Alkylpyridines amines

The results of some of the many aminations of pyridine and its derivatives that have been carried out appear in Table 14. Yields are quoted where possible but these should not be used for quantitative comparisons as reaction and work up conditions vary widely. 2-Alkylpyridines aminate at the vacant a-position, except when the substituent is very large. 2-f-Butylpyridine does not undergo the Chichibabin reaction, probably because the bulky 2-f-butyl group prevents adsorption on to the sodamide surface. In contrast, 2-phenylpyridine undergoes amination in very good yield. Aminations of 2- and 4-methyl-pyridines do not involve attack on the anhydrobases in aprotic solvents, but some ionization does take place in liquid ammonia. 4-Benzylpyridine forms a carbanion (148) which is only aminated with difficulty by a second mole of sodamide (equation 103). 

Alkylpyridines are aminated preferentially at the 2-position, but reaction is slower than in the parent system. Quinoline is difficult to aminate and only a low yield of 2-aminoquinoline (32%) is obtained from reaction with sodamide in toluene. When dimethylaniline is employed as solvent, 2-amino-3,4-dihydroquinoline (24%) becomes the major product, and the yield of 2-aminoquinoline drops to 7%. The best yields of 2-aminoquinoline (53-69%) have been obtained by using barium or potassium amide in liquid ammonia. Use of the potassium salt also produces a 10% yield of the 4-amino isomer. The... 

The study of pyridine-piperidine reactions under high pressure conditions has given much information concerning the kinetics of HDN, but these results are however complicated by alkyl transfer (disproportionation) reactions, and thus the possibility of using such reactions as an easy test for determination of mechanism and as a catalyst probe is partly excluded. The study of polycyclic amines (quinoline, etc.) for the same purpose is limited by the complexity and the number of different possible routes, but is a very interesting test reaction for an overall study of catalytic activity or selectivity toward HDN in industrial conditions. Because no disproportionation occurs and the numbers of products and routes are reasonable, the studies of pyridine-piperidine and alkylpyridine-alkylpiperidine HDN under normal H2 pressure and low amine pressure (< lOTorr) are very powerful test reactions both for mechanism determination and catalyst study, although these conditions are far removed from those of industrial practice. 

An enormous amount of work has been carried out on the amination of alkylpyridines, and the work has been well documented (42OR91 54CRV449 62HC(14,3)1 67MI1 74MI1). This section will cover the more recently reported aminopyridines. The amination products of some alkylpyridines are listed in Table V. 

The monomeric structural unit of the 3-alkylpiperidine alkaloids is readily apparent in a number of simple 3-alkylpyridines isolated from marine sponges. In all known examples, the 3-alkyl component of the monomeric unit is attached to a primary amine, methyl amine, methoxy amine, methoxy methyl amine, imine oxide or oxime methyl ether functionality at the distal terminus. 

Niphatynes A (1) and B (2) isolated from a Niphates sp. collected off Vitu Levu in the Fijian Islands were the first reported examples of monomeric 3-alkylpyridines from sponges [17]. These two metabolites, which contain the alkyne and methoxy amine functionalities encountered in many of the monomeric 3-alkylpyridines, were reported to be cytotoxic to murine leukemia P388 in vitro (niphatyne A (1) ED50 0.5 [ig/ml). Niphatesines A (3), B (4), C... 

Heteroaromatic amines react with alkylpyridines in the presence of sulfur to give the corresponding thioamides. For example, from 3-aminopyridazine, with 2-methylpyridine and sulfur, compound 219 is obtained. When, however, the 2-methylpyridine (or diethyl malonate) was used in catalytic amount, 3-aminopyridazine-5(2H)-thione (220) was obtained at 160°-170°C.474 Pyridazine-3-thiones react with a-halocarbonyl compounds to give the corresponding keto-sulfides, which can be further cyclized.475... 

More vigorous conditions are required for the amination of 2- or 4-alkylpyridines since proton abstraction from the side-chain by the amide occurs first and ring attack must therefore involve a dianionic intermediate. " Amination of 3-alkylpyridines is regioselective for the 2-position. ... 

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