Oxidative nucleophilic substitution of hydrogen ONSH

The oxidative nucleophilic substitution of hydrogen (ONSH) in 2-nitrobenzo[/ ]thiophene involves the initial reversible addition of the nucleophile to the 2,3-double bond. This is discussed in Section 3.10.4.2.1. 

Since hydride anions are unable to depart spontaneously from the anionic adducts, they should be removed by external oxidants. However, possibilities for conversions of the adducts into products of oxidative nucleophilic substitution of hydrogen (ONSH) appear to be limited, since nucleophiles, and particularly carbanions, are usually sensitive to oxidation. Thus, ONSH can be feasible in two major cases ... 

Straightforward approach to benzo[ r]selenophenes in which 4-(3-nitroaryl)-1,2,3-selenadiazoles undergo a base-promoted transformation to an intermediate eneselenoate followed by 5-exo-trig cyclization. The regiochemistry of the cyclization is dependent upon the conditions of the reaction. In the presence of an oxidant, the adduct is formed rapidly by the oxidative nucleophilic substitution of hydrogen (ONSH, SnAt ) followed by oxidative aromatization of the rapidly formed adduct. In the absence of an oxidant, the reaction proceeds via intermediate formation of the adduct, followed by nucleophilic aromatic substitution of the halogen (SnAt ). 

Hydride anions cannot depart spontaneously from the a -adducts thus, they should be removed by external agents-oxidants. Oxidation of the a -adducts by external oxidants seems to be the obvious way to products of oxidative nucleophilic substitution of hydrogen (ONSH). However, taking into account the reversibility of the formation of the a -adducts and susceptibility of majority of nucleophiles to oxidation, the ONSH is limited to three variants (i) nncleophiles are insensitive to the oxidants used, (ii) the equilibrium of the addition is shifted toward o -adducts, and (iii) the addition is an irreversible process ... 

Active carbanions are prone to substitute hydrogen of nitroaromatic compounds the substitution usually takes place either ortho or para to the nitro group. The anionic On-adduct generated as a result of nucleophilic addition can be converted into the final product by various mechanisms [167]. Most often exemplified are vicarious nucleophilic substitution (VNS) and oxidative nucleophilic substitution of hydrogen (ONSH). 

Another mechanism of nucleophilic substitution which is relevant to thiophenes is oxidative nucleophilic substitution of hydrogen (ONSH). An example is the reaction of 2-nitrothiophene with the carbanion originating from diphenylacetonitrile. This carbanion forms On-adducts only at a position para to a nitro group for steric reasons. Thus, after addition of an oxidant KMn04, the final product is 83 (Scheme 116) [173]. 

However, 4-methyl-2-nitrothiophene under the same reaction conditions, and with various amines, gave only 3-methyl-2-amino-5-nitrothiophenes - products of oxidative nucleophilic substitution of hydrogen (ONSH) at C-5, in good yields with no trace of ring opening (Scheme 128) [183]. 

The S,jAr reaction is circumscribed by the major mechanisms of nucleophilic aromatic substitution the most common S, Ar addition-ehmination (Chapter 6), the oxidative nucleophilic aromatic substitution of hydrogen (ONSH Chapter 11), the benzyne mechanism (Chapter 12), and the radical-nucleophilic aromatic substitution Sj j l (Chapter 10). The chiral inductor can be bonded (Section 8.2) or nonbonded to the reactants (Section 8.3) (Scheme 8.1). 

ONSH Oxidative nucleophilic aromatic substitution of hydrogen... 

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