10014
T. Mizuno et al. / Tetrahedron 58 (2002) 10011–10015
(or carbonyl sulfide) and the esterification using methyl
iodide, followed by the chlorination with sulfuryl chloride.
2.37 (s, 3H), 5.34 (s, 2H), 7.17–7.42 (m, 3H), 7.56–7.59
1
3
(m, 1H); C NMR (75 MHz, CDCl ) d13.5, 68.2, 123.3,
3
1
27.5, 129.9, 129.9, 132.8, 134.7, 171.4; MS (m/z, %) 262
þ
From the viewpoint of application to actual industrial
production of CbzCl (1a) as an N-protective reagent for
amino groups in peptide synthesis, the present method for
synthesis of CbzCl (1a) in the absence of phosgene is very
significant, in terms of the use of easily available carbon
monoxide or carbonyl sulfide as carbonyl source, and
industrially acceptable reaction conditions.
(1), 260 (M , 1), 181 (61), 171 (97), 169 (100), 90 (14), 89
(9). Exact MS calcd for C H O BrS: 259.9507. Found:
259.9515.
9
9 2
4.1.4. S-Methyl O-p-methoxybenzyl carbonothioate (3d).
IR (neat) 1710, 1135 cm2 ; H NMR (300 MHz, CDCl ) d
1 1
3
2.34 (s, 3H), 3.81 (s, 3H), 5.18 (s, 2H), 6.89 (d, J¼9 Hz,
1
3
2
1
H), 7.30 (d, J¼9 Hz, 2H); C NMR (75 MHz, CDCl ) d
3
35.5, 55.3, 68.9, 114.0, 127.4, 130.3, 159.9, 171.6; MS
þ
4. Experimental
(m/z, %) 212 (M , 28), 168 (6), 122 (9), 121 (100), 77 (5).
Exact MS calcd for C H O S: 212.0507. Found:
212.0469.
1
0 12 3
4
.1. General
FT-IR spectra were recorded on a Nicolet Magna-IR 550
4.1.5. S-Methyl O-phenyl carbonothioate (7a). IR (neat)
21
1
13
1
instrument. H and C NMR spectra were obtained on a
JEOL JNM-AL300 (300 MHz, 75 MHz) instrument.
Chemical shifts were reported in ppm relative to tetra-
methylsilane (d-units). Mass and exact mass spectra were
recorded on a JEOL JMS-600 spectrometer. Benzyl
alcohols (2a–d), phenol (5a), methyl iodide, ethyl iodide,
THF, DBU, bases, sulfur (99.5%), carbon monoxide
1730, 1110 cm
; H NMR (300 MHz, CDCl ) d 2.42
3
(s, 3H), 7.15 (d, J¼8 Hz, 2H), 7.24 (t, J¼8 Hz, 1H), 7.38
1
3
(t, J¼8 Hz, 2H); C NMR (75 MHz, CDCl
) d 13.6, 121.2,
126.1, 129.4, 151.2, 170.7; MS (m/z, %) 168 (M , 27), 140
3
þ
(100), 75 (92). Exact MS calcd for C
Found: 168.0210.
H O S: 168.0245.
8 8 2
(99.9%), carbonyl sulfide (96%), and sulfuryl chloride
were used as purchased.
4.2. Typical procedure for the synthesis of S-methyl
O-benzyl carbonothioate (3a) by the carbonylation with
carbonyl sulfide
4
.1.1. Typical procedure for the synthesis of S-methyl
O-benzyl carbonothioate (3a) from carbon monoxide
and sulfur. In a 100 mL stainless steel autoclave, benzyl
alcohol (2a) (1.03 mL, 10 mmol), powdered sulfur (481 mg,
A THF solution (50 mL) containing benzyl alcohol (2a)
(10.3 mL, 100 mmol) and DBU (22.4 mL, 150 mmol) was
vigorously stirred under carbonyl sulfide (0.1 MPa) at 208C
for 1 h. Into the THF solution of carbonothioate salt, methyl
iodide (7.5 mL, 120 mmol) was added slowly at 08C under
argon atmosphere. The reaction mixture was stirred for
additional 2 h at 208C. The resulting mixture was then
poured into 1N HCl (100 mL), and extracted with t-butyl
methyl ether (100 mL£3). After evaporation of solvents and
purification by vacuum distillation, S-methyl O-benzyl
carbonothioate (3a) was obtained in 87% yield (15.76 g).
1
5 mmol), DBU (2.24 mL, 15 mmol), and THF (10 mL)
were placed with a magnetic stirring bar under an argon
atmosphere. The autoclave was then flushed three times
with carbon monoxide and finally charged with carbon
monoxide at 1.0 MPa at 208C. The reaction was carried
out at 808C for 6 h with vigorous stirring. After cooling
down and evacuation of carbon monoxide, methyl iodide
(
0.93 mL, 15 mmol) was added at 08C under argon
atmosphere. The reaction mixture was stirred for additional
6 h under ambient pressure, at 208C. Then, the resulting
1
4.2.1. S-Ethyl O-benzyl carbonothioate (3e). IR (neat)
) d 1.32 (t,
1710, 1135 cm2 ; H NMR (300 MHz, CDCl
1
1
mixture was poured into 1N HCl (100 mL), and extracted
with t-butyl methyl ether (100 mL, 50 mL£3). After
evaporation of solvents and purification by short-
column chromatography (silica gel, toluene–AcOEt¼1:1),
S-methyl O-benzyl carbonothioate (3a) was afforded in 89%
3
J¼7 Hz, 3H), 2.88 (q, J¼7 Hz, 2H), 5.24 (s, 2H), 7.35 (s,
1
3
5H); C NMR (75 MHz, CDCl
128.4, 128.6, 135.3, 171.1; MS (m/z, %) 196 (M , 23), 92
) d 14.9, 25.4, 68.7, 128.3,
3
þ
(17), 91 (100), 77 (7), 65 (9). Exact MS calcd for
2
5
yield (1.62 g). S-Methyl O-benzyl carbonothioate (3a): IR
2
C H O S: 196.0558. Found: 196.0548.
10 12 2
1
1
(
neat) 1710, 1135 cm ; H NMR (300 MHz, CDCl ) d
3
1
3
2
CDCl ) d 13.4, 68.9, 128.4, 128.5, 135.2, 171.6; MS (m/z, %)
.35 (s, 3H), 5.24 (s, 2H), 7.36 (s, 5H); C NMR (75 MHz,
4.2.2. General procedure for the synthesis of CbzCl (1a)
by the chlorination of 3a with sulfuryl chloride. Into neat
S-methyl O-benzyl carbonothioate (3a) (3.64 g, 20 mmol),
sulfuryl chloride (2.41 mL, 30 mmol) was added slowly at
3
þ
calcd for C H O S: 182.0402. Found: 182.0368.
1
82 (M , 69), 92 (48), 91 (100), 77 (27), 65 (36). Exact MS
9
10 2
0
8C under argon atmosphere. The reaction mixture was
stirred for additional 1 h at 208C. After evaporation of
volatile compounds (SO Cl and MeSCl), CbzCl (1a) was
4
IR (neat) 1715, 1145 cm ; H NMR (300 MHz, CDCl ) d
.1.2. S-Methyl O-o-chlorobenzyl carbonothioate (3b).
2
1 1
3
2
2
2
.37 (s, 3H), 5.36 (s, 2H), 7.26–7.30 (m, 2H), 7.37–7.43
1
given in 100% yield (3.41 g) in an almost pure form.
After further purification by vacuum distillation accom-
panied with a partial decomposition, 1a was obtained in
3
(
m, 2H); C NMR (75 MHz, CDCl ) d 13.5, 66.0, 126.9,
3
1
29.5, 129.7, 129.8, 133.0, 133.6, 171.4; MS (m/z, %) 218
þ
C H O ClS: 216.0012. Found: 216.0002.
21
(
5), 216 (M , 13), 127 (36), 125 (100). Exact MS calcd for
72% yield (2.47 g). CbzCl (1a): IR (neat) 1780, 1145 cm
1
;
H NMR (300 MHz, CDCl ) d 5.30 (s, 2H), 7.40 (s, 5H);
3
9
9 2
1
3
C NMR (75 MHz, CDCl ) d 73.4, 128.8, 128.9, 129.3,
3
þ
4
IR (neat) 1715, 1140 cm ; H NMR (300 MHz, CDCl ) d
.1.3. S-Methyl O-o-bromobenzyl carbonothioate (3c).
2
133.3, 150.6; MS (m/z, %) 172 (28), 170 (M , 80), 91 (100),
26
90 (35).
1
1
3