Esters preparation from alcohols with acyl chlorides

Section 20 7 Esters occur naturally or are prepared from alcohols by Fischer estenfi cation or by acylation with acyl chlorides or acid anhydrides (see Table 20 3)... 

Section 19.6 Esters occur naturally or are prepared from alcohols by Eischer esterification or by acylation with acyl chlorides or acid anhydrides (see Table 19.3). Esters are polar and have higher boiling points than alkanes of comparable size and shape. Esters don t form hydrogen bonds to other ester molecules so have lower boiling points than analogous alcohols. They can form hydrogen bonds to water and so are comparable to alcohols in their solubility in water. 

As a dibasic acid, malic acid forms the usual salts, esters, amides, and acyl chlorides. Monoesters can be prepared easily by refluxing malic acid, an alcohol, and boron trifluoride as a catalyst (9). With polyhydric alcohols and polycarboxyUc aromatic acids, malic acid yields alkyd polyester resins (10) (see Alcohols, polyhydric Alkyd resins). Complete esterification results from the reaction of the diester of maUc acid with an acid chloride, eg, acetyl or stearoyl chloride (11). 

Tertiary alkyl azides can be prepared by stirring tertiary alkyl chlorides with NaN3 and ZnCl2 in 82 ° or by treating tertiary alcohols with NaN3 and CF3-COOH or with HN3 andTiCl4 or BF3. Acyl azides, which can be used in the Curtius reaction (18-14), can be similarly prepared from acyl halides, anhydrides, " esters, or other acyl derivatives. ° Acyl azides can also be prepared... 

Acyl chlorides are prepared from acids and either SOCI2 or PCI5. They react rapidly with water to give acids, with alcohols to give esters, and with ammonia to give amides. 

Esters are readily prepared by reaction of an alcohol with either an acyl chloride or an anhydride. Because it is more easily prepared from the acid, the acyl chloride is commonly employed. Again, a base, such as pyridine, is often added to react with the HC1 that is produced. Acetic anhydride, which is commercially available, is often used for the preparation of acetate esters. Following are several examples. 

Cyanuric chloride has been used for the preparation of acyl chlorides, amides, and peptides. Conversion of cyanuric chloride into 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT, 6) leads to a reagent that upon reaction with carboxylic acids produces the highly reactive 2-acyloxy-4,6-dimethoxy-l,3,5-triazines.P l The resulting active ester is a powerful acylating agent for alcohols and amines. The activation is performed in presence of a base, preferentially NMM, which leads to intermediate formation of 4-(4,6-dimethoxy-l,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM, 7)P l (Scheme 5). This addition product is readily prepared from the commercially available CDMT (6) and NMM in THF and can be stored as solid compound in the cold.P P l It offers the advantage that it can be used in a one-... 

From a historical perspective, the a-(dialkylamino)nitrile anions were the first acyl anion equivalents to undergo systematic investigation. More recent studies indicate that anions of a-(dialkylamino)nitriles derived from aliphatic, aromatic or heteroaromatic aldehydes intercept an array of electrophiles including alkyl halides, alkyl sulfonates, epoxides, aldehydes, ketones, acyl chlorides, chloroformates, unsaturated ketones, unsaturated esters and unsaturated nitriles. Aminonitriles are readily prepared and their anions are formed with a variety of bases such as sodium methoxide, KOH in alcohol, NaH, LDA, PhLi, sodium amide, 70% NaOH and potassium amide. Regeneration of the carbonyl group can be achieved... 

Identification of Acyl Chlorides.—The reactions of acyl chlorides which are most helpful in their identification, are those which take place when they are treated with water, with alcohol, and with ammonia. Reaction takes place readily with these substances. When an acyl chloride is mixed with a small quantity of water or alcohol, hydrogen chloride is evolved. In the case of certain chlorides gentle heat is necessary to bring about reaction. The physical properties of the chloride together with those of the acid, ester, or amide prepared from it serve to complete its identification. 

It has been stressed that the presence in a benzene derivative of two bulky substituents, such as chlorines ortho with respect to the reaction site may cause severe steric hindrance. As expected, the perchloroaryl carboxylic acids are not esterified by Meyer s acid-catalysed procedure either, although their methyl esters are readily prepared with diazomethane (Riera, 1961). In general, the synthesis of alkyl esters is successfully performed by acylation of alcohols with the overcrowded acid chlorides, the latter being obtained smoothly from the corresponding acids with thionyl chloride. 

Chattopadhyay and Pattenden first demonstrated the viability of such a synthetic strategy in a model system designed to construct the basic tris-oxazole core. The oxazole amino alcohol 1573 was prepared from Gamer s acid " 1572 in four steps (Scheme 1.401). Serine benzyl ester was the starting material for 2-(acetoxymethyl)-4-oxazolecarbonyl chloride 1574. Acylation of 1573 with 1574 produced the bis-oxazole amide 1575. The differentially functionalized model tris-oxazole 1576 was then prepared from 1575 in two straightforward steps. 

Esterification.—iVAWW -Tetramethylchloroformamidinium chloride, which is readily prepared from iVAWW -tetramethylurea and oxalyl chloride, is an efficient reagent for the esterification of carboxylic acids with alcohols yields of between 66 and 97% are obtained, and the method has also been applied to macrolide synthesis. A modified one-pot procedure for the esterification of carboxylic acids, using phenyl dichlorophosphate-dimethylformamide complex, has appeared. A simple method of activation of carboxylic acids, using methanesulphonyl chloride and triethylamine followed by addition of the alcohol and 4-dimethylaminopyridine, leads to esters in 57— 96% yield for thirteen examples. 0-Methylcaprolactim reacts with carboxylic acids to give methyl esters in 73—91 % yield for seven examples and 2-iodoethyl esters are prepared from acyl chlorides, ethylene oxide, and sodium iodide. Transesterification, catalysed by titanium(iv) alkoxides, provides an effective method for synthesis of esters. Diethyl trichloromethylphosphonate reacts with carboxylic acids to give ethyl esters via transesterification, in 52 to 98 % yield. ... 

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