Synthesis, characterization and biological evaluation of triazole and fused triazole derivatives

Article abstract of DOI:10.4067/S0717-97072011000300011

Triazole and fused heterocyclic triazole derivatives like Schiff bases, thiadiazoles, thiadiazepine, thiadiazine etc. were synthesized and characterized by IR, MS and 1H NMR. The triazole derivatives were evaluated for their antibacterial activity against

Full text of DOI:10.4067/S0717-97072011000300011

J. Chil. Chem. Soc., 56, Nº 3 (2011)
SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF TRIAZOLE AND FUSED
TRIAZOLE DERIVATIVES
JABALI J VORA*, DINESH R PATEL, NILESH V BHIMANI AND PARAG V AJUDIA
Department of Chemistry, Hemchandracharya North Gujarat University, Patan-384265
Gujarat, India.
(Received: December 6, 2010 - Accepted: June 21, 2011)
ABSTRACT
Triazole and fused heterocyclic triazole derivatives like Schiff bases, thiadiazoles, thiadiazepine, thiadiazine etc. were synthesized and characterized by IR,
MS and 1H NMR. The triazole derivatives were evaluated for their antibacterial activity against the gram-positive bacteria B. megaterium and S. aureus, the gram-
negative bacteria E. aerogenes and P. Aeruginosa using DMSO as a solvent.
INTRODUCTION
Heterocycles are in the center of research due to their versatile
application1. The triazole ring system is of particular interest especially
within the realm of medicinal chemistry because of their versatile biological
activity and clinical applications2,3. A number of triazole derivatives are
associated with good biological as well as pharmacological activities like
antibacterial4, anti-inflammatory5, antihypertensive6, antifungal7, anticancer8
and antitumor9 activity. Fused heterocyclic triazoles also possess important
clinical applications10. In addition to these important biological applications,
1,2,4-triazoles are also of great utility in preparative organic chemistry as
well as they have useful applications in agriculture11 and polymer12 industries.
Research in the field of pharmaceutical has its most important task in the
development of new better drugs and their successful introduction into clinical
practice due to bacterial resistance over old drugs and other effects. Owing
such properties by triazole derivatives lead us to synthesise new derivatives and
evaluate their antibacterial properties.
MATERIALS AND METHODS
All melting points were recorded in open capillaries and on Veergo
melting point apparatus. The 1H NMR spectra were recorded on a Bruker 300
MHz spectrometer at 300 MHz using TMS as an internal standard. The IR
spectra were recorded on a Perkin Elmer Spectrum 100 FTIR spectrometer and
the Mass spectra on a Waters Micromass Q-ft instrument. The chemicals used
are of LR grade and were obtained from the local market.
Reaction scheme II
Procedure for the synthesis of compound (I-VII)
Compound I : A mixture of 4-amino-5-(6-methylpyridin-3-yl)-4H-1,2,4-
triazole-3-thiol(0.01M) and p-methoxy benzaldehyde (0.01M) was taken in
ethanol(25 ml) and 2-3 drops of acetic acid was added and the reaction mixture
was refluxed for 10 hours. The product (I) was isolated and crystallized by
absolute alcohol. The resulting product dried and weighed.
Compound II : To a mixture of 4-amino-5-(6-methylpyridin-3-yl)-4H-
1,2,4-triazole-3-thiol(0.01M) and P-toluic acid (0.01M) was added POCl
3
(25ml) and the reaction mixture was refluxed for 10 hours, poured on to crushed
ice and the resulting solid was filtereda and washed with water. The resulting
product (II) was crystallised from ethanol and then dried and weighed.
Compound III : To a mixture of 4-amino-5-(6-methylpyridin-3-yl)-
4H-1,2,4-triazole-3-thiol(0.01M) and P-anisaldehyde(0.01M) in 50 ml
dimethylformamide, 50 mg p-toluene sulphonic acid (p-TsOH) was added and
the reaction mixture was refluxed for 10 hours, poured on to crushed ice and the
resulting solid was filtered and washed with water. The resulting product (III)
was crystallised from ethanol and then dried and weighed.
Compound IV : A mixture of 4-amino-5-(6-methylpyridin-3-yl)-4H-1,2,4-
triazole-3-thiol (0.01M), 2-chloro-3-formyl-7-methoxy quinoline (0.01M) in
dry DMF (20 ml) was added anhydrous K2CO3 (2.09 g) and refluxed at 80oC for
4 hrs. It was cooled and poured onto crushed ice. The product (IV) was isolated
and crystallised from ethanol and then dried and weighed.
Compound V : A mixture of 4-amino-5-(6-methylpyridin-3-yl)-4H-
1,2,4-triazole-3-thiol (0.01M), p-hydroxy-phenacyl bromide (0.01M) in dry
Reaction scheme I
e-mail: jaboli_vora@hotmail.com
771

J. Chil. Chem. Soc., 56, Nº 3 (2011)
methanol (50 ml) was heated under reflux condition for 5 hrs, then cooled and
neutralised with aqueous potassium carbonate solution. The product (V) was
isolated and crystallised from ethanol and then dried and weighed.
Compound VI : A mixture of 4-amino-5-(6-methylpyridin-3-yl)-4H-1,2,4-
triazole-3-thiol (0.01M) and p-toluene sulfonyl chloride (0.01M) was refluxed
in dry pyridine for 4-5 hrs. Product (VI) was isolated and crystallised from
ethanol and then dried and weighed.
Compound VII : A mixture of p-methylbenzoylchloride (0.01 mol) and
4-amino-5-(6-methylpyridin-3-yl)-4H-1,2,4-triazole-3-thiol (0.01 mol ) was
refluxed in dry pyridine for 8 hrs. Product (VII) was isolated and crystallised
from ethanol and then dried and weighed.
multiplet, Ar-H), 5.76 (1H, singlet, -NH), 3.86 (3H, singlet, Ar-OCH3), 2.68
(3H, singlet, Ar-CH ).
Compound IV:3Elemental analysis : found (calcd): C, 60.88(60.95); H,
3.73 (3.77); N, 22.40 (22.45); IR (KBr, cm-1): 3001 (Ar-C-H str.), 2956 (-C-
H str.), 1636 (-C=N str.), 1621 (triazole -C=N str.), 1588 (-C=C str.), 1069
(-C-O-C str.), 648 (-C-S str.). MS: 374[M.]; 1H NMR (ppm)(CDCl3): 7.90-9.42
(4H, multiplet, Ar-H), 7.45 (1H, singlet, thiadiazepine-CH), 7.26-7.34 (3H,
multiplet, Ar-H) 4.0 (3H, singlet, Ar-OCH3).
Compound V: Elemental analysis : found (calcd): C, 59.34(59.43); H, 4.03
(4.05); N, 21.60 (21.66); IR (KBr, cm-1): 3417 (-OH str.), 3066 (Ar-C-H str.),
2983 (-C-H str.), 1596 (-C=N str.), 1554 (-C=C str.), 1355 (-OH ben.), 1056
1
(N-N str.), 671 (-C-S str.). MS: 323[M.]; H NMR (ppm)(CDCl3): 9.48 (1H,
Table 1 Characteristics and Yield of Synthesised compounds.
singlet, -OH), 7.01-9.14 (7H, multiplet, Ar-H), 4.26 (2H, singlet, S-CH2), 2.65
(3H, singlet, Ar-CH ).
Compound VI:3Elemental analysis : found (calcd): C, 49.76(49.84); H,
4.15 (4.18); N, 19.34 (19.38); IR (KBr, cm-1): 3410 (N-H str.), 3068 (Ar-C-H
str.), 2934 (-C-H str.), 1588 (-C=N str.), 1497 (-C=C str.), 1310 (-SO2 ben.),
Molecular
Compound
code
Molecular
formula
M.P.
(oC)
Yield
(%)
R a
valfue
weight
(g mol-1)
1
Compound I
Compound II
C16H15N5OS
C16H13N5S
325.38
307.37
222
216
69
76
0.75
0.63
1041 (N-N str.). MS: 361[M.]; H NMR (ppm)(CDCl3): 14.00 (1H, singlet,
-SH), 9.65 (1H, singlet, N-NH), 7.18-9.13 (7H, multiplet, Ar-H), 2.63 (3H,
singlet, Ar-CH3), 2.32 (3H, singlet, Ar-CH ).
Compound VII: Elemental analysis : 3found (calcd): C, 58.99(59.06); H,
4.61 (4.65); N, 21.47 (21.52); IR (KBr, cm-1): 3220 (N-H str.), 3062 (-C-H str.),
1685 (Amide-C=O str.), 1605 (-C=N str.), 1578 (-NH def.), 1020 (N-N str.).
Compound
III
Compound
IV
C16H15N5OS
C19H14N6OS
C16H13N5OS
C15H15N5O2S2
C16H15N5OS
325.38
374.41
323.37
361.44
325.38
187
150
278
181
188
69
77
71
59
82
0.64
0.54
0.70
0.62
0.61
1
MS: 325[M.]; H NMR (ppm)(CDCl3): 13.86 (1H, singlet, -SH), 9.72 (1H,
singlet, N-NH), 7.16-9.13 (7H, multiplet, Ar-H), 2.65 (3H, singlet, Ar-CH3),
2.33 (3H, singlet, Ar-CH3).
Compound V
Compound
VI
Compound
VII
Antibacterial Activity
Table 2 Antibacterial Activity of synthesised compounds.
Compound code
Antibacterial activity
Zone of inhibition
(mm)
aSolvent Systems: Acetone:Benzene(2:8)
B.megaterium
S. aureus E.aerogenes P.aeruginosa
Preparation of Plates and Microbiological Assays
The in vitro antibacterial activity of the synthesised compounds was tested
against some clinically important bacteria by the well diffusion method using
Mueller-Hinton agar No.2 as the nutrient medium. Solutions of the synthesized
compounds were prepared (10 mg ml-1) in dimethylformamide. The bacterial
strains were activated by inoculating a loop full of the test strain in to 25 ml of
nutrient broth and incubated for 24 hrs in an incubator at 37 oC. The activated
compound
21
14
14
20
14
14
19
19
15
13
18
21
14
14
14
17
21
14
15
18
17
13
16
19
I
compound
II
compound
III
compound
o
strain (0.2 ml) was inoculated in Mueller Hinton agar at 45 C. It was then
poured into Petri dishes and allowed to solidify, then 0.85 cm ditch was made
IV
compound
V
in the plates using a sterile cork borer and these were completely filled with
compound
o
the compound solution. The dishes were incubated for 24 hrs at 37 C. The
VI
experiment was repeated three times simultaneously under the same condition
for each compound and the mean value obtained for three wells was used to
calculate the inhibition zone growth. The controls were maintained for each
bacterial strain with the solvent, where pure solvent was inoculated into the
well. The inhibition zone, formed by the compounds against the particular
bacterial strain was subtracted from the control, thereby determining the
antibacterial activities of the triazole derivatives.
Com-
pound
VII
14
21
14
19
The zones of inhibition of compounds are shown in Table 2. It can be
concluded from the data that all compounds are moderately active against
all tested bacterial strains. Compounds I and IV are the most active against
B. megaterium, compounds VI and VII show the highest activity against S.
aureus and P.aeruginosa and compounds IV and V are the most active against
E.aerogenes.
RESULTS AND DISCUSSION
Table 1 shows the molecular formula, molecular weight, melting point,
percentage yield and Rf value of all synthesised compounds. The Elemental
analysis, IR, NMR and Mass spectral data are given below.
CONCLUSION
Seven new triazole derivatives were synthesized. All of them showed
moderate activity against all bacterial strains. Compounds I and IV were the
most active against B. megaterium, while compounds VI and VII showed the
highest activity against S. aureus and P.aeruginosa and compounds IV and V
were the most active against E.aerogenes.
Characterization of Compound I-VII
Compound I: Elemental analysis : found (calcd): C, 58.97(59.06); H, 4.61
(4.65); N, 21.45 (21.52); IR (KBr, cm-1): 3006 (Ar-C-H str.), 2933 (-C-H str.),
1606 (-C=N str.), 1508 (-C=C str.), 1029 (-C-O-C str.), 690 (-C-S str.). MS:
325[M.]; 1H NMR (ppm)(CDCl ): 13.81 (1H, singlet, -SH), 9.72 (1H, singlet,
N=CH), 7.00-9.13 (7H, multipl3et, Ar-H), 3.83 (3H, singlet, Ar-OCH3), 2.65
(3H, singlet, Ar-CH3).
ACKNOWLEDGEMENT
Compound II: Elemental analysis : found (calcd): C, 62.42(62.52); H,
4.23 (4.26); N, 22.72 (22.78); IR (KBr, cm-1): 3005 (Ar-C-H str.), 2849 (-C-H
str.), 1611 (-C=N str.), 1485 (-C=C str.), 1256 (-C-N str.), 671 (-C-S str.). MS:
307[M.]; H NMR (ppm)(CDCl3): 7.03-9.13 (7H, multiplet, Ar-H), 2.68 (3H,
singlet, Ar-CH3), 2.35 (3H, singlet, Ar-CH3).
Authors are thankful to head department of chemistry and biochemistry for
providing necessary facilities.
1
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Compound III: Elemental analysis : found (calcd): C, 58.96(59.06); H,
4.62 (4.65); N, 21.47 (21.52); IR (KBr, cm-1): 3234 (N-H str.), 2933 (-C-H str.),
1602 (-C=N str.), 1513 (-C=C str.), 1014 (-C-O-C str.), 676 (-C-S str.). MS:
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