Org. Synth. 1937, 17, 63
Submitted by John J. Donleavy and Mearl A. Kise.
Checked by Reynold C. Fuson and William E. Ross.
Eighty grams (1.33 moles) of finely powdered urea is stirred into a mixture of 160 g. (155 cc., 1.23 moles) of ethyl acetoacetate (Note 1), 25 cc. of absolute alcohol (Note 2), and ten drops of concentrated hydrochloric acid in a 5-in. crystallizing dish. The reagents are mixed well, and the dish is covered loosely with a watch glass and placed in a vacuum desiccator over concentrated sulfuric acid. The desiccator is evacuated continuously with a water pump until the mixture has gone to dryness (Note 3), which usually requires from five to seven days (Note 4). The crude β-uraminocrotonic ester when thoroughly dry weighs 200–205 g.
The dry, finely powdered, crude β-uraminocrotonic ester is stirred into a solution of 80 g. (2 moles) of sodium hydroxide in 1.2 l. of water at 95°. The clear solution is then cooled to 65° and carefully acidified, while stirring, by the slow addition of concentrated hydrochloric acid. The 6-methyluracil precipitates almost immediately, and after the mixture is cooled the product is collected on a filter, washed with cold water, alcohol, and ether, and air-dried. The substance is obtained as a colorless powder of a high degree of purity, and the yield is 110–120 g. (71–77 per cent of the theoretical amount). For further purification the pyrimidine may be crystallized from glacial acetic acid. 6-Methyluracil decomposes above 300°.
Larger amounts of alcohol increase the period of drying without improving the yield. When no alcohol is used, the condensation proceeds slowly and the yields are low.
If the condensation product is used before it is dry, a large amount of carbon dioxide
is evolved later in the acidification, indicating incomplete utilization of the ethyl acetoacetate
It is usually advisable to change the sulfuric acid
at least daily. Any lumps should be disintegrated occasionally to aid in the drying process.
The synthesis of 6-methyluracil
from ethyl acetoacetate
was described first by Behrend.1
The substance has been obtained also by the action of lead hydroxide
in an alkaline medium;2
by boiling benzal-2-(4-hydroxy-6-methyl) pyrimidylhydrazine
with hydrochloric acid
and from urea
Chemical Abstracts Nomenclature (Collective Index Number);
sulfuric acid (7664-93-9)
hydrochloric acid (7647-01-0)
acetic acid (64-19-7)
sodium hydroxide (1310-73-2)
carbon dioxide (124-38-9)
Ethyl acetoacetate (141-97-9)
Uracil, 6-methyl- (626-48-2)
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