Jan-Feb 2004
Simple And Efficient Cleavage Reaction of The Boc Group
59
1
1H), 3.90 (d, J=6.3 Hz, 2H), 3.50-3.30 (2dd, J=3.9, 6.8 Hz, 2H),
2.55 (m, 1H), 1.50 (m, 2H); 1.35 (m, 1H); 0.90 (d, 6H, J=6.1 Hz);
ms (NOBA, FAB>0): 263 [M+H]+, 91, (M=262-264).
3325 (NH) and 3430 (OH); H nmr (deuteriochloroform): δ 7.34
(m, 5H), 5.80 (m, 1H), 4.00 (d, J=6.2 Hz, 2H), 3.80-3.30 (2dd, J=
3.8, 6.7 Hz), 2.80 (m, 1H), 2.30 (s, 1H), 2.10 (m, 1H), 0.95 (2d,
J=6.7 Hz, 6H); ms (NOBA, FAB>0): 194 [M+H]+, 91, (M=193).
A n a l. Calcd. for C
Found: C, 59.57; H, 8.03; N, 5.31.
H Cl N: C, 59.54; H, 8.01; N, 5.34.
13 21 2
Anal. Calcd. for C
C, 74.65; H, 9.87; N, 7.21.
H
NO: C, 74.61; H, 9.84; N, 7.25. Found:
13 21
N-Benzyl-N-(2-chloro-1-benzylethyl)aminechlorhydrate (4b).
N-Benzyl-leucinol (3a).
This compound was obtained in 58% yield; Mp =145-147 °C;
1
[α] =-65 (c=1, CHCl ); ir (potassium bromide): ν cm- : 3234
(NH); H nmr (deuteriochloroform): δ 7.45 (m, 10H), 5.50 (m,
1H), 4.32 (d, J=6.3 Hz, 2H), 3.68-3.26 (2dd, J=3.9, 6.8 Hz, 2H),
2.55 (m, 1H), 3.20-3.50 (2dd, J=6.4, 6.1, 16.3 Hz, 2H), 2.95 (m,
1H); ms (NOBA, FAB>0): 297 [M+H]+, 91, (M=296-298).
This compound was obtained in 84% yield; R =0.32 (CH Cl -
D
3
f
MeOH, 95-5); oil; [α] =+105 (c=1, CHCl ); ir (film, CCl ): ν
2
2
1
D
3
4
-1
1
cm : 3320 (NH) and 3400 (OH); H nmr (deuteriochloroform):
δ 7.64 (m, 5H), 5.70 (m, 1H), 3.90 (d, J=6.2 Hz, 2H), 3.70-3.20
(2dd, J= 3.9, 6.7 Hz, 2H), 2.00 (s, 1H), 1.50 (m, 2H), 1.35 (m,
1H); 0.90 (d, J=6.1 Hz, 6H); ms (NOBA, FAB>0): 208 [M+H]+,
91, (M=207).
A n a l. Calcd. for C H Cl N: C, 64.86; H, 6.42; N, 4.73.
16 19 2
Found: C, 64.90; H, 6.45; N, 4.68.
Anal. Calcd. for C H NO: C, 75.36; H, 10.14; N, 6.76.
13 21
Found: C, 75.39; H, 10.16; N, 6.71.
2
5
General Procedure for Preparation of N -Boc-N -benzyl-4-sub-
stituted-1,2,5-thiadiazolidine 1,1-Dioxides (1c-4c).
N-Benzyl-phenylalaninol (4a).
To a strirred solution of (5 mL, 8.15 g, 57.4 mmol) of chloro-
sulfonyl isocyanate (CSI) in 100 mL of anhydrous
dichloromethane at 0 °C were added (4.24 g, 57.4 mmol) of
absolute tert-butylalcohol in the same solvent. After being
strirred for 30 min, the resulting solution of Boc-sulfamoyl chlo-
ride and 24 mL of triethylamine (17.40 g, 171.8 mmol) in 100
mL of dichloromethane was added drop wise to a 57.4 mmol
solution of N-benzyl-4-chloroalkylamine hydrochlorides in 125
mL of dichloromethane. The reaction temperature did not rise
above 5°C. The resulting solution was allowed to warm up to rt
over 2 h. The reaction mixture was diluted with 100 mL of
dichloromethane, washed with HCl 0.1 N solution and brine. The
organic layer was dried (Na SO ) and concentrated in vacuo, the
This compound was obtained in 80% yield; R =0,28 (CH Cl -
f
MeOH, 95-5); Mp =67-69°; [α] =+55 (c=1, CHCl ); ir (potas-
2
2
D
3
-1
1
sium bromide): ν cm : 3315 (NH) and 3390 (OH); H nmr (deu-
teriochloroform): δ 7.20 (m, 10H), 5.80 (m, 1H), 4.10 (d, J=6.2
Hz, 2H), 3.80-3.30 (2dd, J= 3.9, 6.7 Hz, 2H), 3.20-3.50 (ddd,
J=6.4, 6.1, 16.3 Hz, 2H), 2.20 (s, 1H); ms (NOBA, FAB>0): 242
[M+H]+, 91, (M=241).
Anal. Calcd. for C
C, 79.69; H, 7.90; N, 5.75.
H NO: C, 79.66; H,7.88; N, 5.80. Found:
16 19
Substituted Mustards (1b-4b).
To a refluxing solution of N-benzylaminoalcohol (14.60
mmol) in CHCl (50 mL) was slowly added a solution of thionyl
2
4
residue was purified by flash chromatography. Elution with
CH Cl /MeOH (95:5) gave cyclic sulfamides in 75-80% yield as
colorless solids.
3
chloride (60 mL, 126 mmol) in 30 mL of CHCl . When the addi-
2
2
3
tion was completed, the reflux was continued for 2 h. The reac-
tion mixture was concentrated in vacuo to give the crude product
as white powder in good yields.
2 5
N -Boc-4-methyl-N -benzyl-1,2,5-thiadiazolidine 1,1-Dioxide (1 c).
This compound was obtained in 77% yield; R =0,72 (CH Cl -
f
MeOH, 95-5); Mp= 95-97°C; [α] =+25 (c=1, CHCl ); ir (potas-
2
2
N-Benzyl-N-(2-chloro-1-methylethyl)aminechlorhydrate (1b).
D
3
sium bromide): ν cm- :1708 (C=O); 1330 and 1150 (SO ); H
1
1
This compound was obtained in 60% yield; Mp =145-146 °C;
1
[α] =-17 (c=1, CHCl ); ir (potassium bromide): ν cm- : 3275
2
nmr (deuteriochloroform): δ 7.40 (m, 5H), 4.30 (2d, J=15.2 Hz,
1H), 3.88 and 3.50 (2dd, J= 2.7, 5.6 Hz, 2H), 3.50 (m, 1H), 1.58
(s, 9 H), 1.25 (d, J=6.9 Hz, 3H); ms (NOBA, FAB>0): 327
[M+H]+, 226, 91, (M=326).
D
3
1
(NH); H nmr (deuteriochloroform): δ 7.26 (m, 5H), 6.10 (m,
1H), 4.10 (d, J=6.15 Hz, 2H), 3.70-3.50 (2dd, J=3.9, 6.8 Hz, 2H),
2.70 (m, 1H), 1.25 (d, J=6.9 Hz, 3H); ms (NOBA, FAB>0): 221
[M+H]+, 91, (M=220-222).
A n a l. Calcd. for C
H N O S: C, 55.21; H, 6.75; N, 8.59.
15 22 2 4
Found: C, 55.30; H, 6.73; N, 8.51.
A n a l. Calcd. for C
Found: C, 54.59; H, 6.85; N, 6.30.
H Cl N: C, 54.54; H, 6.81; N, 6.36.
10 15 2
2
5
N -Boc-4-isopropyl-N -benzyl-1,2,5-thiadiazolidine 1,1-Dioxide
(2c).
N-Benzyl-N-(2-chloro-1-isopropylethyl)aminechlorhydrate (2b).
This compound was obtained in 58% yield; Mp=126-128 °C;
This compound was obtained in 75% yield; R =0,72 (CH Cl -
f
2
2
MeOH, 95-5); Mp =82-84°C; [α] =+5 (c=1, CHCl ); ir (potas-
1
[α] =-27, (c=1, CHCl ); ir (potassium bromide): ν cm- :3265
D
sium bromide): ν cm- 1710 (C=O); 1340 et 1160 (SO ) H nmr
3
D
3
1
1
1
(NH); H nmr (deuteriochloroform): δ 7.65 (m, 5H), 6.10 (m,
1H), 4.05 (d, J=6.15 Hz, 2H), 3.60-3.40 (2dd, J=3.9, 6.8 Hz, 2H),
2.65 (m, 1H), 2.10 (m, 1H), 0.95 (2d, J=6.7 Hz, 6H); ms (NOBA,
FAB>0): 249 [M+H]+, 91, (M=248-250).
2
(deuteriochloroform): δ 7.40 (m, 5H), 4.30 (dd, J=14.6 Hz),
3.90–35.50 (2dd, J= 3.2, 6.7 Hz, 1H), 3.50 (m, 1H), 1.58 (s+m,
10 H), 0.97-1.05 (2d, J= 6.9 Hz, 6H); ms (NOBA, FAB>0): 355
[M+H]+, 91, 254, (M=354).
A n a l. Calcd. for C H Cl N: C, 58.06; H, 7.66; N, 5.64.
12 19 2
Found: C, 58.10; H, 7.71; N, 5.59.
A n a l. Calcd. for C
H N O S: C, 57.62; H,7.34; N, 7.91.
17 26 2 4
Found: C, 57.55; H, 7.41; N, 7.85.
N-Benzyl-N-(2-chloro-1-isobutylethyl)aminechlorhydrate (3b).
This compound was obtained in 58% yield; Mp =132-134 °C;
2
N -Boc-4-isobutyl-N -benzyl-1,2,5-thiadiazolidine 1,1-dioxide (3c).
5
1
[α] =-142 (c=1, CHCl ); ir (potassium bromide):ν cm- : 3274
This compound was obtained in 78% yield; R =0,69 (CH Cl -
f
MeOH, 95-5); Mp = 87-89 °C; [α] =-3 (c=1, EtOH); ir (potassium
2
2
D
(NH); H nmr (deuteriochloroform): δ 7.45 (m, 5H), 5.80 (m,
3
1
D