A simple catalyst-free, and highly regioselective approach to 2-hydroxyalkyl dithiocarbamates is described which involves a one-pot reaction of various amines and carbon disulfide,CS2, with epoxides in ethanol at room temperature.
The formation of carbon-sulfur bond, especially under a green and safe condition, is an important transformation in organic synthesis. Sulfur containing compounds are found in many products of biological [1-4] and medical [5-7] relevance as well as in commercial drugs [
Dithiocarbamates are a class of fungicides extensively used worldwide on a range of crops mainly due to their efficiency in controlling plant fungal diseases and relatively low mammalian acute toxicity [
In recent years, much attention has been paid to functionalized dithiocarbamates; among them, 2-hydroxy dithiocarbamates represent an important class of key compounds that have been used for various applications, especially as synthetic intermediates [34-36], as multifunctional lubricant additives [37,38], and as electrophotographic liquid developers [39,40]. They are usually synthesized by one of the following main methods: (1) reaction of an amine and carbon disulfide, to form dithiocarbamic acid salt, with epoxides [41,42], or with 2-hydroxyalkyl halides [
One important issue in green chemistry which is currently receiving an increasing attention is the use of alternative reaction media that circumvent the problems associated with many of the traditional toxic and volatile organic solvents. Many issues surrounding a wide range of volatile and non-volatile, polar aprotic solvents have stimulated fine chemical and pharmaceutical industries to seek more benign alternatives [
As part of our research to develop practical, simple, and green methodologies in organic synthesis [46-58], herein we describe an efficient, catalyst-free synthesis of 2-hydroxyalkyl dithiocarbamates from primary or secondary amines and CS2 with epoxides in ethanol (Scheme 1).
In order to optimize the reaction condition with respect to solvent, time, temperature, and molar ratios of the components, the reaction of 2,3-epoxypropyl phenyl ether with benzylamine and carbon disulfide was planned as a model reaction in the absence of any catalyst. It was found that by simple initial mixing of benzylamine (1.2 mmol) and carbon disulfide (1.3 mmol) in ethanol (1.5 mL) at room temperature, followed by addition of the epoxide (1.0 mmol) at that temperature, the expected dithiocarbamates were obtained in 92% yield within a very short time. The reaction was also conducted in water but under the same reaction condition as above; however, it yielded no expected product even after 3.5 hrs.
To explore the generality and scope of this method, various amines (primary, secondary, benzylic and aromatic) and epoxides were examined under the conditions outlined above. As it can be seen from
We assume that the unstable dithiocarbamic acid 5, initially generated from the amine and CS2, reacts with the epoxide 2 giving rise to the formation of the 2-hydroxyalkyl dithiocarbamates 3 and 4 (Scheme 2).
To conclude, we have developed a very convenient and efficient regioselective and catalyst-free protocol for the one-pot reaction of various aliphatic/aromatic amines and CS2 with different epoxides in ethanol at room temperature. In this fast and high yielding method, the use of low temperature is avoided.
Melting points were recorded on a Buchi B-540 apparatus and were uncorrected. IR spectra were recorded on an ABB FTLA 2000 instrument. NMR spectra were recorded with either a Bruker AQS-300 or Bruker DRX-500 spectrometer with nominal frequencies of 300 MHz and 500 MHz for proton or 75 and 125 MHz for carbon, respecttively in CDCl3 using TMS as an internal standard.
A stirred solution of carbon disulfide (1.3 mmol) in EtOH (1.5 ml) was slowly treated with the amine (1.2 mmol); the mixture was stirred for 15 mins at room temperature, followed by addition of the epoxides (1.0 mmol) in one portion; stirring, at room temperature, was continued for the length of time indicated in
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We wish to thank Dr. Sogand Noroozizadeh for editing the manuscript and the K. N. Toosi University of Technology Research Council for financial support of this work.