Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers

Silica: An efficient catalyst for one-pot regioselective synthesis of dithioethers Samir Kundu, Babli Roy and Basudeb Basu* Full Research Paper Address: Department of Chemistry, North Bengal University, Darjeeling 734013, India, Fax: +91 353 2699001 Open Access Beilstein J. Org. Chem. 2014, 10, 26–33. doi:10.3762/bjoc.10.5 Email: Basudeb Basu* - Received: 15 September 2013 Accepted: 11 November 2013 Published: 07 January 2014 * Corresponding author Associate Editor: B. Stoltz Keywords: allyl halide; dithioether; silica gel; tandem reactions; thiol © 2014 Kundu et al; licensee Beilstein-Institut. License and terms: see end of document. Abstract The development of a silica-promoted highly selective synthesis of 1,2 or 1,3-dithioethers via solvent-free one-pot tandem reactions of an allyl bromide with excess thiol at room temperature is described. The choice of silica gel, either pre-calcined or moistened with water, exhibited notable regioselectivity in the formation of dithioethers. Plausible mechanistic routes were explored and postulated. Introduction Organosulfur compounds are important building blocks for the synthesis of various biologically active molecules [1-3]. Versatile applications of organosulfur compounds are known in fields such as the pharmaceutical, the polymer, the pesticide and the food-processing industry [4-8]. For example, organosulfur compounds in garlic are often used in food-processing industries as flavouring and preservative agents and are also used as herbal medicine [4]. Dithioethers are commonly employed as ligands in preparing metal-coordination complexes and also as spacers in metal-organic frameworks [9-14]. For example, vicinal dithioether-based zirconium and titanium complexes have been used for alkene polymerization and hydroamination [15-18]. Chiral dithioethers have been prepared and their iridium complexes have been employed in asymmetric hydrogenation [18]. Vicinal dithioethers are generally synthesised either by the metal-catalyzed addition of disulfides to alkenes [19,20] or by the traditional nucleophilic substitution of 1,2-dihalides with suitable thiols/thiolates [21,22]. They are also prepared by consecutive hydrothiolation of alkynes, both under nucleophilic and radical-induced conditions [22,23]. On the other hand, 1,3dithioethers can be prepared by the nucleophilic substitution of compounds bearing suitable leaving groups at 1,3-positions of alkyl chains [21]. Because of their versatile applications, a great number of procedures have been developed to synthesize bis(thioethers) with varying degrees of success and a variety of limitations [19-31]. Over the last decade, organic synthesis has taken a major turn towards developing reaction conditions that are environmentally friendly and sustainable [32-36]. Mesoporous inorganic 26 Beilstein J. Org. Chem. 2014, 10, 26–33. oxides, which often facilitate various organic reactions, are considered suitable to promote eco-friendly chemical processes [36]. Organic reactions with a high selectivity under ecofriendly and sustainable conditions are attractive features in terms of the concepts of Green chemistry. Previously, we have developed silica-promoted facile and highly selective methods for N and S-alkylations/acylation from amines or thiols, respectively [37,38]. An equimolar mixture of a benzenethiol and allyl bromide on treatment with silica afforded allyl(phenyl)sulfane in excellent yield. Since alkenes are also known to undergo ‘click’ addition with thiols [39,40], excess use of thiols could effectively produce dithioethers, and based on a regioselective addition one could achieve either vicinal or 1,3-dithioethers in one-pot consecutive substitution–hydrothiolation processes (Scheme 1). Although both reactions are wellknown, a search in the literature surprisingly revealed no general one-pot protocols for the preparation of dithioethers from allylic substrates. Recently, Banerjee and co-workers reported on the simple synthesis of thioethers by silica NPs, where a single example of a reaction of an allyl bromide and excess benzenethiol was studied [41,42]. The reaction was carried out in the presence of silica NPs and water, and they isolated 1,3-dithioether by an anti-Markovnikov addition. However, there is no report on the metal-free hydrothiolation of allylic substrates in a Markovnikov fashion to afford 1,2dithioethers in one-pot reactions. In this paper, we wish to report our investigations on the reaction of allyl halides with excess thiols promoted by silica gel, which finally constitutes distinct protocols for one-pot, solvent-free substitution and regioselective additions to produce either 1,2 or 1,3dithioethers. Results and Discussion Following our previous experience [37,38], we first attempted the magnetic stirring of a mixture of allyl bromide and benzenethiol in a 1:2.5 ratio by using pre-calcined silica gel at room temperature that indeed led to the formation of 1,2dithioether in 91% yield. On the other hand, if silica gel moistened with a few drops of water was used for the same reaction, the regioselective anti-Markovnikov addition product, i.e., 1,3dithioether, (1-(3-(phenylthio)propylthio)benzene) was obtained in 83% yield. In both cases, a minimal amount of diphenyldisul- fide (5–10%) was formed [43,44], which was easily separable from the reaction mixture by column chromatography. Since the choice of silica led to the production of highly regioselective products, we wanted to optimize both conditions to establish them as general protocols. Table 1 shows the optimization of the reactions of different allylic substrates with benzenethiol. Silica gel (directly from the container, commercially available) was used either pre-activated by heating at 100 °C under vacuum for 1 h and then cooled under vacuum for use under conditions A or moist with water (0.1 mL water for 0.5 g of silica) for use under conditions B. It was observed that allyl bromide or allyl iodide underwent sequential substitution–addition reactions entirely regioselectively with comparable yields (Table 1, entries 1–5), whereas allyl chloride showed varying results under conditions A or B, and allyl acetate did not undergo any desired reaction, but merely produced the disulfide from oxidative dimerization of the thiol (Table 1, entries 6–8). Allyl tosylate, however, produced the desired thioethers in a regioselective manner, but with relatively low yields (Table 1, entries 9 and 10). Interestingly, allylphenylsulfane or allyl phenyl ether entirely followed an anti-Markovnikov addition, under both conditions, A and B (Table 1, entries 11–14). With the two distinct conditions, we examined the scope of these one-pot tandem reactions of allyl bromide with a variety of thiols under both conditions. The results are presented in Table 2. Arylthiols bearing different functional groups like CH3, OCH3, Cl or F were reacted with allyl bromide in the presence of pre-calcined and dry sil (...truncated)