A novel synthesis of 5-hydroxycotinine has provided a homogenous product which has been examined spectroscopically in order to assess the possible equilibrium of the hydroxy lactam with the tautomeric keto amide structure originally proposed for this urinary metabolite of the tobacco alkaloid nicotine. Treatment of the readily available (S)-3,3-dibromocotinine with methanolic KOH led to (fi^S)-l-methyl-5-(3'-pyridyl)-5-methoxypyrrolin-2-one which upon cleavage of the enol ether and catalytic hydrogenation of the double bond provided the desired product as the pure crystalline hydroxy lactam. The equilibrium of the hydroxy lactam with the ring-open keto amide tautomer was examined by NMR and was shown to proceed slowly in deuteriochloroform and rapidly in water.

No abstract

Aus dem (S)‐3,3‐Dibrom‐cotinin (I) erhält man in der angegebenen Weise über (II) und (III) das 5‐Hydroxy‐cotinin (IV), das ein Metabolit des Tabak‐ Alkaloids Nicotin ist.

Das Thiophenol (I) reagiert mit den Dibrompropylaminen (II) in Aceton in Ausbeuten von 10% zu den 2‐Aminomethylbenzoxathianen (III).