CN106187840B - A kind of indanone compounds with trifluoromethylthio and preparation method thereof - Google Patents
A kind of indanone compounds with trifluoromethylthio and preparation method thereof Download PDFInfo
- Publication number
- CN106187840B CN106187840B CN201610547078.4A CN201610547078A CN106187840B CN 106187840 B CN106187840 B CN 106187840B CN 201610547078 A CN201610547078 A CN 201610547078A CN 106187840 B CN106187840 B CN 106187840B
- 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.)
- Expired - Fee Related
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 a kind of preparation method of the indanone compounds with trifluoromethylthio, this method chooses acetylenic ketone compounds and fluoroform sulfane alcohol silver compound is raw material, oxidant is used as using persulfate reagent, using HMPA as stabilizer, in reaction dissolvent, in reaction temperature be 80oReacted under C, react 12h, reaction obtains indanone compounds after terminating through post processing, the preparation method, which is solved, solves the technical barrier that amide-type and heterocycle directly generate indanone compounds, and the preparation method have it is economical save money, stability is high, reaction condition is gentle, the reaction time is short, raw material is cheap and easy to get, product yield and many advantages, such as high purity.
Description
Technical field
The invention belongs to organic chemical synthesis technical field, be related to a kind of indanone compounds with trifluoromethylthio and its
Preparation method.
Background technology
Trifluoromethylthio (- SCF3) has strong sucting electronic effect, highly lipophilic（Hydrophobic Parameters）With it is good
The characteristic such as bioactivity, therefore compound chemical stability and metabolism can be significantly changed by being introduced into organic compound
Stability.Therefore ,-SCF is contained3The compound of base is in medicine, and the field such as agricultural chemicals and material has greatly potential answer
With value.For example, Coccidiostatic Drug Toltrazuril（Toltrazuril）, insecticide (Vaniliprole) and anorexia medicine
Thing Tiflorex (Tiflorex), antihypertensive Losartan (Losartan analogue) etc., all containing fluoroform sulphur
Base, shown in following article chemical structural formula：
Good characteristic based on trifluoromethylthio, people show extensive interest to trifluoromethylthioization reaction.For example,
Researcher, which has researched and developed, is prepared for a variety of arylations, alkylene, and carbonylation etc. carries the related compound of trifluoromethylthio.
The trifluoro methyl mercaptan CF that arylation reaction, such as Harris are found3Addition reactions of the SH to fluoroolefins, the reaction is in X
Then ray or the lower generation trifluoromethylthio free radical of ultraviolet irradiation carry out addition to fluoroolefins.But it is difficult to there is raw material in the reaction
To preserve, the shortcomings of reaction condition is more harsh；As Billard is usedN-The indoles of trifluoro-methylthio aniline and electron rich is to first
Occur electrophilic reaction in the presence of benzene sulfonic acid and solvent DCM, carry out olefination, the indoles of generation trifluoromethylthio substitution
Compound；But but due toN-Trifluoro-methylthio aniline raw material is difficult to prepare, and the indole reaction that it can only be with electron rich, therefore reaction
Limitation is larger；Carbonylation, such as Munavalli, S has found under study for action, CF3Under SCl illumination can with trimethyl silicane
Radical reaction, generation occur for base enol ether2-Trifluoromethylthio cyclohexanone,2,2- two trifluoromethylthio cyclohexanone and2,6Two or three
Fluorine methyl mercapto cyclohexanone etc., but its generation product is not single-minded, and CF3SCl is unstable, and toxicity is big.In view of above-mentioned arylation, alkene
There is following various limitations in the reactions such as change, carbonylation：Material toxicity is big, raw material is unstable, severe reaction conditions, must with purple
Outer lamp or illumination could be participated in reacting and substrate spectrum adaptability is not extensive etc., and the present invention is used trifluoromethylthio
It is a series of with trifluoromethylthio indone class compound to prepare that this active fragment is grafted onto the method on indanone compounds.
The content of the invention
In order to overcome the deficiencies in the prior art, the invention provides a kind of environmental protection, a kind of band is safely and efficiently prepared
The preparation method of the indanone compounds of trifluoromethylthio, the preparation method is solved directly generate indanone compounds during
The too high technical barrier with substrate bad adaptability etc. of cost of presence；And the preparation method has that cost is low, stability is high, reaction
Mild condition, the reaction time is short, raw material is cheap and easy to get, product yield and many advantages, such as high purity.
To achieve these goals, the technical solution adopted by the present invention is：A kind of indone class chemical combination with 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, using HMPA as stabilizer, in reaction dissolvent, in reaction temperature
Spend for 80oReacted under C, react 12h, reaction obtains such as following formula after terminating through post processing（II）Indanone compounds, its
Chemical equation is as follows,
（I） (II）
R in the Formulas I1For any one in hydrogen, halogen radical, alkoxy.
Above-mentioned reaction temperature can be non-exclusively 40oC、50oC、60oC、70oC、80oC、90oC、100oC or 120oC, it is excellent
Choosing is 80 DEG C；Reaction time in non-limiting manner can be small for 10 hours, 12 hours, 14 hours, 16 hours, 18 hours or 24
When, preferably 12h, or reaction time can also detect the residual quantity of raw material is how many and true by gas chromatograph-mass spectrometer or TLC
The fixed suitable reaction time；Above-mentioned halogen similar nature, can select any one in-F ,-Cl ,-Br ,-I；And alkoxy
CH can then be selected3O-、C2H5O-、C3H7O-、C4H9O-、C5H11O-、C6H13Any one in O- etc. saturation alkoxies.
Further, the persulfate reagent is any one in potassium peroxydisulfate, sodium peroxydisulfate.
Further, the reaction dissolvent is acetonitrile, DMF（DMF）, ethanol, dimethyl sulfoxide (DMSO)
（DMSO）, ethanol, in acetone at least any one.Preferably dimethyl sulfoxide (DMSO).
Further, the acetylenic ketone compounds and the mol ratio of fluoroform sulfane alcohol silver compound are 1:1.5.It is non-limiting
Property can be 1:1、1:1.2、1:1.5、1:1.8 or 1:2.0, preferably 1:1.5.
Further, the acetylenic ketone compounds and the mol ratio of HMPA stabilizer are 1:0.1.
Further, the acetylenic ketone compounds and the mol ratio of persulfate are 1:1-5.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 following steps, after completion of the reaction, with Rotary Evaporators from reaction
Solvent is removed in the mixture obtained after end, residue obtains target product, post layer with the purification of 300-400 mesh silica gel column chromatography
Analysis process can determine suitably to elute terminal with TLC tracing and monitorings.
Another object of the present invention is to provide it is a kind of as obtained by above-mentioned preparation method with trifluoromethylthio
Indanone compounds, it is characterised in that comprising-SCF3Functional group, chemical structural formula is as follows：
R2For hydrogen.Wherein, R2It can also be alkyl, alkoxy, halogen radical etc..
Using such scheme, synthetic method of the invention is with acetylenic ketone compounds and fluoroform sulfane alcohol silver compound
（AgSCF3Because its stability is high, economical and easily available, it is to provide the ideal chose of trifluoromethylthio）For raw material, potassium peroxydisulfate is used
Or sodium peroxydisulfate reagent is suitably combined as oxidant and the suitable technological parameter of rotation, is produced by persulfate
Free radical causes monovalence silver to be oxidized to divalence silver, so as to produce trifluoromethylthio free radical, further cyclisation disappears by β-H
Remove, so that a step has obtained the indanone compounds with trifluoromethylthio；In the reaction system, raw material is converted completely, is only generated
Target product, the generation without other impurities, Atom economy is high, synthetic system cost is low, reaction condition is simple, and can be with
Directly carry out in atmosphere, it is safe for operating personnel；The last handling process after terminating is reacted except above-mentioned side
Method, can also use the combination of any one of crystallization, column chromatography purification, extraction processing means or a variety of processing means.Should
Preparation method has that reaction condition is gentle, the reaction time is short, raw material is cheap and easy to get, product yield and many advantages, such as high purity,
Preparation for new trifluoromethylthio spiro-heterocycle compound provides effective synthetic method, with good researching value and
Application prospect.At present using the method for one-step synthesis indanone compounds, its substrate applicability is poor, than band electron deficient as described above
Benzene ring type compounds cannot react, therefore, be not particularly suited for preparation and trifluoromethylthio is introduced directly into indanone compounds,
And because temperature is higher, the easier oxidation of trifluoromethylthio, so causing yield relatively low, present invention adds hexamethyl phosphinylidyne
Triamine is the stabilizer of trifluoromethylthio, coordinates persulfate to improve the yield of the target product of synthesis, therefore present invention solution
Series technique problem in current anamorphic zone trifluoromethylthio indanone compounds method of having determined.
With reference to specific embodiment, the invention will be further described.
Brief description of the drawings
Accompanying drawing 1 is product 5- methoxyl group -3- phenyl -2- in the specific embodiment of the invention one to five, embodiment ten to 13
((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear magnetic spectrograms；
Accompanying drawing 2 is product 5- methoxyl group -3- phenyl -2- in the specific embodiment of the invention one to five, embodiment ten to 13
((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear magnetic spectrograms；
Accompanying drawing 3 is product 5- methoxyl group -3- phenyl -2- in the specific embodiment of the invention one to five, embodiment ten to 13
((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear magnetic spectrograms；
Accompanying drawing 4 is the chloro- 3- phenyl -2- of product 7- ((trifluoromethyl) sulphur) -1H- indenes -1- in the specific embodiment of the invention six
Ketone nuclear magnetic spectrogram；
Accompanying drawing 5 is the chloro- 3- phenyl -2- of product 7- ((trifluoromethyl) sulphur) -1H- indenes -1- in the specific embodiment of the invention six
Ketone nuclear magnetic spectrogram；
Accompanying drawing 6 is the chloro- 3- phenyl -2- of product 7- ((trifluoromethyl) sulphur) -1H- indenes -1- in the specific embodiment of the invention six
Ketone nuclear magnetic spectrogram；
Accompanying drawing 7 is product 3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear-magnetisms in the specific embodiment of the invention seven
Spectrogram；
Accompanying drawing 8 is product 3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear-magnetisms in the specific embodiment of the invention seven
Spectrogram；
Accompanying drawing 9 is product 3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanone nuclear-magnetisms in the specific embodiment of the invention seven
Spectrogram；
Accompanying drawing 10 is product 5- ethyoxyl -3- phenyl -2- (trifluoromethyl) sulphur in the specific embodiment of the invention eight) -1H-
The nuclear magnetic spectrogram of 1-Indanone；
Accompanying drawing 11 is product 5- ethyoxyl -3- phenyl -2- (trifluoromethyl) sulphur in the specific embodiment of the invention eight) -1H-
The nuclear magnetic spectrogram of 1-Indanone；
Accompanying drawing 12 is product 5- ethyoxyl -3- phenyl -2- (trifluoromethyl) sulphur in the specific embodiment of the invention eight) -1H-
The nuclear magnetic spectrogram of 1-Indanone；
Accompanying drawing 13 is product 5,7- dimethoxy -3- benzene -2- (trifluoromethyl) sulphur in the specific embodiment of the invention nine) -1H-
1-Indanone nuclear magnetic spectrogram；
Accompanying drawing 14 is product 5,7- dimethoxy -3- benzene -2- (trifluoromethyl) sulphur in the specific embodiment of the invention nine) -1H-
1-Indanone nuclear magnetic spectrogram；
Accompanying drawing 15 is product 5,7- dimethoxy -3- benzene -2- (trifluoromethyl) sulphur in the specific embodiment of the invention nine) -1H-
1-Indanone nuclear magnetic spectrogram.
Embodiment
The present invention is not limited to above-mentioned embodiment, and persons skilled in the art are according to disclosed by the invention interior
Hold, the present invention, or every design structure and think of using the present invention can be implemented using other a variety of embodiments
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：
The course of reaction is as follows：Selection acetylenic ketone compounds A and fluoroform sulfane alcohol silver compound B is raw material, with over cure
Silicate reagent is as oxidant, with HMPA (HMPA) for stabilizer, in reaction dissolvent, in reaction temperature be 80oReacted under C, react 12h, reaction obtains indanone compounds after terminating through post processing.
Table 1- embodiment raw material proportionings
Instantiation one：Closed using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Into 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:1:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 30%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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：Closed using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Into 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:2:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 53%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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：Closed using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Into 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 82%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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：Closed using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Into 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:4:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 83%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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：Closed using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Into 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；By raw material A, raw material B, potassium peroxydisulfate, HMPA massages
You are than being 1:1.5:5:0.1 weighs, wherein（A）Compound is 0.1 mmol.Reaction solution uses DMSO, and reaction system is existed
80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is washed and is cleaned with saturated sodium-chloride water solution, anhydrous sodium sulfate is removed
Water, short silicagel column suction filtration, filtrate revolving removes potassium peroxydisulfate, removes solvent, and residue silica gel column chromatography, petroleum ether is eluted,
TLC is detected, merges the efflux containing product, and solvent is distilled off in Rotary Evaporators, and vacuum drying obtains the target of brown color
Product, yield 80%, purity is 99.1%（HPLC）.NMR 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 using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -
1- ketone and fluoroform sulfane alcohol silver synthesis 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；Wherein variable
For acetylenic ketone compounds and the mol ratio of persulfate, wherein, when mol ratio is 1:During 3-5, yield reaches more than 80%, explanation
Mol ratio between the two has material impact effect to yield.
Specific embodiment six：R1During for chlorine, i.e., using 1- (2- chlorphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulphur
Alkanol silver synthesis 7- chloro- 3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 78%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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., using 1,3- hexichol -2- propargyl -1- ketone and fluoroform sulfane alcohol silver synthesis 3-
Phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, sodium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 77%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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., using 1- (4- ethyoxyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform
Sulfane alcohol silver synthesis 5- ethyoxyl -3- phenyl -2- (trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 85%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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) 。
Proportioning between above-described embodiment three, six to eight, raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:
1.5:3:0.1, and the R in raw material A1Hydrogen, halogen radical, alkoxy has been respectively adopted, and its yield is relatively stable, illustrates this hair
Bright substrate has good adaptability.
Instantiation nine：1- (2,4- dimethoxy benzenes) -3- phenylpropyl alcohol -2- alkynes -1- ketone and fluoroform sulfane alcohol silver synthesis 5,
7- dimethoxy -3- benzene -2- (trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMSO, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 86%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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., using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and three
Fluorine first sulfane alcohol silver synthesis 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses ethanol, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 30%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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, using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and three
Fluorine first sulfane alcohol silver synthesis 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses CH3CN, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 57%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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：Using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Synthesize 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses DMF, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, with full
Wash and cleaned with sodium-chloride water solution, anhydrous sodium sulfate water removal, short silicagel column suction filtration, filtrate revolving removes potassium peroxydisulfate, removed
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, Rotary Evaporators
Solvent is distilled off, vacuum drying obtains the target product of brown color, and yield 45%, purity is 99.1%（HPLC）.Nuclear magnetic resonance
Wave 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：Using 1- (4- methoxyphenyls) -3- phenyl propyl- 2- alkynes -1- ketone and fluoroform sulfane alcohol silver
Synthesize 5- methoxyl group -3- phenyl -2- ((trifluoromethyl) sulphur) -1H- 1-Indanones；
By raw material A, raw material B, potassium peroxydisulfate, HMPA is 1 in molar ratio:1.5:3:0.1 weighs, wherein（A）Compound is
0.1 mmol.Reaction solution uses acetone, by reaction system 80oStirring reaction 12 hours under C.Reaction is cooled down after terminating, and is used
Saturated sodium-chloride water solution, which is washed, to be cleaned, anhydrous sodium sulfate water removal, short silicagel column suction filtration, and filtrate revolving removes potassium peroxydisulfate,
Solvent is removed, residue silica gel column chromatography, petroleum ether elution, TLC detections merge the efflux containing product, rotary evaporation
Solvent is distilled off in instrument, and vacuum drying obtains the target product of brown color, and yield 15%, purity is 99.1%（HPLC）.Nuclear-magnetism is total to
Vibration wave is composed：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 is contrasted with embodiment three and understood, raw material A, raw material B, potassium peroxydisulfate, matching somebody with somebody between HMPA
Than being 1 in molar ratio:1.5:3:0.1, and the R in raw material A1Methoxyl group is used, its variable is then to choose different reactions
Solvent, from above-described embodiment, the selection of solvent has significant impact to yield, even if the similar solvent of some performances, such as
DMF and DMSO, it has different results to yield of the invention, therefore the solvent selection of the present invention is created based on technical staff
Property experiment basis on draw, without generality, only there is adaptitude.
Claims (7)
1. a kind of preparation method of the indanone compounds with 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, in reaction temperature be 80oReacted under C, react 12h, reacted after terminating after
Processing obtains such as following formula（II）Indanone compounds, its chemical equation is as follows,
（I） (II）
R in the Formulas I1For any one in hydrogen, halogen radical, alkoxy.
2. the preparation method of the indanone compounds according to claim 1 with trifluoromethylthio, it is characterised in that：It is described
Persulfate reagent is any one in potassium peroxydisulfate, sodium peroxydisulfate.
3. the preparation method of the indanone compounds according to claim 1 with trifluoromethylthio, it is characterised in that：It is described
Reaction dissolvent is acetonitrile, N,N-dimethylformamide（DMF）, dimethyl sulfoxide (DMSO)（DMSO）, it is ethanol, at least any one in acetone
Kind.
4. the preparation method of the indanone compounds with trifluoromethylthio according to claim 1-3 any one, it is special
Levy and be：The acetylenic ketone compounds and the mol ratio of fluoroform sulfane alcohol silver compound are 1:1.5.
5. the preparation method of the indanone compounds with trifluoromethylthio according to claim 1-3 any one, it is special
Levy and be：The acetylenic ketone compounds and the mol ratio of HMPA stabilizer are 1:0.1.
6. the preparation method of the indanone compounds with trifluoromethylthio according to claim 1-3 any one, it is special
Levy and be：The acetylenic ketone compounds and the mol ratio of persulfate are 1:1-5.
7. the preparation method of the indanone compounds according to claim 1 with trifluoromethylthio, it is characterised in that：Reaction
Post processing after end comprises the following steps, after completion of the reaction, with Rotary Evaporators from reaction terminate after in obtained mixture
Solvent is removed, residue obtains target product with the purification of 300-400 mesh silica gel column chromatography, and column chromatography procedure can be tracked with TLC
Monitor and determine suitable elution terminal.
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 CN106187840A (en) | 2016-12-07 |
| CN106187840B true 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) |
Families Citing this family (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 |
|---|
| An Electrophilic Hypervalent Iodine Reagent for Trifluoromethylthiolation;Shao, Xinxin 等;《Angewandte Chemie, International Edition》;20131231;第52卷(第12期);第3457-3460页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106187840A (en) | 2016-12-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPH11500753A (en) | Separation and purification of paclitaxel and cephalomannin | |
| CN107488139B (en) | Preparation method of sulfur-containing 3-arylmethylene isoindolinone derivative | |
| CN109320496B (en) | Selenocyanization reagent and preparation method and application thereof | |
| CN108117507A (en) | A kind of preparation method and use of azaspiro cyclohexadienone | |
| CN111108095B (en) | Method for preparing aryl sulfonyl acrylonitrile by photocatalysis | |
| CN104529896B (en) | Synthetic method of diaryl substituted isoquinoline compound | |
| CN106187840B (en) | A kind of indanone compounds with trifluoromethylthio and preparation method thereof | |
| Saikia et al. | Visible-light-promoted sulfenylation of 6-aminouracils under catalyst-free conditions | |
| Enders et al. | Asymmetric Synthesis of Thiadecalins via an Organocatalytic Triple Cascade/Sulfa-Michael Sequence | |
| CN106256818B (en) | A kind of indone with trifluoromethylthio and its derivative and preparation method thereof | |
| CN110511193A (en) | A kind of α -one thioamide analog compound and its synthetic method | |
| CN105884739B (en) | A kind of synthetic method of benzo cumarin polycyclic compound | |
| CN102219803A (en) | Preparation method of ezetimibe intermediate | |
| CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
| CN105693778B (en) | The method of N- methoxymethylamide guiding synthesis ferrocene and Pyridione derivatives | |
| CN108690018B (en) | Preparation method of imidazo [1,2-a ] pyridine derivative | |
| Koperniku et al. | The Reaction of N-Trimethylsilyl-Substituted Heteroarylamines with Esters and Thioesters: An Efficient Protocol To Access Diheteroarylamides | |
| CN107021968B (en) | The method of the polysubstituted organic photochemical catalyst catalyzing indole quinoline class compound oxidation dehydrogenation synthesis of indole class compound of BODIPY | |
| CN110563632B (en) | Electrophilic selenocyanization reagent and preparation method and application thereof | |
| CN105481806B (en) | The synthetic method of the 5-membered ring compounds containing sulfuryl and application | |
| CN105837544B (en) | A kind of organic nitrine synthesizes the new method of the ketones derivant of 3 amino chromene 2 with cumarin | |
| CN108047296A (en) | A kind of preparation method of betamethasone intermediate | |
| CN106632182A (en) | Preparation method of escitalopram oxalate demethylation impurity | |
| Syvret et al. | Selective fluorination of an aryl triazolinone herbicide intermediate | |
| CN106674050B (en) | A kind of synthetic method of benzophenone substituted isoquinoline compound |
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 |