Synthesis method for preparing urea from carbamate derivative, urea compound and application

Abstract

The invention provides a synthesis method for preparing urea from carbamate derivatives, a urea compound and application. The synthesis method is a novel method for preparing the urea compound through the reaction of carbamate and amine, the exchange reaction of aryl substituted methyl carbamate and amine is realized innovatively through the concerted catalysis strategy of light and copper, and the urea compound is efficiently generated. The reaction conditions are mild, the target product yield is high, and the universality is good. The method is expected to be expanded to a degradation reaction system of polyurethane compounds, and provides important technical support for solving the traditional polyurethane degradation problem and reducing the environmental pollution risk caused by the polyurethane degradation problem.

Description

Technical Field

[0001] This invention relates to the field of compound synthesis technology, specifically to a method for preparing urea from carbamate derivatives, urea compounds, and their applications. Background Technology

[0002] Urea compounds (containing the urea group -NH-CO-NH- in their molecular structure) are a class of compounds with wide-ranging applications, their importance manifesting in multiple fields such as agriculture, medicine, materials science, and industry. Firstly, urea compounds are key intermediates in the synthesis of heterocyclic compounds (such as pyrimidines and triazines), serving as cornerstone raw materials for the synthesis of natural products and drug molecules. In agriculture, the urea group structure is also an important structural unit in highly effective fungicides and herbicides. In medicine, the chemical properties of the urea group (such as its hydrogen bonding ability and specific binding to biological targets) make it an important structural unit in drug design, and many urea compounds have been developed into clinical drugs. In polymer processing, urea compounds can act as plasticizers or stabilizers, improving the flexibility and anti-aging properties of materials. In environmental monitoring, urea compounds can specifically bind to specific pollutants (such as heavy metal ions and pesticide residues), enabling rapid detection of pollutants in environmental samples (e.g., using test strips and sensors).

[0003] The synthesis of classic urea compounds mainly includes two methods: the first is to generate urea compounds through addition reactions of simple amines and isocyanates; the second is to generate urea compounds through condensation reactions of amines and phosgene (or its derivatives). Both methods are sensitive to water and humidity, prone to side reactions, and phosgene is toxic and difficult to handle. Therefore, the exchange reaction between carbamates and amines has become the preferred strategy for laboratory synthesis of urea. Currently, the above exchange strategy generally requires highly reversible reactions, makes it difficult to advance chemical equilibrium towards the target direction, and results in numerous side reactions, difficulty in controlling product purity, and high temperature requirements.

[0004] Therefore, it is urgent to develop novel catalytic systems to achieve the exchange reaction of carbamates and amines to produce urea compounds under mild conditions. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a method for synthesizing urea from carbamate derivatives, urea compounds, and their applications.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] This invention provides a method for synthesizing urea from carbamate derivatives. The method includes: adding an aryl-substituted carbamate, an aromatic amine, a copper catalyst, and a ligand to a solvent and stirring; then irradiating the solvent with an LED lamp for 2–8 hours to obtain a urea compound; wherein the aryl-substituted carbamate has the following structural formula: The system also applies to benzene rings with one or more substituents selected from phenyl, methyl, methoxy, fluorine, chlorine, bromine, iodine, ester, cyano, and nitro groups, as well as 1-naphthyl, 2-naphthyl, 2-furanyl, 2-thienyl, and 2-pyridyl groups, i.e., benzene rings with two or more substituents. The structural formula of aromatic amines is Ar. 2 NH2, where Ar 2 This system is applicable to benzene rings that are phenyl or have one or more substituents selected from methyl, methoxy, fluorine, chlorine, bromine, iodine, ester, cyano, and nitro groups, as well as 1-naphthyl, 2-naphthyl, 2-furanyl, 2-thienyl, and 2-pyridyl groups, i.e., benzene rings that can have two or more substituents.

[0008] The reaction equation for this synthesis method is:

[0009]

[0010] Furthermore, the molar ratio of the aryl substituted carbamate to the aromatic amine is 1:(1.1 to 1.5).

[0011] Furthermore, the copper catalyst includes one or more of cuprous chloride, cuprous bromide, cuprous iodide, cuprous thiocyanate, copper acetate, copper chloride, copper trifluoromethanesulfonate, copper tetraethyl cyanophosphate, copper tetrafluoroborate, and cuprous thiophene dicarboxylate.

[0012] Furthermore, the ligand comprises one or more of the following: bipyridine, 4,4-di-tert-butylbipyridine, o-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline, 3,8-dibromophenanthroline, 4,7-dichloro-1,10-phenanthroline, 2,9-diphenyl-1,10-phenanthroline, 3,5,6,8-tetrabromo-1,10-phenanthroline, 2,9-bis(pyridin-2-yl)-1,10-phenanthroline, 2,9-dibromo-1,10-phenanthroline-5,6-dione, 1,3-dimesimetrimethylimidazolium-2-yl (IMes), or 1,3-bis(2,6-diisopropylphenyl)imidazolium-2-yl (SIPr).

[0013] Furthermore, the solvent is selected from one of methanol, ethanol, dichloromethane, dichloroethane, 1,4-dioxane, acetonitrile, toluene, tetrahydrofuran, dimethyl sulfoxide, ethyl acetate, and water.

[0014] Furthermore, the concentration of the solvent is 0.1–1 mol / L.

[0015] Furthermore, the light source wavelength of the LED lamp includes 365nm, 390nm, 420nm or 465nm.

[0016] Furthermore, the synthesis method includes: after the step of irradiating with an LED lamp for 2 to 8 hours, separating the resulting solution by column chromatography to obtain the urea compound.

[0017] This invention also provides a urea compound obtained by the above-mentioned method for preparing urea from carbamate derivatives, wherein the structural formula of the urea compound is as follows:

[0018] This invention provides an application of the above-mentioned urea compounds in the fields of agriculture, medicine, polymer processing, and environmental monitoring.

[0019] Compared with the prior art, the technical solution provided by the present invention has at least the following advantages:

[0020] This invention provides a synthetic method for preparing urea from carbamate derivatives, urea compounds, and their applications. This synthetic method is a novel approach to prepare urea compounds from the reaction of carbamates with amines. It innovatively utilizes a synergistic catalytic strategy of light and copper to achieve the exchange reaction between aryl-substituted methyl carbamates and amines, efficiently generating urea compounds. The reaction conditions are mild, the target product yield is high, and the method has good versatility. This method is expected to be extended to the degradation reaction system of polyurethane compounds, providing important technical support for solving the traditional degradation problems of polyurethane and reducing the environmental pollution risks it poses. Attached Figure Description

[0021] Figure 1 This is the proton spectrum of compound 1 prepared in Example 1 of this invention;

[0022] Figure 2 This is the carbon spectrum of compound 1 prepared in Example 1 of this invention. Detailed Implementation

[0023] The present invention will now be described in detail with reference to specific embodiments.

[0024] Example 1

[0025] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 1 with the following structural formula:

[0026]

[0027] The synthetic steps are as follows: A magnetic flask containing phenylcarbamate (0.3 mmol), aniline (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) was added to a 10 mL round-bottom flask. The flask was then stoppered with a rubber stopper, purged three times with nitrogen, and then toluene (1 mL) was added. The mixture was irradiated with an LED lamp for 8 hours. After the reaction was complete, the product was purified by rapid silica gel column chromatography using petroleum ether / ethyl acetate as the mobile phase. The resulting urea compound, compound 1, was obtained. Its 1H NMR spectrum is shown below. Figure 1 As shown, the carbon spectrum is as follows Figure 2 As shown.

[0028] The yield of this method is 84%. The structural characterization of compound 1 is as follows: white solid. 11 H NMR (400MHz, DMSO) δ8.67 (s, 2H), 7.46 (d, J = 8.4Hz, 4H), 7.28 (t, J = 8.0Hz, 4H), 6.97 (t, J = 7.6Hz, 2H). 13 C NMR (100MHz, DMSO) δ153.0, 140.2, 129.2, 122.3, 118.7ppm.

[0029] Table 1 shows the reaction results using other reaction ratios, as well as catalysts, ligands, light exposure time, and reaction concentrations.

[0030]

[0031]

[0032] Example 2

[0033] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 2 with the following structural formula:

[0034]

[0035] The synthesis steps are as follows: A magnetic flask, p-toluenecarbamate (0.3 mmol), p-toluidine (0.33 mmol), cuprous thiophenecarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added. The mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 2, was obtained by rapid silica gel column chromatography.

[0036] The yield of this method is 82%. The structural characterization of compound 2 is as follows: white solid.11 H NMR (400MHz, DMSO) δ8.47(s,2H),7.33(d,J=8.0Hz,4H),7.07(d,J=8.0Hz,4H),2.24(s,6H). 13 C NMR (100MHz, DMSO) δ152.7, 137.3, 130.6, 129.2, 118.3, 20.4ppm.

[0037] Example 3

[0038] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 3 with the following structural formula:

[0039]

[0040] The synthesis steps are as follows: A magnetic flask, phenylcarbamate (0.3 mmol), p-methylaniline (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added. The mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 3, was obtained by rapid silica gel column chromatography.

[0041] The yield of this method is 83%. The structural characterization of compound 3 is as follows: white solid. 11 H NMR (400MHz, DMSO) δ8.59(s,1H),8.52(s,1H),7.45(d,J=8.0Hz,2H),7.34(d,J=8.4Hz ,2H),7.27(t,J=8.0Hz,2H),7.08(d,J=8.0Hz,2H),6.95(t,J=7.6Hz,1H),2.24(s,3H). 13 C NMR (100MHz, DMSO)δ

[0042] 152.6,139.9,137.2,130.7,129.2,128.8,121.7,118.4,118.2,20.4ppm.

[0043] Example 4

[0044] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 4, whose structural formula is as follows:

[0045]

[0046] The synthesis steps are as follows: A magnetic flask, p-tolyl carbamate (0.3 mmol), p-methoxyaniline (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 h. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 4, was obtained by rapid silica gel column chromatography.

[0047] The yield of this method is 88%. The structural characterization of compound 4 is as follows: white solid. 11 H NMR (400MHz, DMSO) δ8.44(s,1H),8.40(s,1H),7.29-7.39(m,4H),7.07(d,J=8.4Hz,2H),6.86(d,J=8.8Hz,2H),3.71(s,3H),2.24(s,3H). 13 C NMR (100MHz, DMSO) δ154.5,152.9,137.4,132.9,130.5,129.2,120.0,118.3,114.0,56.2,20.4ppm.

[0048] Example 5

[0049] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 5, whose structural formula is as follows:

[0050]

[0051] The synthesis steps are as follows: A magnetic ball, p-toluenecarbamate (0.3 mmol), p-fluoroaniline (0.33 mmol), cuprous thiophenecarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound 5, i.e., compound 5, was obtained by rapid silica gel column chromatography.

[0052] This method yields 80% of the product. The structural characterization of compound 5 is as follows: white solid. 11H NMR (400MHz, DMSO) δ8.63 (s, 1H), 8.52 (s, 1H), 7.42-7.50 (m, 2H), 7.34 (d, J = 8.4Hz, 2H), 7.05-7.15 (m, 4H), 2.24 (s, 3H). 13 C NMR (100MHz, DMSO) δ 157.4 (d, J = 237.9Hz), 152.8, 137.5, 136.2 (d, J = 2.3Hz), 130.7, 129.2, 120.0 (d, J = 7.6Hz), 115.3 (d, J = 22.0Hz), 20.4ppm.

[0053] Example 6

[0054] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 6, whose structural formula is as follows:

[0055]

[0056] The synthesis steps are as follows: A magnetic flask, p-toluenecarbamate (0.3 mmol), p-chloroaniline (0.33 mmol), cuprous thiophenecarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 6, was obtained by rapid silica gel column chromatography.

[0057] This method yields 82% of the product. The structural characterization of compound 6 is as follows: white solid. 11 H NMR (400MHz, DMSO) δ8.74(s,1H),8.56(s,1H),7.48(d,J=8.8Hz,2H),7.27-7.37(m,4H),7.08(d,J=8.4Hz,2H),2.24(s,3H). 13 C NMR (100MHz, DMSO) δ152.5,138.9,137.0,130.9,129.2,128.6,125.3,119.7,118.4,20.4ppm.

[0058] Example 7

[0059] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 7 with the following structural formula:

[0060]

[0061] The synthesis steps are as follows: A magnetic flask, p-tolyl carbamate (0.3 mmol), m-chloroaniline (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 7, was obtained by rapid silica gel column chromatography.

[0062] The yield of this method is 83%. The structural characterization of compound 7 is as follows: white solid. 11 H NMR(400MHz,DMSO)δ8.81(s,1H),8.61(s,1H),7.71(s,1H),7.34(d,J=8.0Hz,2H ),7.23-7.31(m,2H),7.09(d,J=8.0Hz,2H),7.00(d,J=6.8Hz,2H),2.24(s,3H). 13 C NMR (100MHz, DMSO) δ153.4,142.6,137.7,133.2,131.0,130.4,129.2,121.4,118.6,117.6,116.6,20.3ppm.

[0063] Example 8

[0064] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 8, whose structural formula is as follows:

[0065]

[0066] The synthesis steps are as follows: A magnetic flask, p-toluylcarbamate (0.3 mmol), ethyl m-aminobenzoate (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 8, was obtained by rapid silica gel column chromatography.

[0067] The yield of this method is 78%. The structural characterization of compound 8 is as follows: white solid. 11H NMR (400MHz, DMSO) δ8.88(s,1H),8.55(s,1H),8.15(s,1H),7.63-7.67(m,1H),7.56(d,J=8.0Hz,1H),7.41(t,J=8. 0Hz,1H),7.35(d,J=8.0Hz,2H),7.09(d,J=8.0Hz,2H),4.31(q,J=7.2Hz,2H),2.24(s,3H),1.32(t,J=7.2Hz,3H),. 13 C NMR (100MHz, DMSO) δ166.8,152.6,140.3,137.0,129.2,122.4,118.6,60.8,20.4,14.2ppm.

[0068] Example 9

[0069] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 9, whose structural formula is as follows:

[0070]

[0071] The synthesis steps are as follows: A magnetic flask, p-tolyl carbamate (0.3 mmol), o-bromo-p-methylaniline (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added, and the mixture was irradiated with an LED lamp for 8 h. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 9, was obtained by rapid silica gel column chromatography.

[0072] The yield of this method is 86%. The structural characterization of compound 9 is as follows: white solid. 11 H NMR(400MHz,DMSO)δ9.27(s,1H),7.99(s,1H),7.89-7.96(m,1H),7.42(s,1H),7.31-7.39(m,2H),7.05-7.15(m,3H),2.24(s,6H), 13 C NMR (100MHz, DMSO) δ152.4,137.1,134.7,133.5,132.5,130.9,129.3,128.6,122.2,118.3,113.0,20.4,19.9ppm.

[0073] Example 10

[0074] This invention provides a method for synthesizing urea from a carbamate derivative, yielding compound 10 with the following structural formula:

[0075]

[0076] The synthesis steps are as follows: A magnetic flask, p-tolyl carbamate (0.3 mmol), 2-naphthylamine (0.33 mmol), cuprous thiophene dicarboxylate (0.015 mmol), and 4,7-dimethyl-1,10-phenanthroline (0.018 mmol) were added to a 10 mL round-bottom flask. The flask was then sealed with a rubber stopper. After purging with nitrogen three times, toluene (1 mL) was added. The mixture was irradiated with an LED lamp for 8 hours. After the reaction was completed, petroleum ether / ethyl acetate was used as the mobile phase, and the urea compound, namely compound 10, was obtained by rapid silica gel column chromatography.

[0077] The yield of this method is 88%. The structural characterization of compound 10 is as follows: white solid. 11 H NMR (400MHz, DMSO) δ8.87(s,1H),8.68(s,1H),8.14(s,1H),7.77-7.86(m,3H),7.50-7. 55(m,1H),7.39-7.47(m,3H),7.34(t,J=7.6Hz,2H),7.11(d,J=8.4Hz,2H),2.25(s,3H), 13 C NMR (100MHz, DMSO) δ152.8,137.6,137.2,133.9,130.8,129.3,129.1,128.4,127.5,127.0,126.4,123.9,119.7,118.5,113.4,20.4ppm.

[0078] Those skilled in the art will understand that the above embodiments are specific examples of implementing the present invention, and in practical applications, various changes in form and detail can be made without departing from the spirit and scope of the present invention. Any person skilled in the art can make their own modifications and alterations without departing from the spirit and scope of the present invention; therefore, the scope of protection of the present invention should be determined by the scope defined in the claims.

Claims

1. A synthetic method for preparing urea from a carbamate derivative, characterized by, The synthesis method comprises the following steps: stirring aryl-substituted carbamates, aromatic amines, copper catalysts and ligands in a solvent, irradiating with an LED lamp for 2-8 hours to obtain urea compounds. The aryl-substituted urethane has a structural formula of wherein Ar 1 is a phenyl ring and a methyl, methoxy, fluorine, chlorine, bromine, iodine, ester group, cyano, nitro group, or a phenyl ring substituted with one or more of the above groups, a 1-naphthyl group, a 2-naphthyl group, a 2-furyl group, a 2-thienyl group, a 2-pyridyl group; The structural formula of the aromatic amine is Ar 2 NH2, wherein Ar 2 is a phenyl ring and is substituted with one or more of a methyl group, a methoxy group, a fluorine, a chlorine, a bromine, an iodine, an ester group, a cyano group, a nitro group, a 1-naphthyl group, a 2-naphthyl group, a 2-furyl group, a 2-thienyl group, a 2-pyridyl group.

2. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The molar ratio of the aryl-substituted carbamates to the aromatic amines is 1:(1.1-1.5).

3. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The copper catalysts comprise one or more of cuprous chloride, cuprous bromide, cuprous iodide, cuprous thiocyanate, copper acetate, copper chloride, copper triflate, tetraethyl cyanide copper hexafluorophosphate, copper tetrafluoroborate, and cuprous thiophene dicarboxylate.

4. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The ligands comprise one or more of bipyridine, 4,4-di-tert-butyl bipyridine, phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline, 3,8-dibromophenanthroline, 4,7-dichloro-1,10-phenanthroline, 2,9-diphenyl-1,10-phenanthroline, 3,5,6,8-tetrabromo-1,10-phenanthroline, 2,9-bis(pyridin-2-yl)-1,10-phenanthroline, 2,9-dibromo-1,10-phenanthroline-5,6-dione, 1,3-di-mesityl imidazol-2-yl (IMes), or 1,3-bis(2,6-diisopropylphenyl)imidazoline-2-yl (SIPr).

5. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The solvent is selected from one of methanol, ethanol, dichloromethane, dichloroethane, 1,4-dioxane, acetonitrile, toluene, tetrahydrofuran, dimethyl sulfoxide, ethyl acetate, and water.

6. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The concentration of the solvent is 0.1-1 mol / L.

7. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The light source wavelength of the LED lamp comprises 365 nm, 390 nm, 420 nm, or 465 nm.

8. The process for the synthesis of urea from carbamate derivatives according to claim 1, characterized in that, The synthesis method comprises the following steps: after the step of irradiating with the LED lamp for 2-8 hours, the obtained solution is separated by column chromatography to obtain the urea compounds.

9. A urea compound produced by the method of producing urea according to any one of claims 1 to 8, characterized by, The structural formula of the urea compound is 10. The urea compounds according to claim 9 are used in the fields of agriculture, medicine, polymer processing, and environmental detection.

Images