Pyryliums ring synthesis

A formal and rather remote analogy to the method previously described for salts 30 can be seen in another C2 + C3 synthesis of the Cs-chain, which cyclizes to yield the pyrylium ring of l-aminobenzo[c]pyrylium bromide 80 (78JOC3817). 

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-... 

As discussed in Section 4.2.3.4.1, pentane-1,5-diones (200) can undergo ring closure to give a pyran (199) or, in the presence of ammonia, a dihydropyridine (201). Oxidative aromatization of these products occurs so easily that it frequently takes place prior to isolation, giving a pyrylium salt (198) or a pyridine (202). The Hantzsch dihydropyridine synthesis is described in Section 4.2.3.4.2. 

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. 

The synthesis of pyrylium salts, discovered in a classical study by Dilthey (20JPR(l0l)l77>, involves the facile acid-catalyzed cyclization of a 1,5-dicarbonyl compound. The value of this route stems from the different structural features which are acceptable in the five-carbon unit and from the variety of methods available for their synthesis. The reaction is the reverse of the synthetically useful ring opening of pyrylium salts by nucleophiles. 

In view of the development of the synthesis of various aromatic and heterocyclic compounds from pyrylium salts (80T679), the preparation of the unsubstituted pyrylium salt from pyridine is noteworthy (Scheme 269) (53CB1327). The pyridine-sulfur trioxide complex undergoes ring opening to the sodium salt of pent-2-ene-1,5-dial. This salt cyclizes in perchloric acid via the red oxonium salt. 

From reviewing the literature for the synthesis of 1,2-diazepines, just from the volume of the work it is apparent that the most preferred route to make 1,2-diazepines, starting from fragments, has been the type bg approach by using a 1,5-dielectrophile with hydrazine (a 1,2-nucleophile). In the case of ring transformation approach to 1,2-diazepines, the conversion of a pyrylium or a thiapyrylium salt to 1,2-diazepines has been the preferred route. In the end, the preferred method would depend on the nature of substituents and the unsaturation required on the 1,2-diazepine ring. 

Interest in the use of pyrylium salts in synthesis continues. 2-Methylpyridinium salts are converted into the 2-arylpyridinium compound on reaction with 2,4,6-triarylpyrylium salts in the presence of base. The methylpyridinium salt is deprotonated to the anhydrobase which behaves as an enamine, attacking the pyrylium salt at C-2, promoting a ring opening - ring closure sequence which culminates in the effective arylation of the pyridinium salt. 

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