Carboxylic acids fischer

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 (equation 10) Owing to the strong acidity of a fluorinated carboxylic acids, Fischer esten-ficaiton with most aliphatic alcohols proceeds autocatalytically [79 20]... 

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. 

Depsides and Tannins. In forming depsides (poljnmers of phenol carboxylic adds) and tannin (sugar esters of phenol carboxylic acids), Fischer prepared the alkyl carbonates of the phenol carboxylic acids. Treatment of these products with phosphorus pentachloride gave the corresponding acid chlorides the latter were useful in preparing depsides and tannins. Using such reagente. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

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... 

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... 

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... 

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... 

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

The first indolization of an arylhydrazone was reported in 1983 by Fischer and Jourdan" by treatment of pyruvic acid 1-methylphenylhydrazone 3 with alcoholic hydrogen chloride. However, it was not until the following year that Fischer and Hess identified the product from this reaction as 1-methyl indole-2-carboxylic acid 4. 

Fischer indolization of 9-arylhydrazono-6,7,8,9-tetrahydro-4//-pyrido-[l,2-u]pyrimidin-4-ones 289 by heating in 85% phosphoric acid, or in PPA yielded 7,12-dihydropyrimido[l, 2 l,2]pyrido[3,4-Z)]indol-4(6//)-ones 290 (96JHC799, 99MI12, 00MI22). From the 3-ester and 3-carboxylic acid derivatives 289 (R = COOEt, COOH) and decarboxylated products 290 (R = H) were obtained. 

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. 

Mechanism of Fischer esterification. The reaction is an acid-catalyzed, nucleophilic acyl substitution of a carboxylic acid. 

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 s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

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

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. 

Interestingly, the Fischer indole synthesis does not easily proceed from acetaldehyde to afford indole. Usually, indole-2-carboxylic acid is prepared from phenylhydrazine with a pyruvate ester followed by hydrolysis. Traditional methods for decarboxylation of indole-2-carboxylic acid to form indole are not environmentally benign. They include pyrolysis or heating with copper-bronze powder, copper(I) chloride, copper chromite, copper acetate or copper(II) oxide, in for example, heat-transfer oils, glycerol, quinoline or 2-benzylpyridine. Decomposition of the product during lengthy thermolysis or purification affects the yields. 

The first commercial Fischer-Tropsch facility was commissioned in 1935, and by the end of the Second World War a total of fourteen plants had been constructed. Of these, nine were in Germany, one in France, three in Japan, and one in China. Both German normal-pressure and medium-pressure processes (Table 18.1) were employed. The cobalt-based low-temperature Fischer-Tropsch (Co-LTFT) syncrude produced in these two processes differed slightly (Table 18.2), with the product from the medium-pressure process being heavier and less olefinic.11 In addition to the hydrocarbon product, the syncrude also contained oxygenates, mostly alcohols and carboxylic acids. 

The refinery design had to make provision for dealing with the oxygenates present in the syncrude. The beneficial use of alcohols has been noted. Carboxylic acids were neutralized and the resulting soaps recovered. However, the Fischer-Tropsch aqueous product was not refined. 

The refinery design included the recovery of nonacid oxygenates in the Fischer-Tropsch aqueous product that are lighter boiling than water.30 The oxygenate chemicals recovered from the aqueous product included methanol (mainly from Fe-LTFT), ethanol (from Fe-HTFT, Fe-LTFT, and acetaldehyde hydrogenation), as well as mixed heavier alcohol and ketone streams. The carboxylic acids were not recovered and were processed with the wastewater. 

The Fischer-Tropsch synthesis, which may be broadly defined as the reductive polymerization of carbon monoxide, can be schematically represented as shown in Eq. (1). The CHO products in Eq. (1) are any organic molecules containing carbon, hydrogen, and oxygen which are stable under the reaction conditions employed in the synthesis. With most heterogeneous catalysts the primary products of the reaction are straight-chain alkanes, while the secondary products include branched-chain hydrocarbons, alkenes, alcohols, aldehydes, and carboxylic acids. The distribution of the various products depends on both the type of catalyst and the reaction conditions employed (4). 

Current interest in synthetic fuels production by Fischer-Tropsch (FT) reactions have created a need for removal of byproduct oxygenates, formed by the FT reaction. The oxygenates consist of primary and internal alcohols, aldehydes, ketones, esters and carboxylic acids. The hydrocarbon products derived from the FT reaction range from methane to high molecular weight paraffin waxes containing more than 50 carbon atoms. 

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. 

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