Synthesis of Perfluoroalkyl-Substituted Azines via Nucleophilic Substitution of Hydrogen with Perfluoroisopropyl Carbanions

Abstract

Perfluoroisopropyl carbanions generated in situ by treatment of perfluoropropene (HFP) with solid KF in the appropriate solvents add to N-alkylpyridinium, quinolinium, and other azinium salts to give reasonably stable N-alkyldihydroazines containing a perfluoroisopropyl group. In most cases, addition proceeds in position 2 of the heterocyclic ring. Stability of these dihydroazines depends on the nature of the N-alkyl group and other substituents present in the azine ring. The least stable of them were converted into their stable C-trifluoroacetyl derivatives in reaction with trifluoroacetic anhydride. Treatment of N-benzyl- or N-p-methoxybenzyl-2-perfluoroisopropyl dihydroazines with oxidizing agents such as DDQ or cerium(IV) ammonium nitrate results in cleavage of the benzylic C-N bond followed by oxidation of the ring, giving pyridines or quinolines with a perfluoroisopropyl group in the aromatic ring. On the basis of these findings, a new protocol for introduction of perfluoroalkyl substituents into azine rings was elaborated via oxidative nucleophilic substitution of hydrogen. It involves three chemical steps: (i) alkylation of azine with p-MeOC6H4CH2Br, (ii) reaction of the resulting salt with fluorinated carbanions generated in situ from HFP and KF, and (iii) N-deprotection and aromatization of the isolated dihydroazine on treatment with CAN. The first two reactions, (i) and (ii), can be performed as a one-pot operation.