Esters resonance forms

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

Resonance forms illustrating charge delocalization in enolate of a p keto ester... 

Polyamides. The next two compounds are the amide counterparts of the esters listed under item (4). Although the values of AH j are less for the amides than for the esters, the values of T j, are considerably higher. This is a consequence of the very much lower values of AS j for the amides. These, in turn, are attributed to the low entropies of the amide in the liquid state owing to the effects of hydrogen bonding and chain stiffness arising from the contribution of the resonance form... 

Steric effects on both the amide and the acyloxyl side chain are similar. Tert-butyl and adamantyl groups on the amide side chain in 29v, 29x, 29c, and 29e (Table 2 entries 53 and 54, 63 and 65) result in lower stretch frequencies that, on average, are only 40 cm-1 higher than their precurser hydroxamic esters. Streck and coworkers have suggested that such changes in dialkyl ketones can be ascribed to destabilisation of resonance form II through steric hindrance to solvation which, in the case of tert-butyl counteracts the inductive stabilisation.127... 

The Claisen condensation is one method of synthesizing (3-dicarbonyl compounds, specifically a (3-keto ester. This reaction begins with an ester and occurs in two steps. In the first step, a strong base, such as sodium ethoxide, removes a hydrogen ion from the carbon atom adjacent to the carbonyl group in the ester. (Resonance stabilizes the anion formed from the ester.) The anion can then attack a second molecule of the ester, which begins a series of mechanistic steps until the anion of the (3-dicarbonyl compound forms, which, in the second reaction step (acidification), gives the product. 

The preparation of barbiturates illustrates many of the synthetic methods covered in this chapter. The preparation employs the reaction of urea (C0(NH2)2) with malonic ester to form barbituric acid. The general reaction is presented in Figure 15-30. The stable pyrimidine and other resonance forms help drive the reaction. By alternating the substituent at carbon number five (C5), various pharmacologically active substances can be formed. Barbital, a sedative, and phenobarbital, a sleeping aid, are shown in Figure 15-31. 

Branched iV-chlorohydroxamic esters exhibit much lower carbonyl frequencies in their IR spectra. Series of Ai-(phenylethyloxy)amides (Table 2, entries 1-7) and Af-butoxy-amides (Table 2, entries 12-16) show a clear movement to lower carbonyl stretch frequencies with branching alpha to the carbonyl, in accord with greater inductive stabilization of the polar resonance form III of the carbonyl (Figure la). Neopentyl (entry 17) is a special case. While the group should contribute much more inductive stabilization than ethyl, its carbonyl stretch frequency is higher. Similar changes have been noted in the IR spectra of branched ketones and have been ascribed to a degree of steric hindrance to solvation and therefore destabilization of the polar resonance form Dl". ... 

Amides. Although similar to esters in terms of being a functional derivative of a carboxylic acid, amides, unlike esters, are relatively metabolically stable. In general, amides are stable to acid- and base-catalyzed hydrolysis. This stability is related to the overlapping electron clouds within the amide functionality and the corresponding multiple resonance forms. Amidases are enzymes that can catalyze the hydrolysis of amides. Nevertheless, amides are much more stable than esters. 

Mixtures of isomeric di-ALoxides are generally obtained when 5(6)-substituted benzofurazan 1-oxides (51) are used in the Beirut reaction52-54 however, only 7-substituted 2-cyano-3-phenylquin-oxaline 1,4-dioxides (52) were isolated from benzoylacetonitrile (PhCOCH2CN).55 The di-AAoxide mixtures obtained from reaction with acetonyl methyl sulfide (MeCOCH2SMe) were analyzed by H nuclear magnetic resonance (NMR) analysis of the mixed hydroxamic esters (53) formed by hydrolysis and methylation of the primary products.52... 

Uncatalyzed hydrolysis of a peptide linkage is very slow with f1/2 at neutral pH and 25°C of 300-600 years.189 Both acids and bases catalyze hydrolysis, but enzymes are needed for rapid digestion. The carbonyl group C=0 is highly polarized, with the resonance form C+-0 contributing substantially to its structure. An attack by a base will take place readily on the electrophilic carbon atom. While the reactivity of the carbonyl group in esters and amides is relatively low... 

Ground state /-effects of silicon may be responsible for the elongated C(alkyl)-O(ester) bond in n.s-3-trimelhylsilylcyclohexyl p-nitrobenzoate 59 relative to the silicon-free derivative. It is suggested that the ground state /-effect could be due either to homohyperconjugation, 60, or to inductively enhanced C—C hyperconjugation where the trimethylsilyl substituent increases the importance of the resonance form 61 relative to the silicon-free derivative. 

In contrast, the esters 145 and 167 show no significant effects on the C-OR bond distance. These structural effects are consistent with a significant percaudal interaction, as represented by the resonance form 168. 

Fig. 3.18. Mechanistic details on the transition-metal catalyzed (here Cu-catalyzed) cyclopropanation of styrene as a prototypical electron-rich alkene. The more bulky the substituent R of the ester group C02R, the stronger is the preference of transition state A over D and hence the larger the portion of the trans-cyclo-propane carboxylic acid ester in the product mixture.—The zwitterionic resonance form B turns out to be a better presentation of the electrophilic character of copper-carbene complexes than the (formally) charge-free resonance form C or the zwitterionic resonance form (not shown here) with the opposite charge distribution ( a to the C02R substituent, on Cu) copper-carbene complexes preferentially react with electron-rich alkenes.

Base-mediated ester hydrolyses have a high driving force. This is because of the acid/base reaction between the carboxylic acid formed in the reaction, and the base used as the reagent. The resonance stabilization of the carboxylate is approximately 30 kcal/mol, which means a gain of about 16 kcal/mol compared to the starting material, the carboxylic ester (resonance stabilization 14 kcal/mol according to Table 6.1). Accordingly, the hydrolysis equilibrium lies completely on the side of the carboxylate. 

Be this as it may, lithium attempts to bind to several bonding partners the structural consequences for the enolates of a ketone, an ester, and an amide are shown in Figure 13.2 In contrast to the usual notation, these enolates are not monomers at all The heteroatom that carries the negative charge in the enolate resonance form is an excellent bonding partner such that several of these heteroatoms are connected to every lithium atom. Lithium enolates often result in tetramers if they are crystallized in the absence of other lithium salts and in the absence of other suitable neutral donors. The lithium enolate of fert-butyl methyl ketone, for example, crystallizes from THF in the form shown in Figure 13.3. 

Resonance form B identifies it as a formylated ester- or lactone enolate and resonance form... 

The enhanced reactivity of thioesters results from two major differences. First, the resonance stabilization of a thioester is less than that of an ester. In the thioester, the second resonance form involves overlap between a 2p orbital on carbon and a 3p orbital on sulfur (Figure 21-12). These orbitals are different sizes and are located at different distances from the nuclei. The overlap is weak and relatively ineffective, leaving the C — S bond of a thioester weaker than the C—O bond of an ester. 

Acidities of / -Dicarbonyl Compounds Table 22-1 compares the acidities of some carbonyl compounds with the acidities of alcohols and water. Notice the large increase in acidity for compounds with two carbonyl groups beta to each other. The a protons of the jS-dicarbonyl compounds are more acidic than the hydroxyl protons of water and alcohols. This enhanced acidity results from increased stability of the enolate ion. The negative charge is delocalized over two carbonyl groups rather than just one, as shown by the resonance forms for the enolate ion of diethyl malonate (also called malonic ester). 

Reaction of the acid with diazomethane (CH N ) gives methyl esters. Diazomethane is a 1,3-dipolar molecule, the structure of which can be written in a number of resonance forms (Scheme 3.57a). The reaction with a carboxylic acid is accompanied by the loss of nitrogen gas (Scheme 3.57b). 

When esters are protonated at the carbonyl group, there are three resonance forms two corresponding to the ones that form with aldehydes and ketones and a third with positive charge on the alkylated oxygen. 

Prelab Exercise Draw the complete mechanism for the nitration of methyl benzoate. Show the resonance forms that make the methyl ester group a meta director and deactivator of the aromatic ring. 

When a hydrogen atom is flanked by two carbonyl groups, its acidfl is enhanced even more. Table 22.1 thus shows that compounds such as 1,3-diketones (/3-diketones), 3-oxo esters ( -keto esters), and 1,3-diesters are more acidic than water. This enhanced acidity of /3-dicarbonyl compounds is due to the fact that the resultant enolate ions are stabilized by delocalization of the negative charge over two carbonyl groups. The enolate ion of 2,4-pentanedione, for example, has three resonance forms. Similar resonance forms can be drawn for other doubly stabilized enolate ions. 

Among the salts in the ascorbate series is also Ba 2-O-sulfonato-L-ascorbate dihydrate that is derived from the ascorbic acid 2-sulfate ester. This biologically important compound (17) was much debated because it was diflScult to decide whether the sulfate group was attached to C2 or C3. The structural analysis by McClelland (18) proved the site to be at C2 as shown in Figure 7. The bond lengths, angles, and resonance forms are clearly similar to those of the simple ascorbate anions irrespective of the effect of the sulfate group attached to C2. 

---