Esters, of inorganic acids

The alcohol groups of unpleasant-tasting drugs are often converted to esters in order to mask the taste. In most cases, the ester has a less unpleasant taste than the free alcohol. 

The mechanisms of these reactions that form acid derivatives are covered with similar mechanisms in Chapter 21. 

Show the alcohol and the acid chloride you would use to make the following esters. 

In addition to forming esters with carboxylic acids, alcohols form inorganic esters with inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid. In each type of ester, the alkoxy (— OR) group of the alcohol replaces a hydroxyl group of the acid, with loss of water. We have already studied tosylate esters, composed of y flra-toluenesulfonic acid and alcohols (but made using tosyl chloride. Section 11-5). Tosylate esters are analogous to sulfate esters (Section 11-13A), which are composed of sulfuric acid and alcohols. 

A sulfate ester is like a sulfonate ester, except there is no alkyl group directly bonded to the sulfur atom. In an alkyl sulfate ester, alkoxy groups are bonded to sulfur through oxygen atoms. Using methanol as the alcohol. 

Strictly speaking the alkyl halides ate esters of the halogen acids, but since they enter into many reactions (e.., formation of Grignard reagents, reaction with potassium cyanide to yield nitriles, etc.) which cannot be brou t about by the oth esters, the alkyl halides are usually distinguished from the esters of the other inoiganic acids. The preparation of a number of these is described below. 

Alkyl sulphites. From the alcohol and thionyl chloride, for example 2C H, OH + SOCa, — (C4H, ) 03 + 2HC1 

Alkyl phosphates. From phosphorus oxychloride and the alcohol in the presence of pyridine, for example  

Alkyl borates. By heating boric acid with excess of the alcohol the water formed in the reaction is removed by fractional distillation as an azeotropic mixture with the alcohol, for example  

Alkyl thiocyanates. From potassium or sodium thiocyanate and the alkyl halide in alcoholic solution, for example  

Among the commercially important esters of inorganic acids are those of nitric, sulfuric, phosphoric, and silicic acids. The nitrates of glycerol and cellulose are among the oldest of synthetic chemical products. They are prepared by the direct esterification of the alcohol by nitric acW. 

In the nitration of cellulose, the reaction is carried out under accurately controlled conditions, so that a product having the desired properties is obtained. These properties differ according to the use for which the material is destined. The product, nitrocotton, is always clashed by the percentage of nitrogen that it contains. In carrying out the reaction, care must be taken to achieve uniformity of nitration, ance the valu of the product is largely dependent on its approach to homogeneity. 

A monosulfate is formed when sulfuric [reaction (25)] or chlorosulfonic acid [reaction (26)] reacts with an alcohol  

Reaction (25) is used for converting the higher alcohols into their monosulfates, which have wide use as detergents and wetting agents. 

The reactions of alcohols with nitric and sulfuric adds slow down and come to a standstill when the water formed in the reaction accumulates. The reactions are aided by an excess of sulfuric acid or sulfur trioxide. 

Cellulose is esterified with certain inorganic acids such as nitric acid, sulfuric acid, and phosphoric acid. A prerequisite is that the acids used can bring about a strong swelling thus penetrating throughout the cellulose structure. The esterification can be considered as a typical equilibrium reaction in which an alcohol and acid react to form ester and water. Of the inorganic esters cellulose nitrate is the only important commercial product. 

Cellulose nitrate is usually prepared in nitrating acid mixtures containing besides nitric acid sulfuric acid as a catalyst. The first reaction step involves generation of the nitronium ion (N02 )  

This reaction is an acid-base equilibrium in which sulfuric acid is the acid and the weaker nitric acid is the base, so that this kind of dissociation can take place instead of the formation of usual H and NO30 ions. In the next step the electrophilic nitronium ion attacks the hydroxyl groups of the cellulose  

Esterification is retarded by the formation of water which must be removed from the system to force the reaction to completion. 

The nitric acid concentration in the nitration acid mixture is usually 20-25%. The degree of nitration can be regulated by changes in the water content. Examples of the solubility and use of cellulose nitrates are given in Table 9-3. As a by-product in the nitration process some cellulose sulfate is also formed (see below). Because this results in instability of the cellulose nitrate, the sulfate groups must be removed by various treatments and the sulfuric acid formed removed by washing. 

Carboxylic acid anhydrides react similarly to acyl chlorides. 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed in detail in Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed. For the present, it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact. 

The acyl group of the carboxylic acid, acyl chloride, or acid anhydride is transferred to the oxygen of the alcohol. This fact is most clearly evident in the esterification of chiral alcohols, where, since none of the bonds to the stereogenic center is broken in 

Make a molecular model corresponding to the stereochemistry of the Fischer projection of 2-phenyl-2-butanol shown in the equation and verify that it has the R configuration. 

PROBLEM 15.9 A similar conclusion may be drawn by considering the reactions of the cis and trans isomers of 4-tert-butylcyclohexanol with acetic anhydride. On the basis of the information just presented, predict the product formed from each stereoisomer. 

---

Although the term ester used without a modifier is normally taken to mean an ester of a carboxylic acid alcohols can react with inorganic acids m a process similar to the Fis cher esterification The products are esters of inorganic acids For example alkyl nitrates are esters formed by the reaction of alcohols with nitric acid... 

Some esters of inorganic acids such as dimethyl sulfate are used as reagents m syn thetic organic chemistry Certain naturally occurring alkyl phosphates play an important role m biological processes... 

Formation of esters of inorganic acids (Section 15 9) Alkyl nitrates dialkyl sulfates trialkyl phos phites and trialkyl phosphates are examples of alkyl esters of inor game acids In some cases these compounds are prepared by the direct reaction of an alcohol and the inorganic acid... 

Esters. Esters of inorganic acids are named as the salts for example, ( 113)2804, dimethyl sulfate. However, if it is desired to specify the constitution of the compound, the nomenclature for coordination compounds should be used. 

For the properties of these compounds, see Esters, organic. For esters of inorganic acids, see the articles on nitric acid, phosphoric acids, sulfuric acid, etc. 

The most common impurities are the corresponding acid and hydroxy compound (i.e. alcohol or phenol), and water. A liquid ester from a carboxylic acid is washed with 2N sodium carbonate or sodium hydroxide to remove acid material, then shaken with calcium chloride to remove ethyl or methyl alcohols (if it is a methyl or ethyl ester). It is dried with potassium carbonate or magnesium sulfate, and distilled. Fractional distillation then removes residual traces of hydroxy compounds. This method does not apply to esters of inorganic acids (e.g. dimethyl sulfate) which are more readily hydrolysed in aqueous solution when heat is generated in the neutralisation of the excess acid. In such cases, several fractional distillations, preferably under vacuum, are usually sufficient. 

Esters of inorganic acids, including those given above and others, can be hydrolyzed to alcohols. The reactions are most successful when the ester is that of a strong acid, but it can be done for esters of weaker acids by the use of hydroxide ion (a more powerful nucleophile) or acidic conditions (which make the leaving group come off more easily). When vinylic substrates are hydrolyzed, the products are aldehydes or ketones. 

This chapter discusses pharmacologically and toxicologically relevant esters of inorganic acids, namely ... 

Hydrolysis of Alkyl Esters of Inorganic Acids Hydroxy-de-sulfonyloxy-substitution, etc. 

Hydrolysis of gem-dihalides 0-4 Hydrolysis of enol esters of inorganic acids... 

On the basis of experiments on the hydrolysis of numerous esters of inorganic acids carried out by Anbar et al. [53] this reaction has been defined by means of the three following equations ... 

Derivatives of nonmetals and alcohols with very low acidity (pK=15-19). These are esters of inorganic acids, characterized by low melting and boiling points, solubility in alcohols and nonpolar solvents, and sensitivity even to the traces of water. They are usually monomeric or weakly aggregated. The representatives of this group areB(OR)3, P(OR)3 and Se(OR)4. 

---