PROTON TRANSFER AND THE PRINCIPLES OF STABILITY

Acid and Base Generic Groups and the Proton Transfer Path Conjugate Bases and Acids Proton Transfer Reactions Favor Neutralization Charge Types 

Stronger Acids Have Lower pKg Values Species vs. pH Graph Media pH Crosscheck Acidic Media Contain Powerful Electrophiles and Weak Nucleophiles Basic Media Contain Excellent Nucleophiles and Weak Electrophiles No Medium Can Be Both Strongly Acidic and Strongly Basic Common Acids and Their pKg Values Common Bases and Their pKapH Values 

3 STRUCTURAL FACTORS THAT INFLUENCE ACID STRENGTH 

Structural Basis of Acidity Electronegativity Strength of the Bond to H Charge Resonance Inductive/Field Hydrogen Bonding Aromaticity Extrinsic Factors 

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A new Chapter 3, Proton Transfer and the Principles of Stability, has been added to thoroughly develop how structure determines reactivity using a reaction from general chemistry. Proton transfer mechanisms and product predictions are introduced, setting up the discussion of organic reactions. 

This normal sequence of events accords with the convexity principle (7), which states that the energy of stabilization upon addition of the first electron to an atomic or molecular system (-AGO is greater than the stabilization energy attending addition of the second (-AG2). The converse set of conditions (-AG2 > -AGi, 2° > 1°, AGdisp < 0) may arise, however, when a change in structure or composition, e.g., ligation, protonation, ion-pair formation, accompanies electron transfer. This circumstance results in a multielectron event via an inversion of potentials and the destabilization of A". Numerous examples of such behavior have been identified and discussed 8-13),... 

In principle, one might try to study the ionic dissociation of an acid (equation 7.3) directly in the gas phase, but AH for dissociation of a neutral species to a proton and an anion is usually quite large without solvent stabilization of the ions. For example, the AH for the gas phase dissociation of methane to methyl anion and a proton (AH° jj) was calculated to be - -417kcal/mol. This is much greater than the homolytic C—H bond dissociation energy of methane (-I-104 kcal/mol), so thermolysis of methane in the gas phase leads to radicals instead of ions. The pKg value of an acid can be determined indirectly, however, by measuring the equilibrium for proton transfer from the acid to a base with a known pKg. With a series of measurements, a scale of gas phase acidity values can be established by referencing one compound to another. 

The principles outlined above are, of course, important in electro-synthetic reactions. The pH of the electrolysis medium, however, also affects the occurrence and rate of proton transfers which follow the primary electron transfer and hence determine the stability of electrode intermediates to chemical reactions of further oxidation or reduction. These factors are well illustrated by the reduction at a mercury cathode of aryl alkyl ketones (Zuman et al., 1968). In acidic solution the ketone is protonated and reduces readily to a radical which may be reduced further only at more negative potentials. 

Tautomeric equilibrium in aqueous cw-malonaldehyde, see reaction 1 in Figure 8-4, is a prototypical reaction extensively studied in the gas phase but still relatively unknown in solution. In fact, despite the large number of NMR experiments [52,53,54] and quantum chemical calculations [55] with the polarized continuum model (PCM), [1] the actual stability of czT-malonaldehyde is not well clarified, although the trans isomer should be the predominant form in water. Secondly, the involvement of the light proton in the reaction may in principle provide relevant quantum effects even in condensed phase. All these complications did not prevent this reaction to be used as a prototypical system for theoretical studies of intramolecular proton transfer in condensed phase by several investigators [56,57,58,59,60] including ourselves. 

This principle can be extended to ketones whose enolates have less dramatic differences in stability. We said in Chapter 21 that, since enols and enolates are alkenes, the more substituents they carry the more stable they are. So, in principle, even additional alkyl groups can control enolate formation under thermodynamic control. Formation of the more stable enolate requires a mechanism for equilibration between the two enolates, and this must be proton transfer. If a proton source is available— and this can even be just excess ketone—an equilibrium mixture of the two enolates will form. The composition of this equilibium mixture depends very much on the ketone but, with 2-phenylcyclo-hexanone, conjugation ensures that only one enolate forms. The base is potassium hydride it s strong, but small, and can be used under conditions that permit enolate equilibration. 

Most of the principles used to explain the acidity of compounds are also used to explain the reactivity and stability of organic compounds in general. Also, proton transfer reactions are often the first step in most organic reactions. For this reason, if we can thoroughly comprehend proton transfer, then we have a solid basis for understanding most organic reactions. 

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