A kind of method of synthesizing trans-4-methylcyclohexylamine

Abstract

A method for synthesizing trans-4-methylcyclohexylamine belongs to the technical field of chemical synthesis. It comprises the following steps: using cheap p-methylaniline as raw material, using supported ruthenium as a catalyst, adding an alkali metal promoter, and hydrogenating to obtain a cis-trans mixture of 4-methylcyclohexylmethylamine; The cis-trans mixture of amines is acidified into salt, cis-trans separation, neutralization extraction, and rectification to obtain trans-4-methylcyclohexylamine products; wherein the cis-trans separation of the cis-isomer hydrochloride is obtained by neutralization, The steps of extraction, rectification and transformation are re-entered into the cis-reverse separation process, realizing the recycling of raw materials. The present invention has the following beneficial effects: the catalyst is used mechanically for many times, reducing the cost; the molar yield of the cis-trans separation process reaches 42.4%, and the solvent is easy to recover and apply mechanically; the molar yield of trans-4-methylcyclohexylamine reaches more than 65%, It is higher than other processes reported in the literature, and the process is simple and controllable, and the product quality is stable.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for synthesizing trans-4-methylcyclohexylamine. Background technique [0002] Trans-4-methylcyclohexylamine is an intermediate in organic and pharmaceutical synthesis. One of its main uses is the synthesis of trans-4-methylcyclohexylamine isocyanate. Trans-4-methylcyclohexyl isocyanate is a key intermediate in the synthesis of glimepiride for the treatment of type 2 diabetes. The main synthesis methods are as follows: (1) reaction of amine and phosgene; Nitrogen is prepared by Cirtius rearrangement; (3) with CO 2 For the reaction of formylating reagents with amines, through POCl 3 or P 2 o 5 Dehydration preparation, method (1) is the most widely used and more suitable for industrial production. [0003] The main domestic literature reports on the method (1) use p-cresol as a raw material to generate 4-methylcyclohexanol through Ni catalyst hy...

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Problems solved by technology

[0005] There are also some foreign countries about the 4-methylcyclohexylamine cis-trans mixture forming a salt, adding methanol to dissolve, and then adding acetone, ethyl acetate and other organic solvents to crystallize and separate. The molar yield of trans-4-methylcyclohexylamine is 30 %, and the boiling points of methanol, acetone and ethyl acetate are close, so it is not easy to recycle

[0006] The main disadvantages of the above process: 1), the oxidation reaction oxidant TEMPO is expensive, and it is difficult to recycle and apply mechanically; 2), there are many steps in the synthesis reaction, and there are more than ten kinds of reagents and solvents that need to be used, and the process is complicated and the amount of waste water is large; 3). The route synthesis trans-4-methylcyclohexylamine molar yield has only about 30%, and the cost is higher; 4), methanol, acetone and ethyl acetate have boiling points close to or azeotropic, and are not easy to recycle and apply mechanically