Process for preparation of 1, 1, 4, 4-tetraalkoxy-2-butene

Abstract

The present invention relates to a novel process for the preparation of alkoxylated 2, 5-dihydrofuran.

Description

[0001] The present invention relates to a new process for the preparation of 1,1,4,4-tetraalkoxy-2-butene.

[0002] 1,1,4,4-tetraalkoxy-2-butene (compound of formula (I)) is a very useful class of compounds, wherein R, R1and R2are independently of each other linear or branched C1-C6alkyl.

[0003] For example, 1,1,4,4-tetramethoxy-2-butene (wherein R, R1and R2are all -CH3) is an important intermediate for the synthesis of carotenoids (known from prior art, for example from CN 108752178 A).

[0004] The prior art discloses various processes for the production of 1,1,4,4-tetraalkoxy-2-butene. One of the syntheses is shown in the following reaction scheme: wherein (2Z)-but-2-ene-1,4-diol (compound of formula (II)) is alkylated in the first step (step (i)), wherein 2,5-dihydro-2,5-dialkoxyfuran is obtained, and then in the second step (step (ii)) the desired product (compound of formula (I)) is obtained.

[0005] Due to the importance of the compounds of formula (I), there is always a need to improve the synthesis of these compounds.

[0006] Surprisingly, it has been found that when the process is carried out under specific conditions, the compounds of formula (I) are obtained in excellent yield and the waste of the new process is kept at a very low level.

[0007] As mentioned above, the process according to the present invention consists of two steps (step (i) and step (ii)).

[0008] These steps will be discussed in more detail below.

[0009] Step (i) This step is carried out electrochemically. Step (i) can be carried out as described in WO2006 / 100289, wherein the 2,5-dihydrofuran derivative (compound of formula (III)) is obtained by electrochemical oxidation in the presence of a C1-monalkyl alcohol to a C6-monalkyl alcohol.

[0010] Using an anode and a cathode made of graphite, a yield of 46% of 2,5-dimethoxy-2,5-dihydro-furan was obtained. The selectivity was 51%.

[0011] Electrochemical reactors (cells) with a specific arrangement can also be used.

[0012] A rectangular electrochemical reactor with vertical flow can be used to prepare compounds of formula (III).

[0013] Step (i) includes a method for preparing a compound of formula (III). , Where R is a straight-chain or branched C1-C6 alkyl group. The method includes: electrochemically reacting a compound of formula (II) in the Z-form with at least one monohydric alcohol of formula (IV). ROH (IV), Where R has the same meaning as in the compound of formula (III), Its features are, The method is carried out in an electrochemical reactor with vertical flow.

[0014] It can be seen that when used in the method according to the present invention, formula (II) is of the Z-form.

[0015] However, a small amount of the E-form of compound (II) can also be used. Based on the total weight of the compound of formula (II) in this method, the E-form can be present in an amount of less than 5% by weight.

[0016] The preferred compounds of formula (III) are those compounds, wherein R is -CH3 or -CH2CH3.

[0017] More preferably, the compound of formula (III), wherein R is -CH3.

[0018] The method of the present invention is typically carried out in a non-aqueous medium, which serves as the solvent.

[0019] In the context of this invention, the term "non-aqueous" means that, based on the total weight of the non-aqueous medium, less than 50% by weight of water may be present in the non-aqueous medium.

[0020] Generally, the term "non-aqueous" means that, based on the total weight of the non-aqueous medium, less than 20% by weight of water can be present in the non-aqueous medium.

[0021] Non-aqueous media typically contain at least one straight-chain or branched C1-C. 10The alcohol is used as a solvent, preferably at least one straight-chain or branched C1-C6 alcohol, more preferably ethanol or methanol, and even more preferably methanol. Most preferably, the non-aqueous medium comprises a straight-chain or branched C1-C6 alcohol, wherein the non-aqueous medium is the same as the monohydric alcohol of formula (IV) above.

[0022] This means that the monohydric alcohol of formula (IV) can also be used as a non-aqueous medium, or it can be a mixture of other alcohols with the monohydric alcohol of formula (IV).

[0023] Preferably, the monohydric alcohol of formula (IV) is also used as a non-aqueous medium.

[0024] The amount of alcohol in at least one of the compounds of formula (IV) is at least 2 molar equivalents relative to the compounds of formula (II). This means that the alcohol is always present in at least this amount when not used as a non-aqueous medium.

[0025] Of course, the non-aqueous medium may also be at least one alcohol of the compound of formula (III).

[0026] Advantageously, the reaction in step (i) is carried out in an electrochemical reactor with vertical flow, as better results can be obtained. This means that the flow of the reaction mixture can be from bottom to top or from top to bottom in the electrochemical reactor. Preferably, the vertical flow of the reaction mixture in the electrochemical reactor is from bottom to top. This is typically accomplished by a pumping system.

[0027] Preferably, the flow of the reaction mixture is a circulating flow that begins in the reservoir and then returns to the reservoir, and more preferably, the flow within the electrochemical reactor is a vertical flow from bottom to top.

[0028] The size, shape, and therefore volume of an electrochemical reactor can vary. The size, shape, and volume of an electrochemical reactor are not essential characteristics. A very common and preferred form is a rectangular shape.

[0029] The flow rate of the starting material can be varied. This depends on the size, shape, and volume of the rectangular electrochemical reactor.

[0030] The typical flow rate is at least 10 mL / min. The typical and preferred range is 10 mL / min to 1000 mL / min.

[0031] The electrodes (cathode and electrode) used in the method according to the invention may be made of any common material, or may be made of more than one material, such as a metal on a carrier material or a metal oxide on a carrier material.

[0032] In this method, the target product is formed on the anode, and dihydrogen is deposited at the cathode. Therefore, using a metal or alloy instead of graphite (which is commonly used in existing technologies) as the cathode is advantageous because they are more reactive in dihydrogen production. Another advantage of using a metal or alloy as the cathode is the significant reduction in cell potential, which results in energy savings in this method.

[0033] Examples of cathode materials that can be used include metals, graphite, iron, metal alloys (e.g., steel), and precious metals (e.g., platinum).

[0034] As described above, in a preferred embodiment of the present invention, the cathode is not made of graphite.

[0035] Materials that are stable under electrolytic conditions are used for the anode. Examples of such materials are noble metals (e.g., platinum), oxides (e.g., ruthenium dioxide on titanium), graphite, highly oriented pyrolytic graphite (HOPG), boron-doped diamond (BDD), dimensionally stable anode (DSA), and glassy carbon.

[0036] Electrodes can be in any common form. Such forms can be plates, wires, rods, cells, screens, meshes, sponges, or any other commonly used design.

[0037] The size of the electrode used in the method according to the invention can vary, and it depends on the size, form, and structure of the electrochemical reactor (cell).

[0038] The typical size is at least 10 cm. 2 (For each battery). The upper limit of the electrodes is not that critical.

[0039] Typically, the cathode and anode have the same dimensions, but this is not always the case.

[0040] The reaction medium typically and preferably contains at least one electrolyte. It may be added to the reaction medium in the form of a salt and / or an acid. Any known and commonly used electrolyte may be used, except for phosphoric acid and / or any salt thereof.

[0041] For example, suitable supporting electrolytes are HCl, H2SO4, Na2SO4, NaCl, sodium dodecyl sulfate, methyltributylmethylammonium sulfate, triethylammonium bisulfate, tetrabutylammonium bisulfate, tetramethylammonium bisulfate, tetrabutylammonium acetate (NBu4OAc), tetrabutylammonium sulfate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, methanesulfonic acid, ammonium bisulfate, tetrabutylphosphine methanesulfonate, 1-methylimidazolium hydrogen sulfate, tetrabutylammonium perchlorate, and LiClO4.

[0042] Typically, at least one electrolyte with a concentration up to 2 M is used, preferably 0.01-1 M, more preferably 0.1-0.5 M, 0.2-0.5 M.

[0043] In a preferred embodiment, the electrolyte is not phosphate and / or its salts.

[0044] The reaction medium according to the method of the present invention preferably has a pH value between 0 and 7 at the beginning of the method.

[0045] The method according to the invention is carried out at a temperature of 0°C to 75°C (preferably 0°C to 60°C, more preferably 15°C to 40°C).

[0046] The method according to the invention is typically carried out at ambient temperature.

[0047] Depending on the battery, the method according to the invention can be performed in batches or continuously. A continuous method is preferred.

[0048] The current density used in the method according to the invention is preferably 1-1000 mA / cm². 2 Preferably, 10-1000 mA / cm 2 More preferably 20-1000 mA / cm 2 .

[0049] The potential between the anode and cathode can be 12V or less. A suitable range is 0.5-12V, preferably 0.5-10V; more preferably 0.5-8V; and most preferably 1-8V.

[0050] The method according to the present invention can be performed in constant current or constant potential mode.

[0051] The reaction products can be separated using known methods.

[0052] The essential features of the novel method according to the invention are the recycling of unreacted alcohol of formula (IV), recycling to an electrolyte, and removal of water from the reaction mixture of step (i).

[0053] First, unreacted alcohols and electrolytes of formula (IV) are removed using nanofiltration. Then, prior to step (ii) of this method, the reaction mixture thus treated is pervaporated to remove water from the reaction.

[0054] Nanofiltration is typically used to recycle alcohols and electrolytes from the reaction mixture. This can be multi-stage nanofiltration.

[0055] This nanofiltration is typically and preferably performed using a membrane.

[0056] Permeate easily crosses the membrane, while residue cannot cross the membrane, or at least crosses it in significantly less amount. Higher molecular weight substances are part of residue, while lower molecular weight substances are part of permeate.

[0057] Various membranes exist, each with its own molecular weight cut-off (MWCO) characteristics. Membrane materials can be inorganic or organic.

[0058] Of course, it is important that the membrane is stable to the solvents used and resistant to the reaction conditions selected during nanofiltration.

[0059] However, it has been shown that polymer membranes, preferably siloxane-based membranes, and most preferably siloxane-based composite membranes, are particularly suitable for nanofiltration. The most preferred type is a PDMS / PAN (polydimethylsiloxane / polyacrylonitrile) based membrane.

[0060] Since MWCO is an important property of membranes used for separating low-molecular-weight and high-molecular-weight substances, it is preferred for the present invention to use membranes with MWCO between 100 and 1000 Daltons, and more preferably between 150 and 650 Daltons.

[0061] Suitable membranes for nanofiltration can be purchased from various suppliers. For example, one such membrane is the PURAMEM from Evonik. ® And from Borsig GmbH, Solsep BV, UNISOL Membrane Technology or Inopor.

[0062] Preferably, nanofiltration is carried out under elevated pressure, typically and preferably, the applied pressure is between 1 and 60 bar, more preferably between 2 and 60 bar, more preferably between 5 and 50 bar, even more preferably between 10 and 50 bar, and most preferably between 15 and 50 bar.

[0063] Preferably, nanofiltration is carried out at a temperature between 15°C and 70°C, more preferably between 15°C and 60°C, and even more preferably between 20°C and 50°C.

[0064] Devices used for nanofiltration are known to those skilled in the art.

[0065] It has been shown that nanofiltration of organic solvents is particularly preferably carried out in a cross-flow mode.

[0066] In cross-flow mode, the feed flows tangentially across the membrane surface and perpendicular to the permeate flux.

[0067] In a particularly preferred manner, filtration is performed in a multi-stage nanofiltration process. This means that more than one nanofiltration step is performed.

[0068] The reaction mixture from this (nano)filtration process is further processed to remove water.

[0069] This is typically and preferably carried out via pervaporation.

[0070] For pervaporation, a specific membrane is usually used.

[0071] The membrane needs to be stable against the solvents used and resistant to the reaction conditions selected during pervaporation.

[0072] However, it has been shown that polymer membranes, preferably polyvinyl alcohol-based membranes, are particularly suitable for pervaporation.

[0073] Suitable membranes for pervaporation are commercially available from various suppliers, such as Deltamem or Pervatech.

[0074] Preferably, pervaporation is carried out under elevated pressure, typically and preferably, the applied pressure is between 0.1 and 30 bar, more preferably between 0.5 and 20 bar, more preferably between 1 and 30 bar, and most preferably a pressure of 1-20 bar is applied at the permeate site, and an absolute pressure of 0.1-10 millibars is applied at the permeate site.

[0075] Preferably, the pervaporation is carried out at a temperature between 15°C and 90°C, more preferably between 15°C and 80°C, and even more preferably at an elevated temperature of 30°C and 80°C.

[0076] Devices for pervaporation are known to those skilled in the art.

[0077] The reaction mixture thus treated is then used in step (ii) to produce the compound of formula (I).

[0078] Step (ii) The reaction method of step (ii) is known from the prior art, for example from WO2021 / 170864A1, WO 2006 / 108664 and EP 581097.

[0079] Therefore, the method of step (ii) can be carried out according to any method known in the prior art (in particular from WO2021 / 170864A1, WO2006 / 108664 and EP 581097).

[0080] The preferred reaction conditions are those known from WO2021 / 170864A1.

[0081] The reaction in step (ii) can be carried out in the presence of a catalyst and an alcohol of formula (Va) and / or (Vb). R1-OH (Va) R2-OH (Vb), in R1 is a straight-chain or branched C1-C6 alkyl group, and R2 is a straight-chain or branched C1-C6 alkyl group.

[0082] Preferably, R1 is CH3 or -CH2CH3.

[0083] Preferably, R1 is CH3 or -CH2CH3.

[0084] More preferably, R1 is CH3.

[0085] More preferably, R2 is CH3 or -CH2CH3.

[0086] This means that a mixture of alcohols or pure alcohols can be used, where R1 and R2 are the same part.

[0087] Suitable catalysts can be acidic ion exchangers. Such anion exchangers typically have an acid site concentration of at least 2.5 eq / kg, preferably at least 3.0 eq / kg, more preferably at least 4.0 eq / kg, and most preferably 5.0 eq / kg.

[0088] In a more preferred embodiment, the catalyst is an acidic ion exchanger containing sulfonic acid groups and having an acid site concentration of at least 2.5 eq / kg, preferably at least 3.0 eq / kg, more preferably at least 4.0 eq / kg, and most preferably 5.0 eq / kg.

[0089] The preferred catalyst is an acidic ion exchanger with a particle size distribution greater than or equal to 400 micrometers and a water retention capacity of <60%, preferably in the range of 40-60%, and more preferably in the range of 50-60%, or an acidic ion exchanger with a particle size distribution of <400 micrometers and a water retention capacity of >60%, preferably in the range of 60-80%, and more preferably in the range of 60-75%.

[0090] The molar ratio of the compound of formula (III) to the alcohols of formulas (Va) and (Vb) is preferably in the range of 1:45 to 1:100, more preferably in the range of 1:50 to 1:90, even more preferably in the range of 1:60 to 1:80, and most preferably in the range of 1:70 to 1:80.

[0091] The resulting compound of formula (I) can be isolated and, if desired, further purified.

[0092] As mentioned above, compounds of formula (I) (such as 1,1,4,4-tetramethoxy-2-butene, wherein R, R1 and R2 are all -CH3) are important intermediates in the synthesis of carotenoids (known from the prior art, for example from CN 108752178 A).

[0093] The following examples are provided to illustrate the present invention. Unless otherwise stated, all quantities given are by weight, and temperatures are given in °C.

[0094] Example Step (i) (electrolysis of compound R=CH3 of formula (II)) Electrochemical oxidation of 1 M Z-2-buten-1,4-diol (2.96 mol) to 2,5-dihydro-2,5-dimethoxyfuran (DMDF) was carried out in an undivided flow cell (2 V = 10 mL, surface area 100 cm²). 2 The experiment was conducted in methanol (with an electrode distance of 1 mm), using 5.5 wt% triethylamine and 4.1 wt% sulfuric acid as electrolytes. Graphite (100 cm) 2 The electrode is used as the anode, and it is made of stainless steel (100 cm). 2 (This is used as the cathode.) By applying 150 mA / cm at 20°C... 2Electrolysis was performed at a constant current density (measured cell potential 6.4 V). The reaction mixture was pumped through a flow cell at a flow rate of 20 L / h. After 1440 min, 90% conversion of 2-butene-1,4-diol (BED) was achieved, with 70% selectivity for DMDF at a Faraday efficiency of 56%.

[0095] Nanofiltration after step (i) The reaction mixture obtained in step (i) has been subjected to two-stage nanofiltration. In the two organic solvent nanofiltration units, a surface area of ​​42 cm² was used. 2 The membrane was subjected to pressure of 40 bar at 25°C by Evonik PuraMem Performance (Evonik Industries AG, Germany).

[0096] After nanofiltration of the starting solution and application of 1 percolation volume (DV) of methanol, the composition of percolate 1 was analyzed and is indicated in Table 1. The percolate was used as the starting solution for a second organic solvent nanofiltration unit using the same setup. After nanofiltration and application of 1.3 percolation volumes (DV) of methanol, the composition of percolate 2 from the second organic solvent nanofiltration unit was analyzed and is indicated in Table 1. As a measure of overall separation performance, the ratio of DMDF to electrolyte is given for the starting solution (the electrolytic reaction mixture introduced into the first organic solvent nanofiltration unit) and the percolates from both the first and second organic solvent nanofiltration units, as shown in Table 1.

[0097] The comparison of results shown in Table 1 indicates that the OSN membrane, in particular, exhibits excellent separation performance according to Evonik PuraMem Performance. Throughout both stages of the OSN process, 99.3% of the used electrolyte was recovered and separated from the DMDF.

[0098] Table 1: Pervaporation after nanofiltration The permeate OSN obtained after nanofiltration was pervaporated. In the pervaporation unit, a device with a diameter of 170 cm⁻¹ was used at 70°C. 2 The surface area of ​​the membrane DeltaMem PERVAP 4101 (DeltaMem AG) is such that a pressure of 15 bar is applied at the permeate site and an absolute pressure of 1 millibar is applied at the permeate site.

[0099] After 74 hours of pervaporation, the composition of the permeate was analyzed and indicated in Table 2 (MeOH washing refers to additional equipment washing, solution unified). As a measure of overall performance, the water content of the starting solution (permeate OSN stage 2) and the permeate is given in Table 2.

[0100] The comparison of results shown in Table 2 indicates that the water content of the DMDF-containing solution is significantly reduced.

[0101] Table 2 Results of the pervaporation step Step (ii) (catalytic conversion of DMDF acid into a compound of formula (I), wherein R, R1, R2 = CH3) The reactor was filled with 50 mm glass wool, and acidic ion exchanger DOWEX 50WX4 (= catalyst) was added. Methanol was then pumped through the catalyst bed until the solvent was colorless. Various reaction mixture compositions in methanol were pumped through the catalyst bed at 21°C, with specific residence times given in Table 3. Samples were taken after a certain time. The starting solution and samples were analyzed by qNMR. The results in Table 3 below clearly show that a downstream processing step of electrolysis of the mixture is required before the reaction mixture (= DMDF mainly in methanol) can react further in step (ii).

[0102] Table 3

Claims

1. A method for producing compounds of formula (I), ， Wherein R, R1, and R2 are independently straight-chain or branched C1-C6 alkyl groups, In the first step (step (i)), the compound of formula (II) in the Z-form is electrochemically reacted with at least one monohydric alcohol of formula (IV). ROH (IV), Where R has the same meaning as in the compound of formula (I), Then, In the second step (step (ii)), the reaction product of step (i) is a compound of formula (III), which reacts in the presence of a catalyst and at least one alcohol of formula (Va) and / or formula (Vb). Where R has the same meaning as in the compound of formula (I), R1-OH (Va) R2-OH (Vb), in R1 is a straight-chain or branched C1-C6 alkyl group, and R2 is a straight-chain or branched C1-C6 alkyl group. Its features are, After step (i) and before step (ii), The reaction mixture undergoes at least one nanofiltration step, followed by at least one pervaporation step.

2. The method according to claim 1, wherein R is -CH3 or -CH2CH3, and R1 is -CH3 or -CH2CH3, and R1 is -CH3 or -CH2CH3.

3. The method according to claim 1, wherein R, R1, and R2 are -CH3.

4. The method according to any one of the preceding claims, wherein The reaction in step (i) is carried out in a non-aqueous medium, wherein water may be present in such a medium at a weight of less than 50% based on the total weight of the non-aqueous medium.

5. The method according to any one of the preceding claims, wherein The reaction in step (i) occurs in at least one straight-chain or branched C1-C solvent. 10 The process is carried out in alcohols, preferably in at least one straight-chain or branched C1-C6 alcohol.

6. The method according to any one of the preceding claims, wherein The flow rate in step (i) is from 10 mL / min to 1000 mL / min.

7. The method according to any one of the preceding claims, wherein The electrochemical process in step (i) is carried out in the presence of at least one electrolyte selected from the group consisting of HCl, H2SO4, Na2SO4, NaCl, sodium dodecyl sulfate, methyltributylmethylammonium sulfate, triethylammonium bisulfate, tetrabutylammonium bisulfate, tetramethylammonium bisulfate, tetrabutylammonium acetate (NBu4OAc), tetrabutylammonium sulfate, tetrabutylammonium hexafluorophosphate, tetrabutylammonium tetrafluoroborate, methanesulfonic acid, ammonium bisulfate, tetrabutylphosphine methanesulfonate, 1-methylimidazolium hydrogen sulfate, tetrabutylammonium perchlorate, and LiClO4.

8. The method according to any one of the preceding claims, wherein The at least one nanofiltration step is performed using a polymer membrane.

9. The method according to claim 8, wherein The membrane has a molecular weight cutoff between 100 and 1000 Daltons.

10. The method according to any one of the preceding claims, wherein the at least one nanofiltration step is performed at a pressure between 1 and 60 bar.

11. The method according to any one of the preceding claims, wherein the at least one nanofiltration step is performed at a temperature between 15 and 70 degrees Celsius.

12. The method according to any one of the preceding claims, wherein the at least one pervaporation step is performed using a polymer membrane, preferably using a polyvinyl alcohol-based membrane.

13. The method according to any one of the preceding claims, wherein The pervaporation is carried out at a pressure of 1-20 bar.

14. The method according to any one of the preceding claims, The alcohol used is a mixture of alcohols or a pure alcohol, wherein R1 and R2 are the same part, preferably wherein the alcohol is a pure alcohol, wherein R1 and R2 are the same part.

15. The method according to any one of the preceding claims, wherein the catalyst in step (ii) is an acidic ion exchanger.

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