A. 2-Thio-6-methyluracil. In a 2-l. flask are placed 76 g. (1 mole) of thiourea, 130 g. (1 mole) of commercial ethyl acetoacetate, 120 g. of commercial sodium methoxide, and 900 ml. of methanol. The reaction mixture is heated gently on the steam bath and is permitted to evaporate to dryness in a hood over a period of about 8 hours. The residue is dissolved in 1 l. of hot water; the solution is treated with a few grams of activated carbon and is filtered. The hot filtrate is carefully treated (Note 1) with 120 ml. of glacial acetic acid. The thiouracil precipitates rapidly and is collected on a 4-in. Büchner funnel. The still wet solid filter cake is suspended in a boiling solution of 1 l. of water and 20 ml. of glacial acetic acid. The slurry is stirred and mixed thoroughly to break up lumps and is then refrigerated.

The product is collected on a 4-in. Büchner funnel and is washed with about 200 ml. of cold water in four portions. The solid is permitted to drain (with suction) for several hours and is then transferred to an oven at 70° for more complete drying. The yield of oven-dried 2-thio-6-methyluracil is 98–119 g. (69–84%). This material is sufficiently pure for the desulfurization reaction (Note 2).

B. 4-Methyl-6-hydroxypyrimidine. To a hot solution of 10 g. (0.07 mole) of 2-thio-6-methyluracil in 200 ml. of distilled water and 20 ml. of concentrated aqueous ammonia in a 500-ml. round-bottomed flask is added 45 g. (wet paste) of Raney nickel catalyst (Note 3). About 30 ml. of distilled water is used to wash all the nickel catalyst into the reaction flask. The mixture is heated under reflux in a hood for about 1.5 hours. The catalyst is permitted to settle, and the clear solution is decanted and filtered by gravity. The catalyst is washed with two 75-ml. portions of hot water and is discarded (Note 4). The combined filtrate and washings (Note 5) are evaporated to dryness on a steam bath. The residue is placed in an oven at 70° to complete the drying process (Note 6). The yield of crude pyrimidine, m.p. 136–142°, is 7.0–7.2 g. (90–93%).

The crude product is best purified by sublimation under reduced pressure (100–110°/1 mm.) (recovery 90–95%). Purification can also be effected by recrystallization from acetone (recovery 80–90%), ethyl acetate (recovery 70–80%), or ethanol (recovery 60–70%). The purified 4-methyl-6-hydroxypyrimidine melts at 148–149°.