Nitrous acid reaction with bases

These reactions involve a diazonium ion (see 12-47) and are much faster than ordinary hydrolysis for benzamide the nitrous acid reaction took place 2.5 x lo times faster than ordinary hydrolysis. Another procedure for difficult cases involves treatment with aqueous sodium peroxide. In still another method, the amide is treated with water and f-BuOK at room temperature. " The strong base removes the proton from 107, thus preventing the reaction marked k j. A kinetic study has been done on the alkaline hydrolyses of A-trifluoroacetyl aniline derivatives. Amide hydrolysis can also be catalyzed by nucleophiles (see p. 427). 

Nevertheless, satisfactory results were often obtained in cyclizations through the azide. The method rests on the large difference in the rate of conversion of the hydrazide to the azide and that of deamination of the (protonated) N-ter-minal residue by nitrous acid. Hence, with the calculated amount of sodium nitrite (or alkyl nitrite) rapid conversion of the hydrazide to the azide can take place without significant deamination at the N-terminus. Cyclization occurs on addition of base that deprotonates the amino group and thus permits its acylation. This addition, however, should be preceded by dilution to decrease the extent of intermolecular reactions... 

The amino function in 4-amino-3-halopyridines belraves unexceptionally. Thus 4-amino-3-diloropyridine gives the 3-chloro-4-pyridinediazonium salt dien treated with nitrous acid the diazonium salt decomposes in the presence of potassium iodide to yield 3-chloro-4-iodopyridine. 4-Amino-2,3,5,6-tetrafluoropyridine is a very weak base but it can be diazotized in 80% hydrofluoric acid. The diazonium salt is converted to 4-bromo-2,3,5,6-tetrabromopyridine with cuprous bromide, but its reaction with water or with A, lV-dimethylaniline are complex. 4-Amino-2-chloro-3-nitropyridine is not converted to 2-chloro-3-nitro-4-pyridone (K-97) on diazotization with mineral acids and sodium nitrite or with isoamyl nitrite in glacial acetic acid with the latter reagent 2-chloro-3-nitropyri-dine (K-98) is formed." Nitrous acid reacts with 4-amlno-2-pyridone to give 4-amino-3-nitroso-2-pyridone instead of the diazonium salt. ... 

The colorations produced in this reaction arise from the action of nitrous acid on the phenol, giving />-nitrosophenol (I) which then reacts with excess of phenol to form an indophenol (II) which is an acid-base indicator ... 

Cycloaliphatic amines are strong bases with chemistry similar to that of simpler primary, secondary, or tertiary amines. Upon reaction with nitrous acid,... 

The mechanism is presumed to involve a pathway related to those proposed for other base-catalyzed reactions of isocyanoacetates with Michael acceptors. Thus base-induced formation of enolate 9 is followed by Michael addition to the nitroalkene and cyclization of nitronate 10 to furnish 11 after protonation. Loss of nitrous acid and aromatization affords pyrrole ester 12. 

Hydrolyses of aminopyridopyrimidines to the corresponding pyridopyrimidones by means of acid, base, and nitrous acid have been reported. 4-Amino compounds are stable to nitrous acid, but are much more labile than the 2-amino derivatives toward acid- or base-catalyzed hydrolysis. The aminochloro-pyrido[2,3-d]pyrimidine (160) has been converted into the 2,4-dianilino analog (161) by reaction with aniline." ... 

It has already been pointed out that nitrosation is probably the first step in diazotization. Ingold (1952) describes the reaction as N-nitrosation and classifies it as an electrophilic substitution, together with related processes such as the formation of 4-nitrosophenol, an example of a C-nitrosation. It was probably Adamson and Kenner (1934) who first applied these ideas to diazotization and realized that in aniline itself the electron density at the nitrogen atom is greater than in the anilinium ion, so that the base is more reactive. On the other hand, the nitrosoacidium ion (3.1), the addition product of nitrous acid and a proton, is a more powerful electrophilic reagent than the HN02 molecule. They therefore represented the first step of diazotization as in Scheme 3-5. 

Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%)." In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

The tertiary aromatic bases share with the phenols the property of taking up a nitroso-group in the p-position when treated with nitrous acid in acid solution. As was mentioned elsewhere (p. 307), this reaction may be compared to the coupling of these compounds with diazobenzene. 

Theory The estimation is based on the fact that isocarboxazid undergoes rapid cleavage in acidic medium to produce benzylhydrazine. The latter reacts quantitatively with nitrous acid (NaN02 and HC1) to give rise to benzylazide. The various reactions involved are expressed as follows ... 

Diazo esters can also be prepared from glycine esters by treatment with nitrous acid [966] or with alkyl nitrites. Further methods include the oxidation of hydrazones, oximes (Forster reaction), and semicarbazones, the base-induced... 

Cytosine can become deaminated spontaneously or by reaction with nitrous acid to form uracil. This leaves an improper base pair (G-U), which is eliminated by a base excision repair mechanism (Figure 1-2-5). Failure to repair the improper base pair can convert a normal G-C pair to an A-T pair. 

Photolytic. Synthetic air containing gaseous nitrous acid and exposed to artificial sunlight (A, = 300-450 nm) photooxidized 2-butanone into peroxyacetyl nitrate and methyl nitrate (Cox et al., 1980). They reported a rate constant of 2.6 x 10 cm /molecule-sec for the reaction of gaseous 2-butane with OH radicals based on a value of 8 x 10 cm /molecule-sec for the reaction of ethylene with OH radicals. 

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