Ester enolate ions

An alkylation reaction is used to introduce a methyl or primary alkyl group onto the a position of a ketone, ester, or nitrile by S 2 reaction of an enolate ion with an alkyl halide. Thus, we need to look at the target molecule and identify any methyl or primary alkyl groups attached to an a carbon. In the present instance, the target has an a methyl group, which might be introduced by alkylation of an ester enolate ion with iodomethane. 

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. 

O Base abstracts an acidic alpha hydrogen atom from an ester molecule, yielding an ester enolate ion,... 

Intramolecular nucleophilic addition of the ester enolate ion to the carbonyl group of the second ester at the other end of the chain then gives a cyclic tetrahedral intermediate. 

The following structure represents an intermediate formed by addition of an ester enolate ion to a second ester molecule. Identify the reactant, the leaving group, and the product. 

The procedure reported here is based on a reaction discovered by Bunnett and Creary, and was first employed for preparative purposes by Bunnett and Traber.3 It is attractive because of the high yield obtained, the ease of work-up, and the cleanliness of the reaction. The reaction is believed to occur by the SRN1 mechanism, which involves radical and radical anion intermediates.2,4 The SRN1 arylation of other nucleophiles, especially ketone enolate ions,5 ester enolate ions,6 picolyl anions,7 and arenethiolate ions,8 has potential application in synthesis. 

Although collision induced dissociation (CID) is a well-known method for investigating the structures of cations in the gas phase (McLafferty, 1983), it has been applied much less to anions (Bowie, 1986). Actually, in some cases CID has been used to study the fragmentation mechanisms of anions, such as the elimination of molecular hydrogen from alkoxide ions (Hayes el al., 1984) or the primary fragmentation routes of ester enolate ions (Froelicher et al., 1985). 

Claisen condensation reaction (Section 23.7) a nucleophilic acyl substitution reaction that occurs when an ester enolate ion attacks the carbonyl group of a second ester molecule. The product is a p-keto ester. 

The mechanism of the Claisen condensation is similar to that of the aldol condensation. As shown in Figure 23.5, the Claisen condensation involves the nucleophilic acyl substitution of an ester enolate ion on the carbonyl group of a second ester molecule. 

Dieckmann cyclization of diethyl adipate can be described by the two successive equilibria shown below. Use SpartanView to obtain the energies of diethyl adipate, the keto ester, the keto ester enolate ion, ethanol, and ethoxide anion, and calculate AH° for both steps. Which step is more favorable ... 

Subsequent research showed the SrnI mechanism to occur with many other aromatic compounds. The reaction was found to be initiated by solvated electrons, by electrochemical reduction, and by photoinitiated electron transferNot only I, but also Br, Cl, F, SCeHs, N(CH3)3, and 0P0(0CH2CH3)2 have been foimd to serve as electrofuges. In addition to amide ion, phosphanions, thiolate ions, benzeneselenolate ion (C HsSe"), ketone and ester enolate ions, as well as the conjugate bases of some other carbon acids, have been identified as nucleophiles. The SrnI reaction was observed with naphthalene, phenanthrene, and other polynuclear aromatic systems, and the presence of alkyl, alkoxy, phenyl, carboxylate, and benzoyl groups on the aromatic ring does not interfere with the reaction. ... 

For the formation and reaction of ester enolate ions see Section 9.11... 

However, the reaction works best when the ester does not contain any a-hydrogen atoms (and so cannot form an ester enolate ion). 

---