CN117247354A - Preparation method of topramezone metabolite T319 - Google Patents
Preparation method of topramezone metabolite T319 Download PDFInfo
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- CN117247354A CN117247354A CN202311233732.0A CN202311233732A CN117247354A CN 117247354 A CN117247354 A CN 117247354A CN 202311233732 A CN202311233732 A CN 202311233732A CN 117247354 A CN117247354 A CN 117247354A
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- topramezone
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- IYMLUHWAJFXAQP-UHFFFAOYSA-N topramezone Chemical class CC1=C(C(=O)C2=C(N(C)N=C2)O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 IYMLUHWAJFXAQP-UHFFFAOYSA-N 0.000 title claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 17
- 230000008569 process Effects 0.000 claims abstract description 12
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 239000012074 organic phase Substances 0.000 claims description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- OIXUJRCCNNHWFI-UHFFFAOYSA-N 1,2-dioxane Chemical compound C1CCOOC1 OIXUJRCCNNHWFI-UHFFFAOYSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000012071 phase Substances 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 238000010025 steaming Methods 0.000 claims description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 abstract description 7
- 239000000575 pesticide Substances 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 7
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- BPPVUXSMLBXYGG-UHFFFAOYSA-N 4-[3-(4,5-dihydro-1,2-oxazol-3-yl)-2-methyl-4-methylsulfonylbenzoyl]-2-methyl-1h-pyrazol-3-one Chemical class CC1=C(C(=O)C=2C(N(C)NC=2)=O)C=CC(S(C)(=O)=O)=C1C1=NOCC1 BPPVUXSMLBXYGG-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- -1 iron ions Chemical class 0.000 description 6
- 241000196324 Embryophyta Species 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- IGMNYECMUMZDDF-UHFFFAOYSA-N homogentisic acid Chemical compound OC(=O)CC1=CC(O)=CC=C1O IGMNYECMUMZDDF-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000003405 preventing effect Effects 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 2
- ZHLWCBHWYUISFY-UHFFFAOYSA-N Hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)C(O)C1=CC=CC=C1 ZHLWCBHWYUISFY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 244000036975 Ambrosia artemisiifolia Species 0.000 description 1
- 235000003129 Ambrosia artemisiifolia var elatior Nutrition 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- 241000219312 Chenopodium Species 0.000 description 1
- 241001091551 Clio Species 0.000 description 1
- 241000234653 Cyperus Species 0.000 description 1
- 244000058871 Echinochloa crus-galli Species 0.000 description 1
- 206010024796 Logorrhoea Diseases 0.000 description 1
- 241000195947 Lycopodium Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 244000042664 Matricaria chamomilla Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- FKUYMLZIRPABFK-UHFFFAOYSA-N Plastoquinone 9 Natural products CC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCCC(C)=CCC1=CC(=O)C(C)=C(C)C1=O FKUYMLZIRPABFK-UHFFFAOYSA-N 0.000 description 1
- 235000010086 Setaria viridis var. viridis Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 235000003484 annual ragweed Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 235000006263 bur ragweed Nutrition 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000003763 chloroplast Anatomy 0.000 description 1
- 235000003488 common ragweed Nutrition 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 244000230342 green foxtail Species 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000447 pesticide residue Substances 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- FKUYMLZIRPABFK-IQSNHBBHSA-N plastoquinone-9 Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC\C(C)=C\CC1=CC(=O)C(C)=C(C)C1=O FKUYMLZIRPABFK-IQSNHBBHSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 235000009736 ragweed Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 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
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
Abstract
The invention relates to a preparation method of topramezone metabolite T319, belonging to the technical field of pesticides. The preparation method is that the compound of formula I reacts with liquid alkali to generate the compound of formula II, and then the compound of formula III is separated and purified to generate the compound of formula IV. The preparation method has the advantages of easily available raw materials and no need of using extremely toxic raw materials. The method has the advantages of simple steps, convenient operation, controllable experimental process, no need of harsh reaction environment, mild conditions and easy realization of the process, realizes the mass preparation of the topramezone metabolite, and can fully meet the sample quantity requirement of pesticide registration.
Description
Technical Field
The invention relates to the technical field of pesticides, in particular to a preparation method of topramezone metabolite T319.
Background
Topramezone (Topramezone) is a novel pyrazolone post-emergence foliar treatment herbicide developed by basf, european company under the trade name of many such as Convey, impact, clio, bract, etc. Topramezone is mainly used for controlling corn field weeds, such as broadleaf weeds and grassy weeds. Meanwhile, topramezone is used as a compound with broad-spectrum biological activity and has excellent preventing and killing effects on various weeds, such as heterocyperus, green bristlegrass, barnyard grass, garrulous cyperus, lycopodium, ragweed, chamomile, chenopodium and the like. The action mechanism of the topramezone is that the topramezone is bonded with iron ions in an HPPD active center to form a complex, so that the complex loses catalytic effect, thereby effectively preventing the biosynthesis process of converting hydroxyphenylpyruvic acid (HPP) into Homogentisate (HGA), further effectively inhibiting the synthesis of plastoquinone and tocopherol, indirectly preventing the synthesis of carotenoid and photosynthesis of chloroplast, and finally leading to albino death of weeds. Topramezone has high safety to corn and low toxicity to mammals. Can be degraded into non-toxic products under high temperature and ultraviolet light, so that the problem of pesticide residue in the environment is not worried after the pesticide is applied. Has good market prospect. At present, pesticide registration is one of the important works of enterprises, and the pesticide enterprises are the most effective way to obtain the development foundation and the core competitiveness. Thus, the preparation of large quantities of topramezone metabolites for toxicological test studies is also a major issue for numerous researchers.
The chemical name of the topramezone metabolite T319 is 4- [ 2-methyl-3-cyano-4-methylsulfonyl ] -1-methyl-5-hydroxy-1H-pyrazole, cyano is required to be introduced, cyanide is taken as a raw material in the current main route, substitution reaction on benzene rings occurs, the synthetic route is complex, and the used drugs are dangerous and have high toxicity, so that the topramezone metabolite T319 is not suitable for mass preparation.
Disclosure of Invention
Aiming at the problems that the existing synthesis method of the topramezone metabolite T319 has large toxicity of raw materials, cannot be used for preparing a large amount and the like, the invention provides a preparation method of the topramezone metabolite T319, so as to solve the problems. The invention adopts oxime compounds as the initial raw materials, avoids the use of highly toxic cyanide and is easy to realize.
The technical scheme of the invention is as follows:
a preparation method of topramezone metabolite T319, the reaction formula is as follows:
；
reacting the compound shown in the formula I with liquid alkali to generate a compound shown in the formula II, separating and purifying the compound shown in the formula III to generate a compound shown in the formula IV;
the specific method comprises the following steps:
(1) Dissolving a compound shown in a formula I in an organic solvent I, adding alkali, heating to 20-70 ℃, and carrying out heat preservation reaction for 1-8 hours; separating the solution after the reaction is finished, extracting the water phase once by using an organic solvent, and merging the organic phases; washing the organic phase with hydrochloric acid and water in sequence, then steaming to remove the solvent, and adding methanol for crystallization; filtering and refining with methanol to obtain compound of formula II;
(2) Adding an organic solvent II and an acid binding agent into the compound of the formula II and the compound of the formula III prepared in the step (1), uniformly stirring, adding a condensing agent, heating to 10-80 ℃, and preserving heat; and (3) adding water for washing after the reaction is finished, concentrating an organic phase, and adding methanol for crystallization to obtain the compound shown in the formula IV.
Further, in the step (1), the organic solvent I is at least one of 1, 2-dichloroethane, toluene or benzene.
Further, the amount of the first organic solvent is 2-5 g/g based on the compound of the formula I.
In the step (1), the alkali is at least one of sodium methoxide, sodium ethoxide, potassium carbonate, triethylamine, pyridine and sodium hydroxide.
Further, in the step (1), the amount of the base to be used is 0.5 to 3mol/mol, preferably 0.5 to 2mol/mol, based on the compound of the formula I.
Further, in the step (2), the compound of formula III is used in an amount of 1.1 to 1.5mol/mol based on the compound of formula II.
Further, in the step (2), the condensing agent is at least one of sulfonyl chloride, methylsulfonyl chloride, thionyl chloride and N, N' -carbonyldiimidazole.
Further, in the step (2), the organic solvent II is at least one of benzene, toluene, acetonitrile, tetrahydrofuran, 1, 2-dichloroethane and 1, 2-dioxane.
In the step (2), the amount of the second organic solvent is 2-4 g/g based on the compound of the formula II.
Further, in the step (2), the acid binding agent is at least one of sodium methoxide, sodium ethoxide, potassium carbonate, triethylamine and pyridine.
In the step (2), the condensing agent is used in an amount of 1 to 3mol/mol based on the compound of the formula II.
The invention has the beneficial effects that:
the preparation method of the topramezone metabolite T319 provided by the invention can finally obtain the product with the purity of more than or equal to 97.5%. The preparation method has the advantages of easily available raw materials and no need of using extremely toxic raw materials. The method has the advantages of simple steps, convenient operation, controllable experimental process, no need of harsh reaction environment, mild conditions and easy realization of the process, realizes the mass preparation of the topramezone metabolite, and can fully meet the sample quantity requirement of pesticide registration.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the description of the embodiments or the prior art will be briefly described below, and it will be obvious to those skilled in the art that other drawings can be obtained from these drawings without inventive effort.
FIG. 1 is a compound of formula IV according to example 1 of the present invention 1 HNMR profile.
FIG. 2 is a schematic illustration of a compound of formula IV according to example 1 of the present invention 13 CNMR profile.
FIG. 3 is an HPLC plot of a compound of formula IV of example 1 of the present invention.
Detailed Description
In order to make the technical solution of the present invention better understood by those skilled in the art, the technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the present invention without making any inventive effort, shall fall within the scope of the present invention.
Example 1
The preparation method of the topramezone metabolite T319 comprises the following steps:
(1) 50g (0.19 mol) of a compound of the formula I are dissolved in 100g of 1, 2-dichloroethane, 15g (0.11 mol) of a 30% strength liquid base are added, heated to 65℃and incubated for 4h; separating liquid after the reaction is finished, wherein the upper layer is an organic phase. As can be seen from the observation of the experimental phenomenon and the detection result of TLC analysis, the sodium carboxylate product generated by the reaction is mainly dissolved in the organic phase, and the analysis causes mainly include the following points: 1. the water quantity of the reaction system is less, so that the solubility of sodium carboxylate is reduced; 2. the alkali amount in the water is more, so that the solubility of sodium carboxylate is further reduced; 3. the sodium carboxylate prepared by the invention is different from sodium benzoate, and other hydrophobic groups are contained on the benzene ring, so that the water solubility of the whole structure is affected. The organic phase is washed once with 70g of water and once with 50g of 1, 2-dichloroethane, and the organic phases are combined; the organic phase was washed twice with 100g of 10% aqueous hydrochloric acid, twice with 100g of water, then the organic phase was concentrated under reduced pressure until no fraction was obtained, and a small amount of methanol was added for dispersion, and the mixture was left overnight to precipitate a solid, which was suction-filtered, washed with a small amount of methanol and dried to give 42.55g of a pink solid (compound of formula II) having a content of 97.2% and a yield of 90.8%.
(2) Taking 40g (0.16 mol) of the compound of the formula II and 17.9g (0.18 mol) of the compound of the formula III prepared in the step (1), adding 100g of 1, 2-dichloroethane and 55.3g (0.40 mol) of potassium carbonate, uniformly stirring, then dropwise adding 22.0g (0.19 mol) of methylsulfonyl chloride, controlling the temperature to be 50 ℃, and keeping the temperature for 1h after dropwise adding; after the reaction is finished, 100g of water is respectively added for three times, then the mixture is concentrated under negative pressure to be nearly dry, 100g of methanol is added for cooling and precipitation, suction filtration and a small amount of methanol washing are carried out, and 45.9g of yellow solid (compound of formula IV) with the content of 97.8 percent and the yield of 88.2 percent is obtained.
The HNMR, CNMR and HPLC patterns of the compound shown in the formula IV are shown in figures 1-3.
1 H NMR (500 MHz，Chloroform-d) δ 8.05(d，J = 8.0 Hz，1H)，7.85(d，J = 8.0 Hz，1H)，7.42(s，1H)，3.54(s，3H)，3.42(s，3H)，2.51(s，3H)。
13 C NMR (500 MHz，Chloroform-d) δ 186.42，155.07，145.24，142.81，141.90，139.90，131.20，126.91，114.43，111.15，104.89，42.78，32.96，17.99。
HPLC detection data are shown in Table 1 below.
TABLE 1 HPLC detection results for Compounds of formula IV
Example 2
The preparation method of the topramezone metabolite T319 comprises the following steps:
(1) 50g (0.19 mol) of a compound of the formula I are dissolved in 150g of toluene, 65.8g (0.14 mol) of a 30% aqueous potassium carbonate solution are added, and the mixture is heated to 70℃and incubated for 6h; separating liquid after the reaction is finished, wherein the upper layer is an organic phase, and washing the organic phase once with 100g of water; the organic phase was washed twice with 100g of 10% aqueous hydrochloric acid, twice with 100g of water, then the organic phase was concentrated under reduced pressure to give about 1/3 of the solvent, which was left overnight to precipitate a solid, which was suction filtered, washed with a small amount of methanol, and dried to give 43.61g of a pink solid (compound of formula II) with a content of 96.1% and a yield of 92.0%.
(2) Taking 40g (0.16 mol) of the compound shown in the formula II and 24.0g (0.24 mol) of the compound shown in the formula III prepared in the step (1), adding 112g of toluene and 35.6g (0.35 mol) of triethylamine, uniformly stirring, then dropwise adding 29.1g (0.24 mol) of thionyl chloride, controlling the temperature to be 30 ℃, and keeping the temperature for 1.5 hours after the dropwise adding is finished; after the reaction is finished, 100g of water is respectively added for three times, then the mixture is concentrated under negative pressure to be nearly dry, 100g of methanol is added for cooling and precipitation, suction filtration and a small amount of methanol washing are carried out, and 44.2g of yellow solid (compound of formula IV) with the content of 97.7 percent and the yield of 84.5 percent is obtained.
Example 3
The preparation method of the topramezone metabolite T319 comprises the following steps:
(1) 50g (0.19 mol) of a compound of the formula I are dissolved in 100g of 1, 2-dichloroethane, 22.7g (0.17 mol) of a 30% strength liquid base are added, heated to 40℃and incubated for 4h; separating liquid after the reaction is finished, wherein the upper layer is an organic phase, 70g of the organic phase is washed once by water, 50g of the aqueous phase is washed once by 1, 2-dichloroethane, and the organic phases are combined; the organic phase is washed twice with 100g of 10% hydrochloric acid aqueous solution and twice with 100g of water, then the organic phase is concentrated under reduced pressure until no fraction is produced, a small amount of methanol is added for dispersion, the mixture is left overnight to precipitate solid, the solid is filtered off with suction, the mixture is washed with a small amount of methanol, 43.90g of pink solid (compound of formula II) is obtained after drying, the content is 98.1%, and the yield is 94.7%.
(2) Taking 40g (0.16 mol) of the compound of the formula II prepared in the step (1), 120g acetonitrile, 47.0g (0.29 mol) of N, N' -carbonyldiimidazole and 16.6g (0.21 mol) of pyridine, uniformly stirring, then dropwise adding 22.02g (0.22 mol) of the compound of the formula III into the mixture after 40g of acetonitrile is dissolved, controlling the temperature to be 20 ℃, and preserving the heat for 4 hours after the dropwise adding is finished; concentrating under negative pressure until the mixture is nearly dry, adding 50g of methanol and 50g of water respectively, adding a small amount of hydrochloric acid to regulate the pH to be less than 2, cooling and crystallizing to separate out to obtain 40.5g of yellow solid (compound of formula IV) with the content of 97.0% and the yield of 76.9%.
Although the present invention has been described in detail by way of preferred embodiments with reference to the accompanying drawings, the present invention is not limited thereto. Various equivalent modifications and substitutions may be made in the embodiments of the present invention by those skilled in the art without departing from the spirit and scope of the present invention, and it is intended that all such modifications and substitutions be within the scope of the present invention/be within the scope of the present invention as defined by the appended claims.
Claims (10)
1. A preparation method of topramezone metabolite T319, which is characterized by comprising the following reaction formula:
；
the specific method comprises the following steps:
(1) Dissolving a compound shown in a formula I in an organic solvent I, adding alkali, heating to 20-70 ℃, and carrying out heat preservation reaction for 1-8 hours; separating the solution after the reaction is finished, extracting the water phase once by using an organic solvent, and merging the organic phases; washing the organic phase with hydrochloric acid and water in sequence, then steaming to remove the solvent, and adding methanol for crystallization; filtering and refining with methanol to obtain compound of formula II;
(2) Adding an organic solvent II and an acid binding agent into the compound of the formula II and the compound of the formula III prepared in the step (1), uniformly stirring, adding a condensing agent, heating to 10-80 ℃, and preserving heat; and (3) adding water for washing after the reaction is finished, concentrating an organic phase, and adding methanol for crystallization to obtain the compound shown in the formula IV.
2. The process according to claim 1, wherein in the step (1), the organic solvent I is at least one of 1, 2-dichloroethane, toluene and benzene.
3. The method according to claim 1, wherein in the step (1), the base is at least one of sodium methoxide, sodium ethoxide, potassium carbonate, triethylamine, pyridine and sodium hydroxide.
4. The process according to claim 1, wherein in step (1), the amount of the base is 0.5 to 3mol/mol based on the compound of formula I.
5. The process according to claim 1, wherein in step (2), the compound of formula III is used in an amount of 1.1 to 1.5mol/mol based on the compound of formula II.
6. The process according to claim 1, wherein in the step (2), the organic solvent II is at least one of benzene, toluene, acetonitrile, tetrahydrofuran, 1, 2-dichloroethane, and 1, 2-dioxane.
7. The process according to claim 1, wherein in step (2), the amount of the second organic solvent is 2 to 4g/g based on the compound of formula II.
8. The method according to claim 1, wherein in the step (2), the acid-binding agent is at least one of sodium methoxide, sodium ethoxide, potassium carbonate, triethylamine, and pyridine.
9. The process according to claim 1, wherein in the step (2), the condensing agent is at least one of sulfonyl chloride, methylsulfonyl chloride, thionyl chloride, and N, N' -carbonyldiimidazole.
10. The process according to claim 1, wherein in step (2), the condensing agent is used in an amount of 1 to 3mol/mol based on the compound of the formula II.
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