Esters to Acid Anhydrides

On treatment with the appropriate nucleophile an acyl chlonde may be converted to an acid anhydride an ester an amide or a carboxylic acid Examples are presented m Table 20 1... 

Conversions of acid anhydrides to other carboxylic acid derivatives are illustrated m Table 20 2 Because a more highly stabilized carbonyl group must result m order for nucleophilic acyl substitution to be effective acid anhydrides are readily converted to carboxylic acids esters and amides but not to acyl chlorides... 

The carbonyl group of an amide is stabilized to a greater extent than that of an acyl chlo ride acid anhydride or ester amides are formed rapidly and m high yield from each of these carboxylic acid derivatives... 

These thermal methods for preparing amides are limited m their generality Most often amides are prepared m the laboratory from acyl chlorides acid anhydrides or esters and these are the methods that you should apply to solving synthetic problems... 

Amines are convert ed to amides on reaction with acyl chlorides Other acylating agents such as carboxylic acid anhydrides and esters may also be used but are less reactive... 

The primary and secondary alcohol functionahties have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Acyl transfer from an acid anhydride to an alcohol is a standard method for the preparation of esters. The reaction is subject to catalysis by either acids (H2SO4) or bases (pyridine). 

Conversion of Acid Anhydrides into Esters Acetic anhydride is often used to prepare acetate esters from alcohols. For example, aspirin (acetylsalicylic acid) is prepared commercially by the acetylation of o-hydroxybenzoic acid (salicylic acid) with acetic anhydride. 

When the -OH of a carboxylic acid is replaced by an -NH2, the compound produced is an amide. Amides are neutral to mildly basic compounds. They can be made from acids, acid chlorides, acid anhydrides, and esters by reaction with ammonia or primary and secondary amines. The amide linkage is found in polyamide resins such as nylon. 

Acid anhydrides are between acid chlorides and carboxylic acids in reactivity, so this reaction is more effective than the reaction with a carboxylic acid but less efficient than the reaction with an acid chloride. Half of the acid anhydride goes into forming the ester, while the other half becomes a carboxylic acid. Figure 12-23 illustrates this reaction, using salicylic acid as the alcohol and acetic anhydride as the acid anhydride to form aspirin, an ester. 

Water, alcohols, acids, anhydrides, and esters have varying chain-transfer properties [Mathie-son, 1963]. The presence of any of these transfer agents in sufficient concentrations results in Reaction 5-28 becoming the dominant mode of termination. Termination by these compounds involves transfer of HO, RO, or RCOO anion to the propagating carbocation. Aromatics, ethers, and alkyl halides are relatively weak chain-transfer agents. Transfer to aromatics occurs by alkylation of the aromatic ring. 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Monosaccharides contain a number of alcoholic hydroxyl groups, and thus can react with acid anhydrides to yield corresponding esters. For example, when glucose is treated with acetic anhydride and pyridine, it forms a pentaacetate. The ester functions in glucopyranose pentaacetate undergo the typical ester reactions. 

A ketone having an a-hydrogen atom may be acylated with an ester or an acid anhydride to form a p diketone ... 

The use of di- or poly-carboxylic acid anhydrides to cure epoxy resins is based on the reaction of these materials to produce ester links, in the presence of acidic or basic... 

The methyl group at position 5 in triazolopyrimidine 265 reacted with isoamyl nitrite to give the oxime 266, which was dehydrated to the car-bonitrile 267 (89EGP269149). Cyclization of the respective amidoxime 268 with acid chlorides, acid anhydrides, chloroformate esters and o-carboxylic acid esters gave the oxadiazolyl derivatives 269 (90EGP282009) (Scheme 51). 

Amides generally are formed from acid chlorides, acid azides, acid anhydrides, and esters. It is not practical to prepare them directly from an amine and a carboxylic acid without strong heating or unless the reaction is coupled to a second reaction that activates the acid (see Exercise 15-25). Notice that esters of phenols are more reactive toward amines than esters of alcohols because phenols are stronger acids than alcohols. 

Theoretically, this resonance could also take place in acid chlorides, acid anhydrides, and esters to give resonance structures (Fig.F). However, the process is much less important because oxygen and chlorine are less nucleophilic than nitrogen. In these structures, the positive charge ends up on an oxygen or a chlorine atom. 

Amides are the least of the acid derivatives and cannot be converted to acid chlorides, acid anhydrides, or esters. 

Carboxylic acids, acid chlorides, acid anhydrides and esters get reduced to primary alcohols when treated with lithium aluminium hydride (LiAlH) (Fig.M). The reaction involves nucleophilic substitution by a hydride ion to give an intermediate aldehyde. This cannot be isolated since the aldehyde immediately undergoes a nucleophilic addition reaction with another hydride ion (Fig.N). The detailed mechanism is as shown in fig.O. 

Azine approach. 4-Amino-5-hydroxypyrimidine condenses with acid anhydrides or esters to form the corresponding 2-substituted oxazolopyrimidine system (77CPB491). Under relatively mild reaction conditions the nucleoside 6-amino-5-hydroxyuridine will undergo cyclocondensation with formamide under the influence of polyphosphate ester to form the oxazolo-fused nucleoside (230) both protected and non-protected pyrimidine nucleosides have been used in this reaction (73CPB1327). 

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