2.3.6- Trisubstituted pyrylium salts

A convenient method leading to pyrans (38) consists in the nucleophilic addition of R anions to 2,6-disubstituted pyrjdium salts, in which the y-position (secondary carbonium ion) is more reactive than the a-positions (tertiary carbonium ions), in opposition to the reactivity of 2,4,6-trisubstituted pyrylium salts.Krohnke and Dickore as well as Dimroth and WolH showed that 2,6-diphenyl-pyrylium salts add the anions R of nitromethane, 1,3-diketones, malonodinitrile, ethyl cyanoacetate, and benzoylacetonitrile. Similar reactions are known in the flavylium series. -Nonactivated R ... 

Any change of individual substituents in 2,4,6-trisubstituted pyrylium salts results, as a rule, in negligible effects in comparison with the variations produced by the organometallic agents. 

Further examples of preparative aromatization of 4//-pyrans are the syntheses of 2,4,6-trisubstituted pyrylium salts 172c- 388,242 389->390,251 391a - 392a,222 358 391b - 392b,2638 and 391c - 392c.264... 

Hydrogen peroxide reacts with 2,4,6-trisubstituted pyrylium salts to cause ring contraction (213 — 214). If there is a free a- or y-position, pyrylium salts can be oxidized to pyrones (215 — 216). 

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). 

There have been few mass spectral studies of pyrylium salts, possibly as a result of their low volatility. The examples reported so far have been concerned with the behaviour of alkyl- and aryl-substituted compounds under electron impact conditions. Information regarding the parent compound appears to be lacking. In the initial work, use was made of 2,4,6-trisubstituted pyrylium salts. The halides (iodides and bromides) were examined because of their enhanced volatility over the corresponding perchlorates and tetrafluorobo-rates <7lOMS(5)87>. 

The distribution of charge in the resonance forms (28)-(31) suggests that nucleophiles may attack at C-2, C-4 or C-6 (or at C-2 or C-4 in 1-benzopyrylium cations, and at C-l, C-3 or C-4a in 2-benzopyrylium ions) but they most commonly add at C-2 for example, attack by cyanide ion gives a 2//-pyran (37) which exists partly or wholly as the acyclic isomer (38). Steric and electronic effects in the reactants probably have a role in determining the course of the reaction of trisubstituted pyrylium salts with nucleophiles. A mixture of both 2H- and 4H-pyrans is sometimes produced, for example, from methoxide ion and 2,4,6-triphenylpyrylium perchlorate (39) no acyclic product was detected in this reaction... 

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. 

It is usual to produce 2,4,6-trisubstituted pyrylium salts by this method, otherwise isolation of the products is difficult. Although yields are only fair, considerable variation in the substituents is possible and some satisfactory examples are known. The detailed preparation of 2,4,6-trimethylpyrylium perchlorate also includes a brief survey of methods and merits of the procedure (73OSC(5)ll06). 

Pyryliiim [181-183] and isobenzopyrylium [184] salts have been shown to be polaro-graphically reducible in a one-electron reduction. In cyclic voltammetry in aprotic solvents, 2,4,6-trisubstituted pyrylium salts show two peaks the shape of the peak depends on the rate of dimerization. This process occurs more rapidly at C-4 than at C-2 (C-6) [182, 183], and the dimerization takes place spontaneously for 4-unsubstituted pyrylium salts. The equilibrium between radicals and dimer is displaced in favor of the radicals on introduction of electron-withdrawing substituents such groups enhance the aromatic character of the radical [185]. If the reduction of pyrylium salts is made in the presence of an alkyl iodide a fair yield of the 4-alkylated 4i/-pyrane is isolated with the dimer [182]. 

JV-Alkyl- and A-aryl-pyridinium salts are obtained analogously from 2,4,6-trisubstituted pyrylium salts and primary aliphatic or aromatic amines, generally in excellent yields.1028... 

Dicarbonyl compounds and aryl methyl ketones condense in acetic anhydride in the presence of strong acids to give 2,4,6-trisubstituted pyrylium salts 24 ... 

When reacted with aryl methyl ketones in acetic anhydride in the presence of a hydride acceptor, e.g. FeCl3, chalcones 32 yield trisubstituted pyrylium salts 34 Dilthey synthesis) ... 

Trisubstituted pyrylium salts yield 2,4,6-trisubstituted phosphabenzenes 16 (MArkl 1966) when treated with phosphanes such as tris(hydroxymethyl)phosphane, tris(trimethylsilyl)phosphane or phosphonium iodide (according to the reaction principle on p 225) ... 

It will be observed that most syntheses yield pyrylium salts in which positions 2,4, and 6 are substituted. Since according to formulas Ib-lc these positions have a partial positive charge, it can readily be understood why electron-donating substituents (hydroxy, alkoxy, alkyl, or aryl) in these positions stabilize the pyrylium salts. Only three pyrylium salts which do not have substituents in either a-position have been reported and few unsubstituted in y or in one a-position they are less stable toward hydrolysis, and in the case of perchlorates they explode more easily, than 2,4,6-trisubstituted compounds. In fact, the former are secondary, the latter tertiary carbonium ions. This fact also explains why the parent compound (1) was prepared only in 1953. 

A 2,4)6-trisubstituted 2H or 4/f) pyran (38, R = R = Ph) was reported to result in low yield by catalytic reduction of 2,4,6-triphenyl-pyrylium salts by oxidation or by treatment with concentrated sulfuric acid it regenerated the triphenylpyrylium cation. There was no subsequent confirmation of this reaction. The reduction of pyrylium salts with sodium borohydride affords 1,5-diones by way of 4H-pyrans and 2,4-dien-l-ones by way of 2H-pyrans. ... 

Alk = Et), a-methylstyrene (156, Ar = Ph), and allyl-benzene (160, Ar = Ph) are representatives of the four types of monosubstituted propenes (olefins 157 and 158, etc. written in Table I as equilibrium pairs undergo equilibration during the course of the reaction and yield the same pyrylium salt on diacylation). Disubstituted propenes which gave pyrylium salts on diacylation are 2-pentene (163, Alk = Me) and 1,2-diphenylpropene (164, Ar = ph),305 3-ethyl-2-pentene represents a trisubstituted propene... 

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. 

Figure 14 Reactions of pyrylium salts (usually 2,4,6-trisubstituted).

On the other hand, 1,1,1-trisubstituted alkanes behave similarly to aldehydes, yielding pyrylium salts (128) with identical substituents in positions 2 and 6. Thus, Dorofeenko and co-workers condensed 2 moles of acetophenone with 1 mole of benzotrichloride in the presence of perchloric acid obtaining 2,4,6-triphenylpyrylium perchlorate402 with 1 mole of ethyl orthoformate, they obtained 2,6-diphenyl-pyrylium perchlorate (57) 406 from o-hydroxyacetophenone, ortho-formic ester and perchloric acid, 4-ethoxybenzopyrylium perchlorate was formed.406a... 

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