[Synthesis]
Example 3: General procedure for the synthesis of 3-chloro-4-fluorophenylacetonitrile (Product 3A) from compound (CAS:773837-37-9) and 3-chloro-4-fluorobenzyl bromide.
1. In a three-necked flask equipped with a magnetic stirrer, condenser and dosing funnel, water (75 mL) was added.
2. sodium cyanide (13.16 g, 268.49 mmol) was added to the flask followed by chloroform (100 mL) and the phase transfer catalyst N-benzyl-N,N-diethylethanaminium chloride (3.06 g, 13.42 mmol).
3. The mixture was vigorously stirred at 25 °C while a chloroform solution of 3-chloro-4-fluorobenzyl bromide (30 g, 134.25 mmol) was added dropwise over 30 min.
4. After the dropwise addition, the reaction mixture was continued to be stirred at 25 °C for 3 hours and then heated to 45 °C and kept there for 2 hours.
5. After completion of the reaction, it was cooled to room temperature and the organic and aqueous layers were separated.
6. The organic layer was washed sequentially with 0.5 N NaOH solution and brine, then dried with anhydrous Na2SO4, filtered and concentrated.
7. The aqueous layers are combined, treated with 1 N NaOH solution and bleach (note the exothermic reaction), and treated according to standards for the treatment of cyanide-containing waste.
8. The final pure 3-chloro-4-fluorophenylacetonitrile (Product 3A, 22.05 g, 97% yield) was obtained as an oil.
1H NMR (500 MHz, chloroform-d) data for product 3A: δ 7.39 (dd, J = 6.56, 2.29 Hz, 1H), 7.21 (dd, J = 4.43, 2.29 Hz, 1H), 7.17 (d, J = 8.55 Hz, 1H), 3.71 (s, 2H). |