Carboxylic acid chlorides oxalyl chloride

Fig. 6.10. Conversion of carboxylic acids to carboxylic chlorides with thionyl chloride or oxalyl chloride.

Carboxyl groups in diorgano telluriums can be converted to chlorocarbonyl groups by treating the acids with oxalyl chloride at 20°3,4 or with butyl dichloromethyl ether/zinc chloride at 0°. 

The best reagents for converting carboxylic acids to acid chlorides are thionyl chloride (S0C12) and oxalyl chloride [(C0C1)2] because they form gaseous by-products that do not contaminate the product. Oxalyl chloride is particularly easy to use because it boils at 62 °C and any excess is easily evaporated from the reaction mixture. 

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). 

Carboxylic acid chlorides. Conventional methods for conversion of an acid into the acid chloride usually require acidic reagents. Lederle chemists have accomplished this transformation under neutral conditions by conversion of the acid into the t-butyldimethylsilyl ester. The esters react with oxalyl chloride in CH2CI2 in the presence of catalytic quantities of DMF to form the acid chloride with evolution of gas. Since DMF is essential, dimethylformiminium chloride (Vilsmeier reagent) is probably the reactive species. The acid chloride is formed in 85-95% yield, as shown by conversion to esters with ethanol-pyridine. 

For the formation of carboxylic acid chlorides from carboxylic acids different procedures are known. Often thionyl chloride or oxalyl chloride, both with catalytic amounts of DMF, are used. The reaction with thionyl chloride requires elevated temperatures and often provides various byproducts. Oxalyl chloride is useable at room temperature or... 

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. ... 

Preparation of Carboxylic Acid Chlorides. As described in the original article, oxalyl chloride is widely need for the synthesis of carboxylic acid chlorides. This general approach has found use in new chemistry fields such as combinatorial chemistry and dendrimer synthesis. An interesting downstream application was formation of macrocyclic diamides without resorting to high dilution. ... 

Typical procedure. Anthracene 9-carboxylic acid chloride 1341 [1013] A solution of anthracene 1340 (5 g) and oxalyl chloride (30 ml) in nitrobenzene (150 mL) was heated to 120 °C, and then the temperature was raised to 240 °C over a period of... 

Chlorocoumarin may be prepared by the reaction of chromone-2-carboxylic acid with thionyl chloride [169] or oxalyl chloride [55]. 4,4-Dichlorochromen-2-carbonyl chloride which is formed first, reacts with water to give a 91 per cent yield of 4-chlorocoumarin (92) with simultaneous release of carbon monoxide [161]. 

Many procedures for the formation of carboxylic acid amides are known in the literature. The most widely practiced method employs carboxylic acid chlorides as the electrophiles which react with the amine in the presence of an acid scavenger. Despite its wide scope, this protocol suffers from several drawbacks. Most notable are the limited stability of many acid chlorides and the need for hazardous reagents for their preparation (thionyl chloride, oxalyl chloride, phosgene etc.) which release corrosive and volatile by-products. Moreover, almost any other functional group in either reaction partner needs to be protected to ensure chemoselective amide formation.2 The procedure outlined above presents a convenient and catalytic alternative to this standard protocol. 

The Vilsmeier-Haack type adduct, formed by the reaction of oxalyl chloride with DMF can be also be employed for the activation of carboxylic acids, as shown in Fig. 8 [200]. 

The imminium chloride formed was transformed, in-situ, into the corresponding carboxyhc acid derivative, this was added to a solution of cellulose in LiCl/DMAc. Palmitic, stearic, adamantane-1-carboxylic, and 4-nitrobenzoic acids were employed. The DS of the corresponding esters increased as a function of increasing the ratio oxalyl chloride/AGU. The solubihty of the products obtained in aprotic solvents was tested GPC results have indicated negligible degradation of the polymer [200]. 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

The traditional method for transforming carboxylic acids into reactive acylating agents capable of converting alcohols to esters or amines to amides is by formation of the acyl chloride. Molecules devoid of acid-sensitive functional groups can be converted to acyl chlorides with thionyl chloride or phosphorus pentachloride. When milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl chloride provides the acyl chloride. When a salt is used, the reaction solution remains essentially neutral. 

Treatment of carboxylic acids with half an equivalent of oxalyl chloride can generate anhydrides."... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

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