Proton transfer, and acidity

The extension of analytical mass spectrometry from electron ionization (El) to chemical ionization (Cl) and then to the ion desorption (probably more correctly ion desolvation ) techniques terminating with ES, represents not only an increase of analytical capabilities, but also a broadening of the chemical horizon for the analytical mass spectrometrist. While Cl introduced the necessity for understanding ion—molecule reactions, such as proton transfer and acidities and basicities, the desolvation techniques bring the mass spectrometrist in touch with ions in solution, ion-ligand complexes, and intermediate states of ion solvation in the gas phase. Gas-phase ion chemistry can play a key role in this new interdisciplinary integration. 

Tsutsumi, K., Shizuka, H., "Proton Transfer and Acidity Constant in the Excited State of Naphthols by Dynamic Analyses," Z. Phys. Chem., 1980, 122,129. 

All spectroscopic lines have a natural line width, and this can be of great use to the kineticist. This natural line width is determined by the lifetime of the excited state of the molecule. If this is short the line width is broad, while longer lifetimes give more sharply defined lines. If reaction occurs, this can alter the lifetime of the excited state and so change the natural line width of the transition. A detailed spectroscopic analysis gives relations between the width of the line, the lifetime of the reacting species and the rate constant for the reaction. This has proved a very important tool, especially for reactions in solution such as proton transfers and acid/base ionization processes. 

Many organic reactions involve proton transfer, and acid-catalyzed or base-catalyzed reactions may be the "largest single class of organic mechanisms." We will not attempt to survey all possible acid-catalyzed and base-catalyzed reactions. Instead, we will first develop some ideas about how proton transfers are involved in organic reactions and then use these... 

These equations tell us that the reverse process proton transfer from acids to bicarbon ate to form carbon dioxide will be favorable when of the acid exceeds 4 3 X 10 (pK, < 6 4) Among compounds containing carbon hydrogen and oxygen only car boxylic acids are acidic enough to meet this requirement They dissolve m aqueous sodium bicarbonate with the evolution of carbon dioxide This behavior is the basis of a qualitative test for carboxylic acids... 

Notice that specific acid catalysis describes a situation in which the reactant is in equilibrium with regard to proton transfer, and proton transfer is not rate-determining. On the other hand, each case that leads to general acid catalysis involves proton transfer in the rate-determining step. Because of these differences, the study of rates as a function of pH and buffer concentrations can permit conclusions about the nature of proton-transfer processes and their relationship to the rate-determining step in a reaction. 

There is an intermediate mechanism between these extremes. This is a general acid catalysis in which the proton transfer and the C—O bond rupture occur as a concerted process. The concerted process need not be perfectly synchronous that is, proton transfer might be more complete at the transition state than C—O rupture, or vice versa. These ideas are represented in a three-dimensional energy diagram in Fig. 8.1. 

Step 1 of Figure 29.14 Transimination The first step in transamination is trans-imination—the reaction of the PLP—enzyme imine with an a-amino acid to give a PLP—amino acid imine plus expelled enzyme as the leaving group. The reaction occurs by nucleophilic addition of the amino acid -NH2 group to the C=N bond of the PLP imine, much as an amine adds to the C=0 bond of a ketone or aldehyde in a nucleophilic addition reaction (Section 19.8). The pro-tonated diamine intermediate undergoes a proton transfer and expels the lysine amino group in the enzyme to complete the step. 

The picture shows that H has moved from nitric acid to water, forming a cation and leaving behind an anion. The process is proton transfer, and electrical charge is conserved. 

Because the breadth of chemical behavior can be bewildering in its complexity, chemists search for general ways to organize chemical reactivity patterns. Two familiar patterns are Br< )nsted acid-base (proton transfer) and oxidation-reduction (electron transfer) reactions. A related pattern of reactivity can be viewed as the donation of a pair of electrons to form a new bond. One example is the reaction between gaseous ammonia and trimethyl boron, in which the ammonia molecule uses its nonbonding pair of electrons to form a bond between nitrogen and boron ... 

Both these methods require equilibrium constants for the microscopic rate determining step, and a detailed mechanism for the reaction. The approaches can be illustrated by base and acid-catalyzed carbonyl hydration. For the base-catalyzed process, the most general mechanism is written as general base catalysis by hydroxide in the case of a relatively unreactive carbonyl compound, the proton transfer is probably complete at the transition state so that the reaction is in effect a simple addition of hydroxide. By MMT this is treated as a two-dimensional reaction proton transfer and C-0 bond formation, and requires two intrinsic barriers, for proton transfer and for C-0 bond formation. By NBT this is a three-dimensional reaction proton transfer, C-0 bond formation, and geometry change at carbon, and all three are taken as having no barrier. 

Proton Transfer and Electron Transfer Equilibria. The experimental determination used for the data discussed in the above subsections of Section IV.B were obtained from ion-molecule association (clustering) equilibria, for example equation 9. A vast amount of thermochemical data such as gas-phase acidities and basicities have been obtained by conventional gas-phase techniques from proton transfer equilibria,3,7-12-87d 87g while electron affinities88 and ionization energies89 have been obtained from electron transfer equilibria. 

However, the formation of intermediate 14 requires at least two steps, (i) a proton transfer and (ii) the formation of the cyclic intermediate. If formation of the intermediate, 14, is rate-determining, the carboxy hydrogen must be lost in a pre-equilibrium step because no deuterium kinetic isotope effect is observed for this reaction (Scheme 34). Alternatively, the mandelic acid could displace an acetate ligand in a slow step and the proton could be transferred to the acetate ion in a fast, subsequent step (Scheme 35). Unfortunately, the results do not indicate which step in the formation of the cyclic intermediate, 14, is rate-determining. 

Acid and base catalysis of a chemical reaction involves the assistance by acid or base of a particular proton-transfer step in the reaction. Many enzyme catalysed reactions involve proton transfer from an oxygen or nitrogen centre at some stage in the mechanism, and often the role of the enzyme is to facilitate a proton transfer by acid or base catalysis. Proton transfer at one site in the substrate assists formation and/or rupture of chemical bonds at another site in the substrate. To understand these complex processes, it is necessary to understand the individual proton-transfer steps. The fundamental theory of simple proton transfers between oxygen and nitrogen acids and... 

The existence of chain transfer in ionic polymerizations was first found in the system isobutene-BFj at room temperature when it was discovered that very small traces of water, tert-butanol, or acetic acid would, as co-catalysts, cause the transformation of large quantities of monomer to very low unsaturated polymers [2, 5]. It was assumed that the process involved proton transfer, and there is no cause to change this view ... 

In 1923 the American chemist G.N. Lewis provided a broad definition of acids and bases, which covered acid-base reactions not involving the traditional proton transfer an acid is an electron-pair acceptor (Lewis acid) and a base is an electron-pair donor (Lewis base). The concept was extended to metal-ligand interactions with the ligand acting as donor, or Lewis base, and the metal ion as acceptor, or Lewis acid. 

Usually, proton transfer in acid-base equilibria is a fast process, but very hindered systems show slow kinetics. The equilibrium (equation 3) regarding 2,4-dialkylpyridines proceeds through locked-rotor and with intermediates of low entropy44. 

Figure 2.4 Carboxylic acid dimer in the potential energy minima with local vibrational states. OV represents the correlation time for a thermally activated proton transfer, and TU, the correlation time for tunneling transfer. (Reproduced with permission from ref. 29.)...

Marincean and Jackson [38] have performed MP2//6-311-I-I-G calculations for proton transfer from acids H2O, HF, and HCl to ions [AlHj]" to form covalent-bonded products after H2 elimination ... 

The interaction of alkali salts with inorganic and organic acids has been extensively studied by the same group. In the case of alkali fluorides it was shown that milling leads to proton transfer and to formation of KHF2, while the reactivity of fluorides follows the order KF>NH4F>NaF>LiF, Cap2 [71b,c]. 

Consequently, the processes most relevant to the topic of this chapter, that is, hydrogen bonds in organocatalytic transition states, are (i) transition state stabilization by pure hydrogen bonding (without full proton transfer), and (ii) general Bronsted-acid/Bronsted-based catalyzed reactions which are initiated by hydrogen bonding but move further to distinct proton transfer. 

---