Fischer esterifications

Recent reviews (31-34,36,37,51) provide a comprehensive survey of the types of heterogeneous catalytic reactions investigated at supercritical conditions including alkylation, amination, cracking, disproportionation, esterification, Fischer-Tropsch synthesis, hydrogenation, isomerization, and oxidation. Table 2 summarizes reported investigations under these classes of reaction. Some of these examples are described here to show how to systematically exploit supercritical media in heterogeneous catalysis. 

Fig. 23(B) shows a modification of the reflux assembly to allow a gas to be passed through the boiling liquid cf. Fischer-Speier esterification, p. 104). The inlet-tube A fits into a three-necked adaptor shown in Fig. 22(J). The stopper B can be replaced by a dropping-funnel, etc.

As a general rule esterification by the Fischer-Speier method should be carried out using absolute cthanob in the following preparation of ethyl benzoate, however, the yield is not sensibly affected by the use of the cheaper rectified spirit. 

The mother liquors from the washings and recrystallisations are saved for the recovery of the 4-nitrophthalic acid. The combined mother liquors ore concentrated to a small bulk and the acid is extracted with ether. Upon esterification by the Fischer - Speier method, the 3-nitro acid forms only the acid ester and may be removed by shaking the product with sodium carbonate solution, whilst the neutral ester of 4-iiitrophthalic acid remains unaffected. Hydrolysis of the neutral ester gives the pure 4-nltrophthalio acid, m.p. 165°. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

Acid catalyzed condensation of an alcohol and a carboxylic acid yields an ester and water and IS known as the Fischer esterification... 

Fischer esterification is reversible and the position of equilibrium lies slightly to the side of products when the reactants are simple alcohols and carboxylic acids When the Fis cher esterification is used for preparative purposes the position of equilibrium can be made more favorable by using either the alcohol or the carboxylic acid m excess In the following example m which an excess of the alcohol was employed the yield indicated IS based on the carboxylic acid as the limiting reactant... 

For steric reasons the order of alcohol reactivity m the Fischer esterification is CH3OH > primary > secondary > tertiary... 

The mechanisms of the Fischer esterification and the reactions of alcohols with acyl chlorides and acid anhydrides will be discussed m detail m Chapters 19 and 20 after some fundamental principles of carbonyl group reactivity have been developed For the present it is sufficient to point out that most of the reactions that convert alcohols to esters leave the C—O bond of the alcohol intact... 

From carboxylic acids (Sections 15 8 and 19 14) In the pres ence of an acid catalyst alco hols and carboxylic acids react to form an ester and water This IS the Fischer esterification... 

Hydrolysis (Sections 20 10 and 20 11) Ester hydrolysis may be catalyzed either by acids or by bases Acid catalyzed hydrolysis is an equilibrium controlled process the reverse of the Fischer esterification Hydrolysis in base IS irreversible and is the method usual ly chosen for preparative purposes... 

Section 2010 Ester hydrolysis can be catalyzed by acids and its mechanism (Figure 20 4) is the reverse of the mechanism for Fischer esterification The reaction proceeds via a tetrahedral intermediate... 

Fischer esterification m which a phenol and a carboxylic acid condense m the pres ence of an acid catalyst is not used to prepare aryl esters... 

Carboxyl groups of ammo acids and peptides are normally protected as esters Methyl and ethyl esters are prepared by Fischer esterification Deprotection of methyl and ethyl esters is accomplished by hydrolysis m base Benzyl esters are a popular choice because they can also be removed by hydrogenolysis Thus a synthetic peptide protected at both... 

Fingerprint region (Section 13 20) The region 1400-625 cm of an infrared spectrum This region is less character istic of functional groups than others but varies so much from one molecule to another that it can be used to deter mine whether two substances are identical or not Fischer esterification (Sections 15 8 and 19 14) Acid cat alyzed ester formation between an alcohol and a carboxylic acid... 

The ethyl 7-veratrylbutyrate, b.p. 203-207°/20 mm., is obtained in 80% yield by esterification of 7-veratrylbutyric acid by the Fischer-Speier method. The 7-veratrylbutyric acid is prepared by the method of E. L. Martin from /3-(3,4-dimethoxy-benzoyl)-propionic acid. 

Although the term ester, used without a modifier, is normally taken to mean an ester of a car boxylic acid, alcohols can react with inorganic acids in a process similar- to the Fischer esterification. The products are esters of inorganic acids. For example, alkyl nitrates are esters formed by the reaction of alcohols with nitric acid. 

Fischer esterification (Section 15.8) Alcohols and carboxylic acids yield an ester and water in the presence of an acid catalyst. 

We have seen this theme before in Section 19.14 when we presented the mechanism of the Fischer esterification. As was the case then, formation of the tetrahedral intermediate is rate-determining. 

Section 20.7 Esters occur naturally or are prepared from alcohols by Fischer esterification or by acylation with acyl chlorides or acid anhydrides (see Table 20.3). 

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