J . Org. Chem. 1997, 62, 4539-4540
4539
Ta ble 1. P r ep a r a tion of Va r iou s Isoth iocya n a tes
An Im p r oved P r oced u r e for th e
P r ep a r a tion of Isoth iocya n a tes fr om
P r im a r y Am in es by Usin g Hyd r ogen
P er oxid e a s th e Deh yd r osu lfu r iza tion
Rea gen t
reactant (mmol)
tempa
starting
isolated
material amine CS2 base H O2 (°C) product yield (%)
2
100 500 100b
1
a
1b
c
d
300 30-40
340 20-30
4a
4b
4c
4d
93
92
95
84
57 340 110b
d
1
1
75 360
7.5c 210 0-10
100 100 100c
100 0-10
Ge Li,* Hirokuni Tajima, and Takahito Ohtani
a
Dehydrosulfurization temperature. b NaOH was used, and the
solvent contained 10% of water. c Triethylamine was used. R )
SCNCH2(CH)4CH2.
d
Fukui Research Laboratory, Rengo Co., Ltd., 10-8-1
J iyugaoka, Kanazu-Cho, Sakai-Gun, Fukui 919-06, J apan
Received J anuary 21, 1997
The use of hydrogen peroxide as a dehydrosulfurization
reagent in the preparation of alkyl isothiocyanate was
1
first reported by J ohar et al. in 1970. In their experi-
ments, isothiocyanate was made in one step by reacting
hydrogen peroxide with a mixture of primary amine and
carbon disulfide in the presence of a secondary aliphatic
amine. No heating was required and the total reaction
time was less than 10 min. Although it was a simple,
rapid, and economical process, the yield was only moder-
ate for aliphatic isothiocyanates and very low for aro-
matic isothiocyanates. It was also pointed out that this
method failed to prepare diisothiocyanates.
2
It was claimed in 1972 in a German patent that alkyl
isothiocyanates could be made in 70-95% yield by
reacting hydrogen peroxide with the corresponding pri-
mary amines and carbon disulfide in an aqueous solution.
Instead of secondary aliphatic amine, NaOH was used
as the base. The reaction temperature and the pH of the
solution were controlled at 80-120 °C and 5-9, respec-
tively.
Thiuram disulfide, despite its very low concentration,
is confirmed to exist in the reaction mixture through
monitoring the whole reaction process with HPLC. In
an independent experiment, hydrogen peroxide is added
to a thiuram disulfide solution, and the yield of isothio-
cyanate is found to be about 90%, which strongly sup-
ported our above proposal.
A similar mechanism was mentioned by Giesselmann
et al. in their review5 that isothiocyanation passed
through thiuram disulfide. It was described, however,
that thiuram disulfide decomposed to the corresponding
These two works, to the best of our knowledge, are the
only ones involving hydrogen peroxide in the synthesis
of isothiocyanates from primary amines. In our attempts
to synthesize hydroxyalkyl isothiocyanates from the
corresponding amino alcohols, we found that the methods
mentioned above did not result in any desired products.3
Further, we were unable to reproduce the experiments
isothiocyanate and H S that was subsequently oxidized
2
4
described in the German patent.
by hydrogen peroxide to either Na SO4 or Na S O
3
2
2
2
In this paper we will report a modified method that
has been proven to be very efficient for the preparation
of not only alkyl isothiocyanates, but diisothiocyanates,
hydroxyl isothiocyanates, and some aromatic isothiocy-
anates as well (Table 1). This method consists of the
reaction of hydrogen peroxide with a mixture of primary
amine, carbon disulfide, and base in an organic solvent
that is essentially miscible with water. Excess carbon
disulfide is generally required. Various bases, including
NaOH, ammonia, triethylamine (TEA), etc., can be used.
In preparing hydroxyl isothiocyanates, only a catalytic
amount of base should be used in order to minimize the
inter- and/or intramolecular condensation. The reaction
temperature is generally kept below 15 °C but can be
slightly higher in some cases. In any case, reaction
temperatures exceeding 50 °C should be avoided.
depending on the oxidant amount. Although we also
observed that thiuram disulfide slowly decomposed to
isothiocyanate when standing at room temperature, it
was evident that H
no black PbS solid was generated when thiuram disulfide
was mixed with Pb(NO in an aqueous solution. As a
2
S did not exist in the system since
3 2
)
result we want to point out here that their proposal
seems very unlikely.
Exp er im en ta l Section
Gen er a l P r oced u r e for th e P r ep a r a tion of Isoth iocy-
a n a tes 4a -d . To a stirred solution of amine 1 (∼0.1 mol) and
base (0.1-2 equiv) in a THF solution (100 mL) was added carbon
disulfide (1-5 equiv) with ice cooling. Agitation was continued
for 0.5 h followed by dropwise addition of hydrogen peroxide
(30%, 1-6 equiv) with the reaction temperature being controlled
at 0-40 °C. The reaction mixture was neutralized with hydro-
chloric acid, evaporated under reduced pressure, and extracted
with ethyl acetate. Removing the ester by evaporation under
reduced pressure resulted in a yellowish oily residue. Purifica-
tion was carried out by distillation in vacuo or liquid chroma-
tography on a silica gel column, except as mentioned otherwise.
The isothiocyanation is proposed to pass through
thiuram disulfide as shown in the following equations:
(
1) J ohar, G. S.; Agarwala, U.; Rao, P. B. Indian J . Chem. 1970, 8,
7
9
59.
(
(
(
2) Schwarze, W.; Weigert, W. DE 2,105,473, 1971.
3) Tajima, H.; Li, G. J apanese Patent Application 96-9985, 1996.
4) Li, G.; Tajima, H.; Ohtani, T. J apanese Patent Application 96-
(5) Giesselmann, V. G.; Huthmacher, K.; Klenk, H.; Romanowski,
F. Chem. Z. 1990, 114, 215.
975, 1996.
S0022-3263(97)00100-X CCC: $14.00 © 1997 American Chemical Society
Li, Ge
