CN117430492B - Preparation method of difluoro acetic acid - Google Patents
Preparation method of difluoro acetic acid Download PDFInfo
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- CN117430492B CN117430492B CN202311752929.5A CN202311752929A CN117430492B CN 117430492 B CN117430492 B CN 117430492B CN 202311752929 A CN202311752929 A CN 202311752929A CN 117430492 B CN117430492 B CN 117430492B
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- PBWZKZYHONABLN-UHFFFAOYSA-N difluoroacetic acid Chemical compound OC(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-N 0.000 title claims abstract description 62
- 238000002360 preparation method Methods 0.000 title claims abstract description 49
- 238000006243 chemical reaction Methods 0.000 claims abstract description 75
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 59
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 59
- 238000005342 ion exchange Methods 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 51
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims abstract description 42
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 42
- 239000011734 sodium Substances 0.000 claims abstract description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 38
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims abstract description 34
- 230000008569 process Effects 0.000 claims abstract description 32
- KLBOFRLEHJAXIU-UHFFFAOYSA-N tributylazanium;chloride Chemical compound Cl.CCCCN(CCCC)CCCC KLBOFRLEHJAXIU-UHFFFAOYSA-N 0.000 claims abstract description 32
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 claims abstract description 31
- DQFXLCKTFSDWHB-UHFFFAOYSA-N 2,2-difluoroacetonitrile Chemical compound FC(F)C#N DQFXLCKTFSDWHB-UHFFFAOYSA-N 0.000 claims abstract description 20
- 230000020477 pH reduction Effects 0.000 claims abstract description 18
- 239000002904 solvent Substances 0.000 claims abstract description 17
- -1 difluoro-carbene Chemical class 0.000 claims abstract description 16
- 238000007344 nucleophilic reaction Methods 0.000 claims abstract description 14
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 6
- RZSJYVBYLBNFGQ-UHFFFAOYSA-N difluoromethane hydrochloride Chemical compound FCF.Cl RZSJYVBYLBNFGQ-UHFFFAOYSA-N 0.000 claims description 31
- 239000000706 filtrate Substances 0.000 claims description 28
- 239000007789 gas Substances 0.000 claims description 27
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 claims description 27
- 239000007788 liquid Substances 0.000 claims description 25
- 238000003756 stirring Methods 0.000 claims description 23
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 22
- 239000003513 alkali Substances 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- 230000035484 reaction time Effects 0.000 claims description 19
- 238000006460 hydrolysis reaction Methods 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 16
- 230000007062 hydrolysis Effects 0.000 claims description 16
- 238000011049 filling Methods 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 15
- 238000004821 distillation Methods 0.000 claims description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 8
- 238000010791 quenching Methods 0.000 claims description 8
- 230000000171 quenching effect Effects 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 238000005349 anion exchange Methods 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 238000007086 side reaction Methods 0.000 abstract description 5
- 230000003647 oxidation Effects 0.000 abstract description 4
- 238000007254 oxidation reaction Methods 0.000 abstract description 4
- 239000007858 starting material Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 description 102
- 230000002572 peristaltic effect Effects 0.000 description 22
- 239000000463 material Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000001514 detection method Methods 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 239000012071 phase Substances 0.000 description 11
- 238000005086 pumping Methods 0.000 description 11
- 230000004584 weight gain Effects 0.000 description 11
- 235000019786 weight gain Nutrition 0.000 description 11
- 239000000047 product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 4
- LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical class OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 125000000218 acetic acid group Chemical class C(C)(=O)* 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 description 1
- PBWZKZYHONABLN-UHFFFAOYSA-M difluoroacetate Chemical compound [O-]C(=O)C(F)F PBWZKZYHONABLN-UHFFFAOYSA-M 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical class [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Chemical class OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910044991 metal oxide Chemical class 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229910001463 metal phosphate Inorganic materials 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/08—Preparation of carboxylic acids or their salts, halides or anhydrides from nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of difluoroacetic acid, belonging to the field of organic synthesis. The sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is prepared in a dipolar solvent such as acetone, difluoro-chloromethane (R22) is used as a starting material, an alkaline environment is provided by the ion exchange system, and the difluoro-carbene is produced by catalyzing R22. The ion exchange system promotes the sodium cyanide and tri-n-butyl ammonium chloride to generate anion exchange, promotes the cyanide and difluoro carbene to generate nucleophilic reaction to obtain difluoro acetonitrile, and obtains difluoro acetic acid through rapid hydrolytic oxidation, acidification and rectification. The process yield is above 62%, and the purity is more than 99%. Compared with the existing process for preparing the difluoroacetic acid, the cyanide source in the reaction process is derived from a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system, so that the reaction is promoted; and the method is carried out in an anhydrous system, so that the occurrence of side reactions is reduced.
Description
Technical Field
The application relates to the field of organic synthesis, in particular to a preparation method of difluoro acetic acid.
Background
Difluoro acetic acid is a fluorine-containing derivative of acetic acid, is used as a fine intermediate, is mainly used for synthesizing medicines, pesticides and dyes containing fluorine, and can also be used as a raw material for a glass coating process: is a catalyst for esterification reaction and condensation reaction, a protective agent for hydroxyl and amino, and is used for synthesizing sugar and polypeptide: is a good solvent for a plurality of organic compounds, is also a good solvent for organic reaction, and has good market prospect.
In the prior art, there are various technological methods for preparing difluoroacetic acid, for example, chinese patent publication No. CN103429565A reports that difluoroacetonitrile and derivatives thereof are prepared from difluorochloromethane (R22) and sodium cyanide as raw materials by a base catalytic reaction in an aqueous system. The reaction is carried out under an aqueous system, and the generated difluoro carbene is quickly hydrolyzed, so that the yield is not high.
The Chinese patent publication No. CN103201245A reports that, by taking tetrafluoroethylene as a raw material, difluoroacetate is generated under the action of any organic solvent halogenated aliphatic compound, ether, alcohol, glycol, ketone, ester and amide, and alkali metal, alkaline earth metal bicarbonate, hydroxide or metal oxide, metal phosphate or hydrogen phosphate to obtain difluoroacetic acid. Because the amount of the tetrafluoroethylene converted into the salt is constant, the yield of the path difluoro acetic acid is lower, the reaction time is longer, and the reaction temperature is higher.
The Chinese patent report with publication No. CN113636926A reports that dialkyl amine, first organic solvent and 10-40% liquid alkali with volume concentration are added into a dry reactor, dichloroacetyl chloride is dripped into the reactor, the organic phase is decompressed, desolventized and concentrated to obtain dichloroacetyl dialkyl amine, potassium fluoride, second organic solvent and dichloroacetyl dialkyl amine are added into another reactor, the molar ratio is 3:5:1, so as to obtain difluoroacetyl dialkyl amine, the equal mass of difluoroacetyl dialkyl amine is mixed with 10-30% liquid alkali, the mixture is refluxed for 4-10h, hydrochloric acid is added into the bottom solution of the reactor after distillation to adjust PH=1, and difluoroacetic acid is obtained by distillation again. The preparation process of the alkylamine is complex and has high temperature; three wastes solids can be generated.
In summary, the existing preparation method of difluoroacetic acid has the technical problems of long reaction time, low product yield, complex reaction system and high requirements on process equipment.
Disclosure of Invention
The method aims at solving the technical problems of long reaction time, low product yield, complex reaction system and high requirements on process equipment in the existing preparation method of the difluoroacetic acid. The technical scheme that this application adopted is: provided is a method for preparing difluoroacetic acid, comprising the steps of:
(1) Filling hydrogen chloride gas into a container filled with tri-n-butylamine for reaction, and adding tri-n-butyl ammonium chloride which is a reaction product into a dipolar solvent containing sodium cyanide to form a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system;
(2) Filling difluoro chloromethane into a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system, heating and stirring to enable the difluoro chloromethane to generate difluoro carbene in a catalysis mode under an alkaline environment provided by the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system, and enabling the difluoro carbene to generate nucleophilic reaction with cyanide in the ion exchange system to generate difluoro acetonitrile;
(3) Cooling, adding liquid alkali for hydrolysis, adding hydrogen peroxide for quenching, and then filtering, rinsing, acidifying and distilling at normal pressure to obtain the difluoro acetic acid.
Preferably, the molar ratio of tri-n-butylamine to difluoromethane is 1.0-1.4:1.
Preferably, the molar ratio of sodium cyanide to difluoromethane is 0.8-1.2:1.
Preferably, in the step (1), the hydrogen chloride charging process and the reaction process with tri-n-butylamine are performed at room temperature.
Preferably, in the step (1), the tri-n-butyl ammonium chloride is added dropwise, the dropwise adding rate is 1.0mL/min, and the system temperature is controlled to be below 25 ℃.
Preferably, in the step (1), the dipolar solvent is any one of acetone, acetonitrile or butanone.
Preferably, in the step (2), the temperature of heating and stirring is 30-50 ℃, and the reaction time is 3.0-5.0h.
Preferably, in step (3), hydrolysis means: cooling the temperature to room temperature after the step (2) is finished; adding liquid alkali at a rate of 1.0-2.0mL/min, hydrolyzing for 2.0h at room temperature, wherein the liquid alkali is sodium hydroxide solution, and the molar ratio of the liquid alkali to the difluoro chloromethane is 2:1.
Preferably, in the step (3), quenching means that hydrogen peroxide solution is added at a rate of 1.0-2.0mL/min after the hydrolysis reaction is finished, and quenching is carried out for 2.0h at room temperature, wherein the molar ratio of the hydrogen peroxide solution to the difluoromethane is 2:1.
Preferably, in the step (3), after the quenching reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid.
The beneficial effects of the invention are as follows:
the invention provides a method for preparing difluoro acetic acid by nucleophilic reaction of difluoro chloromethane (R22) and a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system. Preparing a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system in a dipolar solvent such as acetone, taking difluoro-chloromethane as a starting material, providing an alkaline environment by the ion exchange system, and catalyzing R22 to generate difluoro carbene. The ion exchange system promotes the sodium cyanide and tri-n-butyl ammonium chloride to generate anion exchange, promotes the cyanide and difluoro carbene to generate nucleophilic reaction to obtain difluoro acetonitrile, and obtains difluoro acetic acid through rapid hydrolytic oxidation, acidification and rectification. The process yield is above 62%, and the purity is more than 99%. Compared with the prior process for preparing the difluoroacetic acid, the method has the advantages that:
1. reducing the side reaction of hydrocyanic acid self-polymerization; the reaction can realize higher yield only in the proportion of equimolar equivalent; the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system promotes the anion exchange of sodium cyanide, and can improve the solubility of cyanide sources in a dipolar solvent, thereby improving the possibility of participation of cyanide in nucleophilic attack, being beneficial to forward reaction and improving the defect of insoluble solid sodium cyanide. The solid-liquid opposite strain is changed into a homogeneous reaction, which is favorable for nucleophilic attack, improves the bonding efficiency of difluoro carbene and cyanogen, and finally improves the reaction efficiency and shortens the reaction time;
2. the reaction system is simple, the process for preparing the difluoroacetonitrile is carried out under the anhydrous condition, the competition of side reactions is avoided, the reaction selectivity is improved, and the reaction has better selectivity compared with the reaction in which sodium cyanide is directly used;
3. the reaction condition is mild, the reaction is carried out at normal temperature and normal pressure, and no special requirement is required for equipment; the reactant tri-n-butylamine can be recycled, the recycling step is simple, and the utilization rate is improved;
4. compared with the synthesis process using tetrafluoroethylene as raw material, the method has the advantages of high atomic utilization rate, high product yield and low cost.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following will make a brief description of the drawings used in the embodiments or the description of the prior art.
FIG. 1 is a gas chromatogram of difluoroacetic acid in example 1;
fig. 2 is a mass spectrum of a substance having a peak time of 9.421min in the gas chromatogram shown in fig. 1.
Detailed Description
In order to make the technical problems, technical schemes and beneficial effects to be solved by the present application more clear, the present application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the present application.
Example 1
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.24g of tri-n-butylamine (purity 99%,0.140mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.26g of hydrogen chloride gas (purity 100%,0.117mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
The reaction equation is as follows:
50.05g of acetone, 6.36g of sodium cyanide solid (purity 90%,0.117mol, molar ratio to difluoromethane 1:1) were added successively to a 250ml autoclave equipped with a magnet, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
The reaction equation is as follows:
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.117mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording weight gain of the reactor by 10.10g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
The reaction equation is as follows:
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.20g of a liquid alkaline solution (purity 32%,0.234mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.48g of hydrogen peroxide solution (purity: 30%,0.234mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
The reaction equation is as follows:
after the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.39g, the gas phase detection purity is 99.37%, and the calculated yield is 65.51%.
The reaction equation is as follows:
example 2
The difference between the implementation method and the example 1 is that in the step (1), the molar ratio of tri-n-butylamine to difluoro-chloromethane added into the four-neck flask is 1:1, and the molar ratio of difluoro-chloromethane to the ion exchange system is changed to 1:3 due to the reduction of the adding amount of tri-n-butylamine in the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system, the adding ratio of the rest materials is unchanged, and the adding amount of the materials is calculated according to the proportion.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
into a 250ml four-necked flask equipped with a magnet, 22.37g of tri-n-butylamine (purity: 99%, molar ratio of 0.119mol to difluoromethane: 1:1) was charged, and 4.35g of hydrogen chloride gas (purity: 100%, molar ratio of 0.119mol to difluoromethane: 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.16g of acetone, 6.51g of sodium cyanide solid (purity 90%,0.119mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.119mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3) into the reactor, recording the weight gain of the reactor by 10.33g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.87g of a liquid alkali solution (purity 32%,0.239mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 27.09g of hydrogen peroxide solution (purity: 30%,0.239mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, distilling and collecting fractions at 120-140 ℃ under normal pressure to obtain difluoroacetic acid, wherein the quality is 7.44g, the gas phase detection purity is 99.03%, and the calculated yield is 64.26%.
Example 3
The difference between the implementation method and the example 1 is that in the step (1), the molar ratio of tri-n-butylamine to difluoromethane added into the four-neck flask is 1.4:1, and the molar ratio of the difluoromethane to the ion exchange system is changed to 1:3.4 as the adding amount of tri-n-butylamine in the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is increased, the adding ratio of the rest materials is unchanged, and the adding amount of the materials is calculated according to the proportion.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
to a 250ml four-necked flask equipped with a magnet, 31.07g of tri-n-butylamine (purity: 99%, molar ratio of 0.166mol to difluoromethane: 1.4:1) was charged, and 4.32g of hydrogen chloride gas (purity: 100%, molar ratio of 0.118mol to difluoromethane: 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.28g of acetone, 6.46g of sodium cyanide solid (purity 90%,0.118mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.118mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.4) into the reactor, recording the weight gain of the reactor by 10.25g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.63g of a liquid alkali solution (purity 32%,0.237mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.88g of hydrogen peroxide solution (purity: 30%,0.237mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain difluoroacetic acid, wherein the quality is 7.49g, the gas phase detection purity is 99.15%, and the calculated yield is 65.27%.
As is clear from examples 1 to 3, in the range of 1:1.0 to 1.4 in terms of the molar ratio of tri-n-butylamine to difluoromethane, the product purity and yield were maximized when the molar ratio of tri-n-butylamine to difluoromethane was 1.2:1, and therefore, the molar ratio of tri-n-butylamine to difluoromethane was most preferably 1.2:1.
Example 4
The difference between this embodiment and example 1 is that acetonitrile as a solvent is added to a 250ml autoclave containing magnetons in step (1), the ratio of the materials is not changed, and the amount of the materials added is calculated in proportion.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.92g of tri-n-butylamine (purity 99%,0.144mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.37g of hydrogen chloride gas (purity 100%,0.120mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
50.18g of acetonitrile and 6.52g of sodium cyanide solid (purity 90%,0.120mol, molar ratio to difluoromethane 1:1) were successively added to a 250ml autoclave equipped with a magnet, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.120mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording the weight gain of the reactor by 10.36g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.95g of a liquid alkali solution (purity 32%,0.240mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 27.16g of hydrogen peroxide solution (purity: 30%,0.240mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.53g, the gas phase detection purity is 99.23%, and the calculated yield is 64.98%.
Example 5
The difference between the method and example 1 is that in the step (1), butanone as a solvent was added to a 250mL autoclave containing magnetons, and the addition rate of the liquid alkali and hydrogen peroxide was changed to 2.0mL/min, the material addition ratio was unchanged, and the amount of the added material was calculated in proportion.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.55g of tri-n-butylamine (purity 99%,0.142mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.31g of hydrogen chloride gas (purity 100%,0.118mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.31g of butanone, 6.44g of sodium cyanide solid (purity 90%,0.118mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.118mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording the weight gain of the reactor by 10.23g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.55g of a liquid alkali solution (purity 32%,0.236mol, molar ratio to difluoromethane: 2:1) was added at a rate of 2.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.80g of hydrogen peroxide solution (purity: 30%,0.236mol, molar ratio to difluoromethane: 2:1) was added at a rate of 2.0mL/min by a peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain difluoroacetic acid, wherein the quality is 7.46g, the gas phase detection purity is 99.11%, and the calculated yield is 65.13%.
As is clear from examples 1, 4 and 5, acetone is most preferable as the solvent of the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system because the purity and yield of the product are maximized when acetone is used as the solvent.
Example 6
The difference between the method and example 1 is that in the step (1), the molar ratio of the sodium cyanide solid to the difluoro-chloromethane added into the 250ml autoclave with magneton is changed to 0.8:1, and the molar ratio of the difluoro-chloromethane to the ion exchange system is changed to 1:3, the adding ratio of the rest materials is unchanged, and the adding amount of the materials is calculated according to the proportion because the adding amount of sodium cyanide in the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is reduced.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.71g of tri-n-butylamine (purity 99%,0.143mol, molar ratio to difluoromethane chloride: 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.33g of hydrogen chloride gas (purity 100%,0.119mol, molar ratio to difluoromethane chloride: 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.10g of acetone, 5.18g of sodium cyanide solid (purity 90%,0.095mol, molar ratio to difluoromethane 0.8:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.119mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3) into the reactor, recording the weight gain of the reactor by 10.28g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.72g of a liquid alkali solution (purity 32%,0.238mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.96g of hydrogen peroxide solution (purity: 30%,0.238mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by a peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.20g, the gas phase detection purity is 99.15%, and the calculated yield is 62.51%.
Example 7
The difference between the method and the example 1 is that in the step (1), the molar ratio of the sodium cyanide solid and the difluoro-chloromethane added into the 250ml autoclave with magnetons is changed to be 1.2:1, and the molar ratio of the difluoro-chloromethane and the ion exchange system is changed to be 1:3.4 because the adding amount of sodium cyanide in the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is increased, the adding ratio of the rest materials is unchanged, and the adding amount of the materials is calculated according to the proportion.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.22g of tri-n-butylamine (purity 99%,0.140mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.25g of hydrogen chloride gas (purity 100%,0.117mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
50.09g of acetone, 7.63g of sodium cyanide solid (purity 90%,0.140mol, molar ratio to difluoromethane 1.2:1) were added successively to a 250ml autoclave equipped with a magnet, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.117mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.4) into the reactor, recording the weight gain of the reactor to 10.09g, heating to 40 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.17g of a liquid alkali solution (purity 32%,0.233mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.46g of hydrogen peroxide solution (purity: 30%,0.233mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.39g, the gas phase detection purity is 99.41%, and the calculated yield is 65.58%.
As is evident from examples 1, 6 and 7, when the molar ratio of sodium cyanide to difluoromethane is in the range of 0.8 to 1.2:1, the product purity and yield are maximized when the molar ratio of sodium cyanide to difluoromethane is 1.2:1, and therefore, the molar ratio of sodium cyanide to difluoromethane is most preferably 1.2:1.
Example 8
The material adding proportion of the implementation method and the embodiment 1 is unchanged, and the stirring temperature of the nucleophilic reaction is changed to 30 ℃.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.42g of tri-n-butylamine (purity 99%,0.141mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.29g of hydrogen chloride gas (purity 100%,0.118mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.60g of acetone, 6.40g of sodium cyanide solid (purity 90%,0.118mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.118mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording the weight gain of the reactor by 10.17g, heating to 30 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.40g of a liquid alkali solution (purity 32%,0.235mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.67g of hydrogen peroxide solution (purity: 30%,0.235mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, distilling and collecting fractions at 120-140 ℃ under normal pressure to obtain difluoroacetic acid, wherein the quality is 7.37g, the gas phase detection purity is 99.16%, and the calculated yield is 64.67%.
Example 9
The material adding proportion of the implementation method and the embodiment 1 is unchanged, and the stirring temperature of the nucleophilic reaction is changed to 50 ℃.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
27.67g of tri-n-butylamine (purity 99%,0.148mol, molar ratio to difluoromethane chloride 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.49g of hydrogen chloride gas (purity 100%,0.123mol, molar ratio to difluoromethane chloride 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.45g of acetone, 6.71g of sodium cyanide solid (purity 90%,0.123mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.123mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording the weight gain of the reactor by 10.65g, heating to 50 ℃, stirring and reacting for 4.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 30.79g of a liquid alkali solution (purity 32%,0.246mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 27.93g of hydrogen peroxide solution (purity: 30%,0.246mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.80g, the gas phase detection purity is 99.35%, and the calculated yield is 65.55%.
Example 10
According to the implementation method and the embodiment 1, the material adding proportion is unchanged, and the stirring time of nucleophilic reaction is changed to 3 hours.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
into a 250ml four-necked flask equipped with a magnet, 27.88g of tri-n-butylamine (purity: 99%, molar ratio of 0.149mol to difluoromethane: 1.2:1) was charged, and 4.52g of hydrogen chloride gas (purity: 100%, molar ratio of 0.124mol to difluoromethane: 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
50.19g of acetone, 6.76g of sodium cyanide solid (purity 90%,0.124mol, molar ratio to difluoromethane 1:1) were added successively to a 250ml autoclave equipped with a magnet, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%, molar ratio of 0.124mol to sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording weight gain of the reactor by 10.73g, heating to 40 ℃, stirring and reacting for 3.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 31.02g of a liquid alkaline solution (purity 32%,0.248mol, molar ratio to difluoromethane: 2:1) was added with peristaltic pump at a rate of 1.0mL/min, and hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 28.14g of hydrogen peroxide solution (purity: 30%,0.248mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.72g, the gas phase detection purity is 99.53%, and the calculated yield is 64.46%.
Example 11
According to the implementation method and the embodiment 1, the material adding proportion is unchanged, and the stirring time of nucleophilic reaction is changed to 5 hours.
(1) Preparation of a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system:
26.74g of tri-n-butylamine (purity 99%,0.143mol, molar ratio to difluoromethane chloride: 1.2:1) was charged into a 250ml four-necked flask equipped with a magnet, and 4.34g of hydrogen chloride gas (purity 100%,0.119mol, molar ratio to difluoromethane chloride: 1:1) was charged into the four-necked flask. The temperature is controlled at room temperature in the inflation process, the reaction time is 2 hours, and tri-n-butyl ammonium chloride is generated by the reaction.
To a 250ml autoclave equipped with a magneton, 50.46g of acetone, 6.48g of sodium cyanide solid (purity 90%,0.119mol, molar ratio to difluoromethane 1:1) were successively added, and the autoclave was closed. Pumping the reacted tri-n-butyl ammonium chloride into an autoclave by a constant-flow high-pressure pump, wherein the dripping speed is 1.0mL/min, and the internal temperature is controlled below 25 ℃.
(2) Preparation of difluoroacetonitrile:
and (3) filling difluoromethane chloride (purity 100%,0.119mol, molar ratio of sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is 1:3.2) into the reactor, recording weight gain of the reactor by 10.29g, heating to 40 ℃, stirring and reacting for 5.0h, and ending the reaction.
(3) Preparation of difluoroacetic acid:
the temperature was lowered to room temperature, 29.75g of a liquid alkali solution (purity 32%,0.238mol, molar ratio to difluoromethane was 2:1) was added at a rate of 1.0mL/min with a peristaltic pump, and the mixture was hydrolyzed at room temperature for 2.0h; after the hydrolysis was completed, 26.98g of hydrogen peroxide solution (purity: 30%,0.238mol, molar ratio to difluoromethane: 2:1) was added at a rate of 1.0mL/min by a peristaltic pump, and quenched at room temperature for 2.0h.
After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid, wherein the quality is 7.53g, the gas phase detection purity is 99.34%, and the calculated yield is 65.50%.
As is clear from examples 1, 8 and 9, the purity and yield of the product are improved with the increase of the stirring temperature in the nucleophilic reaction stage, and the difference between the reaction results at 40℃and 50℃is small. As is clear from examples 1, 10 and 11, as the stirring time in the nucleophilic reaction stage was prolonged, the purity of the product was lowered, the yield was not greatly changed, and 3-hour stirring was the preferred choice. The process selection is preferred when stirring is performed at 40 ℃ for 3 hours to complete the reaction, in view of process efficiency and energy saving.
TABLE 1 summary of experimental data and experimental results for examples 1-11
TABLE 2 summary of experimental data and experimental results for examples 1-11 (Table 1, follow-up)
As can be seen from tables 1-2, the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system is prepared in a dipolar solvent such as acetone, difluoro-chloromethane is used as a starting material, and an alkaline environment is provided by the ion exchange system to catalyze R22 to generate difluoro-carbene. The ion exchange system promotes the sodium cyanide and tri-n-butyl ammonium chloride to generate anion exchange, promotes the cyanide and difluoro carbene to generate nucleophilic reaction to obtain difluoro acetonitrile, and obtains difluoro acetic acid through rapid hydrolytic oxidation, acidification and rectification. The process yield is above 62%, and the purity is more than 99%.
Preferred reaction conditions are: the molar ratio of tri-n-butylamine to difluoromethane chloride is 1.2:1, the molar ratio of hydrogen chloride to difluoromethane chloride is 1:1, the reaction time is 2h at room temperature, and the tri-n-butyl ammonium chloride is generated by the reaction. The molar ratio of sodium cyanide to difluoromethane is 1.2:1, acetone is used as a solvent, and tri-n-butyl ammonium chloride is added dropwise at the internal temperature of 25 ℃ at the rate of 1.0mL/min to prepare the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system. Then, the mixture is filled with difluoro-chloromethane gas, stirred for 3 hours at 40 ℃, the temperature is reduced to room temperature, liquid alkali solution with the molar ratio of the difluoro-chloromethane being 2:1 is added at the rate of 1.0mL/min, and the mixture is hydrolyzed for 2.0 hours at room temperature; after the hydrolysis is completed, a hydrogen peroxide solution with a molar ratio of 2:1 to difluoromethane chloride is added at a rate of 1.0mL/min, and the mixture is quenched at room temperature for 2.0h. After the reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and distilling and collecting fractions at 120-140 ℃ under normal pressure to obtain the difluoroacetic acid.
The difluoroacetic acid prepared in example 1 was subjected to gas chromatography, and the result of the gas chromatography is shown in fig. 1. The purity of the difluoroacetic acid obtained by distillation and collection of the fraction in the range of 120-140 ℃ under normal pressure reaches 99.37 percent, and the number of impurity peaks is 1. The main substance in the detected sample is 9.421min as seen in fig. 1, then the main substance with peak time 9.421min in fig. 1 is subjected to mass spectrum detection, the obtained mass spectrum is shown in fig. 2, and a computer automatically performs similarity matching on chemical structures possibly obtained in a database according to mass spectrum detection data, so that the peak matching result is that: the structure is difluoroacetic acid, the matching degree is 97, and finally the sample to be detected is difluoroacetic acid.
The invention provides a method for preparing difluoro acetic acid by nucleophilic reaction of difluoro chloromethane (R22) and a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system. Preparing a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system in a dipolar solvent such as acetone, taking difluoro-chloromethane as a starting material, providing an alkaline environment by the ion exchange system, and catalyzing R22 to generate difluoro carbene. The ion exchange system promotes the sodium cyanide and tri-n-butyl ammonium chloride to generate anion exchange, promotes the cyanide and difluoro carbene to generate nucleophilic reaction to obtain difluoro acetonitrile, and obtains difluoro acetic acid through rapid hydrolytic oxidation, acidification and rectification. The process yield is above 62%, and the purity is more than 99%. Compared with the prior process for preparing the difluoroacetic acid, the method has the advantages that:
1. reducing the side reaction of hydrocyanic acid self-polymerization; the reaction can realize higher yield only in the proportion of equimolar equivalent; the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system promotes the anion exchange of sodium cyanide, and can improve the solubility of cyanide sources in a dipolar solvent, thereby improving the possibility of participation of cyanide in nucleophilic attack, being beneficial to forward reaction and improving the defect of insoluble solid sodium cyanide. The solid-liquid opposite strain is changed into a homogeneous reaction, which is favorable for nucleophilic attack, improves the bonding efficiency of difluoro carbene and cyanogen, and finally improves the reaction efficiency and shortens the reaction time;
2. the reaction system is simple, the process for preparing the difluoroacetonitrile is carried out under the anhydrous condition, the competition of side reactions is avoided, the reaction selectivity is improved, and the reaction has better selectivity compared with the reaction in which sodium cyanide is directly used;
3. the reaction condition is mild, the reaction is carried out at normal temperature and normal pressure, and no special requirement is required for equipment; the reactant tri-n-butylamine can be recycled, the recycling step is simple, and the utilization rate is improved;
4. compared with the synthesis process using tetrafluoroethylene as raw material, the method has the advantages of high atomic utilization rate, high product yield and low cost.
The above embodiments are only for illustrating the technical solution of the present application, and are not limiting; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present application, and are intended to be included in the scope of the present application.
Claims (9)
1. A process for the preparation of difluoroacetic acid comprising the steps of:
(1) Filling hydrogen chloride gas into a container filled with tri-n-butylamine for reaction, and adding tri-n-butyl ammonium chloride which is a reaction product into a dipolar solvent containing sodium cyanide to form a sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system;
(2) Filling difluoro-chloromethane into the sodium cyanide-tertiary organic amine-hydrogen chloride ion exchange system, heating and stirring to catalyze the difluoro-chloromethane to generate difluoro-carbene, and carrying out nucleophilic reaction between the difluoro-carbene and cyanide in the ion exchange system to generate difluoro-acetonitrile;
(3) Cooling, adding liquid alkali for hydrolysis, adding hydrogen peroxide for quenching, and then filtering, rinsing, acidifying and distilling at normal pressure to obtain difluoro acetic acid;
in the step (1), the tri-n-butyl ammonium chloride is added in a dropwise manner, the dropwise adding rate is 1.0mL/min, and the system temperature is controlled to be lower than 25 ℃ during dropwise adding.
2. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: the mol ratio of tri-n-butylamine to difluoro chloromethane is 1.0-1.4:1.
3. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: the molar ratio of the sodium cyanide to the difluoro-chloromethane is 0.8-1.2:1.
4. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in the step (1), the charging process of the hydrogen chloride and the reaction process of the hydrogen chloride and the tri-n-butylamine are carried out at room temperature.
5. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in the step (1), the dipolar solvent is any one of acetone, acetonitrile or butanone.
6. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in the step (2), the temperature of heating and stirring is 30-50 ℃, and the reaction time is 3.0-5.0h.
7. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in step (3), the hydrolysis means: cooling the temperature to room temperature after the step (2) is finished; adding liquid alkali at a rate of 1.0-2.0mL/min, and hydrolyzing at room temperature for 2.0h; the liquid alkali is sodium hydroxide solution, and the molar ratio of the liquid alkali to the difluoro chloromethane is 2:1.
8. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in the step (3), the quenching means that hydrogen peroxide solution is added at a rate of 1.0-2.0mL/min after the hydrolysis reaction is finished, and the quenching is performed for 2.0h at room temperature, wherein the molar ratio of the hydrogen peroxide solution to the difluoromethane chloride is 2:1.
9. A process for the preparation of difluoroacetic acid as defined in claim 1 wherein: in the step (3), after the quenching reaction is finished, filtering and rinsing to obtain filtrate, adding concentrated sulfuric acid into the filtrate for acidification, and collecting fractions in the range of 120-140 ℃ by normal pressure distillation to obtain the difluoroacetic acid.
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