Synthesis method of alpha-position dichloro-substituted benzocyclic ketone compound

Abstract

The invention discloses a synthesis method for alpha-position dichloro-substituted benzocyclic ketone compounds, which comprises the following steps: adding NCS into a raw material compound in an organic solvent under the action of a catalyst to carry out chlorination reaction, and introducing two chlorine atoms to the alpha position of carbonyl to obtain a target compound. According to the invention, NCS, which is a common, economical and safe chlorination reagent, is used for reaction, and the product obtained by the synthesis method has the advantages of simple operation, small dosage of the chlorination reagent, cheap catalyst, small dosage and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a synthesis method of α-position dichloro-substituted benzocyclone compounds. Background Art

[0002] α-Chlorinated carbonyl compounds are important intermediates in organic synthesis because they can be transformed into a wide variety of molecules and can also serve as more metabolically stable alternatives to hydrogen and methyl functional groups in pharmaceuticals without losing therapeutic efficacy. These advantages have led to a strong interest in chlorination catalysis.

[0003] Although there are several reports on the reaction of dichloro substitution of α-position of benzocycloketone compounds, the chlorination reagents used are PhICl2, copper chloride, lithium chloride, and even highly toxic chlorine gas, which are neither economical, environmentally friendly, nor safe. It is difficult to achieve complete conversion under general conditions, and if two chlorines are added, by-products are easily generated under severe conditions. In the reactions reported so far, benzoxanone, aza- and thiocyclohexanone compounds are rarely used as substrates. Summary of the invention

[0004] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0005] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0006] One of the purposes of the present invention is to provide a method for synthesizing benzocyclone compounds with dichloro substitution at the α-position, wherein the raw materials can be completely chlorinated by NCS, and there are two chlorine atoms at the α-position of the carbonyl group, the reaction operation is simple, and the reaction yield is high.

[0007] In order to solve the above technical problems, the present invention provides the following technical solution: a method for synthesizing a benzocyclone compound with dichloro substitution at the α position, comprising:

[0008] The compound represented by structural formula I is added to the compound represented by structural formula II in an organic solvent in the presence of a catalyst to carry out a chlorination reaction, thereby introducing two chlorine atoms at the α position of the carbonyl group to obtain the compound represented by structural formula III;

[0009]

[0010]

[0011] Wherein, R is one of hydrogen, halogen, methyl, ethyl, methoxy, and nitro; X ​​is one of CH2, O, S, and NR', and R' is one of hydrogen, methyl, and tert-butyloxycarbonyl; and n is one of 0, 1, and 2.

[0012] As a preferred embodiment of the synthesis method of the α-position dichloro substitution of benzocyclone compounds of the present invention, the catalyst comprises one of ferric chloride, cupric chloride, zinc chloride, hydrochloric acid, sulfuric acid, formic acid and p-toluenesulfonic acid.

[0013] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclone compound of the present invention, the molar ratio of the catalyst to the compound represented by formula I is 0.01 to 0.1:1.

[0014] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclic ketone compound of the present invention, the molar ratio of the compound represented by formula I to the compound represented by formula II is 1:2-4.

[0015] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclone compound of the present invention, the organic solvent comprises one of acetonitrile, acetone, ethyl acetate, ethanol, methanol, tetrahydrofuran and dichloromethane.

[0016] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclone compound of the present invention, the chlorination reaction is carried out at a temperature of 40 to 100° C. and a reaction time of 1 to 8 hours.

[0017] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclone compound of the present invention, the chlorination reaction is carried out at a temperature of 100° C. and a reaction time of 4 hours.

[0018] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclic ketone compound of the present invention, the compound represented by structural formula I is selected from one of the following compounds:

[0019]

[0020] Wherein, R is one of hydrogen, halogen, methyl, ethyl, methoxy, and nitro; and R' is one of hydrogen, methyl, and tert-butyloxycarbonyl.

[0021] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclic ketone compound of the present invention, the compound represented by structural formula I is selected from one of the following compounds:

[0022]

[0023] Among them, R1 is one of hydrogen, halogen, methyl, methoxy, and nitro; R2 is one of hydrogen and chlorine; R3 is hydrogen; R4 is one of hydrogen, fluorine, and methoxy; R5 is hydrogen; R' is one of hydrogen, methyl, and tert-butyloxycarbonyl.

[0024] As a preferred embodiment of the synthesis method of the α-position dichloro-substituted benzocyclone compound of the present invention, it further comprises the step of purifying the reaction product.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The present invention uses NCS, a commonly used, economical and safe chlorination reagent, to react, and only needs to use a catalytic amount of a reaction catalyst, and the raw material can be completely chlorinated by NCS, with two chlorine atoms at the α position of the carbonyl group, and the product can be used as an intermediate of various drug molecules. The product obtained by the synthesis method has the advantages of simple operation, small amount of chlorination reagent, cheap catalyst and small amount of catalyst. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0028] Figure 1 is the H NMR spectrum of product II-a in Example 1 of the present invention;

[0029] Figure 2 is the H NMR spectrum of product II-g in Example 2 of the present invention;

[0030] Figure 3 is the H NMR spectrum of product II-i in Example 3 of the present invention;

[0031] Figure 4 is the H NMR spectrum of product II-aa in Example 8 of the present invention;

[0032] Figure 5 is the H NMR spectrum of the product II-ab in Example 9 of the present invention;

[0033] Figure 6 Schematic diagram of the synthesis steps in Example 15 of the present invention. DETAILED DESCRIPTION

[0034] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0035] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0036] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0037] Unless otherwise specified, the raw materials used in the examples were purchased commercially.

[0038] Example 1

[0039] Add 4-chromanone Ia (0.5mmol, 74mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-a, which is subsequently separated and purified by column chromatography to obtain a clean product II-a. Product yield = 99%, white solid. The nuclear magnetic hydrogen spectrum of the product II-a is as follows Figure 1 shown. 1 H NMR (500MHz, CDCl3) δ8.00 (dd, J=7.9, 1.7Hz, 1H), 7.58 (ddd, J=8.7, 7.2, 1.8Hz, 1H), 7.15 (ddd, J=8.1, 7.2, 1.1Hz, 1H), 7.05 (dd, J=8.4, 1.0Hz, 1H), 4.67 (s, 2H).

[0040] The reaction formula is:

[0041]

[0042] Example 2

[0043] Add 6-bromo-4-chromanone Ig (0.5mmol, 113mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-g, which is subsequently separated and purified by column chromatography to obtain a clean product II-g. Product yield = 96%, white solid. The nuclear magnetic hydrogen spectrum of the product II-g is as follows Figure 2 shown. 1 HNMR (500MHz, CDCl3) δ8.11(d,J=2.5Hz,1H),7.66(dd,J=8.9,2.5Hz,1H),6.97(d,J=8.8Hz,1H),4.68(s,2H).

[0044] The reaction formula is:

[0045]

[0046] Example 3

[0047] Add 6-nitro-4-chromanone Ii (0.5mmol, 97mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-i, which is subsequently separated and purified by column chromatography to obtain a clean product II-i. Product yield = 95%, white solid. The nuclear magnetic hydrogen spectrum of the product II-i is as follows Figure 3 shown. 1 HNMR (500MHz, CDCl3) δ8.91(d,J=2.8Hz,1H),8.44(dd,J=9.2,2.8Hz,1H),7.23(d,J=9.2Hz,1H),4.80(s,2H).

[0048] The reaction formula is:

[0049]

[0050] Example 4

[0051] 1-tetralinone Il (0.5mmol, 75mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) were added to the reaction bottle, heated to reflux for 4h, cooled to room temperature, the solvent was spin-dried, water was added to dissolve the product, and ethyl acetate (20mLx 3) was extracted three times to collect the organic phase. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-1, which was subsequently separated and purified by column chromatography to obtain a clean product II-1. Product yield = 99%, white solid. 1 H NMR (500MHz, CDCl3) δ7.92 (dd, J=8.2, 2.1Hz, 1H), 7.42 (ddd, J=7.9, 7.0, 2.1Hz, 1H), 7.37 (ddd, J=7.2,6.9,Hz,1H),7.35(dd,J=7.2,7.0,Hz,1H),3.03(t,J=5.1Hz,2H),2.73(t,J=5.1Hz,2H).

[0052] The reaction formula is:

[0053]

[0054] Example 5

[0055] Add 1-methyl-1,2,3,4-tetrahydroquinolin-4-one Iv (0.5mmol, 75mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-v, which is subsequently separated and purified by column chromatography to obtain a clean product II-v. Product yield = 95%, white solid. 1 H NMR (500MHz, CDCl3) δ7.90 (dd, J=7.5, 1.7Hz, 1H), 7.38 (ddd, J=8.5, 7.0, 1.5Hz, 1H), 6. 85(ddd,J=7.3,7.0,1.1Hz,1H),6.75(dd,J=8.4,1.5Hz,1H),4.50(s,2H),3.10(s,2H).

[0056] The reaction formula is:

[0057]

[0058] Example 6

[0059] Thiochroman-4-one Iw (0.5mmol, 75mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) were added to the reaction bottle, heated to reflux for 4h, cooled to room temperature, the solvent was spin-dried, water was added to dissolve the product, and ethyl acetate (20mLx 3) was extracted three times to collect the organic phase. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-w, which was subsequently separated and purified by column chromatography to obtain a clean product II-w. Product yield = 90%, white solid. 1 H NMR (500MHz, CDCl3) δ7.98 (dd, J=7.9, 1.5Hz, 1H), 7.58 (ddd, J=8.1, 7.0, 1.5Hz, 1 H), 7.05 (ddd, J=7.8, 7.0, 1.3Hz, 1H), 6.89 (dd, J=8.0, 1.5Hz, 1.2H), 4.60 (s, 2H).

[0060] The reaction formula is:

[0061]

[0062] Example 7

[0063] 1-Benzocycloheptanone Iy (0.5mmol, 75mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) were added to the reaction bottle, heated to reflux for 4h, cooled to room temperature, the solvent was spin-dried, water was added to dissolve the product, and ethyl acetate (20mLx 3) was extracted three times to collect the organic phase. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-y, which was subsequently separated and purified by column chromatography to obtain a clean product II-y. Product yield = 93%, white solid. 1 H NMR (500MHz, CDCl3) δ7.49(dd,J=7.5,1.3Hz,1H),7.43(dd,J=7.5,1.8Hz,1H),7.34(dd,J=7.5,0.9Hz,1H),7.17( d, J=7.5Hz, 1H), 2.85 (dd, J=7.0, 6.3Hz, 2H), 2.68 (dd, J=6.6, 5.7Hz, 2H), 2.08 (dddd, J=7.0, 6.6, 6.2, 5.7Hz, 2H).

[0064] The reaction formula is:

[0065]

[0066] Example 8

[0067] Add 5-methoxy-1-indanone I-aa (0.5mmol, 81mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-aa, which is subsequently separated and purified by column chromatography to obtain a clean product II-aa. Product yield = 93%, white solid. The nuclear magnetic hydrogen spectrum of the product II-aa is as follows Figure 4 shown. 1 H NMR (500MHz, CDCl3) δ7.85 (d, J=8.6Hz, 1H), 7.01 (dd, J=8.6, 2.3Hz, 1H), 6.86–6.80 (m, 1H), 4.00 (s, 2H), 3.92 (s, 3H).

[0068] The reaction formula is:

[0069]

[0070] Example 9

[0071] Add 5-fluoro-1-indanone I-ab (0.5mmol, 75mg), 10% p-toluenesulfonic acid (0.05mmol, 9mg), acetonitrile (5mL), N-chlorosuccinimide (1.25mmol, 167mg) to the reaction bottle, heat to reflux for 4h, cool to room temperature, spin dry the solvent, add water to dissolve the product, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product II-ab, which is subsequently separated and purified by column chromatography to obtain a clean product II-ab. The product yield = 98%, white solid. The nuclear magnetic hydrogen spectrum of the product II-ab is as follows Figure 5 shown. 1 H NMR (500MHz, CDCl3) δ7.95 (dd, J=8.5, 5.2Hz, 1H), 7.21 (td, J=8.7, 2.1Hz, 1H), 7.13–7.09 (m, 1H), 4.04 (s, 2H).

[0072] The reaction formula is:

[0073]

[0074] Example 10

[0075] Example 10 is basically the same as Example 1, except that the solvents are different, as shown in Table 1 below:

[0076] Table 1

[0077]

[0078]

[0079] As can be seen from Table 1, under the same reaction conditions, the target product can be obtained in all organic solvents; and the yield is higher in acetonitrile (MeCN), tetrahydrofuran (THF), and 2-methyltetrahydrofuran (2-MeTHF).

[0080] Embodiment 11

[0081] Example 11 is basically the same as Example 1, except that the catalyst is different, as shown in Table 2 below:

[0082] Table 2

[0083] catalyst Addition amount Yield (%) Ferric chloride 10％ 80％ Cupric chloride 10％ 50％ Zinc chloride 10％ 51％ hydrochloric acid 10％ 62％ sulfuric acid 10％ 77％ Formic acid 10％ 74％ p-Toluenesulfonic acid 1％ 80％ p-Toluenesulfonic acid 2％ 88％ p-Toluenesulfonic acid 5％ 97％ p-Toluenesulfonic acid 10％ 99％

[0084] As can be seen from Table 2, under the same reaction conditions (10% addition amount), the target product can be obtained under the catalysts of ferric chloride, cupric chloride, zinc chloride, hydrochloric acid, sulfuric acid, formic acid, p-toluenesulfonic acid, etc., and the yield is the highest in the p-toluenesulfonic acid catalyst. When the addition amount of the p-toluenesulfonic acid catalyst is reduced, the yield gradually decreases.

[0085] Example 12

[0086] Example 12 is basically the same as Example 1, except that the reaction temperature and reaction time are different, as shown in Table 3 below:

[0087] Table 3

[0088] temperature time Yield (%) 40℃ 4h 77％ 60℃ 4h 82％ 80℃ 4h 92％ 100℃ 4h 99％

[0089] It can be seen from Table 3 that under the same reaction conditions, the reaction temperature has a certain effect on the yield, among which the yield is highest when the reaction temperature is 100°C and the reaction time is 4h.

[0090] Embodiment 13

[0091] Example 13 is substantially the same as Example 1, except that the chlorination reagent is different, as shown in Table 4 below:

[0092] Table 4

[0093] Chlorination reagent Addition amount (equiv.) Yield (%) NCS 2.0 62％ NCS 2.1 71％ NCS 2.2 76％ NCS 2.3 85％ NCS 2.4 92％ NCS 2.5 99％ NCS 2.6 99％

[0094] It can be seen from Table 4 that under the same reaction conditions, the amount of chlorination reagent NCS added was changed. The higher the amount of NCS added, the higher the yield. The highest yield of 99% was reached at 2.5 equiv.

[0095] Embodiment 14

[0096] Example 14 is basically the same as Example 1, except that the reaction raw materials are different, as shown in Table 5 below:

[0097] Table 5

[0098]

[0099]

[0100]

[0101]

[0102] Embodiment 15

[0103] Examples 1 to 14 produce a series of 2,2-dichlorobenzocyclone compounds, which are important organic synthesis intermediates and can be further structurally modified and chemically transformed into various compounds.

[0104] Taking the 2,2-dichlorobenzocyclone compound II-z prepared in the example as an example, a compound V with TRPML channel activity can be obtained through a two-step synthesis. The synthesis process is as follows: Figure 6 shown.

[0105] The specific steps are:

[0106] (1) Synthesis steps of compound III:

[0107] Add II-z (1.0 mmol, 200 mg), concentrated sulfuric acid (3.0 mmol, 300 mg), and tetrahydrofuran (5 mL) to the reaction flask, heat to reflux for 8 h, cool to room temperature, and spin dry the solvent to obtain a crude product III, which is directly used in the next step without further purification.

[0108] (2) Synthesis steps of compound IV:

[0109] 1-(2-nitrophenyl)piperazine (1.0mmol, 177mg), triethylamine (304mg, 3.0mmol) were added to the reaction flask, dichloromethane (5mL) was added to dissolve and placed in an ice bath, pivaloyl chloride (181mg, 1.5mmol) was slowly added thereto, and the mixture was returned to room temperature after the addition was completed, and stirred for 8h. After the reaction was completed, water was added to quench, and the mixture was extracted three times with ethyl acetate (20mL x 3), and the organic phase was collected. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product, and a crude product IV was obtained, which was subsequently separated and purified by column chromatography to obtain a clean product IV. Product yield = 98%, 256mg, white solid.

[0110] (3) Synthesis steps of compound V:

[0111] Add crude III (0.5mmol, 140mg) to the reaction flask and place it in an ice bath. Slowly add phosphorus oxychloride (307mg, 2.0mmol) to it. Stir for 30min after the addition is completed. Then add compound IV (183mg, 0.7mmol) and pyridine (158mg, 2mmol) to the reaction flask, return to room temperature, stir for 4h, quench with water after the reaction is completed, extract three times with ethyl acetate (20mLx 3), and collect the organic phase. The organic phase is washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain a crude product to obtain a crude product V, which is subsequently separated and purified by column chromatography to obtain a clean product V. Product yield = 78%, 204mg, white solid.

[0112] The present invention uses NCS, a commonly used, economical and safe chlorination reagent, to react, and only needs to use a catalytic amount of a reaction catalyst, and the raw material can be completely chlorinated by NCS, with two chlorine atoms at the α position of the carbonyl group, and the product can be used as an intermediate of various drug molecules. The product obtained by the synthesis method has the advantages of simple operation, small amount of chlorination reagent, cheap catalyst and small amount of catalyst.

[0113] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.

Claims

1. A method for synthesizing a benzocyclone compound with dichloro substitution at the α position, characterized in that: include, The compound represented by structural formula I is added to the compound represented by structural formula II in an organic solvent in the presence of a catalyst to carry out a chlorination reaction, thereby introducing two chlorine atoms at the α position of the carbonyl group to obtain the compound represented by structural formula III; Wherein, R is one of hydrogen, halogen, methyl, ethyl, methoxy, and nitro; X ​​is one of CH2, O, S, and NR', R' is one of hydrogen, methyl, and tert-butyloxycarbonyl; and n is one of 0, 1, and 2.

2. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in claim 1, characterized in that: The catalyst includes one of ferric chloride, cupric chloride, zinc chloride, hydrochloric acid, sulfuric acid, formic acid and p-toluenesulfonic acid.

3. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in claim 2, characterized in that: The molar ratio of the catalyst to the compound represented by formula I is 0.01 to 0.1:

1.

4. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position according to any one of claims 1 to 3, characterized in that: The molar ratio of the compound represented by formula I to the compound represented by formula II is 1:2-4.

5. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in claim 4, characterized in that: The organic solvent includes one of acetonitrile, acetone, ethyl acetate, ethanol, methanol, tetrahydrofuran and dichloromethane.

6. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in any one of claims 1 to 3 and 5, characterized in that: The chlorination reaction is carried out at a temperature of 40 to 100° C. and a reaction time of 1 to 8 hours.

7. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in claim 6, characterized in that: The chlorination reaction was carried out at a temperature of 100° C. and a reaction time of 4 hours.

8. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in any one of claims 1 to 3, 5 and 7, characterized in that: The compound represented by structural formula I is selected from one of the following compounds: Wherein, R is one of hydrogen, halogen, methyl, ethyl, methoxy, and nitro; and R' is one of hydrogen, methyl, and tert-butyloxycarbonyl.

9. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position as claimed in claim 8, characterized in that: The compound represented by structural formula I is selected from one of the following compounds: Among them, R1 is one of hydrogen, halogen, methyl, methoxy, and nitro; R2 is one of hydrogen and chlorine; R3 is hydrogen; R4 is one of hydrogen, fluorine, and methoxy; R5 is hydrogen; R' is one of hydrogen, methyl, and tert-butyloxycarbonyl.

10. The method for synthesizing a benzocyclone compound with dichloro substitution at the α position according to any one of claims 1 to 3, 5, 7 and 9, characterized in that: The method also includes the step of purifying the reaction product.

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