A new one-pot synthesis of thiocarbamates from isocyanates and disulfides in the presence of Zn/AlCl3 system

Article abstract of DOI:10.1246/cl.2005.1330

A novel method has been developed for the synthesis of S-alkyl(aryl) thiocarbamates. The route involves, first, the formation of zinc thiolates by reductive cleavage of disulfides in the presence of Zn/AlCl₃ system; then subsequent reaction of

Full text of DOI:10.1246/cl.2005.1330

1330
Chemistry Letters Vol.34, No.10 (2005)
A New One-pot Synthesis of Thiocarbamates from Isocyanates
and Disulfides in the Presence of Zn/AlCl3 System
Barahman Movassaghꢀy;yy and Yousef Zakinezhady
yDepartment of Chemistry, K. N. Toosi University of Technology, P. O. Box 16315-1618, Tehran, Iran
yyKermanshah Oil Refining Company, Kermanshah, Iran
(Received June 9, 2005; CL-050748)
A novel method has been developed for the synthesis of
S-alkyl(aryl) thiocarbamates. The route involves, first, the
formation of zinc thiolates by reductive cleavage of disulfides
in the presence of Zn/AlCl3 system; then subsequent reaction
of the thiolate anions with isocyanates gives the desired thiocar-
bamates in high to excellent yields.
O
C
H
Zn/AlCl3
R1SSR1 + R2
N
C
O
R1S
N
CH3CN/H2O, 65 °C
R2
1
2
3
Scheme 1.
Thiocarbamates, especially S-alkyl thiocarbamates, are an
important class of compounds that have numerous biological ef-
fects ranging from fungicidal,1,2 pesticidal,3,4 anesthetic,5 bacter-
icidal,6,7 and antiviral8 activity; but, the most noted application
of these compounds is their use as commercial herbicides4,9 such
as benthiocarb and orthobencarb.10–13
H2O mixed solvent at 65 ꢁC (Scheme 1).
A series of symmetrical alkyl and aryl disulfides treated with
various isocyanates in the presence of Zn/AlCl3 system with
a molar ratio of disulfide:AlCl3:isocyanate = 0.5:1:1.5. The
disappearance of zinc powder during the preliminary treatment
of disulfides with Zn/AlCl3 is attributed to the formation of zinc
thiolate intermediate25 which further undergoes nucleophilic
attack to the isocyanate to afford the thiocarbamate in high to
excellent yields.26
The results are summarized in Table 1. Reactions are very
clean and thiocarbamates are obtained as a sole product during
short times in high to excellent yields. The work-up of the reac-
tion is accomplished by simple filtration and evaporation of the
organic solvent (CH3CN), and finally purification is involved.
In conclusion, this method is attractive since it offers some
advantages over earlier reported protocols in that it avoids multi-
step procedures, and preparation of complex starting materials.
Mild condition, short reaction time, and high isolated yields of
the products are other advantages of this method.
Classical methods for preparation of S-alkyl thiocarbamates
illustrate the intramolecular rearrangement of various deriva-
tives;14 however, these rearrangements are extremely dependent
upon starting substrates and the reaction conditions. They have
also been prepared by acid catalysed hydration of alkyl and aryl
thiocyanates; but, this method is limited to only N,N-unsubstitut-
ed thiocarbamates.15 Several other methods have been reported
for the preparation of this thiocarbamates; however, most require
the preparation of complex starting materials and multistep ap-
proaches, among them: the reaction of alkyl chlorothioformate
(RSCOCl, prepared from thiols and phosgene) with amines,16
reaction of amines and thiols in the presence of carbon monoxide
under (PPh3)2NiBr2 and (PPh3)2NiCl2 catalysts,17 DBU-assisted
carbonylation of amines with carbon monoxide and sulfur,18
carbamoylation of thiols using carbamoyl imidazolium salts,19
reaction of elemental sulfur with carbon monoxide and alkyl
amines in the presence of a catalytic amount of selenium and
subsequent addition of primary alkyl halides.20 Condensation
of thiols with isocyanates give the corresponding thiocarba-
mates.21 Other groups4,10 have prepared these compounds from
condensation of gaseous carbonyl sulfide (COS) with a secon-
dary amine in the presence of a base. N,N-Disubstituted S-alkyl
thiocarbamates have also been prepared from salts of dithiocar-
bamic acid, which are prepared by the addition of secondary
amines to carbon disulfide.22 Recently, Wynne and co-workers23
reported two approaches for the synthesis of S-alkyl thiocarba-
mates using trichloroacetyl chloride. Thiocarbamates have also
been prepared from asymmetrical disulfides in two steps;24 in
the first step, disulfides were converted into the corresponding
thiols, and finally the thiols reacted with isocyanates to afford
thiocarbamates in good yields.
Table 1. N-Substituted-S-alkyl (aryl) thiocarbamates 3a–3m
Time
/min
Yield
/%b
Entry
R1
R2
Producta
1
2
3
4
5
6
7
8
9
10
11
12
13
Ph
Ph
Ph
Ph
Ph
Ph
n-C4H9
n-C4H9
40
55
35
30
35
45
45
25
50
40
30
25
25
b
3a27
3b27
3c27
3d18
3e28
3f18
90
88
93
94
92
91
90
92
89
91
93
95
79
p-MeC6H4
p-ClC6H4
CH3
CH3CH2
CH3
CH3CH2
CH3CH2CH2 n-C4H9
n-C6H13
CH3CH2
3g10
3h10
3i23
n-C4H9
CH3CH2
3j28
CH3CH2CH2 CH3CH2
CH3CH2
Ph
3k10
3l16
n-C4H9
HOCH2CH2
3m29
aReferences of the known compounds. Isolated yields.
In connection with our ongoing work on Zn/AlCl3 system,
we now describe a new method for preparation of N-substituted-
S-alkyl(aryl) thiocarbamates 3 which involves treatment of
disulfides 1 and different isocyanates 2 promoted by cheap and
reactive metallic zinc in the presence of AlCl3 in CH3CN–
This study was supported by K. N. Toosi University of
Technology Research Council and Kermanshah Oil Refining
Company.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.10 (2005)
1331
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Published on the web (Advance View) September 3, 2005; DOI 10.1246/cl.2005.1330