Method for synthesizing trans-4-methylcyclohexylamine

Abstract

The invention provides a method for synthesizing trans-4-methylcyclohexylamine, and belongs to the technical field of chemical synthesis. The method comprises the following steps: taking cheap p-methylaniline as a raw material, taking supported ruthenium as a catalyst, adding an alkali metal promoter, and hydrogenating to obtain a 4-methylcyclohexylmethanamine cis-trans mixture; carrying out acidification to form salt, cis-trans separation, neutralization extraction and rectification on the 4-methylcyclohexylmethanamine cis-trans mixture to obtain the trans-4-methylcyclohexylamine product, wherein cis hydrochloride obtained through the cis-trans separation enters the process of cis-trans separation again through the steps of neutralization, extraction, rectification and transformation to recycle the raw material. The method has the beneficial effects that the catalyst is used repeatedly, so that the cost is reduced; the molar yield of the process of cis-trans separation reaches 42.4%,and the solvent is easy to recycle and reuse; the molar yield of the trans-4-methylcyclohexylamine reaches 65% or above, and is higher than the molar yield of the trans-4-methylcyclohexylamine synthesized by other processes reported in the literatures, the process is simple and controllable, and the quality of the product 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