Ethyl ester of benzoic acid

Preparation 201.—Ethyl Benzoate (Ethyl ester of benzoic acid). 

Organic chemists have studied the influence of substituents on various reactions for the better part of a century. Linear free energy relationships have played an important role in this pursuit by correlating equilibrium and rate processes. One of the earliest examples is now known as the Hammett equation. It emerged from the observation that the acidities of benzoic acids correlated with the rates at which ethyl esters of benzoic acids hydrolyzed. The relationship was expressed as follows in which K represents an equilibrium constant and k is a rate constant. The proportionality constant, m, is the slope of the log-log data plot for the two processes. 

The third case is in many ways the most interesting. We have seen that the alkaline hydrolysis of ethyl esters of benzoic acids (ArCC Et) has a p value of +2.6 and that this is a reasonable value for a reaction involving nucleophilic attack on a carbonyl group conjugated with the aromatic ring. The hydrolysis of the same esters in acid solution, which also involves nucleophilic attack on the same carbonyl group, has a p value of+0.1. In other words, all these esters hydrolyse at the same rate in acid solution. Neither of the previous explanations will do. We need to see the full mechanism to explain this remarkable result. 

Perfumes, Flavors, Cosmetics, and Soap. Many naturally occurring esters in essential oils and some synthetic esters are important fragrance and flavor compounds (61,62). They are used in perfumes, flavors, cosmetics, soaps, detergents, and air fresheners. Benzyl, butyl, ethyl, methyl, and phenyl esters of benzoic acid are used as flavors, perfumes, and food preservatives. Glyceryl 4-aminobenzoate [136-44-7] and 2-ethyUiexyl 4-dimethylaminobenzoate [21245-02-3] are used in cosmetic sunscreen preparations. Alkyl esters of 4-hydroxybenzoic acid, called parabens, have been used under various names for fungus infections of the skin, and as preservatives in lotions and creams (101). Soap and cosmetic fragrances use large amounts of amyl and benzyl saHcylate. Benzyl saHcylate [118-58-1] is also used in deodorant sprays. 2-Ethylhexyl saHcylate [118-60-5] and 2-ethylhexyl 4-methoxycinnamate [5466-77-3] are used in sunscreen formulations (102). 

Interesting data are available for three glycolic acid esters of benzoic acid, namely methyl, ethyl, and benzyl O-benzoylglycolate (8.48, R = Ph,... 

Interest in the kinetics of alkaline hydrolysis of esters in DMSO + water mixtures was stimulated by the observation that the rate constant often increased gradually as x2 increased. This is observed, for example, in the alkaline hydrolysis of ethyl acetate. For higher esters, e.g. ethyl p-nitrobenzoate, the rate constant drops slightly at low x2 but then rises again until k/k x2 = 0) > 1 (Tommila, 1964). The rate of alkaline hydrolysis of esters of benzoic acid is accelerated when DMSO is added (Tommila and Palenius, 1963), as also is the rate of alkaline hydrolysis of 2,4-dinitrofluorobenzene. In the latter case the effect is less dramatic because the rate constant for spontaneous hydrolysis also increases (Murto and Hiiro, 1964). The rate constants also increase when DMSO is added to aqueous solution for reactions between hydroxide ions and benzyl chloride (Tommila... 

Esters.—The esters of benzoic acid are not of special importance. The methyly ethyl, phenyl and benzyl esters are found in certain plants... 

Acyloin condensation. The usual preparation of acyloins from aliphatic esters is not applicable to aromatic esters. In this case the reaction with sodium results in formation of the sodium carboxylate and a radical from the R group which undergoes further reactions. However, benzoin can be prepared in moderate yield by treatment of the trimethylsilyl ester of benzoic acid with sodium or by treatment of ethyl benzoate with sodium naphthalenide in THF at room temperature (397 yield). ... 

Ethyl or longer-chain phenyl ethers, in addition, would produce an ion of m/z 94 (C6H60+ ) via McLafferty-type rearrangement [reaction (6.29)]. The ion of m/z 93 (C6H7N+) is also prodnced from ionized 2-alkyl and 4-alkylpyridines via the McLafferty rearrangement. The m/z 105 ion (CeHsCO" "), which is produced via a-cleavage, is evidence for the presence of phenyl ketones and esters and amides of benzoic acids. Esters of benzoic acids will also produce a characteristic ion of m/z 122 as a result of the McLafferty rearrangement ... 

Ethyl benzoate hydrogen chloride as a catalyst). Pass dry hydrogen chloride (Section 11,48,1) into a 600 ml. round-bottomed flask containing 116 g. (145 ml.) of absolute ethyl alcohol, cooled in an ice bath, until the increase in weight is 6 g. Add 30 g. of benzoic acid and reflux the mixture for 4 hours. Isolate the pure ester, b.p. 212-214°, as described for Methyl Benzoate. The yield is 32 g. 

Ethyl Benzoate.—This ester has not been found, so far, to occur naturally in essential oils. It has, however, been prepared by synthetic processes, for example, by condensing ethyl alcohol with benzoic acid by means of dry hydrochloric acid gas. Its odour is very similar to that of methyl benzoate (q.v.), but not quite so strong. It is an oil of specific gravity I OfilO, refractive index 1 5055, and boiling-point 213° at 745 mm. It is soluble in two volumes of 70 per cent, alcohol. 

Kindler [Twi., 450( 1), 1926] has studied the alkaline hydrolysis of the ethyl esters of a number of substituted benzoic acids. The m-nitro compound was found to have a rate constant 63.5 times as fast as the unsubstituted compound. What relative rate constant is predicted for the reaction of p-methoxybenzoate by the Hammett equation The value based on experimental results is 0.214. 

The initial 6,ll-dihydrodibenz[b,e]oxepin-ll-one (7.1.9) is synthesized from the ethyl ester of 2-phenoxymethyl benzoic acid (7.1.7), which is easily synthesized by reacting ethyl 2-bromomethylbenzoate with phenol in the presence of a base. The resulting ester (7.1.5) is hydrolyzed into 2-phenoxymethylbenzoic acid (7.1.8), which is cyclized to 6,11-dihydrodibenz[b,e]oxepin-ll-one (7.1.9) by trifluoroacetic acid anhydride. 

Estimate the Ki0Vi values at 25°C of the following compounds based on the experimental Ki0Vi values of the indicated structurally related compounds (a) benzoic acid dimethylaminoethyl ester from benzoic acid ethyl ester (log Kiaw = 2.64), (b) the insecticide methoxychlor from DDT (log Ki0Vi = 6.20), (c) the insecticide fenthion from parathion [log Kiow = 3.83, see 111. Ex. 7.2, Answer (d)], and (d) the hormone estradiol from testosterone [log Ki0Vi = 3.32, see 111. Ex. 7.2, Answer (e)]. 

Table 12.1 Reaction Rate Constants for the Base-Catalyzed Hydrolysis of Benzoic Acid Ethyl Ester (Ethyl Benzoate) in Various Organic Solvent-Water Mixturesa...

Figure 13.15 Effects of substituents on the base-catalyzed hydrolysis of benzoic acid ethyl esters in ethanoliwater (85 15) at 25°C. Relative reaction rates are correlated with Hammet Oj constants (data from Tinsley, 1979).

Bender et al.136 have measured the rate of incorporation of, 80 from enriched water into several substituted benzoic acids. The catalyst was 0.07 M HC1, and the solvent 33% dioxan-water. The rate coefficients for exchange at 80°C are given in Table 14, which also contains a comparison of these rate coefficients with those for the hydrolysis of the corresponding ethyl esters, measured by Timm and Hinshelwood128 in 60% acetone and 60% ethanol. As noted earlier by Roberts and Urey, the absolute rates are very similar for the two reactions. Also, as expected, the exchange rate of benzoic acid, with two equivalent oxygen atoms, is almost exactly twice as fast as that of ethyl benzoate, with only one ( h.vdM< xch is 5.2 for the ester). 

If we compare the acid strengths Ka) of a series of substituted benzoic acids with the strength of benzoic acid itself (Table 26-4), we see that there are considerable variations with the nature of the substituent and its ring position, ortho, meta, or para. Thus all three nitrobenzoic acids are appreciably stronger than benzoic acid in the order ortho para > meta. A methoxy substituent in the ortho or meta position has a smaller acid-strengthening effect, and in the para position decreases the acid strength relative to benzoic acid. Rate effects also are produced by different substituents, as is evident from the data in Table 26-5 for basic hydrolysis of some substituted ethyl benzoates. A nitro substituent increases the rate, whereas methyl and methoxy substituents decrease the rate relative to that of the unsubstituted ester. 

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