Oxalyl chloride alcohol oxidation

The oxidation of primary or secondary alcohols to aldehydes or ketones respectively with dimethyl sulphoxide activated by oxalyl chloride has wide applicability (Swern oxidation).243b The initial reaction between the acid chloride and dimethyl sulphoxide in dichloromethane solvent is vigorous and exothermic at — 60 °C and results in the formation of the complex (7) this complex spontaneously decomposes, even at this low temperature, releasing carbon dioxide and carbon monoxide to form the complex (8). The alcohol is added within 5 minutes, followed after 15 minutes by triethylamine. After a further 5 minutes at low temperature the reaction mixture is allowed to warm to room temperature and work-up follows standard procedures. The ratio of reactants is dimethyl sulphoxide oxalyl chloride alcohol triethylamine 2.2 1.1 1.0 5. 

In more recent works, the use of dicyclohexylcarbodiimide has been abandoned because the reaction works satisfactorily with acid catalysts alone, followed by bases such as triethylamine or diisopropylethylamine, which gives, sometimes, even better yields than triethylamine [1012,1023. Several activators are being used, and the best seems to be oxalyl chloride (theSwern oxidation) [1023,1149]. Other activators are mentioned in the section Oxidation of Primary Alcohols to Aldehydes. The advantages of oxidations with dimethyl sulfoxide lie in the mildness of the reagent and in the low temperatures, sometimes -45 °C [1020] or -60 °C [1023], at which the reactions are run. 

Oxidation of an Alcohol with Dimethyl Sulfoxide —Oxalyl Chloride (Swern Oxidation)... 

In order to enable the dimethyl sulfoxide 3 to oxidize the alcohol substrate effectively, it has to be converted into an reactive agent. This is carried out by treatment with oxalyl chloride 4, hence leading to sulfonium ions 5 or 6 as the active species ... 

Reaction of (S)-(+)-2-aminobutyrate hydrochloride with ethyl oxalyl chloride followed by replacing of the ethyl ester with amino alcohol, oxidation with Dess-Martin periodinate and cyclization using TFA/TFAA in acetic acid gave the cyclic product, which was further converted to the bromide. Sub-... 

Whereas the original Moffat-Pfitzner oxidation employs dicyclohexylcarbodiimide to convert DMSO into the reactive intermediate DMSO species 1297, which oxidizes primary or secondary alcohols via 1298 and 1299 to the carbonyl compounds and dicyclohexylurea [78-80], subsequent versions of the Moffat-Pfitzner oxidation used other reagents such as S03/pyridine [80a, 83] or oxalyl chloride [81-83] to avoid the formation of dicyclohexylurea, which is often difficult to remove. The so-called Swern oxidation, a version of the Moffat-Pfitzner oxidation employing DMSO/oxalyl chloride at -60°C in CH2CI2 and generating Me2SCl2 1277 with formation of CO/CO2, has become a standard reaction in preparative organic chemistry (Scheme 8.31). 

Several laboratories have reported that Swern oxidation of alcohols can be accompanied of a-chlorination of keto or (1-keto ester groups. Undesired electrophilic chlorination can be avoided by use of oxalyl chloride (1.05 equiv.) and DMSO (2.5 equiv.) in stoichiometric amounts or by use of acetic anhydride or trifluoroacetic anhydride in place of oxalyl chloride.1... 

Oxidation of alcohols.1 This phosphate is apparently as efficient as oxalyl chloride for activation of DMSO for oxidation, and the derived reagent is less prone to give chlorine-containing byproducts. The reactions are rapid at 20° or below, and yields are generally 75-95%. 

A very useful group of procedures for oxidation of alcohols to ketones have been developed which involve DMSO and any one of several electrophilic reagents, such as dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, or... 

Similar oxidation of alcohols has been carried out with dimethyl sulfoxide and other reagents317 in place of DCC acetic anhydride,318 SOy-pyridine-triethylamine,319 trifluo-roacetic anhydride,320 oxalyl chloride,321 tosyl chloride,322 chlorine,323 bromine,324 AgBF4-Et3N,325 P205-Et3N,326 phenyl dichlorophosphate,327 trichloromethyl chloroformate,328 tri-... 

Swern oxidations have been performed using the PEG2000 bound sulfoxide 34 as a dimethylsulfoxide (DMSO) substitute (reaction 13).49-50 Several alcohols were efficiently oxidized to their aldehydes or ketones using this reagent, oxalyl chloride, and triethylamine. Precipitation of the polymer with cold diethyl ether and filtration through a pad of silica afforded the desired oxidized products in very good yields and purities. The reduced sulfide polymer could be reoxidized to sulfoxide 34 with sodium metaperiodate and used again in reactions with no appreciable loss in oxidation capacity. 

Sulfur trioxide is one of many reagents [e.g.. DCC Ac20, (COC1) TPAA with which DMSO can be activated as an oxidizing reagent lor alcohols. Oxalyl chloride has found the widest application in the reaction named after Swem.Xi Structure 43 represents the activated species in the above oxidation. 

Few oxidation methods have enjoyed the almost immediate success of the Swern procedure for the oxidation of alcohols. Since the publication of three foundational papers161 in 1978-79, Swern has become the de facto oxidation method by default whenever activated DMSO is desired. It offers the advantage of quite consistent good yields in many substrates, with an operation performed under very low temperature and mild conditions. Swern s procedure consists of the oxidation of an alcohol using DMSO, activated by reaction with oxalyl chloride. According to Swern, oxalyl chloride is the most effective activator of DMSO examined by his group.162 It must be mentioned that Swern s research team is probably the one that has tried the highest number of DMSO activators for the oxidation of alcohols. 

The acid 350 was demethylated with pyridine hydrochloride, then realkylated with benzyl bromide in aqueous potassium hydroxide to give 351. The latter was converted to the diazoketone 352 by the sequential treatment of 351 with oxalyl chloride and etheral diazomethane. Reaction of 352 with concentrated hydrobromic acid gave the bromoketone 353. The latter was reduced with sodium borohydride at pH 8 -9 to yield a mixture of diastere-omeric bromohydrins 354. Protection of the free hydroxyl as a tetrahydro-pyranyl ether and hydrogenolysis of the benzyl residue afforded 355. The phenol 355 was heated under reflux with potassium m/V-butoxide in tert-butyl alcohol for 5 hr to give a 3 1 epimeric mixture of dienone ethers 356 and 357 in about 50% yield. Treatment of this mixture with dilute acid gave the epimeric alcohols 358 and 359. This mixture was oxidized with Jones reagent to afford the diketone 349. 

A related radical transformation can be used to prepare 2,2-disubstituted selenanes. Treatment of the alcohol 124 with oxalyl chloride followed by addition of 2-mercaptopyridine iV-oxide and heating afforded the selenane 125 in moderate yield (Scheme 11) <2001JOC6286>. The required alcohol precursor for this reaction can be readily prepared from the bromo ester and in ////-generated sodium benzyl selenide, followed by Grignard addition. 

Aminothiazole, with acetaldehyde, 42 to 2-mercaptothiazoie, 370 4-Aminothiazole-2,5-diphenyl, to 2,5 di-phenyl-A-2-thiazoline-4-one, 421 Ammothiazoie-A -oxide, 118 2-Aminothiazoles. 12 acidity of, 90 and acrylophenone, 42 acylations of, with acetic acid. 53 with acetic anhydride, 52 with acyl halides, 48 with chloracetyl chloride, 49 with-y-chlorobutyrylchloride, 50 with 0-chloropropionylchloride, 50 with esters, 53 with ethy acrylate, 54 with indoiyl derivatives, 48 with malonic esters, 55 with malonyl chloride, 49 with oxalyl chloride, 50 with sodium acetate, 52 with unsaturated acyl chloride, 49 additions to double bonds, 40 with aldehydes, 98 alkylations, with alcohols, 38 with benzyhydryl chloride, 34 with benzyl chloride, 80 with chloracetic acid, 33 with chloracetic esters, 33 with 2-chloropropionic acid, 32 with dialkylaminoalkyl halides, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38... 

The Swern oxidation uses dimethyl sulfoxide (DMSO) as the oxidizing agent to convert alcohols to ketones and aldehydes. DMSO and oxalyl chloride are added to the alcohol at low temperature, followed by a hindered base such as triethylamine. The reactive species (CH3)2SC1, formed in the solution, is thought to act as the oxidant in the Swem oxidation. Secondary alcohols are oxidized to ketones, and primary alcohols are oxidized only as far as the aldehyde. The by-products of this reaction are all volatile and are easily separated from the organic products. 

A mild oxidation, using DMSO and oxalyl chloride, that can oxidize primary alcohols to aldehydes and secondary alcohols to ketones, (p. 472)... 

In the Swern oxidation, the reaction of oxalyl chloride with DMSO may generate chlorodimethylsulfonium chloride (A), which reacts with the alcohol to give alkoxysulfonium ion intermediate B. The base, typically triethylamine, deprotonates the alkoxysulfonium ion B to give the sulfur ylide C, which decomposes to give DMS and the desired aldehyde or ketone (Scheme 7.7). The temperature of this reaction is kept near —60 to -78°C. 

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