A method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone

Abstract

The invention discloses a method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone, wherein p-methylbenzaldehyde and 2-(triphenylphosphine) propionic acid are subjected to Wittig reaction to construct a double bond, thereby obtaining 2-methyl-3-(4-methylphenyl)-2-acrylic acid, and then 2-methyl-3-(4-methylphenyl)-2-acrylic acid is subjected to hydrogenation, chlorination, and Friedel-Crafts acyl cyclization to synthesize 2,6-dimethyl-2,3-dihydro-1-indanone. The invention has a short synthesis route, mild reaction conditions, high total yield, unique double bond position, and no rearrangement, and has good industrial application value.

Description

Technical Field

[0001] The invention belongs to the field of compound synthesis, and specifically relates to a method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone. Background Art

[0002] 2,6-Dimethyl-1-indanone is an important raw material for triazine indole. Triazine indole, with the chemical name N-[(lR, 2S)-2,3-dihydro-2,6-dimethyl-lH-inden-l-yl]-6-[(lRS)-l-fluoroethyl]-l,3,5-triazine-2,4-diamine, is a triazine herbicide developed by Bayer AG of Germany. It is mainly used to control annual weeds (such as crabgrass, goosegrass, bluegrass, etc.) and 65 other grass weeds and broadleaf weeds in lawns, flowers and vegetation. It has the advantages of broad-spectrum anti-weed, long-lasting efficacy, low dosage and environmental protection.

[0003] Through literature research, the currently reported synthetic methods for preparing indanone compounds mainly include: 1. Synthesis method using benzaldehyde as raw material: Substituted benzaldehyde is used as a raw material, and substituted malonate is reacted with substituted malonate to obtain 3-substituted phenyl-2-substituted acrylic acid, which is then hydrogenated, chlorinated, and cyclized with aluminum trichloride or polyphosphoric acid to synthesize indanone compounds (Organometallics 2006, 25, 1217-1229).

[0004] Using substituted benzaldehyde as raw material, it first undergoes a Perkin reaction with anhydride, followed by hydrogenation, chlorination, and aluminum chloride Friedel-Crafts cyclization to synthesize indanone compounds (European Journal of Medicinal Chemistry, 2013, 62, 632-648).

[0005] 2. Using substituted aromatic hydrocarbons as raw materials: The method uses substituted aromatic hydrocarbon as raw material, reacts with 2-substituted propionyl chloride in the presence of aluminum trichloride as a catalyst to generate substituted phenyl ethyl ketone, and then brominates, undergoes aluminum trichloride-catalyzed cyclization, and hydrolyzes to obtain indanone compounds (US2002077507).

[0006] 3. Using substituted benzyl halides as raw materials: The method mainly uses substituted benzyl halides such as benzyl chloride as raw materials for synthesis. The benzyl halide reacts with substituted malonate to generate substituted phenylpropionic acid compounds, which are then chlorinated and catalyzed by aluminum chloride or phosphoric acid-containing compounds to further synthesize indanone compounds (US2007 / 0135595 A1).

[0007] In the method provided in the above literature, the raw material cost is high, the reaction route is long, the operation is complicated, and the purity of the produced 2,6-dimethyl-2,3-dihydro-1-indanone is not high. The reactants cannot be reacted completely, resulting in waste. Moreover, the yield of 2,6-dimethyl-2,3-dihydro-1-indanone in the synthesis process is not high. Summary of the invention

[0008] In view of the above deficiencies in the prior art, the present invention provides a method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone, which has a short synthesis route, mild reaction conditions, a unique double bond position, no rearrangement, and a high total yield.

[0009] The structural formula of 2,6-dimethyl-2,3-dihydro-1-indanone synthesized by the present invention is as follows: The method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone of the present invention comprises the following steps: (A) Wittig reaction: p-Tolualdehyde shown in Formula I and Wittig reagent 2-(triphenylphosphine)propionic acid shown in Formula II undergo Wittig reaction to obtain the intermediate (2-methyl-3-(4-methylphenyl)-2-propenoic acid) shown in Formula III; (B) Hydrogenation reaction: The intermediate represented by formula III reacts with hydrogen under the catalytic action of a catalyst to obtain the intermediate represented by formula IV; (C) Acylation reaction: the intermediate represented by formula IV undergoes an acylation reaction with an acylating agent to obtain the intermediate represented by formula V; (D) Friedel-Crafts acylation reaction: The intermediate shown in Formula V undergoes Friedel-Crafts acylation reaction under the action of Lewis acid to obtain 2,6-dimethyl-2,3-dihydro-1-indanone product; Furthermore, in step (A), the molar ratio of p-tolualdehyde to Wittig reagent 2-(triphenylphosphine)propionic acid is 1:1.03-1.5, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50.

[0010] Furthermore, in step (A), the preparation method of the Wittig reagent 2-(triphenylphosphine) propionic acid is: triphenylphosphine and 2-chloropropionic acid are reacted in a solvent to generate a quaternary phosphonium salt, and then reacted at low temperature and under the action of a strong base to generate a stable phosphine ylide, and finally the pH value is adjusted to acidic to generate 2-(triphenylphosphine) propionic acid).

[0011] Wherein, the molar ratio of triphenylphosphine to 2-chloropropionic acid is 1.03-1.5:1, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5.

[0012] The solvent used may be at least one of ether, THF, toluene, methyl tert-butyl ether and the like.

[0013] The reaction temperature of triphenylphosphine and 2-chloropropionic acid is 40-90°C, for example, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, and the reaction time is 20-24h.

[0014] When the quaternary phosphonium salt forms a phosphine ylide, the temperature is less than -30°C, such as -31°C, -35°C, -40°C, -45°C, -50°C, and any range of values ​​therebetween. The pH of the system is adjusted to be greater than 13, such as 13.1, 13.5, 14, 15, 16, etc., and any range of values ​​therebetween, by using alkaline substances such as NaOH, KOH, sodium methoxide, and n-butyl lithium. The reaction time is 1 to 2 hours.

[0015] Among them, the acidic pH range is 2~4, and the pH adjustment can be achieved by hydrochloric acid. After adjusting to acidity, the reaction is carried out for 1~2 hours to obtain the final 2-(triphenylphosphine ylidene) propionic acid) product.

[0016] Furthermore, in step (A), the Wittig reaction is carried out in a solvent; the solvent includes, but is not limited to, at least one of an aromatic hydrocarbon solvent, an ether solvent, etc. For example, the solvent is at least one of toluene, xylene, tetrahydrofuran (THF), ether, ethylene glycol dimethyl ether, methyl tert-butyl ether (MTBE), etc. The solvent is used as a reaction medium, and its amount can be adjusted according to actual needs.

[0017] Furthermore, in step (A), the raw materials and the solvent can be mixed in any order. The raw materials and the solvent can be mixed together, or the solvent can be mixed with one raw material first and then added to the other raw material, or the two raw materials can be mixed with the solvent separately and then the raw material solutions can be mixed.

[0018] Preferably, 2-(triphenylphosphinoylidene)propionic acid and a solvent are first mixed, and then a mixture of p-tolualdehyde and the solvent is added thereto.

[0019] Preferably, the mixture of p-tolualdehyde and the solvent is added slowly, more preferably added dropwise.

[0020] Preferably, the mixing temperature of the raw materials is controlled to be -10°C to -5°C, for example, -10°C, -9°C, -8°C, -7°C, -6°C, -5°C.

[0021] Furthermore, in step (A), after the raw materials are mixed, the reaction is carried out at 0-40°C, for example, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, and the reaction time is 8-10h.

[0022] Furthermore, in step (A), after the reaction, the insoluble matter is filtered out, and then the solvent is recovered by distillation, reduced pressure distillation, etc. to obtain the intermediate represented by formula III.

[0023] Furthermore, in step (B), the intermediate represented by formula III is hydrogenated with hydrogen in the presence of a catalyst to obtain the intermediate represented by formula IV; the catalyst is a catalyst commonly used in catalytic hydrogenation reactions, including but not limited to palladium carbon, platinum carbon, Raney nickel, etc. The amount of the catalyst used is 6-10wt% of the mass of the intermediate represented by formula III.

[0024] Furthermore, in step (B), the reaction is carried out in the presence of a solvent, and the solvent includes but is not limited to at least one of an alcohol solvent, a benzene solvent, an ether solvent, etc.; for example, the solvent is at least one of methanol, ethanol, toluene, tetrahydrofuran, dioxane, etc. The amount of the solvent used as a reaction medium can be adjusted according to actual needs.

[0025] Furthermore, in step (B), the reaction is carried out in a high-pressure reactor, and the pressure of hydrogen in the system is 0.2-0.5 MPa.

[0026] Furthermore, in step (B), the reaction is carried out at 20-30° C., such as 20° C., 25° C., or 30° C. The reaction time is 6-8 h.

[0027] Furthermore, in step (B), after the reaction, the solvent is recovered by distillation, reduced pressure distillation, etc. to obtain an intermediate represented by formula IV.

[0028] Further, in step (C), the acylating agent is selected from dithionyl chloride or oxalyl chloride; the molar ratio of the intermediate represented by formula IV to the acylating agent is 1:1.03-2.0, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0.

[0029] Furthermore, in step (C), the reaction is carried out in the presence of a solvent, and the solvent is selected from an organic solvent, preferably a combination of one or more of dichloromethane, dichloroethane, toluene, etc. The amount of the solvent used as a reaction medium can be adjusted according to actual needs.

[0030] Furthermore, in step (C), there is no special requirement for the order of adding the raw materials. The reaction is carried out at 20-30°C, for example, 20°C, 25°C, 30°C. The reaction time is 3-4h.

[0031] Furthermore, in step (C), after the reaction, a reaction solution containing an intermediate represented by formula V is obtained, and the reaction solution can be directly used in the next step without the need to extract and separate the intermediate.

[0032] Furthermore, in step (D), the Friedel-Crafts acyl ring-closing reaction is carried out in the presence of a Lewis acid, and the Lewis acid is selected from a combination of one or more of aluminum chloride, zinc chloride, ferric chloride, tin tetrachloride, and aluminum bromide.

[0033] Further, in step (D), the molar ratio of the intermediate represented by formula V to the Lewis acid is 1:1.03-2.0, for example, 1:1.03, 1:1.05, 1:1.1, 1:1.15, 1:1.20, 1:1.25, 1:1.30, 1:1.35, 1:1.40, 1:1.45, 1:1.50, 1:1.55, 1:1.60, 1:1.65, 1:1.70, 1:1.75, 1:1.80, 1:1.85, 1:1.90, 1:1.95, 1:2.0.

[0034] Furthermore, in step (D), the reaction is carried out in the presence of a solvent, the solvent is selected from an organic solvent, preferably a combination of one or more of dichloromethane, dichloroethane, toluene, etc. The agent is used as the reaction medium, and its amount can be adjusted according to actual needs.

[0035] Furthermore, in step (D), preferably, the reaction solution obtained in step (C) is dropped into a mixture of Lewis acid and solvent.

[0036] Furthermore, in step (D), the mixing temperature of the raw materials and the reaction temperature are both 20-30° C., such as 20° C., 25° C., 30° C. The reaction time is 3-4 hours.

[0037] Furthermore, in step (D), after the reaction is completed, the reaction solution is filtered to remove insoluble matter, and then the solvent is recovered by distillation, reduced pressure distillation, etc. to obtain the final product - 2,6-dimethyl-2,3-dihydro-1-indanone.

[0038] Compared with the prior art, the present invention has the following advantages: 1. The present invention provides a new route for the synthesis of 2,6-dimethyl-2,3-dihydro-1-indanone. The reaction requires the preparation of a Wittig reagent (phosphorus ylide) first, and then the double bond is constructed by the Wittig reaction, thereby avoiding the high temperature conditions of the Perkin reaction, and the reaction conditions are mild, the synthesis method is simple, and the synthesis route is short.

[0039] 2. The present invention uses the Wittig reaction for the first time to synthesize intermediate III, which has the advantages of high yield, unique double bond position, no rearrangement, etc., thereby improving the reaction yield.

[0040] 3. When aluminum chloride is used as the Lewis acid in the present invention, the aluminum-containing wastewater generated during the reaction can be used to make flocculants. The overall route is clean and environmentally friendly, has little pollution to the environment, and is suitable for industrial production.

[0041] 4. The present invention improves the yield and purity of the product and has good industrial practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is the hydrogen spectrum of 2,6-dimethyl-2,3-dihydro-1-indanone synthesized in Example 1.

[0043] Figure 2 This is the carbon spectrum of 2,6-dimethyl-2,3-dihydro-1-indanone synthesized in Example 1. DETAILED DESCRIPTION

[0044] The present invention is further described below in conjunction with specific embodiments. The following description is only exemplary and does not limit the scope of protection. Other implementation schemes obtained by those skilled in the art without creative work without departing from the inventive concept of the present invention are also within the scope of protection.

[0045] In the following examples, unless otherwise specified, all raw materials used are commercially available products.

[0046] In the following examples, unless otherwise specified, the concentrations are all mass percentage concentrations.

[0047] In the following examples, yield = actual mass of product × purity / theoretical mass of product.

[0048] In the following examples, 2-(triphenylphosphine) propionic acid is prepared by the following method: 63.59g of triphenylphosphine and 21.92g of 2-chloropropionic acid are added to 87.69g of tetrahydrofuran solvent, stirred evenly, heated to 60°C for 24h to generate quaternary phosphonium salt, cooled to -35°C, sodium hydroxide is added to the reaction solution until the pH is 13-14, reacted for 2-3h, then hydrochloric acid is added to adjust the pH to 2-3, reacted for 1-2h, and insoluble matter is filtered out after the reaction to obtain a tetrahydrofuran solution of 2-(triphenylphosphine) propionic acid. The tetrahydrofuran solution of 2-(triphenylphosphine) propionic acid can be directly used in the Wittig reaction, or the solvent can be recovered to obtain 2-(triphenylphosphine) propionic acid and then used in the Wittig reaction.

[0049] Example 1 Wittig reaction: At -10°C, add 80.24 g (0.120 mol) of a 50% tetrahydrofuran solution of 2-(triphenylphosphine) propionic acid into a four-necked flask, and then slowly add a mixed solution of 12.39 g (0.100 mol) of 97% p-tolualdehyde and 24.77 g of tetrahydrofuran into the four-necked flask. After the addition, heat the mixture to 0°C and stir to react for 8 hours. After the reaction, filter the mixture, and then vacuum concentrate the filtrate to recover tetrahydrofuran to obtain a crude compound III (18.20 g, HPLC purity 87.0%) with a yield of 90% based on p-tolualdehyde.

[0050] Hydrogenation reaction: Add 18.20 g (0.090 mol) of crude compound III, 100.0 g of methanol, and 1.18 g of palladium carbon to the autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at room temperature for 6 hours. After the reaction, the filtrate was filtered, and the filtrate was vacuum concentrated to recover methanol to obtain crude compound IV (17.88 g, HPLC purity of 86.0%), with a yield of 96.0% based on compound III.

[0051] Acylation-cyclization reaction: At room temperature, add 17.88g (0.086mol) of crude compound IV, 35.76g of dichloromethane, and 20.97g (0.173mol) of 98% thionyl chloride to a four-necked bottle, stir and react for 3h at room temperature to obtain a dichloromethane solution of compound V. Add the dichloromethane solution of compound V dropwise into 48.53g of a dichloromethane solution containing 14.25g (0.104mol) of 97% aluminum trichloride. After the addition is complete, react at room temperature for 3 hours, filter the reaction if qualified, and vacuum concentrate to recover dichloromethane to obtain a crude product of 2,6-dimethyl-2,3-dihydro-1-indanone (14.96g, HPLC purity of 85%), with a yield of 92% based on compound IV and a four-step yield of 79.5% based on p-methylbenzaldehyde.

[0052] The structural formula of the synthesized product 2,6-dimethyl-2,3-dihydro-1-indanone is: The NMR information of the product is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.54 – 7.49 (m 1H), 7.40 – 7.34 (m, 1H), 7.32 – 7.26 (m, 1H), 3.37 – 3.26 (m, 1H), 2.71 – 2.59 (m, 2H), 2.38 – 2.34(m, 3H), 1.30 – 1.22 (m, 3H). 13 C NMR (101 MHz, CDCl3) δ 209.5, 150.8, 137.3, 136.5, 136.0, 126.2, 42.3, 34.6, 21.1, 16.4. Example 2 Wittig reaction: 80.24 g (0.120 mol) of a 50% toluene solution of 2-(triphenylphosphine)propionic acid was added to a four-necked flask at -10°C, and then a mixed solution of 12.39 g (0.100 mol) of 97% p-tolualdehyde and 24.77 g of toluene was slowly added to the four-necked flask. The temperature was raised to 0°C and stirred for reaction for 8 hours. After the reaction, the filtrate was filtered and the toluene was recovered by vacuum concentration to obtain a crude compound III (18.00 g, HPLC purity of 86.0%), with a yield of 88% based on p-tolualdehyde.

[0053] Hydrogenation reaction: Add 18.00 g (0.088 mol) of crude compound III, 100.0 g of methanol, and 1.18 g of palladium carbon to the autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at room temperature for 6 hours. After the reaction, the filtrate was filtered and the filtrate was vacuum concentrated to recover methanol to obtain a crude compound IV (17.57 g, HPLC purity of 85.6%), with a yield of 96.0% based on compound III.

[0054] Acid chlorination-cyclization reaction: At room temperature, add 17.57g (0.084mol) of crude compound IV, 35.13g of dichloromethane, and 20.51g (0.169mol) of 98% dichlorothionyl in a four-necked bottle, stir and react at room temperature for 3h. After the reaction is qualified, a dichloromethane solution of compound V is obtained. The dichloromethane solution of compound V is dropped into 47.45g of dichloromethane solution containing 13.94g (0.101mol) of 97% aluminum trichloride. After the addition is completed, react at room temperature for 3 hours. After the reaction is qualified, filter, and vacuum concentrate the filtrate to recover dichloromethane to obtain a crude product of 2,6-dimethyl-2,3-dihydro-1-indanone (14.70g, HPLC purity of 84.6%), with a yield of 92% based on compound IV and a four-step yield of 77.7% based on p-methylbenzaldehyde.

[0055] Example 3 Wittig reaction: At -10°C, add 80.24 g (0.120 mol) of a 50% tetrahydrofuran solution of 2-(triphenylphosphine) propionic acid into a four-necked flask, and then slowly add a mixed solution of 12.39 g (0.100 mol) of 97% p-tolualdehyde and 24.77 g of tetrahydrofuran into the four-necked flask. After the addition, heat to 40°C and stir to react for 8 hours. After the reaction, filter, and then vacuum concentrate the filtrate to recover tetrahydrofuran to obtain a crude compound III (16.28 g, HPLC purity 74.0%), with a yield of 68% based on p-tolualdehyde.

[0056] Hydrogenation reaction: Add 16.28 g (0.068 mol) of crude compound III, 100.0 g of methanol, and 1.18 g of palladium carbon to the autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at room temperature for 6 hours. After the reaction, the filtrate was filtered, and the filtrate was vacuum concentrated to recover methanol to obtain a crude compound IV (16.14 g, HPLC purity of 71.0%), with a yield of 94% based on compound III.

[0057] Acid chlorination-cyclization reaction: At room temperature, add 16.14g (0.064mol) of crude compound IV, 32.27g of dichloromethane, and 15.52g (0.128mol) of 98% dichlorothionyl in a four-necked bottle, stir and react at room temperature for 3h. After the reaction is qualified, a dichloromethane solution of compound V is obtained. The dichloromethane solution of compound V is dropped into 35.89g of dichloromethane solution containing 10.54g (0.077mol) of 97% aluminum trichloride. After the addition is complete, react at room temperature for 3 hours. After the reaction is qualified, filter, and vacuum concentrate the filtrate to recover dichloromethane to obtain a crude product of 2,6-dimethyl-2,3-dihydro-1-indanone (12.53g, HPLC purity of 73.0%), with a yield of 89% based on compound IV and a four-step yield of 56.9% based on p-methylbenzaldehyde.

[0058] Example 4 Wittig reaction: Same as Example 1.

[0059] Hydrogenation reaction: Add 18.20 g (0.090 mol) of crude compound III, 100.0 g of methanol, and 1.18 g of platinum carbon into the autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at room temperature for 6 h. After the reaction, the filtrate was filtered and the filtrate was vacuum concentrated to recover methanol to obtain crude compound IV (18.07 g, HPLC purity of 86.0%), with a yield of 97.0% based on compound III.

[0060] Acid chlorination-cyclization reaction: At room temperature, add 18.07g (0.087mol) of crude compound IV, 36.13g of dichloromethane, and 21.20g (0.175mol) of 98% dichlorothionyl to a four-necked bottle, stir and react for 3h at room temperature, and obtain a dichloromethane solution of compound V after the reaction is qualified. Add the dichloromethane solution of compound V dropwise into 49.04g of dichloromethane solution containing 14.40g (0.105mol) of 97% aluminum trichloride, react at room temperature for 3 hours after the addition is complete, filter after the reaction is qualified, and vacuum concentrate the filtrate to recover dichloromethane to obtain a crude product of 2,6-dimethyl-2,3-dihydro-1-indanone (15.11g, HPLC purity of 85%), with a yield of 92% based on compound IV and a four-step yield of 80.3% based on p-methylbenzaldehyde.

[0061] Example 5 Wittig reaction: Same as Example 1.

[0062] Hydrogenation reaction: 18.20 g (0.090 mol) of crude compound III, 100.0 g of methanol, and 1.18 g of Raney nickel were added to the autoclave. During the reaction, the hydrogen pressure was controlled at 0.2-0.5 MPa, and the reaction was stirred at room temperature for 6 h. After the reaction, the filtrate was filtered and the filtrate was vacuum concentrated to recover methanol to obtain crude compound IV (17.14 g, HPLC purity of 86.0%), with a yield of 92.0% based on compound III.

[0063] Acid chlorination-cyclization reaction: At room temperature, add 17.14g (0.083mol) of crude compound IV, 34.27g of dichloromethane, and 20.10g (0.166mol) of 98% dichlorothionyl in a four-necked bottle, stir and react at room temperature for 3h. The reaction is qualified to obtain a dichloromethane solution of compound V. The dichloromethane solution of compound V is dropped into 46.50g of dichloromethane solution containing 13.66g (0.099mol) of 97% aluminum trichloride. After the addition is completed, react at room temperature for 3 hours, filter after the reaction, and vacuum concentrate the filtrate to recover dichloromethane to obtain a crude product of 2,6-dimethyl-2,3-dihydro-1-indanone (14.34g, HPLC purity of 85%), with a yield of 92% based on compound IV and a four-step yield of 76.2% based on p-methylbenzaldehyde.

Claims

1. A method for synthesizing 2,6-dimethyl-2,3-dihydro-1-indanone, characterized in that The following steps are involved: (A) p-Tolualdehyde represented by Formula I reacts with 2-(triphenylphosphine)propionic acid represented by Formula II to obtain an intermediate represented by Formula III; (B) the intermediate represented by formula III reacts with hydrogen in the presence of a catalyst to produce the intermediate represented by formula IV; (C) the intermediate represented by formula IV undergoes acylation reaction with an acylating agent to obtain the intermediate represented by formula V; (D) The intermediate represented by formula V reacts under the action of Lewis acid to obtain 2,6-dimethyl-2,3-dihydro-1-indanone; 。 2. The synthesis method according to claim 1, characterized in that: In step (A), the molar ratio of p-tolualdehyde to 2-(triphenylphosphinoylidene)propionic acid is 1:1.03-1.

5.

3. The synthesis method according to claim 1 or 2, characterized in that: In step (A), the mixing temperature of the raw materials is -10°C to -5°C; after the raw materials are mixed, the reaction is carried out at 0-40°C.

4. The synthesis method according to claim 1, characterized in that: In step (B), the catalyst includes palladium carbon, platinum carbon or Raney nickel; preferably, the amount of the catalyst is 6-10% of the mass of the intermediate shown in formula III.

5. The synthesis method according to claim 1 or 4, characterized in that: In step (B), the pressure of hydrogen in the system is 0.2-0.5 MPa.

6. The synthesis method according to claim 1 or 4, characterized in that: In step (B), the reaction is carried out at 20-30°C.

7. The synthesis method according to claim 1, characterized in that: In step (C), the molar ratio of the intermediate represented by formula IV to the acylating agent is 1:1.03-2.0; preferably, the acylating agent is thionyl chloride or oxalyl chloride.

8. The synthesis method according to claim 1 or 7, characterized in that: In step (C), the reaction is carried out at 20-30°C; preferably, in step (D), the reaction temperature is 20-30°C.

9. The synthesis method according to claim 1, characterized in that: In step (D), the molar ratio of the intermediate represented by formula V to the Lewis acid is 1:1.03-2.0; preferably, the Lewis acid is at least one of aluminum trichloride, zinc chloride, ferric trichloride, tin tetrachloride, and aluminum tribromide.

10. The synthesis method according to claim 1, 2, 4, 7 or 9, characterized in that: Include at least one of the following conditions: Condition 1, the preparation method of Wittig reagent 2-(triphenylphosphine) propionic acid is: triphenylphosphine and 2-chloropropionic acid are reacted in a solvent to generate a quaternary phosphonium salt, and then reacted at low temperature and under the action of a strong base to generate a stable phosphonium ylide, and finally the pH value is adjusted to acidic to generate 2-(triphenylphosphine) propionic acid); Condition 2: In step (A), the reaction is carried out in a solvent, and the solvent is preferably at least one of an aromatic hydrocarbon solvent and an ether solvent; Condition 3: In step (B), the reaction is carried out in the presence of a solvent, and the solvent is preferably at least one of an alcohol solvent, a benzene solvent, and an ether solvent; Condition 4: In step (C), the reaction is carried out in the presence of a solvent; the solvent is preferably at least one of dichloromethane, dichloroethane and toluene; Condition 5: In step (D), the reaction is carried out in the presence of a solvent, and the solvent is preferably at least one of dichloromethane, dichloroethane and toluene.

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