Background and overview[1][2]
3-Methoxyphenylhydrazine hydrochloride is 3-methoxyphenylhydrazine hydrochloride. Substituted phenylhydrazine is a very important intermediate widely used in the fields of medicine, pesticides and dyes.
Preparation[2]
Mix 3-methoxyaniline (0.50mol, 65.6g, 1eq) and 416g of 18% H2O-HCl (2.0mol, 213g, 4eq) solution evenly and cool to 0~-5°C. Weigh sodium nitrite (0.51mol, 35g, 1.02eq) and 82g water to prepare a 30% aqueous solution. Slowly add the solution dropwise to the system. After 1 hour, it is detected that there is no raw material, and the diazonium salt system is obtained. Mass spectrum: (ES-API) m/z 135(M+, 30), 107(100).
Dissolve potassium sulfite (0.87mol, 144g, 1.74eq) in 800g water, add dilute hydrochloric acid to adjust the pH to between 6-8, and lower the temperature to 0°C. Add the diazonium salt system dropwise to potassium sulfite, and at the same time, add 15% potassium hydroxide aqueous solution dropwise to control the pH between 6-8. After the dropwise addition, keep it at 0°C for 1 hour, and then heat the system at 60°C for 2 hours. Check if there is no Diazonium salt, Mass spectrum: (ES- API) m/z136 (M+, 80), 107 (100). Move the system to the reaction kettle, add 1.06g of palladium on carbon, add hydrogen and pressurize it to 4MPa, heat to 90°C, react for 6 hours, and detect.
Add hydrochloric acid (2mol, 200g, 4eq, 36%) to the system, heat at 100°C for 2 hours, the system is clarified, filtered, and the filtrate is cooled and crystallized; the system is filtered, and the wet filter cake is 130g, with a content of 63%; collect The rate is 93.8%, Mass spectrum: (ES-API) m/z 138 (M+, 30), 121 (100).
Application [1]
3-Methoxyphenylhydrazine hydrochloride can be used to prepare 4-hydroxyindole.
4-Hydroxyindole is a light yellow or white crystalline powder, slightly soluble in water and soluble in acetone. It is an important pharmaceutical intermediate and organic synthesis intermediate. CN201711068204.9 provides a preparation method for 4-hydroxyindole using 3-methoxyphenylhydrazine hydrochloride. The preparation method is simple to operate, has mild conditions, has less by-products, has high product purity and has a high product yield. . In order to achieve the above objects, the present invention adopts the following technical solutions:
(1) Dissolve 3-methoxyphenylhydrazine hydrochloride in DMF, add concentrated sulfuric acid, and mix the catalyst evenly, add acetaldehyde, control the temperature at 60-80°C, reflux for 90-120 minutes, and react After completion, filter to obtain 4-methoxyindole;
(2) Dissolve the prepared 4-methoxyindole in dichloromethane and place it in a reaction kettle. Pour in nitrogen and control the temperature at 50-70°C. Then add HBr into the solution and reflux. After reacting for 45-90 minutes, the temperature was brought to room temperature, the solvent was removed under reduced pressure, and the 4-hydroxyindole was obtained by recrystallization.
Main reference materials
[1] CN201711068204.9 A preparation method of 4-hydroxyindole
[2] CN201610936923.7 A synthesis method of substituted phenylhydrazine and its salt
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