Enthalpic control

Extreme cases were reactions of the least stabilized, most reactive carbene (Y = CF3, X = Br) with the more reactive alkene (CH3)2C=C(CH3)2, and the most stabilized, least reactive carbene (Y = CH3O, X = F) with the less reactive alkene (1-hexene). The rate constants, as measured by LFP, were 1.7 x 10 and 5.0 X lO M s, respectively, spanning an interval of 34,000. In agreement with Houk s ideas,the reactions were entropy dominated (A5 —22 to —29e.u.). The AG barriers were 5.0 kcal/mol for the faster reaction and 11 kcal/ mol for the slower reaction, mainly because of entropic contributions the AH components were only —1.6 and +2.5 kcal/mol, respectively. Despite the dominance of entropy in these reactive carbene addition reactions, a kind of de facto enthalpic control operates. The entropies of activation are all very similar, so that in any comparison of the reactivities of alkene pairs (i.e., ferei)> the rate constant ratios reflect differences in AA//t, which ultimately appear in AAG. Thus, car-benic philicity, which is the pattern created by carbenic reactivity, behaves in accord with our qualitative ideas about structure-reactivity relations, as modulated by substiment effects in both the carbene and alkene partners of the addition reactions. " Finally, volumes of activation were measured for the additions of CgHsCCl to (CH3)2C=C(CH3)2 and frani-pentene in both methylcyclohexane and acetonitrile. The measured absolute rate constants increased with increasing pressure Ayf ranged from —10 to —18 cm /mol and were independent of solvent. These results were consistent with an early, and not very polar transition state for the addition reaction. 

The electronic nature of silylsilver intermediate was interrogated through inter-molecular competition experiments between substituted styrenes and the silylsilver intermediate (77).83 The product ratios from these experiments correlated well with the Hammett equation to provide a p value of —0.62 using op constants (Scheme 7.19). Woerpel and coworkers interpreted this p value to suggest that this silylsilver species is electrophilic. Smaller p values were obtained when the temperature of the intermolecular competition reactions was reduced [p = — 0.71 (8°C) and —0.79 (—8°C)]. From these experiments, the isokinetic temperature was estimated to be 129°C, which meant that the product-determining step of silver-catalyzed silylene transfer was under enthalpic control. In contrast, related intermolecular competition reactions under metal-free thermal conditions indicated the product-determining step of free silylene transfer to be under entropic control. The combination of the observed catalytically active silylsilver intermediate and the Hammett correlation data led Woerpel and colleagues to conclude that the silver functions to both decompose the sacrificial cyclohexene silacyclopropane as well as transfer the di-terf-butylsilylene to the olefin substrate. 

Despite the dominance of entropy in these reactive carbene addition reactions a kind of defacto enthalpic control operates the entropies of activation are all very similar, so that in any comparison of the reactivities of alkene pairs (i.e., rgi), the rate constant ratios reflect differences in AAHi, which ultimately appear in AAGf Thus carbenic philicity, which is the pattern created by carbenic reactivity, behaves in accord with our qualitative ideas about structure/reactivity relations, as modulated by substituent effects in both the carbene and alkene partners of the addition reactions. [66,99]... 

The formation of enthalpically controlled 1 1 and 2 1 (host guest) complexes between a-cyclodextrin and Ph-Me sulfides has been observed in a kinetic and thermodynamic study of the a-cyclodextrin-mediated reaction of substituted Ph-Me sulfides with j-CPBA and peroxomonosulfate. The enthalpically controlled 1 1 cyclodextrin- j-CPBA complex is also formed. Peroxomonosulfate does not form any such complex. The reaction rates are analysed using the transition-state pseudoequilibrium approach. Enthalpy-entropy compensation plots for transition-state pseudoequilibrium constant Kjs give slopes close to unity." ... 

A good example for such a situation is a recent report on the synthesis of the macrotricyclic core 63 of roseophilin [40,41]- RCM was able to form the rather strained ansa chain of this target molecule only after the cyclization had been biased by a conformational control element X which helps to bring the unsaturated chains closer together and lowers the enthalpic barrier during ring formation (Scheme 18). 

The effective molarity (EM) is formally the concentration of the catalytic group (RCOO- in [5]) required to make the intermolecular reaction go at the observed rate of the intramolecular process. In practice many measured EM s represent physically unattainable concentrations, and the formal definition is probably relevant only in reactions (which will generally involve very large cyclic transition states) where the formation of the ring or cyclic transition state per se is enthalpically neutral, or in diffusion-controlled processes. For the formation of small and medium-sized rings and cyclic transition states the EM as defined above contains, and may indeed be dominated by, the enthalpy of formation of the cyclic form. This topic has been discussed briefly by Illuminati et al. (1977) and will be treated at greater length in a future volume in this series. 

If the backbone as well as the side chains consist of flexible units, the molecular conformation arises out of the competition of the entropic elasticity of the confined side chains and the backbone [ 153 -155]. In this case, coiling of the side chains can occur only at the expense of the stretching of the backbone. In addition to the excluded volume effects, short range enthalpic interactions may become important. This is particularly the case for densely substituted monoden-dron jacketed polymers, where the molecular conformation can be controlled by the optimum assembly of the dendrons [22-26,156]. If the brush contains io-nizable groups, the conformation and flexibility may be additionally affected by Coulomb forces depending on the ionic strength of the solvent [79,80]. 

The behavior of the nonpolar bonded phases, as well as the column packings based on crossbnked organic polymers of low polarity, however, differs from that of polar column packings and the classical solvent strength concept should be reevaluated. This is especially important for the alkyl bonded phases (Section 16.8.1). In this case, surface and interface adsorption of polymer species (Section 16.3.5) plays a less important role and macromolecules are mainly retained by the enthalpic partition (absorption) (Section 16.3.6). In order to ensure this kind of retention of polymer species, the mobile phase must push them into the solvated bonded phase. Therefore the interactions of mobile phase with both the bonded phase and (especially) with the sample macromolecules—that is, the solvent quality—extensively controls retention of latter species within the alkyl bonded phases. 

In conclusion, the enthalpic partition processes in the columns for polymer HPLC substantially differ from the adsorption processes. Enthalpic partition can be employed for the separation of polymers of the low-to-medium polarity in combination with the alkyl bonded phases on silica gels. The extent of the enthalpic partition and consequently also of the polymer retention is controlled primarily by the thermodynamic quality of eluent toward separated species and by the extent of the bonded phase solvation. 

The unconventional applications of SEC usually produce estimated values of various characteristics, which are valuable for further analyses. These embrace assessment of theta conditions for given polymer (mixed solvent-eluent composition and temperature Section 16.2.2), second virial coefficients A2 [109], coefficients of preferential solvation of macromolecules in mixed solvents (eluents) [40], as well as estimation of pore size distribution within porous bodies (inverse SEC) [136-140] and rates of diffusion of macromolecules within porous bodies. Some semiquantitative information on polymer samples can be obtained from the SEC results indirectly, for example, the assessment of the polymer stereoregularity from the stability of macromolecular aggregates (PVC [140]), of the segment lengths in polymer crystallites after their controlled partial degradation [141], and of the enthalpic interactions between unlike polymers in solution (in eluent) [142], as well as between polymer and column packing [123,143]. 

In this case, enthalpic interactions within the HPLC system exceed the exclusion effects (Eigure 16.3b). The retention volumes of polymer species as a rule exponentially increase with their molar masses. The limitations of the resulting procedures were elucidated in Section 16.3 the retention of (high)polymers is usually so large that these do not elute from the column (Section 16.6). Therefore, the majority of enthalpy controlled HPLC procedures is applicable only to oligomers—up to... 

The principle of the liquid chromatography under critical conditions (LC CC) was elucidated in Section 16.3.3. The mutual compensation of the exclusion—entropy and the interaction—enthalpy-based retention of macromolecules can be attained when applying in the controlled way the interactions that lead to either adsorption or enthalpic partition. The resulting methods are called LC at the critical adsorption point (LC CAP) or LC at the critical partition point (LC CPP), respectively. The term LC at the point of exclusion-adsorption transition (LC PEAT) was also proposed for the procedures employing compensation of exclusion and adsorption [161]. It is anticipated that also other kinds of enthalpic interactions, for example the ion interactions between column packing and macromolecules can be utilized for the exclusion-interaction compensation. 

Similar to other coupled methods of polymer HPLC, for example, LC CC (Section 16.5.2), the choice of the column packing and the mobile phase components for EG-LC depends on the retention mechanism to be used. Adsorption is preferred for polar polymers applying polar column packings, usually bare silica or silica bonded with the polar groups. The eluent strength controls polymer retention (Sections 16.3.2 and 16.3.5). The enthalpic partition is the retention mechanism of choice for the non polar polymers or polymers of low polarity. In this case, similar to the phase separation mechanism, mainly the solvent quality governs the extent of retention (Sections 16.2.2, 16.3.3, and 16.3.7). It is to be reminded that even the nonpolar polymers such as poly(butadiene) may adsorb on the surface of bare silica gel from the very weak mobile phases and vice versa, the polymers of medium polarity such as poly(methyl methacrylate) can be retained from their poor solvents (eluents) due to enthalpic partition within the nonpolar alkyl-bonded phases. 

The principle of enthalpy-assisted SEC (ENA SEC) is evident from Figure 16.3c and d (Section 16.3.3). The exclusion mechanism governs the order of elution that is the retention volumes decrease with the rising molar mass of sample. The presence of the controlled enthalpic interactions, however, raises the separation selectivity. 

The rates of hydrogen atom abstractions by radicals are subject to the same factors that control rates of alkene additions [130]. Both enthalpic and polar... 

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