A 3-(tert-butylperoxide)isoindolin-1-one derivative and its preparation method and use

Abstract

The present invention discloses a 3-(tert-butyl peroxide) isoindolin-1-one derivative and its preparation method and use, relating to the field of green synthetic chemistry technology, wherein the 3-(tert-butyl peroxide) isoindolin-1-one derivative is a racemate or an optically active stereoisomer of the R-configuration, and its preparation method includes using 3-hydroxyisoindolin-1-one compounds and tert-butyl hydroperoxide as starting materials, using ion exchange resin A-15 or chiral sulfonic acid as catalyst, and reacting in an organic solvent to obtain. The preparation method of the 3-(tert-butyl peroxide) isoindolin-1-one derivative disclosed in the present invention has the characteristics of mild reaction conditions, economic and environmental protection, green and efficient, and the catalyst used can be recycled multiple times. The obtained product has good biological activity and potential medical and pharmaceutical value.

Description

Technical Field

[0001] The present invention relates to the technical field of green synthesis, and in particular to a preparation method and application of a 3-(tert-butyl peroxide)isoindolin-1-one derivative. Background Art

[0002] Tri-substituted isoindolin-1-one derivatives and their optical isomers are commonly found in natural products and pharmaceutically active intermediates, such as the compounds shown in the following formula AC. These compounds have important pharmaceutical value and broad market application prospects.

[0003]

[0004] Furthermore, compounds containing peroxide structural units have also attracted research interest due to their significant biological activities. These molecules have been shown to exhibit remarkable anti-malarial, anti-tumor, and anti-cancer effects. Due to their unique biological activity, peroxides have found widespread application in organic synthesis, medicinal chemistry, and pesticide chemistry. Therefore, the present invention further investigates the biological and pharmacological activities of isoindolin-1-one compounds containing a peroxide substituent at the 3-position. Summary of the Invention

[0005] The present invention provides a preparation method and application of a 3-(tert-butyl peroxide)isoindolin-1-one derivative. The preparation method provides a new idea for the green and efficient synthesis of compounds containing peroxide skeleton structural units.

[0006] A 3-(tert-butylperoxy)isoindolin-1-one derivative, the structural formula of which is a racemate or (R)-configuration stereoisomer as shown in formula (I);

[0007]

[0008] wherein R2 is selected from hydrogen, C1-C6 alkyl or cycloalkyl, aryl or substituted aryl, benzyl; R1 is hydrogen, C1-C4 alkyl or alkoxy, halogen; the substituent on the substituted aryl is halogen, alkoxy, trifluoromethyl, C1-C6 alkyl or C1-C6 cycloalkyl;

[0009] Preferably, the structure of the 3-(tert-butyl peroxide)isoindolin-1-one derivative is:

[0010]

[0011] One of them.

[0012] The present invention also provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one derivatives, which has short reaction time, mild conditions and is easy to separate and purify.

[0013] A method for preparing 3-(tert-butyl peroxide)isoindolin-1-one derivatives comprises the following steps: using 3-hydroxyisoindolin-1-one compounds and tert-butyl hydroperoxide as raw materials, using commercial ion exchange resin Amberlyst-15 or chiral binaphthol-derived sulfonic acid as a catalyst, and reacting at 0-40° C. in an organic solvent as a reaction medium to obtain racemic or (R)-configured 3-(tert-butyl peroxide)isoindolin-1-one derivatives; the ion exchange resin A-15 and the 3-hydroxyisoindolin-1-one compound are added in a mass ratio of 5-20:100; and the chiral sulfonic acid catalyst and the 3-hydroxyisoindolin-1-one compound are added in a molar ratio of 0.05-0.1:1.

[0014] The structure of the preferred 3-hydroxyisoindolin-1-one compound is shown in the following formula (II):

[0015]

[0016] The preferred ion exchange resin Amberlyst-15 (A-15) is a commercial reagent purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd.

[0017] The structure of the preferred chiral sulfonic acid is shown in the following formula (III):

[0018]

[0019] Wherein, R is H, C6H5, 3,5-(CF3)2C6H3, 4-ClC6H4;

[0020] The definitions of R1-R2 in formula (II) are consistent with those in formula (I).

[0021] The preparation reaction equation of the 3-(tert-butyl peroxide)isoindolin-1-one derivative is as follows:

[0022]

[0023] The reaction principle is that under the catalysis of A-15 or chiral sulfonic acid, the hydroxyl group in 3-hydroxyisoindolin-1-one compounds and the hydrogen on the ortho-nitrogen are dehydrated to form an imine in situ. Then, tert-butyl hydroperoxide acts as a nucleophile to attack the in situ generated imine to obtain a chiral 3-(tert-butyl peroxy)isoindolin-1-one derivative.

[0024] More preferably, the 3-hydroxyisoindolin-1-one compound is:

[0025]

[0026] One of them.

[0027] Preferably, the organic solvent is at least one of acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, ethyl acetate, tetrahydrofuran or N,N-dimethylformamide.

[0028] Preferably, the ion exchange resin A-15 and the 3-hydroxyisoindolin-1-one compound are fed at a mass ratio of 5-20:100; or the chiral sulfonic acid catalyst and the 3-hydroxyisoindolin-1-one compound are fed at a molar ratio of 0.05-0.1:1.

[0029] Preferably, the 3-hydroxyisoindolin-1-one compound and tert-butyl hydroperoxide are added at a molar ratio of 1:1.0-5.0.

[0030] More preferably, the 3-hydroxyisoindolin-1-one compound and tert-butyl hydroperoxide are dissolved in an organic solvent, and A-15 or a chiral sulfonic acid catalyst is added at 0° C. to 40° C., and the stirring time is 0.25-2 h.

[0031] Preferably, after the reaction is completed, the reaction system is separated by ion exchange resin by filtration, the solvent is removed by rotary evaporation, and the product is preferably eluted with petroleum ether as an eluent to obtain a clean 3-(tert-butyl peroxy)isoindolin-1-one derivative.

[0032] Alternatively, after the reaction is completed, the solvent is removed by rotary evaporation, and the product is preferably eluted with saturated sodium bicarbonate solution and petroleum ether as eluents, thereby obtaining a clean 3-(tert-butylperoxy)isoindolin-1-one derivative.

[0033] Compared with the prior art, the preparation method of the present invention has the following advantages:

[0034] (1) No metal catalysis is required and the reaction can be carried out under mild conditions;

[0035] (2) The halogen, amide, and peroxy functional groups in 3-(tert-butylperoxy)isoindolin-1-one derivatives can be easily derivatized and transformed; in addition, the reaction efficiency can still be maintained in gram-scale experiments, which shows that this method has great practical value;

[0036] (3) Ion exchange resin can be recycled multiple times as a catalyst and reused repeatedly, which has important advantages in economy and environmental protection;

[0037] (4) Highly optically active 3-(tert-butylperoxy)isoindolin-1-one derivatives with nitrogen-containing quaternary stereocenters can be obtained, and the products have good pharmacological activity.

[0038] The present invention utilizes a Mannich reaction method catalyzed by a sulfonic acid ion exchange resin or a chiral catalyst to synthesize an isoindolin-1-one derivative containing a peroxide structural unit at the 3-position. The reaction conditions are mild, the process is simple, and the process is economical and green, which will be of great significance for new drug screening. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0040] Figure 1 3-(tert-butyl peroxide)isoindolin-1-one prepared in Example 1 of the present invention 1 H NMR spectrum;

[0041] Figure 2 3-(tert-butyl peroxide)isoindolin-1-one prepared in Example 1 of the present invention 13 C NMR spectrum;

[0042] Figure 3 This is the HPLC racemogram of chiral 3-(tert-butylperoxide)isoindolin-1-one prepared in Application Example 1 of the present invention;

[0043] Figure 4 This is the HPLC catalytic sample spectrum of chiral 3-(tert-butylperoxide)isoindolin-1-one prepared in Application Example 1 of the present invention. DETAILED DESCRIPTION

[0044] Based on the purpose of the present invention, the present invention provides a 3-(tert-butyl peroxide)isoindolin-1-one derivative, which is a racemate or an optically active stereoisomer with R-configuration. The preparation method comprises the steps of using 3-hydroxyisoindolin-1-one compounds and tert-butyl hydroperoxide as starting materials, and using ion exchange resin A-15 or chiral sulfonic acid as a catalyst to react in an organic solvent to obtain the derivative. The structure of the derivative is shown in Formula (I):

[0045]

[0046] In the formula: R2 is selected from hydrogen, C1-C6 alkyl or cycloalkyl, aryl or substituted aryl, benzyl, R1 is hydrogen, C1-C4 alkyl or alkoxy, halogen; the substituent on the substituted aryl is halogen, alkoxy, trifluoromethyl, C1-C6 alkyl or C1-C6 cycloalkyl.

[0047] The structure of the 3-hydroxyisoindolin-1-one compound in the preparation method of the present invention is shown in the following formula (II):

[0048]

[0049] The definitions of R1-R2 in formula (II) are consistent with those in formula (I).

[0050] The structure of the chiral sulfonic acid in the preparation method is shown in the following formula (III):

[0051]

[0052] Wherein, R is H, C6H5, 3,5-(CF3)2C6H3, 4-ClC6H4;

[0053] The preparation reaction equation is as follows:

[0054]

[0055] The reaction principle of the present invention is that under the catalysis of A-15 or chiral sulfonic acid, the hydroxyl group in the 3-hydroxyisoindolin-1-one compound and the hydrogen on the ortho-nitrogen are dehydrated to form an imine in situ, and then tert-butyl hydroperoxide acts as a nucleophile to attack the in situ generated imine to obtain a chiral 3-(tert-butyl peroxy)isoindolin-1-one derivative.

[0056] Based on the above embodiments, the technical solution of the present invention is further described below through examples.

[0057] Example 1

[0058] This example provides a method for preparing 3-(tert-butylperoxide)isoindolin-1-one. The specific steps and parameters are as follows: 3-hydroxy-3-phenylisoindolin-1-one (0.2 mmol, 45 mg), a decane solution of tert-butyl hydroperoxide (0.05 mmol), and an ion exchange resin A-15 (10% w, 4.5 mg) were added to a clean, dry 10 mL reaction bottle. 2 mL of acetonitrile was added and the reaction was allowed to proceed at room temperature. The reaction was monitored by TLC for 0.5 hours until completion. The ion exchange resin was filtered to remove the solvent, and the crude product was spun off to obtain a crude product. The crude product was washed with petroleum ether and dried to obtain pure 3-(tert-butylperoxide)isoindolin-1-one (II) in a yield of 97%. The product was characterized as follows:

[0059] Structural formula:

[0060]

[0061] Appearance: white solid;

[0062] Melting point: 175-177°C;

[0063] 1 H NMR (400MHz, CDCl3): δ7.81(dd,J=5.7,2.5Hz,1H),7.61(dd,J=8.0,1.6Hz,2H),7.51–7.46(m,2H),7.40–7.31(m,4H),6.66(s,1H),1.20(s,9H);

[0064] 13 C NMR (101MHz, CDCl3): δ169.0,144.8,136.8,131.4,129.7,128.7,127.9,127.7,124.9,122.6,122.4,93.7,79.8,25.5;

[0065] HRMS: Theoretical value C 18 H 19 NO3320.1257, detection value is 320.1259.

[0066] Example 2

[0067] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is 4-methylphenyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-2) was obtained with a yield of 93%. The product is characterized as follows:

[0068] Structural formula:

[0069]

[0070] Melting point: 186-188°C;

[0071] 1 H NMR (400MHz, CDCl3): δ7.72(d,J=6.7Hz,1H),7.43(d,J=8.1Hz,2H),7.40–7.35(m,2H) ,7.25(d,J=7.4Hz,1H),7.11(d,J=8.0Hz,2H),7.00(s,1H),2.26(s,3H),1.11(s,9H);

[0072] 13C NMR (101MHz, CDCl3): δ169.1,145.0,137.8,133.8,131.4,129.7,128.5,128.4,124.8,122.5,122.3,93.8,79.7,25.5,20.1;

[0073] HRMS: Theoretical value C 19 H 21 NO3334.1414, detection value is 334.1417.

[0074] Example 3

[0075] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is 4-fluorophenyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-3) was obtained with a yield of 98%. The product is characterized as follows:

[0076] Structural formula:

[0077]

[0078] Melting point: 145-147°C;

[0079] 1 H NMR (400MHz, CDCl3): δ7.87 (dd, J=5.4, 3.0Hz, 1H), 7.82 (dd, J=5.9, 2.6Hz, 1H), 7.76 (dd, J=5.4, 3.1H z,1H),7.61–7.58(m,2H),7.53–7.47(m,2H),7.30–7.28(m,1H),6.96(d,J=16.3Hz,1H),1.20(s,9H);

[0080] 13 C NMR (101MHz, CDCl3): δ169.0,144.5,133.3,131.6,129.5,128.8,126.9(d,J =8.6Hz), 122.6, 122.5 (d, J = 45.5Hz), 114.6 (d, J = 21.5Hz), 93.4, 80.0, 25.5;

[0081] 19 F NMR(376MHz, CDCl3)δ-113.0(s);

[0082] HRMS: Theoretical value C 18 H18 FNO3338.1163, detection value is 338.1163.

[0083] Example 4

[0084] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is 3-trifluoromethylphenyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-4) was obtained with a yield of 87%. The product is characterized as follows:

[0085] Structural formula:

[0086]

[0087] Melting point: 145-147°C;

[0088] 1 H NMR (400MHz, CDCl3): δ7.91(s,1H),7.84–7.80(m,2H),7.62(d,J=7.7Hz,1H),7.53–7.50(m,3H),7.29–7.27(m,1H),7.23(s,1H),1.22(s,9H);

[0089] 13 C NMR (101MHz, CDCl3): δ169.1, 143.9, 138.3, 131.8, 130.1 (d, J = 32.4Hz), 129.5, 129.2, 128.5, 128.2, 124.7 (d, J = 3.7Hz), 123.0, 122.4, 122.0 (d, J = 3.9Hz), 93.4, 80.3, 25.5;

[0090] 19 F NMR(376MHz, CDCl3)δ-62.6(s);

[0091] HRMS: Theoretical value C 19 H 18 F3NO3388.1131, detection value is 388.1130.

[0092] Example 5

[0093] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2The substituent is 2-tolyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-5) was obtained with a yield of 92%. The product is characterized as follows:

[0094] Structural formula:

[0095]

[0096] Melting point: 163-165°C;

[0097] 1 H NMR (400MHz, CDCl3): δ7.77–7.68(m,2H),7.44–7.42(m,2H),7.20–7.14(m,3H),7.07–7.05(m,1H),6.80(s,1H),2.10(s,3H),1.11(s,9H);

[0098] 13 C NMR (101MHz, CDCl3): δ169.1,144.1,135.2,134.0,131.5,131.5,130.7,128.8,127.9,126.7,124.9,122.7,122.5,94.0,79.8,25.5,19.9;

[0099] HRMS: Theoretical value C 19 H 21 NO3334.1414, detection value is 334.1419.

[0100] Example 6

[0101] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is 3,5-dimethylbenzyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-6) was obtained with a yield of 86%. The product is characterized as follows:

[0102] Structural formula:

[0103]

[0104] Melting point: 171-173°C;

[0105] 1H NMR (400MHz, CDCl3): δ7.81–7.67(m,3H),7.44–7.37(m,2H),7.27(d,J=7.0Hz,1H),6.91(s,1H),6.76(s,1H),2.24(s,6H),1.12(s,9H);

[0106] 13 C NMR (101MHz, CDCl3): δ169.1,145.0,137.4,136.6,133.2,131.7,131.4,130.7,129.6,128.5,122.6,122.5,122.4,93.7,79.7,25.5,20.4;

[0107] HRMS: Theoretical value C 20 H 23 NO3348.1570, detection value is 348.1573.

[0108] Example 7

[0109] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is methyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-7) was obtained with a yield of 81%. The product is characterized as follows:

[0110] Structural formula:

[0111]

[0112] Melting point: 100-102°C;

[0113] 1 H NMR (400MHz, CDCl3): δ7.72(d,J=7.4Hz,1H),7.50(d,J=7.7Hz,1H),7.43(t,J=7.5Hz,2H),6.81(s,1H),1.73(s,3H),1.07(s,9H);

[0114] 13 C NMR (101MHz, CDCl3): δ168.3,144.6,131.3,130.6,128.7,122.5,121.3,91.2,79.3,25.4,21.4;

[0115] HRMS: Theoretical value C 13 H 17NO3258.1101, detection value is 258.1100.

[0116] Example 8

[0117] This embodiment provides a method for preparing 3-(tert-butyl peroxide)isoindolin-1-one. The specific steps and parameters are the same as those in Example 1, except that R 2 The substituent is phenylethynyl. Finally, pure 3-(tert-butylperoxy)isoindolin-1-one (I-8) was obtained with a yield of 88%. The product is characterized as follows:

[0118] Structural formula:

[0119]

[0120] Melting point: 118-120℃;

[0121] 1 H NMR (400MHz, CDCl3): δ7.86–7.83(m,1H),7.71(d,J=7.5Hz,1H),7.64(t,J=7.3Hz,1H), 7.57(t,J=7.3Hz,1H),7.46–7.44(m,2H),7.37–7.29(m,3H),7.14(s,1H),1.27(s,9H);

[0122] 13 C NMR (101MHz, CDCl3): δ167.8,142.2,133.2,132.0,130.9,129.6,128.1,127.3,122.8,122.5,120.4,85.6,84.2,82.8,80.6,25.5;

[0123] HRMS: Theoretical value C 20 H 19 NO3344.1257, detection value is 344.1258.

[0124] Application Example 1

[0125] This example provides a method for preparing optically active 3-(tert-butylperoxy)isoindolin-1-one. The specific steps and parameters are as follows: 3-hydroxy-3-phenylisoindolin-1-one (0.2 mmol, 45 mg), a decane solution of tert-butyl hydroperoxide (0.05 mmol), and a chiral sulfonic acid catalyst (0.002 mmol, 4.5 mg) were added to a clean, dry 10 mL reaction bottle. 2 mL of dichloromethane was added as a solvent, and the reaction was carried out under ice-water conditions for 24 hours. The product was purified by column chromatography to obtain chiral 3-(tert-butylperoxy)isoindolin-1-one (II) in a yield of 70% and 97% ee.

[0126] Figure 3 and Figure 4 For Application Example 1, Figure 3 The racemate obtained under the catalytic conditions of A-15 was analyzed by high-performance liquid chromatography, and it can be seen that the R or S configuration each accounts for 50%. When the reaction was catalyzed by a chiral sulfonic acid catalyst, it can be seen that the control effect on the chiral configuration was very obvious under the same liquid phase conditions, and a chiral compound with a single chiral configuration was obtained.

[0127] The corresponding liquid phase separation conditions were: Agilent HPLC 1260-I, Daicel Chiralpak AD-H, hexane / 2-iPopanol=92:8, v=1.0 mL / min, wavelength=220 nm.

[0128] Application Example 2

[0129] This example provides a scaled-up preparation method for 3-(tert-butylperoxide)isoindolin-1-one. The specific steps and parameters are as follows: 3-hydroxy-3-phenylisoindolin-1-one (20 mmol, 4.5 g), a decane solution of tert-butyl hydroperoxide (5.0 mmol), and A-15 (450 mg) were added to a clean, dry 100 mL reaction flask. 100 mL of acetonitrile was added as a solvent, and the mixture was stirred at room temperature for 24 hours. The reaction was then filtered and concentrated to obtain 3-(tert-butylperoxide)isoindolin-1-one (II) in a yield of 90%.

[0130] Application Example 3

[0131] This example provides a method for determining the cytotoxicity of a derivative (I-3) of 3-(tert-butylperoxy)isoindolin-1-one. The specific steps and parameters are as follows:

[0132] For cell culture, the cell lines used were purchased from the American Type Culture Collection, and rat glioma cell line C6 was cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS). The cells were cultured at 37°C in a humidified atmosphere containing 5% carbon dioxide.

[0133] The cytotoxicity of the compounds was evaluated by MTT assay using C6 cells. 4 Cells were seeded at a density of 100 μg / well in a 96-well tissue culture plate, and each well was then replaced with 0.1 mL of DMSO and measured spectrophotometrically at a wavelength of 570 nm in an ELISA plate reader (Model 550, Bio-Rad). Relative cell growth (V) relative to control cells cultured in medium without compound was calculated by the following formula: V% = ([A] experimenta1 -[A] blank ) / ([A] contro1 -[A] blank )×100%

[0134] Where, [A] experimenta1 is the absorbance value of drug-treated cell wells; [A] blan k is the absorbance value of the well containing culture medium but no cells; [A] control is the absorbance value of the well without treatment

[0135] Cytotoxicity test against rat glioma cell line C6, IC of compound I-3 50 The value is 8.2μM. The test results show that this series of compounds has good biological activity.

[0136] Based on the technical concept of the present invention, the present invention provides a series of 3-(tert-butyl peroxide)isoindolin-1-one derivatives shown in general formula (I). The obtained series of 3-(tert-butyl peroxide)isoindolin-1-one derivatives are racemates or optically active stereoisomers of R-configuration, which are obtained by reaction in an organic solvent using 3-hydroxyisoindolin-1-one compounds and tert-butyl hydroperoxide as starting materials and ion exchange resin A-15 or chiral sulfonic acid as catalyst. Furthermore, the present invention conducted an amplification experiment on the 3-(tert-butyl peroxide)isoindolin-1-one obtained in Example 1. The results showed that the yield after the amplification experiment reached 90%, which can be fully applied to actual production. Furthermore, the present invention conducted a cytotoxicity test on the 3-(tert-butyl peroxide)isoindolin-1-one derivative (I-3) obtained in Example 3. In the cytotoxicity test on the rat glioma cell line C6, the IC of compound I-3 was 0. 50 The value is 8.2μM. The test results show that this series of compounds has good biological activity.

[0137] It should be further clarified that the above examples are intended solely to facilitate understanding of the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. While the application examples do not include scale-up experiments and cytotoxicity tests for all specific derivatives of the general formula of the present invention, it is expected that the derivatives obtained by the present invention will have the same technical effects as those in the experimental examples. Any obvious adjustments and modifications to the technical solutions of the present invention that fall within the technical concept of the present invention are intended to fall within the scope of protection of the present invention.

Claims

1. A 3-(tert-butylperoxy)isoindolin-1-one derivative, characterized in that: Its structure is: One of them.

2. The method for preparing a 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 1, wherein: The method is prepared by using 3-hydroxyisoindolin-1-one compounds and tert-butyl hydroperoxide as starting materials, ion exchange resin Amberlyst-15 or chiral sulfonic acid as catalyst, and an organic solvent as the reaction medium under the condition of 0-40°C. The structure of the 3-hydroxyisoindolin-1-one compound is: One of the following; The ion exchange resin Amberlyst-15 is a commercial reagent; the structure of the chiral sulfonic acid is shown in the following formula (III): Among them, R is H, C6H5, 3,5-(CF3)2C6H3, 4-ClC6H4.

3. The method for preparing 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 2, characterized in that: The organic solvent is at least one of acetonitrile, dichloromethane, 1,2-dichloroethane, chloroform, benzene, toluene, xylene, ethyl acetate, tetrahydrofuran or N,N-dimethylformamide.

4. The method for preparing 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 3, characterized in that: The ion exchange resin Amberlyst-15 and the 3-hydroxyisoindolin-1-one compound are added in a mass ratio of 5-20:100; or the chiral sulfonic acid catalyst and the 3-hydroxyisoindolin-1-one compound are added in a molar ratio of 0.05-0.1:

1.

5. The method for preparing 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 3, characterized in that: The 3-hydroxyisoindolin-1-one compound and tert-butyl hydroperoxide are added in a molar ratio of 1:1.0-5.

0.

6. The method for preparing 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 3, characterized in that: The 3-hydroxyisoindolin-1-one compound and tert-butyl hydroperoxide are dissolved in an organic solvent, and an ion exchange resin Amberlyst-15 or a chiral sulfonic acid catalyst is added at 0° C. to 40° C., and the stirring time is 0.25-2 hours.

7. The method for preparing a 3-(tert-butylperoxy)isoindolin-1-one derivative according to any one of claims 2 to 6, characterized in that: The method further comprises the following steps: after the reaction is completed, separating the reaction system by ion exchange resin by filtration, removing the solvent by rotary evaporation, and eluting the product with petroleum ether as an eluent to obtain a clean 3-(tert-butylperoxy)isoindolin-1-one derivative; Alternatively, after the reaction is completed, the solvent is removed by rotary evaporation, and the product is eluted with saturated sodium bicarbonate solution and petroleum ether as eluents, thereby obtaining a clean 3-(tert-butylperoxy)isoindolin-1-one derivative.

8. Use of a 3-(tert-butylperoxy)isoindolin-1-one derivative according to claim 1 in the preparation of a drug for treating rat glioma cell line C6.

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