Nitrite ester

The addition-elimination pathway can become very significant if the SN2 substitution and E2 elimination are largely suppressed, such as in the reaction of 18Ov with neo-C5HuONO. In that case the product ions N160180 and N1603 have been found to be formed in the ratio 20 1 

The reactions of the nitrites described have also been observed under FA conditions at much higher pressures. The increased pressure might explain the occurrence of an additional pathway observed in the reaction between enolate anions and nitrites and exemplified in (25b) (King et al., 1981). Path (b) has also been reported to occur in the reaction between the enolate anion of diisopropyl ketone and methyl nitrite in an ICR instrument operating at the relatively high pressure of 10 3 Pa (Klass and Bowie, 1980). 

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The hydroxyl groups on glycols undergo the usual alcohol chemistry giving a wide variety of possible derivatives. Hydroxyls can be converted to aldehydes, alkyl hahdes, amides, amines, a2ides, carboxyUc acids, ethers, mercaptans, nitrate esters, nitriles, nitrite esters, organic esters, peroxides, phosphate esters, and sulfate esters (6,7). 

The reactants are fed separately iato a stUl, from which the product is continuously removed by distillation (qv) (31). Isopropyl nitrate is a valuable engiae-starter fuel and can be used ia explosives (see Explosives and propellants) (32). The nitrite ester, isopropyl nitrite, can be prepared from the reaction of isopropyl alcohol and either nitrosyl chloride or nitrous acid at ambient temperature (33). The ester is used as a jet engine propellant (30). 

Several derivatives of cellulose, including cellulose acetate, can be prepared in solution in dimethylacetamide—lithium chloride (65). Reportedly, this combination does not react with the hydroxy groups, thus leaving them free for esterification or etherification reactions. In another homogeneous-solution method, cellulose is treated with dinitrogen tetroxide in DMF to form the soluble cellulose nitrite ester this is then ester-interchanged with acetic anhydride (66). With pyridine as the catalyst, this method yields cellulose acetate with DS < 2.0. 

A unique method for the degradation of 17-hydroxy-20-oxygenated pregnanes to 17-ketoandrostanes involves the photolysis of the corresponding nitrite esters.While this generally is equivalent to bismuthate or periodate oxidations, it is the only mild method for the conversion of a 17-hydroxy-... 

However, this does not explain the structural requirements for the oxygen function vicinal to the nitrite ester a-ketones, ketals and hydroxyls are cleaved, but a-acetoxyls are not. 

Table 3. Synthesis of ort/io-Substituted Fluoroaromatics from Nitrite Esters, Boron Trifluoride, and Hydrogen Fluoride [26]...

Cycloalkoxy radical intermediates are readily generated from a parent alcohol by various methods (e.g., nitrite ester photolysis, hypohalite thermolysis, lead tetraacetate oxidation) (83MI1). Once formed, reactive cycloalkoxy radicals undergo /3-scission to produce a carbonyl compound and a new carbon-centered radical. 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

The Barton reaction is usually carried out by irradiation of a nitrite ester 1 dissolved in a hydroxyl-free solvent under nitrogen atmosphere. Possible side-reactions can be decomposition reactions and intermolecular reactions sometimes the disproportionation may even predominate ... 

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

Scheme 19. Nitrite ester photolysis the Barton reaction.

By analogy with Levy s studies we might expect the formation and subsequent decompn of nitrite esters ... 

The solvent system N2O4/DMF has been employed for the preparation of inorganic esters, e.g., phosphates and sulfates [221] as well as organic esters. The latter products were obtained by reacting the polymer with acyl chlorides, or acid anhydrides in the presence of a pyridine base. The nitrite ester formed has been successfully trans-esterified by the reaction with RCOCl... 

The Nitrite Ion. This ion can give nitrite esters (R—O—N=0) (10-33) or nitro compounds (RNO2) (10-64), which are not esters. 

Sodium nitrite can be used to form nitro compounds with primary or secondary alkyl bromides or iodides, though the method is of limited scope. Silver nitrite gives nitro compounds only when RX is a primary bromide or iodide. Nitrite esters are an important side product in all these cases (10-33) and become the major product (by an SnI mechanism) when secondary or tertiary halides are treated with silver nitrite. 

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,... 

Figure 8, Photolytic generation of nitrogen dioxide and an aryl nitrite ester from a nitro compound, as formulated by Lippert and Kelm (27),...

Alkoxy radicals are also the active hydrogen-abstracting species in a procedure that involves photolysis of nitrite esters. This reaction was originally developed as a method for functionalization of methyl groups in steroids.379... 

The photolysis of nitrite esters has been found to be of considerable synthetic utility, particularly in functionalizing steroid methyl groups. The most spectacular application of this reaction has been a three-step synthesis of aldosterone.<59) Irradiation of corticosterone-11-nitrite (30) followed by nitric acid treatment gave aldosterone (32) in a 15% overall yield ... 

Radical migration of hydrogen is also known, though only over longer distances than 1,2-shifts, e.g. a 1,5-shift to oxygen via a 6-membered cyclic T.S. in the photolysis of the nitrite ester (129)—an example of the Barton reaction ... 

Mixtures of sodium nitrite and phthalic acid or phthalic anhydride explode violently on heating. A nitrite ester may have been produced. 

Tolerance to nitrates is defined as the reduction in hemodynamic effect or the requirement for higher doses to achieve a persistent effect with continuous use in the face of constant plasma concentrations [15]. Nitrate tolerance was first described for nitroglycerin in 1888 [36] it occurs with all organic nitrates, albeit to different extents. For reasons that are not understood, PETN appears to be the least susceptible to the development of tolerance. No, or much less, tolerance is observed with nitrite esters, such as amyl nitrite [37], molsidomine, and sodium nitroprusside. Earlier investigations suggested that a depletion of intracellular thiols is involved in tolerance development [17], but this has not been substantiated in later studies [38, 39]. As with organic nitrate bioactivation, the precise mechanism(s) involved in nitrate tolerance remain(s) unknown, but it is likely to be complex and multifactorial. Two principal... 

As noted under Mechanisms of Toxicity (Section 4.2), nitrate and nitrite esters are vasodilators with resulting hypotension (Nickerson 1975). Therapeutic doses of nitroglycerin for relief of angina are associated with headaches of vascular origin. Both PGDN and the structurally related ethylene glycol dinitrate produce headaches in humans and methemoglobinemia and hypotension in rats (Andersen and Mehl 1979). 

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