A method for preparing piperonal

Abstract

The present application relates to a kind of preparation methods of piperonal, which uses piperonal, glyoxylic acid as raw material, sulfuric acid-methanesulfonic acid mixed acid as catalyst to prepare 3,4-methylenedioxyphenyl glycol acid intermediate, then sulfuric acid-silica gel-nitric acid is used as oxidation system to decarboxylate oxidation and obtain piperonal.3,4-methylenedioxyphenyl glycol acid is prepared by using sulfuric acid-methanesulfonic acid mixed acid catalysis, which has the advantages of mild reaction condition, complete reaction product, and reaction process is not easy to stick together and the like.3,4-methylenedioxyphenyl glycol acid is prepared by using sulfuric acid-silica gel-nitric acid oxidation system to decarboxylate oxidation and obtain piperonal, which has the characteristics of reducing single nitric acid oxidation reaction intensity, less by-product, impurities easy to separate, high purity.The present application has the advantages of mild reaction, controllable process, less by-product, easy to separate, high purity, high yield, which can greatly reduce production cost, and is suitable for large-scale industrial production.

Description

Technical Field

[0001] This invention relates to a method for preparing piperine, belonging to the field of chemical synthesis technology. Technical Background

[0002] Piperaldehyde (as shown in the formula below) is an important chemical raw material widely used in the synthesis of cosmetics, pharmaceuticals, pesticides, and metal electroplating. The traditional preparation method for piperaldehyde involves isomerization and oxidation of safrole, an extract from plants. This traditional method is limited by natural safrole resources, has a lengthy preparation process, high costs, and causes serious environmental pollution, making it unsuitable for large-scale industrial production and failing to meet market demand. Chemical synthesis of piperaldehyde offers several advantages over preparation from natural sources and has become a research hotspot.

[0003]

[0004] Molecular formula: C8H6O3 Molecular weight: 150.13

[0005] According to literature reports, there are multiple synthetic routes for the chemical synthesis of piperine, most of which use piperine rings as raw materials, which are briefly described below.

[0006] Method 1: Chloromethylation followed by oxidation and hydrolysis synthesis.

[0007] Piperyl benzyl chloride is prepared by reacting a piperonyl ring with the potassium salt of 2-nitropropane in tert-butanol, yielding the product. The chemical reaction formula is as follows:

[0008]

[0009] The yield of this method is only about 50%, which is low and the cost is high.

[0010] Method 2: Synthesis via Sommelet reaction.

[0011] Piperaldehyde is obtained by salt and hydrolysis of piperine ring. The chemical reaction formula is:

[0012]

[0013] This route requires the reagents trioxymethylene and hexamethylenetetramine. In the presence of an oxidant, trioxymethylene releases vapor at high temperatures, which forms an explosive mixture with air, causing combustion and explosion. Hexamethylenetetramine is flammable and corrosive, and can cause burns to the human body. Contact can cause dermatitis. It is a dangerous reagent and is not conducive to safe production.

[0014] Method 3: Vilsmeiar formylation synthesis.

[0015] This method uses piperine as a raw material, and reacts it with N-methylformylaniline in the presence of phosphorus oxychloride or phosgene as a condensing agent to produce piperine. The chemical reaction formula is as follows:

[0016]

[0017] This method has a high yield, approximately 85-95%, but the source of N-methylformamide aniline is difficult to find, and recovery requires formic acid. Phosphorus oxychloride or phosgene easily causes environmental pollution, making its application and industrialization difficult.

[0018] Method 4: Synthesis by chloroacetaldehyde method.

[0019] Trichloroacetaldehyde is condensed in the presence of AlCl3 to produce trichloromethylbenzyl alcohol, which is then decarboxylated by hydrolysis to yield piperonal. The chemical reaction formula is:

[0020]

[0021] The anhydrous trichloroacetaldehyde used in this method is not easy to obtain. The reaction process is similar to that of the glyoxylic acid method, but the oxidation is carried out under alkaline conditions, and the oxidation effect of sulfuric acid is not as good as that of the glyoxylic acid method.

[0022] Method 5: Synthesis via glyoxylic acid method.

[0023] Piperaldehyde was synthesized from piperine rings and 50% glyoxylic acid. The chemical reaction formula is as follows:

[0024]

[0025] Patent reports on the preparation of piperaldehyde using the glyoxylic acid method mainly include:

[0026] CN1400972 discloses a method for preparing piperine, which consists of the following three consecutive steps: (A) an addition reaction step in which 1,2-methyldioxybenzene reacts with glyoxylic acid in the presence of a strong acid to generate 3,4-methyldioxymandelic acid; (B) an extraction step in which an organic solvent is added to the reaction solution, the reaction solution is then neutralized with an alkali, 3,4-methyldioxymandelic acid is extracted into the organic solvent layer, and the organic solvent layer is separated from the aqueous layer; (C) an oxidation reaction step in which the aqueous layer is removed, the organic solvent layer is concentrated, and nitric acid is added to the concentrate to react 3,4-methyldioxymandelic acid with nitric acid to generate piperine.

[0027] CN101324316A discloses a three-step method for preparing piperine, including:

[0028] The first step involves using 98% sulfuric acid as a catalyst, with a mass ratio of pepper rings to sulfuric acid of 1:0.21-0.22, to prepare 3,4-methylenedioxyphenylethanolic acid through reaction, separation, and purification.

[0029] The second step involves heating 3,4-methylenedioxyphenylethanolic acid and a 3.1% nitric acid solution for 4–6 minutes to carry out an oxidation reaction, yielding piperine oil.

[0030] The third step involves dissolving the obtained oily substance in dichloromethane, washing it with water, washing it with sodium bicarbonate water until neutral, drying it, concentrating it, and distilling it under reduced pressure to obtain the product piperonal.

[0031] It is particularly important to note in this invention that:

[0032] Compared to the five synthetic methods mentioned above, all have shortcomings. Among them, the glyoxylic acid method has the advantages of simple process and readily available raw materials. This method has two published patents. Both patents use sulfuric acid as a single strong acid catalyst to prepare the 3,4-methylenedioxyphenylethanolic acid intermediate and nitric acid as a single oxidant to prepare piperine. Both the one-pot method (CN1400972) without separate steps and the three-step method (CN101324316A) have two insurmountable defects.

[0033] Defect 1: Use of concentrated sulfuric acid alone. This acid is a viscous, strong oxidizing acid with dehydrating properties, while dilute sulfuric acid has virtually no catalytic activity. Experiments show that although concentrated sulfuric acid has good catalytic activity, it easily causes the reaction system to become viscous and clump, leading to incomplete reactions. In severe cases, it can cause stirring to stop, preventing the reaction from proceeding, resulting in unstable reactions, low yields, and compromised quality. Furthermore, mixing concentrated sulfuric acid with 50% glyoxylic acid generates a large amount of heat. Neither of the aforementioned patents employs pre-cooling, but instead directly controls the temperature of the reaction, inevitably leading to excessively high reaction temperatures. This makes it difficult to control the temperature within the effective low-temperature reaction time, causing the reaction to become viscous, clump, and reduce efficiency.

[0034] Defect 2: Use of single nitric acid. This acid is a strong oxidizing acid, and its oxidizing power is directly related to its concentration. Patent CN101324316A uses a low concentration of nitric acid (3.1%) to make the oxidation reaction relatively mild, but the oxidation time of 4-6 minutes is too short. Insufficient oxidizing power will lead to incomplete oxidation and reduced yield. Increasing the nitric acid concentration can promote a more complete oxidation reaction, but it will also result in a violent reaction, causing excessive by-products, making it difficult to separate the product from impurities, thus affecting quality and reducing yield. Summary of the Invention

[0035] The technical problem to be solved by this invention is to take advantage of the readily available raw materials and simple process of the glyoxylic acid method, while overcoming the shortcomings of existing patents that use sulfuric acid catalysis to prepare 3,4-methylenedioxyphenylethanolic acid intermediate and nitric acid oxidation to prepare piperine. This invention provides a method for preparing high-quality, high-yield products of 3,4-methylenedioxyphenylethanolic acid intermediate and piperine, which has a mild and stable reaction, does not easily cause the reactants to become viscous and agglomerated, produces fewer by-products, and allows for easy separation of products and impurities.

[0036] This invention relates to a process using piperine and 50% glyoxylic acid as raw materials. The detailed process involves mixing 98% sulfuric acid, 99% methanesulfonic acid, and 50% glyoxylic acid, pre-cooling to -10 to 0°C, adding piperine dropwise, catalyzing the reaction at 0 to 5°C for 2 to 4 hours, and then reacting at 10 to 30°C for 17 to 19 hours. After washing, filtering, and drying, a 3,4-methylenedioxyphenylglycolic acid intermediate is obtained. This intermediate is then oxidized and decarboxylated in a sulfuric acid-silica gel chromatography-5% nitric acid system at 75 to 85°C, followed by washing with hot water at 75 to 85°C until neutral, extraction with 4 to 6 times the amount of ethyl acetate, concentration under reduced pressure, crystallization with 5 to 8 times the amount of 50 to 75% ethanol, and filtration to obtain a crude product. The crude product is then recrystallized with 3 to 5 times the amount of 95% ethanol at -10 to 0°C, filtered, and dried to obtain high-purity piperine.

[0037] The technical solution of this invention is as follows:

[0038] A method for preparing piperine, the method comprising the following steps:

[0039] Step 1: Mix glyoxylic acid, sulfuric acid, and methanesulfonic acid, and pre-cool to a certain temperature;

[0040] Step 2: Add pepper rings dropwise, and react under controlled temperature conditions using sulfuric acid-methanesulfonic acid as a catalyst;

[0041] Step 3: 3,4-methylenedioxyphenylethanolic acid intermediate is obtained by washing and drying;

[0042] Step 4: The intermediate 3,4-methylenedioxyphenylethanolic acid is oxidized and decarboxylated using a sulfuric acid-silica gel chromatography-nitric acid oxidation system. After extraction with ethyl acetate, concentration, ethanol crystallization, and recrystallization, high-purity piperonal is obtained.

[0043] Preferably, the mass ratio of pepper rings: 50% glyoxylic acid: 98% sulfuric acid: 99% methanesulfonic acid is 1:1.57-1.77:1.37-1.57:0.05-0.07.

[0044] Preferably, in step 1, before the reaction, 50% glyoxylic acid, 98% sulfuric acid, and 99% methanesulfonic acid are mixed in proportion and then pre-cooled to -10 to 0°C.

[0045] Preferably, in step 2, pepper rings are added dropwise while the reaction temperature is controlled at 0–5°C. After the addition is complete, the reaction is carried out at 10–30°C for 2–4 hours and then continued for 17–19 hours.

[0046] Preferably, in step 3, the product is washed with tap water 3 to 5 times to neutralize the pH and then air-dried to obtain the 3,4-methylenedioxyphenylethanol intermediate.

[0047] Preferably, in step 4:

[0048] The mass ratio of the materials in the mixture of 3,4-methylenedioxyphenylethanolic acid, 98% sulfuric acid, silica gel, and 5% nitric acid is 1:0.1-0.3:0.1-0.3:5-8.

[0049] The temperature for preventing bumping during the oxidative decarboxylation process is 75–85°C.

[0050] After the reaction is complete, first pour off the upper layer of dilute acid solution, and then wash the lower layer of piperine and silica gel mixture three times with hot water at 75-85°C.

[0051] Based on 3,4-methylenedioxyphenylethanolic acid, the washed mixed oily substance was extracted three times with 4 to 6 times the amount of ethyl acetate to obtain an ethyl acetate extract containing piperonal.

[0052] The ethyl acetate extract was concentrated under reduced pressure to remove the solvent, yielding a red oily substance. This substance was dissolved in 5-8 times the amount of 50-75% ethanol and crystallized once at -10 to 0°C. The crude product was then dissolved again in 3-5 times the amount of 95% ethanol and recrystallized once at -10 to 0°C to obtain high-purity piperine.

[0053] The catalytic system of this invention is characterized by employing a sulfuric acid-methanesulfonic acid mixed acid catalytic system in the preparation of the 3,4-methylenedioxyphenylethanolic acid intermediate. This mixed acid catalysis has the following three advantages over single strong acid catalysis:

[0054] First, methanesulfonic acid is a water-soluble, non-oxidizing organic acid with catalytic function similar to sulfuric acid, but weaker than sulfuric acid. Using sulfuric acid and methanesulfonic acid can effectively coordinate and reduce the catalytic activity of sulfuric acid, making the reaction more stable and controllable.

[0055] Secondly, this mixed acid catalytic system can also reduce the heat release during the mixing process with glyoxylic acid, shorten the reaction precooling time, and then precool to -10 to 0°C after mixing with acid, and add pepper rings dropwise to ensure that the subsequent reaction temperature is effectively controlled.

[0056] Third, by controlling the reaction temperature from 0 to 5°C, the mixed acid catalytic system reacts more smoothly, does not become viscous during the reaction process, avoids reactant agglomeration, and ensures complete reaction. At the same time, methanesulfonic acid can be washed away with water after the reaction, which is environmentally friendly. The entire reaction is conducive to improving yield and reducing cost.

[0057] The oxidation system of this invention is characterized by employing a sulfuric acid-silica gel chromatography-nitric acid oxidation system. This oxidation system has the following two advantages over a single nitric acid oxidant:

[0058] Firstly, this oxidative decarboxylation system has an optimized combination of mass ratios and process conditions, which can make the oxidation reaction of 3,4-methylenedioxyphenylethanol acid more stable and thorough, and improve reaction efficiency.

[0059] Secondly, the adsorption effect of silica gel in chromatography helps the adsorption of by-products, making them easy to separate from piperine, resulting in piperine with high purity and stable yield.

[0060] The reaction equation for this invention is:

[0061]

[0062] The mass ratio of pepper rings, 50% glyoxylic acid, sulfuric acid, and methanesulfonic acid in this invention is 1:1.57-1.77:1.37-1.57:0.05-0.07. Preferably, the mass ratio of 50% glyoxylic acid, 98% industrial sulfuric acid, and 99% industrial methanesulfonic acid is 1:1.57:1.37:0.07.

[0063] To avoid excessively high reaction temperatures that could cause the 3,4-methylenedioxyphenylethanolic acid intermediate to clump, affecting quality and yield, this invention employs a pre-cooling temperature of -10 to 0°C for the mixed acid, followed by the dropwise addition of piperonyl rings. The reaction is maintained at 0 to 5°C for 2 to 4 hours, and then continued at 10 to 30°C for 17 to 19 hours. Preferably, sulfuric acid, 50% glyoxylic acid, and methanesulfonic acid are mixed, pre-cooled, and the temperature is controlled at 0°C. Piperone rings are then added dropwise, and the reaction is maintained at 0°C for 2 hours, followed by continued reaction at 20°C for 17 hours.

[0064] This invention oxidizes 3,4-methylenedioxyphenylethanolic acid to piperine using an oxidative decarboxylation system composed of sulfuric acid, silica gel chromatography, and 5% nitric acid.

[0065] The system is 3,4-methylenedioxyphenylethanolic acid: 93%–98% sulfuric acid: silica gel chromatography: 5% nitric acid, with a ratio of m:m:m:v = 1:0.1–0.3:0.1–0.3:5–8. Preferably, the ratio is 3,4-methylenedioxyphenylethanolic acid: 98% sulfuric acid: silica gel chromatography: 5% nitric acid, with a ratio of m:m:m:v = 1:0.1:0.1:5.

[0066] The present invention is used to oxidize and decarboxylate 3,4-methylenedioxyphenylethanolic acid at a controlled oxidation temperature of 75–85°C in an oxidative decarboxylation system. Preferably, the controlled temperature is 80°C.

[0067] In this invention, after the oxidative decarboxylation reaction is completed, the upper layer of dilute acid solution is first poured off, and the lower layer, containing piperine and an oily silica gel, is washed three times with hot water at 75-85°C to remove unreacted 3,4-methylenedioxyphenylethanolic acid. Preferably, the washing is done three times with hot water at 85°C.

[0068] In this invention, after washing, the sample is extracted three times with 4-6 times the volume of the reactant in ethyl acetate. The extracts are combined, and the solvent is discarded under reduced pressure to obtain piperine, a red oily substance. Preferably, it is extracted three times with 5 times the volume of ethyl acetate.

[0069] The present invention crystallizes the obtained piperine red oily substance with 5 to 8 times the amount of 50 to 75% ethanol at -10 to 0°C, filters, and dries the filter cake at room temperature. The dried product is recrystallized with 3 to 5 times the amount of 95% ethanol at -10 to 0°C, filtered, and dried at room temperature to obtain piperine with a purity >98% and a yield >90% based on 3,4-methylenedioxyphenylethanolic acid.

[0070] Preferredly, 8 times the amount of 75% ethanol is used to crystallize at -5℃, filtered, and the filter cake is dried at room temperature. The dried product is recrystallized with 5 times the amount of 95% ethanol at -5℃, filtered, and dried at room temperature to obtain piperonal.

[0071] Features of this invention:

[0072] The preparation of 3,4-methylenedioxyphenylethanolic acid using a sulfuric acid-methanesulfonic acid mixed acid catalysis has advantages such as mild reaction and non-caking of reactants. The preparation of piperine using a sulfuric acid-silica gel chromatography-nitric acid oxidation system has advantages such as fewer byproducts and easier separation of impurities. The method of this invention has advantages such as mild reaction, controllable process, fewer byproducts, easy separation and purification, stable reaction, and high overall yield, which can significantly reduce production costs and is suitable for large-scale industrial production. Attached Figure Description

[0073] Figure 1 : The reaction equation for the preparation method of the present invention.

[0074] Figure 2 : Figure 9 shows the preparation of 3,4-methylenedioxyphenylethanolic acid by the reaction of 50% glyoxylic acid, 98% industrial sulfuric acid, and methanesulfonic acid.

[0075] Figure 3 : Figure 5 shows the preparation of 3,4-methylenedioxyphenylethanolic acid by the reaction of 50% glyoxylic acid, 93% industrial sulfuric acid, and methanesulfonic acid.

[0076] Figure 4 : Comparative Example 1: Preparation of 3,4-methylenedioxyphenylethanolic acid by reaction of 50% glyoxylic acid and 98% industrial sulfuric acid.

[0077] Figure 5 Figure 19 shows the preparation of piperine by the reaction of 3,4-methylenedioxyphenylethanolic acid-98% sulfuric acid-silica gel chromatography-5% nitric acid = 1:0.1:0.1:5.

[0078] Figure 6Figure 17 shows the preparation of piperine by the reaction of 3,4-methylenedioxyphenylethanolic acid-98% sulfuric acid-silica gel chromatography-5% nitric acid = 1:0.1:0.1:8.

[0079] Figure 7 Figure: Preparation of piperine by reaction of 3,4-methylenedioxyphenylethanolic acid-5% nitric acid = 1:5 in Comparative Example 2.

[0080] Figure 8 Infrared spectrum of 3,4-methylenedioxyphenylethanolic acid, the glyoxylic acid-sulfuric acid-methanesulfonic acid catalytic product of the present invention.

[0081] Figure 9 Infrared spectrum of 3,4-methylenedioxyphenylethanolic acid, a product of single sulfuric acid catalysis.

[0082] Figure 10 Infrared spectrum of piperine, the sulfuric acid-silica gel-nitric acid oxidation product of the present invention.

[0083] Figure 11 Infrared spectrum of piperine, a single product of nitric acid oxidation.

[0084] in: Figures 2-9 The developing solvent used was petroleum ether:ethyl acetate = 4:1, and iodine was used for color development. Detailed Implementation

[0085] To facilitate the explanation of the technical solution and effects of the present invention, the present invention will be compared and explained below through embodiments and comparative embodiments.

[0086] Example 1:

[0087] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 6.1 g (0.06 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -10 to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0 to 5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 100.0 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 82%.

[0088] Example 2:

[0089] like Figure 1As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -10 to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0 to 5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 111.2 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 91%.

[0090] Example 3:

[0091] like Figure 1 As shown, 203.7 g (1.38 mol) of 50% glyoxylic acid and 7.3 g (0.08 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 175.8 g (1.79 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -10 to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0 to 5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 102.5 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 84%.

[0092] Example 4:

[0093] like Figure 1 As shown, 215.9 g (1.46 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 187.7 g (1.91 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -10 to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0 to 5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 101.2 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 83%.

[0094] Example 5:

[0095] like Figure 1As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 155.4 g (1.67 mol) of 93% industrial sulfuric acid. The flask was pre-cooled to -10 to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0 to 5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 98.8 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 81%.

[0096] Example 6:

[0097] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -10°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0–5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 103.7 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 85%.

[0098] Example 7:

[0099] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to -5°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0–5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 102.9 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 84%.

[0100] Example 8:

[0101] like Figure 1As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0–5°C for 2 hours, and then continued at room temperature for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 109.8 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 90%.

[0102] Example 9:

[0103] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0°C for 2 hours, and then continued at 20°C for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 113.5 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 93%.

[0104] Example 10:

[0105] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 5°C for 2 hours, and then continued at 10°C for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 107.1 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 88%.

[0106] Example 11:

[0107] like Figure 1As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 3°C ​​for 2 hours, and then continued at 30°C for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 103.7 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 85%.

[0108] Example 12:

[0109] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0°C for 4 hours, followed by a further reaction at 20°C for 18 hours, after which the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 106.3 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 87%.

[0110] Example 13:

[0111] like Figure 1 As shown, 191.5 g (1.29 mol) of 50% glyoxylic acid and 8.5 g (0.09 mol) of 99% methanesulfonic acid were added sequentially to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0°C for 3 hours, followed by a further reaction at 20°C for 19 hours, after which the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 106.7 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 87%.

[0112] Example 14:

[0113] like Figure 1As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 75–85 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 180.4 g of piperonal, with a yield of 92%.

[0114] Example 15:

[0115] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 39.2 g of 98% sulfuric acid, 39.2 g of silica gel for chromatography, and 1372 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 75–85 °C. The reaction was carried out for 20–25 min, and the reaction was detected by TLC. The reaction was then complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 177.7 g of piperonal, with a yield of 91%.

[0116] Example 16:

[0117] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 58.8 g of 98% sulfuric acid, 58.8 g of silica gel for chromatography, and 1176 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 75–85 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 177.0 g of piperonal, with a yield of 90%.

[0118] Example 17:

[0119] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 1568 ml of 5% nitric acid (8 times the volume) were added. The stirring was started, and the temperature was slowly raised to 75–85 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, it was recrystallized again with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 173.4 g of piperonal, with a yield of 88%.

[0120] Example 18:

[0121] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 75°C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85°C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, it was recrystallized again with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 174.0 g of piperonal, with a yield of 89%.

[0122] Example 19:

[0123] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol at -5 °C. After filtration and drying at room temperature, it was recrystallized again with 5 times the volume of 95% ethanol at -5 °C, filtered, and dried at room temperature to obtain 178.4 g of piperonal, with a yield of 91%.

[0124] Example 20:

[0125] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 85°C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85°C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized again with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 174.5 g of piperonal, with a yield of 89%.

[0126] Example 21:

[0127] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 4 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 168.2 g of piperonal, with a yield of 86%.

[0128] Example 22:

[0129] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 6 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol. After filtration and drying at room temperature, the mixture was recrystallized with 5 times the volume of 95% ethanol, filtered, and dried at room temperature to obtain 172.2 g of piperonal, with a yield of 88%.

[0130] Example 23:

[0131] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanol was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 5 times the volume of 75% ethanol at -10 °C. After filtration and drying at room temperature, it was recrystallized again with 3 times the volume of 95% ethanol at -10 °C, filtered, and dried at room temperature to obtain 170.3 g of piperonal, with a yield of 87%.

[0132] Example 24:

[0133] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water. Then, it was extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 6 times the volume of 75% ethanol at -5 °C. After filtration and drying at room temperature, it was recrystallized again with 4 times the volume of 95% ethanol at -5 °C. After filtration and drying at room temperature, 166.6 g of piperonal was obtained, with a yield of 85%.

[0134] Example 25:

[0135] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water. Then, it was extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol at 0 °C. After filtration and drying at room temperature, it was recrystallized again with 5 times the volume of 95% ethanol at 0 °C. After filtration and drying at room temperature, 174.8 g of piperonal was obtained, with a yield of 89%.

[0136] Example 26:

[0137] like Figure 1 As shown, 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. Then, 19.6 g of 98% sulfuric acid, 19.6 g of silica gel for chromatography, and 980 ml of 5% nitric acid (5 times the volume) were added. The stirring was started, and the temperature was slowly raised to 80 °C. The reaction was carried out for 20–25 min, and the reaction was monitored by TLC until it was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water, and then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 50% ethanol at -5 °C. After filtration and drying at room temperature, it was recrystallized again with 5 times the volume of 95% ethanol at -5 °C, filtered, and dried at room temperature to obtain 168.1 g of piperonal, with a yield of 86%.

[0138] Comparative Example 1:

[0139] 191.5 g (1.29 mol) of 50% glyoxylic acid was added to a 2000 ml flask containing 163.8 g (1.67 mol) of 98% industrial sulfuric acid. The flask was pre-cooled to 0°C in a freezer, then transferred to a 2000 ml plastic cup equipped with a rectangular stirrer. Stirring was started, and 122 g (1.00 mol) of piperine was slowly added dropwise. After the addition was complete, the reaction was maintained at 0°C for 2 hours, then continued at 20°C for 17 hours until the reaction was complete. The mixture was filtered, washed with 500 ml of tap water, and the filter cake was allowed to dry naturally to obtain 68.2 g of 3,4-methylenedioxyphenylethanolic acid, with a yield of 56%.

[0140] Comparative Example 2:

[0141] 196 g (1.00 mol) of 3,4-methylenedioxyphenylethanolic acid was added to a 2000 ml three-necked flask equipped with a stirrer, water bath heating, and outlet condenser. 980 ml of 5% nitric acid (5 times the volume of the flask) was added, and the mixture was stirred and slowly heated to 80 °C. The reaction was allowed to proceed for 20–25 min, and TLC was used to determine the reaction was complete. The upper aqueous layer was decanted, and the lower oily layer was washed three times with 1000 ml of 85 °C hot water. The mixture was then extracted three times with 5 times the volume of ethyl acetate. The extraction solvents were combined, and the lower aqueous layer was removed using a separatory funnel. The solvent was removed under reduced pressure, and the mixture was crystallized with 8 times the volume of 75% ethanol at -5 °C. The crystals were filtered, dried at room temperature, and recrystallized again with 5 times the volume of 95% ethanol at -5 °C. The crystals were filtered, dried at room temperature, and 143.1 g of piperonal was obtained, with a yield of 73%.

[0142] Table 1. Optimization of material ratio for preparing intermediate 3,4-methylenedioxyphenylethanolic acid.

[0143]

[0144] Table 2. Optimization of precooling temperature for the preparation of 3,4-methylenedioxyphenylethanolic acid intermediate.

[0145]

[0146]

[0147] Table 3. Optimization of reaction temperature for the preparation of 3,4-methylenedioxyphenylethanolic acid intermediate.

[0148]

[0149] Table 4. Optimization of reaction time for the preparation of 3,4-methylenedioxyphenylethanolic acid intermediate.

[0150]

[0151] Table 5. Optimization of material ratios for the preparation of piperine by oxidation of 3,4-methylenedioxyphenylethanolic acid.

[0152]

[0153]

[0154] Table 6. Optimization of reaction temperature for the preparation of piperine by oxidation of 3,4-methylenedioxyphenylethanolic acid.

[0155]

[0156] Table 7. Optimization of extraction conditions for the preparation of piperine by oxidation of 3,4-methylenedioxyphenylethanolic acid.

[0157]

[0158] Table 8. Optimization Experiment for the Preparation of Piperaldehyde Crystallization by Oxidation of 3,4-Methylenedioxyphenylethanol Acid

[0159]

[0160]

[0161] Table 9 Comparison of Experimental Implementation

[0162]

[0163] Appendix 1: Explanation of TLC Process Control Chart

[0164] The diagram of 3,4-methylenedioxyphenylethanolic acid in Example 9 is shown below. Figure 2 As shown.

[0165] The diagram of 3,4-methylenedioxyphenylethanolic acid in Example 5 is shown below. Figure 3 As shown.

[0166] The diagram of 3,4-methylenedioxyphenylethanolic acid in Comparative Example 1 is shown below. Figure 4 As shown.

[0167] Piperaldehyde prepared in Example 19 is shown in the figure. Figure 5 As shown.

[0168] Piperaldehyde prepared in Example 17 is shown in the figure. Figure 6 As shown.

[0169] The image of piperaldehyde prepared in Comparative Example 2 is shown below. Figure 7 As shown.

[0170] Appendix 2: Explanation of the Infrared Spectrum of 3,4-Methylenedioxyphenylethanol Acid

[0171] The infrared spectrum of 3,4-methylenedioxyphenylethanolic acid, the glyoxylic acid-sulfuric acid-methanesulfonic acid catalytic product of this invention, is shown below. Figure 8 As shown.

[0172] The infrared spectrum of 3,4-methylenedioxyphenylethanolic acid, the product of single sulfuric acid catalysis, is shown below. Figure 9 As shown.

[0173] Figure 8 and Figure 9 These are the infrared spectra of 3,4-methylenedioxyphenylethanolic acid prepared under two different catalytic conditions. Both spectra are located at 3451, 3417, 2907, 1715, 1486, 1445, 1248, 1202, 1068, 1043, 936, and 812 cm⁻¹. -1 The presence of strong absorption peaks at certain positions, along with the high consistency in peak position, intensity, and shape, indicates that the main product is 3,4-methylenedioxyphenylethanolic acid. However, careful comparison of the two images reveals some differences in peak position, intensity, and shape. Specifically, the absorption peaks at 3451, 2907, 1715, and 1043 have a 2cm difference in position. -1 Left and right displacement. For example... Figure 9 As shown, the absorption intensity of the single sulfuric acid catalyst product is relatively strong in the wavenumber range of 4000-2500. The strongest absorption peak of the single sulfuric acid catalyst product is at 3453 cm⁻¹. -1 The absorption strength reaches 35% (T); such as Figure 8 As shown, the strongest absorption peak of the sulfuric acid-methanesulfonic acid catalytic product of the present invention is 3451 cm⁻¹. -1 The absorption intensity was only 43% (T), which is relatively weak. The differences in the above infrared spectral absorption characteristics indicate that the process of preparing 3,4-methylenedioxyphenylethanolic acid using sulfuric acid-methanesulfonic acid catalysis is superior.

[0174] Appendix 3: Explanation of the Infrared Spectrum of Piperanol

[0175] The infrared spectrum of piperine, the sulfuric acid-silica gel-nitric acid oxidation product of this invention, is shown below. Figure 10 As shown.

[0176] The infrared spectrum of piperine, a single nitric acid oxidation product, is shown below. Figure 11 As shown.

[0177] like Figure 10 and Figure 11 These are the infrared spectra of piperine prepared under two different oxidation conditions. Both spectra are located at 2999, 2919, 2794, 1670, 1599, 1490, 1446, 1251, 1095, 1033, 927, 812, and 784 cm⁻¹. -1 The presence of strong absorption peaks at certain positions, along with the high consistency in peak position, intensity, and shape, indicates that the main product is piperonal. However, careful comparison of the two images reveals some differences in peak position, intensity, and shape. The most significant difference is as follows: Figure 10 As shown, the strongest absorption peak of the product obtained by sulfuric acid-silica gel-nitric acid oxidation in this invention is 1670 cm⁻¹. -1 ;like Figure 11 As shown, the strongest peak of the product obtained from nitric acid oxidation is at 1250 cm⁻¹. -1 Meanwhile, the former is at 3000cm -1 The absorption peak clusters nearby are significantly stronger than those behind. Furthermore, the absorption peaks at 2999, 2919, 1670, 1490, 1251, 1095, 1033, and 927 cm⁻¹ are also significantly stronger. -1 Some characteristic peaks are located at positions 2cm apart. -1 The left-right displacement. The differences in the above infrared spectral absorption characteristics indicate that the nitric acid-sulfuric acid-chromatographic silica gel oxidation process used in this invention to prepare piperine is superior.

Claims

1. A method for preparing piperine, characterized in that, The method includes the following steps: Step 1: Mix 50% glyoxylic acid, 98% sulfuric acid, and 99% methanesulfonic acid in the specified proportions and pre-cool to -10~0℃. Step 2: Add pepper rings dropwise, controlling the reaction temperature at 0~5℃ during the process; after the addition is complete, react for 2~4 hours, then transfer to 10~30℃ and react for another 17~19 hours. The mass ratio of the pepper rings: 50% glyoxylic acid: 98% sulfuric acid: 99% methanesulfonic acid is 1:1.57~1.77:1.37~1.57:0.05~0.07; Step 3: Wash with tap water 3-5 times to neutralize pH, then air dry to obtain 3,4-methylenedioxyphenylglycolic acid intermediate; Step 4: The intermediate 3,4-methylenedioxyphenylethanolic acid was oxidized and decarboxylated using a 98% sulfuric acid-silica gel chromatography-5% nitric acid oxidation system. After extraction with ethyl acetate, concentration, ethanol crystallization, and recrystallization, piperonal was obtained. The mass ratio of the materials in the mixture of 3,4-methylenedioxyphenylethanolic acid, 98% sulfuric acid, silica gel, and 5% nitric acid is 1:0.1~0.3:0.1~0.3:5~8. In step 4: The temperature for preventing bumping during the oxidative decarboxylation process is 75~85℃; In step 4: After the reaction is complete, first pour off the upper layer of dilute acid solution, and then wash the lower layer of piperine and silica gel mixture three times with hot water at 75~85℃. In step 4: Based on 3,4-methylenedioxyphenylethanolic acid, the washed mixed oily substance was extracted three times with 4 to 6 times the amount of ethyl acetate to obtain an ethyl acetate extract containing piperonal. The ethyl acetate extract was concentrated under reduced pressure to remove the solvent, yielding a red oily substance. This substance was dissolved in 5-8 times the amount of 50-75% ethanol and crystallized once at -10 to 0°C. The crude product was then dissolved again in 3-5 times the amount of 95% ethanol and recrystallized once at -10 to 0°C to obtain piperine.

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