Synthesis method of cis-5-octylene-1-alcohol
The synthesis of cis-5-octen-1-ol via leaf alcohol with thionyl chloride, magnesium shavings, and red aluminum solves the problems of high cost and safety risks in existing technologies, and enables efficient and low-cost industrial production.
Patent Information
- Application Number
- CN202511682642.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-17
- Publication Date
- 2026-02-10
AI Technical Summary
Existing methods for synthesizing cis-5-octen-1-ol suffer from problems such as the need for ultra-low temperatures, expensive lithium reagents, poor selectivity, low yield, and high safety risks, making them unsuitable for industrial production.
Using leaf alcohol as the starting material, it reacts with thionyl chloride to generate 1-chloro-(Z)-3-hexene, which then reacts with magnesium shavings and iodine to form a Grignard reagent, followed by reaction with ethyl bromoacetate, and finally reduced by red aluminum to generate cis-5-octen-1-ol.
The synthesis of cis-5-octen-1-ol under mild conditions was achieved with a total yield of 72%, making it suitable for industrial production. It is low-cost and environmentally friendly.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of fine chemical engineering technology, and in particular to a method for synthesizing cis-5-octen-1-ol. Background Technology
[0002] cis-5-octen-1-ol is a synthetic flavoring agent used in the formulation of various fruit and vegetable flavorings. Studies have shown that it has a strong earthy aroma and is commonly found in various foods, such as fruits, vegetables, and spices. It has numerous applications in the flavoring and fragrance industry, particularly in perfumes, colognes, and baked goods as a flavoring and flavoring agent.
[0003] However, there are very few publications specifically studying the synthesis of cis-5-octen-1-ol. After literature search, the following synthetic routes were found, but all of them have certain limitations: Currently, the reported method (Journal of Organic Chemistry, vol. 78, 24p. 12735-12749) uses δ-valerolactone as the starting material, first reacting it with DIBAL-H, then with n-PrPPh3Br and n-BuLi to generate the target product. The synthetic route is as follows: This route has drawbacks: it requires ultra-low temperatures, resulting in high energy costs; it uses lithium reagents, which are expensive; and it exhibits selectivity at the double bond (the literature ratio is Z:E=7:1), making it unsuitable for industrial production.
[0004] The literature (Agricultural and Biological Chemistry, vol.48, 4 pp. 849-856) provides a method: using leaf alcohol as the starting material, it is first reacted with thionyl chloride to obtain a chlorinated derivative, then a Grignard reagent is prepared, and finally reacted with ethylene oxide to obtain the target product. The synthetic route is as follows: This route has drawbacks: the yield is low, resulting in high costs; ethylene oxide is a gas that is toxic and explosive, and is classified as a Group 1 carcinogen, posing certain safety risks.
[0005] Therefore, it is of great significance to find new, environmentally friendly, low-cost synthesis methods suitable for industrial production. Summary of the Invention
[0006] To address the shortcomings of existing technologies, this invention provides a method for synthesizing cis-5-octen-1-ol that is environmentally friendly, low-cost, and suitable for industrial production.
[0007] In order to achieve the objective of this invention, the following solution is proposed: A method for synthesizing cis-5-octen-1-ol, comprising the following steps: Step 1: Using leaf alcohol as the starting material, a substitution reaction is carried out with thionyl chloride to obtain 1-chloro-(Z)-3-hexene, specifically: Dichloromethane, leaf alcohol, and N,N-dimethylformamide were mixed evenly. The mixture was cooled to 15℃~25℃, and thionyl chloride was added dropwise. The mixture was stirred for 2 hours. The reaction solution was quenched in ice water, separated, washed with water, dried, filtered with desiccant, and distilled under reduced pressure to obtain 1-chloro-(Z)-3-hexene.
[0008] Step 2: The intermediate 1-chloro-(Z)-3-hexene obtained in Step 1 is reacted with magnesium shavings to obtain cis-3-hexene magnesium chloride Grignard reagent. The Grignard reagent is then reacted with ethyl bromoacetate under catalytic conditions to obtain ethyl cis-5-octenate. Specifically: Tetrahydrofuran, magnesium shavings, and iodine were mixed, purged with nitrogen, and heated to 60℃~65℃. A small amount of 1-chloro-(Z)-3-hexene was added dropwise. After the system was initiated, the remaining 1-chloro-(Z)-hexene was added dropwise. The reaction was stirred at 60℃~65℃ for 2 hours. After the reaction was completed, the temperature was lowered to -10℃~0℃, and cuprous iodide was added all at once. Ethyl bromoacetate was then added dropwise. The reaction was stirred at -10℃~0℃ for 2 hours. After the reaction was completed, the reaction solution was slowly poured into an ammonium chloride aqueous solution to quench it. The solution was separated, washed with water, dried, filtered with a desiccant, and then distilled under reduced pressure. After distillation under reduced pressure, ethyl maleate (cis-5-octenate) was obtained.
[0009] Step 3: The intermediate obtained in step 2 is subjected to a reduction reaction with red aluminum, specifically: Ethyl cis-5-octenate was mixed with toluene and cooled to 0℃~10℃. Red aluminum toluene solution was slowly added dropwise and the mixture was stirred at 0℃~10℃ for 2 hours. The reaction solution was then slowly poured into ice water to quench the reaction mixture. The mixture was separated, washed with water, dried, filtered to remove the desiccant, and then distilled under reduced pressure to obtain cis-5-octen-1-ol.
[0010] The advantages of this invention are that the synthetic route of this invention has mild reaction conditions, low cost, and is suitable for industrial production, and the total yield of the three steps can reach 72%. Detailed Implementation
[0011] Example 1 Step 1: Synthesis of 1-chloro-(Z)-3-hexene 100 g (1.0 mol) of leaf alcohol was added to a 500 mL four-necked flask, followed by 300 g of dichloromethane and 3.6 g of N,N-dimethylformamide. The mixture was stirred for 10 min until homogeneous. The temperature was then lowered to 15℃~25℃. After the temperature stabilized, 125 g (1.05 mol) of thionyl chloride was slowly added dropwise. After the addition was complete, the temperature in the reaction flask was maintained at 15℃~25℃ for 2 h. When the gas phase analysis showed that the leaf alcohol content was less than 0.5%, the reaction was terminated. The reaction solution was slowly poured into 300 g of water for quenching. The mixture was separated, and the aqueous phase was back-extracted with dichloromethane, the organic phase was washed with water, dried over anhydrous Mg2SO4, and distilled under reduced pressure to obtain 112 g of 1-chloro-(Z)-3-hexene with a purity >97% and a yield of 95%.
[0012] Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture with nitrogen three times, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. The reaction endpoint is reached when the 1-chloro-(Z)-3-hexene content is less than 1.0% as detected by gas chromatography. The temperature was lowered to -10℃ to 0℃, and 11g (0.04mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -10℃ to 0℃ for 1 to 2 hours. The content of ethyl bromoacetate was detected by gas phase analysis as <1%. After the reaction was completed, the reaction solution was transferred in batches to ammonium chloride aqueous solution for quenching. The organic phase was retained, and the aqueous phase was extracted with toluene. The organic phase was washed with water, dried, and distilled under reduced pressure to obtain crude ethyl cis-5-octenate. The crude product was then purified by reduced pressure distillation to obtain 115g of ethyl cis-5-octenate with a purity >97% and a yield of 80%.
[0013] Step 3: Synthesis of cis-5-octen-1-ol 77 g (0.45 mol) of ethyl cis-5-octenate was added to a 1000 mL four-necked flask, followed by 300 g of toluene. The temperature inside the reaction flask was lowered to 0-10 °C. After the temperature stabilized, 127 g (0.47 mol, 70 wt% toluene solution) of red aluminum toluene solution was slowly added dropwise. The temperature of the reaction system was controlled at 0-10 °C during the dropwise addition. After the dropwise addition was completed, the reaction was maintained at 0-10 °C for 1-2 hours. The content of ethyl cis-5-octenate was <0.5% by gas phase analysis. After the reaction was completed, the reaction solution was transferred in batches to dilute hydrochloric acid for quenching. After quenching, the mixture was allowed to stand and separated. The upper organic phase was retained. The organic phase was washed with water, dried, and concentrated to recover toluene, yielding crude cis-5-octen-1-ol. The crude product was then subjected to vacuum distillation to obtain 56 g of cis-5-octen-1-ol with a purity >97% and a yield of 95%.
[0014] Comparative Example 1 Step 1: Synthesis of 1-chloro-(Z)-3-hexene 100 g (1.0 mol) of leaf alcohol was added to a 500 mL four-necked flask, followed by 300 g of dichloromethane and 3.6 g of N,N-dimethylformamide. The mixture was stirred for 10 min until homogeneous. The temperature inside the reaction flask was lowered to 0℃~10℃. After the temperature stabilized, 125 g (1.05 mol) of thionyl chloride was slowly added dropwise. After all the materials were added, the temperature inside the reaction flask was maintained at 0℃~10℃ for 2 h. When the content of leaf alcohol was less than 0.5% by gas phase detection, the reaction was terminated. The reaction solution was slowly poured into 300 g of water for quenching. The mixture was separated, and then the water was back-extracted, washed with water, and the organic phase was dried. The organic phase was distilled under reduced pressure to obtain 102 g of 1-chloro-(Z)-3-hexene with a purity >97% and a yield of 86%.
[0015] In the first step of Example 1, the temperature was 15℃~25℃, the product purity was >97%, and the yield was 95%. In this step, the temperature was 0℃~10℃, the product purity was >97%, and the yield was 86%.
[0016] Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture with nitrogen three times, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. The reaction endpoint is reached when the 1-chloro-(Z)-3-hexene content is less than 1.0% as detected by gas phase analysis. After the reaction is complete, cool to -10℃. At 0℃, 11g (0.04mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -20℃ to -10℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -20℃ to -10℃ for 1 to 2 hours. The content of ethyl bromoacetate was <1% by gas phase detection. After the reaction was completed, the reaction solution was transferred in batches to ammonium chloride aqueous solution for quenching. After standing and separation, the upper organic phase was retained, and the aqueous phase was extracted with toluene. The organic phases were combined, washed with water, dried, and concentrated under reduced pressure to recover the solvent, and crude ethyl cis-5-octenate was obtained. The crude product was then subjected to reduced pressure distillation to obtain 46g of ethyl cis-5-octenate with a purity >97% and a yield of 32%.
[0017] In the second step of Example 1, the temperature was -10℃ to 0℃, the product purity was >97%, and the yield was 80%. In this step, the temperature was -20℃ to -10℃, the product purity was >97%, and the yield was 32%.
[0018] Step 3: Synthesis of cis-5-octen-1-ol 77 g (0.45 mol) of ethyl cis-5-octenate was added to a 1000 mL four-necked flask, followed by 300 g of toluene. The temperature inside the reaction flask was lowered to -10℃ to 0℃. After the temperature stabilized, 127 g (0.47 mol, 70 wt% toluene solution) of red aluminum toluene solution was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -10℃ to 0℃ for 1 to 2 hours. The content of ethyl cis-5-octenate was <0.5% by gas phase analysis. After the reaction was completed, the reaction solution was transferred in batches to dilute hydrochloric acid for quenching. After quenching, the mixture was allowed to stand and separated. The upper organic phase was retained. The organic phase was washed with water, dried, and concentrated to recover toluene, yielding crude cis-5-octen-1-ol. The crude product was then subjected to vacuum distillation to obtain 54 g of cis-5-octen-1-ol with a purity >97% and a yield of 92%.
[0019] In the third step of Example 1, the temperature was 0℃~10℃, the product purity was >97%, and the yield was 95%. In this step, the temperature was -10℃~0℃, the product purity was >97%, and the yield was 92%.
[0020] Comparative Example 2 Step 1: Synthesis of 1-chloro-(Z)-3-hexene 100 g (1.0 mol) of leaf alcohol was added to a 500 mL four-necked flask, followed by 300 g of dichloromethane and 3.6 g of N,N-dimethylformamide. The mixture was stirred for 10 min until homogeneous. The temperature inside the reaction flask was lowered to 30℃±5℃. After the temperature stabilized, 125 g (1.05 mol) of thionyl chloride was slowly added dropwise. After all the materials were added, the temperature inside the reaction flask was maintained at 30℃±5℃ for 2 h. The leaf alcohol content was found to be less than 0.5% by gas phase detection. The reaction was then terminated. The reaction solution was slowly poured into 300 g of water for quenching. The mixture was separated, and the water was back-extracted, washed with water, and the organic phase was dried. The organic phase was then distilled under reduced pressure to obtain 90 g of 1-chloro-(Z)-3-hexene with a purity >97% and a yield of 76%.
[0021] In the first step of Example 1, the temperature was 15℃~25℃, the product purity was >97%, and the yield was 95%. In this step, the temperature was 30℃±5℃, the product purity was >97%, and the yield was 76%.
[0022] Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture with nitrogen three times, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After the system is properly initiated (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. Gas phase detection shows that the 1-chloro-(Z)-3-hexene content is less than 1.0%, indicating the reaction is complete. At the endpoint, after the reaction was completed, the temperature was lowered to -10℃ to 0℃, and 11g (0.04mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at 0℃ to 10℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at 0℃ to 10℃ for 1 to 2 hours. The content of ethyl bromoacetate was detected by gas phase analysis as <1%. After the reaction was completed, the reaction solution was transferred in batches to ammonium chloride aqueous solution for quenching, allowed to stand and separate, and the aqueous phase was extracted with toluene. After washing with water, drying, and vacuum distillation, crude product was obtained. The crude product was then purified by vacuum distillation to obtain 29g of ethyl maleate (cis-5-octenate) with a purity >97% and a yield of 20%.
[0023] In the second step of Example 1, the temperature was -10℃ to 0℃, the product purity was >97%, and the yield was 80%. In this step, the temperature was 0℃ to 10℃, the product purity was >97%, and the yield was 20%.
[0024] Step 3: Synthesis of cis-5-octen-1-ol 77 g (0.45 mol) of ethyl cis-5-octenate was added to a 1000 mL four-necked flask, followed by 300 g of toluene. The temperature inside the reaction flask was lowered to 10-20 °C. After the temperature stabilized, 127 g (0.47 mol, 70 wt% toluene solution) of red aluminum toluene solution was slowly added dropwise. The temperature of the reaction system was controlled at 10-20 °C during the dropwise addition. After the dropwise addition was completed, the reaction was maintained at 10-20 °C for 1-2 hours. The content of ethyl cis-5-octenate was <0.5% by gas phase analysis. After the reaction was completed, the reaction solution was transferred in batches to dilute hydrochloric acid for quenching. After quenching, the mixture was allowed to stand and separated. The upper organic phase was retained. The organic phase was washed with water, dried, and concentrated to recover toluene, yielding crude cis-5-octen-1-ol. The crude product was then subjected to vacuum distillation to obtain 53 g of cis-5-octen-1-ol with a purity >97% and a yield of 92%.
[0025] In the third step of Example 1, the temperature was 0℃~10℃, the product purity was >97%, and the yield was 95%. In this step, the temperature was 10℃~20℃, the purity was >97%, and the yield was 92%.
[0026] Comparative Example 3 Step 1: Synthesis of 1-chloro-(Z)-3-hexene 100 g (1.0 mol) of leaf alcohol was added to a 500 mL four-necked flask, followed by 300 g of dichloromethane and 7.2 g of N,N-dimethylformamide. The mixture was stirred for 10 min until homogeneous. The temperature was then lowered to 15℃~25℃. After the temperature stabilized, 125 g (1.05 mol) of thionyl chloride was slowly added dropwise. After the addition was complete, the temperature in the reaction flask was maintained at 15℃~25℃ for 2 h. The leaf alcohol content was found to be less than 0.5% by gas phase analysis. The reaction was then terminated. The reaction solution was slowly poured into 300 g of water for quenching. The mixture was separated, and the aqueous phase was back-extracted with dichloromethane, the organic phase was washed with water, dried over anhydrous Mg2SO4, and distilled under reduced pressure to obtain 112 g of 1-chloro-(Z)-3-hexene with a purity >97% and a yield of 95%.
[0027] In the first step of Example 1, 3.6 g of N,N-dimethylformamide was used, with a product purity >97% and a yield of 95%. In this step, 7.2 g of N,N-dimethylformamide was used, with a product purity >97% and a yield of 95%. Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture with nitrogen three times, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. The reaction endpoint is reached when the 1-chloro-(Z)-3-hexene content is less than 1.0% as detected by gas chromatography. The temperature was lowered to -10℃ to 0℃, and 22g (0.08mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -10℃ to 0℃ for 1 to 2 hours. The content of ethyl bromoacetate was detected by gas phase analysis as <1%. After the reaction was completed, the reaction solution was transferred in batches to ammonium chloride aqueous solution for quenching. The organic phase was retained, and the aqueous phase was extracted with toluene. The organic phase was washed with water, dried, and distilled under reduced pressure to obtain crude ethyl cis-5-octenate. The crude product was then purified by reduced pressure distillation to obtain 75g of ethyl cis-5-octenate with a purity >97% and a yield of 52%.
[0028] In the second step of Example 1, 11g of cuprous iodide was used, with a product purity >97% and a yield of 80%. In this step, 22g of cuprous iodide was used, with a product purity >97% and a yield of 52%.
[0029] Step 3: Synthesis of cis-5-octen-1-ol 77 g (0.45 mol) of ethyl cis-5-octenate was added to a 1000 mL four-necked flask, followed by 300 g of toluene. The temperature inside the reaction flask was lowered to 0-10 °C. After the temperature stabilized, 515 g (0.90 mol, 25 wt% toluene solution of diisobutylaluminum hydride) was slowly added dropwise. The temperature of the reaction system was controlled at 0-10 °C during the dropwise addition. After the dropwise addition was completed, the reaction was maintained at 0-10 °C for 1-2 hours. The content of ethyl cis-5-octenate was <0.5% by gas phase analysis. After the reaction was completed, the reaction solution was transferred in batches to dilute hydrochloric acid for quenching. After quenching, the mixture was allowed to stand and separated, retaining the upper organic phase. The organic phase was washed with water, dried, and concentrated to recover toluene, yielding crude cis-5-octen-1-ol. The crude product was then subjected to vacuum distillation to obtain 54.5 g of cis-5-octen-1-ol with a purity >97% and a yield of 94%.
[0030] In the third step of Example 1, a red aluminum toluene solution was slowly added dropwise, resulting in a product purity > 97% and a yield of 95%. In this step, a diisobutylaluminum hydride toluene solution was slowly added dropwise, resulting in a product purity > 97% and a yield of 94%.
[0031] Comparative Example 4 Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture with nitrogen three times, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. The reaction endpoint is reached when the 1-chloro-(Z)-3-hexene content is less than 1.0% as detected by gas chromatography. The temperature was lowered to -10℃ to 0℃, and 2.2g (0.01mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -10℃ to 0℃ for 1 to 2 hours. The content of ethyl bromoacetate was detected by gas phase analysis and found to be <1%. After the reaction was completed, the reaction solution was transferred in batches to ammonium chloride aqueous solution for quenching. The organic phase was retained, and the aqueous phase was extracted with toluene. The organic phase was washed with water, dried, and distilled under reduced pressure to obtain crude ethyl cis-5-octenate. The crude product was then purified by reduced pressure distillation to obtain 46g of ethyl cis-5-octenate with a purity >97% and a yield of 32%.
[0032] In the second step of Example 1, 11g of cuprous iodide was used, with a product purity >97% and a yield of 80%. In this step, 2.2g of cuprous iodide was used, with a product purity >97% and a yield of 32%.
[0033] Comparative Example 5 Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture three times with nitrogen, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the temperature at 60℃~65℃. The reaction was carried out at 5℃ for 1-2 hours. The gas phase detection showed that the 1-chloro-(Z)-3-hexene content was less than 1.0%, which was the reaction endpoint. After the reaction was completed, the temperature was lowered to -10℃ to 0℃, and 6.1g (0.04mol) of cuprous bromide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was carried out at -10℃ to 0℃ for 1-2 hours. The gas phase detection showed that there was basically no reaction, and the product purity was <2%.
[0034] In the second step of Example 1, cuprous iodide was added in one step, resulting in a product purity >97% and a yield of 80%. In this step, cuprous bromide was added in one step, and gas phase detection showed almost no reaction, resulting in a product purity <2%.
[0035] Comparative Example 6 Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture three times with nitrogen, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the temperature at 60℃~ The reaction was carried out at 65℃ for 1-2 hours. The gas phase detection showed that the 1-chloro-(Z)-3-hexene content was less than 1.0%, which was the reaction endpoint. After the reaction was completed, the temperature was lowered to -10℃ to 0℃, and 11g (0.04mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the gas three times. After the temperature stabilized, 104g (0.84mol) of ethyl chloroacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was carried out at -10℃ to 0℃ for 1-2 hours. The gas phase detection showed that there was basically no reaction, and the product purity was <2%.
[0036] In the second step of Example 1, ethyl bromoacetate was added dropwise, resulting in a product purity >97% and a yield of 80%. In this step, ethyl chloroacetate was added dropwise, and gas phase detection showed virtually no reaction, resulting in a product purity <2%.
[0037] Comparative Example 7 Step 2: Synthesis of ethyl cis-5-octenate Add 300g of tetrahydrofuran to a 1000mL four-necked flask, start stirring, then add 20g of magnesium shavings (0.84mol) and 0.1g of iodine. Purge the mixture three times with nitrogen, maintaining nitrogen protection throughout the reaction. Heat to 60℃~65℃. When the system color changes from brown to grayish-white, add 5g of 1-chloro-(Z)-3-hexene (0.04mol). After normal initiation (the system color changes from grayish-white to black or the temperature rises significantly), add the remaining 95g of 1-chloro-(Z)-3-hexene (0.8mol). After the addition is complete, maintain the reaction at 60℃~65℃ for 1h~2h. The reaction endpoint is reached when the 1-chloro-(Z)-3-hexene content is less than 1.0% as determined by gas phase analysis. After the reaction was completed, the temperature was lowered to -10℃ to 0℃, and 11g (0.04mol) of cuprous iodide was added at once. After the addition was completed, nitrogen was used to purge the mixture three times. After the temperature stabilized, 153g (0.84mol) of ethyl bromoacetate was slowly added dropwise. The temperature of the reaction system was controlled at -10℃ to 0℃ during the dropwise addition. After the dropwise addition was completed, the reaction was kept at -10℃ to 0℃ for 1 to 2 hours. The content of ethyl bromoacetate was detected by gas phase analysis and found to be <1%. After the reaction was completed, the reaction solution was transferred in batches to dilute hydrochloric acid for quenching. The organic phase was retained, and the aqueous phase was extracted with toluene. The organic phase was washed with water, dried, and distilled under reduced pressure to obtain crude ethyl cis-5-octenate. The crude product was then purified by reduced pressure distillation to obtain 50g of ethyl cis-5-octenate with a purity >97% and a yield of 35%.
[0038] In the second step of Example 1, the reaction solution was quenched in batches in an aqueous ammonium chloride solution, resulting in a product purity > 97% and a yield of 80%. In this step, the reaction solution was quenched in batches in dilute hydrochloric acid, resulting in a product purity > 97% and a yield of 35%.
[0039] The above embodiments are only used to illustrate the technical concept and features of the present invention, and are not intended to be unique or to limit the present invention. Those skilled in the art should understand that various changes or equivalent substitutions made to the present invention without departing from its scope are all within the protection scope of the present invention.
Claims
1. A method for synthesizing cis-5-octen-1-ol, characterized in that, Includes the following steps: Step 1: Using leaf alcohol as the starting material, a substitution reaction is carried out with thionyl chloride to obtain 1-chloro-(Z)-3-hexene; Step 2: 1-Chloro-(Z)-3-hexene is reacted with magnesium shavings to obtain cis-3-hexene magnesium chloride Grignard reagent. The Grignard reagent is then reacted with ethyl bromoacetate under catalytic conditions to obtain ethyl cis-5-octenate. Step 3: Reduce ethyl cis-5-octenate with red aluminum to obtain cis-5-octen-1-ol.
2. The method for synthesizing cis-5-octen-1-ol according to claim 1, characterized in that, The first step includes: Dichloromethane, leaf alcohol, and N,N-dimethylformamide were mixed evenly. The mixture was cooled to 15℃~25℃, and thionyl chloride was added dropwise. The mixture was stirred for 2 hours. The reaction solution was quenched in ice water, separated, washed with water, dried, filtered with desiccant, and distilled under reduced pressure to obtain 1-chloro-(Z)-3-hexene.
3. The method for synthesizing cis-5-octen-1-ol according to claim 1, characterized in that, The second step includes: mixing tetrahydrofuran, magnesium shavings, and iodine, purging with nitrogen, heating to 60℃~65℃, adding a small amount of 1-chloro-(Z)-3-hexene dropwise, and continuing to add the remaining 1-chloro-(Z)-hexene dropwise after the system is initiated. The reaction is stirred at 60℃~65℃ for 2 hours. After the reaction is completed, the temperature is lowered to -10℃~0℃, cuprous iodide is added all at once, followed by ethyl bromoacetate. The reaction is stirred at -10℃~0℃ for 2 hours. After the reaction is completed, the reaction solution is slowly poured into an ammonium chloride aqueous solution for quenching, separated, washed with water, dried, filtered with desiccant, and distilled under reduced pressure. After reduced pressure distillation, ethyl maleate (cis-5-octenate) is obtained.
4. The method for synthesizing cis-5-octen-1-ol according to claim 1, characterized in that, The third step includes: mixing ethyl cis-5-octenate with toluene, cooling to 0℃~10℃, slowly adding red aluminum toluene solution, stirring the reaction at 0℃~10℃ for 2 hours, slowly pouring the reaction solution into ice water to quench it, separating the liquid, washing with water, drying, filtering the desiccant, vacuum distilling, and vacuum fractionation to obtain cis-5-octen-1-ol.