Oxalyl Chloride

[79-37-8]  · C2Cl2O2  · Oxalyl Chloride  · (MW 126.92)

(versatile agent for preparation of carboxylic acid chlorides;1 phosphonic acid dichlorides;2 alkyl chlorides;3 b-chloro enones;4 acyl isocyanates5)

Physical Data: mp -12 °C; bp 63-64 °C/763 mmHg; d 1.48 g cm-3; n20D 1.4305.

Solubility: sol hexane, benzene, diethyl ether, halogenated solvents, e.g. dichloromethane and chloroform, acetonitrile.

Form Supplied in: colorless, fuming liquid; widely available; 2M soln in dichloromethane.

Handling, Storage, and Precautions: liquid and solution are toxic, corrosive, and severely irritating to the eyes, skin, and respiratory tract. Use in a fume hood and wear protective gloves, goggles, and clothing. Bottles should be stored in a cool, dry place and kept tightly sealed to preclude contact with moisture. Decomposes violently with water, giving toxic fumes of CO, CO2, HCl.

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.1 Acid chlorides produced by this means have subsequently featured in the synthesis of acyl azides,6 bromoalkenes,7 carboxamides,8 cinnolines,9 diazo ketones,10 (thio)esters,11 lactones,12 ketenes for cycloaddition reactions,13 intramolecular Friedel-Crafts acylation reactions,14 and the synthesis of pyridyl thioethers.11

Like Thionyl Chloride, oxalyl chloride gives gaseous byproducts with acids and the chlorides can be readily isolated in a pure form by evaporation of the solvent and any excess reagent, or used in situ for further elaboration (eq 1).

Prior formation of an amine or alkali metal salt, with or without pyridine,1 has been used to advantage with substrates that are sensitive to strong acids or are bases (see also Oxalyl Chloride-Dimethylformamide for a procedure conducted under neutral conditions using silyl esters). By adjusting the molar proportions of oxalyl chloride to substrate, anhydrides can also be prepared using these methods (eq 2).15 N-Carboxy-a-amino acid anhydrides can also be made this way.16

The use of nonpolar solvents such as hexane or toluene allows for the removal of inorganic or amine salts which may otherwise interfere with subsequent reactions.

Under the mild conditions employed (eqs 3 and 4),17 racemization of stereogenic centers, skeletal rearrangement, or byproduct formation, seen with other reagents such as thionyl chloride/pyridine,18 are seldom observed.

Conversion of b-bromoacrylic acid to the acid chloride using thionyl chloride/DMF, Phosphorus(III) Chloride, or benzotrichloride/zinc chloride also resulted in bromine for chlorine exchange. Use of oxalyl chloride with the preformed ammonium salt provided a mild, general method to b-bromoacryloyl chlorides (eq 5)19 without halogen exchange or (E/Z) equilibration. b-Fluoro- and iodoacrylic acids have been cleanly converted to the acid chlorides without prior salt formation.

As well as forming acid chlorides, a-tertiary amino acids can react with oxalyl chloride and undergo an oxidative decarboxylation to give iminium salts, or ring expansion, depending on the substituents and their stereochemistry (eq 6).20

Preparation of Phosphonic Acid Chlorides.

Phosphonic acid dichlorides have been obtained in high yield (determined by 31P NMR) at low temperature from the corresponding acids using oxalyl chloride and Pyridine (eq 7).2

Similarly, monoalkyl methylphosphonochloridates (eq 8)21 can be made from dialkyl esters; thionate acid chlorides could not be made by this method. Thionyl chloride and PCl5 were also used to make this type of compound (see also Oxalyl Chloride-Dimethylformamide).

Numerous other reagents such as PCl3, PCl5, POCl3, and Ph3P/CCl4 are available for the preparation of acid chlorides and anhydrides but may not be as convenient as the byproducts are not so easily removed, or the reactions require more vigorous conditions.

Direct Introduction of the Chlorocarbonyl Group (Halocarbonylation).

Alkanes or cycloalkanes react with oxalyl chloride under radical conditions; typically, mixtures are produced.22 However, bicyclo[2.2.1]heptane undergoes regio- and stereospecific chlorocarbonylation, giving the ester on subsequent methanolysis (eq 9).23

Certain alkenes such as 1-methylcyclohexene and styrene react with oxalyl chloride, under ionic conditions without added catalyst, to give alkenoic acid chlorides in variable yields. Alkenes such as octene and stilbene did not react under these conditions.24

Reactions of aromatic compounds with oxalyl chloride/Lewis acid catalysts have been reviewed.25 Anthracene is unusual as it undergoes substitution without added catalyst (eq 10).26

Preparation of Chloroalkanes.

Alcohols react with oxalyl chloride to give oxalyl monoalkyl esters, which if heated in the presence of pyridine give the alkyl chloride (eq 11).3

Tertiary alcohols have been converted to tertiary chlorides in a Barton-Hunsdiecker type radical process using hydroxamate esters (eq 12).27

Chlorination of Alkenes.

A novel stereospecific dichlorination of electron rich alkenes has been reported using a manganese reagent generated from Benzyltriethylammonium Chloride and oxalyl chloride (eqs 13-17).28 No oxygenation byproducts are observed.

Reactions with Carbonyl Groups.

Unsaturated 3-keto steroids give the corresponding 3-chloro derivatives with oxalyl chloride (eq 18).4 Prolonged heating can give rise to aromatization.4 Tropone gives the chlorotropylium chloride in high yield.4 In a related reaction, 1,2-dithiol-3-ones and -3-thiones give dithiolium salts when heated in toluene or chloroform with the reagent.4 A range of b-chloro enones has been prepared from diketones. Dimedone gives the b-chloro enone in high yield (eq 19).29 Keto esters did not react to give b-chloro esters.

b-Keto aldehydes give a single regio- and stereospecific isomer, the chlorine being cis to the carbonyl group (eq 20).

Certain triketones give 3-chlorides with excess oxalyl chloride, in good yield (eq 21).30

Preparation of Acyl Isocyanates and Aryl Isocyanates.

Certain primary carboxamides can be converted to acyl isocyanates in yields from 36-97% with the reagent (eq 22);5 Phosgene gives nitriles under similar conditions. Oxalyl chloride has found limited application for the preparation of triazine and quinone isocyanates.5

Miscellaneous Applications.

Oxalyl chloride has been used in the preparation of 2,3-furandiones from alkenyloxysilanes,31 o-aminophenols from N-aryl nitrones,32 dihydroquinolines via a modified Bischler-Napieralski ring closure,33 2,3-b-furoquinoxalines from quinoxazolones,34 sterically hindered salicylaldehydes from phenoxyoxalyl chlorides,35 and in mild cleavage of 7-carboxamido groups in cephalosporin natural products, without cleavage of the lactam ring or disruption of optical centers.36

Related Reagents.

Dimethyl Sulfoxide-Oxalyl Chloride; Oxalyl Chloride-Aluminum Chloride.

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Roger Salmon

Zeneca Agrochemicals, Bracknell, UK

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