A Selective Preparation of Highly Deuterated Hydroxybenzoic Acids

作者：Nakamura Kozo^*; Morozumi Kazuki; Amano Daisuke

来源：Letters in Organic Chemistry, 2011, 8(5): 332-336.

• Hydroxybenzoic acid
• Deuteration
• Selective preparation
• Substituent effect

A practical method to prepare selected deuterated hydroxybenzoic acids was developed. A hydroxybenzoic acid was dissolved or suspended in deuterium oxide (D(2)O), then deuterium chloride (DCl) was added to adjust the pD to 0.32, and the mixture was refluxed under nitrogen for one to six hours. After removing D(2)O and DCl by lyophilization, 2,6-dihydroxybenzoic-3,5-d(2) acid, 3,5-dihydroxybenzoic-2,4,6-d(3) acid, 3,5-dimethoxy-4-hydroxybezoic-2,6-d(2) acid, and 3,4,5-trihydroxybenzoic-2,6-d(2) acid were obtained quantitatively. Aromatic carbons with double substituent effects of hydroxy or methoxy groups were selectively deuterated. It was shown that the deuterium exchange reactions, which were electrophilic substitution reactions of deuterium cations to the aromatic carbons on the hydroxybenzoic acids, were regulated by the substituent effects. Deuteriums on all aromatic carbons were stable under a physiological condition and were detected in plasma by mass spectrometry analysis after oral administration to rats.

• 出版日期2011-6