Preparation method of insect sex pheromone (8E, 10E)-dodecadiene-1-alcohol

Abstract

The invention relates to the field of preparation of insect sex pheromone, in particular to a preparation method of insect sex pheromone (8E, 10E)-dodecadiene-1-alcohol. The method comprises the following steps: in an N2 atmosphere, carrying out a reaction on p-toluenesulfonic acid propargyl ester and HML (zirconocene hydrogen chloride), under the action of Pd (Ph3P) 2Cl2 and R2AlH (2), carrying out a reaction with (E)-halogenated propylene (1) to prepare an intermediate (I), carrying out a reaction on the intermediate (I) and a Grignard reagent (3), and carrying out hydrolysis to prepare the insect sex pheromone (8E, 10E)-dodecadiene-1-alcohol. The method disclosed by the invention is mild in reaction condition, simple in post-treatment, environment-friendly, high in product yield, good in stereoselectivity and suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis of insect sex pheromones, specifically, to a method for preparing the insect sex pheromone (8E,10E)-dodecadien-1-ol. Background Technology

[0002] Insect sex pheromones are trace chemical substances secreted by insects that are received by individuals of the same species of the opposite sex, inducing certain reproductive behaviors in the mates. Utilizing insect sex pheromones for pest and disease control has become a practical and widely applied pest control technique. Currently, developed countries in Europe and America extensively use insect sex pheromones to control crop diseases, achieving the goals of ensuring quality and increasing yields, and promoting green agriculture.

[0003] (8E,10E)-dodecadien-1-ol is used to control the codling moth due to its high specificity, high efficiency, lack of pollution, non-harmful to beneficial insects, and absence of fruit residue. It is also used as a synergist for the sex pheromone of the pear fruit moth. However, its content in adult insects is extremely low, making extraction from insects for pest control impractical. Therefore, researching a simple and feasible chemical synthesis method for the codling moth pheromone has significant application value. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing the insect sex pheromone (8E, 10E)-dodecadien-1-ol, specifically including the following steps:

[0005] Where ML is Cp2ZrCl; R are each independently Et, Pr, Bu, i -Bu; X are independently Cl, Br, I; (a) Under N2 atmosphere, p-toluenesulfonic acid propyne ester and HML were added to dry THF and reacted at room temperature for 40-60 min. Then, THF solutions of (E)-halopropene (1), Pd(Ph3P)2Cl2 and R2AlH (2) were added sequentially and reacted at room temperature for 12-24 h. THF was evaporated under reduced pressure, n-hexane was added, the mixture was filtered to remove the catalyst, the catalyst was recovered and reused, the filtrate was concentrated, and purified by column chromatography to obtain intermediate (I). (b) Under a N2 atmosphere, intermediate (I) was added dropwise to dry THF at -5 to 0°C. After adding the THF solution, keep the reaction at room temperature for 1 hour, then react at room temperature for 3-4 hours. Add saturated NH4Cl solution to quench the reaction, distill off THF under reduced pressure, extract with n-hexane, dry with anhydrous Na2SO4, filter, and concentrate to obtain intermediate (II) crude product. (c) Add crude intermediate (II) to methanol, add water and acid, reflux for 3-4 h, distill off methanol, extract with n-hexane, dry with anhydrous Na2SO4, filter, concentrate, and distill under reduced pressure to obtain insect sex pheromone (8E,10E)-dodecadien-1-ol.

[0006] Further, in step (a), the molar ratio of p-toluenesulfonate propyne ester, HML, and (E)-halopropene (1) is 2-2.2:2-2.2:1; the molar ratio of (E)-haloalkene (1) to Pd(Ph3P)2Cl2 and R2AlH (2) is 1:0.05-0.06:0.1-0.12; in step (b), intermediate (I) and The molar ratio is 1:1-1.2; in step (c), the acid is... p -TsOH, with a mass fraction of 5%-10%.

[0007] Advantages of this invention: Compared with the prior art, this invention discloses a novel method for preparing the insect sex pheromone (8E, 10E)-dodecadien-1-ol. This method involves reacting p-toluenesulfonate propyne ester with HML (zirconium hydride) to selectively generate the (E)-active intermediate alkenylzirconium (… The reaction of Pd(Ph3P)2Cl2 with R2AlH(2) generates a catalyst Pd(Ph3P)4 in situ, which catalyzes the reaction of (E)-halopropylene (1) with the (E)-active intermediate alkenylzirconium, yielding intermediate (I) in high yield and with high selectivity. Intermediate (I) is then reacted with a Grignard reagent and followed by acid-catalyzed hydrolysis to obtain (8E,10E)-dodecadien-1-ol in high yield and with high purity. This preparation method features mild reaction conditions, recyclable catalyst, low preparation cost, and is environmentally friendly, making it suitable for industrial production. Detailed Implementation

[0008] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto. Example 1

[0009] Preparation of intermediate (I) Under a nitrogen atmosphere, 392.4 mg (2 mmol) of propyne p-toluenesulfonate and 515.7 mg (2 mmol) of HML (zirconium hydride) were added to 13 mL of dry THF and reacted at room temperature for 40 min. Then, 168 mg (1 mmol) of (E)-propenyl iodide (1), 35 mg (0.05 mmol) of Pd(Ph3P)2Cl2 and 8.6 mg (0.1 mmol) of Et2AlH in 2 mL of THF solution were added sequentially and reacted at room temperature for 12 h. The THF was then distilled off under reduced pressure, n-hexane was added, and the mixture was filtered to remove the catalyst. The catalyst was recovered and reused. The filtrate was concentrated and purified by column chromatography to obtain intermediate (I) with a yield of 91.0%. Example 2

[0010] Preparation of intermediate (I) Under a nitrogen atmosphere, 431.6 mg (2.2 mmol) of propyne p-toluenesulfonate and 567.3 mg (2.2 mmol) of HML (zirconium hydride) were added to 15 mL of dry THF and reacted at room temperature for 60 min. Then, 121 mg (1 mmol) of (E)-bromoalkene (1), 42 mg (0.06 mmol) of Pd(Ph3P)2Cl2 and 13.7 mg (0.12 mmol) of Pr2AlH in 3 mL of THF solution were added sequentially and reacted at room temperature for 24 h. Other operations were the same as in Example 1 to obtain intermediate (I) with a yield of 87.3%. Example 3

[0011] Preparation of intermediate (I) Under a nitrogen atmosphere, 412 mg (2.1 mmol) of propyne p-toluenesulfonate and 541.5 mg (2.1 mmol) of HML (zirconium chlorohydrin) were added to 13 mL of dry THF and reacted at room temperature for 50 min. Then, 168 mg (1 mmol) of (E)-propenyl iodide (1), 38.6 mg (0.055 mmol) of Pd(Ph3P)2Cl2 and 15.6 mg (0.11 mmol) of Pd(Ph3P)2Cl2 were added sequentially. i The intermediate (I) was prepared by reacting 2 mL of Bu2AlH THF solution at room temperature for 15 h, with other operations the same as in Example 1, with a yield of 94.6%. Example 4

[0012] Preparation of intermediate (I) Under a nitrogen atmosphere, 412 mg (2.1 mmol) of propyne p-toluenesulfonate and 541.5 mg (2.1 mmol) of HML (zirconium hydride) were added to 11 mL of dry THF and reacted at room temperature for 50 min. Then, 76.5 mg (1 mmol) of (E)-chloropropene (1), 38.6 mg (0.055 mmol) of Pd(Ph3P)2Cl2 and 15.6 mg (0.11 mmol) of Bu2AlH in 2 mL of THF solution were added sequentially and reacted at room temperature for 24 h. Other operations were the same as in Example 1 to obtain intermediate (I) with a yield of 78.3%. Example 5

[0013] Preparation of (8E,10E)-dodecadien-1-ol Add 1.81 g (10 mmol) Br(CH2)6OH and 1.01 g (12 mmol) 2,3-dihydropyran and 10% by mass of [unspecified ingredient] to 15 mL of ethyl acetate. p -TsOH, reacted at room temperature for 12 h, concentrated, purified, and then obtained. ; Add 264 mg (11 mmol) of magnesium powder and one iodine tablet to 25 mL of dry THF, and then add 2.65 g (10 mmol) dropwise. / 5mL of dry THF solution, react for 1 hour, to prepare the... Prepare a THF solution for later use; Under a nitrogen atmosphere, 252.3 mg (1 mmol) of intermediate (I) was added to 7 mL of dry THF, and 289.5 mg (1 mmol) was added dropwise at -5 to 0 °C. The THF solution was added dropwise, and the reaction was maintained at this temperature for 1 hour, followed by 3 hours at room temperature. The reaction was quenched by adding saturated NH4Cl solution, and the THF was evaporated under reduced pressure. The mixture was extracted with n-hexane, dried over anhydrous Na2SO4, filtered, and concentrated to obtain crude intermediate (II). The crude intermediate (II) was then added to 70 mL of methanol, followed by 7 mL of water and 10% (w / w) of [unspecified ingredient]. p -TsOH, reflux for 3 h, distill off methanol, extract with n-hexane, dry with anhydrous Na2SO4, filter, concentrate, and distill under reduced pressure to obtain the insect sex pheromone (8E,10E)-dodecadien-1-ol, with a yield of 81.1% and a purity of 98.3%. Example 6

[0014] Preparation of (8E,10E)-dodecadien-1-ol Under a nitrogen atmosphere, 252.3 mg (1 mmol) of intermediate (I) was added to 8 mL of dry THF, and 347.4 mg (1.2 mmol) was added dropwise at -5 to 0 °C. The THF solution was added dropwise, and the reaction was maintained at this temperature for 1 hour, followed by 4 hours at room temperature. The reaction was quenched by adding saturated NH4Cl solution, and the THF was evaporated under reduced pressure. The mixture was extracted with n-hexane, dried over anhydrous Na2SO4, filtered, and concentrated to obtain crude intermediate (II). The crude intermediate (II) was then added to 60 mL of methanol, followed by 8 mL of water and 5% (w / w) of [unspecified ingredient]. p -TsOH, reflux for 4 h, and perform other operations as in Example 5 to obtain the insect sex pheromone (8E,10E)-dodecadien-1-ol with a yield of 81.5% and a purity of 98.5%.

Claims

1. A method for preparing the insect sex pheromone (8E,10E)-dodecadien-1-ol, characterized in that, The preparation method includes the following steps: ， Where ML is Cp2ZrCl; R are each independently Et, Pr, Bu, i -Bu; X are independently Cl, Br, I; (a) Under N2 atmosphere, p-toluenesulfonic acid propyne ester and HML were added to dry THF and reacted at room temperature for 40-60 min. Then, THF solutions of (E)-halopropene (1), Pd(Ph3P)2Cl2 and R2AlH (2) were slowly added in sequence and reacted at room temperature for 12-24 h. THF was evaporated under reduced pressure, n-hexane was added, the mixture was filtered to remove the catalyst, the catalyst was recovered and reused, the filtrate was concentrated, and purified by column chromatography to obtain intermediate (I). (b) Under a N2 atmosphere, intermediate (I) was added dropwise to dry THF at -5 to 0°C. After adding the THF solution, keep the reaction at room temperature for 1 hour, then react at room temperature for 3-4 hours. Add saturated NH4Cl solution to quench the reaction, distill off THF under reduced pressure, extract with n-hexane, dry with anhydrous Na2SO4, filter, concentrate, and obtain crude intermediate (II). (c) Add crude intermediate (II) to methanol, add water and acid, reflux for 3-4 h, distill off methanol, extract with n-hexane, dry with anhydrous Na2SO4, filter, concentrate, and distill under reduced pressure to obtain insect sex pheromone (8E,10E)-dodecadien-1-ol.

2. The method for preparing the insect sex pheromone (8E,10E)-dodecadien-1-ol according to claim 1, characterized in that, In step (a), the molar ratio of propyne p-toluenesulfonate, HML, and (E)-halopropene (1) is 2-2.2:2-2.2:1; the molar ratio of (E)-halopropene (1) to Pd(Ph3P)2Cl2 and R2AlH (2) is 1:0.05-0.06:0.1-0.12; in step (b), intermediate (I) and The molar ratio is 1:1-1.2; in step (c), the acid is... p -TsOH, with a mass fraction of 5%-10%.

Images