Skip to main content
U.S. flag

An official website of the United States government

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

N-Nitrosation of Amines by NO2 and NO: A Theoretical Study

Published

Author(s)

Yi-Lei Zhao, Stephen L. Garrison, Carlos A. Gonzalez, William D. Thweatt, M Marquez

Abstract

Gas-phase nitrosation implies an alternative non-ionic pathway different from the nitrosonium-nitrosation by acidification of nitrite. Electronic structure calculations discussed in this work suggest a free radical mechanism, in which NO2 abstracts a hydrogen atom from nitrogen in primary and secondary amines to form an intermediate complex of an aminyl radical and nitrous acid. The aminyl radical intermediate is then quenched by nitric oxide, leading to the formation of nitrosamine. High-level calculations (CBS-QB3) showed that alkyl substitutions on amines can activate the H-abstraction reaction. Thus, while the H-abstraction from NH3 was found to exhibit a reaction barrier,??H?, of 106 kJ/mol, similar calculations indicate that the corresponding barriers in the case of methylamine and dimethylamine decrease to 72 and 45 kJ/mol, respectively. Heterocyclic secondary amines have been investigated in a similar manner; the 5-m-r amine appears the most reactive: aziridine (?H? = 74 kJ/mol), piperidine (?H? = 44 kJ/mol), azetidine (?H? = 44 kJ/mol), and pyrrolidine (?H? = 30 kJ/mol). The reaction barrier for 1H-pyrrole, an aromatic 5-m-r secondary amine, was found to be 59 kJ/mol. The origin of the high activity of the 5-m-r alkylamine stems from a hydrogen-bond-like interaction between the aminyl radical and the nascent nitrous acid molecule. This theoretical study suggests that, in the presence of nitrogen oxides, the gas-phase nitrosation of secondary amines is feasible.
Citation
Journal of Organic Chemistry
Volume
111
Issue
11

Keywords

Ab Initio, cancer, CBS-QB3, nitrosation, radical mechanism

Citation

Zhao, Y. , Garrison, S. , Gonzalez, C. , Thweatt, W. and Marquez, M. (2007), N-Nitrosation of Amines by NO<sub>2</sub> and NO: A Theoretical Study, Journal of Organic Chemistry (Accessed December 3, 2022)
Created March 22, 2007, Updated February 19, 2017