A preparation method of alkene compounds

Abstract

The present invention discloses a method for preparing allene compounds, comprising: S1, subjecting compound I to a substitution reaction with iodobenzene diacetate to obtain compound II; S2, subjecting compound II to a Suzuki coupling reaction with compound VIII to obtain compound III; S3, subjecting compound III to an acyl chloride reaction to obtain compound IV; S4, subjecting compound IV to a Friedel-Crafts acylation reaction with AlCl3 to obtain compound V; S5, subjecting compound V to a substitution reaction with Tf2O to obtain compound VI; and S6, subjecting compound VI to a palladium-catalyzed reaction to obtain compound VII; wherein R1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, or other alkyl groups; and R2 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, or other alkyl groups. The preparation method of the present invention can be used to artificially synthesize allenes and allene compounds, facilitating industrial production. The structural formulas of compounds I, II, III, IV, V, VI, VII, and VIII are as follows:

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and in particular relates to a method for preparing an alkene compound. Background Art

[0002] Olefins are a class of hydrocarbons with unique chemical properties that play a crucial role in many organic chemical reactions. Among them, olefins are a particularly important class of olefin compounds, with a wide range of mechanisms of action and applications.

[0003] Allenes are characterized by a methyl substituent on either side of their double bond. This molecular structure allows allenes to undergo reversible cycloaddition and open-chain addition reactions. Furthermore, this structure makes allenes more susceptible to stereoisomerization and isomerization reactions than ordinary alkenes, resulting in a wide range of photochemical and photophysical effects.

[0004] In chemical reactions, allenes primarily function by participating in various mono-, di-, and tri-linear addition reactions. For example, allenes, combined with certain ligands, can be used to perform asymmetric catalytic hydrogenation reactions of aromatic and aliphatic compounds, resulting in the synthesis of highly active and selective chiral compounds. Furthermore, allenes are widely used in organic synthesis, pharmaceutical synthesis, materials chemistry, and other fields, generating numerous important research findings and practical applications.

[0005] Allenes are typically obtained through plant extraction. Currently, no effective mechanism for their synthesis has been identified, and research on related synthetic routes is limited. Extracting allenes and allene-like compounds from natural products is expensive and difficult to obtain. Therefore, developing a synthetic method for allenes and allene-like compounds is crucial. Summary of the Invention

[0006] The present invention aims to provide a method for preparing allene compounds, which can prepare allenes and allene compounds by artificial synthesis, thereby solving the problem that allenes and allene compounds can only be obtained by plant extraction.

[0007] To achieve the above object, the present invention adopts the following technical solutions:

[0008] As a first aspect of the present invention, a method for preparing an alkene compound is provided, comprising the following steps:

[0009] S1. Substitution reaction of compound I with iodobenzene diacetate to obtain compound II;

[0010] S2. Performing a Suzuki coupling reaction of compound II and compound VIII to obtain compound III;

[0011] S3, subjecting compound III to an acyl chloride reaction to obtain compound IV;

[0012] S4, subjecting compound IV to a Friedel-Crafts acylation reaction with AlCl 3 to obtain compound V;

[0013] S5. Substitution reaction of compound V with Tf2O (trifluoromethanesulfonic anhydride) to obtain compound VI;

[0014] S6. subjecting compound VI to a palladium-catalyzed reaction to obtain compound VII;

[0015] Wherein, R1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl or other alkane groups;

[0016] R2 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl or other alkane groups,

[0017] Among them, the structural formulas of Compound I, Compound II, Compound III, Compound IV, Compound V, Compound VI, Compound VII and Compound VIII are as follows:

[0018]

[0019] According to the present invention, in S1, iodobenzene diacetate is subjected to a substitution reaction with compound I in a first solvent containing a first catalyst to generate compound II;

[0020] The first catalyst is palladium acetate [Pd(OAc)2] and iodine;

[0021] The first solvent is DMF (N,N-dimethylformamide) and water; or, the first solvent is DME (ethylene glycol dimethyl ether) and water;

[0022] The molar ratio of iodobenzene diacetate to compound I is 1:1-1:2.

[0023] According to the present invention, in S2, compound II and compound VIII are subjected to a Suzuki coupling reaction in a second solvent containing a second catalyst to generate compound III;

[0024] The second catalyst is Pd(dppf)Cl2 (DPPF palladium dichloride) and K2CO3; or, the second catalyst is Pd(dppf)Cl2 and Na2CO3;

[0025] The second solvent is 1,4-dioxane and water;

[0026] The molar ratio of compound II to compound VIII is 1:1-1:2.

[0027] According to the present invention, in S3, compound III is subjected to an acyl chloride reaction in the presence of thionyl chloride (SOCl2) or oxalyl chloride (C2Cl2O2) to generate compound IV.

[0028] According to the present invention, in S4, compound IV is subjected to a Friedel-Crafts acylation reaction with AlCl3 in a third solvent to generate compound V;

[0029] The third solvent is 1,4-dioxane or tetrahydrofuran (THF);

[0030] The molar ratio of compound IV to AlCl3 is 1:1-1:2.

[0031] According to the present invention, in S5, compound V is subjected to a substitution reaction with Tf2O in a fourth solvent containing a third catalyst to generate compound VI;

[0032] The third catalyst is a base and DIEA (N,N-diisopropylethylamine); or, the third catalyst is a base and triethylamine (TEA);

[0033] The fourth solvent is dichloromethane (DCM) or tetrahydrofuran;

[0034] The molar ratio of the compound V to Tf2O is 1:1-1:2.

[0035] According to the present invention, in S6, compound VI is subjected to a palladium-catalyzed reaction in a fifth solvent containing a fourth catalyst to generate compound VII;

[0036] The fourth catalyst is palladium acetate, triphenylphosphine (PPh3), triethylamine and formic acid (HCOOH);

[0037] The fifth solvent is DMF, toluene, 1,4-dioxane or DME.

[0038] According to the present invention, the temperature for the substitution reaction of S1 is 50-80°C;

[0039] The reaction temperature of the Suzuki coupling reaction of S2 is 60-80°C;

[0040] The temperature for the acyl chloride reaction of S3 is 25-80°C;

[0041] The temperature for the Friedel-Crafts acylation reaction of S4 is 10-40°C;

[0042] The temperature for the substitution reaction of S5 is 0-25°C;

[0043] The temperature for the palladium catalytic reaction of S6 is 40-80°C.

[0044] Preferably, the temperature for the substitution reaction of S1 is 60°C;

[0045] The reaction temperature of the Suzuki coupling reaction of S2 is 60°C;

[0046] The temperature for the acyl chloride reaction of S3 is 70°C;

[0047] The temperature for the Friedel-Crafts acylation reaction of S4 is 25°C;

[0048] The temperature for the palladium-catalyzed reaction of S6 is 60°C.

[0049] Optionally, R1 is methyl, R2 is isopropyl, and the compound VII is allene.

[0050] Optionally, R1 is ethyl, R2 is ethyl, and the compound VII is 1,7-diethylphenanthrene.

[0051] Beneficial effects of the present invention:

[0052] The use of artificial synthesis to prepare allene compounds, rather than relying solely on plant extraction, facilitates the research and application of allenes in various fields. Furthermore, this method is simple to operate, uses readily available raw materials, and is readily scalable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 is a high performance liquid chromatogram of compound II prepared in Example 1;

[0054] Figure 2 is the mass spectrum of compound II prepared in Example 1;

[0055] Figure 3 is the hydrogen nuclear magnetic resonance spectrum of compound II prepared in Example 1;

[0056] Figure 4 is a high performance liquid chromatogram of compound III prepared in Example 1;

[0057] Figure 5 is the mass spectrum of compound III prepared in Example 1;

[0058] Figure 6 is the H NMR spectrum of compound III prepared in Example 1;

[0059] Figure 7 is a high performance liquid chromatogram of compound V prepared in Example 1;

[0060] Figure 8 is the mass spectrum of compound V prepared in Example 1;

[0061] Figure 9 is the hydrogen nuclear magnetic resonance spectrum of compound V prepared in Example 1;

[0062] Figure 10 is a high performance liquid chromatogram of compound VII prepared in Example 1;

[0063] Figure 11 is the H NMR spectrum of compound VII prepared in Example 1;

[0064] Figure 12 is a high performance liquid chromatogram of compound I prepared in Example 2;

[0065] Figure 13 is the mass spectrum of compound Ⅰ prepared in Example 2;

[0066] Figure 14 is the H NMR spectrum of Compound Ⅰ prepared in Example 2;

[0067] Figure 15 is the H NMR spectrum of compound II prepared in Example 2;

[0068] Figure 16 is a high performance liquid chromatogram of compound III prepared in Example 2;

[0069] Figure 17 is the mass spectrum of compound III prepared in Example 2;

[0070] Figure 18 is the H NMR spectrum of compound III prepared in Example 2;

[0071] Figure 19 is a high performance liquid chromatogram of compound V prepared in Example 2;

[0072] Figure 20 is the mass spectrum of compound V prepared in Example 2;

[0073] Figure 21 is the hydrogen nuclear magnetic resonance spectrum of compound V prepared in Example 2;

[0074] Figure 22 is the hydrogen nuclear magnetic resonance spectrum of compound VII prepared in Example 2. DETAILED DESCRIPTION

[0075] The present invention will be further explained below with reference to specific examples. The following examples are intended to illustrate the present invention only and are not intended to limit the scope of the present invention. The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial sources.

[0076] Example 1 Preparation method of propylene glycol

[0077] The synthetic route of alkene is as follows:

[0078]

[0079] 1. Prepare 2-iodo-6-methylphenylacetic acid by substitution reaction of 2-methylphenylacetic acid and iodobenzene diacetate:

[0080]

[0081] 2-Methylphenylacetic acid (8.00 g, 53.3 mmol, 1.00 eq) was dissolved in 100 mL of N,N-dimethylformamide (DMF), and iodobenzene diacetate (17.2 g, 53.3 mmol, 1.00 eq), palladium acetate (597 mg, 2.66 mmol, 0.05 eq), and iodine (14.9 g, 58.6 mmol, 1.10 eq) were added. The reaction solution was reacted at 60°C under a lightless, nitrogen atmosphere for 12 hours.

[0082] After the reaction was completed, as monitored by LCMS, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with saturated sodium thiosulfate and brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified on a flash silica gel column to obtain the product, 2-iodo-6-methylphenylacetic acid. The product weighed 7.20 g, with a yield of 48.9%.

[0083] The characterization data are as follows:

[0084] LCMS: m / z: 275.0 [MH] - (As attached Figure 1 and attached Figure 2 shown);

[0085] 1 H NMR (400 MHz, DMSO-d6) δ 12.43 (s, 1H), 7.69 (dd,, J = 7.9, 1.3 Hz, 1H), 7.20 (m, J = 7.5 Hz, 1H), 6.90 (m, J = 7.7 Hz, 1H), 3.81 (s, 2H), 2.30 (s, 3H) (as attached Figure 3 shown).

[0086] 2. Prepare 2-(4'-isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetic acid by Suzuki coupling reaction of 2-iodo-6-methylphenylacetic acid and (4-isopropylphenyl)boronic acid:

[0087]

[0088] 2-Iodo-6-methylphenylacetic acid (8.00 g, 29.0 mmol, 1.00 eq), (4-isopropylphenyl)boric acid (5.70 g, 34.8 mmol, 1.20 eq), potassium carbonate (12.0 g, 86.9 mmol, 3.00 eq), and Pd(dppf)Cl2·CH2Cl2 (0.45 g, 0.58 mmol, 0.02 eq) were dissolved in 80.0 mL of dioxane and 8.00 mL of water, and the reaction solution was reacted at 60°C under a nitrogen atmosphere for 12 hours.

[0089] The reaction was complete as monitored by LCMS. The reaction solution was diluted with water, and the pH was adjusted to acidic with 1M hydrochloric acid. The mixture was extracted with ethyl acetate. The combined organic phases were washed with brine, dried, filtered, concentrated, and purified on a flash silica gel column to yield 2-(4'-isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetic acid. The product weighed 6.60 g with a purity of 76.6%.

[0090] The characterization data are as follows:

[0091] LCMS: m / z: 267.2 [MH] - (As attached Figure 4 、 5 shown);

[0092] 1 H NMR (400MHz, DMSO-d6) δ12.36(s,1H),7.30(m,J=8.2Hz,2H),7.21-7.17(m,4H),7.04(m,J= 6.2, 2.9Hz, 1H), 3.47 (s, 2H), 2.93 (m, J=6.9Hz, 1H), 2.26 (s, 3H), 1.24 (d, J=6.9Hz, 6H). (As attached Figure 6 shown).

[0093] 3. Prepare 2-(4'-isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetyl chloride by reacting 2-(4'-isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetic acid with acetyl chloride:

[0094]

[0095] 2-(4'-Isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetic acid (7.00 g, 26.1 mmol, 1.00 eq) was dissolved in 5.00 mL of thionyl chloride (SOCl2), and the reaction solution was stirred at 70°C for 0.5 hours.

[0096] The reaction was completed by TLC monitoring. The reaction solution was concentrated under reduced pressure to obtain 2-(4'-isopropyl-3-methyl-[[1,1'-diphenyl]-2-yl)acetyl chloride. The crude product weighed 7.00 g.

[0097] 4. Prepare 7-isopropyl-1-methylphenanthren-9(10H)-one by Friedel-Crafts acylation of 2-(4'-isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetyl chloride:

[0098]

[0099] 2-(4'-Isopropyl-3-methyl-[1,1'-diphenyl]-2-yl)acetyl chloride (7.00 g, 24.4 mmol, 1.00 eq) was dissolved in 70.0 mL of toluene, and aluminum trichloride (3.25 g, 24.4 mmol, 1.00 eq) was added. The reaction solution was reacted at 25°C for 2 hours.

[0100] The reaction was complete after LCMS monitoring. The reaction solution was concentrated under reduced pressure, diluted with ethyl acetate, filtered, washed with water, and dried over anhydrous sodium sulfate. After concentration, the extract was purified on a flash silica gel column to yield 7-isopropyl-1-methylphenanthren-9(10H)-one. The product weighed 2.50 g, with a yield of 40.9%.

[0101] The characterization data are as follows:

[0102] LCMS: m / z: 249.2 [MH] - (As attached Figure 7 、 8 shown);

[0103] 1 H NMR (400MHz, DMSO-d6) δ10.30(s,1H),8.69(d,,J=8.6Hz,1H),8.51(d,J=8.0Hz,1H),8.09(d,J=2.0Hz,1H),7.60(d d,J=8.6,2.0Hz,1H),7.39-7.28(m,2H),7.20(s,1H),3.13(m,J=6.9Hz,1H),2.59(s,3H),1.33(d,J=6.9Hz,6H). (As attached Figure 9 shown.)

[0104] 5. Prepare 7-isopropyl-1-methylphenanthrene-9-yl trifluoromethanesulfonate by substitution reaction of 7-isopropyl-1-methylphenanthrene-9(10H)-one:

[0105]

[0106] 7-Isopropyl-1-methylphenanthrene-9(10H)-one (500 mg, 2.00 mmol, 1.00 eq) was dissolved in 5.00 mL of dichloromethane, and N,N-diisopropylethylamine (774 mg, 6.00 mmol, 3.00 eq) was added. Trifluoromethanesulfonic anhydride (676 mg, 2.40 mmol, 1.20 eq) was added dropwise to the reaction solution at 0°C, and the reaction solution was reacted at 25°C for 0.5 hour.

[0107] The reaction was monitored by TLC. The reaction solution was diluted with water and extracted with dichloromethane. The organic phases were combined and concentrated under reduced pressure to obtain 7-isopropyl-1-methylphenanthren-9-yl trifluoromethanesulfonate. The crude product weighed 800 mg.

[0108] 6. Prepare 7-isopropyl-1-methylphenanthrene from 7-isopropyl-1-methylphenanthrene-9-yl trifluoromethanesulfonate via palladium catalysis:

[0109]

[0110] 7-Isopropyl-1-methylphenanthren-9-yl trifluoromethanesulfonate (800 mg, 2.10 mmol, 1.00 eq) was dissolved in 5.00 mL of N,N-dimethylformamide (DMF), and palladium acetate (9.39 mg, 0.04 mmol, 0.02 eq), triphenylphosphine (22.0 mg, 0.08 mmol, 0.04 eq), triethylamine (2.19 g, 8.37 mmol, 3.00 eq), and formic acid (193 mg, 4.18 mmol, 2.00 eq) were added. The reaction solution was reacted at 60°C for 0.5 hour.

[0111] After the reaction was completed as monitored by LCMS, the reaction solution was diluted with water and extracted with ethyl acetate (EA). The combined organic phases were dried, concentrated under reduced pressure, and purified on a flash silica gel column to obtain 7-isopropyl-1-methylphenanthrene. The product weighed 300 mg, with a yield of 61.1%.

[0112] The characterization data are as follows:

[0113] HPLC: 220nm 99.56% purity (as attached Figure 10 shown);

[0114] 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.6 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.78-7.68 (m, 2H), 7.59-7.49 (m, 2H), 7.42 (m, 1H), 3.18-3.08 (m, 1H), 2.75 (s, 3H), 1.38 (d, J = 6.9 Hz, 6H). (As attached Figure 11 shown).

[0115] Product 7 is the final product of this example, 7-isopropyl-1-methylphenanthrene, with a CAS number of 483-65-8.

[0116] Example 2 Preparation method of 1,7-diethylphenanthrene

[0117] The synthetic route of 1,7-diethylphenanthrene is as follows:

[0118]

[0119] 1. Preparation of 2-(2-ethylphenyl)acetic acid:

[0120]

[0121] Since 2-(2-ethylphenyl)acetic acid is not available on the market, it needs to be prepared from (2-ethylphenyl)boronic acid through a two-step reaction before the subsequent reaction.

[0122] (2-Ethylphenyl)boronic acid (3.00 g, 20.0 mmol, 1.00 eq) was dissolved in 30.0 mL of tetrahydrofuran (THF), and ethyl bromoacetate (6.68 g, 40.0 mmol, 2.00 eq), benzyltriethylammonium bromide (545 mg, 2.00 mmol, 0.10 eq), tri-o-methylphenylphosphine (54.8 mg, 0.18 mmol, 0.009 eq), potassium fluoride (3.49 mg, 60.0 mmol, 3.00 eq), dibenzyldiallyl acetone palladium (34.5 mg, 0.06 mmol, 0.003 eq), and tetradecane (50 μL) were added. The reaction solution was reacted at 60° C. under a nitrogen atmosphere for 24 hours.

[0123] After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The crude product was dissolved in ethanol (20.0 mL) and water (10.0 mL), potassium hydroxide (2.24 g, 40.0 mmol, 2.00 eq) was added, and the reaction mixture was stirred at 25°C for 2 hours.

[0124] After the reaction was completed as monitored by LCMS, the reaction solution was acidified and extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by reverse phase column chromatography to obtain 2-(2-ethylphenyl)acetic acid.

[0125] The product weighed 3.00 g, with a yield of 91.3%.

[0126] The characterization data are as follows:

[0127] LCMS: m / z: 163.2 [MH] - (As attached Figure 12 、 13 shown).

[0128] 1 H NMR (400 MHz, CDCl3) δ 9.97 (s, 1H), 7.27-7.14 (m, 4H), 3.68 (s, 2H), 2.66 (d, J = 7.5 Hz, 2H), 1.21 (t, J = 7.6 Hz, 3H). (As attached Figure 14 shown).

[0129] 2. Preparation of 2-iodo-6-ethylphenylacetic acid from 2-ethylphenylacetic acid:

[0130]

[0131] 2-Ethylphenylacetic acid (3.00 g, 18.3 mmol, 1.00 eq) was dissolved in 40.0 mL of N,N-dimethylformamide, and iodobenzene diacetate (8.83 g, 27.4 mmol, 1.50 eq), palladium acetate (410 mg, 1.83 mmol, 0.10 eq), and iodine (6.96 g, 27.4 mmol, 1.50 eq) were added. The reaction solution was reacted at 60°C under a lightless, nitrogen atmosphere for 12 hours.

[0132] The reaction was complete after LCMS monitoring. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phases were combined, washed with saturated sodium thiosulfate and brine, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified on a flash silica gel column to obtain 2-iodo-6-ethylphenylacetic acid.

[0133] The product weighed 1.00 g, with a yield of 18.9%.

[0134] The characterization data are as follows:

[0135] 1H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 7.70 (dd, J = 7.8, 1.3 Hz, 1H), 7.22 (dd, J = 7.6, 1.2 Hz, 1H), 6.96 (t, J = 7.7 Hz, 1H), 3.82 (s, 2H), 2.63 (m, J = 7.6 Hz, 2H), 1.11 (t, J = 7.5 Hz, 3H). (As attached Figure 15 shown).

[0136] 3. Preparation of 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetic acid from 2-iodo-6-ethylphenylacetic acid:

[0137]

[0138] 2-iodo-6-ethylphenylacetic acid (1.00 g, 3.45 mmol, 1.00 eq), (4-ethylphenyl)boronic acid (776 mg, 5.17 mmol, 1.50 eq), potassium carbonate (1.43 g, 10.3 mmol, 3.00 eq), and Pd(dppf)Cl2·CH2Cl2 (27.0 mg, 0.03 mmol, 0.01 eq) were dissolved in 10.0 mL of dioxane and 1.00 mL of water, and the reaction solution was reacted at 60°C under a nitrogen atmosphere for 12 hours.

[0139] The reaction was completed by LCMS monitoring. The reaction solution was diluted with water, and the pH of the reaction solution was adjusted to acidic with 1 mol / L hydrochloric acid. The solution was extracted with ethyl acetate, and the organic phases were combined, washed with brine, dried, filtered, concentrated, and purified on a flash silica gel column to obtain 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetic acid.

[0140] The product weighed 0.90 g and the yield was 97.2%. When the reaction was carried out at a temperature above 80°C, the product was more mixed.

[0141] The characterization data are as follows:

[0142] LCMS: m / z: 267.2 [MH] - (As attached Figure 16 、 17 shown);

[0143] 1H NMR (400 MHz, DMSO-d6) δ 12.33 (s, 1H), 7.29-7.20 (m, 4H), 7.19-7.14 (m, 2H), 7.02 (dd, J = 7.1, 1.9 Hz, 1H), 3.48 (s, 2H), 2.62 (m, J = 24.5, 7.5 Hz, 4H), 1.20 (m, J = 16.9, 7.5 Hz, 6H). (As attached Figure 18 shown).

[0144] 4. Preparation of 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetyl chloride from 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetic acid:

[0145]

[0146] 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetic acid (100 mg, 0.37 mmol, 1.00 eq) was dissolved in 1.00 mL of thionyl chloride, and the reaction solution was stirred at 70°C for 0.5 hours.

[0147] The reaction was completed by TLC monitoring. The reaction solution was concentrated under reduced pressure to obtain 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetyl chloride. The crude product weighed 150 mg.

[0148] 5. Preparation of 1,7-diethylphenanthren-9(10H)-one from 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetyl chloride:

[0149]

[0150] 2-(3,4'-diethyl-[1,1'-biphenyl]-2-yl)acetyl chloride (150 mg, 24.4 mmol, 1.00 eq) was dissolved in 3.00 mL of toluene, and aluminum trichloride (93.0 mg, 0.70 mmol, 2.00 eq) was added. The reaction solution was reacted at 25°C for 2 hours.

[0151] The reaction was completed by LCMS monitoring. The reaction solution was concentrated under reduced pressure, diluted with ethyl acetate, filtered, washed with water, and extracted. The product was then dried over anhydrous sodium sulfate and concentrated, and purified on a flash silica gel column to obtain compound 5, which was tautomerized to 1,7-diethylphenanthren-9(10H)-one.

[0152] The product weighed 40.0 mg, with a yield of 30.5%.

[0153] The characterization data are as follows:

[0154] LCMS: m / z: 249.2 [MH]- (As attached Figure 19 、 20 shown);

[0155] 1 H NMR (400MHz, CDCl3) δ8.60(d,J=8.5Hz,1H),8.47(d,J=8.0Hz,1H),8.09(m,J=1.9Hz,1H),7.54(dd,J=8.5,1.9Hz,1H),7 .45-7.36(m,2H),7.24(s,1H),5.31(s,1H),3.05(q,J=7.5Hz,2H),2.90(q,J=7.6Hz,2H),1.38(m,J=7.6,3.3Hz,6H).(As attached Figure 21 shown).

[0156] 6. Preparation of 1,7-diethylphenanthren-9-yl trifluoromethanesulfonate from 1,7-diethylphenanthren-9(10H)-one:

[0157]

[0158] 1,7-Diethylphenanthren-9(10H)-one (30.0 mg, 0.12 mmol, 1.00 eq) was dissolved in 1.00 mL of dichloromethane, and N,N-diisopropylethylamine (31.0 mg, 0.24 mmol, 2.00 eq) was added. Trifluoromethanesulfonic anhydride (67.6 mg, 0.24 mmol, 2.00 eq) was added dropwise to the reaction solution at 0°C, and the reaction solution was reacted at 25°C for 0.5 hour.

[0159] The reaction was completed by TLC monitoring. The reaction solution was diluted with water, extracted with dichloromethane, and the combined organic phases were concentrated under reduced pressure to obtain 1,7-diethylphenanthren-9-yl trifluoromethanesulfonate.

[0160] The crude product weighed 40.0 mg.

[0161] 7. Preparation of 1,7-diethylphenanthrene from 1,7-diethylphenanthrene-9-yl trifluoromethanesulfonate:

[0162]

[0163] 1,7-Diethylphenanthren-9-yl trifluoromethanesulfonate (45.0 mg, 0.12 mmol, 1.00 eq) was dissolved in 2.00 mL of N,N-dimethylformamide, and palladium acetate (0.50 mg, 0.002 mmol, 0.02 eq), triphenylphosphine (1.26 mg, 0.005 mmol, 0.04 eq), triethylamine (36.4 mg, 0.36 mmol, 3.00 eq), and formic acid (11.0 mg, 0.24 mmol, 2.00 eq) were added. The reaction solution was reacted at 60°C for 2 hours.

[0164] The reaction was completed by LCMS monitoring. The reaction solution was diluted with water and extracted with ethyl acetate. The organic phases were combined, dried, concentrated under reduced pressure, and purified on a flash silica gel column to obtain 1,7-diethylphenanthrene.

[0165] The product weighed 10.0 mg, with a yield of 40.7%.

[0166] The characterization data are as follows:

[0167] 1 H NMR (400MHz, CDCl3) δ8.61(d,J=8.5Hz,1H),8.55(d,J=8.3Hz,1H),7.98(d,J=9.2,0.8Hz,1H),7.73(d,J=9.2Hz,1H),7.70-7.67(m,1H),7.56(m,J=8 .4,7.1Hz,1H),7.50(dd,J=8.5,1.9Hz,1H),7.43(d,J=7.5,0.9Hz,1H),3. 16(q,J=7.6Hz,2H),2.86(q,J=7.6Hz,2H),1.38(m,J=15.2,7.6Hz,6H).(As attached Figure 22 shown).

[0168] The above description is merely an example of the implementation of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing an alkene compound, characterized in that: The steps include: S1. Substitution reaction of compound I with iodobenzene diacetate to obtain compound II; S2. Performing a Suzuki coupling reaction of compound II and compound VIII to obtain compound III; S3, subjecting compound III to an acyl chloride reaction to obtain compound IV; S4, subjecting compound IV to a Friedel-Crafts acylation reaction with AlCl 3 to obtain compound V; S5, subjecting compound V to a substitution reaction with Tf2O to obtain compound VI; S6. subjecting compound VI to a palladium-catalyzed reaction to obtain compound VII; Wherein, R1 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl or other alkane groups; R2 is methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl or other alkane groups, Among them, the structural formulas of Compound I, Compound II, Compound III, Compound IV, Compound V, Compound VI, Compound VII and Compound VIII are as follows:

2. The preparation method according to claim 1, wherein In S1, iodobenzene diacetate is subjected to a substitution reaction with compound I in a first solvent containing a first catalyst to generate compound II; The first catalyst is palladium acetate and iodine; The first solvent is DMF and water; or, the first solvent is DME and water; The molar ratio of iodobenzene diacetate to compound I is 1:1-1:

2.

3. The preparation method according to claim 1, wherein In S2, compound II and compound VIII are subjected to a Suzuki coupling reaction in a second solvent containing a second catalyst to produce compound III; The second catalyst is Pd(dppf)Cl2 and K2CO3; or, the second catalyst is Pd(dppf)Cl2 and Na2CO3; The second solvent is 1,4-dioxane and water; The molar ratio of compound II to compound VIII is 1:1-1:

2.

4. The preparation method according to claim 1, wherein In the above S3, compound III is subjected to an acyl chloride reaction in the presence of thionyl chloride or oxalyl chloride to generate compound IV.

5. The preparation method according to claim 1, wherein In S4, compound IV is subjected to a Friedel-Crafts acylation reaction with AlCl3 in a third solvent to generate compound V; The third solvent is 1,4-dioxane or tetrahydrofuran; The molar ratio of compound IV to AlCl3 is 1:1-1:

2.

6. The preparation method according to claim 1, wherein In S5, compound V is subjected to a substitution reaction with Tf2O in a fourth solvent containing a third catalyst to generate compound VI; The third catalyst is a base and DIEA; or, the third catalyst is a base and triethylamine; The fourth solvent is dichloromethane or tetrahydrofuran; The molar ratio of the compound V to Tf2O is 1:1-1:

2.

7. The preparation method according to claim 1, wherein In S6, compound VI is subjected to a palladium-catalyzed reaction in a fifth solvent containing a fourth catalyst to generate compound VII; The fourth catalyst is palladium acetate, triphenylphosphine, triethylamine and formic acid; The fifth solvent is DMF, toluene, 1,4-dioxane or DME.

8. The preparation method according to any one of claims 1 to 7, wherein The temperature for the substitution reaction of S1 is 50-80°C; The reaction temperature of the Suzuki coupling reaction of S2 is 60-80°C; The temperature for the acyl chloride reaction of S3 is 25-80°C; The temperature for the Friedel-Crafts acylation reaction of S4 is 10-40°C; The temperature for the substitution reaction of S5 is 0-25°C; The temperature for the palladium catalytic reaction of S6 is 40-80°C.

9. The preparation method according to any one of claims 1 to 7, wherein The R1 is methyl, R2 is isopropyl, and the compound VII is allene.

10. The preparation method according to any one of claims 1 to 7, characterized in that: The R1 is an ethyl group, R2 is an ethyl group, and the compound VII is 1,7-diethylphenanthrene.

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