Synthesis method of oxazoline compound

Abstract

The invention belongs to the technical field of organic chemistry, and particularly discloses a synthesis method of an oxazoline compound, which comprises the following steps: S1, sequentially adding magneton, an olefin compound, an amide compound, electrolyte and an iodine catalyst into a three-neck bottle, and mixing; s2, after mixing is completed, a carbon rod electrode is assembled to serve as a positive electrode, and a nickel sheet electrode is assembled to serve as a negative electrode; s3, carrying out an addition reaction under a power-on condition; and S4, after the addition reaction is finished, removing the organic solvent, and purifying the obtained product to obtain the oxazoline compound. By adopting the synthesis method of the oxazoline compound, the invention provides a convenient method for cyclizing and synthesizing the oxazoline compound from olefin and amide under mild reaction conditions, and an oxidizing agent and alkali do not need to be additionally added.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemistry, and specifically relates to a method for synthesizing an oxazoline compound. Background Art

[0002] Olefins and amides are two cheap and readily available chemical raw materials, so it is undoubtedly very valuable to achieve high-value conversion of amides and olefins. Oxazoline compounds are widely used in medicine, pesticides and chiral ligands. As early as the last century, the cyclization reaction of β-amino alcohols was the most common method for synthesizing oxazoline compounds. However, β-amino alcohols need to be pre-synthesized and are expensive, which limits the application of this method. In recent years, the ammoxidation of olefins has become a new way to synthesize oxazoline compounds. It does not require pre-functionalization, has step economy, and is a more attractive strategy. In 2007, Professor Satoshi Minakata's research group used equivalent oxidants and iodine reagents to achieve the cyclization reaction of olefins and amides to construct oxazoline compounds. In 2021, Professor Wei Li's research group used additional bases or Lewis acids to regulate the nucleophilicity of benzamide to achieve site-selective ammoxidation of olefins to construct oxazoline compounds. In 2022, Professor Lei Aiwen used electrochemical means to achieve the cyclization of indene and amide to construct oxazoline compounds. In the current cyclization reaction of olefins and amides, an additional oxidant needs to be added. The substrate is limited and can only be applied to olefins with lower oxidation potentials. The reaction of simple olefins with higher oxidation potentials is still difficult to achieve.

[0003] Therefore, there is a need in the art to develop a method for synthesizing oxazoline compounds that can effectively solve the above problems. Summary of the invention

[0004] The purpose of the present invention is to provide a method for synthesizing an oxazoline compound, and to provide a method for synthesizing an oxazoline compound by cyclization of olefins and amides under mild reaction conditions and conveniently without the need for adding an external oxidant and a base.

[0005] To achieve the above object, the present invention provides a method for synthesizing an oxazoline compound, comprising the following steps:

[0006] Step S1, sequentially adding a magnetic particle, an olefin compound, an amide compound, an electrolyte, and an iodine catalyst into a three-necked flask and mixing them;

[0007] Step S2, after the mixing is completed, a carbon rod electrode is provided as a positive electrode and a nickel sheet electrode is provided as a negative electrode;

[0008] Step S3, performing an addition reaction under the condition of power on;

[0009] Step S31, pumping the system to a nitrogen atmosphere, then adding an organic solvent so that the organic solution covers the electrode;

[0010] Step S32, reacting for 4-5 hours at a current of 8-12 mA and a temperature of 60-80° C.;

[0011] Step S4, after the addition reaction is completed, the organic solvent is removed, and the obtained product is purified to obtain an oxazoline compound;

[0012] Step S41, removing the remaining organic solvent by distillation under reduced pressure;

[0013] Step S42: Purify the product obtained in step S41 by column chromatography and elute with a mixture of petroleum ether and ethyl acetate as an eluent to obtain an oxazoline compound.

[0014] Preferably, the olefin compound is a styrene compound, which is a styrene having electron-withdrawing or electron-donating substituents at the ortho-, meta- or para-positions on the benzene ring.

[0015] Preferably, the olefin compound is one of styrene substituted with halogen at positions 2, 3, and 4; styrene substituted with methyl at positions 2, 3, and 4; styrene substituted with methoxy at positions 2, 3, and 4; and styrene substituted with trifluoromethyl at positions 2, 3, and 4.

[0016] Preferably, the amide compound is a benzamide compound, which has an electron-withdrawing or electron-donating substituent at the ortho-, meta- or para-position on the benzene ring.

[0017] Preferably, the amide compound is one of benzamide substituted with halogen at positions 2, 3, and 4; benzamide substituted with methyl at positions 2, 3, and 4; and benzamide substituted with methoxy at positions 2, 3, and 4.

[0018] Preferably, in step S1, the amount of the olefin compound used is 0.3-0.8 mmol; the amount of the amide compound used is 1-1.5 mmol.

[0019] Preferably, in step S1, the organic solvent is 1,2-dichloroethane, and the amount thereof is 8-12 mL; the electrolyte is tetrabutylammonium hexafluorophosphate, and the amount thereof is 0.3-1 mmol; and the iodine catalyst is sodium iodide, and the amount thereof is 0.03-0.10 mmol.

[0020] Preferably, in step S42, column chromatography is performed using silica gel with a standard particle size of 200-300 mesh for purification; and the volume ratio of petroleum ether to ethyl acetate added is 1:1 to 10:1.

[0021] The present invention adopts the above-mentioned method for synthesizing an oxazoline compound, and the beneficial effects are as follows:

[0022] (1) The present invention provides a method for synthesizing oxazoline compounds by cyclization of olefins and amides under mild reaction conditions and conveniently, and does not require the addition of external oxidants and bases, making the reaction more inexpensive;

[0023] (2) The method of the present invention has a wide range of raw materials to choose from, and utilizes the cyclization reaction of cheap and readily available olefins and amides to construct oxazoline compounds, which can solve the problem in the prior art that some simple olefins such as styrene cannot react.

[0024] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The present invention is a flow chart of an embodiment of a method for synthesizing an oxazoline compound. DETAILED DESCRIPTION

[0026] The technical solution of the present invention is further described below through the accompanying drawings and embodiments.

[0027] Unless otherwise defined, technical or scientific terms used in the present invention shall have the common meanings understood by one having ordinary skills in the field to which the present invention belongs.

[0028] like Figure 1 As shown, a method for synthesizing an oxazoline compound comprises the following steps:

[0029] Step S1, sequentially add a magnetic particle, 0.3-0.8 mmol of an olefin compound, 1-1.5 mmol of an amide compound, 0.3-1 mmol of an electrolyte, and 0.03-0.10 mmol of an iodine catalyst into a three-necked flask and mix them.

[0030] The olefin compound is a styrene compound, which is a styrene having electron-withdrawing or electron-donating substituents at the ortho-position, meta-position or para-position on the benzene ring.

[0031] The olefin compound is specifically one of styrene substituted with halogen at position 2, 3, or 4, styrene substituted with methyl at position 2, 3, or 4, styrene substituted with methoxy at position 2, 3, or 4, and styrene substituted with trifluoromethyl at position 2, 3, or 4.

[0032] The amide compound is a benzamide compound, which has an electron-withdrawing or electron-donating substituent at the ortho, meta, or para position on the benzene ring.

[0033] The amide compound is specifically one of benzamide substituted with halogen at position 2, 3, or 4, benzamide substituted with methyl at position 2, 3, or 4, and benzamide substituted with methoxy at position 2, 3, or 4.

[0034] The organic solvent is 1,2-dichloroethane, the electrolyte is tetrabutylammonium hexafluorophosphate, and the iodine catalyst is sodium iodide.

[0035] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0036] Step S3, performing addition reaction under the condition of power on.

[0037] Step S31, pumping the system to a nitrogen atmosphere, then adding 8-12 mL of an organic solvent so that the organic solution covers the electrode, the organic solvent being 1,2-dichloroethane.

[0038] Step S32, react for 4-5 hours at a current of 8-12 mA and a temperature of 60-80°C.

[0039] Step S4: After the addition reaction is completed, the organic solvent is removed, and the obtained product is purified to obtain an oxazoline compound.

[0040] Step S41, removing the remaining organic solvent by distillation under reduced pressure.

[0041] Step S42: Purify the product obtained in step S41 by column chromatography, wherein the column chromatography uses silica gel with a standard particle size of 200-300 mesh for purification, and uses a mixture of petroleum ether and ethyl acetate as an eluent for elution, wherein the volume ratio of petroleum ether to ethyl acetate is 1:1 to 10:1, to obtain an oxazoline compound.

[0042] Embodiment 1

[0043] A method for synthesizing 2,5-diphenyl-4,5-dihydrooxazole comprises the following steps:

[0044] Step S1, add a magnetic particle, 0.5 mmol styrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0045] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0046] Step S3, performing addition reaction under the condition of power on.

[0047] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0048] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0049] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0050] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0051] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 2,5-diphenyl-4,5-dihydrooxazole 70.4 mg was obtained by separation, and the yield was 63%.

[0052] The structural formula of 2,5-diphenyl-4,5-dihydrooxazole is:

[0053] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.14–7.98(m,2H),7.54–7.48(m,1H),7.47–7.41(m,2H),7.38–7.27(m,5H),5 .39(dd,J=10.1,8.2Hz,1H), 4.79(dd,J=10.1,8.4Hz,1H), 4.28(t,J=8.3Hz,1H).

[0054] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :224.1065.

[0055] Embodiment 2

[0056] A method for synthesizing 5-(4-(tert-butyl)phenyl)-2-phenyl-4,5-dihydrooxazole comprises the following steps:

[0057] Step S1, add a magnetic particle, 0.5 mmol 4-tert-butylstyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0058] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0059] Step S3, performing addition reaction under the condition of power on.

[0060] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0061] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0062] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0063] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0064] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 5-(4-(tert-butyl)phenyl)-2-phenyl-4,5-dihydrooxazole 85.2 mg was obtained by separation, and the yield was 61%.

[0065] The structural formula of 5-(4-(tert-butyl)phenyl)-2-phenyl-4,5-dihydrooxazole is:

[0066]

[0067] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.17–8.06(m,2H),7.57–7.52(m,1H),7.51–7.41(m,5H),7.31–7.28(m,1H),5.40(dd ,J=10.0,8.2Hz,1H),4.82(dd,J=10.1,8.4Hz,1H),4.35(t,J=8.3Hz,1H),1.35(s,9H).

[0068] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :280.1696.

[0069] Embodiment 3

[0070] The synthesis method of 5-(4-fluorophenyl)-2-phenyl-4,5-dihydrooxazole comprises the following steps:

[0071] Step S1, add a magnetic particle, 0.5 mmol 4-fluorostyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0072] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0073] Step S3, performing addition reaction under the condition of power on.

[0074] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0075] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0076] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0077] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0078] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 5-(4-fluorophenyl)-2-phenyl-4,5-dihydrooxazole (67.5 mg) was obtained by separation, and the yield was 56%.

[0079] The structural formula of 5-(4-fluorophenyl)-2-phenyl-4,5-dihydrooxazole is:

[0080]

[0081] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.15–7.94(m,2H),7.56–7.41(m,3H),7.31–7.24(m,2H),7.09–6.98(m,2H),5 .37(dd,J=10.0,8.2Hz,1H), 4.79(dd,J=10.1,8.5Hz,1H), 4.23(t,J=8.3Hz,1H).

[0082] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :241.0903.

[0083] Embodiment 4

[0084] A method for synthesizing 2-phenyl-5-(3-methylphenyl)-4,5-dihydrooxazole comprises the following steps:

[0085] Step S1, add a magnetic particle, 0.5 mmol 3-methylstyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0086] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0087] Step S3, performing addition reaction under the condition of power on.

[0088] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0089] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0090] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0091] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0092] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 2-phenyl-5-(3-methylphenyl)-4,5-dihydrooxazole (67.5 mg) was obtained by separation, and the yield was 56%.

[0093] The structural formula of 2-phenyl-5-(3-methylphenyl)-4,5-dihydrooxazole is:

[0094] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.12–7.91(m,2H),7.55–7.40(m,3H),7.27–7.22(m,1H),7.14–7.07(m,3H),5.35(dd ,J=10.1,8.3Hz,1H),4.78(dd,J=10.1,8.4Hz,1H),4.27(t,J=8.3Hz,1H),2.34(s,3H).

[0095] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :238.1224.

[0096] Embodiment 5

[0097] A method for synthesizing 2-phenyl-5-(3-fluorophenyl)-4,5-dihydrooxazole comprises the following steps:

[0098] Step S1, add a magnetic particle, 0.5 mmol 3-fluorostyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0099] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0100] Step S3, performing addition reaction under the condition of power on.

[0101] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0102] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0103] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0104] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0105] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 2-phenyl-5-(3-fluorophenyl)-4,5-dihydrooxazole 59.1 mg was obtained by separation, and the yield was 52%.

[0106] The structural formula of 2-phenyl-5-(3-fluorophenyl)-4,5-dihydrooxazole is:

[0107] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.11–7.94(m,2H),7.55–7.41(m,3H),7.35(td,J=7.9,5.8Hz,1H),7.14–6.98(m,3H),5 .66(dd,J=10.1,7.8Hz,1H), 4.50(dd,J=14.8,10.2Hz,1H), 3.97(dd,J=14.8,7.8Hz,1H).

[0108] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :242.0976.

[0109] Embodiment 6

[0110] A method for synthesizing 5-(2-chlorophenyl)-2-phenyl-4,5-dihydrooxazole comprises the following steps:

[0111] Step S1, in a 25 mL three-necked flask, magnetic particles, 0.5 mmol 2-chlorostyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide were added in sequence and mixed.

[0112] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0113] Step S3, performing addition reaction under the condition of power on.

[0114] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0115] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0116] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0117] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0118] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 5-(2-chlorophenyl)-2-phenyl-4,5-dihydrooxazole (45.2 mg) was obtained by separation, and the yield was 40%.

[0119] The structural formula of 5-(2-chlorophenyl)-2-phenyl-4,5-dihydrooxazole is:

[0120] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.14–8.00(m,2H),7.59–7.34(m,5H),7.28–7.22(m,2H),5.98(dd,J=10. 2,7.6Hz,1H), 4.62(dd,J=15.0,10.2Hz,1H), 3.88(dd,J=15.0,7.5Hz,1H).

[0121] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :258.0675.

[0122] Embodiment 7

[0123] A method for synthesizing 2-phenyl-5-(2-methylphenyl)-4,5-dihydrooxazole comprises the following steps:

[0124] Step S1, in a 25 mL three-necked flask, magnetic particles, 0.5 mmol 2-methylstyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide were added in sequence and mixed.

[0125] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0126] Step S3, performing addition reaction under the condition of power on.

[0127] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0128] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0129] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0130] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0131] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 2-phenyl-5-(2-methylphenyl)-4,5-dihydrooxazole 48.4 mg was obtained by separation, and the yield was 43%.

[0132] The structural formula of 2-phenyl-5-(2-methylphenyl)-4,5-dihydrooxazole is:

[0133] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.14–7.96(m,2H),7.55–7.42(m,3H),7.34–7.30(m,1H),7.22–7.15(m,3H),5.60(dd ,J=10.2,8.5Hz,1H),4.84(dd,J=10.2,8.2Hz,1H),4.14(t,J=8.3Hz,1H),2.35(s,3H).

[0134] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :238.1220.

[0135] Embodiment 8

[0136] A method for synthesizing 5-(mesitylenetrimethylphenyl)-2-phenyl-4,5-dihydrooxazole comprises the following steps:

[0137] Step S1, add a magnetic particle, 0.5 mmol 2,4,5-trimethylstyrene, 1.5 mmol benzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0138] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0139] Step S3, performing addition reaction under the condition of power on.

[0140] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0141] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0142] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0143] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0144] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 5-(mesitylene-trimethylphenyl)-2-phenyl-4,5-dihydrooxazole (67.5 mg) was obtained by separation, and the yield was 56%.

[0145] The structural formula of 5-(s-trimethylphenyl)-2-phenyl-4,5-dihydrooxazole is:

[0146]

[0147] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3)δ8.13–7.89(m,2H),7.55–7.35(m,3H),6.84(s,2H),5.82(t,1H),4.76(dd, J=11.3,8.4Hz,1H),4.29(dd,J=10.0,8.4Hz,1H),2.31(s,6H),2.25(s,3H).

[0148] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :265.1467.

[0149] Embodiment 9

[0150] A method for synthesizing 2-4-(methoxyphenyl)-4,5-diphenyl-4,5-dihydrooxazole comprises the following steps:

[0151] Step S1, add a magnetic particle, 0.5 mmol 1,2-diphenylethylene, 1.5 mmol p-methoxybenzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0152] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0153] Step S3, performing addition reaction under the condition of power on.

[0154] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0155] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0156] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0157] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0158] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 2-4-(methoxyphenyl)-4,5-diphenyl-4,5-dihydrooxazole 118.5 mg was obtained by separation, and the yield was 72%.

[0159] The structural formula of 2-4-(methoxyphenyl)-4,5-diphenyl-4,5-dihydrooxazole is:

[0160]

[0161] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.26–8.16(m,2H),7.49–7.34(m,6H),7.27–7.13(m,6H),5.48(d,J=7.7Hz,1H),5.29(d,J=7.5,2.6Hz,1H).

[0162] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :330.1489.

[0163] Embodiment 10

[0164] A method for synthesizing 4,5-diphenyl-2-(3-methylphenyl)-4,5-dihydrooxazole comprises the following steps:

[0165] Step S1, in a 25 mL three-necked flask, magnetic particles, 0.5 mmol 1,2-diphenylethylene, 1.5 mmol m-methylbenzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide were sequentially added and mixed.

[0166] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0167] Step S3, performing addition reaction under the condition of power on.

[0168] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0169] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0170] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0171] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0172] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 4,5-diphenyl-2-(3-methylphenyl)-4,5-dihydrooxazole (140.8 mg) was obtained by separation, and the yield was 90%.

[0173] The structural formula of 4,5-diphenyl-2-(3-methylphenyl)-4,5-dihydrooxazole is:

[0174]

[0175] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.09–7.96(m,2H),7.48–7.41(m,7H),7.31–7.25(m,5H),5.49(d,J=7.6Hz,1H),5.29(d,J=7.8Hz,1H),2.49(s,3H).

[0176] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :314.1539.

[0177] Embodiment 11

[0178] A method for synthesizing 4,5-diphenyl-2-(3-methoxyphenyl)-4,5-dihydrooxazole comprises the following steps:

[0179] Step S1, in a 25 mL three-necked flask, magnetic particles, 0.5 mmol 1,2-diphenylethylene, 1.5 mmol m-methoxybenzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide were sequentially added and mixed.

[0180] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0181] Step S3, performing addition reaction under the condition of power on.

[0182] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0183] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0184] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0185] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0186] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 4,5-diphenyl-2-(3-methoxyphenyl)-4,5-dihydrooxazole 52.6 mg was obtained by separation, and the yield was 32%.

[0187] The structural formula of 4,5-diphenyl-2-(3-methoxyphenyl)-4,5-dihydrooxazole is:

[0188]

[0189] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ7.79–7.68(m,2H),7.47–7.32(m,7H),7.28–7.09(m,5H),5.46(d,J=7.6Hz,1H),5.26(d,J=7.6Hz,1H),3.90(s,3H).

[0190] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :330.1489.

[0191] Embodiment 12

[0192] A method for synthesizing 4,5-diphenyl-2-(4-fluorophenyl)-4,5-dihydrooxazole comprises the following steps:

[0193] Step S1, add a magnetic particle, 0.5 mmol 1,2-diphenylethylene, 1.5 mmol p-fluorobenzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide in sequence into a 25 mL three-necked flask and mix.

[0194] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0195] Step S3, performing addition reaction under the condition of power on.

[0196] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0197] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0198] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0199] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0200] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 4,5-diphenyl-2-(4-fluorophenyl)-4,5-dihydrooxazole (126.8 mg) was obtained by separation, and the yield was 80%.

[0201] The structural formula of 4,5-diphenyl-2-(4-fluorophenyl)-4,5-dihydrooxazole is:

[0202]

[0203] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.27–8.16(m,2H),7.49–7.36(m,7H),7.28–7.11(m,5H),5.48(d,J=7.7Hz,1H),5.29(d,J=7.5,2.6Hz,1H).

[0204] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :318.1289.

[0205] Embodiment 13

[0206] A method for synthesizing 4,5-diphenyl-2-(4-methylphenyl)-4,5-dihydrooxazole comprises the following steps:

[0207] Step S1, in a 25 mL three-necked flask, magnetic particles, 0.5 mmol 1,2-diphenylethylene, 1.5 mmol p-methylbenzamide, 0.5 mmol tetrabutylammonium hexafluorophosphate, and 0.05 mmol sodium iodide were added in sequence and mixed.

[0208] Step S2: After the mixing is completed, a carbon rod electrode is used as a positive electrode and a nickel sheet electrode is used as a negative electrode. The size of the negative electrode nickel sheet is 15 mm×15 mm×1 mm.

[0209] Step S3, performing addition reaction under the condition of power on.

[0210] Step S31, evacuate the system to a nitrogen atmosphere, then add 10 mL of 1,2-dichloroethane to make the organic solution cover the electrode.

[0211] Step S32, react for 4.5 hours at a current of 10 mA and a temperature of 80°C.

[0212] Step S4: after the addition reaction is completed, the remaining 1,2-dichloroethane is removed by distillation under reduced pressure.

[0213] Step S5, purifying the product obtained in step S4 by silica gel column chromatography with a standard particle size of 300 mesh.

[0214] The mixture of petroleum ether and ethyl acetate was used as the eluent for elution, and the volume ratio of petroleum ether to ethyl acetate added was 5:1. The target product 4,5-diphenyl-2-(4-methylphenyl)-4,5-dihydrooxazole (133.1 mg) was obtained by separation, and the yield was 85%.

[0215] The structural formula of 4,5-diphenyl-2-(4-methylphenyl)-4,5-dihydrooxazole is:

[0216]

[0217] The H NMR spectrum is: 1 H NMR (400 MHz, CDCl 3 )δ8.16–8.08(m,2H),7.49–7.24(m,12H),5.48(d,J=7.6Hz,1H),5.28(d,J=7.5Hz,1H),2.49(s,3H).

[0218] High resolution mass spectrometry test results: HRMS (ESI) [M + H] + :314.1539.

[0219] Therefore, the present invention adopts the above-mentioned method for synthesizing an oxazoline compound to provide a method for synthesizing an oxazoline compound by cyclization of olefins and amides with mild reaction conditions and convenient operation, and does not require the addition of an external oxidant and a base.

[0220] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solution of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solution to deviate from the spirit and scope of the technical solution of the present invention.

Claims

1. A method for synthesizing an oxazoline compound, characterized in that: The following steps are involved: Step S1, sequentially adding a magneton, an olefin compound, an amide compound, an electrolyte, and an iodine catalyst into a three-necked flask and mixing them; Step S2: After the mixing is completed, a carbon rod electrode is provided as a positive electrode and a nickel sheet electrode is provided as a negative electrode; Step S3, performing an addition reaction under the condition of power on; Step S31, pumping the system to a nitrogen atmosphere, then adding an organic solvent so that the organic solution covers the electrode; Step S32, reacting for 4-5 hours at a current of 8-12 mA and a temperature of 60-80° C.; Step S4, after the addition reaction is completed, the organic solvent is removed, and the obtained product is purified to obtain an oxazoline compound; Step S41, removing the remaining organic solvent by distillation under reduced pressure; Step S42: Purify the product obtained in step S41 by column chromatography and elute with a mixture of petroleum ether and ethyl acetate as an eluent to obtain an oxazoline compound.

2. A method for synthesizing an oxazoline compound according to claim 1, characterized in that: The olefin compound is a styrene compound, which is a styrene having electron-withdrawing or electron-donating substituents at the ortho-position, meta-position or para-position on the benzene ring.

3. A method for synthesizing an oxazoline compound according to claim 2, characterized in that: The olefin compound is specifically one of styrene substituted with halogen at positions 2, 3, and 4; styrene substituted with methyl at positions 2, 3, and 4; styrene substituted with methoxy at positions 2, 3, and 4; and styrene substituted with trifluoromethyl at positions 2, 3, and 4.

4. A method for synthesizing an oxazoline compound according to claim 1, characterized in that: The amide compound is a benzamide compound, which has an electron-withdrawing or electron-donating substituent at the ortho, meta, or para position on the benzene ring.

5. A method for synthesizing an oxazoline compound according to claim 4, characterized in that: The amide compound is specifically one of benzamide substituted with halogen at positions 2, 3, and 4; benzamide substituted with methyl at positions 2, 3, and 4; and benzamide substituted with methoxy at positions 2, 3, and 4.

6. A method for synthesizing an oxazoline compound according to claim 1, characterized in that: In step S1, the amount of the olefin compound used is 0.3-0.8 mmol; the amount of the amide compound used is 1-1.5 mmol.

7. A method for synthesizing an oxazoline compound according to claim 6, characterized in that: In step S1, the organic solvent is 1,2-dichloroethane, and the amount thereof is 8-12 mL; the electrolyte is tetrabutylammonium hexafluorophosphate, and the amount thereof is 0.3-1 mmol; and the iodine catalyst is sodium iodide, and the amount thereof is 0.03-0.10 mmol.

8. A method for synthesizing an oxazoline compound according to claim 1, characterized in that: In step S42, column chromatography is performed using silica gel with a standard particle size of 200-300 mesh for purification; the volume ratio of petroleum ether to ethyl acetate added is 1:1 to 10:1.

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