Preparation of Polyacetoxytropones and Polyhydroxytropolones by Acetolysis and Hydrolysis of Halotroponoids by Acetyl Trifluoroacetate with Exhaustive Displacement of Halogens on the Tropone Ring. Predominant Formation of Reductive Acetolysates from Fully-Substituted Tropones

Abstract

Di-, tri-, and tetrahydroxytropolones were prepared in good yields by the acetolysis of corresponding halotropones or polyhalotropolones with acetyl trifluoroacetate followed by acetic acid hydrolysis. However, using the same treatment to obtain hexaacetoxytropone with fully substituted acetoxyhalotropones predominantly yielded fewer substituted acetoxytropones than expected; the mechanism of formation was shown to involve an acetic acid-mediated reduction of intermediary formed acetoxy-p-tropoquinone equivalents. A couple of 2,7-unsubstituted 3,4-diacetoxytropones were deduced to have cyclized 1,3-dioxole structures, 2-acetoxy-2-methyl-5H-cyclohepta-1,3-dioxol-5-ones. An acetolysis of the brominated 5-isopropyltropolones furnished an acetylated by-product, 2,3,7-triacetoxy-5-(1,1-dimethyl-2-oxopropyl)tropone, which might be formed by the acylation of an intermediate, 3,4,5,6-tetraacetoxy-8,8-dimethylheptafulvene.

The biology and synthesis of α-hydroxytropolones

“…This can be done directly or through intermediate acetolysis, such as the use of an acetic anhydride/ trifluoroacetic acid/ acetic acid mixture. 40 One example demonstrating the oxidation strategy was in the total synthesis of puberulonic acid by Nozoe and coworkers from purpurogallin (Scheme 3). 41 Unfortunately, as demonstrated by the aforementioned structure-function studies of Piettre and Marquet, this route does not lend itself to ready incorporation of diverse substitution patterns.…”

Monoaryl- and Bisaryldihydroxytropolones as Potent Inhibitors of Inositol Monophosphatase

“…Work describing the use of 2 in Suzuki coupling reactions suggested it could be a convenient means to reach our target molecules. , This would be possible only if the additional hydroxyl groups can be efficiently introduced. Such a transformation is in principle possible through sequential bromination of the aryltropolone, acetolysis of the resultant bromo derivative using Takeshita's reagent (ATA; see below), and hydrolysis of the subsequent polyacetate, as shown in Scheme (steps C−E). Only one hydroxyl group at a time can be introduced since direct dibromination of tropolones is known to occur in α and γ positions .…”

3-Hydroxytropolone (2,7-dihydroxycyclohepta-2,4,6-trien-1-one)

“…Compound (I) was prepared by hydrolysis of 2,7-diacetoxytropone with aqueous 50% acetic acid (Takeshita et al, 1987). Crystals of (I) were grown from a chloroform solution by slow evaporation.…”