Method for preparing optically active citronellal

Abstract

The invention provides a method for preparing optically active citronellal, which comprises the following steps: carrying out asymmetric hydrogenation on neral or geranial to prepare optically active R-citronellal, and a catalyst comprises transition metal rhodium, a diphosphine ligand and weakly alkaline anion exchange resin. According to the method, a certain amount of methane gas is introduced in the catalyst prefabrication process, the methane content is controlled to be 1000-3000 ppm of the total gas content, the catalytic stability of the asymmetric hydrogenation optically active transition metal catalyst for homogeneous catalysis is remarkably improved, R-citronellal with high optical purity is obtained, meanwhile, the catalyst application process is simplified, and the cost is reduced. And remarkable economic benefits are achieved.

Description

Technical Field

[0001] The present invention relates to a method for preparing optically active citronellal, and particularly to a method for asymmetric hydrogenation of neral or geranial to prepare optically active R-citronellal. Background Art

[0002] Citronellal, namely 3,7-dimethyl-6-octenal, contains a chiral carbon atom in its molecule, and thus has two configurations of R and S. Citronellal has a strong, fresh, green citrus-like and slightly woody aroma, and has a wide range of applications in food, spices and cosmetics. R-citronellal is an important spice ingredient, and it is also a precursor for synthesizing the important spice L-menthol.

[0003] CN103044204A and CN105541579A disclose a method for catalytic asymmetric hydrogenation of citral to synthesize R-citronellal using a dihydropyridine derivative as a hydride source and a chiral amine / chiral amine salt as a chiral auxiliary. However, due to the limitation of the hydrogen source, it is difficult to realize industrial production by this method.

[0004] CN110963902A discloses a method for aqueous-oil two-phase asymmetric hydrogenation synthesis of R-citronellal. This method makes the catalyst have good water solubility by using a water-soluble phosphine ligand, reacts in the aqueous-oil two-phase, and realizes the separation of the catalyst by phase separation after the reaction.

[0005] CN101675020A discloses a method for asymmetric hydrogenation of citral to prepare R-citronellal under homogeneous conditions. The catalyst is composed of a Rh center and a chiral P-containing ligand. The catalyst described in this method has poor stability, has high requirements for the reaction environment, requires at least one CO ligand on the catalyst, and the hydrogenation reaction needs to be carried out under the condition of the presence of external CO.

[0006] In summary, although there have been many reports on the asymmetric reduction of citral to obtain R-citronellal at present, most of these reports have the disadvantages of low hydrogenation efficiency and large catalyst dosage; after the reaction, the catalyst either cannot be recovered, or the conditions for recovery and reuse are harsh and the process is complex, so the economic cost is high and the efficiency is poor.

[0007] Therefore, it is necessary to find a preparation method for asymmetric hydrogenation of geranial or neral to R-citronellal to improve the activity and stability of the catalyst, thereby reducing the catalyst cost and bringing better economic benefits. Summary of the Invention

[0008] One object of the present invention is to provide an improved method for the asymmetric hydrogenation of geranial and / or neral to optically active citronellal. Surprisingly, it has been found that during the catalyst prefabrication process, in the presence of methane gas, a high turnover number of the catalyst can be achieved, thereby reducing the process risk and reducing the catalyst cost to an acceptable level for industrial-scale production.

[0009] In addition, by adding a weakly basic anion exchange resin to the catalyst, the cumulative poisoning effect of impurities in the raw materials on the catalyst can be significantly reduced, and the catalytic stability of the optically active transition metal catalyst for homogeneous catalytic asymmetric hydrogenation can be improved. On the one hand, the catalytic activity of the catalyst is significantly improved, and on the other hand, the service life of the catalyst is significantly increased.

[0010] In order to achieve the above object of the invention, the technical solution adopted by the present invention is as follows:

[0011] A method for preparing optically active citronellal, comprising the following steps: in the presence of a catalyst, asymmetrically hydrogenating neral of formula (I) or geranial of formula (II) to prepare optically active R-citronellal of formula (III), wherein the catalyst comprises rhodium with a catalytically active transition metal, a bisphosphine ligand, and a weakly basic anion exchange resin.

[0012]

[0013]

[0014] The rhodium in the present invention is derived from a compound of Rh(I), Rh(III) or Rh(0).

[0015] Further, the rhodium compound in the present invention comprises RhCl 3 , Rh(OAc) 3 , [Rh(cod)Cl] 2 , Rh(CO) 2 acac, [Rh(cod)OH] 2 , [Rh(cod)OMe] 2 , Rh 4 (CO) 12 , Rh 6 (CO) 16 or one or more of them, wherein "acac" is an acetylacetonate ligand and "cod" is a cyclooctadiene ligand. Preferably Rh(CO) 2 acac.

[0016] The molar ratio of the rhodium compound to the bisphosphine ligand in the catalyst of the present invention is 1:1.

[0017] As a preferred embodiment, the method for preparing optically active citronellal of the present invention comprises the following steps:

[0018] (1) Under an inert gas atmosphere, dissolve the rhodium compound, the diphosphine ligand and the weakly basic anion exchange resin in neral of formula (I) or geranial of formula (II) to obtain a mixed material containing the catalyst;

[0019] (2) Before carrying out the asymmetric hydrogenation reaction, introduce hydrogen gas and a certain content of methane gas. The methane content accounts for 1000 - 3000 ppm of the total gas. Under the condition that the total gas pressure is 0.5 - 4 MPa, stir the mixed material at 50 - 80 °C for 3 - 5 h, and then cool it to obtain a mixed material containing the pre-treated catalyst;

[0020] (3) Then place the mixed material containing the pre-treated catalyst under the reaction conditions required for the asymmetric hydrogenation reaction to carry out the reaction to obtain the optically active citronellal.

[0021] Further, the absolute pressure of the asymmetric hydrogenation is 0.5 - 5 MPa, preferably 1 - 4 MPa.

[0022] Further, the reaction temperature of the asymmetric hydrogenation is 40 - 100 °C, preferably 50 - 80 °C.

[0023] Further, the reaction time of the asymmetric hydrogenation is 5 - 8 h.

[0024] Further, the methane gas introduced during the prefabrication of the catalyst is between 1000 - 3000 ppm of the total gas volume.

[0025] Further, the pore diameter of the weakly basic anion exchange resin is 5 - 10 nm, and the specific surface area is 60 - 100 m² / g.

[0026] Further, the weakly basic anion exchange resin used is one or more of Purolite A100, Purolite A103SPlus, and Purolite A105, preferably Purolite A103 SPlus.

[0027] Further, the weakly basic anion exchange resin used is 0.01% - 0.1% of the mass of neral of formula (I) or geranial of formula (II).

[0028] Further, the rhodium as the catalytically active transition metal is derived from the rhodium compound. The molar ratio (S / C) of neral or geranial to the catalyst (calculated as rhodium) is greater than 5000:1, preferably S / C is (10,000 - 100,000):1.

[0029] Furthermore, the diphosphine ligand has optical activity and has the structural formula of formula (IV):

[0030]

[0031] Wherein,

[0032] R 1 and R 2 are each independently a hydrogen atom or an unbranched alkyl group, a branched alkyl group (specifically a branched alkyl group having 3 to 20 carbon atoms) or a cyclic alkyl group (specifically a cyclic alkyl group having 3 to 20 carbon atoms) having 1 to 20 carbon atoms, and may optionally carry one or more, for example, 1 to 4 ethylenic double bonds, and / or optionally carry one or more, for example, 1 to 4 substituents selected from the same or different halogens, C 6 -C 10 aryl and C 3 -C 9 heteroaryl; or R 1 and R 2 may together form one or more 4- to 20-membered rings, preferably the ring contains an unsaturated double bond and the ring-forming atoms on the ring are C atoms;

[0033] R 3 、R 4 、R 5 and R 6 are independently C 6 -C 10 aryl, and each optionally carries one or more, usually 1 to 8, preferably 1 to 4 substituents selected from C 1 -C 4 alkyl, C 6 -C 10 aryl, C 1 -C 4 alkoxy and amino.

[0034] As an example, the following compounds or their enantiomers are preferably used diphosphine ligands:

[0035]

[0036] Wherein Ph refers to a phenyl group, Ph 2 refers to two phenyl groups connected to P.

[0037] The catalyst can be recycled by methods known to those skilled in the art, for example, by distilling the resulting reaction product from the reaction mixture.

[0038] The reactors suitable for the asymmetric hydrogenation of the present invention are, in principle, all those containers that allow the reaction under the said conditions, especially pressure and temperature, and are suitable for the hydrogenation reaction, such as autoclaves, tubular reactors, bubble columns, etc.

[0039] The beneficial effects of the method of the present invention are as follows:

[0040] (1) During the use of the bisphosphine catalyst, it is easy to lose methyl groups. As shown in Reaction Formula 1, since the methyl group is an electron-donating group, it will increase the electron density of the phosphorus atom, which is beneficial to the improvement of the catalytic efficiency. However, during the reaction process, the bisphosphine catalyst loses methyl groups, resulting in a decrease in the electron density of the phosphorus atom, leading to a change in its valence band structure, thus affecting the stability of the catalyst. Therefore, adding methane to the reaction system plays a role in stabilizing the catalyst, significantly improving the catalytic stability of the optically active transition metal catalyst for homogeneous catalytic asymmetric hydrogenation, and thus achieving a higher turnover number.

[0041] (2) Since the weakly basic anion exchange resin, especially Purolite A103SPlus, has a suitable pore size and a large specific surface area, with a high degree of interception of macromolecules and a high selectivity for negative ions, macromolecular substances generated in the reaction system, trace nerol / geranial polymers in the raw material nerol / geranial, and impurities containing grafting groups such as sulfur and chlorine cannot pass through. Thus, substances that have an impact on the catalyst activity after accumulation during the recycling process are separated from the system, playing a very good purification role, and thereby ensuring the activity and stability of the recycled catalyst.

[0042] (3) Commercially available synthetic nerol / geranial is mostly obtained by the condensation reaction of isoprenol and isoprenaldehyde as raw materials under the action of an acidic catalyst to form the corresponding acetal, and then through a cracking reaction under the catalysis of an acidic catalyst, and the obtained product is obtained through a rearrangement reaction. As a result, trace acidic substances in nerol / geranial cannot be removed. The weakly basic anion exchange resin, especially Purolite A103SPlus, has a tertiary amine group and can react with trace acidic substances, significantly reducing the catalytic effect of the cis-trans isomerization reaction of nerol / geranial due to the presence of acidic impurities. Combining the above two remarkable points, the optical purity of the product R-citronellal is greatly improved. No new substances are generated, and the acid root ions are captured by the ammonium groups on the resin surface and will not affect the reaction.

[0043] Detailed implementation mode

[0044] The following further illustrates the method of the present invention through specific examples, but the present invention is not limited to the listed examples and should also include any other known changes within the scope of the claims of the present invention.

[0045] Analytical instruments

[0046] Gas chromatograph: Agilent 7890, chromatographic column DB-5, inlet temperature: 300 °C; split ratio 50:1; carrier gas flow rate: 50 ml / min; temperature programming: hold at 120 °C for 15 min, increase to 280 °C at a rate of 10 °C / min, hold for 10 min, detector temperature: 280 °C. This instrument is used to characterize the conversion rate of citral and the selectivity of citronellal.

[0047] Optical purity: Agilent 7890, chromatographic column β-dex-225, inlet temperature: 300 °C; split ratio 50:1; carrier gas flow rate: 50 ml / min; temperature programming: hold at 80 °C for 30 min, increase to 280 °C at a rate of 10 °C / min, hold for 10 min, detector temperature: 280 °C. This instrument is used to characterize the ee value of R-citronellal.

[0048] The ee value is the percentage of R-citronellal minus the percentage of S-citronellal, and the sum of the two is 100%.

[0049] Reagents:

[0050] Raw material (neral): 99%, Aladdin.

[0051] Raw material (geranial): 99%, Aladdin.

[0052] Rh(CO) 2 acac, [Rh(cod)OH] 2 , [Rh(cod)OMe] 2 Rh 4 (CO) 12 Rh 6 (CO) 16 , 98 wt%, Aldrich;

[0053] Compounds of formula (V) - formula (VIII) and isomers of the compound of formula (V) (the compound of formula (V) is specifically (R,R)-chiraphos, and its enantiomer is (S,S)-chiraphos): 99 wt%, Aladdin.

[0054] Purolite A103SPlus: Purolite Co., Ltd.

[0055] Example 1

[0056] Under a nitrogen atmosphere, 170.5 mg of Rh(CO) 20.66 mmol of acac and 283.8 mg of (R,R)-chiraphos (0.66 mmol) were dissolved in 1000 g of citral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 10,000:1. 10 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Methane was introduced to 0.1 bar (gauge pressure), and then hydrogen was introduced to 100 bar (gauge pressure), with the methane content being 1000 ppm of the total gas content. After stirring at 50 °C for 5 hours, the pressure was then released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 2 MPa by injecting hydrogen, and after heating to 60 °C and reacting for 6 h, the conversion rate of the substrate citral was 99.2%, the selectivity for citronellal was 99.5%, and the ee value was 89.1.

[0057] The results of catalyst reuse are shown in Table 1.

[0058] Table 1 Catalyst reuse in Example 1

[0059] Number of applications 5 10 15 20 25 30 Conversion rate / % 99.1 99.5 99.2 99.3 99.4 99.2 Selectivity / % 99.5 99.2 99.6 99.1 99.3 99.1 ee value 89.2 89.5 88.9 89.7 88.7 89.3

[0060] Example 2

[0061] Under a nitrogen atmosphere, 21.3 mg of Rh(CO) 2 0.083 mmol of acac and 35.5 mg of (R,R)-chiraphos (0.083 mmol) were dissolved in 1000 g of citral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 80,000:1. 50 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Methane was introduced to 0.2 bar (gauge pressure), and then hydrogen was introduced to 100 bar (gauge pressure), with the methane content being 2000 ppm of the total gas content. After stirring at 50 °C for 4 hours, the pressure was then released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 1 MPa by injecting hydrogen, and after heating to 80 °C and reacting for 8 h, the conversion rate of the substrate citral was 89.5%, the selectivity for citronellal was 99.2%, and the ee value was 88.9.

[0062] Example 3

[0063] Under a nitrogen atmosphere, 17.1 mg of Rh(CO) 2acac (0.066 mmol) and 28.4 mg (R,R)-chiraphos (0.066 mmol) were dissolved in 1000 g of citral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 100,000:1. 100 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Methane was introduced to 0.03 bar (gauge pressure), and then hydrogen was introduced to 100 bar (gauge pressure), with the methane content accounting for 3000 ppm of the total gas content. After stirring at 80 °C for 3 hours, then the pressure was released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 4 MPa by injecting hydrogen, and the temperature was raised to 50 °C and reacted for 5 h. The conversion rate of the substrate citral was 89.7%, the selectivity for citronellal was 99.1%, and the ee value was 89.6.

[0064] Example 4

[0065] Under a nitrogen atmosphere, 34.1 mg of Rh(CO) 2 acac (0.132 mmol) and 56.8 mg (R,R)-chiraphos (0.132 mmol) were dissolved in 1000 g of citral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 50,000:1. 50 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Methane was introduced to 0.16 bar (gauge pressure), and then hydrogen was introduced to 80 bar (gauge pressure), with the methane content accounting for 2000 ppm of the total gas content. After stirring at 50 °C for 5 hours, then the pressure was released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 3 MPa by injecting hydrogen, and the temperature was raised to 60 °C and reacted for 7 h. The conversion rate of the substrate citral was 99.5%, the selectivity for citronellal was 99.2%, and the ee value was 89.2.

[0066] Example 5

[0067] Under a nitrogen atmosphere, 34.1 mg of Rh(CO) 20.132 mmol of acac and 56.8 mg of (R,R)-chiraphos (0.132 mmol) were dissolved in 1000 g of neral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 50,000:1. 50 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Methane was introduced to 0.18 bar (gauge pressure), and then hydrogen was introduced to 90 bar (gauge pressure), with the methane content being 2000 ppm of the total gas content. After stirring at 70 °C for 4 hours, the pressure was then released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 2 MPa by injecting hydrogen, and after heating to 70 °C and reacting for 6 h, the conversion rate of the substrate neral was 99.4%, the selectivity for citronellal was 99.1%, and the ee value was 89.5.

[0068] Comparative Example 1

[0069] Under a nitrogen atmosphere, 34.1 mg of Rh(CO) 2 0.132 mmol of acac and 56.8 mg of (R,R)-chiraphos (0.132 mmol) were dissolved in 1000 g of neral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 50,000:1. It was transferred to an autoclave purged with methane. Methane was introduced to 0.18 bar (gauge pressure), and then hydrogen was introduced to 90 bar (gauge pressure), with the methane content being 2000 ppm of the total gas content. After stirring at 70 °C for 4 hours, the pressure was then released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 2 MPa by injecting hydrogen, and after heating to 70 °C and reacting for 6 h, the conversion rate of the substrate neral was 85.2%, the selectivity for citronellal was 86.5%, and the ee value was 78.2.

[0070] Comparative Example 2

[0071] Under a nitrogen atmosphere, 34.1 mg of Rh(CO) 2 0.132 mmol of acac and 56.8 mg of (R,R)-chiraphos (0.132 mmol) were dissolved in 1000 g of neral (6.60 mol) to obtain a solution, such that the S / C of the reaction was 50,000:1. 50 g of Purolite A103SPlus was added under stirring, and it was transferred to an autoclave purged with methane. Then hydrogen was introduced to 100 bar (gauge pressure), and after stirring at 70 °C for 4 hours, the pressure was then released to atmospheric pressure, and replaced with 0.5 Mpa of hydrogen. The reaction pressure was adjusted to 2 MPa by injecting hydrogen, and after heating to 70 °C and reacting for 6 h, the conversion rate of the substrate neral was 81.3%, the selectivity for citronellal was 82.9%, and the ee value was 75.6.

Claims

1. A method for preparing optically active citronellal, comprising the following steps: In the presence of a catalyst, asymmetric hydrogenation of neral of formula (I) or geranial of formula (II) is carried out to prepare optically active R-citronellal of formula (III), and the catalyst comprises catalytically active rhodium, a bisphosphine ligand and a weakly basic anion exchange resin, 2. The method according to claim 1, wherein, The rhodium is derived from a compound of Rh(I), Rh(III) or Rh(0); preferably, the rhodium is derived from RhCl 3 , Rh(OAc) 3 , [Rh(cod)Cl] 2 , Rh(CO) 2 acac, [Rh(cod)OH] 2 , [Rh(cod)OMe] 2 , Rh 4 (CO) 12 , Rh 6 (CO) 16 or one or more of them.

3. The method according to claim 1 or 2, wherein, The bisphosphine ligand has optical activity and the structural formula is formula (IV): wherein, R 1 and R 2 each independently is a hydrogen atom or an unbranched alkyl group having 1-20 carbon atoms, a branched alkyl group having 3-20 carbon atoms, a cyclic alkyl group having 3-20 carbon atoms, and may optionally carry 1 to 4 ethylenic double bonds, and / or optionally carry 1 to 4 substituents the same or different selected from halogen, C 6 -C 10 aryl and C 3 -C 9 heteroaryl; or R 1 and R 2 may together form one or more 4-20 membered rings, preferably the ring contains an unsaturated double bond and the ring-forming atoms on the ring are C atoms; R 3 , R 4 , R 5 and R 6 Independent of each other is C 6 -C 10 aryl, and each optionally carries 1-8, preferably 1-4, selected from C 1 -C 4 Alkyl, C 6 -C 10 Aryl, C 1 -C 4 Substituents of alkoxy and amino groups.

4. The method according to any one of claims 1-3, wherein, The bisphosphine ligand is selected from the following compounds or their enantiomers:

5. The method according to any one of claims 1-4, wherein, The pore size of the weakly basic anion exchange resin is 5-10 nm and the specific surface area is 60-100 m² / g.

6. The method according to any one of claims 1-5, wherein, The weakly basic anion exchange resin is one or more of Purolite A100, Purolite A103 SPlus, and Purolite A105.

7. The method according to any one of claims 1-6, wherein, The weakly basic anion exchange resin is 0.01% to 0.1% of the mass of neral of formula (I) or geranial of formula (II).

8. The method according to any one of claims 1-7, wherein, The molar ratio of neral or geranial to the catalyst (calculated as rhodium) is greater than 5000:1, preferably (10,000-100,000):

1.

9. The method according to any one of claims 1-8, wherein, The method for preparing optically active citronellal comprises the following steps: (1) Under an inert gas atmosphere, dissolve the rhodium compound, the bisphosphine ligand and the weakly basic anion exchange resin in neral of formula (I) or geranial of formula (II) to obtain a mixed material containing the catalyst; (2) Before carrying out the asymmetric hydrogenation reaction, introduce hydrogen gas and a certain content of methane gas, and stir the mixed material at 50-80 °C for 3-5 h under the condition that the total gas pressure is 0.5-4 MPa, and then cool to obtain a mixed material containing the pretreated catalyst; (3) Then place the mixed material containing the pretreated catalyst under the reaction conditions required for the asymmetric hydrogenation reaction to carry out the reaction to obtain the optically active citronellal.

10. The method according to claim 9, wherein, In the step (2), the methane content accounts for 1000-3000 ppm of the total gas.

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