CN101500978B - 制备2,2,3-三甲基环戊-3-烯甲醛（龙脑醛）的方法 - Google Patents
制备2,2,3-三甲基环戊-3-烯甲醛（龙脑醛）的方法 Download PDFInfo
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- CN101500978B CN101500978B CN2007800299929A CN200780029992A CN101500978B CN 101500978 B CN101500978 B CN 101500978B CN 2007800299929 A CN2007800299929 A CN 2007800299929A CN 200780029992 A CN200780029992 A CN 200780029992A CN 101500978 B CN101500978 B CN 101500978B
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- 150000001299 aldehydes Chemical class 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 11
- KUSHNIVDXXIKCE-UHFFFAOYSA-N 2,2,3-trimethylcyclopent-3-ene-1-carbaldehyde Chemical compound CC1=CCC(C=O)C1(C)C KUSHNIVDXXIKCE-UHFFFAOYSA-N 0.000 title description 3
- 239000002904 solvent Substances 0.000 claims abstract description 18
- OGCGGWYLHSJRFY-UHFFFAOYSA-N alpha-campholenaldehyde Chemical compound CC1=CCC(CC=O)C1(C)C OGCGGWYLHSJRFY-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- OGCGGWYLHSJRFY-SECBINFHSA-N (+)-alpha-Campholenal Natural products CC1=CC[C@H](CC=O)C1(C)C OGCGGWYLHSJRFY-SECBINFHSA-N 0.000 claims abstract description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052802 copper Inorganic materials 0.000 claims abstract description 8
- 239000010949 copper Substances 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 11
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 229910052760 oxygen Chemical group 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229910021592 Copper(II) chloride Inorganic materials 0.000 claims description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003880 polar aprotic solvent Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- -1 for example Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- XTVVROIMIGLXTD-UHFFFAOYSA-N copper(II) nitrate Chemical compound [Cu+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O XTVVROIMIGLXTD-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- GZKULOHNKLYWIC-VOTSOKGWSA-N 4-[(e)-2-(2,2,3-trimethylcyclopent-3-en-1-yl)ethenyl]morpholine Chemical compound CC1(C)C(C)=CCC1\C=C\N1CCOCC1 GZKULOHNKLYWIC-VOTSOKGWSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- JJLJMEJHUUYSSY-UHFFFAOYSA-L copper(II) hydroxide Inorganic materials [OH-].[OH-].[Cu+2] JJLJMEJHUUYSSY-UHFFFAOYSA-L 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- NYQGWGPJHCJZSF-UHFFFAOYSA-N 2,2,3-trimethylcyclopent-3-en-1-one Chemical compound CC1=CCC(=O)C1(C)C NYQGWGPJHCJZSF-UHFFFAOYSA-N 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical compound [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021593 Copper(I) fluoride Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021594 Copper(II) fluoride Inorganic materials 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical class [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- PIBRPUANPFZKJQ-UHFFFAOYSA-N [Cu+].N#CSC#N Chemical compound [Cu+].N#CSC#N PIBRPUANPFZKJQ-UHFFFAOYSA-N 0.000 description 1
- OLBVUFHMDRJKTK-UHFFFAOYSA-N [N].[O] Chemical compound [N].[O] OLBVUFHMDRJKTK-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 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
- KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- OXFZSJOUPRCPJO-UHFFFAOYSA-N copper ethyl 3-oxobutanoate Chemical compound [Cu+2].CCOC(=O)[CH-]C(C)=O.CCOC(=O)[CH-]C(C)=O OXFZSJOUPRCPJO-UHFFFAOYSA-N 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- XCJYREBRNVKWGJ-UHFFFAOYSA-N copper(II) phthalocyanine Chemical compound [Cu+2].C12=CC=CC=C2C(N=C2[N-]C(C3=CC=CC=C32)=N2)=NC1=NC([C]1C=CC=CC1=1)=NC=1N=C1[C]3C=CC=CC3=C2[N-]1 XCJYREBRNVKWGJ-UHFFFAOYSA-N 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
- 229910001497 copper(II) tetrafluoroborate Inorganic materials 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- BMRUOURRLCCWHB-UHFFFAOYSA-M copper(i) fluoride Chemical compound [Cu]F BMRUOURRLCCWHB-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- GWFAVIIMQDUCRA-UHFFFAOYSA-L copper(ii) fluoride Chemical compound [F-].[F-].[Cu+2] GWFAVIIMQDUCRA-UHFFFAOYSA-L 0.000 description 1
- YRNNKGFMTBWUGL-UHFFFAOYSA-L copper(ii) perchlorate Chemical compound [Cu+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O YRNNKGFMTBWUGL-UHFFFAOYSA-L 0.000 description 1
- MAUZTCHAIPUZJB-OLXYHTOASA-L copper;(2r,3r)-2,3-dihydroxybutanedioate;hydrate Chemical compound O.[Cu+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O MAUZTCHAIPUZJB-OLXYHTOASA-L 0.000 description 1
- ZKXWKVVCCTZOLD-FDGPNNRMSA-N copper;(z)-4-hydroxypent-3-en-2-one Chemical compound [Cu].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O ZKXWKVVCCTZOLD-FDGPNNRMSA-N 0.000 description 1
- HFDWIMBEIXDNQS-UHFFFAOYSA-L copper;diformate Chemical compound [Cu+2].[O-]C=O.[O-]C=O HFDWIMBEIXDNQS-UHFFFAOYSA-L 0.000 description 1
- AEJIMXVJZFYIHN-UHFFFAOYSA-N copper;dihydrate Chemical compound O.O.[Cu] AEJIMXVJZFYIHN-UHFFFAOYSA-N 0.000 description 1
- QYCVHILLJSYYBD-UHFFFAOYSA-L copper;oxalate Chemical compound [Cu+2].[O-]C(=O)C([O-])=O QYCVHILLJSYYBD-UHFFFAOYSA-L 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- ODXGUKYYNHKQBC-UHFFFAOYSA-N n-(pyrrolidin-3-ylmethyl)cyclopropanamine Chemical compound C1CNCC1CNC1CC1 ODXGUKYYNHKQBC-UHFFFAOYSA-N 0.000 description 1
- PXSXRABJBXYMFT-UHFFFAOYSA-N n-hexylhexan-1-amine Chemical compound CCCCCCNCCCCCC PXSXRABJBXYMFT-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229940063729 oxygen 80 % Drugs 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/38—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
- C07C47/40—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings with a five-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Catalysts (AREA)
Abstract
一种在铜催化剂和溶剂的存在下由龙脑烯醛出发制备龙脑醛的方法。
Description
公开了制备2，2，3-三甲基-3-环戊烯-1-甲醛(也公知为龙脑醛)的方法。
迄今为止，龙脑醛由昂贵的环氧-马鞭草烯酮来制备，例如，如Bessiere-Chretien等，Comptes Rendus des Seances de l′Academie desSciences，Serie C：Sciences Chimiques(1971)，273(3)，第272-275页，或者Amri等，Journal de la Societe Chimique de Tunisie(1983)，10，第25-32页中所述。
本发明者现已发现了一种由龙脑烯醛(2-(2，2，3-三甲基环戊-3-烯基)乙醛)(其是相对廉价的散装化学品)出发以高产率制备龙脑醛的新方法，获得相对廉价的龙脑醛，其又可以用于制备新类型的分子。例如，其可以用于制备多种新的香料成分。另外，通过使用相对廉价的原材料，可以抑制一些香料成分生产的总成本。
由此，本发明提供了制备龙脑醛的方法，包括：
A)使龙脑烯醛与式(I)的胺反应：
其中，
R1和R2独立地选自C1-C6烷基或苄基；或者
R1和R2与它们所连接的氮原子一起形成含有4-7个碳原子和无或一个选自氮和氧的其它杂原子的环，例如吗啉、吡咯烷和哌啶；
B)将A)获得的产物在铜催化剂和溶剂的存在下用氧进行处理以制得龙脑醛，条件是该溶剂不是氯化溶剂。
关于式(I)化合物使用的“烷基”，除非相反地指出，否则均表示线性或支化烷基、饱和或不饱和烷基和环烷基，如甲基、乙基、丁基、己基和环己基。
依据本发明，将龙脑烯醛转化为相应的烯胺，如果必要的话在本领域技术人员公知的迪安-斯达克(Dean-Stark)条件下。随后利用氧或空气和铜催化剂将其氧化降解为相应的龙脑醛。最后的步骤在对于反应进行来说必需的溶剂的存在下进行。溶剂选择的关键参数是初始烯胺的稳定性。由此，质子溶剂通常是不理想的。另外，必需至少小部分的铜催化剂可溶于该溶剂。该溶剂可以选自仲酰胺类，如二甲基甲酰胺或N-甲基-吡咯烷酮等；和腈类，如乙腈、丙腈和丁腈。其还可以是醚如甲基叔丁基醚、四氢呋喃、1，3-二氧六环、1，2-二甲氧基乙烷、二甘醇二甲醚等。但是，虽然氯化溶剂具有溶解一些铜催化剂的能力，但是在氯化溶剂的存在下观察到极少或者无转化。特别优选极性非质子溶剂如乙腈、二甲基甲酰胺和N-甲基-吡咯烷酮。
任意铜(I)或铜(II)化合物可以用于催化该反应。下面示例地给出了一列这种盐，但并非限定该选择。
铜(I)化合物，如乙酸亚铜(I)、溴化亚铜(I)、氯化亚铜(I)、碘化亚铜(I)、氟化亚铜(I)、氰化亚铜(I)、氧化亚铜(I)、硫氰化亚铜(I)，和络合化合物，如六氟磷酸四(乙腈)铜(I)。
铜(II)化合物，如乙酸铜(II)、乙酰丙酮化铜(II)、溴化铜(II)、氯化铜(II)、乙基乙酰乙酸铜(II)、氟化铜(II)、氧化铜(II)、硝酸铜(II)、草酸铜(II)、高氯酸铜(II)、酞菁铜(II)、硫酸铜(II)、酒石酸铜(II)、四氟硼酸铜(II)、氢氧化铜(II)、D-葡糖酸铜(II)和甲酸铜(II)。
优选的催化剂为氯化亚铜(I)和氯化铜(II)。
反应温度取决于采用的溶剂且可以在反应混合物的固化温度与沸腾温度之间。优选的反应温度为0℃-50℃且最优选的温度为约20-约30℃。
虽然空气(天然的或合成的：20％氧气80％氮气)足以实现期望的反应，但是优选纯氧气且最有效。但是，原则上可以使用任意氧气-氮气混合物。
式(I)的胺包括但并非限定于二甲基胺、二乙基胺、二丁基胺、二己基胺、二环己基胺、N-甲基-苄基胺、吗啉、吡咯烷和哌啶。
采用本文中上述的通用方法，实质上观察不到龙脑烯醛手性中心的外消旋化。例如，由约30％ee的(S)-(+)龙脑烯醛出发获得至少约27％ee的(R)-(-)龙脑醛，且由约80％ee的(R)-(-)龙脑烯醛出发获得至少约81％ee的(S)-(+)龙脑醛。
现在参照如下非限定性实施例进一步描述本发明。这些实施例仅是出于举例说明的目的，且可以理解的是本领域技术人员可以进行改变和改进。
实施例
A)4-((1E)-2-(2，2，3-三甲基环戊-3-烯基)乙烯基)吗啉
工序A
使龙脑烯醛(138g，0.9mol)和吗啉(95.7g，1.1mol)的混合物溶解于环己烷(400ml)中，并加入催化量的p-甲苯磺酸(1g)。将混合物加热到回流同时搅拌。在迪安-斯达克条件下，在3小时内收集到约18g水。冷却到室温之后，将混合物用水(200ml)清洗、在硫酸钠之上干燥并在真空下浓缩以提供粗吗啉烯胺(235g)。通过在减压下5cm-Vigreux柱子上蒸馏对其进行纯化，由此提供浅黄色油状的目标化合物(186g)，沸点110℃(0.1mabr)。
1H-NMR：δ5.80(1H，d，J＝13.8，＝CHN)，5.25-5.23(1H，m，＝CH)，4.48(1H，dd，J＝13.8，9.2，＝CH)，3.73(4H，表观t，J＝4.9，2x OCH2)，2.80(4H，表观t，J＝4.9，2x NCH2)，2.27-2.21(2H，m，CH和CHH)，2.08-1.97(1H，m，CHH)，1.62-1.60(3H，m，Me)，0.92(3H，s，Me)，和0.74(3H，s，Me)。
13C-NMR：δ148.3(s)，139.8(d)，121.6(d)，103.2(d)，66.5(t)，52.6(d)，49.6(t)，47.7(s)，36.9(t)，25.1(q)，20.2(q)，和12.9(q)。
MS：221(M+，100)，206(93)，178(13)，139(33)，126(25)，119(32)，113(29)，91(24)，79(16)，67(14)，55(16)，41(24)。
工序B
烧瓶中装入龙脑烯醛(1200g，6.9mol)并在搅拌下加入吗啉(600g，6.9mol)。混合物放热且升温到75℃，同时水分离。将混合物转移到分液漏斗中并除去水(105ml)。通过10cm-Vigruex柱子将粗产物蒸馏以提供浅黄色油状的期望产物(1240g)，沸点118-120℃(0.2mbar)。
B)龙脑醛(2，2，3-三甲基环戊-3-烯甲醛)
使4-((1E)-2-(2，2，3-三甲基环戊-3-烯基)乙烯基)吗啉(45g，0.2mol)溶解于溶剂(参见下表，200ml)中并加入铜催化剂(参见下表，0.01mol)。随后，在25-30℃和强力搅拌下使氧气流(或者空气，参见下表)从溶液中起泡3.5小时，之后将初始吗啉烯胺全部消耗。将混合物倒入冰/水(500ml)中并采用己烷或戊烷(3×250ml)进行萃取。将结合的有机相用氯化铵溶液(饱和水溶液，250ml)清洗、在硫酸钠之上干燥并在真空下浓缩，由此获得浅黄色到浅绿色液体的粗产物。使其通过6cm-Widmer柱子在减压下蒸馏，由此提供极浅黄色油状的所需龙脑醛，沸点67-68℃(～15mbar)。
1H-NMR：δ9.76(1H，d，J＝3.2，CHO)，5.26-5.24(1H，m，＝CH)，2.69-2.65(1H，m，CH)，2.63-2.55(1H，m，CHH)，2.41-2.31(1H，m，CHH)，1.63-1.60(3H，m，Me)，1.21(3H，s，Me)，和1.00(3H，s，Me)。
13C-NMR：δ204.5(d)，146.8(s)，121.0(d)，61.5(d)，48.9(s)，29.3(t)，25.6(q)，21.6(q)，和11.7(q)。
MS：138(M+，26)，123(58)，109(22)，95(100)，79(20)，67(48)，55(28)，41(23)。
由(R)-龙脑烯醛(～80％ee)出发时，旋光度为：[α]D 22＝+9.8°(EtOH中5.09)。
由(S)-龙脑烯醛(～30％ee)出发时，旋光度为：[α]D 22＝-3.8°(EtOH中5.01)。
| 溶剂 | 催化剂 | 氧 | 产物 | 备注 |
| 乙腈 | CuCl | 100％ | 22.5g | 完全反应(clean reaction) |
| 乙腈 | CuCl2＊2H2O | 100％ | 20.2g | 完全反应 |
| 乙腈 | CuCl | 20％(空气) | 未分离 | 极慢反应 |
| 二甲基甲酰胺 | CuCl | 100％ | 22.4g | 完全反应 |
| N-甲基吡咯烷酮 | CuCl | 100％ | 21.6g | 完全反应 |
| 甲基叔丁基醚 | CuCl | 100％ | 6.5g | 缓慢反应＊ |
| 氯仿 | CuCl | 100％ | - | 无反应 |
| 二氯甲烷 | CuCl | 100％ | - | 无反应 |
| 无溶剂 | CuCl | 100％ | - | 无反应 |
＊作为副产物分离出1.2g纯2，2，3-三甲基-3-环戊烯-1-酮。
Claims (5)
1.一种制备龙脑醛的方法，包括：
(a)使龙脑烯醛与式(I)的胺反应：
其中，
R1和R2独立地选自C1-C6烷基或苄基；或者
R1和R2与它们所连接的氮原子一起形成含有4-7个碳原子和无或一个选自氮和氧的其它杂原子的环；
(b)将步骤(a)获得的产物在铜催化剂和溶剂的存在下用氧进行处理以制得龙脑醛，条件是该溶剂不是氯化溶剂。
2.权利要求1的方法，其中式(I)的胺为吗啉。
3.权利要求1或2的方法，其中溶剂为极性非质子溶剂。
4.权利要求3的方法，其中溶剂选自乙腈、二甲基甲酰胺和N-甲基-吡咯烷酮。
5.权利要求1的方法，其中铜催化剂选自氯化亚铜(I)和氯化铜(II)。
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| EP06016773.1 | 2006-08-11 | ||
| EP06016773A EP1886987A1 (en) | 2006-08-11 | 2006-08-11 | Process for producing 2,2,3-trimethylcyclopent-3-enecarbaldehyde (campholytic aldehyde) |
| PCT/CH2007/000385 WO2008017184A1 (en) | 2006-08-11 | 2007-08-07 | Process for producing 2,2,3-trimethylcyclopent-3-enecarbaldehyde (campholytic aldehyde) |
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| US3661942A (en) * | 1969-09-08 | 1972-05-09 | Upjohn Co | Novel chemical process |
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| JPS59157100A (ja) * | 1983-02-25 | 1984-09-06 | Kuraray Co Ltd | １２α−置換プレグナ−１，４−ジエン−３，２０−ジオン |
| DE3939759A1 (de) * | 1989-12-01 | 1991-06-06 | Bayer Ag | Verfahren zur herstellung von benzaldehyden |
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| US7718828B2 (en) | 2010-05-18 |
| DE602007012756D1 (de) | 2011-04-07 |
| EP1886987A1 (en) | 2008-02-13 |
| JP2010500294A (ja) | 2010-01-07 |
| BRPI0716017A2 (pt) | 2013-10-08 |
| ES2360636T3 (es) | 2011-06-07 |
| EP2091903A1 (en) | 2009-08-26 |
| MX2009001381A (es) | 2009-02-13 |
| JP5122566B2 (ja) | 2013-01-16 |
| CN101500978A (zh) | 2009-08-05 |
| WO2008017184A1 (en) | 2008-02-14 |
| US20100004489A1 (en) | 2010-01-07 |
| ATE499337T1 (de) | 2011-03-15 |
| EP2091903B1 (en) | 2011-02-23 |
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