Carbonyl condensation reaction mechanism

Active Figure 23.1 MECHANISM The general mechanism of a carbonyl condensation reaction. One partner becomes a nucleophilic donor and adds to the second partner as an electrophilic acceptor. 

The Knoevenagel reaction is a carbonyl condensation reaction of an ester with an aldehyde or ketone to yield an a,j8-unsaturated product. Show the mechanism of the Knoevenagel reaction of diethyl malonate with benzaldchyde. 

The Darzens reaction involves a two-step, base-catalyzed condensation of ethyl chloroacetate with a ketone to yield an epoxy ester. The first step is a carbonyl condensation reaction, and the second step is an SK2 reaction. Write both steps, and show their mechanisms. 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

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. 

Carbonyl condensation reactions take place between two carbonyl partners and involve a combination of nucleophilic addition and a-substitution steps. One partner (the nucleophilic donor) is converted into its enoiate ion and undergoes an a-substitution reaction when it adds as a nucleophile to tl second partner (the electrophilic acceptor). The general mechanism of a carl bonyl condensation reaction is shown in Figure 23.1. 

There are three general mechanisms by which aldehydes and ketones react. These are (i) nucleophilic addition reactions, (ii) a-substitution reactions and (iii) carbonyl-carbonyl condensation reactions. 

Walsh refers to the enzymes described in this section (which catalyze carbonyl condensation reactions involving one component that is not an aldehyde or ketone) as Claisen enzymes (6). I shall use that terminology here, although these reactions are not formally Claisen condensations, but they are distinguished by their mechanisms from the other adolases mentioned in Section III,A, 1. 

Many types of carbonyl condensation reactions have acquired specialized names, after the nineteenth-century organic chemists who first studied them. Propose mechanisms for the following named condensations. 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

Both in the laboratory and in living organisms, the reactions of carbonyl compounds take place by one of four general mechanisms nucleophilic addition, nucleophilic acyl substitution, alpha substitution, and carbonyl condensation. These... 

Mechanism of the aldol reaction, a typical carbonyl condensation. 

Tire mechanism of the Claisen condensation is similar to that of the aldol condensation and involves the nucleophilic addition of an ester enolate ion to the carbonyl group of a second ester molecule. The only difference between the aldol condensation of an aldeiwde or ketone and the Claisen condensation of an ester involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is protonated to give an alcohol product—exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution product—exactly the behavior previously seen for esters (Section 21.6). The mechanism of the Claisen condensation reaction is shown in Figure 23.5. 

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