From Acid Chlorides and Anhydrides

Esters (and thioesters) have been prepared from 2-chlorocarbonylpyrazine and /3-dimethylaminoethanol in benzene (1278), lead methylmercaptide (and other mercaptans or mercaptides) (in ether at room temperature) (147, 1355) and thiophenol (in pyridine) (1356) from 2-chlorocarbonyl-3-methoxycarbonylpyrazine with methanol (1278) and from 2-dimethylaminoethanol (1278). 

Reduction of 2-chlorocarbonylpyrazine with lithium tri-t-butoxyaluminohydride in tetrahydrofuran gave 2-(pyrazin-2 -ylmethoxycarbonyl)pyrazine (1077). 

The preparation of some esters from the reactions of anhydrides has been described in Section 1C(4) and 2,3-dicarboxypyrazine anhydride with 2-dibutylamino-ethanol in refluxing benzene gave 2-carboxy-3-(2 -dibutylaminoethoxy)carbonyl-pyrazine (1278). 

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The formation of esters from acid chlorides and anhydrides according to the following equation has been discussed ... 

Amides are much more easily prepared from acid chlorides and anhydrides, as discussed in Sections 22.8 and 22.9. 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

AkoJwIs may be obtained from aldehydes, ketones, esters, acid chlorides, and anhydrides,... 

Preparation of acid anhydrides Acid anhydrides are prepared from carboxylic acids by the loss of water. For example, acetic anhydride is prepared industrially by heating acetic acid to 800 °C. Other anhydrides are difficult to prepare directly from the corresponding carboxylic acids. Usually they are prepared from acid chloride and sodium carboxylate salt (see below). 

Although acid chlorides and anhydrides can be easily hydrolysed to carboxylic acids, the reaction serves no synthetic purpose because acid chlorides and acid anhydrides are synthesised from carboxylic acids in the first place and they are also very reactive to be used as protecting groups. 

In Chapter 12 pyridine was often used as a catalyst in carbonyl substitution reactions. It can act in two ways. In making esters from acid chlorides or anhydrides pyridine can act as a nucleophile as well as a convenient solvent. It is a better nucleophile than the alcohol and this nucleophilic catalysis is discussed in Chapter 12 (p. 282). But nonnucleophilic bases also catalyse these reactions. For example, acetate ion catalyses ester formation from acetic anhydride and alcohols. 

Asymmetric Alkylation. 4-Pseudoephedrine ([IS, 2S]-(+)) is a commodity chemical employed in over-the-counter medications with annual worldwide production in excess of 300 metric tons. The enantiomer, /-pseudoephedrine, is also readily available in bulk and is inexpensive. Pseudoephedrine has been shown to be highly effective as a chiral auxiliary in asymmetric alkylation reactions. Treatment of either enantiomer of pseudoephedrine with carboxylic acid chlorides and anhydrides leads to efficient and selective iV-acylation to form the corresponding tertiary amide derivatives (Table 1). Typically, the only by-product in the acylation reactions is a small amount (<5%) of the A,0-diacylated product, which is easily removed by crystallization or flash column chromatography. Because intramolecular 0- -N acyl transfer within pseudoephedrine 3-amino esters occurs rapidly, and because the A-acyl form is strongly favored under neutral or basic conditions, products arising from (mono)acylation on oxygen rather than nitrogen are not observed. 

Acid anhydrides are synthesized from acid chlorides and carboxylic acid salts. 

Formation of acid anhydrides from acid chlorides and alkali salts of carboxylic acids is carried out by mixing the reactants and distilling off the anhydride formed. 

Zeolites have been used in the Friedel-Crafts acylation of (small) aromatics. While they perform well, pore-size constraints will limit their use - HBEA is generally the most active zeolite, but its largest channels are 7.6 Ax 6.4 A. With this material, acylations can be carried out with acid chlorides and anhydrides, with yields ranging from modest to veiy high. Substituting the Al centres for rare earths enhanced the activity of Y zeolites (Figure 4.3). ... 

DMSO/TBAF is highly efficient as a reaction medium for the homogeneous esterification of cellulose by transesterification and after the in situ activation (see below) of complex carboxylic acids. The acylation using acid chlorides and anhydrides is limited because the solution contains a certain amount of water caused by the use of the commercially available TBAF trihydrate and the residual moisture in the air-dried polysaccharides. Nevertheless, this system has shown a remarkable capacity for the esterification of lignocellulosic mataials, for example, sisal fibres, which contain about 14 per cent hemicellulose [28]. The DS values of cellulose acetate prepared from these fibres with acetic anhydride in mixtures of DMSO/TBAF were found to decrease with increasing TBAF concentration from 6 to 11 per cent (Table 16.4), due to the increased rate of hydrolysis both of the anhydride and the ester moieties. 

Anhydrides can also be prepared from acid chlorides and carboxylate salts in a reaction that occurs by a nucleophilic acyl substitution mechanism. This is a good method for preparing anhydrides derived from two different carboxylic acids, called mixed anhydrides. 

ALCOHOLS AND PHENOLS FROM CARBOXYLIC ACIDS, ACID CHLORIDES AND ANHYDRIDES... 

Because of a possible similarity between them and the group of reactions just dealt with, it is convenient to mention here some reactions which have been used to prepare carboxylic acid anhydrides. Minunni observed the formation of benzoic acid anhydride in high yield when benzoylpyridinium chloride was treated with water, and the reaction is generally useful . From the fatty acid series the reaction of heptoyl chloride with pyridine in benzene, followed by the addition of heptoic acid, provides an example of anhydride formation in high yield . More recently, anhydrides were prepared from acid chlorides and aqueous solutions of the corresponding sodium salts containing catalytic amounts of pyridine . It seems possible that... 

Diazomethane is a valuable and useful agent in organic synthesis that can be employed as a Ci building block in many single-step chemical reactions, for example, the methylation of alcohols or phenols, esteriflcations of carbonic adds, cyclopropanation reactions with alkenes, the synthesis of heterocycles, and the synthesis of a-diazoketones from acid chlorides or anhydrides. In general, the reactions proceed with release of nitrogen. Usually, diazomethane is freshly prepared from N-methyl-nitroso compounds and aqueous KOH solution and can be stored as a cooled solution for a couple of days. However, its low boiling point... 

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