Sources of Esters

This pattern of increased reactivity resulting from carbonyl group protonation has been seen before in nucleophilic additions to aldehydes and ketones (Section 17.6) and in the mechanism of the acid-catalyzed esterification of carboxylic acids (Section 19.14). Many biological reactions involve nucleophilic acyl substitution and are catalyzed by enzymes that act by donating a proton to the carbonyl oxygen, the leaving group, or both. 

PROBLEM 20.8 Write the structure of the tetrahedral intermediate formed in each of the reactions given in Problem 20.7. Using curved arrows, show how each tetrahedrai intermediate dissociates to the appropriate products. 

SAMPLE SOLUTION (a) The reaction given is the acid-catalyzed esterification of methanoi by benzoic anhydride. The first step is the activation of the anhydride toward nucieophiiic addition by protonation. 

The tetrahedrai intermediate is formed by nucleophilic addition of methanol to the protonated carbonyl group. 

1 0 C = 0 / CsHb Tetrahedral Proton intermediate C=OH CsHb Methyl benzoate Benzoic Proton acid j 

Acid anhydrides are more stable and less reactive than acyl chlorides. Acetyl chloride, for example, undergoes hydrolysis about 100,000 times more rapidly than acetic anhydride at 25°C. 

Step 1 Nucleophilic addition of p-nitrophenoxide to one of the carbonyl groups of the anhydride gives the conjugate base of the tetrahedral intermediate (TI ). 

Step 2 Expulsion of acetate from TI restores the carbonyl group. 

Many esters occur naturally. Those of low molecular weight are fairly volatile, and many have pleasing odors. Esters often form a significant fraction of the fragrant oil of fruits and flowers. The aroma of oranges, for example, contains 30 different esters along with 10 carboxylic acids, 34 alcohols, 34 aldehydes and ketones, and 36 hydrocarbons. 

Among the chemicals used by insects to communicate with one another, esters occur frequently. 

Notice that (Z)-5-tetradecen-4-olide is a cyclic ester. Recall from Section 18.15 that cyclic esters are called lactones and that the suffix -olide is characteristic of lUPAC names for lactones. 

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Other Gas Reactions. Several other reactive gases or vapours were examined but found to be unsatisfactory. No ester formation ( 1745 cm"1) was found when oxidatized films were exposed to acetic acid or formic acid vapour. Alcohol/carboxylic acid reactions in the solid state have often been suggested as the source of ester products, but not substantiated (4,5). Gaseous ammonia reacted with carboxylic acid groups to give absorptions at 1550 cm"1 [-C(=0)-0 ] and 1300 cm"1 (NHi +). However, these absorptions were very broad and the method inferior to acid measurement by SF. Although N20 did not react with oxidized polyolefins, the reaction of N02 with oxi-... 

Once formed, alcohols esterify to some extent with the acids generated in an oxidation reaction. Except for lactones, esters do not appear to be generated directly in oxidation mechanisms [10, 37, 38]. The Bayer-Villiger reaction of intermediate peracids and ketones is sometimes proposed as a source of esters [39] but it appears to be too slow to be a significant source except in the case of cycloparaffins [10, 40]. The ester group and its immediate neighboring groups appear to be remarkably resistant to oxidation. 

Betula species.49 The efficient conversion of (20S,24i )-20,24-epoxydammarane-3a, 12(3,25-triol into the 25-0-,3-D-glucoside has been reported.50 The seed oil of Cacalia atriplicifolia (Compositae) is a rich source of esters of dammarenediol II.51... 

Although the partition coefficients of ABE fermentation products was smaller in MFA (1.4 to 4-fold smaller) as compared to oleyl alcohol [92], cheap sources of esters, such as palm oil, were found. Furthermore, effluents from the palm oil industry provided adequate substrates for ABE fermentations [93], and since MFA could be employed as biodiesels, coupling ABE production with MFA to yield biodiesels, thus avoiding the costly solvent recovery step, was suggested [92]. 

Malonate anions are convenient sources of ester enolates. They react with halides and a variety of other electrophiles. Acid hydrolysis of the ester followed by decarboxylation gives the mono-acid. An example of this approach used phthalic anhydride 1.178) as a starting material in a reaction with 2-aminoethanol to give 1.179. Conversion of the alcohol moiety in 1.179 to its 0-benzenesulfonate ester... 

When this reaction is carried out on the parent diethyl malonate, acetic acid results, and the process is of no practical synthetic utility. As with the synthesis of ketones starting from P-keto esters, this process is far more usefiil when combined with the alkylation reaction. One or two alkylations of malonic ester give substituted diesters that can be hydrolyzed and decarboxylated to give carboxylic acids (Fig. 19.62). Substituted acetic acids are potential sources of esters, acid halides, and any other compound that can be made from a carboxylic acid. 

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