Solvent-free synthesis of functionalized 2,3-dihydrothiazoles from isothiocyanates, primary alkylamines, and 2-chloro-1,3-dicarbonyl compounds

Article abstract of DOI:10.1080/17415993.2010.485645

A simple one-pot synthesis of 3-alkyl-4-methyl-2-phenylimino-2,3- dihydrothiazoles from the reaction of phenylisothiocyanate, primary alkylamines and 2-chloro-1,3-dicarbonyl compounds under solvent-free conditions is described.

Full text of DOI:10.1080/17415993.2010.485645

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Solvent-free synthesis of functionalized
2,3-dihydrothiazoles from
isothiocyanates, primary alkylamines,
and 2-chloro-1,3-dicarbonyl compounds
Issa Yavari a , Tayebeh Sanaeishoar a , Maryam Ghazvini a & Nasir
Iravani a
a Department of Chemistry, Science and Research Campus, Islamic
Azad University, Ponak, Tehran, Iran
Published online: 26 May 2010.
To cite this article: Issa Yavari , Tayebeh Sanaeishoar , Maryam Ghazvini & Nasir Iravani (2010):
Solvent-free synthesis of functionalized 2,3-dihydrothiazoles from isothiocyanates, primary
alkylamines, and 2-chloro-1,3-dicarbonyl compounds, Journal of Sulfur Chemistry, 31:3, 169-176
To link to this article: http://dx.doi.org/10.1080/17415993.2010.485645
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Journal of Sulfur Chemistry
Vol. 31, No. 3, June 2010, 169–176
Solvent-free synthesis of functionalized 2,3-dihydrothiazoles
from isothiocyanates, primary alkylamines, and
2-chloro-1,3-dicarbonyl compounds
Issa Yavari*, Tayebeh Sanaeishoar, Maryam Ghazvini and Nasir Iravani
Department of Chemistry, Science and Research Campus, Islamic Azad University, Ponak, Tehran, Iran
(Received 28 January 2010; final version received 11 April 2010)
A simple one-pot synthesis of 3-alkyl-4-methyl-2-phenylimino-2,3-dihydrothiazoles from the reaction of
phenylisothiocyanate, primary alkylamines and 2-chloro-1,3-dicarbonyl compounds under solvent-free
conditions is described.
Keywords: 2,3-dihydrothiazole; isothiocyanate; primary alkylamine, 1,3-dicarbonyl compound; solvent-
free
1. Introduction
Thiazoles and their derivatives exhibit various biological activities such as antiviral, antimicrobial,
anti-inflammatory, and antituberculosis (1–3). The thiazolium ring present in vitamin B1 serves
as an electron sink, and its coenzyme form is important for the decarboxylation of α-keto-acids
(4). Some thiazolines show interesting anti-HIV or anticancer activities and can inhibit cell divi-
sion (5). In view of the importance of thiazoles, several methods for their synthesis have been
developed. The most widely used method is the Hantzsch synthesis (6–8) involving the reaction
of α-halocarbonyl compounds with thioureas or thioamides. Recently, a synthesis of thiazol-2-
imine derivative from benzoylphenylthioureas and the in situ generated α-bromoketones obtained
by the reaction of enolizable ketones with 1,10-(ethane-1,2-diyl)dipyridinium bistribromide has
been reported (9, 10).
As part of our current studies on the synthesis of sulfur-containing organic compounds (11–14),
we describe an efficient method for the synthesis of functionalized 2,3-dihydrothiazoles under
solvent-free conditions. This new catalyst-free and one-pot synthetic method seems facile; work-
up procedure is easy and gives pure target compounds containing several potential centers for
further modification.
*Corresponding author. Email: yavarisa@modares.ac.ir
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415993.2010.485645
http://www.informaworld.com

170 I. Yavari et al.
2. Results and discussion
The reaction of primary alkylamines 1 with isothiocyanates 2 in the presence of α-chlorocarbonyl
compounds 3 proceeds smoothly at room temperature to produce 3-alkyl-4-methyl-2-arylimino-
2,3-dihydrothiazoles 4a–4t in good yields after purification (Scheme 1). In this procedure, we have
modified the Hantzsch method for thiazole synthesis via the reaction of unsymmetrical thioureas
(5, see Scheme 2) with α-chlorocarbonyl compounds. Thus, various thiourea derivatives were
prepared from 1 and 2. Functionalized 2,3-dihydrothiazoles 4 were obtained from the reaction
of these thioureas with 3. The structures of compounds 4a–4k were deduced from their IR,
1
1H NMR, and 13C NMR spectral data. The H NMR spectrum of 4a in CDCl3 showed nine
signals for methyl (δ = 1.28 and 2.54 ppm), methoxy (δ = 3.82 ppm), and methylene (δ = 4.22
and 5.21 ppm) protons along with signals (δ = 6.89–7.37 ppm) for the aromatic protons. The
imino and carbonyl resonances in the 13C NMR spectrum of 4a appear at 159.5 and 162.4 ppm,
respectively. The mass spectrum of 4a displayed the molecular ion peak at m/z = 382. The
1H NMR and 13C NMR spectra of 4b–4k were similar to those of 4a except for the side chains,
which exhibited characteristic resonances in the appropriate regions of the spectrum.
Mechanistically, the reaction starts with the formation of unsymmetrical thiourea derivative 5
from primary alkylamines and phenyl isothiocyanates. Subsequent nucleophilic alkylation of 5
with α-chloroketones 3 yields intermediate 6. This intermediate undergoes HCl elimination and
COR"
O
O
S
Solvent-free
r.t., 1–3h
R'
+
R-NH2
R'-N=C=S
+
R"
N
N
Cl
R
1
4
2
3
1, 2, 3, 4
Yield (%) of 4
R''
R
R'
a
b
c
81
90
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
4-MeOC6H4CH2
4-ClC6H4CH2
Ph
Ph
83
93
87
91
85
2-ClC6H4CH2
Ph
Ph
d
e
4-MeC6H4CH2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Bn
nBu
nPr
f
g
h
i
83
Et
Bn
nBu
cyclohexyl
Bn
75
92
99
85
90
95
90
87
Me
Me
j
k
Me
l
Me
OMe
PhCO
PhCO
PhCO
PhCO
PhCO
PhCO
PhCO
m
n
o
p
Et
nBu
cyclohexyl
Bn
OMe
OMe
OMe
OMe
OMe
OMe
q
85
90
86
80
PhCH(CH3)NH2
r
s
2-furfuryl
nBu
Bn
2-FC6H4CO
2-FC6H4CO
OMe
t
Scheme 1. The three-component one-pot synthesis of 2,3-dihydrothiazoles 4.

Journal of Sulfur Chemistry 171
subsequent intramolecular cyclization reaction to form the heterocyclic intermediate 8, which
generates 4 by elimination of water (Scheme 2).
COR"
Cl
S
S
O
_
R'
R'
+
R
2
3
1
HCl
N
N
NH NH
H
H
R
5
6
COR"
COR"
OH
S
S
_
R'
H2O
O
NH
R'
4
N
N
N
R
R
8
7
Scheme 2. Plausible mechanism for the formation of 2,3-dihydrothiazoles 4.
3. Conclusions
We have described a convenient route to functionalized 3-alkyl-4-methyl-2-phenylimino-2,3-
dihydrothiazoles from primary alkylamines and phenylisothiocyanate in the presence of α-
chloroketones. The advantage of the present procedure is that the reaction is performed under
solvent-free conditions by simply mixing the starting materials. The procedure described
here also provides an efficient one-pot methodology for the preparation of functionalized
2,3-dihydrothiazoles.
4. Experimental
4.1. General
Primary alkylamines 1, isothiocyanates 2, and α-halocarbonyl compounds 3 were obtained from
Fluka and were used without further purification; IR spectra: Shimadzu IR-460 spectrometer;
1H- and 13C-NMR spectra: Bruker DRX-300AVANC instrument in CDCl3 at 300 and 75 MHz,
respectively, δ in ppm, and J in Hz; EI-MS (70 eV): Finnigan-MAT-8430 mass spectrometer
in m/z. Elemental analyses (C, H, and N) were performed with a Heraeus CHN-O-Rapid
analyzer.
4.2. General procedure for the preparation of compounds 4
A mixture of 0.27 g of 2 (2 mmol) and the primary alkylamine 1 (2 mmol) was stirred at r.t. for
20 min. Then, α-halocarbonyl 3 (2 mmol) was added to the reaction mixture and stirred at r.t.After
completion of the reaction [1–3 h; TLC (AcOEt/hexane 2:1)], the reaction mixture was purified
by column chromatography [silica gel (230–240 mesh; Merck), hexane/AcOEt 4:1)].

172 I. Yavari et al.
4.2.1. Ethyl 3-(4-methoxybenzyl)-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-
carboxylate (4a)
Dark yellow oil, yield: 0.61 g (81%). IR (KBr): 1690 (C O), (C N)cm−1. 1H NMR: 1.28 (3H,
=
=
3
3
t, J = 7.1 Hz, Me), 2.54 (3H, s, Me), 3.82 (3H, s, MeO), 4.22 (2H, q, J = 7.1 Hz, CH2O),
5.21 (2H, s, CH2), 6.89 (2H, d, 3J = 8.0 Hz, 2CH), 7.08 (2H, d, 3J = 8.0 Hz, 2CH), 7.09 (1H, d,
3J = 8.0 Hz, CH), 7.27 (2H, d, 3J = 8.0 Hz, 2CH), 7.37 (2H, t, 3J = 8.0 Hz, 2CH). 13C NMR:
13.7 (Me), 14.7 (Me), 47.2 (CH2), 55.7 (MeO), 61.1 (CH2O), 100.1 (C), 114.6 (2CH), 121.7
(CH), 123.9 (2CH), 128.6 (2CH), 129.9 (2CH), 147.4 (C), 150.9 (C), 156.1 (C), 158.1 (C), 159.5
+
=
=
(C N), 162.4 (C O). EI-MS: m/z (%) = 382 (M , 56), 290 (8), 233 (8), 197 (49), 121 (100),
103 (7), 91 (11), 77 (22). Anal. Calcd for C21H22N2O3S (382.47): C, 65.95%; H, 5.80%; N,
7.32%; found: C, 65.73%; H, 5.93%; N, 7.42%.
4.2.2. Ethyl 3-(4-chlorobenzyl)-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate
(4b)
Dark yellow oil, yield: 0.69 g (90%). IR (KBr): 1694 (C O), 1610 (C N)cm−1. 1H NMR: 1.29
(3H, t, 3J = 7.1 Hz, Me), 2.51 (3H, s, Me), 4.22 (2H, q, 3J = 7.1 Hz, CH2O), 5.23 (2H, s, CH2),
7.04–7.12 (3H, m, 3CH), 7.21–7.32 (4H, m, 4CH), 7.38–7.46 (2H, m, 2CH). 13C NMR: 13.6 (Me),
14.7 (Me), 49.1 (CH2), 61.2 (CH2O), 99.8 (C), 121.6 (CH), 124.1 (2CH), 125.8 (2CH), 128.1
=
=
=
=
(2CH), 128.5 (2CH), 129.1 (C), 129.4 (C), 129.9 (C), 130.8 (C), 156.1 (C N), 165.6 (C O).
EI-MS: m/z (%) = 388 (M++2, 14), 386 (M+, 43), 203 (12), 201 (38), 127 (33), 125 (100),
77 (22). Anal. Calcd for C20H19ClN2O2S (386.89): C, 62.09%; H, 4.95%; N, 7.24%; found: C,
62.43%; H, 5.13%; N, 7.32%.
4.2.3. Ethyl 3-(2-chlorobenzyl)-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate
(4c)
Dark yellow oil, yield: 0.64 g (83%). IR (KBr): 1701 (C O), 1614 (C N) cm−1. 1H NMR: 1.31
(3H, t, 3J = 7.0 Hz, Me), 2.47 (3H, s, Me), 4.24 (2H, q, 3J = 7.0 Hz, CH2O), 5.36 (2H, s, CH2),
7.03–7.11 (5H, m, 5CH), 7.32–7.42 (4H, m, 4CH). 13C NMR: 13.3 (Me), 14.9 (Me), 45.7 (CH2),
61.2 (CH2O), 100.6 (C), 121.6 (CH), 124.1 (2CH), 127.2 (CH), 127.7 (CH), 128.6 (2CH), 129.9
=
=
=
=
(CH), 130.1 (CH), 132.8 (C), 133.7 (C), 146.9 (C), 150.7 (C), 157.6 (C N), 162.4 (C O). EI-
MS: m/z (%) = 388 (M++2, 16), 386 (M+, 48), 203 (11), 201 (33), 127 (33), 125 (100), 77 (22).
Anal. Calcd for C20H19ClN2O2S (386.90): C, 62.09%; H, 4.95%; N, 7.24%; found: C, 62.33%;
H, 5.08%; N, 7.30%.
4.2.4. Ethyl 4-methyl-3-(4-methylbenzyl)-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate
(4d)
Dark yellow oil, yield: 0.68 g (93%). IR (KBr): 1701 (C O), 1613 (C N) cm−1. 1H NMR: 1.29
(3H, t, 3J = 7.1 Hz, Me), 2.36 (3H, s, Me), 2.52 (3H, s, Me), 4.22 (2H, q, 3J = 7.1 Hz, CH2O),
5.24 (2H, s, CH2), 7.07–7.12 (3H, m, 3CH), 7.16–7.19 (4H, m, 4CH), 7.34–7.39 (2H, m, 2CH).13C
NMR: 13.6 (Me), 14.7 (Me), 21.5 (Me), 47.5 (CH2), 61.1 (CH2O), 100.1 (C), 121.7 (CH), 123.9
=
=
=
(2CH), 127.1 (4CH), 129.9 (2CH), 133.6 (C), 137.7 (C), 147.5 (C), 150.9 (C), 158.1 (C N),
+
=
162.5 (C O). EI-MS: m/z (%) = 366 (M , 55), 274 (12), 233 (10), 181 (95), 105 (100), 102
(20), 77 (16). Anal. Calcd for C21H22N2O2S (366.48): C, 68.82%; H, 6.05%; N, 7.64%; found:
C, 68.49%; H, 6.13%; N, 7.72%.

Journal of Sulfur Chemistry 173
4.2.5. Ethyl 3-benzyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate (4e)
Dark yellow oil, yield: 0.61 g (87%); IR (KBr): 1702 (C O), 1613 (C N) cm−1; 1H NMR: 1.29
(3H, t, 3J = 7.0 Hz, Me), 2.52 (3H, s, Me), 4.22 (2H, q, 3J = 7.0 Hz, CH2O), 5.28 (2H, s, CH2),
7.06–7.09 (5H, m, 5CH), 7.32–7.39 (5H, m, 5CH). 13C NMR: 13.6 (Me), 14.7 (Me), 47.7 (CH2),
61.1 (CH2O), 100.2 (C), 121.7 (CH), 124.1 (2CH), 127.2 (CH), 128.1 (2CH), 129.3 (2CH), 129.9
=
=
=
=
(2CH), 136.6 (C), 147.3 (C), 150.9 (C), 158.1 (C N), 162.4 (C O). EI-MS: m/z (%) = 352
(M+, 31), 167 (76), 91 (100), 77 (16). Anal. Calcd for C20H20N2O2S (352.45): C, 68.16%; H,
5.72%; N, 7.95%; found: C, 68.01%; H, 5.65%; N, 7.92%.
4.2.6. Ethyl 3-butyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate (4f)
Dark yellow oil, yield: 0.65 g (87%). IR (KBr): 1699 (C O), 1612 (C N) cm−1. H NMR:
1
=
=
1.01 (3H, t, 3J = 6.8 Hz, Me), 1.28 (3H, t, 3J = 7.1 Hz, Me), 1.44 (2H, m, 3J = 6.8 Hz, CH2),
3
3
1.76 (2H, m, J = 6.8 Hz, CH2), 2.61 (3H, s, Me), 3.96 (2H, t, J = 6.8 Hz, CH2), 4.21 (2H,
3
q, J = 7.1 Hz, CH2O), 7.04–7.11 (3H, m, 3CH), 7.34–7.38 (2H, m, 2CH). 13C NMR: 13.4
(Me), 14.2 (Me), 14.8 (Me), 20.5 (CH2), 30.7 (CH2), 44.7 (CH2), 60.9 (CH2O), 99.9 (C), 121.7
=
=
(CH), 123.9 (2CH), 129.9 (2CH), 136.6 (C), 147.2 (C), 151.4 (C N), 162.6 (C O). EI-MS: m/z
(%) = 318 (M+, 100), 303 (10), 262 (39), 226 (19), 189 (15), 91 (10), 41 (17). Anal. Calcd for
C17H22N2O2S (318.43): C, 64.12%; H, 6.96%; N, 8.80%; found: C, 64.55%; H, 6.91%; N, 8.92%.
4.2.7. Ethyl 4-methyl-2-(phenylimino)-3-propyl-2,3-dihydrothiazole-5-carboxylate (4g)
Dark yellow oil, yield: 0.51 g (85%). IR (KBr): 1718 (C O), 1620 (C N) cm−1. 1H NMR: 0.93
(3H, t, 3J = 7.0 Hz, Me), 1.36 (3H, t, 3J = 7.1 Hz, Me), 1.68 (2H, m, 3J = 7.0 Hz, CH2), 2.54
(3H, s, Me), 3.46 (2H, t, 3J = 7.0 Hz, CH2), 4.22 (2H, q, 3J = 7.1 Hz, CH2O), 6.83–6.88 (3H,
m, 3CH), 7.36–7.42 (2H, m, 2CH). 13C NMR: 11.8 (Me), 12.5 (Me), 14.6 (Me), 22.2 (CH2), 52.5
=
=
(CH2), 61.8 (CH2O), 100.3 (C), 121.2 (CH), 128.9 (2CH), 130.1 (2CH), 136.4 (C), 146.9 (C),
+
=
=
152.8 (C N), 163.1 (C O). EI-MS: m/z (%) = 304 (M , 100), 119 (55), 185 (34), 77 (16).
Anal. Calcd for C16H20N2O2S (304.41): C, 63.13%; H, 6.62%; N, 9.20%; found: C, 63.44%; H,
6.81%; N, 9.37%.
4.2.8. Ethyl 3-ethyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-carboxylate (4h)
1
Dark yellow oil, yield: 0.48 g (83%). IR (KBr): 1699 (C O), 1612 (C N) cm−1. H NMR:
=
=
3
3
1.28 (3H, t, J = 7.1 Hz, Me), 1.37 (3H, t, J = 7.1 Hz, Me), 2.62 (3H, s, Me), 4.04 (2H, q,
3J = 7.1 Hz, CH2), 4.21 (2H, q, 3J = 7.1 Hz, CH2O), 7.05–7.11 (3H, m, 3CH), 7.34–7.39 (2H,
m, 2CH). 13C NMR 13.2 (Me), 13.8 (Me), 14.8 (Me), 39.9 (CH2), 61.1 (CH2O), 99.8 (C), 121.7
=
=
(CH), 123.9 (2CH), 129.9 (2CH), 146.8 (C), 151.3 (C), 157.5 (C N), 162.5 (C O). EI-MS: m/z
(%) = 290 (M+, 100), 262 (12), 186 (34), 114 (17), 105 (55), 77 (14), 70 (18), 42 (31). Anal.
Calcd for C15H18N2O2S (290.38): C, 62.04%; H, 6.25%; N, 9.65%; found: C, 62.07%; H, 6.16%;
N, 9.79%.
4.2.9. 1-(3-Benzyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-yl)ethanone (4i)
Dark yellow oil, yield: 0.48 g (75%), IR (KBr): 1775 (C O), 1633 (C N) cm−1. 1H NMR: 2.29
(3H, s, Me), 2.54 (3H, s, Me), 5.31 (2H, s, CH2), 7.07–7.11 (5H, m, 5CH), 7.28–7.41 (5H, m,
5CH). 13C NMR: 14.3 (Me), 30.5 (Me), 47.9 (CH2), 110.8 (C), 121.7 (2CH), 124.4 (CH), 127.0
=
=
=
(2CH), 128.1 (CH), 129.3 (2CH), 129.9 (2CH), 136.1 (C), 146.5 (C), 150.8 (C), 158.3 (C N),

174 I. Yavari et al.
+
=
189.6 (C O). EI-MS: m/z (%) = 322 (M , 55), 168 (69), 91 (100), 77 (26). Anal. Calcd for
C19H18N2OS (322.42): C, 70.78%; H, 5.63%; N, 8.69%; found: C, 70.93%; H, 5.83%; N, 8.82%.
4.2.10. 1-(3-Butyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-yl)ethanone (4j)
Dark yellow oil, yield: 0.52 g (92%). IR (KBr): 1771 (C O), 1622 (C N) cm−1. 1H NMR: 1.01
(3H, t, J = 7.0 Hz, Me), 1.44–1.48 (2H, m, CH2), 1.76–1.79 (2H, m, CH2), 2.26 (3H, s, Me)
=
=
3
2.63 (3H, s, Me), 3.99 (2H, t, 3J = 7.0 Hz, CH2N), 7.07 (2H, d, 3J = 7.3 Hz, 2CH), 7.10 (1H, t,
3J = 7.3 Hz, CH), 7.36–7.39 (2H, m, 2CH). 13C NMR: 14.1 (Me), 14.2 (CH2), 20.4 (Me), 30.5
(CH2), 30.6 (Me), 44.8(CH2), 109.9(C), 121.7 (2CH), 122.1 (C)+, 124.2 (C), 129.6 (CH), 129.9
=
=
(2CH), 146.5 (C N), 189.6 (C O). EI-MS: m/z (%) = 288 (M , 100), 133 (53), 135 (29), 77
(17). Anal. Calcd for C16H20N2OS (288.41): C, 66.63%; H, 6.99%; N, 9.71%; found: C, 66.97%;
H, 6.72%; N, 9.82%.
4.2.11. 1-(3-Cycloexyl-4-methyl-2-(phenylimino)-2,3-dihydrothiazole-5-yl)ethanone (4k)
1
Dark yellow oil, yield: 0.55 g (89%). IR (KBr): 1769 (C O), 1629 (C N) cm−1. H NMR:
1.21–2.20 (10H, m, 5CH2), 2.23 (3H, s, Me), 2.65 (3H, s, Me), 4.21 (1H, m, CH), 7.01 (2H,
d, 3J = 7.4 Hz, 2CH), 7.10 (1H, t, 3J = 7.4 Hz, CH), 7.35–7.39 (2H, m, 2CH). 13C NMR: 14.9
(Me), 25.5 (CH2), 26.7 (2CH2), 29.2 (Me), 30.8 (2CH2), 58.6 (CH), 109.5(C), 121.5 (2CH), 124.0
=
=
=
=
(C), 130.0 (CH), 130.1 (2CH), 147.2 (C), 151.5 (C N), 189.8 (C O). EI-MS: m/z (%) = 314
(M+, 100), 159 (53), 155 (33), 77 (36). Anal. Calcd for C18H22N2OS (314.45): C, 68.75%; H,
7.05%; N, 8.91%; found: C, 68.43%; H, 7.33%; N, 9.12%.
4.2.12. N-(5-Acetyl-3-benzyl-4-methylthiazole-2(3H)-yliden)benzamide (4l)
◦
−1
.
=
=
White powder, yield: 0.30 g (85%), mp: 132–134 C. IR (KBr): 1685 (C O), 1617 (C N) cm
1H NMR: 2.52 (3H, s, Me), 2.68 (3H, s, Me), 5.68 (1H, s, CH2), 7.29–7.39 (5H, m, 5CH), 7.42–
7.53 (3H, m, 3CH), 8.30–8.33 (2H, m, 2CH). 13C NMR: 13.3 (Me), 27.4 (Me), 49.9 (CH2N),
128.5 (2CH), 128.6 (2CH), 129.5 (2CH), 129.8 (2CH), 130.4 (CH), 131.6 (C), 132.7 (CH), 136.5
=
=
=
(C), 137.4 (C), 141.8 (C), 162.8 (C N), 175.5 (C O), 189.3 (C O). EI-MS: m/z (%) = 350
(M+, 46), 269 (16), 239 (23), 207 (34), 105 (100), 91 (13), 77 (20). Anal. Calcd for C20H18N2O2S
(350.11): C, 68.55%, H, 5.18%, N, 7.99%; found: C, 68.83%, H, 5.30%, N, 8.08%.
4.2.13. Methyl 2-(benzoylimino)-3-ethyl-4-methyl-2,3-dihydrothiazole-5-carboxylate (4m)
◦
−1
.
=
=
White powder, yield: 0.27 g (90%), mp: 138–140 C. IR (KBr): 1689 (C O), 1597 (C N) cm
1H NMR: δ = 1.46 (3H, t, 3JHH = 7.1 Hz, Me), 2.76 (3H, s, Me), 3.88 (3H, s, MeO), 4.40 (2H,
q, JHH = 7.1 Hz, CH2N), 7.43–7.55 (3H, m, 3CH), 8.35–8.35 (m, 2CH). 13C NMR: δ = 12.8
3
(Me), 14.0 (Me), 42.0 (CH2N), 52.4 (MeO), 108.2 (C), 128.4 (2CH), 129.7 (2CH), 132.1 (+CH),
=
=
=
137.0 (C), 144.1 (C), 162.9 (C N), 168.0 (C O), 175.6 (C O). EI-MS: m/z (%) = 304 (M , 9),
275 (35), 245 (26), 193 (17), 105 (100), 77 (45), 42 (8). Anal. Calcd for C15H16N2O3S (304.09):
C, 59.19%, H, 5.30%, N, 9.20%; found: C, 59.28%, H, 5.24%, N, 9.24%.
4.2.14. Methyl 2-(benzoylimino)-3-butyl-4-methyl-2,3-dihydrothiazole-5-carboxylate (4n)
◦
−1
.
=
=
White powder, yield: 0.31 g (95%), mp: 141–143 C. IR (KBr): 1710 (C O), 1601 (C N) cm
1H NMR: δ = 1.04 (3H, t, 3JHH = 7.3 Hz, Me), 1.51(2H, sextet, 3JHH = 7.5 Hz, CH2), 1.86 (3H,

Journal of Sulfur Chemistry 175
3
qui,3JHH = 7.5 Hz, CH2), 2.76 (3H, s, Me), 3.88 (3H, s, MeO), 4.34 (2H, q, JHH = 7.8 Hz,
CH2O), 7.44–7.55 (3H, m, 3CH), 8.32–8.35 (2H, m, 2CH). 13C NMR: 13.0 (Me), 14.1 (Me), 20.5
(CH2), 30.9 (CH2), 46.7 (CH2N), 52.4 (MeO), 110.2 (C), 128.5 (2CH), 129.7 (2CH), 132.1 (+CH),
=
=
137.0 (C), 144.4 (C), 163.0 (C=N), 168.0 (C O), 175.1 (C O). EI-MS: m/z (%) = 332 (M , 5),
264 (42), 222 (27), 164 (18), 105 (100), 77 (42), 72 (9), 59 (15). Anal. Calcd for C17H20N2O3S
(332.42): C, 61.42%, H, 6.06%, N, 8.43%; found: C, 61.35%, H, 6.12%, N, 8.38%.
4.2.15. Methyl 2-(benzoylimino)-3-cyclohexyl-4-methyl-2,3-dihydrothiazole-5-carboxylate
(4o)
◦
−1
.
=
=
White powder, yield: 0.32 g (90%), mp: 154–156 C. IR (KBr): 1718 (C O), 1620 (C N) cm
1H NMR: δ = 1.43–1.61 (4H, m, 2CH2), 1.80–1.99 (4H, m, 2CH2), 2.77 (3H, s, Me), 3.87 (3H,
s, MeO), 4.45 (2H, m, CH2N), 7.49–7.57 (3H, m, 3CH), 8.29–8.32 (2H, m, 2CH). 13C NMR:
12.8 (Me), 24.1 (2CH2), 25.8 (CH2), 26.3 (2CH2), 51.8 (MeO), 60.6 (CH2N), 109.2 (C), 128.6
=
=
=
(2CH), 129.3 (2CH), 132.0 (CH), 137.4 (C), 145.7 (C), 162.5 (C N), 167.5 (C O), 175.7 (C O).
EI-MS: m/z (%) = 358 (M+, 11), 276 (55), 248 (22), 199 (8), 105 (100), 77 (37), 59 (8). Anal.
Calcd for C19H22N2O3S (358.14): C, 63.66%, H, 6.19%, N, 7.82%; found: C, 63.42%, H, 6.15%,
N, 7.93%.
4.2.16. Methyl 2-(benzoylimino)-3-benzyl-4-methyl-2,3-dihydrothiazole-5-carboxylate (4p)
◦
−1
.
=
=
White powder, yield: 0.32 g (87%), mp: 148–150 C. IR (KBr): 1712 (C O), 1618 (C N) cm
1H NMR: 2.66 (3H, s, Me), 3.88 (3H, s, MeO), 5.66 (2H, s, CH2), 7.30–7.41 (1H, m, 5CH), 7.43–
7.51 (3H, m, 3CH), 8.30–8.32 (2H, m, 2CH). 13C NMR: 13.3 (Me), 49.9 (CH2N), 52.5 (MeO),
100.3 (C), 127.3 (CH), 128.5 (2CH), 128.6 (CH), 129.5 (2CH), 129.8 (2CH), 132.2 (CH), 135.6
=
=
=
(C), 136.7 (C), 144.8 (C), 162.8 (C N), 168.9 (C O), 175.3 (C O). EI-MS: m/z (%) = 358
(M+, 18), 267 (34), 298 (25), 255 (10), 105 (100), 77 (46), 59 (13). Anal. Calcd for C20H18N2O3S
(366.43): C, 65.55%, H, 4.95%, N, 7.64%; found: C, 65.33%, H, 5.04%, N, 7.75%.
4.2.17. Methyl 2-(benzoylimino)-4-methyl-3-(1-phenylethyl)-1,3-thiazole-5-carboxylate (4q)
◦
−1
.
=
=
White powder, yield: 0.32 g (85%), mp: 183–185 C. IR (KBr): 1698 (C O), 1614 (C N) cm
1H NMR: 2.14 (3H, d, 3J = 7.2 Hz, Me), 2.61 (1H, q, 3J = 7.2 Hz, CH2), 2.83 (3H, s, Me), 3.88
(3H, s, MeO), 5.66 (2H, s, CH2), 7.31–7.42 (5H, m, 5CH), 7.44–7.53 (3H, m, 3CH), 8.15–8.18
(2H, m, 2CH). 13C NMR: 13.9 (Me), 16.6 (Me), 51.9 (MeO), 56.2 (CH2N), 109.8 (C), 126.5
(2CH), 127.8 (CH), 128.4 (CH), 129.1 (2CH), 129.5 (2CH), 132.1 (CH), 137.1 (C),+140.1 (C),
=
=
=
145.7 (C), 162.4 (C N), 168.1 (C O), 174.2 (C O). EI-MS: m/z (%) = 380 (M , 19), 321
(8), 275 (35), 269 (22), 105 (100), 77 (29), 59 (17). Anal. Calcd for C21H20N2O3S (380.12): C,
66.29%, H, 5.30%, N, 7.36%; found: C, 66.48%, H, 5.21%, N, 7.47%.
4.2.18. Methyl2-(benzoylimino)-3-(furan-2-ylmethyl)-4-methyl-2,3-dihydrothiazole-5-
carboxylate (4r)
◦
−1
.
=
=
White powder, yield: 0.32 g (90%), mp: 149–151 C. IR (KBr): 1699 (C O), 1608 (C N) cm
1H NMR: 2.89 (3H, s, Me), 3.88 (3H, s, MeO), 5.56 (2H, s, CH2), 6.34–6.36 (1H, m, CH), 6.50–
6.51 (1H, m, CH), 7.37–7.38 (1H, m, CH), 7.46–7.55 (3H, m, 3CH), 8.36–8.38 (2H, m, 2CH). 13
NMR: 13.2 (Me), 42.7 (CH2N), 52.5 (MeO), 109.0 (C), 110.3 (CH), 111.2 (CH), 128.5 (2CH),
C
=
129.8 (2CH), 132.3 (CH), 136.8 (C), 143.1 (CH+), 144.5 (C), 148.6 (C), 162.9 (C N), 168.5
=
=
(C O), 175.0 (C O). EI-MS: m/z (%) = 356 (M , 10), 297 (23), 274 (17), 246 (28), 105 (100),

176 I. Yavari et al.
77 (17), 59 (10).Anal. Calcd for C18H16N2O4S (356. 40): C, 60.66%, H, 4.53%, N, 7.86%; found:
C, 60.35%, H, 4.59%, N, 7.98%.
4.2.19. Methyl 3-butyl-2-(2-fluorobenzoylimino)-4-methyl-2,3-dihydrothiazole-5-carboxylate
(4s)
◦
−1
.
=
=
White crystal, yield: 0.28 g (86%), mp: 157–159 C. IR (KBr): 1709 (C O), 1620 (C N) cm
1H NMR: δ = 1.01 (3H, t, JHH = 7.3 Hz, Me), 1.47 (2H, sextet, JHH = 7.4 Hz, CH2), 1.81
(2H, qui,3JHH = 7.5 Hz, CH2), 2.74 (3H, s, Me), 3.87 (3H, s, MeO), 4.30 (2H, q, 3JHH = 7.6 Hz,
CH2O), 7.10–7.23 (2H, m, 2CH), 7.46–7.49 (1H, m, 1CH), 8.15–8.20 (1H, m, CH). 13C NMR:
13.0 (Me), 14.1 (Me), 20.5 (CH2), 30.9 (CH2), 46.7 (CH2N), 52.4 (MeO), 110.3 (C), 117.2 (d,
3
3
2JCF = 22.7, CH), 124.0 (d,4JCF = 3.8, CH), 125.5 (d, JCF = 8.4, C), 132.5 (d, JCF = 20.7,
3
2
CH) , 133.3 (d, 3JCF = 8.8, CH), 144.5 (C), 162.6 (d, 1JCF = 257.0, C–F), 162.9 (C N), 164.3
=
3
+
=
=
=
(C N), 167.8 (C O), 173.0 (d, JCF = 4.3, C O). EI-MS: m/z (%) = 350 (M , 15), 292 (25),
222 (21), 123 (100), 105 (46), 77 (17), 72 (8), 59 (12). Anal. Calcd for C17H19FN2O3S (350. 41):
C, 58.27%, H, 5.47%, N, 7.99%; found: C, 58.16%, H, 5.59%, N, 8.18%.
4.2.20. Methyl 3-benzyl-2-(2-fluorobenzoylimino)-4-methyl-2,3-dihydrothiazole-5-carboxylate
(4t)
◦
−1
.
=
=
White powder, yield: 0.31 g (80%), mp: 140–142 C. IR (KBr): 1701 (C O), 1613 (C N) cm
1H NMR: 2.70 (3H, s, Me), 3.88 (3H, s, MeO), 5.77 (2H, s, CH2), 7.15–7.27 (2H, m, 2CH), 7.30–
7.42 (5H, m, 5CH), 7.52–7.55 (1H, m, CH), 8.11–8.16 (1H, m, CH). 13C NMR: 12.5 (Me), 49.6
2
(CH2N), 52.0 (MeO), 109.6 (C), 117.3 (d, JCF = 21.7, CH), 123.5 (d, 2JCF = 20.1, C), 124.1
(d, 4JCF = 3.9, CH), 127.2 (2CH), 128.2 (CH), 129.5 (2CH), 130.4 (C), 133.5 (d, 3JCF = 12.0,
CH), 135.2 (d, 3JCF = 10.8, CH), 145.6 (C), 162.3 (C=N), 164.9 (d, 1JCF = 264.0, C–F), 172.5
3
+
=
=
(C O), 176.9 (d, JCF = 4.5, C O). EI-MS: m/z (%) = 384 (M , 21), 293 (34), 255 (18), 225
(10), 123 (100), 105 (72), 77 (37), 59 (8). Anal. Calcd for C20H17FN2O3S (384.09): C, 62.49%,
H, 4.46%, N, 7.29%; found: C, 62.75%, H, 4.49%, N, 7.38%.
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