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 (l,4)-α-D-glucan, while amylopectin is a branched, bushlike structure containing both (l,4)-α-D linkages between D-glucose residues and (l,6)-α-D branch points, Ullmann 's Encyclopedia of Industrial Chemistry, Vol. A25, 1994, p. 1-18. Following formulae depict representative structures of amylose and amylopectin.

Representative structure of linear amylose

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

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 μm. Rice starch has the smallest granules (3-9 μm), potato starch ranges between 15-100 μm and corn starch granules are 5-26 μm with an average diameter of 15 μm. Additionally, wheat starch granules are typically from 3 to 35 μm and corresponding barley starch from 5 to 35 μm. Kirk-Othmer, Encyclopedia of Chemical Technology, 1997, 4th edition, Vol. 22, p. 699-719 and Ketola H, Andersson T, Papermaking Chemistry, 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 maximum, and then decreases asymptotically 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 ⁰ C, Ullmann 's Encyclopedia of Industrial Chemistry, Vol. A26, 1995, p. 246-248.

The effect of thermal treatment 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

the predominant reaction during extrusion, Kirk-Othmer, Encyclopedia of Chemical Technology, 1997, 4th edition, Vol. 22, p. 699-719.

Dissolution of starch

US 1 943 176 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 form 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 Example 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 improvement 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 l-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.

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 ⁰ C to 200 ⁰ C, but this might even exceed 300 ⁰ 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 thermal stabilities. Typically, these solvents are organic salts or mixtures 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 fme-tuning for specific applications. Furthermore, 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 summary 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 (CR. Strauss; "A

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 at. published in 2002 a method for dissolution of pure cellulose fibers into ionic liquids in the microwave field (Swatloski, R.P.; Spear S.K.; Holbrey, J.D.; Rogers, R.D. Journal of American Chemical Society, 2002, 124, p. 4974-4975). Furthermore, 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 formed 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 temperatures 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 comprising mixing 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

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 more preferably between 1.5 MPa and 2.0 MPa.

The dissolution of the starch can be carried out at a temperature between O ⁰ C and 15O ⁰ C, preferably at a temperature between 1O ⁰ C and 100 ⁰ C, such as between 2O ⁰ C and 85 ⁰ C. If microwave irradiation is applied, the heating can be carried out be means of this irradiation. The solution is agitated until complete 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 amount 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 ⁰ C and 200 ⁰ C ₅ preferably at a temperarure of below 17O ⁰ C, and more preferably between -50 ⁰ C and 120 ⁰ 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:

Pyridinium Pyridazinium Pyrimidinium Pyrazinium

Imidazolium Pyrazolium Oxazolium

Quinolinium Isoquinolinium

Piperidinium Pyrrolidinium wherein R ¹ and R ² are independently a C ₁ -C ₆ alkyl or C ₂ -C ₆ alkoxyalkyl group, and R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and R ⁹ are independently hydrogen, a C ₁ -C ₆ alkyl, C ₂ -C ₆ alkoxyalkyl or C ₁ -C ₆ alkoxy group or halogen.

In the above formulae R ¹ and R ² are preferably both Ci -C ₄ alkyl, and R ³ -R ⁹ , when present, are preferably hydrogen.

C ₁ -C ₆ alkyl includes methyl, ethyl, propyl, iso-propyl, butyl, sec-butyl, tert-butyl, pentyl, the isomers of pentyl, hexyl and the isomers of hexyl.

C ₁ -C ₆ alkoxy contains the above C ₁ -C ₆ alkyl bonded to an oxygen atom.

C ₂ -C ₆ 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:

O

Oxazolium

wherein R » 1 - τR>5 are as defined above.

An especially preferred cation is the imidazolium cation having the formula: - wherein R*-R ⁵ are as defined above. In this formula R ³ -R ⁵ are preferably each hydrogen and R ¹ and R ² are independently C ₁ -C ₆ alkyl or C ₂ -C ₆ alkoxyalkyl. More preferably one of R ¹ and R ² is methyl and the other is C ₁ -C ₆ alkyl. In this formula R ³ 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;

C ₁ -C ₆ carboxylate such as formate, acetate, propionate, butyrate, lactate, pyruvate, maleate, fumarate or oxalate;

nitrate;

C ₂ -C ₆ carboxylate substituted by one or more halogen atoms such as trifluoroacetic acid;

C ₁ -C ₆ alkyl sulfonate substituted by one or more halogen atoms such as trifluoromethane sulfonate (triflate);

tetrafluoroborate BF ₄ ^" ; or

phosphorus hexafluoride PF ₆ ^" .

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 C ₁ -C ₆ carboxylate. The halogen is preferably chloride, bromide or iodide, and the pseudohalogen is preferably thiocyanate or cyanate.

If the cation is a l-(CrC ₆ -alkyl)-3-methyl-imidazolium, the anion is preferably a halogenid, especially chloride.

A preferred ionic liquid solvent is l-butyl-3-methyl-imidazolium chloride (BMIMCl) having a melting point of about 60 ⁰ 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

wherein R ¹⁰ , R ¹¹ , R ¹² and R ¹³ are independently a C ₁ -C ₃₀ alkyl, C ₃ -C ₈ carbocyclic or C ₃ -C ₈ heterocyclic group, and the anion is halogen, pseudohalogen, perchlorate, C ₁ - C ₆ carboxylate or hydroxide.

The C ₁ -C ₃₀ alkyl group can be linear or branched and is preferably a C ₁ -C ₁₂ alkyl group.

The C ₃ -C ₈ carbocyclic group includes cycloalkyl, cycloalkenyl, phenyl, benzyl and phenylethyl groups.

The C ₃ -C ₈ 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-isopropylethyleamine), TMEDA (N, N, N', N')-tetramethylethylenedianamine etc. The other organic bases are not omitted. Typically, organic bases are rather expensive reagents. Thus, organic bases

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 C ₁ -C ₆ alkyl, aryl or aryl C ₁ -C ₃ alkyl group 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.

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 C ₁ -C ₉ alkyl, aryl and aryl C ₁ -C ₃ alkyl.

The aryl group includes phenyl and naphthyl.

The aryl C ₁ -C ₃ alkyl group (also called aralkyl) is an aryl group as defined above bond to the O group of the cellulose by means of an alkyl group containing 1, 2 or 3 carbon atoms. The aryl C ₁ -C ₃ 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 dicarboxymethylcelmlose

- 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 (CeIl-OH stands for cellulose):

a) Starch-OH + R _a -X + MOH *- Starch-O-R _a

b) Starch-OH +

Starch-O-CH-CH-R _b

ZH

c) Starch-OH + R _d -CH=C(Y)R _e + MOH »- Starch-O-CH-CH-Y

Re d) Starch-OH + R _r CHN ₂ + MOH ► Starch-O-CH ₂ R _f

In the above reaction schemes:

M is Li, Na or K,

X is halogen, such as chloride, bromide or iodide, or sulfate,

R _a is C ₁ -C ₆ alkyl, aryl or aryl C ₁ -C ₃ 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,

R _a can also be silyl substituted by three groups selected from the group consisting of C ₁ -C ₉ alkyl, aryl and aryl C ₁ -C ₃ alkyl,

Z is O (the cyclic compound being an epoxide) or NH (the cyclic compound being an aziridine),

R _b and R _c are independently hydrogen or C ₁ -C ₃ 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,

Y is an electron-attracting substituent, such as cyano (CN), amide (CONH ₂ ) or sulfo (SO ₃ -Na ⁺ ),

R _d and R _e are independently hydrogen or C ₁ -C ₃ alkyl, and

R _f is Ci-C ₅ alkyl.

The aryl and aryl C ₁ -C ₃ alkyl groups are as defined above.

The alkoxy group is preferably C ₁ -C ₆ alkyl-O-.

When preparing starch silyl ethers the reactant R _a -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 C ₁ -C ₆ 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

• 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 (BMIMCl, 5g, melting point 6O ⁰ 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 7O ⁰ 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 ⁰ C and analysed with FTIR. The obtained spectrum for carboxymethylcellulose is shown in Fig. 1 [1630 cm-ly _as (COO ^' ), 1424 cm-1 v _s (COO ^' )]. The product dissolves readily in water.