Solvent effects in deamination reactions

Abstract
Nitrous acid deaminations of (S)‐2‐butanamine, (2R,3S)‐3‐methyl‐2‐pentanamine (8), cyclopropananmine (17) and 4,4‐dimethyl‐2‐adamantanamine (30) have been studied in water and in a series of carboxylic acids of decreasing polarity (acetic, 3,3‐dimethylbutyric, 2‐ethylhexanoic acid). The stereochemistry of aqueous deaminations varies from predominant inversion to predominant retention, depending upon the structure of the substrate (steric hindrance, neighbouring‐group participation, etc.). In carboxylic acid media, alcohols arise with predominant retention, i.e. by front‐side attack of the “internal” nucleophile (water). Inverting displacement of nitrogen by the “external” nucleophile (carboxylic acid/carboxylate) increases with decreasing polarity of the solvent. Even cyclopropanamine yields cyclopropyl esters (2‐10%) of inverted configuration, as shown with the aid of deuterium labels. Current mechanistic concepts are modified to account for these results.

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