Pseudobases oxidation

In some cases two isomeric tropones (4-oxo and 6-oxo) and two or more tropilidenes are formed from tropylium salts [66JCS(C)926] or from the equivalent pseudobases (cycloheptatrienols or tropols 69ZOB2601). Finally nucleophilic attack can generate an unstable tropol that yields, on oxidation, the desired tropone (78AJC1607). 

An example of disproportionation to (109) and (110) is provided by the behaviour of the berberinium ion in alkaline solution (Scheme 62). The pseudobase of the 5-methyl-phenanthridinium cation is present even in neutral solution (equation 85). Attack at position 9 in acridinium salts is also very easy, and they rearrange to pseudobases in a few minutes in alkaline solution. These pseudobases, unlike the others described, do not undergo ring opening. They readily disproportionate or are oxidized to acridin-9-ones by air when the starting salt is unsubstituted at C-9 (B-78MI20502). Pyridine 1-oxides and their analogues... 

Stevens et al. (58JCS3067) found that when quinolizinium iodide was treated with silver oxide, or when it was warmed with ION NaOH, there was no evidence of the C-hydroxyla-tion (pseudobase formation) that is characteristic of the methiodides of the azanaphthalenes. Their suggestion that this resistance of the quinolizinium ion is understandable, in that C-hydroxylation would destroy the aromaticity of both rings, is probably correct. 

The C-hydroxylation of benzoquinolizinium ions is easier and, although the position of the attack on benzo[a]quinolizinium (2) salts is not known, it has been demonstrated (67JOC733) that hydroxylation of the acridizinium (benzo[6]quinolizinium, 3) ion must occur at position 6 (Scheme 8). It was not possible to obtain a pure sample of the pseudobase (17) or the 2-(2-formylbenzyl)pyridine (18) in equilibrium with it, but oxidation of the mixture with ferricyanide afforded a small amount of benzo[Z>]quinolizinone (19) (62CI(L)1292), while reaction with hydroxylamine afforded a good yield of 2-(2.-pyridyl-methyl)benzaldoxime (20) (67JOC733). 

This theory agrees with the later results of van Tamelen and Baran (58JA4659), who were able to get N-benzylcytisin (43) from the bicyclo-substituted pyridinium salt 42 via Decker oxidation. Since formation of an anhydro base 45 is violated according to Bredt s rule, an equilibrium between 44 and a C-6 pseudobase can exist, the latter being dehydrated to yield 43 (Scheme 9). 

This result confirmed the mechanistic interpretation of the Decker oxidation suggested by Abramovith (71 JCS(B) 131). The intermediate complex 57 is oxidized to 48, which implies the introduction of the pyridone carbonyl function into the originally substituted C-2 position of the heterocycle (Scheme 12). These results have also been confirmed by Nesvadba and Kuthan (83CCC511). With increasing concentration of alkali, a C-6 pseudobase is... 

According to the ratios of 48 and 61, the competition of two pathways can be formulated (1) oxidative elimination of the 2-substituent (- 48) and (2) dehydration of C-6 pseudobases (- 61). Therefore, an increasing degree of substitution of the 2-a-carbon atom decreases the formation of 48. 

Oxidation of the enamine 74 via the anion of enolamine 75 yields 76 which cannot be formed from 77 in alkaline medium. Cleavage of 76 according to Abramovitch s hypothesis is the last step of the reaction. If formation of the enolamine is prevented by alkylation of the 2-a-methylene group as in 78, oxidation of the pseudobase 79 in equilibrium with the enamine structure leads to the formation of 80-82. In addition, C-6 pseudobases are dehydrated to give 83 (86ZN(B)655) (Scheme 17). 

However, it was observed that if one of the ortho C-H groups in the 1-aryl ring of 122 was absent, then only monocyclization occurred (80JCS(P1)1879). Large specific effects of traces of water on the C- and H-NMR spectra and UV spectra of 124 have been attributed to pseudobase formation, but attempts to trap a pseudobase by Decker oxidation to the oxo form were unsuccessful (830MR649). 

In all cases, the cations display spectral changes consistent with pseudobase formation at electronic spectral concentrations, with the disproportionation reaction becoming important at much higher concentrations of the heterocycle. This concentration dependence indicates the bimolecular nature of these reactions, and the 1 1 ratio of oxidized and reduced products, in those cases which have been carefully investigated, is indicative of a true disproportionation reaction. A particularly interesting case is the report217 of equimolar amounts of dihydropyridines (a mixture of 125 — 127) and pyridinones (a mixture of 128 and 129) from the reaction of the l-methyl-3-cyanopyridinium cation in aqueous base. The 1 1 ratio of oxidized and reduced products is sometimes obscured by subsequent air oxidation of the reduced product to the oxidized product. 

Pseudobases have often been postulated as intermediates in the chemiluminescent oxidation of acridinium cations to acridinones.103-297 299 Both the mono- and dipseudobases (156 and 157) of lucigenin have been proposed as intermediates in the chemiluminescent oxidation of this cation in basic solutions. 

Meso-ionic compounds N-Oxides Pseudobases Reissert compounds... 

A-Methylpyridinium or A-methylquinolinium salts [246] may be oxidized to the N-methyl-2-pyridone or A-methyl-2-quinolone, respectively, in alkaline medium containing some potassium hexacyanoferrate (III). The reaction is probably an indirect electrolysis in which the hexacyanoferrate oxidizes the pseudobase and is, in turn, reoxidized at the anode. 

In the case of azapetine (12) and nicotine (13), the iminium ion intermediate rather than the carbinolamine appears to be the form of substrate preferred by aldehyde oxidase [63-66]. On the other hand, the ring-opened aldehyde intermediate (aldophosphamide) (14) of cyclophosphamide is oxidized by the enzyme [67], although the isomeric 4-hydroxycyclophos-phamide (15) also undergoes oxidation by a soluble fraction enzyme [11]. Oxidation of the carbinolamine form to a cyclic lactam would not seem to involve nucleophilic enzyme attack, and yet we have shown that the stable pseudobase of 3-methylquinazolin-2-one (16), is an efficient substrate of aldehyde oxidase and competitively inhibits the oxidation of both quaternary and non-quatemized substrates [62]. 

A -Alkylpyridinium ions add hydroxide ions reversibly and exclusively in the 2-position, forming 2-hydroxy-l,2-dihydro-iV-alkylpyridines ( pseudobases , e.g. 43) which can be oxidized by mild oxidizing agents to A-alkyl-2-pyridones, e.g. 44 ... 

Although acridinium esters can be used to determine hydrogen peroxide, they are more commonly used as labels for immunoassay or DNA probes. As no catalyst is required, acridinium ester chemiluminescence has a lower chemical blank than the oxidation of luminol and therefore has superior detection limits. A strongly alkaline solution (pH 12-13) is required, but under these conditions acridinium esters undergo reversible conversion to the non-chemiluminescent pseudobase form (Scheme 1), which slowly decomposes. As a consequence, acidic hydrogen peroxide is added to reconvert the pseudobase to the acridinium ester before the chemiluminescence reaction is initiated with a sodium hydroxide solution. 

Isoquinolinium salts can be readily converted to isoquinolones through air oxidation of the corresponding pseudobases. ... 

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