CN112279790A - Preparation method of fomesafen original drug - Google Patents
Preparation method of fomesafen original drug Download PDFInfo
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- CN112279790A CN112279790A CN201910663494.4A CN201910663494A CN112279790A CN 112279790 A CN112279790 A CN 112279790A CN 201910663494 A CN201910663494 A CN 201910663494A CN 112279790 A CN112279790 A CN 112279790A
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- BGZZWXTVIYUUEY-UHFFFAOYSA-N fomesafen Chemical compound C1=C([N+]([O-])=O)C(C(=O)NS(=O)(=O)C)=CC(OC=2C(=CC(=CC=2)C(F)(F)F)Cl)=C1 BGZZWXTVIYUUEY-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 title description 3
- 229940079593 drug Drugs 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 40
- 238000009833 condensation Methods 0.000 claims abstract description 39
- 230000005494 condensation Effects 0.000 claims abstract description 39
- 150000001875 compounds Chemical class 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 32
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 24
- 238000006396 nitration reaction Methods 0.000 claims abstract description 22
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000005576 amination reaction Methods 0.000 claims abstract description 16
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 11
- 230000020477 pH reduction Effects 0.000 claims abstract description 10
- 238000006482 condensation reaction Methods 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 31
- 239000007795 chemical reaction product Substances 0.000 claims description 20
- DNUYOWCKBJFOGS-UHFFFAOYSA-N 2-[[10-(2,2-dicarboxyethyl)anthracen-9-yl]methyl]propanedioic acid Chemical compound C1=CC=C2C(CC(C(=O)O)C(O)=O)=C(C=CC=C3)C3=C(CC(C(O)=O)C(O)=O)C2=C1 DNUYOWCKBJFOGS-UHFFFAOYSA-N 0.000 claims description 17
- IJFXRHURBJZNAO-UHFFFAOYSA-N meta--hydroxybenzoic acid Natural products OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 claims description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000000126 substance Substances 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- 239000000047 product Substances 0.000 claims description 12
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 239000004557 technical material Substances 0.000 claims description 9
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 8
- 159000000000 sodium salts Chemical group 0.000 claims description 8
- 239000002699 waste material Substances 0.000 claims description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- XILPLWOGHPSJBK-UHFFFAOYSA-N 1,2-dichloro-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Cl)C(Cl)=C1 XILPLWOGHPSJBK-UHFFFAOYSA-N 0.000 claims description 5
- 229910002651 NO3 Inorganic materials 0.000 claims description 4
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 4
- 238000007599 discharging Methods 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 4
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
- 229910017604 nitric acid Inorganic materials 0.000 claims description 4
- 150000004767 nitrides Chemical class 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 238000003860 storage Methods 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 229910003844 NSO2 Inorganic materials 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000005086 pumping Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 6
- 239000010865 sewage Substances 0.000 abstract description 4
- 238000003915 air pollution Methods 0.000 abstract description 3
- 239000000376 reactant Substances 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000005457 optimization Methods 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
-
- 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
- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of fomesafen technical, in particular to a preparation method of fomesafen technical, which comprises three major parts of a production process of the fomesafen technical: condensation, nitration and amination, wherein the condensation manufacturing process is divided into three steps, namely salification, condensation and acidification, the alkaline effect in the condensation reaction process can be controlled by slightly increasing the input amount of a reactant sodium hydroxide, and the cost of sewage treatment can be reduced while the effect of the original process can be achieved; dissolving a condensation compound in an acidification kettle by using a solvent dichloroethane after a condensation process technology, and introducing the solution of the condensation compound into a nitration process by using a pump; after the nitration process is finished, the nitrated compound is dissolved in a nitration reaction kettle by using a solvent chlorobenzene, and the nitrated compound is led to an amination process by using a pump, so that the closed production is realized, the air pollution is prevented, and meanwhile, the consumption of raw materials can be reduced in the production process.
Description
Technical Field
The invention relates to a preparation method of fomesafen technical, in particular to a preparation method of fomesafen technical.
Background
In the prior art, the production of fomesafen is divided into three parts: condensation, nitration and amination, and in the prior art, m-hydroxybenzoic acid, sodium hydroxide, potassium carbonate, 3, 4-dichlorotrifluorotoluene and the like are added during the condensation reaction; the potassium carbonate does not participate in the reaction, is only used for controlling the condensation reaction process to keep alkalinity so as to be beneficial to smooth reaction, and has larger input amount, the use amount of hydrochloric acid can be increased in the later acidification reaction process, the generated salt is dissolved in the wastewater, and the cost of sewage treatment is increased.
In the prior art, a centrifuge is needed to remove a large amount of water after the condensation process is finished; after the nitration procedure is finished, filtering out the nitrated compound by using a suction filtration tank; the two operation modes belong to open-air operation and bring great air pollution.
Disclosure of Invention
The invention aims to provide a preparation method of fomesafen technical, which can control the alkaline effect in the condensation reaction process by slightly increasing the input amount of reactant sodium hydroxide, and can reduce the cost of sewage treatment while still achieving the effect of the original process.
The purpose of the invention is realized by the following technical scheme:
a preparation method of fomesafen technical comprises three major parts of the production process of the fomesafen technical: condensation, nitration and amination, wherein the preparation process of the condensation comprises three steps, namely salt formation, condensation and acidification, and is characterized in that: the method comprises the following steps:
the method comprises the following steps: salifying: reacting m-hydroxybenzoic acid and sodium hydroxide for 2 hours under normal pressure in a system taking water as a solvent, controlling the reaction temperature at 90-100 ℃, wherein the reaction products are disodium salt of the m-hydroxybenzoic acid and water, and the pH value at the end point of the reaction is about 10;
step two: condensation: reacting the dehydrated disodium salt of m-hydroxybenzoic acid, 3, 4-dichlorotrifluorotoluene and potassium carbonate in an anhydrous dimethyl sulfoxide system for 6 hours under normal pressure, controlling the reaction temperature at 160-170 ℃, and controlling the reaction end point to be that the ratio of the product to the m-hydroxybenzoic acid is more than 20: 1, passing; the reaction product is sodium salt and sodium chloride of condensation compound, the reaction product is dissolved by adding water after removing solvent dimethyl sulfoxide;
step three: acidifying: reacting sodium salt of a condensation compound with hydrochloric acid for half an hour at normal temperature and normal pressure under stirring in a system taking water as a solvent, wherein reaction products are the condensation compound and sodium chloride, the condensation compound is dissolved by dichloroethane and enters a nitration procedure, and the sodium chloride enters a water layer to be discharged;
step four: nitration: and (3) dehydrating the condensate solution, reacting the dehydrated condensate solution with mixed acid of concentrated nitric acid and concentrated sulfuric acid in a dichloroethane system for 2 hours at normal pressure in the presence of acetic anhydride, wherein the reaction end point is that the amount of the nitride and the condensate is more than 20: 1, passing; after the reaction is qualified, adding water to stop the reaction, and then standing for layering; dissolving the product nitrate in a dichloroethane layer, and discharging a waste acid layer to a waste acid storage tank; the solvent layer is washed by water, removed of solvent and the like to obtain a nitrated compound; dissolving the nitrated compound with chlorobenzene, and pumping into an amination process;
step five: amination: reacting the nitrated compound with methylsulfonamide in the presence of phosphorus oxychloride in a system with chlorobenzene as a solvent for 7 hours under normal pressure to obtain a reaction product of fomesafen, phosphate and hydrogen chloride; after the reaction is finished, the solvent is removed, and the product fomesafen is obtained after the processes of water washing, drying and the like.
As a further optimization of the technical scheme, the preparation method of fomesafen technical material of the invention comprises the following chemical formula of salt forming reaction:
HO(C6H4)COOH+2NaOH---NaO(C6H4)COONa+2H2O。
as further optimization of the technical scheme, the preparation method of fomesafen technical material of the invention comprises the following chemical formula of condensation reaction:
NaO(C6H4)COONa+F3C(C6H3)CL2---F3C(C6H3CL)O(C6H4)COONa+NaCL。
as further optimization of the technical scheme, the preparation method of fomesafen technical material of the invention comprises the following chemical equation of the acidification reaction:
F3C(C6H3CL)O(C6H4)COONa+HCL---F3C(C6H3CL)O(C6H4)COOH+NaCL。
as further optimization of the technical scheme, the invention discloses a preparation method of fomesafen technical, which comprises the following steps
As further optimization of the technical scheme, the invention provides a preparation method of fomesafen technical, and the chemical equation of the nitration reaction is as follows:
F3C(C6H3CL)O(C6H4)COOH+HNO3---F3C(C6H3CL)O(C6H4NO2)COOH+H2O。
as further optimization of the technical scheme, the preparation method of fomesafen technical material of the invention comprises the following chemical formula:
F3C(C6H3CL)O(C6H4NO2)COOH+H2NSO2CH3+POCL3---F3C(C6H3CL)O(C6H4NO2)CO HNSO2CH3 +H3PO4+HCL。
the preparation method of the fomesafen technical has the beneficial effects that:
the preparation method of the fomesafen original drug can control the alkaline effect of the condensation reaction process by slightly increasing the input amount of the reactant sodium hydroxide, and can reduce the cost of sewage treatment while still achieving the effect of the original process; dissolving a condensation compound in an acidification kettle by using a solvent dichloroethane after a condensation process technology, and introducing the solution of the condensation compound into a nitration process by using a pump; after the nitration process is finished, the nitrated compound is dissolved in a nitration reaction kettle by using a solvent chlorobenzene, and the nitrated compound is led to an amination process by using a pump, so that the closed production is realized, the air pollution is prevented, and meanwhile, the consumption of raw materials can be reduced in the production process.
Detailed Description
The present invention is described in further detail below.
The first embodiment is as follows:
a preparation method of fomesafen technical comprises three major parts of the production process of the fomesafen technical: condensation, nitration and amination, the manufacturing process of the condensation being divided into three steps, salt formation, condensation and acidification, the method comprising the steps of:
the method comprises the following steps: salifying: reacting m-hydroxybenzoic acid and sodium hydroxide for 2 hours under normal pressure in a system taking water as a solvent, controlling the reaction temperature at 90-100 ℃, wherein the reaction products are disodium salt of the m-hydroxybenzoic acid and water, and the pH value at the end point of the reaction is about 10;
step two: condensation: reacting the dehydrated disodium salt of m-hydroxybenzoic acid, 3, 4-dichlorotrifluorotoluene and potassium carbonate in an anhydrous dimethyl sulfoxide system for 6 hours under normal pressure, controlling the reaction temperature at 160-170 ℃, and controlling the reaction end point to be that the ratio of the product to the m-hydroxybenzoic acid is more than 20: 1, passing; the reaction product is sodium salt and sodium chloride of condensation compound, the reaction product is dissolved by adding water after removing solvent dimethyl sulfoxide;
step three: acidifying: reacting sodium salt of a condensation compound with hydrochloric acid for half an hour at normal temperature and normal pressure under stirring in a system taking water as a solvent, wherein reaction products are the condensation compound and sodium chloride, the condensation compound is dissolved by dichloroethane and enters a nitration procedure, and the sodium chloride enters a water layer to be discharged;
step four: nitration: and (3) dehydrating the condensate solution, reacting the dehydrated condensate solution with mixed acid of concentrated nitric acid and concentrated sulfuric acid in a dichloroethane system for 2 hours at normal pressure in the presence of acetic anhydride, wherein the reaction end point is that the amount of the nitride and the condensate is more than 20: 1, passing; after the reaction is qualified, adding water to stop the reaction, and then standing for layering; dissolving the product nitrate in a dichloroethane layer, and discharging a waste acid layer to a waste acid storage tank; the solvent layer is washed by water, removed of solvent and the like to obtain a nitrated compound; dissolving the nitrated compound with chlorobenzene, and pumping into an amination process;
step five: amination: reacting the nitrated compound with methylsulfonamide in the presence of phosphorus oxychloride in a system with chlorobenzene as a solvent for 7 hours under normal pressure to obtain a reaction product of fomesafen, phosphate and hydrogen chloride; after the reaction is finished, the solvent is removed, and the product fomesafen is obtained after the processes of water washing, drying and the like.
The second embodiment is as follows:
in this embodiment, the first embodiment is further explained, and the chemical equation of the salt-forming reaction is:
HO(C6H4)COOH+2NaOH---NaO(C6H4)COONa+2H2o; 425kg of m-hydroxybenzoic acid and 246kg of sodium hydroxide are reacted for 2 hours under normal pressure in a system taking 250kg of water as a solvent; the reaction temperature is controlled at 90-100 ℃; adding materials according to an equal molar ratio; the reaction product is disodium salt of m-hydroxybenzoic acid and water; the pH at the end of the reaction was about 10.
The third concrete implementation mode:
in this embodiment, the first embodiment is further explained, and the chemical equation of the condensation reaction is:
NaO(C6H4)COONa+F3C(C6H3)CL2---F3C(C6H3CL)O(C6H4) COONa + NaCL; reacting the dehydrated disodium salt of m-hydroxybenzoic acid with 638kg of 3, 4-dichlorobenzotrifluoride and potassium carbonate in 1200kg of anhydrous dimethyl sulfoxide system for 6 hours at normal pressure; the reaction temperature is controlled at 160-170 ℃; the reaction end point is that the ratio of the product to the m-hydroxybenzoic acid is more than 20: 1, passing; the reaction products are sodium salt and sodium chloride of a condensation compound; after the reaction product is removed of the solvent dimethyl sulfoxide, 1500kg of water is added for dissolving.
The fourth concrete implementation mode:
in this embodiment, the first embodiment is further explained, and the chemical equation of the acidification reaction is:
F3C(C6H3CL)O(C6H4)COONa+HCL---F3C(C6H3CL)O(C6H4) COOH + NaCL; reacting the sodium salt of the condensation compound with 600kg of hydrochloric acid in a system taking 4000kg of water as a solvent for half an hour at normal temperature and normal pressure under stirring; the reaction products are condensation compound and sodium chloride; the condensation compound is dissolved by dichloroethane and enters the nitration procedure, and the sodium chloride enters the water layer and is discharged.
The fifth concrete implementation mode:
in this embodiment, the first embodiment is further explained, and the chemical equation of the nitration reaction is:
F3C(C6H3CL)O(C6H4)COONa+HCL---F3C(C6H3CL)O(C6H4) COOH + NaCL; and (3) dehydrating the condensate solution, and reacting the dehydrated condensate solution with mixed acid of 480kg of concentrated nitric acid 1150kg of concentrated sulfuric acid in the presence of acetic anhydride for 2 hours at normal pressure in a dichloroethane system, wherein the reaction end point is that the amount of the nitride and the condensate is more than 20: 1, passing; after the reaction was passed, 200kg of water was added to terminate the reaction, followed by standing and separation. Dissolving the product nitrate in a dichloroethane layer, and discharging a waste acid layer to a waste acid storage tank; the solvent layer is washed by water, removed of solvent and the like to obtain a nitrated compound; the nitrated compound is packaged and then transferred to an amination procedure.
The sixth specific implementation mode:
in this embodiment, the chemical equation of the amination reaction is as follows:
F3C(C6H3CL)O(C6H4NO2)COOH+H2NSO2CH3+POCL3---F3C(C6H3CL)O(C6H4NO2)CO HNSO2CH3 +H3PO4+ HCL; reacting the nitrated compound with methylsulfonamide in the presence of phosphorus oxychloride in a system with chlorobenzene as a solvent for 7 hours under normal pressure to obtain a reaction product of fomesafen, phosphate and hydrogen chloride; after the reaction is finished, the solvent is removed, and the product fomesafen is obtained after the processes of water washing, drying and the like.
It is to be understood that the above description is not intended to limit the present invention, and the present invention is not limited to the above examples, and that various changes, modifications, additions and substitutions which are within the spirit and scope of the present invention and which may be made by those skilled in the art are also within the scope of the present invention.
Claims (6)
1. A preparation method of fomesafen technical comprises three major parts of the production process of the fomesafen technical: condensation, nitration and amination, wherein the preparation process of the condensation comprises three steps, namely salt formation, condensation and acidification, and is characterized in that: the method comprises the following steps:
the method comprises the following steps: salifying: reacting m-hydroxybenzoic acid and sodium hydroxide for 2 hours under normal pressure in a system taking water as a solvent, controlling the reaction temperature at 90-100 ℃, wherein the reaction products are disodium salt of the m-hydroxybenzoic acid and water, and the pH value at the end point of the reaction is about 10;
step two: condensation: reacting the dehydrated disodium salt of m-hydroxybenzoic acid, 3, 4-dichlorotrifluorotoluene and potassium carbonate in an anhydrous dimethyl sulfoxide system for 6 hours under normal pressure, controlling the reaction temperature at 160-170 ℃, and controlling the reaction end point to be that the ratio of the product to the m-hydroxybenzoic acid is more than 20: 1, passing; the reaction product is sodium salt and sodium chloride of condensation compound, the reaction product is dissolved by adding water after removing solvent dimethyl sulfoxide;
step three: acidifying: reacting sodium salt of a condensation compound with hydrochloric acid for half an hour at normal temperature and normal pressure under stirring in a system taking water as a solvent, wherein reaction products are the condensation compound and sodium chloride, the condensation compound is dissolved by dichloroethane and enters a nitration procedure, and the sodium chloride enters a water layer to be discharged;
step four: nitration: and (3) dehydrating the condensate solution, reacting the dehydrated condensate solution with mixed acid of concentrated nitric acid and concentrated sulfuric acid in a dichloroethane system for 2 hours at normal pressure in the presence of acetic anhydride, wherein the reaction end point is that the amount of the nitride and the condensate is more than 20: 1, passing; after the reaction is qualified, adding water to stop the reaction, and then standing for layering; dissolving the product nitrate in a dichloroethane layer, and discharging a waste acid layer to a waste acid storage tank; the solvent layer is washed by water, removed of solvent and the like to obtain a nitrated compound; dissolving the nitrated compound with chlorobenzene, and pumping into an amination process;
step five: amination: reacting the nitrated compound with methylsulfonamide in the presence of phosphorus oxychloride in a system with chlorobenzene as a solvent for 7 hours under normal pressure to obtain a reaction product of fomesafen, phosphate and hydrogen chloride; after the reaction is finished, the solvent is removed, and the product fomesafen is obtained after the processes of water washing, drying and the like.
2. The method for preparing fomesafen technical material according to claim 1, which is characterized in that: the chemical equation of the salt forming reaction is as follows:
HO(C6H4)COOH+2NaOH---NaO(C6H4)COONa+2H2O。
3. the method for preparing fomesafen technical material according to claim 1, which is characterized in that: the chemical equation of the condensation reaction is as follows:
NaO(C6H4)COONa+F3C(C6H3)CL2---F3C(C6H3CL)O(C6H4)COONa+NaCL。
4. the method for preparing fomesafen technical material according to claim 1, which is characterized in that: the chemical equation of the acidification reaction is as follows:
F3C(C6H3CL)O(C6H4)COONa+HCL---F3C(C6H3CL)O(C6H4)COOH+NaCL。
5. the method for preparing fomesafen technical material according to claim 1, which is characterized in that: the chemical equation of the nitration reaction is as follows:
F3C(C6H3CL)O(C6H4)COOH+HNO3---F3C(C6H3CL)O(C6H4NO2)COOH+H2O。
6. the method for preparing fomesafen technical material according to claim 1, which is characterized in that: the chemical equation of the amination reaction is as follows:
F3C(C6H3CL)O(C6H4NO2)COOH+H2NSO2CH3+POCL3---F3C(C6H3CL)O(C6H4NO2)CO HNSO2CH3 +H3PO4+HCL。
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Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4313000A (en) * | 1981-04-02 | 1982-01-26 | Ici Americas Inc. | Process for preparing 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitro-N-alkanesulphonyl benzamides from a toluene derivative and intermediates |
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| CN107032979A (en) * | 2017-06-12 | 2017-08-11 | 青岛瀚生生物科技股份有限公司 | The preparation method of 3 (trifluoromethyl of 2 chlorine 4) phenoxy benzoic acids |
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