Rearrangement NIH shift

Arene oxides can be intermediates in the bacterial transformation of aromatic compounds and initiate rearrangements (NIH shifts) (Dalton et al. 1981 Cerniglia et al. 1984 Adriaens 1994). The formation of arene oxides may plausibly provide one mechanism for the formation of nitro-substituted products during degradation of aromatic compounds when nitrate is present in the medium. This is discussed in Chapter 2. 

Unusual pathways have been found in the bacterial degradation of a number of 4-hydroxybenzoates and related compounds, and in some of them rearrangements (NIH shifts) are involved ... 

A rearrangement (NIH shift) occurred during the transformation of 2-chlorobiphenyl to 2-hydroxy-3-chlorobiphenyl by a methanotroph, and is consistent with the formation of an intermediate arene oxide (Adriaens 1994). The occurrence of such intermediates also offers plausible mechanisms for the formation of nitro-containing metabolites that have been observed in the degradation of 4-chlo-robiphenyl in the presence of nitrate (Sylvestre et al. 1982). 

Gentisate is formed by a strain of Bacillus sp. in an unusual rearrangement from 4-hydroxybenzoate (Crawford 1976) that is formally analogous to the formation of 2,5-dihydroxyphenylacetate from 4-hydroxyphenylacetate by Pseudomonas acidovorans (Hareland et al. 1975). Similarly, the metabolism of 4-hydroxybenzoate by the archaeon Haloarcula sp. strain D1 involves the formation of 2,5-dihydroxybenzoate (Fairley et al. 2002). All these reactions putatively involve an NIH shift. 

Recently, the PCB-biodegradative capabilities of methanotrophs have been demonstrated (Adriaens, 1994). In this study, 2-CB was oxidized by a methanotrophic culture (CSC1) to a hydroxylated chlorobiphenyl intermediate identified as 2-hydroxy-3-chlorobiphenyl. This intermediate indicated that the metabolite was formed via a concerted oxidation involving an arene oxide which rearranges spontaneously via an NIH shift. No studies have shown, however, that methanotrophs can degrade more highly chlorinated PCBs, and their utility for bioremediation processes does not seem promising. 

The mechanism of the NIH shift was not clearly understood until naphthalene 1,2-oxide (197) was isolated in the metabolism of 1-T-naphthalene (198) with hepatic monoxygenases the oxide then rearranges to 1-naphthol with migration of tritium from the 1- to the 2-position.112,113... 

On the basis of these observations, the NIH shift was attributed to a chemical sequence involving oxidation of the aromatic ring to an arene oxide, opening of the oxide to an ionic intermediate, and finally rearrangement to a phenol with migration of a substituent. When appropriately labeled arene oxides were prepared, shifts to the extent of about 95% were observed. 

This rearrangement is known as the NIH shift, after its discovery at the National institutes of Health at Bethesda. Maryland. 

This rearrangement was studied as a biomimetic version of the NIH shift. Write a mechanism for the reaction. Do you consider it a good model reaction If not, how might it be made better ... 

Fig. 10). Internal Claisen rearrangement on chorismic acid yields prephenic acid en route to phenylalanine. During the course of the hydroxylation of phenylalanine to tyrosine, there is a characteristic NIH shift of... 

In enzymatic reactions, the NIH shift is generally thought to derive from the rearrangement of arene oxide intermediates, but other pathways have been suggested. NIH is the acronym of the National Institutes of Health, Bethesda, Maryland, where the shift was discovered. 

Mechanistically, it has been proposed that the reaction proceeds predominantly via epoxidation of the aromatic species 28, which leads to unstable arene-oxides 29-31 (equation 47). Rearrangement of the arene-oxides 29-31 involving the migration of a hydride anion (NIH-shift) forms the phenolic product 32 or 33. Alternative flavin-dependent oxidases have been proposed to involve a hydroperoxide intermediate. ... 

Naphthyl acetates, Fries rearrangement of 639 Naphthylamines—see also 8-Hydroxy-A, Ai-dimethyl-1-naphthylamine as phenol precursors 401, 402 Naringin, complexes of 365 National Institute of Health (NIH) shift 14 Negative ion chemical ionization (NlCl) mass spectrometry 310, 314-316 Negishi reaction 1406 Nematic liquid crystals 372-375 Neolignans 1278... 

Rearrangement—These are particularly important among anaerobic bacteria where they involve coenzyme-B12. The unrelated rearrangement of the substituents on aromatic rings (the NIH shift) is well established particularly among fungi. 

When an arene oxide undergoes rearrangement, the three-membered epoxide ring opens, picking up a proton from a species in the solution. Instead of immediately losing a proton to form phenol, the carbocation forms an enone as a result of a 1,2-hydride shift. This is called an NIH shift because it was first observed in a laboratory at the National Institutes of Health. Removal of a proton from the enone forms phenol. 

The existence of the NIH shift was established by determining the major product obtained from rearrangement of the following arene oxide, in which a hydrogen has been replaced by a deuterium ... 

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