CN106008136B - A kind of preparation method of 6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes - Google Patents
A kind of preparation method of 6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes Download PDFInfo
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- CN106008136B CN106008136B CN201610330861.5A CN201610330861A CN106008136B CN 106008136 B CN106008136 B CN 106008136B CN 201610330861 A CN201610330861 A CN 201610330861A CN 106008136 B CN106008136 B CN 106008136B
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- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/24—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by elimination of water
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- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
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- C07C29/36—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal
- C07C29/38—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones
- C07C29/40—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring increasing the number of carbon atoms by reactions with formation of hydroxy groups, which may occur via intermediates being derivatives of hydroxy, e.g. O-metal by reaction with aldehydes or ketones with compounds containing carbon-to-metal bonds
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Abstract
The invention discloses a kind of preparation methods of 6,6,12,12 tetramethyl 6,12 dihydro indeno [1,2 b] fluorenes.This method includes：Coupling reaction：O-dibromobenzene and 9,9 dimethyl fluorene, 2 boric acid carry out coupling reaction, compound shown in production M 1；Addition reaction：Then compound shown in formula M 1 first hydrolyzes, compound shown in production M 2 with butyl lithium reaction then with acetone progress addition reaction；Ring-closure reaction：Ring-closure reaction is carried out in the presence of idic acid shown in formula M 2, is converted into 6,6,12,12 tetramethyl, 6,12 dihydro indeno [1,2 b] fluorenes shown in formula M.
Description
Technical field
The invention belongs to organic synthesis field, more particularly to a kind of 6,6,12,12- tetramethyl -6,12- dihydro indenos [1,
2-b] fluorenes preparation method.
Background technology
6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes is a kind of organic material.6,6,12,12- tetramethyls
Base -6,12- dihydro indeno [1,2-b] fluorenes can prepare 2,8- bis- bromo- 6,6,12,12- tetramethyls -6,12- by bromo-reaction
Dihydro indeno [1,2-b] fluorenes, two bromine quilts of 2,8- bis- bromo- 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes
Diaryl-amine class compound replaces, and tri-arylamine group compound shown in formula (I) is prepared, can apply in organic electroluminescence device
In material.
In formula (I), work as Ar1Selected from phenyl, Ar2When selected from 1- naphthalenes, shown in structure such as formula (II), Kimura is true et al.
Triarylamine compounds shown in formula (II) are disclosed in CN101142170 as organic electroluminescence device hole mobile material
Using using shown in formula (II), compound is as the device of organic electroluminescence device hole mobile material, in brightness, efficiency side
Face shows more excellent performance.
In formula (I), work as Ar1Selected from 4- aminomethyl phenyls, Ar2When selected from 4- aminomethyl phenyls, shown in structure such as formula (III),
Philip Hurst Vista weber etc. discloses triarylamine compounds shown in formula (III) as organic electroluminescence in CN101228250
The application of luminescent device light emitting layer dopant is mixed using compound shown in formula (III) as organic electroluminescence device luminescent layer
The device of sundries shows more excellent performance in terms of chromaticity coordinates, brightness, efficiency.
Therefore, 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes are synthesized, and then are synthesized accordingly with formula
(I) compound of structure, the synthesis for electroluminescent organic material seem more important.
Currently, about 6, the preparation method of 6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes includes mainly such as
Lower two kinds：
The first is true et al. the preparation method disclosed in CN101142170 of Kimura, the chemical reaction equation of this method
Formula is as follows：
In the method, SUZUKI coupling reactions, system are carried out using 2,5- dibromoterephthalic acids dimethyl ester and phenyl boric acid
Standby intermediate 1, yield 80%；Intermediate 1 prepares intermediate 2, yield 70% in 80% sulfuric acid, in 180 DEG C of cyclization；It is intermediate
For body 2 in diethylene glycol (DEG) under the conditions of 200 DEG C, hydrazine hydrate reduction obtains intermediate 3, yield 50%；Intermediate 3 is in dimethyl sulfoxide
In, potassium tert-butoxide is alkali and iodomethane carries out substitution reaction, and mesh is prepared in the crude product being prepared column chromatography exquisiteness
Mark product 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes, yield 95%.This preparation method needs four steps anti-
It answers, overall yield of reaction 26.6%, and the reaction temperature of intermediate 2 and intermediate 3 is higher, not easy to operate, final products 6,6,
12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes are needed through pillar layer separation, cumbersome.
Second is Van Chung Pham etc. in Bull.Korean Chem.Soc.2011, Vol.32, No.51781~
The chemical equation of preparation method disclosed in 1783, this method is as follows：
In the method, intermediate 4 is prepared using 2,5- dibromos paraxylene and phenyl boric acid coupling reaction, then uses Gao Meng
Sour potassium oxidation, obtains intermediate 5, this two-step reaction yield 92%；Then 5 priority of intermediate and the reaction of thionyl chloride and methanol,
Intermediate 6, yield 100% are prepared, intermediate 6 and methyl-magnesium-bromide carry out addition reaction, then hydrolyze, prepare intermediate 7, receive
Rate 96%；Intermediate 7 in methylene chloride, is added concentrated hydrochloric acid reflux, obtains 6,6,12,12- tetramethyl -6,12- of target product
Dihydro indeno [1,2-b] fluorenes, yield 80%.This preparation method needs the reaction of 5 steps, total recovery 70.65%.The method and Kimura are true
Et al. the preparation method disclosed in CN101142170 compare, yield has significant raising, but still remains many lack
Point.During preparing intermediate 5 by intermediate 4 first, the potassium permanganate oxidation for using 12 equivalents, reaction is needed to generate more
Solid waste, processing are difficult；Secondly it during intermediate 5 prepares intermediate 6, needs to use the protochloride easily hydrolyzed
Sulfone increases operation difficulty, brings inconvenience to batch production；Third is preparing target product 6,6,12,12- tetra- by intermediate 7
In the reaction of methyl -6,12- dihydro indeno [1,2-b] fluorenes, need in methylene chloride, concentrated hydrochloric acid reflux, batch production to be added
When, volatile hydrogen chloride gas in hydrochloric acid is easy to pollute production environment, and it is possible to corrode production equipment.
Invention content
The present invention provides a kind of preparation method of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes, solutions
Harsh, the cumbersome and low yield technical problem of condition existing in the prior art of having determined.
According to an aspect of the present invention, a kind of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes are provided
Preparation method, this method includes：
Coupling reaction：With the o-dibromobenzene of 1 equivalent and 9, the 9- dimethyl fluorene -2- boric acid of 1~1.4 equivalent be coupled anti-
It answers, compound shown in production M-1；
Addition reaction：Compound shown in formula M-1 is first reacted with the butyl lithium of 1~1.5 equivalent, then with the third of 1~2 equivalent
Ketone carries out addition reaction, then hydrolyzes, compound shown in production M-2；
Ring-closure reaction：Compound shown in formula M-2 carries out ring-closure reaction in the presence of the acid of 3~16 equivalents, is converted into formula M institutes
6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes shown；
Optionally, preparation in accordance with the present invention, in the ring-closure reaction, the acid is selected from Loprazolam, trifluoro
Methanesulfonic acid, trichloroacetic acid.
Optionally, preparation in accordance with the present invention：
In the coupling reaction, the dosage of 9,9- dimethyl fluorene -2- boric acid is 1.05~1.2 equivalents；
In the addition reaction, butyl lithium dosage is 1.1~1.3 equivalents, and acetone dosage is 1.2~1.7 equivalents；
In the ring-closure reaction, the dosage of the acid is 4~10 equivalents.
It advanced optimizes, preparation in accordance with the present invention：
In the coupling reaction, the dosage of 9,9- dimethyl fluorene -2- boric acid is 1.1 equivalents；
In the addition reaction, butyl lithium dosage is 1.2 equivalents, and acetone dosage is 1.5 equivalents；
In the ring-closure reaction, the dosage of the acid is 6 equivalents.
Moreover, preparation in accordance with the present invention：
In the coupling reaction, after completion of the reaction, cooling, liquid separation, after organic layer washing, anhydrous sodium sulfate drying, silica gel
Column decolourizes, and eluent is concentrated to dryness, and tetrahydrofuran is added, obtains, containing the tetrahydrofuran solution of compound shown in formula M-1, containing
The tetrahydrofuran solution of compound shown in formula M-1 directly carries out addition reaction without further separating-purifying.
In the addition reaction, the tetrahydrofuran solution containing compound shown in formula M-1 is cooled to -78 DEG C, elder generation and butyl
Lithium reacts, and prepares corresponding lithium salts, then carries out addition reaction with acetone, then hydrolyzes, dichloromethane extraction, anhydrous sodium sulfate
It is dry, after filtering off drier, the dichloromethane solution containing compound shown in formula M-2 is obtained, compound shown in formula M-2 is contained
Dichloromethane solution directly carries out ring-closure reaction without further separating-purifying.
Optionally, preparation in accordance with the present invention, in the ring-closure reaction, the acid is Loprazolam or trifluoro methylsulphur
Acid.
Optionally, preparation in accordance with the present invention, in the ring-closure reaction, the acid is trichloroacetic acid, because of trichlorine
Acetic acid is that solid uses the dichloromethane solution of trichloroacetic acid in operation at room temperature.
Optionally, preparation in accordance with the present invention, ring-closure reaction are reacted in dichloromethane solvent, Loprazolam
It is added dropwise to reaction system at -10~0 DEG C, after Loprazolam is added dropwise, reaction system reacts 60min at 20~30 DEG C, obtains
6,6,12,12- tetramethyls -6,12- dihydros shown in formula M indeno [1,2-b] fluorenes.
The present invention has the beneficial effect that：
Preparation in accordance with the present invention, it is simple for process, reaction condition is mild, easy to operate；Required raw material is easy to get, cost
It is cheap；And yield is up to 77~90%；Therefore it is suitble to large-scale production.
Specific implementation mode
Specific embodiment is only the description of the invention, below will knot without constituting the limitation to the content of present invention
Closing specific embodiment, invention is further explained and description.
According to the preparation method of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes of the invention, this method packet
It includes：
Coupling reaction：With the o-dibromobenzene of 1 equivalent and 9, the 9- dimethyl fluorene -2- boric acid of 1~1.4 equivalent be coupled anti-
It answers, compound shown in production M-1；
Addition reaction：Compound shown in formula M-1 is first reacted with the butyl lithium of 1~1.5 equivalent, then with the third of 1~2 equivalent
Ketone carries out addition reaction, then hydrolyzes, compound shown in production M-2；
Ring-closure reaction：Compound shown in formula M-2 carries out ring-closure reaction in the presence of the acid of 3~16 equivalents, is converted into formula M institutes
6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes shown；
In the preparation method of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes of the invention, preparation method
Including three coupling reaction, addition reaction, ring-closure reaction steps.
In coupling reaction, carried out using the o-dibromobenzene of 1 equivalent and 9, the 9- dimethyl fluorene -2- boric acid of 1~1.4 equivalent
Coupling reaction, compound shown in production M-1, reaction equation are as follows：
At this in step reaction, 9,9- dimethyl fluorene -2- boric acid are excessive so that o-dibromobenzene reaction is abundant, avoids neighbour two
The residue of bromobenzene, although by-product shown in a small amount of formula M-3 can be generated, by-product is in subsequent addition reaction shown in formula M-3
With cannot participate in reaction in ring-closure reaction, can very easily be removed from product, therefore after the completion of coupling reaction, through locating later
Reason, obtaining the tetrahydrofuran solution containing compound shown in formula M-1 it is anti-can directly to carry out addition without further separating-purifying
It answers, and subsequent reaction is not adversely affected.
In addition reaction, compound shown in formula M-1 first and 1~1.5 equivalent butyl lithium react, then with 1~2 equivalent
Acetone carry out addition reaction, then hydrolyze, compound shown in production M-2, reaction equation is as follows：
At this in step reaction, the tetrahydrofuran solution containing compound shown in formula M-1 is cooled to -78 DEG C, elder generation and butyl lithium
Reaction, prepares corresponding lithium salts, then carries out addition reaction with acetone, then hydrolyzes, dichloromethane extraction, and anhydrous sodium sulfate is dry
It is dry, after filtering off drier, the dichloromethane solution containing compound shown in formula M-2 is obtained, two containing compound shown in formula M-2
Chloromethanes solution directly carries out ring-closure reaction without further separating-purifying.
In ring-closure reaction, compound shown in formula M-2 carries out ring-closure reaction in the presence of the acid of 3~16 equivalents, is converted into
6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes, reaction equation shown in formula M are as follows：
At this in step reaction, acid is Loprazolam, trifluoromethanesulfonic acid or trichloroacetic acid.
According to the preparation method of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes of the invention, Loprazolam
It is a kind of strong acid with trifluoromethanesulfonic acid, Loprazolam or trifluoromethanesulfonic acid is directly largely added in reaction, can be released a large amount of
Heat, so that reaction is aggravated, so Loprazolam or trifluoromethanesulfonic acid need to be added dropwise at low temperature when reaction system is added, can make
The amount of by-products that reaction generates minimizes, and increases the purity of product, improves product yield.Meanwhile be added dropwise Loprazolam or
Reaction temperature control finishes at -10~0 DEG C and is to slowly warm up to 20~30 DEG C, reaction is abundant, and reaction condition when trifluoromethanesulfonic acid
Mildly, easy to operate.
Because trichloroacetic acid is at room temperature solid, therefore in operation, when the acid chooses trichloroacetic acid, use
The dichloromethane solution of trichloroacetic acid is added dropwise in reaction by the dichloromethane solution of trichloroacetic acid.
It is provided according to the preparation method of 6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes of the present invention optional
Factor is more, and claim according to the present invention can be combined into different embodiments, and embodiment is only used for carrying out the present invention
It further describes, does not limit the invention.The present invention is further detailed below in conjunction with embodiment.
Embodiment 1
Synthetic route is as follows：
According to the preparation method of 6,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes of the invention, reaction point three
Step carries out：
(1) coupling reaction
23.59 grams of (0.1mol, 1eq) o-dibromobenzenes, 26.18 grams (0.11mol, 1.1eq) are added in 1000 milliliters of there-necked flasks
9,9- dimethyl fluorene -2- boric acid, 27.6 grams of (0.2mol, 2eq) potassium carbonate, 200 milliliters of toluene, 150 milliliters of ethyl alcohol, 80 milliliters
0.58 gram of (0.0005mol, 0.005eq) tetra-triphenylphosphine palladium is added under nitrogen protection for water, is slowly heated to 70~80 DEG C of reactions
8 hours, cooling added moisture liquid, and after organic layer washing, anhydrous sodium sulfate drying, silicagel column decolourizes, and eluent is concentrated to dryness, adds
Enter 300 milliliters of tetrahydrofurans, obtains the tetrahydrofuran solution containing compound shown in formula M-1.
(2) addition reaction
Under nitrogen protection, the tetrahydrofuran solution containing compound shown in formula M-1 that upper step obtains is cooled to -78 DEG C,
Temperature is controlled at -70~-78 DEG C, the hexane solution of the butyl lithium of 75 milliliters of (0.12mol, 1.2eq) 1.6M is slowly added dropwise, adds
Finish and kept for -70~-78 DEG C 40 minutes, then controls -70~-78 DEG C, be slowly added to 8.7 grams of (0.15mol, 1.5eq) acetone, add
Finish by reaction solution be to slowly warm up to 25 DEG C react 1 hour, be slowly added to ammonium chloride solution hydrolysis, then be added 100 milliliters of dichloros
Methane and 200 milliliters of moisture liquid, water layer are extracted with 50 milliliters of dichloromethane, and combined dichloromethane layer washes dichloromethane layer,
Saturated common salt is washed, and after anhydrous sodium sulfate drying, anhydrous sodium sulfate is removed by filtration, is obtained containing compound shown in formula M-2
Dichloromethane solution.
(3) ring-closure reaction
The dichloromethane solution containing compound shown in formula M-2 that upper step obtains is cooled to -10 DEG C, by 58g
(0.6mol, 6eq) Loprazolam is slowly added dropwise into dichloromethane solution, and reaction system is maintained at 0~-10 DEG C to Loprazolam
It being added dropwise, reaction system is to slowly warm up to 20~30 DEG C of reaction 60min, is filtered, washing, methanol is washed, and obtains 6,6,12,
12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes 27.82g, product yield 89.74%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 2
The dosage of 9,9- dimethyl fluorenes -2- boric acid in first step coupling reaction is only changed to by synthetic method with embodiment 1
0.12mol obtains 27.60g products, product yield 89.03%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 3
The dosage of 9,9- dimethyl fluorenes -2- boric acid in first step coupling reaction is only changed to by synthetic method with embodiment 1
0.13mol obtains 25.60g products, product yield 82.58%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 4
The dosage of 9,9- dimethyl fluorenes -2- boric acid in first step coupling reaction is only changed to by synthetic method with embodiment 1
0.14mol obtains 23.94g products, product yield 77.22%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 5
The dosage of butyl lithium in second step addition reaction is only changed to 0.13mol, obtained by synthetic method with embodiment 1
To 27.77g products, product yield 89.58%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 6
The dosage of butyl lithium in second step addition reaction is only changed to 0.14mol, obtained by synthetic method with embodiment 1
To 27.80g products, product yield 89.67%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 7
The dosage of acetone in second step addition reaction is only changed to 0.13mol, obtained by synthetic method with embodiment 1
27.83g products, product yield 89.77%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 8
The dosage of acetone in second step addition reaction is only changed to 0.17mol, obtained by synthetic method with embodiment 1
27.81g products, product yield 89.70%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 9
The dosage of acetone in second step addition reaction is only changed to 0.2mol, obtained by synthetic method with embodiment 1
27.70g products, product yield 89.35%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 10
The amount of Loprazolam is only changed to 0.4mol by synthetic method with embodiment 1 by 0.6mol, obtains 25.18g productions
Product, product yield 81.22%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 11
The amount of Loprazolam is only changed to 0.95mol by synthetic method with embodiment 1 by 0.6mol, obtains 26.71g productions
Product, product yield 86.16%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 12
The amount of Loprazolam is only changed to 1.2mol by synthetic method with embodiment 1 by 0.6mol, obtains 26.02g productions
Product, product yield 83.93%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 13
The amount of Loprazolam is only changed to 1.5mol by synthetic method with embodiment 1 by 0.6mol, obtains 23.88g productions
Product, product yield 77.03%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 14
The Loprazolam of 0.6mol is only changed to the trifluoromethanesulfonic acid of 0.6mol, obtained by synthetic method with embodiment 1
26.97g products, product yield 87.00%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
Embodiment 15
The Loprazolam of 0.6mol is only changed to 50 milliliters of the trichloroacetic acid of 0.6mol by synthetic method with embodiment 1
Dichloromethane solution obtains 25.91g products, product yield 83.58%.
Obtained product is carried out1HNMR is detected,1HNMR spectrum analysis data are as follows：1HNMR (500MHz, CDCl3)：
8.07 (m, 2H), 7.98 (s, 2H), 7.55 (m, 2H), 7.44 (m, 2H), 7.28 (m, 2H), 1.70 (2,12H).
Obtained product Mass Spectrometer Method is subjected to, obtained m/e values are 310.
It is simple for process, reaction condition is mild, easy to operate it can be seen that preparation in accordance with the present invention；Required raw material
It is easy to get, is of low cost, yield is suitble to large-scale production between 77~90%.
Obviously, various changes and modifications can be made to the invention without departing from essence of the invention by those skilled in the art
God and range.In this way, if these modifications and changes of the present invention belongs to the range of the claims in the present invention and its equivalent technologies
Within, then the present invention is also intended to include these modifications and variations.
Claims (5)
1. a kind of preparation method of 6,6,12,12- tetramethyls -6,12- dihydros indeno [1,2-b] fluorenes：
(1) coupling reaction
23.59 grams of o-dibromobenzenes, 26.18 grams of 9,9- dimethyl fluorene -2- boric acid, 27.6 grams of carbonic acid are added in 1000 milliliters of there-necked flasks
0.58 gram of tetra-triphenylphosphine palladium, slow heating are added under nitrogen protection for potassium, 200 milliliters of toluene, 150 milliliters of ethyl alcohol, 80 milliliters of water
It is reacted 8 hours to 70~80 DEG C, cooling, adds moisture liquid, after organic layer washing, anhydrous sodium sulfate drying, silicagel column decoloration, elution
Liquid is concentrated to dryness, and 300 milliliters of tetrahydrofurans are added, obtain the tetrahydrofuran solution containing compound shown in formula M-1；
(2) addition reaction
Under nitrogen protection, the tetrahydrofuran solution containing compound shown in formula M-1 that upper step obtains is cooled to -78 DEG C, control
The hexane solution of the butyl lithium of 75 milliliters of 1.6M is slowly added dropwise at -70~-78 DEG C in temperature, finishes -70~-78 DEG C 40 of holding
Minute, -70~-78 DEG C are then controlled, 8.7 grams of acetone are slowly added to, finishes that reaction solution is to slowly warm up to 25 DEG C of reactions is 1 small
When, it is slowly added to ammonium chloride solution hydrolysis, 100 milliliters of dichloromethane and 200 milliliters of moisture liquid are then added, water layer is with 50 milliliters
Dichloromethane extracts, and combined dichloromethane layer washes dichloromethane layer, saturated common salt washing, will after anhydrous sodium sulfate drying
Anhydrous sodium sulfate is removed by filtration, and obtains the dichloromethane solution containing compound shown in formula M-2；
(3) ring-closure reaction
The dichloromethane solution containing compound shown in formula M-2 that upper step obtains is cooled to -10 DEG C, 58g Loprazolams are delayed
Slowly it is added dropwise in dichloromethane solution, reaction system is maintained at 0~-10 DEG C and is added dropwise to Loprazolam, and reaction system is delayed
It is slow to be warming up to 20~30 DEG C of reaction 60min, it filters, washing, methanol is washed, and 6,6,12,12- tetramethyl -6,12- dihydro indenos are obtained
[1,2-b] fluorenes.
2. the preparation method of according to claim 16,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes,
In in the reaction of (3) step, the amount of Loprazolam is 0.4mol.
3. the preparation method of according to claim 16,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes,
In in the reaction of (3) step, the amount of Loprazolam is 0.95mol.
4. the preparation method of according to claim 16,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes,
In (3) step reaction in, the Loprazolam of 0.6mol is changed to the trifluoromethanesulfonic acid of 0.6mol.
5. the preparation method of according to claim 16,6,12,12- tetramethyl -6,12- dihydro indeno [1,2-b] fluorenes,
In (3) step reaction in, the Loprazolam of 0.6mol is changed to 50 milliliters of dichloromethane solutions of the trichloroacetic acid of 0.6mol.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460434A (en) * | 2006-06-02 | 2009-06-17 | 默克专利有限公司 | Materials for organic electroluminescent devices |
| CN101490207A (en) * | 2006-07-11 | 2009-07-22 | 默克专利有限公司 | Novel materials for organic electroluminescent devices |
| CN103570628A (en) * | 2012-07-27 | 2014-02-12 | 昆山维信诺显示技术有限公司 | Benzoindenofluorene derivative containing pyrimidyl or pyrazinyl or triazinyl group, and its application |
| KR20140134884A (en) * | 2013-05-15 | 2014-11-25 | 에스에프씨 주식회사 | An electroluminescent compound and an electroluminescent device comprising the same |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101460434A (en) * | 2006-06-02 | 2009-06-17 | 默克专利有限公司 | Materials for organic electroluminescent devices |
| CN101490207A (en) * | 2006-07-11 | 2009-07-22 | 默克专利有限公司 | Novel materials for organic electroluminescent devices |
| CN103570628A (en) * | 2012-07-27 | 2014-02-12 | 昆山维信诺显示技术有限公司 | Benzoindenofluorene derivative containing pyrimidyl or pyrazinyl or triazinyl group, and its application |
| KR20140134884A (en) * | 2013-05-15 | 2014-11-25 | 에스에프씨 주식회사 | An electroluminescent compound and an electroluminescent device comprising the same |
Non-Patent Citations (1)
| Title |
|---|
| Sterically congested quinone methides in photodehydration reactions of 4-hydroxybiphenyl derivatives and investigation of their antiproliferative activity;Nikola Basaric等;《Photochem. Photobiol. Sci.》;20111231;第10卷;第1910-1925页 * |
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