Chapter 26
Radical Cations in Nitrosation of tert-Dialkyl Aromatic Amines S. Singh, R. Hastings, and Richard N. Loeppky
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Department of Chemistry, University of Missouri, Columbia, MO 65211
Ν,Ν-Dialkylaromatic amines react surprisingly rapidly with nitrous acid to pro duce a nitrosamine and a nitro compound as shown in Scheme 1. At 25º C thet of 0.19 mM N,N-dimethyl-4-chloroaniline (DMCA) in 1.9 mM HNO (pH 3. + -7) is 8 mi and that of the 4-carboethoxy analog (0.068 M) is 110 min. Most trialkyl amines undergo nitrosative dealkyation at very slow rates at 25º (1,2). To determine if the more rapid reaction of Ν,Ν-dialkylaromatic amines could be due to their lower basi city, which permit higher concentrations of the key nitrosammonium ion intermediate, we nitrosated N(CH CH OMe) and DMCA under conditions where the free amine concentrations were equal. It was found that DMCA nitrosated about 40 times faster. These data suggest that a new mechanism may be operative for aromatic dialkyl amines. The concurrent formation of an aromatic nitro compound in these nitrosative dealkylation reactions suggests that a radical cation may be a reaction intermediate, because considerable data has recently been amassed to support radical cation involve ment in nitration, and nitrite catalyzed nitration reactions of electron-rich aromatic 1/2
2
2
2
3
systems (3,4). Scheme 1 illustrates our mechanistic hypothesis which also allows for the formation of the nitrosamine by two routes, the classical mechanism (1) and another. Proof of a radical intermediate in the formation of the nitro compound was obtained from CIDNP N NMR experiments. The nitro compound gave an enhanced emission signal {3) when the nitrosation of DMCA was done with Na N0 . The nitro compound could form from the radical cation either by direct reaction with N 0 produced from the decomposition of N 0 , or by its reaction with N 0 - fol lowed by rapid oxidation. Reaction of the stable radical cation of Ν,Ν,Ν',Ν'tetramethyl-p-phenylenediamine (Wurster's blue) with aqueous NaN0 gave only a 2% yield of the nitro compound (Scheme 2) but a 72% yield of the nitrosamine. These data suggest that the nitro compound arises from N 0 not N 0 - and also show that the nitrosamine can arise from a radical cation. The radical cation could be produced either from a homolytic dissociation of N-nitrosammonium ion or through an electron transfer reaction with an N O donor (3,4). 1 5
15
2
1 5
2
2
3
2
2
2
2
+
0097-6156/94/0553-0309$08.00/0 © 1994 American Chemical Society
In Nitrosamines and Related N-Nitroso Compounds; Loeppky, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
310
NTTROSAMINES AND RELATED iV-NITROSO COMPOUNDS 2HN0 ^===: N 0 2
N 0 2
2
* ·N0
3
3
2
+ +
H 0 2
NO
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NO
Scheme 1 CIDNP emission is not observed for the nitrosamine and is not expected because its immediate precursors are not radicals. The work of Dinocenzo (5) suggests that the nitrosamine arises from the radical cation by loss of a proton in the rate determining step to generate an α-amino nitrite ester which rapidly gives the nitrosam ine (6). While this pathway is supported by out data and a deuterium isotope effect of 8.2 for the nitrosation of DMCA, we also observe the formation of N 0 which is formed in the classical mechanism from NOH eliminated by nitrosammonium ion. Other experimental data derived from the nitrosation of 4-carboethoxy-N,Ndimethylaniline show that the k /k values change with conditions suggesting that competing mechanisms are operative. Additional evidence in support of the competi tive mechanism comes form the observation that the methyl vs. ethyl cleavage ethly ratios produced from the nitrosation of N-ethyl-N-methyl-4-carboethoxyaniline are time dependent. 2
H
D
In Nitrosamines and Related N-Nitroso Compounds; Loeppky, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
26.
Nitrosation of tert-Dialkyl Aromatic Amines
SINGH E T A L
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Downloaded by EAST CAROLINA UNIV on August 5, 2013 | http://pubs.acs.org Publication Date: March 28, 1994 | doi: 10.1021/bk-1994-0553.ch026
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+
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Scheme 2 Acknowledgement The support of this research by grant R37 CA26914 from the National Cancer Insti tute is gratefully acknowledged. References (1) Smith, P. A. S.; Loeppky, R. N. J. Am. Chem. Soc. 1967, 89, 1147-1157. (2) Gowenlock, B.; Hutcheson, R. J.; Little, J.; Pfab, J.J. Chem. Soc. Perkin. Trans. II. 1979, 1110-1114. (3) Clemens, A. H.; Helsby, P.; Ridd, J. H.; Omran, F. A. J. Chem. Soc. Perkin. Trans. II. 1985, 1217. (4) Kochi, J.K.Acc. Chem. Res. 1992, 25, 39. (5) Dinocenzo, J. P.; and Banach, T. E. J. Am. Chem. Soc. 1989, 111, 8646. (6) Keefer, L. K.; Roller, P. P. Science. 1973, 181, 1245. R E C E I V E D November 15,
1993
In Nitrosamines and Related N-Nitroso Compounds; Loeppky, R., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1994.
