Mechanistic aspects of the bromination of 10‐substituted phenothiazines

The addition of 1 and 2 molar equivalents of bromine to a series of 10‐alkylphenothiazines, 1a‐d (methyl, ethyl, n ‐propyl, and isopropyl, respectively), yields the corresponding 3‐bromo‐ and 3,7‐dibromo‐10‐alkylphenothiazines ( 11a‐d and 12a‐d , respectively). Evidence which supports the typical clectrophilic aromatic substitution mechanism is presented. Radical cations ( 12a‐d .+ ) arc produced when 12a‐d are treated with 1 or 2 molar equivalents of bromine. Upon boiling in acetic acid these radical cations are converted predominantly to 1,3,7,9‐lelrabromophenothiazine ( 5 ) and the parent 3,7‐dibromo‐10‐alkylphenothiazine ( 12a‐d ) with the evolution of hydrogen bromide. The 10‐methyl radical ( 12a ) gives, in addition, 1,3,7‐tribromo‐10‐methylphenothiazine ( 15 ). A mechanism if proposed for these reactions in which initial dealkylution of 12b‐d .+ to 3.7‐dibromophenothiazine radical cation ( 13 ) occurs followed by reduction of 13 .+ by bromide ion to parent 3,7‐dibromophenothiazine ( 13 ). Subsequent bromination of 13 by molecular bromine produced in the previous redox reaction yields 1,3,7‐tribromo‐( 14 ) and 1,3,7,9‐tetra‐bromo‐( 5 ) phenothiazines. The small size of the methyl group allows 12a to be brominated at the 1‐position prior to dealkylation. In addition to undergoing bromination at the 3‐ and 7‐position, 10‐isopropylphenothiazine ( 1d ) is oxidized to the radical cation 12e .+ when treated with bromine. 10‐Benzylphenothiazine ( 1e ), however, undergoes oxidation to radical cation 1e .+ exclusively. This radical cation debenzylates readily at room temperature and is converted finally into phenothiazine.