CN113061072B - Method for preparing 1-cyclopropyl naphthalene - Google Patents
Method for preparing 1-cyclopropyl naphthalene Download PDFInfo
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- CN113061072B CN113061072B CN202110339208.6A CN202110339208A CN113061072B CN 113061072 B CN113061072 B CN 113061072B CN 202110339208 A CN202110339208 A CN 202110339208A CN 113061072 B CN113061072 B CN 113061072B
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- 238000000034 method Methods 0.000 title claims abstract description 30
- VZZBXOLWBXJHEK-UHFFFAOYSA-N 1-cyclopropylnaphthalene Chemical compound C1CC1C1=CC=CC2=CC=CC=C12 VZZBXOLWBXJHEK-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 12
- 229910052751 metal Inorganic materials 0.000 claims abstract description 9
- 239000002184 metal Substances 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims description 64
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 37
- 150000001875 compounds Chemical class 0.000 claims description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 26
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- 239000003638 chemical reducing agent Substances 0.000 claims description 15
- 239000003513 alkali Substances 0.000 claims description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 12
- 238000006116 polymerization reaction Methods 0.000 claims description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 239000003112 inhibitor Substances 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007810 chemical reaction solvent Substances 0.000 claims description 8
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 8
- 230000009471 action Effects 0.000 claims description 7
- 239000012279 sodium borohydride Substances 0.000 claims description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 7
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 claims description 6
- 239000003444 phase transfer catalyst Substances 0.000 claims description 6
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N 1,4-Benzenediol Natural products OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 4
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 4
- 229950005228 bromoform Drugs 0.000 claims description 3
- ZGQURDGVBSSDNF-UHFFFAOYSA-N 1,1,2,2-tetraiodoethene Chemical compound IC(I)=C(I)I ZGQURDGVBSSDNF-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- FMWLUWPQPKEARP-UHFFFAOYSA-N bromodichloromethane Chemical compound ClC(Cl)Br FMWLUWPQPKEARP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 125000000687 hydroquinonyl group Chemical group C1(O)=C(C=C(O)C=C1)* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- 125000005489 p-toluenesulfonic acid group Chemical group 0.000 claims description 2
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 8
- 230000008901 benefit Effects 0.000 abstract description 6
- 229910000510 noble metal Inorganic materials 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 238000000746 purification Methods 0.000 abstract description 4
- 230000009467 reduction Effects 0.000 abstract description 4
- 238000006722 reduction reaction Methods 0.000 abstract description 4
- 238000007363 ring formation reaction Methods 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 2
- 238000005695 dehalogenation reaction Methods 0.000 abstract description 2
- 230000018044 dehydration Effects 0.000 abstract description 2
- 238000006297 dehydration reaction Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 229940126214 compound 3 Drugs 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 7
- 229940125782 compound 2 Drugs 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 229940125898 compound 5 Drugs 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- IGGDKDTUCAWDAN-UHFFFAOYSA-N 1-vinylnaphthalene Chemical compound C1=CC=C2C(C=C)=CC=CC2=C1 IGGDKDTUCAWDAN-UHFFFAOYSA-N 0.000 description 2
- WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 2
- BWGRDBSNKQABCB-UHFFFAOYSA-N 4,4-difluoro-N-[3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide Chemical compound CC(C)C1=NN=C(C)N1C1CC2CCC(C1)N2CCC(NC(=O)C1CCC(F)(F)CC1)C1=CC=CS1 BWGRDBSNKQABCB-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229940125907 SJ995973 Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- UYVXZUTYZGILQG-UHFFFAOYSA-N methoxyboronic acid Chemical compound COB(O)O UYVXZUTYZGILQG-UHFFFAOYSA-N 0.000 description 2
- XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- AUNNTHNQWVSPPP-UHFFFAOYSA-N cyclopropyloxyboronic acid Chemical compound OB(O)OC1CC1 AUNNTHNQWVSPPP-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/26—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only halogen atoms as hetero-atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C1/00—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon
- C07C1/20—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms
- C07C1/24—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from organic compounds containing only oxygen atoms as heteroatoms by elimination of water
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- 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
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and particularly discloses a method for preparing 1-cyclopropyl naphthalene. The method adopts 1-naphthacene as raw material, and can simply and conveniently synthesize 1-cyclopropyl naphthalene through reduction, dehydration, cyclization and reduction dehalogenation. The method has the advantages of cheap and easily obtained raw materials, no need of noble metals or dangerous organic metal reagents, low raw material cost, convenient production, environmental protection and safety, and is very suitable for industrial production. The method has the advantages of high yield of each step, less byproducts and easy purification.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for preparing 1-cyclopropyl naphthalene.
Background
1-cyclopropyl naphthalene is an important organic molecular skeleton and widely exists in chemical raw materials and pharmaceutically active molecules. At present, a method for synthesizing 1-cyclopropyl naphthalene is reported, and mainly comprises the following steps:
firstly, the catalyst is prepared by coupling reaction of cyclopropylboric acid and halogenated naphthalene under a palladium catalyst, wherein the reaction equation is as follows, and the method needs noble metal and methylboric acid, has high cost and is not beneficial to industrialized mass production;
the bis-cyclopropyl metal reagents (e.g., lithium, magnesium) and the halonaphthalenes are prepared by palladium or nickel catalyzed coupling. The method also uses noble metals and high-activity metal reagents, and is not beneficial to industrial mass production.
Thirdly, the 1-vinyl naphthalene and the dihalomethane are subjected to cyclization under the action of strong alkali tert-butyl magnesium chloride to obtain the 1-cyclopropyl naphthalene, wherein the reaction equation is as follows, and the method uses a high-activity metal reagent, so that the method is not beneficial to industrial mass production.
In summary, the existing methods use either noble metals and expensive methyl boric acid or high-activity metal reagents, which results in high production cost, complex operation and extremely high risk, and are unfavorable for industrialized mass production. Meanwhile, a great amount of metal residues and a great amount of solid wastes bring great pressure to the purification and environmental protection of the compounds.
Therefore, the development of a new method for preparing 1-cyclopropyl naphthalene, which is more suitable for industrial production, has important significance.
Disclosure of Invention
The invention solves the technical problem of providing a method for preparing 1-cyclopropyl naphthalene, and the method has the advantages of cheap and easily obtained raw materials, no need of noble metal, convenient production, environmental protection, safety and easy purification.
In order to solve the technical problems, the invention adopts the following technical scheme: a method for preparing 1-cyclopropyl naphthalene, the reaction equation is:
wherein X is selected from halogen, preferably any one of chlorine, bromine and iodine;
the preparation method comprises the following steps:
the first step: reducing the compound shown in the formula 1 by using a reducing agent 1 to obtain a compound shown in the formula 2;
and a second step of: dehydrating the compound shown in the formula 2 under the action of a catalyst and a polymerization inhibitor to obtain a compound shown in the formula 3;
and a third step of: cyclizing the compound shown in the formula 3 under the action of a cyclizing reagent and alkali to synthesize a compound shown in the formula 4;
fourth step: the compound shown in the formula 4 is reduced under the action of a reducing agent 2 and alkali to obtain a compound 1-cyclopropyl naphthalene shown in the formula 5;
wherein the reducing agent 1 is selected from any one or a mixture of a plurality of sodium borohydride, lithium aluminum hydride and diisobutyl aluminum hydride;
the catalyst is any one or the mixture of a plurality of methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid and sulfuric acid;
the polymerization inhibitor is hydroquinone and/or p-tertiary butyl phenol;
the cyclizing reagent is any one or a mixture of more of chloroform, monobromodichloromethane, bromoform and diiodoform;
the reducing agent 2 is any one or a mixture of a plurality of metals of copper, iron, zinc, lithium, sodium, potassium and aluminum;
the alkali is inorganic alkali.
As a preferred embodiment of the present invention, the reaction solvent in the first step is any one of methanol, ethanol, isopropanol, preferably methanol;
the reducing agent 1 is sodium borohydride;
the molar ratio of the compound represented by formula 1 to the reducing agent 1 is 1 (0.5 to 1), preferably 1 (0.7 to 0.9).
As a preferred embodiment of the present invention, the reaction solvent in the second step is toluene, xylene, preferably toluene;
the catalyst is p-toluenesulfonic acid;
the molar ratio of the compound shown in the formula 2 to the catalyst is (10-3): 1, preferably (5-6): 1; and/or the polymerization inhibitor is used in an amount of 0.02 to 0.03 mol percent based on the number of moles of the compound shown in the formula 2.
Further preferably, the second step of reaction is performed in a pipeline, the compound shown in the formula 2, the catalyst and the polymerization inhibitor are added into the solvent and mixed uniformly, then the mixture is pumped into the reaction pipeline, the reaction is performed when the mixture flows through the reaction pipeline, and the mixture is cooled to room temperature after flowing out of the reaction pipeline, so as to obtain the compound shown in the formula 3; the temperature of the reaction tube is 120 to 140 ℃, and more preferably 130 ℃.
In order to avoid self-polymerization of the compound represented by formula 3 at high temperature, a method of adding a polymerization inhibitor in the reaction is adopted, so that the compound 3 can exist stably in the reaction system for a short time. Meanwhile, a pipeline flow chemical synthesis method is adopted, so that the residence time of the generated compound 3 at high temperature is shortened as much as possible, the effect that the compound 3 is almost free from polymerization is achieved, and the reaction yield is improved.
As a preferred embodiment of the invention, in the third step, the base used is sodium hydroxide and/or potassium hydroxide, preferably sodium hydroxide;
the reaction solvent is toluene;
the molar ratio of the compound of formula 3 to the cyclizing reagent to the base is 1: (2-6): (4-6).
Further preferably, in the third reaction step, in order to increase the reaction yield, a phase transfer catalyst is further added to the reaction system, wherein the phase transfer catalyst is any one of 18-crown-6 ether, tetrabutylammonium fluoride, tetrabutylammonium chloride and tetrabutylammonium bromide, and the amount of the phase transfer catalyst is preferably 8 to 15% by weight of the compound represented by formula 3.
In the fourth step, as a preferred embodiment of the invention, the reducing agent 2 used in the reaction is metallic zinc powder;
the alkali is sodium hydroxide and/or potassium hydroxide, preferably sodium hydroxide;
the reaction solvent is any one of acetonitrile, propionitrile, methanol, ethanol and isopropanol;
the reaction mole ratio of the compound shown in the formula 4, the reducing agent 2 and the alkali is 1: (7-10): (14-18).
The invention also provides 1-cyclopropyl naphthalene which is prepared by adopting the method.
The invention has the following beneficial effects: the invention provides a novel method for preparing 1-cyclopropyl naphthalene, which adopts 1-naphthalene ethanone as a raw material and synthesizes 1-cyclopropyl naphthalene simply and conveniently through four steps of reduction, dehydration, cyclization and reduction dehalogenation. The method has the advantages of cheap and easily obtained raw materials, no need of noble metals or dangerous organic metal reagents, low raw material cost, convenient production, environmental protection and safety, and is very suitable for industrial production. The method has the advantages of high yield of each step and few byproducts, for example, the intermediate product 1-vinyl naphthalene is conveniently synthesized by a pipeline flow chemical mode, the defect that the compound 3 is easy to polymerize and generate side reaction is effectively avoided, the reaction yield is further improved, and the reaction product has the advantage of easy purification and has important significance for industrial production.
Detailed Description
The following describes the technical scheme of the present invention in detail by examples.
Example 1
The reaction equation of this example is:
the preparation method comprises the following steps:
(1) 1kg of sodium borohydride was added to a mixture of 5.53kg of Compound 1 and 20kg of methanol in portions, stirred for 2 hours after the addition, and water was added to quench the reaction after the completion of the HPLC detection. Then ethyl acetate and saturated ammonium chloride are used for liquid extraction, ethyl acetate is used for extracting the water phase for three times, the organic phases are combined, and the drying and spin-drying are carried out to obtain 5.53kg of compound 2, the GC purity is more than 99%, and the yield is 98.9%.
The detection data for compound 2 were: 1 H NMR(CDCl 3 ,400MHz):δ＝1.68(d,J＝6.4Hz,3H),5.68(q,J＝6.5Hz,1H),7.43-7.57(m,3H),7.68(d,J＝7.0Hz,1H),7.78(d,J＝8.2Hz,1H),7.83 7.93(m,1H),8.12(d,J＝7.9Hz,1H)。
(2) 5.53kg of Compound 2, 1kg of p-toluenesulfonic acid, 1g of hydroquinone and 80L of toluene were mixed uniformly, and then pumped into a reaction coil which had been heated to 130℃by a diaphragm pump, the reaction mixture was allowed to flow through the reaction coil, the reaction was carried out while flowing through a reaction tube, and the mixture was immediately cooled to room temperature by a condensing apparatus after flowing out from the reaction tube. The reaction solution was collected, and 20L of water was added thereto to wash out the catalyst p-toluenesulfonic acid. Then the organic phase is dried and concentrated to obtain 4.9kg of compound 3, the GC purity is more than 95%, and the yield is 98.9%.
The detection data for compound 3 were: 1 H NMR(CDCl 3 ,400MHz):δ＝8.13(d，J＝7.89，1H)，7.87-7.78(m，2H)，7.63(d，J＝7.12，1H)，7.54-7.44(m，4H)，5.80(dd，J＝17.29，J＝1.45，1H)，5.49(dd，J＝10.92，J＝1.44，1H)。
(3) 2kg of sodium hydroxide was added in portions to a mixture of 1.6kg of Compound 3, 5kg of chloroform, 0.14kg of 18-crown-6 ether and 50L of toluene at room temperature, the reaction was started after the addition was completed, and the reaction was checked to completion by HPLC. Insoluble matter was removed by filtration, and then 20L of saturated brine was added thereto, followed by stirring for 1 hour, standing and separating. The organic phase is concentrated to give 1.97kg of compound 4a with a GC purity of more than 95% and a yield of 80.0%.
The detection data for compound 4a were: 1 H NMR(CDCl 3 ,400MHz):δ＝8.27(d，J＝8.4，1H)，7.95(d，J＝8，1H)，7.88(d，J＝8，1H)，7.71-7.67(m，2H)，7.62-7.44(m，1H)，7.29(d，J＝6，1H)，3.31-3.27(m，1H)，2.20-2.07(m，2H)。
(4) 6kg of sodium hydroxide are added in portions under reflux to a mixture of 2.2kg of compound 4a, 5kg of zinc powder and 15kg of acetonitrile, after which stirring is continued until the HPLC starting material has disappeared. Cooling, dripping 10kg of acetic acid, stirring for 1 hour after dripping, filtering to remove insoluble substances, and concentrating. Adding petroleum ether and saturated saline water for liquid-separating extraction. The organic phase is dried and concentrated to obtain oily liquid. This oily liquid was distilled under reduced pressure to give 1.23kg of Compound 5 having a GC purity of more than 95% and a yield of 78.5%.
The detection data for compound 3 were: 1 H NMR(CDCl 3 ,400MHz):δ＝8.40(d,J＝8.3Hz,1H),7.80-6.90(m,6H),1.80(m,1H),1.05(m,2H),0.78(m,2H)。
example 2
The reaction equation of this example is:
the preparation method comprises the following steps:
(1) 1kg of sodium borohydride is added to a mixture of 5.53kg of compound 1 and 20kg of methanol in portions, stirred for 2 hours after the addition, quenched by water after the reaction is detected by HPLC, and extracted by adding ethyl acetate and saturated ammonium chloride in a liquid-separated manner. The aqueous phase was extracted three times with ethyl acetate, the organic phases were combined and dried to give 5.53kg of Compound 2 with a GC purity of greater than 99% and a yield of 98.9%.
(2) 5.53kg of Compound 2, 1kg of p-toluenesulfonic acid, 1g of p-tert-butylphenol and 80L of toluene were mixed uniformly, and then pumped into a reaction coil which had been heated to 130℃by a diaphragm pump, the reaction mixture was allowed to flow through the reaction coil, the reaction was carried out while flowing through a reaction tube, and the reaction tube was cooled to room temperature by a condensing apparatus immediately after flowing out of the reaction tube. The reaction solution was collected, and 20L of water was added thereto to wash out the catalyst p-toluenesulfonic acid. Then the organic phase is dried and concentrated to obtain 4.8kg of compound 3, the GC purity is more than 95%, and the yield is 96.9%.
(3) 2kg of sodium hydroxide was added in portions to a mixture of 1.6kg of Compound 3, 5kg of chloroform, 0.2kg of tetrabutylammonium chloride and 50L of toluene at room temperature, and the reaction was completed and detected by HPLC. Insoluble matter was removed by filtration, and then 20L of saturated brine was added thereto, followed by stirring for 1 hour, standing and separating. The organic phase is concentrated to give 1.86kg of compound 4a with a GC purity of greater than 95% in 75.5% yield.
(4) 6kg of sodium hydroxide are added in portions under reflux to a mixture of 2.2kg of compound 4a, 5kg of zinc powder and 15kg of ethanol, and stirring is continued after the addition is completed until the HPLC starting material has disappeared. Cooling, dripping 10kg of acetic acid, stirring for 1 hour after dripping, filtering to remove insoluble substances, and concentrating. Adding petroleum ether and saturated saline water for liquid-separating extraction. The organic phase is dried and concentrated to obtain oily liquid. This oily liquid was distilled under reduced pressure to give 1.4kg of Compound 5 having a GC purity of more than 95% and a yield of 89.4%.
Example 3
The reaction equation in this example is:
the preparation method comprises the following steps:
(1) 1kg of sodium borohydride was added to a mixture of 5.53kg of Compound 1 and 20kg of methanol in portions, stirred for 2 hours after the addition, and water was added to quench the reaction after the completion of the HPLC detection. Ethyl acetate and saturated ammonium chloride were added for liquid-phase extraction. The aqueous phase was extracted three times with ethyl acetate, the organic phases were combined and dried to give 5.53kg of Compound 2 with a GC purity of greater than 99% and a yield of 98.9%.
(2) 5.53kg of Compound 2, 1kg of p-toluenesulfonic acid, 1g of p-tert-butylphenol and 80L of toluene were mixed uniformly, and then pumped into a reaction coil which had been heated to 130℃by a diaphragm pump, the reaction mixture was allowed to flow through the reaction coil, the reaction was carried out while flowing through a reaction tube, and the reaction tube was cooled to room temperature by a condensing apparatus immediately after flowing out of the reaction tube. The reaction solution was collected, and 20L of water was added thereto to wash out the catalyst p-toluenesulfonic acid. Then the organic phase is dried and concentrated to obtain 4.8kg of compound 3, the GC purity is more than 95%, and the yield is 96.9%.
(3) 2kg of sodium hydroxide was added in portions to a mixture of 1.6kg of Compound 3, 5kg of chloroform, 0.2kg of tetrabutylammonium chloride and 50L of toluene at room temperature, and after the addition, the reaction was completed by HPLC. Insoluble matter was removed by filtration, and then 20L of saturated brine was added thereto, followed by stirring for 1 hour, standing and separating. The organic phase is concentrated to give 1.86kg of compound 4a with a GC purity of greater than 95% in 75.5% yield.
(4) 6kg of sodium hydroxide are added in portions under reflux to a mixture of 2.2kg of compound 4a, 5kg of zinc powder and 15kg of methanol, and stirring is continued after the addition is completed until the HPLC starting material has disappeared. Cooling, dripping 10kg of acetic acid, stirring for 1 hour after dripping, filtering to remove insoluble substances, and concentrating. Adding petroleum ether and saturated saline water for liquid-separating extraction. The organic phase is dried and concentrated to obtain oily liquid. This oily liquid was distilled under reduced pressure to give 1.1kg of compound 5 having a GC purity of more than 95% and a yield of 70.2%.
Example 4
The reaction equation in this example is:
synthesized by the following steps:
the synthesis of compound 2 and compound 3 was prepared as described in reference to example 1.
Synthesis of Compound 4 b: 2kg of sodium hydroxide was added in portions to a mixture of 1.6kg of Compound 3, 13.1kg of bromoform, 0.14kg of 18-crown-6 ether and 50L of toluene at room temperature, and the reaction was completed and detected by HPLC. Insoluble matter was removed by filtration, and then 20L of saturated brine was added thereto, followed by stirring for 1 hour, standing and separating. The organic phase was concentrated to give 3.49kg of compound 4b. The GC purity is more than 95 percent, and the yield is 80 percent.
Synthesis of Compound 5: 6kg of sodium hydroxide are added in portions under reflux to a mixture of 3kg of compound 4b, 5kg of zinc powder and 15kg of methanol, and stirring is continued after the addition is completed until the HPLC starting material has disappeared. Cooling, dripping 10kg of acetic acid, stirring for 1 hour after dripping, filtering to remove insoluble substances, and concentrating. Adding petroleum ether and saturated saline water for liquid-separating extraction. The organic phase is dried and concentrated to obtain oily liquid. This oily liquid was distilled under reduced pressure to give 1.15kg of Compound 5 having a GC purity of more than 95% and a yield of 73.2%.
Example 5
The reaction equation in this example is:
synthesized by the following steps:
the synthesis of compound 2 and compound 3 was prepared as described in reference to example 1.
Synthesis of Compound 4 c: 2kg of sodium hydroxide was added in portions to a mixture of 1.6kg of Compound 3, 20.4kg of diiodomethane, 0.14kg of 18-crown-6 ether and 50L of toluene, and the reaction was completed and detected by HPLC. Insoluble matter was removed by filtration, and then 20L of saturated brine was added thereto, followed by stirring for 1 hour, standing and separating. The organic phase was concentrated to give 1.86kg of compound 4c with a GC purity of greater than 95%.
Synthesis of Compound 5: 6kg of sodium hydroxide are added in portions under reflux to a mixture of 3.9kg of compound 4c, 5kg of zinc powder and 15kg of methanol, and stirring is continued after the addition is completed until the HPLC starting material has disappeared. Cooling, dripping 10kg of acetic acid, stirring for 1 hour after dripping, filtering to remove insoluble substances, and concentrating. Adding petroleum ether and saturated saline water for liquid-separating extraction. The organic phase is dried and concentrated to obtain oily liquid. This oily liquid was distilled under reduced pressure to give 1.05kg of Compound 5 having a GC purity of more than 95% and a yield of 67.0%.
The foregoing description is only illustrative of the present invention and is not intended to limit the scope of the invention, and all equivalent modifications made by the teachings of the present invention, or direct or indirect application in other related arts, are included in the scope of the present invention.
Claims (7)
1. A method for preparing 1-cyclopropyl naphthalene, characterized in that the reaction equation is:
wherein X is selected from any one of chlorine, bromine and iodine;
the preparation method comprises the following steps:
the first step: reducing the compound shown in the formula 1 by using a reducing agent 1 to obtain a compound shown in the formula 2;
and a second step of: dehydrating the compound shown in the formula 2 under the action of a catalyst and a polymerization inhibitor to obtain a compound shown in the formula 3;
and a third step of: cyclizing the compound shown in the formula 3 under the action of a cyclizing reagent and alkali to synthesize a compound shown in the formula 4; in the third reaction step, a phase transfer catalyst is also added in the reaction system, wherein the phase transfer catalyst is any one of 18-crown-6 ether, tetrabutylammonium fluoride, tetrabutylammonium chloride and tetrabutylammonium bromide;
fourth step: the compound shown in the formula 4 is reduced under the action of a reducing agent 2 and alkali to obtain a compound 1-cyclopropyl naphthalene shown in the formula 5;
wherein the reducing agent 1 is selected from any one or a mixture of a plurality of sodium borohydride, lithium aluminum hydride and diisobutyl aluminum hydride;
the catalyst is any one or the mixture of a plurality of methanesulfonic acid, trifluoromethanesulfonic acid, p-toluenesulfonic acid, benzenesulfonic acid and sulfuric acid;
the polymerization inhibitor is hydroquinone and/or p-tertiary butyl phenol;
the cyclizing reagent is any one or a mixture of more of chloroform, monobromodichloromethane, bromoform and diiodoform;
the reducing agent 2 is metal zinc powder;
in the third step, the adopted alkali is sodium hydroxide and/or potassium hydroxide;
in the fourth step, the alkali is sodium hydroxide and/or potassium hydroxide.
2. The method according to claim 1, wherein the reaction solvent in the first step is any one of methanol, ethanol, and isopropanol; and/or, the reducing agent 1 is sodium borohydride; and/or the mol ratio of the compound shown in the formula 1 to the reducing agent 1 is 1 (0.5-1).
3. The method according to claim 1 or 2, wherein the reaction solvent in the second step is toluene, xylene; and/or the catalyst is p-toluenesulfonic acid; and/or the reaction mole ratio of the compound shown in the formula 2 and the catalyst is (10-3): 1; and/or the polymerization inhibitor is used in an amount of 0.02 to 0.03 mol percent based on the number of moles of the compound shown in the formula 2.
4. The method according to claim 3, wherein the second reaction is carried out in a pipeline, the compound shown in the formula 2, the catalyst and the polymerization inhibitor are added into the solvent to be uniformly mixed, then the mixture is pumped into the reaction pipeline to react while flowing through the reaction pipeline, and the mixture is cooled to room temperature after flowing out of the reaction pipeline to obtain the compound shown in the formula 3; the temperature of the reaction pipeline is 120-140 ℃.
5. The process according to claim 4, wherein in the third step, the reaction solvent is toluene; and/or, the reaction mole ratio of the compound shown in the formula 3 to the cyclizing reagent and the alkali is 1: (2-6): (4-6).
6. The method according to claim 5, wherein the amount of the phase transfer catalyst used in the third reaction step is 8 to 15% by weight based on the compound represented by formula 3.
7. The method according to claim 5 or 6, wherein in the fourth step, the reaction solvent is any one of acetonitrile, propionitrile, methanol, ethanol, isopropanol; and/or the reaction mole ratio of the compound shown in the formula 4, the reducing agent 2 and the alkali is 1: (7-10): (14-18).
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