Preparation method of high-optical-purity (S)-indoxacarb intermediate

Abstract

The invention discloses a preparation method of a high-optical-purity (S)-indoxacarb intermediate, which comprises the following steps: reacting a compound # imgabs0 # as shown in the specification with a zirconium-containing compound in a solvent at a certain temperature by taking a structure shown in L1 as a chiral ligand to generate a chiral Zr-Salan complex solution system; and then adding 5-chloro-1-indanone-2-methyl formate (2) and an oxidizing agent into the solution, and carrying out an asymmetric hydroxylation reaction, so as to obtain the (S)-5-chloro-2, 3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (1). According to the method, the chiral Zr-Salan complex is used as the catalyst, and non-polar solvents such as petroleum ether are selected, so that a product with high photochemical purity can be efficiently generated in the reaction at room temperature without an anhydrous condition, the product can be purified only by filtration, and the catalytic system can be recycled for more than three times.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical catalysis, and in particular to a method for preparing a high optical purity (S)-indoxacarb intermediate, in particular to a method for preparing (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester. Background Art

[0002] Chiral pesticides have gradually become an important frontier field of new "high-efficiency and low-risk" green pesticide research due to their advantages such as high efficacy, small dosage and high safety. For example, oxadiazine insecticides are new insecticides with epoch-making significance discovered after pyrethroids, imidacloprid and other insecticides. Indoxacarb is a new type of oxadiazine-type highly efficient sodium ion channel blocking insecticide developed by DuPont in the United States. It can effectively control almost all lepidopteran pests. Under the premise of correct use, indoxacarb has high safety to non-target objects such as humans, animals, environment and crops. At the same time, indoxacarb has no cross-resistance with other types of insecticides such as pyrethroids and organophosphates. Therefore, indoxacarb is an ideal agent to replace highly toxic, highly residual and highly resistant insecticides, and has broad market and application prospects. Indoxacarb contains a chiral carbon atom in the molecule, with two chiral configurations, R and S. Since only the S chiral configuration has insecticidal activity, the content of indoxacarb products sold on the market is usually calculated as (S)-indoxacarb product. Therefore, the development of a method for the efficient synthesis of (S)-indoxacarb has important economic value and social benefits.

[0003]

[0004] At present, the key to the preparation of (S)-indoxacarb is to obtain its chiral intermediate (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (1). The existing technology mainly uses cinchona alkaloid derivatives, chiral Zr-Salan polymers, chiral Cu-Schiff base complexes, chiral guanidine derived from tartaric acid, (S)-timolol derivatives, etc. as chiral catalysts, and the asymmetric α-hydroxylation reaction of 5-chloro-1-indanone-2-carboxylic acid methyl ester (2) is the main method for preparing the chiral intermediate. However, these methods have the problems of harsh reaction conditions (for example, anhydrous conditions, low temperatures of -20 or -78°C or high temperatures of 80°C), cumbersome catalyst preparation processes (for example, the preparation of chiral Zr-Salen polymers, chiral guanidine derived from tartaric acid and S-timolol derivatives), and the need for column chromatography to separate products.

[0005]

[0006] For example, the prior art CN109701655A discloses a new catalyst and a method for preparing the S-body of indoxacarb using the catalyst. The catalyst is prepared from 3-tert-butyl-5-chloromethyl salicylaldehyde, cyclohexanediamine and zirconium acetylacetonate as raw materials, and the catalyst replaces the original cinchona alkali catalysts such as cinchona, and is applied to the asymmetric synthesis reaction of tert-butyl hydroperoxide and 5-chloro-2-methoxycarbonyl-1-indanone ester. Although the use of the above catalyst can increase the S-body content from 75% to 98%, its catalytic yield is only about 50%, and the preparation of the catalyst is relatively cumbersome, the reaction temperature needs to be high temperature, and the method for separating the product is more complicated.

[0007] Therefore, there is an urgent need to develop a method with simple catalyst preparation, mild reaction conditions, and no need for column chromatography to separate products to synthesize the (S)-indoxacarb intermediate (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester. Summary of the invention

[0008] In view of the deficiencies in the prior art, the present invention designs a method for preparing (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester, an intermediate of (S)-indoxacarb with high optical purity, which is suitable for industrial production.

[0009] One of the purposes of the present invention is to provide a method for preparing a high optical purity (S)-indoxacarb intermediate, characterized in that a chiral Zr-Salan complex solution system is used as a catalyst, petroleum ether is used as a solvent, a 70% aqueous solution of tert-butyl hydroperoxide is used as an oxidant, and 5-chloro-1-indanone-2-carboxylic acid methyl ester (Formula 2) is added to carry out an asymmetric hydroxylation reaction to obtain (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (Formula 1); the preparation method of the catalyst is: a chiral ligand L1 and a zirconium-containing compound react in a solvent at a certain temperature to generate a chiral Zr-Salan complex solution system;

[0010]

[0011] Furthermore, the molar ratio of the chiral ligand L1 to the zirconium-containing compound is 0.5:1.0-4.0:1.0, preferably 0.8:1.0-2.0:1.0.

[0012] Furthermore, the amount of the solvent used is 1 mL-100 mL per 0.1 mmol of the zirconium-containing compound, preferably 20 mL-50 mL per 0.1 mmol of the zirconium-containing compound.

[0013] Furthermore, the reaction temperature of the chiral ligand L1 and the zirconium-containing compound in a solvent to generate the chiral Zr-Salan complex is 0°C-60°C, preferably 20°C to 40°C. The asymmetric hydroxylation reaction temperature is 0°C to 60°C, preferably 20°C to 40°C.

[0014] Furthermore, the amount of the oxidant used is 20%-500% of the molar amount of 5-chloro-1-indanone-2-carboxylic acid methyl ester, preferably 100%-200%.

[0015] Furthermore, the amount of the chiral Zr-Salan complex used is 0.1%-100% of the molar amount of 5-chloro-1-indanone-2-carboxylic acid methyl ester, preferably 2%-10%.

[0016] Furthermore, the zirconium-containing compound is zirconium hydroxide, zirconium oxychloride, zirconium oxide, zirconium acetylacetonate, zirconium trifluoroacetylacetonate, zirconium n-propoxide, zirconium tert-butoxide, zirconium phosphate, zirconium bromide or a mixture thereof, preferably zirconium acetylacetonate or zirconium trifluoroacetylacetonate.

[0017] Further, the preparation method of the chiral ligand of the structure shown in L1 is as follows:

[0018]

[0019] The invention has the following beneficial effects: a chiral Zr-Salan complex is used as a catalyst, wherein a chiral Salan ligand can be efficiently synthesized in only two steps; by selecting non-polar solvents such as petroleum ether, the reaction can efficiently generate products with high photochemical purity at room temperature without anhydrous conditions; at the same time, since anhydrous conditions are not required, the reaction can use a more environmentally friendly and economical tert-butyl hydroperoxide aqueous solution as an oxidant; in addition, by utilizing the characteristics that the product has low solubility in the non-polar solvent while the raw materials and the catalyst have high solubility therein, the product can be purified by filtering without column chromatography, and the catalytic system can be recycled three times, and the number of cycles of the catalytic system can be adjusted according to the optical purity requirements of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 is the chiral ligand L1 of the present invention 1 H-NMR spectrum;

[0021] Figure 2 The (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester of the present invention 1 H-NMR spectrum;

[0022] Figure 3 is a liquid chromatogram of the racemic form of 5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester of the present invention;

[0023] Figure 4 A liquid chromatogram of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester used once for the catalyst system of the present invention;

[0024] Figure 5 The liquid chromatogram of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester used twice for the catalyst system of the present invention;

[0025] Figure 6 Liquid chromatogram of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester used three times for the catalyst system of the present invention. DETAILED DESCRIPTION

[0026] The following is further described in detail through specific implementation methods:

[0027] The reference numerals in the drawings of the specification include:

[0028] Example 1. Preparation of chiral ligand L1

[0029] The reaction formula is as follows

[0030]

[0031] Compound 3 (2.010 g, 10 mmol), compound 4 (1.823 g, 12 mmol), Pd(PPh3)4 (0.254 g, 0.22 mmol), K2CO3 (3.040 g, 22 mmol), toluene (60 mL) and ethanol (15 mL) were added to a reaction bottle, and then heated to reflux under argon protection. After the reaction was completed by TLC detection, diatomaceous earth was filtered, and the filtrate was spin-dried and silica gel column chromatography was performed to obtain compound 5 (2.043 g, 89%).

[0032] Compound 5 (1.826 g, 8 mmol), (1S, 2S)-1,2-diphenylethylenediamine (0.849 g, 4.0 mmol) and ethanol (120 mL) were added to a reaction flask, and then heated to reflux under argon protection. After 14 hours, the reaction was cooled to room temperature, and sodium borohydride (0.454 g, 12 mmol) was slowly added thereto in batches. After the addition, the reaction was allowed to react at room temperature. After 5 hours, sodium borohydride (0.227 g, 6 mmol) was added to the above reaction solution. After 1 hour, the above solution was poured into water (50 mL), and then the ethanol was removed under reduced pressure, and then extracted with dichloromethane, the organic phases were combined, washed with saturated sodium chloride, filtered, and spin-dried to obtain ligand L1 (2.394 g, 94%) by silica gel column chromatography.

[0033] 1 H NMR (400MHz, CDCl3) δ7.37–7.33(m,2H),7.31(dd,J=7.4,1.5Hz,2H),7.24–7.18(m,6H),7.16(dd,J=7.4,1.7Hz,2H),7.04(t,J=7.5Hz,2H),7.00(d, J=8.3Hz,2H),6.98–6.93(m,4H),6.86–6.82(m,2H),6.79(t,J=7.4Hz,2H) ,4.01(s,2H),3.86(d,J=13.5Hz,2H),3.77(s,6H),3.65(d,J=13.5Hz,2H).

[0034] Example 2, Preparation of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester and recycling of the catalyst system

[0035] The reaction formula is as follows:

[0036]

[0037] Zirconium acetylacetonate (0.098 g, 0.20 mmol), chiral ligand L1 (0.140 g, 0.22 mmol), and petroleum ether (70 mL) were added to a reaction flask and reacted at room temperature. After 30 minutes, 5-chloro-1-indanone-2-carboxylic acid methyl ester (2) (1.123 g, 5 mmol) and 70% aqueous solution of tert-butyl hydroperoxide (0.97 mL, 7.5 mmol) were added to the above reaction flask and continued to react at room temperature; after 24 hours, (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (1.095 g, 91%, ee 99%) was obtained by direct filtration and drying.

[0038] 1 H NMR (CDCl3, 400MHz): δ = 7.74 (d, J = 8.2Hz, 1H), 7.50 (s, 1H), 7.42 (d, J = 8.2Hz, 1H ),4.00(s,1H),3.75(s,3H),3.70(d,J=17.5Hz,1H),3.24(d,J=17.5Hz,1H).HPLC analysis CHIRALPAK OD-H, Hexane:i-PrOH=9:1, 25℃, 1.0mL / min flow rate, detection at 254nm, t1=12.12min (major), t2=14.50min (minor).

[0039] Second use of the catalyst system

[0040] To the filtrate obtained by filtration, 5-chloro-1-indanone-2-carboxylic acid methyl ester (2) (1.123 g, 5 mmol) and 70% aqueous solution of tert-butyl hydroperoxide (0.97 mL, 7.5 mmol) were added, and the reaction was continued at room temperature. After 24 hours, the mixture was directly filtered and dried to obtain (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (0.902 g, 75%, ee: 63%).

[0041] The catalytic system was used for the third time

[0042] To the filtrate obtained by filtering the catalyst system for the second time, 5-chloro-1-indanone-2-carboxylic acid methyl ester (2) (1.123 g, 5 mmol) and 70% aqueous solution of tert-butyl hydroperoxide (0.97 mL, 7.5 mmol) were added, and the reaction was continued at room temperature; after 24 hours, the mixture was directly filtered and dried to obtain (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (0.517 g, 43%, ee: 16%).

[0043] Example 3, the effect of solvent and oxidant on the preparation of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester According to the similar method described in Example 2, the effect of solvent and oxidant on the preparation of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester was investigated (Table 1). It can be seen from the results that if toluene commonly used in this type of reaction is used as a solvent, on the one hand, the reaction system requires strict anhydrous conditions and cumene hydroperoxide as an oxidant, and on the other hand, the product needs to be purified by column chromatography, and finally the product can be obtained with a yield of 99% and an ee value of 90% (Table 1 Experiments 1-6). If non-polar petroleum ether, n-hexane or cyclohexane is used as a solvent, the reaction not only does not require anhydrous reaction conditions, but also can use a more environmentally friendly and economical tert-butyl hydroperoxide 70% aqueous solution as an oxidant, and at the same time, the product can be purified by filtering only (Table 1 Experiments 7-11).

[0044] It should be noted that for industrial production, strict anhydrous conditions are not required and the product is purified only by filtering, which is very beneficial in terms of production cost, equipment requirements, operation convenience, and ease of scale-up production. At the same time, compared with the existing technology, the present invention replaces toluene with petroleum ether and replaces cumene hydroperoxide with tert-butyl hydroperoxide aqueous solution, which has significant advantages in terms of production cost and environmental friendliness.

[0045] Table 1 Effect of solvent and oxidant on the preparation of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester

[0046]

[0047] The above is only an embodiment of the present invention, and the common knowledge such as the known specific structure and characteristics in the scheme is not described in detail here. It should be pointed out that for those skilled in the art, several deformations and improvements can be made without departing from the structure of the present invention, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing a highly optically pure (S)-indoxacarb intermediate, characterized in that: A chiral Zr-Salan complex solution system is used as a catalyst, petroleum ether is used as a solvent, and a 70% aqueous solution of tert-butyl hydroperoxide is used as an oxidant. 5-chloro-1-indanone-2-carboxylic acid methyl ester (Formula 2) is added to carry out an asymmetric hydroxylation reaction to obtain (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester (Formula 1). The preparation method of the catalyst is as follows: a chiral ligand L1 and a zirconium-containing compound are reacted in a solvent at a certain temperature to generate a chiral Zr-Salan complex solution system; 2. The preparation method according to claim 1, characterized in that: The molar ratio of the chiral ligand L1 to the zirconium-containing compound is 0.5:1.0-4.0:1.

0.

3. The preparation method according to claim 2, characterized in that: The amount of the solvent used is 1 mL to 100 mL for every 0.1 mmol of the zirconium-containing compound.

4. The preparation method according to claim 3, characterized in that: The reaction temperature for the chiral ligand L1 and the zirconium-containing compound to react in a solvent to generate a chiral Zr-Salan complex is 0°C-60°C; the asymmetric hydroxylation reaction temperature is 0°C to 60°C.

5. The preparation method according to claim 4, characterized in that: The amount of the oxidant used is 20% to 500% of the molar amount of 5-chloro-1-indanone-2-carboxylic acid methyl ester.

6. The preparation method according to claim 5, characterized in that: The amount of the chiral Zr-Salan complex used is 0.1%-100% of the molar amount of 5-chloro-1-indanone-2-carboxylic acid methyl ester.

7. The preparation method according to claim 6, characterized in that: The zirconium-containing compound is zirconium hydroxide, zirconium oxychloride, zirconium oxide, zirconium acetylacetonate, zirconium trifluoroacetylacetonate, zirconium n-propoxide, zirconium tert-butoxide, zirconium phosphate, zirconium bromide or a mixture thereof.

8. The preparation method according to claim 7, characterized in that: The preparation method of the chiral ligand of the structure shown in L1 is as follows:

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