Effects on Amine Basicity

Potential-energy diagram of the base-dissociation reaction of an amine. 

Any structural feature that stabilizes the ammonium ion (relative to the free amine) shifts the reaction toward the right, making the amine a stronger base. Any feature that stabilizes the free amine (relative to the ammonium ion) shifts the reaction toward the left, making the amine a weaker base. 

Aniline is stabilized by overlap of the lone pair with the aromatic ring. No such overlap is possible in the anilinium ion. 

Resonance effects also influence the basicity of pyrrole. Pyrrole is a very weak base, with a of about 15. As we saw in Chapter 15, pyrrole is aromatic because the nonbonding electrons on nitrogen are located in a p orbital, where they contribute to the aromatic sextet. When the pyrrole nitrogen is protonated, pyrrole loses its aromatic stabilization. Therefore, protonation on nitrogen is unfavorable, and pyrrole is a very weak base. 

Hybridization Effects Our study of terminal alkynes (Section 9-6) showed that electrons are held more tightly by orbitals with more s character. This principle helps to explain why unsaturated amines tend to be weaker bases than simple aliphatic amines. In pyridine, for example, the nonbonding electrons occupy an sp orbital, with greater s character and more tightly held electrons than those in the sp orbital of an aliphatic amine. Pyridine s nonbonding electrons are less available for bonding to a proton. Pyridine does not lose its aromaticity on protonation, however, and it is a much stronger base than pyrrole. 

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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. 

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). 

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 results obtained with different amines cannot be explained merely on the effects of amine basicity. Thus, to obtain complete hydrogenation of Q to DHQ, the basicity has to be tailored by other factors such as the steric hindrance of the amine and its electronic interaction with the catalyst active sites this seems to be favored by the presence of an electron-rich aromatic ring. Of note, the positive effect of substituted aromatic amines, with a 49% DHQ yield being obtained for ethylanilines, is independent of the substituent position of the alkyl group. 

Table II. Effect of Amine Basicity on Product Distribution ...

The above discussion has shown that the effects of amine basicity and concentration on catalytic activity are consistent with Equilibrium 3. No explanation has been presented for the increased hydrogenation activity of species II as compared with the amine-free hydrido carbonyl (species III). The data in Table IV and the first-order dependence of aldehyde provide the basis for such an explanation. 

The base strengths of simple alkanamines usually are around Kb = 10-4 (Ka = 10-10) in water solution, and vary within perhaps a factor of 10 from ammonia to primary, secondary, and tertiary amines, as can be seen from the data in Table 23-1. Cyclohexanamine has about the same base strength as methanamine, whereas the effect on the basic nitrogen of being in a saturated ring, as in azacyclohexane, increases the base strength somewhat. 

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. 

In conclusion, the use of amines for the characterization of adsorption and active sites raises the same problems as ammonia. The interaction of the amines, saturated aliphatic amines in particular, with oxide surfaces is certainly still less specific than that of ammonia because of their higher basicity and their larger molecular size. The influence of steric effects on amine adsorption has been discussed (172, 201b). Thus, Medema et al. (172) came to the conclusion that the adsorbed amount of an amine on 7-Al2 03 primarily depends on its molec-... 

On the basis of gas phase and solution data from their own and several other laboratories Aue, Webb and Bowers published a paper in 1976 in which they were able to assess solvent effects on the basicities of amines in quantitative terms by applying the Born electrostatic model of solvation [25]. By separating the en-thalpic and entropic contributions, they noted that solvation attenuates gas... 

The apparent basicity anomaly of alkylamines can now be understood in terms of two opposing influences, one base-strengthening (due to increasing alkylation of the amine), and the other base-weakening (because of reduced solvation of the ammonium ions with increasing alkylation). For solvation effects on the basicities of alkyl amines in solvents other than water, see reference [243]. 

In contradiction with the results expressed before, we found that here the nature of the base is of little importance. However, to obtain good yields we were forced to use an excess of amines and it is known52) that NaNH2 is rather reactive in primary amines. Thus excess of primary amine must have a levelling effect on the basic power of NaNH2 and complex base. 

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.

As early as 1933 Kilpatrick and Kilpatrick [499] were able to compare the relative acid strengths of a number of compounds in acetonitrile (AN) and to compare that order with the order of the pK s in water. One of the first quantitative determinations was a study by H.K. Hall Jr. in 1957 [190] that examined steric effects on the basicities of cyclic amines in water and AN. This study yielded the pK s of 15 methyl piperidines and some related amines at 30 and 59.6°C, plus information on the thermodynamic parameters. Additional early acidity studies in AN were carried out by Kolthofl and his co-workers [500-502] and by Coetzee and Padmanabhan [503]. 

Lau, Y.K. and Kebarle, R (1981) Hydrogen bonding solvent effect on the basicity of primary amines CH3NH2, C2H5NH2, and CF3CH2NH2. Can. J. Chem., 59, 151-155. 

In simple aliphatic amines the number of alkyl groups attached to the nitro n has an effect on the basicity of the amine. Thus the order of basicity for amines is approximately secondary > primary > ammonia > tertiary. Hie increased basicity of primary and secondary amines over ammonia is due to the inductive release of electron density from the alkyl groups which increases the electron density on the nitrogen atom. This can be seen for the methyl-amines in Figure 3.5. 

Materials and additives that are chemically basic in nature have a detrimental effect on the curing of cationic-initiated epoxy systems. These substances can either stop the curing mechanism completely or produce under-cured polymers. Therefore such additives as amines or imides that are known to be adhesion promoters cannot be used in the EB-curable epoxy adhesive formulations. 

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