3,5-Dimethylphenylhydrazine hydrochloride synthesis
- Product Name:3,5-Dimethylphenylhydrazine hydrochloride
- CAS Number:60481-36-9
- Molecular formula:C8H13ClN2
- Molecular Weight:172.66
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]+.
108-69-0
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60481-36-9
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Yield: 85.22%
Reaction Conditions:
Stage #1:3,5-dimethylaminoaniline with hydrogenchloride in water at 25 - 35; for 0.333333 h;
Stage #2: with sodium nitrite in water at -5 - 0;
Stage #3: with hydrogenchloride;tin(II) chloride dihdyrate in water at -5 - 35;
Steps:
7a
Preparation of 3,5-Dimethyl phenyl hydrazine hydrochloride 2220.0 ml hydrochloric acid was charged into a 5.0 L 4 necked round bottom flask connected to a mechanical stirrer, thermo meter socket, and condenser. 200.0 g (1.65 mol) of 3,5-Dimethyl aniline was charged at 25-35° C. Reaction mass was stirred for 20 min. Reaction mass was cooled to -5 to 0° C. Sodium nitrite solution [120.0 g (1.74 mol) of Sodium nitrite was dissolved in 1060.0 ml of DM Water and cooled to 0-5° C.) was added to dimethyl aniline mass at -5 to 0° C. for 60-90 min. Maintained the mass temperature at -5 to 0° C. for 60-75 min. 740.0 ml of hydrochloric acid was charged into a 10.0 L 4 necked round bottom flask connected to a mechanical stirrer, thermo meter socket, and condenser. 746.0 g of stannous chloride.2H2O (3.30 mol) was charged. Stirred the mass for 30-45 min at 25-35° C. Reaction mass was cooled to -5 to 0° C. The diazotized solution was added slowly to stannous chloride solution at -5 to 0° C. for 150-180 min. Maintained the mass temperature at -5 to 0° C. for 30-45 min. Reaction mass temperature was raised to 25-35° C. Maintained the mass temperature at 25-35° C. for 90-120 min. Solid was filtered and solid was washed with 200.0 ml of water. Compound was dried under vacuum at 55-60° C. 1000.0 ml of ethanol and crude compound were charged into a 2.0 L 4 necked round bottom flask connected to a mechanical stirrer, thermo meter socket, and condenser. Raised the mass temperature to reflux temperature. Maintained the mass temperature at reflux for 30-45 min. 20.0 g of carbon was charged and maintained the mass temperature at reflux for 30-45 min. Carbon was filtered and carbon was washed with 200.0 ml of ethanol. Collected the filtrate into a flask. Distilled off ethanol completely under vacuum at mass temperature not crossing 60° C. Mass temperature was cooled to 25-35° C. and release the vacuum. 800.0 ml of isopropyl ether was charged. Maintained the mass temperature at 25-35° C. for 45-60 min and mass temperature was cooled to 0 to 5° C. Maintained the mass temperature at 0 to 5° C. for 45-60 min. Solid was filtered and solid was washed with 200.0 ml of isopropyl ether. Compound was dried under vacuum at 45-50° C. till obtaining constant weight. Dry weight of the compound weight: 243.0 g (yield 85.22%) Purity by HPLC: 99.6%, 3.5-Dimethyl content by HPLC is 0.13% Spectral data: FT-IR (K Br) (cm-1): 3237, 3118, 3008, 2919, 2662,1608, 1588, 1577, 1533, 1518, 1308, 1276, 1159,1061, 684, cm-1. 400 MHz 1H NMR (DMSO-d6): δ value (ppm): 2.20 s (2-CH3), 2.49 s (NH2), 6.58 s (Ar-Ha, Hb, Hc. 8.10 broad (NH), 10.09 broad (HCl).13C NMR δ value: 21.11(2C), 112.33(2C), 123.02(1C), 137.98(2C), 145.56(1C).Mass: 137.26 [M]+1, -HCl, 121.20 [M-NH2]
References:
Natco Pharma Limited US2010/298351, 2010, A1 Location in patent:Page/Page column 31
556-96-7
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60481-36-9
158 suppliers
$22.00/1g