Oxidative Nucleophilic Substitution of Hydrogen in Nitroarenes

Abstract

Carbanions of 2‐phenylpropionitrile were found to add to nitroarenes in liquid ammonia to form σH adducts, which were oxidized with KMnO4 to yield products of oxidative nucleophilic substitution of hydrogen (ONSH) in the position para to the nitro group. Treatment of the carbanion‐nitroarene system with methyl iodide at ‐70°C indicated that the addition proceeds almost to completion. Thus, for the first time, the persistence of σH adducts, formed between free anions and mononitroarenes, has been demonstrated. It was also shown that KMnO4 oxidizes σH adducts to nitrobenzene faster than it does carbanions. This selective ONSH in the para positions of nitroarenes is a general process. However, some substituents hinder or inhibit the oxidation step.

Aza-ortho-xylylenes in Organic Synthesis

“…Lau et al have developed methodologies for the generation of aza-ortho-xylylenes by the thermal [89,91] or Lewis acid-catalyzed [90,95] 1,4-elimination of water from ortho-aminobenzyl alcohols (Scheme 41, see also Schemes 42,45,and 47). The ortho-quinone methide imines formed in these reactions undergo intermolecular and intramolecular cycloadditions to afford condensed heterocycles, with high levels of stereocontrol usually being observed.…”

Synthesis of 4-aryloxy-7-nitrobenzofurazan derivatives from 4-chloro-7-nitrobenzofurazan and various phenoxide anions (including pharmaceuticals) in the presence of crown ethers

“…Among the three possible types of aromatic nucleophilic substitution (normal S N Ar displacement of activated halogen via a Meisenheimer complex [24,25,41], substitution of hydride, possibly in the presence of an oxidant [24,25,41], and vicarious nucleophilic substitution of an ®-situated hydride anion in the presence of an oxidant [41][42][43][44][45][46][47]), thē rst one was involved in our case [48]. The high yields indicated in Table 1 for the aroxide salts were possible by the appropriate choice of the cation: the sodium salts of 7e,g and 8 and the potassium salts of the remaining phenolic compounds.…”

Oxidative nucleophilic substitution of hydrogen in nitroarenes with an oxazoline stabilised carbanion

“…Another efficient base solvent system for the ONSH reaction with carbanions is NaNH 2 in liquid ammonia with KMnO 4 as the oxidant. 15 We have found that this system can also be applied for the reaction of 1. Treatment of 1 with NaNH 2 in liquid ammonia and subsequently with nitrobenzene and KMnO 4 gave 2a in an excellent yield (90%).…”