A method for synthesizing (2e,4z)-2,4-decadienoic acid ethyl ester

Abstract

The application discloses a synthesis method of (2E,4Z)-2,4-decadienoic acid ethyl ester, and belongs to the technical field of perfume synthesis. The method comprises the following steps: 3-octyn-1-ol is subjected to the oxidation of Akira Yoshide to obtain 2-octynal; after the aldol condensation and decarboxylation reaction of 2-octynal and malonic acid, E-dec-2-en-4-ynoic acid is obtained; the esterification reaction of the obtained carboxylic acid is carried out to obtain E-dec-2-en-4-ynoic acid ethyl ester; and the enynoic acid ester is subjected to cis-reduction to obtain (2E,4Z)-2,4-decadienoic acid ethyl ester. The synthesis method has the advantages of simpler operation, less waste, high selectivity, guaranteed yield and product quality, and is more suitable for industrialized scale production.

Description

Technical Field

[0001] This invention belongs to the field of fragrance synthesis technology, specifically relating to a method for synthesizing (2E,4Z)-2,4-decadienoic acid ethyl ester. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Ethyl (2E,4Z)-2,4-decadienoic acid (CAS: 3025-30-7) is a colorless to pale yellow liquid organic compound with a sharp, fruity aroma reminiscent of pears, grass, and apples. It is naturally found in fruits such as apples, pineapples, and pears. Due to its unique aroma characteristics, ethyl (2E,4Z)-2,4-decadienoic acid is an indispensable flavoring ingredient in the food, cosmetics, daily chemical products, and perfume industries.

[0004] Existing technologies use 3,3-dimethoxy-1-propyne and halopentane as raw materials, successively undergoing substitution, hydrolysis, and hydrogenation reactions to produce ethyl trans-2-cis-4-decadienoate. This involves the Wittig reaction of 2-octanal with triethyl phosphonoacetate in the presence of a basic substance B, such as butyllithium, phenyllithium, sodium hydride, sodium hydroxide, sodium amide, or sodium ethoxide. The use of triethyl phosphonoacetate not only increases production costs but also violates atom economy principles; the generation of organophosphorus byproducts further complicates post-processing. Another existing technology uses hexanal as a starting material, undergoing three chemical transformations to prepare the key intermediate 1-bromoheptene, which then undergoes a coupling reaction with ethyl acrylate under a metal catalyst to obtain ethyl (E,Z)-2,4-decadienoate. The use of elemental bromine has the following drawbacks: the high toxicity and volatility of elemental bromine pose safety hazards to the production process; due to the active chemical properties of the dibromo intermediate, it is prone to side reactions such as elimination and substitution; and all bromine atoms in the reaction are not retained in the final product, resulting in low atom utilization.

[0005] The existing technology for preparing (2E,4Z)-2,4-decadienoic acid ethyl ester still has the following main problems: 1. The use of equivalent or excess manganese oxide or aluminum oxide and other metal oxides results in a lot of solid waste generated in the post-processing; 2. The formation of active intermediates such as allenes makes it easy to generate more by-products in the reaction process; 3. The selectivity of cis-trans isomers is poor, making it difficult to obtain high-purity (2E,4Z)-2,4-decadienoic acid ethyl ester products. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a method for synthesizing (2E,4Z)-2,4-decadienoic acid ethyl ester. This method has the advantages of simpler operation, less waste, and high selectivity, with guaranteed yield and product quality, making it more suitable for industrial-scale production.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] A method for synthesizing ethyl (2E,4Z)-2,4-decadienoic acid, comprising the following steps:

[0009] Step 1: 2-Octyne-1-ol undergoes oxidative oxidation with methanoyl to yield 2-octynealdehyde;

[0010] Step 2: In the presence of an alkaline reagent, 2-octynealdehyde and malonic acid undergo aldol condensation and decarboxylation to yield E-dec-2-ene-4-acetic acid.

[0011] Step 3: The obtained carboxylic acid undergoes an esterification reaction to give ethyl E-dec-2-ene-4-acetylacetic acid;

[0012] Step 4: The ethynate is reduced by cis to obtain ethyl (2E,4Z)-2,4-decadienoate.

[0013] The synthetic route provided by this invention utilizes the methimazole oxidation reaction to obtain a conjugated alkynyl aldehyde. This aldehyde structure is more stable, thereby achieving a higher yield of the final product.

[0014] Preferably, in step 1, during the oxidation reaction of methanotroph, the molar ratio of the catalyst to 2-octyne-1-ol is 3:8~12; the catalyst used is a combination of ferric nitrate or its hydrate, piperidine nitroxide radicals, and sodium chloride; the molar ratio of ferric nitrate or its hydrate, piperidine nitroxide radicals, and sodium chloride is 0.8~1.2:0.8~1.2:0.8~1.2.

[0015] In the embodiments of the present invention, a comparison of catalysts was conducted, and it was found that when ferric nitrate was replaced with copper nitrate, the yield decreased slightly, while a higher yield was obtained based on ferric nitrate.

[0016] Preferably, in step 1, during the oxidation reaction of methanosome, the nitroxide radical of piperidine used in the catalyst is 4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide radical or 2,2,6,6-tetramethylpiperidine nitroxide radical.

[0017] Preferably, in step 2, the aldol condensation and decarboxylation reaction of 2-octynealdehyde and malonic acid is carried out by a combination of triethylamine and pyridine.

[0018] Preferably, step 2 further includes, after the reaction, diluting with dichloromethane, then slowly adding hydrochloric acid aqueous solution while stirring, extracting and separating, and removing the organic solvent by vacuum distillation to obtain E-dec-2-ene-4-acetylic acid.

[0019] Considering the issues of solvent post-processing and residue, the present invention preferably uses dichloromethane to dilute the reaction products.

[0020] Preferably, in step 3, the catalyst used in the esterification reaction is concentrated sulfuric acid.

[0021] Preferably, in step 3, the E-dec-2-ene-4-acetylic acid obtained in step 2 is mixed with ethanol, concentrated sulfuric acid is added dropwise under stirring, the mixture is heated to reflux reaction, cooled to room temperature, and some ethanol is removed by vacuum distillation. The mixture is then diluted with dichloromethane, deionized water is added for extraction and separation, and the organic solvent is removed by vacuum distillation to obtain ethyl E-dec-2-ene-4-acetylic acid.

[0022] Preferably, in step 4, the cis-reduction of the alkenyl ester is carried out using a Lindlar catalyst. The reaction takes place in the presence of hydrogen.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] 1. This invention provides the following synthesis method: 2-Octyne-1-ol undergoes oxidative oxidation with methanoate to obtain 2-octynealdehyde; 2-octynealdehyde and malonic acid undergo aldol condensation and decarboxylation to obtain E-dec-2-en-4-alkynic acid; the obtained carboxylic acid undergoes esterification to obtain ethyl E-dec-2-en-4-alkynic acid; the alkynic acid ester undergoes cis-reduction to obtain ethyl (2E,4Z)-2,4-decadienoic acid. This method overcomes the problem of poor selectivity of cis-trans isomers in the prior art. Based on this method, high-purity ethyl (2E,4Z)-2,4-decadienoic acid can be obtained, with a product purity of up to 96%.

[0025] 2. The reaction process provided by this invention does not use alkaline catalysts such as sodium ethoxide, but uses malonic acid and triethylamine or pyridine to reduce the solid waste generated in the post-processing.

[0026] 3. The method of the present invention utilizes the methimazole oxidation reaction to obtain a more stable conjugated alkynyl aldehyde, thereby reducing the generation of by-products and improving the product yield. Attached Figure Description

[0027] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0028] Figure 1This is the 1H NMR spectrum of (2E,4Z)-2,4-decadienoic acid ethyl ester prepared in Example 1 of this invention;

[0029] Figure 2 This is the synthetic route for (2E,4Z)-2,4-decadienoic acid ethyl ester described in this invention. Detailed Implementation

[0030] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0031] In embodiments of the present invention, a method for synthesizing (2E,4Z)-2,4-decadienoic acid ethyl ester is provided, the synthetic route being as follows: Figure 2 As shown, it includes the following steps:

[0032] Step 1: 2-Octyne-1-ol undergoes oxidative oxidation with methanoyl to yield 2-octynealdehyde;

[0033] Step 2: In the presence of an alkaline reagent, 2-octynealdehyde and malonic acid undergo aldol condensation and decarboxylation to yield E-dec-2-ene-4-acetic acid.

[0034] Step 3: The carboxylic acid obtained in Step 2 undergoes an esterification reaction to give ethyl E-dec-2-ene-4-acetylacetic acid;

[0035] Step 4: The ethynate is reduced by cis to obtain ethyl (2E,4Z)-2,4-decadienoate.

[0036] In some embodiments, in the oxidative reaction of methanotroph in step 1, the molar ratio of the catalyst to 2-octyne-1-ol is 3:8~12; furthermore, the catalyst used is a combination of ferric nitrate or its hydrate, piperidine nitroxide radicals and sodium chloride; wherein the molar ratio of ferric nitrate or its hydrate, piperidine nitroxide radicals and sodium chloride is 0.8~1.2:0.8~1.2:0.8~1.2.

[0037] In some embodiments, the catalyst used in the oxidative reaction of methanoate in step 1 is a combination of ferric nitrate nonahydrate, 4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide radical (4-OH-TEMPO), and sodium chloride, or a combination of ferric nitrate nonahydrate, 2,2,6,6-tetramethylpiperidine nitroxide radical (TEMPO), and sodium chloride. More preferably, a combination of ferric nitrate nonahydrate, 4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide radical, and sodium chloride is used.

[0038] In some embodiments, in step 2, the aldol condensation and decarboxylation reaction of 2-octynealdehyde and malonic acid is carried out by a combination of triethylamine and pyridine.

[0039] In some embodiments, in step 2, the molar ratio of 2-octynaldehyde, malonic acid, and triethylamine is 1:1:1 to 1.5.

[0040] In some embodiments, the reaction temperature in step 2 is 70℃±5℃.

[0041] It also includes diluting with dichloromethane after the reaction, then slowly adding hydrochloric acid aqueous solution while stirring, extracting and separating, and removing the organic solvent by vacuum distillation to obtain E-dec-2-ene-4-acetylic acid.

[0042] Preferably, in step 3, the catalyst used in the esterification reaction is concentrated sulfuric acid.

[0043] In some embodiments, the E-dec-2-ene-4-acetylic acid obtained in step 2 is mixed with ethanol, and concentrated sulfuric acid is added dropwise under stirring. The mixture is heated to reflux and reacted. After cooling to room temperature, some ethanol is removed by vacuum distillation. The mixture is then diluted with dichloromethane, and deionized water is added for extraction and separation. The organic solvent is removed by vacuum distillation to obtain ethyl E-dec-2-ene-4-acetylic acid.

[0044] In some embodiments, in step 4, the cis-reduction of the ethynate is carried out using a Lindlar catalyst. The reaction is conducted in the presence of hydrogen. The amount of Lindlar catalyst added is 5 wt% to 10 wt% of E-dec-2-en-4-ethynate ethyl ester. In a more preferred embodiment, ethanol is used as the solvent in step 4, and the yield is higher than that of methanol. It is speculated that the core reason for this is the different adsorption competition of different solvents on the active sites of the catalyst and their different effects on the stability of the reaction intermediates, or the yield fluctuation caused by the mass transfer efficiency due to the difference in solvent polarity.

[0045] In steps 1, 3, and 4, the reaction temperature is room temperature, typically 25℃±5℃.

[0046] The purity of (2E,4Z)-2,4-decadienoic acid ethyl ester was determined by gas chromatography.

[0047] Column: DB-5 (30 m × 0.53 mm × 1.50 μm);

[0048] Conditions: Initial temperature 80℃, hold for 3 min; heating rate 15℃ / min, final temperature 260℃, hold for 10 min;

[0049] Inlet temperature: 270℃, Detector temperature: 280℃;

[0050] Detector: FID;

[0051] Carrier gas: Nitrogen;

[0052] Column flow rate: 3 ml / min;

[0053] Flow split ratio: 20:1;

[0054] Hydrogen flow rate: 40 ml / min;

[0055] Airflow rate: 350 ml / min;

[0056] Follow-through air: 25 ml / min.

[0057] The present invention will be further described below with reference to specific embodiments.

[0058] Example 1

[0059] The reaction process is shown in the following reaction equation:

[0060]

[0061] Under an oxygen atmosphere, Fe(NO3)3·9H2O (4 g, 10 mmol), 4-OH-TEMPO (1.7 g, 10 mmol), NaCl (0.58 g, 10 mmol), 2-octyne-1-ol (12.6 g, 100 mmol), and dichloromethane (300 mL) were added sequentially to the reaction flask. The mixture was stirred at room temperature for 24 hours until the reaction was complete. The organic solvent was removed by vacuum distillation, and the crude product was separated by column chromatography to obtain 10.7 g of 2-octynealdehyde, with a yield of 86%.

[0062] 2-Octynaldehyde (1.2 g, 10 mmol), malonic acid (1.0 g, 10 mmol), and triethylamine (1.2 g, 12 mmol) were added sequentially to the reaction flask. The mixture was heated to 70℃±5℃ and reacted for 10 hours. After cooling to room temperature, 50 mL of dichloromethane was added for dilution. Then, 15 mL of 0.5 M dilute hydrochloric acid aqueous solution was slowly added and stirred for 10 minutes. The mixture was extracted and separated, and the organic solvent was removed by vacuum distillation to obtain 1.3 g of E-dec-2-en-4-ynetic acid, with a yield of 78%.

[0063] E-dec-2-ene-4-alkynic acid (1.7 g, 10 mmol) and ethanol (20 mL) were added to the reaction flask. Under stirring, 2 drops of concentrated sulfuric acid were added dropwise, and the mixture was heated to reflux for 12 hours. After cooling to room temperature, some ethanol was removed by vacuum distillation. The mixture was then diluted with dichloromethane, and deionized water was added for extraction and separation. The organic solvent was removed by vacuum distillation to obtain 1.7 g of ethyl E-dec-2-ene-4-alkynic acid, with a yield of 87%.

[0064] Ethyl E-dec-2-ene-4-acetylacetic acid (1.9 g, 10 mmol), ethanol (30 mL), and Lindlar catalyst (95 mg, 5 wt%) were added sequentially to the reaction flask. The reaction was then carried out at room temperature for 14 hours in the presence of hydrogen at 1 atm. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. Column chromatography was used to obtain 1.6 g of (2E,4Z)-2,4-decadienoic acid ethyl ester, with a yield of 82% and a purity of 96%.

[0065] The 1H NMR spectrum of the product (2E,4Z)-2,4-decadienoic acid ethyl ester is as follows: Figure 1 As shown, ¹H NMR (500 MHz, CDCl₃) δ 7.61 (ddd, J = 15.2, 11.7, 1.0 Hz, 1H), 6.15–6.09 (m, 1H), 5.92–5.79 (m, 2H), 4.24–4.18 (m, 2H), 2.35–2.25 (m, 2H), 1.46–1.39 (m, 2H), 1.34–1.27 (m, 7H), 0.89 (t, J = 7.0 Hz, 3H).

[0066] Comparative Example 1:

[0067] The catalyst ratio in the first step of Example 1 was reduced from 10 mmol to 5 mmol, and the catalysts were Fe(NO3)3·9H2O (2 g, 5 mmol), 4-OH-TEMPO (0.85 g, 5 mmol), NaCl (0.29 g, 5 mmol), 2-octyne-1-ol (12.6 g, 100 mmol) and dichloromethane (300 mL) to obtain 9.1 g of 2-octynealdehyde, with a yield of 73%.

[0068] Comparative Example 2

[0069] The catalyst in the first step of Example 1 above was replaced with Cu(NO3)3·3H2O instead of Fe(NO3)3·9H2O. The catalysts were Cu(NO3)3·3H2O (1.4 g, 10 mmol), 4-OH-TEMPO (1.7 g, 10 mmol), NaCl (0.58 g, 10 mmol), 2-octyne-1-ol (12.6 g, 100.0 mmol), and dichloromethane (300 mL), yielding 9.8 g of 2-octynealdehyde with a yield of 79%.

[0070] Example 2:

[0071]

[0072] Under an oxygen atmosphere, Fe(NO3)3·9H2O (4 g, 10 mmol), TEMPO (1.6 g, 10 mmol), NaCl (0.58 g, 10 mmol), 2-octyne-1-ol (12.6 g, 100 mmol) and dichloromethane (300 mL) were added sequentially to the reaction flask. The mixture was stirred at room temperature for 24 hours until the reaction was complete. The organic solvent was removed by vacuum distillation, and the crude product was separated by column chromatography to obtain 10.0 g of 2-octynealdehyde, with a yield of 81%.

[0073] 2-Octynaldehyde (1.2 g, 10 mmol), malonic acid (1.0 g, 10 mmol), and triethylamine (1.0 g, 10 mmol) were added sequentially to the reaction flask. The mixture was heated to 70℃±5℃ and reacted for 10 hours. After cooling to room temperature, the mixture was diluted with dichloromethane (50 mL), and then 0.5 M dilute hydrochloric acid aqueous solution (15 mL) was slowly added. The mixture was stirred for 10 minutes, extracted, and the organic solvent was removed by vacuum distillation to obtain 1.1 g of E-dec-2-en-4-ynetic acid, with a yield of 66%.

[0074] E-dec-2-ene-4-alkynic acid (1.7 g, 10 mmol) and ethanol (20 mL) were added to the reaction flask. Under stirring, 2 drops of concentrated sulfuric acid were added dropwise, and the mixture was heated to reflux for 12 hours. After cooling to room temperature, some ethanol was removed by vacuum distillation. The mixture was then diluted with dichloromethane, and deionized water was added for extraction and separation. The organic solvent was removed by vacuum distillation to obtain 1.7 g of ethyl E-dec-2-ene-4-alkynic acid, with a yield of 87%.

[0075] Ethyl E-dec-2-ene-4-acetylacetic acid (1.9 g, 10 mmol), ethanol (30 mL), and Lindlar catalyst (190 mg, 10 wt%) were added sequentially to the reaction flask. The reaction was then carried out at room temperature for 14 hours in the presence of hydrogen at 1 atm. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. Column chromatography was used to obtain 1.6 g of ethyl (2E,4Z)-2,4-decadienoic acid, with a yield of 82% and a purity of 96%.

[0076] Example 3:

[0077]

[0078] Under an oxygen atmosphere, Fe(NO3)3·9H2O (4 g, 10 mmol), 4-OH-TEMPO (1.7 g, 10 mmol), NaCl (0.58 g, 10 mmol), 2-octyne-1-ol (12.6 g, 100 mmol), and dichloroethane (300 mL) were added sequentially to the reaction flask. The mixture was stirred at room temperature for 24 hours until the reaction was complete. The organic solvent was removed by vacuum distillation, and the crude product was separated by column chromatography to obtain 10.3 g of 2-octynealdehyde, with a yield of 83%.

[0079] 2-Octynaldehyde (1.2 g, 10 mmol), malonic acid (1.0 g, 10 mmol), and triethylamine (1.5 g, 15 mmol) were added sequentially to the reaction flask. The mixture was heated to 70℃±5℃ and reacted for 10 hours. After cooling to room temperature, the mixture was diluted with dichloromethane (50 mL), and then 0.5 M dilute hydrochloric acid aqueous solution (15 mL) was slowly added. The mixture was stirred for 10 minutes, extracted, and the organic solvent was removed by vacuum distillation to obtain 1.2 g of E-dec-2-en-4-ynetic acid, with a yield of 72%.

[0080] E-dec-2-ene-4-alkynic acid (1.7 g, 10 mmol) and ethanol (20 mL) were added to the reaction flask. Under stirring, 2 drops of concentrated sulfuric acid were added dropwise, and the mixture was heated to reflux for 12 hours. After cooling to room temperature, some ethanol was removed by vacuum distillation. The mixture was then diluted with dichloromethane, and deionized water was added for extraction and separation. The organic solvent was removed by vacuum distillation to obtain 1.7 g of ethyl E-dec-2-ene-4-alkynic acid, with a yield of 87%.

[0081] Ethyl E-dec-2-ene-4-acetylacetic acid (1.9 g, 10 mmol), methanol (30 mL), and Lindlar catalyst (95 mg, 5 wt%) were added sequentially to the reaction flask. The reaction was then carried out at room temperature for 14 hours in the presence of hydrogen at 1 atm. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. Column chromatography was used to obtain 1.5 g of (2E,4Z)-2,4-decadienoic acid ethyl ester, with a yield of 76% and a purity of 95%.

[0082] Example 4:

[0083]

[0084] Under an oxygen atmosphere, Fe(NO3)3·9H2O (4 g, 10 mmol), 4-OH-TEMPO (1.7 g, 10 mmol), NaCl (0.58 g, 10 mmol), 2-octyne-1-ol (12.6 g, 100 mmol), and dichloromethane (300 mL) were added sequentially to the reaction flask. The mixture was stirred at room temperature for 24 hours until the reaction was complete. The organic solvent was removed by vacuum distillation, and the crude product was separated by column chromatography to obtain 10.7 g of 2-octynealdehyde, with a yield of 86%.

[0085] 2-Octynaldehyde (1.2 g, 10 mmol), malonic acid (1.0 g, 10 mmol), and pyridine (0.9 g, 11 mmol) were added sequentially to a reaction flask. The mixture was heated to 70℃±5℃ and reacted for 10 hours. After cooling to room temperature, 50 mL of dichloromethane was added for dilution. Then, 15 mL of 0.5 M dilute hydrochloric acid aqueous solution was slowly added and stirred for 10 minutes. The mixture was extracted and separated, and the organic solvent was removed by vacuum distillation to obtain 1.0 g of E-dec-2-en-4-ynetic acid, with a yield of 60%.

[0086] E-dec-2-ene-4-alkynic acid (1.7 g, 10 mmol) and ethanol (20 mL) were added to the reaction flask. Under stirring, 5 drops of concentrated sulfuric acid were added dropwise, and the mixture was heated to reflux for 12 hours. After cooling to room temperature, some ethanol was removed by vacuum distillation. The mixture was then diluted with dichloromethane, and deionized water was added for extraction and separation. The organic solvent was removed by vacuum distillation to obtain 1.6 g of ethyl E-dec-2-ene-4-alkynic acid, with a yield of 82%.

[0087] Ethyl E-dec-2-ene-4-acetylacetic acid (1.9 g, 10 mmol), ethanol (30 mL), and Lindlar catalyst (95 mg, 3 wt%) were added sequentially to the reaction flask. The reaction was then carried out at room temperature for 14 hours in the presence of hydrogen at 1 atm. After the reaction was completed, the mixture was filtered, and the solvent was removed by vacuum distillation. Column chromatography was used to separate 1.5 g of (2E,4Z)-2,4-decadienoic acid ethyl ester, with a yield of 76% and a purity of 94%.

[0088] Comparative Example 3

[0089] The method for synthesizing ethyl (2E,4Z)-2,4-decadienoic acid was reported in the reference (Org. Synth.1988,66, 22,DOI: 10.15227 / orgsyn.066.0022), and its preparation method was replicated.

[0090]

[0091] Starting with 1-octyne-3-ol, it reacts with triethyl orthoacetate to obtain ethyl 3,4-decadienoate. Then, under the action of alkaline alumina at 200°C, a rearrangement reaction occurs to obtain (2E,4Z)-2,4-decadienoate ethyl ester with a yield of 67% and a purity of 90%.

[0092] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for the synthesis of (2E,4Z)-2,4-decadienoic acid ethyl ester, characterized in that, Comprising the following steps: Step 1, 2-octyn-1-ol undergoes a shibamitsu oxidation to obtain 2-octynaldehyde; Step 2, after the aldol condensation and decarboxylation of 2-octynaldehyde and malonic acid in the presence of a base reagent, E-dec-2-ene-4-ynoic acid is obtained; Step 3, the esterification of the obtained carboxylic acid obtains E-dec-2-ene-4-ynoic acid ethyl ester; Step 4, the cis-reduction of the ene-yne ester obtains (2E, 4Z)-2, 4-decadienoic acid ethyl ester; In step 1, in the shibamitsu oxidation reaction, the molar ratio of the catalyst to 2-octyn-1-ol is 3:8~12; the catalyst used is a combination of ferric nitrate or its hydrate, a piperidine nitroxide radical and sodium chloride; the molar ratio of ferric nitrate or its hydrate, a piperidine nitroxide radical and sodium chloride is 0.8~1.2:0.8~1.2:0.8~1.2; In step 2, in the aldol condensation and decarboxylation of 2-octynaldehyde and malonic acid, the base used is a combination of one or both of triethylamine and pyridine; In step 4, in the cis-reduction of the ene-yne ester, the catalyst used is Lindlar catalyst; In step 1, the reaction is carried out in an oxygen atmosphere; in step 4, the reaction is carried out in the presence of hydrogen.

2. The process for the synthesis of (2E,4Z)-2,4-decadienoic acid ethyl ester according to claim 1, characterized in that, In step 1, in the shibamitsu oxidation reaction, the piperidine nitroxide radical in the catalyst used is 4-hydroxy-2, 2, 6, 6-tetramethylpiperidine nitroxide radical or 2, 2, 6, 6-tetramethylpiperidine nitroxide radical.

3. The process for the synthesis of (2E,4Z)-2,4-decadienoic acid ethyl ester according to claim 1, characterized in that, In step 2, after the reaction, dichloromethane is added for dilution, then hydrochloric acid aqueous solution is added for stirring, extraction separation, and removal of organic solvents by reduced pressure distillation to obtain E-dec-2-ene-4-ynoic acid.

4. The process for the synthesis of (2E,4Z)-2,4-decadienoic acid ethyl ester according to claim 1, characterized in that, In step 3, in the esterification reaction, the catalyst used is concentrated sulfuric acid. 5.The method of synthesizing (2E, 4Z) -2, 4-decadienoic acid ethyl ester according to claim 1, characterized in that, In step 3, the E-dec-2-ene-4-ynoic acid obtained in step 2 is mixed with ethanol, and under stirring, concentrated sulfuric acid is added dropwise, the temperature is raised to reflux, the temperature is lowered to room temperature, part of the ethanol is removed by reduced pressure distillation, then diluted with dichloromethane, added with deionized water for extraction separation, and the organic solvents are removed by reduced pressure distillation to obtain E-dec-2-ene-4-ynoic acid ethyl ester. 6.The method of synthesizing (2E, 4Z) -2, 4-decadienoic acid ethyl ester according to claim 1, characterized in that, The reaction temperature of step 1, step 3 and step 4 is 25℃±5℃; the reaction temperature of step 2 is 70℃±5℃.

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