Stannous chloride dihydrate → 3-Chloro-2-(3'-chloropropylthio)phenyl hydrazine

Temperature

0 °C

3-Chloro-2-[(3-chloropropyl)sulfanyl]aniline (4.2 g, 15.4 mmol) was dissolved in TFA (24 mL) at 23° C. With stirring concentrated HCl (24 mL) was added. This mixture was cooled in an ice bath. A solution of NaNO2 (1.17 g, 10 mmol) in water (6 mL) was added dropwise over 10 min. The internal temperature of the reaction was maintained at <5° C. during this addition, and then maintained at 0° C. for 1 h at which time it was transfered via cannula over 10 min to a stirred solution (8 mL) of SnCl2.2H2O (7.65 g, 34 mmol) in concentrated HCl cooled in an ice bath. The cooling bath was then removed and the reaction was allowed to warm to 23° C. for 1 h. It was recooled in an ice bath. Aqueous NaOH solution (50%) was added dropwise until pH>12 affording a heterogeneous product which was treated with CH2Cl2-MeOH (20:1, 250 mL). This mixture was filtered and the resulting two-phase filtrate was extracted with CH2Cl2 (2×200 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. to afford 3-Chloro-2-(3′-chloropropylthio)phenyl hydrazine (4.0 g, 90%) as a brown oil. The resulting oil was dissolved in CH2Cl2 (100 mL),and a stream of HCl gas was bubbled into this solution for 5 min. The resultant purple solid was isolated after evaporation of the solvent to afford 1-{3-chloro-2-[(3-chloropropyl)sulfanyl]phenyl}hydrazine hydrochloride and used without further purification. 1H NMR (CD3OD, 300 MHz) δ7.37 (t, 1H, J=8.0 Hz), 7.15 (dd, 1H, J=8.1, 1.1 Hz), 6.95 (dd, 1H, J=8.5, 1.1 Hz), 3.67 (t, 2H, J=6.3 Hz), 2.95 (t, 2H, J=7.0 Hz), 1.90 (quintet, 2H, J=6.6 Hz) ppm

1. additionwas added
2. temperatureThis mixture was cooled in an ice bath
3. temperatureThe internal temperature of the reaction was maintained at <5° C. during this addition
4. temperaturecooled in an ice bath
5. customThe cooling bath was then removed
6. temperatureto warm to 23° C. for 1 h
7. customIt was recooled in an ice bath
8. additionAqueous NaOH solution (50%) was added dropwise until pH>12
9. customaffording a heterogeneous product which
10. filtrationThis mixture was filtered
11. extractionthe resulting two-phase filtrate was extracted with CH2Cl2 (2×200 mL)
12. dry with materialThe combined organic extracts were dried (MgSO4)
13. concentrationconcentrated in vacuo

ORD record

ord-9aea8a40aaec4a4ba87bb8af4a055f85

Source dataset

uspto-grants-2004_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06713471B1