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 IN A PURE OR CRUDE FORM 1, 2013, provisional application No. 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?tlolgg i: ;(US)_ The present invention describes methods and apparatuses for 

Edward Nikiti’n Aug u; u’e NM ’ the synthesis of 5-(chloromethyl)-2-furaldehyde (CMF) from _ ’ . q q . ’ saccharides in pure 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 ?ve kilograms per day With at least 

(22) Flled' Man 3’ 2014 50% yield. Embodiments of the present invention can pro 

. . duce CMF in a continuous fashion, With high yield and With 

Related U's' Apphcatlon Data out degradation of CMF to such side products as 5-(hy 

(63) Continuation-in-part of application No. PCT/U S2013/ droxymethy1)furfura1 (HMF), 2-(2-hydroxyacety1)furan 

057795, ?led on Sep. 3, 2013. (HAF) and levulinic acid (LA). 
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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 of PCT/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 incorporated herein by reference. Background 

[0002] 5-(chloromethyl)-2-furaldehyde (CMF) is a furan 

based platform chemical derived from six carbon carbohy 

drates by the action of concentrated hydrochloric acid. CMF 

has been the subject of numerous publications concerning 

both its formation from biomass, as well as its use as a ?exible 

platform molecule for creating specialty fuel and fuel prod 

ucts. While the chemistry of producing 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 form has 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 of micrometers (agglomerated) in diameter. 

When producing CMF, these particulates reside in both aque 

ous and organic phases of the reaction medium, making iso 

lation of pure CMF di?icult. 

[0004] A practical, but not production scale, continuous 

?ow system for creating CMF has been described by BrasholZ 

(see, e.g., M. BrasholZ, K. von Kanel, C. H. Homung, S. 

Saubem and J. Tsanaktsidis, Green Chem., 2011, 13, 1114); 

however, this study did not address the scale and repeatability 

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 

tion vessel, 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 of Mascal’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 of from 1 minute to 12 hours. Mascal teaches a single step 

of cooling a reaction mixture for preparing 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 of the degradation of CMF. 

DESCRIPTION OF INVENTION 

[0006] The present invention describes methods and appa 

ratuses for the synthesis of CMF from saccharides in a pure or 

crude form. Example methods according to the present inven 

Jul. 3, 2014 

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

form, hydrochloric acid, and an organic solvent, by way of a 

continuous, biphasic-?ow reactor assembly at a temperature 

from about 60 degree C. to about 200 degree C. and pressures 

from about 1 atm to 10 atm, such that CMF is produced; (b) 

separating 5-(chloromethyl)-2-furaldehyde (CMF) by liquid/ 

liquid and solid/ liquid phase separation; (c) producing at 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 BrasholZ will 

clog and become 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 the reaction medium after 

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 of the organic phase 

with a basic aqueous solution, as taught herein, serves to 

further enhance the yield of CMF, 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 invention and, together with the 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 of the CMF forma 

tion phase of the process illustrated in FIG. 1. 

[0011] FIG. 3 is a schematic illustration of the Solid/Liquid 

Separation phase of the process illustrated in FIG. 1. 

[0012] FIG. 4 is a schematic illustration of the Liquid/ 

Liquid Separation phase of the process illustrated in FIG. 1. 

[0013] FIG. 5 is a schematic illustration of the Acid Con 

centration phase of the process illustrated in FIG. 1. 

[0014] FIG. 6 is a schematic illustration of the CMF Stabi 

lization phase of the 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 combination thereof. “Saccharides in 

a crude form” refers to monosaccharide based biomass, a 

disaccharide based biomass, an oligosaccharide based biom 

ass or a polysaccharide based biomass. 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 of fresh solvent to remove further product 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 of all parts of the process, that include, but not limited to, 

addition of starting materials, reaction itself, contact with 

heat removal devise, communication between parts of the 

setup, phase separation, base wash, ?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 in water to treat CMF dissolved in an organic phase, 

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] BiphasiciHaving two distinct visible liquid layers, 

which are immiscible due to differences in polarity, acidity, or 

density. In some cases two layers of biphasic system can be 

distinguished by the means of proper device. 

[0023] Hydrothermal Carbon (HTC)4Carbonaceous 

material agglomerated under hydro (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 can be provided in units of grams or moles, but is always 

based on the amount of saccharides in a pure or crude forming 

the starting material and is used to determine the chemical 

yield of the CMF. 

[0025] While the chemistry of producing halogenated fur 

furals has been examined (see, e.g., M. Mascal, Pat., 

US007829732 B2, 2010, incorporated herein by reference), a 

production scale system for producing CMF from saccha 

rides in a pure or crude form has not yet been described. A 

previously described practical, but not production 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 

rated herein by reference); however, this study did not address 

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 after approximately one hour of operation 

due to the formation of HTC by-products on scales larger than 

described in their invention. By immediately cooling the reac 

tion medium after reaction by means of a 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. CMF production includes a major four-stage pro 

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 

of the product from the starting saccharides in a pure or crude 

form. The chemical yield can be provided in units of grams 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 of the CMF and other furanic products. 

[0028] In the ?rst stage of this process, saccharides in a pure 

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. and pressures from about 

1 atmospheres to 20 atmospheres, such that CMF is produced. 

[0029] Saccharides in a pure or crude form suitable for this 

process include any six-carbon containing, ketose and aldose 

isomers and diastereomers of glucose and fructose, including 

but not limited to mannose, glucose, galactose, sorbose, psi 

cose, tagatose, allose, altrose, idose, and talose, 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 

hydrogen chloride gas. Useful concentrations of hydrochloric 

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 

immiscible with water. Organic solvents useful in the present 

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 for this 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 the present invention range 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 reaching the receiving vessel. Used in the present inven 

tion the term “continuous” will be used as meaning practiced 

without substantial interruption or break, but not necessarily 

constantly. 

[0036] In order to achieve high pressures 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 

mechanically using a metered chemical delivery apparatus, or 

similar device that is capable of creating pressures at varying 

speed for a sustained amount of time. 

[0037] In the second stage of the process, the biphasic 

reaction mixture is constantly contacted with a heat remover 
US 2014/0187802 A1 

device and is cooled to between 30 degrees C. to 40 degrees 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., the biphasic reaction mixture is continuously subjected to 

solid/liquid phase separation through a semi-porous mem 

brane, by the action of vacuum, gravity, or mechanical force. 

Semi-porous membranes useful in this invention include, but 

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

silica gel, alumina, sand, sock-type ?lters made out of plastic 

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 of the process, liquid/liquid phase 

separation of the biphasic mixture can occur in a continuous, 

semi-continuous, or batch manner. At liquid/liquid phase 

separation, the organic phase containing CMF can be concen 

trated to reduce total volume through simple distillation or 

vacuum distillation. Useful concentrations of CMF 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 desired molarity for CMF production. 

[0040] In the fourth stage of the process, the organic phase, 

which contains organic-soluble or suspended in the organic 

phase HTC and residual hydrochloric acid, 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 of 

pH greater than or equal to seven. This solution is used at a 

minimum of 5% by volume of the total volume of the 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, and of alkaline earth metals, such as calcium, barium, 

magnesium, or combinations thereof. Concentrations of inor 

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 

for the present invention which include, but are not limited to, 

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 interface with liquids described here, includ 

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

pumps, ?ttings, unions, mixers, pressure dampeners, adapters or bushings, in that instance which both hydrochloric acid and 

organic solvents are present, material selection would 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 of this inven 

tion, all phase separation is continuous because the materials 

(either dry bulk or ?uids) that are being processed are con 

tinuously in motion. 

[0044] Solid-liquid separation is a major unit operation that 

exists in almost every ?ow scheme related to chemical pro 

cess industries. Depending on the properties of solid-liquid 

systems, various methods have been used. Filtration and cen 

trifuge are the most commonly used methods in batch, 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 a method 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 liquid phase into another liquid phase. 

EXAMPLE EMBODIMENTS 

Example Apparatus 

[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 reaction Vessel, 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 communication with the heat remover, and con?gured to 

continuously remove HTC created during CMF production 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 of the 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 of embodiments of the present inven 

tion can be obtained by review of the following, in connection 

with the teaching of the present disclosure: M. Mascal, Pat., 

U5007829732 B2, 2010; M. BrasholZ, K. von Kanel, C. H. 

Homung, S. Saubern and J. Tsanaktsidis, Green Chem., 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 of the preceding is incorporated 

by reference herein. 
US 2014/0187802 A1 

[0049] An example method of production 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 contacted by way of a 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 of an 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 of organic solvents) are then continuously contacted 

together to form a biphasic mixture. Maintaining biphasic 

conditions in the reaction chamber is important to attain high 

yields. The term “biphasic” as used herein means 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 heated with 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 the previous step, the pres sure can be maintained 

such that the process temperature does not cause vaporization 

of the reactants or the reaction media. Pressures useful in the 

present embodiment are between 8 atmospheres and 11 atmo 

spheres. 

[0055] After a suitable reaction time, the temperature of the 

biphasic mixture is then reduced, for example by means of a 

heat remover, to slow the production of Hydrothermal 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, can be 

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 

the pH adjusted by the addition of dry hydrogen 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 fully dissolved in 32% hydrochloric acid 

at a ratio of 100g/L and aged for a minimum of 45 minutes. 

This mixture represents the aqueous phase of the reaction. 

[0060] Dichloromethane represents the organic phase. The 

organic phase and aqueous 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 

ated at a ratio of approximately 1:1 (aqueous phase to organic 

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

Jul. 3, 2014 

acting as the reaction vessel, 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 

(or is otherwise heated) for approximately 2 minutes or where 

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 of heat absorbed. Tem 

perature is allowed to drop to between 30 degrees C. and 40 

degrees C. during this time. A pressure regulation device 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 

separated by gravity, while the aqueous phase can be ?ltered 

through a sock type ?lter, then communicated to a polyeth 

ylene tank, where Hydrogen Chloride gas can be bubbled into 

it by means of a perforated polypropylene tube to concentrate 

the acid to the original concentration (preferably 32% HCl by 

weight), so that it is suitable for reuse in the system as Aque 

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 of approximately 300 milli 

grams per milliliter of CMF 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 made by adding 100 g of sodium carbonate to 1.0 liter 

of water (0.94M) and the resulting aqueous solution has a pH 

of at 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 art would expect that 

a base wash would destroy CMF. However, the inventors have 

discovered that a base wash can remove a portion of HTC and 

increase the yield of the reaction. HTC is comprised of two 

components: polar and non-polar (hydrophilic and hydropho 

bic). The base wash can make the hydrophilic component 

more polar and thereby remove it into the aqueous phase. The 

HTC particles left in solvent-CMF phase predominantly con 

tain hydrophobic moieties. It’s the HTC that contains the 

polar moieties that reduce the reaction yield; the hydrophobic 

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 the rest of the solvent by distillation, a portion 

of it will be destroyed by the polar portion of the remaining 

HTC. If CMF is to be separated from the remaining polar 

HTC by physical methods, a large proportion of the CMF will 

stay behind. If CMF is to be converted to another product, the 

polar portion of the remaining HTC will deteriorate the yield 

of the desired reaction. The base wash described herein over 

comes these limitation of the prior approaches. 

Example Embodiment for >100 kg CMF/Day 

System 

[0064] Another example embodiment of the current inven 

tion can be scaled for much larger amounts, with monosac 

charide inputs totaling 100 kg/day. This system can be driven 

by diaphragm-style pumps connected to polypropylene pip 
US 2014/0187802 A1 

ing leading into High Density 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 separation at aqueous and organic phase inter 

face during CMF production as well. 

DETAILED DESCRIPTION OF THE DRAWINGS 

[0065] FIG. 1 is a schematic illustration of a process 

according to the present invention. A CMF production step or 

system feeds its output to a solid/liquid separation system. 

The solid output (HTC) is communicated to water wash and 

drying steps. The liquid output contains both the aqueous 

phase which is acidic (the acid used being hydrochloric acid) 

and the organic phase which contains the halogenated 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 in turn communicates concentrated acid, 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 

“base wash”, as described above). 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 from the liquid media and communicated to 

a storage tank. Acidic aqueous phase is separated and 

removed from the organic phase. The organic phased contains 

the product (CMF). The CMF in the organic phase undergoes 

stabilization as in FIG. 5. Aqueous phase is concentrated for 

re-use in the system at the beginning of the 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 of the reacted ?uid to 

30 degrees C.-40 degrees C. Biphasic ?ow is then continu 

ously communicated to the phase separation step as shown in 

FIG. 3. 

[0068] A suitable reaction vessel 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 and monosaccharaides at 100 g/L aged for 

at least 45 minutes. The organic phase can comprise dichlo 

romethane. The reaction vessel can have a residence time of 

approximately 2 minutes at approximately 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 of the Solid/Liquid 

Separation phase of the process illustrated in FIG. 1. Here 

continuous separation of two phases occurs: solid-liquid and 

liquid-liquid. 

[0070] Each phase is communicated through the phase 

separators. The separated solid phase and organic phase (me 

thylene chloride in this embodiment) are proceeded for fur 

ther puri?cation (FIG. 6). The aqueous phase (32% aqueous 

Hydrochloric Acid) 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 of the process illustrated in FIG. 1. 

Aqueous phase from phase separator (FIG. 3) and solvent are 

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 

further puri?cation (FIG. 6). The aqueous phase is proceeded 

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 of the acid concen 

tration phase of the process illustrated in FIG. 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 described process 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 can provide above atmospheric pres 

sure for sustained time. Aqueous phase holding can comprise 

a vessel that will hold the processed and washed 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 of the CMF Stabi 

lization phase of the process illustrated in FIG. 1. The stabi 

lization vessel contains two phases, heavier organic phasei 

in the case of a chlorinated organic solvent such as methylene 

chloride in this embodiment (containing CMF and solvent) 

and the lighter base wash media (washing solution described 

above). A two-layer interface, by means of a mixer or agita 

tion, is allowed to settle and will be separated gravitationally 

or mechanically. The inventors have found that this step can 

be important to the stabilization and storage of CMF and also 

can remove some amount of HTC beyond the 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 of mixing a and b. 
US 2014/0187802 A1 

[0078] The present invention has been described 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 of which is to be determined by the claims viewed in 

light of the speci?cation. Other variants and modi?cations of 

the invention will be apparent to those skilled in the art. 

We claim: 

1. A method for the synthesis of 5-(chloromethyl)-2-fural 

dehyde (CMF) from saccharides, comprising contacting sac 

charides in a pure or crude form, hydrochloric acid, and an 

organic solvent in a 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 a pure or crude form, hydrochloric acid 

and an organic solvent into a biphasic-?ow reactor assembly, 

and wherein the residence time of the reaction is less than 60 

minutes. 

3. A method as 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. A method 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. A method as 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. A method 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. A method 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 of saccharides in pure or crude form, hydrochloric 

acid, and an organic solvent at a temperature from about 60 

degrees C. to about 200 degrees C. and pressures 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% by weight, and wherein 

the hydrochloric acid contains one or more of: inorganic salts, 

lithium chloride, sodium chloride, mineral acids, sulfuric 

acid, and hydrobromic 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, and mixtures thereof. 

15. A method as in claim 3, wherein the heat removal 

devices comprises one or more of: ice bath, heat sink, and heat 

exchange pump with coolant ?uid. 

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

mixture is subjected to solid/ liquid phase separation through 

a semi-porous membrane, by the action of vacuum, gravity, or 

mechanical force. The semi-porous membrane comprises one 

of more 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 

organic phase containing CMF is concentrated to reduce total 

volume by distillation or distillation to a concentration in 

organic solvent of between about 5 milligrams per milliliter to 

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 of pH not less than seven. The aqueous solution 

of an inorganic base is used at a minimum of 5% by volume 

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

total volume of organic phase. 

19. A method as in claim 18, wherein the inorganic base 

comprises one or more 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. The concentration of inor 

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 of one or more of: Polypropylene, glass-?lled polypro 

pylene, Polytetra?uoroethylene (PTFE), Per?uoroalkoxy 

(PFA) resin, Fluorinated ethylene propylene (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.