Patent Application
20250066294
This invention relates to a method for preparing ionic compounds which may find application in various fields such as electrochemistry, catalysis, materials chemistry, among which it is worth mentioning the field of rechargeable batteries, especially lithium and sodium batteries. This invention also relates to a synthetic intermediate in the route leading to said ionic compounds.
Electrolytes enable, according to their ionic conductivity, the movement of ions from the cathode to the anode on charge and in reverse on discharge. The electrolyte of a battery may consist of soluble salts, acids or other bases in liquid, gelled and dry formats. For example, it is well known that the salts of strong acids such as HClO4, HBF4, HPF6 and HRFSO3 (RF=perfluoroalkyl radical) have electrochemical properties. The “superacids” obtained by adding a Lewis acid such as SbF5 to the abovementioned compounds are also known. However, these compounds are not stable other than in protonated form and in non-solvating media such as aliphatic hydrocarbons. The salts are unstable in the usual polar solvents.
Electrolytes can also be polymeric. The conductivity of polymer electrolytes, which is intrinsically low as they are primarily organic and contain ions only adventitiously in very small concentrations, may be increased by the addition of certain amounts of ionic compounds (or salts).
In particular, ionic compounds such as perfluoroalkylsulfonimide derivatives M[RFSO2NSO2RF] (RF=perfluoroalkyl) have recently raised more attention across various chemical fields. They have advantageous stability properties in protonated form (M is H) or in the form of salts (M is commonly a metal) and are used as solutes in electrochemistry and as catalysts. However, it is challenging to give these salts all desirable properties required for their applications, in particular in terms of properties such as acidity, dissociation ability or solubility. Among known M[RFSO2NSO2RF] derivatives, lithium bis(trifluoromethansulfonyl)imide (Li[(CF3SO2)2N], also abbreviated as LiTFSI, has been studied in recent years as a potential replacement of lithium hexafluorophosphate (LiPF6), which currently dominates the landscape of ionic compounds for non-aqueous liquid electrolytes. LiTFSI is more chemically and thermally stable when compared to LiPF6 and has already found application as conducting salt in aqueous electrolytes of lithium batteries having lithium metal as anode.
H. Zhang et al. (J. Power Sources 2015, 296, 142-149) report the physiochemical and electrochemical characterization of neat LisTFSI, namely [CF3—S(O)2—N−—S(O)(CF3)—N—S(O)2−CF3], and its carbonated-based liquid electrolytes compared to LiPF6, LiTFSI and (Li[(C2F5SO2)2N] (abbreviated as LiBETI). The liquid electrolyte is formed from LisTFSI in a mixture of ethylene carbonate (EC) and ethyl-methyl-carbonate (EMC) with small amounts of water. Despite the higher dissociation ability of LisTFSI, compared to the parent compound LiTFSI, its ionic conductivity was found to be smaller than that of LiTFSI, which is attributed to the larger anionic volume of [sTFSI]−compared to that of [TFSI]−.
H. Zhang et al. (ChemElectroChem 2021, 8, 1322-1328) disclose a LisTFSI/PEO (poly(ethylene oxide)) membrane that is characterized by a slightly superior Li+ ion only conductivity but again considerably lower total ionic conductivity compared to those of a standard LiTFSI/PEO solid electrolyte.
Based on the higher dissociation ability of LisTFSI, a higher Li+ mobility was expected, however these data reinforce the idea that the structural optimization of a conductive salt, especially in terms of its total conductivity, is not a trivial task.
At the same time, it is concerning that the routes to new and potentially useful perfluorosulfonimide derivatives are based on time-consuming, wasteful and scope-limited synthetic steps. The first synthesis of K[sTFSI] (the corresponding potassium salt of the compound disclosed in H. Zhang et al., ChemElectroChem 2021, 8, 1322-1328) was reported more than a decade ago by R. Y. Garlyauskayte et al. (Org. Biomol. Chem. 2005, 3, 2239-2243) and it is still adopted nowadays to access ionic compounds of formula M[sTFSI] salts (M is a cation), which offer a fertile ground for optimization of electrolytes in secondary cell and battery applications. R. Y. Garlyauskayte et al. describe two sulfoximidoyl fluoride intermediates, PhS(O)(NSO2CF3)F (1) and CF3S(O)(NSO2CF3)F (2), which act as synthons for the synthesis of salts of perfluorosulfonimide derivatives. However, PhS(O)(NSO2CF3)F (1) only afforded symmetric perfluorosulfonimide dimers by reaction with Li3N in the presence of dimethylaminopyridine as catalyst and subsequent treatment with KCl. The inherent limitation of this method through intermediate (1) is that unsymmetric perfluorosulfonimides cannot be obtained. Using the same method, intermediate (2) gave very low product yields and the isolation was unsuccessful. On the other hand, by changing the reaction conditions, the intermediate CF3S(O)(NSO2CF3)F (2) was converted to two perfluorosulfonimide salts via a one-pot two-steps sequence involving a) reaction with amides in presence of pyridine in a methylene chloride solution and b) exchange of the pyridinium cation with a potassium cation by either use of an ion-exchange resin (such as Dowex 50WX8-200, K+ form) or reaction with K2CO3 in methylene chloride. Even though the products are symmetric, in principle the same route could afford unsymmetric salts. Despite its higher modulability, it is apparent that the synthetic efficiency of the second method is affected by the electronic nature of the starting materials as intermediate (1) only led to a 25% isolated product yield. Additionally, the full route to perfluorosulfonimide salts via the intermediate CF3S(O)(NSO2CF3)F (2) (shown below) displays a number of drawbacks such as a long sequence (5 steps starting from the precursor CF3SO2NH2), long overall reaction time (ca. 12 hours), use of environmentally-unfriendly reagents (CF3SiMe3 is prepared from bromotrifluoromethane, a well-known depleter of the stratospheric ozone layer), poor atom-economy (excess of CsF generates fluorine waste), cryogenic conditions, narrow nucleophile scope (the anionic S(IV) intermediate only reacts with F31 ) and the complex purification of intermediates (1) and (2) which are moisture sensitive.
U.S. Pat. No. 6,340,716B1 describes a wide range of ionic compounds that are useful for the production of ion conducting materials or electrolytes, as catalysts and for doping polymers, though the general synthetic procedures do not depart from what is taught by R. Y. Garlyauskayte et al.
This document reports that a compound of formula [R1SO2N—S*(═O)(R2)═NSO2R3][M] (such as, i.e. LisTFSI) can be obtained by reacting a salt [R1SO2N—S*(═O)(R2)][M] with a halogenating agent, to give the intermediate [R1SO2N—S*(═O)(R2)(X)] (X being a halogen), which is structurally analogous to intermediate (2) described earlier. Said precursor is then condensed with a sulfonamide R3SO2NH2 in the presence of a base or with the metallic derivatives of the sulfonamide, such as R3SO2NLi2 or R3SO2NNa2. The desired cation for the final compound is obtained by standard ion-exchange processes.
In view of the drawbacks associated to a route involving an intermediate of formula [R1SO2N—S*(═O)(R2)(X)] as detailed above, more sustainable procedures to prepare sulfonimide salts should be sought after, in particular with the aim of finding new ionic compounds for use in solid electrolytes that possess high ionic conductivity.
Thus, the aim of the present invention is the provision of a less wasteful, step-economical and facile method to prepare ionic compounds with a sulfonimide backbone which not only display a high delocalization of the anionic charge and improved dissociation ability, but can be also comprised in solid-state electrolyte to improve the total ionic conductivity.
The inventors have devised a new method to prepare ionic compounds (more conveniently called “salts”, from hereinafter) of formula I as defined elsewhere herein, said compounds feature high delocalization of the negative charge in the anion and can patently increase the total ionic conductivity of a solid electrolyte in which they can be comprised. The anion of salt I involves an S—N—S—N—S core where sulfur atoms are hexavalent and the negative charge is delocalized between the two nitrogen atoms and the five oxygen atoms linked to the sulfur atoms; and, specifically, a group (E) and two groups R1 and R2 are directly attached to the S—N—S—N—S core. It has unexpectedly been found that salts of this type lead to improved solid electrolytes that are more conductive than reported solid electrolyte comprising analogous salts with no fluorine substituents linked to any of the sulfur atoms.
The method described herein is performed in one-pot and displays several advantages compared to prior art, among these: higher step-and atom-economy, milder conditions, as well as the ability to synthesize a broad range of salts having high negative charge delocalization as mentioned above.
Therefore, in a first aspect, the present invention refers to a method to obtain a salt of formula I:
wherein:
The method can be illustrated according to the general scheme below:
The process can also include an optional step wherein a fluoride radical at E position in the general formula (I) is replaced by a different radical E, namely by a C1-C16 alkyl radical or an amine radical N(R4)(R5) by nucleophilic substitution reactions.
Furthermore, an additional cation exchange step may be performed where the cation M is replaced by a different cation M′. In the particular case wherein it is desired to obtain a salt of formula (I) wherein the cation is a mono-or di-valent cation different from that in compounds III and IV or is a trivalent, such as Al3+, or a polyonium cation, the salt of formula (I) resulting from step b) is subjected to said cation exchange step. A skilled person would know how to perform such additional step, generally by reacting the salt containing the cation M with a suitable salt containing the other cation M′ or directly with a M′ in a solvent, adjusting the amounts of the reacting salts so that the charges of the anion and the cation are balanced, and letting the exchange reaction go to completion.
In another aspect, the invention refers to a dianionic compound of formula (IV):
wherein
The present invention refers to a method to obtain a salt of formula I:
wherein:
wherein R1 is as defined above;
The subscripts “m” and “n” are integer positive numbers equal to 1, 2 or 3 and refer to the number of cations or anions needed to neutralize the charge of the corresponding counterion, respectively, so that the ionic compound is overall neutral. Preferably, m is 1 or 2. Also preferably n is 1 or 2.
The term “alkyl radical” refers to an alkane-derived radical which is bound to the rest of the molecule through a single bond. It may be linear or branched. It preferably comprises from 1 to 16 (“C1-C16 alkyl”), preferably from 1 to 8 (“C1-C8 alkyl”), even more preferably from 1 to 4 (“C1-C4 alkyl”) carbon atoms. Illustrative examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, pentyl, hexyl, heptyl, octyl.
The term “aryl radical” refers to an aromatic group, preferably having between 6 and 10 carbon atoms (“C6-C10 aryl”), which may comprise 1 aromatic ring or 2 aromatic rings fused to one another. Illustrative examples of aryl groups include phenyl, naphthyl or indenyl. Preferably, it is phenyl.
The term “alkenyl radical” refers to an alkene-derived radical which is bound to the rest of the molecule through a single bond. It may be linear or branched. It preferably comprises from 2 to 16 (“C2-C16 alkenyl”), preferably from 2 to 8 (“C2-C8 alkenyl”), even more preferably from 2 to 4 (“C2-C4 alkenyl”) carbon atoms.
The term “alkynyl radical” refers to an alkyne derived radical which is bound to the rest of the molecule through a single bond. It may be linear or branched. It preferably comprises from 2 to 16 (“C2-C16 alkynyl”), preferably from 2 to 8 (“C2-C8 alkynyl”), even more preferably from 2 to 4 (“C2-C4 alkynyl”) carbon atoms.
The term “alkylaryl radical” refers to a radical derived from a group comprising an alkyl as defined above bearing at least an aryl group as described above along the alkyl chain and which is bound to the rest of the molecule through the alkyl group.
The term “arylalkyl radical” refers to a radical derived from a group comprising an alkyl as defined above bearing at least an aryl group as described above along the alkyl chain and which is bound to the rest of the molecule through the aryl group.
The term “alkylene oxide radical” refers to a radical derived from a saturated aliphatic chain containing alkylene oxide units which is bound to rest of the molecule through a single bond. It may be linear or branched. The alkylene portion refers to an alkane-derived diradical. The term “alkylene” is generally employed as meaning non-terminal alkyl moieties. The alkylene oxide radical can be depicted through general formula -(alkylene-O)xRao, wherein x is from 1 to 5, more preferably 1 or 2; the alkylene portion comprises from 1 to 16 (“C1-C16 alkylene”), preferably from 1 to 8 (“C1-C8 alkylene”), even more preferably from 1 to 4 (“C1-C4 alkylene”) carbon atoms; and Rao is H or alkyl as described above, preferably H or methyl, more preferably H. Preferably, the alkylene oxide units are ethylene or propylene oxide units, namely —(CH2CH20)xRao or —(CH2CH2CH2O)xRao, wherein x and Rao are as described above. Most preferably, the alkylene oxide units are such ethylene oxide units.
The term “alkylene imine” refers to a radical derived from a saturated aliphatic chain containing alkylene imine units which is bound to rest of the molecule through a single bond. It may be linear or branched. The alkylene portion refers to an alkane-derived diradical. The alkylene oxide radical can be depicted through general formula -(alkylene-NH)xRao, wherein x is from 1 to 5, more preferably 1 or 2; the alkylene portion comprises from 1 to 16 (“C1-C16 alkylene”), preferably from 1 to 8 (“C1-C8 alkylene”), even more preferably from 1 to 4 (“C1-C4 alkylene”) carbon atoms; and Rao is H or alkyl as described above, preferably H or methyl, more preferably H. Preferably, the alkylene imine units are ethylene or propylene imine units, namely —(CH2CH2NH)xRao or —(CH2CH2CH2 NH)xRao, wherein x and Rao are as described above. Most preferably, the alkylene imine units are such ethylene imine units. The N—H group may also be substituted by an N-alkyl group, wherein alkyl has the meaning described above.
The term “halogen” refers to bromine, chlorine, iodine or fluorine.
The term “polyonium” refers to a polycation comprising two or more organic onium cations as described below which are preferably connected intramolecularly by organic linkers, such as those comprising 1 to 8 carbons, such as C1-C8 alkylene, e.g. methylene, ethylene, propylene or butylene. The molecular structure of polyonium cations used in the present invention can be, without being limited thereto, a linear-chain structure, branched structure, and ring-shaped structure. Examples of polyonium include polyammonium, polyphosphonium, polypyridinium, polypyrrolidonium, polyimidazolium, polyimidazolinium and polysulfonium cations. In an embodiment, the polyonium comprises at least 10 onium cations, such as at least 100 or at least 1000 onium cations. In an embodiment, the polyonium comprises up to 3000 onium cations.
The terms fluorination reagent, chlorination reagent, bromination reagent and iodination reagent, refer to compounds that are capable to react with the compound of formula (IV) by releasing an electrophilic fluorine, a chlorine, a bromine or a iodine atom, respectively, thus forming a new S—F, S—Cl, S—Br or C—I bond while oxidazing the central S from oxidation state (IV) to oxidation state (VI). Examples of these reagents include 1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (also known as F-TEDA or selectfluor), N-fluorobenzenesulfonimides, such as N-Fluorobenzenesulfonimide (NFSI) and fluoropyridinium salts, such as N-fluoropyridinium triflatetetrafluoroborate; bromination reagents, such as N-Bromosuccinimide (NBS); chlorination reagents, such as N-Chlorosuccinimide (NCS); iodination reagents as N-Iodosuccinimide (NIS).
The term “alkylation reagent” refers to compounds that are capable to react with the compound of formula (IV) by releasing an electrophilic alkyl group (as defined above) optionally substituted with at least one F, an alkenyl, an aryl, —N(R6)(R7) or OR8 (as also defined elsewhere herein), thus forming a new S—C bond while oxidazing the central S from oxidation state (IV) to oxidation state (VI). Examples of alkylation reagents are iodoalkanes (e.g. iodomethane), alkyl triflates (e.g. methyl triflate), trimethyloxonium tetrafluoroborate, alkyl bromides (e.g. CH3Br, CH2CH3Br).
The term “fluoroalkylation reagent” refers to compounds that are capable to react with the compound of formula (IV) by releasing an electrophilic fluoroalkyl group, namely an alkyl group (as defined above) where at least one C—H group is substituted by a C—F groups, thus forming a new S—C bond. Preferably, a fluoroalkylation reagent is a perfluoroalkylation reagent able to release an electrophilic perfluoroalkyl group (RF), where all C—H groups are substituted by C—F groups, thus forming a new S—RF bond Typical examples of perfluoroalkylation reagents are Togni reagents (I and II), Langlois reagent (CF3SO2Na), Umemoto's reagent, which are either commercial or can be accessed by reported methods (for example, Chem. Commun., 2016, 52, 4049-4052).
The term “amination reagent” refers to compounds that are capable to react with the compound of formula (IV) by releasing an electrophilic N(R4)(R5) group (R4 and R5 are as defined above), thus forming a new S—N(R4)(R5) bond. Typical examples of suitable aminations reagents are chloroamines ClN(R4)(R5), which can be either commercially available or prepared by treating the corresponding secondary amines HN(R4)(R5) with aqueous hypochlorous acid. In an embodiment, when double substitution at an amine nitrogen with a given group, such as Y2, R′2, (R4)(R5) or (R6)(R7), is indicated, each of the two specific substituents chosen from that group is selected independently from the other. In another embodiment, said substituents are the same.
The inventors have found that a method for preparing the ionic compounds of formula I according to the procedure detailed in the description and examples of the present disclosure display several advantages.
In particular, the method of the invention can be carried in a one-pot manner. A “one-pot” reaction implies that a sequence of steps (in the present case, two steps) are performed consecutively in the same reaction vessel, meaning that further experimental operations such as solvent concentration or evaporation, extraction and/or other purification techniques are not required between a step and the subsequent one. This represents a considerable advantage in terms of reagents and time economy.
Another advantage of the present method is that the reaction conditions are milder than those in previous reports. For example, the method can be carried out at temperatures comprised between −20° C. and room temperature in contrast to temperatures of −50° C. that are required to obtain some of the ionic compounds described in previous reports (J. Chem. Soc., Perkin Trans. 1, 2002, 1887-1889).
Further, the method of the invention features high step-and reagent-economy as the longest linear sequence is carried out in 4 steps including the optional metal-cation exchange step while the traditional route (see background of the invention) is performed in a 5-steps linear sequence. Furthermore, TMSCF3 (prepared from BrCF3, which is environmentally harmful) is avoided. The excess of CsF (2 equivalents) is replaced by a nearly stoichiometric amount of reagents (such as F-TEDA in the example below). Finally, the intermediates RS(O)(NSO2CF3)F (R is CF3 or Ph) in previous reports are poorly stable towards moisture and require a complex purification procedure while the current method is performed in a one-pot manner as said above, therefore exposure to moisture and air is minimized and the reagents and final products are stable and easy to handle.
Finally, the modulability with regards to the groups R1, R2 and E allows to obtain a wide scope of ionic compounds.
As detailed herein below, the method of the present invention is performed in a one-pot two-step sequence and, optionally, additional steps may be performed.
In the context of the present invention, the terms “ionic compound” and “salt” will be used interchangeably. The ionic compounds synthesized according to the process of the invention comprise a cation M and an anion of formula:
wherein the subscript “n” is a positive integer number that refers to the number of anions needed to neutralize the charge of the cation M. The negative charge in the anion is represented for the sake of illustration on one nitrogen atom, however, it is a delocalized negative charge that is distributed due to resonance over the two nitrogen atoms and the five oxygen atoms in the anion of the general formula I. Even though one N—S bond (where S is the central sulphur atom) is graphically represented with a single bond while the other N—S bond (again, where S is the central sulphur atom) with a double bond, it has to be understood that both N—S bonds have an intermediate character between that of a single and double bond due to resonance.
The cation M in the compound of formula I can be a number of organic, organometallic and inorganic species that are able to carry one or more positive charges.
In a preferred embodiment, M is an alkali metal, that is, a metal of the group 1 of the periodic table that forms a monovalent cation M+. In a preferred embodiment, M is an alkali metal chosen from Lit, Na+, K+ and Cs+. More preferred alkali metals are Li+, Na+ and K+. Even more preferably, the alkali metal is Li+.
In another embodiment, M is an alkaline earth metal, that is, a metal of the group 2 of the periodic table that forms a divalent metal cation M2+. In a preferred embodiment, the alkaline earth metal is selected from Mg2+, Ca2+ and Ba2+.
In another embodiment, M is a transition metal with a valency comprised between 1 and 3. In a preferred embodiment, M is a transition metal selected from the group consisting of Cu2+, Zn2+, Fe2+ and Al3+.
In another embodiment, M is a rare-earth metal.
In another embodiment, M is a onium or polyonium cation.
In a preferred embodiment, the cation M is selected from the group of metal cations consisting of K+, Li+, Na+, Cs+, Mg2+, Ca2+, Ba2+, Cu2+, Zn2+, Fe2+, or Al3+.
In another embodiment, M in the compound of formula I is:
In a preferred embodiment, the method of the invention affords an ionic compound of formula I wherein M is Li+, Na+ or K+. More preferably, M is K+ and thus m=1.
In another embodiment, the cation M is an organic onium cation, namely a cation obtained by the protonation of a mononuclear hydride of a pnictogen (group 15 of the periodic table), chalcogen (group 16), or halogen (group 17) atom; or a derivative thereof wherein at least one H radical is replaced with a C1-C8 alkyl, a C6-C10 aryl or a heteroaryl radical. Examples of group 15 onium cations are ammonium (NH4+), phosphonium (PH4+) and arsonium (AsH4+). Thus, onium cations can also be considered as monovalent cations. Preferred organic onium cations are nitrogen-comprising onium cations such as pyrrolidinium, imidazolium, imidazolinium ions. The terms “C1-C8 alkyl” and “C6-C10 aryl” have the meaning described above. The term “heteroaryl” refers to an aromatic monocyclic or bicyclic system containing from 5 to 10 ring atoms containing one or more, specifically one, two or three ring heteroatoms independently selected from O, N and S, and the remaining ring atoms being carbon.
In another embodiment, the cation M is an organometallic cation. This can be monovalent, divalent, trivalent or polyvalent. The organometallic cation can be chosen from metalloceniums. For example, mention may be made of the cations derived from ferrocene (i.e. ferrocenium ion), from titanocene, from zirconocene, from an indocenium or from an arene metallocenium. It can also be chosen from metal cations coordinated by atoms such as O, S, Se, N, P or As, borne by organic molecules, in particular in the form of carbonyl, phosphine or porphyrine ligands optionally containing chirality. M can also be a metal cation bearing alkyl groups, such as those containing from 1 to 10 carbon atoms, for example a trialkylsilyl or dialkylstannyl derivative; in this case, M is linked to the anion [R1—S(O)2—N−—S(O)(R2)—N—S(O)2—R3] via a very labile covalent bond and the compound behaves like a salt. The cation M can also be the cationic oxidized form of methylzinc, phenylmercury, trialkyltin or trialkyllead (wherein alkyl means “C1-C8 alkyl” as defined above), chloro[ethylenebis(indenyl)]zirconium(IV) or tetrakis-(acetonitrile)palladium(II) cations.
In a particularly preferred embodiment, the cation M is a polyonium cation. A polyonium cation can be introduced by the cation exchange step after step b). The cation exchange step can be carried out via standard methods known in the art for cation exchange, for example by dissolving the compound I with a polyonium halide in the same solvent (e.g. water) and let them react until completion. In a preferred embodiment the polyonium cation is a polyammonium, polypyrrolidonium, polyimidazolium, polyimidazolinium cation, preferably a polyammonium, polyimidazolium, or polyimidazolinium cation.
In a preferred embodiment, the polypyrrolidonium cation has the following general formula:
wherein each R is independently alkyl, alkenyl, aryl, or alkylene oxide, wherein these terms have the meaning described above; and wherein y denotes the number of repeating onium ion units comprised in the polyonium. Preferably, the alkyl and alkenyl are respectively a C1-C12 alkyl and a C2-C12 alkenyl. Preferably, the alkylene oxide is ethylene oxide or propylene oxide; preferably in the alkylene oxide n is 2, even more preferably n is 1. In a preferred embodiment, the polypyrrolidonium cation is polyDADMA, that is polydiallyldimethylammonium.
In another preferred embodiment, the polyimidazolium cation is one wherein the imidazolium cations do not form part of the polyimidazolium backbone, but are rather comprised in sidechains thereof.
In a particular embodiment, the polyimidazolium cation may have one of the following general formulas:
where each R is independently alkyl, alkenyl, aryl, or alkylene oxide, wherein these terms have the meaning described above; X is a spacer corresponding to an alkylene (preferably a C1-C6 alkylene), a phenylene (—C6H4— optionally with ortho, meta or para substitution on the aromatic ring) or a —C(═O)O— group; and y denotes the number of repeating onium ion units comprised in the polyonium. Preferably, the polyimidazolium cation is
wherein R, X and y are defined as above.
In another preferred embodiment, the polyimidazolinium cation is selected from one of the following structures:
wherein each R, X and y are defined as above for polyimidazoliums.
The anion of the salt of formula (I) has two R fragments, R1 and R2, which are independently selected from —Y, —OY, —SY, —NY2 and halogen.
In one embodiment, R1 and R2 are identical. In another embodiment, R1 and R2 differ from each other.
In one embodiment, both R1 and R2 are independently selected from —Y, —OY, —SY, —NY2. In another embodiment, one of R1 and R2 is a halogen, preferably F, and the other is selected from —Y, —OY, —SY, —NY2, preferably from —Y and —NY2. In another embodiment, both R1 and R2 are halogen, preferably both are F.
In another embodiment, R1 and R2 are independently selected from —Y, —NY2 and halogen.
In another embodiment, R1 and R2 are independently selected from —Y and —NY2. In another preferred embodiment, at least one of R1 and R2 is —Y. More preferably, both R1 and R2 are —Y.
In another preferred embodiment, at least one of R1 and R2 is —NY2. More preferably, both R1 and R2 are —NY2.
In a preferred embodiment, Y represents an organic radical selected from alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, optionally substituted with at least a substituent selected from the group consisting of F, Cl, Br, I, —CN, —OR′, —SR′, —NR′2, wherein each R′ is independently selected from H, alkyl, alkylene oxide or alkylene imine.
In a more preferred embodiment, Y represents an organic radical selected from alkyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, optionally substituted with at least a substituent selected from the group consisting of F, Cl, Br, I, —CN, —OR′, —SR′, —NR′2, wherein each R′ is independently selected from H, alkyl, alkylene oxide or alkylene imine.
In a preferred embodiment, the organic radical is substituted with at least one F, Cl, Br or I. The substitution can occur at any position of the aliphatic chain or aromatic ring present in the radical, meaning that at least one aliphatic or aromatic C—H group is substituted by F, Cl, Br or I. More preferably, Y represents an organic radical selected from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, i.e. any aliphatic or aromatic C-H present in the organic radical is partially or completely substituted with F atoms.
In one embodiment, at least one of the groups R1 and R2 is independently selected from —Y, —OY, —SY, —NY2.
In a preferred embodiment, at least one of R1 and R2 is —Y. More preferably, Y represents an organic radical chosen from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In another preferred embodiment, at least one of R1 and R2 is —NY2. More preferably, Y represents an organic radical chosen from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In a preferred embodiment, Y represents an organic radical as defined above. In a more preferred embodiment, the organic radical is optionally substituted with at least one F, Cl, Br or I. More preferably, the organic radical is optionally fluorinated or perfluorinated, i.e. the H atoms at any aliphatic chain or aromatic ring present in the radical are partially or completely substituted by F atoms. In an embodiment, the organic radical is fluorinated or perfluorinated. In a preferred embodiment, at least one of the groups R1 and R2 is F and the remainder, if any, is —Y, wherein Y is as described elsewhere herein. More preferably, at least one of the groups R1 and R2 is F and the remainder is selected from —Y, wherein Y represents an organic radical chosen from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In another preferred embodiment, at least one of the groups R1 and R2 is F and the remainder, if any, is —NY2, wherein Y is as described elsewhere herein. More preferably, at least one of the groups R1 and R2 is F and the remainder, if any, is —Y, wherein Y represents an organic radical chosen from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In a preferred embodiment, at least one of the groups R1 and R2 is F and the remainder, if any, is independently selected from —OY, —SY, —NY2, preferably from —OY and/or —NY2, wherein Y is as described elsewhere herein. More preferably, Y is alkyl, alkenyl, alkynyl or alkylene oxide.
In a preferred embodiment, at least one of the groups R1 and R2 is F and the remainder, if any, is independently selected from —Y, —OY, —SY, —NY2, wherein Y for —Y is selected from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably selected from fluorinated or perfluorinated alkyl; and Y for —OY, —SY, —NY2 is alkyl, alkenyl, alkynyl or alkylene oxide.
In a preferred embodiment:
In a preferred embodiment:
In an embodiment, in the ionic compound of formula I as defined above, Y groups are optionally substituted. In another embodiment, they are substituted. Substitution is preferably at any aliphatic or aromatic C—H bond present in the organic radical.
In a specific embodiment, each Y independently represents an alkyl radical as described above which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3. In a more specific embodiment, at least one of R1 and R2 is F and Y at any —Y group at the remainder of R1 and R2 is selected from an alkyl radical which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3.
In a more specific embodiment, at least one of R1 and R2 is F and the remainder of R1 and R2, if any, is selected from —Y, wherein Y is an alkyl radical which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3.
Examples of perfluorinated radicals Y are —CF3, —CF2CF3, —CF2(CF2)nCF3 (n=1 to 7), —CF(CF3)2, —CF2CF(CF3)2, —CF(CF3)(CF2)nCF3 (n=1 to 5), —CF2CF(CF3)(CF2)nCF3 (n=1 to 4), —CF═CF2, —CF═CFCF3, —CF2CF═CF2, —CF═C(CF3)2, —CF═CFCF2CF3, —CF2CF═CF2CF3, —CF2CF2CF═CF2, —C≡CCF3, —CF2C≡CF, —C≡CCF2CF3, —CF2CF2C≡CF, —C(O)CF3, —C(O)(CF2)nCF3 (n=1 to 6), —C(O)C6F5, —C(O)C6F4CF3, —C6F5, —C6F4CF3, —C6F4CF2CF3, —C6F3(CF3)CF3 (all ortho, meta and para isomers), —CF2C6F5, —CF2CF2C6F5, —CF2C6F4CF2 (all ortho, meta and para isomers).
In another preferred embodiment, at least one of the groups R1 and R2 is F and the remainder, if any, is a group —Y, wherein Y is a polymeric group comprising repeating units selected from alkylene oxide, alkylene imine, styrene, acrylate, maleimide, phosphazene, siloxane, vinyl alcohol, vinyl amine or mixtures thereof, preferably the polymeric group comprises repeating units selected from alkylene oxide, alkylene imine, acrylate, maleimide, phosphazene, siloxane, vinyl alcohol, vinyl amine or mixtures thereof, more preferably the polymeric group comprises repeating units selected from alkylene oxide, acrylate or maleimide repeating units. These repeating units have the same meaning and particular embodiments as provided for the conductive polymer below. In another preferred embodiment, Y is a polymeric group comprising repeating units of alkylene oxide or alkylene imine, more preferably of alkylene oxide. The term “acrylate” has to be understood in a broad sense as including derivatives such as alkylacrylates and alkyl esters thereof, preferably methylmethacrylate.
In a preferred embodiment, the alkylene oxide is ethylene oxide, propylene oxide or a copolymer of these two, wherein the copolymer preferably has the following structure:
wherein x and y subscripts are positive integers corresponding to a number of repeating units in the polymeric chain and the sum of x and y preferably amounts to at least 100 or at least 1000, and preferably up to 115.000.
Examples of repeating units or monomers are shown in parentheses below (the bond outside the parentheses does not define a methyl group but denotes a bond to the rest of the polymer, such as to other repeating units, to terminal groups, to the rest of the compound of formula I, or to the linker):
wherein R is alkyl as defined elsewhere throughout the text and x and y subscripts are positive integers corresponding to a number of repeating units in the polymeric chain and is preferably at least 100 or at least 1000, and preferably up to 115.000. The repeating unit of the polymeric group may be connected to the sulfur atoms of the compounds of formula via carbon atom or via a heteroatom (O, N, P or Si). The polymeric groups could be considered as a particular case of Y being a substituted aliphatic chain bearing alkylene oxide, alkylene imine, acrylate, maleimide, vinyl alcohol, vinyl amine repeating units. These polymeric groups could be obtained from the corresponding sulfonamide originally bearing the repeating unit or from a sulfonamide that can be later modified to introduce the repeating unit. For example, a sulfonamide with the formula NH2—SO2(CH2)n—OY′ or NH2—SO2—(CH2)n—NY′2 where Y′ is a protecting group, can be later substituted by an alternative Y, which is a polymeric group. (CH2)n in the previous formula aims to indicate that OY′ and NY′2 can be directly linked to the sulfur (n=0) or there might be a linker in between (n=1, 2, 3, etc.). More details were provided above for alkylene and alkylene imine substitution. Another strategy includes the substitution of a sulphonamide bearing a S-halogen bond with an alternative Y, which is a polymeric group. Such strategies are well documented in literature, for example Zhang et al., Chem. Soc. Rev., 2017 February 6;46 (3): 797-815) describes the following two strategies to form conductive polymers (paragraph 2):
Terminal group(s) comprised in the polymeric group depend on the type of repeating unit that terminates the polymer chain and the type of reaction employed for polymerization. In an embodiment, the terminal group(s) are H or alkyl as described above, preferably H or methyl, more preferably methyl.
In a particular embodiment, the polymer group has a molecular weight of between 50 Dalton and 5000000 Dalton (preferably measured by gel-permeation chromatography).
The anion of the salt of formula (I) has also a E fragment attached to the central S atom, which is selected from F; Br; CI; I; —N(R4)(R5), wherein R4 and R5 are independently selected from H, an alkyl and an ethylene oxide chain having from 1 to 5 repeating units of ethylene oxide; an alkyl optionally substituted with at least one F, 13 N(R6)(R7) or OR8, wherein R6, R7 and R8 are independently selected from H and alkyl; and an arylalkenyl. Preferably, the ethylene oxide chain has from 1 to 3 repeating units of ethylene oxide.
In another preferred embodiment, E is selected from F; Br; Cl; I; —N(R4)(R5), wherein R4 and R5 are independently selected from H, an alkyl and an ethylene oxide chain having from 1 to 5 repeating units of ethylene oxide; and an alkyl optionally substituted with at least one F, N (R6)(R7) or OR8, wherein R6, R7 and R8 are independently selected from H and alkyl.
In another preferred embodiment, E is selected from F; an alkyl optionally substituted with at least one F; and N(R4)(R5), wherein R4 and R5 are independently selected from H, an alkyl and an ethylene oxide chain having from 1 to 5 repeating units of ethylene oxide.
More preferably, E is selected from F, an alkyl substituted with at least one F, and N(R4)(R5), wherein R4 and R5 are independently selected from an ethylene oxide chain having from 1 to 3 repeating units of ethylene oxide. Even more preferable, E is F or CF3, and much more preferable E is F.
In a preferred embodiment, the method of the invention affords an ionic compound of formula I, wherein E is F or CF3, and the groups R1 and R2 are independently selected from —Y, —OY and NY2, preferably from —Y, wherein Y is as described elsewhere herein. Preferably, Y is a partially fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl.
In a preferred embodiment, the method of the invention affords an ionic compound of formula I, wherein E is F or CF3, and the groups R1 and R2 are independently selected from —Y and —OY, preferably from —OY, wherein Y is as described elsewhere herein. More preferably, Y is alkyl, alkenyl, alkynyl or alkylene oxide.
In a preferred embodiment, the method of the invention affords an ionic compound of formula I, wherein E is F or CF3, and the groups R1 and R2 are independently selected from —Y and NY2, preferably from —NY2, wherein Y is as described elsewhere herein. More preferably, Y is alkyl, alkenyl, alkynyl or alkylene oxide.
In another preferred embodiment, the method of the invention affords an ionic compound of formula I, wherein E is F or CF3, and at least one of R1 and R2 is halogen, preferably F, and the remaining is selected from —Y and 13 OY, preferably from 13 Y, wherein Y is as described elsewhere herein. In another preferred embodiment, E is F and R1 and R2 are a halogen, preferably F.
In another embodiment, the method of the invention affords an ionic compound of formula I, wherein M is Li30 , Na+ or K+;
E is F and the groups R1 and R2 are independently selected from 13 Y and 13 OY, preferably from —Y, wherein Y represents an organic radical, selected from alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, optionally substituted with at least one F, Cl, Br or I, more preferably any aliphatic or aromatic C—H present in the radical is partially fluorinated or perfluorinated.
In a most preferred embodiment, the method of the invention affords the ionic compound of formula I, wherein E is F and:
In another embodiment, R1 and R2 are the same.
In a preferred embodiment:
In another embodiment, R1 and R2 are the same and Y is an alkyl radical comprising from 1 to 4 carbon atoms which is partially fluorinated or perfluorinated, preferably the alkyl radical is perfluorinated methyl (CF3).
In another embodiment, R1 is different from R2.
Step a) of the process of the invention comprises the reaction of a N-(sulfinyl)sulfonamide of formula (II) R1SO2N═S═O with a sulphonamide salt of formula (III) R2SO2N(M)m, wherein
When M is a proton, the reaction can still take place however it may require the presence of a base. Suitable bases for carrying out the reaction between compounds of formula (II) and (III) (when M is proton) are hydroxide and hydrides of alkali and alkaline earth metals, non-nucleophilic bases, as tertiary amines, amides of alkali and alkaline earth metals or organometallic compounds; preferably suitable bases are non-nucleophilic bases, as tertiary amines, amides of alkali and alkaline earth metals or organometallic compounds.
The reaction between a compound of formula (II) and a compound of formula (III) generates a dianionic compound of formula (IV) [R1SO2—N31 —S(═O)—N−—SO2R2][M]m as defined above.
Compounds of formula (II) R1SO2N═S═O can be obtained by reaction of the corresponding sulphonamide R1SO2NH2 with SOCl2 (for example, J. Chem. Soc., Perkin Trams. 1, 2002, 1887-1889 and references therein).
Sulphonamide salts of formula (III) R2SO2N(M)m can be obtained by reaction of the corresponding R2SO2NH2 with a suitable base able to extract the protons of the amino group in an aprotic solvent. Examples of suitable bases include an alkali or alkaline earth metal hydroxide, alkoxide, carbonate, hydride, amide, such as sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, cesium carbonate or potassium hydride, while examples of suitable aprotic solvents include THF, diethyl ether, methyl tert butyl ether (MTBE), 1,4-dioxane, MeTHF, acetonitrile, dichloromethane, ethyl acetate nitrobenzene, 1,2-dichloroethane or mixtures thereof. The same compound R2SO2NH2 in presence of a base can be used in step a) to react with R1SO2N═S═O. The cation M in both the compound of formula (III) and dianionic sulfonate of formula (IV) can be a number of organic, organometallic and inorganic species that are able to carry one or two positive charges.
Starting sulfonamides R1SO2NH2 and R2SO2NH2 (such as alkyl, aryl and alkylaryl sulphonamides) or sulfonyl chlorides are widely commercially available from different chemical vendors such as Sigma-Aldrich. Alternatively, sulphonamides R1SO2NH2 and R2SO2NH2 can be obtained by the treatment of sulfonyl chloride precursors, i.e., R1SO2Cl and R2SO2Cl, with ammonia, either gas or aqueous solution. Furthermore, sultones and sultams can be used as sulfonyl chloride surrogates to include alkylene oxide and alkylene imine in different ways (see Chapter 19). Strategies to access alkylene oxide/alkylene imine sulfonamides include a) using a sultone/sultam already containing the alkylene oxide/alkylene imine moiety or in a more general way ether/amine moieties in the ring (see Chapter 19, page 855), b) via simple hydrolysis/ammonolysis of sultones/sultams (see Chapter 19, pages 819 and 862), or c) via addition of aliphatic nucleophiles bearing the desired alkylene oxide/alkylene imine moiety (see Chapter 19, pages 835-836). Compounds like 1,3-propane sultone and propane sultam are commercially available reagents. Alkenyl and alkynyl derivatives can be prepared from corresponding sulfonyl chloride precursors (a) via ammonolysis of commercial alkenyl/alkynyl sulfonyl chlorides; b) via addition of Grignard reagents to sulfuryl chloride, see WO2010038465 A1 2010-04. In the particular case of R1 and/or R2 equal to OY, SY and NY2 and Y═H, the alcohol, thiol or amine can be protected prior to avoid any undesired reactions of the sulfinyl sulfonamide, and then deprotected after obtaining compound of Formula I. An easy approach to get the sulfonamides would be to react sulfamoyl chloride with the corresponding protected alcohol, thiol or amine and subsequently deprotection of the alcohol, thiol or amine would follow according to general protection/deprotection strategies (Protecting Groups, Philip Kocienski, ISBN: 3-13-137003-3, Georg Thieme Verlag Stuttgart or Protective Groups in Organic Synthesis, Theodora W. Greene, Peter G. M. Wuts, 4th Edition, 2006, ISBN: 978-0-471-69754-1, Wiley).
In a preferred embodiment, M is an alkali metal, that is, a metal of the group 1 of the periodic table that forms a monovalent cation M+. In a preferred embodiment, M is an alkali metal selected from Li+, Na+, K+ and Cs+. More preferred alkali metals are Li+, Na+ and K+. Even more preferably, the alkali metal is K+. When M is an alkali metal, subscript m is equal to 2.
In another embodiment, M is an alkaline earth metal, that is, a metal of the group 2 of the periodic table that forms a divalent metal cation M2+. In a preferred embodiment, the alkaline earth metal is selected from Mg2+, Ca2+ and Ba2+. When M is an alkaline earth metal, subscript m is equal to 1.
In another embodiment, M is a transition metal with a valency of 1 or 2. In a preferred embodiment, M is a transition metal selected from the group consisting of Cu2+, Zn2+, Fe2+ and subscript m is equal to 1.
In a preferred embodiment, the cation M is selected from the group of metal cations consisting of K+, Li+, Na+, Cs+, Mg2+, Ca2+, Ba2+, Cu2+, Zn2+, Fe2+ preferably the cation is K+.
In another embodiment, the cation M is an organic onium cation as defined above.
In another embodiment, the cation M is an organometallic cation as defined elsewhere herein.
In another particular embodiment, the R fragments, R1 and R2 are as defined elsewhere herein.
In a particular embodiment, the reaction between the N-(sulfinyl)sulfonamide of formula (II) and the sulphonamide salt of (III) is performed by adding R1SO2N═S═O dissolved in a suitable organic solvent to a suspension of R2SO2N(M)m suspended in the same or in a different organic solvent. In a preferred embodiment, the organic solvent is the same. Suitable solvents, both for dissolution of compound (II) and for a suspension of compound (III), are aprotic polar solvents such as THF, diethyl ether, methyl tert butyl ether (MTBE), dioxane, MeTHF, acetonitrile, dichloromethane, ethyl acetate or a combination thereof. Preferably, the solvent is a combination of THF with any of the aprotic polar solvents above. Even more preferably the solvent is THF.
The resulting mixture is let to react until complete conversion, typically for 20 minutes to 10 hours, more preferably for 1 hour.
The obtained compound is a dianionic compound of formula (IV) wherein the central sulfur atom has an oxidation state of (IV), thus rendering said intermediate compound a versatile synthon for oxidation reactions. Indeed, the dianionic compound of formula (IV) can react with electrophilic species to afford the corresponding sulfonate compounds of formula (I) where the central sulfur atom is in its highest oxidation state, S (VI).
Compound of formula (IV) can be purified, isolated and then used for the subsequent steps.
However, in a preferred embodiment of the present invention, step a) and step b) are performed in a one-pot manner. In this case, a purification step of the compound of formula (IV) is avoided, thus rendering the overall process less time-consuming and wasteful.
As said earlier, the compound of formula (IV) [R1SO2—N−—S(═O)—N−—SO2R2][M]m obtained following step a) as described above, is susceptible of reaction with an appropriate electrophilic precursor at the central sulfur atom.
In an embodiment, the compound of formula (IV) is reacted with a reagent source of a E group as defined above. A reagent source of a E group can be understood as any neutral or charged reagent that may release en electrophilic group E able to accept an electron pair (from a nucleophile or electron-rich atom) to form a new bond. Such reagents suit the electron-rich character of the central sulfur atom in the compound of formula (IV) readily leading to the formation of a new E—S bond where the sulfur atom is in a VI oxidation state.
Typical reagents suitable to react with compound IV are fluorination reagents, chlorination reagents, bromination reagents, iodination reagents, alkylation reagents including fluoroalkylation reagents, and amination reagents as defined earlier in the text.
In a preferred embodiment, the reagent source of the E group is an reagent selected from F-TEDA, NFSI, N-fluoropyridinium tetrafluoroborate, NBS, NCS, NIS, ClN(R4)(R5) (wherein wherein R4 and R5 are independently selected from H, an alkyl and an ethylene oxide chain having from 1 to 5 repeating units of ethylene oxide) or a trifluoromethylation reagent selected from Togni reagents (I and II), Langlois reagent (CF3SO2Na) and Umemoto's reagent. More preferably is F-TEDA.
In an embodiment, the reagent source of an E group is added neat.
In another embodiment, the reagent source of a E group is first dissolved in an organic solvent or in a mixture of organic solvents and then added to the solution of compound of formula (IV) resulting from step a) as described above.
In another embodiment, an organic solvent or a mixture of organic solvents is first added to the solution of compound of formula (IV), then the reagent source of a E group is added.
In a preferred embodiment, a mixture of THF and HFIP (hexafluoro-2-propanol) is first added to the solution of compound of formula (IV), then the reagent source of a E group is added. In a more preferred embodiment the ratio THF:HFIP is comprised between 10:1 to 1:10.
In another preferred embodiment, the reaction is let to react for 30 min to 48 hours until completion, preferably for 1 to 6 hours.
After conducting step b), the reaction provides an ionic compound of formula (I) as defined elsewhere above.
In an embodiment, the obtained ionic compound of formula (I) is subjected to purification. This step ensures the separation of said ionic compound from possible by-products in the reaction medium. In an embodiment, the purification of the ionic compound of formula (I) is performed by firstly evaporating the solvent and then extracting with aqueous acid and organic solvent.
Solvent evaporation can be performed by several techniques known to the person skilled in the art, for example by heating up the solution to a suitable temperature, applying reduced pressure or by a combination of heating and reduced pressure. A skilled person would be able to find the optimal pressure and temperature values for the evaporation of the solvent. In another embodiment, the extraction with aqueous acid and organic solvent is performed at least one time, at least two times or at least three times.
In another embodiment, the collected organic fractions from the at least one, at least two or at least three extractions is removed under reduced pressure.
The method of the present invention optionally comprise an additional step which allows functional groups interconversion to access other desired ionic compounds of formula (I) starting from the route as described herein above.
This is particularly the case wherein fragment E of the ionic compound of formula (I), obtained after conducting step b), is a fluorine atom.
Thus, in one embodiment, when E is a fluorine atom in the formula (I) obtained in step b), the process of the invention may further comprises a step wherein said fluorine atom is replaced by other nucleophile by a nucleophilic substitution reaction as taught in the textbook “The Chemistry of Sulfonic Acids, Esters, and Their Derivatives” (chapters 11, 21 and 22). More particularly, said fluorine atom is replaced by an alkyl radical or by a radical N(R4)(R5), wherein R4 and R5 are as defined above, by reacting said salt of formula (I) with an alkylation reagent or an amination reagent. The starting fluoride (E=F) would be equivalent to a sulfonyl halide, to a halosulfonic acid derivative, or to a sulphamic acid derivative. The reactivity of these compounds is well known and described in textbooks, such as “The Chemistry of Sulfonic Acids, Esters, and Their Derivatives” (DOI: 10.1002/0470034394, Chapters 11, 21 and 22). Electron-withdrawing groups attached to the sulfur (VI) atom bearing the E group would make such E group more susceptible to nucleophilic attack, so it would be possible to substitute a fluoride, a chloride, a bromide or a iodine by another nucleophile. Nucleophilic hydrocarbons (e.g. TMS-alkanes) reacting with halosulfonic acid derivatives to afford sulphamic acid derivatives belong to common general knowledge. Additionally, O—, S—and N—containing compounds can also act as nucleophiles and a skilled person would routinely use them to replace a halide and obtain O—, S—and N—substituted products.
Thus, said reagents should be able to withdraw fluorine atoms from the E position and replace them with alkyl. In a particular embodiment, said reagents are organolithium and organomagnesium compounds, such as methyl lithium, phenyl magnesium bromide; or amino groups, such as ethyl-methyl amine, (methoxy methyl).(ethyl) amine. Such substitution should take place in basic conditions, in the presence of a base, such as secondary or tertiary amine, and at temperatures from 20 to 100° C. from 1 h to 48 h.
The ionic compound of formula (I) to be obtained according to the method of the invention contemplates the possibility of M being a trivalent cation or a polyonium cation. However, in the compound of formula (I) obtained after step (b), M is a monovalent cation or a divalent cation, so that an additional step is necessary to replace the M resulting from step (b) by a trivalent cation or polyonium cation.
Therefore, for this particular embodiment, the process of the invention further comprises a cation exchange reaction from the salt of formula (I) resulting from step b) to replace the monovalent or divalent cation M by a trivalent cation or a polyonium cation. Said monovalent or divalent cation is selected from ions of alkali metals, of alkaline earth metals, of transition metals, of rare-earth metals, an organic onium or a monovalent or divalent organometallic cation.
This cation exchange step can be carried out by widely known methods resulting in a compound of formula (I) where M is a trivalent cation or a polyonium cation.
In an embodiment, the cation exchange reaction is performed by dissolving the compound of formula (I) obtained after conducting step b) in a solvent, such as water, and then reacting it with a suitable salt having a trivalent cation. In a preferred embodiment, the salt is an aluminium salt, more preferably is Al2(SO4)3.
In an embodiment, the cation exchange reaction is performed by dissolving the compound of formula (I) obtained after conducting step b) in a solvent, and then reacting it with a suitable metal, such as aluminum. In a preferred embodiment, the metal is aluminium foil.
In a preferred embodiment, the trivalent cation is selected from Al3+, Fe3+, Re3+, Sc3+, Cr3+, Mn3+, preferably is Al3+.
In another embodiment of the process of the invention, and irrespective of the cation M of the ionic compound of formula (I) obtained after conducting step b), said ionic compound of formula (I) can also be optionally subjected to a cation exchange step. In this embodiment, the ionic compound or salt of formula (I) is converted to another desired salt of formula (I′) [R1SO2—N−—S(═O)(E)=N—SO2R2]n[M′], wherein M′ is different from M, via standard methods known in the art for cation exchange. When M is replaced by M′ which is a different monovalent or divalent cation, such cation is selected from the lists of monovalent and divalent cations already mentioned above.
In a preferred embodiment, M′ is an alkali metal, more preferably is Li+. In an embodiment, in the cation exchange reaction M is K+ and is exchanged by M′ being Li+.
In another embodiment, M′ is a polyonium cation as defined elsewhere herein.
It would be evident to a skilled person that the charge of the polyonium is compensated by a sufficient number of anions in the resulting ionic compound of formula (I′) (for example, if the polyonium has a charge of +10, then the subscript n in formula I will be 10 and the resulting ionic compound will be overall neutral).
In a preferred embodiment, the cation exchange reaction is performed to obtain an ionic compound of formula I′, wherein M′ is Li+, Na+ or a polyonium cation. In an embodiment, M′ is Li+. In another embodiment, M′ is a polyonium cation.
The cation exchange step can be carried out by widely known methods such as that described for example in Heng Zhang et al., Angew. Chem. Int. Ed., 2019, 131(23), 7911-7916).
In a particular embodiment, the cation exchange reaction is performed by dissolving the compound of formula (I) in a suitable solvent and then reacting it with a suitable salt to afford a salt of formula [R1SO2—N−—S(═O)(E)=N—SO2R2][M′].
In a particular embodiment, the cation exchange reaction is performed by dissolving the compound of formula (I), wherein M is not Li+, in water and then reacting it with a suitable lithium salt to afford a salt of formula [R1SO2—N−—S(═O)(E)=N—SO2R2][Li+]. In a preferred embodiment, the lithium salt is lithium carbonate.
In another embodiment, the cation exchange reaction is performed by dissolving the compound of formula (I) in water and then reacting it with a polyonium salt. In a preferred embodiment, the polyonium salt is a polyonium halide.
In a preferred embodiment, the cation exchange reaction takes place at a temperature between 0° C. and 40° C., preferably at a temperature between 20° C. and 30° C., more preferably at room temperature. In an embodiment, the reaction mixture is stirred for a sufficient time for the cation exchange to take place, preferably at least 5 min, at least 30 min, at least 1 hour, at least 2 hours, at least 4 hours, at least 8 hours, at least 16 hours and no longer than 24 hours. In another embodiment, the water solvent is subsequently removed under vacuum.
In another embodiment, the salt [R1SO2—N−—S(═O)(E)=N—SO2R2]n[M′] obtained after cation exchange is recrystallized. In a preferred embodiment, said salt is [R1SO2—N−—S(═O)(E)=N—SO2R2][Li+] and is recrystallized from acetonitrile.
The dianionic compound intermediate of formula (IV):
as obtained from step a) and as defined above constitutes another aspect of the present invention.
In a preferred embodiment, M is an alkali metal, that is, a metal of the group 1 of the periodic table that forms a monovalent cation M+. In a preferred embodiment, M is an alkali metal chosen from Li+, Na+, K+ and Cs+. More preferred alkali metals are Li+, Na+ and K+. Even more preferably, the alkali metal is Li+.
In another embodiment, M is an alkaline earth metal, that is, a metal of the group 2 of the periodic table that forms a divalent metal cation M2+. In a preferred embodiment, the alkaline earth metal is selected from Mg2+, Ca2+ and Ba2+.
In another embodiment, M is a transition metal selected from the group consisting of Cu2+, Zn2+ and Fe2+.
In a preferred embodiment, the cation M is selected from the group of metal cations consisting of K+, Li+, Na+, Cs+, Mg2+, Ca2+, Ba2+, Cu2+, Zn2+ and Fe2+.
In a particular embodiment, the dianionic compound intermediate of formula (IV) is characterized by M being a metal cation selected from K+, Lit, Na+, Cs+, preferably is K+.
In a particular embodiment, the dianionic compound intermediate of formula (IV) is characterized in that R1 and R2 are independently selected from:
In one embodiment, both R1 and R2 are independently selected from —Y, —OY, —SY, —NY2. In another embodiment, one of R1 and R2 is a halogen, preferably F, and the other is selected from —Y, —OY, —SY, 13 NY2. In another embodiment, both R1 and R2 are halogen, preferably both are F.
In another embodiment, R1 and R2 are independently selected from —Y, —NY2 and halogen.
In another embodiment, R1 and R2 are independently selected from —Y and —NY2.
In another preferred embodiment, at least one of R1 and R2 is —Y. More preferably, both R1 and R2 are —Y.
In another preferred embodiment, at least one of R1 and R2 is —NY2. More preferably, both R1 and R2 are —NY2.
In a preferred embodiment, Y represents an organic radical as defined above. In a more preferred embodiment, the organic radical is optionally substituted with at least one F, Cl, Br or I. More preferably, the organic radical is optionally fluorinated or perfluorinated, i.e. the H atoms at any aliphatic chain or aromatic ring present in the radical are partially or completely substituted by F atoms. In an embodiment, the organic radical is fluorinated or perfluorinated.
In a preferred embodiment, in the compound of formula (IV) at least one of the groups Rand Ris F and the remainder, if any, is —Y, wherein Y is as described elsewhere herein. More preferably, at one of the groups R1 and R2 is F and the other is —Y, wherein Y represents an organic radical selected from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In another preferred embodiment, in the compound of formula (IV) at least one of the groups R1 and R2 is F and the remainder, if any, is —NY2, wherein Y is as described elsewhere herein. More preferably, at least one of the groups R1 and R2 is F and the remainder, if any, is —Y, wherein Y represents an organic radical chosen from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably Y represents an organic radical chosen from fluorinated or perfluorinated alkyl.
In a preferred embodiment, in the compound of formula (IV) at least one of the groups R1 and R2 is F and the remainder, if any, is selected from —OY, —SY, —NY2, preferably from —OY and/or —NY2, wherein Y is as described elsewhere herein. More preferably, Y is alkyl, alkenyl, alkynyl or alkylene oxide.
In a preferred embodiment, in the compound of formula (IV) at least one of the groups R1 and R2 is F and the remainder, if any, is selected from —Y, —OY, —SY, —NY2, wherein Y for —Y is selected from fluorinated or perfluorinated alkyl, alkenyl, alkynyl, aryl, alkylaryl, arylalkyl, alkylene oxide or alkylene imine, and more preferably selected from fluorinated or perfluorinated alkyl; and Y for —OY, —SY, —NY2 is alkyl, alkenyl, alkynyl or alkylene oxide.
In a preferred embodiment:
In a preferred embodiment:
In an embodiment, in the compound of formula IV as defined above, Y groups are optionally substituted. In another embodiment, they are substituted. Substitution is preferably at any aliphatic or aromatic C—H bond present in the organic radical.
In a specific embodiment, each Y independently represents an alkyl radical as described above which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3.
In a more specific embodiment, at least one of R1 and R2 is F and Y at any —Y group at the remainder of R1 and R2 is selected from an alkyl radical which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3.
In a more specific embodiment, one of R1 and R2 is F and the remainder of R1 and R2 is selected from —Y, wherein Y is an alkyl radical which is fluorinated or perfluorinated, more preferably an alkyl radical comprising from 1 to 4 carbon atoms which is fluorinated or perfluorinated, even more preferably Y represents CF3.
Examples of perfluorinated radicals Y are —CF3, —CF2CF3, —CF2(CF2)nCF3 (n=1 to 7), —CF(CF3)2, —CF2CF(CF3)2, —CF(CF3)(CF2)nCF3 (n=1 to 5), —CF2CF(CF3)(CF2)nCF3 (n=1 to 4), —CF═CF2, —CF═CFCF3, —CF2CF═CF2, —CF═C(CF3)2, —CF═CFCF2CF3, —CF2CF═CF2CF3, —CF2CF2CF═CF2, —C≡CCF3, —CF2C≡CF, —C≡CCF2CF3, —CF2CF2C≡CF, —C(O)CF3, —C(O)(CF2)nCF3 (n=1 to 6), —C(O)C6F5, —C(O)C6F4CF3, —C6F5, —C6F4CF3, —C6F4CF2CF3, —C6F3(CF3)CF3 (all ortho, meta and para isomers), —CF2C6F5, —CF2CF2C6F5, —CF2C6F4CF2 (all ortho, meta and para isomers).
In another embodiment, at least one of R1 and R2 is a halogen, preferably F. In another embodiment, R1 and R2 are both a halogen, preferably F.
In another embodiment, the dianionic intermediate compound of formula (IV) is characterized in that R1 and R2 are the same.
In another embodiment, the dianionic intermediate compound of formula (IV) is characterized in that R1 is different from R2.
In another embodiment, the dianionic intermediate compound of formula (IV) is characterized in that R1 and R2 are the same and Y represents an organic radical selected from alkyl, alkenyl, alkynyl, aryl and alkylaryl radicals, which are partially fluorinated or perfluorinated.
In another embodiment, the dianionic intermediate compound of formula (IV) is characterized in that R1 and R2 are the same and Y is an alkyl radical comprising from 1 to 4 carbon atoms which is partially fluorinated or perfluorinated, preferably the alkyl radical is perfluorinated methyl (CF3).
In a most preferred embodiment, the dianionic intermediate compound of formula (IV) is:
The dianionic intermediate compound of formula (IV) is a versatile synthon that can be used in electrophilic oxidation and oxidative addition reactions.
The invention also refers to a dianion of formula:
wherein R1 and R2 are as defined above for the compound of formula (IV).
Further embodiments of the invention include:
The structures of salt 1 (LisFTFSI) is shown below:
All reagents for the synthesis of (S-fluoro-N-((trifluoromethyl)sulfonyl)sulfonimidoyl)((trifluoromethyl)sulfonyl)amide (LisFTFSI) were purchased from Sigma-Aldrich and used as received. Solvents were distilled and dried prior to use. Specifically, LisFTFSI was prepared in a one-pot fashion by reaction of a sulphonamide salt with an N-(sulfinyl)sulfonamide and subsequent oxidation with an electrophilic fluorine source. More specifically, the synthetic route to lithium (S-fluoro-N-((trifluoromethyl)sulfonyl)sulfonimidoyl)((trifluoromethyl)sulfonyl)amide (LisFTFSI) is illustrated in the scheme below.
Trifluoromethanesulfonylamide dipotassium salt was obtained by reacting potassium tert-butoxide, KOtBu (7.6 g, 2.5 eq., 68.1 mmol) with trifluoromethanesulfonamide (4.8 g, 32.4 mmol) in THF (70 mL) under reflux for 16 h. The obtained white solid was filtered and washed with abundant THF to yield pure dipotassium salt.
A solution of N-(sulfinyl)trifluoromethanesulfonamide (1 eq, 1.8 mmol), obtained as described in Journal of Fluorine Chemistry, 60 (1993) 283-288, in THF (2.2 mL) was added to a suspension of trifluoromethanesulfonylamide dipotassium salt (0.69 g, 1.5 eq, 2.7 mmol) in THF (2.2 mL) at −20° C. The mixture was stirred and allowed to reach room temperature until complete conversion was achieved as confirmed by 19F-NMR. A mixture of THF:HFIP (hexafluoro-2-propanol) 6.5:1 (12.1 mL) was added followed by 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) (1.5 eq, 2.7 mmol), also called F-TEDA. The reaction mixture was stirred until no further evolution was observed by 19F-NMR. Then, the solvent was removed under reduced pressure to yield an oil. This oil was taken into water (10 mL) and acidified with H2SO4. The aqueous solution was extracted with diethyl ether (3x15 mL), organic fractions were combined, and solvent was removed under reduced pressure. An aqueous solution of the obtained acid, N,N′-bis((trifluoromethyl)sulfonyl)sulfuramidimidoyl fluoride, was treated with lithium carbonate (0.07 g, 0.5 eq., 0.9 mmol) and the reaction mixture stirred for 16 h at room temperature. Then solvent was removed in vacuo to yield a white solid.
Excess of lithium carbonate was removed by selective dissolution of impurities and recrystallization from acetonitrile. Solvent was removed in vacuo to yield LisFTFSI as a white powder (yield: 4.7 g, 12.9 mmol). 19F-NMR (283 MHz, MeCN-d3) δ (ppm) 69.18-69.04 (m, 1F, F), −79.36 (d, J=3.2 Hz, 6F, 2x CF3). 13C-NMR (75 MHz, MeCN-d3): δ (ppm) 121.7 (qd, J=320.1 Hz, 2.4 Hz, 2x CF3).
Following the general procedure the Lithium (S-fluoro-N-((trifluoromethyl)sulfonyl)sulfonimidoyl)((trifluoromethyl)sulfonyl)amide (LisFTFSI) was synthesized starting from N-(sulfinyl)trifluoromethanesulfonamide (0.39 g, 1.8 mmol) and using 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) (0.96 g, 2.7 mmol), also called F-TEDA, as fluorinating reagent. 19F-NMR (283 MHz, MeCN-d3) δ (ppm) 69.2-69.0 (m, 1F, F), −79.4 (d, J=3.2 Hz, 6F, 2x CF3). 13C-NMR (75 MHz, MeCN-d3): δ (ppm) 121.7 (qd, J=320.1 Hz, 2.4 Hz, 2x CF3).
Following the general procedure in example 1, the lithium (S-trifluoromethyl-N-((trifluoromethyl)sulfonyl)sulfonimidoyl)((trifluoromethyl)sulfonyl)amide was synthesized starting from N-(sulfinyl)trifluoromethanesulfonamide (0.39 g, 1.8 mmol) and using 1-Trifluoromethyl-1,2-benziodoxol-3-(1H)-one (0.85 g, 2.7 mmol), also called Togni reagent II, as trifluoromethylating agent. 19F-NMR (283 MHZ, MeCN-d3) δ (ppm) −79.8 (q, J=1.3 Hz, 3F, CF3), −80.2 (m, 6F, CF3)
Following the general procedure above, lithium (S-methyl-N-((trifluoromethyl)sulfonyl) sulfonimidoyl)((trifluoromethyl)sulfonyl)amide was synthesized starting from N-(sulfinyl)trifluoromethanesulfonamide (0.39 g, 1.8 mmol) and using trimethyloxonium tetrafluoroborate (0,40 g, 2.7 mmol) as methylating agent. 1H-NMR (300 MHz, MeCN-d3) δ (ppm) 3.28 (s, 3H, CH3) 19F-NMR (283 MHz, MeCN-d3) δ (ppm) −78.7 (s, 3F, CF3).
Following the general procedure above, lithium (S-fluoro-N-Following((trifluoromethyl)sulfonyl)sulfonimidoyl)((trifluoromethyl)sulfonyl)amide (LisFTFSI) was synthesized starting from N-(sulfinyl) N,N-dimethylsulfonamide (0.31 g, 1.8 mmol) prepared according to known procedures, i.e. J. Chem. Soc., Perkin Trams. 1, 2002, 1887-1889 and references therein—and using commercial 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2] octane bis(tetrafluoroborate) (0.96 g, 2.7 mmol), also called F-TEDA, as fluorinating reagent. 1H-NMR (300 MHz, MeCN-d3) δ (ppm) 2.81 (s, 6H, CH3) 19F-NMR (283 MHz, MeCN-d3) δ (ppm) 69.1-69.0 (m, 1F, F), −79.2 (d, J=3.2 Hz, 3F, CF3).
Potassium (N-ethyl-N-methyl-N′-((trifluoromethyl)sulfonyl)sulfamidimidoyl)((trifluoromethyl)sulfonyl)amide was obtained as illustrated in the scheme below by the reaction of KsFTFSI with a nucleophilic amine.
To a solution of KsFTFSI (0.1 g, 0.25 mmol) in toluene (3 mL), N-ethylmethylamine (0.05 mL, 1.5 eq, 0.5 mmol) was added at room temperature. The reaction mixture was heated to reflux for 16 hours. After the reaction was completed, the solvent was removed under reduced pressure and the crude was taken into concentrated HCl (aq.). The aqueous phase was extracted with tert-butyl methyl ether (TBME) (3×15 mL), organic fractions were combined, and solvent was removed under reduced pressure. An aqueous solution of the obtained acid, N-((ethyl(methyl)amino)(oxo)((trifluoromethyl)sulfonamido)-λ6-sulfaneylidene)-1,1,1-trifluoromethanesulfonamide was treated with potassium carbonate (0.02 g, 0.5 eq., 0.13 mmol) and the reaction mixture stirred for 16 h at room temperature. Then solvent was removed in vacuo to yield a white solid. Excess of potassium carbonate was removed by selective dissolution of impurities and recrystallization from acetonitrile. Solvent was removed in vacuo to yield a white-off powder. 1H-NMR (300 MHZ, MeCN-d3) δ (ppm) 3.25 (q, J=7.2 Hz, 2H, CH2), 2.84 (s, 3H, CH3), 1.19 (t, J=7.2 Hz, 3H, CH3) 19F-NMR (283 MHz, MeCN-d3) δ (ppm) −79.2 (s, 3F, CF3).
| Number | Date | Country | Kind |
|---|---|---|---|
| 21383222.3 | Dec 2021 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2022/087831 | 12/23/2022 | WO |
