Preparation method for 4-aryl-6-methoxycarbonyl benzoxazine compound

A technology of methoxycarbonylbenzene and compounds, which is applied in the field of preparation of 4-aryl-6-methoxycarbonylbenzoxazine compounds, and can solve the problems such as many synthesis steps, long reaction time and poor selectivity of o-aminophenol , to achieve the effect of short reaction time, high yield and easy operation

Active Publication Date: 2015-06-10
GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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Problems solved by technology

[0004] At present, the synthetic method of the reported benzoxazine compound mainly contains following several kinds: (1) nucleophilic substitution reaction (Tetrahedron Lett.,2006,47(44):7823 –7826), however, the application of this type of synthetic method is limited due to the numerous synthetic steps and poor selectivity of o-aminophenol
(2) Cyclization reaction between o-halogenated phenol and condensing agent (J.Org.Chem., 75(24):8533-8541), cyclization reaction between o-halogenated aniline and condensing agent (Tetrahedron Lett., 2009,50(27):3790–3793), but these two methods are catalyzed by heavy metals and require a long reaction time
(3) cyclization reaction (Bioorg.Med.Chem.Lett., 2006,16(11):2862-2867) between o-nitrophenol and cyclization reagent after nitro reduction, but this kind of method step is relatively More, lower total yield
At present, there is no report on the preparation of benzoxazine compounds from non-aromatic compounds.

Method used

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  • Preparation method for 4-aryl-6-methoxycarbonyl benzoxazine compound
  • Preparation method for 4-aryl-6-methoxycarbonyl benzoxazine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1: Preparation of 4-phenyl-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine

[0020] Methyl 3-dehydroshikimate (0.37g, 2.0mmol), aniline (0.19g, 2.0mmol), 1,2-dichloroethane (1ml), p-toluenesulfonic acid (0.02g, 0.10mmol), Dimethylsulfoxide (5ml) was added to the microwave reaction vial. The above system was reacted in a microwave reactor at 120°C (160W) for 5min, followed by TLC. After the aniline reaction was complete, cesium carbonate (1.95g, 6mmol) was added to the above system, and reacted at 180°C (800W) for 5min, TLC Follow up until the response is complete. After cooling the reaction solution, pour it into a beaker filled with 20ml of saturated saline, stir, and extract the product with ethyl acetate (3×20ml), combine the organic layers, dry, remove the solvent by rotary evaporation, column separation, ethyl acetate-petroleum Eluted with ether, crystallized to obtain 0.48 g of white solid 4-phenyl-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine, yield...

Embodiment 2

[0021] Example 2: Preparation of 4-(4-methoxyphenyl)-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine

[0022] Methyl 3-dehydroshikimate (0.41g, 2.2mmol), 4-methoxyaniline (0.25g, 2.0mmol), formic acid (3.74μl, 0.10mmol), 1,2-dichloroethane (0.5 ml), dimethylsulfoxide (5ml) were added to the reaction flask. The above system was reacted in a microwave reactor at 130°C (240W) for 5min, followed by TLC. After the reaction of p-methoxyaniline was complete, cesium carbonate (1.95g, 6mmol) was added, and reacted at 180°C (800W) for 5min, TLC Follow up, after the response is complete. After cooling the reaction solution, pour it into a beaker filled with 20ml of saturated saline, stir, and extract the product with ethyl acetate (3×20ml), combine the organic layers, dry, remove the solvent by rotary evaporation, column separation, ethyl acetate-petroleum Eluted with ether, crystallized to give light yellow crystal 4-(4-methoxyphenyl)-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine ...

Embodiment 3

[0023] Example 3: Preparation of 4-(4-methylphenyl)-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine

[0024]Methyl 3-dehydroshikimate (0.46g, 2.4mmol), p-toluidine (0.21g, 2.0mmol), 1,2-dichloroethane (1ml), acetic acid (5.72μl, 0.10mmol), di Methyl sulfoxide (1.5ml) was added to the reaction flask, and the above system was reacted in a microwave reactor at 130°C (240W) for 5min, followed by TLC. After the reaction of p-toluidine was complete, cesium carbonate (1.95g, 6mmol) was added, React at 180°C (640W) for 5 minutes, followed by TLC, after the reaction is complete. After cooling the reaction solution, pour it into a beaker filled with 20ml of saturated saline, stir, and extract the product with ethyl acetate (3×20ml), combine the organic layers, dry, remove the solvent by rotary evaporation, column separation, ethyl acetate-petroleum Eluted with ether, crystallized to give 0.51 g of white solid 4-(4-methylphenyl)-6-methoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine, yield: ...

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Abstract

The invention discloses a preparation method for a 4-aryl-6-methoxycarbonyl benzoxazine compound. The 4-aryl-6-methoxycarbonyl benzoxazine compound is obtained by the steps of adding 3-methyl dehydroshikimate, anaromatic primary amine compound, 1,2-dichloroethane and a reaction solvent in a reaction flask at one time; carrying out a condensation-aromatization reaction in a microwave reactor under the effect of a protonic acid catalyst; then adding an acid-binding agent to further carry out a cyclization reaction. The raw material of 3-methyl dehydroshikimate is a non-aromatic compound that can be prepared by a simple method from a reproducible biomass resource; and can be obtained without depending on a fossil fuel, so that sustainable development and utilization can be achieved. Besides, a one-pot and microwave-assisted method is employed, so that operations is simple; reaction time is short; yield is high; and the reaction process is clean and environment-friendly and low in energy consumption.

Description

technical field [0001] The invention relates to the field of chemical industry, in particular to a preparation method of 4-aryl-6-methoxycarbonylbenzoxazine compounds. Background technique [0002] As Privileged scaffolds, benzoxazine structures widely exist in pesticides, pharmaceutical products, and biologically active molecules. For example: Benoxacor (Benoxacor) (Journal of Pesticides, 1999, 1 (2): 1-8) is a herbicide safener developed by Ciba-Geigy company, also known as an antidote, used to protect crops from herbicides In addition, oxazone is also an effective safener of the chloroacetamide herbicide dimethenamid. Levofloxacin (Levofloxacin) (Chinese Journal of Pharmaceutical Sciences, 2001, 36(12): 834-837) was launched in Japan in 1993 and has good curative effects on the treatment of respiratory tract infections, genitourinary system infections and skin and soft tissue infections, among which acute and chronic The effective rate and bacterial clearance rate of lo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D265/36
Inventor 邹永张恩生徐田龙魏文黄琦黄桐堃吕泽良
Owner GUANGZHOU CHEM CO LTD CHINESE ACADEMY OF SCI
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