Process for chloromethylation and process for the preparation of piperonyl butoxide

Abstract

The application belongs to the technical field of organic synthesis, and discloses a chloromethylation method and a preparation method of piperonyl butoxide. The chloromethylation method comprises the following steps: using a chlorine salt and concentrated sulfuric acid as precursors of a chloromethylation reagent, and performing a chloromethylation reaction on dihydrocuminaldehyde and trioxane. The chloromethylation method can ensure that a large amount of waste acid and new impurities are not introduced in the preparation process of piperonyl butoxide, and gas hydrogen chloride is not used, so that the safety is improved, and the obtained piperonyl butoxide is high-purity, for example, the purity is not less than 99.5%.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a chloromethylation method and a method for preparing piperonyl butyl ether. Background Technology

[0002] Piperyl butyl ether has a wide range of applications. Besides being used as an insecticide synergist, it also plays a crucial role in detection and drug development. In particular, high-purity piperin butyl ether can be used as a standard or reference material to calibrate testing instruments and verify experimental methods, ensuring the accuracy of pesticide residue analysis and detection, making it a key link in the quality control process. Therefore, obtaining high-purity piperin butyl ether is an urgent need in the industry.

[0003] There are many existing methods for preparing piperine butyl ether, but most of these methods have drawbacks (e.g., generating large amounts of waste acid, resulting in poor environmental performance), or the piperine butyl ether obtained has a high impurity content, or the types of impurities are uncertain, which limits the application of piperine butyl ether products.

[0004] Existing invention patent 1 (CN 1752083A) is entitled "Production Process of Piperyl Butyl Ether Synthesized from Safrole Oil". Existing invention patent 2 (CN 106699721A) is also entitled "Production Process of Piperyl Butyl Ether Synthesized from Safrole Oil". Existing invention patent 1 uses safrole oil as the initial raw material and prepares the piperin-butyl ether product through a series of hydrogenation, chloromethylation, and etherification reactions. In the hydrogenation process, lithium-nickel alloy powder is used as a catalyst, and safrole oil reacts with hydrogen to obtain dihydrosafrole. In the chloromethylation process, dihydrosafrole, hydrochloric acid, paraformaldehyde, and the auxiliary agent tetraethylammonium bromide react to obtain chloromethyldihydrosafrole. In the etherification process, chloromethyldihydrosafrole reacts with sodium hydroxide, monobutyl ether, and diethylamine to obtain piperin-butyl ether. Existing invention patent 2 has a similar technical solution to existing invention patent 1.

[0005] Both existing invention patents 1 and 2 use large amounts of concentrated hydrochloric acid as the chloromethylation reagent in their chloromethylation reactions, generating a large amount of waste acid after the reaction, which is extremely environmentally unfriendly. The piperonyl butyl ether produced by existing invention patents 1 and 2 has a purity of 95%–98%, which is low, and the control indicators for impurities are not clearly stated, posing a risk of product obsolescence. Furthermore, both the chloromethylation and etherification processes use auxiliaries, introducing new impurities and making product purification and impurity control more difficult.

[0006] Existing invention patent 3 (CN 121226309 A), entitled "Piperidine Butyl Ether and its Preparation Method," builds upon existing invention patent 1. In the chloromethylation process, it uses dihydrosafrole, acetyl chloride, a small amount of concentrated hydrochloric acid, and paraformaldehyde, significantly reducing the use of concentrated hydrochloric acid and wastewater generation. Furthermore, it eliminates the use of auxiliaries in both the chloromethylation and etherification processes, resulting in a piperidine butyl ether product with a purity exceeding 98%. However, the control of impurities is not clearly defined.

[0007] Existing invention patent 4 (CN120965449A) is entitled "A Method for Preparing 2,5-Disubstituted Benzyl Chloride." In this method, chloromethyl liquid and disubstituted benzene undergo a chloromethylation reaction in hydrogen chloride gas. The concentration of hydrogen chloride is increased by adding hydrogen chloride gas, thereby accelerating the chloromethylation reaction. While this method uses hydrogen chloride gas as the chloromethylation reagent to increase the reaction rate, it poses significant safety risks during the transportation and use of hydrogen chloride gas. Therefore, this technology carries obvious safety risks.

[0008] Prior art invention patent 5 (CN 1255399C) is entitled "Purification Method of Piperyl Butyl Ether Synthesized from Safrole Oil". Prior art invention patent 6 (CN 120322276 A) is entitled "Distillation Method Including Rectification for Obtaining High Purity Piperyl Butyl Ether (PBO)".

[0009] The aforementioned prior art invention patent 5 employs a molecular distillation apparatus, performing two-stage separation by adjusting parameters such as pressure, evaporation temperature, cooling temperature, temperature difference between the evaporator and condenser, and stirring rate to obtain piperine butyl ether with a purity of over 98%. However, this technology only studies the separation and purification of piperine butyl ether, without addressing the control of impurity content.

[0010] The aforementioned prior art invention patent 6 employs a multi-stage continuous distillation method to separate and purify piperine butyl ether. By adjusting process parameters such as the theoretical number of stages, reflux ratio, and vacuum degree, it achieves the purification of high-content piperine butyl ether and describes the control of some impurities (DPM and DPE). However, this technology also has problems: First, it only studies the separation and purification steps of the final product and does not address the process of impurity generation, thus failing to fundamentally solve the problem of impurity control; second, it only describes the control of some impurities and does not address the most important impurity, dihydrosafrole (DHS).

[0011] In addition, some existing technologies have been used to study the formation reaction of chloromethyldihydrosafrole (involving chloromethylation reaction). For example, (1) in 1949, Wachs H. et al. reacted 40% formaldehyde aqueous solution, concentrated hydrochloric acid and dihydrosafrole as raw materials for 36 hours to obtain chloromethyldihydrosafrole with a yield of 60%. (2) in 1959, Wachs H. et al. changed to paraformaldehyde and concentrated hydrochloric acid as raw materials, which increased the yield to more than 98% and the purity to about 95%. In the same year, they made another improvement to the chloromethylation method in US Patent US2485680 by adding anhydrous calcium chloride to concentrated hydrochloric acid, and the reaction yield also reached more than 95%. (3) in 1961, Shirt S. reacted paraformaldehyde, concentrated hydrochloric acid and dihydrosafrole together and added glacial acetic acid to obtain chloromethyldihydrosafrole with a yield of 77%. (4) In 1965, Lurik BB et al. used paraformaldehyde and 34% hydrochloric acid as chloromethylating agents, with a reaction temperature of 90℃ and a yield of 74.5%. (5) In 1972, Robert J. H. et al. added zinc chloride as a catalyst to the chloromethylating agents paraformaldehyde and concentrated hydrochloric acid, achieving a yield of 89.9%. (6) In 1982, Otto R. et al. reacted paraformaldehyde and piperonyl propane with 20% hydrochloric acid, achieving a yield of 88.2%. (7) In 1997, Shen Dongsheng et al. prepared chloromethyldihydrosafrole by reacting dihydrosafrole with 37% formaldehyde solution, 36% hydrochloric acid, and a phase transfer catalyst tetraethylammonium bromide, achieving a yield as high as 96.6% and a localization selectivity of 100%. (8) In 2000, Tang Daoqiong et al. used a self-made compound A-phase transfer catalyst and paraformaldehyde and 30% hydrochloric acid as raw materials to prepare chloromethyl dihydrosafrole with a yield of 97.7%. (9) In 2001, Lan Wenxiang et al. stirred dihydrosafrole with paraformaldehyde and 36% concentrated hydrochloric acid at 70°C for 7 hours to obtain a product yield of 98.6%. (10) In 2011, Wang Shuai et al. reacted dihydrosafrole with paraformaldehyde and 38% concentrated hydrochloric acid in the presence of cyclohexane at 70°C for 6 hours, continuously adding phosphorus trichloride during the reaction, and the total yield of the two steps reached 91.8%.

[0012] Based on the aforementioned existing technology and the chloromethylation reaction mechanism, it is known that the main influencing factor in the chloromethylation reaction is controlling the concentration of hydrogen and chloride ions in the system, which directly affect the rate and selectivity of the chloromethylation reaction. This mechanism is also described in US Patent US2846480A. Through the research on side reactions during the chloromethylation process by Wang Shuai et al., it can be found that of the three main impurities of piperonyl butyl ether (DHS, DPM, and DPE), except for DHS which is a reactant, the other two impurities (DPM and DPE) are generated during the chloromethylation process.

[0013] The mechanism lies in: when chloride ions (Cl) in the system - When the chloride ion concentration is insufficient, the intermediates generated in the chloromethylation reaction (such as chloromethyl dihydrosafrole) will undergo Friedel-Crafts alkylation with the unreacted starting material (dihydrosafrole) to generate bispiperylmethane (DPM); or the intermediates may undergo etherification to generate bispiperyl ether (DPE). Therefore, increasing the chloride ion concentration is a key factor in inhibiting the formation of DPM and DPE and improving the reaction selectivity.

[0014] However, existing methods for increasing chloride ion concentration all have significant drawbacks: Method 1 (Prior Patent 1, Prior Patent 2, and most related literature): uses a large amount of concentrated hydrochloric acid (30%-38% by mass). While this method can provide a high concentration of chloride ions, it introduces a large amount of water, resulting in a huge amount of waste acid (approximately 350%-500% of the mass of dihydrosafrole), which is extremely environmentally unfriendly. Method 2 (Prior Patent 4 and US2846480A): uses hydrogen chloride gas. This method can provide anhydrous or low-water high-concentration hydrogen chloride, but hydrogen chloride gas poses significant safety risks and operational difficulties during storage, transportation, and use. Method 3 (Invention Patent CN121226309A): uses acetyl chloride and a small amount of concentrated hydrochloric acid. This method significantly reduces waste acid, but the reaction of acetyl chloride generates acetic acid as a byproduct, introducing new organic impurities (acetic acid and its derivatives), increasing the purification burden, and failing to fundamentally solve the problem of precise control of chloride ion concentration.

[0015] Therefore, there is an urgent need for a method for preparing piperyl butyl ether that can provide a high concentration of chloride ions to suppress side reactions and control DPM and DPE impurities at the source, while avoiding the generation of large amounts of waste acid and the introduction of new organic impurities, and is safe and environmentally friendly. Summary of the Invention

[0016] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention proposes a chloromethylation method and a method for preparing piperonyl butyl ether. The chloromethylation method of the present invention ensures that the preparation process of piperonyl butyl ether does not introduce large amounts of waste acid and new impurities, and does not use gaseous hydrogen chloride, thus improving safety. Moreover, the obtained piperonyl butyl ether is of high purity, for example, with a purity of not less than 99.5%.

[0017] This invention provides a method for preparing piperyl butyl ether that can provide a high concentration of chloride ions to suppress side reactions and control DPM and DPE impurities at the source, while avoiding the generation of large amounts of waste acid and the introduction of new organic impurities, and is safe and environmentally friendly.

[0018] A first aspect of the present invention provides a method for chloromethylation.

[0019] Specifically, a chloromethylation method includes the following steps: Chloride salts and concentrated sulfuric acid were used as precursors for chloromethylation, and chloromethylation was carried out with dihydrosafrole and trioxymethylene.

[0020] Preferably, the chloride salt includes an alkali metal chloride salt or an alkaline earth metal chloride salt; more preferably, sodium chloride or potassium chloride.

[0021] Preferably, the concentrated sulfuric acid has a mass fraction greater than 70%.

[0022] Preferably, the concentrated sulfuric acid has a mass of 25%-45% of that of safrole dihydro; more preferably, it has a mass of 33%-45%.

[0023] Preferably, the mass of the chloride salt is 35%-54% of the mass of safrole dihydro; more preferably, it is 39%-54%.

[0024] Preferably, the mass of the trioxymethylene is 15%-30% of the mass of safrole; more preferably, it is 22%-27.5%.

[0025] Preferably, the chloromethylation method includes the following steps: Dihydrosafrole was mixed with chloride salt and trioxymethylene, the temperature was increased, and concentrated sulfuric acid was added dropwise to carry out a chloromethylation reaction.

[0026] Preferably, the temperature of the chloromethylation reaction is 10-50°C; more preferably, it is 45-50°C.

[0027] Preferably, the chloromethylation reaction takes 5-10 hours. Of these 5-10 hours, 4-7 hours are for the addition of concentrated sulfuric acid.

[0028] Preferably, after the chloromethylation reaction is completed, separation is performed to obtain crude chloromethyldihydrosafrole.

[0029] Preferably, the separation includes filtration or sedimentation, and phase separation. Filtration or sedimentation removes sulfates produced in the reaction, such as sodium sulfate. Phase separation removes unreacted concentrated sulfuric acid.

[0030] Preferably, the dihydrosafrole is generated by mixing and reacting safrole oil with hydrogen under the action of a catalyst.

[0031] Preferably, the catalyst is selected from at least one of lithium-nickel alloy powder, palladium on carbon, and Raney nickel.

[0032] Preferably, the mass of the catalyst is 0.1%-10% of the mass of the sassafras oil; more preferably, it is 1%-10%.

[0033] Preferably, the mass of the hydrogen is 0.5%-3% of the mass of the sassafras oil; more preferably, it is 1%-2.5%.

[0034] Preferably, the mixing reaction is carried out at a reaction temperature of 50-150°C, a reaction pressure of 0.5-1.5 MPa, and a reaction time of 180-300 minutes.

[0035] A second aspect of the present invention provides a method for preparing piperonyl butyl ether.

[0036] Specifically, a method for preparing piperonyl butyl ether includes the following steps: The preparation method includes the above-mentioned chloromethylation method to obtain crude chloromethyldihydrosafrole, which is then etherified to obtain the piperonyl butyl ether.

[0037] Preferably, the etherification process involves mixing and reacting the crude chloromethyldihydrosafrole with an alkaline solution and diethylene glycol monobutyl ether to obtain piperonyl butyl ether.

[0038] Preferably, the alkaline solution comprises a sodium hydroxide solution or a potassium hydroxide solution; more preferably, a sodium hydroxide solution.

[0039] Preferably, the alkaline solution has a mass fraction greater than 48%. For example, a sodium hydroxide solution with a mass fraction greater than 48%.

[0040] Preferably, the mass of the alkaline solution is 35%-65% of the crude chloromethyldihydrosafrole mass; more preferably, it is 43%-62%.

[0041] Preferably, the mass of the diethylene glycol monobutyl ether is 45%-85% of the crude mass of chloromethyldihydrosafrole; more preferably, it is 55%-80%.

[0042] Preferably, the reaction temperature is 80-150°C and the reaction time is 8-12 hours.

[0043] A piperyl butyl ether is prepared by the above preparation method, and the purity of the piperyl butyl ether, calculated by mass fraction, is greater than or equal to 99.5%, and the content of the impurity dihydrosafrole (DHS) is <40ppm.

[0044] Preferably, the piperyl butyl ether further contains impurities dipiperylmethane (DPM) and dipiperyl ether (DPE), and the content of dipiperylmethane (DPM) is <0.1% and the content of dipiperyl ether (DPE) is <0.1% by mass fraction.

[0045] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) In the chloromethylation method of the present invention, concentrated sulfuric acid is not used as a catalyst and dehydrating agent, but as a precursor of the chloromethylation reagent to react with dihydrosafrole and trioxymethylene in the chloromethylation reaction. This avoids the safety problems caused by the use of hydrogen chloride gas, and also helps to reduce the generation of impurities, which is beneficial to the production of high-purity piperonyl butyl ether.

[0046] (2) This invention abandons the traditional method of directly using concentrated hydrochloric acid or hydrogen chloride gas, and instead uses concentrated sulfuric acid and sodium chloride to react in situ in the reaction system to generate hydrogen chloride. This design achieves the following objectives: a. Solve the problem of using large amounts of concentrated hydrochloric acid and generating large amounts of waste acid during the chloromethylation process.

[0047] b. Address the safety concerns associated with the direct use of hydrogen chloride gas.

[0048] c. Solve the quality problem of piperidine butyl ether product from the source: Provide high concentration of chloride ions in an anhydrous / low water environment through in-situ reaction to promote the complete chloromethylation reaction and suppress side reactions (especially the formation of DPM and DPE) to the greatest extent, thereby achieving effective control of the main impurities DHS, DPM and DPE. Attached Figure Description

[0049] Figure 1 The GC (gas chromatography) spectrum of piperonyl butyl ether prepared in Example 1 of this invention; Figure 2 The GC spectrum of piperoyl butyl ether prepared according to the process route of prior art invention patent 1 (CN 1752083A). Detailed Implementation

[0050] To enable those skilled in the art to more clearly understand the technical solutions described in this invention, the following embodiments are provided for illustration. It should be noted that the following embodiments do not constitute a limitation on the scope of protection claimed by this invention.

[0051] Unless otherwise specified, the raw materials, reagents or devices used in the following examples are available from conventional commercial sources or can be obtained by existing known methods.

[0052] The concentrated sulfuric acid used in the following examples has a mass fraction of 98%.

[0053] The mass fraction of concentrated hydrochloric acid used in the following comparative examples is 36%.

[0054] Example 1 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 300 kg of paraformaldehyde and 565 kg of sodium chloride. The reaction temperature was 45 °C. 475 kg of concentrated sulfuric acid was added dropwise over 6 hours. After the addition was complete, the reaction continued for another 2 hours. After the reaction was completed, the sodium sulfate was removed by filtration. Then, the unreacted concentrated sulfuric acid was separated. The remaining material was crude chloromethyl safrole, with a mass of 1500 kg and a purity of 94.5% (mass fraction).

[0055] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 24Kg of Raney nickel catalyst were added. Under the process conditions of 90℃ and reactor pressure of 1MPa, 20Kg of hydrogen gas was continuously introduced and the reaction was carried out for 250 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0056] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1500 kg of crude chloromethyldihydrosafrole, 930 kg of sodium hydroxide solution (48% by mass), and 1200 kg of diethylene glycol monobutyl ether were added sequentially. The reaction was carried out at 90℃ for 12 hours until the reaction endpoint. The final reaction solution contained piperonyl butyl ether, which was extracted by distillation under a vacuum of below 200 Pa and a reactor temperature of 230℃. The product was analyzed using CIPAC 33 / LN / (M) method. The piperonyl butyl ether content in the final product was 99.52% (by mass), with a yield of 89.22%. Where W1 is the weight of safrole oil, C1 is the content of safrole oil, and 162.18 is the molar mass of safrole oil; where W2 is the weight of piperine butyl ether, C2 is the content of piperine butyl ether, and 338.44 is the molar mass of safrole oil.

[0057] Example 2 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 245 kg of paraformaldehyde and 470 kg of sodium chloride. The reaction temperature was 35 °C. 395 kg of concentrated sulfuric acid was added dropwise over 4 hours. After the addition was complete, the reaction continued for another 2 hours. After the reaction was completed, the sodium sulfate was removed by filtration. Then, the unreacted concentrated sulfuric acid was separated by phase separation. The remaining material was crude chloromethyl safrole, with a mass of 1500 kg and a purity of 94.0% (mass fraction).

[0058] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 12Kg of Raney nickel catalyst were added. Under the process conditions of 120℃ and reactor pressure of 1.5MPa, 18Kg of hydrogen gas was continuously introduced and the reaction was carried out for 300 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0059] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1500Kg of crude chloromethyldihydrosafrole, 750Kg of sodium hydroxide solution (>48%), and 1050Kg of diethylene glycol monobutyl ether were added sequentially. The reaction was carried out at 150℃ for 11 hours until the reaction endpoint. The final reaction solution contained piperine butyl ether, which was extracted by distillation under a vacuum of less than 200Pa and a reactor temperature of 230℃. The product was analyzed by CIPAC 33 / LN / (M) method. The piperine butyl ether content in the final distillation product was 99.50% (mass fraction), and the yield was 87.47%.

[0060] Example 3 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 330 kg of paraformaldehyde and 640 kg of sodium chloride. The reaction temperature was 50 °C. 540 kg of concentrated sulfuric acid was added dropwise over 7 hours. After the addition was complete, the reaction continued for 1 hour. After the reaction was completed, the sodium sulfate was removed by filtration. Then, the unreacted concentrated sulfuric acid was separated. The remaining material was crude chloromethyl safrole, with a mass of 1500 kg and a purity of 94.3% (mass fraction).

[0061] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 12Kg of Raney nickel catalyst were added. Under the process conditions of 150℃ and reactor pressure of 1.5MPa, 18Kg of hydrogen gas was continuously introduced and the reaction was carried out for 300 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0062] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1500Kg of crude chloromethyldihydrosafrole, 750Kg of sodium hydroxide solution (>48%), and 1050Kg of diethylene glycol monobutyl ether were added sequentially. The reaction was carried out at 150℃ for 11 hours until the reaction endpoint. The final reaction solution contained piperine butyl ether, which was extracted by distillation under a vacuum of less than 200Pa and a reactor temperature of 230℃. The product was analyzed by CIPAC 33 / LN / (M) method. The piperine butyl ether content in the final distillation product was 99.51% (mass fraction), and the yield was 88.93%.

[0063] Comparative Example 1 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 300 kg of paraformaldehyde and 565 kg of sodium chloride. The reaction temperature was 45 °C. 475 kg of concentrated hydrochloric acid was added dropwise over 6 hours. After the addition was complete, the reaction continued for another 2 hours. After the reaction was completed, the unreacted acid was separated, and the remaining material was crude chloromethyl safrole with a mass of 1255 kg and a purity of 14.2% (mass fraction).

[0064] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 24Kg of Raney nickel catalyst were added. Under the process conditions of 90℃ and reactor pressure of 1MPa, 20Kg of hydrogen gas was continuously introduced and the reaction was carried out for 250 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0065] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1255 kg of crude chloromethyldihydrosafrole, 930 kg of sodium hydroxide solution (>48%), and 1200 kg of diethylene glycol monobutyl ether were added sequentially. The reaction was carried out at 90℃ for 12 hours until the reaction endpoint. The final reaction solution contained piperine butyl ether, which was extracted by distillation under a vacuum of less than 200 Pa and a reactor temperature of 230℃. The product was analyzed by CIPAC33 / LN / (M) method. The piperine butyl ether content in the final distillation product was 95.63% (mass fraction), and the yield was 17.20%.

[0066] The difference between Comparative Example 1 and Example 1 is that concentrated hydrochloric acid of equal mass is used instead of concentrated sulfuric acid in Example 1, while other raw materials are the same as in Example 1.

[0067] Comparative Example 2 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 300 kg of paraformaldehyde and 565 kg of sodium chloride. The reaction temperature was 45 °C, and hydrogen chloride gas was continuously introduced at a flow rate of 43.5 kg / h for 8 hours. After the reaction, the unreacted acid was separated, and the remaining material was crude chloromethyl safrole with a mass of 1522 kg and a purity of 94.8% (mass fraction).

[0068] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 24Kg of Raney nickel catalyst were added. Under the process conditions of 90℃ and reactor pressure of 1MPa, 20Kg of hydrogen gas was continuously introduced and the reaction was carried out for 250 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0069] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1522 kg of crude chloromethyldihydrosafrole, 930 kg of sodium hydroxide solution (>48%), and 1200 kg of diethylene glycol monobutyl ether were added sequentially. The reaction was carried out at 90℃ for 12 hours until the reaction endpoint. The final reaction solution contained piperine butyl ether, which was extracted by distillation under a vacuum of less than 200 Pa and a reactor temperature of 230℃. The product was analyzed by CIPAC33 / LN / (M) method. The piperine butyl ether content in the final distillation product was 99.55% (mass fraction), and the yield was 90.60%.

[0070] The difference between Comparative Example 2 and Example 1 is that hydrogen chloride gas is used instead of concentrated sulfuric acid in Example 1, while the other raw materials are the same as in Example 1.

[0071] Comparative Example 3 A chloromethylation method includes the following steps: 1200 kg of safrole was added to a 3000 L chloromethylation reactor, followed by 300 kg of paraformaldehyde and 565 kg of sodium chloride. The reaction temperature was 45 °C. 475 kg of concentrated sulfuric acid was added dropwise over 6 hours. After the addition was complete, the reaction continued for another 2 hours. After the reaction was completed, the sodium sulfate was removed by filtration. Then, the unreacted concentrated sulfuric acid was separated. The remaining material was crude chloromethyl safrole, with a mass of 1500 kg and a purity of 94.5% (mass fraction).

[0072] The preparation process of the above-mentioned dihydrosafrole is as follows: In a 2000L hydrogenation reactor, 1200Kg of safrole oil (content ≥99% by mass) and 24Kg of Raney nickel catalyst were added. Under the process conditions of 90℃ and reactor pressure of 1MPa, 20Kg of hydrogen gas was continuously introduced and the reaction was carried out for 250 minutes to obtain 1200Kg of dihydrosafrole with a content ≥99% (by mass).

[0073] A method for preparing piperonyl butyl ether includes the following steps: In a 3000L etherification reactor, 1500 kg of crude chloromethyl dihydrosafrole, 930 kg of sodium hydroxide solution (>48%), 1200 kg of diethylene glycol monobutyl ether, and 35 kg of diethylamine were added sequentially. The reaction was carried out at 90℃ for 12 hours until the reaction endpoint. The final reaction solution contained piperine butyl ether, which was extracted by distillation under a vacuum of less than 200 Pa and a reactor temperature of 230℃. The product was analyzed by CIPAC 33 / LN / (M) method. The piperine butyl ether content in the final distillation product was 98.88% (mass fraction), and the yield was 88.90%.

[0074] Product effectiveness test Piperidine prepared in Example 1 and piperine butyl ether prepared according to the process route of prior art invention patent 1 (CN 1752083A) (process parameters within the scope are taken as intermediate values), were analyzed by CIPAC 33 / LN / (M) analytical method. Figure 1 (In the diagram, "Unit" indicates a unit) and Figure 2 The GC spectrum shown is from Figure 1 and Figure 2 The following information can be obtained.

[0075] Table 1

[0076] Comparative analysis revealed that the piperyl butyl ether prepared by this invention has a content >99.5%, while ensuring that the main impurity dihydrosafrole (DHS) is <40ppm, and the contents of dipiperyl ether (DPE) and dipiperylmethane (DPM) are both less than 0.1%.

[0077] The present invention has significant effects, as detailed below: (1) In the chloromethylation process, the present invention uses hydrogen chloride gas generated by the reaction of concentrated sulfuric acid and sodium chloride to participate in the chloromethylation reaction. Compared with concentrated hydrochloric acid, it reduces the introduction of water, increases the concentration of hydrogen ions and chloride ions, and improves the selectivity of the chloromethylation reaction process. Compared with the prior art invention patent 5 and prior art invention patent 6, the present invention significantly reduces the generation of impurities DPM and DPE from the source, rather than relying solely on the final separation and purification steps for control.

[0078] (2) By using concentrated sulfuric acid and sodium chloride, the problem of using large amounts of hydrochloric acid is solved. In existing invention patents 1 and 2, when the weight ratio of dihydrosafrole is 700 parts, the weight ratio of hydrochloric acid is 2500-3500 parts, and the amount of waste acid generated is about 350%-500% of the weight of dihydrosafrole. In contrast, in this invention patent, the weight ratio of concentrated sulfuric acid is 33%-45% of the weight of dihydrosafrole, and about 20% of concentrated sulfuric acid is consumed during the reaction, generating about 10%-50% of the weight of dihydrosafrole, which greatly reduces the generation of waste acid. It is also more environmentally friendly.

[0079] (3) By adding concentrated sulfuric acid into the system and reacting it with sodium chloride to generate hydrogen chloride gas, hydrogen chloride is generated and consumed by chloromethyl reaction. Compared with the existing invention patent 4, this eliminates the safety problem of directly using hydrogen chloride gas.

[0080] (4) In this invention, hydrogen chloride produced by the reaction of concentrated sulfuric acid and sodium chloride is used as a chloromethylation reagent. By adjusting the process parameters in the chloromethylation process, the complete conversion of the raw material dihydrosafrole can be achieved. After separation by distillation, the content of dihydrosafrole (DHS) in the product can be controlled below 40 ppm. The control of this impurity is not mentioned in the existing invention patents.

[0081] (5) Compared with the prior art invention patent 1 and prior art invention patent 2, the present invention does not use any auxiliary agents in the chloromethylation and etherification reaction process, and does not introduce any new impurities, which is more conducive to the control of product quality.

Claims

1. A method for chloromethylation, characterized in that, Includes the following steps: Chloride salts and concentrated sulfuric acid were used as precursors for chloromethylation, and chloromethylation was carried out with dihydrosafrole and trioxymethylene.

2. The chloromethylation method according to claim 1, characterized in that, The chloride salt includes alkali metal chloride salts or alkaline earth metal chloride salts; and / or, the concentrated sulfuric acid has a mass fraction greater than 70%.

3. The chloromethylation method according to claim 1, characterized in that, The concentrated sulfuric acid is 25%-45% of the mass of safrole; and / or, the chloride salt is 35%-54% of the mass of safrole; and / or, the trioxymethylene is 15%-30% of the mass of safrole; more preferably 22%-27.5%.

4. The chloromethylation method according to claim 1, characterized in that, The chloromethylation method includes the following steps: Dihydrosafrole was mixed with chloride salt and trioxymethylene, the temperature was increased, and concentrated sulfuric acid was added dropwise to carry out a chloromethylation reaction.

5. The chloromethylation method according to claim 4, characterized in that, The chloromethylation reaction is carried out at a temperature of 10-50°C; and / or the chloromethylation reaction is carried out for 5-10 hours; and / or the dihydrosafrole is generated by mixing and reacting safrole oil with hydrogen under the action of a catalyst.

6. A method for preparing piperonyl butyl ether, characterized in that, Includes the following steps: The preparation method includes the chloromethylation method according to any one of claims 1-5 to obtain crude chloromethyldihydrosafrole, which is then etherified to obtain the piperonyl butyl ether.

7. The preparation method according to claim 6, characterized in that, The etherification process involves mixing the crude chloromethyldihydrosafrole with an alkaline solution and diethylene glycol monobutyl ether to obtain the piperonyl butyl ether.

8. The preparation method according to claim 7, characterized in that, The alkaline solution includes a sodium hydroxide solution or a potassium hydroxide solution; and / or, the mass of the alkaline solution is 35%-65% of the crude mass of chloromethyldihydrosafrole.

9. The preparation method according to claim 7, characterized in that, The mass of the diethylene glycol monobutyl ether is 45%-85% of the crude mass of chloromethyldihydrosafrole; and / or, the reaction temperature is 80-150℃ and the reaction time is 8-12 hours.

10. A piperyl butyl ether, characterized in that, The preparation method described in any one of claims 6-9 is used to prepare the piperoyl butyl ether, and the purity of the piperoyl butyl ether, calculated by mass fraction, is greater than or equal to 99.5%, and the content of the impurity dihydrosafrole is <40ppm.

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