CN111100085B - Preparation method of 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound - Google Patents
Preparation method of 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound Download PDFInfo
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- CN111100085B CN111100085B CN201911414178.XA CN201911414178A CN111100085B CN 111100085 B CN111100085 B CN 111100085B CN 201911414178 A CN201911414178 A CN 201911414178A CN 111100085 B CN111100085 B CN 111100085B
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Abstract
The invention discloses a preparation method of a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound, which comprises the following steps: magnetically stirring a reaction substrate 2-aminophenol compound and a keto acid compound in an oil bath by taking a deep co-melting solvent as a reaction solvent, and performing post-treatment after the reaction is finished to obtain a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound; the deep co-melting solvent is choline chloride and urea in a molar ratio of 1:2, and then heating to 80 ℃ to obtain the uniform and transparent liquid. The method disclosed by the invention is simple in operation process, mild in reaction condition, low in cost, environment-friendly and has popularization and application values.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method of a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound.
Background
The 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-ketone compound is an organic heterocyclic compound with photophysical and photochemical activity, antibacterial activity and antitumor activity. As its potential use in materials and pharmaceutical chemistry becomes increasingly important, it is very attractive to develop efficient and green methodologies for obtaining benzoxazine derivatives.
At present, the preparation method of the benzoxazine compound comprises the following synthetic methods:
synthesizing 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one by taking 2-aminophenol and keto acid as reaction substrates;
synthesizing 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one through the reaction of benzoxazole ring opening and keto acid compounds;
however, the catalysts adopted by the two methods have the defect of insufficient environmental protection, and the substrate range is limited, so that the development of the 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 the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound, which has the advantages of simple operation process, mild reaction condition, 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:
magnetically stirring a reaction substrate 2-aminophenol compound and a keto acid compound in an oil bath by taking a deep co-melting solvent as a reaction solvent, and performing post-treatment after the reaction is finished to obtain a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound;
the deep eutectic solvent is prepared from choline chloride and urea in a molar ratio of 1:2, and then heating to 80 ℃ to obtain the uniform and transparent liquid.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-ketone compound comprises the following steps of:
wherein R is selected from H, electron withdrawing group or electron donating group.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-ketone compound comprises the following steps:
wherein R is 1 Selected from H, electron withdrawing group or electron donating group.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound comprises the following steps of: halogen; the electron donating group includes: methyl group.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-ketone compound comprises the following steps: any one of 2-aminophenol, 4-chloro-2-aminophenol and 5-methyl-2-aminophenol.
Further, a method for producing the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound as described above, wherein the keto acid compound electron withdrawing group comprises: halogen; the electron donating group includes: methyl, methoxy.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound comprises the following steps: 4-fluorobenzoic acid, 4-chlorobenzoic acid, 4-bromobenzoic acid, 2-bromobenzoic acid, 4-methylbenzoic acid, 4-methoxybenzoic acid, and alpha-oxo-2-furanacetic acid.
Further, the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound comprises the steps of magnetically stirring the reaction in an oil bath at 80 ℃; the reaction time is not less than 0.5h.
Further, according to the preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound, the molar ratio of the reaction substrate 2-aminophenol compound to the keto acid compound is 1:2.
further, a process for preparing a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound as described above, said post-treatment comprising: purifying and drying; the purification adopts column chromatography separation; the drying was carried out in vacuo at a drying temperature of 30 ℃.
The preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one 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 [ beta ] [1,4] benzoxazine-2-one compound provided by the invention adopts the deep eutectic solvent as the reaction solvent, does not need other organic solvents or any other catalysts, is environment-friendly, and has the advantages of low cost, easy obtainment and low cost. Is a novel method for synthesizing 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compounds.
(2) The preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound provided by the invention is green and efficient, few in byproducts, easy to separate target products, green and environment-friendly in the whole process, and compared with the traditional chemical catalysis method, the method has the advantages that the yield of the target products is higher in the deep eutectic solvent, and the reaction condition is more environment-friendly.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions in the present invention will be clearly and completely described below, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
A preparation method of a 3-aryl-2H-benzo [ beta ] [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 benzoyl 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) into an oil bath pot at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) Performing column chromatography separation on the crude product obtained in the step (2), wherein the eluent adopts a mixed solution of ethyl acetate and petroleum ether, and the volume ratio is 1:6, drying at 30℃for 3 hours to give a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound.
And (3) measuring nuclear magnetic resonance hydrogen spectrum of the prepared target product:
1 H 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). 13 C 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
The preparation method of the 3-aryl-2H-benzo [ beta ] [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 benzoic 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) into an oil bath pot at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) Performing column chromatography separation on the crude product obtained in the step (2), wherein the eluent adopts a mixed solution of ethyl acetate and petroleum ether, and the volume ratio is 1:6, drying at 30℃for 3 hours to give a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound.
And (3) measuring nuclear magnetic resonance hydrogen spectrum of the prepared target product:
1 H 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)。 13 C NMR(126MHz,CDCl 3 )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
The preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
((1) taking a 10mL reaction bottle, and adding 0.2mmol of 5-methyl-2-aminophenol, 0.4mmol of benzoyl 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) into an oil bath pot at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) Performing column chromatography separation on the crude product obtained in the step (2), wherein the eluent adopts a mixed solution of ethyl acetate and petroleum ether, and the volume ratio is 1:6, drying at 30℃for 3 hours to give a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound.
And (3) measuring nuclear magnetic resonance hydrogen spectrum and carbon spectrum of the prepared target product:
1 H 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)。 13 C NMR(126MHz,CDCl 3 )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
The preparation method of the 3-aryl-2H-benzo [ beta ] [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 co-melting solvent (the molar ratio of choline chloride to urea is 1:2);
(2) Placing the reaction bottle in the step (1) into an oil bath pot at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) Performing column chromatography separation on the crude product obtained in the step (2), wherein the eluent adopts a mixed solution of ethyl acetate and petroleum ether, and the volume ratio is 1:6, drying at 30℃for 3 hours to give a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound.
And (3) measuring nuclear magnetic resonance hydrogen spectrum and carbon spectrum of the prepared target product:
1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 ):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
The preparation method of the 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound specifically comprises the following steps:
((1) taking a 10mL reaction bottle, and 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) into an oil bath pot at 80 ℃ for magnetic stirring, and reacting for 2 hours to obtain a crude product;
(3) Performing column chromatography separation on the crude product obtained in the step (2), wherein the eluent adopts a mixed solution of ethyl acetate and petroleum ether, and the volume ratio is 1:6, drying at 30℃for 3 hours to give a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound.
And (3) measuring nuclear magnetic resonance hydrogen spectrum and carbon spectrum of the prepared target product:
1 H NMR(500MHz,CDCl 3 )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). 13 C NMR(126MHz,CDCl 3 ):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 the synthetic 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one compound of the present invention is best, among the reactants, of benzoic acid having an electron withdrawing group such as: the yields of fluorine, chlorine and bromine are the highest and essentially unchanged, while the yields of p-methoxy groups donating electron groups are the lowest. TABLE 1 Synthesis of 3-aryl-2H-benzo [ beta ] [1,4] benzoxazin-2-one Compounds from different substrates
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the 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 scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (4)
1. A process for the preparation of a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound, comprising:
magnetically stirring a reaction substrate 2-aminophenol compound and a keto acid compound in an oil bath by taking a deep co-melting solvent as a reaction solvent, and performing post-treatment after the reaction is finished to obtain a 3-aryl-2H-benzo [ beta ] [1,4] benzoxazine-2-one compound;
the deep eutectic solvent is prepared from choline chloride and urea in a molar ratio of 1:2, uniformly mixing, and heating to uniform and transparent liquid at 80 ℃ to form the composite material;
the 2-aminophenol compound is as follows: any one of 2-aminophenol, 4-chloro-2-aminophenol, 5-methyl-2-aminophenol;
the keto acid compound is as follows: 4-fluorobenzoic acid, 4-chlorobenzoic acid, 4-bromobenzoic acid, 2-bromobenzoic acid, 4-methylbenzoic acid, 4-methoxybenzoic acid, and alpha-oxo-2-furanacetic acid.
2. The process for the preparation of 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, characterized in that the reaction is magnetically stirred in an oil bath at 80 ℃; the reaction time is not less than 0.5h.
3. 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 reaction substrate 2-aminophenol compound to the keto acid compound is 1:2.
4. the method for producing a 3-aryl-2H-benzo [ β ] [1,4] benzoxazin-2-one compound according to claim 1, wherein the post-treatment comprises: purifying and drying; the purification adopts column chromatography separation; the drying was carried out in vacuo at a drying temperature of 30 ℃.
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| 深共熔溶剂中β-二羰基化合物的α-酰基化;冯柏成等;《精细化工》;20190809(第01期);全文 * |
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