Proton affinity, and basicity

Within a molecular orbital approximation, the electron is ejected from the highest occupied molecular orbital (HOMO). Molecular orbital calculations at various levels of sophistication describe the highest occupied MOs of most yhdes as being strongly localized on tlie ylidic carbon. Exceptions to this are found for example in cyclopentadienide derivatives, where the orbital of corresponding symmetry is the HOMO-1 (IE2). In terms of reactivity, the low first ionization potentials of ylides reflect high oxidizabihty, high proton affinity, and basicity. UV photoelectron spectra in conjunction with detailed molecular orbital calculations for each individual ylide structure have made possible a rationalization of the different substituent and heteroatom effects. 

E. P. L. Hunter, S. G. Lias., Evaluated gas phase basicities and proton affinities of molecules An Update. J. Phys. Chem. Rtf. Data, 1998, 27,413 E. P. L. Hunter, S. G. Lias., Proton Affinity and Basicity Data, in NIST Chemistry Web Book, Standard Reference Database, 2005, No. 69 (eds W. G. MaUard and P. J. Linstrom), National Institutes of Standards and Technology, Gaithersburg, MD (http // webbook.nisLgov/chemistry, accessed May 2012). 

Parthaserathi et al. [238] have used the group philicity index to estimate the pK s of several phosphoric acid esters and related compounds They included the calculations in a group with anilines and alcohols, but the numerical results for the phosphoric acids appear generally good Moser, Range, and York [301] have calculated gas-phase proton affinities and basicities for a large collection of acyclic and cyclic phosphates. 

These compounds can be present in a variety of tautomeric forms both in the gas phase and in solution, and the presence of the proper form is normally crucial for each biological role being played, as for example, in stabilizing the double helix of DNA. Indeed, it was insight into the correct tautomeric forms of the DNA bases that was critical for the discovery of the DNA double-helix structure [376,377], Moser, Range, and York [301] have provided high-level benchmark calculations of the gas-phase proton affinities and basicities for many of the tautomers of these compounds. A number of additional studies have addressed the tautomeric equilibria of these compounds in both gas and aqueous phases [378-382]. 

C. Matijssen, G.K. Kinsella, G.W. Watson, and I. Rozas, Computational study of the proton affinity and basicity of structurally diverse al-adrenoceptor ligands, J. Phys. Organic Chem. 25 (2012), pp. 351-360. 

There is a large array of cations that have been studied in the gas phase for their interaction with Lewis bases (generally neutral organic molecules) and are still being actively investigated today. The most studied is the proton [1-6]. This special cation will not be dealt with in this chapter (however, see Section 1.3 in Chapter 1), since the proton and its transfer serve to define the Bronsted acids and bases, as opposed to Lewis acids and bases, which do not exchange protons. Moreover, although the proton and a cation with an empty orbital may be seen as identical from the point of view of the Lewis theory, the special electronic structure of the proton (in fact the absence of any electron) makes the proton affinity and basicity scales completely different, qualitatively and quantitatively, from any other cation scales. 

Dixon, D.A. and Lias, S.G. (1987) Absolute values of gas phase proton affinities and basicities of molecules a comparison between theory and experiment. Mol. Struct. Energ., 2, 269-314. 

The values for proton affinity and basicity listed are for a temperature of 298 K. For some specific molecules, such as H2O, CO2 and ethane, there is a considerable array of experimental and theoretical data to justify an estimated error margin of 1-3 kj mol . For most other molecules the error margins are somewhat larger, with Hunter and Lias estimating a... 

However, in more complicated amines, this straight correlation is violated. The bicyclic tertiary amine l-azabicyclo[4.4.4]tetradecane (22) and the acyclic tertiary amine n-Bu3N have nearly the same first IP (7.84 and 7.90 eV, respectively), but the proton affinity of the bicyclic amine is 20 kcal mol 1 lower than that of the acyclic52. On the other hand, for other bridge-head tertiary amines like l-azabicyclo[2.2.2]octane (quinuclidine, 20) and l-azabicyclo[3.3.3]undecane (manxine, 21) the expected relation between proton affinities and IP values is observed. The extraordinary properties of l-azabicyclo[4.4.4]tetradecane (22) are caused by its unusual conformation the nitrogen lone-pair is directed inward into the bicycle where protonation is not possible. In the protonated form, the strained out-conformation is adopted. This makes it the least basic known tertiary amine with purely saturated alkyl substituents. Its pKa, measured in ethanol/water, is only +0.693. Strain effects on amine basicities have been reviewed by Alder88. 

Proton affinity and gas phase basicity are thermodynamic quantities. Consider the following gas phase reaction of a (basic) molecule, B ... 

Table 2.6. Selected proton affinities and gas phase basicities [28,100,110]...

The intrinsic basicities of cyclopentenone and cyclohexenone (59), and their lactone analogues (60), have been accessed via measurement of their gas-phase proton affinities, and compared with the saturated carbonyl compounds in both cases. The results... 

Proton Affinities and Intrinsic Basicities of Azole Anions ... 

Nucleophilicity. A distinction is usually made between nucleophilicity and Lowry-Bronsted basicity [213]. The latter involves specifically reaction at a proton which is complexed to a Lewis base (usually H2O), while the former refers to reactivity at centers other than H. Linear correlations have been shown for gas-phase basicity (proton affinity) and nucleophilicity of nitrogen bases toward CH3I in solution [214] where the solvent is not strongly involved in charge dispersal. In each case, reaction of the base/nucleophile... 

In Section IV-VI we systematically discuss the acidity, basicity and, where appropriate, the hydrogen-bonding of nitrones, nitriles and thiocarbonyls. Since this review very much relies on physical measurements and the discussion of acid-base reactions, Section HI provides a brief introduction to proton affinity and a short summary of the acid-base concept and the quantitative measure of basicity. 

The proton affinity and acidity of uracil itself (2a) has also been the subject of computational investigation, primarily by the groups of Zeegers-Huyskens and Lee.52-57 Lee and coworkers have also conducted a series of experimental investigations that have established that uracil has four sites that are more acidic than water (Nl, N3, C5, and C6) and that 04 is 8 kcal mol-1 more basic than 0254-56 Gronert and coworkers also conducted clever mass spectrometric experiments that effected decarboxylation of orotate to form the C6-deprotonated uracil (3a), which was then used to measure the acidity of the C6-H.57,58a Gronert s calculations and experiments, later confirmed by Lee and Kurinovich using different uracil derivatives,55 established that the C6 site of uracil is quite acidic with a gas phase acidity (A//acid) of —369 kcal mol-1, this site is as acidic as acetone. Recent experiments in water, however, indicate that the C6-H of 1,3-dimethyl uracil has a pK of 34, considerably less acidic than that of acetone (pA a — 19).58b... 

The general strategy for generating radical adducts to heterocyclic molecules relies on selective protonation of a suitable neutral precursor to prepare a cation of a well-defined structure. The gas-phase acid is chosen so as to attack only the most basic site in the molecule, or alternatively, non-selective protonation can be used to prepare a mixture of ions. For example, protonation of imidazole with NH4+ occurs selectively on the imine nitrogen atom (N-l), which has the highest proton affinity and is the only position that can be protonated by an exothermic reaction (Scheme 22) [239]. 

TABLE 14. Gas phase basicities, proton affinities and hydride affinities for cations... 

In order to understand the difference in basicity, proton affinity and stability of complexes of N, on the one hand, and As, Sb and Bi on the other, we discuss the stability of ammonium vs arsonium chloride. Using a simple Bom-Haber approach as described in Reference 34 we can estimate the heat of reactions 28-31 AH°) as summarized in Table 1. All data were estimated as illustrated in Schemes 1-5. 

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