N-Oxides deoxygenation

Tong, W., Chowdhury, S. K., Chen, J. C., Zhong, R., Alton, K. B. and Patrick, J. E. Fragmentation of N-oxides (deoxygenation) in atmospheric pressure ionization investigation of the activation process. Rapid Comm. Mass Spectrom. 15 2085-2090, 2001. 

Nucleophilic substitution occurs in positions a and y to the N-oxide group. In nearly all these reactions deoxygenation occurs giving the substituted heterocychc amine. 

Treatment of N-oxides with phosphoms trichloride provides a good method for deoxygenation (eq. 12) to obtain the free base. 

Treatment of pyridazine 1-oxides with phosphorus oxychloride results in a-chlorination with respect to the N-oxide group, with simultaneous deoxygenation. When the a-position is blocked, substitution occurs at the y-position. 3-Methoxypyridazine 1-oxide, for example, is converted into 6-chloro-3-methoxypyridazine and 3,6-dimethylpyridazine 1-oxide into 4-chloro-3,6-dimethylpyridazine. 

Nitropyridazines are reduced catalytically either over platinum, Raney nickel or palladium-charcoal catalyst. When an N-oxide function is present, palladium-charcoal in neutral solution is used in order to obtain the corresponding amino N-oxide. On the other hand, when hydrogenation is carried out in aqueous or alcoholic hydrochloric acid and palladium-charcoal or Raney nickel are used for the reduction of the nitro group, deoxygenation of the N- oxide takes place simultaneously. Halonitropyridazines and their N- oxides are reduced, dehalogenated and deoxygenated to aminopyridazines or to aminopyridazine N- oxides under analogous conditions. 

Because quinoxalines are often converted into their N-oxides in order to facilitate other reactions, subsequent removal of the oxide entity without untoward effects is quite important. The choice of a reagent for such deoxygenation is frequently governed by the type(s) of passenger group present direct comparisons of several methods have bee presented. " The following classified examples illustrate most of the possibilities available. 

The reduction of the N-oxide moiety to produce the heterocycle parent compounds Bfz and Fz has been one of the most studied reactions for these systems. In general, the procedures describe mild conditions and regioselect-ivity. In Table 2, substrates, conditions, products, and comments for the most recent reported deoxygenations are shown. 

The role of oxazirdines as intermediates in the rearrangement of heteroaromatic N-oxides has not been fully established although in most cases the formation of photoproducts can best be rationalized in terms of such intermediates. Rearrangement appears to be singlet-derived and competes with triplet-derived deoxygenation. 

In other reactions, 1,2,3-dithiazole N-oxides were proposed as intermediates which underwent deoxygenation. Thus, l-oximino-3-phenylindene formed 1,2,3-dithiazole 134 (1992JHC639, 1993JCS(P1)769 Scheme 67). 

Deoxygenation of the N-oxide 194 was achieved using hexachlorodisilane in chloroform.168... 

The only alkyl group reported as reductively removed is the di-phenylmethyl substituent from N3 in compound 165.153 Deoxygenation of N-oxides can be done thermally (heating in toluene with oxygen transfer to solvent) for compounds of type 166,44 or more commonly by use of phosphorus derivatives, as described for compounds 32, 33,45 166,44 and 167.61 Halogens can be reductively removed from [l,2,3]triazolo-[4,5-6]pyridines 160,146 168,220 and 169,142 and from pentachloro derivative 164, giving dichloro compound 170.208 Removal of thiol groups by reduction... 

Deoxygenation of pyridine N-oxides. This reaction can be carried out with P214 in refluxing CH2C12 in 10-30 minutes with yields of 80- 95%. 

Deoxygenation. Hexachlorodisilane is useful for deoxygenation of nitrones and various N-oxides in good yields under exceptionally mild conditions (25° or below).1 It is recommended for deoxygenation of 2,3-disubstitutcd quinoxaline 1,4-dioxides under mild conditions yet at reasonable rates.2... 

Deoxygenation of N-oxides reduction of ArNO2. An Mo(IIl) species obtained by reduction of MoC15 with zinc in aqueous THF reduces aromatic N-oxides in 45 65% yield. The reagent also reduces aromatic and heteroaromatic nitro compounds lo amines in 30-70% yield. 

Deoxygenation of N-oxides,4 TiCl4 -NaBH4 (1 2) in DME reduces the N-oxide of pyridine and mcthylpyridines (picolines) to the corresponding heterocycles in high yield. However the N-oxide of quinolines and isoquinolines is reduced further to dihydro derivatives of the hetcrocyclcs. Pyridine, quinoline, and isoquinoline themselves are not reduced by this low-valent titanium species. Reduction of heterocyclic N-oxides with TiCI, has been reported (6, 588). 

R = Ar,R2 = H), which were deoxygenated in one instance.19 Other N-oxides (133 R1 = Ar,R2 = H and R1 = R2 = Ph) were obtained directly by hydrazinolysis of the 4-chloropyridine 131b.126 Reaction of hydrazine with the pyridinium salt 134 caused replacement of the methoxy group with formation of 135 29 and, more unexpectedly, 3-carbethoxy-4-pyrrolylpyridine (136) and hydrazine afforded an almost quantitative yield of 137 by expulsion of the pyrrole nucleus.130... 

Chemical reduction of azine //-oxides, depending on substrate structure, reductant and reaction conditions can proceed both with or without deoxygenation of the N-atom. Thus, 1,2,3-triazine 1-oxide (337) with NaBH4 gives 2,5-dihydro-1,2,3-triazine (336), suggesting that the N-oxide moiety back-donates electrons to the triazine ring. On the other hand, on reduction of the isomeric 2-oxide leading to tetrahydro derivatives (338) and (339) the N-oxide function is not touched (82H(17)317). 

Photolysis of pyridazine N-oxide and alkylated pyridazine iV-oxides results in deoxygenation. When this is carried out in the presence of aromatic or methylated aromatic solvents or cyclohexane, the corresponding phenols, hydroxymethyl derivatives or cyclohexanol are formed in addition to pyridazines. In the presence of cyclohexene, cyclohexene oxide and cyclohexanone are generated. 

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