A. N-n-Heptylurea. To a mixture of 24.1 g. (0.21 mole) of n-heptylamine (Note 1), 35 g. of cracked ice, and 150 ml. of ice-cold water is added 38 ml. of 5N hydrochloric acid (Note 2) with stirring. The mixture is heated on the steam bath at 70–80°, and 14.3 g. (0.22 mole) of sodium cyanate is added portion-wise. After 2–4 hours of continued heating, two layers separate. The product crystallizes on standing overnight at room temperature. It is collected on a Büchner funnel, washed with 100 ml. of cold water, and drained as dry as practical by suction. This solid is dissolved in 125 ml. of boiling ethyl acetate, and the resulting solution is cooled to room temperature. The white crystalline N-n-heptylurea is filtered and dried on a porcelain plate at room temperature. A yield of 28.5–29.5 g. (86–88%) of product melting at 110–111° is obtained (Note 3).

B. 3-n-Heptylureidomethylenemalononitrile. In a 250-ml. round-bottomed flask fitted with a heating mantle and a reflux condenser are placed 28.5 g. (0.18 mole) of N-n-heptylurea, 11.9 g. (0.18 mole) of malononitrile (Note 4), and 26.7 g. (0.18 mole) of triethyl orthoformate (Note 4). The mixture is heated under reflux for 2 hours and then cooled in ice. The solid product is collected by suction filtration on a Büchner funnel. The filtrate is concentrated on the steam bath to incipient crystallization, cooled, and filtered. The two lots of tan solid, 41–42 g., thus obtained are dissolved in 75 ml. of 75% ethyl alcohol in a 250-ml. beaker, 2 g. of decolorizing carbon is added, and the mixture is boiled for 2–3 minutes with constant stirring (necessary to avoid vigorous bumping). The hot solution is filtered by gravity into a 250-ml. Erlenmeyer flask through fluted filter paper. The flask is stoppered and cooled in the refrigerator for 4 hours. The solid product is collected by suction filtration on a Büchner funnel and washed four times with 10-ml. portions of distilled water. The white crystalline 3-n-heptylureidomethylenemalononitrile is dried at 50° in a vacuum oven. It melts at 130–132° and amounts to 33.8–34.8 g. (80–83%) (Note 5).

C. 3-n-Heptyl-5-cyanocytosine. In a 250-ml. Erlenmeyer flask are placed 33.8 g. (0.145 mole) of 3-n-heptylureidomethylenemalononitrile and 70 ml. of methanol; then 8.5 g. (0.16 mole) of sodium methoxide (Note 6) is added carefully in small portions (Note 7). The resulting solution is allowed to stand at room temperature for 3 days in the stoppered flask. The contents of the flask are dissolved in 300 ml. of cold water in an 800-ml. beaker, and the solution is stirred as 11 ml. of glacial acetic acid is added. The precipitated solid is collected by suction filtration on a Büchner funnel and washed with three 40-ml. portions of distilled water. The undried product is dissolved in 600 ml. of hot ethyl alcohol; then the solution is filtered into a 1-l. flask by gravity through a fluted filter paper, concentrated on the steam bath to 200 ml., and cooled in the refrigerator for 4 hours. The 3-n-heptyl-5-cyanocytosine crystallizes in white needles, melts at 192–197° (Note 8), and amounts to 29.7–31.1 g. (88–92%) (Note 9).

Recrystallization of 20 g. of this product from 230 ml. of hot ethyl alcohol affords 17.8 g. of fine colorless needles, m.p. 199.5–202.5°.