CN111909096A - Synthesis method of benzimidazole compound mediated by ammonium acetate - Google Patents
Synthesis method of benzimidazole compound mediated by ammonium acetate Download PDFInfo
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- CN111909096A CN111909096A CN202010774339.2A CN202010774339A CN111909096A CN 111909096 A CN111909096 A CN 111909096A CN 202010774339 A CN202010774339 A CN 202010774339A CN 111909096 A CN111909096 A CN 111909096A
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- phenylenediamine
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- ammonium acetate
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- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000005695 Ammonium acetate Substances 0.000 title claims abstract description 30
- 229940043376 ammonium acetate Drugs 0.000 title claims abstract description 30
- 235000019257 ammonium acetate Nutrition 0.000 title claims abstract description 30
- -1 benzimidazole compound Chemical class 0.000 title claims abstract description 30
- 238000001308 synthesis method Methods 0.000 title claims abstract description 10
- 230000001404 mediated effect Effects 0.000 title claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 89
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 20
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 14
- 239000000654 additive Substances 0.000 claims abstract description 12
- 230000000996 additive effect Effects 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000004440 column chromatography Methods 0.000 claims description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000003786 synthesis reaction Methods 0.000 claims description 4
- RXCOGDYOZQGGMK-UHFFFAOYSA-N (3,4-diaminophenyl)-phenylmethanone Chemical compound C1=C(N)C(N)=CC=C1C(=O)C1=CC=CC=C1 RXCOGDYOZQGGMK-UHFFFAOYSA-N 0.000 claims description 3
- ZOBQXWFQMOJTJF-UHFFFAOYSA-N 2-n-benzylbenzene-1,2-diamine Chemical compound NC1=CC=CC=C1NCC1=CC=CC=C1 ZOBQXWFQMOJTJF-UHFFFAOYSA-N 0.000 claims description 3
- RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 claims description 3
- NFCPRRWCTNLGSN-UHFFFAOYSA-N 2-n-phenylbenzene-1,2-diamine Chemical compound NC1=CC=CC=C1NC1=CC=CC=C1 NFCPRRWCTNLGSN-UHFFFAOYSA-N 0.000 claims description 3
- VWLLPPSBBHDXHK-UHFFFAOYSA-N 3,4-diaminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1N VWLLPPSBBHDXHK-UHFFFAOYSA-N 0.000 claims description 3
- AXNUJYHFQHQZBE-UHFFFAOYSA-N 3-methylbenzene-1,2-diamine Chemical compound CC1=CC=CC(N)=C1N AXNUJYHFQHQZBE-UHFFFAOYSA-N 0.000 claims description 3
- IWFHBRFJOHTIPU-UHFFFAOYSA-N 4,5-dichlorobenzene-1,2-diamine Chemical compound NC1=CC(Cl)=C(Cl)C=C1N IWFHBRFJOHTIPU-UHFFFAOYSA-N 0.000 claims description 3
- XSZYBMMYQCYIPC-UHFFFAOYSA-N 4,5-dimethyl-1,2-phenylenediamine Chemical compound CC1=CC(N)=C(N)C=C1C XSZYBMMYQCYIPC-UHFFFAOYSA-N 0.000 claims description 3
- BXIXXXYDDJVHDL-UHFFFAOYSA-N 4-Chloro-ortho-phenylenediamine Chemical compound NC1=CC=C(Cl)C=C1N BXIXXXYDDJVHDL-UHFFFAOYSA-N 0.000 claims description 3
- KWEWNOOZQVJONF-UHFFFAOYSA-N 4-fluorobenzene-1,2-diamine Chemical compound NC1=CC=C(F)C=C1N KWEWNOOZQVJONF-UHFFFAOYSA-N 0.000 claims description 3
- AGAHETWGCFCMDK-UHFFFAOYSA-N 4-methoxybenzene-1,2-diamine Chemical compound COC1=CC=C(N)C(N)=C1 AGAHETWGCFCMDK-UHFFFAOYSA-N 0.000 claims description 3
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 claims description 3
- UBPDKIDWEADHPP-UHFFFAOYSA-N 2-iodoaniline Chemical class NC1=CC=CC=C1I UBPDKIDWEADHPP-UHFFFAOYSA-N 0.000 claims description 2
- BYYYESJDKPVYGB-UHFFFAOYSA-N 4-bromo-5-methylbenzene-1,2-diamine Chemical compound CC1=CC(N)=C(N)C=C1Br BYYYESJDKPVYGB-UHFFFAOYSA-N 0.000 claims description 2
- WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 claims description 2
- DGRGLKZMKWPMOH-UHFFFAOYSA-N 4-methylbenzene-1,2-diamine Chemical compound CC1=CC=C(N)C(N)=C1 DGRGLKZMKWPMOH-UHFFFAOYSA-N 0.000 claims description 2
- RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 claims description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 2
- 239000001099 ammonium carbonate Substances 0.000 claims description 2
- 235000012501 ammonium carbonate Nutrition 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 238000011403 purification operation Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 150000008365 aromatic ketones Chemical class 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 35
- 229910052799 carbon Inorganic materials 0.000 abstract description 35
- 229910052751 metal Inorganic materials 0.000 abstract description 7
- 239000002184 metal Substances 0.000 abstract description 7
- 239000007800 oxidant agent Substances 0.000 abstract description 7
- 230000001590 oxidative effect Effects 0.000 abstract description 7
- 239000003054 catalyst Substances 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 238000001228 spectrum Methods 0.000 description 57
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 28
- 238000004809 thin layer chromatography Methods 0.000 description 28
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- 239000007789 gas Substances 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- 238000011221 initial treatment Methods 0.000 description 14
- 239000011259 mixed solution Substances 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
- 239000007858 starting material Substances 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 8
- 238000009987 spinning Methods 0.000 description 6
- 150000001556 benzimidazoles Chemical class 0.000 description 3
- 150000004987 o-phenylenediamines Chemical class 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010025 steaming 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
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing an ammonium acetate mediated benzimidazole compound. The synthesis method comprises the following steps: adding an o-phenylenediamine compound, dimethyl sulfoxide, an additive 1 and an additive 2 into a reaction tube, stirring at 130-150 ℃ for reaction, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the benzimidazole compound. The invention develops a method for synthesizing a benzimidazole compound under the mediation of ammonium acetate by using DMSO as a carbon source and an oxidant and using an o-phenylenediamine compound as a substrate under the condition of no metal catalyst. The synthesis method does not need a metal catalyst, and the required carbon source and oxidant have the characteristics of low toxicity, low price, easy obtainment, stable performance and the like. The method has the advantages of easy operation, few steps, mild reaction conditions, better functional group tolerance and the like, and provides a new valuable approach for synthesizing the benzimidazole compound.
Description
Technical Field
The invention belongs to the field of benzimidazole compounds, and particularly relates to a method for synthesizing an ammonium acetate mediated benzimidazole compound.
Background
The benzimidazole compound is a benzo heterocyclic compound containing two nitrogen atoms and is a structural unit of various medicaments. Many benzimidazole compounds have remarkable biological activity and have important medical value in the aspects of resisting tumors, cancers, viruses, bacteria, inflammation, parasites and the like. In addition to this, such compounds are also used for metal ligands. Just as benzimidazoles have such versatility, the methods for synthesizing such compounds have become a focus of research today.
The invention develops a method for synthesizing a benzimidazole compound under the mediation of ammonium acetate by taking DMSO as a carbon source and an oxidant and an o-phenylenediamine derivative as a substrate under the condition of no metal catalyst. The method has the advantages of few reaction steps, mild reaction conditions, higher functional group tolerance and the like, and develops a valuable path with simple operation, directness and atom economy for the synthesis of the benzimidazole compound.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a method for synthesizing an ammonium acetate mediated benzimidazole compound. The invention develops a method for synthesizing a benzimidazole compound under the mediation of ammonium acetate by taking DMSO as a carbon source and an oxidant and an o-phenylenediamine derivative as a substrate under the condition of no metal catalyst. The method has the advantages of few reaction steps, mild reaction conditions, higher functional group tolerance and the like, and develops a valuable path with simple operation, directness and atom economy for the synthesis of the benzimidazole compound.
The purpose of the invention is realized by the following technical scheme.
A method for synthesizing an ammonium acetate mediated benzimidazole compound comprises the following steps:
adding an o-phenylenediamine compound, dimethyl sulfoxide and an additive into a reaction tube, stirring and reacting at 130-150 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the benzimidazole compound.
Further, the chemical reaction equation of the synthesis process is as follows:
in the formula, R1One selected from hydrogen, methyl, methoxy, halogen, ester group, cyano, nitro and arone andthe above; r2One selected from methyl, benzyl and phenyl.
Further, the o-phenylenediamine compound is o-phenylenediamine, 3, 4-diaminotoluene, 4-methoxy-o-phenylenediamine, 4-fluoro-o-phenylenediamine, 4-chloro-o-phenylenediamine, 4-bromo-o-phenylenediamine, methyl 3, 4-diaminobenzoate, 4-cyano-o-phenylenediamine, 4-nitro-o-phenylenediamine, 3, 4-diaminobenzophenone, 2, 3-diaminotoluene, 4, 5-dimethyl-1, 2-phenylenediamine, 4-bromo-5-methylbenzene-1, 2-diamine, 4, 5-dichloro-1, 2-phenylenediamine, N-phenyl-o-phenylenediamine, N-methyl-o-phenylenediamine, N-benzyl-o-phenylenediamine.
Further, the amount of dimethyl sulfoxide added was 2 mL.
Further, the additive 1 is one of ammonium carbonate and ammonium acetate, and preferably ammonium acetate.
Furthermore, the molar ratio of the addition amount of the additive 1 to the o-iodoaniline derivative is 5-7: 1, and preferably 6: 1.
Further, the additive 2 is water; the addition amount of the additive 2 is 40-120 ul, and preferably 80 ul.
Further, the stirring temperature is 130-150 ℃, and preferably 140 ℃.
Further, the stirring reaction time is 9-15 hours, preferably 10 hours.
Further, the separation and purification operations are as follows: extracting the reaction liquid by using ethyl acetate, combining organic phases, drying by using anhydrous magnesium sulfate, filtering, decompressing, steaming and removing the organic solvent to obtain a crude product, and purifying by using column chromatography to obtain the 2-substituted benzimidazole compound.
The invention synthesizes the benzimidazole compound by using DMSO to provide a carbon source and an oxidant under the catalysis of no metal and using o-phenylenediamine as a substrate under the mediation of ammonium acetate through two times of C-N bond construction.
Compared with the prior art, the invention has the following advantages and beneficial effects:
the invention provides a method for synthesizing an ammonium acetate mediated benzimidazole compound. The invention provides a method for synthesizing a benzimidazole compound under the mediation of ammonium acetate by taking DMSO as a carbon source and an oxidant and an o-phenylenediamine derivative as a substrate under the condition of no metal catalyst. The carbon source and the oxidant required by the invention have the characteristics of low toxicity, low price, easy obtainment, stable performance and the like. The method has the advantages of few reaction steps, mild reaction conditions, higher functional group tolerance and the like, and provides a novel, easy-to-operate and green method for synthesizing the benzimidazole compound for synthesizing the benzimidazole.
Drawings
Fig. 1 and 2 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 1, respectively.
Fig. 3 and 4 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 2, respectively.
Fig. 5 and 6 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 3, respectively.
Fig. 7 and 8 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 4, respectively.
Fig. 9 and 10 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 5, respectively.
Fig. 11 and 12 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 6, respectively.
Fig. 13 and 14 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 7, respectively.
Fig. 15 and 16 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 8, respectively.
Fig. 17 and 18 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 9, respectively.
Fig. 19 and 20 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 10, respectively.
Fig. 21 and 22 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 11, respectively.
Fig. 23 and 24 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 12, respectively.
Fig. 25 and 26 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 13, respectively.
Fig. 27 and 28 are a hydrogen spectrum and a carbon spectrum of the objective product obtained in example 14, respectively.
Detailed description of the invention
The technical solutions of the present invention are further described in detail below with reference to specific examples and drawings, but the scope and implementation of the present invention are not limited thereto.
Example 1
O-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 10 hours at 140 ℃, and the reaction is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 56%.
The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 1 and fig. 2, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 8.14 (s, 1H), 7.68 (dd, J = 6.0 Hz, J = 3.0 Hz, 2H), 7.30 (dd, J = 6.0 Hz, J = 3.0 Hz, 2H), 7.20 (s, 1H); 13C NMR (CDCl3, 125 MHz) 140.68, 137.57, 122.91, 115.48。
the structure of the target product is presumed to be as follows through the data:
example 2
4-methoxy o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 35%.
The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 3 and 4, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 8.02 (s, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.10 (d, J = 2.0 Hz, 1H), 6.93 (dd, J = 8.5 Hz, J = 2.0 Hz, 1H), 3.83 (s, 3H); 13C NMR (CDCl3, 125 MHz) 156.60, 140.21, 137.59, 132.77, 116.49, 112.64, 97.52, 55.77。
the structure of the target product is presumed to be as follows through the data:
example 3
4-fluoro o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 78%.
The hydrogen spectrum and the carbon spectrum of the obtained target product are respectively shown in fig. 5 and 6, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 10.56 (s, 1H), 8.20 (s, 1H), 7.59 (dd, J = 9.0 Hz, J = 5.0 Hz, 1H), 7.33 (dd, J = 9.0 Hz, J = 2.0 Hz, 1H), 7.06 (td, J = 9.0 Hz, J = 2.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) 159.67 (d, J = 237.4 Hz), 141.77, 137.56 (d, J = 13.3 Hz), 134.38, 116.21 (d, J = 10.1 Hz), 111.45 (d, J = 25.5 Hz), 101.30 (d, J = 25.8 Hz)。
the structure of the target product is presumed to be as follows through the data:
example 4
4-chloro-o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 82%.
The hydrogen spectrum, the carbon spectrum and the fluorine spectrum of the obtained target product are respectively shown in fig. 7 and 8, and the nuclear magnetic data are as follows:
1H NMR (CDCl3, 500 MHz) 10.03 (s, 1H), 8.19 (s, 1H), 7.65 (d, J = 1.5 Hz, 1H), 7.58 (d, J = 8.5 Hz, 1H), 7.27 (dd, J = 8.5 Hz, J = 1.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) 141.73, 138.23, 136.25, 128.63, 123.60, 116.28, 115.28。
the structure of the target product is presumed to be as follows through the data:
example 5
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 9 and fig. 10, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 12.82 (s, 1H), 8.41 (s, 1H), 8.23(s, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.69 (s, 1H), 3.87(s, 3H); 13C NMR (CDCl3, 125 MHz) 167.27, 145.10, 137.30, 123.66, 121.23, 119.30, 113.93, 112.20, 52.45。
the structure of the target product is presumed to be as follows through the data:
example 6
4-cyano o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 57%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 11 and 12, and the nuclear magnetic data are as follows:
1H NMR (DMSO-d6,, 500 MHz) 13.01 (s, 1H), 8.49 (s, 1H), 8.17 (s, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H); 13C NMR (DMSO-d6, 125 MHz) 145.75, 139.85, 125.82, 121.92, 120.48, 116.46, 104.25。
the structure of the target product is presumed to be as follows through the data:
example 7
4-nitrophthalenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 71%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 13 and 14, and the nuclear magnetic data are as follows:
1H NMR (DMSO-d6, 500 MHz) 13.13 (s, 1H), 8.56 (s, 1H), 8.51 (d, J = 2.0 Hz, 1H), 8.11 (dd, J = 9.0 Hz, J = 2.0 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H); 13C NMR (DMSO-d6, 125 MHz) 147.19, 143.09, 142.07, 139.01, 118.04, 115.30, 113.21。
the structure of the target product is presumed to be as follows through the data:
example 8
3, 4-diaminobenzophenone (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the reaction is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 68%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 15 and 16, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 9.11 (s, 1H), 8.25 (s, 1H), 8.15 (s, 1H), 7.81-7.79 (m, 3H), 7.68 (d, J = 8.5 Hz, 1H), 7.58-7.55 (m, 1H), 7.47-7.44 (m, 2H); 13C NMR (CDCl3, 125 MHz) 197.34, 143.24, 140.54, 137.99, 137.67, 132.33, 130.00, 128.27, 125.24, 119.19, 115.00。
the structure of the target product is presumed to be as follows through the data:
example 9
2, 3-diaminotoluene (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 47%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 17 and fig. 18, and the nuclear magnetic data are as follows:
1H NMR (CDCl3, 500 MHz) 8.12 (s, 1H), 7.96 (s, 1H), 7.49 (d, J = 8.50 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.11 (d, J = 7.0 Hz, 1H), 2.63(s); 13C NMR (CDCl3, 125 MHz) 140.12, 137.68, 136.66, 125.96, 123.23, 122.95, 112.45。
the structure of the target product is presumed to be as follows through the data:
example 10
4, 5-dimethyl-1, 2-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, performing rotary powder chromatography to obtain a target product with the yield of 42%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 19 and fig. 20, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 8.00 (s, 1H), 7.43 (s, 2H), 6.49 (s, 1H); 13C NMR (CDCl3, 125 MHz) 139.74, 136.12, 131.91, 115.49, 20.37。
the structure of the target product is presumed to be as follows through the data:
example 11
4, 5-dichloro-1, 2-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the reaction is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 67%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 21 and 22, and the nuclear magnetic data are shown as follows:
1H NMR (DMSO-d6,, 500 MHz) 9.14 (s, 1H), 8.09 (s, 2H); 13C NMR (DMSO-d6, 125 MHz) 144.35, 133.73, 127.52, 116.92。
the structure of the target product is presumed to be as follows through the data:
example 12
N-phenyl o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, carrying out rotary powder chromatography to obtain a target product with the yield of 86%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 23 and 24, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 8.12 (s, 1H), 7.89-7.88 (m, 1H), 7.58-7.50 (m, 5H), 7.46 (t, J = 7.5 Hz, 1H), 7.36-7.31 (m, 2H); 13C NMR (CDCl3, 125 MHz) 143.88, 142.19, 136.21, 133.56, 129.98, 127.96, 123.95, 123.63, 122.73, 120.49, 110.40。
the structure of the target product is presumed to be as follows through the data:
example 13
N-methyl o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) are sequentially added into a dry Schlenk reaction tube, after the sample is added, an oil pump is used for vacuumizing, nitrogen is injected for gas replacement, after three times of replacement, the reaction is stopped after 11 hours at 140 ℃, and the temperature is cooled to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 67%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 25 and 26, and the nuclear magnetic data are shown as follows:
1H NMR (CDCl3, 500 MHz) 7.85 (s, 1H), 7.80 (d, J = 7.5 Hz, 1H), 7.38 (d, J = 7.5 Hz, 1H), 7.33-7.27 (m, 2H), 3.81 (s, 3H); 13C NMR (CDCl3, 125 MHz) 143.47, 143.43, 134.39, 122.86, 122.04, 120.10, 109.29, 30.95。
the structure of the target product is presumed to be as follows through the data:
example 14
Sequentially adding N-benzyl o-phenylenediamine (0.2 mmol), dimethyl sulfoxide (2 mL), ammonium acetate (1.2 mmol) and water (80 ul) into a dry Schlenk reaction tube, vacuumizing by using an oil pump after the sample is added, injecting nitrogen for gas replacement, reacting for 11 hours at 140 ℃ after the gas replacement is carried out for three times, stopping, and cooling to room temperature. The reaction was monitored by Thin Layer Chromatography (TLC) and when the starting material had reacted, the reaction was terminated and the mixture was cooled to room temperature in the reaction tube. Carrying out primary treatment on the mixed solution: and (3) extracting, collecting an organic layer, spinning powder, and performing column chromatography to obtain a target product with the yield of 65%.
The obtained hydrogen spectrum and carbon spectrum of the target product are respectively shown in fig. 27 and 28, and the nuclear magnetic data are shown as follows:
1H NMR (DMSO-d6, 500 MHz) 7.94 (s, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.34-7.23(m, 6H), 7.17 (d, J = 7.0 Hz, 2H); 13C NMR (DMSO-d6, 125 MHz) 143.84, 143.15, 135.37, 133.82, 128.95, 128.17, 126.99, 123.01, 122.20, 120.32, 109.97, 48.73。
the structure of the target product is presumed to be as follows through the data:
Claims (9)
1. a method for synthesizing an ammonium acetate mediated benzimidazole compound is characterized by comprising the following steps:
adding an o-phenylenediamine compound, dimethyl sulfoxide and an additive into a reaction tube, stirring and reacting at 130-150 ℃, cooling to room temperature after the reaction is finished, and separating and purifying a product to obtain the benzimidazole compound.
2. The method of claim 1, wherein the chemical reaction equation of the synthesis process is as follows:
in the formula, R1One or more selected from hydrogen, methyl, methoxy, halogen group, ester group, cyano, nitro and aromatic ketone; r2One selected from methyl, benzyl and phenyl.
3. The method according to claim 1 or 2, wherein the o-phenylenediamine compound is o-phenylenediamine, 3, 4-diaminotoluene, 4-methoxyphenylenediamine, 4-fluorophenylenediamine, 4-chlorophenylenediamine, 4-bromoo-phenylenediamine, methyl 3, 4-diaminobenzoate, 4-cyanophenylenediamine, 4-nitrophenylenediamine, 3, 4-diaminobenzophenone, 2, 3-diaminotoluene, 4, 5-dimethyl-1, 2-phenylenediamine, 4-bromo-5-methylbenzene-1, 2-diamine, 4, 5-dichloro-1, 2-phenylenediamine, N-phenylphenylenediamine, N-methylphenylenediamine, N-benzylo-phenylenediamine.
4. A synthesis method according to claims 1-3, characterized in that the dimethyl sulfoxide is 2 ml.
5. The synthesis method according to claims 1-3, wherein the additive 1 is one of ammonium carbonate and ammonium acetate; the molar ratio of the addition amount of the additive 1 to the o-iodoaniline derivative is 5-7: 1.
6. A synthesis method according to claims 1-3, characterized in that the additive 2 is water; the addition amount of the additive 2 is 40-120 ul.
7. The synthesis method according to claims 1 to 3, characterized in that the stirring temperature is 130 to 150 ℃.
8. The synthesis method according to claims 1 to 3, wherein the reaction time is 8 to 12 hours.
9. The synthesis method according to claims 1 to 3, characterized in that the separation and purification operations are: and extracting the reaction liquid by using ethyl acetate, combining organic phases, drying by using anhydrous magnesium sulfate, filtering, distilling under reduced pressure to remove the organic solvent to obtain a crude product, and purifying by using column chromatography to obtain the benzimidazole compound.
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