CN116621781A - Preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline - Google Patents
Preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline Download PDFInfo
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- CN116621781A CN116621781A CN202210125419.4A CN202210125419A CN116621781A CN 116621781 A CN116621781 A CN 116621781A CN 202210125419 A CN202210125419 A CN 202210125419A CN 116621781 A CN116621781 A CN 116621781A
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- imidazoline
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- -1 3-nitrophenyl Chemical group 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims abstract description 24
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000007787 solid Substances 0.000 claims abstract description 16
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000001914 filtration Methods 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 12
- 239000005051 trimethylchlorosilane Substances 0.000 claims abstract description 12
- 230000035484 reaction time Effects 0.000 claims abstract description 10
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 125000000532 dioxanyl group Chemical group 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 9
- YSCJJOXSVFNSPY-UHFFFAOYSA-N 2-(3-nitrophenyl)-4,5-dihydro-1h-imidazole Chemical compound [O-][N+](=O)C1=CC=CC(C=2NCCN=2)=C1 YSCJJOXSVFNSPY-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 239000002994 raw material Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- 239000011593 sulfur Substances 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- RUSAWEHOGCWOPG-UHFFFAOYSA-N 3-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=CC(C#N)=C1 RUSAWEHOGCWOPG-UHFFFAOYSA-N 0.000 description 4
- ROYGEONSPSZKNF-UHFFFAOYSA-N N1C=NC=C1.C1(=CC=CC=C1)NC(=O)N Chemical compound N1C=NC=C1.C1(=CC=CC=C1)NC(=O)N ROYGEONSPSZKNF-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- SCEVFJUWLLRELN-UHFFFAOYSA-N imidocarb Chemical compound C=1C=CC(C=2NCCN=2)=CC=1NC(=O)NC(C=1)=CC=CC=1C1=NCCN1 SCEVFJUWLLRELN-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- QYEMLLMAPAWTPT-UHFFFAOYSA-N 1h-imidazol-2-ylurea Chemical compound NC(=O)NC1=NC=CN1 QYEMLLMAPAWTPT-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 201000008680 babesiosis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229960004683 imidocarb Drugs 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 206010035485 plasmacytosis Diseases 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000273 veterinary drug Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The application discloses a preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline, which comprises the following steps: dissolving m-nitrobenzaldehyde, ethylenediamine and trimethylchlorosilane in an aprotic solvent, heating under the protection of nitrogen, reacting, cooling to room temperature after the reaction is finished, adding water to separate out solid, and filtering to obtain the 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline. The method has the advantages of mild reaction conditions, short reaction time, simple post-treatment operation, low-cost and easily-obtained reagents, high purity, high yield and low cost, and is suitable for industrial production.
Description
Technical Field
The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline.
Background
Imidazolyl urea (imidocarb), chemical name N, N' -bis [3- (4, 5-dihydro-1H-imidazol-2-yl) phenyl ] urea, developed by monbijoustass, switzerland, its dihydrochloride or dipropionate, is used for the treatment of piridosis. The veterinary drug has the advantages of broad spectrum, low toxicity, wide application range, long action time and small dosage, has good treatment effect and good prevention effect on livestock pirosis, plasmacytosis, eperythrozoonosis of pigs and dogs and the like. The structural formula is as follows:
with the wide spread of piroplasmosis around the world, the demand for such drugs is increasing. In face of urgent demands for the medicine at home and abroad, a method suitable for industrial production is sought, an economic and reasonable process route is sought, and the preparation method has important economic and social benefits for filling up domestic blank, promoting development of veterinary medicine industry and meeting domestic and overseas demands.
The current synthesis route of the imidazole phenylurea takes m-nitrobenzonitrile as an initial raw material, and the target compound (imidazole phenylurea) is obtained through three steps of cyclization, reduction and condensation. The reaction equation is as follows:
the catalyst sulfur is needed in the preparation process of the imidazole phenylurea intermediate 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline, but the sulfur is a national control chemical and is not easy to purchase; meanwhile, the reaction time is up to 24 hours, the raw materials remain 5 percent, the purity of the obtained 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is low, the yield is low, the solvent consumption is large (10 times of the solvent consumption), the post-treatment is complicated (filtration after cooling is needed, and then reduced pressure distillation is carried out), and the yield, the yield and the purity of the subsequent 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline are influenced. Therefore, a method which has mild reaction conditions, short reaction time, simple post-treatment operation, low-cost and easily available reagents, high purity, high yield and low cost and is suitable for industrial production of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is needed.
Disclosure of Invention
The application aims to provide a preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline. The method has the advantages of mild reaction conditions, short reaction time, simple post-treatment operation, low-cost and easily-obtained reagents, high purity, high yield and low cost, and is suitable for industrial production.
In order to achieve the above purpose, the application adopts the following technical scheme:
the application provides a preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline, which comprises the following steps:
dissolving m-nitrobenzaldehyde, ethylenediamine and trimethylchlorosilane in an aprotic solvent, heating under the protection of nitrogen, reacting, cooling to room temperature after the reaction is finished, adding water to separate out solid, and filtering to obtain the 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline.
Preferably, the aprotic solvent is selected from dioxane, dimethyl sulfoxide, N-dimethylformamide or N, N-dimethylacetamide.
Preferably, the aprotic solvent is N, N-dimethylformamide.
Preferably, the temperature of the reaction is 60-110 ℃, and the reaction time is 6-8h.
More preferably, the reaction is to raise the temperature to 60-89 ℃, react for 3-5 hours, then continue raising the temperature to 90-110 ℃ and react for 1-3 hours.
Preferably, the molar ratio of the m-nitrobenzaldehyde to the ethylenediamine is 1 (1-3).
Preferably, the molar ratio of the m-nitrobenzaldehyde to the ethylenediamine is 1:1.2.
Preferably, the volume ratio of the m-nitrobenzaldehyde to the aprotic solvent is 1 (1-5).
Preferably, the volume ratio of the m-nitrobenzaldehyde to the aprotic solvent is 1:2.
Preferably, the molar ratio of the m-nitrobenzaldehyde to the trimethylchlorosilane is 1 (0.05-5).
Preferably, the molar ratio of the m-nitrobenzaldehyde to the trimethylchlorosilane is 1:0.1.
The application has the beneficial effects that:
(1) The application solves the problem that the 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline intermediate of the imidazole phenylurea cannot be crystallized in common solvents (such as methanol, ethanol and the like).
(2) The application solves the problems of long reaction time, large solvent consumption, difficult purchase of catalyst, low yield and the like when the 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is cyclized.
(3) The method has the advantages of mild cyclization reaction conditions, short reaction time, simple post-treatment operation, low-cost and easily-obtained used reagents, high purity, high yield, lower cost and small environmental pollution, and is suitable for industrial production.
Drawings
Fig. 1: CD for the product obtained in example 1 3 In OD 1 H-NMR spectrum.
Fig. 2: CD for the product obtained in example 1 3 In OD 13 C-NMR spectrum.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
As described in the background art, 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is an intermediate for producing mizophenylurea, and is generally prepared by reacting m-nitrobenzonitrile and ethylenediamine as raw materials, sulfur as a catalyst and alcohols (methanol or ethanol) as solvents. However, sulfur is a national control chemical and is not easy to purchase; meanwhile, the reaction time is long, the utilization rate of raw materials is required to be improved, the purity of the obtained 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is low, the yield is low, the solvent consumption is large (10 times of the solvent consumption), and the post-treatment is complicated (filtration after cooling is needed and then reduced pressure distillation is needed).
Based on the above, the application provides a preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline. M-nitrobenzaldehyde and ethylenediamine are used as reaction raw materials, trimethylchlorosilane is used as a catalyst, and N, N-dimethylformamide is used as a solvent to prepare 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline. The preparation method has the advantages of short reaction time, less solvent consumption, easily obtained raw materials, mild reaction, easy precipitation of the product in aprotic solvents, and great improvement of yield and purity.
The reaction route of the application is as follows:
in order to enable those skilled in the art to more clearly understand the technical scheme of the present application, the technical scheme of the present application will be described in detail with reference to specific embodiments.
The test materials used in the examples of the present application are all conventional in the art and are commercially available.
Example 1
30.2g of m-nitrobenzaldehyde, 18g of ethylenediamine and 2.2g of trimethylchlorosilane are dissolved in 90ml of N, N-dimethylformamide, nitrogen is introduced for protection, stirring is carried out, the temperature is raised to 80 ℃, the reaction is maintained for 4 hours, then the temperature is raised to 100 ℃, the reaction is continued for 2 hours, and after the reaction is completed, the solution is cooled to 25 ℃; 270ml of water is slowly added dropwise, the solid is slowly precipitated, stirring is continued for 1h, filtering and drying are carried out, and 36.6g of yellow powdery solid is obtained, namely 2- (3-nitrophenyl) imidazoline, with the yield of 95.6% and the purity of 98.4%. The hydrogen and carbon spectra of this product are shown in figures 1 and 2.
Example 2
30.2g of m-nitrobenzaldehyde, 18g of ethylenediamine and 1.1g of trimethylchlorosilane are dissolved in 90ml of N, N-dimethylformamide, nitrogen is introduced for protection, stirring is carried out, the temperature is raised to 80 ℃, the reaction is maintained for 4 hours, then the temperature is raised to 100 ℃, the reaction is continued for 2 hours, and after the reaction is completed, the solution is cooled to 25 ℃; 270ml of water is slowly added dropwise, the solid is slowly precipitated, stirring is continued for 1h, filtering and drying are carried out, and 36.3g of yellow powdery solid is obtained, namely 2- (3-nitrophenyl) imidazoline, with the yield of 95.0% and the purity of 96.6%.
Example 3
30.2g of m-nitrobenzaldehyde, 14.4g of ethylenediamine and 2.2g of trimethylchlorosilane are dissolved in 60ml of N, N-dimethylformamide, nitrogen is introduced for protection, stirring is carried out, the temperature is raised to 80 ℃, the reaction is maintained for 4 hours, then the temperature is raised to 100 ℃, the reaction is continued for 2 hours, and after the reaction is completed, the solution is cooled to 25 ℃; 180ml of water is slowly added dropwise, the solid is slowly precipitated, stirring is continued for 1h, and the yellow powdery solid is obtained by filtering, namely, 37.2g of 2- (3-nitrophenyl) imidazoline, the yield is 97.4%, and the purity is 98.1%.
Example 4
30.2g of m-nitrobenzaldehyde, 14.4g of ethylenediamine and 2.2g of trimethylchlorosilane are dissolved in 60ml of N, N-dimethylacetamide, nitrogen is introduced for protection, stirring is carried out, the temperature is raised to 70 ℃, the reaction is maintained for 4 hours, then the temperature is raised to 110 ℃, the reaction is continued for 2 hours, and after the reaction is completed, the solution is cooled to 25 ℃; 180ml of water is slowly added dropwise, the solid is slowly precipitated, stirring is continued for 1h, and 36.8g of yellow powdery solid is obtained by filtering, namely 2- (3-nitrophenyl) imidazoline, the yield is 96.3%, and the purity is 97.8%.
Comparative example 1
29.6g of m-nitrobenzonitrile, 14.4g of ethylenediamine and 3.3g of sulfur are dissolved in 300ml of methanol, stirred and heated to reflux, and the reflux reaction is maintained for 24 hours; after the reaction is completed, the solution is cooled to 25 ℃; filtering, distilling the filtrate at normal pressure, recovering 210ml of methanol, cooling the mother liquor to 15 ℃ to slowly precipitate solid, and maintaining stirring for 1h; filtration gave 34.5g of a yellow powdered solid, i.e., 2- (3-nitrophenyl) imidazoline, in 90.3% yield and 91.3% purity.
Comparative example 2
29.6g of m-nitrobenzonitrile, 14.4g of ethylenediamine and 3.3g of sulfur are dissolved in 300ml of ethanol, stirred and heated to reflux, and the reflux reaction is maintained for 21 hours; after the reaction is finished, cooling the solution to 25 ℃, filtering, distilling the filtrate at normal pressure, recovering 200ml of ethanol, cooling the mother solution to 15 ℃ and slowly separating out solids, and keeping stirring for 1h; filtration gave 34.2g of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline as a yellow powdery solid in 89.5% yield and 92.5% purity.
Test examples
The yields and purities of 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline prepared in examples 1 to 4 and comparative examples 1 to 2 were compared to each other under the same conditions to prepare 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline, and the results are shown in Table 1.
The method for preparing the 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline by adopting the same conditions comprises the following steps: 45g of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline is added into 230ml of n-butanol, 3.8g of ferric trichloride and 4.5g of active carbon are added, the temperature is continuously raised to 75 ℃, 23g of 80% hydrazine hydrate solution is slowly added dropwise under the stirring state, the temperature is controlled at 75-85 ℃, and the reaction is continuously maintained at 75-85 ℃ for 2 hours after the dropwise addition is completed; after the reaction is finished, the mother liquor is cooled to 5-10 ℃ after hot filtration, stirring is continued for 1H, and the light yellow powdery solid is obtained after filtration, namely the 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline.
TABLE 1
| Project | Yield% | Purity% |
| Example 1 | 90.7 | 98.5 |
| Example 2 | 89.5 | 97.4 |
| Example 3 | 92.3 | 98.3 |
| Example 4 | 91.6 | 97.8 |
| Comparative example 1 | 81.7 | 93.3 |
| Comparative example 2 | 82.3 | 94.2 |
Comparative examples 1 to 2- (3-nitrophenyl) imidazoline was prepared by conventional methods, and it can be seen from a comparison of examples 1 to 4 and comparative examples 1 to 2 that the preparation time of examples was generally 5 to 8 hours, whereas the preparation time of comparative examples required at least 21 hours. Therefore, the preparation method can greatly shorten the preparation time of the 2- (3-nitrophenyl) imidazoline, improve the yield from 90.3% to 97.4%, fully convert the raw materials into products, accord with conservation of materials, and improve the purity from 91.3% to 98.4%. As can be seen from Table 1, the 2- (3-nitrophenyl) imidazoline prepared by the method of the present application was higher in purity and higher in yield in the subsequent preparation of 2- (3-aminophenyl) -4, 5-dihydro-1H-imidazoline.
The above description is only of the preferred embodiments of the present application and is not intended to limit the present application, but various modifications and variations can be made to the present application by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims (10)
1. A method for preparing 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline, which is characterized by comprising the following steps:
dissolving m-nitrobenzaldehyde, ethylenediamine and trimethylchlorosilane in an aprotic solvent, heating under the protection of nitrogen, reacting, cooling to room temperature after the reaction is finished, adding water to separate out solid, and filtering to obtain the 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline.
2. The method of claim 1, wherein the aprotic solvent is selected from dioxane, dimethyl sulfoxide, N-dimethylformamide or N, N-dimethylacetamide.
3. The method of claim 2, wherein the aprotic solvent is N, N-dimethylformamide.
4. The preparation method according to claim 1, wherein the reaction temperature is 60-110 ℃ and the reaction time is 6-8h.
5. The method according to claim 1, wherein the molar ratio of m-nitrobenzaldehyde to ethylenediamine is 1 (1-3).
6. The method according to claim 5, wherein the molar ratio of m-nitrobenzaldehyde to ethylenediamine is 1:1.2.
7. The preparation method according to claim 1, wherein the volume ratio of the m-nitrobenzaldehyde to the aprotic solvent is 1 (1-5).
8. The method according to claim 7, wherein the volume ratio of m-nitrobenzaldehyde to aprotic solvent is 1:2.
9. The preparation method according to claim 1, wherein the molar ratio of m-nitrobenzaldehyde to trimethylchlorosilane is 1 (0.05-5).
10. The method according to claim 9, wherein the molar ratio of m-nitrobenzaldehyde to trimethylchlorosilane is 1:0.1.
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| CN202210125419.4A CN116621781A (en) | 2022-02-10 | 2022-02-10 | Preparation method of 2- (3-nitrophenyl) -4, 5-dihydro-1H-imidazoline |
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2022
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