Reactions with Nitrite

Although the reaction of nitrous acid with peptides and proteins has been extensively used for analytical purposes (van Slyke estimation), the nature of the organic products has often been overlooked. Recently, Bonnett and Holleyhead 49) reported that treatment of N-acyl-tryptophan derivatives with sodium nitrite under mildly acidic conditions furnishes nitrosamines with the nitroso group located at the indolic nitrogen. 

The reaction takes place smoothly in about 50% yield in aqueous acetic acid at room temperature with simple tryptophan derivatives and also with tryptophan peptides. The N-nitrosamine bond in the tryptophan derivatives is cleaved by mineral acids, such as HBr in acetic acid. The derivatives are also photolabile, so that the electronic spectra cannot be measured accurately. 

Nitrosation of the indole nucleus was found to be a drawback in the synthesis of tryptophan peptides when the azide coupling procedure was used (see Section VI. 1. for more details). The nitrosation reaction has been also found useful in devising an analytical method for determination of tryptophan and related indole compounds (see Section IV.6.). 

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Analytical and Laboratory Operations. Sulfamic acid has been recommended as a reference standard in acidimetry (55). It can be purified by recrystaUization to give a stable product that is 99.95 wt % pure. The reaction with nitrite as used in the sulfamic acid analytical method has also been adapted for determination of nitrites with the acid as the reagent. This reaction is used commercially in other systems for removal of nitrous acid impurities, eg, in sulfuric and hydrochloric acid purification operations. 

The reaction with nitrite proceeds smoothly and with relatively high yields of the corresponding nitroarene (see Sec. 10.6). Obviously a major part of the driving force of this reaction is the formation of a stable, i. e., an energetically favorable, radical, nitrogen dioxide. With the hydroxide ion — a much stronger nucleophile than the nitrite ion — the reaction is expected to produce very unstable radicals, the hydroxy radical OH and the oxygen radical anion O, from the diazohydroxide (Ar - N2 — OH) and the diazoate (Ar-N20 ) respectively. Consequently, dediazoniation in alkaline aqueous solution does not follow the simple Scheme 8-41 with Yn = OH, but instead involves diazoanhydrides (Ar — N2 —O —N2 —Ar) as intermediates (see Sec. 8.8). 

Besada [12] described a spectrophotometric method for determination of penicillamine by reaction with nitrite and Co(II). Penicillamine is first treated with 1 M NaN02 (to convert the amino-group into a hydroxy-group), then with 0.1 M CoCl2, and finally the absorbance of the brownish-yellow complex obtained is measured at 250 nm. The process is carried out in 50% aqueous ethanol, and the pH is adjusted to 5.4— 6.5 for maximum absorbance. The calibration graph is linear over the concentration range of 0.25-2.5 mg per 50 mL, and the mean recovery (n = 3) of added drug is 99.7%. Cystine, cysteine, methionine, and other amino adds do not interfere. 

Albert, R. Dax, K. Link, R. W. Stutz, A. E., Carbohydrate Triflates - Reaction with Nitrite, Leading Directly to Epi-Hydroxy Compounds. Carbohydr. Res. 1983, 118, C5-C6. 

The only reactions of 2-diazobenzimidazole with nucleophiles involved the coupling with a-chloro-dicarbonyl compounds that gave the chlorohy-drazones (82MI2) and the reaction with nitrite in the presence of copper sulfate which led to the 2-nitrobenzimidazole (65AAC469). 

Thanks are due to the Editor of this volume for suggesting the similarity of N,N-disubstituted carbamoyl nitrites to the a-amino nitrite esters discussed above. When N,N-diphenyl carbamoyl chloride was refluxed with sodium nitrite in acetonitrile solution for 24 hours, N-nitrosodiphenylamine was produced in quantitative yield (M. Nakajima and J.-P. Anselme, unpublished results). The N,N-dibenzyl derivative underwent a similar reaction with nitrite. The mechanism shown in Fig. 13 was postulated to account for these transformations. 

Other, more sensitive, tests have been suggested for the evaluation of potential carcinogenic risk of exposure to chemicals. These include the bacterial mutagenesis test devised by Dr. Bruce Ames ( ). This test has been applied to many of the amines listed in Table 1, both alone and after reaction with nitrite in weakly acid solution, followed by neutralization and application to the bacteria. In Table 3 are given the results of a number of such tests, together with comparison of the results of chronic... 

LeGall, J., Payne, W. J., Morgan, T. V., and DerVartanian, D. (1979). On the purification of nitrite reductase from Thiobacillus denitrificans and its reaction with nitrite under reducing conditions. Biochem. Biophys. Res. Commun. 87, 355-362. 

Nitrite complexes of platinum can be formed, and complexes are known where the N02 ligand is N- or O-bonded. For platinum(II) the compounds are N-bonded, but for platinum(IV) complexes can be synthesized which are O- or N-bonded. Synthetic methods involve substitution reactions with nitrite ion or addition of NO to Pt02(PPh3)2 (equations 477 and... 

The mechanism of the reaction of [Fe2(SR)2(CO)6] with nitric oxide does not seem to have been investigated. The corresponding reaction with nitrite in DMF proceeds (25) via the mononuclear complex [Fe(NO)2(SR)2] (see Section II,B,1), but it is not yet known how this complex is formed from [Fe2(SR)2(CO)6],... 

Displacement reactions with nitrite ion do not work well with aryl halides. However, displacement of the diazonium group is a practical route to nitroarenes (the Sandmeyer reaction), as described in Section 23-10B ... 

Local nitrite concentrations in tissues are linked to the amounts of NO produced. Indeed, except for nitrate generated from the reaction of NO with oxyHb, nitrite is the major end product of NO metabolism. Increased nitrite levels are thus found under pathophysiological conditions, for example inflammation, when N O production is elevated. We have found that the rate constants for the reactions of the ferryl forms of Mb and Hb with nitrite are significantly lower than those for the corresponding reaction with NO (16 + 1 m 1 s 1 at pH 7.5 for Mb and (7.5 + 0.1) x 102 m 1 s 1 at pH 7.0 for Hb, at 20 °C) [19, 20]. Thus, the reaction with nitrite probably plays a role only when NO has been consumed completely and large concentrations of nitrite are still present. 

Azides are formed by the reaction of lithio derivatives with />-toliicncsulfonyl azide, and these in turn can be converted into the corresponding amino compounds by a variety of reductive procedures. Nitro compounds are available by a novel reversal of the general pattern of reaction with electrophiles. This approach requires the initial conversion of the lithio compound into an iodonium salt followed by reaction with nitrite ion. This is illustrated by the preparation of 3-nitrothiophene (Scheme 145). Other nucleophiles, such as thiocyanate ion which yields the 3-thiocyanate, can be employed. The preparative significance of these reactions is again that products not accessible by electrophilic substitution can be obtained. 

Reaction with nitrite anion 5,7.2.3.3 C3H,CIMg i-C3H,MgCl... 

The reactions of alkyl sulfonates with superoxide ion and with nitrite ion directly afford the corresponding inverted alcohols. - Although displacement by superoxide ion has been successfully utilized in prostaglandin chemistry, elimination again takes place to some extent, depending on the structures of the substrates. In the reaction with nitrite ion, ketone and nitroalkane are also formed. The inversion of cyclopentanol derivatives via tosylates has been studied by the use of various methods involving displacement by benzoate, nitrite ion and superoxide ion as well as the diethyl azodicarboxylate (DEAD)-PhsP procedure, where varied amounts of elimination products are invariably formed. ... 

B. to remove any sulfate ions existing prior to the reaction with nitrite... 

Yoshida, D. and T. Matsumoto Changes in mutagenicity of protein pyrolyzates by reaction with nitrite Mntation Res. 58 (1978) 35. ... 

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