CN112500352A - N-substituted bis-benzimidazole diamine and preparation method thereof - Google Patents
N-substituted bis-benzimidazole diamine and preparation method thereof Download PDFInfo
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- -1 bis-benzimidazole diamine Chemical class 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 238000006482 condensation reaction Methods 0.000 claims abstract description 18
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 18
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 239000011230 binding agent Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 8
- 239000012445 acidic reagent Substances 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 150000004702 methyl esters Chemical class 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims description 3
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000178 monomer Substances 0.000 abstract description 10
- 150000004985 diamines Chemical class 0.000 abstract description 8
- 229920000642 polymer Polymers 0.000 abstract description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 229920001002 functional polymer Polymers 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 27
- 238000001914 filtration Methods 0.000 description 16
- 238000001035 drying Methods 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- 239000007788 liquid Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- OGBINJLTBZWRRB-UHFFFAOYSA-N methyl 2,2,2-trichloroethanimidate Chemical compound COC(=N)C(Cl)(Cl)Cl OGBINJLTBZWRRB-UHFFFAOYSA-N 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- MNIKERWISBANET-UHFFFAOYSA-N 1-n-methyl-4-nitrobenzene-1,2-diamine Chemical compound CNC1=CC=C([N+]([O-])=O)C=C1N MNIKERWISBANET-UHFFFAOYSA-N 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000005311 nuclear magnetism Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 238000005034 decoration Methods 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 229920002396 Polyurea Polymers 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/20—Two benzimidazolyl-2 radicals linked together directly or via a hydrocarbon or substituted hydrocarbon radical
Abstract
The invention relates to the technical field of organic synthesis, and provides N-substituted bis-benzimidazole diamine and a preparation method thereof. The N-substituted bis-benzimidazole diamine provided by the invention is a novel diamine monomer, and the N position of a benzimidazole ring has multiple side groups, so that different performances can be brought to the diamine monomer, and a polymer with new functions can be synthesized, and the N-substituted bis-benzimidazole diamine has a wide application prospect in the field of synthesis of functional polymers. The invention also provides a preparation method of the N-substituted bis-benzimidazole diamine, the N-substituted bis-benzimidazole diamine with the structure shown in the formula I can be obtained by taking the compound with the structure shown in the formula a as an initial raw material through condensation reaction, ring closing reaction and catalytic hydrogenation reaction, and the synthetic route is simple and easy to operate.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to N-substituted bis-benzimidazole diamine and a preparation method thereof.
Background
Diamine compounds are important chemical raw materials or intermediates, and can be used as monomers for synthesizing various polymers such as novel polyimide, polyamide, polyurea, organic silicon and the like. The introduction of aromatic heterocyclic structure and different side groups in diamine can effectively improve the mechanical property, chemical corrosion resistance, high temperature resistance and solubility of the material, thereby expanding the application field of the material.
Benzimidazole diamine is taken as a typical rigid aromatic heterocyclic unit and is introduced into a high molecular main chain, so that the mechanical property and the heat resistance of the material can be obviously improved. However, the benzimidazole diamine monomer in the prior art has a single structure, and cannot meet the requirements for synthesizing polymers with different performances, and the construction of diamine monomers with different structures is a research hotspot in the art.
Disclosure of Invention
In view of the above, the present invention provides a novel N-substituted bis-benzimidazole diamine and a preparation method thereof. The diamine monomer provided by the invention is N-substituted bis-benzimidazole diamine, and various side groups are introduced into the N position of a benzimidazole ring, so that the structure is variable, the disadvantage of single structure of the diamine monomer in the prior art can be solved, and new performance and functions are brought to materials.
In order to achieve the above object, the present invention provides the following technical solutions:
an N-substituted bis-benzimidazole diamine has a structure shown in formula I:
in formula I: x is one of the following groups:
preferably, the N-substituted bis-benzimidazole diamine has one of the following structures:
preferably, the N-substituted bis-benzimidazole diamine has one of the following structures:
the invention provides a preparation method of N-substituted bis-benzimidazole diamine, which comprises the following steps:
(1) carrying out condensation reaction on a compound with a structure shown in a formula a and 2,2, 2-trichloroacetimido methyl ester to obtain a compound with a structure shown in a formula b;
(2) carrying out a ring closing reaction on a compound with a structure shown in a formula b and a compound with a structure shown in a formula c to obtain a compound with a structure shown in a formula d;
the type of X in the formula c and the formula d is consistent with that in the formula I;
(3) and (3) carrying out catalytic hydrogenation reaction on the compound with the structure shown in the formula d under the hydrogen condition to obtain the N-substituted bis-benzimidazole diamine with the structure shown in the formula I.
Preferably, the condensation reaction is carried out under the condition of an acidic reagent, and the acidic reagent comprises one or more of acetic acid, hydrochloric acid and sulfuric acid.
Preferably, the condensation reaction is carried out at the temperature of 10-30 ℃ for 10-12 h.
Preferably, the ring closing reaction is carried out in the presence of an acid-binding agent, wherein the acid-binding agent comprises one or more of triethylamine, diisopropylethylamine, pyridine, sodium carbonate, sodium bicarbonate and potassium carbonate; the solvent for ring closing reaction comprises one or more of ethanol, methanol, dichloroethane, dichloromethane, benzene, toluene, chloroform, carbon tetrachloride and tetrahydrofuran.
Preferably, the temperature of the ring closing reaction is 50-100 ℃, and the time is 20-24 h.
Preferably, the catalyst for catalytic hydrogenation reaction comprises one or more of palladium carbon, platinum carbon, active nickel and rhodium carbon;
the solvent for catalytic hydrogenation reaction comprises one or more of tetrahydrofuran, ethanol, methanol, isopropanol, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, 1, 4-dioxane, ethyl acetate, benzene, toluene and xylene.
Preferably, the temperature of the catalytic hydrogenation reaction is 40-100 ℃, the pressure is 0.5-3 MPa, and the reaction time is 5-6 h.
The invention provides N-substituted bis-benzimidazole diamine which has a structure shown in a formula I. The N-substituted bis-benzimidazole diamine provided by the invention is a novel diamine monomer, a plurality of side groups are introduced into the N position of a benzimidazole ring, the structure is variable, the disadvantage of single structure of the diamine monomer in the prior art can be solved, the N-substituted bis-benzimidazole diamine monomer provided by the invention is used for synthesizing a polymer, the obtained material can keep various advantages of the original benzimidazole material, and the N position of the benzimidazole ring is introduced with a plurality of side groups, so that new performance and functions can be brought to the material. The N-substituted bis-benzimidazole diamine provided by the invention has wide application prospect in the field of polymer synthesis.
The invention also provides a preparation method of the N-substituted bis-benzimidazole diamine, which takes the compound with the structure shown in the formula a as the initial raw material, and the N-substituted bis-benzimidazole diamine with the structure shown in the formula I can be obtained through condensation reaction, ring closing reaction and catalytic hydrogenation reaction. The preparation method provided by the invention has the advantages of cheap and easily available raw materials, high process safety, simple and convenient operation, low production cost and high reaction yield, and is suitable for industrial production.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of N-methyl-5, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole prepared in example 1;
FIG. 2 is a nuclear magnetic hydrogen spectrum of N-methyl-6, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole prepared in example 2;
FIG. 3 is a nuclear magnetic hydrogen spectrum of N-phenyl-5, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole prepared in example 3.
Detailed Description
The invention provides N-substituted bis-benzimidazole diamine, which has a structure shown in a formula I:
in formula I: x is one of the following groups:
in the present invention, the two amino groups in the structure represented by formula I are preferably located at the 5-or 6-position and the 5 '-or 6' -position of the N-substituted benzimidazole unit and the para-benzimidazole unit, respectively, i.e., the N-substituted bisbenzimidazole diamine preferably has one of the following structures:
in the present invention, the N-substituted bisbenzimidazole diamine preferably has one of the following structures:
the invention also provides a preparation method of the N-substituted bis-benzimidazole diamine, which comprises the following steps:
(1) carrying out condensation reaction on a compound with a structure shown in a formula a and 2,2, 2-trichloroacetimido methyl ester to obtain a compound with a structure shown in a formula b;
(2) carrying out a ring closing reaction on a compound with a structure shown in a formula b and a compound with a structure shown in a formula c to obtain a compound with a structure shown in a formula d;
the type of X in the formula c and the formula d is consistent with that in the formula I;
(3) and (3) carrying out catalytic hydrogenation reaction on the compound with the structure shown in the formula d under the hydrogen condition to obtain the N-substituted bis-benzimidazole diamine with the structure shown in the formula I.
The synthetic route of the N-substituted bis-benzimidazole diamine is shown as a formula A, and the specific description is carried out by combining the formula A, wherein the type of the X group in the formula A is the same as that in the formula I.
The compound with the structure shown in the formula a and 2,2, 2-trichloroacetimido methyl ester are subjected to condensation reaction to obtain the compound with the structure shown in the formula b. In the embodiment of the invention, the compound with the structure shown in the formula a is preferably 4-nitro-1, 2-phenylenediamine, and the compound with the structure shown in the formula b is preferably 2-trichloromethyl-5 (6) -nitrobenzimidazole; in the invention, the molar ratio of the compound having the structure shown in the formula a to methyl 2,2, 2-trichloroacetimidate is preferably 1.0-1.2: 1, and more preferably 1.1: 1.
In the invention, the condensation reaction is preferably carried out under the condition of an acidic reagent, and the acidic reagent preferably comprises one or more of acetic acid, hydrochloric acid and sulfuric acid; the dosage of the compound with the structure shown in the formula a and the acidic reagent is preferably 1 g: 10-11 mL, more preferably 1 g: 10 mL.
In the invention, the temperature of the condensation reaction is preferably 10-30 ℃, more preferably 15-25 ℃, and in the specific embodiment of the invention, the condensation reaction is preferably performed at room temperature; the time of the condensation reaction is preferably 10-12 h; in a particular embodiment of the invention, the end of the reaction is preferably monitored by TLC.
In the embodiment of the invention, preferably, the compound having the structure shown in formula a and the acidic reagent are mixed, the mixture is cooled to 10 +/-1 ℃, then the methyl 2,2, 2-trichloroacetimidate is added dropwise, and after the addition is finished, the temperature is raised to the condensation reaction temperature for reaction. The invention preferably finishes dripping the 2,2, 2-trichloroacetimidate methyl ester within 0.5-1 h.
After the condensation reaction is completed, the invention preferably carries out post-treatment on the obtained product feed liquid, and the post-treatment preferably comprises the following steps:
mixing the product liquid obtained by the condensation reaction with water, and then carrying out solid-liquid separation to obtain a crude product; and (3) recrystallizing the crude product by using ethanol, and then sequentially carrying out solid-liquid separation and drying to obtain the compound with the structure shown in the formula b.
The invention has no special requirements on the dosage of water, the specific conditions of recrystallization, solid-liquid separation and drying, and the conditions which are well known by the technicians in the field can be adopted.
After the compound with the structure shown in the formula b is obtained, the compound with the structure shown in the formula b and the compound with the structure shown in the formula c are subjected to ring closing reaction to obtain the compound with the structure shown in the formula d.
In the invention, the ring closing reaction is preferably carried out in the presence of an acid-binding agent, wherein the acid-binding agent preferably comprises one or more of triethylamine, diisopropylethylamine, pyridine, sodium carbonate, sodium bicarbonate and potassium carbonate;
in the present invention, the molar ratio of the compound having the structure represented by formula b to the compound having the structure represented by formula c is preferably 1: 2.0-2.5, preferably 1: 2.2; the molar ratio of the compound having the structure represented by the formula b to the acid-binding agent is preferably 1: 1.0-1.5, and more preferably 1: 1.2.
In the present invention, the solvent for the ring closure reaction preferably includes one or more of ethanol, methanol, dichloroethane, dichloromethane, benzene, toluene, chloroform, carbon tetrachloride and tetrahydrofuran; the invention has no special requirements on the dosage of the solvent, and can ensure that the reaction is carried out smoothly.
In the invention, the temperature of the ring closing reaction is preferably 50-100 ℃, more preferably 60-80 ℃, and the time of the ring closing reaction is preferably 20-24 h; in a particular embodiment of the invention, the end of the reaction is preferably monitored by TLC.
In the specific embodiment of the invention, the compound having the structure shown in the formula b, the compound having the structure shown in the formula c and the solvent are preferably mixed, the mixture is heated to 80 +/-1 ℃, then the acid-binding agent is dropwise added, and the mixture is heated to the ring-closing reaction temperature after the dropwise addition is finished to carry out the reaction. The acid-binding agent is preferably added dropwise within 1-2 h.
After the ring-closing reaction is finished, the obtained product feed liquid is preferably subjected to post-treatment, the post-treatment method is preferably consistent with the post-treatment method of the condensation reaction product feed liquid, and only a recrystallization reagent is replaced by N, N-dimethylacetamide (DMAc).
After the compound with the structure shown in the formula d is obtained, the compound with the structure shown in the formula d is subjected to catalytic hydrogenation reaction under the hydrogen condition to obtain the N-substituted bis-benzimidazole diamine with the structure shown in the formula I. In the invention, the catalyst for catalytic hydrogenation reaction preferably comprises one or more of palladium carbon, platinum carbon, active nickel and rhodium carbon; the mass ratio of the catalyst to the compound having the structure represented by the formula d is preferably 0.1-0.15: 1, more preferably 0.1: 1.
in the present invention, the solvent for hydrogenation reaction preferably includes one or more of tetrahydrofuran, ethanol, methanol, isopropanol, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, 1, 4-dioxane, ethyl acetate, benzene, toluene, and xylene. The method has no special requirement on the dosage of the solvent, and can ensure the smooth operation of the hydrogenation reaction.
In the invention, the temperature of the catalytic hydrogenation reaction is preferably 40-100 ℃, more preferably 60-80 ℃, the pressure is preferably 0.5-3 MPa, more preferably 1-2 MPa, and the reaction time is preferably 5-6 h, and in the specific embodiment of the invention, TLC is preferably used for monitoring the reaction completion; the catalytic hydrogenation reaction is preferably carried out in an autoclave.
In the embodiment of the present invention, it is preferable that the compound having the structure represented by formula d, the solvent and the catalyst are first charged into the autoclave, then the air in the autoclave is replaced with nitrogen three times, and then hydrogen is charged to perform the reaction.
After the catalytic hydrogenation reaction is finished, the invention preferably carries out post-treatment on the obtained product feed liquid, and the post-treatment preferably comprises the following steps: and (2) filtering a product liquid obtained by catalytic hydrogenation reaction, recovering the catalyst, and sequentially cooling, crystallizing, filtering and drying the obtained filtrate to obtain the N-substituted bis-benzimidazole diamine with the structure shown in the formula I. In the invention, the cooling crystallization temperature is preferably 20-25 ℃.
The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
In this example, the specific structure of N-substituted bis-benzimidazole diamine is as follows, with the generic name N-methyl-5, 5 ' (6 ') -diamino-2, 2 ' -bis-benzimidazole:
the preparation method of the N-methyl-5, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole comprises the following steps:
(1) adding 50.0g of 4-nitro-1, 2-phenylenediamine and 500.0g of acetic acid into a reaction bottle, cooling to 10 +/-1 ℃, dropwise adding 69.1g of methyl 2,2, 2-trichloroacetimidate, completing dropwise adding for 0.5-1 h, reacting for 12h at room temperature, and determining the reaction to be finished by TLC. Adding 1500.0g of water into the product feed liquid, carrying out vacuum suction filtration to obtain 85g of a crude product, recrystallizing by using ethanol, filtering, and drying to obtain 68.9g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, wherein the yield is as follows: 84.3 percent.
(2) Adding 65.0g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, 43.4g N1-methyl-4-nitro-1, 2-phenylenediamine and 650.0g of ethanol into a reaction bottle provided with a reflux condensing device, heating to 80 +/-1 ℃, dropwise adding 39.4g of triethylamine, completing dropwise adding within 1-2 h, reacting at 80-85 ℃ for 24h, and determining the reaction to be finished by TLC. Adding 2000.0g of water into the reaction system, carrying out vacuum filtration to obtain 83g of a crude product, recrystallizing by DMAc, filtering, and drying to obtain 71.6g N-methyl-5, 5 ' (6 ') -dinitro-2, 2 ' -bibenzimidazole, wherein the yield is as follows: 83.2 percent.
(3) Adding 65.0g N-methyl-5, 5 '(6') -dinitro-2, 2 '-bibenzimidazole, 650.0g dioxane and 6.5g palladium carbon into an autoclave, replacing three times by nitrogen, then filling hydrogen to the pressure of 0.7-0.8 MPa, controlling the temperature at 50-60 ℃, keeping the temperature and maintaining the pressure for 5 hours, filtering and recovering the catalyst after TLC (thin layer chromatography) is determined to finish the reaction, cooling and crystallizing the filtrate, filtering and drying to obtain 50.4g N-methyl-5, 5' (6 ') -diamino-2, 2' -bibenzimidazole, wherein the yield is 94.2%. The nuclear magnetism hydrogen spectrum of the product is shown in figure 1.
Example 2
In this example, the specific structure of N-substituted bis-benzimidazole diamine is as follows, with the generic name N-methyl-6, 5 ' (6 ') -diamino-2, 2 ' -bis-benzimidazole:
the preparation method of the N-methyl-6, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole comprises the following steps:
(1) adding 50.0g of 4-nitro-1, 2-phenylenediamine and 500.0g of acetic acid into a reaction bottle, cooling to 10 +/-1 ℃, dropwise adding 69.1g of methyl 2,2, 2-trichloroacetimidate, completing dropwise adding for 0.5-1 h, reacting for 12h at room temperature, and determining the reaction to be finished by TLC. Adding 1500.0g of water into a reaction system, carrying out vacuum filtration to obtain 85g of a crude product, recrystallizing with ethanol, filtering, and drying to obtain 68.9g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, wherein the yield is as follows: 84.3 percent.
(2) Adding 65.0g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, 43.4g N1-methyl-4-nitro-1, 2-phenylenediamine and 650.0g of ethanol into a reaction bottle provided with a reflux condensing device, heating to 80 +/-1 ℃, dropwise adding 39.4g of triethylamine, completing dropwise adding within 1-2 h, reacting at 80-85 ℃ for 24h, and determining the reaction to be finished by TLC. Adding 2000.0g of water into the reaction system, decompressing and filtering to obtain 83g of crude product, recrystallizing by DMAc, filtering, and drying to obtain 71.6g N-methyl-6, 5 ' (6 ') -dinitro-2, 2 ' -bibenzimidazole, wherein the yield is as follows: 81.6 percent.
(3) Adding 70.0g N-methyl-6, 5 '(6') -dinitro-2, 2 '-bibenzimidazole, 700.0g dioxane and 7.0g palladium carbon into an autoclave, replacing three times by nitrogen, then filling hydrogen to the pressure of 0.7-0.8 MPa, controlling the temperature at 50-60 ℃, keeping the temperature and maintaining the pressure for 5 hours, filtering to recover the catalyst after TLC is determined to be finished, cooling and crystallizing the filtrate, filtering, and drying to obtain 54.5g 1-methyl-6, 5' (6 ') -diamino-2, 2' -bibenzimidazole, wherein the yield is 94.7%, and the nuclear magnetic spectrum is confirmed by nuclear magnetism of the product structure and is shown in figure 2.
Example 3
In this example, the specific structure of N-substituted bis-benzimidazole diamine is as follows, with the generic name N-phenyl-5, 5 ' (6 ') -diamino-2, 2 ' -bis-benzimidazole:
the preparation method of the N-phenyl-5, 5 ' (6 ') -diamino-2, 2 ' -bibenzimidazole comprises the following steps:
(1) adding 50.0g of 4-nitro-1, 2-phenylenediamine and 500.0g of acetic acid into a reaction bottle, cooling to 10 +/-1 ℃, dropwise adding 69.1g of methyl 2,2, 2-trichloroacetimidate, completing dropwise adding for 0.5-1 h, reacting for 12h at room temperature, and determining the reaction to be finished by TLC. Adding 1500.0g of water into a reaction system, carrying out vacuum filtration to obtain 85g of a crude product, recrystallizing with ethanol, filtering, and drying to obtain 68.9g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, wherein the yield is as follows: 84.3 percent.
(2) Adding 65.0g of 2-trichloromethyl-5 (6) -nitrobenzimidazole, 59.5g N1-methyl-4-nitro-1, 2-phenylenediamine and 650.0g of ethanol into a reaction bottle provided with a reflux condensing device, heating to 80 +/-1 ℃, dropwise adding 39.4g of triethylamine, completing dropwise adding within 1-2 h, reacting at 80-85 ℃ for 24h, and determining the reaction to be finished by TLC. Adding 2000.0g of water into the reaction system, decompressing and filtering to obtain 98g of crude product, recrystallizing by DMAc, filtering, and drying to obtain 82.6g N-phenyl-5, 5 ' (6 ') -dinitro-2, 2 ' -bibenzimidazole, wherein the yield is as follows: 79.5 percent.
(3) Adding 80.0g N-phenyl-5, 5 '(6') -dinitro-2, 2 '-bibenzimidazole, 800.0g of 1,4 dioxane and 8.0g of palladium carbon into an autoclave, replacing three times by nitrogen, then filling hydrogen to the pressure of 0.7-0.8 MPa, controlling the temperature at 50-60 ℃, keeping the temperature and maintaining the pressure for 5 hours, confirming the reaction by TLC, filtering and recovering the catalyst, cooling and crystallizing the filtrate, filtering and drying to obtain 61.4g N-phenyl-5, 5' (6 ') -diamino-2, 2' -bibenzimidazole, wherein the yield is 90.2%, and the nuclear magnetic spectrum is confirmed by nuclear magnetism of the product structure and is shown in figure 3.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. An N-substituted bis-benzimidazole diamine, characterized by having the structure shown in formula I:
in formula I: x is one of the following groups:
2. the N-substituted bisbenzimidazole diamine of claim 1, wherein the N-substituted bisbenzimidazole diamine has one of the following structures:
3. the N-substituted bisbenzimidazole diamine of claim 1, wherein the N-substituted bisbenzimidazole diamine has one of the following structures:
4. a method for producing an N-substituted bisbenzimidazole diamine according to any one of claims 1 to 3, comprising the steps of:
(1) carrying out condensation reaction on a compound with a structure shown in a formula a and 2,2, 2-trichloroacetimido methyl ester to obtain a compound with a structure shown in a formula b;
(2) carrying out a ring closing reaction on a compound with a structure shown in a formula b and a compound with a structure shown in a formula c to obtain a compound with a structure shown in a formula d;
the type of X in the formula c and the formula d is consistent with that in the formula I;
(3) and (3) carrying out catalytic hydrogenation reaction on the compound with the structure shown in the formula d under the hydrogen condition to obtain the N-substituted bis-benzimidazole diamine with the structure shown in the formula I.
5. The method according to claim 4, wherein the condensation reaction is carried out under an acidic reagent comprising one or more of acetic acid, hydrochloric acid and sulfuric acid.
6. The preparation method according to claim 4 or 5, wherein the condensation reaction is carried out at a temperature of 10-30 ℃ for 10-12 hours.
7. The preparation method of claim 4, wherein the ring closing reaction is carried out in the presence of an acid-binding agent, wherein the acid-binding agent comprises one or more of triethylamine, diisopropylethylamine, pyridine, sodium carbonate, sodium bicarbonate and potassium carbonate; the solvent for ring closing reaction comprises one or more of ethanol, methanol, dichloroethane, dichloromethane, benzene, toluene, chloroform, carbon tetrachloride and tetrahydrofuran.
8. The preparation method according to claim 4 or 7, wherein the temperature of the ring closing reaction is 50-100 ℃ and the time is 20-24 h.
9. The preparation method according to claim 4, wherein the catalyst for catalytic hydrogenation reaction comprises one or more of palladium carbon, platinum carbon, active nickel and rhodium carbon;
the solvent for catalytic hydrogenation reaction comprises one or more of tetrahydrofuran, ethanol, methanol, isopropanol, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, 1, 4-dioxane, ethyl acetate, benzene, toluene and xylene.
10. The preparation method according to claim 4 or 9, wherein the temperature of the catalytic hydrogenation reaction is 40-100 ℃, the pressure is 0.5-3 MPa, and the reaction time is 5-6 h.
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| WO2007056155A1 (en) * | 2005-11-03 | 2007-05-18 | Chembridge Research Laboratories, Inc. | Heterocyclic compounds as tyrosine kinase modulators |
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| CN110577500A (en) * | 2019-10-01 | 2019-12-17 | 常州市阳光药业有限公司 | Preparation method of 2- (aminophenyl) -5-aminobenzoxazole |
| CN111286195A (en) * | 2020-02-19 | 2020-06-16 | 东华大学 | Polyimide film containing bisbenzoxazole unit and preparation method and application thereof |
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| WO2007056155A1 (en) * | 2005-11-03 | 2007-05-18 | Chembridge Research Laboratories, Inc. | Heterocyclic compounds as tyrosine kinase modulators |
| CN107021930A (en) * | 2017-05-12 | 2017-08-08 | 常州市阳光药业有限公司 | Synthesize 1H, 1`H（2,2` bisbenzimidazoles）The method of 5,5` diamines |
| CN110577500A (en) * | 2019-10-01 | 2019-12-17 | 常州市阳光药业有限公司 | Preparation method of 2- (aminophenyl) -5-aminobenzoxazole |
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