Pyridines from pyrylium salts

Example Identification of significant experimental variables to control the product distribution in the synthesis of substituted pyridines from pyrylium salts... 

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. 

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. 

Pyridine N-oxides from pyrylium salts via cyano-ci/ -dienones and their oximes... 

Finally, a novel synthetic route involves formation of the pyridine ring from a fused pyran intermediate, e.g. (139) - (140) (70CB1250, 80JOC1918, 73JCS(P1)823). If a pyrylium salt is used, a quaternary pyridopyrimidinium salt such as (141) is formed 77KGS14S4). 

H-l-Benzopyran-4-ones — see Chromones 4H-l-Benzopyran-4-ones, 2-phenyl — see Flavones Benzopyranopyrazoles synthesis, S, 317, 341 Benzopyrano[4,3-c]pytazol-4-one synthesis, 3, 712 Benzopyrano[4,3-6]pyridine synthesis, 3, 712 Benzopyrano[4,3-ii]pyrimidine synthesis, 3, 712 Benzopyrans nomenclature, 1, 23 pyrylium salt synthesis from, 3, 873 reactions... 

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-... 

The normal pattern of coupling constants for aromatic six-membered rings is found in the heterocyclic aza systems, except that the ortho coupling to a proton a to a heterocyclic nitrogen is reduced from 7-8 Hz to 4.5-6 Hz. The J23 of pyrylium salts is still lower (ca. 3.5 Hz), but in pyridinium salts and pyridine iV-oxide it is of intermediate value (ca. 6.5 Hz) (see Table 7). 

Thieno[3,4-c]pyridines have also been prepared in an acylation-cyclization reaction from 2,5-disubstituted 3-acetonylthiophenes on treatment with acetic anhydride and perchloric acid via the thieno[3,4-c]pyrylium salts as intermediates (c/. Scheme 66) (72MIP31700, 75CHE551). 

Reaction of hydroxylamine with tri- and tetrasubstituted pyrylium salts yields pyridine iV-oxides and/or 2-isoxazo-lines via the intermediacy of keto-ketoximes <1998T9747>. The regiochemistry of 2-isoxazoline formation from unsymmetrical pyryliums, and the Beckman rearrangement of the intermediate keto ketoximes have also been explored C1998T9747, 1999T15011>. 

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