Isopolar transition-state reactions

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

Ground and transition states have a priori identical polarity, because no charges are developed during the reaction path. Following this rule, specific microwave effects would not be expected in these reactions (Fig. 4.8), as has been verified when the reactions were performed in a nonpolar solvent [13, 14). Solvent effects in these reactions are also small, or negligible, for the same reasons [67]. 

Such a conclusion is, nevertheless, connected with the synchronous character of the mechanism. If a stepwise process is involved (non-simultaneous formation of the two new bonds), as is the situation when dienes and (or) dienophiles are un-symmetrical or in hetero Diels-Alder reactions, a specific microwave effect could intervene as charges are developed in the transition state. This could certainly be true of several cycloadditions [68, 69] and, particularly, for 1,3-dipolar cycloaddi- 

During the course of a study of the [3+2]cycloaddition of azidomethyldiethyl-phosphonate to acetylenes and enamines leading to alkyltriazoles under solvent-free conditions, we observed that specific effects can be involved, depending on the nature of the substituents on the dipolarophiles [71] (Eq. 10, Table 4.6). They were explained by considering the nonsynchronous character of the mechanism. 

The synthesis of biologically significant fiuorinated heterocyclic compounds was accomplished by 1,3-dipolar cycloaddition of nitrones to fiuorinated dipolarophiles 

---

Solvent Effects on Isopolar Transition State Reactions... 

For example, the rate of the Diels-Alder cycloaddition reaction between 9-(hydroxymethyl)anthracene and A-ethylmaleimide, as shown in Eq. (5-159), is only slightly altered on changing the solvent from dipolar acetonitrile to nonpolar isooctane, as expected for an isopolar transition state reaction cf. Section 5.3.3. In water, however. 

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]. 

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],... 

The mechanisms of these unusual reactions are not known with certainty the temperature and solvent dependence of the product distribution and the rate constants suggest that isopolar transition states rather than zwitterionic intermediates are involved. ... 

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]. 

The dissociation rate of the dimer of the triphenylmethyl radical in 28 solvents was studied by Ziegler el al. [167]. The decomposition rate of azobisisobutyronitrile in 36 solvents was measured by different authors [183-185, 562], Despite the great variety of solvents, the rate constants vary only by a factor of 2... 4. This behaviour is typical for reactions involving isopolar transition states and often indicates, but does not prove, a radical-forming reaction. The lack of any marked solvent effects in most free-radical forming reactions will become more apparent after an examination of some further reactions presented in Table 5-8. 

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). 

Back to the starting point there is e qierimental data that has not yet been commented. Until now we have been dealing with a mechanism involving polar transition states that should have been affected to some extent by a change in the polarity of the medium. However, the fact is that the reactions of cinnamate 1 and hydroxylamine derivatives show no difference (either in stereochemistry or yields) when the solvent was changed from THF ( t 0.207) to EtOH 0.654). The laek of sensitivity to a change in the solvent polarity is a characteristic of the reactions involving concerted (isopolar) transition states. 

A number of important concerted organic reactions proceed through isopolar transition states examples are the Diels-Alder reaction, and the Cope and Claisen rearrangements. These processes are in fact specific cases of a whole family of reactions which have been termed pericyclic processes (Woodard and Hoffmann, 1969). Concerted pericyclic reactions proceeding via polar transition states are also well-known. 

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),... 

The observed range of solvent effects (less than a factor of four) for the ene reaction between 3-phenyl-l-7 -tolylpropene-(l) and diethyl azodicarboxylate, given in Eq. (5-45), is best explained by a concerted mechanism involving an isopolar six-centre transition state [136]. 

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. 

Ionic Liquid Effects on Reactions Proceeding through Isopolar and Radical Transition States... 

---