CN114989142A - Preparation method of pyrazole compound - Google Patents

Preparation method of pyrazole compound Download PDF

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CN114989142A
CN114989142A CN202210497718.0A CN202210497718A CN114989142A CN 114989142 A CN114989142 A CN 114989142A CN 202210497718 A CN202210497718 A CN 202210497718A CN 114989142 A CN114989142 A CN 114989142A
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bromo
chloro
hexenyl
group
pentenyl
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邹亚波
张峰博
沈盛丰
郭少康
耿昆明
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Shenyang Wanling Biotechnology Co ltd
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Shenyang Wanling Biotechnology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Abstract

The invention discloses a preparation method of a pyrazole compound (I), which comprises the following steps:
Figure DDA0003633460570000011
dissolving the compound shown in the general formula (II) and the compound shown in the general formula (III) in a proper solvent in the presence of an alkaline substance and a catalyst, heating, reacting with CO under pressure and acidifying to obtain the compound shown in the general formula (II); in the general formulae (I), (II) and (III): r 1 、R 4 、R 5 Each independently selected from hydrogen, nitro, halogen, cyano, formyl, thiocyanato and (C) 1 ‑C 6 ) -an alkyl group; r is 2 、R 3 Each independently selected from hydrogen, cyano, formyl, thiocyanato, (C) 1 ‑C 6 ) A straight or branched alkyl or haloalkyl group of (a), a phenyl group substituted with 1 to 5 halogens, an aryl group substituted with 1 to 5 alkyl or haloalkyl groups, and a N-containing heterocyclic aromatic group; r 6 Is selected from the group consisting ofAlkyl, ethyl, isopropyl; r 7 Is selected from (C) 1 ‑C 6 ) Alkyl, (C) 3 ‑C 6 ) -a cycloalkyl group; r 8 Selected from chlorine, bromine or iodine; n is selected from 0-2.

Description

Preparation method of pyrazole compound
Technical Field
The invention belongs to the technical field of pesticide preparation, and particularly relates to a method for preparing HPPD herbicide pyrazole compounds.
Background
The p-hydroxyphenyl pyruvate dioxygenase (4-HPPD) is confirmed as a herbicide action target in the last 90 s, and the compounds have the characteristics of high efficiency, low toxicity, environmental friendliness, various structures and the like, and are used as herbicides in the most main application field. There are currently few reports of resistant weeds worldwide for such herbicides.
Most of pyrazole herbicides which are commercialized by pyrazole compounds are p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors, and the pyrazole herbicides are popular due to the characteristics of systemic property, extremely low toxicity to mammals and the like.
According to the research on a 4-HPPD herbicide system, CN110357859A designs and synthesizes a novel pyrazole 4-HPPD compound containing a quinazolinedione structure, and particularly discloses a compound shown in formula (I) obtained by carrying out cyanation, hydrolysis, acyl chlorination, esterification and rearrangement on the pyrazole compound for 5 steps
Figure BDA0003633460560000011
However, the compounds of the structure of formula (I) in this prior art process are expensive to purchase; the self-synthesis has the defects of complex process route, low yield, long period, high energy consumption, large amount of three wastes and the like.
Therefore, a preparation method of pyrazole compounds with simple and direct reaction route, high yield, high purity and environmental friendliness is urgently needed.
Disclosure of Invention
The invention aims to provide a preparation method of a pyrazole compound, which has the advantages of simple reaction route, high yield, high purity and environmental friendliness.
In order to achieve the above object, according to one aspect of the present invention, there is provided a process for producing a pyrazole compound represented by the formula (I):
Figure BDA0003633460560000021
dissolving a compound shown in a formula (II) and a compound shown in a formula (III) in a solvent in the presence of an alkaline substance and a catalyst, heating, reacting with CO at a reaction pressure of not less than 2Mpa and a reaction temperature of not less than 90 ℃, and acidifying after the reaction to obtain a pyrazole compound shown in a general formula (I);
wherein, in the general formulae (I), (II) and (III):
R 1 、R 4 、R 5 each independently selected from hydrogen, nitro, halogen, cyano, formyl, thiocyanato, (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Straight or branched haloalkyl of (A), (B), and (C) 2 -C 6 ) -alkenyl, (C) 2 -C 6 ) -haloalkenyl, (C) 2 -C 6 ) -alkynyl, (C) 2 -C 6 ) -haloalkynyl, (C) 3 -C 6 ) -cycloalkyl, (C) 3 -C 6 ) -halocycloalkyl, (C) 3 -C 6 ) -cycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 3 -C 6 ) -halocycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) alkyl-S (O) n (C 0 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -haloalkyl-S (O) n ；
R 2 、R 3 Each independently selected from hydrogen, cyano, formyl, thiocyanato, (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Linear or branched haloalkyl of (C) 2 -C 6 ) -alkenyl, (C) 2 -C 6 ) -haloalkenyl, (C) 2 -C 6 ) -alkynyl, (C) 2 -C 6 ) -haloalkynyl, (C) 3 -C 6 ) -cycloalkyl, (C) 3 -C 6 ) -halocycloalkyl, (C) 3 -C 6 ) -cycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 3 -C 6 ) -halocycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -alkoxy- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) alkyl-S (O) n (C 0 -C 6 ) Alkyl, (C) 1 -C 6 ) -haloalkyl-S (O) n Aryl, arylsulfonyl, phenyl substituted with 1-5 halogens, aryl substituted with 1-5 alkyl or haloalkyl groups, and N-containing heterocyclic aromatic groups;
R 6 selected from hydrogen or (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Linear or branched haloalkyl of (C) 3 -C 6 ) -a cycloalkyl group; such as methyl, ethyl, isopropyl;
R 7 selected from hydrogen, (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Linear or branched haloalkyl of (C) 3 -C 6 ) -a cycloalkyl group;
R 8 selected from chlorine, bromine or iodine;
n is selected from 0-2.
Preferably, R 1 、R 4 、R 5 Each independently selected from methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, chloro, bromo, iodo.
R 1 、R 4 、R 5 Further independently selected from the group consisting of chloroethyl, chloro-1-propenyl, chloro-2-propenyl, chloro-1-butenyl, chloro-2-butenyl, chloro-3-butenyl, chloro-1-pentenyl, chloro-2-pentenyl, chloro-3-pentenyl, chloro-4-pentenyl, chloro-1-hexenyl, chloro-2-hexenyl, chloro-3-hexenyl, chloro-4-hexenyl, chloro-5-hexenyl, bromo-vinyl, bromo-1-propenyl, bromo-2-propenyl, bromo-1-butenyl, bromo-2-butenyl, bromo-3-butenyl, bromo-1-pentenyl, bromo-2-pentenyl, bromo-3-pentenyl, bromo-4-pentenyl, bromo-1-hexenyl, bromo-2-hexenyl, bromo-3-hexenyl, bromo-hexenyl, and the like, Bromo-2-hexenyl, bromo-3-hexenyl, bromo-4-hexylAlkenyl, bromo 5-hexenyl.
R 2 、R 3 Each independently selected from methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, chloro, bromo, iodo.
R 2 、R 3 Further independently selected from the group consisting of chloroethyl, chloro-1-propenyl, chloro-2-propenyl, chloro-1-butenyl, chloro-2-butenyl, chloro-3-butenyl, chloro-1-pentenyl, chloro-2-pentenyl, chloro-3-pentenyl, chloro-4-pentenyl, chloro-1-hexenyl, chloro-2-hexenyl, chloro-3-hexenyl, chloro-4-hexenyl, chloro-5-hexenyl, bromo-vinyl, bromo-1-propenyl, bromo-2-propenyl, bromo-1-butenyl, bromo-2-butenyl, bromo-3-butenyl, bromo-1-pentenyl, bromo-2-pentenyl, bromo-3-pentenyl, bromo-4-pentenyl, bromo-1-hexenyl, bromo-2-hexenyl, bromo-3-hexenyl, bromo-hexenyl, and the like, Bromo-2-hexenyl, bromo-3-hexenyl, bromo-4-hexenyl, bromo-5-hexenyl.
Preferably, R 2 、R 3 Each independently selected from imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyridazinyl, triazinyl, 3-chlorophenyl, 2, 4-dichlorophenyl, 4-chloro-2-pyridyl, 4-methylphenyl, 2, 6-dimethylphenyl, 4-methyl-2-pyridyl.
Preferably, the molar ratio of the compound represented by the general formula (II) to the compound represented by the general formula (III) is 1 (1-1.1), and more preferably 1 (1-1.05).
According to the invention, the catalyst contains a component A and a component B, and the molar ratio of the component A calculated by palladium element to the component B is 1 (1-2). Preferably, the component a is selected from palladium chloride, palladium acetate or tetrakis (triphenylphosphine) palladium; the component B is selected from ligands of 2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl, 2-dicyclohexylphosphine-2', 6 '-dimethoxy-1, 1' -biphenyl, 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, bis (2-diphenylphosphinophenyl) ether and/or 4, 5-bis-diphenylphosphino-9, 9-dimethylxanthene.
According to the invention, the molar ratio of the compound of the general formula (II) to the amount of component A in the catalyst is 1 (0.001-0.5); the preferred molar ratio is 1 (0.001-0.01).
According to the invention, the alkaline substance is one or more of sodium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, DBU, DIPEA, triethylamine and pyridine.
Preferably, the basic substance is one or more of sodium hydroxide, potassium carbonate, sodium bicarbonate, cesium carbonate, DBU and triethylamine.
Preferably, the molar ratio of the compound represented by the formula (II) to the basic substance is 1 (1-3), and preferably 1 (1-2).
According to the invention, the acidification is carried out by at least one of hydrochloric acid, sulfuric acid and acetic acid; preferably, hydrochloric acid or sulfuric acid is used for acidification. Preferably, the acidification step is to adjust the pH to 2-3 with an acid.
According to the invention, the solvent is selected from one or more of dichloroethane, acetonitrile, diethyl ether, toluene, chlorobenzene, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, NMP, DMF and DMSO.
Preferably, the solvent is selected from one or more of acetonitrile, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, toluene and DMF.
According to the invention, the reaction conditions for preparing the pyrazole compound shown in the formula (I) are as follows:
the reaction pressure is as follows: 2 to 10MPa, preferably 3 to 8MPa, preferably 5 to 8MPa, more preferably 4 to 6 MPa;
the reaction temperature is as follows: 90-180 ℃, for example, 100 ℃ to 160 ℃, 120 ℃ to 150 ℃.
The reaction time is as follows: from 0.2 to 48 hours, for example from 0.5 to 40 hours; 1-36 hours, 2-30 hours, 3-24 hours, 4-20 hours, 5-12 hours and the like.
Specifically, dissolving the compound shown in the formula (II) and the compound shown in the formula (III) in acetonitrile solvent, introducing nitric oxide gas into a reaction kettle for replacing for 3 times, then introducing the carbon monoxide gas for replacing for 2 times, then increasing the pressure of the reaction kettle to 5.0Mpa, starting stirring, raising the temperature to 150 ℃, and carrying out heat preservation reaction for 20 hours.
According to another aspect of the invention, a preparation method of the pyrazole compound shown in the formula (1), the formula (5) and the formula (7) is also provided, and the reaction is sequentially as follows:
Figure BDA0003633460560000051
compared with the prior art, the invention has the following characteristics:
the invention adopts the carbon monoxide carbonyl insertion method to synthesize the pyrazole compound shown in the general formula (I) in one step, directly obtains a target object, avoids introducing cyanide ions by cyanation and using a large amount of sulfuric acid for hydrolysis, overcomes the defects that a virulent catalyst acetone cyanohydrin is needed in a rearrangement method after carboxyl acyl chloride is converted into ester, reduces reaction steps, shortens reaction time, simplifies operation process, reduces energy consumption, reduces three wastes, achieves the effects of high yield and high purity, is environment-friendly, and is suitable for large-scale industrial production.
Detailed Description
The present invention will be described in further detail with reference to examples. These examples should not be construed as limiting the scope of the invention. All the technologies realized based on the above-mentioned contents of the present invention are covered in the protection scope of the present invention.
Definition of terms
(C 3 -C 6 ) Cycloalkyl includes cyclic chain forms including cyclopropyl, methylcyclopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
(C 3 -C 6 ) Halocycloalkyl includes cyclic chain forms including halocyclopropyl, halomethylcyclopropyl, halocyclopropyl, halocyclobutyl, halocyclopentyl, halocyclohexyl. Preferably chlorocyclopropyl, chloromethylcyclopropyl, chlorocyclopropylcyclopropyl, chlorocyclobutyl, chlorocyclopentyl, chlorocyclohexyl, bromocyclopropyl, bromomethylcyclopropyl, bromocyclopropylcyclopropyl, bromocyclopropylButyl, bromocyclopentyl, bromocyclohexyl.
(C 2 -C 6 ) Alkenyl is a straight-chain or branched alkenyl, for example selected from vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl.
(C 2 -C 6 ) Haloalkenyl is a straight-chain or branched haloalkenyl, such as haloethenyl, halo-1-propenyl, halo-2-propenyl, halobutenyl, halopentynyl or halohexenyl.
(C 2 -C 6 ) Alkynyl is straight-chain or branched alkynyl, for example selected from ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl.
(C 2 -C 6 ) -haloalkynyl is a linear or branched haloalkynyl, for example selected from the group consisting of haloalkynyl, 1-propynyl, 2-propynyl, butynyl, pentynyl and hexynyl; further independently selected from the group consisting of ethynylchloride, 1-propynyl chloride, 2-propynyl chloride, 1-butynyl chloride, 2-butynyl chloride, 3-butynyl chloride, 1-pentynyl chloride, 2-pentynyl chloride, 3-pentynyl chloride, 4-pentynyl chloride, 1-hexynyl chloride, 2-hexynyl chloride, 3-hexynyl chloride, 4-hexynyl chloride, 5-hexynyl chloride, ethynylbromide, 1-propynyl bromide, 2-propynyl bromide, 1-butynyl bromide, 2-butynyl bromide, 3-butynyl bromide, 1-pentynyl bromide, 2-pentynyl bromide, 3-pentynyl bromide, 4-pentynyl bromide, 1-hexynyl bromide, etc, Bromo-2-hexynyl, bromo-3-hexynyl, bromo-4-hexynyl, bromo-5-hexynyl.
(C 3 -C 6 ) -cycloalkyl- (C) 1 -C 6 ) The alkyl group may be, for example, cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl, cyclopropylpentyl, cyclopropylhexyl, cyclobutylmethyl, cyclobutylethylButylpropyl, cyclobutylbutyl, cyclobutylpentyl, cyclobutylhexyl, cyclopentylmethyl, cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl, cyclopentylpentyl, cyclopentylhexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl, cyclohexylbutyl, cyclohexylpentyl or cyclohexylhexyl.
(C 3 -C 6 ) -halocycloalkyl- (C) 1 -C 6 ) The alkyl group may be, for example, a halogenated cyclopropylmethyl group, a halogenated cyclopropylethyl group, a halogenated cyclopropylpropyl group, a halogenated cyclopropylbutyl group, a halogenated cyclopropylpentyl group, a halogenated cyclopropylhexyl group, a halogenated cyclobutylmethyl group, a halogenated cyclobutylethyl group, a halogenated cyclobutylpropyl group, a halogenated cyclobutylbutyl group, a halogenated cyclobutylpentyl group, a halogenated cyclobutylhexyl group, a halogenated cyclopentylmethyl group, a halogenated cyclopentylethyl group, a halogenated cyclopentylbutyl group, a halogenated cyclopentylpentyl group, a halogenated cyclopentylhexyl group, a halogenated cyclohexylmethyl group, a halogenated cyclohexylethyl group, a halogenated cyclohexylpropyl group, a halogenated cyclohexylbutyl group, a halogenated cyclohexylpentyl group, a halogenated cyclohexylhexyl group;
further independently selected from the group consisting of chlorocyclopropylmethyl, chlorocyclopropylethyl, chlorocyclopropylpropyl, chlorocyclopropylbutyl, chlorocyclopropylpentyl, chlorocyclopropylhexyl, chlorocyclobutylmethyl, chlorocyclobutylethyl, chlorocyclobutylpropyl, chlorocyclobutylbutyl, chlorocyclobutylpentyl, chlorocyclobutylhexyl, chlorocyclopentylmethyl, chlorocyclopentylethyl, chlorocyclopentylpropyl, chlorocyclopentylbutyl, chlorocyclopentylpentyl, chlorocyclopentylhexyl, chlorocyclohexylmethyl, chlorocyclohexylethyl, chlorocyclohexylpropyl, chlorocyclohexylbutyl, chlorocyclohexylpentyl, chlorocyclohexylhexyl, bromocyclopropylmethyl, bromocyclopropylethyl, bromocyclopropylpropyl, bromocyclopropylbutyl, bromocyclopropylpentyl, bromocyclopropylhexyl, bromocyclobutylmethyl, bromocyclobutylethylpropyl, bromocyclobutylbutyl, chlorocyclopropylbutyl, chlorocyclohexylbutyl, chlorocyclohexylhexyl, chlorocyclohexylmethyl, bromocyclopropylmethyl, bromocyclopropylethyl, bromocyclopropylbutyl, bromocyclopropylpentyl, bromocyclopropylhexyl, bromocyclobutylmethyl, bromocyclobutylethylpropyl, chlorocyclobutylbutyl, chlorocyclopentylpropyl, chlorobutylbutyl, chlorocyclopentylpropyl, chlorobutylpentyl, chlorobutylhexyl, Bromo-cyclobutyl-propyl, bromo-cyclobutyl-butyl, bromo-cyclobutyl-pentyl, bromo-cyclobutyl-hexyl, bromo-cyclopentyl-methyl, bromo-cyclopentyl-ethyl, bromo-cyclopentyl-propyl, bromo-cyclopentyl-butyl, bromo-cyclopentyl-pentyl, bromo-cyclopentyl-hexyl, bromo-cyclohexyl-methyl, bromo-cyclohexyl-ethyl, bromo-cyclohexyl-propyl, bromo-cyclohexyl-butyl, bromo-cyclohexyl-pentyl, bromo-cyclohexyl-hexyl.
(C 1 -C 6 ) -alkoxy- (C) 1 -C 6 ) The alkoxy group in the alkyl group is a group having an oxygen atom at the terminal of the alkyl group, and may be, for example, a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group, a sec-butoxy group, or a tert-butoxy group.
(C 1 -C 6 ) alkyl-S (O) n (C 0 -C 6 ) Alkyl can be, for example, methylthio, ethylthio, methylthiomethyl, ethylthiomethyl, methylsulfinyl, ethylsulfinyl, methylsulfinylmethyl, ethylsulfinylmethyl, methylsulfonyl, ethylsulfonyl, methylsulfonylmethyl, ethylsulfonylmethyl;
(C 1 -C 6 ) haloalkyl-S (O) n For example, difluoromethanesulfonyl, trifluoromethanesulfonyl;
said aryl group is C 6-20 Monocyclic or fused rings of (a), such as phenyl, naphthyl, anthracenyl and the like;
the nitrogen-containing heteroaryl group is a 5-to 20-membered monocyclic or fused ring containing at least one nitrogen atom, such as pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl and the like.
Preferably, the molar ratio of the compound shown in the general formula (II) to the compound shown in the general formula (III) is 1 (1-1.1), and the preferred molar ratio is 1 (1-1.05). Controlling the molar ratio of the two compounds within the above range allows more thorough reaction of the raw materials, higher yield, and simplified post-treatment operation, otherwise the raw materials remain, resulting in waste and complicated post-treatment.
According to the invention, the catalyst contains a component A and a component B, wherein the molar ratio of the amount of the component A calculated by palladium element to the content of the component B is 1 (1-2). By controlling the molar ratio of the consumption of the palladium element in the component A to the content of the component B, the palladium element and the ligand can be completely complexed, the catalytic efficiency can be better improved, otherwise, the catalyst is easy to waste, the reaction efficiency is reduced, and even the reaction is incomplete.
Preferably, the component a is selected from palladium chloride, palladium acetate or tetrakis (triphenylphosphine) palladium; the component B is selected from ligands of 2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl, 2-dicyclohexylphosphine-2', 6 '-dimethoxy-1, 1' -biphenyl, 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, bis (2-diphenylphosphinophenyl) ether and/or 4, 5-bis-diphenylphosphino-9, 9-dimethylxanthene. The catalyst can be used for more thoroughly carrying out the reaction and reducing the occurrence of side reactions, and is low in price and suitable for industrial production.
Preferably, the molar ratio of the compound shown in the formula (II) to the amount of the component A in the catalyst is 1 (0.001-0.5); the preferred molar ratio is 1 (0.001-0.01). The invention controls the molar ratio of the two in the range, has higher yield and purity, saves cost, is suitable for industrial production, otherwise, the yield is easily reduced, impurities are generated, and the waste of raw materials or the cost is increased.
The alkaline substance adopted by the invention can be one or more of sodium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, DBU, DIPEA, triethylamine and pyridine. Further preferred is one or more of sodium hydroxide, potassium carbonate, sodium hydrogencarbonate, cesium carbonate, DBU and triethylamine. The above basic substances are preferred in the present invention but are not limited thereto.
Preferably, the molar ratio of the compound represented by the general formula (II) to the basic substance is 1 (1-3), and preferably 1 (1-2). By controlling the molar ratio of the compound represented by the general formula (II) to the basic substance within the above range, the post-treatment operation can be simplified, otherwise, too little reaction is incomplete, too much post-treatment difficulty is increased, and raw materials are wasted.
According to the invention, the acidification is carried out by at least one of hydrochloric acid, sulfuric acid and acetic acid; preferably, hydrochloric acid or sulfuric acid is used for acidification. Preferably, the acidification step is to adjust the pH to 2-3 with an acid. The final product can be obtained by adopting acidification reaction treatment to enable the product to exist in the solvent in the form of inorganic salt or organic salt.
Preferably, the solvent is selected from one or more of dichloroethane, acetonitrile, diethyl ether, toluene, chlorobenzene, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, NMP, DMF and DMSO. Further preferably, the solvent is selected from one or more of acetonitrile, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, toluene and DMF. The solvent is preferably used in the present invention, but not limited thereto, as long as it can dissolve the reactants and the products to promote the reaction to proceed thoroughly.
According to the invention, the reaction conditions for preparing the pyrazole compound shown in the formula (I) are as follows:
the reaction pressure is as follows: 2 to 10MPa, preferably 3 to 8MPa, preferably 5 to 8MPa, more preferably 4 to 6 MPa;
the reaction temperature is as follows: 90-180 ℃, such as 100 ℃ and 160 ℃, and 120 ℃ and 150 ℃.
The reaction time is as follows: from 0.2 to 48 hours, for example from 0.5 to 40 hours; 1-36 hours, 2-30 hours, 3-24 hours, 4-20 hours, 5-12 hours and the like.
For example, the compound represented by the formula (II) and the compound represented by the formula (III) are dissolved in acetonitrile solvent, nitrogen monoxide gas is introduced into a reaction kettle for 3 times of replacement, carbon monoxide gas is introduced for 2 times of replacement, then the pressure of the reaction kettle is increased to 5.0Mpa, stirring is started, the temperature is increased to 150 ℃, and the reaction is carried out for 20 hours under the condition of heat preservation.
The technical scheme of the invention is further explained by combining specific examples.
Example 1
Figure BDA0003633460560000101
Adding 20mg of a compound shown in a formula 2 (10.00g, 26.34mmol), a compound shown in a formula 3 (2.95g, 26.34mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of palladium chloride of a component A to bis (2-diphenylphosphinophenyl) ether of a component B is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, heating to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the carbonyl insertion product, namely the compound of the formula 1, 10.21g of yellow solid, wherein the yield is 87.44%, and the purity is 99%.
Example 2
Adding 20mg of a compound (10.00g, 26.34mmol) of formula 2, a compound (2.95g, 26.34mmol) of formula 3, sodium carbonate (13.96g, 131.70mmol), triethylamine (13.33g, 131.70mmol), a catalyst (the molar ratio of palladium chloride of component A to bis (2-diphenylphosphinophenyl) ether of component B is 1:1.5), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, raising the pressure of the reaction kettle to 5.0MPa, starting stirring, raising the temperature to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 1, of the carbonyl insertion product, wherein 10.32g of white solid is obtained, the purity is 99%, and the yield is 88.38%.
Example 3
Adding 20mg of a compound (10.00g, 26.34mmol) of formula 2, a compound (2.95g, 26.34mmol) of formula 3, sodium carbonate (9.77g, 92.19mmol), triethylamine (9.33g, 92.19mmol), a catalyst (the molar ratio of palladium chloride of the component A to the component B4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, raising the pressure of the reaction kettle to 5.0MPa, starting stirring, raising the temperature to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 1, of the carbonyl insertion product, wherein 10.38g of white solid is obtained, the purity is 99%, and the yield is 88.89%.
Example 4
Adding 20mg of a compound shown in formula 2 (10.00g, 26.34mmol), a compound shown in formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the palladium chloride of the component A to the bis (2-diphenylphosphinophenyl) ether of the component B is 1:2), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, heating to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases for two times, and then desolventizing to obtain the product of the carbonyl insertion product, namely the compound of formula 1, 10.56g of white solid, the purity of 99 percent and the yield of 90.43 percent.
Example 5
Adding 20mg of a compound (10.00g, 26.34mmol) of formula 2, a compound (3.25g, 28.97mmol) of formula 3, sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of palladium chloride of component A to bis (2-diphenylphosphinophenyl) ether of component B is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 7.0MPa, starting stirring, heating to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 1, of the carbonyl insertion product, wherein 10.48g of white solid is obtained, the purity is 99%, and the yield is 89.75%.
Example 6
Adding 20mg of a compound shown in formula 2 (10.00g, 26.34mmol), a compound shown in formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the palladium chloride of the component A to the bis (2-diphenylphosphinophenyl) ether of the component B is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, heating to 120 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 1, of the carbonyl insertion product, wherein 10.21g of white solid is obtained, the purity is 99%, and the yield is 87.44%.
Example 7
Adding 20mg of a compound of formula 2 (10.00g, 26.34mmol), a compound of formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the palladium chloride as component A to the bis (2-diphenylphosphinophenyl) ether as component B is 1:1), adding 70mL of acetonitrile as a solvent, introducing nitric oxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, increasing the temperature to 180 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain 9.56g of a white solid of the compound of the formula 1 of the carbonyl insertion product, wherein the purity is 98.6%, and the yield is 81.85%.
Example 8
Adding 20mg of a compound shown in formula 2 (10.00g, 26.34mmol), a compound shown in formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the palladium chloride of the component A to the bis (2-diphenylphosphinophenyl) ether of the component B is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 8.0MPa, starting stirring, heating to 110 ℃, and preserving the temperature for reaction for 15 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain 9.42g of a white solid of the compound of the formula 1 of the carbonyl insertion product, wherein the purity is 98.4%, and the yield is 80.64%.
Example 9
Adding 20mg of a compound (10.00g, 26.34mmol) of formula 2, a compound (3.25g, 28.97mmol) of formula 3, sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of palladium chloride of component A to bis (2-diphenylphosphinophenyl) ether of component B is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, then increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, heating to 150 ℃, and preserving heat for 36 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 1, of the carbonyl insertion product, wherein 10.86g of white solid is obtained, the purity is 99%, and the yield is 93%.
Example 10
Adding 20mg of a compound (10.00g, 26.34mmol) of formula 2, a compound (3.25g, 28.97mmol) of formula 3, sodium carbonate (9.77g, 92.19mmol), triethylamine (9.33g, 92.19mmol), a catalyst (the molar ratio of the component A to the palladium chloride to the component B to the bis (2-diphenylphosphinophenyl) ether is 1:1), adding 70mL of dioxane serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, raising the pressure of the reaction kettle to 5.0MPa, starting stirring, raising the temperature to 180 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product of the intercalation product, namely the compound of formula 1, 10.74g of white solid, the purity of 99 percent and the yield of 91.98 percent.
Example 11
Figure BDA0003633460560000151
Adding 20mg of a compound of formula 4 (10.00g, 26.27mmol), a compound of formula 3 (2.95g, 26.27mmol), sodium carbonate (5.57g, 52.54mmol), triethylamine (5.31g, 52.54mmol), a catalyst (the molar ratio of the component A to the palladium chloride to the component B to the bis (2-diphenylphosphinophenyl) ether is 1:1), adding 70mL of dioxane serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, raising the pressure of the reaction kettle to 5.0MPa, starting stirring, raising the temperature to 120 ℃, and preserving the temperature for reaction for 36 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the carbonyl insertion product, namely the compound shown in the formula 5, which is 10.53g of light yellow solid, the purity of the compound is 99%, and the yield of the compound is 90.21%.
Example 12
Figure BDA0003633460560000152
Adding 20mg of a compound of formula 6 (10.00g, 24.59mmol), a compound of formula 3 (2.76g, 24.59mmol), sodium carbonate (5.21g, 49.18mmol), triethylamine (4.97g, 49.18mmol), a catalyst (the molar ratio of the component A to palladium chloride to the component B to bis (2-diphenylphosphinophenyl) ether is 1:1), adding 70mL of a dioxane solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, increasing the temperature to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 7, of the carbonyl insertion product, wherein the white solid is 10.36g, the purity is 99%, and the yield is 89.52%.
Example 13
Figure BDA0003633460560000161
Adding 20mg of a compound (10.00g, 24.59mmol) of formula 6, a compound (2.76g, 24.59mmol) of formula 3, sodium carbonate (5.21g, 49.18mmol), triethylamine (4.97g, 49.18mmol), a catalyst (the molar ratio of the component A to the palladium chloride to the component B to the bis (2-diphenylphosphinophenyl) ether is 1:4), adding 70mL of dioxane serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, raising the pressure of the reaction kettle to 5.0MPa, starting stirring, raising the temperature to 150 ℃, and preserving the temperature for reaction for 20 hours.
After the reaction is finished, cooling to room temperature, then decompressing the reaction kettle, filtering the reaction liquid, desolventizing the filtrate, adding 70mL of water to dissolve the filtrate and the filter cake, adjusting the pH value to 2-3 by using hydrochloric acid, adding 75mL of dichloromethane to extract for three times, layering, combining organic phases, washing the organic phases twice, and then desolventizing to obtain the product, namely the compound of the formula 7, of the carbonyl insertion product, wherein 10.36g of white solid is obtained, the purity is 94%, and the yield is 85.32%.
Comparative example 1
Adding 20mg of a compound shown in formula 2 (10.00g, 26.34mmol), a compound shown in formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the component A to the palladium chloride to the component B to the bis (2-diphenylphosphinophenyl) ether is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, increasing the pressure of the reaction kettle to 1.0Mpa, starting stirring, heating to 150 ℃, and preserving the temperature for reaction for 15 hours. By detection, no product formation is found. The pressure in the reaction kettle is increased to 5.0Mpa, the reaction is continued for 5 hours, and the product is generated after detection.
It can be seen that when the reaction kettle pressure is too low, the compound represented by formula 1 cannot be obtained.
Comparative example 2
Adding 20mg of a compound shown in formula 2 (10.00g, 26.34mmol), a compound shown in formula 3 (3.25g, 28.97mmol), sodium carbonate (5.58g, 52.68mmol), triethylamine (5.33g, 52.68mmol), a catalyst (the molar ratio of the component A to the palladium chloride to the component B to the bis (2-diphenylphosphinophenyl) ether is 1:1), adding 70mL of acetonitrile serving as a solvent, introducing nitrogen monoxide gas into the reaction kettle for replacement for 3 times, introducing carbon monoxide gas for replacement for 2 times, increasing the pressure of the reaction kettle to 5.0MPa, starting stirring, heating to 80 ℃, and carrying out heat preservation reaction for 15 hours. By detection, no product formation is found. And (4) heating the reaction kettle to 130 ℃, continuing to react for 5 hours, and detecting that a product is generated.
It can be seen that when the temperature of the reaction vessel is too low, the compound represented by formula 1 cannot be obtained.

Claims (10)

1. A preparation method of a pyrazole compound shown as a formula (I) is characterized by comprising the following steps:
Figure FDA0003633460550000011
dissolving a compound shown as a formula (II) and a compound shown as a formula (III) in a solvent under an alkaline condition and in the presence of a catalyst, heating, reacting with CO under the reaction pressure of not less than 2Mpa and the reaction temperature of not less than 90 ℃, and acidifying after the reaction to obtain a pyrazole compound shown as a general formula (I);
wherein, in the general formulae (I), (II) and (III):
R 1 、R 4 、R 5 each independently selected from hydrogen, nitro, halogen, cyano, formyl, thiocyanato, (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Linear or branched haloalkyl of (C) 2 -C 6 ) -alkenyl, (C) 2 -C 6 ) -haloalkenyl, (C) 2 -C 6 ) -alkynyl, (C) 2 -C 6 ) -haloalkynyl, (C) 3 -C 6 ) -cycloalkyl, (C) 3 -C 6 ) -halocycloalkyl, (C) 3 -C 6 ) -cycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 3 -C 6 ) -halocycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) alkyl-S (O) n (C 0 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -haloalkyl-S (O) n ；
R 2 、R 3 Each independently selected from hydrogen, cyano, formyl, thiocyanato, (C) 1 -C 6 ) Straight or branched alkyl of (2), C 1 -C 6 Linear or branched haloalkyl of (C) 2 -C 6 ) -alkenyl, (C) 2 -C 6 ) -haloalkenyl, (C) 2 -C 6 ) -alkynyl, (C) 2 -C 6 ) -haloalkynyl, (C) 3 -C 6 ) -cycloalkyl, (C) 3 -C 6 ) -halocycloalkyl, (C) 3 -C 6 ) -cycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 3 -C 6 ) -halocycloalkyl- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -alkoxy- (C) 1 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -alkyl-S (O) n (C 0 -C 6 ) Alkyl radicals, (C) 1 -C 6 ) -haloalkyl-S (O) n Aryl, arylsulfonyl, phenyl substituted with 1-5 halogens, aryl substituted with 1-5 alkyl or haloalkyl groups, and N-containing heterocyclic aromatic groups;
R 6 selected from hydrogen or (C) 1 -C 6 ) Straight or branched alkyl of、(C 1 -C 6 ) Linear or branched haloalkyl of (C) 3 -C 6 ) -a cycloalkyl group; such as methyl, ethyl, isopropyl;
R 7 selected from hydrogen, (C) 1 -C 6 ) Straight or branched alkyl of (C) 1 -C 6 ) Linear or branched haloalkyl of (C) 3 -C 6 ) -a cycloalkyl group;
R 8 selected from chlorine, bromine or iodine; n is selected from 0-2.
2. The method of claim 1, wherein R is 1 、R 4 、R 5 Each independently selected from methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, chloro, bromo, iodo;
R 1 、R 4 、R 5 further independently selected from the group consisting of chloroethyl, chloro-1-propenyl, chloro-2-propenyl, chloro-1-butenyl, chloro-2-butenyl, chloro-3-butenyl, chloro-1-pentenyl, chloro-2-pentenyl, chloro-3-pentenyl, chloro-4-pentenyl, chloro-1-hexenyl, chloro-2-hexenyl, chloro-3-hexenyl, chloro-4-hexenyl, chloro-5-hexenyl, bromo-vinyl, bromo-1-propenyl, bromo-2-propenyl, bromo-1-butenyl, bromo-2-butenyl, bromo-3-butenyl, bromo-1-pentenyl, bromo-2-pentenyl, bromo-3-pentenyl, bromo-4-pentenyl, bromo-1-hexenyl, bromo-2-hexenyl, bromo-3-hexenyl, bromo-hexenyl, and the like, Bromo-2-hexenyl, bromo-3-hexenyl, bromo-4-hexenyl, bromo-5-hexenyl.
Preferably, R 2 、R 3 Each independently selected from methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, chloro, bromo, iodo;
R 2 、R 3 further independently selected from the group consisting of a chloroethyl group, a chloro-1-propenyl group, a chloro-2-propenyl group, a chloro-1-butenyl group, a chloro-2-butenyl group, a chloro-3-butenyl group, a chloro-1-pentenyl group, a chloro-2-pentenyl group, a chloro-3-pentenyl group, a chloro-4-pentenyl group, a chloro-1-hexenyl group,Chloro 2-hexenyl, chloro 3-hexenyl, chloro 4-hexenyl, chloro 5-hexenyl, bromo vinyl, bromo 1-propenyl, bromo 2-propenyl, bromo 1-butenyl, bromo 2-butenyl, bromo 3-butenyl, bromo 1-pentenyl, bromo 2-pentenyl, bromo 3-pentenyl, bromo 4-pentenyl, bromo 1-hexenyl, bromo 2-hexenyl, bromo 3-hexenyl, bromo 4-hexenyl, bromo 5-hexenyl.
Preferably, R 2 、R 3 Each independently selected from imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyridazinyl, triazinyl, 3-chlorophenyl, 2, 4-dichlorophenyl, 4-chloro-2-pyridyl, 4-methylphenyl, 2, 6-dimethylphenyl, 4-methyl-2-pyridyl.
3. The process according to claim 1, wherein the molar ratio of the compound of formula (II) to the compound of formula (III) is 1 (1-1.1), preferably 1 (1-1.05).
4. The preparation method according to claim 1, wherein the catalyst comprises a component A and a component B, and the molar ratio of the component A calculated as palladium element to the component B is 1 (1-2).
Preferably, the component a is selected from palladium chloride, palladium acetate or tetrakis (triphenylphosphine) palladium; the component B is selected from ligands of 2-dicyclohexylphosphine-2 ',4',6 '-triisopropylbiphenyl, 2-dicyclohexylphosphine-2', 6 '-dimethoxy-1, 1' -biphenyl, 4, 5-bis (diphenylphosphino) -9, 9-dimethylxanthene, bis (2-diphenylphosphinophenyl) ether and/or 4, 5-bis-diphenylphosphino-9, 9-dimethylxanthene.
5. The process according to claim 3, wherein the molar ratio of the compound of the formula (II) to the catalyst based on the component A is 1 (0.001-0.5); the molar ratio is preferably 1 (0.001-0.01).
6. The method according to claim 1, wherein the basic substance is one or more of sodium hydroxide, potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, DBU, DIPEA, triethylamine, and pyridine.
Preferably, the basic substance is one or more of sodium hydroxide, potassium carbonate, sodium bicarbonate, cesium carbonate, DBU and triethylamine.
Preferably, the molar ratio of the compound represented by the general formula (II) to the basic substance is 1 (1-3), and preferably 1 (1-2).
7. The method of claim 1, wherein the acidification employs at least one of hydrochloric acid, sulfuric acid, and acetic acid; preferably, hydrochloric acid or sulfuric acid is used for acidification.
Preferably, the acidification step is to adjust the pH to 2-3 with an acid.
8. The method according to claim 1, wherein the solvent is one or more selected from the group consisting of dichloroethane, acetonitrile, diethyl ether, toluene, chlorobenzene, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, NMP, DMF, and DMSO.
Preferably, the solvent is selected from one or more of acetonitrile, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, toluene and DMF.
9. The method according to claim 1, wherein the reaction conditions are as follows:
the reaction pressure is: 2 to 10MPa, for example 3 to 8MPa, 5 to 8MPa, 4 to 6 MPa;
the reaction temperature is as follows: 90-180 ℃, such as 100-160 ℃, 120-150 ℃;
the reaction time is as follows: from 0.2 to 48 hours, for example from 0.5 to 40 hours; 1-36 hours, 2-30 hours, 3-24 hours, 4-20 hours and 5-12 hours.
Specifically, the compound shown in the general formula (II) and the compound shown in the general formula (III) are dissolved in acetonitrile solvent, nitrogen monoxide gas is introduced into a reaction kettle for replacement for 3 times, then carbon monoxide gas is introduced for replacement for 2 times, then the pressure of the reaction kettle is increased to 5.0Mpa, stirring is started, the temperature is increased to 150 ℃, and the reaction is carried out for 20 hours under the condition of heat preservation.
10. A preparation method of pyrazole compounds shown in formula (1), formula (5) and formula (7) is characterized in that the reaction is as follows in sequence:
Figure FDA0003633460550000041
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