CN111100085A - Preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound - Google Patents
Preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound Download PDFInfo
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- CN111100085A CN111100085A CN201911414178.XA CN201911414178A CN111100085A CN 111100085 A CN111100085 A CN 111100085A CN 201911414178 A CN201911414178 A CN 201911414178A CN 111100085 A CN111100085 A CN 111100085A
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- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
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Abstract
The invention discloses a preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound, which comprises the steps of taking a deep eutectic solvent as a reaction solvent for a reaction substrate 2-aminophenol compound and a keto acid compound, magnetically stirring the reaction solvent under an oil bath pan, carrying out post-treatment after the reaction is finished to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound, uniformly mixing choline chloride and urea in a molar ratio of 1: 2, and then heating the mixture to a uniform and transparent liquid at 80 ℃ to form the deep eutectic solvent.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
Background
The 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is an organic heterocyclic compound with photophysical and photochemical activity, antibacterial activity and antitumor activity, and as the potential application of the compound in material and pharmaceutical chemistry becomes more and more important, the development of efficient and green methodology for obtaining benzoxazine derivatives is very attractive.
Currently, several methods for preparing benzoxazine compounds are as follows:
synthesizing 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one by taking 2-aminophenol and keto acid as reaction substrates;
the ring opening of benzoxazole is reacted with keto acid compound to synthesize 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one;
however, the catalysts adopted by the two methods have the defects of insufficient environmental protection and limited substrate range, so that the development of a green preparation method with wider application range has positive significance.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound, which has the advantages of simple operation process, mild reaction conditions, low cost, environmental protection and popularization and application value.
A process for the preparation of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound comprising:
taking a deep eutectic solvent as a reaction solvent for the reaction substrate 2-aminophenol compound and the ketonic acid compound, magnetically stirring under an oil bath pan, and carrying out post-treatment after the reaction is finished to obtain a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-ketone compound;
the deep eutectic solvent is prepared from choline chloride and urea in a molar ratio of 1: 2 and then heating to a uniform, transparent liquid at 80 ℃.
Further, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is as follows, and the structural formula of the 2-aminophenol compound is as follows:
wherein R is selected from H, an electron withdrawing group or an electron donating group.
Further, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is as follows:
wherein R is1Selected from H, electron withdrawing groups or electron donating groups.
Further, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is as described above, the electron-withdrawing group of the 2-aminophenol compound comprises halogen, and the electron-donating group comprises methyl.
Further, the method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound as described above, wherein the 2-aminophenol compound is any one of 2-aminophenol, 4-chloro-2-aminophenol and 5-methyl-2-aminophenol.
Furthermore, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound comprises the steps that the electron-withdrawing group of the keto acid compound comprises halogen, and the electron-donating group comprises methyl and methoxy.
Further, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is any one of 4-fluorobenzoylformic acid, 4-chlorobenzoylformic acid, 4-bromobenzoylformic acid, 2-bromobenzoylformic acid, 4-methylbenzoylformic acid, 4-methoxybenzoylformic acid and α -oxo-2-furanacetic acid.
Further, the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound is characterized in that the reaction is carried out in an oil bath kettle at the temperature of 80 ℃ by magnetic stirring, and the reaction time is not less than 0.5H.
Further, in the above-mentioned method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound, the molar ratio of the 2-aminophenol compound to the keto acid compound as a reaction substrate is 1: 2.
Further, the post-treatment of the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound comprises purification and drying, wherein the purification adopts column chromatography separation, and the drying adopts vacuum drying, and the drying temperature is 30 ℃.
The preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-ketone compound solves the problem that the catalyst used in the existing reaction is not environment-friendly, and has the following advantages:
(1) the preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound provided by the invention adopts a deep eutectic solvent as a reaction solvent, does not need other organic solvents or any other catalysts, is green and environment-friendly, and has the advantages of cheap and easily-obtained reaction solvent synthesis method and low cost, thereby being a novel method for synthesizing the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
(2) The preparation method of the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound provided by the invention is green and efficient, few in byproducts, easy to separate the target product, green and environment-friendly in the whole process, and compared with the traditional chemical catalysis method, the yield of the target product synthesized in a deep eutectic solvent is higher, and the reaction conditions are more environment-friendly.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention are described clearly and completely below, and it is obvious that the described embodiments are some, not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A preparation method of 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound comprises the following synthetic route:
the method specifically comprises the following steps:
(1) taking a 10mL reaction bottle, adding 0.2mmol of 2-aminophenol, 0.4mmol of benzoylformic acid and 2mL of deep eutectic solvent (the molar ratio of choline chloride to urea is 1: 2);
(2) placing the reaction bottle in the step (1) under an oil bath pan at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) and (3) carrying out column chromatography separation on the crude product obtained in the step (2), wherein the eluent is a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1: 6, and drying at 30 ℃ for 3H to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
And (3) performing nuclear magnetic resonance hydrogen spectrum determination on the prepared target product:
1H NMR(500MHz,DMSO)δ8.19(d,J＝6.9Hz,2H),7.84(d,J＝6.8Hz,1H),7.63–7.50(m,4H),7.44(dd,J＝11.5,4.5Hz,2H).13C NMR(126MHz,DMSO):δ152.54,151.82,146.82,134.85,131.78,131.54,131.45,129.77,129.35,128.55,125.85,116.52。
example 2
A preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
(1) taking a 10mL reaction bottle, adding 0.2mmol of 4-chloro-2-aminophenol, 0.4mmol of benzoylformic acid and 2mL of deep eutectic solvent (the molar ratio of choline chloride to urea is 1: 2);
(2) placing the reaction bottle in the step (1) under an oil bath pan at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) and (3) carrying out column chromatography separation on the crude product obtained in the step (2), wherein the eluent is a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1: 6, and drying at 30 ℃ for 3H to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
And (3) performing nuclear magnetic resonance hydrogen spectrum determination on the prepared target product:
1H NMR(500MHz,DMSO)δ8.19(d,J＝7.2Hz,2H),7.91(d,J＝2.4Hz,1H),7.64(dd,J＝8.8,2.4Hz,1H),7.61–7.47(m,4H)。13C NMR(126MHz,CDCl3)δ151.94,151.84,145.18,133.87,132.31,132.04,131.13,130.84,129.75,129.00,128.62,117.43.
example 3
A preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
(1) taking a 10mL reaction bottle, adding 0.2mmol of 5-methyl-2-aminophenol, 0.4mmol of benzoylformic acid and 2mL of deep eutectic solvent (the molar ratio of choline chloride to urea is 1: 2);
(2) placing the reaction bottle in the step (1) under an oil bath pan at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) and (3) carrying out column chromatography separation on the crude product obtained in the step (2), wherein the eluent is a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1: 6, and drying at 30 ℃ for 3H to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
And (3) performing nuclear magnetic resonance hydrogen spectrum and carbon spectrum determination on the prepared target product:
1H NMR(500MHz,CDCl3)δ8.31(d,J＝2.9Hz,2H),7.71(d,J＝8.1Hz,1H),7.49(dd,J＝12.8,5.3Hz,3H),7.19(d,J＝8.1Hz,1H),7.12(s,1H),2.48(s,3H)。13C NMR(126MHz,CDCl3)δ152.58,149.67,146.48,142.65,134.40,131.25,129.81,129.42,129.12,128.44,126.82,116.32,21.87.
example 4
A preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
(1) taking a 10mL reaction bottle, adding 0.2mmol of 2-aminophenol, 0.4mmol of 4-chlorobenzoyl formic acid and 2mL of deep eutectic solvent (the mol ratio of choline chloride to urea is 1: 2);
(2) placing the reaction bottle in the step (1) under an oil bath pan at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) and (3) carrying out column chromatography separation on the crude product obtained in the step (2), wherein the eluent is a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1: 6, and drying at 30 ℃ for 3H to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
And (3) performing nuclear magnetic resonance hydrogen spectrum and carbon spectrum determination on the prepared target product:
1H NMR(500MHz,CDCl3)δ8.34(d,J＝8.7Hz,2H),7.84(d,J＝9.4Hz,1H),7.53(t,J＝7.8Hz,1H),7.46(d,J＝8.7Hz,2H),7.40(t,J＝8.3Hz,1H),7.34(d,J＝8.2Hz,1H).13CNMR(126MHz,CDCl3):δ152.30,149.60,146.59,137.99,132.61,131.67,131.54,130.96,129.61,128.80,125.84,116.35。
example 5
A preparation method of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
(1) taking a 10mL reaction bottle, adding 0.2mmol of 2-aminophenol, 0.4mmol of 4-methylbenzoyl formic acid and 2mL of deep eutectic solvent (the molar ratio of choline chloride to urea is 1: 2);
(2) placing the reaction bottle in the step (1) under an oil bath pan at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) and (3) carrying out column chromatography separation on the crude product obtained in the step (2), wherein the eluent is a mixed solution of ethyl acetate and petroleum ether with the volume ratio of 1: 6, and drying at 30 ℃ for 3H to obtain the 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-one compound.
And (3) performing nuclear magnetic resonance hydrogen spectrum and carbon spectrum determination on the prepared target product:
1H NMR(500MHz,CDCl3)δ8.26(d,J＝8.3Hz,2H),7.84(d,J＝9.3Hz,1H),7.50(t,J＝8.5Hz,1H),7.38(t,J＝7.7Hz,1H),7.32(t,J＝9.3Hz,3H),2.46(s,3H).13C NMR(126MHz,CDCl3):δ152.52,150.85,146.56,142.19,131.87,131.60,130.96,129.59,129.45,129.30,125.65,116.27,21.73。
as can be seen from Table 1, the effect of the reaction substrate on the yield of 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound synthesized by the present invention is best seen in that the reaction substrate has the best effect on the production of benzoylformic acid having an electron-withdrawing group, such as fluorine, chlorine and bromine, with the highest and substantially constant yield and the electron-donating group has the lowest yield of p-methoxy group, and Table 1 shows that the different substrates have the lowest yields for the synthesis of 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A process for preparing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound comprising:
taking a deep eutectic solvent as a reaction solvent for the reaction substrate 2-aminophenol compound and the ketonic acid compound, magnetically stirring under an oil bath pan, and carrying out post-treatment after the reaction is finished to obtain a 3-aryl-2H-benzo [ β ] [1,4] benzoxazine-2-ketone compound;
the deep eutectic solvent is prepared from choline chloride and urea in a molar ratio of 1: 2 and then heating to a uniform, transparent liquid at 80 ℃.
2. The process for preparing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the 2-aminophenol compound has the formula:
wherein R is selected from H, an electron withdrawing group or an electron donating group.
3. The method of preparing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the ketoacid compound has the structural formula:
wherein R is1Selected from H, electron withdrawing groups or electron donating groups.
4. The method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 2, wherein the electron-withdrawing group of the 2-aminophenol compound comprises a halogen and the electron-donating group comprises a methyl group.
5. The method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 4, wherein the 2-aminophenol compound is any one of 2-aminophenol, 4-chloro-2-aminophenol and 5-methyl-2-aminophenol.
6. The method of claim 3, wherein said keto acid compound comprises a halogen and said electron-donating group comprises a methyl group or a methoxy group.
7. The method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 6, wherein the keto acid compound is any one of 4-fluorobenzoylformic acid, 4-chlorobenzoylformic acid, 4-bromobenzoylformic acid, 2-bromobenzoylformic acid, 4-methylbenzoylformic acid, 4-methoxybenzoylformic acid, and α -oxo-2-furanacetic acid.
8. The process for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the reaction is carried out by magnetic stirring in an oil bath at 80 ℃ for a reaction time of not less than 0.5 hour.
9. The method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the molar ratio of the 2-aminophenol compound to the keto acid compound as the reaction substrate is 1: 2.
10. The process for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the post-treatment comprises purification by column chromatography and drying by vacuum drying at 30 ℃.
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| CN111943924A (en) * | 2020-07-31 | 2020-11-17 | 吉林警察学院 | Synthesis method of chromanone compounds |
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| CN111943924A (en) * | 2020-07-31 | 2020-11-17 | 吉林警察学院 | Synthesis method of chromanone compounds |
| CN111943924B (en) * | 2020-07-31 | 2023-03-28 | 吉林警察学院 | Synthesis method of chromanone compounds |
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