Basic strength heterocyclic bases

In this section three main aspects will be considered. Firstly, the basic strengths of the principal heterocyclic systems under review and the effects of structural modification on this parameter will be discussed. For reference some pK values are collected in Table 3. Secondly, the position of protonation in these carbon-protonating systems will be considered. Thirdly, the reactivity aspects of protonation are mentioned. Protonation yields in most cases highly reactive electrophilic species. Under conditions in which both protonated and non-protonated base co-exist, polymerization frequently occurs. Further ipso protonation of substituted derivatives may induce rearrangement, and also the protonated heterocycles are found to be subject to ring-opening attack by nucleophilic reagents. 

A similar failure in the case of heterocyclic compounds is shown by the basicity of even heteroaromatic bases such as pyridine or quinoline. These all have similar basic strengths, as the simple PMO method predicts (Section IX). However the charge densities on the nitrogen atoms calculated51 by the Hiickel method are not the same (Table IV) application of Eq. (101) would then imply that the bases should differ considerably in strength. 

The effects of substituents on the acidic and basic strengths of imidazoles have been discussed by Hofmann1 and Pozharskii et al.3 in previous reviews. Precise data have been determined175 for the basicity of imidazole in D20-H20 mixtures. Perrin176 has developed methods based on the Hammett equation for predicting the pKa values in water of substituted imidazoles (and other heterocycles), while applications of the Hammett equation have also been made to 2-substituted imidazoles.177 Calculations of j>K values for 2-amino-imidazolium ions suggest that 2-aminoimidazoles are better regarded... 

The proton affinities (gas phase) of thiirane and other three-membered heterocycles have been determined azirane (902.5), thiirane (819.2), phosphirane (815.0), oxirane (793.3 kJ moF ) (80JA5151). Increasing s character in the lone electron pairs decreases proton affinities. Data derived from NMR chemical shifts in chloroform indicate the order of decreasing basicity is azirane > oxirane > thiirane (73CR(B)(276)335). The base strengths of four-, five- and six-membered cyclic sulfides are greater than that of thiirane. 

Table 24.1 lists pXa values of some ammonium ions and indicates that there is a substantial range of amine basicities. Most simple alkylainines are similar in their base strength, with p/q/s for their ammonium ions in the narrow range 10 to 11. Aiylctmines, however, are considerably less basic than alkylamines, as are the heterocyclic amines pyridine and pyurole. 

Like pyridine and imidazole, pyrrole is an aromatic heterocycle, but it is not nearly as basic as pyridine or imidazole. Pyrrole s lack of base strength can be understood by noticing that the lone pair on the nitrogen atom is in a 2p orbital and is part of the aromatic sextet of electrons. As a consequence, a protonated pyrrole cannot maintain aromaticity because the protonated nitrogen would be sp hybridized and there would be only 4 tt electrons remaining (in violation of two of Hiickel s aromaticity rules). A loss of aromaticity is energetically very costly and severely limits the ability of pyrrole to accept a proton despite its structural similarity to pyridine and imidazole. 

To verify that this is purely based on the hydrogen-bond strength of the donors and acceptors, it is important to establish whether the balance between an aromatic N-heterocycle and an amide can be reversed by lowering sufficiently the hydrogen-bond accepting property of the aromatic nitrogen atom. With this in mind, we synthesized a set of ditopic supramolecular reagents that combined an amide moiety with a very weak base, pyrazole. The idea was that if the basicity of the... 

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