Dimethylsulfoxide acid-base reactions

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. 

One method used for the preparation of [Pt(en)2]Cl2 or [Pt(en)3]Cl4 is the direct reaction between ethylenediamine and PtCU or PtCLt, respectively. The technique is to add slowly the solid platinum salts to the liquid ethylenediamine. This addition is accompanied by a vigorous evolution of heat, which is to be expected whenever a strong acid is added to a strong base. Recall (Section 2.1) that in terms of the Lewis definition of acids and bases, the formation of coordination compounds involves an acid-base reaction. In this particular case, the platinum ions are the acids and ethylenediamine is the base. Metal dimethylsulfoxide complexes have been prepared and characterized. One method used to prepare some of these complexes is a direct reaction (12) in the absence of any added solvent. 

Figure 13.9 illustrates the reversible abstraction of a proton of 2,2, 4,4 -tetranitro-phenylmethane by a series of bases in 50% water-50% dimethylsulfoxide, where this acid has a dissociation constant of = 0.90, and that may proceed by general acid-base catalysis [6]. The general expression for the rate constant of this reaction is, according to eq. (13.25),... 

HMF is an important versatile sugar derivative and is a key intermediate between bio-based carbohydrate chemistry and petroleum based industrial organic chemistry (1, 2). The most coimnon feedstock for HMF is fructose and reactions are carried out in water-based solvent systems using acid catalysis (3,4). HMF is unstable in water at low pH and breaks down to form levulinic acid and formic acid, resulting in an expensive HMF recovery process. In strongly polar organic co-solvents, such as dimethylsulfoxide (DMSO), levuhnic acid formation is reduced and HMF yields are improved (5). 

In organic solvents the acidity functions H corresponding to hydrogen dissociation from neutral indicator acids were reported for solutions of alkali metal alkoxides in various alcohols (2), using nitroanilines (21), aminobenzenecarboxylic acids (22), or indols (23) as indicators. For addition reactions of methoxide and ethoxide ions to neutral indicator acids, acidity functions J (also denoted as Hr) based on use of nitrobenzenes (21) and a-cyanostilbenes (18) as indicators in methanol and dimethylsulfoxide-methanol and -ethanol mixtures were reported. Recently (24) the acidity function J- (denoted as Jm) was derived for methoxide ion solutions in methanol using substituted benzaldehydes as indicators. These scales involve arbitrary choice of water as the solvent for determination of the dissociation constant of the anchoring acid. 

Fischer and Zollinger have studied the reaction of p-chlorobenzenediazonium chloride with 2-naphthol-l-sulfonate. A very interesting dependence of the reaction products and reaction rate on the solvent was observed The initiaUy formed complex 102 decomposes under ring fragmentation in aqueous base (see (44) in Sect. 2.2.3) it does not react in water, ethanol or dimethylsulfoxide, reacts very slowly in acetone or glacial acetic acid to give a small amount of azo compound 7dJ, while in dichloromethane, chloroform, benzene or pyridine quantitative, though slow, formation of the azo compoimd is observed. Ba on kinetic measurements an Sisil-type mechanism was postulated for the formation of the azo dye 103 from the CT-complex 102... 

The efficiency depends upon the difference in the pK,s of the acids which also can be a function of the solvent. The rate is a function of the base and the solvent. Such bases as MH and MNH2 are insoluble in and react slowly in hydrocarbons or ethers, but solubilization of these bases by an additive leads to rapid metallations . In the polar aprotic solvents dimethylsulfoxide (DMSO), hexamethylphosphoramide (HMPA) and N,N-dimethylformamide (DMF) reaction (a) is rapid. Hexamethylphosphoramide causes tumors and should be handled in a hood with appropriate protective measures. Reaction... 

Appropriate alkyl iodides or bromides were reacted with 57 and 2-epi-Sl in the presence of Ag20 in CH3CN with yields ranging from 36 to 77% (74, Scheme 10) [34, 51]. However, with these conditions preparation of branched alkyl ethers was unsuccessful [51]. Reacting 57 with chloromethyl methyl ether, diisopropylethy-lamine, and catalytic DMAP in CH2CI2 afforded 75 in a 72% yield and was the first 1 derivative reported to have increased affinity at the KOP receptor relative to 1. [41, 52]. Based on the successful increase in affinity of derivative 75, additional simple alkoxymethyl ethers were obtained using appropriate alkyoxymethyl chloride with diisopropylethylamine in DMF (76-78). However, more complex alkoxymethyl derivatives were synthesized from the common methylthiomethyl ether intermediate (79), which was obtained from reaction of 57 with acetic acid, acetic anhydride, and dimethylsulfoxide (DMSO) [52]. Compound 79 was then... 

Another way to enhance ( )-enoate selectivity of a-alkoxy aldehyde reactions is available, based on the catalytic effect of benzoic acid in ether solvents (99a, 101b, 128, 131). Detailed stereochemical comparisons of catalyzed and uncatalyzed reactions are not available in the examples in Table 19, but entry 98 is reported to benefit significantly by comparison to the uncatalyed process (131). It has not been shown whether benzoic acid catalysis affects the mechanism of C—C bond formation or whether it equilibrates product stereochemistry in this case. The combination of the acid catalyst and the elevated reaction temperature in dimethoxyethane increases the risk of Z E equilibration. However, in an earlier example discussed in connection with Table 16, the ( )-enoate-enhancing effect of benzoic acid is due to kinetic control. It has also been shown that benzoic acid catalysis is more effective in CH2CI2 than in dimethylsulfoxide (99a). 

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... 

Recent work has indicated that solvents may even behave as phase transfer catalysts under certain conditions [50]. Generation of sulfur ylides by reaction of a sulfonium salt with a solid base was found to proceed via deprotonation of the solvent (Figure 5.21). It is believed that other weakly acidic solvents, such as rer -butanol and dimethylsulfoxide, behave in a similar manner, although it is not known whether these will function if they are present in just catalytic amounts. 

Abstract. Nucleophilic addition of amines to olefins which are activated by electron withdrawing substituents occurs readily in aqueous dimethylsulfoxide. The reaction comprises two steps (1) nucleophilic addition to form a zwitterionic complex (2) removal of the ammonio proton of the zwitterion by a base. In most cases the first step is rate limiting but in some cases proton transfer is rate limiting. The latter situation prevails either when the reverse of the nucleophilic attack step is very rapid, as in the reaction of morpholine with benzylidenemalononitrile, or when the rate of proton transfer is depressed by a steric effect, as in the reaction of morpho-line with 1,l-dinitro-2,2-diphenylethylene. The steric effects in this latter system are among the most dramatic ones reported to date. Our data also show that the kinetic barrier to nucleophilic attack is substantially higher for nitro than for cyano activated olefins. This effect seems to be related to the well known fact that proton transfers involving nitro activated carbon acids are much slower than those of cyano activated carbon acids. 

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