2-Benzopyrylium salts formation

The related synthesis of benzopyrylium salts involves the condensation of salicylaldehydes with methyl ketones in a basic medium, which affords the unsaturated ketone (642). Cyclization occurs on treatment with acid. The same benzopyrylium salt is formed rapidly and in high yield if the condensation is effected under acidic conditions (Scheme 252) (73BSF3421). It has been proposed that the latter synthesis proceeds via an aldol condensation accompanied by the formation of a hemiacetal, followed by dehydration. 

The use of o-hydroxyacetophenone in place of salicylaldehyde leads to the formation of 4-substituted benzopyrylium salts. 

Competing Reactions in the Formation of 2-Benzopyrylium Salts upon... 

Upon acylation of some benzyl carbonyl compounds (25, R = H, Me 51, R = OH) dibenzo[a,tropylium salts 65 have been isolated in low yields (5-15 %) along with the major products, 2-benzopyrylium salts. Veratryl acetone 25 (R = Me) as well as homoveratric aldehyde 25 (R = H) (or carboxonium ions 31 which are formed from them) may undergo an oxidative a-cleavage, resulting in the benzyl cation 64. The formation of the same cation from homoveratric acid 51 is the result of decarbonylation of the acylium ion 63. Further interaction of the benzyl cation 64 with the substrate, followed by cyclization and oxidation, results in the polycyclic tropylium salts 65 (82ZOR589). 

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... 

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... 

The easier nucleophilic addition to 2-benzopyrylium salts, compared with monocyclic analogs, leads to loss of selectivity by the cation towards nucleophiles present in the mixture when they possess approximately equal nucleophilicity (NH3, H20, ROH). This forms stable adducts 109 (R = Aik), under these conditions, and labile pseudobases 109 (R = H) which undergo ring opening to diketones 29. The benzo[c ]annelation also plays its role in the easy formation of anhydrobases 119, which are stabilized by two aryl rings. 

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). 

Since the decarboxylation of 161 to 162 proceeds in a poor yield, it was suggested that formation of 162 in benzene occurs directly from 2-benzopyrylium salts 62 through primary nucleophilic attack by amine in position 3. In this case, an enamine fragment of pyruvic acid appears in the ring-opened intermediate 163, which undergoes easy decarboxylation (82TL459). The vinylic carbanion 164, formed by the loss of carbon dioxide, captures a proton by intra- or intermolecular process, then hetero-cyclization takes place. 

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). 

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-... 

The clarification of the recyclization mechanism of 2-benzopyrylium salts into naphthols under the action of alkali permits some generalizations (low temperature at the beginning of reaction followed by heating, and the use of cosolvents that are unable to form stable adducts). This leads to an increase in the yield of this reaction, considered earlier (70MI1) as lacking preparative interest, similar to the formation of phenols from monocyclic pyrylium salts. Consider the example shown in Scheme 116. 

Contrary to the oxonium intermediate 115 (Section III,C,2), the intermediate 211 having the alkoxy leaving group readily opens its heterocyclic ring under these conditions. Diketones 205 (R3 is not H) thus formed are then cyclized into a-naphthols 204 (or /3-naphthols of type 209). If anhydro-bases 212 were formed, they would have to take part in the analogous conversions described previously. Obviously, the same mechanism may be applied to the scheme of formation of a-naphthols 204 from 2-benzopyrylium salts under the action of dimethylamine hydrochloride in ethanol (77KGS996) (cf. Section III,C,4,a,iv). 

The formation of a- or /3-naphthols also occurs in the interaction of aqueous alkaline solutions with cyanide adducts of 2-benzopyrylium salts, i.e., cyanoisochromenes 108 (88T6217), and the yields of naphthols obtained this way are higher than on recyclization of the 2-benzopyrylium salts themselves. 

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). 

Only a single example of the formation of a 2-benzothiopyrylium salt 223 from its oxygen analog 222 is known (76KGS858 77TH1). The 2-benzopyrylium salt 222, having an electron-withdrawing substituent in the cation, takes part in the recyclization without dimerization. 

Evidently, deprotonation of adduct 112 precedes the ring opening. Unlike monocyclic pyrylium salts, only one pathway may be followed for the adducts of 2-benzopyrylium salts with the nucleophile possessing two carbon atoms, both of which might participate in the construction of the new skeleton. That the added component does not react as a 1,1-nucleophile may be explained by the difficult formation of intermediate 226, since it should be a fixed orf/zo-quinonoid form. 

For monocyclic pyrylium salts, the realization of an alternative pathway is equally possible [82ACH(Suppl)]. But for 2-benzopyrylium salts, even in the reaction with nitromethane, which is able to act only as a 1,1-nucleophile, the formation of naphthalene 228 was not more than 5%, whereas adduct 227 was isolated quantitatively (90KGS315). 

The formation of acylnaphthalenes 225 occurs under mild conditions (catalysis by sodium rm-butoxide or with the use of the phase-transfer method and TEBA as catalyst), and it affords high yields (60-90%). In this connection, it is surprising to recall the opinion about the incapability of 2-benzopyrylium salts to take part in recyclization reactions with compounds possessing active methylene groups, with secondary amines, or with sulfur or phosphorus nucleophiles (71CB2984). 

The only competing reaction in interactions of 2-benzopyrylium salts with active methylene compounds is the formation of naphthalene 229, which is constructed with participation of the 1-methyl group of the ben-zo[c]pyrylium cation (90KGS315). 

A classical type of dimerization of heterocyclic compounds is the formation of a twin molecule consisting of the same fragments. Such a reaction is known for 2-benzopyrylium salts. Thus, the reduction of the 2-benzopyry-lium salt 261 by zinc dust leads to the intermediate radical 262, which is dimerized in situ to the bisisochromene 263 (76KGS999) (cf. Section IV, B). 

Therefore, most probably, the formation of chrysenes 246 from 2-benzopyrylium salts occurs via the process of a-1 dimerization. At the same time, one cannot exclude the action of anhydrobase 267 as dieno-phile, which leads to its addition to positions 1 and 4 of the initial 2-benzopyrylium cation by analogy with [4 + 2] cycloadditions in reaction with ethyl vinyl ether (Scheme 14) (cf. Section III,D,1). 

The formation of anthracene 278 (Ar = Ph) directly from the corresponding 2-benzopyrylium salt 30 occurs in low yield, and the final result is dependent both on the nature of the alcohol used and on the concentration of the alkaline solution. Thus, on treatment of this salt 30 with 2% aqueous alkaline solution, 0-naphthol 209 was the only product, whereas with 50% concentration of alkaline solutions, anthracene 278 was formed, but in a yield of less than 20%. A somewhat better yield (40%) of 278 (Ar = Ph) was reached on carrying out the conversion of 2-benzopyrylium salt in isopropyl alcohol containing sodium isopropoxide. However, one can conclude that independent of conditions, the formation of anthracene 278 from 2-benzopyrylium salt in alkaline media does not occur via the intermediate diketone 29 (R1 = Me, R3 = Ph). This is because the latter compound gives rise only to j3-naphthol 209 under the reaction conditions. 

Scheme 15. On treatment of 2-benzopyrylium salts 280 with DMF, the formation of dimers 281 is accompanied by disproportionation to a small degree, as described in Section III, F,2,d.

Probably the formation of naphthalenes 287 and 288 from dimers 276 occurs in the presence of acids, in accordance with the mechanism proposed for acid-catalyzed transformations of adducts formed from 2-benzopyrylium salts and acetoacetic ester 235 (cf. Section III,C,4,d). 

Although some radicals and cation radicals are postulated for chemical and electrochemical transformations of 2-benzopyrylium cations (Sections III,F,1 and IV,B)> attempts to record their electron spin resonance (ESR) spectra failed, obviously because of a low stability of these radicals. However, the structural combination of hydroxy aryl and 2-benzopyrylium fragments favors the formation of radical cations 301-303, and their ESR spectra were recorded on oxidation of the corresponding 2-benzopyrylium salts with lead tetraacetate (87RRC417). 

Similar to aroxyl-benzo[b]pyrylium systems (78ZOR1643), there is no detectable delocalization of the unpaired electron on the benzo[c]pyrylium ring in 301-303 (87RRC417). The stability of the radical cation is determined in this case by the position of the aroxyl substituent in the cation, and the most stable is 301. The formation of diradical species 303 together with the monoradical cation, was indicated on oxidation of the corresponding 2-benzopyrylium salt. 

The 2-allyl-277-chromene derivative 73 is synthesized from 477-chromen l-one by in situ formation of the 4-silyloxy-benzopyrylium salt 74 followed by reaction with allyltri- -butyltin (Scheme 25) <2001T1005>. 

Porco s team reported the formation of benzopyrylium salts 29 (Scheme 5.14) from the action of silver and gold catalysts on o-alkynylbenzaldehydes 28.54 Although this reaction proceeds much faster with gold than with silver, the benzopyrylium formation is of interest and will be discussed further. 

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