Synthesis and biological activity of 5-(adamant-1-yl)salicylic acid, 3-(4-hydroxyphenyl)adamantanecarboxylic acid and some of their derivatives

Synthesis of Adamantylated Salicylic Acids

“…5-(Adamantan-1-yl)-2-hydroxybenzoic acid (7a) was synthesized from 4.56 g (30 mmol) of 2a and 4.35 g (31.5 mmol) of 1 in 19.5 mL (255 mmol) of TFA at 90±5°C (6 h). Yield 6.2 g (76%), white solid, mp 254-256°C (from toluene); published data [7]: mp 263-264°C. 1 H NMR spectrum (DMSO-d 6 ), δ, ppm: 1.63-1.65 m (6H), 1.74 br.s (6H), 1.96 br.s (3H), 6.85 d (1H, J = 8.0 Hz), 7.47 d.d (1H, J = 4.0, 8.0 Hz), 7.66 d (1H, J = 4.0 Hz).…”

“…A mixture of adamantan-1-ol (0.6 g, 4 mmol) and salicylic acid methyl ester (0.6 g, 4 mmol) in TFA (2.5 mL, 34 mmol) was heated at 95±5°C for 5 h. The mixture was treated with water and extracted with methylene chloride, the extract was dried and evaporated, and the residue was recrystallized from heptane. Yield 1.86 g (25%), white solid, mp 110-113°C; published data [7]: mp 113-115°C. 1 H NMR spectrum (CDCl 3 ), δ, ppm: 1.73-1.78 m (6H), 1.88 br.s (6H), 2.11 br.s (3H), 3.96 s (3H, CH 3 ), 6.94 d (1H, J = 8.0 Hz), 7.50 d.d (1H, J = 4.0, 8.0 Hz), 7.78 d (1H, J = 4.0 Hz), 10.62 s (1H, OH).…”

“…There are almost no data on the synthesis and biological activity of salicylic acid derivatives containing an adamantane fragment. It is only known that 5-(adamantan-1-yl)salicylic acid can be obtained from 1-bromo adamantane and salicylic acid (10 equiv) at 170°C [7]. This compound was found to exhibit moderate fungicidal and antibacterial activity but neither analgesic nor anti-inflammatory properties.…”