A method for preparing an n-phenylphenylenediamine compound by structural reorganization of an imidazole compound

Abstract

The application relates to the technical field of organic synthesis, in particular to a method for preparing N-phenylphenylenediamine compounds by structure reorganization of imidazole compounds. The method for preparing N-phenylphenylenediamine compounds by structure reorganization of imidazole compounds provided by the application uses a borane compound as a reducing agent, reduces the imidazole compound to generate a boron-nitrogen heterocyclic compound, and then further ring-opening and oxidizing the boron-nitrogen heterocyclic compound by sodium borate tetrahydrate to generate the N-phenylphenylenediamine compound; the reaction process has few by-products, the selectivity of the N-phenylphenylenediamine compound is high, the yield is high, and subsequent separation and purification is simple. Moreover, the method provided by the application is simple in process, green and environment-friendly, simple in operation, low in cost, high in safety, and suitable for industrialized production.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of organic synthesis, in particular to a method for preparing N-phenylphenylenediamine compounds by structural reorganization of imidazole compounds. BACKGROUND

[0002] Nitrogen-containing heterocyclic compounds are widely present in natural products, pesticide chemicals and medicinal chemicals with biological activity, and chemists have been committed to the modification and derivation of the structures of the heterocyclic compounds for synthesizing organic compounds with higher value. For example, the structural modification of a drug molecule containing a nitrogen-containing heterocyclic ring can improve the drug activity and reduce the toxicity. Most of the reported modifications are external modifications of the nitrogen-containing heterocyclic compounds, and there are few reports on the changes of the core skeletons of the nitrogen-containing heterocyclic compounds.

[0003] N-phenylphenylenediamine compounds have potential drug activity and synthetic application, and the synthesis thereof generally needs to be obtained by step-by-step protection of aniline compounds, and the total yield of the product is low. SUMMARY

[0004] Therefore, the purpose of the application is to provide a method for preparing N-phenylphenylenediamine compounds by structural reorganization of imidazole compounds, and the method provided by the application has high yield and high selectivity of N-phenylphenylenediamine compounds.

[0005] In order to achieve the above-mentioned application purposes, the application provides the following technical scheme:

[0006] The application provides a method for preparing N-phenylphenylenediamine compounds by structural reorganization of imidazole compounds, comprising the following steps:

[0007] The imidazole compound and the borane compound are mixed to perform a reduction reaction in a protective atmosphere to obtain a boron-nitrogen heterocyclic compound;

[0008] The boron-nitrogen heterocyclic compound is mixed with sodium perborate tetrahydrate to perform an open ring oxidation reaction to obtain the N-phenylphenylenediamine compound.

[0009] Preferably, the imidazole compound has the structure shown in formula 1.

[0010]

[0011] In formula 1, R 1 The phenyl, substituted aryl, naphthyl, benzodioxazolyl or 1,2-methylenedioxyphenyl; R 2 The hydrogen, methyl, methoxy and halogen.

[0012] Preferably, the substituent in the substituted aryl group comprises one or more of methyl, tert-butyl, methoxy, oxyphenyl, thiomethyl and fluorine.

[0013] Preferably, the borane compound is used in the form of a tetrahydrofuran solution of the borane compound, and the concentration of the tetrahydrofuran solution of the borane compound is 2 mol / L.

[0014] Preferably, the borane compound comprises a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex.

[0015] Preferably, the molar ratio of the imidazole compound to the borane compound is 1:3-5.

[0016] Preferably, the temperature of the reduction reaction is 80-100℃, and the time is 12-24h.

[0017] Preferably, the molar ratio of the boron-nitrogen heterocyclic compound to the sodium perborate tetrahydrate is 1:3-5.

[0018] Preferably, the temperature of the ring-opening oxidation reaction is 30-40℃, and the time is 4-6h.

[0019] The method for preparing N-phenylphenylenediamine compounds by structural reorganization of imidazole compounds provided by the present application uses a borane compound as a reducing agent, boronizes and reduces the imidazole compound to generate a boron-nitrogen heterocyclic compound, and further ring-opening oxidizes the boron-nitrogen heterocyclic compound by sodium perborate tetrahydrate to generate the N-phenylphenylenediamine compound. The reaction process has few by-products, the selectivity of the N-phenylphenylenediamine compound is high, the yield is high, and the subsequent separation and purification is simple. Moreover, the method provided by the present application has the advantages of simple process, green environmental protection, simple operation, low cost, high safety, and suitability for industrial production. DETAILED DESCRIPTION

[0020] The present application provides a method for preparing N-phenylphenylenediamine compounds by structural reorganization of imidazole compounds, characterized by comprising the following steps:

[0021] Mixing the imidazole compound and the borane compound, and performing a reduction reaction in a protective atmosphere to obtain a boron-nitrogen heterocyclic compound.

[0022] Mixing the boron-nitrogen heterocyclic compound and sodium perborate tetrahydrate, and performing a ring-opening oxidation reaction to obtain an N-phenylphenylenediamine compound.

[0023] Unless otherwise specified, the raw materials used in the present application are all commercially available.

[0024] Mixing the imidazole compound and the borane compound, and performing a reduction reaction in a protective atmosphere to obtain a boron-nitrogen heterocyclic compound.

[0025] In the present application, the imidazole compound preferably has a structure represented by Formula 1:

[0026]

[0027] In Formula 1, R 1 Preferably, the phenyl group includes a phenyl group, the substituted aryl group includes a phenyl group, and the substituent of the substituted aryl group includes one or more of a methyl group, a tert-butyl group, a methoxy group, an oxyphenyl group, a thiomethyl group, and a fluorine group. Preferably, R 2 Preferably, the substituent includes one or more of hydrogen, a methyl group, a methoxy group, and a halogen. Preferably, the halogen includes fluorine, chlorine, or bromine. When the substituent is two or more of the above substituents, the present application does not have a special limitation on the substitution position of the different types of substituents.

[0028] In the present application, the imidazole compound preferably includes 1-phenyl-1H-benzo[d]imidazole, 1-(4-(tert-butyl)phenyl)-1H-benzo[d]imidazole, 1-(4-methoxyphenyl)-1H-benzo[d]imidazole, 1-(4-phenoxyphenyl)-1H-benzo[d]imidazole, 1-(4-(methylthio)phenyl)-1H-benzo[d]imidazole, 1-(4-fluorophenyl)-1H-benzo[d]imidazole, 1-(2-naphthyl)-1H-benzo[d]imidazole, 1-(1,2-methylenedioxyphenyl)-1H-benzo[d]imidazole, 5,6-dimethyl-1-phenyl-1H-benzo[d]imidazole, 5,6-dimethoxy-1-phenyl-1H-benzo[d]imidazole, 5,6-difluoro-1-phenyl-1H-benzo[d]imidazole, 5,6-dichloro-1-phenyl-1H-benzo[d]imidazole, 5,6-dibromo-1-phenyl-1H-benzo[d]imidazole, 6-chloro-4-methyl-1-phenyl-1H-benzo[d]imidazole, or 1-benzyl-1H-benzo[d]imidazole.

[0029] In the present application, the borane compound is preferably used in the form of a tetrahydrofuran solution of the borane compound, and the concentration of the tetrahydrofuran solution of the borane compound is preferably 2 mol / L. In the present application, the borane compound preferably includes a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex.

[0030] In the present application, the molar ratio of the imidazole compound to the borane compound is preferably 1:3 to 5, more preferably 1:3.5 to 4.5, and further preferably 1:4.

[0031] The mixing method is not particularly limited in the present application, and the raw materials can be mixed uniformly using a mixing method well known to those skilled in the art, such as stirring.

[0032] In the present application, the temperature of the reduction reaction is preferably 80-100℃, more preferably 90-100℃; the time of the reduction reaction is preferably 12-24h, more preferably 12-15h. In the present application, the protective atmosphere preferably comprises nitrogen, argon or helium; the pressure of the protective atmosphere is preferably 1atm.

[0033] In the present application, the boron-nitrogen heterocyclic compound preferably has the structure shown in Formula 2:

[0034]

[0035] R 1 and R 2 in Formula 2 are preferably the same as R 1 and R 2 in Formula 1, which are not repeated here.

[0036] In the present application, the reaction formula of the reduction reaction is as follows:

[0037]

[0038] After the reduction reaction, the present application preferably further comprises cooling the obtained reduction reaction solution to room temperature, and then performing a subsequent ring-opening oxidation reaction.

[0039] After obtaining the boron-nitrogen heterocyclic compound, the present application mixes the boron-nitrogen heterocyclic compound with sodium perborate tetrahydrate to perform a ring-opening oxidation reaction, thereby obtaining an N-phenylphenylenediamine compound.

[0040] In the present application, the molar ratio of the boron-nitrogen heterocyclic compound to sodium perborate tetrahydrate is preferably 1:3-5, more preferably 1:4-5.

[0041] The mixing in the present application is not particularly limited, and the raw materials can be mixed uniformly by using a mixing method well known to those skilled in the art, such as stirring mixing.

[0042] In the present application, the temperature of the ring-opening oxidation reaction is preferably 30-40℃, more preferably 35-40℃, and the time of the ring-opening oxidation reaction is preferably 4-6h, more preferably 4-5h. In the present application, the solvent used in the ring-opening oxidation reaction preferably comprises a tetrahydrofuran aqueous solution, and the volume ratio of tetrahydrofuran to water in the tetrahydrofuran aqueous solution is preferably 1:1-1.2, more preferably 1:1; the ratio of the amount of substance of the boron-nitrogen heterocyclic compound to the volume of the solvent is preferably 1mmol:5-20mL, more preferably 1mmol:10-15mL.

[0043] After the ring-opening oxidation reaction, the application preferably further comprises purifying the obtained ring-opening oxidation reaction solution by silica gel column chromatography after cooling to room temperature, and concentrating the obtained eluent to constant weight to obtain the N-phenylphenylenediamine compound. In the application, the eluent used in the silica gel column chromatography is preferably a petroleum ether-ethyl acetate mixed solvent, and the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is preferably 1:1 to 10:1, more preferably 2:1 to 8:1, and further preferably 4:1 to 5:1. The application does not have any special limitation on the concentration, and any concentration method known to those skilled in the art can be used, such as rotary evaporation under reduced pressure.

[0044] In the application, the N-phenylphenylenediamine compound has the structure shown in Formula 3:

[0045]

[0046] R 1 and R 2 are preferably the same as R 1 and R 2 in Formula 1, which will not be described here again.

[0047] In the application, the reaction formula of the ring-opening oxidation reaction is as follows:

[0048]

[0049] The technical solutions in the application will be described clearly and completely in combination with the embodiments in the application. Obviously, the described embodiments are only some of the embodiments of the application, but not all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0050] In the following embodiments, all imidazole compounds are prepared according to the published literature (Tetrahedron 2011, 67, 5282-5288.), and other raw materials are commercially available products known to those skilled in the art.

[0051] Example 1

[0052]

[0053] A 10 mL pressure-resistant reaction tube was added with 1-phenyl-1H-benzo[d]imidazole (denoted as 1a, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) respectively, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h. After the reaction temperature was reduced to room temperature, the product system containing compound 3a was obtained. Then, the product system was purified by silica gel column chromatography, and a mixed solvent of petroleum ether: ethyl acetate (volume ratio 4:1) was used as the eluent for elution. The obtained eluent was rotary evaporated under reduced pressure to obtain compound 3a (N 1 -methyl-N 2 -phenyl-1,2-diamine, with a yield of 88%.

[0054] The characterization data of compound 3a are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.21-7.06 (m, 4H), 6.80 (t, J = 7.3 Hz, 1H), 6.73-6.62 (m, 4H), 5.04 (s, 1H), 4.14 (s, 1H), 2.82 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 145.9, 145.4, 129.4, 128.0, 126.5, 125.0, 119.3, 117.1, 115.2, 110.6, 30.7.

[0055] Example 2

[0056]

[0057] A 10 mL pressure-resistant reaction tube was added with 1-phenyl-1H-benzo[d]imidazole (denoted as 1a, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) respectively, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h. After the reaction temperature was reduced to room temperature, the product system containing compound 3a was obtained. Then, the product system was purified by silica gel column chromatography, and a mixed solvent of petroleum ether: ethyl acetate (volume ratio 4:1) was used as the eluent for elution. The obtained eluent was rotary evaporated under reduced pressure to obtain compound 3a (N 1 -(4-(tert-butyl)phenyl)-N 2 -methylphenyl-1,2-diamine, with a yield of 96%.

[0058] The characterization data of compound 3b are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.25-7.15 (m, 2H), 7.16-7.05 (m, 2H), 6.77-6.55 (m, 4H), 4.99 (s, 1H), 4.15 (s, 1H), 2.82 (s, 3H), 1.28 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 145.2, 143.3, 142.2, 128.7, 126.2, 126.0, 124.4, 117.2, 115.1, 110.5, 34.1, 31.7, 30.7.

[0059] Example 3

[0060]

[0061] A 10 mL pressure-resistant reaction tube was added with 1-(4-methoxyphenyl)-1H- benzo[d]imidazole (denoted as 1c, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3c. Then the reaction temperature was reduced to room temperature, and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as the eluent. The obtained eluent was rotary evaporated under reduced pressure to obtain compound 3c (N 1 -4-methoxyphenyl)-N 2 - methylbenzene-1,2-diamine, with a yield of 88%.

[0062] The characterization data of compound 3c are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.07 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 6.79 (d, J = 8.9 Hz, 2H), 6.69 (dd, J = 12.3, 8.6 Hz, 4H), 4.88 (s, 1H), 4.07 (s, 1H), 3.75 (s, 3H), 2.84 (s, 3H). 13CNMR(101MHz,Chloroform-d)δ153.8,144.2,139.0,130.2,125.2,122.6,117.9,117.4,114.9,110.6,55.8,30.8.

[0063] Example 4

[0064]

[0065] A solution of 1-(4-phenoxyphenyl)-1H-benzo[d]imidazole (denoted as 1d, 0.2 mmol) and a tetrahydrofuran solution of a boron dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration 2 mol / L) was added to a 10 mL pressure-resistant reaction tube. The mixture was stirred at 100 °C for 12 h under an argon atmosphere (1 atm). After the reaction was complete, the temperature was lowered to room temperature, and 1 mmol of sodium perborate tetrahydrate and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added. The mixture was stirred at 40 °C for 4 h to obtain a product system containing compound 3d. The product was then purified by silica gel column chromatography after the reaction temperature was lowered to room temperature, using a petroleum ether:ethyl acetate mixture (volume ratio 4:1) as the eluent. The eluent was evaporated to dryness under reduced pressure to obtain compound 3d (N... 1 -Methyl-N 2 -(4-phenoxyphenyl)benzene-1,2-diamine, yield 98%.

[0066] The characterization data for compound 3d are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.27(t,J=7.9Hz,2H),7.17-7.05(m,2H),7.01(t,J=7.4Hz,1H),6.95( d,J=7.9Hz,2H),6.89(d,J=8.8Hz,2H),6.69(t,J=8.6Hz,4H),4.99(s,1H),4.10(s,1H),2.84(s,3H). 13 C NMR (101MHz, Chloroform-d) δ158.7,149.5,144.9,142.0,129.7,128.8,126.1,124.1,122.4,121.0,117.6,117.3,116.8,110.7,30.7.

[0067] Example 5

[0068]

[0069] A 10 mL pressure-resistant reaction tube was added with 1-(4-(methylthio)phenyl)-1H- benzo[d]imidazole (denoted as 1e, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3e. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as the eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3e (N 1 -methyl-N 2 -(4-(methylthio)phenyl)benzene-1,2-diamine with a yield of 59%.

[0070] The characterization data of compound 3e are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.22-7.17 (m, 2H), 7.14 (td, J = 7.7, 1.5 Hz, 1H), 7.08 (dd, J = 7.6, 1.5 Hz, 1H), 6.69 (td, J = 10.0, 8.7, 1.7 Hz, 2H), 6.66-6.59 (m, 2H), 5.07 (s, 1H), 4.11 (s, 1H), 2.83 (s, 3H), 2.42 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 145.3, 144.5, 130.8, 127.8, 126.6, 125.0, 117.2, 115.9, 110.6, 30.7, 18.7.

[0071] Example 6

[0072]

[0073] A 10 mL pressure-resistant reaction tube was charged with 1-(4-fluorophenyl)-1H- benz[d]imidazole (denoted as 1f, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L), and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was lowered to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3f. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as eluent, and the obtained eluate was rotary evaporated under reduced pressure to obtain compound 3f (N 1 -1-(4-Fluorophenyl)-1H-benz[d]imidazole 2 -1-(4-Fluorophenyl)-1H-benz[d]imidazole

[0074] The characterization data of compound 3f are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.20 (t, J = 7.9 Hz, 2H), 6.94 (dd, J = 11.0, 8.2 Hz, 1H), 6.84 (t, J = 7.3 Hz, 1H), 6.67 (d, J = 7.9 Hz, 2H), 6.45 (dd, J = 12.6, 7.7 Hz, 1H), 4.92 (s, 1H), 4.10 (s, 1H), 2.78 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 150.1 (d, J = 12.9 Hz), 147.7 (d, J = 12.9 Hz), 145.4, 142.9 (d, J = 13.7 Hz), 142.6 (dd, J = 8.5, 1.4 Hz), 140.6 (d, J = 13.5 Hz), 129.6, 123.2 (dd, J = 6.6, 3.0 Hz), 119.9, 115.2, 114.2 (d, J = 1.0 Hz), 114.0 (d, J = 1.8 Hz), 99.2 (d, J = 22.1 Hz), 30.9. 19 F NMR (376 MHz, Chloroform-d) δ -125.43 (tt, J = 8.7, 4.6 Hz).

[0075] Example 7

[0076]

[0077] A 10 mL pressure-resistant reaction tube was charged with 1-(2-naphthyl)-1H- benz[d]imidazole (denoted as 1g, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L), and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was lowered to room temperature, and a mixture of sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3g. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as eluent, and the obtained eluate was rotary evaporated under reduced pressure to obtain compound 3g (N 1 -methyl-N 2 -(naphthalen-2-yl)benzene-1,2-diamine, yield of 81%.

[0078] The characterization data of compound 3g are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.68 (t, J = 7.8 Hz, 2H), 7.54 (d, J = 8.2 Hz, 1H), 7.33 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.27-7.10 (m, 3H), 7.00 (dd, J = 8.8, 2.4 Hz, 1H), 6.86 (d, J = 2.3 Hz, 1H), 6.78-6.67 (m, 2H), 5.21 (s, 1H), 4.16 (s, 1H), 2.82 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 145.5, 143.6, 135.0, 129.3, 128.6, 127.9, 127.9, 126.8, 126.6, 126.4, 125.3, 123.0, 118.6, 117.3, 110.8, 108.6, 30.8.

[0079] Example 8

[0080]

[0081] A 10 mL pressure-resistant reaction tube was added with 1-(1,2-methylenedioxyphenyl)-1H-benzo[d]imidazole (denoted as 1h, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were mixed, and stirred at 40 °C for 4 h to obtain a product system containing compound 3h. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as the eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3h (N 1 -(1,2-methylenedioxyphenyl)-N 2 -methylbenzene-1,2-diamine with a yield of 93%.

[0082] The characterization data of compound 3h are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.09 (t, J = 7.7 Hz, 1H), 7.03 (d, J = 7.5 Hz, 1H), 6.67 (dd, J = 14.1, 7.9 Hz, 3H), 6.33 (d, J = 2.1 Hz, 1H), 6.16 (dd, J = 8.3, 2.1 Hz, 1H), 5.86 (s, 2H), 4.89 (s, 1H), 4.09 (s, 1H), 2.83 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 148.4, 144.6, 141.3, 140.8, 129.5, 125.7, 123.5, 117.3, 110.6, 108.7, 108.2, 100.9, 98.9, 30.7.

[0083] Example 9

[0084]

[0085] 5,6-Dimethyl-1-phenyl-1H-benzo[d]imidazole (denoted as 1i, 0.2 mmol) and a tetrahydrofuran solution of the boron dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration 2 mol / L) were added to 10 mL pressure-resistant reaction tubes, respectively. The mixture was stirred at 100 °C for 12 h under an argon atmosphere (1 atm). After the reaction was completed, the temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added. The mixture was stirred at 40 °C for 4 h to obtain a product system containing compound 3i. The product was then purified by silica gel column chromatography after the reaction temperature was lowered to room temperature, using a petroleum ether:ethyl acetate mixture (volume ratio 4:1) as the eluent. The eluent was evaporated to dryness under reduced pressure to obtain compound 3i (N... 1 ,4,5-Trimethyl-N 2 -Benzene-1,2-diamine, yield 77%.

[0086] The characterization data for compound 3i are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.16(t,J=7.9Hz,2H),6.87(s,1H),6.76(t,J=7.3Hz,1H),6.64( d,J=7.8Hz,2H),6.52(s,1H),4.98(s,1H),3.97(s,1H),2.80(s,3H),2.25(s,3H),2.13(s,3H). 13 C NMR (101MHz, Chloroform-d) δ146.5,143.7,134.7,129.4,127.0,125.3,124.9,118.8,114.7,112.5,31.0,20.0,18.8.

[0087] Example 10

[0088]

[0089] 5,6-dimethoxy-1-phenyl-1H-benzo[d]imidazole (denoted as 1j, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) were added into 10 mL pressure-resistant reaction tubes, respectively, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3j. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as the eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3j (4,5-dimethoxy-N 1 -methyl-N 2 -phenyl-1,2-diamine, with a yield of 76%.

[0090] The characterization data of compound 3j are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.18 (t, J = 7.8 Hz, 2H), 6.81-6.71 (m, 2H), 6.62 (d, J = 7.9 Hz, 2H), 6.35 (s, 1H), 4.97 (s, 1H), 4.00 (s, 1H), 3.92 (s, 3H), 3.75 (s, 3H), 2.83 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 148.6, 146.9, 141.3, 140.5, 129.5, 118.9, 118.7, 114.2, 112.6, 96.6, 57.0, 56.3, 31.4.

[0091] Example 11

[0092]

[0093] To a 10 mL pressure-resistant reaction tube, 5,6-difluoro-1-phenyl-1H-benzo[d]imidazole (denoted as 1k, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) were added respectively, and stirred at 100 °C under argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3k. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as eluent. The obtained eluent was rotary evaporated under reduced pressure to obtain compound 3k (4,5-difluoro-N 1 -methyl-N 2 -phenyl-1,2-diamine with a yield of 98%.

[0094] The characterization data of compound 3k are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.20 (t, J = 7.9 Hz, 2H), 6.94 (dd, J = 11.0, 8.3 Hz, 1H), 6.84 (t, J = 7.4 Hz, 1H), 6.66 (d, J = 7.7 Hz, 2H), 6.45 (dd, J = 12.7, 7.7 Hz, 1H), 4.92 (s, 1H), 4.09 (s, 1H), 2.78 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 150.1 (d, J = 13.0 Hz), 147.6 (d, J = 12.9 Hz), 145.4, 142.9 (d, J = 13.5 Hz), 142.6 (dd, J = 8.5, 1.6 Hz), 140.6 (d, J = 13.6 Hz), 129.6, 123.2 (dd, J = 6.6, 3.0 Hz), 119.9, 115.2, 114.1 (dd, J = 18.5, 1.8 Hz), 99.1 (d, J = 22.1 Hz), 30.8. 19 F NMR (376 MHz, Chloroform-d) δ -140.53 (ddd, J = 22.1, 12.6, 8.2 Hz), -152.66 (ddd, J = 22.9, 11.0, 7.6 Hz).

[0095] Example 12

[0096]

[0097] A 10 mL pressure-resistant reaction tube was added with 5,6-dichloro-1-phenyl-1H- benzo[d]imidazole (denoted as 1l, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3l. Then the reaction temperature was reduced to room temperature, and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as an eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3l (4,5-dichloro-N 1 -methyl-N 2 -phen-1,2-diamine, with a yield of 86%.

[0098] The characterization data of compound 3l are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.27-7.16 (m, 2H), 7.14 (s, 1H), 6.87 (t, J = 7.4 Hz, 1H), 6.70 (d, J = 6.6 Hz, 3H), 4.97 (s, 1H), 4.16 (s, 1H), 2.81 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 144.6, 144.5, 129.6, 129.2, 128.1, 125.4, 120.4, 119.1, 115.8, 111.6, 30.6.

[0099] Example 13

[0100]

[0101] A 10 mL pressure-resistant reaction tube was added with 5,6-dichloro-1-phenyl-1H- benzo[d]imidazole (denoted as 1l, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration of 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40 °C for 4 h to obtain a product system containing compound 3l. Then the reaction temperature was reduced to room temperature, and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as an eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3l (4,5-dichloro-N1 - methyl-N 2 - phen-1,2-diamine with a yield of 58%.

[0102] The characterization data of compound 3m are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.28 (s, 1H), 7.22 (t, J = 7.9 Hz, 2H), 6.93-6.83 (m, 2H), 6.70 (d, J = 7.8 Hz, 2H), 4.97 (s, 1H), 4.17 (s, 1H), 2.80 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 145.1, 144.5, 129.6, 129.0, 128.2, 121.1, 120.4, 115.9, 114.7, 110.0, 30.5.

[0103] Example 14

[0104]

[0105] A 10 mL pressure-resistant reaction tube was added with 6-chloro-4-methyl-1-phenyl-1H-benzo[d]imidazole (denoted as 1n, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, concentration of 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100°C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was reduced to room temperature, and a mixture of sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) was added, and stirred at 40°C for 4 h to obtain a product system containing compound 3n. Then the reaction temperature was reduced to room temperature, and purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether: ethyl acetate = 4:1 (volume ratio) as an eluent. The obtained eluate was rotary evaporated under reduced pressure to obtain compound 3n (5-chloro-N 2 ,3-dimethyl-N 1 - phen-1,2-diamine with a yield of 87%.

[0106] The characterization data of compound 3n are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.29 (t, J = 7.8 Hz, 2H), 7.13-7.01 (m, 3H), 6.95 (t, J = 7.4 Hz, 1H), 6.70 (d, J = 2.0 Hz, 1H), 6.39 (s, 1H), 2.79 (s, 1H), 2.67 (s, 3H), 2.26 (s, 3H). 13C NMR (101MHz, Chloroform-d) δ142.9,138.9,136.3,132.6,129.6,128.7,122.1,121.5,118.7,113.7,34.9,17.7.

[0107] Example 15

[0108]

[0109] A solution of 1-benzyl-1H-benzo[d]imidazole (denoted as 1o, 0.2 mmol) and a tetrahydrofuran solution of a boron dimethyl sulfide complex (denoted as 2a, 0.6 mmol, concentration 2 mol / L) was added to a 10 mL pressure-resistant reaction tube. The mixture was stirred at 100 °C for 12 h under an argon atmosphere (1 atm). After the reaction was completed, the temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added and stirred at 40 °C for 4 h to obtain a product system containing compound 3o. The product system was then purified by silica gel column chromatography after the reaction temperature was lowered to room temperature, using a mixed solvent of petroleum ether:ethyl acetate (volume ratio 4:1) as the eluent. The eluent was evaporated to dryness under reduced pressure to obtain compound 3o (N 1 -Benzyl-N 2 -Methylphenyl-1,2-diamine, yield 71%.

[0110] The characterization data for compound 3o are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.43-7.31(m,4H),7.31-7.25(m,1H),6.85(td,J=7.5,1.6Hz,1H),6. 78(td,J=7.6,1.5Hz,1H),6.70(ddd,J=7.6,2.8,1.6Hz,2H),4.28(s,2H),3.42(s,2H),2.84(s,3H). 13 C NMR (101MHz, Chloroform-d) δ139.6,138.6,137.2,128.7,128.0,127.4,119.6,119.1,111.7,110.8,48.9,31.1.

[0111] Comparative Example 1

[0112] Compound 3a was prepared according to the method of Example 1, except that the borane dimethyl sulfide complex was replaced with 9-BBN. Compound 3a was not detected, and only 1a was detected in the reaction solution.

[0113] Comparative Example 2

[0114] The compound 3a was prepared according to the procedure of Example 1, except that the borane dimethylsulfide complex was replaced by HBpin. No compound 3a was detected, only 1a was detected in the reaction mixture.

[0115] The above only is the preferred embodiment of the present application, it should be pointed out that, for the ordinary skilled in the art, without departing from the principles of the present application, can also make a number of improvements and refinements, these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A method for preparing an N-phenylphenylenediamine compound by structural reorganization of an imidazole compound, comprising the following steps: mixing the imidazole compound and a borane compound, and performing a reduction reaction in a protective atmosphere to obtain a boron-nitrogen heterocyclic compound; mixing the boron-nitrogen heterocyclic compound and sodium perborate tetrahydrate, and performing an open ring oxidation reaction to obtain the N-phenylphenylenediamine compound; the reaction formula of the reduction reaction is as follows: the reaction formula of the open ring oxidation reaction is as follows: the borane compound is selected from a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex; the temperature of the reduction reaction is 80-100℃. The substituents in the substituted aryl group include one or more of a methyl group, a tert-butyl group, a methoxy group, a phenoxy group, a thiomethyl group, and fluorine. The borane compound is used in the form of a tetrahydrofuran solution of the borane compound, and the concentration of the tetrahydrofuran solution of the borane compound is 2 mol / L. The molar ratio of the imidazole compound to the borane compound is 1:3-5. ； The time of the reduction reaction is 12-24 h. ； wherein R 1 is selected from phenyl, substituted aryl, naphthyl or 1,2-methylenedioxyphenyl; R 2 is selected from one or more of hydrogen, methyl, methoxy and halogen; The molar ratio of the boron-nitrogen heterocyclic compound to sodium perborate tetrahydrate is 1:3-5. The temperature of the open ring oxidation reaction is 30-40℃, and the time is 4-6 h.

2. The production method according to claim 1, characterized by, ​ 3. The preparation method according to claim 1, characterized in that, ​ 4. The method of claim 1, wherein, ​ 5. The method of any one of claims 1 to 4, wherein the method further comprises the step of: ​ 6. The method of claim 1, wherein, ​ 7. The production method according to claim 1 or 6, characterized by, ​

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