Synthesis method of (5S,6R)-5,6-epoxyheptadec-2-yn-1-ol
Through the epoxidation and dephenyl reaction of (Z)-1-bromotetradecene and substituted phenyl propargyl ether, the problem of instability of intermediates in synthesis of (5S,6R)-5,6-epoxy-2-heptadecene-1-ol was solved, and an efficient and stable synthesis process was achieved, which was suitable for industrial production.
Patent Information
- Application Number
- CN202411794378.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-12-09
- Publication Date
- 2025-08-01
- Estimated Expiration
- 2044-12-09
AI Technical Summary
In the prior art, the synthesis method of (5S,6R)-5,6-epoxy-2-heptadecene-1-ol has the problem that key intermediates are unstable and it is difficult to achieve industrial production.
After the reaction of (Z)-1-bromotetradecene and substituted phenyl propargyl ether, the epoxidation and dephenyl reaction were carried out through the action of an epoxidation catalyst and an oxidant to obtain (5S,6R)-5,6-epoxy-2-heptadecene-1-ol.
It realizes an efficient and stable synthesis process, simplifies the purification steps, is suitable for industrial production, reduces the loss of the purification process, and is easy to operate.
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Figure CN119264078B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the fields of chemical production technology and biological pesticides, and in particular to a method for synthesizing (5S, 6R)-5,6-epoxy-2-heptadecyne-1-ol. Background Art
[0002] The American gypsy moth, Hyphantriacunea (Drury), belongs to the Lepidoptera order, Arctiidae family, and is an important international quarantine pest. It has a omnivorous diet, a large appetite, strong reproductive capacity, wide adaptability, rapid spread, and severe damage. The gypsy moth has a wide host range, favoring species such as poplar, mulberry, sycamore, and white ash maple. It also attacks broad-leaved species such as willow, locust, camptotheca acuminata, and Ailanthus altissima. Besides trees and fruit trees, it also harms crops and vegetables. The gypsy moth's larvae are voracious eaters, and during a major outbreak, they can consume entire plants overnight, resulting in stunted growth and development. In severe cases, it can even kill trees and cause crop and vegetable yield failures, causing serious damage.
[0003] The invasion and spread of the gypsy moth are diverse. Strengthening pest monitoring is fundamental to its prevention and control, crucial for timely implementation of preventive measures and preventing the spread of the disease. Using sex traps to capture and monitor adult male gypsy moths is a mature monitoring technique, offering highly accurate and effective results.
[0004] The main attractant active ingredients of the gypsy moth sex pheromone are (3Z,6Z,9S,10R)-9,10-epoxy-3,6-heneicosadiene and (3Z,6Z,9S,10R)-9,10-epoxy-1,3,6-heneicostriene. Both are obtained from the key intermediate (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol (4) through a five-step reaction. The reaction pathway is as follows:
[0005]
[0006] The key intermediate (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol (4) is a white solid at room temperature with a melting point of 69-70 °C. The reported synthetic method in the literature is as follows [J. Org. Chem. 2010, 75, 4619-4622]: In a solvent system of hexamethylphosphoric triamide and diethyl ether, using (2S,3R)-2,3-epoxytetradecyl trifluoroacetate and propargyl trimethylsilyl ether as raw materials and n-butyllithium as the base, (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol is synthesized. The (2S,3R)-2,3-epoxytetradecyl trifluoroacetate involved in this reaction is prone to deterioration in air after purification, difficult to preserve, and difficult to achieve large-scale production; therefore, it is of great practical significance to develop an efficient and stable method for synthesizing (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol and realize industrial production. Summary of the Invention
[0007] The purpose of the present invention is to provide a synthetic method of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol to solve the problems existing in the prior art.
[0008] To solve the above technical problems, the present invention provides the following technical solutions:
[0009] A synthetic method of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, wherein the synthetic method is to react (Z)-1-bromotetradecene (1) with a substituted phenyl propargyl ether to obtain intermediate 2, and then carry out an epoxidation reaction under the action of an epoxidation catalyst to obtain intermediate 3, and then remove the substituted phenyl under the action of an oxidant to obtain (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol (4).
[0010] The reaction formula of the synthetic method is:
[0011] ;
[0012] wherein R is hydrogen, C1-4 alkyl or C1-4 alkoxy, and R is mono-, di-, tri-, tetra- or penta-substituted.
[0013] A synthetic method of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, comprising the following steps:
[0014] (1) In an argon atmosphere, in the presence of copper(I) iodide, sodium iodide, cesium carbonate, and organic solvent 1, react (Z)-1-bromotetradecene with a substituted phenyl propargyl ether at room temperature. After the reaction is completed, add quenching agent 1 to quench the reaction, extract with organic extractant 1, combine the organic phases, wash with saturated brine, dry over anhydrous magnesium sulfate, and concentrate to obtain intermediate 2;
[0015] (2) Mix the intermediate 2 obtained in step (1), an epoxidation catalyst, and an organic solvent 2, then add a buffer solution and a tetrabutylammonium sulfate solution. After stirring evenly, add a potassium peroxymonosulfate solution and a potassium carbonate solution to react, add a quenching agent 2 to quench the reaction, extract with an organic extractant 2, combine the organic phases, wash with saturated brine, dry with anhydrous magnesium sulfate, and concentrate to obtain intermediate 3;
[0016] (3) Mix intermediate 3 and a mixed solvent, add an oxidizing agent to react, and obtain (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol after post-treatment after the reaction ends.
[0017] As an optimization, the general structural formula of the substituted phenyl propargyl ether described in step (1) is: , the number of Rs is one or more, and R is one of hydrogen, methyl, ethyl, isopropyl, and methoxy.
[0018] As an optimization, the organic solvent 1 described in step (1) is one of N,N-dimethylformamide and diethyl ether; the quenching agent 1 is a saturated aqueous ammonium chloride solution; the volume ratio of the quenching agent 1 to the organic solvent is 1:1; the organic extractant 1 is diethyl ether.
[0019] As an optimization, the dispersion concentration of (Z)-1-bromotetradecene in the organic solvent 1 is 0.05 - 0.5 g / mL, preferably 0.08 - 0.20 g / mL; the molar ratio of (Z)-1-bromotetradecene to the substituted phenyl propargyl ether is 1:(1 - 4); the molar ratio of (Z)-1-bromotetradecene, sodium iodide, cesium carbonate, and copper(I) iodide is 1:(1 - 3):(1 - 3):(1 - 3), preferably 1:(1 - 2):(1 - 2):(1 - 2); the reaction time is 3 h.
[0020] As an optimization, the epoxidation catalyst described in step (2) is tert-butyl (3a'R,5S,7a'R)-2',2'-dimethyl-2-7'-dioxatetrahydrospiro[oxazole-5,6'[1,3]dioxolane[4,5c]pyran]-3-carboxylate; the organic solvent 2 is obtained by mixing dimethyl ether and dipropylene glycol dimethyl ether in a volume ratio of 3:1; the preparation method of the buffer solution is: dissolving potassium carbonate and acetic acid in ethylenediaminetetraacetic acid solution respectively, dropping the ethylenediaminetetraacetic acid solution of acetic acid into the ethylenediaminetetraacetic acid solution of potassium carbonate, and adjusting to pH = 8; the tetrabutylammonium sulfate solution is composed of tetrabutylammonium sulfate and ethylenediaminetetraacetic acid, and its concentration is 0.005 - 0.015 g / mL, preferably 0.005 - 0.01 g / mL; the potassium peroxymonosulfate solution is composed of potassium peroxymonosulfate and ethylenediaminetetraacetic acid, and its concentration is 0.15 - 0.25 g / mL, preferably 0.15 - 0.2 g / mL; the potassium carbonate solution is composed of potassium carbonate and ethylenediaminetetraacetic acid, and its concentration is 0.3 - 0.6 g / mL, preferably 0.3 - 0.4 g / mL.
[0021] As an optimization, the molar ratio of the epoxidation catalyst described in step (2) to intermediate 2 is (5 - 10):1, preferably (6 - 7):1; the dispersion concentration of intermediate 2 in organic solvent 2 is 0.1 - 0.5 g / mL, preferably 0.12 - 0.20 g / mL; the molar ratio of intermediate 2 to tetrabutylammonium sulfate, potassium peroxymonosulfate, and potassium carbonate is 1:(0.3 - 0.6):(1.5 - 3):(3 - 5), preferably 1:(0.3 - 0.6):(1.5 - 3):(3 - 5); the quenching agent 2 is n-hexane, and the volume ratio of quenching agent 2 to the organic solvent is 1:1; the organic extractant 2 is n-hexane.
[0022] As an optimization, the stirring temperature in step (2) is -10°C; the reaction temperature is -10°C, and the reaction time is 3 - 6 h, preferably 4 - 5 h.
[0023] As an optimization, the mixed solvent described in step (3) is obtained by mixing water and acetonitrile in a mass ratio of 1:(5 - 20); the dispersion of intermediate 3 in the mixed solvent is 0.01 g / mL - 0.3 g / mL; the oxidant is one of ammonium cerium(IV) nitrate, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, and potassium monopersulfate; the molar ratio of the oxidant to (Z)-1-bromotetradec-1-ene is (3 - 10):1, the reaction time is 20 - 50 min, preferably 30 - 35 min; the reaction temperature is 0°C.
[0024] As an optimization, the post-treatment step described in step (3) is as follows: Quench the reaction with an aqueous solution of saturated sodium bicarbonate with a volume 1.5 - 4.0 times that of the mixed solvent, extract with ethyl acetate, combine the organic phases, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography. The eluent for column chromatography purification is obtained by mixing petroleum ether and ethyl acetate in a volume ratio of (5 - 20):1.
[0025] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:
[0026] (1) The reaction of a substituted phenyl propargyl ether containing a benzene ring structure with (Z)-1-bromotetradecene forms an intermediate 2 containing a benzene ring structure, which has a large difference in polarity from the intermediate 3 of the subsequent ring-closing reaction product, facilitating the convenient monitoring of the reaction in actual production.
[0027] (2) For the synthesis method of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol provided by the present invention, in steps (1) and (2), there is no need to perform column chromatography purification treatment after the reaction ends. Only simple post-treatment is required to obtain a high-yield product. The three-step reaction approximates the "one-pot" treatment method to obtain the final product (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, reducing the loss during the purification process, with simple operation and being suitable for large-scale production;
[0028] (3) The reaction conditions for the ammonium cerium nitrate de-substituted phenyl reaction are mild and controllable, and the yield is good. Description of the Drawings
[0029] Figure 1 It is the nuclear magnetic resonance detection spectrum of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol prepared in Comparative Example 1; wherein, the abscissa is the chemical shift, with the unit of ppm; the ordinate is the signal intensity; and the data under the peaks in the spectrum are the integral areas of the peaks. Detailed Embodiments
[0030] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.
[0031] The epoxidation catalyst used in the following examples is tert-butyl (3a'R,5S,7a'R)-2',2'-dimethyl-2-7'-dioxatetrahydrospiro[oxazole-5,6'[1,3]dioxolane[4,5c]pyran]-3-carboxylate; the organic solvent 2 is obtained by mixing dimethyl ether and dipropylene glycol dimethyl ether in a volume ratio of 3:1; the preparation method of the buffer solution used is as follows: potassium carbonate and acetic acid are respectively dissolved in ethylenediaminetetraacetic acid solution, the ethylenediaminetetraacetic acid solution of acetic acid is added dropwise to the ethylenediaminetetraacetic acid solution of potassium carbonate, and the pH is adjusted to 8; the eluent for column chromatography purification used is obtained by mixing petroleum ether and ethyl acetate in a volume ratio of 10:1. Example 1:
[0032] A method for synthesizing (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, the synthesis method comprising the following steps:
[0033] (1) Dissolve 0.76 g of cuprous iodide, 0.60 g of sodium iodide, and 1.30 g of cesium carbonate in 15 mL of N,N-dimethylformamide, add dropwise a 5 mL N,N-dimethylformamide solution of 0.64 g of phenyl propargyl ether, stir well after the addition, and then add dropwise a 5 mL N,N-dimethylformamide solution of 1.08 g of (Z)-1-bromotetradecene, react at room temperature for 3 h, add 25 mL of saturated ammonium chloride aqueous solution to quench the reaction, extract with diethyl ether, combine the organic phases, wash once with saturated brine, dry over anhydrous magnesium sulfate, filter, and concentrate to obtain intermediate 2;
[0034] (2) Dissolve intermediate 2 and 0.185 g of the epoxidation catalyst in 10 mL of organic solvent 2, add 6 mL of the buffer solution and 5 mL of an ethylenediaminetetraacetic acid solution of 0.033 g of tetrabutylammonium sulfate, stir at -10 °C, then add dropwise 20 mL of an ethylenediaminetetraacetic acid solution of 3.95 g of potassium peroxymonosulfate and 5 mL of an ethylenediaminetetraacetic acid solution of 2 g of potassium carbonate. After the addition is complete, react at -10 °C for 4 h, add 60 mL of n-hexane to quench the reaction, extract with n-hexane, combine the organic phases, wash once with saturated brine solution, dry over anhydrous magnesium sulfate, and concentrate to obtain intermediate 3;
[0035] (3) Dissolve intermediate 3 in a mixed solvent of acetonitrile / water (30 mL / 3 mL), cool to 0 °C, add 4.63 g of ammonium cerium(IV) nitrate, stir for 0.5 h, add 60 mL of saturated sodium bicarbonate aqueous solution to quench the reaction, extract with ethyl acetate, combine the organic phases, wash once with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography to obtain 0.79 g of (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, with a yield of 68%.
[0036] Comparative Example 1:
[0037] A synthetic method of (5S,6R)-5,6-epoxyheptadec-2-yn-1-ol, the synthetic method comprising the following steps:
[0038] (1) Dissolve 0.76 g of cuprous iodide, 0.6 g of sodium iodide, and 1.3 g of cesium carbonate in 15 mL of N,N-dimethylformamide, add dropwise a 5 mL N,N-dimethylformamide solution of 0.64 g of p-methoxyphenyl propargyl ether. After the addition is complete, stir well, then add dropwise a 5 mL N,N-dimethylformamide solution of 1.08 g of (Z)-1-bromotetradecene. React at room temperature for 3 h, add 25 mL of saturated ammonium chloride aqueous solution to quench the reaction, extract with diethyl ether, combine the organic phases, wash once with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography to obtain 1.28 g of intermediate 2 with a yield of 90%. The characterization data are as follows:
[0039] 1HNMR(400MHz,Chloroform-d)δ6.94(ddd,J=9.3,4.7,2.2Hz,2H),6.89–6.80(m,2H),5.82–5.60(m,1H),5.53–5.35(m,1H),4.72–4.58(m,2H),3.79(s,3H),3.16–2.92(m,2H),2.03(t,J=7.9Hz,1H),1.56–1.45(m,1H),1.28(d,J=3.8Hz,19H),0.91(t,J=6.7Hz,3H);
[0040] (2) Dissolve 1.28 g of intermediate 2 and 0.185 g of epoxidation catalyst in 10 mL of organic solvent 2, add 6 mL of buffer solution and 5 mL of an ethylenediaminetetraacetic acid solution of 0.033 g of tetrabutylammonium sulfate. After the mixture is stirred well at -10 °C, add dropwise 20 mL of an ethylenediaminetetraacetic acid aqueous solution of 3.95 g of potassium peroxymonosulfate and 5 mL of an ethylenediaminetetraacetic acid aqueous solution of 2 g of potassium carbonate. After the addition is complete, react at -10 °C for 4 h, add 60 mL of n-hexane to quench the reaction, extract with n-hexane, combine the organic phases, wash once with saturated brine solution, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography to obtain 1.19 g containing intermediate 3 with a yield of 89%; The characterization data are as follows:
[0041] 1H NMR (400 MHz, Chloroform-d) δ 6.98–6.90 (m, 2H), 6.89–6.81 (m, 2H), 4.65 (t, J = 2.2 Hz, 2H), 3.79 (s, 3H), 3.15 (ddd, J = 7.0, 5.6, 4.1 Hz, 1H), 2.97 (td, J = 5.9, 4.0 Hz, 1H), 2.64 (ddt, J = 17.2, 5.7, 2.2 Hz, 1H), 2.36 (ddt, J = 17.2, 7.0, 2.2 Hz, 1H), 1.57–1.18 (m, 21H), 0.90 (t, J = 6.7 Hz, 3H);
[0042] Dissolve 1.19 g of Intermediate 3 in a mixed solvent of acetonitrile / water (10 mL / 1 mL), cool to 0 °C, add 4.63 g of ammonium cerium(IV) nitrate, stir for 0.5 h, add 40 mL of saturated aqueous sodium bicarbonate solution to quench the reaction, extract with ethyl acetate, combine the organic phases, wash once with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography to obtain 1.08 g of (5S,6R)-5,6-epoxyheptadec-2-yn-1-ol with a yield of 93%. The characterization data are as follows:
[0043] 1H NMR (400 MHz, Chloroform-d) δ 4.29 (t, J = 2.2 Hz, 2H), 3.16 (ddd, J = 6.8, 5.8, 4.1 Hz, 1H), 2.99 (td, J = 5.9, 4.1 Hz, 1H), 2.62 (ddt, J = 17.1, 5.8, 2.2 Hz, 1H), 2.37 (ddt, J = 17.1, 6.9, 2.2 Hz, 1H), 1.56–1.10 (m, 21H), 0.98–0.83 (m, 3H).
[0044] Comparative Example 2:
[0045] A method for synthesizing (5S,6R)-5,6-epoxyheptadec-2-yn-1-ol, the synthesis method comprising the following steps:
[0046] (1) 2.28 g of cuprous iodide, 1.80 g of sodium iodide, and 3.90 g of cesium carbonate were dissolved in 45 mL of N,N-dimethylformamide. A 15 mL N,N-dimethylformamide solution of 1.92 g of phenyl propargyl ether was added dropwise. After the addition, the mixture was stirred thoroughly, and then a 15 mL N,N-dimethylformamide solution of 3.24 g of (Z)-1-bromotetradecene was added dropwise. The reaction was carried out at room temperature for 3 h. The reaction was quenched by adding 75 mL of saturated ammonium chloride aqueous solution. The mixture was extracted with diethyl ether. The organic phases were combined, washed once with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography to obtain 3.72 g of intermediate 2 with a yield of 87%. The characterization data are as follows: 1H NMR (400 MHz, Chloroform-d) δ 6.94 (ddd, J = 9.3, 4.7, 2.2 Hz, 2H), 6.89–6.80 (m, 2H), 5.82–5.60 (m, 1H), 5.53–5.35 (m, 1H), 4.72–4.58 (m, 2H), 3.79 (s, 3H), 3.16–2.92 (m, 2H), 2.03 (t, J = 7.9 Hz, 1H), 1.56–1.45 (m, 1H), 1.28 (d, J = 3.8 Hz, 19H), 0.91 (t, J = 6.7 Hz, 3H);
[0047] (2) 3.72 g of intermediate 2 synthesized in Example 1 and 0.54 g of epoxidation catalyst were dissolved in 30 mL of organic solvent 2. 18 mL of buffer solution and 15 mL of an ethylenediaminetetraacetic acid solution of 0.10 g of tetrabutylammonium sulfate were added. After the mixture was stirred thoroughly at -10 °C, a 60 mL ethylenediaminetetraacetic acid solution of 11.42 g of potassium peroxymonosulfate and a 15 mL ethylenediaminetetraacetic acid solution of 5.80 g of potassium carbonate were added dropwise. After the addition, the reaction was carried out at -10 °C for 4 h. The reaction was quenched by adding 180 mL of n-hexane. The mixture was extracted with n-hexane. The organic phases were combined, washed once with saturated brine solution, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography to obtain 3.34 g of intermediate 3 with a yield of 86%. The characterization data are as follows:
[0048] 1H NMR (400 MHz, Chloroform-d) δ 6.98–6.90 (m, 2H), 6.89–6.81 (m, 2H), 4.65 (t, J = 2.2 Hz, 2H), 3.79 (s, 3H), 3.15 (ddd, J = 7.0, 5.6, 4.1 Hz, 1H), 2.97 (td, J = 5.9, 4.0 Hz, 1H), 2.64 (ddt, J = 17.2, 5.7, 2.2 Hz, 1H), 2.36 (ddt, J = 17.2, 7.0, 2.2 Hz, 1H), 1.57–1.18 (m, 21H), 0.90 (t, J = 6.7 Hz, 3H);
[0049] (3) Dissolve 3.34 g of Intermediate 3 in a mixed solvent of acetonitrile / water (10 mL / 1 mL), cool to 0 °C, add 9.51 g of ammonium cerium(IV) nitrate, stir for 0.5 h, quench the reaction with 40 mL of saturated sodium bicarbonate aqueous solution, extract with ethyl acetate, combine the organic phases, wash once with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography to obtain 2.24 g of (5S,6R)-5,6-epoxyheptadec-2-yne-1-ol with a yield of 94%.
[0050] The specific embodiments described above further elaborate on the purpose, technical solutions, and beneficial effects of the present invention. It should be understood that the above are only specific embodiments of the present invention and are not used to limit the protection scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.
Claims
1. A method for synthesizing (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol, characterized in that, The synthesis method is as follows: (Z)-1-bromotetradecene (1) reacts with a substituted phenyl propargyl ether to obtain intermediate 2, then an epoxidation reaction occurs under the action of an epoxidation catalyst to obtain intermediate 3, and then the substituted phenyl is removed under the action of an oxidant to obtain (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol (4). The reaction formula of the synthesis method is as follows: ； Copper(I) iodide, sodium iodide, and cesium carbonate are also added during the reaction of (Z)-1-bromotetradecene (1) and the substituted phenyl propargyl ether; the molar ratio of (Z)-1-bromotetradecene, sodium iodide, cesium carbonate, and copper(I) iodide is 1:(1-2):(1-2):(1-2). The general structural formula of the substituted phenyl propargyl ether is as follows: , the number of R is one or more, and R is one of hydrogen, methyl, ethyl, isopropyl, and methoxy; The epoxidation catalyst is tert-butyl (3a'R,5S,7a'R)-2',2'-dimethyl-2,7'-dioxatetrahydrospiro[oxazole-5,6'[1,3]dioxolane[4,5c]pyran]-3-carboxylate.
2. The synthesis method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 1, wherein It includes the following steps: (1) In an argon atmosphere, in the presence of copper(I) iodide, sodium iodide, cesium carbonate, and organic solvent 1, (Z)-1-bromotetradecene and the substituted phenyl propargyl ether are reacted at room temperature. After the reaction is completed, quenching agent 1 is added to quench the reaction. After extraction with organic extractant 1, the organic phases are combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated to obtain intermediate 2. (2) Intermediate 2 obtained in step (1), the epoxidation catalyst, and organic solvent 2 are mixed evenly, then a buffer solution and a tetrabutylammonium sulfate solution are added, and after stirring evenly, a potassium peroxymonosulfate solution and a potassium carbonate solution are added for reaction. Quenching agent 2 is added to quench the reaction. After extraction with organic extractant 2, the organic phases are combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated to obtain intermediate 3. (3) Intermediate 3 and the mixed solvent are mixed evenly, an oxidant is added for reaction, and after the reaction is completed, (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol is obtained through post-treatment.
3. The synthetic method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The organic solvent 1 in step (1) is one of N,N-dimethylformamide and diethyl ether; the quenching agent 1 is a saturated aqueous ammonium chloride solution; the volume ratio of the quenching agent 1 to the organic solvent is 1:1; the organic extractant 1 is diethyl ether.
4. The synthesis method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The dispersion concentration of (Z)-1-bromotetradecene in organic solvent 1 in step (1) is 0.05-0.5 g / mL; the molar ratio of (Z)-1-bromotetradecene to the substituted phenyl propargyl ether is 1:(1-4); the reaction time is 3 h.
5. The synthetic method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The organic solvent 2 described in step (2) is obtained by mixing dimethyl ether and dipropylene glycol dimethyl ether at a volume ratio of 3:1; the preparation method of the buffer solution is as follows: potassium carbonate and acetic acid are respectively dissolved in ethylenediaminetetraacetic acid solution, and the ethylenediaminetetraacetic acid solution of acetic acid is dropped into the ethylenediaminetetraacetic acid solution of potassium carbonate and adjusted to pH = 8; the tetrabutylammonium sulfate solution is composed of tetrabutylammonium sulfate and ethylenediaminetetraacetic acid, and its concentration is 0.005 - 0.015 g / mL; the potassium peroxymonosulfate solution is composed of potassium peroxymonosulfate and ethylenediaminetetraacetic acid, and the concentration is 0.15 - 0.25 g / mL; the potassium carbonate solution is composed of potassium carbonate and ethylenediaminetetraacetic acid, and the concentration is 0.3 - 0.6 g / mL.
6. The synthetic method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The molar ratio of the epoxidation catalyst to intermediate 2 described in step (2) is (5 - 10):1; the dispersion concentration of intermediate 2 in organic solvent 2 in step (2) is 0.1 - 0.5 g / mL; the molar ratio of intermediate 2 to tetrabutylammonium sulfate, potassium peroxymonosulfate, and potassium carbonate is 1:(0.3 - 0.6):(1.5 - 3):(3 - 5); the quenching agent 2 is n - hexane, and the volume ratio of quenching agent 2 to the organic solvent is 1:6; the organic extractant 2 is n - hexane.
7. The synthetic method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, wherein, The stirring temperature in step (2) is - 10 °C; the reaction temperature is - 10 °C, and the reaction time is 3 - 6 h.
8. The synthesis method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The mixed solvent described in step (3) is obtained by mixing water and acetonitrile at a mass ratio of 1:(5 - 20); the dispersion degree of intermediate 3 in the mixed solvent is 0.01 g / mL - 0.3 g / mL; the oxidant is one of ammonium cerium(IV) nitrate, 2,3 - dichloro - 5,6 - dicyano - 1,4 - benzoquinone, and potassium monopersulfate; the molar ratio of the oxidant to (Z) - 1 - bromotetradec - 1 - ene is (3 - 10):1, and the reaction time is 20 - 50 min; the reaction temperature is 0 °C.
9. The synthesis method of a (5S,6R)-5,6-epoxy-2-heptadecyn-1-ol according to claim 2, characterized in that, The post - treatment step described in step (3) is as follows: add a saturated sodium bicarbonate aqueous solution with a volume 1.5 - 4.0 times that of the mixed solvent to quench the reaction, extract with ethyl acetate, combine the organic phases, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and purify by column chromatography. The eluent for column chromatography purification is obtained by mixing petroleum ether and ethyl acetate at a volume ratio of (5 - 20):1.