Fischer esterification with

For most cases, common fluoroacyl derivatives are sufficiently reactive and selective Thus conversion of perfluoroglutaric dichloride to a monomethyl ester by methanol proceeds smoothly under the appropriate reaction conditions [17] (equation 9) Perfluorosuccinic acid monoester fluoride, on the other hand, is prepared most conveniently from perfluorobutyrolacetone [IS] (equation 10) Owing to the strong acidity of a fluonnated carboxylic acids, Fischer esterification with most aliphatic alcohols proceeds autocatalytically [79 20]... 

The substrate is a carboxylic acid and undergoes Fischer esterification with methanol. 

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... 

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. 

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). 

Normal Fischer esterification of tertiary alcohols is unsatisfactory because the acid catalyst required causes dehydration or rearrangement of the tertiary substrate. Moreover, reactions with acid chlorides or anhydrides are also of limited value for similar reasons. However, treatment of acetic anhydride with calcium carbide (or calcium hydride) followed by addition of the dry tertiary alcohol gives the desired acetate in good yield. 

Esters can also be synthesized by an acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol, a process called the Fischer esterification reaction. Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of methyl, ethyl, propyl, and butyl esters. 

Problem 21.10 Which method would you choose if you wanted to prepare cyclohexyl benzoate— Fischer esterification or reaction of an acid chloride with an alcohol Explain. 

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

Explain the observation that attempted Fischer esterification of 2.4,6-tri-methylbenzoic acid with methanol and HCl is unsuccessful. No ester is obtained, and the acid is recovered unchanged. What alternative method of esterification might be successful ... 

Fischer esterification reaction (Section 21.3) The acid-catalyzed nucleophilic acyl substitution reaction of a carboxylic acid with an alcohol to yield an ester. 

With a secure route to pentacyclic amine 2, the completion of the total synthesis of 1 requires only a few functional group manipulations. When a solution of 2 in ethanol is exposed to Pd-C in an atmosphere of hydrogen, the isopropenyl double bond is saturated. When a small quantity of HCI is added to this mixture, the hydro-genolysis of the benzyl ether is accelerated dramatically, giving alcohol 15 in a yield of 96%. Oxidation of the primary alcohol in 15 with an excess of Jones reagent, followed by Fischer esterification, gives ( )-methyl homosecodaphniphyllate [( )-1] in an overall yield of 85 % from 2. 

Examples of polyfunctional carboxylic acids esterified by this method are shown in Table I. Yields are uniformly high, with the exception of those cases (maleic and fumaric acids) where some of the product appears to be lost during work-up as a result of water solubility. Even with carboxylic acids containing a second functional group (e.g., amide, nitrile) which can readily react with the oxonium salt, the more nucleophilic carboxylate anion is preferentially alkylated. The examples described in detail above illustrate the esterification of an acid containing a labile acetoxy group, which would not survive other procedures such as the traditional Fischer esterification. 

As noted in the preceding section, one of the most general methods of synthesis of esters is by reaction of alcohols with an acyl chloride or other activated carboxylic acid derivative. Section 3.2.5 dealt with two other important methods, namely, reactions with diazoalkanes and reactions of carboxylate salts with alkyl halides or sulfonate esters. There is also the acid-catalyzed reaction of carboxylic acids with alcohols, which is called the Fischer esterification. 

This method is called the Fischer esterification. It s a condensation reaction where the loss of a water molecule accompanies the joining of the alcohol portion to the acid portion. The acid gives up the OH and the alcohol gives up the H to make the water molecule. All steps in the mechanism are reversible (that is, it establishes an equilibrium), so removing the ester as soon as it forms is helpful. Removal of the ester is normally easy since esters typically have lower boiling points than alcohols and carboxylic acids. Figure 12-20 illustrates the mechanism for the acid-catalyzed formation of an ester by the reaction of an alcohol with a Ccirboxylic acid. 

Especially for large-scale work, esters, may be more safely and efficiently prepared by reaction of carboxylate salts with alkyl halides or tosylates. Carboxylate anions are not very reactive nucleophiles so the best results are obtained in polar aprotic solvents54 or with crown ether catalysts.55 The reactivity for the salts is Na+ < K+ < Rb+ < Cs+. Cesium carboxylates are especially useful in polar aprotic solvents. The enhanced reactivity of the cesium salts is due both to high solubility and to the absence of ion pairing with the anion.56 Acetone has been found to be a good solvent for reaction of carboxylate anions with alkyl iodides.57 Cesium fluoride in DMF is another useful combination.58 Carboxylate alkylation procedures have been particularly advantageous for preparation of hindered esters that can be relatively difficult to prepare by the acid-catalyzed esterification method (Fischer esterification) which will be discussed in Section... 

Esters are produced by acid-catalysed reaction of carboxylic acids with alcohols, known as Fischer esterification. They are also obtained from acid chlorides, acid anhydrides and other esters. The preparation of esters from other esters in the presence of an acid or a base catalyst is called transesterification. All these conversions involve nucleophilic acyl suhstitu-tions (see Section 5.5.5). 

Preparation of esters Esters are obtained by refluxing the parent carboxylic acid and an alcohol with an acid catalyst. The equilibrium can be driven to completion by using an excess of the alcohol, or by removing the water as it forms. This is known as Fischer esterification. 

Transesterification Transesterification occurs when an ester is treated with another alcohol. This reaction can be acid catalysed or base catalysed. This is where the alcohol part of the ester can be replaced with a new alcohol component. The reaction mechanism is very similar to the Fischer esterification. 

Ester hydrolysis is the most studied and best understood of all nucleophilic acyl substitutions. Esters are fairly stable in neutral aqueous media but are cleaved when heated with water in the presence of strong acids or bases. The hydrolysis of esters in dilute aqueous acid is the reverse of the Fischer esterification (Sections 15.8 and 19.14) ... 

While still useful for large-scale esterification of fairly robust carboxylic acids, Fischer esterification is generally not useful in small-scale reactions because the esterification depends on an acid-catalyzed equilibrium to produce the ester. The equilibrium is usually shifted to the side of the products by adding an excess of one of the reactants—usually the alcohol—and refluxing until equilibrium is established, typically several hours. The reaction is then quenched with base to freeze the equilibrium and the ester product is separated from the excess alcohol and any unreacted acid. This separation is easily accomplished on a large scale where distillation is often used to separate the product from the by-products. For small-scale reactions where distillation is not a viable option, the separation is often difficult or tedious. Consequently Fischer esterification is not widely used for ester formation in small-scale laboratory situations. In contrast, intramolecular Fischer esterification is very effective on a small scale for the closure of hydroxy acids to lactones. Here the equilibrium is driven by tire removal of water and no other reagents are needed. Moreover the closure is favored entropically and proceeds easily. 

First convert 3-methylbenzoic acid to its ethyl ester by Fischer esterification, and then treat the ester with diethylamine to give Deet. 

Esterification with alicyclic alcohols proceeds best when the alcohol is saturated with hydrogen chloride and treated with an excess of the carboxylic acid (the Fischer-Speier method) a very impure ester results if sulphuric acid is used as the catalyst. 

Alcohols can be converted to esters by means of the Fischer Esterification Process. In this method, an alcohol is reacted with a carboxylic acid in the presence of an inorganic acid catalyst. 

Step 3 Fischer esterification (reaction of a carboxylic acid with excess alcohol and a strong acid catalyst). 

Esters, RC02R, are named as salts are the R group is named first, followed by the name of the carboxylate group (for example, CH3CO2CH2CH3 is ethyl acetate). Esters can be prepared from an acid and an alcohol, with a mineral acid catalyst (Fischer esterification). The key step of the mechanism is nucleophilic attack by the alcohol on the protonated carbonyl group of the acid. Many esters are used as flavors and perfumes. 

Write the steps in the mechanism for the acid-catalyzed (Fischer) esterification of a given carboxylic acid with a given alcohol. 

This reaction, known as Fischer esterification, requires the presence of an acid catalyst. Because the carboxylic acid and the ester have similar reactivities, the reaction is useful only if a method can be found to drive the equilibrium in the direction of the desired product—the ester. In accord with Le Chatelier s principle, this is accomplished by using an excess of one of the reactants or by removing one of the products. An excess of the alcohol is used if it is readily available, as is the case for methanol or ethanol. Or water can be removed by azeotropic distillation with a solvent such as toluene. 

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