### US 20140187802A1 

# (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0187802 A1 Mikochik et al. (43) Pub. Date: Jul. 3, 2014

(54) EFFICIENT, HIGH-YIELD CONVERSION OF (60) Provisional application No. 61/818,418, ?led on May SACCHARIDES INA PURE OR CRUDE FORM 1, 2013, provisional applicationNo. 61/714,225, ?led TO 5-(CHLOROMETHYL)-2-FURALDEHYDE on Oct. 16, 2012.


### (71) ApplicantszPeter Mikochik, Groton, CT (US); Publication Classi?cation Aviad Cahana, Albuquerque, NM (US); Edward Nikitin, Albuquerque, NM (51) Int. Cl 

### (US); Jeremy Standiford, Rio Rancho, C07D 307/48 (2006.01) NM (US); Kyle Ellis, Albuquerque, NM (52) US. Cl. (US); Luzheng Zhang, Albuquerque, CPC

.................................... C07D 307/48 (2013.01)
NM (US); Timothy George, USPC

......................................... .. 549/483; 422/131 

### Albuquerque, NM (US) (57) ABSTRACT 

## (72) Inventors: Zagghélg?llcligklki?tlolggi: ;(US)_ Thepresentinventiondescribesmethodsandapparatuses for EdwardNikiti’n Aug u; u’e NM ’ thesynthesisof5-(chloromethyl)-2-furaldehyde (CMF)from

_ ’

. q q
. ’ saccharides inpure or crude form, the method comprising: (a) (US), Jeremy Standlford, Rio Rancho,

. . . .

_ . continuously contactlng saccharides 1n pure or crude form, NM (US), Kyle Ellis, Albuquerque, NM

. . .

_ hydrochloric a01d, and an orgamc solvent, by way of a con (US), Luzheng Zhang, Albuquerque,

. . . NM (US)_ Timoth Geor e t1nuous, biphasic-?ow reactor assembly at a temperature Alb ’ NM {Us g ’ from about 60 degrees C. to about 200 degrees C. and pres uquerque’ sures from about 1 atmosphere to about 20 atmospheres, such

_ that CMF is produced; (b) separating 5-(chloromethyl)-2 

### (21) Appl' NO" 14/195’513 furaldehyde by liquid/liquid and solid/liquid phase separa

. _ tion; (0) producing at least ?vekilograms perdayWithat least (22) Flled' Man 3’ 2014 50% yield. Embodiments of the present invention can pro

. . duce CMF in a continuous fashion, Withhigh yield andWith Related U's' Apphcatlon Data out degradation of CMF to such side products as 5-(hy 

### (63) Continuation-in-partofapplicationNo. PCT/US2013/ droxymethy1)furfura1 (HMF), 2-(2-hydroxyacety1)furan 057795, ?led on Sep. 3, 2013. 

### (HAF) and levulinic acid (LA).

## Jul. 3, 2014 Sheet 1 0f 6 US 2014/0187802 A1 

## PatentApplication Publication


# COEmbcwucOU Eu<

H .wE 

# VEB wwEopm u._._._ AI 

# cormcmqwm 28328 .o_ 

# 85233 28323:

.0

8 .ME 

# cormccom

## Jul. 3, 2014 Sheet 2 0f 6 US 2014/0187802 A1 

## PatentApplication Publication



# N .wE 

# corEmem 0P Al 

# $>oEwm Hme.u 

# cormELom

_wmmw> coruwwm

.u 

# wmwgm

wmwgm 

# msowsc<.w

# m m .9; 

# U 32¢ _2_om w. Lo m



# wH Eqwm AcoBmELoi ¢_>_u 

# 232<2_om

.m as: m

@223 2cmm5 m



# 6meme 28328: .2 82: 2%:


# corEmem @223 corumbxw OP 

# 32¢ msowsqq PatentApplication Publication

## Jul. 3, 2014 Sheet 4 0f 6 US 2014/0187802 A1 

## PatentApplication Publication



# w .wE A 

# |v $.sz A 

# cormbcwucouém 294 OF

393 UEQEO 226m

-23: Am



# 653 393 Al Eoi 

# 393 msowsc<


# corumbxm USU:

## Jul. 3, 2014 Sheet 5 0f 6 US 2014/0187802 A1 

## PatentApplication Publication



# : .sz

. 

# m wmmsm m30w36<0._.m 

# _wmmw> 

# cormbcwucou 294

.u a

# corwbcwucou Eu<



# cosuwbxm 80 .220



# 2260 @223

w 55.2mqu cwmoLPf .o_ 383g .m Eoi

## Jul. 3, 2014 Sheet 6 0f 6 US 2014/0187802 A1 

## PatentApplication Publication



# Eonmbcwucou Lou, 29$: A 393 2:220 wi?m 

# 5.53:5um U__>_U



# 8.53:5me

.0 282 :82, 225 .O_

w .wE 

# wmwgm UEQMLO

.m

# 8565852: 05233 EoI

## US 2014/0187802 A1

EFFICIENT, HIGH-YIELD CONVERSION OF SACCHARIDES IN A PURE OR CRUDE FORM 

### TO 5-(CHLOROMETHYL)-2-FURALDEHYDE

CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority as a continuation in 

### part ofPCT/US2013/057795, ?led 3 Sep. 2013; and to US. 

### provisional 61/818,418, ?led 1 May 2013; and to US. provi sional 61/714,225, ?led 16 Oct. 2012; each of which were 

### claimed for priority by PCT/US2013/057795. Each of the 

### foregoing is incorporatedhereinby reference. Background [0002] 5-(chloromethyl)-2-furaldehyde (CMF) is a furan based platform chemical derived from six carbon carbohy drates by the action ofconcentratedhydrochloric acid. CMF 

### has been the subject of numerous publications concerning both its formation frombiomass, as well as its use as a ?exible 

### platform molecule for creating specialty fuel and fuel prod ucts. While the chemistry ofproducing halogenated methyl furfurals had been examined (see, e.g., M. Mascal, Pat. 

### US007829732 B2, 2010) a production scale system for pro ducing CMF from saccharides in a pure or crude formhas not 

### yet been described. [0003] The formation of CMF from cellulosic and hemi cellulosic biomass (saccharides in a pure or crude form) also yields a by-product, which has been identi?ed as a precursor 

### to Hydrothermal Carbon (HTC), or Hydrothermal Carbon (HTC) itself. The size of HTC particles range from about 5

nm to about tens ofmicrometers (agglomerated) in diameter. 

### Whenproducing CMF, theseparticulates reside inbothaque ous and organic phases ofthe reactionmedium, making iso lation ofpure CMF di?icult. 

### [0004] A practical, but not production scale, continuous ?ow system forcreating CMFhasbeendescribedbyBrasholZ (see, e.g., M. BrasholZ, K. von Kanel, C. H. Homung, S. 

### Saubem and J. Tsanaktsidis, Green Chem., 2011, 13, 1114); however, this studydidnot address the scale andrepeatability limitations that prevent such a system from being utilized as
a production scale system. The system described in BrasholZ includes several limitations that are addressed in the present invention. [0005] Mascal in US 2009/0234142 describes a method of producing CMF. Mascal teaches a batch reaction, wherein polysaccharide and an aqueous acid are introduced to a reac 

### tionvessel, and then organic solvent is added continuously to the vest. Mascal accordingly teaches a method that allows continuous extraction of formed products from a batch reac tion. All ofMascal’s examples teach the batch reaction pro 

### ceeding for 30 hours, while reaction products are removed and organic solvent is added either continuously or at inter vals offrom 1 minute to 12 hours. Mascal teaches a single step ofcooling a reactionmixture forpreparing HMF from CMF. 

### Mascal, in an example of production of 5-methylfurfural, teaches the use of aqueous sodium bicarbonate to quench 

### previously added hydrochloric acid. Mascal’s methods 

## unavoidably produce 5-(hydroxymethyl)furfural (HMF), 2-(2-hydroxyacetyl)furan (HAF) and levulinic acid (LA) as 

### by products ofthe degradation ofCMF.

DESCRIPTION OF INVENTION [0006] The present invention describes methods and appa ratuses forthe synthesis ofCMF from saccharides in apure or 

### crude form. Examplemethods accordingto thepresent inven 

## Jul. 3, 2014

tion comprise: (a) contacting saccharides in a pure or crude 

### form, hydrochloric acid, and an organic solvent, by way ofa continuous, biphasic-?ow reactor assembly at a temperature from about 60 degree C. to about 200 degree C. andpressures from about 1 atm to 10 atm, such that CMF is produced; (b) 

## separating 5-(chloromethyl)-2-furaldehyde (CMF)byliquid/ liquidandsolid/liquidphase separation; (c)producingat least ?ve kilograms per day with at least 50% yield. 

### [0007] The present invention provides various advantages

over the prior art, including as an example the teaching of BrasholZ.As an example, the ?lter described in BrasholZwill 

### clog andbecome inoperable after approximately one hour of operation due to the formation of HydroThermal Carbon 

### (HTC) by-products on scales larger than described in their 

### invention. By immediately cooling thereactionmediumafter reaction by means of a heat remover as taught herein, HTC 

### formation is attenuated. As another example, following liq 

### uid/liquid extraction of the organic phase containing CMF from the aqueous acid phase, a washing ofthe organic phase with a basic aqueous solution, as taught herein, serves to 

### further enhance the yield ofCMF, and also reduces organic soluble HTC.

BRIEF DESCRIPTION OF THE DRAWINGS 

### [0008] The accompanying drawings, which are incorpo rated in and form part of the speci?cation, illustrate the 

### present inventionand, togetherwiththe description, describe the invention. [0009] FIG. 1 is a schematic illustration of a process 

### according to the present invention. [0010] FIG. 2 is a schematic illustration ofthe CMF forma tion phase ofthe process illustrated in FIG. 1. [0011] FIG. 3 is a schematic illustration ofthe Solid/Liquid 

### Separation phase ofthe process illustrated in FIG. 1. [0012] FIG. 4 is a schematic illustration of the Liquid/ 

### Liquid Separation phase ofthe process illustrated in FIG. 1. [0013] FIG. 5 is a schematic illustration of the Acid Con centration phase ofthe process illustrated in FIG. 1. [0014] FIG. 6 is a schematic illustration ofthe CMF Stabi lization phase ofthe process illustrated in FIG. 1.

MODES FOR CARRYING OUT THE INVENTION AND INDUSTRIAL APPLICABILITY 

### [0015] De?nitions [0016] In the description of the invention herein, various
terms are used as described below. Saccharides in a pure or crude formiThe term “saccharide” refers to a sugar, such as

a monosaccharide, a disaccharide, an oligosaccharide or a polysaccharide and any combinationthereof. “Saccharides in

a crude form” refers to monosaccharide based biomass, a disaccharide basedbiomass, an oligosaccharidebasedbiom

ass or a polysaccharide basedbiomass. Biomass is biological 

### material derived from living, or recently living organisms. It most often refers to plants or plant-derived materials which


### are speci?cally called lignocellulosic biomass. 

### [0017] Phase separationiDescribing separation of solid 

### from liquid by ?ltration through a semi-porous medium, by
way of gravity, vacuum, or mechanical force, such that the 

### solid is retained by the semi-porous medium; can describe 

### separation of liquid from liquid relying on differences in 

### density, by gravity or mechanical force, including the addi tion offresh solvent to remove furtherproduct from solution.

## US 2014/0187802 A1

[0018] Size exclusion separationiUsing a medium to separate solids from liquid based on solid particle size. 

### [0019] Continuous Flow4Comprises continuous provi sion ofallparts oftheprocess, that include, but not limitedto, 

### addition of starting materials, reaction itself, contact with heat removal devise, communication between parts of the 

### setup, phase separation, basewash, ?ltration, solvent remov 

### ing, and recovering chemicals, participating in the process. Practiced without substantial interruption or break, but not 

## necessarily constantly. [0020] Continuous ExtractioniDescribing a method of 

### separation either by liquid/liquid methods, or solid/liquid methods being practiced without substantial interruption or 

### break, but not necessarily constantly. [0021] Base Wash/basic washiUsing an inorganic base dissolved inwaterto treat CMF dissolved in anorganicphase, in order to neutralize or raise pH greater than or equal to 

### seven, and separating HTC from the organic phase. This will decrease CMF degradation under conditions of the reaction 

### and stabilize CMF in organic phase for further processing. This process is diagramed in FIG. 6. 

### [0022] BiphasiciHavingtwo distinctvisible liquidlayers, whichare immiscibledueto differences inpolarity, acidity, or density. In some cases two layers ofbiphasic system can be distinguished by the means ofproper device. 

### [0023] Hydrothermal Carbon (HTC)4Carbonaceous material agglomeratedunderhydro (water) thermal (elevated temperatures) conditions, which can be soluble under both 

### aqueous and organic environments. [0024] YieldiChemical yield of the product from the starting saccharides in a pure or crude form. The chemical yield canbeprovided inunits ofgrams ormoles, but is always based on the amount ofsaccharides in apure or crude forming the starting material and is used to determine the chemical 

### yield ofthe CMF. 

### [0025] While the chemistry ofproducing halogenated fur furals has been examined (see, e.g., M. Mascal, Pat., 

### US007829732 B2, 2010, incorporatedhereinbyreference), a production scale system for producing CMF from saccha rides in a pure or crude form has not yet been described. A 

### previously describedpractical, butnotproduction scale, con tinuous ?ow system creating CMF has been described (see, e.g., M. Brasholz, K. von Kanel, C. H. Hornung, S. Saubem 

### and J. Tsanaktsidis, Green Chem., 2011, 13, 1114, incorpo ratedhereinbyreference); however, this studydidnotaddress the scale and repeatability limitations that prevent such a system from being utilized as a production scale system. 

### [0026] First, the ?lter described in Brasholz will clog and become inoperable afterapproximately onehourofoperation dueto the formationofHTCby-products on scales largerthan 

### describedintheirinvention. By immediatelycoolingthereac tionmedium after reaction by means ofa heat remover, HTC 

### formation is attenuated. Second, following liquid/liquid extraction of the organic phase containing CMF from the aqueous acid phase, a washing of the organic phase with a basic aqueous solution serves to further enhance the yield of CMF, and also removes organic-soluble HTC. [0027] The present invention addresses these issues and provides the design and the process of a continuous ?ow, 

### biphasic reaction apparatus for ef?cient, high yield CMF production. CMFproduction includesamajor four-stagepro cess: contacting the reactants in a suitable environment, fol 

### lowed by ?ltration, phase separation and post production
treatment to prevent degradation, as was mentioned in [17]. 

## Jul. 3, 2014

As used herein, the term “yield” refers to the chemical yield oftheproduct from the starting saccharides in apure or crude form. The chemicalyield canbeprovided inunits ofgrams or moles, but is based on the amount of saccharides in a pure or crude forming the starting material and is used to determine 

### the chemical yield ofthe CMF and other furanic products. [0028] Inthe ?rst stage ofthisprocess, saccharides inapure 

### or crude form, hydrochloric acid, and an organic solvent (or mixture of solvents) are contacted by way of a continuous, biphasic-?ow reactor assembly at a temperature from about 60 degree C. to about 200 degree C. andpressures from about 

### 1 atmospheresto 20atmospheres, suchthatCMF isproduced. [0029] Saccharides in a pure or crude form suitable for this process include any six-carbon containing, ketose and aldose 

### isomers anddiastereomers ofglucose and fructose, including but not limited to mannose, glucose, galactose, sorbose, psi
cose, tagatose, allose, altrose, idose, andtalose, and any com bination thereof. These saccharides in a pure or crude form

can be in dry form, in paste form, or dissolved in a suitable solvent, such as water. [0030] Hydrochloric acid refers to aqueous solutions of 

### hydrogenchloridegas.Useful concentrations ofhydrochloric acid for the present invention are from 1% to 38%, or from 26% to 38%. In some embodiments, preferred concentrations

are from 30% to 36%. The hydrochloric acid useful in the present invention can contain inorganic salts, such as metal halides, lithium chloride or sodium chloride, as well as min 

### eral acids, including sulfuric acid and hydrobromic acid. [0031] Organic solvents refer to carrier ?uids which are immisciblewithwater. Organic solvents useful in thepresent invention include, but are not limited to, dichloromethane, 

### chloroform, carbon tetrachloride, diethyl ether, dipropyl ether, ethyl acetate, hexanes, dichloroethane and its isomers, trichloroethane and its isomers, toluene, benzene, and xylenes. Preferred organic solvents forthis invention include 

### those with densities greater than the hydrochloric acid, 

### including dichloromethane, chloroform, 1,2-dichloroethane, and other halogenated organic solvents and mixtures of sol vents useful for this process. 

### [0032] Temperatures useful in the present invention range from 60 degrees C. to 200 degrees C., preferably from 80 degrees C. to 120 degrees C. [0033] Pressures useful in thepresent inventionrange from 

### 1 atmosphere to 20 atmospheres, preferably from 1 atmo 

### spheres to 10 atmospheres. [0034] Reaction times useful for the present invention are from 1 second to 24 hours, preferably between 1 minute and 25 minutes, most preferably between 5 minutes and 15 min
utes. 

### [0035] In the present invention, the ?ow of organic and 

### aqueous phase liquids is continuous from exiting the pump until reachingthereceivingvessel. Used inthepresent inven tion the term “continuous” will be used as meaningpracticed without substantial interruption or break, but not necessarily 

## constantly. [0036] In orderto achievehighpressures and temperatures to allow for high ef?ciency conversion of saccharides in a pure or crude form to 5-(chloromethyl)-2-furaldehyde, the 

### organic phase and hydrochloric acid to be pressurized mechanicallyusingametered chemical delivery apparatus, or 

### similar device that is capable ofcreating pressures atvarying speed for a sustained amount oftime. 

### [0037] In the second stage of the process, the biphasic reactionmixture is constantly contacted with a heat remover

## US 2014/0187802 A1

device andis cooledtobetween 30 degrees C. to 40degrees C. Suitable heat exchange devices for this invention include ice 

### baths, heat sinks, and heat exchange pumps with coolant ?uid. Once cooled to between 30 degrees C. and 40 degrees 

### C., thebiphasic reactionmixture is continuously subjectedto 

### solid/liquid phase separation through a semi-porous mem brane, by the action ofvacuum, gravity, ormechanical force. 

### Semi-porous membranes useful inthis invention include, but

are not limited to, glass frit funnels, cellulose paper ?lters, 

### silica gel, alumina, sand, sock-type ?ltersmade out ofplastic 

### polymers (i.e.ipolyethylene, polypropylene, Te?on, etc.),

or combinations thereof. In this manner, insoluble HTC can be continuously removed and dried for disposal or use in 

### other applications. [0038] In the third stage ofthe process, liquid/liquidphase separation ofthe biphasic mixture can occur in a continuous, semi-continuous, or batch manner. At liquid/liquid phase 

### separation, theorganicphase containing CMF canbe concen trated to reduce total volume through simple distillation or
vacuumdistillation. Useful concentrations ofCMF in organic solvent are between 5 milligrams per milliliter to 1000 mil 

### ligrams per milliliter, preferably between 30 milligrams per milliliter to 500 milligrams per milliliter. [0039] The hydrochloric acid from this stage can be recon 

### centrated with dry hydrogen chloride gas and reused in sub sequent runs. HCl gas is communicated through the aqueous 

### phase liquid after being passed through above described apparatus so that the HCl content by mass is returned to at least 26% hydrochloric acid, to be used in conjunction or 

### separately to achieve desiredmolarity for CMF production. [0040] Inthe fourth stage oftheprocess, the organic phase, which contains organic-soluble or suspended in the organic phase HTC andresidualhydrochloric acid, iswashedwith an inorganic base dissolved in aqueous solution at or below the inorganic base’s solubility limit in water to create a state of pH greater than or equal to seven. This solution is used at a minimum of5%byvolume ofthe total volume ofthe organic 

### phase solution to wash the total volume of organic phase 

### containing the CMF product. Excess hydrochloric acid is neutralized in this manner, thus limiting degradation at room temperature of CMF and limiting further HTC formation. 

### [0041] Inorganic bases useful in the present invention include but are not limited to bicarbonate and carbonate salts 

### of alkali metals, including lithium, sodium, potassium, and cesium, andofalkalineearthmetals, suchas calcium,barium, magnesium, or combinations thereof. Concentrations ofinor ganic bases in aqueous solution useful in the present inven tion are from 0.1% to the respective solubility limit. 

### [0042] Material selection for apparatuses according to the present invention is important, since few materials are com patible with a mixture of a hydrochloric acid and organic solvents desired in the present invention. Suitable materials forthepresent inventionwhich include, but arenot limitedto, 

## Polypropylene, glass-?lled polypropylene, Polytetra?uoro ethylene (PTFE), Per?uoroalkoxy (PFA) resin, Fluorinated 

## ethylene propylene (FEP), Polyethylene, Polyvinylidene ?uoride (PVDF), Boro Silicate Glass,Viton ?uoroelastomer, Ethylene chlorotri?uoroethylene (Halar) coated steel or Tan talum infused steel. These materials must be taken into account at every interfacewith liquids describedhere, includ 

### ing, but not limited to, tanks, vessels, tubing/piping, valves, 

### pumps, ?ttings,unions,mixers,pressuredampeners, adapters

orbushings, inthat instancewhichbothhydrochloric acidand organic solvents arepresent,material selectionwould include 

## Jul. 3, 2014

but would not be limited to Polypropylene, glass-?lled 

### polypropylene, Polytetra?uoroethylene (PTFE), Per?uoro 

### alkoxy (PFA) resin, Fluorinated ethylene propylene (FEP), Polyethylene, Polyvinylidene ?uoride (PVDF), Boro Silicate 

### Glass, Viton ?uoroelastomer, Ethylene chlorotri?uoroethyl

ene (Halar) coated steel or Tantalum metal. 

### [0043] Phase separation includes liquid-gas, liquid-solid, gas-solid, liquid-liquid and solid-solid systems. The phase separation in this invention includes liquid-solid and liquid liquid. When CMF is produced by the method ofthis inven 

### tion, allphase separation is continuous because thematerials (either dry bulk or ?uids) that are being processed are con 

### tinuously inmotion. 

### [0044] Solid-liquid separationisamajorunitoperationthat exists in almost every ?ow scheme related to chemical pro cess industries. Depending on the properties of solid-liquid systems, various methods have beenused. Filtration and cen trifuge are the most commonly usedmethods inbatch, semi continuous and continuous modes. 

### [0045] Separation in liquid-liquid systems is most com monly accomplished by means of either gravity or a centri 

### fuge. A key difference is whether the droplets which consti tute the dispersed phase are large enough so that they rise or fall at a useful velocity. Liquid-liquid extraction, also known

as solvent extraction and partitioning, is amethod to separate compounds based on their relative solubility in two different 

### immiscible liquids, usually water (aqueous phase) and an organic solvent (organic phase). It is an extraction of a sub 

### stance from one liquidphase into another liquidphase.

EXAMPLE EMBODIMENTS 

### ExampleApparatus
[0046] FIG. 1 is a schematic illustration of an example 

### apparatus according to the present invention. A Reaction Vessel is provided, suitable to house a biphasic mixture, as 

### described above. The biphasic mixture continuously ?ows through the reactionVessel, where heat is added to it. From the reactor, the biphasic mixture which now contains CMF ?ows into a heat remover, where heat is removed from the 

### biphasic mixture, thereby reducing the formation rate of HTC. 

### [0047] A Solid/Liquid Separation system is in constant ?uid communicationwiththeheatremover, and con?guredto 

### continuouslyremove HTC createdduring CMFproduction in 

### the previous stages. A system con?gured to perform subse 

### quent washes of the material, fostering higher yields, is in constant ?uid communication with the Solid/Liquid Separa 

### tion system. The output ofthe subsequent washes comprises

an acidic aqueous phase, and an organic phase. The organic phase, which contains CMF for concentration is treated with

a basic solution to remove residual acid thereby preventing 

### CMF degradation. [0048] Additional information that can be useful in con 

### struction and operation ofembodiments ofthepresent inven tion canbe obtainedbyreview ofthe following, in connection 

### with the teaching ofthe present disclosure: M. Mascal, Pat., U5007829732 B2, 2010; M. BrasholZ, K. von Kanel, C. H. 

### Homung, S. SaubernandJ. Tsanaktsidis, GreenChem., 201 1, 

### 13, 1114; M. Mascal and E. B. Nikitin, Angew. Chem., Int. Ed., 2008, 47, 7924; M. Mascal and E. B. Nikitin, ChemSus Chem, 2009, 2, 859; M. Mascal and E. B. Nikitin, Green 

### Chem., 2010, 12, 370. Each ofthe preceding is incorporated by reference herein.

## US 2014/0187802 A1

[0049] An example method ofproduction according to the present invention provides a method for the production of CMF, in which saccharides in a pure or crude form, hydro 

### chloric acid, and an organic solvent (or mixture of organic solvents) are contactedbyway ofa continuous,biphasic-?ow reactor assembly at a temperature from about 60 degree C. to about 200 degree C. and pressures from about 1 atmosphere to 10 atmospheres, such that CMF is produced. 

### [0050] The steps ofan example method comprise: [0051] Saccharide, or saccharides in a pure or crude form,
are dissolved in hydrochloric acid, and at a set temperature and for a time, preferably two hours or less. 

### [0052] The acidic aqueous mixture and organic solvent (or mixture oforganic solvents) are then continuously contacted 

### together to form a biphasic mixture. Maintaining biphasic conditions in the reaction chamber is important to attainhigh yields. The term “biphasic” as usedhereinmeans having two 

### distinguishable layers, one being a low pH “aqueous phase” and the other being an “organic phase” containing the above 

### described organic solvent (or mixture of organic solvents) and any CMF created from the above reaction. [0053] The biphasic mixture is then heatedwith an oven or other thermal energy device, such as a microwave, allowing for saccharides in a pure or crude form conversion to CMF. [0054] To maintain the continuous biphasic ?ow, as described in theprevious step, thepressure canbemaintained suchthat theprocess temperature does not causevaporization ofthe reactants or the reaction media. Pressures useful in the present embodimentarebetween 8 atmospheres and 11 atmo 

## spheres. [0055] Aftera suitable reactiontime, the temperature ofthe biphasic mixture is then reduced, for example by means ofa heatremover, to slow theproductionofHydrothermal Carbon (HTC). A useful reaction time for this embodiment is two minutes. When an appropriate temperature is reached, the 

### biphasic mixture then continuously undergoes solid/liquid separation in order to remove HTC created during CMF pro duction. Useful temperatures for this embodiment for solid/ 

### liquid separation is between 30 degrees C. and 40 degrees C. [0056] The organic phase, which includes the CMF, canbe 

### separated continuously, semi-continuously, or in batches 

### responsive to the manufacturer’s preferences. Multiple sub sequent solvent washes can be used to recover more CMF 

### from the aqueous phase with an appropriate organic solvent which is immiscible with water. [0057] The acidic aqueous phase can then be ?ltered, and 

### thepH adjustedby the addition ofdryhydrogen chloride gas to so that optimal acid concentration can be achived, as described above. [0058] The organic phase can then be treated as described above in the de?nition sections as “base wash”.


### Example Embodiment and Operation for a 5 kg of 

### CMF/day system [0059] Fructose is fullydissolved in 32%hydrochloric acid at a ratio of 100g/L and aged for a minimum of 45 minutes. This mixture represents the aqueous phase ofthe reaction. 

### [0060] Dichloromethane represents the organic phase. The organicphase andaqueous phase liquids, either separately or combined, are interfaced at a “T” or “Y” type union using 

### 3/8" Per?uoroalkoxy (PFA) tubing in conjunction with PFA resin compression ?ttings. Here the biphasic interface is cre atedat aratio ofapproximately 1:1 (aqueousphaseto organic 

### phase). Upon converging at the biphasic interface, tubing, 

## Jul. 3, 2014

acting as the reactionvessel, is coiled and continuously used

as a biphasic-?ow reactor assembly in an oven (or heated in

some other way, such as having resistance heating wire near the tubing) such that the continuous ?ow resides in the oven 

### (oris otherwiseheated) forapproximately 2minutes orwhere in the biphasic mixture temperature reaches at least 100 

### degrees C. to allow for CMF production. Upon exiting the
oven, the tubing carrying the biphasic reaction mixture con tinuously enters a heat remover (e.g., a water bath type heat 

### remover) that allows for dissipation ofheat absorbed. Tem perature is allowed to drop to between 30 degrees C. and 40 degrees C. during this time.Apressure regulationdevice can be used as to regulate pressure in the reaction vessel, for example to maintain pressure greater than 70 PSI. [0061] HTC can then be removed by a sock type solid/ 

### liquid separation apparatus and the organic phase can be separatedby gravity, while the aqueous phase canbe ?ltered through a sock type ?lter, then communicated to a polyeth ylene tank,where HydrogenChloride gas canbebubbled into it bymeans ofaperforatedpolypropylene tube to concentrate 

### the acidto the original concentration (preferably 32% HClby weight), so that it is suitable for reuse in the system asAque
ous Phase material for CMF production. [0062] The base wash in this embodiment is done in the following manner: The organic phase is subjected to vacuum distillation until a concentration ofapproximately 300 milli
grams permilliliter ofCMF in DCM is reached. The concen trated CMF in DCM is washed at a 10:1 volume ratio of 

### organic phase to basic aqueous solution. The aqueous solu tion is madeby adding 100 g of sodium carbonate to 1.0 liter ofwater (0.94M) and the resulting aqueous solutionhas apH ofat least 7. Once the sodium carbonate is fully dissolved, the 

### basic wash media (washing solution) is ready for use. [0063] Previously, those skilled in the artwould expectthat

abasewashwoulddestroy CMF. However, the inventors have discovered that a basewash can remove aportion ofHTC and increase the yield of the reaction. HTC is comprised of two 

### components:polarandnon-polar (hydrophilicandhydropho bic). The base wash can make the hydrophilic component
morepolarandtherebyremove it into the aqueousphase. The 

### HTCparticles left in solvent-CMFphasepredominantly con tain hydrophobic moieties. It’s the HTC that contains the 

### polarmoieties thatreducethereactionyield; thehydrophobic type is a lot less reactive toward CMF. To convert CMF to other products, that HTC with polar moieties needs to be removed or else it will reduce the yield of subsequent reac tions substantially. There are other methods to separate the CMF from the dissolved HTC with the polar moieties, and they are lacking in their economic viability. If CMF is to be 

### separated from therest ofthe solventbydistillation, aportion 

### ofit will be destroyed by the polarportion ofthe remaining HTC. If CMF is to be separated from the remaining polar 

### HTCbyphysicalmethods, a largeproportionofthe CMFwill staybehind. IfCMF is to be convertedto anotherproduct, the 

### polarportion oftheremaining HTCwill deteriorate theyield ofthe desired reaction. The base wash describedherein over comes these limitation ofthe prior approaches.


### Example Embodiment for >100 kg CMF/Day 

### System
[0064] Another example embodiment ofthe current inven tion can be scaled for much larger amounts, with monosac 

### charide inputs totaling 100kg/day. This system canbe driven 

### by diaphragm-style pumps connected to polypropylene pip

## US 2014/0187802 A1

ing leading into HighDensity Polyethylene (HDPE)vessels.
A tantalum reaction vessel can be utilized for more effective heat transfer. In this embodiment utilizing continuous sepa ration and effective heat removal this embodiment would have the capability to be up scaled in?nitely. Continuous 

### separation discussed previously can be used, and Solid/Liq uid separation can be utilized during HTC removal prior to 

### Liquid/Liquid separationat aqueous and organicphase inter face during CMF production as well.

DETAILED DESCRIPTION OF THE DRAWINGS
[0065] FIG. 1 is a schematic illustration of a process according to thepresent invention.A CMF production step or 

### system feeds its output to a solid/liquid separation system. The solid output (HTC) is communicated to waterwash and 

### drying steps. The liquid output contains both the aqueous 

### phasewhich is acidic (the acidusedbeinghydrochloric acid) andthe organicphasewhichcontains thehalogenated solvent (methylene chloride in this embodiment) and CMF. This liq uid output is then communicated to a liquid/liquid step or 

### system. The aqueous output of the liquid/liquid Separation system (hydrochloric acid and a negligible amount of HTC impurities) is communicated to an acid concentration step or system,which inturn communicates concentratedacid, about 

### equal to the optimal acid concentration, back to the CMF Formation step or system. The chlorinated solvent output of the liquid/Liquid Separation system is communicated to a CMF Stabilization step or system (also referred to as the 

### “basewash”, as describedabove). The stabilized CMF is then concentrated by a simple distillation step or system, CMF may also be used as is in the form of a solution in an organic 

### solvent responsive to the manufacturer’s preferences. The chlorinated solvent is recovered from the distillation step and is communicated back to the CMF formation step. 

### [0066] CMF is created under biphasic (organic solvent/ aqueous) conditions in a reaction vessel, as in FIG. 2. Solid HTC is separated fromthe liquidmedia and communicatedto
a storage tank. Acidic aqueous phase is separated and 

### removed fromtheorganicphase. Theorganicphasedcontains 

### theproduct (CMF). The CMF intheorganicphaseundergoes stabilization as in FIG. 5. Aqueous phase is concentrated for

re-use in the systemat thebeginning ofthe CMF formation as in FIG. 5. [0067] FIG. 2 is a schematic illustration of the CMF For mation phase of the process illustrated in FIG. 1. Here the 

### acidic aqueous phase and the chlorinated solvent (methylene chloride in this embodiment) in the organic phase are com municated to a union where a biphasic condition is created. Once this biphasic ?ow enters the reaction vessel CMF and 

### HTC begin to form. Following the reaction vessel, the heat

remover then reduces the temperature ofthe reacted ?uid to 

### 30 degrees C.-40 degrees C. Biphasic ?ow is then continu ously communicatedto thephase separation step as shown in FIG. 3. [0068] A suitable reactionvessel can comprise coiled PFA tubing. A suitable heat remover can be a water bath type. 

### Separation can be completed mechanically or by gravity. Biphasic ?ow will exist from the organic phase and aqueous phase interface to the separation step. The aqueous phase can 

### comprise 32% HCl andmonosaccharaides at 100g/L aged for at least 45 minutes. The organic phase can comprise dichlo romethane. The reaction vessel can have a residence time of approximately 2minutes atapproximately 100C and 100 PSI. The heat remover can be capable of sustaining >100 PSI and 

## Jul. 3, 2014

100C under chemical conditions outlined above. Preferably temperature will be reduced >30C during the heat remover 

### step. [0069] FIG. 3 is a schematic illustration ofthe Solid/Liquid Separation phase of the process illustrated in FIG. 1. Here 

### continuous separation oftwo phases occurs: solid-liquid and 

## liquid-liquid. [0070] Each phase is communicated through the phase 

### separators. The separated solidphase andorganicphase (me thylene chloride in this embodiment) are proceeded for fur 

### therpuri?cation (FIG. 6). The aqueous phase (32% aqueous 

### HydrochloricAcid) is proceeded for extraction (FIG. 4). [0071] The solid/liquid and liquid/liquid are separated 

### through the phase separators. The separated solid phase and organic phase (heavy) are proceeded for further puri?cation

as in FIG. 6. The aqueous phase (light) is proceeded for extraction. [0072] FIG. 4 is a schematic illustration of the Liquid/ 

### Liquid Separation phase ofthe process illustrated in FIG. 1. 

### Aqueousphase fromphase separator (FIG. 3) and solventare mixed in a liquid-liquid extractor. The separated organic phase (in the case of a chlorinated organic solvent such as 

### methylene chloride in this embodiment) is proceeded for 

### furtherpuri?cation (FIG. 6). The aqueousphase isproceeded for acid re-concentration (FIG. 5). 

### [0073] Aqueous phase from phase separator (FIG. 3) and solvent are mixed in a liquid-liquid extractor. The separated 

### organic phase (heavy) are proceeded for further puri?cation 

### (FIG. 6). The aqueous phase (light) is proceeded for acid 

### re-concentration (FIG. 5). [0074] FIG. 5 is a schematic illustration ofthe acid concen trationphase oftheprocess illustrated inFIG. 1. The aqueous 

### phase from the separation step (FIG. 4) is communicated from a holding vessel to a concentration vessel that contains

a polypropylene diffuser or some method of communicating HCl gas into the aqueous phase so that the optimal molarity for the describedprocess is achieved. Following the concen tration step, the aqueous phase material will be suitable for



### reuse in the system starting at CMF formation (FIG. 2). 

### [0075] Hydrogen Chloride gas will be interfaced with aqueous phase via a diffusion type device. Acid Concentra tion vessel and diffuser canprovide above atmospheric pres 

### sure for sustained time.Aqueous phaseholding can comprise

avessel thatwillhold theprocessed andwashed acid. Hydro gen Chloride gas is communicated by means of tubing capable of tolerating its corrosive nature. An Acid Concen tration Vessel can house a polypropylene diffuser that will bubble the HCl gas through the used acid to return the acid to 

### its original concentration. [0076] FIG. 6 is a schematic illustration ofthe CMF Stabi lization phase ofthe process illustrated in FIG. 1. The stabi 

### lization vessel contains two phases, heavier organic phasei in the case ofa chlorinated organic solvent such asmethylene 

### chloride in this embodiment (containing CMF and solvent) and the lighterbase washmedia (washing solution described above). A two-layer interface, by means of a mixer or agita 

### tion, is allowed to settle andwill be separated gravitationally

or mechanically. The inventors have found that this step can be important to the stabilization and storage ofCMF and also

canremove some amount ofHTC beyondthe separation step. 

### [0077] Organic phase contains CMF and DCM solvent. Basic wash media contains 0.94 M sodium carbonate fully dissolved in water. The stabilization vessel can house a method ofmixing a and b.

## US 2014/0187802 A1

[0078] Thepresent inventionhas beendescribed in connec tion with various example embodiments. It will be under 

### stood that the above description is merely illustrative of the 

### applications of the principles of the present invention, the scope ofwhich is to be determined by the claims viewed in 

### light ofthe speci?cation. Othervariants andmodi?cations of the invention will be apparent to those skilled in the art.

We claim: 

### 1.Amethod forthe synthesis of5-(chloromethyl)-2-fural 

### dehyde (CMF) from saccharides, comprising contacting sac charides in a pure or crude form, hydrochloric acid, and an organic solvent ina continuous, biphasic-?ow reactor assem bly at a temperature from about 60 degrees C. to about 200 degrees C. and under pressure from about 1 atmospheres to 

### about 20 atmospheres.

2. A method as in claim 1, comprising continuously sup plying saccharides in apure or crude form, hydrochloric acid and an organic solvent into a biphasic-?ow reactor assembly, andwherein the residence time ofthe reaction is less than 60 minutes.

3.Amethodas in claim 1, further comprising continuously contacting the biphasic reaction output with a heat removal device after reaction is completed such that the output is cooled to 50 degrees C. or below in 5 minutes or less.

4. Amethod as in claim 1, further comprising washing the 

### cooled organic phase after continuous reaction in biphasic ?ow reactor assembly with an inorganic base dissolved in water to remove Hydrothermal Carbon (HTC) dissolved, or 

### suspended in the organic phase.

5. A method as in claim 1, wherein the method continu 

## ously synthesizes 5-(chloromethyl)-2-furaldehyde (CMF) with purity above 97%.

6.Amethodas in claim 2, further comprising continuously contacting the biphasic reaction output with a heat removal device after reaction is completed such that the output is cooled to 50 degrees C. or below in 5 minutes or less.

7. Amethod as in claim 2, further comprising washing the 

### cooled organic phase after continuous reaction in biphasic ?ow reactor assembly with an inorganic base dissolved in water to remove Hydrothermal Carbon (HTC) dissolved, or 

### suspended in the organic phase.

8. A method as in claim 2, wherein the method continu 

## ously synthesizes 5-(chloromethyl)-2-furaldehyde (CMF) with purity above 97%.

9. Amethod as in claim 3, further comprising washing the 

### cooled organic phase after continuous reaction in biphasic ?ow reactor assembly with an inorganic base dissolved in water to remove Hydrothermal Carbon (HTC) dissolved, or 

### suspended in the organic phase.

10. A method as in claim 3, wherein the method continu 

## ously synthesizes 5-(chloromethyl)-2-furaldehyde (CMF) with purity above 97%. 11. A method as in claim 4, wherein the method continu 

## ously synthesizes 5-(chloromethyl)-2-furaldehyde (CMF) with purity above 97%. 12. An apparatus for the synthesis of CMF from saccha rides in pure or crude form, comprising a biphasici?ow 

## Jul. 3, 2014

reactor assembly con?gured to accommodate continuous contacting ofsaccharides inpure or crude form, hydrochloric acid, and an organic solvent at a temperature from about 60 degrees C. to about 200 degrees C. andpressures from about 

### 1 atmospheres to about 20 atmospheres.

13. A method as in claim 1, wherein the concentration of 

### hydrochloric acid is from 1% to 38% byweight, andwherein thehydrochloric acid contains one ormoreof: inorganic salts, 

### lithium chloride, sodium chloride, mineral acids, sulfuric 

### acid, andhydrobromic acid.

14. A method as in claim 1, wherein the organic solvent 

### comprises dichloromethane, chloroform, carbon tetrachlo 

### ride, diethyl ether, dipropyl ether, ethyl acetate, hexanes, dichloroethane and its isomers, trichloroethane and its iso 

### mers, toluene, benzene, xylenes, andmixtures thereof.

15. A method as in claim 3, wherein the heat removal devices comprises one ormore of: icebath, heat sink, andheat 

### exchange pump with coolant ?uid.

16. A method as in claim 1, wherein the biphasic reaction 

### mixture is subjected to solid/liquidphase separation through

a semi-porousmembrane, by the action ofvacuum, gravity, or mechanical force. The semi-porousmembrane comprises one 

### ofmore of: glass frit funnel, cellulose paper ?lter, silica gel, 

### alumina, sand, plastic polymer sock-type ?lter, polypropy lene sock-type ?lter and PTFE sock-type ?lter.

17. A method as in claim 1, in which insoluble HTC and 

### HTC dissolved or suspended in the organic phase is removed 

### and dried by way of solid/liquid phase separation. The organicphase containing CMF is concentratedto reduce total volume by distillation or distillation to a concentration in organic solventofbetweenabout 5milligramspermilliliterto about 1000 milligrams per milliliter.

18. A method as in claim 1, wherein the organic phase is washed with an inorganic base dissolved in aqueous solution at or below the inorganic base’s solubility limit in water to create a state ofpH not less than seven. The aqueous solution ofan inorganic base is used at a minimum of 5% by volume ofthe total volume ofthe organic phase solution to wash the 

### total volume oforganic phase.

19. A method as in claim 18, wherein the inorganic base comprises one ormore of: (a)bicarbonate, (b) carbonate salts of alkali metals including one or more of lithium, sodium, 

### potassium, and cesium;

and (c) alkaline earth metals including one or more of



### calcium,barium,magnesium.Theconcentrationofinor ganic bases in aqueous solution is from 0.1% to the 

### respective solubility limit. 20. An apparatus as in claim 12, wherein the reactor is made ofone ormore of: Polypropylene, glass-?lledpolypro 

## pylene, Polytetra?uoroethylene (PTFE), Per?uoroalkoxy (PFA) resin, Fluorinated ethylenepropylene (PEP), Polyeth ylene, Polyvinylidene ?uoride (PVDF), Boro Silicate Glass
or, Viton ?uoroelastomer, Tantalum metal and Tantalum infused steel. Every part of the apparatus that is in contact with the reaction is made of one of more of the materials mentioned above.