CN104984760A - Method for preparing (S)-3,3,5-trimethylcyclohexanone, and catalyst thereof - Google Patents

Abstract

The invention discloses a catalyst for preparing (S)-3,3,5-trimethylcyclohexanone ((S)-TMCH), and a method for preparing the (S)-TMCH. The preparation method is characterized in that the (S)-TMCH is obtained through a reaction of achiral 3,3,5-trimethylcyclohexanone under the catalysis of a hydrogenation catalyst and a chiral ligand, the hydrogenation catalyst is a Pd/Al2O3 catalyst, the chiral ligand is (L)-proline, proline is dispersed on the surface of the Pd/Al2O3 catalyst, and a mass ratio of proline to the Pd/Al2O3 catalyst is 0.15-0.35. Monolayer dispersion of the surface of the solid catalyst is realized through selecting the appropriate catalyst and the appropriate ratio to solve influences of mass transfer of a polyphase reaction system on the reaction in order to obtain the (S)-TMCH product. The highly-pure chiral (S)-TMCH product can be obtained under mild conditions through optimizing TMCH kinetic resolution reaction parameters.

Description

The preparation method of one (S)-3,3,5-trimethylcyclohexanone and catalyst thereof

Technical field

The present invention relates to a kind of preparation method of chirality 3,3,5-trimethylcyclohexanone.

Background technology

Chipal compounds is owing to having special biologically active and excellent character, and in the past in the more than ten years, the synthesis of single chiral compound has become the key areas of Fine Chemical fast development.

3,3,5-trimethylcyclohexanone (TMCH) is the fine solvent of the coating such as resin, paint, varnish, and its chiral enantiomer ((S)-TMCH and (R)-TMCH) is the important intermediate of the industry such as pharmacy, spices.By can TMCH be obtained to the C=C key selective hydrogenation of isophorone (IP), but product is racemic modification TMCH, be the mixture of chirality (S)-TMCH and (R)-TMCH, to obtain single chiral (S)-TMCH or (R)-TMCH product, then need further separation.But because enantiomter is under achirality condition, chemistry and physical property do not have difference, and enantiomter is separated by very difficult traditional means, the otherness of character under its chiral conditions therefore can only be utilized to be separated.At present some are had to report abroad about being carried out asymmetric hydrogenation by IP and carrying out by TMCH the research that hydrogenation Kinetic Resolution obtains chirality (S)-TMCH or (R)-TMCH, but because this reaction system is comparatively complicated, existing result of study there is much controversy reaction mechanism, also rarely has studying in great detail about this system reaction process condition.The present invention adopts solid dispersion technology to prepare TMCH hydrogenation Kinetic Resolution catalysts, obtains highly purified TMCH quiral products.

Summary of the invention

Technical problem to be solved by this invention proposes one for the above-mentioned state of the art to prepare (S)-3,3, the method for preparing catalyst of 5-trimethylcyclohexanone and corresponding (S)-3 thereof, 3, the preparation method of 5-trimethylcyclohexanone, obtains highly purified chirality (S)-TMCH product therefrom.

The present invention solves the problems of the technologies described above adopted technical scheme:

The preparation method of one (S)-3,3,5-trimethylcyclohexanone, it is characterized in that: be obtained by reacting under hydrogenation catalyst and chiral ligand catalytic action by racemic modification 3,3,5-trimethylcyclohexanone, described hydrogenation catalyst is Pd/Al ₂o ₃catalyst, described chiral ligand is (L)-proline, proline and Pd/Al ₂o ₃the mass ratio of catalyst is: 0.15 ~ 0.35.

Above-mentioned chiral ligand (L)-proline Monolayer Dispersion is at Pd/Al ₂o ₃on catalyst surface.

Above-mentioned proline and Pd/Al ₂o ₃the mass ratio of catalyst is preferably 0.25.

The temperature prioritised of above-mentioned hydrogenation reaction is 30 ~ 55 DEG C, and pressure is preferably 1.0 ~ 2.5MPa, and the reaction time is preferably 1 ~ 10h.

Above-mentioned reaction temperature is preferably 40 DEG C, pressure is preferably 1 MPa, the reaction time is preferably 10 h.

A kind of for the preparation of (S)-3,3,5-catalyst of trimethylcyclohexanone, it is characterized in that: it comprises hydrogenation catalyst Pd/Al ₂o ₃with chiral ligand proline, described proline is dispersed in Pd/Al ₂o ₃on catalyst surface, proline and Pd/Al ₂o ₃the mass ratio of catalyst is: 0.15 ~ 0.35.

Compared with prior art, the invention has the advantages that: select suitable catalyst and proper ratio, achieve the Monolayer Dispersion of solid catalyst surface, solve multiphase reaction system because of mass transfer on reacting the impact caused, thus obtain (S)-TMCH product.

Also by optimizing TMCH Kinetic Resolution response parameter, highly purified chirality (S)-TMCH product can be obtained under comparatively mitigation condition.

Accompanying drawing explanation

Fig. 1 is the Pd/Al that the embodiment of the present invention (L)-proline is modified ₂o ₃the XRD spectra of catalyst.

Detailed description of the invention

Below in conjunction with accompanying drawing embodiment, the invention will be further described.

One, (S)-3,3,5-preparation method of trimethylcyclohexanone, comprising:

1.1 load P d/Al ₂o ₃catalyst preparing

By boehmite 700 ° of C roasting 4h in Muffle furnace that the trade mark that Yantai Heng Hui company produces is V250, obtain catalyst carrier.

Take 0.6780 g palladium bichloride, with the dissolve with hydrochloric acid solution of pH=0.04, be mixed with 40mL solution.

Take catalyst carrier 10g, by Pd salting liquid and carrier Homogeneous phase mixing, 120 DEG C of dry 10h, 500 DEG C of roasting 4 h in Muffle furnace.Calcined catalyst is with hydrogen reducing 4 h at 200 DEG C, and obtaining Pd load capacity (mass fraction) is the Pd/Al of 4% ₂o ₃catalyst.

Change palladium bichloride addition, repeat above step, prepare different loads amount Pd/Al ₂o ₃catalyst.

1.2 (L)-proline ((L)-Pro) modify Pd/Al ₂o ₃catalyst preparing

By (L)-Pro and Pd/Al ₂o ₃by XRD analysis, catalyst, with the grinding of different quality ratio, determines that (L)-Pro is at Pd/Al ₂o ₃catalyst surface deployment conditions, the results are shown in Figure 1.

The preparation of 1.4 chirality TMCH

Add 30 mL ethanol in reactor, taking Pd load capacity (mass fraction) is respectively 0.27% Pd/Al ₂o ₃the TMCH 0.84g that catalyst 2.72 g, (L)-Pro 0.68g and the uncommon love of ladder change into the production of industrial development Co., Ltd loads in reactor, hydrogen purge 10 min.Boost to 1 MPa, power-on, open stirring, start heating schedule, be warming up to 40 DEG C, reaction carries out 5 hours.

1.5 product analysis

Adopt Agilent 6820 chromatographic product composition, chromatographic condition: beta-schardinger dextrin-capillary column; Injection port carrier gas: He; Injector temperature: 250 DEG C; Post case temperature: from 50 DEG C with 5 DEG C/min temperature programming to 220 DEG C, column head pressure 34.47 kPa; Fid detector, temperature 250 DEG C.

Enantiomeric excess value is calculated by following formula:

ee%=([S]-[R])/([R]+[S])×100

Wherein: [S] is the concentration of (S)-TMCH, [R] is the concentration of (R)-TMCH.

Two, (L)-Pro is at Pd/Al ₂o ₃the dispersion of catalyst surface and catalytic reaction result

Table 1 (L)-Pro is at Pd/Al ₂o ₃the ee% value of catalyst surface dispersion, Pd granularity and product

Reaction condition: TMCH 2.80g, ethanol 100mL, 1MPa, 20 ° of C, 5h, Pd (4wt%)/Al ₂o ₃: 0.50g.

As can be seen from Figure 1, (L)-Pro and Pd/Al ₂o ₃when catalyst quality ratio is greater than 0.25, the diffraction maximum of (L)-Pro can be seen; When ratio is 0.15, on XRD spectra, the diffraction maximum of (L)-Pro disappears, and obtains (L)-Pro at Pd/Al with the extrapolation of reference intensity method ₂o ₃on catalyst, the threshold value of Monolayer Dispersion is 0.22.

In table 1, data are known, when m _pro/ m _catwhen being increased to 0.35 by 0, catalyst surface Pd granularity is increased to 5.8 nm by 3.0nm, due to the Pd granularity <10 nm on prepared catalyst surface, therefore TMCH hydrogenation Kinetic Resolution obtains chirality (S)-TMCH, proline and Pd/Al ₂o ₃the mass ratio of catalyst is: 0.15 ~ 0.35, and its ee% value is all greater than 50%, namely achieves the object of preparation (S)-TMCH, and finds m _pro/ m _catwhen being 0.25, chirality (S)-TMCH ee% value is maximum, is 80.6%.

Three, Monolayer Dispersion (L)-Pro modifies Pd/Al ₂o ₃tMCH Kinetic Resolution reaction on catalyst

Add (L)-Pro in reactor and modify Pd (0.27 wt%)/Al ₂o ₃catalyst 3.409 g( m _pro/ m _catbe 0.25), TMCH 0.841g, 30 mL ethanol, table 2 ~ table 4 is the result of TMCH Kinetic Resolution reaction under differential responses temperature, reaction pressure and reaction time condition.

As can be seen from Table 2, product (S)-TMCH ee% value raises with temperature and falls after rising, hydrogenation process heat release, and favors low temperature carries out in reaction forward, and catalyst P d/Al ₂o ₃hydrogenation activity with temperature raise and increase.The suitable temperature of preparation chirality TMCH is: 30 ~ 55 DEG C, optimal reaction temperature is 40 DEG C.

As can be seen from Table 3, in 0.2 ~ 2.5 MPa pressure limit, the ee% value of product (S)-TMCH increases with reaction pressure and increases, but during pressure >1.0 MPa, the trend that ee% value increases with reaction pressure reduces.Because the impact of pressure on (S)-TMCH-Pro and (R)-TMCH-Pro hydrogenation reaction speed there are differences, the carrying out of (R)-TMCH-Pro hydrogenation reaction is more conducive under elevated pressures, therefore, the convenient pressure of preparation chirality TMCH is: 1.0 ~ 2.5 MPa, optimum response pressure is 1.0MPa.

As can be seen from Table 4, along with the prolongation in reaction time, the ee% value of product (S)-TMCH increases gradually.After 5 h, reaction rate obviously slows down, and TMCH hydrogenation resolution reaction is close to thermodynamical equilibrium.When reaction proceeds to 10h, (R)-TMCH is converted completely, and the ee% value of product reaches 100%.Therefore, the right times preparing chirality TMCH is: 1h ~ 10 h, optimum reacting time is 10 h.

Table 2 reaction temperature affects (S)-TMCH product ee% value

Reaction condition: 1MPa; 5h

Table 3 reaction pressure affects (S)-TMCH product ee% value

Reaction pressure/Mpa 0.2 0.5 1.0 1.5 2.0 2.5
		Product ee% 30.8 38.7 49.6 53.2 55.4 54.5

Reaction condition: 40 DEG C; 1h

Table 4 reaction time affects (S)-TMCH product ee% value

Reaction condition: 40 DEG C; 1 Mpa.

Claims (7)

1. one kind (S)-3,3,5-preparation method of trimethylcyclohexanone, it is characterized in that: obtained at hydrogenation catalyst and chiral ligand catalytic reaction by racemic modification 3,3,5-trimethylcyclohexanone, described hydrogenation catalyst is Pd/Al ₂o ₃catalyst, described chiral ligand is (L)-proline, and proline is dispersed in Pd/Al ₂o ₃on catalyst surface, proline and Pd/Al ₂o ₃the mass ratio of catalyst is: 0.15 ~ 0.35.

2. (S)-3,3,5-preparation method of trimethylcyclohexanone as claimed in claim 1, is characterized in that: described chiral ligand proline Monolayer Dispersion is at Pd/Al ₂o ₃on catalyst surface.

3. (S)-3,3,5-preparation method of trimethylcyclohexanone as claimed in claim 1, is characterized in that: described proline and Pd/Al ₂o ₃the mass ratio of catalyst is 0.25.

4. (S)-3,3,5-preparation method of trimethylcyclohexanone as claimed in claim 1, is characterized in that: the temperature of described hydrogenation reaction is 30 ~ 55 DEG C, and pressure is 1.0 ~ 2.5MPa, and the reaction time is 1h ~ 10 h.

5. (S)-3,3,5-preparation method of trimethylcyclohexanone as claimed in claim 1, is characterized in that: described reaction temperature is 40 DEG C, pressure is 1 MPa, the reaction time is 10 h.

6. one kind for the preparation of (S)-3,3,5-catalyst of trimethylcyclohexanone, it is characterized in that: it comprises hydrogenation catalyst Pd/Al ₂o ₃with chiral ligand proline, described proline is dispersed in Pd/Al ₂o ₃on catalyst surface, proline and Pd/Al ₂o ₃the mass ratio of catalyst is: 0.15 ~ 0.35.

7., as claimed in claim 6 for the preparation of (S)-3,3,5-catalyst of trimethylcyclohexanone, it is characterized in that: proline and Pd/Al ₂o ₃the mass ratio of catalyst is 0.25.