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Z. Regaınia et al. / Tetrahedron 56 (2000) 381–387
385
[N-(N-BOC)-sulfamoyl]-prolinol 15. Yield85%; Rf0.36
(CH2Cl2–MeOH 95:5); Mp: 108–110ЊC; IR (KBr, n cmϪ1):
3500 (OH), 3250 (NH), 1708 (CyO), 1340 and 1154 (SO2).
1H NMR (CDCl3, d): 7.65 (s, 1H, exch, NHBOC), 4.11 (s
br., 1H, exch, OH), 3.86 (m, 1H, Cء
H), 3.64 (m, 2H,
CH2OH), 3.38 (m, 2H, CH2), 2.20 (m, 4H, 2×CH2), 1.48
(s, 9H, tBu). MS (NOBA, FABϾ0): 281, [MϩH]ϩ; 225.
Anal (C10H20N2O5S): calcd % C 42.86; H 7.14; N 10.00;
found % C 42.90; H 7.18; N 9.88.
(m, 1H, Cء
H), 1.74 (m, 1H, CH), 1.58 (m, 2H, CH2), 1.52 (s,
9H, tBu), 0.85 (2d, 6H, 2×CH3). MS (NOBA, FABϾ0):
315, 317; [MϩH]ϩ; 214 (C11H23ClN2O4S).
N1-BOC,N3-[(2-chloro-1-benzyl) ethyl] sulfamide 21.
Yield95%; Rf0.95 (CH2Cl2–MeOH 95:5); Mp: 115–
117ЊC; IR (KBr, n cmϪ1): 3250 (NH), 1702 (CyO), 1325
1
and 1143 (SO2). H NMR (CDCl3, d): 7.58 (s, 1H, exch,
NHBOC), 7.20 (m, 6H, ArHϩNH), 3.91 (m, 1H, Cء
H), 3.55
and 3.42 (2dd, 2H, J4.42, 7.04 Hz, CH2Cl), 3.21 and 2.82
(2dd, 2H, J5.0, 8.70 Hz, CH2Ph), 1.42 (s, 9H, tBu)
(C14H21ClN2O4S).
General procedure for the synthesis of N1-BOC,N3-
(2-chloroalkyl) sulfamides
N1(N-BOC-sulfamoyl)-2-(2-chloroethyl) pyrrolidine 22.
Yield86%; Rf0.88 (CH2Cl2–MeOH 95:5); Mp: 79–
80ЊC; [a]DϪ5.5 (c1, MeOH); IR (KBr, n cmϪ1): 3250
(NH), 1702 (CyO), 1325 and 1170 (SO2). 1H NMR (CDCl3,
d): 7.10 (s br,1H, exch, NHBOC), 4.38 (m, 1H, Cء
H) 3.70
and 3.50 (2dd, 2H, Jvic3.50 Hz and JgemϪ7.89 Hz,
CH2Cl), 3.48, 2.02, 1.89 (3m, 3×2H, 3 CH2 pyrr), 1.46 (s,
9H, tBu). MS (NOBA, FABϾ0): 299–301, [MϩH]ϩ; 263,
[MϩH]ϩϪHCl; 198 [MϩH]ϩϪBOC (C10H19ClN2O4S).
A solution of BOC-sulfamoylaminoalcohols (5.35 mmol),
triphenylphosphine (16.05 mmol) and CCl4 (16.05 mmol)
in 100 mL of anhydrous acetonitrile was refluxed for
8 h.16 After cooling to room temperature, the solution was
concentrated in vacuo. The residue was triturated with
diethyl ether (3×150 mL). Triphenyl phosphine oxide
which precipitates in the combined organic layers, was
removed by filtration. The filtrate was concentrated and
the residue purified on silica gel (CH2Cl2) to afford the
methylene chloride derivatives in 85–95% yield.
Cyclization with K2CO3 in DMSO: general procedure
N1-BOC,N3-(2-chloroethyl) sulfamide 16. Yield85%;
Rf0.76 (CH2Cl2–MeOH 95:5); Mp: 132ЊC; IR (KBr, n
cmϪ1): 3325 and 3250 (NH), 1705 (CyO), 1350, 1140
The 2-chloroalkyl compounds (10 mmol) were dissolved in
dimethylsulfoxide (DMSO) and K2CO3 (1.5 equiv., anhy-
drous), was added in one fraction. The resulting mixture
was stirred at room temperature for 8 h, diluted with
dichloromethane (200 mL) and acidified with 5% HCl.
The organic layer was washed with water, dried (Na2SO4)
and concentrated in vacuo. Recrystallization of the crude
product in CH2Cl2/petroleum ether (1:5) afforded pure
expected cyclosulfamides 23–25 and 34 and 35.
1
(SO2). H NMR (CDCl3, d): 7.35 (s, 1H, exch, NHBOC),
5.65 (t, 1H, exch, NH), 3.68 (t, 2H, J6.0 Hz, CH2Cl), 3.42
(q, 2H, J6.0 Hz, CH2NH), 1.52 (s, 9H, tBu). MS (NOBA,
FABϾ0): 259–261, [MϩH]ϩ, 158–160 [MϩH]ϩϪBOC
(C7H15ClN2O4S).
N1-BOC,N3-methyl,N3-(2-chloroethyl) sulfamide 17. Yield
85%; Rf0.76 (CH2Cl2–MeOH 95:5); Mp: 132ЊC; IR (KBr,
n cmϪ1): 3325 and 3250 (NH), 1705 (CyO), 1350, 1140
N2-BOC-1,2,5-thiadiazolidine 1,1-dioxide 23. Yield90%;
Rf0.67 (CH2Cl2–MeOH 95:5); Mp: 143ЊC; IR (KBr, n
cmϪ1): 3300 (NH), 1695 (CyO), 1360 and 1145 (SO2).
1H-NMR (CDCl3, d): 4.76 (t, 1H, exch, NH), 3.92 (t, 2H,
J6.42 Hz, CH2), 3.54 (q, 2H, J7.61 Hz, CH2NH), 1.52
(s, 9H, tBu). MS (NOBA, FABϾ0): 223, [MϩH]ϩ; 167;
122 (C7H14N2O4S).
1
(SO2). H NMR (CDCl3, d): 7.35 (s, 1H, exch, NHBOC),
5.65 (t, 1H, exch, NH), 3.68 (t, 2H, J6.0 Hz, CH2Cl), 3.42
(q, 2H, J6.0 Hz, CH2NH), 1.52 (s, 9H, tBu). MS (NOBA,
FABϾ0): 273–275, [MϩH]ϩ. Anal (C8H17ClN2O4S): calcd
% C 35.23 H 6.23; N 10.27; found % C 35.29; H 6.26; N
10.23.
N1-BOC,N3,N3-bis(2-chloroethyl) sulfamide 18. Yield85%;
Rf0.88 (CH2Cl2–MeOH 95:5); Mp: 83–84ЊC; IR (KBr, n
cmϪ1): 3300 (NH), 1710 (CyO), 1360 and 1145 (SO2).1H
NMR (CDCl3, d): 7.30 (s, 1H, exch, NH), 3.79 (m, 8H,
2×CH2CH2Cl), 1.54 (s, 9H, tBu). MS (NOBA, FABϾ0):
320, 322, 324 [MϩH]ϩ (C9H18Cl2N2O4S).
N2-BOC-N5-methyl-1,2,5-thiadiazolidine 1,1-dioxide 24.
5 g (22.32 mmol) of 11 in 10 mL of anhydrous CH2Cl2 are
added dropwise to a solution of triphenylphosphine (8.75 g,
33.48 mmol) and diisopropylazodicarboxylate (DIAD)
(6.77 g, 33.48 mmol) in the same solvent. The reaction
medium was stirred under atmosphere of dry nitrogen for
20 min. Oxidoreduction products were removed by filtration
after precipitation with diethyl ether. The filtrate was
concentrated and the residue was purified by column chro-
matography eluted with CH2Cl2. Cyclic sulfamide 24 was
obtained as a white solid.
N1-BOC,N3-methyl,N3-(2-chloroethyl) sulfamide 19.
Yield96%; Rf0.76 (CH2Cl2–MeOH 95:5); IR (KBr, n
1
cmϪ1): 3225 (NH), 1705 (CyO), 1335 and 1153 (SO2). H
NMR (CDCl3, d): 7.05 (s, 1H, exch, NH), 3.62 (s, 4H,
2×CH2), 2.98 (s, 3H, CH3), 1.44 (s, 9H, tBu). MS
(NOBA, FABϾ0): 273–275, [MϩH]ϩ; 237; 172
(C8H17ClN2O4S).
Yield90%; Rf0.77 (CH2Cl2–MeOH 95:5); Mp: 84ЊC; IR
(KBr, n cmϪ1): 1705 (CyO), 1310 and 1170 (SO2). 1H NMR
(CDCl3, d): 3.76 (t, 2H, CH2), 3.28 (t, 2H, J6.43 Hz, CH2),
3.46 (s, 3H, CH3), 1.48 (s, 9H, tBu). MS (NOBA, FABϾ0):
237, [MϩH]ϩ; 136. Anal (C8H16N2O4S).
N1-BOC,N3-[(2-chloro-1-isobutyl) ethyl] sulfamide 20.
Yield90%; Rf0.80 (CH2Cl2–MeOH 95:5); Mp: 165ЊC;
IR (KBr, n cmϪ1): 3330 and 3225 (NH), 1700 (CyO), 1355
1
and 1163 (SO2). H NMR (CDCl3, d): 7.24 (s, 1H, exch,
N2-BOC-N5-(2-chloroethyl)-1,2,5-thiadiazolidine 1,1-diox-
ide 25. Yield96%; Rf0.70 (CH2Cl2–MeOH 95:5); Mp:
NHBOC), 5.28 (d, 1H, exch, NH) 3.76 (m, 2H, CH2Cl), 3.64