Pyridines and pyrylium salts

The products can be converted into pyridines and pyrylium salts, as formulated in equations (II) and (III). 

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. 

As expected on the basis of the higher stability of sulfonium salts as compared with oxonium salts, thiopyrylium cations are more stable and less reactive than pyrylium cations hydride-accepting ability decreases in the order pyrylium> selenopyrylium> thiopyrylium [95], 2,4,6-Triphenyl-thiopyrylium salts react with ammonia and primary alkylamines forming the corresponding pyridine and pyridinium salts, respectively, but they do not react with aniline or its derivatives [96-99], As described below, the Se- or Te-analogs are less stable than the thiopyrylium salts. 

Friedel-Crafts acylation of t-butanol (Scheme 6) followed by treatment with ammonia gives a mixture of 2,7-naphthyridines (379 R = Me, Et, Pr", Pr, Bu) and pyridines (380) (38-91% yield) <84BSF449>. Heterocycles (379) are the major products in these reactions and pyrylium salts have been proposed as reaction intermediates. Unsymmetrical naphthyridines (382) have been obtained as the major products of the reaction of alkenones (381) under similar conditions (Scheme 6) <84BSF454>. 

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. 

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 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). 

Pyrylium cations form pyridines with ammonia and pyridinium salts with primary amines (B-82MI 505-02). For example, 2,4,6-triphenylpyrylium cation (261 Z=0) yields 2,4,6-triphenylpyridine with ammonia, the corresponding 1-methylpyridinium salt with methylamine, and pyridine 1-arylimines with phenylhydrazine. Xanthylium ions (210), where ring opening cannot readily occur, form adducts (262) with ammonia, amines, amides, ureas, sulfonamides and imides. Similar adducts (e.g. 263) are formed by benzo[( ]pyrylium ions. 

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). 

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. 

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