Activated isopolar

Isopolar activated complexes differ very little or not at all in charge separation or charge distribution from the corresponding initial reactants. These complexes are formed in pericyclic reactions such as Diels-Alder cydoadditions and the Cope rearrangement. 

When there is no change in the charge distribution in the reaction, as in free radical or isopolar reactions, the Hughes-Ingold rules are inoperative. The solvent polarity may play a minor role only, compared with other effects, such as differences in the volume requirements for cavity formation in highly structured solvents or of the hydrogen bonding abilities of the reactants and the activated... 

Solvent effect on rate constants. In this section, the rate constant will be predicted qualitatively in CO2 for the Diels-Alder cycloaddition of isoprene and maleic anhydride, a reaction which has been well-characterized in the liquid state (23,24). In a previous paper, we used E data for phenol blue in ethylene to predict the rate constant of the Menschutkin reaction of tripropylamine and methyliodide (19). The reaction mechanisms are quite different, yet the solvent effect on the rate constant of both reactions can be correlated with E of phenol blue in liquid solvents. The dipole moment increases in the Menschutkin reaction going from the reactant state to the transition state and in phenol blue during electronic excitation, so that the two phenomena are correlated. In the above Diels-Alder reaction, the reaction coordinate is isopolar with a negative activation volume (8,23),... 

Organic reactions can be loosely grouped into three classes depending on the character of the activated complex through which these reactions can proceed dipolar, isopolar, and free-radical transition-state reactions [15, 468]. 

From the first-order rate constants obtained in different solvents (in sealed ampoules), it is apparent that this isomerization is not very sensitive to the polarity of the medium, in accordance with an isopolar, six-membered activated complex [156]. A similar small solvent effect has been observed for the [3,3]sigmatropic rearrangement of allyl S-methyl xanthate to allyl methyl dithiol carbonate [559]. 

The conrotatory cyclization of fl//-cw-deca-2,4,6,8-tetraene to traw-7,8-dimethyl-cycloocta-l,3,5-triene has been studied in solvents of different polarity [157]. In agreement with a synchronous eonrotatory ring closure via an isopolar activated complex, the solvent effect is negligible as shown by the relative first-order rate constants in Eq. (5-52). 

The small inverse dependence of the first-order rate constant on solvent polarity is in agreement with a concerted electrocyclic ring cleavage through an isopolar activated complex to vinylketene, which is converted into the corresponding ester in alcoholic solvents [158]. 

From these results, it is clear that this reaction meets the requirements for a peri-cyclic reaction involving an isopolar activated complex. 

Another more recent example of a cheletropic reaction, studied in various solvents, is the addition of aryl-halocarbenes (generated photolytically from diazirines) to tetramethylethene to give the corresponding cyclopropane derivatives [820], The addition of chlorophenylcarbene is only about three times faster in ethyl acetate than in pentane, as befits an isopolar activated complex. 

Finally, it should be mentioned that no strict limit between reactions with dipolar and isopolar activated complexes exists. Some borderline cases with significant but relatively small charge separation in going from the initial to the transition state, with correspondingly small solvent rate effects, have been mentioned in this Section. 

Most criteria for mechanisms depend upon intramolecular and extramolecular perturbation of the reacting system. A change in the medium is an extramolecular perturbation of the original system. The solvent effects produced by this perturbation can be predicted, as shown in Table 5-10, by taking into account whether or not the activated complex is dipolar or isopolar with the respect to the initial reactants. Only a small... 

Apart from the selection of reactions involving dipolar, isopolar, or free-radical activated complexes used to demonstrate the qualitative theory of solvent effects by Hughes and Ingold [16, 44] in the preceding sections, further illustrative examples can be found in the literature e.g. [14, 15, 18, 21, 23, 26, 29, 460, 468]). 

The final limitation of the pure electrostatic theory is its inability to predict solvent effects for reactions involving isopolar transition states. Since no creation, destruction, or distribution of charge occurs on passing from the reactants to the activated complex of these reactions, their rates are expected to be solvent-independent. However, the observed rate constants usually vary with solvent, although the variations rarely exceed one order of magnitude [cf. Section 5.3.3). These solvent effects may be explained in terms of cohesive forces of a solvent acting on a solute, usually measured by the cohesive pressure of the solvent [cf. Section 5.4.2). 

Since [4 + 2]cycloaddition and ene reactions are generally assumed to proceed in a concerted manner via isopolar activated complexes, they should exhibit virtually the same small, often negligible, response to changes in solvent polarity. This is what, in fact, has been found cf. for example [138, 682, 683]. However, two-step [2 + 2]-cycloaddition reactions of singlet oxygen to suitably substituted electron-rich alkenes proceed via dipolar activated complexes to zwitterionic intermediates (1,4-dipoles or perepoxides). In this case, the relative amounts of 1,2-dioxetane and allylic hydroperoxides or e do-peroxides should vary markedly with solvent polarity if two or even all three of the reaction pathways shown in Eq. (5-145) are operative [681, 683, 684]. 

Not only Diels-Alder cycloadditions but also 1,3-dipolar cycloaddition reactions can be subject to hydrophobic rate enhancements. For example, the reaction of C,N-diphenylnitrone with di-n-butyl fumarate at 65 °C to yield an isoxazolidine is about 126 times faster in water than in ethanol, while in nonaqueous solvents there is a small 10-fold rate decrease on going from n-hexane to ethanol as solvent - in agreement with an isopolar transition-state reaction [cf. Eq. (5-44) in Section 5.3.3] [858]. Because water and ethanol have comparable polarities, the rate increase in water cannot be due to a change in solvent polarity. During the activation process, the unfavourable water contacts with the two apolar reactants are reduced, resulting in the observed rate enhancement in aqueous media. Upon addition of LiCl, NaCl, and KCl (5 m) to the aqueous reaction mixture the reaction rate increases further, whereas addition of urea (2 m) leads to a rate decrease, as expected for the structure-making and structure-breaking effects of these additives on water [858]. 

Similar pressure effects have been observed in the 1,3-dipolar cycloaddition of diazo-diphenylmethane to various alkenes. This is in agreement with a concerted mechanism involving an isopolar activated complex [752, 753] cf. Section 5.3.3. For the 1,3-dipolar cycloaddition of diazo-diphenylmethane to dimethyl acetylenedicarboxylate at 25 °C in n-hexane (AF = —24 cm mol ) and in acetonitrile (AF = —15 cm mol ), the solvent-induced difference AAF is only 9 cm mol this corresponds to a very small rate constant solvent effect, k2(CH3CN)/A 2(n-C6Hi4) = 3.4 [752]. 

Contrary to reactions going through isopolar transition states, reactions of types 3 to 8 in Table 5-25, which involve formation, dispersal or destruction of charge, should exhibit large solvent effects on their activation volumes. This is shown in Table 5-27 for the Sn2 substitution reaction between triethylamine and iodoethane [441], an example of the well-known Menschutkin reaction, the pressure dependence of which has been investigated thoroughly [439-445, 755],... 

Fluorinated derivatives play an important role in pharmaceutical and agrochemical compounds of interest. In fact, approximately 20% of the pharmaceuticals available in the market contain fluorine. The difluoromethylene group is isopolar and isosteric to the ethereal oxygen atom or the hydroxymethylene group, which are useful for the creation of biologically active compounds. 

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