Unusual Reaction of Alkaloid Cotarnine with 1,3-Dimethylbarbituric Acid

Abstract

Cotarnine is a natural pseudobase of the isoquinoline series, which is capable of undergoing ring3chain transformations [1]. Its structure may be represented as two isomeric forms occurring in equilibrium: bicyclic Ia and monocyclic Ib [2]. Monocyclic isomer Ib is responsible for formation of derivatives at the aldehyde (e.g., oxime [3]) or amino group (amides [4]). In the other cases cotarnine behaves as cyclic semiaminal Ia, which is readily dehydrated to give iminium ion, and reacts with some CH and NH acids following the Mannich reaction pattern and yielding the corresponding tetrahydroisoquinoline bases [2, 5, 6]. The reaction of cotarnine with 1,3-dimethylbarbituric acid (II) on heating in chloroform leads to formation of 6-hydroxy-1,3-dimethyl-5-(4-methoxy-6methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione (III) as inner salt [7]. When the same reaction was performed with 2 equiv of barbituric acid II under more severe conditions, we isolated an unusual product, spiropyrimidine derivative IV (Scheme 1). The structure of IV was derived from the data of mass spectrometry and NMR spectroscopy (H and C; the spectra were recorded in a standard mode and also using COSY, DEPT, and INADEQUATE techniques). Presumably, elevated temperature favors formation of cotarnine tautomer Ib which react with 1,3-dimethylbarbituric acid (II) to give adduct V. Such products are typical of reactions of barbituric acids with aromatic aldehydes [8]. Compound IV is likely