Nitrosation of Alkylamines

When solutions of sodium nitrite (NaN02) are acidified, a number of species are formed that act as nitrosating agents. That is, they react as sources of nitrosyl cation, = N=0 =. In order to simplify discussion, organic chemists group all these species together and speak of the chemistry of one of them, nitrous acid, as a generalized precursor to nitrosyl cation. 

Nitrosation of amines is best illustrated by examining what happens when a secondary amine reacts with nitrous acid. The amine acts as a nucleophile, attacking the nitrogen of nitrosyl cation. 

The intermediate that is formed in the first step loses a proton to give an A -nitroso amine as the isolated product. 

PROBLEM 22.15 A/-Nitroso amines are stabilized by electron delocalization. Write the two most stable resonance forms of W-nitrosodimethylamine, (CH3)2NN0. 

A-Nitrosodimethylamine (formed during tanning of leather also found in beer and herbicides) 

A -Nitroso amines are more often called nitrosamines, and because many of them are potent carcinogens, they have been the object of much recent investigation. We encounter nitrosamines in the environment on a daily basis. A few of these, all of which are known carcinogens, are  

When solutions of sodium nitrite (NaN02) are acidified, a number of species are formed 

Decreasing the electron-donating ability of an amino group by acylation makes monohalo- 

Friedel-Crafts reactions are normally not successful when attempted on an arylamine, but can be carried out readily once the amino group is protected. 

Nitrosyl cation is also called nitrosonium ion. It can be represented by the two resonance structures 

Diazo Chemistry II Aliphatic, Inorganic and Organometallic Compounds. By Heinrich Zollinger Copyright 1995 VCH Verlagsgesellschail mbH ISBN 3-527-29222-5 

Secondary aliphatic amines form stable N-nitrosoamines, however, and therefore, their investigation will be discussed briefly in this section, although N-nitroso derivatives of secondary aliphatic amines do not fall within the scope of this book. We will see that kinetics and mechanisms of nitrosation of secondary amines display many similarities with the diazotization of primary aromatic amines. 

It must also be emphasized, however, that these calculations of intrinsic rate constants for the reaction step ONX + R2NH (X = ONO or halogens) are directly dependent on the numerical value of the equilibrium constants onx- The accurate determination of these constants is experimentally difficult, as shown for N203- earlier measurements by Stedman (1979) gave a value of ca. 2.1 x 10 whereas more recent determinations resulted in n20s = 3.0 x 10 et al., 1981). 

Catalysis by other nucleophiles has also been found for secondary aliphatic amines, e. g., by thiocyanate (Fan and Tannenbaum, 1973), and by thiourea and its tetramethyl derivative (Meyer and Williams, 1988, and earlier investigations mentioned there). The results are comparable to those of aromatic diazotizations (Zollinger, 1994, Sect. 3.3). 

The rate of nitrosation of long-chain amines increases if the critical micelle concentration is exceeded (Moss et al., 1973a). 

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Even in series of nitrosations of alkylamines with electron-withdrawing substituents, such discrepancies between comparable compounds are known. Thus, Gilman and Jones (1943) found 70% of l-diazo-2,2,2-trifluoroethane in the reaction of 2,2,2-trifluoroethylamine, HCl, and NaN02. This result was confirmed by Dyatkin and Mochalina (1964). Nevertheless, Atherton et al. (1971) were unable to synthesize l-diazo-2,2-difluoroethane by nitrosation of 2,2-difluoroethylamine and with 2,2,3,3-tetrafluoropropylamine they obtained a yield of only 10%. Good yields are reported, however, for the diazotization of the fluorinated aminoalkane 2.21 (Coe et al., 1983) and of 2-amino-l,l,l-trifluoro-3-nitro-propane (2.22, Aizikovich and Bazyl, 1987). Jin et al. (1992) claim that l-diazo-2,2,2-trifluoroethane can be ob-... 

Attention towards an aliphatic diazonium ion as a transient intermediate in nitrosation of alkylamines was subsequently further distracted by investigations of Linnemann and Siersch (1867), who found that in the reaction of propylamine even more propan-2-ol was detected than the propan-l-ol expected. Kinetics of nitrosa-tions of alkylamines were determined as early as 1928 by Taylor, but it was not until Hammett, in his pioneering book on physical organic chemistry (1940, p. 295), that the analogy to the aromatic series was established. He suggested that diazonium ions are also intermediates in the reactions of aliphatic primary amines. 

Another important diazotization method is the use of glacial acid for the nitrosation of alkylamines, because of the formation of an ion pair 7.12 between the acetate ion and the diazonium ion. In water the influence of acetate ion is small. 

N-Nitroso amides can also be used for the formation of alkyldiazenolates (7.9) by bases. Alkyldiazenolates can be isolated from aprotic solvents as alkali metal salts, as found by Hantzsch and Lehmann (1902). More modern procedures have been described by Tandy and Jones (1965) and by Moss (1966). One obtaines the (Z)-diazenolate, as confirmed by X-ray analysis (Muller et al., 1963). From Scheme 7-3, one might assume that the route starting with diazenolates will lead to the same products as the nitrosation of alkylamines because the diazenol is common for both pathways. 

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