Activators of dimethyl sulfoxide

Thionyl chloride appears to be siqrerior to trifluoroacetic anhydride as an activator of dimethyl sulfoxide during the oxidation of alcohols in terms of yields of carbonyl compounds, although it has not been as widely used. The active species in this process, leading to an alkoxysulfonium species, is probably the ion pair (26). 

As with trifluoroacetic anhydride, activation of dimethyl sulfoxide with thionyl chloride must be carried out at low temperatures as the reaction is highly exothenmic. Besides the higher yields, a further advantage of thionyl chloride to activate dimethyl sulfoxide over anhydrides is the lack of Pummerer rearrangement products or of esters formed as by-products (as long as Ae reactions are carried out below -60 C). This is amply demonstrated by the oxidation of (-)-bomeol which proceeds in an excellent 99% yield (equation 12). ... 

The above discussion highlights the great synthetic utility of activated dimethyl sulfoxide oxidations in organic chemistry. The enormous amount of effort put into developing these procedures has resulted in a clear picture of their relative value, so enabling one to easily assess the method of chmce for a particular oxidation. The pc ularity of the Swem oxidation reflects the very real advantages that it offers in terms of the mild conditiotts arid hi yields. However, there are many instances where alternative activators of dimethyl sulfoxide are better and it is wise to assess these in any synthetic scheme. 

Ansel HC, Norred WP, Roth IL. Antimicrobial activity of dimethyl sulfoxide against Escherichia coli. Pseudomonas aeruginosa, and Bacillus megaterium. J Pharm Sci 1969 58(7) 836—839. Placencia AM, Oxborrow GS, Danielson JW. Sterility testing of fat emulsions using membrane filtration and dimethyl sulfoxide. ] Pharm Sci 1982 71(6) 704-705. 

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... 

The Swem [vocedure, however, is not without its problems for instance, it has been shown that electrophilic chlorination can occur as a significant side reaction. In these cases the use of trifluoroacetic acetic anhydride as activators of dimethyl sulfoxide has been recommended. 

Mild oxidation of primary and secondary alcohols, promoted by dicyclohexylcarbodiimide activation of dimethyl sulfoxide, evidently involving the alkoxysulfonium ylides, which rearrange intramolecularly to generate aldehydes and ketones, respectively ... 

Activation of dimethyl sulfoxide by oxalyl chloride, as developed by Swern and co-workers [1317-1319,1335,1371-1373], has become the most used of these oxidation procedures, but several of the other methods are also convenient and effi-dent. The usual nudeophiles have been alcohols, phenols, enols, amines, and oximes. 

The present section reviews the recent apphcations in the activation of dimethyl sulfoxide, with the aim of identifying alternative milder and more practical methods for the oxidation of hydroxylic compounds. Thereafter, we focus on oxalyl dichloride, the classical Swem reagent, on diphosgene and triphosgene, as well as on alternative non-chlorine activation methods. 

Acid anhydrides and chlorides are reactive as the electrophile for activation of dimethyl sulfoxide. Preparatively useful procedures based on acetic anhydride/ trifluoroacetic anhydride,and oxalyl chloride have come into general use. The pyridine-SOa complex is also useful.Scheme 10.3 gives some representative examples. Entry 4 is an example of the use of a water-soluble carbodiimide as the activating reagent. The modified carbodiimide facilitates product purification by providing for easy removal of the by-product urea formed from the carbodiimide. 

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

A mixture of the epoxide ca. 5 mmol), sodium azide (6 g, activated by the method of Smith) and 0.25 ml of concentrated sulfuric acid in 70 ml of dimethyl sulfoxide is heated in a flask fitted with a reflux condenser and a drierite tube on a steam bath for 30-40 hr. (Caution carry out reaction in a hood.) The dark reaction mixture is poured into 500 ml of ice water and the product may be filtered, if solid, and washed well with water or extracted with ether and washed with sodium bicarbonate and the water. The crude azido alcohols are usually recrystallized from methanol. 

The use of palladium(II) sulfoxide complexes as catalyst precursors for polymerization has met with mixed results thus a report of a palla-dium(II) chloride-dimethyl sulfoxide system as a catalyst precursor for phenylacetylene polymerization suggests similar results to those obtained using tin chloride as catalyst precursor (421). However, addition of dimethyl sulfoxide to solutions of [NH fPdCh] decreases the activity as a catalyst precursor for the polymerization of butadiene (100). Dimethyl sulfoxide complexes of iron have also been mentioned as catalyst precursors for styrene polymerization (141). 

Tse, G., Orbey, H., and Sandler, S.I. Infinite dilution activity coefficients and Henry s law coefficients of some priority water pollutants determined by a relative gas chromatographic method, Environ. Sci Tecbnol, 25(10) 2017-2022, 1992. Tsierkezos, N.G., Kelarakis, A.E., and Palaiologou, M.M. Densities, viscosities, refractive indices, and surface tensions of dimethyl sulfoxide + butyl acetate mixtures at (293.15, 303.15, and 313.15) K, /. Chem. Eng. Data, 45(2) 395-398, 2000. Tsierkezos, N.G. and Molinou, I.E. Densities and viscosities of ethylene glycol mixtures at 293.15 K, /. Chem. Eng. Data, 44(5) 955-958, 1999. 

IV.C.2. The Active Site of Dimethyl Sulfoxide Reductase (R. sphaeroides and R. capsulatus)... 

Alcohols in which the beta-hydrogen is activated by a double bond undergo dehydration by concentrated alkaline media to produce dienes (49) (Reaction XXXIV). Other products such as ethers are possible when the reaction is done in the presence of dimethyl sulfoxide (50). 

One of the best activators fw dimethyl sulfoxide is the complex of sulfur trioxide/pyiidine, which in the presence of triethylamine rapidly oxidizes primary and secondary alcrdmls to aldehydes and ketones in very good yields at ambient temperature. This reagent also allows the very useM crmversion of allylic alcohols to the corresponding a, unsaturated carbonyl compounds. A further advantage of this procedure over many of the others is the ease of woiit-up, especially over the dimethyl sulfoxide-dicy-clohexylcarbodiimide method. 

In an example of the use of this activation method testosterone, with a IT -hydroxy group, was oxidized to A -androstene-3,17-dione very rapidly in high yield, in contrast to the use DMSO-acetic anhydride. During a reaction, when other oxidizing agents were found to be ineffective, sulfur trioxide/dimethyl sulfoxide led to smooth oxidation of the df-diol (16 equation 8) to an o-quinone in 49% yield and the ci.r-diol (17) to (18 equation 9) in 98% yield. - The use of dimethyl sulfoxide-acetic anhydride for this oxidation gave large amounts of the diacetate as the by-product. 

Undoubtedly the most popular variation of these oxidations is the use of oxalyl chloride to activate the dimethyl sulfoxide, which is commonly referred to as the Swem oxidation. The advantages of the method are the mild conditions the ease of work-up, due to two of the main by-products being carbon monoxide and carbon dioxide the low yields, if any, of Pummerer rearrangement products and the fact... 

One potential activator for dimethyl sulfoxide that in practice turns out to be very poor, is phosgene. However, a related oxidation of alcohols using dimethyl sulfoxide does use phosgene for the preparation of a chloroformate (or carbonochloridate) such as (29). - This reacts with dimethyl sulfoxide to give, after spontaneous loss of carbon dioxide, an alkoxysulfonium salt (30) which upon treatment with tri-ethylamine fonns the carbonyl compound (Scheme 7). Relatively little use appears to have been made of this method. 

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