An efficient one-pot approach to the synthesis of symmetric trithiocarbonates from carbon disulfide and alkyl halides using imidazole

A novel method is reported for the synthesis of symmetric dialkyl and cyclic (5, 6 and 7 member) trithiocarbonates from alkyl halides and carbon disulfide in the presence of imidazole and water in DMSO under mild reaction conditions. Imidazole is used as an inexpensive, non-toxic and readily available catalyst in this procedure. GRAPHICAL ABSTRACT


Introduction
Dialkyl trithiocarbonates are of importance in synthetic chemistry, biochemistry and industry. [1][2][3][4][5] They are especially used as pesticides in agriculture, [6,7] lubricating additive, [8,9] reversible addition fragmentation chain transfer agent in the free radical polymerization reactions, [10,11] pharmaceuticals, [12,13] agrochemical [14,15] and intermediate in organic synthesis. [16][17][18][19][20] The most convenient method for the synthesis of symmetrical trithiocarbonates is alkylation (arylation) of CS 2− 3 with alkyl (aryl) halides. The trithiocarbonate anion [21,22] is generally prepared by in situ one-pot reaction of carbon disulfide with alkali metal or ammonium sulfide, [23][24][25] ammonium hydroxide, [21] KF/alumina or alumina, [26,27] anion-exchange resin [28] and hydroxide, [29,30] carbonate [29] and the phosphate [31] of the alkali metal group. In our previous studies, we used KF/Al 2 O 3 [26] as a recyclable catalyst and tetra-n-butyl ammonium hydroxide [32] as a neat aqueous medium for the one-pot synthesis of symmetrical dialkyl trithiocarbonate. This was an effective method and suitable from the novelty and green chemistry view points; [33] but like all other reported methods, the catalysts were inorganic. The use of inorganic and metal bases has several disadvantages such as their expense, their toxic and corrosive behavior, the strongly basic reaction conditions that are employed, and the difficulty in work-up encounter in these reactions. Herein, we describe a new alternative approach to one-pot synthesis of symmetrical dialkyl trithiocarbonate from carbon disulfide and alkyl halides using imidazole as a highly stable, readily available, low-cost, low toxicity and mild organic compound.

Results and discussion
As a model, the reaction of benzyl chloride (2.0 mmol) 1 and carbon disulfide (6.0 mmol) 2 in the presence of imidazole (6.0 mmol) was studied under normal atmospheric conditions in order to optimize the reaction conditions with respect to the solvent and temperature (Scheme 1). Several solvents were examined at room temperature and at 45 • C. According to the results given in Table 1, it was found that the reaction solvent and temperature significantly affected the rate of reaction and the type and amount of product formed. In aqueous DMSO and DMF, product 3 was the main product, whereas by-product 4 was the major product in the absence of water (0.2 ml). The presence of water is often beneficial to the rate and selectivity of the reaction. Furthermore, the yield and rate of reaction also increased with temperature, whereas the formation of by-product 4 was reduced. In aqueous DMSO and DMF at 45 • C, dibenzyl trithiocarbonate 3 was obtained as the sole product, while at room temperature 15-23% of byproduct 4 was also isolated. Despite the fact that DMF and DMSO promoted the reaction, no reaction was observed in THF or 1,4-dioxane. Furthermore, during our optimization studies we discovered that decreasing the imidazole from 6 to 4 or 5 mmol decreased the efficiency of the reaction and lowered the yields to 53% and 78%, respectively.
Eventually, a large number of symmetrical dialkyl trithiocarbonate 6a-6m were synthesized under the optimized conditions by the reaction of alkyl halides 5 with carbon disulfide in the presence of imidazole at 45 • C under normal atmospheric conditions (Scheme 2, Table 2).
The procedure worked well with primary, secondary, and tertiary alkyl, benzyl and alkyl halides, to give the corresponding dialkyl trithiocarbonates as the sole product in high to excellent yields (Table 2). However, the attempted reactions of aryl halides failed under the same conditions, even after long reaction times (Table 2, Entry 13). More interestingly, the base-sensitive functional groups such as carboxylic ester and carboxylic acid remained unchanged in the synthesis of corresponding symmetric trithiocarbonates (6j and 6k) from α-bromoethyl acetate 5j and α-chloroacetic acid 5k (Table 2, Entries 10, 11).

5(a-m) 6 (a-m)
Scheme 2. Synthesis of symmetric trithiocarbonates. Furthermore, the procedure's efficiency for the synthesis of cyclic trithiocarbonates (1, 3dithiolane-2-thione) from dihalides 7 was examined (Scheme 3). Five-(8a), six-(8b) and sevenmembered cyclic trithiocarbonates (8c) were successfully prepared with moderate yields without any by-product (Table 3).  In order to establish the general applicability of the procedure for the synthesis of unsymmetrical dialkyl trithiocarbonate from two different alkyl halides under optimal reaction conditions, αbromo ethyl acetate 5j and ethyl iodide 5a were treated with carbon disulfide and imidazole (Scheme 4). The unsymmetrical trithiocarbonate product 9 was obtained as the major product (60%) with good chemoselectivity. The symmetrical products 10 (25%) and 11 (10%) were isolated as the minor products.  Scheme 5. A Proposed mechanism for the trithiocarbonylation of alkyl halides in the presence of imidazole.

Conclusion
To conclude, this strategy provides a new and alternative procedure for the one-pot synthesis of symmetrical dialkyl trithiocarbonates from alkyl halides and carbon disulfide. It is more economic, more general and more environmentally friendly than previous methods. The use of imidazole as an inexpensive, non-toxic and readily available catalyst is another significant advantage of this process. In addition, other advantages of this process are the ease of performing and controlling the reaction as well as purification of the product, and the avoidance of expensive and/or dangerous reagents.

Experimental
General procedures: Symmetrical trithiocarbonates synthesis from alkyl halides and carbon disulfide: Alkyl halides (2.0 mmol) (or alkyl dihalides (1.0 mmol)) were added in one portion to a solution of imidazole (6.0 mmol) and CS 2 (6.0 mmol) in 5 ml DMSO/H 2 O (4.8/0.2). The color of the resulting reaction solution immediately changed from light red to yellow. Then, the solution was allowed to stir for the appropriate time (Table 2) at 45 • C in an air atmosphere. The progress of the reaction was monitored by TLC. After completion of the reaction, 20 ml CH 2 Cl 2 was added to the mixture, and the mixture was then washed with water (2 × 20 ml). The organic layer was separated and then dried over anhydrous Na 2 SO 4 . The solvent was evaporated under reduced pressure. The residue was purified by preparative TLC silica gel, eluent n-hexane: EtOAc; 30:1) to afford pure product (symmetric dialkyl trithiocarbonate). In the case of Entries 10 and 11, Table 2 (6j and 6k), the TLC eluent was n-hexane: EtOAc 4:1.
Selected spectral data for representative trithiocarbonate:

Funding
Financial support from Ilam university research council is gratefully acknowledged.

Supplemental data
Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/17415993.2014.919296.