Method for preparing N-phenyl phenylenediamine compound through structural reforming of imidazole compound

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing an N-phenyl phenylenediamine compound through structural reforming of an imidazole compound. According to the method for preparing the N-phenyl phenylenediamine compound through structural reforming of the imidazole compound, the borane compound serves as a reducing reagent, the imidazole compound is reduced to generate a boron-nitrogen heterocyclic ring compound, then the boron-nitrogen heterocyclic ring compound is further subjected to ring-opening oxidation through sodium borate tetrahydrate to generate the N-phenyl phenylenediamine compound, and the N-phenyl phenylenediamine compound is prepared. In the reaction process, by-products are few, the N-phenylphenylenediamine compound is high in selectivity and yield, and subsequent separation and purification are simple. Moreover, the method provided by the invention is simple in process, green and environment-friendly, simple to operate, low in cost, high in safety and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing N-phenylphenylenediamine compounds by structural reforming of imidazole compounds. Background Art

[0002] Nitrogen-containing heterocyclic compounds are widely found in natural products with biological activity, pesticide chemistry and medicinal chemistry. Chemists have been committed to the modification and derivatization of heterocyclic compound structures for the synthesis of organic compounds with higher value. For example, by modifying the structure of nitrogen-containing heterocyclic drug molecules, their drug activity can be improved and their toxicity can be reduced. Most of the reports so far are external modifications of nitrogen-containing heterocyclic compounds, and there are few reports on changes to their core skeletons.

[0003] N-phenylenediamine compounds have potential pharmaceutical activity and synthetic applications. Their synthesis generally requires the stepwise protection of aniline compounds, and the overall yield of the product is low. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a method for preparing N-phenylphenylenediamine compounds by structural reforming of imidazole compounds. The method provided by the present invention has high yield and high selectivity of N-phenylphenylenediamine compounds.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

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

[0007] The imidazole compound and the borane compound are mixed and subjected to 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 and subjected to a ring-opening oxidation reaction to obtain an N-phenylphenylenediamine compound.

[0009] Preferably, the imidazole compound has a structure shown in Formula 1:

[0010]

[0011] In Formula 1, R 1 Including phenyl, substituted aryl, naphthyl, benzobisoxazolyl or 1,2-methylenedioxyphenyl; R 2 Includes one or more of hydrogen, methyl, methoxy and halogen.

[0012] Preferably, the substituents in the substituted aryl group include 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 includes borane dimethyl sulfide complex and / or borane tetrahydrofuran complex.

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

[0016] Preferably, the reduction reaction is carried out at a temperature of 80 to 100° C. and for a time of 12 to 24 hours.

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

[0018] Preferably, the ring-opening oxidation reaction is carried out at a temperature of 30 to 40° C. and for a time of 4 to 6 hours.

[0019] The method for preparing N-phenylphenylenediamine compounds by structural reforming of imidazole compounds provided by the present invention uses borane compounds as reducing agents, boronizes and reduces imidazole compounds to generate boron nitrogen heterocyclic compounds, and then further ring-opening and oxidizing with sodium borate tetrahydrate to generate N-phenylphenylenediamine compounds, and there are few by-products in the reaction process, and the selectivity and yield of N-phenylphenylenediamine compounds are high, and subsequent separation and purification are simple. Moreover, the method provided by the present invention has simple process, green and environmental protection, simple operation, low cost, high safety, and is suitable for industrial production. DETAILED DESCRIPTION

[0020] The present invention provides a method for preparing N-phenylphenylenediamine compounds by structural reforming of imidazole compounds, characterized in that it comprises the following steps:

[0021] The imidazole compound and the borane compound are mixed and subjected to reduction reaction in a protective atmosphere to obtain a boron nitrogen heterocyclic compound;

[0022] The boron nitrogen heterocyclic compound is mixed with sodium perborate tetrahydrate and subjected to a ring-opening oxidation reaction to obtain an N-phenylphenylenediamine compound.

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

[0024] The imidazole compound and the borane compound are mixed and subjected to reduction reaction in a protective atmosphere to obtain a boron nitrogen heterocyclic compound.

[0025] In the present invention, the imidazole compound preferably has a structure shown in Formula 1:

[0026]

[0027] In Formula 1, R 1 Preferably, it includes phenyl, substituted aryl, naphthyl, benzobisoxazolyl or 1,2-methylenedioxyphenyl; the aryl in the substituted aryl preferably includes phenyl, and the substituent in the substituted aryl preferably includes one or more of methyl, tert-butyl, methoxy, oxyphenyl, thiomethyl and fluorine; the R 2 Preferably, it includes one or more of hydrogen, methyl, methoxy and halogen; the halogen preferably includes fluorine, chlorine or bromine; when the substituent is two or more of the above substituents, the present invention has no special limitation on the substitution position of different types of substituents.

[0028] In the present invention, 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- 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 invention, 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 invention, the borane compound preferably includes a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex.

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

[0031] The present invention has no special limitation on the mixing. The raw materials can be evenly mixed by a mixing method well known to those skilled in the art, such as stirring and mixing.

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

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

[0034]

[0035] In Formula 2, R 1 and R 2 Preferably, R 1 and R 2 The same is not repeated here.

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

[0037]

[0038] After the reduction reaction, the present invention 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 invention mixes the boron nitrogen heterocyclic compound with sodium perborate tetrahydrate to carry out a ring-opening oxidation reaction to obtain an N-phenylphenylenediamine compound.

[0040] In the present invention, 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 present invention has no special limitation on the mixing. The raw materials can be evenly mixed by a mixing method well known to those skilled in the art, such as stirring and mixing.

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

[0043] After the ring-opening oxidation reaction, the present invention preferably further comprises cooling the obtained ring-opening oxidation reaction liquid to room temperature and purifying by silica gel column chromatography, and concentrating the obtained eluent to constant weight to obtain N-phenylphenylenediamine compounds. In the present invention, the eluent used for the silica gel column chromatography purification 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 present invention does not have any special restrictions on the concentration, and a concentration method well known to those skilled in the art can be used, such as decompression and spin drying.

[0044] In the present invention, the N-phenylenediamine compound has a structure shown in Formula 3:

[0045]

[0046] In Formula 3, R 1 and R 2 Preferably, R 1 and R 2 The same is not repeated here.

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

[0048]

[0049] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

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

[0051] Example 1

[0052]

[0053] 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) were added to a 10 mL pressure-resistant reaction tube, respectively, and stirred at 100° C. for 12 h under an argon (1 atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (tetrahydrofuran: water volume ratio of 1:1) were added, and stirred at 40° C. for 4 h. After the reaction temperature was lowered to room temperature, it was purified by silica gel column chromatography, and eluted with a mixed solvent of petroleum ether:ethyl acetate volume ratio of 4:1 as an eluent. The obtained eluate was decompressed and dried by spin drying to obtain compound 3a (N 1 -Methyl-N 2 -Benzene-1,2-diamine, yield 88%.

[0054] The characterization data of compound 3a are: 1 H NMR (400MHz, Chloroform-d) δ7.21-7.06(m,4H),6.80(t,J=7.3Hz,1H),6.73-6.62(m,4H),5.04(s,1H),4.14(s,1H),2.82(s,3H). 13 C NMR (101MHz, Chloroform-d) δ145.9,145.4,129.4,128.0,126.5,125.0,119.3,117.1,115.2,110.6,30.7.

[0055] Example 2

[0056]

[0057] 1-(4-(tert-butyl)phenyl)-1H-benzo[d]imidazole (denoted as 1b, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3b. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried to obtain compound 3b (N 1 -(4-(tert-butyl)phenyl)-N 2 -Methylbenzene-1,2-diamine, yield 96%.

[0058] The characterization data of compound 3b are: 1 H NMR (400MHz, Chloroform-d) δ7.25-7.15(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 (101MHz, Chloroform-d) δ145.2,143.3,142.2,128.7,126.2,126.0,124.4,117.2,115.1,110.5,34.1,31.7,30.7.

[0059] Example 3

[0060]

[0061] 1-(4-methoxyphenyl)-1H-benzo[d]imidazole (denoted as 1c, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3c. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried to obtain compound 3c (N 1 -(4-methoxyphenyl)-N 2 -Methylbenzene-1,2-diamine, yield 88%.

[0062] The characterization data of compound 3c are: 1 H NMR(400MHz,Chloroform-d)δ7.07(t,J=7.6Hz,1H),7.01(d,J=7.6Hz,1H),6.79(d,J=8.9 Hz, 2H), 6.69 (dd, J = 12.3, 8.6Hz, 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] 1-(4-phenoxyphenyl)-1H-benzo[d]imidazole (denoted as 1d, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3d. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3d (N 1 -Methyl-N 2 -(4-Phenoxyphenyl)benzene-1,2-diamine, yield 98%.

[0066] The characterization data of compound 3d are: 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] 1-(4-(methylthio)phenyl)-1H-benzo[d]imidazole (denoted as 1e, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3e. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3e (N 1 -Methyl-N 2 -(4-(Methylthio)phenyl)benzene-1,2-diamine, yield 59%.

[0070] The characterization data of compound 3e are: 1 H NMR(400MHz,Chloroform-d)δ7.22-7.17(m,2H),7.14(td,J=7.7,1.5Hz,1H),7.08(dd,J=7.6,1.5Hz,1H), 6.69(td,J=10.0,8.7,1.7Hz,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 (101MHz, 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] 1-(4-fluorophenyl)-1H-benzo[d]imidazole (denoted as 1f, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried to obtain compound 3f (N 1 -(4-Fluorophenyl)-N 2 -Methylbenzene-1,2-diamine, yield 65%.

[0074] The characterization data of compound 3f are: 1 H NMR(400MHz,Chloroform-d)δ7.20(t,J=7.9Hz,2H),6.94(dd,J=11.0,8.2Hz,1H),6.84(t,J=7.3H z, 1H), 6.67 (d, J = 7.9Hz, 2H), 6.45 (dd, J = 12.6, 7.7Hz, 1H), 4.92 (s, 1H), 4.10 (s, 1H), 2.78 (s, 3H). 13 C NMR(101MHz,Chloroform-d)δ150.1(d,J=12.9Hz),147.7(d,J=12.9Hz),145.4,142.9(d,J=13.7Hz),142.6(dd,J=8.5,1.4Hz),140 .6(d,J=13.5Hz),129.6,123.2(dd,J=6.6,3.0Hz),119.9,115.2,114.2(d,J=1.0Hz),114.0(d,J=1.8Hz),99.2(d,J=22.1Hz),30.9. 19 F NMR (376MHz, Chloroform-d) δ-125.43 (tt, J=8.7, 4.6Hz).

[0075] Example 7

[0076]

[0077] 1-(2-naphthyl)-1H-benzo[d]imidazole (denoted as 1g, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred for 12h at 100°C under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried to obtain compound 3g (N 1 -Methyl-N 2 -(Naphthalene-2-yl)benzene-1,2-diamine, yield 81%.

[0078] The characterization data of compound 3g are: 1 H NMR(400MHz,Chloroform-d)δ7.68(t,J=7.8Hz,2H),7.54(d,J=8.2Hz,1H),7.33(ddd,J=8.2,6.8,1.3Hz,1H),7.27-7.1 0(m,3H),7.00(dd,J=8.8,2.4Hz,1H),6.86(d,J=2.3Hz,1H),6.78-6.67(m,2H),5.21(s,1H),4.16(s,1H),2.82(s,3H). 13 C NMR (101MHz, Chloroform-d) δ145.5,143.6,135.0,129.3,128.6,127.9,127.9,126.8,126.6,126.4,125.3,123.0,118.6,117.3,110.8,108.6,30.8.

[0079] Example 8

[0080]

[0081] 1-(1,2-methylenedioxyphenyl)-1H-benzo[d]imidazole (denoted as 1h, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3h. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3h (N 1 -(1,2-methylenedioxyphenyl)-N 2 -Methylbenzene-1,2-diamine, yield 93%.

[0082] The characterization data of compound 3h are: 1 H NMR(400MHz,Chloroform-d)δ7.09(t,J=7.7Hz,1H),7.03(d,J=7.5Hz,1H),6.67(dd,J=14.1,7.9Hz,3H) ,6.33(d,J=2.1Hz,1H),6.16(dd,J=8.3,2.1Hz,1H),5.86(s,2H),4.89(s,1H),4.09(s,1H),2.83(s,3H). 13 C NMR (101MHz, Chloroform-d) δ148.4,144.6,141.3,140.8,129.5,125.7,123.5,117.3,110.6,108.7,108.2,100.9,98.9,30.7.

[0083] Example 9

[0084]

[0085] 5,6-dimethyl-1-phenyl-1H-benzo[d]imidazole (denoted as 1i, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3i. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3i (N 1 ,4,5-Trimethyl-N 2 -Benzene-1,2-diamine, yield 77%.

[0086] The characterization data of compound 3i are: 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, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3j. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3j (4,5-dimethoxy-N 1 -Methyl-N 2 -Benzene-1,2-diamine, yield 76%.

[0090] The characterization data of compound 3j are: 1 H NMR(400MHz,Chloroform-d)δ7.18(t,J=7.8Hz,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 (101MHz, Chloroform-d) δ148.6,146.9,141.3,140.5,129.5,118.9,118.7,114.2,112.6,96.6,57.0,56.3,31.4.

[0091] Embodiment 11

[0092]

[0093] 5,6-difluoro-1-phenyl-1H-benzo[d]imidazole (denoted as 1k, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3k. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3k (4,5-difluoro-N 1 -Methyl-N 2 -Benzene-1,2-diamine, yield 98%.

[0094] The characterization data of compound 3k are: 1 H NMR(400MHz,Chloroform-d)δ7.20(t,J=7.9Hz,2H),6.94(dd,J=11.0,8.3Hz,1H),6.84(t,J=7.4H z, 1H), 6.66 (d, J = 7.7Hz, 2H), 6.45 (dd, J = 12.7, 7.7Hz, 1H), 4.92 (s, 1H), 4.09 (s, 1H), 2.78 (s, 3H). 13 C NMR(101MHz,Chloroform-d)δ150.1(d,J=13.0Hz),147.6(d,J=12.9Hz),145.4,142.9(d,J=13.5Hz),142.6(dd,J=8.5,1.6Hz ), 140.6 (d, J = 13.6Hz), 129.6, 123.2 (dd, J = 6.6, 3.0Hz), 119.9, 115.2, 114.1 (dd, J = 18.5, 1.8Hz), 99.1 (d, J = 22.1Hz), 30.8. 19 F NMR (376MHz, Chloroform-d) δ -140.53 (ddd, J=22.1, 12.6, 8.2Hz), -152.66 (ddd, J=22.9, 11.0, 7.6Hz).

[0095] Example 12

[0096]

[0097] 5,6-dichloro-1-phenyl-1H-benzo[d]imidazole (denoted as 1l, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3l. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3l (4,5-dichloro-N 1 -Methyl-N 2 -Benzene-1,2-diamine, yield 86%.

[0098] The characterization data of compound 31 are: 1 H NMR (400MHz, Chloroform-d) δ7.27-7.16 (m, 2H), 7.14 (s, 1H), 6.87 (t, J = 7.4Hz, 1H), 6.70 (d, J = 6.6Hz, 3H), 4.97 (s, 1H), 4.16 (s, 1H), 2.81 (s, 3H). 13 C NMR (101MHz, Chloroform-d) δ144.6,144.5,129.6,129.2,128.1,125.4,120.4,119.1,115.8,111.6,30.6.

[0099] Embodiment 13

[0100]

[0101] 5,6-dibromo-1-phenyl-1H-benzo[d]imidazole (denoted as 1m, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3m. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3m (4,5-dibromo-N1 -Methyl-N 2 -Benzene-1,2-diamine, yield 58%.

[0102] The characterization data of compound 3m are: 1 H NMR (400MHz, Chloroform-d) δ7.28 (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 (101MHz, Chloroform-d) δ145.1,144.5,129.6,129.0,128.2,121.1,120.4,115.9,114.7,110.0,30.5.

[0103] Embodiment 14

[0104]

[0105] 6-Chloro-4-methyl-1-phenyl-1H-benzo[d]imidazole (denoted as 1n, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under an argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3n. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3n (5-chloro-N 2 ,3-dimethyl-N 1 -Benzene-1,2-diamine, yield 87%.

[0106] The characterization data of compound 3n are: 1 H NMR(400MHz,Chloroform-d)δ7.29(t,J=7.8Hz,2H),7.13-7.01(m,3H),6.95(t,J=7. 4Hz, 1H), 6.70 (d, J = 2.0Hz, 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] Embodiment 15

[0108]

[0109] 1-Benzyl-1H-benzo[d]imidazole (denoted as 1o, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, concentration of 2mol / L) were added to a 10mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio of 1:1) were added and mixed, and stirred at 40°C for 4h to obtain a product system containing compound 3o. 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 volume ratio = 4:1 as an eluent, and the obtained eluate was decompressed and dried by spin drying to obtain compound 3o (N 1 -Benzyl-N 2 -Methylbenzene-1,2-diamine, yield 71%.

[0110] The characterization data of compound 3o are: 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. The only difference from Example 1 was that borane dimethyl sulfide complex was replaced by 9-BBN. Compound 3a was not detected, and only 1a was detected in the reaction solution.

[0113] Comparative Example 2

[0114] Compound 3a was prepared according to the method of Example 1. The only difference from Example 1 was that borane dimethyl sulfide complex was replaced by HBpin. Compound 3a was not detected, and only 1a was detected in the reaction solution.

[0115] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing N-phenylphenylenediamine compounds by structural reforming of imidazole compounds, comprising the following steps: The imidazole compound and the borane compound are mixed and subjected to reduction reaction in a protective atmosphere to obtain a boron nitrogen heterocyclic compound; The boron nitrogen heterocyclic compound is mixed with sodium perborate tetrahydrate and subjected to a ring-opening oxidation reaction to obtain an N-phenylphenylenediamine compound.

2. The preparation method according to claim 1, characterized in that: The imidazole compound has a structure shown in Formula 1: In Formula 1, R 1 Including phenyl, substituted aryl, naphthyl, benzobisoxazolyl or 1,2-methylenedioxyphenyl; R 2 Includes one or more of hydrogen, methyl, methoxy and halogen.

3. The preparation method according to claim 2, characterized in that: The substituents in the substituted aryl group include one or more of methyl, tert-butyl, methoxy, oxyphenyl, thiomethyl and fluorine.

4. The preparation method according to claim 1, characterized in that: 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.

5. The preparation method according to claim 1 or 4, characterized in that: The borane compounds include borane dimethyl sulfide complex and / or borane tetrahydrofuran complex.

6. The preparation method according to claim 1, characterized in that: The molar ratio of the imidazole compound to the borane compound is 1:3-5.

7. The preparation method according to claim 1, 2, 3, 4 or 6, characterized in that: The temperature of the reduction reaction is 80-100° C. and the time is 12-24 hours.

8. The preparation method according to claim 1, characterized in that: The molar ratio of the boron nitrogen heterocyclic compound to sodium perborate tetrahydrate is 1:3-5.

9. The preparation method according to claim 1, characterized in that: The temperature of the ring-opening oxidation reaction is 30-40° C. and the time is 4-6 hours.

Images