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

Near- and supercritical D2O 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 D2O 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 D2O (p = 300 bar, t = 2 h, T = 250–450 °C) alone and with basic or metal catalyst (Na2CO3, Pd/C). Highest isotopic purities were obtained for deuteration of eugenol (d1 = 59%) and 4-hydroxyacetophenone (d5 = 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 (d1 = 61%) and 4-hydroxyacetophenone (d5 = 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.