3475-63-6

Usage

Safety Profile

Poison by ingestion and intravenous routes. Experimental teratogenic effects. Questionable carcinogen with experimental tumorigenic data. Mutation data reported. Many N-nitroso compounds are carcinogens. When heated to decomposition it emits toxic fumes of NOx. See also N-NITROSO COMPOUNDS.

InChI:InChI=1/C4H9N3O2/c1-6(2)4(8)7(3)5-9/h1-3H3

Upstream product

• 632-14-4 1,1,3-trimethylurea 

Downstream Products

• 5632-47-3 N-nitrosopiperazine 
• 67-56-1 methanol 
• 632-14-4 1,1,3-trimethylurea 
• 124-40-3 dimethyl amine 

Relevant academic research and scientific papers

STRUCTURE DE LA N-METHYL-N-NITROSO-N'-NITROGUANIDINE ET DE LA TRIMETHYL NITROSO UREE: ETUDE PAR RMN 15N

A 15N NMR study of N-methyl-N-nitroso-N'-nitroguanidine (MNNG) in solution has allowed its structure to be determined.This is then compared with those of two other nitroguanidines.Electronic delocalisation in MNNG is attempted in connection with trimethylnitroso urea.

Unexpected genetic toxicity to rodents of the N′,N′-dimethyl analogues of MNU and ENU

Lijinsky and his colleagues have reported that the N′,N′-dimethyl analogues of ENU and MNU [N′,N′-dimethyl-N-ethyl-N-nitrosourea (DMENU) and trimethylnitrosourea (TMNU), respectively] are carcinogenic to rats despite their extreme hydrolytic stability which would reduce or preclude generation of alkylating species analogous to those formed upon hydrolysis of ENU and MNU. Lijinsky and his colleagues were unable to rationalize those activities of DMENU and TMNU despite extensive experimentation. We therefore decided to study this problem further. Whichever mode is accepted for the generation of electrophilic/mutagenic/carcinogenic reactive species from ENU and MNU, blocking of the free-NH2 group with methyl groups [-NMe2) should ablate or abolish activity. Consistent with this, DMENU and TMNU gave negative results in the NBP alkylation test while the parent compounds gave an instantaneous deep blue coloration. Studies of the rate of hydrolysis of these four compounds revealed ENU and MNU to have half-lives of 8 min, while the alkylated analogues (DMENU and TMNU) had half-lives of 25 and 41 days, respectively. Hydrolysis of ENU and MNU, to yield the alkylating species, proceeds either via proton abstraction from the - NH2 group or by attack by water on the carbon of the carbonyl group. Methylation will inhibit both of these pathways, the first absolutely (no -NH2 protons) and the second partially, via steric inhibition. The slow hydrolysis observed for DMENU and TMNU suggests that the latter route of hydrolysis is applicable. Studies with strain TA1535 of Salmonella typhimurium (without S9 mix) confirmed the potent mutagenic activity for ENU and MNU (～300-fold increase in revertants at 2,000 p.g/plate and ～180-fold increase in revertants at 150 μg/plate respectively). In contrast, the methylated analogues showed only weak mutagenic activity (～3-fold) at ~100-fold higher dose-levels. Addition of S9 mix did not affect the mutagenicity of DMENU or TMNU. To this point, hypothesis and data coincide. ENU and MNU are potent micronucleus-inducing agents to the mouse bone marrow, and given the above data, it was expected that DMENU and TMNU would show weak or no activity in that assay. In fact, the methylated analogues were as effective as ENU and MNU as clastogens to the mouse bone marrow. Four possible reasons for this conflict of theory and data are explored. The speculative explanation we favour for these effects is that the net alkylation of bone marrow DNA is the same for all four chemicals. With ENU and MNU, most of the alkylating activity is dissipated by rapid hydrolysis. Thus, only a small fraction of the administered dose survives to alkylate the bone marrow. Due to the enhanced stability of the methyl analogues most of the delivered dose will reach the bone marrow. However, because of their lower intrinsic reactivity, only a small fraction of the target dose will alkylate the bone marrow DNA during the time window of the experiment. If these opposing influences happen to balance out, the essentially identical bone marrow genetic toxicity for the four chemicals could be explained.

Conformational Preferences in Alkylnitrosoureas

The spectroscopic properties of several N-alkyl-N-nitrosoureas, N,N'-dialkyl-N-nitrosoureas, and N,N',N'-trialkyl-N-nitrosoureas have been studied in carbon disulfide and chloroform solutions.The NH stretching frequencies in the IR spectra have been observed in both concentrated and dilute solution and in the presence of added dioxane.The results indicate that there is a strong intramolecular hydrogen bond in the mono- and dialkylnitrosoureas.The chemical shifts and line widths of the NMR spectra have also been studied in these solvents.The large chemical shift differences, about 1.3 ppm, for the NH protons in the monoalkylnitrosoureas and other spectroscopic features in the monoalkyl- and dialkylnitrosoureas also indicate that an intramolecular hydrogen bond contributes to a strong conformational preference.The temperature dependence of the NMR spectra of several N,N',N'-trialkyl-N-nitrosoureas establishes that the energy barrier for rotation about the carbon dialkylamide bond is about 13 kcal mol-1.Dipolar resonance interactions are primarily responsible for this barrier.This interaction is augmented by a strong, 8-10 kcal mol-1, hydrogen bond in the mono- and dialkylnitrosoureas.