Esters resonance effects

Clearly, the nex.t step will be to investigate the physicochemical effects, such as charge distribution and inductive and resonance effects, at the reaction center to obtain a deeper insight into the mechanisms of these biochemical reactions and the finer details of similar reactions. Here, it should be emphasized that biochemical reactions arc ruled and driven basically by the same effects as organic reactions. Figure 10.3-22 compares the Claisen condensation of acetic esters to acctoacctic esters with the analogous biochemical reaction in the human body. 

Another example of enhanced sensitivity to substituent effects in the gas phase can be seen in a comparison of the gas-phase basicity for a series of substituted acetophenones and methyl benzoates. It was foimd that scnsitivtiy of the free energy to substituent changes was about four times that in solution, as measured by the comparison of A( for each substituent. The gas-phase data for both series were correlated by the Yukawa-Tsuno equation. For both series, the p value was about 12. However, the parameter r" ", which reflects the contribution of extra resonance effects, was greater in the acetophenone series than in the methyl benzoate series. This can be attributed to the substantial resonance stabilization provided by the methoxy group in the esters, which diminishes the extent of conjugation with the substituents. 

In the acidic and alkaline hydrolysis rates of the same ester, the steric and resonance effects. re the same. 

Carbonates, like esters, can be cleaved by basic hydrolysis, but generally are much less susceptible to hydrolysis because of the resonance effect of the second oxygen. In general, carbonates are cleaved by taking advantage of the properties of the second alkyl substituent (e.g., zinc reduction of the 2,2,2-trichloroethyl carbonate). The reagents used to introduce the carbonate onto alcohols react readily with amines as well. As expected, basic hydrolysis of the resulting carbamate is considerably more difficult than basic hydrolysis of a carbonate. 

Taft, following Ingold," assumed that for the hydrolysis of carboxylic esters, steric, and resonance effects will be the same whether the hydrolysis is catalyzed by acid or base (see the discussion of ester-hydrolysis mechanisms. Reaction 10-10). Rate differences would therefore be caused only by the field effects of R and R in RCOOR. This is presumably a good system to use for this purpose because the transition state for acid-catalyzed hydrolysis (7) has a greater positive charge (and is hence destabilized by —I and stabilized by +1 substituents) than the starting ester. 

In a, 3-unsaturated ketones, nitriles, and esters (e.g., 125), the y hydrogen assumes the acidity normally held by the position a to the carbonyl group, especially when R is not hydrogen and so cannot compete. This principle, called vinylology, operates because the resonance effect is transmitted through the double bond. However, because of the resonance, alkylation at the a position (with allylic rearrangement) competes with alkylation at the y position and usually predominates. 

Finally, in this account of multiparameter extensions of the Hammett equation, we comment briefly on the origins of the a, scale. This had its beginning around 1956 in the a scale of Roberts and Moreland for substituents X in the reactions of 4-X-bicyclo[2.2.2]octane-l derivatives. However, at that time few values of o were available. A more practical basis for a scale of inductive substituent constants lay in the o values for XCHj groups derived from Taft s analysis of the reactivities of aliphatic esters into polar, steric and resonance effects . For the few o values available it was shown that o for X was related to o for XCHj by the equation o = 0.45 <7. Thereafter the factor 0.45 was used to calculate c, values of X from o values of XCH2 . ... 

Note that we can write a similar resonance picture for esters, and we shall actually need to invoke this when we discuss enolate anions (see Section 10.7). However, electron donation from oxygen is not as effective as from the less electronegative nitrogen. We shall also see that this resonance effect in amides has other consequences, such as increased acidity of the amide hydrogens (see Section 10.7) and stereochemical aspects of peptides and proteins (see Section 13.3). In addition, the amide derivatives have... 

In this work the rates of alkaline hydrolysis in 70% dioxan-water and those of acid-catalyzed ester formation in methanol were compared for the cis (31a) and trans (31b) substituted compounds. This was expected to isolate the steric effects of the cis substituents, since inductive and resonance effects should be similar in the cis and the trans compounds. The results are summarized in Table 34, and show the trend already observed for orf/m-substituted... 

Numerous authors189-191 have compared the reactions of Fischer carbene complexes with nucleophiles to the corresponding reactions of carboxylic esters.183,185-187 Our view is that there is much more resemblance between the reactions of Fischer carbene complexes and SNV reaction than between the reactions of Fischer carbene complexes and reactions with esters because in the latter reactions there are no strong resonance effects. 

The electronic properties of both alkyl [5] and aryl alcohols [6] play a clearly definable role in ester formation, with formation constants decreasing with increase in electron withdrawing ability of the ligand. For both types of ligands, the electronic influences are quite small, but the resonance effects found with the aromatic ligands indicate there are 71-electron contributions to the empty d orbitals of vanadate [6], The influences of the electronic properties of ligands on coordination mode and geometry are discussed in detail in Chapter 9. 

The following a ester radical (23) is just stabilized by the resonance effect of one ester group. This effect is not as strong, so the a ester radical (23) can be observed using ESR only at < — 30 °C, and it couples to a dimer soon at room temperature [8]. 

Nucleophilic radical, R and activated alkyl iodides, R l, which have electron-withdrawing groups, react smoothly through a SOMO-LUMO (a ) interaction to form RI and stable R as shown in Table 1.17. Here, the formed Rf is stabilized through the resonance effect by an ester or a cyano group [74]. 

Although the resonance effect is weak in esters and acid anhydrides, it explain why acid anhydrides are more reactive than esters. Acid anhydrides have two carbonyl groups and so resonance can occur with either carbonyl group (Following fig.). Due to this, the lone pair of the central oxygen is split between both groups that means that the resonance effect is split between both carbonyl groups. 

This means that the effect of resonance at any one carbonyl group is diminished and it will remain strongly electrophilic. With an ester, there is only one carbonyl group and so it experiences the full impact of the resonance effect. Therefore, its electrophilic strength will be diminished relative to an acid anhydride. 

Conjugation with an oxygen atom has much the same effect—formate esters resonate at about 8 p.p.m.—but conjugation with 7t bonds does not. The simple conjugated aldehyde below and myrte-nal both have CHO protons in the normal region (9-10 p.p.m.). 

Figure 15.14 Effects on NMR signals of the resonance effect in mesomeric forms of a carbonyl. If the carbonyl of a ketone is compared with that of an ester, then it should be noted that for the ketone, the more electropositive of the two, the carbon has less protection than the ester. In NMR the carbonyl signal for a ketone is around 205 ppm while for an ester it is around 165 ppm.

Fulling and Sih reported one of the earliest examples to exploit racemization of carboxylic acid derivatives in order to achieve a dynamic kinetic resolution1311. The anti-inflammatory drug Ketorolac was prepared by hydrolysis of the corresponding ester. Whilst most lipases afforded the undesired enantiomer preferentially, a protease from Streptomyces griseus afforded the required (S)-enantiomer of product with good selectivity. The substrate was particularly prone to racemization since the intermediate enolate is well stabilized by resonance effects, although a pH 9 7 buffer was required to achieve a useful dynamic resolution reaction. Thus the acid was formed with complete conversion and with 76 % enantiomeric excess. 

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