Dimethylsulfoxide based oxidations

A variety of methods have been described to solve the task in solution.16 Common oxidative agents for this transformation include various heavy-metal reagents such as chromium-or ruthenium-based oxides, pyri-dine-S03, and dimethylsulfoxide (DMSO) in combination with acetic anhydride, carbodiimide, or oxalyl chloride for activation. One of the most prominent methods for the reliable conversion of sensitive compounds is the Dess-Martin reagent or its nonacetylated equivalent, 1-hydroxy-(17/)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX). 

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... 

Phosphorus pentafluoride Phosphorus pentasulfide Phosphorus pentoxide Phosphorus, red Phosphorus tribromide Phosphorus bichloride Water or steam Air, alcohols, water Formic acid, HF, inorganic bases, metals, oxidants, water Organic materials Potassium, ruthenium tetroxide, sodium, water Acetic acid, aluminum, chromyl dichloride, dimethylsulfoxide, hydroxylamine, lead dioxide, nitric acid, nitrous acid, organic matter, potassium, sodium water... 

The NMR spectrum shown in Figure 5 was obtained by dissolving hydralazine hydrochloride in deuterium oxide containing 3-(trimethylsilyl)-1-propane-sulfonic acid sodium salt (DSS). The series of peaks at 0, 0.6, 1.8, and 3 ppm are all due to the DSS. The peak at 4.8 ppm is due to HDO which forms on exchange with the solvent and the peaks at 8.01 and 8.61 ppm are due to the aromatic protons. The NMR spectrum of the base (Figure 6) was obtained in a 1 1 mixture of dimethylsulfoxide-d,- deuterochloroform. 

The amine 196 upon reaction with hydrogen sulfide in dimethylsulfoxide (DMSO) in the presence of base at 25-50 °C afforded the thiazine 197, allyl(2-mercaptopropyl)amine 198, and 3,7-dimethylperhydro[l,2,5]dithiazepine 199 in 10-17%, 2-31%, and 1-50% yields, respectively (Scheme 43) <2000RJC1243>. The formation of 199 is assumed via thiol 198, which reacted with a second hydrogen sulfide molecule to give dithiol 200. Subsequent oxidation of200 resulted in 199. In an alternative mechanistic pathway, the amine 196 can form the intermediate 201, which could cyclize to give 199. 

The Swern oxidation is the oxidation of alcohols to the corresponding carbonyl compounds using oxalyl chloride and dimethylsulfoxide and a base, usually triethylamine, at low temperatures. 

The high dielectric constant of dimethylsulfoxide (DMSO) at 46.6 makes it an excellent solvent for acid/base reactions of organic acids and pK oMso measurements have been made for over 1000 organic acids over a wide range 0< pK 35 [48]. However DMSO is oxidizing and it is a medium strength ligand and can substitute H2. This may explain why few pK Mso jiave been determined for hydrides. 

The reaction can also be catalyzed by Cu(I) ions supplied by elemental copper, thus further simplifying the experimental procedure-a small piece of copper metal (wire or turning) is all that is added to the reachon mixture, followed by shaking or stirring for 12-48 h [6, 23, 50]. Aqueous alcohols (methanol, ethanol, tert-butanol), tetrahydrofuran, and dimethylsulfoxide can be used as solvents in this procedure. Cu(ll) sulfate may be added to accelerate the reaction however, this is not necessary in most cases, as copper oxides and carbonates, the patina on the metal surface, are sufficient to initiate the catalytic cycle. Although the procedure based on copper metal requires longer reaction times when performed at ambient temperature, it usually provides access to very pure triazole products... 

Scheme 20.2S describes the work published by Kawasaki s group where they used a combination of dimethylsulfoxide and trifluoroacetic anhydride as source of trifluoroacetylated sulfonium ion 109 which reacted with 108 generating the new sulfonium salt 110 that underwent the loss of the sulfur-containing moiety promoted by nucleophilic attack. The nucleophile could be an alcohol, thiol, amine or organometallic species, or even another heterocyclic substrate. In cases where the nucleophile was a sulfoxide, the reaction led to an overall CH2 oxidation (Scheme 20.2S). Kawasaki s results suggest that this transformation, based on an interrupted Pummerer rearrangement, could be applied in the synthesis of biologically active tetrahydrocarbazoles and analogues fFigure 20.2T...

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