Thalidomide and its derivatives have great potentials in immune therapy. This research note presented that heating the mixture of phthalic anhydride or its chloro or nitro substituted derivatives and L-glutamine in vacuum afforded thalidomide 1 and its corresponding derivatives 2—5 directly in yields 24%47%. Among them, compound 4 is the material in the synthesis of 3-amino and 3-amino-3′-fluoro substituted thalidomide. Compared with traditional methods, this method is more direct and convenient.
The method of Michael addition reaction of thiophenol with intramolecular hydrogen bond in an aqueous medium was reported. The aqueous reactive medium includes saturated sodium bicarbonate solution and catalytic amount of tetrabutylammonium bisulfate. 2-Hydroxythiophenol,2-aminothiophenol,2-carboxythiophenol,ethyl acrylate and arcylonitrile were selected as model molecules to demonstrate the method. It is found that the reaction can be accomplished rapidly at room temperature with a high yield,and no mercapto-coupling byproduct formed.
