A method for synthesizing (s)-citronellal

Abstract

The application belongs to the field of fine chemical synthesis, and discloses a synthesis method of (S)-citronellal, which comprises the following steps: performing asymmetric hydrogenation reaction on citral in a hydrogen atmosphere under the action of an iron-based complex catalyst, and obtaining the (S)-citronellal after post-treatment after the reaction is completed. The synthesis method adopts a new catalyst system, and effectively improves the yield and selectivity of (S)-citronellal.

Description

Technical Field

[0001] This invention belongs to the field of fine chemical synthesis, specifically relating to a method for synthesizing (S)-citronellol. Background Technology

[0002] Citronellol, also known as 3,7-dimethyl-6-octenal, contains a chiral carbon atom in its molecule, thus exhibiting both R and S configurations. (S)-Citronellol is a colorless to pale yellow liquid with a strong lemon scent. It possesses strong antibacterial and insecticidal properties and is commonly used as a preservative and insect repellent. (S)-Citronellol is an important fragrance component with significant economic value.

[0003] In chemical synthesis, (S)-citronellol can be obtained through various routes, including extraction from natural citronella oil, chemical synthesis, and microbial fermentation. Currently, the main supplier in the market is Takasago of Japan, but no patent reports have been found for its industrial synthesis method.

[0004] BASF has a patent published in US20080280337A1 that uses prokaryotic strains to bioconvert citral into citronellol. In this patent, (S)-citronellol with an ee value greater than 99% is obtained using motile fermentation monocytogenes, but the yield is not given.

[0005] NHU's patent CN115739187B discloses the use of a supported iron-based catalyst to directly catalyze the asymmetric synthesis of (R)-citronellol from citral, achieving high conversion and selectivity. However, this method mainly yields (R)-citronellol and cannot produce (S)-citronellol.

[0006] The preparation of (S)-citronellol using chiral selective hydrogenation of citral is a more economical and convenient method. However, the optical rotation of (S)-citronellol is a challenge and a key issue in this method. Solving this problem is crucial for the large-scale industrial production of (S)-citronellol. Summary of the Invention

[0007] In response to the shortcomings of the existing technology, the inventors conducted further research to explore the highly selective asymmetric hydrogenation of citral to obtain (S)-citronellol.

[0008] This invention provides a method for synthesizing (S)-citronellol, comprising the following steps:

[0009] Under the action of an iron-based complexing catalyst, citral undergoes an asymmetric hydrogenation reaction in a hydrogen atmosphere, and after the reaction is completed, it is post-treated to obtain (S)-citronellol.

[0010] In this invention, the iron-based complex catalyst is prepared in situ using the following method:

[0011] The iron-based complex catalyst is obtained by mixing an iron source, an auxiliary metal salt, and a chiral ligand, and then heating the mixture under the protection of a carbon monoxide and hydrogen gas mixture (1:0.9~1.1 volume / volume, preferably 1:1 volume / volume).

[0012] The iron source is any one or a combination of iron-containing chlorides, nitrates, sulfates, acetylacetone salts or their hydrates; more preferably any one or a combination of FeCl3·6H2O, FeSO4·7H2O, Fe(NO3)3·9H2O, Fe(acac)3.

[0013] The auxiliary metal salt is selected from any one or a combination of chlorides, nitrates, sulfates, acetylacetone salts or hydrates of the auxiliary metal, or a phosphine-containing ligand complex of the auxiliary metal, wherein the auxiliary metal is one or more of Ru, Pd, and Rh.

[0014] The chiral ligand is selected from one or two of (+)-1,2-bis((2S,5S)-2,5-diphenylphosphine)ethane (CAS: 824395-67-7), (S)-(−)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and (R,R)-1,2-bis[(2-methoxyphenyl)(phenylphosphino)]ethane (CAS: 55739-58-7).

[0015] The molar ratio of the iron element to the auxiliary metal element is 1:0.1~0.5, preferably 1:0.1~0.3.

[0016] The molar ratio of iron to the chiral ligand is 1:1.1~2.0; preferably 1:1.1~1.3.

[0017] The catalyst is prepared at a temperature of 80~160℃; the mixed gas pressure is 2~4MPa; and the preparation time is 4~6 hours.

[0018] Preferably, the asymmetric hydrogenation reaction is carried out in a solvent, which is one or two of ethanol, methanol, toluene, acetone, and isopropanol.

[0019] The mass ratio of citral to solvent is 1:1 to 3, preferably 1:1.5 to 1.8.

[0020] The mass ratio of citral to the iron-based complex catalyst (based on the mass of iron) is 1:0.005~0.1, preferably 1:0.005~0.07.

[0021] The reaction temperature is 60–150°C, and the preferred reaction temperature is 80–100°C;

[0022] The hydrogen pressure for the asymmetric hydrogenation reaction is 2.0–7.0 MPa, preferably 3.0–5.0 MPa.

[0023] The reaction time is 2 to 6 hours.

[0024] Preferably, the post-processing procedure is as follows:

[0025] Solvent and unreacted raw materials are recovered under reduced pressure, and the reaction liquid is distilled using a 1-2m high-efficiency packed column with an absolute pressure of 30-80Pa at the top of the column. The fraction with a top temperature of 30-40℃ is collected to obtain (S)-citronellol product with qualified aroma.

[0026] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0027] This invention provides a method for synthesizing (S)-citronellol, which uses an iron-based complexing catalyst containing chiral ligands and performs an asymmetric hydrogenation reaction, thereby improving the reaction yield. This invention uses an inexpensive metal instead of the expensive metal rhodium, which significantly reduces production costs and is conducive to the large-scale industrial production of (S)-citronellol. Attached Figure Description

[0028] Figure 1 Here are the gas phase spectra and data of the product obtained in Example 3;

[0029] Figure 2 The mass spectrum of the product obtained in Example 3 (top image) is compared with that of the standard spectral library (bottom image);

[0030] Figure 3 The image shows the chiral spectrum of the product obtained in Example 3. Detailed Implementation

[0031] Unless otherwise defined, the technical terms used in the following embodiments have the same meanings as commonly understood by those skilled in the art. Unless otherwise specified, the experimental reagents used in the following embodiments are conventional biochemical reagents; and the experimental methods described are conventional methods.

[0032] S-citronellol gas chromatography detection conditions:

[0033] Chromatographic column: DB-FFAP, 30m*0.25mm*0.25µm. Detection instrument: Fuli 9790plus.

[0034] Temperature conditions: column oven 80℃, ramped up to 240℃ at 4℃ / min and held for 10min; injection port: 250℃; detector: 250℃.

[0035] Injection volume: 0.2 µl. Column inlet pressure: 0.10 MPa. Split ratio: 1 / 60. Carrier gas: High-purity nitrogen.

[0036] S-citronellol chiral detection method:

[0037] Chromatographic column: DM-DEX DAC Beta 25m×0.25mm×0.25µm. Detection instrument: Fuli 9790plus.

[0038] Hold at 60℃ for 10 min, then increase to 220℃ at a rate of 4℃ / min and hold for 10 min. Detector: 250℃, Inlet: 250℃.

[0039] Column flow rate: 0.8 mL / min

[0040] Flow split ratio: 80:1

[0041] Examples 1-25 and Comparative Examples 1-3

[0042] (1) In-situ synthesis of catalyst

[0043] Add 100g of iron salt, auxiliary metal salt, chiral ligand, and ethanol to a high-pressure reactor. After sealing, replace the high-pressure reactor three times with a mixture of carbon monoxide and hydrogen (1:1 volume / volume). Start stirring and raise the temperature to 80~160℃ (see Table 1 for details). The pressure of carbon monoxide and hydrogen (1:1 volume / volume) is 2MPa. Keep stirring at this temperature for 5 hours.

[0044] (2) Asymmetric hydrogenation

[0045] Cool and depressurize, add 100g of citral to the reactor, seal it, replace the reactor with hydrogen three times, adjust the hydrogen pressure to 2.0-7.0MPa, raise the temperature to 60-150℃, and react for 2-6 hours (see Table 1 for details). Use gas chromatography to detect the reaction solution and analyze the reaction results, see Table 1 for details.

[0046] After the reaction was completed, the mixture was filtered, and the solvent and unreacted raw materials were recovered from the filtrate under reduced pressure. The reaction liquid was then distilled using a 1m high-efficiency packed column with an absolute pressure of 30-80 Pa at the top. The fraction with a top temperature of 30-40℃ was collected to obtain the (S)-citronellol product. The gas phase spectrum of the product obtained in Example 3 is shown below. Figure 1 The mass spectrum of the finished product (top image) and the standard spectrum (bottom image) are shown below. Figure 2 The chiral spectrum of the finished product is shown below. Figure 3 .

[0047] Table 1

[0048]

[0049]

[0050] a Selectivity of total citronellol;

[0051] b Content of (S)-citronellol in total citronellol;

[0052] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A method for synthesizing (S)-citronellol, characterized in that, Includes the following steps: Under the action of an iron-based complexing catalyst, citral undergoes an asymmetric hydrogenation reaction in a hydrogen atmosphere, and after the reaction is completed, it is post-treated to obtain the (S)-citronellol. The iron-based complex catalyst was prepared in situ using the following method: The iron-based complex catalyst is obtained by mixing an iron source, an auxiliary metal salt, and a chiral ligand and then heating the mixture under the protection of a mixture of carbon monoxide and hydrogen. The volume ratio of carbon monoxide to hydrogen is 1:0.9~1.

1.

2. The method for synthesizing (S)-citronellol according to claim 1, characterized in that, The iron source is any one or a combination of iron-containing chlorides, nitrates, sulfates, acetylacetone salts or their hydrates.

3. The method for synthesizing (S)-citronellol according to claim 1, characterized in that, The auxiliary metal salt is selected from any one or a combination of chlorides, nitrates, sulfates, acetylacetone salts or hydrates of the auxiliary metal, or a phosphine-containing ligand complex of the auxiliary metal, wherein the auxiliary metal is one or more of Ru, Pd, and Rh.

4. The method for synthesizing (S)-citronellol according to claim 1, characterized in that, The chiral ligand is selected from one or two of (+)-1,2-bis((2S,5S)-2,5-diphenylphosphine)ethane, (S)-(−)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, and (R,R)-1,2-bis[(2-methoxyphenyl)(phenylphosphino)]ethane.

5. The method for synthesizing (S)-citronellol according to claim 1, characterized in that, The molar ratio of the iron element to the auxiliary metal element is 1:0.1~0.5; The molar ratio of the iron element to the chiral ligand is 1:1.1~2.

0.

6. The method for synthesizing (S)-citronellol according to claim 1, characterized in that, The catalyst is prepared at a temperature of 80~160℃; the mixed gas pressure is 2~4MPa; and the preparation time is 4~6 hours.

7. The method for synthesizing (S)-citronellol according to any one of claims 1 to 6, characterized in that, The asymmetric hydrogenation reaction is carried out in a solvent, which is one or two of ethanol, methanol, toluene, acetone, and isopropanol.

8. The method for synthesizing (S)-citronellol according to claim 7, characterized in that, The mass ratio of citral to solvent is 1:1~3; The mass ratio of citral to the iron-based complex catalyst is 1:0.005~0.1, based on the mass of iron.

9. The method for synthesizing (S)-citronellol according to any one of claims 1 to 6, characterized in that, The asymmetric hydrogenation reaction is carried out at a temperature of 60–150°C, with a hydrogen pressure of 2.0–7.0 MPa and a reaction time of 2–6 hours.

10. The method for synthesizing (S)-citronellol according to any one of claims 1 to 6, characterized in that, The post-processing procedure is as follows: Solvent and unreacted raw materials are recovered under reduced pressure, and the reaction liquid is distilled using a 1-2m high-efficiency packed column with an absolute pressure of 30-80 Pa at the top of the column. The fraction with a top temperature of 30-40℃ is collected to obtain (S)-citronellol product with qualified aroma.

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