Swern oxidation solvent

This fluorine-containing, oxidation-resistant alcohol is best oxidized by the Pfitzner-Moffatt reaction, using dichloroacetic acid as catalyst. Observe the use of toluene, instead of carcinogenic benzene, as solvent. A Swern oxidation was not reproducible, and caused substantial epimerization of the isobutyl side chain. Collins oxidation was successful, but ... 

Most Omura-Sharma-Swern oxidations are performed in CH2CI2, although other apolar solvents, like toluene,125 can be equally effective. 

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 simplest sulphoxide, dimethyl sulphoxide, is an important aprotic solvent (Section 4.1.55, p. 412). Its use as a reagent in carbon-carbon forming reactions and as a reagent for the oxidation of alcohols to carbonyl compounds (p. 608) (the Pfitzner-Moffatt and Swern oxidations) has been extensively reviewed.244 An illustrative example of carbon-carbon bond formation using dimethyl sulphoxide is noted in Expt 7.3. 

TMS ethers of primary alcohols and most secondary alcohols do not survive even the simplest synthetic manipulations — especially if protic solvents are involved. For example, Swern oxidation or Collins oxidation conditions will cleave a primary TMS ether and perform the oxidation in the presence of a secondary TMS ether.3 Owing to the sensitivity of TMS ethers., deprotection can usually be achieved under very mild conditions (e,g., acetic acid or potassium carbonate in methanol). The rate of hydrolysis depends on both steric and electronic effects with hindered environments decreasing the rate and electron-withdrawing substituents on the hydroxyl function increasing the rate. In a synthesis of Zaragozic Acid A. the... 

Silver salts are also utilized to perform nucleophilic additions to disulfide bonds to yield sulfenamides (146). If alkyl halides are treated with stoichiometric AgBF4 in dimethyl sulfoxide solvent (DMSO, solvent), the corresponding aldehydes/ ketones will form in good yields. This reaction is an alternative to the well-known Swern oxidation (147). In addition, silver can drive the formation of dialkylper-oxonium ions from alkyl halides, which then oxidizes sulfoxides or sulfides (148,149). In the presence of AgN03, sulfides can be oxidized into a-chloro sulfoxides by SO2CI2 (Fig. 36) (150). 

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. 

Adding reagents at low temperatures can create problems if the freezing point of the reagent is above the temperature of the reaction. For instance, oxalyl chloride (mp —10 to — 8°C) is often used for Swern oxidations of secondary alcohols. Typically this reaction is conducted at —78 to — 70°C, and oxalyl chloride is added to the surface of the reaction. Under these conditions oxalyl chloride may freeze at the point it exits the addition line. Diluting with solvents allows compounds with relatively high freezing points to be added to cold reactions. 

More generally, the procedure described in step C illustrates how the Swern oxidation method can be employed for the selective oxidation of an alcohol functionality in the presence of a sulfur moiety. A drawback of the original Swern oxidation is the lack of solubility of some substrates in the dichloromethane solvent at low temperatures, which results in a serious reduction of yield. In the past this has been avoided by carrying out the oxidation step at -10°C. This once again gave excellent yields, but this procedure required the use of twice the stoichiometric amount of oxidant. The method described here as step C demonstrates that this is not necessary, and that the oxidation of insoluble materials can be carried out following the routine procedure provided that the substrate is added as a solution in dry dimethyl sulfoxide. 

The trialdehyde 38 was obtained in four steps in 60-65% overall yield from trimesic acid (34, Scheme 3). Esterification of 34 with 1-propanol in excess, by refluxing with hydrogen chloride catalyst, leads to triester 35 in quantitative yield. Hydrogenation of 35 in acetic acid solvent (Pt catalyst) yields pure cij,ds-cyclohexane-l,3,5-tricarboxylate ester 36, also in quantitative yield. Reduction of ester 36 with lithium aluminum hydri in tetrahydrofuran solvent produces c ,cis-l,3,5-tris(hydroxymethyl)cyclo-hexane cis,cis-37) in 90-95% yields. Swern oxidation of triol 37 led to cij,c -l,3,5-triformylcyclohexane 38 in 70% yield. The stereochemistry of 38, as well as that of precursors 36 and 37, was established as ca,cis in each case by high resolution H NMR. 

Startg. dialdehyde (prepared by Swern oxidation of the corresponding diol) in methylene chloride treated with gaseous NH3, solvent removed, the residue taken up in acetic acid, and the resulting soln. heated at 70° for 1.5 h product. Y 77%. R.B. Ruggeri et al., J. Am. Chem. Soc. 110, 8734-6 (1988). 

This is a good point to introduce some of the organic applications of higher-valent sulfur compounds. Dimethyl sulfoxide (DMSO) is well known in this regard it is not only an important polar, aprotic solvent but is also used to oxidize primary and secondary alcohols to the corresponding carbonyl compounds in a number of synthetic reactions, of which the Swern oxidation is the most important. The reagents used in the Swern oxidation are DMSO, oxalyl chloride, and an organic base such as triethylamine ... 

In the search for specific and gentle oxidizing agents for alcohols that leave other functional groups unaffected, it has been found that reduction of the common solvent, methylsulfinylmethane (dimethyl sulfoxide [DMSO] [( 3)280]) to dimethyl sulfide can be very useful. Thus, both items 6 and 7 in Table 8.5, the MofEatt oxidation and the Swern oxidation, respectively, which can be performed with exquisite selectivity at low to moderate temperatures, have found wide use. 

Additionally, it must be mentioned that the formation of methylthio-methyl ethers in oxidations with activated DMSO is minimized by the use of solvents of low polarity.123 Hence, the routine use of CH2CI2—which possesses a good balance of solubilizing power versus low polarity—is practiced in Omura-Sharma-Swern and MofTatt oxidations. The formation of side compounds—both trifluoroacetates and methylthiomethyl ethers—is decreased by using more diluted reaction conditions under Procedure C, while concentration has little effect on the yield in oxidations performed under Procedure A.124... 

The oxidation of alcohols to carbonyl compounds is one of the most fundamental and important processes in the fine chemical industry. The classical methodology is based on the stoichiometric use of heavy metals, notably Cr and Mn (1,2). Alternatively metal-free oxidation, such as the Swern and Pfitzner-Moffat protocols, is based on e.g., dimethylsulfoxide as oxidant in the presence of an activating reagent such as N,N -dicyclohexylcarbodiimide, an acid anhydride or acid halide (3). Although the latter methods avoid the use of heavy metals, they usually involve moisture-sensitive oxidants and environmentally undesirable reaction media, such as chlorinated solvents. The desired oxidation of alcohols only requires the formal transfer of two hydrogen atoms, and therefore the atom economy of these methods is extremely disadvantageous. The current state of the art in alcohol oxidations... 

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