Efficient <i>ortho</i>-Oxidation of Phenols with Diacyl Peroxides

Abstract

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...

Syntheses of Carnosic Acid and Carnosol, Anti-oxidants in Rosemary, from Pisiferic Acid, the Major Constituent of Sawara

“…The spectroscopic data of the isolated pisiferic acid were identical with those of the authentic pisiferic acid. 9,10) The oxidation of pisiferic acid was examined with three reagents, meta-chlorobenzoyl peroxide (mCBPO), chloroacetyl meta-chlorobenzoyl peroxide (CAMCBPO), 11) and 2-iodoxybenzoic acid (IBX). 16,17) Synthesis of Carnosic Acid (2) via Oxidation with mCBPO Pisiferic acid 1 was treated with 3 molar equivalents of mCBPO in methylene chloride for 16 h at ambient temperature.…”

“…Carnosic acid 2 has an additional phenolic hydroxyl group at C11. Previously we reported an efficient orthooxidation of phenols with meta-chlorobenzoyl peroxide (mCBPO) 11) and the synthesis of an anti-microbial diterpene, abietaquinone methide, active against drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). 12,13) In this report, we describe the facile synthesis of the major antioxidant in rosemary, carnosic acid 2, from pisiferic acid 1, which is the major constituent of Sawara (Chamaecyparis pisifera).…”

Syntheses and Antibacterial Activities of Diterpene Catechol Derivatives with Abietane, Totarane and Podocarpane Skeletons against Methicillin-Resistant Staphylococcus aureus and Propionibacterium acnes

“…7) Recently, we reported an efficient ortho-oxidation of phenols using metachlorobenzoyl peroxide (mCBPO) 8) and its applications for syntheses of optical active natural catechols, 9,10) abietaquinone methide 11) (1), 8,11,13-totaratriene-12,13-diol (5), 12,13) 6-deoxymaytenoquinone (6), 14) 8,11,13-totaratriene-12,13-dione (10) 14) and maytenoquinone (14). 12,13) There are many catechols with the similar tri-cyclic system of abietane, totarane or podocarpane skeleton.…”

“…We have been interested in the implication of the isopropyl substituent on the catechol ring for the biological activities and the reactivity with oxygen. We report here the syntheses of natural abietane derivatives 15-deoxyfuerstione (3), 15,16) taxodione (2), 17,18) totarane derivatives dispermone (8), 13) 12,13-dihydroxy-8,11,13-totaratriene-6-one (9) 12) and podocarpane derivatives deoxynimbidiol (8,11,13-podocarpatriene-12,13-diol) (12), 19) nimbidiol (14). 20) The antimicrobial activities against P. acnes and MRSA of compounds 1-14 depicted in Fig.…”