Pseudobases, disproportionation

There are a number of claims4 40 51,69,150,247,268-274 for the isolation of bimolecular ethers from various other heterocyclic cations although the structures of these products have rarely been unambiguously established. The reaction mechanism outlined for the formation of 114 probably does occur in other heterocyclic systems, particularly in those cases in which alkoxide ion formation from the pseudobase readily occurs. Solubility considerations may dictate the precipitation of the bimolecular ether rather than the pseudobase from basic aqueous solutions containing relatively high concentrations of the heterocycle. However, such bimolecular ether formation will usually be in direct competition with the pseudobase disproportionation reaction (Section V,D) which shows the same pH dependence. 

Habermehl and Schunk289 have drawn attention to the analogy between the pseudobase disproportionation and the Cannizzarro reaction of aldehydes, which can be considered to be a disproportionation of the aldehyde hydrate to a carboxylic acid and alcohol. This reaction is usually considered to involve hydride transfer from either the mono- or dianion (i.e., 143 or 144) of the aldehyde hydrate to the carbonyl group of another aldehyde molecule. The anions 143 and 144 are clearly quite similar electronically... 

This dimeric formulation also accounts for the thermal disproportionation of the compound into a mixture of 2-methyl-l,2,3,4-tetrahydro-jS-carbohne and 2-methyl-jS-carboline anhydro-base. Normal pseudobase formation (453 R = CHs ) takes place in the case of 9-methyl-3,4-dihydro-j3-carbohne methiodide (452 R = CHg). Neither the dimeric anhydro-base nor the -methyl pseudo-base undergo a base-catalyzed disproportionation reaction to give the 1,2,3,4-tetrahydro-and the l-oxo-l,2,3,4-tetrahydro-jS-carboline in a manner analogous... 

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... 

It is well known that disproportionation of 154 occurs via direct hydride ion transfer from the 9-position of the pseudobase 155 to the 9-position of the acridinium ion, to form acridone 156 and acridan 157 (77JCS(P1)1966 84JCS(P2)661) (Scheme 26). 

Pseudo-bases derived from 2-unsubstituted 1,3-dialkylperimidinium salts disproportionate into 1,3-dialkylperimidones and l,3-dialkyl-2,3-dihydroperimidines, the former always predominate. By contrast, l-aroyl-3-alkylperimidinium salts (203), formed in situ from l-/ -perimidines and aroyl chlorides, produce pseudobases (204) which exist exclusively in the acyclic form (205). Interestingly, heating with alkali cleanly converted (205) into the corresponding 1,2-disubstituted perimidines (206). This reaction is of preparative significance for the introduction of aryl and heteroaryl groups in position 2 of perimidines (81RCR1559). 

Treatment of a quaternary salt (14) with concentrated alkali causes disproportionation to occur to yield an isocarbostyril (13) and a 1,2-dihydroisoquinoline (6).25 The reaction, which probably proceeds via the pseudobase (15), has been used26 in a modified berbine ring... 

Other cationic rings. Diazinium salts resemble pyridinium salts in their behavior. They form pseudobases with hydroxide ions which can disproportionate (e.g., 2-methylphthalazinium ion 217 2-methylphthalazin-l-one + 2-methyl-1,2-dihydrophthalazine) or undergo ring fission (e.g., 3-methylquinazolinium ion 218). 2-Alkyl-1,2,3-triazinium salts add nucleophiles at C(5) <2003S413>. 

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. 

This interpretation of the mechanism of disproportionation is supported by two observations on crossed disproportionation reactions. In a kinetic study285 of the reduction of the 2-methylisoquinolinium cation by a series of2-benzyl-5-nitroisoquinolinium cations, the pH dependence of the reaction was observed to be consistent with hydride transfer from the pseudobase alkoxide ion 133 to the 2-methylisoquinolinium cation. Clark and Parvizi111... 

The other three derivatives were minor side-products. (HI) 6-Hydroxy-dihydrosanguinarine (34), a pseudobase, was a product of the spontaneous hydrolysis of the aminoacetal 33 by residual water in the CDCI3. (IV) Oxosanguinarine (35) and (V) dihydrosanguinaiine (36) were the products of the disproportionation of the pseudobase (Scheme 5). 

The heterocyclic rings of (benzo)pyridazine systems are electron deficient and thus susceptible to attack by nucleophiles. However, in the absence of a suitable leaving group this is usually unfavoured due to loss of aromaticity. For example, covalent hydration is not observed, though pseudobase formation can occur with subsequent disproportionation to give, for example, phthalazinones and dihy drophthalazines. 

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