Nitrite esters, hydrolysis

Another related reaction is the Barton reaction, by which a methyl group in the 0 position to an OH group can be oxidized to a CHO group. The alcohol is first converted to the nitrite ester. Photolysis of the nitrite results in conversion of the nitrite group to the OH group and nitrosation of the methyl group. Hydrolysis of the oxime tautomer gives the aldehyde, for example,... 

C-H bond unreactive to insertion, 1160 hydrolysis, 701-2 Nitrite, TEARS assay, 667 Nitrite esters, hydroperoxide determination, 684... 

The reaction of lb with sodium nitrite in dimethylformamide, in the presence of urea and 1,3,5-trihydroxybenzene (phloroglucinol), gives 1 //,l//,2//,2//-unicosafluoro-l-nitro-dodecane (2b) in 51 % yield.7 The side product, 1 //,l//,2//,2//-unicosafluorododecan-l-ol (3b), resulting from hydrolysis of the corresponding nitrite ester, is isolated in 40% yield.7... 

Nitrate ester hydrolysis is not catalysed by mineral acids lo an appreciable extent [29, 26), This is in contrast to nitrite esters which readily hydrolyse in lan acid medium. According to Dewai [30] nitrate esters are proionated prefer-[cntially at the alkoxy oxygen according to equation (5a) ... 

Products formed include the cis- and trans-isovaers of 2-trinitromethyl-3-nitro-2,3-dihydrobenzofuran, 2-trinitromethyl-3-hydroxy-2,3-dihydrobenzofuran (from hydrolysis of the nitrite ester), 2-nitro-3-trinitromethyl-2,3-dihydrobenzo-furan, 4-trinitromethyl-7-nitro-4,7-dihydrobenzofuran and nitronic ester (274). ... 

In runs in acetic acid, the oxygen atom of the alcohol probably originates in the nitrite ion through species 49 and paths (d) and (g) (equation 146). Under certain conditions, a portion may also arise through path (e) involving the formation of a nitrite ester followed by hydrolysis this path, however, does not account for the alcohol-ester ratios given by the series of amines mentioned in the last part of section (1). Dilution of the acetic acid solvent by water (up to 8 mole % of water) had no effect on the stereochemical results in the deamination of 2-phenyl-2-butylamine % and dilution up to 50 mole % water had only a small effect in other deaminations... 

The esters of nitrous acid are characterised by their high velocities of formation and hydrolysis. They are almost instantaneously decomposed by mineral acids and in the method of preparation given this has been taken into account. The slightest excess of hydrochloric acid must be avoided. Advantage is taken of this property of the alkyl nitrites in all cases where it is desired to liberate nitrous acid in organic solvents (in which metallic nitrites are insoluble). Examples addition of N203 to olefines, preparation of solid diazonium salts (p. 286), production of isonitroso-derivatives from ketones by the action of HN02. This synthesis is often also carried out in the manner of the acetoacetic ester synthesis, with ketone, alkyl nitrite, and sodium ethylate the sodium salt of the isonitrosoketone is formed (cf. in this connexion p. 259) ... 

Hydrazine salts have been prepared by the action of hypochlorites on ammonia1 or urea 2 by the hydrolysis of salts of sulfohydrazimethylene disulfonic acid 3 by the hydrolysis of triazoacetic acid 4 by the reduction of diazoacetic ester 5 by the reduction of nitroguanidine followed by hydrolysis 6 by the reduction of the nitroso derivatives of hexamethylene tetramine 7 by the reduction of nitrates or nitrites with zinc in neutral solution 8 by the action of sodium bisulfite on hyponitrous acid... 

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

According to Fanner [38] the first stage of hydrolysis proceeds in accordance with the eqn. (1) (p. 7). Afterwards, the products react with one another to form nitrous acid or nitrites and the series of compounds ennumerated above. Fanner s hypothesis seems unsatisfactory when hydrolysis of nitric esters is carried out in a neutral medium since, for example, if ethyl alcohol is treated with an aqueous solution of potassium nitrate no oxidation of the ethyl alcohol occurs even if the mixture of compounds is boiled. 

Reductive hydrolysis of n-butyl nitrate in an aqueous solution of ethyl alcohol in the presence of sodium hydrosulphide or ammonium hydrosulphide has been carried out by Merrow, Cristol and van Dolah [41], This is a complicated chemical reaction. As the result of hydrolysing the nitrate in the presence of sodium hydro-sulphide (the alkalinity of the solution corresponds to pH 10-11) 93% of nitrite ions and 7% of ammonia are obtained from the ester group nitrogen. When ammonium hydrosulphide is used, the nitrite ions initially produced rise to a maximum concentration and then fall to zero owing to the reducing action of the ammonium hydrosulphide. The reduction process takes place more effectively when the pH is above 10. 

The above mentioned authors also established that the nitrate ion (in contrast with the nitrite ion) slowly undergoes reduction in the presence of sodium hydrosulphide. This leads to the conclusion that the nitrite ion formed during the hydrolysis of nitric esters cannot be produced by the reduction of a nitrate ion. Hence if the nitrite ion is formed direct during the hydrolysis of nitric esters, then it could only be produced by breaking the linkage between the oxygen and nitrogen atoms. 

A new heterocyclic ring system, 5//-pyrazolo[3,4- /]-l, 2,3-thiadiazoles (41), results from a one-pot, two-step reaction of the pyrazolodithiazolium chlorides (29). Sequential treatment of the derivatives (29) with base, sodium dithionite, and sodium nitrite followed by acidification afforded (41) (Scheme 3). For substrates (29a,b) potassium hydroxide was chosen, whilst for (29c,d) sodium bicarbonate was found to be superior. In the latter cases, potassium hydroxide caused appreciable hydrolysis of the ester substituent. A further point of interest is the significant quantity of disulfide (43) which can form on reaction of 6-carboethoxy-5-methylpyrazolodithiazolium chloride (29c). This, however, need not represent a problem since compound (43) can be converted in situ or isolated and converted to the desired product (41c) in good yield (Scheme 4) <84JOCl224>. 

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