Method for preparing chiral 2, 6-dimethyl-1-hydroxyindan through asymmetric hydrogenation and application of chiral 2, 6-dimethyl-1-hydroxyindan

Abstract

The invention discloses a method for preparing chiral 2, 6-dimethyl-1-hydroxyindan through asymmetric hydrogenation and an application of the chiral 2, 6-dimethyl-1-hydroxyindan in synthesis of a herbicide indaziflam. The method comprises the following steps: in the presence of a catalyst, alkali and a solvent, reducing 2, 6-dimethyl-1-indanone in a hydrogen atmosphere to obtain (1S, 2S)-2, 6-dimethyl-1-hydroxyindane; the catalyst includes a complex of [Ir (COD) Cl] 2 and a chiral ligand. The method provided by the invention has the advantages of less catalyst dosage, good reaction selectivity, short reaction time, mild conditions and easiness in industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of intermediates for herbicide indaziflam, in particular to a method for preparing chiral 2,6-dimethyl-1-hydroxyindane by asymmetric hydrogenation and application thereof. BACKGROUND

[0002] Indaziflam is a triazine herbicide developed by Bayer CropScience, which has novel chemical structure and good compounding performance, and can be used for controlling various grass weeds and broadleaf weeds. Compared with the previous triazine herbicide, indaziflam has more novel chemical structure and more excellent compounding performance, and can be used alone before seedling or in combination with other post-emergence herbicides for post-emergence weed control, thus having broad market prospect. (1S, 2S)-2,6-dimethyl-1-hydroxyindane (Formula I) is one of the key intermediates for synthesizing triazine indanofan (Formula II).

[0003]

[0004] It can be obviously found from the structural formula that the construction of two adjacent trans chiral carbons is the biggest difficulty in the synthesis of indaziflam.

[0005] In WO2004069814A1 and CN100448850C, Bayer CropScience first separates the cis and trans isomers by column chromatography, then separates the amine indane with (1S, 2R) configuration which is not needed by selective asymmetric esterification catalyzed by enzyme, and finally hydrolyzes the ester to separate the target (1R, 2S) amine indane structure. In this process, the final target product only accounts for 1 / 4 of the raw material, and the other configurations are basically wasted, which is a very uneconomical and inefficient method.

[0006]

[0007] It is reported in Tetrahedron 2007, 63(29), 6755-6763 that 2,6-dimethyl-1-indanone is used as raw material, asymmetric hydrogenation is carried out in the presence of chiral catalyst based on Rh or Ru to obtain (1S, 2S)-2,6-dimethyl-1-hydroxyindane, the configuration is reversed in DPPA-DBU to obtain the trans azide compound, and finally LiAlH4 is used for reduction to obtain (1R, 2S)-2,6-dimethyl-1-aminindane. However, the catalyst dosage is large, the substrate / catalyst ratio (S / C) is only 200:1, the reaction time is very long, which needs 7 days, the yield is 80%, the cis:trans ratio is 97:3, the enantiomeric ratio er cis =98:2, and it is difficult to realize industrialization.

[0008]

[0009] Shanghai Puyi Chemical Technology Co., Ltd. mentioned in Chinese patent CN108794339B that by palladium-catalyzed reduction reaction combined with non-chiral acid and 2, 6-dimethyl-1-hydroxy indane crystallization separation, first isolated trans-2, 6-dimethyl-1-hydroxy indane, and then through chiral resolution with R-mandelic acid, the final target compound (1R, 2S) aminoindeane was obtained. According to the patent technology, the first step uses non-chiral acid to separate cis and trans, which ensures the cis and trans ratio of 99:1, and the yield is only 30.2%. In the second step, when chiral mandelic acid is used to separate chiral target product, the er is ensured to be 99.8:0.2, and the single yield is 31.7%. If the yield is increased to 55%, the er is 90:10. Therefore, the resolution efficiency of this method is low, the amount of resolving agent is large, and it is not suitable for industrialization. SUMMARY

[0010] In view of the above technical problems and the deficiencies in the art, the present application provides a method for preparing chiral 2, 6-dimethyl-1-hydroxy indane by asymmetric hydrogenation and its application. The catalyst used in the method has less dosage, good reaction selectivity, short reaction time, mild conditions, and is easy to industrialize.

[0011] The specific technical solutions are as follows:

[0012] [1] A method for preparing chiral 2, 6-dimethyl-1-hydroxy indane by asymmetric hydrogenation, comprising:

[0013] (1S, 2S)-2, 6-dimethyl-1-hydroxy indane is obtained by reducing 2, 6-dimethyl-1-indanone in the presence of a catalyst, a base and a solvent under a hydrogen atmosphere;

[0014] The catalyst comprises a complex of [Ir(COD)Cl]2 and a chiral ligand; the chiral ligand comprises any one or more of the compounds having the structure shown below:

[0015]

[0016] Wherein:

[0017] R 1 is selected from cyclohexyl without substitution or with one or more substituents, phenyl without substitution or with one or more substituents, and the substituents on cyclohexyl and phenyl are independently selected from C1-C4 alkyl, such as methyl, tert-butyl, etc.; for example, R 1 may be selected from Ph, 4-MeC6H4, 3,5-Me2C6H3, 3,5-( t Bu)2C6H3, Cy, etc.

[0018] R 2 selected from H, C1-C6 alkyl (e.g. Me, R 3 selected from H, C1-C6 alkyl (e.g. Me, i Pr, t Bu, etc.), phenyl, benzyl.

[0019] For example, the chiral ligand can comprise any one or more of the compounds L1-L23 having the following structures:

[0020]

[0021]

[0022] The chiral ligands used in the present application are all known in the art and can be obtained commercially or prepared according to known procedures.

[0023] [1] The process for preparing chiral 2,6-dimethyl-1-hydroxyindan by asymmetric hydrogenation, the molar ratio of said [Ir(COD)Cl]2 and said chiral ligand can be 1:1-4, for example, it can be 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, etc.

[0024] [1] The process for preparing chiral 2,6-dimethyl-l-hydroxyindan by asymmetric hydrogenation, wherein the molar ratio of 2,6-dimethyl-l-indanone to Ir can be 5000-300000: 1, for example, it can be 6000: 1, 6500: 1, 7000: 1, 7500: 1, 8000: 1, 8500: 1, 9000: 1, 9500: 1, 10000: 1, 11000: 1, 12000: 1, 13000: 1, 14000: 1, 15000: 1, 16000: 1, 17000: 1, 18000: 1, 19000: 1, 20000: 1, 21000: 1, 22000: 1, 23000: 1, 24000: 1, 25000: 1, 26000: 1, 27000: 1, 28000: 1, 29000: 1, 30000: 1, 31000: 1, 32000: 1, 33000: 1, 34000: 1, 35000: 1, 36000: 1, 37000: 1, 38000: 1, 39000: 1, 40000: 1, 41000: 1, 42000: 1, 43000: 1, 44000: 1, 45000: 1, 46000: 1, 47000: 1, 48000: 1, 49000: 1, 50000: 1, 51000: 1, 52000: 1, 53000: 1, 54000: 1, 55000: 1, 56000: 1, 57000: 1, 58000: 1, 59000: 1, 60000: 1, 61000: 1, 62000: 1, 63000: 1, 64000: 1, 65000: 1, 66000: 1, 67000: 1, 68000: 1, 69000: 1, 70000: 1, 71000: 1, 72000: 1, 73000: 1, 74000: 1, 75000: 1, 76000: 1, 77000: 1, 78000: 1, 79000: 1, 80000: 1, 81000: 1, 82000: 1, 83000: 1, 84000: 1, 85000: 1, 86000: 1, 87000: 1, 88000: 1, 89000: 1, 90000: 1, 91000: 1, 92000: 1, 93000: 1, 94000: 1, 95000: 1, 96000: 1, 97000: 1, 98000: 1, 99000: 1, 100000: 1, 110000: 1, 120000: 1, 130000: 1, 140000: 1, 150000: 1, 160000: 1, 170000: 1, 180000: 1, 190000: 1, 200000: 1, 210000: 1, 220000: 1, 230000: 1, 240000: 1, 250000: 1, etc.The method of the present application can achieve high conversion efficiency and high selectivity with low catalyst usage ratio.

[0025] [1] The method of preparing chiral 2,6-dimethyl-1-hydroxyindan by asymmetric hydrogenation, the base can include at least one of an organic base, an inorganic base, for example, can include at least one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide.

[0026] [1] The method of preparing chiral 2,6-dimethyl-1-hydroxyindan by asymmetric hydrogenation, the molar ratio of the 2,6-dimethyl-1-indanone to the base can be 1000:1 to 10000, further can be 200:1 to 200, for example, can be 150:1, 140:1, 130:1, 120:1, 110:1, 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 25:1, 20:1, 15:1, 10:1, 5:1, 1:1, etc.

[0027] [1] The method of preparing chiral 2,6-dimethyl-1-hydroxyindan by asymmetric hydrogenation, the solvent can include at least one of toluene, isopropyl alcohol, dichloromethane, tetrahydrofuran, methanol, ethanol, trifluoroethanol, 1,2-dichloroethane, ethyl acetate, acetonitrile, 1,4-dioxane.

[0028] [1] The method for preparing chiral 2,6-dimethyl-l-hydroxyindan by asymmetric hydrogenation, the ratio of the amount of use of the 2,6-dimethyl-l-indanone to the solvent can be 1 mmol:0.1-10 mL, for example, can be 1 mmol:0.2 mL, 1 mmol:0.3 mL, 1 mmol:0.4 mL, 1 mmol:0.5 mL, 1 mmol:0.6 mL, 1 mmol:0.7 mL, 1 mmol:0.8 mL, 1 mmol:0.9 mL, 1 mmol:1.0 mL, 1 mmol:1.1 mL, 1 mmol:1.2 mL, 1 mmol:1.3 mL, 1 mmol:1.4 mL, 1 mmol:1.5 mL, 1 mmol:1.6 mL, 1 mmol:1.7 mL, 1 mmol:1.8 mL, 1 mmol:1.9 mL, 1 mmol:2.0 mL, 1 mmol:2.1 mL, 1 mmol:2.2 mL, 1 mmol:2.3 mL, 1 mmol:2.4 mL, 1 mmol:2.5 mL, 1 mmol:2.6 mL, 1 mmol:2.7 mL, 1 mmol:2.8 mL, 1 mmol:2.9 mL, 1 mmol:3.0 mL, 1 mmol:3.1 mL, 1 mmol:3.2 mL, 1 mmol:3.3 mL, 1 mmol:3.4 mL, 1 mmol:3.5 mL, 1 mmol:3.6 mL, 1 mmol:3.7 mL, 1 mmol:3.8 mL, 1 mmol:3.9 mL, 1 mmol:4.0 mL, 1 mmol:5.0 mL, 1 mmol:6.0 mL, 1 mmol:7.0 mL, 1 mmol:8.0 mL, 1 mmol:9.0 mL, etc.

[0029] [1] The method for preparing chiral 2,6-dimethyl-l-hydroxyindan by asymmetric hydrogenation, the pressure of the hydrogen gas can be 2-80 atm, for example, can be 10 atm, 15 atm, 20 atm, 25 atm, 30 atm, 35 atm, 40 atm, 45 atm, 50 atm, 55 atm, 60 atm, 65 atm, 70 atm, 75 atm, etc.

[0030] [1] The method for preparing chiral 2,6-dimethyl-l-hydroxyindan by asymmetric hydrogenation, the temperature of the reduction can be 0-50°C, for example, can be room temperature environment or 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, etc., and the time of the reduction can be 2-60 h, for example, can be 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 40 h, 50 h, etc.

[0031] In some embodiments, the method for preparing chiral 2,6-dimethyl-1-hydroxyindane by asymmetric hydrogenation according to [1] specifically comprises:

[0032] mixing [Ir(COD)Cl]2 and the chiral ligand in a solvent to obtain a complex solution;

[0033] mixing a base and a solvent to obtain a base solution;

[0034] mixing 2,6-dimethyl-1-indanone and a solvent to obtain a substrate solution;

[0035] mixing the complex solution, the base solution and the substrate solution and transferring them into a high-pressure resistant container, introducing hydrogen into the high-pressure resistant container to provide a hydrogen atmosphere, and performing a reduction reaction to obtain (1S,2S)-2,6-dimethyl-1-hydroxyindane.

[0036] [2] Application of the method for preparing chiral 2,6-dimethyl-1-hydroxyindane by asymmetric hydrogenation according to [1] in the synthesis of herbicide indaziflam.

[0037] Compared with the prior art, the present application has the following beneficial effects:

[0038] The present application has the advantages of simple operation, mild conditions, high conversion rate and selectivity, low cost, high atom economy, environmental friendliness and the like, and has a very good prospect of industrial application. DETAILED DESCRIPTION

[0039] The present application will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and not to limit the scope of the present application.

[0040] In the following examples, all reactions and operations sensitive to moisture or air were carried out in an argon-filled glove box or using Schlenk tubes, and [Ir(COD)Cl]2 was purchased from Aldrich.

[0041] Isopropanol was used as the solvent, sodium tert-butoxide was used as the base, and L8 was used as the chiral ligand. In an argon-filled glove box, a 10 mL vial was added with a metal precursor [Ir(COD)Cl]2 (1.4 mg, 2.0 x 10 -3 mmol), a ligand L8 (4.2 x 10 -3 mmol) and anhydrous isopropanol i-PrOH (2 mL), and the resulting mixture was stirred at 25℃ for 2 h. The solution (50 μL, c (Ir) = 2 x 10 -3 mmol / mL) and sodium tert-butoxide t-BuONa (0.01 mmol) in isopropanol i-PrOH (200 μL, c (t-BuONa)The solution (1S,2S) was transferred to a 5mL vial containing 2,6-dimethyl-1-indanone (1.0 mmol) in isopropanol i-PrOH (2 mL). The 5mL vial was then transferred to an autoclave, and 50 atm of H2 was introduced. The mixture was stirred at room temperature for 12 h. After the reaction was complete, hydrogen was slowly released in a well-ventilated fume hood. The product solution was concentrated and purified by column chromatography to obtain (1S,2S)-2,6-dimethyl-1-hydroxyindanone. The yield was 99%, the diastereomeric ratio (dr) was 95:5, and the enantiomeric excess percentage (ee) was 99% as determined by HPLC.

[0042] Following the above method, solvents were screened, and the types of solvents were changed while all other aspects remained the same. The results are shown in Table 1.

[0043] Table 1

[0044] Solvent Yield (%) ee (%) dr Methanol MeOH -- -- -- Ethanol EtOH 15 63 90:10 Isopropanol I-PrOH 99 99 95:5 1,2-Dichloroethane 13 70 70:30 Toluene 85 91 85:15

[0045] Following the above method, alkalis were screened, and the types of alkalis were changed while the rest remained the same. The results are shown in Table 2.

[0046] Table 2

[0047] Base Yield (%) ee (%) dr Sodium hydroxide 50 86 60:40 Sodium tert-butoxide 99 99 95:5 Potassium tert-butoxide 99 90 92:8 Potassium carbonate 20 83 50:50

[0048] Following the above method, ligands were screened, and the types of ligands were changed while the rest remained the same. The results are shown in Table 3.

[0049] Table 3

[0050] Ligand Yield (%) ee (%) dr L3 95 92 90:10 L7 99 96 92:8 L8 99 99 95:5 L16 70 87 80:20

[0051] Furthermore, it should be understood that after reading the above description of the present invention, those skilled in the art can make various alterations or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A process for the preparation of chiral 2,6-dimethyl-l-hydroxyindan by asymmetric hydrogenation, characterized in that, Comprising: reducing 2,6-dimethyl-1-indanone in the presence of a catalyst, a base, a solvent, under a hydrogen atmosphere to obtain (1S,2S)-2,6-dimethyl-1-indanol; the catalyst comprises a complex of [Ir(COD)Cl]2 and a chiral ligand; the chiral ligand comprises any one or more of the compounds having the structure shown below: wherein: R 1 is selected from the group consisting of unsubstituted or substituted with one or more substituents cyclohexyl, unsubstituted or substituted with one or more substituents phenyl, the substituents on cyclohexyl, phenyl are each independently selected from the group consisting of C1-C4 alkyl; R 2 selected from the group consisting of R 3 selected from the group consisting of H, C1-C6 alkyl, phenyl, benzyl.

2. The method of claim 1, wherein, the chiral ligand comprises any one or more of the compounds L1-L23 having the following structures:

3. The method according to claim 1 or 2, characterized in that, the molar ratio of the [Ir(COD)Cl]2 to the chiral ligand is 1:1-4.

4. The method of claim 1, wherein, the molar ratio of the 2,6-dimethyl-1-indanone to Ir is 5000-300000:

1.

5. The method of claim 1, wherein, the base comprises at least one of an organic base, an inorganic base, and further comprises at least one of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, potassium methoxide, sodium ethoxide, potassium carbonate, sodium carbonate, cesium carbonate, potassium hydroxide, sodium hydroxide.

6. The method according to claim 1 or 5, characterized in that, the molar ratio of the 2,6-dimethyl-1-indanone to the base is 1000:1-10000, and further can be 200:1-200.

7. The method of claim 1, wherein, the solvent comprises at least one of toluene, isopropanol, dichloromethane, tetrahydrofuran, methanol, ethanol, trifluoroethanol, 1,2-dichloroethane, ethyl acetate, acetonitrile, 1,4-dioxane; and / or, the amount ratio of the 2,6-dimethyl-1-indanone to the solvent is 1 mmol: 0.1-10 mL.

8. The method of claim 1, wherein, the pressure of the hydrogen is 2-80 atm.

9. The method of claim 1, wherein, the temperature of the reduction is 0-50°C, and the time of the reduction is 2-60 h.

10. Use of the method according to any one of claims 1-9 in the synthesis of the herbicide dimethenamid.

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