Systems and processes for anthraquinone functionalization

Abstract

To realize synthetic functionalization of anthraquinone molecules substituted with at least one hydroxyl group or amino group.SOLUTION: According to part of embodiments of the present invention, synthetic functionalization of anthraquinone molecules occurs not chemically but electrochemically by using a divided electrolytic tank.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application was filed as a PCT International Patent Application on June 9, 2022, and claims the benefit of and priority to U.S. Provisional Application No. 63 / 215,079, filed on June 25, 2021, the entire disclosure of which is incorporated herein by reference in its entirety. The present invention relates generally to synthetic organic chemical processes. More specifically, the present invention relates to the synthetic functionalization of anthraquinone molecules substituted with at least one hydroxyl or amino group. Statement Regarding Federally Sponsored Research Certain aspects of this invention were made with government support from the U.S. Department of Energy under Award No. DE-AC05-76RL01830 through PNNL Subcontract 535264. The government has certain rights in this invention. [Background technology]

[0002] The Marschalk reaction is the reaction of a hydroxyl- or amino-substituted anthraquinone with an aldehyde in the presence of sodium dithionite, introducing an α-hydroxyalkyl functional group at the ortho position of the hydroxyl or amine substituent on the starting molecule. See L.-M. Zhao, F.-Y. Ma, H.-S. Jin, J. Ma, H. Wang, C.-Z. Fu, European Journal of Organic Chemistry, 2013, 7193-7199. Under certain conditions, dehydroxylation of the α-hydroxyalkyl functional group follows, leaving a methylene (-CH2-) linker between the anthraquinone core and the remaining new functional group. This reaction works with a variety of aldehydes, including formaldehyde, acetaldehyde, benzaldehyde, and glyoxylic acid. See, for example, K. Krohn, Angewandte Chemie International Edition 1979, 18, 621-622. The reaction can be intermolecular or intramolecular. See F. Suzuki, S. Trenbeath, RD Gleim, CJ Sih, Journal of the American Chemical Society 1978, 100, 2272-2273. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] U.S. Patent No. 2,941,865 [Non-patent literature]

[0004] [Non-Patent Document 1] European Journal of Organic Chemistry,2013,7193-7199 [Non-patent document 2] Angewandte Chemie International Edition 1979,18,621-622 [Non-patent document 3] Journal of the American Chemical Society 1978,100,2272-2273 [Non-patent document 4] Science 2015,349,1529-1532 Summary of the Invention [Problem to be solved by the invention]

[0005] In all reported examples of the (α-hydroxy)alkylation or alkylation of hydroxyl- or amino-substituted anthraquinones, the reducing agent used is sodium dithionite. The same reaction can be carried out at lower cost by replacing sodium dithionite with another, less expensive reducing agent. [Brief explanation of the drawings]

[0006] [Figure 1] 1 shows a synthetic scheme for (α-hydroxy)alkylation or alkylation of a substituted anthraquinone starting material by catalytic reduction of the substituted anthraquinone starting material with hydrogen gas, according to certain embodiments. [Figure 2] 1 shows a synthetic scheme for the (α-hydroxy)alkylation or alkylation of a substituted anthraquinone starting material by electrochemical reduction of the substituted anthraquinone starting material, according to certain embodiments. [Figure 3] 1 shows an electrolytic cell for effecting (α-hydroxy)alkylation or alkylation of a substituted anthraquinone starting material by electrochemical reduction of the substituted anthraquinone starting material, according to certain embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0007] The Marschalk reaction mechanism begins with the reduction of the 9,10-anthraquinone core of a substituted anthraquinone starting material to a 9,10-dihydroxyanthracene core. This reduced starting material then reacts with an aldehyde to form a carbon-carbon bond.

[0008] It is known that 9,10-anthraquinone can be easily reduced to the corresponding 9,10-dihydroxyanthracene using other reactants such as hydrogen gas, optionally in the presence of a catalyst such as palladium supported on a carbon substrate. See G. Max, L. Emile, U.S. Pat. No. 2,941,865 (filed October 16, 1956). Alternatively, the reduction can be achieved electrochemically, such as in a half-cell of a flow battery. See K. Lin, Q. Chen, M.R. Gerhardt, L. Tong, S.B. Kim, L. Eisenach, A.W. Valle, D. Hardee, R.G. Gordon, M.J.A. Ziz, M.P. Marshak, Science 2015, 349, 1529-1532.

[0009] However, the use of reducing agents other than sodium dithionite in the Marschalk reaction is unknown. The present invention features the synthesis of anthraquinone derivatives via a process similar to the classical Marschalk reaction, but using reducing agents other than sodium dithionite or other dithionites.

[0010] In one embodiment of the present invention, summarized in Figure 1, a substituted anthraquinone starting material, an aldehyde, a base, an optional solvent, and an optional catalyst are mixed in a reaction vessel exposed to an atmosphere containing hydrogen gas. The reaction may be heated, cooled, or held at different temperatures throughout the reaction time. Depending on the reaction temperature, either the (α-hydroxy) alkylated product or the dehydroxylated alkylated product will be favored. After a predetermined time, an oxidizing agent is introduced to the reaction mixture. After a further predetermined time, the reaction product is isolated from the reaction mixture and, optionally, purified by conventional means familiar to those skilled in the art (e.g., precipitation, filtration, distillation, sublimation, recrystallization, solvent extraction, washing, chromatography, centrifugation).

[0011] In some embodiments of the present invention, the substituted anthraquinone starting material comprises Formula I: [ka]

[0012] wherein X is selected from the group consisting of a hydroxy group or an amino group at the 1-position, and the 2-position of the anthraquinone is unsubstituted (i.e., a carbon bonded to a hydrogen). Those skilled in the art will understand that other substituents present on the substituted anthraquinone starting material may alter the positional numbering of the aforementioned hydroxy or amino group, as well as the positional numbering of the unsubstituted carbon atom ortho to it. However, the positional numbering will not affect the general reactivity, but will only affect the relative positioning of the hydroxy group and its adjacent unsubstituted carbon atom on the substituted anthraquinone. In some embodiments of the present invention, an aldehyde is covalently bonded to an anthraquinone derivative, and the reaction may proceed intramolecularly or under certain conditions to form a dimer, a cyclamer, or an oligomeric or polymeric chain.

[0013] In some embodiments of the present invention, the base is selected from the group consisting of inorganic hydroxides, metal alkoxides, amines, or amidines, or mixtures thereof. In certain embodiments of the present invention, the base is an alkali metal hydroxide (e.g., sodium hydroxide or potassium hydroxide). In other embodiments of the present invention, the base is a metal alkoxide or alkali metal alkoxide (e.g., sodium methoxide or potassium tert-butoxide). In other embodiments of the present invention, the base is an amine or trialkylamine (e.g., triethylamine or diisopropylethylamine). In other embodiments, the base is an amidine, wherein the amidine is a non-nucleophilic base (e.g., 1,8-diazabicycloundec-7-ene (DBU) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)).

[0014] In general, most aldehydes can undergo a reaction similar to the traditional Marschalk reaction described in the above-mentioned literature. In some embodiments of the reaction, the aldehyde is a water-soluble aldehyde (e.g., formaldehyde or acetaldehyde). In other embodiments of the reaction, the aldehyde is an organic compound (e.g., benzaldehyde) that is poorly soluble or insoluble in water but soluble in organic solvents. In even more embodiments of the present invention, the aldehyde (e.g., glyoxylic acid) contains an acidic group that confers solubility when mixed with a base.

[0015] In some embodiments of the present invention, aldehydes can reversibly interconvert between a form with a free aldehyde group and a form in which a molecule of water or alcohol is added to the aldehyde group, thus forming a gem-diol or hemiacetal, respectively. In a further aspect of the present invention, the alcohol group is located on the same molecule as the aldehyde, and the reversible addition occurs intramolecularly. In another aspect of the present invention, the aldehyde functionality forms an open-chain form upon ring opening during the course of the reaction. Examples of such "transient" aldehydes are reducing sugars, including, but not limited to, glucose, galactose, fructose, mannose, xylose, arabinose, glyceraldehyde, lactose, cellobiose, and maltose. These reducing sugars can exist as either D- or L-enantiomers, or a mixture of the two, or a racemic mixture. It will be understood by those skilled in the art that any reducing sugar may be used in the embodiments described herein. Other embodiments of the reaction may use a non-reducing sugar, which is then converted to an aldehyde-containing reducing sugar during the course of the reaction. An example of such a non-reducing sugar is fructose, which can be converted to either glucose or mannose, both of which are reducing sugars.

[0016] In some embodiments of the present invention, the base and / or aldehyde act as the solvent. In other embodiments of the present invention, the solvent is a separate species, such as water, methanol, ethanol, isopropanol, 1,4-dioxane, N,N-dimethylformamide, etc. In other embodiments of the present invention, the solvent comprises two or more solvents, such as a water-ethanol mixture, a methanol-N,N-dimethylformamide mixture, a water-1,4-dioxane mixture, etc. It will be understood by those skilled in the art that any polar, protic or aprotic solvent and mixtures thereof may be used in the embodiments described herein.

[0017] In some embodiments of the present invention, the optional catalyst is a catalyst for catalytic hydrogenation or a pre-catalyst that is converted into an active catalyst for catalytic hydrogenation during the course of the reaction. The catalyst may optionally be supported on a substrate. Examples of catalysts include, but are not limited to, nickel on carbon, palladium on carbon, platinum on carbon, rhodium on carbon, palladium hydroxide, platinum black, platinum dioxide, Wilkinson's catalyst, Crabtree's catalyst, Shvo's catalyst, and the like.

[0018] In some embodiments of the present invention, the reaction atmosphere is composed partially or entirely of hydrogen. The reaction atmosphere may be at atmospheric pressure, subatmospheric pressure, or superatmospheric pressure.

[0019] In some embodiments of the present invention, the oxidizing agent is present in the gas phase and may be air, oxygen, ozone, or a mixture thereof. Alternatively, the oxidizing agent may be a liquid or in a solution phase (including, but not limited to, dimethyl sulfoxide or hydrogen peroxide). The oxidizing agent may be a solid, such as silver(I) oxide. Combinations of different oxidizing agents may also be used.

[0020] In some embodiments of the present invention, the catalyst is Raney nickel and hydrogen is already present on the surface of the catalyst and is not provided as a gas to the atmosphere of the reaction vessel.

[0021] In some embodiments of the present invention, the aldehyde is introduced only after the hydrogen has been vented from the reaction vessel, but before the reduced substituted anthraquinone starting material is reoxidized by the oxidizing agent.

[0022] In another embodiment of the invention, summarized as a chemical reaction in Figure 2 and illustrated in Figure 3, the reduction of the substituted anthraquinone starting material occurs electrochemically rather than chemically by using a split electrolytic cell 300. Split electrolytic cell 300 includes a first chamber 310 having a first electrode 311 separated from a second chamber 320 having a second electrode 321 by an ion-conducting membrane 330. Independently, an electrocatalyst may be present only at the first electrode 311, only at the second electrode 321, at both the first electrode 311 and the second electrode 321, or no electrocatalyst may be present at either the first electrode 311 or the second electrode 321.

[0023] A first fluid stream 312 containing the substituted anthraquinone starting material of Formula I, an aldehyde, a base, and an optional solvent flows into the first chamber of the electrolytic cell 310 through a first chamber inlet 313, causing the first fluid stream to contact the first electrode 311 and exit through a first chamber outlet 314. Simultaneously, a second fluid stream 322 flows into the second chamber of the electrolytic cell 320 through a second chamber inlet 323, causing the second fluid stream to contact the second electrode 321 and exit through a second chamber outlet 324. An electric potential 340 is applied to the two electrodes such that the first electrode is at a more negative potential relative to the second electrode. In some embodiments, the first electrode is the cathode and the second electrode is the anode.

[0024] As the first fluid stream 312 passes through the first electrode 311, it is electrochemically reduced. Similarly, as the second fluid stream 322 passes through the second electrode 321, it is electrochemically oxidized. The first fluid stream 312 can pass through the first chamber 310 of the split electrolyzer 300 only once, or the fluid exiting the first chamber outlet 314 can be recycled and flow back to the first chamber inlet 313 multiple times. Similarly, the second fluid stream 322 can pass through the second chamber 320 of the split electrolyzer 300 only once, or the fluid exiting the second chamber outlet 324 can be recycled and flow back to the second chamber inlet 323 multiple times. The split electrolyzer 300, the first fluid stream 312, and / or the second fluid stream 322 can be heated, cooled, or held at different temperatures throughout the reaction period. Depending on the reaction temperature, either the (α-hydroxy) alkylated product or the dehydroxylated alkylated product is favored.

[0025] After a predetermined time or a predetermined amount of charge has passed, the first fluid stream 312 can be treated in one of several ways, as described below, and the reaction product can then be isolated from the treated first fluid stream and, optionally, purified by conventional means well known to those skilled in the art. The threshold amount of charge to pass can be predetermined by determining the theoretical amount of charge required for the reaction to proceed to completion. In Figure 2, the anthraquinone starting material is reduced to a 9,10-dihydroxyanthracene derivative, which then requires two equivalents of electrons to react with an aldehyde to form an (α-hydroxy) alkylated intermediate. This intermediate then undergoes intramolecular disproportionation to produce an alkylated product and a reoxidized anthraquinone core, which can accept two more electrons. In this case, the threshold amount of charge is four equivalents relative to the amount of anthraquinone starting material originally present. If two equivalents of aldehyde react with one molecule of anthraquinone starting material, the theoretical amount of charge to pass is six equivalents. A larger threshold amount of charge can be set to account for process inefficiencies such as the effect of oxygen reoxidizing the reaction mixture, coulombic efficiency resulting from side reactions, etc. Conversely, if the (α-hydroxy)alkylated intermediate is actually the desired product, or if the (α-hydroxy)alkylated material is the starting material and the dehydroxylated alkylated material is the desired product, a smaller equivalent of charge (e.g., about 2 equivalents) can be used as the reaction endpoint.

[0026] Alternatively, if the alkylated (non-α-hydroxylated) product is the desired product and fewer and fewer 9,10-anthraquinone cores remain in the reaction mixture available to accept electrons toward the end of the reaction, a threshold voltage (when current is passed galvanostatically) or a threshold current or current density (when current is passed potentiostatically) can be used instead of a predetermined time or a predetermined amount of charge passed. This manifests as a sudden increase in voltage when current is passed galvanostatically, or a decrease in current when current is passed potentiostatically. To minimize the amount of potential side reactions, it is recommended to set an upper threshold voltage or a lower threshold current (or current density) above which the current stops. The threshold voltage can be defined as a fixed number (e.g., >0.5V / cell, >1.0V / cell, >1.5V / cell, >1.6V / cell, >1.7V / cell, >1.8V / cell, >1.9V / cell, >2.0V / cell, >2.1V / cell, >2.2V / cell, >2.3V / cell, >2.4V / cell, >2.5V / cell, etc.), or it can be defined as a percentage increase relative to the average voltage for the first certain number of equivalents of charge passed (e.g., >10% of the average voltage for the first equivalent of charge passed, >20% of the average voltage for the first 0.5 equivalents of charge passed, >30% of the average voltage for the first 0.5 equivalents of charge passed, >40% of the average voltage for the first 0.25 equivalents of charge passed, >50% of the average voltage for the first 0.1 equivalents of charge passed, and many such combinations thereof). For example, if the theoretical amount of charge that can pass is 4 equivalents, and the cell voltage is an average of 1.5 V above the first equivalent of charge passed, a threshold voltage of 30% above the onset voltage means that if current is applied galvanostatically, the current will cease when the voltage exceeds 1.95 V / cell. Similarly, the threshold current (or current density) can be expressed as a number (e.g., <10 A, <1 A, <0.1 A, <0.01 A, <10 mA / cm). 2 , <1mA / cm 2 , <0.1mA / cm 2 , <0.01A / cm 2etc.), or it can be defined as a percentage of the average current or current density for the first particular number of equivalents of charge passed (e.g., <10% of the average current or current density for the first equivalent of charge passed, <5% of the average current or current density for the first 0.5 equivalents of charge passed, <2% of the average current or current density for the first 0.5 equivalents of charge passed, <1% of the average current or current density for the first 0.2 equivalents of charge passed, <0.5% of the average current or current density for the first 0.25 equivalents, <0.2% of the average current or current density for the first 0.1 equivalents of charge passed, <0.1% of the average current or current density for the first 0.1 equivalents of charge passed, and many such combinations thereof). For example, if the theoretical amount of charge that can pass is 4 equivalents and the current density is 100 mA / cm2 for the first equivalent of charge passed, 2 If above, the threshold current density of <1% of the onset current density is 1 mA / cm when the current is applied potentiostatically. 2 In some embodiments, current is passed galvanostatically until the cell voltage reaches a certain threshold, such as 1.2V, 1.4V, 1.6V, 1.8V, etc., and then the cell voltage is maintained until the current or current density falls below a similarly designated threshold for constant voltage operation.

[0027] In some embodiments of the reaction, the substituted anthraquinone comprises Formula II: [ka]

[0028] wherein X is a hydroxyl or amino group. In some embodiments, X and X are the same. In other embodiments, X and X are different. Examples include 1,5-dihydroxyanthraquinone, 1,5-diaminoanthraquinone, 1-hydroxy-5-aminoanthraquinone, etc.

[0029] In another embodiment of the reaction, the substituted anthraquinone comprises formula III: [ka]

[0030] wherein X is a hydroxyl or amino group. In some embodiments, X and X are the same. In other embodiments, X and X are different. Examples include 1,8-dihydroxyanthraquinone, 1,8-diaminoanthraquinone, 1-hydroxy-8-aminoanthraquinone, etc. Anthraquinones of Formulas II and III containing two X substituents on separate aromatic rings of the same molecule, or two unsubstituted positions ortho to each X substituent, can be reacted with two equivalents of an aldehyde to form bis(α-hydroxy)alkylated or bis-alkylated products.

[0031] In another embodiment of the reaction, the substituted anthraquinone comprises formula IV: [ka]

[0032] wherein X is a hydroxyl or amino group. In some embodiments, X and X are the same. In some embodiments, X and X are different. Examples include 1,4-dihydroxyanthraquinone, 1,4-diaminoanthraquinone, 1-hydroxy-4-aminoanthraquinone, etc. Anthraquinones of Formulas II, III, and IV containing two X substituents on separate aromatic rings of the same molecule, or two unsubstituted positions ortho to each X substituent, can be reacted with two equivalents of an aldehyde to form bis(α-hydroxy)alkylated or bis-alkylated products.

[0033] In some embodiments of the present invention, the base is selected from the group consisting of inorganic hydroxides, metal alkoxides, amines, amidines, and mixtures thereof. In certain embodiments of the present invention, the base is an alkali metal hydroxide (e.g., sodium hydroxide or potassium hydroxide). In other embodiments of the present invention, the base is a metal alkoxide or alkali metal alkoxide (e.g., sodium methoxide or potassium tert-butoxide). In other embodiments of the present invention, the base is an amine or trialkylamine (e.g., triethylamine or diisopropylethylamine). In other embodiments, the base is an amidine or a non-nucleophilic base (e.g., 1,8-diazabicycloundec-7-ene (DBU) or 1,5-diazabicyclo[4.3.0]non-5-ene (DBN)).

[0034] In some embodiments of the invention, the base and / or aldehyde act as the solvent, while in other embodiments of the invention the solvent is a separate species, such as water, methanol, ethanol, isopropanol, 1,4-dioxane, N,N-dimethylformamide, etc.

[0035] In some embodiments of the present invention, the first electrode 311 and the second electrode 321 may include a defined flow channel for directing a fluid.

[0036] In some embodiments of the present invention, first electrode 311 and second electrode 321 are conductive carbon electrodes. In other embodiments of the present invention, first electrode 311 is a conductive carbon electrode and second electrode 321 comprises nickel, cobalt, iron, stainless steel, or platinum.

[0037] In some embodiments of the present invention, the ion selective membrane 330 is a cation conducting membrane such as Nafion® 212, FuMATech® E-630, or Selemion CMV-N®.

[0038] In some embodiments of the invention, second fluid stream 322 comprises hydrogen gas. In further embodiments of the invention, second electrode 321 is configured to allow hydrogen to be oxidized, thereby acting as an electron source, such as a gas diffusion electrode. In still further embodiments of the invention, second electrode 321 also contains an electrocatalyst for hydrogen oxidation, such as platinum.

[0039] In some embodiments of the present invention, second fluid stream 322 comprises methanol. In further embodiments of the present invention, second electrode 321 also contains an electrocatalyst for methanol oxidation, such as platinum-ruthenium.

[0040] In some embodiments of the present invention, the second fluid stream 322 comprises an aqueous solution of a salt of ferrocyanide (eg, sodium ferrocyanide, potassium ferrocyanide, or ammonium ferrocyanide).

[0041] In some embodiments of the invention, second fluid stream 322 comprises an aqueous solution of an alkali metal hydroxide (e.g., sodium hydroxide or potassium hydroxide). In further embodiments of the invention, second electrode 321 comprises a typical alkaline electrolytic cell material (e.g., nickel or stainless steel). In further embodiments of the invention, oxygen produced at second electrode 321 is used as an oxidant in process 1 to reoxidize first fluid stream 311.

[0042] In some embodiments of the invention, the aldehyde is not included in the first fluid stream 312, but is added to the first fluid stream 312 only after the current density in the split electrolyzer 300 falls below the threshold defined above, or after the applied potential exceeds a threshold, or after a predetermined amount of charge has passed. In further embodiments of the invention, the potential 340 between the first electrode 311 and the second electrode 321 is switched to an open circuit potential (a) after the current density in the split electrolyzer 300 falls below a threshold, (b) after the applied potential exceeds a threshold, or (c) after a predetermined amount of charge has passed, before the aldehyde is added to the first fluid stream 312.

[0043] In some aspects of the invention, the split electrolyzer 300 can be used as a redox flow battery cell without the need to replace the first electrode 311 or the second electrode 321 or the ion-conducting membrane 330. In further embodiments of the invention, the (α-hydroxy)alkylated product or dehydroxylated alkylated product produced in the first fluid stream 312 using the split electrolyzer 300 is not discharged from the first chamber 310 of the split electrolyzer 300, but is retained in the solution phase and used directly as the negative electrolyte (i.e., negolyte or anolyte) in a redox flow battery (the split electrolyzer 300 is a redox flow battery cell). In yet a further embodiment of the present invention, the second fluid stream 322 is not discharged from the second chamber 320 of the split electrolyzer 300 but is retained in solution phase and used directly as the positive electrolyte (i.e., posolyte or catholyte) of a redox flow battery (the split electrolyzer 300 is a redox flow battery cell). In a further embodiment of the present invention, both the first fluid stream 312 and the second fluid stream 322 are not discharged from the first chamber 310 and the second chamber 320 of the split electrolyzer 300, respectively, but are retained in solution phase and used directly as the negative and positive electrolytes of a redox flow battery (the split electrolyzer 300 is a redox flow battery cell), respectively, or used directly as the positive and negative electrolytes of a redox flow battery cell, respectively.

[0044] In further embodiments of the present invention, the charge states of the negative and positive electrolytes (formerly first fluid stream 312 and second fluid stream 322, or in some other embodiments, second fluid stream 312 and first fluid stream 322) may be individually adjusted or readjusted to maximize the capacity of the resulting redox flow battery. For example, first fluid stream 312 or second fluid stream 322 may be treated with an oxidizing agent (e.g., atmospheric oxygen, hydrogen peroxide, ozone, sodium hypochlorite, etc.), or first fluid stream 312 or second fluid stream 322 may be treated with a reducing agent (hydrogen, hydrazine, hydrazine hydrate, sodium thiosulfate, sodium dithionate, sodium sulfite, etc., with an optional catalyst).

[0045] In some embodiments of the present invention, the substituted anthraquinones and aldehydes in first fluid stream 312 are replaced by intermediates of the same type of reaction described above (i.e., different substituted anthraquinones containing a hydroxy or amine group at the 1-position and further containing a —CH(OH)—R group at the 2-position). In this case, the desired product will be dehydroxylated at the benzylic position of the 2-position substituent.

[0046] Action 1 After a predetermined time, or after a predetermined amount of charge has passed, the first fluid stream 312 is discharged from the first chamber 310 of the split electrolyzer 300, and an oxidant is introduced into the first fluid stream 312. In some embodiments of the present invention, the oxidant is in the gas phase and may be air, oxygen, ozone, or a mixture thereof. Alternatively, the oxidant may be a liquid or in a solution phase (including, but not limited to, dimethyl sulfoxide or hydrogen peroxide). The oxidant may be a solid, such as silver(I) oxide. Combinations of different oxidants may also be used. After a further predetermined time, the reaction product is isolated from the oxidized first fluid stream and, optionally, purified by conventional means well known to those skilled in the art.

[0047] Action 2 After a predetermined time or amount of charge has passed, second fluid stream 322 is optionally replaced by third fluid stream 325, and the potential 340 between first electrode 311 and second electrode 321 is reversed in sign, such that electrochemical oxidation of first fluid stream 312 replaces electrochemical reduction, and electrochemical reduction of second fluid stream 322 or third fluid stream 325 replaces electrochemical oxidation. After another predetermined time, or passage of a predetermined amount of charge, or a current density below a threshold, or an applied potential above a threshold, the oxidized first fluid stream 312 is discharged from first chamber 310 of split electrolyzer 300, and the reaction products are isolated and optionally purified by conventional means well known to those skilled in the art.

[0048] Action 3 After a predetermined time or amount of charge has passed, the first fluid stream 312 is discharged from the first chamber 310 of the split electrolytic cell 300. The discharged first fluid stream 362 flows through the third chamber 360 past the third electrode 361 of the second split electrolytic cell 350. The second split electrolytic cell 350 has a third fluid stream 372 flowing through its fourth electrode 371 through the fourth chamber 370. An electric potential 390 is applied to the third electrode 361 and the fourth electrode 371 of the second split electrolytic cell 350 such that the third electrode 361 is at a more positive potential relative to the fourth electrode 371. (i.e., the third electrode 361 is the anode and the fourth electrode 371 is the cathode 371.) After a further predetermined time, or passage of a predetermined amount of charge, or a current density below a threshold, or an applied potential above a threshold, the discharged first fluid stream 362, now oxidized, is discharged from the third chamber 360 of the second divided electrolytic cell 350, and the reaction products are isolated and optionally purified by conventional means well known to those skilled in the art (reprecipitation, recrystallization, filtration, distillation, washing, extraction, chromatography, etc.). [Example]

[0049] Example 1 In a Parr hydrogenator equipped with a mechanical stirrer, 3.00 g of 1,8-dihydroxyanthraquinone (12.49 mmol), 3.45 g of glyoxylic acid monohydrate (37.47 mmol, 3 equivalents), and 0.30 g of 5 wt% palladium on carbon were thoroughly mixed in 100 mL of 1.63 M NaOH solution. The reaction mixture was sparged with hydrogen gas for 3 minutes and then pressurized with hydrogen to reach a pressure of 100 psi. The reaction was stirred at room temperature (approximately 20 °C) for 1 hour and then heated to 80 °C for 1 hour. The vessel was vented, and the reaction mixture was poured onto ample ice to rapidly reduce the temperature to approximately room temperature. A stream of air was then bubbled through the reaction mixture for 30 minutes. The solution was acidified to pH 8-9 with 6 M hydrochloric acid and then filtered to remove the palladium on carbon catalyst and unreacted 1,8-dihydroxyanthraquinone. The filtrate was then further treated with concentrated hydrochloric acid to a pH of about 0, causing an ochre solid to precipitate from solution. The solid was collected by filtration and washed with cold water to give the crude product, 1,8-dihydroxy-2,7-bis(carboxymethyl)-9,10-anthraquinone (60% yield). The solid can be purified by recrystallization from hot water and, if necessary, dried.

[0050] Example 2 200cm 2An electrochemical cell ("MP Cell®", ElectroCell North America, Inc.) with an electrode area of ​​1000 kJ / cm² was constructed with a graphite felt cathode, a stainless steel anode, a Nafion® 115 membrane, a polypropylene flow frame, an EPDM gasket, a cathode reservoir for holding catholyte, and an anode reservoir for holding anolyte. The cathode reservoir had a capacity of approximately 2 liters and was maintained under an inert nitrogen atmosphere to prevent reoxidation of the reaction mixture by atmospheric oxygen, while the anode reservoir had a capacity of approximately 10 liters and was open to the atmosphere. Both reservoirs were equipped with heating elements to heat the anolyte and catholyte as needed. The anode reservoir was first filled with 2 liters of 3 M NaOH. Outside the cathode reservoir, catholyte was first prepared by mixing 137 mL of 50% NaOH solution, 33.8 g of glyoxylic acid monohydrate, and 30.0000 g (124.89 mmol) of 1,8-dihydroxyanthraquinone in enough deionized water to bring the total volume of catholyte to approximately 2.0 L. The cathode slurry was added to the cathode reservoir, and the pump was started to circulate both the catholyte and anolyte through the electrochemical cell. An additional 750 mL of deionized water was added to the catholyte, bringing the final catholyte volume to 2.75 L. The catholyte and anolyte were warmed to 40 °C and the temperature was slowly increased to 50 °C while a current of 40 mA / cm was applied. 2A constant current of 4 A (total current) was passed. During operation, oxygen gas was evolved at the anode while the catholyte solution was reduced. After two equivalents of charge relative to 1,8-dihydroxyanthraquinone had passed (249.78 mmol, 24,100 coulombs), the temperature was raised to 65 °C and held there until a total of 4.1 equivalents of charge (512.05 mmol, 49,405 coulombs) had passed. HPLC analysis of the aerated aliquot showed that no 1,8-dihydroxyanthraquinone remained in solution and that the target molecule, 2,7-bis(carboxymethyl)-1,8-dihydroxyanthraquinone (DCDHAQ), was present at approximately 86% purity. Some impurities observed by HPLC (British Pharmacopeia 2004 for Dantron: C18 column, eluted isocratically with a mixture of 2.5 volumes of glacial acetic acid, 40 volumes of tetrahydrofuran, and 60 volumes of water, flow rate 1 mL / min, run time 40 min, detection at 254 nm) included the intermediate compounds 2,7-bis(α-hydroxy-carboxymethyl)-1,8-dihydroxyanthraquinone and 2-(α-hydroxy-carboxymethyl)-7-carboxymethyl-1,8-dihydroxyanthraquinone, which can be converted to the target molecule DCDHAQ by reduction in an electrochemical cell or through the process of cycling in a flow battery cell. Other impurities include 2,2'-(1,8-dihydroxy-9-oxo-9,10-dihydroanthracene-2,7-diyl)diacetic acid, 2,2'-(1,8-dihydroxy-10-oxo-9,10-dihydroanthracene-2,7-diyl)diacetic acid, 2,2',2'',2'''-(4,4',5,5'-tetrahydroxy-10,10'-dioxo-9,9',10,10'-tetrahydro-[9,9'-bianthracene]-3,3',6,6'-tetrayl)tetraacetic acid, and related isomers. In general, anthrone and dianthrone can then be converted to the target molecule DCDHAQ through oxidation in an electrochemical cell, prolonged exposure to atmospheric oxygen, or cycling in a flow battery (Reference ChemRxiv 2021, DOI: 10.26434 / chemrxiv-2021-x05x1).Therefore, the catholyte solution from this synthesis can be used directly as the negolyte reactant in a flow battery without downstream processing, optionally with some concentration by solvent evaporation to save costs and reduce chemical waste. To isolate the product, DCDHAQ, the catholyte solution was drained through a filter, exposed to air to completely re-oxidize the solution, and re-filtered. The filtrate was acidified with 15% hydrochloric acid to a pH <1, and the precipitated solid was filtered and dried overnight at 45°C. The dried solid turned from orange to deep red upon grinding. Isolated yield: 30.1393 g (67.7%), melting point 260-262°C. The majority of the loss was likely due to hard masses of unreacted, undissolved 1,8-dihydroxyanthraquinone, which remained unreacted and was later removed by filtration. The solid can be repurified, if necessary, to a purity of >98% DCDHAQ (HPLC) by dissolving 1 g of the solid in 4 mL of dimethyl sulfoxide and adding 12 mL of deionized water to form a precipitate, followed by filtration, washing with deionized water, and drying. The NMR spectrum of the DCDHAQ produced in this example was identical to that reported in the literature (see J. Mater. Chem. A, 2021, 9, 26709-26716). 1 H NMR(500MHz,DMSO-d6)δ 12.43(s,2H),12.24(s,2H),7.76(dd,J=7.5Hz,2H),7.68(dd,J=7.5Hz,2H),3.71(s,4H).

[0051] Example 3 A solution of 2,7-bis(α-hydroxy-carboxymethyl)-1,8-dihydroxyanthraquinone was prepared by first stirring 2.60 liters of deionized water, 78 mL of 50% NaOH, 128 mL of 45% KOH, 80.9 g of 1,8-dihydroxyanthraquinone, and 70.6 g of sodium dithionite under argon for 5 minutes at room temperature, followed by the addition of a solution of 91.7 g of glyoxylic acid monohydrate in 200 mL of a solution containing 0.5 M NaOH and 0.5 M KOH, which was added dropwise over 256 minutes using an addition funnel. Upon completion of the addition, the reaction mixture was exposed to air and filtered to produce a solution of 2,7-bis(α-hydroxy-carboxymethyl)-1,8-dihydroxyanthraquinone, along with excess NaOH / KOH and other reactants. Separately, as in Example 2, 200 cm 2 An electrochemical cell ("MP Cell®", ElectroCell North America, Inc.) with an electrode area of ​​1000 nm was constructed with a graphite felt cathode, a stainless steel anode, a Nafion® 115 membrane, a polypropylene flow frame, an EPDM gasket, a cathode reservoir for holding catholyte, and an anode reservoir for holding anolyte. The cathode reservoir had a volume of approximately 2 liters and was maintained under an inert nitrogen atmosphere to prevent reoxidation of the reaction mixture by atmospheric oxygen, while the anode reservoir had a volume of approximately 10 liters and was open to the atmosphere. Both reservoirs were equipped with heating elements to heat the anolyte and catholyte as needed. A solution of 2,7-bis(α-hydroxy-carboxymethyl)-1,8-dihydroxyanthraquinone was then preheated to 65°C and poured into the cathode reservoir, which was maintained under nitrogen. Separately, 4 liters of 3 M NaOH solution was preheated to 65 °C and poured into the anode reservoir, which was left open to air. The catholyte and anolyte solutions were circulated through the cathode and anode chambers of the electrochemical cell using pumps, respectively, at 50 mA / cm while maintaining the solution temperature within the range of 51–71 °C. 2Current was passed at a constant current density of 10 A (total current). The current was stopped when 4 molar equivalents of charge (34.98 Ah) had passed. For most experiments, near the end of the experiment, the cell voltage rose sharply from an original value of 1.5–1.6 V to 2.3–2.4 V. The catholyte was drained from the cathode reservoir, reoxidized by exposure to atmospheric oxygen, and filtered to remove any solids. The filtrate was acidified with 15% HCl to a pH of approximately 1, and the precipitate was filtered, washed with water, and dried. The crude material was redissolved in aqueous KOH, reacidified, recollected by filtration, and washed again with water to obtain the target molecule, 2,7-bis(carboxymethyl)-1,8-dihydroxyanthraquinone. Yield: 80.0 g (66.7%) for 1,8-dihydroxyanthraquinone. Most of the loss was due to incomplete dissolution of 1,8-dihydroxyanthraquinone, which was removed unreacted in the first filtration.

[0052] Unless otherwise indicated, all numbers expressing size, amount, volume, area, concentration, frequency, temperature, and other chemical and physical properties of features used in the specification and claims are to be understood as modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and appended claims are approximations and may vary depending upon the desired properties sought to be obtained by those of ordinary skill in the art utilizing the teachings disclosed herein. The use of numerical ranges by endpoints includes all numbers within that range (e.g., 1-5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5; <10% includes 10%, 9.8%, 5.5%, 2%, 0.01%, and 0%; >90% includes 90%, 90.2%, 94.5%, 98%, 99.99%, and 100%) and any range within that range.

[0053] The foregoing description has been presented for purposes of illustration and description. The disclosure is not intended to be exhaustive or to limit the embodiments to the precise form disclosed. Many modifications and variations are possible in light of the above teachings. Any or all features of the embodiments of the present disclosure may be applied individually or in any combination and are intended to be purely illustrative, not limiting. It is intended that the scope of the invention be determined not by this detailed description, but rather by the appended claims. [Explanation of symbols]

[0054] 300...Divided electrolytic cell 310 First chamber 311... First electrode 312... First fluid flow 313 First chamber entrance 314 First chamber outlet 320 Second Chamber 321... Second electrode 322...Second Fluid Stream 323 Second chamber entrance 323 Second chamber entrance 325...Third Fluid Stream 330 Ion-conducting membrane 340...potential 350...Second divided electrolytic cell 360...Third Chamber 361...Third electrode 362...First fluid flow 370 Fourth Chamber 371...Fourth electrode 372···Third Fluid Flow 390...potential

Claims

1. An apparatus for (α-hydroxy) alkylating or alkylating an anthraquinone derivative selected from the group consisting of Formula I, Formula II, Formula III, and Formula IV by reacting the 2-position with an aldehyde, comprising: 【Chemistry 1】 (wherein X is a hydroxyl group or an amino group, and X １ and X ２ are each independently a hydroxyl group or an amino group, and the 2-position of the anthraquinone derivative is １ , and X ２ (The ortho positions of each of the groups are unsubstituted.) A split electrolytic cell, a first chamber having a first electrode configured to receive a first fluid stream comprising an anthraquinone derivative of Formula I, Formula II, Formula III, or Formula IV, an aldehyde, a base, and an optional solvent, and to electrochemically react with the first fluid stream; a second chamber having a second electrode configured to receive the second fluid stream and to electrochemically react with the second fluid stream; Including, A split electrolytic cell in which a first chamber and a first electrode are separated from a second chamber and a second electrode by an ion-conducting membrane.

1. An apparatus comprising:

2. 10. The apparatus of claim 1, wherein the first fluid stream is configured to be recirculated to the first chamber and the second fluid stream is configured to be recirculated to the second chamber.

3. The apparatus of claim 1 , wherein at least one of the first electrode and the second electrode comprises an electrocatalyst or an electrocatalyst precursor.

4. The apparatus of claim 1 , further comprising an electrical power supply configured to apply an electrical potential between the first electrode and the second electrode.

5. 10. The apparatus of claim 1, wherein the base in the first fluid stream comprises a base selected from the group consisting of inorganic hydroxides, metal alkoxides, amines, amidines, or mixtures thereof.

6. 6. The apparatus of claim 5, wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, or a mixture thereof.

7. The device of claim 1 , wherein the solvent is water.

8. The device of claim 1 , wherein the ion-conducting membrane is a cation-exchange membrane.

9. the ion-conducting membrane is a cation-exchange membrane, the second fluid stream comprises an aqueous solution comprising sodium hydroxide, potassium hydroxide, or a mixture thereof; the second electrode is made of nickel, cobalt, iron, stainless steel, platinum, or a mixture thereof; The device of claim 6 , wherein the device further comprises a solvent comprising water.

10. 10. The apparatus of claim 9, wherein oxygen produced at the second electrode is used to oxidize the first fluid stream after the electrochemical reduction is completed.

11. the ion-conducting membrane is a cation-exchange membrane, the second fluid stream comprises hydrogen gas; a second electrode configured to allow hydrogen to be oxidized, thereby acting as a source of electrons; The device of claim 6 , wherein the device further comprises a solvent comprising water.

12. The apparatus of claim 11 , wherein the second electrode further comprises an electrocatalyst comprising platinum.

13. the ion-conducting membrane is a cation-exchange membrane, the second fluid stream comprises methanol; The device of claim 6 , wherein the device further comprises a solvent comprising water.

14. The device of claim 12 , wherein the second electrode further comprises an electrocatalyst comprising platinum-ruthenium.

15. A redox flow battery configured to utilize a first flow battery reactant and a second flow battery reactant to store and release electrical energy, wherein the redox flow battery can further react with an aldehyde to (α-hydroxy)alkylate or alkylate the 2-position of an anthraquinone derivative selected from the group consisting of Formula I, Formula II, Formula III, and Formula IV; 【Chemistry 2】 (wherein X is a hydroxyl group or an amino group, and X １ and X ２ are each independently a hydroxyl group or an amino group, and the 2-position of the anthraquinone derivative is １ , and X ２ and are unsubstituted.) A split electrolytic cell, a first chamber having a first electrode configured to receive a first fluid stream comprising an anthraquinone derivative of Formula I, Formula II, Formula III, or Formula IV, an aldehyde, a base, and an optional solvent, and to electrochemically react with the first fluid stream; a second chamber having a second electrode configured to receive the second fluid stream and to electrochemically react with the second fluid stream; Including, A split electrolytic cell in which a first chamber and a first electrode are separated from a second chamber and a second electrode by an ion-conducting membrane. Including, The redox flow battery utilizes the anthraquinone derivative that is (α-hydroxy)alkylated or alkylated at the 2-position and remains in a first fluid stream as a first flow battery reactant, and utilizes a second fluid stream as a second flow battery reactant.

16. the ion-conducting membrane is a cation-exchange membrane, the first and second fluid streams comprise an aqueous solution selected from the group consisting of sodium hydroxide, potassium hydroxide, or a mixture thereof; the first and second electrodes are selected from the group consisting of graphite, carbon black, carbon felt, carbon cloth, carbon paper, carbon nanotubes, other forms of conductive carbon, or mixtures thereof; 16. The redox flow battery of claim 15, wherein the redox flow battery further comprises a solvent comprising water.

17. 17. The redox flow battery of claim 16, wherein the second fluid stream further comprises sodium ferrocyanide, sodium ferricyanide, potassium ferrocyanide, potassium ferricyanide, or a combination thereof.

18. A method for (α-hydroxy) alkylating or alkylating an anthraquinone derivative selected from the group consisting of Formula I, Formula II, Formula III, and Formula IV by reacting the 2-position with an aldehyde, comprising the steps of: 【Transformation 3】 (wherein X is a hydroxyl group or an amino group, and X １ and X ２ are each independently a hydroxyl group or an amino group, and the 2-position of the anthraquinone derivative is １ , and X ２ and are unsubstituted.) A split electrolytic cell is provided, the split electrolytic cell comprising: a first chamber having a first electrode configured to receive a first fluid stream comprising an anthraquinone derivative of Formula I, Formula II, Formula III, or Formula IV, an aldehyde, a base, and an optional solvent, and to electrochemically react with the first fluid stream; a second chamber having a second electrode configured to receive the second fluid stream and to electrochemically react with the second fluid stream; Including, providing a split electrolytic cell, wherein a first chamber and a first electrode are separated from a second chamber and a second electrode by an ion-conducting membrane; flowing a first fluid stream through a first chamber and contacting a first electrode; flowing a second fluid stream through the second chamber and contacting a second electrode; applying an electrical potential between the first electrode and the second electrode to induce an electrochemical reduction reaction in the first fluid stream and an electrochemical oxidation reaction in the second fluid stream; A method comprising:

19. 20. The method of claim 18, wherein the first fluid stream is configured to recirculate through a first chamber having a first electrode.

20. waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; Discharging the first fluid stream from the first chamber; introducing an oxidant into the reaction mixture obtained from the discharged first fluid stream; isolating the product from the reaction mixture; and 20. The method of claim 18, further comprising:

21. waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; reversing the sign of the potential between the first electrode and the second electrode such that an electrochemical oxidation reaction occurs in the first fluid stream and an electrochemical reduction reaction occurs in the second fluid stream; waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; Discharging the first fluid stream from the first chamber; isolating a product from the discharged first fluid stream; 20. The method of claim 18, further comprising:

22. waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; replacing the second fluid stream with a third fluid stream; reversing the sign of the potential between the first electrode and the second electrode such that an electrochemical oxidation reaction occurs in the first fluid stream and an electrochemical reduction reaction occurs in the third fluid stream; waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; Discharging the first fluid stream from the first chamber; isolating a product from the discharged first fluid stream; 20. The method of claim 18, further comprising:

23. waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; Discharging the first fluid stream from the first chamber to obtain an intermediate fluid stream; providing a second split electrolytic cell, the second split electrolytic cell comprising: a third chamber having a third electrode configured to receive the intermediate fluid stream and to electrochemically react with the intermediate fluid stream; a fourth chamber having a fourth electrode configured to receive the third fluid stream and to electrochemically react with the third fluid stream; Further comprising: providing a split electrolytic cell, wherein a third chamber and a third electrode are separated from a fourth chamber and a fourth electrode by a second ion-conducting membrane; passing the intermediate fluid stream through a third chamber and contacting a third electrode of a second segmented electrolytic cell; passing a third fluid stream through the fourth chamber and contacting a fourth electrode of the second divided electrolytic cell; applying an electrical potential between a third electrode and a fourth electrode to induce an electrochemical oxidation reaction in the intermediate fluid stream and an electrochemical reduction reaction in the third fluid stream; 20. The method of claim 18, further comprising:

24. 24. The method of claim 23, wherein the intermediate fluid stream is configured to recirculate to a third chamber having a third electrode.

25. waiting until a threshold time has elapsed or a threshold amount of charge has passed, or until the current density falls below a threshold, or after the applied potential exceeds a threshold; discharging the intermediate fluid stream from a third chamber to obtain a product fluid stream; isolating a product from said product fluid stream; 24. The method of claim 23, further comprising:

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