Reaction Of The Photoxidation Of Thiazine Ring In Promethazine

Comparative studies in aqueous solutions47 showed that aminopyrine is the most reactive derivative,45 and in general 4-amino substituted pyrazolones react faster than 4-alkyl48> 49 derivatives. In the presence of oxygen, photolysis is accompanied by a photo-oxidation reaction.50 The above order of photoreactivity for pyrazolones remains the same in the solid state.51 However, in the latter case different processes may be involved, as with aminopyrine for which the main reaction in the solid is type I (i.e. involving addition of ground state oxygen to a radical) photo-oxidation of the methyl group in position 5. This has been attributed to the small distance between the methyl group of one molecule and the carbonyl group of a neighbouring molecule in the lattice. This makes hydrogen abstraction easy and the resulting radical (31) adds oxygen to finally yield (32) (Scheme 13).52

Ph hv » C4H9-CHCON—NHPh + C4H9—CHCON —NHPh H2O I | I

Scheme 14

Ph y_^c4H9

Promethazine Molecules

Azapropazone (apazone, 33), a fused pyrazole derivative, undergoes cleavage of the five-membered ring to give a benzotriazine (34) by irradiation in methanol; the product then undergoes jV-dealkylation to give (35). In the solid state a different process, 1,3-sigmatropic migration of one of the acyl groups, occurs and leads to isomeric (36) (Scheme 15).53

2.1.3 Immunosuppresant and Anti-histaminic Drugs. The immunosuppressant drug azathioprine (37) undergoes fragmentation of the C-S bond to give 6-mercaptopurine (38) and l-methyl-4-nitro-5-hydroxyimidazole (39) as well as a cyclisation reaction suggested to give (40) (Scheme 16).54 Among drugs with anti-histaminic action, terfenadine (41) undergoes oxidation (main process) and dehydration at the benzylic position, to give products (42) and (43) respectively, upon irradiation in aqueous solution (Scheme 17),55 and diphenylhydramine (44) suffers progressive iV-dealkylation.56 The thiazine derivative promethazine (45) is N-dealkylated to phenothiazine (46) and this in turn oxidised to the sulfone (47) and to 3//-phenothiazin-3 -one (48) (Scheme 18).57

Ph2CHO(CH2)2NMe2 (44)

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