HETEROCYCLES

Paper | Regular issue | Vol. 85, No. 8, 2012, pp. 1941-1948
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, Hubei, China

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

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 30% yields respectively (entries 9, 10). Its structure was assigned on the basis of 1H NMR and mass spectra. The 1H 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-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).

EXPERIMENTAL
All reagents were purchased from commercial suppliers and used without further purification. All solvents were of analytical grade and dried according to published methods and distilled before use. 1H and 13C 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 by TLC or crude 1H 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.
4-Phenylthiazol-2-amine (3a): Mp 149–150 oC (lit.,12 150–151 oC). IR (KBr) (νmax, cm-1): 3433, 3256, 1598, 1522, 1336, 1034, 712. 1H 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]+.
4-(4-Methoxyphenyl)thiazol-2-amine (3b): Mp 206–207 oC (lit.,12 206–207 oC). 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, 1493, 1239, 1034. 1H 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.
4-(4-Fluorophenyl)thiazol-2-amine (3d): Mp 103–104 oC (lit.,12 102–103 oC). IR (KBr) (νmax, cm-1): 3450, 3285, 3114, 1630, 1528, 1484, 1336. 1H 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, 1JC-F=245.3 Hz), 150.2, 130.9 (d, 4JC-F=3.3 Hz), 127.7 (d, 3JC-F=8.0 Hz), 115.6 (d, 2JC-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, 1317, 1034, 751, 709. 1H 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]+.
4-(Naphthalen-2-yl)thiazol-2-amine (3f): Mp 150–151 oC (lit.,13 153–154 oC). IR (KBr) (νmax, cm-1): 3432, 3258, 1602, 1524, 1317. 1H 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]+.
N-Methyl-4-phenylthiazol-2-amine (3g): Mp 125–126 oC (lit.,13 136–137 oC). 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, 1449. 1H 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.
N-Methyl-4-(thiophen-2-yl)thiazol-2-amine (3i)20: Mp 108–109 oC. 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 (d, 3H, J=4.8 Hz). 13C 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]+.
N-Allyl-4-phenylthiazol-2-amine (3j): Mp 72–73 oC (lit.,13 73 oC). IR (KBr) (νmax, cm-1): 3449, 3194, 2966, 1581, 1416, 1321, 915, 702. 1H 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, 2H). 13C 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, 1573, 1414, 1328, 1236, 1021. 1H 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 (s, 2H), 3.83 (s, 3H). 13C 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, 2878, 1574, 1489, 1325, 1225. 1H 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). 13C NMR (75 MHz, CDCl3) δC: 170.1, 162.3 (d, 1JC-F=245.1 Hz), 150.2, 133.3 (d, 4JC-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, 3087, 2966, 1580, 1418, 1354, 1290, 1233. 1H NMR (300 MHz, CDCl3) δH: 8.33 (s, 1H), 7.90–7.80 (m, 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.
N-Allyl-4-(furan-2-yl)thiazol-2-amine (3o): Mp 81–83 oC (lit.,17 104 oC). IR (KBr) (νmax, cm-1): 3443, 3210, 3004, 1548, 1451, 1195, 1073, 1003, 935. 1H 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, 1542, 1580, 1415, 1356, 1294, 1220. 1H 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.
N,4-Diphenylthiazol-2-amine (3q): Mp 137–138 oC (lit.,19 135–136 oC). IR (KBr) (νmax, cm-1): 3448, 3228, 2951, 1605, 1583, 1467, 1423, 1310. 1H 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]+.
4-(4-Methoxyphenyl)-N-phenylthiazol-2-amine (3r): Mp 139–141 oC (lit.,19 138–139 oC). 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, cm-1): 3436, 1604, 1560, 1489, 1412, 1307, 1225, 837, 741, 688. 1H 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 (m, 3H), 7.78–7.73 (m, 3H), 7.47–7.25 (m, 6H), 6.87 (s, 1H), NH not observed. 1H 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, 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 (m, 6H), 7.49–7.35 (m, 3H), 7.14–7.07 (m, 2H), 6.80 (s, 1H), NH not observed. 1H 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 Hz), 130.0, 129.4, 127.8 (d, 3JC-F=8.1 Hz), 127.7, 127.1, 126.8, 124.7, 119.4, 115.6 (d, 2JC-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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