Abstract: Phenol dearomatization is one of several oxidation reactions enabled by hypervalent iodine reagents. However, the presence of a proposed free phenoxenium intermediate in phenol dearomatization is a matter of debate in the literature. Here, we report the unambiguous detection of a free phenoxenium intermediate in the reaction of an electron-rich phenol, 2,4,6-trimethoxyphenol, and (diacetoxyiodo)benzene using UV-vis and resonance Raman spectroscopies. In contrast, we predominantly detect single electron oxidation products of less electron-rich phenols or alkoxy-substituted aromatics in their reaction with (diacetoxyiodo)benzene using UV-vis and ESR (EPR) spectroscopies. We conclude that the often-postulated free phenoxenium intermediate, while possible with highly stabilizing substituents, is unlikely to be a general mechanistic pathway in the reaction of typical phenols with hypervalent iodine reagents. The polar solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) or the use of more strongly oxidizing hypervalent iodine reagents, such as [bis(trifluoroacetoxy)iodo]benzene (PIFA) or [hydroxy(tosyloxy)iodo]benzene (HTIB), can help reduce the formation of radical byproducts and favors the formation of phenoxenium intermediates.
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EXAMPLE 12 2,4,6-Trimethoxyphenol In a 500 mL flask were placed 5.0 g (25.5 mmol) of 2,4,6-trimethoxybenzaldehyde and 127 mL of methylene chloride (0.2M). This mixture was vigorously stirred with a magnetic stir bar. To the homogeneous solution was added 6.50 mL of 30% aqueous hydrogen peroxide (64.0 mmol., 2.5 equivalents) and 3.84 mL of formic acid (101.0 mmol., 4.0 equivalents). The flask was fitted with a reflux condenser and heated to reflux for 18 hours with stirring. After cooling, 82.4 mL of 1.5N sodium hydroxide (124 mmol., 4.85 equivalents) was added to the flask. The mixture was stirred for 15 minutes. The organic layer was separated and concentrated to a residue using a rotary evaporator. The residue was combined with the aqueous solution and 54.9 mL of methanol was added. The solution was stirred for 30 minutes. The methanol was removed using a rotary evaporator. The neutral materials were removed from the aqueous residue by extracting with two 100 mL portions of methylene chloride. The solution was adjusted to a pH of 1 to 2 with concentrated hydrochloric acid. The 2,4,6-trimethoxyphenol was extracted with three 100 mL portions of methylene chloride. The organic solution containing the neutrals as well as the one containing the product were separately dried over anhydrous magnesium sulfate and filtered into tared round-bottom flasks. The methylene chloride was removed using a rotary evaporator. A total of 0.547 g of neutrals was recovered. A total of 2.72 g of the crude 2,4,6-trimethoxyphenol and 2,4,6trimethoxybenzoic acid was obtained. The 2,4,6-trimethoxyphenol was purified utilizing bulb-to-bulb distillation. A mass of 0.0974 g of 2,4,6-trimethoxyphenol as brown liquid was obtained (0.529 mmol., 2.08% yield).
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