Environmentally-friendly preparation method of high-purity tetrahydrocarbazole

Abstract

The invention discloses an environmentally-friendly preparation method of high-purity tetrahydrocarbazole. The method comprises the following steps: mixing cyclohexanone with methanol / ethanol or a mixed solution comprising methanol and ethanol, carrying out heating reflux, letting in a dry HCl gas as a catalyst, slowly adding phenylhydrazine and methanol / ethanol or the mixed solution comprising methanol and ethanol, and continuously refluxing; cooling the obtained reaction solution after reaction ending to slowly precipitate products from methanol / ethanol or the mixed solution comprising methanol and ethanol in microcrystal, adding distilled water for further precipitating products, filtering the products, washing the products with distilled water to neutrality, and drying to obtain high-purity tetrahydrocarbazole, wherein the mass ratio of the added distilled water to methanol / ethanol or the mixed solution comprising methanol and ethanol is 1:0.8-1:1.5, the mass ratio of phenylhydrazine to methanol / ethanol or the mixed solution comprising methanol and ethanol is 1:5-10, and the mass ratio of phenylhydrazine to cyclohexanone is 1:1.1-1.5. The preparation method has the advantages of simple process, economy, simplicity, mild reaction condition, short reaction time, high product yield, high product purity, environmental protection and the like.

Description

technical field [0001] The invention relates to a heterocyclic compound containing a nitrogen atom, in particular to a preparation method of a tetrahydrocarbazole compound. Background technique [0002] 1,2,3,4-tetrahydrocarbazole and its derivatives are very important intermediates in the field of medicine and chemical industry, such as N -Methyltetrahydrocarbazole is an important intermediate for the synthesis of highly selective serotonin receptor antagonist ondansetron, and 2-amino-tetrahydrocarbazole-propionic acid is the important intermediate of thromboxane A 2 The key intermediate of the receptor antagonist ramatroban, 1,2,3,4-tetrahydrocarbazole can be synthesized by Raney-Ni catalytic dehydrogenation to carbazole, and carbazole is an important intermediate in fine chemicals , can be widely used in different fields such as pigments, dyes, plastics, pesticides, medicines and luminescent materials, especially for the manufacture of coupled dyes and high-grade organic...

AI Technical Summary

Problems solved by technology

Carbazole and its derivatives are synthesized by the Borsche method. The purity of the intermediate tetrahydrocarbazole is crucial for the subsequent catalytic dehydrogenation of carbazole. If impurities are present, not only will the reaction rate be slow and the yield will be reduced, but it may also easily cause catalyst poisoning.

[0006] It was Crosby U. Rogers and B. B. Corson ( J. Am. Chem. Soc ., 1947, 69(11), 2910-2911), phenylhydrazine and cyclohexanone were catalyzed by acetic acid or hydrochloric acid to synthesize 1,2,3,4-tetrahydrocarbazole in one step, but the reaction yield was only It is about 90% and the purity of the product is not high; Yu Majin et al. (Dye Industry, 1998, 35(3), 21-22) synthesized 1,2,3,4- Tetrahydrocarbazole, the yield of the crude product is about 99%, but it needs to be refined through activated carbon decolorization and ethanol recrystallization, and acetic acid is used in industry, which severely corrodes the production equipment, harsh operating environment, and serious environmental pollution; Ni Haiping and Hou Qijun (CN 102249983 A) improved the production process, using phenylhydrazine / phenylhydrazine hydrochloride and cyclohexanone as raw materials, using water as a solvent to synthesize 1,2,3,4-tetrahydrogen under the catalysis of inorganic acids Carbazole, the productive rate of its crude product is about 98%, but this method uses phenylhydrazine hydrochloride (PhNHNH 2 HCl or [PhNHNH 3 ] + Cl - ) as the raw material, it is necessary to dissociate all the HCl in the hydrochloride, otherwise the efficiency of the actual reaction and the conversion rate of the product cannot reach the reported effect, and water is selected as the solvent when the product is formed. Phenomena such as further separation and purification, especially the crystallization of the product bring trouble, long production cycle, and high production cost

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