Azo-anions in organic synthesis

Thesis



Novel synthetic applications of ambident azo-anions derived from hindered hydrazones have been investigated. Reaction with electrophiles occurred predominantly at carbon as the N-addition pathway was sterically retarded. Trityl, diphenyl-4-pyridylmethyl (DPP) benzhydryl, and t-butyldiphenylmethyl (BDP) hydrazones of various aldehydes and ketones were prepared in good yields from the corresponding hydrazines and carbonyls in aqueous methanol. The lithium salts derived from trityl and DPP hydrazones, by treatment with methyl lithium at -55°C, reacted with aldehydes and ketones to generate azo-alkoxides. These could be diverted to alcohols,by sequential protonation and spontaneous homolysis (about -20°C) in the presence of ethanethiol, or to alkenes,by treatment with phosphorus trichloride at -78 G followed by azo-homolysis. The reactions enabled efficient reductive cross-coupling of aldehydes and ketones. The mechanism of the alkene forming reaction was investigated. Anions of benzhydryl hydrazones were found to react inefficiently by a G-addition pathway giving mainly N-addition products.

Anions of BDP hydrazones conveniently gave excellent yields of azo-alkanes upon treatment with alkyl halides,but no products were obtained on reaction with carbonyl electrophiles. The azo-alkanes could be isolated and purified and acted as key intermediates for several synthetically useful transformations. Homolysis in refluxing benzene with thiophenol gave alkanes in good yields. Phenylselenenyl-, bromo-, and chloro-alkanes,and β-alkylstyrenes were generated when thiol was replaced by diphenyl diselenide, N-bromosuccinimide, N-chlorosuccinimide and β-nitrostyrene respectively.

Treatment of the azo-alkanes with trifluoroacetic acid generated benzophenone alkylhydrazones. These were dissolved in ethanol with concentrated hydrochloric acid, thereafter hydrolysis yielded alkylhydrazines or treatment with hydrogen (1 atm., 50°C, 20h) over 10% Pd/C generated primary amines by a novel use of carbonyls as α-aminocarbanion equivalents.

Authors: Newington, I; I. M. Newington

• Publication date: 1985
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Subjects: Organic compounds; Azo compounds; Synthesis