Tropolone, acidity synthesis

Tropolone has been made from 1,2-cycloheptanedione by bromination and reduction, and by reaction with A -bromosuccinimide from cyolo-heptanone by bromination, hydrolysis, and reduction from diethyl pimelate by acyloin condensation and bromination from cyclo-heptatriene by permanganate oxidation from 3,5-dihydroxybenzoic acid by a multistep synthesis from 2,3-dimethoxybenzoic acid by a multistep synthesis from tropone by chlorination and hydrolysis, by amination with hydrazine and hydrolysis, or by photooxidation followed by reduction with thiourea from cyclopentadiene and tetra-fluoroethylene and from cyclopentadiene and dichloroketene. - ... 

Tlie synthesis concludes by the route pioneered by Eschenmoser. Itromination of 47 proceeds at the position a to the tropolone I ing to give 48. Displacement of halogen by ammonia followed by liase hydrolysis of the tropolone methyl ether gives trimethyl-lolchicinic acid. Acetylation of the amine followed by reesteri-... 

Numerous reactions of the betaines 86 with olefinic 1,3-dipolarophiles have been reported. lV-Methylpyridinium-3-olate (111) with electron-deficient olefins gives the adducts 112. - Alkynes give similar adducts (110) These adducts (110 and 112) are useful intermediates for tropolone synthesis. Quaternization to methiodides (113, 115) and treatment with base gives dimethylaminotropones (114) which are hydrolyzed to tropolones (116). Good syntheses of stipitatic acid (116 R = COjH, R = OH) and hinokitiol (116 R = H, R = CHMe ) have been achieved by this route (Scheme 5). Similar transformations have been achieved using the N-phenyl betaine 86 (R = Ph, R = H) which is more reactive but whose adducts are difficult to quaternize. A difference is observed when benzyne is... 

From the extensive chemical experience of the last decade in the stereochemistry and synthesis of fused ring systems related to steroids, alkaloids, resin acids, and terpenes and in the synthesis and reactions of tropolones, one might be led to the erroneous conclusion that the total synthesis of colchicine should not be difficult. Preliminary studies in this direction have been reported by many workers, but the ultimate goal has yet to be reached. 

Cyclopropanation.1 The key step in a biomimctic synthesis of (i)-colchicine (4) is a regio- and stereoselective reaction of the tricyclic I, prepared in several steps from 5-bromo-2-methoxyphenol, with dimethylsulfoxonium methylide to give a single product (2) in 75% yield. When treated with trifluoroacclic acid at 25°, this product rearranges in 89% yield to the a-tropolone O-methyl ether 3. This product is converted into ( )-co chicine (4) in four known steps. 

Following a route previously developed for the synthesis of deacetamidocolchicine, (+)-colchicine has been synthesised from (136 R = R = OMe), which was hydrolysed by acid to (136 RR = 0) and this was cyclised by boron trifluoride etherate to the acid (137). Ring-expansion of the methyl ester of (137) with trifluoroacetic acid gave a mixture of (138) and the isomeric ag-unsaturated ester, both of which, on oxidation, gave the tropolone (139), hydrolysis and decarboxylation of which gave deacetairaido-isocolchicine. Hydrolysis of (139) and treatment with diphenyl-... 

Synthesis of p-tropolone and fused heterocycle derivatives by acid-catalyzed and photoreactions of o-quinones with quinolines and benzimidazoles 06ARK(7)439. 

In a new synthesis of ( )-colchicine, the spirodiene (382) was converted by reduction of the carbonyl group, Simmons-Smith cyclopropanation, and re-oxidation with Jones reagent, into the ketone (383). This underwent internal bond cleavage with a 1,2-aryl shift on treatment with acid, the resulting tropolone (384) being convertible into ( )-colchicine. ° ... 

A recent novel synthesis of desacetamidoisocolchicine (211) employs the cyclopropyl-ketone (205) as a functionalized tropolone equivalent. Acid treatment of the acetal (207), formed by condensation of (205) with the Grignard reagent (206), led to rearrangement, via dienone (208) and spiran (209), to the tricyclic system (210). Oxidation of (210) then gave the isocolchicine (211). 

Bentley, R. Aromatic synthesis in molds formation of the tropolone stipitatic acid. Biochim. et Biophys. Acta 29, 666 (1958). 

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