Benzodioxanes 2-hydroxy

The monobenzo-fused derivatives of 1,4-dioxin, 1,4-oxathiin and 1,4-dithiin, (345), (346) and (347), can all be prepared by base-catalyzed reaction between the appropriate 1,2-disubstituted benzene and an a-haloketal via an intermediate 2-alkoxy-2,3-dihydro derivative (348). The pyrolysis of the acetoxy derivative (349) at 450°C gives (345 80%) (67ZC152). 2-Hydroxy-2-phenyl-l,4-benzodioxane, from catechol and phenacyl bromide, is dehydrated to (345) by thionyl chloride in pyridine. 

Dihydroxy-N-methylindole 142 readily reacts with DHA in aqueous solution at room temperature (64CJC1401 65JCS4728) (Scheme 34). The two hydroxy groups of the indole interact with the a-diketone function of DHA to form the 1,4-benzodioxane 144. This type of reaction appears to be general since similar interactions occur between other o-diphenols and a-diketones. The mechanism by which the 1,4-benzodioxane derivative is obtained when adrenochrome 141 is reduced with ascorbic acid to give 142 via 143 was studied. 

In the second group, 6-hydroxy-2,4-dimethyl-1,3-benzodioxane was synthesised in 72% yield by the addition of hydroquinone during 6-8 hours to a cold acetic acid solution of acetaldehyde containing concentrated hydrochloric acid and reaction at 0-5°C for 3 hours (ref.161), presumably by electrophilic substitution followed by cyclic acetal formation. 

This reaction was first reported by Borsche and Berkhout in 1904. It is the reaction for preparing 1,3-benzodioxanes from phenols and aldehydes in the presence of acid, such as HCl and H2SO4. The formed 1,3-benzodioxanes can be oxidized into lactones and converted into prodrugs of anti-inflammatory agents. It is found that an electron-withdrawing group at position 8 will decrease the stability of such dioxane system toward alkali solution—for example, 6,8-dinitro-l,3-benzodioxane was easily cleaved in 1% of KOH solution to 2-hydroxy-3,5-dinitrobenzyl alcohol, whereas 6-nitro-l,3-benzodioxane was stable to boiling in 25% aqueous alkali or alcholic potassium ethoxide. ... 

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