CN105884808A - Preparation method of benzyl boron ester compound - Google Patents
Preparation method of benzyl boron ester compound Download PDFInfo
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- CN105884808A CN105884808A CN201610313077.3A CN201610313077A CN105884808A CN 105884808 A CN105884808 A CN 105884808A CN 201610313077 A CN201610313077 A CN 201610313077A CN 105884808 A CN105884808 A CN 105884808A
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- pinacol
- boric acid
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- benzyl
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- -1 benzyl boron ester compound Chemical class 0.000 title claims abstract description 63
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 238000006243 chemical reaction Methods 0.000 claims abstract description 87
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 claims abstract description 64
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims abstract description 60
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims abstract description 30
- 239000003960 organic solvent Substances 0.000 claims abstract description 30
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000004327 boric acid Substances 0.000 claims abstract description 20
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 238000010438 heat treatment Methods 0.000 claims description 51
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 49
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 48
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 29
- 238000000746 purification Methods 0.000 claims description 26
- 238000004440 column chromatography Methods 0.000 claims description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 24
- 239000003205 fragrance Substances 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 229910052796 boron Inorganic materials 0.000 claims description 9
- 239000002994 raw material Substances 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 230000006837 decompression Effects 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims 1
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 239000002304 perfume Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 23
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 abstract 1
- 239000003446 ligand Substances 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 92
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000003786 synthesis reaction Methods 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 24
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 150000001875 compounds Chemical class 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 239000007788 liquid Substances 0.000 description 22
- BMQDAIUNAGXSKR-UHFFFAOYSA-N (3-hydroxy-2,3-dimethylbutan-2-yl)oxyboronic acid Chemical compound CC(C)(O)C(C)(C)OB(O)O BMQDAIUNAGXSKR-UHFFFAOYSA-N 0.000 description 8
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- PLHBNAKJJQVXAX-UHFFFAOYSA-N OC(C)(C)C(C)(C)O.C(C1=CC=CC=C1)OB(O)O Chemical compound OC(C)(C)C(C)(C)O.C(C1=CC=CC=C1)OB(O)O PLHBNAKJJQVXAX-UHFFFAOYSA-N 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- CEBPNQDPRJUGGC-UHFFFAOYSA-N B(O)(O)O.COC1=CC=C(CCC(O)(C)C(C)(C)O)C=C1 Chemical compound B(O)(O)O.COC1=CC=C(CCC(O)(C)C(C)(C)O)C=C1 CEBPNQDPRJUGGC-UHFFFAOYSA-N 0.000 description 2
- OSALXNSWPLGWJO-UHFFFAOYSA-N B(O)(O)O.ClC1=CC=C(CCC(O)(C)C(C)(C)O)C=C1 Chemical compound B(O)(O)O.ClC1=CC=C(CCC(O)(C)C(C)(C)O)C=C1 OSALXNSWPLGWJO-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- RRCMGJCFMJBHQC-UHFFFAOYSA-N (2-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1Cl RRCMGJCFMJBHQC-UHFFFAOYSA-N 0.000 description 1
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
- DJGHSJBYKIQHIK-UHFFFAOYSA-N (3,5-dimethylphenyl)boronic acid Chemical compound CC1=CC(C)=CC(B(O)O)=C1 DJGHSJBYKIQHIK-UHFFFAOYSA-N 0.000 description 1
- AFSSVCNPDKKSRR-UHFFFAOYSA-N (3-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Br)=C1 AFSSVCNPDKKSRR-UHFFFAOYSA-N 0.000 description 1
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 1
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
- QWMJEUJXWVZSAG-UHFFFAOYSA-N (4-ethenylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=C)C=C1 QWMJEUJXWVZSAG-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- OQGUQRDSLVDCRT-UHFFFAOYSA-N (4-methylsulfanylphenoxy)boronic acid Chemical compound CSC1=CC=C(OB(O)O)C=C1 OQGUQRDSLVDCRT-UHFFFAOYSA-N 0.000 description 1
- MBYOBTPZNDJPCC-UHFFFAOYSA-N (4-phenylphenoxy)boronic acid Chemical compound C1=CC(OB(O)O)=CC=C1C1=CC=CC=C1 MBYOBTPZNDJPCC-UHFFFAOYSA-N 0.000 description 1
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- CQHNJWAZNZBMMO-UHFFFAOYSA-N B(O)(O)O.IC1=CC=CC=C1 Chemical compound B(O)(O)O.IC1=CC=CC=C1 CQHNJWAZNZBMMO-UHFFFAOYSA-N 0.000 description 1
- WGLKZASYUNTSEE-UHFFFAOYSA-N CC1(C)OB(Cc2cccc(OC(F)(F)F)c2)OC1(C)C Chemical compound CC1(C)OB(Cc2cccc(OC(F)(F)F)c2)OC1(C)C WGLKZASYUNTSEE-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- WGCWWEVNCDYERM-UHFFFAOYSA-N [3-(trifluoromethoxy)phenoxy]boronic acid Chemical compound OB(O)OC1=CC=CC(OC(F)(F)F)=C1 WGCWWEVNCDYERM-UHFFFAOYSA-N 0.000 description 1
- WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000003317 industrial substance Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- C07F5/04—Esters of boric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
The invention discloses a preparation method of a benzyl boron ester compound. According to the preparation method, aromatic boric acid Ar-B(OH)2, trimethyl silicon-based diazomethane, pinacol and tetrabutyl ammonium fluoride are subjected to a reaction in an organic solvent so as to obtain a benzyl pinacol boron ester compound, wherein Ar represents a non-heterocyclic aromatic group. After the method is adopted, the benzyl boron ester compound is obtained by starting from the aromatic boric acid and converting under a one-pot condition; the method is mild in reaction conditions, the reaction related to the method occurs smoothly in the air without needing strict water-free and oxygen-free conditions, and the method is convenient and simple to operate; the method has better tolerance and universality for functional groups and does not need an expensive metal catalyst and a ligand, thus being lower in reaction cost and being widely used for preparing the benzyl boron ester compound.
Description
Technical field
The invention belongs to organic synthesis field, particularly relate to the preparation method of a kind of benzyl boron ester compounds.
Background technology
Boron ester compounds is the industrial chemicals that a class is important, all has a wide range of applications in the middle of scientific research and commercial production.In scientific research, boron ester compounds, mainly as a class synthetic intermediate, is applied in transition metal-catalyzed cross-coupling reaction, for the target compound that construction structure is complex.In the middle of commercial production, boron ester compounds is obtained for is widely applied at medicine, pesticide and Material Field.All the time, the synthetic method of boron ester compounds is continuously improved and perfect by people, synthetic method about fragrance boron ester compounds is the most perfect at present, and the synthetic method for boron alkyl ester compounds particularly benzyl boron ester compounds then needs to be developed further.The method of traditional synthesis benzyl boron ester compounds mainly has two kinds: one, prepare corresponding lithium reagent from benzylic halides or grignard reagent reacts with boron ester and obtains benzyl boron ester compounds；Two, benzyl boron ester compounds is obtained by benzylic halides transition metal-catalyzed the reaction with connection boron ester down such as palladium, copper.But all there is certain shortcoming in these methods, such as the former needs the organometallic reagent using activity higher, and substrate functional group tolerance exists certain problem, and the latter then needs the transition-metal catalyst used costly, relatively costly, and the most friendly to environment.
Summary of the invention
It is an object of the invention to provide the preparation method of the benzyl boron ester compounds of a kind of simple to operate, mild condition, the method is from raw material simple and easy to get, realizing converting under conditions of transition metal-catalyzed, have and compare substrate universality widely, numerous benzyl boron ester compounds with different substituents can be synthesized by the method.
The technical scheme of the inventive method is as follows:
A kind of preparation method of benzyl boron ester compounds, including:
1) by fragrance boric acid (Ar-B (OH)2), trimethyl silicane base Azimethylene. and organic solvent be mixed and heated to raw material and disappear；
2) to step 1) product in be separately added into pinacol and tetrabutyl ammonium fluoride and continue heating, reaction obtain benzyl boron ester compounds.
Its reaction equation is as follows:
Wherein: the aromatic radical (Ar-) in described fragrance boric acid is non-heterocyclic aromatic base, and this aromatic radical can be substituted or unsubstituted aromatic radical (the most substituted or unsubstituted phenyl).
The method of the present invention has preferable tolerance to functional group, and the aromatic rings of fragrance boric acid can be substituted or unsubstituted phenyl ring or naphthalene nucleus.With one or more substituent groups, the position of substituent group can be not particularly limited on phenyl ring, common substituent group such as alkyl, thiazolinyl, aryl, alkoxyl, alkylthio group, trifluoromethyl and halogen etc..Can be with one or more in these substituent groups on described aromatic radical, when having multiple substituent group, these multiple substituent groups can be identical or different, and two adjacent substituent groups can separate or cyclization.
Abovementioned alkyl preferably has the alkyl of 1～4 carbon atom, such as methyl, the tert-butyl group.
Above-mentioned thiazolinyl preferred vinyl.
The preferred unsubstituted phenyl of aryl on above-mentioned aromatic rings.
The preferred methoxyl group of above-mentioned alkoxyl, trifluoromethoxy.
The preferred methyl mercapto of above-mentioned alkylthio group.
The preferred fluorine of above-mentioned halogen, chlorine, bromine or iodine atom.
Further, the preferred CH of the substituent group on aromatic radical3,tBu, CH=CH2, Ph, OMe, OCF3, SMe, CF3, F, Cl, Br or I.
The trimethyl silicane base Azimethylene. useful commercial reagent that the inventive method is used, it is not necessary to special handling, its consumption is 2～3 times of fragrance boric acid molal quantity.
The pinacol useful commercial reagent that the inventive method is used, it is not necessary to special handling, its consumption is 1～2 times of fragrance boric acid molal quantity.
The tetrabutyl ammonium fluoride useful commercial reagent that the inventive method is used, it is not necessary to special handling, its consumption is 0.5～1.5 times of fragrance boric acid molal quantity.
Four kinds of reactant molar ratios of the inventive method preferably fragrance boric acid: trimethyl silicane base Azimethylene.: pinacol: tetrabutyl ammonium fluoride=1: 2～3: 1.5: 1.
The organic solvent that the inventive method is used preferably is selected from the one in following collection: toluene, oxolane, 1,2-dichloroethanes, Isosorbide-5-Nitrae-dioxane.These organic solvents are also with commercial reagents, it is not necessary to special handling, and its consumption is preferably 1～5 milliliter/mmol fragrance boric acid.
Reaction temperature and the response time of above-mentioned reaction are slightly different according to different raw materials, with raw material detection disappearance be as the criterion, step 1) and 2) in heating-up temperature typically in the range of 40 DEG C～60 DEG C, the total time of heating is typically at 2～10 hours.Heating process can use oil bath (such as silicone oil, paraffin oil etc.) or other mode of heating.
The present invention carries out post processing to product the most after completion of the reaction, including concentrating and purification.
Described concentration process can use the method such as air-distillation, decompression distillation, such as, concentrate with rotavapor under vacuum.
Described purge process is to obtain pure product by the way of column chromatography, decompression distillation or recrystallization.
The inventive method achieves to convert under conditions of one pot from fragrance boric acid and obtain benzyl boron ester compounds, reaction condition is gentle, simple to operate, can be widely used for preparing benzyl boron ester compounds.Compared to the prior art, the present invention has a following advantage:
1, the reaction involved by the inventive method need not strict anhydrous and oxygen-free condition, can occur smoothly in atmosphere, easy to operate simply；
2, the reaction involved by the inventive method has preferable tolerance to functional group, and substituent group can be alkyl, thiazolinyl, aryl, alkoxyl, alkylthio group, trifluoromethyl and halogen (F, Cl, Br, I) etc.；
3, the reaction involved by the inventive method need not metallic catalyst and the part of costliness, can efficiently obtain various benzyl boron ester from raw material simple and easy to get, and reaction cost is relatively low.
Detailed description of the invention
Further describe the present invention below in conjunction with embodiment, but limit the scope of the present invention never in any form.
Embodiment 1
The synthesis of benzyl boric acid pinacol ester
To one equipped with the 10mL reaction tube of magneton adds phenylboric acid 49mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 4 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get benzyl boric acid pinacol ester by column chromatography purification, and its structure is shown below:
Under conditions above, productivity is 76%；
Other condition is constant, and when heating-up temperature is 40 DEG C, productivity is 50%；
Other condition is constant, and when heating-up temperature is 60 DEG C, productivity is 64%；
Other condition is constant, and when pinacol is 61mg (0.52mmol) (being dissolved in 1mL Isosorbide-5-Nitrae-dioxane), productivity is 56%；
Other condition is constant, and when being added without water, productivity is 61%；
Other condition is constant, and when being added without water and reaction dissolvent is oxolane, productivity is 24%；
Other condition is constant, and when being added without water and reaction dissolvent is 1, during 2-dichloroethanes, productivity is 29%；
Product benzyl boric acid pinacol ester is colourless liquid, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.26-7.20 (m, 2H), 7.18 (d, J=6.9Hz, 2H), 7.11 (t, J=7.1Hz, 1H), 2.29 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ138.7,129.0,128.3,124.8,83.4,24.7.
Embodiment 2
The synthesis of 4-methyl-benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-methylphenylboronic acid 54mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 3 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 47mg (0.4mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 3 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-methyl-benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 68%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.07 (d, J=8.2Hz, 2H), 7.04 (d, J=8.2Hz, 2H), 2.29 (s, 3H), 2.25 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ135.4,134.1,129.0,128.9,83.4,24.7,21.0.
Embodiment 3
The synthesis of 4-t-butylbenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-tert-butylbenzeneboronic acid 71mg (0.4mmol), trimethyl silicane
Base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), adds 1mL Isosorbide-5-Nitrae-dioxane, beyond the Great Wall rubber stopper toward system, reacts 4 hours on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 94mg (0.8mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.2mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-t-butylbenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 71%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.25 (d, J=8.1Hz, 2H), 7.11 (d, J=8.1Hz, 2H), 2.26 (s, 2H), 1.29 (s, 9H), 1.24 (s, 12H)；13C NMR(100MHz,CDCl3)δ147.5,135.4,128.7,125.2,83.4,34.2,31.4,24.8.
Embodiment 4
The synthesis of 4-methoxy-benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-methoxyphenylboronic acid 61mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 5 hours on the Electromagnetic Heating agitator of 60 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.6mL and 200uL water, continues reaction 5 hours on the Electromagnetic Heating agitator of 60 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-methoxy-benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 71%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.09 (d, J=8.5Hz, 2H), 6.79 (d, J=8.6Hz, 2H), 3.77 (s, 3H), 2.22 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ157.1,130.5,129.8,113.8,83.4,55.2,24.7.
Embodiment 5
The synthesis of 4-methylthiobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-methylthio phenyl boric acid 67mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.6mL (1.2mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 2 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.5mL and 200uL water, continues reaction 2 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-methylthiobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 55%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.16 (d, J=8.2Hz, 2H), 7.11 (d, J=8.2Hz, 2H), 2.45 (s, 3H), 2.25 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ135.9,134.0,129.5,127.4,83.5,24.7,16.5.
Embodiment 6
The synthesis of 4-luorobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-fluorobenzoic boric acid 56mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 1 hour on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 94mg (0.8mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 1 hour on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-luorobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 77%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.14-7.10(m,2H),6.95-6.87(m,2H),2.25(s,2H),1.23(s,12H)；13C NMR(100MHz,CDCl3) δ 160.8 (d, J=241.9Hz), 134.1 (d, J=3.1Hz), 130.2 (d, J=7.6Hz), 114.9 (d, J=21.2Hz), 83.5,24.7.
Embodiment 7
The synthesis of 4-chlorobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-chlorophenylboronic acid 62mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 2 hours on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.3mL and 200uL water, continues reaction 2 hours on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-chlorobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 85%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.19 (d, J=8.3Hz, 2H), 7.10 (d, J=8.3Hz, 2H), 2.25 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ137.2,130.6,130.3,128.3,83.6,24.7.
Embodiment 8
The synthesis of 4-bromobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-bromobenzeneboronic acid 80mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 3 hours on the Electromagnetic Heating agitator of 60 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 47mg (0.4mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 3 hours on the Electromagnetic Heating agitator of 60 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-bromobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 71%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.34 (d, J=8.3Hz, 2H), 7.05 (d, J=8.2Hz, 2H), 2.23 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ137.7,131.2,130.7,118.6,83.6,24.7.
Embodiment 9
The synthesis of 4-iodine benzyl boric acid pinacol ester
To one equipped with the 10mL reaction tube of magneton adds 4-iodobenzene boric acid 99mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 4 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.2mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-iodine benzyl boric acid pinacol ester by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 56%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.54 (d, J=8.3Hz, 2H), 6.93 (d, J=8.3Hz, 2H), 2.22 (s, 2H), 1.22 (s, 12H)；13C NMR(100MHz,CDCl3)δ138.4,137.2,131.2,89.7,83.6,24.7.
Embodiment 10
The synthesis of 4-phenylbenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-phenyl phenylboric acid 79mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 5 hours on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1.5mL 1,4-dioxane) 47mg (0.4mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.5mL and 200uL water, continues reaction 5 hours on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-phenylbenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is white solid, and productivity is 86%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.58 (d, J=7.8Hz, 2H), 7.48 (d, J=8.0Hz, 2H), 7.41 (t, J=7.6Hz, 2H), 7.30 (t, J=7.7Hz, 1H), 7.27-7.24 (m, 2H), 2.34 (s, 2H), 1.25 (s, 12H)；13C NMR(100MHz,CDCl3)δ141.3,137.8,137.8,129.4,128.7,127.0,126.9,126.8,83.5,24.8.
Embodiment 11
The synthesis of 4-vinyl benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 4-vinylphenylboronic acid 59mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 4 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.3mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 4-vinyl benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 50%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.29 (d, J=8.1Hz, 2H), 7.14 (d, J=8.0Hz, 2H), 6.67 (dd, J=17.6,10.9Hz, 1H), 5.67 (d, J=17.6Hz, 1H), 5.15 (d, J=10.9Hz, 1H), 2.28 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ138.5,136.8,134.3,129.1,126.2,112.4,83.5,24.7.
Embodiment 12
The synthesis of 3-methyl-benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-methylphenylboronic acid 54mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 2 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 94mg (0.8mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 2 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-methyl-benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 83%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.12 (t, J=7.4Hz, 1H), 6.98 (d, J=7.9Hz, 2H), 6.93 (d, J=7.4Hz, 1H), 2.30 (s, 3H), 2.25 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ138.4, 137.6,129.8,128.1,125.9,125.6,83.3,24.7,21.3.
Embodiment 13
The synthesis of 3-methoxy-benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-methoxyphenylboronic acid 61mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 5 hours on the Electromagnetic Heating agitator of 60 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.6mL and 200uL water, continues reaction 5 hours on the Electromagnetic Heating agitator of 60 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-methoxy-benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 74%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.15 (t, J=7.9Hz, 1H), 6.79-6.73 (m, 2H), 6.67 (dd, J=8.2,2.4Hz, 1H), 3.78 (s, 3H), 2.27 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ159.5,140.2,129.2,121.5,114.6,110.4,83.5,55.1,24.7.
Embodiment 14
The synthesis of 3-trifluoro-methoxybenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-trifluoromethoxy phenylboric acid 82mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 1 hour on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.2mL and 200uL water, continues reaction 1 hour on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-trifluoro-methoxybenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 70%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.26-7.21 (m, 1H), 7.12-7.05 (m, 2H), 6.97 (d, J=8.1Hz, 1H), 2.31 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3) δ 149.2,141.0,129.4,127.5,121.5,120.5 (q, J=256.7Hz), 117.4,83.6,24.7.
Embodiment 15
The synthesis of 3-chlorobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-chlorophenylboronic acid 62mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 2 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 94mg (0.8mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 2 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-chlorobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 42%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.17 (s, 1H), 7.14 (d, J=7.6Hz, 1H), 7.09 (d, J=8.2Hz, 1H), 7.05 (d, J=7.4Hz, 1H), 2.26 (s, 2H), 1.23 (s, 12H)；13C NMR(100MHz,CDCl3)δ140.8,133.9,129.4,129.1,127.2,125.1,83.6,24.7.
Embodiment 16
The synthesis of 3-bromobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-bromobenzeneboronic acid 80mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 3 hours on the Electromagnetic Heating agitator of 60 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 47mg (0.4mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.3mL and 200uL water, continues reaction 3 hours on the Electromagnetic Heating agitator of 60 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-bromobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 41%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.33(s,1H),7.26-7.22(m,1H),7.12-7.07(m,2H),2.26(s,2H),1.23(s,12H)；13C NMR(100MHz,CDCl3)δ141.1,132.0,129.7,128.0,127.7,122.3,83.6,24.7.
Embodiment 17
The synthesis of 3-trifluoromethyl benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3-trifluoromethylbenzene boronic acid 76mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 3 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.5mL and 200uL water, continues reaction 3 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3-trifluoromethyl benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 72%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.44(s,1H),7.39-7.31(m,3H),2.35(s,2H),1.23(s,12H)；13C NMR(100MHz,CDCl3) δ 139.7,132.4,130.4 (q, J=31.7Hz), 128.6,125.7 (q, J=3.6Hz), 124.4 (q, J=270.0Hz), 121.8 (q, J=3.9Hz), 83.7,24.7.
Embodiment 18
The synthesis of 2-methyl-benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 2-methylphenylboronic acid 54mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.6mL (1.2mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 1 hour on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 1 hour on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 2-methyl-benzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 54%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.14-7.01(m,4H),2.27(s,3H),2.25(s,2H),1.22(s,12H)；13C NMR(100MHz,CDCl3)δ137.5,135.9,129.7,129.4,125.8,125.1,83.3,24.7,20.1.
Embodiment 19
The synthesis of 2-luorobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 2-fluorobenzoic boric acid 56mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.6mL (1.2mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 4 hours on the Electromagnetic Heating agitator of 60 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 47mg (0.4mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.6mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 60 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 2-luorobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 81%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.19 (t, J=7.5Hz, 1H), 7.11 (dd, J=13.7,6.6Hz, 1H), 7.04-6.95 (m, 2H), 2.26 (s, 2H), 1.24 (s, 12H)；13C NMR(100MHz,CDCl3) δ 161.0 (d, J=243.6Hz), 131.3 (d, J=5.0Hz), 126.6 (d, J=8.0Hz), 126.0 (d, J=16.7Hz), 123.8 (d, J=3.6Hz), 114.9 (d, J=22.2Hz), 83.6,24.7.
Embodiment 20
The synthesis of 2-chlorobenzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 2-chlorophenylboronic acid 62mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.6mL (1.2mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 3 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.2mL and 200uL water, continues reaction 3 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 2-chlorobenzyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 68%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 7.30 (dd, J=7.8,1.4Hz, 1H), 7.22 (dd, J=7.5,1.6Hz, 1H), 7.14 (td, J=7.4,1.4Hz, 1H), 7.07 (td, J=7.6,1.8Hz, 1H), 2.38 (s, 2H), 1.24 (s, 12H)；13C NMR(100MHz,CDCl3)δ137.5,133.9,130.8,129.0,126.7,126.5,83.6,24.7.
Embodiment 21
The synthesis of 1-menaphthyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 1-naphthalene boronic acids 69mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.5mL (1.0mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 5 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 94mg (0.8mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.4mL and 200uL water, continues reaction 5 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 1-menaphthyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 43%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3) δ 8.00 (d, J=7.8Hz, 1H), 7.84-7.79 (m, 1H), 7.65 (d, J=7.5Hz, 1H), 7.50-7.42 (m, 2H), 7.36 (q, J=7.1Hz, 2H), 2.69 (s, 2H), 1.19 (s, 12H)；13C NMR(100MHz,CDCl3)δ135.6,133.8,132.5,128.5,126.5,125.8,125.4,125.3,124.5,83.5,24.7.
Embodiment 22
The synthesis of 2-menaphthyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 2-naphthalene boronic acids 69mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.5mL (1.0mmol), 1mL toluene is added toward system, rubber stopper beyond the Great Wall, reacts 4 hours on the Electromagnetic Heating agitator of 40 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.3mL and 200uL water, continues reaction 4 hours on the Electromagnetic Heating agitator of 40 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 2-menaphthyl pinacol borate by column chromatography purification, and its structure is shown below:
This compound is colourless liquid, and productivity is 44%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ7.78-7.71(m,3H),7.61(s,1H),7.43-7.32(m,3H),2.45(s,2H),1.23(s,12H)；13C NMR(100MHz,CDCl3)δ136.3,133.8,131.5,128.2,127.7,127.6,127.3,126.6,125.7,124.7,83.5,24.7.
Embodiment 23
The synthesis of 3,5-dimethyl benzyl pinacol borate
To one equipped with the 10mL reaction tube of magneton adds 3,5-dimethylphenyl boronic acid 60mg (0.4mmol), trimethyl silicane base Azimethylene. (2M hexane solution) 0.4mL (0.8mmol), 1mL 1 is added toward system, 4-dioxane, rubber stopper beyond the Great Wall, reacts 2 hours on the Electromagnetic Heating agitator of 50 DEG C.It is separately added into pinacol subsequently and (is dissolved in 1mL 1,4-dioxane) 71mg (0.6mmol), tetrabutyl ammonium fluoride (1M tetrahydrofuran solution) 0.5mL and 200uL water, continues reaction 2 hours on the Electromagnetic Heating agitator of 50 DEG C.Reaction utilizes Rotary Evaporators to be removed by organic solvent after terminating, and i.e. can get 3 by column chromatography purification, 5-dimethyl benzyl pinacol borate, and its structure is shown below:
This compound is colourless liquid, and productivity is 78%, and its nuclear magnetic data is as follows:
1H NMR(400MHz,CDCl3)δ6.80(s,2H),6.76(s,1H),2.26(s,6H),2.21(s,2H),1.23(s,12H)；13C NMR(100MHz,CDCl3)δ138.4,137.6,126.9,126.6,83.4,24.7,21.3。
Claims (10)
1. a preparation method for benzyl boron ester compounds, including:
1) fragrance boric acid, trimethyl silicane base Azimethylene. with organic solvent, are mixed and heated to raw material and disappear；
2) to step 1) product in be separately added into pinacol and tetrabutyl ammonium fluoride and continue heating, reaction obtain benzyl
Base pinacol boron ester compounds.
2. preparation method as claimed in claim 1, it is characterised in that the aromatic radical in described fragrance boric acid represents non-heterocycle virtue
Perfume base, on it without or with one or more substituent groups.
3. preparation method as claimed in claim 2, it is characterised in that described substituent group is selected from alkyl, thiazolinyl, aryl, alkane
One or more in epoxide, alkylthio group, trifluoromethyl and halogen, when with multiple substituent group, these multiple replacements
Base is identical or different, and two adjacent substituent groups are separate or cyclization.
4. preparation method as claimed in claim 1, it is characterised in that described organic solvent selected from toluene, oxolane, 1,2-
One in dichloroethanes and 1,4-dioxane.
5. preparation method as claimed in claim 1, it is characterised in that step 1) described in the use of trimethyl silicane base Azimethylene.
Amount is 2～3 times of fragrance boric acid molal quantity, and the consumption of described organic solvent is 1～5 milliliter/mmol fragrance boric acid.
6. preparation method as claimed in claim 1, it is characterised in that step 2) described in the consumption of pinacol be fragrant boric acid
1～2 times of molal quantity, the consumption of described tetrabutyl ammonium fluoride is 0.5～1.5 times of fragrance boric acid molal quantity.
7. preparation method as claimed in claim 1, it is characterised in that the molar ratio of four kinds of reactants is fragrance boric acid:
Trimethyl silicane base Azimethylene.: pinacol: tetrabutyl ammonium fluoride=1:2～3:1.5:1.
8. preparation method as claimed in claim 1, it is characterised in that step 1) and 2) in heating-up temperature be 40～60 DEG C.
9. preparation method as claimed in claim 1, it is characterised in that also include: after having reacted, product is carried out dense
Contracting and purification.
10. preparation method as claimed in claim 9, it is characterised in that product is carried out dense by normal pressure or decompression distillation
Contracting, enriched product carries out decompression distillation after column chromatography again and obtains the product of purification.
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| CN110605143A (en) * | 2017-10-27 | 2019-12-24 | 苏州大学 | Application of organic iron salt as catalyst in synthesis of alkyl boron ester compound |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150361109A1 (en) * | 2014-06-16 | 2015-12-17 | Dow Agrosciences Llc | Methods for producing borylated arenes |
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2016
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150361109A1 (en) * | 2014-06-16 | 2015-12-17 | Dow Agrosciences Llc | Methods for producing borylated arenes |
Non-Patent Citations (1)
| Title |
|---|
| WU C Q. ET AL: ""One-carbon homologation of arylboronic acids: a convenient approach to the synthesis of pinacol benzylboronates"", 《ORG. CHEM. FRONT》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110605143A (en) * | 2017-10-27 | 2019-12-24 | 苏州大学 | Application of organic iron salt as catalyst in synthesis of alkyl boron ester compound |
| CN110605143B (en) * | 2017-10-27 | 2022-07-19 | 苏州大学 | Application of organic iron salt as catalyst in synthesis of alkyl boron ester compound |
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