Preparation method and application of an o-pyrazolyl phenylacetone olefin derivative

Abstract

This invention discloses a method for preparing and applying o-pyrazolylphenylacetone olefin derivatives. The method involves dispersing o-pyrazolylphenylpropenol compounds, aryl aldehyde compounds, and a catalyst in an organic solvent to react and obtain o-pyrazolylphenylacetone derivatives. The method for synthesizing o-pyrazolylphenylacetone derivatives of this invention has advantages such as inexpensive raw materials, simplicity and efficiency, mild reaction conditions, high atom economy, easy product purification, and green economy. The obtained products can be directly applied as potential drugs in the pharmaceutical field, showing broad application prospects.

Description

Technical Field

[0001] This invention relates to the field of organic compound synthesis technology, and in particular to a method for preparing and applying o-pyrazolyl phenylacetone derivatives. Background Technology

[0002] The unsaturated bonds and carbonyl groups contained in the structural units of unsaturated ketones can readily undergo transformations such as 1,4-conjugated addition and Aldol reaction. Therefore, as a class of organic synthesis building blocks with great application potential, unsaturated ketones are widely used in perfumery, biochemistry, agriculture, food chemistry, polymer materials science and other fields. For this reason, the synthesis methods of unsaturated ketones have attracted much attention in both academia and industry. Traditional methods for constructing unsaturated ketone skeletons mainly include the Witig reaction, Homer-Wadsworth-Emmons reaction, Aldol reaction and Claisen-Schmidt condensation reaction (Kreher, U.; Rosamilia, A.; Raston, C.; Scott, J.; Strauss, C.; Direct Preparation of Monoarylidene Derivatives of Aldehydes and Enolizable Ketones with DIMCARB. [J] Org. Lett. 2003, 5, 17, 3107–3110). Later, some new metal-catalyzed methods for synthesizing unsaturated ketones were developed (Wu, X.; Neumann, H.; Spannenberg, A.; Schulz, T.; Jiao, H.; Beller, M. Development of a General Palladium-Catalyzed Carbonylative Heck Reaction of Aryl Halides. [J] J. Am. Chem. Soc. 2010, 132, 41, 14596–14602).

[0003] o-Pyrazolylphenylacetone derivatives hold great promise as potential drug and natural product backbones. Pyrazol derivatives exhibit antimicrobial, antitumor, antiviral, antituberculosis, antimalarial, antidiabetic, antidiuretic, anticonvulsant, antidepressant, antiobesity, and antipyretic effects. Therefore, developing a synthetic method for o-Pyrazolylphenylacetone derivatives that offers advantages such as inexpensive raw materials, simplicity and efficiency, mild reaction conditions, high atom economy, easy product purification, and green economic benefits is of great significance. Summary of the Invention

[0004] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a method for preparing and applying o-pyrazolyl phenylacetone derivatives.

[0005] The technical solution adopted in this invention is:

[0006] A method for preparing an o-pyrazolyl phenylacetone olefin derivative includes the following steps:

[0007] An o-pyrazole phenylpropenol compound, an aryl aldehyde compound, and a catalyst were dispersed in an organic solvent and reacted to obtain an o-pyrazole phenylacetone derivative; the structural formula of the o-pyrazole phenylpropenol compound is shown in Formula A; the structural formula of the aryl aldehyde compound is CHO-R. 6 The structure of the o-pyrazolyl phenylacetone olefin derivative is shown in Formula B:

[0008]

[0009] Among them, R 1 Selected from methyl, -H, R 2 Selected from one of -H, methoxy, and methyl, R 3 Selected from -H, methyl, halogen, -CF3, R 4 Selected from -H, methyl, R 5 Selected from -H, methyl, R 6 The catalyst is selected from one of 4-methylphenyl, phenyl, 4-halophenyl, 4-CF3phenyl, 2-fluoro-5-CF3phenyl, 4-methoxyphenyl, 2-methylphenyl, 2-fluorophenyl, 3-methylphenyl, 3-bromo-4-methylphenyl, 4-tert-butylphenyl, 2-naphthyl, 2-thienyl, 2-furanyl, and 2-fluoro-5-methylphenyl; the catalyst is manganese pentacarbonyl bromide (I).

[0010] Preferably, the organic solvent is diethylene glycol dimethyl ether.

[0011] Preferably, the molar ratio of the o-pyrazole benzene propenol compound and the catalyst is 1:0.1 to 0.2.

[0012] More preferably, the molar ratio of the o-pyrazole benzene propenol compound and the catalyst is 1:0.2.

[0013] Preferably, the molar ratio of the enol compound to the organic solvent is 1:6 to 8.

[0014] Preferably, the molar ratio of the o-pyrazole benzene propenol compound and the aryl aldehyde compound is 1:2 to 3.

[0015] Preferably, the reaction further includes the addition of a Lewis acid;

[0016] More preferably, the Lewis acid includes zinc bromide, magnesium oxide, and dimethyl zinc;

[0017] More preferably, the molar ratio of zinc bromide, magnesium oxide, dimethyl zinc to o-pyrazole benzene propenol is 0.8-1.2:0.8-1.2:0.8-1.2:1.

[0018] Preferably, the reaction temperature is 90℃~110℃.

[0019] Preferably, the reaction time is 4h to 12h.

[0020] Preferably, the o-pyrazolyl phenylacetone derivative is separated and purified by column chromatography.

[0021] More preferably, the eluent used in the column chromatography is composed of petroleum ether and ethyl acetate.

[0022] The above preparation method is applied to the preparation of 1,5-diphenyl-3-carbonyl-1-pentene compounds. The o-pyrazolyl phenylacetone olefin derivative prepared by the above preparation method is depyrazolized (see references for depyrazolization: ChemAsian J. 2020, 15, 1941–1944; J.Am.Chem.Soc. 2020, 142, 7345-7349) to obtain 1,5-diphenyl-3-carbonyl-1-pentene compounds (see reference for product: NATURE COMMUNICATIONS (2020) 11: 1956).

[0023] The beneficial effects of this invention are:

[0024] The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives of the present invention has the advantages of inexpensive raw materials, simplicity and efficiency, mild reaction conditions, high atom economy, easy product purification, and green economy. The obtained product can be directly applied to the pharmaceutical field as a potential drug, and has broad application prospects. Attached Figure Description

[0025] Figure 1 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 1.

[0026] Figure 2 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 1.

[0027] Figure 3 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 2.

[0028] Figure 4 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 2.

[0029] Figure 5 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 3.

[0030] Figure 6 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 3.

[0031] Figure 7 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 4.

[0032] Figure 8 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 4.

[0033] Figure 9 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 5.

[0034] Figure 10 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 5.

[0035] Figure 11 The image shows the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 6.

[0036] Figure 12 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 6.

[0037] Figure 13 The above is the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 7.

[0038] Figure 14 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 7.

[0039] Figure 15 The above is the 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 8.

[0040] Figure 16 The image shows the carbon NMR spectrum of the o-pyrazolyl phenylacetone derivative of Example 8. Detailed Implementation

[0041] The following will describe the concept and technical effects of the present invention clearly and completely with reference to the embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention. Unless otherwise specified, the experimental methods used in the embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available.

[0042] In the description of this invention, the terms "one embodiment," "some embodiments," "illustrative embodiment," "example," "specific example," or "some examples," etc., refer to specific features, structures, materials, or characteristics described in connection with that embodiment or example, which are included in at least one embodiment or example of the invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples.

[0043] The o-pyrazole phenylpropenols in Examples 1-8 were prepared according to the following method (Reference: Yang, C.; Zhou, X.; Shen, L.; Ke, Z.; Jiang, H.; Zeng, W. Mn(I)-catalyzed sigmatropic rearrangement of β,γ-unsaturated alcohols. [J] Nat Commun 2023, 14, 1862). 1.0 mmol of o-pyrazole phenylpropenone and 10 mL of anhydrous tetrahydrofuran (THF) were added to a three-necked round-bottom flask and dissolved in an argon atmosphere. The solution was then cooled to 0°C, and 2.0 mL of a 1.0 mol / L Grignard reagent THF solution was added dropwise. After the addition was complete, the temperature was raised to room temperature and stirred overnight. The reaction was then quenched with saturated NH4Cl solution, and the reaction solution was extracted three times with ethyl acetate (10 mL of ethyl acetate each time). The organic layers were combined and then treated with anhydrous Na2Cl. The product was dried with SO4, and the solvent was evaporated under vacuum to obtain the crude product. This crude product was then rapidly purified by separation on a silica gel column using petroleum ether / ethyl acetate (volume ratio 10:1–5:1) to obtain o-pyrazole benzene propenols. The reaction formula is as follows:

[0044]

[0045] Example 1:

[0046] 21.4 g (0.1 mmol) of o-pyrazolylphenylpropenol, 24 mg (0.2 mmol) of p-methylbenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 22 mg of the o-pyrazolylphenylacetone derivative (yield: 69%).

[0047] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 1 As shown, the carbon NMR spectrum is as follows: Figure 2 As shown.

[0048] Spectral analysis:

[0049] 1 H NMR (500MHz, DMSO) δ8.04(d,J=1.7Hz,1H),7.72(s,1H),7.57(d,J=7.9Hz,2H),7.51(d,J=16.3Hz,1H),7.47(d,J=7.6Hz,1H),7.41(s,1H),7 .39–7.31(m,2H),7.24(d,J=7.9Hz,2H),6.74(d,J=16.3Hz,1H),6.50(d,J=1.7Hz,1H),2.88–2.83(m,2H),2.81–2.75(m,2H).,2.33(s,3H).

[0050] 13 C NMR (126MHz, DMSO) δ199.27,142.70,140.95,140.61,139.95,137.30,132.10,132.04, 130.93,130.05,128.99,128.88,127.44,126.76,125.74,106.91,41.07,26.09,21.51.

[0051] HR-MS: Theoretical value [M+H] + :C 21 H 20 N2O: 317.1648, measured value: 317.1652.

[0052] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0053]

[0054] Example 2:

[0055] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0056] 21.4 g (0.1 mmol) of o-pyrazolylphenylpropenol, 21 mg (0.2 mmol) of benzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 16 mg of the o-pyrazolylphenylacetone derivative (yield: 53%).

[0057] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 3 As shown, the carbon NMR spectrum is as follows: Figure 4 As shown.

[0058] Spectral analysis:

[0059] 1 H NMR (500MHz, CDCl3) δ7.73(d,J=1.3Hz,1H),7.64(d,J=2.2Hz,1H),7.51(d,J=3.8Hz,1H),7.48(d,J=16.1Hz,2H),7.41–7.3 5(m,5H),7.32–7.29(m,2H),6.64(d,J=16.2Hz,1H),6.46(t,J=2.0Hz,1H),2.92(dd,J=12.6,5.1Hz,2H),2.88–2.83(m,2H).

[0060] 13 C NMR (126MHz, CDCl3) δ199.46,142.86,140.47,139.77,137.42,134.52,130.81,130. 79,130.48,128.95,128.89,128.28,127.12,126.63,126.12,106.55,41.61,26.58.

[0061] HR-MS: Theoretical value [M+H] + :C 20 H18 N2O: 303.1492, Measured value: 303.1487.

[0062] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0063]

[0064] Example 3:

[0065] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0066] 21.4 g (0.1 mmol) of o-pyrazolylphenylpropenol, 28 mg (0.2 mmol) of p-chlorobenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, and evaporated to dryness. The mixture was then purified by column chromatography, with the eluent consisting of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 26 mg of the o-pyrazolylphenylacetone derivative (yield: 77%).

[0067] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 5 As shown, the carbon NMR spectrum is as follows: Figure 6 As shown.

[0068] Spectral analysis:

[0069] 1 H NMR (500MHz, DMSO) δ8.07(s,1H),7.75(d,J=7.8Hz,3H),7.58(d,J=16.4Hz,1H),7.54–7.49(m,3H),7.45(t,J=7 .2Hz, 1H), 7.39 (d, J = 9.2Hz, 2H), 6.86 (d, J = 16.3Hz, 1H), 6.54 (s, 1H), 2.94–2.89 (m, 2H), 2.84 (d, J = 7.5Hz, 2H).

[0070] 13C NMR (126MHz, DMSO) δ199.28,141.22,140.63,139.94,137.22,135.40,133.85,132. 03,130.94,130.56,129.47,128.98,127.46,127.33,126.75,106.93,41.24,25.99.

[0071] HR-MS: Theoretical value [M+H] + :C 20 H 17 ClN2O: 337.1102, Measured value: 337.1098.

[0072] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0073]

[0074] Example 4:

[0075] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0076] 21.4 g (0.1 mmol) of o-pyrazolylphenylpropenol, 27 mg (0.2 mmol) of p-methoxybenzaldehyde, 5.5 mg (0.02 mmol) of pentacarbonylmanganese bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 23 mg of the o-pyrazolylphenylacetone derivative (yield: 70%).

[0077] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 7 As shown, the carbon NMR spectrum is as follows: Figure 8 As shown.

[0078] Spectral analysis:

[0079] 1H NMR (500MHz, DMSO) δ8.08(d,J=1.7Hz,1H),7.76(s,1H),7.61(d,J=7.9Hz,2H),7.54(d,J=16.3Hz,1H),7.51(d,J=7.6Hz,1H),7.45(s,1H), 7.41–7.35(m,2H),7.27(d,J=7.9Hz,2H),6.78(d,J=16.3Hz,1H),6.54(d,J=1.7Hz,1H),2.92–2.87(m,2H),2.85–2.79(m,2H),2.37(s,3H).

[0080] 13 C NMR (126MHz, DMSO) δ199.27,142.70,140.95,140.61,139.95,137.30,132.10,132.04, 130.93,130.05,128.99,128.88,127.44,126.76,125.74,106.91,41.07,26.09,21.51.

[0081] HR-MS: Theoretical value [M+H] + :C 21 H 20 N2O2: 333.1598, Measured value: 333.1596.

[0082] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0083]

[0084] Example 5:

[0085] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0086] 23 mg (0.1 mmol) of 4-methyl-o-pyrazolylphenylpropenol, 24 mg (0.2 mmol) of p-methylbenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 17.5 mg of the o-pyrazolylphenylacetone derivative (yield: 53%).

[0087] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 9 As shown, the carbon NMR spectrum is as follows: Figure 10 As shown.

[0088] Spectral analysis:

[0089] 1 H NMR (500MHz, DMSO) δ8.01(d,J=2.2Hz,1H),7.73(s,1H),7.61(d,J=8.0Hz,2H),7.54(d,J=16.3Hz,1H),7.31(s,1H),7.27(d,J=7.9Hz,2H),7.2 4(d,J=8.0Hz,1H),7.20(s,1H),6.77(d,J=16.3Hz,1H),6.51(d,J=1.8H z,1H),2.89–2.84(m,2H),2.80–2.73(m,2H),2.38(s,3H),2.36(s,3H).

[0090] 13 C NMR (126MHz, DMSO) δ199.29,142.68,140.93,140.43,138.42,137.61,137.05,132.11,131.9 8,131.33,130.05,128.86,127.87,126.61,125.75,106.75,41.16,26.05,21.50,21.13(s).

[0091] HR-MS: Theoretical value [M+H] + :C 22 H 22 N2O: 331.1805, measured value: 331.1798.

[0092] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0093]

[0094] Example 6:

[0095] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0096] 25 mg (0.1 mmol) of 4-chloro-o-pyrazolylphenylpropenol, 24 mg (0.2 mmol) of p-methylbenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 30 mg of the o-pyrazolylphenylacetone derivative (yield: 85%).

[0097] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 11 As shown, the carbon NMR spectrum is as follows: Figure 12 As shown.

[0098] Spectral analysis:

[0099] 1 H NMR (500MHz, DMSO) δ8.09(d,J=2.1Hz,1H),7.77(d,J=1.3Hz,1H),7.62(t,J=5.6Hz,3H),7.57(d,J=16.3Hz,1H),7.46(dd,J=8.4,2.3Hz,1H),7 .41(d,J=8.4Hz,1H),7.27(d,J=7.9Hz,2H),6.78(d,J=16.3Hz,1H),6.55(t,J=2.0Hz,1H),2.96–2.90(m,2H),2.85–2.80(m,2H),2.36(s,3H).

[0100] 13 C NMR (126MHz, DMSO) δ199.04,142.82,140.97,139.66,138.79,133.22,132.19,132. 10,130.64,130.05,128.88,128.47,127.34,125.70,107.20,40.61,25.85,21.51.

[0101] HR-MS: Theoretical value [M+H] + :C 21 H 19 ClN2O: 351.1259, Measured value: 351.1253.

[0102] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0103]

[0104] Example 7:

[0105] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0106] 25 mg (0.1 mmol) of 5-methoxy-o-pyrazolylphenylpropenol, 24 mg (0.2 mmol) of p-methylbenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, evaporated to dryness, and purified by column chromatography. The eluent consisted of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 17 mg of the o-pyrazolylphenylacetone derivative (yield: 50%).

[0107] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 13 As shown, the carbon NMR spectrum is as follows: Figure 14 As shown.

[0108] Spectral analysis:

[0109] 1 H NMR(500MHz,DMSO)δ8.09(d,J=2.2Hz,1H),7.76(d,J=1.3Hz,1H),7.60(d,J=8.0H z,2H),7.53(d,J=16.3Hz,1H),7.40(d,J=8.5Hz,1H),7.27(d,J=7.9Hz,2H),7.03( dd,J=8.5,2.6Hz,1H),6.94(d,J=2.6Hz,1H),6.77(d,J=16.3Hz,1H),6.54(t,J=2 .0Hz,1H),3.82(s,3H),2.83(d,J=7.8Hz,2H),2.79(d,J=7.5Hz,2H),2.36(s,3H).

[0110] 13C NMR (126MHz, DMSO) δ199.42,158.37,142.61,140.92,140.60,140.51,132.10,131.99,131.80, 130.04,128.86,128.81,125.76,125.76,114.83,111.97,106.91,55.90,41.36,25.55,21.49.

[0111] HR-MS: Theoretical value [M+H] + :C 22 H 22 N2O2: 347.1754, Measured value: 347.1745.

[0112] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0113]

[0114] Example 8:

[0115] A method for synthesizing o-pyrazolyl phenylacetone olefin derivatives, comprising the following steps:

[0116] 23 mg (0.1 mmol) of o-(4-methylpyrazol)phenylpropenol, 24 mg (0.2 mmol) of p-methylbenzaldehyde, 5.5 mg (0.02 mmol) of manganese pentacarbonyl bromide (I), 22 mg (0.1 mmol) of zinc bromide, 4 mg (0.1 mmol) of magnesium oxide, 9.5 mg (0.1 mmol) of dimethyl zinc, and 0.1 mL of diethylene glycol dimethyl ether (analytical grade) were added to a Schlack tube under an argon atmosphere. The mixture was stirred at 100 °C for 4 h, cooled to room temperature, and evaporated to dryness. The mixture was then purified by column chromatography, with the eluent consisting of petroleum ether and ethyl acetate in a volume ratio of 10:1, yielding 14 mg of the o-pyrazolylphenylpropenone derivative (yield: 43%).

[0117] The 1H NMR spectrum of the o-pyrazolyl phenylacetone derivative in this embodiment is as follows: Figure 15 As shown, the carbon NMR spectrum is as follows: Figure 16 As shown.

[0118] Spectral analysis:

[0119] 1H NMR (500MHz, DMSO) δ7.79(s,1H),7.57(d,J=8.0Hz,2H),7.51(d,J=14.8Hz,2H),7.45(d,J=7.5Hz,1H),7.38(td,J=7.4,1.4Hz,1H),7.33(td,J=7.5,1 .3Hz,1H),7.29(dd,J=7.7,1.2Hz,1H),7.24(d,J=8.0Hz,2H),6.75(d,J=16 .3Hz,1H),2.90–2.85(m,2H),2.83–2.78(m,2H),2.33(s,3H),2.09(s,3H).

[0120] 13 C NMR (126MHz, DMSO) δ199.36,142.68,141.20,140.94,140.06,137.05,132.11,130.92,130 .43,130.05,128.87,128.67,127.38,126.52,125.75,116.59,41.18,26.16,21.50,9.12.

[0121] HR-MS: Theoretical value [M+H] + :C 22 H 22 N2O: 331.1805, measured value: 331.1798.

[0122] In summary, the structural formula of the o-pyrazolyl phenylacetone derivative of this embodiment is as follows:

[0123]

[0124] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for preparing an o-pyrazolyl phenylacetone olefin derivative, characterized in that, Includes the following steps: An o-pyrazole phenylpropenol compound, an aryl aldehyde compound, and a catalyst were dispersed in an organic solvent and reacted to obtain o-pyrazole phenylacetone olefin derivatives; the structural formula of the o-pyrazole phenylpropenol compound is shown in Formula A; the structural formula of the aryl aldehyde compound is CHO-R. 6 The structure of the o-pyrazolyl phenylacetone olefin derivative is shown in Formula B: Among them, R 1 Selected from methyl, -H, R 2 Selected from one of -H, methoxy, and methyl, R 3 Selected from -H, methyl, halogen, -CF3, R 4 Selected from -H, methyl, R 5 Selected from -H, methyl, R 6 The compound is selected from one of 4-methylphenyl, phenyl, 4-halophenyl, 4-CF3phenyl, 2-fluoro-5-CF3phenyl, 4-methoxyphenyl, 2-methylphenyl, 2-fluorophenyl, 3-methylphenyl, 3-bromo-4-methylphenyl, 4-tert-butylphenyl, 2-naphthyl, 2-thienyl, 2-furanyl, and 2-fluoro-5-methylphenyl; the catalyst is manganese pentacarbonyl bromide (I); the reaction also includes a Lewis acid; the Lewis acid includes zinc bromide, magnesium oxide, and dimethylzinc; the molar ratio of zinc bromide, magnesium oxide, dimethylzinc to o-pyrazole benzene propenol is 0.8~1.2:0.8~1.2:0.8~1.2:

1.

2. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The organic solvent is diethylene glycol dimethyl ether.

3. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The molar ratio of the o-pyrazole benzene propenol compound and the catalyst is 1:0.1~0.

2.

4. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The molar ratio of the o-pyrazole benzene propenol compound and the organic solvent is 1:6 to 8.

5. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The molar ratio of the o-pyrazole benzene propenols and aryl aldehydes is 1:2 to 3.

6. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The reaction temperature is 90℃~110℃, and the reaction time is 4h~12h.

7. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 1, characterized in that: The o-pyrazolyl phenylacetone derivatives were separated and purified by column chromatography.

8. The method for synthesizing o-pyrazolyl phenylacetone olefin derivatives according to claim 7, characterized in that: The column chromatography uses an eluent composed of petroleum ether and ethyl acetate.

9. The use of the preparation method according to any one of claims 1-8 in the preparation of 1,5-diphenyl-3-carbonyl-1-pentene compounds, characterized in that, The o-pyrazolyl phenylacetone derivative prepared by the preparation method according to any one of claims 1-8 is depyrazolized to obtain 1,5-diphenyl-3-carbonyl-1-pentene compounds.

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