CN107698529A - One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5 - Google Patents

One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5 Download PDF

Info

Publication number
CN107698529A
CN107698529A CN201710788341.3A CN201710788341A CN107698529A CN 107698529 A CN107698529 A CN 107698529A CN 201710788341 A CN201710788341 A CN 201710788341A CN 107698529 A CN107698529 A CN 107698529A
Authority
CN
China
Prior art keywords
cln
reaction
triazole
methyl
ketone
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
Application number
CN201710788341.3A
Other languages
Chinese (zh)
Inventor
不公告发明人
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lianyungang Shijie Agrochemical Co Ltd
Original Assignee
Lianyungang Shijie Agrochemical Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Lianyungang Shijie Agrochemical Co Ltd filed Critical Lianyungang Shijie Agrochemical Co Ltd
Priority to CN201710788341.3A priority Critical patent/CN107698529A/en
Publication of CN107698529A publication Critical patent/CN107698529A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The invention discloses one kind synthesis 1（2,4 dichlorophenyls）The difluoromethyl 1 of 3 methyl 4, 2, the method of the ketone of 4 triazole 5, using o-chloraniline as raw material, pass through diazotising, reduction, adjacent chlorobenzene hydrazonium salt is synthesized into salt, neutralized through alkali into free adjacent chlorophenyl hydrazine, adjacent chlorophenyl hydrazine and acetaldehyde, Zassol, sodium hypochlorite is by condensation, cyclisation and oxidation reaction generation 1 Chloro-O-Phenyl 3 methyl 1H 1, 2, the ketone of 4 triazole 5, the methyl 1H 1 of 1 Chloro-O-Phenyl 3, 2, the ketone of 4 triazole 5 passes through into salt again, fluorine potassium and chlorination reaction obtain 1 (2, 4 two 2 chlorphenyls) 3 methyl, 4 difluoromethyl 1, 2, the ketone of 4 triazole 5 (sulfentrazone intermediate).The synthetic method of the present invention, using o-chloraniline as raw material, it can make that the steric hindrance of synthetic intermediate is small, and impurity is low, so as to improve yield, raw material is easy to get and cost is low, and reaction is gentle, easy to operate, safe, is advantageous to industrialized production.

Description

One kind synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- tri- The method of azoles -5- ketone
Technical field
The present invention relates to herbicide preparing technical field, is specially a kind of synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- Difluoromethyl -1,2, the method for 4- triazole -5- ketone.
Background technology
Sulfentrazone is a kind of herbicide for belonging to difluoromethyl triazolineone, has efficient, low toxicity, the spy of wide spectrum Point, 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone are the important centres for synthesizing sulfentrazone Body, chemical structural formula are as follows：
Current most of manufacturer production is used using phenylhydrazine as initiation material, first synthesizes 1- phenyl -3- methyl -4- difluoro first Base -1,2,4- triazole -5- ketone, then two chlorine generation intermediates on phenyl ring, but such a mode is needed by secondary chlorination, phenyl ring Upper two chlorine is relatively difficult, and impurity is high, and yield is low；In addition it has been raw material also to have with 2,4- dichloroanilines, but due to having on phenyl ring Two chlorine, heterocycle cyclization resistance is big, and yield is low, while fluorine first reaction conversion ratio is also below current level.It is domestic at present existing Technology is disclosed on preparing 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the technique road of 4- triazole -5- ketone Line mainly has following two.
Zhang Yuanyuan et al. discloses synthesis (synthesis of herbicide sulfentrazone, Zhang Yuanyuan etc., the agriculture of herbicide sulfentrazone Medicine is studied and application, the 1st phase, 2008) technique, the synthetic method, for initial feed, through diazotising, contracts with 2,4- dichloroanilines Conjunction, N- are alkylated to obtain sulfentrazone intermediate difluoromethyl Triazolinones, and beneficial effects of the present invention are embodied in reaction raw materials It is easy to get, mild condition is easy to operate, is adapted to industrially utilization and extention；But the synthesis has the shortcomings that certain, with 2,4- dichloros Aniline is raw material, and steric hindrance easily occurs in intermediate product, and product yield is low, while aligns upper chlorine in fluorine first under high temperature Easy dehalogenation, form impurity.
Chinese patent CN106478532A discloses a kind of method for synthesizing difluoromethyl Triazolinones：With adjacent chlorobenzene hydrazonium salt Hydrochlorate is raw material, adjacent chlorophenylhydxazine hydrochloride is dissociated adjacent chlorophenyl hydrazine by alkali, adjacent chlorophenyl hydrazine is after dichloromethane extracts, with former second Sour trimethyl and cyanic acid nak response obtains 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1,2,4- triazole -5- ketone, 1- Chloro-O-Phenyl -3- first Base -1H-1,2,4- triazole -5- ketone are alkylated through N- again, chlorination obtain 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls - 1,2,4- triazole -5- ketone.Beneficial effects of the present invention are embodied in using adjacent chlorophenylhydxazine hydrochloride, make the steric hindrance of intermediate product small, High income, but the shortcomings that certain be present in this method, and the adjacent chlorophenyl hydrazine that dissociates needs to be extracted with dichloromethane, dichloromethane low boiling point, Recovery loss is big, increases cost, higher using trimethyl orthoacetate and potassium cyanate price during cyclization, and chlorination reaction needs Composite catalyst, catalyst reclaimer operation are complicated.
The content of the invention
It is an object of the invention to provide one kind to synthesize 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- The method of triazole -5- ketone, using o-chloraniline as raw material, adjacent chlorobenzene hydrazonium salt is synthesized by diazotising, reduction, into salt, is neutralized through alkali Into free adjacent chlorophenyl hydrazine, adjacent chlorophenyl hydrazine and acetaldehyde, Zassol, sodium hypochlorite are adjacent by condensation, cyclisation and oxidation reaction generation 1- Chlorphenyl -3- methyl isophthalic acids H-1,2,4- triazole -5- ketone, 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1,2,4- triazole -5- ketone again pass through into Salt, fluorine potassium and chlorination reaction obtain 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone (first Sulphur grass amine intermediate), to solve the problems mentioned in the above background technology.
To achieve the above object, the present invention provides following technical scheme：One kind synthesis 1- (2,4- dichlorophenyl) -3- first Base -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, using o-chloraniline as raw material, synthesized by diazotising, reduction, into salt Adjacent chlorobenzene hydrazonium salt, neutralized through alkali into free adjacent chlorophenyl hydrazine, adjacent chlorophenyl hydrazine and acetaldehyde, Zassol, sodium hypochlorite are by condensation, cyclisation 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1 is generated with oxidation reaction, 2,4- triazole -5- ketone, 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1,2, 4- triazole -5- ketone again by into salt, fluorine potassium and chlorination reaction obtain 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls - 1,2,4- triazole -5- ketone (sulfentrazone intermediate).
The further technical scheme of the present invention, comprises the following steps：
(1) adjacent chlorophenylhydxazine hydrochloride synthesis
O-chloraniline is added in the reactor equipped with quantitative hydrochloric acid, reaction temperature is kept at -30-5 DEG C, then to reaction Sodium nitrite solution is added in kettle, with natrium nitrosum diazo-reaction occurs for o-chloraniline, adds ammonium sulfite and sulfurous afterwards Reduction reaction occurs for sour hydrogen ammonium salt solution, generates adjacent chlorophenylhydxazine hydrochloride, and reaction end obtains intermediate 1, and quantitative hydroxide is added dropwise Sodium solution neutralizes, and whole diazotising, reduction, carries out at ambient pressure into salt and neutralization reaction.
Wherein, the intermediate 1 is C6H7ClN2, product C6H7ClN2With water H2O；C6H7ClN2With water H2O mass ratio For 142: 18.
(2) into hydrazone reaction
Into quantitative adjacent chlorophenyl hydrazine is sequentially added in hydrazone reaction kettle under normal temperature, the quantitative solvent tert-butyl alcohol, control temperature is in -5- 10 DEG C are added dropwise quantitative acetaldehyde, -5-10 DEG C of insulated and stirreds 15 minutes, generation intermediate 2 is treated to react in next step.
Wherein, the intermediate 2 is C8H9ClN2, product C8H9ClN2, water H2O；C8H9ClN2, water H2O mass ratio be 168∶18。
(3) cyclization
Above-mentioned intermediate 2 adds quantitative Zassol and quantitative hydrochloric acid, controls temperature in acid condition as -5-10 DEG C of insulations Reaction 2.5 hours, reaction end obtain intermediate 3, treat the next step.
Wherein, the intermediate 3 is C9H10ClN3O, product C9H10ClN3O and sodium chloride nacl；C9H10ClN3O and chlorine The mass ratio for changing sodium NaCl is 422: 117.
(4) oxidation reaction
5-30 DEG C is warming up to, the liquor natrii hypochloritis quantitatively prepared is added dropwise in cyclization product Intermediate 3, was added dropwise Temperature is controlled in journey at 5-30 DEG C.Sodium hypochlorite is dripped, 5-30 DEG C is incubated 30 minutes, and reaction end obtains intermediate 4, treats down Step reaction.
Wherein, the intermediate 4 is C9H8ClN3O, product C9H8ClN3O and sodium chloride nacl, water H2O；C9H8ClN3O With sodium chloride nacl, water H2O mass ratio is 418: 117: 36.
(5) salt-forming reaction
Quantitative DMF and quantitative intermediate 4 are put into reactor, is stirred 0.5 hour, it is fixed then to be put under normal temperature condition Potassium carbonate is measured, 160-165 DEG C is warming up to, insulation reaction 0.5 hour, generates intermediate 5, treats to react in next step.
Wherein, the intermediate 5 is KC9H7ClN3O, product KC9H7ClN3O and carbon dioxide CO2, water H2O； KC9H7ClN3O and carbon dioxide CO2, water H2O mass ratio is 247: 44: 18.
(6) fluorine potassiumization is reacted
Reactor after dehydration is warming up to 180-190 DEG C, is passed through quantitative F-22, insulation reaction 15 minutes, drop Temperature turns material to crystallization kettle and cooled, after centrifugal filtration sylvite, desolvation, obtain intermediate 6, treat to react in next step to 80 DEG C.
Wherein, the intermediate 6 is C10H8ClN3OF2, product C10H8ClN3OF2And potassium chloride (KCl)；C10H8ClN3OF2 Mass ratio with potassium chloride (KCl) is 518: 149.
(7) chlorination reaction
The quantitative DMF of input and quantitative intermediate 6, open air inducing and are passed through quantitative chlorine, temperature control 30-70 in reactor DEG C, lead to chlorine, be incubated 1 hour, obtain 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone (sulfentrazone intermediate).
Preferably, in step (1), the o-chloraniline C6H6NCl, hydrochloric acid HCl, natrium nitrosum NaNO2, ammonium sulfite (NH4)2SO3, ammonium bisulfite NH4HSO3, sodium hydroxide NaOH mass ratio be 254: 73: 138: 232: 198: 80.
Preferably, in step (2), the adjacent chlorophenyl hydrazine C of intermediate 16H7ClN2, acetaldehyde C2H4O mass ratio is 142: 44。
Preferably, in step (3), the C of intermediate 28H9ClN2, Zassol NaOCN, hydrochloric acid HCl mass ratio be 336∶130∶73。
Preferably, in step (4), the C of intermediate 39H10ClN3O, sodium hypochlorite NaClO mass ratio is 422: 149。
Preferably, in step (5), the C of intermediate 49H8ClN3O, potassium carbonate K2CO3Mass ratio be 209: 138.
Preferably, in step (6), the KC of intermediate 59H7ClN3O, F-22 HCF2Cl mass ratio is 494∶173。
Preferably, in step (7), the C of intermediate 610H8ClN3OF2, chlorine Cl2Mass ratio be 259: 71.
Preferably, in step (1-7), the synthesis of adjacent chlorophenylhydxazine hydrochloride, into hydrazone reaction, cyclization, oxidation reaction, into The conversion ratio of reactant salt, the reaction of fluorine potassium and chlorination reaction is all higher than 97%.
Compared with prior art, the beneficial effects of the invention are as follows：
1st, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, Using o-chloraniline as initiation material, one-step chlorination reaction is only needed, can make that the steric hindrance of synthetic intermediate is small, and impurity is low, so as to carry High yield.
2nd, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, The free adjacent chlorophenyl hydrazine that adjacent chlorophenylhydxazine hydrochloride obtains after being neutralized with sodium hydroxide solution, it is not necessary to which organic solvent extracts, directly Next step reaction is carried out with acetaldehyde, it is easy to operate.
3rd, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, Reaction raw materials acetaldehyde and Zassol price are low and be easy to get, and reduce production cost to a certain extent.
4th, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, Chlorination reaction does not need composite catalyst, and problem is reclaimed in the absence of catalyst.
5th, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, Chlorination reaction uses acid DMF solvent, by simple precipitation can direct recovery, it is easy to operate.
6th, present invention synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, It is few to react step number, and each step process mild condition, safe, easy to operate, raw material is cheap and easy to get, and reaction is gentle, operation letter Just, it is advantageously implemented large-scale production.
Brief description of the drawings
Fig. 1 is the sulfentrazone intermediate synthetic reaction equation of the present invention；
The adjacent chlorophenylhydxazine hydrochloride that Fig. 2 is the present invention synthesizes equation；
Fig. 3 is to be of the invention into hydrazone reaction equation；
Fig. 4 is the cyclization equation of the present invention；
Fig. 5 is the oxidation equation formula of the present invention；
Fig. 6 is the salt-forming reaction equation of the present invention；
Fig. 7 is the fluorine potassium reaction equation of the present invention；
Fig. 8 is the chlorination reaction equation of the present invention；
Embodiment
Below in conjunction with the accompanying drawing in the embodiment of the present invention, the technical scheme in the embodiment of the present invention is carried out clear, complete Site preparation describes, it is clear that described embodiment is only part of the embodiment of the present invention, rather than whole embodiments.It is based on Embodiment in the present invention, those of ordinary skill in the art are obtained every other under the premise of creative work is not made Embodiment, belong to the scope of protection of the invention.
Referring to Fig. 1, a kind of synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone Method, using o-chloraniline as raw material, synthesize adjacent chlorobenzene hydrazonium salt by diazotising, reduction, into salt, neutralized through alkali into free adjacent chlorine Phenylhydrazine, adjacent chlorophenyl hydrazine and acetaldehyde, Zassol, sodium hypochlorite are by condensation, cyclisation and oxidation reaction generation 1- Chloro-O-Phenyl -3- first Base -1H-1,2,4- triazole -5- ketone, 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1,2,4- triazole -5- ketone again pass through into salt, fluorine potassium and Chlorination reaction obtains 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, and 4- triazole -5- ketone is (among sulfentrazone Body).
The further technical scheme of the present invention, comprises the following steps：
(1) adjacent chlorophenylhydxazine hydrochloride synthesis
O-chloraniline is added in the reactor equipped with quantitative hydrochloric acid, reaction temperature is kept at -30-5 DEG C, then to reaction Sodium nitrite solution is added in kettle, with natrium nitrosum diazo-reaction occurs for o-chloraniline, adds ammonium sulfite and sulfurous afterwards Reduction reaction occurs for sour hydrogen ammonium salt solution, generates adjacent chlorophenylhydxazine hydrochloride, and reaction end obtains intermediate 1, and quantitative hydroxide is added dropwise Sodium solution neutralizes, and whole diazotising, reduction, carries out at ambient pressure into salt and neutralization reaction.
Wherein, the intermediate 1 is C6H7ClN2, product C6H7ClN2With water H2O；C6H7ClN2With water H2O mass ratio For 142: 18.
Wherein, the o-chloraniline C6H6NCl, hydrochloric acid HCl, natrium nitrosum NaNO2, ammonium sulfite (NH4)2SO3, sulfurous acid Hydrogen ammonium NH4HSO3, sodium hydroxide NaOH mass ratio be 254: 73: 138: 232: 198: 80.
(2) into hydrazone reaction
Into quantitative adjacent chlorophenyl hydrazine is sequentially added in hydrazone reaction kettle under normal temperature, the quantitative solvent tert-butyl alcohol, control temperature is in -5- 10 DEG C are added dropwise quantitative acetaldehyde, -5-10 DEG C of insulated and stirreds 15 minutes, generation intermediate 2 is treated to react in next step.
Wherein, the intermediate 2 is C8H9ClN2, product C8H9ClN2, water H2O；C8H9ClN2, water H2O mass ratio be 168∶18。
Wherein, the adjacent chlorophenyl hydrazine C of the intermediate 16H7ClN2, acetaldehyde C2H4O mass ratio is 142: 44.
(3) cyclization
Above-mentioned intermediate 2 adds quantitative Zassol and quantitative hydrochloric acid, controls temperature in acid condition as -5-10 DEG C of insulations Reaction 2.5 hours, reaction end obtain intermediate 3, treat the next step.
Wherein, the intermediate 3 is C9H10ClN3O, product C9H10ClN3O and sodium chloride nacl；C9H10ClN3O and chlorine The mass ratio for changing sodium NaCl is 422: 117.
Wherein, the C of intermediate 28H9ClN2, Zassol NaOCN, hydrochloric acid HCl mass ratio be 336: 130: 73.
(4) oxidation reaction
5-30 DEG C is warming up to, the liquor natrii hypochloritis quantitatively prepared is added dropwise in cyclization product Intermediate 3, was added dropwise Temperature is controlled in journey at 5-30 DEG C.Sodium hypochlorite is dripped, 5-30 DEG C is incubated 30 minutes, and reaction end obtains intermediate 4, treats down Step reaction.
Wherein, the intermediate 4 is C9H8ClN3O, product C9H8ClN3O and sodium chloride nacl, water H2O；C9H8ClN3O With sodium chloride nacl, water H2O mass ratio is 418: 117: 36.
Wherein, the C of intermediate 39H10ClN3O, sodium hypochlorite NaClO mass ratio is 422: 149.
(5) salt-forming reaction
Quantitative DMF and quantitative intermediate 4 are put into reactor, is stirred 0.5 hour, it is fixed then to be put under normal temperature condition Potassium carbonate is measured, 160-165 DEG C is warming up to, insulation reaction 0.5 hour, generates intermediate 5, treats to react in next step.
Wherein, the intermediate 5 is KC9H7ClN3O, product KC9H7ClN3O and carbon dioxide CO2, water H2O； KC9H7ClN3O and carbon dioxide CO2, water H2O mass ratio is 247: 44: 18.
Wherein, the C of intermediate 49H8ClN3O, potassium carbonate K2CO3Mass ratio be 209: 138.
(6) fluorine potassiumization is reacted
Reactor after dehydration is warming up to 180-190 DEG C, is passed through quantitative F-22, insulation reaction 15 minutes, drop Temperature turns material to crystallization kettle and cooled, after centrifugal filtration sylvite, desolvation, obtain intermediate 6, treat to react in next step to 80 DEG C.
Wherein, the intermediate 6 is C10H8ClN3OF2, product C10H8ClN3OF2And potassium chloride (KCl)；C10H8ClN3OF2 Mass ratio with potassium chloride (KCl) is 518: 149.
Wherein, the KC of intermediate 59H7ClN3O, F-22 HCF2Cl mass ratio is 494: 173.
(7) chlorination reaction
The quantitative DMF of input and quantitative intermediate 6, open air inducing and are passed through quantitative chlorine, temperature control 30-70 in reactor DEG C, lead to chlorine, be incubated 1 hour, obtain 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone (sulfentrazone intermediate).
Wherein, the C of intermediate 610H8ClN3OF2, chlorine Cl2Mass ratio be 259: 71.
In step (1-7), the synthesis of adjacent chlorophenylhydxazine hydrochloride, into hydrazone reaction, cyclization, oxidation reaction, salt-forming reaction, The conversion ratio of the reaction of fluorine potassium and chlorination reaction is all higher than 97%.
The foregoing is only a preferred embodiment of the present invention, but protection scope of the present invention be not limited thereto, Any one skilled in the art the invention discloses technical scope in, technique according to the invention scheme and its Inventive concept is subject to equivalent substitution or change, should all be included within the scope of the present invention.

Claims (10)

1. one kind synthesis 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, the method for 4- triazole -5- ketone, its feature It is, using o-chloraniline as raw material, synthesizes adjacent chlorobenzene hydrazonium salt by diazotising, reduction, into salt, neutralized through alkali into free adjacent chlorobenzene Hydrazine, adjacent chlorophenyl hydrazine and acetaldehyde, Zassol, sodium hypochlorite are by condensation, cyclisation and oxidation reaction generation 1- Chloro-O-Phenyl -3- first Base -1H-1,2,4- triazole -5- ketone, 1- Chloro-O-Phenyl -3- methyl isophthalic acids H-1,2,4- triazole -5- ketone again pass through into salt, fluorine potassium and Chlorination reaction obtains 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2, and 4- triazole -5- ketone is (among sulfentrazone Body).
2. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 1,4- triazole -5- ketone Synthetic method, it is characterised in that：Synthetic method comprises the following steps：
(1) adjacent chlorophenylhydxazine hydrochloride synthesis
O-chloraniline is added in the reactor equipped with quantitative hydrochloric acid, reaction temperature is kept at -30-5 DEG C, then into reactor Sodium nitrite solution is added, with natrium nitrosum diazo-reaction occurs for o-chloraniline, adds ammonium sulfite and bisulfite afterwards Reduction reaction occurs for ammonium salt solution, generates adjacent chlorophenylhydxazine hydrochloride, and reaction end obtains intermediate 1, and it is molten that quantitative sodium hydroxide is added dropwise Liquid neutralizes, and whole diazotising, reduction, carries out at ambient pressure into salt and neutralization reaction.
Wherein, the intermediate 1 is C6H7ClN2, product C6H7ClN2With water H2O；C6H7ClN2With water H2O mass ratio is 142 ∶18。
(2) into hydrazone reaction
Into quantitative adjacent chlorophenyl hydrazine is sequentially added in hydrazone reaction kettle under normal temperature, the quantitative solvent tert-butyl alcohol, control temperature is at -5-10 DEG C It is added dropwise quantitative acetaldehyde, -5-10 DEG C of insulated and stirreds 15 minutes, generation intermediate 2 is treated to react in next step.
Wherein, the intermediate 2 is C8H9ClN2, product C8H9ClN2, water H2O；C8H9ClN2, water H2O mass ratio be 168: 18。
(3) cyclization
Above-mentioned intermediate 2 adds quantitative Zassol and quantitative hydrochloric acid, and it is -5-10 DEG C of insulation reactions to control temperature in acid condition 2.5 hours, reaction end obtained intermediate 3, treats the next step.
Wherein, the intermediate 3 is C9H10ClN3O, product C9H10ClN3O and sodium chloride nacl；C9H10ClN3O and sodium chloride NaCl mass ratio is 422: 117.
(4) oxidation reaction
5-30 DEG C is warming up to, the liquor natrii hypochloritis quantitatively prepared is added dropwise in cyclization product Intermediate 3, during dropwise addition Temperature is controlled at 5-30 DEG C.Sodium hypochlorite is dripped, 5-30 DEG C is incubated 30 minutes, and reaction end obtains intermediate 4, treats that lower step is anti- Should.
Wherein, the intermediate 4 is C9H8ClN3O, product C9H8ClN3O and sodium chloride nacl, water H2O；C9H8ClN3O and chlorination Sodium NaCl, water H2O mass ratio is 418: 117: 36.
(5) salt-forming reaction
Quantitative DMF and quantitative intermediate 4 are put into reactor, stirs 0.5 hour, quantitative carbon is then put under normal temperature condition Sour potassium, 160-165 DEG C is warming up to, insulation reaction 0.5 hour, generates intermediate 5, treat to react in next step.
Wherein, the intermediate 5 is KC9H7ClN3O, product KC9H7ClN3O and carbon dioxide CO2, water H2O；KC9H7ClN3O and Carbon dioxide CO2, water H2O mass ratio is 247: 44: 18.
(6) fluorine potassiumization is reacted
Reactor after dehydration is warming up to 180-190 DEG C, quantitative F-22 is passed through, insulation reaction 15 minutes, is cooled to 80 DEG C, turn material to crystallization kettle and cool, after centrifugal filtration sylvite, desolvation, obtain intermediate 6, treat to react in next step.
Wherein, the intermediate 6 is C10H8ClN3OF2, product C10H8ClN3OF2And potassium chloride (KCl)；C10H8ClN3OF2And chlorine The mass ratio for changing potassium KCl is 518: 149.
(7) chlorination reaction
The quantitative DMF of input and quantitative intermediate 6 in reactor, open air inducing and are passed through quantitative chlorine, 30-70 DEG C of temperature control, lead to Complete chlorine, 1 hour is incubated, obtains 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2,4- triazole -5- ketone (first sulphurs Careless amine intermediate).
3. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (1), the o-chloraniline C6H6NCl, hydrochloric acid HCl, natrium nitrosum NaNO2, sulfurous Sour ammonium (NH4)2SO3, ammonium bisulfite NH4HSO3, sodium hydroxide NaOH mass ratio be 254: 73: 138: 232: 198: 80.
4. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (2), the adjacent chlorophenyl hydrazine C of intermediate 16H7ClN2, acetaldehyde C2H4O mass ratio is 142∶44。
5. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (3), the C of intermediate 28H9ClN2, Zassol NaOCN, hydrochloric acid HCl quality Than for 336: 130: 73.
6. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (4), the C of intermediate 39H10ClN3O, sodium hypochlorite NaClO mass ratio is 422∶149。
7. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (5), the C of intermediate 49H8ClN3O, potassium carbonate K2CO3Mass ratio be 209: 138。
8. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (6), the KC of intermediate 59H7ClN3O, F-22 HCF2Cl matter Amount is than being 494: 173.
9. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (7), the intermediate 6C10h8ClN3OF2, chlorine Cl2Mass ratio be 259: 71。
10. 1- (2,4- dichlorophenyl) -3- methyl -4- difluoromethyls -1,2 according to claim 2,4- triazole -5- ketone Synthetic method, it is characterised in that：In step (1-7), adjacent chlorophenylhydxazine hydrochloride synthesis, into hydrazone reaction, cyclization, oxidation Reaction, salt-forming reaction, the conversion ratio of the reaction of fluorine potassium and chlorination reaction are all higher than 97%.
CN201710788341.3A 2017-08-23 2017-08-23 One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5 Pending CN107698529A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710788341.3A CN107698529A (en) 2017-08-23 2017-08-23 One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710788341.3A CN107698529A (en) 2017-08-23 2017-08-23 One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5

Publications (1)

Publication Number Publication Date
CN107698529A true CN107698529A (en) 2018-02-16

Family

ID=61171984

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710788341.3A Pending CN107698529A (en) 2017-08-23 2017-08-23 One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5

Country Status (1)

Country Link
CN (1) CN107698529A (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114149342A (en) * 2021-11-02 2022-03-08 浙大宁波理工学院 N- (2, 4-dichloro-5-hydrazinophenyl) acetamide compound and synthesis method thereof
CN114315744A (en) * 2022-01-11 2022-04-12 浙大宁波理工学院 Synthetic method of sulfentrazone intermediate
CN114805229A (en) * 2021-01-21 2022-07-29 兰州大学 Preparation of 1,2, 4-triazoles

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143838A (en) * 2007-10-29 2008-03-19 太仓市华联化工实业有限公司 Preparation method for 2-chlorophenylhydrazine
CN103965124A (en) * 2014-04-29 2014-08-06 安徽苏启化工有限公司 Synthetic method for triazoline-ketone
CN106478532A (en) * 2016-08-27 2017-03-08 江苏瑞邦农药厂有限公司 A kind of method of synthesis sulfentrazone

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143838A (en) * 2007-10-29 2008-03-19 太仓市华联化工实业有限公司 Preparation method for 2-chlorophenylhydrazine
CN103965124A (en) * 2014-04-29 2014-08-06 安徽苏启化工有限公司 Synthetic method for triazoline-ketone
CN106478532A (en) * 2016-08-27 2017-03-08 江苏瑞邦农药厂有限公司 A kind of method of synthesis sulfentrazone

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114805229A (en) * 2021-01-21 2022-07-29 兰州大学 Preparation of 1,2, 4-triazoles
CN114805229B (en) * 2021-01-21 2023-04-25 兰州大学 Preparation of 1,2, 4-triazole
CN114149342A (en) * 2021-11-02 2022-03-08 浙大宁波理工学院 N- (2, 4-dichloro-5-hydrazinophenyl) acetamide compound and synthesis method thereof
CN114315744A (en) * 2022-01-11 2022-04-12 浙大宁波理工学院 Synthetic method of sulfentrazone intermediate

Similar Documents

Publication Publication Date Title
CN107698529A (en) One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5
CN106478532B (en) A method of synthesis sulfentrazone
CN103951627B (en) Method for synthesizing sulfentrazone midbody and sulfentrazone
CN110799503A (en) Synthesis of mecamitocainide
CN107629015A (en) One kind synthesis 1（2,4 dichlorophenyls）The method of the ketone of 3 methyl, 4 difluoromethyl, 1,2,4 triazole 5
KR101273895B1 (en) Process for preparing amino-triazolinone
CN101100450A (en) Method for preparing ethylsulfonyl acetonitrile
CN109970571B (en) Synthesis process of 2- (4-chlorphenyl) aniline
CN108997203B (en) Efficient purification method of 2, 3-dichloro-5-trifluoromethylpyridine
CN109796419B (en) Preparation method of sulfentrazone through catalytic coupling of copper reagent
CN108610290B (en) Preparation method of fluxapyroxad
CN106632014A (en) Preparation of 2-amino-5-chloropyridine
CN109748878A (en) A kind of sulfentrazone key intermediate benzene connects the preparation method of triazolinones derivative
CN103288708B (en) The preparation method of 1- aryl -2- indolinone derivative
US4335260A (en) Process for the preparation of N-di-n-propyl-2,6-dinitro-4-trifluoromethylaniline having a low content of nitrosamines
CN103833660B (en) The preparation method of lamotrigine and intermediate thereof
CN105175294B (en) Method for synthesizing sulfanilamide by using chlorobenzene as raw material
KR100345874B1 (en) Method for synthesizing hydrazodicarbonamide
CA2075805C (en) Novel process for producing semicarbazide
TWI564292B (en) For the preparation of N-substituted pyrazole compounds
CN107556254A (en) A kind of synthetic method of sulfentrazone
CN111004184A (en) Synthesis process of 4, 6-dichloropyrimidine
US6133447A (en) Process for the preparation of substituted pyridines
CN112679378B (en) Preparation method of oxadiazon intermediate 2,4-dichloro-5-isopropoxyphenylhydrazine
CN114478326B (en) Synthesis method of saflufenacil key intermediate

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
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20180216