CN101781197B - Preparation method of chiral binaphthyl dicarboxylic acid - Google Patents
Preparation method of chiral binaphthyl dicarboxylic acid Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- PNKBWDYDQQBDSN-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalene-2,3-dicarboxylic acid Chemical compound C1=CC=C2C(C=3C4=CC=CC=C4C=C(C=3C(O)=O)C(=O)O)=CC=CC2=C1 PNKBWDYDQQBDSN-UHFFFAOYSA-N 0.000 title claims abstract description 15
- 230000003287 optical effect Effects 0.000 claims abstract description 6
- 238000001953 recrystallisation Methods 0.000 claims abstract description 5
- 230000004224 protection Effects 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 230000006837 decompression Effects 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- 238000001556 precipitation Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000000967 suction filtration Methods 0.000 claims description 4
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 238000005286 illumination Methods 0.000 claims description 3
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 3
- 235000011056 potassium acetate Nutrition 0.000 claims description 3
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims description 3
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 claims description 3
- 229960002218 sodium chlorite Drugs 0.000 claims description 3
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 238000010790 dilution Methods 0.000 claims description 2
- 239000012895 dilution Substances 0.000 claims description 2
- 239000010410 layer Substances 0.000 claims description 2
- 229910052759 nickel Inorganic materials 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 9
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract description 4
- 238000000926 separation method Methods 0.000 abstract description 4
- PPTXVXKCQZKFBN-UHFFFAOYSA-N (S)-(-)-1,1'-Bi-2-naphthol Chemical compound C1=CC=C2C(C3=C4C=CC=CC4=CC=C3O)=C(O)C=CC2=C1 PPTXVXKCQZKFBN-UHFFFAOYSA-N 0.000 abstract description 3
- 230000003647 oxidation Effects 0.000 abstract description 3
- 238000007254 oxidation reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 2
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 2
- 238000007069 methylation reaction Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 230000031709 bromination Effects 0.000 abstract 1
- 238000005893 bromination reaction Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 230000011987 methylation Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000001590 oxidative effect Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 4
- ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- -1 2-naphthalene halide Chemical class 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- IYHBWFYMPICERQ-UHFFFAOYSA-N CC1=C(C(O)=O)C(Br)=CC(Br)=C1C(O)=O Chemical compound CC1=C(C(O)=O)C(Br)=CC(Br)=C1C(O)=O IYHBWFYMPICERQ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Substances OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of chiral binaphthyl dicarboxylic acid. The preparation method of the invention starts from chiral binaphthol which is finally oxidized into the chiral binaphthyl dicarboxylic acid through Tf2O protection, methylation, bromination, esterification, hydrolysis to alcohol and oxidation to aldehyde. The method concretely comprises the following steps as shown inspecification. In the process of preparing the chiral binaphthyl dicarboxylic acid, all intermediate compounds and final products can be purified through recrystallization, the chromatogram preparation separation and purification is not needed, and the optical purity of products is higher than 99 percent. The method of the invention has the advantages that the operation is simple, convenient and safe, raw materials are low-priced and can be obtained easily, the total yield reaches 74.8 percent, and the invention is suitable for industrial production.
Description
Technical field
The present invention relates to the preparation field of binaphthyl dicarboxylic acid, be specifically related to a kind of preparation method of chiral binaphthyl dicarboxylic acid.
Background technology
Optically pure binaphthyl dicarboxylic acid and derivative thereof are important catalyst and the synthetic intermediates of asymmetric catalysis.At present domestic price all 1000 yuans/more than the gram, and and non-commercial can get, its study on the synthesis has certain application prospect and commercial value.
The preparation method who has reported on the document mainly contains at present:
1) chiral base resolution of racemic binaphthyl dicarboxylic acid or its precursor are (as Japanese Patent JP 02076838; Japanese Patent JP 01186840; WO 9946257; Bull.Chem.Soc.Jpn.1989,62,956; Bull.Chem.Soc.Jpn.1988,61,1032; Chem.Commun.2006,1070; Synthesis, 2000,1677).
2) racemize 2,2 under the enzyme catalysis '-dihydroxymethyl-1,1 '-kinetic resolution (Tetrahedron:Asymmetry of dinaphthalene, 1999,10,4763-4768), perhaps the acid of racemize dinaphthalene and chirality assistant agent are formed ester and carry out kinetic resolution (J.Org.Chem.1995,60,4968).
3) the intermolecular or intramolecularly Ullmann linked reaction by achirality 2-naphthalene halide derivative gets the acid of racemize dinaphthalene, carry out again chiral separation (as Organometallics, 1991,10,3438-3448; Tetrahedron:Asymmetry, 1996,7,2971; Tetrahedron:Asymmetry, 1997,8,2709), perhaps directly prepare (as Qin Chuan etc., organic chemistry, 2002,22,1013 by the intermolecular of chirality 2-naphthalene halide derivative or intramolecularly cis-selectivity Ullmann linked reaction; Bull.Chem.Soc.Jpn, 1981,54,3522).
4) from the acid of chiral binaphthyl raw material preparation dinaphthalene, as: chirality 2,2 '-two bromo-1,1 '-dinaphthalene and CO
2Carbonylation reaction (Tetrahedron Lett.2004,45,3485); Chirality 2,2 '-two trifluoromethanesulfonic acid bases-1,1 '-the direct methoxycarbonyl reaction of dinaphthalene and CO obtains chiral binaphthyl acid esters (Tetrahedron Lett.1993,34,1615); Chirality 2,2 '-two iodo-1,1 '-dinaphthalene or chirality 2,2 '-two trifluoromethanesulfonic acid bases-1,1 '-the cyano group reaction of dinaphthalene, again cyano group is changed into acid (Collection of Czechoslovak Chemical Communications, 2000,65,729).
Can realize that at present industrialized method mainly is by chiral separation, weak point is that the resolving agent consumption is big, and cost is higher, and some resolving agent is also toxic.From the acid of chiral binaphthyl raw material preparation dinaphthalene, route is succinct, but reaction conditions control is strict, also uses highly toxic CO gas sometimes, and the suitability for industrialized production difficulty is big.
Summary of the invention
The objective of the invention is to shortcomings such as the resolving agent consumption that exists in the technology according to the existing preparation chiral binaphthyl dicarboxylic acid is big, cost is high, resolving agent is toxic, the production difficulty is big, provide a kind of easy to prepare easy, reduced the preparation method of the chiral binaphthyl dicarboxylic acid of production cost.
The object of the invention is achieved by the following technical programs:
The inventive method is from chiral binaphthol, through process Tf
2O protects, methylates, be hydrolyzed into alcohol behind the bromo, one-tenth ester group, is oxidized to aldehyde, finally is oxidized to chiral binaphthyl dicarboxylic acid, specifically comprises the steps:
Particularly, preparation method of the present invention comprises the steps:
(a) the trifluoromethane sulfonic acid reaction of hydroxyl: chiral binaphthol is dissolved in the methylene dichloride, drips trifluoromethyl sulfonic acid anhydride under the low temperature, the consumption of acid anhydrides is 1.5～3 equivalents of dinaphthol, stirring at room 2～10h, and reaction solution gets intermediate II through aftertreatment;
(b) methylation reaction: with the NiCl of intermediate II and 1～5wt%
2(dppp) be dissolved in ether, drip the MeMgI of 3～6 equivalents under the low temperature, stirred overnight at room temperature, reaction solution gets intermediate III through aftertreatment;
(c) bromo-reaction: the N-bromo lake imide of intermediate III and 2～4 equivalents and the Diisopropyl azodicarboxylate of 10～20wt% are dissolved in hexanaphthene, and night is flow through in illumination next time, and reaction solution gets intermediate compound IV through aftertreatment;
(d) ester group reaction: potassium acetate, the Tetrabutyl amonium bromide of intermediate compound IV and 3～5 equivalents are dissolved in N, dinethylformamide, backflow is spent the night, and reaction solution gets intermediate V through aftertreatment;
(e) hydrolysis reaction: intermediate V is mixed with the KOH aqueous solution and the tetrahydrofuran (THF) of 50wt%, backflow 24h, reaction solution gets intermediate VI through aftertreatment;
(f) be oxidized to aldehyde: intermediate VI is mixed with the Manganse Dioxide of 5～10 equivalents, add oxidation solvent, reaction solution gets intermediate VII through aftertreatment;
(g) be oxidized to acid: with intermediate VII and NaH
2PO
42H
2O and H
2O
2Be dissolved in tetrahydrofuran (THF), drip the sodium chlorite aqueous solution, stirring at normal temperature 1～3h, the S-WAT neutralization reaction, be spin-dried for, with hcl acidifying, extraction, activated carbon filtration, drying, be spin-dried for, recrystallization, obtain pure product VIII, i.e. chiral binaphthyl dicarboxylic acid.
As a kind of preferred version, in the step among the preparation method of the present invention (f), described oxidizing reaction temperature is room temperature to 80 ℃, and the reaction times is 2～24h; Described oxidation solvent is N, dinethylformamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), toluene, dioxane, acetone, methylene dichloride or ethylene dichloride; Described oxidizing reaction is carried out under the strong oxidizer condition, and strong oxidizer is Na
2Cr
2O
7, KMnO
4, K
2Cr
2O
7, PbO
2, K
2Cr
2O
4, MnO
2Or CrO
3
As a kind of preferred version, in the step among the preparation method of the present invention (g), described oxidizing reaction temperature is room temperature to 100 ℃, and the reaction times is 1～24h; The solvent of described oxidizing reaction is N, dinethylformamide, dimethyl sulfoxide (DMSO), tetrahydrofuran (THF), toluene, dioxane, acetone, methylene dichloride or ethylene dichloride; Described oxidizing reaction is carried out under the strong oxidizer condition, and strong oxidizer is Na
2Cr
2O
7, KMnO
4, K
2Cr
2O
7, PbO
2, K
2Cr
2O
4, CrO
3, HClO, HClO
3, HClO
4Or H
2O
2
Compared with prior art, the present invention has following beneficial effect:
Among the preparation method of the present invention, used raw material---chiral binaphthol is cheap and easy to get, has reduced cost; The easy control of reaction conditions of the inventive method, easy and simple to handle, all intermediates and the finished product in the preparation process all can be purified by recrystallization, need not the preparative chromatography separation and purification, the optical purity of product reaches 74.8% greater than 99% total recovery, always is suitable for scale operation.
Embodiment
Further explain the present invention below in conjunction with embodiment, but embodiment does not do any type of restriction to the present invention.
Embodiment 1
(R)-2,2 '-two trifluoromethanesulfonic acid bases-1,1 '-dinaphthalene (II)
Under the nitrogen protection, with (R)-dinaphthol (11.46g, 40mmol) and triethylamine (17mL 120mmol) is dissolved in methylene dichloride, slowly splash under-78 ℃ trifluoromethyl sulfonic acid anhydride (18mL, 107mmol), stirring at room 2h.Reaction solution is poured 50mL dilute hydrochloric acid into, tell organic layer after, the water layer dichloromethane extraction merges organic layer, uses saturated sodium bicarbonate and saturated common salt water washing respectively, anhydrous sodium sulfate drying.The evaporated under reduced pressure solvent gets and slightly produces II22.2g, and productive rate is greater than 99%.
(R)-2,2 '-dimethyl-1,1 '-dinaphthalene (III)
II is slightly produced 22.0g and NiCl
2(dppp) (0.634g 1.2mmol) is dissolved in ether, slowly splashes into MeMgBr (160mmol, 3M in Et under-10 ℃
2O), stirred overnight at room temperature.Reaction solution is removed nickel catalyzator with ether dilution after-filtration, and filtrate is respectively with 0.5M dilute hydrochloric acid and saturated common salt washing, anhydrous sodium sulfate drying.The evaporated under reduced pressure solvent gets and slightly produces III 11.3g, and productive rate is greater than 99%.
1H?NMR(400MHz，CDCl
3)：
(d，2H，J＝8.4Hz，Ar-H)，7.88(d，2H，J＝8.4Hz，Ar-H)，7.51(d，2H，J＝8.4Hz，Ar-H)，7.39(ddd，2H，J＝8.4，6.9，1.2Hz，Ar-H)，7.20(ddd，2H，J＝8.4，6.9，1.2Hz，Ar-H)，7.04(d，2H，J＝8.4Hz，Ar-H)，1.96(s，6H，Ar-CH3)。
(R)-2,2 '-the dibromo methyl isophthalic acid, 1 '-dinaphthalene (IV)
With III slightly produce 11.26g, N-bromosuccinimide (18.6g, 104mmol) and Diisopropyl azodicarboxylate (0.81g 5mmol) is dissolved in hexanaphthene, and night is flow through in illumination next time.Cooling adds 40mL ethyl acetate and 40mL water in the reaction solution, stir 1h.Suction filtration is removed pale precipitation.Filtrate is used ethyl acetate extraction, merges the organic layer anhydrous sodium sulfate drying.The evaporated under reduced pressure solvent gets and slightly produces IV 16.5g, productive rate 94%.
1H?NMR(400MHz，CDCl
3)：
(d，2H，J＝8.6Hz，Ar-H)，7.85(d，2H，J＝8.2Hz，Ar-H)，7.67(d，2H，J＝8.8Hz，Ar-H)，7.39(m，2H，Ar-H)，7.20(m，2H，Ar-H)，7.00(d，2H，J＝8.5Hz，Ar-H)，4.17(s，4H，CH
2)。
(R)-2,2 '-oxalic acid methoxycarbonyl-1,1 '-dinaphthalene (V)
350mL N, add successively in the dinethylformamide IV slightly produce 16.5g, potassium acetate (19.6g, 0.20mol) and Tetrabutyl amonium bromide (6.44g, 0.20mol), stirring and refluxing is spent the night.Cooling adds the 500mL ether in the reaction solution, suction filtration is removed white precipitate, and filtrate decompression removes solvent, gets slightly to produce V 15.0g, and productive rate is greater than 99%.
(R)-2,2 '-dihydroxymethyl-1,1 '-dinaphthalene (VI)
The KOH aqueous solution that V is slightly produced 15.0g and 170mL 50% adds in the 170mL tetrahydrofuran (THF), stirring and refluxing reaction 24h.Cooling, the reaction solution ether extraction merges the organic phase anhydrous sodium sulfate drying.Decompression removes solvent, gets and slightly produces VI 10.2g, productive rate 86%.
1H?NMR(400MHz，CDCl
3)：7.97(d，2H，J＝8.6Hz，Ar-H)，7.91(d，2H，J＝8.2Hz，Ar-H)，7.70(d，2H，J＝8.8Hz，Ar-H)，7.45(m，2H，Ar-H)，7.23(m，2H，Ar-H)，7.02(d，2H，J＝8.5Hz，Ar-H)，4.38(d，J＝11.6Hz，2H，CH
2)，4.12(d，J＝11.6Hz，2H，CH
2)。
(R)-2,2 '-diformazan aldehyde radical-1,1 '-dinaphthalene (VII)
(10.1g, 32.2mmol) (100g 1.15mol) is suspended in the 300mL toluene VI, 25 ℃ of stirring reaction 18h with the Manganse Dioxide that activates.Filter, precipitation is washed with ethyl acetate 1L.Merging filtrate and washings, decompression removes solvent and gets and slightly produce VII 9.97g, and productive rate is greater than 99%.
(R)-2,2 '-diformyl-1,1 '-dinaphthalene (VIII)
To slightly produce VII (9.97g, 32.2mmol), NaH
2PO
42H
2O (15.01g, 96mmol) and the H of 20mL30%
2O
2Add successively in the tetrahydrofuran (THF) of 120mL, dropwise add the 120mL sodium chlorite aqueous solution under stirring, behind the stirring at room 1h, add 4g S-WAT reaction 10 minutes.Decompression removes solvent, adds 200mL 2N hydrochloric acid, uses ethyl acetate extraction.Merge organic phase, anhydrous sodium sulfate drying.Get crude product after removing solvent, can get pure VIII 10.4g, productive rate 94.3% through methylene dichloride/normal hexane recrystallization.
1H?NMR(400MHz，CDCl
3)：
(d，2H，J＝8.0Hz，Ar-H)，7.83(m，4H，Ar-H)，7.52(m，6H，Ar-H)。
Seven step overall yield of reaction 74.8%, optical purity of products is greater than 99%.
Embodiment 2
The optical purity of VI is measured with the HPLC method.Actual conditions is chirality CHIRALCEL AS-H post, and moving phase is Virahol: normal hexane=85: 15, flow velocity are 1mL/min.Enantiomorph retention time: 13.36min is (S) configuration, and 20.45min is (R) configuration.
VIII measures its optical purity with the HPLC method after being derivatized to isopropyl esters.Actual conditions is chirality CHIRALCEL OD-H post, and moving phase is Virahol: normal hexane=99: 1, flow velocity are 0.5mL/min.Enantiomorph retention time: 7.99min is (S) configuration, and 19.75min is (R) configuration.
Claims (1)
1. the preparation method of a chiral binaphthyl dicarboxylic acid is characterized in that comprising the steps:
(a) under the nitrogen protection, with 11.46 g, 40 mmol (
R)-dinaphthol and 17 mL, the triethylamine of 120 mmol is dissolved in methylene dichloride, slowly splashes into 18 mL, the trifluoromethyl sulfonic acid anhydride of 107 mmol, stirring at room 2h under-78 ℃; Reaction solution is poured 50 mL dilute hydrochloric acid into, tell organic layer after, the water layer dichloromethane extraction merges organic layer, uses saturated sodium bicarbonate and saturated common salt water washing respectively, anhydrous sodium sulfate drying, the evaporated under reduced pressure solvent gets slightly and produces
22.2g productive rate is greater than 99%;
(b) will slightly produce
22.0 g and 0.634 g, the NiCl of 1.2 mmol
2(dppp) be dissolved in ether, slowly splashing into concentration under-10 ℃ is the 160 mmol MeMgBr that the MeMgBr diethyl ether solution form of 3M exists, stirred overnight at room temperature; Reaction solution is removed nickel catalyzator with ether dilution after-filtration, and filtrate is respectively with 0.5 M dilute hydrochloric acid and saturated common salt washing, anhydrous sodium sulfate drying; The evaporated under reduced pressure solvent gets slightly and produces
11.3g productive rate is greater than 99%
;
(c) 11.26 g are slightly produced
, 18.6 g, the N-bromosuccinimide of 104 mmol and 0.81 g, the Diisopropyl azodicarboxylate of 5 mmol is dissolved in hexanaphthene, night is flow through in illumination next time; Cooling adds 40 mL ethyl acetate and 40 mL water in the reaction solution, stir 1h, and suction filtration is removed pale precipitation; Filtrate is used ethyl acetate extraction, merges the organic layer anhydrous sodium sulfate drying; The evaporated under reduced pressure solvent gets and slightly produces IV 16.5g, productive rate 94%
;
(d) 350 mL N add 16.5g successively and slightly produce in the dinethylformamide
, 19.6 g, the potassium acetate of 0.20 mol and 6.44 g, the Tetrabutyl amonium bromide of 0.20 mol, stirring and refluxing is spent the night; Cooling adds 500 mL ether in the reaction solution, suction filtration is removed white precipitate, and filtrate decompression removes solvent, gets slightly to produce
15.0g productive rate is greater than 99%;
(e) will slightly produce
15.0g and the KOH aqueous solution of 170 mL 50% adds in the 170 mL tetrahydrofuran (THF)s stirring and refluxing reaction 24h; Cooling, the reaction solution ether extraction merges the organic phase anhydrous sodium sulfate drying; Decompression removes solvent, gets slightly to produce
10.2g, productive rate 86%;
(f) 10.1 g, 32.2 mmol's
With 100 g, the Manganse Dioxide of 1.15 mol activation is suspended in the 300 mL toluene, and 25 ℃ of stirring reaction 18h filter, and precipitation is washed with ethyl acetate 1L; Merging filtrate and washings, decompression remove solvent and get slightly product
9.97 g, productive rate is greater than 99%;
(g) with 9.97 g, the thick product of 32.2 mmol
, 15.01 g, the NaH of 96 mmol
2PO
42H
2The H of O and 20 mL 30%
2O
2Add successively in the tetrahydrofuran (THF) of 120 mL, dropwise add the 120mL sodium chlorite aqueous solution under stirring, behind the stirring at room 1h, add 4g S-WAT reaction 10 minutes; Decompression removes solvent, adds 200 mL 2N hydrochloric acid, use ethyl acetate extraction, merges organic phase, anhydrous sodium sulfate drying, and removing behind the solvent must crude product, can get pure through methylene dichloride/normal hexane recrystallization
10.4 g, i.e. chiral binaphthyl dicarboxylic acid, productive rate 94.3%;
Seven step overall yield of reaction 74.8%, optical purity of products is greater than 99%.
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Non-Patent Citations (4)
| Title |
|---|
| Binaphthalene-Derived Iminium Salt Catalysts for Highly Enantioselective Asymmetric Epoxidation;Philip C. Bulman Page, et al.;《Eur. J. Org. Chem.》;20090603;第3413-3426页 * |
| Facile synthesis of enantiopure 1,1’-binaphthyl-2,2’-dicarboxylic acid via lipase-catalyzed kinetic resolution;Toshiyuki Furutani, et al.;《Tetrahedron: Asymmetry》;19991231;第10卷;第4763-4768页 * |
| Philip C. Bulman Page, et al..Binaphthalene-Derived Iminium Salt Catalysts for Highly Enantioselective Asymmetric Epoxidation.《Eur. J. Org. Chem.》.2009,第3413-3426页. |
| ToshiyukiFurutani et al..Facile synthesis of enantiopure 1 |
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