A method for synthesizing a conjugated diene amide of all (e) configuration

Abstract

The application discloses a synthesis method of a conjugated diene amide with a full (E) configuration, and belongs to the technical field of conjugated diene amide synthesis. The application realizes the conversion of an unsaturated aldehyde into a conjugated diene carboxylic acid ester by keeping the double bond configuration of the (E)-unsaturated aldehyde as a raw material, the double bond migration of a phosphoryl intermediate is used, the configuration isomerization in the traditional method is avoided, the product configuration is single, continuous reaction reduces separation loss, the total yield is about 20% higher than that of the prior art, the reaction condition is mild, and the method is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of conjugated diene amide synthesis technology, and specifically to a method for synthesizing a fully (E)-configured conjugated diene amide. Background Technology

[0002] Wallwort alkaloids are conjugated diene amides, and are important natural product analogs with anti-inflammatory, insecticidal, and other biological activities. The traditional synthetic methods for conjugated diene amides mainly involve the direct amidation reaction of unsaturated carboxylic acids with amines.

[0003] Traditional synthetic methods for conjugated diene amides suffer from low reaction selectivity, numerous side reactions, and complex post-processing. The double bonds of unsaturated carboxylic acids (e.g., 2E, 4E configurations) readily undergo cis-trans isomerization during condensation reactions, leading to mixed product configurations and low reaction selectivity. In direct amidation, carboxylic acids are prone to self-condensation to form anhydride byproducts or excessive reaction with amines to generate polysubstituted amides, resulting in a large number of byproducts. The use of condensing agents during the reaction generates urea byproducts, requiring multiple column chromatography separations and complex post-processing, thus reducing production efficiency.

[0004] A prior art synthetic method is disclosed, specifically a three-step process: (E)-oct-2-enal → (E)-oct-2-enoic acid (Jones' reagent oxidation) → (E)-oct-2-enoyl chloride (SOCl2 chlorination) → isobutylamide. In this reaction, the strongly acidic environment during Jones' reagent oxidation induces cis-trans isomerism of the double bond, with the (Z)-configuration accounting for 15%–20% of the product, resulting in severe configurational isomerization. Furthermore, the aldehyde group is easily over-oxidized to ketones or carboxylic acid derivatives during the oxidation step, leading to numerous byproducts. The cumulative product loss during the multi-step separation process results in a low overall yield of only 40%–45%. Summary of the Invention

[0005] This invention provides a method for synthesizing fully (E)-configured conjugated diene amides, aiming to solve the problems of product configuration isomerization, numerous byproducts, and low yield in existing conjugated diene amide synthesis methods. This invention uses (E)-unsaturated aldehydes as raw materials to achieve the conversion of unsaturated aldehydes with double bond configuration retention to conjugated diene carboxylic acid esters. By migrating the double bond of the phosphoryl intermediate, configuration isomerization in traditional methods is avoided, resulting in a single product configuration. The continuous reaction reduces separation losses, and the overall yield is increased by about 20% compared with the prior art. The reaction conditions are mild and suitable for industrial production.

[0006] The purpose of this invention is to provide a method for synthesizing a fully (E)-configured conjugated diene amide, comprising the following steps: At room temperature, using trans-2-octenal of Formula 1 and triethyl phosphoroacetate of Formula 2 as raw materials, a Horner–Wadsworth–Emmons reaction is carried out in tetrahydrofuran solution under the action of sodium hydride to obtain ethyl (2E,4E)-2,4-decadienoate of Formula 3.

[0007] Using ethyl (2E,4E)-2,4-decadienoate of Formula 3 as a raw material, HATU and a base were added, and an amino-ester exchange reaction was carried out at room temperature to obtain the all-(E) configuration conjugated diene amide of Formula 5.

[0008] Alternatively, using ethyl (2E,4E)-2,4-decadienoic acid of Formula 3 as a raw material, water and potassium hydroxide are added, and a hydrolysis reaction is carried out in ethanol solvent at 40°C to obtain (2E,4E)-2,4-decadienoic acid of Formula 4.

[0009] (2E,4E)-2,4-decadienoic acid of formula 4 was dissolved in tetrahydrofuran. Using N,N-dimethylformamide as a catalyst, thionyl chloride and the catalyst were added at -5°C to 5°C to induce an acylation reaction. After filtration, isobutylamine was added to the filtrate, and aminolysis was carried out at room temperature to obtain the fully (E)-configured conjugated diene amide of formula 6. The synthetic route is as follows:

[0010] .

[0011] As a preferred embodiment, 2. The method for synthesizing the all-(E) configuration conjugated diene amide according to claim 1 is characterized in that the molar ratio of trans-2-octenal of Formula 1 to triethyl phosphoroacetate of Formula 2 is 1~1.6:1, and the molar ratio of trans-2-octenal of Formula 1 to sodium hydride is 1:1~1.6.

[0012] In a preferred embodiment, the ratio of trans-2-octenal to water in Formula 1 is 5 mmol: 0.8 mL to 1.2 mL; the molar ratio of trans-2-octenal to potassium hydroxide in Formula 1 is 1: 1.5 to 2.2.

[0013] In a preferred embodiment, the ratio of trans-2-octenal, N,N-dimethylformamide and thionyl chloride in Formula 1 is 1 mol: 1 mL to 1.5 mL: 1 mol.

[0014] In a preferred embodiment, the molar ratio of trans-2-octenal to isobutylamine in Formula 1 is 1:1 to 1.2.

[0015] In a preferred embodiment, the molar ratio of trans-2-octenal of Formula 1 to 1-bis(dimethylamino)methylenebis(dimethylamino)methylene-1H-1,2,3-triazolo-4,5−4,5−bpyridinium-3-hexafluorophosphate oxide (HATU) is 1:1.2~1.5.

[0016] In a preferred embodiment, the molar ratio of trans-2-octenal to the base in Formula 1 is 1:0.1~1.5.

[0017] In a preferred embodiment, the base is triethylamine, N,N-diisopropylethylamine, sodium methoxide, or sodium ethoxide.

[0018] In a preferred embodiment, the alcohol solvent is methanol, ethanol, or isopropanol.

[0019] As a preferred embodiment, after the Horner–Wadsworth–Emmons reaction is completed, the reaction mixture is quenched with a saturated aqueous solution of ammonium chloride, then extracted with ethyl acetate, the organic phases are combined, washed with brine, dried with magnesium sulfate, and concentrated to obtain ethyl (2E,4E)-2,4-decadienoic acid of formula 3.

[0020] As a preferred embodiment, after the hydrolysis reaction is completed, the pH is adjusted to 4, the mixture is extracted with ethyl acetate, the organic phases are combined, washed with brine, dried with magnesium sulfate, and concentrated to obtain (2E,4E)-2,4-decadienoic acid of formula 4.

[0021] In a preferred embodiment, after the amine-ester exchange reaction is completed, brine is added, ethyl acetate is used for extraction, the organic phases are combined, dried over magnesium sulfate and concentrated, and purified by column chromatography to obtain the all-(E) configuration conjugated diene amide of formula 5; after the aminolysis reaction is completed, methanol is used for slurry purification to obtain the all-(E) configuration conjugated diene amide of formula 6.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention provides a method for synthesizing a fully (E)-configured conjugated diene amide, which uses (E)-unsaturated aldehydes as raw materials to achieve the conversion of unsaturated aldehydes with double bond configuration retention to conjugated diene carboxylic acid esters. By migrating the double bond of the phosphoryl intermediate, the method avoids configurational isomerization in traditional methods, resulting in a single product configuration. The continuous reaction reduces separation losses, and the overall yield is increased by about 20% compared with the prior art. The reaction conditions are mild and suitable for industrial production. Attached Figure Description

[0023] Figure 1 The photoluminescence spectrum of ethyl (2E,4E)-2,4-decadienoic acid of formula 3 prepared in Example 1 of this invention is shown.

[0024] Figure 2 The hydrogen spectrum of the fully (E)-configured conjugated diene amide of formula 6 prepared in Example 1 of this invention. Detailed Implementation

[0025] To enable those skilled in the art to better understand and implement the technical solutions of this invention, the invention is further described below with reference to specific embodiments. However, the embodiments are not intended to limit the invention. Unless otherwise specified, the following test methods and detection methods are conventional methods; unless otherwise specified, the reagents and raw materials are commercially available.

[0026] To address existing synthetic methods for conjugated diene amides, a three-step method is disclosed: (E)-oct-2-enal → (E)-oct-2-enoic acid (Jones' reagent oxidation) → (E)-oct-2-enoyl chloride (SOCl2 chlorination) → isobutylamide. In this reaction, the strongly acidic environment during Jones' reagent oxidation induces cis-trans isomerism of the double bond, resulting in a (Z)-configuration proportion of 15%–20% in the product, leading to severe configurational isomerization. Furthermore, the aldehyde group is easily over-oxidized to ketones or carboxylic acid derivatives during the oxidation step, resulting in numerous byproducts. The cumulative product loss during the multi-step separation process in the above reaction results in a low overall yield of only 40%–45%. Based on these technical problems, this invention provides a method for synthesizing fully (E)-configured conjugated diene amides.

[0027] The technical solution of the present invention will be described below.

[0028] This invention provides a method for synthesizing a fully (E)-configured conjugated diene amide, comprising the following steps: At room temperature, using trans-2-octenal of Formula 1 and triethyl phosphoroacetate of Formula 2 as raw materials, a Horner–Wadsworth–Emmons reaction is carried out in tetrahydrofuran solution under the action of sodium hydride to obtain ethyl (2E,4E)-2,4-decadienoate of Formula 3.

[0029] Using ethyl (2E,4E)-2,4-decadienoate of Formula 3 as a starting material, 1-bis(dimethylamino)methylenebis(dimethylamino)methylene-1H-1,2,3-triazolo-4,5−4,5−bpyridinium 3-oxyhexafluorophosphate and a base were added, and an amino-ester exchange reaction was carried out at room temperature to obtain the all-(E) configuration conjugated diene amide of Formula 5.

[0030] Alternatively, using ethyl (2E,4E)-2,4-decadienoic acid of Formula 3 as a raw material, water and potassium hydroxide are added, and a hydrolysis reaction is carried out in ethanol solvent at 40°C to obtain (2E,4E)-2,4-decadienoic acid of Formula 4.

[0031] (2E,4E)-2,4-decadienoic acid of formula 4 was dissolved in tetrahydrofuran. Using N,N-dimethylformamide as a catalyst, thionyl chloride and the catalyst were added at -5°C to 5°C to induce an acylation reaction. After filtration, isobutylamine was added to the filtrate, and aminolysis was carried out at room temperature to obtain the fully (E)-configured conjugated diene amide of formula 6. The synthetic route is as follows:

[0032] .

[0033] In the above-described synthetic method, the conversion of an unsaturated aldehyde with double bond configuration retention to a conjugated diene carboxylic acid ester is achieved using (E)-unsaturated aldehyde as a starting material. The double bond migration of the phosphoryl intermediate avoids the configuration isomerization in traditional methods, resulting in a single product configuration. The continuous reaction reduces separation losses, and the overall yield is about 20% higher than that of the prior art (the yield of the existing synthetic method is 40%~45%, while the yield of this invention is 60%~65%). The reaction conditions are mild and suitable for industrial production.

[0034] The technical effects of the present invention will be described below through the following embodiments.

[0035] Example 1 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (120 mmol) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution of triethyl phosphoroacetate (120 mmol) (25 mL) was added to the above solution, and the mixture was stirred for another 30 min. Then, a tetrahydrofuran solution of trans-2-octenal (100 mmol) (25 mL) was added to carry out the Horner-Wadsworth-Emmons reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain a concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of formula 3.

[0036] S2, the concentrated solution of ethyl (2E,4E)-2,4-decadienoic acid of Formula 3 above was added to ethanol (30 mL), water (20 mL), and potassium hydroxide (200 mmol). The mixture was stirred at 40 °C for 2 hours to carry out hydrolysis reaction to obtain (2E,4E)-2,4-decadienoic acid. The pH was adjusted to 4 with dilute hydrochloric acid to release the obtained (2E,4E)-2,4-decadienoic acid. The mixture was then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain the concentrated solution of the compound of Formula 4.

[0037] S3, the concentrated solution of the compound of Formula 4 above was added to tetrahydrofuran (40 mL), cooled to 0°C in an ice bath, N,N-dimethylformamide (0.1 mL) was added as a catalyst, and thionyl chloride (100 mmol) was added dropwise to induce an acylation reaction. The mixture was stirred at 0±5°C for 1 hour, filtered into a reaction flask, and isobutylamine (100 mmol) was added to continue the aminolysis reaction. The mixture was stirred at room temperature for 2 hours, purified by slurrying with methanol, and a white powder solid was obtained. The HPLC result was >99%, which yielded the all-(E) configuration conjugated diene amide of Formula 6, with a yield of 62%.

[0038] The above synthetic route is shown below: .

[0039] Example 2 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (120 mmol) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution of triethyl phosphoroacetate (120 mmol) (25 mL) was added to the above solution, and the mixture was stirred for another 30 min. Then, a tetrahydrofuran solution of trans-2-octenal (100 mmol) (25 mL) was added to carry out the Horner–Wadsworth–Emmons reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3.

[0040] S2, the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3 above was added to tetrahydrofuran (30 mL), followed by 1-bis(dimethylamino)methylenebis(dimethylamino)methylene-1H-1,2,3-triazolo-4,5−4,5−bpyridinium 3-oxyhexafluorophosphate (HATU) (120 mmol) and sodium methoxide (12 mmol) for amidation reaction. The reaction was carried out at room temperature for 10 h, followed by the addition of brine and extraction with ethyl acetate. The organic phases were combined, dried over magnesium sulfate, concentrated, and purified by column chromatography to obtain a white powder solid with HPLC >99%, which is the all-(E) configuration conjugated diene amide of Formula 5, with a yield of 65%.

[0041] The above synthetic route is shown below: .

[0042] Example 3 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (100 mmol, trans-2-octenal: sodium hydride = 1:1) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution (25 mL) of triethyl phosphoroacetate (100 mmol, trans-2-octenal: triethyl phosphoroacetate = 1:1) was added to the above solution. After stirring for another 30 min, a tetrahydrofuran solution (25 mL) of trans-2-octenal (100 mmol) was added to carry out the Horner-Wadsworth-Emmons reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain a concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3.

[0043] S2, the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3 above was added to ethanol (30 mL), water (16 mL, 5 mmol of trans-2-octenal: 0.8 mL of water) and potassium hydroxide (150 mmol, 1:1.5 of trans-2-octenal: potassium hydroxide) were added and stirred at 40 °C for 2 hours to carry out hydrolysis reaction. The pH was adjusted to 4 with dilute hydrochloric acid to release (2E,4E)-2,4-decadienoic acid. The solution was then extracted with ethyl acetate, the organic phases were combined, washed twice with brine, dried over magnesium sulfate and concentrated to obtain the concentrated solution of the compound of Formula 4.

[0044] S3, the concentrated solution of the above compound 4 was added to tetrahydrofuran (40 mL), cooled to 0 °C in an ice bath, and N,N-dimethylformamide (0.1 mL, trans-2-octenal 1 mol: DMF 1 mL) was added as a catalyst, and thionyl chloride (100 mmol, trans-2-octenal: thionyl chloride = 1:1) was added dropwise to induce an acylation reaction. The mixture was stirred at 0±5 °C for 1 hour, filtered into a reaction flask, and isobutylamine (100 mmol, trans-2-octenal: isobutylamine = 1:1) was added to continue the aminolysis reaction. The mixture was stirred at room temperature for 2 hours, purified by slurrying with methanol, and a white powder solid was obtained. The HPLC result was >99%, which is the all-(E) configuration conjugated diene amide of formula 6, with a yield of 60%.

[0045] The above synthetic route is shown below: .

[0046] Example 4 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (160 mmol, trans-2-octenal: sodium hydride = 1:1.6) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution of triethyl phosphoroacetate (62.5 mmol, trans-2-octenal: triethyl phosphoroacetate = 1.6:1) (25 mL) was added to the above solution. After stirring for another 30 min, a tetrahydrofuran solution of trans-2-octenal (100 mmol) (25 mL) was added to carry out the Horner-Wadsworth-Emmons reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain a concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3.

[0047] S2, the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3 above was added to ethanol (30 mL), water (24 mL, 5 mmol of trans-2-octenal: 1.2 mL of water) and potassium hydroxide (220 mmol, 1:2.2 of trans-2-octenal: potassium hydroxide = 1:2.2) and stirred at 40 °C for 2 hours to carry out hydrolysis reaction. The pH was adjusted to 4 with dilute hydrochloric acid to release (2E,4E)-2,4-decadienoic acid. The solution was then extracted with ethyl acetate, the organic phases were combined, washed twice with brine, dried over magnesium sulfate and concentrated to obtain the concentrated solution of the compound of Formula 4.

[0048] S3, the concentrated solution of Formula 4 above was added to tetrahydrofuran (40 mL), cooled to 0 °C in an ice bath, and N,N-dimethylformamide (0.15 mL, trans-2-octenal 1 mol: DMF 1.5 mL) was added as a catalyst, and thionyl chloride (100 mmol, trans-2-octenal: thionyl chloride = 1:1) was added dropwise to induce an acylation reaction. The mixture was stirred at 0±5 °C for 1 hour, filtered into a reaction flask, and isobutylamine (120 mmol, trans-2-octenal: isobutylamine = 1:1.2) was added to continue the aminolysis reaction. The mixture was stirred at room temperature for 2 hours, purified by slurrying with methanol, and a white powder solid was obtained. The HPLC result was >99%, which is the all-(E) configuration conjugated diene amide of Formula 6, with a yield of 63%.

[0049] The above synthetic route is shown below: Example 5 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (140 mmol, trans-2-octenal: sodium hydride = 1:1.4) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution of triethyl phosphoroacetate (83.3 mmol, trans-2-octenal: triethyl phosphoroacetate = 1.2:1) (25 mL) was added to the above solution. After stirring for another 30 min, a tetrahydrofuran solution of trans-2-octenal (100 mmol) (25 mL) was added to carry out the Horner-Wadsworth-Emmons reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain a concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of formula 3.

[0050] S2, the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3 above was added to tetrahydrofuran (30 mL), and HATU (135 mmol, trans-2-octenal:HATU=1:1.35) and triethylamine (10 mmol, trans-2-octenal:triethylamine=1:0.1) were added to carry out the amidation reaction. The reaction was carried out at room temperature for 10 h, brine was added, and the mixture was extracted with ethyl acetate. The organic phases were combined, dried over magnesium sulfate, concentrated, and purified by column chromatography to obtain a white powder solid with HPLC >99%, which is the all-(E) configuration conjugated diene amide of Formula 5, with a yield of 61%.

[0051] The above synthetic route is shown below: .

[0052] Example 6 A method for synthesizing a fully (E)-configured conjugated diene amide includes the following steps: S1, at room temperature, sodium hydride (130 mmol, trans-2-octenal: sodium hydride = 1:1.3) was added to tetrahydrofuran (100 mL), and the mixture was stirred for 30 min. Then, a tetrahydrofuran solution of triethyl phosphoroacetate (83.3 mmol, trans-2-octenal: triethyl phosphoroacetate = 1.2:1) (25 mL) was added to the above solution. After stirring for another 30 min, a tetrahydrofuran solution of trans-2-octenal (100 mmol) (25 mL) was added to carry out the Horner-Wadsworth-Emmons-reaction. The mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride and then extracted with ethyl acetate. The organic phases were combined, washed twice with brine, dried over magnesium sulfate, and concentrated to obtain a concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3.

[0053] S2, the concentrated solution of (2E,4E)-2,4-decadienoic acid ethyl ester of Formula 3 above was added to tetrahydrofuran (30 mL), and HATU (150 mmol, trans-2-octenal:HATU=1:1.5) and N,N-diisopropylethylamine (150 mmol, trans-2-octenal:N,N-diisopropylethylamine=1:1.5) were added to carry out the amidation reaction. The reaction was carried out at room temperature for 10 h, brine was added, and the mixture was extracted with ethyl acetate. The organic phases were combined, dried over magnesium sulfate, concentrated, and purified by column chromatography to obtain a white powder solid with HPLC >99%, which is the all-(E) configuration conjugated diene amide of Formula 5, with a yield of 62%.

[0054] The above synthetic route is shown below: .

[0055] The characterization spectral data of the all-(E) configuration conjugated diene amides prepared in Examples 1 to 6 above are as follows.

[0056] NMR data for ethyl (2E,4E)-2,4-decadienoate of Formula 3: 1 H NMR (400 MHz, CDCl3) δ 7.23– 7.15 (m, 1H), 6.16 – 5.97 (m, 2H), 5.71 (d, J =15.4 Hz, 1H), 4.08 – 3.99 (m,2H), 2.16 – 2.03 (m, 4H), 1.36 (p, J =7.2 Hz, 4H), 0.86 – 0.76 (m, 6H). NMR data for the all-(E) configuration conjugated dienoic acid of Formula 6: 1 H NMR (400 MHz, CDCl3) δ 7.12 (dd, J =15.0, 9.9 Hz, 1H), 6.12 – 5.93 (m, 2H), 5.68 (d, J =15.0 Hz, 1H), 5.40 (s,1H), 3.10 (t, J = 6.5 Hz, 2H), 2.07 (q, J = 6.9 Hz, 2H), 1.73 (dt, J =13.5, 6.7 Hz, 1H), 1.35 (p, J =7.2 Hz, 2H), 1.22 (dtd, J=12.8, 6.8, 4.0Hz, 4H), 0.83 (dd, J =18.9, 6.9 Hz, 10H). Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for synthesizing a fully (E)-configured conjugated diene amide, characterized in that, Includes the following steps: At room temperature, using trans-2-octenal of Formula 1 and triethyl phosphoroacetate of Formula 2 as raw materials, Horner–Wadsworth–Emmons reaction is carried out in tetrahydrofuran solution under the action of sodium hydride to obtain ethyl (2E,4E)-2,4-decadienoate of Formula 3. Using ethyl (2E,4E)-2,4-decadienoate of Formula 3 as a starting material, 1-bis(dimethylamino)methylenebis(dimethylamino)methylene-1H-1,2,3-triazolo-4,5−4,5−bpyridinium 3-oxyhexafluorophosphate and a base were added, and an amino-ester exchange reaction was carried out at room temperature to obtain the all-(E) configuration conjugated diene amide of Formula 5; Alternatively, using ethyl (2E,4E)-2,4-decadienoic acid of formula 3 as a raw material, water and potassium hydroxide are added, and a hydrolysis reaction is carried out in an alcohol solvent at 40°C to obtain (2E,4E)-2,4-decadienoic acid of formula 4. The (2E,4E)-2,4-decadienoic acid of formula 4 was dissolved in tetrahydrofuran. Using N,N-dimethylformamide as a catalyst, thionyl chloride and the catalyst were added at -5℃ to 5℃ to induce an acylation reaction. After filtration, isobutylamine was added to the filtrate, and an aminolysis reaction was carried out at room temperature to obtain the all-(E) configuration conjugated diene amide of formula 6. The synthetic route is as follows: 。 2. The method for synthesizing the fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The molar ratio of trans-2-octenal of Formula 1 to triethyl phosphoroacetate of Formula 2 is 1 to 1.6:1, and the molar ratio of trans-2-octenal of Formula 1 to sodium hydride is 1:1 to 1.

6.

3. The method for synthesizing the fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The ratio of trans-2-octenal to water in Formula 1 is 5 mmol: 0.8 mL to 1.2 mL; the molar ratio of trans-2-octenal to potassium hydroxide in Formula 1 is 1: 1.5 to 2.

2.

4. The method for synthesizing the fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The ratio of trans-2-octenal, N,N-dimethylformamide to thionyl chloride in Formula 1 is 1 mol: 1 mL to 1.5 mL: 1 mol.

5. The method for synthesizing a fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The molar ratio of trans-2-octenal to isobutylamine in Formula 1 is 1:1 to 1.

2.

6. The method for synthesizing a fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The molar ratio of trans-2-octenal of Formula 1 to 1-bis(dimethylamino)methylenebis(dimethylamino)methylene-1H-1,2,3-triazolo-4,5−4,5−bpyridinium 3-hexafluorophosphate is 1:1.2~1.

5.

7. The method for synthesizing a fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The molar ratio of trans-2-octenal to the base in Formula 1 is 1:0.1~1.

5.

8. The method for synthesizing the fully (E)-configured conjugated diene amide according to claim 7, characterized in that, The base is triethylamine, N,N-diisopropylethylamine, sodium methoxide, or sodium ethoxide.

9. The method for synthesizing a fully (E)-configured conjugated diene amide according to claim 1, characterized in that, The alcohol solvent is methanol, ethanol, or isopropanol.

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