Carboxylic acid chlorides and anhydrides

The most common O- and N-acylation procedures use acylating agents that are more reactive than caiboxylic acids or their esters. Carboxylic acid chlorides and anhydrides react rapidly with most unhindered hydroxy and amino groups to give esters and amides, respectively ... 

The physical properties of a number of carboxylic acid chlorides and anhydrides are given in Tables 10.22, 10.23 and 10.24. 

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. 

Preparation of Carboxylic Acid Chlorides (and Anhydrides). Oxalyl chloride has found general application for the preparation of carboxylic acid chlorides since the reagent was introduced by Adams and Ulich. Acid chlorides produced by this means have subsequently featured in the synthesis of acyl azides, bromoalkenes, carboxamides, cinnolines, diazo ketones, (thio)esters, lactones, ketenes for cycloaddition reactions, intramolecular Friedel-Crafts acylation reactions, and the synthesis of pyridyl thioethers. ... 

Carboxylic acid fluorides from carboxylic acid chlorides and anhydrides... 

A large number of organic compounds, including aldehydes, ketones, lactones, carboxylic acids, chlorides and anhydrides, esters, amides, anilides and alcohols, ketals, epoxides, nitro compounds, glucose, ascorbic acid, and some ethers, have been analyzed by Dahn et al. (1959)... 

The chemistry of benzenecarboxyUc acids generally is the same as that of other carboxyUc acids, which can be converted into esters, salts, acid chlorides, and anhydrides. Each carboxyl group can react separately, so that compounds in which carboxyl groups are converted into different derivatives can be prepared. Because there are aromatic hydrogens available in most of these acids, they also undergo reactions characteristic of the benzene nucleus. Some of the anhydrides have characteristic reactions. 

At this stage, remember that carboxylic acids represent risks vis-a-vis esters, acid chlorides and anhydrides, amides or various sulphur-containing or phosphorated groups. 

Alternative reactions employ coupling reagents such as DCC (Steglich Esterification), preformed esters (transesterification), carboxylic acid chlorides or anhydrides. These reactions avoid the production of water. Another pathway for the production of esters is the formation of a carboxylate anion, which then reacts as a nucleophile with an electrophile (similar reactions can be found here). Esters may also be produced by oxidations, namely by the Baeyer-Villiger oxidation and oxidative esterifications. 

In the second step 20 is activated with oxalyl chloride to form a carboxylic acid chloride and treated in situ with a solution of (R)-4-benzyloxazolidine-2-thione 19 to produce 7 in 88 % yield. Alternatively the Crimmins group transformed 20 into a mixed pivalic anhydride 21 by means of pivaloyl chloride and triethylamine and converted it with the lithium salt of (7 )-4-benzyloxazolidin-2-one in 89 % yield to the corresponding oxazolidinone. In contrast to the sulfur analog, which is synthesized at temperatures between 0 °C and room temperature, the formation of an acyloxazolidinone had to take place at -78 °C. 

Acyl iodides.1 This reagent converts acyl chlorides into acyl iodides at 25°. In combination with iodine (1 1) it also converts carboxylic acids, esters, and anhydrides into acyl iodides in generally high yield. This reaction in combination with an alcohol is a useful method for transesterification of hindered alcohols. 

Sato et al. observed that the reaction of 2-phenyl-1-azirine with acid chlorides and anhydrides in the presence of triethylamine gives the oxazole directly.57 They have reported that azirines also react with carboxylic anhydrides to give oxazoles (136).57 Aziridine (135) is suggested as a likely intermediate in the reaction of acetic anhydride with azirine (42a), since carrying out the reaction at lower temperature and for a shorter reaction time gave a compound to which they assigned structure 135. 

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 the Friedel-Crafts acylation, carboxylic acid chlorides and carboxylic acid anhydrides are activated with stoichiometric amounts of A1C13 (Section 5.2.7). However, this activation is only possible in the presence of very weak nucleophiles such as aromatic compounds. Stronger nucleophiles would react with the A1C13 instead of the carboxylic acid derivative. If one wants to acylate such stronger nucleophiles—for example, alcohols or amines—with car-... 

The Figures 6.18 and 6.19 show SN reactions with H202 at the carboxyl carbon of carboxylic acid chlorides and one carboxylic acid anhydride. They are carried out in basic solution in order to utilize the higher reactivity of the HOO ion. All these reactions take place... 

Carboxylic and sulfonic acid chlorides and anhydrides give acylamino- and sulfonamidopyridines 748 and 749. Evidence exists that initial products of the reaction, the corresponding A -acyl-2-aminopyridinium salts, are unstable and rapidly rearrange to the thermodynamically more stable 2-acylaminoderivatives. 

The reaction mechanism for the hydrolysis of anhydrides is presumed to be similar to that described for acid chlorides (Scheme II). A notable difference between the reaction of acid chlorides and anhydrides, however, is the extent of reversibility in formation of 2. The reaction between 2 and chloride ion to give acid chloride (reversal of intermediate formation equation 2) is much less favored than the corresponding reaction between 2 and the carboxylate ion in both organic and aqueous phases. 

Thus, the carbonyl group of an acid chloride and anhydride, which are least stabilized by resonance, absorb at higher frequency than the carbonyl group of an amide, which is more stabilized by resonance. Table 22.4 lists specific values for the carbonyl absorptions of the carboxylic acid derivatives. 

Based on this order of reactivity, more reactive acyl compounds (acid chlorides and anhydrides) can be converted to less reactive ones (carboxylic adds, esters, and amides). The reverse is not usually true. 

Te-Esters of tellurocarboxylic acids were prepared from tellurolates and carboxylic acid chlorides or anhydrides, and from sodium telluride and aroyl chlorides". The following types of 7e-organo tellurocarboxylates have thus far been synthesized ... 

Benzimidoyl chlorides and )V, -dimethyl-)V -thiobenzoylfoimamidine react to afford thioimidic acid anhydrides (270 Scheme 40). Spirocyclic thioimino esters have been prepared from benzimidoyl chlorides and thiazolin-S-thiones.- Carboxylic acid imidothio acid anhydrides (271) can be synthesized from carboxylic acid chlorides and secondary thioamides. ... 

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