Nitrosamine anions

Another resonance-stabilized species discussed here is nitrosamine anions, whose chemistry has been reviewed several times.Cyclic nitrosamines normally lose the axial proton syn to the nitrosamine oxygen, and alkylate by axial approach of the electrophile. In these respects, nitrosamine anions are similar to their isoelectronic counterparts, oxime dianions, as shown in equation (4). ... 

The geometries of amide and nitrosamine anions differ in a fundamental way, and this difference has important implications for synthesis. Although cyclic nitrosamines lose the axial proton syn to the nitrosamine oxygen and alkylate by axial approach of the electrophile,cyclic amides lose the equatorial proton and alkylate equatorially" to give the thermodynamically less stable product, as illustrated in Scheme 2. 

Thus the nitrosamine anion is a resonance-stabilized species in which the carbanionic lone pair overlaps the TT-system of the nitrosamine. By contrast, the amide anion is a dipole-stabilized species in which the lone pair remains in or near the nodal plane of the amide n -system. Given the similarity of the two systems, this difference in behavior is striking. Although the geometry observed in nitrosamine anion alkylations is similar to that of their isoelectronic counterparts, oxime dianions,it is puzzling that amide anions differ, since they are also isoelectronic, as shown in Figure 1. 

Thiocyanate, an anion normally secreted in human saliva, also catalyzes the nitrosation of amines by nitrite (22). The mechanism of the reaction is thought to proceed through the formation of nitrosylthiocyanate and subsequent reaction with amine to form the nitrosamine. This reaction, originally investigated to assess the... 

Many activations involve compounds which are used as pesticides. In the case of N-nitrosation, the precursors are secondary amines and nitrate. The former are common synthetic compounds and the latter is an anion found in nearly all solid and aqueous phases. The N-nitrosation of a secondary amine [R-NH-R ] occurs in the presence of nitrite formed microbiologically from nitrate. The product is an N-nitroso compound (i.e., a nitrosamine [RR -N-N=0]). The reason for concern with nitrosamines is their potency, at low concentrations, as carcinogens, teratogens, and mutagens. 

In the presence of acetic acid, the radical-anion of a nitrosamine is protonated before bond cleavage can occur and further reactions give the dialkylhydrazine ... 

In acidic aqueous buffers, secondary nitramines [116] show a six-electron po-larographic wave which is converted into two two-electron waves above pH 5 (Fig. 11.4). Nitrosamines [117,118] show a four-electron wave in acid solution and this becomes a single two-electron wave above pH 5 (Fig, 11,5). Above pH 5 the halfwave potentials are independent of pH. Primary nitramines are relatively acidic. They show a six-electron wave in acidic aqueous buffers, the height of which falls to zero around the pKg value for the nitramine because the anion is not reducible [119],... 

An unique result of the electronic structure of the nitrosamine function is that it can apparently stabilize a positive or negative charge at the carbon adjacent to the amino nitrogen in a manner similar to the benzylic system. Hie stereoelectronic control of electroj ilic substitutions at the Or-position, to be discussed later, requires an orbital interaction of the nitrosamine function with the anionic electrons. Hie reactiv-... 

The procedure described here is an example of overall conversions by the nitrosamine method for the electrophilic substitution of 1 to 3 via the intermediate anion 2, as outlined in detail in a recent review article. ... 

The first edition of Food Analysis by HPLC fulfilled a need because no other book was available on all major topics of food compounds for the food analyst or engineer. In this second edition, completely revised chapters on amino acids, peptides, proteins, lipids, carbohydrates, vitamins, organic acids, organic bases, toxins, additives, antibacterials, pesticide residues, brewery products, nitrosamines, and anions and cations contain the most recent information on sample cleanup, derivatization, separation, and detection. New chapters have been added on alcohols, phenolic compounds, pigments, and residues of growth promoters. 

The formation of Af-nitrosamines which usually separate as orange-yellow oils or low melting solids indicates the presence of a secondary amine. Confirm the formation of the nitrosamine by the Liebermann nitroso reaction. This consists in warming the nitrosamine with phenol and concentrated sulphuric acid. The sulphuric acid liberates nitrous acid from the nitrosamine, and the nitrous acid reacts with the phenol to form p-nitrosophenol, which then combines with another molecule of phenol to give red indophenol. In alkaline solution the red indophenol yields a blue indophenol anion. 

Asymmetric Michael additions The anions of hydrazones (2), obtained from 1 and methyl ketones, undergo conjugate addition to a,p-unsaturated esters with virtually complete 1,6-asymmetric induction to give the adducts (S,R)-3. Ozonolysis converts these products into P-substituted 8-keto esters, (R)-4, obtained in optical yields of 96-l(X)%, with recovery of the chiral auxiliary as the nitrosamine (S)-5. The overall chemical yields of 4 are 45-62%. 

The acidity of hydrogoi atoms adjacent to the nitrogen substituent of N-nitrosamines has beat known for many years, although Seebach and cowoikers played a major role in developing this into a useful synthetic process. For exanqile, die anion of N-nitrosodimethylamine is formed by using LDA, and can be adulated or condoised with carbonyl compounds or nitriles (Scheme 2). l-Bromo-3-iodopropane... 

In alkaline solution most A-nitro derivatives of primary amines form an irreducible anion [R-bHSf02] , with nitraminopyridines as exceptions [205], whereas nitramines of secondary amines are reduced in two steps. [202]. The first reduction consumes 2F/mol and produces an A-nitrosamine. It is noteworthy that A-nitrosamines in alkaline solution are more difficult to reduce than the corresponding A-nitramines it seems to be the only class of nitro compounds in which the nitro group is more easily reducible than the nitroso group. 

Dipole-Stabilization is a term coined by Beak to describe the situation that results when a carbanion is stabilized by an adjacent dipole. Such a situation arises when, for example, an amide is deprotonated a to nitrogen. The chemistry of these systems has been reviewed, - so only a few pertinent points will be made here. Firstly, metalation occurs syn to the carbonyl oxygen, and when the system is cyclic, the equatorial proton is removed selectively, and the electrophile attacks equatorially, as shown in equation (5), 24, 25 Thus, in contrast to nitrosamines, amide anions give the less stable equatorial product. 4,i25... 

---