Synthesis of [uniformly ring-14C]-labelled 4-hydroxybenzaldehyde, vanillin, and protocatechualdehyde

[Uniformly ring-14C]-labelled 4-hydroxybenzaldehyde, vanillin, and protocatechualdehyde were synthesized from [14C]-labelled phenol, guaiacol, and catechol with methyl dichloromethyl sulfide (CH3SCHCl2) under Friedel-Crafts alkylation conditions in dichloromethane at -78 deg C for 5 min (in the case of phenol and guaiacol) or at -20 deg C for 1 min (in the case of catechol), by rapid addition of SnCl4 to mixtures of the phenolic compound and CH3SCHCl2, followed by hydrolysis with HCI. Regioselective formylation (para to the -OH group) was achieved. The conversion rates were 96, 81, and 88% for 4-hydroxybenzaldehyde, vanillin, and protocatechualdehyde, respectively, and the yields of the recovered products after work-up amounted to 88, 75, and 83%, respectively. In the case of guaiacol, 17% of isovanillin was obtained as by-product. It was found that the presence of water or ethyl acetate in the reaction mixture, at a molar ratio of 60:1 (water:guaiacol) or 120:1 (ethyl acetate:guaiacol), had little influence on the yields under the reaction conditions. Factors influencing the yields are discussed in the study.