Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
Starch etherification method
Field of the invention
The present invention is directed to a new method for preparing starch ethers.
Background art
Unlike other carbohydrates and edible polymers, starch occurs as discrete
particles
called starch granules. These are generally composed of two type of molecules,
amylose and amylopectin. Of these, amylose is a linear (1,4)-a-D-glucan, while
amylopectin is a branched, bushlike structure containing both (1,4)-a-D
linkages
between D-glucose residues and (1,6)-a-D branch points, Ullmann 's
Encyclopedia
of Industrial Chemistry, Vol. A25, 1994, p. 1-18. Following formulae depict
representative structures of amylose and amylopectin.
CH2OH CH2OH CH2OH
O O
OH OH OHO
-O O O O
OH OH OH
Representative structure of linear amylose
CH2OH CH2OH
O O
OH OH
O O O
OH 01
CHZOH CH2 CHaOH
O O
OH OH
-O O O OHO
O
OH OH OH
Representative structure of amylopectin, including (1,6)-a-branch point
Normal starches contain approximately 75% amylopectin molecules the rest
consisting of amylose. Amylopectin is a very large molecule with molecular
masses
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
2
ranging from one to several millions. Linearly structured amylose is
considerably
smaller and the molecular masses usually fall in the range of 5000 - 200000.
Commercial starches are obtained from seeds, particularly corn, wheat, rice,
tapioca
arrowroot, sago, and potato. Especially in Scandinavia, also barley is
utilized as a
native starch source. Among these, the starch granules vary in diameter from
1-100 m. Rice starch has the smallest granules (3-9 m), potato starch ranges
between 15-100 in and corn starch granules are 5-26 in with an average
diameter
of 15 in. Additionally, wheat starch granules are typically from 3 to 35 m
and
corresponding barley starch from 5 to 35 m. Kirk-Othmer, Encyclopedia of
Chemical Technology, 1997, 4th edition, Vol. 22, p. 699-719 and Ketola H,
Andersson T, Papermaking Chemistr.y, 1999, Book 4, p. 269-274.
Due to their extremely high molecular masses as well as chemical composition
consisting of both amylose and especially bushlike amylopectin, these branched
polysaccharides are practically insoluble into other solvents than water. And
in
water, the starch granules must be cooked before they will release their water-
soluble molecules. In general, they do not form true solutions in water
because of
their molecular sizes and intermolecular interactions; rather they form
molecular
dispersions. Most starch derivatives can be prepared from any native starch
but, for
reasons of solublity and molecular size, they are mainly produced from potato
starch and, in the United States, from waxy maize starch.
Above a certain temperature, characteristic for each type of starch and known
as
gelatinization temperature, the starch grains burst and form a gel. The
viscositity
increases to a maximuin, and then decreases asyinptotically to a limiting
value as
the solubilized polymer molecules in water disperse. Complete solubilization
of
individual molecules of a starch grain only occurs above 100 C, Ullmann's
Encyclopedia of IndustNial Chemistry, Vol. A26, 1995, p. 246-248.
The effect of thermal treatinent on starches depends strongly on whether it
occurs in
excess water, limited water, under pressure, or in extrusion cooking. In
excess water
it appears that starch swelling is a two-stage process consisting of initial
granule
swelling followed then by granule dissolution. Both of these steps are
irreversible.
In limited water, thermal responses have been interpreted as being due to
starch
crystallite melting. When extrusion cooking is applied, starch granules are
torn
physically apart, allowing thus more rapid penetration of water into the
granule. In
contrast to normal gelatinization, starch fragmentation (dextrinization)
appears to be
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
3
the predominant reaction during extrusion, Kirk-Othmer, Encyclopedia of
Chemical
Technology, 1997, 4th edition, Vol. 22, p. 699-719.
Dissolution of starch
US 1943 176 discloses a process for the preparation of solutions of cellulose
by
dissolving cellulose under heating in a liquefied N-alkylpyridinium or N-
benzyl-
pyridinium chloride salt, preferably in the presence of an anhydrous nitrogen-
containing base, such as pyridine. These salts are known as ionic liquids. The
cellulose to be dissolved is preferably in the fonn of regenerated cellulose
or
bleached cellulose or linter. US 1 943 176 also suggests separating cellulose
from
the cellulose solution by means of suitable precipitating agents, such as
water or
alcohol to produce for example cellulose threads or films or masses. According
to
US 1 943 176 the cellulose solutions are suitable for various chemical
reactions,
such as etherification or esterification. In Exainple 14
triphenylchloromethane is
added to a solution of cellulose in a mixture of benzylpyridinium chloride and
pyridine, and subsequently the cellulose solution is poured into methylalcohol
to
separate the cellulose ether.
Also other cellulose solvents are known. For example, viscose rayon is
prepared
from cellulose xanthate utilizing carbon disulfide as both reagent and
solvent.
US 3 447 939 discloses dissolving natural or synthetic polymeric compounds,
such
as cellulose in a cyclic mono(N-methylamine-N-oxide), especially N-methyl-
morpholine-N-oxide.
WO 03/029329 discloses a dissolution method very similar to the one disclosed
in
US 1 943 176. The main iinproveinent resides in the application of microwave
radiation to assist in dissolution. The cellulose to be dissolved is fibrous
cellulose,
wood pulp, linters, cotton balls or paper, i.e. cellulose in a highly pure
form. The
inventors of WO 03/029329 have published an article (Swatloski, R.P.; Spear
S.K.;
Holbrey, J.D.; Rogers, R.D. Journal of American Chemical Society, 2002, 124,
p.
4974-4975) focussed on the dissolution of cellulose with ionic liquids,
especially
1-butyl-3-methyl-imidazolium chloride, by heating in a microwave oven. The
cellulose used in the dissolution experiments was dissolving pulp (from
cellulose
acetate, lyocell, and rayon production lines), fibrous cellulose and filter
paper, i.e.
cellulose in a highly pure form that does not contain any significant amounts
of
lignin. This article also teaches precipitating cellulose from the ionic
liquid solution
by the addition of water or other precipitating solutions including ethanol
and
acetone.
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
4
Ionic liquids
The literature knows many synonyms used for ionic liquids. Up to date, "molten
salts" is maybe the most broadly applied term for ionic compounds in the
liquid
state. There is a difference between molten salts and ionic liquids, however.
Ionic
liquids are salts that are liquid around room temperature (typically -100 C to
200 C,
but this might even exceed 300 C) (Wassercheid, P.; Welton, T., Ionic Liquids
in
Synthesis 2003, WILEY-VCH, p. 1-6, 41-55 and 68-81). Therefore, the term RTIL
(room temperature ionic liquids) is commonly applied for these solvents.
RTILs are non-flammable, non-volatile and they possess high therinal
stabilities.
Typically, these solvents are organic salts or inixtures consisting of at
least one
organic component. By changing the nature of the ions present in an RTIL, it
is
possible to change the resulting properties of the RTILs. The lipophilicity of
an
ionic liquid of a RTIL is easily modified by the degree of cation
substitution.
Similarly, the miscibility with water and other protic solvents can be tuned
from
complete miscibility to almost total immiscibility, by changing the anion
substitution.
All these variations in cations and anions can produce a very large range of
ionic
liquids allowing the fine-tuning for specific applications. Furthennore, the
RTILs
are relatively cheap and easy to manufacture. They can also be reused after
regeneration.
Microwaves
It is known from the recent literature concerning organic synthesis that the
reaction
times of the organic reactions are remarkable reduced when the energy
necessary
for the occurrence of the reaction is introduced to the system by using
microwave
irradiation. The commonly used frequency for microwave energy is 2.45 GHz.
There is a wide and continuously increasing literature available in the area
of using
microwave techniques in organic synthesis. An example of a short sununary
article
of this topic was published by Mingos in 1994 (D. Michael P. Mingos;
"Microwaves
in chemical synthesis" in Chemistry and industry 1. August 1994, pp. 596-599).
Loupy et. al. have recently published a review concerning heterogenous
catalysis
under microwave irradiation (Loupy, A., Petit, A., Hamelin, J., Texier-
Boullet, F.,
Jachault, P., Mathe, D.; "New solvent-free organic synthesis using focused
microwave" in Synthesis 1998, pp. 1213-1234). Another representative article
of
the area is published by Strauss as an invited review article (C.R. Strauss;
"A
CA 02621974 2008-03-07
WO 2007/006848 PCT/FI2006/000248
combinatorial approach to the development of Environmentaly Benign Organic
Chemical Preparations", Aust. J Chem. 1999, 52, p. 83-96).
Because of their ionic nature, ionic liquids are excellent media for utilizing
microwave techniques. Rogers et al. published in 2002 a method for dissolution
of
5 pure cellulose fibers into ionic liquids in the microwave field (Swatloski,
R.P.;
Spear S.K.; Holbrey, J.D.; Rogers, R.D. Journal of Arnerican Chemical Society,
2002, 124, p. 4974-4975). Furthennore, they were able to precipitate the
fibers
back by mixing this fiber-containing solution with water.
Summary of the invention
It is an object of this invention to provide a method for preparing starch
ethers.
The invention is based on the surprising discovery that alkaline
etherification of
starch can be conducted in an ionic liquid wherein the reaction between
cellulose
and the etherifying agent, such as chloroacetic acid/ alkali metal
chloroacetate
proceeded fast and smoothly and no solubility problems of reagents or the
product
fonned were detected. The good solubility of reagents accomplishes efficient
and
economic reactions without any unnecessary excess of the inorganic base, such
as
NaOH, thus preventing also the cellulose chain degradation. The possibility
for the
severe degradation is further diminished by the mild reaction conditions and
low
reaction teinperatures achieved either by microwave irradiation or by
pressure.
Due to good solubility of all the starting materials, the invention also
accomplishes
the possibility to easily control the DS via the reagent to AGU [anhydro-
glucopyranose unit(s)] molar ratio. The invention also accomplishes the
possibility
to prepare highly or fully substituted cellulose ethers and due to better
solubility,
mild conditions and shorter reaction times, also a method to produce
completely
new kind of cellulose ethers. The ionic liquids can be reused after
regeneration.
Brief description of the drawings
In the enclosed drawing Fig. 1 shows a spectrum obtained by FTIR analysis of a
carboxymethyl starch sample prepared by the method of the present invention.
Detailed description of the invention
According to the invention there is provided a method for preparing a starch
ether
coinprising inixing starch with an ionic liquid solvent to dissolve the
starch, and
then treating the dissolved starch with an etherifying agent in the presence
of a base
CA 02621974 2008-03-07
WO 2007/006848 PCT/FI2006/000248
6
to form a starch ether, and subsequently separating the starch ether from the
solution, wherein both the dissolution and the etherification are carried out
in the
substantial absence of water.
The dissolution and etherification can be assisted by applying microwave
irradiation
and/or pressure.
The pressure is preferably at most 2.0 MPa and inore preferably between 1.5
MPa
and 2.0 MPa.
The dissolution of the starch can be carried out at a temperature between 0 C
and
150 C, preferably at a temperature between 10 C and 100 C, such as between 20
C
and 85 C. If microwave irradiation is applied, the heating can be carried out
be
means of this irradiation. The solution is agitated until coinplete
dissolution is
obtained.
In the dissolution, no auxiliary organic solvents or co-solvents, such as
nitrogen-
containing bases, e.g. pyridine, are necessary. Organic bases are excluded in
this
manner.
The dissolution and the etherification are carried out in the substantial
absence of
water. The phrase "in the substantial absence of water" means that not more
than a
few percent by weight of water is present. Preferably, the water content is
less than
1 percent by weight.
The starch can be present in the solution in an ainount of about 1% to about
35% by
weight of the solution. Preferably the amount is from about 10% to about 25%
by
weight.
The etherification can be carried out at the same temperature as the
dissolution or at
a lower temperature. Both inorganic and organic base can be applied as
catalysts.
The ionic liquid solvent is molten at a temperature between -100 C and 200 C,
preferably at a temperarure of below 170 C, and more preferably between -50 C
and 120 C.
The cation of the ionic liquid solvent in preferably a five- or six-membered
heterocylic ring optionally being fused with a benzene ring and comprising as
heteroatoms one or more nitrogen, oxygen or sulfur atoms. The heterocyclic
ring
can be aromatic or saturated. The cation can be one of the following:
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
7
Rq R4 R4
R3 R5 R3 R5 R3 R3 N Rq
N
R7 O Rs Rs ON Rs N~~ R5 Rs ONK Rs
R' R' R1
R~
Pyridinium Pyridazinium Pyrimidinium Pyrazinium
Rq R5 R3 Rq R5 R3
Rl ~N(~DhN ,R2 RZ N'0 R5 R" N~JO
R Rl R"
Imidazolium Pyrazolium Oxazolium
Rq R3 Rq R3 R3 R2 Rs~/R3
~ ~~
R~.N,~,N.Ra R~N,N N R~.~O~Rq R NU5
R2 Y
1,2,3-Triazolium 1,2,4-Triazolium
Thiazolium
R5 R4 R4 R3
Rs R3 R5 R9
R7 N R9 Rs N,Rl
R8 Rl R7 R8
Quinolinium Isoquinolinium
R4
R3 R5 R5 R4
R~ .N, R6 Rs R3
R~+ RZ
Piperidinium Pyrrolidinium
wherein R' and R2 are independently a C1-C6 alkyl or C2-C6 alkoxyalkyl group,
and
R3, R4, R5, R6, R7, R8 and R9 are independently hydrogen, a C1-C6 alkyl, C2-C6
alkoxyalkyl or C1-C6 alkoxy group or halogen.
In the above fornlulae R' and R2 are preferably both C1-C4 alkyl, and R3-R9,
when
present, are preferably hydrogen.
C1-C6 alkyl includes methyl, ethyl, propyl, iso-propyl, butyl, sec-butyl, tert-
butyl,
pentyl, the isomers of pentyl, hexyl and the isomers of hexyl.
C1-C6 alkoxy contains the above C1-C6 alkyl bonded to an oxygen atom.
C2-C6 alkoxyalkyl is an alkyl group substituted by an alkoxy group, the total
number of carbon atoms being from two to six.
Halogen is preferably chloro, bromo or fluoro, especially chloro.
Preferred cations have following formulae:
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
8
R4 R5 R3 R4 R5 R3
,=N'- i~~ 2 R2.N0 5 R1=NUO
R
R3 R N R R1 R4
Imidazolium Pyrazolium Oxazolium
R4 R3 R4 R3 R3 R2 R5~ R3
,~
~v''~
~.N,ON. 2 ~.N + R~=~D~R4 R1
R N R R N N
R2 R4
1,2,3-Triazolium 1,2,4-Triazolium Thiazolium
wherein R1-R5 are as defined above.
An especially preferred cation is the imidazolium cation having the formula:
R4 R5
1~' 2
R Y R
R3
wherein R1-R5 are as defined above. In this fonnula R3-R5 are preferably each
hydrogen and R' and R2 are independently C1-C6 alkyl or C2-C6 alkoxyalkyl.
More
preferably one of R' and R2 is methyl and the other is C1-C6 alkyl. In this
formula
R3 can also be halogen, preferably chloro.
The anion of the ionic liquid solvent can be one of the following:
halogen such as chloride, bromide or iodide;
pseudohalogen such as thiocyanate or cyanate;
perchlorate;
C1-C6 carboxylate such as formate, acetate, propionate, butyrate, lactate,
pyruvate,
maleate, fumarate or oxalate;
nitrate;
C2-C6 carboxylate substituted by one or more halogen atoms such as
trifluoroacetic
acid;
C1-C6 alkyl sulfonate substituted by one or more halogen atoms such as
trifluoromethane sulfonate (triflate);
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
9
tetrafluoroborate BF4 ; or
phosphorus hexafluoride PF6-.
The above halogen substituents are preferably fluoro.
The anion of the ionic liquid solvent is preferably selected among those
providing a
hydrophilic ionic liquid solvent. Such anions include halogen, pseudohalogen
or
C1-C6 carboxylate. The halogen is preferably chloride, bromide or iodide, and
the
pseudohalogen is preferably thiocyanate or cyanate.
If the cation is a 1-(C1-C6-alkyl)-3-methyl-imidazolium, the anion is
preferably a
halogenid, especially chloride.
A preferred ionic liquid solvent is 1-butyl-3-methyl-imidazolium chloride
(BMIMCI) having a melting point of about 60 C.
Another type of ionic liquid solvents useful in the present invention is an
ionic
liquid solvent wherein the cation is a quaternary ammonium salt having the
formula
R11
R1o_N+ R12
R13
wherein Rlo, R", R12 and R13 are independently a C1-C30 alkyl, C3-C8
carbocyclic or
C3-C8 heterocyclic group, and the anion is halogen, pseudohalogen,
perchlorate, Cl-
C6 carboxylate or hydroxide.
The C1-C30 alkyl group can be linear or branched and is preferably a C1-C12
alkyl
group.
The C3-C8 carbocyclic group includes cycloalkyl, cycloalkenyl, phenyl, benzyl
and
phenylethyl groups.
The C3-C8 heterocyclic group can be aromatic or saturated and contains one or
more
heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur.
The inorganic base used in the etherification is preferably an alkali metal
hydroxide
such as litium, sodium or potassium hydroxide. Typical organic bases include
such
basic catalysts as TEA (triethylamine), DIPEA (di-isopropylethyleainine),
TMEDA
(N, N, N', N')-tetramethylethylenedianamine etc. The other organic bases are
not
omitted. Typically, organic bases are rather expensive reagents. Thus, organic
bases
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
are employed as catalysts and in catalytic volumes, i.e. they are not employed
in
equimolar or excess volumes.
The ether group of the starch ethers prepared by the method of the present
invention
can be a C1-C6 alkyl, aryl or aryl C1-C3 alkyl group optionally substituted by
one or
5 more functional groups selected from the group consisting of carboxyl,
hydroxyl,
amino, alkoxy, halogen, cyano, amide, sulfo, phosphoro, nitro and silyl.
The ether group of the starch ethers prepared by the method of the present
invention
can also be a silyl group substituted by three similar or different groups
selected
from the group consisting of C1-C9 alkyl, aryl and aryl C1-C3 alkyl.
10 The aryl group includes phenyl and naphthyl.
The aryl C1-C3 alkyl group (also called aralkyl) is an aryl group as defined
above
bond to the 0 group of the cellulose by means of an alkyl group containing 1,
2 or 3
carbon atoms. The aryl C1-C3 alkyl group includes for example benzyl,
diphenylmethyl, trityl and phenylethyl.
Typical cellulose ethers prepared by the method of the present invention
include:
- alkylated sta
- 2-hydroxyethylcellulose, 2-hydroxypropylcellulose and 2-butylethylcellulose
- 2-aminoethylcellulose
- 2-cyanoethylcellulose
- carboxymethylcellulose, 2-carboxyethylcellulose and dicarboxymethylcellulose
- 2-sulfoethylcellulose
- 2-phosphoromethylcellulose.
Typical cellulose silyl ethers prepared by the method of the present invention
include: trimethylsilylcellulose, tert-butyldimethylsilylcellulose,
diphenylmethyl-
silylcellulose, triphenylsilylcellulose, tribenzylsilylcellulose, thexyl-
dimethylsilyl-
cellulose and triisopropylsilylcellulose.
According to the present invention the cellulose ethers can be prepared by any
of
following four reactions (Cell-OH stands for cellulose):
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
11
a) Starch-OH + Ra-X+ MOH Starch-O-Ra
Rc
b) Starch-OH + \7-Rb
+ MOH
Z
Rc
I
Starch-O-CH-CH-Rb
I
ZH
Rd
I
c) Starch-OH + Rd-CH=C(Y)Re + MOH 0 Starch-O-CH-CH-Y
Re
d) Starch-OH + Rt-CHN2 + MOH 10 Starch-O-CH2Rf
In the above reaction schemes:
M is Li, Na or K,
X is halogen, such as chloride, bromide or iodide, or sulfate,
Ra is C1-C6 alkyl, aryl or aryl C1-C3 alkyl, said alkyl or aryl optionally
being
substituted by one or more functional groups selected from the group
consisting of
carboxyl, hydroxyl, amino, alkoxy, halogen, cyano, amide, sulfo, phosphoro,
nitro
and silyl,
Ra can also be silyl substituted by three groups selected from the group
consisting of
C1-C9 alkyl, aryl and aryl C1-C3 alkyl,
Z is O(the cyclic compound being an epoxide) or NH (the cyclic coinpound being
an aziridine),
Rb and Rc are independently hydrogen or C1-C3 alkyl optionally substituted by
one
or more functional groups selected from the group consisting of carboxyl,
hydroxyl,
amino, alkoxy, halogen, cyano, amide, sulfo, phosphoro, nitro and silyl,
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
12
Y is an electron-attracting substituent, such as cyano (CN), amide (CONH2) or
sulfo
(SO3-Na+),
Rd and Re are independently hydrogen or C1-C3 alkyl, and
Rf is C1-C5 alkyl.
The aryl and aryl C1-C3 alkyl groups are as defined above.
The alkoxy group is preferably C1-C6 alkyl-O-.
When preparing starch silyl ethers the reactant Ra-X is preferably a silyl
chloride.
According to the present invention both single-substituted starch ethers
having only
one kind of substituent, and mixed cellulose ethers having two or more
different
substituents can be prepared.
After the etherification the obtained starch ether can be separated from the
solution
by adding a non-solvent for the starch ether to precipitate the starch ether.
The non-
solvent should also be a non-solvent for the ionic liquid solvent and miscible
with
the ionic liquid solvent. Said non-solvent is preferably an alcohol, such as a
C1-C6
alkanol, for example methanol, ethanol, propanol or isopropanol. Also other
non-
solvents, such as ketones (e.g. acetone), acetonitrile, dichloromethane,
polyglycols
and ethers can be used. With appropriate DS of the starch ether, even water
can be
employed as a non-solvent.
It is also possible to separate the obtained starch ether by extraction with a
suitable
solvent that is a non-solvent for the ionic liquid solvent.
The main advantages of preferred methods of the present invention for the
preparation of starch ethers in ionic liquids are as follows:
= excellent solubility of the reagents used
= due to good solubility, possibility to employ all native starches in
derivative
prepararation
= excess of reagents, which in turn would result in starch chain degradation,
is
avoided
= fast and economical preparation of starch ethers
= fast and economical separation of reaction products by precipitating the
prepared product by adding a non-solvent for the product, and further, a
simple, energy efficient drying procedure of the products
CA 02621974 2008-03-07
WO 2007/006848 PCT/F12006/000248
13
= preparation of existing and also new starch ether products
= dramatically shorter reaction times and lower reaction temperatures by use
of
microwave irradiation and/or pressure
= mild reaction conditions
= easy control of the degree of substitution (DS) via the molar ratio of
reagent
to anhydroglucopyranose unit(s) (AGU)
= possibility to prepare highly or fully substituted (DS = 3) starch ethers
= possibility to prepare mixed ethers
= possibility to reuse the ionic liquids
The percentages in this specification refer to % by weight unless otherwise
specified.
Example
Carboxymethylation of starch
500 mg of starch was dissolved into an ionic liquid (BMIMCI, 5g, melting point
60 C) with the aid of microwaves, resulting in 10% solution. Addition of
monochloroacetic acid (2.05 eqv.) was followed by addition of slight excess of
solid
NaOH (3.25 eqv.). The reaction was conducted at 70 C for two hours, the
product
being subsequently precipitated by adding isopropanol into the reaction
mixture.
The precipitate was filtered off and the by-product salts were removed by
washing
the precipitate with isopropanol. The washed product carboxymethylated starch
was
dried overnight in oven at 105 C and analysed with FTIR. The obtained spectrum
for carboxymethylcellulose is shown in Fig. 1 [1630 cm-1 vas(COO-), 1424 cm-1
vs
(COO-)]. The product dissolves readily in water.
