Acid chlorides, esterification

The synthesis in (a) is achieved by a reductive amination reaction. Reactions in (b) include formation of an acid chloride, esterification, and reduction of the nitro group. 

Esterification of OH groups in methylol cellulose was studied. Ultimately, we wished to add long graft-like chains to the cellulose, so acid chlorides were the reactants of choice. Acetyl chloride was used as a model reactant. Here, DMSO cannot be used as a solvent because of its reactivity with acid chlorides. Esterifications were carried out by two methods, one involving direct reaction of acetyl chloride with methylol cellulose in DMF/LiCl using pyridine as acid acceptor. The pyridine was probably not necessary, though its equilibrium involvement with the acid chloride caused no apparent problem. 

Usually no difficulties are encountered in the esterification of thiazole acids. Direct esterification with alcohol and add in the presence of an acid catalyst (7, 61, 62), or prior conversion to the add chloride (6, 63, 64) followed by reaction with an alcohol in basic conditions give good yields. 

The most apparent chemical property of carboxylic acids their acidity has already been examined m earlier sections of this chapter Three reactions of carboxylic acids—con version to acyl chlorides reduction and esterification—have been encountered m pre vious chapters and are reviewed m Table 19 5 Acid catalyzed esterification of carboxylic acids IS one of the fundamental reactions of organic chemistry and this portion of the chapter begins with an examination of the mechanism by which it occurs Later m Sec tions 19 16 and 19 17 two new reactions of carboxylic acids that are of synthetic value will be described... 

Esterification of acid chlorides (Schotten-Baumann reaction) ... 

Rea.ctlons, As with other tertiary alcohols, esterification with carboxyUc acids is difficult and esters are prepared with anhydrides (181), acid chlorides (182), or ketene (183). Carbamic esters may be prepared by treatment with an isocyanate (184) or with phosgene followed by ammonia or an amine (185). 

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). 

Esterification. Alkylphenols react with acid chlorides and acids to produce commercially important esters. Three equivalents of -nonylphenol (10) react with phosphoms trichloride or tributyl phosphite to produce tris(4-nonylphenyl) phosphite (TNPP) (11). 

Esterification, Amidation, and Acid Chloride Formation. Amino acids undergo these common reactions of the carboxyl group with due regard for the need for A/-protection. 

The viscous fatty acid chloride is mixed with soHd sodium isothionate and is heated under vacuum and agitation without water or solvent HCl is evolved, leaving the product as a finely divided powder. The direct esterification of fatty acid and sodium isethionate has been patented (69). 

Reactions of the carboxyl group include salt and acid chloride formation, esterification, pyrolysis, reduction, and amide, nitrile, and amine formation. Salt formation occurs when the carboxyUc acid reacts with an alkaline substance (22)... 

Esters are most commonly prepared by the reaction of a carboxyHc acid and an alcohol with the elimination of water. Esters are also formed by a number of other reactions utilizing acid anhydrides, acid chlorides, amides, nitriles, unsaturated hydrocarbons, ethers, aldehydes, ketones, alcohols, and esters (via ester interchange). Detailed reviews of esterification are given in References 1—9. 

The acid chlorides are generally more reactive than the corresponding acid anhydrides. In fact, the alcoholysis of acid chlorides is probably the best laboratory method for preparing esters. Frequentiy, basic materials are added during the course of the reaction to neutralize by-product hydrochloric acid. When the basic material is aqueous caustic, the procedure is referred to as the Schotten-Baumann procedure (73). Esterification of tertiary alcohols by acid chlorides is described in Reference 74. Esters of tertiary alcohols can also be formed through an intermediate /-butyl thioate group (75) ... 

Orotic acid undergoes 5-nitration, 5-bromination in hydrobromic acid with peroxide, 5,5-dibromination following decarboxylation in bromine water, esterification, methylation (rather complicated), conversion into its acid chloride (containing some anhydride) by treatment with thionyl chloride, and conversion into 2,6-dichloropyrimidine-4-carboxylic acid by phosphoryl chloride (62HC(16)422). 

The chemical inertness of the three-membered ring permitted many conversions of functional groups in diazirines. Esterifications, cleavage of esters and acetals, synthesis of acid chlorides, oxidation of hydroxy groups to carboxyl groups as well as Hofmann alkenation all left the three-membered ring intact (79AHC(24)63). 

Pyrimidinecarboxylic acid chlorides formation, 3, 80 Pyrimidinecarboxylic acids acidic pK , 3, 60 decarboxylation, 3, 80 esterification, 3, 80 esters... 

The choice of which reactions to include is not an easy one. First there are the well known "Name Reactions", that have appeared in various monographs or in the old Merck index. Some of these are so obvious mechanistically to the modern organic chemistry practitioner that we have in fact omitted them for instance esterification of alcohols with acid chlorides - the Schotten-Baumann procedure. Others are so important and so well entrenched by name, like the Baeyer-Villiger ketone oxidation, that it is impossible to ignore them. In general we have kept older name reactions that are not obvious at first glance. 

This method with some slight modihcations is applied in the synthesis of to-bromo esters from Cs to Cn. Methyl 5-bromovalerate has been prepared by treating the silver salt of methyl hydrogen adipate with bromine. The ethyl ester has been prepared from the acid by esterification or through the acid chloride. ... 

Normal Fischer esterification of tertiary alcohols is unsatisfactory because the acid catalyst required causes dehydration or rearrangement of the tertiary substrate. Moreover, reactions with acid chlorides or anhydrides are also of limited value for similar reasons. However, treatment of acetic anhydride with calcium carbide (or calcium hydride) followed by addition of the dry tertiary alcohol gives the desired acetate in good yield. 

Problem 21.10 Which method would you choose if you wanted to prepare cyclohexyl benzoate— Fischer esterification or reaction of an acid chloride with an alcohol Explain. 

Esters are usually prepared from carboxylic acids by the methods already discussed. Thus, carboxylic acids are converted directly into esters by SK2 reaction of a carboxyfate ion with a primary alkyl halide or by Fischer esterification of a carboxylic acid with an alcohol in the presence of a mineral acid catalyst. In addition, acid chlorides are converted into esters by treatment with an alcohol in the presence of base (Section 21.4). 

Esterification is normally carried out by treating the carbohydrate with an acid chloride or acid anhydride in the presence of a base (Sections 21.4 and 21.5). All the —OH groups react, including the anomeric one. For example, /3-o-glucopyranose is converted into its pentaacetate by treatment with acetic anhydride in pyridine solution. 

As sulfonic acid cannot be vaporized, its determination by the direct gas chromatography (GC) method is not possible. To enable determination by GC, the reactivity of the S03H group is used the esterification of the S03H group with diazomethane via acid chloride is one way to transfer the sulfonic acid to volatile compounds. By conversion of the sulfonic acid with phosphoric acid at 200-210°C, the S03H group is cleaved and the hydrocarbons are obtained [184-186]. 

Dzulkefly, K Koon, S. Y. Kassim, A. Sharif, A. and Abdullah, A. H. (2007). Chemical modification of SAGO starch by solventless esterification with fatty acid chlorides. The Malaysian. Analy. Set, 11,395-399. 

Alternatively, esterification of carboxylic acid can be carried out in aqueous media by reacting carboxylic acid salts with alkyl halides through nucleophilic substitutions (Eq. 9.10).20 The reaction rate of alkyl halides with alkali metal salts of carboxylic acids to give esters increases with the increasing concentration of catalyst, halide, and solvent polarity and is reduced by water. Various thymyl ethers and esters can be synthesized by the reactions of thymol with alkyl halides and acid chlorides, respectively, in aqueous medium under microwave irradiation (Eq. 9.11).21 Such an esterification reaction of poly(methacrylic acid) can be performed readily with alkyl halides using DBU in aqueous solutions, although the rate of the reaction decreases with increasing water content.22... 

A further example is given in reference [88] Selective esterification of retronecine, the dialcoholic component of a pyrolizidine alkaloid, by the imidazolide method was found to be superior to the acid chloride/pyridine method. Acylation of the 9-position of retronecine with tiglic acid, pivalic acid, isobutyric acid, and propionic acid was investigated concerning the steric requirement of the carboxylic acid. 

One of the mainstays in the treatment of tuberculosis is paraaminosalicylic acid (PAS). It is not, however, a pleasant drug to take. Phenyl aminosalicylate (20) was synthesized from 4-nitrosalicylic acid (18) by esterification of its acid chloride with phenol to give 19, which is converted to the desired... 

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