US008865921B2
`
`(12) United States Patent
`Mu?oz De Diego et al.
`
`(10) Patent N0.:
`(45) Date of Patent:
`
`US 8,865,921 B2
`Oct. 21, 2014
`
`(54) METHOD FOR THE PREPARATION OF
`2,5-FURANDICARBOXYLIC ACID AND FOR
`THE PREPARATION OF THE DIALKYL
`ESTER OF 2,5-FURANDICARBOXYLIC ACID
`
`(75) Inventors: Cesar Mu?oz De Diego, Amsterdam
`(NL); Matheus Adrianus Dam,
`Amsterdam (NL); Gerardus Johannes
`Maria Gruter, Amsterdam (NL)
`
`(73) Assignee: Furanix Technologies B.V.,Amsterdam
`(NL)
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 185 days.
`
`(21) App1.No.:
`
`13/497,690
`
`(22) PCT Filed:
`
`Oct. 6, 2010
`
`(86) PCT No.:
`§ 371 (0X1),
`(2), (4) Date:
`
`PCT/NL2010/050654
`
`Jul. 9, 2012
`
`(87) PCT Pub. No.: WO2011/043661
`
`PCT Pub. Date: Apr. 14, 2011
`
`(65)
`
`Prior Publication Data
`
`US 2012/0271060 A1
`
`Oct. 25, 2012
`
`Related US. Application Data
`
`(60) Provisional application No. 61/249,395, ?led on Oct.
`7, 2009.
`
`(30)
`
`Foreign Application Priority Data
`
`Oct. 7, 2009 (NL) .................................... .. 2003606
`
`(51) Int. Cl.
`C07D 307/68
`(52) US. Cl.
`
`(2006.01)
`
`CPC . . . . .
`
`. . . .. C07D 307/68 (2013.01)
`
`USPC ........................................................ .. 549/485
`(58) Field of Classi?cation Search
`CPC ................................................... .. C07D 307/68
`
`USPC ........................................................ .. 549/485
`See application ?le for complete search history.
`
`(56)
`
`References Cited
`
`U.S. PATENT DOCUMENTS
`
`2/1953 Bruno
`2,628,249 A
`3/1954 Kuhn et al.
`2,673,860 A
`4,977,283 A 12/1990 Leupold et al.
`2009/0156841 A1
`6/2009 Sanborn et al.
`
`FOREIGN PATENT DOCUMENTS
`
`3/1990
`0356703 A2
`EP
`10/1947
`621971
`GB
`6/2007
`2009001519
`JP
`10/2009
`2009242312
`JP
`6/1976
`636233
`RU
`01/72732 A2 10/2001
`WO
`2006/063220 A2
`6/2006
`WO
`2007/104515 A1
`9/2007
`WO
`2008/054804 A2
`5/2008
`WO
`2009/030512 A2
`3/2009
`WO
`2009/076627 A2
`6/2009
`WO
`W0 WO 2009/076627 A2
`6/2009
`WO
`2010/132740 A2 11/2010
`
`OTHER PUBLICATIONS
`
`Boisen et al., “Process integration for the conversion of glucose to
`2,5-furandicarb0xylic acid”, Chemical Engineering Research and
`Design, Part A, Institution of Chemical Engineers, v01. 87, N0. 9, pp.
`1318-1327, 2009.
`“The Electrochemical Oxidation of
`al.,
`Grabowski et
`S-Hydroxymethyfurfural With the Nickel Oxide/Hydroxide Elec
`trode”, Electrochimica ACTA, v01. 36, N0. 13, p. 1995, 1991.
`Haworth et al., “The Conversion of Sucrose into Furan Compounds.
`Part II. Some 2: 5-disubstituted tetrahydrofurans and their products
`ofring scission”, Journal of the Chemical Society, pp. 1-4, 1945.
`Partenheimer et al., “Synthesis of 2,5-Dif0rmy1furan and Furan-2,5
`Dicarboxylic
`Acid
`by
`Catalytic
`Air-Oxidation
`of
`5-Hydr0xymethylfurfural. Unexpectedly Selective Aerobic Oxida
`tion of Benzyl Alcohol t0 Benzaldehyde With Metal/Bromide Cata
`lysts”, Adv. Synth. Catal, vol. 343, N0. 1, pp. 102-111, 2001.
`Tong et al., “Biomass into chemicals: Conversion of sugars t0 furan
`derivatives by catalytic processes”, Applied Catalysis A: General,
`vol. 385, No. 1-2, pp. 1-13, 2010.
`English translation of a Chinese Of?ce Action dated Dec. 4, 2013 for
`a counterpart foreign application.
`English translation of communication dated Dec. 4, 2013 from a
`counterpart foreign (Chinese) application.
`
`Primary Examiner * Tao?q A Solola
`(74) Attorney, Agent, or Firm * John S. Sopko; Hoffman &
`Baron, LLP
`
`(57)
`
`ABSTRACT
`
`A method for the preparation of 2,5-furan dicarboxylic acid
`includes the step of contacting a feed comprising a compound
`selected from the group consisting of 5-hydroxymethylfur
`fural (“HMF”), an ester of 5-hydroxymethyl-?1rfural, 5-me
`thylfuriural, 5-(chloromethyl)?1r?1ral, 5-methylfuroic acid,
`5-(chloromethyl)furoic acid, 2,5-dimethylfuran and a mix
`ture of two or more of these compounds With an oxidant in the
`presence of an oxidation catalyst at a temperature higher than
`140° C.
`
`10 Claims, No Drawings
`
`Petitioners' Exhibit 1001, Page 1 of 6
`
`

`
`US 8,865,921 B2
`
`1
`METHOD FOR THE PREPARATION OF
`2,5-FURANDICARBOXYLIC ACID AND FOR
`THE PREPARATION OF THE DIALKYL
`ESTER OF 2,5-FURANDICARBOXYLIC ACID
`
`CROSS-REFERENCE TO RELATED
`APPLICATIONS
`
`This application is the National Stage of International
`Application No. PCT/NL2010/050654, ?led Oct. 6, 2010,
`which claims the bene?t of Netherlands Application No.
`2003606, ?led Oct. 7, 2009, and U.S. Provisional Application
`No. 61/249,395, ?led Oct. 7, 2009, the contents of all of
`which are incorporated by reference herein.
`
`FIELD OF THE INVENTION
`
`The present invention relates to a method for the prepara
`tion of 2,5-furandicarboxylic acid (“FDCA”) from 5-hy
`droxymethylfurfural (“HMF”) and/or derivatives thereof.
`FDCA can be produced in particular from esters of HMF,
`such as for example 5-acetoxymethylfurfural (AMF) or a
`mixture of one or more of these compounds with HMF, such
`as for example from a mixture of AMP and HMF. The inven
`tion further relates to a process for the preparation of the
`dialkyl ester of 2,5-furandicarboxylic acid.
`
`BACKGROUND OF THE INVENTION
`
`2,5-Furandicarboxylic acid, also known as dehydromucic
`acid is a furan derivative. This organic compound was ?rst
`obtained by Fittig and Heinzelmann in 1876. The ?rst review,
`by Henry Hill was published in 1901 (Am. Chem. Journ. 25,
`439). FDCA was more than 125 years later identi?ed by the
`US Department of Energy as one of 12 priority chemicals for
`establishing the “green” chemistry industry of the future.
`However, to date, no commercial process exists for its pro
`duction. On laboratory scale it is often synthesized from
`5-hydroxymethylfurfural (HMF), which in turn can be
`obtained from carbohydrate containing sources such as glu
`cose, fructose, sucrose and starch. From fructose and glucose
`HMF is obtained by acidic elimination of three moles of
`water.
`The derivatives of HMF are identi?ed as potential and
`versatile fuel components and precursors for the production
`of plastics. The polyester from FDCA dimethyl diester and
`ethylene glycol was ?rst reported in 1946 (GB 621,971).
`WO 01/72732 describes the oxidation of HMF to FDCA.
`The maximum FDCA yield reported is 59%, obtained at 105°
`C. The oxidation of HMF in an aqueous medium with oxygen
`using a catalyst from the Pt-group is described in U.S. Pat.
`No. 4,977,283. Taaming et al. described the oxidation of
`HMF over gold based catalysts (ChemSusChem, 2008, 1,
`1-4).
`Partenheimer et al (Adv. Synth. Catal. 2001, 343, pp 102
`11) describe the synthesis of 2,5-furandicarboxylic acid by
`catalytic air-oxidation of 5-hydroxymethylfurfural with
`metal/bromide catalysts such as Co/Mn/Br in acetic acid at
`temperatures ranging from 50 to 125° C. With the Co/Mn/Br
`catalyst the highest FDCA yield obtained is 35.2% (Table 3,
`experiment 4). On page 103 of the same paper, under the
`header “products formed” it is stated: “A side reaction is the
`esteri?cation of the alcohols to form the more oxidatively
`stable acetate .
`.
`. ” As apparently 5-hydroxymethylfurfural
`reacts with acetic acid a loss of the starting material takes
`place. Further, in the reaction scheme given in FIG. 1 on page
`103, it is indicated that 5-(acetoxymethyl)furfural is an end
`
`2
`point. There is no further reaction of this compound indicated
`to FDCA (in contrast to the ester of the intermediate product
`5-(acetoxymethyl)furan-2-carboxylic acid). In other words,
`the 5-(acetoxymethyl)furfural (AMF) formed through reac
`tion of HMF with acetic acid solvent, is not oxidized to FDCA
`and its formation leads therefore to yield loss.
`This result was con?rmed in U.S. 2009/0156841.Although
`the intention of the process according to U.S. 2009/0156841
`was to obtain FDCA, the product isolated and erroneously
`characterized as being FDCA was in fact the starting material
`acetoxymethyl furfural (AMF). Under the low temperature
`conditions deployed (100° C.), AMF is quite stable, as was
`already reported by Partenheimer (see above).
`In U.S. 2009/0156841 a 1H NMR spectrum is shown in
`FIG. 8 and suggested that it is the spectrum of the product that
`was identi?ed as FDCA. However, this is not the case. The 1H
`NMR spectrum of the product shown in FIG. 8 is the same as
`that in FIG. 6 and represents the starting material AMP. The
`1H NMR spectrum of FDCA shows a singlet at a shift of
`about 7.26 ppm. Moreover, the product is described as a tan
`solid. In the experience of the present inventors, AMF is a tan
`solid, while FDCA is a white solid. It would seem that no
`FDCA was obtained in the experiments according to U.S.
`2009/0156841.
`The experiments executed under the conditions of U.S.
`2009/0156841 were repeated. These comparative experi
`ments con?rm the low reactivity of AMP under conditions
`given in U.S. 2009/0156841. Thus, a person skilled in the art
`would therefore have concluded that FDCA cannot be
`obtained in interesting yields from AMF using the conditions
`that are reported in U.S. 2009/0156841, i.e., using a Co/Mn/
`Br catalyst in acetic acid at between 85 and 110° C. within a
`time frame of from 100 and 150 minutes. In Example 7 of
`U.S. 2009/0156841, slightly more than 50% of the starting
`material was the only product isolated from the reaction.
`
`SUMMARY OF THE INVENTION
`
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`The present inventors have now surprisingly found that
`when using an oxidation catalyst, e.g., based on both cobalt
`and manganese and containing a bromide, at temperatures
`higher than 140° C., derivatives of HMF, and in particular
`esters of HMF optionally in combination with HMF, such as
`for example 5-(acetoxymethyl)furfural (AMF) can be oxi
`dized to FDCA in high yields.
`
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`DETAILED DESCRIPTION OF THE INVENTION
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`Thus, in a ?rst aspect the invention provides a method for
`the preparation of 2,5-furan dicarboxylic acid comprising the
`step of contacting a feed comprising a compound selected
`from the group consisting of 5-hydroxymethylfurfural
`(“HMF”), an ester of 5-hydroxymethyl-furfural, 5-methyl
`furfural, 5-(chloromethyl)furfural, 5-methylfuroic acid,
`5-(chloromethyl)furoic acid, 2,5-dimethylfuran and a mix
`ture of two or more of these compounds with an oxidant in the
`presence of an oxidation catalyst at a temperature higher than
`140° C. The feed may optionally comprise 5-hydroxymeth
`ylfurfural as a further compound.
`The invention described hereinafter may use any of the
`compounds described above in the feed. A preferred ester of
`HMF contains an ester moiety of an alkyl carboxylic acid
`wherein the alkyl group contains up to 6 carbon atoms, pref
`erably from 1 to 5 carbon atoms, i.e. methyl, ethyl, propyl,
`isopropyl, butyl, 2-butyl, tert-butyl, pentyl, 2-pentyl, neopen
`tyl and 3-pentyl. Particularly preferred are alkyl groups with
`1 to 4 carbon atoms. There is a preference for methyl, giving
`
`Petitioners' Exhibit 1001, Page 2 of 6
`
`

`
`US 8,865,921 B2
`
`3
`(5-acetoxymethyl)furfural. Hence, 5-acetoxymethylfurfural
`is the preferred feedstock, by itself or in combination with
`HMF.
`In another aspect of the invention, we have also investi
`gated the oxidation of other furan-based substrates under the
`process conditions according to the current invention. We
`have been able to convert 5-(chloromethyl)?1rfural, 5-(chlo
`romethyl)furoic acid, 5-methylfurfural, 5-methylfuroic acid
`and 2,5-dimethylfuran all to FDCA in very interesting yields.
`In WO 2007/ 104515 and WO 2009/030512, the synthesis
`of esters of HMF such as 5-acetoxymethylfurfural (AMF)
`from biomass sources is described. Given the higher stability
`of the HMF esters than HMF and hence improved production
`pathways and given the fact that upon oxidation in acetic acid
`the acetoxy functionality that was obtained from acetic acid is
`now liberated as acetic acid and given the green reputation of
`these esters, they were considered by the present inventors as
`interesting starting point in the preparation of furan-based
`monomers that could be used for the production of furandi
`carboxylic acid-based polyesters, for instance as an alterna
`tive for PET or FDCA-based polyamids (nylons). The most
`important conventional, oil-based, polyester monomer to
`produce PET is Puri?ed Terephthalic acid (PTA) and its
`dialkyl ester DiMethyl Terephthalate (DMT).
`AMF canbe obtained from biomass sources as described in
`WO 2007/ 104515 and WO 2009/030512. Depending on the
`process conditions the product obtained in accordance with
`the process of these references may also contain HMF.
`FDCA, the product of the reaction can be used in the
`preparation of a polyester, by reaction of FDCA or its dialkyl
`ester with a suitable diol. Such polyester preparations are
`preferably performed by transesteri?cation, whereby the di
`methyl ester or di-ethyl ester of FDCA is used and wherein
`the methyl or ethyl groups are exchanged in the form of a
`volatile alcohol during the transesteri?cation with the diol.
`The oxidation catalyst can be selected from a variety of
`oxidation catalysts, but is preferably a catalyst based on both
`cobalt and manganese and suitably containing a source of
`bromine, preferably a bromide.
`The bromine source can be any compound that produces
`bromide ions in the reaction mixture. These compounds
`include hydrogen bromide, sodium bromide, elemental bro
`mine, benzyl bromide and tetrabromoethane. Also other bro
`mine salts, such as an alkali or alkaline earth metal bromide or
`another metal bromide such as ZnBr2 can be used. There is a
`preference for hydrobromic acid or sodium bromide. The
`amount of bromine mentioned in here relates to the amount
`measured as Br relative to cobalt.
`Suitable metal bromide catalysts employed in all of the
`processes of this invention comprise a cobalt compound and
`a manganese compound and a bromine-containing com
`pound. Preferably these compounds are soluble in the reac
`tion mixture.
`Preferably, the catalyst comprises both Co and Mn. The
`metal and bromide catalyst contains, in addition to bromide,
`Co and Mn and optionally may contain one or more additional
`metals, in particular Zr and/or Ce. Alternative and suitable
`catalysts are described in W. Partenheimer, Catalysis Today
`23 (2), 69-158 (1995) in particular on pages 89-99, included
`herein by reference.
`Each of the metal components can be provided in any of
`their known ionic forms. Preferably the metal or metals are in
`a form that is soluble in the reaction solvent. Examples of
`suitable counterions for cobalt and manganese include, but
`are not limited to, carbonate, acetate, acetate tetrahydrate and
`halide, with bromide being the preferred halide.
`
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`As described in Partenheimer, ibid, pages 86-88, suitable
`solvents for use in the processes of the present invention,
`described above, preferably have at least one component that
`contains a monocarboxylic acid functional group. The sol
`vent may also function as one of the reagents. The processes
`may be run in a solvent or solvent mixture that does not
`contain an acid group. In that case, preferably one of the
`reagents does contain a monocarboxylic acid functional
`group. Suitable solvents can also be aromatic acids such as
`benzoic acid and derivatives thereof. A preferred solvent is an
`aliphatic C2-C6 monocarboxylic acid, such as but not limited
`to acetic acid, propionic acid, n-butyric acid, isobutyric acid,
`n-valeric acid, trimethylacetic acid, and caproic acid and mix
`tures thereof. Said mixtures may also include benzene, aceto
`nitrile, heptane, acetic anhydride, chlorobenzene, o-dichlo
`robenzene, and water. The most preferred solvent is acetic
`acid (“AcOH”).
`The oxidant in the processes of the present invention is
`preferably an oxygen-containing gas or gas mixture, such as,
`but not limited to air and oxygen-enriched air. Oxygen by
`itself is also a preferred oxidant.
`The processes of the instant invention described above can
`be conducted in a batch, semi-continuous or continuous
`mode. Especially for the manufacture of FDCA, operation in
`the batch mode with increasing temperature at speci?c times,
`increasing pressure at speci?c times, variation of the catalyst
`concentration at the beginning of the reaction, and variation
`of the catalyst composition during the reaction is desirable.
`For example, variation of the catalyst composition during the
`reaction can be accomplished by addition of cobalt and/or
`manganese and/ or Zirconium, and/ or cerium, and/ or bromide
`at speci?ed times.
`The pressure in a commercial oxidation process may vary
`within wide ranges. When a diluent is present, and in particu
`lar with acetic acid as diluent, the temperature and the pres
`sure in such a process are not independent. The pressure is
`determined by the solvent (e.g., acetic acid) pressure at a
`certain temperature. The pressure of the reaction mixture is
`preferably selected such that the solvent is mainly in the
`liquid phase. In practice this means that pressures between 5
`and 100 bar can be used with a preference for pressures
`between 10 and 80 bar. In case the oxidant is an oxygen
`containing gas, such as air, the gas can be continuously fed to
`and removed from the reactor, or the gas can be supplied all at
`the start of the reaction. In the latter case, the pressure of the
`system will depend on the headspace volume and the amount
`of gas required to convert the starting material. It is clear that
`in the latter case, the pressure of the system may be signi?
`cantly higher than the pressure in a process wherein an oxy
`gen containing gas is continuously fed and removed. In the
`case of continuously feeding and removing the oxidant gas to
`and from the reactor, the oxygen partial pressure will suitably
`be between 1 and 30 bar or more preferably between 1 and 10
`bar.
`The temperature of the reaction mixture is at least 140° C.,
`preferably from 140 and 200° C., most preferably between
`160 and 190° C. Temperatures higher than 180° C. may lead
`to decarboxylation and to other degradation products. Good
`results to FDCA have been achieved at a temperature of about
`180° C.
`Molar ratios of cobalt to manganese (Co/Mn) are typically
`1/1000-100/ 1, preferably 1/100-10/1 and more preferably
`1/10-4/1 .
`Molar ratios of bromine to metals (e.g. Br/(Co+Mn)) are
`typically 0.001-5.00, preferably 0.01-2.00 and more prefer
`ably 0.1-0.9.
`
`Petitioners' Exhibit 1001, Page 3 of 6
`
`

`
`US 8,865,921 B2
`
`5
`Catalyst concentration (C0+Mn) is typically from 0.1 to 10
`mol %, relative to the substrate, with a preference for concen
`trations from 2 to 6 mol %. Good results were obtained in
`general with catalyst concentrations of around 4 mol %.
`The starting materials for the production of FDCA may
`originate from a carbohydrate source as described above.
`Examples of such disclosures are WO 2007/ 104515 and WO
`2009/030512. Accordingly, the invention also provides a
`method for the preparation of 2,5-furandicarboxylic acid
`wherein a carbohydrate source is converted in the presence of
`an alkyl carboxylic acid into products comprising an HMF
`ester and optionally 5-hydroxymethyl furfural, from which is
`isolated a feed comprising the ester of HMF and optionally
`5-hydroxymethyl furfural, and which method further com
`prises the subsequent step of contacting the feed with an
`oxidant in the presence of an oxidation catalyst, in particular
`a cobalt and manganese and bromide-containing catalyst,
`under appropriate reaction conditions, in particular at tem
`peratures higher than 140° C.
`In another aspect, the FDCA obtained according to the
`process of the present invention can be transformed using
`common esteri?cation reactions to a diester by contacting the
`starting material under appropriate conditions with the rel
`evant alcohol. Thus, in one aspect, the invention also relates to
`the use of FDCA obtained according to the process of the
`current invention in the preparation of a dialkylester of 2,5
`dicarboxylic acid by reaction of the FDCA with a C 1 -C5 alkyl
`alcohol, preferably methanol to prepare the dimethyl ester of
`FDCA.
`Accordingly, the present invention also provides a process
`for the preparation of a dialkyl ester of 2,5 ,-furan dicarboxylic
`acid, comprising the step of contacting a feed comprising a
`compound selected from the group consisting of 5-hy
`droxymethylfurfural (“HMF”), an ester of 5 -hydroxymethyl
`furfural, 5-methylfurfural, 5-(chloromethyl)fur?1ral, 5-meth
`ylfuroic
`acid,
`5-(chloromethyl)furoic
`acid,
`2,5
`dimethylfuran and a mixture of two or more of these
`compounds with an oxidant in the presence of an oxidation
`catalyst at a temperature higher than 140° C., and esterifying
`the thus obtained product. Preferably, the product is esteri?ed
`with an alkyl alcohol, suitably having 1 to 5 carbon atoms.
`The esteri?cation of 2,5-furan dicarboxylic acid is known.
`As a speci?c example for the manufacture of these esters,
`reference is made to Us. Pat. No. 2,673,860 wherein the
`diester is obtained by transesteri?cation of another dicar
`boxylic acid ester in the presence of sulphuric acid. A more
`general description for the esteri?cation of dicarboxylic acids
`is presented in Us. Pat. No. 2,628,249. Accordingly, the
`invention provides a process for the preparation of a dialkyl
`ester of 2,5,-furan dicarboxylic acid, comprising the step of
`contacting a feed comprising a compound selected from the
`group consisting of 5-hydroxymethylfurfural (“HMF”), an
`ester of 5-hydroxymethyl-furfural,
`5-methylfurfural,
`5-(chloromethyl)?1rfural, 5-methylfuroic acid, 5-(chlorom
`ethyl)furoic acid, 2,5-dimethylfuran and a mixture of two or
`more of these compounds with an oxidant in the presence of
`an oxidation catalyst at a temperature higher than 140° C., and
`esterifying the thus obtained product.
`In a further aspect of the invention, the di-methylester can
`be used in the preparation of polyester polymers by reaction
`with a diol. Reacting the di-methylester with a diol will result
`in the formation of methanol that quickly vaporises. In 1946
`the polymerization of FDCA dimethyl ester with ethylene
`glycol was described as a ?rst example of such a polymeriza
`tion in GB 621,971.
`Indeed, polyesters are generally made by a combined
`esteri?cation/polycondenzation reaction between monomer
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`units of a diol (e. g., ethylene glycol (EG)) and a dicarboxylic
`acid. Additives such as catalysts and stabilizers may be added
`to facilitate the process and stabilize the polyester towards
`degradation.
`
`EXAMPLES
`
`Experiments were carried out in parallel 8 ml magnetically
`stirred stainless steel batch reactors. The reactors are grouped
`in blocks containing 12 batch reactors. The standard proce
`dure for all the reactions was as follows:
`0.5 ml of starting material stock solution in acetic acid
`(0.78 mmol/ml) were added into a reactor lined with a Te?on
`insert. To the reactor 1 ml of a catalyst stock solution in acetic
`acid was subsequently added. In a typical experiment, a cata
`lyst composition Co/Mn/Br with a relative 1-x-y ratio, the
`concentration of Co(OAc)2* 4HZO was varied. As a Mn
`source, Mn(OAc)2*4HZO was used and as a bromine source
`NaBr was used. The reactors were closed with a rubber sep
`tum, after which the reactors were sealed and pressurized to
`the desired air pressure, ranging from 20-60 bars. After pres
`surization, the block with 12 reactors was placed in the test
`unit which was preheated at the desired temperature, ranging
`from 100 to 220° C. After the desired reaction time, ranging
`from 0.5 hr to 24 hrs, the block is placed into an ice bath for
`20 minutes. When the block had cooled down, it was depres
`surized. After opening, HPLC samples were prepared. First 5
`ml of a saccharine solution in DMSO (11.04 mg/ml) was
`added to each reactor and the mixture was stirred for 5 min
`utes. Then 10 pl of this mixture was diluted to 1000 pl with
`water in a HPLC vial. The samples were analyzed using
`HPLC.
`
`Example 1
`
`Example 1 shows the selectivity of FDCA in the oxidation
`of HMF, of a HMF/AMF 3/2 mixture, of a HMF/AMF 2/3
`mixture and of AME, respectively, with 2.7 mol % Co catalyst
`(relative to substrate), and Co/Mn molar ratio of 1/ 1, so that
`the catalyst concentration (C0+Mn) amounted to 5.4 mol %.
`The Br/(Co+Mn) molar ratio was 1.0; 0.7; 0.4 and 0.1 at 0.26
`M substrate concentration in acetic acid at 180° C. for 1 hr
`with 20 bar air. The amount of oxygen was 2.69 mol oxygen
`per mol substrate. Under these conditions, higher Br amounts
`give higher yields but when Br/ (Co +Mn)>1 , corrosion will be
`a problem on commercial scale. HMF gives slightly higher
`yields than AMF at one hour reaction time. The results of
`these experiments are given in Table 1.
`
`Example 2
`
`Example 2 shows the selectivity to FDCA for the AME
`oxidation of Example 1, together with the comparative
`examples based on the experimental conditions described in
`Us. 2009/0156841. In those comparative experiments (2a
`and 2b) 10 wt/wt % AMF in acetic acid was oxidized with
`1.75 and 2.65 mol % Co catalyst and a ?xed Br/(Co+Mn)
`molar ratio of 1.0 and a Co/Mn molar ratio of 1.0 at 100° C.
`and 30 bar for 2 hours. The amount of oxygen was 2.88 mol
`oxygen per mol substrate. Under these conditions, the yield of
`FDCA was lower than the result suggested in Us. 2009/
`0156841 and also lower than the results obtained at higher
`temperature. The results of these experiments are given in
`Table 2.
`
`Example 3
`
`Example 3 shows the yield of FDCA in the oxidation of
`5-methylfurfural (5MP) and 2,5-dimethylfurfural (DMF) at
`
`Petitioners' Exhibit 1001, Page 4 of 6
`
`

`
`US 8,865,921 B2
`
`8
`7
`compounds with an oxygen-containing gas, in the presence of
`180° C. with 2.7 mol % Co catalyst (relative to substrate), and
`an oxidation catalyst comprising both Co and Mn, and further
`Co/Mn ratio of 1/ 1, so that the catalyst concentration (Co+
`Mn) amounted to 5.4 mol %. The Br/(Co+Mn) molar ratio
`a source of bromine, at a temperature between 140° C. and
`was 1.0, 0.7, 0.4 and 0.1. The substrate concentration was
`200° C. at an oxygen partial pressure of 1 to 10 bar, wherein
`0.26 M in acetic acid. The reaction temperature was at 180° C. 5 a solvent or solvent mixture comprising acetic acid or acetic
`and the reaction was conducted with 50 bars air. The amount
`acid and water mixtures is present.
`of oxygen was 6.7 mol oxygen per mol substrate. Under these
`2. The method according to claim 1, wherein the feed
`conditions, higher Br amounts give higher yields but when
`comprises a compound selected from the group consisting of
`Br/(Co+Mn)>1, corrosion will be a problem on commercial
`5-hydroxymethylfurfural (“HMF”), esters of HMF and a
`scale. Reactions with 5-MF give higher yields than reactions 10 mixture thereof.
`3. The method according to claim 1, wherein the oxidation
`with DMF. The results of these experiments are also given in
`catalyst comprises at least one additional metal.
`Table 3.
`
`TABLE 1
`
`Experiment
`
`Substrate HMF/AMF
`molar ratio
`
`Substrate
`concentration Conversion s FDCA
`
`No.
`
`HMF
`
`AMF Br/(Co + Mn)
`
`[wt %]
`
`[%]
`
`[%]
`
`1a
`1b
`10
`1d
`1e
`1f
`1g
`1h
`1i
`lj
`1k
`11
`lrn
`1n
`10
`1p
`
`1
`3
`2
`0
`1
`3
`2
`0
`1
`3
`2
`0
`1
`3
`2
`0
`
`0
`2
`3
`1
`0
`2
`3
`1
`0
`2
`3
`1
`0
`2
`3
`1
`
`1
`1
`1
`1
`0.7
`0.7
`0.7
`0.7
`0.4
`0.4
`0.4
`0.4
`0.1
`0.1
`0.1
`0.1
`
`3.3
`3.8
`4.0
`4.4
`3.3
`3.8
`4.0
`4.4
`3.3
`3.8
`4.0
`4.4
`3.3
`3.8
`4.0
`4.4
`
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`
`76.66
`71.19
`77.66
`64.82
`78.08
`66.96
`75.14
`60.64
`73.27
`65.67
`73.21
`57.36
`67.92
`60.92
`69.64
`46.85
`
`TABLE 2
`
`Catalyst
`Reaction concentration
`Experiment Temp time
`[(Co + Mn)
`No.
`[° C.] [Hours]
`rnol %]
`
`Substrate
`Br/
`(Co + OZ/Subs concentration Conversion s FDCA
`Mn/Co Mn) [mol/mol]
`[wt %]
`[%]
`[%]
`
`1d
`1h
`11
`1p
`2a
`2b
`
`180
`180
`180
`180
`100
`100
`
`1
`1
`1
`1
`2
`2
`
`5.4
`5.4
`5.4
`5.4
`3.5
`5.3
`
`1
`1
`1
`1
`1
`1
`
`1
`0.7
`0.4
`0.1
`1
`1
`
`2.69
`2.69
`2.69
`2.69
`2.88
`2.88
`
`4.4
`4.4
`4.4
`4.4
`10.0
`10.0
`
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`
`64.82
`60.64
`57.36
`46.85
`23.48
`29.05
`
`TABLE 3
`
`Experiment
`No.
`
`Substrate
`Reaction
`OZ/Subs concentration Conversion s FDCA
`Br/
`time
`Substrate [Hours] (Co + Mn) [mol/mol]
`[wt %]
`[%]
`[%]
`
`3a
`3b
`30
`3d
`3e
`3f
`
`5—MF
`5—MF
`DMF
`DMF
`DMF
`DMF
`
`1
`1
`1
`1
`1
`1
`
`1
`0.7
`1
`0.7
`0.4
`0.1
`
`6.7
`6.7
`6.7
`6.7
`6.7
`6.7
`
`2.9
`2.9
`2.5
`2.5
`2.5
`2.5
`
`100.00
`100.00
`100.00
`100.00
`100.00
`100.00
`
`42.62
`39.94
`16.17
`14.09
`11.30
`7.19
`
`The invention claimed is:
`1. A method for the preparation of 2,5-furan dicarboxylic
`acid comprising the step of contacting a feed comprising a
`compound selected from the group consisting of 5-hy
`droxymethylfurfural (“HMF”), an ester of 5 -hydroxymethyl
`furfural, 5-methylfurfural, 5-(chloromethyl)fur?.1ral, 5-meth
`ylfuroic
`acid,
`5-(chloromethyl)furoic
`acid,
`2,5
`dimethylfuran and a mixture of two or more of these
`
`60
`
`65
`
`4. The method according to claim 3, wherein the additional
`metal is Zr and/ or Ce.
`5. The method according to claim 1, wherein the tempera
`ture is between 160 and 190° C.
`6. The method according to claim 1, wherein the feed
`comprises an ester of HMF having an ester moiety of an alkyl
`carboxylic acid wherein the alkyl group has up to 6 carbon
`atoms.
`
`Petitioners' Exhibit 1001, Page 5 of 6
`
`

`
`US 8,865,921 B2
`
`10
`
`7. A process for the preparation of a dialkyl ester of 2,5,
`furan dicarboxylic acid, comprising the step of contacting a
`feed comprising a compound selected from the group con
`sisting of 5-hydroxymethylfurfural (“HMF”), an ester of
`5-hydroxymethyl-furiural, 5-methylfurfural, 5-(chlorom
`ethyl)furfural, 5-methylfuroic acid, 5-(chloromethyl)furoic
`acid, 2,5 -dimethylfuran and a mixture of two or more of these
`compounds With an oxygen-containing gas in the presence of
`an oxidation catalyst comprising both Co and Mn, and further
`a source of bromine, at a temperature between 140° C. and
`200° C. at an oxygen partial pressure of 1 to 10 bar, Wherein
`a solvent or solvent mixture comprising acetic acid or acetic
`acid and water mixtures is present, and esterifying the thus
`obtained product.
`8. The process according to claim 7, Wherein the product is
`esteri?ed With a C1-C5 alkyl alcohol.
`9. The process according to claim 8, Wherein the C1-C5
`alkyl alcohol is methanol and the dialkyl ester is the dimethy
`lester of 2,5-furan dicarboxylic acid.
`10. A method according to claim 2, Wherein the feed com
`prises an HMF ester and optionally 5-hydroxymethyl fur
`fural, Which has been obtained by converting a carbohydrate
`source in the presence of an alkyl carboxylic acid.
`
`20
`
`*
`
`*
`
`*
`
`*
`
`*
`
`Petitioners' Exhibit 1001, Page 6 of 6