An ionic liquid mediated one-pot synthesis of substituted thiazolidinones and benzimidazoles

Article abstract of DOI:10.1016/j.tetlet.2009.06.091

An expeditious one-pot synthesis of 2,3-diaryl/2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones and 1-aryl-1H,3H-thiazolo[3,4-a]benzimidazoles have been accomplished by condensing hetero/aromatic amine, 2-mercaptoacetic acid, aromatic aldehyde and 1,2-phenylenediamine, 2-mercaptoacetic acid and aromatic aldehyde, respectively, in ionic liquids, viz, 1-butyl-3-methyl-imidazolium tetrafluoroborate and 1-methoxyethyl-3-methylimidazolium trifluoroacetate.

Full text of DOI:10.1016/j.tetlet.2009.06.091

Tetrahedron Letters 50 (2009) 5031–5034
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Tetrahedron Letters
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An ionic liquid mediated one-pot synthesis of substituted thiazolidinones
and benzimidazoles
*
Ashok K. Yadav , Manoj Kumar, Tripti Yadav, Renuka Jain
Department of Chemistry, University of Rajasthan, Jaipur 302055, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An expeditious one-pot synthesis of 2,3-diaryl/2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones and 1-aryl-
1H,3H-thiazolo[3,4-a]benzimidazoles have been accomplished by condensing hetero/aromatic amine,
2-mercaptoacetic acid, aromatic aldehyde and 1,2-phenylenediamine, 2-mercaptoacetic acid and aro-
matic aldehyde, respectively, in ionic liquids, viz, 1-butyl-3-methyl-imidazolium tetrafluoroborate and
1-methoxyethyl-3-methylimidazolium trifluoroacetate.
Received 27 March 2009
Revised 15 June 2009
Accepted 18 June 2009
Available online 21 June 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Ionic liquid promoted synthesis
1,3-Thiazolidin-4-ones, 1H,3H-thiazolo[3,4-
a]benzimidazoles
2-Mercaptoacetic acid and aromatic
aldehyde
The molecular modelling and structural activity relationship
investigations1–4, on the development of new non-nucleoside re-
verse transcriptase inhibitors suggest that 2,3-diaryl-1,3-thiazoli-
din-4-ones, 1 and 1H, 3H-thiazolo[3,4-a]benzimidazoles, 2 are
important class of heterocycles, as potential HIV-1RT inhibitors.
Benzimidazoles have been reported to possess important phar-
macological activities such as anti-microbial,5 anti-fungal,6 anti-
parkinson,7 anti-cancer,8 and anti-biotic,9. These derivatives have
also been intelligently exploited as ligands for the asymmetric
transformations.10 The usual methods for their synthesis involve
condensation of carboxylic acids,11 orthoesters,12 amides,13 ni-
triles,14 aldehydes15 and esters with amino aromatics. The synthe-
sis of benzoxazoles, benzthiazoles and benzimidazoles have also
been carried out by condensation of substituted aromatic amines
and aromatic carboxylic acid in 1-butyl-3-methylimidazolium tet-
rafluoroborate.16 A microwave assisted synthesis of compounds 1
and 2 have been reported in toluene as solvent.17 Except ionic li-
quid promoted synthesis described above, most of the synthetic
procedures are associated with harsh reaction conditions, poor
yields and environmentally black-listed solvents. In view of the
diversified applications described above, we hereby report the first
effective one-pot three component synthesis of thiazolidinones
and benzimidazoles. The syntheses were performed in ecologically
friendly conditions with the use of ionic liquids18 and afforded the
desired products in high yield.
The one-pot regioselective synthesis of compounds 1a–i and
2a–e have been performed by taking heteroaromatic amine/1,2-
phenylenediamine with 2-mercaptoacetic acid and an aromatic
aldehyde in ionic liquids, viz 1-butyl-3-methylimidazolium tetra-
fluroborate [BMIM]BF4 and 1-methoxyethyl-3-methylimidazolium
trifluoroacetate [MOEMIM]TFA. The reaction has been carried out
by stirring the reaction mixture under nitrogen atmosphere at
80 2 °C.
The formation of compounds 1a–i19 may be explained as fol-
lows (Scheme 1). The yield of products 1a–i has been presented
in Table 1.
The observation of these data suggests that the electron releas-
ing group at hetero/aromatic amine and electron withdrawing
group on ketone favours the reaction. All these compounds were
characterized unambiguously by IR, 1H NMR, 13C NMR and elemen-
tal analyses.20
Similarly, we have carried out the synthesisof compounds 2a–e21
starting from 1,2-phenylenediamines as shown below (Scheme 2).
The yield of the products is presented in Table 2.
These products 2a–e were characterized by IR, 1H NMR, 13C
NMR and elemental analyses.22
The data presented in Table 2 suggest that the electron releas-
ing substituents on 1,2-phenylenediamine favours the formation
of compound 2a–e.
The observation of yields of compounds 1a–i and 2a–e (Table 1
and Table 2) reveal that [MOEMIM]TFA is a better reaction media
in comparison to [BMIM]BF4. This may be attributed due to the
ability of [MOEMIM]TFA to hydrogen bond with aromatic/hetero-
cyclic/1,2-phenylenediamine.
* Corresponding author. Tel.: +91 141 2552609.
E-mail address: drakyada@yahoo.co.in (A.K. Yadav).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.091

5032
A. K. Yadav et al. / Tetrahedron Letters 50 (2009) 5031–5034
R4
R2
R3
HO
X
SH
+
+
H
R1
NH2
O
Y
O
R5
IL
R2
R2
R3
R4
X
R3
R4
X
R1
N
H
Y
HO
NH
R1
Y
S
O
S
R5
O
R5
1a-i
Scheme 1.
Table 1
Yield of the compounds 1a–i
We have studied the recyclability of the regenerated ionic liq-
uids19 for the products 1e and 2e. The yields of the product in
two cycles are presented in Table 3.
Product
X
Y
R1
R2
R3
R4
R5
Yielda (%)/time (min)
[BMIM]BF4
[MOEMIM]TFA
From Table 3, it is clear that the yield of the products 1e and 2e
decrease in various cycles, yet the IL can be reused with significant
success. Hence, this procedure is advantageous over conventional
reaction media.
In conclusion, an one-pot regioselective synthesis of com-
pounds 1 and 2 has been developed at 80 2 °C in ionic liquid, as
reaction medium and promoter. The absence of catalyst and recy-
clability of IL, make this procedure, cleaner and promising for scale
up.
1a
1b
1c
1d
1e
1f
1g
1h
1i
C
C
C
C
C
N
N
N
N
C
C
C
C
C
C
C
N
N
H
H
H
H
H
H
H
H
H
H
H
Cl
H
F
F
F
Cl
Cl
H
H
H
H
H
H
H
Me
H
Cl
Cl
Cl
F
F
F
F
F
Cl
73/100
78/100
82/100
80/90
80/90
86/90
90/90
85/80
92/80
80/90
85/90
86/80
90/90
Me
Me
OMe
OMe
Cl
Br
Me
Me
88/90
75/100
78/100
81/90
Me
82/100
a
Isolated yield after purification.
R3
NH2
HO
R1R2
+
SH
+
H
NH2
O
R4
O
R4
R4
R3
R3
S
HO
S
N
N
H
N
R1R2
R1R2
N
2a-e
Scheme 2.

A. K. Yadav et al. / Tetrahedron Letters 50 (2009) 5031–5034
5033
Table 2
Yield of the compounds 2a–e
the contents were neutralized by 10% aqueous sodium bicarbonate solution
and extraction was carried out with ethyl acetate (3 ꢀ 10 mL). The solvent was
removed under reduced pressure (5 mm of Hg). The pasty mass, thus obtained,
was extracted with diethyl ether (3 ꢀ 10 mL), dried over anhydrous sodium
sulphate and ether was distilled. The product, so obtained, was purified by
crystallization with ethanol/column chromatography (Merck Silica gel 60–120
mesh). The ionic liquid layer was washed with water (3 ꢀ 5 mL) and kept for
2 h at 80–85 °C under reduced pressure (5 mm of Hg). This ionic liquid was
used in recycling.
Product
R1
R2
R3
R4
Yielda (%)/time (min)
[BMIM]BF4 [MOEMIM]TFA
2a
2b
2c
2d
2e
H
H
5-Me
6-Me
8-Me
H
H
H
7-Me
H
Cl
F
F
F
F
Cl
F
F
F
F
72/90
80/90
85/90
90/90
86/90
80/80
87/80
92/80
94/70
90/80
20. Details of analytical data of compound 1a–i are presented below.
Compound 1a. 2-(20-Chlorophenyl)-3-(phenyl)-1,3-thiazolidin-4-one: white
solid, mp 117–118 °C, characteristic IR (KBr pellet, cmꢁ1)1670,740. 1H NMR
2
4
a
(300 MHz, CDCl3) d 3.80 (d, 1H, JHH = 15 Hz, 5-HA), 4.04 (dd, 1H, JHH = 2.0 Hz
and 2JHH = 15.2 Hz 5-HB), 6.90–7.31 (m, 10H, Ar–H and 2-H). 13C NMR (75 MHz,
CDCl3) 166.10, 165.20, 140.10, 138.20, 136.10, 134.20, 130.20, 128.10, 127.40,
126.30, 121.0, 120.10, 119.50, 118.70, 48.50. Anal. Calcd for C15H12ClNOS: C,
62.14; H, 4.17, N, 4.83. Found: C, 62.26; H, 4.25; N, 4.92.
Isolated yield after purification.
Table 3
Recyclability data for product 1e and 2e
Compound 1b. 2-(20-Chlorophenyl)-3-(300-methylphenyl)-1,3-thiazolidin-4-
one: white solid, mp 127–128 °C, characteristic IR (KBr pellet, cmꢁ1) 1675,
2
745. 1H NMR (300 MHz, CDCl3) d 2.60(s, 3H, CH3), 3.95(d, 1H, JHH = 15 Hz, 5-
Product
Cycle
Yield (%)/time (min)
HA), 4.08 (dd, 1H, 4JHH = 2–1 Hz and 2JHH = 15.5 Hz, 5-HB), 6.92–7.26 (m, 9H, Ar–
H and 2-H). 13CNMR (75 MHz, CDCl3) d 166.70, 165.20, 139.90, 137.24, 134.60,
130.10, 128.80, 128.30, 126.80, 125.10, 124.24, 122.72, 120.10, 118.10, 80.20,
49.10. Anal. Calcd for C16H14Cl NOS: C, 63.22; H, 4.64; N, 4.61. Found: C, 63.15;
H, 4.52; N, 4.51.
[BMIM]BF4
[MOEMIM]TFA
1e
1e
1e
2e
2e
2e
0
1
2
0
1
2
88/90
85/90
81/90
90/90
85/90
81/90
92/80
87/80
83/80
94/70
90/70
85/70
Compound 1c. 2-(20,60-Dichlorophenyl)-3-(300-methylphenyl)-1,3-thiazolidin-
4-one: white solid, mp 132–133 °C (lit.17, 129–132 °C), characteristic IR (KBr
pellet, cmꢁ1) 1675, 750. 1H NMR (300 MHz, CDCl3) d 2.75 (s, 3H, CH3), 3.98 (d,
2
4
2
1H, JHH = 15.5 Hz, 5-HA), 4.10 (dd, 1H, JHH = 2.1 Hz and JHH = 15.5 Hz, 5-HB),
6.98–7.30 (m, 8H, Ar–H and 2-H). 13C NMR (75 MHz, CDCl3) d 170.10, 168.20,
150.10, 147.20, 142.10, 140.20, 138.30, 137.20, 136.20, 130.34, 128.28, 127.20,
122.32, 120.14, 86.10, 48.90. Anal. Calcd for C16H13Cl2 NOS: C, 56.77; H, 3.87;
N, 4.14. Found: C, 56.60; H, 4.02; N, 4.25.
Acknowledgments
Compound 1d. 2-(20-Fluorophenyl)-3-(300-methoxyphenyl)-1,3-thiazolidin-4-
one: white solid, mp 121–122 °C, characteristic IR (KBr pellet, cmꢁ1), 1680,
750. 1H NMR d 3.82 (s, 3H, -OCH3); 3.95 (d, 1H, 2JHH = 15.5 Hz, 5-HA), 4.16 (dd,
We thank Head, Chemistry Department, University of Rajas-
than, Jaipur for providing laboratory facilities. We are grateful to
CDRI, Lucknow for some analytical data. Financial assistance from
UGC, New Delhi is thankfully acknowledged.
4
2
1H, JHH = 2.5 Hz and JHH = 15.5 Hz, 5-HB), 6.99–7.38 (m, 9H, Ar–H and 2-H).
13C NMR (75 MHz, CDCl3) d 168.20, 166.20, 158.10, 154.24, 150.30, 146.10,
144.20, 139.10, 138.10, 136.10, 134.10, 128.10, 122.20, 85.20, 84.10, 82.10.
Anal. Calcd for C16H14FNO2S: C, 63.33; H, 4.65; N, 4.61. Found: C, 63.20; H,
4.55; N, 4.52.
Compound 1e. 2-(20,60-Difluorophenyl)-3-(300-methoxyphenyl)-1,3-thiazolidin-
4-one: White solid, mp 100–101 °C, (lit.17, 100–102 °C), Characteristic IR (KBr
pellet, cmꢁ1), 1690, 1010. 1H NMR (300 MHz, CDCl3) d 3.75 (s, 3H, -OCH3), 3.89 (d,
References and notes
2
4
2
1. Barreca, M. L.; Balzarini, J.; Chimirri, A.; De Clercq, E.; De Luca, L.; Holtje, H. D.;
Holtje, M.; Monforte, A. M.; Montorte, P.; Pannecouque, C.; Rao, A.; Zappala, M.
J. Med. Chem. 2002, 45, 5410. and references cited therein.
2. Chimirri, A.; Grasso, S.; Monforte, A. M.; Monforte, P.; Zappala, M. Il Farmaco
1991, 46, 817.
1H, JHH = 15.5 Hz, 5-HA), 4.15 (dd, 1H, JHH = 2.1 Hz and JHH = 15.5 Hz, 5-HB),
6.58 (d, 1H, JHH = 2.0 Hz,2-H), 6.75–7.25 (m, 7H, Ar–H). 13C NMR (75 MHz,
4
CDCl3) d 172.40, 169.30, 162.40, 158.10, 156.20, 153.10, 148.40, 138.30, 135.40,
128.10, 127.10, 126.10, 120.30, 82.48, 79.10, 74.50, Anal. Calcd for
C16H13F2NO2S: C, 59.78; H, 4.07; N, 4.36. Found: C, 59.87; H, 3.93; N, 4.27.
Compound 1f. 3-(40-Chloropyridin-20-yl)-2-(200,600-difluorophenyl)-1,3-thiazoli-
din-4-one: white solid, mp 128–129 °C, characteristicIR (KBr pellet, cmꢁ1), 1700,
1020. 1H NMR (300 MHz, CDCl3) d 3.80 (d, 1H, 2JHH = 15.5 Hz, 5-HA), 4.26 (dd, 1H,
3. Chimirri, A.; Grasso, S.; Montorte, A. M.; Monforte, P.; Zappala, M. Il Farmaco
1991, 46, 925.
4. Chimirri, A.; Grasso, S.; Monforte, P.; Rao, A.; Zappala, M.; Monforte, A. M.;
Pannecouque, C.; Witvrouw, M.; Balzarini, J.; De Clercq, E. Antiviral Chem.
Chemother. 1999, 10, 211. and references cited therein.
5. Yildiz-Oren, I.; Yalcin, I.; Aki-Sener, E.; Carturk, N. Eur. J. Med. Chem. 2004, 39,
291.
6. Yamato, M. J. Pharm. Soc. Jpn. 1992, 112, 81.
7. Benazzouz, A.; Boraud, T.; Dubedat, P.; Boireu, A.; Stutzmann, J. M.; Gross, C.
Eur. J. Pharmacol. 1995, 284, 299.
8. Kumar, D.; Jacob, M. R.; Reynolds, M. B.; Kerwin, S. M. Bioorg. Med. Chem. 2002,
10, 3997.
9. Evans, D. A.; Sacks, C. E.; Kleschick, W. A.; Taber, T. R. J. Am. Chem. Soc. 1979,
101, 6789.
10. Figge, A.; Altenbach, H. J.; Brauer, D. J.; Tielmann, P. Tetrahedron: Asymmetry
2002, 11, 137.
11. So, Y. H.; Heeschem, J. P. J. Org. Chem. 1997, 62, 3552.
12. Villemin, D.; Hammadi, M.; Martin, B. Synth. Commun. 1996, 26, 2895.
13. Terashima, M.; Ishii, M. Synthesis 1982, 484.
2
3
4JHH = 1.4 Hz and JHH = 16.0 Hz, 5-HB), 6.86 (dd, 1H, JHH = 7.9 Hz and
3JHH = 8.20 Hz 400-H), 7.06 (d, 1H, JHH = 1.4 Hz, 2-H), 7.18–7.28 (m, 2H, 300-H
4
and 50-H), 7.50 (m, 2H, 30-H and 50-H), 8.30 (d,1H, 3JHH = 8.1 Hz, 60-H). 13C NMR
(75 MHz, CDCl3)d172.18, 170.60, 168.20, 165.25, 160.15, 150.10, 146.20, 141.20,
140.10, 138.10, 136.10, 128.10, 78.10, 87.10. Anal. Calcd for C14H9ClF2N2OS: C,
51.43; H, 2.77; N, 8.57. Found: C, 51.34; H, 2.66; N, 8.43.
Compound 1g. 3-(40-Bromopyridin-20-yl)-2-(200,600-difluorophenyl)-1,3-thiaz-
olidin-4-one: pale yellow solid, mp 130–131 °C, (lit.1 126–130 °C),
characteristic IR (KBr pellet, cmꢁ1) 1710, 1570, 1010. 1H NMR (300 MHz,
2
4
CDCl3) d 3.86 (d, 1H, JHH = 16.0 Hz, 5-HA), 4.25 (dd, 1H, JHH = 1.5 Hz and
2JHH = 16.0 Hz, 5-HB), 6.86 (dd, 1H, 3JHH = 8.0 Hz and 3JHH = 8.2 Hz, 400-H), 7.10 (d,
1H, 4JHH = 1.4 Hz, 2-H), 7.18–7.28 (m, 2H, 300-H and 500-H), 7.55 (m, 2H, 30-H and
50-H), 8.30 (d,1H, 3JHH = 8.1 Hz, 60-H). 13C NMR (75 MHz, CDCl3) d 170.10, 166.10,
160.18, 158.18, 151.15, 146.18, 142.35, 139.20, 136.10, 133.15, 132.15, 128.25,
86.10, 78.10. Anal. Calcd for C14H9BrF2N2OS: C, 45.27; H, 2.44; N, 7.54. Found: C,
45.21, H, 2.34; N, 7.43.
Compound 1h. 2-(20-Chloro-60-fluoro-30-methylphenyl)-3-(400-methylpyr-
imidin-200-yl)-1,3-thiazolidin-4-one: White solid, mp 125–126 °C, (lit.17
14. Hein, D. W.; Alheim, R. J.; Leavitt, J. J. Am. Chem. Soc. 1957, 79, 427.
15. Salehi, P.; Dabiri, M.; Zolfigol, M. A.; Otokesh, S.; Baghbanzadeh, M. Tetrahedron
Lett. 2006, 47, 2557.
16. Maradole, M. B.; Allam, S. K.; Mandha, A.; Chandramouli, G. V. P. Arkivoc 2008,
42.
)
126 °C); Characteristic IR (KBr pellet, cmꢁ1 1690, 1565,1030. 1H NMR
(300 MHz, CDCl3) d 2.18 (s, 3H, CH3) and 2.40 (s, 3H, CH3), 3.90 (d, 1H,
2JHH = 15.8 Hz, 5-HA), 4.25 (dd, 1H, 4JHH = 2.0 Hz and 2JHH = 15.7 Hz, 5-HB), 6.88–
8.54 (m, 5H, Ar–H, 40,50, 500,600). 13C NMR (75 MHz, CDCl3) d 173.10, 172.20,
166.30, 162.10, 157.15, 152.20, 148.15, 142.10, 136.15, 132.15, 128.25, 86.10,
76.10, 49.10, 48.20. Anal. Calcd for C15H13ClFN3OS: C,53.30; H, 3.88; N, 12.44.
Found: C, 53.26; H, 3.72; N, 12.37.
17. Rao, A.; Chimirri, A.; Ferro, S.; Monforte, A. M.; Montorte, P. M.; Zappala, M.
Arkivoc 2004, 147.
18. [BMIM]BF4 and [MOEMIM]TFA have been synthesized according to the
reported method, for example, Bonahote, P.; Dias, Ana-Paula; Papageorgiou,
N.; Kalyansundram, K.; Graztel, M. Inorg. Chem. 1996, 35, 1168.
Compound 1i. 2-(20,60-Dichlorophenyl)-3-(400,600-dimethylpyrimidin-200-yl)-1,3-
thiazolidin-4-one: white solid, mp 201–202 °C, (lit.17 200–202 °C), characteristic
IR (KBr pellet, cmꢁ1) 1710, 810,720. 1H NMR (300 MHz, CDCl3) d 2.39 (s, 6H, -
19. Typical experimental procedure for synthesis of 1a–i:
A
mixture of
heteroaromatic/aromatic amine (3 mmol), aromatic aldehyde (3 mmol) and
2-mercaptoacetic acid (6 mmol) and ionic liquid (5 mL) was taken in a round
bottom flask with provision to carry out the reaction under nitrogen
atmosphere. The contents of the flask were stirred magnetically at 80 2 °C.
The progress of the reaction was monitored on TLC plate (Merck Silica gel 60
F254 plates) in petroleum ether-ethyl acetate (8:2) and visualization was
accomplished in a iodine chamber/UV-light. After completion of the reaction,
2
4
CH3), 3.92 (d, 1H, JHH = 15.8 Hz, 5-HA), 4.20 (dd, 1H, JHH = 1.9 Hz and
2JHH = 15.8 Hz, 5-HB), 6.70–7.30 (m, 4H, 30,40, 50 and 500), 7.50 (d, 1H,
4JHH = 1.9 Hz, 2-H). 13C NMR (75 MHz, CDCl3) d 166.10, 152.10, 146.10, 143.20,
142.10, 138.10, 137.20, 136.10, 132.10, 86.10, 78.20, 66.20, 65.10, 62.10, 60.17.
Anal. Calcd for C15H13Cl2N3OS: C, 50.82; H, 3.69; N, 11.86. Found: C, 50.72; H,
3.60; N, 11.77.

5034
A. K. Yadav et al. / Tetrahedron Letters 50 (2009) 5031–5034
2
4
21. Typical experimental procedure for synthesis of 1-aryl-1H,3H-thiazolo[3,4-
a]benzimidazoles (2a–e): A mixture of 1,2-phenylenediamine (3 mmol), aromatic
aldehyde (3 mmol), 2-mercaptoacetic acid (6 mmol) was taken in round bottom
flask. The reaction was performed in the same way as described above.
5), 4.35 (d, 1H, JHH = 14.2 Hz, 3-HA), 4.69 (dd, 1H, JHH = 1.9 Hz and
2JHH = 14.2 Hz, 3-HB), 6.78–7.36 (m, 7H, Ar–H and 1-H). 13C NMR (75 MHz,
CDCl3) d 162.10, 160.15, 157.15, 155.21, 151.15, 149.10, 146.20, 145.10, 143.20,
139.15, 128.15, 122.85, 111.15, 95.10, 86.15, 66.10. Anal. Calcd for C16H12F2N2S:
C, 63.57; H, 4.00; N, 9.26. Found: C, 63.46; H, 3.89; N, 9.15.
22. Details of analytical data of compound 2a–e are given below.
Compound 2a. 1–(20,60-Dichlorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole:
pale yellow, mp 132–134 °C, characteristic IR (KBr pellet, cmꢁ1) 1610, 780, 710.
Compound 2d. 1-(20,60-Difluorophenyl)-6,7-dimethyl-1H,3H-thiazolo[3,4-a]-
benzimidazole: light yellow solid, mp 177–179 °C, (lit.17 178–179 °C),
characteristic IR (KBr pellet, cmꢁ1) 1630, 1025, 810. 1H NMR (300 MHz, CDCl3)
d 2.26 (s, 3H, 7-CH3), 2.34 (s, 3H, 6-CH3), 4.42 (d, 1H, 2JHH = 14.5 Hz, 3-HA), 4.69
(dd, 1H, 4JHH = 2.1 Hz and 2JHH = 14.5 Hz, 3-HB), 6.76–7.73(m, 6H, Ar–H and 1-H).
13C NMR (75 MHz, CDCl3) d 168.15, 166.10, 162.15, 155.15, 147.15, 145.50,
140.10, 138.11, 133.25, 130.55, 128.55, 122.15, 124.15, 94.15, 88.20, 56.15,
49.55. Anal. Calcd for C17H14F2N2S: C, 64.52; H, 4.46; N, 8.85. Found: C, 64.45; H,
4.38; N, 8.78.
2
1H NMR (300 MHz, CDCl3) d 4.26 (d, 1H, JHH = 14.3 Hz, 3-HA), 4.52 (dd, 1H,
2
4JHH = 1.8 Hz and JHH = 14.4 Hz, 3-HB), 6.70–7.72 (m, 8H, Ar–H and 1-H). 13C
NMR (75 MHz, CDCl3) d 160.10, 162.10, 160.10, 158.20, 156.10, 152.30, 149.40,
138.10, 136.10, 135.20, 126.30, 125.80, 123.30, 76.10, 72.20. Anal. Calcd for
C15H10Cl2N2S: C, 56.05; H, 3.13; N, 8.72. Found: C, 55.92; H, 3.08; N, 8.61.
Compound 2b. 1-(20,60-Difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole:
pale yellow, mp 141–142 °C, characteristic IR (KBr pellet, cmꢁ1) 1615, 1030. 1
H
2
NMR (300 MHz, CDCl3) d 4.30 (d, 1H, JHH = 14.5 Hz, 3-HA), 4.58 (dd, 1H,
Compound 2e. 1-(20,60-difluorophenyl)-8-methyl-1H,3H-thiazolo[3,4-a]benz-
imidazole: white solid, mp 149–150 °C, (lit17 149–150 °C), characteristic IR
(KBr pellet, cmꢁ1) 1625, 1040, 815. 1H NMR (300 MHz, CDCl3) d 2.32 (s, 3H, 8-
CH3), 4.30 (d, 1H, JHH = 14.2 Hz, 3-HA), 4.61(dd, 1H, JHH = 1.7 Hz and
2JHH = 14.2 Hz, 3-HB), 6.90–7.59 (m, 7H, Ar–H and 1-H). 13C NMR (75 MHz,
CDCl3) d 162.10, 160.11, 157.15, 155.28, 150.12, 149.11, 147.25, 143.10, 140.10,
136.10, 133.28, 127.10, 110.25, 93.15, 78.10, 49.10. Anal. Calcd for C16H12N2F2S:
C, 63.5; H, 4.00; N, 9.26. Found: C, 63.40; H, 3.91; N, 9.18.
2
4JHH = 1.8 Hz and JHH = 14.5 Hz, 3-HB), 6.75–7.76 (m, 8H, Ar–H and 1-H). 13C
NMR (75 MHz, CDCl3) d 168.10, 166.30, 161.25, 160.11, 158.11, 140.12, 137.10,
136.50, 128.50, 122.10, 120.30, 116.10, 90.15, 82.10, 72.15. Anal. Calcd for
C15H10F2N2S: C, 62.46; H, 3.49; N, 9.71. Found: C, 62.38; H, 3.39; N, 9.69.
Compound 2c. 1-(20,60-Difulorophenyl)-5-methyl-1H,3H-thiazolo[3,4-a]benz-
imidazole: White solid, mp 159–161 °C, (lit.17 159–161 °C), Characteristic IR
(KBr pellet, cmꢁ1) 1630, 1030, 805. 1H NMR (300 MHz, CDCl3) d 2.68 (s, 3H, CH3-
2
4