阅读说明：本技术 一种脲类衍生物及其合成方法 (Urea derivative and synthetic method thereof ) 是由 赵育磊 司志姚 郭旭强 胡雅楠 孙莹 董永平 高博文 卢旭 武博翰 成倩倩 臧青 于 2019-11-05 设计创作，主要内容包括：本发明公开了一种脲类衍生物及其合成方法,该合成方法以胺类化合物为原料,加入胺类催化剂,然后向反应瓶中通入二氧化碳气体,在二氧化碳气体的氛围下,向反应瓶中依次加入溶剂、氢硅烷、路易斯酸性催化剂,通过一锅法反应催化合成得到如式(I)所示的脲类衍生物。本发明制备方法具有反应条件温和、原料、胺类催化剂及路易斯酸性催化剂简单易得、底物普适性好、后处理简便、收率良好等优点。本发明还公开了式(I)所示脲类衍生物在合成及药物化学领域的应用。(The invention discloses a urea derivative and a synthesis method thereof, wherein the synthesis method comprises the steps of taking an amine compound as a raw material, adding an amine catalyst, introducing carbon dioxide gas into a reaction bottle, sequentially adding a solvent, hydrosilane and a Lewis acid catalyst into the reaction bottle in the atmosphere of the carbon dioxide gas, and carrying out reaction and catalytic synthesis by a one-pot method to obtain the urea derivative shown in the formula (I). The preparation method has the advantages of mild reaction conditions, simple and easily obtained raw materials, amine catalysts and Lewis acid catalysts, good substrate universality, simple and convenient post-treatment, good yield and the like. The invention also discloses application of the urea derivative shown in the formula (I) in the fields of synthesis and medicinal chemistry.)

1. A synthetic method of urea derivatives is characterized by comprising the following specific steps:

adding an amine catalyst into an amine compound serving as a raw material, introducing carbon dioxide gas into a reaction bottle, sequentially adding a solvent, hydrosilane and a Lewis acid catalyst into the reaction bottle in the atmosphere of the carbon dioxide gas, and carrying out reaction and catalytic synthesis by a one-pot method to obtain the urea derivative shown in the formula (I);

the reaction process is shown as the formula (II):

in the formula (II), R is aryl or alkyl substituent;

the hydrosilane is one of phenyl silane and triethoxy silane.

2. The method of claim 1, wherein the carbon dioxide gas has a purity of greater than 99.9%.

3. The method of claim 1, wherein the amine catalyst is one or more of 1,5, 7-triazabicyclo (4.4.0) dec-5-ene and 4-dimethylaminopyridine.

4. The method of claim 1, wherein the Lewis acid catalyst is FeCl₃One or more of boron trifluoride diethyl etherate and ferric trifluoromethanesulfonateAnd (4) a plurality of.

5. The method for synthesizing a urea derivative according to claim 1, wherein the amine compound: carbon dioxide: hydrosilane: amine catalysts: the molar ratio of the lewis acidic catalyst is 1: (1-2): (1-2): (0.1-0.5): (0.1-0.5).

6. The method for synthesizing a urea derivative as claimed in claim 1, wherein the solvent is one or more of tetrahydrofuran, acetonitrile and 1, 4-dioxane.

7. The method as claimed in claim 1, wherein the reaction temperature is 100-120 ℃.

8. The method for synthesizing a urea derivative as claimed in claim 1, wherein the reaction time is 24-48 h.

9. A urea derivative prepared by the method for synthesizing a urea derivative according to any one of claims 1 to 8, characterized in that the structure thereof is represented by formula (I):

in the formula (I), the compound is shown in the specification,

r is aryl or alkyl substituent.

Technical Field

The invention belongs to the field of organic compound synthesis, and particularly relates to a urea derivative and a synthesis method thereof.

Background

Urea derivatives are widely used in pesticide chemistry, polymer science, analytical chemistry, biological research, and the like. More recently, sulfonylureas have been used to treat type II diabetes. Urea derivatives are also used in the preparation of lactone derivatives of bacterial inhibitors. In addition, macromolecular urea can be used as a precursor for guanidine ligands, while anionic urea is used for ring-opening polymerization and organic catalysis of materials. The synthesis of urea generally uses phosgene or its analogues, a highly toxic reagent. Carbon dioxide has attracted some attention as a raw material for urea synthesis, for example: (a) xu, A.R.Jupp, D.W.Stephan, Angew.chem.Int.Ed.2017,56,14277-₂Util.2017,21,553–561.(g)M.J.Fuchter,C.J.Smith,M.W.S.Tsang,A.Boyer,S.Saubern,J.H.Ryan,A.B.Holmes,Chem.Commun.2008,2152–2154。

However, the synthesis of the urea compound in the prior art has the defects of needing precious metal catalysis and needing to carry out reaction at high temperature (130-170 ℃) and high pressure (14-140 atm.).

Disclosure of Invention

The invention aims to provide a urea derivative and a synthesis method thereof, and provides a synthesis method of the urea derivative, which is characterized in that an amine catalyst and a cheap Lewis acid catalyst are jointly catalyzed, the raw materials are cheap and easy to obtain, and the synthesis method is environment-friendly.

The invention also provides a synthetic method of the urea derivative, which comprises the following specific steps: adding an amine catalyst into an amine compound serving as a raw material, introducing carbon dioxide gas into a reaction bottle, sequentially adding a solvent, hydrosilane and a Lewis acid catalyst into the reaction bottle in the atmosphere of the carbon dioxide gas, and carrying out reaction and catalytic synthesis by a one-pot method to obtain the urea derivative shown in the formula (I);

the reaction process is shown as the formula (II):

in the formula (II), R is aryl or alkyl substituent;

the hydrosilane is one of phenyl silane and triethoxysilane.

Preferably, the purity of the carbon dioxide gas is greater than 99.9%.

Preferably, the amine catalyst is one or more of 1,5, 7-triazabicyclo (4.4.0) dec-5-ene (TBD) and 4-dimethylaminopyridine.

Preferably, the amine catalyst is 1,5, 7-triazabicyclo (4.4.0) dec-5-ene (TBD).

Preferably, the Lewis acidic catalyst is FeCl₃One or more of boron trifluoride diethyl etherate and ferric trifluoromethanesulfonate.

Preferably, the Lewis acidic catalyst is FeCl₃。

Preferably, the amine compound: carbon dioxide: hydrosilane: amine catalysts: the molar ratio of the lewis acidic catalyst is 1: (1-2): (1-2): (0.1-0.5): (0.1-0.5).

Preferably, the solvent is one or more of Tetrahydrofuran (THF), acetonitrile, 1, 4-dioxane.

Preferably, the solvent is Tetrahydrofuran (THF).

Preferably, the temperature of the reaction is 100-120 ℃,

preferably, the reaction temperature is 110 ℃.

Preferably, the reaction time is 24-48 h.

The invention provides a urea derivative, which is prepared by a synthesis method of the urea derivative and has a structure shown in a formula (I):

in the formula (I), R is an alkyl substituent or an aryl substituent.

The invention also provides application of the urea derivative in the fields of synthesis and medicinal chemistry.

In one embodiment, the preparation method of the invention uses phenylsilane as an additive, and uses 1,5, 7-triazabicyclo (4.4.0) dec-5-ene (TBD) and FeCl₃As a catalyst, as shown in the following reaction formula (II):

wherein R is an alkyl substituent or an aryl substituent.

Wherein the amine compound: carbon dioxide: phenyl silane: 1,5, 7-triazabicyclo (4.4.0) dec-5-ene (TBD): FeCl₃In a molar ratio of 1: 1.4: 1.5: 0.1: 0.1.

wherein the solvent is Tetrahydrofuran (THF).

Wherein the reaction temperature is 110 ℃.

Wherein the reaction time is 24 h.

In one embodiment, the present invention provides a method for synthesizing a urea derivative comprising: adding 1,5, 7-triazabicyclo (4.4.0) dec-5-ene (TBD) and amine compound into a reaction bottle, introducing carbon dioxide gas into the reaction bottle, and sequentially adding solvent, hydrosilane and FeCl into the reaction bottle in the atmosphere of the carbon dioxide gas₃Reacting at 110 deg.c for 24 hr, and purifying to obtain the urea derivative in the formula (I).

The invention has the beneficial effects that: according to the synthetic method of the urea derivative, the amine compound and the carbon dioxide gas which are raw materials are cheap and easy to obtain, and the urea derivative is simple to synthesize through the combined catalysis of the small organic molecules and the Lewis acid. The urea derivative with excellent yield is obtained by taking three components of an amine compound, carbon dioxide gas and hydrosilane as raw materials and reacting by a one-pot method. The reaction substrate has good universality, simple and convenient post-treatment and environmental friendliness.

Detailed Description

In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.