Process for oxidizing cyclic ketones

Abstract

The invention relates to an improved Baeyer-Villiger oxidation process of cyclic ketones to lactones in the presence of oxygen and an aldehyde.

Description

[0001] UNIVERSITY OF BIELEFELD Düsseldorf, August 8, 2025

[0002] Our reference number: UD 42415 / SAM

[0003] Bielefeld University

[0004] Universitätsstraße 25, 33615 Bielefeld, Germany

[0005] Methods for the oxidation of cyclic ketones

[0006] Description

[0007] The present invention relates to the field of the oxidation of ketones, in particular cyclic ketones, to esters or lactones. The research leading to this invention was funded by the BMBF project “BioCapa”, file number D-2110-0301-0043-2100.

[0008] The basic reaction type, the so-called Bayer-Villiger oxidation, has been known since 1899 and is used on a large scale, especially for the production of caprolactone (exact name: 8-caprolactone), the starting material for polycaprolactone (PCL) or other interesting polymers.

[0009] Traditionally, peracids were used for this oxidation of ketones; however, decades ago, due to the potential explosiveness of the starting materials and also for economic reasons, oxidation with oxygen was considered. This requires an additional reactant, usually an aldehyde, which is then also oxidized. Benzaldehyde is frequently used in this process.

[0010] However, the challenge lies in creating improved reaction conditions for the oxidation of cyclic ketones. This challenge is addressed by a process according to claim 1. Accordingly, a process for the oxidation of cyclic ketones to lactones in the presence of oxygen is proposed, comprising the step

[0011] Contacting a mixture comprising a cyclic ketone and an aldehyde with oxygen, wherein the molar ratio of cyclic ketone and aldehyde is >1.

[0012] Surprisingly, it has been found that lactones can be efficiently produced from the corresponding ketones in this way. This is surprising because the prior art uses an excess of aldehyde.

[0013] The preferred cyclic ketone is selected from substituted, preferably alkyl-substituted and unsubstituted Cs-Cs ketones, preferably Ce ketones. The ketone cyclohexanone is most preferred. Hydrogenated cardanol, which can be obtained as a bio-based raw material, is also a preferred cyclic ketone.

[0014] Preferably, the aldehyde is a substituted, preferably alkyl-substituted or unsubstituted aliphatic C2-Cs aldehyde. Most preferred are C3-C5 aldehydes, even more preferred are butyraldehyde (w-butanal) and isobutyraldehyde, most preferably butyraldehyde.

[0015] These aldehydes have proven particularly useful because they allow for simple purification (see below). Furthermore, butyraldehyde (n-butanal) and isobutyraldehyde, for example, are produced on an industrial scale by hydroformylation of propylene and are therefore extremely inexpensive.

[0016] According to a preferred embodiment of the invention, the molar ratio of cyclic ketone and aldehyde is >1 to <1000. More preferably, the molar ratio of cyclic ketone and aldehyde is >1.1 to <100, more preferably >1.5 to <50, more preferably >1.8 to <20, and more preferably >2 to <10.

[0017] According to a preferred embodiment of the invention, the oxygen overpressure is between 0 and 10 bar. Both pure oxygen and atmospheric oxygen can be used. Since oxygen is consumed during the reaction, a sufficient oxygen concentration is advantageous. The process is preferably carried out in a closed system, with oxygen gas being supplied to the reaction solution. A closed system is preferred because, in an open system, the aldehyde can be removed from the reaction mixture along with the supplied oxygen gas at elevated temperatures. This can uncontrollably alter the aldehyde concentration and thus the reaction conditions.

[0018] According to a preferred embodiment of the invention, the method comprises the steps: a) providing the cyclic ketone b) adding the aldehyde in the simultaneous presence of oxygen

[0019] Step b) can be carried out continuously within 0.5 h to 82 h, preferably within 3 h to 24 h. The change in aldehyde concentration in the reactor, depending on the dosage, can range between 0.1 and 1000 mmol(aldehyde) mol. -1 (Ketone) h' 1 The concentration of the added aldehyde can be kept constant or varied along a gradient over the entire reaction period.

[0020] According to a preferred embodiment, the dosing rate for continuous addition of the aldehyde is >6 to <500 mmol(aldehyde) mol(ketone)' 1 h' 1 , especially preferably >6 to <50 mmol(aldehyde) mol(ketone) -1 h' 1 At this dosing rate, the lactone yield can be increased. According to a preferred embodiment, with continuous addition of the aldehyde, the initial aldehyde concentration is >50 and

[0021] <120 mmol(aldehyde) / mol(ketone). This concentration has proven advantageous, as above this range sufficient oxygen supply to the solution may be impaired, potentially leading to reduced reaction selectivity. Below this concentration, the reaction has sometimes been observed to start with a delay, which could be due to insufficient radical formation through aldehyde autoxidation to initiate the reaction.

[0022] According to a preferred embodiment of the invention, the process is carried out in the presence of a solvent. Preferred solvents are esters, in particular ethyl acetate.

[0023] According to a preferred embodiment of the invention, the solvent does not include 1,2-dichloroethane, acetonitrile, benzene, or toluene. The autoxidation rate of the aldehyde must be considered when selecting the solvent. The autoxidation of the aldehyde in cyclohexanone as a solvent is slower than with traditional solvents such as ethyl acetate. Faster autoxidation allows for a greater conversion of aldehyde more quickly and an increased addition rate, while slower autoxidation can increase selectivity.

[0024] According to an alternative preferred embodiment, the process is carried out without solvents. This has proven particularly advantageous due to the ease of processing.

[0025] According to a preferred embodiment of the invention, the reaction is carried out in the presence of a catalyst. Preferred catalysts include metal oxides, chlorides and acetates, in particular cobalt, iron, zinc, manganese, magnesium, tungsten, nickel, and mixtures thereof, talcites and hydrotalcites, and phosphates, in particular comprising iron and / or zinc.

[0026] Preferably the amount of catalyst is <2 ppm, based on the originally used cyclic ketone, more preferably > 1 ppb and <1 ppm, and most preferably > 10 ppb and <0.5 ppm.

[0027] According to an alternative embodiment, the process is carried out without a catalyst. Surprisingly, for many applications within the scope of the present invention, it has been found that good yields can be obtained while simultaneously avoiding further byproducts. A particular advantage of the catalyst-free variant is that, during distillative work-up with optional solvent removal, no catalyst accumulation occurs, thus preventing an increased catalytic formation of undesired side reactions.

[0028] The process is preferably carried out at a temperature of >10°C to <100°C, more preferably at >20°C to <50°C, and most preferably at >40°C to <50°C. Surprisingly, compared to higher reaction temperatures, no adipic acid is formed as a byproduct at <50°C, resulting in improved product purity. The detrimental formation of adipic acid was observed in the prior art.

[0029] According to a preferred embodiment of the invention, the lactone, which is the target product of the present process, is obtained by distillation.

[0030] According to a preferred embodiment, the process is carried out without an additional initiator, such as ozone, AIBN, or similar initiators. This has the advantage that no contamination from further additives occurs and the reaction can be initiated by the autoxidation of the aldehyde itself. A procedure comprising the following steps is particularly preferred: i. Optionally, taking a portion of the reaction mixture; ii. Purifying the reaction mixture or the portion of the reaction mixture taken in step i. by distillation; iii. Obtaining the reaction product from the distillation residue or by distillation.

[0031] For clarification:

[0032] Especially when no solvent and no catalyst are used, the reaction mixture essentially comprises four components:

[0033] - Unreacted cyclic ketone

[0034] - Unreacted aldehyde

[0035] - Lactone

[0036] Carboxylic acid obtained from the aldehyde

[0037] If cyclohexanone and isobutyraldehyde are chosen as starting materials, the lactone (caprolactone) has the highest boiling point at 235°C, so that after distilling off the other components, this product can be obtained from the distillation residue. Depending on the application, complete distillation is of course also advantageous; in the case of caprolactone, however, this would have to be carried out at reduced pressure, since caprolactone partially decomposes at higher temperatures.

[0038] If a catalyst is present, a separation step might be necessary; if a solvent is present, it would also be distilled off. The aforementioned components, as well as those claimed and described in the exemplary embodiments, are not subject to any special exceptional conditions with regard to their size, shape, material selection, and technical design, so that the selection criteria known in the field of application can be applied without restriction.

[0039] Further details, features and advantages of the subject matter of the invention will become apparent from the dependent claims as well as from the following description of the figures and examples, which are purely illustrative and not to be regarded as limiting.

[0040] This shows

[0041] Fig. 1 shows the aldehyde efficiency of reaction 1t. Example 1;

[0042] Fig. 2 shows a representation of the concentration gradient of reaction 1t. Example 2;

[0043] Fig. 3 shows a representation of the change in the amount of substance in reaction 1t. Example 2;

[0044] Fig. 4 shows a representation of the conversions of reactions 1t. Example 3;

[0045] Fig. 5 shows a representation of the conversions of reactions 1t. Example 4;

[0046] Figures 6 to 8 show the conversions of reactions 1t. Example 5;

[0047] Fig. 9 shows a representation of the conversions of reaction 1t. Example 6;

[0048] Figs. 10, 11 Representations of the solvent change of reactions 1t. Example 7; Fig. 12 Representations of the aldehyde concentration change of reactions 1t.

[0049] Example 8; as well as

[0050] Fig. 13 Representation of the conversions of reaction 1t. Example 9.

[0051] Example 1: Investigation of different aldehyde concentrations:

[0052] The yields (based on the butyraldehyde used) for the following reaction were investigated: 20 mmol

[0053] Cyclohexanone (1.96 g, 20 mmol) was presented and the aldehyde (1t. example) was added.

[0054] The reaction mixture was stirred under an oxygen atmosphere for 20 hours (600 rpm).

[0055] The results can be seen in Table 1 below and in Fig. 1:

[0056] Table 1:

[0057] As can be clearly seen, the yield (relative to the efficiency of the butyraldehyde used) increases significantly when, according to the invention, it is used in a reduced quantity. Furthermore, the yield can be increased even more if the aldehyde is not added all at once at the beginning, but rather in measured doses.

[0058] Example 2: Influence of the amount of aldehyde on the aldehyde efficiency

[0059] In a further experiment, the influence of the amount of aldehyde on the aldehyde efficiency was investigated. The following basic reaction scheme was used as a basis.

[0060] The efficiency (i.e., the conversion of cyclohexanone to caprolactone compared to the conversion of aldehyde to carboxylic acid) is shown in Fig. 1 for isobutyraldehyde and butyraldehyde, each for equimolar amounts (comparison) as well as for 0.5 and 0.1 equivalents, respectively. It is clearly visible that the conversion increases with respect to the amount of aldehyde used as the amount of aldehyde decreases.

[0061] Furthermore, a scale-up of the reaction was carried out under / / cv / Z conditions (without the addition of solvent) with butyraldehyde, according to the following scheme:

[0062] The aldehyde was added to the reaction mixture in two intervals, each lasting 20 hours. After the addition of the aldehyde, the system was stirred at 50°C for 24 hours. Figures 2 and 3 show the concentration gradient and change in the amount of substance of the aldehyde during the reaction.

[0063] The amounts of cyclohexanone and butyraldehyde used are given in Table 2 below.

[0064] Table 2: Amounts of cyclohexanone and butyraldehyde used.

[0065] Table 3 shows the obtained process parameters. Table 3: Obtained process parameters during the scale-up trial.

[0066] A high mass balance of 95% was achieved, with a conversion to caprolactone of 13%. After isolation of the caprolactone, the yield was 72%. A similarly high aldehyde efficiency of 30% was also achieved.

[0067] Example 3: Influence of the oxidizing agent

[0068] Furthermore, the influence of the oxidizing agent was investigated. For this purpose, the oxidation of cyclohexanone with isobutyraldehyde (3 equivalents) was carried out under the influence of pure oxygen and compressed air according to the following scheme:

[0069] The conversions of this reaction are shown in Fig. 4. Oxidation with pure oxygen proceeds faster than with compressed air, but similar conversions are achieved at the end of the reaction.

[0070] Example 4: Influence of the aldehyde dosage

[0071] The influence of the aldehyde dosage was also investigated. For this purpose, a

[0072] Oxidation carried out using isobutyraldehyde, according to the following scheme:

[0073] The results are shown in Fig. 5. It is clearly evident that increasing the dosage of the aldehyde has a positive effect on the conversion to caprolactone. With a dosage of 10 mmol / h, a conversion of over 55% was achieved after just a few hours.

[0074] Example 5: Influence of different metal catalysts. The influence of metal catalysts during the BVO with benzaldehyde was also investigated. The conversions for 0.5 equivalents of benzaldehyde can be seen in Fig. 6 and are shown in Table 4 (next page): 50°C, 3 h, neat

[0075]

[0076] Table 4: Sales for 0.5 equivalents of benzaldehyde with metal catalysts

[0077] It can be seen that no substantial increase in aldehyde efficiency can be achieved through the use of catalysts. Likewise, high product concentrations between 15 and 22 g / L can be achieved. 1can be achieved.

[0078] The experiments were repeated for different aldehyde concentrations in ethyl acetate as solvent and without solvent ("neate"), the results are shown in Figures 7 and 8. Here too, it can be seen that (with one exception, ZnCh at 0.5 eq. aldehyde "neate") no significant differences were observed.

[0079] Example 6: Influence of dosing rate

[0080] In a further experiment, the aldehyde dosing rate was investigated over a period of 24 hours at a temperature of 20–50 °C in a closed system. During the reaction, oxygen gas is introduced into the reaction solution and stirred using a KPG stirrer at 500–2000 rpm. The reaction is started with 0–2 M aldehyde as the initiator, and the aldehyde dosing rate is set to 0.0089 mL / min. No adipic acid is obtained as a byproduct in this reaction at the mild reaction temperature. The increase in caprolactone yield at the low dosing rate is shown in Fig. 9.

[0081] Example 7: Influence of the solvent on the autoxidation rate

[0082] In a further experiment, the autoxidation rate of the aldehyde in various solvents at 40 or 50 °C is investigated. Figures 10 and 11 show that the autoxidation of the aldehyde in cyclohexanone as a solvent is slower than with traditional solvents such as ethyl acetate. This has an impact on the addition rate of the aldehyde, since faster autoxidation rates allow for a greater conversion of aldehyde more quickly.

[0083] R = "Pr

[0084] Response to Fig. 11.

[0085] Example 8: Influence of aldehyde concentration on the autoxidation rate

[0086] The autoxidation of the aldehyde was investigated in a further experiment at various aldehyde concentrations. Figure 12 shows an S-shaped decrease in the aldehyde concentration at low initial aldehyde concentrations of 0.55 mmol / g ketone. This could presumably be explained by the radical nature of the reaction. A sufficient number of radicals must initially be generated for the reaction to proceed efficiently. At higher aldehyde concentrations, these radicals are available more quickly, thus enabling a higher maximum reaction rate.

[0087] With increasing initial aldehyde concentration, a concentration limit is reached at 1.18 mmol / g ketone, presumably due to insufficient oxygen entering the solution. A reaction above this initial concentration reduces the selectivity of the process.

[0088] Figure 12 shows the fitted curves of the aldehyde concentration for Example 8, as well as the first derivatives. These reveal a maximum rate of decrease at approximately 29 pmol / g min, as also shown in Table 5 below. This suggests that it may be advantageous to maintain a suitable concentration range for the initial aldehyde and to control the rate of addition within an appropriate range. Table 5: Initial concentration of the aldehyde and maximum rate of decrease. Example 9: Influence of the ketone with different aldehydes.

[0089] The influence of the ketone with various aldehydes was also investigated. For this purpose, an oxidation using hydrogenated cardanol with different aldehydes was carried out according to the following scheme:

[0090] The comparative experiments for the different aldehydes were carried out here with an excess of aldehyde (3 eq). The results of the reaction of hydrogenated cardanol with various aldehydes are shown in Fig. 13. It is clearly evident that hydrogenated cardanol can also be successfully used as a bio-based raw material in the reaction.

[0091] The individual combinations of components and features of the embodiments already mentioned are exemplary; the exchange and substitution of these teachings with other teachings contained in this publication and with the cited publications are also expressly considered. The person skilled in the art recognizes that variations, modifications, and other embodiments described herein may also occur without deviating from the inventive concept and scope of the invention. Accordingly, the above description is exemplary and not to be considered limiting. The word "comprise" used in the claims does not exclude other components or steps. The indefinite article "a" does not preclude the meaning of a plural. The mere fact that certain dimensions are cited in mutually different claims does not indicate that a combination of these dimensions cannot be used to advantage.The scope of the invention is defined in the following claims and their equivalents.

Claims

Patent claims 1. Method for the oxidation of cyclic ketones to lactones in the presence of oxygen, comprising the step: Contacting a mixture comprising a cyclic ketone and an aldehyde with oxygen, wherein the molar ratio of cyclic ketone and aldehyde is >1.

2. The method according to claim 1, wherein the cyclic ketone is selected from substituted, preferably alkyl-substituted and unsubstituted Cs-Cs ketones.

3. Method according to claim 1 or 2, wherein the aldehyde is selected from substituted, preferably alkyl-substituted or unsubstituted aliphatic C2-C8 aldehydes.

4. Method according to any one of claims 1 to 3, wherein the molar ratio of cyclic ketone and aldehyde is >1.1 to <100.

5. A method according to any one of claims 1 to 4, wherein the method comprises the steps: a) providing the cyclic ketone; b) adding the aldehyde in the simultaneous presence of oxygen.

6. Method according to claim 5, wherein in step b) the aldehyde is added within 0.5 to 82h.

7. A method according to any one of claims 1 to 6, wherein the method is carried out in the presence of a solvent, preferably selected from esters, in particular ethyl acetate.

8. A method according to any one of claims 1 to 6, wherein the method is carried out without solvents.

9. A process according to any one of claims 1 to 8, wherein the process is carried out in the presence of a catalyst, preferably selected from metal oxides and acetates, in particular cobalt, iron, antimony, manganese, magnesium, tungsten, nickel, and mixtures thereof, talcites and hydrotalcites, and phosphates, in particular comprising iron and / or zinc, wherein the amount of catalyst is preferably <2 ppm 10. A method according to any one of claims 1 to 8, wherein the method is carried out without a catalyst.

11. Method according to any one of claims 1 to 10, wherein the method is carried out at a temperature of >20 to <50 °C.

12. Method according to any one of claims 1 to 11, wherein the method is carried out without an additional initiator.

13. A method according to any one of claims 1 to 12, wherein the initial concentration of the aldehyde is >50 and <120 mmol (aldehyde) / mol (ketone).

14. A method according to any one of claims 1 to 13, wherein the dosing rate of the aldehyde is >6 to <500 mmol (aldehyde) / mol (ketone). 1 h' 1 lies.

15. Method according to any one of claims 1 to 14, wherein the method is carried out in a closed system with oxygen supply.

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