JP5362483B2 - Method for producing alkyl etherified carboxyalkyl cellulose - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an alkyl-etherified cellulose derivative having a high alkyl-etherifying substitution degree. <P>SOLUTION: In a method of reacting a cellulose or a derivative thereof (A) with an alkylating agent (B) using an alkali C, an objective compound is obtained in a high yield and also a compound having effective purity is obtainable through an industrial manufacturing method, by using a specific phase-transfer catalyst. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

The present invention relates to a method for producing an alkyl etherified cellulose derivative. Specifically, the present invention relates to a method for producing an alkyl etherified cellulose derivative having a high degree of alkyl ether substitution.

  Conventionally, as an alkyl etherification method of cellulose or a derivative thereof, a method of reacting an alkyl halide with, for example, carboxyalkyl cellulose in the presence of a strong alkali such as caustic soda is known (for example, Patent Document 1).

However, the reaction between the carboxyalkyl cellulose and the alkali first produces an alcoholate and water, and then the reaction between the produced alcoholate and the alkylating agent produces a highly hydrophobic alkyl etherified cellulose derivative and salt. As the reaction progresses, the heterogeneity of the reaction system increases and the aggregation of the alkyl etherified cellulose derivative progresses, so that it is difficult to obtain a product having a high degree of alkyl ether substitution.
Japanese Patent Laid-Open No. 55-118901

  An object of the present invention is to provide a method for producing an alkyl ether cellulose derivative having a high degree of alkyl ether substitution.

As a result of diligent research, the present inventor has found that the present invention can be solved by reacting in the presence of a phase transfer catalyst (D) having a specific chemical structure together with alkali (C), and has completed the present invention. .
That is, the present invention relates to an alkyl ether characterized in that cellulose or a derivative thereof (A) and an alkylating agent (B) are reacted with an alkali (C) in the presence of a phase transfer catalyst (D) having a specific chemical structure. It is a manufacturing method of a chlorinated cellulose derivative (E).

  According to the present invention, by selecting a phase transfer catalyst having a specific chemical structure, a decrease in reactivity due to aggregation that proceeds with the alkyl etherification reaction is suppressed. A cellulose derivative is obtained.

  The present invention relates to an alkyl ether characterized in that cellulose or a derivative thereof (A) and an alkylating agent (B) are reacted with an alkali (C) in the presence of a phase transfer catalyst (D) having a specific chemical structure. It is a manufacturing method of a chlorinated cellulose derivative (E).

In the present invention, cellulose or cellulose derivative (A) as a starting material includes plant cellulose obtained from cotton linter, wood pulp, dissolved pulp, etc .; bacterial cellulose produced by microorganisms belonging to the genus Acetobacter, etc .; carboxymethyl cellulose Carboxyalkyl celluloses such as carboxyethyl cellulose and carboxypropyl cellulose; hydroxyalkyl celluloses such as hydroxyethyl cellulose and hydroxypropyl cellulose; alkyl celluloses such as methyl cellulose, ethyl cellulose and isopropyl cellulose; hydroxypropyl methylcellulose and the like.
Preferred are carboxyalkyl cellulose, hydroxyalkyl cellulose and alkyl cellulose, and particularly preferred is carboxyalkyl cellulose.

In the present invention, as the alkylating agent (B) used for alkyl etherification of cellulose or its derivative (A), alkyl chlorides such as methyl chloride, ethyl chloride, propyl chloride, butyl chloride, isopropyl chloride; methyl bromide And alkyl bromides such as ethyl bromide, propyl bromide, butyl bromide and isopropyl bromide; and dialkyl sulfuric acids such as dimethyl sulfate, diethyl sulfate, dipropyl sulfate, dibutyl sulfate and diisopropyl sulfate.
Alkyl chloride is preferable, and ethyl chloride and methyl chloride are particularly preferable.

  The charge ratio of cellulose or its derivative (A) and alkali (C) is usually 1 / 0.8 to 1/10 as the equivalent ratio of hydroxyl group / alkali (C) of (A), and 1/1 to 1 / 8 is preferred.

Examples of the alkali (C) include solids of sodium hydroxide, potassium hydroxide and lithium hydroxide, preferably sodium hydroxide and potassium hydroxide, more preferably sodium hydroxide. These solid alkali metal hydroxides may be used alone or as a mixture of two or more.
These solid alkali metal hydroxides may be in the form of granules, flakes, or powders. The size is preferably 1 to 5 mm in diameter for granular materials, 0.5 to 3 cm square for flakes, and preferably 30 to 100 μm for powders, but the present invention is not limited thereto. Granularity is preferable for the handling of workers.
The weight ratio (A) / (C) of cellulose or its derivative (A) and alkali (C) is usually 1 / 0.1 to 1 / 2.0, and 1 / 0.3 to 1 / 1.5. Is preferred.

In the production method for obtaining a high degree of alkyl etherification substitution according to the present invention, it is essential to carry out the reaction in the presence of the phase transfer catalyst (D), and the phase transfer catalyst (D) is represented by the following general formula (1). ).

[In the formula (1), R ¹ and R ² are each independently a linear or branched aliphatic hydrocarbon group having 1 to 8 carbon atoms; R ³ is a linear or branched fatty acid having 1 to 22 carbon atoms; Represents a group hydrocarbon group. R ⁴ represents a linear or branched aliphatic hydrocarbon group having 8 to 22 carbon atoms or an arylalkyl or arylalkenyl group having 7 to 22 carbon atoms; X ⁻ represents a monoanion of the acid (F). ]

R ¹ and R ² carbon atoms each independently may represent a straight-chain aliphatic hydrocarbon groups of 1-4, and specific examples thereof include a methyl group, an ethyl group, a propyl group, etc. butyl group.

R ³ represents a linear or branched aliphatic hydrocarbon group having 1 to 22 carbon atoms, and specific examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, a hexyl group, an octyl group, Nonyl group, decyl group, dodecyl group, tetradecyl group, hexadecyl group, octadecyl group, oleyl group, alkyl group obtained by removing hydroxyl group from alcohol derived from coconut oil (hereinafter abbreviated as coconut oil alkyl group), oleyl group, etc. Examples of the branched hydrocarbon group include isopropyl group and 2-ethylhexyl group. Among these, a linear aliphatic hydrocarbon group having 1 to 20 carbon atoms is preferable, and a linear aliphatic hydrocarbon group having 1 to 18 carbon atoms is more preferable.

R ⁴ represents a linear or branched aliphatic hydrocarbon group having 8 to 22 carbon atoms, or an arylalkyl or arylalkenyl group having 7 to 22 carbon atoms.
Examples of the linear aliphatic hydrocarbon group include octyl group, nonyl group, decyl group, dodecyl group, tetradecyl group, hexadecyl group, octadecyl group, coconut oil alkyl group and oleyl group, and branched aliphatic hydrocarbon groups. Examples of the group include a 2-ethylhexyl group. Among these, a linear aliphatic hydrocarbon group having 8 to 20 carbon atoms is preferable, and a linear aliphatic hydrocarbon group having 10 to 18 carbon atoms is more preferable.

  Examples of the arylalkyl group having 7 to 22 carbon atoms include a benzyl group and a phenethyl group, and examples of the arylalkenyl group include a styryl group and a cinnamyl group. Among these, an arylalkyl group having 7 to 15 carbon atoms is preferable, and an arylalkyl group having 7 to 10 carbon atoms is more preferable.

Examples of the quaternary ammonium cation constituting the phase transfer catalyst (D) represented by the formula (1) include a case where R ⁴ is an aliphatic hydrocarbon group and an arylalkyl group.
Specific examples of the aliphatic hydrocarbon group represented by R ⁴ include those having one long-chain alkyl group (trimethyldodecyl ammonium, trimethyl tetradecyl ammonium, trimethyl hexadecyl ammonium, trimethyl octadecyl ammonium, trimethyl palm oil alkyl ammonium, trimethyl-2 -Ethylhexylammonium, dimethylethyldodecylammonium, dimethylethyltetradecylammonium, dimethylethylhexadecylammonium, dimethylethyloctadecylammonium, dimethylethylcoconut alkylammonium, dimethylethyl-2-ethylhexylammonium, methyldiethyldodecylammonium, methyldiethyltetradecyl Ammonium, methyl diethyl hexadecyl ammonium, methyl diethyl Octadecylammonium, methyldiethyl coconut oil alkylammonium and methyldiethyl-2-ethylhexylammonium, etc.) having two long chain alkyl groups (6-22 carbon atoms) (dimethyldihexylammonium, dimethyldioctylammonium, dimethyldidecylammonium and And those having one long-chain alkenyl group (8 to 22 carbon atoms) (such as trimethyloleylammonium, dimethylethyloleylammonium and methyldiethyloleylammonium).
Preferably, dimethyl didecyl ammonium, trimethyl hexadecyl ammonium, methyl diethyl dodecyl ammonium, and methyl diethyl coconut oil alkyl ammonium are used.

Specific examples of R ⁴ being an arylalkyl group include, for example, dimethyldecylbenzylammonium, dimethyldodecylbenzylammonium, dimethyltetradecylbenzylammonium, dimethylhexadecylbenzylammonium, dimethyl coconut oil alkylbenzylammonium, dimethyloleylbenzylammonium and dimethyl- Examples include 2-ethylhexyl benzyl ammonium.
Preferred examples include dimethyldodecylbenzylammonium, dimethyl coconut oil alkylbenzylammonium, dimethyloleylbenzylammonium and dimethyl-2-ethylhexylbenzylammonium.

  Among these, dimethyldidecylammonium, dimethyldodecylbenzylammonium, trimethylhexadecylammonium, dimethyl coconut oil alkylbenzylammonium, dimethyloleylbenzylammonium and dimethyl-2-ethylhexylbenzylammonium are preferable from the viewpoint of heat resistance.

X < ^- > in General formula (1) represents the monoanion of an acid (F).
Examples of the acid (F) include inorganic acids and organic acids, and inorganic acids are preferable.
Specific examples of inorganic acids include hydrochloric acid, nitric acid, sulfuric acid, sulfurous acid, bisulfite, phosphoric acid, phosphorous acid, hypophosphoric acid, metaphosphoric acid, hypophosphorous acid, amidophosphoric acid, carbonic acid, bicarbonate, hydrobromic acid, hydrogen iodide. Examples include acids, orthoboric acid, metaboric acid, sulfamic acid and the like.
Of these, preferred are hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, phosphoric acid, and phosphorous acid.

Among (D), from the viewpoint of reactivity, dimethyldidecylammonium chloride and bromide, dimethyldodecylbenzylammonium chloride and bromide, trimethylhexadecylammonium chloride and bromide, dimethyl coconut oil alkylbenzylammonium chloride, and dimethyl-2 -Chloride.

The amount of the phase transfer catalyst (D) added is usually 0.1 to 20% by weight, preferably 0.1 to 10% by weight, based on cellulose or its derivative (A).

In the present invention, it is preferable to use a solvent for the purpose of dissolving, swelling, or dispersing cellulose or its derivative (A) during the alkyl etherification reaction.
Examples of the solvent include aromatic hydrocarbon solvents such as toluene, xylene, ethylbenzene, and tetralin; aliphatic or alicyclic hydrocarbon solvents such as n-hexane, n-heptane, mineral spirit, and cyclohexane; methyl chloride, Halogen solvents such as methyl bromide, methyl iodide, methylene dichloride, carbon tetrachloride, trichloroethylene, perchloroethylene; esters such as ethyl acetate, butyl acetate, methoxybutyl acetate, methyl cellosolve acetate, ethyl cellosolve acetate, or ester ethers Solvents: Ether solvents such as ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethyl ether, tetrahydrofuran, dioxane, etc .; acetone, methyl ethyl ketone, methyl isobutyl Ketone solvents such as ruketone, di-n-butyl ketone and cyclohexanone; alcohol solvents such as t-butanol; amide solvents such as dimethylformamide and dimethylacetamide; sulfoxide solvents such as dimethyl sulfoxide, and complex such as N-methylpyrrolidone Examples thereof include cyclic compound solvents and mixed solvents of two or more of these.
The weight ratio [solvent / (A)] of the solvent at the start of the alkyl etherification reaction and cellulose or its derivative (A) is usually 0/1 to 10/1, preferably 0.1 / 1 to 4/1. is there.

Further, water can be used for the purpose of accelerating the reaction by swelling cellulose or its derivative (A).
The weight ratio [water / (A)] of water and (A) at the start of the alkyl etherification reaction is usually 0/1 to 0.3 / 1, preferably 0.01 / 1 to 0.15 / 1. . If the amount of water exceeds this range, the heterogeneity increases and the slurry-like reaction system cannot be maintained, not only causing aggregation, but also reducing the efficiency of the alkylating agent in the main reaction.

  The alkyl etherified cellulose derivative (E), which is the target compound of the present invention, reacts cellulose or its derivative (A) with an alkylating agent (B) in the presence of an alkali (C) and a phase transfer catalyst (D). By making it, the alkyl etherification substitution degree of (E) can be made high with 70 to 100%. Preferably they are 80%-100%, More preferably, they are 85%-100%.

Here, the “alkyl etherification substitution degree” in the present invention represents the average value of the ratio of the number of functional groups alkylated in the hydroxyl group per glucose ring unit of cellulose or its derivative (A) as a percentage. Define as a value.
For example, when (A) is a carboxymethyl cellulose in which 0.5 carboxymethyl group is substituted with a carboxymethyl group as a raw material and 2.1 of the remaining 2.5 is further alkyl etherified The degree of etherification substitution is 84%.
Specifically, it is obtained by cleaving the alkyl ether bond of (E) with hydroiodic acid, liberating iodine from the resulting iodic acid, and measuring this with sodium thiosulfate. Details will be described later.

The reaction temperature of the alkyl etherification reaction is usually 40 ° C to 180 ° C, preferably 60 to 160 ° C, more preferably 80 to 140 ° C. If it is less than 40 ° C., the reaction proceeds very slowly and is not efficient. If the temperature exceeds 160 ° C., corrosion may occur even if the material of the container is SUS316L having good durability.

  The reaction is preferably performed in an inert gas atmosphere such as nitrogen (oxygen concentration is preferably 100 ppm or less).

The order of adding cellulose or its derivative (A), alkylating agent (B), alkali (C) and phase transfer catalyst (D) is not particularly limited as long as no rapid reaction occurs, but (A), (D ), And if necessary, water and a solvent are mixed, and then (C) is dispersed with stirring. After repeatedly reducing the pressure at room temperature with an inert gas such as nitrogen, the pressure is reduced and (B) is added dropwise. The method is preferred.
The method of mixing (A), (B), and (C) and adding (C) at the end is not preferable because the product is likely to be colored by the heat of dissolution of (C) or a rapid reaction.

  In the present invention, after alkyl etherification, water and an acid such as sulfuric acid, hydrochloric acid and phosphoric acid are added to the reaction product, and the precipitate is washed with filtered water and dried to separate the alkyl etherified cellulose derivative (E), Can be purified.

The use of the alkyl etherified cellulose derivative obtained by the present invention is not particularly limited. However, it is used for applications in which the solubility of the product in water due to pH change or film forming ability is used.
Usually, it can be used as an additive for drugs such as pharmaceuticals, particularly enteric coating agents, bitterness masking agents, or hair hair setting agents.

  Hereinafter, although an example and a comparative example explain the present invention, the present invention is not limited to this. Hereinafter, unless otherwise specified, “parts” means “parts by weight” and% means% by weight.

  The method for measuring the degree of alkyl ether substitution is as follows.

<Alkyl etherification substitution degree>
(1) After putting 15 mg of a sample and 6 mL of hydroiodic acid in a decomposition flask, heat at 150 ° C. for 1 hour through nitrogen. The produced ethyl iodide is driven out to the gas phase, and then washed with a 1% by weight red phosphorus suspension and sent to an absorption tube. In the absorption tube, 15 g of potassium acetate is dissolved in 150 mL of a mixture of acetic acid / acetic anhydride (9/1), 145 mL of the solution is weighed, and 5 mL of bromine is added.
(2) Add the contents of the absorption tube to the stoppered Erlenmeyer flask containing the sodium acetate trihydrate solution. The contents adhering to the inner wall of the adsorption tube are washed out by adding water. Next, formic acid is added with shaking until the red color of bromine disappears.
(3) Add 3 g of potassium iodide and 15 mL of dilute sulfuric acid to the stoppered Erlenmeyer flask, stopper, shake lightly and leave for 5 minutes. The liberated iodine is titrated with a 0.1 mol / L sodium thiosulfate solution.
(4) First, the ethoxy group content (C _E ) is calculated from the following formula, and the alkyl etherification substitution degree (C _R ) of the present invention is calculated using this.
Ethoxy group content (C _E ) (%) = Titration (mL) × 75.10 / Sample amount (mg)
Alkyl etherification substitution degree (C _R ) (%) = 95 × C _E / (45-44C _E ) × 100

<Example 1>
In an autoclave reaction vessel, carboxymethylcellulose (carboxymethylation substitution degree 16.6%, number of carboxyalkyl group substituents per glucose ring unit 0.5) (A-1) 45.7 parts, sodium hydroxide (C-1) 20.8 parts, 1.8 parts of dimethyl coconut oil alkylbenzylammonium chloride (D-1), 80.5 parts of toluene, and 3.5 parts of water were added, and after nitrogen substitution, ethyl chloride ( B-1) 33.5 parts was gradually added and reacted for 12 hours. After completion of the reaction, the reaction product is transferred to a glass container, 215.9 parts of water and 13.3 parts of sulfuric acid are added, and the precipitated particles are washed with water and dehydrated with a centrifuge, dried at 90 ° C. under reduced pressure, and carboxymethyl ethyl cellulose. Got. The results are shown in Table 1.
In addition, “aggregation” indicating the appearance after completion of the alkyl etherification reaction in Table 1 indicates that there are many aggregates and a non-uniform state, and “solution state” indicates that these aggregates are absent, Indicates a uniform appearance.

<Example 2>
The same operation as in Example 1 was conducted except that 1.8 parts of dimethyldi-n-decylammonium chloride (D-2) was used instead of dimethyl coconut oil alkylbenzylammonium chloride (D-1) as a phase transfer catalyst in Example 1. .

< Reference Example 1 >
In Example 1, operation was carried out in the same manner as in Example 1 except that 1.8 parts of cetyltrimethylammonium chloride ( D′-4 ) was used instead of dimethyl coconut oil alkylbenzylammonium chloride (D-1) as the phase transfer catalyst.

<Comparative Example 1>
In Example 1, operation was carried out in the same manner as in Example 1 except that 1.8 parts of tetramethylammonium chloride (D′-1) was used instead of the phase transfer catalyst dimethyl coconut oil alkylbenzylammonium chloride (D-1).

<Comparative example 2>
In Example 1, operation was carried out in the same manner as in Example 1 except that 1.8 parts of trimethylbutylammonium chloride (D′-2) was used instead of dimethyl coconut oil alkylbenzylammonium chloride (D-1) as a phase transfer catalyst.

<Comparative Example 3>
In Example 1, it operated like Example 1 except having set it as 1.8 parts of tricoconut oil methylammonium chloride (D'-3) instead of the dimethyl coconut oil alkylbenzyl ammonium chloride (D-1) of a phase transfer catalyst. .

<Comparative example 4>
In Example 1, it operated like Example 1 except not having used a phase transfer catalyst.

As is clear from the above results, the production method of the present invention using a phase transfer catalyst having a specific chemical structure provides an alkyl etherified cellulose derivative having a high degree of alkyl ether substitution.
Moreover, since the uniformity after completion | finish of reaction is high and it becomes a solution state, handling becomes easy and the workability | operativity of a product separation and refinement | purification improves.

  The alkyl etherified cellulose derivative having a high degree of alkyl ether substitution obtained by the present invention is used for applications in which the solubility in water due to pH change and film forming ability are used. Usually, it can be used as an additive for drugs such as pharmaceuticals, particularly enteric coating agents, bitterness masking agents, or hair hair setting agents.

Claims (5)

An alkyl ether characterized by reacting cellulose or its derivative (A) with an alkylating agent (B) in the presence of an alkali (C) and a phase transfer catalyst (D) represented by the following general formula (1) For producing a modified cellulose derivative (E).
[Wherein R ¹ and R ² are each independently a linear aliphatic hydrocarbon group having 1 to 4 carbon atoms; R ³ is a nonyl group, a decyl group, a dodecyl group, a tetradecyl group, a hexadecyl group, an octadecyl group, An alkyl group composed of an oleyl group is represented. R ⁴ is a linear or branched aliphatic hydrocarbon group having 8 to 22 carbon atoms or an arylalkyl or arylalkenyl group having 7 to 22 carbon atoms; X ⁻ represents a monoanion of acid (F). ] The method for producing an alkyl etherified cellulose derivative according to claim 1, wherein R ⁴ in the general formula (1) representing the phase transfer catalyst (D) is an arylalkyl group having 7 to 22 carbon atoms. The method for producing an alkyl etherified cellulose derivative according to claim 1 or 2, wherein the acid (F) is an inorganic acid. The method for producing an alkyl etherified cellulose derivative according to any one of claims 1 to 3, comprising 0.1 to 20% by weight of (D) based on the weight of the cellulose derivative (A). The method according to any one of claims 1 to 4, wherein the cellulose derivative (A) is one or more selected from the group consisting of carboxyalkyl cellulose, hydroxyalkyl cellulose and alkyl cellulose.