3-(2-Chlorophenyl)propionic acid

Chemical Properties

Synthesis

2033-24-1

89-98-5

1643-28-3

The general procedure for the synthesis of o-chlorophenylpropionic acid (3-(2-chlorophenyl)propionic acid) from cyclic (sub)isopropyl malonate and o-chlorobenzaldehyde was as follows: to a three-necked flask equipped with a dropping funnel, a reflux condenser, and a thermometer was added 85% formic acid (8 mL, 180 mmol). After cooling the solution to 5°C, triethylamine (2.7 mL, 27 mmol) was added slowly and dropwise to ensure that the reaction temperature was maintained below 10°C. Subsequently, 2-bromobenzaldehyde (7a, 5 g, 27 mmol) and Meldrum acid (3.9 g, 27 mmol) were added to the reaction system and the mixture was heated to reflux for 4 hours. Upon completion of the reaction, the mixture was cooled to room temperature and poured into pre-cooled ice water (30 mL). The resulting suspension was acidified to pH ≈ 1 with 5.5 M hydrochloric acid and subsequently placed in a refrigerator overnight. The precipitated crystals were collected by diafiltration, washed with cold water (3 × 20 mL), dried in a desiccator and the product was dissolved in chloroform (100 mL). Insoluble impurities were removed by filtration and the filtrate was concentrated to about 10 mL, after which petroleum ether (15 mL) was added with stirring and the solution was heated. After slow cooling, a white solid was precipitated. A final 4.17 g (67% yield) of the target product was obtained with a melting point of 93-95°C (literature value 99-100°C). The proton NMR spectrum of the product was in agreement with the data reported in literature [8].

References