Lichtinduzierte Fragmentierungen des D‐(−)‐Methadon‐Hydrochlorids in wäßriger Lösung

Abstract

Unter Lichteinwirkung werden warige D(-)-Methadon-Hydrochlorid-Losungen weitgehend zersetzt. Radikalische a-Spaltung, y-Wasscrstoff-Abstraktion und eine Photocyclisierungdie zum 3,3-Diphenyl-2-athyliden-S-methyltetrahydrofuran f h r tkonnten als primLe Abbaumechanismen wahrscheinlich gemacht werden. Die auf diesen Wegen entstandenen Photoprodukte sind zum Teil selbst instabil und fragmentienn in Formaldehyd, Acetaldehyd, Glyoxal, Aceton, Methylglyoxal, Brenztraubedure, Benzophenon, Benzpinakon und Benzaldehyd. Fragmentation of D-(-)-Methadone Hydrochloride by Light Under the influence of light, aqueous solutions of D-(-)-methadone hydrochloride undergo de-composition to a great extent. Radical a-cleavage, 7-hydrogen-abstraction and photocyclisation leading to 3,3dipheny1-2ethylidene-S-methyltetrahydrofuranhave been shown to be pmbable primary degradation mechanisms. Some of the photoproducts formed are unstable and undergo fragmentation to formaldehyde, acetaldehyde, glyoxal, acetone, methylglyoxal, pyruvic acid, benzophenone, bcnzpinacone and benzaldehyde. 7 R. M. Noyes, C. Porter u. J. E. Jolly, Chem. Reviews 56, 4 9 (1956). 8 J. N. Pitts jr., J. chem. Educat. 34, 112 (1957). 9 M. Hesse, Helv. chim. Acta 50, 42 (1967).u. friihere Mitt. dieser Reihe. * Das MS vom 3-HCI (200", Direkt-EinlaO) gibt keinen Hinweis auf thermisch entstandenes 1. Ein Ion MZ 264 z.B. fehlt vollig. 10 D.

Photochemistry of drugs: An overview and practical problems

“…5-Aminosalicylic acid (26), used for the treatment of The narcotic analgesic methadone hydrochloride (27) reacts when irradiated by UV light both in aqueous solution41 and in the solid state. 42 The processes observed (fragmentation and cyclisation, see Scheme 12) are a typical manifestation of the radical-like character of the nx* state of ketones (a-and j3-cleavage, see Scheme 1, a). However, this drug is photostable in an isotonic solution when exposed to ambient light.43 9 EtCOCPbCH2CHCH3 hv*EtCHO + PbC=CHCHCH3 + I NMe2 CH3C…”

“…The immunosuppressant drug azathioprine (37) undergoes fiagmentation of the C-S bond to give 6-mercaptopurine (38) and l-methyl-4-Ntro-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 N-dealkylation. 56 The thiazine derivative promethazine (45) is N-dealkylated to phenothiazine (46) and this in turn oxidised to the sulfone (47) and to 3H-phenothiazin-3-one (48) 2.…”