4.3. Purification Conditions and Spectroscopic Data
(4
RS)-4-Benzyl-5-phenyl-3,4-dihydropyridine-2(1
H)-thione [
9] (
S1): The crude product purified by column chromatography on silica gel using a mixture of ethyl acetate and
n-hexane yielded pale yellow solid in 68%. Mp. 143–144 °C (
n-hexane: ethyl acetate).
1H NMR (400 MHz, CDCl
3) δ 2.58 (dd,
J = 13.6, 10.9 Hz, 1 H, 4-C
HH), 2.79 (dd,
J = 17.3, 7.1 Hz, 1 H, C
HH-3), 2.83 (dd,
J = 13.6, 3.7 Hz, 1 H, 4-CH
H), 2.98–3.05 (m, 1 H, CH-4), 3.21 (d,
J = 17.3 Hz, 1 H, CH
H-3), 6.56 (d,
J = 4.6 Hz, 1 H, =CH-6), 7.21–7.48 (m, 10 H, 2× C
6H
5), 9.66 (br. s., 1 H, NH).
13C NMR (100.6 MHz CDCl
3): δ 35.73 (CH-4), 37.11 (4-CH
2), 41.68 (CH
2-3), 120.13 (=CH-6), 124.95, 126.53 (C
6H
5), 126.99 (C-5), 127.71, 128.50, 128.98, 129.55, 136.12, 138.48 (C
6H
5), 197.96 (C=S). GC-MS (EI, 70 eV):
m/z = 279 (36), [M
+], 188 (100), 154 (19), 128 (30), 91 (15). HRMS (ESI-TOF): calcd. for C
18H
18NS 280.1160 [M + H]
+; found 280.1166.
(4RS)-4-Benzyl-1-methyl-5-phenyl-3,4-dihydropyridine-2(1H)-thione (S2): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 9: 1, the second column: SiO2, chloroform), gave yellow solid in 96% yield. Mp. 127–129 °C (petroleum ether: ethyl acetate). 1H NMR (400 MHz, CDCl3) δ 2.53 (dd, J = 13.5, 10.3 Hz, 1H, 4-CHH), 2.79 (dd, J = 13.5, 3.6 Hz, 1H, 4-CHH), 2.88 (ddq, J = 16.3, 6.5 Hz, 0.9 1H, CHH-3), 2.95 (dddd, 10.3, 6.5, 3.6, 1.5, 1H, CH-4), 3.34 (dd, J = 16.3, 1.5 Hz, 1H, CHH-3), 3.59 (d, J = 0.9 Hz, 3H, NCH3), 6.64 (s, 1H, =CH-6), 7.16–7.26 (m, 3H, C6H5), 7.26–7.34 (m, 3H, C6H5), 7.35–7.43 (m, 2H, C6H5), 7.43–7.48 (m, 2H, C6H5). 13C NMR (101 MHz CDCl3) δ 35.86 (CH-4), 37.29 (4-CH2), 42.27 (N-CH3), 44.19 (CH2-3), 125.07 (C6H5), 126.40 (=CH-6), 126.49, 127.75 (C6H5), 128.18 (=C-5), 128.39 128.99, 129.61, 136.18, 138.59 (C6H5), 195.72 (C=S). GC-MS (EI, 70 eV): m/z = 293 (19), [M+], 204 (6), 203 (15), 202 (100), 201 (7), 186 (4), 170 (4), 168 (5), 128 (14), 127 (5), 115 (7), 91(9). HRMS (ESI-TOF): m/z [M++H] calcd. for C19H20NS 294.1316; found: 294.1323.
(4RS)-4-Benzyl-5-phenyl-1-propyl-3,4-dihydropyridine-2(1H)-thione (S3): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 10: 1, the second column: SiO2, chloroform), gave yellow solid in 89% yield. Mp. 105–107 °C (petroleum ether: ethyl acetate). 1H NMR (400 MHz, CDCl3) δ 1.02 (t, J = 7.4 Hz, 3H, N-CH3), 1.72–1.89 (m, 2H, CH2) 2.53 (dd, J = 13.5, 10.3 Hz, 1H, 4-CHH), 2.78 (dd, J = 13.5, 3.6 Hz, 1H, 4-CHH), 2.86 (dd, J = 16.2, 6.6 Hz, 1H, CHH-3), 2.89–3.00 (m, 1H, CH-4), 3.34 (dd, J = 16.2, 1.5, 1H, CHH-3), 3.83 (ddd, J = 13.1, 8.7, 6.5 Hz, 1H, NCHH), 4.38 (ddd, J = 13.0, 8.8, 6.4 Hz, 1H, NCHH), 6.63 (s, 1H, =CH-6), 7.14–7.34 (m, 6H, C6H5), 7.37–7.48 (m, 4H, C6H5). 13C NMR (101 MHz CDCl3): δ 11.36 (CH3), 20.57 (CH2), 35.76 (CH-4), 37.03 (4-CH2), 44.55 (CH2-3), 55.24 (NCH2), 125.06 (C6H5), 125.47(=CH-6), 126.46, 127.69 (C6H5), 128.36 (=C-5), 128.41, 128.95, 129.60, 136.31, 138.64 (C6H5), 195.29 (C=S). GC-MS (EI, 70 eV): m/z = 321 (27), [M+], 230 (100), 188 (44), 154 (15), 128 (19), 91 (16), 65 (5). HRMS (ESI-TOF): m/z calcd for C21H24NS [M+H]+, 322.1629; found: 322.1635.
(4RS)-1,4-Dibenzyl-5-phenyl-3,4-dihydropyridine-2(1H)-thione (S4): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 9: 1, the second column: SiO2, chloroform), gave yellow solid in 85% yield. Mp. 73–76 °C (petroleum ether: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.54 (dd, J = 13.6, 9.8 Hz, 1H, 4-CHH), 2.77 (dd, J = 13.6, 3.5 Hz, 1H, 4-CHH), 2.92–2.99 (m, 2H, CHH-3, CH-4), 3.41–3.48 (m, 1H, CHH-3), 5.39 (d, J = 14.8 Hz, 1H, NCHH), 5.53 (d, J = 14.8 Hz, 1H, NCHH), 6.64 (s, 1H, =CH-6), 7.20–7.45 (m, 15H, C6H5). 13C NMR (101 MHz CDCl3): δ 35.91 (CH-4), 37.02 (4-CH2), 44.56 (CH2-3), 55.88 (NCH2), 124.77 (=CH-6), 125.10, 126.49, 127.72, 127.78, 127.96, 128.43 (C6H5), 128.71 (=C-5), 128.85, 128.88, 129.58, 135.70, 136.16, 138.61 (C6H5), 196.49 (C=S). GC-MS (EI, 70 eV): m/z = 369 (11), [M+], 279 (8), 278 (40), 123 (5), 92 (8), 91 (100), 65 (7). HRMS (ESI-TOF): m/z calcd for C25H24NS [M+H]+, 370.1629; found: 370.1633.
(6RS)-6-Benzyl-5-phenyl-3,6-dihydropyridine-2(1H)-thione (S6): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 6: 1, the second column: SiO2, chloroform), gave pale yellow solid in 90% yield. Mp. 137–138 °C (petroleum ether: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.72 (dd, J = 13.8, 6.4 Hz 1H, 6-CHH), 2.79 (dt, J = 23.2, 3.1 Hz, 1H, CHH-3), 3.07 (dd, J = 13.8, 3.8 Hz, 1H, 6-CHH), 3.48 (ddd, J = 23.2, 5.1, 3.1 Hz, 1H, CHH-3), 4.86 (ddt, J = 6.4, 3.1, 3.8 Hz, 1H, CH-6), 5.90 (dd, J = 5.1, 3.1 Hz, 1H, =CH-4), 7.00–7.14 (m, 2H, C6H5), 7.24–7.34 (m, 3H, C6H5), 7.34–7.53 (m, 5H, C6H5), 9.26 (br. s, 1H, NH). 13C NMR (101 MHz CDCl3): δ 40.00 (CH2-3), 40.83 (6-CH2), 58.3 (CH-6), 120.60 (=CH-4), 126.00, 127.23, 128.55, 129.03, 130.05 (C6H5), 134.27 (=C-5), 135.22, 137.27 (C6H5), 199.5 (C=S). GC-MS (EI, 70 eV): m/z = 279 (27), [M+], 188 (100), 154 (19), 128 (29), 91 (16). HRMS (ESI-TOF): m/z calcd for C18H18NS [M+H]+, 280.1160; found: 280.1161.
(6RS)-6-Benzyl-1-methyl-5-phenyl-3,6-dihydropyridine-2(1H)-thione (S7): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 6: 1, the second column: SiO2, chloroform), gave dark red oil in 78% yield. 1H NMR (400 MHz, CDCl3): δ 2.22 (ddd, J = 22.6, 3.5, 2.2 Hz, 1H, CHH-3), 2.78 (dd, J = 13.9, 4.1 Hz, 1H, 6-CHH), 3.18 (dd, J = 13.9, 4.5 Hz, 1H, 6-CHH), 3.51 (ddd, J = 22.4, 5.7, 1.9 Hz, 1H, CHH-3), 3.62 (d, J = 0.8 Hz, 3H, N-CH3), 4.92 (dddd, J = 4.5, 4.1, 3.4, 1.9 Hz, 1H, CH-6), 5.9 (dd, J = 5.7, 2.2 Hz, 1H, =CH-4), 6.78–7.06 (m, 2H, C6H5), 7.12–7.31 (m, 3H, C6H5), 7.32–7.48 (m, 5H, C6H5). 13C NMR (101 MHz CDCl3): δ 37.64 (6-CH2), 42.46 (CH2-3), 42.73 (NCH3), 66.24 (CH-6), 121.50 (=CH-4), 125.85, 127.39, 128.22, 128.29, 129.04, 130.13 (C6H5), 134.66 (=C-5), 134.73, 137.06 (C6H5), 197.40 (C=S). GC-MS (EI, 70 eV): m/z = 293 (22), [M+], 202 (100), 170 (6), 128 (11), 91 (8), 65 (63), 42 (8). HRMS (ESI-TOF): m/z calcd for C19H20NS [M+H]+, 294,1316; found: 294,1314.
(4RS)-4-Benzyl-5-(4-fluorophenyl)-3,4-dihydropyridine-2(1H)-thione (S8): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 10: 1, the second column: SiO2, chloroform), gave yellow solid in 90% yield. Mp. 144–147 °C (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.57 (dd, J = 13.7, 10.7 Hz, 1H, 4-CHH), 2.73–2.84 (m, 2H, 4-CHH, CHH-3), 2.96 (dddd, J = 10.7, 6.2, 4.0, 1.8 Hz, 1H, CH-4), 3.20 (dd, J = 17.2, 1.5 Hz, 1H, CHH-3), 6.50 (d, J = 4.6 Hz, 1H, =CH-6), 7.02–7.12 (m, 2H, C6H5), 7.15–7.46 (m, 7H, C6H5), 9.95 (br. s, 1H, NH). 13C NMR (101 MHz CDCl3): δ 35.99 (CH-4), 37.16 (4-CH2), 41.85 (CH2-3), 115.89 (d,2JC-F = 21.6 Hz, CH-3′, CH-5′), 120.05 (=CH-6), 126.22 (=C-5), 126.59 (C6H5), 126.73 (d,3 JC-F = 8.0 Hz, CH-2′, CH-6′), 128.50 (C6H5), 129.50 (C6H5), 132.40 (d, 4JC-F = 3.4 Hz, C-1′), 138.32 (C6H5), 162.24 (d, 1JC-F = 247.9 Hz, C-4′), 197.71 (C=S). GC-MS (EI, 70 eV): m/z = 279 (37) [M+], 207(14), 206 (100), 173 (9), 172 (21), 146 (30), 91 (17). HRMS (ESI-TOF): m/z calcd for C18H17FNS [M+H]+, 298.1066; found: 298.1064.
(4RS)-4-Benzyl-5-(3,4-difluorophenyl)-3,4-dihydropyridine-2(1H)-thione (S9): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 8: 1, the second column: SiO2, chloroform), gave yellow solid in 95% yield. Mp. 142–149 °C (hexan: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ = 2.58 (dd, J = 13.6, 10.5 Hz, 1H, 4-CHH), 2.73–2.84 (m, 2H, CHH-3, 4-CHH), 2.92 (dddd, J = 10.5, 6.4, 4.2, 1.5, 1H, CH-4), 3.22 (dd, J = 16.8, 1.5 Hz, 1H, CHH-3), 6.51 (d, J = 4.6 Hz, 1H, =CH-6), 7.00–7.46 (m, 8H, ArH), 9.76 (s, 1H, NH). 13C NMR (101 MHz CDCl3): δ 35.93 (CH-4), 37.29 (4-CH2), 41.99 (CH2-3), 114.02 (d, 2J = 18.2 Hz, CH-2′), 117.75 (d, 2J = 17.4 Hz, CH-5′), 120.85 (d, 5J = 1.5 Hz, =CH-6), 121.06 (dd, J = 6.1, 3.4 Hz, CH-6′), 125.11 (=C-5), 126.73, 128.58, 129.51 (C6H5), 133.62 (dd, J = 5.9, 4.3 Hz, C-1′), 138.11 (C6H5), 148.41 (dd, J = 250.7, 12.6 Hz, C-3′), 150.68 (dd, J = 248.9, 12.5 Hz, C-4′), 198.1 (C=S). GC/MS (EI, 70 eV): m/z = 316 (6) [M+], 315 (27), [M+], 225 (14), 224 (100), 191 (8), 190 (20), 164 (25), 163 (6), 91 (21), 65 (7). HRMS (ESI-TOF): m/z calcd for C18H16F2NS [M+H]+, 316.0972; found: 316.0981.
(4RS)-4-Benzyl-5-(4-chlorophenyl)-3,4-dihydropyridine-2(1H)-thione (S10): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 3: 1, the second column: SiO2, chloroform), gave yellow solid in 78% yield. Mp. 161–163 °C (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.57 (dd, J = 13.6, 10.7 Hz, 1H, 4-CHH), 2.73–2.84 (m, 2H, 4-CHH, CHH-3), 2.97 (dddd, J = 10.7, 6.1, 4.0, 1.8 Hz, 1H, CH-4), 3.21 (ddd, J = 17.1, 1.8, 0.9 Hz, 1H, CHH-3), 6.55 (d, J = 4.6 Hz, 1H, =CH-6), 7.13–7.44 (m, 9H, C6H5, C6H4), 9.53 (br. s, 1H, NH). 13C NMR (101 MHz CDCl3): δ 35.78 (CH-4), 37.21 (4-CH2), 41.82 (CH2-3), 120.45 (=CH-6), 125.83 (=C-5), 126.22, 126.64, 128.54, 129.11, 129.51, 133.38, 134.73, 138.25 (C6H5, C6H4), 198.12 (C=S). GC-MS (EI, 70 eV): m/z = 313 (31) [M+], 225 (5), 224 (37), 222 (100), 221 (12), 188 (16), 162 (17), 128 (9), 115 (10), 91 (23), 65 (8). HRMS (ESI-TOF): m/z calcd for C18H17ClNS [M+H]+, 314.0770; found: 314.0782.
(4RS)-4-Benzyl-5-(3-methoxyphenyl)-3,4-dihydropyridine-2(1H)-thione (S11): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 6: 1, the second column: SiO2, chloroform), gave yellow solid in 96% yield. Mp. 137–139 °C (n-hexane: ethyl acetate). 1H NMR NMR (400 MHz, CDCl3): δ 2.57 (dd, J = 13.6, 11.0 Hz, 1H, 4-CHH), 2.78 (dd, J = 17.0, 6.7 Hz, 1H, CHH-3), 2.83 (dd, J = 13.6, 3.7 Hz, 1H, 4-CHH), 2.99 (dddd J = 11.0, 6.7, 3.7, 1.8 Hz 1H, CH-4), 3.20 (ddd, J = 17.0, 1.8, 1.0 Hz, 1H, CHH-3), 3.85 (s, 3H, OCH3), 6.56 (d, J = 4.6 Hz, 1H, =CH-6), 6.85 (ddd, J = 8.2, 2.5, 0.8 Hz, 1H, C6H4), 6.97 (t, J = 2.1 Hz, 1H, C6H4), 7.05 (ddd, J = 7.8, 1.8, 0.9 Hz, 1H, C6H4), 7.16–7.39 (m, 6H, C6H5, C6H4), 9.69 (br. d, J = 4.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 35.83 (CH-4), 37.17 (4-CH2), 41.70 (CH2-3), 55.33 (OCH3), 111.10, 112.73, 117.49 (C6H4), 120.39 (=CH-6),126.56 (C6H5), 126.84 (=C-5), 128.52, 129.57, 129.98, 137.67, 138.50, 160.06 (C6H5, C6H4), 198.07 (C=S). GC-MS (EI, 70 eV): m/z = 309 (30) [M+], 219 (15), 218 (100), 203 (6), 185 (7), 158 (14), 115 (11), 91 (17). HRMS (ESI-TOF): m/z calcd for C19H20NOS [M+H]+, 310.1266; found: 310.1252.
(4RS)-4-Benzyl-5-(3,4-dimethoxyphenyl)-3,4-dihydropyridine-2(1H)-thione (S12): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 3: 1, the second column: SiO2, chloroform), gave yellow solid in 88% yield. Mp. 135–138 °C. 1H NMR (400 MHz, CDCl3): δ 2.58 (dd, J = 13.6, 10.8 Hz, 1H, 4-CHH), 2.73–2.85 (m, 2H, 4-CHH, CHH-3), 2.97 (dddd, J = 10.8, 6.4, 3.8, 1.8 Hz, 1H, CH-4), 3.21 (ddd, J = 17.1, 1.8, 1.0 Hz, 1H, CHH-3), 3.92 (s, 3H, OCH3), 3.92 (s, 3H, OCH3), 6.50 (d, J = 4.5 Hz, 1H, CH-6), 6.87–6.93 (m, 2H, C6H3), 7.03 (dd, J = 8.3, 2.2 Hz, 1H, C6H3), 7.19–7.34 (m, 5H, C6H5), 9.76 (br. d, J = 4.5 Hz, 1H, NH). 13C NMR (100 MHz, CDCl3): δ 36.08 (CH-4), 37.24 (4-CH2), 41.78 (CH2-3), 55.99 (two OCH3), 108.28, 111.44, 117.79 (C6H3), 119.11 (=CH-6), 126.57 (C6H5), 127.18 (=C-5), 128.54, 129.01, 129.53, 138.65, 148.95, 149.26 (C6H3, C6H5), 197.42 (C=S). GC-MS (EI, 70 eV): m/z = 339 (64) [M+], 249 (16), 248 (100), 233 (7), 232 (18), 215 (77), 200 (7), 188 (13), 172 (6), 115 (8), 91 (31), 77 (4), 65 (8). HRMS (ESI-TOF): m/z calcd for C20H21NNaO2S [M+Na]+ 362.1191; found: 362.1197.
(4RS)-4-Benzyl-5-(4-fluorophenyl)-1-methyl-3,4-dihydropyridine-2(1H)-thione (S13): The crude product purified twice by column chromatography the first column (SiO2, n-hexane: ethyl acetate, 8: 1, then chloroform), gave yellow solid in 89% yield. Mp. 143–147 °C. 1H NMR (400 MHz, CDCl3): δ 2.53(dd, J = 13.7, 9.5 Hz, 1H, 4-CHH), 2.74 (dd, J = 13.7, 3.6 Hz, 1H, 4-CHH), 2.84–2.93 (m, 2H, CH-4, CHH-3), 3.29–3.39 (m, 1H, CHH-3), 3.59 (s, 3H, N-CH3), 6.57 (s, 1H, CH-6), 7.04–7.12 (m, 2H, C6H5), 7.16–7.24 (m, 3H, C6H5), 7.25– 7.30 (m, 2H), 7.35–7.44 (m, 2H, C6H5). 13C NMR (100 MHz, CDCl3): δ 36.13 (CH-4), 37.31 (4-CH2), 42.25 (N-CH3), 44.28 (CH2-3), 115.9 (d, 2JC-F = 21,8 Hz, CH-3′, CH-5′), 126.28 (d, 6J = 1.9 Hz, =CH-6), 126.54 (C6H5), 126.83 (d, 3JC-F = 8.0 Hz, CH-2′, CH-6′), 127.36 (=C-5), 128.39 (2C), 129.55 (2C, C6H5), 132.40 (d, 4JC-F = 3.3 Hz, C-1′), 138.42 (C6H5), 162.28 (d, 1JC-F = 248.0 Hz, C-4′), 195.56 (C=S). GC/MS GC-MS (EI, 70 eV): m/z = 311 (20) [M+], 220 (100), 146 (15), 91 (44). HRMS (ESI-TOF): m/z calcd for C19H19FNS [M+H]+, 312.1222; found: 312.1216.
(4RS)-4-Benzyl-5-(3,4-difluorophenyl)-1-methyl-3,4-dihydropyridine-2(1H)-thione (S14): The crude product purified twice by column chromatography the first (SiO2, n-hexane: ethyl acetate, 10: 1, then chloroform), gave yellow solid in 96% yield. Mp. 128–132 °C. 1H NMR (400 MHz, CDCl3): δ 2.55 (dd, J = 13.4, 9.7 Hz, 1H, 4-CHH), 2.73 (dd, J = 13.4, 3.9 Hz, 1H, 4-CHH), 2.81–2.87 (m, 1H, CH-4), 2.90 (dd, J = 15.1, 6.6 Hz, 1H, CHH-3), 3.36 (d, J = 15.1 Hz, 1H, CHH-3), 3.59 (s, 3H, NCH3), 6.59 (s, 1H, =CH-6), 7.07–7.33 (m, 8H, C6H5). 13C NMR (100 MHz, CDCl3): δ 36.03 (CH-4), 37.43 (4-CH2), 42.29 (N-CH3), 44.40 (CH2-3), 114.09 (d, 2J = 18.2 Hz, CH-2′), 117.74 (d, 2J = 17.5 Hz, CH-5′), 121.13 (dd, J = 6.2, 3.3 Hz, CH-6′), 126.20 (=C-5), 126.66 (C6H5), 127.02 (=CH-6), 128.45, 129.53 (C6H5), 133.62 (dd, J = 6.2, 3.8 Hz, C-1′), 138.21 (C6H5), 149.66 (dd, J = 249.9, 13.8 Hz, C-3′), 150.53 (dd, J = 248.6, 13.2 Hz, C-2′), 195.97 (C=S). GC-MS (EI, 70 eV): m/z = 329 (23) [M+], 238 (100), 164 (10). HRMS (ESI-TOF): m/z calcd. for C19H17F2NNaS [M+Na]+ 352.0947; found: 352.0946.
(4RS)-4-Benzyl-5-(4-chlorophenyl)-1-methyl-3,4-dihydropyridine-2(1H)-thione (S15): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 10: 1, the second column SiO2, chloroform), gave yellow solid in 84% yield. Mp. 154–156 °C. 1H NMR (400 MHz, CDCl3): δ 2.53 (dd, J = 13.5, 9.8 Hz, 1H, 4-CHH), 2.67–2.79 (m, 1H, CHH-3), 2.84–3.00 (m, 2H, CH-4, 4-CHH), 3.22–3.43 (m, 1H, CHH-3), 3.58 (s, 3H, NCH3), 6.62 (s, 1H, =CH-6), 7.17–7.23 (m, 3H, C6H5), 7.25–7.31 (m, 2H, C6H5), 7.35 (s, 4H, C6H4). 13C NMR (100 MHz, CDCl3): δ 35.84 (CH-4), 37.35 (4-CH2), 42.27 (NCH3), 44.27 (CH2-3), 126.31, 126.57 (ArH), 126.66 (=CH-6), 126.95 (=C-5), 128.40, 129.10 (ArH), 129.54 (ArH), 133.39, 134.75, 138.34 (Ar), 195.82 (C=S). GC-MS (EI, 70 eV): m/z = 327 (23) [M+], 239 (5), 238 (38), 236 (100), 235 (7), 201 (6), 128 (6), 115 (6), 91 (10), 65 (5). HRMS (ESI-TOF): m/z calcd. for C19H18ClNNaS [M+Na]+ 350.0746; found: 350.0755.
(4-RS)-4-Benzyl-5-(3-methoxyphenyl)-1-methyl-3,4-dihydropyridine-2(1H)-thione (S16): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 10: 1, the second column: SiO2, chloroform), gave yellow solid in 98% yield. Mp. 106–109 °C (hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.53 (dd, J = 13.5, 10.2 Hz, 1H, 4-CHH), 2.79–2.94 (m, 3H, CH-4, 4-CHH, CHH-3), 3.24–3.40 (m, 1H, CHH-3), 3.58 (s, 3H, NCH3), 3.85 (s, 3H, OCH3), 6.64 (s, 1H, =CH-6), 6.86 (ddd, J = 8.2, 2.5, 0.8 Hz, 1H, ArH), 6,97 (t, J = 2.1 Hz, 1H, ArH), 7.05 (ddd, J = 7.8, 1.8, 0.9 Hz, 1H, ArH), 7.16–7.37 (m, 6H, ArH). 13C NMR (100 MHz, CDCl3): δ = 35.94 (CH-4), 37.33 (4-CH2), 42.27 (NCH3), 44.18 (CH2-3), 55.33 (O-CH3), 111.25, 112.68, 117.57 (ArH), 126.48 (=C-6), 126.61 (ArH), 127.98 (=C-5), 128.37, 129.61, 129.96 (ArH), 137.68, 138.57, 160.06 (Ar), 195.81 (C=S). GC-MS (EI, 70 eV): m/z = 323 (21) [M+], 233 (15), 232 (100), 217 (5), 189 (7), 158 (8), 115 (7), 91 (9). HRMS (ESI-TOF): m/z calcd. for C20H21NnaOS [M+Na]+ 346.1242; found: 346.1236.
(4RS)-4-Benzyl-5-(3,4-dimethoxyphenyl)-1-methyl-3,4-dihydropyridine-2(1H)-thione (S17): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 3: 1, the second column SiO2, chloroform), gave yellow solid in 98% yield. Mp. 115–119 °C (n-hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.54 (dd, J = 13.6, 9.9 Hz, 1H, 4-CHH), 2.77 (dd, J = 13.6, 3.4 Hz, 1H, 4-CHH), 2.82–3.03 (m, 2H, CHH-3, CH-4), 3.25–3.46 (m, 1H, CHH-3), 3.61 (s, 3H, NCH3), 3.92 (d, J = 4.6 Hz, 6H, two OCH3), 6.56 (s, 1H, =CH-6), 6.85–6.95 (m, 2H, C6H3), 7.03 (dd, J = 8.3, 2.2 Hz, 1H, C6H3), 7.12–7.48 (m, 5H, C6H5). 13C NMR (100 MHz, CDCl3): δ 36.22 (CH-4), 37.38 (4-CH2), 42.29 (N-CH3), 44.23 (CH2-3), 56.00 (two OCH3), 108.32, 108.36, 111.42, 117.91 (C6H3), 125.33 (=CH-6), 126.50 (C6H5), 128.38 (C6H3), 128.43 (C6H5), 128.98 (=C-5), 129.57 (C6H5), 138.74 (C6H5), 148.98, 149.24 (C6H3), 195.17 (C=S). GC-MS (EI, 70 eV): m/z = 353 (38) [M+], 264 (6), 263 (17), 262 (100), 247 (5), 246 (18), 231 (6), 206 (4), 188 (9), 115 (4), 91 (10). HRMS (ESI-TOF): m/z calcd. for C21H23NNaO2S [M+Na]+ 376.1347; found: 376.1340.
(4RS)-4-(Naphthalen-1-ylmethyl)-5-phenyl-3,4-dihydropyridine-2(1H)-thione (S18): The crude product purified twice by column chromatography (the first column SiO2, n-hexane: ethyl acetate, 6: 1, the second column SiO2, chloroform), gave yellow solid in 68% yield. Mp. 160–162 °C (n-hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.78 (dd, J = 16.9, 7.1 Hz, 1H, CHH-3), 2.89 (dd, J = 12.1, 3.0 Hz, 1H, 4-CHH), 3.22 (d, J = 16.9 Hz, 1H, CHH-3), 3.26–3.32 (m, 2H, 4-CHH, CH-4), 6.55 (d, J = 4.5, 1H, =CH-6), 7.29–7.55 (m, 9H, ArH), 6.67–7.77 (m, 1H, ArH), 7.80–7.98 (m, 2H, ArH), 9.54 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ 34.18 (CH2–4), 34.48 (4-CH), 42.21 (CH2-3), 120.26 (=CH-6), 123.61, 125.51, 125.79, 125.92, 127.41, 127.91 (C10H7, C6H5), 128.02 (=C-5), 128.74, 128.95, 128.97, 131.69, 134.01, 134.19, 136.41 (C10H7, C6H5, two signal overlapped), 198.14 (C=S). GC-MS (EI, 70 eV); m/z = 330 (5), 329 (20), [M+], 189 (15), 188 (100), 187 (34), 154 (15), 142 (7), 141 (28), 128 (25), 127 (10), 115 (18). HRMS (ESI-TOF): m/z calcd. for C22H20NS [M+H]+ 330.1316; found: 330.1318.
(4RS)-4-(4-Methoxybenzyl)-5-phenyl-3,4-dihydropyridine-2(1H)-thione (S19): The crude product purified twice by column chromatography (the first column SiO2, n-hexane: ethyl acetate, 10: 1, the second column SiO2 chloroform), gave yellow solid in 86% yield. Mp. 149–151 °C (n-hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.52 (dd, J = 13.9, 11.0 Hz, 1H, 4-CHH), 2.70–2.89 (m, 2H, 4-CHH, CHH-3), 2.96 (dddd, J = 11.0, 6.9, 3.7, 1.9 Hz, 1H, 4-CH), 3.21 (ddd, J = 17.0,1.9, 1.0 Hz, 1H, CHH-3), 3.79 (s, 3H, OCH3), 6.55 (d, J = 4.6 Hz, 1H, =CH-6), 6.73–6.97 (m, 2H, C6H4), 7.04–7.21 (m, 2H, C6H4), 7.27–7.35 (m, 1H, C6H5), 7.36–7.50 (m, 4H, C6H5), 9.73 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ 35.90 (CH-4), 36.26 (4-CH2), 41.69 (CH2-3), 55.28 (OCH3), 113.91 (ArH), 120.10 (=CH-6), 124.97 (ArH), 127.09 (=C-5), 127.69, 128.98, 130.54, 130.55, 136.23, 158.32 (ArH, Ar), 198.01 (C=S). GC-MS (EI, 70 eV); m/z = 309 (13), [M+], 189 (7), 188 (43), 187 (23), 154 (12), 128 (17), 121 (100), 115 (5), 91 (5), 77 (8). HRMS (ESI-TOF): m/z calcd. for C19H20NOS [M+H]+ 310.1266; found: 310.1267.
4-([1,1′-Biphenyl]-4-ylmethyl)-5-phenyl-3,4-dihydropyridine-2(1H)-thione (S20): Yield 98%. The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 6: 1, the second column: SiO2, chloroform), gave yellow solid in 98% yield. Mp. 173–174 °C. 1H NMR (400 MHz, DMSO-d6): δ 2.43 (dd, J = 13.6, 11.2 Hz, 1H, 4-CHH), 2.67–2.82 (m, 2H, 4-CHH, 3-CHH), 2.91 (ddd, J = 17.0, 1.9, 1.0 Hz, 1H, CHH-3), 3.04–3.12 (m, 1H, CH-4), 6.75 (d, J = 4.6 Hz, 1H, =CH-6), 7.21–7.55 (m, 8H, ArH), 7.54–7.79 (m, 6H, ArH), 11.67 (d, J = 4.6 Hz, 1H, NH). 13C NMR (100 MHz, DMSO-d6): δ 34.06 (CH-4), 36.09 (4-CH2) 41.90 (CH2-3), 120.97 (=CH-6), 124.51 (Ar), 124.83 (=C-5), 126.42, 126.43, 126.95, 127.16, 128.75, 128.80, 129.89, 135.91, 137.77, 138.10, 139.84 (Ar), 196.37 (C=S). GC-MS (EI, 70 eV); m/z = 355 (15), [M+], 281 (8), 208, 207 (24), 189 (15), 188 (100), 187 (25), 168 (7), 154 (17), 128 (25), 127 (11). Anal. calcd for C24H21NS: C 81.09, H 5.95, N 3.94, S 9.02. Found: C 80.98, H 5.90, N 4.04.
(4RS)-4-Benzyl-5-(naphthalen-1-yl)-3,4-dihydropyridine-2(1H)-thione (S21): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate, 6: 1, the second column SiO2, chloroform), gave yellow solid in 95% yield. Mp. 173–175 °C (n-hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3): δ 2.55 (dd, J = 13.5, 11.4 Hz, 1H, 4-CHH), 2.76 (dd, J = 13.5, 3.8 Hz 1H, 4-CHH), 2.95 (dddd, J = 11.4, 6.6, 3.8, 3.4 Hz, 1H, CH-4), 3.08 (dd, J = 17.0, 6.6 Hz, 1H, CHH-3) 3.20 (dd, J = 17.0, 3.4 Hz, 1H, CHH-3), 6.27 (d, J = 4.4 Hz, 1H, =CH-6), 7.02–7.07 (m, 2H, C6H5), 7.11–7.23 (m, 3H, C6H5), 7.34 (dd, J = 7.0, 1.3 Hz, 1H, C10H7), 7.48 (dd, J = 8.3, 7.0 Hz, 1H, C10H7), 7.51–7.56 (m, 2H, C10H7), 7.86 (dt, J = 8.4, 1.0 Hz, 1H, C10H7), 7.89–7.95 (m, 2H, C10H7), 9.43 (s, 1H, NH). 13C NMR (100 MHz, CDCl3): δ 36.94 (4-CH2), 38.89 (CH-4), 41.91 (CH2-3), 123.00 (=CH-6), 125.08, 125.35, 126.10, 126,40, 126.48, 126.75 (C10H7), 127.56 (=C-5), 128.39, 128.49 (C6H5), 128.69 (C10H7), 129.43 (C6H5), 131.80, 133.90, 135.73 (C10H7), 138.27(C6H5), 198.39 (C=S). GC-MS (EI, 70 eV): m/z = 330 (7), 329 (28), [M+], 240 (6), 239 (19), 238 (100), 221 (9), 205 (22), 204 (35), 179 (10), 178 (21), 152 (10), 91 (18). HRMS (ESI-TOF): m/z calcd. for C22H19NNaS [M+Na]+ 352.1136; found: 352.1132.
(4RS)-4-Benzyl-5-(thiophen-2-yl)-3,4-dihydropyridine-2(1H)-thione (S22): The crude product purified twice by column chromatography (the first column: SiO2, n-hexane: ethyl acetate), 10:1, the second column SiO2, chloroform), gave yellow solid in 95% yield. Mp. 130–132 °C (n-hexane: ethyl acetate). 1H NMR (400 MHz, CDCl3) δ 2.60 (dd, J = 14.9, 12.0 Hz, 1H, 4-CHH), 2.78 (dd, J = 17.1, 6.9 Hz, 1H, CHH-3), 2.85–2.97 (m, 2H, 4-CHH, CH-4), 3.19 (d, J = 17.1 Hz, 1H, CHH-3), 6.58 (d, J = 4.5 Hz, 1H, =CH-6), 7.03 (dd, J = 5.1, 3.6 Hz, 1H, C4H3S), 7.08 (dd, J = 3.7, 1.2 Hz, 1H, C4H3S), 7.20–7.28 (m, 4H, C4H3S, C6H5), 7.29–7.35 (m, 2H, C6H5), 9.78 (s, 1H, NH). 13C NMR (101 MHz, CDCl3) δ 37.28 (CH-4), 37.32 (4-CH2), 41.53 (CH2-3), 118.82 (=CH-6), 122.05 (=C-5), 122.96, 124.20 (C4H3S), 126.62 (C6H5), 127.91 (C4H3S), 128.55 (2C, C6H5), 129.58 (2C, (C6H5), 138.43 ((C6H5), 140.61 (C4H3S), 197.42 (C=S). GC-MS (EI, 70 eV): m/z = 285 (48), [M+], 195 (13), 194 (100), 193 (14), 161 (23), 134 (30), 91 (21). HRMS (ESI-TOF): m/z calcd. for C16H16NS2 [M+H]+ 286.0724; found: 286.0724.