Gas chromatographic alkylation studies of phenytoin, mephenytoin and primidone: Investigation of butylated derivatives

Abstract 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 1 H NMR and 13 C NMR. With the acetone—butyl iodide—silver oxide method the main derivatives were O -butylated compounds. The other methods yielded predominantly N -butylated derivatives.