Vicarious nucleophilic substitutions , aromatic hydrogens

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

Vicarious nucleophilic substitution of hydrogen in nitro aromatics and nitro heteroaromatics 07CJO17. 

Vicarious nucleophilic substitution of hydrogen is described in several reviews [158, 159, 161]. The special character of vicarious nucleophilic substitution of hydrogen (VNSH) is that the nucleophile is a carbanion that must contain a leaving group X attached to the carbanionic centre. The first step is a fast reversible addition of carbanion to the nitroaromatic ring, followed by base-induced p-elimination of HX from the intermediate o-adduct 77. Protonation is then necessary to restore the aromaticity of the compound. Two equivalents of base must be used, the first to deprotonate the CH-acidic compound to form the carbanion the second is responsible for the HX elimination (Scheme 107) [168]. 

The alkylation of aromatic nitro compounds by carbanions having a leaving group at the nueleophilic center is called Vicarious Nucleophilic Substitution of Hydrogen (VNS) (Seheme 36.1). This reaction is one of the scarce general processes that result in the formal nucleophilic aromatic substitution of hydrogen. 

Some derivatives of the [l,2,4]triazolo[4,3-3]pyridazine ring system 33 were subjected to a special type of nucleophilic substitution called vicarious nucleophilic substitution (VSN) <2006TL4259>. In the course of this transformation a formal substitution of az aromatic hydrogen atom - occurring via an addition-elimination mechanism - takes place. 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

A variety of methods for the direct amination of nitrobenzene, that do not require halogenated aromatic compounds, have been reported, including both vicarious (eliminative) [16, 17,19,42] and oxidative versions of nucleophilic substitution of hydrogen. Recently, we have described the aminatimi of 1,3-dinitrobenzene promoted by fluoride ions through photochemical activation [43], Also, the use of KMn04 as oxidant is of great practical value [3,44]. 

Replacement of an aromatic fluorine atom by a carbon nucleophile is facilitated by the presence of electron-withdrawing groups [82] (equation 44) Replacement of an activated aryl hydrogen can occur in preference to a nonactivated aryl fluorine [S3] (equation 45) in reactions known as vicarious substitutions. 

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