Method for oxidizing lipophilic ethylenically unsaturated organic compounds

Abstract

The present invention relates to a method for oxidizing a lipophilic ethylenically unsaturated organic prising a homogeneous catalyst system and a solvent capable of forming a thermomorphic reaction system. The invention further relates to a method for synthesizing a lactam and to a mixture for use in such methods.

Description

[0001] 202300279 Foreign Filings

[0002] 1

[0003] METHOD FOR OXIDIZING LIPOPHILIC ETHYLENICALLY UNSATURATED ORGANIC COMPOUNDS

[0004] The present invention relates to a method for oxidizing a lipophilic ethy lenically unsaturated organic compound in a reaction mixture comprising a homogeneous catalyst system and a solvent capable of forming a thermomorphic reaction system. The invention further relates to a method for synthesizing a lactam and to a mixture for use in such methods.

[0005] Homogeneous catalysis using transition metal catalysts plays an essential role in a variety of oxidation reactions of unsaturated organic compounds. This type of reaction is commonly carried out in a biphasic system and typically requires the use of a phase transfer reagent, such as a ternary or quaternary ammonium compound. The phase transfer reagents essentially fulfil two main functions. On the one hand, they enable emulsification of the organic nonpolar and aqueous polar phases to induce sufficient transfer of the different substances, and on the other hand, they act as extractants to transfer the catalyst components into the organic phase to enable the oxidation reaction.

[0006] For instance, C. Venturello et al. describe a process for the epoxidation of olefins, such as 1 -octene and cyclohexene, using hydrogen peroxide in the presence of a polytungstophosphate catalyst and a tetraalkylammonium phase transfer catalyst, such as methyltrioctylammonium chloride, in a biphasic solvent mixture (J. Org. Chem. 1983, 48, 3831 -3833). Technical applications of such oxidation reactions include the synthesis of 1 ,2-propanediol as described in WO 2023 / 152083 A1 and methods for the epoxidation of cyclododecene (CDEN) with hydrogen peroxide as oxidant in a biphasic reaction mixture as described, for instance, in EP 1 411 050 B1 , EP 2 980 069 A1 and WO 2021 / 085978 A. Recently, the recycling and reactivation of homogeneous catalyst systems used in such processes has become increasingly important, especially in large-scale industrial and continuous processes. Special membrane techniques and reactivation methods are, for example, described in EP 2 946 831 A2 and WO 2018 / 002114 A1.

[0007] However, the use of phase transfer reagents in such methods can still have some drawbacks. For instance, inactive catalyst species, which might be formed over time, can be extracted by the phase transfer reagent from the aqueous phase into the organic phase. These species may then accumulate in the organic phase and extensive methods are required to reactivate or separate these species. Moreover, a loss of catalyst can occur if the catalyst system is not completely transferred into the organic phase. Furthermore, the use of phase transfer reagents can be associated with the formation of solid precipitates, which may clog parts of the reactors. Finally, some phase transfer reagents which are typically used are classified as CMR (carcinogenic, mutagenic or toxic for reproduction) substances and a substitution is highly desired.

[0008] Hence, there remains a need for alternative processes that allow homogeneous catalysis of oxidation reactions while avoiding the use of phase transfer reagents. 202300279 Foreign Filings

[0009] 2

[0010] It has now surprisingly been found that the use of a phase transfer reagent in oxidation reactions of lipophilic ethylenically unsaturated organic compounds can be avoided when a solvent capable of forming a thermomorphic reaction system (TMS) is used.

[0011] This method provides the benefit that the drawbacks of the typically used phase transfer reagents can be completely avoided. Surprisingly, it has also been found that, after the reaction occurred, the catalyst system is present almost completely in the aqueous phase, eliminating the need for further steps of separating it from the product-containing organic phase. The use of a reaction mixture comprising a solvent capable of forming a TMS can allow the combination of the advantages of monophasic reaction systems, which are typically associated with high productivity, and of liquid multiphase systems, which are typically associated with efficient catalyst recovery.

[0012] Accordingly, the present invention relates to a method for the oxidation of a lipophilic ethylenically unsaturated organic compound in a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state, a solvent capable of forming a thermomorphic reaction system and water, comprising the steps of

[0013] (i) providing a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, the homogeneous catalyst system, the peroxide, the solvent capable of forming a thermomorphic reaction system and water;

[0014] (ii) oxidizing the lipophilic ethylenically unsaturated organic compound in the reaction mixture;

[0015] (iii) forming a biphasic reaction mixture comprising an aqueous phase in which the catalyst system is concentrated by reducing the temperature and / or by distilling off at least a part of the solvent capable of forming a thermomorphic reaction system from the reaction mixture and an organic phase containing the oxidized ethylenically unsaturated organic compound; and

[0016] (iv) separating the aqueous phase containing the catalyst system from the organic phase containing the oxidized ethylenically unsaturated organic compound; wherein the reaction mixture comprises less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, based on the total weight of the reaction mixture.

[0017] Moreover, the present invention relates to a method for synthesizing a lactam, comprising: epoxidizing a cyclic lipophilic ethylenically unsaturated organic compound to an epoxide; rearranging the epoxide to a ketone; converting the ketone to an oxime; and rearranging the oxime to give the lactam; wherein the cyclic lipophilic unsaturated organic compound is epoxidized by the method for oxidation described herein.

[0018] Furthermore, the present invention relates to a mixture comprising tungsten in an amount of more than 1000 ppm, phosphorous in an amount of more than 10 ppm, hydrogen peroxide in an amount of from 0.05 to 5.0 wt.-%, a lipophilic ethylenically unsaturated organic compound and an oxidation product of the lipophilic ethylenically unsaturated organic compound in a combined amount of at least 5 wt.-% and not more than 80 wt.-%, a tertiary alcohol in an amount of at least 10 wt.-% and less than 95 wt.-%, and less 202300279 Foreign Filings

[0019] 3 than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, wherein wt.-% is based on the total weight of the mixture.

[0020] As used herein, the term "comprising" and variations thereof are used synonymously with the terms "including", "containing" and variations thereof and are understood to be open and non-limiting terms which do not exclude the presence of additional undescribed or unrecited elements, compounds, ingredients or process steps. As used herein, the term "consisting of is understood to exclude the presence of unspecified elements, compounds, ingredients or process steps. When the non-limiting terms “comprising”, “including” or “containing” are used in the present specification, the case of ’’consisting of is included therein. For example, a process described as “comprising” or “including” certain steps can consist of the explicitly recited steps or can further comprise one or more unrecited steps. The same applies, for example, to compositions and their corresponding explicitly described or non-recited ingredients.

[0021] In this application, the indefinite article "a" means one or more of what it denotes.

[0022] As stated above, the present invention relates to a method for the oxidation of a lipophilic ethy lenically unsaturated organic compound in a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state, a solvent capable of forming a thermomorphic reaction system and water and less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, based on the total weight of the reaction mixture.

[0023] According to the present invention, the oxidation of a lipophilic ethylenically unsaturated organic compound can be an epoxidation of a lipophilic ethylenically unsaturated organic compound.

[0024] The reaction mixture of the oxidation comprises a lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state, a solvent capable of forming a thermomorphic reaction system and water.

[0025] In the oxidation according to the present invention a peroxide is used as an oxidant. Suitable peroxides are known to those skilled in the art and include 3-chloroperoxybenzoic acid, peroxybenzoic acid, peroxyacetic acid, peroxybenzimidic acid, tert-butylhydroperoxide, dimethlydioxirane, potassium hydrogen peroxo mo nosulfate and hydrogen peroxide, wherein hydrogen peroxide is the preferred peroxide.

[0026] As used herein, the term “lipophilic ethylenically unsaturated organic compound” refers to an organic compound having at least one carbon-carbon double bond and / or at least one carbon-carbon triple bond, preferably at least on carbon-carbon double bond, and that does not dissolve in water and has the ability to dissolve in non-polar substances such as lipids. Preference is given to lipophilic ethylenically 202300279 Foreign Filings

[0027] 4 unsaturated organic compounds having a solubility in water at 20 °C of no more than 1 wt.-%, preferably of no more than 0.5 wt.-%. A solubility in water at 20 °C of 1 wt.-%, as used herein, means that at a temperature of 20 °C no more than 10 g of the respective compound dissolves in 1000 g of distilled water. The lipophilic ethylenically unsaturated organic compound preferably comprises a cyclic or acyclic olefin or a combination thereof, preferably a cyclic or acyclic olefin having 6 to 20 carbon atoms, more preferably a cyclic olefin. Particularly preferred are cyclic unsaturated C12 compounds, especially cyclododecene (CDEN).

[0028] As used herein the term "oxidized ethylenically unsaturated compound" refers to any product resulting from oxidizing at least one carbon-carbon double of the ethylenically unsaturated organic compound, such as, but not limited to the corresponding epoxide. The oxidized ethylenically unsaturated compound preferably is 1 ,2-epoxycyclododecane (CDAN-epoxide).

[0029] As used herein, the term "homogeneous catalyst system" is to be understood in the way it is generally understood by a skilled person in the field of organic synthesis, namely as a catalyst system used in homogeneous catalysis, wherein the catalyst is in the same phase as the reactants such as in case of a soluble catalyst in a solution. The homogeneous catalyst system catalyzes the oxidation of the lipophilic ethylenically unsaturated organic compound in the reaction mixture. The homogeneous catalyst system comprises at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state.

[0030] As used herein, the term “transition metal of Group IVb” refers to an element that is in Group IVb of the CAS version of the Periodic Table of the Elements as is shown, for example, in the Handbook of Chemistry and Physics, 63rd edition (1983), corresponding to Group 4 in the actual IUPAC numbering. Likewise, the terms “transition metal of Group Vb” and “transition metal of Group Vlb” refer to an element that is in Group Vb and Vlb, respectively, of the CAS version of the Periodic Table of the Elements as is shown, for example, in the Handbook of Chemistry and Physics, 63rd edition (1983), corresponding to Group 5 and 6, respectively, in the actual IUPAC numbering.

[0031] The at least one derivative of the transition metal of Group IVb, Vb and Vlb preferably may be selected from a derivative of tungsten (oxidation state 6), molybdenum (oxidation state 6) and vanadium (oxidation state 5).

[0032] Suitable derivatives include, for example, oxides, mixed oxides, oxygen-containing acids, salts of oxygencontaining acids, carbonyl derivatives, sulfides, chlorides, oxychlorides and alkanoates of tungsten, molybdenum and / or vanadium.

[0033] Preference is given to derivatives selected from salts of tungstic acid (H2WO4) or molybdic acid (H2MOO4), or homo- or heteropolyoxometalates formed therefrom. Special preference is given to derivatives selected from alkali or alkaline earth metal salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, in particular to Na2WO4 or a homo- or heteropolyoxometalate formed therefrom. 202300279 Foreign Filings

[0034] 5

[0035] A polyoxometalate is a polyatomic ion, usually an anion, comprising three or more transition metal oxyanions linked together by shared oxygen atoms to form closed 3-dimensional frameworks. Homopolyoxometalates are composed of only one kind of metal and oxygen, while heteropolyoxometalates are composed of one or more metals, oxygen and eventually a main group oxyanion, such as a phosphate or a silicate.

[0036] These derivatives can be formed or converted into the catalytically active species in situ. For instance, the catalyst system can further comprise phosphoric acid, a salt of phosphoric acid, a bisulfate, a sulfate or a combination thereof. For example, sodium tungstate can be used in combination with phosphoric acid to form a catalytically active polyoxometalate in situ. Phosphoric acid or salts thereof can, for instance, be used as a stabilizer for hydrogen peroxide and thus, if hydrogen peroxide is used as the oxidant, be added to the reaction mixture in this form in combination with the hydrogen peroxide. A suitable bisulfate used in the present methods is, for instance, sodium bisulfate. A suitable sulfate used in the present methods is, for instance, sodium sulfate.

[0037] As used herein, a “solvent capable of forming a thermomorphic reaction system” refers to a substance preferably being liquid at ambient temperature, being able to dissolve or disperse another substance and being able to form a thermomorphic reaction system (TMS) in combination with at least one other liquid component, such as at least one other solvent, such as with two other liquid components / solvents.

[0038] Unless stated otherwise, "ambient temperature" or "room temperature" as used herein refers to a temperature of 23 °C.

[0039] The term “thermomorphic reaction system" as used herein, refers to a reaction system comprising a mixture of at least two liquid components, such as solvents, of different polarity having a temperature dependent miscibility gap. In other words, the at least two liquid components are immiscible and form two liquid phases (biphasic mixture) at a first temperature and form a single homogeneous reaction phase (monophasic mixture) at a second temperature, wherein the first temperature preferably is lower than the second temperature. This may allow a reversible switch from a biphasic reaction mixture to a monophasic (homogeneous) reaction mixture, or vice versa, depending on the temperature of the reaction system.

[0040] A "thermomorphic reaction system" according to the present invention preferably refers to a TMS comprising at least three different liquid components, which might be solvents, i.e., one polar liquid component, one nonpolar liquid component and the solvent capable of forming a thermomorphic reaction system. The polar liquid component may be water. The nonpolar liquid component may be a nonpolar organic solvent and / or the lipophilic ethylenically unsaturated organic compound. For instance, if CDEN is used as the lipophilic ethylenically unsaturated organic compound, it represents the nonpolar liquid component, while water represents the polar liquid component. The polar liquid component, the non-polar liquid component and the solvent capable of forming a thermomorphic reaction system can, for example, be combined in a weight ratio of from 5-20 wt.-% to 5-30 wt.-% to 50-90 wt.-%, based on the total 202300279 Foreign Filings

[0041] 6 combined weight of the three liquid components, preferably of from 5-15 wt.-% to 5-25 wt.-% to 60-90 wt.- %, based on the total combined weight of the three liquid components. The ratio of the three liquids to each other depends on the actual system and other ranges might be possible.

[0042] The solvent capable of forming a thermomorphic reaction system with water and the lipophilic unsaturated organic compound preferably comprises a tertiary alcohol, more preferably a tertiary alcohol having a boiling temperature lower than that of the oxidized organic compound. Special preference is given to tert-butanol, tert-amyl alcohol or a combination thereof.

[0043] If a tertiary alcohol is used as the solvent capable of forming a thermomorphic reaction system, the solvent itself may provide further benefits, since it may transfer the oxygen of the peroxide to the unsaturated organic compound which is to be oxidized without being oxidized itself.

[0044] As stated above, the reaction mixture comprises less than 0.1 wt.-% of a tertiary or quaternary ammonium compound, based on the total weight of the reaction mixture, preferably less than 0.05 wt.-%, more preferably less than 0.01 wt.-%. The reaction mixture most preferably is completely free of a tertiary or quaternary ammonium compound, i.e., the amount of tertiary or quaternary ammonium compound is below the detection limit of these substances, in particular, no tertiary or quaternary ammonium compound is intentionally added to the reaction mixture.

[0045] In the first step (step (i)) of the present method for the oxidation of a lipophilic ethylenically unsaturated organic compound a reaction mixture is provided comprising the lipophilic ethylenically unsaturated organic compound, the homogeneous catalyst system, the peroxide, the solvent capable of forming a thermomorphic reaction system and water.

[0046] The reaction mixture provided in step (i) may comprise the lipophilic ethylenically unsaturated organic compound in an amount of from 5 to 80 wt.-%, preferably of from 5 to 60 wt.-%, more preferably of from 5 to 30 wt.-%, even more preferably of from 5 to 25 wt.-%, based on the total weight of the reaction mixture.

[0047] The reaction mixture provided in step (i) may comprise the homogeneous catalyst system in such an amount, that the transition metal of Group IVb, Vb and Vlb is present in an amount of from 100 to 5000 ppm, preferably of from 500 to 4000 ppm, based on the total weight of the reaction mixture.

[0048] The reaction mixture provided in step (i) may comprise the peroxide in an amount of from 0.05 to 5.0 wt.- %, preferably of from 0.1 to 4.0 wt.-%, more preferably of from 1 .5 to 3.5 wt.-%, based on the total weight of the reaction mixture.

[0049] The reaction mixture provided in step (i) may comprise the solvent capable of forming a thermomorphic reaction system in an amount of from 10 to 95 wt.-%, preferably of from 25 to 90 wt.-%, more preferably of from 50 to 90 wt.-%, even more preferably of from 60 to 90 wt.-%, based on the total weight of the reaction mixture. 202300279 Foreign Filings

[0050] 7

[0051] The reaction mixture may be provided in step (i) by providing a first mixture of the lipophilic ethylenically unsaturated organic compound and the solvent capable of forming a thermomorphic reaction system and a second mixture of the homogeneous catalyst system, peroxide and water, and combining the first and second mixture. Herein the first and second mixture are preferably combined at elevated temperature, i.e., a temperature above room temperature, such as a temperature of from 60 to 120 °C, preferably of from 80 to 110 °C and more preferably of from 90 to 105 °C. Herein the temperature may be raised either before or after all components are added to the reaction mixture.

[0052] The reaction mixture provided in step (i) may form a monophasic reaction mixture under certain conditions, in particular at elevated temperatures, such as at a temperature of from 60 to 120 °C, preferably of from 80 to 110 °C and more preferably of from 90 to 105 °C. The term "monophasic reaction mixture" as used herein refers to a reaction mixture forming a liquid homogeneous phase. In this case the reaction mixture forms a thermomorphic reaction system with the solvent capable of forming a TMS and a single homogeneous reaction phase is formed.

[0053] Alternatively, the reaction mixture formed in step (i) of the present method may not be in form of a completely monophasic reaction mixture, but a partial phase separation may occur, for instance, when the reaction is carried out close to but below the upper critical solution temperature (UCST) at which the components of the reaction mixture are miscible to form a monophasic solution in all portions, if mixing of these partially separated phases occurs to such an extent that the positive effects described above can be achieved.

[0054] In the second step (step (ii)) of the present method for the oxidation of a lipophilic ethylenically unsaturated organic compound, the lipophilic ethylenically unsaturated organic compound is oxidized in the reaction mixture. Depending on the temperature at which the oxidation is carried out, the reaction mixture in the second step may be either a monophasic reaction mixture or a reaction mixture having an at least partial phase separation. The oxidation of step (i) is preferably carried out at elevated temperature, such as a temperature of from 60 to 120 °C, preferably of from 80 to 110 °C and more preferably of from 90 to 105 °C.

[0055] In the third step (step (iii)) of the present method for the oxidation of a lipophilic ethylenically unsaturated organic compound, a biphasic reaction mixture is formed comprising an aqueous phase in which the catalyst system is concentrated and an organic phase containing the oxidized ethylenically unsaturated organic compound. The biphasic mixture can either be formed by reducing the temperature of the reaction mixture or by distilling off at least a part of the solvent capable of forming a thermomorphic reaction system from the reaction mixture or by a combination of both. The distillation may be performed at a temperature which corresponds to the boiling point of the solvent capable of forming a thermomorphic reaction system. 202300279 Foreign Filings

[0056] 8

[0057] The term "biphasic reaction mixture" as used herein refers to a mixture comprising two liquid phases being immiscible at a given temperature, namely an aqueous phase and an organic phase.

[0058] Using this concept of a thermomorphic reaction system, depending on the conditions, in particular the temperature, it is possible to have all reactants, adjuvants and catalysts in one liquid phase (monophasic reaction mixture), while at different conditions (i.e., separation conditions) products and catalysts are contained in two different liquid phases (biphasic reaction mixture). Thus, the advantages typically associated with monophasic reaction systems, i.e., a high productivity, can be combined with those typically associated with liquid multiphase systems, i.e., efficient catalyst recovery. Hence, the limitation of material transfer between different phases in a two-phase system is reduced or even eliminated and the solvent capable of forming a thermomorphic reaction mixture thus indirectly carries out material transfer between the two phases and replaces a typical phase transfer reagent.

[0059] If the biphasic mixture formed in step (iii) is formed by reducing the temperature of the reaction mixture, the reaction mixture represents a thermomorphic reaction system as described above and with decreasing temperature the miscibility gap of the liquid components is exploited. The temperature may be reduced to a temperature of less than 60 °C, e.g., of from 40 to less than 60 °C.

[0060] In the fourth step (step (iv)) of the present method for the oxidation of a lipophilic ethylenically unsaturated organic compound, the aqueous phase formed in step (iii) containing the catalyst system is separated from the organic phase containing the oxidized ethylenically unsaturated organic compound.

[0061] In case the biphasic reaction mixture in step (iii) is formed by reducing the temperature, the method may further comprise a step of (v) separating the solvent capable of forming a thermomorphic reaction system from the oxidized lipophilic ethylenically unsaturated organic compound. The solvent capable of forming a thermomorphic reaction system may preferably be separated in step (v) by distillation.

[0062] The method for oxidation according to the present invention may further comprise a step (vi) of further concentrating the catalyst system in the aqueous phase separated in step (iv). The catalyst system may preferably further be concentrated in step (vi) by distillation and / or membrane filtration. The further concentration in step (vi) by distillation may be performed by distilling off water from the aqueous phase. The further concentration in step (vi) can be carried out until a desired concentration of catalyst in the aqueous phase is reached. Step (vi) may be carried out to recover the homogeneous catalyst system.

[0063] Suitable membrane systems include but are not limited to comprise a membrane material selected from the following: polyamides, aromatic polyamides, polysulphones, polyethersulphones, hydrophobized polyethersulphones, sulphonated polyethersulphones, cellulose acetate, polypiperazine and polyvinylidene fluoride. The membrane can be a part of a continuous membrane system having multiple membrane modules. 202300279 Foreign Filings

[0064] 9

[0065] The method for the oxidation according to the present invention may be carried out as a batch process or as a continuous process, wherein a continuous process is preferred. The continuous process may be carried out in one stirred tank reactor or in a series of stirred tank reactors. This series of stirred tank reactors preferably comprises at least two stirred tank reactors, more preferably three to five stirred tank reactors. When using a series of stirred tank reactors, the peroxide can be dosed into all of the reactors or only into some of the reactors.

[0066] According to the method for oxidation of the present invention, the catalyst system concentrated in step (vi) and / or the solvent capable of forming a thermomorphic reaction system separated in step (v) or distilled off in step (iii) may be recycled to provide a reaction mixture as defined in step (i). The recycling may be performed by adding peroxide to the aqueous phase comprising the catalyst system concentrated in step (vi), adding the solvent separated in step (v) or distilled off in step (iii) to a reactor comprising fresh lipophilic ethy lenically unsaturated organic compound and adding the aqueous solution comprising the peroxide and the catalyst system into the reactor at elevated temperature.

[0067] The present invention further relates to a method for synthesizing a lactam, comprising: epoxidizing a cyclic lipophilic ethylenically unsaturated organic compound to an epoxide, rearranging the epoxide to a ketone, converting the ketone to an oxime, and rearranging the oxime to the lactam, wherein the cyclic ethylenically unsaturated organic compound is epoxidized according to the method for the oxidation of a lipophilic ethylenically unsaturated organic compound described herein.

[0068] The method for synthesizing a lactam is particularly suitable for synthesizing laurolactam. The cyclic ethylenically unsaturated compound preferably may comprise 6 to 20 carbon atoms, more preferably 12 carbon atoms and most preferably is CDEN.

[0069] In the first step of the method for synthesizing a lactam, the organic compound is oxidized to the corresponding epoxide. The epoxidation is carried out according to the method described herein above. The epoxidized compound is subsequently rearranged, for instance in the presence of a catalyst comprising a noble metal and a metal oxide, to the corresponding ketone. During said rearrangement or subsequent thereto, hydrogen can be added, so that the corresponding alcohol is formed. If the ketone is present in a mixture with the alcohol derivative, a dehydrogenation of the alcohol to the ketone can take place. The ketone is then converted to an oxime and finally the lactam is obtained by subsequent Beckmann rearrangement using e.g., sulfuric acid or cyanuric chloride. The rearrangement of the epoxide to the ketone and the subsequent steps are disclosed, for instance, in EP 2 772478 A1 . The resulting lactam can be subjected to further processing by polycondensation to give polyamides. A method for synthesizing laurolactam from CDEN via 1 ,2-epoxycyclododecane (CDAN epoxide) as an intermediate is particularly preferred. The obtained laurolactam can be polymerized to nylon 12 afterwards.

[0070] The present invention further relates to a mixture comprising tungsten in an amount of more than 1000 ppm, phosphorous in an amount of more than 10 ppm, 202300279 Foreign Filings

[0071] 10 hydrogen peroxide in an amount 0.05 to 5.0 wt.-%, a lipophilic ethylenically unsaturated organic compound and an oxidation product of the lipophilic ethylenically unsaturated organic compound in a combined amount of at least 5 wt.-% and not more than 80 wt.-%, a tertiary alcohol in an amount of at least 10 wt.-% and less than 95 wt.-%, and less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, wherein wt.-% is based on the total weight of the mixture. The lipophilic ethylenically unsaturated organic compound preferably is CDEN and the oxidation product preferably is CDAN-epoxide.

[0072] The mixture according to the present invention described above can be used as the reaction mixture in the method for oxidizing a lipophilic ethylenically unsaturated organic compound and is particularly suitable for use in a continuous process.

[0073] The amount of the transition metal, for instance tungsten, and the amount of phosphorous in the mixture according to the present invention or in any organic or aqueous phase obtained or used in the methods according to the present invention can be determined by X-ray fluorescence spectroscopy using, for instance, a SPECTRO XEPOS spectrometer of type 16004851 from SPECTRO Analytical Instruments GmbH (Kleve, Germany). For doing so, a sample is centrifuged at room temperature (23 °C) for 1 min at 4000 rpm for complete phase separation. The phases are separated by pipetting, and 5 g of each phase is transferred into a single usage cuvette having a diameter of 32 mm from SPECTRO Analytical Instruments GmbH (Kleve, Germany). The concentration is determined via X-ray fluorescence analysis using a SPECTRO XEPOS spectrometer, type 16004851 from SPECTRO Analytical Instruments GmbH (Kleve, Germany). The sample chamber is inertized with helium. The amount of the transition metal is determined using a method calibrated with the pure substances, for instance sodium tungstate and phosphoric acid (75%).

[0074] The amounts of the lipophilic ethylenically unsaturated organic compound, the oxidation product of the lipophilic ethylenically unsaturated organic compound, for instance an epoxide, and the tertiary alcohol can for example be determined by gas chromatography with a flame ionization detector (GC-FID) using, for instance, a GC-2014 gas chromatograph from Shimadzu Deutschland GmbH (Duisburg, Germany). The determination can be carried out as follows: a sample of the biphasic mixture is centrifuged at room temperature (23 °C) for 1 min at 4000 rpm for obtaining a complete phase separation. 100 mg of the organic phase is weighed into a GC vial and diluted with standard solution by a factor of 10. The 10 wt.-% standard solution comprises 1 wt.-% of tetradecane and is further filled up with acetone. The measurement is performed using a Shimadzu GC-2014 gas chromatograph with a Supelcowax-10 column (length of 60 m, diameter of 0.32 mm and film thickness of 0.25 pm) with a flame ionization detector and a SPL-10 Split Injector. The sample is injected at 150 °C with a split of 1 :10. The initial column temperature is 180 °C, which is hold for 10 min, then increased with a temperature ramp of 5 K / min to 200 °C and kept at this temperature for 35 min. The products are quantified by comparing the area under the curve of the products with the area of tetradecane as internal standard in correlation with the initial weight and a response factor, which is determined beforehand by recovery of the pure substances in a concentration series. 202300279 Foreign Filings

[0075] 11

[0076] The following clauses summarize some aspects of the present invention:

[0077] In a first aspect the present invention relates to a method for the oxidation of a lipophilic ethy lenically unsaturated organic compound in a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state, a solvent capable of forming a thermomorphic reaction system and water, comprising the steps of (i) providing a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, the homogeneous catalyst system, the peroxide, the solvent capable of forming a thermomorphic reaction system and water; (ii) oxidizing the lipophilic ethylenically unsaturated organic compound in the reaction mixture; (iii) forming a biphasic reaction mixture comprising an aqueous phase in which the catalyst system is concentrated by reducing the temperature and / or by distilling off at least a part of the solvent capable of forming a thermomorphic reaction system from the reaction mixture and an organic phase containing the oxidized ethylenically unsaturated organic compound; and (iv) separating the aqueous phase containing the catalyst system from the organic phase containing the oxidized ethylenically unsaturated organic compound; wherein the reaction mixture comprises less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, based on the total weight of the reaction mixture.

[0078] In a second aspect the present invention relates to the method of the first aspect, wherein, when the biphasic reaction mixture in step (iii) is formed by reducing the temperature, the method further comprises a step (v) of separating the solvent capable of forming a thermomorphic reaction system from the oxidized lipophilic ethylenically unsaturated organic compound.

[0079] In a third aspect the present invention relates to the method of the second aspect, wherein in step (v) the solvent capable of forming a thermomorphic reaction system is separated by distillation.

[0080] In a fourth aspect the present invention relates to the method of any one of the preceding aspects, wherein the method further comprises a step (vi) of further concentrating the catalyst system in the aqueous phase separated in step (iv).

[0081] In a fifth aspect the present invention relates to the method of the fourth aspect, wherein in step (vi) the catalyst system is further concentrated by distillation and / or membrane filtration.

[0082] In a sixth aspect the present invention relates to the method of any one of the preceding aspects, wherein the method is carried out as a continuous process.

[0083] In a seventh aspect the present invention relates to the method of any one of the preceding aspects, wherein the catalyst system concentrated in step (vi) is recycled to provide the reaction mixture in step (i). 202300279 Foreign Filings

[0084] 12

[0085] In an eighth aspect the present invention relates to the method of any one of the preceding aspects, wherein the solvent capable of forming a thermomorphic reaction system separated in step (v) or distilled off in step (iii) is recycled to provide the reaction mixture in step (i).

[0086] In a ninth aspect the present invention relates to the method of any one of the preceding aspects, wherein the reaction mixture provided in step (i) forms a monophasic reaction mixture.

[0087] In a tenth aspect the present invention relates to the method of the ninth aspect, wherein the monophasic reaction mixture is formed by elevating the temperature of the reaction mixture.

[0088] In a twelfth aspect the present invention relates to the method of any one of the preceding aspects, wherein the lipophilic ethylenically unsaturated organic compound comprises a cyclic or acyclic olefin or a combination thereof, preferably a cyclic or acyclic olefin having 6 to 20 carbon atoms, more preferably a cyclic olefin, wherein the lipophilic ethylenically unsaturated organic compound most preferably is cyclododecene.

[0089] In a thirteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the at least one derivative of the transition metal of Group IVb, Vb and Vlb is selected from a derivative of tungsten, molybdenum and vanadium, wherein the derivative preferably is selected from salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, more preferably from alkali or alkaline earth metal salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, and most preferably is Na2WO4 or a homo- or heteropolyoxometalate formed therefrom.

[0090] In a fourteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the homogeneous catalyst system further comprises phosphoric acid, a salt of phosphoric acid, a bisulfate, a sulfate or a combination thereof.

[0091] In a fifteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the solvent capable of forming a thermomorphic reaction system comprises a tertiary alcohol, preferably a tertiary alcohol having a boiling temperature lower than that of the oxidized organic compound, more preferably tert-butanol, tert-amyl alcohol or a combination thereof.

[0092] In a sixteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the peroxide comprises hydrogen peroxide.

[0093] In a seventeenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the reaction mixture provided in step (i) comprises water, the lipophilic ethylenically unsaturated organic compound and the solvent capable of forming a thermomorphic reaction system in a weight ratio of from 5-20 wt.-% to 5-30 wt.-% to 50-90 wt.-%, based on the total combined weight of the three components, preferably of from 5-15 wt.-% to 5-25 wt.-% to 60-90 wt.-%, based on the total combined weight of the three components. 202300279 Foreign Filings

[0094] 13

[0095] In an eighteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the reaction mixture provided in step (i) comprises the lipophilic ethylenically unsaturated organic compound in an amount of from 5 to 80 wt.-%, preferably of from 5 to 60 wt.-%, more preferably of from 5 to 30 wt.-%, even more preferably of from 5 to 25 wt.-%, based on the total weight of the reaction mixture.

[0096] In a nineteenth aspect the present invention relates to the method of any one of the preceding aspects, wherein the reaction mixture provided in step (i) comprises the peroxide in an amount of from 0.05 to 5.0 wt.-%, preferably of from 0.1 to 4.0 wt.-%, more preferably of from 1 .5 to 3.5 wt.-%, based on the total weight of the reaction mixture.

[0097] In a twentieth aspect the present invention relates to the method of any one of the preceding aspects, wherein the reaction mixture provided in step (i) comprises the solvent capable of forming a thermomorphic reaction system in an amount of from 10 to 95 wt.-%, preferably of from 25 to 90 wt.-%, more preferably of from 50 to 90 wt.-%, even more preferably of from 60 to 90 wt.-%, based on the total weight of the reaction mixture.

[0098] In a twenty-first aspect the present invention relates to a method for synthesizing a lactam, comprising: epoxidizing a cyclic lipophilic ethylenically unsaturated compound to an epoxide; rearranging the epoxide to a ketone; converting the ketone to an oxime; and rearranging the oxime to lactam; wherein the cyclic lipophilic ethylenically unsaturated compound is epoxidized according to the method of any one of aspects 1 to 20.

[0099] In a twenty-second aspect the present invention relates to a mixture comprising tungsten in an amount of more than 1000 ppm, phosphorous in an amount of more than 10 ppm, hydrogen peroxide in an amount of from 0.05 to 5.0 wt.-%, a lipophilic ethylenically unsaturated organic compound and an oxidation product of the lipophilic ethylenically unsaturated organic compound in a combined amount of at least 5 wt.-% and not more than 80 wt.-%, a tertiary alcohol in an amount of at least 10 wt.-% and less than 95 wt.-%, and less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, wherein wt.-% is based on the total weight of the mixture.

[0100] In a twenty-third aspect the present invention relates to the mixture of the twenty-second aspect, comprising hydrogen peroxide in an amount of from 1 .5 to 3.5 wt.-%, the lipophilic ethylenically unsaturated organic compound and the oxidation product of the lipophilic ethylenically unsaturated organic compound in a combined amount of at least 50 wt.-% and not more than 30 wt.-%, and the tertiary alcohol in an amount of at least 60 wt.-% and less than 90 wt.-%, wherein wt.-% is based on the total weight of the mixture.

[0101] In a twenty-fourth aspect the present invention relates to the mixture of the twenty-second or twenty-third aspect, wherein the lipophilic ethylenically unsaturated organic compound comprises CDEN and the oxidation product comprises CDAN-epoxide. 202300279 Foreign Filings

[0102] 14

[0103] In a twenty-fifth aspect the present invention relates to the use of a tertiary alcohol to form a thermomorphic reaction system in a reaction mixture comprising a lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state and water.

[0104] In a twenty-sixth aspect the present invention relates to the use of the twenty-fifth aspect, wherein the lipophilic ethylenically unsaturated organic compound comprises a cyclic or acyclic olefin or a combination thereof, preferably a cyclic or acyclic olefin having 6 to 20 carbon atoms, more preferably a cyclic olefin, wherein the lipophilic ethylenically unsaturated organic compound most preferably is cyclododecene.

[0105] In a twenty-seventh aspect the present invention relates to the use of the twenty-fifth or twenty-sixth aspect, wherein the at least one derivative of the transition metal of Group IVb, Vb and Vlb is preferably selected from a derivative of tungsten, molybdenum and vanadium, wherein the derivative more preferably is selected from salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, more preferably from alkali or alkaline earth metal salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, and most preferably is Na2WO4 or a homo- or heteropolyoxometalate formed therefrom.

[0106] In a twenty-eighth aspect the present invention relates to the use of any one of the twenty-fifth to twentyseventh aspects, wherein the homogeneous catalyst system further comprises phosphoric acid, a salt of phosphoric acid, a bisulfate, a sulfate or a combination thereof.

[0107] In a twenty-nineth aspect the present invention relates to the use of any one of the twenty-fifth to twentyeighth aspects, wherein the tertiary alcohol is tert-butanol, tert-amyl alcohol or a combination thereof.

[0108] In a thirtieth the present invention relates to the use of any one of the twenty-fifth to twenty-eighth aspects, wherein the reaction mixture comprises water, the lipophilic ethylenically unsaturated organic compound and the solvent capable of forming a thermomorphic reaction system in a weight ratio of from 5-20 wt.-% to 5-30 wt.-% to 50-90 wt.-%, based on the total combined weight of the three components, preferably of from 5-15 wt.-% to 5-25 wt.-% to 60-90 wt.-%, based on the total combined weight of the three components.

[0109] Figures

[0110] Fig. 1 shows the reaction progress of the oxidation reaction of Example 1 over time. The x-axis of the diagram indicates the reaction time in minutes. The y-axis of the diagram indicates the amount of CDAN- epoxide in weight percent, based on the total weight of the organic phase after phase separation. 202300279 Foreign Filings

[0111] 15

[0112] Examples

[0113] Example 1

[0114] A catalyst solution was prepared by dissolving sodium tungstate dihydrate (0.228 g) and 85% phosphoric acid (0.84 g) in demineralized water (5.0 g) while 50 wt.-% aqueous hydrogen peroxide (5.0 g) was added with stirring. The resulting catalyst solution was stirred at 60 °C for 15 min. 10.0 g of cyclic unsaturated C12 compound (92 wt.-% CDEN with 8 wt.-% CDAN) was stirred at 90 °C with tert-amyl alcohol (70.0 g) in a stirred tank reactor. The oxidation was started by adding the catalyst solution to the stirred tank reactor. 50 wt.-% aqueous hydrogen peroxide (2.0 g) was added after every 15 to 45 minutes.

[0115] The progress of the reaction was monitored by determining the amount of the oxidation product CDAN- epoxide using gas chromatography as described above. The results are shown in the diagram in Figure 1.

[0116] Tert-amyl alcohol was removed from the reaction mixture by distillation at 80 °C and 50 mbar. The remaining reaction mixture was extracted with demineralized water (20 g) and the organic phase was separated from the aqueous phase. The resulting aqueous phase contained 99.5 wt.% of the catalyst system (0.23 g of sodium tungstate). The resulting organic phase contained less than 40 ppm of tungstate, based on the total weight of the organic phase. The amount of tungstate in the resulting phases was determined by X-ray fluorescence spectroscopy as described above.

[0117] The resulting aqueous phase and the tert-amyl alcohol was recycled into the stirred tank reactor.

[0118] Comparative Example 1

[0119] In Comparative Example 1 an epoxidation of the cyclic unsaturated C12 compound was carried out using the same conditions as described in Example 1 , except that no tert-amyl alcohol was used in the reaction.

[0120] After a reaction time of 60 min the amount of CDAN-epoxide was determined using gas chromatography as described above. The amount of CDAN-epoxide was less than 0.1 wt.-%, based on total weight of the organic phase after phase separation.

[0121] As can be seen from the results above, it has surprisingly been found that when using a solvent capable of forming a thermomorphic reaction mixture, the oxidation of a lipophilic ethy lenically unsaturated organic compound, such as CDEN, can be performed without using a phase transfer reagent, such as a tertiary or quaternary ammonium compound. From the graph in Figure 1 , it can be seen that after a reaction time of 1 hour, approximately 10% conversion of CDEN to the corresponding epoxide is achieved and that the conversion continues to increase with time (Example 1). In contrast, when the reaction is carried out without the use of tert-amyl alcohol, there is hardly any conversion to the epoxide (Comparative Example 1). 202300279 Foreign Filings

[0122] 16

[0123] Moreover, it has been found that when using the present method, after finalizing the reaction and separating the reaction mixture the aqueous phase contains almost the entire amount of the catalyst system. This eliminates the need for recovering the catalyst from the product-containing organic phase.

Claims

202300279 Foreign Filings17CLAIMS1 . A method for the oxidation of a lipophilic ethylenically unsaturated organic compound in a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, a peroxide, a homogeneous catalyst system comprising at least one derivative of a transition metal of Group IVb, Vb and Vlb in its highest oxidation state, a solvent capable of forming a thermomorphic reaction system and water, comprising the steps of(i) providing a reaction mixture comprising the lipophilic ethylenically unsaturated organic compound, the homogeneous catalyst system, the peroxide, the solvent capable of forming a thermomorphic reaction system and water;(ii) oxidizing the lipophilic ethylenically unsaturated organic compound in the reaction mixture;(iii) forming a biphasic reaction mixture comprising an aqueous phase in which the catalyst system is concentrated by reducing the temperature and / or by distilling off at least a part of the solvent capable of forming a thermomorphic reaction system from the reaction mixture and an organic phase containing the oxidized ethylenically unsaturated organic compound; and(iv) separating the aqueous phase containing the catalyst system from the organic phase containing the oxidized ethylenically unsaturated organic compound; wherein the reaction mixture comprises less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, based on the total weight of the reaction mixture.

2. The method according to claim 1 , wherein, when the biphasic reaction mixture in step (iii) is formed by reducing the temperature, the method further comprises a step of (v) separating the solvent capable of forming a thermomorphic reaction system from the oxidized lipophilic ethylenically unsaturated organic compound.

3. The method according to claim 2, wherein in step (v) the solvent capable of forming a thermomorphic reaction system is separated by distillation.

4. The method according to any of the preceding claims, further comprising a step of (vi) further concentrating the catalyst system in the aqueous phase separated in step (iv).

5. The method according to claim 4, wherein in step (vi) the catalyst system is further concentrated by distillation and / or membrane filtration.

6. The method according to any of the preceding claims, wherein the method is carried out as a continuous process.202300279 Foreign Filings187. The method according to any of the preceding claims, wherein the catalyst system concentrated in step (vi) and / or the solvent capable of forming a thermomorphic reaction system separated in step (v) or distilled off in step (iii) is recycled to provide the reaction mixture in step (i).

8. The method according to any of the preceding claims, wherein the reaction mixture provided in step (i) forms a monophasic reaction mixture, wherein the monophasic reaction mixture preferably is formed by elevating the temperature of the reaction mixture.

9. The method according to any of the preceding claims, wherein the lipophilic ethylenically unsaturated organic compound comprises a cyclic or acyclic olefin or a combination thereof, preferably a cyclic or acyclic olefin having 6 to 20 carbon atoms, more preferably a cyclic olefin, wherein the lipophilic ethylenically unsaturated organic compound most preferably is cyclododecene.

10. The method according to any of the preceding claims, wherein the at least one derivative of the transition metal of Group IVb, Vb and Vlb is selected from a derivative of tungsten, molybdenum and vanadium, wherein the derivative preferably is selected from salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, more preferably from alkali or alkaline earth metal salts of H2WO4 or H2MOO4, or homo- or heteropolyoxometalates formed therefrom, and most preferably is Na2WO4 or a homo- or heteropolyoxometalate formed therefrom.1 1 . The method according to any of the preceding claims, wherein the homogeneous catalyst system further comprises phosphoric acid, a salt of phosphoric acid, a bisulfate, a sulfate or a combination thereof.

12. The method according to any of the preceding claims, wherein the solvent capable of forming a thermomorphic reaction system comprises a tertiary alcohol, preferably a tertiary alcohol having a boiling temperature lower than that of the oxidized organic compound, more preferably tertbutanol, tert-amyl alcohol or a combination thereof.

13. The method according to any of the preceding claims, wherein the peroxide comprises hydrogen peroxide.

14. A method for synthesizing a lactam, comprising: epoxidizing a cyclic lipophilic ethylenically unsaturated organic compound to an epoxide; rearranging the epoxide to a ketone; converting the ketone to an oxime; and rearranging the oxime to lactam; wherein the cyclic lipophilic ethylenically unsaturated organic compound is epoxidized according to the method of any of claims 1 to 13.202300279 Foreign Filings1915. A mixture comprising tungsten in an amount of more than 1000 ppm, phosphorous in an amount of more than 10 ppm, hydrogen peroxide in an amount of from 0.05 to 5.0 wt.-%, a lipophilic ethylenically unsaturated organic compound and an oxidation product of the lipophilic ethylenically unsaturated organic compound in a combined amount of at least 5 wt.-% and not more than 80 wt.-%, a tertiary alcohol in an amount of at least 10 wt.-% and less than 95 wt.-%, and less than 0.1 wt.-% of a tertiary amine or quaternary ammonium compound, wherein wt.-% is based on the total weight of the mixture.

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