Solvents non-HBD

We have already encountered the ir, a, and p quantities. The 8h term is inserted to account for the cavity effect. Equation (8-80) is a 12-parameter equation for which considerable generality is claimed, in that it is said to be applicable to chemical rates and equilibria, spectra, solubilities, partition coefficients, and even biological responses. Usually, of course, by judicious selection of solvents, it is possible to reduce the number of parameters by ensuring that some terms are negligible.An example requiring most of the parameters in Eq. (8-80) is the solvolysis/dehydrohalogenation of r-butyl chloride in 21 HBD and non-HBD solvents, for which this correlation was found ... 

In the case of non-HBD solvents, such as DMSO, the measured pK values are absolute (that is, free from ion pairing) and can be directly compared with gas-phase acidities6 in addition, knowledge of the heats of ionization in DMSO7 allows the evaluation of a possible entropy effect when the two phases are compared. The mechanism of proton transfer between oxygen and nitrogen acids and bases in aqueous solution has been reviewed8. 

Another remarkable Lewis basicity scale for 75 non-HBD solvents has been established by Gal and Maria [211, 212]. This involved very precise calorimetric measurements of the standard molar enthalpies of 1 1 adduct formation of EPD solvents with gaseous boron trifluoride, A//p gp, in dilute dichloromethane solution at 25 °C, according to Eq. (2-10a). 

Acceptor numbers are less than 10 for nonpolar non-HBD solvents, they vary between about 10... 20 for dipolar non-HBD solvents, and they cover a wide range of about 25... 105 for protic solvents cf. Table 2-5). Surprisingly, benzene and tetra-chloromethane have stronger electrophilic properties than diethyl ether and tetrahy-drofuran. Acceptor numbers are also known for binary solvent mixtures [70, 213]. 

In principle, such interactions should also apply to other solvents resembling water, and therefore the more general term solvophobic interactions has been proposed [80, 343]. In fact, analogous water-like behaviour has been observed with self-associated solvents other than water, e.g. ethanol [81], glycerol [82], ethylammonium nitrate [227], and some dipolar non-HBD solvents [228]. 

Streitwieser et al. [160] and BordweU et al. [161] used the lyate ions of organic solvents such as cyclohexylamine and dimethyl sulfoxide in the determination of the C—H acidity of weak organic carbon acids. Using super base systems such as alkali metal salts of cyclohexylamine [i.e. lithium and cesium cyclohexylamides) [160] and dimethyl sulfoxide (sodium dimsyl) [161] in an excess of these non-HBD solvents, relative acidity scales for weak carbon acids have been established. In this way, values for the ionization of over a thousand Bronsted acids in dimethyl sulfoxide have... 

Since hydrogen-bonding is a hard acid-hard base interaction, small basic anions prefer specific solvation by protic solvents. Hence, the reactivity of F , HO , or CH3O is reduced most on going from a dipolar non-HBD solvent such as dimethyl sulfoxide to a protic solvent like methanol. Dipolar non-HBD solvents are considered as fairly soft compared to water and alcohols [66],... 

Bordwell et al [135] have pointed out that solvents referred to as dipolar aprotic are in fact not aprotic. In reactions employing strong bases their protic character can be recognized. Therefore, instead of dipolar aprotic the designation dipolar nonhydroxylic or better dipolar non-HBD solvents is strongly recommended. Cf. Section 2.2.5 and 3.4 (footnote). In order to avoid confusion, the nomenclature proposed by Chastrette et al [138] is retained in Fig. 3-6. 

The ionisation constants of many acidic organic compounds determined in water [110a] and in twelve of the most popular dipolar non-HBD solvents [110b] have been compiled, as have the methods of determination [111] and prediction [112] of p.Ka values. Particular attention has been paid to C—H acidic compounds [113]. Whereas the ionisation constants of Bronsted acids and bases for aqueous solutions are well known, the corresponding pAa values for nonaqueous solutions are comparatively scarce. 

In non-HBD solvents such as n-heptane, tetrachloromethane, diethyl ether, deuterio-tri-chloromethane, and dimethyl sulfoxide, tropolone transfers its proton to triethylamine to give an ion pair, which is in equilibrium with the non-associated reactants. There is no formation of a hydrogen-bonded complex between tropolone and triethylamine because of the fact that tropolone itself is intramolecularly hydrogen-bonded. The extent of the ion pair formation increases with solvent polarity. In polar HBD solvents such as ethanol, methanol, and water, this proton-transfer equilibrium is shifted completely towards the formation of triethylammonium tropolonate [171]. 

A simple example of an intramolecular Lewis acid/base reaction (thus avoiding the association step) is the xanthene dye rhodamine B, which exists in solution either in the red-coloured zwitterionic form (26a) or as the colourless lactonic form (26b) [175, 221, 222]. Solutions of rhodamine B in non-HBD solvents such as dimethyl sulfoxide,... 

A typical example of such reactions is the exothermic Sn2 nucleophilic displacement reaction Cl -I- CH3—Br Cl—CH3 - - Br . Table 5-2 provides a comparison of Arrhenius activation energies and specific rate constants for this Finkelstein reaction in both the gas phase and solution. The new techniques described above cf. Sections 4.2.2 and 5.1) have made it possible to determine the rate constant of this ion-molecule reaction in the absence of any solvent molecules in the gas phase. The result is surprising on going from a protic solvent to a non-HBD solvent and then further to the gas phase, the ratio of the rate constants is approximately 1 10 10 The activation energy of this Sn2 reaction in water is about ten times larger than in the gas phase. The suppression of the Sn2 rate constant in aqueous solution by up to 15 orders of magnitude demonstrates the vital role of the solvent. 

This differential solvation of reactants and activated complex is greater for protic solvents because protic, i.e. HBD solvents, are more sensitive to charge delocalization than aprotic, i.e. non-HBD solvents, due to reduced hydrogen-bonding with increasing charge delocalization. This is the main reason for the large rate enhancements in dipolar non-HBD solvents relative to protic solvents cf. Table 5-2) [6]. 

In the SnI solvolysis reaction of 2-chloro-2-methylpropane, leading mainly to t-butanol and t-butyl ethers together with some f-butene, the term solvolysis is normally restricted to the reaction in water and other HBD solvents. In non-HBD solvents, however, the only reaction product is f-butene. For convenience, the term solvolysis is often used in the literature to cover both types of reaction, solvolysis and dehydrohalogenation of 2-chloro-2-methylpropane, because the solvent-dependent rate-determining step of both reactions, S l and El, is the same. For a detailed review on the heterolysis of tertiary haloalkanes in the gas phase and in solution, see G. F. Dvorko, E. A. Ponomareva, and N. 1. Kulik, Usp. Khim. 53, 948 (1984) Russ. Chem. Rev. 53, 547 (1984). 

Other examples of this type of reaction are Sn2 reactions between azide ion and 1-bromobutane [67], bromide ion and methyl tosylate [68], and bromide ion and iodoethane [497]. In changing the medium from non-HBD solvents (HMPT, 1-methylpyrrolidin-2-one) to methanol, the second-order rate constants decrease by a factor of 2 10 [67], 9 10 [68], and 1 10 [497], respectively. The large decrease in these rate constants in going from the less to the more polar solvent is not only governed by the difference in solvent polarity, as measured by dipole moment or relative permittivity, but also by the fact that the less polar solvents are dipolar aprotic and the more polar solvents are protic cf. Section 5.5.2). 

In agreement with the separation of unlike charges during the activation process, an increase in rate by up to a factor of 50 with increasing solvent polarity has been found for reaction (5-26), carried out in thirteen non-HBD solvents [503], The absence of base-catalysis suggests that specific solvent effects are negligible in non-HBD solvents. In protic solvents, however, specific solvation of the piperidine nucleophile leads to a diminution in rate with increasing HBD ability of the hydroxylic solvents [503],... 

We shall conclude this Section with an example of a reaction that undergoes an extreme rate acceleration with an increase in solvent polarity. Thermolysis of a-chlorobenzyl methyl ether in a series of non-nucleophilic, non-HBD solvents shows rate variations up to 10, encompassing a range of 30 kJ/mol (7 kcal/mol) [112], This dramatic solvent effect is best explained by a mechanism involving ionization of the C—Cl bond to form an ion pair, followed by a nucleophilic attack by Cl on CH3 to give an aldehyde and chloromethane cf. Eq. (5-41). 

If one compares the rate constants for the same Menschutkin reaction with Kirkwood s parameter in thirty-two pure aprotic and dipolar non-HBD solvents [59, 64], one still finds a rough correlation, but the points are widely scattered as shown in Fig. 5-11. 

Extending the media used for the Menschutkin reaction to protic solvents such as alcohols leads to an even worse correlation, as shown in Fig. 5-12 for the quaternization of l,4-diazabicyclo[2.2.2]octane with (2-bromoethyl)benzene studied in a total of thirty-six solvents [65], The group of protic solvents is separated from the assembly of non-HBD solvents, each group showing a very rough but distinct correlation with the function of relative permittivity. Such behaviour has also been observed for several other Menschutkin reactions [60, 61],... 

A somewhat better correlation using values of Ig ki at 120 °C was obtained by Koppel and Pal m [250], but again protic and some non-HBD solvents do not conform to the expected linear pattern. From the slope of the estimated straight line, a value of = 10 Cm = 9.2 D for the activated complex was calculated, which although... 

Fig. 5-15. Correlation between g[k/krx,) and 1/sr for the alkaline hydrolysis of methyl propionate in eight acetone/water mixtures at 25 °C (o) [252], and for the Sn2 reaction between the azide anion and 1-bromobutane in six pure dipolar non-HBD solvents at 25 °C ( ) [67] (rate constants relative to the solvent with the largest dielectric constant).

Since the protic solvent is usually in large excess, its participation in the reaction cannot generally be established by means of kinetic measurements. However, if the reaction is carried out in a non-HBD solvent e.g. CeHe, CCI4), the effect of addition of small amounts of a protic solvent is easily observable. Thus, the Sn2 reaction between... 

These results are supported by the observation that dipolar non-HBD solvents such as A,A-dimethylformamide or dimethyl sulfoxide, in spite of their high relative permittivities (36.7 and 46.5) and their high dipole moments (12.3 10 and 13.0-10 Cm), favour neither the ionization of haloalkanes nor SnI reactions cf. Section 2.6). Dipolar non-HBD solvents cannot act as hydrogen-bond donors and are therefore poor at solvating the departing anions. Thus, the anchimerically assisted ionization of 4-methoxyneophyl tosylate, shown in Eq. (5-102), is nine times faster in acetic acid than in dimethyl sulfoxide. This is in spite of the fact that the relative permittivity of acetic acid is eight times smaller than that of dimethyl sulfoxide also the dipole moment of acetic acid is smaller than that of dimethyl sulfoxide [265],... 

It is furthermore remarkable that an approximately linear relationship between (fir — l)/(2er + 1) and Ig k values for reaction (5-102), measured in 19 solvents, is found only for non-HBD solvents [cf. Eq. (5-87) in Section 5.4.3), whereas protic solvents are much better ionizing media than their relative permittivity would suggest [265]. For example, acetic acid and tetrahydrofuran have very similar relative permittivities (6.2 and 7.6, respectively), and yet ionization in acetic acid exceeds that in tetrahydrofuran by a factor of 2 10 The reason for this extraordinary rate acceleration is again that the departing tosylate is better solvated due to hydrogen bonding in the protic solvent. The ability of the protic solvent to form hydrogen bonds is not reflected in its relative permittivity or in the dipole moment [265]. 

In this connection, it is noteworthy that the retarding effect of protic solvents on a given Sn2 reaction can also depend on the nature of the non-HBD solvent used [268, 269, 584]. Addition of a basic solvent may lead to a rate acceleration since the base can now compete with the nucleophile for hydrogen-bond formation with the protic solvent. Thus, the Sn2 reaction (5-105) is accelerated by addition of 1,4-dioxane to a protic solvent such as methanol as reaction medium [268]. 

Table 5-15. Relative nucleophilic reactivities of free anions for Sn2 reactions in various protic and dipolar non-HBD solvents (nos. 1... 5) as well as in molten salts (no. 6 and no. 7) and in the gas phase (no. 8).

It is apparent that the order of anion nucleophilicity is almost completely reversed on transfer from protic to dipolar non-HBD solvents. Especially for halide ions, the relative reactivity is completely reversed in the two classes of solvents whereas the order of reactivity is I > Br > Cl > F in the protic solvent methanol (reactions no. 1 and no. 2 in Table 5-15), in dipolar non-HBD solvents such as iV,iV-dimethylformamide (no. 2), acetone (no. 3), dimethyl sulfoxide (no. 4), and acetonitrile (no. 5) the sequence of nucleophilicity is reversed. The traditional order of halide nucleophilicities, I > Br > Cl [261], applies only when the nucleophile is deactivated through solvation by... 

Reaetions no. 6 and no. 7 in Table 5-15 demonstrate that with molten quaternary ammonium salts as solvents, where deaetivation by anion solvation is absent, the halide ions show the same nueleophilie order as in dipolar non-HBD solvents [283, 284], This is in aeeordanee with the theory of protie/dipolar non-HBD medium effeets on X nueleophilieity [6j. It has been suggested that fused-salt experiments should provide a good model for the determination of intrinsie relative nueleophilieities of anions towards saturated earbon atoms [284],... 

The results for reaetion no. 8 in Table 5-15 indieate that nueleophilie reaetivities of anions obtained in the gas phase are essentially in the same order as in molten salts and in dipolar non-HBD solvents [285, 290]. This again suggests that speeifie solvation of the anions is responsible for the reversed order obtained in protie solvents relative to dipolar non-HBD solvents. Whereas the relative nueleophilieities in aeetonitrile are similar to those found in the gas phase [282, 285, 290], the absolute gas-phase rates are some orders of magnitude greater than those in aeetonitrile. The speeifie rates of displacement reactions of anions with halomethanes exceed those in solution by factors of up to >10 [285, 290]. These large differences in absolute rates demonstrate the moderating influence of the solvent on all the reactivities [282]. See also Chapter 5.2. 

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