Synthesis method of N, N '-disubstituted asymmetric urea and diuron

Abstract

The invention relates to the field of synthesis of asymmetric urea compounds, in particular to a synthesis method of N, N '-disubstituted asymmetric urea and diuron. According to the method disclosed by the invention, fatty primary amine and aromatic primary amine with steric hindrance at an alpha site are selected as reaction substrates, carbonyl sulfide is adopted as a carbonylation reagent, and a staged reaction is carried out, so that the selectivity of the target product N, N '-disubstituted asymmetric urea is further improved. According to the present invention, the high-selectivity synthesis of the N, N '-disubstituted asymmetric urea compound by using two primary amines, which is difficult to achieve by using other methods at present, is achieved, and the method is applied to the preparation of the pesticide diuron, such that the gram-level amplification reaction can still achieve the high yield and the high selectivity, and the strong industrial application value is provided.

Description

Technical Field

[0001] The present invention relates to the field of synthesis of asymmetric urea compounds, and more particularly to a method for synthesizing N,N'-disubstituted asymmetric urea and cypermethrin. Background Art

[0002] The existing preparation methods for synthesizing N,N'-disubstituted asymmetric ureas using two primary amines as substrates mainly use phosgene, isocyanate, urea, CO and CO2 as carbonylation reagents. Among these methods, the synthesis of asymmetric ureas using CO or CO2 as carbonylation reagents has become a research hotspot in recent years due to its high atomic utilization, green and efficient. However, the synthesis of asymmetric ureas using CO or CO2 as carbonylation reagents with two primary amines has the problems of low selectivity and harsh reaction conditions.

[0003] At present, a method for synthesizing asymmetric urea with high selectivity has been developed using carbonyl sulfide (COS) as a carbonylation reagent and aromatic primary amines and aliphatic secondary amines with low nucleophilicity as substrates. However, in a system using two primary amines as substrates to synthesize asymmetric urea, two symmetric urea byproducts are easily produced, resulting in a decrease in the selectivity of asymmetric urea, which is a difficulty in the synthesis of asymmetric urea.

[0004] Asymmetric urea compounds are widely used in the fields of pesticides and chemicals, especially N,N'-disubstituted asymmetric ureas, which have good biological activity. The pesticide cypermethrin is one of them. Therefore, the synthesis method of the pesticide cypermethrin, as an industrial product, needs to meet the requirements of high selectivity and high yield as well as industrialization. Summary of the invention

[0005] In order to further improve the selectivity of N,N'-disubstituted asymmetric urea compounds in the preparation process of asymmetric urea compounds, the present invention provides a method for synthesizing N,N'-disubstituted asymmetric urea.

[0006] The present invention selects aliphatic primary amines and aromatic primary amines with steric hindrance at the α position as reaction substrates, uses carbonyl sulfide as a carbonylation reagent, and performs a staged reaction, thereby further improving the selectivity of the target product N,N'-disubstituted asymmetric urea.

[0007] One of the purposes of the present invention is to provide a method for synthesizing N,N'-disubstituted asymmetric urea.

[0008] A method for synthesizing N,N'-disubstituted asymmetric urea, comprising: a primary amine compound I and a primary amine compound II, using carbonyl sulfide as a carbonylation reagent, and performing a two-stage reaction; the temperature of the second-stage reaction is higher than the temperature of the first-stage reaction;

[0009] The primary amine compound I is a fatty primary amine with steric hindrance at the α position; the fatty primary amine refers to a product in which one hydrogen atom in an ammonia molecule is replaced by a substituted or unsubstituted alkyl or cycloalkyl group; its chemical formula is: R 1 -NH2, R 1 is a substituted or unsubstituted alkyl or cycloalkyl group. The α position of the fatty primary amine refers to the position of the first carbon atom connected to the amino group. The fatty primary amine with steric hindrance at the α position is selected from 2-phenyl-2-propylamine, cyclohexylamine, and tert-butylamine. Among them, the structural formula of 2-phenyl-2-propylamine is: The position of the sphere in the structural formula is the α position.

[0010] The primary amine compound II is an aromatic primary amine, which is selected from aniline and p-methylaniline.

[0011] The reaction mechanism of the synthesis method of the N,N'-disubstituted asymmetric urea is as follows.

[0012]

[0013] The molar ratio of the primary amine compound I to the primary amine compound II can be selected in a wide range. As a preferred embodiment, the molar ratio of the primary amine compound I to the primary amine compound II is 1:1.5-3, more preferably 1:2-3, such as 1:2, 1:2.5, 1:3.

[0014] The molar ratio of carbonyl sulfide to primary amine compound I can be selected in a wide range. As a preferred embodiment, the molar ratio of carbonyl sulfide to primary amine compound I is 2-6:1, more preferably 3-6:1.

[0015] The first stage reaction temperature can be a conventional temperature for the two-step synthesis of asymmetric urea using carbonyl sulfide as a carbonylation reagent. As a preferred embodiment, the first stage reaction temperature is 20°C-35°C, such as 20°C, 25°C, 30°C, 35°C.

[0016] The first stage reaction time can be the conventional time of the two-step method for synthesizing asymmetric urea using carbonyl sulfide as the carbonylation reagent. As a preferred embodiment, the first stage reaction time is 2h-8h, such as 2h, 4h, 6h, 8h.

[0017] The second stage reaction temperature can be a conventional temperature for the two-step synthesis of asymmetric urea using carbonyl sulfide as a carbonylation agent. As a preferred embodiment, the second stage reaction temperature is 60-90°C, such as 60°C, 70°C, 80°C, 90°C.

[0018] The second stage reaction time can be the conventional time of the two-step method for synthesizing asymmetric urea using carbonyl sulfide as the carbonylation reagent. As a preferred embodiment, the second stage reaction time is 6h-24h, such as 6h, 8h, 12h, 24h.

[0019] The reaction can be carried out without a catalyst, that is, both the first stage reaction and the second stage reaction can be carried out without a catalyst.

[0020] The reaction is carried out in a solvent-free or polar aprotic solvent. That is, the first stage reaction and the second stage reaction can be carried out in a solvent-free condition or in a polar aprotic solvent. The polar aprotic solvent is selected from one or more of acetonitrile, N-methylpyrrolidone (NMP), and N,N-dimethylformamide (DMF).

[0021] The reaction is carried out under air-tight conditions. That is, both the first-stage reaction and the second-stage reaction can be carried out under air-tight conditions. Specifically, the air can be isolated by introducing a protective gas. The protective gas can be nitrogen.

[0022] After the reaction is completed, recrystallization or column chromatography separation can be performed to obtain the target product N,N'-disubstituted asymmetric urea; the end of the reaction refers to the end of the second stage reaction;

[0023] The recrystallization comprises: adding a solvent for crystallization and filtering, and the obtained crystal is the N,N'-disubstituted asymmetric urea;

[0024] The column chromatography separation comprises: neutralizing with an acidic solution, extracting with an extractant, drying the organic layer with a neutral drying agent, filtering, concentrating the filtrate under reduced pressure to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain the N,N'-disubstituted asymmetric urea.

[0025] After the synthesis method is industrialized, the target product can be obtained by recrystallization. Compared with column chromatography separation, the recrystallization method is simpler and can obtain a higher yield.

[0026] In a gram-scale reaction, the amount of N,N'-disubstituted asymmetric urea obtained by solvent recrystallization may be small, and the filtrate obtained by filtration during recrystallization needs to be further subjected to column chromatography to obtain more target product N,N'-disubstituted asymmetric urea. Therefore, the filtrate obtained by filtration during recrystallization can also be subjected to the column chromatography separation again.

[0027] The solvent used for the recrystallization is a solvent that can dissolve the N,N'-disubstituted asymmetric urea but cannot dissolve organic salt substances. The solvent can be selected from one or more of ethyl acetate and dichloromethane.

[0028] The extractant used in the column chromatography separation is a solvent that can dissolve the N,N'-disubstituted asymmetric urea but cannot dissolve organic salt substances. The extractant can be selected from one or more of ethyl acetate and dichloromethane.

[0029] If the reaction is carried out in a polar aprotic solvent, the volume ratio of the extractant to the polar aprotic solvent may be 1-3: 3. The extractants used in the two extractions may be the same or different.

[0030] The acidic solution is selected from one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid and perchloric acid.

[0031] The neutral desiccant may be selected from at least one of anhydrous magnesium sulfate, anhydrous calcium chloride, anhydrous copper sulfate, anhydrous calcium sulfate, anhydrous sodium sulfate, and aluminum oxide.

[0032] According to an embodiment disclosed in the present invention, a method for synthesizing N,N'-disubstituted asymmetric urea comprises: performing a two-stage reaction of 2-phenyl-2-propylamine, cyclohexylamine or tert-butylamine with aniline or p-methylaniline using carbonyl sulfide as a carbonylation reagent; the temperature of the second stage reaction is higher than the temperature of the first stage reaction;

[0033] The molar ratio of the primary amine compound I to the primary amine compound II is 1:2-3, and the molar ratio of the carbonyl sulfide to the primary amine compound I is 3-6:1;

[0034] The first stage reaction temperature is 20℃-35 ℃ The first stage reaction time is 2h-8h, the second stage reaction temperature is 60-90°C, and the second stage reaction time is 6h-24h. At this time, the yield of the N,N'-disubstituted asymmetric urea is 85-90% and the selectivity is 87-91%.

[0035] In the method for synthesizing N,N'-disubstituted asymmetric urea, when the substrate is 2-phenyl-2-propylamine or p-methylaniline, the synthesized N,N'-disubstituted asymmetric urea is cypermethrin. The structural formula of cypermethrin is

[0036] A method for synthesizing cypermethrin comprises: carrying out a two-stage reaction of 2-phenyl-2-propylamine, p-methylaniline and carbonyl sulfide as a carbonylation reagent;

[0037] The molar ratio of 2-phenylpropan-2-amine to p-toluidine is 1:2-3;

[0038] The molar ratio of carbonyl sulfide to -phenylpropan-2-amine is 3-6:1;

[0039] The reaction temperature of the first stage is 20°C-35°C, the reaction time of the first stage is 2h-8h, the reaction temperature of the second stage is 60-90°C, and the reaction time of the second stage is 6h-24h.

[0040] The reaction mechanism of the synthesis method of cypermethrin is as follows.

[0041]

[0042] in, The target product is thiamethoxam, As a by-product.

[0043] The specific reaction route of the synthesis method of cypermethrin is as follows.

[0044]

[0045] Compared with the prior art, the present invention has the following beneficial effects:

[0046] The present invention provides a method for synthesizing N,N'-disubstituted asymmetric urea by using two primary amines of specific structures as substrates and carbonyl sulfide as a carbonylation reagent through a two-stage reaction. The method realizes the highly selective synthesis of N,N'-disubstituted asymmetric urea compounds by two primary amines, which is difficult to achieve by other methods at present, and the method is applied to the preparation of the pesticide cypermethrin.

[0047] In the method of the present invention, the reaction of the fatty primary amine with COS to form symmetrical urea can be avoided as much as possible through the design of the substrate structure (selecting a fatty primary amine with steric hindrance at the α position of the amine and an aromatic primary amine with low reactivity), the adjustment of the substrate ratio, the regulation of the amount of carbonyl sulfide, and the staged reaction, thereby improving the selectivity of asymmetric urea. Under normal pressure conditions, the yield of asymmetric urea compounds can reach 90% and the selectivity can reach 91%. The technical problem of low selectivity in the reaction of synthesizing N,N'-disubstituted asymmetric urea using two primary amines as substrates is solved, and a new method for preparing the pesticide cypermethrin with high selectivity is developed by using the method.

[0048] The method of the invention does not require a catalyst and can react under normal pressure conditions, thereby reducing the preparation cost.

[0049] The method of the present invention can still achieve high yield and selectivity in a gram-scale scale-up reaction, and has strong industrial application value. DETAILED DESCRIPTION

[0050] The present invention is described in detail below in conjunction with specific embodiments. It is necessary to point out that the following embodiments are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made to the present invention by those skilled in the art based on the contents of the present invention still fall within the scope of protection of the present invention.

[0051] The reagents used in the following examples are all commercially available products.

[0052] Examples 1-6

[0053] N,N'-disubstituted unsymmetric ureas were prepared using 2-phenyl-2-propylamine and aniline as reaction substrates and COS as carbonylation reagent.

[0054] The preparation method is as follows:

[0055] 2-phenyl-2-propylamine (1 mmol), aniline (1.5-3 mmol), and acetonitrile (MeCN) (2 mL) were placed in a 15 mL stainless steel autoclave equipped with a magnetic stirrer; N2 was blown into the stainless steel autoclave to remove the air in the stainless steel autoclave. Subsequently, COS was introduced into the stainless steel autoclave so that the pressure of COS in the stainless steel autoclave was P. The stainless steel autoclave was placed in a 25°C constant temperature sand bath, reacted for 4 hours under stirring conditions, and then heated to 70°C and continued to react for 8 hours under stirring conditions.

[0056] After the reaction is completed, 0.5 mol / L of dilute hydrochloric acid aqueous solution is added to the reaction mixture solution to neutralize the unreacted amine in the reaction system until the reaction solution is neutral, and then extracted with ethyl acetate three times. The organic layers are combined, dried over anhydrous MgSO4, filtered, and the filtrate is concentrated under reduced pressure to obtain a crude product. The crude product is collected by silica gel column chromatography (PE / EA=20 / 1-1 / 1, v / v) gradient elution, and the eluent at a ratio of 4 / 1 is distilled under reduced pressure to remove the eluent to obtain a white solid product.

[0057] The prepared white solid product mp = 175-177 ° C; 1 H NMR(500MHz, CDCl3)δ7.48(d,J=8.1Hz,2H),7.36(t,J=7.5Hz,2H),7.28(m,1H),7.21(m, 2H),7.11(d,J=8.2Hz,2H),6.99(t,J=7.3Hz,1H),6.52(s,1H),5.37(s,1H),1.65(s,6H). 13 C{ 1H}NMR(126MHz, CDCl3)δ154.9,146.6,138.8,128.9,128.7,127.0,125.2,123.0,119.9,55.2,30.1.[M+H] + Calcdfor C 16 H 18 N2O 255.1942; Found 255.1942.

[0058] The prepared white solid product is 1-phenyl-3-(2-phenylpropan-2-yl)urea, and its structural formula is:

[0059]

[0060] In Example 1-6, the molar ratio of aniline to 2-phenyl-2-propylamine is M. The values ​​of M and P are shown in Table 1.

[0061] The yield and selectivity of 1-phenyl-3-(2-phenylpropan-2-yl)urea prepared in Examples 1-6 are shown in Table 1.

[0062] Table 1

[0063]

[0064] In Table 1, P = 0.5 MPa corresponds to an amount of COS of 3-6 mmol, and a molar ratio of COS to 2-phenyl-2-propylamine of 3-6:1.

[0065] The yield refers to the isolated yield of 1-phenyl-3-(2-phenylpropan-2-yl)urea calculated based on 2-phenyl-2-propylamine; yield = (actual yield / theoretical yield)*100%.

[0066] Selectivity = (amount of substrate consumed by target product / total consumption of substrate)*100%.

[0067] Example 7

[0068] 1 mmol of 2-phenyl-2-propylamine and 2 mmol of p-methylaniline were used as reaction substrates, and the preparation method of Example 1 was used to obtain a crude product; wherein P = 0.5 Mpa. The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether: ethyl acetate (V / V) = 20 / 1-2 / 1 was used as a developing solvent to purify the crude product, and 243 mg of a white solid product was obtained.

[0069] The prepared white solid product mp = 100-102 ° C; 1H NMR (500MHz, CDCl3) δ7.31(m,6H),7.21(m,7H),7.06(d,J=5.9Hz,2H),4.43(m,5H),3.52(t,J=6.3Hz,2H),2.77(d,J=6.6Hz,2H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ158.5,139.3,137.7,128.9,128.8,128.6,127.5,127.3,126.3,50.4,42.2,36.4.[M+H] + Calcd for C 23 H 24 N2O 345.1961; Found 345.1962.

[0070] The prepared white solid product is 1-(2-phenylpropan-2-yl)-3-(p-tolyl)urea (1-(2-phenylpropan-2-yl)-3-(p-tolyl)urea), and its structural formula is:

[0071]

[0072] According to calculation, the yield of 1-(2-phenylpropan-2-yl)-3-(p-tolyl)urea was 91% and the selectivity was 95%.

[0073] Example 8

[0074] The reaction was scaled up to gram scale in a 100 mL mechanically stirred high pressure reactor.

[0075] 2-phenylpropan-2-amine (10mmol, 1.36g), p-methylaniline (20mmol, 2.15g) and 30mL acetonitrile (MeCN) were loaded into a 100mL mechanical stirring high pressure reactor (hereinafter referred to as reactor). The reactor was flushed with N2 to remove air, and then COS was loaded to make the reactor pressure reach 0.5MPa (the amount of COS was about 50mmol). The reactor was stirred at 25°C for 4 hours, and then heated and stirred at 70°C for 8 hours.

[0076] After the reaction is completed, dichloromethane (20mL) is added to the mixture in the reactor, filtered, and the filtrate is rinsed with 10mL dichloromethane to obtain a partially asymmetric urea pure product (0.56g); the filtrate is concentrated by rotary evaporation, and the concentrated filtrate is added with 0.5mol / LHCl aqueous solution to neutralize the amine in the reaction system to remove any residual amine, extracted three times with ethyl acetate (EtOAc), and the combined organic layer is dried with anhydrous MgSO4, filtered, and the filtrate is decompressed to remove EtOAc. Further purified by silica gel column chromatography (PE / EA=20 / 1 to 1 / 1) to obtain the product 1-(2-phenylpropan-2-yl)-3-(p-tolyl)urea (1.72g) (methoxythiazol).

[0077] According to calculation, the yield of 1-(2-phenylpropan-2-yl)-3-(p-tolyl)urea was 85% and the selectivity was 87%.

[0078] Example 9

[0079] Using 1 mmol cyclohexylamine and 2 mmol aniline as reaction substrates, the preparation method of Example 6 was adopted to obtain a crude product, wherein M=2, P=0.5 MPa.

[0080] The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether:ethyl acetate (V / V) = 10 / 1-2 / 1 was used as the developing solvent to purify the crude product to obtain 201 mg of a white solid product.

[0081] The prepared white solid product mp = 177-180 ° C; 1 H NMR(500MHz, CDCl3)δ7.29(m,4H),7.08(t,J=6.3Hz,1H),6.57(s,1H),4.85(m,1H),3.76-3.56(m,1H ),1.96(d,J=10.1Hz,2H),1.69(d,J=13.5Hz,2H),1.60(d,J=10.4Hz,1H),1.36(m,2H),1.13(m,3H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ155.1,138.7,129.3,123.7,121.0,49.0,33.7,25.5,24.9.[M+H] + Calcdfor C 13 H 18 N2O 219.1492; Found 219.1492.

[0082] The prepared white solid product is 1-cyclohexyl-3-phenylurea, and its structural formula is:

[0083] The yield of 1-cyclohexyl-3-phenylurea was calculated to be 92% and the selectivity was 95%.

[0084] Example 10

[0085] Using 1 mmol tert-butylamine and 2 mmol aniline as reaction substrates, the preparation method of Example 6 was adopted to obtain a crude product, wherein M=2, P=0.5 MPa.

[0086] The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether:ethyl acetate (V / V) = 10 / 1-2 / 1 was used as the developing solvent to purify the crude product to obtain 169 mg of a white solid product.

[0087] The prepared white solid product mp = 163-165 ° C; 1 H NMR (500MHz, CDCl3) δ7.27(m,4H),7.03(m,1H),6.63(s,1H),4.92(s,1H),1.36(s,9H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ155.1,139.01,129.2,123.32,120.6,50.76,29.36.[M+H] + Calcd for C 11 H 16 N2O 193.1335; Found 193.1336.

[0088] The prepared white solid product is 1-(tert-butyl)-3-phenylurea, and its structural formula is:

[0089] The yield of 1-(tert-butyl)-3-phenylurea was calculated to be 88% and the selectivity was 90%.

[0090] Comparative Example 1

[0091] 1mmol isopropylamine and 2mmol aniline were used as reaction substrates. The reaction substrate and acetonitrile (MeCN) (2mL) were loaded into a 15mL stainless steel autoclave equipped with a magnetic stirrer; N2 was blown into the stainless steel autoclave to remove the air in the stainless steel autoclave. Subsequently, COS was introduced into the stainless steel autoclave to make the pressure of COS in the stainless steel autoclave 0.5Mpa. The stainless steel autoclave was placed in a 25°C constant temperature sand bath, reacted for 4 hours under stirring conditions, and then heated to 70°C and continued to react for 8 hours under stirring conditions.

[0092] After the reaction is completed, 0.5 mol / L of dilute hydrochloric acid aqueous solution is added to the reaction mixture solution to neutralize the unreacted amine in the reaction system until the reaction solution is neutral, and then extracted with ethyl acetate three times. The organic layers are combined, dried over anhydrous MgSO4, filtered, and the filtrate is concentrated under reduced pressure to obtain a crude product.

[0093] The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether:ethyl acetate (V / V) = 10 / 1-2 / 1 was used as the developing solvent to purify the crude product to obtain 111 mg of a white solid product.

[0094] The prepared white solid product mp = 148-150 ° C; 1 H NMR (500MHz, CDCl3) δ7.33-7.27(m,4H),7.06(m,1H),6.75(s,1H),4.91(d,J=7.1Hz,1H),4.00(m,1H),1.16(d,J=6.5Hz,6H). 13 C{ 1 H}NMR(126MHz, CDCl3)δ155.3,138.8,129.2,123.5,120.8,42.2,23.2.[M+H] + Calcdfor C 10 H 14 N2O 179.1179; Found 179.1179.

[0095] The prepared white solid product is 1-isopropyl-3-phenylurea, and its structural formula is:

[0096] According to calculation, the yield of 1-isopropyl-3-phenylurea is 60% and the selectivity is 61%.

[0097] Comparative Example 2

[0098] 1mmol n-butylamine and 2mmol aniline were used as reaction substrates, and the preparation method of Comparative Example 1 was used to obtain a crude product; wherein, M=2, P=0.5Mpa. The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether: ethyl acetate (V / V) = 10 / 1-2 / 1 was used as a developing solvent to purify the crude product, and 106mg of a white solid product was obtained.

[0099] The prepared white solid product mp = 125-127 ° C; 1 H NMR (500MHz, DMSO-d6) δ8.35(s,1H),7.37(d,J=8.2Hz,2H),7.20(t,J=7.6Hz,2H),6.87(t,J=7 .3Hz,1H),6.08(t,J=5.1Hz,1H),3.07(m,2H),1.41(m,2H),1.31(m,2H),0.89(t,J=7.2Hz,3H). 13 C{ 1 H}NMR(126MHz,DMSO-d6)δ155.6,141.1,129.1,121.3,118.0,39.1,32.3,20.0,14.2.[M+H] + Calcd for C 11 H 16 N2O 193.1335; Found 193.1336.

[0100] The prepared white solid product is 1-butyl-3-phenylurea, and its structural formula is:

[0101] The yield of 1-butyl-3-phenylurea was calculated to be 55% and the selectivity was 56%.

[0102] Comparative Example 3

[0103] 1 mmol benzylamine and 3 mmol n-butylamine were used as reaction substrates, and the preparation method of Comparative Example 1 was used to obtain a crude product; wherein M=2, P=0.5 Mpa. The crude product was separated by wet column chromatography (200 mesh silica gel): petroleum ether: ethyl acetate (V / V) = 10 / 1-2 / 1 was used as a developing solvent to purify the crude product, and 136 mg of a white solid product was obtained.

[0104] The prepared white solid product mp = 70-74 ° C; 1H NMR (500MHz, DMSO-d6) δ7.30(t,J=7.4Hz,2H),7.22(m,3H),6.25(t,J=5.7Hz,1H),5.88(t,J= 5.5Hz,1H),4.32-4.05(m,2H),3.00(m,2H),1.35(m,2H),1.26(m,2H),0.87(t,J=7.3Hz,3H). 13 C{ 1 H}NMR(126MHz,DMSO-d6)δ158.5,141.5,128.6,127.4,127.0,43.3,39.5,32.6,20.0,14.2.[M+H] + Calcd for C 12 H 18 N2O 207.1492; Found 207.1492.

[0105] The prepared white solid product is 1-benzyl-3-butylurea, and its structural formula is:

[0106] According to calculation, the yield of 1-benzyl-3-butylurea is 60% and the selectivity is 61%.

[0107] The yield of comparative examples 1-3 is 55-60% and the selectivity is 55-61%. Example 6 uses 2-phenyl-2-propylamine and aniline as reaction substrates, and its yield is 90% and selectivity is 91%. The difference between Example 6 and comparative examples 1-3 is only that the substrates are different; relative to comparative examples 1-3, the yield of Example 6 is increased by 30-45% and the selectivity is increased by 30-36%. It can be concluded that the choice of substrate significantly increases the yield and selectivity of the target product N, N'-disubstituted asymmetric urea. That is, compared with the existing method of asymmetric urea, the synthesis method of the present invention significantly increases the yield and selectivity of the target product N, N'-disubstituted asymmetric urea; the method of the present invention has significant progress.

Claims

1. A method for synthesizing N,N'-disubstituted asymmetric urea, characterized in that: The synthesis method comprises: a primary amine compound I and a primary amine compound II are subjected to a two-stage reaction using carbonyl sulfide as a carbonylation reagent; the temperature of the second-stage reaction is higher than the temperature of the first-stage reaction; The primary amine compound I is a fatty primary amine with steric hindrance at the α position; the α position of the fatty primary amine refers to the position of the first carbon atom connected to the amino group; The primary amine compound II is an aromatic primary amine.

2. The synthesis method according to claim 1, characterized in that The α-position hindered fatty primary amine is selected from 2-phenyl-2-propylamine, cyclohexylamine, tert-butylamine; or / and, The aromatic primary amine is selected from aniline and p-methylaniline.

3. The synthesis method according to claim 1, characterized in that The molar ratio of the primary amine compound I to the primary amine compound II is 1:1.5-3, preferably 1:2-3; or / and, The molar ratio of the carbonyl sulfide to the primary amine compound I is 2-6:1, preferably 3-6:

1.

4. The synthesis method according to claim 1, characterized in that The first stage reaction temperature is 20°C-35°C; or / and, The first stage reaction time is 2h-8h; or / and, The reaction temperature in the second stage is 60-90°C; or / and, The second stage reaction time is 6h-24h.

5. The synthesis method according to claim 1, characterized in that The reaction is carried out in the absence of a catalyst; or / and, The reaction is carried out in a solvent-free or polar aprotic solvent; or / and, The reaction is carried out under air-tight conditions.

6. The synthesis method according to claim 5, characterized in that The polar aprotic solvent is selected from at least one of acetonitrile, N-methylpyrrolidone and N,N-dimethylformamide.

7. The synthesis method according to claim 1, characterized in that After the reaction is completed, recrystallization or column chromatography separation is performed; The recrystallization comprises: adding a solvent for crystallization and filtering, and the obtained crystal is the N,N'-disubstituted asymmetric urea; The column chromatography separation comprises: neutralizing with an acidic solution, extracting with an extractant, drying the organic layer with a neutral drying agent, filtering, concentrating the filtrate under reduced pressure to obtain a crude product, and purifying the crude product by silica gel column chromatography to obtain the N,N'-disubstituted asymmetric urea.

8. The synthesis method according to claim 7, characterized in that The filtrate obtained by filtering during the recrystallization is subjected to the column chromatography separation.

9. The synthesis method according to claim 7 or 8, characterized in that: The extractant is selected from one or more of ethyl acetate and dichloromethane; or / and, The solvent is selected from one or more of ethyl acetate and dichloromethane; or / and, The acidic solution is selected from one or more of hydrochloric acid, sulfuric acid, nitric acid, acetic acid and perchloric acid; or / and, The neutral desiccant is selected from at least one of anhydrous magnesium sulfate, anhydrous calcium chloride, anhydrous copper sulfate, anhydrous calcium sulfate, anhydrous sodium sulfate, and aluminum oxide.

10. A method for synthesizing cypermethrin, characterized in that: The synthesis method according to any one of claims 1 to 9 is adopted, wherein the primary amine compound I is 2-phenyl-2-propylamine, and the primary amine compound II is p-methylaniline.

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