1- 5-methyluracil

The dry, finely powdered, crude jS-uraminocrotonic ester is stirred into a solution of 80 g. (2 moles) of sodium hydroxide in 1200 cc. 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 

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 course of 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 and urea was described first by Behrend.i The substance has been obtained also by the action of lead hydroxide on methylthiouracil in an alkaline medium, and by boiling benzalmethylhydroxypyri-midinhydrazine with hydrochloric acid.  

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Hydroxymethyl-6-methyluracil (1043) was prepared many years ago from 6-methyl-uracil and formaldehyde, or in other ways. Since 1956 it has received much attention in the USSR under the (transliterated) name pentoxyl or pentoxil. It is used in several anaemic and disease conditions. For example, a mixture of folic acid and pentoxyl quickly reduces the anaemia resulting from lead poisoning pentoxyl stimulates the supply of serum protein after massive blood loss it stimulates wound healing it stimulates the immune response in typhus infection and it potentiates the action of sulfonamides in pneumococcus infections (70MI21300). 

In 1962, bromacil (5-bromo-3-s-butyl-6-methyluracil 1047 R = Bu ), its homologue (isocil 1047 R = Pr ) and related iV-alkyluracils were shown to have valuable selective phytotoxic properties and vitually no mammalian toxicity. Thus, bromacil achieves a complete kill of most unwanted broad-leaf annuals or perennials along with some grasses... 

Amidines react with P-keto esters to provide hydroxypyrimidines. The synthesis of the 2,6-dimethyl-4-hydroxylpyrimidine (9) has been improved dramatically by combining Pinner s procedure with that of Donleavy et al. for the synthesis of 6-methyluracil. 

Methyl 2-thienyl ketone, 18,1 i-Methylthiol-3-phthalamidopropane-3,3-dicarboxylic acid, 14, 59 6-Methyluracil, 17, 63 Monochlorumethyl ether, 14, 92 Morland salt, 15, 75 Myristic acid, 18, 84 Myristyl alcohol, 10, 64 Myristyl bromide, 16, 26 16, 37... 

Chemical name 3-ferf-Butyl-5-chloro-6-methyluracil... 

Bromacil (5-bromo-3-sec-butyl-6-methyluracil), Lenacil (3-cyclohexyl-5,6-trimethyleneuracil) and Terbacil (5-chloro-3-tertbutyl-6-methyluracil) herbicides... 

Bromo -3 - (3 -hydroxy-1 -methylpropyl) -6-methyluracil, see Bromacil 2-Bromo-3-hydroxypropene, see l,2-Dibromo-3-chloropropane... 

CASRN 314-40-9 molecular formula C9Hi3BrN202 FW 261.12 Soil Metabolites tentatively identified in soil were 5-bromo-3-(3-hydroxy-l-methylpropyl)-6-methyluracil, 5-bromo-3-5ec-butyl-6-hydroxymethyluracil, 5-bromo-3-(2-hydroxy-l-methylprop-yl)-6-methyluracil, and carbon dioxide. The presence of uracil products suggests that bromacil was degraded via hydroxylation of the side chain alkyl groups. In the laboratory, 25.3% of C-bromacil degraded in soil to carbon dioxide after 9 wk but mineralization in the field was not observed. The half-life of bromacil in a silt loam was 5-6 months (Gardiner et al, 1969). 

Photolytic. When a dilute aqueous solution (1-10 mg/L) of bromacil was exposed to sunlight for 4 months, the TV-dealkylated photoproduct, 5-bromo-6-methyluracil, formed in small quantities. This compound is less stable than bromacil and upon further irradiation, the de-brominated product, 6-methyluracil was formed (Moilanen and Crosby, 1974). Acher and Dunkelblum (1979) studied the dye-sensitized photolysis of aerated aqueous solutions of bromacil using sunlight as the irradiation source. After 1 h, a mixture of diastereoisomers of 3-5ec-butyl-5-acetyl-5-hydroxyhydantoin formed in an 83% yield. In a subsequent study, another minor intermediate was identified as a 5,5 -photoproduct of 3-5ec-butyl-6-methyluracil. In this study, the rate of photooxidation increased with pH. The most effective sensitizers were riboflavin (10 ppm) and methylene blue (2-5 ppm) (Acher and Saltzman, 1980). Direct photodegradation of bromacil is not significant (Acher and Dunkelblum, 1979 Ishihara, 1963). 

Orotic acid or 6-methyluracil vide infra), when administered to rabbits with myocardial infarction induced by ligation of the anterior descending branch of the left coronary artery, can decrease the incidence of necrosis and increase the rate of regeneration for healthy cellular and fibrous connective tissue in the infarct region [182]. Rats with induced aortal stenosis which are treated with... 

Aqueous suspensions of 6-methyluracil, when administered orally to rats, accelerate and intensify the assimilation of alimentary carbohydrates and increase hepatic glycogen synthesis [267]. 

Methyluracil was found to decrease the toxic effects of large doses of potassium benzylpenicillin or Bicillin 5 and to eliminate the undesirable effect of dichlorotetracycline on tissue cells [268, 269]. The combination of one of these antibiotics with 6-methyluracil decreases the number of degenerating cells... 

When administered into the newly developed chicken embryo, 6-methyluracil was found to possess strong teratogenic activity. The compound produces abnormalities in 85 per cent of the embryos at 4 mg/kg [270]. In pregnant rats this pyrimidine causes damage to 10-day-old embiyos. Microanatomical examination reveals urogenital system abnormalities (e.g. hydronephrosis, uretal oedema) [271]. 

Gastric ulcers induced in rats by repeated administration of caffeine can be reduced by the administration of 6-methyluracil. Treatment is more effective when this compound is combined with either 2-methyl-4,6-dihydroxypyrimidine or cytosine [273]. In a study of the influence of 6-methyluracil and uracil on experimental blastomogenesis in mice, it was found that 6-methyluracil reduces the frequency of urethan-induced lung adenoma whereas uracil increases the instances [274]. 6-Methyluracil, like orotic acid, can restore experimentally induced infarction in rabbits [179-182]. 

Nitro-6-methyluracil, like 6-methyluracil, was reported to produce abnormalities in 75 per cent of the embryos by intermpting basic development of the organs [270]. 

The uracils with herbicidal activity do not necessarily contain 5-halo substituents. 3-Cyclohexyl-5-methyluracil [354] (XLIV), l,3-di-isopropyl-6-methyl-uracil [352] (XLV) and 3-s-butyl-5-thiocyanato-6-methyluracil [353] (XLVI), for example, are cited as having this type of activity. 3-Butyl-6-methyluracil (XLlllc) possesses interesting selective activities. For instance, this pyrimidine kills many annual weed species without damage to peas and peanuts, even when applied at twice the concentration needed to kill the weeds [346]. On the other hand, the related 5-bromo derivatives, such as (XLlIlb), are useful as industrial herbicides where it is desirable to kill all plants [346]. 

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