Reduction of the Ring

It has been shown that some reductases can mediate the reduction of nitro groups and of the ring to Meisenheimer-type complexes that are analogous to those that have been observed in nitrophenols (which are described later)  

Dioxygenation may result in the elimination of nitrite in reactions that are analogous to the elimination of sulfite from aromatic sulfonates, or halogen from 2-halobenzoates. As an alternative to dioxygenation, toluene-3- and toluene-4-monooxygenases can transform nitrobenzene to 4- or 3-nitrophenol, with the former dominating (Fishman et al. 2004)  

The degradation of 2,4,6-trinitrotoluene under aerobic conditions is strictly dependent on the reduction of one or more nitro groups to amino groups before dioxygenation (Fiorella and Spain 1997 Johnson et al. 2001). 

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The aerobic degradation of several azaarenes involves reduction of the rings at some stage, and are discussed in Chapter 10, Part 1. Illustrative examples include the degradation of pyridines (3-alkyl-pyridine, pyridoxal) and pyrimidines (catalyzed by dihydropyrimidine dehydrogenases). Reductions are involved in both the aerobic and the anaerobic degradation of uracil and orotic acid. 

The fermentation of 3-hydroxybenzoate by Sporotomaculum hydroxybenzoicum produces acetate, butyrate, and CO2, with benzoate as a transient intermediate (Brauman et al. 1998). However, although the degradation of 3-hydroxybenzoate by Thauera aromatica begins with the formation of the CoA-ester, this is followed by the reduction of the ring with retention of the original hydroxyl group (Laempe et al. 2001). 

Similar reactivity is realized with 2-acetylthiophene using triethylsilane with aluminum chloride.259 Treatment of the ethylene glycol acetal of 2-thiophenecar-baldehyde with Et3SiH/TFA results in reduction of the ring and oxidation of the side chain to the silylated carboxylic acid (Eq. 119),260 whereas similar treatment of 2-thiophenecarbaldehyde gives 2-methyltetrahydrothiophene and 2-... 

Reductive dehalogenation by catalytic hydrogenation of 3-chloro-,233 l,3-dichloro-2-phenyl-, and 2-benzyl-l,3-dichloro-4,7-phenanthrolines can be accomplished without accompanying reduction of the 4,7-phenanthroline ring skeleton101 but with l,3-dichloro-2-methyl- and 1,3-dichloro-2-ethyl-4,7-phenanthrolines mixtures of products were obtained due to concomitant reduction of the ring system. 

Pyrimidine and simple alkyl derivatives are not reduced by NaBH4. Lithium aluminum hydride converts pyrimidines to di- or tetra-hydro derivatives. In general, electron-withdrawing substituents promote reduction of the ring, while electron-releasing substituents have the opposite effect. The metal hydride may act as a base and abstract a proton from the a-position in a substituent, in which case the anionic substrate may resist reduction in the ring. 

The use of other metal catalysts in attempted reductions of halo-naphthyridines has resulted in reduction of the ring or, at best, in the formation of mixtures. 

The 2,4,6-isomer reacts with reduction of the ring, and in competitive expts was found to react more rapidly than the unsymmetrical isomers... 

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