Dimethylformamide catalyzed synthesis of novel heterocycles - Their characterization and antimicrobial evaluation

Article abstract of DOI:10.1002/jhet.1073

Indandione 1 was brominated to yield 2-bromoIndandione 2, which further reacted with substituted thiocarbamides, carbamides, 2-aminothiophenols, 2-aminophenol, and triazole to furnished 3-substituted aniline-2-thia-4-aza-6,7- benzo-8-oxo-bicyclo[3.3.0]-1(

Full text of DOI:10.1002/jhet.1073

Month 2013
Dimethylformamide Catalyzed Synthesis of Novel Heterocycles—Their
Characterization and Antimicrobial Evaluation
*
Vijay V. Dabholkar, Sunil R. Patil, and Rajesh V. Pandey
Organic Research Laboratory, Department of Chemistry, KC College, Churchgate, Mumbai 400 020, India
*
E-mail: vijaydabholkar@gmail.com
Received March 8, 2011
DOI 10.1002/jhet.1073
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
O
O
O
S
N
H
Ar
N
H
Ar
N
N
(4)
(3)
O
O
O
S
O
S
N
R
R
N
N
N
N
H
N
H
H
(6)
(5)
(7)
Indandione 1 was brominated to yield 2‐bromoIndandione 2, which further reacted with substituted
thiocarbamides, carbamides, 2‐aminothiophenols, 2‐aminophenol, and triazole to furnished 3‐substituted
aniline‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐octadiene 3, 3‐substituted aniline‐2‐oxa‐4‐
aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐octadiene 4, 2‐Thia‐5‐aza‐9‐oxo‐3,4‐(3′‐substituted) benzo‐
7,8‐benzo‐bicyclo[4.3.0]‐1(6) nonene 5, 2‐oxa‐5‐aza‐9‐oxo‐(3, 4)‐(7,8)‐dibenzo‐bicyclo[4.3.0]‐1(6)
nonene 6, 3′‐substituted‐(1′,2′,4′)triazolo[5,6‐b][indeno(2,3‐e)]‐1,3,4‐thiadiazine 7, respectively. The
structures of compounds were elucidated on the basis of spectral techniques, further the representative
compounds were screened for their antimicrobial activity.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
The title compounds 3‐(substituted)‐imino‐2‐thia‐4‐aza‐
6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐octadiene 3a–f, 3‐
(substituted)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo
[3.3.0]‐1(5),3‐octadiene 4a–f, 2‐thia‐5‐aza‐9‐oxo‐3,4‐(3′‐
substituted)benzo‐7,8‐benzo‐bicyclo[4.3.0]‐1(6) nonene 5a–
c, 2‐oxa‐5‐aza‐9‐oxo‐(3,4)‐(7,8)‐dibenzo‐bicyclo[4.3.0]‐1(6)
nonene 6 and 3‐substituted‐(1,2,4)triazolo[4,5‐b][indeno
(2,3‐e)]‐1,3,4‐thiadiazine 7a–c were synthesized by reacting
bromo compound 2 with substituted thiocarbamides
[10], carbamides [11], 2‐aminothiophenols [12, 13], 2‐
aminophenol and triazoles, respectively, in presence of
dimethylformamide (DMF) as a catalyst and ethanol as a
solvent (Scheme 1).
Heterocyclic compounds constitute the largest family
of organic compounds, regardless of structure and
functionality. Heterocyclic compounds are of particular
interest in medicinal chemistry and this has catalyzed
the discovery and development of many new heterocy-
clic compounds.
In the published reports, the compounds bearing thiazole
and oxazole moiety have been found to possess
antibacterial [1], antitubercular [2], and anti‐inflammatory
[3] activity. Similarly, heterocycles containing thiazine
and oxazine moiety are well‐known for their diverse
biological activity and play a key role as anti‐psychotic
[4], antiviral [5], and anti‐microbial agents [6]. Fused s‐
triazoles and their derivatives have been investigated for
their potential pharmacological properties such as antifun-
gal [7], antidepressant [8], and plant growth regulators
[9]. In view of the biological potential of the above
pharmacophore, syntheses of various derivatives have been
undertaken.
The structures of representative compounds were
elucidated on the basis of spectral techniques, further the
representative compounds were screened for their antimi-
crobial activity, which showed a promising activity against
gram positive as well as gram negative bacterias.
The physical characterization data was given in Table 1.
EXPERIMENTAL
RESULTS AND DISCUSSION
All chemicals were supplied by E. Merck (Germany) and S. D.
Fine Chemicals (India). Melting points of all synthesized
compounds were determined in open capillary tubes using Veego
The synthesis of 2‐bromo‐Indandione 2 was achieved
from Indandione 1 using bromine in glacial acetic acid.
© 2013 HeteroCorporation

V. V. Dabholkar, S. R. Patil, and R. V. Pandey
Vol 000
Scheme 1.
using Varian 500 MHz NMR spectrophotometer using CDCl3/
DMSO‐d6 as solvent and TMS as an internal standard. C, H, N
analyses were performed on Carlo Erba 1108 (C H N) Elemental
Analyzer.
O
O
Br2
Br
glacial acetic acid
Synthesis of 2‐bromo‐indandione, 2. Indandione 1 (0.01
mol) was dissolved in 10 mL of glacial acetic acid. A solution
of bromine (0.01 mol) in glacial acetic acid was added dropwise
with continuous stirring in presence of UV light. The stirring
was continued for 1 h. The reaction mixture was quenched into
ice‐cold water and the product was separated out, filtered,
washed with cold water. The product was purified by
recrystallization from ethanol to give 2‐bromo‐indandione 2,
yield 86%, m.p. 98–101°C.
O
(2)
O
(1)
O
S
N
R
N
N
N
H
(7)
O
O
O
S
N
H
N
Ar
H
(6)
N
3‐(Substituted)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo
[3.3.0]‐1(5),3‐octadiene, 3a–f. An equimolar mixture of compound
2 (0.01 mol) and substituted thiocarbamide (0.01 mol) in ethanol
(20 mL) was refluxed in presence of DMF (0.02 mol) for about
4–5 h. The progress of reaction was monitored on TLC. Upon
completion of reaction, the reaction mixture was quenched into
crushed ice. The product precipitated out was filtered, washed
with water, and purified by recrystallization from ethanol to give
thiazoles 3a–f.
(3)
O
Br
OH
(2)
O
O
S
O
3‐Imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐
octadiene (3a). M.p. = >260°C, Yield = 88%, IR (cm−1):3158,
N
H
Ar
R
N
H
N
1
1252, H NMR (500 MHz, DMSO‐d6, δ ppm): 4.1 (s, 1H, NH),
(4)
(5)
7.15–8.18 (m, 4H, ArH), 9.79 (s, 1H, NH),13C NMR (500 MHz,
DMSO‐d6, ppm): 115.28, 119.45(C═C), 122.31, 124.23, 125.32,
128.21, 128.23, 131.42, 133.47,135.56,136.10,138.89 (Ar C),
154.25 (C═N), 180.72 (C═O). Calcd for C10H6ON2S: C, 59.41;
H, 2.97; N, 13.86%. Found: C, 59.36; H, 2.91; N, 13.81%.
3‐(Phenyl)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo
[3.3.0]‐1(5),3‐octadiene (3b). M.p. = 245–247°C, Yield = 89%,
Reaction condition : Alcohol/Reflux for 4-5Hrs/DMF
VMP‐1 melting point apparatus and are expressed in degree
celsius. The progress of the reaction was monitored in situ by a
thin layer chromatography (TLC) on silica gel‐coated aluminum
plates as adsorbent and UV light as visualizing agent. IR spectra
in KBr pellets were recorded on Perkin‐Elmer spectrophotometer
in the range of 4000‐400 cm−1. 1H NMR spectra were obtained
1
IR (cm−1): 3148, 1286, H NMR (500 MHz, DMSO‐d6,δppm):
7.18–8.28 (m, 9H, ArH), 9.68 (s, 1H, NH),13C NMR (500 MHz,
DMSO‐d6, ppm): 113.48, 119.24 (C═C), 122.58, 122.72,
124.36, 127.21, 129.56, 131.0, 131.31, 135.36, 136.89, 137.84
(Ar C), 157.23 (C═N), 180.77 (C═O). Calcd for C16H10ON2S:
Table 1
Physical characterization of synthesized compounds.
Compound
Ar/R
Mol. formula
M.p. (°C)
Yields (%)
3a
3b
3c
3d
3e
3f
4a
4b
4c
4d
4e
4f
5a
5b
5c
6
7a
7b
7c
H
C6H5
C
10H6ON2S
>260
245–247
88
89
92
87
89
87
89
82
81
87
86
89
89
84
82
91
81
87
84
C16H10ON2S
C16H9ON2SCl
C17H12O2N2S
C16H9ON2SCl
C17H12ON2S
C10H6O2N2
C16H10O2N2
C16H9O2N2Cl
C17H12O3N2
C16H9O4N3
C17H12O2N2
C15H9NOS
C15H8NOSCl
C16H11NOS
C15H9NO2
C11H6N4OS
C12H8N4OS
C13H10N4OS
4‐Cl–C6H4
4‐OCH3–C6H4
3‐Cl–C6H4
4‐CH3–C6H4
H
220–223
210–213
210–213
228–231
178–180
172–174
164–166
155–159
207–208
180–184
146–148
145–147
120–124
187–189
215–217
201–203
229–231
C6H5
4‐Cl–C6H4
4‐OCH3–C6H4
4‐NO2–C6H4
4‐CH3–C6H4
H
Cl
CH3
H
H
CH3
C2H5
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Dimethylformamide Catalyzed Synthesis of Novel Heterocycles—Their
Characterization and Antimicrobial Evaluation
C, 69.06; H, 3.60; N, 10.07%. Found: C, 69.02; H, 3.52; N,
10.01%.
3‐(4′‐Chlorophenyl)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (4c). M.p.= 164–166°C, Yield
= 81%, IR (cm−1): 3373, 1736, 1H NMR (500 MHz, DMSO‐
d6, δ ppm): 6.78–7.86 (m, 8H, ArH), 9.72 (s, 1H, NH), 13C
NMR (500 MHz, DMSO‐d6, ppm): 113.89, 120.24 (C═C),
123.67, 124.45, 126.63, 127.43, 128.54, 129.87, 130.75,
131.43, 131.87, 132.76 (Ar C), 155.67 (C═N), 183.68 (C═O).
Calcd for C16H9N202Cl: C, 64.76; H, 3.04; N, 9.44%. Found:
C, 64.71; H, 2.94; N, 9.41%.
3‐(4′‐Chlorophenyl)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (3c). M.p. = 220–223°C, Yield
= 92%, IR (cm−1): 3368, 1705, 1H NMR (500 MHz, DMSO‐d6, δ
ppm): 7.18–8.62 (m, 8H, ArH), 9.81 (s, 1H, NH), 13C NMR (500
MHz, DMSO‐d6, ppm): 114.22, 120.73 (C═C), 122.56, 123.41,
124.23, 125.32, 128.94, 130.45, 131.41, 135.32, 136.54, 139.95
(Ar C), 156.34 (C═N), 182.73 (C═O). Calcd for C16H9N20SCl:
C, 61.44; H, 2.88; N, 8.96%. Found: C, 61.34; H, 2.78; N, 9.01%.
3‐(4′‐Methoxyphenyl)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (3d). M.p. = 210–213°C, Yield =
3‐(4′‐Methoxyphenyl)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (4d). M.p. = 155–159°C, Yield =
1
87%, IR (cm−1): 3343, 1698, H NMR (500 MHz, DMSO‐d6, δ
1
87%, IR (cm−1): 3368, 1776, H NMR (500 MHz, DMSO‐d6, δ
ppm): 3.84 (s, 3H, OCH3), 7.26–8.18 (m, 8H, ArH), 9.76 (s, 1H,
NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 56.05 (OCH3),
114.61, 119.86 (C═C), 124.47, 125.48, 126.52, 127.45, 127.98,
129.58, 131.24, 132.45, 133.18, 134.42 (Ar C), 154.68 (C═N),
180.57 (C═O). Calcd for C17H12N203: C, 69.86; H, 4.11; N,
9.59%. Found: C, 69.81; H, 4.02; N, 9.51%.
ppm): 3.91 (s, 3H, OCH3), 7.08–8.32 (m, 8H, ArH), 9.76 (s, 1H,
NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 55.46 (OCH3),
114.20, 120.73 (C═C), 121.71, 122.38, 123.42, 124.56, 125.84,
127.85, 129.65, 131.24, 138.21, 139.96 (Ar C), 154.33 (C═N),
183.74 (C═O). Calcd for C17H12N202S: C, 66.22; H, 3.92; N,
9.08%. Found: C, 66.32; H, 4.02; N, 9.12%.
3‐(4′‐Nitrophenyl)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐
3‐(3′‐Chlorophenyl)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (3e). M.p. = 210–213°C, Yield
= 89%, IR (cm−1): 3368, 1726, 1H NMR (500 MHz, DMSO‐d6, δ
ppm): 6.98–8.08 (m, 8H, ArH), 9.74 (s, 1H, NH), 13C NMR (500
MHz, DMSO‐d6, ppm): 113.87, 119.47 (C═C), 122.37, 124.38,
125.49, 127.35, 128.43, 129.87, 132.38, 135.56, 136.56, 137.89
(Ar C), 158.3 (C═N), 186.7 (C═O). Calcd for C16H9N20SCl: C,
61.44; H, 2.88; N, 8.96%. Found: C, 61.38; H, 2.80; N, 8.89%.
3‐(4′‐Methylphenyl)‐imino‐2‐thia‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (3f). M.p. = 228–231°C, Yield
bicyclo[3.3.0]‐1(5),3‐octadiene (4e). M.p. = 207–208°C,
Yield = 86%, IR (cm−1): 3473, 1756, 1H NMR (500 MHz,
DMSO‐d6, δ ppm): 7.25–8.28 (m, 8H, ArH), 9.69 (s, 1H, NH),
13C NMR (500 MHz, DMSO‐d6, ppm): 114.76, 120.04
(C═C), 121.98, 122.74, 123.45, 123.87, 124.87, 125.47,
126.41, 127.65, 128.15, 129.87 (Ar C), 156.68 (C═N), 182.52
(C═O). Calcd for C16H9N304: C, 62.54; H, 2.93; N, 13.68%.
Found: C, 62.48; H, 2.84, N, 13.61%.
3‐(4′‐Methylphenyl)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐
bicyclo[3.3.0]‐1(5),3‐octadiene (4f). M.p. = 180–184°C, Yield
= 89%, IR (cm−1): 3453, 1756, 1H NMR (500 MHz, DMSO‐
d6, δ ppm): 2.22 (s, 3H, CH3), 7.28–8.14 (m, 8H, ArH), 9.74
(s, 1H, NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 23.91
(CH3), 115.16, 119.48 (C═C), 122.64, 123.84, 124.54, 125.08,
126.84, 127.24, 128.12, 129.51, 130.41, 131.52 (Ar C), 155.69
(C═N), 180.53(C═O). Calcd for C17H12N202: C, 73.90; H,
4.35; N, 10.14%. Found: C, 73.84; H, 4.32; N, 10.19%.
2‐Thia‐5‐aza‐9‐oxo‐3,4‐(substituted)benzo‐7,8‐benzo‐bicyclo
[4.3.0]‐1(6)nonene, 5a–c. An equimolar mixture of compound 2
(0.01 mol) and substituted aminothiophenol (0.01 mol) in
ethanol (20 mL) was refluxed in presence of DMF (0.02 mol)
for about 4–5 h. The progress of reaction was monitored on
TLC. Upon completion of reaction, the reaction mixture was
quenched into crushed ice. The product precipitated out was
filtered, washed with water, and purified by recrystallization
from ethanol to give Thiazines 5a–c.
1
= 87%, IR (cm−1): 3338, 1726, H NMR (500 MHz, DMSO‐d6,
δ ppm): 2.24 (s, 3H, CH3), 6.76–7.85 (m, 8H, ArH), 9.68 (s,
1H, NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 23.35 (CH3),
112.96, 119.87 (C═C), 123.35, 124.36, 125.42, 126.73,
128.57, 130.19, 131.14, 135.36, 136.35, 137.89 (Ar C), 153.43
(C═N), 185.47 (C═O). Calcd for C17H12N202S: C, 69.86; H,
4.11; N, 9.59%. Found: C, 69.82; H, 4.02; N, 9.48%.
3‐(Substituted)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo
[3.3.0]‐1(5),3‐octadiene, 4a–f. A mixture of compound 2 (0.01
mol) and substituted carbamides (0.01 mol) in ethanol (20 mL)
was refluxed in presence of DMF (0.02 mol) for about 4–5 h.
The progress of reaction was monitored on TLC. Upon
completion of reaction, the reaction mixture was quenched into
crushed ice. The product precipitated out was filtered, washed
with water and purified by recrystallization from ethanol to give
oxazoles 4a–f.
3‐Imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐1(5),3‐
octadiene (4a). M.p. = 178–180°C, Yield = 89%, IR (cm−1):
3473, 1766, 1H NMR (500 MHz, DMSO‐d6, δ ppm): 4.28 (s,
1H, NH), 6.98–7.98 (m, 4H, ArH), 9.85 (s, 1H, NH), 13C NMR
(500 MHz, DMSO‐d6, ppm): 115.1, 119.4 (C═C), 122.4, 123.45,
125.47, 126.32, 127.43, 128.59, 130.43, 131.23, 135.52, 131.7
(Ar C), 152.6 (C═N), 179.5(C═O). Calcd for C10H6N202: C,
64.52; H, 3.23; N, 15.05%. Found: C, 64.48; H, 3.17, N, 15.01%.
3‐(Phenyl)‐imino‐2‐oxa‐4‐aza‐6,7‐benzo‐8‐oxo‐bicyclo[3.3.0]‐
1(5),3‐octadiene (4b). M.p. = 172–174°C, Yield = 82%, IR
2‐Thia‐5‐aza‐9‐oxo‐3,4‐benzo‐7,8‐benzo‐bicyclo[4.3.0]‐1(6)
nonene (5a). M.p. = 146–148°C, Yield = 89%, IR (cm−1): 3290,
1760, 1H NMR (500 MHz, DMSO‐d6, δ ppm): 6.87–7.98 (m,
8H, ArH), 9.84 (s, 1H, NH). 13C NMR (500 MHz, DMSO‐d6,
ppm): 118.26, 120.37 (C═C), 121.82, 122.41, 123.21, 123.89,
124.51, 125.41, 126.84, 127.15, 129.85, 130.45, 132.14, 135.68
(Ar C), 179.25 (C═O). Calcd for C15H9N0S: C, 71.71; H, 3.59;
N, 5.58%. Found: C, 71.64; H, 3.48; N, 5.49%.
2‐Thia‐5‐aza‐9‐oxo‐3,4‐(3′‐chloro)benzo‐7,8‐benzo‐bicyclo
[4.3.0]‐1(6) nonene (5b). M.p. = 145–147°C, Yield = 84%, IR
(cm−1): 3360, 1680, 1H NMR (500 MHz, DMSO‐d6, δ ppm):
7.28–8.16 (m, 8H, ArH), 10.42 (s, 1H, NH), 13C NMR (500
MHz, DMSO‐d6, ppm): 118.18, 120.63 (C═C), 123.84,
124.74, 125.21, 126.63, 127.65, 129.74, 130.21, 131.28,
132.56, 133.52, 134.08, 135.74 (Ar C), 182.84 (C═O). Calcd
for C15H8N0SCl: C, 63.05; H, 2.80; N, 4.90%. Found: C,
63.01; H, 2.73; N, 4.78%.
1
(cm−1): 3373, 1696, H NMR (500 MHz, DMSO‐d6, δ ppm):
6.87–7.54 (m, 9H, ArH), 9.68 (s, 1H, NH), 13C NMR (500
MHz, DMSO‐d6, ppm): 114.89, 120.40 (C═C), 121.94,
122.45, 123.57, 124.35, 126.43, 128.53, 130.75, 131.43,
132.31, 135.76 (ArC), 154.66 (C═N), 180.56 (C═O). Calcd
for C16H10N202: C, 73.28; H, 3.81; N, 10.69%. Found: C,
73.20; H, 3.74; N, 10.62%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

V. V. Dabholkar, S. R. Patil, and R. V. Pandey
Vol 000
2‐Thia‐5‐aza‐9‐oxo‐3, 4‐(3′‐methyl) benzo‐7,8‐benzo‐bicyclo
[4.3.0]‐1(6) nonene (5c). M.p. = 120–124°C, Yield = 82%, IR
(cm−1): 3370, 1690, 1H NMR (500 MHz, DMSO‐d6, δ ppm):
2.48 (s, 3H, CH3), 7.28–8.25 (m, 8H, ArH), 10.40 (s, 1H, NH),
13C NMR (500 MHz, DMSO‐d6, ppm): 23.91 (CH3), 118.20,
120.32 (C═C), 121.84, 122.75, 124.46, 125.62, 126.28, 128.54,
129.65, 131.24, 132.45, 133.51, 134.43, 135.62 (ArC), 180.58
(C═O). Calcd for C16H11N0S: C, 72.43; H, 4.18; N, 5.28%.
Found: C, 72.34; H, 4.23; N, 5.19%.
C11H6N40S: C, 54.55; H, 2.48; N, 23.14%. Found: C, 54.46; H,
2.38; N, 23.01%.
3′‐Methyl‐(1′,2′,4′)triazolo [5,6‐b][indeno (2,3‐e)]‐1,3,4‐
thiadiazine (7b). M.p. = 201–203°C, Yield = 87%, IR (cm−1):
1
3153, 1730, H NMR (500 MHz, DMSO‐d6, δ ppm): 2.42 (s, 3H,
CH3), 7.15–8.35 (m, 4H, ArH), 9.74 (s, 1H, NH), 13C NMR (500
MHz, DMSO‐d6, ppm): 23.67 (CH3), 123.54, 125.38 (C═C),
128.79, 129.51, 130.12, 131.08, 131.97, 132.41 (Ar C), 149.54
(C═N), 155.98 (C═N), 167.47(C═O). Calcd for C12H8N40S: C,
56.24; H, 3.15; N, 21.86%. Found: C, 56.34; H, 3.12; N, 21.79%.
3′‐Ethyl‐(1′,2′,4′)triazolo[5,6‐b][indeno (2,3‐e)]‐1,3,4‐
thiadiazine (7c). M.p. = 201–203°C, Yield = 87%, IR (cm−1):
3153, 1730, 1H NMR (500 MHz, DMSO‐d6, δ ppm): 2.42(q, 3H,
CH3), 2.21(t, 2H, CH2), 6.85–7.98 (m, 4H, ArH), 9.68 (s, 1H,
NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 23.67 (CH3), 29.48
(CH2), 124.53, 127.34 (C═C), 127.82, 127.98, 128.73, 129.01,
130.56, 131.98 (Ar C), 150.55 (C═N), 154.85 (C═N), 170.42
(C═O). Calcd for C13H10N40S: C, 57.78; H, 3.70; N, 20.74%.
Found: C, 57.71; H, 3.62; N, 20.68%.
2‐Oxa‐5‐aza‐9‐oxo‐(3,4)‐(7,8)‐dibenzo‐bicyclo[4.3.0]‐1(6)
nonene (6). An equimolar mixture of compound 2 (0.01 mol)
and aminophenol (0.01 mol) in ethanol (20 mL) was refluxed
in presence of DMF (0.02 mol) for about 4–5 h. The progress
of reaction was monitored on TLC. Upon completion of
reaction, the reaction mixture was quenched into crushed ice.
The product precipitated out was filtered, washed with water,
and purified by recrystallization from ethanol to yield 6.
2‐Oxa‐5‐aza‐9‐oxo‐(3,4)‐(7,8)‐dibenzo‐bicyclo[4.3.0]‐1(6)
nonene (6). M.p. = 187–189°C, Yield = 91%, IR (cm−1): 3287,
1
1757, H NMR (500 MHz, DMSO‐d6, δ ppm): 6.87–7.98 (m,
8H, ArH), 9.84 (s, 1H, NH). 13C NMR (500 MHz, DMSO‐d6,
ppm): 118.26, 120.37 (C═C), 121.82, 122.85, 123.41, 124.84,
125.62, 126.84, 127.42, 128.32, 131.64, 133.21, 134.35,
135.68 (Ar C), 179.25 (C═O). Calcd for C15H9N02: C, 76.60;
H, 3.83; N, 5.96%. Found: C, 76.49; H, 3.74, N, 5.87%.
3′‐Substituted‐(1′,2′,4′)triazolo[5,6‐b][indeno (2,3‐e)]‐1,3,4‐
thiadiazine, 7a–c. An equimolar mixture of compound 2 (0.01
mol) and substituted triazole (0.0 mol) in ethanol (20 mL) was
refluxed in presence of DMF (0.02 mol) for about 4–5 h. The
progress of reaction was monitored on TLC. Upon completion of
reaction, the reaction mixture was quenched into crushed ice. The
product precipitated out was filtered, washed with water, and
purified by recrystallization from ethanol to yield 7a–c.
3′‐H‐(1′,2′,4′) triazolo [5,6‐b][indeno (2,3‐e)]‐1,3,4‐thiadiazine
(7a). M.p. = 215–217°C, Yield = 81%, IR (cm−1): 3353, 1730, 1H
NMR (500 MHz, DMSO‐d6, δ ppm): 7.09–8.54 (m, 5H, ArH, CH),
9.84 (s, 1H, NH), 13C NMR (500 MHz, DMSO‐d6, ppm): 122.15,
124.36 (C═C), 126.84, 127.45, 128.14, 130.53, 131.14, 132.92
(Ar C), 148.54 (C═N), 156.56 (C═N), 168.48 (C═O). Calcd for
ANTIMICROBIAL EVALUATION
The newly synthesized compounds were tested for their
antimicrobial activity against the following microorganisms:
(a) Gram‐negative: Escherichia coli, Pseudomonas putide;
(b) Gram‐positive: Bacillus subtilis, Streptococcus lactis;
(c) Fungi: Aspergillus niger, Penicillium sp.; (d) Yeast:
Candida albicans. The preliminary screening of the investi-
gated compounds was performed using the filter paper disk‐
diffusion method [14]. The compounds were tested at a
concentration of 100 μg/mL. The zone of inhibition was
measured in millimeter and compared with reference
standard ampicillin trihydrate (100 μg/mL). The compounds
tested displayed good activity toward Gram positive
bacteria, but were less active against Gram‐negative bacteria.
The results of antibacterial screening studies are reported in
Table 2.
Table 2
Antimicrobial activities of some newly synthesized compounds.
Inhibition zone (mm)
Gram negative
Gram positive
Fungi
Yeast
Compound
3d
4f
5a
E. coli
P. putide
B. subtilis
S. lactis
A. niger
P. sp.
C. albicans
17
16
15
18
13
24
15
16
14
19
18
20
18
17
18
19
17
19
21
21
19
20
20
22
12
10
8
8
0
10
10
8
8
0
5
5
5
5
0
5c
7b
Ampicilin®
24
14
14
E. coli, Escherichia coli; P. putide, Pseudomonas putide; B. subtilis, Bacillus subtilis; S. lactis, Sterptococcus lactis; A. niger, Aspergillus niger; P. sp.,
Penicillium sp.; C. albicans, Candida Albicans.
The sensitivity of microorganisms to the tested compounds is identified in the following manner:
Highly sensitive = inhibition zone: 15–20 mm.
Moderately sensitive = inhibition zone: 10–15 mm.
Slightly sensitive = inhibition zone: 5–10 mm.
Not sensitive = inhibition zone: 0 mm.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
Dimethylformamide Catalyzed Synthesis of Novel Heterocycles—Their
Characterization and Antimicrobial Evaluation
[4] Wolff, M. E. Burger’s Medicinal Chemistry; Wiley: New
York, 1997; Vol. 4, 889.
[5] Pandey, V. K.; Saxena, S. K.; Bajpai, S. K. Indian J Chem
2004, 43B, 1015.
[6] Bhatt, A. K.; Karadia, H. G.; Shah, P. R.; Parmar, M. P.; Patel,
H. D. Indian J Heterocyclic Chem 2004, 13, 281.
[7] Richardson, K. Curr Med Res Opin 1991, 12SI, 60.
[8] Gupta, R.; Gupta, A. K.; Paul, S. Indian J Chem 1998,
37B, 1211.
Acknowledgments. The authors are grateful to the Principal Ms.
Manju J. Nichani and Management of K.C. College, Mumbai, for
providing necessary facilities. Authors are also thankful to the
Director, Institute of Science, Mumbai, for providing spectral
analyses.
REFERENCES AND NOTES
[9] Sadhu, B. P.; Gupta, K. Geobios 1997, 24, 181.
[10] Joshua, C. P. J Org Chem 1963, 28, 1293.
[11] Rabjohn, N. Org Synth Coll 963, 4, 52.
[12] Brewster, R. Q.; Dains, F. B. J Am Chem Soc 1936, 58, 1364.
[13] Mittal, R. L.; Jain, S. J Chem Soc (C), 1969, 16, 2148.
[14] Arthington‐Skaggs, B. A.,Morrison, C. J Microbiol 2000,
38, 2254.
[1] Kalluraya, B.; Isloor, B.; Frank, P. V.; Jagadeesha, R. L. Indian J
Heterocyclic Chem 2004, 13, 245.
[2] Metzer J. V. Comprehensive Heterocyclic Chemistry; Katritzky,
A. R., Rees, C. W., Eds.; Pergamon Press: Oxford, 1984; Vol.5, p328.
[3] Lambardino, J.; Wiseman, E.; Josephine, C. J Med Chem
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet