Resonance, enol formation

Mechanism of base-catalyzed enol formation. The intermediate enolate ion, a resonance hybrid of two forms, can be protonated either on carbon to regenerate the starting keto tautomer or on oxygen to give an enol. 

Here, the ylid form can be stabilized by enolate formation and by d-orbital resonance, which explains the moderate value of pK. The possibility of pseudo-base formation can be excluded (75) by comparison with u.v. spectra. Thus, polarography made it possible to detect and characterize stable ylid formation in solutions several years before these ylids were isolated. 

Gas-phase transfers of hydride from methoxide to C02, CS2 and S02 have been observed by the flowing afterglow technique (Bierbaum et al., 1984) and by Fourier transform ion cyclotron resonance spectroscopy (FT-ICR) (Sheldon et al., 1985). With aldehydes and ketones, the normal gas-phase reaction with methoxide is enolate formation, but FT-ICR methods have been used to demonstrate reduction of non-enolizable aldehydes including benzaldehyde, pivalaldehyde, and 1-adamantylaldehyde. 

Baae-catalyzed enol Formation occurs by an acid-base reamion between catalyst and carbonyl compound. The carbonyl compound acta as a weak protre acid and donates- one of its e. The rss-uJtant anion—an enolatc ion —is then reprotonated to yield a neutral compound. Since the enolate iun is a resonance hybrid of two forms, it can be proto-nated either on the or carbon to regenerate the keto tautomer or on oxygen to give the enol tautomer (Figure 22.2, p, 905). 

This carbanion certainly exists in a reversible equilibrium with both the neutral ester (XXVII) and the neutral enol (XXVIII), established by reaction of the carbanion with alcohol through the resonance forms XXV or XXVI. It is evident, however, that if the equilibrium B is not established very rapidly with inspect to A the rate of enol formation will be slower than the rate of carbanion formation. According to this interpretation, it will not be cprrccfl to say that the rate of reaction is dependent upon the rate of enoHzation of the active methylene component.14 ... 

When the following compound is treated with sodium ethoxide, nearly all of it is converted into an enolate. Draw the resonance structures of the enolate that is formed, and explain why enolate formation is nearly complete despite the use of ethoxide rather than LDA... 

The extent of resonance in carboxylic acid derivatives is also seen in their basicity (protonation at the carbonyl oxygen) and acidity (enolate formation). In all cases, protonation requires strong acid, but it gets easier as the electron-donating ability of the L group increases. Protonation is important in acid-catalyzed nucleophilic addition-elimination reactions. 

The Claisen condensation is initiated by deprotonation of an ester molecule by sodium ethanolate to give a carbanion that is stabilized, mostly by resonance, as an enolate. This carbanion makes a nucleophilic attack at the partially positively charged carbon atom of the e.ster group, leading to the formation of a C-C bond and the elimination ofan ethanolate ion, This Claisen condensation only proceeds in strongly basic conditions with a pH of about 14. 

Enolate ion formation (Section 18.6) An a hydrogen of an aldehyde or a ketone is more acidic than most other protons bound to carbon. Aldehydes and ketones are weak acids, with pK s in the 16 to 20 range. Their enhanced acidity is due to the electron-withdrawing effect of the carbonyl group and the resonance stabilization of the enolate anion. 

Figure 22.5 Mechanism of enolate ion formation by abstraction of an a proton from a carbonyl compound. The enolate ion is stabilized by resonance, and the negative charge (red) is shared by the oxygen and the a carbon atom, as indicated by the electrostatic potential map.

Besides the allylation reactions, imines can also undergo enol silyl ether addition as with carbonyl compounds. Carbon-carbon bond formation involving the addition of resonance-stabilized nucleophiles such as enols and enolates or enol ethers to iminium salt or imine can be referred to as a Mannich reaction, and this is one of the most important classes of reactions in organic synthesis.104... 

Although Eibner elucidated the structure between 1904 and 1906, it was only through IR and nuclear magnetic resonance spectroscopy (NMR) that the chro-maticity of these molecules could be attributed to keto-enol tautomerism and simultaneous hydrogen bond formation (structures 137a = 137b) [2]. 

Elimination reactions (Figure 5.7) often result in the formation of carbon-carbon double bonds, isomerizations involve intramolecular shifts of hydrogen atoms to change the position of a double bond, as in the aldose-ketose isomerization involving an enediolate anion intermediate, while rearrangements break and reform carbon-carbon bonds, as illustrated for the side-chain displacement involved in the biosynthesis of the branched chain amino acids valine and isoleucine. Finally, we have reactions that involve generation of resonance-stabilized nucleophilic carbanions (enolate anions), followed by their addition to an electrophilic carbon (such as the carbonyl carbon atoms... 

The racemization process involves removal of the a-hydrogen to form the enolate anion, which is favoured by both the enolate anion resonance plus additional conjugation with the aromatic ring. Since the a-protons in esters are not especially acidic, the additional conjugation is an important contributor to enolate anion formation. The proton may then be restored from either side of the planar system, giving a racemic product. 

The mechanism of imine formation is standard, as seen in the other examples. The cyclization reaction is then like the Mannich reaction, attack of an enol on to the iminium cation. This time though, the nucleophile is provided by the resonance effect from the phenol system. 

Experimentally, x values for gaseous lithium halides were determined as early as 1949 by molecular beam resonance experiments In solution, the quadrupolar interaction of ethyUithium and of t-butyllithium were investigated in 1964 . It was found that tetrameric and hexameric aggregates have different interactions. In the solid state x of tetrameric methyl- and ethyUithium was determined in 1965 and 1966 , and for lithium formate in 1972 . However, it was not untU Jackman started his investigations of lithium enolates and phenoxides in solution that the quadrupolar interaction was used in a systematic fashion to obtain structural information . 

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