CN115433129B - Process for preparing pyrazoles - Google Patents
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- CN115433129B CN115433129B CN202110615731.7A CN202110615731A CN115433129B CN 115433129 B CN115433129 B CN 115433129B CN 202110615731 A CN202110615731 A CN 202110615731A CN 115433129 B CN115433129 B CN 115433129B
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- 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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Abstract
The invention relates to the technical field of herbicide preparation, and discloses a method for preparing pyrazole compounds. The method of the invention comprises the following steps: in the presence of a first solvent and a first alkaline substance, carrying out ring-closure reaction on a compound shown in a formula (II) and methyl hydrazine to obtain a compound shown in a formula (I); wherein, in the compounds shown in the formula (I) and the formula (II), R is C1-C6 alkyl, and X is F, cl, br or I. In the method, the compound shown in the formula (II) is used as a starting material, the ring closure reaction with methyl hydrazine is carried out efficiently, almost no side reaction occurs, the selectivity and the yield are high, and the prepared pyrazole compound (pyrazole herbicide intermediate) has high purity. In addition, the method provided by the invention has mild reaction conditions, and the related reagents are safe and have low cost.
Description
Technical Field
The invention relates to the technical field of herbicide preparation, in particular to a method for preparing pyrazole compounds.
Background
The topramezone is a herbicide with good effect, is the first benzyl ester pyrazolone herbicide developed by basf, also belongs to a p-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has good preventing and killing effect on weeds with glyphosate resistance, triazines, acetolactate synthase (ALS) inhibitor and acetyl coenzyme A carboxylase inhibitor, and can prevent and kill main gramineous weeds and broadleaf weeds on corn crops worldwide. Therefore, the synthesis research of phenylpyrazole compounds is receiving much attention.
The phenylpyrazole compound is generally prepared from an intermediate 1-methyl-5-hydroxypyrazole. CN105218449, IN201611027903, WO2017075910, WO2009069044, CN111440160A and the like disclose a preparation method of 1-methyl-5 hydroxypyrazole, which is prepared by the following two ways:
a：
b：
in the prior art, diethyl malonate or analogues are reacted with triethyl orthoformate or methyl ester or acetic anhydride, and then the reaction product is subjected to ring closure with methyl hydrazine, and hydrolysis and decarboxylation are carried out to prepare the topramezone intermediate 1-methyl-5 hydroxypyrazole; or diethyl oxaloacetate and methyl hydrazine are adopted for closing the ring, and hydrolysis and decarboxylation are carried out to prepare the topramezone intermediate 1-methyl-5-hydroxypyrazole. However, these two methods have the defects of low yield due to poor selectivity when the two methods are used for ring-closing reaction with methyl hydrazine, and the high yield of 1-methyl-4-hydroxypyrazole, as well as the high corrosiveness and difficult recovery of acetic anhydride and byproducts thereof in the diethyl malonate process, and the high consumption and high price of triethyl orthoformate (or methyl ester), thus being unfavorable for industrial production.
Disclosure of Invention
The invention aims to overcome the technical problems in the prior art and provides a method for preparing pyrazole compounds. The method has the advantages of higher selectivity and yield, and the prepared pyrazole compound (pyrazole herbicide intermediate) has higher purity.
In order to achieve the above object, the present invention provides a method for producing a pyrazole compound, comprising: in the presence of a first solvent and a first alkaline substance, carrying out ring-closure reaction on a compound shown in a formula (II) and methyl hydrazine to obtain a compound shown in a formula (I); wherein, in the compounds shown in the formula (I) and the formula (II), R is C1-C6 alkyl, and X is F, cl, br or I.
Compared with the prior art, the method adopts the compound shown in the formula (II) as the starting material, and performs the ring-closure reaction with methyl hydrazine with high efficiency, and almost no side reaction occurs, so that the selectivity, the yield and the purity of the target compound are high, and further, the compound shown in the formula (II) is hydrolyzed and decarboxylated in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole with high purity in high yield. In addition, the method provided by the invention has mild reaction conditions, the related reagents are safe and low in cost, and part of materials can be recycled, so that the cost is further reduced.
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
The invention provides a method for preparing a pyrazole herbicide intermediate, which comprises the following steps: in the presence of a first solvent and a first alkaline substance, carrying out ring-closure reaction on a compound shown in a formula (II) and methyl hydrazine to obtain a compound shown in a formula (I); wherein, in the compounds shown in the formula (I) and the formula (II), R is C1-C6 alkyl, and X is F, cl, br or I.
According to some embodiments of the invention, in the compounds of formula (I) and formula (II), R is methyl or ethyl and X is Cl or Br.
In the present invention, the compound represented by the formula (II) may be obtained commercially or may be prepared by referring to a conventional manner in the art. For example, the following procedure (for example, the preparation of diethyl 2-chloro-2-butenedioate) may be used: mixing diethyl maleate, a second solvent (such as N, N-dimethylformamide) and a second alkaline substance (such as potassium carbonate), heating to 45-60 ℃, introducing chlorine into the system, reacting at 45-60 ℃ for 0.5-2h under heat preservation, and removing the second solvent from the reacted system under reduced pressure at 70-90 ℃ and 0.05-0.095 MPa to obtain the compound shown in the formula (II). Wherein, the mol ratio of the diethyl maleate to the second alkaline substance to the chlorine is 1: (1.05-1.2): (1.3-1.8). Preferably, the chlorine gas is introduced at a rate of 0.3 to 0.6g/min relative to 0.2mol of diethyl maleate. Preferably, the second solvent is used in an amount of 80 to 120g with respect to 0.2mol of diethyl maleate.
According to some embodiments of the invention, the conditions of the ring closure reaction may include: the temperature is-20deg.C to 100deg.C (20 deg.C, -10deg.C, 0 deg.C, 10 deg.C, 20 deg.C, 30 deg.C, 40 deg.C, 50 deg.C, 60 deg.C, 70 deg.C, 80 deg.C, 90 deg.C, 100 deg.C or any value between the above values), preferably-10deg.C to 60deg.C; the time is 1-10 hours, preferably 4-7 hours.
According to some embodiments of the present invention, the molar ratio of the compound of formula (II), methyl hydrazine, and the first basic substance may be 1: (1-1.5): (1.1-2), preferably 1: (1.05-1.2): (1.1-1.3).
According to some embodiments of the invention, the first basic substance may be selected from one of sodium methoxide, sodium ethoxide, N-diisopropylethylamine, triethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate, N-dimethylaniline, preferably from sodium methoxide and/or potassium carbonate.
According to some embodiments of the present invention, the first solvent may be selected from at least one of C6-C8 alkanes, C1-C4 halogenated hydrocarbons, C6-C10 aromatic hydrocarbons, C1-C4 monohydric alcohols, C2-C6 oxygenated naphthenic hydrocarbons, and N, N-dimethylformamide, preferably from at least one of cyclohexane, dichloromethane, dichloroethane, toluene, methanol, ethanol, tetrahydrofuran, propylene oxide, 1, 2-butylene oxide, and N, N-dimethylformamide, more preferably from at least one of methanol, cyclohexane, and dichloroethane.
According to some embodiments of the present invention, the first solvent may be used in an amount of 0.5 to 10g, preferably 1 to 5g, per gram of the compound represented by formula (II).
In the present invention, methyl hydrazine is preferably present in the form of an aqueous solution; wherein the concentration of the aqueous solution of methyl hydrazine is preferably 30 to 50wt%.
In the present invention, in order to obtain a better effect, in the step (1), the addition of the compound represented by the formula (II), the first solvent and the methylhydrazine is preferably performed in the following manner: the compound shown in the formula (II) and the first solvent are mixed, the obtained mixture is heated to 25-40 ℃, a first alkaline substance is added into the mixture, then an aqueous solution of methyl hydrazine (with the concentration of 30-50 wt%) is added into the system, and then the ring closure reaction is carried out under the condition of heat preservation at 25-40 ℃. Wherein the methyl hydrazine is added at a rate of 0.1 to 1mol/h relative to 1mol of the compound represented by the formula (II).
In the present invention, the mode of post-treatment in step (1) is not particularly limited as long as the requirements of the present invention can be satisfied. For example, this can be done in the following way: and (3) decompressing and removing the first solvent from the reacted system at the temperature of less than or equal to 80 ℃ (preferably 30-80 ℃) and the pressure of 0.05-0.095 MPa to obtain the compound shown in the formula (I).
According to some embodiments of the invention, the method further comprises the steps of:
subjecting a compound represented by the formula (I) to hydrolytic decarboxylation in the presence of an acid to obtain 1-methyl-5-hydroxypyrazole (compound represented by the formula (III)),
according to some embodiments of the invention, in step (1), the conditions of the ring closure reaction may include: the temperature is between minus 10 ℃ and 60 ℃; the time is 4-7h;
the molar ratio of the compound shown in the formula (II), methyl hydrazine and the first alkaline substance is 1: (1.05-1.2): (1.1-1.3);
the first alkaline substance is selected from sodium methoxide and/or potassium carbonate;
the first solvent is selected from at least one of methanol, cyclohexane and dichloroethane;
the first solvent is used in an amount of 1 to 5g per gram of the compound represented by the formula (II).
According to some embodiments of the invention, in step (2), the conditions of hydrolytic decarboxylation may include: the temperature is 30-150deg.C, preferably 60-140deg.C, and further preferably 60-90deg.C; the time is 1-10 hours, preferably 4-7 hours.
According to some embodiments of the invention, the molar ratio of the compound of formula (I) to the acid may be 1: (1-5), preferably 1: (2-3).
According to some embodiments of the invention, the acid is an inorganic acid, preferably at least one selected from hydrochloric acid, sulfuric acid and hydrobromic acid, more preferably selected from hydrochloric acid and/or sulfuric acid.
According to some embodiments of the invention, the hydrolytic decarboxylation is performed in the presence of a third solvent selected from at least one of C6-C8 alkanes, C1-C4 halogenated hydrocarbons, C6-C10 aromatic hydrocarbons, C2-C6 oxacycloalkanes, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone and toluene, preferably selected from at least one of N, N-Dimethylformamide (DMF), N-Dimethylacetamide (DMA) and toluene.
According to some embodiments of the invention, the third solvent is used in an amount of 0.2 to 10g, preferably 0.5 to 3g, per gram of the compound of formula (I).
In the present invention, the post-treatment in step (2) is not particularly limited as long as the requirements of the present invention can be satisfied. For example, reference may be made to the following: removing the third solvent from the reacted system, adding an organic solvent (preferably C1-C4 alcohol such as ethanol), pulping and filtering to obtain a filter cake; namely the product (1-methyl-5-hydroxypyrazole). The amount of the organic solvent used for beating is not particularly limited, but may be preferably 0.5 to 3g relative to 1g of the compound represented by the formula (I).
The present invention will be described in detail by examples.
In the following examples, the raw materials, solvents, bases, etc. used were all commercially available without particular explanation; the progress of the reaction and the purity of the product were monitored by HPLC (high performance liquid chromatography); the yield was calculated as actual product molar amount/theoretical product molar amount x 100%.
Example 1
In this embodiment, x=cl, r=et
(1) 41.2g (0.2 mol) of the compound shown in the formula (II) and 100g of methanol are sequentially added into a 250mL four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, after the temperature is raised to 30 ℃, 11.88g (0.22 mol) of sodium methoxide is added, 25.3g (0.22 mol,40 wt%) of aqueous solution of methylhydrazine is dropwise added into the system, after the dropwise addition is completed within 3 hours, the temperature is kept at 30 ℃ for ring closing reaction for 4 hours, HPLC monitoring reaction is complete, methanol is removed under reduced pressure at 50 ℃ and 0.07MPa, and the compound shown in the formula (I) is obtained with the purity of 99 wt% and the yield of 98%.
(2) 50g of DMF and 56g of sulfuric acid (70 wt%,0.4 mol) were added to the compound represented by the formula (I) obtained above, the temperature was raised to 60℃to carry out hydrolysis and decarboxylation for 8 hours, after removal of DMF, 40g of ethanol was added to the system after the reaction to carry out beating filtration, and filter cake 1-methyl-5-hydroxypyrazole was obtained with a purity of 96 wt% and a yield of 95%.
Example 2
In this embodiment, x=cl, r=et
(1) 41.2g (0.2 mol) of diethyl 2-chloro-2-butene-dioate and 100g of methylene chloride are sequentially added into a four-port bottle with 250mL of a mechanical stirring, a thermometer and a condenser, 30.36g (0.22 mol) of potassium carbonate is added after the temperature is raised to 30 ℃, 24.15g (0.21 mol,40 wt%) of aqueous solution of methylhydrazine is dropwise added into the system, the dropwise addition is completed within 3h, the temperature is kept at 30 ℃ for carrying out a ring closing reaction for 4h, HPLC monitoring reaction is complete, methylene chloride is removed under reduced pressure at 30 ℃ under 0.05MPa, and the compound shown in the formula (I) is obtained, the purity is 98.5 wt% and the yield is 97.5%.
(2) 50g of DMF and 56g of sulfuric acid (70 wt%,0.4 mol) were added to the compound represented by the formula (I) obtained above, the temperature was raised to 70℃to carry out hydrolysis and decarboxylation for 8 hours, after removal of DMF, 40g of ethanol was added to the system after the reaction to carry out beating filtration, and filter cake 1-methyl-5-hydroxypyrazole was obtained with a purity of 95.5 wt% and a yield of 94%.
Example 3
In this embodiment, x=cl, r=et
(1) 41.2g (0.2 mol) of diethyl 2-chloro-2-butene-dioate and 100g of tetrahydrofuran are sequentially added into a four-necked flask which is provided with mechanical stirring, a thermometer and a condenser, 30.36g (0.22 mol) of potassium carbonate is added after the temperature is raised to 30 ℃, 25.3g (0.22 mol,40 wt%) of aqueous solution of methylhydrazine is dropwise added into the system, the dropwise addition is completed within 3 hours, the temperature is kept at 30 ℃ for carrying out a ring closing reaction for 4 hours, HPLC monitoring reaction is complete, tetrahydrofuran is removed under reduced pressure at 60 ℃ under 0.075MPa, and the compound shown in the formula (I) is obtained with the purity of 99 wt% and the yield of 98%.
(2) 50g of toluene and 56g of sulfuric acid (70 wt%,0.4 mol) were added to the compound represented by the above-obtained formula (I), the temperature was raised to 80℃to carry out hydrolysis and decarboxylation for 8 hours, and after removing toluene, 40g of ethanol was added to the system after the reaction to carry out beating filtration, to obtain a cake of 1-methyl-5-hydroxypyrazole having a purity of 96.5 wt% and a yield of 96%.
Example 4
In this embodiment, x=cl, r=et
41.2g (0.2 mol) of the compound shown in the formula (II) and 100g of toluene are sequentially added into a 250mL four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, the temperature is raised to 100 ℃, 11.88g (0.22 mol) of sodium methoxide is added, 25.3g (0.22 mol,40 wt%) of aqueous solution of methylhydrazine is dropwise added into the system, the solution is kept at 100 ℃ for ring closing reaction for 4 hours after 3 hours dropwise addition, HPLC monitoring reaction is complete, toluene is removed under reduced pressure at 80 ℃ and 0.095MPa, and the compound shown in the formula (I) is obtained with the purity of 80 wt% and the yield of 78%.
Example 5
The procedure of example 1 was followed, except that the temperature of the ring-closing reaction was changed to-20 ℃.
In this embodiment, x=cl, r=et
(1) 41.2g (0.2 mol) of the compound shown in the formula (II) and 100g (0.22 mol) of methanol are sequentially added into a 250mL four-necked flask provided with a mechanical stirrer, a thermometer and a condenser, the temperature is reduced to minus 20 ℃, 11.88g (0.22 mol) of sodium methoxide is added, 25.3g (0.22 mol,40 wt%) of aqueous solution of methylhydrazine is dropwise added into the system, the reaction is closed by heat preservation at minus 20 ℃ for 4 hours after the dropwise addition is completed, the reaction is monitored completely by HPLC, the methanol is removed under reduced pressure at 50 ℃ and 0.07MPa, and the compound shown in the formula (I) is obtained with the purity of 95 wt% and the yield of 90%.
Example 6
In this embodiment, x=cl, r=et
The procedure of example 1 was followed, except that the compound of formula (II), the first solvent, the first basic substance and methylhydrazine were simultaneously added during the ring-closing reaction, and that methylhydrazine (aqueous solution of methylhydrazine) was not used in the form of dropwise addition.
(1) 41.2g (0.2 mol) of the compound shown in the formula (II) (diethyl 2-chloro-2-butenedioic acid), 100g of methanol and 25.3g (0.22 mol,40 wt%) of aqueous solution of methylhydrazine are simultaneously added into a 250mL four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, the reaction is closed by heat preservation at 30 ℃ for 4 hours, the reaction is complete by HPLC monitoring, and methanol is removed under reduced pressure at 50 ℃ and 0.07MPa, so that the compound shown in the formula (I) is obtained with the purity of 92 wt% and the yield of 87%.
Comparative example 1
The preparation method of the 1-methyl-5-hydroxypyrazole by referring to the existing method comprises the following specific steps:
into a 500mL four-port bottle equipped with a mechanical stirrer, a thermometer and a condenser tube, 0.2mol of diethyl malonate 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, then the reflux temperature is reduced to 104 ℃, and the content of diethyl malonate in the gas chromatograph is controlled to be less than 1 percent (the peak area ratio of diethyl malonate is less than 1 percent). The acetic acid mixture is distilled off under reduced pressure to 110 ℃, the temperature is reduced to 10 ℃, and 120g of absolute methanol is added. Stirring and controlling the reaction temperature to 10 ℃, dropwise adding aqueous solution (0.33 mol,40 wt%) of methyl hydrazine, reacting for 4 hours at 25 ℃ after the addition is completed, decompressing and removing methanol, adding 120g of sulfuric acid (0.2 mol,70 wt%) and 120g of N, N-dimethylformamide, heating to 85 ℃ for hydrolysis and decarboxylation for 7 hours, adding 40g of ethanol into the removed solvent, pulping and filtering, and refining to obtain the phenylpyrazole herbicide intermediate (1-methyl-5-hydroxypyrazole).
The purity of 1-methyl-5-hydroxypyrazole was 93 wt% and the yield was 71% by detection and calculation.
In the comparative example, in the ring closing reaction, the isomer 1-methyl-4 hydroxy pyrazole is generated, the influence on the yield is large, acetic anhydride is used in the method, a large amount of acetic acid byproducts are generated, the acetic acid byproducts are difficult to treat, and the environment is not easy to protect.
Comparative example 2
The preparation method of the 1-methyl-5-hydroxypyrazole by referring to the existing method comprises the following specific steps:
56.4g (0.3 mol) of diethyl oxaloacetate, 150g of ethanol, 37.95g (0.33 mol,40 wt%) of methyl hydrazine aqueous solution at 25 ℃ are added into a 500mL four-necked flask equipped with a mechanical stirrer, a thermometer and a condenser, the mixture is stirred at a constant temperature after the dripping, the mixture is subjected to ring closure for 5 hours, 84g (0.6 mol,70 wt%) of sulfuric acid is distilled out under reduced pressure, 120g of N, N-dimethylacetamide is added, the mixture is heated to 70 ℃ for hydrolysis and decarboxylation for 5 hours, and 30g of ethanol is added after the solvent is removed, the mixture is pulped and filtered to obtain 1-methyl-5-hydroxypyrazole.
The purity of the obtained product phenylpyrazole herbicide intermediate (1-methyl-5-hydroxypyrazole) is 92 weight percent and the yield is 74 percent through detection and calculation.
Compared with the prior art, the method provided by the invention can obtain the pyrazole herbicide intermediate with higher purity and yield, and in a preferred embodiment, the purity of the pyrazole herbicide intermediate prepared by the method can reach more than 95 weight percent, and the yield can reach more than 93 percent. In addition, as can be seen from the above embodiments, the method of the present invention has the advantages of safety, simplicity and low cost.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.
Claims (51)
1. A process for preparing pyrazoles, characterized in that the process comprises: in the presence of a first solvent and a first alkaline substance, carrying out ring-closure reaction on a compound shown in a formula (II) and methyl hydrazine to obtain a compound shown in a formula (I); wherein, in the compounds shown in the formula (I) and the formula (II), R is C1-C6 alkyl, X is F, cl, br or I;
2. the method according to claim 1, wherein in the compounds represented by the formula (I) and the formula (II), R is methyl or ethyl, and X is Cl or Br.
3. The method of claim 1 or 2, wherein the conditions of the ring closure reaction comprise: the temperature is between-20 ℃ and 100 ℃ and the time is between 1 and 10 hours.
4. A method according to claim 3, wherein the conditions of the ring closure reaction comprise: the temperature is-10 ℃ to 60 ℃ and the time is 4-7h.
5. The method according to any one of claims 1,2, and 4, wherein the molar ratio of the compound represented by formula (II), methyl hydrazine, and the first basic substance is 1: (1-1.5): (1.1-2).
6. The method according to claim 5, wherein the molar ratio of the compound represented by formula (II), methyl hydrazine, and the first basic substance is 1: (1.05-1.2): (1.1-1.3).
7. A method according to claim 3, wherein the molar ratio of the compound of formula (II), methyl hydrazine and the first basic substance is 1: (1-1.5): (1.1-2).
8. The method according to claim 7, wherein the molar ratio of the compound represented by formula (II), methyl hydrazine, and the first basic substance is 1: (1.05-1.2): (1.1-1.3).
9. The method of any one of claims 1,2, 4, 6-8, wherein the first basic substance is selected from one of sodium methoxide, sodium ethoxide, N-diisopropylethylamine, triethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate, N-dimethylaniline.
10. The method of claim 9, wherein the first alkaline substance is selected from sodium methoxide and/or potassium carbonate.
11. A method according to claim 3, wherein the first basic substance is selected from one of sodium methoxide, sodium ethoxide, N-diisopropylethylamine, triethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate, N-dimethylaniline.
12. The method of claim 11, wherein the first alkaline substance is selected from sodium methoxide and/or potassium carbonate.
13. The method according to claim 5, wherein the first basic substance is selected from one of sodium methoxide, sodium ethoxide, N-diisopropylethylamine, triethylamine, pyridine, sodium carbonate, potassium carbonate, sodium formate, sodium acetate, potassium acetate, N-dimethylaniline.
14. The method of claim 13, wherein the first alkaline substance is selected from sodium methoxide and/or potassium carbonate.
15. The method of any one of claims 1,2, 4, 6-8, 10-14, wherein the first solvent is selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C1-C4 monohydric alcohol, a C2-C6 oxacycloalkane, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 0.5 to 10g per gram of the compound represented by formula (II).
16. The method of claim 15, wherein the first solvent is selected from at least one of cyclohexane, dichloromethane, dichloroethane, toluene, methanol, ethanol, tetrahydrofuran, propylene oxide, 1, 2-butylene oxide, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 1 to 5g per gram of the compound represented by formula (II).
17. The method of claim 16, wherein the first solvent is selected from at least one of methanol, cyclohexane, dichloroethane.
18. The method of claim 3, wherein the first solvent is selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C1-C4 monohydric alcohol, a C2-C6 oxacycloalkane, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 0.5 to 10g per gram of the compound represented by formula (II).
19. The method of claim 18, wherein the first solvent is selected from at least one of cyclohexane, dichloromethane, dichloroethane, toluene, methanol, ethanol, tetrahydrofuran, propylene oxide, 1, 2-butylene oxide, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 1 to 5g per gram of the compound represented by formula (II).
20. The method of claim 19, wherein the first solvent is selected from at least one of methanol, cyclohexane, dichloroethane.
21. The method of claim 5, wherein the first solvent is selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C1-C4 monohydric alcohol, a C2-C6 oxacycloalkane, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 0.5 to 10g per gram of the compound represented by formula (II).
22. The method of claim 21, wherein the first solvent is selected from at least one of cyclohexane, dichloromethane, dichloroethane, toluene, methanol, ethanol, tetrahydrofuran, propylene oxide, 1, 2-butylene oxide, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 1 to 5g per gram of the compound represented by formula (II).
23. The method of claim 22, wherein the first solvent is selected from at least one of methanol, cyclohexane, dichloroethane.
24. The method of claim 9, wherein the first solvent is selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C1-C4 monohydric alcohol, a C2-C6 oxacycloalkane, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 0.5 to 10g per gram of the compound represented by formula (II).
25. The method of claim 24, wherein the first solvent is selected from at least one of cyclohexane, dichloromethane, dichloroethane, toluene, methanol, ethanol, tetrahydrofuran, propylene oxide, 1, 2-butylene oxide, and N, N-dimethylformamide;
and/or the first solvent is used in an amount of 1 to 5g per gram of the compound represented by formula (II).
26. The method of claim 25, wherein the first solvent is selected from at least one of methanol, cyclohexane, dichloroethane.
27. The method of any one of claims 1,2, 4, 6-8, 10-14, 16-26, wherein the method further comprises: the compound shown in the formula (I) is subjected to hydrolytic decarboxylation in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole.
28. A method according to claim 3, wherein the method further comprises: the compound shown in the formula (I) is subjected to hydrolytic decarboxylation in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole.
29. The method of claim 5, wherein the method further comprises: the compound shown in the formula (I) is subjected to hydrolytic decarboxylation in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole.
30. The method of claim 9, wherein the method further comprises: the compound shown in the formula (I) is subjected to hydrolytic decarboxylation in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole.
31. The method of claim 15, wherein the method further comprises: the compound shown in the formula (I) is subjected to hydrolytic decarboxylation in the presence of acid to obtain the 1-methyl-5-hydroxypyrazole.
32. The method of any one of claims 28-31, wherein the conditions of the ring closure reaction comprise: the temperature is between-10 ℃ and 60 ℃ and the time is between 4 and 7 hours;
the molar ratio of the compound shown in the formula (II), methyl hydrazine and the first alkaline substance is 1: (1.05-1.2): (1.1-1.3);
the first alkaline substance is selected from sodium methoxide and/or potassium carbonate;
the first solvent is selected from at least one of methanol, cyclohexane and dichloroethane;
the first solvent is used in an amount of 1 to 5g per gram of the compound represented by the formula (II).
33. The method of claim 27, wherein the conditions of the ring closure reaction comprise: the temperature is between-10 ℃ and 60 ℃ and the time is between 4 and 7 hours;
the molar ratio of the compound shown in the formula (II), methyl hydrazine and the first alkaline substance is 1: (1.05-1.2): (1.1-1.3);
the first alkaline substance is selected from sodium methoxide and/or potassium carbonate;
the first solvent is selected from at least one of methanol, cyclohexane and dichloroethane;
the first solvent is used in an amount of 1 to 5g per gram of the compound represented by the formula (II).
34. The method of any one of claims 28-31, 33, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 30-150 ℃ and the time is 1-10h.
35. The method of claim 34, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 60-140 ℃ and the time is 4-7h.
36. The method of claim 27, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 30-150 ℃ and the time is 1-10h.
37. The method of claim 36, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 60-140 ℃ and the time is 4-7h.
38. The method of claim 32, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 30-150 ℃ and the time is 1-10h.
39. The method of claim 38, wherein the conditions of hydrolytic decarboxylation comprise: the temperature is 60-140 ℃ and the time is 4-7h.
40. The method of any one of claims 28-31, 33, 35-39, wherein the molar ratio of the compound of formula (I) to the acid is 1: (1-5);
and/or the acid is an inorganic acid;
and/or the hydrolytic decarboxylation is performed in the presence of a third solvent selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C2-C6 oxacycloalkane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and toluene.
41. The process of claim 40, wherein the molar ratio of the compound of formula (I) to the acid is 1: (2-3);
and/or the acid is selected from at least one of hydrochloric acid, sulfuric acid and hydrobromic acid;
and/or the third solvent is selected from at least one of N, N-dimethylformamide, N-dimethylacetamide and toluene;
and/or the third solvent is used in an amount of 0.2 to 10g per gram of the compound represented by formula (I).
42. The method of claim 41, wherein the acid is selected from hydrochloric acid and/or sulfuric acid;
and/or the third solvent is used in an amount of 0.5 to 3g per gram of the compound represented by formula (I).
43. The method of claim 27, wherein the molar ratio of the compound of formula (I) to the acid is 1: (1-5);
and/or the acid is an inorganic acid;
and/or the hydrolytic decarboxylation is performed in the presence of a third solvent selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C2-C6 oxacycloalkane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and toluene.
44. The process of claim 43, wherein the molar ratio of the compound of formula (I) to the acid is 1: (2-3);
and/or the acid is selected from at least one of hydrochloric acid, sulfuric acid and hydrobromic acid;
and/or the third solvent is selected from at least one of N, N-dimethylformamide, N-dimethylacetamide and toluene;
and/or the third solvent is used in an amount of 0.2 to 10g per gram of the compound represented by formula (I).
45. The method of claim 44, wherein the acid is selected from hydrochloric acid and/or sulfuric acid;
and/or the third solvent is used in an amount of 0.5 to 3g per gram of the compound represented by formula (I).
46. The method of claim 32, wherein the molar ratio of the compound of formula (I) to the acid is 1: (1-5);
and/or the acid is an inorganic acid;
and/or the hydrolytic decarboxylation is performed in the presence of a third solvent selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C2-C6 oxacycloalkane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and toluene.
47. The method of claim 46, wherein the molar ratio of the compound of formula (I) to the acid is 1: (2-3);
and/or the acid is selected from at least one of hydrochloric acid, sulfuric acid and hydrobromic acid;
and/or the third solvent is selected from at least one of N, N-dimethylformamide, N-dimethylacetamide and toluene;
and/or the third solvent is used in an amount of 0.2 to 10g per gram of the compound represented by formula (I).
48. The method of claim 47, wherein the acid is selected from hydrochloric acid and/or sulfuric acid;
and/or the third solvent is used in an amount of 0.5 to 3g per gram of the compound represented by formula (I).
49. The method of claim 34, wherein the molar ratio of the compound of formula (I) to the acid is 1: (1-5);
and/or the acid is an inorganic acid;
and/or the hydrolytic decarboxylation is performed in the presence of a third solvent selected from at least one of a C6-C8 alkane, a C1-C4 halogenated hydrocarbon, a C6-C10 aromatic hydrocarbon, a C2-C6 oxacycloalkane, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, and toluene.
50. The process of claim 49, wherein the molar ratio of the compound of formula (I) to the acid is 1: (2-3);
and/or the acid is selected from at least one of hydrochloric acid, sulfuric acid and hydrobromic acid;
and/or the third solvent is selected from at least one of N, N-dimethylformamide, N-dimethylacetamide and toluene;
and/or the third solvent is used in an amount of 0.2 to 10g per gram of the compound represented by formula (I).
51. The method of claim 50, wherein the acid is selected from hydrochloric acid and/or sulfuric acid;
and/or the third solvent is used in an amount of 0.5 to 3g per gram of the compound represented by formula (I).
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