Carboxylic acids, with alcohols

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. 

Although the ability of microwaves (MW) to heat water and other polar materials has been known for half a century or more, it was not until 1986 that two groups of researchers independently reported the application of MW heating to organic synthesis. Gedye et al. [1] found that several organic reactions in polar solvents could be performed rapidly and conveniently in closed Teflon vessels in a domestic MW oven. These reactions included the hydrolysis of amides and esters to carboxylic acids, esterification of carboxylic acids with alcohols, oxidation of alkyl benzenes to aromatic carboxylic acids and the conversion of alkyl halides to ethers. 

Because amorphous carbon as graphite heats up strongly under MW irradiation [4], its use as a sensitizer has been widely reported [5-10] (Sect. 7.1). Recently, MW-as-sisted esterification of carboxylic acids with alcohols was performed on activated carbon in good yields (71-96%) [98]. For our part, when charcoal powder was used as a support, we had difficulty in desorbing the reaction products [15]. Even with a continuous extractor, the desorption was never quantitative. The desorption of reaction products from graphite powder is much easier than from amorphous carbon powder. 

More recently, the fixation efficiency on cotton of Cl Reactive Red 177 (7-43) and its 4-carboxyphenylazo analogue in the presence of various carbodiimides (including 7-44 and 7.45) was investigated, as well as homogeneous reactions of selected carboxylic acids with alcohols (including acetylcellulose in acetone). The carboxylated dye reacted more effectively with cotton cellulose in the presence of cyanamide rather than dicyandiamide,... 

Mechanism of esterification of carboxylic acids The esterification of carboxylic acids with alcohols is a kind of nncleophilic acyl snbstitntion. Protonation of the carbonyl ojq gen activates the carbonyl gronp towards nncleophilic addition of the alcohol. Proton transfer in the tetrahedral intermediate converts the hydrojq l group into - 0H2 group, which, being a better leaving group, is eliminated as neutml water molecule. The protonated ester so formed finally loses a proton to give the ester. 

Esters are usually prepared by esterification of carboxylic acids with alcohols. Industrial procedures depend on the physical properties of the esters concerned. Biosynthetic methods may be applied to produce natural esters for flavor purposes [24]. 

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). 

Taft based his steric effect constants on the assumption that rates of esterification of carboxylic acids with alcohols and of acid catalyzed hydrolysis of carboxylate... 

Esters are compounds formed by the reaction of carboxylic acids with alcohols, and they have a general structural formula of ... 

The Lewis or Bnynstedt acid-catalyzed esterification of carboxylic acids with alcohols to give esters is a typical reaction in which the products and reactants are in equilibrium. 

The O-alkylation of carboxylates is a useful alternative to the acid-catalyzed esterification of carboxylic acids with alcohols. Carboxylates are weak, hard nucleophiles which are alkylated quickly by carbocations and by highly reactive, carbocation-like electrophiles (e.g. trityl or some benzhydryl halides). Suitable procedures include treatment of carboxylic acids with alcohols under the conditions of the Mitsunobu reaction [122], or with diazoalkanes. With soft electrophiles, such as alkyl iodides, alkylation of carboxylic acid salts proceeds more slowly, but in polar aprotic solvents, such as DMF, or with non-coordinating cations acceptable rates can still be achieved. Alkylating agents with a high tendency to O-alkylate carboxylates include a-halo ketones [42], dimethyl sulfate [100,123], and benzyl halides (Scheme 6.31). 

Esterification of carboxylic acids with alcohols, including bulky secondary ones, by equimolar di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine in toluene solvent at room temperature followed by addition of a catalytic amount of hafnium(IV) trifluoromethanesulfonate, Hf(OTf)4, afforded the corresponding esters in good to high yields. In step 1 (Scheme 1), interaction of the acid and 2-DTC (1) produces the thienyl ester (2) with evolution of CO2 and formation of 2(5H)-thiophenone (3). In step 2, the added Hf(OTf)4 forms with (2) an activated complex (4), alcoholysis of which yields the ester (5) and a further molecule of 2(5H)-thiophenone.1 The procedure was also effective for converting [Pg.48]

Table V summarizes several reactions that have been demonstrated on a laboratory scale 1 know of no industrialized chemical process using Nafion as a superacid catalyst. Although many of the reactions were carried out with stirring a mixture of reactants and Nafion-H, several alkylation, disproportionation, rearrangement, and esterification reactions were performed by means of the flow-reaction method in the liquid or gas phase. For instance, in the esterification of carboxylic acids with alcohols, when a mixture of the acid and alcohol was allowed to flow over a Nafion-H catalyst at 95-125°C with a contact time 5 s, high yields, usually S90%, of the corresponding ester were obtained (82). It had been found that no reactivation of the catalyst was needed because the catalytic activity of the Nafion remained unchanged for prolonged periods of operation.

The Aac2 mechanism (Figure 6.22) of ester hydrolysis represents an SN reaction at the carboxyl carbon, which follows the general mechanism of Figure 6.5. Acid-catalyzed hydrolyses of carboxyhc esters that are derived from primary or from secondary alcohols take place according to the Aac2 mechanism. The reverse reactions of these hydrolyses follow the same mechanism, namely, the acid-catalyzed esterifications of carboxylic acids with alcohols. In the esterifications, the same intermediates are formed as during hydrolysis, but in the opposite order. 

Esterification.1 This reagent in combination with a catalytic amount of 4-dimethylaminopyridine (DMAP) is very effective for esterification of carboxylic acids with alcohols or thiols at room temperatures. However, reaction of aromatic and hindered acids requires several days at room temperature. French chemists report that only this method is useful for esterification of the protected baccatin III derivative (2) with (2R,3S)-N-benzoyl-0-(l-ethoxyethyl)-3-phenylisoserine (3) to provide the protected taxol derivative (4). A reaction conducted at 73° for 100 hours with 6 equiv. of 1 and 2 equiv. of DMAP produced 4 in 80% yield. Natural taxol, a cancer chemotherapeutic agent, is obtained by removal of the protective groups at C2 and C7 of 4. 

Predict the products of reactions of carboxylic acids with alcohols, amines, dia- Problems 20-35, 37, and 47... 

Carboxylic acids are protected as their esters such as methyl esters, tert-hutyl esters, allyl esters, benzyl esters, phenacyl esters and alkoxyalkyl esters. The esters are formed by the reaction of carboxylic acid with alcohol, and the reaction is known as esterification. 

The Mitsunobu esterification of carboxylic acids with alcohols in the presence of Ph3P and DEAD (diethyl azodicarboxylate) occurs under neutral conditions and provides the corresponding esters in high yields. 

ArsBi bearing ortho methoxy groups mediates dehydrative condensation of a-monosubstituted carboxylic acids with alcohols and amines (Scheme 14.139) [288]. Macrocyclic esters can be synthesized by the ArsBi-templated reaction of diols with dicarboxylic acid derivatives [289]. The Bi-C bonds of Ar Bi are cleaved by diphenyl diselenide and ditelluride to give aryl phenyl selenides and tellurides, respectively (Scheme 14.140) [290]. The reaction of ArsBi with elemental chalcogen (E Se, Te) affords a mixture of the respective dichalcogenides (ArEEAr) and monochalcogenides (ArEAr). 

Direct room temperature esterification of carboxylic acids with alcohols, including tert. alcohols with the help of dicyclohexylcarbodiimide (DCC) and 4-diakylaminopyridine catalysts 3. 

Esterification. Heating carboxylic acids with alcohols in toluene at 80° in the presence of Ph2NH20Tf (1 mol%) furnishes esters (12 examples, 78-96%). The same catalyst can be used in transesterification. Improved yields are obtained by adding McjSiCl as cocatalyst. 

To obtain rate equations for the esterification reactions (1) and (2), a detailed knowledge of the underlying mechanisms is necessary. For the acid-catalyzed esterification of carboxylic acids with alcohols, the mechanism was proposed (Figure 5.2). 

Figure 5.2. Acid-catalyzed esterification of carboxylic acids with alcohols.

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