Alcohols with dimethyl-sulphoxide

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. 

Equimolar quantities of benzhydrol and the phosphorane (3a) were also reacted in dimethyl sulphoxide solution. Apart from bis(benzhydryl) ether (18%) and catechol monobenzhydryl ether (39%), a small amount of benzophenone (17%) was obtained. It was shown that, in the absence of phosphorane, benzhydrol is not oxidised to benzophenone by dimethyl sulphoxide. Reaction similar to that outlined in Scheme 1 is a likely possibility. Again, the alcohol is activated by reaction with the phosphorane toward nucleophilic attack, in this case by dimethyl sulphoxide. Significantly, oxidation of alcohols by dimethyl sulphoxide is usually carried out using the Pfitzner-Moffatt reagent (dicyclohexyl carbodiimide and anhydrous phosphoric acid in dimethyl sulphoxide) (13) whereas the reaction using the phosphorane (3a) is carried out under neutral conditions. Unfortunately, however, attempts to improve the yield of benzophenone have hitherto failed. 

Hoffman-La Roche s contribution to the design of semi-synthetic y5-lactamase inhibitors was the synthesis of 6-(Z)-acetylmethylenepenicillanic acid (Ro 15-1903) (27) from the 6-a-hydroxypenicillanate ester (52) Scheme 6.9) [73]. Oxidation of alcohol (52) with dimethyl sulphoxide-trifluoroacetic anhydride gave the ketone (53) which in turn reacted with l-triphenylphosphoranylidene-2-propanone to yield the (Z)-isomer (54) of the acetonylidenepenicillanate as the major product. Deprotection then provided 6-acetylmethylenepenicillanic acid (27). 

The oxidation of midecamycin with dimethyl sulphoxide-acetic anhydride has been studied the macrolide allylic alcohol function was oxidized to the corresponding ketone, whereas the 2 -hydroxy-group on the mycaminose moiety was acetylated rather than oxidized, while the mycarose unit was simultaneously converted to its 3"-0-methylthiomethyl ether derivative. ... 

Ion exchange resins have occasionally been used to adsorb fiavones from aqueous solutions they can then be eluted with alcohol. Weakly polar substances have been separated by partition chromatography on silica gel, impregnated with dimethyl sulphoxide [156] benzene was used as solvent. An interesting separation is that of betacyanins with an aqueous potassium acetate solution on polyamide [198]. 

The condensation reaction is promoted by certain polar solvents and of the many which have been tested dimethyl sulphoxide appears to be the most effective. As usual with linear condensation polymers molecular equivalence and near-absence of monofunctional material is necessary to ensure a high molecular weight. Moisture and alcohols can also have a devastating effect on the molecular weight. In the case of water it is believed that 4-chlorophenyl 4-hydroxyphenyl sulphone is formed which functions as an effective chain terminator. Gross contamination with air is also believed to reduce the maximum attainable molecular weight as well as causing intense discolouration. 

Shatenshtein et al.5 5 5- 591 have also measured rate coefficients for dedeuteration of thiophen derivatives by lithium or potassium l-butoxides in dimethyl sulphoxide or l-butyl alcohol (70 vol. %) in diglyme (Table 178). Interestingly, the 2 position is more reactive than the 3 position and this was reasonably attributed to the —I effect of the hetero sulphur atom. The methyl substituent lowers the reactivity of the 2 position from each position in accord with its +1 effect and consequently the effect was greatest from the 3 position. However, the deactivation from the 5 position was greater than from the 4 position, and this was incorrectly attributed to the +M effect of methyl group operating from the 5 position since... 

Another marked physical difference between sulphides and sulphoxides (or sulphones) is that sulphoxides (and lower alkyl sulphones) are hygroscopic and dissolve quite readily in water or protic solvents such as alcohols, and even more so lower alkyl or alkyl aryl sulphoxides are almost freely miscible with water. This can be accounted for by the formation of the strong hydrogen bond between the S—O bond in the sulphoxides and water molecules. Moreover, lower alkyl sulphoxides and sulphones such as dimethyl sulphoxide (DMSO) or sulpholene can dissolve a number of metallic salts, especially those of alkali and alkaline earth metals, and hence these compounds have been widely utilized as versatile and convenient solvents in modern organic chemistry26 (Table 3). 

Dihydrodithiin sulphoxides, synthesis of 243 Dihydrothiophene dioxides, reactions of 653 /(,/( -Dihydroxyketones 619 Dimerization, photochemical 877, 884 Dimethyl sulphoxide anion of - see Dimsyl anion hydrogen bonding with alcohols and phenols 546-552 oxidation of 981, 988 photolysis of 873, 874, 988 radiolysis of 890-909, 1054, 1055 self-association of 544-546 Dimsyl anion... 

Organic hydroperoxides have also been used for the oxidation of sulphoxides to sulphones. The reaction in neutral solution occurs at a reasonable rate in the presence of transition metal ion catalysts such as vanadium, molybdenum and titanium - , but does not occur in aqueous media . The usual reaction conditions involve dissolution of the sulphoxide in alcohols, ethers or benzene followed by dropwise addition of the hydroperoxide at temperatures of 50-80 °C. By this method dimethyl sulphoxide and methyl phenyl sulphoxide have been oxidized to the corresponding sulphone in greater than 90% yields . A similar method for the oxidation of sulphoxides has been patented . Unsaturated sulphoxides are oxidized to the sulphone without affecting the carbon-carbon double bonds. A further patent has also been obtained for the reaction of dimethyl sulphoxide with an organic hydroperoxide as shown in equation (19). 

Petroleum ether with aniline, benzyl alcohol, dimethyl formamide, dimethyl sulphoxide, formamide, furfuryl alcohol, phenol or water. 

Fig. 31. Horse liver alcohol dehydrogenase ternary complex with NADH and the inhibitory substrate analogue dimethyl sulphoxide. Stereo drawing from the work of Branden and colleagues.

Fig. 32. Horse liver alcohol dehydrogenase. The full line shows positions in the apo-enzyme (Fig. 30) and the broken line shows positions in the ternary complex with NADH and dimethyl sulphoxide (Fig. 31). This figure therefore illustrates the movement of active site residues that occurs when the coenzyme and substrate analogue bind. Stereo drawing from the work of Branden and colleagues. 

The upper temperature at which polyelectrolytes can be utilised can be extended by substitution of a polar organic solvent for water in the electrolyte. Conductivities of up to 1 Q 1m 1 have been obtained for sulphonated PEEK using anhydrous pyrazole and imidazole at 200 C (Kreuer et al., 1998). Solvents used to form electrolytes in Nafion membranes have included alcohols, amines, propylene carbonate, dimethoxyethane, dimethyl form-amide, dimethyl sulphoxide and TV-methyl pyrrolidone. Typical conductivities for the latter three solvents are 10 to 1 O-lm 1 at room temperature, and the conductivity is thermally activated with activation energies in the range 9 to 24 kJ/mol (Doyle et al., 2001). 

Most research work on the use of supercritical water has been conducted batchwise and involved non-analytical determinative applications. Thus, supercritical water oxidation (SCWO) was proposed as an alternative treatment for hazardous waste disposal [191] and also as a commercial tool for decomposing trichloroethylene, dimethyl sulphoxide and isopropyl alcohol on a pilot plant scale [192]. Current commercially available equipment (the aqua Critox" system) is usable with industrial and municipal sludge, mixed (radioactive and organic, liquid and solid) waste and military waste. This commercially available treatment has a number of advantages, namely (a) because it uses an on-site treatment method, it avoids the need to transport hazardous materials (b) it ensures complete destruction of organic wastes and allows reuse of the effluent as process water with results that meet the regulations for drinking water and (c) no licence for effluent or air emissions is needed. 

In another sulphation study the kinetics of the reaction of sulphamic acid with 2-octanol to give sec-octylsulphate were found to be first order in sulphamic acid with energies and entropies of activation of 3.1 + 0.6 kcal mol-1 and 15 2 e.u. (in DMF) and 33.7 + 1.0 kcal mol -1 and 17 + 3 e.u. (in dimethyl sulphoxide)64. In dimethylformamide the mechanism involves the slow formation of DMF SO 3 followed by its rapid reaction with the alcohol to give R0S020NH4. 

Tervalent phosphorus acid derivatives are normally liquids or low-melting solids which can be purified by distillation, or sometimes by recrystallization from a non-polar solvent. Most are oxidized in contact with the atmosphere, and many are easily hydrolyzed, so they must be kept under an inert atmosphere (N2 or Ar) during all manipulations. Flasks should be predried and solvents dried and deoxygenated before use. Tervalent phosphorus acid derivatives are, with few exceptions, thermally stable and can be kept indefinitely in ampoules under an inert gas (many halophosphines dissolve stopcock grease and should not be kept in stoppered flasks for prolonged periods). Inert solvents are hydrocarbons, ethers and, for most compounds, dichloromethane, ethyl acetate and tertiary amines. Aminophosphines react vigorously with tetrachloromethane and slowly with trichloromethane, and most tervalent phosphorus acid derivatives are oxidized by dimethyl sulphoxide and react with alcohols. 

In cases where the more established kinetic approaches become insensitive, mixed solvent studies on rate of elimination may prove enlightening. Although p and knlko remain unchanged in the elimination of 2-arylethyl bromides with t-butoxide in t-butyl alcohol on the addition of dimethyl sulphoxide (0-2.23 M), a rate increase of 120 times is noted" . Smaller increases in rate are observed for similar variations in the concentration of added dipolar aprotic solvent in elimination from 1-phenylethyl bromide and 9-bromo-9,9 -bifluorenyP , but a steeper rise in rate is observed for 2,2-diphenylethyl tosylate. A cor-... 

The 5,6-dihydroxyindoles, including the parent system 1, are usually white-to-grey crystalline solids that melt with extensive decomposition and darkening. They are soluble in alcoholic solvents and acetone, less in acetonitrile, ethyl acetate, dimethyl sulphoxide (DMSO), tetrahydrofuran (THF), and water, and only sparingly soluble in hydrocarbons, e.g. benzene and light petroleum. A detailed physicochemical characterization of compound 1 was described by Murphy and Schultz (85JOC5873) (85JOC2790). The values for the first and second ionizations of indole 1 were determined as 8.9 and > 10.2, respectively. 5,6-Dihydroxy-1-methylindole 3 has values of 8.4 and 10.7 in water. 

---