): Yellow solid;Yield:
90 %; m.p.: 80-81 °C; 1H NMR (400 MHz, DMSO-d6): δ 8.40
(s, 1H), 6.80 (d, J = 7.6 Hz, 2H), 7.50 (d, J = 7.6 Hz, 2H),
7.66-7.60 (m, 1H), 7.58-7.46 (m, 3H), 6.72 (s, 1H), 4.22 (q, J
= 7.6 Hz, 3H), 2.10 (s, 3H), 1.24 (t, J = 7.2 Hz, 3H); ESI MS:
m/z, 379.3 (M+1).
7.28 (m, 3H), 7.14 (d, J = 6.8 Hz, 1H), 6.84 (d, J = 6.8 Hz, 1H),
6.66 (s, 1H), 6.60 (brs, 1H), 4.30 (q, J = 7.2 Hz, 2H), 2.10 (s,
3H), 1.34 (t, J = 7.2 Hz, 3H); ESI MS: m/z, 371.1 (M-1).
Ethyl 1-[(E)-2-{(benzofuran-2-yl)methyleneamino}-
phenyl]-5-methyl-1H-pyrazole-3-carboxylate (8.8): Yellow
1
solid; Yield: 90 %; m.p.: 133-134 °C; H NMR (400 MHz,
DMSO-d6): δ 7.96 (s, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.50 (d, J
= 7.2 Hz, 1H), 7.32-7.28 (m, 3H), 7.16 (d, J = 6.8 Hz, 1H),
6.84 (d, J = 6.8 Hz, 1H), 6.62 (s, 1H), 4.28 (q, J = 7.2 Hz,
2H), 2.06 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); ESI MS: m/z,
373.1 (M+1).
Ethyl 1-[(E)-2-{(quinoxalin-2-yl)methyleneamino}-
phenyl]-5-methyl-1H-pyrazole-3-carboxylate (8.9): Off-
white solid;Yield: 90 %; m.p.: 92-93 °C; IR (KBr, νmax, cm–1):
3141, 2980, 1711 (C=O), 1622 (-C=N), 1597, 1554, 1488,
1436, 1374, 1236, 1161, 1105, 1023, 973, 853, 885, 767, 660;
1H NMR (400 MHz, DMSO-d6): δ 9.18 (s, 1H, quinaxaline
ring), 8.90 (s, 1H,-N=CH-), 8.22-8.12 (m, 2H, quinaxaline
ring proton), 7.98 (d, J = 7.8 Hz, 2H, quinaxaline ring protons),
7.72 (d, J = 7.8 Hz, 2H, phenyl ring protons), 7.62-7.58 (m,
2H, phenyl ring protons), 6.75 (s, 1H, pyrazole ring proton),
4.24 (q, J = 7.6 Hz, 2H,-CH2), 2.18 (s, 3H,-CH3), 1.28 (t, J =
7.2 Hz, 3H); ESI MS: m/z, 386.3 (M+1).
Biological assay: The synthesized imine compounds 8.1-
8.9 was screened against the following pathogens (a) Esche-
richia coli (MTCC 443) and (b) Pseudomonas aeruginosa
(MTCC 424) (Gram-negative); (c) Staphylococcus aureus
(MTCC 96) and (d) Streptococcus pyogenes (MTCC 442)
(Gram-positive). The antibacterial activity of the compounds
was carried out using agar well diffusion method according to
the literature protocol [26,27]. The compounds were dissolved
in dimethyl sulphoxide at 250 µg/mL concentrations and the
standard antibacterial drug, chloramphenicol was used as the
reference antibiotic drug. The antibacterial activity was deter-
mined by zones showing complete inhibition (mm). Growth
inhibition was calculated with reference to positive control.
All the samples were taken in triplicates.
Ethyl 1-[(E)-2-(4-cyanobenzylideneamino)phenyl]-5-
methyl-1H-pyrazole-3-carboxylate (8.2): White solid;Yield:
90 %; m.p.: 80-81 °C; IR (KBr, νmax, cm–1): 3079, 2986, 1717
(C=O), 1622 (-C=N), 1501, 1432, 1377, 1298, 1233, 1156,
1
1109, 1026, 989, 951, 840, 764, 660; H NMR (400 MHz,
DMSO-d6): δ 8.70 (s, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.90 (d, J
= 7.6 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.56-7.42 (m, 3H),
6.70 (s, 1H), 4.20 (q, J = 7.6 Hz, 3H), 2.10 (s, 3H), 1.24 (t, J
= 7.6 Hz, 3H); ESI MS: m/z, 359.1 (M+1).
Ethyl 1-[(E)-2-(4-fluorobenzylideneamino)phenyl]-5-
methyl-1H-pyrazole-3-carboxylate (8.4): White solid;Yield:
90 %; m.p.: 69-70 °C; 1H NMR (400 MHz, DMSO-d6): δ 8.76
(s, 1H), 7.96 (d, J = 7.6 Hz, 2H), 7.88 (d, J = 7.6 Hz, 2H),
7.56 (t, J = 7.2 Hz, 1H), 7.50-7.52 (m, 3H), 6.72 (s, 1H), 4.22
(q, J = 7.6 Hz, 3H), 2.12 (s, 3H), 1.26 (t, J = 7.6 Hz, 3H); ESI
MS: m/z, 351.3 (M+1).
Ethyl 1-[(E)-2-{(5-nitrothiophen-2-yl)methyleneamino}-
phenyl]-5-methyl-1H-pyrazole-3-carboxylate (8.5): Pale-
yellow solid; Yield: 85 %; m.p.: 102-103 °C; IR (KBr, νmax
,
cm–1): 3098, 3050, 2962, 1720 (C=O), 1621 (-C=N), 1598,
1507, 1430, 1376, 1340, 1233, 1158, 1108, 1027, 979, 825,
766, 654; 1HMR (300 MHz, CDCl3): δ 8.42 (s, 1H), 8.58 (s,
1H), 8.06 (s, 1H), 7.62 (t, J = 7.8 Hz, 1H), 7.52-7.38 (m, 3H),
6.68 (s, 1H), 4.20 (q, J = 7.2 Hz, 2H), 2.08 (s, 3H), 1.28 (t, J
= 7.2 Hz, 3H); ESI MS: m/z, 385.3 (M+1).
RESULTS AND DISCUSSION
The synthesis of Schiff base derivatives (8.1-8.9) is given
in Scheme-I. Condensation of diethyl oxalate (2) with acetone
(1) in presence of sodium metal at room temperature for 1 h
gave ethyl 2,4-dioxopentanoate (3). Reaction of compound 3
with hydrazine hydrate at 0-5 °C for 1 h gave ethyl 5-methyl-
1H-pyrazole-3-carboxylate (4) in 87 % yield. Nucleophilic
aromatic substitution of compound 4 with 2-chloro-nitro
benzene in presence of Cs2CO3 in DMF at 90 °C for 4 h resulted
in the formation of ethyl 5-methyl-1-(2-nitrophenyl)-1H-
pyrazole-3-carboxylate (5). Hydrogenation of compound 5 in
presence of 10 % Pd/C at 40 psi gave the corresponding ethyl
1-(2-aminophenyl)-5-methyl-1H-pyrazole-3-carboxylate (6)
in 92 % yield. Condensation of 5 with aromatic and hetero-
aromatic aldehydes (7.1-7.9) in presence of sodium sulphate
at 50 °C in ethanol gave the corresponding Schiff bases (8.1-
8.9) in quantitative yields. The structural assignment of the
newly synthesized imines (8.1-8.9) was determined by the
spectroscopic techniques like 1H NMR, IR and mass spectral
data. The mass and IR spectral data of all the compounds are
in agreement with the desired molecular formulae. Also, the
Ethyl 1-[(E)-2-{(5-nitrothiophen-3-yl)methyleneamino}-
phenyl]-5-methyl-1H-pyrazole-3-carboxylate (8.6): Pale-
yellow solid; Yield: 90 %; m.p.: 111-112 °C; IR (KBr, νmax
,
cm–1): 3037, 2963, 1721 (C=O), 1621 (-C=N), 1506, 1430,
1372, 1336, 1234, 1161, 1107, 1074,1021, 983, 949, 848, 815,
1
796, 761, 675; H NMR (400 MHz, DMSO-d6): δ 8.92 (s,
1H), 8.16 (d, J = 6.8 Hz, 1H), 7.72 (d, J = 6.8 Hz, 1H), 7.68-
7.62 (m, 1H), 7.58-7.48 (m, 3 H), 6.75 (s, 1H), 4.24 (q, J =
7.2 Hz, 2H), 2.10 (s, 3H), 1.28 (t, J = 7.2 Hz, 3H); ESI MS:
m/z, 385.2 (M+1).
Ethyl 1-[(E)-2-{(1H-indol-2-yl)methyleneamino}phenyl]-
5-methyl-1H-pyrazole-3-carboxylate (8.7): Yellow solid;
Yield: 90 %; m.p.: 120-121 °C; IR (KBr, νmax, cm–1): 3450,
3336, 2929, 2820, 1729 (C=O), 1624 (-C=N), 1514, 1440,
1
1379, 1233, 1123, 1017, 876, 831, 751, 635; H NMR (400
MHz, DMSO-d6): δ 12.18 (brs, 1H), 9.98 (s, 1H), 8.30 (s,
1H), 8.10 (d, J = 7.2 Hz, 1H), 7.50 (d, J = 7.2 Hz, 1H), 7.32-