Nitrosation with nitrite ions

These results effectively exclude Kenner s suggestion that third-order nitrosation corresponds to slow proton loss from a tetrahedral intermediate (12), with nitrite ion acting as a base (Scheme 12). 

A similar mechanism was invoked by Ohshima and Kawabata (2) to account for their results in the nitrosation of tertiary amines and amine oxides. In applying these concepts to the nitrosative dealkylation of tetraalkyltetrazenes, Michejda al. 5) introduced an interesting variant by suggesting that immonium ions could be formed in two successive one-electron oxidation steps (for example by ferric ion oxidation of tertiary amine to the radical cation followed by radical abstraction of a hydrogen atom from the alpha position), rather than exclusively through the one-step removal of a hydride ion as nitroxyl. The resulting immonium ion was again considered to react directly with nitrite to produce the N-nitroso derivative. These reactions are summarized in Fig. 2b. 

Assuming that the above rationale for tertiary amine nitrosation was valid, we predicted 3) that the reaction of secondary amines with nitrite at milder pH s should be catalyzed by electrophilic carbonyl compounds, since secondary amines are known to form immonium ions on admixture with appropriate aldehydes and ketones. The prediction turned out to be true. Formaldehyde was shown to promote nitrosamine formation from a... 

The minor products frequendy formed in deaminations may result from such side reactions as reaction of the intermediate cation with nucleophiles, for example, acetate or chloride ions,49,30 present in low concentration. Nitrite ions can give rise to nitrite esters or ni-troalkanes 50,51 the former are probably hydrolyzed prior to or during processing of the products.52 Some alkenes have been reported to react with nitrous acid or related nitrosating agents.19,58 Enol ethers would be expected to be more nucleophilic than simple alkenes, and it has been found that D-glucal reacts with nitrous acid under the conditions of deamination.54... 

Reagents for amination, nitrosation and nitration of tertiary alkylamines are discussed in the appropriate reviews listed in Sections 6.1.3.1.4 and 6.I.3.I.5. Tertiary amines can be nitrosated with dealkylation by dinitrogen tetroxide for example, 1-methylpiperidine gave 1-nitrosopiperidine (80%). lliis reaction probably starts by one-electron oxidation of the amine, the aminium ion then undergoing dealkylation. Other oxidative d ylations and dealkylations include the formation of iV-nitrosodibenzylamine in high yield from the acid chloride (PhCH2)2NCOCl and sodium nitrite and the conversion of the amine (43) into the nitramine (44) with nitric acid. ... 

The Keefer-Roller nitrosation is not such as case, however, if one includes the mechanistic role of the catalyst, as shown in the sequence given in (4-9, R = H for formaldehyde). The aldehyde reacts first with the amine, forming an iminium ion. The Hard and Soft Acid and Base principle of Pearson (1963, 1968 Parr and Pearson, 1983 see also Zollinger, 1994, Sect. 3.2) predicts that the reaction of one of the O-atoms of the nitrite ion with the aldehyde C-atom of the iminium ion is the most likely reaction. In the last step, this addition product rearranges through an NN bonded four-membered ring transition state or intermediate into the nitrosoamine and the aldehyde. This mechanism is consistent with Casado s kinetic results. 

Covalent acyl nitrites formed from nitrous acid and various carboxylic acids react readily with aromatic amines, and they are used often for nitrosating water-insoluble amines . The mechanism must be similar to that for nitrous anhydride. In aqueous buffer solutions of carboxylic acids, however, the bulk of the reaction is brought about by nitrous anhydride itself. Acyl nitrites are formed, but these react more readily with the very basic nitrite ion, always present at pH > 3-5, than with tlae amine directly . ... 

Amino Acid and Carboxylato Complexes. Rate data for the formation kf) and dissociation (fcj of [Cr(X)Y] " ions from the reactions of [Cr(Y)(OH2)] "" " ions from the reactions of [Cr(Y)(OH2)] " ions H4Y = edta, H3Y = A-(hydroxyethyl)ethylenediamine-A, A, 7V -triacetic acid (hed-tra), ethylenediamine-N,A, A -triacetic acid (edtra), and A -methylethyl-enediamine-A,A, N -triacetic acid (medtra) with anions X" (NOi",Nf, NCS") are collected in Table 5.11. The accelerated rates of anation and aquation are ascribed to transient coordination of the pendant groups of ligands Y"". Nitrite ion probably reacts without Cr-0 bond fission in the case of [Cr(hedtra)(H20)]. However, for [Cr(medtra)(H20)] nitrosation proceeds via parallel reactions, one with and one without Cr-0 bond cleavage. 

A-Nitrosamines are formed by reaction of a secondary amine (or an amide containing a single N-H moiety) with a nitrosating agent, usually nitrite ion. Although such com-... 

The nitrosation of primary aromatic amines 1 with nitrous acid 2 and a subsequent dehydration step lead to the formation of diazonium ions 3. The unstable nitrous acid can for example be prepared by reaction of sodium nitrite with aqueous hydrochloric acid. 

The criteria for choosing inhibitors in this study were the ability to compete with diethanolamine for the nitrite and lack of toxicity. An attempt was made to cover as broad a group as possible within the limits of feasibility. Ascorbic acid in its water soluble form and its oil soluble form, the palmitate, represent the enediols, Sorbate is a diene fatty acid which has been shown to inhibit nitrosation (10), Since the pK of sorbic acid is 4,76, at the pH of these experiments, both water soluble sorbate ion and oil soluble sorbic acid are present in significant amounts. Sodium bisulfite is a strong inorganic reducing agent which has an acceptable lack of toxicity at the concentration... 

The fact that nitrite reacts with the iron of the heme compound was described earlier. Because such a large number of metal ions are present in meat, and because some occur in relatively high concentration, there has been considerable interest in them. For the most part, studies have dealt with how metal ions influence reactions of nitrite. The role of sodium chloride (which is used extensively in meat processing) must also be recognized both in terms of its functional role in making reactants in the meat more or less available, and in terms of reports that it directly influences nitrosation reactions (50). Ando (51) studied the effect of several metal ions on decomposition of nitrite, and in the absence of ascorbate, only Fe++ caused a loss of nitrite but in its presence, the effect of Fe " was more pronounced and Fe+++, Mg++, Ca++ and Zn++ showed similar effects. Lee e al. 

When thiocyanate ions are added to nitrous acid in water, a pink colouration develops which is believed to be due to the formation of nitrosyl thiocyanate (equation 34), which is too unstable to be isolated but which can be used as a nitrosating agent in aqueous solution. Because the equilibrium constant for ONSCN formation81 is quite large (30 dm6mol 2) at 25 °C, thiocyanate ion is an excellent catalyst for aqueous electrophilic nitrosation. The well established82 series is Cl- < Br < SCN < (NH2)2CS. Thiocyanate ion is also a sufficiently powerful nucleophile to react in acid solution with nitrosamines in a denitrosation process (equation 35), which can only be driven to the right if the nitrosyl thiocyanate is removed by, e.g., reaction with a nitrite trap such as hydrazoic acid. 

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