Alcohols, primary with dimethyl sulfoxide

Primary alkyl halides (chlorides, bromides, and iodides) can be oxidized to aldehydes easily and in good yields with dimethyl sulfoxide.311 Tosyl esters of primary alcohols can be similarly converted to aldehydes,312 and epoxides313 give a-hydroxy ketones or aldehydes.314 The reaction with tosyl esters is an indirect way of oxidizing primary alcohols to aldehydes (9-3). This type of oxidation can also be carried out without isolation of an intermediate ester The alcohol is treated with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC),315 and anhydrous phosphoric acid.316 In this way a primary alcohol can be converted to the aldehyde with no carboxylic acid being produced. 

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. 

Barton devised a new method for the oxidation of primary alcohols to aldehydes involving in the first step conversion to the alkyl chloroformate (1) by adding a solution of the alcohol in ether to ether saturated with phosgene (15-20% w./v.) the solvent is removed at reduced pressure. If the alcohol is hindered, quinoline is added as catalyst and the quinoline hydrochloride removed by filtration. The next step, reaction with dimethyl sulfoxide, is attended with evolution of carbon... 

Pfitzner-Moffatt oxidation. Oxidation of alcohols to carbonyl derivatives with dimethyl sulfoxide and dicyclohexylcarbodiimide. The procedure is especially useful for the conversion of a primary alcohol to an aldehyde without further oxidation to the carboxylic acid. 

Oxidations using dimethyl sulfoxide activated by various reagents began with discoveries by Komblum and co-workers that primary tosylates and certain a-bromo ketones could be converted into aldehydes and glycoxals, respectively, by treatment with dimethyl sulfoxide as the oxidising agent. This was followed by the discovery several years later by Pfitzner and Moffatt that alcohols could be oxidised to carbonyl compounds with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC) and phosphoric acid at room temperature.2 Eventually the method developed by Swern and co-workers, involving activation of dimethyl sulfoxide with oxalyl chloride, came to be the most synthetically useful and widely applied of these mild oxidation procedures.3-6... 

A few years later the Swem laboratory then developed an activator which they claimed to be the most successful in activating dimethyl sulfoxide toward oxidation, namely, oxalyl chloride. Since oxalyl chloride reacted violently and exothermically with dimethyl sulfoxide, successful activation required the use of low temperatures to form the initial intermediate.6 Swem et al. reported the oxidation of long chain primary alcohols to aldehydes which was previously unsuccessful by first converting to the sulfonate ester (either mesylate or tosylate) and then employing the dimethyl sulfoxide-acetic anhydride procedure. They found that long-chain saturated, unsaturated, acetylenic and steroidal alcohols could all be oxidised with dimethyl sulfoxide-oxalyl chloride in high yields under mild conditions. 

A primary alcohol can be oxidized only as far as the aldehyde stage if the alcohol is first treated with tosyl chloride (TsCl) and the resulting tosylate is allowed to react with dimethyl sulfoxide (DMSO). Propose a mechanism for this reaction. Hint See Section 20.2.)... 

Swern oxidation of a primary alcohol with dimethyl sulfoxide, oxalyl chloride, and triethylamine (11.5). 

Saturated Aldehydes and Ketones - Both primary and secondary alcohols can be oxidized in 94-98% yield to their corresponding carbonyl compounds with dimethyl sulfoxide-chlorine complex at -45 to -10 , a procedure which Is reportedly superior to previous oxidation methods. Terminal alkynes are converted to ketones by alkylation or protonation of their lithium alkynyltrlalkylborate salts, followed by H2O2 oxidation. 

The reaction is of the 8 2 type and works best with primary and secondary alkyl halides Elimination is the only reaction observed with tertiary alkyl halides Aryl and vinyl halides do not react Dimethyl sulfoxide is the preferred solvent for this reaction but alcohols and water-alcohol mixtures have also been used... 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Dimethyl sulfoxide reacts with trifluoroacetic anhydride at low tempera ture to give a complex that is an efficient reagent for the oxidation of alcohols to carbonyl compounds [40 41] This reagent can be used to oxidize primary and secondary aliphatic alcohols, cycloalkyl alcohols, and allylic, homoallylic, ben-zylic, acetylenic, and steroidal alcohols (equation 19)... 

The starting compound 251 was reduced to 252 with sodium borohydride. The latter was heated under reflux in 6% sulfuric acid in methanol to afford compound 253. Treatment of the latter with maleic anhydride at 170° for 3 hr afforded compound 254. Bisdecarboxylation of 254 with dicarbonyl bistriphenylphosphinenickel in anhydrous diglyme under nitrogen at reflux temperature for 6 hr afforded the olefin 255 in 69% yield (171). The latter was reduced with lithium aluminium hydride to the primary alcohol 256, which was oxidized to the aldehyde 257 with Ar,A -dicyclohexylcarbodiimide, dimethyl sulfoxide and pyridine in dry benzene. Treatment of the aldehyde 257 with an excess of the Grignard reagent prepared from l-bromo-3-benzyloxybutane afforded a mixture of diastereoisomers represented by the structure 258. 

Alternatively it is possible to oxidize a primary alcohol no further than to give the aldehyde. This is the domain of the Collins reagent, PCC, PDC, or activated dimethyl sulfoxide. The oxidation of primary alcohols with K2Cr207 in aqueous solution to nothing but the aldehyde, (i.e., without further oxidation to the carboxylic acid) is possible only if a volatile aldehyde results and is distilled off as it is formed. This is the only way to prevent the further oxidation of the aldehyde in the (aqueous) reaction mixture. Selective oxidations of primary alcohols to aldehydes with the Jones reagent succeed only for allylic and benzylic alcohols. Otherwise, the Jones reagent directly converts alcohols into carboxylic acids (see above). 

Dimethyl sulfoxide and chlorine form highly reactive intermediates which are of some limited use as oxidants for alcohols. These intermediates are related to those derived from the reaction of the halogens with dimethyl sulfide and probably have a structure such as (27). When formed at -4S C they allow the oxidation of primary and secondary alcdiols to aldehydes and ketones when used in a two-fold excess. For very simple alcdiols the reaction proceeds in yields of greater than 90%, but there are considerable drawbacks if some types of additional functionality are present in the molecule, e.g. alkenes react very rapidly to form vicinal dichlorides. 

Oxidation of alkyl 4-nitrobenzenesulfonates. The oxidation of primary alcohols to aldehydes by dimethyl sulfoxide requires temperatures around 100° or introduction of acids or heavy metal ions. In a new procedure the alcohol is converted into the 4-nitrobcnzenesulfonate ester by reaction with 4-nitrobenzenesulfonyl chloride and... 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

In the first step of this reaction sequence, the primary alcohol 21 is oxidized to the corresponding aldehyde 38 in a Parikh-Doering oxidation which is related to the Swern oxidation. In general, this type of oxidation is conveniently carried out by addition of a solution of pyridine-SOs complex in DMSO to a mixture of the alcohol, DMSO and NEts. It can be assumed that dimethyl sulfoxide and sulfur trioxide react to form 0-dimethylsulfoxonium sulfate 40, which then further reacts with primary alcohol 39 to give 0-alkyl dimethylsulf-oxonium intermediate 41. Then, sulfonium salt 42 is formed and subsequently deprotonated by NEts to give sulfonium ylide 43. Finally, an intramolecular p-elimination occurs to provide the desired aldehyde 44 and dimethyl sulfide. 

Displacements. Primary and secondary alkyl chlorides react rapidly and exother-mally with sodium cyanide in partial solution in dimethyl sulfoxide to give the corresponding nitriles in excellent yield. - The reactions are faster and the yields better than in the reactions of the corresponding bromides or iodides in aqueous alcohol. Neopentyl and neophyl halides can be converted by this method to... 

Dimethyl sulfoxide-Sulfur trioxide [1, 309, before references]. The combination of DMSO and sulfur trioxide, in the form of the pyridine complex, in the presence of trimethylamine oxidizes primary and secondary alcohols in good yield to aldehydes and ketones, respectively.55 The reaction usually is complete within minutes and the products are isolated by acidification and precipitation with water. The reagent also oxidizes allylic alcohols to the corresponding a,fi-unsaturated carbonyl compounds. One advantage over the DMSO-DCC method is that the elaborate purification required when dicyclohexylurea is a product can be dispensed with. Testosterone, with a 17/3-hydroxyl group, was oxidized toA -androstene-3,17-dione very rapidly the 17-epimer required a period of 35 min. 

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