Nitrosic acid

Nitrosic acid, HsN206. Nitrogen peroxide, N204. 

We are not concerned here with the mechanism of nitrosation, but with the anticatalytic effect of nitrous acid upon nitration, and with the way in which this is superseded with very reactive compounds by an indirect mechanism for nitration. The term nitrous acid indicates all the species in a solution which, after dilution with water, can be estimated as nitrous acid. 

The theory that the catalysed nitration proceeds through nitrosation was supported by the isolation of some />-nitrosophenol from the interrupted nitration of phenol, and from the observation that the ortho.-para ratio (9 91) of strongly catalysed nitration under aqueous conditions was very similar to the corresponding ratio of formation of nitrosophenols in the absence of nitric acid. ... 

Nitration at the encounter rate and nitrosation As has been seen ( 3.3), the rate of nitration by solutions of nitric acid in nitromethane or sulpholan reaches a limit for activated compounds which is about 300 times the rate for benzene imder the same conditions. Under the conditions of first-order nitration (7-5 % aqueous sulpholan) mesitylene reacts at this limiting rate, and its nitration is not subject to catalysis by nitrous acid thus, mesitylene is nitrated by nitronium ions at the encounter rate, and under these conditions is not subject to nitration via nitrosation. The significance of nitration at the encounter rate for mechanistic studies has been discussed ( 2.5). 

Under the conditions mentioned, i-methylnaphthalene was nitrated appreciably faster than was mesitylene, and the nitration was strongly catalysed by nitrous acid. The mere fact of reaction at a rate greater than the encounter rate demonstrates the incursion of a new mechanism of nitration, and its characteristics identify it as nitration via nitrosation. 

Under the same conditions the even more reactive compounds 1,6-dimethylnaphthalene, phenol, and wt-cresol were nitrated very rapidly by an autocatalytic process [nitrous acid being generated in the way already discussed ( 4.3.3)]. However, by adding urea to the solutions the autocatalytic reaction could be suppressed, and 1,6-dimethyl-naphthalene and phenol were found to be nitrated about 700 times faster than benzene. Again, the barrier of the encounter rate of reaction with nitronium ions was broken, and the occurrence of nitration by the special mechanism, via nitrosation, demonstrated. 

The evidence outlined strongly suggests that nitration via nitrosation accompanies the general mechanism of nitration in these media in the reactions of very reactive compounds.i Proof that phenol, even in solutions prepared from pure nitric acid, underwent nitration by a special mechanism came from examining rates of reaction of phenol and mesi-tylene under zeroth-order conditions. The variation in the initial rates with the concentration of aromatic (fig. 5.2) shows that mesitylene (o-2-0 4 mol 1 ) reacts at the zeroth-order rate, whereas phenol is nitrated considerably faster by a process which is first order in the concentration of aromatic. It is noteworthy that in these solutions the concentration of nitrous acid was below the level of detection (< c. 5 X mol... 

Without further studies little weight can be given to these ideas. In particular there is the possibility that with acetanilide, as with anisole, nitrosation is of some importance, and further with nitrations in sulphuric acid the effect of protonation of the substrate needs quantitative evaluation. The possibility that the latter factor may be important has been recognised, and it may account for the difference between nitration in sulphuric acid and nitration with nitronium tetrafluoroborate. 

Phenol. The change in the orientation of substitution into phenol as a result of the superimposition of nitrosation on nitration is a well-established phenomenon. In aqueous sulphuric acid it leads to a change from the production of 73 % of o-nitrophenol under nitrating... 

Thus, strong arguments against all of the obvious nitrating species acting alone can be found. However, as has been pointed out, the extent to which ions require solvation by nitric acid molecules in this medium is unknown, and such solvation would influence the apparent order with respect to the stoichiometric nitric acid. The possibility also exists that more than one mechanism of nitration, excluding nitrosation, is operative. 

Butler recently reviewed the diazotization of heterocyclic amines (317). Reactions with nitrous acid yield in most cases N-exocyclic compounds. Since tertiary amines are usually regarded as inen to nitrosation, this... 

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. 

Nitrosation of amines is best illustrated by examining what happens when a sec ondary amine reacts with nitrous acid The amine acts as a nucleophile attacking the nitrogen of nitrosyl cation The intermediate that is formed m the first step loses a pro ton to give an N nitroso amine as the isolated product... 

Nitrosation (Section 22 15) Nitrosation of amines occurs when sodium nitrite is added to a solution containing an amine and an acid Primary amines y e d alkyl diazonium salts Alkyl diazonium salts are very unstable and yield carbo cation derived products Aryl diazonium salts are exceedingly useful synthetic in termediates Their reactions are de scribed in Table 22 7... 

Nitrosation (Section 22 15) The reaction of a substance usu ally an amine with nitrous acid Pnmary amines yield dia zonium 10ns secondary amines yield N nitroso amines Tertiary aromatic amines undergo nitrosation of their aro matic ring... 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availabiUty of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-cataly2ed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

Manufacture of 3-hydroxy-4-amino-l-naphthalenesulfonic acid involves the nitrosation of 2-naphthalenol, bisulfite addition, and reduction of the nitroso to the amino group by sulfur dioxide generated in situ (47). 3-Hydroxy-4-amino-l-naphthalenesulfonic acid is obtained in 80% yield. 

By the nitrosation of 2-naphthalenol and the reaction of the nitroso compound with sodium bisulfite. By nitrosation/reduction of 6-hydroxy-2-naphthalenesulfonic acid. 

Synthesis. The classic laboratory synthesis of /V-nitrosamines is the reaction of a secondary amine with acidic nitrite [14797-65-0] at ca pH 3. The primary nitrosating intermediate is N2O2 arising from nitrous acid [7782-77-6] (48). 

Inhibition of nitrosation is generally accompHshed by substances that compete effectively for the active nitrosating iatermediate. /V-Nitrosamine formation in vitro can be inhibited by ascorbic acid [50-81-7] (vitamin C) and a-tocopherol [59-02-9] (vitamin E) (61,62), as well as by several other classes of compounds including pyrroles, phenols, and a2iridines (63—65). Inhibition of iatragastric nitrosation ia humans by ascorbic acid and by foods such as fmit and vegetable juices or food extracts has been reported ia several instances (26,66,67). 

Sodium Bisulfite. Sodium bisulfite [7631-90-5] NaHSO, is occasionally used to perform simultaneous reduction of a nitro group to an amine and the addition of a sulfonic acid group. For example, 4-amino-3-hydroxyl-l-naphthalenesulfonic acid [116-63-2] C qH NO S, is manufactured from 2-naphthol in a process which uses sodium bisulfite (59). The process involves nitrosation of 2-naphthol in aqueous medium, followed by addition of sodium bisulfite and acidification with sulfuric acid. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Retarders were originally arenecarboxylic acids. These acidic materials not only delay the onset of cross-linking but also slow the cross-linking reaction itself. The acidic retarders do not function weU in black-fiUed compounds because of the high pH of furnace blacks. Another type of retarder, A/-nitroso diphenylamine [86-30-6] was used for many years in black-fiUed compounds. This product disappeared when it was recognized that it trans-nitrosated volatile amines to give a several-fold increase in airborne nitrosamines. U.S. production peaked in 1974 at about 1.6 million kg. 

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