CN117658818B - A preparation method of 4-fluoro-3-nitrotrifluorotoluene - Google Patents
A preparation method of 4-fluoro-3-nitrotrifluorotoluene Download PDFInfo
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- CN117658818B CN117658818B CN202311457591.0A CN202311457591A CN117658818B CN 117658818 B CN117658818 B CN 117658818B CN 202311457591 A CN202311457591 A CN 202311457591A CN 117658818 B CN117658818 B CN 117658818B
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- HLDFCCHSOZWKAA-UHFFFAOYSA-N 1-fluoro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1F HLDFCCHSOZWKAA-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000003960 organic solvent Substances 0.000 claims abstract description 51
- 238000003682 fluorination reaction Methods 0.000 claims abstract description 37
- TZGFQIXRVUHDLE-UHFFFAOYSA-N 1-chloro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1Cl TZGFQIXRVUHDLE-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000002994 raw material Substances 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims description 59
- 238000007333 cyanation reaction Methods 0.000 claims description 38
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000706 filtrate Substances 0.000 claims description 29
- 229910052751 metal Inorganic materials 0.000 claims description 21
- 239000002184 metal Substances 0.000 claims description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 20
- 150000002825 nitriles Chemical class 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 17
- BQCWLXXZTCLGSZ-UHFFFAOYSA-N 2-nitro-4-(trifluoromethyl)benzonitrile Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1C#N BQCWLXXZTCLGSZ-UHFFFAOYSA-N 0.000 claims description 16
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 14
- 239000012065 filter cake Substances 0.000 claims description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 238000004821 distillation Methods 0.000 claims description 11
- 239000012295 chemical reaction liquid Substances 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 7
- 238000009835 boiling Methods 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 3
- 229910001512 metal fluoride Inorganic materials 0.000 claims description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002699 waste material Substances 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 3
- 239000011698 potassium fluoride Substances 0.000 description 24
- 239000000047 product Substances 0.000 description 19
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 16
- 238000001514 detection method Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 9
- 235000003270 potassium fluoride Nutrition 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000001103 potassium chloride Substances 0.000 description 5
- 235000011164 potassium chloride Nutrition 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000575 pesticide Substances 0.000 description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- -1 alkali metal cyanide Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- FGGUUGIYSOGQED-UHFFFAOYSA-N 1,2-oxazol-4-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)C=1C=NOC=1 FGGUUGIYSOGQED-UHFFFAOYSA-N 0.000 description 2
- FIGXUYQWSMOGBU-UHFFFAOYSA-N 5-cyclopropyl-1,2-oxazole Chemical compound C1CC1C1=CC=NO1 FIGXUYQWSMOGBU-UHFFFAOYSA-N 0.000 description 2
- 239000005571 Isoxaflutole Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- OYIKARCXOQLFHF-UHFFFAOYSA-N isoxaflutole Chemical compound CS(=O)(=O)C1=CC(C(F)(F)F)=CC=C1C(=O)C1=C(C2CC2)ON=C1 OYIKARCXOQLFHF-UHFFFAOYSA-N 0.000 description 2
- 229940088649 isoxaflutole Drugs 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 235000013024 sodium fluoride Nutrition 0.000 description 2
- 239000011775 sodium fluoride Substances 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000276 potassium ferrocyanide Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/14—Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Toxicology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明提供了一种4‑氟‑3‑硝基三氟甲苯的制备方法。本发明的制备方法包括以下步骤：在有机溶剂中，将4‑氯‑3‑硝基三氟甲苯和KF发生氟化反应，得4‑氟‑3‑硝基三氟甲苯；所述氟化反应的原料由所述有机溶剂、所述4‑氯‑3‑硝基三氟甲苯和所述KF组成。该制备方法不使用催化剂，也可实现产率高、纯度好且反应时间短；同时，操作便捷、成本低、废弃物污染少，更有利于工业化应用。 The present invention provides a method for preparing 4-fluoro-3-nitrobenzotrifluoride. The preparation method of the present invention comprises the following steps: in an organic solvent, 4-chloro-3-nitrobenzotrifluoride and KF are subjected to fluorination reaction to obtain 4-fluoro-3-nitrobenzotrifluoride; the raw material of the fluorination reaction is composed of the organic solvent, the 4-chloro-3-nitrobenzotrifluoride and the KF. The preparation method does not use a catalyst, and can also achieve high yield, good purity and short reaction time; at the same time, it is easy to operate, low in cost, less waste pollution, and more conducive to industrial application.
Description
Technical Field
The invention belongs to the field of organic chemistry, and relates to a preparation method of 4-fluoro-3-nitrobenzotrifluoride.
Background
The molecular formula of the 2-nitro-4-trifluoromethyl benzonitrile is C 8H3F3N2O2, the relative molecular weight is 216.1, the melting point is 44-47 ℃, the boiling point is 156-158 ℃ and 18mm Hg (lith.), the density is 1.56g/mL, and the product is yellow crystalline solid at room temperature. 2-nitro-4-trifluoromethylbenzonitrile is widely used in the fields of medicine, pesticides, chemical industry, etc., and is an important intermediate for synthesizing pesticide 4-benzoylisoxazole, isoxaflutole, herbicide 5-cyclopropylisoxazole, the synthesis of the above mentioned compounds and intermediates thereof is disclosed in patent CN 1359372a, and also mentioned in european patent application.
Patent publication No. CN 1359372A discloses a method for synthesizing 2-nitro-4-trifluoromethyl benzonitrile, which comprises the steps of preparing 4-chloro-3-nitro-benzotrifluoride and cuprous cyanide, a phase transfer catalyst or alkali metal cyanide, cuprous bromide and a phase transfer catalyst or preparing 2-nitro-4-trifluoromethyl benzonitrile in the presence of metal lithium salt in an organic solvent, wherein the preparation method has high cost, operation redundancy, various raw material types and high after-treatment recycling difficulty.
4-Fluoro-3-nitrobenzotrifluoride molecular formula C 7H3F4NO2, relative molecular weight 209.1, relative density 1.494, boiling point 92 deg.C (15 mmHg), refractive index 1.4620, and light yellow green liquid at room temperature. 4-fluoro-3-nitro benzotrifluoride is an important intermediate, and is applied to the fields of medicine, pesticide, chemical organic synthesis and the like to synthesize pesticides 4-benzoyl isoxazole, isoxaflutole, herbicide 5-cyclopropyl isoxazole and the like.
In patent U.S. Pat. No. 3, 4424396 and J, the synthesis of 4-fluoro-3-nitrobenzotrifluoride from the same starting material 4-chloro-3-nitrobenzotrifluoride is reported, for example, journal of Organic Chemistry,1991, vol.56, #22, p.6406-6411, which discloses the synthesis of 4-fluoro-3-nitrobenzotrifluoride from sulfolane with KF prepared by the "spray drying" process (material droplets after atomization, surface area increase) under the catalysis of tetramethyl ammonium chloride, with 80% yield in the presence of the starting materials of the particular process and phase transfer catalyst, as well as ADVANCED SYNTHESIS AND CATALYSIS,2008, vol.350, #17, p.2677-2682 with KF, bis (diphenyl phosphine) imide chloride added to DMSO, with a yield of 72%. The target product can be synthesized only by adding the catalyst into the consulted literature, and the synthetic route has high cost and complex raw materials.
Disclosure of Invention
In order to solve the problems of high production cost, serious three-waste pollution, difficult post-treatment and the like in the prior art, the invention develops a preparation method for preparing 4-fluoro-3-nitrobenzotrifluoride, which has high yield, good purity and short reaction time, and has the advantages of simple process, convenient operation, low cost, less waste pollution and more contribution to industrialized application.
The invention provides a preparation method of 4-fluoro-3-nitro benzotrifluoride, which comprises the following steps of carrying out fluorination reaction on 4-chloro-3-nitro benzotrifluoride and KF in an organic solvent to obtain 4-fluoro-3-nitro benzotrifluoride;
The raw materials of the fluorination reaction consist of the organic solvent, the 4-chloro-3-nitrobenzotrifluoride and the KF.
In the fluorination reaction, the organic solvent may be a conventional organic solvent for fluorination reaction in the art, preferably an aprotic polar solvent, more preferably DMF, DMA, acetonitrile, sulfolane or DMSO, for example sulfolane or DMF.
In the fluorination reaction, the molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent may be in a conventional amount in the art of fluorination reaction, preferably 1.0 to 2.5mol/L, more preferably 1.4 to 2.4mol/L, for example 1.9mol/L.
In the fluorination reaction, the molar ratio of KF to 4-chloro-3-nitrobenzotrifluoride may be in an amount conventional in the art for fluorination reactions, preferably (1.0-2.0): 1, more preferably (1.0-1.5): 1, for example 1.3:1.
In the fluorination reaction, the reaction temperature of the fluorination reaction may be a temperature conventional in the art for fluorination reactions, preferably 25 ℃ to 250 ℃, more preferably 130 to 180 ℃, for example 150 to 180 ℃.
In the fluorination reaction, the progress of the fluorination reaction is monitored by a detection method conventional in the art (e.g., GC monitoring), preferably by terminating the concentration of the 4-chloro-3-nitrobenzotrifluoride in the reaction solution at less than 1%.
In the fluorination reaction, the 4-chloro-3-nitrobenzotrifluoride is added in a mode of adding the 4-chloro-3-nitrobenzotrifluoride into a mixed solution of KF and the organic solvent, wherein the adding time is 1-10h, preferably 3-7h, more preferably 5-7h.
In the fluorination reaction, the post-treatment can be referred to a conventional operation method of the post-treatment in the art, and preferably, the post-treatment comprises the steps of:
(1) Filtering the reaction liquid after the fluorination reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is KF and/or KCl;
(2) And distilling the filtrate to obtain the 4-fluoro-3-nitrobenzotrifluoride and the organic solvent.
Preferably, the distillation is reduced pressure distillation, for example reduced pressure distillation.
In the fluorination reaction, when the boiling point of the organic solvent is higher than 209.6 ℃, the organic solvent can be left in a container for continuous use after the 4-fluoro-3-nitrobenzotrifluoride is obtained by distillation in the post-treatment step (2).
In the fluorination reaction, the organic solvent is DMF or sulfolane, the molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent is 1.9mol/L, the molar ratio of the KF to the 4-chloro-3-nitrobenzotrifluoride is 1.3:1, the reaction temperature of the fluorination reaction is 150-180 ℃, and the adding time is 5-7h.
The invention also provides a preparation method of the 2-nitro-4-trifluoromethyl benzonitrile, which comprises the following steps:
(1) The fluorination reaction occurs under the conditions and parameters of any one of the present invention;
(2) Carrying out cyanidation reaction on 4-fluoro-3-nitrobenzotrifluoride and metal cyanide to obtain 2-nitro-4-trifluoromethyl benzonitrile;
in the cyanation reaction, the cyanation reaction may occur in the presence of an organic solvent or in the absence of a solvent.
In the cyanation reaction, the organic solvent is an aprotic polar solvent.
In the cyanation reaction, the temperature of the cyanation reaction is 150-180 ℃.
In the cyanation reaction, the boiling point of the organic solvent is higher than or equal to the cyanation reaction temperature.
In the cyanation reaction, the raw materials of the cyanation reaction consist of the organic solvent, the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt, or consist of the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt.
In the cyanation reaction, the organic solvent is DMSO, DMF, DMA or sulfolane, preferably DMSO or DMF.
In the cyanation reaction, the metal cyanide salt may be a conventional metal cyanide salt of cyanation reaction in the art, preferably KCN, naCN, cuCN, potassium ferrocyanide and potassium ferricyanide, more preferably KCN, naCN, e.g. KCN.
In the cyanation reaction, when the organic solvent is DMF, the cyanation reaction temperature is preferably 150 ℃.
In the cyanation reaction, when the cyanation reaction occurs in the presence of an organic solvent, the molar volume ratio of the 4-fluoro-3-nitrobenzotrifluoride to the organic solvent may be in a conventional amount in the cyanation reaction, preferably 1.0 to 2.6mol/L, for example 1.5 to 2.1mol/L.
In the cyanation reaction, the molar ratio of cyano groups to 4-fluoro-3-nitrobenzotrifluoride in the metal cyanide salt may be in an amount conventional in the cyanation reaction, preferably (0.95-1.0): 1.0, more preferably (0.95-0.97): 1.0, for example 0.95:1.0 or 0.96:1.0.
In the cyanation reaction, the progress of the cyanation reaction is monitored by a detection method (for example, GC) conventional in the art, preferably by ending in a concentration of the 4-fluoro-3-nitrobenzotrifluoride of less than 0.1% in the reaction liquid.
In the cyanation reaction, the post-treatment can be referred to a conventional operation method of the post-treatment in the art, and preferably, the post-treatment comprises the steps of:
(1) Filtering the reaction liquid after the cyanidation reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is metal fluoride;
(2) And distilling the filtrate, and recovering the organic solvent to obtain the 2-nitro-4-trifluoromethyl benzonitrile.
In the post-treatment, the distillation is reduced pressure distillation, for example, reduced pressure distillation.
In a preferred scheme, the raw materials for the cyanation reaction comprise the organic solvent, the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt, wherein the organic solvent is DMSO or DMF, the metal cyanide salt is KCN, the molar volume ratio of the 4-fluoro-3-nitrobenzotrifluoride to the organic solvent is 1.5-2.1mol/L, and the molar ratio of cyano group in the metal cyanide salt to the 4-fluoro-3-nitrobenzotrifluoride is 0.95:1.0 or 0.96:1.0.
In a certain preferred scheme, the raw materials for the cyanation reaction consist of the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt, wherein the metal cyanide salt is KCN, and the molar ratio of cyano to the 4-fluoro-3-nitrobenzotrifluoride in the metal cyanide salt is 0.95:1.0 or 0.96:1.0.
The above preferred conditions can be arbitrarily combined on the basis of not deviating from the common knowledge in the art, and thus, each preferred embodiment of the present invention can be obtained.
The term "boiling point" as used herein refers to the temperature at which the pure material boils at 1 normal atmospheric pressure.
The reagents and materials used in the present invention are commercially available. KF manufacturer, allatin, AR, powder, 99%.
The preparation method disclosed by the invention has the positive progress effects that (1) the product prepared by the preparation method disclosed by the invention is high in yield and good in purity, (2) the short reaction time can be realized without using a catalyst, and (3) the preparation method is simple in process, convenient to operate, low in cost and less in waste pollution, and is more beneficial to industrial application.
Detailed Description
The invention is further illustrated by means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Example 1
The reaction equation is:
Experimental feed table:
150.8g of potassium fluoride and 1350.0g of sulfolane as a solvent are added into a 2L reaction flask, the temperature is raised to 150 ℃, 450.0g of 4-chloro-3-nitrobenzotrifluoride as a raw material is dropwise added for 5 hours, the reaction is carried out at 150 ℃ in a heat-preserving way, the reaction progress is monitored by GC, when the raw material of 4-chloro-3-nitrobenzotrifluoride is less than or equal to 1.0 percent, namely, the reaction is carried out for 10 hours, the temperature is reduced to room temperature, the generated potassium chloride and potassium fluoride are removed by filtration, the filtrate is rectified, the product is rectified, the anhydrous pale yellow liquid of 4-fluoro-3-nitrobenzotrifluoride is obtained, the purity of the product is 99.0 percent through GC detection, the kettle substrate is recovered and reused, and the yield is 90.0 percent.
Hydrogen spectrum analysis ：1H NMR(600MHz,CDC13)δ8.59-8.44(m,2H),7.65(dd,J＝9.0,2.2Hz,1H),7.03(d,J＝9.0Hz,1H),4.03-3.99(m,2H),3.60-3.56(m,2H).
GC analysis method
The sample preparation method comprises sampling and filtering, and sampling filtrate.
Experimental feed table:
366.0g of 4-fluoro-3-nitrobenzotrifluoride, 108.1g of potassium cyanide and 1098.0g of solvent DMF are added into a 2L reaction flask, the temperature is raised to 150 ℃, the reaction progress is monitored by GC, the temperature is kept for 8-12 h until the reaction of the raw material 4-fluoro-3-nitrobenzotrifluoride is finished, the temperature is reduced to room temperature, the filtration and the drying are carried out, and 91.8g of KF solid is obtained in total and recycled. And (3) recovering DMF and 4-fluoro-3-nitrobenzotrifluoride from the filtrate, and carrying out post-treatment to obtain 2-nitro-4-trifluoromethyl benzonitrile, wherein the purity of the product is 99.4% and the yield is 90.0% through GC detection.
Hydrogen analysis 1H NMR (400 MHz, CDCl 3): delta 8.60 (s, 1H), 8.14-8.04 (m, 2H).
Experimental feed table:
91.8 g of dry filter cake (ground into powder, KF solid recovered in the last step) is added into a 2L reaction flask, 825.6g of solvent sulfolane is heated to 150 ℃, 275.2g of raw material 4-chloro-3-nitrobenzotrifluoride is dripped into the reaction flask for 5 hours, the reaction is carried out at 150 ℃ in a heat-preserving way, the reaction progress is monitored by GC, namely the reaction is carried out for 8-12 hours, when the raw material 4-chloro-3-nitrobenzotrifluoride is less than or equal to 1.0%, the temperature is reduced to room temperature, the filtration is carried out, the filtrate is rectified, the product is rectified, the anhydrous pale yellow liquid 4-fluoro-3-nitrobenzotrifluoride is obtained, the purity of the product is 99.0% through GC detection, the kettle substrate is recovered and reused, and the yield is 90.0%.
Hydrogen spectrum analysis ：1H NMR(600MHz,CDC13)δ8.59-8.44(m,2H),7.65(dd,J＝9.0,2.2Hz,1H),7.03(d,J＝9.0Hz,1H),4.03-3.99(m,2H),3.60-3.56(m,2H).
Example 2
The reaction equation is:
Experimental feed table:
139.2g of potassium fluoride and 1350.0g of solvent sulfolane are added into a 2L reaction flask, the temperature is raised to 150 ℃, 450.0g of raw material 4-chloro-3-nitrobenzotrifluoride is dripped for 4 hours, the reaction is carried out at 150 ℃ in a heat preservation mode, the reaction progress is monitored through GC, when the raw material 4-chloro-3-nitrobenzotrifluoride is less than or equal to 1.0 percent, namely, the reaction is carried out for 10 hours, the temperature is reduced to room temperature, generated potassium chloride and potassium fluoride are removed through filtration, filtrate is rectified, products are rectified, anhydrous pale yellow liquid 4-fluoro-3-nitrobenzotrifluoride is obtained, the purity of the products is 99.1 percent through GC detection, kettle substrates are recycled, and the yield is 88.0 percent. The hydrogen spectrum is the same as in example 1.
Experimental feed table:
360.0g of 4-fluoro-3-nitrobenzotrifluoride, 107.4g of potassium cyanide and 1080.0g of solvent acetonitrile are added into a 2L reaction flask, the temperature is raised to 80 ℃, the reaction progress is monitored by GC, the temperature is kept for 10 to 12 hours until the reaction of the raw material 4-fluoro-3-nitrobenzotrifluoride is finished, the reaction is not carried out any more, the temperature is reduced to room temperature, the filtration and the drying are carried out, 92.3g of KF solid is obtained in total, and the recovery and the application are carried out. The filtrate is used for recovering acetonitrile and 4-fluoro-3-nitrobenzotrifluoride, and 2-nitro-4-trifluoromethyl benzonitrile is obtained after post-treatment, and the purity of the product is 99.3 percent and the yield is 50.0 percent through GC detection. The hydrogen spectrum is the same as in example 1.
Example 3
The reaction equation is:
Experimental feed table:
150.8g of potassium fluoride, 1350.0g of sulfolane serving as a solvent, 450.0g of 4-chloro-3-nitrobenzotrifluoride serving as a raw material, heating to 180 ℃ for heat preservation reaction, monitoring the reaction progress through GC, cooling to room temperature after the reaction is carried out for 10 hours until the raw material of 4-chloro-3-nitrobenzotrifluoride is less than or equal to 1.0%, filtering to remove generated potassium chloride and potassium fluoride, rectifying filtrate, rectifying a distilled product to obtain anhydrous pale yellow liquid of 4-fluoro-3-nitrobenzotrifluoride, detecting through GC, ensuring that the purity of the product is 99.2%, recycling kettle substrates, and ensuring that the yield is 85.0%. The hydrogen spectrum is the same as in example 1.
Experimental feed table:
355.0g of 4-fluoro-3-nitrobenzotrifluoride and 104.8g of potassium cyanide are added into a 2L reaction flask, the temperature is raised to 150 ℃, the reaction progress is monitored by GC, the temperature is kept for 8-12h until the reaction of the raw material 4-fluoro-3-nitrobenzotrifluoride is finished, the temperature is reduced to room temperature, the filtration and the drying are carried out, 90.8g of KF solid is obtained in total, and the KF solid is recovered for reuse. 4-fluoro-3-nitro benzotrifluoride is recovered from the filtrate, and the 2-nitro-4-trifluoromethyl benzonitrile is obtained after post-treatment, and the purity of the product is 99.1 percent and the yield is 70.0 percent through GC detection. The hydrogen spectrum is the same as in example 1.
Example 4
The reaction equation is:
Experimental feed table:
150.8g of potassium fluoride and 1350.0g of sulfolane as a solvent are added into a 2L reaction flask, the temperature is raised to 130 ℃, 450.0g of 4-chloro-3-nitrobenzotrifluoride as a raw material is dropwise added for 5 hours, the reaction is carried out at the temperature of 130 ℃, the reaction progress is monitored by GC, when the raw material of 4-chloro-3-nitrobenzotrifluoride is less than or equal to 1 percent, namely, the reaction is carried out for 8-12 hours, the temperature is reduced to room temperature, the generated potassium chloride and potassium fluoride are removed by filtration, the filtrate is rectified, the product is rectified, the anhydrous pale yellow liquid of 4-fluoro-3-nitrobenzotrifluoride is obtained, the product purity is 99.4 percent through GC detection, the kettle substrate is recovered and reused, and the yield is 75.0 percent. The hydrogen spectrum is the same as in example 1.
Experimental feed table:
Adding 313g of 4-fluoro-3-nitrobenzotrifluoride, 93.4g of potassium cyanide and 782.5g of solvent DMSO into a 2L reaction flask, heating to 180 ℃, monitoring the reaction progress through GC, preserving heat for 10-12 h until the reaction of the raw material 4-fluoro-3-nitrobenzotrifluoride is finished, cooling to room temperature, filtering, drying, obtaining 81.6g of KF solid crude product in total, and recycling. DMSO is recovered from the filtrate, and 2-nitro-4-trifluoromethyl benzonitrile is obtained after post treatment, and the purity of the product is 99.2 percent and the yield is 85.0 percent through GC detection. The hydrogen spectrum is the same as in example 1.
Example 5
The reaction equation is:
Experimental feed table:
366.0g of 4-fluoro-3-nitrobenzotrifluoride and 81.5g of NaCN were introduced into a 2L reaction flask. 1098.0g of solvent DMF is heated to 150 ℃, the reaction progress is monitored by GC, the temperature is kept for 10 hours until the reaction of the raw material 4-fluoro-3-nitrobenzotrifluoride is finished, the reaction is not carried out, the temperature is reduced to room temperature, the filtration and the drying are carried out, and 91.8g of KF solid is obtained and recovered for reuse. DMF and 4-fluoro-3-nitrobenzotrifluoride are recovered from the filtrate, and the 2-nitro-4-trifluoromethyl benzonitrile is obtained after post-treatment, 332.8g, and the purity of the product is 99% and the yield is 88.0% through GC detection. The hydrogen spectrum is the same as in example 1.
Comparative example 1
The feeding amount is as follows:
Experimental operation:
To a 250mL reaction flask, 10.9g of sodium fluoride, 135.0g of sulfolane as a solvent, heating to 150 ℃, dropwise adding 45.0g of 4-chloro-3-nitrobenzotrifluoride as a raw material for 5 hours, and carrying out heat preservation reaction at 150 ℃, wherein the GC monitors the progress of the reaction, the raw material percentages are 99.6%, and no product peak exists basically.
Conclusion NaF did not react.
Claims (12)
1. The preparation method of the 2-nitro-4-trifluoromethyl benzonitrile is characterized by comprising the following steps of:
(1) In an organic solvent, carrying out fluorination reaction on 4-chloro-3-nitrobenzotrifluoride and KF to obtain 4-fluoro-3-nitrobenzotrifluoride;
,
the raw materials of the fluorination reaction consist of the organic solvent, the 4-chloro-3-nitrobenzotrifluoride and the KF;
(2) Carrying out cyanidation reaction on 4-fluoro-3-nitrobenzotrifluoride and metal cyanide to obtain 2-nitro-4-trifluoromethyl benzonitrile;
;
The temperature of the cyanidation reaction is 150-180 ℃;
the cyanation reaction occurs in the presence or absence of an organic solvent;
in the cyanation reaction, the organic solvent is DMSO or DMF;
in the cyanation reaction, the metal cyanide salt is KCN or NaCN.
2. The method of claim 1, wherein the fluorination reaction satisfies one or more of the following conditions:
① The molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent is 1.0-2.5mol/L;
② The molar ratio of KF to 4-chloro-3-nitrobenzotrifluoride is (1.0-2.0) 1;
③ The reaction temperature of the fluorination reaction is 25-250 ℃;
④ The adding mode of the 4-chloro-3-nitrobenzotrifluoride is that the 4-chloro-3-nitrobenzotrifluoride is added into the mixed solution of KF and the organic solvent;
⑤ The post-treatment of the fluorination reaction comprises the following steps:
(1) Filtering the reaction liquid after the fluorination reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is KF and/or KCl;
(2) And distilling the filtrate to obtain the 4-fluoro-3-nitrobenzotrifluoride and the organic solvent.
3. The method of claim 2, wherein the fluorination reaction satisfies one or more of the following conditions:
① The organic solvent is DMF, DMA, acetonitrile, sulfolane or DMSO;
② The molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent is 1.4-2.4mol/L;
③ The molar ratio of KF to 4-chloro-3-nitrobenzotrifluoride is (1.0-1.5) 1;
④ The reaction temperature of the fluorination reaction is 130-180 ℃;
⑤ The adding time is 1-10h;
⑥ The distillation is reduced pressure distillation.
4. A method of preparation as claimed in claim 3 wherein the fluorination reaction meets one or more of the following conditions:
① The organic solvent is DMF or sulfolane;
② The molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent is 1.9 mol/L;
③ The molar ratio of KF to 4-chloro-3-nitrobenzotrifluoride is 1.3:1;
④ The reaction temperature of the fluorination reaction is 150-180 ℃;
⑤ The time of the addition is 3-7h.
5. The process of claim 4 wherein said fluorination reaction is carried out for a period of from 5 to 7 hours.
6. The method of claim 1, wherein the post-treatment of the fluorination reaction comprises the steps of:
(1) Filtering the reaction liquid after the fluorination reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is KF and/or KCl;
(2) And rectifying the filtrate under reduced pressure to obtain the 4-fluoro-3-nitrobenzotrifluoride and the organic solvent.
7. The process according to claim 4, wherein in the fluorination reaction, the organic solvent is DMF or sulfolane, the molar volume ratio of the 4-chloro-3-nitrobenzotrifluoride to the organic solvent is 1.9 mol/L, the molar ratio of KF to the 4-chloro-3-nitrobenzotrifluoride is 1.3:1, the reaction temperature of the fluorination reaction is 150 to 180 ℃, and the addition time is 5 to 7 hours.
8. The method of claim 1, wherein the cyanation reaction occurs in the presence or absence of an organic solvent, wherein the organic solvent is DMSO or DMF;
The temperature of the cyanidation reaction is 150-180 ℃;
The boiling point of the organic solvent is greater than or equal to the temperature of the cyanation reaction.
9. The method of preparation of claim 8, wherein the cyanation reaction satisfies one or more of the following conditions:
① The raw materials of the cyanation reaction consist of the organic solvent, the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt, or the 4-fluoro-3-nitrobenzotrifluoride and the metal cyanide salt;
② The molar ratio of cyano to 4-fluoro-3-nitrobenzotrifluoride in the metal cyanide salt is (0.95-1.0) 1.0;
③ When the cyanation reaction occurs in the presence of an organic solvent, the molar volume ratio of the 4-fluoro-3-nitrobenzotrifluoride to the organic solvent is 1.0-2.6mol/L;
④ The post-treatment of the cyanation reaction comprises the following steps:
(1) Filtering the reaction liquid after the cyanidation reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is metal fluoride;
(2) And distilling the filtrate, and recovering the organic solvent to obtain the 2-nitro-4-trifluoromethyl benzonitrile.
10. The method of preparation of claim 9, wherein the cyanation reaction satisfies one or more of the following conditions:
① The molar ratio of cyano to 4-fluoro-3-nitrobenzotrifluoride in the metal cyanide salt is (0.95-0.97): 1.0;
② When the cyanation reaction occurs in the presence of an organic solvent, the molar volume ratio of the 4-fluoro-3-nitrobenzotrifluoride to the organic solvent is 1.5-2.1mol/L;
③ In the post-treatment, the distillation is reduced pressure distillation.
11. The method of preparation of claim 10, wherein the cyanation reaction satisfies one or more of the following conditions:
① When the organic solvent is DMF, the cyanation reaction temperature is 150 ℃;
② The metal cyanide salt is KCN;
③ The molar ratio of cyano to 4-fluoro-3-nitrobenzotrifluoride in the metal cyanide salt is 0.95:1.0 or 0.96:1.0.
12. The method of claim 8, wherein the post-treatment of the cyanation reaction comprises the steps of:
(1) Filtering the reaction liquid after the cyanidation reaction is finished, and recovering filtrate and a filter cake, wherein the filtrate is a crude product, and the filter cake is metal fluoride;
(2) And (3) rectifying the filtrate under reduced pressure, and recovering the organic solvent to obtain the 2-nitro-4-trifluoromethyl benzonitrile.
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| US6635780B1 (en) * | 1998-10-13 | 2003-10-21 | Bayer Cropscience S.A. | Chemical processes |
| CN1994986A (en) * | 2006-12-29 | 2007-07-11 | 天津市筠凯化工科技有限公司 | Process for preparing 3,4-difluoro-benzotrifluoride |
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| DE19529973A1 (en) * | 1995-08-16 | 1997-02-20 | Hoechst Ag | Process for the preparation of ortho-nitrobenzonitriles |
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| CN1994986A (en) * | 2006-12-29 | 2007-07-11 | 天津市筠凯化工科技有限公司 | Process for preparing 3,4-difluoro-benzotrifluoride |
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