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