8
0
S. Göksu et al. / Bioorganic Chemistry 56 (2014) 75–82
À1
13C-NMR (100 MHz, Acetone-d6): 157.5 (C), 129.1 (CH), 128.8
(
OCH
3
), 47.6 (CH
034, 2934, 1689, 1608, 1445, 1403, 1344, 1151, 1121, 1084,
071. Anal. Calcd for (C16 S): C, 54.85; H, 5.18; N, 7.99; S,
2
N). IR (CH
2
Cl
2
, cm ): 3419, 3332, 3273, 3197,
3
1
9
(CH), 126.3 (C), 120.5 (CH), 110.5 (CH), 55.1 (OCH
3
), 42.6 (CH
2
N).
À1
H
18
N
2
O
5
IR (CH
2
Cl
2
, cm ): 3512, 3355, 3283, 2942, 2839, 1603, 1495,
.15; Found C, 54.81; H, 5.20; N, 7.97; S, 9.17.
1464, 1440, 1330, 1291, 1247, 1158, 1120, 1050, 1027. Anal. Calcd
for (C S): C, 44.43; H, 5.59; N, 12.95; S, 14.83; Found C,
8
12 2 3
H N O
4.1.5. Benzyl N-(2,4-dimethoxybenzyl)sulfamoylcarbamate (14)
44.45; H, 5.61; N, 12.98; S, 14.80.
General procedure described at 4.1.1 was applied to amine 8 to
1
give 14. White solid, yield 78%. Mp: 96–98 °C. H-NMR (400 MHz,
4.1.10. N-(3-methoxybenzyl)sulfamide (18)
DMSO-d
.32 (m, 5H, Ph–H), 7.15 (d, 1H, Ar–H, J = 8.4 Hz), 6.50 (d, 1H, Ar–
H, J = 2.3 Hz), 6.35 (dd, 1H, Ar–H, J = 2.3 and 8.4 Hz), 5.04 (s, 2H,
OCH ), 4.01 (d, 2H, CH N, J = 6.2 Hz), 3.73 (s, 3H, OCH ), 3.70 (s,
). C-NMR (100 MHz, DMSO-d ): 160.6 (C), 158.2 (CO),
52.2 (C), 136.5 (C of Ph), 129.8 (CH), 129.1 (2CH of Ph), 128.9
6
) d 11.21 (bs, 1H, NH), 7.87 (t, 1H, NH, J = 6.2 Hz), 7.37–
General Procedure described at 4.1.8 was applied to sulfamoylc-
7
arbamate 12 to give 18. White solid, yield 72%. Mp: 47–49 °C (lit.
1
[33] Mp: 45–46 °C) H-NMR (400 MHz, DMSO-d
6
) d 7.20 (t, 1H,
2
2
3
Ar–H, J = 8.1 Hz), 7.01 (t, 1H, NH, J = 6.6 Hz), 6.91–6.88 (m, 2H,
Ar–H), 6.78 (dd, 1H, Ar–H, J = 8.1 and 2.2 Hz), 6.60 (bs, 2H, NH ),
C-NMR
): 158.9 (C), 141.0 (C), 129.9 (CH), 120.5
1
3
3
1
H, OCH
3
6
2
13
2 3
4.02 (d, 2H, CH N, J = 6.6 Hz), 3.72 (s, 3H, OCH ).
(
CH of Ph), 128.7 (2CH of Ph), 118.0 (C), 104.9 (CH), 98.7 (CH),
(100 MHz, DMSO-d
6
6
7.3 (OCH
2
), 56.1 (OCH
3
), 55.9 (OCH
3
), 41.6 (CH
2
N). IR (CH
2
Cl
2
,
(CH), 113.8 (CH), 113.1 (CH), 55.7 (OCH
cm ): 3274, 2941, 2838, 1602, 1587, 1491, 1456, 1437, 1326,
3
), 46.7 (CH
2
N). IR (CH
2
Cl
2
,
À1
À1
cm ): 3478, 3287, 3019, 2935, 2851, 2350, 1735, 1614, 1590,
1
549, 1508, 1453, 1347, 1290, 1265, 1210, 1158, 1132, 1036. Anal.
Calcd for (C17 S): C, 53.67; H, 5.30; N, 7.36; S, 8.43; Found C,
3.70; H, 5.32; N, 7.35; S, 8.40.
1264, 1156, 1045. Anal. Calcd for (C
N, 12.95; S, 14.83; Found C, 44.40; H, 5.57; N, 12.93; S, 14.85.
8 12 2 3
H N O S): C, 44.43; H, 5.59;
20 2 6
H N O
5
4.1.11. N-(4-methoxybenzyl)sulfamide (19)
4.1.6. Benzyl N-(3,5-dimethoxybenzyl)sulfamoylcarbamate (15)
General Procedure described at 4.1.8 was applied to sulfamoylc-
General procedure described at 4.1.1 was applied to amine 9 to
give 15. White solid, yield 81%. Mp: 125–127 °C. H-NMR
arbamate 13 to give 19. White solid, yield 73%. Mp: 112–114 °C.
1
1
6
H-NMR (400 MHz, DMSO-d ) d 7.23 (d, 2H, Ar–H, J = 8.8 Hz),
(
400 MHz, Acetone-d6) d 9.93 (bs, 1H, NH), 7.43–7.32 (m, 5H,
6.91 (t, 1H, NH, J = 6.2 Hz), 6.86 (d, 2H, Ar–H, J = 8.8 Hz), 6.56 (bs,
13
Ph–H), 7.17 (t, 1H, NH, J = 6.3 Hz), 6.58 (d, 2H, Ar–H, J = 2.3 Hz),
6
CH
1H, NH
NMR (100 MHz, DMSO-d
114.2 (2CH), 55.7 (OCH
2 2 3
), 3.97 (d, 2H, CH N, J = 6.2 Hz), 3.71 (s, 3H, OCH ). C-
.39 (t, 1H, Ar–H, J = 2.3 Hz), 5.08 (s, 2H, OCH
2
), 4.23 (d, 2H,
6
): 159.0 (C), 131.2 (C), 129.7 (2CH),
13
À1
2
N, J = 6.3 Hz), 3.76 (s, 6H, 2OCH
3
). C-NMR (100 MHz, Ace-
3
), 46.3 (CH
2
2
N). IR (CH Cl
2
, cm ): 3327,
tone-d6): 161.2 (2C), 151.7 (CO), 139.8 (C), 136.1 (C of Ph), 128.7
2CH of Ph), 128.4 (CH of Ph), 128.3 (2CH of Ph), 106.0 (2CH),
3272, 3114, 1513, 1432, 1403, 1334, 1253, 1151, 1030. Anal. Calcd
for (C S): C, 44.43; H, 5.59; N, 12.95; S, 14.83; Found C,
(
8 12 2 3
H N O
9
9.5 (CH), 67.4 (OCH
2
), 54.9 (2OCH
3
), 47.5 (CH
2
N). IR (CH
2
Cl
2
,
44.46; H, 5.60; N, 12.93; S, 14.81.
À1
cm ): 3277, 3002, 2940, 2841, 1725, 1598, 1458, 1432, 1355,
1
297, 1225, 1205, 1157, 1064. Anal. Calcd for (C17
20
H N
2
O
6
S): C,
4.1.12. N-(2,4-dimethoxybenzyl)sulfamide (20)
5
3.67; H, 5.30; N, 7.36; S, 8.43; Found C, 53.69; H, 5.34; N, 7.33;
General Procedure described at 4.1.8 was applied to sulfamoylc-
arbamate 14 to give 20. White solid, yield 77%. Mp: 88–90 °C. H-
1
S, 8.41.
NMR (400 MHz, DMSO-d
1H, NH, J = 6.5 Hz), 6.53 (bs, 1H, NH
J = 2.3 Hz), 6.47 (dd, 1H, Ar–H, J = 8.4 and 2.3 Hz), 3.96 (d, 2H,
6
) d 7.22 (d, 1H, Ar–H, J = 8.4 Hz), 6.62 (t,
4
.1.7. Benzyl N-(3,4,5-trimethoxybenzyl)sulfamoylcarbamate (16)
2
), 6.50 (d, 1H, Ar–H,
General procedure described at 4.1.1 was applied to amine 10 to
1
13
give 16. White solid, yield 83%. Mp: 131–133 °C. H-NMR
2 3 3
CH N, J = 6.5 Hz), 3.75 (s, 3H, OCH ), 3.72 (s, 3H, OCH ). C-NMR
(
6
4
OCH
(
(
5
1
1
6
400 MHz, CDCl
3
) d 7.54 (bs, 1H, NH), 7.36–7.30 (m, 5H, Ph–H),
.52 (s, 2H, Ar–H), 5.57 (t, 1H, NH, J = 6.3 Hz), 5.11 (s, 2H, OCH ),
.17 (d, 2H, CH N, J = 6.3 Hz), 3.83 (s, 6H, 2OCH ), 3.82 (s, 3H,
). C-NMR (100 MHz, CDCl ): 153.7 (2C), 151.4 (CO), 134.6
(100 MHz, DMSO-d
6
): 160.3 (C), 158.1 (C), 129.7 (CH), 119.0 (C),
2
104.9 (CH), 98.7 (CH), 56.0 (OCH
3
), 55.9 (OCH
3
), 41.3 (CH
2
N). IR
À1
2
3
2
(CH Cl
2
, cm ): 3273, 3109, 3002, 2939, 2834, 1614, 1590, 1508,
13
3
3
1459, 1420, 1328, 1290, 1208, 1157, 1131, 1034. Anal. Calcd for
(C S): C, 43.89; H, 5.73; N, 11.37; S, 13.02; Found C,
C), 131.2 (C of Ph), 129.1 (CH of Ph), 129.0 (2CH of Ph), 128.8
C), 128.7 (2CH of Ph), 105.1 (2CH), 68.9 (OCH
9 14 2 4
H N O
2
), 61.1 (OCH
, cm ): 3257, 2939, 2834,
3
),
43.91; H, 5.75; N, 11.36; S, 13.00.
À1
6.4 (2OCH
3
), 48.4 (CH
2 2
N). IR (CH Cl
2
737, 1594, 1546, 1508, 1463, 1420, 1346, 1328, 1235, 1156,
127, 1003. Anal. Calcd for (C18 S): C, 52.67; H, 5.40; N,
.83; S, 7.81; Found C, 52.64; H, 5.42; N, 6.84; S, 7.83.
4.1.13. N-(3,5-dimethoxybenzyl)sulfamide (21)
H
22
N
2
O
7
General Procedure described at 4.1.8 was applied to sulfamoylc-
arbamate 15 to give 21. White solid, yield 75%. Mp: 108–110 °C.
1
H-NMR (400 MHz, DMSO-d
6
) d 6.99 (t, 1H, NH, J = 6.6 Hz), 6.59
4
.1.8. General procedure for the synthesis of sulfamides
(bs, 1H, NH
J = 2.2 Hz), 3.98 (d, 2H, CH
NMR (100 MHz, DMSO-d
99.4 (CH), 55.8 (2OCH
3327, 3266, 3002, 2935, 2834, 1737, 1598, 1464, 1429, 1404,
1356, 1317, 1206, 1130, 1049. Anal. Calcd for (C S): C,
2
), 6.50 (d, 2H, Ar–H, J = 2.2 Hz), 6.34 (t, 1H, Ar–H,
13
(
Hydrogenolysis of sulfamylcarbamates)
2 3
N, J = 6.6 Hz), 3.70 (s, 6H, 2OCH ). C-
Sulfamoylcarbamate (2.63 mmol) in MeOH (50 mL) and Pd–C
6
): 161.0 (2C), 141.7 (C), 106.2 (2CH),
À1
(
50 mg) were placed into a 100-mL flask. A balloon filled with H
provided deoxy-
2
3
2 2
), 46.8 (CH N)). IR (CH Cl
2
, cm ): 3350,
gas (3 L) was fitted to the flask. Flushing with H
2
genation. The mixture was hydrogenated at rt for 4 h. Removal of
the catalyst by filtration and crystallization of the residue with
EtOAc-hexane furnished sulfamides.
9 14 2 4
H N O
43.89; H, 5.73; N, 11.37; S, 13.02; Found C, 43.90; H, 5.74; N,
11.35; S, 13.01.
4.1.9. N-(2-methoxybenzyl)sulfamide (17)
4.1.14. N-(3,4,5-trimethoxybenzyl)sulfamide (22)
General Procedure described at 4.1.8 was applied to sulfamoylc-
arbamate 11 to give 17. White solid, yield 76%. Mp: 59–61 °C. H-
NMR (400 MHz, Acetone-d6) d 7.40–7.37 (m, 1H, Ar–H), 7.26 (td,
General Procedure described at 4.1.8 was applied to sulfamoylc-
arbamate 16 to give 22. White solid, yield 68%. Mp: 149–151 °C. H-
1
1
NMR (400 MHz, DMSO-d
Ar–H), 6.63 (bs, 2H, NH ), 4.01 (d, 2H, CH
2OCH ), 3.63 (s, 3H, OCH
(2C), 136.9 (C), 134.8 (C), 105.5 (2CH), 60.7 (OCH
6
) d 6.99 (t, 1H, NH, J = 6.5 Hz), 6.66 (s, 2H,
N, J = 6.5 Hz), 3.77 (s, 6H,
). C-NMR (100 MHz, DMSO-d ): 153.3
), 56.4 (2OCH ),
1
(
H, Ar–H, J = 8.1 and 1.7 Hz), 6.96 (d, 1H, Ar–H, J = 8.1 Hz), 6.91
td, 1H, Ar–H, J = 7.5 and 1.1 Hz), 5.91 (bs, 2H, NH ), 5.85 (t, 1H,
N, J = 6.2 Hz), 3.84 (s, 3H, OCH ).
2
2
1
3
2
3
3
6
NH
,
J = 6.2 Hz), 4.25 (d, 2H, CH
2
3
3
3