Selective reaction esterification

Resolution of racemic alcohols by acylation (Table 6) is as popular as that by hydrolysis. Because of the simplicity of reactions ia nonaqueous media, acylation routes are often preferred. As ia hydrolytic reactions, selectivity of esterification may depend on the stmcture of the acylatiag agent. Whereas Candida glindracea Upase-catalyzed acylation of racemic-cx-methylhenzyl alcohol [98-85-1] (59) with butyric acid has an enantiomeric value E of 20, acylation with dodecanoic acid increases the E value to 46 (16). Not only acids but also anhydrides are used as acylatiag agents. Pseudomonasfl. Upase (PFL), for example, catalyzed acylation of a-phenethanol [98-85-1] (59) with acetic anhydride ia 42% yield and 92% selectivity (74). 

Four different amino acids have been selected for esterification to study the effect of R-group substituent of amino acid on rate and ease of esterification. The four acids are alanine, serine, aspartic acid and lysine. Their respective esters were prepared by reported methods to authenticate and compare with those prepared by our method. Alanine was esterified with ethanol to yield the ethyl ester, keeping -NH3+ group intact. This was also confirmed by acidity of final reaction mixture (pH- 3.2). There was about 50% conversion of alanine to its ethyl ester. Further work on ester formation, including qualitative and quantitative analysis, is in process. 

In a faster, selective and cleaner applications of the microwave-accelerated reactions, Stone-Elander et al. have synthesized a variety of radiolabeled (with 3H, 11C, and 19F) organic compounds via the nucleophilic aromatic and aliphatic substitution reactions, esterifications, condensations, hydrolysis and complexation reactions using monomodal MW cavities on microscale [121]. A substantially reduced level of radioactive waste is generated in these procedures that are discussed, at length, in Chapt. 13 [122]. 

Regioselective esterification and acetylation reactions of lactose were described by Thelwall (1982). These selective reactions produced partially protected derivatives which were of value in the further modifica-... 

Enzymes are biocatalysts constructed of a folded chain of amino acids. They may be used under mild conditions for specific and selective reactions. While many enzymes have been found to be catalytically active in both aqueous and organic solutions, it was not until quite recently that enzymes were used to catalyze reactions in carbon dioxide when Randolph et al. (1985) performed the enzyme-catalyzed hydrolysis of disodium p-nitrophenol using alkaline phosphatase and Hammond et al. (1985) used polyphenol oxidase to catalyze the oxidation of p-cresol and p-chlorophenol. Since that time, more than 80 papers have been published concerning reactions in this medium. Enzymes can be 10-15 times more active in carbon dioxide than in organic solvents (Mori and Okahata, 1998). Reactions include hydrolysis, esterification, transesterification, and oxidation. Reactor configurations for these reactions were batch, semibatch, and continuous. 

Functionalisation of the polymer backbone through reaction of the hydroxyl groups (esterification and etherification), nucleophilic displacement reactions, oxidation and selective reactions at the terminal reducing ends... 

Finally, an elegant example of a product derived from renewable raw materials is the bioemulsifier, marketed by Mitsubishi, which consists of a mixture of sucrose fatty acid esters. The product is prepared from two renewable raw materials - sucrose and a fatty acid - and is biodegradable. In the current process the reaction is catalysed by a mineral acid, which leads to a rather complex mixture of mono- and di-esters. Hence, a more selective enzymatic esterification (Fig. 1.43) would have obvious benefits. Lipase-catalysed acylation is possible [126] but reaction rates are very low. This is mainly owing to the fact that the reaction, for thermodynamic reasons, cannot be performed in water. On the other hand, sucrose is sparingly soluble in most organic solvents, thus necessitating a slurry process. 

The esterase EPIO was highly selective for esterification of the L-isomer. Supercritical CO2 was the solvent for the reaction and for the postreaction separation of the acetate from the unreacted D-menthol. 

Selective reactions. Desilylation of triethylsilyl ethers in the presence of t-butyl-dimethylsilyl ethers is accomplished with a mesoporous silica in methanol at room temperature. Selective esterification of nonaromatic carboxylic acids using NaHS04-silica in methanol has also been described. ... 

When de-A-(f-butoxycarbonylation) is carried out in MeOH, esterification also occurs. Selective reaction of the primary amine in the presence of a secondary amine after trimethylsilylation of both has been demonstrated. The monosilylated primary amine is still derivatizable. 

The modification of the polymer backbone by selective reactions (halogena-tion, esterification, etherification, oxidation, reduction, Diels-AIder reactions, dehydrations, dehalogenations, cyclization, grafting [12], etc.) further extend the usefulness of a particular polymer. 

Catalytic processes are superior to processes that use stoichiometric reagents (Bechamp reduction cited earlier). There is a continuous improvement in catalysts. Many acid-catalyzed reactions (esterifications, hydrations, alkylations) have been replaced by benign ion exchange resins in the H form (Wasker and Pangarkar 1992, 1993). The newer catalysts are not only more selective but also more active in enhancing reaction rates. In some cases, for instance, replacement of mineral acids by ion exchangers allows the use of low-cost material of construction and facile separation/recycle of the catalyst while simultaneously eliminating ultimate neutralization of the product by a base. 

In the present study, selective substitution via chelates will be applied to etherification and esterification of sucrose. To be a homogenous substrate for a selective reaction, sucrose should give stoichiome-trically definable chelates that are sufficiently soluble in a dry aprotic solvent, such as N, N-dimethylfor-mcumide or dimethylsulphoxide. One might question whether the unchelated hydroxyl groups of sucrose also would be derivatized. 

A formal total synthesis of the proteasome inhibitor omuralide (71) has been reported by Kobayashi and co-workers involving a highly diastereoselective U-SCR." The condensation of y-ketoacid 64, p-methoxybenzylamine (65) and isonitrile 66 resulted in the y-lactam 67 as a single diastereomer. The source of the stereoselectivity in the reaction is rationalized by axial attack of the isonitrile with the intermediate iminium ion. In addition, the novel isonitrile 66 was developed and used in the reaction in order to avoid the difficulty associated with subsequent selective trans-esterification of the more hindered amide (C9 vs. Cl) in the Ugi product. Conversion of 68 to the 7V-acylindole 69 was accomplished under mildly acidic conditions. This intermediate was then treated with methanol and triethylamine to readily afford the neo-pentyl methyl ester 70 without observable methanolysis of the lactam functionality. 

The higher esterification rate of P- and y-carboxyl groups can be used for selective reactions. On the other hand the P- and y-carboxyl groups are more rapidly hydrolyzed in acid-catalyzed hydrolysis since protonation is facilitated by having the ammonium group further away from the carboxyl group. Alkali-catalyzed hydrolysis of methyl or ethyl esters of aspartic or glutamic acids bound to peptides can result in the formation of isopeptides. 

Acyl Formation Compared with hydrolysis reactions, esterification and transesterification reactions are much slower and require the use of activated esters to facilitate the reaction and to make it kinetically irreversible. These include trichloroethyl esters, trifluoroethyl esters, enol esters, thioesters and vinylcarbamates. Lipases isolated from Pseudomonas species are highly selective for the hydrolysis of esters of secondary alcohols, and therefore also for the corresponding reverse reactions. 

We previously mentioned the importance of determining the appropriate solvent for acyl transfer reactions (esterification and transesterification). Nevertheless, it is difficult to select a universal solvent for the esterification of (R,S) 2-arylpropionic acids. In fact, hydrophobic solvents such as cyclohexane [98,102], isooctane [97], or the mixtures isooctane/ChC or isooctane/toluene [100] are recommended for the highly hydrophobic substrates naproxen and ibuprofen (see Tables 6 and 7). On the contrary, moderately hydrophilic acids such as ketoprofen (Table 5 [92]) or flurbiprofen (Table 8 [111]) are better esterified in sUghtly hydrophilic solvents such as cffisopropyl ether, methylwobutyl ketone, or 1,4-dioxane. Iherefore, we can conclude that depending on the hydrophobicity of the substrate we must select the organic solvent in order to obtain the best catalytic performance. 

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