Hydrolysis of Nitrate Esters

Monohydiic alcohol and polyhydric alcohol nitrate would be hydrolyzed in weak alkaline or weak acidic agents, but they are relatively difficult to be hydrolyzed in neutral agents. The hydrolysis process is shown in the following equation. 

Besides the main products of alcohols and acids, other compounds, including aldehyde, ketone, hydroxycarboxyUc acid, unsaturated hydrocarbons, and nitrous acid, can be obtained in the hydrolysis process of nitrate esters [31]. 

C3H4(0N02)2+5K0H KNO2 + 2KNO3 + CH3COOK + HCOOK + 3H2O 

This equation cannot stand for all hydrolysis process of esters [32, 33]. In the same conditions, the hydrolysis products of dUferent nitrate esters include phenolic resin, oxalic acid, and ammonium. In alkaline agents, glycCTol is not found in the 

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Baker and co-workers (Vol. 11, p. 8. 123-25 ) have undertaken extensive research on alkaline hydrolysis of nitrate esters. Their results, as those of ilie othci authors (271. were reviewed [2, 3. Tlicy can be summari/cd as follows... 

An interesting method of hydrolysis of nitrate esters to alcohols was given by Pews 1158). It consists in refluxing nitrate esters with formic acid followed by refluxing with methanol. Pemaerythritol trinitrate yielded pentaerythritol. 

Nitrous acid is only produced in the hydrolysis of nitrate esters with peroxide structure. Under the influence of hydrolytic reagent, the structure of nitrate esters would be changed to peroxide structure. Thus, nitrous acid would be produced in the process. 

Compared with nitrous acid ions, nitric acid ions can be slowly reduced in sodium sulfhydrate. The nitrous acid ions are produced from the hydrolysis of nitrate esters, other than from the reduction of nitric acid ions. Thus, the nitrous acid ions are formed, most likely, by the breakage of bonds between oxygen and nitrogen atoms. The effect of sulfhydrate on the hydrolysis of nitrate esters is to reduce the reactants, as expressed in the following reaction mechanism equations. 

There are many methods to reduce nitrate esters from ester groups to alcoholic hydroxyl groups, most likely to obtain the corresponding alcohols. The oldest, also the most common, reduction method is the reductive hydrolysis by alkali sulfide or alkali sulfhydrate, such as sodium sulfide, ammonium sulfide, or corresponding sulfhydrate [39]. Transesterification reaction would happen in the hydrolysis of nitrate esters by sulfuric acid to form sulfate esters [40]. 

Nitrophenylacetic acid has been formed by the nitration of phenylacetic acid 1 by the hydrolysis of its ester 2 or its amid 3 and by the hydrolysis of its nitrile with hydrochloric acid.4... 

Alkahne hydrolysis, followed hy the use of sulfanihc acid and 1-naphtylamine, was the basis of a spot test for NG [37], as well as for several nitrate esters and nitramines, including NG, NC, tetryl, and RDX [38]. It is also a common spray for the detection of nitrate esters and nitramines on TLC plates [25, 29, 37, 39—41]. 

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. 

In experiments with benzyl nitrate the same workers have established that during the hydrolysis of this ester a certain quantity of benzaldehyde is obtained together with benzyl alcohol ... 

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. 

Since in numerous cases of hydrolysis of nitric esters the presence of a large amount of nitrate ion has been established, which could be liberated only by rupture of the C—0 bond, the factors that influence the direction of this process should be discussed. Several investigations have thrown light on this problem, which is more complicated than with carboxylic esters, since during the hydrolysis of the latter compounds whether in acid or in alkaline medium only rupture of the ester bond can take place. This has been established in various ways including the use of water containing an 180-isotope. In general the hydrolysis of carboxylic esters can be defined by the equation ... 

Cerium(IV) ammonium nitrate (CAN) is effective for oxidative hydrolysis of phenyl esters substituted by hydroxyl, methoxyl, and dimethylamino groups in CH3CN-H20 at 0°. 

Cordes and co-workers 191 found that the alkaline hydrolysis of p-nitrophenyl hexanoate is subject to catalysis by polyvinylpyridine-based polysoaps. For example, k bs is increased from 0.1 mm to 1.4 mm in the presence of 5 x 10 7 M 38% polysoap (23) (the same material used in the Strauss work). With 5 x 10-7 M polymer having a 15 % dodecyl content, the rate is increased only 3 times above background. The simplest rationale for the kinetics invokes both hydrophobic and electrostatic forces. Thus, dodecyl chains on the polymer hydrophobically bind p-nitrophenyl hexanoate to the polymer surface. Since the polymer possesses a high density of cationic nitrogens, hydroxide ions also accumulate at the polymer surface where they catalyze the hydrolysis of bound ester. Addition of nitrate ion to the aqueous reaction... 

The stable pyrazole acid from the hydrolysis of this ester is a key intermediate in Viagra production. Nitration can occur only at the one remaining free position and then amide formation and reduction complete the synthesis of the amino pyrazole amide ready for assembly into Viagra. 

The four modes of hydrolysis can explain the reaction of nitrate esters with other nucleophiles such as ammonia and amines, hydra7tnc (Vol. II, p. 12). hydroxide and alkoxide ions (.S l and S 2). Here the esters can act as alkylating agents. 

This particular problem was studied by Camera. Zotti and Modena [3, 4]. They identified some of the products of the action of nitrating acid on ethyl nitrate as a mode for the behaviour of nitrate esters in acid solution. They came to the conclusion that the initial process consisted in hydrolysis of the ester. The hydrolytic equilibrium was disturbed by oxidation of the alcohol by liberated nitric add. In the instance of ethyl nitrate the freed ethanol was oxidized to acetaldehyde. Some other products were also formed. Nitric acid was reduced to... 

I rasei [67] examined the stability of nitrate esters by determining the hydrolysis rates of the esters using sodiutii hydroxide in 909f ethanol at 30 and 60 (. The reactions are all second order in both nitrate ester and hydroxide ions. As the measure of the stability of an ester Fraser took the initial specific rate of hydrolysis. His results arc summarized in Tabic 48. 

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