CN117777034A - Synthesis method of difluoromethyl triazolinone intermediate with reduced fluoride ion content - Google Patents
Synthesis method of difluoromethyl triazolinone intermediate with reduced fluoride ion content Download PDFInfo
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- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 title claims abstract description 35
- 238000001308 synthesis method Methods 0.000 title claims abstract description 16
- YTMYQMTUVUCXRQ-UHFFFAOYSA-N 1-(difluoromethyl)-4H-triazol-5-one Chemical compound FC(F)N1N=NCC1=O YTMYQMTUVUCXRQ-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 102
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 37
- 239000011737 fluorine Substances 0.000 claims abstract description 37
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 32
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000002994 raw material Substances 0.000 claims abstract description 20
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 18
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 11
- 150000001340 alkali metals Chemical class 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000004327 boric acid Substances 0.000 claims abstract description 10
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 31
- 239000000460 chlorine Substances 0.000 claims description 31
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- -1 salt compounds Chemical class 0.000 claims description 25
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims description 20
- 229910021538 borax Inorganic materials 0.000 claims description 16
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 16
- 230000018044 dehydration Effects 0.000 claims description 15
- 238000006297 dehydration reaction Methods 0.000 claims description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims description 14
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 claims description 12
- JKWMSGQKBLHBQQ-UHFFFAOYSA-N diboron trioxide Chemical compound O=BOB=O JKWMSGQKBLHBQQ-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- XDVOLDOITVSJGL-UHFFFAOYSA-N 3,7-dihydroxy-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound O1B(O)OB2OB(O)OB1O2 XDVOLDOITVSJGL-UHFFFAOYSA-N 0.000 claims description 2
- 235000010338 boric acid Nutrition 0.000 claims description 2
- 125000005619 boric acid group Chemical group 0.000 claims description 2
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- VGTPKLINSHNZRD-UHFFFAOYSA-N oxoborinic acid Chemical compound OB=O VGTPKLINSHNZRD-UHFFFAOYSA-N 0.000 claims description 2
- 239000004328 sodium tetraborate Substances 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 238000010189 synthetic method Methods 0.000 claims 3
- 239000002516 radical scavenger Substances 0.000 claims 2
- 239000002351 wastewater Substances 0.000 abstract description 11
- 239000012295 chemical reaction liquid Substances 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 5
- 239000000047 product Substances 0.000 abstract description 5
- 229910045601 alloy Inorganic materials 0.000 abstract description 4
- 239000000956 alloy Substances 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000000084 colloidal system Substances 0.000 abstract description 2
- 239000011521 glass Substances 0.000 abstract description 2
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 230000002035 prolonged effect Effects 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 238000010438 heat treatment Methods 0.000 description 29
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- 238000005070 sampling Methods 0.000 description 19
- 239000007788 liquid Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 12
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 10
- 229940067157 phenylhydrazine Drugs 0.000 description 10
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 238000004321 preservation Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 239000000575 pesticide Substances 0.000 description 6
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- YQVZREHUWCCHHX-UHFFFAOYSA-N (4-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(Cl)C=C1 YQVZREHUWCCHHX-UHFFFAOYSA-N 0.000 description 5
- 239000005708 Sodium hypochlorite Substances 0.000 description 5
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
- 238000012544 monitoring process Methods 0.000 description 5
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 0.000 description 4
- 239000012452 mother liquor Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 238000009388 chemical precipitation Methods 0.000 description 2
- 238000006115 defluorination reaction Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
- 239000005578 Mesotrione Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000242583 Scyphozoa Species 0.000 description 1
- 229910000676 Si alloy Inorganic materials 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 230000001112 coagulating effect Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000002848 electrochemical method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- KPUREKXXPHOJQT-UHFFFAOYSA-N mesotrione Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)C)=CC=C1C(=O)C1C(=O)CCCC1=O KPUREKXXPHOJQT-UHFFFAOYSA-N 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of compound synthesis, and particularly relates to a synthesis method of a difluoromethyl triazolinone intermediate for reducing fluoride ion content. The method comprises the steps of taking a compound (I) as a raw material, carrying out cyclization reaction to obtain an intermediate (II), oxidizing to obtain an intermediate (III), dehydrating with alkali metal in an aprotic solvent environment at a high temperature to form salt, adding a fluorine removing agent, and obtaining the Intermediate (IV) under certain reaction conditions. The invention uses boric acid and other compounds as defluorinating agent, the consumption is less, the defluorinating effect is better, the use of metal defluorinating agent to produce colloid complex is avoided, the reaction waste water is easier to treat, the product in the waste water is recovered, the product yield is improved, the fluorine ion content in the reaction liquid can be controlled below 50ppm, the fluorine ion content in the reaction waste water can be controlled below 10ppm, and the use of expensive alloy as the inner sleeve of the reaction kettle can be avoided, the service life of the glass lining reaction kettle is prolonged, the replacement frequency is reduced, and the production cost is reduced.
Description
Technical Field
The invention belongs to the field of compound synthesis, and particularly relates to a synthesis method of a difluoromethyl triazolinone intermediate for reducing fluoride ion content.
Background
The fluorine-containing pesticide has the advantages of high selectivity, high adaptability, high added value, low cost, low toxicity, low residue, environmental friendliness and the like, and is a trend of development of modern pesticides. Over 100 of the last decade, newly developed or just patented internationallyAmong chemical pesticides, the fluorine-containing pesticide is approximately half, especially contains CF 3 、CF 2 、OCF 3 、OCH 2 F 2 、OCF 2 CHF 2 、OCH 2 CF 3 、SOCF 3 Pesticides with an equal structure become a hot spot for developing new pesticides.
In the reaction process, a certain amount of fluoride ions are often contained in the reaction system due to the influence of the conditions such as raw materials, solvents, temperature, pressure and the like. When the concentration of the fluoride ions is higher than a certain value, certain corrosion can be caused to equipment, the service life is shortened, the obtained intermediate or product can also have adverse effects on subsequent application, and the fluoride ions in the wastewater can cause great harm to soil, water bodies, animals, plants and the like.
Currently, technologies for removing fluoride ions mainly include an electrochemical method, a chemical precipitation method, an adsorption method, a coagulation precipitation method, an ion exchange method and a membrane filtration method. The various fluorine removal techniques have advantages and disadvantages and are used according to the actual production environment, for example, patent CN106431936a uses a chemical precipitation method to remove fluorine ions generated during the reaction. In the process of synthesizing the fluorine-containing intermediate, a coagulating sedimentation method can be used, aluminum salt is used as a coagulant, and sediment is generated after complex is formed with fluoride ions for defluorination, but the method has the advantages that the aluminum addition amount is more than 10 times of the defluorination amount, the consumption of reagents is large, waste water is gelatinous in the sedimentation process, the separation is difficult, meanwhile, the waste water is difficult to reach the discharge standard, and the waste water cannot be recycled. The patent CN210646415U and the patent CN212167392U use the coating of a high silicon alloy inner sleeve and a hastelloy-C276 to prevent HF from corroding reaction equipment, and the same alloy inner sleeve is high in price and high in maintenance cost.
Disclosure of Invention
Aiming at the problems that hydrogen fluoride generated in the synthesis process corrodes a reaction kettle, an alloy inner sleeve is high in price, the traditional fluorine removal agent is poor in fluorine removal effect, waste water is difficult to treat and the like in the prior art, the invention provides a synthesis method of a difluoromethyl triazolinone intermediate for reducing the content of fluorine ions.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the invention provides a synthesis method of a difluoromethyl triazolinone intermediate for reducing the content of fluoride ions, which comprises the following steps: taking a compound (I) as a raw material, performing cyclization reaction to obtain an intermediate (II), oxidizing to obtain an intermediate (III), dehydrating with alkali metal in an aprotic solvent environment at high temperature to form salt, adding a fluorine removing agent, and obtaining the Intermediate (IV) under certain reaction conditions;
。
further, when the intermediate (III) is the intermediate (IIIa), dehydrating with alkali metal in an aprotic solvent environment to form salt at high temperature, adding a fluorine removing agent, and introducing chlorodifluoromethane to obtain the intermediate (IVa);
the structural formula of the intermediate (IIIa) is as follows:
；
the structural formula of the intermediate (IVa) is as follows:
。
further, when the intermediate (III) is the intermediate (IIIb), dehydrating with alkali metal in an aprotic solvent environment to form salt at high temperature, adding a fluorine removing agent, and introducing chlorodifluoromethane to obtain the intermediate (IVb);
the structural formula of the intermediate (IIIb) is as follows:
；
the structural formula of the intermediate (IVb) is as follows:
。
further, when the intermediate (III) is the intermediate (IIIc), dehydrating the intermediate (IIIc) with alkali metal in an aprotic solvent at a high temperature to form a salt, adding a fluorine removing agent, and introducing chlorodifluoromethane to obtain an intermediate (IVc);
the structural formula of the intermediate (IIIc) is as follows:
；
the structural formula of the intermediate (IVc) is as follows:
。
in the synthesis method provided by the invention, chlorine is introduced into an aprotic solvent from the intermediate (IVa), the intermediate (IVb) is obtained through reaction, a fluorine removing agent is added after the reaction is finished, the temperature is raised for desolventizing, and the intermediate (IVa) is transferred into a reaction kettle into which acetic acid water and the fluorine removing agent are added after the desolventizing is finished.
Further, adding a fluorine removing agent into the mixed solution of the intermediate (IVb) and the acetic acid water, and introducing chlorine to react to obtain an intermediate (IVc).
In the synthesis process of the invention, the alkali metal is carbonate; preferably, the carbonate is potassium carbonate; the aprotic solvent is DMF, DMA or acetonitrile; preferably, the aprotic solvent is DMF.
Further, the fluorine removing agent is boric acid and salt compounds thereof, metaboric acid and salt compounds thereof, tetraboric acid and salt compounds thereof, and diboron trioxide; preferably, the fluorine removing agent is one or more of boric acid, sodium borate and sodium tetraborate.
Further, the molar ratio of the fluorine removing agent to the intermediate is 0.1:100-1:100; preferably, the molar ratio is 0.3:100-0.5:100.
In the synthetic reaction process provided by the invention, the process of generating a certain amount of fluoride ions due to side reaction in a reaction system is as follows:
。
the fluorine ion generated in the preparation process of the mesotrione intermediate and the fluorine ion generated in the post-reaction treatment process can be greatly reduced by adding the fluorine removing agent, and the specific process is as follows:
。
the beneficial effects of the invention are as follows:
(1) The invention uses boric acid and other compounds as defluorinating agent, the consumption is less, the defluorinating effect is better, the use of metal defluorinating agent to generate colloid complex is avoided, the reaction waste water is easier to treat, the product in the waste water is recovered, the product yield is improved, the content of fluorine ions in the reaction liquid can be controlled below 50ppm, and the content of fluorine ions in the reaction waste water can be below 10 ppm;
(2) The synthesis method provided by the invention can avoid using expensive alloy as the inner sleeve of the reaction kettle, prolong the service life of the glass lining reaction kettle, reduce the replacement frequency and reduce the production cost;
Detailed Description
The technical scheme of the invention is further explained and illustrated by specific examples.
In some embodiments, when phenylhydrazine is used as a reaction raw material, condensation reaction is carried out with aqueous solution of acetaldehyde or acetaldehyde, quantitative sodium cyanate and acidic substances are added after the reaction is finished to carry out cyclization reaction to obtain an intermediate (IIa), oxidation is carried out after the cyclization reaction is finished to obtain an intermediate (IIIa), high-temperature dehydration is carried out on the intermediate (IIa) and alkali metal carbonate in an aprotic solvent environment to form salt, a fluorine removing agent is added, and chlorodifluoromethane is introduced to obtain the intermediate (IVa).
In some embodiments, when p-chlorophenylhydrazine hydrochloride is used as a reaction raw material, a one-step neutralization reaction is performed to obtain an intermediate (Ib), the intermediate (IIIb) is synthesized according to the method of claim 2, the intermediate (Ib) is dehydrated to form salt with alkali metal carbonate at a high temperature in an aprotic solvent environment, a fluorine removing agent is added, chlorodifluoromethane is introduced to obtain the intermediate (IVb), the temperature is raised, the negative pressure desolventizing is performed, and the acetic acid water is added after the desolventizing is finished.
In the synthesis method provided by the invention, the conditions for preparing the intermediate (IVb) from the intermediate (IVa) and preparing the intermediate (IVc) from the intermediate (IVb) are carried out according to patent CN 109232450A.
In the synthesis method provided by the invention, the aprotic solvent desolventizing condition is that the vacuum degree is more than or equal to 80KPa, preferably more than or equal to 90KPa; the desolventizing temperature is 85-135 ℃, preferably 120-130 ℃.
In the synthesis method provided by the invention, the distillation of the acetic acid jellyfish solution can be selected from normal pressure distillation and reduced pressure distillation, and the reduced pressure distillation is preferred; the desolventizing temperature is 75-120 ℃, preferably 85-95 ℃; the mass ratio of the fluorine removing agent to the acetic acid aqueous mother solution is 0.05:100-0.5:100, preferably 0.1:100-0.3:100.
Example 1
Adding 80% tertiary butanol aqueous solution and phenylhydrazine into a reaction kettle, replacing with nitrogen at a feed-liquid ratio of 1:6, dropwise adding 38% acetaldehyde aqueous solution, controlling the reaction temperature to 5-10 ℃, keeping the temperature for 30min after the dropwise adding, and detecting in a central control manner. Transferring the materials to a cyclizing oxidation reaction kettle after the reaction is qualified, adding sodium cyanate solid, controlling the reaction temperature to be 5-10 ℃, dropwise adding a certain amount of acetic acid after nitrogen replacement, preserving heat for 1h after the dropwise adding, and performing central control detection. And (3) adding sodium hypochlorite solution with the content of 9% which is 6.5 times of that of phenylhydrazine after the reaction is qualified, controlling the reaction temperature to be 20-30 ℃, finishing the dropwise addition, preserving the heat and reacting for 30min, and performing central control monitoring to obtain a qualified intermediate (IIIa).
Adding a certain amount of DMF and an intermediate (IIIa) into a reaction kettle, stirring and dissolving the mixture, adding a certain amount of potassium carbonate into the mixture at a feed-liquid ratio of 1:5, heating the mixture under negative pressure for reflux dehydration, stopping dehydration after the water content of the reaction kettle is detected to be qualified, transferring the mixture into the reaction kettle into which sodium borate is added, heating the mixture to 140-150 ℃, introducing a certain amount of difluoro-chloromethane, carrying out heat preservation reaction for 30min, cooling the mixture to 85-90 ℃, filtering potassium salt to obtain DMF solution containing the intermediate (IVa), and sampling and detecting the fluorine ion content.
The molar ratio of the raw materials is phenylhydrazine: acetaldehyde: sodium cyanate: acetic acid: potassium carbonate: difluoro chloromethane: sodium borate=1:1:1:1.15:0.8:1.2:0.0035.
The fluoride ion content was 30ppm.
The specific reaction route is as follows:
。
example 2
Adding 80% tertiary butanol aqueous solution and p-chlorophenylhydrazine hydrochloride into a reaction kettle, replacing with nitrogen at a feed liquid ratio of 1:6, dropwise adding 30% sodium hydroxide aqueous solution for neutralization to obtain p-chlorophenylhydrazine, controlling the pH=7.0 of the reaction solution, dropwise adding 38% acetaldehyde aqueous solution, controlling the reaction temperature to 5-10 ℃, keeping the temperature for 30min after the dropwise adding is finished, and performing central control detection. Transferring the materials to a cyclizing oxidation reaction kettle after the reaction is qualified, adding sodium cyanate solid, controlling the reaction temperature to be 5-10 ℃, dropwise adding quantitative acetic acid after nitrogen replacement, preserving heat for 1h after the dropwise adding, and detecting in a central control way. And (3) adding sodium hypochlorite solution with the content of 11% which is 6 times of the mass of the parachlorophenylhydrazine hydrochloride after the reaction is qualified, controlling the reaction temperature to be 20-30 ℃, finishing the dropwise addition, carrying out heat preservation reaction for 30min, and carrying out central control monitoring to obtain a qualified intermediate (IIIb).
Adding a certain amount of DMF and an intermediate (IIIb) into a reaction kettle, stirring and dissolving, adding a certain amount of potassium carbonate, heating to negative pressure for reflux and dehydration, stopping dehydration after the water content in the reaction kettle is detected to be qualified, transferring into the reaction kettle into which sodium borate is added, heating to 140-150 ℃, introducing a certain amount of difluoro chloromethane, carrying out heat preservation reaction for 30min, cooling to 85-90 ℃, filtering potassium salt, obtaining DMF solution containing the intermediate (IVb), and sampling and detecting the fluorine ion content.
The molar ratio of the raw materials is p-chlorophenylhydrazine hydrochloride: acetaldehyde: sodium cyanate: acetic acid: potassium carbonate: difluoro chloromethane: sodium borate=1:1:1:1.15:0.8:1.2:0.0035.
The fluoride ion content was 28ppm.
。
Example 3
Adding a certain amount of DMF and an intermediate (IIIc) into a reaction kettle, stirring and dissolving, adding a certain amount of potassium carbonate, heating to negative pressure for reflux and dehydration, stopping dehydration after the water content in the reaction kettle is detected to be qualified, transferring into the reaction kettle into which sodium borate is added, heating to 140-150 ℃, introducing a certain amount of difluoro chloromethane, carrying out heat preservation reaction for 30min, cooling to 85-90 ℃, filtering potassium salt, obtaining DMF solution containing the intermediate (IVc), and sampling and detecting the fluorine ion content.
The raw material molar ratio is an intermediate (IIIc): potassium carbonate: difluoro chloromethane: sodium borate=1:0.8:1.2: 0.0035.
the fluoride ion content was 40ppm.
。
Example 4
Adding DMF solution containing intermediate (IVa) into a reaction kettle, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 125 ℃ to stop desolventizing, adding acidic DMF, cooling to 20 ℃ to sample and detect the fluorine ion content, starting chlorine introduction, stopping chlorine introduction when the central control is not turned to be less than 1%, adding quantitative sodium borate after the reaction is finished, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 127 ℃ to stop desolventizing, recycling the acidic DMF, transferring the rest materials to the reaction kettle to which the acetic acid water and the defluorinating agent are added, and sampling to detect the fluorine ion content.
The molar ratio of the raw materials is intermediate (IVa): chlorine: sodium borate=1:1.2:0.0035.
The fluorine ion content is 35ppm before chlorine introduction and 78ppm after chlorine introduction.
。
Example 5
Adding acetic acid water into a reaction kettle, adding the intermediate (IVb) obtained in the embodiment 4, sampling and detecting the content of fluoride ions, adding quantitative sodium borate, heating to 80 ℃, starting to introduce chlorine, stopping introducing chlorine when the central control is not turned to be less than 1%, cooling and crystallizing, and sampling and detecting the content of fluoride ions in the reaction liquid. And centrifuging, washing and drying the crystallization liquid to obtain an intermediate (IVc).
The raw material molar ratio is an intermediate (IIIb): chlorine: sodium borate=1:1.5:0.0035.
The fluorine ion content is 78ppm before chlorine introduction and 42ppm after chlorine introduction.
。
Example 6
Adding 80% tertiary butanol aqueous solution and phenylhydrazine into a reaction kettle, replacing with nitrogen, dropwise adding 40% acetaldehyde aqueous solution, controlling the reaction temperature to be 5-10 ℃, keeping the temperature for 30min after the dropwise adding, and detecting in a central control manner. Transferring the materials to a cyclizing oxidation reaction kettle after the reaction is qualified, adding sodium cyanate solid, controlling the reaction temperature to be 5-10 ℃, dropwise adding a certain amount of acetic acid after nitrogen replacement, preserving heat for 1h after the dropwise adding, and performing central control detection. And (3) adding sodium hypochlorite solution with the content of 11% accounting for 6 times of the mass of phenylhydrazine after the reaction is qualified, controlling the reaction temperature to be 20-30 ℃, and performing central control monitoring after the feeding is finished and the reaction is performed for 30min to obtain a qualified intermediate (IIIa).
Adding a certain amount of DMF and an intermediate (IIIa) into a reaction kettle, stirring and dissolving, adding a certain amount of potassium carbonate, heating to negative pressure for reflux and dehydration, stopping dehydration after the moisture of the reaction kettle is detected to be qualified, transferring into the reaction kettle into which diboron trioxide is added, heating to 140-150 ℃, introducing a certain amount of difluoro chloromethane, carrying out heat preservation reaction for 30min, cooling to 85-90 ℃, filtering potassium salt, obtaining DMF solution containing the intermediate (IVa), and sampling and detecting the fluoride ion content.
The molar ratio of the raw materials is phenylhydrazine: acetaldehyde: sodium cyanate: acetic acid: potassium carbonate: difluoro chloromethane: diboron trioxide=1:1:1:1.15:0.8:1.2:0.0035.
The fluoride ion content was 55ppm.
Example 7
Adding DMF solution containing intermediate (IVa) into a reaction kettle, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 125 ℃, stopping desolventizing, adding acidic DMF, cooling to 20 ℃, sampling to detect the fluorine ion content, starting chlorine introduction, stopping chlorine introduction when the central control is not turned to be less than 1%, adding quantitative boric acid after the reaction is finished, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 127 ℃, stopping desolventizing, transferring to the reaction kettle to which the acetic acid and the defluorinating agent are added, sampling to detect the fluorine ion content.
The molar ratio of the raw materials is intermediate (IVa): chlorine: boric acid=1:1.2:0.0035.
The fluorine ion content is 35ppm before chlorine introduction and 80ppm after chlorine introduction.
Example 8
Adding the crystallization liquid centrifugal mother liquor obtained in the example 5 into a reaction kettle, adding quantitative sodium borate, heating to negative pressure, distilling to recover acetic acid water, controlling the vacuum degree to 90KPa, stopping distilling at 90 ℃, reducing the temperature to 30 ℃, adding liquid alkali into the residue of the distillation kettle to neutralize the pH value to neutral, sampling, detecting the fluorine ion content, filtering, performing environmental protection treatment on the filtrate, and recovering the filtered material for crystallization.
The mass ratio of the raw materials is that the crystallization liquid is centrifugated mother liquor: sodium borate=1:0.0015.
The fluoride ion content was 10ppm.
Example 9
Adding the crystallization liquid centrifugal mother liquor obtained in the example 5 into a reaction kettle, adding quantitative boric acid, heating to negative pressure, distilling to recover acetic acid water, controlling the vacuum degree to 90KPa, stopping distilling at 90 ℃, reducing the temperature to 30 ℃, adding liquid alkali into the residue of the distillation kettle to neutralize the pH value to neutral, sampling, detecting the fluorine ion content, filtering, performing environment-friendly treatment on the filtrate, and recovering the filtrate for crystallization.
The mass ratio of the raw materials is that the crystallization liquid is centrifugated mother liquor: boric acid=1:0.0015.
The fluoride ion content was 25ppm.
Comparative example 1
Adding 80% tertiary butanol aqueous solution and phenylhydrazine into a reaction kettle, replacing the materials with nitrogen according to a feed liquid ratio of 1:6, dropwise adding 38-40% acetaldehyde aqueous solution, controlling the reaction temperature to be 5-10 ℃, preserving the heat for 30min after the dropwise adding, and detecting in a central control manner. Transferring the materials to a cyclizing oxidation reaction kettle after the reaction is qualified, adding sodium cyanate solid, controlling the reaction temperature to be 5-10 ℃, dropwise adding a certain amount of acetic acid after nitrogen replacement, preserving heat for 1h after the dropwise adding, and performing central control detection. And (3) adding sodium hypochlorite solution with the content of 11% accounting for 6 times of the mass of phenylhydrazine after the reaction is qualified, controlling the reaction temperature to be 20-30 ℃, and performing central control monitoring after the feeding is finished and the reaction is performed for 30min to obtain a qualified intermediate (IIIa).
Adding a certain amount of DMF and an intermediate (IIIa) into a reaction kettle, stirring and dissolving, adding a certain amount of potassium carbonate, heating to negative pressure for reflux and dehydration, stopping dehydration after the moisture of the reaction kettle is detected to be qualified, transferring into the reaction kettle into which aluminum sulfate is added, heating to 140-150 ℃, introducing a certain amount of difluoro chloromethane, carrying out heat preservation reaction for 30min, cooling to 85-90 ℃, filtering potassium salt, obtaining DMF solution containing the intermediate (IVa), and sampling and detecting the fluorine ion content.
The molar ratio of the raw materials is phenylhydrazine: acetaldehyde: sodium cyanate: acetic acid: potassium carbonate: difluoro chloromethane: aluminum sulfate=1:1:1:1.15:0.8:1.2:0.0035.
The fluoride ion content was 203ppm.
Comparative example 2
Adding 80% tertiary butanol aqueous solution and p-chlorophenylhydrazine hydrochloride into a reaction kettle, replacing with nitrogen at a feed-liquid ratio of 1:6, dropwise adding a quantitative sodium hydroxide aqueous solution to neutralize to obtain p-chlorophenylhydrazine, controlling the reaction temperature to be 5-10 ℃, keeping the temperature for 30min after dropwise adding, and performing central control detection. Transferring the materials to a cyclizing oxidation reaction kettle after the reaction is qualified, adding sodium cyanate solid, controlling the reaction temperature to be 5-10 ℃, dropwise adding a certain amount of acetic acid after nitrogen replacement, preserving heat for 1h after the dropwise adding, and performing central control detection. And (3) adding sodium hypochlorite solution with the content of 11% accounting for 6 times of the mass of the parachlorophenylhydrazine hydrochloride after the reaction is qualified, controlling the reaction temperature to be 20-30 ℃, and performing central control monitoring after the feeding is finished and the heat preservation reaction is performed for 30min to obtain a qualified intermediate (IIIb).
Adding a certain amount of DMF and an intermediate (IIIb) into a reaction kettle, stirring and dissolving, adding a certain amount of potassium carbonate, heating to negative pressure for reflux dehydration, stopping dehydration after the moisture of the reaction kettle is detected to be qualified, transferring into the reaction kettle into which aluminum sulfate is added, heating to 140-150 ℃, introducing a certain amount of difluoro chloromethane, carrying out heat preservation reaction for 30min, cooling to 85-90 ℃, filtering potassium salt, obtaining DMF solution containing the intermediate (IVb), and sampling and detecting the fluorine ion content.
The molar ratio of the raw materials is p-chlorophenylhydrazine hydrochloride: acetaldehyde: sodium cyanate: acetic acid: potassium carbonate: difluoro chloromethane: aluminum sulfate=1:1:1:1.15:0.8:1.2:0.0035.
The fluoride ion content was 152ppm.
Comparative example 3
Adding DMF solution containing intermediate (IVa) into a reaction kettle, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 125 ℃ to stop desolventizing, adding acidic DMF, cooling to 20 ℃, sampling to detect the content of fluorine ions, starting chlorine introduction, stopping chlorine introduction when the central control is not turned to be less than 1%, adding quantitative aluminum sulfate after the reaction is finished, heating to negative pressure desolventizing, controlling the vacuum degree to 90KPa, heating to 127 ℃ to stop desolventizing, recycling the acidic DMF, transferring the rest materials to the reaction kettle to which the acetic acid water and the defluorinating agent are added, sampling to detect the content of fluorine ions.
The molar ratio of the raw materials is intermediate (IVa): chlorine: aluminum sulfate=1:1.2:0.0035.
The fluorine ion content is 35ppm before chlorine introduction and 149ppm after chlorine introduction.
Comparative example 4
Adding acetic acid water into a reaction kettle, adding the intermediate (IVb) obtained in the comparative example 3, sampling and detecting the content of fluoride ions at a feed-liquid ratio of 1:6, adding quantitative aluminum sulfate, heating to 80 ℃, starting to introduce chlorine, stopping introducing chlorine when the central control is not turned to be less than 1%, cooling and crystallizing, and sampling and detecting the content of fluoride ions in the reaction liquid. And centrifuging, washing and drying the crystallization liquid to obtain an intermediate (IVc).
The raw material molar ratio is an intermediate (IIIb): chlorine: aluminum sulfate=1:1.5:0.0015.
The fluorine ion content is 149ppm before chlorine introduction and 542ppm after chlorine introduction.
Comparative example 5 (without defluorinating agent)
Adding acetic acid water into a reaction kettle, adding the intermediate (IVb) obtained in the comparative example 3, sampling and detecting the content of fluoride ions in the mixture at a feed-liquid ratio of 1:6, heating to 80 ℃, starting to introduce chlorine gas, stopping introducing the chlorine gas when the central control is not turned to be less than 1%, cooling and crystallizing, and sampling and detecting the content of the fluoride ions in the reaction liquid. And centrifuging, washing and drying the crystallization liquid to obtain an intermediate (IVc).
The raw material molar ratio is an intermediate (IIIb): chlorine: aluminum sulfate=1:1.5:0.0015.
The fluorine ion content is 149ppm before chlorine introduction and 1042ppm after chlorine introduction.
Effect examples
The production costs of example 5 and comparative examples 4 and 5 were counted and the specific results are shown in table 1.
TABLE 1
。
Claims (10)
1. A method for synthesizing a difluoromethyl triazolinone intermediate with reduced fluoride ion content, which is characterized by comprising the following steps: taking a compound (I) as a raw material, performing cyclization reaction to obtain an intermediate (II), oxidizing to obtain an intermediate (III), dehydrating with alkali metal in an aprotic solvent environment at high temperature to form salt, adding a fluorine removing agent, and obtaining the Intermediate (IV) under certain reaction conditions;
。
2. the synthesis method according to claim 1, wherein when the intermediate (iii) is the intermediate (iiia), the intermediate (iva) is obtained by high-temperature dehydration with alkali metal in an aprotic solvent environment to form a salt, adding a fluorine removing agent, and introducing chlorodifluoromethane;
the structural formula of the intermediate (IIIa) is as follows:
；
the structural formula of the intermediate (IVa) is as follows:
。
3. the synthesis method according to claim 1, wherein when the intermediate (iii) is the intermediate (ibj), the intermediate (ibj) is obtained by high-temperature dehydration with an alkali metal in an aprotic solvent environment to form a salt, adding a fluorine removing agent, and introducing chlorodifluoromethane;
the structural formula of the intermediate (IIIb) is as follows:
；
the structural formula of the intermediate (IVb) is as follows:
。
4. the synthesis method according to claim 1, wherein when the intermediate (iii) is the intermediate (iiic), the intermediate (iiic) is dehydrated with alkali metal in an aprotic solvent to form a salt at a high temperature, a fluorine removing agent is added, and chlorodifluoromethane is introduced to obtain the intermediate (ivc);
the structural formula of the intermediate (IIIc) is as follows:
；
the structural formula of the intermediate (IVc) is as follows:
。
5. a synthesis method according to claim 2 or 3, wherein the intermediate (iva) is chlorinated in an aprotic solvent, the intermediate (ivb) is obtained by reaction, the fluorine removing agent is added after the reaction is finished, the temperature is raised to remove the solvent, and the reaction is carried out in a reaction kettle to which the acetic acid water and the fluorine removing agent are added after the removal of the solvent is finished.
6. The synthesis method according to claim 3 or 4, wherein a fluorine removing agent is added to the mixed solution of the intermediate (IVb) and acetic acid water, and chlorine is introduced to react to obtain the intermediate (IVc).
7. The synthetic method of any one of claims 1-4 wherein the alkali metal is carbonate; preferably, the carbonate is potassium carbonate.
8. The synthetic method according to any one of claims 1 to 5, wherein the aprotic solvent is DMF, DMA, acetonitrile; preferably, the aprotic solvent is DMF.
9. The method according to any one of claims 1 to 8, wherein the fluorine scavenger is boric acid and its salt compounds, metaboric acid and its salt compounds, tetraboric acid and its salt compounds, diboron trioxide; preferably, the fluorine removing agent is one or more of boric acid, sodium borate and sodium tetraborate.
10. The synthetic method according to any one of claims 1 to 9, wherein the molar ratio of the fluorine scavenger to the intermediate is 0.1:100 to 1:100; preferably, the molar ratio is 0.3:100-0.5:100.
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