ABSTRACT
____________________________
1
Part of the Ph.D. thesis work
INTRODUCTION
Triazole derivatives are the nitrogen containing heterocyclic compounds displaying a wide variety of
antitubercular7, analgesic8, anticancer9 specially antibacterial activity. It is interesting to note from chemical
literature that various indole10 and azetidinone 11,12 derivatives were also found to possess wide spectrum of
antibacterial activity. In light of above observations it was thought worthwhile to synthesized some new
substituted triazole derivatives by incorporation of indole and azetidinone moieties with the hope to get better
antibacterial agents.
The melting point of compounds were determined in open capillaries and are uncorrected. The homogeneity
of the synthesized compounds was routinely checked by thin layer chromatography on silica gel-G plates. The
IR spectra were recorded on a Beckman Acculab-10 spectrometer (ν max in cm-1) and the 1H NMR spectra
In methanolic solution of substituted aromatic acid hydrazides (1.0 mole), potassium hydroxide (1.5 mole)
and carbon di sulfide (1.0 mole) were added and stirred vigorously for 2-3 h. After stirrring excess of
hydrazine hydrate was added and the mixtures were further refluxed for 4 h. The completion of the reaction
was checked by TLC. The reaction mixtures were cooled and poured into ice water and neutralized with
concentrated HCl. The solids thus obtained were filtered, washed with water and recrystallized from
mL), 2-substituted-5-methoxyindolaldehydes (0.5 mole) were added separately in presence of glacial acetic
acid. The reaction mixtures were refluxed for 10 h. The solvents were distilled off at reduced pressure and the
solids thus obtained were recrystallized from appropriate solvents to yielded compounds 2a-2h.
To a the mixtures of compounds 2a-2h (0.08 mole) in dry ether, acetylchloride (0.16 mole) was added
dropwise with stirring separetelly. The reaction mixtures were refluxed for 5 h. The solvents were distilled off
separetelly and the reaction mixtures were poured onto crused ice. The solids thus obtained were washed with
A mixture of compounds 2a-2h (0.08 mole) in dry ether, benzoylchloride (0.16 mole) was added dropwise
with stirring separetelly. The reaction mixtures were refluxed for 6 h. Excess of solvent of each mixtures
were distilled off and poured onto crused ice. The solids thus obtained were washed with water and
A mixtures of compounds 3a-3h (0.01 mole) in dry dioxane (50 mL), the chloro acetyl chloride (0.015 mole)
was added in presence of triethylamine (0.008 mole). The reaction mixtures were stirred at 0 0C. Each
mixtures were further stirred at room temperature then kept aside for 48 h. The reaction mixtures were poured
4
into water. The solids thus obtained were filtered, dried and recrystallized from appropriate solvents to
A mixtures of compounds 4a-4h (0.01 mole) in dry dioxane (50 mL), the chloro acetyl chloride (0.015 mole)
was added in presence of triethylamine (0.008 mole). The reaction mixtures were stirred at 0 0C. Each
mixtures were further stirred at room temperature then kept aside for 50 h. The reaction mixtures were poured
into water. The solids thus obtained were filtered, dried and recrystallized from appropriate solvents.
1a. IR (KBr): 3320 (NH2), 3114 (CH aromatic), 2713 (SH), 1682 (C=N), 1612 (C-C of aromatic
ring), 1295 (N-N) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 11.30 (s, 1H, SH exchangeable
with D2O), 8.87 (s, 2H, NH2 exchangeable with D2O), 7.70-8.32 (m, 5H, ArH).
1b. IR (KBr): 3420 (OH), 3321 (NH2), 3115 (CH aromatic), 2712 (SH), 1680 (C=N), 1613 (C-C
of aromatic ring), 1296 (N-N) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 12.52 (s, 1H, OH
exchangeable with D2O), 11.39 (s 1H, SH exchangeable with D2O), 8.88 (s, 2H, NH2
exchangeable with D2O), 7.71-8.31 (m, 4H, ArH).
2a. IR (KBr): 3250 (NH straching), 3145 (CH aromatic), 2711 (SH), 1682 (C=N), 1614 (C-C of
aromatic ring), 1295 (N-N), 1228 (OCH3) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 11.37 (s,
1H, SH exchangeable with D2O), 8.81 (s, 1H, N=CH- indole), 7.72-8.32 (m, 8H, Ar-H), 7.50 (s,
1H, C=CH of pyrole ring of indole), 7.24 (s, 1H, NH exchangeable with D2O), 3.48 (s, 3H,
OCH3).
2b. IR (KBr): 3428 (OH), 3255 (NH str), 3146 (CH aromatic), 2712 (SH), 1680 (C=N), 1615
(C-C of aromatic ring), 1296 (N-N), 1230 (OCH3) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm:
12.53 (s, 1H, OH exchangeable with D2O), 11.35 (s, 1H, SH exchangeable with D2O), 8.87 (s,
1H, N=CH- indole), 7.71-8.31 (m, 7H, Ar-H), 7.55 (s, 1H, C=CH of pyrole ring of indole), 7.23
(s, 1H, NH exchangeable with D2O), 3.46 (s, 3H, OCH3).
2c. IR (KBr): 3145 (CH aromatic), 2850 (CH3 of indole), 2715 (SH), 1685 (C=N), 1618 (C-C of
aromatic ring), 1298 (N-N), 1232 (OCH3) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 11.32 (s,
1H, SH exchangeable with D2O), 8.89 (s, 1H, N=CH- indole), 7.71-8.30 (m, 8H, Ar-H), 7.21 (s,
1H, NH exchangeable with D2O), 3.43 (s, 3H, OCH3), 2.23 (s, 3H, CH3 of indole).
2d. IR (KBr): 3430 (OH), 3147 (C-H aromatic), 2854 (CH3 of indole), 2718 (SH), 1684 (C=N),
1619 (C-C of aromatic ring), 1297 (N-N), 1231 (OCH3) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
5
ppm: 12.55 (s, 1H, OH exchangeable with D2O), 11.33 (s, 1H, SH exchangeable with D2O), 8.87
(s, 1H, N=CH - indole), 7.71-8.31 (m, 7H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 3.42
(s, 3H, OCH3), 2.24 (s, 3H, CH3 of indole).
2e. IR (KBr): 3150 (CH aromatic), 2720 (SH), 1683 (C=N), 1620 (C-C of aromatic ring), 1299
(N-N), 1236 (OCH3) cm-1.1HNMR (CDCl3 + DMSO-d6) δ in ppm: 11.31 (s, 1H, SH
exchangeable with D2O), 8.85 (s, 1H, N=CH -indole), 7.70-8.31 (m, 13H, Ar-H), 7.23 (s, 1H,
NH exchangeable with D2O), 3.45 (s, 3H, OCH3).
2f. IR (KBr): 3428 (OH), 3154 (CH aromatic), 2722 (SH), 1681 (C=N), 1625 (C-C of aromatic
ring), 1296 (N-N), 1233 (OCH3) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 12.53 (s, 1H, OH
exchangeable with D2O), 11.32 (s, 1H, SH exchangeable with D2O), 8.83 (s, 1H, N=CH- indole),
7.70-8.30 (m, 12H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 3.43 (s, 3H, OCH3).
2g. IR (KBr): 3156 (CH aromatic), 2718 (SH), 1683 (C=N), 1632 (C-C of aromatic ring), 1298
(N-N), 1235 (OCH3), 760 (C-Cl) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 11.35 (s, 1H, SH
exchangeable with D2O), 8.84 (s, 1H, N=CH -indole), 7.72-8.30 (m, 12H, Ar-H), 7.24 (s, 1H,
NH exchangeable with D2O), 3.45 (s, 3H, OCH3).
2h. IR (KBr): 3426 (OH), 3158 (CH aromatic), 2720 (SH), 1685 (C=N), 1635 (C-C of aromatic
ring), 1297 (N-N), 1234 (OCH3), 763 (C-Cl) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in ppm: 12.52
(s, 1H, OH exchangeable with D2O), 11.30 (s, 1H, SH exchangeable with D2O), 8.83 (s, 1H,
N=CH- indole), 7.70-8.30 (m, 11H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 3.44 (s,
3H, OCH3).
3a. IR (KBr): 3360 (NH), 3155 (CH aromatic), 1720 (C=O), 1690 (C=N), 1638 (C-C of
aromatic ring), 1299 (N-N), 1235 (OCH3), 681 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
ppm: 8.86 (s, 1H, N=CH- indole), 7.72-8.31 (m, 8H, Ar-H), 7.55 (s, 1H, C=CH of pyrole ring of
indole), 7.20 (s, 1H, NH exchangeable with D2O), 3.45 (s, 3H, OCH3), 2.24 (s, 3H, CH3).
3b. IR (KBr): 3350 (NH), 3154 (CH aromatic), 1730 (C=O), 1689 (C=N), 1635 (C-C of
aromatic ring), 1294 (N-N), 1233 (OCH3), 685 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
ppm: 12.54 (s, 1H, OH exchangeable with D2O), 8.82 (s, 1H, N=CH- indole), 7.70-8.30 (m, 7H,
Ar-H), 7.56 (s, 1H, C=CH of pyrole ring of indole), 7.21 (s, 1H, NH exchangeable with D2O),
3.44 (s, 3H, OCH3), 2.23 (s, 3H, CH3).
3c. IR (KBr): 3355 (NH), 3159 (CH aromatic), 1735 (C=O), 1685 (C=N), 1631 (C-C of
aromatic ring), 1293 (N-N), 1237 (OCH3), 683 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
ppm: 8.81 (s, 1H, N=CH indole), 7.71-8.30 (m, 8H, Ar-H), 7.23 (s, 1H, NH exchangeable with
D2O), 3.46 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.24 (s, 3H, CH3 of indole).
3d. IR (KBr): 3431 (OH), 3342 (NH), 3157 (CH aromatic), 2880 (CH3), 1733 (C=O), 1683
(C=N), 1636 (C-C of aromatic ring), 1295 (N-N), 1231 (OCH3), 688 (C-S-C) cm-1 . 1HNMR
(CDCl3 + DMSO-d6) δ in ppm: 12.52 (s, 1H, OH exchangeable with D2O), 8.83 (s, 1H, N=CH-
6
indole), 7.70-8.31 (m, 7H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 3.42 (s, 3H, OCH3),
2.29 (s, 3H, CH3), 2.22 (s, 3H, CH3 of indole).
3e. IR (KBr): 3340 (NH), 3155 (CH aromatic), 2900 (CH3), 1731 (C=O), 1681 (C=N), 1637 (C-
C of aromatic ring), 1297 (N-N), 1233 (OCH3), 685 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6)
δ in ppm: 8.81 (s, 1H, N=CH- indole), 7.72-8.30 (m, 13H, Ar-H), 7.20 (s, 1H, NH exchangeable
with D2O), 3.45 (s, 3H, OCH3), 2.30 (s, 3H, CH3).
3f. IR (KBr): 3428 (OH), 3350 (NH), 3157 (CH aromatic), 2890 (CH3), 1732 (C=O), 1685
(C=N), 1635 (C-C of aromatic ring), 1295 (N-N), 1235 (OCH3), 681 (C-S-C) cm-1. 1HNMR
(CDCl3 + DMSO-d6) δ in ppm: 12.55 (s, 1H, OH exchangeable with D2O), 8.83 (s, 1H, N=CH-
indole), 7.70-8.30 (m, 12H, Ar-H), 7.22 (s, 1H, NH exchangeable with D2O), 3.47 (s, 3H,
OCH3), 2.27 (s, 3H, CH3).
3g. IR (KBr): 3355 (NH), 3158 (CH aromatic), 1733 (C=O), 1683 (C=N), 1625 (C-C of
aromatic ring), 1298 (N-N), 1235 (OCH3), 761 (C-Cl), 682 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 8.85 (s, 1H, N=CH- indole), 7.71-8.32 (m, 12H, Ar-H), 7.20 (s, 1H, NH
exchangeable with D2O), 3.48 (s, 3H, OCH3), 2.25 (s, 3H, CH3).
3h. IR (KBr): 3340 (NH), 3156 (CH aromatic), 1731 (C=O), 1687 (C=N), 1628 (C-C of
aromatic ring), 1291 (N-N), 1237 (OCH3), 765 (C-Cl), 683 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.53 (s, 1H, OH exchangeable with D2O), 8.82 (s, 1H, N=CH-indole),
7.70-8.30 (m, 11H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 3.44 (s, 3H, OCH3), 2.24 (s,
3H, CH3).
4a. IR (KBr): 3348 (NH), 3157 (CH aromatic), 1738 (C=O), 1686 (C=N), 1630 (C-C of
aromatic ring), 1295 (N-N), 1231 (OCH3), 687 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
ppm: 8.84 (s, 1H, N=CH- indole), 7.71-8.30 (m, 13H, Ar-H), 7.53 (s, 1H, C=CH of pyrole ring
of indole), 7.20 (s, 1H, NH exchangeable with D2O), 3.47 (s, 3H, OCH3).
4b. IR (KBr): 3429 (OH), 3346 (NH), 3158 (CH aromatic), 1736 (C=O), 1685 (C=N), 1635 (C-
C of aromatic ring), 1294 (N-N), 1232 (OCH3), 684 (C-S-C) cm-1 . 1HNMR (CDCl3 + DMSO-
d6) δ in ppm: 12.54 (s, 1H, OH exchangeable with D2O), 8.81 (s, 1H, N=CH -indole), 7.70-8.31
(m, 12H, Ar-H), 7.57 (s, 1H, C=CH of pyrole ring of indole), 7.23 (s, 1H, NH exchangeable with
D2O), 3.46 (s, 3H, OCH3).
4c. IR (KBr): 3345 (NH), 3155 (CH aromatic), 2853 (CH3), 1732 (C=O), 1684 (C=N), 1632 (C-
C of aromatic ring), 1290 (N-N), 1233 (OCH3), 685 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6)
δ in ppm: 8.82 (s, 1H, N=CH- indol), 7.70-8.30 (m, 13H, Ar-H), 7.21 (s, 1H, NH exchangeable
with D2O), 3.47 (s, 3H, OCH3), 2.24 (s, 3H, CH3 of indole).
4d. IR (KBr): 3427 (OH), 3344 (NH), 3157 (CH aromatic), 2851 (CH3), 1734 (C=O), 1683
(C=N), 1630 (C-C of aromatic ring), 1295 (N-N), 1234 (OCH3), 682 (C-S-C) cm-1. 1HNMR
(CDCl3 + DMSO-d6) δ in ppm: 12.53 (s, 1H, OH exchangeable with D2O), 8.80 (s, 1H, N=CH-
7
indole), 7.70-8.31 (m, 12H, Ar-H), 7.23 (s, 1H, NH exchangeable with D2O), 3.45 (s, 3H,
OCH3), 2.23 (s, 3H, CH3 of indole).
4e. IR (KBr): 3346 (NH), 3154 (CH aromatic), 1737 (C=O), 1685 (C=N), 1633 (C-C of
aromatic ring), 1297 (N-N), 1232 (OCH3), 681 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6) δ in
ppm: 8.81 (s, 1H, N=CH- indole), 7.71-8.32 (m, 18H, Ar-H), 7.21 (s, 1H, NH exchangeable with
D2O), 3.48 (s, 3H, OCH3).
4f. IR (KBr): 3428 (OH), 3345 (NH), 3156 (CH aromatic), 1733 (C=O), 1684 (C=N), 1631 (C-
C of aromatic ring), 1293 (N-N), 1234 (OCH3), 683 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6)
δ in ppm: 12.54 (s, 1H, OH exchangeable with D2O), 8.82 (s, 1H, N=CH- indole), 7.71-8.30 (m,
17H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 3.45 (s, 3H, OCH3).
4g. IR (KBr): 3343 (NH), 3152 (CH aromatic), 1735 (C=O), 1685 (C=N), 1636 (C-C of
aromatic ring), 1294 (N-N), 1231 (OCH3), 763 (C-Cl), 682 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 8.81 (s, 1H, N=CH- indole), 7.71-8.31 (m, 17H, Ar-H), 7.22 (s, 1H, NH
exchangeable with D2O), 3.46 (s, 3H, OCH3 ).
4h. IR (KBr): 3426 (OH), 3349 (NH), 3158 (CH aromatic), 1734 (C=O), 1686 (C=N), 1632 (C-
C of aromatic ring), 1294 (N-N), 1236 (OCH3), 760 (C-Cl), 683 (C-S-C) cm-1 . 1HNMR (CDCl3
+ DMSO-d6) δ in ppm: 12.55 (s, 1H, OH exchangeable with D2O), 8.87 (s, 1H, N=CH- indole),
7.70-8.30 (m, 16H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 3.44 (s, 3H, OCH3).
5a. IR (KBr): 3342 (NH), 3150 (CH aromatic), 1737 (C=O), 1687 (C=N), 1638 (C-C of
aromatic ring), 1295 (N-N), 1233 (OCH3), 762 (C-Cl), 680 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.70-8.31 (m, 8H, Ar-H), 7. 55 (s, 1H, C=CH of pyrole ring of indole), 7.21
(s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-CH- indole), 4.60 (d, 1H, CH-Cl), 3.45 (s,
3H, OCH3), 2.28 (s, 3H, CH3).
5b. IR (KBr): 3340 (NH), 3152 (CH aromatic), 1734 (C=O), 1681 (C=N), 1643 (C-C of
aromatic ring), 1280 (N-N), 1250 (OCH3), 761 (C-Cl), 681 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.53 ( s, 1H, OH exchangeable with D2O), 7.71-8.30 (m, 7H, Ar-H), 7.50
(s, 1H, C=CH of pyrole ring of indole), 7.23 (s, 1H, NH exchangeable with D2O), 6.76 (d, 1H,
N-CH- indole), 4.65 (d, 1H, CH-Cl), 3.43 (s, 3H, OCH3), 2.23 (s, 3H, CH3).
5c. IR (KBr): 3335 (NH), 3155 (CH aromatic), 2891 (CH3), 1735 (C=O), 1685 (C=N), 1644
(C-C of aromatic ring), 1283 (N-N), 1245 (OCH3), 760 (C-Cl), 687 (C-S-C ) cm-1. 1HNMR
(CDCl3 + DMSO-d6) δ in ppm: 7.71-8.32 (m, 8H, Ar-H), 7.21 (s, 1H, NH exchangeable with
D2O), 6.72 (d, 1H, N-CH -indole), 4.71 (d, 1H, CH-Cl), 3.40 (s, 3H, OCH3), 2.27 (s, 3H, CH3),
2.21 (s, 3H, CH3 of indole).
5d. IR (KBr): 3428 (OH), 3352 (NH), 3154 (CH aromatic), 2885 (CH3), 1754 (C=O), 1682
(C=N), 1643 (C-C of aromatic ring), 1285 (N-N), 1243 (OCH3), 763 (C-Cl), 685 (C-S-C) cm-1.
1
HNMR (CDCl3 + DMSO-d6) δ in ppm: 12.52 (s, 1H, OH exchangeable with D2O), 7.71-8.30
8
(m, 7H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-CH- indole), 4.72 (d,
1H, CH-Cl), 3.45 (s, 3H, OCH3), 2.28 (s, 3H, CH3), 2.22 (s, 3H, CH3 of indole).
5e. IR (KBr): 3382 (NH), 3155 (CH aromatic), 2891 (CH3), 1753 (C=O), 1681 (C=N), 1650 (C-
C of aromatic ring), 1289 (N-N), 1245 (OCH3), 760 (C-Cl), 687 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.70-8.32 (m, 13H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 6.71
(d, 1H, N-CH- indole), 4.62 (d, 1H, CH-Cl), 3.47 (s, 3H, OCH3), 2.27 (s, 3H, CH3).
5f. IR (KBr): 3429 (OH), 3386 (NH), 3152 (CH aromatic), 1757 (C=O), 1685 (C=N), 1636 (C-
C of aromatic ring), 1288 (N-N), 1253 (OCH3), 759 (C-Cl), 681 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.55 (s, 1H, OH exchangeable with D2O), 7.70-8.30 (m, 12H, Ar-H), 7.22
(s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-CH- indole), 4.60 (d, 1H, CH-Cl), 3.45 (s,
3H, OCH3), 2.24 (s, 3H, CH3).
5g. IR (KBr): 3372 (NH), 3157 (CH aromatic), 2891 (CH3), 1755 (C=O), 1683 (C=N), 1643 (C-
C of aromatic ring), 1284 (N-N), 1249 (OCH3), 761 (C-Cl), 688 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.71-8.32 (m, 12H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 6.71
(d, 1H, N-CH-indol), 4.61 (d, 1H, CH-Cl), 3.45 (s, 3H, OCH3), 2.26 (s, 3H, CH3).
5h. IR (KBr): 3432 (OH), 3377 (NH), 3155 (CH aromatic), 1751 (C=O), 1684 (C=N), 1640 (C-
C of aromatic ring), 1281 (N-N), 1245 (OCH3), 764 (C-Cl), 686 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.54 (s, 1H, OH exchangeable with D2O), 7.71-8.30 (m, 11H, Ar-H), 7.20
(s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-CH- indole), 4.63 (d, 1H, CH-Cl), 3.44 (s,
3H, OCH3), 2.24 (s, 3H, CH3).
6a. IR (KBr): 3382 (NH), 3157 (CH aromatic), 1757 (C=O), 1689 (C=N), 1637 (C-C of
aromatic ring), 1287 (N-N), 1249 (OCH3), 760 (C-Cl), 684 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.72-8.31 (m, 13H, Ar-H), 7.58 (s, 1H, C=CH of pyrole ring of indole),
7.23 (s, 1H, NH exchangeable with D2O), 6.71 (d, 1H, N-CH- indole), 4.64 (d, 1H, CH-Cl), 3.42
(s, 3H, OCH3).
6b. IR (KBr): 3416 (OH), 3382 (NH), 3158 (CH aromatic), 1758 (C=O), 1687 (C=N), 1635 (C-
C of aromatic ring), 1285 (N-N), 1246 (OCH3), 762 (C-Cl), 683 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.55 (s, 1H, OH exchangeable with D2O), 7.71-8.31 (m, 12H, Ar-H), 7.56
(s, 1H, C=CH of pyrole ring of indole), 7.21 (s, 1H, NH exchangeable with D2O), 6.72 (d, 1H,
N-CH- indole), 4.60 (d, 1H, CH-Cl), 3.43 (s, 3H, OCH3).
6c. IR (KBr): 3382 (NH), 3155 (CH aromatic), 2882 (CH3), 1755 (C=O), 1686 (C=N), 1634 (C-
C of aromatic ring), 1286 (N-N), 1247 (OCH3), 763 (C-Cl), 684 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.72-8.30 (m, 13H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 6.75
(d, 1H, N-CH- indole), 4.61 (d, 1H, CH-Cl), 3.45 (s, 3H, OCH3), 2.21 (s, 3H, CH3 of indole).
6d. IR (KBr): 3386 (NH), 3158 (CH aromatic), 2895 (CH3), 1754 (C=O), ), 1682 (C=N), 1635
(C-C of aromatic ring), 1288 (N-N), 1246 (OCH3), 760 (C-Cl), 683 (C-S-C) cm-1. 1HNMR
(CDCl3 + DMSO-d6) δ in ppm: 12.54 (s, 1H, OH exchangeable with D2O), 7.71-8.30 (m, 12H,
9
Ar-H), 7.22 (s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-CH-indole), 4.60 (d, 1H, CH-
Cl), 3.44 (s, 3H, OCH3), 2.27 (s, 3H, CH3 of indole).
6e. IR (KBr): 3387 (NH), 3159 (CH aromatic), 1756 (C=O), 1689 (C=N), 1644 (C-C of
aromatic ring), 1289 (N-N), 1249 (OCH3), 761 (C-Cl), 681 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 7.73-8.32 (m, 18H, Ar-H), 7.20 (s, 1H, NH exchangeable with D2O), 6.75
(d, 1H, N-CH-indole), 4.62 (d, 1H, CH-Cl), 3.46 (s, 3H, OCH3).
6f. IR (KBr): 3429 (OH), 3380 (NH), 3155 (CH aromatic), 1753 (C=O), 1682 (C=N), 1643 (C-
C of aromatic ring), 1287 (N-N), 1248 (OCH3), 762 (C-Cl), 683 (C-S-C) cm-1. 1HNMR (CDCl3 +
DMSO-d6) δ in ppm: 12.53 (s, 1H, OH exchangeable with D2O), 7.72-8.31 (m, 17H, Ar-H), 7.23
(s, 1H, NH exchangeable with D2O), 6.72 (d, 1H, N-CH-indol), 4.60 (d, 1H, CH-Cl), 3.43 (s, 3H,
OCH3).
6g. IR (KBr): 3485 (NH), 3153 (CH aromatic), 1685 (C-C of aromatic ring), 1683 (C=N), 1655
(C=O), 1286 (N-N), 1247 (OCH3), 763 (C-Cl), 684 (C-S-C) cm-1. 1HNMR (CDCl3 + DMSO-d6)
δ in ppm: 7.71-8.31 (m, 17H, Ar-H), 7.21 (s, 1H, NH exchangeable with D2O), 6.70 (d, 1H, N-
CH-indole), 4.62 (d, 1H, CH-Cl), 3.41 (s, 3H, OCH3).
6h. IR (KBr): 3487 (NH), 3429 (OH), 3152 (CH aromatic), 1684 (C-C of aromatic ring), 1681
(C=N), 1651 (C=O), 1285 (N-N), 1245 (OCH3), 761 (C-Cl), 682 (C-S-C) cm-1. 1HNMR (CDCl3
+ DMSO-d6) δ in ppm: 12.56 (s, 1H, OH exchangeable with D2O), 7.71-8.30 (m, 16H, Ar-H),
7.23 (s, 1H, NH exchangeable with D2O), 6.74 (d, 1H, N-CH-indol), 4.65 (d, 1H, CH-Cl), 3.42
(s, 3H, OCH3).
All the synthesized compounds were tested for their antibacterial activity. The effect of
unknown compounds were compared with the standard drug Ciprofloxacin and Gattifloxacin and
propylene glycol treated group served as control. All the newly synthesized compounds were also
Cup-Plate Method (CUPS): This activity was performed by following the method of Chuinckshank
et. al.13 in albino rats. Nutrient agar was poured onto the sterilized petri dishes (20-25 mL each pertri
10
dish). The poured material was allowed to set (1-1.5 h) and thereafter the “CUPS” (10 mm diameter)
were made by punching into the agar surface with a sterile cork borer and scooping out the punched
part of the agar. Into these cups the test compound solution was added with the help of sterile syringe.
The plates were incubated at 370C for 48hr and the results were noted. A solvent control (10%
DMSO in methanol) was also run to not the activity of the blank (solvent). The above said standard
Approximate lethal dose (ALD50): The LD50 was determined in albino rats weighing 100-120 gm of
either sex by the method of Smith14. The test compounds were administered by i.p. route in one group
and the same volume of propylene glycol in another group of animals consisting six rats in graded
doses. The animals were allowed to take food and water adlibidum. After 24 h of drug administration
percent mortality in each group was observed. From the data obtained ALD50 was calculated.
All the newly synthesized compounds were screened for antibacterial activity. The compounds
have shown antibacterial activity (Table IIa, IIb, IIc). Compounds 1a & 1b exhibited mild
substituted triazoles (1a & 1b) yielded compounds 2a-2h. Among the compound 2a-2h,
12mm K. pneumonia. This compound has shown moderate antibacterial activity. Resulted
compound revealed that 2a and 2b devoid of antibacterial activities. Compounds 2d, 2e, 2f and
2g exhibited mild antibacterial activity. The characteristics feature of the synthesized compound
3a-3h is ethanethioate moiety and compounds 4a-4h is benzothioate moiety. Compounds 3a,
3b, 3c, 3d, and 3g have shown mild to moderate antibacterial activity. Compound 3e was devoid
of antibacterial activity. Compounds 4b, 4c, 4d, 4e, 4f, 4g and 4h have shown less antibacterial
triethylamine yielded corresponding azetidinones 5a-5h having ethanethioate and 6a-6h having
benzothioate moiety increased the antibacterial activity. Among the compounds 5a-5h,
compound 5f exhibited good activity against E. coli and P. vulgaris. Moreovers compound 5h
vulgaris , 23 mm against K. pneumoniae. The later compound showed more potent antibacterial
activity than standard drugs, which prove that this compound is the most active compound of this
series. Compounds 5a, 5b, 5c, 5d, and 5e have shown significant antibacterial activity.
gattifloxacin. The synthesized compounds were also tested for approximate lethal dose ALD50
and were found to exhibit a higher value of ALD50 i.e. more than 1000mg/kg i.p. except
compound 5h which exhibited ALD50 of more than 2000mg/kg i.p. (maximum dose tested) thus
While considering all the newly synthesized compounds of this series we may conclude that
2 It is interesting to point out that compound 5h have more potency than the other
REFERENCES
1. Phillips O.A., Udo E.E., Abdel-Hamid M.E., Varghese R.: Synthesis and antibacterial
activity of novel 5-(4- methyl-1H-1,2,3-triazole) methyl oxazolidinones, Eur. J.
Med. Chem., 2009, 44(8), 3217-3227.
2. Gadaginamath S.G., Patil A.S.: Synthesis and antimicrobial activity of some new 2-amino-
methyl-5- (4-phenyl- -mercapto- 1,2,4- triazol-3- yl) methoxyindole derivatives, Indian J.
Chem., 1999, 38B(9), 1070-4.
5. Rani P., Srivastava V. K., Kumar A.: Synthesis and anti-inflammatory activity of
heterocyclic indole derivatives, Euro. J. Medi. Chem., 2004, 39(5), 449-452.
6. Omar A., Mohsen M.E., El-Dine, Shams A.S., Labouta I.M., El-Tombary A.A.:
Synthesis and evaluation for antimicrobial and antihistaminic properties of new
thiosemicabazide and triazole derivatives of triazolo[4,3-a]quinazolin-5(4H)-
ones. Alexandria J, Pharma, Sci., 1991, 5, 213-215.
8. Dundar Y., Cakir B., Kupeli E.,Sahin M.F., Noyanalpan N.: Synthesis of some new 1-
Acylthiosemicarbazides and 1,2,4-triazol-5-thiones and their analgesic and anti-
Inflammatory activities, Turk J. Chem., 2007, 31, 301-313.
10. Mohboobi S., Eichhorn E., Winkler M., Sellmer A., Mollmann U.: Antibacterial activity of a
novel series of 3-bromo-4-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrrolidione derivatives-An
extended structure-activity relationship study, Eur. J. Med. Chem., 2008, 43(3), 633-656.
11. Bhusare R.S. Shinde B.A. Pawar P.R. Vibhute B. Y.: Synthesis and antimicrobial activity of
heterocyclic schif bases, 4-thiazolidinones and 2-azetidinones, Indian J. Pharm. Sci.,
2004,3,228-31.
13
12. Desai K.G., Desai K.R.: Rapid and efficient synthesis of some biological active 2-
azetidinone under microwave irradiation, Indian J. Chem., 2005, 44B, 2093- 2096.
13. Chuinckshank R., Dugid J.P., Swain R.H.A.: Medical Microbiology, 1975, 2.
3-mercapto-1,2,4-triazoles (1a-b),4-(2׳-substituted-5׳-methoxy-3׳-indolylideno)-5-
R N N
N N
R SH OCH3
N
N SH N
NH2 (2a-h) R' N
(1a-b) H
14
triazoles (4a-h).
1a H - 6mm - - - >1000
2a H H - - - - >1000
2b 2-OH H - - - - >1000
2c H CH3 - - - - >1000
R N N R N N
O O
N S OCH 3 N S OCH3
N N
(3a-h) R' N R' N (4a-h)
H H
ALD50
Compound
R R׳ Bacterial growth inhibition (diameter) Mg/kg
i.p.
No.
3a H H - - 9mm - >1000
3e H C6H5 - - - - >1000
4a H H - 10mm - - >1000
4b 2-OH H - - - - >1000
4e H C6H5 - - - - >1000
3׳-indolylideno)-4׳׳-oxoazetidinyl]-3-ethanethioat-5-substituted phenyl-1,2,4-triazoles
R N N R N N
O O
N S OCH3 N S
OCH3
N
(5a-h) N
O N
Cl R' H O N (6a-h)
Cl R' H
5a H H 16mm - - - >1000
Table I. physical and analytical data of compounds 1a-1b, 2a-2h, 3a-3h,4a-4h,5a-5h, and 6a-6h.
21
R
CONHNH2
CS2 / KOH
NH2 NH2.H2 O
N N
R
N SH
NH 2
(1a-1b)
OCH 3
CHO
R' NH
N N
R
N SH OCH3
N CH
R' NH
(2a-2h)
N N N N
R R
N CH N CH
R' NH R' NH
(3a-3h) (4a-4h)
N N N N
R R
N CH SCHEME I N CH
R' NH R' NH
O Cl O Cl
(5a-5h) (6a-6h)
R = H, OH
R' = H, CH3, C6 H5, C6 H4 Cl
SCHEME I
22