Pyrylium salts pyridines

Substituents in 2.4.6-positions Benzene Pyridine Pyrylium Salt X -Phosphorin... 

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... 

Direct conversion of pyridines into pyrylium salts is not possible (the reverse reaction is, however, very easy). However, Klages and Trager succeeded in performing the first synthesis of the parent compound 1 by the following reaction sequence, which was recently repeated with the pentadeutero derivative. 

Dilthey wished to adapt, for pyrylium, syntheses which with ammonia were known to yield pyridines. Indeed, there is a marked similarity, and probably a common mechanism between certain syntheses of pyrylium salts and of p5rridines, e g., Chichihabin s and... 

Olefin diacylation with carbonjd-labelled acid derivatives is ai excellent method for obtaining O-labeled pyrylium salts (194) and hence, ring-labeled aromatic compounds such as pyridines ana phenols. 

Method B involves the preparation of precursor of 2-alkyl-l-benzo-pyrylium salts, as shown in Scheme ll.50 2-Alkylbenzopyrylium salts have been prepared by condensation of salicylaldehyde with appropriate ketone in acetic acid or by alkylation or reduction of coumarin or chromone derivatives. Reaction of 2-alkylbenzopyrylium salts with salicylaldehyde gives directly a spirodibenzopyran or 2-vinynologue benzopyrylium salt 17 which then can be converted into the spirodibenzopyran by piperidine or pyridine. 

Three different fused systems have been reported in the literature thieno[3, 2 4,5]thieno[2,3-c]pyridine (f/r-thiophenes), thieno[2, 3 4,5]thieno[2,3-c]pyridine (tram- thiophenes) and thicno[3,2-g]thicno [3,2-d pyridine derivatives. So far, the parent thienothienopyridines have only been prepared via the corresponding pyrylium salts (see below) all others are benzo or extended carbocyclic derivatives, for example, thienothienoquinolines. 

Trimethylpyrylium perchlorate is a very versatile and useful starting material. Thus its reaction with cyclopentadienyl-sodium has made 4,6,8-trimethylazulene 12 easily available for general studies of the properties of azulenes 18 and for the synthesis of related compounds.14 In addition, pyrylium salts are readily converted to a variety of pyridine derivatives 9 15 as well as to derivatives of nitrobenzene16 and phenol.9 17,18 It is clear that its value as a starting material is such that it is receiving wide use. 

Triphenylpyrylium tetrafluoroborate is a versatile and useful stable starting material. Its reaction with nitromethane under basic conditions has made 2,4,6-triphenylnitrobenzene easily available. In addition, pyrylium salts are readily converted to a variety of pyridine derivatives i i . 20 including alkyl- and arylpyridinium salts, to thiopyrylium salts," and to substituted azulenes. ... 

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 other major group of oxygen heterocycles which can give pyridines are the pyrylium salts. With ammonia or ammonium salts the products are pyridines, while with primary amines the products are pyridinium salts, as shown in equation (91). The simplified mechanism shows the important stages it is notable that a second molar equivalent of base (which... 

However, radical intermediates cannot be definitely excluded, at least not in the reaction of pyiylium salts in pyridine. Steuber showed that such pyrylium salts as 2.4.6-triphenyl-pyrylium-or 2.4.6-tri-tert-butyl-pyrylium-tetrafluoroborate can be reduced to stable pyryl radicals 32 by pyridine this reduction proceeds particularly smoothly if traces of copper powder are added. 

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). 

However, 2,4,6-trisubstituted pyrylium salts with certain active methyl and methylene compounds undergo ring fission and subsequent cyclization to benzenoid products. 2,4,6-Triphenylpyrylium ion (261 Z = O) in this way forms 2,4,6-triphenylnitrobenzene (299) with nitromethane and the substituted benzoic acid (300) with malonic acid, the latter reaction involving a decarboxylation. In reactions of this type, 1,3-oxazinium salts react with active hydrogen compounds to give pyridines (Scheme 25). 

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. 

Hydrogenation to chromanes, oxidative degradation, and oxidation to pyrylium salts in acid medium have been known for a long time.3 A series of substituted benzopyrylium salts has been recently prepared by oxidation of chromenes with tritylium perchlorate.97 Oxidation of 4-phenylchromenes to coumarins with Cr03-pyridine complex or with Se02 in dioxan has been reported.186... 

A general method for the attachment of a pyridine ring to a furan nucleus consists of the reaction of appropriate pyrylium salts (e.g. 55) with ammonia (Scheme 11) (73CHE416). Pyrylium and hence pyridine derivatives of benzofuran may also be prepared in this way. 

Russian workers have reported that 3-acetonylthiophenes yield pyrylium salts when allowed to react with acid anhydrides in the presence of 70% perchloric acid. These salts are transformed into thieno[2,3-c]pyridines by treatment with ethanolic ammonia (Scheme 66 (71KGS320) compare the preparation of furo[2,3-c]pyridines). A number of variously substituted thieno-[2,3-c]- and -[3,2-c]-pyridines have been made in this way. 

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). 

Some nucleophiles open the pyrylium ring to give intermediates which are capable of spontaneous or add-induced cyclization to a new ring. The conversion of pyrylium salts into pyridines is the most thoroughly studied example and was first described in 1911 (B-64MI22300). Ammonia, ammonium acetate or carbonate react with pyrylium salts such... 

---