Ureas nitrosation

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. 

C-5, nitrosation yields 384 (Scheme 219). If alkylisocyanates replace alkylisothiocyanates, the corresponding thioureas (382b) (X = S) are obtained (482). Tertiary ureas 386 are prepared by reaction... 

Rate measurements were also carried out81 in the presence of added urea in an attempt to remove the free nitrite species formed and so prevent N-nitrosation (the reverse of de-nitrosation). The observed rate coefficient was now found to be the sum of the rate coefficients for rearrangement (kr) and de-nitrosation (ka)... 

Hard evidence for the first category seems to be nonexistent. An educated guess on the potential hazards would combine residue technology [how much of a secondary amine (or amide, urea, carbamate, etc.) might a person consume or otherwise be exposed to ], nitrosation chemistry (what would be the yield of in vivo nitrosation of the pesticide thus consumed ), and toxicology (what would be the toxicological effect and potency of the nitroso compound thus formed ). Frequently, these questions, which simplify to, "What dose—eg., in mg/kg—of a pesticide-derived nitroso compound might a person be exposed to and what would be the result if he were " are not carefully considered. 

BCNU is synthesized by treating phosgene with ethyleneimine without the addition of a base to take up the HCl liberated. Reaction of the intermediate urea (46) in situ with hydrogen chloride serves to open the aziridine rings to afford sym-bis-2-chlorethylurea (47). This is nitrosated with sodium nitrite in formic acid to give BCNU (48). 

N-Aminoimidazolinones have found extensive use as synthons for such nitrofurans. Reaction of an appropriate 1,2-diamine (27, 31) with urea gives the desired heterocycle (28, 32). Nitrosation with... 

Nitrosation of primary amides results in deamination to produce carboxylic acid and nitrogen as products. Secondary amides, when nitrosated, give the corresponding nitrosamides in a reversible process [51]. In order to obtain good yields of the nitrosamides, it is best to add a base to remove the acid formed (Scheme 3.2). This reaction also occurs with ureas and carbamates. 

Thust, R., Mendel, J., Schwarz, H. and Warzoki, R. (1980). Nitrosated urea pesticide metabolites and other nitrosamides. Activity in clastogenicity and SCE assays, and aberration kinetics in Chinese hamster V79-E cells. Mutation Res. 79 239-248. 

The nitrosation of A-alkylureas in dioxane-acetic acid mixtures is governed by the expression v = fc[HN02][urea], at fixed pH, and dependent on rate-determining proton transfer from the protonated iV-alkyl-iV-nitrosourea to acetate anion the order of reactivity, which reflects relative impediment by the alkyl groups, is as for nitrosation in aqueous media (methyl- ethyl- propyl- butyl- > allyl-urea). 

In view of the various possible pathways for nitrosation of amines as well as of amine derivatives (amides, ureas, carbamates, etc. ), it is not unexpected then for N-nitroso compounds to be found in many different areas of the human environment (11). It is possible that N-nitroso compounds may represent a carcinogenic exposure which most people experience on a daily basis. The list of items that have now been demonstrated to have measurable levels of various N-nitroso compounds present within them has grown considerably over the past decade (, 11, 12). A portion of this list would include air, water, soil, cheese, meats, fish, eggs. 

Substituted ureas have been nitrosated in aqueous systems primarily to obtain intermediates for the preparation of diazoalkanes [47, 48]. The base-induced decomposition of A-nitroso-A-(2,2-diphenylcyclopropyl) urea has been studied [49], and a series of l,3-bis(2-chloroethyl)-l-nitrosoureas and l,5-bis(2-chloroethyl)-l-nitrosobiurets have been studied as potential anticancer agents [50],... 

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