GB2270314A - Preparation of cellulose ethers - Google Patents

Abstract

In a process for the preparation of cellulose ion exchangers an initially moist beaded cellulose is first impregnated with an etherifying agent, partially or completely dried and then etherified by adding an aqueous alkali metal hydroxide and raising the temperature. The products prepared according to the invention can be used as separating materials for analytical and preparative purposes in chemistry, biochemistry, medicine and pharmacy.

Description

"A PROCESS FOR THE PREPARATION OF CEIl1ULOSIC ION EXCHANGE RESINS" The invention relates to a process for the preparation of cellulosic ion exchange resins. Such resins are useful in many branches of chemistry, biochemistery, medicine and pharmacy, particularly for analytical and preparative purposes.

There are many known processes for the preparation of cellulosic ion exchange resins. See, for example, Rybak, M., Brada, Z and Hais, I.N.: Säulenchromatographie an Celluloseionenaustauschern (Column Chromatography on Cellulose Ion Exchangers), Gustav Fischer Verlag, Jena, 1966; Peterson, E.A.: Cellulosic Ion Exchangers, North-Holland Publ. Co., Amsterdam, 1970. Most of these known processes involve reacting pulverulent or fibrous cellulose with a suitable etherifying agent(s) in the presence of a concentrated alkali metal hydroxide solution. The products so produced exhibit unfavrouable flow properties, when used in chromatography columns, and possess inadequate protein binding capacities, all due to their low porosity.

The development of beaded cellulose ion exchangers or resins allowed for substantial improvements in these properties. The starting material used for the preparation of such exchangers or resins is beaded cellulose, regenerated predominantly from viscose, which is characterised by having a macroporous structure. Beaded cellulose can be converted into an ion exchange resin by one of the aforementioned known processes, however, the final product's properties and/or reagent yield are dependant, to a significant extent, on whether the beaded cellulose is used in a moist state tCS-US 195 205) or dry (CS-US 199 420). If moist cellulose beads are used, the product will have a low exchange capacity, unless a very large excess of modifying reagent is used.Starting with dry cellulose beads will result in a product having a decreased porosity, which is a disadvantage, especially when it is used in the separation of high molecular weight biological macromolecules.

It has been found that the inherent porosity of the beaded cellulose can be better maintained and the amount of modifying reagent required reduced if water is completely or at least partially displaced, from the initially moist beaded cellulose, by a suitable organic solvent and if the modification reaction is subsequently carried out in the presence of an organic solvent tDE-OS 2 005 408, CS-US 212 131). These processes, however, not only involve expensive drying or partial solvent exchange procedures, the latter requiring large amounts of flammable organic solvents, but also, the beaded cellulose can be structurally and chemically changed by the concentrated sodium hydroxide solution added thereto, prior to the etherification reaction.

An object of the present invention is to provide a simple cost-effective process for the preparation of a beaded cellulose ion exchanger or resin which gives a product with improved properties, while avoiding the aforementioned disadvantages of known processes.

A further object of the invention is to produce a beaded cellulose ion exchanger with advantageous properties; that is with a high porosity and a highly accessible matrix and/or a high exchange capacity.

According to the present invention there is provided a process for the preparation of a cellulosic material for use as an ion exchanger, comprising impregnating moist porous cellulose with an etherifying agent, at least partially removing the water from the resulting mixture and etherifying the cellulose in the presence of an added alkali.

Thus the invention can, in an embodiment, involve a procedure in which beaded particles of regenerated cellulose, in an intiailly moist or partially predried state, are first impregnated with an etherifying agent, the water still present in the beads and/or introduced with the etherifying agent is then partially completely removed and, finally, etherification is effected by the addition of an aqueous alkali metal hydroxide. The etherification reaction can be carried out in a manner known per se at a temperature of 50 to 950C; the reaction time being preferably between 10 and 360 min. The resulting cellulose ion exchanger can be worked up and/or purified in a conventional manner, by neutralization of any excess alkali metal hydroxide with dilute hydrochloric or sulphuric acid and thorough extraction of the by-products by washing.

The macroporous structure of the beaded cellulose is maintained, throughout the entire modification process, by the introduction of the initially inert etherifying agent into the voids in the cellulose. This is preferably effected simply by mixing the moist beads, whose water content is normally 80 to 95% by weight, with the solid etherifying agent, or a concentrated solution thereof, for about 10 to 120 min. Under certain circumstances, it can prove favourable to remove part of the water from the moist beads before the etherifying agent is added. However, so as to avoid reducing the porosity too much and to maintain the cellulose accessible to the etherifying agent, the water content, preferably, should not be allowed to fall below 50%. Once the cellulose has been impregnated with the etherifying agent, it can be dried without its pore system collapsing irreversibly.The water is preferably removed down to a proportion of 0 to 40% by weight, based on the impregnated product; this follows from the preferred range for the cellulose:water molar ratio in the reaction mixture of 1:5 to 1:35. Said cellulose:water molar ratio and a cellulose:alkali metal hydroxide molar ratio of 1:0.2 to 1:4 can be established by the additon of concentrated aqueous alkali metal hydroxide solution, especially 10 to 45% NaOH; the preferred alkali metal hydroxide being sodium hydroxide. The sodium hydroxide solution is preferably applied to the impregnated beaded cellulose by spraying, while the reaction medium is simultaneously mixed.

The molar ratio of cellulose to etherifying agent which is preferred to achieve the desired exchange capacity is 1:0.2 to 1:2.

Where molar ratios of cellulose or a cellulose derivative are discussed in this specification, these are provided on the basis of the molecular weight of the glucose (or derivative) unit, from which the cellulose molecular is built, and not upon the molecular weight of an entire such molecule.

The following compounds known for the preparation of cellulose ion exchangers can be used as the etherifying agent: halogenoalkylcarboxylic acids, e.g. monochloroacetic acid or chloropropionic acid, halogenoalklyphosphonic acids, e.g. chloromethyl phosphonic acid or ss-chloroethylphosphonic acid, halogenoalkylsulphonic acids, e.g. chloromethylsulphonic acid or ss-chloroethylsulphonic acid, or salts thereof. Basic cellulose ion exchangers are preferably prepared using halogenoalkylamines, e.g.

ss-chloroethyldiethylamine, ss-chloroethylpiperidine or ss-chloroethyldiethyl(2-hydroxypropyl)ammonium chloride.

The exchange capacity, based on the volume of the exchanger, of a product of the inventive process can be increased by starting the process from a crossliked beaded cellulose and/or by adding a crosslinking agent to the cellulose before or during etherification. This modification causes the cellulose beads to undergo limited swelling. Epichlorohydrin in a molar ratio to the cellulose of 0.01 to 1 is preferred as the crosslinking agent, but it is also possible to use other suitable bifunctional or polyfunctional substances.

The advantages of the inventive process are throught to be derived, firstly, from the fact that the initial impregnation of the starting beaded cellulose, with the etherifying agent, makes it possible substantially to prevent the pore system of the cellulose from collapsing during the subsequent drying process. Secondly, reagent utilisation is improved by the fact that etherification is carried out in the presence of only relatively small amounts of water.

The intensive mixing of the reaction medium is not impaired by working with small amounts of water, because it is free-flowing and/or friable or pulpy, and even distribution of the alkali metal hydroxide solution can be ensured by spraying it onto the reaction mixture.

If, for equipment-related or other reasons, it should nevertheless be necessary to carry out the reaction with a long liquor ratio, an inert organic solvent, e.g. acetone, ethanol, isopropanol, toluene or chlorobenzene may be added to the reaction mixture.

The proportion of solvent to be added here is determined primarily by the expense involved in recovering the solvent as quantitatively as possible, and by the type of reaction vessel. From the point of view of solvent recovery, it is advantageous to distil the solvent completely out of the reaciton medium during or after the reaction and only then to undertake the washing processes.

Practical Examples Example 1 205 g of suction-filtered moist beaded cellulose with a cellulose content of 40.5 g (0.25 mol) were mixed with a solution of 10 g (0.058 mol) of -chloro- ethyldiethylamine hydrochloride in 100 ml of water for 30 min in a rotary evaporator at room temperature and the mixture was then dried to constant weight at 600C under vacuum. After the impregnated beaded cellulose had cooled to room temperature, 12 g (0.30 mol) of NaOH dissolved in 100 ml (5.56 mol) of water were added dropwise, with continuous thorough mixing, and the mixture was then heated for 30 min at 900C. The product was cooled to room temperature, acidified with 0.5 N aqueous hydrochloric acid and washed with water.

The beaded diethylaminoethyl cellulose (beaded DEAE-cellulose) obtained had an ion exchange capacity of 0.5 meq/g, a sedimentation volume of 8.0 ml/g and a protein binding capacity of 114 mg of methaemoglobin/ ml.

Example 2 A beaded DEAE-cellulose was prepared analogously to Example 1, except that 20 g (0.116 mol) of p- chloroethyldiethylamine hydrochloride (0.464 mol/mol of cellulose) were used. The product obtained had an ion exchange capacity of 1.1 meq/g, a sedimentation volume of 8.7 ml/g and a protein binding capacity of 124 mg of methaemoglobin/ml.

Example 3 205 g of suction-filtered moist beaded cellulose were first treated with a mixture of 5 parts of 30% formaldehyde and 1 part of 36% hydrochloric acid for 2 h at room temperature. After washing and suction filtration, the beaded cellulose crosslinked in this way was reacted as in Example 1. The amounts of cellulose, p-chloroethyldiethylamine hydrochloride, NaOH and water used were 0.25, 0.149, 0.5 and 5.56 mol respectively.

The beaded DEAE-cellulose obtained had an ion exchange capacity of 1.22 meq/g and a sedimentation volume of 10.4 ml/g.

Example 4 A beaded DEAE-cellulose was prepared analogously to Example 1, the molar amounts of cellulose, p- choroethyldiethylamine hydrochloride, NaOH and water used being 0.25, 0.232, 0.5 and 5.56 mol, and 0.05 mol of epichlorohydrin also being added together with the sodium hydroxide solution.

The product obtained had an ion exchange capacity of 1.95 meq/g, a sedimentation volume of 4.9 ml/g and an insulin binding capacity of 450 mg/g.

Example 5 205 g of suction-filtered moist beaded cellulose were impregnated with 40 g (0.232 mol) of p- chloroethyldiethylamine hydrochloride and dried as in Example 1. A solution of 20 g (0.5 mol) of NaOH and 2.3 g (0.025 mol) of epichlorohydrin in 25 ml (1.388 mol) of water was then sprayed on at room temperature over 10 min, with continuous mixing of the impregnated beaded cellulose, and the mixture was heated for 30 min at 90"C. After acidification and washing, a beaded DEAE-cellulose with an ion exchange capacity of 2.05 meq/g and a sedimentation volume of 9.7 ml/g was obtained.

Example 6 A beaded DEAE-cellulose was prepared analogously to Example 5, the reaction medium being suspended in 500 ml of isopropanol after spraying of the sodium hydroxide solution/epichlorohydrin mixture, and then being heated for 30 min at 90"C. After cooling, the product was filtered off with suction and washed with water, 0.5 N aqueous HCl and water again. A beaded DEAE-cellulose with an ion exchange capacity of 1.5 meq/g, a protein binding capacity (methaemoglobin) of 160 mg/ml and a sedimentation volume of 5.43 ml/g was obtained.

Example 7 A beaded DEAE-cellulose was prepared analogously to Example 6, the reaction medium being suspended in 500 ml of acetone after spraying of the sodium hydroxide solution/epichlorohydrin mixture, and being reacted for 6 h at the boiling point. The acetone was then distilled off. The product obtained after acidification and washing had an ion exchange capacity of 1.44 meq/g and a sedimentation volume of 8.5 ml/g.

Example 8 A beaded DEAE-cellulose was prepared analogously to Example 1, the 205 g of suction-filtered moist beaded cellulose first being predried down to 81 g, corresponding to a water content of 50%, and then being impregnated with p-chloroethyldiethylamine hydrochloride and reacted as described. The product obtained had an ion exchange capacity of 0.45 meq/g and a sedimentation volume of 4.3 ml/g.

Example 9 A beaded DEAE-cellulose was prepared analogously to Example 1, the beaded cellulose impregnated with the p-chloroethyldiethylamine hydrochloride solution being dried until it contained only 20 g of water (28% by weight). 10 g of NaOH dissolved in 80 g of water were then added. The reaction medium was reacted and worked up as described. The product obtained had an ion exchange capacity of 0.55 meq/g and a sedimentation volume of 7.2 ml/g.

Example 10 205 g of suction-filtered moist beaded cellulose with a cellulose content of 40.5 g (0.25 mol) were mixed in a rotary evaporator with a solution of 20 g (0.125 mol) of piperidinoethyl chloride hydrochloride in 50 ml of water for 30 min at room temperature and the mixture was then dried at 60"C under vacuum. A solution of 20 g (0.5 mol) of NaOH in 50 ml (2.78 mol) of water was then added dropwise and the mixture was heated for 30 min at 90"C. After cooling, the reaction medium was washed with 0.5 N NaOH, water, 0.5 N HCl and water again. The product obtained had a protein binding capacity of 72 mg of methaemoglobin/ml.

Example 11 205 g of suction-filtered moist beaded cellulose (0.25 mol of cellulose) were mixed with a solution of 20.25 g (0.175 mol) of sodium monochloroacetate in 100 ml of water for 30 min in a rotary evaporator at room temperature and the mixture was then dried to constant weight at 60"C under vacuum. After cooling to room temperature, 8 g (0.2 mol) of NaOH dissolved in 73 g (4.05 mol) of water were added dropwise. The mixture was heated for 120 min at 70"C and, after cooling, washed with water until the washings gave a neutral reaction.

The beaded carboxymethyl cellulose obtained had an exchange capacity of 1.0 meq/g and a sedimentation volume of 8.6 ml/g.

Example 12 205 g of suction-filtered moist beaded cellulose (0.25 mol of cellulose) were predried to a weight of 100 g in a rotary evaporator at 600C and, after cooling, mixed with 36 g (0.25 mol) of p-chloroethylphosphonic acid for 30 min at room temperature. A solution of 32 g (0.8 mol) of NaOH in 40 ml of H2O was then sprayed on and the mixture was heated for a further 6 h at 90"C. After cooling, the product was washed with water, 0.1 N NaOH and water again.

The beaded cellulose obtained had a cation exchange capacity of 0.7 meq/g.

Example 13 205 g of suction-filtered moist beaded cellulose (0.25 mol of cellulose) were mixed with a solution of 10.4 g (0.0626 mol) of sodium p-chloroethylsulphonate in 50 ml of water and dried at 60"C. A solution of 4 g (0.1 mol) of NaOH in 25 ml (1.388 mol) of water was then sprayed on to the impregnated product and the reaction medium was heated for 3 h at 80"C. After cooling, the product was washed with 0.5 N H2SO4, water, 0.5 N NaOH and water again.

The beaded cellulose exchanger obtained had an ion exchange capacity of 0.4 meq/g.

Claims (16)

rTzIMs

1. A process for the preparation of a cellulosic material for use as an ion exchanger, comprising impregnating moist porous cellulose with an etherifying agent, at least partially removing the water from the resulting mixture and etherifying the cellulose in the presence of an added alkali.

2. A process as claimed in claim 1, wherein the cellulose is a beaded cellulose.

3. A process as claimed in either claim 1 or claim 2, wherein the cellulose is a regenerated cellulose, preferably regenerated from viscose.

4. A process as claimed in any of the preceding claims, wherein the cellulose is admixed with the etherifying agent in a molar ratio of cellulose to etherifying agent of 1:0.2 - 1:2, to thereby cause the latter to impregnate the former.

5. A process as claimed in any of the preceding claims, wherein the water is at least partially removed down to a concentration of 0-40% by weight based upon the impregnated cellulose.

6. A process as claimed in any of the preceding claims, wherein the alkali is an aqueous alkali metal hydroxide, preferably sodium hydroxide.

7. A process as claimed in claim 6, wherein the aqueous alkali metal hydroxide is added in an amount sufficient to provide a molar ratio of cellulose to alkali metal hydroxide of 1:0.2 - 1:4.

8. A process as claimed in any of the preceding claims, wherein sufficient water is removed from the impregnated cellulose to provide a molar ratio of cellulose to water of 1:5 - 1:35, prior to etherification.

9. A process as claimed in any of the preceding claims, wherein etherification is carried out at a temperature of 50 - 950C, maintained for a period of 10 - 360 minutes.

10. A process as claimed in any of the preceding claims, wherein a solution of the etherifying agent is admixed with the moist cellulose, thereby causing the etherifying agent to impregnate the cellulose.

11. A process for the preparation of a cellulosic ion exchanger, comprising reacting cellulose with an etherifying agent in the presence of alkali metal hydroxide and water, characterised in that moist, beaded particles of regenerated cellulose, with a water content of 50 to 95% by weight, are first mixed with the etherifying agent in solid or dissolved form, the molar ratio of cellulose to etherifying agent being 1:0.2 to 1:2, water is then removed from the resulting mixture down to a proportion of 0 to 40% by weight, based on the impregnated beaded cellulose, an aqueous alkali metal hydroxide is added in an amount such that the molar ratio of cellulose to alkali metal hydroxide in the reaciton mixture is 1:0.2 to 1:4 and the molar ratio of cellulose to water is 1:5 to 1: :35, and finally the mixture is reacted for 10 to 360 min at 50 to 950C.

12. A process as claimed in any of the preceding claims, wherein the etherifying agent is a halogenalkylcarboxylic acid, a halogenoalkylphosphonic acid, a halogenoalkylsulphonic acid or a salt thereof, or a halogenoalkylamine.

13. A process as claimed in any of the preceding claims, wherein the cellulose is crosslinked before or during etherification.

14. A process as claimed in any of the preceding claims, wherein the reaction medium additionally contains an inert organic solvent.

15. A process for the preparation of a cellulosic material for use as an ion exchanger substantially as hereinbefore described in any of examples 1-13.

16. A cellulosic material for use as an ion exchanger, whenever produced by a process as claimed in any of the preceding claims.