Synthesis of thiazinobenzimidazole derivatives in a solventless system under microwave irradiation

Article abstract of DOI:10.1080/10426500590885011

A series of thiazino [3,2-a] benzimidazole derivatives were synthesized in a solventless system under microwave irradiation in a very short time and in excellent yields. Copyright Taylor & Francis Inc.

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Phosphorus, Sulfur, and Silicon
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Synthesis of
Thiazinobenzimidazole
Derivatives in a Solventless
System Under Microwave
Irradiation
a
a
Majid M. Heravi , Navabeh Nami , Hossien A.
a
a
Oskooie & Rahim Hekmatshoar
a
Department of Chemistry, School of Sciences,
Azzahra University , Vanak, Tehran, Iran
Published online: 01 Feb 2007.
To cite this article: Majid M. Heravi , Navabeh Nami , Hossien A. Oskooie & Rahim
Hekmatshoar (2005) Synthesis of Thiazinobenzimidazole Derivatives in a Solventless
System Under Microwave Irradiation, Phosphorus, Sulfur, and Silicon and the Related
Elements, 180:7, 1605-1610, DOI: 10.1080/10426500590885011
To link to this article: http://dx.doi.org/10.1080/10426500590885011
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Phosphorus, Sulfur, and Silicon, 180:1605–1610, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590885011
Synthesis of Thiazinobenzimidazole Derivatives in a
Solventless System Under Microwave Irradiation
Majid M. Heravi
Navabeh Nami
Hossien A. Oskooie
Rahim Hekmatshoar
Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
A series of thiazino [3,2-a] benzimidazole derivatives were synthesized in a sol-
ventless system under microwave irradiation in a very short time and in excellent
yields.
Keywords Benzimidazole; microwave irradiation; solventless system; thiazinobenzim-
idazole
1
,2
Benzimidazole derivatives exhibit antibacterial activity, act as hypo-
3
glycaemic agents, and more over are indicated as being associated with
4
a particularly wide range of biological properti e` s, including antitumor,
5
antiviral, and antitubercular activity. These compounds are an im-
portant class of nitrogen- and sulfur-containing heterocycles and they
6
constitute useful intermediates in organic synthesis.
7
The microwave-enhanced chemical reactions have gained popular-
ity over the usual homogeneous and heterogeneous reactions as they
can be conducted rapidly and pure products are obtained in high yields
in a solvent-free condition. Organic solvents are not only expensive,
they are also hazardous and flammable.8
We are interested in the chemistry of heterocyclic compounds
9
containing nitrogen and sulfur atoms. We are also interested in
microwave-assisted organic reactions in a solventless system.10 As part
of a research program on the synthesis of a heterocyclic system con-
taining nitrogen and sulfur in a solventless system under microwave
irradiation and with a view to extending the synthetic utility of dialkyl
Received July 15, 2004; accepted August 10, 2004.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Sci-
ences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
1605

1
606
M. M. Heravi et al.
acetylendicarboxylate,11 we have investigated the addition of the latter
to 2-mercapto benzimidazole under microwave irradiation in a solvent-
less system.
In 1978, McKillop and his co-workers12 reported that benzimidazole-
2-thione 1 reacted with DMAD in either methanol or acetic acid to give
mixtures of two 1:1 molar-MeOH adducts. One adduct was identified
as 2a by X-ray crystallography but the other adduct, which was not
isolated, was tentatively assigned structures 3a.
In 1981, Acheson et al.13 have found that thione 1 and DMAD reacted
in wet and dry acetonitrile to give only 2a and in dry methanol to give
only 3a.
We have investigated the addition of DMAD or DEAD to 2-mercapto
benzimidazole under microwave irradiation in solventless system.
The reactions were simply conducted by mixing of 1 with dialkyl
acetylenedicarboxylat (R = Me or Et) in a beaker and placing the beaker
in a microwave oven for a short period of time. The progress of the
reaction was monitored by TLC using ethanol and ethyl acetate as an
eluent. Our product showed the same physical and spectroscopic data
as given for 3a in the literature13 (Scheme 1). We also used diethyl
acetylene dicarboxylate to obtain the different substituted methyl-2-
oxo-2H-thiazino[3, 2-a] benzimidazole-4-carboxylate. 3b.13
SCHEME 1
Reaction of 5-methoxy benzimidazole-2-thione 4 with DMAD in ei-
ther hot methanol or a solventless condition under microwave irradi-
ation gave a mixture of two isomers that showed closely moving spots
in TLC (ethanol: ethyl acetate) which could be separated chromato-
graphically. These compounds were identified as methyl-7-methoxy-
2-oxo-2H-thiazino[3, 2-a]benzimidazole-4-carboxylate, 5a, and methyl-
8-methoxy-2-oxo-2H-thiazino[3, 2-a]benzimidazole-4-carboxylate, 6a
(
Scheme 2).
In 1H-NMR spectra of 5a, 9-H (7.58 δ) is more shielded than 6-H of
a (8.32 δ, near to C O).
6

Thiazinobenzimidazoles
1607
SCHEME 2
EXPERIMENTAL
The melting points were obtained using an Electrothermal IA 9100 Dig-
ital Melting Point apparatus. The IR spectra were recorded on a 4300
1
Shimadzu spectrometer. HNMR spectra were recorded on a 500 MHz
spectrometer using TMS as internal standard.
SYNTHESIS OF THIAZINO[3,2-a]BENZIMIDAZOLE
General Procedure
Compound 1 and 4 (1 mol) was mixed with DMAD or DEAD (1 mol)
thoroughly in a beaker; the beaker was placed in a microwave oven for
5
min. The progress of reaction was monitored by TLC using ethanol:
ethyl acetate (3:1) as an eluent. The mixture of two isomers was sepa-
rated chromatographically (ethanol: ethyl acetate 3:1). 3a, 3b, 5a, 5b,
6
a, and 6b were crystallized from a suitable solvent. The selected phys-
ical and spectroscopic data are given below.
METHYL-2-OXO-2H-THIAZINO[3,2-a]BENZIMIDAZOLE-4-
CARBOXYLATE 3a
◦
13
◦
Mp = 172 C yellow micro needles from MeOH, (Lit 172.5–173 C) yield
1
9
0%. H-NMR (CDCl3)δ 4.05 (s, 3H, OMe), 7.45 (m, 1H, benzen hydro-
gen), 7.52 (s, 1H, CH), 7.55 (m, 1H, benzene hydrogen), 7.81 (d, J =
.8, 1H, benzenhydrogen), 8.58 (d, J = 7.9, 1H, benzen hydrogen, near
of CO). IR (KBr): 3035, 2910, 1731, 1691, 1580, 1470, 1430, 1354, 1256,
7
−1
+
1
1
184, 1108, and 755 cm . MS, m/z; M , 260 (100), 201 (25), 174 (21),
29 (15), 90 (7.2), 77 (4), 63 (5), 39 (4).

1
608
M. M. Heravi et al.
ETHYL-2-OXO-2H-THIAZINO[3,2-a]BENZIMIDAZOLE-4-
CARBOXYLATE 3b
◦
13
◦
Mp = 135 C, yellow micro needles from EtOH, (Lit .135–137 C) yield
1
8
7%. H-NMR (CDCl3)δ 1.45 (t, J = 7.1, 3H, Me), 4.50 (q, J = 7.1, 2H,
CH2), 7.46 (m, 2H, benzen hydrogen), 7.49 (s, 1H, = CH), 7.82 (d, J
5.3, 1H, benzene hydrogen), 8.59 (d, J = 5, 1H, benzene hydrogen).
IR (KBr): 3060, 2976, 2361, 1726, 1689, 1586, 1521, 1477, 1438, 1363,
=
−1
1
298, 1251, 1186, 1101, 1033, 977, 756 cm .
METHYL-7-METHOXY-2-OXO-2H-THIAZINO[3,2-a]-
BENZIMIDAZOLE-4-CARBOXYLATE 5a
◦
1
Mp = 223 C, Orange micro needles, from MeOH yield 44%. H-NMR
(
CDCl3)δ 3.87 (s, 3H, OMe), 4.01 (s, 3H, OMe), 7.05 (d, J = 8.6, 1H,
benzene hydrogen), 7.38 (s, 1H, CH), 7.58 (d, J = 8.6, 1H, benzene
hydrogen), 7.98 (s, 1H, benzene hydrogen). IR (KBr): 3060, 2923, 2853,
1
733, 1691, 1617, 1477, 1433, 1366, 1292, 1249, 1194, 1148, 1114, 1020,
−
1
+
923, 760 cm . MS, m/z; M , 290 (100), 275 (57), 247 (7), 207 (35), 159
(
11), 44 (17), 28 (92).
ETHYL-7-METHOXY-2-OXO-2H-THIAZINO[3,2-a]-
BENZIMIDAZOLE-4-CARBOXYLATE 5b
◦
1
Mp = 126 C, Orange powder from EtOH, yield 35%. H-NMR (CDCl3)δ
1
.38 (t, J = 8.5, 3H, Me), 3.88 (s, 3H, OMe), 4.37 (q, J = 8.5, 2H, OCH2),
.89 (d.d, J = 8.6, 1.6, 1H, benzene hydrogen), 7.16 (d, J = 1.6, 1H,
6
benzene hydrogen), 7.18 (s, 1H, CH), 7.80 (d, J = 8.6, 1H, benzene
hydrogen). IR (KBr): 3030, 1729, 1682, 1609, 1578, 1501, 1428, 1384,
−1
+
1
312, 1195, 1145, 1024 cm . MS, m/z; M, 304 (100), 298 (13), 276 (34),
61 (43.75), 203 (7), 189 (13), 159 (13), 85 (8), 69 (5), 53 (6), 32 (4).
2
METHYL-8-METHOXY-2-OXO-2H-THIAZINO[3,2-a]-
BENZIMIDAZOLE-4-CARBOXYLATE 6a
◦
1
Mp = 140 C, orange micro needles from MeOH, yield 56%. H-NMR
(
CDCl3)δ 3.85 (s, 3H, OMe), 4.01 (s, 3H, OMe), 6.97 (d, J = 8.6, 1H,
benzen hydrogen), 7.16 (s, 1H, benzene hydrogen), 7.42 (s, 1H, CH),
8
1
1
2
.32 (d, 8.6, 1H, benzen hydrogen). IR (KBr): 3098, 3049, 2947, 2828,
729, 1690, 1621, 1517, 1475, 1433, 1386, 1323, 1281, 1196, 1138, 1099,
−1
+
021, 932, 865, 752, 711, 628 cm . MS, m/z; M , 290 (100), 275 (57),
47 (7), 207 (35), 159 (11), 44 (17), 28 (92).

Thiazinobenzimidazoles
1609
ETHYL-8-METHOXY-2-OXO-2H-THIAZINO[3,2-a]-
BENZIMIDAZOLE-4-CARBOXYLATE 6b
◦
1
Mp = 139 C, orange micro needles from EtOH, yield 65%. H-NMR
(
CDCl3)δ 1.45 (t, J = 7.1, 3H, Me), 3.92 (s, 3H, OMe), 4.49 (q, J = 7.1,
2
1
H, CH2)7.07 (d.d, J = 8.9, 2.2, 1H, benzene hydrogen), 7.25 (d, 2.2,
H, benzene hydrogen), 7.5 (s, 1H, CH), 8.43 (d, J = 8.9, 1H, benzene
hydrogen). IR (KBr): 3035, 2960, 1697, 1690, 1576, 1463, 1424, 1362,
−1
+
1
291, 1242, 1193, 1145 cm . MS, m/z; M, 304 (100), 290 (19), 261 (25),
41 (8), 224 (35), 209 (22), 189 (12), 159 (23), 94 (5), 77 (8), 43 (9).
2
CAUTION
Although we did not have any accident, the use of a microwave oven in
an efficient hood is highly recommended.
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