AN ELECTROCHEMICAL METHOD FOR PREPARING VANILLIN OR ITS DERIVATIVES

Abstract

The present invention relates to an electrochemical method for preparing vanillin or its derivatives in the presence of a mediator. The mediator can be recycled and reused and therefore no salt is formed by the end of the reaction, which makes the method more environmental-friendly. Furthermore, lower potentials are needed when the mediator is used by comparing to prior arts.

Claims

1. An electrochemical method for converting a compound of formula (I) to a compound of formula (II) in the presence of a solvent and a compound generating a mediator in reduced form in the solvent, ##STR00002## wherein: M.sup.P+ is a cation selected from group consisting of H.sup.+, NH.sub.4.sup.+ and metal cation; p is the valence of M; R.sup.1, R.sup.2, R.sup.3 and R.sup.4, independently from each other, are selected from the group consisting of: a hydrogen atom, an alkyl group, an alkoxy group, a hydroxyl group, a halogen atom, a haloalkyl group and a perhaloalkyl group; R.sup.5 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an aryl group or an aralkyl group.

2. The method according to claim 1, wherein R.sup.1 or R.sup.3 is an alkoxy group.

3. The method according to claim 2, wherein R.sup.1 or R.sup.3 is selected from the group consisting of methoxy, ethoxy, propoxy and butoxy and R.sup.2 or R.sup.4 is a hydrogen atom.

4. The method according to claim 1, wherein R.sup.5 is a hydrogen atom or an alkyl group.

5. The method according to claim 1, wherein the compound of formula (I) is 4-hydroxy-3-methoxy mandelic acid or 4-hydroxy-3-ethoxy mandelic acid.

6. The method according to claim 1, wherein the compound generating a mediator in reduced form in the solvent is selected from the group consisting of alkali metal bromides, alkali metal chlorides, alkali metal iodides, ammonium bromide, iron salts, cerium salts, manganese salts, copper salts, cobalt salts and chromium salts.

7. An electrochemical method for converting a compound of formula (I) as defined in claim 1 to a compound of formula (II) as defined in claim 1 comprising following steps: (i) dissolving a compound generating a mediator in reduced form in a solvent to obtain a solution; (ii) adding the solution obtained at step(i) to an electrochemical reactor; (iii) passing current to the electrochemical reactor to oxidize the mediator in reduced form to a mediator in oxidized form; (iv) contacting the compound of formula (I) with the mediator in oxidized form obtained at step (iii) to produce the compound of formula (II).

8. The method according to claim 7, wherein in step(i), the concentration of the compound generating a mediator in reduced form in the solution is in the range of 0.05 M to 2 M.

9. The method according to claim 7, wherein in step(iii) and (iv), the reaction temperature is from 0° C. to 100° C..

10. The method according to claim 7, wherein the molar ratio of the compound of formula (I) in step(iv) to the compound generating a mediator in reduced form in step(i) is equal to or higher than 1.

11. An electrochemical method for converting a compound of formula (I) as defined in claim 1 to a compound of formula (II) as defined in claim 1 in an electrochemical reactor comprising both an anode and a cathode, this method comprising the following steps: a) dissolving the compound of formula (I) and a compound generating a mediator in reduced form in a solvent to obtain Solution A; b) dissolving a compound generating a mediator in reduced form in a solvent to obtain Solution B; c) adding Solution A to the compartment having the anode and Solution B to the compartment having the cathode; d) passing current to the reactor to produce the compound of formula (II).

12. The method according to claim 11, wherein in step a), the molar ratio of the compound of formula (I) to the compound generating a mediator in reduced form is equal to or higher than 1.

13. The method according to claim 11, wherein the concentration of the compound generating a mediator in reduced form in Solution A of step a) or in Solution B of step b) is in the range of 0.01 M to 1 M.

14. The method according to claim 11, wherein in step a), the concentration of the compound of formula (I) in Solution A is in the range of 0.1 M to 1 M.

15. The method according to claim 11, wherein in step d), the reaction temperature is from 0° C. to 100° C..

16. The method according to claim 8, wherein in step(i), the concentration of the compound generating a mediator in reduced form in the solution is in the range of 0.1 M to 0.5 M.

17. The method according to claim 9, wherein in step(iii) and (iv), the reaction temperature is from 10° C. to 30° C.

18. The method according to claim 10, wherein the molar ratio of the compound of formula (I) in step(iv) to the compound generating a mediator in reduced form in step(i) is from 1.5 to 5.0.

Description

DETAILS OF THE INVENTION

[0023] As used herein, “mediator” is a redox substance that mediates electron transfer. In the present invention, this substance acts as electron shuttles between the oxidizing electrode and the compound of formula (I). The mediator is not particularly limited as long as it can shoulder the responsibility for transferring the electron between the oxidizing electrode and the compound of formula (I).

[0024] Examples of the compound generating a mediator in reduced form in the solvent are: [0025] Alkali metal bromides, such as lithium bromide (LiBr), sodium bromide (NaBr) and potassium bromide (KBr); [0026] Alkali metal chlorides, such as lithium chloride (LiCl), sodium chloride (NaCl) and potassium chloride (KCl); [0027] Alkali metal iodides, such as lithium iodide (LiI), sodium iodide (NaI) and potassium iodide (KI); [0028] Ammonium bromide (NH.sub.4Br); [0029] Iron salts, such as iron(II) sulphate (FeSO.sub.4), iron(II) bromide (FeBr.sub.2), iron(II) chloride (FeCl.sub.2), iron(II) iodide (FeI.sub.2), iron(II)nitrite (Fe(NO.sub.3).sub.2), iron(II) acetate ((C.sub.2H.sub.3O.sub.2).sub.2Fe), potassium ferricyanide (II) K.sub.4[Fe(CN).sub.6] and ferrocene; [0030] Cerium salts, such as cerium(III) sulfate Ce.sub.2(SO.sub.4).sub.3; [0031] Manganese salts, such as manganese(II) sulfate (MnSO.sub.4); [0032] Copper salts, such as copper(II) sulfate (CuSO.sub.4), copper(II) bromide (CuBr.sub.2), copper(II) chloride (CuCl.sub.2), copper(II) iodide (CuI2), copper(II) nitrite (Cu(NO.sub.3).sub.2) and copper(II) acetate ((C.sub.2H.sub.3O.sub.2)2Cu); [0033] Cobalt salts, such as cobalt(II) sulfate (CoSO.sub.4), cobalt(II) bromide (CoBr.sub.2), cobalt(II) chloride (CoCl2), cobalt(II) iodide (CoI.sub.2), cobalt(II) nitrite (Co((NO.sub.3).sub.2) and cobalt(II) acetate ((C.sub.2H.sub.3O.sub.2).sub.2Co); [0034] Chromium salts, such as chromium(III) sulfate (Cr2(SO.sub.4).sub.3), chromium (III) bromide (CrBr.sub.3), chromium(III) chloride (CrCl.sub.3), chromium(III) iodide (CrI.sub.3), chromium(III) nitrite (Cr(NO.sub.3).sub.3) and chromium(III) acetate((C.sub.2H.sub.3O.sub.2).sub.3Cr).

[0035] In some embodiments, sodium bromide (NaBr) or ammonium bromide (NH.sub.4Br) can be preferably used.

[0036] In some embodiments, environmental-friendly compound such as iron salts can be preferably used. Among all iron salts, iron(II) sulphate (FeSO.sub.4) is more preferable.

[0037] In the method according to the present invention, a mediator in reduced form is obtained when the compound above mentioned is dissolved in a solvent. It shall be understood by the skilled person that the mediator in reduced form is oxidized at the anode so as to obtain a mediator in oxidized form when the current is passed to the reactor. The mediator in oxidized form then oxidizes the compound of formula (I) and simultaneously forms a mediator in reduced form, which can be same as or different from the mediator reduced form obtained when the compound is dissolved.

[0038] Examples of the mediator in reduced form are: [0039] Halogen ions, such as Br.sup.−, Cl.sup.− and I.sup.−; [0040] Metal ions, such as Fe.sup.2+, Fe(CN).sub.6.sup.4−, Mn.sup.2+, MnO.sub.4.sup.2−, Ce.sup.3+, Cr.sup.3+ and Co.sup.2+.

[0041] Examples of the mediator in oxidized form are: [0042] Halogen ions, such as hypobromite (OBr.sup.−), hypochloride (OCl.sup.−) and hypoiodite (OI.sup.−); [0043] Metal ions, such as Fe.sup.3+, Fe(CN).sub.6.sup.3−, MnO.sub.4.sup.2−, MnO.sub.4.sup.2−, Ce.sup.4+, HCrO.sub.4.sup.− and Co.sup.3+.

[0044] As defined above, MP+can be a metal cation. Preferably, p is 1 or 2. Examples of the metal cation are: K.sup.+, Li.sup.+, Na.sup.+ and Mg.sup.2+.

[0045] In some preferred embodiments, M.sup.P+ is H.sup.+.

[0046] As defined above, R.sup.1, R.sup.2, R.sup.3 and R.sup.4, independently from each other, are selected from the group consisting of: a hydrogen atom, an alkyl group, an alkoxy group, a hydroxyl group, a halogen atom, a haloalkyl group and a perhaloalkyl group.

[0047] In some embodiments, R.sup.1, R.sup.2, R.sup.3 and R.sup.4, independently from one another, may be a hydrogen atom or a C.sub.1-C.sub.6 alkyl group. More preferably, R.sup.1, R.sup.2, R.sup.3 and R.sup.4, independently from one another, are selected from the group consisting of: a hydrogen atom, methyl, ethyl, propyl and isopropyl.

[0048] In some embodiments, R.sup.1 or R.sup.3 may be an alkoxy group, which is selected from the group consisting of methoxy, ethoxy, propoxy and butoxy. R.sup.2 or R.sup.4 may be a hydrogen atom.

[0049] According to a specific aspect of the present invention, R.sup.5 is a hydrogen atom or an alkyl group.

[0050] The compound of formula (I) can be notably 4-hydroxy-3-methoxy mandelic acid or 4-hydroxy-3-ethoxy mandelic acid.

[0051] The compound of formula (II) can be notably 4-hydroxy-3 -methoxybenzaldehyde or 4-hydroxy-3-ethoxybenzaldehyde.

[0052] It is understood that the solvent shall have good solubility for both the compound of formula (I) and the compound generating the mediator in reduced form so that they can have sufficient contact in the solution. Such solvent can be alcohol, water or their combination. Preferably, the solvent is water.

[0053] pH value of the solution comprising the compound of formula (I), and the compound generating a mediator in reduced form depends on the mediator and is optionally adjusted by the skilled person. For example, pH value of the solution comprising compound of formula (I) and an iron salt shall be adjusted to below 4 and preferably below 3 to prevent the formation of iron(II)/(III) hydroxide. pH value of the solution comprising compound of formula (I) and an alkali metal bromide shall be adjusted to an acidic or slight basic solution to prevent the formation of the toxic Bra gas.

[0054] The method according to the present invention is carried out in such a preferred reactor comprising both an anode and a cathode.

[0055] The anode and/or the cathode preferably comprises a catalyst. The catalyst for the anode or the cathode may comprise metal element, which can be in the form of elemental metal, metal alloy, metal oxide or metal complex.

[0056] The anode catalyst may preferably comprise element selected from the group consisting of elements of Groups IIIA, IVA, VA of Periodic Table and Transition metals.

[0057] As used herein, metals of group IB, IIB, IIIB, IVB, VB, VIB, VIIB and VIIIB are often referred to as transition metals. This group comprises the elements with atomic number 21 to 30 (Sc to Zn), 39 to 48 (Y to Cd), 72 to 80 (Hf to Hg) and 104 to 112 (Rf to Cn).

[0058] Examples of the anode catalyst are notably: [0059] (i) Elemental metal comprise element selected from the group consisting of Pd, Pt, Ru, Au, Rh, Ir, Bi, Sn, B and any combination thereof. [0060] (ii) Metal alloy, such as Pd-Au, Pd-B and Pt-Ru.

[0061] Preferably, the anode catalyst is Pt.

[0062] The cathode catalyst may preferably comprise element selected from the group consisting of elements of Groups IA, IIA, IIIA, IVA, VA, VIA, VIIA of Periodic Table, Transition metals and Lanthanides.

[0063] Examples of the cathode catalyst are notably: [0064] Elemental metal comprise element selected from the group consisting of Pt, Ni, Cu, C and any combination thereof.

[0065] Preferably, the cathode catalyst is Ni or Cu and more preferably Cu.

[0066] The catalyst for the anode or the cathode mention above can be loaded on a support. The support is not particularly limited. Typical examples of support are carbon, alumina and silica.

[0067] In one embodiment, the anode or the cathode may comprise a catalyst mentioned above and a substrate.

[0068] Preferably, the anode and the cathode can be made with porous substrate structures.

[0069] The anode substrates can include, for example, stainless steel net, nickel foam, sintered nickel powder, etched aluminum-nickel mixtures, carbon fibers, and carbon cloth. Preferably, carbon materials and stainless steel are used as an anode substrate.

[0070] The cathode substrates can include stainless steel, nickel foam, sintered nickel powder, etched aluminum-nickel mixtures, metal screens, carbon fibers, and carbon cloth.

[0071] Methods for applying the anode catalyst to the anode substrate, and the cathode catalyst to the cathode substrate include, for example, spreading, wet spraying, powder deposition, electro- deposition, evaporative deposition, dry spraying, decaling, painting, sputtering, low pressure vapor deposition, electrochemical vapor deposition, tape casting, screen printing, hot pressing and other methods.

[0072] When substrates are used, preferred range of the catalyst loading may be comprised between 0.01 mg/cm.sup.−2 and 500 mg/cm.sup.−2. More preferably, the catalyst loading amount may be comprised between 1 mg/cm.sup.−2 and 20 mg/cm.sup.−2.

[0073] In a preferred embodiment, the electrochemical reactor used according to the invention has two independent compartments. The anode and the cathode reside in these two compartments separately. A membrane can be placed between the two compartments. Said membrane can be neutral or ion-exchange membrane. Preferably, the membrane is a nafion (a sulfonated tetrafluoroethylene based fluoropolymer-copolymer) cation exchange membrane.

[0074] Advantageously, the distance between the anode and the cathode is in the range of 1 mm to 10 cm and preferably 3 mm to 1 cm.

[0075] In one embodiment, the method according to the present invention comprises following steps: [0076] (i) dissolving the compound generating a mediator in reduced form in the solvent to obtain a solution; [0077] (ii) adding the solution obtained at step(i) to an electrochemical reactor; [0078] (iii) passing current to the electrochemical reactor to oxidize the mediator in reduced form to a mediator in oxidized form; [0079] (iv) contacting the compound of formula (I) with the mediator in oxidized form obtained at step (iii) to produce the compound of formula (II).

[0080] Step(i)

[0081] The concentration of the compound generating a mediator in reduced form in the solution can be in the range of 0.05 M to 2 M and preferably 0.1 M to 0.5 M.

[0082] Step(iii)

[0083] Preferably, the reaction temperature can be from 0° C. to 100° C. and more preferably from 10° C. to 30° C. and most preferably room temperature.

[0084] According to the present invention, room temperature is between 15° C. and 25° C.

[0085] Preferably, the reaction can be run for 1 h to 144 h and more preferably 2 h to 50 h.

[0086] Preferably, the reaction can be run at a current density ranging from 0.1 mA/cm.sup.2 to 100 mA/cm.sup.2 and more preferably from 0.5 mA/cm.sup.2 to 15 mA/cm.sup.2.

[0087] Preferably, the reaction can be run at a potential ranging from 0.0001 V to 10 V and more preferably from 1.5 V to 4 V.

[0088] Step(iv)

[0089] The molar ratio of the compound of formula (I) in this step to the compound generating a mediator in reduced form in step (i) can be equal to or higher than 1 and preferably from 1 to 10 and more preferably from 1.5 to 5.0.

[0090] Preferably, the reaction temperature can be from 0° C. to 100° C. and more preferably from 10° C. to 30° C. and most preferably room temperature.

[0091] According to the present invention, room temperature is between 15° C. and 25° C.

[0092] The skilled person will use the proper reaction time based on the reaction parameters above mentioned.

[0093] In another embodiment, the method according to the present invention carried out in an electrochemical reactor comprising both an anode and a cathode has following steps: [0094] a) dissolving the compound of formula (I) and the compound generating a mediator in reduced form in the solvent to obtain Solution A; [0095] b) dissolving the compound generating a mediator in reduced form in the solvent to obtain Solution B; [0096] c) adding Solution A to the compartment having the anode and Solution B to the compartment having the cathode; [0097] d) passing current to the reactor to produce the compound of formula (II).

[0098] Step a)

[0099] The molar ratio of the compound of formula (I) to the compound generating a mediator in reduced form can be equal to or higher than 1 and preferably from 1 to 10 and more preferably from 1.5 to 5.0.

[0100] The concentration of the compound generating a mediator in reduced form in Solution A can be in the range of 0.01 M to 1 M and preferably 0.05 M to 0.2 M.

[0101] The concentration of the compound of formula (I) in Solution A can be in the range of 0.1 M to 1 M and preferably 0.1 M to 0.3 M.

[0102] Step b)

[0103] The concentration of the compound generating a mediator in reduced form in Solution B can be in the range of 0.01 M to 1 M and preferably 0.05 M to 0.2 M.

[0104] As can be understood by one skilled in the art, the sequence of step a) and step b) may be reversed, or performed simultaneously.

[0105] Step d)

[0106] Preferably, the reaction temperature in this embodiment can be from 0° C. to 100° C. and more preferably from 10° C. to 30° C. and most preferably room temperature.

[0107] Preferably, the reaction in this embodiment can be run at a current density ranging from 0.1 mA/cm.sup.2 to 100 mA/cm.sup.2 and more preferably 1 mA/cm.sup.2 to 15 mA/cm.sup.2.

[0108] Preferably, the reaction can be run at a potential ranging from 0.0001 V to 10 V and more preferably 1.5 V to 4 V.

[0109] Preferably, the reaction can be run for 1 h to 144 h.

[0110] The following examples are included to illustrate embodiments of the invention. Needless to say, the invention is not limited to described examples.

EXPERIMENTAL PART

[0111] Materials [0112] Sodium bromide: CAS No 7647-15-6 from Sigma-Aldrich [0113] Iron(II) sulfate heptahydrate : CAS No 7782-63-0 from Sigma-Aldrich [0114] 4-Hydroxy-3-methoxymandelic acid (vanillylmandelic acid) : CAS No 55-10-7 from Sigma-Aldrich

Example 1

[0115] Ex-situ Synthesis of Mediator

[0116] In order to prove that vanillin is formed by the mediator and not by electrochemistry, therefore in a first step BrO— will be formed by electrochemical oxidation of Br- in an H-Cell setup by electrochemistry. In a second step this solution will be added to 4-hydroxy-3-methoxy mandelic acid. Stirred for 4h. [0117] 100 ml of 0.15 M NaBr aqueous solution is prepared including 1 ml of 1 M NaOH to achieve a slightly basic medium (total concentration=0.01M, pH between 7 and 8). [0118] As reactor an 80 ml H-cell is used. Both sides are filled with 50 ml of the above prepared solution. The membrane is a sulfone based cation exchange membrane (Nafion, M=1100, thickness=0.07 in). In the anode chamber a circular Pt mesh is used as working electrode. (Diameter=2 cm, height=0.1 cm, surface area=3.14 cm.sup.2). In the cathode chamber a copper plate (1 cm×1.5 cm, thickness=2 mm) is used as counter electrode. Prior to use the electrodes are cleaned. The Pt is cleaned with ethanol in ultrasonic bath for 15 min, rinsed with ethyl acetate and air dried. The Cu electrode is placed for 15 min in 2M HC1 solution in ultrasonic bath, then rinsed with deionized water and placed another 15 min in the ultrasonic bath in ethanol. The Cu plate is rinsed with ethyl acetate and air dried. [0119] The reaction is run for 20 h at a current density of 6.4 mA/cm.sup.2. [0120] In the second step, 0.86 mmol vanillylmandelic acid is weight and placed in a 10 ml beaker with stirr bar. In total 6 x 1 ml (equimolar) of the BrO— solution is dropped into the vessel while stirring. After slow addition of 1 ml 5 minutes are waited before the next addition. After 6 ml was added the reaction is allowed to stir overnight. The reaction solution has a strong vanillin smell. A precipitate is formed which is separated by centrifuging. The liquid phase is extracted with ethyl acetate. As well as the product of the organic phases as the solid precipitate are analyzed by NMR using DMSO. The estimated results show a total conversion of about 53%. The selectivity of the solid phase shows approximately 30% vanillin, 70% bisvanillin The liquid phase showed 13% vanillin, 17% vanillic acid , 1% bisvanillin, 69% other.

Example 2

[0121] Electrochemical decarboxylation of 4-hydroxy-3-methoxy mandelic acid with sodium bromide.

[0122] A 20 ml H-cell with a nafion cation exchange membrane is used as reactor. After the membrane is placed between the cells, water is filled in both sides in order to check the sealing. The anode side is equipped with a Pt mesh as working electrode: diameter=1 cm, height=2 cm. Surface area=6.3 cm.sup.2. The cathode side uses a 200 ppi Cu mesh as counter electrode. It is bent into cylindrical shape: length=4 cm, height=2 cm, surface area=8 cm.sup.2. The system is not stirred and no reference electrode is used. [0123] NaBr (0.1672 g, 0.1 M) and mandelic acid (0.7109 g, 0.3 M) is dissolved in 12 ml water and transferred into the anode chamber. The pH resulted in about 2. The cathode solution consists of NaBr (0.1644 g, 0.1 M) in 12 ml water. [0124] For 144 h current with a current density of 0.5 mA/cm.sup.2 is applied at the anode. [0125] Work-up: the anode solution is 5 times extracted with 20 ml dichloromethane, dried over NaSO.sub.4 and decanted. CH.sub.2Cl.sub.2 is removed in vacuum. [0126] Following samples are taken for NMR: reaction solution before work-up, water phase after extraction, precipitate on anode, and organic phase. In addition HPLC is performed. [0127] The HPLC show about 6 major products and the reactant. Vanillin could be clearly identified at a retention time of 12.394 min. The mandelic acid derivative is present at about 3.635 min. It seems that also dimer and trimer of vanillin is present. There are several unknown peaks which could be side products where the methoxy group at the aromatic ring is substituted by hydroxy group due to the acidic pH in the solution. Vanillic acid was not observed. Conversion was about 37% with a vanillin selectivity of 45%.

Example 3

[0128] Electrochemical decarboxylation of 4-hydroxy-3-methoxy mandelic acid with iron sulfate [0129] A 50 ml H-cell with a nafion cation exchange membrane is used as reactor. After the membrane is placed between the cells, water is filled in both sides in order to check the sealing. The anode side is equipped with a Pt mesh as working electrode: diameter=1 cm, height=2 cm. Surface area=6.3 cm.sup.2. The cathode side uses a 200 ppi Cu mesh as counter electrode. It is bent into cylindrical shape: length=5 cm, height=2 cm, surface area=10 cm.sup.2. The system is not stirred and no reference electrode is used. [0130] FeSO.sub.4 (0.8361 g, 0.1 M) and mandelic acid derivative (1.7839 g, 0.3 M) is dissolved in 20 ml water and 10 ml 1M H.sub.2SO.sub.4 and transferred into the anode chamber. The pH resulted in about 0. The cathode solution consists of 0.1 M FeSO.sub.4 (0.8356g) solution in 10m ml 1M H.sub.2SO.sub.4 and 20 ml water. [0131] For 144 h current with a current density of 10 mA/cm.sup.2 is applied at the anode. [0132] Work-up: the anode solution is 5 times extracted with 20 ml dichloromethane, dried over NaSO.sub.4 and decanted. CH.sub.2Cl.sub.2 is removed in vacuum. [0133] Following samples are taken for NMR: reaction solution before work-up, water phase after extraction, precipitate on anode, and organic phase. [0134] After 2.5 h 15% of mandelic acid was converted. Next to several unknown side products vanillin and dihydroxy benzaldehyde was formed with selectivities of 17% and 16% respectively