SHORT PAPER
Alkyl Bromides from Thiocarbamates
3567
O-6-Hydroxyhexyl Dimethylcarbamothioate (1e)
In conclusion, the conversion of 1 into 3 is an attractive
method for converting primary alcohols that have been
protected as dimethylthiocarbamate directly into bro-
mides. A separate deprotection step is avoided. The reac-
tion is reasonably chemoselective, but it does not work
well with acid-sensitive or nucleophilic groups.
Method A7 using hexane-1,6-diol (3.5 equiv) to favor monosubsti-
tution; yield: 57%; bp 143–144 °C/0.4 mbar.
1H NMR (400 MHz, CDCl3): d = 4.44 (t, J = 6.6 Hz, 2 H), 3.65 (t,
J = 6.6 Hz, 2 H), 3.36 (s, 3 H), 3.11 (s, 3 H), 1.75 (m, 2 H), 1.59 (m,
2 H), 1.42 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 188.43, 71.77, 62.98, 42.83,
37.88, 32.81, 28.94, 25.98, 25.63.
Dimethythiocarbamates 1a–j (Scheme 1) were prepared using the
methods described by Falck and co-workers.7 The bromides 3a–j
are all known compounds, and they show NMR and MS data con-
sistent with their structures. Product yields are listed in Table 1. In
those cases where only the alkyl bromide 3 was produced, the purity
was greater than 97% by GC/MS.
HRMS: m/z [M + Na]+ calcd for C9H19NNaO2S: 228.10287; found:
228.10235.
6-(Dimethylcarbamothioyloxy)hexyl Acetate (1f)
From the reaction of 1e with Ac2O and pyridine; yield: 50%; bp
165–169 °C/0.4 mbar.
1H NMR (400 MHz, CDCl3): d = 4.44 (t, J = 6.6 Hz, 2 H), 4.06 (t,
J = 6.6 Hz, 2 H), 3.37 (s, 3 H), 3.11 (s, 3 H), 2.05 (s, 3 H), 1.74 (m,
2 H), 1.65 (m, 2 H), 1.42 ( m, 4 H).
O-Hex-5-enyl Dimethylcarbamothioate (1a)
Method B7 using 6-bromohex-1-ene; yield: 69%; bp 93–94 °C/0.4
mbar.
1H NMR (400 MHz, CDCl3): d = 5.80 (ddt, J = 17.1, 10.2, 6.7 Hz,
1 H), 5.02 (dd, J = 17.1, 2.1 Hz, 1 H), 5.97 (dd, J = 10.2, 2.1 Hz, 1
H), 4.44 (t, J = 6.5 Hz, 2 H), 3.35 (s, 3 H), 3.10 (s, 3 H), 2.10 (td,
J = 7.9, 6.7 Hz, 2 H), 1.74 (tt, J = 6.9, 6.5 Hz, 2 H), 1.50 (tt, J = 7.9,
6.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 188.39, 171.33, 71.67, 64.58,
42.83, 37.88, 28.86, 28.70, 25.84, 25.82, 21.24.
HRMS: m/z [M + Na]+ calcd for C11H21NNaO3S: 270.11344; found:
270.11273.
13C NMR (100 MHz, CDCl3): d = 188.44, 138.52, 114.99, 71.73,
O-6-(Benzyloxy)hexyl Dimethylcarbamothioate (1g)
Method B7 using 6-(benzyloxy)hexan-1-ol (the latter was made
from the reaction of hexane-1,6-diol with BnCl and KOH) followed
by chromatography (silica gel); yield: 89%.
1H NMR (400 MHz, CDCl3): d = 7.34 (m, 5 H), 4.5 (s, 2 H), 4.43 (t,
J = 6.6 Hz, 2 H), 3.47 (t, J = 6.5 Hz, 2 H), 3.36 (s, 3 H), 3.09 (s, 3
H), 1.73 (m, 2 H), 1.63 (m, 2 H), 1.42 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 188.49, 138.77, 128.54, 127.8,
127.68, 73.12, 71.89, 70.49, 42.85, 37.9, 29.93, 28.98, 26.17, 26.12.
HRMS: m/z [M + Na]+ calcd for C16H25NNaO2S: 318.14982; found:
318.14971.
42.85, 37.90, 33.53, 28.45.
HRMS: m/z [M + Na]+ calcd for C9H17NNaOS: 210.09231; found:
210.09223.
O-6-Oxohexyl Dimethylcarbamothioate (1b)
From CrO3 oxidation of 1e,7 followed by chromatography (silica
gel); yield: 44%.
1H NMR (400 MHz, CDCl3): d = 9.78 (t, J = 1.6 Hz, 1 H), 4.45 (t,
J = 6.7 Hz, 2 H), 3.36 (s, 3 H), 3.12 (s, 3 H), 2.47 (td, J = 7.2, 1.6
Hz, 2 H), 1.76 (m, 2 H), 1.69 (m, 2 H), 1.44 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 202.36, 188.28, 71.42, 43.97,
42.91, 37.95, 28.83, 25.82, 21.97.
HRMS: m/z [M + Na]+ calcd for C9H17NNaO2S: 226.08722; found:
226.08707.
O-6-(Tetrahydro-2H-pyran-2-yloxy)hexyl Dimethylcarbamo-
thioate (1h)
From the reaction of 1e with tetrahydropyran and TsOH, followed
by chromatography (silica gel); yield; 77%.
1H NMR (400 MHz, CDCl3): d = 4.57 (m, 1 H), 4.43 (t, J = 6.6 Hz,
2 H), 3.87 (m, 1 H), 3.74 (m, 1 H), 3.50 (m, 1 H), 3.39 (m, 1 H), 3.37
(s, 3 H), 3.11 (s, 3 H), 1.90–1.48 (m, 10 H), 1.43 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 188.45, 99.08, 71.89, 67.67,
62.61, 42.84, 37.9, 30.99, 29.89, 28.96, 26.2, 26.1, 25.71, 19.95.
HRMS: m/z [M + Na]+ calcd for C14H27NNaO3S: 312.16039; found:
312.15972.
O-6-Oxoheptyl Dimethylcarbamothioate (1c)
Method B7 using 7-hydroxyheptan-2-one (the latter was made from
the reaction of e-caprolactone with MeLi); yield: 30%; bp 145–146
°C/0.4 mbar.
1H NMR (400 MHz, CDCl3): d = 4.43 (t, J = 6.6 Hz, 2 H), 3.36 (s,
3 H), 3.11 (s, 3 H), 2.45 (t, J = 7.4 Hz, 2 H), 2.14 (s, 3 H), 1.74 (m,
2 H), 1.62 (m, 2 H), 1.40 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 208.86, 188.28, 71.56, 43.73,
42.88, 37.94, 30.20, 28.86, 25.80, 23.66.
HRMS: m/z [M + Na]+ calcd for C10H19NNaO2S: 240.10287; found:
240.10237.
O-6-(tert-Butyldimethylsiloxy)hexyl Dimethylcarbamothioate
(1i)
Method B7 using 6-(tert-butyldimethylsiloxy)hexan-1-ol (the latter
was made from the reaction of hexane-1,6-diol with NaH, then with
TMDMSCl) followed by chromatography (silica gel); yield: 99%.
Methyl 6-(Dimethylcarbamothioyloxy)hexanoate (1d)
Method B7 using methyl 6-hydroxyhexanoate (the latter was made
from the reaction of e-caprolactone with methanolic H2SO4); yield:
42%; bp 155–160 °C/0.4 mbar.
1H NMR (400 MHz, CDCl3): d = 4.44 (t, J = 6.5 Hz, 2 H), 3.67 (s,
3 H), 3.36 (s, 3 H), 3.10 (s, 3 H), 2.33 (t, J = 7.5 Hz, 2 H), 1.75 (m,
2 H), 1.68 (m, 2 H), 1.44 (m, 2 H).
1H NMR (400 MHz, CDCl3): d = 4.43 (t, J = 6.6 Hz, 2 H), 3.61 (t,
J = 6.4 Hz, 2 H), 3.37 (s, 3 H), 3.11 (s, 3 H), 1.73 (tt, J = 7.4, 6.6 Hz,
2 H), 1.53 (tt, J = 7.1, 6.4 Hz, 2 H), 1.39 (m, 4 H), 0.89 (s, 9 H), 0.05
(s, 6 H).
13C NMR (100 MHz, CDCl3): d = 188.48, 71.94, 63.32, 42.85, 37.9,
32.97, 29.04, 26.22, 26.07, 25.77, 18.63, –5.00.
13C NMR (100 MHz, CDCl3): d = 188.45, 174.07, 71.55, 51.71,
42.86, 37.88, 34.15, 28.70, 25.80, 24.83.
HRMS: m/z [M + Na]+ calcd for C15H33NNaO2SSi: 342.18935;
found: 342.18884.
HRMS: m/z [M + Na]+ calcd for C10H19NNaO3S: 256.09779; found:
256.09716.
Synthesis 2008, No. 22, 3565–3568 © Thieme Stuttgart · New York