Pyridine derivatives from pyrylium

Nucleophilic addition at the 2-position of pyrylium salts (223) occurs readily under mild conditions and when ammonia or primary amines are used the subsequent ring-opening/ring-closure sequences give pyridines (224) and pyridinium salts (222), respectively (Section 3.2.1.6.4.iii). The process is most useful for the synthesis of 2,4,6-trisubstituted pyridine derivatives. Thiinium salts (226) are conveniently prepared from pyrylium salts (225) by treatment with sodium sulfide (Section 3.2.1.6.5), Thiinium salts (226) react with ammonia and amines similarly to their pyrylium analogues. 

Quite interestingly, the hydrazido(2-) Hgands derived from the ligating N2 in complexes 1 and 2 are transformed into N-hetero cyclic compounds by application of the condensation and related methods (Scheme 6). Thus, their reactions with 2,5-dimethoxytetrahydrofuran, pyrylium salts, and phthalaldehyde, followed by workup of the complexes containing N-heterocyclic ligands with LiAlH4 or KOH/alcohol, result in the formation of pyrroles [29], pyridines [30], and phthalimidines [31], respectively. 

Improved procedures for the Chichibabin amination of pyridine derivatives have been reported (83JAP(K)58-208266, 83USP4386209, 83USP4405790). A general method has been developed for the conversion of 2-aminopyri-dines into 2-pyridones via 2-cthoxycarbonyl-l-(2-pyridyl)pyridinium ions 15. The pyridinium ions 15 are easily made from the 2-aminopyridines 14 and the corresponding pyrylium salt 13. On treatment with aqueous sodium hydroxide, pyridinium ions 15 are converted into the l-(substituted-2-pyridyl-carbonyl)-2-pyridones 16, which are readily hydrolyzed to the 2-pyridones 17 and the picolinic acid 18 (83JCS(P1)2623). 

This includes heteroannulenes, which comply with the HUCKEL rule, i.e. which possess An + 2) -electrons delocalized over the ring. The most important group of these compounds derives from [6]annulene (benzene). They are known as heteroarenes, e.g. furan, thiophene, pyrrole, pyridine, and the pyrylium and thiinium ions. As regards stability and reactivity, they can be compared to the corresponding benzenoid compounds [1]. 

As in the synthesis of other bipyridines, several routes to 4,4 -bipyridine have been devised where one of the pyridine rings is built up from simpler components. For example, a dimer of acrolein reacts with ammonia and methanol in the presence of boron phosphate catalyst at 350°C to give a mixture of products including 4,4 -bipyridine (3.4% yield), and in a reaction akin to ones referred to with other bipyridines, 4-vinylpyridine reacts with substituted oxazoles in the presence of acid to give substituted 4,4 -bipyridines. ° ° Condensation of isonicotinaldehyde with acetaldehyde and ammonia at high temperatures in the presence of a catalyst also affords some 4,4 -bipyridine, and related processes give similar results,whereas pyran derivatives can be converted to 4,4 -bipyridine (56% conversion), for example, by reaction with ammonia and air at 350°C with a nickel-alumina catalyst. Likewise, 2,6-diphenyl-4-(4-pyridyl)pyrylium salts afford 2,6-... 

Of course, with atoms from lower periods of the periodic system, such as P or S, it is possible to have aromatic systems that are not simply homologs of pyridine or pyrylium, (i.e., phosphinine and thiopyrylium, respectively) but also systems with P(V) and S(IV), i.e. phosphabenzene (/. -phosphinine) and thiabenzene, respectively. However, in some cases the aromaticity is strongly perturbed, as for instance in selenabenzene derivatives stabilized by electron-withdrawing groups, when these compounds are shown to be zwitterionic. 

Both D-threo-2,5-hexodiulose (7) and kojic acid (10) afford the pyrido[l,2-a]quinoxaline 11 on treatment with o-phenylenediamine. The pathway via 8 and 9 explains the formation of the tricyclic compound from the hexodiulose. The product 11 forms the N-benzenesulfonate 12 on reaction with benzenesulfonyl chloride. Treatment with acetic anhydride in pyridine gives the diacetyl derivative 13. Quinoxaline-2-carboxylic acid is produced when 11 is oxidized with potassium permanganate. The condensation of o-phenylenediamine with the pyrylium salt 14 affords the pyridoquinoxalinium salt 16 by way of the intermediate N-phenylpyridinium salt 15. ... 

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