An alpha-alkylenelactone compound and a method for preparing an alpha-alkylenelactone compound from a cyclopropenone derivative

Abstract

The application belongs to the technical field of compound preparation, and particularly relates to an alpha-alkylidene lactone compound and a method for preparing the alpha-alkylidene lactone compound from a cyclopropenone derivative. The method comprises the following steps: first, synthesizing a substrate cyclopropenone derivative; then, stirring the cyclopropenone derivative, AgBF4 and ethylene glycol dimethyl ether in a Shrek bottle at 80 DEG C; and finally, concentrating and purifying the mixture by column chromatography to obtain the alpha-alkylidene lactone compound. The previous synthesis method can only be applied to the synthesis of one or several types of alpha-alkylidene lactone compounds, while the method can realize the synthesis of alpha-alkylidene-beta-lactone, alpha-alkylidene-gamma-lactone, alpha-alkylidene-delta-lactone and alpha-alkylidene-epsilon-lactone compounds, and has good universality. The method has stereo-specificity in the synthesis of alpha-alkylidene lactone compounds. The method uses a cheap catalyst, has high reaction yield, and is convenient to prepare the substrate, and has good applicability.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of compound preparation, and particularly relates to an alpha-alkylidene lactone compound and a method for preparing the alpha-alkylidene lactone compound from a cyclopropenone derivative. BACKGROUND

[0002] Alpha-alkylidene lactone compounds are widely present in important compounds such as natural products, drug molecules and functional molecules, and have wide application prospects in the following fields:

[0003] (1) In the field of perfumes and essences: alpha-alkylidene lactone compounds have unique aroma and taste, and are therefore widely used as ingredients of perfumes and essences. They can be used in food, cosmetics, detergents and perfumes and other products to add pleasant sensory experience.

[0004] (2) In the field of drug synthesis: alpha-alkylidene lactone compounds can be used as key intermediates for drug synthesis, for synthesizing compounds with biological activity. For example, certain alpha-alkylidene lactone compounds have antibacterial, anti-inflammatory, antitumor and other activities, and can be used for developing new drugs.

[0005] (3) In the field of pesticides: alpha-alkylidene lactone compounds can also be used as effective ingredients of pesticides for preventing and controlling crop diseases and pests. They can interfere with the growth and development of pests or destroy their reproductive ability, thereby protecting crops from damage.

[0006] (4) In the field of material science: alpha-alkylidene lactone compounds can be used as monomers or additives of high polymer materials for preparing polymers, coatings, adhesives and the like. They can improve the performance of materials, such as enhancing toughness and improving heat resistance.

[0007] (5) In the field of environmental protection: alpha-alkylidene lactone compounds can be used as part of biodegradable materials for preparing degradable plastics, fibers and the like. These materials can be decomposed by microorganisms in the natural environment after use, reducing pollution to the environment.

[0008] Therefore, it is of great significance to carry out research on the synthesis method of alpha-alkylidene lactone compounds.

[0009] The main synthesis methods of the α-alkylidene lactone compounds at present include aldol condensation, intramolecular lactonization of α, β-unsaturated carboxylic acid, olefin metathesis reaction and palladium catalyzed carbon monoxide insertion reaction and the like. These routes have problems such as poor compatibility of substrate functional groups, difficulty in preparation of substrates or excessive preparation cost caused by use of noble metal catalysts. Therefore, it is urgent to develop a new route which not only overcomes the above-mentioned defects, but also can realize efficient synthesis of α-alkylidene-β-lactone (tetra-lactone), α-alkylidene-γ-lactone (penta-lactone), α-alkylidene-δ-lactone (hexa-lactone) and α-alkylidene-ε-lactone (hepta-lactone) and the like compounds through substrate adjustment. SUMMARY

[0010] The present application aims to provide an α-alkylidene lactone compound and a method for preparing the α-alkylidene lactone compound from a cyclopropenone derivative. The method of the present application can efficiently, stereoselectively and directionally obtain the high-value-added α-alkylidene lactone compound under the action of a cheap and common catalyst, with a cyclopropenone derivative containing a hydroxyl group as a raw material.

[0011] The implementation process of the present application is as follows:

[0012] A method for preparing an α-alkylidene lactone compound from a cyclopropenone derivative, comprising the following steps:

[0013] (1) Preparation of compound a

[0014] CuI, Pd(PPh3)2Cl2, triethylamine and R-I are added into a container and stirred, and then After stirring and reaction, the mixture is filtered, concentrated, and separated and purified by column chromatography to obtain compound a;

[0015] (2) Preparation of compound b

[0016] Compound a, anhydrous dichloromethane, p-toluenesulfonic acid and 3,4-dihydro-2H-pyran are added into a container and stirred under nitrogen atmosphere at 0℃ ice water bath, and then saturated sodium bicarbonate solution is added into the container to adjust pH=7. The mixture is extracted, washed, dried, solvent-removed and separated and purified by column chromatography to obtain compound b;

[0017] (3) Preparation of compound c

[0018] In a container, compound b, anhydrous tetrahydrofuran, NaI were added and stirred under nitrogen atmosphere at 0℃, then TMSCF3 was added, and the reaction was continued to stir at 25℃, after the reaction was completed, water was added to the container, the mixture was extracted, washed, dried, and the concentrated product after solvent removal was transferred to the container, and dichloromethane and SiO2 were added to the container, the reaction was stirred at room temperature, and the reaction solution was filtered, evaporated, and purified by column chromatography to obtain compound c;

[0019] (4) Preparation of compound d

[0020] Compound c was dissolved in methanol, macroporous resin Amberlyst 15 was added and stirred to react, and the mixture was filtered, the solvent was removed, and compound d was obtained by column chromatography.

[0021] (5) Preparation of compound f α-alkylene lactone compound

[0022] Compound d, AgBF4, and ethylene glycol dimethyl ether were added to a Schlenk flask and stirred at 80℃, and the mixture was concentrated, purified by column chromatography to obtain the target product compound f α-alkylene lactone compound.

[0023]

[0024] n = 0, 1, 2, or 3.

[0025] Further, in step (1), the molar ratio of R-I to was 11:10;

[0026] The molar ratio of compound a, CuI, and Pd(PPh3)2Cl2 was 1:0.1:0.05; The molar volume ratio of compound a to triethylamine was 1 mmol:3 mL; the eluent for column chromatography was petroleum ether:ethyl acetate at a volume ratio of 4:1.

[0027] Further, in step (2), the molar ratio of compound a, p-toluenesulfonic acid, and 3,4-dihydro-2H-pyran was 9.46:0.946:10.7; the molar volume ratio of compound a to anhydrous dichloromethane was 9.46 mmol:30 mL; the eluent for column chromatography was petroleum ether:ethyl acetate at a volume ratio of 20:1.

[0028] Further, in step (3), the molar ratio of compound b, NaI, TMSCF3, and SiO2 was 7.59:16.7:15.2:15.2; the molar volume ratio of compound b, anhydrous tetrahydrofuran, and dichloromethane was 7.59 mmol:30 mL:15 mL; the eluent for column chromatography was petroleum ether:ethyl acetate at a volume ratio of 1:1.

[0029] Further, in step (4), the molar ratio of compound c: Amberlyst 15 is 1:1; the molar volume ratio of compound c: methanol is 5.12 mmol: 30 mL; and the eluent for column chromatography separation and purification is ethyl acetate.

[0030] Further, in step (5), the molar ratio of compound d: AgBF4 is 1:0.05; the molar volume ratio of compound d: ethylene glycol dimethyl ether is 1 mmol: 5 mL; and the eluent for column chromatography separation and purification is petroleum ether: ethyl acetate with a volume ratio of 4:1.

[0031] An α-alkylidene lactone compound, the structural formula of which is as follows:

[0032] n = any one of 0, 1, 2 or 3, wherein R is selected from a phenyl group or a substituted phenyl group.

[0033] Further, the substituent of the substituted phenyl group is selected from any one of an alkoxy group with 1-6 carbon atoms, a halogen group, an alkyl group with 1-6 carbon atoms or a cyano group.

[0034] Positive effects of the present application:

[0035] (1) The previous synthesis method can only be applied to the synthesis of one or several types of α-alkylidene lactone compounds, while the method of the present application can realize the synthesis of α-alkylidene-β-lactone, α-alkylidene-γ-lactone, α-alkylidene-δ-lactone and α-alkylidene-ε-lactone compounds, and has good universality.

[0036] (2) The method of the present application exhibits stereospecificity in the synthesis of α-alkylidene lactone compounds.

[0037] (3) The method of the present application uses a cheap catalyst, has a high reaction yield, and the substrate is easy to prepare, and has good applicability. BRIEF DESCRIPTION OF DRAWINGS

[0038] Figure 1 is the 1H NMR spectrum of compound 1f α-phenylmethylene-β-lactone 1 H NMR spectrum;

[0039] Figure 2 is the 13C NMR spectrum of compound 1f α-phenylmethylene-β-lactone

[0040] Figure 3 is the 1H NMR spectrum of compound 2f α-(4-methoxyphenyl)methylene-β-lactone 1 H NMR spectrum;

[0041] Figure 4Compound 2f α-(4-methoxyphenyl)methylidene-β-lactone 13 H NMR spectrum;

[0042] Figure 5 Compound 3f α-(4-chlorophenyl)methylidene-β-lactone 1 H NMR spectrum;

[0043] Figure 6 Compound 3f α-(4-chlorophenyl)methylidene-β-lactone 13 H NMR spectrum;

[0044] Figure 7 Compound 4f α-(4-bromophenyl)methylidene-β-lactone 1 H NMR spectrum;

[0045] Figure 8 Compound 4f α-(4-bromophenyl)methylidene-β-lactone 13 H NMR spectrum;

[0046] Figure 9 Compound 5f α-phenylmethylidene-γ-lactone 1 H NMR spectrum;

[0047] Figure 10 Compound 5f α-phenylmethylidene-γ-lactone 13 H NMR spectrum;

[0048] Figure 11 Compound 6f α-(4-bromophenyl)methylidene-γ-lactone 1 H NMR spectrum;

[0049] Figure 12 Compound 6f α-(4-bromophenyl)methylidene-γ-lactone 13 H NMR spectrum;

[0050] Figure 13 Compound 7f α-(4-methoxyphenyl)methylidene-γ-lactone 1 H NMR spectrum;

[0051] Figure 14 Compound 7f α-(4-methoxyphenyl)methylidene-γ-lactone 13 H NMR spectrum;

[0052] Figure 15 Compound 8f α-phenylmethylidene-δ-lactone 1 H NMR spectrum;

[0053] Figure 16Compound 8f α-(4-bromophenyl)methylenedelta-lactone 13 H NMR spectrum;

[0054] Figure 17 Compound 9f α-(3,4-dimethylphenyl)methylenedelta-lactone 1 H NMR spectrum;

[0055] Figure 18 Compound 9f α-(3,4-dimethylphenyl)methylenedelta-lactone 13 H NMR spectrum;

[0056] Figure 19 Compound 10f α-(4-bromophenyl)methylenedelta-lactone 1 H NMR spectrum;

[0057] Figure 20 Compound 10f α-(4-bromophenyl)methylenedelta-lactone 13 H NMR spectrum;

[0058] Figure 21 Compound 11f α-(4-cyanophenyl)methylenedelta-lactone 1 H NMR spectrum;

[0059] Figure 22 Compound 11f α-(4-cyanophenyl)methylenedelta-lactone 13 H NMR spectrum;

[0060] Figure 23 Compound 12f α-(4-cyanophenyl)methylenedelta-lactone 1 H NMR spectrum;

[0061] Figure 24 Compound 12f α-(4-cyanophenyl)methylenedelta-lactone 13 H NMR spectrum. DETAILED DESCRIPTION

[0062] The application is further described in connection with the following examples.

[0063] Example 1 Preparation of α-phenylmethylene-β-lactone

[0064]

[0065] (1) Preparation of compound 1a

[0066] A round bottom flask was charged with CuI (0.19 g), Pd(PPh3)2Cl2(0.35 g), and triethylamine (30 mL) sequentially. lodobenzene (1.23 mL, 11 mmol) was added slowly to the round bottom flask and stirring was continued for 15 minutes. 2-Propyn-l-ol (0.56 g, 10 mmol) was then added slowly to the round bottom flask and stirring was continued for 6 hours. The reaction mixture was filtered and concentrated, and the product was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4: 1, V / V) to give compound la (1.25 g, 95%).

[0067] (2) Preparation of compound lb

[0068] A round bottom flask was charged with compound la (1.25 g, 9.46 mmol), anhydrous dichloromethane (30 mL), and p-toluenesulfonic acid (TsOH-H2O, 0.17 g) sequentially under nitrogen atmosphere in an ice water bath at 0 °C. 3,4-Dihydro-2H-pyran (DHP, 0.90 g, 10.7 mmol) was then added slowly to the reaction flask and stirring was continued for 24 hours. Saturated sodium bicarbonate solution (5 mL) was added slowly to the round bottom flask until pH = 7. The reaction mixture was extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated on a rotary evaporator. The product was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 20: 1, V / V) to give compound lb (1.64 g, 80%).

[0069] (3) Preparation of compound lc

[0070] A round bottom flask was charged with compound lb (1.64 g, 7.59 mmol), anhydrous tetrahydrofuran (30 mL), and NaI (2.50 g, 16.7 mmol) sequentially under nitrogen atmosphere in an ice water bath at 0 °C. The reaction mixture was stirred for 10 minutes, and then TMSCF3(2.16 g, 15.2 mmol) was added slowly, followed by stirring at 25 °C for 24 hours. After the reaction was completed, 30 mL of water was added to the flask, and the mixture was extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated on a rotary evaporator. The concentrated product was transferred to a round bottom flask, and dichloromethane (15 mL) and SiO2(0.92 g, 15.2 mmol) were added sequentially, and stirring was continued at room temperature for 24 hours. The reaction mixture was filtered, and the solvent was evaporated. The product was purified by column chromatography (eluent: petroleum ether: ethyl acetate = 1: 1, V / V) to give compound lc (1.25 g, 76%).

[0071] (4) Preparation of compound Id

[0072] Compound 1c (1.25 g, 5.12 mmol) was dissolved in 30 mL of methanol, to which macroporous resin (Amberlyst 15, 1.39 g, 5.12 mmol) was added. The reaction mixture was stirred for 3 hours, filtered, and the solvent was evaporated on a rotary evaporator, and column chromatography was used for purification (eluent: ethyl acetate) to obtain compound 1d (0.87 g, 70%).

[0073] (5) Preparation of compound 1f α-phenylmethylene-β-lactone

[0074] Compound 1d (1 mmol, 160 mg), AgBF4(5 mol%, 9 mg), ethylene glycol dimethyl ether (5 mL) were sequentially added to a Schlenk flask. The reaction mixture was stirred at 80°C for 20 hours. The reaction mixture was concentrated, and column chromatography was used for purification (eluent: petroleum ether: ethyl acetate = 4:1, V / V) to obtain compound 1f (α-phenylmethylene-β-lactone, 141 mg, 88%).

[0075] Compound 1f (α-phenylmethylene-β-lactone), white solid, melting point 86-88°C, mass 141 mg. See Figure 1 and Figure 2 .

[0076] 1 H NMR (400 MHz, Chloroform-d) δ: 7.44-7.43 (m, 3H), 7.32-7.29 (m, 2H), 7.16 (s, 1H), 5.04 (s, 2H).

[0077] 13 C NMR (101 MHz, Chloroform-d) δ: 164.9, 133.1, 132.9, 131.0, 130.8, 129.5, 67.4. HRMS (ESI) m / z: [M+H] + Calcd for C 10 H9O2 161.0597; Found 161.0600.

[0078] Example 2

[0079] Example 2 differs from Example 1 in that iodobenzene in step (1) is replaced by The rest of the steps are the same in terms of reagent amount, reaction temperature and time, etc.

[0080] The target product 2f (α-(4-methoxyphenyl)methylene-β-lactone) is a white solid, melting point 94-96°C, mass 148 mg, yield 78%. See Figure 3 andFigure 4 .

[0081] 1 H NMR (400 MHz, Chloroform-d) δ: 7.24 (d, J = 12.0 Hz, 2H), 7.10 (t, J = 4.0 Hz, 1H), 6.94 (d, J = 12.0 Hz, 2H), 4.99 (s, 2H), 3.85 (s, 3H).

[0082] 13 C NMR (101 MHz, Chloroform-d) δ: 165.3, 161.9, 131.3, 130.4, 130.2, 125.6, 114.9, 67.2, 55.6.

[0083] HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 11 O3 191.0703; Found 191.0703.

[0084] Example 3

[0085] Example 3 differs from Example 1 in that iodobenzene in step (1) is replaced by The remaining steps and reagent amounts, reaction temperature and time, and other parameters are the same.

[0086] The target product 3f (a-(4-chlorophenyl)methylene-β-lactone) is white solid, melting point 100-102 °C, mass 140 mg, yield 78%. See Figure 5 and Figure 6 .

[0087] 1 H NMR (400 MHz, Chloroform-d) δ: 7.41 (d, J = 8.0 Hz 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 4.0 Hz, 1H), 5.01 (d, J = 4.0 Hz 2H).

[0088] 13 C NMR (101 MHz, Chloroform-d) δ: 164.5, 137.2, 133.7, 131.3, 130.6, 129.8, 129.4, 67.2.

[0089] HRMS (ESI) m / z: [M+H] + Calcd for C 10H8ClO2 195.0207; Found 195.0209.

[0090] Example 4

[0091] Example 4 differs from Example 1 in that iodobenzene in step (1) is replaced by The rest of the steps are the same as the amount of reagent, reaction temperature and time, etc.

[0092] The target product 4f (a-(4-bromophenyl)methylene-β-lactone) is yellow solid, melting point 110-112 °C, mass 172 mg, yield 72%. See Figure 7 and Figure 8 .

[0093] 1 H NMR (400 MHz, DMSO-d6) δ: 7.67 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 7.33 (t, J = 4.0 Hz, 1H), 5.18 (d, J = 4.0 Hz, 2H).

[0094] 13 C NMR (101 MHz, DMSO-d6) δ: 165.0, 134.2, 132.6, 132.4, 131.8, 129.4, 124.7, 68.0.

[0095] HRMS (ESI) m / z: [M+H] + Calcd for C 10 H8BrO2 238.9702; Found 238.9705.

[0096] Example 5 Preparation of a-phenylmethylene-γ-lactone

[0097]

[0098] (1) Preparation of compound 5a

[0099] CuI (0.19 g), Pd(PPh3)2Cl2(0.35 g), triethylamine (30 mL) were added into a round bottom flask in turn. Iodobenzene (1.23 mL, 11 mmol) was slowly added into the round bottom flask and continued to stir for 15 minutes. Then 3-butyn-1-ol (0.71 g, 10 mmol) was slowly added into the round bottom flask and continued to stir for 6 hours. After TLC monitoring the disappearance of raw materials, the reaction mixture was filtered, concentrated and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1, V / V) to obtain compound 5a (1.34 g, 92%).

[0100] (2) Preparation of compound 5b

[0101] To a round bottom flask, was added compound 5a (1.34 g, 9.17 mmol), anhydrous dichloromethane (30 mL), p-toluenesulfonic acid (TsOH-H20, 0.17 g) sequentially under nitrogen atmosphere in an ice water bath at 0 °C. To the reaction flask, was added 3,4-dihydro-2H-pyran (DHP, 0.87 g, 11.3 mmol) dropwise slowly and stirred for 24 h. To the round bottom flask, was added saturated sodium bicarbonate solution (5 mL) slowly until pH = 7. The reaction mixture was extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, evaporated on a rotary evaporator, and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 20: 1, V / V) to give compound 5b (1.75 g, 83%).

[0102] (3) Preparation of compound 5c

[0103] To a round bottom flask, was added compound 5b (1.75 g, 7.61 mmol), anhydrous NaI (2.51 g, 16.74 mmol), and anhydrous tetrahydrofuran (30 mL) sequentially under nitrogen atmosphere in an ice water bath at 0 °C. To the reaction mixture, was added TMSCF3 (2.16 g, 15.22 mmol) dropwise slowly and stirred for 10 min, and then the reaction was continued at 25 °C for 24 h. After the reaction was completed, 30 mL of water was added to the system, extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and evaporated on a rotary evaporator. The concentrated product was transferred to a round bottom flask, and dichloromethane (15 mL) and Si02 (0.93 g, 15.22 mmol) were sequentially added thereto, and stirred at room temperature for 24 h. The reaction liquid was filtered, evaporated on a rotary evaporator, and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 1: 1, V / V) to give compound 5c (1.52 g, 77%).

[0104] (4) Preparation of compound 5d

[0105] Compound 5c (1.52 g, 5.89 mmol) was dissolved in 30 mL of methanol, and macroporous resin (Amberlyst 15, 1.39 g, 10 mmol) was added thereto. The reaction mixture was stirred for 3 h, filtered, evaporated on a rotary evaporator, and purified by column chromatography (eluent: ethyl acetate) to give compound 5d (0.86 g, 84%).

[0106] (5) Preparation of compound 5f α-phenyl methylene-γ-lactone

[0107] In a Schlenk flask, compound 5d (1 mmol, 174 mg), AgBF4(5 mol%, 9 mg), ethylene glycol dimethyl ether (5 mL) were added. The reaction mixture was stirred at 80 °C for 20 h. The reaction mixture was concentrated and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4:1, V / V) to give compound 5f (a-phenyl methylene-gamma-lactone 154 mg, 88%).

[0108] 5f (a-phenyl methylene-gamma-lactone), yellow oily liquid, 154 mg. See Figure 9 and Figure 10 .

[0109] 1 H NMR (400 MHz, Chloroform-d) δ: 7.58 (t, J = 4.0 Hz, 1H), 7.52-7.50 (m, 2H), 7.47-7.39 (m, 3H), 4.47 (t, J = 8.0 Hz, 2H), 3.26 (t, J = 8.0 Hz, 2H).

[0110] 13 C NMR (101 MHz, Chloroform-d) δ: 172.7, 136.8, 134.8, 130.1, 130.0, 129.1, 123.6, 65.6, 27.6.

[0111] HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 11 O2 175.0754; Found 175.0759.

[0112] Example 6

[0113] Example 6 differs from Example 5 in that iodobenzene in step (1) is replaced by The rest of the steps and reagent amounts, reaction temperature and time, etc. are the same.

[0114] The target product 6f (a-(4-bromophenyl)methylene-gamma-lactone) is yellow oily liquid, mass 212 mg, yield 84%. See Figure 11 and Figure 12 .

[0115] 1H NMR (400 MHz, Chloroform-d) δ: 7.57 (d, J = 8.0 Hz, 2H), 7.50 (t, J = 4.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 4.48 (t, J = 8.0 Hz, 2H), 3.22 (t, J = 8.0 Hz, 2H).

[0116] 13 C NMR (101 MHz, Chloroform-d) δ: 172.4, 135.5, 133.6, 132.4, 131.4, 124.4 (2C), 65.5, 27.5.

[0117] HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 10 BrO2 252.9859; Found 252.9864.

[0118] Example 7

[0119] Example 7 differs from Example 5 in that iodobenzene in step (1) is replaced by The remaining steps and reagent amounts, reaction temperature and time, and other parameters are the same.

[0120] The target product 7f (a-(4-methoxyphenyl)methylene-γ-lactone) is Yellow oily liquid, mass 175 mg, yield 86%. See Figure 13 and Figure 14 .

[0121] 1 H NMR (400 MHz, Chloroform-d) δ: 7.53 (t, J = 4.0 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 4.47 (t, J = 8.0 Hz, 2H), 3.86 (s, 3H), 3.25-3.20 (m, 2H).

[0122] 13 C NMR (101 MHz, Chloroform-d) δ: 173.1, 161.0, 136.5, 131.9, 127.6, 120.7, 114.6, 65.5, 55.5, 27.5.

[0123] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 13O3 205.0859; Found 205.0864.

[0124] Example 8 Preparation of α-phenyl methylene-δ-lactone

[0125]

[0126] (1) Preparation of compound 8a

[0127] Into a round bottom flask was added sequentially CuI (0.19 g), Pd(PPh3)2Cl2(0.35 g), triethylamine (30 mL). To the round bottom flask was added slowly iodobenzene (1.23 mL, 11 mmol) and stirring was continued for 15 minutes. To the round bottom flask was added slowly 4-pentyn-1-ol (0.84 g, 10 mmol) and stirring was continued for 6 hours. After TLC monitoring of the disappearance of starting material, the reaction mixture was filtered and concentrated, and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4: 1, V / V) to give compound 8a (1.48 g, 92%).

[0128] (2) Preparation of compound 8b

[0129] Into a round bottom flask was added sequentially compound 8a (1.48 g, 9.20 mmol), anhydrous dichloromethane (30 mL), p-toluenesulfonic acid (TsOH-H2O, 0.16 g) under nitrogen atmosphere at 0 °C. To the reaction flask was added slowly dropwise 3,4-dihydro-2H-pyran (DHP, 0.87 g, 10.40 mmol) and stirring was continued for 24 hours. To the round bottom flask was added slowly saturated sodium bicarbonate solution (5 mL) to pH = 7. The reaction mixture was extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, evaporated to dryness, and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 20: 1, V / V) to give compound 8b (2.11 g, 94%).

[0130] (3) Preparation of compound 8c

[0131] To a round bottom flask, compound 8b (2.11 g, 8.65 mmol), anhydrous NaI (2.85 g, 19.03 mmol) and anhydrous tetrahydrofuran (30 mL) were added successively under nitrogen atmosphere at 0 °C. The reaction mixture was stirred for 10 minutes, then TMSCF3 (2.46 g, 17.30 mmol) was added slowly, and the reaction was continued at 25 °C for 24 h. After the reaction was completed, 30 mL of water was added to the system, extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The concentrated product was transferred to a round bottom flask, dichloromethane (15 mL) and SiO2 (1.05 g, 17.30 mmol) were added successively, and stirred at room temperature for 24 h. The reaction liquid was filtered, the solvent was evaporated, and column chromatography was used for separation and purification (eluent: petroleum ether: ethyl acetate = 1:1, V / V) to obtain compound 8c (1.88 g, 80%).

[0132] (4) Preparation of compound 8d

[0133] Compound 8c (1.88 g, 6.92 mmol) was dissolved in 30 mL of methanol, and macroporous resin (Amberlyst 15, 1.39 g, 10 mmol) was added. The reaction mixture was stirred for 3 h, filtered, the solvent was evaporated, and column chromatography was used for separation and purification (eluent: ethyl acetate) to obtain compound 8d (1.17 g, 90%).

[0134] (5) Preparation of compound 8f α-phenylmethylene-δ-lactone

[0135] In a Schlenk flask, compound 8d (1 mmol, 188 mg), AgBF4 (5 mmol%, 9 mg), and ethylene glycol dimethyl ether 5 mL were added. The reaction mixture was reacted at 80 °C for 20 h, the reaction mixture was concentrated, and column chromatography was used for separation and purification (eluent: petroleum ether: ethyl acetate = 4:1, V / V) to obtain 8f (α-phenylmethylene-δ-lactone, 92%, 173 mg).

[0136] 8f (α-phenylmethylene-δ-lactone), colorless liquid, mass 17.3 mg. See Figure 15 and Figure 16 .

[0137] 1 H NMR (400 MHz, Chloroform-d) δ: 7.92 (t, J = 4.0 Hz, 1H), 7.45-7.35 (m, 5H), 4.40 (t, J = 8.0 Hz, 2H), 2.91-2.87 (m, 2H), 2.01-1.95 (m, 2H).

[0138] 13C NMR (101 MHz, Chloroform-d) δ: 167.1, 141.8, 135.1, 130.4, 129.3, 128.7, 125.9, 68.8, 26.1, 23.1.

[0139] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 13 O2 189.0910; Found 189.0915.

[0140] Example 9

[0141] Example 9 differs from Example 8 in that iodobenzene in step (1) is replaced by The rest of the steps and reagent amounts, reaction temperature and time, etc. are the same.

[0142] The target product 9f (a-(3,4-dimethylphenyl)methylene-5- lactone) is Yellow liquid, mass 168 mg, yield 83%. See Figure 17 and Figure 18 .

[0143] 1 H NMR (400 MHz, Chloroform-d) δ: 7.87 (t, J = 4.0 Hz 1H), 7.22-7.16 (m, 3H), 4.38 (t, J = 4.0 Hz, 2H), 2.90-2.86 (m, 2H), 2.28 (s, 6H), 2.00-1.94 (m, 2H).

[0144] 13 C NMR (101 MHz, Chloroform-d) δ: 167.4, 142.0, 138.5, 137.0, 132.7, 131.8, 129.9, 127.9, 124.6, 68.7, 26.1, 23.1, 20.0, 19.9.

[0145] HRMS (ESI) m / z: [M+H] + Calcd for C 14 H 17 O2 217.1223; Found 217.1229.

[0146] methylene-5-lactone

[0147] Example 10

[0148] Example 10 differs from Example 8 in that iodobenzene in step (1) is replaced by The remaining steps were identical in terms of reagent amounts, reaction temperatures and times, etc.

[0149] The target product 10f (a-(4-bromophenyl)methylene-5-lactone) was Yellow liquid, mass 179 mg, yield 86%. See Figure 19 and Figure 20 .

[0150] 1 H NMR (400 MHz, Chloroform-d) δ: 7.83 (t, J = 4.0 Hz, 1H), 7.53 (d, J = 12.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 4.40 (t, J = 8.0 Hz, 2H), 2.85-2.81 (m, 2H), 2.01-1.95 (m, 2H).

[0151] 13 C NMR (101 MHz, Chloroform-d) δ: 166.8, 140.4, 133.9, 131.9, 131.7, 126.5, 123.6, 68.8, 26.0, 23.0.

[0152] HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 12 BrO2 267.0015; Found 267.0021.

[0153] Example 11

[0154] Example 11 differs from Example 8 in that the iodobenzene in step (1) is replaced with The remaining steps were identical in terms of reagent amounts, reaction temperatures and times, etc.

[0155] The target product 11f (a-(4-cyanophenyl)methylene-5-lactone) was Colorless liquid, mass 173 mg, yield 81%. See Figure 21 and Figure 22 .

[0156] 1 H NMR (400 MHz, Chloroform-d) δ: 7.88 (t, J = 4.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 4.42 (t, J = 4.0 Hz, 2H), 2.87-2.83 (m, 2H), 2.02-1.97 (m, 2H).

[0157] 13 C NMR (101 MHz, Chloroform-d) δ: 166.1, 139.4, 139.3, 132.4, 130.5, 129.1, 118.5, 112.5, 69.0, 26.0, 22.9.

[0158] HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 12 NO2 214.0863; Found 214.0866.

[0159] Example 12 Preparation of a-phenyl methylene-ε-lactone

[0160]

[0161] (1) Preparation of compound 12a

[0162] A round bottom flask was charged with Cul (0.19 g), Pd(PPh3)2Cl2(0.35 g), triethylamine (30 mL) in sequence. Iodobenzene (1.23 mL, 11 mmol) was slowly added to the round bottom flask and stirring was continued for 15 min. 5-hexyn-1-ol (0.98 g, 10 mmol) was then slowly added to the round bottom flask and stirring was continued for 6 h. After disappearance of starting material was monitored by TLC, the reaction mixture was filtered and concentrated, and purified by column chromatography (eluent: petroleum ether: ethyl acetate = 4: 1, V / V) to give compound 12a (1.62 g, 93%).

[0163] (2) Preparation of compound 12b

[0164] A round bottom flask was charged with compound 12a (1.62 g, 9.31 mmol), anhydrous dichloromethane (30 mL), p-toluenesulfonic acid (TsOH-H2O, 0.17 g) in sequence under nitrogen atmosphere at 0 °C. 3,4-dihydro-2H-pyran (DHP, 0.88 g, 10.52 mmol) was then slowly added dropwise to the reaction flask and stirring was continued for 24 h. After disappearance of starting material was monitored by TLC, saturated sodium bicarbonate solution (5 mL) was slowly added to the round bottom flask to pH = 7. The reaction mixture was extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. Purification by column chromatography (eluent: petroleum ether: ethyl acetate = 20: 1, V / V) gave compound 12b (2.02 g, 84%).

[0165] (3) Preparation of compound 12c

[0166] To a round bottom flask, compound 12b (2.02 g, 7.82 mmol), anhydrous NaI (2.58 g, 17.20 mmol) and anhydrous tetrahydrofuran (30 mL) were added successively under nitrogen atmosphere at 0 °C. The reaction mixture was stirred for 10 minutes, then TMSCF3 (2.22 g, 15.64 mmol) was added slowly, and the reaction was continued at 25 °C for 24 h. After the reaction was completed, 30 mL of water was added to the system, extracted with dichloromethane (10 x 3 mL), washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The concentrated product was transferred to a round bottom flask, dichloromethane (15 mL) and SiO2 (0.95 g, 15.64 mmol) were added successively, and stirred at room temperature for 24 h. The reaction liquid was filtered, the solvent was evaporated, and column chromatography was used for separation and purification (eluent: petroleum ether: ethyl acetate = 1:1, V / V) to obtain compound 12c (1.66 g, 74%).

[0167] (4) Preparation of compound 12d

[0168] Compound 12c (1.66 g, 5.78 mmol) was dissolved in 30 mL of methanol, and macroporous resin (Amberlyst 15, 1.39 g, 10 mmol) was added. The reaction mixture was stirred for 3 h, filtered, the solvent was evaporated, and column chromatography was used for separation and purification (eluent: ethyl acetate) to obtain compound 12d (0.72 g, 62%).

[0169] (5) Preparation of compound 12f α-phenyl methylene-ε-lactone

[0170] In a Schlenk flask, compound 12d (1 mmol, 202 mg), AgBF4 (5 mmol%, 9 mg), and ethylene glycol dimethyl ether 5 mL were added. The reaction mixture was reacted at 80 °C for 20 h, the reaction mixture was concentrated, and column chromatography was used for separation and purification (eluent: petroleum ether: ethyl acetate = 4:1, V / V) to obtain 12f (α-phenyl methylene-ε-lactone).

[0171] Compound 12f (α-phenyl methylene-ε-lactone 78%, 158 mg), yellow oily liquid, mass 158 mg. See Figure 23 and Figure 24 .

[0172] 1 H NMR (400 MHz, Chloroform-d) δ: 7.39 (d, J = 4.0 Hz, 4H), 7.37-7.31 (m, 1H), 7.17 (s, 1H), 4.29 (t, J = 4.0 Hz, 2H), 2.64-2.61 (m, 2H), 1.96-1.89 (m, 4H).

[0173] 13 C NMR (101 MHz, Chloroform-d) δ: 174.2, 137.4, 135.2, 135.0, 129.4, 128.7, 128.6, 68.5, 28.3, 27.3, 25.4.

[0174] HRMS (ESI) m / z: [M+H] + Calcd for C 13 H 15 O2 203.1067; Found 203.1069.

[0175] The α-alkylene-β-lactone, α-alkylene-γ-lactone, α-alkylene-δ-lactone and α-alkylene-ε-lactone obtained by the present application can be used in food, cosmetics, detergents and perfume products, etc., to add pleasant sensory experience to them; can be used as a key intermediate for synthesis of drugs, to synthesize compounds with biological activity; can be used as an effective component of pesticides, to prevent and cure crop diseases and insect pests; can be used as a monomer or additive of high polymer materials, to prepare polymers, coatings, adhesives, etc., to improve the performance of materials, such as to enhance toughness and improve heat resistance, etc.; to prepare degradable plastics, fibers, etc.

[0176] The above is a further detailed description of the present application in combination with specific preferred embodiments, and the specific implementation of the present application should not be limited to these descriptions. For those skilled in the art to which the present application belongs, without departing from the concept of the present application, a number of simple deductions or substitutions can also be made, which should be considered as falling within the protection scope of the present application.

Claims

1. A method for preparing α-alkylene lactone compounds from cyclopropenone derivatives, characterized in that, Includes the following steps: (1) Preparation of compound a CuI, Pd(PPh3)2Cl2, triethylamine, and RI were added to a container and stirred. Then... After being added to a container and stirred to react, the mixture was filtered, concentrated, and purified by column chromatography to obtain compound a; (2) Preparation of compound b In a 0°C ice-water bath under a nitrogen atmosphere, compound a, anhydrous dichloromethane, p-toluenesulfonic acid, and 3,4-dihydro-2H-pyran were added to a container and stirred. Then, a saturated sodium bicarbonate solution was added to the container to adjust the pH to 7. The mixture was extracted, washed, dried, solvent removed, and purified by column chromatography to obtain compound b. (3) Preparation of compound c In a 0°C ice-water bath under a nitrogen atmosphere, compound b, anhydrous tetrahydrofuran, and NaI were added to a container and stirred. Then, TMSCF3 was added, and the reaction was continued at 25°C with stirring. After the reaction was completed, water was added to the container. The mixture was extracted, washed, dried, and the concentrated product after solvent removal was transferred to the container. Dichloromethane and SiO2 were added to the container, and the reaction was stirred at room temperature. The reaction solution was filtered, the solvent was evaporated, and the product was purified by column chromatography to obtain compound c. (4) Preparation of compound d Compound c was dissolved in methanol, and then macroporous resin Amberlyst 15 was added and stirred to react. The mixture was filtered, solvent removed, and purified by column chromatography to obtain compound d. (5) Preparation of compound fα-alkylene lactone Compound d, AgBF4, and ethylene glycol dimethyl ether were added to a Shrek flask and stirred at 80°C. The mixture was concentrated and purified by column chromatography to obtain the target product compound fα-alkylene lactone. Wherein, n = any one of 0, 1, 2 or 3, R is selected from phenyl or substituted phenyl, and the substituent of the substituted phenyl is selected from any one of alkoxy, halogen, alkyl or cyano groups having 1-6 carbon atoms.

2. The method according to claim 1, characterized in that: In step (1), RI and The molar ratio is 11:10; The molar ratio of CuI to Pd(PPh3)2Cl2 is 1:0.1:0.05; The molar volume ratio of triethylamine was 1 mmol: 3 mL; the eluent for column chromatography purification was petroleum ether: ethyl acetate in a volume ratio of 4:

1.

3. The method according to claim 1, characterized in that: In step (2), the molar ratio of compound a: p-toluenesulfonic acid: 3,4-dihydro-2H-pyran is 9.46:0.946:10.7; the molar volume ratio of compound a: anhydrous dichloromethane is 9.46 mmol:30 mL; and the eluent for column chromatography purification is petroleum ether: ethyl acetate in a volume ratio of 20:

1.

4. The method according to claim 1, characterized in that: In step (3), the molar ratio of compound b: NaI: TMSCF3: SiO2 is 7.59:16.7:15.2:15.2; the molar volume ratio of compound b: anhydrous tetrahydrofuran: dichloromethane is 7.59 mmol:30 mL:15 mL; the eluent for column chromatography separation and purification is petroleum ether: ethyl acetate in a volume ratio of 1:

1.

5. The method according to claim 1, characterized in that: In step (4), the molar ratio of compound c to macroporous resin Amberlyst 15 is 1:1; the molar volume ratio of compound c to methanol is 5.12 mmol: 30 mL; and the eluent for column chromatography purification is ethyl acetate.

6. The method according to claim 1, characterized in that: In step (5), the molar ratio of compound d to AgBF4 is 1:0.05; the molar volume ratio of compound d to ethylene glycol dimethyl ether is 1 mmol: 5 mL; and the eluent for column chromatography purification is petroleum ether to ethyl acetate in a volume ratio of 4:1.

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