Carbonyl group substitution reactions

Carboxylic acids, esters, and amides have their carbonyl groups bonded to an atom (O or N) that strongly attracts electrons. All three families undergo carbonyl-group substitution reactions, in which a group we can represent as -Y substitutes for the -OH, -OC, or -N group of the carbonyl reactant. 

The most important reaction of esters is their conversion by a carbonyl-group substitution reaction into carboxylic acids. Both in the laboratory and in the body, esters undergo a reaction with water—a hydrolysis—that splits the ester molecule into a carboxylic acid and an alcohol. The net effect is a substitution of -OC by -OH. Although the reaction is slow in pure water, it is catalyzed by both acid and base. Base-catalyzed ester hydrolysis is often called saponification, from the Latin word sapo meaning "soap." Soap, in fact, is a mixture of sodium salts of long-chain carboxylic acids and is produced by hydrolysis with aqueous NaOH of the naturally occurring esters in animal fat. 

In contrast to the saturated azlactones, the Friedel-Crafts reaction of 2-substituted-4-arylidene-5-oxazolones is quite complex and may follow several different courses, often concurrently, depending on both reaction conditions and structural variations in the arylidene ring. This behavior is readily interpreted in terms of the a,)S-unsaturated carbonyl moiety and the cross-conjugated system containing nitrogen, both of which provide potential reaction sites in addition to the lactone carbonyl group. The reaction has been investigated " ... 

Chapters 1 and 2 dealt with formation of new carbon-carbon bonds by reactions in which one carbon acts as the nucleophile and another as the electrophile. In this chapter we turn our attention to noncarbon nucleophiles. Nucleophilic substitution is used in a variety of interconversions of functional groups. We discuss substitution at both sp3 carbon and carbonyl groups. Substitution at saturated carbon usually involves the Sjv2 mechanism, whereas substitution at carbonyl groups usually occurs by addition-elimination. 

In the reaction of rnr-3,6-dimethyl-l,4-dioxane-2,5-dione (m.-lactide) with sulfur tetrafluoride in hydrogen fluoride solution, together with fluorination of both carbonyl groups, substitution of one of the tertiary hydrogen atom by fluorine also occurs a diastcrcomeric mixture of 2,3,3.6,6-pcntafluoro-2,5-dimethyl-l,4-dioxane (12) is formed in 75% yield (cf. Section 8.2.7.).166... 

Nucleophilic attack on the carbon atom of the carbonyl group, in reactions which lead to substitution rather than to ring opening, is discussed in this section. 

One of the most important chemical transformations of carboxylic acids is their acid-catalyzed reaction with an alcohol to yield an ester. Acetic acid, for example, reacts with ethanol in the presence of H2SO4 to yield ethyl acetate, a widely used solvent. The reaction is a typical carbonyl-group substitution, with -OCH2CH3 from the alcohol replacing -OH from the acid. 

The lone pairs may act as nucleophiles in substitution reactions of alkyl halides and sulfonates, in the solvolysis of epoxides, and in addition reactions to carbonyl groups. These reactions often proceed with acid or base catalysis. 

Reactions can also occur at the a carbon to the carbonyl group. These reactions proceed by way of ends or enolates, two electron-rich intermediates that react with electrophiles, forming a new bond on the a carbon. This reaction results in the substitution of the electrophile E for hydrogen. 

Another common method for cleavage of substituents a to a carbonyl group involves reaction of the substituted carbonyl compound with an appropriate nucleophile. Such reactions are believed to occur by nucleophilic attack upon the a-substituent to afford an enolate (equation 2). Nucleophiles which can accomplish this conversion encompass a wide variety of structural types. Some of the best methods for reduction of halocarbonyl compounds fall into this category. 

The large group of phenol-formaldehyde, urea-formaldehyde, and melamine-formaldehyde polymers are also prepared by carbonyl-addition-substitution reactions. Their final crosslinking reaction occurs in the solid state, however, the polymers are amorphous. Crystalline linear polymers have been obtained using parasubstituted phenols. But up to now only relatively low molecular weight polymers have been prepared (5). 

Like other acid derivatives, acid chlorides typically undergo nucleophilic substitution. Chlorine is expelled as chloride ion or hydrogen chloride, and its place is taken by some other basic group. Because of the carbonyl group these reactions take place much more rapidly than the corresponding nucleophilic substitution reactions of the alkyl halides. Acid chlorides are the most reactive of the derivatives of carboxylic acids. 

Substitution at carbonyl groups chIO reactions compounds as nucleophiles ch21... 

Carbonyl addition-substitution reactions the reaction of aldehydes with alcohols involving addition followed by substitution at the carbonyl group leading to the formation of polyacetals ... 

---