CN104945426B - 一种合成芳基三氟硼酸钾的方法 - Google Patents
一种合成芳基三氟硼酸钾的方法 Download PDFInfo
- Publication number
- CN104945426B CN104945426B CN201510321581.3A CN201510321581A CN104945426B CN 104945426 B CN104945426 B CN 104945426B CN 201510321581 A CN201510321581 A CN 201510321581A CN 104945426 B CN104945426 B CN 104945426B
- Authority
- CN
- China
- Prior art keywords
- potassium
- substituted
- aryl
- boron
- reaction
- 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.)
- Active
Links
- 239000011591 potassium Substances 0.000 title claims abstract description 42
- 229910052700 potassium Inorganic materials 0.000 title claims abstract description 42
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 24
- 125000003118 aryl group Chemical group 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 10
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000007787 solid Substances 0.000 claims abstract description 19
- 150000001502 aryl halides Chemical class 0.000 claims abstract description 6
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
- -1 potassium aryl trifluoroborate salt Chemical class 0.000 claims abstract description 4
- VBKNTGMWIPUCRF-UHFFFAOYSA-M potassium;fluoride;hydrofluoride Chemical compound F.[F-].[K+] VBKNTGMWIPUCRF-UHFFFAOYSA-M 0.000 claims abstract description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 239000004327 boric acid Substances 0.000 claims description 30
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 17
- 229910052796 boron Inorganic materials 0.000 claims description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 14
- 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 claims description 13
- 229950002366 nafoxidine Drugs 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 10
- 238000010009 beating Methods 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 8
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 230000006837 decompression Effects 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 238000005292 vacuum distillation Methods 0.000 claims description 5
- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical compound NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 claims description 4
- WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 239000011698 potassium fluoride Substances 0.000 claims description 4
- 235000003270 potassium fluoride Nutrition 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- RBYGDVHOECIAFC-UHFFFAOYSA-L acetonitrile;palladium(2+);dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CC#N.CC#N RBYGDVHOECIAFC-UHFFFAOYSA-L 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical class C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 150000001716 carbazoles Chemical class 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 150000002240 furans Chemical class 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 150000002473 indoazoles Chemical class 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 150000003577 thiophenes Chemical class 0.000 claims description 2
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 235000011181 potassium carbonates Nutrition 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 4
- 239000011521 glass Substances 0.000 abstract description 3
- 238000005260 corrosion Methods 0.000 abstract description 2
- 230000007797 corrosion Effects 0.000 abstract description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 abstract 1
- CZKUZVHNYXOTAG-UHFFFAOYSA-N [B].[B].B(F)(F)F.[K] Chemical compound [B].[B].B(F)(F)F.[K] CZKUZVHNYXOTAG-UHFFFAOYSA-N 0.000 abstract 1
- XDZVHIGEPOJGNM-UHFFFAOYSA-N [B].[B].N1CCCC1.N1CCCC1.N1CCCC1.N1CCCC1 Chemical compound [B].[B].N1CCCC1.N1CCCC1.N1CCCC1.N1CCCC1 XDZVHIGEPOJGNM-UHFFFAOYSA-N 0.000 abstract 1
- 238000005271 boronizing Methods 0.000 abstract 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 229960004756 ethanol Drugs 0.000 description 5
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
- 238000006392 deoxygenation reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 1
- ZZPNDIHOQDQVNU-UHFFFAOYSA-N 2-hydroxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(O)OC1(C)C ZZPNDIHOQDQVNU-UHFFFAOYSA-N 0.000 description 1
- QUBJDMPBDURTJT-UHFFFAOYSA-N 3-chlorothiophene Chemical compound ClC=1C=CSC=1 QUBJDMPBDURTJT-UHFFFAOYSA-N 0.000 description 1
- NDZXVMFFUZCSMU-UHFFFAOYSA-N C(C1=CC=CC=C1)=O.[I] Chemical compound C(C1=CC=CC=C1)=O.[I] NDZXVMFFUZCSMU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical class [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 1
- 241001139947 Mida Species 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- OOPSAZSKOMIGFX-UHFFFAOYSA-N boric acid;toluene Chemical compound OB(O)O.CC1=CC=CC=C1 OOPSAZSKOMIGFX-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- WDWDWGRYHDPSDS-UHFFFAOYSA-N methanimine Chemical compound N=C WDWDWGRYHDPSDS-UHFFFAOYSA-N 0.000 description 1
- MLSKXPOBNQFGHW-UHFFFAOYSA-N methoxy(dioxido)borane Chemical compound COB([O-])[O-] MLSKXPOBNQFGHW-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 150000002835 noble gases Chemical class 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N o-dihydroxy-benzene Natural products OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 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
- C07F5/027—Organoboranes and organoborohydrides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种合成芳基三氟硼酸钾的新方法。将四(四氢吡咯)联硼在过量醇或水中回流反应后得到四(烷氧基)联硼,加入氟氢化钾水溶液得到联硼酸三氟硼酸钾,该硼化试剂为白色晶状固体,对空气和湿气稳定,适合长时间存放。采用该试剂与芳基卤代物进行Suzuki偶联可以一步得到芳基三氟硼酸钾盐,操作简便,收率高,对玻璃设备和反应釜无腐蚀。
Description
技术领域
本发明涉及一种合成芳基三氟硼酸钾的新方法,属于硼化学合成技术领域。
背景技术
金属钯催化的交叉偶联,又称之为Suzuki偶联自1979年被首次报道以来,目前已经广泛应用于制药、电子工业和先进材料等领域,也成为构建复杂分子必不可少的有效手段。
作为偶联反应的重要原料,硼酸和硼酸酯的合成也一直是化学界关注的焦点,做为格氏或有机锂试剂与硼酸三甲酯合成硼酸方法的补充,对于某些复杂分子硼酸类化合物又相继发展出来了:联硼酸频那醇酯、联硼酸新戊二醇酯、联硼酸邻苯二酚酯和联硼酸作为偶联助剂用来合成相应的硼酸和硼酸酯。同时由于某些硼酸自身存在不稳定性,最近几年科学家开发出来硼酸的氢氧化锂盐,三氟硼酸钾盐(简称BF3K),甲基亚胺基二乙酸(简称MIDA)酯,1,8-二胺基萘(简称DMAN)酯保护等来解决了不稳定硼酸的制备和应用。其中,目前应用最为成熟的为三氟硼酸钾盐。
三氟硼酸钾盐的制备目前主要为从卤待物按照以上方法得到的硼酸或硼酸酯,接着与氟氢化钾直接反应后得到,或是通过硼酸或硼酸酯与氟化钾/酒石酸反应后得到。做有最直接有效的一步偶联方法合成,仍没有见到公开资料报道。
发明内容
为了克服已有合成方法的不足,本发明提供一种合成关键中间体联硼酸三氟硼酸钾的方法,该合成方法工艺重现性好,操作简便,产率高。采用该新型硼化试剂在与芳基卤在金属钯存在下发生Suzuki偶联后得到一系列芳基三氟硼酸钾。
本发明为实现上述目的所采用的技术方案是:一种合成芳基三氟硼酸钾的新方法,其特征在于包括以下步骤:
第一步:氮气保护下,将四(四氢吡咯)联硼在4-50当量醇或水中回流反应,将生成的四氢吡咯蒸馏出来,随后减压蒸馏得到四(烷氧基)联硼,接着加入甲醇和4-6当量氟氢化钾水溶液,室温搅拌反应1-3小时,反应液静置,分出下层,旋干后,加入丙酮打浆,过滤,晾干后得到联硼酸三氟硼酸钾,产品为白色晶状固体,本步收率为62-85%。
第二步:氮气保护下,将联硼酸三氟硼酸钾、芳基卤、催化剂、溶剂与无机碱水溶液混合,20~110℃反应过夜,检测反应结束后,硅藻土过滤,减压旋干反应液,加入丙酮后,过滤掉不溶性固体,滤液再次旋干,加入乙醚或甲基叔丁基醚打浆后得到芳基三氟硼酸钾,本步收率42-80%。
进一步地,在上述技术方案中,所述第一步醇选自:甲醇、乙醇、异丙醇。
进一步地,在上述技术方案中,所述第一步选自醇时,减压蒸馏后,得到无色液体四烷氧基联硼;选自水时,蒸馏出四氢吡咯后,反应液降温,直接过滤得到白色固体四羟基联硼。
进一步地,在上述技术方案中,所述第二步中,芳基选自苯基或取代苯基、呋喃基或取代呋喃基、噻吩基或取代噻吩基、吡啶或取代吡啶基、吡唑基或取代吡唑基和恶唑或取代恶唑基、吲哚基或取代吲哚基、咔唑或取代咔唑、吲唑或取代吲唑;卤选自氯、溴或碘。
进一步地,在上述技术方案中,所述第二步中,催化剂需提前制备,选自Pd(OAc)2、Pd2(dba)3、PdCl2(CH3CN)2、PdCl2(PhCN)2与Cy3P、t -Bu3P、X-Phos、S-Phos和苯乙胺、联苯-2-胺三者任意组合反应。
进一步地,在上述技术方案中,所述第二步中,所述无机碱选自氟化钾、磷酸钾、碳酸钾或醋酸钾。
进一步地,在上述技术方案中,所述第二步中,溶剂选自甲醇、乙醇、异丙醇、四氢呋喃、二氧六环、二甲基亚砜或二甲基甲酰胺。
进一步地,在上述技术方案中,所述第二步中,联硼酸三氟硼酸钾、芳基卤、钯催化剂、无机碱的摩尔比为1-2:1:0.01-0.03:1.5-3。
所述整个反应都需要在惰性气体如氩气、氮气等保护下进行反应。
发明有益效果:
该方法所得到的新型硼化试剂联硼酸三氟硼酸钾,稳定性好,对空气和湿气不敏感,敞口放置三个月性质无任何变化。采用该试剂一步就可以偶联后得到芳基三氟硼酸钾,避免了以往合成方法中需要经过两步才能获得的缺点,提供了一条更简便、直接高效合成该类化合物的途径。
以往采用先成硼酸再加氟氢化钾的制备芳基三氟硼酸钾的方法中,不可避免地会产生氟化氢对玻璃产生严重的腐蚀。采用联硼酸三氟硼酸钾偶联反应得到芳基三氟硼酸钾的方法,即使重复多次使用,玻璃仪器依然完好。
具体实施方式:
实施例1:
联硼酸三氟硼酸钾的合成:
氮气保护下,在配备有滴加和回流装置的三口瓶内,加入四(四氢吡咯)联硼(0.15摩尔)和18-20当量无水乙醇,升温至回流反应。回流约1-2小时后,开始更换为常压蒸馏装置,将反应过程中生成四氢吡咯蒸馏出来,此时乙醇溶剂也会同时被带出,整个蒸馏过程中需要从滴加漏斗中补充乙醇。待蒸馏出来的溶剂中不再含有四氢吡咯时,取反应液气相检测确认反应完全,此时降温后,减压精馏后得到25.9克无色液体,HNMR和GC-MS确认为四(乙氧基)联硼。加入120毫升甲醇,搅拌均匀后,再加入KHF2水溶液(0.54摩尔),室温下搅拌1小时,体系静置后分层,小心分出下层后,减压蒸馏至干。加入丙酮打浆后过滤,得到21.5克白色晶状固体联硼酸三氟硼酸钾,总收率67%,11BNMR(DMSO-d6,128MHz):0.60ppm。
实施例2:
联硼酸三氟硼酸钾的合成:
氮气保护下,在配备有滴加和回流装置的三口瓶内,加入四(四氢吡咯)联硼(0.1摩尔)和50-60倍去离子水,升温至100℃回流反应。回流1.5小时后,更换为常压蒸馏装置,将反应过程中生成四氢吡咯蒸馏出来,待不再用四氢吡咯蒸出时,将反应液冷却至室温,此时有固体析出,过滤干燥后得到8.5克白色固体四羟基联硼,HNMR纯度98%以上,与文献一致。加入45毫升甲醇,室温搅拌至完全溶解后(大约需要10-15分钟),再加入KHF2水溶液(0.38摩尔),室温下搅拌1小时,体系静置后分层,小心分出下层后,减压蒸馏至干。加入丙酮打浆后过滤,得到15.8克白色固体联硼酸三氟硼酸钾,总收率74%,11BNMR(DMSO-d6,128MHz):0.48ppm。
实施例3:
苯硼酸三氟硼酸钾的合成:
氮气保护下,在100毫升三口瓶内,将联硼酸三氟硼酸钾(0.022摩尔)、溴苯(0.02摩尔)、1M碳酸钾溶液(0.04摩尔)和65毫升乙醇加入,搅拌均匀后,插通气管至溶液液面下,氮气鼓泡除氧约10-20分钟。随后将1.0%摩尔制备好的钯催化剂(苯乙胺、醋酸钯、叔丁醇钾和X-Phos反应后得到,制备方法参考:J.Am.Chem.Soc.,2010,132, 17701)氮气保护下加入,80oC反应过夜。检测反应结束后,硅藻土过滤。滤液减压高真空旋干,加入50毫升丙酮,过滤掉不溶性固体,滤液再次旋干(如不能旋干,可以加入甲苯后再次高真空旋蒸),加入20毫升甲基叔丁基醚打浆,过滤烘干,得到2.61克类白色片状固体,收率71%,HNMR与文献一致。
实施例4:
对甲苯硼酸三氟硼酸钾的合成:
氮气保护下,在100毫升三口瓶内,将联硼酸三氟硼酸钾(0.03摩尔),对溴甲苯(0.02摩尔)、1M氟化钾溶液(0.03摩尔)和45毫升二氧六环加入,搅拌均匀后,插通气管至溶液液面下,氮气鼓泡除氧约10-20分钟。随后将1.5%摩尔制备好的催化剂(苯乙胺、醋酸钯、叔丁醇钾和S-Phos反应后得到,制备方法参考J.Am.Chem.Soc.,2010, 132,17701)氮气保护下加入,100oC反应过夜。检测反应结束后,硅藻土过滤。滤液减压高真空旋干,加入70毫升丙酮,过滤掉不溶性固体,滤液再次旋干,加入25毫升乙醚后析出,过滤烘干,得到2.61克类白色片状固体,收率66%,HNMR与文献一致。
实施例5:
对醛基苯硼酸三氟硼酸钾的合成:
氮气保护下,在100毫升三口瓶内,将联硼酸三氟硼酸钾(0.03摩尔),对碘苯甲醛(0.02摩尔)、1M醋酸钾溶液(0.04摩尔)和70毫升乙醇加入,搅拌均匀后,插通气管至溶液液面下,氮气鼓泡除氧约10-20分钟。随后将2.0%摩尔制备好的催化剂[联苯-2-胺、Pd2(dba)3、叔丁醇钾和t -Bu3P反应后得到,制备方法参考J.Am.Chem.Soc.,2010, 132,17701]氮气保护下加入,80oC反应过夜。检测反应结束后,硅藻土过滤。滤液减压高真空旋干,加入40毫升丙酮,过滤掉不溶性固体,滤液再次旋干,加入15毫升甲基叔丁基醚打浆,过滤烘干,得到2.73克类白色片状固体,收率79%,HNMR与文献一致。
实施例6:
噻吩-3-硼酸三氟硼酸钾的合成:
氮气保护下,在100毫升三口瓶内,将联硼酸三氟硼酸钾(0.04摩尔)、3-氯噻吩(0.02摩尔)、1M磷酸钾溶液(0.06摩尔)和40毫升二甲基亚砜加入,搅拌均匀后,插通气管至溶液液面下,氮气鼓泡除氧约10-20分钟。随后将1.0%摩尔事先制备好的催化剂(联苯-2-胺、PdCl2(CH3CN)2、叔丁醇钾和X-Phos反应后得到,制备方法参考J.Am.Chem.Soc.,2010,132,17701)氮气保护下加入,100oC反应过夜。检测反应结束后,硅藻土过滤。滤液减压高真空旋干,加入40毫升丙酮,过滤掉不溶性固体,滤液再次旋干,加入25毫升乙醚打浆,过滤烘干,得到2.36克类白色片状固体,收率62%,HNMR与文献一致。
Claims (4)
1.一种合成芳基三氟硼酸钾的方法,其特征在于包括以下步骤:
第一步:氮气保护下,将甲醇和4-6当量氟氢化钾水溶液加入到四(烷氧基)联硼或四羟基联硼中,室温搅拌反应1-3小时,反应液静置,分出下层,旋干后,加入丙酮打浆,过滤,晾干后得到联硼酸三氟硼酸钾,产品为白色晶状固体,本步收率为62-85%;
所述四(烷氧基)联硼的制备方法如下:氮气保护下,四(四氢吡咯)联硼在4-50当量醇中回流反应,将生成的四氢吡咯蒸馏出来,随后减压蒸馏后,得到无色液体四(烷氧基)联硼;
所述四羟基联硼的制备方法如下:氮气保护下,四(四氢吡咯)联硼在4-50当量水中回流反应,蒸馏出四氢吡咯后,反应液降温,直接过滤得到白色固体四羟基联硼;
第二步:氮气保护下,将联硼酸三氟硼酸钾、芳基卤、催化剂、溶剂与无机碱水溶液混合,20~110℃反应过夜,检测反应结束后,硅藻土过滤,减压旋干反应液,加入丙酮后,过滤掉不溶性固体,滤液再次旋干,加入乙醚或甲基叔丁基醚打浆后得到芳基三氟硼酸钾,本步收率42-80%;
所述第二步中,芳基选自苯基或取代苯基、呋喃基或取代呋喃基、噻吩基或取代噻吩基、吡啶或取代吡啶基、吡唑基或取代吡唑基和恶唑或取代恶唑基、吲哚基或取代吲哚基、咔唑或取代咔唑、吲唑或取代吲唑;卤选自氯、溴或碘;
所述第二步中,催化剂需提前制备,选自Pd(OAc)2、Pd2(dba)3、PdCl2(CH3CN)2、PdCl2(PhCN)2与Cy3P、t -Bu3P、X-Phos、S-Phos和苯乙胺、联苯-2-胺三者任意组合反应;
所述第二步中,联硼酸三氟硼酸钾、芳基卤、钯催化剂、无机碱的摩尔比为1-2:1:0.01-0.03:1.5-3。
2.根据权利要求1所述一种合成芳基三氟硼酸钾的方法,其特征是:所述第一步醇选自:甲醇、乙醇或异丙醇。
3.根据权利要求1所述一种合成芳基三氟硼酸钾的方法,其特征是:所述第二步中,所述无机碱选自氟化钾、磷酸钾、碳酸钾或醋酸钾。
4.根据权利要求1所述一种合成芳基三氟硼酸钾的方法,其特征是:所述第二步中,溶剂选自甲醇、乙醇、异丙醇、四氢呋喃、二氧六环、二甲基亚砜或二甲基甲酰胺。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510321581.3A CN104945426B (zh) | 2015-06-12 | 2015-06-12 | 一种合成芳基三氟硼酸钾的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510321581.3A CN104945426B (zh) | 2015-06-12 | 2015-06-12 | 一种合成芳基三氟硼酸钾的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104945426A CN104945426A (zh) | 2015-09-30 |
CN104945426B true CN104945426B (zh) | 2017-01-25 |
Family
ID=54160543
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510321581.3A Active CN104945426B (zh) | 2015-06-12 | 2015-06-12 | 一种合成芳基三氟硼酸钾的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104945426B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108203440B (zh) * | 2016-12-19 | 2020-08-25 | 华东师范大学 | 芳基三氟硼酸钾的无溶剂双螺杆挤出连续合成工艺 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104203961B (zh) * | 2012-03-05 | 2017-05-17 | 泽维尔大学 | 作为用于治疗乳腺癌的基于硼的4‑羟基他莫昔芬和因多昔芬前药 |
CN104478912A (zh) * | 2014-12-20 | 2015-04-01 | 成都安斯利生物医药有限公司 | 一种制备饱和氮杂环三氟硼酸钾的方法 |
-
2015
- 2015-06-12 CN CN201510321581.3A patent/CN104945426B/zh active Active
Also Published As
Publication number | Publication date |
---|---|
CN104945426A (zh) | 2015-09-30 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN107011145A (zh) | 一种利用可见光催化制备2‑碘戊‑2‑烯‑1,4‑二酮衍生物的方法 | |
Ding et al. | Heterogeneous copper-catalyzed hydroxylation of aryl iodides under air conditions | |
CN106188116A (zh) | 一种合成吡唑‑4‑硼酸频那醇酯的方法 | |
Saunthwal et al. | Regioselective preferential CH activation of sterically hindered 1, 3-dienes over [4+ 2] cycloaddition | |
Zhou et al. | Nickel-catalyzed intramolecular desymmetrization addition of aryl halides to 1, 3-diketones | |
CN109320489A (zh) | 一种色烷类化合物及其制备方法 | |
Kitagaki et al. | Can the Crabbé Homologation Be Successfully Applied to the Synthesis of 1, 3-Disubstituted Allenes? | |
CN102079737A (zh) | 一种制备芹菜素的方法 | |
CN106478645B (zh) | 一种芳环取代的螺环吲哚二酮哌嗪类化合物及其合成方法 | |
CN104945426B (zh) | 一种合成芳基三氟硼酸钾的方法 | |
Li et al. | Palladium‐Catalyzed Double Suzuki Reactions: Synthesis of Dibenzo [4, 5: 6, 7] cyclohepta [1, 2, 3‐de] naphthalenes | |
Ying et al. | Nickel‐Catalyzed C− I‐Selective C (sp2)− C (sp3) Cross‐Electrophile Coupling of Bromo (iodo) arenes with Alkyl Bromides | |
CN104211723B (zh) | 乙烯基硼化试剂的合成及应用 | |
CN102887862A (zh) | 厄洛替尼的合成方法 | |
CN109879788B (zh) | 一种制备n-取代吲哚衍生物的方法 | |
CN104326893B (zh) | 侧链型二氟单体及其合成方法 | |
CN101717949B (zh) | 一种对乙烯基苯乙酸的制备方法 | |
CN108676171B (zh) | 一种具有橘红色荧光效应的烯烃铜配位聚合物及其制备方法 | |
CN106632440B (zh) | 一种芳基硼酸酯和烯基硼酸酯的制备方法 | |
CN104193596A (zh) | 反式邻羟基二苯乙烯衍生物及其制备方法和应用 | |
Xie et al. | A Straightforward and Practical Approach to Chiral Inducer:(2R, 3R)-1, 4-Dimethoxy-1, 1, 4, 4-tetraphenylbutane-2, 3-diol | |
Cavell et al. | Chiral N-heterocyclic carbene ligands based on a biisoquinoline template | |
CN110028470A (zh) | 一种利用二氧化碳生产脱氢乙酸和广藿香酮及其类似物的工艺方法 | |
CN110256492A (zh) | 一种含膦羧酸化合物及其制备方法 | |
CN104610002B (zh) | 一种芳香肼合成对称性联苯的方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |