Synthesis of thiocarbamates from thiols and isocyanates under catalyst- and solvent-free conditions

Article abstract of DOI:10.1007/s00706-007-0762-7

A simple and efficient procedure was developed for the synthesis of S-alkyl (aryl) thiocarbamates under solvent-free conditions without the use of a catalyst. The significant features of this protocol are (a) operational simplicity, (b) mild reaction cond

Full text of DOI:10.1007/s00706-007-0762-7

Monatshefte fu¨r Chemie 139, 137–140 (2008)
DOI 10.1007/s00706-007-0762-7
Printed in The Netherlands
Synthesis of Thiocarbamates from Thiols and Isocyanates
Under Catalyst- and Solvent-Free Conditions
Barahman Movassagh1;2;ꢀ and Mohammad Soleiman-Beigi1
1
Department of Chemistry, K.N. Toosi University of Technology, Tehran, Iran
2
Kermanshah Oil Refining Company, Kermanshah, Iran
Received June 30, 2007; accepted July 4, 2007; published online January 11, 2008
# Springer-Verlag 2008
Summary. A simple and efficient procedure was developed
alkyl and aryl thiocyanates [17]. Several other meth-
for the synthesis of S-alkyl (aryl) thiocarbamates under sol-
vent-free conditions without the use of a catalyst. The signifi-
cant features of this protocol are (a) operational simplicity, (b)
mild reaction conditions, (c) short reaction times, (d) solvent-
free conditions, and (e) high product yields.
ods have been reported for the preparation of thiocar-
bamates; however, most require the preparation of
complex starting materials and multistep approaches,
among them: reaction of amines and thiols in the
presence of carbon monoxide under (PPh3)2NiBr2
and (PPh3)2NiCl2 catalysts [18], DBU-assisted car-
bonylation of amines with carbon monoxide and sul-
fur [19], carbamoylation of thiols using carbamoyl
imidazolium salts [20], reaction of elemental sulfur
with carbon monoxide and alkyl amines in the pres-
ence of catalytic amount of selenium and subsequent
addition of primary alkyl halides [21]. Other groups
[2, 13] have prepared these compounds from con-
densation of gaseous carbonyl sulfide (COS) with a
secondary amine in the presence of a base. N,N-
Disubstituted S-alkyl thiocarbamates have also been
prepared from salts of dithiocarbamic acid, which
are prepared by the addition of secondary amines to
carbon disulfide [22]. Recently, Wynne and co-work-
ers [23] reported two approaches for the synthesis
of S-alkyl thiocarbamates using trichloroacetyl chlo-
ride. Thiocarbamates have also been prepared from
asymmetrical disulfides in two steps [24]; in the first
step, disulfides were converted into the correspond-
ing thiols, and finally the thiols reacted with iso-
cyantes to afford thiocarbamates in good yields. In
a recent report [25], we described a protocol for the
synthesis of thiocarbamates from isocyanates and
disulfides in the presence of the Zn=AlCl3 system.
Keywords. Thiocarbamates; Thiols; Isocyanates; Solvent-
free; Catalyst-free.
Introduction
Thiocarbamates, especially S-alkyl thiocarbamates
(S-alkyl thiourethanes), are an important class of
compounds that have numerous biological effects
ranging from pesticidal [1, 2], fungicidal [3, 4], bac-
tericidal [5, 6], anesthetic [7], and antiviral [8] ac-
tivity; but the most noted applications of these
compounds are their use as commercial pesticides
and particularly as herbicides [2, 9], such as ortho-
bencarb and benthiocarb [10–13] for the control of
various noxious weeds.
S-Alkyl thiocarbamates have previously been pre-
pared by reaction of carbamoyl chlorides with thiols
in the presence of pyridine [14] or with alkali thio-
lates[15], or by reaction of alkyl chlorothioformate
(RSCOCl) with amines [16]. They have also been pre-
pared by acid catalyzed reaction of alcohols with
ꢀ
Corresponding author. E-mail: bmovass1178@yahoo.com

138
B. Movassagh et al.
Condensation of thiols with isocyanates under vari-
ous catalytic (acidic or basic) conditions and solvents
have been reported [26]. However, several disadvan-
tages, such as long reaction times [26b, d, e], use of
halogenated or harmful solvents [26a, b, e, f], low or
high temperatures [26a, d, f], use of costly catalysts
[26b, c], low to moderate yields [26b–d], etc. en-
countered in the reported methodologies necessitate
the development of a more efficient and convenient
method.
In practice, from an ecological point of view, the
best solvent is without a doubt no solvent. There are
of course many reactions that can already be carried
out in the absence of solvent. Reports on solvent-
free reactions have, however, become increasingly
frequent and specialized over the past few years.
Areas of growth include reactions between solids
[27], between gases and solids [28], and on sup-
ported inorganic reagents [29], which in many cases
are accelerated or even made possible through mi-
crowave irradiation [30]. There are also reactions
in which at least one reactand is liquid under the
conditions employed, which means that the sol-
vent that would normally be used can simply be
left out.
Results and Discussion
In continuation of our interest on solvent-free re-
actions [31], we wish to report herein a mild, clean,
simple, and highly efficient uncatalyzed method for
preparation of thiocarbamates from isocyanates and
thiols under neat and solution conditions (Scheme 1).
The experimental procedure for the reaction is
very simple: an equimolar amount of isocyanate was
added to liquid or molten thiol at 25–70ꢁC and was
stirred at that temperature for 1–300 min as required
to complete the reaction (monitored through TLC).
The reaction was directly subjected to preparative
TLC to furnish the pure product.
A series of aromatic thiols (containing electron-
withdrawing and electron-releasing groups) as well
as aliphatic thiols and different isocyanates were
used (Table 1). The structures of all the products
were established from their physical and spectral
1
(IR, H, and 13C NMR) properties. The reaction of
aromatic thiols and different isocyanates are in gen-
Although there are several examples for synthesis
of thiocarbamates from isocyanates and thiols, to
the best of our knowledege no study has been made
under solvent- and catalyst-free conditions with a
view to developing a practical methodology.
Scheme 1
Table 1. Synthesis of S-aryl (alkyl) thiocarbamates under catalyst-free conditions
b
Entry
R1
R2
Product
Solvent-freea
CH2Cl2
t=ꢁC
Time=min (yieldc=%)d
Time=min (yieldc=%)
1
2
3
4
5
6
7
8
9
Ph
4-ClC6H4
4-CH3C6H4
4-BrC6H4
n-C8H17
n-C6H13
Ph
cyhex
cyhex
cyhex
cyhex
cyhex
cyhex
Et
n-Bu
Ph
Ph
Ph
PhSCONHcyhex
4-ClC6H4SCONHcyhex
4-CH3C6H4SCONHcyhex
4-BrC6H4SCONHcyhex
n-C8H17SCONHcyhex
n-C6H13SCONHcyhex
PhSCONHEt
PhSCONHn-Bu
PhSCONHPh
4-CH3C6H4SCONHPh
4-ClC6H4SCONHPh
4-BrC6H4SCONHPh
25
55
45
70
25
25
25
25
45
45
55
70
1 (92) [17]
8 (89) [17]
4 (92) [17]
40 (98)
15 (81)
50 (96)
15 (91)
300 (75)
270 (71)
90 (91)
90 (86)
60 (74)
80 (81)
60 (88)
60 (80)
6.5 (86) [16]
300 (82) [17]
270 (85) [17]
90 (96) [32]
90 (91) [32]
35 (91) [25]
50 (93) [25]
30 (72) [25]
32 (80) [25]
Ph
Ph
10
11
12
4-CH3C6H4
4-ClC6H4
4-BrC6H4
Ph
a
All reaction were carried out using equimolar amounts of thiols and isocyanates without a solvent at 25–70ꢁC
b
c
d
All reaction were carried out using equimolar amounts of thiols and isocyanates (1 mmol) in 0.3 cm3 CH2Cl2 at 25ꢁC
Isolated yield
References for known compounds

Synthesis of Thiocarbamates
139
whole mixture was stirred at 45ꢁC (oil bath) for 4 min as
indicated by TLC for a complete reaction. The reaction mix-
ture was then allowed to cool at room temperature, followed
by preparative TLC of the crude product over silica gel plate
(EtOAc:n-hexane¼ 1:4) to afford 229 mg of the pure thiocar-
bamate (92%) as colorless crystals, mp 125–126ꢁC (Ref. [17]
mp 125ꢁC).
eral fast (1–90 min) and clean, and thiocarbamates
are obtained as the sole product in high to excellent
yields. In the cases of aliphatic thiols (entries 5 and
6, Table 1) longer reaction times are required. In
some cases, higher (>25ꢁC) temperatures were need-
ed to dissolve the solid thiols. The treatment of aro-
matic thiols with aliphatic (cyclohexyl) isocyanate
(entries 1–4, Table 1) are much faster than those
with aromatic (phenyl) isocyanate (entries 9–12,
Table 1); this is due to the lower reactivity of phenyl
isocyanate toward nucleophiles (thiols) compared
to cyclohexyl isocyanate. The treatment of aromatic
thiols containing an electron-releasing group, e.g.,
4-methylthiophenol, with isocyanates (entries 3 and
10, Table 1) gave higher yields than those bearing an
electron-withdrawing group.
Typical Procedure Exemplified by the Preparation
of S-4-Methylphenyl N-cyclohexylthiocarbamate
in Dichloromethane
To 124 mg 4-methylthiophenol (1.0mmol) dissolved in 0.3 cm3
CH2Cl2 was added 125 mg cyclohexylisocyanate (1.0 mmol),
and the mixture was stirred for 50min at 25ꢁC. After comple-
tion of the reaction (monitored by TLC), the solvent was
evaporated in vacuo and the crude product was purified by
preparative TLC (silica gel, eluent EtOAc:n-hexane¼ 1:4) to
obtain 239 mg (96%) of the pure thiocarbamate.
In order to compare the results with those obtained
in solution, we studied the above reaction in a mini-
mum amount (0.3 cm3 per 1 mmol of substrate) of
dichloromethane (CH2Cl2). As shown in the Table,
there are appreciable differences, both in reaction
times and=or isolated yields, between the results ob-
tained in solution and those in neat conditions. Thus,
by omitting the solvent, in addition to the ease of the
work-up procedures, the reaction time was significant-
ly reduced and thus, the need for solvent is avoided.
In conclusion, the present catalyst- and solvent-free
procedure provides a powerful and versatile method
for the preparation of S-aryl (alkyl) thiocarbamates.
This method is endowed with several unique merits,
namely, simplicity in operation, mild reaction condi-
tions, avoiding hazardous organic solvents, toxic and
expensive reagents, short reaction times, and high
product yields. This environmentally benign process
represents a suitable option to existing methods.
Acknowledgments
We are pleased to acknowledge the financial support from the
K.N. Toosi University of Technology Research Council and
Kermanshah Oil Refining Company.
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