CN112321507A - Preparation method of 3, 4-dimethylpyrazole and phosphate thereof - Google Patents
Preparation method of 3, 4-dimethylpyrazole and phosphate thereof Download PDFInfo
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- CN112321507A CN112321507A CN202010990290.4A CN202010990290A CN112321507A CN 112321507 A CN112321507 A CN 112321507A CN 202010990290 A CN202010990290 A CN 202010990290A CN 112321507 A CN112321507 A CN 112321507A
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- dimethylpyrazole
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- butanone
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- VQTVFIMEENGCJA-UHFFFAOYSA-N 3,4-dimethyl-1H-pyrazole Chemical compound CC=1C=NNC=1C VQTVFIMEENGCJA-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 229910019142 PO4 Inorganic materials 0.000 title abstract description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title abstract description 6
- 239000010452 phosphate Substances 0.000 title abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 37
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 32
- -1 alkenyl ether compound Chemical class 0.000 claims abstract description 21
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims abstract description 21
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 15
- 230000002152 alkylating effect Effects 0.000 claims abstract description 12
- 150000002429 hydrazines Chemical class 0.000 claims abstract description 11
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 7
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- LXKCHCXZBPLTAE-UHFFFAOYSA-N 3,4-dimethyl-1H-pyrazole phosphate Chemical compound OP(O)(O)=O.CC1=CNN=C1C LXKCHCXZBPLTAE-UHFFFAOYSA-N 0.000 claims description 21
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 239000012044 organic layer Substances 0.000 claims description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002168 alkylating agent Substances 0.000 claims description 14
- 229940100198 alkylating agent Drugs 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 8
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 239000008096 xylene Substances 0.000 claims description 6
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 5
- 150000003469 sulfuric acid diesters Chemical class 0.000 claims description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 claims description 4
- 229940008406 diethyl sulfate Drugs 0.000 claims description 4
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 claims description 3
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 3
- AZVCGYPLLBEUNV-UHFFFAOYSA-N lithium;ethanolate Chemical compound [Li+].CC[O-] AZVCGYPLLBEUNV-UHFFFAOYSA-N 0.000 claims description 3
- MXIRPJHGXWFUAE-UHFFFAOYSA-N lithium;propan-1-olate Chemical compound [Li+].CCC[O-] MXIRPJHGXWFUAE-UHFFFAOYSA-N 0.000 claims description 3
- SKTCDJAMAYNROS-UHFFFAOYSA-N methoxycyclopentane Chemical compound COC1CCCC1 SKTCDJAMAYNROS-UHFFFAOYSA-N 0.000 claims description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- AWDMDDKZURRKFG-UHFFFAOYSA-N potassium;propan-1-olate Chemical compound [K+].CCC[O-] AWDMDDKZURRKFG-UHFFFAOYSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- 150000001350 alkyl halides Chemical class 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000002699 waste material Substances 0.000 abstract description 3
- 238000004064 recycling Methods 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- UVEUXDFHYFKUDZ-UHFFFAOYSA-N 4-methoxy-3-methylbut-3-en-2-one Chemical compound COC=C(C)C(C)=O UVEUXDFHYFKUDZ-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- SVICGKIHGOQLKY-UHFFFAOYSA-N 2-methyl-3-oxobutanal;sodium Chemical compound [Na].O=CC(C)C(C)=O SVICGKIHGOQLKY-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 239000000618 nitrogen fertilizer Substances 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 2
- RMOUBSOVHSONPZ-UHFFFAOYSA-N Isopropyl formate Chemical compound CC(C)OC=O RMOUBSOVHSONPZ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- ACWQBUSCFPJUPN-UHFFFAOYSA-N Tiglaldehyde Natural products CC=C(C)C=O ACWQBUSCFPJUPN-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical compound Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- ACWQBUSCFPJUPN-HWKANZROSA-N trans-2-methyl-2-butenal Chemical compound C\C=C(/C)C=O ACWQBUSCFPJUPN-HWKANZROSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a preparation method of 3, 4-dimethylpyrazole and phosphate thereof, which comprises the following steps: s1, in a reaction solvent, adopting an alkaline substance to keep the alkaline condition, reacting 2-butanone and formic ether at the temperature of-10-50 ℃, extracting and separating after the reaction is finished, adding an alkylating reagent to continue the reaction, and preparing a solution of an alkenyl ether compound through post-treatment; s2, reacting the vinyl ether compound prepared in the step S1 with hydrazine hydrate or hydrazine salt at the temperature of-10-60 ℃ after the pH value is adjusted to 2-9, adding the alkaline substance after the reaction is finished, adjusting the pH value to 7-11, and performing post-treatment to obtain the 3, 4-dimethylpyrazole. The preparation method has the remarkable advantages of cheap raw materials, simple and convenient operation, high yield, simple three-waste treatment, high product quality, realization of recycling and reusing of the solvent and the like, and is suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 3, 4-dimethylpyrazole and phosphate thereof.
Background
3, 4-dimethylpyrazole phosphate (DMPP) is a nitrogen fertilizer nitrase inhibitor developed by German BASF, has the characteristics of high efficiency, no toxicity, stability, specificity and the like, is applied to agricultural production in a large scale, is also called as a new generation slow release fertilizer with the best development prospect in the twenty-first century, is also considered as the best nitrogen fertilizer synergist at present, and has wide application prospect.
3, 4-dimethylpyrazole is an important intermediate in the synthesis of 3, 4-dimethylpyrazole phosphate, and many documents are reported on the synthesis thereof. Noyce reports that butanone and isopropyl formate obtain an intermediate under the alkaline action of sodium isopropoxide, and then undergo cyclization reaction with hydrazine hydrate to obtain 3, 4-dimethylpyrazole, and diethyl ether is used as a solvent in the reaction, so that the method is not suitable for large-scale industrial production (J.org.chem.1955,20,1681). U.S. Pat. No. 4, 6022979A discloses that 2-butanone and methyl formate produce 2-methyl-3-oxobutyraldehyde sodium as intermediate under the action of sodium methoxide, and the separated intermediate and hydrazine monohydrate are subjected to cyclization reaction under the catalytic action of sulfuric acid to produce 3, 4-dimethylpyrazole, but the reaction time is as long as 16 hours. The patent with publication number US6229022B discloses direct combination of 2-methyl-2-butenal with hydrazine hydrate, followed by aromatization under the catalysis of concentrated sulfuric acid/sodium iodide to obtain 3, 4-dimethylpyrazole, but this method has extremely high raw material cost and has not achieved commercial production. Patent No. CN102558054A discloses that sodium metal, 2-butanone and ethyl formate are used to produce 2-methyl-3-oxobutyraldehyde sodium, and then the 3, 4-dimethylpyrazole phosphate is prepared through the steps of cyclization, salt formation and the like, and the use of the sodium metal limits that the process can not meet the requirement of large-scale production. Patents CN102311388B and CN102911119B disclose that 2-butanone and paraformaldehyde react under the action of alkaline or protonic acid, and undergo a cyclization reaction with hydrazine hydrate to obtain 3, 4-dimethylpyrazole, which is finally salified to obtain the target product, and paraformaldehyde is a highly toxic and highly carcinogenic substance, and faces serious challenges of occupational health and environmental pollution in the industrial implementation process. Patent No. CN110218188A discloses that enamine compounds are obtained by reacting intermediates obtained after 2-butanone and formic ether react with secondary amine, and 3, 4-dimethylpyrazole is obtained by further reacting with hydrazine hydrate, and 3, 4-dimethylpyrazole phosphate can be further obtained. Patent No. CN110872255A discloses that aldehyde-based alkenyl chloride compound is obtained by reacting 2-butanone, phosphorus oxychloride and N, N-dimethylformamide, and then the aldehyde-based alkenyl chloride compound reacts with hydrazine hydrate to obtain 3, 4-dimethylpyrazole and 3, 4-dimethylpyrazole phosphate.
The synthetic routes and methods disclosed in the above prior art are many, but there are many disadvantages, such as: the cost of raw materials is high, the reaction conditions are harsh, extremely flammable hazardous reagents are involved, the environmental pollution is serious and the like.
Disclosure of Invention
The invention aims to provide a preparation method of 3, 4-dimethylpyrazole and phosphate thereof aiming at the defects in the prior art, and the preparation method has the remarkable advantages of cheap raw materials, simplicity and convenience in operation, high yield, simplicity in three-waste treatment, high product quality, capability of realizing recovery and reuse of a solvent and the like, and is suitable for industrial production.
In order to achieve the purpose, the invention adopts the technical scheme that:
the first aspect of the invention provides a preparation method of 3, 4-dimethylpyrazole, which comprises the following steps:
s1, in a reaction solvent, adopting an alkaline substance to keep the alkaline condition, reacting 2-butanone and formic ether at the temperature of-10-50 ℃, extracting and separating after the reaction is finished, adding an alkylating reagent to continue the reaction, and preparing a solution of an alkenyl ether compound through post-treatment;
s2, reacting the vinyl ether compound prepared in the step S1 with hydrazine hydrate or hydrazine salt at the temperature of-10-60 ℃ after the pH value is adjusted to 2-9, adding the alkaline substance after the reaction is finished to adjust the pH value to 7-11, and performing post-treatment to obtain 3, 4-dimethylpyrazole;
wherein, the substituted ester group R of the formic ester1Alkanyl at C1-C10; the alkylating group R2Is a C1-C10 alkanyl radical.
Preferably, in S1, the reaction solvent is one or more of toluene, 2-methyltetrahydrofuran, nitrobenzene, methyl tert-butyl ether, chlorobenzene, xylene, and methyl cyclopentyl ether.
Preferably, in S1, the basic substance is one or more of sodium methoxide, potassium methoxide, lithium methoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, sodium propoxide, potassium propoxide, lithium propoxide, sodium tert-butoxide, potassium tert-butoxide, and lithium tert-butoxide.
Preferably, in S1, the basic substance is one of sodium methoxide and sodium ethoxide.
Preferably, in S1, the mass ratio of the 2-butanone to the formic ester is 1: 0.9-6.0; the mass ratio of the 2-butanone to the alkaline substance is 1: 0.9-6.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 0.9-5.0.
Preferably, in S1, the mass ratio of the 2-butanone to the formic ester is 1: 1.4-2.6; the mass ratio of the 2-butanone to the alkaline substance is 1: 1.4-2.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 1.2-2.0.
Preferably, the substituted ester group R of the formic ester1Is one of methyl, ethyl, propyl, butyl and isobutyl; the alkylating group R2Is one of methyl and ethyl.
Preferably, in S1, the alkylating agent is one or more of sulfuric acid diesters, halogenated alkanes and sulfonate groups.
Preferably, in S1, the alkylating agent is a sulfuric acid diester.
Preferably, in S1, the alkylating agent is one of dimethyl sulfate and diethyl sulfate.
Preferably, in S1, the specific process of extraction and separation is as follows: controlling the temperature at 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent.
Preferably, in S2, the ratio of the amount of the substance of the enol ether compound to the hydrazine hydrate or the hydrazine salt is 1:0.8 to 3.0.
Preferably, in S2, the ratio of the amount of the substance of the enol ether compound to the hydrazine hydrate or the hydrazine salt is 1:0.9 to 1.3.
Preferably, in S2, the reaction is performed at a temperature of-10 to 60 ℃ after adjusting the pH to 2 to 9, and the substance for adjusting the pH is hydrochloric acid or sulfuric acid.
Preferably, in S2, the post-processing specifically includes: adjusting the pH value of the obtained reaction liquid at 10-60 ℃ to 7-11, adding one or more of toluene, xylene, chlorobenzene and MTBE, standing for layering to obtain an organic layer, and distilling the organic layer under reduced pressure.
The second aspect of the present invention provides a method for preparing 3, 4-dimethylpyrazole phosphate using said 3, 4-dimethylpyrazole as a substrate, comprising the steps of: dissolving the 3, 4-dimethylpyrazole in the reaction solvent, slowly dripping phosphoric acid to adjust the pH value to 1-6, and separating after the reaction is finished to prepare 3, 4-dimethylpyrazole phosphate;
by adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the preparation method of the 3, 4-dimethylpyrazole and the phosphate thereof takes 2-butanone as a raw material, reacts with formic ether under alkaline conditions, then reacts with an alkylating reagent to prepare an enol ether compound, then reacts with hydrazine hydrate or hydrazine salt and is subjected to post-treatment to prepare the 3, 4-dimethylpyrazole, and finally salifying the 3, 4-dimethylpyrazole and phosphoric acid to prepare the 3, 4-dimethylpyrazole phosphate; the preparation method has the remarkable advantages of cheap raw materials, simple and convenient operation, high yield, simple three-waste treatment, high product quality, realization of recycling and reusing of the solvent and the like, and is suitable for industrial production.
Detailed Description
The present invention is further illustrated by the following examples, which are not to be construed as limiting the invention.
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The first aspect of the invention provides a preparation method of 3, 4-dimethylpyrazole, which comprises the following steps:
s1, in a reaction solvent, adopting an alkaline substance to keep the alkaline condition, reacting 2-butanone and formic ether at the temperature of-10-50 ℃, extracting and separating after the reaction is finished, adding an alkylating reagent to continue the reaction, and preparing a solution of an alkenyl ether compound through post-treatment;
s2, reacting the vinyl ether compound prepared in the step S1 with hydrazine hydrate or hydrazine salt at the temperature of-10-60 ℃ after the pH value is adjusted to 2-9, adding the alkaline substance after the reaction is finished to adjust the pH value to 7-11, and performing post-treatment to obtain 3, 4-dimethylpyrazole;
wherein, the substituted ester group R of the formic ester1Alkanyl at C1-C10; the alkylating group R2Is a C1-C10 alkanyl radical.
As a preferred example, in S1, the reaction solvent is one or more selected from toluene, 2-methyltetrahydrofuran, nitrobenzene, methyl tert-butyl ether, chlorobenzene, xylene, and methyl cyclopentyl ether.
As a preferred example, in S1, the basic substance is one or more selected from sodium methoxide, potassium methoxide, lithium methoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, sodium propoxide, potassium propoxide, lithium propoxide, sodium tert-butoxide, potassium tert-butoxide, and lithium tert-butoxide.
As a preferred example, in S1, the basic substance is one of sodium methoxide and sodium ethoxide.
As a preferred example, in S1, the ratio of the amount of the substance of 2-butanone to the substance of formic ester is 1: 0.9-6.0; the mass ratio of the 2-butanone to the alkaline substance is 1: 0.9-6.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 0.9-5.0.
As a preferred example, in S1, the ratio of the amount of the substance of 2-butanone to the substance of formic ester is 1: 1.4-2.6; the mass ratio of the 2-butanone to the alkaline substance is 1: 1.4-2.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 1.2-2.0.
As a preferred embodiment, the substituted ester group R of the formate ester1Is one of methyl, ethyl, propyl, butyl and isobutyl; the alkylating group R2Is one of methyl and ethyl.
As a preferred embodiment, in S1, the alkylating agent is one or more of sulfuric acid diesters, halogenated alkanes and sulfonate groups.
As a preferred embodiment, in S1, the alkylating agent is a sulfuric acid diester.
As a preferred example, in S1, the alkylating agent is one of dimethyl sulfate and diethyl sulfate.
As a preferred embodiment, in S1, the specific process of extraction and separation is as follows: controlling the temperature at 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent.
As a preferred example, in S2, the ratio of the amount of the substance of the enol ether compound and the hydrazine hydrate or the hydrazine salt is 1:0.8 to 3.0.
As a preferred example, in S2, the ratio of the amount of the substance of the enol ether compound and the hydrazine hydrate or the hydrazine salt is 1:0.9 to 1.3.
As a preferred example, in S2, the reaction is carried out at a temperature of-10 to 60 ℃ after adjusting the pH to 2 to 9, and the substance for adjusting the pH is hydrochloric acid or sulfuric acid.
As a preferred embodiment, in S2, the post-processing specifically includes: adjusting the pH value of the obtained reaction liquid at 10-60 ℃ to 7-11, adding one or more of toluene, xylene, chlorobenzene and MTBE, standing for layering to obtain an organic layer, and distilling the organic layer under reduced pressure.
In a second aspect, the present invention provides a method for preparing 3, 4-dimethylpyrazole phosphate using 3, 4-dimethylpyrazole as a substrate, comprising the steps of: dissolving the 3, 4-dimethylpyrazole in the reaction solvent, slowly dripping phosphoric acid to adjust the pH value to 1-6, and separating after the reaction is finished to prepare 3, 4-dimethylpyrazole phosphate;
it is worth noting that the total yield of 3, 4-dimethylpyrazole phosphate obtained is 32-80% calculated on the charge of 2-butanone.
Example 1
Preparation of 3, 4-dimethylpyrazole phosphate:
60g of 2-butanone, 100g of methyl formate and 400g of toluene were put into a reaction flask, and 81g of sodium methoxide solid was added in portions at an internal temperature of-10 to 5 ℃ and then reacted at 10 to 35 ℃ for 4 hours. Controlling the temperature to be 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent. Slowly dropping 189g of dimethyl sulfate into the water phase at the temperature of-10 to 10 ℃ below zero, and reacting for 4 to 6 hours at the temperature of 5 to 35 ℃ after dropping to prepare a solution of 1-methoxy-2-methyl-1-butene-3-one;
adding the prepared 1-methoxy-2-methyl-1-butene-3-one into a three-necked bottle, slowly dropwise adding 58g of 80% hydrazine hydrate solution, slowly dropwise adding hydrochloric acid at the temperature of 15-35 ℃ to adjust the pH value to 5-8, keeping the temperature at 15-45 ℃ for reaction for 2 hours, slowly dropwise adding 20% NaOH aqueous solution to adjust the pH value to 7-10, adding 160g of toluene, standing for layering to obtain an organic layer, and removing the solvent by reduced pressure distillation to obtain a crude product of 3, 4-dimethylpyrazole;
dissolving the prepared 3, 4-dimethylpyrazole in 144g of methanol, adding 85% phosphoric acid at room temperature to adjust the pH value to 3-7, continuing to stir at 15-25 ℃ for reaction for 2 hours, filtering and drying to obtain 103g of 3, 4-dimethylpyrazole phosphate white solid with the total yield of 65%.
Example 2
Preparation of 3, 4-dimethylpyrazole phosphate:
60g of 2-butanone, 100g of methyl formate and 400g of toluene were put into a reaction flask, and 81g of sodium methoxide solid was added in portions at an internal temperature of-10 to 5 ℃ and then reacted at 10 to 35 ℃ for 4 hours. Controlling the temperature to be 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent. Controlling the internal temperature to be-10-10 ℃, slowly dripping 231g of diethyl sulfate into the water phase, and reacting for 4-6 hours at 5-35 ℃ after finishing dripping to prepare a solution of 1-methoxy-2-methyl-1-butene-3-one;
adding the prepared 1-methoxy-2-methyl-1-butene-3-one into a three-necked bottle, slowly dropwise adding 58g of 80% hydrazine hydrate solution, slowly dropwise adding hydrochloric acid at the temperature of 15-35 ℃ to adjust the pH value to 5-8, keeping the temperature at 15-45 ℃ for reaction for 2 hours, slowly dropwise adding 20% NaOH aqueous solution to adjust the pH value to 7-10, adding 160g of toluene, standing for layering to obtain an organic layer, and removing the solvent by reduced pressure distillation to obtain a crude product of 3, 4-dimethylpyrazole;
dissolving the prepared 3, 4-dimethylpyrazole in 144g of methanol, adding 85% phosphoric acid at room temperature to adjust the pH value to 3-7, continuing to stir at 15-25 ℃ for reaction for 2 hours, filtering and drying to obtain 113g of 3, 4-dimethylpyrazole phosphate white solid with the total yield of 71%.
Example 3:
preparation of 3, 4-dimethylpyrazole phosphate:
60g of 2-butanone, 120g of methyl formate and 400g of toluene were charged into a reaction flask, 100g of sodium ethoxide solid was added in portions at an internal temperature of-10 to 5 ℃ and then reacted at 10 to 35 ℃ for 4 hours. Controlling the temperature to be 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent. Controlling the internal temperature to be-10-10 ℃, slowly dripping 236g of methyl iodide into the water phase, reacting for 10-14 hours at 5-35 ℃ after finishing dripping, and directly using the reaction liquid for the next reaction to prepare a solution of 1-methoxy-2-methyl-1-butene-3-one;
adding the prepared 1-methoxy-2-methyl-1-butene-3-one into a three-necked bottle, slowly dropwise adding 58g of 80% hydrazine hydrate solution, slowly dropwise adding hydrochloric acid at the temperature of 15-35 ℃ to adjust the pH value to 5-8, keeping the temperature at 15-45 ℃ for reaction for 2 hours, slowly dropwise adding 20% NaOH aqueous solution to adjust the pH value to 7-10, adding 160g of toluene, standing for layering to obtain an organic layer, and removing the solvent by reduced pressure distillation to obtain a crude product of 3, 4-dimethylpyrazole;
dissolving the prepared 3, 4-dimethylpyrazole in 144g of methanol, adding 85% phosphoric acid at room temperature to adjust the pH value to 3-7, continuing to stir at 15-25 ℃ for reaction for 2 hours, filtering and drying to obtain 62g of 3, 4-dimethylpyrazole phosphate white solid with the total yield of 39%.
Example 4:
preparation of 3, 4-dimethylpyrazole phosphate:
60g of 2-butanone, 100g of methyl formate and 520g of chlorobenzene were added to a reaction flask, 81g of sodium methoxide solid was added in portions at an internal temperature of-10 to 5 ℃ and then reacted at 10 to 35 ℃ for 4 hours. Controlling the temperature to be 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent. Slowly dropping 189g of dimethyl sulfate into the water phase at the temperature of-10 to 10 ℃ below zero, and reacting for 4 to 6 hours at the temperature of 5 to 35 ℃ after dropping to prepare a solution of 1-methoxy-2-methyl-1-butene-3-one;
adding the prepared 1-methoxy-2-methyl-1-butene-3-one into a three-necked bottle, adding 98g of hydrazine hydrochloride solid in batches, controlling the temperature to be 15-35 ℃, slowly dripping hydrochloric acid to adjust the pH value to be 4-6, keeping the temperature at 15-45 ℃, reacting for 2 hours, slowly dripping 20% NaOH aqueous solution to adjust the pH value to be 8-11, adding 240g of chlorobenzene, standing, layering to obtain an organic layer, and removing the solvent by reduced pressure distillation to obtain a crude product of 3, 4-dimethylpyrazole;
dissolving the prepared 3, 4-dimethylpyrazole in 144g of methanol, adding 85% phosphoric acid at room temperature to adjust the pH value to 3-7, continuing to stir at 15-25 ℃ for reaction for 2 hours, filtering and drying to obtain 119g of 3, 4-dimethylpyrazole phosphate white solid with the total yield of 75%.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (16)
1. A preparation method of 3, 4-dimethylpyrazole is characterized by comprising the following steps:
s1, in a reaction solvent, adopting an alkaline substance to keep the alkaline condition, reacting 2-butanone and formic ether at the temperature of-10-50 ℃, extracting and separating after the reaction is finished, adding an alkylating reagent to continue the reaction, and preparing a solution of an alkenyl ether compound through post-treatment;
s2, reacting the vinyl ether compound prepared in the step S1 with hydrazine hydrate or hydrazine salt at the temperature of-10-60 ℃ after the pH value is adjusted to 2-9, adding the alkaline substance after the reaction is finished to adjust the pH value to 7-11, and performing post-treatment to obtain 3, 4-dimethylpyrazole;
wherein, the substituted ester group R of the formic ester1Alkanyl at C1-C10; the alkylating group R2Is a C1-C10 alkanyl radical.
2. The process for preparing 3, 4-dimethylpyrazole according to claim 1, wherein in S1, the reaction solvent is one or more selected from toluene, 2-methyltetrahydrofuran, nitrobenzene, methyl tert-butyl ether, chlorobenzene, xylene, and methylcyclopentyl ether.
3. The method according to claim 1, wherein in S1, the basic substance is one or more selected from sodium methoxide, potassium methoxide, lithium methoxide, sodium ethoxide, potassium ethoxide, lithium ethoxide, sodium propoxide, potassium propoxide, lithium propoxide, sodium t-butoxide, potassium t-butoxide, and lithium t-butoxide.
4. The method according to claim 3, 4-dimethylpyrazole, wherein in S1, the basic substance is one of sodium methoxide and sodium ethoxide.
5. The process for producing 3, 4-dimethylpyrazole according to claim 1, wherein the amount of said substance of 2-butanone and said substance of formic ester is 1:0.9-6.0 in S1; the mass ratio of the 2-butanone to the alkaline substance is 1: 0.9-6.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 0.9-5.0.
6. The process for producing 3, 4-dimethylpyrazole according to claim 5, wherein the amount of said substance of 2-butanone and said substance of formic ester is 1:1.4-2.6 in S1; the mass ratio of the 2-butanone to the alkaline substance is 1: 1.4-2.0; the mass ratio of the 2-butanone to the alkylating agent is 1: 1.2-2.0.
7. The process for preparing 3, 4-dimethylpyrazole according to claim 1, wherein said substituted ester group R of said formic acid ester1Is one of methyl, ethyl, propyl, butyl and isobutyl; the alkylating group R2Is one of methyl and ethyl.
8. The method for preparing 3, 4-dimethylpyrazole according to claim 1, wherein in S1, said alkylating agent is one or more of sulfuric acid diester, haloalkane and sulfonate.
9. The method according to claim 8, wherein the alkylating agent in S1 is a diester sulfate.
10. The method according to claim 9, wherein the alkylating reagent in S1 is one of dimethyl sulfate and diethyl sulfate.
11. The method for preparing 3, 4-dimethylpyrazole according to claim 1, wherein in S1, the specific process of extraction and separation is as follows: controlling the temperature at 0-15 ℃, adding water, stirring, standing for layering, and concentrating the organic layer under reduced pressure to recover the solvent.
12. The process for preparing 3, 4-dimethylpyrazole according to claim 1, wherein the amount of said substance of said enol ether compound and said hydrazine hydrate or hydrazine salt in S2 is 1: 0.8-3.0.
13. The process for preparing 3, 4-dimethylpyrazole according to claim 12, wherein the amount of said substance of said enol ether compound and said hydrazine hydrate or hydrazine salt in S2 is 1: 0.9-1.3.
14. The method for preparing 3, 4-dimethylpyrazole according to claim 1, wherein in S2, the reaction is carried out at a temperature of-10 to 60 ℃ after adjusting the pH to 2 to 9, and the substance for adjusting the pH is hydrochloric acid or sulfuric acid.
15. The method for preparing 3, 4-dimethylpyrazole according to claim 1, wherein in S2, the post-treatment comprises the following steps: adjusting the pH value of the obtained reaction liquid at 10-60 ℃ to 7-11, adding one or more of toluene, xylene, chlorobenzene and MTBE, standing for layering to obtain an organic layer, and distilling the organic layer under reduced pressure.
16. A method for producing 3, 4-dimethylpyrazole phosphate using 3, 4-dimethylpyrazole according to claim 1 as a substrate, comprising the steps of: dissolving the 3, 4-dimethylpyrazole in the reaction solvent, slowly dripping phosphoric acid to adjust the pH value to 1-6, and separating after the reaction is finished to prepare 3, 4-dimethylpyrazole phosphate;
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