CN110343057A - A kind of synthetic method of Hexanaphthene flusulfamide - Google Patents
A kind of synthetic method of Hexanaphthene flusulfamide Download PDFInfo
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- CN110343057A CN110343057A CN201910594457.2A CN201910594457A CN110343057A CN 110343057 A CN110343057 A CN 110343057A CN 201910594457 A CN201910594457 A CN 201910594457A CN 110343057 A CN110343057 A CN 110343057A
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- oxocyclohexyl
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- 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
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
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- 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
- C07C303/38—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 reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Abstract
The present invention provides a kind of methods of synthesizing cyclohexane 1 flusulfamide, and 2- oxocyclohexyl sulfonate is made method includes the following steps: cyclohexanone is reacted through the halogenated cyclohexanone of halogenated product 2- with sulphite；It reacts to obtain Hexanaphthene flusulfamide with oxalyl chloride, 2- trifluoromethyl -4- chloroaniline again.In the present invention, cyclohexanone and sulfur trioxide Isosorbide-5-Nitrae-dioxane compound are replaced with the halogenated cyclohexanone of 2- and sulphite, avoided using BaCl2Or Ba (OH)2Precipitating removes SO4 2‑It is difficult to control the BaSO of chemical reaction terminal and generation4The problem of cannot being utilized and becoming the three wastes is precipitated, the storage of burn into difficulty, difficult operation, strong and stimulating peculiar smell and easy the disadvantages of causing poisoning of ammonia are overcome.Method reaction condition of the invention is mild, easy to operate, product purity height, high income；Suitable for large-scale industrialization application.
Description
Technical field
The present invention relates to the compound N-in agrochemicals field (2- trifluoromethyl-4-chlorophenyl) -2- oxocyclohexyl sulphurs
A kind of chemical industry synthesis technology of amide (abbreviation Hexanaphthene flusulfamide in the present invention).
Background technique
Hexanaphthene flusulfamide is to can be used in preventing and treating tomato ash in the new type bactericide of discovery in 2004 by China Agricultural University
The multiple kinds of crops disease such as mildew, sclerotinia sclerotiorum, Cucumber Target Leaf Spot, scab.The general formula of molecular structure of its series compound
And compounding techniques number of patent application be 200510085408.4 in " 2- keto naphthene sulfamide amine, preparation method and
Give disclosure in purposes as a fungicide " text.In the invention, 2- oxocyclohexyl sulfonic acid is first synthesized using cyclohexanone as raw material
Sylvite intermediate after 2- oxocyclohexyl sulfonic acid chloride is made in the latter and oxalyl chloride, then reacts i.e. with 2- trifluoromethyl -4- chloroaniline
It obtains Hexanaphthene flusulfamide (WL-IIA-12).In the synthetic technology, BaCl is used2Precipitating removes SO4 2-, it is difficult to reaction end is controlled,
Generate a large amount of solid waste BaSO4Precipitating, needs KOH solution that 2- oxocyclohexyl sulfonic acid is converted to sylvite.The report such as Zhang Haibin in 2012
Road uses Ba (OH)2Precipitate H2SO4(pesticide, 2012,51 (4), 287-288), the method equally exists the above problem.
" synthetic method of Hexanaphthene flusulfamide ", the hair are disclosed in the specification that number of patent application is 201210346240.8
Bright reacted using cyclohexanone, 1,4- dioxane, sulfur trioxide, oxalyl chloride, ammonia, 2- trifluoromethyl -4- chloroaniline as raw material is made
?.The method replaces the precipitation reagent BaCl in former synthetic technology with ammonia2Or Ba (OH)2With salt-forming reagent KOH solution, but make
With ammonia, there are deep-etching, difficult storage, difficult operation, strong and stimulating peculiar smell and easy the problems such as causing poisoning.
Therefore, continue to reinforce to carry out the Hexanaphthene flusulfamide containing trifluoromethyl synthetic technology research optimization have it is academic and
Industrialized double meaning.
Summary of the invention
The object of the present invention is to provide a kind of high yield, easy to operate, environmental-friendly Hexanaphthene flusulfamide new synthesis technology, gram
Take the defect that the existing Hexanaphthene flusulfamide synthetic technology three wastes are more, operation is difficult to control, condition is harsh.
A kind of synthetic method of Hexanaphthene flusulfamide, with the halogenated cyclohexanone of 2-, sulphite, oxalyl chloride, 2- trifluoromethyl -4-
Hexanaphthene flusulfamide is prepared by reaction for raw material in chloroaniline.
Above-mentioned synthetic method, it is further improved, the synthetic method the following steps are included:
S1, the halogenated cyclohexanone of 2- is reacted to obtained 2- oxocyclohexyl sulfonate with sulphite；
S2,2- oxocyclohexyl sulfonate obtained in the step S1 is reacted to obtained 2- oxocyclohexyl with oxalyl chloride
Sulfonic acid chloride；
S3, by 2- oxocyclohexyl sulfonic acid chloride obtained in the step S2 and the 2- trifluoromethyl -4- chloroaniline system of reacting
Obtain Hexanaphthene flusulfamide.
Above-mentioned synthetic method, it is further improved, in the step S1, in the halogenated cyclohexanone of 2- X be Cl, Br,
One of which in I；The sulphite is at least one of ammonium sulfite, sodium sulfite, potassium sulfite.
Above-mentioned synthetic method, further improved, the halogenated cyclohexanone of 2- is made by cyclohexanone through halogenation.
Above-mentioned synthetic method, further improved, in the step S1, the halogenated cyclohexanone of the 2- and sulphite exist
It is reacted in solvent, the solvent is water and/or alcohol；The reaction carries out under nitrogen or argon；In the reaction process
Control temperature≤solvent boiling point of reaction system；The time of the reaction is 20h.
Above-mentioned synthetic method, it is further improved, in the step S1, reaction system is controlled in the reaction process
Temperature is 15 DEG C~100 DEG C.
Above-mentioned synthetic method, further improved, the step S2 specifically: by 2- oxocyclohexyl sulfonate and instead
It answers solvent A to mix, oxalyl chloride is added dropwise in gained 2- oxocyclohexyl sulfonate solution, catalyst is added, in nitrogen or argon gas
It is reacted under protection, obtains 2- oxocyclohexyl chloride solution.
Above-mentioned synthetic method, further improved, the reaction solvent A is halogenated aryl hydrocarbon or halogenated alkane；The halogen
It is methylene chloride and/or 1,2- dichloroethanes for alkane；The catalyst is N,N-dimethylformamide；The drop of the oxalyl chloride
Control system temperature is -10 DEG C~5 DEG C during adding；The time of the reaction is 6h；In the step S2 after the reaction was completed
It further include dry air being advertised into reaction system or inert gas is purged.
Above-mentioned synthetic method, further improved, the step S3 specifically: by 2- trifluoromethyl -4- chloroaniline with
Reaction dissolvent B is mixed, and acid binding agent is added in gained 2- trifluoromethyl -4- chlorobenzene amine aqueous solution, is added dropwise to 2- obtained in step S2
Oxocyclohexyl chloride solution carries out reacting obtained Hexanaphthene flusulfamide.
Above-mentioned synthetic method, further improved, the reaction dissolvent B is halogenated aryl hydrocarbon or halogenated alkane；The halogen
It is methylene chloride and/or 1,2- dichloroethanes for alkane；The acid binding agent is at least one of carbonate, triethylamine, pyridine；
Control system temperature is -5 DEG C~10 DEG C during the dropwise addition of the 2- oxocyclohexyl chloride solution；The reaction when
Between be 5h；In the step S3 further includes successively being carried out with hydrochloric acid solution and water to gained reaction solution after reaction after the reaction was completed
Extraction, gained organic phase are dried and evaporated solvent with anhydrous sodium sulfate, and petroleum ether mashing is added, and filtering obtains Hexanaphthene flusulfamide.
In the application synthetic method, specific chemical equation is as follows:
A:
B:
C:
The invention has the characteristics that the present invention substitutes hexamethylene in the prior art with reacting for sulphite with the halogenated cyclohexanone of 2-
Ketone is reacted with sulfur trioxide Isosorbide-5-Nitrae-dioxane compound is directly made 2- oxocyclohexyl sulfonate, avoids addition and removes
Remove SO4 2-Precipitating reagent BaCl2Or Ba (OH)2And the process of salt forming agent KOH solution；Compared with the method in existing literature, we
The 2- oxocyclohexyl sulfonate preparation process condition of method is mild, easy to operate, reduces three waste discharge, and product yield is high, real
Clean manufacturing is showed；The synthetic method can be used in industrialized production and application, and the compound of synthesis can be widely applied for preventing kind
The multiple kinds of crops disease such as solanum cinerea, sclerotinia sclerotiorum, Cucumber Target Leaf Spot, scab.
Detailed description of the invention
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention
In attached drawing, the technical scheme in the embodiment of the invention is clearly and completely described.
Fig. 1 is the H NMR spectra of 2- oxocyclohexyl sodium sulfonate obtained in the embodiment of the present invention 1.
Fig. 2 is the C NMR spectra of 2- oxocyclohexyl sodium sulfonate obtained in the embodiment of the present invention 1.
Fig. 3 is the H NMR spectra of Hexanaphthene flusulfamide obtained in the embodiment of the present invention 1.
Fig. 4 is the C NMR spectra of Hexanaphthene flusulfamide obtained in the embodiment of the present invention 1.
The present invention is described in further details below with reference to specific example.
Specific embodiment
Method therefor is conventional method unless otherwise specified in following implementations.
Embodiment:
In the present invention, the specific synthetic method of Hexanaphthene flusulfamide can be decomposed into following 3 process engineerings:
(1) preparation of 2- oxocyclohexyl sodium sulfonate
2- chlorine cyclohexanone 13.26g (100mmol), anhydrous sodium sulfite 18.91g (150mmol) and 300ml water are mixed
Return stirring 20 hours at 100 DEG C are fitted into 500ml round-bottomed flask.After complete reaction, reaction solution is cooled to 40 DEG C or so
When, solvent rotary evaporated to dryness is dry.500ml dehydrated alcohol is added in raffinate to add after being sufficiently evaporated remaining moisture
Anhydrous ether-n-hexane the 200ml for entering 1:1, filters after a period of time is stirred at room temperature, and is dried under reduced pressure to obtain 2- oxocyclohexyl sulfonic acid
Sodium crude product is directly used in and reacts in next step.
(2) preparation of 2- oxocyclohexyl sulfonic acid chloride
Above-mentioned gained 2- oxocyclohexyl sodium sulfonate, methylene chloride (100 mL), N, N- are added into 500ml round-bottomed flask
Dimethylformamide (1mL), ice-water bath is cooled to -5 DEG C, is slowly added dropwise oxalyl chloride (10ml, 100mmol), dropping temperature control
At 0 DEG C hereinafter, being reacted at room temperature after being added dropwise 6 hours.Dry air purged solution.Liquid is saved backup in 5 DEG C or less.
(3) preparation of N- (2- trifluoromethyl-4-chlorophenyl) -2- oxocyclohexyl sulfonamide (Hexanaphthene flusulfamide)
In 500ml round-bottomed flask, 2- trifluoromethyl -4- chloroaniline (17.55g, 90mmol), triethylamine is added
(19.5mL, 130mmol), methylene chloride (50ml), ice-water bath is cooled to -5 DEG C, and above-mentioned gained chloride solution is slowly added dropwise,
Dropping temperature control is 0-5 DEG C, is reacted at room temperature 5 hours after being added dropwise.TLC monitors reaction process, and raw material fully reacting stops
Only react.Reaction solution is successively used 6mol/L hydrochloric acid solution (100ml), water (100mL × 2) extraction, organic phase anhydrous sodium sulfate
Dry, rotary evaporation of solvent obtains crude product, and petroleum ether and stirring mashing is added, filters and obtains Hexanaphthene flusulfamide, total recovery 63% (with
2- chlorine cyclohexanone meter).
Claims (10)
1. a kind of synthetic method of Hexanaphthene flusulfamide, which is characterized in that with the halogenated cyclohexanone of 2-, sulphite, oxalyl chloride, 2- tri-
Hexanaphthene flusulfamide is prepared by reaction for raw material in methyl fluoride -4- chloroaniline.
2. synthetic method according to claim 1, which is characterized in that the synthetic method the following steps are included:
S1, the halogenated cyclohexanone of 2- is reacted to obtained 2- oxocyclohexyl sulfonate with sulphite；
S2,2- oxocyclohexyl sulfonate obtained in the step S1 is reacted to obtained 2- oxocyclohexyl sulphonyl with oxalyl chloride
Chlorine；
S3,2- oxocyclohexyl sulfonic acid chloride obtained in the step S2 is reacted to obtained ring with 2- trifluoromethyl -4- chloroaniline
Own flusulfamide.
3. synthetic method according to claim 2, which is characterized in that in the step S1, X in the halogenated cyclohexanone of 2-
For the one of which in Cl, Br, I；The sulphite is at least one of ammonium sulfite, sodium sulfite, potassium sulfite.
4. synthetic method according to claim 3, which is characterized in that the halogenated cyclohexanone of 2- is anti-through halogenation by cyclohexanone
It should be made.
5. the synthetic method according to any one of claim 2~4, which is characterized in that in the step S1, the 2- halogen
It is reacted in a solvent for cyclohexanone with sulphite, the solvent is water and/or alcohol；The reaction is under nitrogen or argon
It carries out；Temperature≤solvent boiling point of reaction system is controlled in the reaction process；The time of the reaction is 15~30 hours,
It is preferred that 20 hours.
6. synthetic method according to claim 5, which is characterized in that in the step S1, controlled in the reaction process
The temperature of reaction system is 15 DEG C~100 DEG C.
7. the synthetic method according to any one of claim 2~4, which is characterized in that the step S2 specifically: by 2-
Oxocyclohexyl sulfonate is mixed with reaction solvent A, is added dropwise to oxalyl chloride in gained 2- oxocyclohexyl sulfonate solution, is added
Catalyst is reacted under nitrogen or argon, obtains 2- oxocyclohexyl chloride solution.
8. synthetic method according to claim 7, which is characterized in that the reaction solvent A is halogenated aryl hydrocarbon or alkyl halide
Hydrocarbon；The halogenated alkane is methylene chloride and/or 1,2- dichloroethanes；The catalyst is N,N-dimethylformamide；It is described
Control system temperature is -10 DEG C~5 DEG C during the dropwise addition of oxalyl chloride；The time of the reaction is 4~10 hours, and preferably 6 is small
When；In the step S2 further includes dry air being advertised into reaction system or inert gas is purged after the reaction was completed.
9. synthetic method according to claim 7, which is characterized in that the step S3 specifically: by 2- trifluoromethyl -4-
Chloroaniline is mixed with reaction dissolvent B, and acid binding agent is added in gained 2- trifluoromethyl -4- chlorobenzene amine aqueous solution, is added dropwise in step S2
Obtained 2- oxocyclohexyl chloride solution carries out reacting obtained Hexanaphthene flusulfamide.
10. synthetic method according to claim 9, which is characterized in that the reaction dissolvent B is halogenated aryl hydrocarbon or alkyl halide
Hydrocarbon；The halogenated alkane is methylene chloride and/or 1,2- dichloroethanes；The acid binding agent is carbonate, in triethylamine, pyridine
It is at least one；Control system temperature is -5 DEG C~10 DEG C during the dropwise addition of the 2- oxocyclohexyl chloride solution；It is described
The time of reaction is 3~10 hours, preferably 5 hours；In the step S3 further includes anti-to gained after reaction after the reaction was completed
Liquid is answered successively to be extracted with hydrochloric acid solution and water, gained organic phase is dried and evaporated solvent with anhydrous sodium sulfate, and petroleum ether is added
Mashing, filtering, obtains Hexanaphthene flusulfamide.
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2019
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