WO2012168458A1 - Zwitterionic compounds useful as catalysts for esterification reactions and processes for their production - Google Patents

Zwitterionic compounds useful as catalysts for esterification reactions and processes for their production Download PDF

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WO2012168458A1
WO2012168458A1 PCT/EP2012/060938 EP2012060938W WO2012168458A1 WO 2012168458 A1 WO2012168458 A1 WO 2012168458A1 EP 2012060938 W EP2012060938 W EP 2012060938W WO 2012168458 A1 WO2012168458 A1 WO 2012168458A1
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acid
group
alkyl
hydrogen
acids
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Jean-Christophe Andre Louis VANHERCK
Robbie VAN DE COEVERING
Koen Jeanne Alfons Van Aken
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Ecosynth Bvba
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0215—Sulfur-containing compounds
    • B01J31/0225—Sulfur-containing compounds comprising sulfonic acid groups or the corresponding salts
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0237—Amines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0237—Amines
    • B01J31/0238—Amines with a primary amino group
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/13—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/14—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton containing amino groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/24—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of a carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/46—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton having the sulfo groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/47—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton having at least one of the sulfo groups bound to a carbon atom of a six-membered aromatic ring being part of a condensed ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C07D213/34—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms
    • C07D213/71—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/36—Sulfur atoms
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/49—Esterification or transesterification
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Definitions

  • the present invention relates to zwitterionic compounds which are useful as catalysts for the preparation of organic esters.
  • the present invention relates to sulfonic acid compounds, such as arenesulfonic acid compounds, including a nitrogen atom in their structure and zwitterionic forms thereof, being useful as catalysts for esterification reactions.
  • the present invention also relates to processes for making such compounds.
  • the present invention also relates to esterification processes catalysed by such zwitterionic compounds.
  • the present invention relates to processes for the preparation of organic esters wherein a zwitterionic catalyst may be recycled and re-used a significant number of times without losing its catalytic activity and/or selectivity.
  • sulfonic compounds such as arenesulfonic compounds, including a nitrogen atom in their structure are already known in the art.
  • This class of aromatic compounds also includes a few sulfanilic acids, i.e. compounds bearing both an amino group and a sulfonic acid group directly attached to the aromatic (phenyl) ring.
  • sulfanilic acids are amphoteric. In the solid state, their sulfonic acid group is able to protonate the amine function, thus forming a zwitterion.
  • ammonium sulfonate form may be favored because an ammonium ion is usually much less acidic than a sulfonic acid.
  • the structure of sulfanilic acids in a solution e.g. an aqueous solution, depends on the pH.
  • Esters are useful in a wide variety of industrial applications, such as plasticizers, lubricants, lubricant additives, lacquer bases, perfumes, cosmetics, foods, coatings, adhesives, resins, fragrances, solvents, extractants, etc.
  • Esterification is one of the most fundamental and important reactions in organic synthesis.
  • the most acceptable method of making an ester is to react an acid with an alcohol in the presence of a catalyst, as shown in the scheme below.
  • This reaction is a well known equilibrium-limited reaction involving reacting a mono-, di- or polycarboxylic acid (or, in suitable cases, a carboxylic acid anhydride) with an alcohol or phenol component.
  • Such an alcohol or henol component can be mono, di- or polyhydric.
  • R l 5 R 2 (Substituted) alkyl or aryl
  • Ester and water can be distilled off together, usually as an azeotropic mixture. On condensation, the mixture separates into an ester and a water phase. To achieve complete evaporation of the ester, water or steam are often added to the reaction mixture.
  • the boiling point of the ester is higher than that of water. In this case, the water is distilled off, frequently as an azeotrope with the alcohol.
  • an entrainer co-solvent
  • the need to remove one of the components or to use an entrainer which often forms binary or ternary azeotropes with other reaction components often complicates the technical set-up and purification.
  • esters from acids and alcohols can also be classified into the following two main categories:
  • the heterogeneous esterification reaction which typically utilizes a cationic ionic exchange resin as catalyst, ameliorates the corrosion and waste disposal problems experienced with the homogeneous processes, and results in simplified separation procedure required between the reaction product and catalysts.
  • these reactions show slower and more complex kinetics.
  • cationic ion-exchange resins typically exhibit relatively poor heat- resistance, and they often lose substantial activity after being subject to heat. Once the catalytic activity of the cationic ion-exchange resins is reduced, it is difficult to be regenerated.
  • reaction conditions are maintained so that all reactants and products are in the gas phase.
  • inorganic materials are used as catalysts which typically exhibit excellent heat resistance and can be easily separated from the reaction products.
  • the gas phase reaction necessitates a relatively large reaction vessel, resulting in large capital investment costs.
  • the high reaction temperature often causes undesired by-products like polymers or oligomers to be produced. In certain instances, the high reaction temperature has even caused the alcohol molecule to be dehydrated to become an ethers or alkene. These side-reactions tend to cause the reaction catalysts to lose their activity and result in operational difficulties.
  • the weak base can be an alkylsulfonate, an imidazole, a trialkylamine, a pyridine or an aniline.
  • sulfamic acid which is hydrolytically unstable, thus making it unsuitable for industrial esterifications.
  • Another class of zwitterionic compounds are sulfanilic acids mentioned herein-above. These have scarcely been used in the preparation of esters. It is known in the art to use p-aminobenzenesulfonic acid (i.e. p-sulfanilic acid) as a catalyst for the esterification reactions of :
  • the catalyst should exhibit high activity, i.e. actively and efficiently promote the esterification reaction within a limited period of time
  • the catalyst should exhibit high selectivity, i.e. avoid the possibility for undesirable side reactions, such as ether formation and dehydration.
  • the catalyst should exhibit sufficient stability under the prevailing operating conditions to be capable of recycling and re-using in the esterification reaction without losing its activity and selectivity
  • the catalyst should also be inexpensive to produce, although an extra production cost may be admissible when a candidate is able to be recycled and re-used significantly more than another catalyst.
  • the suitable candidate should also exhibit sufficient versatility, i.e. be active and selective in the highest possible number of esterification reactions or, otherwise said, its activity and selectivity should depend as little as possible upon the types of acid (or anhydride) and alcohol used in the esterification reactions, and upon the operating conditions used (e.g. temperature, pressure, presence of optional co-catalysts, etc.). All these requirements still to date constitute a stringent need in the field of organic chemistry.
  • the object of the present invention is to avoid the drawbacks of prior art esterification catalysts and processes by providing a new class of esterification catalysts being useful in the performance of processes for the preparation of organic esters.
  • An advantage of the present invention is to provide catalysts and processes for the preparation of organic esters which are environmentally friendly.
  • Another advantage of the present invention is to provide processes for the preparation of organic esters that easily allow catalyst removal.
  • Another advantage of the present invention is to provide processes for the preparation of an ester that allow catalyst multiple reuse.
  • Another advantage of the present invention is to provide esterification processes that are economical and efficient.
  • Another advantage of the present invention is to provide processes for producing esters wherein esterification proceeds rapidly without the formation of by-products originating from the starting alcohols such as, but not limited to, alkenes or ethers.
  • Another advantage of the present invention is to provide novel esterification catalysts having high catalytic activity while effectively avoiding the formation of by-products originating from alcohols.
  • the present invention relates to a process for the preparation of an organic ester, comprising reacting a carboxylic acid or anhydride with an alcohol in the presence of a zwitterionic catalyst, in particular a zwitterionic catalysts as represented by formula 1 below, preferably at a temperature from about 10°C to about 180°C for a time period ranging from about 0.5 to 72 hours, and separating the ester formed from the reaction mixture, provided that said zwitterionic catalyst is not m-sulfanilic acid or p-sulfanilic acid when used as a catalyst for the esterification of :
  • the present invention relates to a novel esterification catalyst being a zwitterionic compound having a ammonium group covalently linked to a sulfonate group optionally by means of a linker provided that said zwitterionic compound is not m-sulfanilic acid or p-sulfanilic acid, especially when used as a catalyst for the esterification of :
  • the ammonium group of the zwitterionic compound of this other embodiment of the present invention should not be a primary ammonium group but may be a secondary ammonium group, a tertiary ammonium group or a quaternary ammonium group.
  • the present invention relates to a process for producing an organic ester including the step of allowing a carboxylic acid or anhydride to react with an alcohol, wherein an zwitterionic compound is used as catalyst, as used herein also referred to as a zwitterionic catalyst, said zwitterionic compound (or zwitterionic catalyst) containing an ammonium cation and a sulfonate anion and including a structural moiety represented by the formula 1 :
  • R'i are independently selected from the group consisting of hydrogen, Ci -4 alkyl, and aryl optionally substituted with one, two or more Ci-4 alkyl substituents;
  • R 4 is independently hydrogen or CMO alkyl
  • R 2 wherein - R 2 is independently hydrogen or CMO alkyl
  • - m is 0 to 4; n is 0 or 1 ;
  • - Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci -4 alkyl, aryl, benzyl, halogen, fluoro-Ci -4 alkyl, nitro, hydroxyl, Ci -4 alkoxy, aryloxy, Ci -4 alkylthio, arylthio and fluoro-Ci -4 alkoxy; or
  • the zwitterionic compound used in the aforementioned compound comprises an aromatic ring between the ammonium cation group and the sulfonate anion group, and corresponds to said compounds of formula 1 , wherein
  • Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci -4 alkyl, aryl, benzyl, halogen, fluoro-Ci -4 alkyl, nitro, hydroxyl, Ci -4 alkoxy, aryloxy, Ci -4 alkylthio, arylthio and fluoro-Ci -4 alkoxy; in particular Ar represents phenyl or naphtyl optionally substituted with Ci -4 alkyl;
  • said zwitterionic compound is not m-sulfanilic acid or p- sulfanilic acid.
  • the zwitterionic compound used in the aforementioned process is defined as in any one of the foregoing embodiments, but with the proviso that said zwitterionic compound is not o- sulfanilic acid, m-sulfanilic acid or p-sulfanilic acid.
  • the zwitterionic compound used in the aforementioned process comprises a heteroaromatic ring, i.e. consists of those compounds of formula 1 , wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; structurally represented by formula 2
  • Het designates a heteroaromatic ring structure containing one to four nitrogen atoms and a total of 5 to 17 ring atoms; in particular containing one nitrogen atom; more in particular Het designates a heterocyclic iminium cation; even more in particular Het designates a pyridinium ring;
  • each R 5 is independently selected from the group consisting of hydrogen, C-1 -4 alkyl, halogen, fluoro-Ci -4 alkyl, nitro, hydroxyl, Ci -4 alkoxy, Ci -4 alkylthio and fluoro-Ci -4 alkoxy; in particular R 5 is hydrogen;
  • each R is independently selected from the group consisting of hydrogen and C-1-10 alkyl; in particular R 4 is hydrogen, and
  • novel esterification catalysts being a zwitterionic compound having an ammonium cation group covalently linked to a sulfonate anion group optionally by means of a linker; said zwitterionic catalysts generally represented by formula 1 wherein;
  • R'i are independently selected from the group consisting of hydrogen, Ci -4 alkyl, and aryl optionally substituted with one, two or more C1-4 alkyl substituents;
  • - R is independently hydrogen or C1-10 alkyl
  • R 2 wherein - R 2 is independently hydrogen or CMO alkyl
  • - m is 0 to 4; n is 0 or 1 ;
  • - Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci -4 alkyl, aryl, benzyl, halogen, fluoro-Ci -4 alkyl, nitro, hydroxyl, Ci -4 alkoxy, aryloxy, Ci -4 alkylthio, arylthio and fluoro-Ci -4 alkoxy; or
  • the single figure schematically shows synthetic routes for producing zwitterionic compounds used as esterification catalysts according to the present invention.
  • Ri , Ri', R , p, and L are defined as for the compounds of formula 1 hereinbefore; and wherein Y represents H, CI, Br, I, paratoluenesulfonate (OTs) or trifluoromethanesulfonate (OTf); and wherein X represents I, Br, CI, OTf or BR 2 with R 2 as defined for the compounds of formula 1 hereinbefore
  • Ci -4 alkyl refers to a straight or branched chain saturated acyclic hydrocarbon monovalent group having from 1 to 4 carbon atoms such as, for example, methyl, ethyl, propyl, n-butyl, 1 -methylethyl (isopropyl), 2-methylpropyl (isobutyl), and 1 ,1 -dimethylethyl (terf-butyl).
  • CMO alkyl refers to a substituting group having from 1 to 10 carbon atoms such as, for example, n-pentyl, isoamyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl.
  • aryl and aromatic ring refer to any mono- or polycyclic aromatic monovalent hydrocarbon group having from 6 up to 30 carbon atoms such as, but not limited to, phenyl, naphthyl, anthracenyl, phenanthracyl, fluoranthenyl, chrysenyl, pyrenyl, biphenylyl, terphenyl, picenyl, indenyl, biphenyl, indacenyl, benzocyclobutenyl, benzocyclooctenyl and the like, including fused benzo-C 4- s cycloalkyl radicals such as, for instance, indanyl, tetrahydronaphtyl, fluorenyl and the like, all of the said groups being optionally substituted with one or more substituents independently selected from the group consisting of halogen, Ci -4 alkyl
  • Ci -4 alkoxy refers to substituent wherein a carbon atom of a Ci -4 alkyl is attached to an oxygen atom through a single bond such as, but not limited to, methoxy, ethoxy, propoxy, n-butoxy, isopropoxy, sec-butoxy, terf-butoxy and the like.
  • Ci -4 alkylthio refers to substituent wherein a carbon atom of a Ci -4 alkyl is attached to an sulfur atom through a single bond such as, but not limited to, methylthio.
  • halogen means any atom selected from the group consisting of fluoro, chloro, bromo and iodo.
  • fluoro Ci -4 alkyl and fluoro Ci -4 alkoxy respectively refer to a Ci -4 alkyl or Ci -4 alkoxy group (such as above defined, including sub-species thereof) in which one or more hydrogen atoms are independently replaced by a corresponding number of fluoro atoms such as, but not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, and the like.
  • heteroaromatic ring refers to any mono- or polycyclic aromatic monovalent group having at least one heteroatom such as nitrogen, oxygen, sulfur or selenium; within the scope of the present invention, the preferred heteroaromatic rings include at least one nitrogen atom and optionally one or more further heteroatoms independently selected from the group consisting of nitrogen, oxygen, sulfur or selenium.
  • the present invention differs in that the charged moieties are structurally integrated within one and the same molecule.
  • the catalytic compound used in the esterification reaction may exist as a zwitterionic form under certain pH conditions, preferably as a zwitterionic compound including both a sulfonate anion and an ammonium or heterocyclic iminium cation.
  • a more particular zwitterionic compound for use in the esterification process of the present invention includes a structural moiety represented by the generic formula 1
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein an aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. L represents the bivalent radical (ai ) wherein n is 1 , and wherein no aliphatic chain is present as a linker between the sulfonate anion or the ammonium cation and said aromatic ring, i.e. m and p are each 0.
  • the sulfonate anion is either in ortho- , metha- or para-position with respect to the ammonium cation, with the proviso that when in this situation the aromatic ring represents phenyl and the ammonium cation is further substituted with an optionally substituted aryl, then the sulfonate anion is in ortho-position with respect to the ammonium cation.
  • the zwitterionic compound of the present invention may still include one or more aliphatic chains either attached to the nitrogen atom of the ammonium cation (i.e. R'i in the aforementioned definition of formula 1), or as a substituent (i.e.
  • the aromatic ring may be monocyclic, e.g. phenyl, or the aromatic ring may be bicyclic, e.g. naphthyl.
  • the sulfonate anion and the ammonium cation may be borne by the same ring (e.g. 2-amino-1 -naphthalenesulfonic acid or 4-amino-1 -naphthalenesulfonic acid) or the sulfonate anion may be borne by one ring and the ammonium cation may be borne by the other ring (e.g. 8-amino-1 -naphthalenesulfonic acid), in a particular embodiment the sulfonate anion is born by one ring and the ammonium cation is borne by the other ring.
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein no aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. those compounds of formula 1 wherein L represents a direct bond, but an aliphatic chain with at least one carbon atom, preferably 2 to 8 carbon atoms, is present between the sulfonate anion and the ammonium cation, i.e. p is from 1 to 8.
  • the zwitterionic compound of the present invention may still include one or more aromatic rings attached to the nitrogen atom of the ammonium cation (i.e. Ri and/or R'i in the aforementioned definition of formula 1 ).
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein no aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. those compounds of formula 1 wherein L represents a direct bond, but further characterized in that the ammonium cation group should not be a primary ammonium group but may be a secondary ammonium group, a tertiary ammonium group or a quaternary ammonium group, i.e. at least one of Ri and/or R'i in the aforementioned definition of formula 1 does not represent hydrogen.
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein an aromatic ring is present between the sulfonate anion and the ammonium cation, and at least an aliphatic chain with 1 to 4 carbon atoms is present as a linker between the sulfonate anion and said aromatic ring and/or between the ammonium cation and said aromatic ring, i.e.
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein Ar represents a phenyl ring; in particular an optionally substituted phenyl ring.
  • the sulfonate anion is in particularly in the ortho-position with respect to the ammonium cation, and an aliphatic chain with one carbon atom (i.e. p is 1 ) is present as a linker between the sulfonate anion and said phenyl ring.
  • the zwitterionic compounds include a heteroaromatic ring, i.e. those compounds of formula 1 wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; such as, but not limited to, a pyridinyl ring or a quinolinyl ring, and the sulfonate anion is directly (i.e. p is 0) or with a covalent linker (i.e. p is 1 to 4) attached to said heteroaromatic ring.
  • a heteroaromatic ring i.e. those compounds of formula 1 wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; such as, but not limited to, a pyridinyl ring or a quinolinyl ring, and the sulfonate anion is directly (i.e. p is 0) or with a covalent linker (i.e.
  • heteroaromatic ring examples include, but are not limited to:
  • heteroaromatic rings with one to four nitrogen atoms but no further heteroatoms, e.g. pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphtyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4H-carbazolyl, carbazolyl, ⁇ -carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, 7H-pyrazino[2,3-
  • heteroaromatic rings with one to four nitrogen atoms and one or more further heteroatoms e.g. phenarsazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazinyl, phenoxazinyl, 5H-pyrido[2,3-d]oxazinyl, 1 H- pyrazolo[4,3-d]oxazolyl, 4H-imidazo[4,5-d]thiazolyl, selenazolo[5,4- f]benzothiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1 -b]thiazolyl, furo[3,4-c]cinnolinyl, 4H-pyrido[2,3-c]carbazolyl, 4H-[1 ,3]oxathiolo-[5,4- b]pyrrolyl and 4H-1 ,3-d
  • Exemplary compounds of this group include, but are not limited to, 2- pyridinesulfonic acid, 3-pyridinesulfonic acid, 4-pyridinesulfonic acid, 4- quinolinesulfonic acid, and 8-quinolinesulfonic acid.
  • the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 2 wherein Het represents a heteroaromatic ring such as, but not limited to, a pyridinyl ring or a quinolinyl ring, and the sulfonate anion is attached to said heteroaromatic ring through a linker being an aliphatic chain with 1 to 4 carbon atoms, i.e. p is 1 to 4.
  • Suitable examples of the heteroaromatic ring are as listed above.
  • Each of the above-mentioned sub-groups of zwitterionic compounds is useful as a catalyst for use in a process for the preparation of an organic ester by reacting a carboxylic acid or an anhydride with an alcohol.
  • a carboxylic acid or an anhydride is reacting a carboxylic acid or an anhydride with an alcohol.
  • the carboxylic acid or anhydride used in the process for producing esters according to the present invention is not particularly limited. Suitable examples thereof include: monocarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms such as, but not limited to, acetic acid, propionic acid, butyric acid, valeric acid, n-hexanoic (caproic) acid, heptanoic (enanthic) acid, octanoic (caprylic) acid, n-nonanoic (pelargonic) acid, n-decanoic (capric) acid, n-dodecanoic (lauric) acid, n-tetradecanoic (myristic) acid, n-octadecanoic (stearic) acid, acetic anhydride, propionic anhydride, butyric anhydride, valeric anhydride and n-hexanoic (caproic) anhydride;
  • monocarboxylic acids including saturated aliphatic acids having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is directly or indirectly (i.e. via a linking heteroatom such as oxygen) substituted with an aromatic ring such as, but not limited to, phenylacetic acid, phenylpropionic acid, 2-phenylbutyric acid, 3-phenylbutyric acid, 4- phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenyl- heptanoic acid, 8-phenyloctanoic acid, 9-phenylnonanoic acid, 10-phenyl- decanoic acid, 12-phenyldodecanoic acid, 16-phenylhexadecanoic acid, 18-phenyl octadecanoic acid, 1 -naphthylacetic acid, 2-naphthylacetic acid, 3-(1
  • monocarboxylic or dicarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is substituted with a saturated or ethylenically unsaturated cycloaliphatic group such as, but not limited to, cyclohexylacetic acid, 1 ,1 -cyclohexanediacetic acid, 4-cyclohexylbutyric acid, 5-cyclohexylvaleric acid, cyclopentylacetic acid, 1 ,1 - cyclopentanediacetic acid, 3-cyclopentylpropionic acid, 2-cyclopentene-1 - acetic acid, 2-ethylhexanoic acid, cyclohexene-1 ,2-dicarboxylic (tetrahydrophthalic) anhydride;
  • ethylenically unsaturated fatty acids or anhydrides having from 8 to 24 carbon atoms such as, but not limited to, oleic acid, 2-octenoic acid and nervonic acid;
  • dicarboxylic saturated aliphatic acids or anhydrides having from 2 to 12 carbon atoms such as, but not limited to, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, and dodecanedioic acid;
  • dicarboxylic ethylenically unsaturated acids or anhydrides having from 4 to 12 carbon atoms such as, but not limited to, fumaric acid, maleic acid, trans-3-hexenedioic (dihydromuconic) acid, and 2-dodecenedioic (trans- traumatic) acid;
  • dicarboxylic aromatic acids or anhydrides such as, but not limited to, terephthalic acid, isophthalic acid, and diphenyl ether-4,4' -dicarboxylic acid;
  • - tricarboxylic acids or anhydrides such as, but not limited to, butane-1 ,2,4- tricarboxylic acid, cyclohexane-1 ,2,3-tricarboxylic acid, cyclohexane-1 ,3,5- tricarboxylic acid, benzene-1 ,2,4-tricarboxylic acid, and naphthalene-1 ,2,4- tricarboxylic acid;
  • - tetracarboxylic acids or anhydrides such as, but not limited to, butane- 1 ,2,3,4-tetracarboxylic acid, cyclobutane-1 ,2,3,4-tetracarboxylic acid, benzene-1 , 2,4, 5-tetracarboxylic acid, 3,3',4,4'-benzophenone tetracarboxylic acid, and 3,3',4,4'-diphenyl ether tetracarboxylic acid;
  • cycloaliphatic saturated and ethylenically unsaturated monocarboxylic or dicarboxylic acids or anhydrides e.g. cyclohexanecarboxylic acid, cyclopentane-carboxylic acid, 1 ,2-cyclopentanedicarboxylic acid and cyclohexene-carboxylic acid;
  • acetylenically unsaturated acids having from 3 to 12 carbon atoms, e.g. propiolic acid, 2-butynoic acid, 4-pentynoic acid or 2-octynoic acid;
  • monocarboxylic aromatic acids or anhydrides e.g. benzoic acid, 4- pentylbenzoic acid;
  • carboxylic acids may have, on the aliphatic chain or the aromatic chain thereof, one or more functional substituents not interfering with the esterification reaction, e.g. functional substituents independently selected from the group consisting of Ci -4 alkyl, Ci -4 alkoxy, nitro, cyano, halogen, fluoro-Ci -4 alkyl and fluoro-Ci -4 alkoxy.
  • functional substituents independently selected from the group consisting of Ci -4 alkyl, Ci -4 alkoxy, nitro, cyano, halogen, fluoro-Ci -4 alkyl and fluoro-Ci -4 alkoxy.
  • An exemplary group of such functional carboxylic acids comprises substituted phenylacetic acids such as, but not limited to, 4- bromophenylacetic acid, 3-bromophenylacetic acid, 2-bromophenylacetic acid, 4-chlorophenylacetic acid, 3-chlorophenylacetic acid, 2-chlorophenylacetic acid, 4-fluorophenylacetic acid, 3-fluorophenylacetic acid, 2-fluorophenylacetic acid, 4-nitrophenylacetic acid, 3-nitrophenylacetic acid, 2-nitrophenylacetic acid, 2,4-dichlorophenylacetic acid, 2,6-dichloro-phenylacetic acid, 3,4- dichlorophenylacetic acid, 4-methoxyphenylacetic acid, 3- methoxyphenylacetic acid, 2-methoxyphenylacetic acid, 4-methylphenyl-acetic acid (p-tolylacetic acid), 3-methylphenylacetic acid (m-tolylacetic acid), 2- methylphenylacetic acid (
  • Another exemplary group of such functional carboxylic acids comprises substituted phenylpropionic acids such as, but not limited to, 3-(2-iodophenyl)propionic acid, 3-(2-bromophenyl)propionic acid, 3- (2-chlorophenyl)propionic acid, 3-(2-fluorophenyl)propionic acid, 3-(3- iodophenyl)propionic acid, 3-(3-bromophenyl)propionic acid, 3-(3- chlorophenyl)propionic acid, 3-(3-fluorophenyl)propionic acid, 3-(4- iodophenyl)propionic acid, 3-(4-bromophenyl)propionic acid, 3-(4- chlorophenyl)propionic acid, 3-(4-fluorophenyl)propionic acid, 2-(4- chlorophenyl)propionic acid, 2-(2-chlorophenyl)propionic acid, 3-(4
  • Another exemplary group of such functional carboxylic acids comprises substituted benzoic acids such as, but not limited to, 2-chlorobenzoic acid, 3- chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 3- bromobenzoic acid, 4-bromobenzoic acid, 2-fluorobenzoic acid, 3- fluorobenzoic acid, 4-fluorobenzoic acid, 4-aminobenzoic acid, 4-amino-5- chloro-2-methoxybenzoic acid, 4-amino-2-chlorobenzoic acid or 4-amino-3- nitrobenzoic acid.
  • substituted benzoic acids such as, but not limited to, 2-chlorobenzoic acid, 3- chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 3- bromobenzoic acid, 4-bromobenzoic acid, 2-fluorobenzoic acid, 3- fluorobenzoic acid, 4-fluorobenzoic acid, 4-amino
  • the alcohol used in the process for producing esters according to the present invention is not particularly limited. Suitable examples thereof include: - saturated aliphatic monohydric alcohols such as, but not limited to, methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, undecanol, dodecanol, nonanol, 2-ethylhexanol, 2-heptylheptanol and stearyl alcohol;
  • alicyclic monohydric alcohols such as, but not limited to, cyclohexanol and cyclododecanol;
  • aromatic monohydric alcohols such as, but not limited to, benzyl alcohol
  • polyhydric alcohols such as, but not limited to, ethylene glycol, propylene glycol, neopentyl glycol, trimethylol propane, trimethylol ethane, pentaerythritol, dipentaerythritol, sorbitol, and polyvinyl alcohol;
  • alicyclic dihydric alcohols such as, but not limited to, cyclohexane-1 ,2-diol and cyclopentane-1 ,2-diol;
  • aliphatic monohydric alcohols such as, but not limited to, allyl alcohol. These alcohols may be primary alcohols or secondary alcohols.
  • One or more functional groups not interfering with the esterification reaction e.g. functional groups independently selected from the group consisting of Ci -4 alkoxy, nitro, cyano, halogen, fluoro-Ci -4 alkyl and fluoro-Ci -4 alkoxy, may be present on the aliphatic chain of the alcohol.
  • a functional group containing a nitrogen atom such as an amino group, may be capable of interfering with the esterification reaction by deprotonating the catalyst of the invention, and consequently should be avoided.
  • the reaction proceeds when either one of the carboxylic acid or the alcohol is used in a molar excess amount
  • the reaction also suitably proceeds when equimolar amounts of the carboxylic acid and the alcohol are used. It is accordingly an object of the present invention to provide a process for the preparation of an organic ester by reacting a carboxylic acid or anhydride with an alcohol in the presence of a zwitterionic catalyst as defined herein and wherein equimolar amounts of the carboxylic acid and the alcohol are used.
  • the process for the preparation of organic esters as provided herein may proceed in the absence of a reaction solvent.
  • the process for producing esters according to the present invention will proceed in the presence of at least one solvent.
  • the reaction solvent optionally used in the process of this invention is not particularly limited as long as it is inactive in the esterification reaction.
  • the reaction solvent may be a non-polar solvent or a polar solvent; it can either form a homogeneous or biphasic mixture at the start or end of the reaction at any given temperature. If it forms at the end of the reaction a biphasic mixture, it can act as a water and/or catalyst removal in particular when a polar ionic liquid is used with physicochemical properties suited for this purpose.
  • reaction solvent examples include:
  • aliphatic and cycloaliphatic saturated hydrocarbons such as, but not limited to, hexane, heptane, cyclohexane, methylcyclohexane, octane, and mixtures thereof;
  • - halogenated alkanes such as, but not limited to, methylene chloride, chloroform, carbon tetrachloride, and ethylene chloride
  • - aromatic hydrocarbons such as, but not limited to, benzene, toluene, xylene, mesitylene, and pentamethylbenzene
  • halogenated aromatic hydrocarbons such as, but not limited to, chlorobenzene and bromobenzene
  • - ethers such as, but not limited to, diethyl ether, anisole, THF, 2-MeTHF, 1 ,4-dioxane, (EtO) 2 CH 2 , and MBTE; and
  • Ionic Liquids such as but not limited to EMIM CI (1 -Ethyl-3- methylimidazolium chloride), BMIM CI (1 -Butyl-3-methylimidazolium chloride), EMIM MeSO 3 (1 -Ethyl-3-methyl imidazolium methanesulfonate), EMIM EtOSO 3 (1 -Ethyl-3-methyl imidazolium ethylsulfate) EMIM DEP (1 -Ethyl-3- methyl imidazolium diethylphosphate), EMIM DCA (1 -Ethyl-3-methyl imidazolium dicyanamide) EMIM OAc (1 -Ethyl-3-methyl imidazolium acetate) MTEOA MeOSO 3 (Tris-(2-hydroxyethyl)-methylammonium methylsulfate), EMIM BF 4 (1 -Ethyl-3-methyl imidazolium tetraflu
  • the amount of the zwitterionic compound used as a catalyst in the process for producing esters according to the present invention is appropriately set depending on the esterification reaction system (i.e. types of carboxylic acid and alcohol used as reactants, type of reaction solvent, etc.), using general knowledge of the person skilled in the art.
  • the zwiterionic compound may be used in an amount ranging from about 0.01 % to about 20 mole %, in particular from about 0.1 % to about 10 mole %, more particularly from about 0.2% to about 5 mole % with respect to the amount of carboxylic acid or anhydride or the amount of alcohol, whichever is lower.
  • the reaction temperature and the reaction time are appropriately set depending on the esterification reaction system (i.e. the type of carboxylic acid or anhydride and the type of alcohol used as reactants, type of reaction solvent, etc.), using general knowledge of the person skilled in the art.
  • the reaction temperature may be ranging from about 10 °C to about 180 °C, in particular from about 20 °C to about 100 °C.
  • the esterification reaction may proceed at room temperature in the absence of a solvent.
  • the reaction is carried out for a period of time after which a predetermined molar amount of the desired ester has been formed, or until either the carboxylic acid or the alcohol has substantially disappeared.
  • the reaction time usually ranges from about 0.5 hour to about 72 hours.
  • water produced by the esterification reaction may be actively removed from the reaction system, either continuously or discontinuously, using general knowledge of the person skilled in the art.
  • the process for producing organic esters as provided herein may be allowed to proceed either with or without removing produced water from the reaction mixture.
  • the esterification catalyst may be separated from the reaction mixture after esterification has been substantially completed and may be reused a significant number of times without losing activity or selectivity.
  • the process for the preparation of an organic ester may be performed in the presence of a solvent that phase separates after the reaction and can contain water and/or the catalyst in one of said phase.
  • Exemplary solvents to be used in this embodiment include ionic liquids such as EMIM CI (1 -Ethyl-3-methylimidazolium chloride), BMIM CI (1 -Butyl-3- methylimidazolium chloride), EMIM MeSO 3 (1 -Ethyl-3-methyl imidazolium methanesulfonate), EMIM EtOSO3 (1 -Ethyl-3-methyl imidazolium ethylsulfate) EMIM DEP (1 -Ethyl-3-methyl imidazolium diethylphosphate), EMIM DCA (1 - Ethyl-3-methyl imidazolium dicyanamide) EMIM OAc (1 -Ethyl-3-methyl imidazolium acetate) MTEOA MeOSO 3 (Tris-(2-hydroxyethyl)- methylammonium methylsulfate), EMIM BF (1 -Ethyl-3-methyl imidazolium
  • the present invention relates to certain methods for producing the zwitterionic compounds that are used as esterification catalysts. Such methods are illustrated in the single appended figure 1
  • Both methods shown in figure 1 include the combination of a sulfonation step and a coupling step, however in different order.
  • a first method (shown on the right side of the figure) involves the sulfonation of a starting material bearing an ammonium cation, followed by the coupling of the resulting intermediate with a Rrcontaining reactant RiX wherein X may be selected from the group consisting of iodo, bromo, chloro, triflate, B(OH) 2 and BF 3 K.
  • the present invention relates to a method for producing /V-aryl-sulfanilic acids, /V-aryl-orthanilic acids, /V-aryl-metanilic acids and 5-(/V-arylamino)-o-toluenesulfonic acids wherein an aryl iodide is reacted, in the presence of a base such as an alkaline alkoxide and a catalytic amount of a transition metal complex of an organophosphorous ligand, with sulfanilic acid, orthanilic acid, metanilic acid or 5-amino-o-toluenesulfonic acid, respectively.
  • a base such as an alkaline alkoxide and a catalytic amount of a transition metal complex of an organophosphorous ligand
  • the method of this particular embodiment may be performed in an organic solvent such as an ether, e.g. a cyclic ether.
  • the method of this particular embodiment may be performed at a temperature ranging from about 40°C to about 140°C for a period of time ranging from about 4 to 78 hours.
  • the transition metal complex used in the method of this particular embodiment may be a complex of copper, nickel, iron or palladium.
  • the organophosphorous ligand used in the method of this particular embodiment may be a -ligand such as, but not limited to, ( ⁇ )-2,2'-bis(diphenylphosphino)-1 ,1 '- binaphthyl (racemic) (BINAP).
  • Bases that may be used in the method of this particular embodiment include, but are not limited to, sodium terf-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide and potassium hydroxide.
  • Aryl iodides that may be used in the method of this particular embodiment include, but are not limited to, phenyl iodide, naphthyl iodide, 2-iodotoluene, 3-iodotoluene, 4-iodotoluene, iodomesitylene, 1 -iodo- 2,3-dimethylbenzene, 1 ,4-dimethyl-2-iodobenzene, 2-iodo-m-xylene, 4-iodo- m-xylene, 5-iodo-m-xylene and 4-iodo-o-xylene.
  • the present invention relates to a method for producing /V-substituted sulfanilic acids, comprising reacting a N- substituted aniline derivative or ⁇ /,/V-disubstituted aniline derivative with a non- acidic sulfonating agent.
  • the method of this particular embodiment may be performed in the presence or absence of an organic solvent.
  • the method of this particular embodiment may be performed at a temperature ranging from about 40°C to about 180°C for a period of time ranging from about 1 hour to about 48 hours.
  • the non-acidic sulfonating agent may be bis(trimethylsilyl) sulfate, sulfuric acid or chlorosulfonic acid.
  • Table 1 shows the sulfonated aniline derivative yield (expressed as %) obtained after a certain period of time (expressed in hours).
  • Benzoic acid (648 mg, 5.06 mmol), cyclohexanol (507 mg, 5.07 mmol), toluene (5 ml), dodecane (1 14 ⁇ , 0.5 mmol) and 4- (phenylamino)benzenesulfonic acid (40 mg, 0.15 mmol) were added in a round round-bottom flask with a reflux condenser.
  • the reaction mixture was stirred at 90°C in an oil bath for 24 hours.
  • 3-phenyl propionic acid (760 mg, 5.06 mmol) was added to ethanol (1 .2 ml, 21 mmol).
  • the reaction mixture was heated at 80°C.
  • the catalyst 25 mg was added to the solution.
  • the reaction mixture was heated at 80°C for several hours.
  • Table 3 shows the yield of 3-phenylpropanoic ethanoate (expressed as %) obtained after a certain period of time (expressed in hours). Entry 1 is given for comparative purpose.
  • Table 5 shows the yield of ester (expressed as %) obtained after a certain period of time (expressed in hours).
  • a 25-mL, round-bottomed flask equipped with a magnetic stirring bar and a septum was dried and allowed to cool to room temperature under a nitrogen balloon.
  • the flask was charged with sodium terf-butoxide (2.5 molar equiv., 650 mg) (3), dioxane (8 mL) (6), water (2 mL) (7), ortho-anilinic acid (1 .3 molar equiv.) (2), an aryl iodide (1 molar equiv.) (1) and ( ⁇ )-BINAP (0.014 molar equiv., 23 mg).
  • the septum was placed on the flask, and the flask was purged with nitrogen for about 20 minutes.
  • a 25-mL, round-bottomed flask equipped with a magnetic stirring bar and a rubber septum was dried and allowed to cool to room temperature under a nitrogen balloon.
  • the septum was removed and the flask was charged with sodium terf-butoxide (2.3 molar equiv., 1 .1 g), toluene (8 ml_), sulfanilic acid (1 .2 molar equiv.), an aryl iodide (1 molar equiv.) and ( ⁇ )-BINAP (0.014 molar equiv., 23 mg).
  • the septum was again placed on the flask, and the flask was purged with nitrogen for about 20 minutes.
  • the flask was charged with bis(dibenzylideneacetone)palladium(0) (0.007 molar equiv., 1 1 mg).
  • the resulting dark red mixture was placed in an oil bath that was heated to 80°C.
  • the reaction was monitored by LC/MS, using Agilent 1 100 fitted with a column Agilent Zorbax Eclipse C8 (analytical, 4.6 x 150 mm, 5 ⁇ ).

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Abstract

The present invention relates to zwitterionic compounds which are useful as catalysts for the preparation of organic esters. In particular, the present invention relates to sulfonic acid compounds, such as arenesulfonic acid compounds, including a nitrogen atom in their structure and zwitterionic forms thereof, being useful as catalysts for esterification reactions. The present invention also relates to processes for making such compounds. The present invention also relates to esterification processes catalysed by such zwitterionic compounds. In particular, the present invention relates to processes for the preparation of organic esters wherein a zwitterionic catalyst may be recycled and re-used a significant number of times without losing its catalytic activity and/or selectivity.

Description

ZWITTERIONIC COMPOUNDS USEFUL AS CATALYSTS FOR ESTERIFICATION REACTIONS AND PROCESSES FOR THEIR PRODUCTION FIELD OF THE INVENTION
The present invention relates to zwitterionic compounds which are useful as catalysts for the preparation of organic esters. In particular, the present invention relates to sulfonic acid compounds, such as arenesulfonic acid compounds, including a nitrogen atom in their structure and zwitterionic forms thereof, being useful as catalysts for esterification reactions. The present invention also relates to processes for making such compounds. The present invention also relates to esterification processes catalysed by such zwitterionic compounds. In particular, the present invention relates to processes for the preparation of organic esters wherein a zwitterionic catalyst may be recycled and re-used a significant number of times without losing its catalytic activity and/or selectivity.
BACKGROUND OF THE INVENTION
A significant number of sulfonic compounds, such as arenesulfonic compounds, including a nitrogen atom in their structure are already known in the art. This class of aromatic compounds also includes a few sulfanilic acids, i.e. compounds bearing both an amino group and a sulfonic acid group directly attached to the aromatic (phenyl) ring. However, as far as we know, only very limited use has been made of sulfanilic acids in the catalysis of organic reactions such as esterification reactions. Because of their two functional groups, sulfanilic acids are amphoteric. In the solid state, their sulfonic acid group is able to protonate the amine function, thus forming a zwitterion. The ammonium sulfonate form may be favored because an ammonium ion is usually much less acidic than a sulfonic acid. The structure of sulfanilic acids in a solution, e.g. an aqueous solution, depends on the pH.
Esters are useful in a wide variety of industrial applications, such as plasticizers, lubricants, lubricant additives, lacquer bases, perfumes, cosmetics, foods, coatings, adhesives, resins, fragrances, solvents, extractants, etc.
Esterification is one of the most fundamental and important reactions in organic synthesis. Several synthetic routes exist to make esters, but most of them are not suitable to meet the stringent specifications which are being applied in the chemical industry. The most acceptable method of making an ester, is to react an acid with an alcohol in the presence of a catalyst, as shown in the scheme below. This reaction is a well known equilibrium-limited reaction involving reacting a mono-, di- or polycarboxylic acid (or, in suitable cases, a carboxylic acid anhydride) with an alcohol or phenol component. Such an alcohol or henol component can be mono, di- or polyhydric.
Figure imgf000003_0001
Rl 5 R2 = (Substituted) alkyl or aryl
In order to achieve complete esterification, either one of the reactants (alcohol or acids) is used in large access or, one of the resulting products (water or ester) is removed from the equilibrium by distillation. The choice of method to achieve complete esterification depends on the boiling points of the alcohol, the acid, and the ester. Basically, the following three possibilities exist: a. The boiling point of the ester is lower than that of water: in this case the ester can be distilled off together with the alcohol.
b. Ester and water can be distilled off together, usually as an azeotropic mixture. On condensation, the mixture separates into an ester and a water phase. To achieve complete evaporation of the ester, water or steam are often added to the reaction mixture.
c. The boiling point of the ester is higher than that of water. In this case, the water is distilled off, frequently as an azeotrope with the alcohol. Alternatively, an entrainer (co-solvent) can be used. The need to remove one of the components or to use an entrainer which often forms binary or ternary azeotropes with other reaction components often complicates the technical set-up and purification.
In an alternative classification based on the type of catalyst and reaction conditions, the processes of making esters from acids and alcohols can also be classified into the following two main categories:
(a) Homogeneous liquid phase esterification reaction using an acid catalyst: this type of process uses Bransted acids, such as sulfuric acid, phosphoric acid, methylsulfonic acid, p-toluenesulfonic acid, or a Lewis acid catalyst, such as titanium, tin, hafnium or zirconium compounds, as a catalyst.
(b) Heterogeneous liquid phase esterification reaction using a solid Br0nsted or Lewis acid catalyst: this type of process typically uses inorganic salts, cationic ionic exchange resin and solid acids catalysts (such as clays or zeolites).
One of the problems associated with homogeneous esterification reaction processes using a Bransted acid catalyst is that strong acids cause corrosion in the reactor. These Br0nsted acid catalysts are also discharged along with the reaction products, thus causing serious waste disposal and pollution problems. The drawbacks of using the traditional mineral acid as catalyst include:
(i) catalyst cannot be reused,
(ii) disposal of acid is not environmentally safe and/or economical,
(iii) low selectivity is frequently observed,
(iv) corrosion of the reaction vessel and reactors,
(v) uneasy to handle, and
(vi) high inventory of the catalyst.
Additional to the drawbacks of Br0nsted acids, the use of Lewis acids generates waste streams containing toxic heavy metals with high associated disposal costs and negative impact on the environment. In specific cases, high temperatures are needed to improve the reaction.
The heterogeneous esterification reaction, which typically utilizes a cationic ionic exchange resin as catalyst, ameliorates the corrosion and waste disposal problems experienced with the homogeneous processes, and results in simplified separation procedure required between the reaction product and catalysts. However, these reactions show slower and more complex kinetics. In addition, cationic ion-exchange resins typically exhibit relatively poor heat- resistance, and they often lose substantial activity after being subject to heat. Once the catalytic activity of the cationic ion-exchange resins is reduced, it is difficult to be regenerated.
In the gas phase esterification reaction, reaction conditions are maintained so that all reactants and products are in the gas phase. Typically, inorganic materials are used as catalysts which typically exhibit excellent heat resistance and can be easily separated from the reaction products. However, the gas phase reaction necessitates a relatively large reaction vessel, resulting in large capital investment costs. Furthermore, if the gas phase esterification reaction is used to produce unsaturated carboxylic esters, the high reaction temperature often causes undesired by-products like polymers or oligomers to be produced. In certain instances, the high reaction temperature has even caused the alcohol molecule to be dehydrated to become an ethers or alkene. These side-reactions tend to cause the reaction catalysts to lose their activity and result in operational difficulties.
One approach to circumvent the above-mentioned problems of the current esterification processes is the use of Bransted acid ionic liquids as both a catalyst, a solvent and a dehydrating medium. Water formed during the reaction is taken up by the ionic liquid and the ester product forms a separate phase. In addition, the use of ionic liquids, which are practically non-volatile, obviates the need for volatile organic solvents. These Br0nsted acid ionic liquids are conveniently made by adding a strong acid (HA) to a weak base (B) according to the following scheme:
B + HA ^ — BH+ + A"
The weak base can be an alkylsulfonate, an imidazole, a trialkylamine, a pyridine or an aniline.
Shortcomings to this approach is the fact that ionic liquids often need to be used in large access (50 mole %). We also observed that the separation step is often hampered by the fact that the ionic liquid is in equilibrium with the free acid and base due to the very high Madelung stabilization energy of the zwitterionic compound as a polymeric solid and together with the high solubility of the free acid in the organic medium. This equilibrium often causes unwanted leaching of one of the catalyst components in the product phase which results in an undesired contamination and makes the recycling of the catalyst impossible. In order to overcome the latter problem, the weak base and strong acid can be connected by covalent bonding which results into a zwitterionic compound. An example is sulfamic acid, which is hydrolytically unstable, thus making it unsuitable for industrial esterifications. Another class of zwitterionic compounds are sulfanilic acids mentioned herein-above. These have scarcely been used in the preparation of esters. It is known in the art to use p-aminobenzenesulfonic acid (i.e. p-sulfanilic acid) as a catalyst for the esterification reactions of :
- stearic acid with glycol,
- acetic acid with isoamyl alcohol,
- benzoic acid or adipic acid with n-hexyl alcohol, and
- phthalic anhydride with an alcohol having from 7 to 9 carbon atoms.
To summarize, in order to efficiently use a catalyst for the promotion of an esterification reaction, a high number of capabilities are usually required from a catalyst candidate:
- the catalyst should exhibit high activity, i.e. actively and efficiently promote the esterification reaction within a limited period of time,
- the catalyst should exhibit high selectivity, i.e. avoid the possibility for undesirable side reactions, such as ether formation and dehydration.
- the catalyst should exhibit sufficient stability under the prevailing operating conditions to be capable of recycling and re-using in the esterification reaction without losing its activity and selectivity, and
The catalyst should also be inexpensive to produce, although an extra production cost may be admissible when a candidate is able to be recycled and re-used significantly more than another catalyst. If possible, the suitable candidate should also exhibit sufficient versatility, i.e. be active and selective in the highest possible number of esterification reactions or, otherwise said, its activity and selectivity should depend as little as possible upon the types of acid (or anhydride) and alcohol used in the esterification reactions, and upon the operating conditions used (e.g. temperature, pressure, presence of optional co-catalysts, etc.). All these requirements still to date constitute a stringent need in the field of organic chemistry.
OBJECT AND ADVANTAGES OF THE PRESENT INVENTION
The object of the present invention is to avoid the drawbacks of prior art esterification catalysts and processes by providing a new class of esterification catalysts being useful in the performance of processes for the preparation of organic esters.
An advantage of the present invention is to provide catalysts and processes for the preparation of organic esters which are environmentally friendly.
Another advantage of the present invention is to provide processes for the preparation of organic esters that easily allow catalyst removal.
Another advantage of the present invention is to provide processes for the preparation of an ester that allow catalyst multiple reuse.
Another advantage of the present invention is to provide esterification processes that are economical and efficient.
Another advantage of the present invention is to provide processes for producing esters wherein esterification proceeds rapidly without the formation of by-products originating from the starting alcohols such as, but not limited to, alkenes or ethers.
Another advantage of the present invention is to provide novel esterification catalysts having high catalytic activity while effectively avoiding the formation of by-products originating from alcohols.
SUMMARY OF THE INVENTION
According to one embodiment, the present invention relates to a process for the preparation of an organic ester, comprising reacting a carboxylic acid or anhydride with an alcohol in the presence of a zwitterionic catalyst, in particular a zwitterionic catalysts as represented by formula 1 below, preferably at a temperature from about 10°C to about 180°C for a time period ranging from about 0.5 to 72 hours, and separating the ester formed from the reaction mixture, provided that said zwitterionic catalyst is not m-sulfanilic acid or p-sulfanilic acid when used as a catalyst for the esterification of :
- stearic acid with glycol,
- citric acid with a fatty alcohol,
- acetic acid with isoamyl alcohol,
- benzoic acid or adipic acid with n-hexyl alcohol, or
- phthalic anhydride with an alcohol having from 7 to 9 carbon atoms.
According to another embodiment, the present invention relates to a novel esterification catalyst being a zwitterionic compound having a ammonium group covalently linked to a sulfonate group optionally by means of a linker provided that said zwitterionic compound is not m-sulfanilic acid or p-sulfanilic acid, especially when used as a catalyst for the esterification of :
- stearic acid with glycol,
- citric acid with a fatty alcohol,
- acetic acid with isoamyl alcohol,
- benzoic acid or adipic acid with n-hexyl alcohol, or
- phthalic anhydride with an alcohol having from 7 to 10 (branched) carbon atoms. When no linker is present in the zwitterionic compound (i.e. the ammonium group is directly linked to the sulfonate group), the ammonium group of the zwitterionic compound of this other embodiment of the present invention should not be a primary ammonium group but may be a secondary ammonium group, a tertiary ammonium group or a quaternary ammonium group.
According to another embodiment, the present invention relates to a process for producing an organic ester including the step of allowing a carboxylic acid or anhydride to react with an alcohol, wherein an zwitterionic compound is used as catalyst, as used herein also referred to as a zwitterionic catalyst, said zwitterionic compound (or zwitterionic catalyst) containing an ammonium cation and a sulfonate anion and including a structural moiety represented by the formula 1 :
Figure imgf000009_0001
1
wherein:
- Ri and R'i are independently selected from the group consisting of hydrogen, Ci-4 alkyl, and aryl optionally substituted with one, two or more Ci-4 alkyl substituents;
- R4 is independently hydrogen or CMO alkyl;
- p is 0 to 8;
- L represents a direct bond, a bivalent radical of the formula
Figure imgf000009_0002
R2 wherein - R2 is independently hydrogen or CMO alkyl;
- m is 0 to 4; n is 0 or 1 ;
- Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci-4 alkyl, aryl, benzyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, aryloxy, Ci-4 alkylthio, arylthio and fluoro-Ci-4 alkoxy; or
- L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring;
provided that;
when the sum of m, n and p is 0, then at least one of Ri and R'i does not represent hydrogen;
- when L represents the bivalent radical of formula (a1 ), and Ar represents napthyl, then the ammonium cation group and the sulfonate anion group are at positions 1 and 8 of the naphtyl residue;
- when L represents the bivalent radical of formula (a1 ), m is 0, n is 1 , Ar represents phenyl, at least one of Ri and R'i does not represent hydrogen, and p is 0, then the ammonium cation group and the sulfonate anion group are present in ortho position of one another, and - provided that said zwitterionic compound is not m-sulfanilic acid or p- sulfanilic acid.
According to a particular embodiment the zwitterionic compound used in the aforementioned compound comprises an aromatic ring between the ammonium cation group and the sulfonate anion group, and corresponds to said compounds of formula 1 , wherein
- L represents a bivalent radical of the formula
Figure imgf000010_0001
wherein m is 0 and n is 1 ;
Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci-4 alkyl, aryl, benzyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, aryloxy, Ci-4 alkylthio, arylthio and fluoro-Ci-4 alkoxy; in particular Ar represents phenyl or naphtyl optionally substituted with Ci-4 alkyl;
provided that;
- when L represents the bivalent radical of formula (a1 ), and Ar represents napthyl, then the ammonium cation group and the sulfonate anion group are at positions 1 and 8 of the naphtyl residue;
- when L represents the bivalent radical of formula (a1 ), m is 0, n is 1 , Ar represents phenyl, at least one of Ri and R'i does not represent hydrogen, and p is 0, then the ammonium cation group and the sulfonate anion group are present in ortho position of one another, and
- provided that said zwitterionic compound is not m-sulfanilic acid or p- sulfanilic acid.
According to a further particular embodiment the zwitterionic compound used in the aforementioned process is defined as in any one of the foregoing embodiments, but with the proviso that said zwitterionic compound is not o- sulfanilic acid, m-sulfanilic acid or p-sulfanilic acid. According to a further particular embodiment the zwitterionic compound used in the aforementioned process comprises a heteroaromatic ring, i.e. consists of those compounds of formula 1 , wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; structurally represented by formula 2
Figure imgf000011_0001
wherein:
- Het designates a heteroaromatic ring structure containing one to four nitrogen atoms and a total of 5 to 17 ring atoms; in particular containing one nitrogen atom; more in particular Het designates a heterocyclic iminium cation; even more in particular Het designates a pyridinium ring;
- each R5 is independently selected from the group consisting of hydrogen, C-1 -4 alkyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, Ci-4 alkylthio and fluoro-Ci-4 alkoxy; in particular R5 is hydrogen;
- each R is independently selected from the group consisting of hydrogen and C-1-10 alkyl; in particular R4 is hydrogen, and
- p is 0 to 8; in particular p is 0 to 4. In a further aspect the present invention provides novel esterification catalysts being a zwitterionic compound having an ammonium cation group covalently linked to a sulfonate anion group optionally by means of a linker; said zwitterionic catalysts generally represented by formula 1 wherein;
Figure imgf000011_0002
1 wherein:
- Ri and R'i are independently selected from the group consisting of hydrogen, Ci-4 alkyl, and aryl optionally substituted with one, two or more C1-4 alkyl substituents;
- R is independently hydrogen or C1-10 alkyl;
- p is 0 to 8;
- L represents a direct bond, a bivalent radical of the formula
Figure imgf000012_0001
R2 wherein - R2 is independently hydrogen or CMO alkyl;
- m is 0 to 4; n is 0 or 1 ;
- Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci-4 alkyl, aryl, benzyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, aryloxy, Ci-4 alkylthio, arylthio and fluoro-Ci-4 alkoxy; or
- L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring;
provided that;
when the sum of m, n and p is 0, then at least one of Ri and R'i does not represent hydrogen;
- when the sum of m and p is 0, n is 1 , and Ar represents phenyl, then at least one of Ri and R'i does not represent hydrogen, and then the ammonium cation group and the sulfonate anion group are present in ortho position of one another; and
- when L represents the bivalent radical of formula (a1 ), and Ar represents napthyl, then the ammonium cation group and the sulfonate anion group are at positions 1 and 8 of the naphtyl residue.
Evidently, is also an object of the present invention to provide the use of the aforementioned zwitterionic catalysts in the esterification process as provided herein. BRIEF DESCRIPTION OF THE DRAWING
The single figure schematically shows synthetic routes for producing zwitterionic compounds used as esterification catalysts according to the present invention.
Ri
H-N-L—
Figure imgf000013_0001
L— [CH2]p-S03-
R^1 R
I Coupling^ /sulfonation
with F^X
H-N-L— [CH2]P-Y
R^" R
wherein Ri , Ri', R , p, and L are defined as for the compounds of formula 1 hereinbefore; and wherein Y represents H, CI, Br, I, paratoluenesulfonate (OTs) or trifluoromethanesulfonate (OTf); and wherein X represents I, Br, CI, OTf or BR2 with R2 as defined for the compounds of formula 1 hereinbefore
DEFINITIONS
As used herein with respect to a substituting group, and unless otherwise stated, the term " Ci-4alkyl " refers to a straight or branched chain saturated acyclic hydrocarbon monovalent group having from 1 to 4 carbon atoms such as, for example, methyl, ethyl, propyl, n-butyl, 1 -methylethyl (isopropyl), 2-methylpropyl (isobutyl), and 1 ,1 -dimethylethyl (terf-butyl). Similarly, the term " CMO alkyl " refers to a substituting group having from 1 to 10 carbon atoms such as, for example, n-pentyl, isoamyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl.
As used herein with respect to a group or moiety, and unless otherwise stated, the terms " aryl " and " aromatic ring " refer to any mono- or polycyclic aromatic monovalent hydrocarbon group having from 6 up to 30 carbon atoms such as, but not limited to, phenyl, naphthyl, anthracenyl, phenanthracyl, fluoranthenyl, chrysenyl, pyrenyl, biphenylyl, terphenyl, picenyl, indenyl, biphenyl, indacenyl, benzocyclobutenyl, benzocyclooctenyl and the like, including fused benzo-C4-s cycloalkyl radicals such as, for instance, indanyl, tetrahydronaphtyl, fluorenyl and the like, all of the said groups being optionally substituted with one or more substituents independently selected from the group consisting of halogen, Ci-4alkyl, nitro, difluoromethoxy, trifluoro- methoxy, trifluoromethyl and Ci-4alkoxy (all of them being such as herein defined, including sub-groups thereof) such as, but not limited to, fluorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 2-fluorophenyl, 3-chlorophenyl, 3,5-dichlorophenyl, trifluoromethylphenyl, trifluoromethoxy- phenyl, difluoromethoxyphenyl and 3,4-dimethoxyphenyl; when the substituent is Ci-4alkyl, the resulting substituted aryl may also be designated as Ci-4 alkylaryl such as, but not limited to, o-toluyl, m-toluyl, p-toluyl, mesityl and the like.
As used herein with respect to a substituting group, and unless otherwise stated, the term " Ci-4 alkoxy " refers to substituent wherein a carbon atom of a Ci-4 alkyl is attached to an oxygen atom through a single bond such as, but not limited to, methoxy, ethoxy, propoxy, n-butoxy, isopropoxy, sec-butoxy, terf-butoxy and the like.
As used herein with respect to a substituting group, and unless otherwise stated, the term " Ci-4 alkylthio " refers to substituent wherein a carbon atom of a Ci-4 alkyl is attached to an sulfur atom through a single bond such as, but not limited to, methylthio.
As used herein with respect to a substituting atom, and unless otherwise stated, the term halogen means any atom selected from the group consisting of fluoro, chloro, bromo and iodo.
As used herein with respect to a substituting group, and unless otherwise stated, the terms " fluoro Ci-4alkyl " and " fluoro Ci-4alkoxy " respectively refer to a Ci-4alkyl or Ci-4alkoxy group (such as above defined, including sub-species thereof) in which one or more hydrogen atoms are independently replaced by a corresponding number of fluoro atoms such as, but not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, and the like. As used herein with respect to a group or moiety, and unless otherwise stated, the term " heteroaromatic ring " refers to any mono- or polycyclic aromatic monovalent group having at least one heteroatom such as nitrogen, oxygen, sulfur or selenium; within the scope of the present invention, the preferred heteroaromatic rings include at least one nitrogen atom and optionally one or more further heteroatoms independently selected from the group consisting of nitrogen, oxygen, sulfur or selenium.
DETAILED DESCRIPTION OF THE INVENTION
Compared to the ionic liquid catalysts such as for example described in CN1762974, the present invention differs in that the charged moieties are structurally integrated within one and the same molecule. As such and different from the ionic liquids (salts) typically used in esterification reactions, there is no phase separation of the catalytic components during the reaction. Accordingly, a characterizing feature of the present invention is that the catalytic compound used in the esterification reaction may exist as a zwitterionic form under certain pH conditions, preferably as a zwitterionic compound including both a sulfonate anion and an ammonium or heterocyclic iminium cation. A more particular zwitterionic compound for use in the esterification process of the present invention includes a structural moiety represented by the generic formula 1
According to one embodiment, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein an aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. L represents the bivalent radical (ai ) wherein n is 1 , and wherein no aliphatic chain is present as a linker between the sulfonate anion or the ammonium cation and said aromatic ring, i.e. m and p are each 0. In this situation, the sulfonate anion is either in ortho- , metha- or para-position with respect to the ammonium cation, with the proviso that when in this situation the aromatic ring represents phenyl and the ammonium cation is further substituted with an optionally substituted aryl, then the sulfonate anion is in ortho-position with respect to the ammonium cation. In each of these situations, the zwitterionic compound of the present invention may still include one or more aliphatic chains either attached to the nitrogen atom of the ammonium cation (i.e. R'i in the aforementioned definition of formula 1), or as a substituent (i.e. Optionally substituted aryl' in the aforementioned definition of formula 1 ) of the aromatic ring, or both. Within this embodiment of the present invention, the aromatic ring may be monocyclic, e.g. phenyl, or the aromatic ring may be bicyclic, e.g. naphthyl. In the latter situation, either the sulfonate anion and the ammonium cation may be borne by the same ring (e.g. 2-amino-1 -naphthalenesulfonic acid or 4-amino-1 -naphthalenesulfonic acid) or the sulfonate anion may be borne by one ring and the ammonium cation may be borne by the other ring (e.g. 8-amino-1 -naphthalenesulfonic acid), in a particular embodiment the sulfonate anion is born by one ring and the ammonium cation is borne by the other ring.
According to another embodiment, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein no aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. those compounds of formula 1 wherein L represents a direct bond, but an aliphatic chain with at least one carbon atom, preferably 2 to 8 carbon atoms, is present between the sulfonate anion and the ammonium cation, i.e. p is from 1 to 8. In this situation, the zwitterionic compound of the present invention may still include one or more aromatic rings attached to the nitrogen atom of the ammonium cation (i.e. Ri and/or R'i in the aforementioned definition of formula 1 ).
According to another embodiment, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein no aromatic ring is present between the sulfonate anion and the ammonium cation, i.e. those compounds of formula 1 wherein L represents a direct bond, but further characterized in that the ammonium cation group should not be a primary ammonium group but may be a secondary ammonium group, a tertiary ammonium group or a quaternary ammonium group, i.e. at least one of Ri and/or R'i in the aforementioned definition of formula 1 does not represent hydrogen. According to another embodiment, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein an aromatic ring is present between the sulfonate anion and the ammonium cation, and at least an aliphatic chain with 1 to 4 carbon atoms is present as a linker between the sulfonate anion and said aromatic ring and/or between the ammonium cation and said aromatic ring, i.e. those compounds of formula 1 wherein L represents the bivalent radical (ai) with m is 1 to 4, and wherein p is 1 to 4; alternatively those compounds of formula 1 wherein L represents the bivalent radical (ai) with m is 0 to 4, and wherein p is 1 to 4, in particular p is 1 ; in an even further embodiment those compounds of formula 1 wherein L represents the bivalent radical (ai) with m is 1 to 4, and wherein p is 0 to 4 . According to a more specific feature within these embodiments, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 1 wherein Ar represents a phenyl ring; in particular an optionally substituted phenyl ring. In either of the aforementioned embodiments the sulfonate anion is in particularly in the ortho-position with respect to the ammonium cation, and an aliphatic chain with one carbon atom (i.e. p is 1 ) is present as a linker between the sulfonate anion and said phenyl ring.
According to another embodiment of the present invention the zwitterionic compounds include a heteroaromatic ring, i.e. those compounds of formula 1 wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; such as, but not limited to, a pyridinyl ring or a quinolinyl ring, and the sulfonate anion is directly (i.e. p is 0) or with a covalent linker (i.e. p is 1 to 4) attached to said heteroaromatic ring.
Suitable examples of the heteroaromatic ring include, but are not limited to:
- heteroaromatic rings with one to four nitrogen atoms but no further heteroatoms, e.g. pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, indazolyl, purinyl, 4H-quinolizinyl, isoquinolyl, quinolyl, phthalazinyl, naphtyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4H-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, 7H-pyrazino[2,3-c]carbazolyl, imidazo[1 ,2-b][1 ,2,4]triazinyl and pyrido[1 ',2':1 ,2]innidazo[4,5-b]quinoxalinyl.
- heteroaromatic rings with one to four nitrogen atoms and one or more further heteroatoms, e.g. phenarsazinyl, isothiazolyl, phenothiazinyl, isoxazolyl, furazinyl, phenoxazinyl, 5H-pyrido[2,3-d]oxazinyl, 1 H- pyrazolo[4,3-d]oxazolyl, 4H-imidazo[4,5-d]thiazolyl, selenazolo[5,4- f]benzothiazolyl, pyrazino[2,3-d]pyridazinyl, imidazo[2,1 -b]thiazolyl, furo[3,4-c]cinnolinyl, 4H-pyrido[2,3-c]carbazolyl, 4H-[1 ,3]oxathiolo-[5,4- b]pyrrolyl and 4H-1 ,3-dioxolo[4,5-d]imidazolyl.
Exemplary compounds of this group include, but are not limited to, 2- pyridinesulfonic acid, 3-pyridinesulfonic acid, 4-pyridinesulfonic acid, 4- quinolinesulfonic acid, and 8-quinolinesulfonic acid.
According to another embodiment, the present invention relates to zwitterionic compounds including a structural moiety represented by the generic formula 2 wherein Het represents a heteroaromatic ring such as, but not limited to, a pyridinyl ring or a quinolinyl ring, and the sulfonate anion is attached to said heteroaromatic ring through a linker being an aliphatic chain with 1 to 4 carbon atoms, i.e. p is 1 to 4. Suitable examples of the heteroaromatic ring are as listed above. Each of the above-mentioned sub-groups of zwitterionic compounds is useful as a catalyst for use in a process for the preparation of an organic ester by reacting a carboxylic acid or an anhydride with an alcohol. Each aspect of this process, including the kind of suitable starting materials, is described in details below.
The carboxylic acid or anhydride used in the process for producing esters according to the present invention is not particularly limited. Suitable examples thereof include: monocarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms such as, but not limited to, acetic acid, propionic acid, butyric acid, valeric acid, n-hexanoic (caproic) acid, heptanoic (enanthic) acid, octanoic (caprylic) acid, n-nonanoic (pelargonic) acid, n-decanoic (capric) acid, n-dodecanoic (lauric) acid, n-tetradecanoic (myristic) acid, n-octadecanoic (stearic) acid, acetic anhydride, propionic anhydride, butyric anhydride, valeric anhydride and n-hexanoic (caproic) anhydride;
monocarboxylic acids including saturated aliphatic acids having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is directly or indirectly (i.e. via a linking heteroatom such as oxygen) substituted with an aromatic ring such as, but not limited to, phenylacetic acid, phenylpropionic acid, 2-phenylbutyric acid, 3-phenylbutyric acid, 4- phenylbutyric acid, 5-phenylvaleric acid, 6-phenylhexanoic acid, 7-phenyl- heptanoic acid, 8-phenyloctanoic acid, 9-phenylnonanoic acid, 10-phenyl- decanoic acid, 12-phenyldodecanoic acid, 16-phenylhexadecanoic acid, 18-phenyl octadecanoic acid, 1 -naphthylacetic acid, 2-naphthylacetic acid, 3-(1 -naphthyl)propionic acid, phenoxyacetic acid, 1 -naphthoxyacetic acid and 2-naphthoxyacetic acid;
monocarboxylic or dicarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is substituted with a saturated or ethylenically unsaturated cycloaliphatic group such as, but not limited to, cyclohexylacetic acid, 1 ,1 -cyclohexanediacetic acid, 4-cyclohexylbutyric acid, 5-cyclohexylvaleric acid, cyclopentylacetic acid, 1 ,1 - cyclopentanediacetic acid, 3-cyclopentylpropionic acid, 2-cyclopentene-1 - acetic acid, 2-ethylhexanoic acid, cyclohexene-1 ,2-dicarboxylic (tetrahydrophthalic) anhydride;
ethylenically unsaturated fatty acids or anhydrides having from 8 to 24 carbon atoms, such as, but not limited to, oleic acid, 2-octenoic acid and nervonic acid;
dicarboxylic saturated aliphatic acids or anhydrides having from 2 to 12 carbon atoms, such as, but not limited to, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, and dodecanedioic acid;
- dicarboxylic ethylenically unsaturated acids or anhydrides having from 4 to 12 carbon atoms, such as, but not limited to, fumaric acid, maleic acid, trans-3-hexenedioic (dihydromuconic) acid, and 2-dodecenedioic (trans- traumatic) acid;
- dicarboxylic aromatic acids or anhydrides such as, but not limited to, terephthalic acid, isophthalic acid, and diphenyl ether-4,4' -dicarboxylic acid;
- tricarboxylic acids or anhydrides such as, but not limited to, butane-1 ,2,4- tricarboxylic acid, cyclohexane-1 ,2,3-tricarboxylic acid, cyclohexane-1 ,3,5- tricarboxylic acid, benzene-1 ,2,4-tricarboxylic acid, and naphthalene-1 ,2,4- tricarboxylic acid;
- tetracarboxylic acids or anhydrides such as, but not limited to, butane- 1 ,2,3,4-tetracarboxylic acid, cyclobutane-1 ,2,3,4-tetracarboxylic acid, benzene-1 , 2,4, 5-tetracarboxylic acid, 3,3',4,4'-benzophenone tetracarboxylic acid, and 3,3',4,4'-diphenyl ether tetracarboxylic acid;
- cycloaliphatic saturated and ethylenically unsaturated monocarboxylic or dicarboxylic acids or anhydrides, e.g. cyclohexanecarboxylic acid, cyclopentane-carboxylic acid, 1 ,2-cyclopentanedicarboxylic acid and cyclohexene-carboxylic acid;
- ethylenically unsaturated non-fatty acids or anhydrides such as, but not limited to, acrylic acid, methacrylic acid and methacrylic anhydride;
- acetylenically unsaturated acids having from 3 to 12 carbon atoms, e.g. propiolic acid, 2-butynoic acid, 4-pentynoic acid or 2-octynoic acid;
monocarboxylic aromatic acids or anhydrides, e.g. benzoic acid, 4- pentylbenzoic acid;
These carboxylic acids may have, on the aliphatic chain or the aromatic chain thereof, one or more functional substituents not interfering with the esterification reaction, e.g. functional substituents independently selected from the group consisting of Ci-4 alkyl, Ci-4 alkoxy, nitro, cyano, halogen, fluoro-Ci-4 alkyl and fluoro-Ci-4 alkoxy. An exemplary group of such functional carboxylic acids comprises substituted phenylacetic acids such as, but not limited to, 4- bromophenylacetic acid, 3-bromophenylacetic acid, 2-bromophenylacetic acid, 4-chlorophenylacetic acid, 3-chlorophenylacetic acid, 2-chlorophenylacetic acid, 4-fluorophenylacetic acid, 3-fluorophenylacetic acid, 2-fluorophenylacetic acid, 4-nitrophenylacetic acid, 3-nitrophenylacetic acid, 2-nitrophenylacetic acid, 2,4-dichlorophenylacetic acid, 2,6-dichloro-phenylacetic acid, 3,4- dichlorophenylacetic acid, 4-methoxyphenylacetic acid, 3- methoxyphenylacetic acid, 2-methoxyphenylacetic acid, 4-methylphenyl-acetic acid (p-tolylacetic acid), 3-methylphenylacetic acid (m-tolylacetic acid), 2- methylphenylacetic acid (o-tolylacetic acid), 2,4,6-trimethylphenylacetic acid (mesitylacetic acid), 4-isopropylphenylacetic acid (cumenylacetic acid), A-n- propylphenylacetic acid, 3,5-dimethylphenylacetic acid, 2,5-dimethylphenyl- acetic acid, 3,4-dimethylphenylacetic acid, 2,4-dimethylphenylacetic acid, 4-n- butoxyphenylacetic acid, 4-n-propoxyphenylacetic acid, 4-ethoxyphenylacetic acid, 2-ethoxyphenylacetic acid, 4-n-butylphenylacetic acid, 4-isobutyl- phenylacetic acid, 4-fe/ -butyl phenylacetic acid, 3,4-dimethoxyphenylacetic acid, 2,5-dimethoxyphenylacetic acid, 2,3-dimethoxyphenylacetic acid, 3,5- dimethoxy-phenylacetic acid, 2,4-dimethoxyphenylacetic acid and 3,4- diethoxyphenylacetic acid. Another exemplary group of such functional carboxylic acids comprises substituted phenylpropionic acids such as, but not limited to, 3-(2-iodophenyl)propionic acid, 3-(2-bromophenyl)propionic acid, 3- (2-chlorophenyl)propionic acid, 3-(2-fluorophenyl)propionic acid, 3-(3- iodophenyl)propionic acid, 3-(3-bromophenyl)propionic acid, 3-(3- chlorophenyl)propionic acid, 3-(3-fluorophenyl)propionic acid, 3-(4- iodophenyl)propionic acid, 3-(4-bromophenyl)propionic acid, 3-(4- chlorophenyl)propionic acid, 3-(4-fluorophenyl)propionic acid, 2-(4- chlorophenyl)propionic acid, 2-(2-chlorophenyl)propionic acid, 3-(4- nitrophenyl)propionic acid, 3-(3-nitrophenyl)propionic acid, 3-(4- methoxyphenyl)propionic acid, 3-(3-methoxyphenyl)propionic acid, 3-(2- methoxyphenyl)propionic acid, 3-(3,4-dimethoxyphenyl)propionic acid, 3-(3,5- dimethoxyphenyl)propionic acid, 3-(2,4-dimethoxyphenyl)propionic acid, 3- (2,3-dimethoxyphenyl)propionic acid, 3-(2,5-dimethoxyphenyl)propionic acid, 3-(4-ethoxyphenyl)propionic acid, 3-(3-ethoxyphenyl)propionic acid, 3-(4- propoxyphenyl)propionic acid, 2-(2,3-dichlorophenyl)propionic acid, 3-(2,3- dichlorophenyl)propionic acid, 3-(2,4-dichlorophenyl)propionic acid, 3-(2,6- dichlorophenyl)propionic acid, 3-(3,4-dichlorophenyl)propionic acid, 3-(2,4- difluorophenyl)propionic acid, 3-(3,4-difluorophenyl)propionic acid, 3-[3- (trifluoronnethyl)phenyl]propionic acid, 3-(4-methylphenyl)propionic acid, 3-(3- methylphenyl)propionic acid, 3-(2-methylphenyl)propionic acid, 3-(2,4- dimethylphenyl)propionic acid, 3-(3,4-dimethylphenyl)propionic acid, 3-(2,5- dimethylphenyl)propionic acid, 3-(4-ethylphenyl)propionic acid, and 3-(4- isopropylphenyl)propionic acid.
Another exemplary group of such functional carboxylic acids comprises substituted benzoic acids such as, but not limited to, 2-chlorobenzoic acid, 3- chlorobenzoic acid, 4-chlorobenzoic acid, 2-bromobenzoic acid, 3- bromobenzoic acid, 4-bromobenzoic acid, 2-fluorobenzoic acid, 3- fluorobenzoic acid, 4-fluorobenzoic acid, 4-aminobenzoic acid, 4-amino-5- chloro-2-methoxybenzoic acid, 4-amino-2-chlorobenzoic acid or 4-amino-3- nitrobenzoic acid.
The alcohol used in the process for producing esters according to the present invention is not particularly limited. Suitable examples thereof include: - saturated aliphatic monohydric alcohols such as, but not limited to, methanol, ethanol, propanol, butanol, pentanol, hexanol, heptanol, octanol, decanol, undecanol, dodecanol, nonanol, 2-ethylhexanol, 2-heptylheptanol and stearyl alcohol;
- alicyclic monohydric alcohols such as, but not limited to, cyclohexanol and cyclododecanol;
- aromatic monohydric alcohols such as, but not limited to, benzyl alcohol;
- polyhydric alcohols such as, but not limited to, ethylene glycol, propylene glycol, neopentyl glycol, trimethylol propane, trimethylol ethane, pentaerythritol, dipentaerythritol, sorbitol, and polyvinyl alcohol;
- alicyclic dihydric alcohols such as, but not limited to, cyclohexane-1 ,2-diol and cyclopentane-1 ,2-diol; and
- ethylenically unsaturated aliphatic monohydric alcohols such as, but not limited to, allyl alcohol. These alcohols may be primary alcohols or secondary alcohols. One or more functional groups not interfering with the esterification reaction, e.g. functional groups independently selected from the group consisting of Ci-4 alkoxy, nitro, cyano, halogen, fluoro-Ci-4 alkyl and fluoro-Ci-4 alkoxy, may be present on the aliphatic chain of the alcohol. However a functional group containing a nitrogen atom, such as an amino group, may be capable of interfering with the esterification reaction by deprotonating the catalyst of the invention, and consequently should be avoided.
In the process for producing esters according to the present invention, although the reaction proceeds when either one of the carboxylic acid or the alcohol is used in a molar excess amount, the reaction also suitably proceeds when equimolar amounts of the carboxylic acid and the alcohol are used. It is accordingly an object of the present invention to provide a process for the preparation of an organic ester by reacting a carboxylic acid or anhydride with an alcohol in the presence of a zwitterionic catalyst as defined herein and wherein equimolar amounts of the carboxylic acid and the alcohol are used.
The process for the preparation of organic esters as provided herein, may proceed in the absence of a reaction solvent. In a particular embodiment the process for producing esters according to the present invention will proceed in the presence of at least one solvent. The reaction solvent optionally used in the process of this invention is not particularly limited as long as it is inactive in the esterification reaction. The reaction solvent may be a non-polar solvent or a polar solvent; it can either form a homogeneous or biphasic mixture at the start or end of the reaction at any given temperature. If it forms at the end of the reaction a biphasic mixture, it can act as a water and/or catalyst removal in particular when a polar ionic liquid is used with physicochemical properties suited for this purpose.
Suitable examples of the reaction solvent include:
- aliphatic and cycloaliphatic saturated hydrocarbons such as, but not limited to, hexane, heptane, cyclohexane, methylcyclohexane, octane, and mixtures thereof;
- halogenated alkanes, such as, but not limited to, methylene chloride, chloroform, carbon tetrachloride, and ethylene chloride; - aromatic hydrocarbons such as, but not limited to, benzene, toluene, xylene, mesitylene, and pentamethylbenzene;
- halogenated aromatic hydrocarbons, such as, but not limited to, chlorobenzene and bromobenzene;
- ethers, such as, but not limited to, diethyl ether, anisole, THF, 2-MeTHF, 1 ,4-dioxane, (EtO)2CH2, and MBTE; and
Ionic Liquids, such as but not limited to EMIM CI (1 -Ethyl-3- methylimidazolium chloride), BMIM CI (1 -Butyl-3-methylimidazolium chloride), EMIM MeSO3 (1 -Ethyl-3-methyl imidazolium methanesulfonate), EMIM EtOSO3 (1 -Ethyl-3-methyl imidazolium ethylsulfate) EMIM DEP (1 -Ethyl-3- methyl imidazolium diethylphosphate), EMIM DCA (1 -Ethyl-3-methyl imidazolium dicyanamide) EMIM OAc (1 -Ethyl-3-methyl imidazolium acetate) MTEOA MeOSO3 (Tris-(2-hydroxyethyl)-methylammonium methylsulfate), EMIM BF4 (1 -Ethyl-3-methyl imidazolium tetrafluoroborate), EMIM OTf (1 - Ethyl-3-methyl imidazolium trifluoromethanesulfonate), EMIM TFSI (1 -Ethyl-3- methyl imidazolium bis (trifluormethanesulfonyl)imide, CYPHOS IL Phosphonium salts, 1 -Allyl-3-methylimidazolium chloride, 1 -n-Butyl-3- methylimidazolium bromide, 1 -n-Butyl-3-methylimidazolium chloride, 1 -n- Butyl-3-methylimidazolium hexafluoroantimonate, 1 -n-Butyl-3- methylimidazolium hexafluorophosphate, 1 -n-Butyl-3-methylimidazolium methanesulfonate, 1 -n-Butyl-3-methylimidazolium methylsulfate, 1 -n-Butyl-3- methylimidazolium n-octylsulfate, 1 -n-Butyl-3-methylimidazolium tetrafluoroborate, 1 -n-Butyl-3-methylimidazolium trifluoromethanesulfonate, 1 ,3-Dimethylimidazolium dimethylphosphate, 1 -Ethyl-3-methylimidazolium bromide, 1 -Ethyl-3-methylimidazolium dicyanamide, 1 -Ethyl-3- methylimidazolium diethylphosphate, 1 -Ethyl-3-methylimidazolium ethylsulfate, 1 -Ethyl-3-methylimidazolium hexafluorophosphate, 1 -Ethyl-3- methylimidazolium hydrogen sulfate, 1 -Ethyl-3-methylimidazolium methanesulfonate, 1 -Ethyl-3-methylimidazolium tetrafluoroborate, 1 -Ethyl-3- methylimidazolium trifluoromethanesulfonate, 1 -n-Hexyl-3-methylimidazolium chloride, 1 -n-Hexyl-3-methylimidazolium hexafluorophosphate, 1 -n-Hexyl-3- methylimidazolium tetrafluoroborate, 1 -Methyl-3-n-octylimidazolium tetrafluoroborate, 1 -Methyl-3-n-propylimidazolium iodide, In one embodiment of the present invention the process for the preparation of an organic ester is performed in the presence of a solvent selected from the group consisting of an aliphatic saturated hydrocarbon, a cycloaliphatic saturated hydrocarbon or an aromatic hydrocarbon.
The amount of the zwitterionic compound used as a catalyst in the process for producing esters according to the present invention is appropriately set depending on the esterification reaction system (i.e. types of carboxylic acid and alcohol used as reactants, type of reaction solvent, etc.), using general knowledge of the person skilled in the art. For example, the zwiterionic compound may be used in an amount ranging from about 0.01 % to about 20 mole %, in particular from about 0.1 % to about 10 mole %, more particularly from about 0.2% to about 5 mole % with respect to the amount of carboxylic acid or anhydride or the amount of alcohol, whichever is lower.
In the process for producing esters according to the present invention, the reaction temperature and the reaction time are appropriately set depending on the esterification reaction system (i.e. the type of carboxylic acid or anhydride and the type of alcohol used as reactants, type of reaction solvent, etc.), using general knowledge of the person skilled in the art. For example, the reaction temperature may be ranging from about 10 °C to about 180 °C, in particular from about 20 °C to about 100 °C. In a particular embodiment of this invention, when a primary alcohol is used, the esterification reaction may proceed at room temperature in the absence of a solvent. The reaction is carried out for a period of time after which a predetermined molar amount of the desired ester has been formed, or until either the carboxylic acid or the alcohol has substantially disappeared. The reaction time usually ranges from about 0.5 hour to about 72 hours.
If desired, water produced by the esterification reaction may be actively removed from the reaction system, either continuously or discontinuously, using general knowledge of the person skilled in the art. Evidently, within the context of the present invention the process for producing organic esters as provided herein may be allowed to proceed either with or without removing produced water from the reaction mixture. In one embodiment of the process for producing esters according to the present invention, the esterification catalyst may be separated from the reaction mixture after esterification has been substantially completed and may be reused a significant number of times without losing activity or selectivity.
In each of the foregoing embodiments with the removal of the water and/or the removal of the catalyst the process for the preparation of an organic ester may be performed in the presence of a solvent that phase separates after the reaction and can contain water and/or the catalyst in one of said phase. Exemplary solvents to be used in this embodiment include ionic liquids such as EMIM CI (1 -Ethyl-3-methylimidazolium chloride), BMIM CI (1 -Butyl-3- methylimidazolium chloride), EMIM MeSO3 (1 -Ethyl-3-methyl imidazolium methanesulfonate), EMIM EtOSO3 (1 -Ethyl-3-methyl imidazolium ethylsulfate) EMIM DEP (1 -Ethyl-3-methyl imidazolium diethylphosphate), EMIM DCA (1 - Ethyl-3-methyl imidazolium dicyanamide) EMIM OAc (1 -Ethyl-3-methyl imidazolium acetate) MTEOA MeOSO3 (Tris-(2-hydroxyethyl)- methylammonium methylsulfate), EMIM BF (1 -Ethyl-3-methyl imidazolium tetrafluoroborate), EMIM OTf (1 -Ethyl-3-methyl imidazolium trifluoromethanesulfonate), EMIM TFSI (1 -Ethyl-3-methyl imidazolium bis (trifluormethanesulfonyl)imide, CYPHOS IL Phosphonium salts, 1 -Allyl-3- methylimidazolium chloride, 1 -n-Butyl-3-methylimidazolium bromide, 1 -n- Butyl-3-methylimidazolium chloride, 1 -n-Butyl-3-methylimidazolium hexafluoroantimonate, 1 -n-Butyl-3-methylimidazolium hexafluorophosphate, 1 - n-Butyl-3-methylimidazolium methanesulfonate, 1 -n-Butyl-3- methylimidazolium methylsulfate, 1 -n-Butyl-3-methylimidazolium n- octylsulfate, 1 -n-Butyl-3-methylimidazolium tetrafluoroborate, 1 -n-Butyl-3- methylimidazolium trifluoromethanesulfonate, 1 ,3-Dimethylimidazolium dimethylphosphate, 1 -Ethyl-3-methylimidazolium bromide, 1 -Ethyl-3- methylimidazolium dicyanamide, 1 -Ethyl-3-methylimidazolium diethylphosphate, 1 -Ethyl-3-methylimidazolium ethylsulfate, 1 -Ethyl-3- methylimidazolium hexafluorophosphate, 1 -Ethyl-3-methylimidazolium hydrogen sulfate, 1 -Ethyl-3-methylimidazolium methanesulfonate, 1 -Ethyl-3- methylimidazolium tetrafluoroborate, 1 -Ethyl-3-methylimidazolium trifluoromethanesulfonate, 1 -n-Hexyl-3-methylimidazolium chloride, 1 -n-Hexyl- 3-methylinnidazoliunn hexafluorophosphate, 1 -n-Hexyl-3-methylimidazoliunn tetrafluoroborate, 1 -Methyl-3-n-octylimidazoliunn tetrafluoroborate, 1 -Methyl-3- n-propylimidazoliunn iodide,
According to another embodiment, the present invention relates to certain methods for producing the zwitterionic compounds that are used as esterification catalysts. Such methods are illustrated in the single appended figure 1
Both methods shown in figure 1 include the combination of a sulfonation step and a coupling step, however in different order. A first method (shown on the right side of the figure) involves the sulfonation of a starting material bearing an ammonium cation, followed by the coupling of the resulting intermediate with a Rrcontaining reactant RiX wherein X may be selected from the group consisting of iodo, bromo, chloro, triflate, B(OH)2 and BF3K.
According to one embodiment, the present invention relates to a method for producing /V-aryl-sulfanilic acids, /V-aryl-orthanilic acids, /V-aryl-metanilic acids and 5-(/V-arylamino)-o-toluenesulfonic acids wherein an aryl iodide is reacted, in the presence of a base such as an alkaline alkoxide and a catalytic amount of a transition metal complex of an organophosphorous ligand, with sulfanilic acid, orthanilic acid, metanilic acid or 5-amino-o-toluenesulfonic acid, respectively. The method of this particular embodiment may be performed in an organic solvent such as an ether, e.g. a cyclic ether. The method of this particular embodiment may be performed at a temperature ranging from about 40°C to about 140°C for a period of time ranging from about 4 to 78 hours. The transition metal complex used in the method of this particular embodiment may be a complex of copper, nickel, iron or palladium. The organophosphorous ligand used in the method of this particular embodiment may be a -ligand such as, but not limited to, (±)-2,2'-bis(diphenylphosphino)-1 ,1 '- binaphthyl (racemic) (BINAP). Bases that may be used in the method of this particular embodiment include, but are not limited to, sodium terf-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide and potassium hydroxide. Aryl iodides that may be used in the method of this particular embodiment include, but are not limited to, phenyl iodide, naphthyl iodide, 2-iodotoluene, 3-iodotoluene, 4-iodotoluene, iodomesitylene, 1 -iodo- 2,3-dimethylbenzene, 1 ,4-dimethyl-2-iodobenzene, 2-iodo-m-xylene, 4-iodo- m-xylene, 5-iodo-m-xylene and 4-iodo-o-xylene.
According to another embodiment, the present invention relates to a method for producing /V-substituted sulfanilic acids, comprising reacting a N- substituted aniline derivative or Λ/,/V-disubstituted aniline derivative with a non- acidic sulfonating agent. The method of this particular embodiment may be performed in the presence or absence of an organic solvent. The method of this particular embodiment may be performed at a temperature ranging from about 40°C to about 180°C for a period of time ranging from about 1 hour to about 48 hours. The non-acidic sulfonating agent may be bis(trimethylsilyl) sulfate, sulfuric acid or chlorosulfonic acid.
Hereinafter, non limiting examples of zwitterionic compounds that may be made by one or more of the above methods are provided.
EXAMPLE 1
Bistrimethylsilyl sulfate (1 molar equiv.) and an aniline derivative (1 molar equiv.) were placed in a round bottom flask equipped with a reflux condenser. The mixture was stirred at 170°C for the time period (expressed in hours) indicated in table 1 . The pasty solid obtained was washed with ether. Subsequent basic and/or acid work-ups were performed depending upon the purity of the compound obtained.
Table 1 shows the sulfonated aniline derivative yield (expressed as %) obtained after a certain period of time (expressed in hours).
Table 1
Figure imgf000028_0001
Figure imgf000029_0001
EXAMPLE 2
3-phenylpropanoic acid (760 mg, 5.06 mmol), ethanol (0.5 ml, 8.6 mmol), toluene (5 ml), dodecane (1 14 μΙ, 0.5 mmol) as an internal standard, and the catalyst (0.15 mmol) were added in a round-bottom flask with a reflux condenser. The reaction mixture was stirred at 90°C in an oil bath for five hours. The reaction was followed by Gas Chromatography coupled to a Mass Spectrometer detector using a Finnigan Trace2000 equipped with a Varian FactorFour (30m x 0,25mm; ID; DF=10) column. Table 2 shows the yield of 3-phenylpropanoic ethanoate (expressed %) obtained after a certain period of time (expressed in hours). Entry 1 given for comparative purpose.
Table 2
Figure imgf000030_0002
EXAMPLE 3
Benzoic acid (648 mg, 5.06 mmol), cyclohexanol (507 mg, 5.07 mmol), toluene (5 ml), dodecane (1 14 μΙ, 0.5 mmol) and 4- (phenylamino)benzenesulfonic acid (40 mg, 0.15 mmol) were added in a round round-bottom flask with a reflux condenser. The reaction mixture was stirred at 90°C in an oil bath for 24 hours. The reaction was followed by Gas Chromatography coupled to a Mass Spectrometer detector using a Finnigan Trace2000 equipped with a Varian FactorFour (30m x 0,25mm; ID; DF=10) column.
After 24h, Cyclohexyl benzoate was produced in a more than 95% yield.
Figure imgf000030_0001
3-phenyl propionic acid (760 mg, 5.06 mmol) was added to ethanol (1 .2 ml, 21 mmol). In order to have a homogeneous solution, the reaction mixture was heated at 80°C. After, the catalyst (25 mg) was added to the solution. The reaction mixture was heated at 80°C for several hours. The reaction was followed by Gas Chromatography coupled to a Mass Spectrometer detector using a Finnigan Trace2000 equipped with a Varian FactorFour (30m x 0,25mm; ID; DF=10) column.
Table 3 shows the yield of 3-phenylpropanoic ethanoate (expressed as %) obtained after a certain period of time (expressed in hours). Entry 1 is given for comparative purpose.
Table 3
Figure imgf000031_0001
EXAMPLE 5
Procedure A: 3-phenylpropanoic acid (760 mg, 5.06 mmol), ethanol (0.5 ml, 8.6 mmol), toluene (5 ml), dodecane (1 14 μΙ, 0.5 mmolj as an internal standard, and the catalyst (0.15 mmol) were added in a round-bottom flask with a reflux condenser. The reaction mixture was stirred at 90°C in an oil bath for several hours. The reaction was followed by Gas Chromatography coupled to a Mass Spectrometer detector using a Finnigan Trace2000 equipped with a Varian FactorFour (30m x 0,25mm; ID; DF=10) column.
Procedure B: 3-phenyl propionic acid (760 mg, 5.06 mmol) was added to ethanol (2 ml, 34 mmol). In order to have a homogeneous solution, the reaction mixture was heated at 80°C. The catalyst (0.2 mmol) was added to the solution and the reaction mixture was heated at 80°C for several hours. The reaction was followed by Gas Chromatography equipped with a Varian FactorFour (30m x 1 mm; ID; DF=10) column and coupled to a FID detector. Table 4 shows the yield of 3-phenylpropanoic ethanoate (expressed %) obtained after a certain period of time (expressed in hours).
Table 4
Figure imgf000032_0001
Figure imgf000033_0001
14 B 24 13
Quinoline-8-sulfonic acid
EXAMPLE 6
Acid (5.06 mmol), alcohol (8.6 mmol), toluene (5 ml), dodecane (1 14 μΙ, 0.5 mmol) as an internal standard, and catalyst (0.15 mmol) were added in a round-bottom flask with a reflux condenser. The reaction mixture was stirred at 90°C in an oil bath for several hours. The reaction was followed by Gas Chromatography coupled to a Mass Spectrometer detector using a Finnigan Trace2000 equipped with a Varian FactorFour (30m x 0,25mm; ID; DF=10) column.
Table 5 shows the yield of ester (expressed as %) obtained after a certain period of time (expressed in hours).
Table 5
Figure imgf000034_0001
EXAMPLE 7
3-phenylpropionic acid (2.2 g, 40.6 mmol) was added to ethanol (4 ml, 69.5 mmol). In order to have a homogeneous solution, the reaction mixture was heated at 80°C. After 2 minutes, ortho-anilic acid (120 mg, 5 mole %) was added to the solution and the reaction mixture was heated at 80°C. After 14 hours, the reaction mixture was cooled down at room temperature and a white solid precipitated. The white solid was filtrated off and washed with 2 ml of hexane. The organic layer was concentrated under vacuum and gives us 2,27g (87 %) of the desired ester.
EXAMPLE 8 - production of /V-aryl-ortho-sulfanilic acids
The production of /V-aryl-ortho-sulfanilic acids (represented by the structural formula 8, wherein Ar designates an aryl group as defined herein- above) proceeds according to the scheme shown below.
Figure imgf000035_0001
A 25-mL, round-bottomed flask equipped with a magnetic stirring bar and a septum was dried and allowed to cool to room temperature under a nitrogen balloon. The flask was charged with sodium terf-butoxide (2.5 molar equiv., 650 mg) (3), dioxane (8 mL) (6), water (2 mL) (7), ortho-anilinic acid (1 .3 molar equiv.) (2), an aryl iodide (1 molar equiv.) (1) and (±)-BINAP (0.014 molar equiv., 23 mg).(4) The septum was placed on the flask, and the flask was purged with nitrogen for about 20 minutes. The flask was charged with bis(dibenzylideneacetone)palladium(0) (0.007 molar equiv., 1 1 mg) (5). The septum was replaced by a condenser with a nitrogen balloon. The resulting red solution was placed in an oil bath that was heated at reflux with stirring. After 48 hours, the reaction mixture was added to water (10 mL) and dichloromethane (10 mL). The water phase was separated and concentrated under vacuum. The resulting brown solid was poured into ethanol (20 mL). The resulting white solid was filtered off and the ethanolic phase was concentrated under vacuum and provided the desired compounds as solids in about 10-20% yields depending upon the exact nature of the aryl group Ar. Example 9 - production of /V-aryl-para-sulfanilic acids
The production of /V-aryl-para-sulfanilic acids (represented by the structural formula 7, wherein Ar designates an aryl group as defined hereinabove) proceeds according to the scheme shown below.
(3) NaOtB u
(4) BINAP
(5) Pd(dba)2
Ar- 1 H2N— <^ Vso3H (6) Toluene ^ Ar_N_^^_So3H
1 2 7
A 25-mL, round-bottomed flask equipped with a magnetic stirring bar and a rubber septum was dried and allowed to cool to room temperature under a nitrogen balloon. The septum was removed and the flask was charged with sodium terf-butoxide (2.3 molar equiv., 1 .1 g), toluene (8 ml_), sulfanilic acid (1 .2 molar equiv.), an aryl iodide (1 molar equiv.) and (±)-BINAP (0.014 molar equiv., 23 mg). The septum was again placed on the flask, and the flask was purged with nitrogen for about 20 minutes. The flask was charged with bis(dibenzylideneacetone)palladium(0) (0.007 molar equiv., 1 1 mg). The resulting dark red mixture was placed in an oil bath that was heated to 80°C. The reaction was monitored by LC/MS, using Agilent 1 100 fitted with a column Agilent Zorbax Eclipse C8 (analytical, 4.6 x 150 mm, 5 μ).

Claims

1 . A process for the preparation of an organic ester, comprising reacting a carboxylic acid or anhydride with an alcohol in the presence of a zwitterionic catalyst, and separating the ester formed from the reaction mixture, wherein said zwitterionic catalyst contains an ammonium cation and a sulfonate anion and is generally represented by formula 1
Figure imgf000037_0001
wherein:
- Ri and R'i are independently selected from the group consisting of hydrogen, Ci-4 alkyl, and aryl optionally substituted with one, two or more Ci-4 alkyl substituents;
- R4 is independently hydrogen or CMO alkyl;
- p is 0 to 8;
- L represents a direct bond, a bivalent radical of the formula
Figure imgf000037_0002
R2 wherein - R2 is independently hydrogen or CMO alkyl;
- m is 0 to 4; n is 0 or 1 ;
- Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci-4 alkyl, aryl, benzyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, , aryloxy, Ci-4 alkylthio, arylthio and fluoro-Ci-4 alkoxy; or
- L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring;
provided that ; - when the sum of m, n and p is 0, then at least one of Ri and R'i does not represent hydrogen;
- when L represents the bivalent radical of formula (a1 ), and Ar represents napthyl, then the ammonium cation group and the sulfonate anion group are at positions 1 and 8 of the naphtyl residue;
- when L represents the bivalent radical of formula (a1 ), m is 0, n is 1 , Ar represents phenyl, at least one of Ri and R'i does not represent hydrogen, and p is 0, then the ammonium cation group and the sulfonate anion group are present in ortho position of one another; and
provided that said zwitterionic catalyst is not p-sulfanilic acid or m-sulfanilic acid, in particular when used as a catalyst for the esterification of :
- stearic acid with glycol,
- citric acid with a fatty alcohol,
- acetic acid with isoamyl alcohol,
- benzoic acid or adipic acid with n-hexyl alcohol, or
- phthalic anhydride with an alcohol having from 7 to 9 carbon atoms.
2. A process according to claim 1 , being performed at a temperature from about 10°C to about 180°C; in particular at a temperature from about 40°C to about 140°C; more in particular at a temperature from about 60°C to about 100°C.
3. A process according to claim 1 or claim 2, being performed for a time period ranging from 0.5 hour to 72 hours; in particular from 1 hour to 48 hours.
4. A process according to any one of claims 1 to 3, wherein the amount of zwitterionic catalyst used ranges from about 0,01 % to about 20 mole % with respect to the amount of carboxylic acid or anhydride, or the amount of alcohol, whichever is lower.
5. A process according to any one of claims 1 to 4, wherein equimolar amounts of the carboxylic acid and the alcohol are used.
6. A process according to any one of claims 1 to 5, wherein the process for the preparation of an organic ester is performed in the presence of a solvent selected from the group consisting of an aliphatic saturated hydrocarbon, a cycloaliphatic saturated hydrocarbon or an aromatic hydrocarbon.
7. A process according to any one of claims 1 to 5, wherein the process for the preparation of an organic ester is performed in the presence of a solvent that phase separates after the reaction and can contain water and/or the catalyst in one of said phases.
8. A process according to any of claims 1 to 7, wherein said zwitterionic catalyst is generally represented by the formula 2
Figure imgf000039_0001
2
wherein:
- Het designates a heteroaromatic ring structure containing one to four nitrogen atoms and a total of 5 to 17 ring atoms,
- each R5 is independently selected from the group consisting of hydrogen, C-1 -4 alkyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, Ci-4 alkylthio and fluoro-Ci-4 alkoxy,
- each R is independently selected from the group consisting of hydrogen and C-1-10 alkyl, and
- p is 0 to 8; in particular p is 0 to 4.
9. A process according to claim 8, wherein said zwitterionic catalyst is generally represented by the formula 2 and wherein;
- Het designates a heteroaromatic ring structure containing one nitrogen atom; more in particular Het designates a heterocyclic iminium cation; even more in particular Het designates a pyridinium ring;
- R5 is hydrogen;
- R is hydrogen, and
- p is 0 to 8; in particular p is 0 to 4.
10. A process according to any one of claims 1 to 9, wherein said zwitterionic catalyst is selected from the group consisting of;
- 5-methyl-2-(p-tolylamino)benzenesulfonic acid;
- o-sulfanilic acid;
- 4-(phenylamino)benzenesulfonic acid;
- 4-(dimethylamino)benzenesulfonic acid;
- 2-aminonaphthalene-1 -sulfonic acid;
- 4-(ethylamino)benzenesulfonic acid;
- 2-amino-4-methylbenzenesulfonic acid;
- 2-(phenylamino)ethanesulfonic acid;
- 8-aminonaphthalene-1 -sulfonic acid;
- 8-(phenylamino)naphthalene-1 -sulfonic acid;
- (2-(phenylamino)phenyl)methanesulfonic acid;
- pyridine-2-sulfonic acid;
- 3-Pyridinesulfonic acid;
- 4-Pyridineethanesulfonic acid; and
- Quinoline-8-sulfonic acid;
1 1 . A process according to any one of claims 1 to 10, wherein the carboxylic acid or anhydride is selected from the group consisting of:
- monocarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms; - monocarboxylic acids including saturated aliphatic acids having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is directly or indirectly substituted with an aromatic ring;
- monocarboxylic or dicarboxylic acids including saturated aliphatic acids or anhydrides having from 2 to 18 carbon atoms in the aliphatic chain and wherein the aliphatic chain is substituted with a saturated or ethylenically unsaturated cycloaliphatic group;
- ethylenically unsaturated fatty acids having from 8 to 24 carbon atoms;
- dicarboxylic saturated aliphatic acids having from 2 to 12 carbon atoms;
- dicarboxylic ethylenically unsaturated acids having from 4 to 12 carbon atoms;
- dicarboxylic aromatic acids;
- tricarboxylic acids;
- tetracarboxylic acids;
- cycloaliphatic saturated and ethylenically unsaturated monocarboxylic or dicarboxylic acids;
- ethylenically unsaturated non-fatty acids or anhydrides;
- acetylenically unsaturated acids having from 3 to 12 carbon atoms; and monocarboxylic aromatic acids;
and wherein said carboxylic acid optionally has, on the aliphatic chain or the aromatic chain thereof, one or more functional substituents not interfering with the esterification reaction.
12. A process according to any one of claims 1 to 10, wherein said alcohol is selected from the group consisting of :
- saturated aliphatic monohydric alcohols;
- alicyclic monohydric alcohols;
- alkylaromatic monohydric alcohols;
- polyhydric alcohols;
- alicyclic dihydric alcohols;
- ethylenically unsaturated aliphatic monohydric alcohols;
and wherein said alcohol optionally has, on the aliphatic chain thereof, one or more functional substituents not interfering with the esterification reaction.
13. A process according to claim 1 1 or claim 12, wherein said one or more functional substituents are independently selected from the group consisting of Ci-4 alkyl, Ci-4 alkoxy, nitro, cyano, halogen, fluoro-Ci-4 alkyl and fluoro-Ci-4 alkoxy.
14. A zwitterionic catalyst containing an ammonium cation and a sulfonate anion and including a structural moiety represented by the formula 1
Figure imgf000042_0001
1
wherein:
- Ri and R'i are independently selected from the group consisting of hydrogen, Ci-4 alkyl, and aryl optionally substituted with one, two or more Ci-4 alkyl substituents;
- R4 is independently hydrogen or CMO alkyl;
- p is 0 to 8;
- L represents a direct bond, a bivalent radical of the formula
Figure imgf000042_0002
R2 wherein - R2 is independently hydrogen or CMO alkyl;
- m is 0 to 4; n is 0 or 1 ;
- Ar represents an aryl optionally substituted with one, two or more substituents selected from the group consisting of hydrogen, Ci-4 alkyl, aryl, benzyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, , aryloxy, Ci-4 alkylthio, arylthio and fluoro-Ci-4 alkoxy; or
- L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring;
provided that; - when the sum of m, n and p is 0, then at least one of Ri and R'i does not represent hydrogen;
- when the sum of m and p is 0, n is 1 , and Ar represents phenyl, then at least one of Ri and R'i does not represent hydrogen, and then the ammonium cation group and the sulfonate anion group are present in ortho position of one another; and
- when L represents the bivalent radical of formula (a1 ), and Ar represents napthyl, then the ammonium cation group and the sulfonate anion group are at positions 1 and 8 of the naphtyl residue.
15. A zwitterionic catalyst according to claim 14; wherein L taken together with Ri and the N-atom to which they are attached form an optionally substituted heteroaromatic ring; structurally represented by formula 2
Figure imgf000043_0001
2
wherein:
- Het designates a heteroaromatic ring structure containing one to four nitrogen atoms and a total of 5 to 17 ring atoms,
- each R5 is independently selected from the group consisting of hydrogen, C-1 -4 alkyl, halogen, fluoro-Ci-4 alkyl, nitro, hydroxyl, Ci-4 alkoxy, Ci-4 alkylthio and fluoro-Ci-4 alkoxy,
- each R is independently selected from the group consisting of hydrogen and Ci-io alkyl, and
- p is 0 to 8; in particular p is 0 to 4.
16. A zwitterionic catalyst according to claim 15; wherein;
- Het designates a heteroaromatic ring structure containing one nitrogen atom; more in particular Het designates a heterocyclic iminium cation; even more in particular Het designates a pyridinium ring;
- R5 is hydrogen;
- R is hydrogen, and
- p is 0 to 8; in particular p is 0 to 4.
17. A zwitterionic catalyst according to any one of claims 14 to 16, and selected from the group consisting of;
- 5-methyl-2-(p-tolylamino)benzenesulfonic acid;
- o-sulfanilic acid;
- 4-(phenylamino)benzenesulfonic acid;
- 4-(dimethylamino)benzenesulfonic acid;
- 2-aminonaphthalene-1 -sulfonic acid;
- 4-(ethylamino)benzenesulfonic acid;
- 2-amino-4-methylbenzenesulfonic acid;
- 2-(phenylamino)ethanesulfonic acid;
- 8-aminonaphthalene-1 -sulfonic acid;
- 8-(phenylamino)naphthalene-1 -sulfonic acid;
- (2-(phenylamino)phenyl)methanesulfonic acid;
- pyridine-2-sulfonic acid;
- 3-Pyridinesulfonic acid;
- 4-Pyridineethanesulfonic acid; and
- Quinoline-8-sulfonic acid;
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2868650A1 (en) 2013-10-30 2015-05-06 Agfa Graphics Nv Synthesis of acetal compounds using zwitterionic catalysts
CN108546232A (en) * 2018-05-22 2018-09-18 湖北汇达科技发展有限公司 A kind of monosubstituted or disubstituted benzene formic ether compounds preparation methods
CN112705268A (en) * 2019-10-25 2021-04-27 香港中文大学 Zwitterionic-ruthenium complexes for catalysing aerobic oxidation reactions
CN114950552A (en) * 2022-06-23 2022-08-30 江西大地制药有限责任公司 Novel sulphonamido silicone oil ionic liquid acid catalyst
CN116199603A (en) * 2022-12-27 2023-06-02 沈阳化工研究院有限公司 Method for synthesizing N, N-diethyl-4-aminobenzenesulfonic acid by adopting continuous flow

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040204409A1 (en) * 2003-04-10 2004-10-14 Kazuo Ando Bicyclic compounds as NR2B receptor antagonists
CN1762974A (en) 2005-09-30 2006-04-26 清华大学 Tributyl citrate preparation method using ion liquid catalysis

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040204409A1 (en) * 2003-04-10 2004-10-14 Kazuo Ando Bicyclic compounds as NR2B receptor antagonists
CN1762974A (en) 2005-09-30 2006-04-26 清华大学 Tributyl citrate preparation method using ion liquid catalysis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LUCENA I L ET AL: "Oleic acid esterification with ethanol under continuous water removal conditions", FUEL, IPC SCIENCE AND TECHNOLOGY PRESS, GUILDFORD, GB, vol. 90, no. 2, 1 February 2011 (2011-02-01), pages 902 - 904, XP027511061, ISSN: 0016-2361, [retrieved on 20101120], DOI: 10.1016/J.FUEL.2010.10.022 *
M. D'OCA ET AL.: "Sulfamic acid: An efficient acid catalyst for esterification of FFA", FUEL, vol. 97, 29 February 2012 (2012-02-29), pages 884 - 886, XP002683263 *

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* Cited by examiner, † Cited by third party
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WO2015062935A1 (en) * 2013-10-30 2015-05-07 Agfa Graphics Nv Synthesis of acetal compounds using zwitterionic catalysts
CN105658614A (en) * 2013-10-30 2016-06-08 爱克发印艺公司 Synthesis of acetal compounds using zwitterionic catalysts
CN105658614B (en) * 2013-10-30 2018-03-06 爱克发有限公司 Acetal compound is synthesized using amphoteric catalyst
US9982072B2 (en) 2013-10-30 2018-05-29 Agfa Nv Synthesis of acetal compounds
CN108546232A (en) * 2018-05-22 2018-09-18 湖北汇达科技发展有限公司 A kind of monosubstituted or disubstituted benzene formic ether compounds preparation methods
CN108546232B (en) * 2018-05-22 2020-10-16 湖北汇达科技发展有限公司 Preparation method of mono-substituted or di-substituted benzoate compound
CN112705268A (en) * 2019-10-25 2021-04-27 香港中文大学 Zwitterionic-ruthenium complexes for catalysing aerobic oxidation reactions
CN112705268B (en) * 2019-10-25 2024-02-13 香港中文大学 Zwitterionic-ruthenium complexes for catalyzing aerobic oxidation reactions
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