CN116375656A - Metconazole metabolite and preparation method thereof - Google Patents
Metconazole metabolite and preparation method thereof Download PDFInfo
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- CN116375656A CN116375656A CN202111594434.5A CN202111594434A CN116375656A CN 116375656 A CN116375656 A CN 116375656A CN 202111594434 A CN202111594434 A CN 202111594434A CN 116375656 A CN116375656 A CN 116375656A
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- metconazole
- metabolite
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- solvent
- oxidant
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- XWPZUHJBOLQNMN-UHFFFAOYSA-N metconazole Chemical class C1=NC=NN1CC1(O)C(C)(C)CCC1CC1=CC=C(Cl)C=C1 XWPZUHJBOLQNMN-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000007800 oxidant agent Substances 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000011259 mixed solution Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- 239000005868 Metconazole Substances 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 6
- 239000012362 glacial acetic acid Substances 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 229940117975 chromium trioxide Drugs 0.000 claims description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical group [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 238000000926 separation method Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 17
- 241000282414 Homo sapiens Species 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 5
- 239000000575 pesticide Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000011343 solid material Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241000223600 Alternaria Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001661277 Moelleriella libera Species 0.000 description 1
- 241000221300 Puccinia Species 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of compounds, and relates to a metconazole metabolite and a preparation method thereof. The metconazole metabolite is shown in formula I, and is dissolved in a solvent at 0-20 ℃, and oxidant is added into the mixed solution for reaction for 1-3 hours, so as to obtain the metconazole metabolite. The preparation method provided by the invention has a simple process and is suitable for mass production in laboratories. The product of the invention has high yield, the purity is 99% after separation and purification, and the cost is low.
Description
Technical Field
The invention belongs to the field of compounds, and relates to a metconazole metabolite and a preparation method thereof.
Background
Metconazole is also called as hydroxymyclobutanil, and is a novel broad-spectrum systemic bactericide. Has excellent protection and treatment effects, low toxicity to non-target organisms, low dosage and high bactericidal activity, meets the green prevention and control requirements, and has good environmental prospect. The application of the leaf bacteria in the field has excellent effect on the plant diseases of the cereal crops of the aschersonia aleyrodis, the alternaria and the puccinia. More than 20 kinds of metconazole metabolites can be detected in animals and plants. The metabolite of metconazole is mainly used for researching the toxicity of pesticides on animals and plants. When metconazole is used for spraying pesticides on plants, agricultural products can be eaten by human beings or animals, and when the metconazole enters the human beings or animals, the metconazole pesticides can generate metabolism in the human beings, so that the synthesis of the metconazole metabolites is also important for the human beings to study the residual condition of the metconazole metabolites in animals and plants in order to study the harm of the metabolites to the human beings and the animals. In order to meet the scientific research demands, a large amount of metconazole metabolites need to be prepared, and a simple and efficient method needs to be provided.
Disclosure of Invention
The invention aims to provide a metconazole metabolite and a preparation method thereof.
In order to achieve the above purpose, the invention adopts the technical scheme that:
a metconazole metabolite, characterized in that: the metconazole metabolite is represented by formula one below:
the preparation method of metconazole metabolite has the following reaction formula:
and (3) adding metconazole into a solvent for dissolution at the temperature of 0-20 ℃, and adding an oxidant into the mixed solution for reaction for 1-3 hours to obtain metconazole metabolite.
The preferred reaction system temperature is 7-15 ℃.
The mole ratio of the metconazole to the oxidant to the solvent is 1:2-20:10-40.
The solvent is one or more of ethanol, methanol, ethyl acetate, glacial acetic acid, hydrochloric acid or sulfuric acid;
the oxidant is chromium trioxide.
Washing the product with water, repeatedly extracting with an organic solvent, combining organic layers, and then drying, desolventizing and recrystallizing to obtain the metconazole metabolite.
The organic solvent is one or more of DMF, methanol, ethyl acetate, dichloromethane, tetrahydrofuran, n-hexane or petroleum ether.
The recrystallization is to mix the dried product with a mixed solvent of normal hexane and ethyl acetate for recrystallization, wherein the volume ratio of the normal hexane to the ethyl acetate is 3:4.
The metconazole metabolite is used for evaluating the safety of metconazole, when the metconazole is used for spraying pesticides on plants, agricultural products can be eaten by human beings or animals, when the metconazole enters the human beings or animals, the metconazole pesticides can generate metabolism in the human bodies, and in order to study the harm of the metconazole metabolite to the human beings and the animals, the metconazole metabolite needs to be subjected to a toxicological experiment for the use of the metconazole.
The invention has the following advantages and positive effects:
(1) The preparation method provided by the invention has a simple process and is suitable for mass production in laboratories.
(2) The product of the invention has high yield, the purity is 99% after separation and purification, and the cost is low.
(3) The synthesis method has simple and clear synthesis steps and convenient and easily obtained raw materials.
(4) The purification step can be directly carried out by adopting recrystallization, the operation step is simple, and the high-purity product can be obtained by rapid and high-efficiency purification.
(5) The reagents involved in the experiment are all conventional solvents, are simple and easy to obtain, have low price, and can help to reduce the production cost.
(6) The product can be prepared in a large quantity, has low cost and provides support for scientific research.
Drawings
FIG. 1 is a High Performance Liquid Chromatography (HPLC) diagram of the product of example 1 of the present invention.
FIG. 2 is a 1H-NMR chart of the product of example 1 according to the invention.
FIG. 3 is a Mass spectrum (Mass) of the product of example 1 of the present invention.
FIG. 4 is a High Performance Liquid Chromatography (HPLC) diagram of comparative example 1 of the present invention.
FIG. 5 is a High Performance Liquid Chromatography (HPLC) diagram of comparative example 2 of the present invention.
Detailed Description
The invention is further illustrated below in connection with specific examples, which should not be construed as limiting the invention.
Example 1
Adding metconazole (16.0 g,0.05 mol) as raw material into a three-neck round bottom flask equipped with a stirrer, a condenser and a thermometer, adding 50mL of glacial acetic acid (analytically pure, mass fraction 99.5%, density 1.05), stirring, controlling the temperature at 10deg.C, adding CrO 3 (20 g,0.2 mol) was slowly added to the reaction solution, and after the completion of the addition, the reaction was carried out at constant temperature for 2 hours, 50mL of ice water was added to the reaction solution, the product ethyl acetate was extracted three times, the organic layers were combined, and then dried over anhydrous sodium sulfate, and desolventized to obtain 10.4g of a yellow solid material.
The yellow solid material was ethyl acetate: n-hexane=4: 3 to obtain 9.0g of yellow solid product with the yield of 95% and the sample purity of 99%.
Example 2
Adding metconazole crude drug (12.0 g,0.03 mol) into a three-neck round bottom flask equipped with a stirrer, a condenser and a thermometer, adding 50mL glacial acetic acid, stirring, controlling the temperature at 15 ℃, adding CrO 3 (30 g,0.3 mol) was slowly added to the reaction mixture, and after completion of the addition, the mixture was allowed to react at constant temperature for 2 hours, 50mL of ice water was added to the reaction mixture, and the product was extracted with ethyl acetateThe organic layers were combined three times and then dried over anhydrous sodium sulfate, desolventized to give 10.2g of a yellow solid material.
The yellow solid material was ethyl acetate: n-hexane=4: 3 to obtain 9.0g of yellow solid product with the yield of 90% and the sample purity of 99%.
Comparative example 1
A three-necked round bottom flask equipped with a stirrer, condenser and thermometer was charged with metconazole (16.0 g,0.05 mol), 50mL of glacial acetic acid was added and stirred, the temperature was controlled at 10℃and KMnO was added 4 (63.0 g,0.2 mol) was slowly added to the reaction solution, and after the addition was completed, the reaction was carried out at constant temperature for 2 hours, 50mL of ice water was added to the reaction solution, the product ethyl acetate was extracted three times, the organic layers were combined, and then dried over anhydrous sodium sulfate, and the solvent was removed. No product was obtained by liquid chromatography.
Comparative example 2
Adding metconazole crude drug (12.0 g,0.03 mol) into a three-neck round bottom flask equipped with a stirrer, a condenser and a thermometer, adding 50mL glacial acetic acid, stirring, controlling the temperature to 30 ℃, adding CrO 3 (30 g,0.3 mol) was slowly added to the reaction solution, and after the completion of the addition, the reaction was carried out at constant temperature for 2 hours, 50mL of ice water was added to the reaction solution, the product was extracted three times with ethyl acetate, the organic layers were combined, and then dried over anhydrous sodium sulfate, and the solvent was removed. No product was obtained by liquid chromatography.
As can be seen from comparative examples 1 and 2, the invention screens the oxidant and the reaction time to obtain metconazole metabolites, and the invention selects CrO3 as the oxidant, and the product with higher yield can be obtained under the condition of the reaction temperature of 0-20 ℃.
In the foregoing, the protection scope of the present invention is not limited to the preferred embodiments of the present invention, and any simple changes or equivalent substitutions of the technical solutions that can be obviously obtained by those skilled in the art within the technical scope of the present invention disclosed in the present invention fall within the protection scope of the present invention.
Claims (7)
1. A metconazole metabolite, characterized in that: the metconazole metabolite is represented by formula one below:
2. a process for the preparation of metconazole metabolite according to claim 1, wherein: the reaction formula is as follows:
and (3) adding metconazole into a solvent for dissolution at the temperature of 0-20 ℃, and adding an oxidant into the mixed solution for reaction for 1-3 hours to obtain metconazole metabolite.
3. A process for the preparation of metconazole metabolites according to claim 2, wherein: the mole ratio of the metconazole to the oxidant to the solvent is 1:2-20:10-40.
4. A process for the preparation of metconazole metabolites according to claim 2, wherein: the solvent is one or more of ethanol, methanol, ethyl acetate, glacial acetic acid, hydrochloric acid or sulfuric acid;
the oxidant is chromium trioxide.
5. A process for the preparation of metconazole metabolites according to claim 1, wherein: washing the product with water, repeatedly extracting with an organic solvent, combining organic layers, and then drying, desolventizing and recrystallizing to obtain the metconazole metabolite.
6. The method for preparing metconazole metabolite according to claim 5, wherein: the organic solvent is one or more of DMF, methanol, ethyl acetate, dichloromethane, tetrahydrofuran, n-hexane or petroleum ether.
7. Use of metconazole metabolite according to claim 1, wherein: the metconazole metabolite is used for evaluating the safety of metconazole.
Priority Applications (1)
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|---|---|---|---|
| CN202111594434.5A CN116375656A (en) | 2021-12-24 | 2021-12-24 | Metconazole metabolite and preparation method thereof |
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| CN202111594434.5A CN116375656A (en) | 2021-12-24 | 2021-12-24 | Metconazole metabolite and preparation method thereof |
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| CN116375656A true CN116375656A (en) | 2023-07-04 |
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| CN202111594434.5A Pending CN116375656A (en) | 2021-12-24 | 2021-12-24 | Metconazole metabolite and preparation method thereof |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05271196A (en) * | 1992-03-24 | 1993-10-19 | Kureha Chem Ind Co Ltd | New (@(3754/24)1-hydroxy-1-phenyl) methyl)azolylmethylcyclopentanol derivative |
-
2021
- 2021-12-24 CN CN202111594434.5A patent/CN116375656A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05271196A (en) * | 1992-03-24 | 1993-10-19 | Kureha Chem Ind Co Ltd | New (@(3754/24)1-hydroxy-1-phenyl) methyl)azolylmethylcyclopentanol derivative |
Non-Patent Citations (1)
| Title |
|---|
| MA, MANLING ET AL.,: ""Photochemical Studies on Bicyclo[2.1.1]hexyl Derivatives: Chemical Behavior and Asymmetric Induction"", 《CHINESE JOURNAL OF CHEMISTRY》, vol. 32, no. 4, 4 April 2014 (2014-04-04), pages 307 - 312, XP071928790, DOI: 10.1002/cjoc.201300893 * |
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