Hydrolysis of nitric esters

Nitric esters of monovalent and polyvalent alcohols are hydrolysed by comparatively mild reagents in alkaline or add media and with slightly more difficulty in a neutral medium. Theoretically, this process might be expressed by the following equation  

However, the alcohol and acid formed during the hydrolysis of nitric esters are accompanied by a range of other compounds such as aldehydes, ketones, hydroxy-carboxylic acids, unsaturated hydrocarbons, nitrous add, etc. (e.g. reference [107]). 

In certain cases the hydrolysis process does not result in the formation of the initial alcohol at all, but a series of other compounds is obtained, by a reaction mechanism which is often unknown. As an example, the hydrolytic reaction of nitroglycerine performed in an aqueous or alcoholic solution of sodium or potassium hydroxide can be quoted. Oxidation and reduction processes take place simultaneously to form organic acids as well as nitrates and nitrites. After Hay [32] the course of the reaction can be summarized by the eqn. (2)  

C3H5(0N02)3 + 5KOH ---- KN03 + 2KN02 + CH3COOK + HCOOK + 3 H20 (2) 

This equation does not present a full picture of the chemical changes that occur, before Vignon and Bay [33], Silberrad and Fanner [34] and Berl and Delpy [35] identified the presence of aldehyde resins, oxalic acid and ammonia among the products of hydrolysis performed under similar conditions. 

CjHjIONOjls -1- 5KOH -- KNO3 + 2KNO2 + CHjCOOK -I- HCOOK + 3H2O (2) 

---

However, Matsushima [lb] suggested that peroxides may be formed in the course of hydrolysis of nitric esters (4) as transition products prior to the formation of aldehydes (5) ... 

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. 

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 ... 

Physical properties Dipole moments Spectroscopy Hydrolysis of nitric esters Reduction of nitric esters Some 4>thcr reactions of nunc esters Form Jlion of nitric esters Nitric esters as explosives C hemical stability... 

E. Schulek et al, Hydrolysis of Nitric Acid Esters (Nitro Compounds) ,... 

Belkner et al. [32] demonstrated that 15-LOX oxidized preferably LDL cholesterol esters. Even in the presence of free linoleic acid, cholesteryl linoleate continued to be a major LOX substrate. It was also found that the depletion of LDL from a-tocopherol has not prevented the LDL oxidation. This is of a special interest in connection with the role of a-tocopherol in LDL oxidation. As the majority of cholesteryl esters is normally buried in the core of a lipoprotein particle and cannot be directly oxidized by LOX, it has been suggested that LDL oxidation might be initiated by a-tocopheryl radical formed during the oxidation of a-tocopherol [33,34]. Correspondingly, it was concluded that the oxidation of LDL by soybean and recombinant human 15-LOXs may occur by two pathways (a) LDL-free fatty acids are oxidized enzymatically with the formation of a-tocopheryl radical, and (b) the a-tocopheryl-mediated oxidation of cholesteryl esters occurs via a nonenzymatic way. Pro and con proofs related to the prooxidant role of a-tocopherol were considered in Chapter 25 in connection with the study of nonenzymatic lipid oxidation and in Chapter 29 dedicated to antioxidants. It should be stressed that comparison of the possible effects of a-tocopherol and nitric oxide on LDL oxidation does not support importance of a-tocopherol prooxidant activity. It should be mentioned that the above data describing the activity of cholesteryl esters in LDL oxidation are in contradiction with some earlier results. Thus in 1988, Sparrow et al. [35] suggested that the 15-LOX-catalyzed oxidation of LDL is accelerated in the presence of phospholipase A2, i.e., the hydrolysis of cholesterol esters is an important step in LDL oxidation. 

Much experimental work has been carried out in seeking an explanation of the mechanism of the hydrolysis process of nitric esters but a relatively satisfactory theoretical explanation of the phenomenon has been found only recently. 

In the investigation with n-butyl nitrate by Merrow, van Dolah and Cristol [41] already cited, neither the presence of the nitrate ion nor of mercaptan was detected. For this reason the following reaction mechanism was proposed for the hydrolysis of nitric acid alcohol esters by means of hydrosulphide ... 

When acting with dinitrogen tetroxide on ethylene oxide and homologues followed by hydrolysis a nitric ester of the type (IV) is formed (Pujo etal. [108], Rossmy [75]). 

To make rosoxacin two heterocyclic systems must be constructed. Workers at the pharmaceutical company Sterling decided to build the pyridine in an ingenious version of the Hantzsch synthesis using acetylenic esters on 3-nitrobenzaldehyde. The ammonia was added as ammonium acetate. Oxidation with nitric acid made the pyridine, hydrolysis of the esters and decarboxylation removed the acid groups, and reduction with Fe(TT) and HC1 converted the nitro group into the amino group required for the quinolone synthesis. 

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... 

According to Kohler and Marquc>Tol calcium carbonate does not affect the test directly, but in presence of water it gives rise to hydrolysis of nitrocellulose and forms traces of calcium nitrite, which lower the test. If, however, the conditions be closely adhered to, it Serves a useful purpose, especially in the manufacture of nitric esters. It is also very simple to apply ... 

Hydrolysis of t-esters. t-Butyl and adamantyl carboxylates are cleaved by nitric acid (9 examples, 92-99%). ... 

Normally, one does not think of carbons as catalysts. However, carbons are sufficiently acidic or can be treated with nitric acid to be made acidic. These acidic carbons catalyze the hydrolysis of methyl esters. The carbons are more thermally robust than acidic sulfonic ion-exchange resins and can routinely operate at temperatures greater than 100°C. The nature of the acidic groups on... 

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. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

Bromobenzaldehyde has been prepared by the oxidation of -bromotoluene with chromyl chloride/ by saponification of the acetal from />-bromophenylmagnesium bromide and orthoformic ester/ by the oxidation of ethyl -bromobenzyl ether with nitric acid/ by the oxidation of /j-bromobenzyl bromide with lead nitrate/ and by the hydrolysis of i-bromobenzal bromide in the presence of calcium carbonate. ... 

---