Synthesis and antibacterial studies of some Novel 2-(coumarin-3-yl)-5- mercapto-1,3,4-oxadiazoles Containing 2,4,6-trisubstituted s-triazine derivatives

Article abstract of DOI:10.1080/10426500902797285

A new series of 2-(coumarin-3-yl)-5-mercapto-1,3,4-oxadiazoles based on various aryl thiourea/ureas incorporating a 1,3,5-s-triazine moiety is reported. The components of this series have been obtained by the reaction of cyanuric chloride (1) with 2-(coum

Full text of DOI:10.1080/10426500902797285

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Antibacterial Studies
of Some Novel 2-(Coumarin-3-yl)-5-
mercapto-1,3,4-oxadiazoles Containing
2,4,6-Trisubstituted s-Triazine
Derivatives
Amit C. Patel a , Dharmesh H. Mahajan a & Kishor H. Chikhalia b
a Department of Chemistry, Veer Narmad South Gujarat University,
Surat, Gujarat, India
b Department of Chemistry, Gujarat University, Ahmedabad,
Gujarat, India
Published online: 03 Feb 2010.
To cite this article: Amit C. Patel , Dharmesh H. Mahajan & Kishor H. Chikhalia (2010) Synthesis and
Antibacterial Studies of Some Novel 2-(Coumarin-3-yl)-5-mercapto-1,3,4-oxadiazoles Containing 2,4,6-
Trisubstituted s-Triazine Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:2,
368-376
To link to this article: http://dx.doi.org/10.1080/10426500902797285
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Phosphorus, Sulfur, and Silicon, 185:368–376, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902797285
SYNTHESIS AND ANTIBACTERIAL STUDIES OF SOME
NOVEL 2-(COUMARIN-3-YL)-5-MERCAPTO-1,3,4-
OXADIAZOLES CONTAINING 2,4,6-TRISUBSTITUTED
s-TRIAZINE DERIVATIVES
Amit C. Patel,1 Dharmesh H. Mahajan,1
and Kishor H. Chikhalia2
1Department of Chemistry, Veer Narmad South Gujarat University, Surat,
Gujarat, India
2Department of Chemistry, Gujarat University, Ahmedabad, Gujarat, India
A new series of 2-(coumarin-3-yl)-5-mercapto-1,3,4-oxadiazoles based on various aryl
thiourea/ureas incorporating a 1,3,5-s-triazine moiety is reported. The components of this
series have been obtained by the reaction of cyanuric chloride (1) with 2-(coumarin-3-
yl)-5-mercapto-1,3,4-oxadiazole (2). The prepared 2-{(coumarin-3-yl-1,3,4-oxadiazolyl)-5-
thio}-4,6-dichloro-s-triazine (3) was subsequently treated with morpholine (4) to form
2-{(coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-chloro-s-triazine (5). This
was further treated with various substituted aryl urea/thioureas (6a–k/7a–k) to afford the
title compounds 8a–k and 9a–k, which were and tested for their antibacterial activity (MIC)
against different microorganisms. The structures of the novel synthesized compound have
been established on the basis of 1H NMR and FT-IR data together with elemental analysis.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Antibacterial activity (MIC); aryl urea/thiourea; 2-(coumarin-3-yl)-5-mercapto-
1,3,4-oxadiazole; 1,3,5-s-triazine
INTRODUCTION
In recent decades, coumarins have been an important class of natural and synthetic
compounds that display a wide variety of properties.1 There has been great interest in
3-carboxy coumarins that are used to synthesize modified cephalosporins,2 penicillins,3
isoureas, and amides, which exhibit specific inhibitors of α-chymotripsin and human leu-
cocyte elastase.4 They have yielded important results as antibiotics (Novobiocin and ana-
logues),5 anti-HIV agents (calonolides),6 and antitumor drugs (Calparvarin).7 Consequently,
Received 14 August 2008; accepted 4 February 2009.
The authors are very thankful to Prof. Dr. K. R. Desai, Head, Department of Chemistry, Veer Narmad
South Gujarat University, Surat, India, for providing the research facilities; one of the authors (A.C.P.) would
like to thank Dr. S. Chattopadhyay, Head, Bioorganic Division, B.A.R.C. Mumbai for 1H NMR spectra and Prof.
Dr. S. K. Menon, Gujarat University, Ahmedabad, India, for IR spectral studies.
Address correspondence to Prof. Kishor H. Chikhalia, Department of Chemistry, Gujarat University,
Navrangpura, Ahmedabad 380 009, Gujarat, India. E-mail: chikhalia kh@yahoo.com
368

NOVEL 2-(COUMARIN-3-YL)-5-MERCAPTO-1,3,4-OXADIAZOLES
369
the synthesis specifically aimed at 3-carboxycoumarins has appeared in the literature based
on Knoevenagel and Pinner reactions.8 Several derivatives of s-triazines show antimicro-
bial,9 antibacterial,10 and herbicidal activities.11 They are also used for the treatment of HIV
infection.12,13 Several workers investigated causes for diseases due to bacteria, malaria, and
cancer.14 So, from the above literature survey, s-triazine15 has been taken as a principle
moiety. Diphenyl urea derivatives are widely used, particularly in pharmaceutical chem-
istry.16 Urea derivatives possess widespread therapeutic activities such as anribacterial,17
antimicrobial, antifungal, anticancer,18 and anticonvulsant.19 Thiourea not only contributes
antibacterial, antitubercular, or antileprotic activity, but is also reported to possess antifun-
gal as well as antiviral properties.20 Recently, thiourea derivatives have been proved as a
new class of human immunodeficiency virus type 1 (HIV-1), non-nucleoside reverse tran-
scriptase inhibitors (NNRTIs),21 found as an antagonist,22 and as high density lipoprotein
(HDL) elevating agents.23 We undertook our synthetic work, as well as structural activity
relationship (SARs), using substituted aryl ureas and aryl thioureas through s-triazine to
sulfur-linked basic pharmacophore-biheterocycles, i.e., coumarinyl mercapto oxadiazole.
In view of the adaptable chemistry of cyanuric chloride24 (2,4,6-trichloro-1,3,5-
triazine) and its reactions with various nucleophiles25 such as amines, ureas, phenols,
etc., we extend our previous investigations26 in the design of novel 2-(coumarin-3-yl)-5-
mercapto-1,3,4-oxadiazole–based triazinyl derivatives (Scheme 1). The above mentioned
pharmacological properties of coumarins aroused our interest in synthesizing several new
compounds featuring a suitable heterocycle ring, i.e., s-triazine (1) in a 2-(coumarin-3-
yl)-5-mercapto-1,3,4-oxadiazole moiety (2), which was then condensed with morpholine
(4) and various aryl ureas/thioureas (6a–k/7a–k) with the aim of obtaining more potent
pharmacologically active compounds (8a–k/9a–k).
N
N
Cl
N
N
O
S
Acetone/
10% NaHCO3
O
N
N
HS
O
+
O
N
N
Cl
N
Cl
O
O
Cl
N
Cl
2
1
3
N
N
O
S
O
O
Acetone/
10% NaHCO3
N
N
+
3
O
HN
Cl
N
N
O
4
5
N
N
H
Dioxane/
10% NaHCO3
N
NH2
O
S
N
5
+
O
R
X
O
O
X
N
N
R
6a-k , X=O
7a-k , X=S
N
N
N
H
H
8a-k , X=O
9a-k , X=S
R= H, 2-Cl, 3-Cl, 4-Cl, 2-CH3, 3-CH3, 4-CH3, 2-OCH3, 4-OCH3, 3-NO2, 4-NO2
Scheme 1 Synthetic pathway of mercapto oxadiazole containing 2,4,6,-trisubstituted s-triazine derivatives.

370
A. C. PATEL ET AL.
RESULTS AND DISCUSSION
Twenty two compounds have been synthesized in this series (Scheme 1). All the
compounds, along with starting material s-triazine, were subjected to the antimicrobial
screening program. This series contains three types of chemical linkages: thio ether linkage
between s-triazine and coumarin ring system, and the introduction of morpholino group
and various aryl ureas as the other two linkages. The physical and analytical data are shown
in Table I.
Compound 8c with 3-Cl and 8d with 4-Cl substitution to the phenyl ureido nucleus
exhibited moderately comparable antibacterial activity against Gram-positive and Gram-
negative organisms, while the other substituents 8g with 4-CH3, and 8h with 2-OCH3 to the
phenyl ureido substituents possess moderate to good activity against Gram-negative bacteria
only. The remaining compounds were found to be inactive or showed a concentration more
than 400 µg/ml.
Compounds 9a–k also contain three types of chemical linkages as, thio ether and
morpholino linkages were kept, thereby introducing new aryl thioureido linkage. The
majority of the compounds in this series show moderate antibacterial activity. 9d with 4-Cl
substitution to the phenyl thioureido nucleus and 9i with 4-OCH3 substitution to the phenyl
thioureido nucleus exhibited remarkable antibacterial activity against the tested organisms.
The other compounds 9b, 9e, and 9h with 2-Cl, 2-CH3 and 2-OCH3, respectively, to the
Table I Physical and analytical data of the synthesized compounds
Analysis% found (calcd.)
Mol.
Formula
Yield
(%)
Compd.
R
Mp◦
C
H
N
C
8a
8b
8c
8d
8e
8f
8g
8h
8i
H
2-Cl
3-Cl
4-Cl
2-CH3
3-CH3
4-CH3
2-OCH3
4-OCH3
3-NO2
4-NO2
H
2-Cl
3-Cl
4-Cl
2-CH3
3-CH3
4-CH3
2-OCH3
4-OCH3
3-NO2
4-NO2
C25H20N8O5S
68
57
62
74
68
70
79
60
80
62
66
66
58
64
74
66
63
72
64
78
67
72
124–126 54.98 (55.14) 3.68 (3.70) 20.52 (20.58)
139–142 51.68 (51.86) 3.29 (3.31) 19.28 (19.35)
128–130 51.75 (51.86) 3.28 (3.31) 19.32 (19.35)
152–155 51.73 (51.86) 3.33 (3.31) 19.30 (19.35)
177–179 55.75 (51.86) 3.95 (3.97) 19.98 (20.06)
155–158 55.78 (51.86) 3.98 (3.97) 20.03 (20.06)
186–189 55.83 (51.86) 3.96 (3.97) 20.00 (20.06)
172–174 54.23 (54.35) 3.84 (3.86) 19.46 (19.50)
158–162 54.26 (54.35) 3.88 (3.86) 19.48 (19.50)
184–187 50.78 (50.93) 3.23 (3.25) 21.29 (21.38)
192–195 50.82 (50.93) 3.22 (3.25) 21.32 (21.38)
114–117 53.34 (53.56) 3.58 (3.60) 19.91 (19.99)
132–135 50.34 (50.46) 3.20 (3.22) 18.75 (18.83)
161–163 50.39 (50.46) 3.24 (3.22) 18.78 (18.83)
156–158 50.40 (50.46) 3.21 (3.22) 18.80 (18.83)
168–171 54.29 (54.34) 3.84 (3.86) 19.43 (19.50)
152–154 54.26 (54.34) 3.85 (3.86) 19.45 (19.50)
188–190 54.24 (54.34) 3.83 (3.86) 19.47 (19.50)
143–146 52.73 (52.87) 3.77 (3.75) 18.92 (18.97)
158–160 52.84 (52.87) 3.73 (3.75) 18.94 (18.97)
165–168 49.46 (49.58) 3.14 (3.16) 20.78 (20.82)
187–189 49.49 (49.58) 3.15 (3.16) 20.76 (20.82)
C
C
C
25H19N8O5SCl
25H19N8O5SCl
25H19N8O5SCl
C26H22N8O5S
C26H22N8O5S
C26H22N8O5S
C26H22N8O6S
C26H22N8O6S
C25H19N9O7S
C25H19N9O7S
8j
8k
9a
9b
9c
9d
9e
9f
9g
9h
9i
C
C
C
C
25H20N8O4S2
25H19N8O4S2Cl
25H19N8O4S2Cl
25H19N8O4S2Cl
C26H22N8O4S2
C26H22N8O4S2
C26H22N8O4S2
C26H22N8O5S2
C26H22N8O5S2
C25H19N9O6S2
C25H19N9O6S2
9j
9k

NOVEL 2-(COUMARIN-3-YL)-5-MERCAPTO-1,3,4-OXADIAZOLES
371
phenyl thioureido linkage possesses moderate to good activity against Gram-negative and
Gram-positive bacteria individually. The remaining compounds showed poor or no activity,
even at concentrations of 100 µg/ml or 400 µg/ml.
A series of 2,4,6-trisubstituted s-triazines were synthesized and evaluated for their
antibacterial activity. Attempts to increase antibacterial activity by introducing substituents
at one benzene ring of substituted phenyl urea and phenyl thiourea led to different results,
depending on the nature of the position and number of the atoms or groups introduced. High
potency has been observed with halogen atom, i.e., chlorine and methyl group, especially
when placed in the ortho or para position.
The introduction of substituents, particularly nitro and halo to the phenyl ureido or
phenyl thioureido nucleus, furnished compounds with no more activity then the monosub-
stituted counter parts. The chloro and methoxy analogs were found to be endowed with
high activity and selectivity. The comparative study showed that the ureido analogs were
much active than thioureido compounds, especially against Gram-negative organisms.
EXPERIMENTAL
Melting points were recorded on a capillary melting point apparatus and are uncor-
rected. IR spectra (KBr pellets) in cm−1 were recorded on a FT Bommen IR spectropho-
tometer. 1H NMR spectra were recorded on a Hitachi 300 MHz using tetramethyl silane as
internal standard (chemical shift in δ ppm). Elemental analyses were carried out on Haraeus
Rapid Analyser. TLC (silica gel) development was performed on silica gel coated (Merck
Kiesel 60 GF-254, 0.2 mm thickness) sheets. All chemicals and solvents were of analytical
grade and used as purchased.
Coumarin 3-Carboxylic Acid Hydrazide
A mixture of coumarin 3-carboxylic acid (18.2 g, 0.1 mol) and thionyl chloride
(17.8 g, 0.15 mol) was refluxed for 1–2 h. Excess of thionyl chloride was distilled off and
cooled in an ice bath. The resulting compound was taken in methanol and immediately used
for further processing. Hydrazine hydrate (4.8 g, 0.1 mol) was added slowly with constant
stirring, and the reaction mixture was refluxed for 4–5 h. Excess solvent was removed by
distillation under reduced pressure, and the residue was poured into ice-cold water. The
resultant solid was filtered and used for the next step. Yield 86%, mp 146–149◦C.
2-(Coumarin-3-yl)-5-thio-1,3,4-oxadiazole (2)27
A mixture of coumarin 3-carboxylic acid hydrazide (20.4 g, 0.1 mol), carbon disulfide
(7.6 mL, 0.1 mol), and potassium hydroxide solution (10 mL, 0.05 mol) in methanol (82
mL) was refluxed for 6–8 h. After the completion of the reaction, the resultant mixture was
poured into crushed ice. The product was filtered, washed with water, and recrystallized
from alcohol. The progress of the reaction was monitored by TLC using acetone:toluene
(8:2) as eluent. Yield 67%, mp 162–165◦C.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4,6-dichloro-s-triazine (3)
To a stirred solution of cyanuric chloride (18.4g, 0.1 mol) in acetone (92 mL) at 0–5◦C,
the solution of 2-(coumarin-3-yl)-5-thio-1,3,4-oxadiazole (24.6 g, 0.1 mol) in acetone

372
A. C. PATEL ET AL.
(112 mL) was added, and the pH was maintained neutral by the addition of 10% sodium
bicarbonate solution. Stirring was continued at 0–5◦C for 4 h. After the completion of the
reaction, the stirring was stopped and the solution was treated with crushed ice. The solid
product obtained was filtered and dried. The progress of the reaction was monitored by TLC
using ethyl acetate:hexane (6:4) as eluent. The crude product was purified by crystallization
from absolute alcohol to get the title compound (3); Yield 82%, mp 178–180◦C.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-
6-chloro-s-triazine (5)
The solution of morpholine (0.1 mol) in acetone was added dropwise to a well-
stirred suspension of 2-{(coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4,6-dichloro-s-triazine
(39.4 g, 0.1 mol) in acetone (90.0 mL), maintaining the temperature at 45◦C. The pH was
kept neutral by the addition of 10% sodium bicarbonate solution. The temperature was
gradually raised to 50◦C over 2 h and further maintained for 2 h. After the completion
of reaction, the solution was poured in ice-cold water. The solid product was filtered and
dried. The crude product was purified by recrystallization from absolute alcohol to yield
the title compound (5); yield 78%, mp 212–214◦C.
General Procedure for the Preparation of 2-{(Coumarin-3-yl-1,3,4-
oxadiazolyl)-5-thio}-4-(morpholino)-6-(aryl ureido/thioureido)-
s-triazine (8a–k/9a–k)
A
mixture of 2-{(coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-
chloro-s-triazine (0.005 mol) and aryl urea/thiourea (0.005 mol) in dioxane (50.0 mL) was
refluxed on a heating mantle with stirring at 80–100◦C for 4 h. The pH was adjusted to
neutral by the addition of 10% NaHCO3 solution. After the completion of the reaction, the
content was added to ice-cold water. The product was filtered and dried. The crude product
was purified by recrystallization from absolute alcohol. The physical and analytical data
of the novel synthesized compounds are given in Table I.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(phenyl
ureido)-s-triazine (8a). IR (KBr) cm−1: N H str. 2800; Coumarin C O str. 1729;
C C str. (α, β-unsat.) 1697; N H def. 1604; urea C O str. 1580; Oxadiazole C N str.
1545; Morpholine C O C str. 1375; s-triazine C N str. 806. 1H NMR: δ 2.92 (t, 4H,
CH2) 3.35 (t, 4H, CH2) 6.80 to 7.82 (m, 9H, Ar H) 8.20 (s, 1H, Ar H) 9.02 (s, 1H,
Ar NH) D2O exchangeable, 9.62 (s, 1H, Ar NH).
2-{(Coumarin- 3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-chloro
phenyl ureido)-s-triazine (8b). IR (KBr) cm−1: N H str. 2803; Coumarin C O str.
1732; C C str. (α, β-unsat.) 1695; N H def. 1606; Urea C O str. 1584; Oxadiazole C N
str. 1542; Morpholine C O C str. 1373; s-triazine C N str. 808; C Cl str. in aromatic
ring 748. 1H NMR: δ 2.90 (t, 4H, CH2) 3.32 (t, 4H, CH2) 6.82 to 7.85 (m, 8H, Ar H)
8.22 (s, 1H, Ar H) 9.05 (s, 1H, Ar NH) D2O exchangeable, 9.60 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-chloro
phenyl ureido)-s-triazine (8c). IR (KBr) cm−1: N H str. 2804; Coumarin C O str.
1726; C C str. (α, β-unsat.) 1698; N H def. 1603; Urea C O str. 1578; Oxadiazole C N
str. 1540; Morpholine C O C str. 1370; s-triazine C N str. 803; C Cl str. in aromatic

NOVEL 2-(COUMARIN-3-YL)-5-MERCAPTO-1,3,4-OXADIAZOLES
373
ring 748. 1H NMR: δ 2.95 (t, 4H, CH2) 3.30 (t, 4H, CH2) 6.78 to 7.82 (m, 8H, Ar H)
8.18 (s, 1H, Ar H) 9.05 (s, 1H, Ar NH) D2O exchangeable, 9.65 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-chloro
phenyl ureido)-s-triazine (8d). IR (KBr) cm−1: N H str. 2804; Coumarin C O str.
1729; C C str. (α, β-unsat.) 1696; N H def. 1602; Urea C O str. 1583; Oxadiazole C N
str. 1548; Morpholine C O C str. 1375; s-triazine C N str. 810; C Cl str. in aromatic
ring 745. 1H NMR: δ 2.92 (t, 4H, CH2) 3.35 (t, 4H, CH2) 6.85 to 7.88 (m, 8H, Ar H)
8.20 (s, 1H, Ar H) 9.02 (s, 1H, Ar NH) D2O exchangeable, 9.62 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-methyl
phenyl ureido)-s-triazine (8e). IR (KBr) cm−1: N H str. 2807; Coumarin C O str.
1734; C C str. (α, β-unsat.) 1699; N H def. 1605; Urea C O str. 1587; Oxadiazole C N
str. 1547; C CH3 str. in aromatic ring 1385; Morpholine C O C str. 1376; s-triazine
1
C N str. 807. H NMR: δ 2.38 (s, 3H, CH2) 2.90 (t, 4H, CH2) 3.33 (t, 4H, CH2)
6.76 to 7.87 (m, 8H, Ar H) 8.23 (s, 1H, Ar H) 9.05 (s, 1H, Ar NH) D2O exchangeable,
9.66 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-methyl
phenyl ureido)-s-triazine (8f). IR (KBr) cm−1: N H str. 2802; Coumarin C O str.
1729; C C str. (α, β-unsat.) 1697; N H def. 1604; Urea C O str. 1580; Oxadiazole C N
str. 1545; C CH3 str. in aromatic ring 1383; Morpholine C O C str. 1375; s-Triazine
1
C N str. 806. H NMR: δ 2.36 (s, 3H, CH2) 2.92 (t, 4H, CH2) 3.35 (t, 4H, CH2)
6.80 to 7.82 (m, 8H, Ar H) 8.20 (s, 1H, Ar H) 9.02 (s, 1H, Ar NH) D2O exchangeable,
9.62 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-methyl
phenyl ureido)-s-triazine (8g). IR (KBr) cm−1: N H str. 2806; Coumarin C O str.
1732; C C str. (α, β-unsat.) 1695; N H def. 1608; Urea C O str. 1583; Oxadiazole C N
str. 1548; C CH3 str. in aromatic ring 1386; Morpholine C O C str. 1373; s-triazine
1
C N str. 810. H NMR: δ 2.35 (s, 3H, CH2) 2.94 (t, 4H, CH2) 3.38 (t, 4H, CH2)
6.76 to 7.90 (m, 8H, Ar H) 8.25 (s, 1H, Ar H) 9.04 (s, 1H, Ar NH) D2O exchangeable,
9.65 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-methoxy
phenyl ureido)-s-triazine (8h). IR (KBr) cm−1: N H str. 2804; Coumarin C O str.
1730; C C str. (α, β-unsat.) 1698; N H def. 1602; Urea C O str. 1585; Oxadiazole
C N str. 1549; Morpholine C O C str. 1372; C O C str. (asym.) in alkanyl ether
1243; C O C str. (sym.) in alkanyl ether 1038; s-triazine C N str. 809. 1H NMR: δ 2.42
(s, 3H, CH2) 2.90 (t, 4H, CH2) 3.32 (t, 4H, CH2) 6.84 to 7.88 (m, 8H, Ar H) 8.25
(s, 1H, Ar H) 9.06 (s, 1H, Ar NH) D2O exchangeable, 9.68 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-methoxy
phenyl ureido)-s-triazine (8i). IR (KBr) cm−1: N H str. 2805; Coumarin C O str.
1725; C C str. (α, β-unsat.) 1694; N H def. 1603; Urea C O str. 1584; Oxadiazole
C N str. 1544; Morpholine C O C str. 1373; C O C str. (asym.) in alkanyl ether
1248; C O C str. (sym.) in alkanyl ether 1034; s-triazine C N str. 806;. 1H NMR: δ 2.48
(s, 3H, CH2) 2.92 (t, 4H, CH2) 3.35 (t, 4H, CH2) 6.80 to 7.82 (m, 8H, Ar H) 8.20
(s, 1H, Ar H) 9.02 (s, 1H, Ar NH) D2O exchangeable, 9.62 (s, 1H, Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-nitro
phenyl ureido)-s-triazine (8j). IR (KBr) cm−1: N H str. 2800; Coumarin
C O str. 1729; C C str. (α, β-unsat.) 1697; N H def. 1604; Urea C O str.
1580; Oxadiazole C N str. 1545; C NO2 str. in aromatic ring 1535; Morpholine
1
C O C str. 1375; s-triazine C N str. 806. H NMR: δ 2.92 (t, 4H, CH2) 3.35

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A. C. PATEL ET AL.
(t, 4H, CH2) 6.80 to 7.82 (m, 8H, Ar H) 8.20 (s, 1H, Ar H) 9.02 (s, 1H, Ar NH) 9.62
(s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-nitro
phenyl ureido)-s-triazine (8k). IR (KBr) cm−1: N H str. 2803; Coumarin C O str.
1732; C C str. (α, β-unsat.) 1694; N H def. 1606; Urea C O str. 1583; Oxadiazole
C N str. 1548; C NO2 str. in aromatic ring 1538; Morpholine C O C str. 1373;
s-triazine C N str. 809. 1H NMR: δ 2.89 (t, 4H, CH2) 3.30 (t, 4H, CH2) 6.88 to 7.89
(m, 8H, Ar H) 8.25 (s, 1H, Ar H) 9.06 (s, 1H, Ar NH) D2O exchangeable, 9.66 (s, 1H,
Ar NH).
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(phenyl
thioureido)-s-triazine (9a). IR (KBr) cm−1: N H str. 2807; Coumarin C O str. 1725;
C C str. (α, β-unsat.) 1692; N H def. 1603; Oxadiazole C N str. 1544; Morpholine
C O C str. 1372; Thiourea C S str. 1530; s-triazine C N str. 808;. 1H NMR: δ 2.82 (t,
4H, CH2) 3.35 (t, 4H, CH2) 7.12 to 7.92 (m, 9H, Ar H) 8.08 (s, 1H, Ar H) 8.98 (s,
1H, Ar NH) 11.12 (s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-chloro
phenyl thioureido)-s-triazine (9b). IR (KBr) cm−1: N H str. 2803; Coumarin C O
str. 1723; C C str. (α, β-unsat.) 1695; N H def. 1604; Oxadiazole C N str. 1547;
Thiourea C S str. 1534; Morpholine C O C str. 1378; C Cl str. in aromatic ring 845;
s-triazine C N str. 803. 1H NMR: δ 2.88 (t, 4H, CH2) 3.37 (t, 4H, CH2) 7.16 to 7.98
(m, 8H, Ar H) 8.12 (s, 1H, Ar H) 8.95 (s, 1H, Ar NH) 11.06 (s, 1H, Ar NH) D2O
exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-chloro
phenyl thioureido)-s-triazine (9c). IR (KBr) cm−1: N H str. 2803; Coumarin C O
str. 1729; C C str. (α, β-unsat.) 1697; N H def. 1606; Oxadiazole C N str. 1542;
Thiourea C S str. 1538; Morpholine C O C str. 1372; C Cl str. in aromatic ring 843;
s-triazine C N str. 806. 1H NMR: δ 2.86 (t, 4H, CH2) 3.34 (t, 4H, CH2) 7.18 to 7.98
(m, 8H, Ar H) 8.09 (s, 1H, Ar H) 8.92 (s, 1H, Ar NH) 11.10 (s, 1H, Ar NH) D2O
exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-chloro
phenyl thioureido)-s-triazine (9d). IR (KBr) cm−1: N H str. 2805; Coumarin C O
str. 1727; C C str. (α, β-unsat.) 1695; N H def. 1608; Oxadiazole C N str. 1548;
Thiourea C S str. 1536; Morpholine C O C str. 1370; s-triazine C N str. 809; C Cl
str. in aromatic ring 847. 1H NMR: δ 2.85 (t, 4H, CH2) 3.38 (t, 4H, CH2) 7.14 to 7.96
(m, 8H, Ar H) 8.18 (s, 1H, Ar H) 8.96 (s, 1H, Ar NH) 11.14 (s, 1H, Ar NH) D2O
exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-methyl
phenyl thioureido)-s-triazine (9e). IR (KBr) cm−1: N H str. 2810; Coumarin C O
str. 1722; C C str. (α, β-unsat.) 1692; N H def. 1611; Oxadiazole C N str. 1542;
Thiourea C S str. 1539; C CH3 str. in aromatic ring 1388; Morpholine C O C str.
1379; s-triazine C N str. 810. 1H NMR: δ 2.38 (s, 3H, CH2) 2.82 (t, 4H, CH2) 3.35 (t,
4H, CH2) 7.22 to 8.16 (m, 8H, Ar H) 8.09 (s, 1H, Ar H) 8.96 (s, 1H, Ar NH) 11.07
(s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-methyl
phenyl thioureido)-s-triazine (9f). IR (KBr) cm−1: N H str. 2806; Coumarin C O
str. 1727; C C str. (α, β-unsat.) 1694; N H def. 1609; Oxadiazole C N str. 1548;
Thiourea C S str. 1534; C CH3 str. in aromatic ring 1380; Morpholine C O C str.
1
1378; s-triazine C N str. 805. H NMR: δ 2.42 (s, 3H, CH2) 2.88 (t, 4H, CH2) 3.39

NOVEL 2-(COUMARIN-3-YL)-5-MERCAPTO-1,3,4-OXADIAZOLES
375
(t, 4H, CH2) 7.20 to 8.12 (m, 8H, Ar H) 8.18 (s, 1H, Ar H) 9.02 (s, 1H, Ar NH)
11.18 (s, 1H, Ar NH) D2O exchangeable,.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-methyl
phenyl thioureido)-s-triazine (9g). IR (KBr) cm−1: N H str. 2803; Coumarin C O
str. 1729; C C str. (α, β-unsat.) 1697; N H def. 1606; Oxadiazole C N str. 1545;
Thiourea C S str. 1530; Morpholine C O C str. 1375; C CH3 str. in aromatic ring
1
1383; s-triazine C N str. 806. H NMR: δ 2.39 (s, 3H, CH2) 2.85 (t, 4H, CH2) 3.34
(t, 4H, CH2) 7.14 to 7.99 (m, 8H, Ar H); 8.09 (s, 1H, Ar H) 8.99 (s, 1H, Ar NH)
11.13 (s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(2-methoxy
phenyl thioureido)-s-triazine (9h). IR (KBr) cm−1: N H str. 2802; Coumarin C O
str. 1732; C C str. (α, β-unsat.) 1692; N H def. 1602; Oxadiazole C N str. 1543;
Thiourea C S str. 1532; Morpholine C O C str. 1372; C O C str. (asym.) in alkanyl
ether 1248; C O C str. (sym.) in alkanyl ether 1042; s-triazine C N str. 803. 1H NMR:
δ 2.48 (s, 3H, CH2) 2.89 (t, 4H, CH2) 3.45 (t, 4H, CH2) 7.16 to 7.98 (m, 8H, Ar H)
8.16 (s, 1H, Ar H) 9.03 (s, 1H, Ar NH) 11.10 (s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-methoxy
phenyl thioureido)-s-triazine (9i). IR (KBr) cm−1: N H str. 2806; Coumarin C O
str. 1725; C C str. (α, β-unsat.) 1695; N H def. 1603; Oxadiazole C N str. 1542;
Thiourea C S str. 1537; Morpholine C O C str. 1378; C O C str. (asym.) in alkanyl
ether 1247; C O C str. (sym.) in alkanyl ether 1033; s-triazine C N str. 805;. 1H NMR:
δ 2.44 (s, 3H, CH2) 2.92 (t, 4H, CH2) 3.39 (t, 4H, CH2) 7.12 to 7.98 (m, 8H, Ar H)
8.08 (s, 1H, Ar H) 8.95 (s, 1H, Ar NH) 11.12 (s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(3-nitro
phenyl thioureido)-s-triazine (9j). IR (KBr) cm−1: N H str. 2809; Coumarin C O
str. 1724; C C str. (α, β-unsat.) 1692; N H def. 1614; Oxadiazole C N str. 1540;
Thiourea C S str. 1536; C NO2 str. in aromatic ring 1532; Morpholine C O C str.
1
1372; s-triazine C N str. 804. H NMR: δ 2.37 (s, 3H, CH2) 2.86 (t, 4H, CH2) 3.38
(t, 4H, CH2) 7.16 to 7.99 (m, 8H, Ar H) 8.12 (s, 1H, Ar H) 8.98 (s, 1H, Ar NH)
11.16 (s, 1H, Ar NH) D2O exchangeable.
2-{(Coumarin-3-yl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(4-nitro
phenyl thioureido)-s-triazine (9k). IR (KBr) cm−1: N H str. 2807; Coumarin C O
str. 1725; C C str. (α, β-unsat.) 1693; N H def. 1608; Oxadiazole C N str. 1548;
Thiourea C S str. 1538; C NO2 str. in aromatic ring 1530; Morpholine C O C str.
1
1378; s-triazine C N str. 805. H NMR: δ 2.35 (s, 3H, CH2) 2.88 (t, 4H, CH2) 3.45
(t, 4H, CH2) 7.12 to 8.02 (m, 8H, Ar H) 8.09 (s, 1H, Ar H) 8.96 (s, 1H, Ar NH)
11.06 (s, 1H, Ar NH) D2O exchangeable.
In Vitro Antibacterial Activity
Antibacterial activity28 was investigated in vitro on Gram-positive and Gram–negative
bacteria. (See Table II, available online in the Supplemental Materials.)
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