Alkyl nitrites hydrolysis

For a discussion of the mechanism of hydrolysis of alkyl nitrites, see Williams, D.L.H. Nitrosation Cambridge University Press Cambridge, 1988, p. 162. 

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) ... 

A novel mechanism of hydrolysis, and one of distinct pharmacological significance, has recently been uncovered in the biotransformation of glyceryl trinitrate [27], In a series of primary alkyl nitrites at pH 7.6 and 28°, f1/2... 

The acid hydrolysis of alkyl nitrites (Scheme 53) is inhibited by the presence of /I-cyclodextrin (CD) owing to the formation of 1 1 inclusion complexes that are unre-active or much less reactive than the RONO not complexed. The degree of inhibition... 

Alkyl methyl ketones undergo nitrosation at the reactive methylene group when treated with nitrous acid or an alkyl nitrite [Method (fi)]. The presence of hydrogen on the a-carbon permits tautomeric rearrangement to the oxime of a 1,2-dicarbonyl compound. Acidic hydrolysis of the oxime, which is best carried out in the presence of a hydroxylamine acceptor such as laevulinic acid,143 affords a further useful route to the 1,2-dicarbonyl system. 

The catalytic activity of artificial chymotrypsin in the hydrolysis of m-tert-butylphenyl acetate (k = 2.8xl02 s 1, KM = 13xl05M) was found to be close to the activity of chymotrypsin in the hydrolysis of p-nitrophenyl acetate (k,.at = l.lxlO2 s 1, KM = 4x105M). Another example of mimicking enzyme catalysis by P-cyclodextrin is general acid-base-catalyzed hydrolysis and nitrosation of amines by alkyl nitrites (Iglesias, 1998). 

Until relatively recently no kinetic studies on the nitrosation of alcohols had been reported, presumably since the reactions are very rapid and require special techniques. Some kinetic measurements on the reverse reaction, the hydrolysis of alkyl nitrites have been reported here conventional kinetic methods were used. Early workers examined the reactions of the series methyl, ethyl, i-propyl and t-butyl nitrites in an acetic acid-acetate buffer and found a small increase in rate constant along the series (Skrabal et a ., 1939). Later Allen measured the rate constants for the hydrolysis of a number of alkyl nitrites in aqueous dioxan solvent for both acid- and base-catalysed reactions (Allen, 1954). The rate constants for the O-nitrosation of alcohols were determined indirectly by measurement of the overall equilibrium constant for the process, by noting the change in the rate constant for the nitrosation of phenol in the presence of added alcohols. These, combined with the known data for the reverse hydrolysis reaction, enabled the rate constants for the forward reaction to be obtained (Schmid and Riedl, 1967). The reactivity sequence MeOH > EtOH > i-PrOH > t-BuOH was deduced, and attributed to a steric effect. 

Pyrlmidyl aldehydes and ketones are conveniently prepared by the reaction of methyl-substituted derivatives with alkyl nitrites the resulting aldoximes can be converted by hydrolysis to aldehydes, or by dehydration to nitriles, which can be further converted to ketones with Grignardj jea gents, or hydrolyzed and decarboxylated (replacement of -CH by -H). ... 

Several 1,3,5-triazine mono- and dialdoximes 5 can be prepared by the base-catalyzed condensation of the corresponding methyl-1,3,5-triazines 4 with alkyl nitrites. The formation of either the mono- or the dialdoxime is dependent on the reaction conditons used. Hydrolysis of the oximes to 1,3,5-triazinecarbaldehydes 6 can only be achieved for 4,6-diaryl-l, 3,5-triazine 2-al-doximes. These aldehydes can also be obtained by reaction of 4,6-diaryl-2-methyl-l,3,5-triazi-nes with sodium nitrite in concentrated sulfuric acid.162... 

The vast literature on applications of PTC in substitution reactions is mainly restricted to nucleophilic substitution reactions with an anionic reagent. However, recently the use of PTC in electrophilic reactions, like diazotization andazocou-pling C-and N-nitrosation, C-alkylation, acid hydrolysis of esters, chloromethylation, nitrite-initiated nitrations, and so on have been reported(Velichko et al., 1992 Kachurin et al., 1995). Alkylbenzene sulfonates and lipophilic sodium tetrakis[3,5-bis(trifluoromethyl)phenylboranate are typical electrophilic PT catalysts. Lipophilic dipolar molecules of the betaine type and zwitterionic compounds also function well as PT agents for both nucleophilic as well as electrophilic reactions. 

Alkyl nitrites in a liquid phase readily undergo hydrolysis, etherification, and other equilibrium reactions in terms of the following scheme yielding alcohols, alkyl nitrate, esters of organic acids, ethers and olefins [4] ... 

The effect of -cyclodextrin (jS-CD) on nitrosation and acid-base-catalysed hydrolysis of alkyl nitrites has been explored. ... 

There are a large range of lifetimes hsted in table IX-M-1. The most photochemically active class of molecules of those shown are the alkyl nitrites that have lifetimes of 4 min. (tert-C4H90N0) to 38 min. ( -C4H90N0) with an overhead Sun and diurnal photochemical lifetimes of 11 min. and 1.6 h during the June 22 period. The least-reactive photochemical species shown is CH3C(0)C1 that has a photochemical hfetime in the lower troposphere of hundreds of years during periods of low solar flux. Obviously, the losses of this species by other than photodecomposition, such as hydrolysis in cloud, rain, or ocean water, will be important. 

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. 

Also developed by Hill is a (diotochemical system (equations 41 to 48) based on a polyoxoacid, H3PWi2O40 (P)> The excited state of the acid probably oxidizes the alkane in the first step. The radical can then either attack the solvent to give an iminium radical, wiiich leads to ketone on hydrolysis, or it can be oxidized to the caifaonium ion, in wdiich case attack on the solvent leads instead to the -alkyl-acetamide. If the substrate has two adjacent tertiary C—bonds, then alkenes tend to be formed, llie Barton reaction, normally kmwn as an intramolecular C—activation, can give some intermolecular reaction in some examples. Thus, vdien n-octyl nitrite is rf)otolyzed in heptane, some nitrosoheptane is observed. ... 

---