CN107721948A - A kind of preparation method of flufenacet - Google Patents
A kind of preparation method of flufenacet Download PDFInfo
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- CN107721948A CN107721948A CN201711137422.3A CN201711137422A CN107721948A CN 107721948 A CN107721948 A CN 107721948A CN 201711137422 A CN201711137422 A CN 201711137422A CN 107721948 A CN107721948 A CN 107721948A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/13—Oxygen atoms
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Abstract
The invention discloses a kind of preparation method of flufenacet, this method includes the trifluoromethyl 1 of 2 methylsulfonyl 5,3, the synthesis of 4 thiadiazoles, the synthesis of 2 hydroxyl N (4 fluoroaniline) N (1 Methylethyl) acetamide and [5 (the trifluoro glycosides) 1 of 4' fluorine N isopropyls 2, the imines of 3,4 thiadiazole 2] acetamide synthesis.The present invention screens the preparation method of optimal flufenacet by many experiments, whole technological design is reasonable, especially filter out optimal reaction condition, the steps such as the optimum amount ratios of reaction raw materials, reaction temperature, reaction time, reaction yield (up to more than 90%) can be greatly improved, side reaction can be reduced, improve reaction rate, realize that reaction raw materials recycle, significantly lower production cost, there is good application prospect.
Description
Technical field
The invention belongs to synthesising chemical technology field, and in particular to a kind of preparation method of flufenacet.
Background technology
Flufenacet, the fluoro- N- isopropyls -2- of Chinese 4- [thiadiazole -2- imines of 5- (trifluoro glycosides) -1,3,4-] acetyl
Amine, CAS registration numbers are 142459-58-3, and agricultural chemicals are a kind of.The combined coefficient of flufenacet is relatively low at present, and yield is low, and
Reaction condition requires high, and the feature of environmental protection is poor, and the flufenacet purity that synthesis obtains is relatively low, and cost is higher, industrially promotes difficulty
It is larger.
The content of the invention
Goal of the invention：The invention aims to overcome the deficiencies in the prior art, there is provided a kind of technological design is reasonable, operation
Convenient, especially combined coefficient is high, and yield is high, and discarded object is few, can be achieved to recycle, and cost is low, the high flufenacet of purity
Preparation method.
Technical scheme：In order to solve the above technical problems, the technical scheme that the present invention takes is：
A kind of preparation method of flufenacet, comprises the following steps：
Step (1)：2,2- methyl mercapto -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Trifluoroacetic acid is pumped into stand-by in trifluoroacetic acid measuring tank, it is cold that sulphur hydrazine, toluene stirring are then added in synthesis reactor
But to 10~20 DEG C, start that trifluoroacetic acid is added dropwise, 10~20 DEG C of temperature control during dropwise addition, completion of dropwise addition is stirred at room temperature
Reaction, after reaction terminates, then distill, after distillation terminates, obtain colourless liquid, i.e. 2,2- methyl mercapto -5- Trifluoromethyl-1s, 3,4-
Thiadiazoles；
Step (2)：2- methylsulfonyl -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Persulfate (preferably potassium peroxydisulfate, sodium peroxydisulfate etc.) is added in the reactor of step (1), is pumped into water, first
Alcohol, heating up 35~40 degree, be incubated 3~4 hours, take off methanol, cool to 25~30 degree, centrifugation obtains faint yellow flat crystal,
That is 2- methylsulfonyls -5- Trifluoromethyl-1s, 3,4- thiadiazoles；
Step (3)：The synthesis of N- isopropyl -4- fluoroanilines
By in 4- fluoronitrobenzenes, acetone, catalyst input autoclaves, 80 to 90 degree are warming up to, are passed through hydrogen, cool to
30 to 35 degree, filter to obtain catalyst, take organic phase point to remove moisture, obtain N- isopropyl -4- fluoroanilines；
Step (4)：2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
Will be stand-by in chloracetyl chloride suction chloracetyl chloride measuring tank, step (3) is then added in a kettle to be prepared
N- isopropyl -4- fluoroanilines, then vacuum be pumped into toluene mixing, chloracetyl chloride is added dropwise into reactor at room temperature, about 2 is small
When completion of dropwise addition, be warming up to 80~90 DEG C after completion of dropwise addition, and be incubated and terminate to reaction, the hydrogen chloride gas generated in reaction leads to
Cross tertiary effluent absorption and by-product hydrochloric acid be made, distilled after reaction and slough unreacted chloracetyl chloride and toluene mixture recycled,
After distillation terminates, cooling adds frozen water washing separation, and aqueous phase goes wastewater treatment, and organic phase adjusts PH with aqueous sodium carbonate, stands
Dividing goes aqueous phase to go wastewater treatment, obtains organic phase, as 2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide；
Step (5)：The synthesis of 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetyl that step (4) is prepared is added in a kettle
Amine, toluene, sodium acetate, frerrous chloride, it is warming up to 85~95 DEG C and is reacted, distilled after reaction, after distillation terminates, adds washing
Wash, stand to divide and go aqueous phase to go wastewater treatment, obtain organic phase, as 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls)
Acetamide；
Step (6)：The synthesis of 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) second that step (5) is prepared is added in synthesis reactor
Acid amides, ethanol, 60~70 DEG C of backflows are warming up to, is incubated to reaction and terminates, then distill at ambient pressure to 70~75 DEG C, slough second
Acetoacetic ester, sold as byproduct, 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) acetamide is produced after distillation；
Step (7)：The synthesis of flufenacet
2- hydroxy-ns-(4- fluoroanilines)-N- (1- methyl second that step (6) is prepared is pumped into reactor with vacuum
Base) acetamide, frerrous chloride/dichloroethanes, the 2- methylsulfonyl -5- Trifluoromethyl-1s that step (2) is prepared, 3,4- thiophenes two
Azoles, steam heating, reacts under the conditions of normal pressure, 65 to 75 DEG C, after reaction terminates, distills to 70 to 75 DEG C and sloughs the chloroethenes of 1,1- bis-
Alkane recycled, produced after distillation, ([thiadiazole -2- of 5- (trifluoro glycosides) -1,3,4- are sub- by the fluoro- N- isopropyls -2- of 4- for flufenacet
Amine] acetamide).
Preferably, the preparation method of described flufenacet, in step (1), mole of trifluoroacetic acid and sulphur hydrazine
Amount ratio is 3:1.
Preferably, the preparation method of described flufenacet, step (3)：By 4- fluoronitrobenzenes, acetone, catalysis
In agent input autoclave, 80 to 90 degree are warming up to, are passed through hydrogen, pressure maintains 0.6-0.7MPA until pressure is constant, cooling
To 30 degree, catalyst is filtered to obtain, takes organic phase point to remove moisture, obtains N- isopropyl -4- fluoroanilines；Wherein catalyst is thunder nickel, is urged
Agent dosage is 4- fluoronitrobenzene one thousandth moles.85 degree of the step reaction temperature.
Preferably, the preparation method of described flufenacet, step (4)：Chloracetyl chloride is pumped into chloracetyl chloride
It is stand-by in measuring tank, the N- isopropyl -4- fluoroanilines that step (3) is prepared then are added in a kettle, and then vacuum is taken out
Enter toluene mixing, chloracetyl chloride is added dropwise into reactor at room temperature, completion of dropwise addition in about 2 hours, 80 are warming up to after completion of dropwise addition
~90 DEG C, and be incubated and terminate to reaction, the hydrogen chloride gas generated in reaction is absorbed by tertiary effluent is made the hydrochloric acid of by-product 30%,
Unreacted chloracetyl chloride and toluene mixture recycled are sloughed in distillation after reaction, and after distillation terminates, cooling adds frozen water and washed
Separation is washed, aqueous phase goes wastewater treatment, and (tune can efficiently remove unnecessary acid to organic phase with aqueous sodium carbonate tune PH6 to 7
Matter), stand to divide and go aqueous phase to go wastewater treatment, obtain 2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide；Wherein
The mole dosage ratio of chloracetyl chloride and N- isopropyl -4- fluoroanilines is 1.5:1.
Preferably, the preparation method of described flufenacet, 2- hydroxy-ns-(4- fluoroanilines)-N- in step (7)
(1- Methylethyls) acetamide and 2- methylsulfonyl -5- Trifluoromethyl-1s, the mole dosage ratio of 3,4- thiadiazoles is 1:1.2. the step
In rapid, the present invention is specifically added frerrous chloride, is greatly improved yield, contrast and experiment shows, adds by raw material screening
Frerrous chloride reaction system improves the yield of 9% percentage than frerrous chloride is not added.Therefore the step is in synthesis end-product
There is great meaning during flufenacet.Under alkalescence condition compared with prior art, there is higher yield and synthesis speed
Rate.
Beneficial effect：The present invention screens the preparation method of optimal flufenacet, whole technological design by many experiments
Rationally, optimal reaction condition, including 2- methylsulfonyl -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles, 2- are especially filtered out
The synthesis of acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide, 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- methyl second
Base) acetamide synthesis, 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) synthesis of acetamide and the conjunction of flufenacet
Into raw material the step such as composition, the optimum amount ratios of reaction raw materials, reaction temperature, reaction time, can greatly improve reaction
Yield (up to more than 90%), can reduce side reaction, improve reaction rate, realize that reaction raw materials recycle, significantly lower life
Cost is produced, there is good application prospect.
Brief description of the drawings
Fig. 1 is the synthetic reaction flow chart of flufenacet of the present invention.
Fig. 2 is flufenacet process chart of the present invention.
Embodiment
In the following embodiments, illustrations are carried out to the present invention by way of examples.Tool described by embodiment
Material proportion, process conditions and its result of body are merely to illustrate the present invention, without should be also without limitation in claims
The present invention described in detail.
Embodiment 1：
Such as Fig. 1 and Fig. 2, a kind of preparation method of flufenacet, comprise the following steps：
Step (1)：2,2- methyl mercapto -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Will be stand-by in 3mol trifluoroacetic acids suction trifluoroacetic acid measuring tank, 1mol sulphur hydrazine, first are then added in synthesis reactor
Benzene stirring is cooled to 10~20 DEG C, starts that trifluoroacetic acid is added dropwise, 10~20 DEG C of temperature control during dropwise addition, completion of dropwise addition is in room
The lower stirring reaction of temperature 2 hours, after reaction terminates, then distills, after distillation terminates, obtains colourless liquid, i.e., 2,2- methyl mercaptos -5- three
Methyl fluoride -1,3,4- thiadiazoles (TLC shows consistent Rf values with reference substance)；Yield (93%, purity 96%).
Step (2)：2- methylsulfonyl -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Sodium peroxydisulfate is added to 2,2- methyl mercaptos -5- Trifluoromethyl-1s in the reactor of step (1), 3,4- thiadiazoles
(mol ratio 2:1) water, is pumped into, methanol, is heated up 50 degree, 4 hours is incubated, takes off methanol, cools to 30 degree, centrifugation obtains yellowish
Color flat crystal, i.e. 2- methylsulfonyls -5- Trifluoromethyl-1s, 3,4- thiadiazoles (TLC shows consistent Rf values with reference substance)；Yield
(92%, purity 96%).
Step (3)：The synthesis of N- isopropyl -4- fluoroanilines
By in 4- fluoronitrobenzenes 1mol, acetone 2mol, catalyst thunder nickel input autoclaves, 60 degree are warming up to, is passed through hydrogen,
Pressure maintains 0.7MPA until pressure is constant, cools to 30 degree, filters to obtain catalyst, takes organic phase point to remove moisture, it is different to obtain N-
Propyl group -4- fluoroanilines；(1H-NMR shows 4 hydrogen on the phenyl ring of δ 7.04, the Hydrochemistry signal on the tertiary carbon CH- of δ 4.96, and δ 1.04 is
6 hydrogen signals on two methyl)；Yield (93%, purity 94%).
Step (4)：2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
Will be stand-by in chloracetyl chloride suction chloracetyl chloride measuring tank, step (3) is then added in a kettle to be prepared
N- isopropyl -4- fluoroanilines (1mol), then vacuum be pumped into toluene mixing, chloracetyl chloride is added dropwise into reactor at room temperature
(1.5mol), completion of dropwise addition in about 2 hours, 90 DEG C are warming up to after completion of dropwise addition, and are incubated and terminate to reaction, the chlorine generated in reaction
Change hydrogen and absorbed by tertiary effluent and the hydrochloric acid of by-product 30% is made, after reaction distillation slough unreacted chloracetyl chloride and toluene and mix
Compound recycled, after distillation terminates, cooling adds frozen water washing separation, and aqueous phase goes wastewater treatment, organic phase sodium carbonate
Solution adjusts PH to 6-7, stands to divide and goes aqueous phase to go wastewater treatment, obtains organic phase, as 2- acyl chlorides-N- (4- fluoroanilines)-N- (1-
Methylethyl) acetamide ((1H-NMR shows 4 hydrogen on the phenyl ring of δ 7.07, the Hydrochemistry signal on the tertiary carbon CH- of δ 4.96, δ 1.02
For 6 hydrogen signals on two methyl, 3.59 2 hydrogen of δ are-CH2- upper 2 hydrogen)；Yield (93%, purity 98%).
Step (5)：The synthesis of 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetyl that step (4) is prepared is added in a kettle
Amine 1mol, toluene 3mol, sodium acetate 1.1mol, it is warming up to 95 DEG C and is reacted, distilled after reaction, after distillation terminates, adds water
Washing, stand to divide and go aqueous phase to go wastewater treatment, obtain organic phase, as 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- methyl second
Base) acetamide (1H-NMR shows 4 hydrogen on the phenyl ring of δ 7.09, and the Hydrochemistry signal on the tertiary carbon CH- of δ 4.93, δ 1.01 is two first
6 hydrogen signals on base, 3.79 2 hydrogen of δ are CH2Upper 2 hydrogen of O-, 2.02 be 3 hydrogen signals of methyl)；Yield (96%, purity
95%).
Step (6)：The synthesis of 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) second that step (5) is prepared is added in synthesis reactor
Acid amides (1mol), ethanol (5mol) is added, 70 DEG C of backflows is warming up to, is incubated to reaction and terminates, then distill at ambient pressure to 75
DEG C, ethyl acetate is sloughed, is sold as byproduct, 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) second is produced after distillation
Acid amides (1H-NMR shows 4 hydrogen on the phenyl ring of δ 7.09, the Hydrochemistry signal on the tertiary carbon CH- of δ 4.93, and δ 1.01 is on two methyl
6 hydrogen signals, 3.79 2 hydrogen of δ are CH2Upper 2 hydrogen of O-)；Yield (96%, purity 95%))；Yield (90%, purity
96%).
Step (7)：The synthesis of flufenacet
2- hydroxy-ns-(4- fluoroanilines)-N- (1- methyl second that step (6) is prepared is pumped into reactor with vacuum
Base) acetamide (1mol), frerrous chloride 0.1mol, the 2- methylsulfonyls -5- three that dichloroethanes (3mol) and step (2) are prepared
Methyl fluoride -1,3,4- thiadiazoles (1.2mol), steam heating, react 2 hours under the conditions of normal pressure, 75 DEG C, after reaction terminates, steam
Evaporate to 75 DEG C and slough 1,1- dichloroethanes recycleds, produced after distillation, flufenacet (the fluoro- N- isopropyls -2- [5- (trifluoros of 4-
Glycosides) -1,3,4- thiadiazole -2- imines] acetamide) (MS shows that its molecular weight is 363.3, and high resolution mass spectrum shows its molecular formula
For C14H13F4N3O2S,1H-NMR shows 4 hydrogen on 7,25 phenyl ring, 4.74 display O-CH2- two hydrogen, 1.08 2 methyl of display
6 H, 4.98 show the hydrogen chemical shifts for the CH- that is connected with N).Yield (98%, purity 95%).
The preparation method for the flufenacet that invention provides, the reaction condition of each step, such as reactant species, amount ratio,
Reaction temperature, and reaction time all preferably obtain by experiment, have reaction rate fast, especially yield is high, obtained product
The advantages that purity is high, compared to the prior art achieve good technique effect.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (5)
1. a kind of preparation method of flufenacet, it is characterised in that comprise the following steps：
Step (1)：2,2- methyl mercapto -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Will be stand-by in trifluoroacetic acid suction trifluoroacetic acid measuring tank, sulphur hydrazine is then added in synthesis reactor, toluene stirring is cooled to
10~20 DEG C, start that trifluoroacetic acid, 10~20 DEG C of temperature control during dropwise addition is added dropwise, completion of dropwise addition is stirred at room temperature instead
Should, after reaction terminates, then distill, after distillation terminates, obtain colourless liquid, i.e. 2,2- methyl mercapto -5- Trifluoromethyl-1s, 3,4- thiophenes
Diazole；
Step (2)：2- methylsulfonyl -5- Trifluoromethyl-1s, the synthesis of 3,4- thiadiazoles
Persulfate is added in the reactor of step (1), is pumped into water, methanol, heats up 35~40 degree, be incubated 3~4 hours,
Methanol is taken off, cools to 25~30 degree, centrifugation obtains faint yellow flat crystal, i.e. 2- methylsulfonyls -5- Trifluoromethyl-1s, 3,4- thiophenes
Diazole；
Step (3)：The synthesis of N- isopropyl -4- fluoroanilines
By 4- fluoronitrobenzenes, acetone, catalyst input autoclave in, be warming up to 80 to 90 degree, be passed through hydrogen, cool to 30 to
35 degree, catalyst is filtered to obtain, takes organic phase point to remove moisture, obtains N- isopropyl -4- fluoroanilines；
Step (4)：2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
Chloracetyl chloride is pumped into the N- stand-by in chloracetyl chloride measuring tank, then addition step (3) is prepared in a kettle
Isopropyl -4- fluoroanilines, then the mixing of vacuum suction toluene, is added dropwise chloracetyl chloride, completion of dropwise addition into reactor at room temperature
After be warming up to 80~90 DEG C, and be incubated and terminate to reaction, the hydrogen chloride gas generated in reaction is absorbed by tertiary effluent is made pair
Hydrochloric acid is produced, is distilled after reaction and sloughs unreacted chloracetyl chloride and toluene mixture recycled, after distillation terminates, cooling adds
Frozen water washing separation, aqueous phase go wastewater treatment, and organic phase adjusts PH with aqueous sodium carbonate, stand to divide and go aqueous phase to go wastewater treatment,
Obtain organic phase, as 2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide；
Step (5)：The synthesis of 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide that step (4) is prepared is added in a kettle,
Toluene, sodium acetate, frerrous chloride, it is warming up to 85~95 DEG C and is reacted, distilled after reaction, after distillation terminates, adds water washing,
Standing to divide goes aqueous phase to go wastewater treatment, obtains organic phase, as 2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) second
Acid amides；
Step (6)：The synthesis of 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) acetamide
2- acetyl oxygen-N- (4- fluoroanilines)-N- (1- Methylethyls) acetyl that step (5) is prepared is added in synthesis reactor
Amine, ethanol, 60~70 DEG C of backflows are warming up to, is incubated to reaction and terminates, then distill at ambient pressure to 70~75 DEG C, slough acetic acid
Ethyl ester, sold as byproduct, 2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) acetamide is produced after distillation；
Step (7)：The synthesis of flufenacet
2- hydroxy-ns-(4- fluoroanilines)-N- (1- Methylethyls) second that step (6) is prepared is pumped into reactor with vacuum
Acid amides, frerrous chloride, dichloroethanes, the 2- methylsulfonyl -5- Trifluoromethyl-1s that step (2) is prepared, 3,4- thiadiazoles, steam
Heating, reacts under the conditions of normal pressure, 65 to 75 DEG C, after reaction terminates, distills to 70 to 75 DEG C and sloughs the circulation of 1,1- dichloroethanes
Apply mechanically, produced after distillation, flufenacet (the fluoro- N- isopropyls -2- of 4- [thiadiazole -2- imines of 5- (trifluoro glycosides) -1,3,4-] acetyl
Amine).
2. the preparation method of flufenacet according to claim 1, it is characterised in that in step (1), trifluoroacetic acid and sulphur
The mole dosage ratio of hydrazine is 3:1.
3. the preparation method of flufenacet according to claim 1, it is characterised in that step (3)：By 4- fluoronitrobenzenes,
In acetone, catalyst input autoclave, 80 to 90 degree are warming up to, are passed through hydrogen, pressure maintains 0.6-0.7MPA until pressure
It is constant, 30 degree are cooled to, filters to obtain catalyst, takes organic phase point to remove moisture, obtains N- isopropyl -4- fluoroanilines；Wherein catalyst
For thunder nickel, catalyst amount is the one thousandth mole of 4- fluoronitrobenzenes.
4. the preparation method of flufenacet according to claim 3, it is characterised in that step (4)：Chloracetyl chloride is pumped into
It is stand-by in chloracetyl chloride measuring tank, the N- isopropyl -4- fluoroanilines that step (3) is prepared then are added in a kettle, so
Vacuum is pumped into toluene mixing afterwards, and chloracetyl chloride, completion of dropwise addition in about 2 hours, after completion of dropwise addition is added dropwise into reactor at room temperature
80~90 DEG C are warming up to, and is incubated and terminates to reaction, the hydrogen chloride gas generated in reaction is absorbed by tertiary effluent is made by-product
30% hydrochloric acid, distilled after reaction and slough unreacted chloracetyl chloride and toluene mixture recycled, after distillation terminates, cooling adds
Enter frozen water washing separation, aqueous phase goes wastewater treatment, and it is 6-7 that organic phase adjusts PH with aqueous sodium carbonate, stands to divide and goes aqueous phase to go to give up
Water process, obtain 2- acyl chlorides-N- (4- fluoroanilines)-N- (1- Methylethyls) acetamide；Wherein chloracetyl chloride and N- isopropyls -4-
The mole dosage ratio of fluoroaniline is 1.5:1.
5. the preparation method of flufenacet according to claim 4, it is characterised in that 2- hydroxy-ns-(4- in step (7)
Fluoroaniline)-N- (1- Methylethyls) acetamides and 2- methylsulfonyl -5- Trifluoromethyl-1s, the mole dosage ratio of 3,4- thiadiazoles is
1：1.2.
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| CN115901994A (en) * | 2022-11-01 | 2023-04-04 | 山东京博农化科技股份有限公司 | Method for analyzing content of flufenacet intermediate |
| CN116041200A (en) * | 2022-12-21 | 2023-05-02 | 大连奇凯医药科技有限公司 | Method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1101387C (en) * | 1997-12-12 | 2003-02-12 | 美国拜尔公司 | Process for producing 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole using methyldithio carbazinate and trifluoroacetic acid |
| CN1411719A (en) * | 2001-10-11 | 2003-04-23 | 黑龙江大学化学化工学院 | Heteroepoxyacetamide-2-(1,3-benzothiazole-2-base oxygen)-N-(4-fluorophenyl)-N-(1-methyl ethyl) acetamide weedicide and its preparation |
| CN1142924C (en) * | 1997-12-12 | 2004-03-24 | 美国拜尔公司 | Process for producing thiadiazol acetamides deriv. |
-
2017
- 2017-11-16 CN CN201711137422.3A patent/CN107721948A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1101387C (en) * | 1997-12-12 | 2003-02-12 | 美国拜尔公司 | Process for producing 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole using methyldithio carbazinate and trifluoroacetic acid |
| CN1142924C (en) * | 1997-12-12 | 2004-03-24 | 美国拜尔公司 | Process for producing thiadiazol acetamides deriv. |
| CN1411719A (en) * | 2001-10-11 | 2003-04-23 | 黑龙江大学化学化工学院 | Heteroepoxyacetamide-2-(1,3-benzothiazole-2-base oxygen)-N-(4-fluorophenyl)-N-(1-methyl ethyl) acetamide weedicide and its preparation |
Non-Patent Citations (4)
| Title |
|---|
| 刘宝擅: "氟噻草胺的合成研究", 《河北科技大学硕士学位论文》 * |
| 姜育田等: "氟噻草胺的合成", 《农药》 * |
| 王学玲: "除草剂氟噻草胺的合成工艺研究", 《大连理工大学硕士学位论文》 * |
| 黎育生等: "氟噻草胺的合成", 《现代农药》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108484473A (en) * | 2018-03-01 | 2018-09-04 | 上海优合生物科技有限公司 | A kind of preparation method of N- Phenylindoles ketone |
| CN108715583A (en) * | 2018-08-24 | 2018-10-30 | 盐城师范学院 | A kind of synthetic method of indole derivatives |
| CN111925340A (en) * | 2019-12-16 | 2020-11-13 | 山东金城柯瑞化学有限公司 | Preparation process of methyl mercapto thiadiazole |
| CN111087320A (en) * | 2019-12-27 | 2020-05-01 | 天津阿尔塔科技有限公司 | Preparation method of propisochlor metabolite M5 |
| CN113045444A (en) * | 2021-04-06 | 2021-06-29 | 宁夏常晟药业有限公司 | Synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide |
| CN113461558A (en) * | 2021-06-28 | 2021-10-01 | 宁夏常晟药业有限公司 | Synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide |
| CN115901994A (en) * | 2022-11-01 | 2023-04-04 | 山东京博农化科技股份有限公司 | Method for analyzing content of flufenacet intermediate |
| CN116041200A (en) * | 2022-12-21 | 2023-05-02 | 大连奇凯医药科技有限公司 | Method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide |
| CN116041200B (en) * | 2022-12-21 | 2024-05-28 | 大连奇凯医药科技有限公司 | Method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide |
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