CN117623897A - Preparation method of o-trifluoromethyl benzoic acid - Google Patents
Preparation method of o-trifluoromethyl benzoic acid Download PDFInfo
- Publication number
- CN117623897A CN117623897A CN202311505931.2A CN202311505931A CN117623897A CN 117623897 A CN117623897 A CN 117623897A CN 202311505931 A CN202311505931 A CN 202311505931A CN 117623897 A CN117623897 A CN 117623897A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- sulfuric acid
- preparation
- concentration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- FBRJYBGLCHWYOE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(F)(F)F FBRJYBGLCHWYOE-UHFFFAOYSA-N 0.000 title abstract description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 108
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 64
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 14
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 11
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 5
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 230000007062 hydrolysis Effects 0.000 claims description 16
- 238000006460 hydrolysis reaction Methods 0.000 claims description 16
- 239000007864 aqueous solution Substances 0.000 claims description 14
- 235000010265 sodium sulphite Nutrition 0.000 claims description 10
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 5
- 239000000243 solution Substances 0.000 description 20
- 239000002994 raw material Substances 0.000 description 16
- 238000001816 cooling Methods 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 6
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 5
- 238000004321 preservation Methods 0.000 description 5
- QBAYIBZITZBSFO-UHFFFAOYSA-N 2-(trifluoromethyl)benzamide Chemical compound NC(=O)C1=CC=CC=C1C(F)(F)F QBAYIBZITZBSFO-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- BGVGHYOIWIALFF-UHFFFAOYSA-N 1-fluoro-2-(trifluoromethyl)benzene Chemical compound FC1=CC=CC=C1C(F)(F)F BGVGHYOIWIALFF-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- SOZGHDCEWOLLHV-UHFFFAOYSA-N 2-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC=CC=C1C#N SOZGHDCEWOLLHV-UHFFFAOYSA-N 0.000 description 1
- AWSZRJQNBMEZOI-UHFFFAOYSA-N 2-methoxyethyl 2-(4-tert-butylphenyl)-2-cyano-3-oxo-3-[2-(trifluoromethyl)phenyl]propanoate Chemical compound C=1C=C(C(C)(C)C)C=CC=1C(C#N)(C(=O)OCCOC)C(=O)C1=CC=CC=C1C(F)(F)F AWSZRJQNBMEZOI-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 239000005655 Cyflumetofen Substances 0.000 description 1
- 239000005783 Fluopyram Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- KVDJTXBXMWJJEF-UHFFFAOYSA-N fluopyram Chemical compound ClC1=CC(C(F)(F)F)=CN=C1CCNC(=O)C1=CC=CC=C1C(F)(F)F KVDJTXBXMWJJEF-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- -1 o-trifluoromethyl dichlorobenzyl Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of o-trifluoromethyl benzoic acid. The invention provides a preparation method of a compound shown in a formula I, which comprises the following steps: (1) Hydrolyzing a compound of formula III in the presence of sulfuric acid in the absence of an organic solvent; (2) And (3) reacting the reaction liquid obtained in the step (1) with sodium nitrite to obtain the compound shown in the formula I. The preparation method provided by the invention provides a novel method for synthesizing o-trifluoromethyl benzoic acid, and has high yield and purity and convenient operation; meanwhile, no organic solvent is needed, and the method is more in line with green chemistry.
Description
Technical Field
The invention belongs to the field of organic synthesis, and provides a novel method for preparing o-trifluoromethyl benzoic acid.
Background
O-trifluoromethyl benzoic acid is an important intermediate or raw material in the field of fine chemical engineering, and as the raw material, o-trifluoromethyl benzoic acid is used as a key intermediate for synthesizing broad-spectrum bactericides fluopyram and cyflumetofen, and along with the wide use of the bactericides, the demand of the o-trifluoromethyl benzoic acid is also increasing. In the patents CN114436810a and CN103274929a, a preparation method of o-trifluoro benzoic acid is mentioned, and a common preparation method is that o-trifluoro methyl toluene is used as a raw material, and is subjected to substitution reaction with chlorine gas, then hydrolyzed into o-trifluoro methyl benzaldehyde, and then oxidized into o-trifluoro methyl benzoic acid. Two routes for oxidizing o-trifluoromethyl benzaldehyde into o-trifluoro-benzoic acid have industrial value; in addition, o-fluorobenzotrifluoride is also widely applied to the fields of medicine, pesticide, chemical industry and the like.
Route one: oxidizing o-trifluoromethyl benzaldehyde into o-trifluoromethyl benzoic acid by hydrogen peroxide
Route two: the raw material is o-trifluoromethyl benzaldehyde as the same as the first route, and TEMPO is used as an oxidant
Route three: o-trifluoromethyl dichlorobenzyl is taken as a raw material, and is hydrolyzed in nitric acid solution to obtain o-trifluoromethyl benzaldehyde, and then in-situ oxidation is carried out to obtain o-trifluoromethyl benzoic acid
O-trifluoromethyl benzoic acid with molecular formula of C 8 H 5 F 3 O 2 The relative molecular weight is 190.1, the melting point is 110-112 ℃, the boiling point is 248 ℃, and the powder is white solid.
Disclosure of Invention
In the prior art, o-trifluoromethyl benzonitrile is not used for synthesizing o-trifluoromethyl benzoamide and o-trifluoromethyl benzoic acid. Because of the effect of trifluoromethyl, the two raw materials are difficult to directly hydrolyze to synthesize the target product o-trifluoromethyl benzoic acid. The preparation method provided by the invention provides a novel method for synthesizing o-trifluoromethyl benzoic acid, and has high yield and purity and convenient operation; meanwhile, no organic solvent is needed, and the method is more in line with green chemistry.
The invention provides a preparation method of a compound shown in a formula I, which comprises the following steps:
(1) Hydrolyzing a compound of formula III in the presence of sulfuric acid in the absence of an organic solvent;
(2) The reaction liquid obtained in the step (1) reacts in the presence of sodium nitrite to obtain the compound shown in the formula I,
the concentration of the sulfuric acid is 75-90%;
the reaction temperature in the step (1) is 100-150 ℃;
the reaction temperature in the step (2) is 80-140 ℃.
In one embodiment, the concentration of sulfuric acid is 80 to 85%, preferably 80%.
In one embodiment, the sodium nitrite is an aqueous solution of sodium nitrite having a concentration of 5 to 45%, preferably 20 to 30%, for example 20%.
In one embodiment, the molar ratio of the compound of formula III to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), e.g., 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6.
In one embodiment, the sulfuric acid is added in an amount of 2 to 10ml/kg, preferably 4 to 6ml/kg, for example 5ml/kg, relative to the compound of formula III.
In one embodiment, the reaction time in step (1) is 1 to 8 hours, preferably 3 hours.
In one embodiment, the reaction time in step (2) is 2 to 10 hours, preferably 5 to 6 hours.
In one embodiment, the reaction temperature in step (1) is 140 to 150 ℃, preferably 140 ℃.
In one embodiment, the reaction temperature in step (2) is 120 to 140 ℃, preferably 120 ℃.
In one embodiment, the preparation method comprises the following steps:
(1) In the absence of an organic solvent, hydrolyzing the compound of formula III in the presence of 80% sulfuric acid at 140 ℃;
(2) The reaction liquid obtained in the step (1) reacts with 20% sodium nitrite to obtain the compound shown in the formula I, and the reaction temperature is 120 ℃.
In one embodiment, the preparation method further comprises the following steps: stirring, cooling, and suction filtering to obtain the compound of formula I.
The invention also provides a preparation method of the compound shown in the formula II, which comprises the following steps: hydrolyzing the compound of the formula III in the presence of sulfuric acid under the condition of no organic solvent to obtain the compound of the formula II,
the concentration of the sulfuric acid is 75-90%;
the temperature of the hydrolysis is 100-150 ℃.
In one embodiment, the concentration of sulfuric acid is 80 to 85%, preferably 80%.
In one embodiment, the molar ratio of the compound of formula III to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), e.g., 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6.
In one embodiment, the amount of sulfuric acid added is 2-10ml/kg, preferably 4-6ml/kg, for example 5ml/kg, relative to the compound of formula III.
In one embodiment, the hydrolysis time is 1 to 8 hours, preferably 3 hours.
In one embodiment, the hydrolysis temperature is 140 to 150 ℃, preferably 140 ℃.
In one embodiment, the preparation method comprises the following steps: in the absence of organic solvents, the compounds of formula III are hydrolysed in the presence of 80% sulfuric acid at a temperature of 140 ℃.
The invention also provides a preparation method of the compound shown in the formula I, which comprises the following steps: (1) Hydrolyzing the compound of the formula III in the presence of sulfuric acid in the absence of an organic solvent to obtain a compound of the formula II,
the concentration of the sulfuric acid is 75-90%;
the temperature of the hydrolysis is 100-150 ℃;
(2) Hydrolyzing the compound of the formula II in the presence of acid and sodium nitrite to obtain a compound of the formula I,
the acid is sulfuric acid or hydrochloric acid;
the concentration of sulfuric acid is 20-80% when the acid is sulfuric acid;
when the acid is hydrochloric acid, the concentration of the hydrochloric acid is 30-35%.
In one embodiment, in step (2), the acid is sulfuric acid or hydrochloric acid; when the acid is sulfuric acid, the concentration of the acid is 20-80%; the concentration of the acid is 30-35% when the acid is hydrochloric acid.
In one embodiment, in step (2), the acid is sulfuric acid, preferably 20 to 80% sulfuric acid, more preferably 30 to 50% sulfuric acid, for example 40% sulfuric acid.
In a certain scheme, in the step (2), the sodium nitrite is an aqueous solution of sodium nitrite, and the concentration of the aqueous solution of sodium nitrite is 5-45%, preferably 20-30%.
In one embodiment, in step (2), the molar ratio of the compound of formula II to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), e.g. 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6.
In one embodiment, in step (2), the acid is added in an amount of 2 to 10ml/kg, preferably 2 to 5ml/kg, more preferably 3 to 4ml/kg, relative to the compound of formula II.
In one embodiment, in step (2), the hydrolysis is carried out at a temperature of 80 to 140 ℃, preferably 100 to 130 ℃, for example 120 ℃.
In one embodiment, in the step (2), the time for the hydrolysis is 2 to 10 hours, preferably 5 to 6 hours.
In a certain scheme, in the step (2), the preparation method further comprises the following steps: stirring, cooling, and suction filtering to obtain the compound of formula I.
In a certain scheme, in the step (2), the preparation method comprises the following steps: the compound of formula II is hydrolyzed in the presence of 40% sulfuric acid and 20% aqueous sodium nitrite to give the compound of formula I at a temperature of 120 ℃.
In one embodiment, in the step (1), the concentration of the sulfuric acid is 80 to 85%, preferably 80%.
In one embodiment, in step (1), the molar ratio of the compound of formula III to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), e.g. 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6.
In one embodiment, in step (1), the amount of sulfuric acid added is 2 to 10ml/kg, preferably 4 to 6ml/kg, for example 5ml/kg, relative to the compound of formula III.
In one embodiment, in step (1), the hydrolysis time is 1 to 8 hours, preferably 3 hours.
In one embodiment, in step (1), the hydrolysis temperature is 140 to 150 ℃, preferably 140 ℃.
In one embodiment, in step (1), the preparation method comprises the following steps: in the absence of organic solvents, the compounds of formula III are hydrolysed in the presence of 80% sulfuric acid at a temperature of 140 ℃.
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 reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that: the preparation method provided by the invention provides a novel method for synthesizing o-trifluoromethyl benzoic acid, and has high yield and purity and convenient operation; meanwhile, no organic solvent is needed, and the method is more in line with green chemistry.
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.
Purity (content) analysis method:
GC analysis parameters:
example 1
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, namely preparing an 80% sulfuric acid solution, placing the solution into a flask, adding raw materials according to a feeding ratio, heating to 140 ℃, reacting for 3 hours, performing central control, wherein after the raw materials react, the content of an intermediate o-trifluoromethyl benzamide is 97%, preparing a 20% sodium nitrite aqueous solution, cooling to room temperature, dropwise adding the sodium nitrite solution, after the dropwise adding, performing heat preservation, performing central control (120-140 ℃ for heat preservation) for 5 hours, and performing stirring, cooling and suction filtration to obtain 92g of a product with the purity: 99% (GC), yield 82%.
1 H NMR(400MHz,DMSO-d6)8.19(d,J＝7.8Hz,1H),8.13(s,1H),7.96(d,J＝7.7Hz,1H),7.72(t,J＝7.8Hz,1H)
Example 2
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, namely preparing an 80% sulfuric acid solution, placing the solution into a flask, adding raw materials according to a feeding ratio, heating to 140 ℃, reacting for 3 hours, performing central control, wherein after the raw materials are reacted, the content of an intermediate o-trifluoromethyl benzamide is 96.4%, preparing a 20% sodium nitrite aqueous solution, cooling to 120 ℃, dropwise adding the sodium nitrite solution, performing heat preservation, performing central control to 5 hours, stirring, cooling and suction filtering to obtain a product with the purity of 90 g: 96.4% (GC), yield 81%.
Example 3
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, preparing 80% sulfuric acid solution, placing the solution into a flask, adding raw materials according to a feeding ratio, heating to 140 ℃, reacting for 3 hours, performing central control, after the raw materials react, preparing 20% sodium nitrite aqueous solution with the content of the intermediate o-trifluoromethyl benzamide of 97.3%, cooling to 120 ℃, dropwise adding sodium nitrite solution, after dropwise adding, performing heat preservation, performing central control to 5 hours, performing product content of 98.2%, stirring, cooling, and performing suction filtration to obtain 84g of a product with the purity: 97.3% (GC) yield 75%.
Example 4
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, preparing an 80% sulfuric acid solution, placing the solution into a flask, adding raw materials according to a feeding ratio, heating to 140 ℃, reacting for 3 hours, performing central control, and performing post treatment after the raw materials are reacted to obtain the intermediate o-trifluoromethyl benzamide with the content of 97.2%.105.2g, purity: 97.2% (GC) yield 95.1%.
1H NMR(600MHz,DMSO-d6)δ7.92(s,1H),7.73(d,J＝7.8Hz,1H),7.67(t,J＝7.5Hz,1H),7.59(dd,J＝13.9,5.9Hz,2H),7.51(d,J＝7.6Hz,1H).
Example 5
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, preparing a 40% sulfuric acid solution, placing the solution into a flask, adding the raw materials prepared in the example 4 according to a feeding ratio, heating to 120 ℃, preparing a 20% sodium nitrite aqueous solution, dropwise adding the sodium nitrite solution, after the dropwise adding, keeping the temperature for controlling to 6 hours, stirring and cooling the solution until the product content is 98%, and performing suction filtration to obtain 132g of a product with the purity: 98% (GC), yield 87%.
Example 6
The reaction equation is:
experimental feed table:
experimental operation:
preparing an experiment, preparing a 40% sulfuric acid solution, placing the solution into a flask, adding the raw materials prepared in the example 4 at room temperature according to a feeding ratio, preparing a 20% sodium nitrite aqueous solution, dropwise adding the sodium nitrite solution at room temperature, heating to 120 ℃ after the dropwise adding is finished, performing heat preservation, controlling the temperature to 6h, stirring, cooling and suction filtering to obtain 129g of a product with the purity: 98% (GC) yield 84.8%.
The above-described embodiments are merely preferred embodiments of the present invention, and are not intended to limit the present invention in any way. While the invention has been described with reference to preferred embodiments, it is not intended to be limiting. Therefore, any simple modification, equivalent variation and modification of the above embodiments according to the technical substance of the present invention shall fall within the scope of the technical solution of the present invention.
Claims (10)
1. A process for the preparation of a compound of formula I comprising the steps of:
(1) Hydrolyzing a compound of formula III in the presence of sulfuric acid in the absence of an organic solvent;
(2) The reaction liquid obtained in the step (1) reacts in the presence of sodium nitrite to obtain the compound shown in the formula I,
the concentration of the sulfuric acid is 75-90%;
the reaction temperature in the step (1) is 100-150 ℃;
the reaction temperature in the step (2) is 80-140 ℃.
2. A process for the preparation of a compound of formula I according to claim 1, wherein the process meets one or more of the following conditions:
(1) The concentration of the sulfuric acid is 80-85%;
(2) The sodium nitrite is sodium nitrite aqueous solution, and the concentration of the sodium nitrite aqueous solution is preferably 5-45%;
(3) The mol ratio of the compound of the formula III to sodium sulfite is 1 (1-2);
(4) The feeding amount of the sulfuric acid relative to the compound of the formula III is 2-10 ml/kg;
(5) The reaction time in the step (1) is 1 to 8 hours;
(6) The reaction time in the step (2) is 2-10 hours;
(7) The reaction temperature in the step (1) is 140-150 ℃; and
(8) The reaction temperature in the step (2) is 120-140 ℃.
3. A process for the preparation of a compound of formula I according to claim 2, wherein the process meets one or more of the following conditions:
(1) The concentration of sulfuric acid is 80%;
(2) The concentration of the sodium nitrite aqueous solution is 20-30%;
(3) The mol ratio of the compound of the formula III to sodium sulfite is 1 (1.1-1.6);
(4) The addition amount of the sulfuric acid relative to the compound of the formula III is 4-6ml/kg;
(5) The reaction time in step (1) was 3 hours;
(6) The reaction time in the step (2) is 5-6 hours;
(7) The reaction temperature in the step (1) is 140 ℃; and
(8) The reaction temperature in step (2) was 120 ℃.
4. A process for the preparation of a compound of formula I according to claim 2, wherein the process meets one or more of the following conditions:
(1) The concentration of the sodium nitrite aqueous solution is 20%;
(2) The molar ratio of the compound of formula III to sodium sulfite is 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6; and
(3) The amount of sulfuric acid added was 5ml/kg relative to the compound of formula III.
5. A process for the preparation of a compound of formula I according to any one of claims 1 to 4, comprising the steps of:
(1) In the absence of an organic solvent, hydrolyzing the compound of formula III in the presence of 80% sulfuric acid at 140 ℃;
(2) The reaction liquid obtained in the step (1) reacts with 20% sodium nitrite to obtain the compound shown in the formula I, and the reaction temperature is 120 ℃.
6. A process for the preparation of a compound of formula II comprising the steps of: hydrolyzing the compound of the formula III in the presence of sulfuric acid under the condition of no organic solvent to obtain the compound of the formula II,
the concentration of the sulfuric acid is 75-90%;
the temperature of the hydrolysis is 100-150 ℃.
7. A process for the preparation of a compound of formula II according to claim 6, wherein the process meets one or more of the following conditions:
(1) The concentration of the sulfuric acid is 80-85%, preferably 80%;
(2) The molar ratio of the compound of formula III to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), for example 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6;
(3) The sulfuric acid is added in an amount of 2 to 10ml/kg, preferably 4 to 6ml/kg, for example 5ml/kg, relative to the compound of formula III;
(4) The hydrolysis time is 1 to 8 hours, preferably 3 hours; and
(5) The temperature of the hydrolysis is 140 to 150 ℃, preferably 140 ℃.
8. A process for the preparation of a compound of formula I, comprising the steps of:
(1) Hydrolyzing the compound of the formula III in the presence of sulfuric acid in the absence of an organic solvent to obtain a compound of the formula II,
the concentration of the sulfuric acid is 75-90%;
the temperature of the hydrolysis is 100-150 ℃;
(2) Hydrolyzing the compound of the formula II in the presence of acid and sodium nitrite to obtain a compound of the formula I,
the acid is sulfuric acid or hydrochloric acid;
the concentration of sulfuric acid is 20-80% when the acid is sulfuric acid;
when the acid is hydrochloric acid, the concentration of the hydrochloric acid is 30-35%.
9. The process for the preparation of a compound of formula I according to claim 8, wherein step (2) fulfils one or more of the following conditions:
(1) In step (2), the acid is 30 to 50% sulfuric acid, for example 40% sulfuric acid;
(2) In the step (2), the sodium nitrite is sodium nitrite aqueous solution, and the concentration of the sodium nitrite aqueous solution is preferably 5-45%, and more preferably 20-30%;
(3) In step (2), the molar ratio of the compound of formula II to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), for example 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6;
(4) In step (2), the acid is added in an amount of 2 to 10ml/kg, preferably 2 to 5ml/kg, more preferably 3 to 4ml/kg, relative to the compound of formula II;
(5) In step (2), the temperature of the hydrolysis is 80 to 140 ℃, preferably 100 to 130 ℃, for example 120 ℃; and
(6) In the step (2), the hydrolysis time is 2 to 10 hours, preferably 5 to 6 hours;
and/or, the step (1) satisfies one or more of the following conditions:
(1) In the step (1), the concentration of the sulfuric acid is 80-85%, preferably 80%;
(2) In step (1), the molar ratio of the compound of formula III to sodium sulfite is 1 (1-2), preferably 1 (1.1-1.6), for example 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5 or 1:1.6;
(3) In step (1), the sulfuric acid is fed in an amount of 2 to 10ml/kg, preferably 4 to 6ml/kg, for example 5ml/kg, relative to the compound of formula III;
(4) In the step (1), the time of the hydrolysis is 1 to 8 hours, preferably 3 hours; and
(5) In step (1), the hydrolysis temperature is 140 to 150 ℃, preferably 140 ℃.
10. A process for the preparation of a compound of formula I according to claim 8 or 9, wherein in step (2) the preparation comprises the steps of: the compound of formula II is hydrolyzed in the presence of 40% sulfuric acid and 20% aqueous sodium nitrite to give the compound of formula I at a temperature of 120 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311505931.2A CN117623897A (en) | 2023-11-13 | 2023-11-13 | Preparation method of o-trifluoromethyl benzoic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311505931.2A CN117623897A (en) | 2023-11-13 | 2023-11-13 | Preparation method of o-trifluoromethyl benzoic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117623897A true CN117623897A (en) | 2024-03-01 |
Family
ID=90036854
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311505931.2A Pending CN117623897A (en) | 2023-11-13 | 2023-11-13 | Preparation method of o-trifluoromethyl benzoic acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117623897A (en) |
-
2023
- 2023-11-13 CN CN202311505931.2A patent/CN117623897A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6948419B2 (en) | New manufacturing method for chromanon derivatives | |
| CN116903499A (en) | Anhydrous fluorosulfonyl difluoro copper acetate salt, preparation method and application thereof | |
| CN117623897A (en) | Preparation method of o-trifluoromethyl benzoic acid | |
| CN114426517B (en) | Preparation method of 2-chloro-3-cyanopyridine | |
| CN108689874B (en) | Method for preparing 2-aryl malonamide and application thereof | |
| CN111302971B (en) | Method for continuously preparing 5-cyanodiol | |
| JP4169370B2 (en) | Process for producing acetophenones having a fluoroalkyl-substituted aromatic nucleus | |
| CN110229096B (en) | Preparation method of 2, 6-pyridinedicarboxylic acid | |
| JP4202148B2 (en) | Method for producing 2-aminotropone | |
| ZA200503239B (en) | Process for production of an acetylenic compound | |
| WO2019146508A1 (en) | Method for producing 2-chloroacetoacetamide | |
| CN103044332A (en) | Process for the preparation of n-substituted pyrazole compounds | |
| US7122676B2 (en) | Process for the preparation of 5,5′-bi-1H-tetrazolediammonium salts using hydrazine hydrate and dicyan as starting materials | |
| JPH0625111B2 (en) | Method for producing (trifluoromethyl) pyridine | |
| CN117430519A (en) | Preparation method of chlorohomoserine hydrochloride | |
| WO2019235493A1 (en) | Method for producing diaminobenzoic acid ester | |
| CN111499667A (en) | Method for synthesizing trivalent tetraarylferriporphyrin from pyrrole, aromatic aldehyde and ferrous salt | |
| JP3887757B2 (en) | Method for producing cyanobenzenesulfonyl chloride | |
| WO2023275677A1 (en) | A process for the preparation of 2-nitro-4-(methylsulfonyl)benzoic acid | |
| JP4371416B2 (en) | High purity 2,4-dichloro-3-alkyl-6-tert-butylphenol and process for producing the same | |
| JP3716581B2 (en) | Process for producing 4-fluoro-3-trifluoromethylphenol | |
| JP2010184904A (en) | Method for producing acetic acid compound | |
| JP2020083797A (en) | Method for producing aromatic halogen derivative | |
| CN111056993A (en) | Synthetic method of 3-chloromethylpyridine hydrochloride | |
| CN112898221A (en) | Preparation method and intermediate of benzoxazine diketone compound C |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |