[Synthesis]
Example 1: Synthesis of N-(2,5-dichlorobenzoyl)glycine
Step I: Preparation of N-(2,5-dichlorobenzoyl)glycine
To a solution of water (120 mL) containing NaOH (12 g, 300 mmol) and glycine (18 g, 239 mmol), a solution of THF (15 mL) with 2,5-dichlorobenzoyl chloride (10 g, 48 mmol) was added dropwise over a 45-minute period, and the temperature of the reaction was controlled to be lower than 25 °C. After the dropwise addition, stirring was continued for 1 hour. Subsequently, the reaction mixture was acidified with 2.0 M HCl (125 mL), controlling the temperature below 5 °C. The precipitate was collected by vacuum filtration and the crude product was recrystallized from water to give N-(2,5-dichlorobenzoyl)glycine as a white crystalline solid (6.1 g, 52% yield). Melting point 173.3°C.
1H NMR (300MHz, DMSO-d6, δ): 12.72 (bs, 1H), 8.89 (t, J = 6.0Hz, 1H), 7.54 (m, 2H), 7.48 (m, 1H), 3.93 (d, J = 6.0Hz, 2H).
13C NMR (75MHz, DMSO-d6, δ): 41.6, 129.3, 129.6, 131.4, 132.2, 138.2, 165.9, 171.4.
MS (m/z): [M + H]+ calculated value C9H8Cl2NO3 248.0; measured value 248.0; [M + Na]+ calculated value C9H7Cl2NNaO3 270.0; measured value 270.2.
Alternative synthesis method:
To a solution of glycine (21.5 g, 286 mmol) in water (437 mL) was added 2.0 M NaOH (130 mL) and cooled to 0°C. A solution of 2,5-dichlorobenzoyl chloride (50.0 g, 239 mmol) in THF (75 mL) was added dropwise at a rate of 0 ± 10 °C at a controlled temperature. During the dropwise addition, the pH was maintained at 11.0 ± 0.2 by dropwise addition of 2.0 M NaOH using a pH controller.After the dropwise addition, stirring was continued at 0 ± 10 °C for 2 h. The pH of the solution was maintained at 11.0 ± 0.2 by dropwise addition of 2.0 M NaOH using a pH controller. Subsequently, the solution was acidified to pH 2.5 with 2.0 M HCl (176 mL), the precipitate was collected by filtration, washed with cold water (125 mL), and dried under vacuum at 45 °C to afford N-(2,5-dichlorobenzoyl)glycine as a white solid (57.6 g, 97.3% yield). |