Month 2014
Thiadiazines
2-Pyrrolidino-5-(4-bromophenyl)-6H-1,3,4-thiadiazine.
Hydrobromide 3b: prepared from 1.45g (10 mmol) of 2a and
2.78 g (10mmol) of 4-bromo-phenacylbromide 1b. Yield: 2.92 g
(72%), yellow prisms (EtOH), mp 129°C; ir (KBr, cmÀ1): 3093
(m), 3050 (m), 2972 (m), 2843 (m), 1619 (m), 1584 (s), 1448 (m),
1412 (m), 1317 (m), 852 (m), 811 (m); 1H nmr (DMSO-d6,
300 MHz): δ = 2.04 (m, 4H, 2xCH2), 3.41–3.45 (t, 4H, 2xN-CH2),
4.31 (s, 2H, 6-CH2, thiadiazine), 7.64–7.88 (m, 4H, ArH), 13.00
(s, 1H, NH+); 13C nmr (DMSO-d6, 75MHz): δ = 27.18, 125.34
(ArH), 129.12 (ArH), 132.38 (Ar), 149.37 (5-C, thiadiazine),
158.84 (2-C, thiadiazine); ms (El, 70eV): m/z (%) = 28 (49), 73
(39), 102 (15), 113 (100), 141 (2), 183 (2), 279 (4), 323/325 (M+,
10/10). Anal. Calcd. for C13H15Br2N3S (405.15): C, 38.54 H, 3.73
N, 10.37. Found: C, 38.87, H, 3.98 N, 10.27. Free base 4b:
Yield: 2.43g (75%), yellow prisms (EtOH), mp 157°C; ir (KBr,
cmÀ1): 2968 (m), 2868 (m), 1586 (m), 1531 (m), 1502 (s), 1482
(s), 1457 (m), 1409 (m), 1368 (m), 1330 (m), 1069 (m), 1002 (m),
2872 (m), 1597 (m), 1505 (s), 1484 (5), 1458 (s), 1371 (m),
1319 (m), 1222 (m), 1170 (m), 1156 (m), 918 (m), 841 (m), 572
(m); H nmr (CDCl3, 300 MHz): δ = 1.96–2.00 (m, 4H, 2xCH2),
1
3.53 (s, 2H, 6-CH2, thiadiazine), 3.63–3.68 (t, 4H, 2xN-CH2),
7.07–7.89 (m, 4H, ArH); 13C nmr (CDCl3, 50MHz): δ = 21.58
(6-CH2, thiadiazine), 24.92 (2xCH2), 48.16 (2xCH2), 115.75
(d, J(C,F) = 21.2, ArH), 128.24 (d, J(C,F) = 8.1, ArH), 132.26
(d, J(C,F) = 3.3, Ar), 148.51 (5-C, thiadiazine), 160.898(d, J(C,
F) = 247.3, Ar), 165.85 (2-C, thiadiazine); ms (El, 70 eV): m/z
(%) = 41 (1), 55 (14), 73 (29), 113 (100), 121 (16), 141 (4),
165 (2), 203 (3), 230 (6), 231 (9), 263 (M+, 17). Anal. Calcd.
for C13H14FN3S (263.33): C, 59.29; H, 5.36; N, 15.96. Found:
C, 59.12; H, 5.32; N, 15.91.
2-Pyrrolidino-5-(4-tolyl)-6H-1,3,4-thiadiazine. Hydrochloride
3e: prepared from 1.45 g (10 mmol) 2a and 2.13 g (10 mmol) of
4-methyl-phenacylbromide 1e. Yield: 2.3 g (78%), yellow
prisms (EtOH), mp 175°C; ir (KBr, cmÀ1): 3036 (m), 2969 (s),
2875 (m), 2813 (s), 1584 (s), 1447 (m), 1413 (m), 1324 (m),
1183 (m), 1153 (m), 915 (m), 807 (m), 742 (m); 1H nmr
(DMSO-d6, 300 MHz): δ = 2.04 (s, 3H, Me), 2.46–2.52 (m, 4H,
2xCH2), 3.70–3.74 (t, 4H, 2xN-CH2), 4.31 (s, 2H, 6-CH2,
thiadiazine) 7.36–7.84 (m, 4H, ArH), 12.92 (s, 1H, NH+);
ms (El, 70 eV): m/z (%) = 36 (53), 55 (22), 73 (42), 113
(100), 117 (16), 161 (4), 162 (1), 230 (6), 259 (M+, 72).
Anal. Calcd. for C14H18Cl N3S (295,83): C, 56.84; H, 6.13;
N, 14.20. Found: C, 52.43; H, 5.62; N, 10.84. Free base
4e: Yield: 1.97 g (76%), yellow prisms (EtOH), mp. 142°C;
ir (KBr, cmÀ1): 3030 (m), 2966 (m), 2921 (m), 2874 (m),
1503 (s), 1474 (s), 1455 (s), 1416 (m), 1366 (s), 1322 (s),
1226 (m), 1193 (m), 913 (m), 815 (m), 574 (m); 1H nmr
(CDCl3, 300 MHz): δ = 1.95–1.99 (m, 4H, 2xCH2), 2.38 (s,
3H, Me), 3.53 (s, 2H, 6-CH2, thiadiazine), 3.60–3.67 (t, 4H,
2xN-CH2), 7.77–7.80 (m, 4H, ArH); 13C nmr (DMSO-d6,
50 MHz) δ = 21.22 (Me), 21.58 (6-CH2, thiadiazine), 24.92
(2xCH2), 48.05 (2xCH2), 126.22 (ArH), 129.19 (ArH),
133.21 (Ar), 139.27 (Ar), 145.29 (5-C, thiadiazine), 148.37
(2-C, thiadiazine); ms (El, 70 eV): m/z (%) = 28 (42), 55
(25), 73 (41), 113 (100), 117 (15), 161 (3), 230 (5), 259
(M+, 79). Anal. Calcd. for C14H17N3S (259.37): C, 64.83;
H, 6.61; N, 16.20. Found: C, 64.53; H, 6.59; N, 16.18.
2-Pyrrolidino-5-(4-methoxyphenyl)-6H-1,3,4-thiadiazine.
Hydrochloride 3f: prepared from 1.45g (10 mmol) of 2a and
2.29g (10 mmol) of p-methoxy-phenacylbromide 1f. Yield:
2.30g (74%), yellow prisms (EtOH), mp 171°C; ir (KBr, cmÀ1):
3419 (m), 2978 (m), 2836 (m), 1603 (s), 1582 (s), 1514 (m),
1460 (m), 1447 (m), 1424 (m), 1315 (s), 1255 (s), 1181 (m),
1009 (m), 847 (m), 587 (m); 1H nmr (DMSO-d6, 300MHz):
δ = 2.03 (m, 4H, 2xCH2), 3.73 (t, 4H, 2xN-CH2), 3.85 (s, 3H,
MeO), 4.29 (s, 2H, 6-CH2, thiadiazine), 7.10–7.91 (m, 4H, ArH),
13.12 (s, 1H, NH+); 13C nmr (DMSO-d6, 50 MHz): δ = 22.16
(6-CH2, thiadiazine), 24.61 (2xCH2), 51.19 (2xCH2), 114.39
(ArH), 125.07 (Ar), 128.67 (ArH), 150.21 (5-C, thiadiazine), 158.58
(2-C, thiadiazine), 161.74 (OAr); ms (El, 70eV): m/z (%) = 28
(7), 55 (23), 73 (47), 113 (100), 133 (49), 177 (4), 215 (1), 243
(6), 275 (M+, 57). Anal. Calcd. for C14H18ClN3OS (311,83): C,
53.92; H, 5.82; N, 13.48. Found: C, 53.79; H, 5.81; N, 13.47.
2-Pyrrolidino-5-(4-nitrophenyl)-6H-1,3,4-thiadiazine.
Hydrobromide 3g: prepared from 1.45 g (10 mmol) of 2a and
2.44 g (10 mmol) of p-nitro-phenacylbromide 1g. Yield: 2.67g
(72%), yellow prisms (EtOH), mp 211°C; ir (KBr, cmÀ1): 2974
(m), 2822 (m), 1620 (m), 1598 (m), 1575 (s), 1521 (s), 1449
(m), 1415 (m), 1348 (s), 1313 (m), 860 (m), 751 (m); 1H nmr
1
915 (m), 943 (m); H nmr (CDCl3, 300 MHz): δ = 1.96–2.00 (m,
4H, 2xCH2), 3.52 (s, 2H, 6-CH2), 3.63–3.68 (t, 4H, 2xN-CH2),
7.52–7.77 (m, 4H, ArH); ms (El, 70eV): m/z (%) = 28 (23), 55
(46), 102 (21), 113 (100), 142 (2), 183 (7), 293 (1), 323/325 (M+,
15/16). Anal. Calcd. for C13H14BrN3S (324,24): C, 48.16; H,
4.35; N, 12.96. Found: C, 48.42; H, 4.56; N, 13.06.
2-Pyrrolidino-5-(4-chlorophenyl)-6H-1,3,4-thiadiazine.
Hydrobromide 3c: prepared from 1.45g (10 mmol) 2a and 1.89 g
(10 mmol) of 4-chloro-phenacylbromide 1c. Yield: 2.56g (71%),
yellow prisms (EtOH), mp 223°C; ir (KBr, cmÀ1): 3050 (m),
2973 (m), 2841 (m), 1620 (m), 1584 (s), 1449 (m), 1413 (m),
1317 (m), 1093 (m), 854 (m), 815 (m), 707 (m); 1H nmr
(DMSO-d6, 300MHz): δ = 2.04 (m, 4H, 2xCH2), 3.70–3.74 (t,
4H, 2xN-CH2), 4.31 (s, 2H, 6-CH2, thiadiazine), 7.64–7.95 (m,
4H, ArH), 13.02 (s, 1H, NH+); ms (El, 70eV): m/z (%)= 41 (24),
55 (32), 73 (47), 113 (100), 137 (8), 148 (5), 193 (1), 250 (3),
279 (M+, 28). Anal. Calcd. for C13H15BrClN3S (360.70): C,
43.29 H, 4.19 N, 11.65. Found: C, 43.53 H,4.29,N, 11.63. Free
base 4c: Yield: 1.93 g (69%), yellow prisms (EtOH), mp 139°C;
ir (KBr, cmÀ1): 2967 (m), 2874 (m), 1536 (m), 1507 (s), 1473
(s), 1454 (s), 1412 (m), 1366 (s), 1325 (m), 1218 (m), 1191 (m),
1089 (m), 915 (m), 836 (m), 812 (m); 1H nmr (CDCl3,
300 MHz): δ = 1.96–2.01 (m, 4H, 2xCH2), 3.52 (s, 2H, 6-CH2,
thiadiazine), 3.63–3.68 (t, 4H, 2xN-CH2), 7.37–7.84 (m, 4H,
ArH); 13C nmr (CDCl3, 75MHz): δ = 21.48 (6-CH2, thiadiazine)
25.01 (CH2), 48.21 (CH2), 127.59 (ArH), 134.66 (ArH), 135.66
(Ar), 144.19 (5-C, thiadiazine), 148.51 (2-C, thiadiazine); ms (El,
70er): m/z (%) = 28 (7), 55 (26), 73 (48), 113 (100), 137 (9), 139
(3), 181 (1), 250 (3), 279 (M+, 26). Anal. Calcd. for
C13H14ClN3S (279.79): C, 55.81; H, 5.04; N, 15.02. Found: C,
55.92; H, 5.03; N, 14.97.
2-Pyrrolidino-5-(4-fluorophenyl)-6H-1,3,4-thiadiazine.
Hydrobromide 3d: prepared from 1.45 g (10 mmol) of 2a and
2.17 g (10mmol) of 4-fluoro-phenacylbromide 1d. Yield: 2.51 g
(73%), yellow prisms (EtOH), mp 224°C; ir (RBr, cmÀ1): 3038
(m), 2978 (m), 2833 (m), 1621 (m), 1595 (s), 1513 (m), 1449
(m), 1416 (m), 1320 (m), 1232 (m), 1158 (m), 854 (m), 812 (m),
735 (m), 577 (m); 1H nmr (DMSO-d6, 300MHz): δ = 2.04 (m,
4H, 2xCH2), 3.38–3.45 (t, 4H, 2xN-CH2), 4.30 (s, 2H, 6-CH2,
thiadiazine), 7.39–8.00 (m, 4H, ArH), 12.93 (s, 1H, NH+); ms
(El, 70eV): m/z (%) = 51 (6), 76 (13), 102 (35), 137 (17), 160
(21), 187 (51), 290 (3), 325 (M+, 100). Anal. Calcd. for
C15H15BrFN3S (344.25): C, 45.36; H, 4.39; N, 12.21. Found: C,
45.29; H, 4.37; N, 12.20. Free base 4d: Yield: 1.89 g (72%),
colourless prisms (EtOH), mp 214°C. IR (KBr, cmÀ1): 2986 (m),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet