There are many natural catechols which show various biological activities, e.g., anti-oxidant, 1) anti-methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE),2) anti-tubercular, 3) anti-bacterial, [4][5][6][7][8][9] anti-plasmodial, 10) anti-viral, 11,12) anti-tumor, [13][14][15] and anti-platelet 16) activities. Natural catechol derivatives are easily oxidized by oxygen or chemical reagents. Benzeneseleninic anhydride, 17) 2-iodoxybenzoic acid (IBX) 18,19) and iodobenzene diacetate 20,21) are well known reagents for ortho-oxidation of phenol to give ortho-quinone or ortho-hydroxy-para-quinone methide, although sometimes a complex mixture is formed. Dibenzoyl peroxide is commonly used as an initiator of polymer synthesis and an effective reagent for ortho-oxidation of phenols to give catechol monoesters. However, dibenzoyl peroxide is unstable and has caused large explosions in industrial plants, e.g., at Itabashi in Japan (1990) and in northern Taiwan (2001). 22) In the previous synthesis of abietaquinone methide 3) (1) with anti-MRSA and anti-VRE activities, we reported ortho-oxidation of phenols using a stable diacyl peroxide, m-chlorobenzoyl peroxide (mCBPO, 2) which was synthesized from meta-chloroperbenzoic acid.23) The ortho-oxidation of a diterpene phenol with mCBPO gave the corresponding catechol ester in moderate yield, but the oxidation of other small phenols gave lower yields. We thus planned to improve the ortho-oxidation of phenols with diacyl peroxides, a stable and nontoxic reagent. We report herein a novel ortho-oxidation reaction of phenol using the asymmetric diacyl peroxide which was synthesized from m-chloroperbenzoic acid, together with the improvement of the yield of ortho-oxidation of phenols with the symmetric diacyl peroxide, mCBPO.ortho-Oxidation of Phenols with the Symmetric Diacyl Peroxide, mCBPO Previously, we synthesized abietaquinone methide 1, via the ortho-oxidation of ferruginol (3) with mCBPO at ambient temperature (Fig. 1).23) Some small phenols, e.g. o-cresol, m-cresol, p-cresol, 2,4-xylenol and 3,5-xylenol, however, were not oxidized with mCBPO at ambient temperature. Kubota and Takeuchi reported the unexpected formation of mCBPO 2 by the heating of mCPBA in dimethyl formamide (DMF) which was accompanied by an explosion.24) The formation of mCBPO after the explosion indicates that mCBPO is stable under high temperatures. In fact, solid mCBPO melts at over 110°C and exhibits slow foaming when heated in a glass tube. They also foresaw that severe explosion of mCBPO in DMF over 125°C from the differential thermal analysis, and improvement of the reaction condition using CH 2 Cl 2 solution to avoid the incident. Thus we tried the reaction of phenols with mCBPO at refluxing temperature of CH 2 Cl 2 and CHCl 3 . Phenols were safely oxidized with mCBPO even at refluxing temperature in chloroform. The reaction mixtures were reduced with LiAlH 4 (LAH) and then acetylated with acetic anhydride and pyridine. The mixture was chromatographed on s...
