Pyrylium salts ketones

Since 1,5-enediones are usually obtained via pyrylium salts, syntheses of the type found in Section B, 2, a have a rather theroetical interest, save for a few special syntheses. There exist several direct syntheses of l,5-enediones, e.g., from j8-chlorovinyl ketones and j8-diketones or j8-keto esters special pathways to 1,5-enediones have also been described, namely, oxidation with lead tetraacetate or with periodic acid of cyclopentene-l,2-diols. ... 

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). 

Krivun, Shian, and Dorofeenko condensed acetylacetone or dibenzoylmethane with various ketones (acetone, acetophenone, acetothienone, 1-acetylnaphthalene, or 5-acetylacetaphthene) and obtained pyrylium salts in 10-20% yield in the presence of perchloric acid. 

Presumably, jS-chloro ketones could also react similarly with methyl(ene) ketones. Another logical extension is the possibility of synthesizing pyrylium salts by dehydrogenative condensation of -chlorovinyl ketones with oleflns like styrene, in the presence of stannic chloride (the olefins so far tested, like isobutene, are not suitable structurally). 

Besides acetophenone, this reaction was also applied to p-chloro- andp-methoxyacetophenone, and even to an aliphatic ketone, acetone (although the yield was stated to be only half as large as that obtained from mesityl oxide, i.e., less than 30%, Dorofeenko and co-workers reported a 45% yield of 2,4,6-trimethylpyrylium perchlorate from acetone, acetic anhydride, and perchloric acid), and is the standard method for preparing pyrylium salts with identical substituents in positions 2 and 4. The acylating agent may be an anhydride in the presence of anhydrous or hydrated ferric chloride, or of boron fluoride, or the acid chloride with ferric chloride.Schneider and co-workers ... 

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. 

Suggest a synthetic route to the tricyclic pyrylium salt 4.6 from 2-formylcyclohexanone and perchloric acid plus a simple ketone. 

With hydroxylamine, the pyrylium salt (86) undergoes ring opening to an intermediate 1,5-enedione oxime (87) conjugate addition of the a,(3-unsaturated ketone gives (88), which in the presence of acid forms the isoxazole (89). 

It has been found (72BSF707) that in general the reaction of methylmagnesium iodide with 2,4,6-trisubstituted pyrylium salts leads to 2//-pyrans. However, as the bulk of the 2-and 6-substituents increases, minor amounts of 4//-pyrans are formed. When the pyrylium salt is unsubstituted at C-4, significant quantities of the 4//-pyran are produced, along with the corresponding 2//-pyran and unsaturated ketones. It appears that substituents in the 3- and 5-positions of the pyrylium salts have little effect on the course of the reaction. 

The acylation of unsaturated ketones constitutes one of the earliest routes to pyrylium salts (19CB1195). The reaction is better achieved with acyl halides than by anhydrides, and aliphatic are preferable to aromatic acid derivatives. The presence of a Lewis or Bronsted acid is usually necessary and iron(III) chloride, aluminum chloride, boron trifluoride and perchloric acid have found frequent application. It is considered that these interact with the acid derivative to generate the actual acylating agent. 

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). 

The reaction between acetophenone and acetic anhydride alone yields 2-methyl-4,6-diphenylpyrylium (23CB1012). It seems possible that a 1,3-diketone is formed by the acetylation of acetophenone (540R(8)59), which subsequently reacts with unchanged ketone. Alternatively, an intermediate enone derived from the condensation of two moles of acetophenone (53JA626) may be acylated to the pyrylium salt. There is supporting evidence for both reaction schemes and it is not possible to discard either alternative (Scheme 255). 

Chlorovinyl ketones are potential 1,3-diketones and provide a useful extension to the above method. In the presence of Friedel-Crafts catalysts they react with ketones to give pyrylium salts which are unsubstituted in the 4-position. The example shown in Scheme 257 illustrates the synthesis of a more complex pyrylium salt (63ZC266). 

Enamines are also potential ketones and accordingly have been used as the ketonic component in this type of pyrylium synthesis (63AG(E)394). The initial adducts, which form pyrylium salts on treatment with perchloric acid, are similar to those derived from secondary amines and pyrylium salts. The significant feature of this variant is that it gives access to pyrylium compounds which are unsubstituted at the 4- and 6-positions but which carry substituents at C-2 and C-5. More conventional enamines, such as 1-piperidinocyclohexene, afford bicyclic pyrylium salts (652), whilst polycyclic salts (653) result if cyclic chlorovinyl ketones are used. 

The chlorovinyl immonium salts (654), obtained through Vilsmeier formylation of methyl ketones, behave as 1,3-dicarbonyl compounds. In the presence of strong base they react with methyl ketones to form dienones (655). On treatment with a mixture of perchloric and acetic acids the pyrylium salt results (Scheme 259) (71JPR1110). In a similar reaction 2-naphthol is converted into the naphtho[2,1 -b]pyrylium salt (656) (79S241). 

Mechanistically, the reaction proceeds through Michael addition of the aryl methyl ketone to the enone. Hydride abstraction and cyclization then yield the pyrylium salt. The route is capable of considerable diversification and therefore has much potential. The detailed method for the synthesis of 2,4,6-triphenylpyrylium perchlorate is worthy of mention... 

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). 

The use of formaldehyde results in a pyrylium salt unsubstituted at C-4 (66BSF2959), whilst a neat variation in the ketone component enabled some 4-aryl-2,6-diethoxycarbonyl-pyrylium salts to be synthesized (81S959). 

Cyclopentenones can also be used for condensation, with o-substituted aldehydes or ketones (110) serving as reaction partners (Scheme 13). In this way thialenes 41 and 45, which have sulfur directly bonded to an aromatic ring, can be produced in one step by base-catalyzed condensation from o-mercaptobenzaldehyde and from a,/ -unsaturated cyclopentenones.110,131 Under the same conditions salicylic aldehyde gives only open-chained products fill).5,72,73 99,1 >6,1 27,128 finerai acids are required for further condensation. Thereby, pyrylium salts (90 Y = CH, X = O) are produced, from which oxalenes are formed by deprotonation (see Section I1I,A,1). 

Resonance, similar to that in pyrylium salts, was shown594,595 to exist between oxonium ion (299a) and carbenium ion (299b) forms in alkylated ketones, esters, and lactones that were obtained via alkylation with trimethyl- or triethyloxonium tetra-fluoroborates596 [Eq. (3.78)]. Ramsey and Taft597 used H NMR spectroscopy to investigate the nature of a series of secondary and tertiary carboxonium ions (300-302). 

Usually, the a-pyranic addition products (3) cannot be isolated because they isomerize immediately in a thermally allowed electrocyclic process affording acyclic dienones (4), which in many cases react further. Therefore, pyrylium salts 2A react with most nucleophiles as if they had the electronic structure 2B, and thus the pyrylium cation behaves as a useful synthon, namely the last vinylog in the series of acyl halides (Cj synthon) - p-halovinyl ketones (C3 synthon) - pyrylium (C5 synthon) [50, 51],... 

For the preparation of spirobi(pyrans), the pyrylium salt (preferably the easily purified perchlorate or fluoroborate) may be used, but it is often more convenient to merely condense the appropriate hydroxyaldehyde(s) with the requisite aliphatic ketone either directly using gaseous HC1 in ethanol, or via a base-catalyzed condensation to first give a 2-hydroxychalcone intermediate.5... 

It should be noted that the alkyl aryl ketones 191 react with the mixture of perchloric acid and acetic anhydride under the same conditions (room temperature, 10-20 h) to give the unsymmetrical pyrylium salts 197114,115. As shown in Reference 112 this reaction is also an example of electrophilic catalysis by acylium ions, proceeding via the cationic intermediates 195 and 196 (equation 62). 

The pyrylium salts can be easily ring-opened by hydrolysis to yield 1,5-pentene-diones158. Consequently, 4-acylaminopyrylium salts 396 and 397 can be precursors to enamides 395. It should be expected that / -acylaminovinyl ketones (e.g. 207 and 278) obtained by other methods (e.g. by N-acylation of enaminones159,160) can be converted into 3-azapyrylium salts116 and, by the reaction described above, they can undergo the functionalization together with lengthening of the linear carbon chain. 

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