Substituent Effects in the Gas Phase

Having considered how solvents can affect the reactivities of molecules in solution, let us consider some of the special features that arise in the gas phase, where solvation effects are totally eliminated. Although the majority of organic preparative reactions and mechanistic studies have been conducted in solution, some important reactions are carried out in the gas phase. Also, because most theoretical calculations do not treat solvent effects, experimental data from the gas phase are the most appropriate basis for comparison with theoretical results. Frequently, quite different trends in substituent effects are seen when systems in the gas phase are compared to similar systems in solution. 

CHAPTER 4 STUDY AND DESCRIPTION OF ORGANIC REACTION MECHANISMS 

It is possible to measure equilibrium constants and heats of reaction in the gas phase by using mass spectrometers of special configuration. With proton-transfer reactions, for example, the equilibrium constant can be determined by measuring the ratio of two reactant species competing for protons. Table 4.13 compares of phenol ionizations. 

A comparison of phenol acidity in DMSO versus the gas phase also shows an attenuation of substituent effects, but not nearly as much as in water. Whereas the effect of ubstituents on AG for deprotonation in aqueous solution is about one-sixth that in the gas phase, the ratio for DMSO is about one-third. This result points to hydrogen bonding of the phenolate anion by water as the major difference in the solvating properties of water and DMSO.  

ITiscusaioa of (be techniques for gas-( haau equilibrium meaauiuncaita can be found in T. A. Lehman and M. M. Buisey, Ion Cyclotron Resonance ectrometry, Wiky-Interscience, New yfaik, 1976 M. T. Bowers, ed., Gas Phase Ion Chemistry, Vols. I and 2, Aeadetnic Press, New Ypik, 1979. 

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Another example of enhanced sensitivity to substituent effects in the gas phase can be seen in a comparison of the gas-phase basicity for a series of substituted acetophenones and methyl benzoates. It was foimd that scnsitivtiy of the free energy to substituent changes was about four times that in solution, as measured by the comparison of A( for each substituent. The gas-phase data for both series were correlated by the Yukawa-Tsuno equation. For both series, the p value was about 12. However, the parameter r" ", which reflects the contribution of extra resonance effects, was greater in the acetophenone series than in the methyl benzoate series. This can be attributed to the substantial resonance stabilization provided by the methoxy group in the esters, which diminishes the extent of conjugation with the substituents. 

While the substituent effect in the gas phase is assumed to be nearly entirely an enthalpy effect, it can be shown that in solution the substituent effect is largely the result of changes in AS. 

Another example of enhanced sensitivity to substituent effects in the gas phase can be seen in a comparison of the gas phase basicity for a series of substituted acetophenones and methyl benzoates. It was found that sensitivity of the free energy... 

This is opposite from the order in solution as revealed by the pK data in water and DMSO shown in Table 4.14. These changes in relative acidity can again be traced to solvation effects. In the gas phase, any substituent effect can be analyzed directly in terms of its stabilizing or destabilizing effect on the anion. Replacement of hydrogen by alkyl substituents normally increases electron density at the site of substitution, but this effect cannot be the dominant one, because it would lead to an ordering of gas-phase acidity opposite to that observed. The dominant effect is believed to be polarizability. The methyl... 

The application of (27) to these substituent effects using the gas-phase substituent constants listed in Table 15 provides excellent correlations. Figure 29 demonstrates the linear Y-T correlation for a-hydroxy-a-phenylethyl... 

Significantly low r values have been observed in the protonation equilibria (p7 BH+ values) of benzoyl compounds (Mishima et al, 1988, 1990c, 1996c). The trend in the r values mentioned above predicts that a stabilized carbocation will not require a large 7r-delocalization of the positive charge. Substituent effects on the gas-phase basicities (AG(co)h+) of the aromatic carbonyl compounds [30(R)], ArCOR (30) have been studied. 

Substituent effects for acidities of a series of aryl(trifluoromethylsulfonyl)methanes and arylbis(trifluoromethylsulfonyl)-methanes have been analysed successfully in terms of the Yukawa-Tsuno equation using substituent parameters in the gas phase. The resultant resonance demand parameter r value decreased linearly with increasing acidity of the gas-phase acidity values of the unsubstituted parent carbon acids, and the change of the r value was found to be related to the geometric parameters and natural charges of the conjugate carbanions calculated at B3LYP/6-31 lq-G(d,p). 

The observed acidities in the gas phase are interpreted in terms of the negative induction effect of the halo substituents however, the microscopic picture of the solvent effects in addition to such induction effects of the solute have not been clarified. 

Another area of gas-phase substituent effects that has attracted interest is the acidity of simple alcohols. In the gas phase, the order is r-BuOH > EtOH > MeOH 3>... 

The trend in acidity as a function of substituent is the same but the magnitude of the substituent effects is much larger in the gas phase. (The AAG° for any given substituent is about 10 times larger in the gas phase.)... 

Because carbocations are key intermediates in many nucleophilic substitution reactions, it is important to develop a grasp of their structural properties and the effect substituents have on stability. The critical step in the ionization mechanism of nucleophilic substitution is the generation of the tricoordinate carbocation intermediate. For this mechanism to operate, it is essential that this species not be prohibitively high in energy. Carbocations are inherently high-energy species. The ionization of r-butyl chloride is endothermic by 153kcal/mol in the gas phase. ... 

Compute the frequency associated with carbonyl stretch in solution with acetonitrUe for the carbonyl systems we looked at in the gas phase in Chapter 4. Run your calculations using RHF/6-31+G(d) with the Onsager SCRF model. Discuss the substituent effect on the predicted solvent effects. 

Computations can be carried out on systems in the gas phase or in solution, and in their ground state or in an excited state. Gaussian can serve as a powerful tool for exploring areas of chemical interest like substituent effects, reaction mechanisms, potential energy surfaces, and excitation energies. 

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