WO2020118922A1 - 基于锂化合物制备硼酸酯的方法 - Google Patents
基于锂化合物制备硼酸酯的方法 Download PDFInfo
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- WO2020118922A1 WO2020118922A1 PCT/CN2019/077386 CN2019077386W WO2020118922A1 WO 2020118922 A1 WO2020118922 A1 WO 2020118922A1 CN 2019077386 W CN2019077386 W CN 2019077386W WO 2020118922 A1 WO2020118922 A1 WO 2020118922A1
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- Prior art keywords
- acid
- lithium
- reaction
- mmol
- minutes
- Prior art date
Links
- -1 boric acid ester Chemical class 0.000 title claims abstract description 106
- 150000002642 lithium compounds Chemical class 0.000 title claims abstract description 53
- 238000000034 method Methods 0.000 title claims abstract description 19
- 239000004327 boric acid Substances 0.000 title claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims abstract description 184
- 239000002904 solvent Substances 0.000 claims abstract description 101
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000012298 atmosphere Substances 0.000 claims abstract description 58
- 239000011261 inert gas Substances 0.000 claims abstract description 58
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims abstract description 38
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 38
- 229910000085 borane Inorganic materials 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- SDYMNZGECSEJAD-UHFFFAOYSA-N [Li].COC1=CC=CC=C1N Chemical compound [Li].COC1=CC=CC=C1N SDYMNZGECSEJAD-UHFFFAOYSA-N 0.000 claims abstract description 11
- NUZZTIFRAVGNIM-UHFFFAOYSA-N COC1=CC=C(N)C=C1.[Li] Chemical compound COC1=CC=C(N)C=C1.[Li] NUZZTIFRAVGNIM-UHFFFAOYSA-N 0.000 claims abstract description 10
- PLJMCNOKGFAGSG-UHFFFAOYSA-N 2,6-di(propan-2-yl)aniline;lithium Chemical compound [Li].CC(C)C1=CC=CC(C(C)C)=C1N PLJMCNOKGFAGSG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 93
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical group CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 claims description 61
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 53
- 239000000741 silica gel Substances 0.000 claims description 53
- 229910002027 silica gel Inorganic materials 0.000 claims description 53
- 229910052744 lithium Inorganic materials 0.000 claims description 50
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 36
- 238000006197 hydroboration reaction Methods 0.000 claims description 34
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 26
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 24
- 238000004440 column chromatography Methods 0.000 claims description 23
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 claims description 20
- ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 claims description 18
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 18
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 claims description 18
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 18
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 claims description 15
- 239000005711 Benzoic acid Substances 0.000 claims description 13
- 235000010233 benzoic acid Nutrition 0.000 claims description 13
- JZJLUBFYXQAMFA-UHFFFAOYSA-N [Li].CC1=C(N)C=CC=C1 Chemical compound [Li].CC1=C(N)C=CC=C1 JZJLUBFYXQAMFA-UHFFFAOYSA-N 0.000 claims description 12
- HONSQGQZJYOWBH-UHFFFAOYSA-N lithium;4-methylaniline Chemical compound [Li].CC1=CC=C(N)C=C1 HONSQGQZJYOWBH-UHFFFAOYSA-N 0.000 claims description 12
- OFJWFSNDPCAWDK-UHFFFAOYSA-N 2-phenylbutyric acid Chemical compound CCC(C(O)=O)C1=CC=CC=C1 OFJWFSNDPCAWDK-UHFFFAOYSA-N 0.000 claims description 10
- SEENCYZQHCUTSB-UHFFFAOYSA-N 5-bromo-2-methylbenzoic acid Chemical compound CC1=CC=C(Br)C=C1C(O)=O SEENCYZQHCUTSB-UHFFFAOYSA-N 0.000 claims description 10
- XRXMNWGCKISMOH-UHFFFAOYSA-N 2-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Br XRXMNWGCKISMOH-UHFFFAOYSA-N 0.000 claims description 9
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 claims description 9
- BBYDXOIZLAWGSL-UHFFFAOYSA-N 4-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1 BBYDXOIZLAWGSL-UHFFFAOYSA-N 0.000 claims description 9
- GHICCUXQJBDNRN-UHFFFAOYSA-N 4-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(I)C=C1 GHICCUXQJBDNRN-UHFFFAOYSA-N 0.000 claims description 9
- KDVYCTOWXSLNNI-UHFFFAOYSA-N 4-t-Butylbenzoic acid Chemical compound CC(C)(C)C1=CC=C(C(O)=O)C=C1 KDVYCTOWXSLNNI-UHFFFAOYSA-N 0.000 claims description 9
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 9
- 239000001361 adipic acid Substances 0.000 claims description 9
- 235000011037 adipic acid Nutrition 0.000 claims description 9
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 9
- ZHQLTKAVLJKSKR-UHFFFAOYSA-N homophthalic acid Chemical compound OC(=O)CC1=CC=CC=C1C(O)=O ZHQLTKAVLJKSKR-UHFFFAOYSA-N 0.000 claims description 9
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 9
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 9
- 229940005605 valeric acid Drugs 0.000 claims description 9
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 claims description 8
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 claims description 7
- 150000003931 anilides Chemical class 0.000 claims description 6
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 abstract description 6
- 229910052796 boron Inorganic materials 0.000 abstract description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 150000002148 esters Chemical class 0.000 abstract description 2
- 238000005984 hydrogenation reaction Methods 0.000 abstract 4
- MYSVRTQAMRATFT-UHFFFAOYSA-N 2,6-dimethylaniline;lithium Chemical compound [Li].CC1=CC=CC(C)=C1N MYSVRTQAMRATFT-UHFFFAOYSA-N 0.000 abstract 1
- 150000001298 alcohols Chemical class 0.000 abstract 1
- CJRILLVXZDAQBZ-UHFFFAOYSA-N aniline;lithium Chemical compound [Li].NC1=CC=CC=C1 CJRILLVXZDAQBZ-UHFFFAOYSA-N 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 228
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 102
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 81
- 238000005481 NMR spectroscopy Methods 0.000 description 67
- 238000005160 1H NMR spectroscopy Methods 0.000 description 66
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 47
- 230000018044 dehydration Effects 0.000 description 34
- 238000006297 dehydration reaction Methods 0.000 description 34
- 238000006392 deoxygenation reaction Methods 0.000 description 34
- CRUILBNAQILVHZ-UHFFFAOYSA-N 1,2,3-trimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1OC CRUILBNAQILVHZ-UHFFFAOYSA-N 0.000 description 22
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- 239000000203 mixture Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 229940030010 trimethoxybenzene Drugs 0.000 description 11
- 150000001735 carboxylic acids Chemical class 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 235000010338 boric acid Nutrition 0.000 description 7
- 229960002645 boric acid Drugs 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QVXCVTFQUXXVNO-UHFFFAOYSA-N C(C)(C)C1=C(NC(C[Li])=CC(C)NC2=C(C=CC=C2C(C)C)C(C)C)C(=CC=C1)C(C)C Chemical compound C(C)(C)C1=C(NC(C[Li])=CC(C)NC2=C(C=CC=C2C(C)C)C(C)C)C(=CC=C1)C(C)C QVXCVTFQUXXVNO-UHFFFAOYSA-N 0.000 description 5
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 4
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052761 rare earth metal Inorganic materials 0.000 description 4
- 150000002910 rare earth metals Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- JDFVKVHWIJWWOM-UHFFFAOYSA-N lithium;[2,6-di(propan-2-yl)phenyl]azanide Chemical compound [Li+].CC(C)C1=CC=CC(C(C)C)=C1[NH-] JDFVKVHWIJWWOM-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007866 anti-wear additive Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000003254 gasoline additive Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- BITPAXWTJXOWKL-UHFFFAOYSA-N lithium;oxolane Chemical compound [Li].C1CCOC1 BITPAXWTJXOWKL-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000003879 lubricant additive Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- WWYDYZMNFQIYPT-UHFFFAOYSA-N ru78191 Chemical compound OC(=O)C(C(O)=O)C1=CC=CC=C1 WWYDYZMNFQIYPT-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals 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
- C07F5/04—Esters of boric acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0252—Nitrogen containing compounds with a metal-nitrogen link, e.g. metal amides, metal guanidides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/12—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing organo-metallic compounds or metal hydrides
- B01J31/122—Metal aryl or alkyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/095—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of organic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/12—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of mineral acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/26—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
Definitions
- the invention relates to the application of a commercial reagent lithium compound, in particular to a method for preparing a borate based on a lithium compound.
- the organoborate can be regarded as a derivative in which hydrogen in orthoboric acid B(OH) 3 is replaced by an organic group, and in addition, metaborate (ROBO) 3 . Because of its stability and low toxicity, borate is widely used in various fields. It is a main raw material for the synthesis of boron-containing compounds. Borate ester compounds can be used not only as rust inhibitors, preservatives, polymer additives, anti-wear additives, automotive brake fluids, gasoline additives, flame retardants in cleaning agents, but also as lubricant additives.
- LiAlH 4 and NaBH 4 systems have a high safety risk.
- the SmI 2 -H 2 O-Et 3 N system requires a lot of reagents, and the transition metal complex system needs to be carried out under high temperature and high pressure
- the catalytic reaction requires a reaction temperature of 60°C and a reaction time of 24 hours.
- the difference between the nucleophilic addition reaction of carboxylic acid and aldehyde and ketone (1) The active hydrogen of carboxylic acid is easy to leave, so its two O are actually equivalent, so from the perspective of spatial structure, the steric hindrance of carboxyl group Large, and the presence of carboxyl hydrogen bonds makes the density of the electron cloud of the entire carbonyl group larger, and it is more difficult for the nucleophile to attack the active center; (2) The nucleophile advances to attack the carbonyl carbon. Small advanced attacks, such as aldehydes and ketones have a lower electron cloud density than esters and amides, so they have high activity and will preferentially react.
- the purpose of the invention of the present invention is to provide a method for preparing boronate esters by borohydration of carboxylic acids, that is, lithium compounds are used as high-efficiency catalysts to catalyze the borohydration reaction of carboxylic acids and borane, carboxylic acids are generally solid, carboxylic acids and pinacol The reaction of borane is a heterogeneous reaction.
- a method for preparing a boric acid ester based on a lithium compound includes the steps of mixing borane and carboxylic acid under an inert gas atmosphere, then adding a catalyst lithium compound, and then performing a hydroboration reaction to obtain a boric acid ester; the lithium compound is positive Butyl lithium, lithium anilide, lithium p-toluidine, lithium o-toluidine, lithium 2-methoxyaniline, lithium 4-methoxyaniline, 2,6,-dimethylaniline Lithium or lithium 2,6-diisopropylaniline.
- a method for preparing an alcohol compound based on a lithium compound includes the steps of mixing borane and carboxylic acid under an inert gas atmosphere, then adding a catalyst lithium compound, and then performing a hydroboration reaction; adding silica gel and methanol after the hydroboration reaction is completed , Carrying out a hydrolysis reaction to obtain an alcohol compound;
- the lithium compound is n-butyllithium, anilide lithium, p-toluidine lithium, o-toluidine lithium, 2-methoxyaniline lithium, 4-methoxy Anilide lithium, 2,6,-dimethylaniline lithium or 2,6-diisopropylaniline lithium.
- lithium compound in catalyzing borohydride reaction of carboxylic acid and borane; the lithium compound is n-butyl lithium, lithium anilide, lithium p-toluidine, lithium o-toluidine, 2-methoxyaniline Lithium, 4-methoxyaniline lithium, 2,6,-dimethylaniline lithium or 2,6-diisopropylaniline lithium.
- the lithium compound is a commercial lithium compound reagent.
- the borane is pinacol borane;
- the carboxylic acid is acetic acid, hexanoic acid, valeric acid, heptanoic acid, trimethylacetic acid, adipic acid, benzoic acid, 4-bromobenzoic acid, 4-fluorobenzoic acid, 1-naphthoic acid, 2-methoxybenzoic acid, o-carboxyphenylacetic acid, 3-indoleacetic acid, 2-phenylbutyric acid, 2-methyl-5-bromo-benzoic acid, 4 -Tert-butylbenzoic acid, 2-bromobenzoic acid, 4-iodobenzoic acid, 3-phenylpropionic acid, diphenylacetic acid, etc.
- the molar ratio of the carboxylic acid and the borane is 1:3 to 1:7.
- the temperature of the hydroboration reaction is room temperature
- the time is 10 to 80 minutes
- the amount of the lithium compound is 0.1% to 0.9% of the molar amount of the carboxylic acid.
- the lithium compound is n-butyl lithium
- the carboxylic acid is benzoic acid, 4-bromobenzoic acid, 4-fluorobenzoic acid, 1-naphthoic acid, 2-methoxybenzoic acid, o-carboxyphenylacetic acid, 3-indene Indoacetic acid, 2-phenylbutyric acid, 2-methyl-5-bromo-benzoic acid, 4-tert-butylbenzoic acid, 2-bromobenzoic acid, 4-iodobenzoic acid, 3-phenylpropionic acid or diphenyl
- the temperature of the hydroboration reaction is room temperature
- the time is 40-50 minutes
- the amount of the lithium compound is 0.4%-0.6% of the molar amount of carboxylic acid.
- the lithium compound is lithium anilide, lithium p-toluidine, lithium o-toluidine, lithium 2-methoxyaniline, lithium 4-methoxyaniline, 2,6,-dimethyl Lithium anilide or lithium 2,6-diisopropylaniline, carboxylic acids are benzoic acid, 4-bromobenzoic acid, 4-fluorobenzoic acid, 1-naphthoic acid, 2-methoxybenzoic acid, o-carboxybenzene Acetic acid, 3-indoleacetic acid, 2-phenylbutyric acid, 2-methyl-5-bromo-benzoic acid, 4-tert-butylbenzoic acid, 2-bromobenzoic acid, 4-iodobenzoic acid, 3-benzene
- the temperature of the hydroboration reaction is room temperature
- the time is 70 to 80 minutes
- the amount of the lithium compound is 0.7% to 0.9% of the molar amount of the
- the temperature of the hydroboration reaction is room temperature and the time is 10-20 Min
- the amount of n-butyllithium is 0.1% to 0.3% of the molar amount of carboxylic acid
- the lithium compound is lithium anilide, lithium p-toluidine, lithium o-toluidine, 2-methoxyaniline Lithium, 4-methoxyaniline lithium, 2,6,-dimethylaniline lithium or 2,6-diisopropylaniline lithium
- carboxylic acid is acetic acid, hexanoic acid, valeric acid, heptanoic acid
- the time is 50 to 60 minutes
- the reaction is terminated by contacting with air, the solvent is removed under reduced pressure, and then silica gel and methanol are added; after the hydrolysis reaction is completed, the solvent is removed under reduced pressure, and then the column compound is used to obtain the alcohol compound.
- the dosage ratio of carboxylic acid to silica gel and methanol is 1mmoL: 2 ⁇ 2.2g: 6mL; preferably, when the carboxylic acid is acetic acid, hexanoic acid, valeric acid, heptanoic acid, trimethyl acetic acid or adipic acid ,
- the dosage ratio of carboxylic acid to silica gel and methanol is 1mmoL: 2.2g: 6mL;
- carboxylic acid is benzoic acid, 4-bromobenzoic acid, 4-fluorobenzoic acid, 1-naphthoic acid, 2-methoxybenzoic acid, ortho Carboxyphenylacetic acid, 3-indoleacetic acid, 2-phenylbutyric acid, 2-methyl-5-bromo-benzoic acid, 4-tert-butylbenzoic acid, 2-bromobenzoic acid, 4-iodobenzoic acid, 3 -When phenylpropionic acid or diphenylacetic
- the hydrolysis reaction is carried out at 50°C for 115 to 120 minutes; preferably, when the carboxylic acid is acetic acid, hexanoic acid, valeric acid, heptanoic acid, trimethylacetic acid or adipic acid, the hydrolysis reaction is at 50°C Reaction for 115 minutes; carboxylic acids are benzoic acid, 4-bromobenzoic acid, 4-fluorobenzoic acid, 1-naphthoic acid, 2-methoxybenzoic acid, o-carboxyphenylacetic acid, 3-indoleacetic acid, 2-phenyl Butyric acid, 2-methyl-5-bromo-benzoic acid, 4-tert-butylbenzoic acid, 2-bromobenzoic acid, 4-iodobenzoic acid, 3-phenylpropionic acid or diphenylacetic acid, the hydrolysis reaction is The reaction was carried out at 50°C for 120 minutes.
- borane and carboxylic acid are mixed, and then the lithium compound of the catalyst is added, and then the borohydride reaction is carried out; after the reaction is completed, the reaction is stopped by contact with air, and the solvent is removed under reduced pressure to obtain different substituted borate esters.
- the inert gas atmosphere can be realized in the glove box, which is a conventional technique.
- borane and carboxylic acid are mixed under an inert gas atmosphere, and then a lithium compound of the catalyst is added, and then the borohydride reaction is carried out. After the reaction is completed, the reaction is terminated by contact with air. After removing the solvent under reduced pressure, silica gel and methanol are added to hydrolyze the reaction The alcohol compound is obtained.
- the inert gas atmosphere can be realized in the glove box, which is a conventional technique.
- the present invention has the following advantages compared with the prior art:
- the present invention finds for the first time that commercial lithium compounds can efficiently catalyze the borohydride reaction between carboxylic acid and borane, which is highly compatible with the economic synthesis of atoms.
- the lithium compound disclosed in the present invention catalyzes the borohydration reaction of carboxylic acid and borane with high catalytic activity (the amount of lithium compound used is 0.1% to 0.9% of the molar amount of carboxylic acid), the reaction conditions are mild (room temperature), and the reaction time is short (10 ⁇ 50 minutes), and the reaction yield is high, the reaction is simple and controllable, and the post-treatment is simple.
- the lithium compound catalyzed by the lithium compound disclosed in the present invention has a wide range of applications for substrates, and is suitable for carboxylic acids with different substituent positions and different electronic effects, providing more choices for the industrial synthesis of borate esters; and
- the reaction process is simple and controllable, the yield is high, the product post-processing is easy, and it is suitable for industrial production.
- FIG. 1 is a schematic diagram of the reaction in Example 1;
- Fig. 2 is the chemical structural formula of the comparative example 2,4-bis(2,6-diisopropylanilino)-2-pentenyl lithium.
- the calculated 1 H yield is 97%, and the NMR data of the product borate: 1 H NMR (400 MHz, CDCl 3 ): ⁇ 7.22– 7.32 (m, 5H, ArH), 4.92 (s, 2H, CH 2 ) , 1.26 (s, 36H, CH 3 ); when the amount of pinacol borane is 2 mmol, the product yield is 99%; when the amount of pinacol borane is 361.2 ⁇ L, 2.5 mmol, the product yield is 99%. If the lithium compound is replaced with the triaryloxy rare earth catalyst Nd(OAr) 3 (THF) 2 , the product cannot be obtained.
- the calculated 1H yield is 12%.
- NMR data of the product 1H NMR (400 MHz, CDCl3): ⁇ 7.22– 7.32 (m, 5H, ArH), 4.92 (s, 2H, CH2), 1.26 (s, 36H, CH3).
- Acetic acid 28.6 ⁇ L, 0.5 mmol was used as the raw material, with a yield of 18%.
- diphenylacetic acid 105.8 mg, 0.5 mmol, pinacol borane (289 ⁇ L, 2 mmol) was added to the reaction flask after dehydration and deoxygenation treatment, and finally n-butyl was added Lithium (0.5 mol% amount) in tetrahydrofuran solution, react at room temperature for 45 minutes, the reaction solution is exposed to air, the solvent is removed, to obtain the product borate ester, with trimethoxybenzene (83.84 mg, 0.5 mmol) as internal standard, dissolved with CDCl3, stirred for 10 minutes, sampled, and equipped with NMR. The calculated 1H yield is 99%.
- NMR data of the product 1H NMR (400 MHz, CDCl3): ⁇ 7.16 (t, 2H, ,ArCH), 7.03- 7.08 (m, 3H, ArCH), 3.78 (t, 2H, CH2, OCH2), 2.60 (t, 2H, CH2), 1.74-1.81 (m, 2H, CH2), 1.15 (s, 36H, CH3).
- diphenylacetic acid 105.8 mg, 0.5 mmol, pinacol borane (289 ⁇ L, 2 mmol) was added to the reaction flask after dehydration and deoxygenation treatment, and finally the aniline group was added Lithium (0.8 mol% dosage) in tetrahydrofuran solution, react at room temperature for 75 minutes, the reaction solution is exposed to air to terminate the reaction, and the solvent is removed under reduced pressure to obtain the product borate, using mesitoxybenzene (83.84 mg, 0.5 mmol) as an internal standard , Dissolved with CDCl3, stirred for 10 minutes, sampled, and equipped with nuclear magnetic. The calculated 1H yield is 99%.
- the calculated 1H yield is 99%; if the n-butyllithium is changed to 2,4-bis(2,6-diisopropylanilino)-2-pentenyl lithium, the calculated 1H yield is 15%.
- NMR data of the product 1H NMR (400 MHz, CDCl3): ⁇ 3.88 (q, 2H, CH2), 1.25 (s, 36H, CH3), 1.21 (br s, 3H, CH3).
- the borate ester yield is 95%; when pinacol borane (363 ⁇ L, 2.5 mmol), the borate ester yield is 99%; the reaction time is 20 minutes The yield of boric acid ester is 99%; if n-butyllithium is replaced by triaryloxy rare earth catalyst Nd(OAr)3(THF)2, the product boric acid ester cannot be obtained.
- valeric acid 54.38 ⁇ L, 0.5 mmol
- pinacol borane 290 ⁇ L, 2 mmol
- n-butyl lithium 0.2 mol% amount
- valeric acid 54.38 ⁇ L, 0.5 mmol
- pinacol borane 290 ⁇ L, 2 mmol
- lithium anilide 0.6 mol% amount
- the calculated 1H yield is 99%; to the above system for removing the solvent after the hydroboration reaction, 110 g of silica gel and 300 mL of methanol were added, and the reaction was carried out at 50° C. for 115 minutes. After the reaction was completed, it was extracted three times with ethyl acetate, and the organic layers were combined with Dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and purify by silica gel (100-200 mesh) column chromatography using ethyl acetate/hexane (1:5 volume ratio) mixture as the eluent to obtain an aliphatic alcohol compound.
- the nuclear magnetic yield is 95%.
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Abstract
本发明涉及锂化合物的应用,具体涉及基于锂化合物制备硼酸酯的方法,包括以下步骤,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应得到硼酸酯;所述硼氢化反应的时间为10~80分钟,温度为室温,硼氢化反应结束后,接触空气中止反应,反应液减压除去溶剂,得到不同取代的硼酸酯;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。本发明公开的锂化合物可以在室温条件下高活性的催化羧酸和硼烷的硼氢化反应,锂化合物的用量为羧酸摩尔量的0.1%~0.9%,与已有的催化体系相比,利用了商业化试剂锂化合物,反应条件温和,在限定条件下不同取代基的硼酸酯的产率可达99%,并且可以进一步水解反应得到醇化合物。
Description
本发明涉及的商业化试剂锂化合物的应用,具体涉及基于锂化合物制备硼酸酯的方法。
有机硼酸酯可看作是正硼酸B(OH)
3中的氢被有机基团取代后的衍生物,此外还有偏硼酸酯(ROBO)
3。由于硼酸酯的稳定性和低毒性,被广泛应用于各个领域,它是合成含硼化合物的一种主要原料。硼酸酯类化合物不仅可以作为清洗剂中的防锈剂、防腐剂、聚合物添加剂、抗磨添加剂、汽车制动液、汽油添加剂、阻燃剂使用,而且可以用作润滑油添加剂等。
现有硼氢化方法都有明显的缺点:LiAlH
4和NaBH
4体系安全风险很大,SmI
2-H
2O-Et
3N体系需要过量很多的试剂,过渡金属配合物体系需要高温及高压下进行并且一方面要利用较难合成的催化剂,成本高;另一方面,催化反应需要60℃的反应温度以及24小时的反应时间。羧酸和醛酮亲核加成反应活性区别:(1)羧酸的活泼氢易离去,因此它的两个O实际上是等价的,所以从空间结构来看,羧基的位阻较大,并且羧基氢键的存在,使整个羰基的电子云密度较大,亲核试剂进攻活性中心比较难;(2)亲核试剂先进攻羰基碳,这个与碳上的电子云密度有关,密度小的先进攻,比如醛酮比酯、酰胺的电子云密度更小,所以活性高,会优先反应,空间效应大的不易反应;(3)形成过渡态的时候要看离去基团,醛酮的离去基团是烷基及氢,二者都不易离去,所以醛酮只发生加成,不发生消除,不同于羧酸及其衍生物。现有方法一方面要利用较难合成的催化剂,成本高;另一方面,催化反应需要60℃的反应温度以及24小时的反应时间。
本发明的发明目的是提供羧酸硼氢化反应制备硼酸酯的方法,即以锂化合物为高效催化剂催化羧酸与硼烷发生硼氢化反应,羧酸一般都是固体,羧酸与频哪醇硼烷的反应为非均相反应。
为达到上述发明目的,本发明采用的技术方案是:
基于锂化合物制备硼酸酯的方法,包括以下步骤,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应得到硼酸酯;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。
一种基于锂化合物制备醇化合物的方法,包括以下步骤,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应;硼氢化反应结束后加入硅胶、甲醇,进行水解反应,得到醇化合物;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。
锂化合物在催化羧酸与硼烷硼氢化反应中的应用;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。
本发明中,所述锂化合物为商业化的锂化合物试剂。
上述技术方案中,所述硼烷为频哪醇硼烷;所述羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸、己二酸、苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸、二苯基乙酸等。
上述技术方案中,所述羧酸和硼烷的用量摩尔比为 1:3~1:7。
上述技术方案中,所述硼氢化反应的温度为室温,时间为10~80分钟,锂化合物的用量为羧酸摩尔量的0.1%~0.9%。
优选的,锂化合物为正丁基锂,羧酸为苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸时,所述硼氢化反应的温度为室温,时间为40~50分钟,锂化合物的用量为羧酸摩尔量的0.4%~0.6%。优选的,锂化合物为苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,羧酸为苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸时,所述硼氢化反应的温度为室温,时间为70~80分钟,锂化合物的用量为羧酸摩尔量的0.7%~0.9%
优选的,锂化合物为正丁基锂,羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸或者己二酸时,所述硼氢化反应的温度为室温,时间为10~20分钟,正丁基锂的用量为羧酸摩尔量的0.1%~0.3%;优选的,锂化合物为苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸或者己二酸时,所述硼氢化反应的温度为室温,时间为50~60分钟,锂化合物的用量为羧酸摩尔量的0.5%~0.7%。
上述技术方案中,硼氢化反应结束后,接触空气中止反应,反应液减压除去溶剂,再加入硅胶、甲醇;水解反应结束后,反应液减压除去溶剂,然后经过柱层析得到醇化合物。
上述技术方案中,羧酸与硅胶、甲醇的用量比为1mmoL:2~2.2g:6mL;优选的,羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸或者己二酸时,羧酸与硅胶、甲醇的用量比为1mmoL:2.2g:6mL;羧酸为苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸时,羧酸与硅胶、甲醇的用量比为1mmoL:2g:6mL。
上述技术方案中,水解反应为50℃下反应115~120分钟;优选的,羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸或者己二酸时,水解反应为50℃下反应115分钟;羧酸为苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸时,水解反应为50℃下反应120分钟。
本发明公开的硼氢化反应的具体步骤为:
在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应;反应结束后,接触空气中止反应,反应液减压除去溶剂,得到不同取代的硼酸酯。可以在手套箱中实现惰性气体氛围,为常规技术。
室温下,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应,反应结束后,接触空气中止反应,减压除去溶剂后加入硅胶、甲醇,水解反应得到醇化合物。可以在手套箱中实现惰性气体氛围,为常规技术。
本发明中,所有原料经过无水无氧处理。
由于上述技术方案运用,本发明与现有技术相比具有下列优点:
1. 本发明首次发现商业化的锂化合物能高效的催化羧酸与硼烷发生硼氢化反应,高度符合原子经济合成。
2. 本发明公开的锂化合物催化羧酸与硼烷发生硼氢化反应的催化活性高(锂化合物的用量为羧酸摩尔量的0.1%~0.9%),反应条件温和(室温),反应时间短(10~50分钟),且反应产率高,反应简单可控,后处理简单。
3. 本发明公开的锂化合物催化羧酸的硼氢化对底物的适用范围宽,适用于不同取代基位置、不同电子效应的羧酸,为硼酸酯的工业化合成提供了更多选择;并且反应过程简单可控,收率高,产物后处理容易,适合工业化生产。
图1为实施例一反应示意图;
图2为对比例2,4-二(2,6-二异丙基苯胺基)-2-戊烯基锂的化学结构式。
下面结合实施例对本发明作进一步描述:
实施例一
反应示意图参见附图1,其他实施例反应过程与此类此。
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入苯甲酸 (61.1 mg, 0.5 mmol),用移液枪加入频哪醇硼烷(218 μL,
1.5 mmol),最后加入25μL正丁基锂的四氢呋喃溶液(0.1M) (0.5 mol%用量,下同),在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.15 mg,0.5
mmol)为内标,用CDCl
3溶解,搅拌10分钟,取样,配核磁。经计算
1H产率为97%,产物硼酸酯的核磁数据:
1H
NMR (400 MHz, CDCl
3) :δ 7.22– 7.32 (m, 5H, ArH),4.92
(s, 2H, CH
2), 1.26 (s, 36H, CH
3);频哪醇硼烷用量为2 mmol时,产物收率99%;频哪醇硼烷用量为361.2 μL, 2.5 mmol时,产物收率99%。如果将锂化合物换为三芳氧稀土催化剂Nd(OAr)
3(THF)
2,得不到产物。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物,核磁产率为93%。产物的核磁数据:
1H NMR (400 MHz, CDCl
3)
:δ 7.21– 7.29
(m, 5H, ArH), 4.62 (s, 2H, CH
2), 1.87 (br s, 1H, OH)。
对比例:2,4-二(2,6-二异丙基苯胺基)-2-戊烯基锂催化苯甲酸与频哪醇硼烷硼氢化反应
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入苯甲酸 (60.5 mg, 0.5 mmol),用移液枪加入频哪醇硼烷(238 μL,
1.65 mmol),最后加入25μL
2,4-二(2,6-二异丙基苯胺基)-2-戊烯基锂的四氢呋喃溶液 ( 0.1M ) (0.5 mol%用量),在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯(83.32
mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,核磁测定。经计算1H产率为12%。产物的核磁数据: 1H NMR (400
MHz, CDCl3) :δ 7.22– 7.32
(m, 5H, ArH),4.92 (s, 2H, CH2), 1.26 (s, 36H, CH3)。采用乙酸(28.6 μL, 0.5mmol)为原料,收率18%,产物的核磁数据: 1H NMR (400
MHz, CDCl3) :δ 3.87 (q, 2H, CH2), 1.24 (s, 36H, CH3),
1.20 (br s, 3H, CH3)。
2,4-二(2,6-二异丙基苯胺基)-2-戊烯基锂的化学结构式如图2。
实施例二
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入苯甲酸 (61.1 mg, 0.5 mmol),用移液枪加入频哪醇硼烷(218 μL,
1.5 mmol),最后加入40微升苯胺基锂的四氢呋喃溶液(0.1M)
(0.8 mol%用量,下同),在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.15 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%;如果将苯胺基锂换为三芳氧稀土催化剂Nd(OAr)3(THF)2,得不到产物。产物的核磁数据: 1H NMR (400 MHz, CDCl3) :δ 7.20– 7.30 (m, 5H,
ArH),4.91 (s, 2H, CH2), 1.24 (s, 36H, CH3)。
频哪醇硼烷用量为2 mmol时,产物收率99%;频哪醇硼烷用量为361.2 μL, 2.5 mmol时,产物收率99%。
在室温下反应80分钟,收率99%。
实施例三
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-氟苯甲酸
(70.8 mg,0.5 mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.99 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为91%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.20– 7.30
(m, 5H, ArH),4.91 (s, 2H, CH2), 1.24 (s, 36H, CH3)。
实施例四
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-溴苯甲酸 (100
mg,0.5 mmol),用移液枪加入频哪醇硼烷(289 μL,2 mmol),最后加入邻甲基苯胺基锂(0.8 mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(83.67 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为93%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.39 (br s, 2H, ArCH), 7.16 (t, 2H,
ArCH), 4.80 (s, 2H, OCH2), 1.19 (s, 36H, CH3)。
实施例五
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-氟苯甲酸
(70.8 mg,0.5 mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.99 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为90%。产物的核磁数据: 1H NMR (400 MHz, CDCl3):δ 7.21
(br s, 2H, ArCH), 6.91 (t, 2H, ArCH),4.75
(s, 2H, OCH2),1.15 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为89%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 7.22
(br s, 2H, ArCH), 6.98 (t, 2H, ArCH),4.56
(s, 2H, CH2), 2.27 (br s, 1H, OH)。
实施例六
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-溴苯甲酸 (100
mg,0.5 mmol),用移液枪加入频哪醇硼烷(289 μL,2 mmol),最后加入正丁基锂(0.5 mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.67 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为95%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.40 (br s, 2H, ArCH), 7.17 (t, 2H,
ArCH), 4.81 (s, 2H, OCH2), 1.20 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 7.42
(br s, 2H, ArCH), 7.19 (t, 2H, ArCH), 4.60 (s, 2H, CH2), 2.26 (br s, 1H, OH)。
实施例七
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-甲氧基苯甲酸
(76.2 mg,0.5 mmol),用移液枪加入频哪醇硼烷(290 μL,2 mmol),最后加正丁基锂(0.5 mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.23 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.41 (d, 1H, ArCH), 7.21 (t, 1H, ArCH),
6.95 (t, 1H, ArCH), 6.83 (d, 1H, ArCH), 4.97 (s,2H,OCH2), 1.26 (s,36H,CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 7.42
(d, 1H, ArCH), 7.23 (t, 1H, ArCH), 6.96 (t, 1H, ArCH), 6.84 (d, 1H, ArCH), 4.67
(s, 2H, CH2), 3.87 (br s, 1H, OH), 1.23 (s,3H,CH3)。
实施例八
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入1-萘甲酸
(85.4 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.42 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为91%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 8.01 (d, 1H, ArCH), 7.78-7.81 (m, 2H, ArCH), 7.74(d, 1H,
ArCH), 7.37-7.47 (m, 3H, ArCH), 5.36 (s, 2H, OCH2 ), 1.22 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为90%。产物的核磁数据:1H NMR (400 MHz, CDCl3):
δ 8.02 (d, 1H, ArCH), 7.80-7.82 (m, 2H,
ArCH), 7.73(d, 1H, ArCH), 7.38-7.48 (m, 3H, ArCH), 5.01 (s, 2H, CH2), 2.31 (br
s, 1H, OH)。
实施例九
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-叔丁基苯甲酸
(88.9 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.89 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 7.27 ( d, 2H, ArCH), 7.18 (d, 2H, ArCH) , 4.81 (s, 2H,
OCH2 ), 1.22 (s, 9H, CH3, tBu), 1.17 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为93%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ
7.28 ( d, 2H, ArCH), 7.16 (d, 2H, ArCH) , 4.51 (s, 2H, CH2), 2.12 (br s, 1H,
OH), 1.23 (s, 9H, CH3, tBu)。
实施例十
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-溴苯甲酸
(100.6 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.17 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 7.40 (d, 2H, ArCH), 7.18-7.21 (m, 1H, ArCH), 7.02 (t,
1H, ArCH), 4.89 (s, 2H, OCH2), 1.18 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3):δ 7.41
(d, 2H, ArCH), 7.19-7.22 (m, 1H, ArCH), 7.03 (t, 1H, ArCH),4.71 (s, 2H, CH2),
2.41 (br s, 1H, OH)。
实施例十一
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-碘苯甲酸
(124.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.09 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3):δ 7.56
(d, 2H, ArCH), 7.01 (d, 2H, ArCH), 4.77 (s, 2H, OCH2), 1.17 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3): δ 7.57 (d, 2H, ArCH), 7.02 (d, 2H, ArCH), 4.65 (s,
2H, CH2), 2.15 (br s, 1H, OH)。
实施例十二
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入3-苯丙酸
(74.9 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.89 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3):δ 7.17
(t, 2H, ,ArCH), 7.04- 7.09 (m, 3H, ArCH), 3.79 (t, 2H, CH2, OCH2), 2.61 (t, 2H,
CH2), 1.75-1.82 (m, 2H, CH2), 1.16 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为95%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 7.23
(t, 2H, ,ArCH), 7.11- 7.13 (m, 3H, ArCH), 3.62 (t, 2H, CH2, OCH2), 2.65 (t, 2H,
CH2), 1.78-1.85 (m, 2H, CH2), 1.61 (br s, 1H, OH)。
实施例十三
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入二苯基乙酸 (105.8 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.84 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 7.13-7.32 (m, 10H, ArCH), 4.41 (d, 2H, CH2, OCH2), 4.24
(t, 1H, CH), 1.23 (s,24H, CH3, pinBOBpin), 1.12 (s, 12H, CH3, OBpin)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ
7.20-7.31 (m, 10H, ArCH),4.19 (t, 1H, CH), 4.13 (d, 2H, CH2), 1.64-1.70 (t, 1H,
OH)。
实施例十四
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-甲基-5-溴-苯甲酸 (107.1 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.77 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 6.90 (d, 1H, ArCH), 7.19 (d, 1H, ArCH), 7.47 (s, 1H,
ArCH), 4.77 (s, 2H, OCH2), 2.12 (s, 3H, CH3), 1.17 (s, 36H, CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为95%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 6.91
(d, 1H, ArCH), 7.22 (d, 1H, ArCH), 7.57 (s, 1H, ArCH), 4.44 (s, 2H, OCH2), 2.15
(s, 3H, CH3),2.25 (br s, 1H, OH)。
实施例十五
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-苯基丁酸
(82.2 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.20 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 7.15-7.19 (m, 2H, ArCH), 7.08-7.10 (m, 3H, ArCH),
3.83-3.93 (m, 2H, CH2, OCH2), 2.57-2.66 (m, 1H, CH), 1.70-1.79 (m, 1H, CH2),
1.46-1.55 (m, 1H, CH2), 1.16 (s, 36H, CH3, OBpin & pinBOBpin), 0.74 (t, 3H,
CH3)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为93%。产物的核磁数据:1H NMR (400 MHz, CDCl3) : δ 7.17-7.30 (m, 5H, ArCH), 3.66-3.68 (m, 2H, CH2,OCH2),
2.64 (m, 1H, CH), 1.54-1.73 (m, 1H, CH2), 1.87(s,1H, OH), 0.82 (t, 3H, CH3)。
实施例十六
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入3-吲哚乙酸
(88.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(363 μL, 2.5 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.49 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为95%。产物的核磁数据: 1H NMR (400 MHz, CDCl3):δ 7.82
(d, 1H, ArCH), 7.45 (d, 1H, ArCH), 7.02-7.15 (m, 3H, ArCH), 4.06 (t, 2H, OCH2),
2.90 (t, 2H, CH2), 1.29 (s, 12H, CH3, N-Bpin ) 1.14 (s, 24H, CH3, pinBOBpin),
1.06 (s, 12H, CH3, OBpin)。
向硼氢化反应后除去溶剂的体系中加入1g硅胶、3mL甲醇,50℃下反应2h反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为91%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ
8.10 (s,1H,NH), 7.83 (d, 1H, ArCH), 7.45(d, 1H, ArCH), 7.03-7.15 (m, 3H, ArCH),
4.67 (t, 2H, OCH2), 3.28 (t, 2H, CH2), 1.90 (br s, 1H, OH)。
实施例十七
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入邻羧基苯乙酸 (90.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(508 μL, 3.5 mmol),最后加入正丁基锂(0.5
mol%用量)的四氢呋喃溶液,在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.02 mg,0.5
mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz, CDCl3):δ 7.33
(br s, 1H, ArCH), 7.11 (br s, 3H, ArCH), 4.90 (s, 2H, CH2)。 3.96 (t, 2H, CH2), 2.86 (t, 2H, CH2), 1.17 (s, 72H, CH3,
OBpin & pinBOBpin)。将硼酸酯进一步水解为醇,加入1g硅胶,以3mL甲醇为溶剂,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5)混合物作为洗脱剂,得到纯的伯醇,分离产率为93%。产物的核磁数据:1H NMR (400 MHz, CDCl3) :δ 7.32
(br s, 1H, ArCH), 7.12 (br s, 3H, ArCH), 4.53 (s, 2 H, CH2), 3.76 (t, 2 H,
CH2OH), 3.7 (br, 1 H, OH), 3.1 (br s, 1 H, OH), 2.86 (t, 2 H, CH2)。
实施例十八
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-甲氧基苯甲酸
(76.2 mg,0.5 mmol),用移液枪加入频哪醇硼烷(290 μL,2 mmol),最后加入苯胺基锂(0.8 mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.23 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.40 (d, 1H, ArCH), 7.21 (t, 1H, ArCH),
6.94 (t, 1H, ArCH), 6.82 (d, 1H, ArCH), 4.96 (s,2H,OCH2), 1.25 (s,36H,CH3)。
实施例十九
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入1-萘甲酸
(85.4 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.42 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为93%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 8.01 (d, 1H,
ArCH), 7.78-7.80 (m, 2H, ArCH), 7.73(d, 1H, ArCH), 7.36-7.46 (m, 3H, ArCH),
5.35 (s, 2H, OCH2 ), 1.21 (s, 36H, CH3)。
实施例二十
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-叔丁基苯甲酸
(88.9 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入2-甲氧基苯胺基锂(0.8 mol%用量)的四氢呋喃溶液,在室温下反应80分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(83.89 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.25 ( d, 2H, ArCH), 7.16 (d, 2H, ArCH)
, 4.79 (s, 2H, OCH2 ), 1.20 (s, 9H, CH3, tBu), 1.15 (s, 36H, CH3)。
实施例二十一
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-溴苯甲酸
(100.6 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.17 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 7.39 (d, 2H,
ArCH), 7.17-7.20 (m, 1H, ArCH), 7.01 (t, 1H, ArCH), 4.88 (s, 2H, OCH2), 1.17
(s, 36H, CH3)。
实施例二十二
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入4-碘苯甲酸
(124.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入4-甲氧基苯胺基锂(0.8 mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.09 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.55 (d, 2H, ArCH), 7.01 (d, 2H,
ArCH), 4.76 (s, 2H, OCH2), 1.16 (s, 36H, CH3)。
实施例二十三
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入3-苯丙酸
(74.9 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.89 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.16 (t, 2H, ,ArCH), 7.03- 7.08 (m, 3H,
ArCH), 3.78 (t, 2H, CH2, OCH2), 2.60 (t, 2H, CH2), 1.74-1.81 (m, 2H, CH2), 1.15
(s, 36H, CH3)。
实施例二十四
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入二苯基乙酸 (105.8 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.84 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 7.12-7.31 (m,
10H, ArCH), 4.40 (d, 2H, CH2, OCH2), 4.23 (t, 1H, CH), 1.22 (s,24H, CH3,
pinBOBpin), 1.11 (s, 12H, CH3, OBpin)。
实施例二十五
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-甲基-5-溴-苯甲酸 (107.1 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.77 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400 MHz,
CDCl3):δ 6.91 (d, 1H, ArCH), 7.20 (d, 1H, ArCH),
7.48 (s, 1H, ArCH), 4.78 (s, 2H, OCH2), 2.13 (s, 3H, CH3), 1.18 (s, 36H, CH3)。
实施例二十六
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-苯基丁酸
(82.2 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.8mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.20 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 7.14-7.18 (m,
2H, ArCH), 7.07-7.10 (m, 3H, ArCH), 3.82-3.92 (m, 2H, CH2, OCH2), 2.56-2.65 (m,
1H, CH), 1.70-1.80 (m, 1H, CH2), 1.45-1.54 (m, 1H, CH2), 1.15 (s, 36H, CH3,
OBpin & pinBOBpin), 0.73 (t, 3H, CH3)。
实施例二十七
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入3-吲哚乙酸
(88.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(363 μL, 2.5 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.49 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为96%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.81 (d, 1H, ArCH), 7.44(d, 1H, ArCH),
7.01-7.13 (m, 3H, ArCH), 4.05 (t, 2H, OCH2), 2.89 (t, 2H, CH2), 1.28 (s, 12H,
CH3, N-Bpin ) 1.13 (s, 24H, CH3, pinBOBpin), 1.05 (s, 12H, CH3, OBpin)。
实施例二十八
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入邻羧基苯乙酸 (90.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(508 μL, 3.5 mmol),最后加入苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.02 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.32 (br s, 1H, ArCH), 7.10 (br s, 3H,
ArCH), 4.89 (s, 2H, CH2),3.95 (t, 2H,
CH2), 2.85 (t, 2H, CH2), 1.16 (s, 72H, CH3, OBpin & pinBOBpin)。
实施例二十九
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入苯甲酸 (61.1 mg, 0.5 mmol),用移液枪加入频哪醇硼烷(218 μL,
1.5 mmol),最后加入40微升对甲基苯胺基锂的四氢呋喃溶液(0.1M)
(0.8mol%用量),在室温下反应70分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.15 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3) :δ 7.23–
7.33(m, 5H, ArH),4.93 (s, 2H,
CH2), 1.27 (s, 36H, CH3)。
实施例三十
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入3-吲哚乙酸
(88.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(363 μL, 2.5 mmol),最后加入2,6-二甲基苯胺基锂(0.8mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.49 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为96%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.86 (d, 1H, ArCH), 7.49 (d, 1H, ArCH),
7.06-7.18 (m, 3H, ArCH), 4.10 (t, 2H, OCH2), 2.94 (t, 2H, CH2), 1.33 (s, 12H,
CH3, N-Bpin ) 1.18 (s, 24H, CH3, pinBOBpin), 1.10 (s, 12H, CH3, OBpin)。
实施例三十一
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-苯基丁酸
(82.2 mg,0.5 mmol,用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入2,6-二异丙基苯胺基锂(0.8mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.20 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 7.20-7.24 (m,
2H, ArCH), 7.13-7.15 (m, 3H, ArCH), 3.88-3.98 (m, 2H, CH2, OCH2), 2.62-2.71 (m,
1H, CH), 1.75-1.84 (m, 1H, CH2), 1.51-1.60 (m, 1H, CH2), 1.21 (s, 36H, CH3,
OBpin & pinBOBpin), 0.79 (t, 3H, CH3)。
实施例三十二
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入2-甲基-5-溴-苯甲酸 (107.1 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入对甲基苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (83.77 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 6.92 (d, 1H,
ArCH), 7.21 (d, 1H, ArCH), 7.49 (s, 1H, ArCH), 4.79 (s, 2H, OCH2), 2.14 (s, 3H,
CH3), 1.19 (s, 36H, CH3)。
实施例三十三
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入邻羧基苯乙酸 (90.0 mg,0.5 mmol,用移液枪加入频哪醇硼烷(508 μL, 3.5 mmol),最后加入邻甲基苯胺基锂(0.8
mol%用量)的四氢呋喃溶液,在室温下反应80分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.02 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 7.36 (br s, 1H, ArCH), 7.14 (br s, 3H,
ArCH), 4.93 (s, 2H, CH2),3.99 (t, 2H,
CH2), 2.89 (t, 2H, CH2), 1.20 (s, 72H, CH3, OBpin & pinBOBpin)。
实施例三十四
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入1-萘甲酸
(85.4 mg,0.5 mmol,用移液枪加入频哪醇硼烷(289 μL, 2 mmol),最后加入2,6-二甲基苯胺基锂(0.7mol%用量)的四氢呋喃溶液,在室温下反应75分钟,将反应液接触空气终止反应,减压除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(83.42 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为93%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 8.05 (d, 1H,
ArCH), 7.83-7.85 (m, 2H, ArCH), 7.78 (d, 1H, ArCH), 7.38-7.48 (m, 3H, ArCH),
5.37 (s, 2H, OCH2 ), 1.26 (s, 36H, CH3)。
实施例三十五
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入乙酸(28.6 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入10 μL正丁基锂的四氢呋喃溶液(0.1M) (0.2 mol%用量,下同),在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.08 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%;如果将正丁基锂换为2,4-二(2,6-二异丙基苯胺基)-2-戊烯基锂经计算1H产率为15%。产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 3.88 (q, 2H, CH2), 1.25 (s, 36H, CH3), 1.21 (br s, 3H,
CH3)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到脂肪族醇化合物。核磁产率为95%。产物的核磁数据:1H NMR (400 MHz, CDCl3):δ 3.69
(q, 2H, CH2), 2.92 (br s, 1H,OH), 1.22 (br s, 3H, CH3)。
当频哪醇硼烷(218 μL, 1.5 mmol)时,硼酸酯收率95%;频哪醇硼烷(363 μL, 2.5 mmol)时,硼酸酯收率99%;反应时间为20分钟,硼酸酯收率99%;如果将正丁基锂换为三芳氧稀土催化剂Nd(OAr)3(THF)2,得不到产物硼酸酯。
实施例三十六
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入戊酸(54.38 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.2
mol%用量)的四氢呋喃溶液,在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.12 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为92%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.81 (t, 2H,
OCH2), 1.52-1.56 (m, 2H,CH2), 1.30-1.52 (m, 4H, CH2), 1.28(s, 36H, CH),0.86
(t, 3H, CH3)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为92%。产物的核磁数据:1H NMR (400 MHz, CDCl3):δ 3.63
(t, 2H, OCH2), 1.59 (m, 2H,CH2), 1.35 (m,2H, CH2), 2.35(br s, 1H, OH),0.90
(t, 3H, CH3)。
实施例三十七
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入己酸(62.52 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.2
mol%用量)的四氢呋喃溶液,在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.01 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为90%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.76 (t, 2H,
OCH2), 1.46-1.52 (m, 2H,CH2), 1.24-1.35 (m, 6H, CH2), 1.19(s, 48H, CH3),0.82
(t, 3H, CH3)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为89%。产物的核磁数据:1H NMR (400 MHz, CDCl3): δ 3.75 (t, 2H, OCH2), 1.47-1.52 (m, 2H,CH2), 1.26-1.36 (m,
6H, CH2), 1.71(br s, 1H, OH3),0.82 (t, 3H, CH3)。
实施例三十八
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入庚酸(70.90 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入正丁基锂(0.2
mol%用量)的四氢呋喃溶液,在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.05 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为90%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.71 (t, 2H,
OCH2), 1.41-1.47 (m, 2H,CH2), 1.19-1.30 (m, 8H, CH2), 1.24(s, 48H, CH3),0.77
(t, 3H, CH3)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为88%。产物的核磁数据:1H NMR (400 MHz, CDCl3): δ 3.72 (t, 2H, OCH2), 1.42-1.47 (m, 2H,CH2), 1.20-1.30 (m,
8H, CH2), 1.76(br s, 1H, OH3),0.77 (t, 3H, CH3)。
实施例三十九
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入三甲基乙酸(50.7 mg, 0.5mmol),用移液枪加入频哪醇硼烷(288 μL, 2
mmol),最后加入正丁基锂(0.2 mol%用量)的四氢呋喃溶液,在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.08 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3) δ 3.43 (s, 2H,
OCH2), 1.17 (s, 36H, CH3, OBpin & pinBOBpin), 0.82 (s, 9H, CH3)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为92%。产物的核磁数据:1H NMR (400 MHz, CDCl3): δ 3.20(s, 2H, OCH2), 1.97 (br s, 1H, OH), 0.81 (s, 9H,
CH3)。
实施例四十
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入己二酸(72.9 mg, 0.5mmol),用移液枪加入频哪醇硼烷(508 μL,
3.5 mmol),最后加入正丁基锂(0.2 mol%用量)的四氢呋喃溶液,在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(83.90 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 3.77 (t, 4H, OCH2), 1.48-1.50 (m, 4H,
CH2), 1.28-1.30 (m, 4H, CH2), 1.17 (s, 72H, CH3, OBpin & pinBOBpin)。
向上述硼氢化反应后除去溶剂的体系中加入1.1g硅胶、3mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物。核磁产率为92%。产物的核磁数据:1H NMR (400 MHz, CDCl3): δ 3.76 (t, 4H, OCH2), 1.48-1.50 (m, 4H, CH2), 1.29-1.31
(m, 4H, CH2), 2.25 (br s,2H, OH)。
实施例四十一
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入乙酸(28.6 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入30 μL苯胺基锂的四氢呋喃溶液(0.1M) (0.6 mol%用量,下同),在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.08 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.86 (q, 2H,
CH2), 1.24 (s, 36H, CH3), 1.20 (br s, 3H, CH3)。
当频哪醇硼烷(218 μL, 1.5 mmol)时,收率96%;频哪醇硼烷(363 μL, 2.5 mmol)时,收率99%;反应时间为30分钟,收率99%;如果将苯胺基锂换为三芳氧稀土催化剂Nd(OAr)3(THF)2,得不到产物;将苯胺基锂换为对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,经计算产物1H产率都为99%。
实施例四十二
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入戊酸(54.38 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.6
mol%用量)的四氢呋喃溶液,在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.12 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为92%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.80(t, 2H,
OCH2), 1.51-1.55 (m, 2H,CH2), 1.29-1.51 (m, 4H, CH2), 1.27(s, 36H, CH),0.85
(t, 3H, CH3)。
实施例四十三
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入己酸(62.52 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.6
mol%用量)的四氢呋喃溶液,在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.01 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为90%。
将苯胺基锂换为对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,经计算产物1H产率分别为91%、90%、93%、90%、91%、92%。
产物的核磁数据: 1H NMR (400 MHz, CDCl3): δ 3.75 (t, 2H, OCH2), 1.45-1.51 (m, 2H,CH2), 1.23-1.34 (m,
6H, CH2), 1.18(s, 48H, CH3),0.81 (t, 3H, CH3)。
实施例四十四
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入庚酸(70.90 μL,
0.5mmol),用移液枪加入频哪醇硼烷(290 μL, 2 mmol),最后加入苯胺基锂(0.6
mol%用量)的四氢呋喃溶液,在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.05 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为90%。产物的核磁数据: 1H NMR (400
MHz, CDCl3): δ 3.70 (t, 2H,
OCH2), 1.40-1.46 (m, 2H,CH2), 1.18-1.29 (m, 8H, CH2), 1.23(s, 48H, CH3),0.76
(t, 3H, CH3)。
实施例四十五
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入三甲基乙酸(50.7 mg, 0.5mmol),用移液枪加入频哪醇硼烷(289 μL, 2
mmol),最后加入苯胺基锂(0.6 mol%用量)的四氢呋喃溶液,在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(84.08 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。将苯胺基锂换为对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,经计算产物1H产率分别为96%、99%、98%、99%、99%、97%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 3.42(s, 2H, OCH2), 1.16 (s, 36H, CH3,
OBpin & pinBOBpin), 0.81 (s, 9H, CH3)。
实施例四十六
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入己二酸(72.9 mg, 0.5mmol),用移液枪加入频哪醇硼烷(508微升, 3.5 mmol),最后加入苯胺基锂(0.6 mol%用量)的四氢呋喃溶液,在室温下反应55分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯
(83.90 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%。产物的核磁数据: 1H NMR (400
MHz, CDCl3):δ 3.76 (t, 4H, OCH2), 1.47-1.49 (m, 4H,
CH2), 1.27-1.29 (m, 4H, CH2), 1.16 (s, 72H, CH3, OBpin & pinBOBpin)。将苯胺基锂换为对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂,经计算产物1H产率分别为99%、99%、98%、99%、97%、96%。
实施例四十七
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入苯甲酸 (50mmol),用移液枪加入频哪醇硼烷(200 mmol),最后加入正丁基锂的四氢呋喃溶液(0.1M)
(0.5 mol%用量),在室温下反应45分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯(84.15
mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁,经计算1H产率为99%;向硼氢化反应后除去溶剂的体系中加入100g硅胶、300mL甲醇,50℃下反应2h,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到醇化合物,核磁产率为94%。
实施例四十八
在惰性气体氛围下,向经过脱水脱氧处理后的反应瓶中加入乙酸(50mmol),用移液枪加入频哪醇硼烷(200
mmol),最后加入正丁基锂的四氢呋喃溶液(0.1M) (0.2 mol%用量),在室温下反应15分钟,将反应液接触空气,除去溶剂,得到产物硼酸酯,以均三甲氧基苯 (84.08 mg,0.5 mmol)为内标,用CDCl3溶解,搅拌10分钟,取样,配核磁。经计算1H产率为99%; 向上述硼氢化反应后除去溶剂的体系中加入110g硅胶、300mL甲醇,50℃下反应115分钟,反应结束后,用乙酸乙酯萃取三次,合并有机层,用无水硫酸钠干燥,减压除去溶剂,通过硅胶(100-200目)柱色谱法纯化,用乙酸乙酯/己烷(1:5体积比)混合物作为洗脱剂,得到脂肪族醇化合物,核磁产率为95%。
Claims (10)
- 基于锂化合物制备硼酸酯的方法,包括以下步骤,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应得到硼酸酯;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。
- 根据权利要求1所述基于锂化合物制备硼酸酯的方法,其特征在于,所述硼烷为频哪醇硼烷;所述羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸、己二酸、苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸。
- 根据权利要求1所述基于锂化合物制备硼酸酯的方法,其特征在于,所述羧酸和硼烷的用量摩尔比为 1:3~1:7;所述锂化合物的用量为羧酸摩尔量的0.1%~0.9%。
- 根据权利要求1所述基于锂化合物制备硼酸酯的方法,其特征在于,所述硼氢化反应的温度为室温;所述硼氢化反应的时间为10~80分钟。
- 根据权利要求1所述基于锂化合物制备硼酸酯的方法,其特征在于,硼氢化反应结束后,接触空气中止反应,反应液减压除去溶剂,得到硼酸酯。
- 一种基于锂化合物制备醇化合物的方法,包括以下步骤,在惰性气体氛围下,将硼烷和羧酸混合,再加入催化剂锂化合物,然后进行硼氢化反应;硼氢化反应结束后加入硅胶、甲醇,进行水解反应,得到醇化合物;所述锂化合物为正丁基锂、苯胺基锂、对甲基苯胺基锂、邻甲基苯胺基锂、2-甲氧基苯胺基锂、4-甲氧基苯胺基锂、2,6,-二甲基苯胺基锂或者2,6-二异丙基苯胺基锂。
- 根据权利要求6所述基于锂化合物制备醇化合物的方法,其特征在于,硼氢化反应结束后,接触空气中止反应,反应液减压除去溶剂,再加入硅胶、甲醇;水解反应结束后,反应液减压除去溶剂,然后经过柱层析得到醇化合物。
- 根据权利要求6所述基于锂化合物制备醇化合物的方法,其特征在于,羧酸与硅胶、甲醇的用量比为1mmoL:2~2.2g:6mL;羧酸和硼烷的用量摩尔比为 1:3~1:7;所述锂化合物的用量为羧酸摩尔量的0.1%~0.9%。
- 根据权利要求6所述基于锂化合物制备醇化合物的方法,其特征在于,水解反应为50℃下反应115~120分钟;所述硼氢化反应的温度为室温;所述硼氢化反应的时间为10~80分钟。
- 根据权利要求6所述基于锂化合物制备醇化合物的方法,其特征在于,所述硼烷为频哪醇硼烷;所述羧酸为乙酸、己酸、戊酸、庚酸、三甲基乙酸、己二酸、苯甲酸、4-溴苯甲酸、4-氟苯甲酸、1-萘甲酸、2-甲氧基苯甲酸、邻羧基苯乙酸、3-吲哚乙酸、2-苯基丁酸、2-甲基-5-溴-苯甲酸、4-叔丁基苯甲酸、2-溴苯甲酸、4-碘苯甲酸、3-苯丙酸或者二苯基乙酸。
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Non-Patent Citations (2)
Title |
---|
SESHA KISAN ET AL.: "Ruthenium-catalyzed Deoxygenative Hydroboration of Carboxylic Acids", ACS CATALYSIS, vol. 8, 26 April 2018 (2018-04-26), pages 4772 - 4776, XP055712325, DOI: 10.1021/acscatal.8b00900 * |
XING, QIYI ET AL.: "Basic Organic Chemistry", 30 June 2005, HIGHER EDUCATION PRESS, CN, ISBN: 7-04-016637-2, article XING, QIYI ET AL.: "Reduction of Carboxylic Acid", pages: 582 - 583, XP009521536 * |
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