JP5262642B2 - Method for generating carbon-carbon bond - Google Patents
Method for generating carbon-carbon bond Download PDFInfo
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- JP5262642B2 JP5262642B2 JP2008308920A JP2008308920A JP5262642B2 JP 5262642 B2 JP5262642 B2 JP 5262642B2 JP 2008308920 A JP2008308920 A JP 2008308920A JP 2008308920 A JP2008308920 A JP 2008308920A JP 5262642 B2 JP5262642 B2 JP 5262642B2
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- carbon
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- catalyst
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- 239000011203 carbon fibre reinforced carbon Substances 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 51
- 239000003054 catalyst Substances 0.000 claims abstract description 38
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims abstract description 22
- 150000002894 organic compounds Chemical class 0.000 claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 17
- 239000002245 particle Substances 0.000 claims abstract description 12
- 238000005859 coupling reaction Methods 0.000 claims description 22
- 229910052763 palladium Inorganic materials 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 230000008878 coupling Effects 0.000 claims description 20
- 238000010168 coupling process Methods 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 150000003606 tin compounds Chemical class 0.000 claims description 5
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 30
- 239000000654 additive Substances 0.000 abstract description 8
- 238000006619 Stille reaction Methods 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000000926 separation method Methods 0.000 abstract description 3
- 230000003100 immobilizing effect Effects 0.000 abstract 1
- 238000010485 C−C bond formation reaction Methods 0.000 description 15
- XZIAFENWXIQIKR-UHFFFAOYSA-N ethyl 4-bromobenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C=C1 XZIAFENWXIQIKR-UHFFFAOYSA-N 0.000 description 15
- CRHIAMBJMSSNNM-UHFFFAOYSA-N tetraphenylstannane Chemical compound C1=CC=CC=C1[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 CRHIAMBJMSSNNM-UHFFFAOYSA-N 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 150000002941 palladium compounds Chemical class 0.000 description 10
- FFQZMOHAQYZTNR-UHFFFAOYSA-N ethyl 4-phenylbenzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C1=CC=CC=C1 FFQZMOHAQYZTNR-UHFFFAOYSA-N 0.000 description 7
- JZJWCDQGIPQBAO-UHFFFAOYSA-N 1-(4-iodophenyl)ethanone Chemical compound CC(=O)C1=CC=C(I)C=C1 JZJWCDQGIPQBAO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- -1 bis (2 Chemical class 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 4
- KCQJLTOSSVXOCC-UHFFFAOYSA-N tributyl(prop-1-ynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC KCQJLTOSSVXOCC-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- GPNDARIEYHPYAY-UHFFFAOYSA-N palladium(ii) nitrate Chemical compound [Pd+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O GPNDARIEYHPYAY-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000011949 solid catalyst Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RRHPTXZOMDSKRS-PHFPKPIQSA-L (1z,5z)-cycloocta-1,5-diene;dichloropalladium Chemical compound Cl[Pd]Cl.C\1C\C=C/CC\C=C/1 RRHPTXZOMDSKRS-PHFPKPIQSA-L 0.000 description 2
- QCZZSANNLWPGEA-UHFFFAOYSA-N 1-(4-phenylphenyl)ethanone Chemical group C1=CC(C(=O)C)=CC=C1C1=CC=CC=C1 QCZZSANNLWPGEA-UHFFFAOYSA-N 0.000 description 2
- SCCCFNJTCDSLCY-UHFFFAOYSA-N 1-iodo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(I)C=C1 SCCCFNJTCDSLCY-UHFFFAOYSA-N 0.000 description 2
- BAJQRLZAPXASRD-UHFFFAOYSA-N 4-Nitrobiphenyl Chemical group C1=CC([N+](=O)[O-])=CC=C1C1=CC=CC=C1 BAJQRLZAPXASRD-UHFFFAOYSA-N 0.000 description 2
- XOKDXPVXJWTSRM-UHFFFAOYSA-N 4-iodobenzonitrile Chemical compound IC1=CC=C(C#N)C=C1 XOKDXPVXJWTSRM-UHFFFAOYSA-N 0.000 description 2
- BPMBNLJJRKCCRT-UHFFFAOYSA-N 4-phenylbenzonitrile Chemical group C1=CC(C#N)=CC=C1C1=CC=CC=C1 BPMBNLJJRKCCRT-UHFFFAOYSA-N 0.000 description 2
- 238000004438 BET method Methods 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- JOXFGLUYWQJUQC-UHFFFAOYSA-N ethyl 4-(2-phenylethynyl)benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C#CC1=CC=CC=C1 JOXFGLUYWQJUQC-UHFFFAOYSA-N 0.000 description 2
- DYSXJBCEIBVGJU-UHFFFAOYSA-N ethyl 4-ethenylbenzoate Chemical compound CCOC(=O)C1=CC=C(C=C)C=C1 DYSXJBCEIBVGJU-UHFFFAOYSA-N 0.000 description 2
- IMEALXGKAYWLRF-UHFFFAOYSA-N ethyl 4-prop-1-ynylbenzoate Chemical compound CCOC(=O)C1=CC=C(C#CC)C=C1 IMEALXGKAYWLRF-UHFFFAOYSA-N 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 2
- GATUGNVDXMYTJX-UHFFFAOYSA-N methyl 4-phenylbenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=CC=C1 GATUGNVDXMYTJX-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
- 238000000790 scattering method Methods 0.000 description 2
- PYMPTRMDPJYTDF-UHFFFAOYSA-N tributyl(2-phenylethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#CC1=CC=CC=C1 PYMPTRMDPJYTDF-UHFFFAOYSA-N 0.000 description 2
- SYUVAXDZVWPKSI-UHFFFAOYSA-N tributyl(phenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC=C1 SYUVAXDZVWPKSI-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 206010012455 Dermatitis exfoliative Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical group [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 208000015322 bone marrow disease Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 231100000739 chronic poisoning Toxicity 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012834 electrophilic reactant Substances 0.000 description 1
- 231100000507 endocrine disrupting Toxicity 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 208000004526 exfoliative dermatitis Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 238000005470 impregnation Methods 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 150000002896 organic halogen compounds Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- INIOZDBICVTGEO-UHFFFAOYSA-L palladium(ii) bromide Chemical compound Br[Pd]Br INIOZDBICVTGEO-UHFFFAOYSA-L 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical class [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000036435 stunted growth Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical class CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
本発明は、脱離基を有する有機化合物と有機スズ化合物とのスティル(Stille)カップリングによる炭素−炭素結合の生成方法に関する。 The present invention relates to a method for producing a carbon-carbon bond by Stille coupling of an organic compound having a leaving group and an organotin compound.
スティルカップリングは、有機スズ化合物と有機求電子反応剤を用いた炭素−炭素結合形成反応である。この反応で使用される有機スズ化合物は、トリブチルスズ化合物に代表されるように内分泌撹乱作用をはじめとする毒性を持つことが知られており、反応生成物へのスズの残留が問題となるものの、1）様々なスズ化合物が合成可能で、多くの官能基と共存可能である、2）他の反応性有機金属と異なり水分や酸素に敏感ではない、3）容易に合成・保存できる、といった多くの利点を有している。また、スティルカップリング反応自体も比較的マイルドな中性条件で反応が進み、官能基受容性も高いため、医薬品や天然物合成に頻用される重要な反応である。これまでスティルカップリング反応は均一系パラジウム触媒を用いた反応が多く検討されてきたが（非特許文献１）、均一系パラジウム触媒は活性が高い反面、空気中で不安定であり、生成物からの触媒の分離・再利用が困難であるという欠点を有している。 Still coupling is a carbon-carbon bond forming reaction using an organotin compound and an organic electrophilic reactant. Organotin compounds used in this reaction are known to have toxicity including endocrine disrupting action as typified by tributyltin compounds, and although tin residue in the reaction product becomes a problem, 1) Various tin compounds can be synthesized and can coexist with many functional groups, 2) Unlike other reactive organic metals, it is not sensitive to moisture and oxygen, 3) Easy to synthesize and store, etc. Has the advantage of Still coupling reaction itself is an important reaction frequently used for synthesizing pharmaceuticals and natural products because the reaction proceeds under relatively mild neutral conditions and has high functional group acceptability. Until now, the Still Coupling reaction has been studied in many cases using a homogeneous palladium catalyst (Non-patent Document 1), but the homogeneous palladium catalyst has high activity but is unstable in the air. However, it is difficult to separate and reuse the catalyst.
この欠点を補うべく、最近になり、不均一系パラジウム触媒、例えばパラジウム炭素触媒の利用が検討されている。不均一系パラジウム触媒は、一般に均一系パラジウム触媒に比して活性が低いが、ヨウ化銅やトリフェニル砒素添加物などの添加により活性が高められることがわかってきている（非特許文献２）。しかしながら、銅やヒ素の過剰摂取は、多くの動物及び人体に対して有害であり、銅は肝硬変や発育不全、黄疸など、またヒ素では剥離性皮膚炎、骨髄障害、腎不全といった慢性中毒を引き起こす事が明らかとなっている。また、これらの添加物を使用することにより、生成物の分離・精製工程がさらに複雑になるという問題が発生する。 Recently, in order to compensate for this drawback, use of a heterogeneous palladium catalyst such as a palladium carbon catalyst has been studied. Heterogeneous palladium catalysts are generally less active than homogeneous palladium catalysts, but it has been found that the activity can be enhanced by the addition of copper iodide, triphenylarsenic additives, and the like (Non-patent Document 2). . However, excessive consumption of copper and arsenic is harmful to many animals and the human body, and copper causes cirrhosis, stunted growth, jaundice, etc., and arsenic causes chronic poisoning such as exfoliative dermatitis, bone marrow disorder, and renal failure Things are clear. Further, the use of these additives causes a problem that the product separation / purification process is further complicated.
そこで、生成物との分離の容易な固体触媒を用い、かつ、添加物を必要としない、スティルカップリングによる炭素−炭素結合の生成方法の開発が望まれていた。 Therefore, it has been desired to develop a method for producing a carbon-carbon bond by still coupling that uses a solid catalyst that can be easily separated from the product and does not require an additive.
本発明は、生成物との分離の容易な固体触媒であるパラジウム炭素触媒を用い、かつ基質である脱離基を有する有機化合物及び有機スズ化合物、溶媒及び上記パラジウム炭素触媒以外の添加物を必要とせず、且つ反応後の触媒の分離を容易にし、再利用を可能にする、スティルカップリングによる炭素−炭素結合生成方法を提供することを目的とする。 The present invention uses a palladium carbon catalyst that is a solid catalyst that can be easily separated from the product, and requires an organic compound and an organic tin compound having a leaving group as a substrate, a solvent, and an additive other than the palladium carbon catalyst. An object of the present invention is to provide a method for producing a carbon-carbon bond by still coupling, which facilitates separation of the catalyst after the reaction and enables reuse.
本発明者らは、炭素系固体触媒を鋭意検討した結果、高表面積を有する炭素粒子にパラジウムを固定したパラジウム炭素触媒を用いると、反応系中に他に添加物を存在させることなく、脱離基を有する有機化合物と有機スズ化合物とが、スティルカップリングにより炭素−炭素結合を生成する反応が効率よく進行することを見出し、本発明を完成するに至った。 As a result of intensive studies on carbon-based solid catalysts, the present inventors have found that when a palladium-carbon catalyst in which palladium is fixed to carbon particles having a high surface area is used, desorption without the presence of other additives in the reaction system. The present inventors have found that the organic compound having a group and the organotin compound efficiently undergo a reaction for generating a carbon-carbon bond by Still coupling, and have completed the present invention.
即ち、本発明は、比表面積1000m2/g以上の炭素粒子にパラジウムを固定したパラジウム炭素触媒の存在下で湿式にて、他に添加物（即ち、上記脱離基を有する有機化合物、上記有機スズ化合物、上記パラジウム炭素触媒及び溶媒以外の物質）を加えることなく、脱離基を有する有機化合物と有機スズ化合物とをスティルカップリングさせることを特徴とする炭素−炭素結合生成方法を提供するものである。 That is, the present invention is a wet process in the presence of a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more, and other additives (that is, an organic compound having the above leaving group, the above organic group). Provided is a carbon-carbon bond generation method characterized in that an organic compound having a leaving group and an organic tin compound are still coupled without adding a tin compound, a substance other than the palladium carbon catalyst and the solvent). It is.
本発明では、反応系中に触媒以外の添加物がなく、触媒も不均一系の触媒であることから、生成物とパラジウム炭素触媒を容易に分離することができるので、反応工程、装置、反応管理等を容易にすることができる。また、本発明で用いるパラジウム炭素触媒は、反応後に分離し回収した後の触媒活性の低下は僅かであり、繰り返しの再使用が可能であるため、生産コストを低減することができる。 In the present invention, since there are no additives other than the catalyst in the reaction system and the catalyst is also a heterogeneous catalyst, the product and the palladium carbon catalyst can be easily separated, so that the reaction process, apparatus, reaction Management and the like can be facilitated. In addition, the palladium carbon catalyst used in the present invention has a slight decrease in catalytic activity after being separated and recovered after the reaction, and can be reused repeatedly, so that the production cost can be reduced.
以下、本発明について更に詳細に説明する。
＜パラジウム炭素触媒＞
本発明で用いるパラジウム炭素触媒は、炭素粒子担体と、該炭素担体に固定されたパラジウムとを有するものである。
Hereinafter, the present invention will be described in more detail.
<Palladium carbon catalyst>
The palladium carbon catalyst used in the present invention has a carbon particle carrier and palladium fixed on the carbon carrier.
−担体−
本発明で用いるパラジウム炭素触媒の担体は炭素であり、好ましくは活性炭である。
-Carrier-
The support of the palladium carbon catalyst used in the present invention is carbon, preferably activated carbon.
担体の比表面積については、1000 m2/g以上が好ましく、1,000〜2,000 m2/gが更に好ましく、1100〜1500 m2/gであるのが特に好ましい。かかる比表面積を有する活性炭が最も好ましい。比表面積はＢＥＴ法で測定した値である。 The specific surface area of the carrier is preferably 1000 m 2 / g or more, more preferably 1,000 to 2,000 m 2 / g, and particularly preferably 1100 to 1500 m 2 / g. Most preferred is activated carbon having such a specific surface area. The specific surface area is a value measured by the BET method.
また、炭素粒子担体の粒径については特に限定されないが、メジアン径が0.5〜500μmの範囲であることが好ましく、5〜500μmが特に好ましい。メジアン径はレーザー散乱法により測定した値である。 The particle size of the carbon particle carrier is not particularly limited, but the median diameter is preferably in the range of 0.5 to 500 μm, particularly preferably 5 to 500 μm. The median diameter is a value measured by a laser scattering method.
−触媒の調製方法（炭素担体へのパラジウムの固定）−
炭素担体へのパラジウムの固定は、該炭素担体にパラジウムを含む溶液を接触させることにより行うことができる。
-Preparation method of catalyst (immobilization of palladium on carbon support)-
Immobilization of palladium on the carbon support can be performed by bringing the carbon support into contact with a solution containing palladium.
具体的には、本発明で用いるパラジウム炭素触媒は、例えば、パラジウム化合物を溶媒に溶解し、当該溶液中に炭素担体を投入し、パラジウム化合物を吸着または含浸させることにより行う。パラジウム化合物が塩化パラジウム酸など水溶性の場合には水を溶媒として用いることができる。パラジウム化合物が、ビス（２，４−ペンタンジオナト）パラジウムなど非水溶性の場合には、当該パラジウム化合物を溶解する有機溶媒を用いて吸着または含浸させることができる。パラジウムを吸着または含浸などの方法で担体に担持した触媒は、必要に応じて還元処理を実施してもよい。湿式で還元する場合には、メタノール、ホルムアルデヒド、蟻酸などの還元剤のほか、ガス状水素を用いることができる。乾式で還元する場合にはガス状水素を用いて行うが、水素ガスを窒素等の不活性ガスで希釈して使用することも可能である。 Specifically, the palladium carbon catalyst used in the present invention is performed, for example, by dissolving a palladium compound in a solvent, putting a carbon support into the solution, and adsorbing or impregnating the palladium compound. When the palladium compound is water-soluble such as chloropalladic acid, water can be used as a solvent. When the palladium compound is water-insoluble such as bis (2,4-pentanedionato) palladium, it can be adsorbed or impregnated using an organic solvent that dissolves the palladium compound. The catalyst in which palladium is supported on the support by a method such as adsorption or impregnation may be subjected to a reduction treatment as necessary. In the case of reduction in a wet manner, gaseous hydrogen can be used in addition to a reducing agent such as methanol, formaldehyde, formic acid or the like. When the reduction is performed in a dry manner, gaseous hydrogen is used, but it is also possible to dilute the hydrogen gas with an inert gas such as nitrogen.
こうして、通常、パラジウムが炭素担体に固定されたパラジウム炭素触媒が得られる。 Thus, a palladium carbon catalyst in which palladium is fixed on a carbon support is usually obtained.
触媒調製に用いる溶媒は、パラジウム化合物を溶解するものであれば特に制限されないが、水溶性のパラジウム化合物を用いる場合には水が好ましく、非水溶性で有機溶媒に可溶なパラジウム化合物の場合には、エタノール、アセトン、クロロホルム等の有機溶媒であって該パラジウム化合物を溶解するものが好適である。 The solvent used for preparing the catalyst is not particularly limited as long as it dissolves the palladium compound, but water is preferable when a water-soluble palladium compound is used, and in the case of a palladium compound that is water-insoluble and soluble in an organic solvent. Is preferably an organic solvent such as ethanol, acetone or chloroform which dissolves the palladium compound.
パラジウムの化合物としては、触媒調製工程に使用する溶媒に可溶性であれば特に限定されないが、硝酸パラジウム、硫酸パラジウム、テトラアンミンパラジウム塩化物、テトラアンミンパラジウム臭化物、テトラアンミンパラジウム硝酸塩、テトラアンミンパラジウム硫酸塩、塩化パラジウム酸等の水溶性化合物の他、ビス（２，４−ペンタンジオナト）パラジウム、ジクロロ（１，５−シクロオクタジエン）パラジウム、ジクロロビス（トリフェニルホスフィン）パラジウム、テトラキス（トリフェニルホスフィン）パラジウム、トリス（ジベンジリデンアセトン）二パラジウム等の有機溶媒に可溶な錯体が使用でき、硝酸パラジウム、塩化パラジウム酸、ジクロロ（１，５−シクロオクタジエン）パラジウムが好ましい。 The palladium compound is not particularly limited as long as it is soluble in the solvent used in the catalyst preparation step, but palladium nitrate, palladium sulfate, tetraammine palladium chloride, tetraammine palladium bromide, tetraammine palladium nitrate, tetraammine palladium sulfate, palladium chloride In addition to water-soluble compounds such as bis (2,4-pentanedionato) palladium, dichloro (1,5-cyclooctadiene) palladium, dichlorobis (triphenylphosphine) palladium, tetrakis (triphenylphosphine) palladium, tris ( A complex soluble in an organic solvent such as dibenzylideneacetone) dipalladium can be used, and palladium nitrate, chloropalladate, and dichloro (1,5-cyclooctadiene) palladium are preferred.
前記炭素担体１ｇ当たりのパラジウムの担持量は、特に制限されないが、パラジウム元素に換算して、通常、1.0μmol〜5mmol、好ましくは10μmol〜3mmol、特に好ましくは100μmol〜2mmolである。 The amount of palladium supported per 1 g of the carbon support is not particularly limited, but is usually 1.0 μmol to 5 mmol, preferably 10 μmol to 3 mmol, particularly preferably 100 μmol to 2 mmol in terms of palladium element.
＜脱離基を有する有機化合物と有機スズ化合物とのスティルカップリングによる炭素−炭素結合の生成方法＞
パラジウム炭素触媒の存在下、湿式にて、脱離基を有する有機化合物と有機スズ化合物とをカップリングさせることにより、炭素−炭素結合を生成させることができる。「湿式で」とは、通常、「溶媒の存在下で」を意味し、好ましくは「溶媒中で」を意味する。
<Method for generating carbon-carbon bond by Still coupling of organic compound having leaving group and organotin compound>
A carbon-carbon bond can be generated by coupling an organic compound having a leaving group and an organotin compound in the presence of a palladium carbon catalyst in a wet manner. “Wet” generally means “in the presence of a solvent”, preferably “in a solvent”.
本発明で反応の基質となる脱離基を有する有機化合物としては、通常、スティルカップ
リングに用いられる脱離基を有する有機化合物を使用できる。ここで、「脱離基を有する
有機化合物」とは、有機スズ化合物と反応して容易に離脱する基を有する有機化合物を云
うが、好ましくは下記一般式（Ｉ）：
R1-X （Ｉ）
（式中、R1は、置換のフェニル基であり、−ＣＯＯ（Ｃ１−Ｃ２０アルキル）基（例えば、メトキシカルボニル、エトキシカルボニル基等）の置換基を有しているフェニル基である。Ｘは臭素原子である。
As the organic compound having a leaving group which is a substrate for the reaction in the present invention, an organic compound having a leaving group which is usually used for Still coupling can be used. Here, the “organic compound having a leaving group” refers to an organic compound having a group that easily reacts with an organotin compound to leave, and preferably has the following general formula (I):
R 1 -X (I)
(Wherein, R 1 is a phenyl group substituted, - COO (C1-C20 alkyl) group (e.g., a phenyl group having a methoxy carbonyl, the substituents ethoxycarbonyl group, etc.) .X is Bromine atom.
本発明で反応のもう一方の基質となる有機スズ化合物は、通常、スティルカップリング
に用いられる有機スズ化合物を使用できるが、好ましくは下記一般式（ＩＩ）：
R2-Sn(R3)3 （ＩＩ）：
（式中、R２は、それぞれ置換基があってもよい、アルケニル基、アルキニル基を表し、R３は、アルキル基又はフェニル基を表す。）
で表される。
式（ＩＩ）中、R２は、好ましくは、炭素原子数２〜２０のアルケニル基、例えばビニル基、アリル基、プロペニル基、イソプロペニル基、２−メチル−1−プロペニル基、２−メチルアリル基、２−ブテニル基、１，３−ブタジエニル基等；炭素原子数２〜２０のアルキニル基、例えばエチニル基、プロピニル基、ブチニル基等；置換のフェニル基；フェニルアルケニル基、例えばフェニルプロペニル基であり、更に好ましくは、ビニル基、プロペニル基のようなアルケニル基；プロピニル基のようなアルキニル基；又は炭素原子数１〜２０のアルキル基、炭素原子数２〜２０のアルキニル基若しくは炭素原子数２〜２０のアリキニル基の置換基を有してもよいフェニル基である。
式（ＩＩ）中、R３は、好ましくは、炭素原子数１〜２０のアルキル基又はフェニル基
であり、更に好ましくはブチル基又はフェニル基である。
As the organotin compound that is the other substrate of the reaction in the present invention, an organotin compound that is generally used for Still coupling can be used, but preferably the following general formula (II):
R 2 -Sn (R 3 ) 3 (II):
(Wherein, R 2, there may be respective substituents, an alkenyl group, an Rukiniru group, R 3 represents an alkyl group or a phenyl group.)
It is represented by
In formula (II), R 2 is preferably, alkenyl Le group having 2 to 20 carbon atoms, such as vinyl group, allyl group, propenyl group, isopropenyl group, 2-methyl-1-propenyl group, 2-methylallyl , 2-butenyl, 1,3-butadienyl group or the like; an alkynyl group having 2 to 20 carbon atoms, such as ethynyl group, propynyl group, butynyl group or the like; substitution phenyl group; a phenyl alkenyl group, such as phenyl propenyl group More preferably, an alkenyl group such as a vinyl group or a propenyl group; an alkynyl group such as a propynyl group; or an alkyl group having 1 to 20 carbon atoms, an alkynyl group having 2 to 20 carbon atoms, or the number of carbon atoms It is a phenyl group which may have a substituent of 2 to 20 alkynyl groups.
In the formula (II), R 3 is preferably an alkyl group having 1 to 20 carbon atoms or a phenyl group, and more preferably a butyl group or a phenyl group.
式（Ｉ）の有機化合物と式（ＩＩ）の有機スズ化合物との使用割合は、モル比で、１０：１〜１：１０であり、好ましくは１：１〜１：３である。 The use ratio of the organic compound of the formula (I) and the organotin compound of the formula (II) is 10: 1 to 1:10, preferably 1: 1 to 1: 3 in molar ratio.
本発明で用いる触媒は、反応体の一つである有機ハロゲン化合物に対して、パラジウムとして、通常、0.01〜20モル％の間で用いられ、好ましくは0.1〜10モル％、より好ましくは0.5〜5モル％の範囲で用いられる。 The catalyst used in the present invention is usually used in an amount of 0.01 to 20 mol%, preferably 0.1 to 10 mol%, more preferably 0.5 to 0.5 mol as palladium with respect to the organic halogen compound that is one of the reactants. It is used in the range of 5 mol%.
炭素−炭素結合生成反応に用いる溶媒は、特に制限されないが、好ましくは、テトラヒドロフラン、N,N-ジメチルホルムアミド、ジメチルアセトアミド、N-メチルピロリドンなどの極性有機溶媒；またはこれらの組み合わせであり、N,N-ジメチルホルムアミド又はN-メチルピロリドンが特に好ましい。 The solvent used for the carbon-carbon bond formation reaction is not particularly limited, but is preferably a polar organic solvent such as tetrahydrofuran, N, N-dimethylformamide, dimethylacetamide, N-methylpyrrolidone; or a combination thereof; N-dimethylformamide or N-methylpyrrolidone is particularly preferred.
この炭素−炭素結合生成反応は、湿式で、例えば、空気雰囲気中または窒素、アルゴン等の不活性ガスの雰囲気中で行われるが、好ましくは不活性ガス雰囲気中で、通常、室温から200℃の温度領域で１〜48時間程度で行われる。反応温度は80〜120℃であることが特に好ましい。 This carbon-carbon bond formation reaction is performed in a wet manner, for example, in an air atmosphere or an atmosphere of an inert gas such as nitrogen or argon, but preferably in an inert gas atmosphere, usually at room temperature to 200 ° C. It takes about 1 to 48 hours in the temperature range. The reaction temperature is particularly preferably 80 to 120 ° C.
以下に本発明の実施例を示すが、本発明は以下の実施例に限定されるものではない。以下の記載において、担体の比表面積は、株式会社島津製作所製、比面積自動測定装置「フローソーブＩＩ２３００形（商品名）」を用いてＢＥＴ法により測定された値であり、粒径は、日機装株式会社製、レーザー粒度測定装置「ＭＩＣＲＯＴＲＡＣ ＨＲＡ」（商品名）を用いてレーザー散乱法で測定されたメジアン径を意味する。 Examples of the present invention are shown below, but the present invention is not limited to the following examples. In the following description, the specific surface area of the carrier is a value measured by the BET method using an automatic specific area measurement device “Flowsorb II2300 (trade name)” manufactured by Shimadzu Corporation, and the particle size is Nikkiso Co., Ltd. It means the median diameter measured by the laser scattering method using a company-made laser particle size measuring device “MICROTRAC HRA” (trade name).
＜実施例１＞
（４−ブロモ安息香酸エチルとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビフェニルカルボン酸エチルの合成）
４−ブロモ−安息香酸エチル0.25mmolとテトラフェニルスズ0.50mmolをアルゴン気流下、N-メチルピロリドン1mlに溶解させた。この溶液に10質量％パラジウムカーボン粉末触媒（担体の比表面積1190m2/g、メジアン径：26μm、炭素粒子担体１ｇ当たりのパラジウムの担持量：パラジウム元素に換算して0.94mmol、エヌ・イー ケムキャット（株）製）をパラジウムとして12.5μmol（４−ブロモ−安息香酸エチルに対して５モル％）を加え、アルゴン雰囲気下、90℃で24時間攪拌した。反応後、飽和フッ化カリウム溶液を加え攪拌した後、ジエチルエーテルと水を加え、触媒をろ過分離した。ジエチルエーテル層を食塩水で洗浄、乾燥した後、シリカゲルクロマト精製（ヘキサン：酢酸エチル＝80：1）して、４−ビフェニルカルボン酸エチルを得た。反応に使用した４−ブロモ安息香酸エチル対する４−ビフェニルカルボン酸エチルの収率は87%であった。
<Example 1>
(Synthesis of ethyl 4-biphenylcarboxylate by carbon-carbon bond formation reaction by still coupling of ethyl 4-bromobenzoate and tetraphenyltin)
0.25 mmol of ethyl 4-bromo-benzoate and 0.50 mmol of tetraphenyltin were dissolved in 1 ml of N-methylpyrrolidone under an argon stream. In this solution, a 10% by mass palladium carbon powder catalyst (specific surface area of support 1190 m 2 / g, median diameter: 26 μm, supported amount of palladium per gram of carbon particle support: 0.94 mmol in terms of palladium element, N Chemcat ( 12.5 μmol (5 mol% with respect to ethyl 4-bromo-benzoate) was added as palladium, and the mixture was stirred at 90 ° C. for 24 hours under an argon atmosphere. After the reaction, a saturated potassium fluoride solution was added and stirred, diethyl ether and water were added, and the catalyst was separated by filtration. The diethyl ether layer was washed with brine, dried, and purified by silica gel chromatography (hexane: ethyl acetate = 80: 1) to give ethyl 4-biphenylcarboxylate. The yield of ethyl 4-biphenylcarboxylate relative to ethyl 4-bromobenzoate used in the reaction was 87%.
＜実施例２＞
（４’−ヨードアセトフェノンとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−アセチルビフェニルの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４’−ヨードアセトフェノンを等モル量（0.25mmol）用いた以外は実施例１と同様にして、４−アセチルビフェニルを得た。収率は65%であった。
<Example 2>
(Synthesis of 4-acetylbiphenyl by carbon-carbon bond formation reaction by Still coupling of 4'-iodoacetophenone and tetraphenyltin)
In Example 1, 4-acetylbiphenyl was obtained in the same manner as in Example 1 except that an equimolar amount (0.25 mmol) of 4′-iodoacetophenone was used instead of ethyl 4-bromobenzoate. The yield was 65%.
＜実施例３＞
（４−ヨードベンゾニトリルとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−シアノビフェニルの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４−ヨードベンゾニトリルを等モル量（0.25mmol）用いた以外は実施例１と同様にして、４−シアノビフェニルを得た。収率は44%であった。
<Example 3>
(Synthesis of 4-cyanobiphenyl by carbon-carbon bond formation reaction by Still coupling of 4-iodobenzonitrile and tetraphenyltin)
In Example 1, 4-cyanobiphenyl was obtained in the same manner as in Example 1, except that equimolar amount (0.25 mmol) of 4-iodobenzonitrile was used instead of ethyl 4-bromobenzoate. The yield was 44%.
＜実施例４＞
（４−ヨード安息香酸メチルとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビフェニルカルボン酸メチルの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４−ヨード安息香酸メチルを等モル量（0.25mmol）用いた以外は実施例１と同様にして、４−ビフェニルカルボン酸メチルを得た。収率は55%であった。
<Example 4>
(Synthesis of methyl 4-biphenylcarboxylate by carbon-carbon bond formation reaction by still coupling of methyl 4-iodobenzoate and tetraphenyltin)
In Example 1, methyl 4-biphenylcarboxylate was obtained in the same manner as in Example 1 except that equimolar amount (0.25 mmol) of methyl 4-iodobenzoate was used instead of ethyl 4-bromobenzoate. The yield was 55%.
＜実施例５＞
（４−ヨードニトロベンゼンとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ニトロビフェニルの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４−ヨードニトロベンゼンを等モル量（0.25mmol）用いた以外は実施例１と同様にして、４−ニトロビフェニルを得た。収率は44%であった。
<Example 5>
(Synthesis of 4-nitrobiphenyl by carbon-carbon bond formation reaction by Still coupling of 4-iodonitrobenzene and tetraphenyltin)
In Example 1, 4-nitrobiphenyl was obtained in the same manner as in Example 1, except that equimolar amount (0.25 mmol) of 4-iodonitrobenzene was used instead of ethyl 4-bromobenzoate. The yield was 44%.
＜実施例６＞
（４−ブロモ安息香酸エチルとトリブチルフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビフェニルカルボン酸エチルの合成）
実施例１において、テトラフェニルスズの代わりにトリブチルフェニルスズを等モル量（0.25mmol）用いた以外は実施例１と同様にして４−ビフェニルカルボン酸エチルを得た。収率は85%であった。
<Example 6>
(Synthesis of ethyl 4-biphenylcarboxylate by carbon-carbon bond formation reaction by Still coupling of ethyl 4-bromobenzoate and tributylphenyltin)
In Example 1, ethyl 4-biphenylcarboxylate was obtained in the same manner as in Example 1 except that an equimolar amount (0.25 mmol) of tributylphenyltin was used instead of tetraphenyltin. The yield was 85%.
＜実施例７＞
（４−ブロモ安息香酸エチルとトリブチル（フェニルエチニル）スズとのスティルカップリングによる炭素−炭素結合生成反応による、４−フェニルエチニル安息香酸エチルの合成）
実施例１において、テトラフェニルスズの代わりにトリブチル（フェニルエチニル）スズを等モル量（0.50mmol）用いた以外は実施例１と同様にして４−フェニルエチニル安息香酸エチルを得た。収率は22%であった。
<Example 7>
(Synthesis of ethyl 4-phenylethynylbenzoate by carbon-carbon bond formation reaction by still coupling of ethyl 4-bromobenzoate and tributyl (phenylethynyl) tin)
In Example 1, ethyl 4-phenylethynylbenzoate was obtained in the same manner as in Example 1 except that an equimolar amount (0.50 mmol) of tributyl (phenylethynyl) tin was used instead of tetraphenyltin. The yield was 22%.
＜実施例８＞
（４−ブロモ安息香酸エチルとトリブチル（１−プロピニル）スズとのスティルカップリングによる炭素−炭素結合生成反応による、４−プロピニル安息香酸エチルの合成）
実施例１において、テトラフェニルスズの代わりにトリブチル（１−プロピニル）スズを等モル量（0.50mmol）用いた以外は実施例１と同様にして４−プロピニル安息香酸エチルを得た。収率は85%であった。
<Example 8>
(Synthesis of ethyl 4-propynylbenzoate by carbon-carbon bond formation reaction by still coupling of ethyl 4-bromobenzoate and tributyl (1-propynyl) tin)
In Example 1, ethyl 4-propynylbenzoate was obtained in the same manner as in Example 1 except that an equimolar amount (0.50 mmol) of tributyl (1-propynyl) tin was used instead of tetraphenyltin. The yield was 85%.
＜実施例９＞
（４−ブロモ安息香酸エチルとトリブチル（ビニル）スズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビニル安息香酸エチルの合成）
実施例１において、テトラフェニルスズの代わりにトリブチル（ビニル）スズを等モル量（0.50mmol）用いた以外は実施例１と同様にして４−ビニル安息香酸エチルを得た。収率は85%であった。
<Example 9>
(Synthesis of ethyl 4-vinylbenzoate by carbon-carbon bond formation reaction by still coupling of ethyl 4-bromobenzoate and tributyl (vinyl) tin)
In Example 1, ethyl 4-vinylbenzoate was obtained in the same manner as in Example 1 except that an equimolar amount (0.50 mmol) of tributyl (vinyl) tin was used instead of tetraphenyltin. The yield was 85%.
＜実施例１０＞
（４’−ヨードアセトフェノンとトリブチル（１−プロピニル）スズとのスティルカップリングによる炭素−炭素結合生成反応による、４−プロピニルアセトフェノンの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４’−ヨードアセトフェノンを等モル量（0.25mmol）、また、テトラフェニルスズの代わりにトリブチル（１−プロピニル）スズを等モル量（0.50mmol）用いた以外は実施例１と同様にして４−プロピニルアセトフェノンを得た。収率は55%であった。
<Example 10>
(Synthesis of 4-propynylacetophenone by carbon-carbon bond formation reaction by Stille coupling of 4'-iodoacetophenone and tributyl (1-propynyl) tin)
In Example 1, an equimolar amount (0.25 mmol) of 4′-iodoacetophenone instead of ethyl 4-bromobenzoate and an equimolar amount (0.50 mmol) of tributyl (1-propynyl) tin instead of tetraphenyltin ) 4-propynylacetophenone was obtained in the same manner as in Example 1 except that it was used. The yield was 55%.
＜実施例１１＞
（４’−ヨードアセトフェノンとトリブチル（ビニル）スズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビニルアセトフェノンの合成）
実施例１において、４−ブロモ安息香酸エチルの代わりに４’−ヨードアセトフェノンを等モル量（0.25mmol）、また、テトラフェニルスズの代わりにトリブチル（ビニル）スズを等モル量（0.50mmol）用いた以外は実施例１と同様にして４−ビニルアセトフェノンを得た。収率は36%であった。
<Example 11>
(Synthesis of 4-vinylacetophenone by carbon-carbon bond formation reaction by Still coupling of 4'-iodoacetophenone and tributyl (vinyl) tin)
In Example 1, 4'-iodoacetophenone is used in an equimolar amount (0.25 mmol) instead of ethyl 4-bromobenzoate, and tributyl (vinyl) tin is used in an equimolar amount (0.50 mmol) instead of tetraphenyltin. 4-vinylacetophenone was obtained in the same manner as in Example 1 except that. The yield was 36%.
＜比較例１＞
（パラジウムカーボン触媒（担体の比表面積850m２/g）を用いた４−ブロモ安息香酸エチルとテトラフェニルスズとのスティルカップリングによる炭素−炭素結合生成反応による、４−ビフェニルカルボン酸エチルの合成）
実施例１において、10質量％パラジウムカーボン粉末触媒（担体の比表面積1190m2/g）に代え、同じくエヌ・イー ケムキャット（株）製、10質量％パラジウムカーボン粉末触媒（担体の比表面積850m2/g）を用いた以外は実施例１と同様にして、４−ビフェニルカルボン酸エチルを得た。収率は43%であった。
<Comparative Example 1>
(Synthesis of ethyl 4-biphenylcarboxylate by carbon-carbon bond formation reaction by Still coupling of ethyl 4-bromobenzoate and tetraphenyltin using palladium carbon catalyst (specific surface area of carrier: 850 m 2 / g))
In Example 1, instead of the 10 wt% palladium carbon powder catalyst (a specific surface area of 1190m 2 / g of support), likewise NE Chemcat Co., 10 wt% palladium carbon powder catalyst (specific surface area of the support 850 meters 2 / Ethyl 4-biphenylcarboxylate was obtained in the same manner as in Example 1 except that g) was used. The yield was 43%.
Claims (5)
前記有機化合物は、下記一般式（Ｉ）：
R 1 -X （Ｉ）
（式中、R 1 は、置換のフェニル基であり、−ＣＯＯ（Ｃ１−Ｃ２０アルキル）基の置換基を有しているフェニル基を表し、Xは、臭素原子を表す。）で表される有機化合物であり、
前記有機スズ化合物は、下記一般式（ＩＩ）：
R 2 -Sn(R 3 ) 3 （ＩＩ）：
（式中、R ２ は、それぞれ置換基があってもよい、アルケニル基、アルキニル基を表し、R ３ は、アルキル基又はフェニル基を表す。）で表される有機スズ化合物であることを特徴とする炭素−炭素結合生成方法。 A carbon-carbon bond generation method in which an organic compound having a leaving group and an organic tin compound are still coupled in a wet manner in the presence of a palladium carbon catalyst in which palladium is fixed to carbon particles having a specific surface area of 1000 m 2 / g or more. There,
The organic compound has the following general formula (I):
R 1 -X (I)
(Wherein R 1 is a substituted phenyl group, represents a phenyl group having a substituent of —COO (C 1 -C 20 alkyl) group, and X represents a bromine atom). An organic compound,
The organotin compound has the following general formula (II):
R 2 -Sn (R 3 ) 3 (II):
(Wherein R 2 represents an alkenyl group or an alkynyl group, each of which may have a substituent, and R 3 represents an alkyl group or a phenyl group). A carbon-carbon bond generation method
素結合生成方法。 The method for producing a carbon-carbon bond according to claim 1, wherein still coupling is performed without adding a substance other than the organic compound having the leaving group, the organotin compound, the palladium carbon catalyst, and the solvent.
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