Synthesis of Pyryliums

Pyrylium rings are assembled by the cyclisation of a 1,5-dicarbonyl precursor, separately synthesised or generated in situ. 

5-Dicarbonyl compounds can be cyclised, with dehydration and in the presence of an oxidising agent. 

Mono-enolisation of a 1,5-diketone, then the formation of a cyclic hemiacetal, and its dehydration, produces dienol ethers (4//-4-pyrans) which require only hydride abstraction to arrive at the pyrylium oxidation level. The diketones are often prepared in situ by the reaction of an aldehyde with two mols of a ketone (compare Hantzsch synthesis, section 5.15.1.2) or of a ketone with a previously prepared conjugated ketone - a chalcone in the case of aromatic ketones/aldehydes. It is the excess chalcone which serves as the hydride acceptor in this approach. 

Early work utilised acetic anhydride as solvent with the incorporation of an oxidising agent (hydride acceptor), often iron(III) chloride (though it is believed that it is the acylium cation which is the hydride acceptor) latterly the incorporation of 

3-dichloro-5,6-dicyano-l,4-benzoquinone, 2,6-dimethylpyrylium or most often, the triphenylmethyl cation have proved efficient. In some cases the 4i/-pyran is isolated then oxidised in a separate step. 

6-Dimethyl-4-pyrone condenses with aromatic aldehydes at a methyl and can be lithiated and thereby substituted.  

4-Dioxygenated pyrones exist as the 4-hydroxy tautomers. Such molecules are easily substituted by electrophiles, at the position between the two oxygens (C-3) and can still be side-chain deprotonated.  

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Under the influence of acids, cw-2-ene-l,5-diones (20) or their enol forms (19) are converted by dehydration back into pyrylium salts. Accordingly, any synthetic method resulting in 1,5-enediones is, in fact, a method for the synthesis of pyrylium salts. 

A general method for the synthesis of pyrylium salts is the cyclodehydration of 1,5-dicarbonylalkanes (Scheme 4.4). Acetic anhydride is commonly used as both solvent and reagent, but since the initial product is a 4/f-pyran, an oxidant such as the triphenylmethyl (trityl) cation in the form of triphenylmethyl hexachloroantimonate is added (Ph3C + [H ] -> Ph3CH). In certain cases, however, it is advantageous to isolate the pyran and to oxidize it in a separate step. 

The synthesis of pyrylium salts, discovered in a classical study by Dilthey (20JPR(l0l)l77>, involves the facile acid-catalyzed cyclization of a 1,5-dicarbonyl compound. The value of this route stems from the different structural features which are acceptable in the five-carbon unit and from the variety of methods available for their synthesis. The reaction is the reverse of the synthetically useful ring opening of pyrylium salts by nucleophiles. 

Again, the extension of this route to the synthesis of pyrylium salts with fused alicyclic moieties has been reported involving the use of cycloalkanones as the ketonic component (67T1565). 

Russian workers have advocated the use of orthoformates in the synthesis of pyrylium salts and their benzologues. In the presence of acids, alkyl orthoformates are converted into dialkoxycarbocations, which are efficient C-acylating agents. Even in the absence of a Friedel-Crafts catalyst and under mild conditions, acetophenone is converted into the pent-2-ene-l,5-dione (648), which cyclizes to the 2,6-diphenylpyrylium salt (Scheme 254) (71CHE147). Yields decrease with increasing alkyl chain length in the orthoformate. There is evidence that a 3-alkoxymethylpyrylium salt is the initial product. 

This approach to pyrylium salts has much to offer and it has been extended to variously substituted acetophenones (65JOC1684) and even to acetone, though in only fair yield. It remains a valuable method for the synthesis of pyrylium salts with identical substituents at C-2 and C-4. 

Some of the earliest examples of the synthesis of pyrylium salts require an oxidation stage. In 1896, Kostanecki and Rossbach noted the fluorescence, now known to be caused by 2,4,6-triphenylpyrylium, produced when l,3,5-triphenylpentane-l,5-dione was heated with concentrated sulfuric acid. It was later found that acetic anhydride and iron(III) chloride was a more efficient reagent than sulfuric acid (17JPR(95)107). 

Although the value of this route has been improved by developments in the synthesis of 1,5-diketones, it is often easier to generate the diketone in situ. Provided that the reaction is carried out in the presence of a hydride acceptor, a direct synthesis of pyrylium salts is available from simple precursors. 

Cyclic ketones react with unsaturated ketones to form fused pyrylium salts (667) (58JCS1978), whilst the use of phenylacetaldehyde allows the synthesis of pyrylium salts unsubstituted at C-6 to be achieved (65BSF1944). 

Alexandru T. Balaban was born in Timigoara, Romania in 1931 and studied mathematics, chemistry, and radiochemistry in Bucharest. He obtained a PhD in organic chemistry under the guidance of Costin D. Nenitzescu in 1959, shortly after discovering a novel synthesis of pyrylium salts and the birth of his son Silviu. He was head of the Laboratory for Labeled Organic Compounds at the Institute of Atomic Physics in Bucharest between 1961 and 1975 and during... 

Synthesis of pyrylium salts by acylation of unsaturated ketones or by diacylation of alkenes. 

PjT ones and 2-p5Tones have been the first starting materials for the synthesis of pyrylium salts. The preparation of 2,6-dimethyl-4ZI-pyran-4-one (8) from dehydroacetic acid and boiling hydrochloric acid has been extensively investigated. " Other available... 

The retrosynthesis of pyrylium ions (Fig. 6.2) is based on the ring-opening reaction by hydroxide ions (see p 224) and leads to 1,5-dicarbonyl compounds 20-22. From these starting materials the synthesis of pyrylium ions can occur by cyclocondensation, their oxidation level is brought about by removal of a hydride ion or of a suitable leaving group ... 

If an unsaturated dicarbonyl precursor is available then no oxidant needs to be added a synthesis of pyrylium perchlorate itself falls into this category -careful acid treatment of either glutaconaldehyde, or of its sodium salt, produces the parent salt (CAUTION explosive). " ... 

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