Esters, carboxylic acid transesterification

The process of transesterification is an important way to prepare a large number of esters from more complex or more simple esters without passing through the carboxylic acid. Transesterification can be used to convert one type of ester to another type that can then be removed under a different set of conditions. This section describes many of the methods that have been found effective for ester metathesis. ... 

Without additional reagents /3-Diethylaminoethyl esters of thiazole carboxylic acids Transesterification... 

The cinnamyl ester can be prepared from an activated carboxylic acid derivative and cinnamyl alcohol or by transesterification with cinnamyl alcohol in the presence of the H-Beta Zeolite (toluene, reflux, 8 h, 59-96% yield). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°, 2-A h KSCN, H2O, 23°, 12-16 h, 90% yield]or by treatment with Sulfated-Sn02, toluene, anisole, reflux. The latter conditions also cleave crotyl and prenyl esters. 

Conversion of Free or Silylated Carboxylic Acids into Esters, Thioesters, Lactones, or Ketenes. Transesterification of Esters with Alcohols... 

One of the most important characteristics of IL is its wide temperature range for the liquid phase with no vapor pressure, so next we tested the lipase-catalyzed reaction under reduced pressure. It is known that usual methyl esters are not suitable for lipase-catalyzed transesterification as acyl donors because reverse reaction with produced methanol takes place. However, we can avoid such difficulty when the reaction is carried out under reduced pressure even if methyl esters are used as the acyl donor, because the produced methanol is removed immediately from the reaction mixture and thus the reaction equilibrium goes through to produce the desired product. To realize this idea, proper choice of the acyl donor ester was very important. The desired reaction was accomplished using methyl phenylth-ioacetate as acyl donor. Various methyl esters can also be used as acyl donor for these reactions methyl nonanoate was also recommended and efficient optical resolution was accomplished. Using our system, we demonstrated the completely recyclable use of lipase. The transesterification took place smoothly under reduced pressure at 10 Torr at 40°C when 0.5 equivalent of methyl phenylthioacetate was used as acyl donor, and we were able to obtain this compound in optically pure form. Five repetitions of this process showed no drop in the reaction rate (Fig. 4). Recently Kato reported nice additional examples of lipase-catalyzed reaction based on the same idea that CAL-B-catalyzed esterification or amidation of carboxylic acid was accomplished under reduced pressure conditions. ... 

Esterification and transesterification using TiIV compounds are useful methods for functionalization of ester moieties under mild conditions. In the transformation of carboxylic acids to esters, a catalytic amount of TiCl(OTf)3 is effective (Scheme 30).110 Titanium alkoxides, such as Ti(OEt)4 or Ti(0 Pr)4, easily promote transesterification of alkoxy groups to other ones—even to more hindered groups.111 Anomerization of glycosides to Q-isomers using a Tilv-bascd Lewis acid is an important method for controlling the product structure.112... 

Histidine residues are efficient nucleophiles in aqueous solution at pH 7, much more so than lysines, and this is the basis for the site-selective functionalization of lysine residues in folded polypeptides and proteins [24, 25]. p-Nitrophenyl esters react with His residues in a two-step reaction to form an acyl intermediate under the release of p-nitrophenol followed by the reaction of the intermediate with the most potent nucleophile in solution to form the reaction product. In aqueous solution the reaction product is the carboxylic acid since the hydroxide ion is the most efficient nucleophile at pH 7. If there is an alcohol present the reaction product will be an ester and the overall reaction is a transesterification reaction. 

Vinyl acetate was produced by the catalytic acetylation of acetylene, but this monomer is now produced by the catalytic oxidative condensation of acetic acid and ethylene (structure 17.32). Other vinyl esters can be produced by the transesterification of vinyl acetate with higher boiling carboxylic acids. 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

Naturally occurring fatty alcohols used in the fragrance industry are produced principally by reduction of the methyl esters of the corresponding carboxylic acids, which are obtained by transesterification of natural fats and oils with methanol. Industrial reduction processes include catalytic hydrogenation in the presence of copper-chromium oxide catalysts (Adkins catalysts) and reduction with sodium (Bouveault—Blanc reduction). Unsaturated alcohols can also be prepared by the latter method. Numerous alcohols used in flavor compositions are, meantime, produced by biotechnological processes [11]. Alcohols are starting materials for aldehydes and esters. 

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). 

Esters are less reactive than acid chlorides and acid anhydrides. They are converted to carboxylic acid hy acid or base hydrolysis, and to another ester by acid or base alcoholysis (transesterification). The 1°, 2° or 3° amides are obtained from esters by treatment with ammonia or 1° or 2° amines, respectively. 

Alcoholysis of trihalides 0-6 Hydrolysis of ortho esters 0-20 Alcoholysis of acyl halides 0-21 Alcoholysis of anhydrides 0-22 Esterification of carboxylic acids 0-23 Transesterification 0-24 Alkylation of carboxylic acid salts 0-25 Cleavage of ethers with anhydrides 0-26 Alkylation of carboxylic acids with diazo compounds... 

Dealkoxycarbonylation This reaction can be conducted by heating a ma-lonic or (3-keto ester at 200° in the presence of a catalytic amount of this phos-phonium salt and a high molecular weight carboxylic acid such as stearic acid as the solvent and proton source. The reaction involves catalyzed transesterification followed by decarboxylation. Yields are typically 70-90%. 

The catalytic action of ChE s is, however, not limited to ester hydrolysis. Thus, these enzymes catalyze also the reverse reaction, i.e., esterification of acids with choline (14). They promote transesterification 15) and the condensation of hydroxylamine with acids 14) or esters 15). Anhydrides of carboxylic acids are also substrates of ChE s 16, 17) and can undergo all the reactions, mentioned with esters, i.e., hydrolysis, esterification, and hydroxamation. 

Alternative reactions employ coupling reagents such as DCC (Steglich Esterification), preformed esters (transesterification), carboxylic acid chlorides or anhydrides. These reactions avoid the production of water. Another pathway for the production of esters is the formation of a carboxylate anion, which then reacts as a nucleophile with an electrophile (similar reactions can be found here). Esters may also be produced by oxidations, namely by the Baeyer-Villiger oxidation and oxidative esterifications. 

Miyazawa, T. Kurita, S. Shimaoka, M. Ueji, S. Yamada, T. Resolution of racemic carboxylic acids via the lipase-catalyzed irreversible transesterification of vinyl esters. Chirality 1999, 11 554-560. 

If the alcoholate or the alkylating reagent contains a carboxylic acid ester, acylation of the alcoholate can compete with alkylation. This potential side reaction does not cause trouble in the examples sketched in Scheme 6.14 (first and third reactions), because these esters are sterically hindered and devoid of a hydrogen (no ketene formation can occur) but, as illustrated in Scheme 6.15, less hindered esters can readily undergo transesterification with alcoholates. 

Carboxylic acids with strongly electron-withdrawing groups, for example trifluoro-acetic or 2,4,6-trinitrobenzoic acid [22], are readily converted into esters or amides. The products can, however, be unusually sensitive toward attack by nucleophiles and can readily undergo hydrolysis, transesterification, or transamidation. 2,4,6-Tris(trifluoromethyl)benzoic acid has been reported to undergo conversion into the acyl chloride or esters only with difficulty [23]. 

Acyl iodides.1 This reagent converts acyl chlorides into acyl iodides at 25°. In combination with iodine (1 1) it also converts carboxylic acids, esters, and anhydrides into acyl iodides in generally high yield. This reaction in combination with an alcohol is a useful method for transesterification of hindered alcohols. 

Problem-Solving Strategy Proposing Reaction Mechanisms 1007 Mechanism 21-8 Transesterification 1008 21-7 Hydrolysis of Carboxylic Acid Derivatives 1009 Mechanism 21-9 Saponification of an Ester 1010 Mechanism 21-10 Basic Hydrolysis of an Amide 1012 Mechanism 21-11 Acidic Hydrolysis of an Amide 1012 Mechanism 21-12 Base-Catalyzed Hydrolysis of a Nitrile 1014 21-8 Reduction of Acid Derivatives 1014... 

Figure 5.21. Reaction schemes for the most common types of step-growth polymerization. Shown are (a/c) polyester formation, (b/d) polyamide formation, (e) polyamide formation through reaction of an acid chloride with a diamine, (f) transesterification involving a carboxylic acid ester and an alcohol, (g) polybenzimidazole formation through condensation of a dicarboxyhc add and aromatic tetramines, and (h) polyimide formation from the reaction of dianhydrides and diamines.

The hydroboration of acetylenes (3) with diisopinocampheylborane (IpC)2BH in THF led after refunctionalisation and transesterification to the olefins (4a, b, c) isolated in good yields. Monooxidation with mCpBA led to the sulfoxide (4d) whereas the sulfone (4e) was obtained with two equivalents of mCpBA. The same sulfone (4e) could also be obtained in an excellent overall yield by radical addition of phenylsulfonyl iodide to the pinacol ester of vinylboronic acid followed by a dehydroiodination in the presence of Et2N (87 % overall yield). The carboxylic ester (4a) could be transformed into the corresponding carboxylic acid (4f) (79 % yield) 11 which led to the acid chloride (4g) by treatment with freshly distilled thionyl chloride at 0°C (91 % yield), p-keto vinylboronates are easily accessible by oxidation of the corresponding protected allylic alcohol according to the following scheme ... 

Removal of the chiral auxiliary is easily achieved by hydrolysis with lithium hydroxide or transesterification with titanium tetrabenzyloxide [Ti(OBn)J affording the carboxylic acids 8 (esters 9) and recovered oxazolidinone 10. 

Under almost anhydrous conditions in organic medium, lipases can be used in the reverse mode for direct ester synthesis from carboxylic acids and alcohols, as well as transesterifications (acyl transfer reactions) which can be divided into alcoholysis (ester and alcohol), acidolysis (ester and acid), and interesterification (ester-ester interchange). The direct esterification and alcoholysis in particular have been most frequently used in asymmetric transformations involving lipases. The parameters that influence enzymatic catalysis in organic solvents have been intensively studied and discussed. ... 

Enantiomerically pure carboxylic acids are routinely obtained from N-acylsultams by Hydrogen Peroxide assisted saponification with Lithium Hydroxide in aqueous THF. 4 Alternatively, transesterification can be effected under neutral conditions in allyl alcohol containing Titanium Tetraisopropoxide, giving the corresponding allyl esters which can be isomerized/hydrolyzed with Wilkinson s catalyst (Chlorotris(triphenylphosphine)rhodium(I)) in Et0H-H20. This provides a convenient route to carboxylic acids containing base-sensitive functionality. Primary alcohols are obtained by treatment with L-Selectride (Lithium Tri-s-butylborohydride) in THF at ambient temperature. ... 

Titanium alkoxide is quite effective, presumably as an acid/base catalyst, at facilitating transesterification between esters and alcohols [511-513]. The reaction conditions are mild and relatively hindered alcohols can be used. Methyl phenylacetate has been transformed to other esters of relatively hindered alcohols under the influence of Ti(OEt)4 (Eq. 216) [514]. Ethyl (or methyl) esters of a variety of functionalized carboxylic acids could be converted into menthyl esters in good yields under titanium catalysis (Eq. 217) [514]. 

In a related approach, pentafluorophenyl esters of Fmoc amino acids 61 (see Table 14) were prepared from a mixture of acid 59 and pentafluorophenyl trifluoroacetate in dimeth-ylformamide in the presence of pyridine,which is a transesterification method developed by Sakakibara (Scheme The reaction involves formation of mixed carboxylic acid... 

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