Basicity aminopyridines

The structure of malonyl-a-aminopyridine (cf. 121) has been discussed by Snyder and Robinson/ who interpreted the infrared and ultraviolet spectra and the fact that it could be converted into a monochloro derivative (122, R = Cl) to indicate that the intra-molecularly hydrogen-bonded hydroxy form 122 (R = OH) was predominant. However, comparison of the basicities of the methoxy compound 122 (R = OMe), the mesomeric betaine 123 (R = Me), and the parent compound indicates that in aqueous solution the last exists mainly in the zwitterion form 123 (R = H), ... 

In their acidity, basicity, and the directive influence exerted on electrophilic substitution reactions in benzenoid nuclei, acylamino groups show properties which are intermediate between those of free amino and hydroxyl groups, and, therefore, it is at first surprising to find that the tautomeric behavior of acylaminopyridines closely resembles that of the aminopyridines instead of being intermediate between that of the amino- and hydroxy-pyridines. The basicities of the acylaminopyridines are, indeed, closer to those of the methoxy-pyridines than to those of the aminopyridines, the position of the tautomeric equilibrium being determined by the fact that the acyl-iminopyridones are strong bases like the iminopyridones and unlike the pyridones themselves. Thus, relative to the conversion of an... 

The 4-aminopyridine-type resonance, one of the most interesting methods by which hydration is facilitated, is illustrated by the small resonance in the neutral species of 4-aminopyridine (34) and the far greater resonance in the cation of the same substance (35). 4-Amino-pyridine owes its strongly basic properties (pA 9.2, as compared to... 

This may be rationalized from a consideration of resonance in the conjngate acids. The conjngate acids from ring protonation benefit from charge delocalization, which is greater in 4-aminopyridininm that in 2-aminopyridinium. This type of delocalization is not possible in 3-aminopyridinium 3-aminopyridine (p Ta 6.0) is the weakest base of the three aminopy-ridines, and has basicity more comparable to that of pyridine (pATa 5.2). 

This scheme eliminates the process of converting bis(etherimide)s to bis(ether anhydride)s. When polyetherimides are fusible the polymerization is performed in the melt, allowing the monamine to distill off. It is advantageous if the amino groups of diamines are more basic or nucleophilic than the by-product monoamine. Bisimides derived from heteroaromatic amines such as 2-aminopyridine are readily exchanged by common aromatic diamines (68,69). High molecular weight polyetherimides have been synthesized from various IV,IV-bis(heteroaryl)bis(etherimide)s. 

Hill and Morallee (121,122) recorded the proton NMR spectra of a series of bis-pyridinoiron (III) complexes. The compounds differed in the substituents at the ring positions 3 or 4 of the axial ligands, and the basicity of these ligands was thus varied from pKa = 1.9 in 4-cyanopyridine to pKa = 9.2 in 4-aminopyridine. In CD3OD at ca. 200°K all these complexes were found to be in the low spin forms, and it was observed that... 

The functionality at the vicinal positions of obtained aminopyridines 41o-r is useful for synthesis of [c]-fused bicyclic pyridines. For example, aminopy-ridine 41o undergoes the intramolecular nucleophilic substitution under basic conditions to give bicyclic pyridine 43 in a quantitative yield (Scheme 16). 

Under conditions of high temperatures the intermediate anion can re-aromatise by loss of a hydride ion, even though it is a very poor leaving group. This is illustrated by the Chichibabin reaction of pyridine and sodamide to produce 2-aminopyridine 5.26. The immediate product of the reaction is 5.27, the sodium salt of 5.26, as the eliminated hydride ion is very basic. Protonation of this sodium salt during the aqueous workup then regenerates 5.26. A simplistic rationale is shown below. 

The pKj of the aminopyridines attached to the polymer (Table 3.3) are invariably lower than those of the corresponding isolated small molecules. The cationic character of polyethylenimine produces an electrostatic field that weakens the basicity of the nucleophile by 2-3 pK units. A lowering of an additional unit ocurrs when a long apolar group is attached to the aminopyridine moiety. Evidently, in this molecule the apolar environment favors further the uncharged, nonprotonated form of the pyridine. 

Chlorination of 2-aminopyridine gives 5-chloro and 3,5-dichloro derivatives in equal amounts when the medium is 17 wt% H2S04, but 98 and 6%, respectively, in 72 wt% H2S04. This selectivity was ascribed to differences in rates of chlorination of protonated versus nonprotonated species (76JOC93). For the more basic 2-aminopyridine chlorination presumably occurs on the monocation throughout the acidity region but the less basic 5-chloro derivative chlorinates via the free base at low acidity. 

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