Formation of 3,4-dihydro-2-hydroxy-4-ureidopyrimidine from malonaldehyde and urea.

Abstract

Malonaldehyde is produced by the oxidation of highly unsaturated fatty acids.1) Urea is one of the common components in animal tissues. Hamberg et aP) isolated 2-hydroxypyrimidine from tissue homogenates to which was added malonaldehyde. This observation suggests a possibility that malonaldehyde produced from highly unsaturated fatty acids reacts with urea to form N-containing heterocyclics in a wide variety of foods. Dornow and PeterIein3) obtained a heterocyclic compound (C.HsN 40 Z) in 77 % yield by the reaction of 3-ethoxyacrolein acetal, a precursor of malonaldehyde, with urea. Kobayashi ) also obtained the same product, propane diurea, in 34 ~~ yield from 1,1,3,3-tetramethoxypropane and urea. The structure of this compound has been considered to be either 3,4-dihydro-2-hydroxy-4-ureidopyrimidine (1) or 2,4,6,8-tetraazabicyclo[3,3,llnona-3,7-dione (II), but it has not been determined. The present study was undertaken to elucidate this structural problem. From the IR and MS spectra, and by the identification of the hydrolysis product, the heterocyclic compound obtained by the reaction of malonaldehyde with urea was determined to be 3,4-dihydro-2-hydroxy-4ureidopyrimidine (1). Compound I had mp, 31O~ 15°C (decomp.) and the molecular formula, CHsN 40 Z, which agreed well with those reported in the above-mentioned literatures. The IR-absorption bands characteristic of primary amide were found at 3250 (~N-H), 1650 (vC~O) and 1640 cm1 (oN-H); m/e 156 (M+) and m/e 97 (base peak, M+ 59 (NH-CO-NHz» were observed in the MS-spectrum. On the acid-hydrolysis of I in hydrochloric acid or nitric acid aqueous solution, one molecule of urea was eliminated from I and 2(IH)pyrimidinone (III) was obtained in a yield of 41 % and 32 %, respectively. The chemical structure of III was confirmed by elementary analysis and its IR, UV, MS and NMR spectra. On the basis of the above data, the heterocyclic compound obtained from malonaldehyde and urea was found to be 3,4-dihydro-2-hydroxy-4-ureidopyrimidine (formula (D). Agric. Bal. Chern., 42 (1),171--172,1978