Oxalyl chloride Swern oxidation

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

In Part A geraniol is oxidized to geranial (citral) by Swern s modification of the Moffat oxidation. 1 The stereoisomerlc purity of the product is at least 98%. This procedure is readily conducted on a large-scale and requires only 4 hours time including distillation of oxalyl chloride. The oxidation of geraniol to pure (E)-geranial may also be accomplished by... 

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... 

The conversion of 5 to 6 is a Swern oxidation. The O of DMSO is nucleophilic, and it reacts with oxalyl chloride. Cl- then comes back and displaces O from S to give a S electrophile. The OH of 5 is then deprotonated, whereupon it attacks S, displacing CL. Then deprotonation of a Me group and a retro-hetero-ene reaction occur to give the ketone. 

Oxalyl chloride (98%) was purchased from Aldrich Chemical Company, Inc., and used without further purification. Amounts of reagents for the Swern oxidation have been optimized as reported. Alternative amounts reduce both yield and % ee. 

All of the usual chromium-based oxidation reagents that have been used for the oxidation of cyclobutanols to cyclobutanones, for example, chromium(VI) oxide (Jones reagent),302 pyri-dinium chlorochromate,304 pyridinium dichromate,307 and chromium(YI) oxide/pyridine (Collins),303 are reported to do so without any serious problems. Alternatively, tetrapropylam-monium perruthenate in the presence of A-methylmorpholine A -oxide. oxalyl chloride in the presence of triethylamine in dimethyl sulfoxide (Swern),158,309,310 or phenyl dichlorophos-phate in the presence of triethylamine and dimethyl sulfoxide in dichloromethane (Pfitzner-Moffatt),308 can be used. The Pfitzner-Moffatt oxidation procedure is found to be more convenient than the Swern oxidation procedure, especially with respect to the strict temperature control that is necessary to achieve good yields in the latter, e.g. oxidation of 1 to give 2.308... 

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. 

Triflouroacetic anhydride was used before oxalyl chloride and is also known as the Swern Oxidation. Acetic anhydride can also be used. (Albright-Goldman 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 decomposition of acid-sensitive substrates during Swern oxidations can also be explained by the presence of adventitious hydrogen chloride. This can be avoided by the use of freshly distilled oxalyl chloride and carefully dried DMSO.174... 

As traces of HC1 promoted the decomposition of the starting compound, adventitious HC1 had to be carefully excluded during the Swern oxidation, by using freshly distilled oxalyl chloride and carefully dried DMSO. 

During Swern oxidations, adventitious HC1 may be present either due to the use of impure oxalyl chloride, or due to the hydrolysis of some chlorine-containing chemical, caused by employing wet DMSO. Adventitious HC1 may cause acid-induced side reactions on sensitive substrates.174,246... 

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. 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

In this subsection we want to consider oxidations that employ dimethyl sulfoxide (DMSO) as the oxidizing reagent. These oxidations, which almost always are carried out in the presence of first oxalyl chloride and then NEt3, are referred to as Swern-oxidations. The mechanism of this reaction is known in detail (Figure 17.13). In the prelude, the O atom of DMSO acts as... 

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. 

But the Pfitzner-Moffatt oxidation is not in much use because the Swern oxidation gives better yield and fewer side products. For example, methyl 12-hydroxydodecanoate (7.11) on treatment with DMSO and oxalyl chloride [(COCl)2] in CF12C12 followed by treatment with triethylamine yields 87% methyl 12-oxododecanoate (7.12). 

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. 

The disadvantage of the Swern oxidation is the formation of side products from the Pum-merer rearrangement (see section 1.6.1, Scheme 1.26). To avoid the side reactions in the Swern oxidation, the temperature is kept at -78°C, but when trifluoroacetic anhydride instead of oxalyl chloride is used the reaction can be warmed to -30° C. The use of diisopropylamine as a base stops side reactions. 

Dimethyl snlfoxide-Oxalyl chloride, 8, 200. Swern and co-workers have suggested that the acutal oxidizing agent from DMSO and oxalyl chloride is 1, formed by almost instantaneous loss of CO2 and CO. This is also the reagent obtained by Corey and Kim from dimethyl sulfide and chlorine. (4, 191). 

The prijnary alcohol is oxidi ed in the standai d Swern procedure to give aldehyde 19. This very popuhir oxidation method creates a reactive intermediate (22) from diinethylstilfoxide and oxalyl chloride. This intermediate is then attacked in Sk2 fashion at the sulfur atom by the substrate alcohol, Upon work-up with triethylamiiie the desired aldehyde or ketone and dimethylsulfide is formed. 

Another method of aetivation is known as the Swern oxidation. Under these conditions a reactive dimethylchlorosulfonium chloride is formed from the reaction of dimethyl sulfoxide and oxalyl chloride (Scheme 2.28b). This then reacts with an alcohol to give an alkoxysulfonium salt. In the presence of a base (triethylamine) this salt fragments with the formation of a carbonyl compound (Scheme 2.28c). 

NaHCOs, and methanesulfonic anhydride.Dimethyl sulfoxide in 48% HBr oxidizes benzylic alcohols the aryl aldehydes.Note that Swern oxidation of molecules having alcohol moieties, as well as a disulfide, leads to the ketone without oxidation of the sulfur. Sulfoxides other than DMSO can be used in conjunction with oxalyl chloride for the oxidation of alcohols,including fluorinated sulfoxides and a polymer-bound sulfoxide. ... 

In the first step of the Swern oxidation, DMSO reacts with oxalyl chloride to give an electrophilic chlorosulfonium ion 36, carbon monoxide and carbon dioxide. Ion 36 then reacts with alcohol 37 to give a sulfonium salt 38, which is deprotonated by NEts and then converted to the aldehyde 40 and dimethyl sulfide. 

One example is Swern oxidation, which uses oxalyl chloride and DMSO and is particularly suitable for the selective oxidation of alcohols to aldehydes or ketones. The disadvantages of this oxidation method are the need for low temperatures, the smell of the dimethyl sulfide formed and the possible oxidation of other heteroatoms. Dess-Martin periodinane (DMP, 5) or iodoxybenzoic acid (IBX, 6) are also common oxidizing agents. The main advantage of these two methods is the short reaction time at room temperature. However, typical problems are the low solubility of IBX and the formation of byproducts. In this context, Finney et al. have reported an interesting procedure avoiding these problems by a variation of the temperature IBX is sufficiently soluble in solvents such as ethyl acetate or dichloromethane at elevated temperatures, whereas it is insoluble in these solvents at room temperature. Because of this, the remaining IBX as well as the IBX-derived byproducts can be separated from the reaction mixture by simple filtration. These reisolated IBX byproducts can then be reoxidized and reused. 

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