Nucleophilic reactions of carbonyl groups

Nucleophilic reagents attack the carbonyl carbon atom the subsequent course of this reaction parallels that in aliphatic chemistry. If the carbonyl group and the heteroatom are adjacent, the ring is usually opened. If they are not adjacent, a carbonyl addition compound results, which often eliminates water spontaneously. The reactions of carbonyl groups in both environments are discussed. 

Many reactions of carbonyl groups are acid-catalyzed. The acid attacks the electronegative oxygen, which bears a partial negative charge, to create a carbocation that subsequently reacts with the nucleophile ... 

While this approach has been applied primarily to nucleophilic reactions of carbonyl compounds, it can also be used to determine the primary direction of hydrogenation since adsorption on a catalyst surface is preferred from the less hindered side of the carbonyl group. The synthesis of dl ephedrine (20) was accomplished by the hydrogenation of the amino ketone, 19, one enantiomer of which is depicted in Eqn. 14.17.5 xhe hydrogen bond to the carbonyl oxygen helps fix the conformation with hydrogenation taking place from the side of the... 

Most reactions of carbonyl groups occur by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, am carbonyl condensation. These mechanisms have many variations, just a alkene electrophilic addition reactions and 8 2 reactions do, but the varia tions are much easier to learn when the fundamental features of the mechanisms are understood. Let s see what the four mechanisms are and what kinds of chemistry carbonyl groups undergo. 

The mechanistic picture established by study of hydration and alcohol addition reactions sets a pattern that will be evident in a number of other carbonyl reactions. The initial step is usually nucleophilic addition to the carbonyl group. This can be acid-catalyzed or base-catalyzed. Other reactions of carbonyl groups branch out mechanistically from this common nucleophilic addition step, and differ primarily in the fate of the addition intermediate. 

Carboxylic acids are electrophiles (Lewis acids) as well as Bronsted acids. The presence of the carbonyl group ensures that. Remember all the addition reactions of carbonyl groups encountered in Chapter 16. However, expression of the Lewis acidity of the carbonyl carbon is often thwarted because the easiest reaction with a nucleophile is not addition to the carbonyl group, but removal of the acid s OH hydrogen to give the carboxylate anion. Once it is formed, the carboxylate anion is far more resistant to addition than an ordinary carbonyl because, in this case, addition would introduce a second negative charge (Fig. 17.11). 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds its central theme is a fundamental reaction type nucleophilic addition to carbonyl groups The principles of nucleophilic addition to aide hydes and ketones developed here will be seen to have broad applicability m later chap ters when transformations of various derivatives of carboxylic acids are discussed... 

In many reactions at carbonyl groups, a key step is addition of a nucleophile, generating a tetracoordinate carbon atom. The overall course of the reaction is then determined ly the fate of this tetrahedral intermediate. 

Ester hydrolysis can also be promoted by nucleophilic catalysis. If a component of the reaction system is a more effective nucleophile toward the carbonyl group than hydroxide ion or water under a given set of conditions, an acyl-transfer reaction can take place to form an intermediate ... 

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-... 

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