Deamination of Some N-Amino Nitrogen Heterocycles Using Preyssler’s Anion

Summary. Some N-aminotriazines and -triazoles were treated with Preyssler’s anion as catalyst in acetic acid to afford the corresponding deaminated triazines and triazoles. The reaction is suggested to proceed via formation of N-nitrosamines with subsequent N–NO bond cleavage.     

Ionic liquid 1-(4-nitritobutyl)-3-methylimidazolium chloride as a new reagent for the efficient N-nitrosation of secondary amines under mild conditions

Abstract  

1-(4-Nitritobutyl)-3-methylimidazolium chloride has been developed as a new reagent for efficient nitrosation of secondary amines at 0 °C to room temperature. A variety of N-nitrosamines were prepared in excellent yields by use of this task-specific ionic liquid under mild and heterogeneous conditions.     

Ab initio calculations relevant to the mechanism of chemical carcinogenesis by N-nitrosamines. VIII. Effects of hydration on various reactions involved in the formation and metabolism of N-nitrosamines

A number of important reactions involved in the formation and metabolism of N-nitrosamines have been studied using a modified reaction field method which treats the solute quantum mechanically and the solvent as a polarized dielectric.     

Synthesis of Partially Deuterated <Emphasis Type="Italic">N</Emphasis>-Nitrosamines – New Standards in Tobacco-smoke Analysis

Summary. N-Nitrosamines of tobacco alkaloids contribute to the cause of tobacco related cancers and, therefore, they are important analytes. Herein the preparation of four partially deuterated N-nitrosamines from simple, commercially available, deuterated educts is described, which can serve as useful standards in tobacco-smoke analysis.     

Evaluation of the influence of proline, hydroxyproline or pyrrolidine in the presence of sodium nitrite on N-nitrosamine formation when heating cured meat

N-nitrosamines are meant to be probable or possible carcinogenic components, possibly formed out of a reaction between nitrite and N-containing substances such as amino acids and secondary amines. Nitrite is often used for processing meat products because of its colouring and antimicrobial properties.During this experimental setup, the influence of proline, hydroxyproline or pyrrolidine on N-nitrosamine formation in meat samples was evaluated. The N-nitrosamines concentrations were measured with gas chromatography-thermal energy analyzer. Only the concentrations of N-nitrosodimethylamine and N-nitrosopyrrolidine were found above the limit of detection in a number of tested experimental conditions. The concentration of these two N-nitrosamines was modelled as a function of temperature and nitrite concentration for different situations (presence or absence of added natural N-containing meat components). It could be concluded that proline and pyrrolidine promoted the formation of N-nitrosopyrrolidine. It could also be confirmed that the higher the temperature of the meat processing procedure and the higher the sodium nitrite amounts added, the higher were the yields of the respective N-nitrosamines.     

Hydroacridines XXV [1]. First Synthesis of (4aα,8aα,9aβ,10aβ)-Tetradecahydroacridine and New Syntheses of (4aα,8aα,9aα,10aβ)- and (4aα,8aβ,9aα,10aβ)-Tetradecahydroacridine

Summary. On heating in dry DMSO, in the presence of potassium t-butoxide, the N-nitrosamine of (4aα,8aβ,9aβ,10aα)-tetradecahydroacridine is completely converted into the N-nitrosamine of (4aα,8aα,9aα,10aβ)-tetradecahydroacridine. Under similar conditions, the N-nitrosamine of (4aα,8aα,9aβ,10aα)-tetradecahydroacridine yields a ternary equilibrium mixture containing itself (19%), and the N-nitrosamines of (4aα,8aβ,9aα,10aβ)-tetradecahydroacridine (46%) and the so far unknown (4aα,8aα,9aβ,10aβ)-tetradecahydroacridine (35%). The resulting N-nitrosamines can be smoothly denitrosated to the corresponding secondary amines.     

Highly sensitive method for determination of N-nitrosamines using high-performance liquid chromatography with online UV irradiation and luminol chemiluminescence detection

A new method for the measurement of N-nitrosamines in part-per-trillion concentrations from water samples without preconcentration steps has been developed. This method is based on online UV irradiation after high-performance liquid chromatographic separation and subsequent luminol chemiluminescence detection without addition of an oxidant. It was confirmed that N-nitrosamines in basic aqueous solution were transformed to peroxynitrite by UV irradiation. The detection limits for this method were 1.5 ng/L, 2.9 ng/L, 3.0 ng/L, and 2.7 ng/L for N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosomethylethylamine, and N-nitrosopyrrolidine, respectively, at a signal-to-noise ratio of 3. The calibration graphs were linear in the range of 5–1000 ng/L for these N-nitrosamines. This method was used for the determination of N-nitrosamines in tap water, river water, and industrial plant effluent samples. The recoveries of N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosomethylethylamine, and N-nitrosopyrrolidine present in tap water sample at a concentration of 10 ng/L (mean ± standard deviation, n = 4) were (94.8 ± 2.7)%, (102.0 ± 6.9)%, (99.3 ± 3.9)%, and (102.8 ± 2.5)%, respectively. These results indicate that our proposed method can be applied satisfactorily to the determination of N-nitrosamines in water samples.     

Oxone-sodium nitrite mediated N-nitrosamines formation under mild conditions from secondary amines

Abstract

Herein, we report an efficient synthesis of N-nitrosamines from cyclic, aliphatic, benzylic, and aromatic secondary amines via a novel straightforward, efficient, and mild chemical process using sodium nitrite and Oxone in methanol as a solvent at 0–5?°C. The demonstrated methodology accounts well for the parameters like cost-effective, short reaction time, clean and safe handling along with good to excellent yields.     

Facile Denitrosation of Cyclic N-Nitrosamines with Hydrazoic Acid

Abstract

A simple and facile method for the denitrosation of cyclic N-nitrosamines using HN₃ (concentrated H₂SO₄ + NaN₃) is reported. In this method, limited usage of this reagent does not affect the carbonyl group.     

The use of an inexpensive electronic filter for improving detection limits in the gas chromatographic-chemiluminescent determination of nitrosamines

The construction and use of an electronic noise filter is described. It is evaluated by use with a laboratory-built selective chemiluminescent detector used for the gas Chromatographie analysis of mixtures of volatile N-nitrosamines. A ten-fold reduction in the noise level was achieved with a corresponding decrease in detection limit to 4 nl l^-1.     

N-nitrosamines and differential pulse polarography

Differential pulse polarography is a versatile and sensitive technique which yields both qualitative and quantitative information about N-nitrosamines. The ability of the technique to carry out determinations in-situ permits the study of anchimeric, metabolic, and mechanistic properties in addition to phenomena such as kinetics and transnitrosation.     

Structural studies on some N-nitramines and N-nitrosamines

INDO-MO calculations are reported for some N-nitramines and N-nitrosamines. Reasonable agreement is obtained between the calculated dipole moments of the lowest energy conformations and experimental data. The calculated energy barrier to rotation about the N-N bond in dimethyl nitrosamine and dimethyl nitramine is in good agreement with experiment. Some calculated spin-spin coupling constants for dimethyl nitramine are also reported.     

Ph3P/Br2/n-Bu4NNO2 as an efficient system for the preparation of N-nitrosamines and azides

The combination PPh₃/Br₂/n-Bu₄NNO₂ was developed as a new reagent system for the efficient preparation of N-nitrosamines and azides from the corresponding amines and hydrazine derivatives, respectively, at 0 °C to room temperature, in excellent yields.     

An IARC Manual Series Aimed at Assisting Cancer Epidemiology and Prevention. “Environmental Carcinogens: Selected Methods of Analysis”

Abstract

Since 1975, the IARC has been preparing a series of volumes entitled “Environmental Carcinogens: Selected Methods of Analysis” (IARC Manual Series) of which the purposes are to assist analysts, epidemiologists and regulatory authorities in planning or performing exposure measurements that are truly comparable between different studies. The Manual series provides expert information within each volume on multimedia sampling, methods of analyses and some background of epidemiology, metabolism, use/occurrence for a group of known or suspect carcinogens. So far, eleven volumes have been published or are in preparation on the following subjects: (1) N-nitrosamines, (2) vinyl chloride, (3) PAH, (4) aromatic amines, (5) mycotoxins, (6) N-nitroso compounds, (7) volatile halogenated hydrocarbons, (8) metals, (9) passive smoking, (10) benzene and alkylated benzenes, (1) dioxins, PCDFs and PCBs.     

Automatic screening method for the preconcentration and determination of N-nitrosamines in water

A screening method was developed to discriminate among water samples contaminated or uncontaminated with N-nitrosamines in order to reduce the use of expensive instruments such as chromatographs. The system is based on the preconcentration of the analytes onto a sorbent column, elution and derivatization to form nitrite, then formation of a coloured product (Griess reaction) and photometric detection. The limit of detection achieved for 100 ml of sample volume was 0.2 μg/l and the sample frequency 3 h⁻¹. The reliability of the proposed method of the N-nitrosamines was established at five concentrations (between 0.5 and 3 times the limit of detection). For a level concentration of 0.6 μg/l (three times the limit of detection), the percentage of false negatives is 0%. The method was applied to the screening of several water samples (river, pond, well, tap and waste) with a positive response only for waste water samples.     

Study of the metabolism on tobacco-specific N-nitrosamines in the rabbit by solid-phase extraction and liquid chromatography–tandem mass spectrometry

Metabolism of four tobacco-specific N-nitrosamines (TSNAs), N′-nitrosonornicotine (NNN), N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) has been studied by solid-phase extraction (SPE) and liquid chromatography–tandem mass spectrometry (LC–MS–MS). 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was used as internal standard. SPE and LC–MS–MS was found to be a rapid, simple, sensitive, and selective method for analysis of TSNAs in rabbit serum. The relative standard deviation (R.S.D., n = 6) for analysis of 5 ng mL⁻¹ and 0.5 ng mL⁻¹ standards and of serum sample spiked with 5 ng mL⁻¹ standards of five TSNAs was 2.1–11% and recovery of 5 ng mL⁻¹ standards from serum was 100.2–112.9%. A good linear relationship was obtained between peak area ratio and concentration in the range of 0.2–100 ng mL⁻¹ for NNAL and 0.5–100 ng mL⁻¹ for other four TSNAs, with correlation coefficients (R ²) >0.99 (both linear and log–log regression). Detection limits for standards in solvent were between 0.04 and 0.10 ng mL⁻¹. Doses of TSNAs administered to rabbits via the auricular vein were 4.67 μg kg⁻¹ and 11.67 μg kg⁻¹, in accordance with the different levels in cigarettes. Metabolic curves were obtained for the four TSNAs and for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of NNK; on the basis of these curves we modeled metabolic kinetic equations for these TSNAs by nonlinear curve fitting.     

Photolysis of N-nitrosamines in neutral media

The photolysis of N-nitrosamines in solutions of acetonitrile follows a first-order reaction with respect to the concentration of nitrosamine. Quantum yields are very low (≈ 0.1) and depend on the concentration of nitrosamine, with the observation of a linear correlation between the reciprocal of quantum yield and the reciprocal of nitrosamine concentration. For all the nitrosamines studied, the final product of the photolysis appears to be unique, alkylidenimine, which in the case of nitroso methyl benzyl amine undergoes a relatively rapid hydrolysis, giving rise to benzaldehyde, following second order kinetics. A provisional model consistent with the experimental results obtained in this work is proposed. © 1993 John Wiley & Sons, Inc.     

Trace determination of amines and other nitrogen containing compounds with a modiefied thermal energy analyzer (TEATM)

Summary A modification to the TEA^TM Analyzer is described, which allows it to be used as a highly selective GC detector for nitrogen compounds as well as for N-nitrosamines and nitro compounds. The modified Analyzer is as sensitive as the AFID, but has a much higher selectivity towards nitrogen compounds than the AFID. Its response appears to be molar, with an output that is dependent only on the number of nitrogen atoms present. The performance of the modified Analyzer for the analysis of ammonia, amines,N-nitrosamines, nitriles and organonitro compounds is reported and discussed, as is its application to the detection of these compounds in bacon and beer samples.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Structure–activity relationship of nitrosating agents in the nitrosation reactions of ammonia: a theoretical study

Nitrosating agents (NAs) stimulate the formation of powerful mutagenic and carcinogenic N-nitrosamines. As a model reaction, the nitrosation of ammonia by a series of NAs, i.e., HONO, N₂O₃, N₂O₄, ONOOH, ONCl, ONBr, ONSCN, ONOCH₃, ONOC₂H₅, ONNC, ONOCl, and ONOSOCH₃, was investigated at the CBS-QB3 level of theory. A structure–activity relationship of NAs in the nitrosation reactions of ammonia was established. The results indicate that the nitrosating reactivity of NAs (ON–X) has definite relationship with the heterolytic bond dissociation energies of ON–X and H–X, Mulliken charges of N and X atoms as well as number of the atoms in the ring of the transition state. In light of the established structure–reactivity relationship of NAs, ONNC was found to be a potential powerful nitrosating species.     

Molecular geometry and optical activity of N-nitroso-2,2,6,6-tetramethylpiperidines generated by spontaneous crystallization and inclusion complexation with optically active diols

Three sterically strained N-nitrosamines and their inclusion complexes with optically active diols (TADDOLs) were obtained and their solid state crystal structures are described. Owing to the formation of N-nitroso-4-hydroxy-2,2,6,6-tetramethylpiperidine 2 as spontaneously resolvable conglomerate crystals (space group P3₂) its solid state CD was measured. The crystal structures of the inclusion complexes revealed that in all cases the guest nitrosamines assume chiral conformations as seen by their chiroptical spectra. The optically active nitrosamines are configurationally labile and rapidly racemize in solution. The solid state structures revealed that in order to avoid an allylic 1,3-strain [A^(1,3)], caused by an interaction of the nitrosamino group with the methyl substituents, the piperidine ring in 1 and 2 assumes a chair conformation significantly flattened at the amino nitrogen whereas in the 4-oxo derivative 3 the piperidine ring assumes a twist-boat conformation.