CN112920089B - Method for synthesizing substituted urea compound by photocatalysis - Google Patents

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing substituted urea compounds by photocatalysis. The method specifically comprises the following steps: mixing tetrahalomethane with a solvent, adding an amine compound and a catalyst in sequence, stirring and reacting under the oxygen-containing atmosphere and the illumination condition, and separating and purifying to obtain a substituted urea compound; the synthetic method has wide sources of raw materials, the byproducts produced after the reaction are halogen simple substances, the added value is high, on one hand, the use of phosgene, triphosgene and the like with high toxicity as raw materials is avoided, on the other hand, a large amount of waste is avoided, the catalyst can be recycled, the influence of the preparation process on the environment is reduced, and the atomic utilization rate of the reaction is improved.

Description

Method for synthesizing substituted urea compound by photocatalysis

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing substituted urea compounds by photocatalysis.

Background

Substituted urea is an important fine chemical and is widely applied to industries such as industry, agriculture, pharmacy and the like. The structural unit of the substituted urea contains different substituted peptide bonds, so that the substituted urea has excellent biological activity and plays a role in the fields of medicine and biology. The substituted urea not only has important application in weeding, plant growth regulation, disinsection, sterilization, plant virus resistance and the like, but also can be used for preparing medicines and dyes, and can be used as additive of petroleum, hydrocarbon fuel and polymers, such as corrosion inhibitor, antioxidant, anti-settling agent and the like.

The synthesis method of the substituted urea compound mainly comprises the following steps: phosgene method, triphosgene method, ethyl chloroformate method, azide method, carbon monoxide carbonylation method, N-substituted trichloroacetanilide method, N-butyl m-ketoanilide method, nitroamine formylation method, etc. The conventional method for industrially synthesizing substituted urea is to obtain substituted urea by addition of isocyanate and amine by using phosgene or a phosgene-based isocyanate method. Although the phosgene method is practical, the preparation of phosgene is easy and low in cost, the phosgene is extremely toxic and has great harm to people and environment. The azide compound is easy to explode, the control difficulty of the operation process is high, the danger is high, isocyanate needs to be synthesized in the reaction process, however, the isocyanate is easy to have side reaction with water, alcohol and other compounds containing active hydrogen in the reaction system, and the toxicity is high, and the transportation and the storage are not easy. The carbon monoxide carbonylation method uses selenium, noble metals such as ruthenium, germanium, palladium and the like and compounds thereof as catalysts, and the reaction generally needs to be carried out at higher temperature and pressure, thus having higher cost. Patent CN104557618A discloses that N, N' -dialkyl urea is obtained by taking urea and benzyl alcohol as raw materials and reacting for several hours at 100-130 ℃ in a microwave reactor under the action of transition metal catalyst iridium complex, alkali and tertiary amyl alcohol. Patent CN201710413634.3 discloses that in solvent polyethylene glycol or aqueous solution of polyethylene glycol, under the action of alkali, iodide and oxidant, palladium catalyst is added to catalyze direct cross-coupling reaction of primary amine and carbon monoxide to prepare asymmetric disubstituted urea compound. Patent CN201811512934.8 discloses that N, N' -disubstituted urea compounds are prepared by reacting N-hydrocarboyloxyamides as raw materials with dichloro (p-methyl cumene) ruthenium (II) dimer complex as a catalyst in the presence of silver acetate. Patent CN201510734338.4 discloses that the ionic liquid loaded by superparamagnetic nano particles is used as a catalyst, aromatic amine and dimethyl carbonate react for 8-14 hours in a condensation way, and the corresponding N, N' -disubstituted urea derivative is obtained. Along with the continuous enhancement of environmental awareness, further development of a synthetic method of substituted urea compounds with simple reaction route, high efficiency, low cost and environmental friendliness is still needed.

Disclosure of Invention

Aiming at the technical problems existing in the prior art, the invention takes the organic amine compound and the tetrahalomethane as raw materials to directly react under the conditions of a catalyst and illumination to prepare the substituted urea compound, and has the advantages of wide raw material sources, short reaction time, simple and convenient operation, simple post-treatment process and high product yield.

The invention provides a method for synthesizing substituted urea compounds by photocatalysis, which specifically comprises the following steps:

mixing tetrahalomethane with a solvent, adding amine compounds shown in formulas I-III and a catalyst in sequence, stirring and reacting in an oxygen-containing atmosphere under illumination conditions, and separating and purifying to obtain substituted urea compounds shown in formulas IV-VI;

wherein ,

the R is ¹ Is C ₂ ～C ₂₀ Alkyl, C ₃ ～C ₂₀ Cycloalkyl, C ₃ ～C ₂₀ Alkylene, C ₃ ～C ₂₀ Alkynyl, C ₃ ～C ₂₀ Heterocyclyl, C ₅ ～C ₁₂ Heteroaryl or C ₆ ～C ₂₀ An aromatic group;

the R is ² 、R ³ H, C of a shape of H, C ₁ ～C ₂₀ Alkyl, C ₃ ～C ₂₀ Cycloalkyl, C ₃ ～C ₂₀ Alkylene, C ₃ ～C ₂₀ Alkynyl or C ₆ ～C ₂₀ An aromatic group;

the alkyl, cycloalkyl groups may be further monosubstituted by halogen, hydroxy, alkoxy or the like or different polysubstituted.

Further, the solvent is: toluene, benzene, N-hexane, benzotrifluoride, methylene chloride, dichloroethane, cyclohexane, methanol, ethanol, diethyl ether, isopropanol, butanol, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, chloroform, tetrachloromethane.

Further, the catalyst is one or more of manganic oxide, titanium dioxide, zinc oxide, tin oxide, zirconium dioxide, ferroferric oxide, tricobalt tetraoxide, cadmium sulfide and manganese dioxide.

Further, the reaction is carried out in the presence or absence of a base; the alkali is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, barium carbonate, calcium carbonate, lithium hydroxide, barium hydroxide, triethylamine, sodium tert-butyl alcohol, sodium ethoxide and sodium methoxide. .

Further, the molar ratio of the tetrahalomethane to the organic amine compound is 1:1.8-4.0.

Further, the illumination condition is specifically:

one or more of a light emitting diode, a xenon lamp, a mercury lamp and a metal halogen lamp are adopted as the light generating device for illumination.

Further, the stirring reaction time is 8-12h.

Further, the separation and purification specifically comprises:

and standing the stirred and reacted product for layering or filtering to obtain a filtrate layer, and removing the solvent from the filtrate layer to obtain the substituted urea compound.

The scheme of the invention has the following beneficial effects:

1) The invention takes organic amine and tetrahalomethane as raw materials and takes metal oxide as catalyst for catalytic preparation, the sources of the raw materials are wide, the byproducts generated after the reaction are halogen simple substances, the added value is high, on one hand, the use of phosgene, triphosgene and the like with high toxicity as raw materials is avoided, on the other hand, a large amount of waste is avoided, the catalyst can be recycled, the influence of the preparation process on the environment is reduced, and the atomic utilization rate of the reaction is improved.

2) The reaction condition of the invention is that the oxygen-containing atmosphere is an air condition and is carried out at normal temperature and pressure, the traditional heating and high-pressure conditions are replaced by adopting the illumination condition, the reaction condition is mild, the production safety is high, and the reaction cost is reduced.

3) The synthetic method of the substituted urea has good substrate applicability, mild process conditions, environment friendliness, simple process, simple and feasible operation method and contribution to popularization and application.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is an infrared spectrum of 1, 3-dinaphthyl urea provided by the embodiment of the invention;

FIG. 2 is an infrared spectrum of 1, 3-di-n-butyl urea provided by the embodiment of the invention;

FIG. 3 is an infrared spectrum of 1, 3-difurfuryl urea provided by the embodiment of the invention;

FIG. 4 is a mass spectrum of 1, 3-dibenzyl urea provided by the embodiment of the invention;

FIG. 5 is a mass spectrum of 1, 3-dinaphthyl urea provided by an embodiment of the present invention;

FIG. 6 is a mass spectrum of 1, 3-difurfuryl urea provided by the embodiment of the invention;

FIG. 7 is a mass spectrum of 1, 3-di-n-octylurea provided by an embodiment of the present invention;

FIG. 8 is a mass spectrum of 1, 3-di-o-tolylurea provided in the example of the present invention.

Detailed Description

In order to make the technical problems, technical solutions and advantages to be solved by the present invention more apparent, the following detailed description will be given with reference to the accompanying drawings and specific embodiments, but the scope of the present invention is not limited to the following specific embodiments.

Unless defined otherwise, all technical and scientific terms used hereinafter have the same meaning as commonly understood by one of ordinary skill in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the scope of the present invention.

Unless otherwise specifically indicated, the various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or may be prepared by existing methods.

In the embodiment of the invention, taking the formula I and tetrahalomethane as examples, the reaction shown as the formula (1) occurs under the action of illumination and a catalyst. The tetrahalomethane forms carbon free radicals and halogen free radicals under the illumination condition, the carbon free radicals react with electron-rich oxygen and react with amines to form urea compounds, and the halogen free radicals are combined pairwise to form halogen simple substances.

Specific examples are described further below.

Example 1

34.62 parts of carbon tetrabromide (content of 97%) is added into a reactor containing 100.00 parts of benzotrifluoride, 21.76 parts of benzylamine (content of 98.5%) is added, 0.31 part of trimanganese tetraoxide (99.5%) and 32.37 parts of cesium carbonate (content of 99.9%) are added, and under the irradiation of a Led lamp as a light source, stirring is carried out for 12 hours, then the mixture is allowed to stand for delamination, the upper layer is yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and toluene solvent is distilled and recovered from the upper layer solution, thus obtaining a light gray 1, 3-dibenzyl urea solid product.

Example 2

34.80 parts of carbon tetrabromide (content of 97.0%) is added into a reactor containing 100.00 parts of benzotrifluoride, 28.50 parts of 1-naphthylamine (content of 99.0%) is added, 0.31 parts of manganous oxide (99.5%) and 10.76 parts of sodium carbonate (content of 99.8%) are added, and after stirring reaction for 10 hours under the irradiation of a Led lamp as a light source, the mixture is allowed to stand for delamination, the upper layer is yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and the benzotrifluoride solvent is distilled and recovered from the upper layer solution, so that a gray black 1, 3-dinaphthyl urea solid product is obtained.

Example 3

34.48 parts of carbon tetrabromide (the content is 97.0%) is added into a reactor containing 85.00 parts of toluene, 14.78 parts of n-butylamine (the content is 99.0%) is added, 0.31 part of manganomanganic oxide (99.5%) and 10.88 parts of sodium carbonate (the content is 99.8%) are added, and under the irradiation of a xenon lamp serving as a light source, stirring reaction is carried out for 10 hours, then the mixture is stood for layering, the upper layer is light yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and toluene solvent is distilled and recovered from the upper layer solution, so that a yellow-brown 1, 3-di-n-butyl urea solid product is obtained.

Example 4

34.52 parts of carbon tetrabromide (content: 97.0%) was charged into a reactor containing 85.00 parts of toluene, 26.11 parts of n-octylamine (content: 99.0%) was added, 0.30 parts of trimanganese tetraoxide (99.5%) and 10.83 parts of sodium carbonate (content: 99.8%) were further added, and after stirring and reaction for 10 hours under irradiation of a xenon lamp as a light source, toluene solvent was recovered by distillation to obtain a yellowish 1, 3-di-n-octylurea solid product.

Example 5

15.54 parts of carbon tetrachloride (content: 99.0%) is added into a reactor containing 85.00 parts of benzotrifluoride, 19.62 parts of furfuryl amine (content: 99.0%) is added, 0.29 parts of titanium dioxide (99%) and 32.08 parts of cesium carbonate (content: 99.9%) are added, and after stirring and reacting for 10 hours under the irradiation of a xenon lamp as a light source, chlorine generated in the reaction process is collected, and the obtained oily solution is distilled to recover benzotrifluoride solvent, thereby obtaining a dark brown 1, 3-difurfuryl urea liquid product.

Example 6

34.70 parts of carbon tetrabromide (the content is 99.5%) is added into a reactor containing 80.00 parts of toluene, 21.87 parts of o-methylaniline (the content is 98%), 0.50 part of manganese dioxide (98%) and 10.64 parts of sodium carbonate (the content is 99.8%) are added, and the mixture is stirred and reacted for 12 hours under the irradiation of a Led lamp as a light source, then the mixture is stood for layering, the upper layer is yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and toluene solvent is recovered by distilling the upper layer solution, so that a purple 1, 3-di-o-methoxyphenyl urea solid product is obtained.

Example 7

34.60 parts of carbon tetrabromide (the content is 97.0%) is added into a reactor containing 85.00 parts of toluene, 48.78 parts of diisooctylamine (the content is 99.0%) is added, 0.30 part of manganomanganic oxide (99.5%) and 10.76 parts of sodium carbonate (the content is 99.5%) are added, and under the irradiation of a xenon lamp serving as a light source, stirring and reacting are carried out for 10 hours, standing and layering are carried out, the upper layer is yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and toluene solvent is distilled and recovered from the upper layer solution, so that a brown 1, 3-tetraisooctylurea solid product is obtained.

Example 8

33.50 parts of carbon tetrabromide (content 99.0%) is added into a reactor containing 80.00 parts of normal hexane, 18.72 parts of aniline (content 99.5%) is added, 0.30 part of titanium dioxide (99.0%) and 11.50 parts of sodium carbonate (content 99.5%) are added, and after stirring and reacting for 10 hours under the irradiation of a xenon lamp as a light source, the mixture is stood for delamination, the upper layer is light yellow transparent liquid, the lower layer is red and black oily bromine simple substance, and toluene solvent is recovered by distilling the upper layer solution, so as to obtain a brown 1, 3-diphenyl urea solid product.

The resulting substituted urea product was weighed and its theoretical yield calculated from the amount of raw material added, and the yields were calculated, wherein the yields of the substituted urea prepared in examples 1 to 8 were 90%, 91%, 88%, 86%, 91%, 90%, 87% and 88%, respectively.

Structural characterization

After the obtained substituted urea compound is separated and purified, the structure characterization is carried out by adopting various characterization modes of mass spectrum and infrared spectrum, and the characterization results of the substituted urea compound obtained in the examples 1-6 are taken as examples.

The mass spectrum of 1, 3-dibenzyl urea obtained in example 1 is shown in FIG. 4, and the peak with a mass-to-charge ratio of 241.1335 in the spectrum is an [ M+H ] ion peak, and the MS of 1, 3-dibenzyl urea theory [ M+H ] is 241.1335.

The infrared spectrum of 1, 3-dinaphthyl urea obtained in example 2 is shown in FIG. 1, and the main characteristic peaks thereof are (cm-1): 3367.59 to N-H stretching vibration, 1623.77 to C=O stretching vibration, 1576.74 to N-H deformation vibration peak, 1513.85 to C=C stretching vibration, 768.98 to C-H in-plane deformation vibration peak. As shown in FIG. 5, the mass spectrum of 1, 3-dinaphthyl urea shows that the peak with the mass-to-charge ratio of 311.1177 is an [ M-H ] ion peak, and the MS of the theory [ M-H ] of 1, 3-dinaphthyl urea is 311.1190;

the infrared spectrum of 1, 3-di-n-butylurea obtained in example 3 is shown in FIG. 2, and the main characteristic peaks thereof are (cm-1): 3324.20 belonged to N-H stretching vibration peak, 2962.13, 2871.29 belonged to-CH 3 stretching vibration peak, 2933.68 belonged to-CH 2 stretching vibration peak, 1634.38 belonged to C=O stretching vibration, 1563.99 belonged to N-H deformation vibration peak, 1323.41 belonged to N-C-N stretching vibration peak.

The mass spectrum of 1, 3-di-n-octylurea obtained in example 4 is shown in FIG. 7, in which the peak having a mass-to-charge ratio of 363.2005 is [ M+Br ]]Ion peak, theory of 1, 3-di-n-octylurea [ M+Br ] ^- ]The MS of (2) is: 363.2016.

the IR spectrum of 1, 3-difurfuryl urea obtained in example 5 is shown in FIG. 3, and the main characteristic peaks thereof are (cm-1): 3395.55 to N-H stretching vibration peak, 1637.75 to C=O stretching vibration peak, 1561.09 to N-H deformation vibration peak, 1401.99 to C=C ring stretching vibration peak, 1347.99 to N-C-N stretching vibration peak. The mass spectrum of 1, 3-difurfuryl urea is shown in FIG. 6, the peak with the mass-to-charge ratio of 221.0927 is an [ M+H ] ion peak, and the MS of the theory of 1, 3-difurfuryl urea [ M+H ] is 221.0921.

The mass spectrum of 1, 3-di-o-methoxyphenyl urea obtained in example 6 is shown in FIG. 8, wherein the peak with mass-to-charge ratio 273.1232 in the spectrum is [ M+Br- ] ion peak, and the MS of 1, 3-di-o-methoxyphenyl urea theory [ M+H ] is 273.1234.

While the foregoing is directed to the preferred embodiments of the present invention, it will be appreciated by those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the present invention.

Claims (5)

1. A method for photocatalytic synthesis of substituted urea compounds, which is characterized by comprising the following steps:

mixing tetrahalomethane with a solvent, adding amine compounds shown in formulas I-III and a catalyst in sequence, stirring and reacting in an oxygen-containing atmosphere under illumination conditions, and separating and purifying to obtain substituted urea compounds shown in formulas IV-VI; the illumination conditions are specifically as follows:

one or more than one of a light emitting diode, a xenon lamp and a metal halogen lamp is adopted as a light generating device for illumination; the catalyst is one or more of manganous oxide, titanium dioxide and manganese dioxide;

wherein ,

the R is ¹ Is C ₂ ～C ₂₀ An alkyl group;

the R is ² 、R ³ Is H;

the alkyl groups may be further monosubstituted with halogen, hydroxy or the same or different polysubstituted;

the reaction is carried out in the presence of a base; the alkali is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, sodium hydroxide and potassium hydroxide.

2. The method for photocatalytic synthesis of substituted urea compounds according to claim 1, wherein the solvent is: toluene, benzene, N-hexane, benzotrifluoride, methylene chloride, dichloroethane, cyclohexane, methanol, ethanol, diethyl ether, isopropanol, butanol, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, chloroform, tetrachloromethane.

3. The method for photocatalytic synthesis of substituted urea according to claim 1, wherein the molar ratio of tetrahalomethane to organic amine compound is 1:1.8-4.0.

4. The method for photocatalytic synthesis of substituted urea according to claim 1, wherein the stirring reaction time is 8-12 hours.

5. The method for synthesizing the substituted urea compound by photocatalysis according to claim 1, wherein the separation and purification specifically comprises:

and standing the stirred and reacted product for layering or filtering to obtain a filtrate layer, and removing the solvent from the filtrate layer to obtain the substituted urea compound.

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