On amine basicity

On studying a series of ammonium 1,3,2,5-dioxaborataphosphorinane oxides (111), the dependence of the tautomeric equilibrium position on amine basicity was analyzed. The equilibrium position was estimated from chemical shift values of bis(oxymethyl)phenylphosphine oxide with 8 3IP of 35 ppm being used as a model of an acyclic form and 5-Ph-5-oxo-1,3,5-dioxaphosphorinane (107, R = H) with 8 3IP of 6 ppm used as a model of a cyclic compound. The chemical shift values (111, X = 0, R = H) and dissociation constants (pKa) of conjugate acids for amines are presented in Table V. 

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 aldehyde hydrogenation reaction is strongly dependent on amine basicity. The data in Table I obtained with DMBA demonstrate... 

An early study of deuterium IEs on amine basicity found that the pAa of morphine-A-CD3 is 8.17, compared to 8.05 for morphine.48 Similarly, codeine-A-CD3 has a pAa of 8.19, higher than the 8.06 of codeine itself, and the pAa of PhCH2CD2NH2 is 9.18, whereas that of PhCH2CH2NH2 is 9.08. 

Secondary IEs on amine basicity were key to the feasibility of a study of the symmetry of hydrogen bonds in tetramethylnaphthalenediamines.54,55 Because the presence of impurities could explain both the need to revise the ApAa of... 

The data in Table 5 confirm that there are indeed secondary deuterium IEs on amine basicity, as had also been confirmed by data on glycine, alanine, A-methyl-4-fluoroaniline, and N,N-dimethyl-4-fluoroaniline obtained by... 

The IEs on amine basicity are also due to changes in vibrational frequencies, not only computationally but also experimentally. Gas-phase IEs of O.lOkcalmol-1 per CD3 group on basicities of methylamine, dimethy-lamine, and trimethylamine can be reproduced by ab initio force constants for C-H stretching, which increase on TV-protonation.100 Infrared spectra of amines show characteristic bands (called Bohlmann bands ) in the 2700-2800 cm-1 region, lower than the 2900 cm-1 of a typical C-H stretch.169,170 Upon /V-protonation these bands revert to a typical, higher frequency. Therefore the zero-point energy of the C-H increases on... 

Evidence against an inductive contribution comes from experimental IEs on amine basicity. According to Equation (28), there is no angle-independent term. This is the term that would arise from an electrostatic interaction between a positive charge on the N and a C-H or C-D bond dipole.3 Although Equation (28) is imperfect, and there are smaller IEs from synperiplanar C-D, we conclude that an inductive effect is too small to contribute to the observed IE. 

Moreover, the inductive contribution of a p deuterium to the IE on amine basicity was estimated.31 The inductive effect on pK due to an sp2-sp3 C-C bond, with a dipole moment of 0.35 D, as in propene, can be assigned as 0.95, the ApAf between allylamine and methylamine. Above, in connection with the structural question of the extent to which IEs affect dipole moments, dCu dco is 0.5 pm and dfi/dd is 0.004e. These combine to a ApAT on deuteration of 0.001, which is much smaller than the measured IEs in Table 5. An inductive contribution does exist, but it is negligible. 

N-Acylimidazoles (azolides) have continued to provide a synthetic source of acid derivatives,and the various olysis reactions of these compounds have been studied. " The reactions of acetyl-imidazolium ions with amines have been found to depend largely on amine basic) The thermal decarboxylation of JV-alkoxycarbonylimid-... 

Apart from ammonium derived hydroxide, few onium salts have been used as supported bases. However, an analog of Hunig s base was prepared and employed as a catalyst in Knoevenagel condensations [68], Increase in the linker length was found critical to observe a good activity, as cation effect on amine basicity can be detrimental for short alkyl chains. Finally, using a biphasic liquid-liquid mixture, no significant decrease in activity has been noticed after five cycles (Fig. 25). 

Figure 3.6 Effect of hydroxyl epimerisation. Top, relative rates of hydrolysis of 2,4-dinitrophenylglycosides, taken from Ref. 28 or extrapolated from Ref 29 Bottom, effects of hydroxyl epimerisation in the isofagomine skeleton on amine basicity, taken from Ref. 37.

Alder, R.W. (1989) Strain effects on amine basicities. Chemical Reviews, 89, 1215-1223. 

Staab, H.A. and Saupe, T. (1988) Proton sponges and the geometry of hydrogen bonds aromatic nitrogen bases with exceptional basicities. Angewandte Chemie - International Edition, 27,865-879 Alder, R.W. (1989) Strain effects on amine basicities. Chemical Reviews, 89,1215-1223. 

C.L. Perrin and his students have measured [3-deuterium secondary isotope effects on amine basicities and found that deuteration increases the basicities of the compounds investigated [552]. The effect is attributed to a lowering of the ZPE of a C-H bond adjacent to an amine nitrogen. The Perrin group has also applied the same techniques to carboxylic acids and phenols [553], andpyridines [554]. 

Stereochemistry of -deuterium isotope effects on amine basicity, J. Am. Chem. Soc. 127 (2005), pp. 9641-9647. 

The large slopes (a = 0.7-1.0) indicate a very strong dependence of kx on amine basicity, and considerable carbon-nitrogen bond formation in the transition states. These results suggest a hard character for the dienyl rings in cations 20 (M = Fe) and 25. 

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