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Synthesis 2011(15): 2341-2356  
DOI: 10.1055/s-0030-1260668
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© Georg Thieme Verlag Stuttgart ˙ New York

Nucleophilic Substitution of Hydrogen in Nitroarenes: A New Chapter of Aromatic Chemistry

Mieczysław Mąkosza*
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax: +48(22)6326681; e-Mail: icho-s@icho.edu.pl;
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Publication History

Received 11 February 2011
Publication Date:
15 June 2011 (online)

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Abstract

Basic concepts, mechanistic principles and the broad application of nucleophilic substitution of hydrogen in nitroarenes and other electron-deficient arenes in organic synthesis are presented in a concise way. It was shown that the initial process between nucleophiles and (halo)nitroarenes is a fast and reversible addition - in positions occupied by hydrogen - to form anionic σH adducts that can then be converted into products of nucleophilic substitution of hydrogen in a few ways. Only when these pathways for rapid conversion of the σH adducts into products of nucleophilic substitution of hydrogen are not available, do the σH adducts dissociate. The subsequent slower formation of σX adducts, followed by departure of X anions, results in the conventional nucleophilic aromatic sub­stitution of halogens, namely the SNAr reaction. Thus the SNAr reaction is a secondary ipso substitution, whereas nucleophilic substitution of hydrogen is a primary fast process. It is therefore necessary to introduce corrections in appropriate chapters of textbooks and monographs.

1 Introduction

2 Oxidative Nucleophilic Substitution of Hydrogen (ONSH)

3 Vicarious Nucleophilic Substitution of Hydrogen (VNS)

4 Other Ways of Converting the σH Adducts

5 Application of Nucleophilic Substitution of Hydrogen in Organic Synthesis

5.1 Introduction of Carbon Substituents

5.2 Introduction of Heteroatom Substituents

5.3 Construction of Carbo- and Heterocyclic Rings

6 Concluding Discussion

Key words

oxidative nucleophilic substitution - vicarious nucleophilic substitution - mechanism - electron-deficient arenes

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Mąkosza, M.; Wojciechowski, K. In Targets in Heterocyclic Systems, Vol. 14; Attanasi, O.A.; Spinelli, D. Eds.; Società Chimica Italiana: Roma, 2010.