Urea, Reaction with Nitrous

An alternative procedure (Method B) for the synthesis of imidazo[5,l-reacted with isocyanates to yield the ureas 17 which cyclize by reaction with nitrous acid.36,47,48... 

Methyl urea and ethyl carboxamido acetate imdeigoes transesterifieation to yield a diamide which on treatment with alkali gives rise to a pyrimidone. The resulting product on reaction with nitrous acid followed by reduetion gives a diamine which on being treated with formic acid produces a purine and when subjeeted to monomethylation yields finally the theobromine. 

Under the same conditions the even more reactive compounds 1,6-dimethylnaphthalene, phenol, and wt-cresol were nitrated very rapidly by an autocatalytic process [nitrous acid being generated in the way already discussed ( 4.3.3)]. However, by adding urea to the solutions the autocatalytic reaction could be suppressed, and 1,6-dimethyl-naphthalene and phenol were found to be nitrated about 700 times faster than benzene. Again, the barrier of the encounter rate of reaction with nitronium ions was broken, and the occurrence of nitration by the special mechanism, via nitrosation, demonstrated. 

Reaction of lH-imidazole-4-carboxilic acid amide with nitrous acid leads to the diazonium salt (5-diazenyl-l-H-imidazole-4-carboxilic acid amide). Condensation of the diazonium salt with methylisocyanate leads to initial formation of unstable urea which cyclizes under the reaction condition to give 3,4-dihydro-3-methyl-4-oxoimidazo(5,l-d)-l,2,3,5-tetrazine-8-carboxamide (temozolomide). 

The conversion of secondary azetidines into amides, carbamates, sulfonamides and ureas is accomplished without difficulty by the usual procedures a number of these derivatives are listed in Tables 1, 2 and 3. An extensive survey of these reactions has been csxried out -with 3-phenylazetidine. T -Nitroso derivatives ore obtuned -with nitrous acid, and. y-mirofiO -S-phenylaeetidine has been reduced with lithium... 

Dimethyl urea is prepared by the interaetion of urea and methylamine, whieh upon treatment with eyanoaeetie aeid yields an open-chain nitrite with the elimination of a molecule of water. This resulting compoimd undergoes cyclization in the presence of alkali. The cyclized compound on treatment with nitrous acid, followed by reduction, reaction with formic acid and subsequently with alkali gives rise to the formation of theophylline, which upon methylation finally yields caffeine. 

Structure.—The constitution of creatine is uncertain. Its conventional synthesis and many of its reactions indicate that it is a guanidine derivative of sarcosine. The solute, however, is slightly acid, and has none of the basic properties associated with the guanidines or the amino group. Unhke the amino acids, it does not react readily with nitrous acid or with formaldehyde, and on boiling with weak alkahes it is hydrolysed to sarcosine and urea. 

Amino[2- C]uracil (301. accessible from ethyl cyanoacetate and [2- C]urea as previously mentioned, is one of the key intermediates in the Traube-type synthesis of labeled uric acid and xanthine, whose methyl homologues are important biologically active natural products. Nitrosation at C5 with nitrous acid and reduction of the nitroso group with sodium dithionate installed the 5-amino group. Heating of the resulting 5,6-[2- C]diaminouracil (441 in formamide or formic acid resulted in the initial formation of the iV-formamide at C5, which cyclized with elimination of water to afford [2- C]xanthine (451 ". (V-methylation with dimethyl sulfate in basic medium under adequate reaction conditions enabled the separate preparation of [2- C]theobromine ... 

Alkaline solutions of mononitroparaffins undergo many different reactions when stored for long periods, acidified, or heated. Acidification of solutions of mononitro salts is best effected slowly at 0°C or lower with weak acids or buffered acidic mixtures, such as acetic acid—urea, carbon dioxide, or hydroxyl ammonium chloride. If mineral acids are used under mild conditions, eg, dilute HCl at 0°C, decomposition yields a carbonyl compound and nitrous oxide (Nef reaction). 

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