Pyrylium salts formation

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). 

In the hands of Collie and Tickle in 1899 this reaction gave the first crystalline pyrylium salts. The salt character of the compounds was proved by conductivity measurements the basicity of 2,6-dimethylpyrone was found to be a little higher than that of urea. Basicities of other pyrones decrease in the order 2,6-dimethyl-> 2-phenyl-6-methyl-> 2,6-diphenylpyrone, paralleling the dipole moments. These hydroxypyrylium salts hydrolyze in water to pyrones. " The formation of salts of 2,6-dimethylpyrone with organic acids was investigated by Kendall,and with mineral acids by Cook. 11 ... 

The cyclization of 1,3,5-triketones to pyrones will not be discussed here, although this is a related reaction, because pyrones are not true pyrylium salts. Mention will be made, however, of the formation of 2,6-diphenyl-4-pyrone from 1,3-dibenzoylallene this ketone adds secondary amines leading to 3-dialkylamino-l,5-diphenyl-4-penten-l,5-diones, which arc cyclized by hydrogen chloride in acetic acid to 2,6-diphenyl-4-dialkylaminopyrylium chlorides (R = Me and/or Ph) (see Scheme. 5). 

Tetramethylethylene behaves in the AlCIs-catalyzed diacetylation as 155 (Aik = iso-Pr)affording2,6-dimethyl-4-isopropylpyrylium. Although the olefin acylation had been investigated by many chemists beginning with Kondakov (cf. Nenitzescu and Balaban and Balaban and Nenitzescu ), the formation of pyrylium salts had escaped notice because they are water-soluble and had been discarded after hydrolysis of the reaction mixture. Only in the study of the ZnCla-catalyzed acetylation of diisobutene had a crystalline product been observed by Byrns and Doumani its reaction... 

Quinolizinium and other fused pyridinium salts are formed when a-methylheterocycles react with 2,4,6-triphenylpyrylium, which thus behaves as a C3-synthon <96MC99>. Pyrylium salts also feature in a stereocontroUed route to conjugated dienynes which has led to a synthesis of Carduusyne A, a marine metabolic fatty acid <96TL1913> and in the formation of pyridinium containing crown ethers <96LA9S9>. 

On treating diisobutene with acetic anhydride and anhydrous zinc chloride, A. C. Byrns and T. F. Doumani had isolated in 1943 a crystalline compound to which they had ascribed the structure of a zinc complex with a 1,3-diketone 40 the correct pyrylium chlorozincate structure was established by A. T. Balaban et al.41 in 1961, after extended investigation on the formation of pyrylium salts by alkene diacylation.42 This formation again had remained undetected for many decades during which alkenes had been acylated but only the water-insoluble monoacylation products had been investigated, whereas the water-soluble pyrylium salts went into the sink with the Lewis or Bronsted acid catalysts that had been used in the acylation. 

The interaction of 2,6-diphenyl-4-pyrone with carbazole and phosphorus oxychloride led interestingly to the pyrylium salt 48. The formation of 9-phenylcarbazole by addition of carbazol-9-yllithium to benzyne has been recorded. ... 

The reactions in Methods A, B and C, which all start from pyrylium salts are analogous to the well-known conversions of 2.4.6-substituted pyrylium salts 27 with ammonia, primary amines, hydrogen sulfide or the anions of CH activated compounds to the corresponding heterocyclic or isocyclic aromatic systems The first step involves addition of the basic phosphine at C-2 (or C-6) to form 2S. Ring-opening, ring-closure and elimination of water are likely steps in the formation of the product 2. 

The cited160,161 formation of polychloropyrans 120 -> 121 and 120 - 122 may be regarded as proceeding via 2-phenyl-3,4,5-trichloro- or 3,4,5-tri-chloropyrylium chlorides, which are attacked by a chloride ion. The transformation of pyrylium salts 219 to 4-formyl-4//-pyrans 220 with hippuric acid, acetic anhydride, and sodium acetate2651 is discussed in Section IV,J. 

In contrast to 4//-pyrans, the 2//-pyrans have been rarely reported to be aromatized to pyrylium salts. 2,6-Dimethyl-4-methoxy-2//-pyran (323) was easily converted to the corresponding perchlorate 373 with perchloric acid.318,319 A similar oxidation was reported for 2,4,6-triphenyl-2//-pyran.217 The formation of pyrylium salts 375 and 377 from 374 and hydrogen chloride261 or from 376 and perchloric acid181 are not oxidations. 

A ring transformation similar to the oxidative conversion of the pyrylium salts to the acylfurans is the formation of 5-alkyl-3,4-dichlorofuran-2-carbonyl chlorides from tetra-chloro-2//-pyrans by oxygen at room temperature. A hyperoxide is proposed as an inter-... 

Pyrylium salts, especially the 2,4,6-triaryl substituted, react with a wide variety of nucleophiles some of which lead to the formation of rings other than benzene or pyridine. Sodium sulphide, for instance, attacks the pyrylium ring at C-2 to produce the blue-coloured dienone (78) which then cyclizes on treatment with add to the thiopyrylium salt (79) (56HCA207). 

The formation of furans from pyrylium salts under oxidative conditions has been mentioned in Section 2.23.2.2. Ring opening and recyclization of 4-chloromethyl-2,6-dimethyI-pyrylium perchlorate (83) by aqueous alkali and DMF leads to 2-methylfuran-4-ylacetone (84) (77CHE918). When 2,3,4,5-tetraphenylpyrylium perbromide is hydrolyzed to the dienone and then subjected to bromination-dehydrobromination, 2-benzoyl-3,4,5-triphenylfuran (85) is formed. 

Methylene groups of pyrylium cations also react under mild conditions with nitrosoben-zenes in the presence of acetic anhydride and an alkali metal salt, which plays an essential role in the formation of Schiff s bases (116). The latter are hydrolyzed to the carbonyl compound (117) (71BSF3603). It is possible to form potential dyes by treatment of pyrylium salts with ortho esters such as triethyl orthoformate. The reactants are heated together in acetic anhydride or pyridine and trimethine dyes of type (118) and (119) are formed (70JHC1395, 71JOC600, 59CB2309). 

Ammonia and amines open pyran-2-one rings and the acyclic products may cyclize again on acidification to pyridones or a benzene ring, a reaction reminiscent of those of pyrylium salts (Section 2.23.2.3). Under mild conditions, unsaturated amino acids such as (275) are formed but at higher temperatures and longer reaction times, a pyridone (276) or benzamide (277) is formed. The probable course of benzamide formation is as shown in Scheme 14 (74JOU852). 

Further details of the formation of chromenes from pyrylium salts can be found in Chapter 2.23. 

An attempt to prepare 2-(2-nitrophenyl)-4,6-diphenylpyrylium from l,3-diphenylprop-2-en-1 -one and 2-nitroacetophenone gave only 2,4,6-triphenylpyrylium (58BSF1458). Similarly, substantial formation of this symmetrical pyrylium salt was observed during syntheses of unsymmetrically substituted salts. Thus, pinacolone and chalcone afforded both 2-f-butyl-4,6-diphenylpyrylium and the 2,4,6-triphenyl derivative. The latter product is considered to arise from a retro-aldol reaction of the enone into a mixture of benzaldehyde and acetophenone the latter reacts with unchanged chalcone to give the unrequired salt (80T679). 

The formation of a mixture of pyrylium salts when 2-acetylpyridine and chalcone reacted in perchloric acid was overcome by treating the reactants with ethanolic sodium hydroxide. The pentanedione was isolated and subsequently oxidized by reaction with chalcone and boron trifluoride (82JCS(P1)125). 

The problem of separation of two pyrylium salts can be circumvented by careful selection of the reactants. In the two examples quoted above, the use of acetophenone with the appropriately substituted chalcone (668 R = 0-O2NC6H4 or Bu ) results in formation of... 

The use of ethyl acetoacetate in this route allows the formation of a 3-ethoxycarbonyl-pyrylium salt (68JOC1102). Some care is appropriate in this type of reaction in the absence of an added hydride acceptor, however, since the chalcone may undergo a Michael condensation with the intermediate 1,5-dione, leading to side products. 

Additional supporting evidence for the mechanism includes the formation of pyrylium salts when arylacetyl chlorides, which yield ketenes by loss of HC1, react with the phosphorane (63CR(257)926). It is also known that diphenylketene reacts in a similar manner to give a pyran, whilst aryl isocyanates yield pyran-4-one derivatives. 

The variable valency of sulfur allows the formation of S-oxides (11) which unlike thiabenzene 1-oxides are non-aromatic and exist in half-boat conformations (78CC197). On the other hand, acid treatment of 6-hydroxy-6H- 1,2-oxazines (12) yields cations (13) which are analogous to pyrylium salts (74ZOR1513). 

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