Esters, active catalysis

Most nucleophiles are both more basic and more reactive towards sp -hybridized carbon than is water. Thus catalysis is readily observed wilh those esters which undergo hydrolysis at a significant rate in neutral solution, that is, with esters activated by electron withdrawing substituents in either the acyl or the leaving group. Hydroxide ion, however, is basic enough to attack any ester, and since the mechanism of alkaline hydrolysis appears to be relatively simple this reaction will be discussed first. 

The cinnamyl ester, which is somewhat more stable to nucleophiles, 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, 8h, 59-96% yield) or DMAP (CH3CN, heat). It is cleaved under nearly neutral conditions [Hg(OAc)2, MeOH, 23°C, 2-4 h KSCN, HjO, 23°C, 12-16 h, 90% yield] by treatment with sulfated Sn02, toluene, anisole, reflux or with K-10 clay and microwave heating. The latter conditions will also cleave crotyl and prenyl esters. Pd catalysis may also be used to induce cleavage either with a nucleophile or reductively with TEA/HC02H. ... 

Hersfield, R., Schmir, G. L. (1973). Hydrolysis of acyl-activated thiol esters, acid catalysis and acid inhibition, J. Am. Chem. Soc., 75 3994. 

By applying a new mode of cooperative catalysis involving the combination of a chiral Bronsted acid and a -symmetric biaryl saturated imidazolium precatalyst, Lee and Scheldt disclosed a highly enantioselective NHC-cata-lyzed [3 + 2] annulation reaction between a,p-alkynals and a-keto esters to generate the desired y-crotonolactones in high yields and excellent levels of enantioselectivity (up to 92% yield, 92% ee). The authors proposed that NHC-bound allenolate underwent addition to the a-keto ester activated by the chiral Bronsted acid derived co-catalyst (Scheme 7.43). 

Inspired by the many hydrolytically-active metallo enzymes encountered in nature, extensive studies have been performed on so-called metallo micelles. These investigations usually focus on mixed micelles of a common surfactant together with a special chelating surfactant that exhibits a high affinity for transition-metal ions. These aggregates can have remarkable catalytic effects on the hydrolysis of activated carboxylic acid esters, phosphate esters and amides. In these reactions the exact role of the metal ion is not clear and may vary from one system to another. However, there are strong indications that the major function of the metal ion is the coordination of hydroxide anion in the Stem region of the micelle where it is in the proximity of the micelle-bound substrate. The first report of catalysis of a hydrolysis reaction by me tall omi cell es stems from 1978. In the years that... 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

Until recently, the catalytic role of Asp ° in trypsin and the other serine proteases had been surmised on the basis of its proximity to His in structures obtained from X-ray diffraction studies, but it had never been demonstrated with certainty in physical or chemical studies. As can be seen in Figure 16.17, Asp ° is buried at the active site and is normally inaccessible to chemical modifying reagents. In 1987, however, Charles Craik, William Rutter, and their colleagues used site-directed mutagenesis (see Chapter 13) to prepare a mutant trypsin with an asparagine in place of Asp °. This mutant trypsin possessed a hydrolytic activity with ester substrates only 1/10,000 that of native trypsin, demonstrating that Asp ° is indeed essential for catalysis and that its ability to immobilize and orient His is crucial to the function of the catalytic triad. 

Poly(L-malate) decomposes spontaneously to L-ma-late by ester hydrolysis [2,4,5]. Hydrolytic degradation of the polymer sodium salt at pH 7.0 and 37°C results in a random cleavage of the polymer, the molecular mass decreasing by 50% after a period of 10 h [2]. The rate of hydrolysis is accelerated in acidic and alkaline solutions. This was first noted by changes in the activity of the polymer to inhibit DNA polymerase a of P. polycephalum [4]. The explanation of this phenomenon was that the degradation was slowest between pH 5-9 (Fig. 2) as would be expected if it were acid/base-catalyzed. In choosing a buffer, one should be aware of specific buffer catalysis. We found that the polymer was more stable in phosphate buffer than in Tris/HCl-buffer. 

The catalytic activity of surfactant micelles and the effect of the concentration of reagents in micelle catalysis are tested on hydrolysis of esters of phosphorus acids [25],... 

The mechanism for the lipase-catalyzed reaction of an acid derivative with a nucleophile (alcohol, amine, or thiol) is known as a serine hydrolase mechanism (Scheme 7.2). The active site of the enzyme is constituted by a catalytic triad (serine, aspartic, and histidine residues). The serine residue accepts the acyl group of the ester, leading to an acyl-enzyme activated intermediate. This acyl-enzyme intermediate reacts with the nucleophile, an amine or ammonia in this case, to yield the final amide product and leading to the free biocatalyst, which can enter again into the catalytic cycle. A histidine residue, activated by an aspartate side chain, is responsible for the proton transference necessary for the catalysis. Another important factor is that the oxyanion hole, formed by different residues, is able to stabilize the negatively charged oxygen present in both the transition state and the tetrahedral intermediate. 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

Ring-opening reactions with 3-alkylaziridine esters 36 take a similar course. The reactions are in practically all cases regio- and stereospecific with attack at C-3. An important difference is that the aziridine ring needs to be activated by an electron-withdrawing substituent, such as a tosyl or a benzyloxycarbonyl group. In addition, for benzenethiol, indole, and DMF, catalysis with BF3 was necessary (Scheme 22) [31]. 

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]. 

If k2 > kj, the glycosyl-enzyme intermediate will accumulate, and may be trapped by the rapid denaturation of the enzyme in the presence of (saturating) amounts of substrate. With -glucoside Aj from Asp. wentii and 4-nitrophenyl [ C]-2-deoxy-) -D-irra />jo-hexopyranoside, it was possible to identify the intermediate as a glycosyl ester (acylal) of 2-deoxy-D-arabino-hexose bound to the same aspartate residue that had previously been labeled with the active-site-directed inhibitor conduritol B epoxide and with D-glucal." This constituted an important proof that the carboxylate reacting with the epoxide is directly involved in catalysis. 

So far, various dicarboxylic acid derivatives, dicarboxylic acids, their activated and non-activated esters, cyclic acid anhydrides, and polyanhydrides have been polymerized with glycols through lipase catalysis to give polyesters. 

Shape selective catalysis as typically demonstrated by zeolites is of great interest from scientific as well as industrial viewpoint [17], However, the application of zeolites to organic reactions in a liquid-solid system is very limited, because of insufficient acid strength and slow diffusion of reactant molecules in small pores. We reported preliminarily that the microporous Cs salts of H3PW12O40 exhibit shape selectivity in a liquid-solid system [18]. Here we studied in more detail the acidity, micropore structure and catal3rtic activity of the Cs salts and wish to report that the acidic Cs salts exhibit efficient shape selective catalysis toward decomposition of esters, dehydration of alcohol, and alkylation of aromatic compound in liquid-solid system. The results were discussed in relation to the shape selective adsorption and the acidic properties. 

The second step, nucleophilic attack of an alcohol or phenol on the activated carboxylic acid RCOIm (carboxylic acid imidazolide), is usually slow (several hours), but it can be accelerated by heating[7] or by adding a base[8] [9] such as NaH, NaNH2, imidazole sodium (ImNa), NaOR, triethylamine, diazabicyclononene (DBN), diazabicycloimdecene (DBU), or /7-dimethylaminopyridine to the reaction mixture (see Tables 3—1 and 3—2). This causes the alcohol to become more nucleophilic. Sodium alcoholate applied in catalytic amounts accelerates the ester synthesis to such an extent that even at room temperature esterification is complete after a short time, usually within a few minutes.[7H9] This catalysis is a result of the fact that alcoholate reacts with the imidazolide very rapidly, forming the ester and imidazole sodium. 

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