REACTIONS OF ALPHA-SUBSTITUTED ISOPROPYLPYRIDINES AND THEIR DERIVATIVES WITH NUCLEOPHILES

JAMES KEITH DOTY, Purdue University

Abstract

Recently, Feuer and co-workers('1) disclosed that the reaction of 2-nitro-2-(4-pyridyl)propane (1) with the carbanion of 4-isopropyl-pyridine in liquid ammonia, which afforded 2,3-bis(4-pyridyl)-2,3-dimethylbutane (2), proceeded by electron transfer processes. While these processes have been extensively investigated in the related p-nitrocumyl system('2), this represented the first case in which substitution at saturated carbon proceeds via free radical and radical anion intermediates in (pi)-deficient heterocylic compounds. Therefore, a comprehensive study of the reaction of compound 1 with nucleophiles in dipolar aprotic solvents was undertaken with the hope that the synthetic utility of the radical anion substitution reaction could be advanced. When 2-nitro-2-(4-pyridyl)propane (1) was treated with alkane-nitronates or sodium thiophenoxide, excellent yields of the tertiary substitution products were obtained. Moreover, these reactions were shown to proceed via radical anion chain pathways because they were found to be photochemically initiated and completely inhibited in the presence of catalytic amounts of various nitroarenes and di-t-butylnitroxide. Furthermore, when these reactions were carried out in the presence of oxygen, a known scavenger of free radicals, the C-alkylation process was suppressed and compound 1 was converted into the tertiary alcohol, 2-(4-pyridyl)-2-propanol. The reaction of compound 1 with sodium thiomethoxide afforded a mixture consisting of the tertiary thioether, the primary thioether, and the olefin, 4-isopropenylpyridine. During the course of this study, a novel catalytic reaction was discovered. Addition of as little as 25 mole % nitrobenzene increased the rate of this reaction substantially. Furthermore, the tertiary thioether was the only product and not a trace of the isomeric primary thioether could be detected. The tertiary thioether was found to react further and afforded the hydrocarbon, 4-isopropylpyridine, when the reaction time was extended. The formation of the hydrocarbon and the tertiary thioether are also believed to occur by radical anion processes. However, the formation of the primary thioether was found to occur by a Michael Type Addition of sodium thiomethoxide to 4-isopenylpyridine. Furthermore, the formation of this olefin is believed to occur by competitive radical and ionic elimination pathways. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of school.) UMI References ('1)H. Feuer, J. Doty and J. P. Lawrence, J. Org. Chem., 38, 417 (1973).('2)N. Kornblum, Proc. Int. Cong. Pure Appl. Chem., 23rd, 4, 81 (1971).

Degree

Ph.D.

Subject Area

Organic chemistry

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