Facile one-pot procedure for the synthesis of 2-aminothiazole derivatives

Article abstract of DOI:10.3987/COM-12-12510

A facile, efficient synthesis of 2-aminothiazole derivatives by the reaction of easily available aromatic methyl ketones with thiourea/N-substituted thioureas in the presence of copper(II) bromide was developed. The reaction underwent a one-pot ?-bromination/cyclization process.

Full text of DOI:10.3987/COM-12-12510

HETEROCYCLES, Vol. 85, No. 8, 2012
1941
HETEROCYCLES, Vol. 85, No. 8, 2012, pp. 1941 - 1948. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 17th May, 2012, Accepted, 14th June, 2012, Published online, 22nd June, 2012
DOI: 10.3987/COM-12-12510
FACILE ONE-POT PROCEDURE FOR THE SYNTHESIS OF
2-AMINOTHIAZOLE DERIVATIVES
Guodong Yin,* Junrui Ma, Houqiang Shi, and Qing Tao
Hubei Key Laboratory of Pollutant Analysis and Reuse Technology, College of
Chemistry and Environmental Engineering, Hubei Normal University, Huangshi
435002, People’s Republic of China. E-mail: gdyin@hbnu.edu.cn
Abstract – A facile, efficient synthesis of 2-aminothiazole derivatives by the
reaction of easily available aromatic methyl ketones with thiourea/N-substituted
thioureas in the presence of copper(II) bromide was developed. The reaction
underwent a one-pot α-bromination/cyclization process.
INTRODUCTION
Thiazole derivatives are present in many natural and synthetic products with a wide range of
pharmacological activities, such as anticancer, antiviral, antibacterial, antifungal, and anti-inflammatory
activities.1–3 Among them, aminothiazole derivatives possess an antitumor activity through the inhibition
of the kinases.4,5 Aminothiazoles are also known to be ligands of estrogen receptors6 as well as a novel
class of adenosine receptor antagonists.7 In view of their importance, a variety of approaches to
2-aminothiazole derivatives have been reported. Hantzsch thiazole synthesis, involving the reaction of
α-halo carbonyl compounds and thioureas, is still one of the most widely used methods.8–13
In recent years, much attention has been paid to one-pot synthesis,14 which is a strategy to improve the
efficiency of a chemical reaction because of avoiding a separation process and purification of the
intermediates. However, most of synthetic strategies towards the one-pot preparation of 2-aminothiazole
underwent α-iodo ketones15,16 or α-tosyloxy ketones17–21 intermediates. In addition, although there are
numerous efficient methods for α-bromination carbonyl compounds,22–28 few reports foucs on the one-pot
α-bromination/cyclization process for 2-aminothiazole.29 Copper(II) bromide was found to be an efficient,
simple and inexpensive reagent for the α-bromination of carbonyl compounds.30,31 Based on the
above-motioned results, we herein reported a facile, efficient one-pot synthesis of 2-aminothiazole
derivatives via α-bromination/cyclization process from easily available aromatic methyl ketones.
RESULTS AND DISCUSSION

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HETEROCYCLES, Vol. 85, No. 8, 2012
Scheme 1
Table 1. Optimization of reaction condition for the synthesis of 3a in the presence of K2CO3
Entry Solvent Temp (oC) Yielda (%) Entry Solvent Temp (oC) Yielda (%)
1
2
3
4
5
EtOAc
MeOH
EtOH
THF
reflux
reflux
reflux
reflux
reflux
87
80
82
25
40
6
7
CHCl3
H2O
reflux
60
0
0
8
EtOAc
EtOAc
EtOAc
20
0
9
reflux
reflux
45b
30c
MeCN
10
aIsolated yield based on acetophenone. bNaHCO3 as a base. cno base was used.
In our initial experiments, acetophenone (1a) was used as the model substrate to react with thiourea in
different solvents (such as MeOH, EtOH, THF, MeCN, CHCl3, H2O and EtOAc) in the presence of
copper(II) bromide and K2CO3 for the preparation of the expected 4-phenylthiazol-2-amine (3a) (Scheme
1). As shown in Table 1, it can be seen that the reaction gave the highest yield (87%) in refluxing EtOAc
(entry 1). 3a was also obtained in good yield in MeOH or EtOH (entries 2, 3). However, the reaction gave
poor yields in THF and MeCN (entries 4, 5). No reaction occurred in CHCl3, water or in EtOAc at room
temperature (entries 6–8). When NaHCO3 or no base was employed, 3a was isolated only in 45% and
1
30% yields respectively (entries 9, 10). Its structure was assigned on the basis of H NMR and mass
1
spectra. The H NMR spectra of 3a shows a characteristic peak at 6.73 ppm corresponding to the
hydrogen of thiazole ring, which are in accordance with the literature.21
After the optimization of reaction conditions, we next examined the scope and generality of this method
to other substrates using different aromatic ketones and N-substituted thioureas (Scheme 2). The results
are summarized in Table 2. The condensation of different methyl ketones including electron-donating or
electron-withdrawing groups (such as -OMe, -OBn, -F and C6H5) on the 4-position of phenyl ring with
thiourea gave the expected products 4-aryl-2-aminothiazole 3b–e in good to excellent yields (78–90%,
entries 2–5). 2-Acetylnaphthalene also gave the 4-(naphthalen-2-yl)thiazol-2-amine (3f) in 82% yield
(entry 6). Furthermore, we were pleased to find that N-substituted thioureas such as N-methylthiourea,
N-allylthiourea, N-phenylthiourea and N-(naphthalen-2-yl)thiourea reacted with aryl or heteroaryl methyl
ketones afforded the 2-aminothiazole derivatives 3g–u in good yields (68–88%, entries 7–21). Notably,
the reaction of 4'-fluoroacetophenone with N-phenylthiourea and N-(naphthalen-2-yl)thiourea delivered
4-(4-fluorophenyl)-N-phenylthiazol-2-amine (3s) and 4-(4-fluorophenyl)-N-(naphthalen-2-yl)thiazol-2-

HETEROCYCLES, Vol. 85, No. 8, 2012
1943
amine (3u) in 70% and 68% isolated yields respectively. The slightly lower yields might be attributed to
the steric hindrance of N-aryl substituted thioureas and electron-withdrawing property of fluorine atom.
However, no expected product was isolated using cyclohexanone as a substrate (entry 22).
Scheme 2
Table 2. Synthesis of 2-aminothiazole derivatives 3
Entry
R1
C6H5
R2
H
Yield of 3 (%)a Entry
R1
4-FC6H4
4-C6H5C6H4
2-Naph
R2
Yield of 3 (%)a
3l (70)
1
2
3a (87)
3b (90)
3c (89)
3d (78)
3e (85)
3f (82)
3g (85)
3h (80)
3i (75)
3j (85)
12
13
14
15
16
17
18
19
20
21
Allyl
Allyl
Allyl
Allyl
4-MeOC6H4
4-BnOC6H4
4-FC6H4
4-C6H5C6H4
2-Naph
H
3m (86)
3n (81)
3o (83)
3p (85)
3q (80)
3r (84)
3
H
4
H
2-Furyl
5
H
2-Thienyl
C6H5
Allyl
C6H5
6
H
7
C6H5
CH3
CH3
CH3
Allyl
4-MeOC6H4
4-FC6H4
C6H5
C6H5
C6H5
8
2-Furyl
3s (70)
9
2-Thienyl
C6H5
2-Naph
2-Naph
3t (79)
10
4-FC6H4
3u (68)
b
—
11
4-MeOC6H4
3k (88)
22
Cyclohexanone
Allyl
aIsolated yield based on aromatic methyl ketones. bNo expected product was obtained.
EXPERIMENTAL
All reagents were purchased from commercial suppliers and used without further purification. All
1
solvents were of analytical grade and dried according to published methods and distilled before use. H
13
and C NMR spectra were recorded on a Bruker AV 300 spectrometers using CDCl3 as the solvent.
Chemical shifts are reported relative to TMS (internal standard). Mass spectra were measured on a LCQ
Advantage MAX (ESI). IR spectra were obtained as KBr pellet samples on a Nicolet 5700 FTIR
spectrometer. The elemental analysis was performed by Perkin Elmer 2400. Melting points were
determined on a X-4 micromelting apparatus and are uncorrected.
General procedure for the synthesis of 2-aminothiazole derivatives 3
To a solution of aromatic ketones (1.0 mmol) in EtOAc (15 mL) was added CuBr2 (447 mg, 2.0 mmol)
and the reaction mixture was allowed to reflux for 3–6 h until the starting material disappeared (detected

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HETEROCYCLES, Vol. 85, No. 8, 2012
1
by TLC or crude H NMR). Then thiourea/N-substituted thioureas (2.0 mmol) and potassium carbonate
(276 mg, 2.0 mmol) was added to the mixture and heating was continued for another 5 h. After the
reaction was completed, 20 mL water was added and extracted with another 30 mL EtOAc (two times).
The organic layer was combined and dried over anhydrous MgSO4, filtered, concentrated, and the residue
was purified by flash chromatography on silica gel using EtOAc/petroleum ether as eluent to give 3.
o
o
4-Phenylthiazol-2-amine (3a): Mp 149–150 C (lit.,12 150–151 C). IR (KBr) (νmax, cm-1): 3433, 3256,
1
1598, 1522, 1336, 1034, 712. H NMR (300 MHz, CDCl3): δ (ppm) 7.76–7.74 (m, 2H), 7.41–7.29 (m,
3H), 6.73 (s, 1H), 5.14 (s, 2H, NH2). ESI-MS: m/z 175.73 [M+H]+.
o
4-(4-Methoxyphenyl)thiazol-2-amine (3b): Mp 206–207 oC (lit.,12 206–207 C). IR (KBr) (νmax, cm-1):
3436, 3271, 1624, 1528, 1245, 1175. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.70 (d, 2H, J=8.7 Hz), 6.92
(d, 2H, J=8.7 Hz), 6.58 (s, 1H), 5.30 (s, 2H, NH2), 3.83 (s, 3H). ESI-MS: m/z 206.14 [M+H]+.
4-(4-(Benzyloxy)phenyl)thiazol-2-amine (3c): Mp 162–163 oC. IR (KBr) (νmax, cm-1): 3419, 3110, 1604,
1
1493, 1239, 1034. H NMR (300 MHz, CDCl3) δH: 7.70 (d, 2H, J=8.7 Hz), 7.46–7.32 (m, 5H), 6.98 (d,
2H, J=8.7 Hz), 6.59 (s, 1H), 5.09 (s, 2H), 5.01 (s, 2H, NH2). 13C NMR (75 MHz, CDCl3) δC: 167.1, 158.4,
151.0, 136.9, 128.6, 128.0, 127.8, 127.5, 127.3, 114.9, 101.1, 70.0. ESI-MS: m/z 282.47 [M+H]+. Anal.
Calcd for C16H14N2OS: C, 68.06; H, 5.00; N, 9.92; Found: C, 68.01; H, 5.04; N, 9.96.
o
4-(4-Fluorophenyl)thiazol-2-amine (3d): Mp 103–104 oC (lit.,12 102–103 C). IR (KBr) (νmax, cm-1):
1
3450, 3285, 3114, 1630, 1528, 1484, 1336. H NMR (300 MHz, CDCl3): δ (ppm) 7.75–7.70 (m, 2H),
7.10–7.03 (m, 2H), 6.65 (s, 1H), 5.15 (s, 2H, NH2). 13C NMR (75 MHz, CDCl3) δC: 167.8, 162.6 (d,
4
3
2
1JC-F=245.3 Hz), 150.2, 130.9 (d, JC-F=3.3 Hz), 127.7 (d, JC-F=8.0 Hz), 115.6 (d, JC-F=21.5 Hz), 102.1.
ESI-MS: m/z 194.09 [M+H]+.
4-(Biphenyl-4-yl)thiazol-2-amine (3e)16: Mp 202–203 oC. IR (KBr) (νmax, cm-1): 3434, 3258, 1602, 1524,
1
1317, 1034, 751, 709. H NMR (300 MHz, CDCl3): δ (ppm) 7.87–7.83 (m, 2H), 7.65–7.61 (m, 4H),
7.48–7.32 (m, 3H), 6.78 (s, 1H), 5.06 (s, 2H, NH2). 13C NMR (75 MHz, CDCl3) δC: 167.2, 150.8, 140.7,
140.5, 133.5, 128.8, 127.3, 127.0, 126.4, 102.9. ESI-MS: m/z 253.06 [M+H]+.
o
4-(Naphthalen-2-yl)thiazol-2-amine (3f): Mp 150–151 oC (lit.,13 153–154 C). IR (KBr) (νmax, cm-1):
1
3432, 3258, 1602, 1524, 1317. H NMR (300 MHz, CDCl3): δ (ppm) 8.31 (s, 1H), 7.90–7.80 (m, 4H),
7.50–7.43 (m, 2H), 6.86 (s, 1H), 5.21 (s, 2H, NH2). 13C NMR (75 MHz, CDCl3) δC: 167.3, 151.2, 133.6,
133.0, 131.8, 128.3, 128.2, 127.6, 126.2, 125.9, 125.0, 123.9, 103.4. ESI-MS: m/z 226.60 [M+H]+.
o
N-Methyl-4-phenylthiazol-2-amine (3g): Mp 125–126 oC (lit.,13 136–137 C). IR (KBr) (νmax, cm-1):
3447, 3209, 1596, 1449, 1398, 1329. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.81–7.78 (m, 2H), 7.41-7.31
(m, 3H), 6.71 (s, 1H), 5.74 (s, 1H, NH), 2.99 (d, 3H, J=4.2 Hz, CH3). 13C NMR (75 MHz, CDCl3)
δC:171.6, 151.6, 135.1, 128.4, 127.6, 126.0, 100.3, 32.1. ESI-MS: m/z 190.71 [M+H]+.
N-Methyl-4-(furan-2-yl)thiazol-2-amine (3h): Mp 103–104 oC. IR (KBr) (νmax, cm-1): 3207, 3117, 1572,

HETEROCYCLES, Vol. 85, No. 8, 2012
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1
1449. H NMR (300 MHz, CDCl3) δH: 7.40 (dd, 1H, J1=1.8 Hz, J2=0.6 Hz), 6.68 (s, 1H), 6.63 (dd, 1H,
J1=3.3 Hz, J2=0.6 Hz), 6.44 (dd, 1H, J1=3.3 Hz, J2=1.8 Hz), 5.86 (s, 1H, NH), 3.00 (d, 3H, J=4.2 Hz). 13C
NMR (75 MHz, CDCl3) δC: 172.0, 150.5, 143.0, 141.7, 111.3, 106.1, 100.0, 32.4. ESI-MS: m/z 180.71
[M+H]+. Anal. Calcd for C8H8N2OS: C, 53.31; H, 4.47; N, 15.54; Found: C, 53.26; H, 4.51; N, 15.58.
o
N-Methyl-4-(thiophen-2-yl)thiazol-2-amine (3i)20: Mp 108–109 C. IR (KBr) (νmax, cm-1): 3450, 3213,
3104, 1588, 1399, 1287. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.33 (dd, 1H, J1=3.3 Hz, J2=1.2 Hz), 7.21
(dd, 1H, J1=5.4 Hz, J2=1.2 Hz), 7.02 (dd, 1H, J1=5.4 Hz, J2=3.3 Hz), 6.60 (s, 1H), 6.07 (s, 1H, NH), 2.96
13
(d, 3H, J=4.8 Hz). C NMR (75 MHz, CDCl3) δC: 171.5, 145.9, 138.9, 127.4, 124.3, 123.3, 99.3, 32.3.
ESI-MS: m/z 196.76 [M+H]+.
o
N-Allyl-4-phenylthiazol-2-amine (3j): Mp 72–73 oC (lit.,13 73 C). IR (KBr) (νmax, cm-1): 3449, 3194,
1
2966, 1581, 1416, 1321, 915, 702. H NMR (300 MHz, CDCl3): δ (ppm) 7.81–7.77 (m, 2H), 7.40–7.28
(m, 3H), 6.71 (s, 1H), 6.00–5.87 (m, 1H), 5.61 (s, 1H, NH), 5.37–5.30 (m, 1H), 5.24–5.19 (m, 1H), 3.9 (s,
13
2H). C NMR (75 MHz, CDCl3) δC: 170.1, 151.3, 134.9, 133.5, 128.4, 127.5, 126.0, 116.9, 100.6, 48.2.
ESI-MS: m/z 216.50 [M+H]+.
N-Allyl-4-(4-methoxyphenyl)thiazol-2-amine (3k): Mp 89–90 oC. IR (KBr) (νmax, cm-1): 3221, 2954,
1
1573, 1414, 1328, 1236, 1021. H NMR (300 MHz, CDCl3) δH: 7.72 (d, 2H, J=9.0 Hz), 6.90 (d, 2H,
J=9.0 Hz), 6.57 (s, 1H), 5.96–5.86 (m, 1H), 5.67 (s, 1H, NH), 5.36–5.29 (m, 1H), 5.22–5.18 (m, 1H), 3.91
13
(s, 2H), 3.83 (s, 3H). C NMR (75 MHz, CDCl3) δC: 170.0, 159.0, 150.9, 133.5, 127.8, 127.1, 116.7,
113.7, 98.7, 55.1, 48.1. ESI-MS: m/z 246.76 [M+H]+. Anal. Calcd for C13H14N2OS: C, 63.39; H, 5.73; N,
11.37; Found: C, 63.34; H, 5.80; N, 11.42.
N-Allyl-4-(4-fluorophenyl)thiazol-2-amine (3l): Mp 75–76 oC. IR (KBr) (νmax, cm-1): 3216, 3087, 2968,
1
2878, 1574, 1489, 1325, 1225. H NMR (300 MHz, CDCl3) δH: 7.77–7.73 (m, 2H), 7.08–7.03 (m, 2H),
6.63 (s, 1H), 6.00–5.87 (m, 1H), 5.57 (s, 1H, NH), 5.37–5.30 (m, 1H), 5.24–5.19 (m, 1H), 3.94 (s, 2H).
1
4
13C NMR (75 MHz, CDCl3) δC: 170.1, 162.3 (d, JC-F=245.1 Hz), 150.2, 133.3 (d, JC-F=3.2 Hz), 131.1,
127.6 (d, 3JC-F=8.0 Hz), 116.9, 115.2 (d, 2JC-F=21.4 Hz), 100.2, 48.2. ESI-MS: m/z 234.85 [M+H]+. Anal.
Calcd for C12H11FN2S: C, 61.52; H, 4.73; N, 11.96; Found: C, 61.47; H, 4.79; N, 12.04.
N-Allyl-4-(biphenyl-4-yl)thiazol-2-amine (3m): Mp 134–135 oC. IR (KBr) (νmax, cm-1): 3209, 3111,
2969, 2887, 1588, 1410, 1323, 1123. 1H NMR (300 MHz, CDCl3) δH: 7.86 (d, 2H, J=8.7 Hz), 7.64–7.60
(m, 4H), 7.47–7.41 (m, 2H), 7.37–7.31 (m, 1H), 6.75 (s, 1H), 6.00–5.88 (m, 1H), 5.70 (s, 1H, NH),
5.38–5.30 (m, 1H), 5.24–5.19 (m, 1H), 3.94 (s, 2H). 13C NMR (75 MHz, CDCl3) δC: 169.8, 151.0, 140.7,
140.2, 133.9, 133.5, 128.7, 127.2, 127.1, 126.9, 126.4, 117.1, 100.9, 48.4. ESI-MS: m/z 293.61 [M+H]+.
Anal. Calcd for C16H14N2OS: C, 68.06; H, 5.00; N, 9.92; Found: C, 68.01; H, 5.06; N, 9.98.
N-Allyl-4-(naphthalen-2-yl)thiazol-2-amine (3n): Mp 120–121 oC. IR (KBr) (νmax, cm-1): 3413, 3196,
1
3087, 2966, 1580, 1418, 1354, 1290, 1233. H NMR (300 MHz, CDCl3) δH: 8.33 (s, 1H), 7.90–7.80 (m,

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HETEROCYCLES, Vol. 85, No. 8, 2012
4H), 7.50–7.42 (m, 2H), 6.84 (s, 1H), 6.00–5.90 (m, 1H), 5.62 (s, 1H, NH), 5.40–5.21 (m, 2H), 3.98 (s,
2H). 13C NMR (75 MHz, CDCl3) δC: 169.8, 151.2, 133.6, 133.4, 132.9, 132.0, 128.3, 128.1, 127.6, 126.2,
125.8, 124.9, 124.0, 117.2, 101.5, 48.3. ESI-MS: m/z 266.90 [M+H]+. Anal. Calcd for C16H14N2S: C,
72.15; H, 5.30; N, 10.52; Found: C, 72.10; H, 5.36; N, 10.58.
o
N-Allyl-4-(furan-2-yl)thiazol-2-amine (3o): Mp 81–83 oC (lit.,17 104 C). IR (KBr) (νmax, cm-1): 3443,
1
3210, 3004, 1548, 1451, 1195, 1073, 1003, 935. H NMR (300 MHz, CDCl3): δ (ppm) 7.39 (dd, 1H,
J1=1.8 Hz, J2=0.6 Hz), 6.78 (s, 1H), 6.63 (dd, 1H, J1=3.3 Hz, J2=0.6 Hz), 6.43 (dd, 1H, J1=3.3 Hz, J2=1.8
Hz), 5.99–5.86 (m, 1H), 5.61 (s, 1H, NH), 5.37–5.30 (m, 1H), 5.24–5.19 (m, 1H), 3.93 (s, 2H); 13C NMR
(75 MHz, CDCl3): δ (ppm) 170.5, 150.5, 142.8, 141.7, 133.4, 117.1, 111.3, 106.2, 100.3, 48.4; IR (KBr)
3439, 3209, 3006, 1548, 1509, 1452, 1415, 1316, 1196, 1074, 1003 cm-1; ESI-MS: m/z 206.69 [M+H]+.
N-Allyl-4-(thiophen-2-yl)thiazol-2-amine (3p): Mp 49–50 oC. IR (KBr) (νmax, cm-1): 3410, 3214, 2968,
1
1542, 1580, 1415, 1356, 1294, 1220. H NMR (300 MHz, CDCl3) δH: 7.33 (dd, 1H, J1=3.6 Hz, J2=0.9
Hz), 7.20 (dd, 1H, J1=5.1 Hz, J2=0.9 Hz), 7.01 (dd, 1H, J1=5.1 Hz, J2=3.6 Hz), 6.59 (s, 1H), 5.98–5.84 (m,
1H), 5.64 (s, 1H, NH), 5.36–5.28 (m, 1H), 5.23–5.18 (m, 1H), 3.88 (s, 2H). 13C NMR (75 MHz, CDCl3)
δC: 170.0, 145.5, 138.8, 133.2, 127.4, 124.2, 123.3, 116.9, 99.5, 48.2. ESI-MS: m/z 222.70 [M+H]+. Anal.
Calcd for C10H10N2S2: C, 54.02; H, 4.53; N, 12.60; Found: C, 53.98; H, 4.56; N, 12.68.
o
N,4-Diphenylthiazol-2-amine (3q): Mp 137–138 oC (lit.,19 135–136 C). IR (KBr) (νmax, cm-1): 3448,
1
3228, 2951, 1605, 1583, 1467, 1423, 1310. H NMR (300 MHz, CDCl3): δ (ppm) 7.87–7.83 (m, 2H),
7.68 (s, 1H), 7.43–7.28 (m, 7H), 7.09–7.03 (m, 1H), 6.83 (s, 1H). 13C NMR (75 MHz, CDCl3) δC: 165.0,
151.2, 140.3, 134.5, 129.3, 128.6, 127.8, 126.1, 122.9, 118.3, 101.6. ESI-MS: m/z 252.82 [M+H]+.
o
4-(4-Methoxyphenyl)-N-phenylthiazol-2-amine (3r): Mp 139–141 oC (lit.,19 138–139 C). IR (KBr)
(νmax, cm-1): 3448, 3348, 1601, 1555, 1474, 1238, 743, 685. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.78 (d,
2H, J=9.0 Hz), 7.38–7.34 (m, 4H), 7.08–7.04 (m, 1H), 6.92 (d, 2H, J=9.0 Hz), 6.68 (s, 1H), 3.83 (s, 3H).
13C NMR (75 MHz, CDCl3) δC: 164.7, 159.4, 151.0, 140.4, 129.3, 127.5, 127.4, 122.8, 118.2, 113.9, 99.9,
55.2. ESI-MS: m/z 282.93 [M+H]+.
4-(4-Fluorophenyl)-N-phenylthiazol-2-amine (3s): Mp 132–133 oC (lit.,19 110–111 oC). IR (KBr) (νmax
,
1
cm-1): 3436, 1604, 1560, 1489, 1412, 1307, 1225, 837, 741, 688. H NMR (300 MHz, CDCl3): δ (ppm)
7.84–7.79 (m, 2H), 7.65 (s, 1H, NH), 7.37–7.34 (m, 4H), 7.10–7.04 (m, 3H), 6.75 (s, 1H). 13C NMR (75
MHz, CDCl3) δC: 165.3, 162.5 (d, 1JC-F=245.6 Hz), 150.2, 140.2, 130.7 (d, 4JC-F=3.2 Hz), 129.3, 127.8 (d,
3JC-F=8.1 Hz), 123.1, 118.4, 115.4 (d, 2JC-F=21.5 Hz), 101.1. ESI-MS: m/z 270.91 [M+H]+.
N-(Naphthalen-2-yl)-4-phenylthiazol-2-amine (3t): Mp 125–126 oC IR (KBr) (νmax, cm-1): 3393, 3182,
3119, 3055, 2932, 1591, 1552, 1502, 1338, 1278, 1173, 1068; 1H NMR (300 MHz, CDCl3) δH: 7.91–7.88
1
(m, 3H), 7.78–7.73 (m, 3H), 7.47–7.25 (m, 6H), 6.87 (s, 1H), NH not observed. H NMR (300 MHz,
DMSO-d6) δH: 10.56 (s, 1H, NH), 8.54 (s, 1H), 8.02 (d, 2H, J=7.3 Hz), 7.90–7.82 (m, 3H), 7.66–7.62 (m,

HETEROCYCLES, Vol. 85, No. 8, 2012
1947
1H), 7.51–7.35 (m, 1H). 13C NMR (75 MHz, CDCl3) δC: 164.7, 151.2, 137.7, 134.5, 134.1, 129.9, 129.3,
128.7, 128.0, 127.6, 127.1, 126.7, 126.2, 124.5, 119.4, 113.4, 101.9. ESI-MS: m/z 303.86 [M+H]+. Anal.
Calcd for C19H14N2S: C, 75.47; H, 4.67; N, 9.26; Found: C, 75.41; H, 4.52; N, 9.30.
4-(4-Fluorophenyl)-N-(naphthalen-2-yl)thiazol-2-amine (3u): Mp 149–150 oC IR (KBr) (νmax, cm-1):
3441, 3059, 2939, 1575, 1494, 1437, 1312, 1223, 1154, 1062. 1H NMR (300 MHz, CDCl3) δH: 7.95–7.78
1
(m, 6H), 7.49–7.35 (m, 3H), 7.14–7.07 (m, 2H), 6.80 (s, 1H), NH not observed. H NMR (300 MHz,
DMSO-d6) δH: 10.54 (s, 1H, NH), 8.51 (s, 1H), 8.06–8.01 (m, 2H), 7.89–7.82 (m, 3H), 7.72–7.27 (m, 6H).
13C NMR (75 MHz, CDCl3) δC: 164.5, 162.6 (d, 1JC-F=245.8 Hz), 150.1, 137.5, 134.1, 130.6 (d, 4JC-F=3.2
3
2
Hz), 130.0, 129.4, 127.8 (d, JC-F=8.1 Hz), 127.7, 127.1, 126.8, 124.7, 119.4, 115.6 (d, JC-F=21.5 Hz),
113.5, 101.5. ESI-MS: m/z 320.99 [M+H]+. Anal. Calcd for C19H13FN2S: C, 71.23; H, 4.09; N, 8.74;
Found: C, 71.19; H, 4.14; N, 8.80.
ACKNOWLEDGEMENTS
We gratefully acknowledge support from the National Natural Science Foundation of China (grant no.
20902035 and 21102042) and Hubei Normal University (2009F014).
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