CN104326891A - Preparation method of 3-trifluoromethylpyrazole intermediate - Google Patents

Preparation method of 3-trifluoromethylpyrazole intermediate Download PDF

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CN104326891A
CN104326891A CN201410618142.4A CN201410618142A CN104326891A CN 104326891 A CN104326891 A CN 104326891A CN 201410618142 A CN201410618142 A CN 201410618142A CN 104326891 A CN104326891 A CN 104326891A
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preparation
trifluoromethyl pyrazol
trifluoroacetic acid
reaction
acylating reagent
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樊小彬
徐晓明
郭胜强
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LIANHUA TECHNOLOGY (YANCHENG) Co Ltd
LIANHE CHEMICAL TECHNOLOGY (SHANGHAI) Co Ltd
Lianhe Chemical Technology Co Ltd
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LIANHUA TECHNOLOGY (YANCHENG) Co Ltd
LIANHE CHEMICAL TECHNOLOGY (SHANGHAI) Co Ltd
Lianhe Chemical Technology Co Ltd
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Priority to CN201410618142.4A priority Critical patent/CN104326891A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C07C45/47—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation using phosgene
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/78—Separation; Purification; Stabilisation; Use of additives
    • C07C45/86—Use of additives, e.g. for stabilisation
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/582—Recycling of unreacted starting or intermediate materials

Abstract

The invention discloses a preparation method of a 3-trifluoromethylpyrazole intermediate. The preparation method is characterized by comprising the following step: carrying out reaction on trifluoroacetic acid, an acylation reagent and vinyl alkyl ether disclosed as Formula 1 in an organic solvent in the presence of an acid-binding agent to obtain 4-alkoxy-1,1,1-trifluoro-3-butenyl-2-one, wherein the acylation reagent is one or more of phosgene, diphosgene and triphosgene, and R is C1-C6 alkyl group. The preparation method has the advantages of fewer reaction steps, mild reaction conditions, environment friendliness, simple after-treatment steps, high reaction yield, high product purity and low production cost, and is suitable for industrial production.

Description

The preparation method of 3-trifluoromethyl pyrazol intermediate
Technical field
The present invention is specifically related to the preparation method of 3-trifluoromethyl pyrazol intermediate.
Background technology
4-oxyethyl group-1,1,1-tri-fluoro-3-butene-2-one is the important intermediate of preparation 3-trifluoromethyl pyrazol, and 3-trifluoromethyl pyrazol can be used for synthesizing antiviral, microbiotic, sterilant, weedicide etc., can be used for the intermediate synthesizing respiratory system class medicine, such as cough medicine simultaneously.Its synthetic method at home and abroad more report.
In document, the synthetic method of 4-oxyethyl group-1,1,1-tri-fluoro-3-butene-2-one mainly contains following several:
(1) with trifluoroacetic anhydride and ethyl vinyl ether for raw material is obtained by reacting in the presence of a base in a solvent, alkali comprises (the Journal of Fluorine Chemitry such as pyridine, DMAP (4-DMAP), methyl tertiary butyl ether, triethylamine, 2011,132,850-857).Generate a part trifluoroacetic acid after using trifluoroacetic acid anhydride reactant and have neither part nor lot in reaction, raw material availability is low.
(2) obtain for raw material carries out addition reaction in the presence of a base in a solvent with trifluoroacetyl chloride and ethyl vinyl ether, alkali comprises (US5708175, its patent families is EP0744400) such as pyridine, quinoline, triethylamine, xylidine, Diethyl Aniline, DMAPs; Eliminate after addition hydrogenchloride can adopt heating or add alkali neutralization (CN102471202A, CN102112428A and CN102341361A).Trifluoroacetic acid need be used to prepare trifluoroacetyl chloride, and simultaneous reactions aftertreatment is more complicated, and environmental pollution is serious, is not suitable for suitability for industrialized production.
(3) trifluoroacetyl chloride and ethyl vinyl ether also can carry out addition reaction in solvent-free, remove hydrogenchloride (CN1832911A) by heating or low pressure.Trifluoroacetic acid need be used to prepare trifluoroacetyl chloride, and simultaneous reactions aftertreatment is complicated, and environmental pollution is serious, is not suitable for suitability for industrialized production.
(4), under the salt of trifluoroacetic acid exists, ethyl vinyl ether and trifluoroacetyl chloride or trifluoroacetic anhydride at room temperature react.Solvent comprises methylene dichloride, hexane etc., also can without solvent, the preferred trifluoroacetic acid picoline (CN1330622C) of salt.Trifluoroacetic anhydride raw material availability is low, and production cost is high, and trifluoroacetic acid need be used to prepare trifluoroacetyl chloride, and environmental pollution is serious, is not suitable for suitability for industrialized production.
Summary of the invention
Technical problem to be solved by this invention is to overcome existing 4-oxyethyl group-1,1, preparation method's reactions steps of 1-tri-fluoro-3-butene-2-one is many, severe reaction conditions, environmental pollution is serious, post-processing step is loaded down with trivial details, reaction yield is low, production cost is high, be unfavorable for the defects such as suitability for industrialized production and provide the preparation method of 3-trifluoromethyl pyrazol intermediate, and preparation method's reactions steps of the present invention is few, reaction conditions is gentle, environmental friendliness, post-processing step are easy, reaction yield is high, product purity is high, production cost is low, be suitable for suitability for industrialized production.
The invention provides the preparation method of 3-trifluoromethyl pyrazol intermediate, it comprises the following steps: in organic solvent, under acid binding agent existent condition, trifluoroacetic acid, acylating reagent and vinyl alkyl ethers are as shown in Equation 1 reacted, obtain 4-alkoxyl group-1 as shown in Equation 2,1,1-tri-fluoro-3-butene-2-one; Described acylating reagent is one or more in phosgene, trichloromethylchloroformate and triphosgene;
Wherein, R is C 1~ C 6alkyl (such as methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-or the tertiary butyl).
In the present invention, described organic solvent can be the conventional organic solvent of such reaction in this area, particularly preferably aromatic hydrocarbon solvent and/or halogenated hydrocarbon solvent in the present invention.The preferred toluene of described aromatic hydrocarbon solvent and/or dimethylbenzene, further preferred toluene; The preferred chlorinated hydrocarbon solvent of described halogenated hydrocarbon solvent, the preferred methylene dichloride of described chlorinated hydrocarbon solvent.
In the present invention, described organic solvent after the completion of reaction can recycling.
In the present invention, the preferred 1:3 ~ 1:20 of mass ratio of described trifluoroacetic acid and described organic solvent, further preferred 1:5 ~ 1:15.
In the present invention, described acid binding agent can be the conventional acid binding agent of such reaction in this area, particularly preferably organic bases in the present invention; The preferred pyridine of described organic bases and/or triethylamine, further preferred pyridine.
In the present invention, the preferred 1:2 ~ 1:5 of mol ratio of described trifluoroacetic acid and described acid binding agent, further preferred 1:2 ~ 1:3.
In the present invention, described acid binding agent after the completion of reaction can recycling.
In the present invention, the preferred 1.5:1 ~ 1:1.5 of mol ratio of described trifluoroacetic acid and described vinyl alkyl ethers as shown in Equation 1, further preferred 1:1 ~ 1:1.4.
In the present invention, the preferred 1:1 ~ 1:3 of mol ratio of described trifluoroacetic acid and described acylating reagent, further preferred 1:1.1 ~ 1:1.5.
In the present invention, the temperature of described reaction preferably-5 DEG C ~ 50 DEG C, preferably 5 DEG C ~ 10 DEG C further.
In the present invention, the process of described reaction can adopt the routine monitoring method (such as TLC or HPLC) in this area to monitor, for reaction end when disappearing with vinyl alkyl ethers as shown in Equation 1, preferably 1 hour ~ 10 hours reaction times, preferably 2 hours ~ 6 hours further.
In the present invention, described reaction preferably includes device for absorbing tail gas, described device for absorbing tail gas can be conventional in this area can the device for absorbing tail gas of absorbing carbon dioxide and hydrogenchloride.The aqueous solution of particularly preferably mineral alkali in the present invention, the preferred potassium hydroxide of described mineral alkali and/or sodium hydroxide; The mass percentage concentration of the aqueous solution of described mineral alkali preferably 5% ~ 30%, described mass percentage concentration refers to that the quality of mineral alkali accounts for the per-cent of inorganic base aqueous solution total mass.
In the present invention, described reaction preferably includes following post-processing step: after reaction terminates, add water, and organic phase alkali cleaning concentrates the fluoro-3-butene-2-one of 4-alkoxyl group-1,1,1-tri-as shown in Equation 2 after obtaining purifying.The GC purity of the fluoro-3-butene-2-one of 4-alkoxyl group-1,1,1-tri-as shown in Equation 2 after purifying is greater than 98%.The fluoro-3-butene-2-one of 4-alkoxyl group-1,1,1-tri-is as shown in Equation 2 the intermediate of 3-trifluoromethyl pyrazol, and Cis-trans structures does not affect next step building-up reactions (reaction of preparation 3-trifluoromethyl pyrazol).
In the present invention, in the post-processing step of described reaction, the mode of dropping when adding water, is preferably adopted to carry out, the temperature of described dropping preferably 0 DEG C ~ 10 DEG C.
In the present invention, in the post-processing step of described reaction, the preferred mineral alkali of described alkali; One or more in the preferred sodium bicarbonate of described mineral alkali, saleratus, sodium carbonate and salt of wormwood, further preferably sodium bicarbonate and/or saleratus.Preferred 5:1 ~ the 1:5 of mol ratio of described trifluoroacetic acid and described mineral alkali.Described mineral alkali can use with the form of its aqueous solution.When described mineral alkali uses with the form of its aqueous solution, the mass concentration of the aqueous solution of described mineral alkali preferably 1% ~ 30%, described mass concentration refers to that the quality of described mineral alkali accounts for the per-cent of the aqueous solution total mass of described mineral alkali.
In the present invention, the preparation method of described 3-trifluoromethyl pyrazol intermediate preferably includes following steps: in the solution that vinyl alkyl ethers as shown in Equation 1, acid binding agent and organic solvent are formed, drip trifluoroacetic acid, then pass into acylating reagent to react, obtain 4-alkoxyl group-1 as shown in Equation 2,1,1-tri-fluoro-3-butene-2-one; Described acylating reagent is one or more in phosgene, trichloromethylchloroformate and triphosgene.
In the preferred step of preparation method of described 3-trifluoromethyl pyrazol intermediate, the temperature of described dropping trifluoroacetic acid preferably 0 ~ 20 DEG C.
In the preferred step of preparation method of described 3-trifluoromethyl pyrazol intermediate, the described temperature passing into acylating reagent preferably-10 DEG C ~ 35 DEG C, preferred-2 ~ 10 DEG C further.
In the preferred step of preparation method of described 3-trifluoromethyl pyrazol intermediate, the described preferred 0.1mol/h ~ 1mol/h of the speed passing into acylating reagent, further preferred 0.3mol/h ~ 0.6mol/h.
In the preferred step of preparation method of described 3-trifluoromethyl pyrazol intermediate, pass into preferably 3 hours ~ 5 hours reaction times after acylating reagent.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can arbitrary combination, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material are all commercially.
Positive progressive effect of the present invention is:
1, preparation method of the present invention adopts one kettle way to react, and reactions steps is few.
2, the organic solvent adopted in the present invention and acid binding agent can recyclings; Acylating reagent (phosgene, trichloromethylchloroformate and triphosgene) is cheap and easy to get, and reaction terminate after add water and just can remove excessive acylating reagent, production cost is reduced greatly, and environmental friendliness.
3, reaction conditions of the present invention is gentle, post-processing step is easy, reaction yield is high (being not less than 93%), product purity high (GC purity is not less than 98%), production cost are low, be suitable for suitability for industrialized production.
Embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
Embodiment 1
Ethyl vinyl ether 26.56g (0.368mol), 450g toluene, triethylamine 53.25g (0.526mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 31.5g (0.316mol) and about need 1 hour; Logical closing slowly is warming up to 0 DEG C of insulation 5 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 43.3g after precipitation; GC (A) purity 99%, yield is 97%, 100% is cis-structure.
Embodiment 2
Ethyl vinyl ether 20.87g (0.289mol), 150g dimethylbenzene, pyridine 52.03g (0.658mol) is added in the 500mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 34.36g (0.347mol) and about need 1 hour; Logical closing slowly is warming up to 10 DEG C, is incubated 3 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, it is 5%NaHCO that organic layer adds 100g mass percent 3the aqueous solution stirs insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the xylene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 43.8g after precipitation; GC (A) purity 99%, yield is 98%, 100% is cis-structure.
Embodiment 3
Ethyl vinyl ether 19g (0.263mol), 600g methylene dichloride, pyridine 83.25g (1.052mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 54.65g (0.526mol) and about need 1 hour; Logical closing slowly is warming up to 20 DEG C of insulations 3 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the dichloromethane solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 43.5g after precipitation; GC (A) purity 99%, yield is 97.5%, 100% is cis-structure.
Embodiment 4
Ethyl vinyl ether 12.5g (0.174mol), 90g toluene, pyridine 41.6g (0.526mol) is added in the 500mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 10 DEG C, pass into phosgene 26g (0.263mol) and about need 1 hour; Logical closing slowly is warming up to 30 DEG C of insulations 3 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 29g after precipitation; GC (A) purity 99%, yield 98% (being that main raw material calculates with ethyl vinyl ether), 100% is cis-structure.
Embodiment 5
Ethyl vinyl ether 26.56g (0.368mol), 450g toluene, triethylamine 40g (0.395mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 31.5g (0.316mol) and about need 1 hour; Logical closing slowly is warming up to 15 DEG C of insulations 5 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs, and is incubated 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 44.2g after precipitation; GC (A) purity 99%, yield is 99%, 100% is cis-structure.
Embodiment 6
In with thermometer, prolong, in the 1000mL four-hole boiling flask of device for absorbing tail gas, room temperature adds water 130g, sodium bicarbonate 3.5g (0.038mol), 50% hydrazine hydrate 32.5g (0.324mol), stir ice bath and lower the temperature 0 DEG C, drip 4-oxyethyl group-1, 1, toluene (400g) solution of 1-tri-fluoro-3-butene-2-one 50g (0.294mol), control temperature is lower than 5 DEG C, within 1 hour, be added dropwise to complete, 0 DEG C is incubated 5 hours, detect 4-oxyethyl group-1, 1, 1-tri-fluoro-3-butene-2-one complete reaction, leave standstill 0 DEG C of layering, toluene layer adds 10% hydrochloric acid 150g0 DEG C of washing, stratification, it is 97% that toluene layer detects 3-trifluoromethyl pyrazol mass content calculating reaction yield, air distillation, obtain 3-trifluoromethyl pyrazol 39.6g (0.288mol) GC (A) purity 99%, yield 98%.
Embodiment 7
Methoxy ethylene 20.59g (0.368mol), 450g toluene, triethylamine 50g (0.494mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 31.5g (0.316mol) and about need 1 hour; Logical closing slowly is warming up to 15 DEG C of insulations 4 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 120g mass percent is 5% 3the aqueous solution stirs, and is incubated 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-methoxyl group-1,1,1-tri-, obtains product 40.52g after precipitation; GC (A) purity 99%, yield is 99%, 100% is cis-structure.
Embodiment 8
Vinyl hexyl ether 47.22g (0.368mol), 350g toluene, triethylamine 40g (0.395mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, pass into phosgene 40.5g (0.409mol) and about need 1 hour; Logical closing slowly is warming up to 15 DEG C of insulations 4 hours, drips water 100g, and 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs, and is incubated 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-hexyloxy-1,1,1-tri-, obtains product 58.93g after precipitation; GC (A) purity 99%, yield is 99%, 100% is cis-structure.
Comparative example 1
Ethyl vinyl ether 26.56g (0.368mol), 450g toluene, triethylamine 40g (0.395mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 0 DEG C, drip 31.5g (0.158mol) trichloromethylchloroformate and about need 1 hour; Drip to finish and be slowly warming up to 15 DEG C of insulations 5 hours, lower the temperature 10 DEG C and drip water 100g, 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, it is 5%NaHCO that organic layer adds 100g mass percent 3stir insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leave standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 37.8g after precipitation; GC (A) purity 95%, yield is 90%, 100% is cis-structure.
Comparative example 2
Ethyl vinyl ether 26.56g (0.368mol), 350g toluene, triethylamine 40g (0.395mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, lower the temperature 10 DEG C, drip triphosgene 31.5g (0.105mol) toluene 100g solution and about need 1 hour; Drip to finish and be slowly warming up to 15 DEG C of insulations 5 hours, lower the temperature 10 DEG C and drip water 100g, 10 DEG C are stirred insulation 0.5 hour, and leave standstill, layering, organic layer adds the NaHCO that 100g mass percent is 5% 3the aqueous solution stirs insulation 0.5 hour (described mass percent refers to that the quality of sodium bicarbonate accounts for the per-cent of sodium bicarbonate aqueous solution total mass), leaves standstill, layering; Organic layer obtains the toluene solution of the fluoro-3-butene-2-one of 4-oxyethyl group-1,1,1-tri-, obtains product 35.7g after precipitation; GC (A) purity 95%, yield is 85%, 100% is cis-structure.
Comparative example 3
Ethyl vinyl ether 26.56g (0.368mol), 450g toluene, triethylamine 40g (0.395mol), pyridine 20.8g (0.263mol) is added in the 1000mL four-hole boiling flask of thermometer, prolong, device for absorbing tail gas, ice bath lowers the temperature 0 DEG C, drip trifluoroacetic acid 30g (0.263mol) control temperature lower than 20 DEG C, within 0.5 hour, be added dropwise to complete, 15 DEG C are incubated 5 hours, and middle control detects and do not find target product.

Claims (11)

  1. The preparation method of 1.3-trifluoromethyl pyrazol intermediate, it is characterized in that comprising the following steps: in organic solvent, under acid binding agent existent condition, trifluoroacetic acid, acylating reagent and vinyl alkyl ethers are as shown in Equation 1 reacted, obtain 4-alkoxyl group-1 as shown in Equation 2,1,1-tri-fluoro-3-butene-2-one; Described acylating reagent is one or more in phosgene, trichloromethylchloroformate and triphosgene;
    Wherein, R is C 1~ C 6alkyl.
  2. 2. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 1, is characterized in that: described R is methyl, ethyl, propyl group, sec.-propyl, butyl, isobutyl-or the tertiary butyl.
  3. 3. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 1, is characterized in that: described organic solvent is aromatic hydrocarbon solvent and/or halogenated hydrocarbon solvent;
    And/or the mass ratio of described trifluoroacetic acid and described organic solvent is 1:3 ~ 1:20;
    And/or described acid binding agent is organic bases;
    And/or the mol ratio of described trifluoroacetic acid and described acid binding agent is 1:2 ~ 1:5;
    And/or the mol ratio of described trifluoroacetic acid and described vinyl alkyl ethers is as shown in Equation 1 1.5:1 ~ 1:1.5;
    And/or the mol ratio of described trifluoroacetic acid and described acylating reagent is 1:1 ~ 1:3;
    And/or the temperature of described reaction is-5 DEG C ~ 50 DEG C.
  4. 4. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 3, is characterized in that: described aromatic hydrocarbon solvent is toluene and/or dimethylbenzene; Described halogenated hydrocarbon solvent is chlorinated hydrocarbon solvent;
    And/or the mass ratio of described trifluoroacetic acid and described organic solvent is 1:5 ~ 1:15;
    And/or described organic bases is pyridine and/or triethylamine;
    And/or the mol ratio of described trifluoroacetic acid and described acid binding agent is 1:2 ~ 1:3;
    And/or the mol ratio of described trifluoroacetic acid and described vinyl alkyl ethers is as shown in Equation 1 1:1 ~ 1:1.4;
    And/or the mol ratio of described trifluoroacetic acid and described acylating reagent is 1:1.1 ~ 1:1.5;
    And/or the temperature of described reaction is 5 DEG C ~ 10 DEG C.
  5. 5. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 1, it is characterized in that: described reaction comprises following post-processing step: after reaction terminates, add water, organic phase alkali cleaning, the concentrated 4-alkoxyl group-1 as shown in Equation 2 obtaining GC purity and be greater than 98%, 1,1-tri-fluoro-3-butene-2-one.
  6. 6. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 5, is characterized in that: in the post-processing step of described reaction, adopts the mode dripped to carry out when adding water; The temperature of described dropping is 0 DEG C ~ 10 DEG C;
    And/or,
    In the post-processing step of described reaction, described alkali is mineral alkali.
  7. 7. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 6, is characterized in that: in the post-processing step of described reaction, and described mineral alkali is one or more in sodium bicarbonate, saleratus, sodium carbonate and salt of wormwood; Described mineral alkali can use with the form of its aqueous solution, when described mineral alkali uses with the form of its aqueous solution, the mass concentration of the aqueous solution of described mineral alkali is 1% ~ 30%, and described mass concentration refers to that the quality of described mineral alkali accounts for the per-cent of the aqueous solution total mass of described mineral alkali;
    And/or,
    The mol ratio of described trifluoroacetic acid and described mineral alkali is 5:1 ~ 1:5.
  8. 8. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 1, it is characterized in that: the preparation method of described 3-trifluoromethyl pyrazol intermediate specifically comprises the following steps: in the solution that vinyl alkyl ethers as shown in Equation 1, acid binding agent and organic solvent are formed, drip trifluoroacetic acid, then pass into acylating reagent to react, obtain 4-alkoxyl group-1 as shown in Equation 2,1,1-tri-fluoro-3-butene-2-one; Described acylating reagent is one or more in phosgene, trichloromethylchloroformate and triphosgene.
  9. 9. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 8, it is characterized in that: in preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, the temperature of described dropping trifluoroacetic acid is 0 ~ 20 DEG C;
    And/or,
    In preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, the described temperature passing into acylating reagent is-10 DEG C ~ 35 DEG C;
    And/or,
    In preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, the described speed passing into acylating reagent is 0.1mol/h ~ 1mol/h.
  10. 10. the preparation method of 3-trifluoromethyl pyrazol intermediate as claimed in claim 9, is characterized in that: in preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, the described temperature passing into acylating reagent is-2 ~ 10 DEG C;
    And/or,
    In preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, the described speed passing into acylating reagent is 0.3mol/h ~ 0.6mol/h.
  11. The preparation method of 11. 3-trifluoromethyl pyrazol intermediates as claimed in claim 8, is characterized in that: in preparation method's concrete steps of described 3-trifluoromethyl pyrazol intermediate, and after passing into acylating reagent, the reaction times is 3 hours ~ 5 hours.
CN201410618142.4A 2014-11-05 2014-11-05 Preparation method of 3-trifluoromethylpyrazole intermediate Pending CN104326891A (en)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105237376A (en) * 2015-11-20 2016-01-13 江苏瑞邦农药厂有限公司 Synthesizing method for 4-oxethyl-1,1,1-trifluoro-butene-2-ketone
WO2019224677A1 (en) 2018-05-21 2019-11-28 Pi Industries Ltd. Method for preparing substituted heterocyclic compounds
CN110776405A (en) * 2019-09-30 2020-02-11 安徽金禾实业股份有限公司 Synthetic method of flonicamid intermediate
CN111072463A (en) * 2019-12-03 2020-04-28 辽宁凯莱英医药化学有限公司 Continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one
WO2021108999A1 (en) * 2019-12-03 2021-06-10 辽宁凯莱英医药化学有限公司 Method for continuous synthesis of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one
CN115108897A (en) * 2021-03-23 2022-09-27 帕潘纳(北京)科技有限公司 Preparation method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one and derivatives thereof

Citations (1)

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CN104072347A (en) * 2014-06-30 2014-10-01 湖南海利化工股份有限公司 Preparation method for 4- alkoxy-1,1,1- trifluoro-3- butane-2-ketone

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CN104072347A (en) * 2014-06-30 2014-10-01 湖南海利化工股份有限公司 Preparation method for 4- alkoxy-1,1,1- trifluoro-3- butane-2-ketone

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105237376A (en) * 2015-11-20 2016-01-13 江苏瑞邦农药厂有限公司 Synthesizing method for 4-oxethyl-1,1,1-trifluoro-butene-2-ketone
WO2019224677A1 (en) 2018-05-21 2019-11-28 Pi Industries Ltd. Method for preparing substituted heterocyclic compounds
CN110776405A (en) * 2019-09-30 2020-02-11 安徽金禾实业股份有限公司 Synthetic method of flonicamid intermediate
CN111072463A (en) * 2019-12-03 2020-04-28 辽宁凯莱英医药化学有限公司 Continuous synthesis method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one
WO2021108999A1 (en) * 2019-12-03 2021-06-10 辽宁凯莱英医药化学有限公司 Method for continuous synthesis of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one
CN115108897A (en) * 2021-03-23 2022-09-27 帕潘纳(北京)科技有限公司 Preparation method of 4-ethoxy-1, 1, 1-trifluoro-3-butene-2-one and derivatives thereof

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