Synthesis of benzimidazole thiazolinone derivatives under microwave irradiation

Article abstract of DOI:10.3184/174751911X13203357106346

Organic compounds containing the thiazolinone ring are of increasing interest due to their bactericidal, pesticidal, anticonvulsant, antiinflammatory, antithyroidal and antimicrobial activities. A rapid microwave-assisted synthesis thiazolinone derivatives is described. The 3-(1H-benzo[d]imidazol-2-yl)-2-substituted phenyl thiazolidin-4-one were identified by IR, 1H NMR, elemental analyses. The target compounds were performed in a shorter reaction time compared to conventional heating methods.

Full text of DOI:10.3184/174751911X13203357106346

672 RESEARCH PAPER
NOVEMBER, 672–673
JOURNAL OF CHEMICAL RESEARCH 2011
Synthesis of benzimidazole thiazolinone derivatives under microwave
irradiation
Jun Hu, Peng Yu, Taoyu Zhou and Yanhua Xu*
College of Environment, Nanjing University ofTechnology/ Jiangsu Key Laboratory of Industrial Water-Conservation & Emission Reduction,
Nanjing 210009, P. R. China
Organic compounds containing the thiazolinone ring are of increasing interest due to their bactericidal, pesticidal,
anticonvulsant, antiinflammatory, antithyroidal and antimicrobial activities. A rapid microwave-assisted synthesis
thiazolinone derivatives is described. The 3-(1H-benzo[d]imidazol-2-yl)-2-substituted phenyl thiazolidin-4-one were
identified by IR, 1H NMR, elemental analyses. The target compounds were performed in a shorter reaction time com-
pared to conventional heating methods.
Keywords: benzimidazole, thiazolinone, microwave irradiation
The derivatives of benzimidazole exhibit diverse biological
properties, such as antiproliferative1, antiparasitic2, antiviral3,
antimicrobial activities.4,5 Organic compounds containing the
thiazolinone ring are of increasing interest due to their known
biological activities that include bactericidal, pesticidal, anti-
convulsant, antiinflammatory, antithyroidal and antimicrobial
activities.6,7
Consequently, the synthesis of compounds containing both
benzimidazole and thiazolinone groups has been intensely
investigated.8–10 However, these derivatives were synthesised
by conventional heating, and the yields were not satisfactory.
We now report the synthesis of a series of new compounds
containing benzimidazole and thiazolinone rings using
microwave irradiation.11,12
irradiation and by conventional heating method. The results
are reported in Table 1.
The 3-(1H-benzo[d]imidazol-2-yl)-2-substituted phenyl
thiazolidin-4-one was synthesised with the previous conven-
tional heating merthods over a long reaction time (12h). The
yields were not satisfactory despite the long reaction time. We
have developed a fast (30 min), convenient, and efficient
method for the preparation of the derivatives under microwave
irradiation. The ease of this method and workup, high yields,
and very short reaction time make this procedure useful and
attractive compared with the currently available methods.
Experimental
Melting points were recorded on an X-4 binocular microscope melt-
1
ing point apparatus. H NMR spectra were recorded on an Avance
Results and discussion
Bruker-500 instrument and chemical shifts in ppm are reported with
TMS as the internal standard. IR spectra in KBr were recorded by a
Perkin-Elmer PE-683 IR spectrometer. Elemental analyses were per-
formed on an Elementer Vario EL III elementary analysis instrument.
MW experiments were carried out on a WF-4000M microwave fast
reaction system (Shanghai Qiyao Analysis Instrument Co., Shanghai,
China).
The 2-Aminobenzimidazole was prepared from o-phenylene-
diamine and cyanamide. The N-(substituted benzylidene)-
1H-benzo[d]imidazol-2-amines (3a–e) were prepared by the
reaction of 2-aminobenzimidazole and substituted benzalde-
hyde under microwave irradiation, and the 3-(1H-benzo[d]
imidazol-2-yl)-2-substituted phenylthiazolidin-4-ones (4a–e)
were then synthesised from N-(substituted benzylidene)-1H-
benzo[d] imidazol-2-amine and thioglycollic acid in toluene
under microwave irradiation as shown in Scheme 1. We syn-
thesised and compared the derivatives both under microwave
Preparation of 2; general procedure
A mixture of o-phenylenediamine 1 (0.01 mol) and hydrochloric acid
was stirred and heated at 100 °C. Cyanamide (0.01 mol) was added
dropwise into the reaction mixture. After the reaction was finished,
Scheme 1 The synthetic route of compounds 4a–e.
* Correspondent. E-mail: yhxu2008@163.com

JOURNAL OF CHEMICAL RESEARCH 2011 673
Table 1 Synthesis of compounds 4a–e
δ: 4.04, 4.13 (d, 2H, CH2), 6.83 (s, 1H, CH), 7.05–7.55 (m, 8H, Hring),
12.47 (s, 1H, NHbenzimidazole); IR(KBr)υ: 3063, 2918, 1684, 1536, 1470,
1111 cm−1; Anal. Calcd for C16H12ClN3OS: C, 58.27; H, 3.67; N,
12.74. Found: C, 58.18; H, 3.46; N, 12.51%.
Entry R
Mode of Time
activation
Power/
Yield
temperature /%
3-(1H-benzo[d]imidazol-2-yl)-2-(4-fluorophenyl)thiazolidin-4-one
(4b): Yield, 79%; m.p. 191–192 °C; 1H NMR (DMSO-d6, 500MHz)
δ: 3.96, 4.23 (d, 2H, CH2), 6.77 (s, 1H, CH), 7.07–7.52 (m, 8H, Hring),
12.41 (s, 1H, NHbenzimidazole); IR(KBr)υ: 3063, 2914, 1705, 1535, 1485,
1222 cm−1; Anal. Calcd for C16H12FN3OS: C, 61.33; H, 3.86; N, 13.41.
Found: C, 62.08; H, 3.46; N, 13.01%.
3-(1H-benzo[d]imidazol-2-yl)-2-(4-nitrophenyl)thiazolidin-4-one
(4c):Yield, 85%; m.p. 225–226 °C; 1H NMR (DMSO-d6, 300MHz) δ:
4.01, 4.23 (d, 2H, CH2), 6.90 (s, 1H, CH), 7.09–8.19 (m, 8H, Hring),
12.41 (s, 1H, NHbenzimidazole); IR(KBr)υ: 3077, 2927, 1710, 1604, 1534,
1486 cm−1; Anal. Calcd for C16H12N4O3S: C, 56.46; H, 3.55; N, 16.46.
Found: C, 56.28; H, 3.46; N, 16.01%.
4a
4b
4c
4d
4e
4a
4b
4c
4d
4e
2-Chloro
MW
MW
MW
MW
MW
CH
30 min
30 min
30 min
30 min
30 min
12h
400 W
400 W
400 W
400 W
400 W
110 °C
110 °C
110 °C
110 °C
110 °C
82%
79%
85%
82%
81%
54%
51%
60%
56%
58%
4-Fluoro
4-Nitro
4-Methyl
4-Trifluoromethyl
2-Chloro
4-Fluoro
CH
12h
4-Nitro
CH
12h
4-Methyl
CH
12h
4-Trifluoromethyl
CH
12h
MW, microware irradiation; CH, conventional heating.
3-(1H-benzo[d]imidazol-2-yl)-2-p-tolylthiazolidin-4-one (4d):Yield,
82%; m.p. 255–256 °C; 1H NMR (DMSO-d6, 300MHz) δ: 2.31
(t, 3H, CH3), 3.91, 4.14 (d, 2H, CH2), 6.73 (s, 1H, CH), 7.08–7.45 (m,
8H, Hring), 12.25 (s, 1H, NHbenzimidazole); IR(KBr)υ: 3051, 2919, 1703,
1536, 1484 cm−1; Anal. Calcd for C17H15N3OS: C, 66.00; H, 4.89; N,
13.58. Found: C, 66.08; H, 4.56; N, 13.41%.
3-(1H-benzo[d]imidazol-2-yl)-2-(4-(trifluoromethyl)phenyl)thiazol
idin-4-one (4e): (81%): m.p. 247–248 °C; 1H NMR (DMSO-d6,
300MHz) δ: 3.97, 4.22 (d, 2H, CH2), 6.87 (s, 1H, CH), 7.07–7.71 (m,
8H, Hring), 12.44 (s, 1H, NHbenzimidazole); IR(KBr)υ: 3054, 2910, 1709,
1537, 1488, 1226 cm−1; Anal. Calcd for C17H12F3N3OS: C, 56.19; H,
3.33; N, 11.56. found: C, 56.28; H, 3.39; N, 11.51%.
50% NaOH (10 mL) was added. After cooling and filtering, crude
compound 2 was obtained. The pure compound 2 was obtained by
recrystallisation from ethanol.
Preparation of 3; general procedure
A mixture of compound 2 (0.01 mol), substituted benzaldehyde
(0.015 mol) and a small amount of piperidine in toluene was stirred
and irradiated in WF-4000M microwave fast reaction system under
400W for 12 min at 110 °C. After cooling and filtering, crude
compound 3 was obtained. The pure compounds were obtained by
recrystallisation from ethanol.
Preparation of 4; general procedure
The generous financial support of this work came from
the National High Technology Research and Development
(863 Program) of China (No. 2007AA06A402), Key Projects
in the National Science and Technology Pillar Program
(No. 2006BAC02A15), Key Projects in the National Water
pollution control and management Pillar Program (No.
2008ZX07101-003), 2011 Key projects of Natural Science of
Jiangsu Province-owned colleges (NO.11KJA610001).
A mixture of compound 3 (0.005 mol) and toluene (50 mL) was
treated with thioglycollic acid (0.005 mol) dropwise and irradiated
in an experimental MW instrument at 400W for 30 min (max. temp.
110 °C). After completion of the reaction, the remaining toluene
was evaporated under reduced pressure. After cooling, the crude
product precipitated. It was filtered, washed with ethanol, dried, and
recrystallised from ethanol to afford the target compound.
N-(2-chlorobenzylidene)-1H-benzo[d]imidazol-2-amine (3a): Yield,
1
83%; m.p. 222–223 °C; H NMR (DMSO-d6, 400 MHz) δ: 12.80
(s, 1H, NHbenzimidazole), 9.79 (s, 1H, Harom), 7.20-8.28 (m, 8H, Hring);
IR(KBr)υ: 3056 (ArH), 1634 (C=N, ring), 1563 (C=N, imine), 1461
(C–N) cm−1; Anal. Calcd for C14H10ClN3: C, 65.76; H, 3.94; N, 16.43.
Found: C, 65.02; H, 4.04; N, 16.17%.
Received 26 October 2011; accepted 1 November 2011
Paper 1100955 doi: 10.3184/174751911X13203357106346
Published online: 22 November 2011
N-(4-fluorobenzylidene)-1H-benzo[d]imidazol-2-amine (3b): Yield,
1
82%; m.p. 185–186 °C; H NMR (DMSO-d6, 300 MHz) δ: 12.65
References
(s, 1H, NHbenzimidazole), 9.46 (s, 1H, Harom), 7.07–8.17 (m, 7H, Hring);
IR (KBr)υ: 3065 (ArH), 1615 (C=N, ring), 1587 (C=N, imine), 1461
(C–N) cm−1; Anal. Calcd for C14H10FN3: C, 70.28; H, 4.21; N, 17.56.
Found: C, 70.22; H, 4.25; N, 17.51%.
1
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N-(4-nitrobenzylidene)-1H-benzo[d]imidazol-2-amine (3c): Yield,
1
90%; m.p. 285–286 °C; H NMR (DMSO-d6, 400 MHz) δ: 12.85
3
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(s, 1H, NHbenzimidazole), 9.60 (s, 1H, Harom), 7.19–8.42 (m, 8H, Hring);
IR(KBr)υ: 3122 (ArH), 1613 (C=N, ring), 1590 (C=N, imine), 1425
(C–N) cm−1; Anal. Calcd for C14H10N4O2: C, 63.15; H, 3.79; N, 21.04.
Found: C, 63.18; H, 3.25; N, 21.08%.
4
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N-(4-methylbenzylidene)-1H-benzo[d]imidazol-2-amine (3d): Yield,
1
85%; m.p. 238–239 °C; H NMR (DMSO-d6, 300 MHz) δ: 12.65
(s, 1H, NHbenzimidazole), 9.40 (s, 1H, Harom), 7.07–7.97 (m, 8H, Hring), 2.42
(s, 3H, CH3); IR(KBr)υ: 3054 (ArH), 1666 (C=N, ring), 1566 (C=N,
imine), 1440 (C–N) cm−1; Anal. Calcd for C15H13N3: C, 76.57; H, 5.57;
N, 17.86. Found: C, 76.51; H, 5.60; N, 17.82%.
N-(4-(trifluoromethyl)benzylidene)-1H-benzo[d]imidazol-2-amine
(3e):Yield, 79%; m.p. 232–234 °C; 1H NMR (DMSO-d6, 300MHz) δ:
12.80 (s, 1H, NHbenzimidazole), 9.56 (s, 1H, Harom), 7.09–8.29 (m, 8H,
Hring); IR(KBr)υ: 3067 (ArH), 1611 (C=N, ring), 1576 (C=N, imine),
1429 (C–N) cm−1; Anal. Calcd for C15H10F3N3: C, 62.28; H, 3.48; N,
14.53. Found: C, 62.33; H, 3.51; N, 14.60%.
9
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3-(1H-benzo[d]imidazol-2-yl)-2-(2-chlorophenyl)thiazolidin-4-one
(4a): Yield, 82%; m.p. 219–220 °C; 1H NMR (DMSO-d6, 300 MHz)

674 JOURNAL OF CHEMICAL RESEARCH 2011
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