CN108329197A - A kind of preparation method of indanone compounds - Google Patents

Abstract

The invention relates to the field of organic synthesis, in particular to a preparation method of indanone compounds. The invention provides a preparation method of indanone compounds, comprising: 1) performing a condensation reaction on a compound of formula I and a compound of formula II to prepare a compound of formula III; 2) hydrolyzing the compound of formula III in the presence of a base to prepare Obtain the compound of formula IV; 3) acylate and ring-close the compound of formula IV to obtain the compound of formula V. Compared with the prior art, the preparation method of the indenone compounds provided by the present invention has the advantages of low raw material cost, simple and convenient operation, less waste, and high yield, and is more suitable for industrial production. Compared with various indenones in the prior art The preparation method of ketone compounds has obvious advantages and has good industrialization prospects.

Description

A kind of preparation method of indanone compound

technical field

The invention relates to the field of organic synthesis, in particular to a preparation method of indanone compounds.

Background technique

Indanone compounds are important raw materials for the synthesis of polyolefins, especially metallocene catalysts for polyα-olefins, and are also important intermediates for the synthesis of fine chemicals such as pesticides, liquid crystals, and active pharmaceutical components.

In existing literature reports, some synthetic methods of indanone compounds have been disclosed, such as European Journal of Medicinal Chemistry, 2013, 62, 632-648, Molecules, 2014, 19, 5599-5610, Organometallics 2006, 25, 1217-1229 and WO2007/070041, EP 0576970 A1, US4192888 A1, US2002077507. The main methods for preparing indenones in the report are:

1, take benzaldehyde as the synthetic method of raw material:

Use substituted benzaldehyde as raw material, react with substituted malonate through condensation and decarboxylation to obtain 3-substituted phenyl-2-substituted acrylic acid, and then catalyze by hydrogenation, acid chloride, aluminum trichloride or polyphosphoric acid Cyclization to synthesize indanones (Organometallics 2006, 25, 1217-1229).

Using substituted benzaldehyde as raw material, perkin reaction with acid anhydride, hydrogenation, acyl chloride, Friedel-Crafts cyclization of aluminum trichloride to synthesize indanones (European Journal of Medicinal Chemistry, 2013, 62, 632-648).

2. Using substituted aromatic hydrocarbons as raw materials:

The method uses substituted aromatic hydrocarbons as raw materials, catalyzed reaction with 2-substituted propionyl chloride in aluminum trichloride to generate substituted phenyl ethyl ketone, and then undergoes bromination, aluminum trichloride catalyzed cyclization, and hydrolysis to obtain indanone compounds (US2002077507).

3. Using substituted benzyl halides as raw materials:

The method mainly uses substituted benzyl halides such as benzyl chloride as raw materials to synthesize, and reacts benzyl halides with substituted malonates to generate substituted phenylpropionic acid compounds, which are then catalyzed by acyl chloride, aluminum trichloride or phosphoric acid-containing compounds. Further synthesis of indanone compounds (US2007/0135595 A1).

In the method provided by the above-mentioned documents, the cost of raw materials is high, the reaction route is long, and the operation is complicated, and the existing process uses a phosphorus-containing raw material, which will produce a large amount of phosphorus-containing wastewater, and the treatment of phosphorus-containing wastewater will greatly increase the manufacturing cost of the product. adverse effects on the environment. Therefore, it is one of the important goals for those skilled in the art to develop a simple and low-cost green synthetic method suitable for industrial production of indanones.

Contents of the invention

In view of the above-mentioned shortcomings of the prior art, the object of the present invention is to provide a preparation method of indanone compounds for solving the problems in the prior art.

In order to achieve the above object and other related objects, the present invention provides a method for preparing indanone compounds, comprising:

1) Condensing the compound of formula I with the compound of formula II to prepare the compound of formula III;

2) hydrolyzing the compound of formula III in the presence of a base to prepare the compound of formula IV;

3) Acylate and ring-close the compound of formula IV to prepare the compound of formula V;

The structural formula of the compound of formula I-V is as follows:

Wherein, R1, R2, R3, R4 are each independently selected from H, Cl, Br, I, F, straight chain or branched C1-C18 alkyl;

R5 is selected from H, Cl, Br, straight chain or branched C1-C18 alkyl;

R6 is selected from linear or branched C1-C18 alkyl groups.

X is selected from Cl or Br.

In some embodiments of the present invention, R1, R2, R3, and R4 are each independently selected from H, Cl, Br, F, and linear or branched C1-C8 alkyl groups.

In some embodiments of the present invention, R1, R2, R3, R4 are each independently selected from H, Cl, straight chain or branched C1-C4 alkyl.

In some embodiments of the present invention, R5 is selected from linear or branched C1-C10 alkyl groups.

In some embodiments of the present invention, R5 is selected from linear or branched C1-C4 alkyl groups.

In some embodiments of the present invention, R6 is selected from linear or branched C1-C8 alkyl groups.

In some embodiments of the present invention, R6 is selected from linear or branched C1-C4 alkyl groups.

In some embodiments of the present invention, in the step 1), the molar ratio of the compound of formula I to the compound of formula II is 1-6:1.

In some embodiments of the present invention, in the step 1), the molar ratio of the compound of formula I to the compound of formula II is 1-3:1.

In some embodiments of the present invention, in the step 1), the reaction is carried out in the presence of a base.

In some embodiments of the present invention, in the step 1), the base is selected from one or more combinations of alkali metal organic salts, alkali metal carbonates, sodium amide or sodium hydride.

In some embodiments of the present invention, in the step 1), the base is selected from sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, n-butyllithium, LDA, sodium hydride, A combination of one or more of sodium amide, sodium carbonate, and potassium carbonate.

In some embodiments of the present invention, in the step 1), the molar ratio of the base to the compound of formula II is 1-5:1.

In some embodiments of the present invention, in the step 1), the molar ratio of the base to the compound of formula II is 1-3:1.

In some embodiments of the present invention, in the step 1), the reaction is carried out in the presence of a solvent.

In some embodiments of the present invention, in the step 1), the solvent is selected from organic solvents.

In some embodiments of the present invention, in the step 1), the organic solvent is selected from ether solvents.

In some embodiments of the present invention, in the step 1), the ether solvent is selected from one or more of diethyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran The combination.

In some embodiments of the present invention, in the step 1), the reaction temperature is 0-120°C.

In some embodiments of the present invention, in the step 1), the reaction temperature is 20-50°C.

In some embodiments of the present invention, in the step 1), post-treatment of the reaction includes adding water to quench.

In some embodiments of the present invention, in the step 2), the base is selected from NaOH and/or KOH.

In some embodiments of the present invention, in the step 2), the molar ratio of the base to the compound of formula III is 1-6:1, preferably 1-3:1.

In some embodiments of the present invention, in the step 2), the reaction temperature is 0-100°C.

In some embodiments of the present invention, in the step 2), the reaction temperature is 30-60°C.

In some embodiments of the present invention, in the step 2), post-treatment of the reaction includes: liquid separation, adjusting the pH of the obtained aqueous phase to 2.0-5.0, and collecting the organic phase.

In some embodiments of the present invention, in the step 3), the reaction is carried out in the presence of a solvent.

In some embodiments of the present invention, in the step 3), the solvent is selected from an organic solvent, and the organic solvent is selected from one of dichloromethane, dichloroethane, toluene, chlorobenzene, nitromethane, and nitroethane. one or more combinations.

In some embodiments of the present invention, in the step 3), the acylation reaction is carried out in the presence of an acylating reagent, and the molar ratio of the acylating reagent to the compound of formula IV is 1-3:1.

In some embodiments of the present invention, in the step 3), the acylating agent is selected from thionyl chloride and/or oxalyl chloride.

In some embodiments of the present invention, in the step 3), the reaction temperature of the acylation reaction is 0-100°C.

In some embodiments of the present invention, in the step 3), the ring closure reaction is carried out in the presence of a Lewis acid.

In some embodiments of the present invention, in the step 3), the Lewis acid is selected from one or more of aluminum trichloride, zinc chloride, ferric chloride, tin tetrachloride, and aluminum tribromide combination.

In some embodiments of the present invention, in the step 3), in the step 3), the molar ratio of the Lewis acid to the compound of formula IV is 1-3:1.

In some embodiments of the present invention, in the step 3), in the step 3), the molar ratio of the Lewis acid to the compound of formula IV is 1.2-2:1.

In some embodiments of the present invention, in the step 3), the reaction temperature of the ring closure reaction is 0-100°C.

In some embodiments of the present invention, in the step 3), post-treatment of the reaction includes: quenching, liquid separation, precipitation of the organic phase, and purification to obtain the indanone compound.

In some embodiments of the present invention, in the step 3), the purification method is rectification and/or recrystallization.

Detailed ways

After a lot of research, the inventors of the present invention provided a method for preparing indanone compounds through condensation, hydrolysis, acylation, and ring closure. The preparation method is low in cost, simple and easy to implement, and completed the present invention .

One aspect of the present invention provides a preparation method of indanone compounds, the structural formula of the indenone compounds is shown in the compound of formula V, and the preparation method may include:

1) Condensing the compound of formula I with the compound of formula II to prepare the compound of formula III;

2) hydrolyzing the compound of formula III in the presence of a base to prepare the compound of formula IV;

3) Acylate and ring-close the compound of formula IV to prepare the compound of formula V;

The structural formula of the compound of formula I-V is as follows:

In the preparation method of indanone compounds provided by the present invention, R1, R2, R3, R4 can each independently be selected from H, Cl, Br, I, F, straight chain or branched C1-C18 alkyl, more Preferably selected from H, Cl, Br, F, straight chain or branched C1-C8 alkyl, more preferably selected from H, Cl, straight chain or branched C1-C4 alkyl; R5 can be selected from H, Cl , Br, linear or branched C1-C18 alkyl, more preferably selected from linear or branched C1-C10 alkyl, further preferably selected from linear or branched C1-C4 alkyl; R6 can be selected A straight chain or branched chain alkyl group from C1-C18, more preferably selected from straight chain or branched chain C1-C8 alkyl group, further preferably selected from straight chain or branched chain C1-C4 alkyl group; X can be selected from Cl or Br. . The C1-C4 alkyl group may specifically be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl and the like.

In the preparation method of the indanone compounds provided by the present invention, in the condensation reaction, the compound of formula I is usually substantially equal or excessive in moles with respect to the compound of formula II, for example, the molar ratio of the compound of formula I and the compound of formula II can be 1 to 6:1, or 1 to 3:1.

In the preparation method of indanone compounds provided by the present invention, the condensation reaction is usually carried out in the presence of a base, which can be, for example, alkali metal organic salts, alkali metal carbonates, sodium amide, sodium hydride, etc. One or more combinations, more specifically sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide, n-butyllithium, LDA, sodium hydride, sodium amide, sodium carbonate , Potassium carbonate, etc. one or more combination. The molar amount of the base relative to the compound of formula II is usually substantially equal or in excess, for example, the molar ratio of the base to the compound of formula II is 1-5:1, and may also be 1-3:1.

In the preparation method of indanone compounds provided by the present invention, the condensation reaction is usually carried out in the presence of a solvent, and the solvent used in the condensation reaction is usually an organic solvent, and those skilled in the art can select a suitable organic solvent according to the reaction substrate The type and usage amount, so that the reaction substrate can be fully dispersed in the reaction system, for example, the solvent used in the condensation reaction can be such as ether solvents, more specifically can be such as diethyl ether, methyl tert-butyl ether, One or more combinations of dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, etc., in a preferred embodiment of the present invention, the solvent used in the condensation reaction is tetrahydrofuran; another example, the solvent used in the condensation reaction The dosage can be 1-20 times the mass of the compound of formula II.

In the preparation method of indanone compounds provided by the present invention, the condensation reaction can usually be carried out at a temperature not higher than the boiling point of the solvent or from room temperature to the boiling point of the solvent. For example, the temperature of the condensation reaction can be 0-120 ° C, or it can be 20-50°C. Those skilled in the art can suitably adjust the reaction time of the condensation reaction according to the reaction process, and the method for monitoring the reaction process should be known to those skilled in the art, such as analytical methods such as chromatography and nuclear magnetic resonance. The specific reaction The time can be, for example, 1-5 hours.

In the preparation method of the indanone compounds provided by the present invention, those skilled in the art can select a suitable post-treatment method to post-process the product obtained from the condensation reaction. For example, after the reaction is completed, the post-treatment of the condensation reaction can include: Add water to the system to quench. In a preferred embodiment of the present invention, the reaction solution obtained by quenching with water can be directly used in subsequent reaction steps.

In the preparation method of the indanone compounds provided by the present invention, those skilled in the art can select suitable types of alkali to provide the basic conditions required for hydrolysis, for example, the alkali can be NaOH and/or KOH, during the hydrolysis process The molar ratio of the base to the compound of formula III is usually substantially equal or in excess, for example, the molar ratio of the base to the compound of formula III can be 1-6:1, or 1-3:1.

In the preparation method of indanone compounds provided by the present invention, the hydrolysis reaction can usually be carried out at a temperature not higher than the boiling point of the solvent or from room temperature to the boiling point of the solvent. For example, the temperature of hydrolysis can be 0-100 ° C, or it can be 30-60°C. Those skilled in the art can suitably adjust the reaction time of hydrolysis according to the reaction process, and the method for monitoring the reaction process should be known to those skilled in the art, such as analytical methods such as chromatography and nuclear magnetic resonance, and the specific reaction time It can be, for example, 1-5 hours.

In the preparation method of the indanone compounds provided by the present invention, those skilled in the art can select a suitable post-treatment method to post-treat the product obtained by hydrolysis. For example, after the reaction is completed, the post-treatment of hydrolysis may include: liquid separation , the resulting aqueous phase is adjusted to pH 2.0-5.0, and the organic phase is collected. Those skilled in the art can select a suitable pH value regulator to adjust the pH value of the reaction system, for example, applicable HCl, H ₃ PO4, H ₂ SO ₄ , CH ₃ COOH or their aqueous solutions, etc.

In the preparation method of the indanone compound provided by the present invention, the acylation reaction and/or the ring closure reaction can be carried out under the condition that organic solvent exists, those skilled in the art can select the type and the suitable organic solvent according to the reaction substrate. Use amount, so that the reaction substrate can be fully dispersed in the reaction system, for example, the organic solvent used in the acylation reaction and/or ring-closing reaction can be a halogenated hydrocarbon solvent, a nitro compound solvent, etc., more Specifically, it can be, for example, a combination of one or more of dichloromethane, dichloroethane, toluene, chlorobenzene, nitromethane, nitroethane, etc.; another example, in the acylation reaction and/or ring closure reaction The amount of solvent used can be 1-10 times the mass of the compound of formula IV.

In the preparation method of indanone compounds provided by the present invention, the acylation reaction is usually carried out under the condition that an acylating reagent exists, and the acylating reagent can usually be thionyl chloride and/oxalyl chloride, and the acylating reagent The molar ratio relative to the compound of formula IV is usually substantially equal or excessive, for example, the molar ratio of the thionyl chloride to the compound of formula IV may be 1-3:1. When the acylating agent is added to the reaction system, it is usually added gradually, for example, it may be added dropwise.

In the preparation method of indanone compounds provided by the present invention, the acylation reaction can usually be carried out at a temperature not higher than the boiling point of the solvent or from room temperature to the boiling point of the solvent, for example, the temperature of the acylation reaction can be 0-100°C. Those skilled in the art can suitably adjust the reaction time of the acylation reaction according to the reaction process, and the method for monitoring the reaction process should be known to those skilled in the art, such as analytical methods such as chromatography and nuclear magnetic resonance, specifically The reaction time can be, for example, 2-16 hours.

In the preparation method of indanone compounds provided by the present invention, the ring closure reaction is usually carried out in the presence of a Lewis acid, which can be, for example, aluminum trichloride, zinc chloride, iron trichloride, tetrachloride The combination of one or more of tin chloride, aluminum tribromide, etc., said aluminum trichloride is usually substantially equal or excessive in molar ratio relative to the compound of formula IV, for example, said aluminum trichloride The molar ratio to the compound of formula IV can be 1-3:1, or 1.2-2:1. During the ring closure reaction, usually the corresponding acid chloride compound obtained from the acylation reaction can be added gradually to the reaction system (the system may include aluminum trichloride and a solvent), for example, it can be added dropwise.

In the preparation method of indanone compounds provided by the present invention, the ring-closing reaction can usually be carried out at a temperature not higher than the boiling point of the solvent or from room temperature to the boiling point of the solvent, for example, the temperature of the ring-closing reaction can be 0-100°C. Those skilled in the art can suitably adjust the reaction time of the ring-closing reaction according to the reaction process, and the method for monitoring the reaction process should be known to those skilled in the art, such as analytical methods such as chromatography and nuclear magnetic resonance, specifically The reaction time can be, for example, 2-16 hours.

In the preparation method of the indanone compounds provided by the present invention, those skilled in the art can select a suitable post-treatment method to post-process the product obtained from the ring-closing reaction. For example, after the reaction is finished, the post-treatment of the ring-closing reaction can be The steps include: quenching, liquid separation, organic phase desolvation and purification to obtain the indanone compound. Usually, acid or their aqueous solution can be added to the system for quenching. For example, the acid used can be HCl, and the corresponding aqueous solution can be, for example, hydrochloric acid. Those skilled in the art can choose an appropriate method to purify the precipitated product, for example, the purification method can be rectification, recrystallization and the like.

Compared with the prior art, the preparation method of the indenone compounds provided by the present invention has the advantages of low raw material cost, simple and convenient operation, less waste, and high yield, and is more suitable for industrial production. Compared with various indenones in the prior art The preparation method of ketone compounds has obvious advantages and has good industrialization prospects.

Embodiments of the present invention are described below through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific implementation modes, and various modifications or changes can be made to the details in this specification based on different viewpoints and applications without departing from the spirit of the present invention.

It should be noted that the process equipment or devices not specifically indicated in the following examples all adopt conventional equipment or devices in the art.

In addition, it should be understood that one or more method steps mentioned in the present invention do not exclude that there may be other method steps before and after the combined steps or other method steps may be inserted between these explicitly mentioned steps, unless otherwise There are descriptions; it should also be understood that the combined connection relationship between one or more devices/devices mentioned in the present invention does not exclude that there may be other devices/devices before and after the combined devices/devices or those explicitly mentioned Other devices/apparatus can also be interposed between the two devices/apparatus, unless otherwise stated. Moreover, unless otherwise stated, the numbering of each method step is only a convenient tool for identifying each method step, and is not intended to limit the sequence of each method step or limit the scope of the present invention. The change or adjustment of its relative relationship is in In the case of no substantive change in the technical content, it shall also be regarded as the applicable scope of the present invention.

Example 1

Preparation of 2-methyl-1-indanone:

A. In a 2L four-necked flask, add 102.1g (1.0mol) of ethyl propionate and 200g of tetrahydrofuran, and 102.0g (1.5mol) of fresh sodium ethoxide solid at room temperature. After the addition, the internal temperature rises to 50-60°C. Keep stirring for 2 hours; then start to add 190.0g (1.5mol) of benzyl chloride dropwise at 55-60°C, drop it within 2 hours, keep stirring for 1 hour, the GC central control shows that the end point is reached, and slowly add the reaction solution dropwise into 500g of water to carry out Quenching, the reaction solution is directly used for the next step reaction;

B. Pour the reaction solution in step A into a 2L four-neck flask, add 60.0g of sodium hydroxide solid, stir to dissolve it, heat it up to 60-65°C and keep it warm for about 3 hours. The GC central control shows that the end point is reached, and then cool down to 20 ℃, stand still for liquid separation, add 190.1 g of 30% HCl aqueous solution to the separated aqueous phase to adjust the pH to about 3.0, stand for separation, collect the organic phase, and then dry the organic phase with anhydrous sodium sulfate to obtain 136.3 g, yield 83.1 %(A, B two-step reaction);

C. Add 200g of dichloromethane to 136.3g of the organic phase obtained in step B, and then add 148.1g of thionyl chloride (1.24mol) dropwise at 35-40°C. At the end point, the concentrated solution of the acid chloride is obtained by desolventization; take another reaction bottle, add 166.1g of aluminum trichloride (1.24mol) and 300g of dichloromethane respectively, and the internal temperature drops to 0°C, then add the concentrated solution of the acid chloride dropwise, within 3h After dripping, the internal temperature is controlled at 0-10°C. The GC central control shows that the end point is reached. Add 200g of 5% HCl aqueous solution dropwise to quench the reaction, let it stand for liquid separation, and the separated organic layer is desolventized and rectified to obtain a light yellow color. Liquid 117.9g, GC purity 98.7%, yield 95.8%. ¹ H NMR (300MHz, CDCl ₃ ): δ=1.25-1.27(d, 3H), δ=2.54-2.76(d, 2H), δ=3.34-3.46(m, 1H), δ=7.31-7.40(t , 1H), δ=7.43-7.48(t, 1H), δ=7.51-7.60(t, 1H), δ=7.76-7.83(t, 1H).

Example 2

Preparation of 2,6-dimethyl-1-indanone:

A. In a 2L four-necked flask, add 88.1g (1.0mol) of methyl propionate and 200g of tetrahydrofuran, and 81.0g (1.5mol) of fresh sodium methoxide solid at room temperature. After the addition, the internal temperature rises to 50-60°C. Keep stirring for 2 hours; then start to add 182.8g (1.3mol) of p-methylbenzyl chloride dropwise at 55-60°C, drop it within 2 hours, keep stirring for 1 hour, the GC central control shows that the end point is reached, and slowly add the reaction solution dropwise to Quenching was carried out in 500g of water, and the reaction solution was directly used for the next step reaction;

B. Pour the reaction solution in step A into a 2L four-neck flask, add 60.0g of sodium hydroxide solid, stir to dissolve it, heat it up to 60-65°C and keep it warm for about 3 hours. The GC central control shows that the end point is reached, and then cool down to 20 ℃, stand still for liquid separation, add 190.1 g of 30% HCl aqueous solution to the separated aqueous phase to adjust the pH to about 3.0, stand for separation, collect the organic phase, and then dry the organic phase with anhydrous sodium sulfate to obtain 142.7 g, yield 80.1 %;

C. Add 200g of dichloromethane to 142.7g of the organic phase obtained in step B, and then add 150.1g (1.26mol) of thionyl chloride dropwise at 35-40°C. At the end point, the concentrated solution of the acid chloride is obtained by desolventization; take another reaction bottle, add 172.1g (1.29mol) of aluminum trichloride and 300g of dichloromethane respectively, and the internal temperature drops to 0°C, then add the concentrated solution of the acid chloride dropwise, within 3h After dropping, the internal temperature is controlled at 0-10°C. The GC central control shows that the end point is reached. Add 200g of 5% HCl aqueous solution dropwise to quench the reaction, let stand to separate the liquid, and the separated organic layer is desolvated and rectified to obtain a golden yellow color. Liquid 122.6g, GC purity 99.0%, yield 94.6%. ¹ H NMR (300MHz, CDCl ₃ ): δ=1.25-1.27(d, 3H), δ=2.35(s, 3H), δ=2.59-2.69(m, 2H), δ=3.26-3.35(m, 1H ), δ=7.29-7.38 (m, 2H), δ=7.50 (s, 1H), GC/MS (m/z=160).

Example 3

Preparation of 2-methyl-6-fluoro-1-indanone:

A. In a 2L four-necked flask, add 88.1g of methyl propionate (1.0mol) and 200g of tetrahydrofuran, and 54.0g of fresh sodium hydride (2.25mol) solid at room temperature. After the addition, the internal temperature rises to 40-50°C. Insulate and stir for 2 hours; then start to drop 202.4g (1.4mol) of p-fluorobenzyl chloride at 55-60°C, drop it within 2 hours, keep stirring for 1 hour, the GC central control shows that the end point is reached, and slowly add the reaction solution to 500g quenched in water, and the reaction solution was directly used for the next reaction;

B. Pour the reaction solution in step A into a 2L four-neck flask, add 75.0g of potassium hydroxide solid, stir to dissolve it, heat up to 60-65°C and keep it warm for about 3 hours. The GC central control shows that the end point is reached, and then cool down to 20°C. ℃, stand still for liquid separation, add 202.1 g of 30% HCl aqueous solution to the separated aqueous phase to adjust the pH to about 3.0, stand for separation, collect the organic phase, and then dry the organic phase with anhydrous sodium sulfate to obtain 141.8 g, yield 77.8 %;

C. Add 200g of dichloromethane to 141.8g of the organic phase obtained in step B, then add 146.5g of thionyl chloride dropwise at 35-40°C, keep warm for 1h after dropping, the GC central control shows that the end point is reached, and the solution is removed Obtain the concentrated solution of acid chloride; take another reaction bottle, add 172.1g of aluminum trichloride and 300g of dichloromethane respectively, the internal temperature drops to 0°C, then add the concentrated solution of acid chloride dropwise, the dripping is completed within 3 hours, and the internal temperature is controlled at 0 -10°C, the GC central control shows that the end point is reached, dropwise add 200g of 5% HCl aqueous solution to quench the reaction, let stand to separate the liquid, the separated organic layer is desolvated, add 100g of ethanol to dissolve, cool to -20°C and precipitate off-white The solid weighed 123.1 g after drying, the GC purity was 99.1%, and the yield was 95.5%. ¹ H NMR (300MHz, CDCl ₃ ): δ=1.25-1.27(d, 3H), δ=2.55-2.77(d, 2H), δ=3.33-3.46(m, 1H), δ=7.05-7.25(m , 2H), δ=7.51-7.65 (d, 1H).

Example 4

Preparation of 6-methyl-1-indanone:

A. In a 2L four-neck flask, add 88.1g ethyl acetate, 200g tetrahydrofuran, and 102.0g fresh sodium ethoxide solid at room temperature. After the addition, the internal temperature rises to 50-60°C, keep stirring for 2 hours; then start to control the 55- Add 182.8g of p-methylbenzyl chloride dropwise at 60°C, finish the drop within 2 hours, keep stirring for 1 hour, the GC central control shows that the end point is reached, slowly add the reaction solution to 500g of water to quench, and the reaction solution is directly used in the next step reaction;

B. Pour the reaction solution in step A into a 2L four-neck flask, add 60.0g of sodium hydroxide solid, stir to dissolve it, heat it up to 60-65°C and keep it warm for about 3 hours. The GC central control shows that the end point is reached, and then cool down to 20 ℃, stand still for liquid separation, add 190.1 g of 30% HCl aqueous solution to the separated aqueous phase to adjust the pH to about 3.0, stand for separation, collect the organic phase, and then dry the organic phase with anhydrous sodium sulfate to obtain 137.8 g, yield 83.9 %;

C. Add 200g of dichloromethane to 137.8g of the organic phase obtained in step B, and then add 160.1g of oxalyl chloride dropwise at 35-40°C, keep it warm for 1h after dropping, the GC central control shows that the end point is reached, and the acid chloride is obtained by precipitation Concentrate solution; Take another reaction bottle, add 172.1g aluminum trichloride and 300g dichloromethane respectively, the internal temperature drops to 0°C, then add acid chloride concentrated solution dropwise, drop it within 3h, and control the internal temperature at 0-10 ℃, the GC central control shows that the end point is reached, and the reaction is quenched by adding 200g of 5% HCl aqueous solution dropwise, and the liquid is separated. The separated organic layer is precipitated and rectified to obtain 117.6g of a light yellow liquid with a melting point of 60-62°C. The purity is 99.2%, and the yield is 95.1%. ¹ H NMR (300MHz, CDCl ₃ ): δ=2.40(s, 3H), δ=2.62-2.69(m, 2H), δ=3.05-3.15(m, 2H), δ=7.25-7.36(m, 2H ), δ=7.55(s, 1H).

Example 5

Preparation of 5-chloro-1-indanone:

A. In a 2L four-neck flask, add 88.1g ethyl acetate, 204.2g tetrahydrofuran, and 102.0g fresh sodium ethoxide solid at room temperature. After the addition, the internal temperature rises to 50-60°C, keep stirring for 2 hours; then start to control 55 Add 225.4g of m-chlorobenzyl chloride dropwise at -60°C, finish the drop within 2 hours, keep stirring for 1 hour, the GC central control shows that the end point is reached, slowly add the reaction solution to 500g of water to quench, and the reaction solution is directly used in the next step reaction;

B. Pour the reaction solution in step A into a 2L four-neck flask, add 60.0g of sodium hydroxide solid, stir to dissolve it, heat it up to 60-65°C and keep it warm for about 3 hours. The GC central control shows that the end point is reached, and then cool down to 20 ℃, stand still for liquid separation, add 190.1 g of 30% HCl aqueous solution to the separated aqueous phase to adjust the pH to about 3.0, stand for separation, collect the organic phase, then dry the organic phase with anhydrous sodium sulfate to obtain 143.2 g, yield 77.6 %;

C. Add 200g of dichloromethane to 143.2g of the organic phase obtained in step B, then add 150.1g of thionyl chloride dropwise at 35-40°C, and keep warm for 1h after the drop is completed. Obtain the concentrated solution of acid chloride; take another reaction bottle, add 172.1g of aluminum trichloride and 300g of dichloromethane respectively, the internal temperature drops to 0°C, then add the concentrated solution of acid chloride dropwise, the dripping is completed within 3 hours, and the internal temperature is controlled at 0 -10°C, the GC central control shows that it has reached the end point, dropwise add 200g of 5% HCl aqueous solution to quench the reaction, let it stand for liquid separation, the separated organic layer is desolvated, add 100g of ethanol to dissolve, then cool to -20°C to precipitate a yellow solid , solid-liquid separation, dry weighing 121.5g, purity 98.5%, melting point 91.5-96°C, yield 92.6%. ¹ H NMR (300MHz, CDCl ₃ ): δ=2.66-2.71(m, 2H), δ=2.95-3.09(m, 2H), δ=7.14-7.26(m, 2H), δ=7.75-7.80(d , 1H).

To sum up, the present invention effectively overcomes various shortcomings in the prior art and has high industrial application value.

The above-mentioned embodiments only illustrate the principles and effects of the present invention, but are not intended to limit the present invention. Anyone skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those skilled in the art without departing from the spirit and technical ideas disclosed in the present invention should still be covered by the claims of the present invention.

Claims (10)

1. A preparation method of indanone compound, comprising: 1) Condensing the compound of formula I with the compound of formula II to prepare the compound of formula III; 2) hydrolyzing the compound of formula III in the presence of a base to prepare the compound of formula IV; 3) Acylate and ring-close the compound of formula IV to prepare the compound of formula V; The structural formula of the compound of formula I-V is as follows: Wherein, R1, R2, R3, R4 are each independently selected from H, Cl, Br, I, F, straight chain or branched C1-C18 alkyl; R5 is selected from H, Cl, Br, straight chain or branched C1-C18 alkyl; R6 is selected from linear or branched C1-C18 alkyl; X is selected from Cl or Br. 2. the preparation method of a kind of indanone compound as claimed in claim 1, is characterized in that, also comprises one or more in the following technical characteristics: A1) R1, R2, R3, R4 are each independently selected from H, Cl, Br, F, linear or branched C1-C8 alkyl; A2) R5 is selected from linear or branched C1-C10 alkyl; A3) R6 is selected from linear or branched C1-C8 alkyl groups. 3. the preparation method of a kind of indanone compound as claimed in claim 2, is characterized in that, also comprises one or more in the following technical characteristics: B1) R1, R2, R3, R4 are each independently selected from H, Cl, linear or branched C1-C4 alkyl; B2) R5 is selected from linear or branched C1-C4 alkyl; B3) R6 is selected from linear or branched C1-C4 alkyl groups. 4. the preparation method of a kind of indanone compound as claimed in claim 1, is characterized in that, also comprises one or more in the following technical characteristics: C1) In step 1), the molar ratio of the compound of formula I to the compound of formula II is 1-6:1; C2) In step 1), the reaction is carried out in the presence of a base, and the molar ratio of the base to the compound of formula II is 1 to 5:1; C3) In step 1), the reaction is carried out in the presence of a solvent; C4) In step 1), the reaction temperature is 0-120°C; In step 1) of C5), the post-treatment of the reaction includes: adding water to quench. 5. the preparation method of a kind of indanone compound as claimed in claim 4, is characterized in that, also comprises one or more in the following technical characteristics: D1) In step 1), the molar ratio of the compound of formula I to the compound of formula II is 1-3:1; D2) In step 1), the base is selected from one or more combinations of alkali metal organic salts, alkali metal carbonates, sodium amide or sodium hydride; D3) In the step 1), the molar ratio of the base to the compound of formula II is 1-3:1; D4) In the step 1), the solvent is selected from organic solvents, the organic solvent is preferably selected from ether solvents, and the organic solvent is preferably selected from diethyl ether, methyl tert-butyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran one or a combination of them; D5) In step 1), the reaction temperature is 20-50°C. 6. the preparation method of a kind of indanone compound as claimed in claim 5 is characterized in that, in described step 1), described alkali is selected from sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, tert-butanol A combination of one or more of sodium, potassium tert-butoxide, n-butyllithium, LDA, sodium hydride, sodium amide, sodium carbonate, and potassium carbonate. 7. the preparation method of a kind of indanone compound as claimed in claim 1, is characterized in that, also comprises one or more in the following technical characteristics: E1) In step 2), the base is selected from NaOH and/or KOH; E2) In step 2), the molar ratio of the base to the compound of formula III is 1 to 6:1; E3) In the step 2), the reaction temperature is 0-100°C; In step 2) of E4), the post-treatment of the reaction includes: liquid separation, adjusting the pH of the obtained aqueous phase to 2.0-5.0, and collecting the organic phase. 8. the preparation method of a kind of indanone compound as claimed in claim 7, is characterized in that, also comprises one or more in the following technical characteristics: In step 2) of F1), the molar ratio of the base to the compound of formula III is 1 to 3:1; In step 2) of F2), the reaction temperature is 30-60°C. 9. the preparation method of a kind of indanone compound as claimed in claim 1, is characterized in that, also comprises one or more in the following technical characteristics: G1) In the step 3), the reaction is carried out in the presence of a solvent, and the solvent is selected from an organic solvent; G2) In step 3), the acylation reaction is carried out in the presence of an acylating reagent, and the molar ratio of the acylating reagent to the compound of formula IV is 1 to 3:1; G3) In the step 3), the reaction temperature of the acylation reaction is 0-100°C; G4) In the step 3), the ring-closing reaction is carried out in the presence of a Lewis acid; G5) In the step 3), the reaction temperature of the ring closure reaction is 0-100°C; In step 3) of G6), the post-treatment of the reaction includes: quenching, liquid separation, organic phase precipitation, and purification to obtain the indanone compound. 10. the preparation method of a kind of indanone compound as claimed in claim 9, is characterized in that, also comprises one or more in the following technical characteristics: H1) In step 3), the organic solvent is selected from one or more combinations of dichloromethane, dichloroethane, toluene, chlorobenzene, nitromethane, and nitroethane; H2) In step 3), the acylating agent is selected from thionyl chloride and/or oxalyl chloride; H3) In step 3), the Lewis acid is selected from one or more combinations of aluminum trichloride, zinc chloride, ferric chloride, tin tetrachloride, and aluminum tribromide; H4) In step 3), the molar ratio of the Lewis acid to the compound of formula IV is 1-3:1, preferably 1.2-2:1; In step 3) of H5), the method of purification is rectification and/or recrystallization.