697. Organic reactions in aqueous solution at room temperature. Part I. The influence of pH on condensations involving the linking of carbon to nitrogen and of carbon to carbon

Abstract

The object of this series of papers is to broaden the field initiated by Robinson and Schopf and usually termed "syntheses under physiological (or ''cell-possible'') conditions," in relation to both biochemical problems and general organic synthetic methods. Extensive (rather than intensive) investigations have shown that water at room temp, is an effective medium for some very simple condensations involving substances containing the naturally-occurring groups CHO, CO, NH2, CO.NH2, NH2.C:NH, CH2.CN, CH2.CO, CO.CH2.CO, CO.CH2.CH2.CO(andH.CO2H), leading to well known examples of Schiff bases, and quinoxallne, diazepine, pyrimidine glyoxaline, pyrrole, and pyridine derivatives. Some failures have suggested that in this type of work a methylene group requires activation from both sides for successful condensation. In two cases of Claisen-Knoevenagel condensations, glycine has been shown to be a useful catalyst. As found by Schopf in other cases, variation of the pH has striking effects on the yields. Our reaction conditions differed from those used by Robinson and Schopf in that, while they usually had to isolate their products from soln., we chose water-soluble reactants which produced very insoluble products. A considerable part of the driving force for the reactions is therefore the displacement of equilibria by precipitation. The products in most cases are obtained in reasonable, and sometimes very high, yields after a reaction time of a few days, and are isolated pure direct from the reaction mixture, the usual losses thus being eliminated. Several of the reactions may have preparative value, or may serve for future kinetic investigations. Some of the exptl. results support the theory that some reactions, normally considered to be base-catalysed, may also take place under acid-catalysis.