WO2006010470A1 - Method for production of polysaccharides and polysaccharide derivatives comprising aminoalkyl groups - Google Patents

Abstract

The invention relates to a method for production of polysaccharides and polysaccharide derivatives comprising aminoalkyl groups whereby a) a polysaccharide or polysaccharide derivative is dispersed in a mixture of a water-miscible aprotic solvent and water, b) the polysaccharide or polysaccharide derivative is basified with an inorganic base, c) during the basification the amount of water used is adjusted to between 1 and 55 mol water per anhydroglycose unit of the polysaccharide or polysaccharide derivative, d) an amination with an etherification reagent is carried out optionally at increased temperature, e) optional neutralisation and f) the reaction product is filtered off, washed and, optionally, dried and milled. The invention further relates to polysaccharide derivatives, comprising aminoalkyl groups produced thus, with a given degree of total substitution.

Description

Process for the preparation of aminoalkyl-containing polysaccharides and polysaccharide derivatives

The invention relates to a process for the preparation of aminoalkyl-containing polysaccharides and polysaccharide derivatives by etherification of free hydroxyl groups of polysaccharides or polysaccharide derivatives and the aminoethyl polysaccharides or Polysaccharid¬ derivatives themselves.

Chitosan, 2-amino-2-deoxy-cellulose, is the only cationic polysaccharide that can be used in large quantities. It is used, inter alia, as an acid-stable thickener in cosmetic preparations, as a paper auxiliaries and as a chelating agent and flocculant. The extraction of this natural polysaccharide, however, is a complex process, which is reflected in high prices of the products. The high price has hitherto hindered the widespread use of chitosan.

Previously known processes for the preparation of amino group-containing polysaccharides or polysaccharide derivatives have the disadvantage that only a small portion of the amination reagents used is bound to the polysaccharide or polysaccharide derivative. Therefore, a corre sponding excess of these reagents must be used in order to achieve high degrees of substitution (US Pat. No. 2,623,042).

In DE-A 1 946 722 it is proposed to use cellulose or cellulose derivatives with small amounts of organic solvents in a kneader, e.g. react with diethylaminoethyl chloride. Kneaders consist of e.g. from a doppelmuldenfδrmigen kneading chamber in which two mutually stripping kneading blades rotate and cover almost the entire kneading space.

Overall, high compressive, tensile and shear forces and thus strong friction prevail in the kneaded by an alternate approach and removal of the blade surfaces to and from each other. Due to the high stress of the polysaccharide due to the high compressive, tensile and shear forces, undesired chain degradation can occur. Kneaders are characterized by high investment costs, based on the small reactor volume. In contrast, stirred tanks or reaction mixers with a capacity of a few 10 m ^{3 are} relatively inexpensive to produce.

The handling of highly viscous, optionally tacky reaction mixtures, which is associated with the process described in DE-A 1 946 722, is problematical since these sometimes sticky materials can not be pumped or pneumatically conveyed. The cleaning of the compacted mass is also difficult because the washing liquid can not easily penetrate into the interior of the compacted mass. The object of the present invention was therefore to provide an economical process which allows aminoalkyl-containing polysaccharides and derivatives

With a high yield, based on the etherification reagent (with etherifying reagent is meant here the reagent for the transfer of the aminoalkyl group (amination))

In inexpensive, widely used aggregates such as e.g. Stirred reactors and reaction mixers

manufacture.

The invention therefore provides a process for the preparation of aminoalkylgruppenhaltiger polysaccharides and polysaccharide derivatives, characterized in that

a) dispersing a polysaccharide or polysaccharide derivative in a mixture of a water-miscible aprotic solvent and water, and

b) the polysaccharide or polysaccharide derivative alkalized with an inorganic base and

c) during the alkalization the amount of water used in the range between 1 and 55 moles of water per Anhydroglycoseeinheit the polysaccharide or polysaccharide derivative sets and

d) subsequently carrying out an amination with an etherifying reagent at optionally elevated temperature and then

e) optionally neutralized and

f) the reaction product is filtered off, washed, optionally dried and ground.

Surprisingly, higher yields can be achieved without increased technical complexity in simple stirred reactors with a solvent system consisting of a water-miscible aprotic solvent and water in certain proportions than in other known to the expert protic or water-immiscible solvents and solvent mixtures. The yield is calculated according to the formula mentioned in EP-A 0 310 787:

Yield (in%) = DS ^ _r. / DS _acc .

theoretically possible DS, is calculated from the molar ratio of

Etherifying reagent to anhydro sugar

DS _acc. = measured DS, calculated from the formula

U n _δEEM . - -% N 'M _PS mzt

⁸ (14.10O) - ( ⁰ ZoN - (M ₇₆ -I))

Molecular weight fraction of a monomer unit of the polysaccharide or

Polysaccharide derivatives in g / mol

% N = measured nitrogen value in% by weight, based on dry product

Mve ⁼ molecular weight of the etherifying reagent in g / mol

Thus, at a nitrogen content of 5.35 wt .-% for a Diisopropylaminoethylcel- lulose

_{DS =} 5.36% * 162.14g / mol _{= 1 2L}

(14 g / mol «100%) - (5.35% • (127.24 g / mol)) '

However, this formula gives only exact values if the nitrogen content refers only to the amino group-containing polysaccharide. However, the values stated after the nitrogen determination (according to Kjeldahl) refer to the total mass, optionally corrected for the moisture. A more accurate DS _gem . is calculated if the nitrogen value is related to the active content, ie the measured nitrogen content is corrected by the acids and salts still present:

DS _acc .

with Ag = active content, based on the total dry matter in%

For the purposes of this invention, a water-miscible aprotic solvent in admixture with water in the ratio used according to the invention during the reaction shows no phase separation at room temperature. The water-miscible used according to the invention Aprotic solvents have no hydroxyl or amino groups which can react with the etherification reagent.

Preferred water-miscible aprotic solvents are open-chain or cyclic ethers of the general formula

R ₃ -OR _b -R ₀ .

In this formula mean

R ₃ and R _{0 are} independently branched, linear or cyclic alkyl radical or aryl radical having 1 to 24 carbon atoms, preferably R ₄ = R ₀ = methyl or ethyl and

R _b = (C _n H _2n O) _n , where n = 2-4 and m = 0-3.

Cyclic ethers, e.g. Dioxane, can also be used.

Particularly preferred ethers are cyclic or open chain ethers having 2-10 carbon atoms and 1-3 oxygen atoms, most preferably the ether is non-cyclic, especially dimethoxyethane is used. Non-water-miscible ethers, e.g. Diethyl ether or methyl tert-butyl ether are not suitable.

In a further preferred embodiment, open-chain or cyclic compounds of the type R ₃ SO ₂ R _c , for example tetrahydrothiophene-1, 1-dioxide (sulfolane) are used.

Polysaccharides are preferably natural polysaccharides obtained from plants or microorganisms or their constituents, such as e.g. Dextran, pullulan, starch, and cellulose. Preferably, cellulose is used. Polysaccharides containing carboxylic acid or sulfonic acid groups, e.g. Xylans, xanthan gum and carrageenan can also be used.

Polysaccharide derivatives are derivatives of polysaccharides, in particular hydroxyethyl, hydroxypropyl, methyl and ethyl polysaccharides and polysaccharides mixed with these substituents. Particularly preferred are methyl cellulose, hydroxyethyl cellulose, methyl hydroxyethyl cellulose, ethyl cellulose, ethyl hydroxyethyl cellulose, hydroxypropyl cellulose, methyl hydroxypropyl cellulose and ethyl hydroxypropyl cellulose. The total degree of substitution of these derivatives, if it is a cellulose ether, is preferably between 0.1 and 4, more preferably between 0.5 and 3. The average degree of substitution of alkyl substituents (DS _A i _k yi) is between 0 and 2, 5 particularly preferably between 0 and 1.7. The molar degree of substitution of hydroxyalkyl substituents (MS _H yd _r o _x y _a i _k yi) is between 0 and 3.5, more preferably between 0 and 2.5. The polysaccharide derivative used is preferably a water-insoluble cellulose ether or a cellulose ether having a thermal flocculation point in water.

Suitable etherifying agents are compounds of the general formula

X- (CH ₂ VNR ₁ R ₂

in which

X is a leaving group, preferably chlorine, bromine, iodine or a sulfonic acid residue R'SO ₃ , where R 'is an aromatic or aliphatic radical having 1 to 24 C atoms, for example para-toluyl or methyl,

X is preferably chlorine and

n must be at least 2

the radicals Ri and R ₂ independently of one another are aliphatic or branched or cyclic, where appropriate heteroatom-substituted alkyl or aryl substituents or H. Two radicals R 1 and R ₂ can form a ring together with the nitrogen.

Ri and R ₂ independently contain 1 to 24 C atoms.

Examples of etherifying reagents to be used according to the invention are N-2-chloroethyldiisopropylamine, N-2-chloroethyldiethylamine, N-3-chloropropyldiethylamine, N-2-chloroethyldimethylamine and N-2-chloropropyldimethylamine , The radicals R 1 and R ₂ can form a cyclic radical together with the nitrogen. Examples of etherifying reagents used according to the invention, in which two radicals R 1 and R ₂ form a ring together with the nitrogen, are N-2-chloroethylpyrrolidine, N-2-chloroethylpiperidine and N-2-chloroethylmorpholine. The etherification reagents can be used in the form of the ammonium salts, for example preferably of a hydrochloride. Both the solid and a solution of, for example, 65% or 50% by weight in water or other solvent may be used.

Preference is given to using N-2-chloroethyldiisopropylamine hydrochloride and N-2-chloroethyldiethylamine hydrochloride.

About 0.1-3 mol, preferably about 0.3-2 mol, more preferably about 1-2 mol of etherification reagent are used per mol of anhydroglucose, if cellulose is used as starting material. When a cellulose derivative is used, 0.01 to 1.5 mol, preferably 0.1 to 1 mol, particularly preferably 0.1 to 0.8 mol of etherifying reagent per mol of anhydroglucose are sufficient.

The polysaccharide or polysaccharide derivative is preferably stirred with an inorganic base, preferably an alkali metal or alkaline earth metal hydroxide, particularly preferably sodium hydroxide, before the addition of the etherification reagent so that alkali metal cellulose can form. The order of addition can also be reversed. In this case, the formation of alkali cellulose takes place in situ.

The base can be added in solid form or in the form of a solution. If exclusively solid bases are used, it may be necessary to add some water, since a certain amount of water must be present in the system during the alkalization.

For example, for a sufficient alkalization of cellulose, at least 1 mol of water should be present per mol of anhydroglucose, preferably at least 5 mol of water per mol of anhydroglucose, more preferably at least 10 mol of water per mol of anhydroglucose.

Overall, less than 55 mol, preferably less than 45 mol, more preferably less than 35 mol of water per mol of anhydro sugar should be used. More water leads to the formation of by-products and reduces the yield.

When the free amine is used, acid formed during etherification can be linked by the amino group. However, it is preferred to use at least 0.5 equivalent of base per mole of etherification reagent, more preferably at least 0.8 equivalent, to achieve sufficient reaction rate.

At most 1.5 equivalents of base should be used per mole of etherifying reagent, preferably at most 1.2 mol and in a particularly preferred embodiment 1-1.1 mol.

The amount of base must be increased accordingly if the etherifying reagent in the form of an ammonium salt e.g. is used as the hydrochloride. Then, in addition, at least an equimolar amount, based on the ammonium salt, of base must be added to remove the amine, e.g. from the hydrochloride, release.

The reaction is carried out in the presence of a water-miscible aprotic solvent in a stirred vessel or reaction mixer. The reaction can be carried out in a stirred vessel if the ratio of polysaccharide to slurry (slurry = aprotic water-miscible solvent + water) is 1:50 to about 1:10, preferably about 1:25 to 1:13 parts by weight , At higher ratios of up to about 1: 4 parts by weight of the approach may be harder to stir. In this case, a reaction mixer can be used become. These are, for example, under the name AU In One Reactor ^® by the company. Draiswerke, Mannheim or under the name Druvatherm ^® reactor. By the company Gebr. Lödige Ma¬ mechanical engineering, Paderborn, offered. These mixers generally consist of a horizontally arranged, mostly cylindrical mixing chamber. This is a wave, which is provided with eg paddle or pflugscharförmigen mixing elements. If the shaft rotates, the particles are ejected from the bed of mixed material and are confused and mixed in the space above the mix. The mixer may optionally be provided with further internals, such as so-called cutter heads or nozzles. [Karl Sommer in: "Mixing of Solids, 3. Designs of Solid - Solid Mixers, 3.3 Paddle Mixers", Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH Verlag GmbH & Co. KgaA, 2002. DOI: 10.1002 / 14356007.b02_27, Article Online Posting Date: June 15, 2000]

It is not known why the reaction with aminoalkyl derivatives in a mixture of a water-miscible aprotic solvent and a certain amount of water proceeds in significantly better yields than in other solvents.

The reaction is preferably carried out at temperatures from 40 ⁰ C to about 9O ⁰ C, particularly preferably 60 ° C to about 75 ⁰ C. The reaction time depends on the reactor, the type of polysaccharide or derivative and the amount of aminoalkyl derivative used, and is preferably from 30 minutes to about 4 hours.

After the reaction, the product is e.g. freed by filtration of salts and by-products. This is optionally neutralized before or after the filtration. Preference is given to neutralizing before filtration. The filter cake is washed with a suitable washing medium. As preferred washing media, in addition to the water-miscible aprotic solvents, e.g. acetone and their mixtures with water proven. In many cases, it is also possible to purify first with water and then with an organic solvent. However, depending on the nature of the product and the by-products, a suitable washing medium must be selected by appropriate experimentation. But it is also possible not to remove the by-products and use the product in uncleaned form for technical applications.

The product isolated from the reaction medium and optionally purified is dried and mashed. Commercially available devices can be used for this purpose.

With the process according to the invention amino-containing polysaccharides and derivatives can be prepared in simple, widespread systems and in high yield.

Another object of the invention are therefore amino group-containing polysaccharide derivatives a) substituents of the type - (CH ₂ ) _H -NR ₁ R ₂ bound to the cellulose or a side chain, eg hydroxyalkyl chain, wherein n is at least 2 and the radicals R ₁ and R _{2 are} independently aliphatic or branched or cyclic, optionally substituted by hetero atoms substituted alkyl or aryl substituents or H or two radicals R ₁ and R ₂ may form a ring together with the nitrogen, wherein R ₁ and R ₂ independently contain 1 to 24 carbon atoms and

b) contain alkyl substituents of the type R ₃ , wherein preferably R ₃ = - (CHa) _1n -CH ₃ with m = 0-3 and a DS ^ i> 0.1 and

c) contain hydroxyalkyl substituents of the type R ₄ , wherein preferably R ₄ = -CH ₂ - CH (C _p H _{2P + I} ) O- (CH ₂ -CH (CpH _{2P +} I) OJ ₉ -CrH ₂₁₊ I with p = 0 or 1, q = 0-30, r = 0 or 1 and an MSHydroxyaikyi> 0.1 and the

d) a total degree of substitution (sum of the individual degrees of substitution) of the substituents - (CHz) _n -NRiR ₂ , and R ₃ and R ₄ , determined from the nitrogen content [for substituents - (CH ₂ ) _I i-NR ₁ R ₂ ] or after Zeisel cleavage [for substituents R ₃ and R ₄ ], between 0.8 and 2.5 per anhydroglucose unit.

The invention will be explained in more detail by the following examples:

Examples

The indicated DS refers to pure aminoethylcellulose, ie the total amount was corrected for the water content, the chloride and acetate ion content as well as the sodium ion content. The sodium ion content was determined from the sulfate ash, assuming that it consists of 100% Na ₂ SO ₄ .

The chemicals were obtained from the trade. The nitrogen content was determined by the Kjeldahl method and is based on a double determination of the sample. The viscosities were determined in a solution of 2% by weight of the polymer at a shear rate of 2.55 s ^-1 with a rheometer of the type Rotovisko VT 550, from Haake.

Examples 1-2

Variation of the dispersant

Cellulose (17.2 g, dry content 94.24%) is dissolved in a mixture of the indicated dispersing agent (330.8 g) and water (41.1 g) in a 500 ml glass four-necked flat-bottomed round bottomed stirring apparatus with an impeller. Stirrer suspended.

Sodium hydroxide solution (32.2 g, 49.6% by weight in water) is added and, after 1 h at room temperature, diisopropylaminoethyl chloride hydrochloride (40 g) is added and the reaction mixture is heated to 70 ^° C. under a nitrogen atmosphere. After a reaction time of 4 h, the mixture is allowed to cool and neutralized with glacial acetic acid (12 g). The product is washed several times with 80% aqueous acetone and finally pure acetone, dried and ground.

* nB: not determined Protic or water-immiscible solvents were used in the comparative examples. The yields of the reaction are well below 50%.

Example 3

Cellulose (63.7 g, dry content approx. 95%) is suspended in a mixture of the specified dispersant and water in a 2 liter double-walled glass reactor with MIG stirrer.

Sodium hydroxide prills (59.2 g) is added and after 1 h at room temperature the propylaminoethylchlorid diisopropyl hydrochloride added (148.1 g) and the reaction mixture heated under a nitrogen atmosphere at 70 ⁰ C. After a reaction time of 4 h, the mixture is allowed to cool and enters the reaction mixture in acetone acetoacetate. The product is washed several times with ethanol / acetone / water 40/40/10 (wt .-%) and acetone, dried and ground.

PA = Isopropylalkohol TBA = tert-Butylakohol

PA = isopropyl alcohol TBA = tert-butyl alcohol

A significant reaction took place only in dioxane. The yield is> 50%.

Examples 4-6

The indicated amount of ground cellulose is suspended in a mixture of dimethoxyethane and water in a 500 ml glass four-necked round bottomed round bottomed stirring apparatus with an impeller stirrer.

Sodium hydroxide solution (about 50% by weight) is added and, after 1 h at room temperature, diethylaminoethyl chloride hydrochloride is added and the reaction mixture is filtered under nitrogen atmosphere. warmed to 7O ⁰ C. After a reaction time of 4 h, the mixture is allowed to cool and enters the reaction mixture in acetone acetoacetate. The product is washed several times with 80% aqueous acetone and finally pure acetone, dried and ground.

Examples 7-9

The procedure is as in the preceding examples, with the difference that diisopropylaminoethyl chloride is used.

In Example 9, the ratio of cellulose to slurry 1: 10.3 and is thus outside the preferred range. In this experiment it was observed that the approach was difficult to stir and therefore the reagents could not be sufficiently distributed.

Examples 10-13

In a 500 mL three-necked flask stirred with reflux condenser, ground cellulose (17.0 g, dry content 95.12%) is suspended in a mixture of dioxane (331 g) and water (57.5 g).

Sodium hydroxide prills (12 g) are added and, after 1 h at room temperature, 30 g of diisopropylaminoethyl hydrochloride are added and the reaction mixture is heated to the stated temperature under a nitrogen atmosphere. After a reaction time of 4 h, the batch is allowed to cool and enters the reaction mixture in acetone. The product is neutralized with acetic acid and gewa¬ several times with 80% aqueous acetone and finally acetone, dried and ground.

Examples 14-18

In a 500 mL three-necked flask stirrer, ground cellulose (17.3 g, dry content 93.6%) is suspended in a mixture of dimethoxyethane (331 g) and water (41 g).

Sodium hydroxide solution (50% by weight in water, 32.3 g) is added and, after 1 h at room temperature, 40 g of diisopropylaminoethyl hydrochloride are added and the reaction mixture is heated to the indicated temperature under a nitrogen atmosphere. After a reaction time of 4 h, the batch is allowed to cool and enters the reaction mixture in acetone. The product is neutralized with acetic acid and washed several times with 80% aqueous acetone and finally acetone, dried and ground.

-

-

In Example 18, the reaction temperature was out of the preferred range, resulting in a low yield.

Examples 19-24

In Examples 19-24, the procedure is as in Examples 14-18, with the difference that the reaction temperature is 7O ⁰ C and the composition of the liquid phase is varied. In Examples 23 and 24, diethylaminoethyl chloride hydrochloride (DEC) is used in an amount of 1.5 moles per mole of anhydroglucose. The amount of NaOH is also adjusted to 3 moles per mole of anhydroglucose (two moles per mole of etherifying reagent).

¹ DIC = di-isopropylaminoethyl chloride ² DEC = diethylaminoethyl chloride

From these examples, it is demonstrated that at water contents outside the preferred range, the yield drops below 50% (Examples 21 and 22).

Claims

claims 1. A process for the preparation of aminoalkylgruppenhaltiger polysaccharides and polysaccharidderivate, characterized in that a) dispersing a polysaccharide or polysaccharide derivative in a mixture of a water-miscible aprotic solvent and water, and b) the polysaccharide or polysaccharide derivative is alkalized with an inorganic base and c) during the alkalization sets the amount of water used in the range between 1 and 55 moles of water per Anhydroglycoseeinheit the polysaccharide or polysaccharidederivates and d) subsequently carrying out an amination with an etherifying reagent at optionally elevated temperature and then e) optionally neutralized and f) the reaction product is filtered off, washed and then optionally dried and ground. 2. The method according to claim 1, characterized in that a water-miscible ether is used as the water-miscible aprotic solvent. 3. The method according to any one of the preceding claims, characterized in that the ratio of polysaccharide or polysaccharide derivative to the total amount of water-miscible aprotic solvent and water is 1: 4 to 1: 50 parts by weight. 4. The method according to any one of the preceding claims, characterized in that the reaction is carried out at temperatures of about 40 to 90 ⁰ C. 5. The method according to any one of the preceding claims, characterized in that is used as the polysaccharide cellulose. 6. The method according to any one of the preceding claims, characterized in that as polysaccharide one or more polysaccharides from the group pullulan, starch, dextran, guar, xylans, xanthan gum or carrageenan be used. 7. The method according to any one of the preceding claims, characterized in that are used as polysaccharide derivatives cellulose ethers. 8. The method according to any one of the preceding claims, characterized in that in the reaction, a polysaccharide is used and about 2 moles of Veretherungsreagenz per hydrosugar or less are used. 9. The method according to any one of the preceding claims, characterized in that 0.01 to 1, 5 mol Veretherungsreagenz per anhydroglucose unit (AGU) are used. 10. The method according to any one of the preceding claims, characterized in that 0.1 to 3 moles of etherifying reagent per AGU are used. 11. The method according to any one of the preceding claims, characterized in that in the purified reaction product, more than 50% of the etherifying reagent used is bound to the cellulose, calculated from the nitrogen content of the purified reaction product. 12. amino-containing polysaccharide derivatives the a) substituents of the type - (CH ₂ ) _n -NR ₁ R ₂ contain, wherein n is at least 2 and the Radicals Ri and R ₂ independently of one another are aliphatic or branched or cyclic, optionally heteroatom-substituted alkyl or aryl substituents or H, or two radicals R ₁ and R ₂ together with the nitrogen can form a ring, where R ₁ and R ₂ independently of one another contain 1 to 24 C atoms and b) contain alkyl substituents of the type R ₃ , with preference

- (CH ₂ ) _m -CH ₃ with m = 0-3 and a DS> 0.1 and c) a total degree of substitution (sum of the individual degrees of substitution) of the substituents - (CH ₂ ) _H -NR ₁ R ₂ and R ₃ , determined from the nitrogen content [for substituents - (CH ₂ ) _D -NRiR ₂ ] or according to Zeisel Cleavage [for substituents R ₃ ], between 0.8 and 2 per anhydroglucose unit. 13. Amino group-containing polysaccharide derivatives, which a) substituents of the type - (CH ₂ ) _n -NRiR ₂ bound to the cellulose or a side chain, eg hydroxyalkyl chain, in which n is at least 2 and the radicals R 1 and R ₂ independently of one another are aliphatic or branched or cyclic, - optionally substituted by hetero atoms alkyl or aryl substituents or H or two radicals R ₁ and R ₂ together with the nitrogen can form a ring, wherein R ₁ and R ₂ independently of one another contain 1 - 24 carbon atoms and and b) contain alkyl substituents of the type R ₃ , wherein preferably R ₃ = - (CH ₂ ) _m -CH ₃ with m = 0-3 and a DS _A i _k yi> 0.1 and c) hydroxyalkyl substituents of type R ₄ , wherein preferably R ₄ = -CH ₂ - CH (C _p H ₂ p ₊ i) O- {CH ₂ -CH (CpH _{2p +} i) O} _q -C _r H _{2r +} i with p = 0 or 1, q = 0-30, r = 0 or 1 and an MSHydroxyaikyi> 0, 1 and the d) a total degree of substitution (total of the individual degrees of substitution) of the substituents - _{(CH2) I1} -NR _I R _2, and R ₃ and R _4, as determined from the nitrogen content [the substituent - (CH ₂₎ Q-NRiR _2] or after Zeisel cleavage [for substituents R ₃ and R ₄ ], between 0.8 and 2.5 per anhydroglucose unit.