Esters from carboxylic acid and alcohol

Preparation of carboxylic esters from carboxylic acids and alcohols H+ R-C-OH + R OH R-C-OR +H20 II II 0 0... 

You can t make esters from carboxylic acids and alcohols under basic conditions because the base deprotonates the carboxylic acid (see p. 288). However, you can reverse that reaction and hydrolyse an ester to a carboxylic acid (more accurately, a carboxylate salt) and an alcohol. 

Esters from carboxylic acids and alcohols under acid catalysis the Aac2 and Ancl mechanism... 

Esters from Carboxylic Acids and Alcohols via Hydroxy Group Activation (HGA)... 

Diphenylammonium triflate, toluene, 80°C, 33-97% yield. This catalyst can also be used to prepare esters from carboxylic acids and alcohols, 78-96%... 

The Yamaguchi esterification utilises 2,4,6-trichlorobenzoyl chloride, also known as the Yamaguchi reagent, to form esters from carboxylic acids and alcohols. 

N 0 Me 0 From hydroxymethyl polystyrene by treatment with COClj, HjNNHCOjMe and NBS or Cl,.2i Mitsunobu reactions esters from carboxylic acids and alcohols lactones from hydroxy acids A/-aUcylation of phthalimides, a-alkylation of cyanoacetate carbodiimides from thioureas. ... 

A-Acyl-4-pyridones can serve as useful acyl group transfer reagents for the esterification of alcohols in >80% yields.Two notable points about these reagents are their effectiveness in the preparation of formate esters (c/. ref. 157), and their much greater rate of reaction with primary alcohols, (c/. ref. 147). Thioesters and amides can also be prepared from such pyridones by reaction with thiols or amines, respectively. Other useful reagents for the direct formation of esters from carboxylic acids and alcohols are 2-fluoropyridinium salts in the presence of caesium fluorideand certain benzoisothiazole derivatives. Primary alcohols can be esterified with 2,2 -bipyridyl-6-yl carboxylates and CsF. Selective esterification of a primary alcohol in the presence of a secondary alcohol can be achieved in acceptable yields with this reagent (c/. ref. 144). 

Very important compounds are the carboxylic acids and their derivatives, which can be formally obtained by exchanging the OH group for another group. In fact, derivatives of this type are formed by nucleophilic substitutions of activated intermediate compounds and the release of water (see p. 14). Carboxylic acid esters (R-O-CO-R ) arise from carboxylic acids and alcohols. This group includes the fats, for example (see p.48). Similarly, a carboxylic acid and a thiol yield a thioester (R-S-CO-R ). Thioesters play an extremely important role in carboxylic acid metabolism. The best-known compound of this type is acetyl-coenzyme A (see p. 12). 

Esters can be prepared from carboxylic acids and alcohols provided an acidic catalyst is present,... 

Esters, RC02R, are formed from carboxylic acids and alcohols in the presence of acid catalysts. The key step in esterification is the nucleophilic attack of a neutral alcohol molecule, R OH, at the carbonyl carbon of the conjugate acid of the carboxylic acid, RC(OH)2 , 6 ... 

Since esters are derived from carboxylic acids and alcohols, they are named by first identifying the alcohol-related part and then the acid-related part, using the -ate ending. Ethyl acetate, for example, is the ester derived from ethanol and acetic acid. 

Further examples of the reaction ROH - R COOR are included in Section 107 (Esters from Carboxylic Acids and Acid Halides) and Section 45A (Protection of Alcohols and Phenols). 

You remember, of course, that esters can be made from carboxylic acids and alcohols under acid catalysis, so you might expect them to use this type of method. On a small scale, it s usually better to convert the acid to an acyl chloride before coupling with an alcohol, using pyridine (or DMAP + Et3N) as a base this type of reaction might have been a reasonable choice too. 

Under almost anhydrous conditions in organic medium, lipases can be used in the reverse mode for direct ester synthesis from carboxylic acids and alcohols, as well as transesterifications (acyl transfer reactions) which can be divided into alcoholysis (ester and alcohol), acidolysis (ester and acid), and interesterification (ester-ester interchange). The direct esterification and alcoholysis in particular have been most frequently used in asymmetric transformations involving lipases. The parameters that influence enzymatic catalysis in organic solvents have been intensively studied and discussed. ... 

Gancet, C Preparation of Esters of Carboxylic Acids Directly From Carboxylic Acids and Alcohols Using a Catalyst System Comprising a Sulfonic Acid and a Polymer-Bound Tertiary Amine. European Patent 1,167,337, Jan 2, 2002. 

In these reactions, hydrolysis of diphenyl and triaryl phosphites to monoaryl phosphites and phenol was coupled by dehydration between carboxylic acids and amines or alcohols to the corresponding amides and esters. Therefore, the reaction can be generalized as a hydrolysis-dehydration reaction (Scheme 2). The concept of the hydrolysis-dehydration reaction using phosphites has been drown to be applicable also to reactions with other phosphorus compounds such as phosphinites, phos-phonites and phosphorates s Aryl esters of these phosphorus compounds are effective as condensing agents in the production of carboxylic amides and esters (from carboxylic acids and amines or alcohols, respectively) whereas alkyl esters are ineffective (Eqs. (1-3)) ... 

A method of esterification introduced by Meyer807 is to dissolve the carboxylic acid in an excess of concentrated sulfuric acid (if necessary with warming) and to treat the solution cautiously with a small excess of the requisite alcohol when the reaction, which is often violent, ceases—if the mixture does not become warm, it must be heated—the solution is poured on solid sodium carbonate and worked up. This method has been used for esterification of sterically hindered acids and for carboxy derivatives of nitrogenous heterocycles, also for preparation of acetonedicarboxylic esters from citric acid and alcohols.808... 

Transesterification. Ethyl esters from carboxylic acids and acetic esters of benzylic alcohols are obtained in the catalyzed transesterification processes, using ethyl acetate as the donor of ethoxy or acetyl group. 

Sn2 nucleophilic substitutions take place in scC02. The presence of silica-supported onium salts 42 as a phase-transfer catalyst enhances the reaction (Scheme 72). Esters formation from carboxylic acids and alcohols via dehydration also proceeds in scC02. The conversion increases as the CO2 pressure increases. A single homogeneous phase is obtained around the critical point, at which the conversion is maximized. 

In fact, acetal formation is even more difficult than ester formation while the equilibrium constant for acid-catalysed formation of ester from carboxylic acid plus alcohol is usually about 1, for acetal formation from an aldehyde and ethanol (shown above), the equilibrium constant is fC = 0.0125. For ketones, the value is even lower in fact, it is often very difficult to make the acetals of ketones (sometimes called ketals) unless they are cyclic (we consider cyclic acetals later in the chapter). However, there are several techniques that can be used to prevent the water produced in the reaction from hydrolysing the product. 

Explain why direct ester formation from carboxylic acids and alcohols works in acid solution but not in basic solution. By contrast, ester formation from alcohols and acid anhydrides or chlorides is commonly carried out in basic solution in the presence of bases such as pyridine. Why does this work. ... 

The structure and nomenclature of sulfonate esters (see 113, 114, or 115) are described in Chapter 20 (Section 20.11.2). It is also true that sulfonate esters are good leaving groups in the substitution reactions described in this chapter (see Section 11.2.4). Sulfonate esters are prepared by the reaction of sulfonic acids with alcohols—much the way that carboxylic acid esters are prepared from carboxylic acids and alcohols (described in Chapter 20, Section 20.11.2). More commonly, sulfonate esters are prepared by the reaction of a sulfonyl chloride (see 112) with an alcohol. This reaction is also described in Chapter 20. This section presents only a simple preview of that chemistry, with the goal of showing that it is easy to convert alcohols into sulfonate esters, which are then useful as leaving groups in substitution reactions. The formal mechanism of these reactions will be discussed in Chapter 20. 

Just as esters are formed from carboxylic acids and alcohols in the presence of dicyclohexylcarbodiimide (DCC see Section 20.5.4), so amides are formed from amines (or ammonia) and carboxylic acids. The mechanism is identical to that presented for 77 80 using DCC, but the nucleophile is an amine rather than... 

Carboxylic acids are used as intermediates in the preparation of esters, amides, acid anhydrides, and acid chlorides. Esters are formed from carboxylic acids and alcohols when the mixture is heated in the presence of a mineral acid... 

As seen in Scheme 8.55, alcohols react,reversibly, with carboxylic acids to produce esters and water. As will be discussed later (Chapter 10), but should be clear from the scheme, the hydrolysis (reaction with water) of esters produces carboxylic acids and alcohols. In a similar vein, if an ester (such as methyl ethanoate [methyl acetate, CH3CO2CH3],Table 8.6, item 17) is treated with an excess of alcohol (such as cyclo-hexanol,Table 8.6, item 17) in the presence of an acid catalyst and (generally) heated at a temperature above the distillation temperature of the alcohol with which the acid is esterilied, ester interchange can be effected (Scheme 8.58) through the addition of the higher boiling alcohol to the carbon of the carbonyl followed by expulsion of the lower boiling one. 

Rationalize why esters are most effectively formed with acid catalysis from carboxylic acids and alcohols, but more effectively hydrolyzed under basic conditions. 

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