The on column methylation of clonidine and p-hydroxyclonidine with trimethylanilinium hydroxide

The structures of the methylated clonidine derivatives formed by on column methylation with trimethylanilinium hydroxide are revised. The almost exclusive formation of derivatives of phenylimino-N,N-dimethylimidazolidine structure is explained in terms of a fast kinetically controlled reaction of substrate anions. The reliability of a stable isotope dilution assay for clonidine is discussed in view of these results.