Dimethyl sulfoxide, acid-base equilibria

Sections 3.3.1 and 4.2.1 dealt with Bronsted acid/base equilibria in which the solvent itself is involved in the chemical reaction as either an acid or a base. This Section describes some examples of solvent effects on proton-transfer (PT) reactions in which the solvent does not intervene directly as a reaction partner. New interest in the investigation of such acid/base equilibria in non-aqueous solvents has been generated by the pioneering work of Barrow et al. [164]. He studied the acid/base reactions between carboxylic acids and amines in tetra- and trichloromethane. A more recent compilation of Bronsted acid/base equilibrium constants, determined in up to twelve dipolar aprotic solvents, demonstrates the appreciable solvent influence on acid ionization constants [264]. For example, the p.Ka value of benzoic acid varies from 4.2 in water, 11.0 in dimethyl sulfoxide, 12.3 in A,A-dimethylformamide, up to 20.7 in acetonitrile, that is by about 16 powers of ten [264]. 

The tautomerism of 4-aminopyrido[2,3- ]-l>2,6-thiadiazine-2,2-dioxide, an acid with a of 5.85, has been investigated by PSez et al. (Scheme 1). The 8/f-tautomer 10a is characterized by an ultraviolet (UV) maximum at 365 nm and the 1/f-tautomer 10b by a band at 320 nm, thus allowing the determination of the tautomeric equilibrium by UV spectroscopy. This conclusion that the aminopyridothiadiazinedioxide 10 exists as the 8f/-tautomer in aqueous and dimethyl sulfoxide (DMSO) solutions was based upon a comparison with the UV spectra of the 8-methyl derivative 11 (- max 365 nm) and the 1-methyl derivative 12 322 nm) <2004JST83>. 

The final proportions of the four possible ring isomers vary considerably among different sugars, depending on their thermodynamic stabilities. The equilibrium is also affected by the solvent for instance, the proportion of the furanose form is increased in dimethyl sulfoxide since the solvation of hydroxyl groups is decreased. Traces of acids or bases accelerate this interconversion. 

An interesting example of a Lewis acid/base reaction between neutral reactants is the formation of tris(n-butyl)phosphonium-dithiocarboxylate, ( -Bu)3P" — 82 , from tris(n-butyl)phosphane and carbon disulfide in solution. As expected, this equilibrium is strongly shifted in favour of the dipolar zwitterion with increasing solvent polarity (diethyl ether dimethyl sulfoxide) [272, 273]. 

Organic solvents influence the ionization constants of weak acids or bases in several ways (note that they influence the analytes and the buffer as well). Concerning ionization equilibria, an important solvent property is the basicity (in comparison to water), which reflects the interaction with the proton. From the most common solvents, the lower alcohols and acetonitrile are less basic than water. Dimethyl sulfoxide is clearly more basic. However, stabilization of all particles involved in the acido-basic equilibrium is decisive for the pKa shift as well. For neutral acids of type HA, the particles are the free, molecular acid, and the anion, A . In the equilibrium of bases, B, stabilization of B and its conjugated acid, HB, takes place. As most solvents have a lower stabilization ability toward anions (compared to water), they shift the pK values of adds of type HA to higher values in general. No such clear direction of the change is found for the pK values of bases however, they undergo less pronounced shifts. 

Acidity constants for ionization of weak carbon acids in water caimot be determined by direct measurement when the strongly basic carbanion is too unstable to exist in detectable concentrations in this acidic solvent. Substituting dimethyl-sulfoxide (DMSO) for water causes a large decrease in the solvent acidity because, in contrast with water, the aprotic cosolvent DMSO does not provide hydrogenbonding stabilization of hydroxide ion, the conjugate base of water. This allows the determination of the pfC s of a wide range of weak carbon acids in mixed DMSO/water solvents by direct measurement of the relative concentrations of the carbon acid and the carbanion at chemical equilibrium [3, 4]. The pfC s determined for weak carbon acids in this mixed solvent can be used to estimate pfC s in water. 

Determination of the acidity of hydrocarbons is more difficult. As most are very weak acids, very strong bases are required to cause deprotonation. Water and alcohols are far more acidic than most hydrocarbons and are unsuitable solvents for generation of hydrocarbon anions. A strong base deprotonates the solvent rather than the hydrocarbon. For synthetic purposes, aprotic solvents such as ether, THF, and dimethoxyethane are used, but for equilibrium measurements solvents that promote dissociation of ion pairs and ion clusters are preferred. Weakly acidic solvents such as dimethyl sulfoxide (DMSO), dimethylformamide (DMF), and cyclohexylamine are used in the preparation of moderately basic carbanions. The high polarity and cation-solvating ability of DMSO and DMF facilitate dissociation of ion pairs so that the equilibrium data obtained refer to the free ions, rather than to ion aggregates. 

Later, the same group reported the synthesis of a more acidic 4,6-dinitrodibenzocyclo-butane-1,8-diol [8] and examined equilibrium constants for hydrogen bonding with various bases [9] (Table 9.1). Binding affinity of dinitro substituted bisphenol to TMP was 40-fold higher compared to that of unsubstituted one (run 1). Similar but moderate effects were observed with respect to other hydrogen acceptors, HMPA, 2,6-dimethyl-y-pyrone (DMP), tetramethylenesulfoxide (TMSO), and dimethyl sulfoxide (DMSO) (runs 2-5). Thus, the... 

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