Active esterification

The placement of a nitrogen atom directly on the benzilic carbon atom is apparently consistent with antispasmodic activity. Esterification of 2 (iV-piperidyl)ethanol by means of chloroacyl chloride (68) gives the basic ester (69). Displacement of the remaining halogen by piperidine gives dipiproverin (70). ... 

Derivatives. A considerable number of compounds that contain the benzenehexol structure possess therapeutic activity. Esterification of benzenehexol with a pyridinecarbonyl chloride gives the corresponding hexaesters, which are antiatherogenics (267). Tetroquinone [319-89-1] (tetxahydroxy-/>-benzoquinone) is administered orally for the treatment of keloids. The dipotassium salt of rhodizonic acid (80) is useful as a remedy for diabetes mellitus (262). Compounds, eg (81) and (82), which are derived from rhodizonic acid, are useful as antiinflammatory agents and diuretics (qv) (268). 

The most relevant methodologies of reaction for the formation of esters, which are also used in the context of PVMRs for esterification, are hereafter proposed. For the purpose of this work, information about Lewis acid-activators, esterification base-activators, carbodiimide activators, the Mitsunobu reaction, induced activation of the condensation reaction using template compounds, and other reaction methodologies between carboxylic acids and alcohols used in ester synthesis will not be proposed. For this information, the reader is referred to the literature (Otera, 2003). 

Another series of antiinflammatory carboxyhc acids that ate derived from cortienic acid (107), a minor adrenal metabohte, has been described (104,105). Esterification of both the 17a-hydroxyl group and the carboxyhc acid of (107) were requited to develop a compound of high topical potency with low systemic activity. Peak activity was generally associated with a 17a-propionoxy group and a 17P- uoromethoxy carbonyl (eg, (108)), or 17P-methoxycarbonyl residue. 

Acidic Cation-Exchange Resins. Brmnsted acid catalytic activity is responsible for the successful use of acidic cation-exchange resins, which are also soHd acids. Cation-exchange catalysts are used in esterification, acetal synthesis, ester alcoholysis, acetal alcoholysis, alcohol dehydration, ester hydrolysis, and sucrose inversion. The soHd acid type permits simplified procedures when high boiling and viscous compounds are involved because the catalyst can be separated from the products by simple filtration. Unsaturated acids and alcohols that can polymerise in the presence of proton acids can thus be esterified directiy and without polymerisation. 

Many of the physical properties are not affected by the optical composition, with the important exception of the melting poiat of the crystalline acid, which is estimated to be 52.7—52.8°C for either optically pure isomer, whereas the reported melting poiat of the racemic mixture ranges from 17 to 33°C (6). The boiling poiat of anhydrous lactic acid has been reported by several authors it was primarily obtained duriag fractionation of lactic acid from its self-esterification product, the dimer lactoyUactic acid [26811-96-1]. The difference between the boiling poiats of racemic and optically active isomers of lactic acid is probably very small (6). The uv spectra of lactic acid and dilactide [95-96-5] which is the cycHc anhydride from two lactic acid molecules, as expected show no chromophores at wavelengths above 250 nm, and lactic acid and dilactide have extinction coefficients of 28 and 111 at 215 nm and 225 nm, respectively (9,10). The iafrared spectra of lactic acid and its derivatives have been extensively studied and a summary is available (6). 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Dimethylaminopyridine [1122-58-3] (DMAP) (24) has emerged as the preferred catalyst for a variety of synthetic transformations under mild conditions, particularly acylations, alkylations, silylations, esterifications, polymeri2ations, and rearrangements (100). POLYDMAP resin [1122-58-3], a polymeric version of DMAP, is available, and is as effective as DMAP as a catalyst for acylation reactions. Furthermore, it can be recycled without regeneration more than 20 times with very Htde loss in activity. POLYDMAP is a trademark of Reilly Industries, Inc. 

Highly cross-linked polyol polytitanates can be prepared by reaction of a tetraaLkyl titanate with a polyol, such as pentaerythritol, followed by removal of the by-product alcohol (77). The isolated soHds are high activity catalysts suitable for use in the preparation of plasticizers by esterification and/or transesterification reactions. The insoluble nature of these complexes faciUtates their... 

The alkoxy titanate compounds formed by reaction of one mole of tetraalkyl titanate with one mole of a dialkanolamine are excellent esterification catalysts for the manufacture of phthalate-based plasticizers (112). If a 1 1 molar mixture of alkanolamine and water is used ia place of the alkanolamine, oligomeric titanate complexes are formed, which have high catalyst activity and can be used as thixotropic additives to paints and other aqueous coating formulations (113). 

Sorbitol is the most important higher polyol used in direct esterification of fatty acids. Esters of sorbitans and sorbitans modified with ethylene oxide are extensively used as surface-active agents. Interesteritication of fatty acid methyl esters with sucrose yields biodegradable detergents, and with starch yields thermoplastic polymers (36). 

Cellulose activated with ethylenediarnine [107-15-3] is used to prepare high molecular-weight cellulose butyrate (23). Cellulose so activated has a larger measured surface area (120 m /g) than cellulose activated with acetic acid (4.8 m /g). The diamine is removed with water, followed by solvent exchange with acetic acid and butyric acid before esterification. 

Ethylenediamine (70,71), benzyl alcohol and acetone (72), ethylene glycol (73) and C2—C g carboxyUc acids (74) are claimed to increase the reactivity of cellulose toward acetylation. Sodium hydroxide and Hquid ammonia (71) are excellent swelling agents and have been used to activate cellulose before esterification. Ultrasonic treatment of cellulose slurries (75) reportedly swells the fibers and improves reactivity. 

Use of Desiccants and Chemical Means to Remove Water. Another means to remove the water of esterification is calcium carbide supported in a thimble of a continuous extractor through which the condensed vapor from the esterification mixture is percolated (41) (see Carbides). A column of activated bauxite (Elorite) mounted over the reaction vessel has been used to remove the water of reaction from the vapor by adsorption (42). 

In the case of ethylene, it is necessary to use high temperatures and pressures as well as active catalyst to effect esterification (82). Yields of 40—50% based on ethylene were obtained with boron trifluoride—hydrogen fluoride mixtures as catalysts at 150°C. 2-Butene under pressure at 115—120°C with an excess of glacial acetic acid containing 10% H2SO4 gave as much as a 60% yield of I -butyl acetate (83). 

The chemistry of ethyl alcohol is largely that of the hydroxyl group, namely, reactions of dehydration, dehydrogenation, oxidation, and esterification. The hydrogen atom of the hydroxyl group can be replaced by an active metal, such as sodium, potassium, and calcium, to form a metal ethoxide (ethylate) with the evolution of hydrogen gas (see Alkoxides, metal). 

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