profound effect on biological systems. Dithiocarbamates are
also widely used in medicinal chemistry and have found appli-
cation in the treatment of cancer.7 Furthermore, dithiocar-
bamates are versatile classes of ligands with the ability to
stabilize transition metals in a wide range of oxidation states.8
Dithiocarbamates have a wide range of uses and applica-
tions and are produced in great quantities throughout the
world. Therefore, the synthesis of this type of molecule has
received considerable attention. General methods for their
synthesis involve the reaction of an amine with costly and
toxic reagents, such as thiophosgene and/or an isothiocyan-
ate.9 Furthermore, a one-pot reaction of amines with carbonyl
sulfide and alkyl halides in organic solvent in the presence
of a catalyst also has been developed.10 However, there are
several disadvantages to these methods: many isothiocyan-
ates are hazardous and tedious to prepare and display poor
long-term stability with the formation of side products such
as urethane in alcoholic media. Such intermediates also
require high reaction temperatures, give low or moderate
yields of products, and usually entail multistep procedures.
Furthermore, these reactions require very toxic reagents and
harmful organic solvents such as DMF and DMSO in the
presence of a catalyst.
During the course of a study aimed at improving the eco-
compatibility of certain organic processes, we evaluated the
possibility of performing these organic transformations under
solvent-free conditions,11 so as to develop environmentally
benign reactions.12 Herein, we now describe an efficient,
novel, and highly simple procedure for the direct synthesis
of thiocarbamates from the one-pot reaction of amines, CS2,
and alkyl halides, without the use of any catalyst and under
solvent-free conditions at room temperature (Scheme 1).
The starting point for our experiments was to optimize
the reaction conditions for the large-scale industrial produc-
tion of S-alkyl dithiocarbamates which are used as herbicides,
insecticides, and fungicides and produced in large quantities
around the world. Thus, after surveying different reaction
conditions, it was found that upon simple mixing of
diethylamine (6 mmol), CS2 (6 mmol), and benzyl chloride
Scheme 1. One-Pot Synthesis of S-Alkyl Dithiocarbamates
(3 mmol) quantitative conversion to S-alkyl dithiocarbamate
7 was observed with excellent yields. The reaction was also
carried out in organic solvents, such as ClCH2CH2Cl, THF,
diethyl ether, CH3CN, and ethanol, for comparison. As shown
in Scheme 2, good yields of product were also formed in
Scheme 2. Screening of Solventsa
a Reaction conditions: solvent (4 mL), amine (6 mmol), CS2 (6
mmol), and benzyl chloride (3 mmol).
organic solvents such as CH3CN and THF after 5 h.
However, we observed that under solvent-free conditions at
room temperature the one-pot reaction proceeded to comple-
tion, affording the S-alkyl thiocarbamate in excellent yield
without the use of any catalyst.
Next, the scope and limitation of this simple process were
explored by using a wide range of alkyl halides and amines.
A variety of structurally diverse amines and alkyl halides,
including chloride, bromide, and iodide, underwent the one-
pot reaction smoothly without using any catalyst or solvent to
afford the corresponding S-alkyl dithiocarbamate derivatives
in good to high yields. The results are summarized in Table 1.
The generality of the present method was also extended
to amine components. Primary, allylic, benzylic, hindered,
and unhindered secondary and tertiary alkyl primary amines
were used in this protocol with excellent results. However,
aromatic amines did not participate in the reaction. The
reactions were completed after 3-12 h affording 68-97%
yields. Commercially available alkyl halides and amines were
used under the same reaction conditions for both reactive
and unreactive alkyl halides and amines. Thus, a diverse set
of synthetically useful dithiocarbamate products can poten-
tially be prepared in one step by this method.
Generally, the solvent-free reaction is experimentally
simple, proceeds well without any catalyst, and generates
virtually no byproducts. Equally important is the wide scope,
high selectivity, and nearly quantitative yields of this
transformation, which collectively allow significant structural
diversity to be incorporated into the products, many of which
could not be obtained via the older procedures. Furthermore,
all the reactions performed here involved stirred homoge-
neous liquids. As the reaction proceeds, the mixture solidifies
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