Microwave-assisted ring opening of epoxides with thiols on montmorillonite K-10 solid support

Solvent-free ring opening of 1,2-epoxides with aromatic thiols under microwave irradiation in the presence of montmorillonite K-10 clay affords high yields of β -hydroxy sulfides. Nucleo-philic attack of the thiols occurs regioselectively at the less hindered side of the epoxides


Introduction
Ring opening of epoxides with thiols is an important method of organic transformation and has found much use in pharmaceutical 1 and natural product chemistry, 2 particularly for the synthesis of leukotrienes. 3The classical approach for the synthesis of β-hydroxy sulfides involves nucleophilic ring opening of epoxides with thiols in the presence of species such as InCl 3 , 4 ZnCl 2 , 5 B(C 6 F 5 ) 3 , 6 ceric ammonium nitrate, 7 hexafluoroisopropyl alcohol, 8 lithium bistrifluoromethanesulfonimide, 9 CoCl 2 , 10 alumina, 11 polyethylene glycol, 12 gallium complexes, 13 NiCl 2 •6H 2 O, 14 CsF on celite, 15 lanthanide complexes, 16 and lithium perchlorate. 17In many of these cases, the ring opening of epoxides is carried out in a halogenated solvent normally requiring long time treatment under refluxing temperatures or environmentally unfriendly conditions.
Stringent environmental protection laws in recent years prompted an increasing emphasis on the use and design of eco-friendly reagents, solid state procedures, and solvent-free reactions. 18pplication of microwave techniques is currently under extensive examination, 19 and dry procedures have recently attracted much attention because they can be carried out in open vessels, and the use of expensive and hazardous organic solvents can be avoided. 20We extended our previous experience on solid supported microwave-promoted ring opening of epoxides with amines. 21Here, we report a simple fast procedure for efficient thiolysis of epoxides on an inexpensive and convenient heterogeneous catalyst surface under solvent-free conditions.Initially, 2-(phenoxymethyl)oxirane 1a was treated with an equimolar amount of thiophenol 2a in the presence of montmorillonite K-10 clay under microwave irradiation and without any solvent.The experiments were complete within 75 seconds as monitored by TLC showing the disappearance of the starting epoxide 1a.The 1 H NMR spectrum of the crude reaction mixture revealed the formation of the β-hydroxy sulfide 3aa indicating that the nucleophilic attack of the thiol occurred at the less hindered side of the epoxide (Scheme 1).Moreover, in the crude mixture the opposite regioisomer was detected in a very small amount (~5%) proving the high regioselectivity of the reaction.Bulb to bulb distillation of the crude mixture gave 92% of the desired product 3aa (Table 1, entry 1).Control experiments confirmed the combined promoting effect of the solid support and microwave irradiation.When a mixture of thiophenol 2a and 1a was irradiated in a microwave oven without the solid support for more than 5 minutes, no product was detected.An alternative reaction without microwave irradiation led to formation of only 20% of 3aa after several hours.Epoxide 1a reacted in a similar manner with pchlorothiophenol 2b and 2-thionaphthol 2c producing of 3ab and 3ac in 85% and 77% yield, respectively (entries 2, 3).The generality of the method was illustrated by subjecting epoxides 1b-d to the reaction with thiols 2a-c on the same solid support (entries 4-12).Consequently, products 3ba-3dc were obtained in 78-87% yields in less than 2 minutes microwave irradiation.3aa−3dc (see Table 1) Microwave promoted thiolysis of epoxides 1 on monmorillonite support.

Conclusions
In summary, the microwave-promoted ring opening of epoxides with thiols was carried out in less than 2 minutes under solvent-free conditions in the presence of montmorillonite K-10 clay.The environmental safety of the process, high yields of the products, good regioselectivity of the ring opening, and rapid completion of the reactions are among the advantages of this method, which makes it an attractive addition to the existing literature.

Experimental Section
General Procedures.A conventional microwave oven (900 W) was used for the irradiation of the reaction mixtures.All reported yields are isolated yields.Melting points were determined with a Buchi melting point apparatus and are corrected.TLC experiments were carried out on silica gel plates with UV indicator from Aldrich; visualization was by UV fluorescence or by staining with iodine vapor.IR spectra were recorded on a Bruker Vector 22 FT-IR spectrophotometer using KBr disks or as neat samples. 1 H NMR spectra were recorded on FT-NMR Bruker Ultra Shield TM (500 MHz) or Bruker AC (80 MHz) instruments with CDCl 3 as solvent and TMS as internal reference.GC-MS spectra were obtained on a Fisons 8000 Trio instrument at ionization potential of 70 eV.Elemental analyses were performed using a Heraeus CHN-O-Rapid instrument.All chemicals were available from Aldrich and used as purchased.
β-Hydroxysulfides 3 and 5. General procedure A mixture of epoxide (1 or 4; 5.0 mmol), aromatic thiol 2 (5.0 mmol) and montmorillonite K-10 clay (1.0 g) was placed in a beaker (50 mL), and the mixture was irradiated at high power in a conventional microwave oven for an appropriate length of time (Table 1).The course of the reaction was monitored by TLC until complete disappearance of the starting material was observed.The mixtures were cooled to room temperature, dissolved in dichloromethane (10 mL), and filtered through a celite column.The solvent was removed at reduced pressure and the respective product 3 or 5 was purified by column chromatography over silica gel or by bulb to bulb distillation.The 1 H NMR, IR, and GC-MS spectra of the products were obtained and compared with those reported in the literature.