Carboxylic acid from acyl chlorides

The mechanism is similar to that for the formation of chlorides from alcohols and thionyl chloride. The hydroxyl group is converted to a good leaving group by thionyl chloride, followed by a nucleophilic acyl substitution in which chloride is the nucleophile (compare with Sec. 7.10). Phosphorus pentachloride and other reagents can also be used to prepare acyl chlorides from carboxylic acids. 

The main applications of oxalyl chloride, as described in Chapter 4, are the formation of aryl isocyanates and chloroformates (by reactions with amines and hydroxylic substrates, respectively), and the formation of acyl chlorides from carboxylic acids under very mild conditions. Oxalyl chloride reacts with amides to give acyl isocyanates, and it is used with dimethyl sulfoxide as a mild reagent for the oxidation of alcohols (Swern-type oxidation). It is also used with N,N-dimethylformamide as a mild reagent for chlorination and formylation. Oxalyl chloride is widely used in commercial formulations of speciality polymers, antioxidants, photographic chemicals, X-ray contrasting agents, and chemiluminescent materials. Other physical properties are presented in Chapter 3. 

It should be mentioned at this stage that instead of acyl chlorides, mixed anhydrides may also be used for the synthesis of acyl azides. From carboxylic acids and chloroformates/triethylamine, mixed anhydrides are formed, which can directly react with azide ions. Sterically hindered acids fail in this procedure (equation 31)." " The similar synthesis of /-butyl azidoformate by reaction of /-butylcarbonic diethylphosphoric anhydride with KN3 is described in Organic Syntheses. ... 

V-Dimethylchlorosulfitomethaniminium chloride (54), prepared from thionyl chloride and dimethyl-formamide, together with sodium azide is useful for the direct preparation of acyl azides from carboxylic acids (equation 35). ... 

Acyl peroxides from carboxylic acids via carboxylic acid chlorides... 

Acyl cyanides from carboxylic acid chlorides s. 3, 689 5, 566 COC1 COCN... 

Acyl peroxides from carboxylic acid chlorides 2 COC1 —V CO-Og-OC s. 5,95... 

Reactions of carboxylic acid chloride-pyridine addition compounds Carboxylic acid anhydrides and acyl sulfides from carboxylic acid chlorides... 

Because acylation of amines with acyl chlorides and anhydrides yields an acid as one of the products (HCl from acyl chlorides, a carboxylic acid from an anhydride), the efficient synthesis of amides requires some attention to stoichiometry. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

Acyl chlorides are readily available They are prepared from carboxylic acids by reaction with thionyl chloride... 

The chemistry of the carbonyl group is probably the single most important aspect of organic chemical reactivity Classes of compounds that contain the carbonyl group include many derived from carboxylic acids (acyl chlorides acid anhydrides esters and amides) as well as the two related classes discussed m this chapter aldehydes and ketones... 

In addition to acyl chlorides and acyl bromides, there are a number of milder and more selective acylating agents which can readily prepared from carboxylic acids, hnidazolides, the /V-acyl derivatives of imidazole, are examples.108 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with... 

Acyl Meldrum s acids (83TH1 87TH1), easily accessible from carboxylic acid chlorides and Meldrum s acid, may be viewed as protected 3-oxo-carboxylic acid esters (78JOC2087). The latter offer the advantage... 

The most important reactions of carboxylic acids are the conversions to various carboxylic acid derivatives, e.g. acid chlorides, acid anhydrides and esters. Esters are prepared by the reaction of carboxylic acids and alcohols. The reaction is acid catalysed and is known as Fischer esterification (see Section 5.5.5). Acid chlorides are obtained from carboxylic acids by the treatment of thionyl chloride (SOCI2) or oxalyl chloride [(COCl)2], and acid anhydrides are produced from two carboxylic acids. A summary of the conversion of carboxylic acid is presented here. All these conversions involve nucleophilic acyl substitutions (see Section 5.5.5). 

Recently, it has been shown that acyl chlorides may be prepared from cyanuric chloride and carboxylic acids (79TL3037). Cyanuric chloride is also valuable for effecting the formation of macrocyclic lactones (Scheme 44) (80TL1893). Similarly, aryl oximes may be converted to... 

From carboxylic acids or acyl derivatives Aluminum chloride, 15 1-Benzotriazolyl diethyl phosphate, 28 Bis(dichloroaluminum)phenylimide,... 

The formation of a-diazoketones from carboxylic acids (via the acyl chloride or an anhydride) and the subsequent Wolff Rearrangement in the presence of nucleophiles results in a one-carbon homologation of carboxylic acids. This reaction sequence. 

When the enolate of an active-methylene compound undergoes acylation with a carboxylic acid chloride, an active-methyne compound is formed initially (Figure 13.65, 13.66). If the electron acceptors therein are solely acyl- or (alkoxycarbonyl) groups, the substructure mentioned suffers from steric hindrance and substantial electrostatic repulsion forces. Active-methyne compounds with such a substitution pattern will react to alleviate this destabilization. 

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