[612-14-6] · C8H10O2 · 1,2-Bis(hydroxymethyl)benzene · (MW 138.17)
(reagent for the protection of carbonyl groups as benzodioxepin acetals)
Alternate Name: 1,2-benzenedimethanol.
Physical Data: mp 64-65 °C.
Solubility: sol most organic solvents.
Preparative Methods: commercially available.
The title reagent (1) has been used as a protecting group for ketones and aldehydes by their conversion to the corresponding benzodioxepin. It offers the advantage of being removable under neutral conditions by hydrogenation, as opposed to other acetal protecting groups which are typically removed under acidic conditions. With simple ketones the diol is not effective in the formation of the acetals using common acids as catalysts as the yields are low. However, conversion of the diol to the corresponding orthoformate followed by treatment of the orthoformate with acid in the presence of a ketone or aldehyde provides the acetal in good to excellent yield (eq 1).1 This reaction works with a wide variety of substrates, except very hindered ketones such as camphor.
Alternatively, the use of sulfonated charcoal has been shown to be effective with the diol as a starting material (eq 2).2
This reagent has been used as a protecting group for diethyl b-oxoglutarate, which was used in the synthesis of semivioxanthin (eq 3).3 Other protecting groups failed due to difficulties encountered in their cleavage. Interestingly, in this case the authors chose to use the diol and tosic acid to obtain the acetal, but in poor yield (36%).
In the synthesis of an analog of myo-inositol 1,4,5-triphosphate, this group was used as a protecting group for a ketone as well as for a phosphoramidite. Thus treatment of the Birch reduction product of anisole with acetic acid and (1) provided the protected ketone (eq 4) which was converted to the requisite triol. This was coupled with the phosphoramidite derived from (1) and oxidized to the corresponding phosphotriester which was then cleaved to the desired phosphate (eq 5).4
The earliest use of this reagent as a protecting group was in the synthesis of cyclopropanone hydrate. The synthesis required the use of a protecting group that could be removed under neutral conditions. Thus transacetalization of the diethyl acetal derived from bromoacetaldehyde with (1) provided the benzodioxepin which was converted to the desired cyclopropane derivative (eq 6).5
University of Colorado, Boulder, CO, USA