The elucidation of the mass spectral fragmentation pathway of α‐methyldopamine derivatives by chlorine labeling

The mass spectra of the tristrifluoroacetyl derivative of α-methyldopamine and the bistrifluoroacetyl derivative of 3-O-methyl-α-methyldopamine contain important ions which can be rationalized by two alternative fragmentation pathways. These ambiguities were resolved by means of a simple chemical derivatization technique. The labile phenolic ester groups were hydrolyzed and subsequently re-esterified by reaction with chlorodifluoroacetic anhydride in the presence of ethyl acetate thereby labeling ions containing ester group(s) in the mass spectra with the diagnostic chlorine isotope ratio. This resulted in the addition of 16/18 mass units to the weights of the ions for each fluorine atom replaced by chlorine. Since it was easy to distinguish loss of the mass of a neutral molecule of trifluoroacetamide (113 mass units) from the ions of a chlorodifluoroacetoxy radical (129 mass units), the elimination of trifluoroacetamide was distinguished from that of trifluoroacetoxy radical. Derivatives were also prepared in which the chlorine label was located on the N-acyl function. The mass spectra of the chlorine labeled compounds showed that the major fragmentation pathway of tristrihaloacetyl-α-methyldopamine and bistrihaloacyl-3-O-methyl-α-methyldopamine is by loss of a neutral molecule of trihaloacetamide.