Reactions of Benzopyryliums

Much more work has been done on 1-benzopyryliums than on 2-benzopyryliums, because of their relevance to the flavylium (2-phenyl-l-benzopyrylium) nucleus, which occurs widely in the anthocyanins, and much of that work has been conducted on flavylium itself. As with pyrylium salts, benzopyrylium salts usually add nucleophiles at the carbon adjacent to the oxygen. 

No simple examples are known of electrophilic or radical substitution of either heterocyclic or homocyclic rings of benzopyrylium salts flavylium and l-phenyl-2-benzopyrylium salts nitrate in the substituent benzene ring. Having said this, the cyclisation of coumarin-4-propanoic acid may represent Friedel-Crafts type intramolecular attack on the carbonyl-O-protonated form i.e. on a 2-hydroxy-1- 

Oxidative general breakdown of flavylium salts was utilised in early structural work on the natural compounds. Baeyer-Villiger oxidation is such a process whereby the two halves of the molecule can be separately examined (after ester hydrolysis of the 

Water and alcohols add readily at C-2, and sometimes at C-4, generating chromenols or chromenol ethers. It is difficult to obtain 2i/-chromenols pure since they are always in equilibrium with ring-opened chalcones.  

Controlled conditions are required for the production of simple adducts, for under more vigorous alkaline treatment, ring opening then carbon-carbon bond cleavage via a retro-aldol mechanism takes place and such processes, which are essentially the reverse of a route used for the synthesis of 1-benzopyryliums (section 9.3.1) were utilised in early structural work on anthocyanin flower pigments. 

Coumarins, chromones, and isocoumarins react with both nucleophiles and electrophiles in much the same way as do quinolones and isoquinolones. 

---

Somewhat more exotic is the reaction of benzopyrylium salts with alkenes, which yields... 

An account of domino reactions of benzopyrylium triflates with l,3-bis(silyl enol ethers) has been published <07SL1016>. 

Enohzable carbonyl compounds could also be employed in the gold(III)-catalyzed [4+2] cycloaddition with 2-alkynylbenzaldehydes to give the corresponding naphthyl ketones (Scheme 21.43) [50]. This reaction may proceed via the inverse electron demand Diels-Alder reaction of benzopyrylium intermediates with the enol form of carbonyl compounds followed by dehydration. 

The reaction of sodium azide with 2-benzopyrylium perchlorates 4 gives unstable l-azido-2-benzopyrans 5, which lose nitrogen on heating to give mixtures of 3,1-benzoxazepines 6 and anils 7.25... 

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. 

In preparing 6-alkoxy and 6,7-dialkoxy derivatives, it is convenient to react esters 12 with an acid anhydride in the presence of a Lewis acid or, preferably, perchloric acid to produce a benzopyrylium salt (14), presumably via 13 (70KGS200) (Scheme 2). Reaction of 14 with ammonia gives then the isoquinolinols 15 in high yields, where X = alkoxy, R1 = H, Me, Pr, /-Pr, and R2 = H or alkyl group (88JMC1363). 

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... 

The reaction of several amines with 7-methoxy-3-phenylbenzopyrylium perchlorate has been shown to yield the corresponding 2-substituted 3-phenylchromene (78JCS(P1)88), although the reaction of secondary amines with simple benzopyrylium salts gives mixtures of chrom-3-enes and chrom-2-enes (72JOC1069). 

Treatment of 2/Z-chromenes which have at least one hydrogen atom at C-2 with acid gives a mixture of chroman and benzopyrylium salt (68T949). Reaction of a chromerte with triphenylmethyl salts gives essentially only the benzopyrylium salt (67AC(R)1045, 72CR(C)(274)650>. 

Reactions of the hydronium ion with porous active carbon have been investigated in aqueous systems. Hydronium-ion activity, specific-anion concentration, and carbon dosage have been among the major variables studied. Rates of reaction have been found to be limited by pore diffusion, as partially verified by activation energies of —(2 to 3) kcal. per mole-deg. The results can be interpreted partly in terms of a reaction of the hydronium ion and dissolved oxygen with a surface benzpyran (chromene) group to produce hydrogen peroxide and a surface benzopyrylium (carbonium) ion with a sorbed anion, and partly in terms of physical sorption of the acid on the carbon surface. 

Benzopyrylium salts have not been found in nature, and in spite of their ability to take part in recyclization reactions, until recently it was considered that there were no specific features in their transformations relative to monocyclic pyrylium salts (79MI2), and the scope of these transformations has been considered as rather restricted (71CB2984). The reason for such a conclusion was based on the incorrect interpretation of the effects of benzoannelation on reactions of 2-benzopyrylium cations so far no review on this subject has been published. 

The reactions of 2-benzopyrylium salts can be divided into five groups ... 

Dimerization and further transformation of dimers. This reaction type has to be considered separately since it includes practically all reactions of 2-benzopyrylium salts mentioned here. 

The formation of isolable adducts in reactions of 2-benzopyrylium salts with nucleophiles depends on the structure of the nucleophile and conditions of the experiment. Thus, the stable adducts 108-113 were obtained as... 

The transformations of adducts may be conventionally classified into two types. The reactions of the first duplicate transformations of the initial 2-benzopyrylium salts and are discussed in the corresponding sections, whereas the second type is different. The latter conversions of the isolable adducts are obviously determined by the annelated benzenoid ring its... 

The ability of 5-oxoniachrysenes 67 to form stable adducts with ammonia, methyl amine, and hydrazine is not usual for 2-benzopyrylium (cf. Section III,C,2), but is often encountered for 1-benzopyrylium (chro-mylium) salts (51 Mil). At the same time, no rupture of the C6—Cring bond was observed for 2-benzo- or 1-benzopyrylium salts under the conditions used. A remote similarity to C6—Crjng bond rupture may be seen in reactions of 2-benzopyrylium salts with sodium azide (Section III,C,2) or with hydrogen peroxide (Section III,C,4,b,ii). 

Since the reactions of 2-benzopyrylium salts with nucleophiles (in accordance with the ANRORC scheme) are seldom stopped at the ringopening step (as a rule, formation of 1,5-dicarbonyl compounds takes place), it is expedient to examine at once the reactions completed by formation of a new ring. Such a process may occur with participation of both the added nucleophile and the a-alkyl substituent in the heterocyclic... 

Evidently, the stability of 3-hydroxy-3,4-dihydroisoquinolines 137, formed as the result of heterocyclization, is also determined by the anne-lated benzenoid ring. The lower tendency toward aromatization for these compounds, compared to monocyclic analogs, leads to the ability of 137 to react as a cyclic azomethine. The addition of a molecule of nucleophile to the C=N bond causes opening of the isoquinoline ring and formation of a new ring system (for instance, a-naphthols 141 in alkaline aqueous solutions). Such conversions occur even under conditions of the recyclization reaction of 2-benzopyrylium salts, namely, on heating 137 in alcoholic ammonia a mixture of isoquinoline 138 and a-naphthylamine 140 results (88MI1). 

The application of acetic acid catalysis in reaction of 2-benzopyrylium salts with primary amines4, in contrast to the reaction with ammonia, does not lead to a simple result. Thus, if in 30 R3 is not Aik, excluding the alternative formation of a-naphthylamines of type 153, the use of acetic acid catalysis leads to isoquinolinium salts 152 in high yields (89KPS75), whereas without acetic acid, diketones 166 were the only products of interaction between 2-benzopyrylium salts 30 and primary amines. 

The formation of a-naphthylamines 140 and 153 in reactions of 2-benzopyrylium salts with ammonia and primary amines is not always an undesirable process. The synthetic application of a-naphthylamines is connected with the chemistry of benzo[c]phenanthridine alkaloids 132 (78MI1 81H474). 

The only known example of a reaction of 2-benzopyrylium salts with hydroxylamine is a normal O - N exchange and formation of isoquinoline N-oxide 181 (70KGS1308). 

Similar to the reaction of 2-benzopyrylium salts with ammonia (Section III,C,4,a,i), an excess of competing nucleophiles in reactions with secondary amines is undesirable. Thus, the interactions of l-ethyl-3-methyl-substituted salt 183 with 40% aqueous solution of dimethylamine leads to a-naphthol 189 as the major product (79TH1). 

Interestingly, a-carboxy-substituted monocyclic pyrylium salts 195, probably because of a lower tendency towards nucleophilic addition in comparison with 2-benzopyrylium salts (Section III,C,1), react via two pathways. One is similar to reactions of 2-benzopyrylium salts (a), and the other resembles the behavior of isoquinolinium salts (b) (Section III, C,4,a,ii). In this case, monocyclic five-membered acyloins 198 were obtained in 15-40% yield. Obviously, their formation occurs by initial addition of amine (pathway a). The difficultly obtainable a-unsubstituted py-... 

It was suggested that for hydrogen peroxide, the reaction begins with the addition of the HOCT anion, followed by formation of the cationic intermediate 216. According to terminology, such a mechanism, which implies the presence of intermediate 105, may be called orf/io-bridging or ortho-cyclization (84UK1648), as it was described for the reaction of 2-benzopyrylium salts with sodium azide (Section III,C,2). 

The only known reaction of a 2-benzopyrylium salt with ozone leads to a destructive oxidation of the cation (51JOC1064). 

---