Preparation method of 4-aminocyclohexanol

Abstract

The present invention provides a 4-aminocyclohexanol preparation method, which comprises that 4-aminophenol is subjected to catalytic hydrogenation in the presence of a catalyst on a fixed bed reactor to prepare 4-aminocyclohexanol, the catalyst is Ru-M / Al2O3, the active component of the catalyst is Ru, the auxiliary agent is M, M is one of Rh, Pd, Pt and Ni, and the catalyst is Ru-M / Al2O3. And carrying out gas-liquid separation on the product after catalytic hydrogenation, salifying the obtained liquid by using hydrochloric acid to separate out a solid, and neutralizing the solid by using alkali to obtain the trans-4-aminocyclohexanol. When the 4-aminocyclohexanol is prepared by the method disclosed by the invention, a qualified trans-4-aminocyclohexanol product with high purity and a trans-form proportion of more than or equal to 99.5% can be obtained. The catalyst used in the method is high in activity, good in selectivity and high in trans-form proportion; the catalyst is long in service life while the catalytic effect is excellent, and the catalyst can stably run for more than 1000 hours; and the reaction liquid is simple in post-treatment, high in product yield and excellent in quality.

Description

technical field [0001] The invention belongs to the field of fine chemicals, and in particular relates to a preparation method of 4-aminocyclohexanol. Background technique [0002] Trans-4-aminocyclohexanol is a kind of raw material for organic synthesis, and is an important intermediate for the synthesis of drugs such as ambroxol hydrochloride. The synthetic method of trans 4-aminocyclohexanol reported at present has following several. The first one is acetaminophenol as a raw material: this route generally obtains 4-aminocyclohexanol with a high trans-isomer ratio through steps such as hydrogenation, resolution, hydrolysis, and recrystallization. Many documents have studied this method. In order to improve the yield and selectivity. However, this route has inherent defects, that is, the reaction requires amide hydrolysis, which will produce more acetate, more wastes, and low atom economy. The second one, hydroquinone as raw materials: ammonia and hydrogen as raw materia...

AI Technical Summary

Problems solved by technology

However, this route has inherent defects, that is, the reaction requires amide hydrolysis, which will produce more acetate, more wastes, and low atom economy.

The second one, hydroquinone as raw materials: ammonia and hydrogen as raw materials, under the action of Rh homogeneous catalyst, 140 ° C, 1.6MPa reaction for 3 hours, the conversion rate of this method is greater than 99%, but trans 4-aminocyclohexane The selectivity of alcohol is only 14% (ChemCatChem(2018), 10(17), 3689-3693), and the catalyst is not easy for industrial production

The third one is 4-aminophenol as raw material: this method can directly hydrogenate aminocyclohexanol to obtain aminocyclohexanol, the steps are short, and the three wastes are less. At present, many documents and patents have corresponding reports, including: (1) Ru-based Homogeneous catalyst, potassium tert-butoxide as auxiliary agent, reaction at 170°C for 72h, yield 85%, trans-isomer selectivity 52% (ACS Catalysis (2017), 7(7), 4446-4450), but the reaction time Long, low trans-isomer selectivity, expensive catalyst, not suitable for large-scale production; (2) Pd / C as catalyst, carbonate as auxiliary agent, ketone as solvent, react at 100°C for 7h, and the yield reaches 85% (CN109942444), but this route does not mention the specific selectivity of the trans isomer, and the amount of additives added is large, and the ketone solvent used for hydrogenation will also undergo reductive amination reaction with the raw material, so this patent does not mention and the corresponding purity of the obtained product

Images