1,1-Dicarboxylic esters, acylation

The solvent present in biphasic reactions can still have an effect on the enzyme even though the enzyme functions primarily in an aqueous microenvironment. A particularly dramatic example is the lipase AH (lipase from Burkholderia cepac/fl)-catalysed desym-metrization of prochiral 1,4-dihydropyridine dicarboxylic esters, where either enantiomer can be accessed in high enantioselectivity by using either water-saturated cyclohexane or diisopropyl ether (DIPE) respectively (Scheme 1.60). The acyl group used in acylation and deacylation can also have a dramatic effect on enantioselectivity. " ... 

Acid esters are useful synthetic intermediates. For example, their use in the synthesis of long-chain dicarboxylic esters by electrolytic (anodic) synthesis has already been noted (Expt 5.131). Furthermore the reaction of the acid ester with thionyl chloride in the usual way will convert the carboxylic acid grouping to an acyl chloride group thus yielding the synthetically useful ester-acyl chloride the products are usually purified by distillation under reduced pressure. 

Hydrogen atoms on the central carbon atom of 1,3-diimine or iminato macrocycles (36) (38) (and of their 1,3-diketone or 1,3-dicarboxyl ester precursors) undergo facile substitution, leading to 6- or 6,13-substituted cyclams (or oxo-cyclams), and their homologues. The acyl substituent groups of Jaeger tetraazamacrocycles (35) are readily substituted. 

A one-pot synthesis of furan 2-substituted-3-carboxylic and 2-substituted-3,4-dicarboxylic esters was reported. Thus, reaction of an acyl isocyanate with trimethylsilyldiazomethane, a safe replacement for hazardous diazomethane, gave 2-substituted oxazoles, which were treated with dimethyl acetylenedicarboxylate or ethyl propiolate to afford the corresponding di- and trisubstituted furans in good yields <04S1359>. 

A variety of external plasticizers have also been suggested for cyanoacrylates. Among these are alkyl esters of aliphatic monocarboxylic acids such as cyanoacetates aliphatic dicarboxylic esters, such as malonates, adipates, and sebacates triaromatic phosphates such as tricresyl phosphate acyl triesters of glycerine dialkyl alkylphosphonates and alkyl phthalates. Joyner and Coover state that limiting the plasticizer concentration to less than 5% will not retard the cure speed, from 5 to 20% will retard the cure rate, and over 20% plasticizer concentration seriously slows the cure rate of the adhesive. 

Pyrazolo[l,5-a]pyridine-2,3-dicarboxylic acid dimethyl ester synthesis, 5, 153 Pyrazolopyridines acylation, 5, 311 6-fused... 

Claisen ester condensation, 6, 279 Thiazolecarboxylic acid chlorides reactions, 6, 279-280 Thiazolecarboxylic acid hydrazides synthesis, 6, 280 Thiazolecarboxylic acids acidity, 6, 279 decarboxylation, 6, 279 reactions, S, 92 6, 274 Thiazole-2-carboxylic acids decarboxylation, S, 92 Thiazole-4-carboxylic acids stability, S, 92 Thiazole-5-carboxylic acids decarboxylation, S, 92 Thiazole-4,5-dicarboxylic acid, 2-amino-diethyl ester reduction, 6, 279 Thiazole-4,5-dicarboxylic acids diethyl ester saponification, 6, 279 Thiazolediones diazo coupling, 5, 59 Thiazoles, 6, 235-331 ab initio calculations, 6, 236 acidity, S, 49 acylation, 6, 256 alkylation, S, 58, 73 6, 253, 256 analytical uses, 6, 328 antifogging agents... 

Dicarboxylic acids have been prepared by the stepwise acylation and Wolff-Kishner reduction of thiophene or di-2-thienylmethane with ester chlorides of dicarboxylic acids. Another method consists of the AICI3 catalyzed acylation of w-phenylalkylthiophenes which occurs both in the free thiophenic position and in the para position of the ring (226). Hypochlorite oxidation and desulfurization then give diacides such as (227)... 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Liquid crystal polyesters are made by a different route. Because they are phenolic esters, they cannot be made by direct ester exchange between a diphenol and a lower dialkyl ester due to unfavorable reactivities. The usual method is the so-called reverse ester exchange or acidolysis reaction (96) where the phenolic hydroxyl groups are acylated with a lower aliphatic acid anhydride, eg, acetic or propionic anhydride, and the acetate or propionate ester is heated with an aromatic dicarboxylic acid, sometimes in the presence of a catalyst. The phenolic polyester forms readily as the volatile lower acid distills from the reaction mixture. Many liquid crystal polymers are derived formally from hydroxyacids (97,98) and their acetates readily undeigo self-condensation in the melt, stoichiometric balance being automatically obtained. 

Monocationic acyl ions are readily prepared as persistent species in solutions of low nucleophile strength.68 These acyl ions have been thoroughly characterized by IR and NMR spectroscopy, and several acyl ion salts have been characterized by X-ray crystallography. The monocationic acyl ions are often prepared in situ from carboxylic acids, esters, or anhydrides, by the action of a strong Brpnsted acid, or the ions can be prepared from ionization of an appropriate acid halide with a strong Lewis acid. Both methods have been used to prepare acyl-centered dications, some of which can be considered distonic superelectrophiles. As described previously, dicarboxylic acids cleave to the bis-acyl ions in superacid (FSChH-SbFs) provided that the acyl cations are separated by at least three methylene units (eq 54).55 The first bis-acyl dications were reported by Olah and Comisarow, being prepared by the reactions of dicarboxylic acid fluorides with superacidic SbFs (eq 72).69... 

This reaction provides a useful way of introducing a double bond next to a carbonyl group. Here it is in a synthesis by Barry Trost of the Queen Bee Substance (the compound fed by the workers to those bee larvae destined to become queens). The compound is also a pheromone of the termite and is used to trap these destructive pests. Trost started with the monoester of a dicarboxylic acid, which he converted to a methyl ketone by reacting the acyl chloride with a cuprate. The ketone was then protected as a dioxolane derivative to prevent it enolizing, and the sulfur was introduced by reacting the enolate of the ester with the sulfur electrophile MeSSMe. 

The oxidation of 1,4-dicarboxylic acids with LTA in benzene results in double decarboxylation with the formation of a double bond (equation 16). Similarly, the pyrolysis of the di-r-butyl peroxy esters of 1,4-dicarboxylic acids in high boiling solvents leads to the formation of double bonds (equation 17). The method is especially useful in so far as 1,4-diacids are readily available from Diels-Alder reactions using derivatives of mtdeic and fumaric acid as the dienophile. Apparently, application of the 0-acyl thiohydroxamate method to 1,4-diacids does not result in the formation of double bonds but rather in the product of double decarboxylative rearrangement (Section S.4.6.1). ... 

When the spiro-activated cyclopropane (479) is heated with aqueous acetone a 9 1 mixture of the lactone (482) and the dicarboxylic acid (480) is obtained. Thus, with water as a nucleophile, ring cleavage is faster than acylal cleavage. Presumably, the spiroacylal functions as an active ester in the cyclization of the initially formed 1,5-adduct (481) (equation 164) °. ... 

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