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Synthesis method of 3-aryl-4,5-dihydroisoxazole-5-yl-methyl sulfonate and analogs

A kind of technology of methyl methanesulfonate and dihydroisoxazole, applied in the synthesis field of isoxazole heterocycle

Active Publication Date: 2020-01-10
HUAIBEI NORMAL UNIVERSITY
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  • Application Information

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Problems solved by technology

[0004] However, the synthesis of isoxazolines by combining cheap metal iron with high-valent iodine has not been fully studied. Therefore, exploring the efficient construction of structurally diverse 3-phenyl-4,5-dihydroisoxazole-5 -Methanesulfonate and similar methods are still very necessary

Method used

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  • Synthesis method of 3-aryl-4,5-dihydroisoxazole-5-yl-methyl sulfonate and analogs
  • Synthesis method of 3-aryl-4,5-dihydroisoxazole-5-yl-methyl sulfonate and analogs
  • Synthesis method of 3-aryl-4,5-dihydroisoxazole-5-yl-methyl sulfonate and analogs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Optimization of reaction conditions

[0029] (E)-1-phenylbut-3-ene-1-oxime (1a, 32.2mg, 0.2mmol), iron catalyst (5mol%), organic solvent (1.0mL) and [hydroxyl (p-toluenesulfonyloxy ) iodo]benzene (2a, 98.1mg, 0.25mmol) was sequentially added into a 10mL reaction tube. The reaction tube was stirred at room temperature, and then the mixture in the reaction tube was detected by TLC. After the reaction was completed, distilled water (10 mL) was added and extracted with an organic solvent. The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product, which was purified by flash chromatography (silica gel, petroleum ether / ethyl acetate=3:1-9:1) to obtain product 3a.

[0030]

[0031]

[0032] In the screening process of reaction conditions, no catalyst was added (label 1), and the influence of different iron catalysts on the reaction (label 2-8), the influence of different reaction solvents on...

Embodiment 2

[0034] (E)-1-phenylbut-3-ene-1-oxime (1a, 32.2mg, 0.2mmol), Fe(acac) 2 (2.5 mg, 5 mol%), DCM (1.0 mL) and [hydroxy(p-toluenesulfonyloxy)iodo]benzene (2a, 98.1 mg, 0.25 mmol) were sequentially added to a 10 mL reaction tube. The reaction tube was stirred at room temperature for 6 h, and then the mixture in the reaction tube was detected by TLC. After the reaction was completed, distilled water (10 mL) was added, and extracted with dichloromethane (DCM, 3×10 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product, which was purified by flash chromatography (silica gel, petroleum ether / ethyl acetate=3:1~9:1) to obtain 53.7 mg of product 3a, white Solid, yield 81%.

[0035]

[0036] (3-Phenyl-4,5-dihydroisoxazol-5-yl)methyl 4-methylbenzenesulfonate(3a):White solid; 53.7mg, 81% yield; 1 H NMR (600MHz, CDCl 3)δ7.79(d, J=8.4Hz, 2H), 7.63–7.61(m, 2H), 7.44–7.38(m, 3H), 7.34(d, J=7.8Hz, 2H), 4....

Embodiment 3

[0038] According to the reaction conditions of Example 2, only the structure of the substrate 1 was changed to obtain the reaction product 3b-3s, and the specific results are as follows:

[0039]

[0040] (3-(p-Tolyl)-4,5-dihydroisoxazol-5-yl)methyl

[0041] 4-methylbenzenesulfonate (3b): White solid; 53.9mg, 78% yield; 1 H NMR (400MHz, CDCl 3 )δ7.79(d, J=8.4Hz, 2H), 7.50(d, J=8.0Hz, 2H), 7.34(d, J=8.0Hz, 2H), 7.20(d, J=8.0Hz, 2H) ,4.94–4.87(m,1H),4.16–4.08(m,2H),3.42(dd,J=17.2,10.8Hz,1H),3.21(dd,J=16.8,6.8Hz,1H),2.44(s ,3H),2.38(s,3H). 13 C NMR (101MHz, CDCl 3 )δ156.2, 145.2, 140.7, 132.5, 129.9, 129.4, 128.0, 126.7, 126.0, 77.2, 69.2, 37.4, 21.6, 21.4. HRMS (ESI) ([M+H] + )Calcd.For[C 18 h 20 NO 4 S] + :346.1108,Found:346.1108.

[0042]

[0043] (3-(4-Ethylphenyl)-4,5-dihydroisoxazol-5-yl)methyl

[0044] 4-methylbenzenesulfonate (3c): White solid; 53.9mg, 75% yield; 1 H NMR (400MHz, CDCl 3 )δ7.79(d, J=8.4Hz, 2H), 7.53(d, J=8.4Hz, 2H), 7.34(d, J=8.0Hz, 2H),...

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Abstract

The invention discloses a synthesis method of 3-aryl-4,5-dihydroisoxazole-5-ylmethyl p-toluenesulfonate and analogs, belonging to the technical field of organic chemistry. Iron (II) is used to catalyze Koser high iodine reagent (HIRS) to promote I-O bond cleavage and unsaturated oxime radical cyclization, thus obtaining 3-phenyl-4,5-dihydroisoxazole-5-yl sulfonate, an isoxazoline skeleton product.Sulfonate groups as leaving groups can be further converted into various series of analogs. The method provides a simple, cheap and efficient way to synthesize the 3-aryl-4,5-dihydroisoxazole-5-ylmethyl sulfonate series.

Description

technical field [0001] The present invention relates to the synthesis method of isoxazole heterocyclic ring, in particular to a synthesis method of 3-aryl-4,5-dihydroisoxazol-5-yl methylsulfonate and analogues, which belongs to the field of organic chemistry technology field. Background technique [0002] Isoxazoline compounds, especially 3-aryl-4,5-dihydroisoxazol-5-yl methylsulfonate and analogs, are widely used as chiral ligands in biological natural products, pesticides and Medicine, and asymmetric catalysis and other fields. In the past few years, a great deal of research has been done on the synthesis of isoxazolines, including transition metal-catalyzed and metal-free strategies. For oxime compounds containing inactive C═C, more attention has been paid to them due to their possibility of forming isoxazolines. However, most of the cyclization reactions are severely limited by the coordination ability of the hydroxyl group, the sensitivity to oxygen (air), and the la...

Claims

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Application Information

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IPC IPC(8): C07D261/04
CPCC07D261/04
Inventor 李洪基杨诗超
Owner HUAIBEI NORMAL UNIVERSITY
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