Arch. Pharm. Chem. Life Sci. 2014, 347, 68–76
New Sulphamides and Sulphonamides as CA and AChE Inhibitors
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(0.80 g, 3.86 mmol) in CH2Cl2 (30 mL) and NEt3 (0.55 g, 5.40 mmol)
was added to the solution of CSI dropwise and stirred at 0°C for
1 h, then at room temperature for 3 h. The reaction mixture was
cooled to 0°C and to this mixture a solution of 0.1 N HCl (50 mL)
was added. Organic phase was separated and H2O phase was
extracted with CH2Cl2 (2 ꢂ 30 mL). Combined organic layers were
dried over Na2SO4 and the solvent was evaporated. Column
chromatography of the residue on silica gel (30 g) with 30%
EtOAc–hexane yielded carbamate 8 (0.98 g, 60%) as white solid.
The same experimental procedure was also used for the synthesis
of compounds 9 (%54) and 10 (50%).
1256, 1219, 1159, 1119, 1089, 1068, 1028. Anal. calcd. for
(C21H26N2O6S): C, 58.05; H, 6.03; N, 6.45; S, 7.38. Found: C, 58.10;
H, 5.99; N, 6.48; S, 7.32.
Standard procedure for the synthesis of sulphamides
(hydrogenolysis of sulphamoylcarbamates): N-(6,7-
Dimethoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-
sulphamide (11)
Into a 100-mL flask Pd-C (50 mg) and sulphamoylcarbamate 8
(0.7 g, 1.66 mmol) in MeOH (50 mL) were added. A balloon filled
with H2 gas (3 L) was fitted to the flask. The mixture was
deoxygenated by flushing with H2 and then hydrogenated at
room temperature for 4 h. The catalyst was removed by filtration.
Recrystallization of the residue from EtOAc–hexane gave 11
(0.35 g, 73% yield).
Benzyl N-(6,7-dimethoxy-1,2,3,4-tetrahydronaphthalen-
1-yl)sulphamoylcarbamate (8)
White solid. Mp 88–90°C. 1H NMR (400 MHz, CDCl3):
d (ppm) ¼ 7.36–7.31 (m, 6H, 5Ph-H and NH), 6.85 (s, 1H, Ar–H),
6.52 (s, 1H, Ar–H), 5.37 (d, 1H, NH, J ¼ 7.6 Hz), 5.20 (d, A part of AB;
1H, Ha of OCH2, J ¼ 12.1 Hz), 5.14 (d, B part of AB; 1H, Hb of OCH2,
J ¼ 12.1 Hz), 4.53–4.51 (m, 1H, CH–N), 3.83 (s, 3H, OCH3), 3.78
(s, 3H, OCH3), 2.68–2.60 (m, 2H, CH2), 1.91–1.87 (m, 2H, CH2),
1.78–1.72 (m, 2H, CH2). 13C NMR (100 MHz, CDCl3): d (ppm) ¼
151.6 (CO), 149.1 (C), 147.9 (C), 134.8 (C of Ph), 130.1 (C), 129.1 (CH
of Ph), 129.0 (2CH of Ph), 128.6 (2CH of Ph), 126.5 (C), 111.7 (2CH),
68.7 (OCH2), 56.12 (OCH3), 56.06 (OCH3), 53.2 (CH–N), 30.0 (CH2),
28.7 (CH2), 19.4 (CH2). IR (CH2Cl2, cmꢀ1): 3417, 3332, 3272, 3193,
3056, 2928, 2855, 1688,1608, 1445, 1402, 1343, 1265, 1163, 1120,
1084, 1071. Anal. calcd. for (C20H24N2O6S): C, 57.13; H, 5.75; N,
6.66; S, 7.63. Found: C, 57.08; H, 5.82; N, 6.58; S, 7.65.
Sulphamides 12–13 were also synthesized by this procedure
with yields of 76 and 80%, respectively.
N-(6,7-Dimethoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-
sulphamide (11)
White solid. Mp: 152–155°C. 1H NMR (400 MHz, CDCl3): d
(ppm) ¼ 6.95 (s, 1H, Ar–H), 6.52 (s, 1H, Ar–H), 4.78 (bs, 2H,
NH2), 4.62–4.54 (m, 2H, NH and CH–N), 3.84 (s, 3H, OCH3), 3.83
(s, 3H, OCH3), 2.69–2.63 (m, 2H, CH2), 2.03–1.98 (m, 2H, CH2), 1.82–
1.78 (m, 2H, CH2). 13C NMR (100 MHz, CDCl3): d (ppm) ¼ 148.8 (C),
147.8 (C), 130.1 (C), 127.5 (C), 111.8 (CH), 111.5 (CH), 56.3 (OCH3),
56.1 (OCH3), 52.3 (CH–N), 30.7 (CH2), 28.8 (CH2), 19.4 (CH2). IR
(CH2Cl2, cmꢀ1): 3495, 3417, 3325, 2969, 2952, 2926, 2845, 1706,
1647, 1609, 1512, 1453, 1420, 1353, 1317, 1286, 1255, 1216, 1155,
1116, 1088, 1074, 1051, 1037, 1017. Anal. calcd. for (C12H18N2O4S):
C, 50.33; H, 6.34; N, 9.78; S, 11.20. Found: C, 50.38; H, 6.40; N, 9.72;
S, 11.18.
Benzyl N-(6,7-dimethoxy-1,2,3,4-tetrahydronaphthalen-
2-yl)sulphamoylcarbamate (9)
White solid. Mp: 140–142°C. 1H NMR (400 MHz, CDCl3):
d (ppm) ¼ 7.49 (bs, 1H, NH), 7.41–7.34 (m, 5H, Ph-H), 6.54 (s,
1H, Ar–H), 6.45 (s, 1H, Ar–H), 5.23 (d, 1H, NH, J ¼ 6.9 Hz), 5.20 (s,
2H, OCH2), 3.87 (s, 3H, OCH3), 3.86 (s, 3H, OCH3), 3.77–3.69 (m, 1H,
CH–N), 2.97 (dd, A part of AB; 1H, Ha of CH2, J ¼ 5.0 and 16.0 Hz),
2.78–2.74 (m, 2H, CH2), 2.63 (dd, B part of AB; 1H, Hb of CH2, J ¼ 8.0
and 16.0 Hz), 2.04–1.96 (m, 1H, H of CH2), 1.81–1.72 (m, 1H, H of
CH2). 13C NMR (100 MHz, CDCl3): d (ppm) ¼ 151.2 (CO), 147.8 (C),
147.5 (C), 134.7 (C of Ph), 128.9 (CH of Ph), 128.8 (2CH of Ph), 128.5
(2CH of Ph), 126.8 (C), 124.7 (C), 112.0 (CH), 111.5 (CH), 68.6 (OCH2),
56.0 (OCH3), 55.9 (OCH3), 50.7 (CH-N), 35.5 (CH2), 29.1 (CH2), 26.4
(CH2). IR (CH2Cl2, cmꢀ1): 3257, 3064, 3030, 3002, 2935, 2840, 1727,
1610, 1517, 1452, 1352, 1295, 1241, 1226, 1159, 1114, 1071, 1017.
Anal. calcd. for (C20H24N2O6S): C, 57.13; H, 5.75; N, 6.66; S, 7.63.
Found: C, 57.11; H, 5.78; N, 6.64; S, 7.60.
N-(6,7-Dimethoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-
sulphamide (12)
White solid. Mp: 158–160°C. 1H NMR (400 MHz, CDCl3):
d (ppm) ¼ 6.56 (s, 1H, Ar–H), 6.54 (s, 1H, Ar–H), 4.76 (bs, 3H, NH
and NH2), 3.81–3.76 (m, 7H, 2OCH3 and CH–N), 3.09 (dd, A part of
AB; 1H, Ha of CH2, J ¼ 4.6 and 15.7 Hz), 2.82 (t, 2H, CH2, J ¼ 6.3 Hz),
2.71 (dd, B part of AB; 1H, Hb of CH2, J ¼ 8.0 and 15.7 Hz), 2.11–
2.04 (m, 1H, H of CH2), 1.87–1.78 (m, 1H, H of CH2). 13C NMR
(100 MHz, CDCl3): d (ppm) ¼ 147.6 (C), 147.4 (C), 126.9 (C), 125.2
(C), 111.9 (CH), 111.4 (CH), 55.9 (OCH3), 55.88 (OCH3), 50.1 (CH–N),
36.0 (CH2), 29.4 (CH2), 26.5 (CH2). IR (CH2Cl2, cmꢀ1): 3501, 3338,
3252, 3098, 2927, 2851, 1735, 1610, 1547, 1517, 1460, 1449, 1345,
1328, 1265, 1247, 1222, 1208, 1158, 1112, 1071, 1015. Anal. calcd.
for (C12H18N2O4S): C, 50.33; H, 6.34; N, 9.78; S, 11.20. Found: C,
50.27; H, 6.29; N, 9.83; S, 11.26.
Benzyl-N-((6,7-dimethoxy-1,2,3,4-tetrahydronaphthalen-
1-yl)methyl)sulphamoylcarbamate (10)
White solid. Mp: 62–64°C. 1H NMR (400 MHz, CDCl3):
d (ppm) ¼ 7.51 (bs, 1H, NH), 7.36–7.31 (m, 5H, Ph–H), 6.62
(s, 1H, Ar–H), 6.55 (s, 1H, Ar–H), 5.25 (t, 1H, NH, J ¼ 6.3 Hz), 5.16 (s,
2H, OCH2), 3.83 (s, 6H, 2OCH3), 3.28–3.23 (m, 2H, CH and 1H of
CH2NH), 2.96–2.93 (m, 1H, CH2NH), 2.67–2.64 (m, 2H, CH2), 1.83–
1.73 (m, 4H, 2CH2). 13C NMR (100 MHz, CDCl3): d (ppm) ¼ 151.5
(CO), 148.0 (C), 147.5 (C), 134.7 (C of Ph), 130.2 (C), 129.1 (CH of Ph),
129.0 (2CH of Ph), 128.6 (2CH of Ph), 127.8 (C), 112.3 (CH), 111.5
(CH), 68.8 (OCH2), 56.3 (OCH3), 56.0 (OCH3), 48.9 (CH2–N), 37.2
(CH), 29.3 (CH2), 25.9 (CH2), 19.7 (CH2). IR (CH2Cl2, cmꢀ1): 3270,
3064, 3034, 2932, 2856, 2094, 1735, 1610, 1514, 1464, 1454, 1353,
N-((6,7-Dimethoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-
methyl)sulphamide (13)
White solid. Mp: 105–107°C. 1H NMR (400 MHz, CDCl3):
d (ppm) ¼ 6.71 (s, 1H, Ar–H), 6.55 (s, 1H, Ar–H), 4.89 (bs, 2H,
NH2), 4.80 (t, 1H, NH, J ¼ 6.4 Hz), 3.84 (s, 3H, OCH3), 3.82 (s, 3H,
OCH3), 3.34–3.25 (m, 2H, CH and 1H of CH2–N), 2.96–2.94 (m, 1H,
1H of CH2–N), 2.67–2.65 (m, 2H, CH2), 1.83–1.73 (m, 4H, 2CH2).
13C NMR (100 MHz, CDCl3): d (ppm) ¼ 147.5 (C), 147.1 (C), 130.1 (C),
128.3 (C), 111.9 (CH), 111.6 (CH), 56.2 (OCH3), 55.8 (OCH3), 48.4
(CH2–N), 37.1 (CH), 29.1 (CH2), 25.7 (CH2), 19.6 (CH2). IR (CH2Cl2,
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