Carboxylic transesterification

A major drawback of the carboxylation/transesterification of ethylene oxide is the co-production of ethylene glycol. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

Regioselective Acylation of Hydroxy Compounds. AUphatic diols can be selectively acylated at the primary position by a number of Upases in nonaqueous solvents. For example, PPL suspended in solutions of various diols in ethyl carboxylates catalyzes transesterification in a highly regioselective manner, producing primary monoesters in up to 97% yield (93). Similarly, chloramphenicol [56-75-7] (72) (R = NO2) can be acylated by a number of Upases to produce optically pure, water-insoluble 3-0-palmitate in a highly selective manner (94). 

In an attempt to prepare an isothiazolobenzodiazepine, ethyl 5-o-aminoanilino-3-methyl-isothiazole-4-carboxylate was treated with sodium methoxide, but the only reaction was transesterification to the methyl ester 76UC(B)394). Only the 5-ester group of dimethyl 3-methylisothiazole-4,5-dicarboxylate reacts with iV,iV -diphenylguanidine, as with the corresponding isoxazole compound, but the product could not be cyclized, even under drastic conditions. This is in marked constrast to the isoxazole compound which cyclized at room temperature (80JCS(P1)1667). 

The Dim ester was developed for the protection of the carboxyl function during peptide synthesis. It is prepared by transesterification of amino acid methyl esters with 2-(hydroxymethyl)-l,3-dithiane and Al(/-PrO)3 (reflux, 4 h, 75°, 12 torr, 75% yield). It is removed by oxidation [H2O2, (NH4)2Mo04 pH 8, H2O, 60 min, 83% yield]. Since it must be removed by oxidation it is not compatible with.sulfur-containing amino acids such as cysteine and methionine. Its suitability for other, easily oxidized amino acids (e.g., tyrosine and tryptophan) must also be questioned. It is stable to CF3CO2H and HCl/ether. - ... 

Chirazymes. These are commercially available enzymes e.g. lipases, esterases, that can be used for the preparation of a variety of optically active carboxylic acids, alcohols and amines. They can cause regio and stereospecific hydrolysis and do not require cofactors. Some can be used also for esterification or transesterification in neat organic solvents. The proteases, amidases and oxidases are obtained from bacteria or fungi, whereas esterases are from pig liver and thermophilic bacteria. For preparative work the enzymes are covalently bound to a carrier and do not therefore contaminate the reaction products. Chirazymes are available form Roche Molecular Biochemicals and are used without further purification. 

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. ... 

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. 

Subsequently it was found140 that ethyl 2-alkyl-1//-azepine-1-carboxylates can be isolated from a mixture of isomeric 1//-azepines by stirring the mixture with potassium hydroxide in ethanol at room temperature. Apparently, this method, which is limited to 2-alkylated azepines, depends on the slower rate of hydrolysis (and subsequent decomposition of the resulting 1H-azepine-l-carboxylic acid) of the sterically hindered 1-(ethoxycarbonyl) group. Although the yields of l//-azepines are poor (4-7%, vide supra), the method provides access to otherwise difficult to obtain, isomerically pure 2-alkyl-1//-azepines. Under the basic hydrolysis conditions aryl 2-alkyl-l//-azepine-1-carboxylates undergo transesterification to the l-(ethoxycarbonyl) derivatives. 

PET is the polyester of terephthalic acid and ethylene glycol. Polyesters are prepared by either direct esterification or transesterification reactions. In the direct esterification process, terephthalic acid is reacted with ethylene glycol to produce PET and water as a by-product. Transesterification involves the reaction of dimethyl terephthalate (DMT) with ethylene glycol in the presence of a catalyst (usually a metal carboxylate) to form bis(hydroxyethyl)terephthalate (BHET) and methyl alcohol as a by-product. In the second step of transesterification, BHET... 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

Transesterification and Hydrolysis of Carboxylic Acid Derivatives, Alcohols, and Epoxides... 

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

Besides allylic substitution reactions it was also shown that [Fe(CO)3(NO)] 76 is catalytically active in transesterification reactions under neutral conditions (Scheme 24) [70]. Various activated acyl donors 97 can be used to give rise to the corresponding carboxylic esters 100 in good to excellent yields. This reaction proceeds in the absence of additional ligands in nonpolar solvents, for example, hexane. Mechanistically, the reaction is assumed to proceed via a Fe-acyl-complex 98 (Scheme 24). 

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. ... 

Early studies using calcium oxide, carbonate, and carboxylates reported low activities for the polymerization of LA, even in bulk at 120-180 °C.827,828 PolyGA and copolymers of GA with CL and L-LA have been prepared using Ca(acac)2, but again high temperatures (150-200 °C) are required.829 Under these conditions transesterification occurs, although to a lesser extent than in analogous Sn(Oct)2-initiated polymerizations. 

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... 

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