Method for preparing 3,4-methylenedioxypropiophenone

Abstract

The present invention relates to a process for the preparation of 1-(1,3-benzodioxol-5-yl)-1-propanone, comprising the step of reacting 3,4-dimethylenedioxybenzene with propionic anhydride in the presence of a bulk or supported catalyst, the catalyst being selected from the group of sulfonated crosslinked divinylbenzene resins, sulfonated crosslinked divinylbenzene resins partially exchanged with iron, zinc or gallium, perfluorinated sulfone resins and perfluorinated sulfone resins partially exchanged with iron, zinc or gallium, the catalyst having an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm, as measured by DLS (Dynamic Light Scattering) or by a granulometer. The process is advantageously carried out in a continuous manner, with stoichiometric ratios between the reagents.

Description

Technical Field

[0001] The present invention relates to a novel and inventive method for preparing 3,4-methylenedioxypropiophenone, also known as 1-(1,3-benzodioxol-5-yl)-1-propanone, as represented below.

Chemical Formula

[0002] Such a method is an improved commercially feasible method that functions using a heterogeneous catalyst under solvent-free conditions.

Background Art

[0003] Alkylenedioxybenzene derivatives are very important in the fields of medicine, pesticides, biocides, performers, and food due to their applications as final products or intermediates of desired final products.

[0004] For example, compounds having insecticidal activity containing a benzo[1,3]dioxole group are described in numerous publications. Safrole and isosafrole are used in performary, and specifically, isosafrole is used in the synthesis of piperonal (benzo[1,3]dioxole-5-carboxaldehyde) used for manufacturing fragrances and flavorings.

[0005] Among aryl ketones, 3,4-methylenedioxypropiophenone, also known as 1-(1,3-benzodioxol-5-yl)-1-propanone, is an important compound and intermediate in the above fields.

[0006] European Patent No. 1140894 describes a method for preparing 5-(α-hydroxyalkyl)benzo[1,3]dioxole, which provides a step for preparing acyl derivatives. Specifically, the described method comprises a first step a) of preparing benzo[1,3]dioxole by reacting 1,2-dihydroxybenzene and methylene chloride in a suitable solvent, followed by step b) of reacting the benzo[1,3]dioxole thus obtained with propionic anhydride in the presence of perchloric acid as an acylation catalyst. The proposed acylation catalysts in this specification were ZnO, ZnCl2, FeCl2, FeCl3, FeSO4, Fe2(SO4)3, FeO, Fe2O3, H3PO4, and HClO4.

[0007] The drawbacks associated with this type of catalyst are reported in International Publication No. 2020 / 174271. This international application highlights that all of these catalysts are toxic and corrosive, generally generating large amounts of hydrochloric acid in the effluent, resulting in the generation of large amounts of sludge, and thus high levels of process contamination and environmental harm.

[0008] Therefore, this same document suggests the use of alkyl sulfonic acid to facilitate the separation of reusable unreacted carboxylic acids and unreacted substrates.

[0009] In Example 14 of International Publication No. 2020 / 174271, 3,4-methylenedioxypropiophenone is prepared by first adding methanesulfonic acid and propionic anhydride, followed by the addition of 3,4-methylenedioxybenzene after cooling. The reaction is maintained at 0°C to 5°C for 4 hours, and after the reaction is complete, the reaction mass is diluted with water, and the obtained 3,4-methylenedioxypropiophenone and unreacted 3,4-methylenedioxybenzene are extracted with toluene. The toluene layer is distilled to recover the unreacted 3,4-methylenedioxybenzene, and 3,4-methylenedioxypropiophenone with a gas purity of 98% is obtained. They also recover 63 g of propionic acid in the aqueous phase.

[0010] The method described therein teaches the use of an excess homogeneous catalyst, namely methanesulfonic acid, which needs to be recovered. In fact, this method provides extraction in water / toluene to recover not only the desired product (in toluene) but also the catalyst. The inventors studied this method and noted that the prior art method in International Publication No. 2020 / 174271, considering the use of an excess catalyst and very harsh reaction conditions (4 hours at 0-5°C), could yield a higher conversion rate of 3,4-methylenedioxybenzene to the target product. Furthermore, it is well known that methylsulfonic acid is corrosive to metals and difficult to handle even when used industrially.

[0011] 3,4 are aromatic cyclic ethers. -Me Dioxybenzene is also known to be characterized by partial deactivation of the ring due to the bending of the -CH2- group at the bridging position relative to two oxygen atoms (FT-IR Investigation of Methoxy Substituted Benzenes Adsorbed on Solid Acid Catalysts. J.Phys.Chem.C 2012,116,21308-21317.dx.doi.org / 10.1021 / jp3023056. "Anomeric Effect in 1,3-Dioxole: A Theoretical Study". J.Am.Chem.Soc.1996,118,9850-9854.). Therefore, strict and dramatic conditions are usually required for acylation reactions, such as those reported in International Publication No. 2020 / 174271.

[0012] Furthermore, as reported in paragraph

[0016] of International Publication No. 2018 / 150230, the acylation of alkylenedioxybenzene compounds using conventional methods results in the synthesis of the final product in low yield and low purity because the -O-(CH2)mO- rings of the reactants and products are highly susceptible to cleavage under acidic conditions.

[0013] Therefore, the object of the present invention is, firstly, to provide an economical, efficient, and environmentally friendly method for preparing 3,4-methylenedioxypropiophenone, also known as 1-(1,3-benzodioxol-5-yl)-1-propanone, thereby overcoming the shortcomings of prior art methods, and secondly, to acylate it in good yield and purity. [Overview of the Initiative]

[0014] Despite the fact that heterogeneous catalysts, particularly those based on sulfonated resins, are known to have very low activity in catalyzing substrate acylation, even with ring-opening heterocycles, many difficulties in the acylation of anisole have been reported, for example, as reported in “Perfluorinated nafion-modified SBA-15 material for catalytic acylation of anisole”, Applied Catalyst A: General F. Martinez, G. Morales, A. Martin, R van Grieken. The present inventors have found that heterogeneous catalysts of a specific particle size can catalyze the starting material, namely 3,4 -Me We found that this method not only increases the conversion rate from ethylenedioxybenzene but also increases its selectivity.

[0015] The inventors have found that, surprisingly, a specific size of the granules / particles of a particular sulfonation heterogeneous catalyst increases selectivity, which is normally reduced not only with an increase in the active surface area of ​​the heterogeneous catalyst particles / granules, but also with an increase in aromatic substrate conversion due to the acceleration of sequential reactions across the target product.

[0016] Therefore, surprisingly, the applicant has found that 3,4 -Me We have discovered an innovative family of heterogeneous catalysts with specific particle sizes that can be efficiently used for the acylation of ethylenedioxybenzene. These microparticle catalysts not only enhanced the conversion but also enabled the formation of closed heterocyclic substrates 3,4 -MeThe selectivity of the acylation reaction on the thylenedioxybenzene could also be enhanced.

[0017] Therefore, the present invention relates to a method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone, which includes a step of reacting with propionic anhydride in the presence of a bulk or supported catalyst, and the catalyst is selected from the group consisting of sulfonated crosslinked divinylbenzene resin, sulfonated crosslinked divinylbenzene resin partially exchanged with iron, zinc or gallium, perfluorinated sulfone resin, and perfluorinated sulfone resin partially exchanged with iron, zinc or gallium, and the catalyst has an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm as measured by DLS (dynamic light scattering) or a particle size analyzer. The following are some aspects of the present invention, although some may overlap with other descriptions. However, the present invention is not limited to the following. [1] A method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone, comprising the step of reacting 3,4-dimethyldioxybenzene with propionic anhydride in the presence of a bulk or supported catalyst, wherein the catalyst is selected from the group consisting of sulfonated crosslinked divinylbenzene resin, sulfonated crosslinked divinylbenzene resin partially replaced with iron, zinc or gallium, perfluorinated sulfonate resin, and perfluorinated sulfonate resin partially replaced with iron, zinc or gallium, and the catalyst has an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm, as measured by DLS (dynamic light scattering) or particle size measurement. [2] The bulk or supported catalyst is a sulfonated crosslinked polystyrene-divinylbenzene resin used as a bulk or supported on silica, wherein the sulfonated crosslinked polystyrene-divinylbenzene resin contains 2 to 6, preferably 2.5 to 5.5, and more preferably about 5 groups per gram of material. 3 The method according to [1], characterized by an acid load expressed as mmol of H. [3] The bulk or supported catalyst is a perfluorinated sulfonic acid resin used as a bulk or supported on silica, wherein the perfluorinated sulfonic acid resin contains 0.2 to 2, preferably 0.7 to 1.6, of the group-SO per gram of material. 3 The method according to [1], characterized by an acid loading amount expressed as mmol of H, more preferably about 1.2. [4] The method according to [2], wherein the sulfonated crosslinked polystyrene-divinylbenzene resin is the product Amberlyst. [5] The method according to [3], wherein the perfluorinated sulfonic acid resin is product Aquivion or product Nafion. [6] The method according to [1], wherein the bulk or supported catalyst is a sulfonated crosslinked polystyrene-divinylbenzene resin or a perfluorinated sulfonic acid resin partially replaced with iron, zinc, or gallium, and the partial replacement is a percentage of 5 to 80% of hydrogen atoms replaced with metal ions selected from Fe, Zn, and Ga, preferably the replacement percentage is 10 to 50%, and more preferably about 30%. [7] The method according to any one of [1] to [6], wherein the catalyst is supported on a suitable inorganic oxide, preferably zirconia, alumina, titania, and silica, more preferably silica. [8] The method according to [7], wherein the catalyst is supported on the inorganic oxide in an amount of 1 to 60 weight percent (%), more preferably 5 to 30 weight percent, and even more preferably 10 to 15 weight percent, relative to the total weight of the supported catalyst. [9] The method according to any one of [1], [3], [5] to [8], wherein the step of reacting 3,4-dimethyldioxybenzene with propionic anhydride is carried out in a temperature range of 50 to 200°C, preferably 60 to 150°C, and more preferably about 80°C.

[10] [[ID=No.50]]<No. = The method according to [9], wherein the reaction time is 5 to 240 minutes, preferably 5 to 120 minutes, and more preferably about 60 minutes.

[11] The method according to any one of [1], [2], [4], [6] to [8], wherein the step of reacting 3,4-dimethyldioxybenzene with propionic anhydride is carried out in a temperature range of 50 to 150°C, preferably 60 to 130°C, more preferably about 80°C or about 120°C.

[12] The method according to

[11] , wherein the reaction time is 5 to 240 minutes, preferably 5 to 120 minutes, and more preferably about 60 minutes.

[13] The method according to any one of [1], [3], [5] to

[10] , wherein the amount of the catalyst, expressed as the ratio of H+ or active sites per mole of limiting reagent, is 0.0001 to 1, preferably 0.001 to 0.04, and more preferably about 0.007.

[14] The method according to any one of [1], [2], [4], [6] to [8],

[11] to

[12] , wherein the amount of the catalyst, expressed as the ratio of H+ or active sites per mole of limiting reagent, is 0.002 to 1, more preferably 0.01 to 0.08, and even more preferably about 0.03.

[15] The method according to any one of [1] to

[14] , wherein the step of reacting 3,4-dimethyldioxybenzene with propionic anhydride is carried out in which the molar ratio between 3,4-dimethyldioxybenzene and propionic anhydride is in the range of 2 to 1:1 to 2, preferably a stoichiometric ratio of 1:1.

[16] The method according to any one of [1] to

[15] , wherein the catalyst is recovered, regenerated, and recycled.

[17] The method according to

[16] , wherein the catalyst is recovered by filtration from a suspension of the reaction medium and nitric acid aqueous solution at a concentration preferably in the range of 2% to 60% by weight, more preferably 10 to 40%, and even more preferably 20% by weight.

[18] The method according to

[16] , wherein the catalyst is recovered by filtration from a suspension of the reaction medium and hydrochloric acid in a diluted aqueous solution at a concentration preferably in the range of 2% to 30% by weight, more preferably 20% by weight.

[19] The method according to any one of

[16] to

[18] , wherein the recovery of the catalyst is carried out at a temperature in the range of room temperature to reflux for a period of time ranging from a few minutes to 4 hours, preferably 1 hour.

[20] The recovery, regeneration, and recycling of the catalyst are performed by H 2 O 2 The method described in

[16] , which is performed using

[16] .

[21] The method according to any one of [1] to

[20] , wherein the catalyst has an average particle size of 40 μm to 100 μm.

[22] The method according to any one of [1] to

[21] , wherein the method is a continuous method.

[0018] In this invention, when the term "particle size" is used, it refers to the average diameter of a single particle / granule of the final catalyst.

[0019] In an advantageous embodiment of the method of the present invention, the catalyst has an average particle size of 40 μm to 100 μm.

[0020] In preferred embodiments, the catalyst is a supported catalyst supported on an oxide, preferably silica, zirconia, titania, or alumina, and more preferably on silica.

[0021] Therefore, the inventors have surprisingly found that the use of bulk or supported resins characterized by the presence of sulfonic acid functional groups is due to propionic anhydride 3,4 -Me We noted that it exhibited specific catalytic activity in the acylation of ethylenedioxybenzene. Furthermore, we found that when the catalyst is in powder form and used as both a bulk catalyst and a supported catalyst, 3,4 -Me We noted that the acylation process of ethylenedioxybenzene was extremely efficient.

[0022] Advantageously, the catalyst of the method of the present invention can be recovered, regenerated, and recycled to restart the reaction.

[0023] The catalysts used herein are suitable for application in both batch and continuous flow systems and result in the selective formation of 3,4-methylenedioxypropiophenone.

[0024] In an advantageous embodiment, the method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone is a continuous method.

[0025] From the above, it is clear that the method of the present invention is extremely efficient for the production of 1-(1,3-benzodioxol-5-yl)-1-propanone, which has less stringent operating conditions and is environmentally friendly compared to the prior art method, and which also has the potential to act continuously. [Brief explanation of the drawing]

[0026] [Figure 1] Figure 1 shows the results of Example 7. [Figure 2] Figure 2 shows the results of Example 23. [Modes for carrying out the invention]

[0027] Therefore, the present invention relates to a method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone, wherein 3,4 are used in the presence of a bulk or supported catalyst. -MeThe present invention relates to a method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone, comprising the step of reacting ethylenedioxybenzene with propionic anhydride, wherein the catalyst is selected from the group consisting of sulfonated crosslinked divinylbenzene resin, sulfonated crosslinked divinylbenzene resin partially replaced with iron, zinc, or gallium, perfluorinated sulfone resin, and perfluorinated sulfone resin partially replaced with iron, zinc, or gallium, and the catalyst has an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm, as measured by DLS (dynamic light scattering) or particle size measurement.

[0028] In this invention, when the term "particle size" is used, it refers to the average diameter of a single particle / granule of the final catalyst.

[0029] In an advantageous embodiment of the method of the present invention, the catalyst has an average particle size of 40 μm to 100 μm.

[0030] The present invention relates to the use of a bulk or supported catalyst selected from the group consisting of sulfonated crosslinked divinylbenzene resin, sulfonated crosslinked divinylbenzene resin partially replaced with iron, zinc, or gallium, perfluorinated sulfone resin, and perfluorinated sulfone resin partially replaced with iron, zinc, or gallium, in the presence of a 3,4 -Me The process includes a step of acylation of ethylenedioxybenzene, and the catalyst has an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm, as measured by DLS (dynamic light scattering) or particle size analyzer.

[0031] All of these catalysts are defined as heterogeneous catalysts.

[0032] As will become clearer from the experimental portion, the inventors of 3,4 -MeAttempts were made to directly use commercially available heterogeneous catalysts when acyling ethylenedioxybenzene, but these attempts yielded very poor results, especially at low temperatures. The inventors have found that acyling of MDB is possible with surprising results when the catalyst has an average particle size of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm, as measured by DLS (dynamic light scattering) or particle size measurement.

[0033] The catalyst may be used as a bulk or as a sulfonated crosslinked polystyrene-divinylbenzene resin supported on silica. Preferably, the sulfonated crosslinked polystyrene-divinylbenzene resin is characterized by an acid loading expressed as mmol of group-SO3H per gram of material, in the range of 2 to 6, more preferably 2.5 to 5.5, and even more preferably about 5.

[0034] The catalyst may be a perfluorinated sulfonic acid resin used as a bulk material or supported on silica. Preferably, the perfluorinated sulfonic acid resin is characterized by an acid loading expressed as mmol of group-SO3H per gram of material in the range of 0.2 to 2, more preferably 0.7 to 1.6, and even more preferably the catalyst has an acid loading of about 1.2.

[0035] In a preferred embodiment, the catalyst described above is a commercially available catalyst used in the micronization process because it has a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm, as measured by DLS (dynamic light scattering) or a particle size analyzer.

[0036] Sulfonated crosslinked polystyrene-divinylbenzene resins are product Amberlyst and may be exchange ion resins available from Rohm and Haas Company. These resins may be named products as follows: Amberlyst15 (https: / / www.sigmaaldrich.com / catalog / product / aldrich / 216399), which has an acid load of -4.7 (expressed as mmol of the group -SO3H per gram of material), Amberlyst36, which has an acid load of -5.4 (expressed as mmol of the -SO3H group per gram of material), (Sibao Liu and others, 'Renewable Lubricants with Tailored Molecular Architecture', Science Advances, 5.2 (2019) (https: / / doi.org / 10.1126 / sciadv.aav5487)) Amberlyst39 (Tomasz Komon and others, 'Esterification of Acrylic Acid with 2-Ethylhexan-1-Ol: Thermodynamic and Kinetic Study', Applied Catalysis A:General, 451(2013), 127-36(https: / / doi.org / 10.1016 / j.apcata.2012.11.018)) has an acid loading of -5 (expressed as mmol of the -SO3H group per gram of material), or Amberlyst70 (Tomasz Komon and others, 'Esterification of Acrylic Acid with 2-Ethylhexan-1-Ol: Thermodynamic and Kinetic Study', Applied Catalysis A:General, 451 (2013), 127-36 (https: / / doi.org / 10.1016 / j.apcata.2012.11.018)) has an acid load of -2.55 (expressed as mmol of the -SO3H group per gram of material).

[0037] The perfluorinated sulfonic acid resin may be product Aquivion, which is a fully fluorinated resin having the following structure. [ka]

[0038] The presence of terminal-CF2CF2SO3H groups makes perfluorinated resins strongly acidic.

[0039] The resin Aquivion can be a commercially available product named Aquivion® PW79S, which is a crude acidic perfluorinated resin powder based on the short-chain (SSC) copolymer CF2=CF-O-(CF2)2-SO2F of tetrafluoroethylene and sulfonyl fluoride vinyl ether (SFVE), manufactured by Solvay, and has an acid load of 1.27.

[0040] The resin Aquivion can be a commercially available product named Aquivion® P98-S, which is a perfluorinated pellet in sulfonyl fluoride (-SO2F) form exhibiting an equivalent weight (EW) of 980 g / eq. This perfluorinated resin is based on the unique short-side-chain copolymer CF2=CF-O-(CF2)2-SO2F of tetrafluoroethylene (TFE) and sulfonyl vinyl fluoride (SFVE), manufactured by Solvay, and has an acid loading expressed as mmol of 1.02 groups of -SO3H per gram of material.

[0041] The resin Aquivion may be a commercially available product named Aquivion® PW87-S and is a perfluorinated resin in powder form. This perfluorinated resin is based on the unique short-side-chain copolymer CF2=CF-O-(CF2)2-SO2F of tetrafluoroethylene (TFE) and sulfonyl vinyl fluoride (SFVE), manufactured by Solvay, and has an acid loading of 1.15, expressed as mmol of the -SO3H group per gram of material.

[0042] The use of other resins such as Aquivion, which are available on the market or in the experimental section of this invention, is intended in accordance with the present invention.

[0043] The perfluorinated sulfonic acid resin may be the product Nafion, which is a fully fluorinated resin having the following structure. [ka]

[0044] Nafion's unique ionic properties result from the incorporation of sulfonate-terminated perfluorovinyl ether groups into a tetrafluoroethylene (PTFE) skeleton. The resin Nafion is a commercially available perfluorosulfonic acid Nafion resin in pellet form, possessing high thermal stability and chemical resistance, and is named Nafion® NR50. This perfluorinated resin is manufactured by DuPont and has an acid loading expressed as 0.8 mmol of -SO3H groups per gram of material.

[0045] The use of Nafion, a resin available on the market or similar to that used in this experimental portion, is intended in accordance with the present invention.

[0046] Therefore, the heterogeneous catalyst of the present invention is characterized by the presence of sulfonic acid groups, which can be partially or completely replaced with iron, zinc, or gallium.

[0047] In fact, the catalytic materials (acid resins) reported herein can be modified by exchanging acidic protons with metal ions selected from iron (Fe), zinc (Zn), and gallium (Ga). Procedures used to exchange hydrogen ions on sulfonated crosslinked polystyrene-divinylbenzene resins or perfluorinated sulfonic acid resins are reported in the literature, e.g., Journal of Molecular Catalysis A:Chemical 411 (2016) 257-263).

[0048] Surprisingly, catalyst modifications in terms of acid site density, intensity, and accessibility due to the presence of metal ions Fe, Zn, or Ga strongly influence the reactivity of MDB in terms of conversion rate and selectivity to the product.

[0049] In the present invention, when the sulfonated resin catalyst is replaced, it is replaced only partially.

[0050] According to the present invention, partial exchange means a percentage of 5 to 80% of hydrogen atoms with a metal ion selected from Fe, Zn, and Ga. Preferably, the exchange percentage is 10 to 50%, and more preferably about 30%.

[0051] An example of a resin partially replaced with Fe can be prepared by using Aquivion PW87-S in powder form, according to the above-mentioned literature.

[0052] Therefore, the final exchange sulfonation catalyst is subjected to a particle size reduction step and, as measured by DLS (dynamic light scattering) or particle size measurement, has a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm. The above-mentioned material can be used as a catalyst in the method of the present invention, supplied or supported on a suitable inorganic oxide.

[0053] Suitable inorganic oxides may be silica, zirconia, titania, and alumina, with silica being preferred. In particular, the supported material may be a commercially available product or may be prepared as described in the literature, for example, as described in Italian Patent No. 102018000006967.

[0054] Therefore, the catalyst can be supported according to a general procedure known in the art. A preferred procedure for preparing the supported catalyst according to the present invention is reported as an example in the experimental section.

[0055] The aforementioned resins, named Amberlyst, Aquivion, and Nafion, can be supported on suitable inorganic oxides. For example, Aquivion D79 can be supported on zirconia or silica, and Aquivion PW98-S can be supported on alumina. Nafion supported on silica is also available on the market from Dupont or Merk.

[0056] The resin used as a catalyst in the present invention can be supported on an inorganic oxide, preferably silica, alumina, titania, and zirconia, in an amount of 1 to 60 weight percent (%), more preferably 5 to 30 weight percent, and even more preferably 10 to 15% of the total weight of the supported catalyst.

[0057] The final supported sulfonation catalyst during the synthesis process is shaped to obtain a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm, by measuring with DLS (dynamic light scattering) or a particle size analyzer.

[0058] In a preferred embodiment, the catalyst used in the present invention is -Sulfonated crosslinked divinylbenzene resins partially replaced with iron, zinc, or gallium and supported on inorganic oxides, or - Perfluorinated sulfone resins supported on inorganic oxides, partially replaced with iron, zinc, or gallium.

[0059] The final supported exchange sulfonation catalyst during the synthesis process is shaped to obtain a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, and more preferably 1 μm to 100 μm, by measuring with DLS (dynamic light scattering) or a particle size analyzer.

[0060] In one embodiment of the method of the present invention, a perfluorinated sulfone resin, selected from the group consisting of perfluorinated sulfone resins and perfluorinated sulfone resins partially replaced with iron, zinc, or gallium, is subjected to a prior micronization step or produced with a particle size within the precise range according to the present invention (measured by DLS (dynamic light scattering) or a particle size analyzer, with a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm), is used in the presence of a bulk or supported catalyst, 3,4 -MeThe step of reacting ethylenedioxybenzene with propionic anhydride is carried out at a temperature range of 50 to 200°C, more preferably 60 to 150°C, and even more preferably about 80°C. In this embodiment of the present invention, the reaction time is 5 to 240 minutes, more preferably 5 to 120 minutes, and even more preferably about 60 minutes.

[0061] In one embodiment of the method of the present invention, a sulfonated crosslinked divinylbenzene resin, a sulfonated crosslinked divinylbenzene resin partially replaced with iron, zinc, or gallium, is selected from the group, which has been subjected to a prior micronization step or has been produced with a particle size within the precise range according to the present invention (measured by DLS (dynamic light scattering) or a particle size analyzer, with a particle size in the range of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm), in the presence of a bulk or supported catalyst, 3,4 -Me The step of reacting ethylenedioxybenzene with propionic anhydride is carried out at a temperature range of 50 to 150°C, more preferably 60 to 130°C, and even more preferably about 80°C or 120°C. In this embodiment of the present invention, the reaction time is 5 to 240 minutes, more preferably 5 to 120 minutes, and even more preferably about 60 minutes.

[0062] In a preferred embodiment, the method is carried out in a batch reactor, more preferably under solvent-free conditions, by adding a pure catalytic amount of catalyst.

[0063] The amount of catalyst is generally 3,4 -Me This is expressed as the molar ratio of H+ or active sites per mole of the limiting reagent, which is ethylenedioxybenzene.

[0064] For bulk or supported catalysts selected from the group consisting of perfluorinated sulfone resins and perfluorinated sulfone resins partially replaced with iron, zinc, or gallium, the ratio is preferably 0.0001 to 1, more preferably 0.001 to 0.04, and even more preferably about 0.007.

[0065] In the case of a bulk or supported catalyst selected from the group of sulfonated crosslinked divinylbenzene resins, the ratio of sulfonated crosslinked divinylbenzene resin partially replaced with iron, zinc, or gallium is 0.002 to 1, more preferably 0.01 to 0.08, and even more preferably about 0.03.

[0066] To have an advantage, 3, 4 -Me The step of reacting ethylenedioxybenzene with propionic anhydride is preferably 3,4 in the range of 2 to 1 to 1 to 2. -Me The process is carried out in a molar ratio between ethylenedioxybenzene and propionic anhydride, more preferably in a stoichiometric ratio of 1:1.

[0067] A stoichiometric ratio is preferable, and therefore, it is not necessary to consistently have an excess of one of the two reagents.

[0068] In advantageous embodiments, the catalyst of this method can be recovered, regenerated, and recycled.

[0069] In preferred embodiments, the catalyst can be recovered by filtration from the suspension in the reaction medium and a diluted aqueous solution of nitric acid at a concentration preferably in the range of 2% to 60% by weight, more preferably 10% to 40%, and even more preferably 20% by weight.

[0070] In another preferred embodiment, the catalyst can be recovered by filtration from the suspension in the reaction medium and a diluted aqueous solution of hydrochloric acid at a concentration preferably in the range of 2% to 30% by weight, more preferably 20% by weight.

[0071] Catalyst recovery is preferably carried out at a temperature in the range of room temperature to reflux, over a period of several minutes to 4 hours, more preferably 1 hour.

[0072] Therefore, catalyst recovery is a regeneration process. After the regeneration process, the catalyst is recovered by filtration, washed with water until the mother liquor reaches a neutral pH, and dried at approximately 120°C for approximately 1 hour. The material thus obtained, i.e., the catalyst of the present invention, can be recycled for other reactions.

[0073] Furthermore, the catalyst materials reported herein are suitable for application in both batch and continuous flow apparatuses and result in the selective formation of 3,4-methylenedioxypropiophenone.

[0074] Therefore, the inventors have noted that, surprisingly, the use of bulk or supported resins having granules / particles within a specific size range and characterized by the presence of sulfonic acid functional groups exhibits specific catalytic activity in the acylation of 3,4-methylenedioxybenzene with propionic anhydride. Furthermore, the inventors have noted that when the catalyst is used as both a bulk catalyst and a supported catalyst, and is in the form of a powder having a particle size range of 1 μm to 300 μm, preferably 1 μm to 180 μm, more preferably 1 μm to 100 μm as measured by DLS (dynamic light scattering) or particle size measurement, 3,4 -Me Even with a very small amount of reactive starting material as ethylenedioxybenzene, 3,4 -Me We noted that the method for acylation of ethylenedioxybenzene was extremely efficient.

[0075] Advantageously, the catalyst of the method of the present invention can be recovered, regenerated, and recycled to restart the reaction.

[0076] In an advantageous embodiment, the method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone is a continuous method.

[0077] From the above, it is clear that the method of the present invention is extremely efficient for the production of 1-(1,3-benzodioxol-5-yl)-1-propanone, not only because the operating conditions are less stringent and environmentally friendly compared to the solvent-free conditions of the prior art method, but also because it has the potential to act continuously. Surprisingly, the method of the present invention does not require one of the two reagents to be consistently in excess, and exhibits a short reaction time and a relatively low reaction temperature. This method is further characterized by the easy recovery, regeneration, and recycling of the catalyst.

[0078] While not bound by any particular theory, the inventors consider it fundamentally important to include the possibility of supporting this heterogeneous catalyst on a suitable support having a high pore volume and / or a high surface area.

[0079] The features and advantages of the present invention will also become clearer from the following non-limiting examples.

[0080] Experimental section The following acronyms were used to indicate the components / products / effects in the experimental section: MBD = 3,4-methylenedioxybenzene AP = Propionic anhydride MDP1P = 3,4-methylenedioxypropiophenone X = conversion rate Y = Yield S = Selectivity

[0081] Example 1: Acylation of MDB using commercially available Aquivion PW87 2.126 grams of 3,4-methylenedioxybenzene (MBD) and 2.2924 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0988 grams of commercially available catalyst (Aquivion PW87-S, corresponding to the molar ratio between the active acid site and MDB equal to 0.007), with a particle size in the range of 0.6 mm to 1.1 mm as measured by DLS (dynamic light scattering) or particle size analyzer, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in an 80°C preheated oil bath and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: 40% MDB conversion rate, 64% propionic anhydride conversion, 26% 3,4-methylenedioxypropiophenone yield, and 64% selectivity.

[0082] Example 2 Preparation of 3,4-methylenedioxypropiophenone with the catalyst Aquivion PW87-S at 80°C for 1 hour according to the present invention 2.126 grams of 3,4-methylenedioxybenzene (MBD) and 2.2924 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0988 grams of catalyst (Aquivion PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in an 80°C preheated oil bath and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: 50% MDB conversion rate, 77% propionic anhydride conversion, 41% 3,4-methylenedioxypropiophenone yield, and 82% selectivity.

[0083] Therefore, the inventors noted that when the catalyst is of a specific granule / particle size according to the present invention, it enables not only a higher conversion rate of the initial product but also an unexpectedly higher selectivity by reducing the catalyst particle size.

[0084] Example 3 Effect of particle size on catalytic activity of Aquivion PW87 By changing only the catalyst particle size, we investigated the effect of catalyst particle size on the catalytic activity of MDB acylation, as described in Example 2. The results are reported in Table X below. [Table X]

[0085] Catalyst particle size plays a fundamental role in the reaction. Reducing particle size resulted in an improvement in MDB conversion rate, which is primarily dependent on the catalytically active surface (and increases as particle size decreases). Surprisingly, reducing catalyst particle size also significantly improved reaction selectivity for MDP1P.

[0086] Example 4 Evaluation of temperature effects in the presence of catalyst Aquivion PW87-S The other four reactions were carried out as described in Example 2, by changing only the reaction temperature, i.e., 60°C, 80°C, 100°C, and 120°C. The results are reported in Table 1. [Table 1]

[0087] Similar to Example 2, the reaction conditions were as follows: molar ratio between the active acid site and MDB equal to 0.007; MDB:AP = 1:1; reaction time 1 hour.

[0088] It should be noted that while increasing the reaction temperature resulted in an increase in the conversion rates of both reagents (as expected from the acceleration of the reaction kinetics), the increase in MDP1P yield was not linear, and therefore a slight decrease in selectivity was observed, promoting the formation of by-products (such as polyalkylation).

[0089] In any case, all temperatures were efficient in achieving a high yield that was commensurate with the selectivity achieved.

[0090] Example 5 Scaling up to 40 ml test 20.21 grams of MDB and 21.74 grams of propionic anhydride were placed in a 250 mL three-necked round-bottom flask and stirred to obtain a homogeneous solution. The reagent mixture was heated in an oil bath at 80°C, and then 0.9363 grams of catalyst (Aquivion PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-micronized to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into a flask equipped with two condensers and a thermometer. The reaction was carried out for 1 hour under magnetic stirring (720 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 500 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 53% MDB conversion rate, 82% propionic anhydride conversion, 43% 3,4-methylenedioxypropiophenone yield, and 81% selectivity.

[0091] (Compared to Example 1) we showed that increasing the x10 coefficient did not affect either the conversion rate or the yield.

[0092] Example 6 Scaled up to 400mL 202.16 grams of MDB and 217.22 grams of propionic anhydride were placed inside a 1 L jacketed reactor equipped with a mechanical stirrer, reflux condenser, and thermometer. The reagent mixture was heated to 80°C, after which 9.3586 grams of catalyst (Aquivion PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted. The reaction was carried out for 1 hour under mechanical stirring (250 rpm). After the reaction, 2 mL of the reaction mixture was sampled and separated from the catalyst by filtration. 50 μL of the mixture was diluted with 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatographic quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 46% MDB conversion rate, 71% propionic anhydride conversion, 38% 3,4-methylenedioxypropiophenone yield, and 82% selectivity.

[0093] Example 7 Evaluation of the reaction time effect of PW87-S in the reaction described in Example 6. To investigate the effect of reaction time in larger reactors, the reaction was repeated as described in Example 5. To do this, the reaction mixture was sampled at different times, as reported in Example 5. The results are reported in Table 2 and shown in Figure 1. [Table 2]

[0094] By sampling the reaction mixture at different times, it was possible to confirm that the selectivity for the desired product did not change during the reaction. Conversion increased with reaction time as the yield of the desired product. The best compromise between yield and reaction time was 1 hour, but it was possible to obtain almost the same results by stopping the reaction after 30 minutes. In the latter case, the conversion rate of MDB and the yield in the product were a few percent lower, but it was possible to increase the overall yield by doubling the number of catalyst cycles per day. Increasing the reaction time up to 2 hours made it possible to increase the conversion rate and yield without reducing selectivity, thereby reducing the amount of reactants that had to be recycled.

[0095] Example 8 Evaluation of preferred conditions when Aquivion PW79 is used as a catalyst. 2.1305 grams of MDB and 2.2879 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0900 grams of catalyst (Aquivion PW79, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 64% MDB conversion rate, 92% propionic anhydride conversion, 47% 3,4-methylenedioxypropiophenone yield, and 73% selectivity.

[0096] Example 9 Acylation of MDB using commercially available catalyst Aquivion PW98 2.1307 grams of MDB and 2.2879 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1117 grams of commercially available catalyst (Aquivion PW98, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) with a particle size ranging from 1.4 mm to 2.4 mm, as measured by a particle size analyzer, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 100 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 11% MDB conversion rate, 18% propionic anhydride conversion, 7% 3,4-methylenedioxypropiophenone yield, and 55% selectivity.

[0097] Example 10 Acylation of MDB using the catalyst Aquivion PW98 according to the present invention 2.1307 grams of MDB and 2.2879 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1117 grams of catalyst (Aquivion PW98, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 100 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 40% MDB conversion rate, 64% propionic anhydride conversion, 29% 3,4-methylenedioxypropiophenone yield, and 72% selectivity.

[0098] Example 11 The present invention using the catalyst Aquivion D79 supported on silica 2.1282 grams of MDB and 2.2860 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.2999 grams of catalyst (30% Aquivion D79 relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) characterized by a particle size in the range of 40 μm to 100 μm, as measured by DLS (dynamic light scattering) or particle size measurement, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column and a flame ionization detector (FID). The results were as follows: 65% MDB conversion rate, 95% propionic anhydride conversion, 47% 3,4-methylenedioxypropiophenone yield, and 72% selectivity.

[0099] Example 12 General procedure for laboratory-scale catalyst regeneration in the method of the present invention First, the catalyst was separated from the reaction solution by filtration using a Buchner funnel fitted with a filter aid. Considering 0.1 g of exhaust catalyst, it was washed with acetone HPLC (25 mL) to remove all weakly adsorbed reactants and residual products after the reaction, and then finely ground in a mortar. The catalyst was then placed inside a flask equipped with two condensers. Next, the catalyst was regenerated under reflux for 1 hour using 5 mL of 20 wt% HNO3 (or HCl) solution. The resulting suspension was then cooled and separated from the solution by filtration using a Buchner funnel fitted with a filter aid. The catalyst was washed with water to a neutral pH and then washed again with acetone HPLC. Before catalyst testing, the catalyst was dried in an oven at 120°C for 1 hour.

[0100] Example 13 Recycling test using catalyst PW87-S, regeneration with nitric acid The catalyst from Example 5 was regenerated at 100°C for 1 hour using 50 mL of HNO3 20% w / w solution, similar to Example 12.

[0101] 13.61 grams of MDB and 14.57 grams of propionic anhydride were placed in a 250 mL three-necked round-bottom flask and stirred to obtain a homogeneous solution. The reagent mixture was heated in an oil bath at 80°C, and then 0.6299 grams of regenerated catalyst (Aquivion PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into a flask equipped with two condensers and a thermometer. The reaction was carried out for 1 hour under magnetic stirring (720 rpm). After the reaction, 2 mL of the reaction mixture was sampled and separated from the catalyst by filtration. 50 μL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID).

[0102] To test the recyclability of the material through several catalytic cycles, the catalyst recovery and regeneration described in Example 12 were performed five times. The results are reported in Table 3 below. [Table 3]

[0103] By using nitric acid, which offers clear advantages in terms of process efficiency, the catalyst was recovered and recycled several times.

[0104] Example 14 Recycling test using catalyst Aquivion PW87-S, regeneration with hydrochloric acid 2.1284 grams of MDB and 2.2935 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0990 grams of catalyst (Aquivion PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The catalyst was then regenerated at 100°C for 1 hour with 5 mL of 20% w / w HCl solution, as in Example 12, recovered, washed, dried as previously reported, and tested under the same conditions for the acylation reaction. The results are reported in Table 4 below. [Table 4]

[0105] The catalyst was recovered and recycled by using hydrochloric acid, which offers clear advantages in terms of process efficiency.

[0106] Example 15 Effect of the molar ratio between reagents on the catalyst Aquivion PW87-S, which has been micronized according to the present invention. The other four reactions, as described in Example 2, were performed by changing only the molar ratio (mol MDB / mol AP) between reagents in the ranges of 1:1, 1.4:1, 2:1, and 1:2. The results are reported in Table 5 below. [Table 5]

[0107] An excess increase in AP is 3,4 -Me While a higher conversion rate to ethylenedioxybenzene was obtained, it had a detrimental effect on selectivity; on the other hand, working with a slightly excess of MDB resulted in more selective conversion of AP to the target product. In either case, the best compromise between MDB conversion rate and selectivity for the MDP1P product was stoichiometric amounts of reagent.

[0108] Example 16 Effect of catalyst loading by Aquivion PW87-S as a function of the molar ratio between the active acid site and the limiting reagent. The other three reactions were carried out as described in Example 2, by changing only the molar ratio between the active acid site and the limiting reagent, i.e., 0.003, 0.007, and 0.014. The catalyst was subjected to a particle size reduction process and measured by DLS (dynamic light scattering) or particle size analyzer to obtain a particle size in the range of 40 μm to 100 μm. The results are shown in Table 6 below. [Table 6]

[0109] Increasing the amount of catalyst supported accelerated the conversion of our reagent, resulting in only a slight decrease in product selectivity.

[0110] Example 17 Zn-exchanged Aquivion D79 supported on silica. Supported Aquivion D79, characterized by a particle size in the range of 40 μm to 100 μm as measured by DLS (Dynamic Light Scattering) or particle size measurement, is Zn, specifically Zn 2+ The reaction was carried out as described in Example 9 by replacing it with 100%. The results are shown in Table 7 below. [Table 7]

[0111] It was found that 100% exchange with Zn had an undesirable effect on the reaction.

[0112] Therefore, the inventors have found that it is possible to acylate MDB using only catalysts having partial exchange, as shown in Example 18 below. The partial exchange of the catalyst according to the present invention is a percentage of 5 to 80% of hydrogen atoms exchanged with metal ions selected from Fe, Zn, and Ga, preferably an exchange percentage of 10 to 50%, more preferably about 30%.

[0113] Example 18 Fe replacement for Aquivion PW87-S Other reactions include Aquivion PW87-S and Fe:Fe 3+ Replace 50% with Fe 3+ The reaction was carried out at 80°C or 120°C as described in Example 2, by 100% replacement. The final catalyst was characterized by a particle size in the range of 40 μm to 100 μm, measured by DLS (dynamic light scattering) or particle size measurement. After the first cycle of the reaction, the catalyst was recovered, washed with 2-propanone, and repeated. The results are reported in Table 8 below. [Table 8]

[0114] When Aquivion is partially exchanged with an ion as Fe or Zn, the conversion rate of MDB decreases sharply, but the selectivity increases.

[0115] Example 19 Effects of catalyst shape Catalyst form: Only the powder (Aquivion PW98) and pellet (8-14 mesh, Aquivion P98) were changed, and the other reactions were carried out at 120°C as described in Example 9. The sole forming agent was subjected to a micronization process to a particle size in the range of 40 μm to 100 μm, measured by DLS (dynamic light scattering) or particle size analyzer. The results are reported in Table 9 below. [Table 9]

[0116] Surprisingly, when the catalyst having the particle size according to the present invention was used in pellets of 8 to 14 mesh, it showed better results in terms of yield, conversion rate, and selectivity compared to the same catalyst.

[0117] Example 20 Recycling test using Aquivion PW79, regeneration with nitric acid. 2.1303 grams of MDB and 2.2947 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0903 grams of catalyst (Aquivion PW79, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID).

[0118] After the initial run, the catalyst was regenerated at 100°C for 1 hour using 5 mL of 20% w / w HNO3 solution, as in Example 12, then recovered, washed, dried, and finally tested under the same conditions as above. The results are reported in Table 10 below. [Table 10]

[0119] By using nitric acid, which offers clear advantages in terms of process efficiency, the catalyst was recovered and recycled several times.

[0120] Example 21 Recycling test using Aquivion PW79, regeneration with hydrochloric acid. 2.1288 grams of MDB and 2.2972 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.0902 grams of catalyst (Aquivion PW79, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID).

[0121] After the initial run, the catalyst was regenerated at 100°C for 1 hour using 5 mL of a 20% w / w HCl solution, as in Example 12, then recovered, washed, dried, and finally tested under the same conditions as above. The results are reported in Table 11 below. [Table 11]

[0122] The catalyst was recovered and recycled by using nitric acid, which offers clear advantages in terms of process efficiency.

[0123] Example 22 Acylation of MDB using a commercially available Amberlyst39 catalyst with a particle size of 200-300 μm. 2.1284 grams of MDB and 2.2822 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1003 grams of commercially available catalyst (Amberlyst39, corresponding to a molar ratio of 0.029 between the active acid moiety and MDB) with a particle size in the range of 200 μm to 300 μm, as measured by DLS (dynamic light scattering) or particle size measurement, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: MDB conversion rate of 42%, propionic anhydride conversion of 65%, 3,4-methylenedioxypropiophenone yield of 29%, and selectivity of 69%.

[0124] Example 23 Acylation and recycling tests of MDB using finely atomized Amberlyst30 catalyst, and regeneration with nitric acid. 2.1284 grams of MDB and 2.2822 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1003 grams of catalyst (Amberlyst39, corresponding to a molar ratio of 0.029 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). After the first run, the catalyst was regenerated at 100°C for 1 hour with 5 mL of 20% w / w HNO3 solution as in Example 12, recovered, washed, dried, and finally tested under the same conditions as above. The results are reported in Table 12 below and shown in Figure 2. [Table 12]

[0125] By using hydrochloric acid, which offers clear advantages in terms of process efficiency, the catalyst was recovered and recycled several times.

[0126] By using the catalyst within a preferred particle size range, higher conversion and better selectivity were achieved.

[0127] Example 24 Acylation of MDB using a commercially available Nafion NR50 catalyst with a particle size of 400-600 μm 2.1274 grams of MDB and 2.2815 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1419 grams of commercially available catalyst (Nafion NR50, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) with a particle size ranging from 400 μm to 600 μm, as measured by particle size analyzer, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: 20% MDB conversion rate, 29% propionic anhydride conversion, 11% 3,4-methylenedioxypropiophenone yield, and 56% selectivity.

[0128] Example 25 Acylation of MDB using Nafion NR50 catalyst having particle size according to the present invention As a general procedure, 2.1274 grams of MDB and 2.2815 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1419 grams of catalyst (Nafion NR50, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 150 μm to 300 μm, was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in a preheated oil bath at 120 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10.00°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). After the initial run, the catalyst was regenerated at 100°C for 1 hour with 5 mL of 20% w / w HNO3 solution as in Example 12, recovered, washed, dried, and finally tested under the same conditions as above. The results are reported in Table 13 below. [Table 13]

[0129] The inventors noted that the catalyst according to the present invention enables better conversion rates, yields, and selectivity compared to the same catalyst that has not been atomized within the scope of the present invention.

[0130] Example 26 Catalyst testing under continuous flow conditions Catalyst testing was performed in a fixed-bed laboratory-scale reactor operating under continuous flow at atmospheric pressure. First, 0.1799 grams (0.4 ml) of catalyst (Aquivion PW79), pre-micronized to a particle size range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement, mixed with carborundum (total volume 0.6 mL), was inserted into a reactor made of 1 / 4-inch stainless steel tubing (quartz wool was provided at the beginning and end of the reactor). The reactor was wrapped with a heating band and finally covered with an insulating ceramic cloth bandage. Once the system reached a temperature of 150°C, the reagent mixture (consisting of 26.007 grams of MDB and 28.631 grams of propionic anhydride) (1 / 1 mol / mol) was supplied at 0.05 mL / min through a high-precision HPLC pump. The reaction time was started from when the first droplet of the mixture exited the system's outlet line. Samples were taken every 10 minutes. From each sample, 50 μL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280 °C at a rate of 10.00 °C / min after 6 minutes at 35 °C) and a flame ionization detector (FID). Results corresponding to the relevant time points are reported in Table 14 below. [Table 14]

[0131] The catalyst test, conducted in a flowing state, primarily aimed to cover this technical solution for the application of solid acid resins. The test demonstrated that the method of the present invention can be carried out advantageously in a continuous manner.

[0132] Example 27 Regeneration of the PW87 catalyst using H2O2 2.1417 grams of MDB and 2.2994 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.1004 grams of catalyst (AQUIVION PW87-S, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) that had been pre-processed to a particle size in the range of 40 μm to 100 μm by DLS (dynamic light scattering) or particle size measurement was inserted into the liquid mixture, and two condensers were attached to the flask. Next, the reaction mixture was placed in an 80°C preheated oil bath and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). Subsequently, the catalyst was regenerated at 100°C for 20 minutes using 5 mL of 30% w / w H2O2 solution instead of mineral acid, as described in Example 9, recovered, washed, dried, and tested for acylation under the same conditions. The results are reported in Table 15 below.

[0133] [Table 15] The catalytic activity was restored, offering a clear advantage in terms of process efficiency.

[0134] Example 28 General preparation procedure for supported catalysts using Aquivion (D72 or D79, or D82 or D98) A mixture of Si(MeO)4, distilled water, and 0.04 M HCl, each in a weight ratio of 68:11:1, was stirred for 45 minutes to obtain a clear solution. An Aquivion dispersion (D72 or D79, or D82 or D98) (for example, containing 25% w / w resin in water or a mixture of water and alcohol) was diluted with water or water and alcohol. A 0.4 M NaOH aqueous solution was added to the resin-containing solution while stirring. The silicon-containing solution prepared as described above was quickly added to the stirred resin / NaOH solution, and a solid gel was formed a few seconds after mixing. The solid was dried overnight in an oven at 95°C. After grinding, the obtained powder was re-acidified by stirring with an appropriate amount of 3.5 M HCl aqueous solution, and then washed with deionized water. This process was repeated four times. The catalyst was then treated overnight with 25% w / w HNO3 at 75°C, washed with deionized water, and dried at 100°C for 12 hours.

[0135] Example 29 Synthesis of a catalyst containing 13% by weight of Aquivion supported on silica. A mixture of 12.6706 g of Si(MeO)4, 2.0497 g of distilled water, and 0.1863 g of 0.04 M HCl was stirred for 45 minutes to obtain a clear solution. A mixture of 2.9712 g of Aquivion D72 (or D79, or D82, or D98) resin solution (containing 25% w / w resin), 8 g of distilled water, and 9.96 g of 1-propanol was prepared. 10.3 mL of 0.4 M NaOH aqueous solution was added to the resin-containing solution while stirring. The silicon-containing solution prepared as described above was quickly added to the stirred resin / NaOH solution, and a solid gel was formed a few seconds after mixing. The solid was dried overnight in a 95°C oven. After grinding, the resulting powder with a particle size of 40 μm to 100 μm was re-acidified by stirring with 50 mL of 3.5 M HCl aqueous solution, and then washed with deionized water. This process was repeated four times. Next, the catalyst was treated overnight at 75°C with 25% w / w HNO3, washed with deionized water, and dried at 100°C for 12 hours.

[0136] Example 30 Synthesis of a catalyst containing 13% by weight of Nafion supported on silica. A mixture of 7.6003 g of Si(MeO)4, 1.2306 g of distilled water, and 0.1112 g of 0.04 M HCl was stirred for 45 minutes to obtain a clear solution. A mixture of 2.2284 g of Nafion resin solution (containing 20% ​​w / w resin), 3.34 g of distilled water, and 4.16 g of 1-propanol was prepared. 5.52 mL of 0.4 M NaOH aqueous solution was added to the resin-containing solution while stirring. The silicon-containing solution prepared as described above was quickly added to the stirred resin / NaOH solution, and a solid gel was formed a few seconds after mixing. The solid was dried overnight in a 95°C oven. After grinding, the resulting powder with a particle size of 40 μm to 100 μm was re-acidified by stirring with 50 mL of 3.5 M HCl aqueous solution, and then washed with deionized water. This process was repeated four times. Next, the catalyst was treated overnight at 75°C with 25% w / w HNO3, washed with deionized water, and dried at 100°C for 12 hours.

[0137] Example 31 The present invention relates to a process using the catalyst Aquivion D72 supported in silica. 2.1458 grams of MDB and 2.3081 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.6726 grams of catalyst (Aquivion D72 13% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB), prepared with particle sizes ranging from 40 μm to 100 μm, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: 59% MDB conversion rate, 90% propionic anhydride conversion, 50% 3,4-methylenedioxypropiophenone yield and 85% selectivity, and 9% by-product yield.

[0138] Example 32 The present invention relates to acylation using the catalyst Aquivion D79 supported on silica. 2.1354 grams of MDB and 2.2956 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.7448 grams of catalyst (Aquivion D79 13% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB), prepared with particle sizes ranging from 40 μm to 100 μm, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used was 35°C for 6 minutes followed by heating to 280°C at a rate of 10°C / min) and a flame ionization detector (FID). The results were as follows: 50% MDB conversion rate, 85% propionic anhydride conversion, 43% 3,4-methylenedioxypropiophenone yield and 86% selectivity, and 7% by-product yield.

[0139] Example 33 The present invention relates to acylation using the catalyst Aquivion D83 supported on silica. 2.1402 grams of MDB and 2.3039 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.7754 grams of catalyst (Aquivion D83 13% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB), prepared with particle sizes ranging from 40 μm to 100 μm, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used was 35°C for 6 minutes followed by heating to 280°C at a rate of 10°C / min) and a flame ionization detector (FID). The results were as follows: 51% MDB conversion rate, 86% propionic anhydride conversion, 42% 3,4-methylenedioxypropiophenone yield and 83% selectivity, and 7% by-product yield.

[0140] Example 34 The present invention relates to a process using the catalyst Aquivion D98 supported in silica. As a general procedure, 1.0673 grams of MDB and 1.1502 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.4589 grams of catalyst (Aquivion D98 13% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB), prepared with particle sizes ranging from 40 μm to 100 μm, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used was 35°C for 6 minutes followed by heating to 280°C at a rate of 10°C / min) and a flame ionization detector (FID). The results were as follows: 49% MDB conversion rate, 86% propionic anhydride conversion, 42% 3,4-methylenedioxypropiophenone yield, 85% selectivity, and by-products.

[0141] Example 35 The present invention relates to a process using the catalyst Aquivion D72 (5% w / w) supported in silica. As a general procedure, 2.146 grams of MDB and 2.3044 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 1.762 grams of catalyst (Aquivion D72 5% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) prepared with particle sizes ranging from 40 μm to 100 μm, as described in Example 29 with modified resin loading, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatographic quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used was 35°C for 6 minutes followed by heating to 280°C at a rate of 10°C / min) and a flame ionization detector (FID). The results were as follows: 39% MDB conversion rate, 96% propionic anhydride conversion, 33% 3,4-methylenedioxypropiophenone yield and 86% selectivity, and 3% by-product yield.

[0142] Example 36 The present invention relates to a process using the catalyst Aquivion D72 (30% w / w) supported in silica. As a general procedure, 2.152 grams of MDB and 2.3269 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.2941 grams of catalyst (Aquivion D72 30% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid moiety and MDB) prepared with particle sizes ranging from 40 μm to 100 μm, as described in Example 29 with modified resin loads, were inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatographic quantification. Product analysis at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used was 35°C for 6 minutes followed by heating to 280°C at a rate of 10°C / min) and a flame ionization detector (FID). The results were as follows: 47% MDB conversion rate, 78% propionic anhydride conversion, 42% 3,4-methylenedioxypropiophenone yield and 88% selectivity, and 8% by-product yield.

[0143] Example 37 The present invention relates to a method using the catalyst Nafion (13% w / w) supported in silica. As a general procedure, 1.4281 grams of MDB and 1.5415 grams of propionic anhydride were placed in a 25 mL two-necked round-bottom flask and stirred to obtain a homogeneous solution. Then, 0.630 grams of catalyst (Nafion 13% w / w relative to silica, corresponding to a molar ratio of 0.007 between the active acid site and MDB) prepared as described in Example 29, with a particle size in the range of 40 μm to 100 μm, was inserted into the liquid mixture, and two condensers were attached to the flask. The reaction mixture was then placed in a preheated oil bath at 80 °C and reacted for 1 hour under magnetic stirring (500 rpm). After the reaction, the mixture was rapidly cooled in an ice bath, and the reaction mixture was recovered in 50 mL of acetone HPLC grade. 0.8 mL of the mixture was diluted in 10 mL of acetone HPLC grade, and 20 μL of octane was used as an internal standard for gas chromatography quantification. Analysis of the product at the end of the reaction was performed by GC equipped with an HP-5 (Agilent) capillary column (the temperature gradient used consisted of heating to 280°C at a rate of 10°C / min after 6 minutes at 35°C) and a flame ionization detector (FID). The results were as follows: 49% MDB conversion rate, 85% propionic anhydride conversion, 41% 3,4-methylenedioxypropiophenone yield and 85% selectivity, and 6% by-product yield.

Claims

1. A method for preparing 1-(1,3-benzodioxol-5-yl)-1-propanone, comprising the step of reacting 3,4-methylenedioxybenzene with propionic anhydride in the presence of a bulk or supported catalyst, wherein the catalyst is selected from the group consisting of sulfonated crosslinked polystyrene-divinylbenzene resin, sulfonated crosslinked polystyrene-divinylbenzene resin partially replaced with iron, zinc or gallium, perfluorinated sulfonate resin, and perfluorinated sulfonate resin partially replaced with iron, zinc or gallium, and the catalyst has an average particle size of 1 μm to 300 μm as measured by DLS (dynamic light scattering) or particle size measurement.

2. The method according to claim 1, wherein the catalyst has an average particle size of 1 μm to 180 μm as measured by DLS (dynamic light scattering) or particle size analyzer.

3. The method according to claim 1, wherein the catalyst has an average particle size of 1 μm to 100 μm as measured by DLS (dynamic light scattering) or a particle size analyzer.

4. The bulk or supported catalyst is a sulfonated crosslinked polystyrene-divinylbenzene resin used as a bulk or supported on silica, wherein the sulfonated crosslinked polystyrene-divinylbenzene resin contains 2 to 6 groups of SO per gram of material. ３ The method according to any one of claims 1 to 3, characterized by an acid loading amount expressed as mmol of H.

5. Base -SO per gram of material ３ The method according to any one of claims 1 to 4, wherein the acid load, expressed as mmol of H, is in the range of 2.5 to 5.

5.

6. Base -SO per gram of material ３ The method according to any one of claims 1 to 5, wherein the acid load expressed as mmol of H is 5.

7. The method according to any one of claims 1 to 3, wherein the bulk or supported catalyst is a perfluorinated sulfonic acid resin used as a bulk or supported on silica, and the perfluorinated sulfonic acid resin is characterized by an acid load of 0.2 to 2.

8. Base -SO per gram of material ３ The method according to claim 7, wherein the acid loading amount, expressed as mmol of H, is in the range of 0.7 to 1.

6.

9. Base -SO per gram of material ３ The method according to claim 8, wherein the acid loading amount, expressed as mmol of H, is 1.

2.

10. The method according to claim 1, wherein the bulk or supported catalyst is a sulfonated crosslinked polystyrene-divinylbenzene resin or a perfluorinated sulfonic acid resin partially replaced with iron, zinc, or gallium, and the partial replacement is a percentage of 5 to 80% of hydrogen atoms replaced with metal ions selected from Fe, Zn, and Ga.

11. The method according to claim 10, wherein the exchange percentage is 10 to 50%.

12. The method according to claim 11, wherein the exchange percentage is 30%.

13. The method according to any one of claims 1 to 12, wherein the catalyst is supported on an inorganic oxide.

14. The method according to claim 13, wherein the inorganic oxide is selected from zirconia, alumina, titania, and silica.

15. The method according to claim 14, wherein the inorganic oxide is selected from silica.

16. The method according to any one of claims 13 to 15, wherein the catalyst is supported on the inorganic oxide in an amount of 1 to 60 weight percent (%) relative to the total weight of the supported catalyst.

17. The method according to claim 16, wherein the catalyst is supported on the inorganic oxide in an amount of 5 to 30 weight percent (%) relative to the total weight of the supported catalyst.

18. The method according to claim 17, wherein the catalyst is supported on the inorganic oxide in an amount of 10 to 15 weight percent (%) relative to the total weight of the supported catalyst.

19. The method according to any one of claims 1 to 3, 7 to 9, or 10 to 16, wherein the step of reacting 3,4-methylenedioxybenzene with propionic anhydride is carried out in a temperature range of 50 to 200°C.

20. The method according to claim 19, wherein the temperature is in the range of 60 to 150°C.

21. The method according to claim 20, wherein the temperature is 80°C.

22. The method according to any one of claims 19 to 21, wherein the reaction time is 5 to 240 minutes.

23. The method according to claim 22, wherein the reaction time is 5 to 120 minutes.

24. The method according to claim 23, wherein the reaction time is 60 minutes.

25. The method according to any one of claims 1 to 6, 10 to 18, wherein the step of reacting 3,4-methylenedioxybenzene with propionic anhydride is carried out in a temperature range of 50 to 150°C.

26. The method according to claim 25, wherein the temperature is in the range of 60 to 130°C.

27. The method according to claim 26, wherein the temperature is 80°C or 130°C.

28. The method according to any one of claims 25 to 27, wherein the reaction time is 5 to 240 minutes.

29. The method according to claim 28, wherein the reaction time is 5 to 120 minutes.

30. The method according to claim 29, wherein the reaction time is 60 minutes.

31. The method according to any one of claims 1 to 3, 7 to 9, or 10 to 22, wherein the amount of the catalyst, expressed as the ratio of H+ or active sites per mole of limiting reagent, is 0.0001 to 1.

32. The method according to claim 31, wherein the amount of the catalyst is 0.001 to 0.

04.

33. The method according to claim 32, wherein the amount of the catalyst is 0.

007.

34. The method according to any one of claims 1 to 6, 10 to 18, or 25 to 30, wherein the amount of the catalyst, expressed as the ratio of H+ or active sites per mole of limiting reagent, is 0.002 to 1.

35. The method according to claim 34, wherein the amount of the catalyst is 0.01 to 0.

08.

36. The method according to claim 35, wherein the amount of the catalyst is 0.

03.

37. The method according to any one of claims 1 to 36, wherein the step of reacting 3,4-methylenedioxybenzene with propionic anhydride is carried out in a molar ratio of 3,4-methylenedioxybenzene to propionic anhydride in the range of 2 to 1:1 to 2.

38. The method according to claim 37, wherein the molar ratio is a stoichiometric ratio of 1:

1.

39. The method according to any one of claims 1 to 38, wherein the catalyst is recovered, regenerated, and recycled.

40. The method according to claim 39, wherein the catalyst is recovered by filtration from the suspension of the reaction medium and nitric acid aqueous solution.

41. The method according to claim 40, wherein the concentration of the diluted aqueous solution of nitric acid is in the range of 2% by weight to 60% by weight.

42. The method according to claim 41, wherein the concentration of the diluted aqueous solution of nitric acid is in the range of 10% by weight to 40% by weight.

43. The method according to claim 42, wherein the concentration of the diluted aqueous solution of nitric acid is 20% by weight.

44. The method according to claim 39, wherein the catalyst is recovered by filtration from the suspension of the reaction medium and hydrochloric acid in a diluted aqueous solution.

45. The method according to claim 44, wherein the concentration of the diluted aqueous solution of hydrochloric acid is in the range of 2% by weight to 30% by weight.

46. The method according to claim 45, wherein the concentration of the diluted aqueous solution of hydrochloric acid is 20% by weight.

47. The method according to any one of claims 39 to 46, wherein the recovery of the catalyst is carried out at a temperature in the range of room temperature to reflux, over a period of time in the range of several minutes to four hours.

48. The method according to claim 47, wherein the aforementioned time is 1 hour.

49. The recovery, regeneration, and recycling of the catalyst are performed by H ２ O ２ The method according to claim 39, which is carried out using

50. The method according to any one of claims 1 to 49, wherein the catalyst has an average particle size of 40 μm to 100 μm.

51. The method according to any one of claims 1 to 50, wherein the method is a continuous method.

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