CN115385792B - Process for the preparation of pyrazole herbicide intermediates - Google Patents
Process for the preparation of pyrazole herbicide intermediates Download PDFInfo
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- CN115385792B CN115385792B CN202110560519.5A CN202110560519A CN115385792B CN 115385792 B CN115385792 B CN 115385792B CN 202110560519 A CN202110560519 A CN 202110560519A CN 115385792 B CN115385792 B CN 115385792B
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- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000002363 herbicidal effect Effects 0.000 title claims abstract description 21
- 239000004009 herbicide Substances 0.000 title claims abstract description 21
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000000543 intermediate Substances 0.000 title abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims abstract description 19
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims abstract description 12
- 238000007259 addition reaction Methods 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 12
- 238000007069 methylation reaction Methods 0.000 claims description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 claims description 8
- 230000020477 pH reduction Effects 0.000 claims description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
- 239000002585 base Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 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 claims description 5
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims description 4
- 230000011987 methylation Effects 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 claims description 2
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 claims description 2
- WVLBCYQITXONBZ-UHFFFAOYSA-N trimethyl phosphate Chemical compound COP(=O)(OC)OC WVLBCYQITXONBZ-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000006243 chemical reaction Methods 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 9
- 229940126214 compound 3 Drugs 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000010907 mechanical stirring Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- YALJPBXSARRWTA-UHFFFAOYSA-N 1,3-dimethylpyrazole-4-carboxylic acid Chemical compound CC1=NN(C)C=C1C(O)=O YALJPBXSARRWTA-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- -1 amine compounds Chemical class 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- RBACIKXCRWGCBB-UHFFFAOYSA-N 1,2-Epoxybutane Chemical compound CCC1CO1 RBACIKXCRWGCBB-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 101100339555 Zymoseptoria tritici HPPD gene Proteins 0.000 description 2
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 2
- 125000003172 aldehyde group Chemical group 0.000 description 2
- 125000002843 carboxylic acid group Chemical group 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- UYVXZUTYZGILQG-UHFFFAOYSA-N methoxyboronic acid Chemical compound COB(O)O UYVXZUTYZGILQG-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 244000058871 Echinochloa crus-galli Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004280 Sodium formate Substances 0.000 description 1
- WXQMIXCKKFECIU-UHFFFAOYSA-N [4-[2-chloro-3-[(3,5-dimethylpyrazol-1-yl)methyl]-4-methylsulfonylbenzoyl]-2,5-dimethylpyrazol-3-yl] 1,3-dimethylpyrazole-4-carboxylate Chemical compound CN1N=C(C(=C1)C(=O)OC1=C(C(=NN1C)C)C(C1=C(C(=C(C=C1)S(=O)(=O)C)CN1N=C(C=C1C)C)Cl)=O)C WXQMIXCKKFECIU-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of a pyrazole herbicide intermediate, and in particular relates to synthesis of compounds shown in a formula (i) and a formula (ii). The preparation method of the compound shown in the formula (i) comprises the following steps: the ethyl acetoacetate and ethyl formate are subjected to addition reaction under the action of alkali. The method can obtain the pyrazole herbicide intermediates with the structures shown in the formula (i) and the formula (ii) with higher purity and yield, has the advantages of high safety, simple and convenient operation and low cost, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of a pyrazole herbicide intermediate.
Background
Triazolesulfonone, which isThe 4 th brand new HPPD inhibitor compound pushed out by heavy weight is an HPPD inhibitor herbicide which can be safely used for preventing and controlling gramineous weeds in the post-seedling stem and leaf treatment of paddy fields in the first instance of the world. Can effectively prevent and remove barnyard grass weeds which are resistant to ALS inhibitors and ACCase inhibitors in paddy fields and millennium seeds which are resistant to the ACCase inhibitors, and has important significance for improving the yield of paddy rice. Therefore, studies on synthesis of pyrazole compounds have been paid much attention.
Triazolesulfonone is generally prepared from the intermediate 1, 3-dimethylpyrazole-4-carboxylic acid. At present, the preparation methods of 1, 3-dimethylpyrazole-4-carboxylic acid are reported at home and abroad as described in the prior arts WO2003002062, CN110950770, CN102786489 and WO2018064119, and are mostly prepared by adopting the following two reaction routes:
reaction route one:
the above route adopts ethyl acetoacetate or analogues, triethyl orthoformate or methyl ester and acetic anhydride to react and then react with methyl hydrazine to close the ring, and then the triazole sulcotrione intermediate 1, 3-dimethylpyrazole-4-carboxylic acid is prepared by alkaline hydrolysis and acidification. Acetic anhydride and acetic acid which is a byproduct thereof used in the process have strong corrosiveness and are not easy to recycle, and the triethyl orthoformate (or methyl ester) has large dosage and high price, thus being not beneficial to industrialized mass production.
Reaction route two:
the above route adopts 3-bromopyrazole-4-ethyl formate, methyl iodide and methyl boric acid for methylation, and then alkaline hydrolysis and acidification are carried out to prepare the triazolesulfonone intermediate 1, 3-dimethylpyrazole-4-carboxylic acid. The methyl iodide used in the process has high price, high toxicity and low yield, and is unfavorable for industrial mass production.
Disclosure of Invention
The invention provides a preparation method of a pyrazole herbicide intermediate. The method can obtain the pyrazole herbicide intermediates with the structures shown in the formula (i) and the formula (ii) with higher purity and yield, has the advantages of high safety, simple and convenient operation and low cost, and is suitable for industrial production.
The invention provides a preparation method of a pyrazole herbicide intermediate shown in a formula (i), which comprises the following steps: performing addition reaction on ethyl acetoacetate and ethyl formate under the action of alkali to obtain a compound shown in a formula (i); wherein the structure of the compound of formula (i) is as follows:
the synthesis route of the pyrazole herbicide intermediate shown in the formula (i) is as follows:
the specific synthesis process is as follows: the methylene between two carbonyl groups of the acetoacetic ester (compound 1) forms carbanion to attack carbonyl carbon of the ethyl formate (compound 2) under alkaline condition, and one molecule of ethanol is separated, so that a compound with a structure shown in a formula i is generated.
In some embodiments of the invention, the molar ratio of acetoacetate to ethyl formate to base is 1 (1.05-1.5): 1.1-2.0.
In some embodiments of the invention, the addition reaction is carried out in the presence of an organic solvent selected from at least one of toluene, chlorobenzene, cyclohexane, dichloroethane, methanol, isopropanol, ethanol, tetrahydrofuran, propylene oxide or 1, 2-butylene oxide, preferably at least one of toluene, cyclohexane, dichloroethane, methanol or isopropanol.
In some embodiments of the invention, the base is selected from any of sodium methoxide, sodium ethoxide, triethylamine, N-diisopropylethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate, or N, N-dimethylaniline.
In some embodiments of the invention, the temperature of the addition reaction is 30-90 ℃, preferably 40-70 ℃; the time is 2 to 7 hours, preferably 3 to 5 hours.
In some embodiments of the invention, ethyl formate is added dropwise to the reaction system last. Preferably, the reaction system containing ethyl acetoacetate, organic solvent, and base is warmed to 40-50 ℃ before ethyl formate is added dropwise. Therefore, the acetoacetic ester is easier to form carbanion, which is beneficial to promoting the addition reaction and improving the product yield.
The invention also provides a preparation method of the pyrazole herbicide intermediate shown in the formula (ii), the compound shown in the formula (i) is prepared according to the method, and then cyclized with methyl hydrazine/hydrazine hydrate, and finally alkaline hydrolysis and acidification are carried out to obtain the compound shown in the formula (ii); wherein the structure of the compound of formula (ii) is as follows:
when methyl hydrazine is used as a reactant, the synthesis route of the pyrazole herbicide intermediate shown in the formula (ii) is as follows:
the specific synthesis process is as follows: the aldehyde group and carbonyl group are relatively active, and are easy to perform condensation reaction with hydrazine or amine compounds, water is removed and ring closure is carried out to obtain a compound 3, and the ester group of the compound 3 is subjected to alkaline hydrolysis and acidification to obtain a carboxylic acid group.
When hydrazine hydrate is used as a reactant, the method further comprises the step of carrying out methylation reaction on a cyclization reaction product before the alkaline hydrolysis, and specifically, the synthesis route of the pyrazole herbicide intermediate shown in the formula (ii) is as follows:
the specific synthesis process is as follows: the aldehyde group and carbonyl group are relatively active, and are easy to perform condensation reaction with hydrazine or amine compounds, water is removed and the ring is closed to obtain a compound 4, the compound 4 is methylated to obtain a compound 3, and the ester group of the compound 3 is subjected to alkaline hydrolysis and acidification to obtain a carboxylic acid group.
In some embodiments of the invention, the cyclization reactions in both synthetic routes described above are carried out in an organic solvent selected from at least one of toluene, chlorobenzene, cyclohexane, dichloroethane, methanol, isopropanol, ethanol, tetrahydrofuran, propylene oxide or 1, 2-butylene oxide, preferably at least one of toluene, cyclohexane, dichloroethane, methanol or isopropanol;
and/or the temperature of the cyclization reaction is-20 to 70 ℃, preferably-10 to 60 ℃; the time is 3 to 7 hours, preferably 4 to 7 hours.
In some embodiments of the present invention, the methylation reagent used in the methylation reaction is selected from at least one of dimethyl sulfate, dimethyl carbonate, methyl chloride, methyl p-toluenesulfonate or trimethyl phosphate, preferably dimethyl sulfate and/or dimethyl carbonate;
and/or, the temperature of the methylation reaction is 30-90 ℃; the time is 5-8 hours.
In some embodiments of the invention, the alkali used for the alkaline hydrolysis is selected from at least one of sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium carbonate or sodium carbonate, preferably sodium hydroxide and/or potassium hydroxide;
and/or the reaction temperature of the alkaline hydrolysis is 30-110 ℃, preferably 40-100 ℃; the time is 3 to 8 hours, preferably 4 to 7 hours.
In some embodiments of the invention, the acid used for the acidification is hydrochloric acid or sulfuric acid.
The beneficial effects of the invention are as follows:
1) The method uses the ethyl formate which is low in price, weak in corrosiveness and easy to recycle as the reactant, has the advantages of environment friendliness, safety and low cost, and is suitable for industrial production. Meanwhile, the invention can obtain the compound shown in the formula (i) with higher purity and yield, and the reaction product can be directly used for preparing the compound shown in the formula (ii) without purification treatment.
2) The method can obtain the compound shown in the formula (ii) with higher purity and yield, and in alkaline hydrolysis, the compound 3 is not required to be separated and purified, and the alkali is directly added into the previous reaction system, so that the reaction operation is simplified, the reaction efficiency is improved, the production cost is reduced, and the method is suitable for industrial production.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present invention more apparent, the technical solutions in the present invention will be clearly and completely described in the following, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
26g (0.2 mol) of ethyl acetoacetate, 50g of methanol and 14.96g (0.22 mol) of sodium ethoxide are added into a 250ml four-port bottle with a mechanical stirrer, a thermometer and a condenser tube, stirring and heating are carried out, 15.54g (0.21 mol) of ethyl formate is dropwise added when the temperature is raised to 50 ℃, after the dropwise addition is completed in 2 hours, the temperature is kept at 60 ℃, the reaction is carried out for 3 hours, hydrochloric acid is dropwise added to adjust the pH value to 4-5 to obtain a compound (with the reduced purity of 98 percent and the ethyl acetoacetate accounting for 98.5%) shown in the formula (i), the temperature is reduced to 0 ℃, 21.9g (0.2 mol) of 42 percent methyl hydrazine solution is dropwise added when the temperature is raised to 70 ℃ for 4 hours, 30.4g (0.3 mol) of 36 percent hydrochloric acid solution is dropwise added from a solvent, solid is separated, the solid is filtered and the reaction is dried to obtain 27.25g of the compound (with the purity of 96.8 percent) shown in the formula (ii), and the total yield is 94.2 percent.
Example 2
26g (0.2 mol) of ethyl acetoacetate, 50g of ethanol and 22.22g (0.22 mol) of triethylamine are added into a 250ml four-port bottle with a mechanical stirring thermometer and a condenser tube, stirring and heating are carried out, 15.54g (0.21 mol) of ethyl formate is dropwise added when the temperature is raised to 40 ℃, after the dropwise addition is completed within 2 hours, 50 ℃ is kept for reaction, 3 hours of hydrochloric acid is dropwise added for regulating the pH value to be 4-5 to obtain a compound (with the reduced purity of 98.2 percent and the ethyl acetoacetate accounting for 98.3 percent) shown in the formula (i), the temperature is reduced to 0 ℃ and 21.9g (0.2 mol) of 42% methyl hydrazine solution is dropwise added, 53.3g (0.4 mol) of 30.4g (0.3 mol) of 36% hydrochloric acid solution is dropwise added for reaction at 70 ℃ for 4 hours, the solid is separated, the compound (with the purity of 97.3 percent shown in the formula (ii) is obtained after filtration and drying, and the total yield of 93.8 percent of ethyl acetoacetate is obtained after the reaction.
Example 3
26g (0.2 mol) of ethyl acetoacetate, 50g of methanol and 11.88g (0.22 mol) of sodium methoxide are added into a 250ml four-port bottle with a mechanical stirring thermometer and a condenser tube, the temperature is raised by stirring, 15.54g (0.21 mol) of ethyl formate is added dropwise after 2 hours, the temperature is kept at 60 ℃ for reaction, 3 hours of hydrochloric acid is added dropwise to adjust the pH value to 4-5 to obtain a compound (with the reduced purity of 98.1 percent and the ethyl acetoacetate accounting for 98.5 percent) shown in the formula (i), the temperature is lowered to 0 ℃, 12.5g (0.2 mol) of 80 percent hydrazine hydrate solution is added, the temperature is kept for 3 hours, 15.9g (0.15 mol) of sodium carbonate is added, the temperature is raised by dropwise adding 27.72g (0.22 mol) of dimethyl sulfate at 70 ℃, the temperature is raised by dropwise adding 53.3g (0.4 mol) of 30 percent sodium hydroxide solution, the temperature is raised to 70 ℃ for reaction for 5 hours, 40.6g (0.4 mol) of 36 percent hydrochloric acid solution is dropwise separated, solid is separated by filtering, and the ethyl acetoacetate is dried to obtain a compound (with the purity of 93 percent shown in the formula (ii) shown in the formula (13 percent) accounting for the total purity of 93 percent) shown in the formula (ii) in the formula (i) in the four-port bottle, and the four-port bottle is filled with mechanical stirring, and is filled with 250ml four-port bottle
Comparative example 1
The compound of formula (ii) is prepared according to the existing method and its synthetic route is as follows:
the method specifically comprises the following steps:
in a 500ml four-mouth bottle with mechanical stirring, a thermometer and a condenser, 0.2mol of acetoacetate compound, 0.6mol of acetic anhydride and 0.48mol of triethyl orthoformate are added, the temperature is raised to 125 ℃ for reflux reaction for 2 hours, the later reflux temperature is reduced to 104 ℃, and the acetoacetate is controlled to be less than 1% in gas chromatography. The acetic acid mixture is distilled off under reduced pressure to 110 ℃, and 240g of absolute methanol is added at 10 ℃ in a cooling way. Stirring and controlling the reaction temperature to be 10-15 ℃, dropwise adding 0.33mol of methyl hydrazine, reacting for 4 hours at 20-30 ℃ after the addition is completed, decompressing and removing methanol, adding 0.4mol of 30% sodium hydroxide solution, heating to 70 ℃ for reacting for 4 hours, removing solvent, dropwise adding hydrochloric acid, adjusting pH to be 2-3, precipitating solid, filtering and drying, and detecting and calculating to obtain the compound shown in the formula (ii) with the purity of 82% and the yield of 53%.
And, from the course of this process, it can be seen that: a large amount of isomer 1, 2-dimethylpyrazole-3-carboxylic acid is generated, the yield is affected, acetic anhydride is used in the process, a large amount of acetic acid by-product is generated, and the acetic acid by-product is difficult to treat, so that the process is not easy for environmental protection production.
Comparative example 2
The compound of formula (ii) is prepared according to the existing method and its synthetic route is as follows:
in a 500ml four-port flask equipped with a mechanical stirrer, a thermometer and a condenser tube, 65.7g (0.3 mol) of 3-bromopyrazole-4-ethyl formate, 200g of DMF, 46.8g (0.33 mol) of methyl boric acid and 20g (0.33 mol) of 80 ℃ were added dropwise, the mixture was kept at 80 ℃ for 2 hours after the dropwise addition, 20.7g (0.15 mol) of potassium carbonate was added, the mixture was kept at 80 ℃ for 3 hours, the mixture was desolventized under reduced pressure, 53.3g (30% 0.4 mol) of sodium hydroxide was added, the mixture was heated to 70 ℃ and reacted for 5 hours, 30.4g (36% 0.3 mol) of hydrochloric acid was added dropwise to precipitate a solid, and the solid was filtered and dried, and the purity of the compound represented by the formula (ii) was 70% by detection and calculation, and the yield was 42%.
Comparative example 3
26g (0.2 mol) of ethyl acetoacetate, 50g of ethanol and 22.22g (0.22 mol) of triethylamine are added into a 250ml four-port bottle with a mechanical stirring device, a thermometer and a condenser tube, 15.54g (0.21 mol) of ethyl formate is added dropwise at the temperature of 20 ℃ after 2 hours, the reaction is carried out at the temperature of 30 ℃ for 5 hours, hydrochloric acid is added dropwise to adjust the pH value to 4-5 to obtain a compound (with the reduced purity of 89.6 percent and the ethyl acetoacetate accounting for 87.1 percent) shown in the formula (i), the temperature is reduced to 0 ℃ and 42% of methyl hydrazine solution (0.2 mol), 53.3g (0.4 mol) of 30% of sodium hydroxide solution is added to react for 4 hours, the reaction is carried out at the temperature of 70 ℃ for 5 hours, 30.4g (0.3 mol) of 36% of hydrochloric acid solution is added dropwise from a solvent to precipitate solid, the solid is filtered and the compound (with the purity of 93.4 percent) shown in the formula (ii) is obtained after drying, and the total yield of 51 percent is calculated by ethyl acetoacetate.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (8)
1. A preparation method of a pyrazole herbicide intermediate shown in a formula (ii) is characterized in that ethyl acetoacetate and ethyl formate are subjected to addition reaction under the action of alkali to obtain a compound shown in the formula (i); then carrying out cyclization reaction with methyl hydrazine/hydrazine hydrate, and finally carrying out alkaline hydrolysis and acidification to obtain a compound shown in a formula (ii); wherein the structure of the compound shown in the formula (i) and the formula (ii) is as follows:
；
formula (i) formula (ii);
the base is selected from any one of sodium methoxide, sodium ethoxide and triethylamine;
the addition reaction is carried out in the presence of an organic solvent selected from at least one of toluene, cyclohexane, dichloroethane, methanol and isopropanol;
the cyclization reaction is carried out in an organic solvent, wherein the organic solvent is at least one selected from toluene, cyclohexane, dichloroethane, methanol and isopropanol;
the temperature of the cyclization reaction is-10-60 ℃; the time is 4-7 hours.
2. The process for producing a pyrazole herbicide intermediate of the formula (ii) according to claim 1, wherein the molar ratio of the acetoacetic acid ethyl ester to the formic acid ethyl ester to the base is 1 (1.05-1.5): 1.1-2.0.
3. The method for producing a pyrazole herbicide intermediate of formula (ii) according to claim 1 or 2, wherein the temperature of the addition reaction is 40 to 70 ℃; the time is 3-5 hours.
4. The method for producing a pyrazole herbicide intermediate of formula (ii) according to claim 1, wherein when hydrazine hydrate is used as a reactant, the method further comprises a methylation reaction of a product of the cyclization reaction, wherein a methylation reagent used in the methylation reaction is at least one selected from dimethyl sulfate, dimethyl carbonate, methyl chloride, methyl p-toluenesulfonate and trimethyl phosphate;
and/or, the temperature of the methylation reaction is 30-90 ℃; the time is 5-8 hours.
5. The method for producing a pyrazole herbicide intermediate of formula (ii) according to claim 4, wherein the methylation reagent used in the methylation reaction is selected from dimethyl sulfate and/or dimethyl carbonate.
6. The method for producing a pyrazole herbicide intermediate of formula (ii) according to claim 1, wherein the alkali used for the alkaline hydrolysis is at least one selected from sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium carbonate and sodium carbonate;
and/or, the alkaline hydrolysis temperature is 40-100 ℃; the time is 4-7 hours.
7. The process for producing a pyrazole herbicide intermediate of the formula (ii) according to claim 6, wherein the base used for the alkaline hydrolysis is selected from sodium hydroxide and/or potassium hydroxide.
8. The process for producing a pyrazole herbicide intermediate of the formula (ii) according to claim 1, wherein the acid used for the acidification is hydrochloric acid or sulfuric acid.
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