Abstract
Acid-catalysed hydrogen isotope exchange reactions are one of the most widely used methods for introducing deuterium into organic compounds. However, most of the exchange reactions require high temperatures and long periods of time. It was believed that a large decrease in the reaction times could be obtained using microwave irradiation. For organic compounds to benefit from the interaction with microwaves they, or the solvent in which the reaction is to be studied, need to be polar. Alternatively, the reactants need to be made more polar and one way of doing this, which is ideal for nitrogen-containing compounds, is via protonation and the formation of ionic salts. Here are illustrated such possibilities and for the present investigation chosen substituted anilines, pyridines and fused rings have been chosen. Microwave ovens, domestic (Matsui M167 BT, 750 W) and commercial (Synthewave 402 Reactor/Prolabo) were used throughout the work. The NMR spectra were obtained using a Bruker AC 300 instrument operating at 300 MHz for 1H and 46 MHz for 2H (1H decoupled). For all compounds it was customary to obtain the 1H NMR spectra before and after microwave irradiation and to compare these with the 2H (1H decoupled) spectra. Using non-exchanging groups such as -CH3, -OCH3 etc. as internal standards, allowed the % deuteriation to be calculated. The microwave-enhanced acid-catalysed hydrogen-deuterium exchange reaction of a number of aromatic amines and nitrogen-containing heterocylic compounds has been achieved extremely rapidly (<30 min) via their hydrochloride salts. The results serve to show the considerable time saving that can be achieved using microwaves. The high purity of the readily isolated products, the good deuterium incorporation and the excellent regioselectivity are additional, attractive features of these microwave-enhanced reactions. The superheating effect of a number of organic solvents has also studied, which results in boiling points being raised by up to 36°C above their conventional values.