Formation of carboxylic esters

Lipases are the enzymes for which a number of examples of a promiscuous activity have been reported. Thus, in addition to their original activity comprising hydrolysis of lipids and, generally, catalysis of the hydrolysis or formation of carboxylic esters [107], lipases have been found to catalyze not only the carbon-nitrogen bond hydrolysis/formation (in this case, acting as proteases) but also the carbon-carbon bond-forming reactions. The first example of a lipase-catalyzed Michael addition to 2-(trifluoromethyl)propenoic acid was described as early as in 1986 [108]. Michael addition of secondary amines to acrylonitrile is up to 100-fold faster in the presence of various preparations of the hpase from Candida antariica (CAL-B) than in the absence of a biocatalyst (Scheme 5.20) [109]. 

The wide range of standard procedures that are available for the formation of carboxylic esters of primary and secondary alcohols in the presence of suitable acid catalysts is discussed in detail in Section 5.12.3, p. 695. Also included is the mild method for methyl ester formation from the carboxylic acid and diazomethane, and a method appropriate for sterically hindered esters involving the acid, a secondary or tertiary alkyl halide, and the non-nucleophilic base DBU (Expt 5.151). An example of the formation of a t-butyl ester is noted in Expt 6.165. 

Transformations of individual substituents include the formation of carboxylic esters and anhydrides (62BCJ808, 62YZ414 63CPB1431) as well... 

The results for the two reactions are quite close, and the known formation of carboxylate esters with incompletely equilibrated oxygens in the rearrangement of N-nitrosoamides (White and Aufdermarsh, 1961b) suggests that the small discrepancy may be due to the fact that the rate of equilibration provides too low a measure of the fraction of... 

The selective formation of carboxylic esters from aldehydes and alcohols in the presence of a hydrogen acceptor such as diphenylacetylene is catalyzed by Ru3(CO)12. For instance, benzyl benzoate is obtained from ben-zaldehyde and benzyl alcohol in 72% yield (CT 54) after 2 hr, when the reaction is carried out without solvent at 147°C (403) ... 

In the formation of carboxylic esters in an anhydrous organic solvent, its hydrophobicity and the water activity have a major influence on the reaction [30, 36, 134l Hence, the organic solvent used can significantly influence the selectivity of a lipase-catalyzed enantiotopos- or enantiomer-differentiating reaction. Furthermore, the acyl donor may influence reactivity and selectivity. 

On the other hand, when the Arbuzov reactions of aroyl (/ -nitrobenzoyl, benzoyl, p-chlorobenzoyl or / -toluoyl) chlorides were carried out in the presence of proton sources (i.e. excess of a carboxylic acid), phosphate phosphonates were obtained as shown in equation 19 The formation of these resulted from protonation of the initially formed carbanion, to form a phosphonate trialkoxyphosphonium ion, followed by nucleophilic dealkylation of the trialkoxyphosphonium moiety. Indeed, the formation of carboxylate esters as additional products was noted in these reactions. The type of products shown in this reaction show characteristic resonances in the NMR spectrum in the ranges 0.8-1.25 and 16-17 ppm with /pp = 29 Hz. Analogous results were observed in the reaction of 2-pyridoyl chloride with triethyl phosphite. ... 

Treatment of diazo compounds with an excess of nickel carbonyl in ethanol leads to the formation of carboxylic esters (64). 

Matsumoto and Mochida [33], using NMR with a hydrogenated coal tar pitch mesophase carbon fiber, showed that the initial attack by oxygen was on -CH3 and -CH2- groups, with the gradual formation of carboxyls, esters and aryl carbonyls. Fairly stable cross-links were formed via phenols, ethers and esters. The workers also found that slower heating rates (0.5°C/min instead of 2.0°C/min) produced better mechanical properties and that the final choice would be controlled by the desired target properties and economics. 

These reactions are carried out in aqueous/organic two-phase solvent systems with one of the reagents in an alkali metal salt form. Some examples of the anionic nucleophilic reagents (Y) are hydroxides, halides, cyanides, sulfides, cyanamides, carboxylates, sulfonates, and so forth. In fact, one of the most studied PEG phase transfer catalyzed reaction is the formation of carboxylate esters, such as acetates [159,1601. 

Formation of Carboxylic Esters and Ketones, Grignard reagents can also be converted into esters and ketones by Fe(CO)5 (to supply CO). A cathodic ester synthesis from alcohols and alkyl halides uses carbon monoxide (at 1 atm) and Fe(CO)s as a catalyst. ... 

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Ba.sic Hydrolysis. Throughout most of history, soap was manufactured by boiling an ester with aqueous alkaU. In this reaction, known as saponification, the ester is hydroly2ed with a stoichiometric amount of alkaU. The irreversible formation of carboxylate anion drives the reaction to completion. 

First, the acid anhydride is produced by the reaction of the free acid with DCC. NucleophiUc attack by 4-pyrroUdinonepyridine on the anhydride results in the corresponding, highly reactive acylpyridinium carboxylate this leads to the formation of cellulose ester, plus a carboxylate anion. The latter imdergoes a DCC-mediated condensation with a fresh molecule of acid to produce another molecule of anhydride. N,N-carbonyldiimidazole (CDl) may substitute DCC for acid activation, the intermediate being N-acyhmidazol,... 

Modifications at the carboxyl group include reduction (with dibor-ane260 or borohydride, after activation with soluble carbodiimide261,262), esterification (with diazomethane,101,223,283,264 or acyl or aryl chlorides224,264), and formation of amide esters.263,265... 

B Castro, J-R Dormoy, G Evin, C Selve. Peptide coupling reagents. Part VII. Mechanism of the formation of active esters of hydroxybenzotriazole in the reaction of carboxylate ions on the BOP reagent for peptide coupling. A comparison with Itoh s reagent. J Chem Res (S) 82, 1977. 

In spite of the general lack of detailed understanding of mechanism, the procedure is superior to that using the cobalt catalyst both in the overall yields and in the specificity of the reaction to produce only mono-carbonylation products. Prolonged reaction times may lead, however, to the formation of benzyl esters of the acids, as a result of a catalysed reaction of the halide with the carboxylate anion. 

Chloro-4,6-dimethoxy-l,3,5-triazine (100) reacts with iV-methylmorpholine at 20 °C to yield an isolable quaternary triazinylammonium salt (101 R = Me, R, R = C4H8O). This salt can then be reacted with a carboxylic acid to yield a 2-acyloxy-4,6-dimethoxy-l,3,5-triazine (102), which, in turn, can be reacted with an amine to yield an amide (103). This sequence of reactions provides an explanation for the activation (formation of reactive ester) of the carboxylic acid function by 2-chloro-4,6-disubstituted-l,3,5-triazines (100) in the presence of hindered amines. Several other hindered amines may replace iV-methylmorpholine in the process, but unhindered amines such as triethylamine and tributylamine were inactive. ... 

All tRNA molecules have the sequence -CCA at the 3 end. This three base sequence is termed the acceptor stem. The aminoacyl-tRNA synthetases catalyze the formation of an ester between the carboxyl group of the amino acid and the 3 -OH of the ribose of the terminal adenosine moiety ... 

Aluminum porphyrins with alkoxide, carboxylate, or enolate can also activate CO2, some catalytically. For example, Al(TPP)OMe (prepared from Al(TPP)Et with methanol) can bring about the catalytic formation of cyclic carbonate or polycarbonate from CO2 and epoxide [Eq. (6)], ° - and Al(TPP)OAc catalyzes the formation of carbamic esters from CO2, dialkylamines, and epoxide. Neither of the reactions requires activation by visible light, in contrast to the reactions involving the alkylaluminum precursors. Another key difference is that the ethyl group in Al(TPP)Et remains in the propionate product after CO2 insertion, whereas the methoxide or acetate precursors in the other reactions do not, indicating that quite different mechanisms are possibly operating in these processes. Most of this chemistry has been followed via spectroscopic (IR and H NMR) observation of the aluminum porphyrin species, and by organic product analysis, and relatively little is known about the details of the CO2 activation steps. 

Sulfuric acid can form ester derivatives with alcohols, though since it is a dibasic acid (pAla — 3, 2) it can form both mono- and di-esters. Thus, acid-catalysed reaction of methanol with sulfuric acid gives initially methyl hydrogen sulfate, and with a second mole of alcohol the diester dimethyl sulfate. Though not shown here, the mechanism will be analogous to the acid-catalysed formation of carboxylic acid esters (see Section 7.9). 

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