General Papers
`General Papers (cid:9)
`
`ARKIVOC 2001 (i) 17-54
`ARKIVOC 2001 (i) 17-54
`
`
`
`
`
`Synthesis, chemistry and applications of 5-hydroxymethylfurfural
`Synthesis, chemistry and applications of 5-hydroxymethylfurfural
`and its derivatives
`and its derivatives
`
`Jarosław Lewkowski
`Jaroslaw Lewkowski
`
`Department of Organic Chemistry, University of Łódź, Narutowicza 68, 90-136 Łódź, POLAND
`Department of Organic Chemistry, University of Lodz, Narutowicza 68, 90-136 Lodi, POLAND
`E-mail: JLEWKOW@krysia.uni.lodz.pl
`E-mail: JLEWKOW@krysia.uni.lodz.pl
`(received 26 Jun 05; accepted 31 Jul 01; published on the web 08 Aug 01)
`(received 26 Jun 05; accepted 31 Jul 01; published on the web 08 Aug 01)
`
`
`Contents
`Contents
`
`Introduction
`Introduction
`
`PART A. 5-HYDROXYMETHYLFURFURAL (HMF)
`PART A. 5-HYDROXYMETHYLFURFURAL (HMF)
`1. A historical outline of studies on 5-hydroxymethylfurfural (HMF)
`1. A historical outline of studies on 5-hydroxymethylfurfural (HMF)
`2. Aspects of the synthesis of HMF
`2. Aspects of the synthesis of HMF
`2.1. The mechanism of the fructose dehydration
`2.1. The mechanism of the fructose dehydration
`2.2. The kinetics of the HMF synthesis
`2.2. The kinetics of the HMF synthesis
`3. Chemical conversions of HMF
`3. Chemical conversions of HMF
`3.1. Reactions of the Hydroxymethyl Group
`3.1. Reactions of the Hydroxymethyl Group
`3.1.1. The formation of esters
`3.1.1. The formation of esters
`3.1.2. The formation of ethers
`3.1.2. The formation of ethers
`3.1.3. The formation of halides
`3.1.3. The formation of halides
`3.1.4. The oxidation
`3.1.4. The oxidation
`3.2. Reactions of the Formyl Group
`3.2. Reactions of the Formyl Group
`3.2.1. The reduction
`3.2.1. The reduction
`3.2.2. Condensation reactions
`3.2.2. Condensation reactions
`3.2.3. Oxidation reactions
`3.2.3. Oxidation reactions
`3.3. Reactions of the furan ring
`3.3. Reactions of the furan ring
`3.4. The polymerisation of HMF
`3.4. The polymerisation of HMF
`3.5. Electrochemical conversions of HMF
`3.5. Electrochemical conversions of HMF
`
`
`PART B. 2,5-FURANDICARBALDEHYDE (FDC)
`PART B. 2,5-FURANDICARBALDEHYDE (FDC)
`4. The Synthesis of 2,5-Furandicarbaldehyde (FDC)
`4. The Synthesis of 2,5-Furandicarbaldehyde (FDC)
`5. The Chemistry and Applications of 2,5-Furandicarbaldehyde (FDC)
`5. The Chemistry and Applications of 2,5-Furandicarbaldehyde (FDC)
`
`PART C. 2,5-FURANDICARBOXYLIC ACID (FDCA)
`PART C. 2,5-FURANDICARBOXYLIC ACID (FDCA)
`6. Methods for Synthesis of 2,5-Furandicarboxylic Acid (FDCA)
`6. Methods for Synthesis of 2,5-Furandicarboxylic Acid (FDCA)
`7. The Chemistry and Applications of 2,5-Furandicarboxylic Acid (FDCA)
`7. The Chemistry and Applications of 2,5-Furandicarboxylic Acid (FDCA)
`
`Conclusions
`Conclusions
`References
`References
`
`ISSN 1424-6376
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`Page 17
`Page 17 (cid:9)
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`©ARKAT USA, Inc
`©ARKAT USA, Inc
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`Petitioners' Exhibit 1005, Page 1 of 38
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`

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`General Papers
`General Papers
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`ARKIVOC 2001 (i) 17-54
`ARKIVOC 2001 (i) 17-54
`
`Introduction
`Introduction
`
`The prospect of exciting research activity in the chemistry of furfural derived compounds such as
`The prospect of exciting research activity in the chemistry of furfural derived compounds such as
`5-hydroxymethylfurfural (HMF), 2,5-furandicarbaldehyde and 2,5-furan-dicarboxylic acid
`5-hydroxymethylfurfural (HMF), 2,5-furandicarbaldehyde and 2,5-furan-dicarboxylic acid
`prompted the writing of this article. As the field of application of these compounds is really
`prompted the writing of this article. As the field of application of these compounds is really
`enormous, it is no wonder that research in this area, starting at the end of 19th century, is still
`enormous, it is no wonder that research in this area, starting at the end of 19th century, is still
`being developed. Numerous important scientific groups are carrying out studies on the synthesis,
`being developed. Numerous important scientific groups are carrying out studies on the synthesis,
`and applications of HMF and its derivatives. Notable among these are, Gaset (Toulouse),
`and applications of HMF and its derivatives. Notable among these are, Gaset (Toulouse),
`Descotes (Lyon), Lichtenthaler (Darmstadt), and Gelas (Clermont-Ferrand). Not only academic
`Descotes (Lyon), Lichtenthaler (Darmstadt), and Gelas (Clermont-Ferrand). Not only academic
`scientists are interested in this subject, the chemical industry, is represented by sugar companies
`scientists are interested in this subject, the chemical industry, is represented by sugar companies
`such as Beghin-Say, and Süddeutsche Zucker. Despite this interest, there are not many
`such as Beghin-Say, and Si ddeutsche Zucker. Despite this interest, there are not many
`comprehensive monographs or reviews covering the chemistry of HMF. Two classic reviews, by
`comprehensive monographs or reviews covering the chemistry of HMF. Two classic reviews, by
`Newth1 and by Feather and Harris,2 appeared in 1951 and 1973 respectively. Reviews by Gaset
`Newthl and by Feather and Harris,2 appeared in 1951 and 1973 respectively. Reviews by Gaset
`et al.,3 Faury et al.4 and by Kuster5 are more recent, but they are not detailed. An important
`et al.,3 Faury et al.4 and by Kuster5 are more recent, but they are not detailed. An important
`review review by Cottier and Descotes6 appeared in 1991.
`review review by Cottier and Descotes6 appeared in 1991.
`This review is written to update those above, to summarize the contributions of the last 100
`This review is written to update those above, to summarize the contributions of the last 100
`years; and to emphasize recent developments especially in electrochemistry, and on dialdehyde
`years; and to emphasize recent developments especially in electrochemistry, and on dialdehyde
`and diacid chemistry.
`and diacid chemistry.
`
`PART A. 5-HYDROXYMETHYLFURFURAL (HMF)
`PART A. 5-HYDROXYMETHYLFURFURAL (HMF)
`
`1. A historical outline of studies on 5-hydroxymethylfurfural (HMF)
`1. A historical outline of studies on 5-hydroxymethylfurfural (HMF)
`5-Hydroxymethylfurfural (HMF) 1 has been of interest since the last decade of the 19th century.
`5-Hydroxymethylfurfural (HMF) 1 has been of interest since the last decade of the 19th century.
`In 1895 Düll7 and Kiermeyer8 working independently, published a method of synthesis and
`In 1895 Di1117 and Kiermeyer8 working independently, published a method of synthesis and
`chemical reactions of the compound, which they called “oxymethylfurfurol”.
`chemical reactions of the compound, which they called "oxymethylfurfurol".
`Later on, British chemists started their conquest; Fenton,9 Gostling10 and Robinson11
`Later on, British chemists started their conquest; Fenton,9 Gostlingi° and Robinson"
`published the results of their studies on HMF. In 1919, Middendorp12 presented the full and the
`published the results of their studies on HMF. In 1919, Middendorp12 presented the full and the
`detailed study concerning the synthesis, the physical characterisation and the chemical behaviour
`detailed study concerning the synthesis, the physical characterisation and the chemical behaviour
`of HMF.
`of HMF.
`Several years later other authors published their results, as for example Reichstein13,14 and
`Several years later other authors published their results, as for example Reichstein13'14 and
`Haworth and Jones15 – especially the latter brought immense progress in the chemistry of HMF.
`Haworth and Jones15 — especially the latter brought immense progress in the chemistry of HMF.
`They worked out the modern method of its synthesis and studied the mechanism of its formation.
`They worked out the modern method of its synthesis and studied the mechanism of its formation.
`From among a great number of papers concerning the chemistry of HMF, Karashima’s article is
`From among a great number of papers concerning the chemistry of HMF, Karashima's article is
`worth mentioning.16 He worked out the method of synthesis of 5-acetoxymethylfurfural directly
`worth mentioning.16 He worked out the method of synthesis of 5-acetoxymethylfurfural directly
`from HMF and fully characterised this compound. He reported also the formation of 5-
`from HMF and fully characterised this compound. He reported also the formation of 5-
`hydroxymethylfurfurylideneacetic acid by the Perkin condensation of HMF with acetic
`hydroxymethylfurfurylideneacetic acid by the Perkin condensation of HMF with acetic
`anhydride.
`anhydride.
`Till now, over 1000 papers have been published, which is a proof for the great importance of
`Till now, over 1000 papers have been published, which is a proof for the great importance of
`this kind of compounds. It is not possible in this work to quote all of these articles, but some
`this kind of compounds. It is not possible in this work to quote all of these articles, but some
`reviews are worth mentioning. In the “Advances in Carbohydrate Chemistry” series, two articles
`reviews are worth mentioning. In the "Advances in Carbohydrate Chemistry" series, two articles
`were published, first by Newth1 in 1951, the second appeared 20 years later by Feather.2 Moye17
`were published, first by Newth1 in 1951, the second appeared 20 years later by Feather.2 Moyer
`has written a review describing methods of the preparation and industrial applications of HMF.
`has written a review describing methods of the preparation and industrial applications of HMF.
`
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`©ARKAT USA, Inc
`©ARKAT USA, Inc
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`General Papers
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`ARKIVOC 2001 (i) 17-54
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`Later, in the 80’s, two papers were published; Gaset et al3 reviewed industrial methods of the
`Later, in the 80's, two papers were published; Gaset et al3 reviewed industrial methods of the
`preparation of HMF, Faury4 dealt with newest chemical conversions of this compound.
`preparation of HMF, Faury4 dealt with newest chemical conversions of this compound.
`Recently, Kuster5 as well as Cottier and Descotes6 have summarised the last 30 years of HMF
`Recently, Kuster5 as well as Cottier and Descotes6 have summarised the last 30 years of HMF
`chemistry. As for the application of 5-hydroxymethylfurfural in the polymer chemistry, Moore
`chemistry. As for the application of 5-hydroxymethylfurfural in the polymer chemistry, Moore
`and Kelly18 and ten years later Gandini19 reviewed this problem.
`and Kelly18 and ten years later Gandini19 reviewed this problem.
`
`2. Aspects of the synthesis of HMF
`2. Aspects of the synthesis of HMF
`The synthesis of HMF is based on the triple dehydration of hexoses. Various substrates can be
`The synthesis of HMF is based on the triple dehydration of hexoses. Various substrates can be
`used: hexoses themselves, oligo- and polysaccharides as well as converted industrial wastes20.
`used: hexoses themselves, oligo- and polysaccharides as well as converted industrial wastes".
`The acid catalysed dehydration leads, apart from HMF to various side-products (Scheme 1).
`The acid catalysed dehydration leads, apart from HMF to various side-products (Scheme 1).
`Lev,liniC acid
`Formic acid
`
`[Intermediates] (cid:9)
`
`11 (cid:9)
`
`Soluble mlymers
`Insoluble hirnic acids (cid:9)
`
`I-V17 Her
`
`
`
`Scheme 1
`Scheme 1
`
`
`Looking at the Scheme 1, one could have an impression that the synthesis of HMF is very
`Looking at the Scheme 1, one could have an impression that the synthesis of HMF is very
`simple. But studies performed by a number of independent scientists demonstrated that the
`simple. But studies performed by a number of independent scientists demonstrated that the
`chemistry of the formation of HMF is very complex; it includes a series of side-reactions, which
`chemistry of the formation of HMF is very complex; it includes a series of side-reactions, which
`influence strongly on the efficiency of the process. The decomposition to levulinic acid and the
`influence strongly on the efficiency of the process. The decomposition to levulinic acid and the
`polymerisation to humic acids are the most important factors decreasing the yield of HMF.
`polymerisation to humic acids are the most important factors decreasing the yield of HMF.
`The Scheme 1 is a general one and shows only the most representative products. Antal et al.21
`The Scheme 1 is a general one and shows only the most representative products. Antal et a/.21
`analysed very profoundly the reaction of sugar decomposition in an aqueous solution and they
`analysed very profoundly the reaction of sugar decomposition in an aqueous solution and they
`found four groups of products formed in the course: the isomerisation, the dehydration, the
`found four groups of products formed in the course: the isomerisation, the dehydration, the
`fragmentation and the condensation. Van Dam22 and Cottier23 showed that the aqueous and non-
`fragmentation and the condensation. Van Dam22 and Cottie?3 showed that the aqueous and non-
`aqueous processes led to about 37 products. They demonstrated that the reactions carried out in
`aqueous processes led to about 37 products. They demonstrated that the reactions carried out in
`an aqueous medium provoked the degradation of HMF and that the polymerisation occurred in
`an aqueous medium provoked the degradation of HMF and that the polymerisation occurred in
`both aqueous and non-aqueous media.
`both aqueous and non-aqueous media.
`
`2.1. The mechanism of the fructose dehydration
`2.1. The mechanism of the fructose dehydration
`As it has been already mentioned, Haworth and Jones15 were the first to suggest the mechanism
`As it has been already mentioned, Haworth and Jones15 were the first to suggest the mechanism
`of the dehydration of fructose leading to HMF. Modern studies performed by Van Dam22,
`of the dehydration of fructose leading to HMF. Modern studies performed by Van Dam22,
`Kuster5 and Antal21 showed that the dehydration of hexoses (especially fructose and glucose)
`Kuster5 and Anta121 showed that the dehydration of hexoses (especially fructose and glucose)
`went through one of two possible pathways (Scheme 2). Path ‘a’ included the transformation of
`went through one of two possible pathways (Scheme 2). Path 'a' included the transformation of
`ring systems, while the path ‘b’ is based on acyclic compounds.
`ring systems, while the path 'b' is based on acyclic compounds.
`Antal21 proved experimentally that the mechanism of the HMF formation went through
`Anta121 proved experimentally that the mechanism of the HMF formation went through
`cyclic intermediates. The most significant evidence is:
`cyclic intermediates. The most significant evidence is:
`.
`• Easy formation of HMF from fructose or a fructose part of sucrose
`• Easy formation of HMF from fructose or a fructose part of sucrose
`.
`• 2,5-Anhydro-D-mannose converts easily into HMF1. This compound is a parent aldehyde
`• 2,5-Anhydro-D-mannose converts easily into HMF'. This compound is a parent aldehyde
`
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`©ARKAT USA, Inc
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`General Papers
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`ARKIVOC 2001 (i) 17-54
`ARKIVOC 2001 (i) 17-54
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`to the enol 2.
`to the enol 2.
`.
`• When the reaction was carried out in D2O starting from fructose, deuterium was absent in
`. • When the reaction was carried out in D20 starting from fructose, deuterium was absent in
`HMF. If 3-deoxyglycosulose 3 formed in the course of the reaction, one should expect a carbon-
`HMF. If 3-deoxyglycosulose 3 formed in the course of the reaction, one should expect a carbon-
`deuterium bond due to the keto-enol tautomerism2.
`deuterium bond due to the keto-enol tautomerism2.
`-HO (cid:9)
`Ch OH (cid:9)
`:-.-::: -
`—OH (cid:9)
`1-L01-, (cid:9)
`=0
`HO— (cid:9)
`HO-
`- OH — —OH (cid:9)
`—OH (cid:9)
`—OH (cid:9)
`CH2OH (cid:9)
`CH2OH (cid:9)
`
`—CI-1
`—CFI
`CH2OH
`
`OH
`
`b I -H20
`
`CI-10
`IkOH
`CH
`
`OH
`CH2OH
`
`b I -H20
`
`CHO
`=0
`
`CH
`—OH
`CH2OH
`3
`
`-H2O
`
`CHOH
`
`-h:0
`
`cdo
`
`-H20
`
`
`
`Scheme 2
`Scheme 2
`
`2.2. The kinetics of the HMF synthesis
`2.2. The kinetics of the HMF synthesis
`All described methods of the synthesis of HMF require the utilisation of the thermal dehydration
`All described methods of the synthesis of HMF require the utilisation of the thermal dehydration
`of hexoses in acidic medium. These conditions cause some difficulties in isolation of HMF,
`of hexoses in acidic medium. These conditions cause some difficulties in isolation of HMF,
`especially as HMF is a very active and unstable compound. Kuster5 established factors
`especially as HMF is a very active and unstable compound. Kuster5 established factors
`determining the rate of the formation of HMF:
`determining the rate of the formation of HMF:
`•The sort of the substrate and the hydrolysis degree
`•The sort of the substrate and the hydrolysis degree
`•The kind and the concentration of a catalyst
`•The kind and the concentration of a catalyst
`•The time and the temperature of the reaction
`•The time and the temperature of the reaction
`•The concentration of a polymer and the rate of the polymerisation
`•The concentration of a polymer and the rate of the polymerisation
`•The type of solvent and the stability of HMF in given conditions
`•The type of solvent and the stability of HMF in given conditions
`
`
`
`The synthesis is more efficient and more selective when started from ketohexoses than from
`The synthesis is more efficient and more selective when started from ketohexoses than from
`aldohexoses. For example, the hydrolysis of sucrose in an aqueous medium is much faster than
`aldohexoses. For example, the hydrolysis of sucrose in an aqueous medium is much faster than
`the dehydration and a glucose part is always present in a post-reaction mixture. It is to state that
`the dehydration and a glucose part is always present in a post-reaction mixture. It is to state that
`due to a greater stability of the structure of glucose, it enolyses in a very low degree and the
`due to a greater stability of the structure of glucose, it enolyses in a very low degree and the
`enolisation is a determining factor of the HMF formation from glucose (Scheme 2). Moreover,
`enolisation is a determining factor of the HMF formation from glucose (Scheme 2). Moreover,
`glucose can condense to form oligosaccharides bearing reducing groups, which may react with
`glucose can condense to form oligosaccharides bearing reducing groups, which may react with
`intermediates or with HMF itself. This would result in a cross-polymerisation. Despite, glucose
`intermediates or with HMF itself. This would result in a cross-polymerisation. Despite, glucose
`is still utilised in industry for the preparation of HMF because of its price lower than fructose6.
`is still utilised in industry for the preparation of HMF because of its price lower than fructose6.
`
`ISSN 1424-6376
`ISSN 1424-6376 (cid:9)
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`Page 20
`Page 20 (cid:9)
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`©ARKAT USA, Inc
`©ARKAT USA, Inc
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`

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`General Papers
`General Papers (cid:9)
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`ARKIVOC 2001 (i) 17-54
`ARKIVOC 2001 (i) 17-54
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`The dehydration of hexoses is catalysed by protonic acids as well as by Lewis acids. First
`The dehydration of hexoses is catalysed by protonic acids as well as by Lewis acids. First
`syntheses of HMF were catalysed by oxalic acid7,8,12,15 and till now nearly one hundred inorganic
`syntheses of HMF were catalysed by oxalic acid7'8'12'15 and till now nearly one hundred inorganic
`and organic compounds were positively qualified as catalysts for the HMF synthesis. Cottier6
`and organic compounds were positively qualified as catalysts for the HMF synthesis. Cottier6
`divided catalysts into five groups; they are collected in Table 1.
`divided catalysts into five groups; they are collected in Table 1.
`Iodine catalysis allowed performing the dehydration even from aldohexoses. Bonner et
`Iodine catalysis allowed performing the dehydration even from aldohexoses. Bonner et
`al.24,25 using this method, converted sucrose into HMF in 20% yield. Morikawa26 utilised iodine
`al.24'25 using this method, converted sucrose into HMF in 20% yield. Morikawa26 utilised iodine
`as a catalyst to obtain HMF in 64% yield.
`as a catalyst to obtain HMF in 64% yield.
`
`Table 1. Group of Catalysts
`Table 1. Group of Catalysts
`
`Organic acids
`Organic acids (cid:9)
`Oxalic acid
`Oxalic acid
`Levulinic acid
`Levulinic acid
`Maleic acid
`Maleic acid
`p-TsOH
`p-TsOH
`
`
`
`
`
`
`
`
`
`
`
`Th and Zr ions
`Th and Zr ions
`
`Salts
`Inorganic acids
`Salts (cid:9)
`Inorganic acids (cid:9)
`(NH4)2SO4/SO3
`Phosphoric acid
`(NH4)2504/503
`Phosphoric acid
`Pyrid/PO4 -3
`Sulphuric acid
`Pyrid/PO4 -3
`Sulphuric acid
`Hydrochloric acid Pyrid/HCl
`Pyrid/HC1
`Hydrochloric acid
`Iodine or
`Aluminium salts
`Aluminium salts
`Iodine or
`Hydroiodic
`acid
`Hydroiodic acid
`generated in situ
`generated in situ
`
`
`
`
`
`
`
`
`Zirconium phosphate
`Zirconium phosphate
`Ions: Cr, Al., Ti, Ca,
`Ions: Cr, Al., Ti, Ca,
`In
`In
`ZrOCl2
`ZrOC12
`Vo(SO4)2, TiO2
`Vo(SO4)2, T102
`V-porphyrine
`V-porphyrine
`Zr, Cr, Ti-porphyrine
`Zr, Cr, Ti-porphyrine
`
`Lewis acids Others
`Lewis acids Others
`Ion-exchange resins
`ZnCl2
`ZnC12
`Ion-exchange resins
`AlCl3
`Zeolites
`A1C13
`Zeolites
`
`BF3
`BF3
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`The use of organic and inorganic salts in the synthesis of HMF was the subject of numerous
`The use of organic and inorganic salts in the synthesis of HMF was the subject of numerous
`works. Mednic27,28 proposed to utilise ammonium phosphates (the yield 23%), triethylamine
`works. Mednic27'28 proposed to utilise ammonium phosphates (the yield 23%), triethylamine
`phosphate (36%) or pyridinium phosphate. The latter allowed obtaining HMF in 44% yield.
`phosphate (36%) or pyridinium phosphate. The latter allowed obtaining HMF in 44% yield.
`Nakamura29 invented the catalysis with zirconium phosphate and zirconyl chloride, a further
`Nakamura29 invented the catalysis with zirconium phosphate and zirconyl chloride, a further
`development of this method30 allowed improving the yield up to 90%.
`development of this method3° allowed improving the yield up to 90%.
`Fayet and Gelas31 utilised various pyridinium salts: poly-4-vinylpyridinium hydrochloride as
`Fayet and Gelas31 utilised various pyridinium salts: poly-4-vinylpyridinium hydrochloride as
`well as pyridinium
`trifluoroacetate, hydrochloride, hydrobromide, perbromate and p-
`well as pyridinium trifluoroacetate, hydrochloride, hydrobromide, perbromate and p-
`toluenesulfonate. Starting from fructose, they obtained HMF in 70% average yield.
`toluenesulfonate. Starting from fructose, they obtained HMF in 70% average yield.
`Smith32 as well as Garber and Jones33 proposed utilising ammonium sulphate; Hales et al.34
`Smith32 as well as Garber and Jones33 proposed utilising ammonium sulphate; Hales et a/.34
`as well as scientists from Atlas Powder Lab.35 applied chromium trichloride or zinc chloride.
`as well as scientists from Atlas Powder Lab.35 applied chromium trichloride or zinc chloride.
`Works concerning the application of ion-exchange resins for the synthesis of HMF are the most
`Works concerning the application of ion-exchange resins for the synthesis of HMF are the most
`numerous. Nakamura36 investigated the influence of a strongly acidic ion exchange resin and
`numerous. Nakamura36 investigated the influence of a strongly acidic ion exchange resin and
`obtained HMF in 80% yield. Gaset et al.37,38 utilised Levatit® SPC-108, to form HMF in 70-80%
`obtained HMF in 80% yield. Gaset et al.37'38 utilised Levatit® SPC-108, to form HMF in 70-80%
`yield. Researchers from Noguchi Institute39 patented the use of ion-exchange resins such as
`yield. Researchers from Noguchi Institute39 patented the use of ion-exchange resins such as
`Amberlite® IR-116 or Diaion® PK-228 cross-linked with divinylbenzene. Some authors40,41
`Amberlite® IR-116 or Diaion® PK-228 cross-linked with divinylbenzene. Some authors40'41
`claimed Diaion® PK-216 to be the most efficient. In both cases HMF was obtained in 90% yield.
`claimed Diaion® PK-216 to be the most efficient. In both cases HMF was obtained in 90% yield.
`Apart from the methods described above, it is worth to mention works by Mercadier,42
`Apart from the methods described above, it is worth to mention works by Mercadier,42
`
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`ARKIVOC 2001 (i) 17-54
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`Rigal,43 El-Hajj44 or Rapp.20 Their syntheses were also based on ion exchange and gave HMF in
`Riga1,43 El-Hajj44 or Rapp.2° Their syntheses were also based on ion exchange and gave HMF in
`high yields.
`high yields.
`The type of solvent and its influence on the efficiency of the dehydration is closely connected
`The type of solvent and its influence on the efficiency of the dehydration is closely connected
`with temperature conditions. Cottier6 divided methods into 5 groups depending on the type of
`with temperature conditions. Cottiers divided methods into 5 groups depending on the type of
`solvent and the temperature of the process:
`solvent and the temperature of the process:
`•Aqueous processes carried out at temperatures below 200 °C
`•Aqueous processes carried out at temperatures below 200 °C
`•Aqueous processes carried out at temperatures over 200 °C
`•Aqueous processes carried out at temperatures over 200 °C
`•Processes in non-aqueous medium
`•Processes in non-aqueous medium
`•Processes in mixed solvents
`•Processes in mixed solvents
`•Processes without solvent and microwave processes
`•Processes without solvent and microwave processes
`
`The methods belonging to the first group are very convenient in the ecological point of view,
`The methods belonging to the first group are very convenient in the ecological point of view,
`but unfortunately they are not very efficient. Studies performed by laboratories of Suddeutsche
`but unfortunately they are not very efficient. Studies performed by laboratories of Suddeutsche
`Zucker showed that the maximum yield of HMF obtained via Rapp’s procedure20 is about 30%.
`Zucker showed that the maximum yield of HMF obtained via Rapp's procedure2° is about 30%.
`Cottier45 reported that the application of ion-exchange resins in an aqueous medium allowed
`Cottier45 reported that the application of ion-exchange resins in an aqueous medium allowed
`formation of HMF in satisfactory yield. Depending on the mode of the isolation, he obtained it in
`formation of HMF in satisfactory yield. Depending on the mode of the isolation, he obtained it in
`28% or 26% yield. They observed no influence of high dilution on the efficiency.
`28% or 26% yield. They observed no influence of high dilution on the efficiency.
`The second group of methods is based on pyrolitic processes. It was noted that the yield was
`The second group of methods is based on pyrolitic processes. It was noted that the yield was
`increased in these reactions up to 58% and that the time of the reaction was shortened. Soluble
`increased in these reactions up to 58% and that the time of the reaction was shortened. Soluble
`polymeric products were detected instead of insoluble humic acids. Non-aqueous solvents
`polymeric products were detected instead of insoluble humic acids. Non-aqueous solvents
`require high dilution system; owing to the hydrophilic character of reagents. Various solvents
`require high dilution system; owing to the hydrophilic character of reagents. Various solvents
`were tested: Bonner24'25 and Shur et al.46 carried out the reaction in DMF, Brown47 — in
`were tested: Bonner24,25 and Shur et al.46 carried out the reaction in DMF, Brown47 – in
`acetonitrile. Morikawa26 proposed the application of quinoline and Smythe and Moye48,49
`acetonitrile. Morikawa26 proposed the application of quinoline and Smythe and Moye48'49
`performed the reaction in polyglycol ethers. The greatest number of papers described the
`performed the reaction in polyglycol ethers. The greatest number of papers described the
`utilisation of DMSO as a solvent in the HMF synthesis. Nakamura,29'30'36 Noguchi Institute39 and
`utilisation of DMSO as a solvent in the HMF synthesis. Nakamura,29,30,36 Noguchi Institute39 and
`Gaset et al.37,38 carried out reactions catalysed by ion exchange resins in DMSO. Mussau50
`Gaset et 0.37'38 carried out reactions catalysed by ion exchange resins in DMSO. Mussau50
`performed the reaction without a catalyst, carrying it out in DMSO, too. Problems concerning the
`performed the reaction without a catalyst, carrying it out in DMSO, too. Problems concerning the
`solubility of hexoses in organic solvents were resolved by the application of mixed-solvent
`solubility of hexoses in organic solvents were resolved by the application of mixed-solvent
`(water-organic) systems. Chemists worked on these methods for a long time, Teunissen51, in
`(water-organic) systems. Chemists worked on these methods for a long time, Teunissen51, in
`1931 proposed to use homogeneous systems for the synthesis of HMF. Now numerous papers
`1931 proposed to use homogeneous systems for the synthesis of HMF. Now numerous papers
`describing various mixed systems have appeared. Peniston52 utilised n-butanol, Mednic27,28 and
`describing various mixed systems have appeared. Peniston52 utilised n-butanol, Mednic27'28 and
`Hales34 dioxane. Atlas Powder Co Laboratories35 and Kuster53-56 tested polyethylene glycols.
`Hales34 dioxane. Atlas Powder Co Laboratories35 and Kuster53-56 tested polyethylene glycols.
`The last method allowed a decrease in the degree of HMF degradation to levulinic acid.
`The last method allowed a decrease in the degree of HMF degradation to levulinic acid.
`Reactions run without a solvent resulted in diminished formation of levulinic acid and humic
`Reactions run without a solvent resulted in diminished formation of levulinic acid and humic
`acids. Fayet and Gelas31 worked with equimolar amounts of hexoses and pyridinium salts to
`acids. Fayet and Gelas31 worked with equimolar amounts of hexoses and pyridinium salts to
`obtain HMF in 70% yield. Neyret57 tested the use of lower amounts of pyridinium salts other
`obtain HMF in 70% yield. Neyret57 tested the use of lower amounts of pyridinium salts other
`than those used by Fayet and Gelas. The best results were obtained with pyridinium oxalate,
`than those used by Fayet and Gelas. The best results were obtained with pyridinium oxalate,
`although the yield did not exceed 20 %, the ecological value of this method allowed using it in
`although the yield did not exceed 20 %, the ecological value of this method allowed using it in
`an industrial scale. Cottier45 worked out a nice, clean and efficient laboratory method of
`an industrial scale. Cottier45 worked out a nice, clean and efficient laboratory method of
`preparation of HMF. According to his description the irradiation with microwaves of aqueous
`preparation of HMF. According to his description the irradiation with microwaves of aqueous
`fructose (or sucrose) mixed with inorganic phosphates for 3 minutes gave HMF in 28%.
`fructose (or sucrose) mixed with inorganic phosphates for 3 minutes gave HMF in 28%.
`Chemists continue studies on HMF synthesis. Ponder and Richards58 tested the chemical
`Chemists continue studies on HMF synthesis. Ponder and Richards58 tested the chemical
`behaviour of D-glucose in the vacuum pyrolysis conditions, in the presence of such salts as
`behaviour of D-glucose in the vacuum pyrolysis conditions, in the presence of such salts as
`
`ISSN 1424-6376
`ISSN 1424-6376 (cid:9)
`
`Page 22
`Page 22 (cid:9)
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`©ARKAT USA, Inc
`©ARKAT USA, Inc
`
`Petitioners' Exhibit 1005, Page 6 of 38
`
`

`
`General Papers
`General Papers (cid:9)
`
`ARKIVOC 2001 (i) 17-54
`ARKIVOC 2001 (i) 17-54
`
`sodium chloride, calcium acetate, and bases such as sodium or calcium hydroxide. The reaction
`sodium chloride, calcium acetate, and bases such as sodium or calcium hydroxide. The reaction
`lasted 30 minutes and it led to several anhydro-fructofuranoses and to HMF. Nakama et al.59
`lasted 30 minutes and it led to several anhydro-fructofuranoses and to HMF. Nakama et al.59
`studied the reaction of various disaccharides and monosaccharides such as: O4-β-D-
`studied the reaction of various disaccharides and monosaccharides such as: 04-13-D-
`galactopyranosyl