Continuous H/D exchange of aromatic hydrocarbons using near-critical deuterium oxide

Abstract

Near- and supercritical D 2O is both a relatively cheap deuterium source and an environmentally benign solvent for batch-wise H/D exchange reactions. In this work, a new continuous flow reactor online-coupled with liquid–liquid extraction was constructed for the selective deuteration of aromatic hydrocarbons in pressurized hot D 2O at short contact times. Exchange positions were identified by GC–MS, 1H NMR, and FTIR analysis. Four aromatic hydrocarbons (eugenol, 9-fluorenone, 4-hydroxyacetophenone, and xanthone) were screened for H/D exchange in conventional batch reactors with use of near- and supercritical D 2O ( p = 300 bar, t = 2 h, T = 250–450 °C) alone and with basic or metal catalyst (Na 2CO 3, Pd/C). Highest isotopic purities were obtained for deuteration of eugenol ( d 1 = 59%) and 4-hydroxyacetophenone ( d 5 = 91%) in the absence of catalyst. 2H-labelling of these two compounds was then investigated in continuous flow experiments ( p = 300 bar, T = 250–350 °C, τ = 1–4 min). Under optimized conditions, high isotopic purities were obtained for eugenol ( d 1 = 61%) and 4-hydroxyacetophenone ( d 5 = 82%), as before in batch runs, but the contact time, and the probability of decomposition, were significantly reduced. The continuous process developed offers good potential for the deuteration of thermally sensitive substrates.