Esterification of Alcohol

To an organic chemist, the term ester normally means an ester of a carboxylic acid, unless some other kind of ester is specified. Replacing the —OH group of a carboxylic acid with the —OR group of an alcohol gives a carboxylic ester. The following reaction, called the Fischer esterification, shows the relationship between the alcohol and the acid on the left and the ester and water on the right. 

For example, if we mix isopropyl alcohol with acetic acid and add a drop of sulfuric acid as a catalyst, the following equilibrium results. 

---

Catalytic esterification of alcohols and acids in the vapor phase has received attention because the conversions obtained are generally higher than in the corresponding liquid-phase reactions (7). 

Inter and Intramolecular nucleophiKc displacement o< alcohols wHh inversion by means of cHethyi azo cartMxylate (DEAD)-triphenylphosphine and a nucleophile. Also dehydration, esterification of alcohols or alkylallon of phenols,... 

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. 

Phase-transfer catalysed esterification of alcohols and phenols with acid chlorides... 

Less reactive than acyl halides, but still suitable for difficult couplings, are symmetric or mixed anhydrides (e.g. with pivalic or 2,6-dichlorobenzoic acid) and HOAt-derived active esters. HOBt esters smoothly acylate primary or secondary aliphatic amines, including amino acid esters or amides, without concomitant esterification of alcohols or phenols [34], HOBt esters are the most commonly used type of activated esters in automated solid-phase peptide synthesis. For reasons not yet fully understood, acylations with HOBt esters or halophenyl esters can be effectively catalyzed by HOBt and HOAt [3], and mixtures of BOP (in situ formation of HOBt esters) and HOBt are among the most efficient coupling agents for solid-phase peptide synthesis [2]. In acylations with activated amino acid derivatives, the addition of HOBt or HOAt also retards racemization [4,12,35]. 

Esterification of alcohols using heterogeneous acid catalyst... 

Carvoli G, Gelosa D, Morbidelli M, Ranghino G, Ruggieri R, Tricella A. Process for the esterification of alcohols in a chromatographic reactor. EP 1213278, La Chemial Spa, 2002. 

Various lipases and esterases have been used for the enantioselective esterification of alcohols and hydrolysis of esters. For example, Burkholderia cepacia lipases (PS, Amano Enzyme Inc.) and Candida antarctica lipase (CAL, Novozymes) have been widely used for its wide substrate specificities, high activities and chemo, regio and enantioselectivities. Fundamentals and some selected applications are shown in this section. The origins and abbreviations of lipases introduced here are as follows. 

Hydrolytic enzymes can also catalyzed the esterification of alcohols or acids with hetero atoms.1617 Some examples for the reactions of phosphorous and sulfur compounds by lipases are shown in Figure 16. By the repeated enantioselective acylation and hydrolysis of a hydroxyl phosphonate and its acetate with lipase AH, phosphonic acid analogue of carnitine (essential cofactor of fatty acid metabolism), (A)-phosphocarniiine, and its enantiomer were synthesized as shown in Figure 16 (b). 

It has also been found that for my nitric acid concentration, the nitration rate is nearly proportional to the molar excess of sulphuric acid as related to the water content of the nitrating mixture. The nitrating acid excess is a factor of special importance in esterification of alcohols ( O-nitration ),... 

Scandium triflate (Sc(OTf)3), which is commercially available, is a practical and useful Lewis acid catalyst for acylation of alcohols with acid anhydrides or the esterification of alcohols by carboxylic acids in the presence of... 

A key example of the usefulness of charged tags in probing reaction mechanisms is found in our study of the esterification of alcohols and carboxylic acids [90] reportedly catalyzed by dis-tannoxanes [91]. A permanently-charged pyridinium group was... 

The continued use of pyridine as the usual solvent for sulfonyla-tions is justified by the well known catalytic effect of pyridine on esterification of alcohols. A discussion of such reactions has been presented by Foster and coworkers in which the possibility is considered that complexes of pyridine with sulfonyl chlorides are responsible for the catalytic effect of pyridine. In a study of the reaction of l,2 5,6-di-0-isopropylidene-a-D-glucofuranose with methanesulfonyl chloride, the corresponding 3-methanesulfonate was formed in 88% yield widi pyridine as solvent, but in only 45% yield with triethylamine or tributylamine. In some methanesulfonylations of methyl glycopyranosides, mixtvures of pyridine and triethylamine, and of pyridine and N,2V-dimethylformamide, have been used " to... 

The carbonates, sulphates, and borates are decomposed. The sulphides of the alkalies and alkaline earths are decomposed while the sulphides of arsenic, antimony, molybdenum, zinc, cadmium, tin, iron, lead, copper, mercury, and palladium are not attacked. Cobalt sulphate is not attacked, while the sulphates of the alkalies and alkaline earths are attacked and dissolved. Alkali tungstates, ammonium arsenite and arsenate, copper arsenite, ammonium magnesium arsenate, ammonium molybdate and vanadate, potassium cyanide and ferrocyanide are decomposed. Paraffin is not attacked shellac, gum arabic, gum tragacanth, copal, etc., are decomposed. Celluloid is slowly attacked. Silk paper, gun cotton, gelatin, parchment are dissolved. M. Meslans 22 has studied the esterification of alcohol by hydrofluoric acid. 

The major subgroups of anionic surfactants include the alkali carboxylates (soaps), sulfates, sulfonates, and to a smaller degree, phosphates. The esterification of alcohol with sulfuric acid yields probably the best-studied surfactant, sodium dodecylsulfate or SDS. SDS, a sulfate ester, is an extremely effective emulsifier because of its high-electrostatic repulsion. Other sulfates are, for example, sulfated esters from fatty acids, sulfated ethers, and sulfated fats and oils. Sulfonates stem from the reaction of sulfonic acid with suitable substrates. Members of the class of sulfonates are, for example, sulfonic acid salts or aliphatic sulfonates. Other anionic surfactants include substances such as carboxylated soaps and esters of phosphoric acid. 

Use Preparation of substituted amines and amides, acid anhydrides, esterification of alcohols, synthesis of other organic compounds. 

In contrast to the oxidative deavage of the C10-C11-moiety, hydroboration followed by oxidation furnishes Cll-functionalized quinine and quinidine derivatives. As an illustration, only transformations in the quinidine series are shown (cf. Scheme 12.14). Cll-aldehyde 58 was obtained either upon direct oxidation of the borane species with PCC/Si02 or via an improved stepwise procedure including (i) oxidation with Me3NO-2 H20 to yield the terminal alcohol 57 and (ii) subsequent Dess-Martin oxidation [35], Oxidation and esterification of alcohol 57 using Jones reagent and MeOH/HCl gave the Cl 1-ester 59, which is a suitable precursor for the synthesis of cinchona alkaloid macrocycles (Scheme 12.15) [38],... 

Sulfate can be converted to the sulfate donor compound 3 -phosphoadenosine-5 -phosphosulfate (PAPS) in a two-step reaction (Figure 17-17). PAPS participates in the sulfate esterification of alcoholic and phenolic functional groups (e.g., in synthesis of sulfolipids and glycosamino-glycans). 

Esterification of alcohols is also effected in good yields by using the mixed anhydride prepared from trifluoroacetic anhydride and dialkyl l-(hydroxycarbonyl)methylphosphonate (CH2CI2,... 

Organotin alkoxides are employed for the etherification and esterification of alcohols, the latter of which is also applied to the macrolide synthesis (eq (117)) [112]. 

The main use of methyl chlorides is for the production of higher chlorinated methanes. It also is used as a solvent and for many chemical reactions. It is used in the methylation or esterification of cellulose, which is used as industrial gum. Chloroform also is used in the esterification of alcohols. The scheme is as follows ... 

---