Pyrano benzopyrans

The base-catalyzed reaction of 4-hydroxycoumarin 184 with indolones 213 or with isatin and MN 27a on short heating leads to spiro pyrano-benzopyrans 220 (89JHC1097, 05RCB992, 08JCO741, 08RCB2373) (Scheme 82). 

This synthesis involves Michael cycloaddition reaction of the readily available 4-hydroxycoumarine 1 with a cyanocrotonitrile 2 in ethanolic piperidine to afforded 2-amino-3-cyano-4-methyl-4H, 5H-pyrano-benzopyran-5-one (3). Treatment of 3 with acetic anhydride for 0.5 h and/or 3 h under reflux afforded N-acetyl and [l]benzopyrano[3/,4/ 5,6]pyrano(2,3-d) pyrimidine-6,8-dione derivatives (4) and (5a), respectively. Also, interaction of 3 with benzoyl chloride or formic acid gave the corresponding pyrimidine derivatives (5b,c) while its treatment with formamide afforded the aminopyrimi-dine derivative (6). 

Pyrano[3,2-c]benzopyran-2,5-diones synthesis, 3, 808 Pyranobenzopyranones crystal structures, 3, 623 Py rano[3,2-c][ 1 ]benzopyran-2-ones synthesis, 3, 797 Pyranobenzothiazoles mass spectra, 3, 615 Pyrano[2,3-y]benzoxazine synthesis, 3, 714... 

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

The pyrano[3,2-c][l]benzopyran system is available from the reaction between salicylaldehyde and 5-phenylthio-4-penten-l-ols which proceeds by an intramolecular cycloaddition of an o-quinone methide desulfurisation is facile (Scheme 29) <00TL2643>. Mild conditions have been established for the synthesis of (-)-hexahydrocannabinol 50 from the olivetol derivative 49 which also involves a quinone methide (Scheme 30) <00SC1431>. 

In other somewhat related work, the synthesis of pyrano[2,3-c]azepines (and pyrido[2,3-c]azepines has been described. Reaction of hydrazoic with iV-(5,6,7.8-tetrahydro-2,5-dioxo-2W-l-benzopyran-3-yl)benzamide (or 8-hydrazono) derivatives afforded pyrano[2,3-c]azepines, which in turn can be transformed to pyrido[2,3-c]azepines <00H(53)1111>. 

There are a number of examples of the synthesis of chromans using o-quinone methides as the heterodiene in a hDA reaction. Both pyrano[3 -c]-benzopyrans and cyclopenta[c][l]benzopyrans result from an intramolecular cycloaddition of a substituted o-quinonemethide generated under mild conditions. In the former case, salicylaldehyde and an unsaturated alcohol yield the rra/is-fused tetrahydropyranobenzopyran (Scheme 10) <99JOC9507>. However, the latter synthesis (Scheme 11) is less selective <99BCJ73>. 

Pyrano-fused heterocycles, namely pyrano[3,2-f]quinoline-2,5(6//)-diones, pyrano[3,2-f]benzopyran-2,5(6//)-dione, and pyrano[3,2-f]pyridine-2,5(67T)-diones, have been efficiently prepared by the condensation of 4-hydroxy-2-(l//)-quinolines, 4-hydroxycoumarin, or 4-hydroxy-(17/)-pyridone with a-acetyl-y-butyrolactone or the sodium salt of a-formyl-y-butyro-lactone in the presence of ammonium acetate <1999JHC467>. 

The enaminones (342) also react with dichloroketene, forming 3,4-dihydropyranones (80JHC61). Dehydrochlorination with triethylamine gives the substituted pyrano[3,2-c]-[l]benzopyran-2-ones (343 Scheme 105). Yields are notably better when at least one of the substituents on the amine is aromatic. 

The reaction of 2,2-dimethyl-4,6-dioxo-l,3-dioxane (Meldrum s acid 394) and its analogues with 3-dialkylaminophenols has been used to prepare some fluorescent 7-dialkylamino-4-hydroxycoumarins (Scheme 127) (77M499). The substituted malonic acid (395) or its dehydration product is a possible intermediate, since it is known that diaryl-malonic esters are accessible from phenols and the 1,3-dioxane. 3-Methoxyphenol yields the pyrano[3,2-c]benzopyran-2,5-dione (396) in this reaction, presumably by annelation of another ring on to initially formed 4-hydroxy-7-methoxycoumarin. 

When 3-(4-j -tolyloxybut-2-ynyloxy)[l]benzopyran-2-one 1 was heated under reflux in carefully purified chlorobenzene, the exclusive product, formed in 92% yield, was 1 -(p-tolyloxymethyl)pyrano[2,3-c][l]benzopyran-5(3i/)-one 2. The compound 2 was also the exclusive product when either xylene or ethylbenzene was used as solvent. However, when 1 was heated under reflux in chlorobenzene containing a catalytic amount of AIBN, 2 was obtained in 20% yield together with 80% of 2-methyl-l-(p-tolyloxymethyl)furo[2,3-c] [l]benzopyran-4-one 3. The compound 3 was the exclusive product when PEG-600, IV.lV-dimethylaniline, pyridine or ethylbenzene containing a catalytic amount of p-TsOH was used as solvent, the yields being 90,90, 80 and 90% respectively. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

Treatment of 2-amino-4-(4 -chlorophcnyl)-3-cyano-4H,5H-pyrano[3,2-c][l] benzopyran-5-one (22) [54,55] with triethyl orthoformate in acetic an-... 

Triflates of transition metals catalyse the reaction between alkenes, salicylaldehydes and trimethyl orthoformate (TMOF) that is particularly useful for the synthesis of fused chromans. Generation of an o-quinone methide and its capture by the alkene is the key feature. The examples in Scheme 4 are illustrative. Tran.v-fused pyrano[3,2-c]benzopyrans... 

The value of 4-hydroxycoumarin in synthesis has been discussed <07THC(11)283> and its use in the synthesis of 3,4-disubstituted coumarins has been reported <07JOC7279>. The 3-arylation of 4-hydroxycoumarins, achieved using aryllead triacetates, sets up a substrate for a cascade of reactions which leads to the [2]benzopyrano[4,3-c][l]benzopyran system <07JOC3293> and the EDDA-catalysed reaction of 4-hydroxycoumarin with a,[3-unsaturated arylaldehydes produces pyrano[3,2-c]benzopyran-5-ones <07T10025>. Propargylation and... 

Watanabe, T., Kaiayama, S., Nakashita, Y.. and Yamauchi, M., Rcgiospccilic (biogenctic-type) synthesis of 2-methyl-5Fl-pyrano(3,2-clll]benzopyran-4-onc, the basic skeleton in citromycetin,/ Chem. S(k. Chem. Commun.. 761, 1981. 

The aim of this review is to survey the advances in the chemistry of chrom-3-enes (2//-l-benzopyrans, chrom-/l -enes, a-chromenes) in the last decade. This subject was previously summarized by Wawzonek in 1951. A brief but clear treatment of chrom-3-ene chemistry can be found in Dean s book (1963), where a detailed account is given of all the natural products known at that time. A section of a recent book on the synthesis of natural compounds has been dedicated to chromenes. The present review will not deal with chrom-2-enes, nor with benzo-pyrylium salts, nor with ring-fused pyrano-heterocycles. The reader... 

Knierzinger, A., and Wolfbeis, O.S., Syntheses of fluorescent dyes. Part 9. New 4-hydroxycoumarins, 4-hydroxy-2-quinolones, 27/,57/-pyrano[3,2-( ]benzopyran-2,5-diones and 27/,57/-pyrano[3,2-c]qiiin-oline-2,5-diones, J. Heterocycl. Chem., 17, 225, 1980. 

Bhavsar and his co-workers reported the formation of pyrano[2,3-a] acridin-2-ones, such as 199, from 8-aroyl-7-hydroxy-benzopyran-2-ones,... 

Hetero-/-fused derivatives of indeno[/i]benzopyrans result from the chromenylation of fluoreno[3,4-()][l]benzofuranols and related S andNMe analogues. The furo- 25 and thieno-26 [2,3-7]benzopyrans show absorption bands between 450 - 530 nm and 550 - 640 nm according to the substituents on the gem diaryl function and generally appear as various shades of brown. The half-lives vary between 1 and 6 minutes, with the thiophene analogues exhibiting faster fade rates than the furan derivatives. The closed form of the sole pyrano-... 

The pyrano[3,2-c]xanthen-7-one exhibits the two absorption bands associated with a heteroatom at a peri position of the benzopyran nucleus. Pyrano[2,3-a]xanthen-12-one 44, in which the fusion of the chromone ring is reversed, shows an intense single band blue-shifted some 14 nm relative to 2,2-diphenyl-2//-naphtho[l,2-6]pyran [Xmax 403, 482 nm (PhMe)]. Both isomers are readily degraded <01HCA117>. It is noteworthy that 44 could not be... 

Good yields of chromans, dihydrocoumarins and their benzologues result from the Au-catalysed cyclisation of terminal sulfonate esters of alkyl aryl ethers (Scheme 9) <04JA13596> and Bi(OTf)3 catalyses the reaction between salicylaldehydes and 2,2-dimethoxypropane which leads to 2,4-dimethoxy-2-methylchromans with one diastereomer being produced in large excess (Scheme 10). Pyrano[2,3-6]benzopyran has been obtained in a similar manner <04TL9369>. 

Suitably 3-substituted chromones take part in cycloaddition reactions. 3-Acyl derivatives react with 1-alkoxyalkenes in an eiu/o-selective fashion to form pyrano[4,3-/ ][l]benzopyran-10-one derivatives from which a range of chromones and chromanones can obtained (94T11755). 

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