Development of a biphasic catalytic system for Ullmann coupling hydroxylation of 2,6-dichlorotoluene

2,6-Dihydroxytoluene is a crucial chemical intermediate, but its preparation via direct Ullmann coupling hydroxylation of 2,6-dichlorotoluene presents challenges. The difficulties originate from the low water solubility and the low reactivity of 2,6-dichlorotoluene. To address these issues, this study systematically evaluated 10 surfactants and 14 ligands, including N-N, N-O, and oxamide N-N bidentate ligands, combined with three Cu(I) catalysts, to develop a biphasic system emulsified by surfactants. An impressive yield of 87.3 % 2,6-dihydroxytoluene was achieved over optimal system with 10 mmol/L cetyltrimethylammonium bromide, 10 mol % CuI, and 5 mol % 4,7-dihydroxy-1,10-phenanthroline, after 16 h of reaction at 180 °C. Analytical techniques, including microscopy, dynamic light scattering, and NMR spectroscopy studies on the microemulsion particle size distribution and the influence of cetyltrimethylammonium bromide on the proton microenvironment of 2,6-dichlorotoluene. The excellent performance of the catalytic reaction system could be attributed to the three key factors: (1) the effective catalytic action of CuI and 4,7-dihydroxy-1,10-phenanthroline; (2) the surfactant cetyltrimethylammonium bromide successfully emulsifying the oil-water biphasic system into micron- and nano-scale microemulsions, maximizing the reaction's surface area; (3) the cationic head of cetyltrimethylammonium bromide interacting with the aromatic ring of 2,6-dichlorotoluene, which enriched 2,6-dichlorotoluene and OH - at the interface, thereby enhancing the Ullmann coupling reaction.