CN109456350A - Dibenzofurans/thiophene -4- boric acid synthetic method - Google Patents
Dibenzofurans/thiophene -4- boric acid synthetic method Download PDFInfo
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- dibenzofurans
- thiophene
- boric acid
- synthetic method
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- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 title claims abstract description 48
- 150000004826 dibenzofurans Chemical class 0.000 title claims abstract description 41
- 239000004327 boric acid Substances 0.000 title claims abstract description 33
- 229930192474 thiophene Natural products 0.000 title claims abstract description 24
- 238000010189 synthetic method Methods 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical class C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 claims abstract description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims abstract description 15
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 14
- 239000012043 crude product Substances 0.000 claims abstract description 13
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical class 0.000 claims abstract description 9
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 8
- 229910000085 borane Inorganic materials 0.000 claims abstract description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 11
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- 238000005352 clarification Methods 0.000 claims description 6
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
- 229910052796 boron Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 3
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical group C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 claims description 3
- CETVQRFGPOGIQJ-UHFFFAOYSA-N lithium;hexane Chemical compound [Li+].CCCCC[CH2-] CETVQRFGPOGIQJ-UHFFFAOYSA-N 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000002240 furans Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- -1 heterocyclic boronic acids Chemical class 0.000 abstract description 4
- 230000003321 amplification Effects 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000002994 raw material Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 5
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000005829 trimerization reaction Methods 0.000 description 2
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- JEYWNNAZDLFBFF-UHFFFAOYSA-N Nafoxidine Chemical compound C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 JEYWNNAZDLFBFF-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005360 mashing Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229950002366 nafoxidine Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses dibenzofurans/thiophene -4- boric acid synthetic method, belongs to heterocyclic boronic acids in organic chemistry and synthesize field.Using dibenzofurans or dibenzothiophenes, it is added lithium alkylide and TMEDA, after back flow reaction, is cooled to General low temperature, halogen borane reagent is added dropwise, is added after acid is quenched, obtained crude product purifies to obtain dibenzofurans/thiophene -4- boric acid using alcohol/aqueous systems.This method is easy to operate, avoids ultralow temperature in traditional handicraft and reacts, industrial amplification production is suitble to use.
Description
Technical field
The present invention relates to the synthetic method of dibenzo-heterocyclic boric acid more particularly to the conjunctions of dibenzofurans/thiophene -4- boric acid
At method, belongs to heterocyclic boronic acids in organic chemistry and synthesize field.
Background technique
Dibenzofurans/thiophene -4- boric acid: including dibenzofurans -4- boric acid and dibenzothiophenes -4- boric acid, pass through
It is applied in OLED material after Suzuki coupling, it is swift and violent to increase development for application in recent years.Both product chemical property are similar,
Synthetic method is also similar, therefore is substantially the same in document or publication using synthetic method.
Existing synthetic method is divided into two classes: one kind is using dibenzofurans or dibenzothiophenes by 4- bromo-derivatives
Intermediate stage synthesizes dibenzofurans/thiophene -4- boric acid.Using under dibenzofurans or dibenzothiophenes ultralow temperature, and just
Butyl lithium or s-butyl lithium deprotonation, with bromide reagent generate 4 bromo-derivatives, then under ultralow temperature then with trimethylborate
Or triisopropyl borate ester reacts, and obtains product after re crystallization from toluene.
In addition a kind of for using dibenzofurans or dibenzothiophenes one-step synthesis dibenzofurans/thiophene -4- boric acid.Using two
Under benzofuran or dibenzothiophenes ultralow temperature, deprotonation is carried out with n-BuLi or s-butyl lithium, directly under maintenance ultralow temperature,
It is reacted with trimethylborate or triisopropyl borate ester, product is obtained after re crystallization from toluene.
Above two method is required to have certain limitation to equipment using being reacted under ultralow temperature, and difficult point is control
Monosubstituted and disubstituted ratio, different documents or patent yield report difference are very big, in comparison, using by bromo
The method reproducibility of object intermediate is more preferable.In addition, product can be dehydrated generation trimerization during being heated up using re crystallization from toluene
Body, product after purification are the mixture of monomer and tripolymer, are not easy to be found when detecting.
Summary of the invention
In order to overcome drawbacks described above, the present invention provides dibenzofurans/thiophene -4- boric acid synthetic methods.Using two
Benzofuran or dibenzothiophenes, are added lithium alkylide and TMEDA, after back flow reaction, are cooled to General low temperature, the examination of halogen boron is added dropwise
Agent, after addition acid is quenched, obtained crude product purifies to obtain dibenzofurans/thiophene -4- boric acid using alcohol/aqueous systems.This method
It is easy to operate, it avoids ultralow temperature in traditional handicraft and reacts, industrial amplification production is suitble to use.
Dibenzofurans/thiophene -4- boric acid synthetic method, includes the following steps: dibenzofurans or dibenzo thiophene
Pheno, is added lithium alkylide and TMEDA, after back flow reaction, is cooled to General low temperature, halogen borane reagent is added dropwise, and is added after acid is quenched, obtains
Crude product purify to obtain dibenzofurans/thiophene -4- boric acid using alcohol/aqueous systems.Above-mentioned reaction equation are as follows:
Further, in the above-mentioned technical solutions, lithium alkylide uses n-BuLi or hexyllithium, n-BuLi using 1.6M or
2.5M hexane solution, hexyllithium use 2.3M or 2.47M hexane solution.Lithium alkylide be added equivalent be raw material dibenzofurans or
The 1-1.3 equivalent of dibenzothiophenes, optimum response equivalent are 1.1-1.2 equivalent, will appear apparent two when more than 1.5 equivalent and take
For product.
Further, in the above-mentioned technical solutions, alkane solvent is added in dibenzofurans or dibenzothiophenes, followed by adding
After entering TMEDA, lower dissolved clarification is stirred, lithium alkylide is finally added dropwise.Alkane solvent includes pentane, hexane, heptane etc..
Further, in the above-mentioned technical solutions, lithium alkylide and TMEDA equivalent proportion are 1:1-1.1.It is preferred that equivalent proportion is
1: 1。
Further, in the above-mentioned technical solutions, General low temperature is -20 DEG C to 0 DEG C of temperature.
Further, in the above-mentioned technical solutions, halogen borane reagent is selected from ClB (NMe2) 2, ClB (NEt2) 2, ClB (Ni-
Pr2) 2, ClB (NPyrroli) 2, BrB (NMe2) 2, BrB (NEt2) 2, BrB (Ni-Pr2) 2 or BrB (NPyrroli) 2 etc..Its
In, Pyrroli represents nafoxidine.
Above-mentioned halogen borane reagent additional amount is the 1-1.4 equivalent of raw material dibenzofurans or dibenzothiophenes, the amount of being preferably added to
It is 1.05-1.1 times of lithium alkylide equivalent.
Further, in the above-mentioned technical solutions, acid used in being quenched be hydrochloric acid, sulfuric acid or hydrobromic acid, acetic acid etc., it is excellent
Select 5-15% aqueous hydrochloric acid solution.
Further, in the above-mentioned technical solutions, alcohol/aqueous systems purification process is, after crude product addition alcohol is completely dissolved,
It is precipitated after adding water stirring, in precipitation process, in order to accelerate speed of separating out, catalytic amount acid can be added dropwise to.The alcohol is first
Alcohol, ethyl alcohol, isopropanol, n-butanol, preferably methanol.
The good effect that the present invention generates
The present invention uses dibenzofurans or dibenzothiophenes, is added lithium alkylide and TMEDA, after back flow reaction, is cooled to common
Halogen borane reagent is added dropwise in low temperature, and after addition acid is quenched, obtained crude product purifies to obtain dibenzofurans/thiophene using alcohol/aqueous systems
Pheno -4- boric acid.This method is easy to operate, avoids ultralow temperature in traditional handicraft and reacts, industrial amplification production is suitble to use.Afterwards
Processing purifying avoids in such a way that alcohol dissolution elutriation goes out and generates trimerization during using re crystallization from toluene in traditional handicraft
Body.
Specific embodiment
Embodiment 1
Under nitrogen protection, dibenzofurans (16.8g, 0.1mol) and n-hexane 85mL are added in reaction flask, is then added
TMEDA (12.8g, 0.11mol), becomes clear solution under stirring, be then added dropwise to 1.6M n-BuLi hexane solution (68mL,
0.11mol), then raise temperature to back flow reaction 2 hours, be then cooled to -10 DEG C, start be added dropwise ClB (NMe2) 2 (15.5g,
95% purity contains 3-5%B (NMe2) 3,0.11mol), it is added dropwise, insulated and stirred is reacted 4-5 hours, and TLC detection raw material disappears
It loses, is added dropwise to 10% aqueous hydrochloric acid solution and is quenched, adjust pH=2-3, control temperature is no more than 10 DEG C during being quenched, 150mL
Ethyl acetate is extracted twice, after organic layer is evaporated, after methanol (about 20-22mL) stirring to the complete dissolved clarification of crude product is added, then slowly
It is added dropwise to 4 times of quantity of methyl alcohol water (about 80-85mL) and is all precipitated to solid, filtering obtains off-white powder dibenzo furan after drying
Mutter -4- boric acid 16.3g, and yield 77%, HPLC:98.9%, HNMR structure meets, consistent with document.
Embodiment 2
Under nitrogen protection, dibenzofurans (16.8g, 0.1mol) and n-hexane 85mL are added in reaction flask, is then added
TMEDA (12.8g, 0.11mol), becomes clear solution under stirring, be then added dropwise to 1.6M n-BuLi hexane solution (68mL,
0.11mol), then raise temperature to back flow reaction 2 hours, be then cooled to 0 DEG C, start be added dropwise ClB (Ni-Pr2) 2 (25.8g,
99% purity, 0.105mol), it is added dropwise, insulated and stirred is reacted 6-8 hours, and TLC detects raw material and disappears, and is added dropwise to 10% hydrochloric acid
Aqueous solution is quenched, and pH=2-3 is adjusted, and control temperature is no more than 10 DEG C during being quenched, and 150mL ethyl acetate is extracted twice,
After organic layer is evaporated, after methanol (22mL) stirring to the complete dissolved clarification of crude product is added, then it is slowly added dropwise into 4 times of quantity of methyl alcohol water (88mL)
It is all precipitated to solid, filtering obtains off-white powder dibenzofurans -4- boric acid 18.7g after drying, yield 88%, HPLC:
99.2%, HNMR structure meet, consistent with document.
This reaction can also detect after reaction, and directly distillation is warming up under 130-160 DEG C of high vacuum using oil bath,
By way of rectifying after purification by intermediate rectifying, 10% hydrochloric acid tune pH=2-3, ethyl acetate extraction, organic layer rotation are added
After steaming, white products, yield 84% are obtained after heptane mashing is added.
Embodiment 3
Under nitrogen protection, dibenzofurans (16.8g, 0.1mol) and n-hexane 85mL are added in reaction flask, is then added
TMEDA (13.9g, 0.12mol), becomes clear solution under stirring, be then added dropwise to 2.5M n-BuLi hexane solution (45mL,
0.11mol), then raise temperature to back flow reaction 2 hours, be then cooled to -10 DEG C, start be added dropwise BrB (NMe2) 2 (19.5g,
99% purity, 0.11mol), it is added dropwise, insulated and stirred is reacted 3 hours, and TLC detects raw material and disappears, the solid of generation is filtered out,
It is cooled to -10 DEG C again, is added dropwise to 10% aqueous hydrochloric acid solution and is quenched, adjusts pH=2-3, control temperature does not surpass during being quenched
10 DEG C are crossed, 150mL ethyl acetate is extracted twice, and after organic layer is evaporated, it is completely molten to crude product that methanol (about 20-22mL) stirring is added
It after clear, then be slowly added dropwise and be all precipitated into 4 times of quantity of methyl alcohol water (about 80-85mL) to solid, it is solid to obtain off-white color for filtering after drying
Body dibenzofurans -4- boric acid 17.4g, yield 82%, HPLC:99.6%, HNMR structure meets, consistent with document.
Embodiment 4
Under nitrogen protection, dibenzothiophenes (18.4g, 0.1mol) and hexamethylene 105mL are added in reaction flask, is then added
TMEDA (12.8g, 0.11mol), becomes clear solution under stirring, be then added dropwise to 1.6M n-BuLi hexane solution (68mL,
0.11mol), then raise temperature to back flow reaction 2 hours, be then cooled to -10 DEG C, start be added dropwise ClB (NMe2) 2 (15.5g,
95% purity contains 3-5%B (NMe2) 3,0.11mol), it is added dropwise, insulated and stirred reaction, TLC detects raw material and disappears, and is added dropwise
Enter 10% aqueous hydrochloric acid solution to be quenched, adjust pH=2-3, control temperature is no more than 10 DEG C during being quenched, 180mL ethyl acetate
It is extracted twice, after organic layer is evaporated, after methanol (about 21-24mL) stirring to the complete dissolved clarification of crude product is added, then is slowly added dropwise into 4 times
Quantity of methyl alcohol water (about 82-90mL) is all precipitated to solid, and filtering obtains white solid dibenzothiophenes -4- boric acid after drying
18.5g, yield 81%, HPLC:99.5%, HNMR structure meets, consistent with document.
Embodiment 5
Under nitrogen protection, dibenzothiophenes (18.4g, 0.1mol) and n-hexane 85mL are added in reaction flask, is then added
TMEDA (12.8g, 0.11mol), becomes clear solution under stirring, be then added dropwise to 2.3M n-HexylLi hexane solution
(48mL, 0.11mol), then raises temperature to back flow reaction 2 hours, is then cooled to 0 DEG C, starts that BrB (NMe2) 2 is added dropwise
(18.7g, 99% purity, 0.105mol), is added dropwise, and insulated and stirred reaction, TLC detects raw material and disappears, and filters out generation
Solid is cooled to 0 DEG C again, is added dropwise to 10% aqueous hydrochloric acid solution and is quenched, and adjusts pH=2-3, controls temperature during being quenched
No more than 10 DEG C, 180mL ethyl acetate is extracted twice, and after organic layer is evaporated, it is completely molten to crude product that methanol (25mL) stirring is added
It after clear, then be slowly added dropwise and be all precipitated into about 4 times of quantity of methyl alcohol water (105mL) to solid, filtering obtains white solid two after drying
Benzothiophene -4- boric acid 20.7g, yield 91%, HPLC:99.1%, HNMR structure meets, consistent with document.
Embodiment 6
Under nitrogen protection, dibenzothiophenes (18.4g, 0.1mol) and n-hexane 85mL are added in reaction flask, is then added
TMEDA (12.8g, 0.11mol), becomes clear solution under stirring, be then added dropwise to 1.6M n-BuLi hexane solution (68mL,
0.11mol), then raise temperature to back flow reaction 2 hours, be then cooled to 0 DEG C, start be added dropwise ClB (Ni-Pr2) 2 (25.8g,
99% purity, 0.105mol), be added dropwise, insulated and stirred reaction, TLC detect raw material disappear, be added dropwise to 10% aqueous hydrochloric acid solution into
Row is quenched, and adjusts pH=2-3, and control temperature is no more than 10 DEG C during being quenched, and 180mL ethyl acetate is extracted twice, and organic layer steams
After dry, after ethyl alcohol (30- 35mL) stirring to the complete dissolved clarification of crude product is added, then it is slowly added dropwise into about 3 times of amount of alcohol water (90-
105mL) all it is precipitated to solid, filtering obtains white solid dibenzothiophenes -4- boric acid 20.3g after drying, yield 89%,
HPLC:99.4%, HNMR structure meet, consistent with document.
Embodiment above describes basic principles and main features of the invention and advantages.The technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (10)
1. dibenzofurans/thiophene -4- boric acid synthetic method, which comprises the steps of: by dibenzofurans or
Dibenzothiophenes is mixed with alkane solvent, addition lithium alkylide and TMEDA, after back flow reaction, is cooled to General low temperature, halogen boron is added dropwise
Reagent, after addition acid is quenched, obtained crude product purifies to obtain dibenzofurans/thiophene -4- boric acid using alcohol/aqueous systems.
2. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: lithium alkylide is selected from
1-1.3 times that equivalent is dibenzofurans or dibenzothiophenes is added in n-BuLi or hexyllithium.
3. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: alkane solvent packet
Include pentane, hexane or heptane.
4. according to claim 1 or 3 dibenzofurans/thiophene -4- boric acid synthetic method, it is characterised in that: dibenzo
Alkane solvent is added in furans or dibenzothiophenes, after TMEDA is added, stirs lower dissolved clarification, lithium alkylide is finally added dropwise.
5. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: lithium alkylide with
TMEDA equivalent proportion is 1:1-1.1.
6. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: General low temperature is
- 20 DEG C to 0 DEG C of temperature.
7. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that the choosing of halogen borane reagent
From ClB (NMe2) 2, ClB (NEt2) 2, ClB (Ni-Pr2) 2, ClB (NPyrroli) 2, BrB (NMe2) 2, BrB (NEt2) 2, BrB
(Ni-Pr2) 2 or BrB (NPyrroli) 2.
8. according to claim 1 or 7 dibenzofurans/thiophene -4- boric acid synthetic method, it is characterised in that: the examination of halogen boron
Agent additional amount is the 1-1.4 equivalent of dibenzofurans or dibenzothiophenes, is the 1.05-1.1 equivalent of lithium alkylide.
9. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: used in being quenched
Acid be hydrochloric acid, sulfuric acid, hydrobromic acid or acetic acid.
10. dibenzofurans/thiophene -4- boric acid synthetic method according to claim 1, it is characterised in that: alcohol/aqueous systems
Purification process is after being completely dissolved crude product addition alcohol, to be precipitated after adding water stirring.
Priority Applications (1)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20110017983A1 (en) * | 2008-03-05 | 2011-01-27 | Idemitsu Kosan Co., Ltd. | Polymer and organic electroluminescent device including the same |
| CN102718785A (en) * | 2012-06-18 | 2012-10-10 | 浙江凯普化工有限公司 | Method for preparing aromatic ring boric acid |
| CN104876956A (en) * | 2015-06-12 | 2015-09-02 | 沧州普瑞东方科技有限公司 | One-pot synthesis process for boron-amine compounds |
| US20170125678A1 (en) * | 2015-10-30 | 2017-05-04 | Nanjing Topto Materials Co., Ltd. | Novel organic compound, material comprising the same for organic electroluminescence devices, and organic electroluminescence device comprising the material |
| CN107892699A (en) * | 2017-12-17 | 2018-04-10 | 沧州普瑞东方科技有限公司 | A kind of synthesis technique of the boric acid of pyridine 4 |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20110017983A1 (en) * | 2008-03-05 | 2011-01-27 | Idemitsu Kosan Co., Ltd. | Polymer and organic electroluminescent device including the same |
| CN102718785A (en) * | 2012-06-18 | 2012-10-10 | 浙江凯普化工有限公司 | Method for preparing aromatic ring boric acid |
| CN104876956A (en) * | 2015-06-12 | 2015-09-02 | 沧州普瑞东方科技有限公司 | One-pot synthesis process for boron-amine compounds |
| US20170125678A1 (en) * | 2015-10-30 | 2017-05-04 | Nanjing Topto Materials Co., Ltd. | Novel organic compound, material comprising the same for organic electroluminescence devices, and organic electroluminescence device comprising the material |
| CN107892699A (en) * | 2017-12-17 | 2018-04-10 | 沧州普瑞东方科技有限公司 | A kind of synthesis technique of the boric acid of pyridine 4 |
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