4- Nitrosophenol, formation

FIGURE 3 4-Nitrosophenol formation from the reaction of peroxynitrite (ONOO ), nitric oxide (NO), or both (added simultaneously) with phenol at pH 6.0, 7.4, and 8.0. All reactions contained 2 mM phenol and 0.1 mM DTPA (to minimize redox-active metals) in a final volume of 2 ml of 0.1 M potassium phosphate at the indicated pH at 37"C. ONOO", nitric oxide (210 jU.1 of 1.9 mM solution), or both were added simultaneously to rapidly stuxed solutions. The final pH was measured. Reaction products were measured by high-performance liquid chromatography (8-cm C-18, 100 mM ammonium formate, pH 3.5, linear gradient from 5% to 80% acetonitrile over 10 min). Detection at 280 and 365 nm (nitroso and nitro adducts absorb at 365 nm) was used to identify and quantify reaction products relative to authentic standards. 

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. ... 

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. 

Smoking. The effects of smoking on the formation of N-nitros-amines in bacon has been investigated recently by Bharucha et al. ( ). They reported that unsmoked bacon samples generally tended to contain more N-nitrosamines, presumably because of their higher nitrite content at the time of frying. Sink and Hsu (55) showed a lowering of residual nitrite in a liquid smoke dip process for frankfurters when the pH also was lowered. The effects of smoke seem to be a combination of pH decrease and direct C-nitrosation of phenolic compounds to lower the residual nitrite in the product (56). This is an area which requires further study since certain C-nitrosophenols have been shown to catalytically transnitrosate amines in model systems (57). 

The nitrosophenol (10), which may be isolated, is oxidised very rapidly by nitric acid to yield the p-nitrophenol (11) and nitrous acid more nitrous acid is produced thereby and the process is progressively speeded up. No nitrous acid need be present initially in the nitric acid for a little of the latter attacks phenol oxidatively to yield HN02. The rate-determining step is again believed to be the formation of the intermediate (9). Some direct nitration of such reactive aromatic compounds by N02 also takes place simultaneously, the relative amount by the two routes depending on the conditions. 

We note that the difference between the enthalpy of formation of the unsubstituted benzoquinone/nitrosophenol and that of its isopropyl methyl cymene-like disubstituted derivative is 146 kJmol, comparable to that of the corresponding hydrocarbons, benzene and its substituted counterpart as liquids, 127.0 1.2 kJmol, and as the corresponding phenols as solids, 144.4 9.6 kJmol . ... 

If nitrosophenols are in equilibrium with quinone oximes, are nitrosoanilines in equilibrium with quinonimine oximes While in solution, 2-nitrosoanilines appear to show such behavior and crystallographic determination shows the benzenoid form is preferred . The enthalpy of formation of 4-nitrosodiphenylamine—or is it Af -phenyl-p-benzoquinone oxime—has been measured (213.1 3.2 kJmoD ), but as this value is for the solid we hesitate to make any thermochemical comparisons. Perhaps relatedly, the enthalpy of formation of 3,5-dimethyl-4-nitrosopyrazole has been determined but there are no data for any pyrazolones (1,2-diazacyclopentadienones as opposed to pyrazolinones) with which to make comparison with a putative oxime. 

An interesting reaction, the Baudisch reaction, involves the formation of nitrosophenols by the action of hydroxylamine hydrochloride and hydrogen peroxide, in the presence of metallic ions or certain Werner complexes, on aromatic compounds. The products are primarily o-nitrosophenol complexes of the metallic ion. Unfortunately, this reaction requires further development before it can be considered a reliable preparative procedure. 

In reactions of A,A-dimethylaniline, care must be taken in the final isolation of the free p-nitrosoamine from its salt, since prolonged treatment with excessive alkali leads to the formation of p-nitrosophenol [21a]. By the way, the initial proof that the product of nitrosation is the para isomer was simply based on the observation that, after prolonged add hydrolysis of p-nitrosophenol, a product formed which had an odor that resembled that of 1,4-benzoquinone. It is to be hoped that more substantial structure proofs are used today. 

In the course of treating lignin with nitric acid, especially with dilute acid, hydrocyanic acid is evolved. This is. explained by the formation of nitrosophenols that undergo a tautomeric conversion into quinone oximes, the latter then being oxidized and hydrolysed. During these reactions HCN is split off in a manner resembling that reported by Seyewetz [64] (compare Vol. I). 

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. 

The UV irradiation of phenol in the presence of nitrite (pH around neutrality) yields 4-nitrosophenol, catechol, hydroquinone, 1,4-benzoquinone, 2-nitrophenol and 4-nitrophenol [44,62,78,79]. It is interesting to observe that nitrophenols do not form in appreciable amount upon irradiation of 1.0 x 10-3 M phenol and nitrite, while relevant nitrophenol formation can be observed for [N02 ] > 1.0 x 10-3 M [44,79]. The formation of catechol, hydroquinone and 1,4-benzoquinone is most likely due to the photoinduced generation of hydroxyl (reactions 17 and 18). The relevant processes are initiated by hydroxyl attack on phenol (H-Ph-OH) in the presence of oxygen ([78,79] HO - Ph - OH catechol or hydroquinone, O = Ph = O 1,4-benzoquinone) ... 

An additional pathway for nitrophenol formation upon nitrite photolysis is linked with the nitrosation of phenol to yield 4-nitrosophenol, followed by the oxidation of 4-nitrosophenol to 4-nitrophenol [44]. A similar pathway involving phenol, 2-nitrosophenol and 2-nitrophenol might tentatively be postulated [65,66]. The nitroso derivative pathway is likely to be a secondary one in neutral to acidic solution [44,55], but it is a major source of 4-nitrophenol upon nitrite photolysis under basic conditions [59]. 

Finally, 4-nitrosophenol has also been detected as a transformation intermediate of phenol upon nitrate photolysis [54,58,79,99,100]. The occurrence of 4-nitrosophenol might be accounted for by the irradiation of photoformed nitrite and by the thermal reactions induced by nitrous acid. Indeed, the formation of 4-nitrosophenol upon nitrate irradiation is favoured at acidic pH [58] and 4-nitrosophenol forms in relevant amount in the presence of both nitrite under irradiation [44,59,110] and nitrous acid in the dark [55, 65-67]. 

Color Reaction Based on the Formation of Nitrosophenols (Pearl-Benson Method)... 

Of the methods for determining lignin in solution based on a specific chemical reaction, that involving nitrosation, the so-called Pearl-Benson method, has found the widest application. In this procedure, reaction of the phenolic units in lignin with acidified sodium nitrite leads to the formation of a nitrosophenol which, upon addition of alkali, is tautomerized to an intensely colored quinone mono-oxime. The absorbance of the latter structure is measured at 430 nm and related to lignin concentration by calibration with a standard lignin. The procedure described below is essentially that developed by Barnes et al. (1963), who modified the original Pearl-Benson method (Pearl and Benson 1940) to improve its sensitivity. 

It has also been demonstrated recently that the nitration of phenols in the presence of nitrous acid does not proceed by initial C-nitroso-compound formation (Ross et al., 1980). Product yields and orthoipara ratios were measured for the reaction of phenol with nitric acid alone, nitrous acid alone, and with both nitric and nitrous acid. The results for nitration could not be interpreted in terms of initial formation of 4-nitrosophenol but there was... 

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