Formation of nitric esters

The simplest and most commonly used method of preparing nitric esters consists in the O-nitration reaction of alcohols with nitric acid, usually in the presence of sulphuric acid. The reaction is accompanied by reversible hydrolysis, which is typical of esterification reactions. It is very likely that the main nitrating agent is the nitronium ion NO (nitryl cation). It acts through electrophilic substitution. The presence of sulphuric and perchloric acids in the esterifying mixed acid favours the esterification, as it increases the concentration of NO ion. 

When investigating the O-nitration of glycerol Ingold et al. [68] established that primary alcoholic groups are attacked with NO very quickly and the reaction is of zero order. The secondary alcoholic group reacts at a lower rate and the reaction is of the first order. 

It was observed that the presence of sulphuric acid promotes the hydrolysis of esters (e.g. [104,107,109]). The rate of hydrolysis is for the most part significantly lower than the esterification rate. Moreover, as already discussed above, in addition to the main reaction producing alcohol and nitrating acid, the hydrolysis process is generally accompanied by side reactions. Acids other than sulphuric, or perchloric [104], e.g. acetic [106] or phosphoric, if present in the esterifying mixture, hydrolyse esters to a markedly smaller extent than sulphuric acid. The acid make up of an esterification mixture in industry is established experimentally. Economic factors also plays a part here. 

In addition to these chemical reactions outlined above oxidation reactions also take place during the esterification process. 

Kaverzneva, Ivanov and Salov [69] found that isopropyl alcohol, under the influence of dinitrogen tetroxide at normal temperature, is transformed into acetone. Ethylene glycol is oxidized rapidly by it to oxalic and glycolic acids. 

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The sensitiveness and number of chemical changes is greatly augmented by the presence of an alkyl radical in the para position, facilitating, probably, the formation of nitric esters. (R-NO(OH)2). 

Klason and Carlson were of the opinion that the formation of nitrous acid takes place owing to the peroxy structure of nitric esters, as these, under the influence of a hydrolysing agent, would change their structure and be transformed into peroxy compounds. Simultaneously nitrous acid would be formed ... 

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) ... 

It is necessary to take into consideration the fact that the decomposition of nitric esters has an autocatalytic character water and nitrogen dioxide formed during the decomposition lead to the formation of nitric and nitrous acids which accelerate the reaction of decomposition of the nitric ester. The influence of nitric acid on the rate of decomposition of nitroglycerine was studied by Roginskii [79] and is described below. 

Under conditions simultaneously favorable for these equilibria and unfavorable for carbon-carbon bond cleavage, the specificity of the reaction is greatly increased. Oxidation of primary alcohol groups appears to proceed through the intermediate formation of an ester of nitric (or nitrous) acid. 

O-nitration, leading to the formation of nitric acid esters, with the nitro group attached to an oxygen atom ... 

Systematic studies have been made of nitrations in both nitric-phosphoric and nitric-sulphuric mixes, both from a surface and bulk point of view. For nitric phosphoric mixes the DOS depends on the composition and there is little evidence for formation of phosphate esters. The DOS in the surface region therefore represents the equilibrium between nitration and de-... 

As might be anticipated from the dependency of CBF on intracellular cAMP, -agonists elevate CBF, although the concentrations required to do this are greater than those required for bronchodilatation (Pavia etal., 1984). Evidence from primary cultures of bovine bronchial epithelium has been presented which su ests that a component of the isoprenaline-stimulated increase in CBF is dependent up)on the formation of nitric oxide (NO Jain eteU., 1993). The nitric oxide synthase (NOS) inhibitors L-nitromonomethyl arginine (L-NMMA) and L-nitroarginine methyl ester (L-NAME) both reduced... 

The acidity of the mixed acids, not their dehydrating power, has been established as being the rate criterion for the formation of true nitro compounds that it might be extended to the case of nitric esters seems a reasonable assumption. ... 

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. 

It is not only the esters of organic acids which combine, in the manner of the ethyl acetoacetate synthesis , with the enolates of ketones and of esters an analogous behaviour is shown by the esters of nitrous and nitric, acids. The process which leads to the formation of isonitroso-and atinitro-compounds yields products fundamentally similar to those already described just as with ethyl acetate the group CO.CHs enters, so here, the NO- and N02-groups are involved, and enolise " exactly as does >O=0 ... 

Nichols and co-workersstudied the formation of j8-hydroxy nitrate esters via the acid-catalyzed ring-opening of epoxides with nitrate anion. Reactions were conducted in aqueous media using solutions of ammonium nitrate is nitric acid and under nonaqueous conditions using solutions of pure nitric acid in chloroform. 2-Nitratoethanol (32) is formed in 58 % yield from ethylene oxide (30) using either of these methods. ... 

Treatment of DPT (239) with dinitrogen pentoxide in pure nitric acid leads to the isolation of the nitrate ester (249), an unstable explosive which is highly sensitive to impact and readily undergoes hydrolysis. A low nitration temperature favours the formation of (249) and its presence during the nitrolysis of hexamine is clearly undesirable. The nitrolysis of DPT (239) with one equivalent of pure nitric acid in an excess of acetic anhydride yields 1-acetomethyl-3,5,7-trinitro-l,3,5,7-tetraazacyclooctane (251), a useful starting material for the synthesis of other explosives. ... 

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