Coumarins, rearrangement

PERKIN Coumarin Rearrangement Rearrangement of coumarins to benzofurans (see 1st edition)... 

PERKIN Coumarin Rearrangement Rearrangement of coumarins to benzofurans. 

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

Metljylcoumarone has been prepared by the cyclization of ethyl a-phenoxyacetoacetate followed by hydrolysis and decarboxylation of the resulting ethyl 3-methylcoumarilate,3 4 by debromination and rearrangement of 3,4-dibromo-4-methyl-coumarin to 3-methylcoumarilic acid followed by decarboxylation,4-6 by cyclization of phenoxyacetone with concentrated sulfuric acid,6 and by treatment of 3-coumaranone with methyl-magnesium iodide followed by dehydration of the resulting car-binol.7... 

Scheme 7.37. Oxidative twofold rearrangement sequence for the synthesis of coumarin derivatives.

Coumarins are known to have pronounced bioactivity. A rather new procedure for the synthesis of pyrrolo[3,2-c]coumarins uses a domino process in which an amine oxide rearrangement [61] is involved (Scheme 7.37) [62]. Reaction of the cou-... 

Cairns N, Harwood LM, Astles DP (1994) Tandem thermal claisen-cope rearrangements of coumarate derivatives. Total syntheses of the naturally occurring coumarins suberosin, demethylsuberosin, ostruthin, balsamiferone and gravelliferone. J Chem Soc Perkin Trans... 

For preparation of allyl coumarins and dihydrofuranocoumarins by tandem Claisen rearrangement-cyclization the usual procedures required vigorous reaction conditions, workup procedures were tedious, and long reaction times led to low yields. The rearrangement of allyloxycoumarins 48 to dihydrofuranocoumarins 49 has been optimized in good yields in a sealed Teflon containers with BF3-ether in N-methyl-... 

A new synthetic protocol consisting of sequential directed ortho metallation, crosscoupling and a carbamoyl Baker-Venkataraman rearrangement has been applied to an efficient construction of coumarins (see Scheme 10). The formation of o-nitrosobenzaldehyde during the hydrolysis of o-nitrobenzyl tosylate in aqueous acetonitrile has been presented as a strong indication that the nitro group participates in the departure of the tosylate group as shown in Scheme 11. 

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

Toda et al. reported that the topotactic and enantioselective photodimerization of coumarin and thiocoumarin takes place in single crystals without significant molecular rearrangements [49]. Molecular motion needs to be called upon to explain the photochemically activated cycloaddition reaction of 2-benzyl-5-benzylidenecyclopentanone. The dimer molecules, once formed, move smoothly in the reactant crystal to form the product crystal [50]. Harris et al. investigated the reactivity of 10-hydroxy-10,9-boroxophenanthrene in the solid state and the mechanism of the solid-state reaction was characterized by both X-ray diffraction and thermal analysis [51]. It was demonstrated that the solution chemistry of 10-hydroxy-10,9-boroxophenanthrene is different from that in the solid state, where it undergoes dimerization and dehydration to form a monohydride derivative. 

Various crown ethers have been constucted onto the 3- and 4- positions of coumarin by way of 3-diazo-2ff-lbenzopyran-2,4(3ff)-dione. Cafbenoid generation under Rh-catalysis is followed by formation of an oxonium ion by reaction with the ether solvent and a sigmatropic rearrangement completes the sequence <99T6577>. 

Perkin Rearrangement (Coumarin-Benzofuran Ring Contraction)... 

The low yield dehydrogenation stage is eliminated if an alkyne is used in place of the alkene. An improved yield of coumarin results, although the initial product from the rearrangement is a cinnamate. 

The formation of the coumarin (388) from 7-allyloxy-3-methylf avone via a Claisen rearrangement and oxidation with DDQ is of a similar nature to the previous route, though yields are considerably lower (77TL473). 

The coumarin is probably derived from the initial acylated hydroxyacetophenone which, in addition to undergoing a Baker-Venkataraman rearrangement, may cyclize through an intramolecular aldol condensation. Elimination of water then gives rise to the coumarin (Scheme 161). 

There has been some controversy about the mechanisms of the Simonis and Pechmann reactions, which still remain in doubt. It has been suggested (50BSF1132) that the condensations proceed through a common oxonium ion (467). Dehydration to the phenoxyacrylic ester (468) is followed by cyclization to the chromone whilst a rearrangement to the substituted phenol (469) subsequently affords the coumarin (Scheme 171). 

Base-catalyzed rearrangement of Af-(aryloxy)pyridinium salts (11) leads to 2-arylpyridines (12) via intramolecular attack on the ortho position of the aryloxy ring by the 2-pyridyl carbanion. When X was 3-CChMe, pyrido[3,2-J]coumarins (13 R = NO2, CN) were directly obtained in useful yields from this reaction. When in (11) X was 3-COMe and R was 4-NO2, 10-hydroxy- 10-methyl-6-nitropyrido[2,3-J]benzopyran (14) was obtained in 10.8% yield.89... 

As in five-membered heterocycles, the introduction of a carbonyl group produces a dramatic effect on the photoreactivity. Pyran-2-ones undergo other electrocyclic processes in addition to those discussed in preceding sections.213 Photorearrangement, however, does not occur in the coumarin nucleus, although a photo-Fries rearrangement of 3-benzoyloxy-6,7-... 

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