The formation and chemistry of certain heterocyclic dianions

Abstract

Glutarimide was converted to its dianion by treatment with two molecular equivalents of sodium amide in liquid ammonia. The dianion underwent C-alkylation with numerous alkyl halides, to form 2-alkylglutarimides. Certain of these 2-alkyl derivatives were hydrolyzed to the corresponding 2-alkylglutaric acids. Carbonyl addition reactions of the glutarimide dianion with benzophenone, 9-fluorenone, cyclohexanone, and anisaldehyde yielded tertiary and secondary alcohol derivatives which were subsequently dehydrated to form unsaturated glutarimides. The two diastereomeric alcohols resulting from condensation of the dianion with anisaldehyde were separated and their configuration assigned. In addition, glutarimide dianion also underwent aroylation with certain aromatic esters to afford 2-aroylglutarimides, which were subsequently hydrolyzed to the appropriate 4- aroylbutyric acids. The dipotassio salt of glutarimide was equally as reactive as the disodio salt for carbonyl addition reactions, but afforded lower yields for alkylation. The inactivity of dilithioglutarimide whose formation was attempted using lithium amide in liquid ammonia as well as n-butyllithium in THF-hexane, is discussed. The dianion of 2-benzylglutarimide was prepared by treatment of this substituted heterocycle with two equivalents of sodium amide in liquid ammonia. Benzylation of this dianion with benzyl chloride produced two diastereomers of 2,4-dibenzylglutarimide, which were separated and identified. The dianion of 3,5-morpholinedione was formed by treatment of this neutral compound with two molecular equivalents of sodium amide in liquid ammonia. Alkylations with ~-butyl bromide, benzyl chloride and 4-chlorobenzyl chloride proceeded at the carbanion site. Aldol condensation of the dianion with benzophenone was accomplished, although similar reactions with several aromatic aldehydes failed. In addition to alkylation and aldol-type condensations, the disodio salt underwent Claisen-type condensation with methyl benzoate in liquid ammonia. The yields obtained from the reactions of the dianion of 3,5-morpholinedione with electrophilic reagents were lower than for the analogous reactions of the dianion of glutarimide. A rationale is given for these results. Several electrophilic condensations were effected at the carbanion site of the dianion of 3,5-thiomorpholinedione, formed by treatment of this cyclic imide with two molecular equivalents of sodium amide or lithium amide in liquid ammonia. Alkylations of the dianion were effected with n-butyl bromide and benzyl chloride. Considerable polyalkylation was observed when the salts were treated directly with alkyl halide, although the dilithio salt afforded less side product than the disodio salt. Inverse addition of the dilithio salt to excess halide yielded predominantly the monoalkyl derivative. A mechanism for polyalkylation, along with a discussion of its control, is presented. The disodio salt underwent carbonyl addition with benzophenone to afford a 2,4-diadduct instead of the expected monocondensation product. Maximum yields of the adduct were obtained after short reaction times whereas longer times afforded only starting materials. An explanation for the formation of the unexpected diadduct is given. Finally, the disodio salt was allowed to react with methyl benzoate in liquid ammonia, to form the benzoyl derivative.