CN110590679A - Method for catalytic synthesis of 5-substituted barbituric acid derivative by rare earth chloride - Google Patents
Method for catalytic synthesis of 5-substituted barbituric acid derivative by rare earth chloride Download PDFInfo
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- CN110590679A CN110590679A CN201910919814.8A CN201910919814A CN110590679A CN 110590679 A CN110590679 A CN 110590679A CN 201910919814 A CN201910919814 A CN 201910919814A CN 110590679 A CN110590679 A CN 110590679A
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- barbituric acid
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
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Abstract
The invention belongs to the technical field of synthetic chemistry, and particularly relates to a method for catalytic synthesis of a 5-substituted barbituric acid derivative by using rare earth chloride. In the invention, under the condition of taking rare earth chloride as a catalyst, halohydrocarbon and 1, 3-dimethyl barbituric acid are dissolved in an organic solvent, react for 6-10h at room temperature, and are separated and purified to obtain the 5-substituted barbituric acid derivative. The invention has simple and green synthesis process, excellent selectivity, higher yield and wide substrate range, and has wide application value in the fields of biology, pharmaceutical chemistry industry and the like.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a method for synthesizing a 5-substituted barbituric acid derivative under the catalysis of rare earth chloride.
Background
The barbituric acid derivatives are nitrogen heterocyclic skeleton compounds, generally have stronger physiological activity and important application in the fields of biology, medicine and chemical industry, wherein the barbituric acid derivatives substituted at the 5-position have potential functions of sedation, hypnosis, immunoregulation, tumor resistance and the like.
The traditional synthesis method of the compounds is realized by condensation reaction of malonate derivatives and urea under the action of strong alkali sodium alkoxide, but the reaction conditions are harsh, conditions such as inert gas protection, high temperature, anhydrous solvent and the like are usually required, side reactions are more, the yield is not high, and the product is difficult to separate; yet another approach is noble metal catalyzed reaction of aromatic hydrocarbons with diazo compounds reported by Lam, but this reaction uses noble metal catalysts, which is costly, and the diazo compounds are not stable enough, which has certain limitations.
Therefore, the problem to be solved by those skilled in the art is how to provide a simple and efficient method for synthesizing 5-substituted barbituric acid derivatives under mild reaction conditions.
Disclosure of Invention
In view of the above, the invention provides a method for catalytic synthesis of 5-substituted barbituric acid derivatives by rare earth chlorides, the synthesis process of the invention is simple and green, the invention has excellent selectivity and high yield, and the invention has wide substrate range, and the invention has wide application value in the fields of biology, pharmaceutical chemistry industry and the like.
A method for synthesizing 5-substituted barbituric acid derivatives by catalysis of rare earth chlorides comprises the following steps:
under the condition of taking rare earth chloride as a catalyst, dissolving halohydrocarbon and 1, 3-dimethyl barbituric acid in an organic solvent, reacting for 6-10 hours at room temperature, separating and purifying to obtain the 5-substituted barbituric acid derivative.
The beneficial effects of the above technical scheme are: the chemical reaction of the invention is carried out at room temperature, the conditions are simple, the operation is convenient, and if the temperature is too low, the yield of the product is reduced.
Preferably, in the above method for catalytic synthesis of 5-substituted barbituric acid derivatives using rare earth chlorides, the molar ratio of rare earth chlorides to halogenated hydrocarbon to 1, 3-dimethylbarbituric acid is (0.02-0.05): (1.0-1.20): 1.0.
the beneficial effects of the above technical scheme are: the efficiency is highest under the condition of the molar ratio, and the waste of raw materials is not caused.
Preferably, in the method for catalytically synthesizing the 5-substituted barbituric acid derivative by using the rare earth chloride, the separation and purification adopts a column chromatography separation method, and the eluting agent is dichloromethane and petroleum ether in a volume ratio of 1: 3.
Preferably, in the above method for the catalytic synthesis of 5-substituted barbituric acid derivatives using rare earth chlorides,the rare earth chlorides include but are not limited to yttrium trichloride YCl3YbCl, YbCl3Or samarium trichloride SmCl3。
The beneficial effects of the above technical scheme are: the rare earth chloride in the invention can effectively catalyze the reaction as the catalyst, shorten the reaction time and improve the product yield.
Preferably, in the above method for the catalytic synthesis of 5-substituted barbituric acid derivatives by using rare earth chlorides, the halogenated hydrocarbon includes, but is not limited to, methyl iodide, bromoethane, bromobenzene, 4-methylbromobenzene, 4-methoxyiodobenzene, 4-chloroiodobenzene or 2, 4-dimethyliodobenzene.
Preferably, in the above method for the catalytic synthesis of 5-substituted barbituric acid derivatives using rare earth chlorides, the organic solvent includes, but is not limited to, methanol, ethanol, or tetrahydrofuran.
The beneficial effects of the above technical scheme are: the organic solvent is used for fully dissolving each substrate, so that the reaction is easier to carry out.
According to the technical scheme, compared with the prior art, the invention discloses a method for synthesizing the 5-substituted barbituric acid derivative by catalyzing the rare earth chloride, which has the following advantages:
(1) the synthetic method is simple and green, and cheap and easily-obtained raw materials of halogenated hydrocarbon and 1, 3-dimethyl barbituric acid are used;
(2) the reaction condition of the invention is mild, and the corresponding product with high yield can be obtained by reaction at room temperature;
(3) the invention uses cheap and easily obtained rare earth chloride with stable property as a catalyst;
(4) the invention has good substrate universality, thereby being better convenient for application.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. 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:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.0mmol of methyl iodide and yttrium trichloride YCl as catalyst are added into a reaction tube in sequence30.05mmol, adding 2mL of solvent methanol, reacting at room temperature for 8 hours, concentrating the reaction solution after the reaction is finished, and performing column chromatography separation to obtain a corresponding product, wherein the separation yield is 87%.1H NMR(400MHz，CDCl3) δ:4.78-4.72(m, 1H), 3.40(s, 6H), 1.05(d, J ═ 6.2Hz, 3H). HRMS theoretical value C7H11N2O3(M+H)+: 171.0770, actual measured value: 171.0775.
example 2:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.2mmol of bromoethane and YbCl serving as a catalyst are sequentially added into a reaction tube30.02mmol, adding 2mL of solvent methanol, reacting at room temperature for 6 hours, concentrating the reaction solution after the reaction is finished, and performing column chromatography separation to obtain a corresponding product, wherein the separation yield is 85%.1H NMR(400MHz，CDCl3) δ:4.75(t, J ═ 5.8Hz, 1H), 3.42(s, 6H), 1.09-1.05(m, 2H), 0.95(t, J ═ 6.0Hz, 3H). HRMS theoretical value C8H13N2O3(M+H)+: 185.0926, actual measured value: 185.0930.
example 3:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.2mmol of bromobenzene and YbCl serving as a catalyst are sequentially added into a reaction tube30.05mmol, then adding 2mL of solvent ethanol, and reacting for 10 hours at room temperatureIn the method, after the reaction is finished, the reaction solution is concentrated, and the corresponding product is obtained through column chromatography separation, wherein the separation yield is 90%.1H NMR(400MHz，CDCl3) δ:7.41-7.34(m, 3H), 7.23(dd, J ═ 7.4, 1.8Hz, 2H), 4.67(s, 1H), 3.36(s, 6H). HRMS theoretical value C12H13N2O3(M+H)+: 233.0926, actual measured value: 233.0922.
example 4:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.2mmol of 4-methyl bromobenzene and samarium trichloride SmCl serving as a catalyst are sequentially added into a reaction tube30.05mmol, then adding 2mL of tetrahydrofuran solvent, reacting for 10 hours at room temperature, concentrating the reaction solution after the reaction is finished, and carrying out column chromatography separation to obtain a corresponding product, wherein the separation yield is 92%.1H NMR(400MHz，CDCl3) Delta 7.15(s, 4H), 4.93(s, 1H), 3.16(s, 6H), 2.29(s, 3H). HRMS theoretical value C13H15N2O3(M+H)+: 247.1083, actual measured value: 247.1085.
example 5:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.2mmol of 4-methoxy iodobenzene and a catalyst of samarium trichloride SmCl are sequentially added into a reaction tube30.04mmol, adding 2mL of solvent methanol, reacting at room temperature for 10 hours, concentrating the reaction solution after the reaction is finished, and performing column chromatography separation to obtain a corresponding product, wherein the separation yield is 95%.1H NMR(400MHz，CDCl3) δ 7.14(d, J ═ 8.8Hz, 2H), 6.89(d, J ═ 8.8Hz, 2H), 4.61(s, 1H), 3.79(s, 3H), 3.35(s, 6H). HRMS theoretical value C13H15N2O4(M+H)+: 263.1026, actual measured value: 263.1023.
example 6:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.1mmol of 4-chloroiodobenzene and yttrium trichloride YCl as catalyst are added into a reaction tube in sequence30.05mmol, adding 2mL of solvent methanol, reacting at room temperature for 8 hours, concentrating the reaction solution after the reaction is finished, and performing column chromatography separation to obtain a corresponding product, wherein the separation yield is 92%.1H NMR(400MHz，CDCl3) Delta 7.39-7.35 (m, 2H), 7.19-7.15 (m, 2H), 4.66(s, 1H), 3.37(d, 6H). HRMS theoretical value C12H12ClN2O3(M+H)+: 267.0531, actual measured value: 267.0528.
example 7:
1.0mmol of 1, 3-dimethyl barbituric acid, 1.2mmol of 2, 4-dimethyl iodobenzene and yttrium trichloride YCl as catalyst are added into a reaction tube in sequence30.03mmol, adding 2mL of solvent methanol, reacting at room temperature for 10 hours, concentrating the reaction solution after the reaction is finished, and performing column chromatography separation to obtain a corresponding product, wherein the separation yield is 90%.1H NMR(400MHz，CDCl3) δ 7.07(s, 1H), 7.00(d, J ═ 7.8Hz, 1H), 6.87(d, J ═ 7.8Hz, 1H), 4.82(s, 1H), 3.36(s, 6H), 2.35(s, 3H), 2.31(s, 3H). HRMS theoretical value C14H17N2O3(M+H)+: 261.1234, actual measured value: 261.1240.
the embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The device disclosed by the embodiment corresponds to the method disclosed by the embodiment, so that the description is simple, and the relevant points can be referred to the method part for description.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (6)
1. A method for synthesizing 5-substituted barbituric acid derivatives by catalysis of rare earth chlorides is characterized by comprising the following steps:
under the condition of taking rare earth chloride as a catalyst, dissolving halohydrocarbon and 1, 3-dimethyl barbituric acid in an organic solvent, reacting for 6-10 hours at room temperature, separating and purifying to obtain the 5-substituted barbituric acid derivative.
2. The method for catalytic synthesis of 5-substituted barbituric acid derivatives by using rare earth chlorides as claimed in claim 1, wherein the molar ratio of the rare earth chlorides to the halogenated hydrocarbon to the 1, 3-dimethyl barbituric acid is (0.02-0.05): (1.0-1.20): 1.0.
3. the method for catalytic synthesis of 5-substituted barbituric acid derivatives from rare earth chlorides as claimed in claim 1, wherein the separation and purification employs a column chromatography separation method, and the eluent is dichloromethane and petroleum ether at a volume ratio of 1: 3.
4. The method for catalytic synthesis of 5-substituted barbituric acid derivatives from rare earth chlorides as claimed in claim 1, wherein said rare earth chlorides include but are not limited to yttrium trichloride YCl3YbCl, YbCl3Or samarium trichloride SmCl3。
5. The method for catalytic synthesis of 5-substituted barbituric acid derivatives by using rare earth chlorides as claimed in claim 1, wherein the halogenated hydrocarbon includes but is not limited to methyl iodide, ethyl bromide, bromobenzene, 4-methyl bromobenzene, 4-methoxy iodobenzene, 4-chloro iodobenzene or 2, 4-dimethyl iodobenzene.
6. The method for catalytic synthesis of 5-substituted barbituric acid derivatives by using rare earth chlorides as claimed in claim 1, wherein the organic solvent includes but is not limited to methanol, ethanol or tetrahydrofuran.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114570382A (en) * | 2022-03-15 | 2022-06-03 | 上海城建职业学院 | Palygorskite/Mn-Cu composite catalyst and preparation method and application thereof |
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| CN108530368A (en) * | 2018-05-18 | 2018-09-14 | 大连正邦信息咨询有限公司 | The method of organic base catalytic barbiturates and diene dintrile addition reaction |
| CN108912057A (en) * | 2018-06-04 | 2018-11-30 | 河南大学 | A method of barbituric acid derivatives are replaced by amine catalytic air oxidation green syt 5- hydroxyl -5- alkyl two |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108530368A (en) * | 2018-05-18 | 2018-09-14 | 大连正邦信息咨询有限公司 | The method of organic base catalytic barbiturates and diene dintrile addition reaction |
| CN108912057A (en) * | 2018-06-04 | 2018-11-30 | 河南大学 | A method of barbituric acid derivatives are replaced by amine catalytic air oxidation green syt 5- hydroxyl -5- alkyl two |
Non-Patent Citations (2)
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| MANUELA MEUSEL ET AL.: "The Aminobarbituric Acid-Hydantoin Rearrangement", 《J. ORG. CHEM.》 * |
| 张源魁等: "稀土氯化物催化作用下纳米氢化钠对芳基卤化物的还原脱卤", 《催化学报》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114570382A (en) * | 2022-03-15 | 2022-06-03 | 上海城建职业学院 | Palygorskite/Mn-Cu composite catalyst and preparation method and application thereof |
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