Proton affinities substituent effects

The reactivities of carbenes toward alkenes have been correlated with the inductive and resonance effects of the carbene substituents, log k — a Eat + fcEaR+ + c.m Analogous correlations cannot be obtained for the reaction rates of carbenes with alcohols, neither with the substituent parameters used by Moss,109 nor with related sets.110 In particular, the substituent parameters do not describe the strong, rate-enhancing effect of aryl groups. For a detailed analysis, see the discussion of proton affinities (Section V.A). 

It is well known that alkyl substitution changes the basicity of amines. However, solvation effects lead to an anomalous order of basicities in solution (NH3 tertiary amine < primary amine < secondary amine). From gas-phase proton affinity data the intrinsic effects of alkyl substituents can be evaluated and a quite regular order (NH3 < primary amine < secondary amine < tertiary amine) is obtained91. 

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. 

The proton affinity results reflect changes in polarizability and inductive effects with the substituent group R. Comparison of proton affinities in the nitrile and primary amine series (Figure 10) reveals that the magnitude of these effects is linearly related in the two series but larger for the nitriles. A least-squares fit to the data is given by equation 26... 

Another important question related to substituent effects on gas-phase basicities of thiocarbonyl compounds is whether these substituent effects arise from interactions within the neutral or within the protonated species, or both. It is useful to define the relative proton affinities along the monosubstituted series of compounds by means of the process shown in equation 54. 

These calculations show that (i) the methyl affinities (MeAs) of C=S compounds are consistently much higher (for X = H, 15 to 25 kcalmol-1 over the range Y = F to Y = NH2) than those of the C=0 homologs, and (ii) the sensitivity to substituent effects of the thiocarbonyls is ca 72% that of the carbonyls. Protonation and methylation therefore display the same pattern of structural effects (there is also a nearly perfect correlation between the PAs and MeAs for each family, although in all cases the PA exceeds the MeA by some 100 kcalmol-1). 

There appear to be few studies related to substituent effects on the properties of protonated carboxylic acid and related molecules. It has been found that the proton affinities of the saturated methyl esters increase with increasing chain length ( ) according to the equation (in units of kj mol-1)... 

Fig. 16. Correlation of substituent effects on gas-phase proton affinities of pyridines with the corresponding effects on aqueous heats of ionization (77JA5729).

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. 

One can see that there is only a slight difference between the N-substituents of the molecular structures 1 and 2. This indicates that this kind of substituent may strongly effect the proton affinity of the nitrogen atom and influence the N-H- O or O H- N types of H-bond interactions (Scheme 4). The only difference between the structures analyzed here, except for the intramolecular H-bond mentioned above, is the R4 substituent which is N(CH3)—P(0) (0C6H5)2 for 1 and NH-P(S)(OC6H5)2 for 2. 

Other structural studies by ICR include basicity of methylpyrazoles (13 compounds) <90JA1303> acid-base properties of trifluoromethylpyrazoles in the gas phase <9lJOC3942> the determination of the gas-phase proton affinities of 32 A-H and A -methyl pyrazoles and the analysis of these data by comparison with ab initio 6-3IG calculations <92JOC3938>. The gas-phase basicities of eight pyrazoles substituted only at position 4 (R = H, NO2, F, Cl, C02Et, CH3, NHj, 1-adamantyl) were measured and the experimental values discussed in two ways (i) by comparing these values with AMI calculated proton affinities and (ii) within the framework of the Taft-Topsom analysis of substituent effects <95JCS(P2)1875>. 

This effect was observed by Schlabach et al. [20] for an unsymmetrically substituted acetylporphyrin (AGP, Fig. 6.27, X=CH3CO) dissolved in CD2CI2. The thermodynamics and the kinetics of the HH, HD, DH and DD reactions could be studied by NMR. It was observed that the acetyl substituted pyrrole ring exhibits a smaller proton affinity as compared to the other pyrrole rings which are substituted with aliphatic substituents (Fig. 6.28(a)). The equilibrium constant was given by... 

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