Nitrosation of secondary

Some recent general reviews deal with the mechanism of N-nitrosation in aqueous solution (345), the nitrosation of secondary amines (346). the effect of solvent acidity On diazotization (347) and the reactivity of diazonium salts (1691). Therefore, a complete rationalization of the reactivity of amino azaaromatics would be timelv. 

W-Nitroso amine (Section 22.15) A compound of the type R,N—N=0. R may be alkyl or aryl groups, which may be the same or different. A-Nitroso amines are formed by nitrosation of secondary amines. 

Research into the mechanism of diazotization was based on Bamberger s supposition (1894 b) that the reaction corresponds to the formation of A-nitroso-A-alkyl-arylamines. The TV-nitrosation of secondary amines finishes at the nitrosoamine stage (because protolysis is not possible), but primary nitrosoamines are quickly transformed into diazo compounds in a moderately to strongly acidic medium. The process probably takes place by a prototropic rearrangement to the diazohydroxide, which is then attacked by a hydroxonium ion to yield the diazonium salt (Scheme 3-1 see also Sec. 3.4). 

Schmolukowski in 1917, a diffusion-controlled bimolecular reaction in solution at 25 °C can reach a value for th second-order rate constant k as high as 7 x 109 m 1s-1. Nitrosations of secondary aliphatic amines also have rates which are relatively close to diffusion control (see Zollinger, 1995, Sec. 4.1). 

It is appropriate to add here some comments on diazotization in anhydrous carboxylic acids. They may be relevant for the diazotization of heteroaromatic amines carried out in acetic acid/propionic acid mixtures (Sec. 2.2). Extensive studies by Casado et al. (1983, 1984) showed that in nitrosation of secondary amines the nitrosyl ion, nitrosyl acetate, and dinitrogen trioxide are formed, and all three may act as nitrosating agents. The results do not, however, account for the considerable improvement that is claimed in the patent literature (Weaver and Shuttleworth, 1982) to result from the addition of carboxylic acids in the diazotization of heteroaromatic amines. 

We thus assume, that the biochemical processes during tobacco curing may be different from the ui vitro N-nitrosation of secondary and tertiary amines (30). 

TABLE III. Kinetic Data for Nitrosation of Secondary Amino Acids at pH 2.5... 

This relationship, studies less than that of nitrosamines and microorganisms, offers similar possibilities. Plants could presumably affect nitrosation of secondary amines under certain... 

Scheme 8.4 Nitrosation of secondary amines from NONOates.

Many different pathways, mechanisms, and enzymes are associated with activation. These include dehalogenation, AT-nitrosation of secondary amines, epoxidation, conversion of phosphothionates to phosphate, metabolism of phen-oxyalkanoic acids, oxidation of thioethers, hydrolysis of esters and peroxides. The following is a summary. 

The nitrosation of secondary amines with sodium nitrite in the presence of acids is by far still the most widely used method for the preparation of N-nitrosamines. Several variations of this... 

One of the best-knbwn methods for the preparation of aromatic nitroso compounds is the Fischer-Hepp rearrangement of A-nitrosoamines (Eq. 2). In effect, this reaction is the C-nitrosation of secondary aromatic amines. 

The nitrosation of secondary aliphatic amines with sodium nitrite and hydrochloric acid has been well described [18b]. 

Nitrosylhaems are readily formed from nitric oxide and haems and appear again to be carriers of NO which can effect nitrosation of secondary amines (Bonnett et a .. 1975). The structure of the nitrosylhaems was confirmed by their esr spectra, including those obtained by direct examination of a variety of cured meats (Bonnett et al., 1980). 

The nitrosation of secondary amines is reversible in acid solution, so A-nitrosamines may be hydrolized at low pH. Such hydrolysis is especially important for diaryl nitrosamines but also significant for aryl akyl nitrosamines. The NO liberated in the hydrolysis may react with the reduction product from the A-nitrosamine, the unsymmetrical hydrazine, with formation of amine and N2O [213,214] ... 

As is known, pseudonitroles are formed by nitrosation of secondary nttro-... 

Ascorbic acid is known to inhibit the nitrosation of secondary amines. A computer model has been developed to predict the amount of nitrosamine formed under conditions that are experimentally inaccessible. The computer-calculated rates for N-nitrosomorpholine formation using rate and equilibrium constants from the literature agree well with experimental values in the absence of and presence of ascorbic acid under anaerobic conditions. In the aerobic system the inhibitory efficiency of ascorbic acid is lower, and the nature of the interactions among the various components of the mixtures is less well understood. The use of ascorbic acid for inhibition of N-nitroso compound formation both in vitro and in vivo is briefly reviewed. 

Figure 18. The proposed mechanism of nitrosation of secondary amides by encapsulated calixarene-based reagents. The dimensions of R groups of substrate are critical and control the formation of the corresponding O-nitroso intermediate.

Mono-A-nitrosation of 1,2-dialkylhydrazines can be effected in the same way as nitrosation of secondary amines. For instance, 1,2-diisopropyl-1-nitrosohydrazine is obtained by using sodium nitrite in either glacial acetic or hydrochloric acid.222... 

Nitrosation. Nitrosation of secondary amines and thiols under heterogeneous conditions uses NaN02-oxalic acid in dichloromethane and r-butanol, respectively. 

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