Unexpected Cleavage of N‐N Bonds of Pentafluorophenylhydrazones – Formation of Nitriles by a Radical Fragmentation Reaction

Abstract

A novel method of the preparation of (hetero)aryl nitriles based on the fragmentation of the corresponding pentafluorophenylhydrazones is described. The synthesis is metal‐free, proceeds in neutral conditions with no need of protecting group application and provides most nitriles in moderately good yields. The synthesis was performed on ten pentafluorophenylhydrazones with different functional groups within the carbonyl part – the reaction was found to be partially substrate selective. The reaction prefers substrates with aromatic electron donating substituents on the carbonyl part of the hydrazone. The second reaction product, 2,3,5,6‐tetrafluoroaniline, can be easily separated by vacuum distillation. Although the reaction mechanism is yet to be ascertained, all synthetic and spectroscopic data suggest a radical reaction mechanism.

Mass spectrometrical and quantum‐chemical study of pentafluorophenylhydrazones

“…Studied aromatic and heteroaromatic derivatives of pentafluorophenylhydrazones 1 present one principal fragmentation occurring after breaking the N–N bond of the hydrazone bridge, which is not typical for aliphatic analogues. This fact confirms our experimental results of the reaction of the title pentafluorophenylhydrazones with anions, which give us similar products and also parallel nucleophilic substitution of the fluorine atom in position 4 9 …”

“…From this point of view, we can consider the influence of the strong electron‐withdrawing effect of the pentafluorophenyl nucleus onto –NH–NCH– fragment substituted from the opposite side with alkyl, aryl, electron‐rich five‐membered heteroaryl nuclei bearing various substituents in different positions. Such hydrazones 1 were prepared from logical components, but their chemical reaction with azide or cyanide anion, respectively, gave surprisingly unexpected products, 2,3,5,6‐tetrafluorophenylaniline and corresponding nitrile 9 . Thus, breaking of the NH–N is the crucial moment to study the behavior of the title molecules.…”

“…The synthesis of the pentafluorophenylhydrazones 1 , published previously in Bortňák et al 9 , was properly modified (Scheme 1). The synthesis is based on the condensation of the ethanolic solution of pentafluorophenylhydrazine with an ethanolic solution of appropriate aldehyde and with a catalytic amount of hydrochloric acid according to the following scheme:…”

“…Because preliminary results were very repugnant, we decided to extend the set of the studied compounds to 21 derivatives. Our set included the sterically hindered alkyl-substituted derivative 1u, variously substituted phenylderivatives with electron-withdrawing (1i and 1j), activated (1a and 1b) or strongly activated (1c-1h) derivatives 1p 5 0 -bromo-2,2 0 -bithiophene-5-yl Bortňák et al 9 and electron-rich five-membered heterocycles with diene (furane derivatives 1r-1t) with less (1k) or more aromatic character (thiophene derivatives 1l-1q) bearing different substituents in positions not only 5-but also 4-(1q and 1m) and finally bithiophene derivatives 1n and 1p where we have prepared also the corresponding hydrazone from the deuterated aldehyde 1o for special study.…”