3,5-Dimethylphenylhydrazine hydrochloride

108-69-0

60481-36-9

1. 2220.0 mL of hydrochloric acid was added to a 5.0 L four-necked round-bottomed flask fitted with a mechanical stirrer, thermometer socket and condenser. 2. 200.0 g (1.65 mol) of 1-amino-3,5-xylene was added to the flask at 25-35 °C and stirred for 20 minutes. 3. cool the reaction mixture to -5 to 0 °C. 4. a sodium nitrite solution was prepared by dissolving 120.0 g (1.74 mol) of sodium nitrite in 1060.0 mL of deionized water at 0-5°C and cooled to 0-5°C. 5. the sodium nitrite solution was slowly added to the reaction mixture, maintained at -5 to 0 °C, and reacted for 60-90 min. 6. 740.0 mL of hydrochloric acid was added to a 10.0 L four-necked round-bottomed flask fitted with a mechanical stirrer, thermometer socket and condenser. 7. 746.0 g (3.30 mol) of stannous chloride dihydrate was added and stirred at 25-35 °C for 30-45 min. 8. Cool the reaction mixture to -5 to 0 °C. 9. Add the diazotization solution slowly to the stannous chloride solution at -5 to 0 °C for 150-180 minutes. 10. maintain the reaction mixture at -5 to 0°C for 30-45 minutes. 11. Increase the temperature of the reaction mixture to 25-35°C and hold for 90-120 minutes. 12. Collect the solid by filtration and wash with 200.0 mL of water. 13. Dry the solid under vacuum at 55-60 °C. 14. Add 1000.0 mL of ethanol and crude product to a 2.0 L four neck round bottom flask fitted with a mechanical stirrer, heating jacket and condenser. 15. Heat to reflux and hold for 30-45 minutes. 16. 20.0 g of activated carbon was added and reflux was continued for 30-45 minutes. 17. Remove activated carbon by filtration and wash with 200.0 mL of ethanol. 18. Collect the filtrate and remove ethanol by vacuum distillation at no more than 60°C. 19. Cool to 25-35°C and release vacuum. 20. 800.0 mL of isopropyl ether was added and kept at 25-35°C for 45-60 minutes, then cooled to 0-5°C. 21. Hold at 0-5 °C for 45-60 minutes, filter to collect solids and wash with 200.0 mL isopropyl ether. 22. The solid was dried under vacuum at 45-50 °C to a constant weight. 23. 23. Dry weight of product: 243.0 g (85.22% yield), HPLC purity: 99.6%, 3,5-dimethyl content: 0.13%. 24. Spectral data: FT-IR (KBr, cm^-1): 3237, 3118, 3008, 2919, 2662, 1608, 1588, 1577, 1533, 1518, 1308, 1276, 1159, 1061, 684. 400 MHz 1H NMR (DMSO-d6): δ 2.20 (s, 2- CH3), 2.49 (s, NH2), 6.58 (s, Ar-Ha, Hb, Hc), 8.10 (br, NH), 10.09 (br, HCl).13C NMR δ: 21.11 (2C), 112.33 (2C), 123.02 (1C), 137.98 (2C), 145.56 (1C). MS: 137.26 [M+H]+, -HCl, 121.20 [M-NH2]+.