CN107298653A - A kind of method for synthesizing 4 trifluoromethyl nicotinic acids - Google Patents
A kind of method for synthesizing 4 trifluoromethyl nicotinic acids Download PDFInfo
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- CN107298653A CN107298653A CN201710647962.XA CN201710647962A CN107298653A CN 107298653 A CN107298653 A CN 107298653A CN 201710647962 A CN201710647962 A CN 201710647962A CN 107298653 A CN107298653 A CN 107298653A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
Abstract
The present invention relates to a kind of method for synthesizing 4 trifluoromethyl nicotinic acids, specifically related to a kind of method for the trifluoromethyl nicotinic acid of key intermediate 4 for synthesizing flonicamid, this method is with 1,1, the aminobutene ketone of 1 trifluoro 4 and 2 methoxymethylene dimethyl malenates are raw material, first step reaction：The aminobutene ketone of 1,1,1 trifluoro 4 and 2 methoxymethylene dimethyl malenates react under the alkalescence condition of polar solvent, obtain first step reaction system；Second step reacts：Alcohols solvent is added in first step reaction system and carries out heating response, second step reaction system is obtained；Three-step reaction：Acid solution is added in second step reaction system to be reacted, and obtains 4 trifluoromethyl nicotinic acids.The inventive method raw material is easy to get, easy to operate, and cost is low, and side reaction is few, and product purity is high, suitable industrialized production.
Description
Technical field
The invention belongs to the key intermediate 4- trifluoros in pesticide intermediate synthesis field, more particularly to a kind of flonicamid
The synthetic method of methylnicotinic acid.
Background technology
Flonicamid is nicotinamide insecticide, to various suckings pest effectively, and with good infiltration
Effect, can from plant root to stem, leaf portion infiltration.The medicament causes effect by hindering insect act of sucking, insect intake medicine
Stop sucking quickly after agent, it is last hungry and dead.The medicament can make the lancet tissue of the sucking property insect such as aphid can not insert plant
Thing tissue and cause effect.All there is insecticidal activity to the adult and larva of aphid.Its mechanism of action is novel, and presently commercially available other
Insecticide no interactions resistance, to honeybee low toxicity.Flonicamid is divided into by international resistance to insecticides Action Committee (IRAC)
9C classes, selective Homoptera anti-feedant.
4- trifluoromethyl nicotinic acids are the N-1 step key intermediates for synthesizing flonicamid, and No. CAS is 158063-66-2, mesh
Preceding synthetic method disclosed in the prior art has a lot, such as China Patent No. for CN200910167945 patent report with
4,4,4- trifluoroacetic ethyl acetoacetates are cyclization under initiation material, with cyanoacetamide alkalescence condition, and POCl3 is by hydroxy chloride
In generation, then via palladium-catalyzed dose of dehalogenate, hydrolyzed under basic conditions obtains 4- trifluoromethyl nicotinic acids.Or obtaining the chloro- 3- cyanogen of 2,6-
After base -4- trifluoromethyl pyridines, first it is hydrolyzed, then catalytic eliminating halogen, obtain 4- trifluoromethyl nicotinic acids.The drawbacks of this method
It is to have used POCl3Raw material is done, toxicity is larger, heavy contamination, the wastewater flow rate of generation is larger, is unfavorable for industrialized production.
Further, European patent EP 0744400 and Japan Patent JP2007210923 reports, former by starting of ethyl vinyl ether
Material, is acylated with trifluoro-acetyl chloride/TFAA, 4- tri- is obtained through condensation, cyclization, hydrolysis under ammonolysis, alkalescence condition
Methyl fluoride nicotinic acid.The drawbacks of this method is to have used 3- methoxy-methyl acrylates or 3,3- dimethoxy methyl propionate to do original
Material, both raw material less stables are industrially not easy to obtain, and long import is expensive.
In patent US5360806, EP0580374 and Eur.J.Org.Chem.2003 is published in, 1569 Hes
Disclosed in Eur.J.Org.Chem.2003,1559 article with the iodo- 4- trifluoromethyl pyridines of 4- trifluoromethyl pyridines/3-, or
Chloro- 4- trifluoromethyl pyridines/2, the 6- dichlor-4-trifluoromethyl pyridines of person 2- are raw material, are reacted with highly basic under low temperature, the carbon of generation
Anion and carbon dioxide reaction, acidified, palladium chtalyst dehalogenate prepare 4- trifluoromethyl nicotinic acids.The drawbacks of this method is crucial
Step has used the highly basic such as n-BuLi, and needs to be reacted in a low temperature of -78 DEG C, as a consequence it is hardly possible to industrialize.
The drawbacks of present invention is solves current 4- trifluoromethyl nicotinic acids synthetic method, have developed a kind of new method, the party
Method not only solves above mentioned problem, and can improve the feasibility of commercial Application.
The content of the invention
The technical problems to be solved by the invention are to overcome above-mentioned weak point, a kind of synthesis fluorine pyridine worm of research and design
The method of the key intermediate 4- trifluoromethyl nicotinic acids of acid amides, this method does not use highly toxic substance, reaction condition gentle and raw material
It is easy to get, this method is regardless of what intermediate state material of leaving one's post, purity height, the steady quality of the 4- trifluoromethyl nicotinic acids of acquisition.
Specifically, the invention provides a kind of method of synthesis 4- trifluoromethyl nicotinic acids, it is characterised in that this method with 1,
1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxymethylenes dimethyl malenate is that raw material reaction prepares 4- trifluoromethyls
Any intermediate product is not isolated and purified in nicotinic acid, course of reaction.
2- methoxymethylenes dimethyl malenate is typically also referred to as methoxymethylene dimethyl malenate, No. CAS
For 22398-14-7, molecular formula is C7H10O5, molecular weight is 174.15.
Specifically, in the above method, methods described is with 1,1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxymethylenes third
Acid dimethyl is raw material, first step reaction：1,1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxymethylene malonic acid dimethyl
Ester reacts under the alkalescence condition of polar solvent, obtains first step reaction system；Second step reacts：In first step reaction system
Add alcohols solvent and carry out heating response, obtain second step reaction system；Three-step reaction：Added in second step reaction system
Acid solution is reacted, and obtains 4- trifluoromethyl nicotinic acids.
It is preferred that, any intermediate product is not isolated and purified in the above method, in course of reaction and refers to first step reaction completion
The intermediate product that end-product structural generation is participated in present in first step reaction system afterwards is not separated and purified, in the system
Proceed second step to react, end-product structural generation is participated in present in the second step reaction system after the completion of second step reaction
Intermediate product do not separate and purify, proceed three-step reaction in the system.
It is preferred that, in the above method, 1,1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxymethylene dimethyl malenate
Molar ratio be usually that equimolar ratio is reacted, it is preferred that 1,1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxyl groups is sub-
The molar ratio of methylmalonic acid dimethyl ester is 1: (0.8-1.2).
It is preferred that, in the above method, polar solvent is dimethyl sulfoxide, N, N- dimethyl formyls described in first step reaction
A kind of solvent or many of in amine, DMA, 1- methyl pyrrolidones, tetrahydrofuran or dioxane
Mixed solvent, the consumption of the solvent and the weight ratio of raw material are (2.0~40.0): 1, it is preferred that be (4.0~20.0): 1.
It is preferred that, in the above method, the alkalescence condition of polar solvent is by polar solvent described in first step reaction
Middle addition alkaline matter is obtained, and the alkaline matter is sodium methoxide, caustic alcohol, tert-butyl alcohol first, hydrofining, sodium hydride, hydroxide
One or more in potassium, diisopropylamine lithium, the consumption of the alkaline matter and 1,1,1- tri- fluoro- 4- aminobutenes ketone rubs
You are than being (1.0~1.5): 1, it is preferred that be (1.0~1.1): 1.
The first step reaction condition be：1,1,1- tri- fluoro- 4- aminobutenes ketone is dissolved in polar solvent, in -20~50
DEG C add alkaline matter, it is preferred that in -10~10 DEG C add alkaline matters, react 0.5~24 hour, it is preferred that reaction 1-2
Hour, 2- methoxymethylene dimethyl malenates are then added, are reacted 5-8 hours, first step reaction system is obtained.
It is preferred that, in the above method, in second step reaction, the alcohols solvent is methanol, ethanol, isopropanol, the tert-butyl alcohol
Or the one or more in isobutanol；The weight ratio of alcohols solvent consumption and raw material is (2.0~30.0): 1, it is preferred that be
(5.0~10.0): 1；Reaction temperature is the boiling point of the alcohols solvent, and heating reflux reaction 3-6 hours obtains second step reaction
System；
It is preferred that, in the above method, in three-step reaction, the acid solution is the solution of acidic materials, the acidity
Material is the one or more in sulfuric acid, hydrochloric acid, trifluoroacetic acid or formic acid, and the concentration of the acid solution middle acid substance is 3-
12mol/L, it is preferred that be 4-8mol/L.
It is preferred that, in the above method, the reaction temperature of three-step reaction is 50~100 DEG C, it is preferred that be 80-100 DEG C,
Reaction time is 1~10 hour, is subsequently cooled to room temperature, adjusts pH to 6-8, and filtration drying obtains 4- trifluoromethyl nicotinic acids.
The observation of 4- trifluoromethyl nicotinic acid courses of reaction and the adjustment of optimum reaction condition are obtained according to above-mentioned synthesis and divided
Analysis, present invention also offers a kind of method of synthesis 4- trifluoromethyl nicotinic acids, methods described has anti-as represented by following formula (A)
Process is answered, wherein first step reaction is addition reaction, and second step reaction is ring closure reaction, and three-step reaction is that hydrolysis decarboxylation is anti-
Should,
Structural formula I in the formula (A) is 1,1,1- tri- fluoro- 4- aminobutenes ketone, and formula II is 2- methoxyl group methylenes
Propylmalonic acid dimethyl ester, formula II I and structural formula IV are the intermediate state material that addition reaction is obtained, and structural formula V is that cyclization is anti-
The intermediate state material that should be obtained, structural formula VI is end-product 4- trifluoromethyl nicotinic acids.
First step reaction, second step reaction, the reaction condition of three-step reaction and above-mentioned reaction article in the formula (A)
Part content is identical.
Beneficial effects of the present invention：
1st, the 2- methoxymethylene dimethyl malenates used in the inventive method are easy to get, and can purchase this product, also may be used
It is condensed and is obtained with dimethyl malenate and trimethyl orthoformate, preparing 4- trifluoromethyl nicotinic acid ratios using it applies 3,3- bis-
Methoxy methyl propionate or 3- methoxy-methyl acrylates preparation 4- trifluoromethyl nicotinic acids are more efficient, and product purity is higher.
2nd, in the method for above-mentioned synthesis 4- trifluoromethyl nicotinic acids of the invention, course of reaction, which is added, adds acid solution
Step, wherein the decarboxylic reaction occurred is almost with hydrolysis cooperates with generation, does not increase unnecessary operating procedure additionally, also
It is that two concerted reactions are realized by single stepping.
3rd, each step safety simple to operate of above-mentioned synthesis 4- trifluoromethyl nicotinic acid methods of the invention, convenient post-treatment, if
It is standby to require low, it is adapted to industrialized production.
4th, in the above method of the invention, used 2- methoxymethylenes dimethyl malenate is cheap and easy to get, substitutes
Expensive 3- methoxy-methyl acrylates, reduce cost so that the feasibility of industrial production 4- trifluoromethyl nicotinic acids is higher.
Embodiment
The invention will be further described with reference to embodiments, but not limits the application of the present invention.
Raw material and reaction dissolvent, alkaline matter and acidic materials in example below are that market is commercially available.
Embodiment 1：
In 500ml flasks, 1- methyl pyrrolidone 100mL are added, 2.9 grams of sodium hydride is cooled to 0 DEG C, drop under stirring
Plus 1,1,1- tri- fluoro- 10 grams of 4- aminobutenes ketone, control temperature is below 10 DEG C, after reacting 1 hour, adds 2- methoxyl group methylenes
Propylmalonic acid dimethyl ester 12.5g, reacts 4 hours.Then methanol 200mL is added, 65 DEG C are heated to, after reacting 3 hours, added dense
300 grams of hydrochloric acid (30%wt), is heated to boiling, and back flow reaction 9 hours, distillation for removing methanol adds 300 grams of frozen water, filtered, filter
Cake is washed with water, and dries, obtains 6.8g yellow solids, yield 49%, the nuclear magnetic data of yellow solid is1HNMR (400MHz,
DMSO-d6)：D7.86 (d, J=5.2Hz, 1H), 8.97 (d, J=5.2Hz, 1H), 9.06 (s, 1H), 14.04 (bs, 1H), root
The purity that yellow solid is 4- trifluoromethyl nicotinic acids in 4- trifluoromethyl nicotinic acids, analysis detection yellow solid is determined according to nuclear magnetic data
For 98.7%,
Embodiment 2：
In 500ml flasks, DMF120mL is added, 12.4 grams of potassium tert-butoxide is cooled to 0 DEG C, is added dropwise 1,1,1- under stirring
Three fluoro- 12.8 grams of 4- aminobutenes ketone, control temperature is less than 10 DEG C, after reaction 1 hour, addition 2- methoxymethylenes the third two
Dimethyl phthalate 16.8g, reacts 3-5 hours.Then ethanol 250mL is added, 80 DEG C are heated to, after reacting 2-3 hours, dense salt is added
Ethanol is distilled off in 300 grams of acid, ebuillition of heated, back flow reaction 8-10 hours, adds 350 grams of frozen water, and filtering, filter cake is washed with water,
Dry, obtain 6.2g yellow solids, yield 35%, the nuclear magnetic data of yellow solid is1HNMR (400MHz, DMSO-d6)：
D7.86 (d, J=5.2Hz, 1H), 8.97 (d, J=5.2Hz, 1H), 9.06 (s, 1H), 14.04 (bs, 1H), according to nuclear magnetic data
Determine that the purity that yellow solid is 4- trifluoromethyl nicotinic acids in 4- trifluoromethyl nicotinic acids, analysis detection yellow solid is 99.1%,
Comparative example 1：
According to embodiment 1 and the method for embodiment 2,2- methoxymethylenes third are replaced with 3,3- dimethoxys methyl propionate
Acid dimethyl is reacted, and other conditions are identical, and the 4- trifluoromethyl nicotinic acid yields of acquisition are respectively 46% and 32%, and
The purity of the 4- trifluoromethyl nicotinic acids of acquisition is respectively 94.2% and 93.8%, and purity is less than 95%, higher if necessary to purity,
Other means of purification are needed to be purified again, industrial production increase purification step, power consumption increase.And 3,3- dimethoxy third
Sour methyl esters is domestic at present to be underproduced, quality is also unstable without volume production, so carrying out production 4- trifluoromethyls using the raw material
The industrialization of nicotinic acid is more difficult.
Comparative example 2：
According to embodiment 1 and the method for embodiment 2,2- methoxymethylenes the third two are replaced with 3- methoxy-methyl acrylates
Dimethyl phthalate, other conditions are identical, and the 4- trifluoromethyl nicotinic acid yields of acquisition are respectively 44% and 30%, and the 4- tri- obtained
The purity of methyl fluoride nicotinic acid is respectively 92.5% and 94.9%, and purity is less than 95%, higher, it is necessary to which other are pure if necessary to purity
Change means are purified again, industrial production increase purification step, power consumption increase.And the current state of 3- methoxy-methyl acrylates
Inside yield poorly, so the industrialization for produce 4- trifluoromethyl nicotinic acids using the raw material is difficult.
Claims (10)
1. a kind of method of synthesis 4- trifluoromethyl nicotinic acids, it is characterised in that methods described is with 1,1,1- tri- fluoro- 4- aminobutenes
Ketone and 2- methoxymethylenes dimethyl malenate be raw material reaction prepare in 4- trifluoromethyl nicotinic acids, course of reaction regardless of
From any intermediate product of purifying.
2. according to the method described in claim 1, it is characterised in that methods described is with 1,1,1- tri- fluoro- 4- aminobutenes ketone and 2-
Methoxymethylene dimethyl malenate is raw material, first step reaction：1,1,1- tri- fluoro- 4- aminobutenes ketone and 2- methoxyl groups is sub-
Methylmalonic acid dimethyl ester reacts under the alkalescence condition of polar solvent, obtains first step reaction system；Second step reacts：
Alcohols solvent is added in single step reaction system and carries out heating response, second step reaction system is obtained；Three-step reaction：In second step
Acid solution is added in reaction system to be reacted, and obtains 4- trifluoromethyl nicotinic acids.
3. method according to claim 2, it is characterised in that the polar solvent in the first step reaction is dimethyl sulfoxide,
It is a kind of molten in DMF, DMA, 1- methyl pyrrolidones, tetrahydrofuran or dioxane
Agent or many of mixed solvent, the consumption of the solvent and the weight ratio of raw material are (2.0~40.0): 1, it is preferably (4.0
~20.0): 1.
4. according to the method in claim 2 or 3, it is characterised in that the alkalescence of polar solvent described in the first step reaction
Condition be by polar solvent add alkaline matter obtain, the alkaline matter be sodium methoxide, caustic alcohol, potassium tert-butoxide,
One or more in hydrofining, sodium hydride, potassium hydroxide, diisopropylamine lithium, the consumption of the alkaline matter and 1,1,1-
The mol ratio of three fluoro- 4- aminobutenes ketone is (1.0~1.5): 1, be preferably (1.0~1.1): 1.
5. the method according to claim 3 or 4, it is characterised in that the condition of the first step reaction is：By 1,1,1- tri-
Fluoro- 4- aminobutenes ketone is dissolved in polar solvent, and alkaline matter is added in -20~50 DEG C, it is preferred that in -10~10 DEG C of additions
Alkaline matter, reacts 0.5~24 hour, it is preferred that reaction 1-2 hours, then adds 2- methoxymethylene malonic acid dimethyls
Ester, reacts 5-8 hours, obtains first step reaction system.
6. method according to claim 2, it is characterised in that in the second step reaction, the alcohols solvent be methanol,
One or more in ethanol, isopropanol, the tert-butyl alcohol or isobutanol；The weight ratio of alcohols solvent consumption and raw material for (2.0~
30.0): 1, it is preferred that be (5.0~10.0): 1；The temperature of second step reaction is the boiling point of the alcohols solvent, is heated to reflux
Reaction 3-6 hours, obtains second step reaction system；
7. method according to claim 2, it is characterised in that acid solution is acidic materials in the three-step reaction
Solution, the acidic materials are acidity in the one or more in sulfuric acid, hydrochloric acid, trifluoroacetic acid or formic acid, the acid solution
The concentration of material is 3-12mol/L, it is preferred that be 4-8mol/L.
8. method according to claim 2, it is characterised in that the reaction temperature of the three-step reaction is 50~100 DEG C,
It is preferred that, it is 80-100 DEG C, the reaction time is 1~10 hour, is subsequently cooled to room temperature, adjusts pH to 6-8, filtration drying, i.e.,
Obtain 4- trifluoromethyl nicotinic acids.
9. a kind of method of synthesis 4- trifluoromethyl nicotinic acids, methods described has the course of reaction as represented by following formula (A), wherein
First step reaction is addition reaction, and second step reaction is ring closure reaction, and three-step reaction reacts for hydrolysis decarboxylation,
Structural formula I in the formula (A) is 1,1,1- tri- fluoro- 4- aminobutenes ketone, and formula II is 2- methoxymethylenes third
Acid dimethyl, formula II I and structural formula IV are the intermediate state material that addition reaction is obtained, and structural formula V obtains for ring closure reaction
The intermediate state material arrived, structural formula VI is end-product 4- trifluoromethyl nicotinic acids.
10. method according to claim 9, it is characterised in that the first step reaction, second step reaction, three-step reaction
Reaction condition be the reaction condition described in claim 2-8.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574440A (en) * | 2020-05-25 | 2020-08-25 | 安徽金禾实业股份有限公司 | Preparation method of 4-trifluoromethyl nicotinic acid |
| CN113897238A (en) * | 2021-08-27 | 2022-01-07 | 安徽和欣润滑科技有限公司 | Lubricant with cooling function and processing technology thereof |
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|---|---|---|---|---|
| EP0744400A2 (en) * | 1995-05-26 | 1996-11-27 | Ishihara Sangyo Kaisha, Ltd. | Process for producing 4-trifluoromethylnicotinic acid |
| JP2004010572A (en) * | 2002-06-10 | 2004-01-15 | Ishihara Sangyo Kaisha Ltd | Method for producing 4-trifluoromethylnicotinic acid or its salt |
| JP2007210923A (en) * | 2006-02-08 | 2007-08-23 | Ishihara Sangyo Kaisha Ltd | Method for producing 4-trifluoromethylnicotinic acid or its salt |
| CN101851193A (en) * | 2009-10-20 | 2010-10-06 | 西华大学 | Preparation method of 4-trifluoromethyl nicotinic acid |
-
2017
- 2017-08-01 CN CN201710647962.XA patent/CN107298653B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0744400A2 (en) * | 1995-05-26 | 1996-11-27 | Ishihara Sangyo Kaisha, Ltd. | Process for producing 4-trifluoromethylnicotinic acid |
| JP2004010572A (en) * | 2002-06-10 | 2004-01-15 | Ishihara Sangyo Kaisha Ltd | Method for producing 4-trifluoromethylnicotinic acid or its salt |
| JP2007210923A (en) * | 2006-02-08 | 2007-08-23 | Ishihara Sangyo Kaisha Ltd | Method for producing 4-trifluoromethylnicotinic acid or its salt |
| CN101851193A (en) * | 2009-10-20 | 2010-10-06 | 西华大学 | Preparation method of 4-trifluoromethyl nicotinic acid |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111574440A (en) * | 2020-05-25 | 2020-08-25 | 安徽金禾实业股份有限公司 | Preparation method of 4-trifluoromethyl nicotinic acid |
| CN111574440B (en) * | 2020-05-25 | 2022-09-13 | 安徽金禾实业股份有限公司 | Preparation method of 4-trifluoromethyl nicotinic acid |
| CN113897238A (en) * | 2021-08-27 | 2022-01-07 | 安徽和欣润滑科技有限公司 | Lubricant with cooling function and processing technology thereof |
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