Pyridine quaternary amines

The general principle that activation of para substitution is greater than of ortho substitution holds true also for an azinium moiety in the one instance studied. Thus, the activation energy for the 4-chloropyridine quaternary salt 280 (Table II, line 9) is 1 kcal lower than that for the 2-isomer (line 5). The rate relation (2- > 4-isomer) is controlled by the entropies of activation in this reaction due to electrostatic attraction in the transition state (281). The reverse rate relation (4- > 2-position) is predicted for aminations of such quaternary compounds due to electrostatic repulsion (282) plus the difference in E. A kinetic study of the 2- and 4-pyridine quaternary salts... 

There are many combinations of surfactants reported. For example, cationic CTA surfactant and cationic Gemini surfactant, CTA and long-chain pyridine quaternary ammonium surfactant,11] anionic and cationic surfactant,1126 CTA and amine (Q2H25NH2), neutral and cationic surfactant,11761 and neutral-neutral surfactants have been used to prepare silica with interesting mesostructures (e.g., Ia3d cubic) or morphologies (e.g., nanoparticles). 

Species variations in the jt-methylatlon of pyridine have been reported by D Souza, et al. (31) Cats, gerblls, guinea pigs, and hamsters are EM, while humans, mice, rabbits, and rats are PM (Table I). The mouse, rabbit, and rat are, thus, good surrogates for man for amines. Since methylatlon to quaternary amines could represent an Intoxication step, experiments with EM would be more conservative. 

N-Methylation of pyridine-type nitrogen atoms (reaction 4, Fig. 13.15) seems to be of greater in vivo pharmacological significance than reactions 2 and 3 for two reasons. First, the resulting metabolites, being quaternary amines, are more stable than tertiary or secondary amines toward N-demethylation. And second these metabolites are also more polar... 

Figure 2.2 Types of nitrogen-containing functionalities on the carbon materials (a) pyrrole- like group (b) nitrile (c) secondary amine (d) nitro group (e) nitroso group (f) terciary (g) amine (h) pyridine-like group (i) imine (j) amide (k) lactam (1) pyri-done (m) quaternary amine.

Amination— The most characteristic reactions of alkyl groups attached to the pyridine nucleus would be expected, and are seen, to be electrophilic substitutions rather than amination. A reaction resulting in quaternary amination of the methyl group in 2-picoline 1-oxide has been mentioned (p. 210). Its mechanism has not been clarified. 

Initially, the research focused on the influence of temperature on bromination (position of the brome). In the next step, the brominated PPG was quaternary aminated by a mixture of amines (e.g., triethylamine [22], 4-vinyl-pyridine [182], or pyridine [183) or diamines (ethylenediamine [181) in order to cross-link. The highest lEC obtained was 3.5 X10 equiv./g. Gther hydroxyl-conducting membranes based on PPG were produced by Friedel-Crafts chloroacetylation and amination processes with trimethylarnine [184]. Under these conditions, an ion... 

B) Methiodi s. Members of Classes (i), (ii) and (iv) combine wdth methyl iodide (some very vigorously) to form quaternary methiodides. It is best to add the amine to an excess of methyl iodide dissolved in about twice its volume of methanol, allow any spontaneous reaction to subside, and then boil under reflux for 30 minutes (extend to 1 hour for Class (iv) except pyridine and quinoline). The methiodide may crystallise when the reaction-mixture cools if not, evaporate the latter to small bulk or to dryness, and recrystallise, (M.ps., pp. 553-554 )... 

The amination of 2-chloropyridine-A-oxide (53) with potassium amide in liquid ammonia yielded a mixture of 2-(55) and 3-amino-pyridine-A-oxide (56) in 5-10% total yield.This rearrangement might be explained by an aryne mechanism involving 2,3-pyridyne-A-oxide (54). Since the structure of 56, with its quaternary nitrogen atom, is more analogous to that of 3-methoxybenzyne (39) than to that of 2,3-pyridyne (26), an orientation effect directing the amide ion to C-3 can be expected here. 

The.effect of the entropy of activation was noted above for the quaternary pyridine salts (280 and 281). In future work, it may also be found to reflect the electrostatic or hydrogen-bonding interactions in transition states of amination reactions and the effect of reversible cationization of an azine-nitrogen. Brower et observed a substantial rate difference between piperidino-dechlorinations of 2-chloropyrimidine in petroleum ether and in alcohol due partly to the higher entropy of activation in the latter solvent (Table III, lines 3 and 4). 

Pyridine (and quinoline) which in so many respects are aromatic and comparable to benzene, lose this character completely on hydrogenation to piperidine (and hydroquinoline), which are entirely of the same nature as secondary aliphatic amines. The completely hydrogenated heterocyclic bases undergo degradation reactions which have become important particularly in the investigation of the constitution of alkaloids. A. W. Hofmann s method of opening rings by means of exhaustive methylation may be illustrated with piperidine. By thermal decomposition of the quaternary ammonium base a C—N-link-age is broken and at the same time water is eliminated. 

Piperidine is a secondary amine pK 11.3 cf. diethylamine, pK 11.0) it is more basic than pyridine pK 5.2). It is also a good nucleophile, and it is A-alkylated by alkyl halides in the presence of potassium carbonate to form first A-alkylpiperidines and then quaternary salts. 

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