CN106187840A - A kind of indanone compounds of band trifluoromethylthio and preparation method thereof - Google Patents
A kind of indanone compounds of band trifluoromethylthio and preparation method thereof Download PDFInfo
- Publication number
- CN106187840A CN106187840A CN201610547078.4A CN201610547078A CN106187840A CN 106187840 A CN106187840 A CN 106187840A CN 201610547078 A CN201610547078 A CN 201610547078A CN 106187840 A CN106187840 A CN 106187840A
- Authority
- CN
- China
- Prior art keywords
- reaction
- trifluoromethylthio
- preparation
- compounds
- indanone
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses the preparation method of the indanone compounds of a kind of band trifluoromethylthio, the method chooses acetylenic ketone compounds and fluoroform sulfane alcohol silver compound is raw material, using persulfate reagent as oxidant, with HMPA as stabilizer, in reaction dissolvent, it is 80 in reaction temperatureoReact under C, reaction 12h, reaction obtains indanone compounds through post processing after terminating, this preparation method solves and solves amide-type heterocycle and directly generate the technical barrier of indanone compounds, and this preparation method have economical save money, stability is high, reaction condition is gentle, the response time is short, cheaper starting materials is easy to get, product yield and the plurality of advantages such as purity is high.
Description
Technical field
The invention belongs to organic chemical synthesis technical field, relate to a kind of band trifluoromethylthio indanone compounds and
Preparation method.
Background technology
Trifluoromethylthio (-SCF3) has strong sucting electronic effect, highly lipophilic (Hydrophobic Parameters) and good
The characteristics such as good biological activity, therefore be introduced in organic compound and can significantly change compound chemical stability and generation
Thank to stability.Therefore, containing-SCF3The compound of base has the most potential in medicine, the field such as agricultural chemicals and material
Using value.Such as, Coccidiostatic Drug Toltrazuril (Toltrazuril), insecticide (Vaniliprole) and loss of appetite
Medicine tiflorex (Tiflorex), antihypertensive losartan (Losartan analogue) etc., all contain fluoroform
Sulfenyl, shown in following science of culture structural formula:
Good characteristic based on trifluoromethylthio, people are interest widely to trifluoromethylthio reaction and display.Such as, research
Personnel have researched and developed and have been prepared for multiple arylation, alkylene, and carbonylation etc. is with the related compound of trifluoromethylthio.
Arylation reaction, the fluoroform mercaptan CF found such as Harris3The SH additive reaction to fluoroolefins, this reaction is at X
Ray or ultraviolet irradiate lower generation trifluoromethylthio free radical and then fluoroolefins are carried out addition.But it is difficult to there is raw material in this reaction
With shortcomings such as preservation, reaction condition more harshnesses；As Billard usesN-The indole of trifluoro-methylthio aniline and electron rich is to first
There is electrophilic reaction in the presence of benzenesulfonic acid and solvent DCM, carry out olefination, generate the substituted indoles of trifluoromethylthio
Compound；But but due toN-Trifluoro-methylthio aniline raw material is difficult to prepare, and therefore it can only react with the indole reaction of electron rich
Limitation is bigger；Carbonylation, as Munavalli, S find under study for action, CF3Under SCl illumination can with trimethyl silicane
Base enol ether generation radical reaction, generates2-Trifluoromethylthio Ketohexamethylene,2,2-two trifluoromethylthio Ketohexamethylene and2,6Two or three
Fluorine methyl mercapto Ketohexamethylene etc., but its generation product is the most single-minded, and CF3SCl is unstable, and toxicity is big.In view of above-mentioned arylation, alkene
There are following various limitation in the reaction such as change, carbonylation: material toxicity is big, raw material is unstable, severe reaction conditions, must be with purple
Outer lamp or illumination could participate in reaction and substrate spectrum adaptability is the most extensive etc., and the present invention uses trifluoromethylthio
The method that this active fragment is grafted onto on indanone compounds is a series of with trifluoromethylthio indone class compound to prepare.
Summary of the invention
In order to overcome the deficiencies in the prior art, the invention provides a kind of environmental protection, prepare a kind of band safely and efficiently
The preparation method of the indanone compounds of trifluoromethylthio, this preparation method solves during directly generating indanone compounds
The technical barrier of the high cost existed and substrate bad adaptability etc.；And this preparation method has low cost, stability height, reaction
The plurality of advantages such as mild condition, the response time is short, cheaper starting materials is easy to get, product yield and purity are high.
To achieve these goals, the technical solution used in the present invention is: the indone class chemical combination of a kind of band trifluoromethylthio
The preparation method of thing, it is characterised in that comprise the following steps: choose acetylenic ketone compounds and fluoroform sulfane alcohol silver compound is
Raw material, using persulfate reagent as oxidant, with HMPA as stabilizer, in reaction dissolvent, in reaction temperature
Degree is 80oReact under C, react 12h, react the indanone compounds obtaining following formula (II) after terminating through post processing, its
Chemical equation is as follows,
(I) (II)
R in described Formulas I1For any one in hydrogen, halogen radical, alkoxyl.
Above-mentioned reaction temperature can be non-exclusively 40oC、50oC、60oC、70oC、80oC、90oC、100oC or 120oC, excellent
Choosing is 80 DEG C；Response time can be that 10 hours, 12 hours, 14 hours, 16 hours, 18 hours or 24 are little in non-limiting manner
Time, preferably 12h, or the response time can also be how many and true by the residual quantity of gas chromatograph-mass spectrometer or TLC detection raw material
The fixed suitable response time；Above-mentioned halogen similar nature, can select in-F ,-Cl ,-Br ,-I any one；And alkoxyl
Then can select CH3O-、C2H5O-、C3H7O-、C4H9O-、C5H11O-、C6H13Any one in the saturated alkoxyl of O-etc..
Further, any one during described persulfate reagent is potassium peroxydisulfate, sodium peroxydisulfate.
Further, described reaction dissolvent is acetonitrile, DMF (DMF), ethanol, dimethyl sulfoxide
(DMSO), in ethanol, acetone at least any one.It is preferably dimethyl sulfoxide.
Further, the mol ratio of described acetylenic ketone compounds and fluoroform sulfane alcohol silver compound is 1:1.5.Non-limiting
Property ground can be 1:1,1:1.2,1:1.5,1:1.8 or 1:2.0, preferably 1:1.5.
Further, the mol ratio of described acetylenic ketone compounds and HMPA stabilizer is 1:0.1.
Further, described acetylenic ketone compounds is 1:1-5 with the mol ratio of persulfate.Can be 1 in non-limiting manner:
1,1:2,1:3,1:4 or 1:5, both preferred mol ratios are 1:3-5.
Further, the post processing after reaction terminates comprises the steps, after completion of the reaction, with Rotary Evaporators from reaction
Removing solvent in the mixture obtained after end, residue 300-400 mesh silica gel column chromatography purifies and obtains target product, post layer
Analysis process can determine suitable eluting terminal with TLC tracing and monitoring.
Another object of the present invention is to provide a kind of by the band trifluoromethylthio obtained by above-mentioned preparation method
Indanone compounds, it is characterised in that comprise-SCF3Functional group, chemical structural formula is as follows:
R2For hydrogen.Wherein, R2Can also is that alkyl, alkoxyl, halogen radical etc..
Using such scheme, the synthetic method of the present invention is with acetylenic ketone compounds and fluoroform sulfane alcohol silver compound
(AgSCF3Owing to its stability is high, economical and easily available, it is to provide the ideal chose of trifluoromethylthio) it is raw material, use potassium peroxydisulfate
Or sodium peroxydisulfate reagent as oxidant and rotates suitable technological parameter and suitably combines, produced by persulfate
Free radical makes monovalence silver be oxidized to bivalence silver, thus produces trifluoromethylthio free radical, and cyclisation disappears through β-H further
Remove, thus a step has obtained the indanone compounds of band trifluoromethylthio；In this reaction system, raw material converts completely, only generates
Target product, does not has a generation of other impurity, and Atom economy height, synthetic system low cost, reaction condition are simple and permissible
Directly carrying out in atmosphere, for operator, safety is high；React the last handling process after terminating except above-mentioned side
Method, it is also possible to use any one of crystallization, column chromatography purification, extraction to process means or the combination of multiple process means.Should
Preparation method has that reaction condition is gentle, the response time is short, cheaper starting materials is easy to get, product yield and the plurality of advantages such as purity is high,
Preparation for novel trifluoromethylthio spiro-heterocycle compound provides effective synthetic method, have good researching value and
Application prospect.The method of currently used one-step synthesis indanone compounds, its substrate applicability is poor, the most above-mentioned band electron deficiency
Benzene ring type compounds cannot be reacted, and therefore, is not particularly suited for preparation and is introduced directly in indanone compounds by trifluoromethylthio,
And owing to temperature is the highest, trifluoromethylthio the most easily aoxidizes, so causing productivity relatively low, present invention adds hexamethyl phosphinylidyne
Triamine is the stabilizer of trifluoromethylthio, and cooperation persulfate improves the productivity of the target product of synthesis, solution the most of the present invention
Determine the series technique difficult problem in current anamorphic zone trifluoromethylthio indanone compounds method.
Below in conjunction with specific embodiment, the invention will be further described.
Accompanying drawing explanation
Accompanying drawing 1 is product 5-methoxyl group-3-phenyl-2-in the specific embodiment of the invention one to five, embodiment ten to ten three
((trifluoromethyl) sulfur)-1H-1-Indanone nuclear magnetic spectrogram；
Accompanying drawing 2 is product 5-methoxyl group-3-phenyl-2-((three in the specific embodiment of the invention one to five, embodiment ten to ten three
Methyl fluoride) sulfur)-1H-1-Indanone nuclear magnetic spectrogram；
Accompanying drawing 3 is product 5-methoxyl group-3-phenyl-2-((three in the specific embodiment of the invention one to five, embodiment ten to ten three
Methyl fluoride) sulfur)-1H-1-Indanone nuclear magnetic spectrogram；
Accompanying drawing 4 is product 7-chloro-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone core in the specific embodiment of the invention six
Magnetic spectrum figure；
Accompanying drawing 5 is product 7-chloro-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone core in the specific embodiment of the invention six
Magnetic spectrum figure；
Accompanying drawing 6 is product 7-chloro-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone core in the specific embodiment of the invention six
Magnetic spectrum figure；
Accompanying drawing 7 is product 3-phenyl-2-in the specific embodiment of the invention seven ((trifluoromethyl) sulfur)-1H-1-Indanone nuclear-magnetism spectrum
Figure；
Accompanying drawing 8 is product 3-phenyl-2-in the specific embodiment of the invention seven ((trifluoromethyl) sulfur)-1H-1-Indanone nuclear-magnetism spectrum
Figure；
Accompanying drawing 9 is product 3-phenyl-2-in the specific embodiment of the invention seven ((trifluoromethyl) sulfur)-1H-1-Indanone nuclear-magnetism spectrum
Figure；
Accompanying drawing 10 is product 5-ethyoxyl-3-phenyl-2-(trifluoromethyl) sulfur in the specific embodiment of the invention eight)-1H-indenes-1-
The nuclear magnetic spectrogram of ketone；
Accompanying drawing 11 is product 5-ethyoxyl-3-phenyl-2-(trifluoromethyl) sulfur in the specific embodiment of the invention eight)-1H-indenes-1-
The nuclear magnetic spectrogram of ketone；
Accompanying drawing 12 is product 5-ethyoxyl-3-phenyl-2-(trifluoromethyl) sulfur in the specific embodiment of the invention eight)-1H-indenes-1-
The nuclear magnetic spectrogram of ketone；
Accompanying drawing 13 is product 5,7-dimethoxy-3-benzene-2-(trifluoromethyl) sulfur in the specific embodiment of the invention nine)-1H-indenes-
1-ketone nuclear magnetic spectrogram；
Accompanying drawing 14 is product 5,7-dimethoxy-3-benzene-2-(trifluoromethyl) sulfur in the specific embodiment of the invention nine)-1H-indenes-
1-ketone nuclear magnetic spectrogram；
Accompanying drawing 15 is product 5,7-dimethoxy-3-benzene-2-(trifluoromethyl) sulfur in the specific embodiment of the invention nine)-1H-indenes-
1-ketone nuclear magnetic spectrogram.
Detailed description of the invention
The present invention is not limited to above-mentioned detailed description of the invention, and persons skilled in the art are according to disclosed by the invention interior
Hold, other multiple detailed description of the invention can be used to implement the present invention, or the design structure of every employing present invention and think of
Road, does simple change or change, both falls within protection scope of the present invention.
The specific embodiment of the present invention is as follows:
This course of reaction is as follows: choosing acetylenic ketone compounds A and fluoroform sulfane alcohol silver compound B is raw material, with persulfate
Reagent is as oxidant, with HMPA (HMPA) as stabilizer, in reaction dissolvent, is 80 in reaction temperatureoC
Under react, react 12h, reaction terminate after through post processing obtain indanone compounds.
Table 1-embodiment proportioning raw materials
Instantiation one: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver synthesis 5-
Methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:1:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 30%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H),
6.89-6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s)。
Instantiation two: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver to close
Become 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:2:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 53%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H),
6.89-6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s) 。
Instantiation three: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver to close
Become 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 82%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61-7.49 (m, 5H),
6.89-6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s) 。
Instantiation four: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver to close
Become 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:4:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 83%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61-7.49 (m, 5H),
6.89-6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s)。
Instantiation five: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver to close
Become 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；By raw material A, raw material B, potassium peroxydisulfate, HMPA massages
You weigh for 1:1.5:5:0.1 by ratio, and wherein (A) compound is 0.1 mmol.Reaction solution uses DMSO, reaction system is existed
80oStirring reaction 12 hours under C.Reaction cools down after terminating, and washes with saturated sodium-chloride water solution and is carried out, and anhydrous sodium sulfate removes
Water, short silicagel column sucking filtration, filtrate rotation steaming, removing potassium peroxydisulfate, removing solvent, residue silica gel column chromatography, petroleum ether drip washing,
TLC detects, and merges the effluent containing product, and Rotary Evaporators is distilled off solvent, and vacuum drying obtains the target of brown color
Product, productivity 80%, purity is 99.1%(HPLC).NMR (Nuclear Magnetic Resonance) spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d,J = 8.0 Hz, 1H), 7.61-7.49 (m, 5H), 6.89-6.69 (m, 2H), 3.85 (s, 3H).13C NMR
(125 MHz, CDCl3) δ 190.51, 167.94, 164.54 , 145.84, 130.79,130.67,, 128.79,
128.73 (q,J =308,1C,SCF3),128.53, 125.86 , 123.20, 119.42, 112.37, 112.13,
55.93.19F NMR (471 MHz, CDCl3) δ -40.11 (s) 。
Above-described embodiment one to five, R1During for methoxyl group, i.e. with use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-
1-ketone and fluoroform sulfane alcohol silver synthesis 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；Wherein variable
For the mol ratio of acetylenic ketone compounds Yu persulfate, wherein, when mol ratio is 1:3-5, productivity reaches more than 80%, explanation
Mol ratio between the two has material impact effect to productivity.
Specific embodiment six: R1During for chlorine, i.e. use 1-(2-chlorphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfur
Alkanol silver synthesis 7-chloro-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 78%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.56 (d, J = 4.2 Hz, 5H), 7.41-7.31 (m, 2H), 7.15
(d, J = 6.9 Hz, 1H).13C NMR (125 MHz, CDCl3) δ 188.32, 167.30, 144.96, 133.85,
132.40, 131.76, 130.54, 129.80 ,128.38, 128.13(q,J =308,1C,SCF3), 128.03 ,
125.56, 121.26, 118.46. 19F NMR (471 MHz, CDCl3) δ -39.83 (s) 。
Instantiation seven: R1During for H, i.e. use 1,3-hexichol-2-propargyl-1-ketone and fluoroform sulfane alcohol silver synthesis 3-
Phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, sodium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 77%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.69-7.65 (m, 1H), 7.62-7.55 (m, 5H), 7.49-7.40
(m, 2H), 7.26-7.22 (m, 1H) 19F NMR (471 MHz, CDCl3) δ -40.24 (s).13C NMR (125
MHz, CDCl3) δ 190.97, 168.96, 142.35, 132.73, 129.94, 129.88, 129.72, 129.70,
, 127.77 (s), 128.73 (q,J =308,1C,SCF3), 127.48, 122.79, 122.10, 116.86.19F
NMR (471 MHz, CDCl3) δ -40.24 (s) 。
Instantiation eight: R1During for ethyoxyl, i.e. use 1-(4-ethyoxyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform
Sulfane alcohol silver synthesis 5-ethyoxyl-3-phenyl-2-(trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 85%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.46 (s, 5H), 7.34-7.25 (m, 1H), 6.90 (d, J = 8.6
Hz, 1H), 6.73 (d, J = 7.2 Hz, 1H), 4.20 (q, J = 7.0 Hz, 2H), 1.43 (t, J = 7.0
Hz, 3H).13C NMR (125 MHz, CDCl3) δ 188.37, 166.49, 155.67, 144.57 , 134.53,
129.47, 128.99, 127.75(q,J =308,1C,SCF3),127.62, 117.52, 116.31, 115.29,
114.68, 63.98, 13.70. 19F NMR (471 MHz, CDCl3) δ -40.06 (s) 。
Above-described embodiment three, six to eight, raw material A, raw material B, potassium peroxydisulfate, the proportioning between HMPA is 1 the most in molar ratio:
1.5:3:0.1, and the R in raw material A1It is respectively adopted hydrogen, halogen radical, alkoxyl, and its productivity is relatively stable, illustrates this
Bright substrate has good adaptability.
Instantiation nine: 1-(2,4-dimethoxy benzene)-3-phenylpropyl alcohol-2-alkynes-1-ketone and fluoroform sulfane alcohol silver synthesis 5,
7-dimethoxy-3-benzene-2-(trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 86%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.58 – 7.48 (m, 5H), 6.38 (dd, J = 15.0, 1.8 Hz,
2H), 3.99 (s, 3H), 3.85 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 188.01, 166.39,
165.65, 159.13, 147.44, 130.87, 130.38, 128.73(q,J =308,1C,SCF3),128.66,
120.07, 108.87, 105.50, 98.58, 56.32, 55.98. 19F NMR (471 MHz, CDCl3) δ -39.99
(s) 。
Instantiation ten: R1During for methoxyl group, i.e. use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and three
Fluorine first sulfane alcohol silver synthesis 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses ethanol, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 30%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H),
6.89 – 6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s) 。
Instantiation 11: R1During for methoxyl group, use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and three
Fluorine first sulfane alcohol silver synthesis 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses CH3CN, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 57%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H),
6.89 – 6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s) 。
Instantiation 12: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver
Synthesis 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses DMF, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, and uses saturated chlorine
Change sodium water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes molten
Agent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators distills
Removing solvent, vacuum drying obtains the target product of brown color, productivity 45%, and purity is 99.1%(HPLC).NMR (Nuclear Magnetic Resonance) spectrum
:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H), 6.89
– 6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94, 164.54
, 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53, 125.86 ,
123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -40.11 (s) 。
Instantiation 13: use 1-(4-methoxyphenyl)-3-phenyl acrylate-2-alkynes-1-ketone and fluoroform sulfane alcohol silver
Synthesis 5-methoxyl group-3-phenyl-2-((trifluoromethyl) sulfur)-1H-1-Indanone；
By raw material A, raw material B, potassium peroxydisulfate, HMPA weighs for 1:1.5:3:0.1 in molar ratio, and wherein (A) compound is 0.1
mmol.Reaction solution uses acetone, by reaction system 80oStirring reaction 12 hours under C.Reaction cools down after terminating, with saturated
Sodium-chloride water solution is washed and is carried out, and anhydrous sodium sulfate removes water, short silicagel column sucking filtration, and filtrate rotation is steamed, and removes potassium peroxydisulfate, removes
Solvent, residue silica gel column chromatography, petroleum ether drip washing, TLC detects, and merges the effluent containing product, and Rotary Evaporators steams
Evaporating removing solvent, vacuum drying obtains the target product of brown color, productivity 15%, and purity is 99.1%(HPLC).Nuclear magnetic resonance, NMR ripple
Spectrum:1H NMR (500 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.61 – 7.49 (m, 5H),
6.89 – 6.69 (m, 2H), 3.85 (s, 3H).13C NMR (125 MHz, CDCl3) δ 190.51, 167.94,
164.54 , 145.84, 130.79,130.67,, 128.79, 128.73 (q,J =308,1C,SCF3),128.53,
125.86 , 123.20, 119.42, 112.37, 112.13, 55.93.19F NMR (471 MHz, CDCl3) δ -
40.11 (s) 。
Above-described embodiment ten-ten three understands with embodiment three contrast, raw material A, raw material B, potassium peroxydisulfate, joining between HMPA
It is 1:1.5:3:0.1 than the most in molar ratio, and the R in raw material A1All using methoxyl group, its variable is then to choose different reactions
Solvent, from above-described embodiment, the selection of solvent has significant impact to productivity, even if the solvent that some performances are similar, as
DMF and DMSO, it has different results to the productivity of the present invention, therefore the solvent of the present invention selects to be to create based on technical staff
Draw on the experiment basis of property, not there is universality, only there is adaptitude.
Claims (8)
1. the preparation method of the indanone compounds of a band trifluoromethylthio, it is characterised in that comprise the following steps: choose alkynes
Ketone compounds and fluoroform sulfane alcohol silver compound are raw material, using persulfate reagent as oxidant, with hexamethyl phosphinylidyne
Triamine is stabilizer, in reaction dissolvent, is 80 in reaction temperatureoReact under C, react 12h, reaction terminate after through after
Processing the indanone compounds obtaining following formula (II), its chemical equation is as follows,
(I) (II)
R in described Formulas I1For any one in hydrogen, halogen radical, alkoxyl.
The preparation method of the indanone compounds of band trifluoromethylthio the most according to claim 1, it is characterised in that: described
Persulfate reagent is any one in potassium peroxydisulfate, sodium peroxydisulfate.
The preparation method of the indanone compounds of band trifluoromethylthio the most according to claim 1, it is characterised in that: described
Reaction dissolvent is the most any one in acetonitrile, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethanol, acetone
Kind.
4., according to the preparation method of the indanone compounds of the band trifluoromethylthio described in claim 1-3 any one, it is special
Levy and be: the mol ratio of described acetylenic ketone compounds and fluoroform sulfane alcohol silver compound is 1:1.5.
5., according to the preparation method of the indanone compounds of the band trifluoromethylthio described in claim 1-3 any one, it is special
Levy and be: the mol ratio of described acetylenic ketone compounds and HMPA stabilizer is 1:0.1.
6., according to the preparation method of the indanone compounds of the band trifluoromethylthio described in claim 1-4 any one, it is special
Levy and be: described acetylenic ketone compounds is 1:1-5 with the mol ratio of persulfate.
The preparation method of the indanone compounds of band trifluoromethylthio the most according to claim 1, it is characterised in that: reaction
Post processing after end comprises the steps, after completion of the reaction, with Rotary Evaporators after reaction terminates the mixture that obtains
Removing solvent, residue 300-400 mesh silica gel column chromatography purifies and obtains target product, and column chromatography procedure can be followed the tracks of with TLC
Monitor and determine suitable eluting terminal.
8. an indanone compounds for the band trifluoromethylthio obtained by the preparation method as described in claim 1-7, it is special
Levy and be, comprise-SCF3Functional group, chemical structural formula is as follows:
R2For hydrogen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610547078.4A CN106187840B (en) | 2016-07-08 | 2016-07-08 | A kind of indanone compounds with trifluoromethylthio and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610547078.4A CN106187840B (en) | 2016-07-08 | 2016-07-08 | A kind of indanone compounds with trifluoromethylthio and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106187840A true CN106187840A (en) | 2016-12-07 |
| CN106187840B CN106187840B (en) | 2017-10-10 |
Family
ID=57477784
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610547078.4A Expired - Fee Related CN106187840B (en) | 2016-07-08 | 2016-07-08 | A kind of indanone compounds with trifluoromethylthio and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106187840B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989035A (en) * | 2022-07-08 | 2022-09-02 | 扬州工业职业技术学院 | Sulfuryl fluoride promoted reaction method for converting beta-diketone to alkyne |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804348A (en) * | 2012-11-15 | 2014-05-21 | 中国科学院上海有机化学研究所 | Electrophilic fluoroform sulfenyl reagent and synthetic method and application thereof |
| CN104945294A (en) * | 2014-03-31 | 2015-09-30 | 中国科学院上海有机化学研究所 | Compound containing trifluoromethylthio group and preparation method thereof |
-
2016
- 2016-07-08 CN CN201610547078.4A patent/CN106187840B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804348A (en) * | 2012-11-15 | 2014-05-21 | 中国科学院上海有机化学研究所 | Electrophilic fluoroform sulfenyl reagent and synthetic method and application thereof |
| CN104945294A (en) * | 2014-03-31 | 2015-09-30 | 中国科学院上海有机化学研究所 | Compound containing trifluoromethylthio group and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| SHAO, XINXIN 等: "An Electrophilic Hypervalent Iodine Reagent for Trifluoromethylthiolation", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989035A (en) * | 2022-07-08 | 2022-09-02 | 扬州工业职业技术学院 | Sulfuryl fluoride promoted reaction method for converting beta-diketone to alkyne |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106187840B (en) | 2017-10-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5455916B2 (en) | Method for continuously producing 3-isothiazolinone derivatives and intermediate products thereof | |
| CN107488139B (en) | Preparation method of sulfur-containing 3-arylmethylene isoindolinone derivative | |
| CN105859664A (en) | Firocoxib preparation method | |
| CN105801575A (en) | Synthetic method of imidazo[1,2-a]pyridine | |
| CN110078737A (en) | Perfluoroalkyl substituted benzimidazole and compound of isobioquin group and preparation method thereof | |
| CN106187840A (en) | A kind of indanone compounds of band trifluoromethylthio and preparation method thereof | |
| FI91638C (en) | Process for the preparation of tetracyclic antidepressants | |
| CN104610267B (en) | Method for efficiently synthesizing 6-alkyl pyrazolo [1,5-c ] quinazoline framework compound under non-catalytic condition | |
| Burgess et al. | Dimerization of glycine derivatives | |
| CN108610275A (en) | A kind of synthetic method of 3- (2- vinyls) indole derivatives | |
| CN110078766A (en) | Phosphonylation benzimidazole and compound of isobioquin group and preparation method thereof | |
| CN106256818B (en) | A kind of indone with trifluoromethylthio and its derivative and preparation method thereof | |
| CN105884739B (en) | A kind of synthetic method of benzo cumarin polycyclic compound | |
| Chengfei et al. | Synthesis, herbicidal activity and three-dimensional quantitative structure-activity relationship (3D-QSAR) study of 4-methyl-1, 2, 4-triazole-thioether compounds containing natural styrene structure | |
| CN105693778B (en) | The method of N- methoxymethylamide guiding synthesis ferrocene and Pyridione derivatives | |
| CN108690018B (en) | Preparation method of imidazo [1,2-a ] pyridine derivative | |
| CN108047133A (en) | A kind of preparation method of quinolinones compound | |
| CN103965203B (en) | Imidazo-[1,2-c]-quinazolin-3(2H)-one fused-heterocycle compounds and preparation method thereof | |
| CN113200866A (en) | Synthetic method of diafenthiuron impurity D | |
| Lee et al. | Synthesis of 1, 3-oxazolidines by copper-catalyzed addition of acetone and ethyl diazoacetate to imines | |
| CN104140409A (en) | Efficient synthesis method of novel fluorescent material 1,3-dihydroisobenzofuran compound | |
| Koperniku et al. | The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides | |
| CN109134357A (en) | The method of the efficient high selectivity 2- amino -5- chloropyridine of one-step method | |
| CN104447557B (en) | A kind of preparation method of N arylpyrazoles compound and N aryl imidazoles | |
| Hay et al. | A regio-and stereocontrolled method for preparing 3, 3-diarylacrylamides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200922 Address after: 325000 No.167 Ningcheng West Road, Haibin street, Longwan District, Wenzhou City, Zhejiang Province Patentee after: Wenzhou prosess Testing Technology Co., Ltd Address before: 325000 Zhejiang, Ouhai, South East Road, No. 38, Wenzhou National University Science Park Incubator Patentee before: Wenzhou University |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171010 Termination date: 20210708 |