Porous Ceo2 Nanorod-Catalyzed Synthesis of Poly-Substituted Imino-Pyrrolidine-Thiones

Supporting Information

Porous CeO2 nanorod-catalyzed synthesis of poly-substituted imino-pyrrolidine-thiones

Yuanjiang Wang,a Wenhui Ge,a Yue Fang,a Xuanxuan Ren,c Shinian Cao,c Guixiang Liu,a Mingqi Li,a Jiangbiao Xu,a Yu Wan,b Xiguang Han*a and Hui Wu*ab

a School of Chemistry and Chemical Engineering, Jiangsu Normal University, Xuzhou 221116, P. R. China

b State Key Laboratory Cultivation Construction Base of Biotechnology on Med-edible Plant of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, P. R. China

c Kewen college, Jiangsu Normal University, Xuzhou, 221116, P. R. China.

Synthesis of Porous CeO2 Nanorod:

In a typical synthesis, Ce(NO3)3•6H2O (0.43 g, 1 mmol), (NH4)2CO3 (0.67 g, 7 mmol) were in order added to the mixed solvent of ethanol and distilled water (6 mL, v / v of 1/1) under intense ultrasonic treatment. The resulting solution was transferred into a Teflon-lined stainless-steel autoclave and was kept at 200 ℃for 24 h. The products were collected by centrifugation at 10000 rpm, and washed several times with deionized water and ethanol. The product was calcined at 400 ℃for 10 h.

Synthesis of granular CeO2 nanoparticles:

In a typical synthesis, Ce(NO3)3•6H2O (0.43 g, 1 mmol), CTAB (0.718 g, 2 mmol), H2NCONH2(22 mmol) were in order added to the solvent of deionized water (10 mL) under intense ultrasonic treatment. The resulting solution was transferred into a Teflon-lined stainless-steel autoclave and was kept at 180℃for 24 h. The products were collected by centrifugation at 10000 rpm, and washed 2-3 times with deionized water. The product was calcined at 400 ℃for 10 h.

Figure 1 The typical SEM image of granular CeO2 nanoparticles

Synthesis of fusiform CeO2 nanoparticles:

In a typical synthesis, Ce(NO3)3•6H2O (0.43 g, 1 mmol), CTAB (0.515 g, 1.5 mmol), H2NCONH2(7 mmol) were in order added to the solvent of deionized water (10 mL) under intense ultrasonic treatment. The resulting solution was transferred into a Teflon-lined stainless-steel autoclave and was kept at 120℃for 48 h. The products were collected by centrifugation at 10000 rpm, and washed 2-3 times with deionized water. The product was calcined at 400 ℃for 10 h.

Figure 2 The typical SEM image of fusiform CeO2 nanoparticles

Synthesis of linear CeO2 nanoparticles:

In a typical synthesis, CeCl3•7H2O (0.43 g, 1 mmol), CTAB (1.515 g, 4 mmol), NH3•3H2O (2ml), were in order added to the mixed solvent of ethanol and distilled water (6 mL, v / v of 1/1) under intense ultrasonic treatment. The resulting solution was transferred into a Teflon-lined stainless-steel autoclave and was kept at 200℃for 12 h. The products were collected by centrifugation at 10000 rpm, and washed 2-3 times with deionized water. The product was calcined at 400 ℃for 10 h.

Figure 3 The typical SEM image of linear CeO2 nanoparticles

Typical procedure for synthesis of poly-substituted imino-pyrrolidine-thiones.

In a dry 50 mL round-bottom flask, mixture of aldehyde1 (0.2 mmol), malononitrile2 (0.24 mmol), isocyanide3 (0.24 mmol), benzo[d]oxazole-2-thiol or benzo[d]thiazole-2-thiol4 (0.2 mmol), nanoparticleCeO2 (5 mol %, 0.002g), then CH3CN (3 mL),H2O（1 mL）was added to this mixture.The reaction mixture was stirred at 10 ℃for appropriated time, TLC indicated that the reaction was complete andthenthe reaction mixture was filtered andthe residue was dissolved in CH2Cl2,centrifuged for nanoparticleCeO2 solid, CeO2 solid was washed with ethanol 3 times, after drying under the infrared lamp, CeO2 solid can be used in catalytic reaction 2-3 times repeatly. The filtrate was concentrated on a rotary evaporator under reduced pressure and recrystallized, pure products5 were obtained.

General remarks

IR spectra were recorded with a Varian FTIR-Tensor-27 spectrophotometer using KBr optics. 1H NMR spectra were recorded at 400 MHz on a Bruker DPX 400 spectrometer using TMS as an internal standard and DMSO-d6 or CDCl3-d6 as solvent. Mass was determined by using a Bruker TOF-MS high resolution mass spectrometer. All reagents were obtained from commercial suppliers and used without further purification unless otherwise stated. ([Bmim-G']+HSO4-) was prepared in our lab. Organic solvents were dried and distilled prior to use.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-phenyl-2,3-dihydro-1H-pyrrole-3-carbonitrile (5a)

M.p 183.7-184.1oC. 1H NMR (400 MHz, CDCl3) δ9.16 (s, 1H), 7.81 (d, J = 6.0 Hz, 1H), 7.61 (d, J = 6.7 Hz, 1H), 7.44 (d, J = 10.2 Hz, 5H), 7.16 (d, J = 8.3 Hz, 2H), 5.19 (s, 1H), 5.06 (t, J = 7.6 Hz, 1H), 2.57 (d, J = 9.4 Hz, 2H), 1.97-1.81 (m, 3H), 1.75-1.56 (m, 2H), 1.42 (m, 2H), 1.32 -1.24 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 203.0, 151.4, 135.5, 129.4, 128.3, 126.8, 125.6, 121.1, 111.2, 63.8, 52.5, 30.9, 29.7, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3256, 2922, 2852, 1669, 1557, 1454, 1395, 1365. HRMS (ESI) m/z: calcd for C24H21N4OS [M-H]-: 413.1436; found: 413.1476.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-4-(4-fluorophenyl)-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5b)

M.p 200.0-203.1 oC. 1H NMR (400 MHz, CDCl3)δ 9.16 (s, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.46 (d, J = 7.5 Hz, 2H), 7.28 (s, 1H), 7.25 (s, 1H), 7.12 (d, J = 9.5 Hz, 2H), 5.21 (s, 1H), 5.05 (t, J = 9.1 Hz, 1H), 2.55 (m, 2H), 1.97 – 1.79 (m, 3H), 1.75-1.61 (m, 2H), 1.59-1.20 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ203.0, 164.4, 161.9, 160.5, 156.6, 151.5, 140.1, 131.3, 130.4, 126.9, 125.7, 121.1, 116.6, 116.4, 113.0, 111.3, 62.8, 58.9, 52.3, 27.6, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3243, 2933, 2852, 1677, 1560, 1509, 1372. HRMS (ESI) m/z: calcd for C24H20FN4OS [M-H]-: 431.1342; found: 431.1380.

3-(benzo[d]oxazol-2-yl)-4-(4-chlorophenyl)-1-cyclohexyl-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5c)

M.p 176.5-179.6 oC. 1H NMR (400 MHz, CDCl3) δ9.18 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.43 (m, 4H), 7.22 (d, J = 8.3 Hz, 2H), 5.20 (s, 1H), 5.04 (m, 1H), 2.55 (m, 2H), 1.84 (m, 3H), 1.68 (m, 2H), 1.41 (m, 2H), 1.32-1.22 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)δ 202.7, 151.5, 135.6, 133.8, 129.9 129.6, 126.9, 125.7, 121.1, 113.0, 111.3, 62.9, 52.1, 27.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3252, 2931, 2856, 1675, 1561, 1492, 1453, 1370, 1340. HRMS (ESI) m/z: calcd for C24H20ClN4OS [M-H]-: 447.1046; found: 447.1078.

3-(benzo[d]oxazol-2-yl)-4-(4-bromophenyl)-1-cyclohexyl-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5d)

M.p 194.8-198.3 oC. 1H NMR (400 MHz, CDCl3) δ9.15 (s, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 8.3 Hz, 2H), 7.51-7.41 (m, 2H), 7.16 (d, J = 8.3 Hz, 2H), 5.19 (s, 1H), 5.04 (s, 1H), 2.54 (m, 2H), 1.89 (m, 3H), 1.75-1.61 (m, 2H), 1.41 (m, 2H), 1.31-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ202.6, 151.5, 134.3, 132.6, 130.2, 126.9, 125.7, 123.8, 121.1, 113.0, 111.3, 62.9, 58.9, 52.0, 27.6, 26.7, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3252, 2931, 2852, 1676, 1561, 1489, 1453, 1369, 1340. HRMS (ESI) m/z: calcd for C24H20BrN4OS [M-H]-: 491.0541; found: 491.0567.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-4-(4-iodophenyl)-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5e)

M.p 200.1-203.1 oC. 1H NMR (400 MHz, CDCl3) δ 9.17 (s, 1H), 7.78 (m, 3H), 7.62 (d, J = 7.8 Hz, 1H), 7.52 - 7.41 (m, 2H), 7.02 (d, J = 7.8 Hz, 2H), 5.17 (s, 1H), 5.04 (t, J = 5.6 Hz, 1H), 2.56 (m, 2H), 1.97-1.78 (m, 3H), 1.65 (m, 2H), 1.41 (m, 2H), 1.31-1.22 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 202.5, 160.5, 156.5, 151.5, 140.1, 138.5, 134.9, 130.3, 126.9, 125.7, 121.1, 112.9, 111.3, 95.6, 63.1, 58.9, 52.0, 30.9, 27.6, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3253, 2933, 2851, 1674, 1560, 1370.HRMS (ESI) m/z: calcd for C24H20IN4OS [M-H]-: 539.0402; found: 539.0469.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-(4-nitrophenyl)-2,3-dihydro-1H-pyrrole-3-carbonitrile (5f)

M.p 190.1-191.9 oC. 1H NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.29 (d, J = 8.2 Hz, 2H), 7.83 (d, J = 7.2 Hz, 1H), 7.64 (d, J = 7.3 Hz, 1H), 7.49 (t, J = 9.3 Hz, 4H), 5.41 (s, 1H), 5.04 (t, J = 9.2 Hz, 1H), 2.57 (m, 2H), 1.97-1.81 (m, 3H), 1.67 (m, 2H), 1.49 -1.36 (m, 2H), 1.33-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 203.0, 151.6, 148.3, 142.0, 130.1, 127.1, 125.8, 124.4, 121.2, 111.3, 62.5, 59.1, 51.5, 30.9, 27.5, 26.7, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3240, 2929, 1675, 1560, 1520, 1372.HRMS (ESI) m/z: calcd for C24H20N5O3S [M-H]-: 458.1287; found: 458.1230.

3-(benzo[d]oxazol-2-yl)-4-(4-cyanophenyl)-1-cyclohexyl-2-imino-5-thioxopyrrolidine-3-carbonitrile (5g)

M.p 161.0-162.0 oC. 1H NMR (400 MHz, CDCl3) δ9.23 (s, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 7.9 Hz, 1H), 7.50 – 7.41 (m, 4H), 5.33 (s, 1H), 5.04 (m, 1H), 2.70-2.43 (m, 2H), 1.89 (m, 3H), 1.72-1.63 (m, 2H), 1.45-1.36 (m, 2H), 1.29 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 201.5, 140.1, 133.0, 129.8, 127.1, 125.8, 121.2, 118.0, 113.5, 112.8, 111.3, 62.8, 59.0, 51.6, 27.5, 26.7, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3257, 2932, 2854, 2235, 1673, 1561, 1374. HRMS (ESI) m/z: calcd for C25H20N5OS [M-H]-: 438.1489; found: 438.1438.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-4-(3-fluorophenyl)-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5h)

M.p 173.5-175.4 oC. 1H NMR (400 MHz, CDCl3) δ 9.23 (s, 1H), 7.82 (d, J = 7.7 Hz, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.63 (d, J = 7.9 Hz, 1H), 7.50-7.41 (m, 4H), 5.33 (s, 1H), 5.04 (m, 1H), 2.70-2.43 (m, 2H), 1.89 (m, 3H), 1.66 (m, 2H), 1.42 (m, 2H), 1.32-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 164.1, 151.5, 131.0, 126.9, 125.7, 124.2, 121.2, 116.7, 116.5, 115.9, 115.7, 111.3, 63.1, 58.9, 52.1, 30.9 27.6, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3255, 2932, 1672, 1560, 1368. HRMS (ESI) m/z: calcd for C24H20FN4OS [M-H]-: 431.1342; found: 431.1391.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-4-(3-nitrophenyl)-5-thioxopyrrolidine-3-carbonitrile (5i)

M.p 166.8-167.5 oC. 1H NMR (400 MHz, CDCl3) δ9.28 (s, 1H), 8.30 (d, J = 5.2 Hz, 1H), 8.23 (s, 1H), 7.84 (d, J = 7.4 Hz, 1H), 7.65 (d, J = 6.4 Hz, 3H), 7.54 -7.42 (m, 2H), 5.42 (s, 1H), 5.06 (t, J = 9.1 Hz, 1H), 2.57 (m, 2H), 1.91 (m, 3H), 1.70 (m, 2H), 1.43 (m, 2H), 1.33-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 201.4, 159.8, 156.1, 151.6, 148.5, 140.0, 137.1, 134.9, 130.3, 127.1, 125.8, 124.3, 121.2, 112.8, 111.3, 62.4, 59.1, 51.5, 30.9, 27.5, 26.8, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3279, 2921, 2856, 1672, 1537, 1372. HRMS (ESI) m/z: calcd for C24H20N5O3S [M-H]-: 458.1287; found: 458.1324.

3-(benzo[d]oxazol-2-yl)-4-(2-bromophenyl)-1-cyclohexyl-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5j)

M.p 181.9-183.3 oC. 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 7.83 (d, J = 7.3 Hz, 1H), 7.64 (m, 2H), 7.50-7.35 (m, 3H), 7.29 (d, J = 7.7 Hz, 1H), 7.12 (d, J = 7.7 Hz, 1H), 5.76 (s, 1H), 5.11 (t, J = 9.3 Hz, 1H), 2.55 (d, J = 9.6 Hz, 2H), 1.98-1.81 (m, 3H), 1.69 (t, J = 9.3 Hz, 2H), 1.44 (m, 2H), 1.33-1.22 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ202.6, 160.7, 157.0, 151.4, 140.3, 135.7, 133.4, 130.8, 128.5, 126.7, 126.0, 125.5, 121.2, 112.7, 111.2, 63.0, 58.9, 52.1, 30.9, 27.8, 26.5, 25.9, 25.7, 25.0 ppm. IR (KBr) max cm-1: 3217, 2935, 2853, 1683, 1569, 1349. HRMS (ESI) m/z: calcd for C24H20BrN4OS [M-H]-: 447.1046; found: 447.1104.

3-(benzo[d]oxazol-2-yl)-4-(4-bromo-2-fluorophenyl)-1-cyclohexyl-2-imino-5-thioxopyrrolidine-3-carbonitrile (5k)

M.p 168.2-171.1 oC. 1H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 7.80 (d, J = 7.7 Hz, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.51-7.41 (m, 2H), 7.35 (t, J = 9.8 Hz, 2H), 7.18 (t, J = 7.9 Hz, 1H), 5.37 (s, 1H), 5.03 (m, 1H), 2.53 (s, 2H), 1.86 (m, 3H), 1.75-1.59 (m, 2H), 1.45-1.20 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 201.5, 161.9, 160.5, 159.4, 156.7, 151.6, 140.1, 128.4, 126.9, 125.7, 124.3, 122.3, 121.1, 120.2, 120.0, 112.9, 111.3, 59.1, 50.6, 27.2, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3255, 2934, 1676, 1561, 1372. HRMS (ESI) m/z: calcd for C24H19BrFN4OS [M-H]-: 509.0447; found: 509.0491.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-(4-methoxyphenyl)-2,3-dihydro-1H-pyrrole-3-carbonitrile (5l)

M.p 92.2-94.2 oC. 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J = 6.8 Hz, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.50-7.40 (m, 2H), 7.18 (d, J = 8.2 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 5.13 (s, 1H), 5.06 (t, J = 9.6 Hz, 1H), 3.81 (s, 3H), 2.66-2.44 (m, 2H), 1.88 (m, 3H), 1.68 (m, 2H), 1.46-1.33 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 203.0, 160.2, 129.6, 126.8, 125.6, 121.1, 114.8, 111.2, 63.2, 58.7, 55.2, 30.9, 27.6, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3279, 2935, 2853, 1672, 1592, 1558, 1455, 1339. HRMS (ESI) m/z: calcd for C25H23N4O2S [M-H]-: 443.1542; found: 443.1578.

3-(benzo[d]oxazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-(3,4,5-trimethoxyphenyl)-2,3-dihydro-1H-pyrrole-3-carbonitrile (5m)

M.p 169.4-170.3 oC. 1H NMR (400 MHz, CDCl3)δ9.20 (s, 1H), 7.81 (d, J = 7.4 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.51-7.41 (m, 2H), 6.45 (s, 2H), 5.12-5.01 (m, 2H), 3.85 (d, J = 6.8 Hz, 9H), 2.59 (m, 2H), 1.87 (m, 3H), 1.73-1.59 (m, 2H), 1.46-1.23 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 203.0, 156.7, 153.7, 151.4, 140.2, 138.8, 130.6, 126.9, 125.6, 121.1, 113.0, 111.2, 105.3, 64.0, 60.9, 58.6, 56.1, 52.8, 30.9, 27.6, 26.5, 25.9, 25.7, 25.0 ppm. IR (KBr) max cm-1: 3261, 2938, 1672, 1592, 1558, 1455, 1339. HRMS (ESI) m/z: calcd for C27H27N4O4S [M-H]-: 503.1753; found: 503.1780.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-phenyl-2,3-dihydro-1H-pyrrole-3-carbonitrile (5n)

M.p 165.2-166.4 oC. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.1 Hz, 1H), 7.92 (m, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.41 (d, J = 5.2 Hz, 3H), 7.24 (d, J = 3.8 Hz, 2H), 5.12 (s, 1H), 5.06 (d, J = 12.4 Hz, 1H), 2.59 (m, 2H), 1.90 (d, J = 15.1 Hz, 3H), 1.71 (d, J = 9.0 Hz, 2H), 1.47-1.35 (m, 2H), 1.30 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 203.8, 152.7, 135.9, 129.4, 128.2, 127.2, 126.7, 124.2, 121.8, 114.7, 66.2, 27.8, 26.5, 25.8, 25.1ppm. IR (KBr) max cm-1: 3267, 2936, 2854, 1666, 1491, 1458, 1392. HRMS (ESI) m/z: calcd for C24H21N4S2 [M-H]-: 429.1208; found: 429.1175.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-4-(4-fluorophenyl)-2-imino-5-thioxopyrrolidine-3-carbonitrile (5o)

M.p 163.2-165.8 oC. 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.58 (m, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 5.1 Hz, 2H), 7.10 (t, J = 8.5 Hz, 2H), 5.15 (s, 1H), 5.12-5.01 (m, 1H), 2.54 (m, 2H), 1.97-1.82 (m, 3H), 1.70 (m, 2H), 1.46-1.36 (m, 2H), 1.28 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 153.7, 130.2, 127.2, 126.7, 124.2, 121.9, 116.6, 116.4, 66.4, 60.9, 58.4, 56.9, 56.1, 25.8, 25.1 ppm.IR (KBr) max cm-1: 3266, 2931, 2854, 1716, 1667, 1368.HRMS (ESI) m/z: calcd for C24H20FN4S2 [M-H]-: 447.1113; found: 447.1178.

3-(benzo[d]thiazol-2-yl)-4-(4-chlorophenyl)-1-cyclohexyl-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5p)

M.p 137.5-138.8 oC. 1H NMR (400 MHz, CDCl3) δ8.10 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.19 (d, J = 8.3 Hz, 2H), 5.15 (s, 1H), 5.05 (t, J = 12.1 Hz, 1H), 2.53 (m, 2H), 1.86 (m, 3H), 1.69 (m, 2H), 1.45-1.36 (m, 2H), 1.28 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 135.5, 134.2, 129.7, 127.3, 126.8, 124.2, 121.9, 65.4, 58.7, 56.3, 27.7, 26.5, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3290, 2925, 2856, 1670, 1490, 1456, 1392, 1377, 1306.HRMS (ESI) m/z: calcd for C24H20ClN4S2 [M-H]-: 463.0818; found: 463.0783.

3-(benzo[d]thiazol-2-yl)-4-(4-bromophenyl)-1-cyclohexyl-2-imino-5-mercapto-2,3-dihydro-1H-pyrrole-3-carbonitrile (5q)

M.p 143.0-144.1 oC. 1H NMR (400 MHz, CDCl3) δ8.99 (s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.61 (m, 4H), 7.13 (d, J = 8.3 Hz, 2H), 5.13 (s, 1H), 5.10 (m, 1H), 2.50 (d, J = 50.2 Hz, 2H), 1.90 (m, 3H), 1.69 (s, 2H), 1.46-1.35 (m, 2H), 1.29 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 134.7, 132.6, 130.0, 127.0, 126.8, 124.2, 123.7, 121.9, 65.4, 58.7, 27.7, 26.5, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3293, 2927, 2856, 1672, 1488, 1450, 1394, 1376, 1305. HRMS (ESI) m/z: calcd for C24H20BrN4S2 [M-H]-: 507.1313; found: 507.1313.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-2-imino-4-(4-iodophenyl)-5-thioxopyrrolidine-3-carbonitrile (5r)

M.p 120.4-123.8 oC. 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.73 (s, 2H), 7.58 (t, J = 7.7 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 8.2 Hz, 2H), 5.12-5.00 (m, 2H), 2.56 (m, 2H), 1.95-1.81 (m, 3H), 1.69 (s, 2H), 1.42 (m, 2H), 1.32-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 161.8, 138.5, 135.0, 130.1, 127.3 126.8, 124.2, 121.9, 114.6, 95.5, 65.6, 58.7, 56.1, 27.6, 26.5, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3261, 2933, 2854, 1671, 1377. HRMS (ESI) m/z: calcd for C24H20IN4S2 [M-H]-: 555.0174; found: 555.0166.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-2-imino-5-mercapto-4-(4-nitrophenyl)-2,3-dihydro-1H-pyrrole-3-carbonitrile (5s)

M.p 173.0-175.0 oC. 1H NMR (400 MHz, CDCl3)δ 8.28 (d, J = 8.6 Hz, 2H), 8.12 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.53 (t, J = 7.6, 7.6 Hz, 1H), 7.46 (d, J = 8.6 Hz, 2H), 5.36 (s, 1H), 5.06 (t, J = 7.0, 7.0 Hz, 1H), 2.54 (m, 2H), 1.96 – 1.84 (m, 3H), 1.70 (s, 2H), 1.46 -1.37 (m, 2H), 1.30 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 142.4, 129.8, 127.4, 126.9, 124.5, 124.3, 121.9, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3245, 2931, 2854, 1674, 1521, 1490, 1456, 1373, 1349. HRMS (ESI) m/z: calcd for C24H20N5O2S2 [M-H]-: 474.1058; found: 474.1058.

3-(benzo[d]thiazol-2-yl)-4-(4-cyanophenyl)-1-cyclohexyl-2-imino-5-thioxopyrrolidine-3-carbonitrile (5t)

M.p 179.6-181.7 oC. 1H NMR (400 MHz, CDCl3) δ 9.00 (s, 1H), 8.11 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.1 Hz, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.60 (t, J = 7.7 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.38 (s, 2H), 5.28 (s, 1H), 5.05 (t, J = 9.3 Hz, 1H), 2.53 (m, 2H), 1.98-1.82 (m, 3H), 1.72 (d, J = 8.6 Hz, 2H), 1.47-1.35 (m, 2H), 1.33-1.24 (m, 1H)ppm. 13C NMR (100 MHz, CDCl3) δ 152.6, 140.6, 133.0, 129.5, 127.4, 126.9, 124.2, 121.9, 118.0, 113.3, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3292, 2931, 2855, 2231, 1681, 1396, 1381. HRMS (ESI) m/z: calcd for C25H20N5S2 [M-H]-: 454.1160; found:454.1152.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-4-(3-fluorophenyl)-2-imino-5-thioxopyrrolidine-3-carbonitrile (5u)

M.p 166.8-168.0 oC. 1H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.40 (m, 1H), 7.11 (t, J = 8.4 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 6.96 (d, J = 9.2 Hz, 1H), 5.16 (s, 1H), 5.11-5.01 (m, 1H), 2.66-2.42 (m, 2H), 1.96-1.83 (m, 3H), 1.70 (s, 2H), 1.47-1.35 (m, 2H), 1.30 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 202.8, 162.7, 161.9, 161.7, 152.6, 135.0, 131.1), 127.3, 126.8, 124.2, 121.9, 116.6, 116.4, 115.7, 115.5, 114.5, 65.6, 58.7), 56.3, 27.7, 26.4, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3226, 2934, 2849, 1683, 1589, 1396. HRMS (ESI) m/z: calcd for C24H20FN4S2 [M-H]-: 447.1113; found: 447.1184.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-2-imino-4-(3-nitrophenyl)-5-thioxopyrrolidine-3-carbonitrile (5v)

M.p 134.1-136.0 oC. 1H NMR (400 MHz, CDCl3) δ8.29 (s, 1H), 8.17 (s, 1H), 8.13 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.61 (m, 3H), 7.53 (t, J = 7.6 Hz, 1H), 5.37 (s, 1H), 5.12-5.02 (m, 1H), 2.69-2.45 (m, 2H), 1.97-1.85 (m, 3H), 1.72 (m, 2H), 1.44 (m, 2H), 1.33-1.25 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3)δ201.8, 162.0, 161.2, 148.5, 137.5, 135.0, 134.6, 130.4, 127.5, 127.0, 124.3, 124.0, 121.9, 114.5, 64.9, 58.9, 55.8, 27.6, 26.6, 25.8, 25.0 ppm. IR (KBr) max cm-1: 3261, 2931, 2854, 1669, 1353. HRMS (ESI) m/z: calcd for C24H20N5O2S2 [M-H]-: 474.1058; found: 474.1047.

3-(benzo[d]thiazol-2-yl)-4-(2-bromophenyl)-1-cyclohexyl-2-imino-5-thioxopyrrolidine-3-carbonitrile (5w)

M.p 145.6-147.9 oC. 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.29 (s, 1H), 7.08 (d, J = 7.7 Hz, 1H), 5.66 (s, 1H), 5.17- 5.06 (m, 1H), 2.55 (m, 2H), 1.91 (s, 3H), 1.71 (m, 2H), 1.48-1.38 (m, 2H), 1.32-1.23 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 152.7, 136.2, 133.4, 130.7, 128.5, 128.1, 127.1, 126.6, 126.2, 124.3, 121.8, 26.0, 25.7, 25.1. IR (KBr) max cm-1: 3287, 2932, 2866, 1679, 1393.HRMS (ESI) m/z: calcd for C24H20BrN4S2 [M-H]-: 507.0313; found: 507.0378.

3-(benzo[d]thiazol-2-yl)-4-(4-bromo-2-fluorophenyl)-1-cyclohexyl-2-imino-5-thioxopyrrolidine-3-carbonitrile (5x)

M.p 163.6-164.8 oC. 1H NMR (400 MHz, CDCl3) δ8.99 (s, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.61-7.54 (m, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.35 (t, J = 8.0 Hz, 2H), 7.14 (t, J = 8.0 Hz, 1H), 5.31 (s, 1H), 5.04 (m, 1H), 2.60-2.42 (m, 2H), 1.97-1.81 (m, 3H), 1.69 (s, 2H), 1.46 -1.33 (m, 2H), 1.32 -1.22 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 201.9, 152.6, 128.4, 127.3, 126.8, 124.2, 121.9, 120.2, 119.9, 58.9, 27.4, 26.4, 25.8, 25.1. IR (KBr) max cm-1: 3288, 2935, 2855, 1680, 1307. HRMS (ESI) m/z: calcd for C24H19BrFN4S2 [M-H]-: 525.0219; found: 525.0305.

3-(benzo[d]thiazol-2-yl)-1-cyclohexyl-2-imino-5-thioxo-4-(3,4,5-trimethoxyphenyl)pyrrolidine-3-carbonitrile (5y)

M.p 159.1-163.1oC. 1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.9 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H), 7.53-7.48 (m, 1H), 6.44 (s, 2H), 5.04 (s, 1H), 3.83 (s, 9H), 3.42 (s, 1H), 2.54 (m, 2H), 1.94-1.84 (m, 3H), 1.70 (t, J = 13.6 Hz, 3H), 1.43 (m, 2H), 1.32 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3) δ 153.7, 131.1, 127.2, 126.7, 124.2, 121.8, 105.0, 66.4, 60.9, 58.4, 56.9, 56.1, 27.6, 26.3, 25.9, 25.7, 25.0 ppm. IR (KBr) max cm-1: 3268, 2932, 2854, 1716, 1561, 1372. HRMS (ESI) m/z: calcd for C27H27N4O3S2 [M-H]-: 519.1525; found: 519.1548.

Figure 1 1H NMR spectrum of compound 5c (CDCl3, 400 MHz)

Figure 2 13C NMR spectrum of compound 5c(CDCl3, 100 MHz)

Figure 3 FT-IR spectrum of 5c

Figure 4 High resolution mass spectrum of 5c

Figure 5 1H NMR spectrum of compound 5e (CDCl3, 400 MHz)

Figure 613C NMR spectrum of compound 5e (CDCl3, 100 MHz)

Figure 7 FT-IR spectrum of 5e

Figure 8 High resolution mass spectrum of 5e

Figure9 1H NMR spectrum of compound 5r(CDCl3, 400 MHz)

Figure 1013C NMR spectrum of compound 5r(CDCl3, 100 MHz)

Figure 11 FT-IR spectrum of 5r

Figure 12 High resolution mass spectrum of 5r