Condensation reactions of malonyl chloride with nitriles

• Main Author: Zaidi, Saiyid Mohammad Naseer Alam
• Published: Imperial College London 1967
• Subjects: 547
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.622998

The study of some condensation reactions of malonyl chloride with nitriles revealed some very interesting results. It was found that fluoroacetonitrile reacted with malonyl chloride in the molar ratio of 2:1 and yielded 4-chloro-2-fluoromethy1-6-hydroxypyrimidine (65%). The reaction of malonyl chloride with chloroacetonitrile produced mainly 2-chloromethyl-4-chloro-6-hydroxy-pyrimidine along with some 2,3-dichloro-4,6-dihydroxy-pyridine. In contrast, like fluoroacetonitrile acetonitrile, bromoacetonitrile and a-bromopropio nitrile with malonyl chloride yielded exclusively their corresponding pyrimidines. The structures of these pyrimidines and pyridines were established with the aid of nuclear magnetic resonance, mass spectrometry, infrared and ultraviolet light absorption spectroscopy. Their structures were also confirmed by chemical transformations. The formation of RCOC1 along with the pyrimidines has been established by nuclear magnetic resonance,isolation of a characteristic derivative, and gas-liquid chromatography. The possible mechanisms of this new synthesis of pyrimidines have been discussed. In seeking evidence, some syntheses were performed with malonyl chloride labelled with carbon-14. The results of these experiments with labelled malonyl chloride and with halogenomalonyl chlorides showed that all the three carbon atoms of malonyl chloride appeared in the pyrimidine nucleus whilst all of the carbon atoms of the RCOC1 product belonged originally to the starting nitrile. An interesting feature of this new synthesis of pyrimidines is that it is the first direct synthesis of chloro-pyrimidines in which halogen appears at an active position of the ring.