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The alkylation of phenytoin, mephenytoin and primidone with n-alkyl iodides in N,N-dimethylacetamide with tetramethylammonium hydroxide was investigated by gas chromatography. With methyl iodide phenytoin and mephenytoin were each converted into a single derivative; the use of other alkyl iodides yielded more than one product. Primidone was converted with methyl iodide and butyl iodide into a major derivative (> 90%) and a minor one. Butylation of the compounds by this method was compared with butylation in an acetone-butyl iodide mixture with potassium carbonate, caesium carbonate or silver oxide added, and with on-column butylation. All these methods resulted in the production of more than one derivative. The derivatives were identified by mass spectrometry and by 1H NMR and 13C NMR. With the acetone-butyl iodide-silver oxide method the main derivatives were O-butylated compounds. The other methods yielded predominantly N-butylated derivatives.

Methods of analysis of the anticancer drug hexamethylmelamine, its physicochemical properties, its therapeutic uses and its fate in vivo upon oral administration, are described. The data are taken in part from the literature, in part from our own studies. The low solubility of hexamethylmelamine in water has prevented the parenteral administration of the drug to humans. The preparation of the water-soluble monohydrochloride of hexamethylmelamine, which may be suitable for this purpose, is reported, as well as its physicochemical characteristics and methods of analysis.