Dimethyl malonate → O-Methylisourea

Participants

Reaction Steps

One method taught in the art for making the 2-methoxy analog of DHEP is disclosed by S. Basterfield and E. C. Powell in Canadian Journal of Research, vol. 1, pp. 261-272 (1929). In this article, Basterfield and Powell describe the synthesis of a number of 2-alkoxypyrimidine derivatives, including 2-methoxy-4,6-dihydroxypyrimidine (DHMP). DHMP is prepared by condensing O-methylisourea with dimethyl malonate. Although a 75% of theoretical yield is reported in the article, the theoretical yield requires consumption of 2 equivalents of O-methylisourea to form 1 equivalent of the O-methylisourea salt of DHMP. Thus, the reported 75% yield means that 0.75 moles of DHMP salt are formed for every 2 moles of O-methylisourea utilized. The O-methylisourea is prepared by first preparing and isolating the hydrochloride salt of O-methylisourea, then neutralizing this salt with potassium hydroxide in ether to form neutral O-methylisourea, which is apparently isolated as well. At page 262 of their article, Basterfield and Powell reference the unpublished observations of Stieglitz and Basterfield, who found that O-ethylisourea can be condensed with dimethyl malonate in the absence of a base and of a solvent to obtain the O-ethylisourea salt of 2-ethoxybarbituric acid, i.e., a salt of DHEP.

Provenance & Evidence