WO2024040754A1 - Method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane - Google Patents
Method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane Download PDFInfo
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- WO2024040754A1 WO2024040754A1 PCT/CN2022/131263 CN2022131263W WO2024040754A1 WO 2024040754 A1 WO2024040754 A1 WO 2024040754A1 CN 2022131263 W CN2022131263 W CN 2022131263W WO 2024040754 A1 WO2024040754 A1 WO 2024040754A1
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- cis
- methyl
- octadecene
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- XDBKLFODBADBED-YPKPFQOOSA-N (z)-2-methyloctadec-7-ene Chemical compound CCCCCCCCCC\C=C/CCCCC(C)C XDBKLFODBADBED-YPKPFQOOSA-N 0.000 title claims abstract description 42
- HFOFYNMWYRXIBP-MOPGFXCFSA-N 2-methyl-7S,8R-Epoxy-octadecane Chemical compound CCCCCCCCCC[C@H]1O[C@H]1CCCCC(C)C HFOFYNMWYRXIBP-MOPGFXCFSA-N 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 14
- 230000002194 synthesizing effect Effects 0.000 title abstract 2
- 150000007530 organic bases Chemical class 0.000 claims abstract description 13
- 230000009471 action Effects 0.000 claims abstract description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 56
- 238000006243 chemical reaction Methods 0.000 claims description 36
- -1 phosphonium salt compound Chemical class 0.000 claims description 29
- 239000003208 petroleum Substances 0.000 claims description 28
- 238000001308 synthesis method Methods 0.000 claims description 26
- 238000004440 column chromatography Methods 0.000 claims description 19
- 239000012141 concentrate Substances 0.000 claims description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- 239000012071 phase Substances 0.000 claims description 16
- 238000007363 ring formation reaction Methods 0.000 claims description 16
- 239000000741 silica gel Substances 0.000 claims description 16
- 229910002027 silica gel Inorganic materials 0.000 claims description 16
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 16
- 238000006467 substitution reaction Methods 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 11
- 150000004965 peroxy acids Chemical class 0.000 claims description 11
- 229940038384 octadecane Drugs 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims description 8
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 8
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 7
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 6
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical group [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 5
- 238000012805 post-processing Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 4
- 230000005526 G1 to G0 transition Effects 0.000 claims description 4
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 238000010791 quenching Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 3
- YNXURHRFIMQACJ-UHFFFAOYSA-N lithium;methanidylbenzene Chemical compound [Li+].[CH2-]C1=CC=CC=C1 YNXURHRFIMQACJ-UHFFFAOYSA-N 0.000 claims description 3
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 3
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 3
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 3
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadecene Natural products CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims 6
- 238000010189 synthetic method Methods 0.000 claims 4
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims 2
- NRUBUZBAZRTHHX-UHFFFAOYSA-N lithium;propan-2-ylazanide Chemical compound [Li+].CC(C)[NH-] NRUBUZBAZRTHHX-UHFFFAOYSA-N 0.000 claims 1
- 150000003003 phosphines Chemical class 0.000 abstract description 7
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- XDBKLFODBADBED-BUHFOSPRSA-N (e)-2-methyloctadec-7-ene Chemical compound CCCCCCCCCC\C=C\CCCCC(C)C XDBKLFODBADBED-BUHFOSPRSA-N 0.000 abstract description 3
- 238000003756 stirring Methods 0.000 description 23
- 239000000243 solution Substances 0.000 description 18
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 239000007789 gas Substances 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000721703 Lymantria dispar Species 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 150000003839 salts Chemical group 0.000 description 5
- 239000002274 desiccant Substances 0.000 description 4
- 239000000877 Sex Attractant Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012267 brine Substances 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- JKVYAKJCVCKKGL-UHFFFAOYSA-N 2-hexadecyl-2-methyloxirane Chemical compound CCCCCCCCCCCCCCCCC1(C)CO1 JKVYAKJCVCKKGL-UHFFFAOYSA-N 0.000 description 1
- HFOFYNMWYRXIBP-RBUKOAKNSA-N 2-methyl-7R,8S-Epoxy-octadecane Chemical compound CCCCCCCCCC[C@@H]1O[C@@H]1CCCCC(C)C HFOFYNMWYRXIBP-RBUKOAKNSA-N 0.000 description 1
- WQMKDHREUPHQQE-UHFFFAOYSA-N 2-methyloctadec-7-yne Chemical compound CCCCCCCCCCC#CCCCCC(C)C WQMKDHREUPHQQE-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- BYRPTKZOXNFFDB-UHFFFAOYSA-N lithium;bis(trimethylsilyl)azanide;oxolane Chemical compound [Li+].C1CCOC1.C[Si](C)(C)[N-][Si](C)(C)C BYRPTKZOXNFFDB-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- LQERIDTXQFOHKA-UHFFFAOYSA-N nonadecane Chemical compound CCCCCCCCCCCCCCCCCCC LQERIDTXQFOHKA-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
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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
- C07C1/32—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen
- C07C1/34—Preparation of hydrocarbons from one or more compounds, none of them being a hydrocarbon starting from compounds containing hetero-atoms other than or in addition to oxygen or halogen reacting phosphines with aldehydes or ketones, e.g. Wittig reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D301/00—Preparation of oxiranes
- C07D301/02—Synthesis of the oxirane ring
- C07D301/03—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds
- C07D301/14—Synthesis of the oxirane ring by oxidation of unsaturated compounds, or of mixtures of unsaturated and saturated compounds with organic peracids, or salts, anhydrides or esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/04—Compounds containing oxirane rings containing only hydrogen and carbon atoms in addition to the ring oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
Definitions
- the invention relates to the technical field of organic synthesis, and in particular to a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane.
- the racemic gypsy moth sex pheromone, cis-7,8-epoxy-2-methyloctadecane is often used. Therefore, the key intermediate cis- 2-Methyl-7-octadecene is used as raw material, and the target product cis-7,8-epoxy-2-methyloctadecane is synthesized through epoxidation reaction.
- the key intermediate cis-2-methyl-7-octadecene is usually made of 2-methyl-7-octadecyne as the raw material, and is hydrogenated in the cis form under the action of Lindler catalyst, or using a highly hindered boron reagent. Reduction is obtained (Chemistry of Natural Compounds 1983,19,593; J.Chem.Ecolo.1983,9(2),211.).
- the object of the present invention is to provide a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane.
- the synthesis method of cis-2-methyl-7-octadecene provided by the invention can avoid the generation of trans-2-methyl-7-octadecene, thereby improving the synthesis of cis-7,8-epoxy-2 -Yield and purity of methyloctadecane.
- the invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:
- the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;
- Ar is an aromatic group
- the Ar is phenyl, p-methylphenyl, p-cumylphenyl, p-tert-butylphenyl, o-methylphenyl, o-cumylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.
- the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, and hexamethyldisilamine
- the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is 1:1 to 1.2.
- the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is 1:1 to 1.2.
- the temperature of the substitution reaction is -80 ⁇ -30°C and the time is 4 ⁇ 6 hours.
- the invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:
- cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
- the peroxyacid is one or more selected from the group consisting of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.
- the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is 1:1.2-1.8.
- the temperature of the cyclization reaction is -10 to 30°C, and the time is 1 to 5 hours.
- the invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps: under the action of an organic base, an N-sulfonylhydrazone compound with a structure shown in formula a and a compound with formula b
- the phosphine salt compound with the structure shown undergoes a substitution reaction to obtain cis-2-methyl-7-octadecene.
- the invention uses N-sulfonyl hydrazone and phosphonium salt as raw materials, and under the action of organic base, can obtain cis-2-methyl-7-octadecene in one step, and can avoid trans-2-methyl-7 -Generation of octadecene.
- the yield and purity of cis-2-methyl-7-octadecene obtained by the present invention are both relatively high. Among them, the yield of cis-2-methyl-7-octadecene is 68 to 96%, and the purity is higher than 98.8%. At the same time, the raw materials used in the synthesis method of the present invention are easily available and the cost is low. It has the advantages of short synthesis route, simple operation, convenient product separation and purification, wide applicability of reaction substrates, etc., and is suitable for industrial mass production.
- the invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane.
- cis-2-methyl-7-octadecane is synthesized according to the above method, and then the peroxyacid Under the action of , cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
- cis-2-methyl-7-octadecane has higher purity
- the yield and purity of cis-7,8-epoxy-2-methyloctadecane obtained in the present invention are relatively high, among which cis-7,8-epoxy-2-methyloctadecane has higher purity.
- the yield of formula-7,8-epoxy-2-methyloctadecane is higher than 90%, and the purity is higher than 99%.
- the synthesis method provided by the invention is simple to operate, low in cost, and suitable for industrial mass production.
- Figure 1 shows the synthetic route of cis-7,8-epoxy-2-methyloctadecane
- Figure 2 is the carbon spectrum NMR spectrum of cis-7,8-epoxy-2-methyloctadecane obtained in Example 1.
- the invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:
- the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;
- Ar is an aromatic group
- the Ar is preferably phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butyl Phenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.
- the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, hexamethyldimethyl Lithium silamide, sodium hexamethyldisilamide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, isopropylmagnesium bromide and phenyl bromide
- magnesium magnesium
- the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is preferably 1:1 to 1.2, more preferably 1:1.1.
- the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is preferably 1:1 to 1.2, more preferably 1:1.1.
- the organic solvent used in the substitution reaction is preferably one of toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether and ethylene glycol dimethyl ether, or Several kinds.
- the substitution reaction is preferably carried out under a protective atmosphere, and the protective atmosphere is preferably argon.
- the preferred mixing method is: first mix the phosphonium salt compound having the structure represented by formula b with an organic base and an organic solvent, and then add the N-sulfonylhydrazone compound having the structure represented by formula a.
- the temperature of the substitution reaction is preferably -80 to -30°C, more preferably -80 to -60°C; the time is preferably 4 to 6 hours, more preferably 5 hours.
- the present invention after the substitution reaction, the present invention preferably performs post-treatment on the obtained substitution reaction liquid, and the post-treatment preferably includes the following steps:
- the organic solvent of the quenched reaction solution is removed, the remaining liquid is mixed with petroleum ether, and solid-liquid separation, washing, drying and concentration are performed in sequence.
- the obtained concentrate is purified by column chromatography to obtain cis-2-methyl-7- Pure octadecene.
- the solid-liquid separation method is preferably suction filtration; the washing detergent is preferably salt water; the drying is preferably desiccant drying, and the desiccant is preferably sodium sulfate.
- the present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.
- the stationary phase used for column chromatography purification is preferably silver nitrate-loaded 400 mesh silica gel;
- the mobile phase is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably 150: 1.
- the invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:
- cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
- cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
- the peroxyacid is preferably one or more of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.
- the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is preferably 1:1.2-1.8, more preferably 1:1.4-1.6.
- the organic solvent used in the cyclization reaction is preferably toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1,2 -One or more of dichloroethane, chloroform and methylene chloride.
- the temperature of the cyclization reaction is preferably -10 ⁇ 30°C, more preferably 0 ⁇ 10°C; the time is preferably 1 ⁇ 5h, more preferably 2 ⁇ 4h.
- the present invention preferably performs post-processing on the obtained cyclization reaction liquid, and the post-processing preferably includes the following steps:
- the detergent used for washing is preferably a sodium carbonate aqueous solution, and the number of washings is preferably 2 times.
- the drying is preferably drying with a desiccant, and the desiccant is preferably sodium sulfate.
- the present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.
- the stationary phase for column chromatography purification is preferably 200 mesh silica gel
- the mobile phase is preferably petroleum ether and ethyl acetate
- the volume ratio of petroleum ether and ethyl acetate is preferably 20:1.
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Abstract
The present invention relates to the technical field of organic synthesis, and provides a method for synthesizing cis-2-methyl-7-octadecene and cis-7,8-epoxy-2-methyloctadecane. According to the present invention, N-sulfonylhydrazone and phosphine salt are taken as raw materials, cis-2-methyl-7-octadecene can be obtained by a one-step method under the action of an organic base, and the generation of trans-2-methyl-7-octadecene can be avoided. The yield and the purity of the cis-2-methyl-7-octadecene obtained in the present invention are both high, the yield of the cis-2-methyl-7-octadecene is 68-96%, and the purity of the cis-2-methyl-7-octadecene is higher than 98.8%. Because the cis-2-methyl-7-octadecene has high purity, the yield and the purity of the cis-7,8-epoxy-2-methyloctadecane obtained in the present invention are both high, the yield of the cis-7,8-epoxy-2-methyloctadecane is higher than 90%, and the purity of the cis-7,8-epoxy-2-methyloctadecane is higher than 99%.
Description
本申请要求于2022年8月24日提交中国专利局、申请号为CN202211016165.9、发明名称为“一种顺-2-甲基-7-十八烯以及顺式-7,8-环氧-2-甲基十八烷的合成方法”的中国专利申请的优先权，其全部内容通过引用结合在本申请中。This application is required to be submitted to the China Patent Office on August 24, 2022. The application number is CN202211016165.9, and the invention name is "A cis-2-methyl-7-octadecene and cis-7,8-epoxy" -2-Methyloctadecane Synthesis Method", the entire content of which is incorporated into this application by reference.
本发明涉及有机合成技术领域，特别涉及一种顺-2-甲基-7-十八烯以及顺式-7,8-环氧-2-甲基十八烷的合成方法。The invention relates to the technical field of organic synthesis, and in particular to a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane.
1970年，Bierl等研究者从舞毒蛾雌成虫体内分离并鉴定了舞毒蛾性信息素结构为(+)-(7R,8S)-7,8-环氧-2-甲基十八烷，一直以来众多化学及生物领域研究者致力于高光学纯度的舞毒蛾性信息素合成。In 1970, Bierl and other researchers isolated and identified the structure of the gypsy moth sex pheromone from the female adults of the gypsy moth as (+)-(7R,8S)-7,8-epoxy-2-methyloctadecane. Since then, many researchers in the chemical and biological fields have devoted themselves to the synthesis of high optical purity gypsy moth sex pheromones.
在实际的舞毒蛾虫情监测和成虫诱杀中，往往采用舞毒蛾性信息素外消旋体顺-7,8-环氧-2-甲基十八烷即可，是以关键中间体顺-2-甲基-7-十八烯为原料，通过环氧化反应合成得到目标产品顺-7,8-环氧-2-甲基十八烷。In actual monitoring of the gypsy moth situation and trapping of adult insects, the racemic gypsy moth sex pheromone, cis-7,8-epoxy-2-methyloctadecane, is often used. Therefore, the key intermediate cis- 2-Methyl-7-octadecene is used as raw material, and the target product cis-7,8-epoxy-2-methyloctadecane is synthesized through epoxidation reaction.
而关键中间体顺-2-甲基-7-十八烯通常以2-甲基-7-十八碳炔为原料，在林德勒催化剂作用进行顺式氢化，或者使用高位阻硼试剂进行还原得到(Chemistry of Natural Compounds 1983,19,593；J.Chem.Ecolo.1983,9(2),211.)。The key intermediate cis-2-methyl-7-octadecene is usually made of 2-methyl-7-octadecyne as the raw material, and is hydrogenated in the cis form under the action of Lindler catalyst, or using a highly hindered boron reagent. Reduction is obtained (Chemistry of Natural Compounds 1983,19,593; J.Chem.Ecolo.1983,9(2),211.).
然而，此法在反应过程总有反-2-甲基-7-十八烯的生成，所得顺-2-甲基-7-十八烯的纯度低，使得最终产物顺式-7,8-环氧-2-甲基十八烷的收率和纯度较低。However, this method always produces trans-2-methyl-7-octadecene during the reaction process, and the purity of the obtained cis-2-methyl-7-octadecene is low, making the final product cis-7,8 -The yield and purity of epoxy-2-methyloctadecane is low.
发明内容Contents of the invention
有鉴于此，本发明目的在于提供一种顺-2-甲基-7-十八烯、顺式-7,8-环氧-2-甲基十八烷的合成方法。本发明提供的顺-2-甲基-7-十八烯的合成方法能够避免反-2-甲基-7-十八烯的生成，从而提高合成顺式-7,8-环氧-2-甲基十八烷的收率和纯度。In view of this, the object of the present invention is to provide a synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane. The synthesis method of cis-2-methyl-7-octadecene provided by the invention can avoid the generation of trans-2-methyl-7-octadecene, thereby improving the synthesis of cis-7,8-epoxy-2 -Yield and purity of methyloctadecane.
为了实现上述发明目的，本发明提供以下技术方案：In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:
本发明提供了一种顺-2-甲基-7-十八烯的合成方法，包括以下步骤：The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:
在有机碱的作用下，具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物进行取代反应，得到顺-2-甲基-7-十八烯；Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;
式a中，Ar为芳香基团；In formula a, Ar is an aromatic group;
优选的，所述Ar为苯基、对甲基苯基、对异丙基苯基、对叔丁基苯基、邻甲基苯基、邻异丙基苯基、邻叔丁基苯基、1-萘基、2-萘基、邻氯苯基、邻硝基苯基、对甲氧基苯基、邻甲氧基苯基或2,4,6-三甲基苯基。Preferably, the Ar is phenyl, p-methylphenyl, p-cumylphenyl, p-tert-butylphenyl, o-methylphenyl, o-cumylphenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.
优选的，所述有机碱为甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、正丁基锂、叔丁基锂、苯基锂、二异丙基胺基锂、六甲基二硅胺基锂、六甲基二硅胺基钠、六甲基二硅胺基钾、苄基锂、甲基溴化镁、乙基溴化镁、异丙基溴化镁和苯基溴化镁中的一种或几种。Preferably, the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, and hexamethyldisilamine Lithium hexamethyldisilamide, sodium hexamethyldisilazide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, isopropylmagnesium bromide and phenylmagnesium bromide one or several kinds.
优选的，所述具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物的摩尔比为1:1～1.2。Preferably, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is 1:1 to 1.2.
优选的，所述具有式a所示结构的N-磺酰基腙化合物与有机碱的摩尔比为1:1～1.2。Preferably, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is 1:1 to 1.2.
优选的，所述取代反应的温度为-80～-30℃，时间为4～6h。Preferably, the temperature of the substitution reaction is -80~-30°C and the time is 4~6 hours.
本发明提供了一种顺式-7,8-环氧-2-甲基十八烷的合成方法，包括以下步骤：The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:
按照上述方法合成顺-2-甲基-7-十八烯；Synthesize cis-2-methyl-7-octadecene according to the above method;
在过氧酸的作用下，顺-2-甲基-7-十八烯进行环化反应，得到顺式-7,8-环氧-2-甲基十八烷。Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
优选的，所述过氧酸为过氧甲酸、过氧乙酸、过氧苯甲酸和间氯过氧苯甲酸中的一种或几种。Preferably, the peroxyacid is one or more selected from the group consisting of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.
优选的，所述顺-2-甲基-7-十八烯与过氧酸的摩尔比为1:1.2～1.8。Preferably, the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is 1:1.2-1.8.
优选的，所述环化反应的温度为-10～30℃，时间为1～5h。Preferably, the temperature of the cyclization reaction is -10 to 30°C, and the time is 1 to 5 hours.
本发明提供了一种顺-2-甲基-7-十八烯的合成方法，包括以下步骤：在有机碱的作用下，具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物进行取代反应，得到顺-2-甲基-7-十八烯。本发明以N-磺酰基腙和膦盐作为原料，在有机碱的作用下，一步法即可得到顺-2-甲基-7-十八烯，且能避免反-2-甲基-7-十八烯的生成。本发明所得顺-2-甲基-7-十八烯的收率和纯度均较高，其中，顺-2-甲基-7-十八烯的收率为68～96％，纯度高于98.8％。同时，本发明合成方法所用原料易得，成本低廉，具有合成路线短、操作简单、产品分离提纯方便、反应底物普适性广等优点，适合工业化批量生产。The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps: under the action of an organic base, an N-sulfonylhydrazone compound with a structure shown in formula a and a compound with formula b The phosphine salt compound with the structure shown undergoes a substitution reaction to obtain cis-2-methyl-7-octadecene. The invention uses N-sulfonyl hydrazone and phosphonium salt as raw materials, and under the action of organic base, can obtain cis-2-methyl-7-octadecene in one step, and can avoid trans-2-methyl-7 -Generation of octadecene. The yield and purity of cis-2-methyl-7-octadecene obtained by the present invention are both relatively high. Among them, the yield of cis-2-methyl-7-octadecene is 68 to 96%, and the purity is higher than 98.8%. At the same time, the raw materials used in the synthesis method of the present invention are easily available and the cost is low. It has the advantages of short synthesis route, simple operation, convenient product separation and purification, wide applicability of reaction substrates, etc., and is suitable for industrial mass production.
本发明提供了一种顺式-7,8-环氧-2-甲基十八烷的合成方法，先按照上述方法合成顺-2-甲基-7-十八烯，然后在过氧酸的作用下，顺-2-甲基-7-十八烯进行环化反应，得到顺式-7,8-环氧-2-甲基十八烷。由于顺-2-甲基-7-十八烯具有较高的纯度，本发明所得顺式-7,8-环氧-2-甲基十八烷的收率和纯度均较高，其中顺式-7,8-环氧-2-甲基十八烷的收率高于90％，纯度高于99％。同时，本发明提供的合成方法操作简单，成本低廉，适合工业化批量生产。The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane. First, cis-2-methyl-7-octadecane is synthesized according to the above method, and then the peroxyacid Under the action of , cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane. Since cis-2-methyl-7-octadecane has higher purity, the yield and purity of cis-7,8-epoxy-2-methyloctadecane obtained in the present invention are relatively high, among which cis-7,8-epoxy-2-methyloctadecane has higher purity. The yield of formula-7,8-epoxy-2-methyloctadecane is higher than 90%, and the purity is higher than 99%. At the same time, the synthesis method provided by the invention is simple to operate, low in cost, and suitable for industrial mass production.
图1为顺式-7,8-环氧-2-甲基十八烷的合成路线；Figure 1 shows the synthetic route of cis-7,8-epoxy-2-methyloctadecane;
图2为实施例1所得顺式-7,8-环氧-2-甲基十八烷碳谱核磁图谱。Figure 2 is the carbon spectrum NMR spectrum of cis-7,8-epoxy-2-methyloctadecane obtained in Example 1.
本发明提供了一种顺-2-甲基-7-十八烯的合成方法，包括以下步骤：The invention provides a synthesis method of cis-2-methyl-7-octadecene, which includes the following steps:
在有机碱的作用下，具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物进行取代反应，得到顺-2-甲基-7-十八烯；Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;
式a中，Ar为芳香基团；In formula a, Ar is an aromatic group;
在本发明中，所述Ar优选为苯基、对甲基苯基、对异丙基苯基、对叔丁基苯基、邻甲基苯基、邻异丙基苯基、邻叔丁基苯基、1-萘基、2-萘基、邻氯苯基、邻硝基苯基、对甲氧基苯基、邻甲氧基苯基或2,4,6-三甲基苯基。In the present invention, the Ar is preferably phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl, o-tert-butyl Phenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4,6-trimethylphenyl.
在本发明中，所述有机碱为甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、正丁基锂、叔丁基锂、苯基锂、二异丙基胺基锂、六甲基二硅胺基锂、六甲基二硅胺基钠、六甲基二硅胺基钾、苄基锂、甲基溴化镁、乙基溴化镁、异丙基溴化镁和苯基溴化镁中的一种或几种。In the present invention, the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, lithium diisopropylamide, hexamethyldimethyl Lithium silamide, sodium hexamethyldisilamide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, isopropylmagnesium bromide and phenyl bromide One or more types of magnesium.
在本发明中，所述具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物的摩尔比优选为1:1～1.2，更优选为1:1.1。In the present invention, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is preferably 1:1 to 1.2, more preferably 1:1.1.
在本发明中，所述具有式a所示结构的N-磺酰基腙化合物与有机碱的摩尔比优选为1:1～1.2，更优选为1:1.1。In the present invention, the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a to the organic base is preferably 1:1 to 1.2, more preferably 1:1.1.
在本发明中，所述取代反应使用的有机溶剂优选为甲苯、三氟甲基苯、氟苯、四氢呋喃、甲基四氢呋喃、甲基叔丁基醚和乙二醇二甲醚中的一种或几种。在本发明中，所述取代反应优选在保护气氛下进行，所述保护气氛优选为氩气。In the present invention, the organic solvent used in the substitution reaction is preferably one of toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether and ethylene glycol dimethyl ether, or Several kinds. In the present invention, the substitution reaction is preferably carried out under a protective atmosphere, and the protective atmosphere is preferably argon.
在本发明中，所述混合的方式优选为：先将具有式b所示结构的膦盐化合物与有机碱、有机溶剂混合，再加入具有式a所示结构的N-磺酰基腙化合物。In the present invention, the preferred mixing method is: first mix the phosphonium salt compound having the structure represented by formula b with an organic base and an organic solvent, and then add the N-sulfonylhydrazone compound having the structure represented by formula a.
在本发明中，所述取代反应的温度优选为-80～-30℃，更优选为-80～-60℃；时间优选为4～6h，更优选为5h。In the present invention, the temperature of the substitution reaction is preferably -80 to -30°C, more preferably -80 to -60°C; the time is preferably 4 to 6 hours, more preferably 5 hours.
在本发明中，所述取代反应后，本发明优选对所得取代反应液进行后处理，所述后处理优选包括以下步骤：In the present invention, after the substitution reaction, the present invention preferably performs post-treatment on the obtained substitution reaction liquid, and the post-treatment preferably includes the following steps:
将所述取代反应液与水混合，淬灭反应，得到淬灭反应液；Mix the substitution reaction liquid with water to quench the reaction to obtain a quenched reaction liquid;
去除所述淬灭反应液的有机溶剂，对剩余液体与石油醚混合，依次进行固液分离、洗涤、干燥和浓缩，所得浓缩物进行柱层析提纯，得到顺-2-甲基-7-十八烯纯品。The organic solvent of the quenched reaction solution is removed, the remaining liquid is mixed with petroleum ether, and solid-liquid separation, washing, drying and concentration are performed in sequence. The obtained concentrate is purified by column chromatography to obtain cis-2-methyl-7- Pure octadecene.
在本发明中，所述固液分离的方式优选为抽滤；所述洗涤用洗涤剂优选为食盐水；所述干燥优选为干燥剂干燥，所述干燥剂优选为硫酸钠。本发明对所述浓缩的方式无特殊要求，使用本领域技术人员熟知的浓缩方式即可。In the present invention, the solid-liquid separation method is preferably suction filtration; the washing detergent is preferably salt water; the drying is preferably desiccant drying, and the desiccant is preferably sodium sulfate. The present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.
在本发明中，所述柱层析提纯使用的固定相优选为负载硝酸银400目硅胶；流动相优选为石油醚和乙酸乙酯，所述石油醚和乙酸乙酯的体积比优选为150：1。In the present invention, the stationary phase used for column chromatography purification is preferably silver nitrate-loaded 400 mesh silica gel; the mobile phase is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably 150: 1.
本发明提供了一种顺式-7,8-环氧-2-甲基十八烷的合成方法，包括以下步骤：The invention provides a synthesis method of cis-7,8-epoxy-2-methyloctadecane, which includes the following steps:
按照上述方法合成顺-2-甲基-7-十八烯；Synthesize cis-2-methyl-7-octadecene according to the above method;
在过氧酸的作用下，顺-2-甲基-7-十八烯进行环化反应，得到顺式-7,8-环氧-2-甲基十八烷。Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
在本发明中，所述顺-2-甲基-7-十八烯的合成方法与上文相同，在此不再赘述。In the present invention, the synthesis method of cis-2-methyl-7-octadecene is the same as above and will not be described again.
本发明在过氧酸的作用下，顺-2-甲基-7-十八烯进行环化反应，得到顺式-7,8-环氧-2-甲基十八烷。In the present invention, under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
在本发明中，所述过氧酸优选为过氧甲酸、过氧乙酸、过氧苯甲酸和间氯过氧苯甲酸中的一种或几种。In the present invention, the peroxyacid is preferably one or more of peroxyformic acid, peracetic acid, perbenzoic acid and m-chloroperoxybenzoic acid.
在本发明中，所述顺-2-甲基-7-十八烯与过氧酸的摩尔比优选为1:1.2～1.8，更优选为1:1.4～1.6。In the present invention, the molar ratio of cis-2-methyl-7-octadecene and peroxyacid is preferably 1:1.2-1.8, more preferably 1:1.4-1.6.
在本发明中，所述环化反应使用的有机溶剂优选为甲苯、三氟甲基苯、氟苯、四氢呋喃、甲基四氢呋喃、甲基叔丁基醚、乙二醇二甲醚、1,2-二氯乙烷、氯仿和二氯甲烷中的一种或几种。In the present invention, the organic solvent used in the cyclization reaction is preferably toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1,2 -One or more of dichloroethane, chloroform and methylene chloride.
在本发明中，所述环化反应的温度优选为-10～30℃，更优选为0～10℃；时间优选为1～5h，更优选为2～4h。In the present invention, the temperature of the cyclization reaction is preferably -10~30°C, more preferably 0~10°C; the time is preferably 1~5h, more preferably 2~4h.
所述环化反应后，本发明优选对所得环化反应液进行后处理，所述后 处理优选包括以下步骤：After the cyclization reaction, the present invention preferably performs post-processing on the obtained cyclization reaction liquid, and the post-processing preferably includes the following steps:
向所述环化反应液中加入饱和硫代硫酸钠溶液淬灭反应，得到淬灭反应液；Add saturated sodium thiosulfate solution to the cyclization reaction solution to quench the reaction to obtain a quenched reaction solution;
对所述淬灭反应液进行分液，得到水相和有机相；Separate the quenched reaction solution to obtain an aqueous phase and an organic phase;
对所述有机相依次进行洗涤、干燥、浓缩和柱层析提纯，得到顺式-7,8-环氧-2-甲基十八烷纯品。The organic phase was washed, dried, concentrated and purified by column chromatography in sequence to obtain pure cis-7,8-epoxy-2-methyloctadecane.
在本发明中，所述洗涤所用的洗涤剂优选为碳酸钠水溶液，所述洗涤的次数优选为2次。在本发明中，所述干燥优选为干燥剂干燥，所述干燥剂优选为硫酸钠。本发明对所述浓缩的方式没有特殊的要求，使用本领域技术人员熟知的浓缩方式即可。In the present invention, the detergent used for washing is preferably a sodium carbonate aqueous solution, and the number of washings is preferably 2 times. In the present invention, the drying is preferably drying with a desiccant, and the desiccant is preferably sodium sulfate. The present invention has no special requirements for the concentration method, and any concentration method well known to those skilled in the art can be used.
在本发明中，所述柱层析提纯的固定相优选为200目硅胶，流动相优选为石油醚和乙酸乙酯，所述石油醚和乙酸乙酯的体积比优选为20:1。In the present invention, the stationary phase for column chromatography purification is preferably 200 mesh silica gel, the mobile phase is preferably petroleum ether and ethyl acetate, and the volume ratio of petroleum ether and ethyl acetate is preferably 20:1.
在本发明中，所述顺式-7,8-环氧-2-甲基十八烷的合成路线如图1所示。In the present invention, the synthetic route of cis-7,8-epoxy-2-methyloctadecane is shown in Figure 1.
下面结合实施例对本发明提供的一种顺-2-甲基-7-十八烯以及顺式-7,8-环氧-2-甲基十八烷的合成方法进行详细的说明，但是不能把它们理解为对本发明保护范围的限定。The synthesis method of cis-2-methyl-7-octadecane and cis-7,8-epoxy-2-methyloctadecane provided by the present invention will be described in detail below in conjunction with the examples. They should be understood as limitations on the scope of protection of the present invention.
实施例1Example 1
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和四氢呋喃(80mL)，冷却至-80℃，慢慢注入正丁基锂-正己烷溶液(8mL,1.5M)，搅拌1小时；加入N-苯磺酰基腙(3.3g,10mmol)，继续在-80℃搅拌反应4小时，然后自然升温至室温反应2小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯2.3g(收率86％，气相纯度98.6％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ;Add N-phenylsulfonylhydrazone (3.3g, 10mmol), continue to stir and react at -80°C for 4 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, concentrate to remove the solvent, and add petroleum ether (80 mL) was stirred for 30 minutes, suction filtered, the filtrate was washed with brine, dried over sodium sulfate, concentrated, and the residue was purified by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2 -Methyl-7-octadecene 2.3g (yield 86%, gas phase purity 98.6%).
1H NMR(400MHz,CDCl
3):δ0.76-1.02(m,9H),1.14-1.61(m,23H),1.89-2.16(m,4H),5.38(m,2H)。
1 H NMR (400MHz, CDCl 3 ): δ0.76-1.02(m,9H), 1.14-1.61(m,23H), 1.89-2.16(m,4H), 5.38(m,2H).
把顺-2-甲基-7-十八烯(2.3g,8.6mmol)溶解于二氯甲烷(60mL)，冷却至-5℃，分5批加入间氯过氧苯甲酸(3.2g,15.5mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机 相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺式-7,8-环氧-2-甲基十八烷2.24g(收率92％，气相纯度99.1％)。Dissolve cis-2-methyl-7-octadecene (2.3g, 8.6mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (3.2g, 15.5 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 2.24g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 92%, gas phase purity 99.1%).
1H NMR(400MHz,CDCl
3):δ0.86-0.92(m,9H),1.14-1.59(m,27H),2.85-2.96(m,2H)；
13C NMR(100MHz,CDCl
3):δ14.1,22.58,22.67,22.69,26.60,26.86,27.32,27.83,27.87,27.89，29.32,29.56,29.59,31.90,38.91,57.17；HRMS(ESI)calcd for C19H38NaO
+[M+Na
+]305.2820,found305.2825。
1 H NMR (400MHz, CDCl 3 ): δ0.86-0.92 (m, 9H), 1.14-1.59 (m, 27H), 2.85-2.96 (m, 2H); 13 C NMR (100MHz, CDCl 3 ): δ14 .1,22.58,22.67,22.69,26.60,26.86,27.32,27.83,27.87,27.89,29.32,29.56,29.59,31.90,38.91,57.17; HRMS(ESI)calcd for C19H38NaO + [M+Na + ]305.28 20,found305 .2825.
所得顺式-7,8-环氧-2-甲基十八烷碳谱核磁图谱如图2所示。The carbon NMR spectrum of the obtained cis-7,8-epoxy-2-methyloctadecane is shown in Figure 2.
实施例2Example 2
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和甲基四氢呋喃(80mL)，冷却至-60℃，慢慢注入二异丙基胺基锂溶液(6mL,2M)，搅拌0.5小时；加入N-2-萘磺酰基腙(3.8g,10mmol)，继续在-60℃搅拌反应5小时，然后自然升温至室温反应2小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯1.9g(收率71％，气相纯度98.6％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and methyltetrahydrofuran (80mL) into the reaction bottle, cool to -60°C, slowly inject lithium diisopropylamide solution (6mL, 2M), and stir for 0.5 hours; add N-2-naphthylsulfonylhydrazone (3.8g, 10mmol), continue to stir and react at -60°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove the solvent. Add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2-methyl-7-octadecene 1.9g (yield 71%, gas phase purity 98.6%).
把顺-2-甲基-7-十八烯(1.9g,7.1mmol)溶解于二氯甲烷(60mL)，冷却至-5℃，分5批加入间氯过氧苯甲酸(2.6g,12.8mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺-7,8-环氧-2-甲基十八烷1.83g(收 率91％，气相纯度99.2％)，产物的
1HNMR、
13C NMR和HRMS检测数据和实施例1一致。
Dissolve cis-2-methyl-7-octadecene (1.9g, 7.1mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (2.6g, 12.8 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 1.83g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 91%, gas phase purity 99.2%), 1 of the product The HNMR, 13 C NMR and HRMS detection data are consistent with Example 1.
实施例3Example 3
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和四氢呋喃(80mL)，冷却至-70℃，慢慢注入六甲基二硅胺基锂四氢呋喃溶液(10mL,1.5M)，搅拌1小时；加入N-对叔丁基苯磺酰基腙(3.8g,10mmol)，继续在-70℃搅拌反应5小时，然后自然升温至室温反应2小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯2.0g(收率75％，气相纯度99.5％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) into the reaction bottle, cool to -70°C, slowly inject lithium hexamethyldisilazide tetrahydrofuran solution (10mL, 1.5M), and stir 1 hour; add N-p-tert-butylbenzenesulfonylhydrazone (3.8g, 10mmol), continue to stir and react at -70°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate Remove the solvent, add petroleum ether (80 mL) and stir for 30 minutes, filter with suction, wash the filtrate with brine, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate = 150: 1) Obtain 2.0 g of cis-2-methyl-7-octadecene (yield 75%, gas phase purity 99.5%).
把顺-2-甲基-7-十八烯(2.0g,7.5mmol)溶解于1,2-二氯乙烷(100mL)，冷却至0℃，分5批加入间氯过氧苯甲酸(3.1g,15mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺-7,8-环氧-2-甲基十八烷2.1g(收率96％，气相纯度99.8％)，产物的
1HNMR、
13C NMR和HRMS检测数据和实施例1一致。
Dissolve cis-2-methyl-7-octadecene (2.0g, 7.5mmol) in 1,2-dichloroethane (100mL), cool to 0°C, and add m-chloroperoxybenzoic acid ( 3.1g, 15mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and column the residue Chromatography purification (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) gave cis-7,8-epoxy-2-methyloctadecane 2.1g (yield 96%, gas phase purity 99.8%), The 1 HNMR, 13 C NMR and HRMS detection data of the product are consistent with Example 1.
实施例4Example 4
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和四氢呋喃(80mL)，冷却至-80℃，慢慢注入正丁基锂-正己烷溶液(8mL,1.5M)，搅拌1小时；加入N-2,4,6-三甲基苯磺酰基腙(3.7g,10mmol)，继续在-80℃搅拌反应6小时，然后自然升温至室温反应4小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯1.82g(收率68％，气相纯度98.8％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ; Add N-2,4,6-trimethylbenzenesulfonylhydrazone (3.7g, 10mmol), continue to stir and react at -80°C for 6 hours, then naturally warm to room temperature and react for 4 hours; add water (5mL) dropwise to extract. Reaction, concentrate to remove the solvent, add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate =150:1) to obtain 1.82g of cis-2-methyl-7-octadecene (yield 68%, gas phase purity 98.8%).
把顺-2-甲基-7-十八烯(1.82g,6.8mmol)溶解于氯仿(50mL)，冷却至0℃，分5批加入间氯过氧苯甲酸(2.22g,10.9mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺-7,8-环氧-2-甲基十八烷1.81g(收率94％，气相纯度99.5％)，产物的
1HNMR、
13C NMR和HRMS检测数据和实施例1一致。
Dissolve cis-2-methyl-7-octadecene (1.82g, 6.8mmol) in chloroform (50mL), cool to 0°C, and add m-chloroperoxybenzoic acid (2.22g, 10.9mmol, 85 % content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and the residue will be purified by column chromatography (200 mesh) Silica gel, petroleum ether: ethyl acetate = 20:1) to obtain 1.81g of cis-7,8-epoxy-2-methyloctadecane (yield 94%, gas phase purity 99.5%), 1 HNMR of the product, 13 C NMR and HRMS detection data are consistent with Example 1.
实施例5Example 5
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和甲基四氢呋喃(80mL)，冷却至-80℃，慢慢注入正丁基锂-正己烷溶液(8mL,1.5M)，搅拌1小时；加入N-2-氯苯磺酰基腙(3.6g,10mmol)，继续在-80℃搅拌反应5小时，然后自然升温至室温反应2小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石 油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯2.56g(收率96％，气相纯度99.6％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and methyltetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir 1 hour; add N-2-chlorobenzenesulfonylhydrazone (3.6g, 10mmol), continue to stir and react at -80°C for 5 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove Solvent, add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (loaded silver nitrate 400 mesh silica gel, petroleum ether: ethyl acetate = 150:1 ) to obtain 2.56 g of cis-2-methyl-7-octadecene (yield 96%, gas phase purity 99.6%).
把顺-2-甲基-7-十八烯(2.56g,9.6mmol)溶解于氯仿(100mL)，冷却至-5℃，分10批加入间氯过氧苯甲酸(2.93g,14.4mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺-7,8-环氧-2-甲基十八烷2.58g(收率95％，气相纯度99.4％)，产物的
1HNMR、
13C NMR和HRMS检测数据和实施例1一致。
Dissolve cis-2-methyl-7-octadecene (2.56g, 9.6mmol) in chloroform (100mL), cool to -5°C, and add m-chloroperoxybenzoic acid (2.93g, 14.4mmol, in 10 batches). 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and the residue will be purified by column chromatography (200 silica gel, petroleum ether: ethyl acetate = 20:1) to obtain cis-7,8-epoxy-2-methyloctadecane 2.58g (yield 95%, gas phase purity 99.4%), 1 HNMR of the product, The 13 C NMR and HRMS detection data are consistent with Example 1.
实施例6Example 6
氩气保护下，反应瓶中加入膦盐(5.5g,12mmol)和四氢呋喃(80mL)，冷却至-80℃，慢慢注入正丁基锂-正己烷溶液(8mL,1.5M)，搅拌1小时；加入N-对甲基苯磺酰基腙(3.4g,10mmol)，继续在-80℃搅拌反应4小时，然后自然升温至室温反应2小时；滴加水(5mL)萃灭反应，浓缩除去溶剂，加入石油醚(80mL)搅拌30分钟，抽滤，滤液食盐水洗涤，硫酸钠干燥，浓缩，剩余物柱层析提纯(负载硝酸银400目硅胶，石油醚：乙酸乙酯＝150:1)得到顺-2-甲基-7-十八烯2.19g(收率82％，气相纯度98.9％)。Under argon protection, add phosphine salt (5.5g, 12mmol) and tetrahydrofuran (80mL) to the reaction bottle, cool to -80°C, slowly inject n-butyllithium-n-hexane solution (8mL, 1.5M), and stir for 1 hour. ; Add N-p-toluenesulfonylhydrazone (3.4g, 10mmol), continue to stir and react at -80°C for 4 hours, then naturally warm to room temperature and react for 2 hours; add water (5mL) dropwise to extract the reaction, and concentrate to remove the solvent. Add petroleum ether (80 mL) and stir for 30 minutes, suction filtrate, wash the filtrate with salt water, dry over sodium sulfate, concentrate, and purify the residue by column chromatography (400 mesh silica gel loaded with silver nitrate, petroleum ether: ethyl acetate = 150:1) to obtain cis-2-methyl-7-octadecene 2.19g (yield 82%, gas phase purity 98.9%).
把顺-2-甲基-7-十八烯(2.19g,8.2mmol)溶解于二氯甲烷(60mL)，冷却至-5℃，分5批加入间氯过氧苯甲酸(3.0g,14.8mmol,85％含量)；搅拌反应2小时，加入饱和硫代硫酸钠溶液(10mL)萃灭反应，分液，有机相碳酸钠水溶液洗涤2次，硫酸钠干燥，浓缩，剩余物柱层析提纯(200目硅胶，石油醚：乙酸乙酯＝20:1)得到顺-7,8-环氧-2-甲基十八烷2.21g(收率95％，气相纯度99.6％)，产物的
1HNMR、
13C NMR和HRMS检测数据和实施例1一致。
Dissolve cis-2-methyl-7-octadecene (2.19g, 8.2mmol) in dichloromethane (60mL), cool to -5°C, and add m-chloroperoxybenzoic acid (3.0g, 14.8 mmol, 85% content); stir the reaction for 2 hours, add saturated sodium thiosulfate solution (10mL) to extract the reaction, separate the liquids, wash the organic phase with sodium carbonate aqueous solution twice, dry with sodium sulfate, concentrate, and purify the residue by column chromatography (200 mesh silica gel, petroleum ether: ethyl acetate = 20:1) 2.21g of cis-7,8-epoxy-2-methyloctadecane was obtained (yield 95%, gas phase purity 99.6%), 1 of the product The HNMR, 13 C NMR and HRMS detection data are consistent with Example 1.
以上所述仅是本发明的优选实施方式，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。The above are only preferred embodiments of the present invention. It should be noted that those skilled in the art can make several improvements and modifications without departing from the principles of the present invention. These improvements and modifications can also be made. should be regarded as the protection scope of the present invention.
Claims (16)
- 一种顺-2-甲基-7-十八烯的合成方法，包括以下步骤：A synthetic method of cis-2-methyl-7-octadecene, including the following steps:在有机碱的作用下，具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物进行取代反应，得到顺-2-甲基-7-十八烯；Under the action of an organic base, the N-sulfonylhydrazone compound with the structure shown in formula a and the phosphonium salt compound with the structure shown in formula b undergo a substitution reaction to obtain cis-2-methyl-7-octadecene;
式a中，Ar为芳香基团；In formula a, Ar is an aromatic group;
- 根据权利要求1所述的合成方法，其特征在于，所述Ar为苯基、对甲基苯基、对异丙基苯基、对叔丁基苯基、邻甲基苯基、邻异丙基苯基、邻叔丁基苯基、1-萘基、2-萘基、邻氯苯基、邻硝基苯基、对甲氧基苯基、邻甲氧基苯基或2,4,6-三甲基苯基。The synthesis method according to claim 1, wherein Ar is phenyl, p-methylphenyl, p-isopropylphenyl, p-tert-butylphenyl, o-methylphenyl, o-isopropylphenyl phenyl, o-tert-butylphenyl, 1-naphthyl, 2-naphthyl, o-chlorophenyl, o-nitrophenyl, p-methoxyphenyl, o-methoxyphenyl or 2,4, 6-Trimethylphenyl.
- 根据权利要求1或2所述的合成方法，其特征在于，所述有机碱为甲醇钠、乙醇钠、乙醇钾、叔丁醇钾、正丁基锂、叔丁基锂、苯基锂、二异丙基胺基锂、六甲基二硅胺基锂、六甲基二硅胺基钠、六甲基二硅胺基钾、苄基锂、甲基溴化镁、乙基溴化镁、异丙基溴化镁和苯基溴化镁中的一种或几种。The synthesis method according to claim 1 or 2, characterized in that the organic base is sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, n-butyllithium, tert-butyllithium, phenyllithium, dimethoxide, Lithium isopropylamide, lithium hexamethyldisilamide, sodium hexamethyldisilamide, potassium hexamethyldisilamide, benzyllithium, methylmagnesium bromide, ethylmagnesium bromide, One or more of isopropyl magnesium bromide and phenyl magnesium bromide.
- 根据权利要求1所述的合成方法，其特征在于，所述具有式a所示结构的N-磺酰基腙化合物与具有式b所示结构的膦盐化合物的摩尔比为1:1～1.2。The synthesis method according to claim 1, characterized in that the molar ratio of the N-sulfonylhydrazone compound having the structure represented by formula a and the phosphonium salt compound having the structure represented by formula b is 1:1 to 1.2.
- 根据权利要求1或4所述的合成方法，其特征在于，所述具有式a所示结构的N-磺酰基腙化合物与有机碱的摩尔比为1:1～1.2。The synthesis method according to claim 1 or 4, characterized in that the molar ratio of the N-sulfonylhydrazone compound having the structure shown in formula a to the organic base is 1:1 to 1.2.
- 根据权利要求1所述的合成方法，其特征在于，所述取代反应使用的有机溶剂为甲苯、三氟甲基苯、氟苯、四氢呋喃、甲基四氢呋喃、甲基叔丁基醚和乙二醇二甲醚中的一种或几种。The synthetic method according to claim 1, characterized in that the organic solvent used in the substitution reaction is toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether and ethylene glycol One or more of dimethyl ether.
- 根据权利要求1或4所述的合成方法，其特征在于，所述取代反 应的温度为-80～-30℃，时间为4～6h。The synthesis method according to claim 1 or 4, characterized in that the temperature of the substitution reaction is -80~-30°C and the time is 4~6h.
- 根据权利要求1所述的合成方法，其特征在于，所述取代反应后，对所得取代反应液进行后处理，所述后处理包括以下步骤：The synthesis method according to claim 1, characterized in that, after the substitution reaction, the obtained substitution reaction liquid is subjected to post-processing, and the post-processing includes the following steps:将所述取代反应液与水混合，淬灭反应，得到淬灭反应液；Mix the substitution reaction liquid with water to quench the reaction to obtain a quenched reaction liquid;去除所述淬灭反应液的有机溶剂，对剩余液体与石油醚混合，依次进行固液分离、洗涤、干燥和浓缩，所得浓缩物进行柱层析提纯，得到顺-2-甲基-7-十八烯纯品。The organic solvent of the quenched reaction solution is removed, the remaining liquid is mixed with petroleum ether, and solid-liquid separation, washing, drying and concentration are performed in sequence. The obtained concentrate is purified by column chromatography to obtain cis-2-methyl-7- Pure octadecene.
- 根据权利要求8所述的合成方法，其特征在于，所述柱层析提纯使用的固定相为负载硝酸银400目硅胶；流动相为石油醚和乙酸乙酯，所述石油醚和乙酸乙酯的体积比为150：1。The synthesis method according to claim 8, wherein the stationary phase used for column chromatography purification is silver nitrate-loaded 400 mesh silica gel; the mobile phase is petroleum ether and ethyl acetate, and the petroleum ether and ethyl acetate are The volume ratio is 150:1.
- 一种顺式-7,8-环氧-2-甲基十八烷的合成方法，包括以下步骤：A synthesis method of cis-7,8-epoxy-2-methyloctadecane, including the following steps:按照权利要求1～9任意一项所述方法合成顺-2-甲基-7-十八烯；Synthesize cis-2-methyl-7-octadecene according to the method described in any one of claims 1 to 9;在过氧酸的作用下，顺-2-甲基-7-十八烯进行环化反应，得到顺式-7,8-环氧-2-甲基十八烷。Under the action of peroxyacid, cis-2-methyl-7-octadecane undergoes a cyclization reaction to obtain cis-7,8-epoxy-2-methyloctadecane.
- 根据权利要求10所述的合成方法，其特征在于，所述过氧酸为过氧甲酸、过氧乙酸、过氧苯甲酸和间氯过氧苯甲酸中的一种或几种。The synthesis method according to claim 10, wherein the peroxyacid is one or more of peroxyformic acid, peracetic acid, perbenzoic acid and meta-chloroperoxybenzoic acid.
- 根据权利要求10所述的合成方法，其特征在于，所述顺-2-甲基-7-十八烯与过氧酸的摩尔比为1:1.2～1.8。The synthesis method according to claim 10, characterized in that the molar ratio of the cis-2-methyl-7-octadecene and peroxyacid is 1:1.2~1.8.
- 根据权利要求10所述的合成方法，其特征在于，所述环化反应使用的有机溶剂为甲苯、三氟甲基苯、氟苯、四氢呋喃、甲基四氢呋喃、甲基叔丁基醚、乙二醇二甲醚、1,2-二氯乙烷、氯仿和二氯甲烷中的一种或几种。The synthetic method according to claim 10, characterized in that the organic solvent used in the cyclization reaction is toluene, trifluoromethylbenzene, fluorobenzene, tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, ethylene glycol One or more of glycol dimethyl ether, 1,2-dichloroethane, chloroform and methylene chloride.
- 根据权利要求10或12所述的合成方法，其特征在于，所述环化反应的温度为-10～30℃，时间为1～5h。The synthesis method according to claim 10 or 12, characterized in that the temperature of the cyclization reaction is -10~30°C and the time is 1~5h.
- 根据权利要求10所述的合成方法，其特征在于，所述环化反应后，对所得环化反应液进行后处理，所述后处理包括以下步骤：The synthesis method according to claim 10, characterized in that, after the cyclization reaction, the obtained cyclization reaction liquid is post-processed, and the post-processing includes the following steps:向所述环化反应液中加入饱和硫代硫酸钠溶液淬灭反应，得到淬灭反应液；Add saturated sodium thiosulfate solution to the cyclization reaction solution to quench the reaction to obtain a quenched reaction solution;对所述淬灭反应液进行分液，得到水相和有机相；Separate the quenched reaction solution to obtain an aqueous phase and an organic phase;对所述有机相依次进行洗涤、干燥、浓缩和柱层析提纯，得到顺式-7,8- 环氧-2-甲基十八烷纯品。The organic phase was washed, dried, concentrated and purified by column chromatography in sequence to obtain pure cis-7,8-epoxy-2-methyloctadecane.
- 根据权利要求15所述的合成方法，其特征在于，所述柱层析提纯的固定相为200目硅胶，流动相为石油醚和乙酸乙酯，所述石油醚和乙酸乙酯的体积比为20:1。The synthetic method according to claim 15, characterized in that the stationary phase purified by column chromatography is 200 mesh silica gel, the mobile phase is petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether and ethyl acetate is 20:1.
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| DE2758882A1 (en) * | 1977-12-30 | 1979-07-05 | Basf Ag | Cis-7,8-epoxy-2-methyl-octadecane prodn. - by electrochemical condensn. of pelargonic acid and cis-4-octene-di:oic acid ester, useful as insect sex attractant |
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