Nucleophilic aromatic substitution 3- nitrothiophene

Some theoretical aspects of thiophene reactivity and structure have also been discussed, for example the kinetics of proton transfer from 2,3-dihydrobenzo[6]thiophenc-2-onc <06JOC8203>, the configuration of imines derived from thiophenecarbaldehydes <06JOC7165>, and the relative stability of benzo[c]thiophene <06T12204>. The kinetics of nucleophilic aromatic substitution of some 2-substituted-5-nitrothiophenes in room temperature ionic liquids have also been investigated <06JOC5144>. 

Nucleophilic aromatic substitution reactions of nitro-substituted thiophenes have been utilized to prepare biologically active thiophenes including reverse transcriptase <02H(57)97> and nitric oxide synthase <02JHC857> inhibitors. The addition-elimination reaction of 2-chloro-3-nitrothiophene (56) with metallated indole 57 afforded 58 which was transformed into the corresponding thiophene-fused azepino[5,4,3-cd]indoles 59 <02H(57)1831>. 

In most cases, nitrothiophenes or bromo-substituted nitrothiophenes have been used as the substrates for aromatic nucleophilic substitutiOTi. Both bromo and nitro groups can be substituted by oxygen, nitrogen or sulfur nucleophiles [156]. 

Nice examples of nucleophilic substitution on a thiophene ring are represented by nucleophilic substitutions of 5-acetyl-2-chloro-3-nitrothiophene (Scheme 103) [164], The acetyl group, as a second electron-withdrawing group, in addition to the nitro group, was necessary to support successful nucleophilic substitution. Various nucleophiles were effective, including aliphatic and aromatic V-nucleophiles, aliphatic 0-nucleophiles as well as aliphatic S-nucleophiles (Scheme 103) [164],... 

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