Nitrous acid reaction with urea

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. 

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. 

Commercial 70 % nitric acid can be used for the 6>-nitration of low molecular weight alcohols like ethanol and 2-propanol. The nitrate ester products are isolated from the cautious distillation of a mixture of the alcohol and excess 70 % nitric acid. The presence of urea in these reactions is very important for the destruction of nitrous acid and its omission can lead to very violent fume-off. However, this method is not recommended on safety grounds. Using temperatures above ambient for the O-nitration of alcohols, with either nitric acid or mixed acid, is dangerous and greatly increases the risk of explosion. 

A mixture of concentrated sulfuric and nitric acids has been used for the A-nitration of amides and ureas. A, A -Dinitro-A,A -bis(2-hydroxyethyl)oxamide dinitrate (NENO) (11) is prepared from the action of mixed acid on A, A -bis(2-hydroxyethyl)oxamide (61), itself prepared from the condensation of diethyloxalate with two equivalents of ethanolamine. Niuo-sylsulfuric acid is an inhibitor of A-nitration and so nitrous acid should be rigorously excluded. The reaction of (61) with absolute nitric acid results in 6>-nitration of the hydroxy groups but no A-nitration, and consequently, (62) is isolated as the sole product. 

One type of chemical approach to the analysis of liquid and solid hydrocarbons that will probably see considerable development is that involving reaction or complex formation to yield precipitates that can be separated from the unreacted mass and subsequently be treated to regenerate the hydrocarbons or class of hydrocarbons so precipitated. This field is certainly not extensively developed. In fact very few examples come to mind but among these are Gair s (21) determination of naphthalene by precipitation with picric acid determination of benzene by Pritzker and Jungkunz (52) by an aqueous solution of specially prepared nickel ammonium cyanide Bond s (8) nitrous acid method for styrene and more recently the determination of normal alkanes in hydrocarbons of more than 15 carbon atoms by adduct formation with urea as described by Zimmerschied et al. (71). 

In 7-5 % aqueous sulpholan the very reactive compound, anthan-threne, could be nitrated according to a first-order law only with low concentrations of nitric acid, and the reaction was very strongly catalysed by nitrous acid. Under zeroth-order conditions (i.e. in the absence of water and with [HN03] = 5 mol l-1) and with a very small concentration of nitrous acid ([HN02] < 3 x io 5 mol l-1 [urea] = 0-05 mol l-1), where the use of mesitylene gave k0 = 2 ix io-8 mol l-1 s 1 (at 25 °C), the nitration of anthanthrene was too fast to be measured. Clearly, the nitronium ion mechanism could not be operative. With low concentrations of nitric acid ([HN03] < 1 mol l-1) zeroth-order nitration of anthanthrene of the same rate as that for mesitylene could with difficulty be observed often autocatalysis intervened.31... 

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). 

Nitrourea is decomposed quantitatively into cyanic acid and nitrous oxide when heated in aqueous solution. If primary or secondary amines are present, the products are alkylureas or N,N-diaIkylureas, respectively.Alcohol is used as a solvent for amines which are only slightly soluble In water. The yields in general are excellent (70-98%), and the reaction is preferred to the exchange with urea described above. Alkanolamines give hydroxyalkylureas in 85-95% yields." Nitrourea is conveniently prepared in 90% yield from urea nitrate."... 

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... 

Hypobromite Reaction.—When treated with hypobromites or nitrous acid urea is oxidized and carbon dioxide water and nitrogen gas are obtained. 

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