Month 2014
Diastereoselective Synthesis of Novel Pyrrolidine or Pyrrolizine-Fused Benzo-d-sultams
via 1,3-Dipolar Cycloadditions
1H NMR (500 MHz, CDCl3): d 2.37 (s, 3H, MeN), 2.55–2.59
( m, 1H, CHN), 3.41 (s, 3H, MeNSO2), 3.54–3.58 (m, 1H,
CHN), 3.71(d, J = 8.8 Hz, 1H, ArCHN), 4.13–4.21 (m, 2H,
CHSO2, CHPh), 7.17–7.40 (m, 9H, Ar); 13C NMR
(125 MHz, CDCl3): d 33.0, 39.8, 47.3, 63.7, 70.3, 71.4,
120.3, 125.1, 127.6, 127.8, 128.4, 129.2, 130.2, 131.1,
140.1, 143.0; ms: m/z (%) 328 (2) [M+], 220 (62), 144
(100), 133 (97), 117 (42).
142.0; ms: m/z (%) 342 (4) [M+], 234 (28), 158 (93), 144
(97), 133 (100).
5-Ethyl-1,3-diphenyl-1,2,3,3a,5,9b-hexahydrobenzo[c]pyrrolo
[2,3-e][1,2]thiazine-4,4-dioxide (5g). White solid; yield: 49%;
1
mp: 229–231ꢀC; IR (KBr) 1319 (ÀSO2), 1133 (ÀSO2) cmÀ1; H
NMR (500 MHz, CDCl3): d 1.41 (t, J = 7.1 Hz, 3H, MeCN),
3.55–3.57 (m, 1H, CHN), 3.85–3.99 (m, 1H, CHN), 4.00–4.10
(m, 3H, MeCH2N, CHPh), 4.55 (dd, J= 8.6, 11.5 Hz, 1H, CHSO2),
5.45 (d, J= 8.6 Hz, 1H, ArCHN), 6.67–7.43 (m, 14H, Ar); 13C NMR
(125 MHz, CDCl3): 21.6, 30.8, 45.7, 56.4, 61.6, 68.9, 112.6, 118.3,
119.0, 122.0, 128.1, 128.3, 128.5, 129.4, 129.9, 130.3,136.0 136.8,
137.5, 147.7; ms: m/z (%) 404 (3) [M+], 167 (32), 149 (100), 130
(50), 57 (92).
1,5-8-Trimethyl-3-phenyl-1,2,3,3a,5,9b-hexahydrobenzo[c]
pyrrolo[2,3-e][1,2]thiazine-4,4-dione (5b). White solid; yield:
69%; mp: 165–167ꢀC; IR (KBr) 1293 (ÀSO2), 1128 (ÀSO2)
1
cmÀ1; H NMR (500 MHz, CDCl3): d 2.30 (s, 3H, MeN), 2.40
(s, 3H, MePh), 2.54–2.58 (m, 1H, CHN), 3.39 (s, 3H, MeNSO2),
3.55–3.58 (m, 1H, CHN), 3.65 (d, J = 8.5 Hz, 1H, ArCHN),
4.13–4.17 (m, 2H, CHSO2, CHPh), 7.06–7.44 (m, 8H, Ar);
13C NMR (125 MHz, CDCl3): d 21.3, 33.5, 39.9, 47.3, 63.7,
70.5, 71.4, 120.6, 127.5, 127.7, 128.4, 129.2, 130.7, 131.8,
134.9, 140.2, 140.4; ms: m/z (%) 342 (1) [M+], 277 (7), 234
(61), 158 (100), 144 (62).
General procedure for the preparation of 5h–j. A mixture of
proline (1.0 mmol) and 2-formylphenyl (E)-N-(2-formylphenyl)-
N-alkyl-2-phenylethenesulfonamides (1.0 mmol) in dry toluene
(30 mL) containing molecular sieves (500 mg, 4 Ǻ) was heated
at reflux with stirring for 12 h. The solvent was then removed
under reduced pressure, and the residue was subjected to plate
chromatography using hexane-EtOAc (3:1) to give 5h–j.
8-Methoxy-1,5-dimethyl-3-phenyl-1,2,3,3a,5,9b-hexahydrobenzo
[c]pyrrolo[2,3-e][1,2]thiazine-4,4-dione (5c). White solid; yield:
75%; mp: 181–183ꢀC; IR (KBr) 1308 (ÀSO2), 1128 (ÀSO2) cmÀ1
;
5-Methyl-7-phenyl-5,7,7a,8,9,10-hexahydrobenzo[3,4][1,2]
thiazino[6,5-b]pyrrolizin-11-ium-6-olate 6-oxide (5h). White
solid; yield: 59%; mp: 200–202ꢀC; IR (KBr) n 1314 (ÀSO2);
1H NMR (500 MHz, CDCl3): d 2.32 (s, 3H, MeN), 2.53–2.57
(m, 1H, CHN), 3.40 (s, 3H, MeNSO2), 3.55–3.59 (m, 1H, CHN),
3.64 (d, J=8.4Hz, 1H, ArCHN), 3.85 (s, 3H, MeNSO2), 4.11–4.18
( m, 2H, CHSO2, CHPh), 6.83–7.42 (m, 8H, Ar); 13C NMR
(125 MHz, CDCl3): d 35.1, 39.9, 47.4, 56.0, 63.8, 70.8,
71.4, 114.3, 117.6, 123.0, 127.7, 128.4, 129.2, 129.61,
136.1, 140.3, 157.3; ms: m/z (%) 358 (3) [M+], 250 (41),
174 (100), 160 (44), 133 (88).
;
1127 (ÀSO2) cmÀ1 1H NMR (500MHz, CDCl3): d 1.22–1.24
(1H, m, CHCH2CH2N), 1.38–1.41 (1H, m, CH2CH2CH2N),
1.76–1.78 (1H, m, CH2CHCH2N ), 1.88–1.91 (1H,m,
CH2CHCH2N), 2.88–2.90 (1H, m, CHN), 3.33 (3H, s,
MeN), 3.43–3.45 (1H, m, CHN), 3.91 (1H, m, NCHCPh),
4.03 (1H, dd, J = 10.9, 8.5 Hz, CHPh), 4.50 (1H, dd,
J = 10.9, 8.3 Hz, CHSO2), 4.59 (1H, d, J = 8.3 Hz, ArCHN),
7.05–7.68 (9H, Ar); 13C NMR (125 MHz, CDCl3) 26.1,
29.1, 31.7, 49.4, 56.8, 61.9, 67.8, 69.1, 118.0, 118.2,
124.9, 127.4, 128.1, 129.0, 129.2, 129.5, 137.6, 140.0;
ms: m/z (%) 354 (1) [M+], 290 (30), 247(41), 220 (92),
144(100).
5-Methyl-1,3-diphenyl-1,2,3,3a,5,9b-hexahydrobenzo[c]
pyrrolo[2,3-e][1,2]thiazine (5d). White solid; yield: 51%; mp:
236–238ꢀC; IR (KBr) 1316 (ÀSO2), 1133 (ÀSO2) cmÀ1
;
1H
NMR (500 MHz, CDCl3): d 3.30 (s, 3H, MeN), 3.51–3.5 (m, 1H,
CHN), 3.95–4.11 (2H, m, CHN, CHPh), 4.47–4.55 (dd, J = 8.5,
9.7 Hz, 1H, CHSO2), 5.45 (1H, d, J = 8.5, ArCHN), 6.63–7.37
(14H, Ar); 13C NMR (125 MHz, CDCl3) d 30.1, 45.2, 55.9, 61.0,
68.5, 112.3, 118.1, 118.3, 125.3, 127.6, 127.7, 127.9, 128.9,
129.0, 129.4, 129.5, 137.0, 138.9, 146.7; ms: m/z (%) 388 (5)
[M+], 195 (93), 144 (100), 130(26).
2,5-Dimethyl-7-phenyl-5,7,7a,8,9,10-hexahydrobenzo[3,4]
[1,2]thiazino[6,5-b]pyrrolizin-11-ium-6-olate 6-oxide (5i).
White solid; yield: 60%; mp: 225–227ꢀC; IR (KBr) 1306
;
(ÀSO2); 1133 (ÀSO2) cmÀ1 1H NMR (500 MHz, CDCl3): d
1.22–1.24 (1H, CHCH2CH2N), 1.38–1.41 (1H, m, CHCH2CH2N),
1.76–1.78 (1H, m, CH2CHCH2N), 1.88–1.91 (1H, m,
CH2CHCH2N), 2.41 (3H, s, Me-Ph), 2.88–2.90 (1H, m, CHN),
3.31 (3H, s, MeN), 3.44–3.46 (1H, m, CHN), 3.92–3.93 (1H, m,
CHN), 4.03 (1H, dd, J= 10.8, 8.5 Hz, CHPh), 4.50 (1H, dd,
J = 10.8, 8.4 Hz, CHSO2), 4.56 (1H, d, J = 8.4 Hz, ArCHN),
6.96–7.4 (8H, Ar); 13C NMR (125 MHz, CDCl3): d 21.40,
26.2, 29.1, 32.1, 49.40, 56.92, 61.2, 67.9, 69.9, 118.3, 127.4,
128.1, 128.9, 129.8, 129.9, 134.7, 137.2, 137.7, 149.8; ms: m/z
(%) 368 (1.5) [M+), 234 (41), 158 (100), 149 (65), 69 (96).
5,8-Dimethyl-1,3-diphenyl-1,2,3,3a,5,9b-hexahydrobenzo[c]
pyrrolo[2,3-e][1,2]thiazine-4,4-dioxide (5e). White solid; yield:
56%; mp: 229–231ꢀC; IR (KBr) 1320 (ÀSO2), 1133
(ÀSO2) cmÀ1
;
1H NMR (500 MHz, CDCl3): d 2.33 (s, 3H,
MePh), 3.32 (s, 3H, MeNSO2), 3.54–3.55 (m, 1H, CHN),
3.93–3.98 ( m, 1H, CHN), 4.09–4.12 (m, 1H, CHPh), 4.53
(dd, J = 8.6, 11.6 Hz, 1H, CHSO2), 5.45 (d, J = 8.6 Hz, 1H,
CHAr), 6.67–7.43 (m, 13H, Ar); 13C NMR (125 MHz,
CDCl3): d 21.6, 30.8, 45.7, 56.4, 61.6, 68.9, 112.6, 118.3,
119.0, 128.1, 128.3, 128.5, 129.4, 129.9, 130.3, 136.8,
137.5, 147.5; ms: m/z (%) 404 (4) [M+], 149 (41), 81 (60),
69 (100), 57 (94).
2-Methoxy-5-methyl-7-phenyl-5,7,7a,8,9,10-hexahydrobenzo
[3,4][1,2]thiazino[6,5-b]pyrrolizin-11-ium-6-olate 6-oxide (5j).
White solid; yield: 60%; mp: 241–243ꢀC; IR (KBr), 1306 (ÀSO2);
1133 (ÀSO2) cmÀ1; (500 MHz, CDCl3) d 1.18–1.22 (m, 1H,
CHCH2CH2N), 1.36–1.40 (m, 1H, CHCH2CH2N), 1.74–1.77 (m,
1H, CH2CHCH2N), 1.86–1.90 (m, 1H, CH2CHCH2N), 1.94–1.98
(m, 1H, CH2CHCH2N), 2.84–2.87 (m, 1H, CHN), 3.41 (s, 3H,
MeN), 3.87 (s, 3H, OMe), 3.92–3.98 (m, 2H, CHN), 4.48–4.52 (m,
2H, CHSO2, ArCHN), 6.88–7.37 (m, 8H, Ar); 13C NMR (125 MHz,
CDCl3): d 26.2, 29.9, 32.7, 49.4, 56.0, 56.8, 62.6, 67.8, 69.1, 114.2,
114.8, 120.4, 127.4, 128.0, 129.0, 132.5, 132.9, 137.7, 157.5;
ms: m/z (%) 384 (2) [M+]), 320 (40), 250 (86), 174 (100), 57 (94).
5-Ethyl-1-methyl-3-phenyl-1,2,3,3a,5,9b-hexahydrobenzo[c]
pyrrolo[2,3-e][1,2] thiazine-4,4-dioxide (5f). White solid; yield:
61%; mp: 134–136ꢀC; IR (KBr) 1314 (ÀSO2), 1128 (ÀSO2)
cmÀ1 1H NMR (500 MHz, CDCl3): d 1.41 (t, 3H, J=7.1Hz,
;
MeCN), 2.26 (s, 3H, MeN), 2.54–2.58 (m, 1H, CHN),
3.53–3.56 (m, 1H, CHN), 3.66 (d, 1H, J = 9.0 Hz, ArCHN),
3.90–3.93 ( m, 1H, CHPh), 4.02–4.18 (m, 3H, CH2NSO2,
CHSO2), 7.23–7.44 (m, 9H, Ar); 13C NMR (125 MHz,
CDCl3): d 15.8, 39.7, 44.3, 47.4, 63.8, 70.6, 72.4, 123.4,
125.7, 127.7, 128.3, 129.2, 129.3, 130, 131.4, 140.5,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet