Method for synthesizing sex pheromone of peach fruit moth
Through the direct reaction method of Weinreb amide and Grignard reagent, the problem of difficult production of peach pheromones in the prior art is solved, and the effects of high yield, mild reaction and cheap raw materials are achieved.
Patent Information
- Application Number
- CN202411737296.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-29
- Publication Date
- 2025-03-07
AI Technical Summary
In the prior art, the synthesis method of peach cervical pheromone in peach snacks has problems such as harsh reaction conditions, low yield, expensive raw materials, and strong toxicity of raw materials, making it difficult to amplify production.
The target product ketone is directly obtained by reacting Weinreb amide and Grignard reagent, eliminating the step of oxidizing the secondary alcohol to obtain the ketone. The reaction is mild, the raw materials are cheap and easy to obtain, and it is suitable for amplification of production.
It achieves high yield, mild reaction conditions and cheap and easy-to-get raw materials, which are suitable for the large-scale production of peach pheromones.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of insect sex pheromone synthesis, and in particular to a method for synthesizing the sex pheromone of peach borer. Background Art
[0002] The peach fruit moth, also known as Carposina niponensis in Latin, belongs to the family Carpophoridae in the order Lepidoptera. It is widely distributed, has overlapping generations, and has few natural enemies. It mainly harms peach, apple, pear, hawthorn, jujube, plum and other fruit trees. It is listed as a quarantine pest in many countries, and the damage caused by the peach fruit moth is getting worse year by year.
[0003] The sex pheromone of peach borer was first isolated by Japanese scholars Tamaki et al. Its main component is cis-7-eicosen-11-one ((Z7)-Eicosen-11-one, referred to as Z7-20-11kt) (Formula 1), and the secondary component is cis-7-nonadecen-11-one (referred to as Z7-19-11kt) (Formula 2). However, Korean scholars have found that the sex attractant core with only the single component Z7-20-11kt has a higher trapping activity for peach borer.
[0004] Formula 1. Z7-20-11kt Formula 2. Z7-19-11kt The sex pheromone of peach borer has the advantages of high efficiency in trace amounts, strong specificity, no harm to natural enemies, and no resistance to pesticides, which can achieve green control of peach borer. Chemical synthesis is the main way to obtain sex pheromones of peach borer and other pests. At present, literature has reported a variety of synthesis methods for sex pheromone components of peach borer, but there are still obvious shortcomings and deficiencies.
[0005] For example, Ito et al. used 1-bromononan-2-yne and 3-oxododecanoic acid methyl ester to carry out nucleophilic substitution reaction under alkaline conditions and decarboxylation at high temperature to obtain eicosapenta-7-yn-11-one, which was selectively reduced to Z7-20-11kt in the presence of Lindlar catalyst. However, 1-bromononan-2-yne and 3-oxododecanoic acid methyl ester are not commercially available and require multiple steps to obtain. Moreover, the yield of the coupling reaction between the two is not high, making it difficult to scale up the preparation. The synthetic route is shown in the following formula: .
[0006] Yamamoto et al. used 1,1-diphenylphosphonium perchlorate as raw material and used tandem Wittig reaction to synthesize Z7-20-11kt. However, the yield of (Z)-11-(diphenylphosphino)-11-(methylthio)-7-undecene was only 30%. The synthesis route is shown in the following formula: .
[0007] Yang Xiaomei et al. used dihydrofuran as a raw material to obtain 3-hydroxybutyraldehyde, which was then subjected to a Wittig reaction. The resulting undecyl-4-ene-1-ol was oxidized by PCC to the corresponding olefinic aldehyde undecyl-4-ene-1-aldehyde, which was then subjected to an addition reaction with nonylmagnesium bromide to generate (cis-7)-eicosyl-7-ene-11-ol. Finally, the target product Z7-20-11kt was obtained by oxidation with PCC. The yield of the first step of this route is not high, the reproducibility is poor, and the heavy metal chromium oxidant PCC is used twice; the synthetic route is shown in the following formula: .
[0008] Liu Mengying et al. synthesized oct-1-yne and then reacted it with ethylene oxide to obtain deca-3-yne-1-ol. Then, a nucleophilic substitution reaction with potassium cyanide was used to generate the key intermediate 1-cyano-dec-3-yne. The latter reacted with nonylmagnesium bromide to obtain -20-7-yne-11-one. Finally, catalytic hydrogenation was used to reduce the acetylene bond to generate Z7-20-11kt. This route requires the use of acetylene and two Grignard reagents, especially the highly toxic potassium cyanide, which is not suitable for large-scale preparation. Its synthetic route is shown in the following formula: .
[0009] Xia et al. used 1-triphenylphosphine-2-propanone and 1-bromooctane to couple under the action of butyl lithium to generate 1-triphenylphosphine-undecan-2-one, which was then subjected to a Wittig reaction with nonan-2-ynaldehyde to obtain 20-7-yn-(9E)-ene-11-one. Then, trimethylsilyl chloride selectively reduced the conjugated double bond while retaining the acetylene bond to give 20-7-yn-11-one. Finally, in the presence of Lindlar catalyst, the acetylene bond was reduced to a cis double bond to obtain Z7-20-11kt. However, the key raw material nonan-2-ynaldehyde is not commercially available and requires multi-step reaction preparation; its synthetic route is shown in the following formula: In summary, although a variety of methods for synthesizing peach borer sex pheromones have been reported in the literature, there are problems such as harsh reaction conditions, low yield, expensive raw materials, and strong toxicity of raw materials, which make it difficult to scale up production. In order to meet the field test needs of green control of peach borer, it is necessary to develop a method for synthesizing peach borer sex pheromones suitable for scale-up production. Summary of the invention
[0010] In order to solve the problem that the synthesis method of peach pod moth sex pheromone in the prior art is difficult to scale up production, the present invention provides a synthesis method of peach pod moth sex pheromone, which directly obtains the target product ketone by reacting Weinreb amide and Grignard reagent, omitting the step of oxidizing secondary alcohol to obtain ketone, has mild reaction, and the raw materials are cheap and easily available, which is suitable for scale-up production.
[0011] The technical solution adopted by the present invention to solve its technical problem is: A method for synthesizing sex pheromone of peach borer, comprising the following steps: S1: reacting ethyl 4-bromobutyrate with triphenylphosphine as raw materials to obtain ethyl 4-triphenylphosphonium bromide butyrate; S2: the ethyl 4-triphenylphosphonium bromide butyrate reacts with n-heptanal in the presence of a base A to obtain ethyl cis-7-undecenoate; S3: The cis-7-undecenoic acid ethyl ester is hydrolyzed to obtain cis-7-undecenoic acid; S4: the cis-7-undecenoic acid reacts with thionyl chloride to obtain cis-7-undecenoyl chloride; S5: coupling the cis-7-undecenoyl chloride with N,O-dimethylhydroxylamine hydrochloride to obtain N-methyl-N-methoxy-cis-7-undecenoylamide; S6: The N-methyl-N-methoxy-cis-7-undeceneamide is reacted with nonylmagnesium bromide to obtain cis-7-eicosene-11-one.
[0012] Optionally, step S1 includes the following steps: S11: using acetonitrile as a solvent, adding the ethyl 4-bromobutyrate and the triphenylphosphine, heating to 90° C. in an oil bath, and reflux reaction to obtain a first reaction solution; S12: After the reaction is completed, the first reaction solution is concentrated under reduced pressure, petroleum ether is added to the crude product, and the mixture is stirred until a solid is precipitated, and the solid is filtered and dried to obtain the ethyl 4-triphenylphosphonium bromide butyrate.
[0013] Optionally, step S2 includes the following steps: S21: adding the ethyl 4-triphenylphosphonium bromide butyrate into a reaction bottle, and adding the base A under nitrogen protection and tetrahydrofuran as solvent, while stirring, to obtain a second reaction solution; S22: In an ice bath, add the n-heptanal dropwise to the second reaction solution, warm to room temperature to continue the reaction, quench the reaction, extract the aqueous phase with ethyl acetate, combine the organic phases, and concentrate under reduced pressure to obtain the cis-7-undecenoic acid ethyl ester.
[0014] Optionally, the base A is selected from at least one of potassium tert-butoxide, sodium ethoxide, sodium methoxide, and sodium dimethyl sulfoxide.
[0015] Optionally, the base A is potassium tert-butoxide.
[0016] Optionally, step S3 includes the following steps: S31: adding tetrahydrofuran, methanol, water and lithium hydroxide to the cis-7-undecenoic acid ethyl ester at room temperature, stirring to obtain a third reaction solution; S32: The third reaction liquid is concentrated under reduced pressure, the aqueous phase is extracted with dichloromethane, the pH of the aqueous phase after extraction is adjusted to 2-3 with dilute hydrochloric acid, the aqueous phase is extracted with ethyl acetate and then dried, and the reaction liquid is concentrated under reduced pressure again to obtain the cis-7-undecenoic acid.
[0017] Optionally, step S5 includes the following steps: S51: Add N,O-dimethylhydroxylamine hydrochloride and dichloromethane to a reaction bottle, and dropwise add base B to obtain a fourth reaction solution; S52: Add the cis-7-undecenoyl chloride to the fourth reaction liquid, then drop triethylamine, stir the reaction, quench the reaction, extract the aqueous phase with ethyl acetate, combine the organic phases, dry and concentrate under reduced pressure, and purify through silica gel column chromatography to obtain the N-methyl-N-methoxy-cis-7-undecenoylamide.
[0018] Optionally, the base B is selected from at least one of triethylamine, pyridine, N,N-dimethylpyridine and N,N-diisopropylethylamine.
[0019] Optionally, the base B is triethylamine.
[0020] Optionally, step S6 includes the following steps: S61: Under nitrogen protection, the N-methyl-N-methoxy-cis-7-undecenamide is added to a reaction bottle, and a tetrahydrofuran solution of nonylmagnesium bromide is added dropwise at 0° C. using tetrahydrofuran as a solvent to obtain a fifth reaction solution; S62: After the reaction is completed, the reaction is quenched, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, dried, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the cis-7-eicosene-11-one.
[0021] The beneficial effects of the present invention are: The method for synthesizing the sex pheromone of peach borer provided by the present invention has mild reaction conditions and cheap and readily available raw materials; the target product ketone is directly obtained by reacting Weinreb amide and Grignard reagent, and the step of obtaining the ketone by oxidizing secondary alcohol is omitted; the yield is high and the production is easy to be scaled up. DETAILED DESCRIPTION
[0022] The present invention is now further described in detail. The embodiments described below are exemplary and intended to be used to explain the present invention, but cannot be understood as limiting the present invention. All other embodiments obtained by ordinary technicians in this field without creative work based on the embodiments of the present invention belong to the scope of protection of the present invention.
[0023] In order to solve the problem that the synthesis method of peach borer sex pheromone in the prior art is difficult to scale up production, the present invention provides a synthesis method of peach borer sex pheromone, which comprises the following steps: S1: reacting ethyl 4-bromobutyrate with triphenylphosphine as raw materials to obtain ethyl 4-triphenylphosphonium bromide butyrate; S2: 4-triphenylphosphonium bromide butyric acid ethyl ester reacts with n-heptanal in the presence of a base, which is denoted as base A for easy distinction, to obtain cis-7-undecenoic acid ethyl ester; S3: cis-7-undecenoic acid ethyl ester is hydrolyzed to obtain cis-7-undecenoic acid; S4: cis-7-undecenoic acid reacts with thionyl chloride to obtain cis-7-undecenoyl chloride; S5: cis-7-undecenoyl chloride is coupled with N,O-dimethylhydroxylamine hydrochloride to obtain N-methyl-N-methoxy-cis-7-undecenoylamide; S6: N-methyl-N-methoxy-cis-7-undeceneamide reacts with nonylmagnesium bromide to obtain cis-7-eicosene-11-one.
[0024] The present invention provides a method for synthesizing the sex pheromone of peach borer, which uses ethyl 4-bromobutyrate (denoted as 1) as a starting material, and refluxes with triphenylphosphine to obtain a quaternary phosphonium salt (denoted as 2). In the presence of a base, the quaternary phosphonium salt and n-heptanal undergo a Wittig reaction to obtain cis-7-undecenoic acid ethyl ester (denoted as 3). Then, after hydrolysis with lithium hydroxide, cis-7-undecenoic acid ethyl ester is converted into cis-7-undecenoic acid (denoted as 4). The latter reacts with thionyl chloride to produce the corresponding acyl chloride (denoted as 5). Under the action of a base, the acyl chloride reacts with dimethylhydroxylamine hydrochloride to generate N-methyl-N-methoxy-cis-7-undecenoic acid amide (denoted as 6). Finally, Weinreb amide and nonylmagnesium bromide undergo an addition reaction to obtain cis-7-eicosene-11-one (Z7-20-11kt), the main component of the sex pheromone of peach borer. The synthesis route of the peach borer pheromone of the present invention is shown in the following formula: .
[0025] The method for synthesizing the sex pheromone of peach borer provided by the present invention has mild reaction conditions and cheap and readily available raw materials; the target product ketone is directly obtained by reacting Weinreb amide and Grignard reagent, and the step of obtaining the ketone by oxidizing secondary alcohol is omitted; the yield is high and the production is easy to be scaled up.
[0026] Specifically, the present invention preferably prepares ethyl 4-triphenylphosphonium bromide butyrate according to the following method, that is, preferably Step S1 includes the following steps: S11: using acetonitrile as solvent, adding ethyl 4-bromobutyrate and triphenylphosphine, heating to 90° C. in an oil bath, and reflux reaction to obtain a first reaction solution; S12: After the reaction is completed, the first reaction liquid is concentrated under reduced pressure, petroleum ether is added to the crude product, and the mixture is stirred until a solid is precipitated, which is then filtered and air-dried to obtain ethyl 4-triphenylphosphonium bromide butyrate.
[0027] The preferred method of the present invention is to prepare ethyl cis-7-undecenoate according to the following method, that is, the preferred step S2 comprises the following steps: S21: Add ethyl 4-triphenylphosphonium bromide butyrate to a reaction flask, and add base A under nitrogen protection and tetrahydrofuran as solvent while stirring to obtain a second reaction solution; S22: In an ice bath, n-heptanal was added dropwise to the second reaction solution, and the temperature was raised to room temperature to continue the reaction. The reaction was quenched, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, and concentrated under reduced pressure to obtain cis-7-undecenoic acid ethyl ester.
[0028] Specifically, step S2 can be performed as follows: Under nitrogen protection, tetrahydrofuran was used as solvent, 4-triphenylphosphonium bromide butyric acid ethyl ester was added, and base A was added under stirring at room temperature. After stirring for 30 minutes, the ice bath was cooled to 0-5°C, and n-heptanal was added dropwise. After the addition, the mixture was moved to room temperature for 1 hour. Water was added to quench, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, the organic phases were washed with saturated brine and dried. Spin dried to obtain crude cis-7-undecenoic acid ethyl ester, which was directly used in the next step.
[0029] In the present invention, the base A is preferably selected from at least one of potassium tert-butoxide, sodium ethoxide, sodium methoxide, and sodium dimethyl sulfoxide. It is further preferred that the base A is potassium tert-butoxide.
[0030] The preferred method for preparing cis-7-undecenoic acid of the present invention, that is, step S3 comprises the following steps: S31: adding tetrahydrofuran, methanol, water and lithium hydroxide to cis-7-undecenoic acid ethyl ester at room temperature, and stirring, preferably stirring for 2 hours, to obtain a third reaction solution; S32: The third reaction liquid is concentrated under reduced pressure, the aqueous phase is extracted with dichloromethane, the pH of the aqueous phase after extraction is adjusted to 2-3 with dilute hydrochloric acid, the aqueous phase is extracted with ethyl acetate and then dried, and the reaction mixture is concentrated under reduced pressure again to obtain cis-7-undecenoic acid.
[0031] The preferred method for preparing cis-7-undecenoyl chloride of the present invention, that is, step S4 comprises the following steps: Under nitrogen protection, cis-7-undecenoic acid and dichloromethane were added to the reaction flask in sequence, and dichlorothionyl was added dropwise. After reacting at room temperature for 3 hours, the mixture was concentrated under reduced pressure to obtain cis-7-undecenoyl chloride, which was directly used in the next step.
[0032] The preferred method for preparing N-methyl-N-methoxy-cis-7-undeceneamide of the present invention, that is, the preferred step S5 comprises the following steps: S51: Add N,O-dimethylhydroxylamine hydrochloride and dichloromethane to a reaction flask, and dropwise add a base (referred to as base B for easy distinction) to obtain a fourth reaction solution; S52: Add cis-7-undecenoyl chloride to the fourth reaction liquid, then drop triethylamine, stir the reaction, quench the reaction, extract the aqueous phase with ethyl acetate, combine the organic phases, dry and concentrate under reduced pressure, and purify by silica gel column chromatography to obtain N-methyl-N-methoxy-cis-7-undecenoylamide.
[0033] Specifically, this step can be performed as follows: Under nitrogen protection, N,O-dimethylhydroxylamine hydrochloride was added with dichloromethane as solvent. Triethylamine was added dropwise at -10°C, cis-7-undecenoyl chloride was added, and then base B was added dropwise. After addition, the reaction was carried out at -10°C for 1 hour, and then moved to room temperature for 1 hour. Water was added to quench the reaction. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined and washed with dilute hydrochloric acid and saturated brine in turn. After drying, the mixture was concentrated under reduced pressure to obtain N-methyl-N-methoxy-cis-7-undecenoylamide.
[0034] In the present invention, the base B is preferably selected from at least one of triethylamine, pyridine, N,N-dimethylpyridine and N,N-diisopropylethylamine, and the base B is further preferably triethylamine.
[0035] The preferred cis-7-eicosene-11-one (Z7-20-11kt) of the present invention is prepared according to the following method: Under nitrogen protection, add N-methyl-N-methoxy-cis-7-undeceneamide and dry tetrahydrofuran to the reaction bottle, cool the ice bath to 0°C, and drop nonylmagnesium bromide in tetrahydrofuran. React for 1 hour at 0°C. Quench the reaction with dilute hydrochloric acid and extract with ethyl acetate. Wash the organic phase with saturated sodium bicarbonate solution and saturated brine in turn. After drying, concentrate under reduced pressure. The crude product is purified by silica gel column chromatography to obtain the target product Z7-20-11kt.
[0036] That is, the preferred step S6 of the present invention comprises the following steps: S61: Under nitrogen protection, N-methyl-N-methoxy-cis-7-undeceneamide was added to a reaction flask, and a tetrahydrofuran solution of nonylmagnesium bromide was added dropwise at 0° C. using tetrahydrofuran as a solvent to obtain a fifth reaction solution; S62: After the reaction is completed, the reaction is quenched, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, dried, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain cis-7-eicosene-11-one (Z7-20-11kt).
[0037] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, specific embodiments of the present invention are described in detail below.
[0038] This embodiment provides a method for synthesizing sex pheromone of peach borer, comprising the following steps: S1: Add 4-bromobutyric acid ethyl ester (80g, 410 mmol), triphenylphosphine (118g, 451mmol, 1.1eq) and acetonitrile (200 mL) in a 500 mL single-mouth bottle, heat to 90°C in an oil bath, and reflux for 24 hours. Monitor by TLC and concentrate under reduced pressure. Add petroleum ether (300 mL) to the crude product and stir at room temperature until solid precipitates. Vacuum filter the obtained solid. Dry to obtain 4-triphenylphosphonium bromide butyric acid ethyl ester 2 (140g, yield 75%).
[0039] 1 H NMR (400 MHz, CDCl3): δ7.78–7.65 (m, 10H), 7.60 (td, J=7.5, 3.5Hz, 6H), 3.85–3.73 (m, 2H), 2.73 (t, J=6.7Hz, 2H), 1.87–1.76 (m, 2H), 1.10 (t, J=7.2Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ 172.79, 134.97, 134.94, 133.56, 133.47,130.42, 130.30, 118.23, 117.38, 33.21, 33.03,2 1.80, 17.84.
[0040] S2: In a 1000 mL three-necked flask protected by nitrogen, add 4-triphenylphosphonium bromide butyric acid ethyl ester 2 (140 g, 307 mmol) obtained in the previous step, tetrahydrofuran (400 mL), and add potassium tert-butoxide (37.8 g, 337.7 mmol, 1.1 eq) under stirring. After the addition, continue stirring for 30 minutes. Cool to 0-5°C in an ice bath, and add n-heptanal (38.5 g, 337.7 mmol, 1.1 eq) dropwise. After the addition, warm to room temperature and stir for 1 hour. Monitor by TLC, quench with water, extract the aqueous phase with ethyl acetate (2×150 mL), and wash the organic phases with saturated brine (2×150 mL) and dry with sodium sulfate. Spin dry. The crude product is purified by column chromatography to obtain pure cis-7-undecenoic acid ethyl ester 3 (78% yield).
[0041] 1 H NMR (400 MHz, CDCl3): δ5.46–5.27 (m, 2H), 4.11 (q, J=7.2Hz, 2H), 2.42–2.27 (m, 4H), 2.03 (q, J=6.4Hz, 2H), 1.36–1.22 (m, 11H), 0.92–0.83 (m,3H); 13 C NMR (101 MHz, CDCl3): δ173.4, 131.6, 127.4, 60.4, 34.5, 31.9, 29.7,29.1, 27.3, 22.9, 22.8, 14.4, 14.2.
[0042] S3: Add tetrahydrofuran (200 mL), methanol (100 mL), water (100 mL), lithium hydroxide (14.7 g, 704 mmol, 2 eq) to the crude product obtained in the previous step and stir at room temperature for 2 hours. Monitor by TLC and gas phase to confirm that the raw material reacts completely. Concentrate under reduced pressure. Extract the aqueous phase with dichloromethane (2×150 mL). Adjust the pH value of the aqueous phase to 2~3 with 2N dilute hydrochloric acid. The aqueous phase becomes turbid and is extracted with ethyl acetate (2×150 mL). The organic phase obtained by extraction is dried over sodium sulfate. Concentrate to obtain cis-7-undecenoic acid 4 (81% yield).
[0043] 1 H NMR (400 MHz, CDCl3): δ5.52–5.29 (m, 2H), 2.45–2.32 (m, J= 4.0Hz,4H), 2.04 (q, J=6.7Hz, 2H), 1.38–1.21 (m, 8H), 0.92–0.83 (m,3H); 13C NMR (101MHz, CDCl3): δ179.9, 132.0, 127.0, 34.3, 31.9, 29.7, 29.1, 27.3, 22.8, 22.6,14.2.
[0044] S4: Add cis-7-undecenoic acid 4 (30 g, 163 mmol) obtained in the previous step, dichloromethane (200 mL), and dropwise thionyl chloride (27 g, 228.2 mmol, 1.4 eq) into a 500 mL single-mouth bottle. React at room temperature for 3 hours, and monitor the reaction progress by gas phase. After the reaction of the raw materials is complete, concentrate under reduced pressure. Obtain cis-7-undecenoyl chloride 5, which is directly used in the next step.
[0045] S5: Add N,O-dimethylhydroxylamine hydrochloride (23.7 g, 244.5 mmol, 1.5 eq) and dichloromethane (200 mL) to a 500 mL single-mouth bottle. Cool to -10°C. Add triethylamine (24.7 g, 244.5 mmol, 1.5 eq) dropwise. Add the crude cis-7-undecenoyl chloride 5 obtained in the previous step. Add triethylamine (24.7 g, 244.5 mmol, 1.5 eq) dropwise. After addition, react at -10°C for 1 hour. React at room temperature for 1 hour. Monitor by TLC. Monitor the reaction progress by gas phase. After the reaction of the raw materials is complete, add water to quench the reaction. Extract the aqueous phase with ethyl acetate (2×150 mL). Combine the organic phases and wash with 1N dilute hydrochloric acid (150 mL) and saturated brine (2×100 mL) in turn, and dry over anhydrous sodium sulfate. Concentrate under reduced pressure. N-methyl-N-methoxy-cis-7-undeceneamide 6 (30 g, two-step yield 81%) was obtained.
[0046] 1 H NMR (400 MHz, CDCl3): δ5.44–5.30 (m, 2H), 3.65 (s, 3H), 3.15 (s,3H), 2.49–2.29 (m, 4H), 2.02 (q, J=6.5Hz, 2H), 1.36-1.16 (m, 10H), 0.84 (t, J=6.6Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ174.2, 131.3, 128.1, 61.2, 32.6, 32.1,31.8, 29.7, 29.0, 27.3, 22.7, 22.5, 14.1.
[0047] S6: Add N-methyl-N-methoxy-cis-7-undeceneamide 6 (30 g, 132 mmol) obtained in the previous step and dry tetrahydrofuran (150 mL) to a 1000 mL nitrogen-protected three-necked flask and cool to 0°C in an ice bath. Add 0.5 M nonylmagnesium bromide tetrahydrofuran solution (370 mL, 184.8 mmol, 1.4 eq) dropwise. Keep the temperature at 0°C for 1 hour. Add saturated 1N dilute hydrochloric acid (100 mL) to quench the reaction, and extract with ethyl acetate (2×150 mL). The organic phase is washed with saturated sodium bicarbonate solution (2×100 mL) and saturated brine (100 mL) in turn, and dried over anhydrous sodium sulfate. Concentrate under reduced pressure. The crude product is purified by silica gel column chromatography using a mixture of petroleum ether and ethyl acetate in a volume ratio of 20:1 as the eluent to obtain Z7-20-11kt (7) (35 g, 90% yield).
[0048] 1 H NMR (400 MHz, CDCl3): δ5.43-5.24 (m, 2H), 2.40–2.36 (m, 4H), 2.29(q, J=7.2Hz, 2H), 2.02 (q, J =7.0 Hz, 2H), 1.59–1.52 (m, 2H), 1.32–1.25 (m,20H), 0.87 (t, J=6.4 Hz, 6H); 13 C NMR (101 MHz CDCl3): δ211.1, 131.3, 127.9,43.1, 42.8, 32.0, 31.9, 29.8, 29.6, 29.6, 29.4, 29.4, 29.1, 27.3, 24.0, 22.8,22.8, 21.9, 14.2.
[0049] The difference between this embodiment and embodiment 1 is that toluene is used to replace acetonitrile in step S1; finally, 4-triphenylphosphonium bromide butyric acid ethyl ester 2 (143 g, yield 77%) is obtained.
[0050] The difference between this example and Example 1 is that the potassium tert-butoxide in step S2 is replaced with sodium methoxide to obtain pure cis-7-undecenoic acid ethyl ester 3 (65% yield).
[0051] The difference between this example and Example 1 is that the potassium tert-butoxide in step S2 is replaced with sodium ethoxide to obtain pure cis-7-undecenoic acid ethyl ester 3 (61% yield).
[0052] The difference between this example and Example 1 is that the triethylamine in step S5 is replaced with pyridine to obtain N-methyl-N-methoxy-cis-7-undeceneamide 6 (61% yield).
[0053] The difference between this example and Example 1 is that the triethylamine in step S5 is replaced with N,N-dimethylpyridine (DMAP) to obtain N-methyl-N-methoxy-cis-7-undeceneamide 6 (56% yield).
[0054] The difference between this example and Example 1 is that the triethylamine in step S5 is replaced with N,N-diisopropylethylamine (DIPEA) to obtain N-methyl-N-methoxy-cis-7-undeceneamide 6 (78% yield).
[0055] Based on the above ideal embodiments of the present invention, the relevant staff can make various changes and modifications without departing from the technical concept of the present invention through the above description. The technical scope of the present invention is not limited to the contents of the specification, and its technical scope must be determined according to the scope of the claims.
Claims
1. A method for synthesizing sex pheromone of peach borer, characterized in that: The steps include: S1: reacting ethyl 4-bromobutyrate with triphenylphosphine as raw materials to obtain ethyl 4-triphenylphosphonium bromide butyrate; S2: the ethyl 4-triphenylphosphonium bromide butyrate reacts with n-heptanal in the presence of a base A to obtain ethyl cis-7-undecenoate; S3: The cis-7-undecenoic acid ethyl ester is hydrolyzed to obtain cis-7-undecenoic acid; S4: the cis-7-undecenoic acid reacts with thionyl chloride to obtain cis-7-undecenoyl chloride; S5: coupling the cis-7-undecenoyl chloride with N,O-dimethylhydroxylamine hydrochloride to obtain N-methyl-N-methoxy-cis-7-undecenoylamide; S6: The N-methyl-N-methoxy-cis-7-undeceneamide is reacted with nonylmagnesium bromide to obtain cis-7-eicosene-11-one.
2. The method for synthesizing the sex pheromone of peach borer according to claim 1, characterized in that: Step S1 includes the following steps: S11: using acetonitrile as a solvent, adding the ethyl 4-bromobutyrate and the triphenylphosphine, heating to 90° C. in an oil bath, and reflux reaction to obtain a first reaction solution; S12: After the reaction is completed, the first reaction solution is concentrated under reduced pressure, petroleum ether is added to the crude product, and the mixture is stirred until a solid is precipitated, and the solid is filtered and dried to obtain the ethyl 4-triphenylphosphonium bromide butyrate.
3. The method for synthesizing the sex pheromone of peach borer according to claim 1, characterized in that: Step S2 includes the following steps: S21: adding the ethyl 4-triphenylphosphonium bromide butyrate into a reaction bottle, and adding the base A under nitrogen protection and tetrahydrofuran as solvent, while stirring, to obtain a second reaction solution; S22: In an ice bath, add the n-heptanal dropwise to the second reaction solution, warm to room temperature to continue the reaction, quench the reaction, extract the aqueous phase with ethyl acetate, combine the organic phases, and concentrate under reduced pressure to obtain the cis-7-undecenoic acid ethyl ester.
4. The method for synthesizing the sex pheromone of peach borer as claimed in claim 3, characterized in that: The base A is selected from at least one of potassium tert-butoxide, sodium ethoxide, sodium methoxide, and sodium dimethyl sulfoxide.
5. The method for synthesizing the sex pheromone of peach borer as claimed in claim 4, characterized in that: The base A is potassium tert-butoxide.
6. The method for synthesizing the sex pheromone of peach borer according to claim 1, characterized in that: Step S3 includes the following steps: S31: adding tetrahydrofuran, methanol, water and lithium hydroxide to the cis-7-undecenoic acid ethyl ester at room temperature, stirring to obtain a third reaction solution; S32: The third reaction liquid is concentrated under reduced pressure, the aqueous phase is extracted with dichloromethane, the pH of the aqueous phase after extraction is adjusted to 2-3 with dilute hydrochloric acid, the aqueous phase is extracted with ethyl acetate and then dried, and the reaction liquid is concentrated under reduced pressure again to obtain the cis-7-undecenoic acid.
7. The method for synthesizing the sex pheromone of peach borer according to claim 1, characterized in that: Step S5 includes the following steps: S51: Add N, O-dimethylhydroxylamine hydrochloride and dichloromethane to the reaction bottle, and dropwise add base B to obtain a fourth reaction solution; S52: Add the cis-7-undecenoyl chloride to the fourth reaction liquid, then drop triethylamine, stir the reaction, quench the reaction, extract the aqueous phase with ethyl acetate, combine the organic phases, dry and concentrate under reduced pressure, and purify through silica gel column chromatography to obtain the N-methyl-N-methoxy-cis-7-undecenoylamide.
8. The method for synthesizing the sex pheromone of peach borer according to claim 7, characterized in that: The base B is selected from at least one of triethylamine, pyridine, N, N-lutidine, and N, N-diisopropylethylamine.
9. The method for synthesizing the sex pheromone of peach borer according to claim 8, characterized in that: The base B is triethylamine.
10. The method for synthesizing the sex pheromone of peach borer according to claim 1, characterized in that: Step S6 includes the following steps: S61: Under nitrogen protection, the N-methyl-N-methoxy-cis-7-undecenamide is added to a reaction bottle, and a tetrahydrofuran solution of nonylmagnesium bromide is added dropwise at 0° C. using tetrahydrofuran as a solvent to obtain a fifth reaction solution; S62: After the reaction is completed, the reaction is quenched, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, dried, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the cis-7-eicosene-11-one.