CN101973903A - Method for synthesizing capsaicin homolog - Google Patents

Abstract

式(1)The present invention relates to the chemical synthesis method of capsaicin homologue, the structure of capsaicin homologue is as shown in formula (1), wherein, R ₁ is an alkyl, cycloalkyl or aryl group between 2-20 carbon atoms ; R ₂ is -H or -OCH ₃ ; R ₃ is -H, -OCH ₃ or -OH, the synthesis method steps include: in the presence of ammonium acetate catalyst, vanillin, 4-hydroxybenzaldehyde, 3-methoxy Base benzaldehyde or 3,4-dimethoxybenzaldehyde and excess nitromethane react under reflux in glacial acetic acid; -Hydroxy-β-nitrostyrene, 3-methoxy-β-nitrostyrene or 3,4-dimethoxy-β-nitrostyrene is reduced with a reducing agent and then acidified; acidified to obtain The reaction of phenethylamine salt with alkyl acid chloride can be done. The preparation process of the invention is simple, the raw materials are easy to obtain, and the reaction conditions are mild, which provides a new development space for the research of capsaicin substances.

Formula 1)

Description

The synthetic method of capsaicin homologue

technical field

The present invention relates to the chemical synthesis method of capsaicin homologue.

Background technique

The fruit of the capsicum plant (capsicum genus) is one of the most consumed condiments worldwide. These pepper fruits contain at least 15 kinds of capsaicinoids that can produce a spicy taste, namely capsaicin (N-(4-hydroxy-3-methoxybenzyl)-8-methyl-6-nonenamide) , Dihydrocapsaicin (N-(4-hydroxy-3-methoxybenzyl)-8-methylnonanamide), norcapsaicin (N-(4-hydroxy-3-methoxybenzyl)- 7-methyl-5-octenamide), nordihydrocapsaicin I (N-(4-hydroxy-3-methoxybenzyl)-7-methyloctylamide), nordihydrocapsaicin II ( N-(4-hydroxy-3-methoxybenzyl)-6-methyloctylamide), norcapsaicin (N-(4-hydroxy-3-methoxybenzyl)-6-methyl- 4-heptenamide), homocapsaicin I (N-(4-hydroxy-3-methoxybenzyl)-9-methyl-7-decenamide), homodihydrocapsaicin I (N-(4 -Hydroxy-3-methoxybenzyl)-9-methyldecylamide), homocapsaicin II (N-(4-hydroxy-3-methoxybenzyl)-8-methyl-6-decene amide), homodihydrocapsaicin II (N-(4-hydroxy-3-methoxybenzyl)-8-methyldecylamide), homocapsaicin III (N-(4-hydroxy-3-methoxy Benzyl)-9-methyl-6-decenylamide), homocapsaicin (N-(4-hydroxy-3-methoxybenzyl)-10-methyl-8-undecenamide), Homocapsaicin (N-(4-hydroxy-3-methoxybenzyl)-11-methyl-9-dodecenamide), octanoyl vitanolamine (N-(4-hydroxy-3- Methoxybenzyl)-octylamide), nonanoyl vitanamide (N-(4-hydroxy-3-methoxybenzyl)-nonanamide), decanoyl vitanamide (N-(4-hydroxy- 3-methoxybenzyl)-decylamide).

Among the natural capsaicin substances, capsaicin (46%～69%), dihydrocapsaicin (21%～40%), nordihydrocapsaicin (～7%), homodihydrocapsaicin (I) (～1 %), homocapsaicin (I) (～1%), and all the other capsaicinoid substances are trace amounts. Among them, capsaicin has the highest spiciness, as high as 16,000,000 Scoville Heat Unit (SHU); followed by dihydrocapsaicin, which is 15,000,000 SHU; 9,100,000 SHU, 8,600,000 SHU, 8,6000,000 SHU.

In addition to natural capsaicin-like substances, there are many capsaicin homologues that also have spiciness. The structural formula of capsaicin homologue is such as formula (1)

式(1)

Formula 1)

Wherein, R ₁ is an alkyl, cycloalkyl or aryl group with carbon atoms between 2-20; R ₂ is -H or -OCH ₃ ; R ₃ is -H, -OCH ₃ or -OH.

The sensory analysis results of capsaicinoids and capsaicin homologues show that the spiciness is largely dependent on their molecular structural features:

(1) The para-hydroxyl of the benzene ring plays a very important role in the hotness of capsaicinoids. When it is closed or replaced by other atoms or functional groups, the hotness of capsaicinoids is greatly reduced, even disappear.

(II) When the benzene ring has an ortho hydroxyl group, the capsaicinoid substance also has a certain degree of spicyness, but its spicy degree is far less than that of the capsaicinoid substance with a hydroxyl group at the para-position of the benzene ring.

(III) The exchange of -NH- and -CO- positions in the amide group has no obvious negative impact on the pungency of capsaicinoids, but slightly increases the pungency.

(IV) The amide group, or even the N atom therein, is not an indispensable factor for capsaicinoids to produce a spicy taste, but they just play a role in enhancing the spicy taste.

(V) Only aliphatic side chains can produce hotness, straight chain or cyclic fatty side chains can be used.

(VI) C ₉ -C ₁₁ straight-chain amide compounds have the highest spiciness, and when the aliphatic side chain is too long or too short, the pungency will decrease obviously. For example, when the alkyl side chain is longer than 12 carbon atoms or shorter than 6 carbon atoms, there will be no obvious spiciness.

Capsaicin has various pharmacological effects due to its pungent taste, such as analgesia, anti-inflammation, treatment of frostbite, antipruritic, sterilization, rheumatism, etc.; it is mainly used clinically to treat refractory diabetic neuralgia and severe psoriasis It is used as an environment-friendly green bio-pesticide in agricultural production; it is used as a repellant in ship antifouling coatings to prevent marine organisms from adhering; it can be added to the sheath of wires, cables, and optical cables to prevent food from mice and termites. It can also be used to make tear gas bombs and police defense weapons.

At present, there are relatively few studies on the preparation of capsaicin and its derivatives by chemical synthesis. Harumi Kaga etc. reported the synthetic method of capsaicin [Harumi Kaga, Masakatsu Miura, Kazuhiko Orito.AFacile Procedure for Synthesis of Capsaicin.J.Org.Chem.1989,54,3477-3478]; Peter M.Gannett etc. reported Synthesis of capsaicinoids [Peter M.Gannett, Donald L.Nagel, Pam J.Reilly, Terence Lawson, Jody Sharpe, Bela Toth.The Capsaicinoids: Their Separation, Synthesis and Mutagenicity.J.Org.Chem.1988, 53 : 1064-1071]; Yang Yan etc. reported the synthesis method of capsaicin and capsaicin [Yang Yan, Jin Yongsheng, Dong Zhenxiu etc. Synthesis of capsaicin and capsaicin. Chemical Journal of Chinese Universities. 2007, 28 (7): 1310-1312]. Zhou Shengze and others reported the artificial synthesis method of capsaicin homologue (Zhou Shengze, Zhou Xiangfeng, Peng Bixian. Artificial synthesis method of capsaicin homologue. Patent No.: 200910087705.0.). But about the capsaicin homologue as shown in general formula (1) (wherein, R ₁ is an alkyl, cycloalkyl or aryl group between 2-20 carbon atoms; R ₂ is -H or -OCH ₃ ; R ₃ is-H,-OCH ₃ or-OH.) The chemical synthesis of seldom reported.

Contents of the invention

The purpose of the present invention is to provide a kind of chemical synthesis method of capsaicin homologue with simple and convenient preparation technology.

The chemical synthesis method of capsaicin homologue of the present invention, the structural formula of said capsaicin homologue is as formula (1)

Formula 1)

Wherein, R ₁ is an alkyl, cycloalkyl or aryl group with carbon atoms between 2-20; R ₂ is -H or -OCH ₃ ; R ₃ is -H, -OCH ₃ or -OH,

Its chemical synthesis method comprises the following steps:

1) In the presence of an ammonium acetate catalyst, vanillin, 4-hydroxybenzaldehyde, 3-methoxybenzaldehyde or 3,4-dimethoxybenzaldehyde and excess nitromethane are refluxed in glacial acetic acid reaction to give the corresponding 4-hydroxy-3-methoxy-β-nitrostyrene, 4-hydroxy-β-nitrostyrene, 3-methoxy-β-nitrostyrene or 3,4- Dimethoxy-β-nitrostyrene.

2) 4-hydroxyl-3-methoxy-β-nitrostyrene, 4-hydroxyl-β-nitrostyrene, 3-methoxyl-β-nitrostyrene or 3-nitrostyrene obtained in step 1) , 4-dimethoxy-β-nitrostyrene is reduced with a reducing agent, and then acidified with an acid solution to obtain the corresponding 4-hydroxyl-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt.

3) 4-hydroxy-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt and alkyl Acid chloride reaction, 4-hydroxy-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt with alkyl The mol ratio of acid chloride is 1:1-1:1.2, obtains the crude product of capsaicin homologue as shown in structural formula (1).

A further feature of the present invention is that the crude product of capsaicin homologue is dissolved in ether, then petroleum ether is added for recrystallization and purification, and the volume ratio of ether and petroleum ether is 1:1 to 1:10.

In the present invention, the reducing agent is LiAlH ₄ or reduction with H ₂ in the presence of Pd/C. Said acid solution is an aqueous solution of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid or nitric acid.

The alkyl acid chloride is acetyl chloride, propionyl chloride, butyryl chloride, valeryl chloride, hexanoyl chloride, heptanoyl chloride, octanoyl chloride, nonanoyl chloride, benzoyl chloride or cyclohexaneyl chloride.

The method for synthesizing capsaicin homologues disclosed by the invention has the advantages of simple and convenient preparation process, easy-to-obtain raw materials and mild reaction conditions, which provides a new development space for the research of capsaicin-like substances.

Detailed ways

Below in conjunction with embodiment further illustrate the present invention.

Example 1

(1) Synthesis of 4-hydroxy-β-nitrostyrene

Add 6.1g of 4-hydroxybenzaldehyde, 3.2g of ammonium acetate, 10mL of nitromethane and 25mL of glacial acetic acid into a 250mL single-necked flask, start the electromagnetic stirrer and heat it, and make it reflux in an oil bath at 120-130°C for 3h . Heating was stopped, cooled to room temperature, the reaction solution was poured into ice water, a red-yellow precipitate was precipitated, filtered, and the filter cake was recrystallized three times with a solution of ethanol/water (the volume ratio of ethanol/water was 2/5) to obtain yellow The powder 5.2g, yield 63%.

(2) Synthesis of 4-hydroxyphenethylamine hydrochloride

Add 4.8g of lithium aluminum hydride and 300mL of anhydrous ether into a 500mL single-necked flask, add 4.9g of 4-hydroxy-β-nitrostyrene into a Soxhlet drawer, and carry out the extraction and reduction reaction for 52 hours until the extract is It is colorless. Cool to room temperature, add about 80ml of deionized water dropwise, and then adjust the pH value of the solution to between 5 and 6 with 1mol/L hydrochloric acid. There is a large amount of precipitation in the solution, so filter it. Weigh 7.5 g of picric acid and dissolve with as little hot ethanol as possible. The above filtrate was heated to near boiling, then a hot ethanol solution of picric acid was added, and the reaction was stirred at 90°C for 1 hour. After standing overnight at room temperature, crystals precipitated and were filtered. Dissolve the crystal in 150ml of boiling water, add 40ml of concentrated hydrochloric acid, reflux for 0.5h, cool down, a solid precipitates, filter, and the filtrate is washed with nitrobenzene and ether in turn. The filtrate was distilled off under reduced pressure to obtain 3.6 g of crude product of 4-hydroxyphenethylamine hydrochloride with a yield of 70%. The crude product was recrystallized from methanol-ethyl acetate to obtain 3.1 g of pure product.

(3) Synthesis of N-[2-(4-hydroxyphenyl) ethyl] benzamide

Weigh 1.8g of benzoic acid and 10mL of thionyl chloride into a 150ml three-neck flask, heat and stir under the protection of nitrogen, and react under reflux for 1h. Lower the temperature to about 50°C, and distill off excess thionyl chloride under reduced pressure. After cooling down to room temperature, 25ml of anhydrous diethyl ether was added.

Add 2.5g of 4-hydroxyphenethylamine hydrochloride to 2.4g of saturated sodium bicarbonate solution, and stir at room temperature until the hydrochloride is evenly dispersed in the solution. Add benzoyl chloride ethyl ether solution slowly, react for 1h, then add 50ml of anhydrous ether, continue to react for 0.5h. Let stand in a separatory funnel, separate the water layer, and wash the ether layer with 1 mol/L hydrochloric acid and saturated sodium bicarbonate solution successively, and then dry it with anhydrous sodium sulfate. Filtrate, and distill off the diethyl ether under reduced pressure to obtain 2.4 g of crude product with a yield of 69%. The crude product was dissolved in diethyl ether, and then petroleum ether was added for recrystallization and purification. The volume ratio of diethyl ether and petroleum ether was 1:1. That is, pure capsaicin homologue N-[2-(4-hydroxyphenyl)ethyl]benzamide.

Example 2

(1) Synthesis of 3,4-dimethoxy-β-nitrostyrene

Add 16.6g of 3,4-dimethoxybenzaldehyde, 10.0g of ammonium acetate, 20mL of nitromethane and 60mL of glacial acetic acid into a 250mL single-necked flask. The reaction was refluxed in the bath for 2h. Heating was stopped, cooled to room temperature, the reaction solution was poured into ice water, precipitated, filtered, and the filter cake was recrystallized three times with a solution of ethanol/water (the volume ratio of ethanol/water was 3/5) to obtain 11.3 g of solid powder , yield 54%.

(2) 3, the synthesis of 4-dimethoxyphenethylamine hydrochloride

In a 250mL three-necked reaction flask, add 8.3g of 3,4-dimethoxy-β-nitrostyrene, 150mL of absolute ethanol, 10mL of concentrated hydrochloric acid, and 5.0g of 10% palladium carbon in sequence. , Hydrogenation reaction at room temperature and pressure for 4h. The catalyst was filtered off, and the solvent was distilled off from the filtrate under reduced pressure to obtain an off-white solid, 9.9 g, with a yield of 91%. The crude product was recrystallized from methanol-ethyl acetate to obtain 7.2 g of pure product.

(3) Synthesis of N-[2-(3,4-dimethoxyphenyl)ethyl]cyclohexaneamide

Weigh 1.4g of cyclohexanecarboxylic acid and 10mLg of thionyl chloride into a 150ml three-neck flask, heat and stir under nitrogen protection, and reflux for 1h. Lower the temperature to about 50°C, and distill off excess thionyl chloride under reduced pressure. After cooling down to room temperature, 10ml of anhydrous diethyl ether was added.

Add 2.2 g of 3,4-dimethoxyphenethylamine hydrochloride to 1.8 g of saturated sodium bicarbonate solution, and stir at room temperature until the hydrochloride is evenly dispersed in the solution. Slowly add cyclohexane acyl chloride ethyl ether solution, react for 0.5h, then add 30ml of anhydrous ether, continue to react for 0.5h. Let stand in a separatory funnel, separate the water layer, and wash the ether layer with 1 mol/L hydrochloric acid and saturated sodium bicarbonate solution successively, and then dry it with anhydrous sodium sulfate. Filter and distill off ether under reduced pressure to obtain 1.7 g of crude product, yield: 59%. The crude product was dissolved in diethyl ether, and then petroleum ether was added for recrystallization and purification. The volume ratio of diethyl ether and petroleum ether was 1:5. 1.1 g of pure capsaicin homologue N-[2-(3,4-dimethoxyphenyl)ethyl]cyclohexaneamide was obtained.

Example 3

(1) Synthesis of 4-hydroxy-3-methoxy-β-nitrostyrene

Add 18.6g of vanillin, 9.0g of ammonium acetate, 19.5mL of nitromethane and 53mL of glacial acetic acid into a 250mL single-necked flask, turn on the electromagnetic stirrer and heat, and make it reflux in an oil bath at 120-130°C for 2h. Stop heating, cool to room temperature, pour the reaction solution into ice water, a red-yellow precipitate is precipitated, filter, and the filter cake is recrystallized three times with a solution of ethanol/water (the volume ratio of ethanol/water is 3/2) to obtain yellow The powder 11.1g, yield 46%.

(2) Synthesis of 4-hydroxyl-3-methoxyphenethylamine hydrochloride

Add 2.4g of lithium aluminum hydride and about 200mL of anhydrous ether into a 250mL single-necked flask, add 2.5g of 4-hydroxy-3-methoxy-β-nitrostyrene into a Soxhlet drawer, and perform 60 extraction reactions Hour. Cool to room temperature, slowly add about 40ml of deionized water, then adjust the pH value of the solution to 5-6 with 1mol/L hydrochloric acid, a large amount of precipitates precipitate in the solution, heat to boil, filter while hot to remove the precipitates. Weigh 3.2g of picric acid, dissolve it in as little hot ethanol as possible, add it to the above hot filtrate, and stir for 1 hour to react. After standing overnight at room temperature, yellow crystals precipitated and were filtered. Dissolve the yellow crystals in 90ml of boiling water, add 18.2ml of concentrated hydrochloric acid, a large amount of solid precipitates during cooling, filter, and wash the filtrate with nitrobenzene and ether in turn. Water was distilled off from the filtrate under reduced pressure to obtain a crude product of 4-hydroxy-3-methoxy-phenethylamine hydrochloride. The crude product was recrystallized from methanol-ethyl acetate to obtain 0.9 g of the final product with a yield of 38%.

(3) Synthesis of N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]nonanamide

Weigh 0.9g nonanoic acid and 2.3g thionyl chloride into a 150ml three-neck flask, heat and stir under nitrogen protection, and react under reflux for 1h. Lower the temperature to about 50°C, and distill off excess thionyl chloride under reduced pressure. After cooling down to room temperature, 25ml of anhydrous diethyl ether was added.

Add 1.0 g of 4-hydroxy-3-methoxyphenethylamine hydrochloride to 1.6 g of saturated sodium bicarbonate solution, and stir at room temperature until the hydrochloride is evenly dispersed in the solution. Add nonanoyl chloride ethyl ether solution slowly, react for 0.5h, then add 30ml of anhydrous ether, continue to react for 0.5h. Let stand in a separatory funnel, separate the water layer, and wash the ether layer with 1 mol/L hydrochloric acid and saturated sodium bicarbonate solution successively, and then dry it with anhydrous sodium sulfate. Filter and distill off ether under reduced pressure to obtain 1.1 g of crude product, yield: 73%. . The crude product was dissolved in diethyl ether, and then petroleum ether was added for recrystallization and purification. The volume ratio of diethyl ether and petroleum ether was 1:10. The pure capsaicin homologue N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]nonanamide was obtained.

Example 4

(1) Synthesis of 3-methoxy-β-nitrostyrene

Add 6.8g of 3-methoxybenzaldehyde, 5.2g of ammonium acetate, 15mL of nitromethane and 25mL of glacial acetic acid into a 250mL single-necked flask, start the electromagnetic stirrer and heat it to reflux in an oil bath at 120-130°C Reaction 2h. Heating was stopped, cooled to room temperature, the reaction solution was poured into ice water, a large amount of precipitate was separated out, filtered, and the filter cake was recrystallized three times with a solution of ethanol/water (the volume ratio of ethanol/water was 3/7) to obtain solid powder 4.4 g, yield 49%.

(2) Synthesis of 3-methoxyphenethylamine hydrochloride

In a 250mL three-necked reaction flask, add 3.6g of 3-methoxy-β-nitrostyrene, 50mL of absolute ethanol, 5mL of concentrated hydrochloric acid, and 1.2g of 10% palladium carbon in sequence. Pressure hydrogenation reaction 6h. The catalyst was filtered off, and the solvent was distilled off from the filtrate under reduced pressure to obtain an off-white solid, 3.3 g, with a yield of 89%. The crude product was recrystallized from methanol-ethyl acetate to obtain 2.7 g of pure product.

(3) Synthesis of N-[2-(3-methoxyphenyl)ethyl]acetamide

Weigh 0.7g of acetic acid and 8mL of thionyl chloride into a 150ml three-necked flask, heat and stir under nitrogen protection, and reflux for 1h. Lower the temperature to about 50°C, and distill off excess thionyl chloride under reduced pressure. After cooling down to room temperature, 10ml of anhydrous diethyl ether was added.

Add 1.9 g of 3-methoxyphenethylamine hydrochloride to 1.7 g of saturated sodium bicarbonate solution, and stir at room temperature until the hydrochloride is evenly dispersed in the solution. Add acetyl chloride ethyl ether solution slowly, react for 0.5h, then add 30ml of anhydrous ether, continue to react for 0.5h. Let stand in a separatory funnel, separate the water layer, and wash the ether layer with 1 mol/L hydrochloric acid and saturated sodium bicarbonate solution successively, and then dry it with anhydrous sodium sulfate. Filter and distill off ether under reduced pressure to obtain 1.2 g of crude product, yield: 65%. . The crude product was dissolved in diethyl ether, and then petroleum ether was added for recrystallization and purification. The volume ratio of diethyl ether and petroleum ether was 1:8. The pure capsaicin congener N-[2-(3-methoxyphenyl)ethyl]acetamide was obtained.

The above specific embodiments are used to explain the present invention, rather than to limit the present invention. Within the spirit of the present invention and the protection scope of the claims, any modification and change made to the present invention will fall into the protection scope of the present invention. For example, in the above examples, the alkyl acid chlorides used are acetyl chloride, nonanoyl chloride, cyclohexanoyl chloride, benzoyl chloride, wherein propionyl chloride, butyryl chloride, pentanoyl chloride, hexanoyl chloride, heptanoyl chloride, octanoyl chloride in the alkyl chain The number of C atoms is between acetyl chloride and nonanoyl chloride, obviously also suitable for the present invention.

Claims (5)

1. the chemical synthesis method of capsaicin homologue, the structural formula of said capsaicin homologue is as formula (1)

Formula 1) Wherein, R ₁ is an alkyl, cycloalkyl or aryl group with carbon atoms between 2-20; R ₂ is -H or -OCH ₃ ; R ₃ is -H, -OCH ₃ or -OH, Its chemical synthesis method comprises the following steps: 1) In the presence of an ammonium acetate catalyst, vanillin, 4-hydroxybenzaldehyde, 3-methoxybenzaldehyde or 3,4-dimethoxybenzaldehyde and excess nitromethane are refluxed in glacial acetic acid reaction to give the corresponding 4-hydroxy-3-methoxy-β-nitrostyrene, 4-hydroxy-β-nitrostyrene, 3-methoxy-β-nitrostyrene or 3,4- Dimethoxy-β-nitrostyrene. 2) 4-hydroxyl-3-methoxy-β-nitrostyrene, 4-hydroxyl-β-nitrostyrene, 3-methoxyl-β-nitrostyrene or 3-nitrostyrene obtained in step 1) , 4-dimethoxy-β-nitrostyrene is reduced with a reducing agent, and then acidified with an acid solution to obtain the corresponding 4-hydroxyl-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt. 3) 4-hydroxy-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt and alkyl Acid chloride reaction, 4-hydroxy-3-methoxyphenethylamine salt, 4-hydroxyphenethylamine salt, 3-methoxyphenethylamine salt or 3,4-dimethoxyphenethylamine salt with alkyl The mol ratio of acid chloride is 1:1-1:1.2, obtains the crude product of capsaicin homologue as shown in structural formula (1). 2. the chemical synthesis method of capsaicin homologue according to claim 1 is characterized in that the thick product of capsaicin homologue is dissolved with ether, then adds sherwood oil, carries out recrystallization purification, and the volume ratio of ether and sherwood oil is 1:1～1:10. 3. the chemical synthesis method of capsaicin homologue according to claim 1 is characterized in that described reducing agent is LiAlH ₄ or in the presence of Pd/C with H ₂ reduction. 4. the chemical synthesis method of capsaicin homologue according to claim 1 is characterized in that said acid solution is the aqueous solution of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid or nitric acid. 5. the chemical synthesis method of capsaicin homologue according to claim 1 is characterized in that described alkyl acid chloride is acetyl chloride, propionyl chloride, butyryl chloride, pentanoyl chloride, hexanoyl chloride, heptanoyl chloride, octanoyl chloride, nonyl chloride acyl chloride, benzoyl chloride or cyclohexane acyl chloride.