阅读说明：本技术 一种制备r-香茅醛的方法 (Method for preparing R-citronellal ) 是由 董菁 于磊 张永振 黎源 于 2020-07-22 设计创作，主要内容包括：本发明提供一种制备R-香茅醛的方法,基于本发明的方法能够显著提高催化剂的催化活性和稳定性,从而实现更高的累积转化数。本发明提供的制备R-香茅醛的方法,其中,反应底物在过渡金属催化剂存在下发生不对称氢化反应生成R-香茅醛,所述反应底物选自橙花醛和/或香叶醛,所述过渡金属催化剂为能溶于反应体系的过渡金属化合物与包含两个磷原子的光学活性配体反应而获得；将所述反应底物投入所述不对称氢化反应的反应体系之前,用硅铝酸盐和/或纳米银对所述反应底物进行预处理,并在预处理后过滤除去所述硅铝酸盐和/或纳米银。(The invention provides a method for preparing R-citronellal, which can remarkably improve the catalytic activity and stability of a catalyst based on the method, thereby realizing higher cumulative conversion number. The invention provides a method for preparing R-citronellal, wherein a reaction substrate is subjected to asymmetric hydrogenation reaction in the presence of a transition metal catalyst to generate the R-citronellal, the reaction substrate is selected from neral and/or geranial, and the transition metal catalyst is obtained by reacting a transition metal compound which can be dissolved in a reaction system with an optically active ligand containing two phosphorus atoms; before the reaction substrate is put into the reaction system of the asymmetric hydrogenation reaction, the reaction substrate is pretreated by aluminosilicate and/or nano silver, and the aluminosilicate and/or nano silver is removed by filtration after pretreatment.)

1. A process for preparing R-citronellal, wherein a reaction substrate selected from neral of formula (I) and/or geranial of formula (II) is subjected to asymmetric hydrogenation in the presence of a transition metal catalyst to produce R-citronellal of formula (III), wherein the transition metal catalyst is obtained by reacting a transition metal compound soluble in the reaction system with an optically active ligand containing two phosphorus atoms; characterized in that before the reaction substrate is put into the reaction system of the asymmetric hydrogenation reaction, the reaction substrate is pretreated by aluminosilicate and/or nano silver, and the aluminosilicate and/or nano silver is removed by filtration after the pretreatment;

2. the method according to claim 1, wherein the pretreatment is to stir the reaction substrate and aluminosilicate and/or nano silver at 10-60 ℃ for 0.5-24 hours.

3. The method according to claim 1 or 2, wherein the aluminosilicate is used in an amount of 0.01 to 1% by mass of the reaction substrate, and the nanosilver is used in an amount of 0.01 to 1% by mass of the reaction substrate.

4. A process according to any one of claims 1 to 3, wherein the aluminosilicate is selected from one or more of zeolite, bentonite, kaolin and montmorillonite, preferably montmorillonite, more preferably montmorillonite K10.

5. The method as claimed in any one of claims 1 to 4, wherein the nanosilver is selected from one or more nanosilver having a particle size of 20-40 nm, 40-60 nm, 60-120 nm or 120-150 nm, preferably from 60-120 nm.

6. The process according to any one of claims 1 to 5, wherein the transition metal element in the transition metal compound is selected from the group consisting of metal elements of group VIII of the periodic Table of the elements, preferably rhodium;

the transition metal compound is one or more of transition metal halide, transition metal carbonate and transition metal complex;

preferably, the transition metal complex is selected from complexes formed by coordination of transition metals and one or more of carbonyl compounds, acetylacetone compounds, hydroxyl compounds, cyclooctadiene, norbornadiene, cyclooctene, methoxy compounds, acetyl compounds, aliphatic carboxylic acid compounds or aromatic carboxylic acid compounds;

further preferably, the transition metal compound is selected from the group consisting of a transition metal halide, a complex in which a transition metal is coordinated to a carbonyl compound, a complex in which a transition metal is coordinated to cyclooctadiene, a complex in which a transition metal is coordinated to an acetyl compoundOne or more of the formed complexes; more preferably, the transition metal compound is selected from RhCl₃、Rh(OAc)₃、Rh(cod)₂BF₄、[Rh(cod)Cl]₂、Rh(CO)₂acac、[Rh(cod)OH]₂、[Rh(cod)OMe]₂、Rh₄(CO)₁₂And Rh₆(CO)₁₆Wherein "acac" is an acetylacetone ligand and "cod" is a cyclooctadiene ligand.

7. The method according to any one of claims 1 to 6, wherein the optically active ligand comprising two phosphorus atoms is selected from one or more of the following ligands of formula (IV), formula (V) and formula (VI):

wherein R is¹、R²Each independently of the others, an unbranched alkyl radical having from 1 to 20 carbon atoms, a branched alkyl radical OR a cyclic alkyl radical, optionally bearing one OR more olefinic double bonds, and/OR, optionally, one OR more identical OR different radicals from the group OR⁹、NR¹⁰R¹¹Halogen, C₆-C₁₀Aryl and C₃-C₉A substituent of heteroaryl; or R¹And R²Taken together to form a ring having from 4 to 20 ring-forming carbon atoms, and

R³、R⁴each independently hydrogen or straight chain C₁-C₄Alkyl or branched C₁-C₄Alkyl, and

R⁵、R⁶、R⁷、R⁸each independently is C₆-C₁₀Aryl, and each may optionally bear one or more substituents selected from C₁-C₄Alkyl radical, C₆-C₁₀Aryl radical, C₁-C₄Substituents of alkoxy and amino, and

R⁹、R¹⁰、R¹¹each independently is hydrogen, C₁-C₄Alkyl radical, C₆-C₁₀Aryl radical, C₇-C₁₂Aralkyl or C₇-C₁₂Alkylaryl, or R¹⁰、R¹¹Taken together to form an alkylene chain having 2 to 5 carbon atoms and optionally interrupted by an N atom or an O atom.

8. The method according to any one of claims 1 to 7, wherein the molar ratio of the transition metal atom in the transition metal compound to the optically active ligand comprising two phosphorus atoms is (0.5 to 10): 1, preferably (0.5-1): 1.

9. the process according to any one of claims 1 to 8, characterized in that the asymmetric hydrogenation is carried out at an absolute pressure of 1 to 100 bar, preferably 50 to 80 bar; the reaction temperature is from 0 to 120 ℃ and preferably from 25 to 90 ℃.

Technical Field

The invention relates to the technical field of preparation of R-citronellal, and particularly relates to a method for preparing R-citronellal by asymmetrically hydrogenating neral and/or geranial.

Background

Citronellal is a compound with a chiral center, and R-citronellal is an important intermediate for synthesizing L-menthol, so that the preparation method, particularly the low-cost and large-scale industrialized preparation method, has important significance.

Adv.synth.cat., 2003, 345 (1): 15-32 report a method for obtaining R-citronellal from myrcene by a Gaosha company through three-step reaction, wherein the core process is asymmetric isomerization of allylamine, and the process has long steps and needs to use a large amount of lithium reagent.

EP 0000315 reports a process for preparing optically active R-citronellal by hydrogenating geranial or neral in the presence of a catalyst complex which is soluble in the reaction system and consists of rhodium and a chiral phosphine, which process is not very chemoselective and stereoselective and uses a large amount of catalyst.

CN102458659 and CN103249484 adopt metal powder of 8 th group to 10 th group or supported metal catalyst, such as palladium carbon, palladium alumina and the like, under the concerted catalysis of chiral cyclic amine and acid, realize the asymmetric hydrogenation of citral to obtain chiral citronellal, and the preparation of the catalyst is difficult.

CN 101039894 discloses the homogeneous catalytic hydrogenation of neral to prepare optically active R-citronellal by using a complex of rhodium carbonyl and chiral phosphine, the catalyst is firstly subjected to CO and H₂The mixture is prefabricated and reacted in H mixed with small amount of CO₂Is carried out in (1). The catalyst can effectively improve the chemical and stereoselectivity of the product, but has the defect of low hydrogenation efficiency, and particularly has the defects of obviously reduced catalyst conversion frequency under the condition of high substrate/catalyst, repeated cyclic application of the catalyst, complex process operation, short service life of the catalyst, easy occurrence of noble metal coupling inactivation and the like.

In summary, although there are many reports on the asymmetric reduction of citral to obtain R-citronellal at present, most of the reports have the disadvantages of low hydrogenation efficiency and large catalyst usage, and particularly under the condition of high substrate/catalyst, the reaction rate is obviously reduced; after the reaction is finished, the catalyst can not be recycled, or the recycling and reusing conditions are harsh and the process is complex, so the economic cost is higher and the benefit is poor.

Therefore, a preparation method for preparing R-citronellal by asymmetrically hydrogenating geranial and/or neral is needed to be found, the activity of the catalyst is improved, and high accumulative conversion number is realized, so that the cost of the catalyst is reduced, and better economic benefit is brought.

Disclosure of Invention

In view of the above, the present invention provides a method for preparing R-citronellal by asymmetrically hydrogenating neral and/or geranial.

The inventor of the application surprisingly finds that the catalytic activity and stability of the catalyst can be remarkably improved, and a higher cumulative conversion number can be realized by pretreating reaction substrate raw materials, namely neral and/or geranial, by using aluminosilicate and/or nano silver in advance and then carrying out asymmetric hydrogenation on a homogeneous transition metal catalyst prepared from a transition metal compound and an optically active ligand containing two phosphorus atoms to prepare the R-citronellal.

In order to achieve the purpose, the invention provides the following technical scheme:

the invention provides a method for preparing R-citronellal, wherein a reaction substrate is subjected to asymmetric hydrogenation reaction in the presence of a transition metal catalyst to generate the R-citronellal shown in the following formula (III), the reaction substrate is selected from neral shown in the formula (I) and/or geranial shown in the formula (II), and the transition metal catalyst is obtained by reacting a transition metal compound which can be dissolved in a reaction system with an optically active ligand containing two phosphorus atoms; before the reaction substrate is put into a reaction system of the asymmetric hydrogenation reaction, pretreating the reaction substrate by using aluminosilicate and/or nano silver, and filtering to remove the aluminosilicate and/or nano silver after pretreatment;

in some embodiments, the pretreatment is to stir the reaction substrate and aluminosilicate and/or nano silver at 10-60 ℃ for 0.5-24 hours. The filtration method for removing aluminosilicate and/or nanosilver by filtration after pretreatment is not particularly limited, and for example, filtration under normal pressure, filtration under reduced pressure, centrifugal filtration and the like can be used.

In some embodiments, the aluminosilicate is present in an amount of 0.01% to 1% (e.g., 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.5%, 0.7%, 1%, etc.) of the mass of the reaction substrate and the nanosilver is present in an amount of 0.01% to 1% (e.g., 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.5%, 0.7%, 1%, etc.) of the mass of the reaction substrate.

In some embodiments, the aluminosilicate is selected from one or more of zeolite, bentonite, kaolin and montmorillonite, preferably montmorillonite, more preferably montmorillonite K10.

In some embodiments, the nano silver is selected from one or more of nano silver with the particle size of 20-40 nm, 40-60 nm, 60-120 nm or 120-150 nm, preferably nano silver with the particle size of 60-120 nm, and the inventors find that the nano silver with the preferred particle size has better selective adsorption effect on impurities in the reaction substrate raw material.

In the present invention, the reaction substrate may be neral or geranial or a mixture of neral and geranial, and for the mixture of neral and geranial, the ratio conventionally used in the art for preparing R-citronellal may be used. Preferred reaction substrates are neral reaction substrates having a neral/geranial molar ratio of at least 90:10, or geranial reaction substrates having a geranial/neral molar ratio of at least 90: 10. As is well known in the art, the optical purity of the obtained active citronellal depends on the ratio of neral to geranial in the raw material, the type and purity of the chiral ligand, and the optical purity of the prepared active citronellal is preferably at least 70ee percent.

The invention relates to an improvement on the method for producing R-citronellal by asymmetrically hydrogenating neral and/or geranial in the presence of at least one transition metal catalyst which is obtained by reacting a transition metal compound soluble in the reaction mixture with an optically active ligand containing two phosphorus atoms. By the improvement of the invention, the catalytic activity and stability of the catalyst can be obviously improved, thereby realizing higher cumulative conversion number.

In the present invention, the transition metal compound is a compound soluble in the reaction system of the asymmetric hydrogenation, that is, a reactant of the asymmetric hydrogenation. The transition metal compound used may employ those conventionally used in the art for preparing R-citronellal.

In some embodiments, the transition metal element in the transition metal compound is selected from the group consisting of metal elements of group VIII of the periodic table of the elements, preferably rhodium;

the transition metal compound may be one or more of a transition metal halide, a transition metal carbonate, and a transition metal complex.

In some embodiments, the transition metal complex is selected from complexes formed by coordination of a transition metal with one or more of a carbonyl compound, an acetylacetone compound, a hydroxyl compound, cyclooctadiene, norbornadiene, cyclooctene, a methoxy compound, an acetyl compound, an aliphatic carboxylic acid compound, or an aromatic carboxylic acid compound.

In some embodiments, the transition metal compound is selected from one or more of a transition metal halide, a complex of a transition metal coordinated to a carbonyl compound, a complex of a transition metal coordinated to cyclooctadiene, and a complex of a transition metal coordinated to an acetyl compound. Preferred transition metal compounds in the process of the invention are Rh (I) and Rh (III) and Rh (0) compounds. Preference is given to those transition metal compounds which already have at least one CO ligand. In some embodiments, preferably, the transition metal compound is selected from, for example, RhCl₃、Rh(OAc)₃、Rh(cod)₂BF₄、[Rh(cod)Cl]₂、Rh(CO)₂acac、[Rh(cod)OH]₂、[Rh(cod)OMe]₂、Rh₄(CO)₁₂And Rh₆(CO)₁₆Wherein "acac" is an acetylacetone ligand and "cod" is a cyclooctadiene ligand.

The specific choice of the transition metal compounds and complexes (optically active ligands comprising two phosphorus atoms) may be those known in the art and well described in the literature or may be prepared by the person skilled in the art analogously to compounds known in the art.

The optically active ligand containing two phosphorus atoms may employ those conventionally used in the art for preparing R-citronellal.

In some embodiments, the optically active ligand comprising two phosphorus atoms of the present invention is selected from one or more of the following ligands of formula (IV), formula (V) and formula (VI):

wherein R is¹、R²Each independently of the others, an unbranched alkyl group, a branched alkyl group OR a cyclic alkyl group having from 1 to 20 carbon atoms and optionally bearing one OR more (e.g. from 1 to 4) olefinic double bonds, and/OR, optionally, one OR more (e.g. from 1 to 4) identical OR different groups selected from OR⁹、NR¹⁰R¹¹Halogen, C₆-C₁₀Aryl and C₃-C₉A substituent of heteroaryl; or R¹And R²Taken together to form a 4-20 membered ring (i.e., having from 4 to 20 ring carbon atoms), and

R³、R⁴each independently hydrogen or straight chain C₁-C₄Alkyl or branched C₁-C₄Alkyl, and

R⁵、R⁶、R⁷、R⁸each independently is C₆-C₁₀Aryl, and each may optionally bear one or more (e.g. 1 to 8, preferably 1 to 4) substituents selected from C₁-C₄Alkyl radical, C₆-C₁₀Aryl radical, C₁-C₄Substituents of alkoxy and amino, and

R⁹、R¹⁰、R¹¹each independently is hydrogen, C₁-C₄Alkyl radical, C₆-C₁₀Aryl radical, C₇-C₁₂Aralkyl or C₇-C₁₂Alkylaryl, or R¹⁰、R¹¹Taken together to form an alkylene chain having 2 to 5 carbon atoms and optionally interrupted by an N atom or an O atom.

As an example, the optically active ligand containing two phosphorus atoms may employ one or more of a chiral bidentate diphosphine ligand having the following structural formula and enantiomers thereof:

wherein Ph denotes phenyl, Ph₂Refers to the two phenyl groups attached to P.

In the present invention, the molar ratio of the transition metal atom in the transition metal compound to the optically active ligand comprising two phosphorus atoms may be a molar ratio conventionally selected in the art, and is not particularly limited. In some embodiments, the molar ratio of the transition metal atom in the transition metal compound to the optically active ligand comprising two phosphorus atoms is (0.5-10): 1, preferably (0.5-1): 1.

in some embodiments, the asymmetric hydrogenation is carried out at a pressure of from 1 to 100 bar absolute, preferably from 50 to 80 bar absolute (that is, the hydrogen pressure); the reaction temperature is from 0 to 120 ℃ and preferably from 25 to 90 ℃. The reaction time is not particularly limited and may be determined by one skilled in the art according to the reaction conditions, and for example, the reaction time may be about 1h to about 150h, preferably about 2h to about 24 h.

The amount of the transition metal compound is not particularly limited, and those conventionally used in the art may be used, as appropriate by those skilled in the art according to the reaction requirements. For example, in some embodiments, the transition metal compound may be suitably used in an amount of 0.00001 mol% to 1 mol% based on the molar amount of the transition metal atom, based on the amount of the reaction substrate to be hydrogenated.

Based on the scheme of the invention, good optical purity and conversion rate of the product can be obtained, and in some preferred schemes, the optical purity of the product of asymmetric hydrogenation can reach more than 90ee percent, and the conversion rate can reach 99 percent.

Suitable reactors for carrying out the asymmetric hydrogenation of the invention are in principle all those vessels which allow reaction under the stated conditions, in particular pressure and temperature, and which are suitable for hydrogenation, for example autoclaves, tubular reactors, bubble columns, etc., without this being restricted in particular.

The process of the invention can be operated batchwise, semi-continuously or continuously and is particularly suitable for industrial scale production.

The technical scheme provided by the invention has the following beneficial effects:

the invention provides a method for preparing R-citronellal by pre-treating neral and/or geranial reaction substrates by aluminosilicate and/or nano-silver and then carrying out asymmetric hydrogenation on the pre-treated raw materials under the catalysis of a transition metal catalyst; the method can improve the activity of the catalyst, realize high substrate/catalyst ratio in a single reaction and have higher conversion number.

The commercially available artificially synthesized neral/geranial is mainly obtained by taking isoamylene alcohol and isoamylene aldehyde as raw materials to perform condensation reaction to generate corresponding acetal, and then performing cracking and rearrangement reaction, wherein small molecular impurities such as the isoamylene alcohol, the isoamylene aldehyde and the like can remain in the neral/geranial in the process. In a reaction system for preparing R-citronellal by carrying out asymmetric hydrogenation reaction on neral/geranial under the catalysis of a transition metal catalyst, the transition metal catalyst is easily poisoned by small molecular impurities in raw materials, so that the activity is rapidly reduced. The inventor of the application surprisingly discovers that the aluminosilicate is adopted to pretreat the raw material, and has strong adsorption performance on impurities in the raw material due to the fact that the aluminosilicate has a proper pore diameter and a large specific surface area, so that the accumulated poisoning effect of the impurities on the expensive transition metal catalyst is remarkably reduced, and the activity of the catalyst is remarkably improved. In addition, in a reaction system for preparing R-citronellal by carrying out asymmetric hydrogenation reaction on neral/geranial through catalysis of a transition metal catalyst, the transition metal catalyst is also easily poisoned by trace impurities containing heteroatoms such as sulfur, chlorine and the like in raw materials, and the inventor of the application also surprisingly discovers that the impurities containing the heteroatoms such as sulfur, chlorine and the like in the raw materials can be obviously reduced by adopting cheaper nano silver for pretreatment, so that the accumulated poisoning effect of the impurities on the expensive transition metal catalyst under high accumulated conversion number is reduced, the service life of the catalyst is obviously prolonged, the reusability of the homogeneous catalyst is facilitated, and the higher accumulated conversion number is realized. If aluminosilicate and nano silver are used for pretreating reaction substrates at the same time, better effect can be obtained.

Detailed Description

In order to better understand the technical solution of the present invention, the following examples are further provided to illustrate the present invention, but the present invention is not limited to the following examples.

Analytical instrument

Gas chromatograph: agilent7890, column DB-5 (conversion assay), column Supelco beta-DEX^TM225 (optical purity measurement), inlet temperature: 300 ℃; the split ratio is 50: 1; carrier gas flow: 52.8 ml/min; temperature rising procedure: at 95 ℃ for 40min, increasing to 180 ℃ at a rate of 10 ℃/min, for 40min, detector temperature: 280 ℃.

Optical purity:

optical purity ee% (% of R-citronellal peak area in gas chromatography-S-citronellal peak area in gas chromatography)/(R-citronellal peak area in gas chromatography + S-citronellal peak area in gas chromatography)

Conversion rate:

conversion rate 100% - (neral peak area in gas chromatogram + geranial peak area in gas chromatogram) × 100%/total peak area in gas chromatogram (solvent removal)

Turnover number:

the number of revolutions per mole of citronellal obtained by the reaction/mole of rhodium in the catalyst used

Reagent:

raw material (neral): 99% of carbofuran.

Starting material (geranial): 99% of carbofuran.

Rh(CO)₂acac、[Rh(cod)OH]₂、[Rh(cod)OMe]₂、Rh₄(CO)₁₂、Rh₆(CO)₁₆，98wt％，Aldrich；

A compound of formula (VII) -formula (XII) and isomers of the compound of formula (VII) (in particular, the compound of formula (VII) is (R, R) -chiralphos, the enantiomer thereof being (S, S) -chiralphos), 99 wt%, carbofuran.

Montmorillonite K10, montmorillonite KSF, montmorillonite PGW, montmorillonite PGV, montmorillonite PGN, and Nanocor;

zeolite, bentonite, kaolin, chemical purity, carbofuran;

20-40 nm, 40-60 nm, 60-120 nm, 120-150 nm of nano silver, Macklin.

The pressures referred to in the following examples are absolute pressures.