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WO2024040754A1 - Procédé de synthèse de cis-2-méthyl-7-octadécène et de cis-7,8-époxy-2-méthyloctadécane - Google Patents

Procédé de synthèse de cis-2-méthyl-7-octadécène et de cis-7,8-époxy-2-méthyloctadécane Download PDF

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Publication number
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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Prior art keywords
cis
methyl
octadecene
synthesis method
reaction
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English (en)
Chinese (zh)
Inventor
郝德君
高淑贤
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Nanjing Fanmao Biotechnology Co Ltd
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Nanjing Fanmao Biotechnology Co Ltd
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    • 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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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epoxy Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention relève du domaine technique de la synthèse organique, et concerne un procédé de synthèse de cis-2-méthyl-7-octadécène et de cis-7,8-époxy-2-méthyloctadécane. La présente invention utilise des sels de N-sulfonylhydrazone et de phosphine comme matières premières, ce qui permet d'obtenir du cis-2-méthyl-7-octadécène par un procédé en une étape sous l'action d'une base organique sans générer de trans-2-méthyl-7-octadécène. Le rendement et la pureté du cis-2-méthyl-7-octadécène obtenu selon la présente invention sont tous deux élevés, le rendement du cis-2-méthyl-7-octadécène est de 68 à 96 %, et la pureté du cis-2-méthyl-7-octadécène est supérieure à 98,8 %. Le cis-2-méthyl-7-octadécène a une pureté élevée, le rendement et la pureté du cis-7,8-époxy-2-méthyloctadécane obtenus selon la présente invention sont tous deux élevés, le rendement du cis-7,8-époxy-2-méthyloctadécane est supérieur à 90 %, et la pureté du cis-7,8-époxy-2-méthyloctadécane est supérieure à 99 %.
PCT/CN2022/131263 2022-08-24 2022-11-11 Procédé de synthèse de cis-2-méthyl-7-octadécène et de cis-7,8-époxy-2-méthyloctadécane Ceased WO2024040754A1 (fr)

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CN202211016165.9 2022-08-24
CN202211016165.9A CN115353437B (zh) 2022-08-24 2022-08-24 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

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Citations (2)

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Publication number Priority date Publication date Assignee Title
US5463149A (en) * 1993-07-20 1995-10-31 Shin-Etsu Chemical Co., Ltd. 1-halo-cis-3-tetradecenes and processes for the preparation of cis-olefin compounds by using same
US20130231499A1 (en) * 2012-03-05 2013-09-05 California Institute Of Technology Synthesis of z-olefin-containing lepidopteran insect pheromones

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BE788547A (fr) * 1971-09-10 1973-03-08 Bayer Ag Procede de preparation de cis-7,8-epoxy-2-methyloctadecane
DE2758882A1 (de) * 1977-12-30 1979-07-05 Basf Ag Verfahren zur herstellung von cis-7,8-epoxy-2-methyloctadecan
EP0990653B1 (fr) * 1997-05-30 2004-09-15 Banyu Pharmaceutical Co., Ltd. Derives de 2-0xoimidazole
ITMI20031975A1 (it) * 2003-10-14 2005-04-15 Ind Chimica Srl Processo per la preparazione del d-cloprostenolo
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CN102321050B (zh) * 2011-06-02 2014-08-13 厦门大学 一种舞毒蛾性信息素的合成方法
CN110724042A (zh) * 2019-12-09 2020-01-24 中国林业科学研究院森林生态环境与保护研究所 一种杨小舟蛾性信息素活性成分的合成方法

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US5463149A (en) * 1993-07-20 1995-10-31 Shin-Etsu Chemical Co., Ltd. 1-halo-cis-3-tetradecenes and processes for the preparation of cis-olefin compounds by using same
US20130231499A1 (en) * 2012-03-05 2013-09-05 California Institute Of Technology Synthesis of z-olefin-containing lepidopteran insect pheromones

Non-Patent Citations (2)

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NARAYANA C., REDDY N. K., KABALKA G. W.: "Sodium Percarbonate: A Mild Reagent for Conversion of Tosylhydrazones and Nitroalkanes to Carbonyl Compounds", SYNTHETIC COMMUNICATIONS, vol. 22, no. 17, 31 December 1992 (1992-12-31), US , pages 2587 - 2592, XP009553229, ISSN: 0039-7911, DOI: 10.1080/00397919208021655 *

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