CN111187161B - Preparation method of dihydrocapsaicin and dihydrocapsaicin ester - Google Patents
Preparation method of dihydrocapsaicin and dihydrocapsaicin ester Download PDFInfo
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- CN111187161B CN111187161B CN202010066991.9A CN202010066991A CN111187161B CN 111187161 B CN111187161 B CN 111187161B CN 202010066991 A CN202010066991 A CN 202010066991A CN 111187161 B CN111187161 B CN 111187161B
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
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- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
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Abstract
The invention relates to a preparation method of dihydrocapsaicin and dihydrocapsaicin ester, which specifically comprises the following steps: (1) condensing furfural and methyl isopropyl ketone under an alkaline condition to obtain a condensation product A; (2) the condensation product A is subjected to ring opening in water or alcohol under acidic conditions to obtain 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate; (3) hydrogenating and deoxidizing 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate, hydrogen, trifluoromethanesulfonate and a hydrogenation catalyst to obtain 8-methyl nonanoic acid; (4) 8-methyl nonanoic acid reacts with vanillylamine or vanillyl alcohol under the action of a catalyst to generate dihydrocapsaicin or dihydrocapsaicin ester. The invention has the advantages of good atomic economy, high product yield, high product purity, small environmental pollution, simple process route, convenient operation, suitability for industrial large-scale production, wide application field of the dihydrocapsaicin and the dihydrocapsaicin ester, and good market prospect. The method has the advantages of wide raw material source, low price, easy obtainment, simple operation, cost reduction and suitability for industrial production.
Description
Technical Field
The invention relates to a preparation method of dihydrocapsaicin or dihydrocapsaicin ester, belonging to the field of medicines and food additives.
Background
Capsaicin in pepper fruits is widely applied to a plurality of fields such as agriculture, processing industry, food and restaurant industry, medical industry, feed industry, military and the like. Capsaicin of capsicum fruits is used as a pollution-free spicy antifouling paint additive in the production of marine coatings; the compound is used as an environment-friendly green biopesticide in agricultural production; the termite-proof coating is added into the sheaths of electric wires, cables and optical cables to prevent mice and termites from eating and damaging; it can also be used for manufacturing tear shells, police defense weapons and the like, and has economic value far higher than the edible value. The research on capsaicin compounds in China still belongs to the initial stage, and the current research is more intensive and belongs to the field of medicines. The research on the aspects of analgesia, anti-tumor, anti-inflammatory and the like of capsaicin has been advanced to a certain extent, however, the research pepper compound in the field has to depend on foreign import, so that the research process and the clinical application are limited to different degrees.
Wherein the dihydrocapsaicin and dihydrocapsaicin ester have antibacterial and disinfectant effects, and can be used as food antiseptic; has strong and durable anti-inflammatory analgesic effect and antibacterial and anti-tumor effects; has effects in promoting gastrointestinal motility and gastric secretion, and promoting digestion; has effects in dilating capillary, improving local blood circulation, and promoting metabolism of analgesic substances.
At present, the high-purity natural capsaicin is expensive, so that the application of the high-purity natural capsaicin in low-end markets such as biological pesticides, chemical coatings and the like is limited, and the high-purity natural capsaicin can only be used in high-end markets such as food health care, pharmaceutical industry and the like.
Dihydrocapsaicin is usually prepared by extraction from natural capsicum. Early methods consisted of pulverizing fresh red dried peppers, extracting with organic solvents such as ether or ethanol, concentrating to obtain a dark red to orange red oily liquid, which is commonly called as pepper oleoresin internationally, and the yield of this step was generally about 1% of the weight of the dried fruit. The capsicum oleoresin is further extracted and concentrated by ethyl ether, diluted ethanol and alkaline aqueous solution or solvents such as petroleum ether, dichloroethane and the like, and then crystallized by petroleum ether or n-hexane to obtain crude capsaicin crystals. The extraction of capsaicin with chemical reagent has the advantages of great leaching capacity, easy industrial production, etc. but the obtained capsaicin product has low purity and great production consumption, belongs to mixed product and is difficult to raise product efficiency.
With the continuous development of biological and chemical technologies, the preparation of capsaicin by using a biological synthesis method and a chemical synthesis method has a good prospect, but the two methods still have some problems which are difficult to solve at present, such as high raw material cost and difficulty in realizing industrialization.
Among them, the selective hydrodeoxygenation preparation of 8-methylnonanoic acid from 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate is a key step of the overall reaction. The conventional methods for converting the ketocarbonyl group into the methylene group mainly include Wolff-Kishner reaction and Clemenson reaction. However, hydrazine hydrate in the Wolff-Kishner reaction has the disadvantages of toxicity, potential flammability and instability. The zinc amalgam used in the Clemenson method has the defects of high toxicity and low safety. In addition, both of these methods have disadvantages of poor atomic economy and non-conformity to the concept of green chemistry. Therefore, it remains a challenge how to selectively remove specific oxygen atoms from biomass platform molecules. The method disclosed by the patent breakthroughs a system using metal triflate and a hydrogenation catalyst, selectively eliminates the ketocarbonyl group and retains the carboxyl group, and the 8-methylnonanoic acid is obtained in a green and efficient manner.
Disclosure of Invention
Based on the technical problems in the background art, the invention provides a method for preparing dihydrocapsaicin and dihydrocapsaicin ester. The raw materials of the invention are all derived from biomass resources and downstream products thereof, the invention has the advantages of good atom economy, high product yield, high product purity, little environmental pollution, simple process route and convenient operation, and is suitable for industrialized large-scale production.
The invention provides a method for preparing dihydrocapsaicin and dihydrocapsaicin ester, which comprises the following steps: (1) condensing furfural and methyl isopropyl ketone under an alkaline condition to obtain a condensation product A; (2) the condensation product A is subjected to ring opening in water or alcohol under acidic conditions to obtain 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate; (3) hydrogenating and deoxidizing 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate, hydrogen, trifluoromethanesulfonate and a hydrogenation catalyst to obtain 8-methyl nonanoic acid; (4) 8-methyl nonanoic acid reacts with vanillylamine or vanillyl alcohol under the action of a catalyst to generate dihydrocapsaicin or dihydrocapsaicin ester.
The synthetic route of the invention is as follows:
preferably, the pH under alkaline conditions is from 9 to 14.
Preferably, alkaline conditions are maintained with an alkaline substance.
Preferably, the alkaline substance is an alkaline substance containing a metal element.
Preferably, the basic substance is selected from metal hydroxides, metal carbonates, metal bicarbonates or metal alkoxides, for example alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates or alkali metal alkoxides.
Preferably, the alkaline substance includes, but is not limited to, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium ethoxide, potassium tert-butoxide and other conventional alkaline substances containing metal elements.
Preferably, the molar ratio of basic material to methyl isopropyl ketone is from 0.01:1 to 0.2: 1.
Preferably, the molar ratio of furfural to methyl isopropyl ketone is from 1:1 to 1: 5.
Preferably, the specific steps of condensing furfural with methyl isopropyl ketone are as follows: uniformly mixing an alkaline substance and a methyl isopropyl ketone solution, dropwise adding a furfural solution, reacting for 2-24h, and then acidifying to obtain a condensation product A.
Preferably, the reaction temperature is 10-150 ℃;
preferably, in the condensation step, the solvent of the methyl isopropyl ketone solution is water, methanol or ethanol.
Preferably, in the condensation step, the solvent of the furfural solution is methanol or ethanol.
Preferably, in the condensation step, acidification is performed with an acidic aqueous solution.
Preferably, in the condensation step, the acidic aqueous solution is an aqueous solution of an inorganic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, carbonic acid, or the like, in a mass fraction of 5 to 10% by weight.
Preferably, in the condensation step, acidification is followed by purification to give condensation product A.
Preferably, the specific steps for purifying the condensation product a are: drying, filtering to obtain filtrate, and distilling under reduced pressure to obtain condensation product A.
Preferably, the pH of the acidic conditions is less than 1.
Preferably, the acidic conditions are maintained with an acidic substance.
Preferably, the acidic substance is a strong inorganic acid.
Preferably, the strong inorganic acid includes, but is not limited to, hydrochloric acid, sulfuric acid, and the like, which are conventional strong inorganic acids.
Preferably, the specific steps of ring opening of the condensation product a are: mixing water or alcohol and condensation product A, adjusting pH to less than 1, refluxing, and spin-drying to obtain liquid, i.e. 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate.
Preference is given toThe alcohol used in the ring-opening step is an alkanol, preferably C1-30Alkanol, more preferably C1-20Alkanol, more preferably C1-12Alkanol, more preferably C1-6Alkanols (e.g. methanol, ethanol, propanol, butanol, pentanol and hexanol).
Preferably, the 4, 7-diketo-8-methylnonanoate is an alkyl 4, 7-diketo-8-methylnonanoate, such as 4, 7-diketo-8-methylnonanoate C1-30Alkyl esters, e.g. 4, 7-diketo-8-methylnonanoic acid C1-20Alkyl esters, e.g. 4, 7-diketo-8-methylnonanoic acid C1-12Alkyl esters, e.g. 4, 7-diketo-8-methylnonanoic acid C1-6Alkyl esters (e.g., methyl, ethyl, propyl, butyl, pentyl, and hexyl esters).
In the above ring-opening process, the amount of water or alcohol is not specified, and the amount is determined according to the specific operation.
Preferably, in the ring opening step, the pH is adjusted to less than 1 with an aqueous solution of an acidic substance.
Preferably, the mass fraction of the aqueous acidic substance solution is 10 to 50% by weight.
Preferably, in the ring opening step, reflux is carried out for 2-24 h.
Preferably, in the ring opening step, the reaction temperature is 100-150 ℃.
Preferably, in the ring opening step, after spin-drying, purification is carried out again to obtain 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate.
Preferably, the specific steps for purifying the 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate are as follows: dissolving the liquid obtained by spin-drying in alkaline aqueous solution of sodium hydroxide, sodium bicarbonate, potassium bicarbonate, sodium carbonate or potassium carbonate, adding activated carbon for decolorization, filtering to obtain filtrate, adding dilute hydrochloric acid or dilute sulfuric acid to adjust pH to less than 1, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate.
Preferably, in the hydrodeoxygenation step, the triflate is a metal triflate having a valence of from +1 to + 6.
Preferably, the molar ratio of 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoate to the metal triflate is from 10:1 to 1000: 1; preferably, the molar ratio of 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoate to triflate is from 10:1 to 100: 1.
Preferably, the triflate salt includes, but is not limited to, W (OTf)6、Zr(OTf)4、Al(OTf)3、Sc(OTf)3、Nb(OTf)5、Cu(OTf)2、Sc(OTf)2、Hf(OTf)4AgOTf, etc., metal triflates having a valence of from 1 to + 6.
Preferably, the hydrogenation catalyst is a catalyst comprising a group VIII transition metal element.
Preferably, the molar ratio of the metal element in the group VIII transition metal element-containing catalyst to the 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoate is from 1:10 to 1: 1000.
The hydrogenation catalyst refers to a catalyst used in the addition of a compound and hydrogen, such as a group VIII transition metal, a metal oxide containing a group VIII transition metal element, a metal complex containing a group VIII transition metal element, and the like; the support for the metal complex is typically alumina or activated carbon; specific hydrogenation catalysts include, but are not limited to: palladium on carbon, platinum on carbon, ruthenium on carbon, and the like.
Preferably, the reaction solvent in the hydrodeoxygenation step is a carboxylic acid or an alkane (e.g., C)1-12Carboxylic acid or alkane).
Preferably, the reaction solvent in the hydrodeoxygenation step is acetic acid or n-octane.
Preferably, the reaction solvent in the hydrodeoxygenation step is acetic acid.
In the above hydrodeoxygenation process, the amount of the reaction solvent is not specified, and is determined according to the specific operation.
Preferably, the hydrogen pressure in the hydrodeoxygenation step is from 1 to 50 atm.
Preferably, the hydrogen pressure in the hydrodeoxygenation step is from 2 to 10 atm.
Preferably, the reaction temperature in the hydrodeoxygenation step is 100-250 ℃.
Preferably, the reaction temperature in the hydrodeoxygenation step is 160-200 ℃.
Preferably, the reaction time in the hydrodeoxygenation step is between 10min and 24 h.
Preferably, the reaction time in the hydrodeoxygenation step is between 30min and 3 h.
Preferably, the hydrodeoxygenation comprises the following specific steps: uniformly mixing 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate, a hydrogenation catalyst, trifluoromethanesulfonate and a reaction solvent, stirring and heating in a hydrogen atmosphere, and stirring at a constant temperature to obtain 8-methylnonanoic acid.
Preferably, in the hydrodeoxygenation step, after stirring at a constant temperature, the mixture is purified to obtain 8-methylnonanoic acid.
Preferably, the specific steps for purifying 8-methylnonanoic acid are: filtering to obtain a filtrate, adjusting the pH value of the reaction solution to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid.
Preferably, the preparation method further comprises recycling of the metal triflate and the hydrogenation catalyst.
Preferably, the recycling comprises the steps of: separating 8-methylnonanoic acid from the reaction liquid, and adding 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate again for hydrodeoxygenation reaction.
In the step (4), the specific steps of synthesizing the dihydrocapsaicin or the dihydrocapsaicin ester are as follows: mixing 8-methylnonanoic acid, vanillylamine or vanillyl alcohol, a catalyst and a reaction solvent uniformly, carrying out reflux reaction in a nitrogen atmosphere, and carrying out spin drying after the reaction is finished to obtain the dihydrocapsaicin or dihydrocapsaicin ester.
Preferably, the catalyst used in step (4) is selected from 4-Dimethylaminopyridine (DMAP) and 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) or Dicyclohexylcarbodiimide (DCC).
Preferably, the reaction temperature in step (4) is 0 to 100 ℃.
Preferably, the reaction time in step (4) is 4 to 48 hours.
Preferably, n-octane, dichloromethane or toluene is used as the reaction solvent in step (4).
Preferably, the specific steps of purifying the dihydrocapsaicin or dihydrocapsaicin ester are as follows: adding deionized water for washing, adding chloroform for extraction, drying the extract and then spin-drying.
In the processes of condensation, ring opening, hydrodeoxygenation and synthesis of the target product, the completion of the reaction can be monitored by thin-layer chromatography.
The inventor of the invention has intensively studied and found that condensation product A (1- (2-furyl) -1-pentene-4-methyl-3-one) is subjected to ring opening in water or alcohol under acidic conditions to obtain 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate, and after a ketone carbonyl in 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate is hydrogenated to be converted into a secondary alcohol hydroxyl group, the secondary alcohol hydroxyl group is easily reacted with carboxylic acid to obtain a secondary alcohol ester under the promotion of trifluoromethanesulfonate; the secondary alcohol ester can remove hydroxyl by hydrogenolysis under the promotion of the triflate, so that the 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate can be selectively hydrodeoxygenated to obtain 8-methyl nonanoic acid under the co-catalysis of a hydrogenation catalyst and the triflate; 8-methyl nonanoic acid reacts with vanillylamine and vanillyl alcohol under the action of a catalyst to obtain dihydrocapsaicin and dihydrocapsaicin ester. The method has the advantages of good atomic economy, high product yield, high product purity, small environmental pollution, simple process route, convenient operation, suitability for industrial large-scale production, wide application field of the products dihydrocapsaicin and dihydrocapsaicin ester and good market prospect. The invention has potential industrial application prospect, and selects furfural, methyl isopropyl ketone, vanillyl amine and vanillyl alcohol as raw materials to prepare a target product, wherein the furfural can be obtained by hydrolyzing hemicellulose, the methyl isopropyl ketone can be obtained by hydrolyzing or alcoholyzing cellulose, and the vanillyl alcohol and the vanillyl amine can be obtained by hydrolyzing lignin. Therefore, the raw materials of the invention have wide sources, are renewable biomass resources, are cheap and easy to obtain, have simple operation, reduce the production cost and are suitable for industrial production.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of dihydrocapsaicin prepared according to the invention.
FIG. 2 is a nuclear magnetic carbon spectrum of the dihydrocapsaicin prepared by the invention.
FIG. 3 is a nuclear magnetic hydrogen spectrum of the dihydrocapsaicine ester prepared by the invention.
FIG. 4 is the nuclear magnetic carbon spectrum of the dihydrocapsaicine ester prepared by the invention.
FIG. 5 is the nuclear magnetic hydrogen spectrum of 8-methyl pelargonic acid prepared by the invention.
FIG. 6 is the nuclear magnetic carbon spectrum of 8-methylnonanoic acid prepared by the method.
FIG. 7 is a nuclear magnetic hydrogen spectrum of 4, 7-diketone-8-methylnonanoic acid prepared by the method.
FIG. 8 is the nuclear magnetic carbon spectrum of 4, 7-diketone-8-methyl nonanoic acid prepared by the invention.
FIG. 9 is a nuclear magnetic hydrogen spectrum of 1- (2-furyl) -1-penten-4-methyl-3-one prepared by the invention.
FIG. 10 is the nuclear magnetic carbon spectrum of 1- (2-furyl) -1-penten-4-methyl-3-one prepared by the invention.
FIG. 11 is a nuclear magnetic hydrogen spectrum of methyl 4, 7-dione-8-methylnonanoate prepared by the present invention.
FIG. 12 is the nuclear magnetic carbon spectrum of methyl 4, 7-diketone-8-methylnonanoate prepared by the invention.
Detailed Description
The metal triflates used in this experiment were purchased from Adamas reagent, Inc. (Adamas), ruthenium on carbon, palladium on carbon, and platinum on carbon were purchased from Alfa Aesar, chemical Co., Ltd., DMAP, EDC, and DCC were purchased from Shanghai Arlatin Biotechnology Ltd., and the other reagents were purchased from the national pharmaceutical group.
For the purpose of facilitating an understanding of the present invention, the present invention will now be described by way of examples. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
Uniformly mixing sodium hydroxide and a methyl isopropyl ketone aqueous solution, dropwise adding a furfural methanol solution, reacting for 11 hours at 35 ℃, acidifying with a 5 wt% hydrochloric acid aqueous solution, drying, filtering to obtain a filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-penten-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 5:3, and the molar ratio of sodium hydroxide to methyl isopropyl ketone is 0.05: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 96%.
Uniformly mixing methanol and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using 20 wt% hydrochloric acid aqueous solution, refluxing for 24 hours at 100 ℃, and spin-drying to obtain liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain methyl 4, 7-diketone-8-methylnonanoate with yield of 82%.
Methyl 4, 7-dione-8-methylnonanoate, platinum carbon, Zr (OTf)4Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 30atm) to raise temperature to 180 deg.C, stirring for 1h, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid methyl ester is reacted with Zr (OTf)4The molar ratio of the platinum element in the platinum carbon to the methyl 4, 7-diketone-8-methylnonanoate is 1: 10. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 88% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillylamine, DMAP, EDC and n-octane, stirring and heating to 90 ℃ in a nitrogen atmosphere, preserving heat for 15 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicin was determined by High Purity Liquid Chromatography (HPLC) and had a purity of 98%.
The nuclear magnetic hydrogen spectrum of the dihydrocapsaicin is shown in figure 1; the nuclear magnetic carbon spectrum of the dihydrocapsaicin is shown in figure 2.
The nuclear magnetic hydrogen spectrum of 8-methylnonanoic acid is shown in FIG. 5; the nuclear magnetic carbon spectrum of 8-methylnonanoic acid is shown in FIG. 6.
The nuclear magnetic hydrogen spectrum of the 1- (2-furyl) -1-penten-4-methyl-3-ketone is shown in figure 9; the nuclear magnetic carbon spectrum of 1- (2-furyl) -1-penten-4-methyl-3-one is shown in figure 10.
The nuclear magnetic hydrogen spectrum of the 4, 7-diketone-8-methyl nonanoate is shown in FIG. 11; the nuclear magnetic carbon spectrum of the 4, 7-diketone-8-methyl nonanoate is shown in figure 12.
Example 2
Uniformly mixing sodium hydroxide and a methyl isopropyl ketone aqueous solution, dropwise adding a furfural methanol solution, reacting for 15h at 25 ℃, acidifying with a 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain a filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-penten-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 2:1, and the molar ratio of sodium hydroxide to methyl isopropyl ketone is 0.05: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 95%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a hydrochloric acid aqueous solution with the mass fraction of 5 wt%, refluxing for 20 hours at 110 ℃, and spin-drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 83%.
4, 7-diketone-8-methyl nonanoic acid, platinum carbon, Sc (OTf)3Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure is 40atm), heating to 120 deg.C, stirring for 4 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with Sc (OTf)3The molar ratio of the platinum element in the platinum carbon to the 4, 7-diketone-8-methylnonanoic acid is 1: 20. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 86% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillyl alcohol, DMAP, EDC and toluene, stirring and heating to 70 ℃ in a nitrogen atmosphere, preserving heat for 10 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicine ester was measured by High Purity Liquid Chromatography (HPLC) to have a purity of 92%.
The nuclear magnetic hydrogen spectrum of the dihydrocapsaicine ester is shown in figure 3; the nuclear magnetic carbon spectrum of the dihydrocapsaicine ester is shown in figure 4.
The nuclear magnetic hydrogen spectrum of the 4, 7-diketone-8-methylnonanoic acid is shown in FIG. 7; the nuclear magnetic carbon spectrum of the 4, 7-diketone-8-methylnonanoic acid is shown in FIG. 8.
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of 8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 1.
Example 3
Uniformly mixing sodium hydroxide and methyl isopropyl ketone methanol solution, dropwise adding furfural methanol solution, reacting for 12h at 25 ℃, acidifying by hydrochloric acid aqueous solution with the mass fraction of 10 wt%, filtering after drying to obtain filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-penten-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 1.2:1, and the molar ratio of sodium hydroxide to methyl isopropyl ketone is 0.02: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 93%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a sulfuric acid aqueous solution with the mass fraction of 20 wt%, refluxing for 5 hours at 100 ℃, and spin-drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 83%.
4, 7-diketone-8-methyl nonanoic acid, palladium carbon, Sc (OTf)3Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 30atm), heating to 200 deg.C, stirring for 3 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with Sc (OTf)3The molar ratio of the palladium element in the palladium carbon to the 4, 7-diketone-8-methylnonanoic acid is 1: 10. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 88% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillylamine, DMAP, DCC and n-octane, stirring and heating to 70 ℃ in a nitrogen atmosphere, preserving heat for 24 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicin was measured by High Purity Liquid Chromatography (HPLC) and had a purity of 96%.
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of the dihydrocapsaicin are consistent with those of example 1. The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 2.
Example 4
Uniformly mixing sodium hydroxide and a methyl isopropyl ketone aqueous solution, dropwise adding a furfural methanol solution, reacting for 15 hours at 15 ℃, acidifying with a 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain a filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-pentene-4-methyl-3-ketone, wherein the molar ratio of the methyl isopropyl ketone to the furfural is 2:1, and the molar ratio of the sodium hydroxide to the methyl isopropyl ketone is 0.05: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 96%.
Uniformly mixing methanol and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a sulfuric acid aqueous solution with the mass fraction of 10 percent, refluxing for 10 hours at 110 ℃, and spin-drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain methyl 4, 7-diketone-8-methylnonanoate with yield of 84%.
4, 7-diketone-8-methyl nonanoic acid methyl ester, platinum carbon, Sc (OTf)3Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 20atm) to 160 deg.C, stirring for 24 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid methyl ester is reacted with Sc (OTf)3The molar ratio of the platinum element in the platinum carbon to the methyl 4, 7-diketone-8-methylnonanoate is 1: 20. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 84% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillyl alcohol, DMAP, EDC and dichloromethane, stirring and heating to 90 ℃ in a nitrogen atmosphere, preserving heat for 12 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicine ester was determined to have a purity of 98% by High Purity Liquid Chromatography (HPLC).
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of the dihydrocapsaicine ester are consistent with those of example 2. The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid methyl ester and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 1.
Example 5
Uniformly mixing sodium bicarbonate and a methyl isopropyl ketone aqueous solution, dropwise adding a furfural methanol solution, reacting for 15h at 35 ℃, acidifying with a 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain a filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-penten-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 2:1, and the molar ratio of sodium bicarbonate to methyl isopropyl ketone is 0.05: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 94%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a sulfuric acid aqueous solution with the mass fraction of 15 wt%, refluxing for 20 hours at 105 ℃, and spin-drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 81%.
4, 7-diketone-8-methyl nonanoic acid, platinum carbon, Sc (OTf)3Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 20atm) to 150 deg.C, stirring for 24 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with Sc (OTf)3The molar ratio of the platinum element in the platinum carbon to the 4, 7-diketone-8-methylnonanoic acid is 1: 20. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 85% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillyl alcohol, DMAP, DCC and n-octane, stirring and heating to 30 ℃ in a nitrogen atmosphere, preserving heat for 7 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicine ester was determined to have a purity of 97% by High Purity Liquid Chromatography (HPLC).
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of dihydrocapsaicinoid, 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one were in accordance with example 2.
Example 6
Uniformly mixing sodium hydroxide and a methyl isopropyl ketone aqueous solution, dropwise adding a furfural methanol solution, reacting for 3 hours at 85 ℃, acidifying with a hydrochloric acid aqueous solution with the mass fraction of 10 wt%, drying, filtering to obtain a filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-pentene-4-methyl-3-ketone, wherein the molar ratio of the methyl isopropyl ketone to the furfural is 2:1, and the molar ratio of the sodium hydroxide to the methyl isopropyl ketone is 0.1: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 95%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using 20 wt% hydrochloric acid aqueous solution, refluxing for 15h at 115 ℃, and spin-drying to obtain liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 82%.
4, 7-diketone-8-methyl nonanoic acid, platinum carbon, Hf (OTf)4Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 20atm) to 190 deg.C, stirring for 24 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with Hf (OTf)4The molar ratio of the platinum element in the platinum carbon to the 4, 7-diketone-8-methylnonanoic acid is 1: 20. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 88% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillylamine, DMAP, EDC and dichloromethane, stirring and heating to 50 ℃ in a nitrogen atmosphere, preserving heat for 36 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicin was measured by High Purity Liquid Chromatography (HPLC) and had a purity of 99%.
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of dihydrocapsaicin, 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 3.
Example 7
Uniformly mixing sodium ethoxide and methyl isopropyl ketone aqueous solution, dropwise adding furfural methanol solution, reacting at 20 ℃ for 10h, acidifying with 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-pentene-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 2:1, and the molar ratio of sodium ethoxide to methyl isopropyl ketone is 0.08: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 95%.
Uniformly mixing methanol and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a hydrochloric acid aqueous solution with the mass fraction of 13 percent, refluxing for 10 hours at 120 ℃, and spin-drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain methyl 4, 7-diketone-8-methylnonanoate with yield of 84%.
Uniformly mixing 4, 7-diketone-8-methyl nonanoic acid methyl ester, ruthenium carbon, AgOTf and acetic acid, stirring and heating to 170 ℃ in a hydrogen atmosphere (the hydrogen pressure is 20atm), keeping the temperature and stirring for 2h, filtering to obtain a filtrate, adjusting the pH of the reaction solution to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and then distilling under reduced pressure to obtain 8-methyl nonanoic acid. Wherein the molar ratio of the 4, 7-diketone-8-methyl nonanoate to AgOTf is 50:1, and the molar ratio of the ruthenium element in the ruthenium carbon to the 4, 7-diketone-8-methyl nonanoate is 1: 100. The yield of methyl 8-methylnonanoate, determined by Gas Chromatography (GC), was 90% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillyl alcohol, DMAP, EDC and dichloromethane, stirring and heating to 100 ℃ in a nitrogen atmosphere, preserving heat for 7 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicine ester was determined to have a purity of 98% by High Purity Liquid Chromatography (HPLC).
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of dihydrocapsaicinoid, 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoate, and 1- (2-furyl) -1-penten-4-methyl-3-one were in accordance with example 4.
Example 8
Uniformly mixing sodium hydroxide and methyl isopropyl ketone methanol solution, dropwise adding furfural methanol solution, reacting at 10 ℃ for 12 hours, acidifying with 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain filtrate, and distilling under reduced pressure to obtain a product 1- (2-furyl) -1-pentene-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 2:1, and the molar ratio of sodium hydroxide to methyl isopropyl ketone is 0.02: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 93%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using 17 wt% hydrochloric acid aqueous solution, refluxing for 15h at 110 ℃, and spin-drying to obtain liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 82%.
4, 7-diketone-8-methyl nonanoic acid, palladium carbon, Al (OTf)3Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 30atm) to 150 deg.C, stirring for 3 hr, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with Hf (OTf)4The molar ratio of the palladium element to the 4, 7-diketone-8-methylnonanoic acid in the palladium-carbon is 75:1, and the molar ratio of the palladium element to the 4, 7-diketone-8-methylnonanoic acid is 1: 25. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 96% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillylamine, DMAP, EDC and toluene, stirring and heating to 60 ℃ in a nitrogen atmosphere, preserving heat for 8 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicin was determined by High Purity Liquid Chromatography (HPLC) and had a purity of 97%.
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of dihydrocapsaicin, 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 3.
Example 9
Uniformly mixing sodium hydroxide and methyl isopropyl ketone methanol solution, dropwise adding furfural methanol solution, reacting at 30 ℃ for 20 hours, acidifying with 10 wt% hydrochloric acid aqueous solution, drying, filtering to obtain filtrate, and carrying out reduced pressure distillation to obtain a product 1- (2-furyl) -1-pentene-4-methyl-3-ketone, wherein the molar ratio of methyl isopropyl ketone to furfural is 2:1, and the molar ratio of sodium hydroxide to methyl isopropyl ketone is 0.1: 1. The yield of 1- (2-furyl) -1-penten-4-methyl-3-one was 95%.
Uniformly mixing water and 1- (2-furyl) -1-pentene-4-methyl-3-ketone, adjusting the pH to be less than 1 by using a hydrochloric acid aqueous solution with the mass fraction of 10 percent, carrying out reflux reaction for 10 hours at 105 ℃, and carrying out spin drying to obtain a liquid; dissolving the liquid in 10 wt% sodium hydroxide water solution, adding activated carbon, heating for decolorizing, filtering to obtain filtrate, adjusting pH to less than 1 with hydrochloric acid, and crystallizing to obtain 4, 7-diketone-8-methylnonanoic acid with yield of 80%.
4, 7-diketone-8-methyl nonanoic acid, palladium carbon, W (OTf)6Mixing with acetic acid, stirring in hydrogen atmosphere (hydrogen pressure of 30atm) to raise temperature to 180 deg.C, stirring for 3h, filtering to obtain filtrate, adjusting pH to 7, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and distilling under reduced pressure to obtain 8-methylnonanoic acid. Wherein 4, 7-diketo-8-methylnonanoic acid is reacted with W (OTf)6The molar ratio of the palladium element to the 4, 7-diketone-8-methylnonanoic acid in the palladium-carbon is 25:1, and the molar ratio of the palladium element to the 4, 7-diketone-8-methylnonanoic acid is 1: 25. The yield of 8-methylnonanoic acid, determined by Gas Chromatography (GC), was 90% with a purity of 99%.
Uniformly mixing 8-methylnonanoic acid, vanillylamine, DMAP, DCC and dichloromethane, stirring and heating to 25 ℃ in a nitrogen atmosphere, preserving heat for 15 hours, cooling to room temperature, adding deionized water for washing, adding chloroform for extraction, drying the extract, and then spin-drying. The obtained dihydrocapsaicin was measured by High Purity Liquid Chromatography (HPLC) and had a purity of 99%.
The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum of dihydrocapsaicin, 8-methylnonanoic acid, 4, 7-dione-8-methylnonanoic acid and 1- (2-furyl) -1-penten-4-methyl-3-one are in accordance with example 3.
The present invention is described in detail with reference to the drawings, and the accompanying drawings, wherein the description is given by way of illustration and example only, and not by way of limitation.
Claims (37)
1. A method of preparing dihydrocapsaicin or a dihydrocapsaicin ester, comprising the steps of:
(1) condensing furfural and methyl isopropyl ketone under an alkaline condition to obtain a condensation product;
(2) opening the ring of the condensation product in water or alcohol under acidic conditions to obtain 4, 7-diketone-8-methyl nonanoic acid or 4, 7-diketone-8-methyl nonanoate;
(3) hydrogenating and deoxidizing 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate, hydrogen, metal triflate and a hydrogenation catalyst to obtain 8-methylnonanoic acid;
(4) 8-methyl nonanoic acid is reacted with vanillylamine or vanillyl alcohol to form dihydrocapsaicin or dihydrocapsaicin esters.
2. The method according to claim 1, wherein in step (1), the alkaline condition has a pH of 9 to 14.
3. The method of claim 2, wherein the alkaline condition is maintained with an alkaline substance.
4. A process according to claim 3, characterized in that the basic substance is selected from metal hydroxides, metal carbonates, metal bicarbonates or metal alkoxides.
5. A process according to claim 3, characterized in that the basic substance is selected from alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates or alkali metal alkoxides.
6. The method of claim 3, wherein the alkaline substance is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium ethoxide, and potassium tert-butoxide.
7. The method according to claim 1, wherein in the step (1), the specific steps of condensing the furfural with methyl-isopropyl-ketone are as follows: and (3) uniformly mixing the alkaline substance with the methyl isopropyl ketone solution, dripping the furfural solution, and acidifying to obtain a condensation product.
8. The process of claim 7, wherein the molar ratio of furfural to methyl isopropyl ketone is from 1:1 to 1: 5.
9. The process according to claim 7, wherein in step (1), the molar ratio of the basic substance to methyl isobutyl ketone is from 0.01:1 to 0.2: 1.
10. The method of claim 7, wherein the solvent of the methyl isopropyl ketone solution is water, methanol or ethanol.
11. The method according to claim 7, wherein the solvent of the furfural solution is methanol or ethanol.
12. The process according to claim 7, wherein the reaction temperature is 10 to 150 ℃.
13. The process according to claim 7, wherein the reaction time is 2 to 24 hours.
14. The method according to claim 1, wherein in step (2), the pH of the acidic condition is less than 1.
15. The method of claim 14, wherein the acidic condition is maintained with an acidic substance.
16. The method of claim 14, wherein the acidic material is a strong inorganic acid.
17. The method of claim 16, wherein the strong inorganic acid comprises hydrochloric acid and sulfuric acid.
18. The method according to claim 1, wherein in step (2), the specific steps of ring opening of the condensation product are: and (3) uniformly mixing the condensation product with water or alcohol, adjusting the pH to be less than 1, refluxing, and spin-drying to obtain 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate.
19. The method of claim 18, wherein in step (2), the pH is adjusted to less than 1 with an aqueous acidic material solution.
20. The method of claim 18, wherein the reflux time is 2-24 hours.
21. The method as claimed in claim 18, wherein the reaction temperature is 100-150 ℃.
22. The process of claim 1, wherein in step (3), the hydrogenation catalyst is a catalyst containing a group VIII transition metal element.
23. The method of claim 22, wherein the hydrogenation catalyst is selected from palladium on carbon, platinum on carbon, and ruthenium on carbon.
24. The process of claim 22, wherein the molar ratio of the metal element in the hydrogenation catalyst to the 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoate is from 1:10 to 1: 1000.
25. The method according to claim 1, wherein the metal valence of the metal triflate is +1 to + 6.
26. The method of claim 1, wherein the metal triflate is W (OTf)6、Zr(OTf)4、Al(OTf)3、Sc(OTf)3、Nb(OTf)5、Cu(OTf)2、Sc(OTf)2、Hf(OTf)4And AgOTf.
27. The process according to claim 1, characterized in that the molar ratio of 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoic acid ester to the metal triflate is from 10:1 to 1000: 1.
28. The process according to claim 1, characterized in that the molar ratio of 4, 7-diketo-8-methylnonanoic acid or 4, 7-diketo-8-methylnonanoic acid ester to the metal triflate is from 10:1 to 100: 1.
29. The method according to claim 1, wherein in the step (3), the specific steps of hydrodeoxygenation are: uniformly mixing 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate, a hydrogenation catalyst, a metal trifluoromethanesulfonate and a reaction solvent, stirring and heating in a hydrogen atmosphere, and stirring at a constant temperature to obtain 8-methylnonanoic acid.
30. The method of claim 29, wherein the hydrogen pressure is 1-50 atm.
31. The method as claimed in claim 29, wherein the reaction temperature is 100-250 ℃.
32. The method of claim 29, wherein the reaction time is from 10min to 24 hours.
33. The process of claim 29, wherein the reaction solvent is a carboxylic acid or an alkane.
34. The process of claim 29, wherein the reaction solvent is acetic acid or n-octane.
35. The process of claim 1, wherein in step (3), the process further comprises recycling the metal triflate and the hydrogenation catalyst.
36. The method of claim 35, wherein said recycling comprises the steps of: separating 8-methylnonanoic acid from the reaction liquid, and adding 4, 7-diketone-8-methylnonanoic acid or 4, 7-diketone-8-methylnonanoate again for hydrodeoxygenation reaction.
37. The method as claimed in claim 1, wherein in the step (4), the specific steps of synthesizing the dihydrocapsaicin or dihydrocapsaicin ester are as follows: uniformly mixing 8-methylnonanoic acid, vanillylamine or vanillyl alcohol, 4-Dimethylaminopyridine (DMAP) and 1-ethyl- (3-dimethylaminopropyl) carbodiimide (EDC) or Dicyclohexylcarbodiimide (DCC) serving as catalysts, taking n-octane, dichloromethane and toluene as reaction solvents, carrying out reflux reaction in a nitrogen atmosphere, and after the reaction is finished, carrying out spin drying to obtain the dihydrocapsaicin or dihydrocapsaicin ester; the reaction temperature is 0-100 ℃; the reaction time is 4-48 hours.
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| JPS51113836A (en) * | 1975-03-28 | 1976-10-07 | San Ei Chem Ind Ltd | Preparation of dihydrocapasaicine |
| KR20090016804A (en) * | 2007-08-13 | 2009-02-18 | 주식회사 티지 바이오텍 | Novel benzyl ester compounds and the composition comprising the same for preventing and treating of obesity, diabetes and hyperlipidemia |
| CN104447383A (en) * | 2014-11-21 | 2015-03-25 | 中国农业科学院油料作物研究所 | Dihydrocapsaicin artificial hapten and artificial antigen as well as preparation methods thereof |
| CN107382712A (en) * | 2017-08-31 | 2017-11-24 | 合肥利夫生物科技有限公司 | A kind of preparation method of 1,10 decanedioic acid |
| CN110305031A (en) * | 2019-07-03 | 2019-10-08 | 刘晓珍 | The preparation method of capsaicine and the capsaicine being prepared using this method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20180101445A (en) * | 2016-01-07 | 2018-09-12 | 코나겐 인크. | Method for producing capcinoid by biosynthesis process |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS51113836A (en) * | 1975-03-28 | 1976-10-07 | San Ei Chem Ind Ltd | Preparation of dihydrocapasaicine |
| KR20090016804A (en) * | 2007-08-13 | 2009-02-18 | 주식회사 티지 바이오텍 | Novel benzyl ester compounds and the composition comprising the same for preventing and treating of obesity, diabetes and hyperlipidemia |
| CN104447383A (en) * | 2014-11-21 | 2015-03-25 | 中国农业科学院油料作物研究所 | Dihydrocapsaicin artificial hapten and artificial antigen as well as preparation methods thereof |
| CN107382712A (en) * | 2017-08-31 | 2017-11-24 | 合肥利夫生物科技有限公司 | A kind of preparation method of 1,10 decanedioic acid |
| CN110305031A (en) * | 2019-07-03 | 2019-10-08 | 刘晓珍 | The preparation method of capsaicine and the capsaicine being prepared using this method |
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