Formation of thiazol-2(3H)-imines by reaction of α-amino acids, aroylisothiocyanates, and α-bromoketones in an ionic liquid

Article abstract of DOI:10.1016/j.cclet.2013.11.009

An efficient one-pot synthesis of functionalized thiazol-2(3H)-imines by a three-component reaction between aroylisothiocyanates, α-amino acids, and α-bromoketones in an ionic liquid is described.

Full text of DOI:10.1016/j.cclet.2013.11.009

Chinese Chemical Letters 25 (2014) 119–122
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Original article
Formation of thiazol-2(3H)-imines by reaction of
a-amino acids,
aroylisothiocyanates, and
a-bromoketones in an ionic liquid
b
c
Ashraf S. Shahvelayati a, , Issa Yavari , Akram S. Delbari
*
a Department of Chemistry, Shahr-e Ray Branch, Islamic Azad University, Tehran 18155-144, Iran
b Department of Chemistry, Tarbiat Modares University, Tehran 14115-175, Iran
c Department of Chemistry, Islamshahr Branch, Islamshahr 33135-369, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
An efficient one-pot synthesis of functionalized thiazol-2(3H)-imines by a three-component reaction
between aroylisothiocyanates, -amino acids, and -bromoketones in an ionic liquid is described.
Received 11 July 2013
a
a
Received in revised form 15 October 2013
Accepted 25 October 2013
Available online 7 December 2013
ß 2013 Ashraf S. Shahvelayati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Aroylisothiocyanate
a
-Amino acids
S-Nucleophile
-Bromoketones
a
Ionic liquid
1. Introduction
conventional solvents. Thus, as a result of their ‘green’ credentials
and potential to enhance rate and selectivity, ILs have been used as
Thiazoles are an important group of heterocyclic compounds,
several derivatives of which have been found to possess useful
bioactivity such as anti-tumor [1], anti-fungal [2], anti-inflamma-
tory, and anti-microbial properties [3]. In recent years, thiazole
derivatives have attracted considerable attention because of their
bioactivity and many applications in organic and medicinal
chemistry [4,5]. A number of thiazolidenebenzenesulfonamide
derivatives are reported as a novel class of non-nucleoside HIV-1RT
inhibitors [6]. Thiazole-5-hydroxamic acids have been described as
novel histone deacetylase inhibitors [7].
solvents in chemical transformations [11–13].
As part of our current studies on the development of new routes
in heterocyclic synthesis [14–17], we report an efficient one-pot
synthesis of functionalized thiazol-2(3H)-imines 4a–l in good
yields by a three-component reaction between aroylisothiocya-
nates 1,
a-amino acids 2, and a-bromoketones 3 in 1-butyl-3-
methylimidazolium bromide [bmim]Br as a solvent at 50 8C
(Scheme 1).
2. Experimental
Although the Hantzsch process, in which an
a-halocarbonyl
compound is condensed with a thioamide, has been for decades the
method of choice for the synthesis of thiazoles [8], great effort has
been dedicated to more flexible procedures, and particularly to
that of thiazole ring formation in novel reaction media [9,10].
Ionic liquids (ILs) have attracted considerable attention as a
novel media in recent years due to their unique properties, such as
lack of measurable vapor pressure, non-flammability and recycla-
bility. Their high polarity and ability to dissolve both inorganic and
organic materials can result in enhanced rates of chemical
processes and can provide higher selectivity compared to
a
-Amino acids, aroylisothiocyanates, and a-bromoketones
were obtained from Fluka and were used without further
purification. Melting points were obtained on an Electrother-
mal-9100 apparatus. IR Spectra were recorded with a Shimadzu IR-
460 spectrometer. 1H NMR and 13C NMR spectra were recorded
with a Bruker DRX-300 Avance instrument using CDCl3 as the
deuterated solvent containing tetramethylsilane as internal
standard, at 300 MHz and 75 MHz, respectively;
d in parts per
million, J in hertz. EIMS (70 eV): Mass spectra were obtained with a
Finnigan-MAT-8430 mass spectrometer, in m/z. Elemental anal-
yses (C, H, N) were obtained with a Heraeus CHN-O-Rapid analyzer.
General procedure for the preparation of compounds 4: A
mixture of
a-amino acid 1 (1 mmol) and aroylisothiocyanate 2
*
Corresponding author.
E-mail address: avelayati@yahoo.com (A.S. Shahvelayati).
(1 mmol) was stirred in 1 mL of [bmim]Br for 1 h at 50 8C, and then
1001-8417/$ – see front matter ß 2013 Ashraf S. Shahvelayati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2013.11.009

120
A.S. Shahvelayati et al. / Chinese Chemical Letters 25 (2014) 119–122
Ar
Yiled (%)
R'
4
O
R
R
a
b
c
d
e
f
g
h
i
Ph
CO Et
2
H
76
79
86
R'
Ph
4-MeOC H
H
6
4
4
4
4
OH
N
Ph
4-BrC H
H
O
6
4
CO H
O
2
a
Ph
CO Et
Me
Me
Me
i-Pr
i-Pr
i-Pr
Me
Me
Me
[bmim]Br
o
96
2
S
+
+
Ph
4-MeOC H
6
94
97
92
89
96
80
85
83
Br
N
C
50
C
S
Ph
4-BrC H
R'
6
4
R
NH
Ar
N
2
Ph
CO Et
2
Ph
4-MeOC H
6
Ar
O
R
3
R'
CO Et
1
Ar
Ph
4-BrC H
2
6
4
j
k
l
p-Tolyl
p-Tolyl
p-Tolyl
CO Et
2
a
b
c
a
b
c
H
Me
i-Pr
a
b
Ph
p-Tolyl
2
4-MeOC H
6
4-MeOC H
6
4
4-BrC H
6
4
4-BrC H
6
4
a
4 d, yiled 96% in [bmim]Br for the first time, 90% in the second run, and
88% in the third run with recycled il; yiled 95% in [omim]Br
Scheme 1. Synthesis of compounds 4a–l.
a
-bromo-carbonyl compound 3 (1 mmol) was added. After stirring
7.66 (s, CH), 8.22 (d, 3J = 7.5 Hz, 2 CH), 11.21 (s, COOH); 13C-NMR
for 3 h, 5 mL of water was added and the mixture was extracted
with Et2O (3 Â 10 mL). The solvent from the mixture was
evaporated under reduced pressure to leave a residue that was
purified by column chromatography (SiO2; hexane/EtOAc = 4/1) to
afford pure 4. The ionic liquid can be reused after extraction from
the aqueous phase.
(75 MHz, CDCl3):d 14.5 (Me), 15.7 (Me), 56.2 (CH), 62.7 (OCH2),
121.5 (CH), 127.9 (2 CH), 128.5 (2 CH), 129.8 (CH), 132.5 (C), 136.3
(C), 159.0 (C55N), 168.2 (C55O), 174.2 (C55O), 174.8 (C55O). MS: m/z
(%) 348 (M+, 4), 276 (81), 105 (100), 77 (19), 73 (43), 45 (56). Anal.
Calcd. for C16H16N2O5S (348.37): C, 55.16; H, 4.63; N, 8.04. Found:
C, 55.5; H, 4.8; N, 8.2.
2-[4-(Ethoxycarbonyl)-2-(benzoylimino)thiazol-3(2H)-yl]ace-
tic acid (4a): Cream powder, yield: 0.25 g (76%); mp 176–178 8C; IR
(KBr, cmÀ1): nmax 3610–2950 (CO2H), 1752, 1721, 1666, 1601,
2-[2-(Benzoylimino)-4-(4-methoxyphenyl)thiazol-3(2H)-
yl]propanoic acid (4e): White powder, yield: 0.36 g (94%); mp 202–
203 8C; IR (KBr, cmÀ1):
n
max 3300–2800 (CO2H), 1738, 1650, 1614,
1220, 1107. 1H NMR (300 MHz, CDCl3):
d
1.37 (t, 3J = 7.0 Hz, CH3),
1370, 1152. 1H NMR (300 MHz, CDCl3): 1.80 (d, 3J = 6.6 Hz, CH3),
d
4.34 (q, 3J = 7.0 Hz, CH2), 5.62 (s, CH2), 7.44 (t, 3J = 7.1 Hz, 2 CH),
7.50 (t, 3J = 7.1 Hz, CH), 7.65 (s, CH), 8.30 (d, 3J = 7.1 Hz, 2 CH), 11.29
3.90 (s, CH3), 4.92 (q, 3J = 6.6 Hz, CH), 6.60 (s, CH), 7.03 (d,
3J = 8.1 Hz, 2 CH), 7.35 (d, 3J = 8.1 Hz, 2 CH), 7.40–7.49 (m, 3 CH),
8.22 (d, 3J = 7.4 Hz, 2 CH), 10.98 (s, COOH). 13C NMR (75 MHz,
(s, COOH). 13C NMR (75 MHz, CDCl3):
d 14.7 (Me), 49.2 (CH2), 62.4
(OCH2), 121.1 (CH), 128.8 (2 CH), 129.0 (CH), 129.7 (2 CH), 132.6
(C), 136.8 (C), 158.8 (C55N), 169.4 (C55O), 169.7 (C55O), 174.1
(C55O). MS: m/z (%) 334 (M+, 7), 276 (52), 261 (23), 105 (100), 77
(34), 45 (47). Anal. Calcd. for C15H14N2O5S (334.35): C, 53.88; H,
4.22; N, 8.38; Found: C, 53.6; H, 4.3; N, 8.5.
CDCl3):d 15.5 (Me), 55.9 (OMe), 57.7 (CH), 107.6 (CH), 115.1 (2 CH),
122.0 (C), 128.6 (2 CH), 129.6 (2 CH), 131.2 (2 CH), 132.3 (CH),
136.3 (C), 139.4 (C), 161.4 (C–OMe), 168.1 (C55N), 173.2 (C55O),
173.7 (C55O). MS: m/z (%) 382 (M+, 3), 310 (45), 105 (100), 77 (31),
73 (48), 45 (18). Anal. Calcd. for C20H18N2O4S (382.43): C, 62.81; H,
4.74; N, 7.33. Found: C, 62.4; H, 4.8; N, 7.5.
2-[2-(Benzoylimino)-4-(4-methoxyphenyl)thiazol-3(2H)-yl]a-
cetic acid (4b): Pale yellow crystals, yield: 0.29 g (79%); mp 200–
2-[2-(Benzoylimino)-4-(4-bromophenyl)thiazol-3(2H)-yl]pro-
panoic acid (4f): Pale yellow crystals, yield: 0.33 g (85%); mp 223–
202 8C; IR (KBr, cmÀ1):
n
max 3250–2700 (CO2H), 1741, 1680, 1609,
1365, 1102. 1H NMR (300 MHz, CDCl3):
d
3.81 (s, OMe), 4.82 (s,
224 8C; [a
]D = - 43.5; IR (KBr, cmÀ1): nmax 3400–2900 (CO2H),
CH2), 6.98 (s, CH), 7.08 (d, 3J = 8.7 Hz, 2 CH), 7.40 (d, 3J = 8.7 Hz, 2
CH), 7.45–7.54 (m, 3 CH), 8.19 (d, 3J = 7.0 Hz, 2 CH), 11.12 (s,
COOH). 13C NMR (75 MHz, CDCl3):
1739, 1700, 1592, 1381, 1203. 1H NMR (300 MHz, CDCl3):
d 1.68 (d,
3J = 6.9 Hz, CH3), 4.70 (q, 3J = 6.9 Hz, CH), 6.56 (s, CH), 7.27–7.41 (m,
3 CH), 7.34 (d, 3J = 8.1 Hz, 2 CH), 7.59 (d, 3J = 8.1 Hz, 2 CH), 8.18 (d,
d 49.2 (CH2), 56.2 (OMe), 107.3
(CH), 115.3 (2 CH), 122.6 (C), 129.1 (2 CH), 129.6 (2 CH), 131.5 (CH),
132.5 (2 CH), 137.3 (C), 139.4 (C), 161.1 (C), 168.9 (C55N), 169.7
(C55O), 173.4 (C55O). MS: m/z (%) 368 (M+, 2), 310 (35), 105 (100),
77 (28), 59 (28), 45 (19). Anal. Calcd. for C19H16N2O4S (368.41): C,
61.94; H, 4.38; N, 7.60. Found: C, 61.7; H, 4.5; N, 7.5.
3J = 7.2 Hz, 2 CH), 11.56 (s, COOH). 13C NMR (75 MHz, CDCl3):
d 15.6
(Me), 56.8 (CH), 108.9 (CH), 124.3 (C), 129.0 (2 CH), 129.7 (2 CH),
130.0 (C), 132.3 (2 CH), 132.6 (C), 133.0 (2 CH), 137.4 (C), 138.4 (C),
167.7 (C55N), 171.3 (C55O), 173.2 (C55O). MS: m/z (%) 432 (M++2, 1),
430 (M+, 1), 358 (31), 360 (31), 321 (12), 323 (12), 105 (100),
77 (29). Anal. Calcd. for C19H15BrN2O3S (431.30): C, 52.91; H, 3.51;
N, 6.50. Found: C, 53.2; H, 3.6; N, 6.6.
2-[4-(Ethoxycarbonyl)-2-(benzoylimino)thiazol-3(2H)-yl]-3-
methylbutanoic acid (4g): Cream powder, yield: 0.34 g (92%); mp
183–184 8C; IR (KBr, cmÀ1): nmax 3500–2900 (CO2H), 1750, 1720,
2-[2-(Benzoylimino)-4-(4-bromophenyl)thiazol-3(2H)-yl]ace-
tic acid (4c): Pale yellow crystals, yield: 0.36 g (86%); mp 211–
212 8C; IR (KBr, cmÀ1):
n
max 3320–2800 (CO2H), 1733, 1747, 1554,
4.78 (s, CH2), 6.56 (s, CH),
1343, 1178. 1H NMR (300 MHz, CDCl3):
d
7.28 (d, 3J = 7.2 Hz, 2 CH), 7.38 (t, 3J = 8.0 Hz, 2 CH), 7.46 (t,
3J = 8.0 Hz, CH), 7.56 (d, 3J = 8.0 Hz, 2 CH), 8.27 (d, 3J = 7.2 Hz, 2 CH),
11.06 (s, COOH). 13C NMR (75 MHz, CDCl3):
1670, 1601, 1235, 1100. 1H NMR (300 MHz, CDCl3):
d 0.69 (d,
d
50.1 (CH2), 107.6
3J = 6.5 Hz, CH3), 1.33 (d, 3J = 6.5 Hz, CH3), 1.42 (t, 3J = 7.0 Hz, CH3),
3.22 (m, CH), 4.40 (q, 3J = 7.0 Hz, CH2), 6.06 (d, 3J = 9.3 Hz, CH), 7.48
(t, 3J = 7.2 Hz, 2 CH), 7.53 (t, 3J = 7.2 Hz, CH), 7.72 (s, CH), 8.19 (d,
(CH), 127.7 (C), 128.5 (CH), 128.8 (2 CH), 129.7 (2 CH), 131.4 (2 CH),
132.2 (C), 132.8 (2 CH), 136.8 (C), 138.7 (C), 155.6 (C55N), 169.5
(C55O), 174.4 (C55O). MS: m/z (%) 418 (M++2, 1.2), 416 (M+, 1.2), 360
(34), 358 (34), 323 (10), 321 (10), 105 (100), 77 (36). Anal. Calcd. for
3J = 7.2 Hz, 2 CH), 11.09 (s, COOH). 13C NMR (75 MHz, CDCl3):
d 14.5
(Me), 19.3 (Me), 21.7 (Me), 28.1 (CH), 62.8 (OCH2), 66.8 (CH), 121.6
(CH), 128.7 (2 CH), 129.0 (CH), 129.7 (2 CH), 132.7 (C), 135.8 (C),
158.9 (C55N), 164.8 (C55O), 172.4 (C55O), 174.3 (C55O). MS: m/z (%)
376 (M+, 4), 303 (29), 276 (59), 105 (100), 77 (38), 45 (67). Anal.
Calcd. for C18H20N2O5S (376.43): C, 57.43; H, 5.36; N, 7.44. Found:
C, 57.7; H, 5.2; N, 7.6.
2-[2-(Benzoylimino)-4-(4-methoxyphenyl)thiazol-3(2H)-yl]-
3-methylbutanoic acid (4h): White powder, yield: 0.36 g (89%);
mp 169–171 8C; IR (KBr, cmÀ1): nmax 3300–2750 (CO2H), 1742,
C
18H13BrN2O3S (417.28): C, 51.81; H, 3.14; N, 6.71. Found: C, 51.3;
H, 3.3; N, 6.8.
2-[4-(Ethoxycarbonyl)-2-(benzoylimino)thiazol-3(2H)-yl]pro-
panoic acid (4d): Cream powder, yield: 0.33 g (96%); mp 175–
177 8C; IR (KBr, cmÀ1):
n
max 3600–3000 (CO2H), 1749, 1716, 1650,
1.39 (t, 3J = 7.2 Hz,
1605, 1203, 1106. 1H NMR (300 MHz, CDCl3):
d
CH3), 1.85 (d, 3J = 6.9 Hz, CH3), 4.34 (q, 3J = 7.2 Hz, CH2), 6.42 (q,
3J = 6.9 Hz, CH), 7.42 (t, 3J = 7.5 Hz, 2 CH), 7.50 (t, 3J = 7.5 Hz, CH),

A.S. Shahvelayati et al. / Chinese Chemical Letters 25 (2014) 119–122
121
1664, 1609, 1378, 1162. 1H NMR (300 MHz, CDCl3):
d
0.51
1742, 1673, 1612, 1375, 1163. 1H NMR (300 MHz, CDCl3):
d
1.67 (d,
(d, 3J = 6.6 Hz, CH3), 1.05 (d, 3J = 6.6 Hz, CH3), 3.25 (m, CH), 3.89
(s, CH3), 4.46 (d, 3J = 10.5 Hz, CH), 6.64 (s, CH), 7.04 (d, 3J = 8.7 Hz, 2
CH), 7.35 (d, 3J = 8.7 Hz, 2 CH), 7.48 (t, 3J = 8.3 Hz, 2 CH), 7.54 (t,
3J = 8.3 Hz, CH), 8.17 (d, 3J = 8.3 Hz, 2 CH), 10.89 (s, COOH). 13C NMR
3J = 6.8 Hz, CH3), 2.37 (s, CH3), 3.83 (s, CH3), 4.81 (q, 3J = 6.8 Hz, CH),
6.94 (s, CH), 7.12 (d, 3J = 8.6 Hz, 2 CH), 7.27 (d, 3J = 8.1 Hz, 2 CH),
7.43 (d, 3J = 8.6 Hz, 2 CH), 8.06 (d, 3J = 8.1 Hz, 2 CH), 10.85 (s,
COOH). 13C NMR (75 MHz, CDCl3):
d 15.5 (Me), 22.0 (Me), 56.2
(75 MHz, CDCl3):
d
19.3 (Me), 20.15 (Me), 27.7 (CH), 55.8 (OMe),
(OMe), 60.6 (CH), 107.5 (CH), 115.4 (2 CH), 122.8 (C), 129.6 (2 CH),
129.8 (2 CH), 131.7 (2 CH), 134.9 (CH), 139.3 (C), 142.5 (C), 161.2
(C–OMe), 167.3 (C55N), 171.4 (C55O), 173.2 (C55O). MS: m/z (%) 396
(M+, 3), 324 (33), 119 (100), 91 (42), 73 (47), 45 (20). Anal. Calcd. for
71.9 (CH), 108.0 (CH), 115.2 (2 CH), 121.8 (C), 129.0 (2 CH), 129.3 (2
CH), 131.6 (2 CH), 132.8 (CH), 135.5 (C), 142.0 (C), 161.4 (C–OMe),
169.1 (C55N), 170.5 (C55O), 172.8 (C55O). MS: m/z (%) 410 (M+, 2),
310 (39), 105 (100), 101 (19), 77 (38), 45 (15). Anal. Calcd. for
C
21H20N2O4S (396.46): C, 63.62; H, 5.08; N, 7.07. Found: C, 63.2; H,
4.9; N, 6.9.
2-[2-(4-Methylbenzoylimino)-4-(4-bromophenyl)thiazol-
C
22H22N2O4S (410.49): C, 64.37; H, 5.40; N, 6.82. Found: C, 64.7; H,
5.5; N, 7.0.
2-[2-(Benzoylimino)-4-(4-bromophenyl)thiazol-3(2H)-yl]-3-
3(2H)-yl]propanoic acid (4l): Pale yellow crystals, yield: 0.37 g
methylbutanoic acid (4i): Pale yellow crystals, yield: 0.44 g (96%);
mp 171–173 8C; IR (KBr, cmÀ1): nmax 3400–2900 (CO2H), 1739,
(83%); mp 186–188 8C; [
a
]
D = À28.6; IR (KBr, cmÀ1): nmax 3430–
2950 (CO2H), 1743, 1710, 1605, 1376, 1213. 1H NMR (300 MHz,
1700, 1592, 1381, 1203. 1H NMR (300 MHz, CDCl3):
d
0.53 (d,
CDCl3): d
1.67 (d, 3J = 6.8 Hz, CH3), 2.37 (s, CH3), 4.84 (q, 3J = 6.8 Hz,
3J = 6.6 Hz, CH3), 1.08 (d, 3J = 6.6 Hz, CH3), 3.28 (m, CH), 4.38 (d,
3J = 9.0 Hz, CH), 6.75 (s, CH), 7.32 (d, 3J = 8.1 Hz, 2 CH), 7.49 (t,
3J = 7.5 Hz, 2 CH), 7.53 (t, 3J = 7.5 Hz, CH), 7.71 (d, 3J = 8.1 Hz, 2 CH),
8.18 (d, 3J = 7.5 Hz, 2 CH), 11.08 (s, COOH). 13C NMR (75 MHz,
CH), 7.06 (s, CH), 7.27 (d, 3J = 8.0 Hz, 2 CH), 7.45 (d, 3J = 8.4 Hz, 2
CH), 7.77 (d, J = 8.4 Hz, 2 CH), 8.05 (d, 3J = 8.0 Hz, 2 CH), 10.92 (s,
COOH). 13C-NMR (75 MHz, CDCl3):
d 15.6 (Me), 22.0 (Me), 56.7
(CH), 108.8 (CH), 124.3 (2 CH), 129.7 (C), 129.8 (2 CH), 130.0 (2 CH),
132.3 (C), 133.0 (2 CH), 134.3 (C), 138.3 (C), 142.6 (C), 167.5 (C55N),
171.3 (C55O), 173.3 (C55O). MS: m/z (%) 446 (M++2, 1.5), 444 (M+,
1.4), 374 (29), 372 (29), 119 (100), 91 (49). Anal. Calcd. for
CDCl3):d 19.4 (Me), 19.9 (Me), 27.6 (CH), 72.6 (CH), 109.3 (CH),
125.5 (C), 128.7 (C), 129.1 (2 CH), 129.3 (2 CH), 131.5 (2 CH), 133.0
(2 CH), 133.1 (CH), 135.2 (C), 141.0 (C), 169.5 (C55N), 169.9 (C55O),
172.9 (C55O). MS: m/z (%) 460 (M++2, 1), 458 (M+, 2), 360 (26), 358
(24), 323 (10), 321 (10), 105 (100), 77 (33). Anal. Calcd. for
C20H17N2O3S (445.33): C, 53.94; H, 3.85; N, 6.29. Found: C, 54.3; H,
3.9; N, 6.4.
C21H19BrN2O3S (459.36): C, 54.91; H, 4.17; N, 6.10. Found: C, 54.5;
H, 4.1; N, 6.2.
3. Results and discussion
2-[4-(Ethoxycarbonyl)-2-(4-methylbenzoylimino)thiazol-
3(2H)-yl]propanoic acid (4j): Cream crystals, yield: 0.29 g (80%);
mp 165–167 8C; IR (KBr, cmÀ1): nmax 3650–3000 (CO2H), 1752,
The structures of compounds 4a–l were assigned based on their
IR, 1H NMR, 13C NMR spectral data [14]. For example, the 1H NMR
1720, 1660, 1610, 1250, 1105; 1H NMR (300 MHz, CDCl3):
d
1.38 (t,
spectrum of 4a exhibited three singlets for CH2N (d 5.62), CHS (d
3J = 7.1 Hz, CH3), 1.83 (d, 3J = 6.8 Hz, CH3), 2.40 (s, CH3), 4.33 (q,
3J = 7.1 Hz, CH2), 6.40 (q, 3J = 6.8 Hz, CH), 7.19 (d, 3J = 7.9 Hz, 2 CH),
7.63 (s, CH), 8.10 (d, 3J = 7.9 Hz, 2 CH), 11.17 (s, COOH); 13C NMR
7.65), and CO2H (d 11.29) protons, along with characteristic signals
for the ethyl and phenyl groups. In the 13C NMR spectrum, the
signals corresponding to the carbonyl groups of 4a were observed
(75 MHz, CDCl3):
d
14.5 (Me), 15.6 (Me), 22.1 (Me), 56.3 (CH), 62.6
at d 169.4, 169.7, and 174.1, while the C55N appeared at d 158.8. The
(OCH2), 121.5 (CH), 128.0 (C), 129.3 (2 CH), 129.9 (2 CH), 133.6 (C),
143.0 (C), 158.9 (C55N), 168.0 (C55O), 174.8 (C55O), 174.9 (C55O).
MS: m/z (%) 362 (M+, 12), 290 (68), 119 (100), 91 (56), 73 (24), 45
(50). Anal. Calcd. for C17H18N2O5S (362.40): C, 56.34; H, 5.01; N,
7.73. Found: C, 56.7; H, 4.9; N, 7.8.
2-[2-(4-Methylbenzoylimino)-4-(4-methoxyphenyl)thiazol-
3(2H)-yl]propanoic acid (4k): Colorless crystals, yield: 0.33 g
(85%); mp 197–198 8C; IR (KBr, cmÀ1): nmax 3330–2700 (CO2H),
mass spectrum of 4a displayed the molecular ion peak at m/z 334.
The 1H NMR and 13C NMR spectra of 4b–l were similar to those for
4a except for the alkyl and aryl moieties, which exhibited
characteristic resonances in appropriate regions of the spectrum.
The recyclability of ionic liquid [bmim]Br was examined in
synthesis of thiazole-2(3H)-imine 4d. It was recovered from
the reaction mixture by extraction with water. After evaporation of
the water under reduced pressure, it was reused three times for the
O
Br
O
S
R
O
R'
CO H
2
S
3
C
Ar
N
H
N
H
CO H
2
+
Ar
N
R
NH
2
5
O
R
O
R
O
R
R'
HO
O
R'
OH
N
OH
HN
OH
N
R'
-H O
2
N
N
S
N
S
S
Ar
O
Ar
O
Ar
O
6
7
4
Scheme 2. Proposed mechanism for the formation of compounds 4.

122
A.S. Shahvelayati et al. / Chinese Chemical Letters 25 (2014) 119–122
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synthesis of 4d. In the second run, 4d was obtained in 90% yield,
and that reduced to 88% in the third run.
Although the mechanistic details of the reaction are not known,
a plausible rationalization may be advanced to explain the product
formation (Scheme 2) [9]. Presumably, the reaction starts with
the formation of thiourea derivative 5, followed by its alkylation by
3 to generate intermediate 6. This intermediate undergoes a
cyclization reaction to afford 7, which is converted to product 4 by
elimination of H2O.
In order to confirm that the chiral center present in the amino
acid component 3 remains intact under the reaction conditions, we
measured the optical activities of compounds 4f and 4l, obtained
from S-(+)-alanine, for solutions containing about 1 g of the
samples in 5 mL of dimethylformamide. The specific rotation for
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2(3H)-imine-linked glycoconjugates, Synthesis 13 (2008) 1994–1996.
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4f and 4l were [
we conclude that the configurations of the amino acid components
remain unchanged in these reactions.
a
]
D = À43.5 and [
a
]
D = À28.6, respectively. Thus,
4. Conclusion
In conclusion, we have developed a convenient, one-pot
method for the synthesis of functionalized thiazol-2(3H)-imines
using aroylisothiocyanates and a-amino acids in the presence of a-
bromoketones in an ionic liquid. The present method may be
considered as a practical route for the synthesis of thiazole-ring
systems.
[12] M.A. Martins, C.P. Frizzo, D.N. Moreira, N. Zanatta, H.G. Bonacorso, Ionic liquids in
heterocyclic synthesis, Chem. Rev. 108 (2008) 2015–2050.
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alkylation of amino-9,10-anthraquinones by trialkyl phosphites, Tetrahedron
Lett. 48 (2007) 3753–3756.
[14] I. Yavari, S. Souri, Efficient synthesis of functionalized 2-pyridones from malonyl
dichloride, alkylamines and dimethyl acetylenedicarboxylate, Synlett 19 (2007)
2969–2970.
Acknowledgment
[15] I. Yavari, M. Sabbaghan, K. Porshamsian, et al., Efficient synthesis of alkyl 2-[2-
(arylcarbonylimino)-3-aryl-4-oxo-1,3-thiazolan-5-ylidene]-acetates, Mol. Di-
vers. 11 (2007) 81–85.
[16] I. Yavari, A.S. Shahvelayati, A. Malekafzali, Efficient synthesis of functionalized
2,4-diaminothiazoles from tetramethylguanidine, isothiocyanates, and a-bromo-
ketones, J. Sulfur Chem. 31 (2010) 499–508.
We are grateful to Dr. Mina Ghiasi, Az-Zahra University, Tehran,
Iran, for polarimetric measurements.
[17] I. Yavari, S. Nasiri-Gheidari, A. Mirzaei, Isoquinoline-mediated S-vinylation and N-
vinylation of benzo[d]oxazole-2-thiol and benzo[d]thiazole-2-thiol, Chin. Chem.
Lett. 23 (2012) 5–8.
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