General Papers ARKIVOC 2008 (xi) 46-55
epoxides for the preparation of ß-hydroxy sulfides in water without using any catalyst has not been attempted before. Very recently opening of epoxides by nucleophiles has been carried out in water under simultaneous ultrasound/microwave irradiation.12 We report herein a practical methodology for the preparation of ß-hydroxy sulfides by thiolysis of epoxides in water without using any catalyst or special technical requirement (Scheme 1).
R1SH
RO SR1
RO
O Water, 70 oC
OH
Scheme 1. Regioselective thiolysis of epoxide in water.
Results and Discussion
In a set of initial experiments, a mixture of fructose derived terminal epoxide (Table 1, entry 2) and a varied quantity of thiophenol in water was allowed to stir at different temperatures ranging from room temperature to 80 °C. It was observed that use of 2.5 equiv. of thiol and water (3 mL/mmol of substrate) under vigorous stirring at 70 °C furnished a clean formation of ß-hydroxy sulfide derivatives in excellent yield in 5 h. Following similar reaction condition a series of ßhydroxy sulfide derivatives have been prepared using different thiols in excellent yield (Table 1). In general, all reactions are very clean and high yielding. Variation of the quantity of water used did not show any significant change in the reaction rate. However, stirring plays an important role on the reaction time. In a comparative study, only ~40% conversion took place by keeping a mixture of epoxide and thiol in water at 70 °C without stirring even after 24 h. The reaction does not require any organic solvent as co-solvent. Carrying out the reaction without using water in a neat reaction condition did not give satisfactory yield of the product. All products were characterized by NMR and mass spectral analysis. Most of the reactions are highly regioselective except in the case of styrene epoxide (Table 1, entry 8) in which a mixture of both regioisomers were obtained due to the addition of thiols to the benzylic carbon to give the major product. It is presumed that water forms hydrogen bonding with the oxygen atom of the epoxide ring as well as with the thiol making them closely associated, which enhances the attack of thiol to the epoxide towards the formation of ß-hydroxy sulfides. In another approach, it can be explained by considering the acidic thiol acts as its own Lewis acid, which forms an ion pair of a protonated epoxide and a thiolate and thus enhances the ring opening. Although the aromatic thiols furnished excellent yield of the ß-hydroxy sulfides, aliphatic thiols did not give satisfactory results may be due to their less acidic nature. In the case of aliphatic thiols, no ring opened product of the epoxide was observed after a longer reaction time. To further prove the efficacy of the present protocol, a comparison study has been carried out to the previously reported methods for thiolysis of epoxides using water as reaction medium, which are presented in Table 2. From
ISSN 1551-7012 Page 47 ©ARKAT USA, Inc.
