Alcohols Fischer esterification

Acid-catalyzed reaction between an acid and an alcohol (Fischer esterification) ... 

Esterification With Diazomethane Reaction of Acyl Chlorides With Alcohols Fischer Esterification... 

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... 

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... 

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. 

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). 

Fischer esterification (Sections 15.8 and 19.14) Acid-catalyzed ester formation between an alcohol and a carboxylic acid ... 

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. 

The net effect of Fischer esterification is substitution of an -OH group by —OR. Aii steps are reversible, and the reaction can be driven in either direction by choice of reaction conditions. Ester formation is favored when a large excess of alcohol is used as solvent, but carboxylic acid formation is favored when a large excess of water is present. 

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). 

Acid-catalyzed ester hydrolysis can occur by more than one mechanism, depending on the structure of the ester. The usual pathway, however, is just the reverse of a Fischer esterification reaction (Section 21.3). The ester is first activated toward nucleophilic attack by protonation of the carboxyl oxygen atom, and nucleophilic addition of water then occurs. Transfer of a proton and elimination of alcohol yields the carboxylic acid (Figure 21.8). Because this hydrolysis reaction is the reverse of a Fischer esterification reaction, Figure 21.8 is the reverse of Figure 21.4. 

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. 

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. 

Acid hydrolysis is the reverse of the Fischer esterification, seen earlier in the section Acid plus alcohol. Figure 12-34 illustrates the mechanism. 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (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. 

The acid-catalysed hydrolysis of an ester is the reverse reaction of the Fischer esterification. Addition of excess water drives the equilibrium towards the acid and alcohol formation. The base-catalysed hydrolysis of esters is also known as saponification, and this does not involve the equilibrium process observed for the Fischer esterification. 

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]... 

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