Carboxylic acids, esterification reactions with alcohols

The combination of carboxyl activation by a carbodiimide and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols.10 The reaction proceeds at room temperature. Carbodiimides are widely applied in the synthesis of polypeptides from amino acids. The proposed mechanism for this esterification reaction involves activation of the acid via isourea 28 followed by reaction with another acid molecule to form anhydride... 

FIGURE 3.18 Protection of carboxyl groups by esterification of amino acids (A) by acid-catalyzed reaction with alcohol. [Curtius 1888, Fisher 1906] with X = Cl for H-Xaa-OMe, X-Xaa-OEt, and H-Pro-OCH2Ph ... 

The formation of ketene intermediates facilitates the carbodiimide mediated esterification reaction with alcohols and phenols when carboxylic acids with an electron withdrawing group in the a-position are used as substrates. ... 

Esters can be prepared by acid-catalyzed esterification or by reaction of the acid chloride with the alcohol. In small-scale syntheses, it is often more convenient to prepare the ester by reaction of the carboxylic acid with the appropriate diazo compound. Diazomethane is routinely used for making methyl esters, but more highly substituted esters can be prepared if the corresponding diazo compound is available. Benzhydryl esters, for example, are readily prepared from carboxylic acids by reaction with diphenyldiazomethane ... 

Highly concentrated ether carboxylic acids with a low degree of ethoxylation even at room temperature can give an esterification reaction with the non-converted nonionic, especially with the fatty alcohol, to several percentage points. The result may be that a too low value is found for the ether carboxylate content. This mistake in analysis can be avoided by saponification of the formed ester [238]. Two hundred to 300 mg matter and ca 100 mg NaOH were weighed in a 50-ml Erlenmeyer glass, heated with 20 ml ethanol under reflux, and after cooling supplied with water to 100 ml. Afterward a two-phase titration was carried out. 

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. 

Esterification is generally carried out by refluxing the reaction mixture until the carboxylic acid has reacted with the alcohol and the water has been split off. The water of the ester is removed from the equilibrium by-distillation. The choice of the esterification process to obtain a maximum yield is dependent on many factors, i.e.. no single process has universal applicability. 

Here, we report the application of this procedure for immobilizing Mucor miehei lipase. A catalytic test was aimed at producing esters by direct esterification reactions with a large range of carboxylic acids (from C4 to C16), and a diversity of alcohols (from C4 to C8). Several reaction model systems are analyzed in order to illustrate the kind of products that can be made by using an experimental preparation of lipase immobilized on POS-PVA particles. 

Although the previous two sections of this chapter emphasized hydrolytic processes, two mechanism that led to O or N-acylation were considered. In the discussion of acid-catalyzed ester hydrolysis, it was pointed out that this reaction is reversible (p. 654). Thus it is possible to acylate alcohols by acid-catalyzed reaction with a carboxylic acid. This is called the Fischer esterification method. To drive the reaction forward, the alcohol is usually used in large excess, and it may also be necessary to remove water as it is formed. This can be done by azeotropic distillation in some cases. 

This alcoholysis of carboxylic esters under the influence of alkaline catalysts is important for the preparation of esters of long-chain alcohols with heat-sensitive carboxylic acids, e.g., with /ff-keto carboxylic acids,858-864 and of esters of acid-sensitive alcohols860-863 that cannot be subjected to the usual methods of esterification. For such reactions sodium alkoxides,853 sodium hydroxide,854 855 and potassium carbonate856 have proved useful as catalysts. 

Esterification. Carboxylic acids react with (1) in CHCI3 or acetonitrile in the presence of 1 eq. of triethylamine to form an active ester (2), which can be isolated if desired. The esters (2) react with an alcohol, again in the presence of 1 eq. of base, to form an ester of the carboxylic acid. The reaction can be carried out in one step by mixing the acid, the alcohol, the coupling reagent, and 2 eq. of base in ether. In either case, the reaction takes place at 20°. Yields are generally in the range of 65-85%. 

As a result of their large polarity, the surfaces of inorganic filler always adsorb hydroxyl or water molecules, which can be subjected to an esterification reaction with the carboxyl of fatty acids or alcohol carboxyl. Consequently, an organic layer is introduced on the surface of inorganic particles. Therefore, the surface energy of the inorganic filler decreases and the hydrophobicity increases. For example, calcium carbonate was treated by stearic acid. The chemical reactions on the surface of calcium carbonate are shown in Figure 2.3. " ... 

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

Ammonium hexanitratocerate(IV) is an efficient catalyst for fast esterification of carboxylic acids and alcohols under mild conditions (Goswami and Chowdhury, 2000). The reaction can be carried out under solventless conditions, or in chloroform. The reaction works with primary and secondary alcohols, and with aliphatic carboxylic acids. No reaction was observed for tertiary alcohols or for aromatic acids. The method is of interest because it is also applicable to the esterification of alcohols based on steroids and on other natural products (scheme 37). Pan and coworkers described the esterification of phenylacetic acids and cis-o cic acid with simple primary and secondary alcohols in presence of an excess of CAN at room temperature (Pan et al., 2003). The alcohol acted as solvent. Ammonium hexanitratocerate(IV) does catalyze not only the esterification of carboxylic acid, but also the transesterification with another alcohol (Stefane et al., 2002). 

One of the first examples of the grafting to approach was published by Sun et al. in 2001 [32]. In this work carboxylic acid groups on the nanotube surface were converted into acyl chlorides by refluxing the samples in thionyl chloride. Then the acid chloride functionalized carbon nanotubes were reacted with hydroxyl groups of dendritic PEG polymers via esterification reactions. Similarly, many polymers terminated with amino or hydroxyl moieties have been used in amidation and esterification reactions with acid chloride modified NTs poly(propionylethylenimine-co-ethylenimine) (PPEI-EI) [33], poly(styrene-co-aminomethylstyrene) (PSN) [34], poly-(amic acid) containing bithiazole rings [35], monoamine-terminated poly(ethylene oxide) (PEO) [36], poly(styrene-co-hydroxymethylstyrene) (PSA) [37], poly(styrene-co-p-[4-(4 -vinylphenyl)-3-oxabutanol]) (PSV) [38], poly(vinyl alcohol) (PVA) [39], poly(vinyl acetate-co-vinyl alcohol) (PVA-VA) [40] or poly[3-(2-hydroxyethyl)-2,5-thienylene] (PHET) [41]. 

Oxidation of the primary alcohol gives the corresponding carboxylic acid (A). Reaction of A with thionyl chloride converts the carboxylic acid to the acid chloride (B). Reaction of B with excess ammonia produces the amide (C). Carboxylic acid (A) undergoes Fischer esterification upon reaction with ethanol and catalytic acid to produce the ethyl ester (D). Reaction of acid chloride B with a lithium trialkoxyalumimrm hydride produces aldehyde F, which can also be made from ester D by reaction with DIBAH (E). 

Now let s draw the forward scheme. The starting alcohol is oxidized upon treatment with chromic acid (alternatively, PCC can be used for this step). The resulting ketone is then treated with molecular bromine (Br2) and sodium hydroxide, followed by aqueous acid, to give a carboxylic acid (via a haloform reaction). Finally, the carboxylic acid is treated with ethanol in the presence of an acid catalyst, giving the desired ester (via a Fischer esterification). 

Although the term ester used without a modifier is normally taken to mean an ester of a carboxylic acid alcohols can react with inorganic acids m a process similar to the Fis cher esterification The products are esters of inorganic acids For example alkyl nitrates are esters formed by the reaction of alcohols with nitric acid... 

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