Pyridines from pyryliums

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

Phosphorus. Substituted phosphorus analogues of pyridine (phosphinines, A3-phosphabenzenes, also called phosphonins or phosphorins) were first prepared by Markl starting from pyrylium cations their chemical properties suggest that their aromaticity is lower than that of pyridine (e.g. phosphinine 186, Scheme 72).230-232 Molecular calculations for other six-membered jr-systems with planar tricoordinate phosphorus, such as phospininines 186 and 187, have evidenced their aromaticity (Scheme 72).156... 

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. 

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. 

Synthesis from Pyrylium and Nitrllium Salts. Russian workers31,59 have found that acetonylthiophenes yield pyrylium salts when allowed to react with anhydrides in the presence of 70% perchloric acid, and that these salts are converted into thienopyridines by treatment with ethanolic ammonia. For example 4-acetonyl-2-methylthiophene and acetic anhydride gave 2,5,7-trimethylthieno[2,3-c)pyrylium perchlorate (33), from which 2,5,7-trimethylthieno[2,3-c]pyridine (34) was obtained. 

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... 

Nitropyrido[l,2-A]quinolin-6-ium-l 1-olate (6%) was isolated from a reaction mixture obtained by photoirradiation of crystalline photochromic 2-(2, 4 -dinitrobenzyl)pyridine for 10 days <2004JP0865>. Reaction of l-(3-chloropropyl)-6,7-dimethoxy-3-methylbenzo[c]pyrylium perchlorate with hydrazines and hydroxylamine in refluxing MeOH afforded 9,10-dimethoxy-6-methyl-, -4,6-dimethyl-l,2,3,4-tetrahydropyridazino[6,l-tf]isoquinoli-nium, and 9,10-dimethoxy-6-methyl-l,2,3,4-tetrahydro[l,2]oxazino[3,2- ]isoquinolinium, perchlorates, respectively <2004CHE1131>. 

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). 

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