CN117986190B - Method for synthesizing ethyl trimethylpyrazole - Google Patents
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- CN117986190B CN117986190B CN202410396964.6A CN202410396964A CN117986190B CN 117986190 B CN117986190 B CN 117986190B CN 202410396964 A CN202410396964 A CN 202410396964A CN 117986190 B CN117986190 B CN 117986190B
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- 238000000034 method Methods 0.000 title claims abstract description 29
- -1 ethyl trimethylpyrazole Chemical compound 0.000 title claims abstract description 21
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 20
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 20
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims abstract description 15
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 9
- 239000008367 deionised water Substances 0.000 claims abstract description 4
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 10
- BKLPCUANPRARSC-UHFFFAOYSA-N 5-ethyl-1,3,4-trimethylpyrazole Chemical compound CCC1=C(C)C(C)=NN1C BKLPCUANPRARSC-UHFFFAOYSA-N 0.000 claims description 7
- 238000009835 boiling Methods 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000001308 synthesis method Methods 0.000 claims description 2
- GIUTUZDGHNZVIA-UHFFFAOYSA-N 2-(ethylamino)acetic acid;hydrochloride Chemical compound Cl.CCNCC(O)=O GIUTUZDGHNZVIA-UHFFFAOYSA-N 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 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 abstract description 5
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 abstract description 5
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 4
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 abstract description 3
- 231100000086 high toxicity Toxicity 0.000 abstract description 3
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000012824 chemical production Methods 0.000 abstract description 2
- 238000010924 continuous production Methods 0.000 abstract description 2
- 238000006193 diazotization reaction Methods 0.000 abstract description 2
- 238000004821 distillation Methods 0.000 abstract description 2
- 239000002360 explosive Substances 0.000 abstract description 2
- CRBDHJDPBLYJHY-UHFFFAOYSA-N Cl.C(C)(=O)OCC.NCC(=O)O Chemical compound Cl.C(C)(=O)OCC.NCC(=O)O CRBDHJDPBLYJHY-UHFFFAOYSA-N 0.000 abstract 1
- 239000012043 crude product Substances 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 13
- WUUUUWIHHKLIHO-UHFFFAOYSA-N ethyl 2,4,5-trimethylpyrazole-3-carboxylate Chemical compound CCOC(=O)C1=C(C)C(C)=NN1C WUUUUWIHHKLIHO-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- WOPRYIVMIKGIGV-UHFFFAOYSA-N 2,4,5-trimethylpyrazole-3-carboxylic acid Chemical compound CC1=NN(C)C(C(O)=O)=C1C WOPRYIVMIKGIGV-UHFFFAOYSA-N 0.000 description 1
- IVLXQGJVBGMLRR-UHFFFAOYSA-N 2-aminoacetic acid;hydron;chloride Chemical compound Cl.NCC(O)=O IVLXQGJVBGMLRR-UHFFFAOYSA-N 0.000 description 1
- LTWANVXGOGHTRX-UHFFFAOYSA-N 5-(2,2-dimethylpropyl)-1h-pyrazole Chemical compound CC(C)(C)CC=1C=CNN=1 LTWANVXGOGHTRX-UHFFFAOYSA-N 0.000 description 1
- 238000003512 Claisen condensation reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229960001269 glycine hydrochloride Drugs 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, and in particular provides a method for synthesizing ethyl trimethylpyrazole, which comprises the steps of adding glycine ethyl acetate hydrochloride, deionized water, sodium nitrite and sulfuric acid into a reaction bottle according to a certain proportion, adding 2-butanone and dimethyl carbonate according to a certain proportion after reaction, extracting to obtain a crude product after reaction, and then carrying out reduced pressure distillation to obtain the ethyl 1,3, 4-trimethyl-5-pyrazole. On one hand, the invention avoids flammable and explosive dangerous processes such as direct diazotization, hydrogenation and the like, and is safe to operate; on the other hand, high-toxicity raw materials such as hydrazine hydrate, methyl hydrazine, ethyl diazoacetate and the like are not used, so that the method is more suitable for a green continuous production process, and accords with the current green safe chemical production concept.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing ethyl trimethylpyrazole.
Background
Ethyl 1,3, 4-trimethyl-5-pyrazolate is an important intermediate compound. Wherein, 1,3, 4-trimethyl-5-pyrazol acid ethyl ester is an important initial synthetic raw material in the synthesis of the insecticidal and acaricidal agent-cyenopyrafen. In a common method, acetone is used as a starting material, and 1,3, 4-trimethyl-5-ethyl pyrazole is obtained through the steps of Claisen reaction, knorr cyclization reaction, methylation, chlorination, hydrogenation reduction and the like. The route has more operation steps, complicated operation and low comprehensive yield, and is not beneficial to reducing industrial cost and large-scale production.
In the prior patent, for example, in patent CN112824393, oxalic acid diester and butanone are used as starting materials, and under the action of a catalyst, the 1,3, 4-trimethyl-5-ethyl pyrazole is obtained through hydrazine hydrate or methyl hydrazine reaction. The method needs hydrazine hydrate or methyl hydrazine with relatively high cost as raw materials, and the hydrazine hydrate and the methyl hydrazine have high toxicity, and the product obtained after the two-step reaction has poor structural selectivity, more impurities and difficult separation; in addition, according to patent CN114478387, ethyl diazoacetate is used as a starting material, and reacts with butanone under the catalysis of copper salt, and 1,3, 4-trimethyl-5-pyrazolate ethyl ester is obtained through methylation step.
Therefore, a synthetic method of trimethyl ethyl pyrazole acid ester for synthesizing 1,3, 4-trimethyl-5-ethyl pyrazole acid ester is needed by a process route which is simple and safe to operate, high in yield and green and low in toxicity.
Disclosure of Invention
In order to solve the problems, the invention aims to provide a method for synthesizing ethyl trimethylpyrazole.
The invention provides a method for synthesizing ethyl trimethylpyrazole, which comprises the following steps:
Step one: 1.39-13.9 g of glycine ethyl ester hydrochloride is added into a 50mL round bottom flask, 20mL of deionized water is added, and stirring is carried out for 30min at 25 ℃;
Step two: adding 0.7-14 g of sodium nitrite, dropwise adding 1-5 ml of sulfuric acid with the concentration of 5mol/L, and stirring for 1h at 25 ℃;
Step three: 2-butanone with the amount of 1-5 times of glycine ethyl ester hydrochloride substances is dropwise added, and the reaction is carried out for 8-24 hours under the condition of heat preservation;
Step four: and dropwise adding dimethyl carbonate with the amount of 1-2 times of glycine ethyl ester hydrochloride substances at 0.2mL/s, continuing to react under a reflux state, tracking the reaction progress by TLC in the process, naturally cooling to 25 ℃ after the reaction is finished, adding ethyl acetate with the same volume, extracting twice, drying by using enough anhydrous sodium sulfate, distilling under reduced pressure to remove ethyl acetate, and obtaining 1,3, 4-trimethyl-5-ethyl pyrazole, namely ethyl trimethyl pyrazole, and distilling under reduced pressure by an oil pump to obtain a pure product of the ethyl 1,3, 4-trimethyl-5-pyrazole.
Further, 11.9g of glycine ethyl ester hydrochloride was added in the first step.
Further, 11g of sodium nitrite is added in the second step.
Further, 4mL of 5mol/L sulfuric acid was added in the second step.
Further, 2-butanone in an amount of 2 times glycine ethyl ester hydrochloride substance is added dropwise in the third step.
Further, in the third step, the temperature is raised to a boiling reflux state at a speed of 0.5 ℃/s, and the reaction is kept for 22 hours.
Further, dimethyl carbonate was added dropwise in an amount of 1.7 times the amount of glycine ethyl ester hydrochloride substance in the fourth step.
The invention has the following beneficial effects:
Firstly, the synthesis method of the ethyl trimethylpyrazole acid adopts a one-pot method to obtain a product, and takes glycine hydrochloride which is a conventional reagent as a starting material to react with 2-butanone to obtain a first-step product. After the process is finished, the separation treatment step is omitted, dimethyl carbonate is directly added dropwise, and the second reaction is carried out to obtain the final product of 1,3, 4-trimethyl-5-ethyl pyrazolate, namely ethyl trimethylpyrazolate, which is simple to operate.
On one hand, the invention avoids flammable and explosive dangerous processes such as direct diazotization, hydrogenation and the like, and is safe to operate; on the other hand, high-toxicity raw materials such as hydrazine hydrate, methyl hydrazine, ethyl diazoacetate and the like are not used, so that the method is more suitable for a green continuous production process, and accords with the current green safe chemical production concept.
Finally, the invention obtains higher yield of the 1,3, 4-trimethyl-5-pyrazol acid ethyl ester while taking the advantages into consideration, and improves the production benefit.
Drawings
The drawings described herein are included to provide a further understanding and appreciation of the invention. In the drawings:
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum H 1 NMR of ethyl 1,3, 4-trimethyl-5-pyrazolate of the invention in deuterated chloroform environment.
Detailed Description
In order to more clearly illustrate the overall concept of the present invention, the following describes the overall scheme of the present invention in detail by way of examples; in the following description, numerous specific details are set forth in order to provide a more thorough understanding of the present invention; it will be apparent, however, to one skilled in the art that the invention may be practiced without one or more of these details; in other instances, well-known features have not been described in detail in order to avoid obscuring the invention.
Unless otherwise specified, the starting components in the examples below are commercially available, and the laboratory apparatus used is a laboratory conventional laboratory apparatus, and the performance test methods are known in the art. The whole operation space environment is 25 ℃, and the air humidity is 30%. The reduced pressure distillation conditions of the present invention are 110℃and 0.01atm.
The overall reaction route of the invention is as follows:
the preferred embodiment is as follows:
example 1:
the ethyl trimethylpyrazole acid was synthesized using the following steps:
step one: 11.9g of glycine ethyl ester hydrochloride is added into a 50mL round bottom flask, 20mL of deionized water is added, and stirring is carried out for 30min at 25 ℃;
Step two: 11g of sodium nitrite is added, 4mL of sulfuric acid with the concentration of 5mol/L is added dropwise, and the mixture is stirred for 1h at 25 ℃;
Step three: 2-butanone with the amount of 2 times of glycine ethyl ester hydrochloride substances is dropwise added, the temperature is raised to a boiling reflux state at 0.5 ℃ per second, and the reaction is carried out for 22 hours;
Step four: and dropwise adding dimethyl carbonate with the amount of 1.7 times of glycine ethyl ester hydrochloride substance at 0.2mL/s, continuing to react under a reflux state, tracking the reaction progress by TLC in the process, naturally cooling to 25 ℃ after the reaction is finished, adding ethyl acetate with the same volume, extracting twice, drying by using enough anhydrous sodium sulfate, distilling under reduced pressure to remove the ethyl acetate, and obtaining 1,3, 4-trimethyl-5-ethyl pyrazole, namely ethyl trimethyl pyrazole, and distilling under reduced pressure by an oil pump to obtain a pure product of the 1,3, 4-trimethyl-5-ethyl pyrazole.
Examples 2 to 13:
example 2 differs from example 1 only in that 1.39g of glycine ethyl ester hydrochloride are added in step one;
Example 3 differs from example 1 only in that 13.9g of glycine ethyl ester hydrochloride are added in step one;
Example 4 differs from example 1 only in that 0.7g of sodium nitrite is added in step two;
example 5 differs from example 1 only in that 14g of sodium nitrite is added in step two;
example 6 differs from example 1 only in that 1mL of 5mol/L sulfuric acid was added in step two;
example 7 differs from example 1 only in that 5mL of sulfuric acid of 5mol/L is added in step two;
Example 8 differs from example 1 only in that 2-butanone was added dropwise in an amount of 1 time the amount of glycine ethyl ester hydrochloride substance in step three;
example 9 differs from example 1 only in that 2-butanone was added dropwise in an amount of 5 times the amount of glycine ethyl ester hydrochloride substance in step three;
Example 10 differs from example 1 only in that in step three, the heat-preserving reaction is carried out for 8 hours at a temperature of 0.5 ℃/s to a boiling reflux state;
Example 11 differs from example 1 only in that in step three, the heat-preserving reaction is carried out at a temperature of 0.5 ℃/s to a boiling reflux state, and the heat-preserving reaction is carried out for 24 hours;
example 12 differs from example 1 only in that in step four, dimethyl carbonate was added dropwise in an amount of 1 time the amount of glycine ethyl ester hydrochloride substance;
Example 13 differs from example 1 only in that dimethyl carbonate was added dropwise in an amount of 2 times the amount of glycine ethyl ester hydrochloride substance in step four.
Comparative examples 1 to 12:
Comparative example 1 differs from example 1 only in that 0.5g of glycine ethyl ester hydrochloride was added in step one;
Comparative example 2 differs from example 1 only in that 15g of glycine ethyl ester hydrochloride was added in step one;
Comparative example 3 differs from example 1 only in that 0.4g of sodium nitrite was added in step two;
Comparative example 4 differs from example 1 only in that 16g of sodium nitrite was added in step two;
Comparative example 5 differs from example 1 only in that 0.5mL of 5mol/L sulfuric acid was added in step two;
comparative example 6 differs from example 1 only in that 8mL of 5mol/L sulfuric acid was added in step two;
Comparative example 7 differs from example 1 only in that 2-butanone was added dropwise in an amount of 0.5 times the amount of glycine ethyl ester hydrochloride substance in step three;
Comparative example 8 differs from example 1 only in that 2-butanone was added dropwise in an amount of 7 times the amount of glycine ethyl ester hydrochloride substance in step three;
Comparative example 9 differs from example 1 only in that the heat-preserving reaction in step three is that the temperature is raised to a boiling reflux state at 0.5 ℃/s, and the heat-preserving reaction is carried out for 4 hours;
comparative example 10 differs from example 1 only in that the heat-preserving reaction in step three is that the temperature is raised to a boiling reflux state at 0.5 ℃/s, and the heat-preserving reaction is carried out for 30 hours;
Comparative example 11 differs from example 1 only in that dimethyl carbonate was added dropwise in an amount of 0.5 times the amount of glycine ethyl ester hydrochloride substance in step four;
comparative example 12 differs from example 1 only in that dimethyl carbonate was added dropwise in an amount of 3 times the amount of glycine ethyl ester hydrochloride substance in step four.
The pure ethyl 1,3, 4-trimethyl-5-pyrazolate obtained in each example was weighed and the yield calculated, yield = mass obtained/mass obtained, yield results retain the significant figure after the decimal point and are recorded in table 1.
Table 1: yield results of ethyl 1,3, 4-trimethyl-5-pyrazolate obtained in each example:
As can be seen from the data in Table 1, compared with other examples, the yield of the 1,3, 4-trimethyl-5-pyrazolate obtained by the method for synthesizing the trimethylpyrazolate ethyl ester in the embodiment of the invention is highest, namely, the method has higher yield on the basis of combining simplicity and safety in operation and environmental protection and low toxicity.
The foregoing is merely exemplary of the present invention and is not intended to limit the present invention; various modifications and variations of the present invention will be apparent to those skilled in the art; any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are to be included in the scope of the claims of the present invention.
Claims (7)
1. The synthesis method of the ethyl trimethylpyrazole acid is characterized by comprising the following steps of:
Step one: 1.39-13.9 g of glycine ethyl ester hydrochloride is added into a 50mL round bottom flask, 20mL of deionized water is added, and stirring is carried out for 30min at 25 ℃;
Step two: adding 0.7-14 g of sodium nitrite, dropwise adding 1-5 ml of sulfuric acid with the concentration of 5mol/L, and stirring for 1h at 25 ℃;
Step three: 2-butanone with the amount of 1-5 times of glycine ethyl ester hydrochloride substances is dropwise added, and the reaction is carried out for 8-24 hours under the condition of heat preservation;
Step four: and dropwise adding dimethyl carbonate with the amount of 1-2 times of glycine ethyl ester hydrochloride substances at 0.2mL/s, continuing to react under a reflux state, tracking the reaction progress by TLC in the process, naturally cooling to 25 ℃ after the reaction is finished, adding ethyl acetate with the same volume, extracting twice, drying by using enough anhydrous sodium sulfate, distilling under reduced pressure to remove ethyl acetate, and obtaining 1,3, 4-trimethyl-5-ethyl pyrazole, namely ethyl trimethyl pyrazole, and distilling under reduced pressure by an oil pump to obtain a pure product of the ethyl 1,3, 4-trimethyl-5-pyrazole.
2. The method for synthesizing ethyl trimethylpyrazole acid according to claim 1, wherein 11.9g of ethyl glycinate hydrochloride is added in the first step.
3. The method for synthesizing ethyl trimethylpyrazole acid according to claim 1, wherein 11g of sodium nitrite is added in the second step.
4. The method for synthesizing ethyl trimethylpyrazole acetate according to claim 1, wherein 5mol/L sulfuric acid 4mL is added in the second step.
5. The method for synthesizing ethyl trimethylpyrazole acid according to claim 1, wherein 2-butanone is added dropwise in an amount of 2-fold glycine ethyl ester hydrochloride substance in the third step.
6. The method for synthesizing the ethyl trimethylpyrazole acid according to claim 1, wherein the heat preservation reaction in the third step is that the temperature is raised to a boiling reflux state at a speed of 0.5 ℃/s, and the heat preservation reaction is carried out for 22 hours.
7. The method for synthesizing ethyl trimethylpyrazole acid according to claim 1, wherein dimethyl carbonate in an amount of 1.7 times of glycine ethyl ester hydrochloride material is added dropwise in the fourth step.
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| CN114478387A (en) * | 2020-10-28 | 2022-05-13 | 中国科学院大连化学物理研究所 | A kind of synthetic method of 1,3,4-trimethyl-1H-pyrazole-5-carboxylic acid ethyl ester compound |
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| CN102911119B (en) * | 2012-09-30 | 2015-06-17 | 浙江工业大学 | Preparation methods of 3,4-dimethyl pyrazole and 3,4-dimethyl pyrazole phosphate |
| CN112824393A (en) * | 2019-11-21 | 2021-05-21 | 中国科学院大连化学物理研究所 | Preparation method of 3, 4-dimethylpyrazole-5-formate compound |
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| CN114478387A (en) * | 2020-10-28 | 2022-05-13 | 中国科学院大连化学物理研究所 | A kind of synthetic method of 1,3,4-trimethyl-1H-pyrazole-5-carboxylic acid ethyl ester compound |
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