Comparative Study of Microwave Induced and Conventional Synthesis of Acetylated Sugar Isothiocyanates and Related Thiocarbamides

The synthesis of several acetylated sugar isothiocyanates have been carried out under microwave irradiation in excellent yields of products by using related bromides and lead thiocyanate in sodium dried xylene. Several acetylated sugar thiocarbamides have been synthesized by the interaction of respective acetylated sugar isothiocyanates with appropriate aryl amines under microwave irradiation.


Introduction
Owing to present environmental awareness, attempts are being made towards the evolution of environmentally benign processes using microwave induced organic reaction enhancement (MORE).The chief features of microwave assisted reactions are the enhanced selectivity, much improved reaction rates, milder reaction conditions and formation of cleaner products.Microwave irradiation method replaces the classical one because it proves to be a clean, cheap and convenient method 1 .Microwave assisted synthesis affords higher yields and minor wastes.Conventional method required longer heating time, tedious procedure and the excessive use of solvents while microwave assisted reactions are often performed neat, simplifying the work-up process and minimizing the need for organic solvents.Hence, microwave method has emerged as a tool towards green chemistry.Few researchers synthesized aryl thiocarbamides 2 under microwave irradiation.At the present time, microwave assisted carbohydrate chemistry is experiencing considerable growth and has potential to greatly improve the image of carbohydrate chemistry.
Sugar isothiocyanates are the versatile reagent in the field of carbohydrate chemistry.Due to synthetic flexibility of the isothiocyanate function 3 , glycosyl isothiocyanates are attracting much attention among the N-glycosides.Sugar isothiocyanates have been used for the synthesis of carbohydrate derivatives particularly having thiourea structure, of synthetic, biological and pharmaceutical interest [4][5][6] .Antiviral, antibacterial and antitumor agents have been prepared by reaction of glycosyl isothiocyanates with biologically active amines 7,8 .
Conventionally, in our laboratory, a number of researchers [9][10][11] reported the synthesis of acetylated sugar isothiocyanates and related thiocarbamides.We herein report the synthesis of acetylated sugar (glucose, galactose, lactose and maltose) isothiocyanates and related thiocarbamides under microwave irradiation.In the course of our study on carbohydrate chemistry, we found that microwave irradiation could promote the acetylated sugar isothiocyanates and related thiocarbamides in moderate yields.

Experimental
All reactions were carried out in a commercially available Godrej GMC 25E 09 MRGX microwave oven having a maximum power output of 900W operating at 2450 MHz.Melting points were recorded on a MAC digital melting point apparatus and are uncorrected.Thin layer chromatography was conducted on E. Merck TLC Silica gel 60 aluminium sheet.

Results and Discussion
Under microwave irradiation, acetylations of sugars (glucose, galactose, lactose and maltose) have been carried out by using appropriate amount of acetic anhydride and anhydrous sodium acetate as a catalyst.Bromination of acetylated sugars has been carried out conventionally using bromine in acetic acid and red phosphorus.Acetylated sugar isothiocyanates have been synthesized from related bromides using lead thiocyanate in sodium dried xylene under microwave irradiation.To afford products, the solvent was distilled off and sticky residue obtained was triturated with petroleum ether (60-80 o C).The products were purified by chloroform-ether.The products were found to be desulfurized when boiled with alkaline plumbite solution.

Synthesis of tetra-O-acetyl-β-D-glucosyl isothiocyanate and tetra-O-acetyl-β-Dgalactosyl isothiocyanate under microwave irradiation
To a solution of tetra-O-acetyl-α-D-glucosyl bromide (Ia) (0.024 M, 10.0 g) dissolved in sodium dried xylene (25 mL) was added lead thiocyanate (6.0 g).The reaction mixture was then kept under microwave irradiation for about 25 min.at constant power P-70, the temperature of reaction mixture remain constant at 130-140 o C. The resultant solution was then cooled and separated lead bromide was removed by filtration.The solvent was distilled off and sticky mass obtained as residue was triturated with petroleum ether (60-80 o C).A pale yellow solid (8.5 g) was obtained.The product (IIa) was purified by chloroform-ether.m.p. 112 o C. (Scheme 1).

Synthesis of hepta-O-acetyl-β-D-lactosyl isothiocyanate and hepta-O-acetyl-β-Dmaltosyl isothiocyanate under microwave irradiation
To a solution of hepta-O-acetyl-α-D-lactosyl bromide (IV) (0.014 M, 10.0 g) dissolved in sodium dried xylene (25 mL) was added lead thiocyanate (6.0 g) in a 50 mL beaker.The reaction mixture was then kept under microwave irradiation for about 40 min.at constant power P-70, the temperature of reaction mixture remain constant at 130-140 o C. The resultant solution was then cooled and separated lead bromide was removed by filtration.The solvent was distilled off and sticky mass obtained as residue was triturated with petroleum ether (60-80 o C).A pale yellow solid (7.2 g) was obtained.The product (V) was purified by chloroform-ether.m.p. 164 o C. (Scheme 2).

Table 1 .
. Physical data of acetylated sugar isothiocyanates and comparative study of conventional vs. microwave method

Table 2 .
Physical data of acetylated sugar thiocarbamides and comparative study of conventional vs. microwave method