Pivalic acid → 2-t-Butyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine

Participants

Reaction Conditions

Reaction Steps

The feed solution was comprised of 41.4 percent pivalic acid, 43.9 percent 1,3-diamino-2-propanol, and 14.6 percent water, corresponding to a 1/1.2/2 molar ratio, and was kept warm on a hot plate stirrer and pumped through a heated line to the catalyst bed. Pivalic acid (167.4 g, 1.64 mol), 1,3-diamino-2-propanol (177.5 g, 1.97 mol), and water (59.0 g, 3.28 mol) were pumped as a single feed to the alumina bed held at 275° C., at a rate of 1.5 g/min. A preheater tube held at 250° C. served to vaporize the feed components. A nitrogen flow rate of 210 mL/min was applied to the reactor during the run. The reactor effluent was condensed with a hot water condenser to prevent crystallization. The product consisted of an orange oil containing crystalline solid and was stripped on a rotary evaporator to remove water. A roughly equal volume of acetonitrile was added, the slurry cooled to 0° C., and crystalline product was collected on a filter and dried in a vacuum oven at 60° C. to give 139.2 g of 2-t-butyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine as a first crop. The mother liquor was reduced in volume to give an orange oil and placed in an oven at 80° C. overnight. After addition of acetonitrile to the resulting solid and filtration as above, an additional 60.1 g solid was obtained, which was 84 percent pure, most of the remainder being uncyclized materials. The total of 189.7 g of 2-t-butyl-5-hydroxy-1,4,5,6-tetrahydropyrimidine represented a 74 percent isolated yield based on pivalic acid, and a 62 percent yield based on 1,3-diamino-2-propanol. A pure sample was prepared by recrystallization from warm CH3CN: mp 212°-214° C. (corrected, decomp); 1H NMR (D2O/CD3CN) δ 3.9 (m, 1H), 3.1 (apparent dt, 2H), 2.9 (apparent dd, 2H), 1.0 ppm (s, 3H); 13C NMR {1H} (D2O/CD3CN) δ 168.7 (1 C), 60.0 (1 C), 47.0 (2 C), 37.0 (1 C), 27.7 ppm (3 C); Anal. Calcd for C8H16N2O: C, 61.50; H, 10.32; N, 17.93. Found: C, 61.57; H, 10.50; N, 18.01.

Provenance & Evidence