M. I. El-Gamal et al. / Bioorg. Med. Chem. xxx (2016) xxx–xxx
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4.3.1. 4-(Cyclohexanecarboxamido)phenyl methanesulfonate
(1a)
Yield: 87%; mp: 173–6 °C; IR (KBr disc, cmÀ1): 3324 (NH), 2931,
4.3.6. 4-(Cyclohexanecarboxamido)phenyl 4-(tert-butyl)
benzenesulfonate (1f)
Yield: 85%; mp: 174–7 °C; IR (KBr disc, cmÀ1): 3369 (NH), 2956,
2922, 2851 (CAH stretching), 1671 (C@O), 1406, 1378 (OSO2); 1H
NMR (400 MHz, CDCl3) d 7.74 (d, 2H, Ar-H, J = 8.0 Hz), 7.52 (d,
2H, NH, J = 4.0 Hz), 7.46 (d, 2H, Ar-H, J = 8.0 Hz), 7.34 (br s, 1H,
NH), 6.92 (d, 2H, Ar-H, J = 8.0 Hz) 2.25–2.17 (m, 1H, cyclohexyl-
H), 1.92 (d, 2H, J = 12.0 Hz), 1.84–1.80 (m, 2H, cyclohexyl-H),
1.70–1.66 (m, 2H, cyclohexyl-H), 1.55–1.46 (m, 2H, cyclohexyl-
H), 1.34 (s, 9H, tert-butyl-9H), 1.27–1.24 (m, 2H, cyclohexyl-H);
13C NMR (100 MHz, CDCl3) d 174.5 (C@O), 145.4, 137.1, 132.2,
128.4 (2C), 126.2 (2C), 122.9 (2C), 120.5 (2C) [Ar-C], 46.5, 29.6
(2C), 25.6 (3C) [aliph. C]. LC–MS: m/z 416.21 [M+ +1].
2853 (CAH stretching), 1668 (C@O), 1524, 1371 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.58 (d, 2H, Ar-H, J = 8.0 Hz), 7.43 (s, 1H, NH),
7.21 (d, 2H, Ar-H, J = 8.0), 3.12 (s, 3H, CH3), 2.28–2.20 (m, 1H, cyclo-
hexyl-H), 1.94 (d, 2H, cyclohexyl-H, J = 12.0 Hz), 1.86–1.82 (m, 2H,
cyclohexyl-H), 1.72–1.67 (m, 2H, cyclohexyl-H), 1.58–1.49 (m, 2H,
cyclohexyl-H), 1.29–1.26 (m, 2H, cyclohexyl-H); 13C NMR
(100 MHz, CDCl3) d 174.6 (C@O), 145.0, 137.4, 122.5 (2C), 121.1
(2C) [Ar-C], 46.4, 37.2, 29.6 (2C), 25.6 (2C) [aliph. C]; LC–MS: m/z
298.07 [M+ +1].
4.3.2. 4-(Cyclohexanecarboxamido)phenyl ethanesulfonate (1b)
Yield: 85%; mp: 140–2 °C; IR (KBr disc, cmÀ1): 3309 (NH), 2924,
2853 (CAH stretching), 1660 (C@O), 1527, 1349 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.59 (br s, 1H, NH), 7.57 (d, 2H, Ar-H,
J = 8.0 Hz), 7.19 (d, 2H, Ar-H, J = 12.0 Hz), 3.26 (q, 2H, CH2CH3,
J = 8.0 Hz), 2.28–2.20 (m, 1H, aliph.-H), 1.94–1.91 (m, 3H, cyclo-
hexyl-H), 1.85–1.81 (m, 2H, cyclohexyl-H), 1.71–1.68 (m, 1H,
cyclohexyl-H), 1.52 (t, 3H, CH2CH3, J = 8.0 Hz), 1.28–1.26 (m, 3H);
13C NMR (100 MHz, CDCl3) d 174.7 (C@O), 144.8, 137.3, 122.5
(2C), 121.1 (2C) [Ar-C], 46.4, 44,9, 29.6 (2C), 25.6 (2C), 8.2 [aliph.
C]; LC–MS: m/z 312.24 [M+ +1].
4.3.7. 4-(Cyclohexanecarboxamido)phenyl 4-fluorobenzene-
sulfonate (1g)
Yield: 87%; mp: 154–5 °C; IR (KBr disc, cmÀ1): 3316 (NH), 2929,
2853 (CAH stretching), 1665 (C@O), 1519, 1379 (OSO2); 1H NMR
(400 MHz, CDCl3)
d 7.85–7.81(m, 2H, Ar-H), (d, 2H, Ar-H,
J = 8.0 Hz), 7.47 (d, 2H, Ar-H, J = 8.0 Hz), 7.27 (br s, 1H, NH), 7.22–
7.17 (m, 2H), 6.91 (d, 2H, Ar-H, J = 8.0 Hz), 2.44 (s, 3H, CH3),
2.25–2.17 (m, 1H, cyclohexyl-H), 1.93 (d, 2H, cyclohexyl-H,
J = 12.0 Hz), 1.85–1.81 (m, 2H, cyclohexyl-H), 1.71–1.69 (m, 1H,
cyclohexyl-H), 1.57–1.47 (m, 2H, cyclohexyl-H), 1.35–1.21 (m,
3H, cyclohexyl-H); 13C NMR (100 MHz, CDCl3) d 174.5 (C@O),
145.2, 137.2, 131.5 (2C), 131.4, 122.9 (2C), 120.6, 116.7 (2C),
116.5 (2C) [Ar-C], 46.5, 29.6 (2C), 25.6 (3C) [aliph. C]; LC–MS: m/
z 378.23 [M+ +1].
4.3.3. 4-(Cyclohexanecarboxamido)phenyl propane-1-sulfonate
(1c)
Yield: 86%; mp: 150–3 °C; IR (KBr disc, cmÀ1): 3313 (NH), 2924,
2853 (CAH stretching), 1661 (C@O), 1528, 1335 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.59 (br s, 1H, NH), 7.56 (d, 2H, Ar-H,
J = 8.0 Hz), 7.18 (d, 2H, Ar-H, J = 8.0 Hz), 3.22–3.18 (m, 2H, aliph.-
H), 2.28–2.20 (m, 1H), 2.03–2.00 (m, 1H, aliph.-H), 1.98 (d, 1H,
aliph.-H, J = 8.0 Hz), 1.92 (d, 2H, cyclohexyl-H, J = 16.0 Hz), 1.84–
1.77 (m, 2H, cyclohexyl-H), 1.71–1.69 (m, 1H, cyclohexyl-H), 1.58–
1.48 (m, 2H, cyclohexyl-H), 1.27–1.25 (m, 4H, cyclohexyl-H), 1.11
(t, 3H, CH2CH2CH3, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) d 174.8
(C@O), 144.8, 137.2, 122.5 (2C), 121.1 (2C) [Ar-C], 51.9, 46.3, 29.6
(2C), 25.6 (2C), 17.3, 12.8 [aliph. C]; LC–MS: m/z 326.0 [M+ +1].
4.3.8. 4-(Cyclohexanecarboxamido)phenyl 4-(trifluoromethyl)
benzenesulfonate (1h)
Yield: 85%; mp: 171–2 °C; IR (KBr disc, cmÀ1): 3327 (NH), 2931,
2850 (CAH stretching), 1661 (C@O), 1407, 1386 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.96 (d, 2H, Ar-H, J = 8.0 Hz), 7.80 (d, 2H, Ar-
H, J = 8.0 Hz), 7.49 (d, 2H, Ar-H, J = 8.0 Hz), 7.36 (br s, 1H, NH),
6.92 (d, 2H, Ar-H, J = 8.0 Hz), 2.25–2.18 (m, 1H, cyclohexyl-H),
1.92 (d, 2H, cyclohexyl-H, J = 12.0 Hz), 1.85–1.81 (m, 2H, cyclo-
hexyl-H), 1.71–1.68 (m, 2H, cyclohexyl-H), 1.56–1.47 (m, 2H,
cyclohexyl-H), 1.31–1.24 (m, 2H, cyclohexyl-H); 13C NMR
(100 MHz, CDCl3) d 174.6 (C@O), 145.0, 138.8, 137.5, 136.0, 129.1
(2C), 126.4 (2C), 126.3, 122.7 (2C), 120.7 (2C) [Ar-C], 46.5, 29.6
(2C), 25.6 (3C) [aliph. C]; LC–MS: m/z 427.94 [M+ +1].
4.3.4. 4-(Cyclohexanecarboxamido)phenyl benzenesulfonate
(1d)
Yield: 80%; mp: 156–9 °C; IR (KBr disc, cmÀ1): 3319 (NH), 2927,
2854 (CAH stretching), 1665 (C@O), 1519, 1377 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.81–7.79 (m, 2H, Ar-H), 7.68–7.64 (m, 2H,
Ar-H), 7.53–7.46 (m, 4H, Ar-H), 6.87 (d, 2H, NH, J = 8.0), 2.26–
2.18 (m, 1H, cyclohexyl-H), 1.89 (d, 2H, cyclohexyl-H,
J = 12.0 Hz), 1.80–1.77 (m, 2H, cyclohexyl-H), 1.67 (d, 1H, cyclo-
hexyl-H, J = 8.0 Hz), 1.50 (d, 2H, cyclohexyl-H, J = 12.0 Hz), 1.26–
1.21 (m, 3H, cyclohexyl-H); 13C NMR (100 MHz, CDCl3) d 174.8
(C@O), 145.2, 137.4, 135.1, 134.3, 129.2 (2C), 128.5 (2C), 122.7
(2C), 120.7 (2C) [Ar-C], 46.4, 29.7 (2C), 29.6, 25.6 (2C), 25.5 [aliph.
C]; LC–MS: m/z 360.2 [M+ +1].
4.3.9. 4-(Cyclopentanecarboxamido)phenyl 4-methylbenzene-
sulfonate (1i)
Yield: 80%; mp: 151–3 °C; IR (KBr disc, cmÀ1): 3731 (NH), 2917,
2845 (CAH stretching), 1655 (C@O), 1527, 1375 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.69 (d, 2H, Ar-H, J = 12.0 Hz), 7.62 (br s, 1H,
NH), 7.47 (d, 2H, Ar-H, J = 8.0 Hz), 7.31 (d, 2H, Ar-H, J = 8.0 Hz),
6.89 (d, 2H, Ar-H, J = 8.0 Hz), 2.71–2.63 (m, 1H, cyclopentyl-H),
2.45 (s, 3H, CH3), 1.92–1.74 (m, 6H, cyclopentyl-H), 1.61–1.57 (m,
2H, cyclopentyl-H); 13C NMR (100 MHz, CDCl3) d 175.0 (C@O),
145.5, 145.2, 137.3, 132.1, 129.8 (2C), 128.5 (2C), 122.8 (2C),
120.5 (2C) [Ar-C], 46.4, 30.5 (2C), 26.0 (2C), 21.7 [aliph. C]; LC–
MS: m/z 359.75 [M+ +1].
4.3.5. 4-(Cyclohexanecarboxamido)phenyl 4-methylbenzene-
sulfonate (1e)
Yield: 88%; mp: 171–4 °C; IR (KBr disc, cmÀ1): 3740 (NH), 2927,
2855 (CAH stretching), 1656 (C@O), 1528, 1377 (OSO2); 1H NMR
(400 MHz, CDCl3) d 7.68 (d, 2H, Ar-H, J = 8.0 Hz), 7.45 (d, 2H, Ar-
H, J = 8.0 Hz), 7.30 (d, 2H, Ar-H, J = 8.0 Hz), 7.25 (br s, 1H, NH),
6.90 (d, 2H, Ar-H, J = 8.0 Hz), 2.44 (s, 3H, CH3), 2.20–2.17 (m, 1H,
cyclohexyl-H), 1.92 (d, 2H, cyclohexyl-H, J = 12.0 Hz), 1.85–1.81
(m, 2H, cyclohexyl-H), 1.71–1.68 (m, 1H, cyclohexyl-H), 1.55–
1.46 (m, 2H, cyclohexyl-H), 1.32–1.30 (m, 2H, cyclohexyl-H); 13C
NMR (100 MHz, CDCl3) d 174.4 (C@O), 145.4, 137.0, 132.2, 129.8
(2C), 128.6 (2C), 122.9 (2C), 120.5 (2C) [Ar-C], 46.5, 29.6 (2C),
25.6 (2C), 21.7, 14.1 [aliph. C]; LC–MS: m/z 373.91 [M+ +1].
4.4. Synthesis of the target sulfamate compounds 1j–m
A solution of compound 4a,b (0.456 mmol) in dry DMF (10 mL)
was cooled to 0 °C, and NaH (60% dispersion in mineral oil,
18.2 mg, 0.456 mmol) was added thereto under nitrogen atmo-
sphere.
A solution of the appropriate sulfamoyl chloride
(2.0 mmol) in dry DMF (3 mL) was added dropwise to the reaction
mixture at the same temperature. The reaction mixture was stirred
at room temperature overnight. After reaction completion, the
mixture was quenched with ethyl acetate (10 mL) and water