Radiochemical studies of hydrogen exchange in organic compounds

Abstract

A property of a new or unknown organic compound which must be determined once the empirical formula and molecular weight are known, is the number of active or replaceable hydrogen atoms which the compound contains. These include hydrogen atoms present in amine, hydroxyl, carboxyl and other groups, where the hydrogen is not bound to a carbon atom but to an oxygen, nitrogen or sulphur atom or is in a position where it can ionize. The most general method by which this may be done quantitatively, is the one originally due to Zerewitinoff Zerewitinoff - Berichte 40 2023 (1907) 41 2233 (1908) 42 4802 (1909) 43 3590 (1910) 47 1659 (1914) 47 2417 (1914) and since developed on a micro scale by Roth A. Soltys Mikrochemie 20 107 (1936), Flaschentrager A. Roth Mikrochemie 11 140 (1932), whose method incorporates work by Tschugaeff - Flaschentrager z. Physiol Chem. 146 219 (1923) and the other two authors, and Soltys L. Tschugaeff Berichte 35 3912 (1902), and incorporates many of the latest improvements. This involves the quantatatively evolution of methane from reaction of the Grignard reagent MeMgI on groups such as -SH, -OH, -NH2, -COOH etc., i.e. those groups containing active or replaceable hydrogen atoms. Analysis by this method requires extreme care in technique and exact attention to experimental details. High results are obtained if the solvent or any part of the apparatus contains moisture and the whole determination must be carried out in an atmosphere of nitrogen to avoid reaction of the Grignard reagent with any oxygen present. Low results are obtained if the test solution does not dissolve completely in the chosen solvent and it is essential to carry out a blank prior to each analysis. The proceedure is labourious and painstaking and gives an accuracy of not greater than 5% using 3-5 mgm of organic compound. It also has the disadvantage that the Grignard Reagent will also react with other groups, such as carbonyl, aldehyde, nitrile etc., which may be present. This method cannot be applied to highly water soluble compounds which do not dissolve in ethers or other organic solvents and as the molecular size or complexity of the sample increases, the accuracy of the gasometric reactions becomes less, due to side reactions and incomplete reaction.