An investigation of direct C-alkylation of 2,4-oxazolidinedione and 5-phenyl-2,4-oxazolidinedione utilizing dialkali salt intermediates

Abstract

The effects of solvent, base strength, nature of halide, number of equivalents of base, and number of equivalents of halide on the course of C-alkylation of 2,4-oxazolidinedione and 5-phenyl-2,4-oxazolidinedione were investigated.

The highest isolated yield (49%) of 5-benzyl-5-phenyl-2,4-oxazolidinedione was obtained using 2.1 equivalents of lithium amide in liquid ammonia followed by alkylation with 1.1 equivalents of benzyl chloride. Although the yield of 5-benzyl-5-phenyl-2,4-oxazolidinedione using lithium diisopropylamide in THF-hexane-HMPA was only 39% (determined by pmr analysis), the addition of HMPA as a co-solvent had a beneficial effect on the ratio of 5-phenyl-2,4-oxazolidinedione to the benzyl derivative. The addition of HMPA as a co-solvent in the ethylation of 5-phenyl-2,4- oxazolidinedione using lithium diisopropylamide in THF-hexane increased the yield of the ethyl derivative by 60% over that obtained in the absence of HMPA.

Using potassium amide in liquid ammonia, lithium amide in liquid ammonia, lithium diisopropylamide in THF-hexane, or lithium diisopropylamide in THF-hexane-HMPA failed to produce 5-benzyl-2,4-oxazolidinedione in a significant yield.

Several attempts were made to form the dianion of oxindole and selectively alkylate it at the 3-position without the interference of dialkylation at that position. No evidence was obtained which indicated that the dianion had been successfully formed, and the major products afforded from these attempts were the 3,3-dialkyl derivatives of oxindole.