Acyl group derivatives Carboxylic acids Ketones

There are non-systematic number roots for hydrocarbon derivatives containing acyl groups or derived from acyl groups. These are the ketones, carboxylic acids, esters, nitriles, and amides ... 

Ketones, aldehydes, and carboxylic acids all contain the carbonyl group, yet the reactions of acids are quite different from those of ketones and aldehydes. Ketones and aldehydes commonly react by nucleophilic addition to the carbonyl group but carboxylic acids (and their derivatives) more commonly react by nucleophilic acyl substitution, where one nucleophile replaces another on the acyl (C=0) carbon atom. 

The first stage of the mechanism for nucleophilic acyl substitution is exactly the same as for nucleophilic addition to the carbonyl group of an aldehyde or ketone. Many of the same nucleophiles that add to aldehydes and ketones—water (Section 17.6), alcohols (Section 17.8), amines (Sections 17.10-17.11)—add to the carbonyl groups of carboxylic acid derivatives. 

You learned in Chapter 17 that nucleophilic addition to aldehydes and ketones is one of the fundamental reaction types of organic chemistry, then in Chapter 19 you saw that addition to carbonyl groups in carboxylic acid derivatives can lead to nucleophilic acyl substitution. In this chapter, you ll encounter a third pattern of carbonyl reactivity—one that involves the enol tautomers of aldehydes, ketones, and esters and the conjugate bases of enols known as enolates. 

Notice that the acyl groups of carboxyhc acids and carboxylic acid derivatives are attached to weaker bases than are the acyl groups of aldehydes and ketones. (Remember that the lower the the stronger the acid and the weaker its conjugate base.) The hydrogen of an aldehyde and the alkyl group of a ketone are too basic to be replaced by another group. 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

The second fundamental reaction of carbonyl compounds, nucleophilic acyl substitution, is related to the nucleophilic addition reaction just discussed but occurs only with carboxylic acid derivatives rather than with aldehydes and ketones. When the carbonyl group of a carboxylic acid derivative reacts with a nucleophile, addition occurs in the usual way, but the initially formed tetra-... 

As a general rule, nucleophilic addition reactions are characteristic only of aldehydes and ketones, not of carboxylic acid derivatives. The reason for the difference is structural. As discussed previously in A Preview of Carbonyl Compounds and shown in Figure 19.14, the tetrahedral intermediate produced by addition of a nucleophile to a carboxylic acid derivative can eliminate a leaving group, leading to a net nucleophilic acyl substitution reaction. The tetrahedral intermediate... 

The difference in behavior between aldehydes/ketones and carboxylic acic derivatives is a consequence of structure. Carboxylic acid derivatives have ai acyl carbon bonded to a group -Y that can leave as a stable anion. As soon a the tetrahedral intermediate is formed, the leaving group is expelled to general- a new carbonyl compound. Aldehydes and ketones have no such leaving grouj however, and therefore don t undergo substitution. 

Compounds containing geminal carboxyl groups (disubstituted malonic acid derivatives) can also be bisdecarboxylated with lead tetraacetate, gcm-diacetates (acylals) being produced, which are easily hydrolyzable to ketones ... 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Figure 6.50 displays acylations of C nucleophiles with NMe(OMe) derivatives of carbonic instead of carboxylic acids. The discussion of acylation reactions with NMe(OMe) derivatives of carboxylic acids ( Weinreb amides ) in Figures 6.42 and 6.44 revealed that the NMe(OMe) group has two effects first, it increases the reactivity and second, it is responsible for the occurrence of clean acylations. Against this background we will leave you to your own studies of a picture without words, namely Figure 6.50. Convince yourself that the approaches A —4 C, D —> C and E —> C to Weinreb amides outlined in this figure work and find out why alternative ketone syntheses D —> H and E —> H are also possible ...

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