rte
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`
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`rates 1
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`Fire
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`Patented Jan. 1, 1953
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`3,071,599
`PREPARATHGN 6F HYDROXYB'IETHYL
`FURFURAL
`Ralph A. Hales, West (Ihester, Pa, John W. Le Maistre,
`(Jiaymont, DeL, and George Gtto Orth, lira, Seattle,
`Wasln, assignors to Atlas Chemical Industries, Inc.,
`Wilmington, DeL, a corporation of Delaware
`No Drawing. Filed Feb. 25, M59, Ser. No. 7§5,3‘53
`8 Claims. (Cl. Zed-347.8)
`
`This invention relates to the preparation of hydroxy
`methyl furfural and more particularly to an improvement
`in the process of preparing hydroxymethyl furfural by the
`dehydration of hexoses.
`That hydroxyrnethyi furfural is one of the products
`formed when hexoses are subjected to dehydrating condi
`tions is well known in the chemical art and it has been
`proposed repeatedly to utilize this dehydration reaction
`in a commercially practical manner for the production
`of hydroxymethyl furfural. Reference is made, for ex
`ample, to U.S. Patent No. 2,750,394 wherein the kinetics
`of the reaction are extensively considered and a process
`for carrying out the dehydration of keto hexoses in the
`presence of aqueous solutions of lower aliphatic mono
`hydric alcohols is disclosed and claimed. Acids and acid
`generating salts are known to be useful catalysts for the
`dehydration reaction.
`It is an object of the present invention to provide an
`improved process for converting hexoses to hydroxy
`methyl furfural.
`Another object is to provide a process for converting
`hexoses to hydroxymethyl furfural by catalytic dehydra
`tion in reaction media of low water content.
`A further object is to provide a process for dehydrat
`ing hexoses to hydroxymethyl ‘furfural while avoiding
`the formation and deposition of insoluble humins.
`The above and other objects will become more ap
`parent in the course of the following description of the
`invention and in the appended claims.
`In accordance with the invention, a hexose is converted
`to hydroxymethyl furfural by acid-catalyzed dehydration
`in a reaction medium comprising water and an organic
`liquid containing ketone or ether oxygen. More particu
`larly the organic liquid is selected from the group consist
`ing of acid-stable aliphatic ketones and acid-stable ali
`phatic ethers of normal boiling point no greater than
`about 280° C.
`The process of the invention is applicable to the con
`version of both keto- and aldo-hexoses. Moreover, since
`the dehydration reaction is acid-catalyzed and conducted
`at an elevated temperature, disaccharides and oligosac
`charides which readily hydrolyze to ketoses, aldoses or
`mixture of the two under such conditions, may be em
`ployed as starting materials. Suitable sugars for conver
`sion thus include glucose, fructose, sorbose, mannose,
`sucrose and maltose. There may also be employed mix
`tures rich in sugars, particularly for example, molasses,
`either high test or blackstrap, and starch conversion
`liquors containing dextrose and dextrose polymers.
`Throughout this speci?cation and in the appended claims
`the term hexose will be used to include hexose polymers
`which yield hexoses on acid hydrolysis.
`It is Well known that the conversion of hexoses to
`hydroxymethyl furfural is catalyzed by acids, and acid
`generating or acid~reacting compounds. The catalyst em
`ployed in processes embodying the improvement com
`prising the present invention may thus be an inorganic
`or organic acid such, for example, as hydrochloric acid,
`sulfuric acid, phosphoric acid, toluene sulfonic acid or
`acetic acid. Salts of weak bases and strong acids are
`acid-reacting and e?ective as catalysts. Aluminum chlo
`ride, zinc chloride and chromium chloride may be named
`
`2
`as representative of such salts. Furthermore acid-react
`ing salts may be employed in conjunction with acids as
`catalysts for the reaction. The improved process of the
`invention is independent of the particular catalyst selected
`and is applicable in the presence of any of the foregoing
`types which will ‘be generically referred to as acid cat
`alysts.
`As is well recognized in the art the formation of hy
`droxymethyl furfural is only one of several competing re
`actions proceeding when hexoses are subjected to de
`hydration conditions, others of which include the destruc
`tion of formed hydroxymethyl furfural to yield levulinic
`acid, formic acid, humin and colored bodies of undeter
`mined structure. Accordingly any process for preparing
`hydroxymethyl furfural by sugar dehydration includes
`conventional steps for recovering the sought product ‘from
`the reaction mixture. Liquiddiquid extraction processes
`and/or distillation may, for example, ‘be employed.
`Such separation and recovery steps are not part of the
`present invention but practice of the invention results in
`reaction product mixtures which are readily adapted to
`the recovery of high purity hydro-xymethyl furfural.
`As taught in the prior art of sugar dehydration, it is
`frequently advisable to interrupt the conversion to hy
`droxymethyl furfural when only part of the sugar has
`been dehydrated, thus maximizing the yield of product
`based on sugar actually consumed. The unreacted sugars
`after separation of hydroxymethyl furfural may be re
`cycled to the dehydration reactor. The improvement in
`accordance with the present invention may be employed
`in such a recycling process if desired.
`‘
`The before mentioned objects of the invention are ac
`complished by carrying out the acid catalyzed dehydra
`tion step, of an otherwise conventional process for pro~
`ducing hydroxyrnethyl furfural from a hexose, in the
`presence of a medium comprising a mixture which con
`tains from 5% to 70% by weight of water and corre
`spondingly from 30% to 95% by weight of an acid-stable
`aliphatic ketone or an acid-stable aliphatic ether of boil
`ing point no greater than about 280° C. The ether or
`ketone may be acyclic or cyclic and substituted or unsub
`stituted as long as any substituent groups do not render
`the solvent reactive with the acid catalyst or with the
`hexose carbonyl groups. It is not essential that the ke
`tone or ether be miscible with water or with the sugar
`solution formed by the hexose and water of the reaction
`medium. In case immiscibility is encountered vigorous
`agitation is employed during the dehydration reaction to
`maintain intimate contact between the components of the
`reaction medium, the hexose and the acid catalyst.
`Among the ketones and ethers which may be employed
`in accordance with the invention are methyl isobutyl ke
`tone, mesityl oxide, dichlorethyl ether, dioxane, glycol
`monornethyl ether, symmetrical dimethyl dioxane, tetra
`hydropyran, tetrahydro-Z methyl pyran, and the like.
`Preferably the ketone or ether is one with a normal boil
`ing point below 140° C. vFurthermore it is preferred that
`the reaction medium contain at least 50% of the organic
`liquid. A particularly preferred reaction medium is a
`mixture of dioxane and water containing between 65%
`and 90% dioxane.
`The following examples illustrate how the invention is
`employed in the conversion of hexoses to hydroxymethyl
`furfural.
`
`Example I
`C0nversion.~—-A charge consisting of 290 grams p-di
`oxane and 197.2 grams high test molasses, containing
`sugar representing 145 grams hexose and 38.6 grams
`water, together with 0.72 gram aluminum chloride hexa
`hydrate and 0.83 gram hydrochloric acid was reacted in
`29 batches in small tantalum bombs. Each charged
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`bomb was shaken in an oil bath at 195° C. for 87 seconds
`and cooled quickly by immersion in a cold bath. The
`reacted mixtures were combined for analysis and recovery
`of the formed hydroxymethyl furfural. The product
`contained no material insoluble in the reaction medium.
`By analysis with Fehling’s solution after hydrolysis the
`conversion liquor was found to contain 43.6 grams sugar
`indicating that 69.9% of the sugar charged had been
`converted. A portion of the conversion liquor was sub
`jected to a S-stage countercurrent fractionation between
`water and butanol to remove interfering substances and
`the hydroxymethyl furfural determined quantitatively by
`ultraviolet absorption at 2840 angstroms. The amount
`found corresponded to 42.3 grams in the entire product,
`equivalent to 41.7% of the theoretical yield on sugar
`charged to the reaction and 59.7% on the sugar con
`sumed.
`Recovery.——ln the ensuing description all reported
`weights of material in process have been corrected for
`samples removed for analysis and therefore may be re
`ferred to the initial charge Weight of molasses equivalent
`to 145.0 grams hexose. The dioxane was removed by
`distillation under vacuum and the residue (165 grams)
`taken up in 560 grams of water. 27.5 grams of an ad
`' sorbent clay (Super Filtrol) was stirred into the solution,
`which contained some suspended insoluble humin, at
`room temperature and ?ltered to remove insoluble matter.
`The ?lter cake was well washed with water, the washings
`combined with the ?ltrate, and the whole concentrated,
`under vacuum to a residue of 166 grams. The residue
`was partitioned between mesityl oxide and water to sep
`arate sugar (aqueous phase) from the bulk of the hy
`droxymethyl furfural (mesityl oxide phase). The
`aqueous phase was found by analysis to contain 38.7
`grams sugar and 2.6 grams hydroxymethyl furfural and
`was suitable for recycling to the conversion process.
`The mesityl oxide phase was neutralized with 6.5
`' grams of sodium bicarbonate and extracted with water to
`remove the formed sodium salts. The mesityl oxide was
`then taken off under vacuum and the residue diluted with
`water to a weight of 85.5 grams. By analysis this solu
`tion contained 38.6 grams hydroxymethyl furfural. The
`pH of the solution was adjusted to 7.0 with a small
`amount of sodium bicarbonate and gradually added to
`a heated still under vacuum. The distillate weighed
`41.8 grams and was found to contain, by analysis, 35.0
`"grams of hydroxymethyl furfural.
`Thus 82.8% of the
`hydroxymethyl furfural in the conversion liquor was re
`covered in purity of 83.8%. Another 6.1% of the
`formed hydroxymethyl furfural was available to be re
`cycled with the unconverted sugar and was therefore ulti
`mately recoverable.
`Inasmuch as thepresent- invention is concerned only
`with the conversion step of the hydroxymethyl furfural
`process, the remaining illustrative examples will not in
`clude a description of the process for recovering the ?nal
`product from the conversion liquor. The method em
`ployed in Example I above, or other methods readily
`devisable from the known properties of hydroxymethyl
`furfural and related sugar derivatives obtainable as by
`products in dehydration reactions, may be applied to the
`conversion products of any of the examples.
`.
`
`Example II '
`A 400 ml. stainless steel autoclave, equipped with a
`solenoid-operated plunger for agitation was charged with
`80 grams of fructose, 160 grams of dioxane and 25 grams
`of water. The autoclave was immersed in a heated wax
`bath and taken to 180° C. under'agitation in about 15
`minutes, at which time 1.4 ml. of 3.6% hydrochloric
`acid solution was injected into the charge under nitrogen
`pressure. After 4 minutes at temperature the auto
`clave was cooled quickly to terminate the reaction by
`transferring to a cold ethylene glycol bath. The auto
`clave was opened and the contents were mixed with those
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`Water .._‘- _______________ __. 34%. '
`7
`Catalyst ________________ _. AlCl3-6H2O, 0.22%.
`Reaction conditions ...... __ 3 minutes at 210° "C.
`Sugar remaining _________ __ 20.8%.
`HMF (on sugar charged) ___ 41.6% of theory. .
`HMF (on sugar consumed) _. 52.5% of theory.
`
`4
`of another run made in the same manner. The mixture
`of the two runs was subjected to analysis. No insoluble
`humins were present. The conversion liquor contained
`unreacted sugar in amount, corresponding to 16.3% of
`that originally charged and hydroxymethyl furfural in
`amount corresponding to 57.3% of the theoretical yield
`based on hexose charged to the autoclave. Based on
`sugar reacted, the yield of hydroxymethyl furfural was
`68.5% of theory.
`Further illustrating the invention are the following
`examples, all of which were carried out in sealed glass
`tube reactors. The general procedure was to charge ap
`proximately 1 gram of the named sugar together with the
`indicated amounts of solvents and catalyst, each expressed
`as a percentage of the hexose (or hexose equivalent),
`into a glass tube. The tube was immersed in a bath of
`molten wax at the indicated temperature, shaken there
`for the indicated length of time and transferred to a
`bath of cold ethylene glycol to terminate the reaction.
`The cooled tube was then opened and the contents
`analyzed for sugar and hydroxymethyl furfural (HMF)
`contents from which the yields, percent of theory based
`on hexose charged and hexose consumed, were calculated.
`Example III
`
`Hexose source _________ __ Sorbose (taken as 100%).
`Organic liquid _________ .._ Glycol monomethyl ether,
`96%.
`Water __________ __' ____ __ 132%.
`Catalyst ______________ __ Sulfuric acid, 1.0%.
`Reaction conditions ____ __ 3 minutes at 180° C.
`Sugar remaining _______ __ 21.6%.
`HMF (on sugar charged) _.. 52.1% of theory.
`HMF (on sugar con
`sumed) ____________ __ 66.4% of theory.
`Example IV
`
`Hexose source _________ __ Sorbose (taken as 100%).
`Organic liquid _________ __ Dichlorethyl ether, 99%.
`Water ________________ __ 132%.
`Catalyst ______________ __ Sulfuric acid, 1%.
`Reaction conditions ____ __ 1.8 minutes at 180° C.
`Sugar remaining _______ __ 20.5%.
`HMF (on sugar charged) __ 52.2% of theory.
`HMF (on sugar con
`sumed) ____________ _.. 65.7% of theory.
`
`.
`
`Example V
`
`Hexose source ________ __ Sorbose (taken as 100% ).
`Organic liquid _________ _. Methyl isobutyl ketone, 96%.
`Water _______________ __ 132%.
`Catalyst ______________ __. Sulfuric acid, 1%.
`Reaction conditions ____ __ 3.0 minutes at 180° C.
`Sugar remaining _______ _.. 18.5 % .
`HMF (on sugar charged) _ 52.5 % of theory.
`(on sugar consumed) 64.4% of theory.
`Example VI
`Hexose source __________ __ Sorbose (taken as,100%).
`Organic liquid ___________ _. Mesityl oxide, 152%.
`Water __________________ _. 80%.
`Catalyst ________________ _. Hydrochloric acid, 0.25%.
`Reaction conditions ______ __ 2.0 minutes at 180° C.
`Sugar remaining _________ __ 25.5%.
`HMF (on sugar charged) __-. 56.4% of theory.
`HMF (on sugar consumed) _. 75.7% of theory.
`Example VII
`Hexose source __________ __ Glucose (taken as 100%).
`Organic liquid ___________ _. Dioxane, 208%.
`
`Petitioners' Exhibit 1017, Page 2 of 4
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`Example VIII
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`3,071,599
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`6 .
`Example XIII
`
`Hexose source g;____ 'Glucose (taken as 100%).
`Organic liquid __.____. Sym. dimethyl dioxane, 159%.
`Water ____________ ... 82%.
`Catalyst __________ __ AlCl3-6H2O—0.22%; HCl, 0.12%.
`Reaction conditions ._ 2.5 minutes at 210° C.
`Sugar remaining ___.... 21.1%.
`HMF (on s u g a r
`charged) _______ _. 40.9% of theory.
`HMF (on sugar con
`sumed) _________ _. 51.8% of theory.
`
`5
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`Hexose source _______ __ Sorbose (taken as 100%).
`Organic liquid ________ _. Triethylene glycol, 201%.
`Water __________ _.V_____ 36%.
`Catalyst _____________ _. HCl, 0.13%.
`Reaction conditions _____ 3 minutes at 180° C.
`Sugar remaining ______ _- 16.4%.
`H M F (o n s u g a 1'
`charged) _________ __ 66.9% of theory.
`I-IMF (on sugar con~
`sumed) __________ __ 80.0% of theory.
`
`Example IX
`
`Hexose source _.2 ____ __ Sucrose (hexose equiv. taken
`as 100% ).
`Organic liquid __.__‘_____. Dioxane, 195%.
`
`Water ______________ __ 35%.
`.
`Catalyst _____________ _. CrCl3'6H2O, 0.24%; HCl,
`0.12%.
`Reaction conditions _____ 4 minutes at 210° C.
`Sugar remaining ______ _. 17.4%.
`H M F (o n s u g a r
`charged) _________ .._ 46.8% of theory.
`HMF (on sugar con
`sumed) __________ __ 56.6% of theory.
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`It is to be emphasized that the improvement in con_
`version of hexoes to hydroxymethyl furfural in accord
`ance with the invention is effected by virtue of the com
`position of the reaction medium. The absolute values
`of extent of conversion and yield of hydroxymethyl
`furfural Will vary with the choice of sugar, catalyst, and
`reaction conditions but ‘by employing the water-organic
`liquid reaction medium ‘as above-de?ned and illustrated
`in place of prior art reaction media such, for example,
`as Water or aqueous alcohol mixtures, the improved re
`sults will be obtained.
`In general, when employing the reaction media of
`the invention it is possible to work with higher sugar
`concentrations than was considered desirable in the prior
`art with concomitant savings in processing costs. A pre
`'ferred range of sugar concentrations in the interest of
`maximum yield of hydroxymethyl furfural and avoid
`ance of undue dilution is from 25% to 40% by weight
`of the total conversion liquor. At concentrations higher
`than 50% there is a marked decrease in hydroxymethyl
`furfural yield for any given sugar consumption and it is
`preferred to avoid such high concentrations.
`Choice of catalyst, amount of catalyst, nature of the
`sugar, reaction temperature and reaction time all interact
`in determining the amount of sugar reacted in a conver
`‘sion cycle. At temperature below about 150° C. con
`version is unduly slow and it is therefore considered
`advisable to work above that temperature. At tempera
`tures above about 220° C. thermal degradation other
`than the desired dehydration increases markedly and such
`temperatures should be avoided. A preferred, though not
`highly critical, range is from 180° C. to 210° C. In gen
`eral, the ketoses may be economically converted at some
`what lower temperatures than the alidoses or hydrolyza~
`ble disaccharides.
`As has been noted by prior investigators, as the amount
`of sugar converted in ‘a single cycle increases, the yield
`of hydroxymethyl iurfural based on sugar consumed de
`creases. The choice of extent of conversion per pass thus
`involves a balancing of the cost of recovering and re
`cycling larger amount of unreacted sugar against the cost
`of letting more of the sugar go to unwanted by-products
`instead of to hydroxymethyl furfural. Employing a re
`action medium as disclosed and claimed in the present
`invention permits carrying the conversion ‘further before
`the hydroxy-methyl 'furfural yield drops to an uneconomi
`cally low value than when employing the aforesaid prior
`art reaction media.
`Adjustment of the several reacting conditions to the
`optimum value when employing the principle of the in
`vention is well within the skill of the chemical art having
`regard 'to the foregoing description and illustrative
`examples.
`What is claimed is:
`1. In the process of preparing hydroxymethyl furfural
`by the acid catalyzed dehydration of a hexose at elevated
`temperature the improvement which comprises carrying
`out the said acid catalyzed dehydration step in the pres
`ence of ‘a reaction medium consisting essentially of from
`50% :to 90% :by Weight of dioxane and correspondingly
`from 10% to 50% by weight of water in the temperature
`range of ‘150° C. to 220° C., the concentration of hexose
`
`Example X
`
`Hexose source _______ __ Sucrose (hexose equiv. taken
`as 100% ).
`Organic liquid ________ _. Tetrahydro - 2 - methyl furan,
`164%.
`Water ______________ __ 80%.
`Catalyst _____________ _. AlCl3-6H2O, 0.22%; HCl,
`0.12%.
`Reaction conditions _____- 2.0 minutes‘ ‘at 210° C.
`Sugarremaining ______ _. 18.5%.
`H M F (0 n s u g a r
`charged) _________ __ 43.8% of theory.
`HMF (on sugar con~
`sumed) __________ __ 53.7% of theory.
`
`Exam'ple XI
`
`Hexose source _______ __ Mixed 1 (hexose equiv. taken
`as 100% ).
`Organic liquid ________ _. Dioxane, 131%.
`Water ______________ __ 36%.
`Catalyst _____________ _.'AlCl3-6H2O, 0.45%; HCl,
`0.50%.
`Reaction conditions __-__ 1.8 minutes at 210° C.
`Sugar remaining ______ _. 20.8%.
`H M F (o n s u g a 1'
`charged) _________ __ 51.0% of theory.
`HMF (on sugar con
`sumed) __________ __ 64.4% of theory.
`1High test molasses plus sugar recovered from a prior
`high test molasses conversion. The recovered sugar repre
`sented 30% of the total.
`
`Example XII
`
`Hexose source _______ __ Sucrose (hexose equiv. taken
`as 100% ).
`Organic liquid ________ _. Dioxane, 152%.
`Water ________ __,______ 78%.
`Catalyst _____________ _. AlCl3-6H2O, 1.35%; HCl,
`0.18%.
`Reaction conditions _____ 23 minutes at 150° C.
`Sugar remaining ______ _. 27.1%.
`H M F (o n s u g a r
`charged) _________ .._ 40.2% of theory.
`HMF (on sugar con
`sumed) __________ __ 55.2% of theory.
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`Petitioners' Exhibit 1017, Page 3 of 4
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`3,071,599
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`in the reaction charge lying between the inclusive limits
`of 25% and 50%.
`2. The process of claim 1 wherein the hexose is a
`ketose.
`3. The process of claim 2 wherein the catalyst is a
`mineral acid.
`4. The process of claim 1 wherein the hexose is hy
`drolyzed sucrose.
`5. The process of claim 4 wherein the catalyst is a
`mixture of hydrochloric acid and aluminum chloride.
`6. In the process of preparing hydroxymethyl furfural
`by the acid catalyzed dehydration of ‘a hexose at elevated
`temperature the improvement which comprises carrying
`out the dehydration in ‘a reaction medium comprising a
`mixture which contains from 5% to 70% by weight of
`water and correspondingly from 30% to 95% by Weight
`of an organic liquid selected from the Igroup consisting
`of dioxane, mesityl oxide, ‘glycol monomethyl ether, di
`chlorethyl ether, methyl isobutyl ketone, dimethyl di
`oxane, tetrahy-dromet‘hyl ‘?unan and triethylene glycol.
`
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`7. The improved process of claim 6 wherein the said
`organic liquid is. dioxane.
`8. The improved process of ,claim 6 wherein the said ‘
`organic liquid is mesityl oxide.
`
`References Cited in the ?le of this patent
`UNITED STATES PATENTS
`Haworth ____________ ._ Feb. 28, 1950
`Penniston _______ _‘_______ June 16, 1956
`
`2,498,918
`2,750, 394
`
`OTHER REFERENCES
`Dunlop: “The Furans,” page 410, Reinhold Publish
`ing Corp. (1953).
`Fieser: “Organic Chemistry,” (Third Edition, 1956),v
`page 133.
`.
`Weissberger: Technique of Organic Chemistry, vol.
`III, pt. 1 (1956), page 302.
`.
`.' "
`
`Petitioners' Exhibit 1017, Page 4 of 4