Synthesis of Acid Chlorides

1 hope that these problems convince you that these displacements are essentially all the same mechanistically and give you the confidence to tackle less familiar examples. 

FIGURE 15.30 Mechanism of acid chloride synthesis using thionyl chloride. 

FIGURE 15.32 Preparation and use in synthesis of acid chiorides using oxalyl chloride. 

FIGURE 15.33 Formation of acid chlorides using PCI5 

The first step of the reaction is the displacement of chloride from PCI5 by the acid. The displaced chloride will then attack the carbonyl, expelling 013 = O and chloride  

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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). 

Synthesis of Acid Chlorides Acid chlorides (acyl chlorides) are synthesized from the corresponding carboxylic acids using a variety of reagents. Thionyl chloride (SOCl2) and oxalyl chloride (COCl)2 are the most convenient reagents because they produce only gaseous side products (Section 20-15). 

Most of the conventional reagents for the synthesis of acid chlorides from carboxylic acids are unsatisfactory for the preparation of a-keto acid chlorides. For example, the reaction of pyruvic acid with phosphorus halides does not give pyruvoyl chloride7 whereas the use of phosgene8 or oxalyl chloride9,10 affords ether solutions of the acid chloride in low yield. Recently a useful preparation of pyruvoyl chloride from trimeth-ylsilyl pyruvate and oxalyl chloride has been described.11... 

The most widely used synthesis of acid chlorides is based on the reaction of a free carboxylic acid with thionyl chloride. A number of examples of this reaction can be found. The mechanism seems to involve an intermediate chloro sulfite, which is transformed to the acid chloride (equation 1). Polar solvents normally increase the reaction rates. ... 

Despite their simplicity, neither of these routes have been developed commercially. However, the use of phosgene with carboxylic acids to form acid chlorides has many advantages over the use of PCI 5 or SOClj, in that the by-products (COj and HCI) are readily removed, leaving a high purity product this is especially important in the synthesis of acid chlorides of fatty acids, which resist distiliation [1841a]. Isophthaloyl dichloride and terephthaloyl dichloride are both produced commercially by the action of phosgene on their respective acids [1804a]. 

Write equations representing the synthesis of acid chlorides. 

Writing Equations Representing the Synthesis of Acid Chlorides... 

A procedure using silyl esters, developed to allow synthesis of acid chlorides under neutral conditions, has been applied to a range of substrates (eq 5), including amino acid anhydrides. ... 

Methods are indicated for producing esters directly from the acid chlorides in this case the reaction is conducted in a solvent (for example, in nitrobenzene) or without it [68, 69]. However, the synthesis of acid chlorides containing substituents with labile hydrogen atoms in the ortho-position to the carboxyl group involve definite difficulties. Protection of the OH group in salicylic acid, for example, by methoxyla-tion, followed by its saponification, complicates the technology and leads to considerable losses of the finished product. 

Quesnel and Arndtsen reported a palladium-catalyzed carbonylation approach to the synthesis of acid chlorides. As an extension of this methodology, it was found that indoles, carbazoles, and anilines could be N-carbonylated at room temperature from simple aryl iodides and carbon monoxide in good yields (229- 230) (13JA16841). 

PROBLEM 17.19 Another excellent synthesis of acid chlorides from carboxylic adds uses either phosgene (Cl—CO—Cl) or oxalyl chloride (Cl—CO—CO—Cl) as the reactive agent. Suggest a mechanism for the reaction with phosgene. 

In addition to its use in the synthesis of acid chlorides, polymeric phosphine dichloride also converts alcohols to the corresponding chloride. 

A mild method for the synthesis of acid chlorides has been described which involves the reaction of a trichloromethyl-arene (98) with an organosilicon oxide, resulting in the formation of the aa-dichlorobenzyloxytrimethylsilane (99). This undergoes /S-elimination of trimethylchlorosilane (Scheme 13), which can be hydrolysed to hexamethyldisiloxane and re-used. 

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