Carbinolamines, pseudobasic

III. Structure and Mechanism of Formation of Derivatives of the Heterocyclic Pseudobasic Carbinolamines... 

The heterocyclic pseudobasic carbinolamines show a very varied reactivity. However, the structure of a large number of their transformation products, in particular those from which conclusions have been drawn as to the structure of the initial pseudo base, are incorrect even in the most recent literature. 

The study of the enamine structure may be associated, to a certain degree, with the problem of the so-called pseudobases an instructive, but somewhat specialized, review of these compounds was contributed by the late Professor Beke 47 to the first volume of this series. The name pseudobases was given by Hantzsch,48 towards the end of the last century, to those a-aminocarbinols which undergo a structural change during salt formation and yield salts with the loss of one molecule of water. The liberation of pseudobases from their salts is accompanied by rehydration. This behavior has been observed with a,/3-unsaturated heterocyclic compounds and, to a certain degree, with aromatic heterocyclic pyridine derivatives. As formulated by Gadamer,49 the pseudobases represent a potential tautomeric system of three components, the quaternary hydroxide A, the carbinolamine B, and the open-chain amino-carbonyl derivative C, in which all three components exist in a mobile equilibrium ... 

The behavior of the 1 -methiodide (179) is more difficult to explain as its spectrum in alcohol is nearly identical to that in alkaline solution, and these both show the same pattern as the 2-methylene indoline, i.e., with an intensified band II and a band III shifted to the red as compared to its methiodide. It seems possible that these compounds exist as the carbinolamine, or pseudobase, in hydroxylic solvents and are in tautomeric equilibrium (179 181). The direction of this equilibrium has been attributed by Beke to the basicity of the nitrogen, as well as other factors. B14ha and Cervinka discuss the importance of steric and polar structural factors, citing examples of stable pyrrolidine pseudobases. Indeed, Ficken and Kendall isolated the 4-azaindoline pseudobase (123), characterizing it by analysis and infrared spectral evidence. They similarly characterized the 2-methylene base (121), and it is unfortunate that their ultraviolet spectra were not determined. The 2-methylene-7-azaindoline... 

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]. 

The ease of formation of pseudobases (carbinolamines) from a variety of isoquinolinium salts has been investigated. Increasing pH facilitates pseudobase formation. Nitidine forms a pseudobase more readily than berberine, while 6,7-dimethoxy-2-methylisoquinoline did not form a pseudobase even at pH 13.2 Sanguinarine and chelerythrine acetates exist in an equilibrium mix-... 

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