JP2010053038A - Method for producing alkyl-etherified saccharide - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of producing an alkyl-etherified saccharide wherein asymmetrical dehydration etherification selectively and highly efficiently proceeds without cutting a sugar chain. <P>SOLUTION: The method of producing the alkyl-etherified saccharide comprises subjecting a saccharide and a compound having a hydroxy group in its molecule to dehydration condensation in the presence of a catalyst and a solvent in carbon dioxide in a supercritical state. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a method for producing an alkyl etherified product of saccharides. More specifically, a dehydration condensation reaction between the saccharide (A) and the compound (B) having a hydroxyl group in the molecule in the supercritical carbon dioxide (E) in the presence of the catalyst (C) and the solvent (D). The present invention relates to a method for producing an alkyl etherified product (F).

Conventionally, a method for producing an ether compound by dehydration condensation between alcohols is known to have been performed under high temperature (180 ° C. or higher) and acid catalyst conditions (Bronsted acid and Lewis acid). Examples of the Bronsted acid include sulfuric acid and hydrochloric acid.
Known Lewis acids include halogenated transition metal acids such as AlCl ₃ ; and super Lewis acids such as B (C ₆ F ₅ ) ₃ and Al (C ₆ F ₅ ) ₃ .

  The above-mentioned method for producing an ether compound by dehydration condensation between alcohols is used for a method for producing a symmetrical ether compound (for example, diethyl ether or dibutyl ether) between the same alcohols (for example, Patent Document 1).

  On the other hand, the method for producing an asymmetric ether compound by dehydration condensation between different alcohols is limited. Specifically, a selectivity of 90% or more is realized only between the primary alcohol and the tertiary alcohol (for example, Non-Patent Document 1), but usually when the primary alcohol and the secondary alcohol are used. Has no selectivity and results in a mixture of three types of alkyl ethers.

  As an alternative reaction, an asymmetric ether compound is generally produced using an alkylating agent (for example, dialkyl sulfate ester, dialkyl carbonate, alkyl chloride) and an alcohol as raw materials. For example, methylated sucrose synthesis from a sucrose derivative and dimethyl sulfate ester (for example, Non-Patent Document 2), a method for methylating mercerized cellulose with methyl chloride (for example, Patent Document 2), and the like can be mentioned.

  However, the method for producing an asymmetric ether compound using an alkylating agent requires a desalting step, and the trouble becomes more remarkable particularly in application to saccharides having a high molecular weight and a small amount of good solvent. Therefore, as a means for eliminating the desalting step, a direct dehydration condensation reaction between saccharides and alcohols is used. However, conventional techniques such as sulfuric acid treatment require a high temperature of 180 ° C. or higher, and the sugar chain bond is degraded. Furthermore, the method for producing a dehydrated condensed ether compound using a primary alcohol or a secondary alcohol results in a complicated reaction system in which three types of ether are mixed. It is difficult to obtain a compound with high selectivity.

  As a conventional method for producing an ether compound by dehydration, a reaction system using a Bronsted acid (for example, sulfuric acid or p-toluenesulfonic acid) as a catalyst can be mentioned. A high temperature of 180 ° C. or higher is necessary. Breakage of the chain bond occurs as a side reaction.

JP-A-11-158102 JP-A-10-152502 Chemical Communication, 2003, 1054-1055 Carbohydrate Research, 1991, 218, 237-245

  The present invention relates to a method for producing an alkyl etherified product of a saccharide, wherein the sugar chain is not cleaved and a highly selective asymmetric dehydration etherification proceeds with a high degree of substitution. The purpose is to provide.

The inventors of the present invention have reached the present invention as a result of studies to achieve the above object.
That is, the present invention relates to a method for producing an alkyl etherified product (F) of a saccharide (A), in the presence of a catalyst (C) and a solvent (D) in carbon dioxide (E) in a supercritical state. A method for producing an alkyl etherified product (F), which comprises subjecting A) and a compound (B) having a hydroxyl group in the molecule to a dehydration condensation reaction.

The method for producing an alkyl etherified product of saccharides of the present invention has the following effects.
(I) Since it is a method for producing an ether compound by dehydration condensation between alcohols, a desalting step is not required.
(Ii) Since it is a method for producing an ether compound using a supercritical fluid, it is not particularly necessary to go through a purification step, and the content of the symmetric etherified product by condensation of the same type alcohol as a by-product is reduced to 1% by weight or less. Is possible.
(Iii) Since it is a method for producing an ether compound using a supercritical fluid, the activation energy of the reaction is reduced, and the reaction can be performed at a lower temperature (40 to 120 ° C.) than the conventional (180 ° C.), It does not involve side reactions such as sugar chain cleavage.
(Iv) Since it is a method for producing an ether compound using a Lewis acid as an acid catalyst, sugar chain cleavage is suppressed by about 80% compared to Bronsted acid.
(V) In the case of a method for producing an ether compound using super Lewis acid as an acid catalyst, the acid catalyst may be a catalytic amount.

  In the present invention, a saccharide (A) and a compound (B) having a hydroxyl group in the molecule are subjected to a dehydration condensation reaction in supercritical carbon dioxide (E) in the presence of a catalyst (C) and a solvent (D). This is a method for producing an alkyl etherified product (F).

  In the present invention, the raw material saccharide (A) is not particularly limited, and may be a saccharide having an unsubstituted hydroxyl group or a saccharide having a hydroxyl group partially substituted by alkyl etherification or carboxymethylation. .

Examples of the saccharide having an unsubstituted hydroxyl group include monosaccharides (eg, glucose, fructose, galactose, etc.) or disaccharides (eg, trehalose, maltose, sucrose, etc.) (A1); polysaccharides (eg, cotton, wood-derived pulp, bacteria) Cellulose such as cellulose, lignocellulose, and regenerated cellulose; chitosan, chitin, microorganism-produced polysaccharides, etc.) (A2) and the like.
Preferred are glucose, fructose, galactose, trehalose, maltose, and sucrose, cellulose, chitosan, chitin, and particularly preferred are trehalose and cellulose.

  Examples of saccharides in which a hydroxyl group is partially substituted include etherified products of saccharides (for example, ethyl trehalose, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, etc.), and esterified products of saccharides (for example, trehalose acetate, cellulose acetate, Cellulose lactate, cellulose butyrate, cellulose acetobutyrate, cellulose capronate, etc.), cellulose ether esters (for example, hydroxypropyl cellulose lactate, hydroxyethyl cellulose butyrate, etc.) and the like.

  The type of the compound (B) having a hydroxyl group in the molecule as another raw material in the present invention is not particularly limited, but is preferably a monovalent aliphatic or araliphatic alcohol having 1 to 18 carbon atoms. It may be selected according to the target cellulose derivative. From the viewpoint of reactivity and product selectivity, more preferred are methanol, ethanol, benzyl alcohol, propylene glycol, ethylene glycol and the like.

  When a Bronsted acid (for example, sulfuric acid, p-toluenesulfonic acid, etc.) is used as the catalyst (C) for the dehydration condensation reaction in the present invention, the sugar chain bond breakage occurs as a side reaction. Therefore, Lewis acid (C1) is preferable as the catalyst (C). However, an ordinary Lewis acid is deactivated with the generated water, and therefore an equivalent amount is required.

Accordingly, a Lewis acid having both durability against nucleophilic attack and thermal stability is more preferable because it exhibits an effect even in a small amount. A Lewis acid having both durability against such nucleophilic attack and thermal stability is generally called a super Lewis acid (C2).
Examples of the super Lewis acid (C2) include a Lewis acid having a perfluorophenyl group (hereinafter abbreviated as C ₆ F ₅ ) or a trifluoromethanesulfonic acid group (hereinafter abbreviated as Tf) in its chemical structure ( C21), hafnium tetrahalide (C22) and the like.

  Examples of the super Lewis acid (C21) include a silicon compound (C211) represented by the following general formula (1), a complex compound (C212) represented by the following general formula (2), and the like.

R represents an aliphatic hydrocarbon group having 1 to 4 carbon atoms, and examples thereof include a methyl group and an ethyl group.
Y represents a nitrogen atom, a carbon atom, a sulfur atom, an oxygen atom or a phosphorus atom.
Z represents a perfluorophenyl group _(C 6 _{F 5)} or trifluoromethanesulfonic acid (Tf).
m represents the number of Y, and is an integer of 1 to 3. n is an integer of 1-4.

M represents an aluminum atom, a scandium atom, or a boron atom.
Y represents a nitrogen atom, a carbon atom, a sulfur atom, an oxygen atom or a phosphorus atom.
Z represents C ₆ F ₅ or Tf.
j and k are integers of 1 to 3.

As the silicon compound (C211), Me ₃ SiNTf ₂ and (C ₆ F ₅ CTf ₂ ) SiMe ₃ are preferable.
Examples of the complex compound _{(C212), B (C 6} F 5) 3, Al (C 6 F 5) 3, Sc (NTf 2) 3, Sc (OTf 3) 3, Sc (CTf 3) 2 is preferred .

  As the above-mentioned hafnium tetrahalide (C22), a hafnium compound represented by the following general formula (3) is preferable.

X ^{1 to} X ⁴ are each independently a halogen atom.
For example, tetrachlorohafnium, dibromodichlorohafnium, and the like can be given. Preference is given to tetrachlorohafnium.

  The amount of super Lewis acid used in the present invention is preferably from 0.1 mol% to 10 mol%, more preferably from 0.5 mol% to 1 mol%, based on the hydroxyl group of the saccharide.

In the method for producing an alkyl etherified product (F) of a saccharide of the present invention, a dehydration condensation reaction is carried out in the presence of a solvent (D).
(1) A case where a monosaccharide or disaccharide (A1) is dissolved in the solvent (D1) in advance using the solvent (D1) and then subjected to a dehydration condensation reaction;
(2) The polysaccharide (A2) may be swollen in advance in the swelling agent (D2) using the swelling agent (D2) and then subjected to a dehydration condensation reaction.

The solvent (D1) in the monosaccharide and disaccharide (A1) of the present invention is preferably a solvent that dissolves 1 g or more of the saccharide with respect to 100 g of the solvent, and examples thereof include dimethyl sulfoxide (DMSO), water, and ionic liquid. It is done.

With respect to the polysaccharide (A2), a solvent having excellent solubility is limited, and the use condition of the solvent is also special (for example, a copper ammonia solution), so that it is difficult to use a normal solvent. However, in the present invention, it is not necessary to use a homogeneous solution system, and the reaction proceeds sufficiently by the swelling treatment with the swelling agent.
For the above reasons, it is preferable to use the swelling agent (D2) for the polysaccharide (A2). As the swelling agent (D2) in the polysaccharide (A2) of the present invention, 1 g of the polysaccharide is used per 100 g of the solvent. A swelling agent that swells above is preferable, and examples thereof include N-methylmorpholine oxide, ionic liquid, DMSO, water, toluene, and ethylenediamine.
As a swelling treatment method for the polysaccharide (A2) of the present invention, a method in which the polysaccharide is swollen in advance in the swelling agent (D2) before the reaction is preferable.

The method for producing an alkyl etherified product (F) of a saccharide of the present invention comprises subjecting a saccharide (A) and a compound (B) having a hydroxyl group in the molecule to a dehydration condensation reaction in carbon dioxide (E) in a supercritical state. Features.
The supercritical carbon dioxide (E) in the present invention refers to a compressible fluid that is found when conditions of a critical temperature (31.0 ° C.) and a critical pressure (7.4 MPa) are satisfied. Furthermore, a supercritical fluid is defined as a non-condensable fluid that exceeds the gas-liquid critical temperature and pressure inherent to the substance.
The thermal motion of the molecule is intense because it exceeds the critical temperature, and the density can be continuously changed by changing the pressure from a dilute state close to the ideal gas to a high-density state corresponding to the liquid. .

  Further, by using a supercritical fluid, it becomes possible to design a reaction system at a lower temperature (120 ° C. or lower) than a normal high temperature reaction (180 ° C. or higher). The first reason is that the transition state of the reaction system is stabilized and the activation energy is lowered, and the second reason is that the saccharide (A) has a penetrating action on the sugar chain skeleton.

  The supercritical carbon dioxide (E) in the production method of the present invention preferably has a temperature of 40 to 120 ° C. and a pressure of 10 to 20 MPa.

  The reason why carbon dioxide was used as the fluid in the supercritical state in this study is to promote the formation of the alkyl etherified product (F) by the dehydration condensation reaction because carbon dioxide in the supercritical state is a Lewis acidic field. Nitrogen in a supercritical state does not have an effect of promoting such a reaction.

  The temperature during the reaction in the present invention is in the supercritical region temperature range of carbon dioxide, and is preferably 31 ° C. to 180 ° C., more preferably 40 ° C. to 120 ° C. from the viewpoint of side reactions such as sugar chain decomposition.

  The pressure during the reaction in the present invention is in the supercritical region pressure range of carbon dioxide, and is preferably 7.4 to 30 MPa, more preferably 10 to 20 MPa from the viewpoint of reaction rate, side reaction, and simplicity of the apparatus. .

  The reaction time in the present invention may be adjusted according to the reaction temperature, but is preferably from 0.1 to 20 hours, more preferably from 0.3 to 20 hours from the viewpoint of productivity.

  The degree of substitution (DS) of the alkyl etherified saccharide (F) of the present invention is 0 to 2.5.

  Moreover, content of the salt and organic solvent in said alkyl etherified saccharide (F) is 100 ppm or less, and is a high purity alkyl etherified saccharide. Moreover, it is also possible to make it 50 ppm or less by increasing the frequency | count of extraction with the supercritical carbon dioxide (E) after reaction.

The reaction rate of the alkyl etherified saccharide (F) is measured by the following method.
<Measurement method of reaction rate of alkyl etherified saccharide (F)>
Hydroxyl value before and after reaction according to 7.3 pyridine-acetyl chloride method of JIS K0070: 1992 “Testing method for acid value, saponification value, ester value, iodine value, hydroxyl value and unsaponified product of chemical products” Is obtained from the following equation.
Reaction rate (%) = (hydroxyl value after alkylation / hydroxyl value before alkylation) × 100

The decomposition rate (sugar chain cleavage rate) of the alkyl etherified saccharide (F) is measured by the following method.
<Measurement method of decomposition rate>
The average molecular weight is measured by GPC and is obtained from the following formula.
Decomposition rate (%) = (Actual average molecular weight after alkylation / Theoretical molecular weight after alkylation) × 100

The selectivity of the alkyl etherified saccharide (F) is measured by the following method.
<Selectivity measurement method>
It is obtained from the following equation by actual measurement of the weight of the alkyl etherified saccharide (F) and the symmetric alkyl etherified product (G) after separation by the CO2 flow.
Selectivity (%) = F / (F + G) × 100
F: Weight of alkyl etherified saccharide (g)
G: Weight of symmetric alkyl ether compound (g)

  Hereinafter, although an example and a comparative example explain the present invention further, the present invention is not limited to these.

(Example 1) Ethyl etherification of trehalose After 3.7 g of trehalose dihydrate (molecular weight 378.3) was dissolved in 30 g of DMSO, 180 g of ethanol and 0.05 g (1 mol%) of perfluorotriphenylborane were added, A 300 mL capacity high pressure resistant kettle was charged.
After the temperature was raised to 45 ° C., liquefied carbon dioxide was pumped in to set the inside of the reaction kettle to 18 MPa. After stirring for 8 hours, the mixture was cooled to 35 ° C., and liquefied carbon dioxide was pumped in, and the reactor was degassed from different valves so that the internal pressure of the reaction kettle was constant at 18 MPa (hereinafter referred to as flow). Perfluorotriphenylborane and unreacted ethanol were recovered.
When the product flowed sufficiently and the product was dried, 4.2 g of the intended ethyl trehalose (A-1) (reaction rate 77% based on the raw sugar) was taken out from the reaction kettle.
The content of diethyl ether, which is a symmetric ether as a by-product, and the ether condensate between sugar chains was analyzed by NMR. It was 0.12 g (content 3% based on the product) of diethyl ether (G-1) and 0 g (concentration 0%) of a condensate of sugar chains (G-2).

(Example 2) Ethyl etherification of cellulose In Example 1, 3.7 g of cellulose powder (average molecular weight 5000) was used instead of trehalose dihydrate and swollen with 30 g of DMSO, which was the same as Example 1. Operation was performed to obtain 4.2 g (reaction rate: 40%) of the target ethyl cellulose (A-2). In addition, it was 0.11 g (content rate 3%) of diethyl ether (G-3) and 0 g (content rate 0%) of the condensate of sugar chains (G-4).

(Comparative Example 1) Ethyl etherification of trehalose (reaction in supercritical nitrogen)
In Example 1, except that liquefied carbon dioxide was used as liquefied nitrogen and reacted in nitrogen in a supercritical state, the same operation as in Example 1 was performed, and unreacted raw trehalose (A′-1) 7 g (reaction rate 0%) was recovered.

(Comparative Example 2) Ethyl etherification of trehalose (reaction without solvent)
In Example 1, except that neither a solvent such as DMSO nor a swelling agent was used, the same operation as in Example 1 was performed, and 3.7 g (reaction rate 0%) of unreacted raw material trehalose (A′-2) was performed. Then, 0.12 g of diethyl ether (G′-3) and 0 g of a condensate of sugar chains (G′-4) were obtained.

(Comparative Example 3) Ethyl etherification of trehalose (conventional reaction with Bronsted acid catalyst)
In Example 1, except that 0.01 g (1 mol%) of sulfuric acid was used instead of perfluorotriphenylborane, the same operation as in Example 1 was performed, and a decomposition product of trehalose (ethyl glucose) (A′-3 ) 5.2 g (reaction rate 7%), diethyl ether (G′-5) 0.15 g (content rate 3%), and sugar chain (G′-6) condensate 0 g (content rate 0%). It was.

The reaction rate (%), decomposition rate (%), and selectivity (%) described in Table 1 were calculated based on the above-described calculation formula. The results are shown in Table 1.
In Comparative Examples 1 and 2, since the raw material was unreacted (reaction rate 0%), the selectivity could not be measured.

As is clear from Table 1,
Both the monosaccharide example 1 of the present invention and the polysaccharide example 2 have a sufficiently high reaction rate and a very high selectivity (the content of the symmetric etherification product is 3% by weight or less).
On the other hand, in Comparative Example 1 using nitrogen as a supercritical fluid, the reaction did not proceed, and in Comparative Example 2 using no solvent or swelling agent for saccharides, the reaction did not proceed.
Further, in Comparative Example 3 using Bronsted acid sulfuric acid as a catalyst, although the reaction itself proceeded, all of the trehalose was decomposed into glucose units.

The alkyl etherified saccharide of the present invention is extremely useful as a pharmaceutical because the content of the symmetric etherified product (G) is 5% by weight or less and exhibits an excellent high purity. It can also be used in cosmetics, pH-dependent agricultural chemicals, binders for electronic materials, building materials, and the like.

Claims (10)

  In the method for producing an alkyl etherified product (F) of a saccharide, a compound having a saccharide (A) and a hydroxyl group in the molecule in carbon dioxide (E) in a supercritical state in the presence of a catalyst (C) and a solvent (D) A method for producing an alkyl etherified product (F), which comprises subjecting (B) to a dehydration condensation reaction.   The process for producing an alkyl etherified product according to claim 1, wherein the catalyst (C) is a Lewis acid (C1).   The method for producing an alkyl etherified product according to claim 2, wherein the Lewis acid (C1) is a super Lewis acid (C2). The Lewis acid (C21) in which the super Lewis acid (C2) has a perfluorophenyl group (hereinafter abbreviated as C ₆ F ₅ ) or a trifluoromethanesulfonic acid group (hereinafter abbreviated as Tf) in its chemical structure Or a method for producing an alkyl etherified product according to claim 3, which is hafnium tetrahalide (C22). The alkyl ether according to claim 4, wherein the super Lewis acid (C21) is a silicon compound (C211) represented by the following general formula (1) or a complex compound (C212) represented by the following general formula (2). Method for producing chemicals.

[R is an aliphatic hydrocarbon having 1 to 4 carbon atoms; Y is a nitrogen atom, a carbon atom, a sulfur atom, an oxygen atom, or a phosphorus atom; Z represents C ₆ F ₅ or Tf. m is an integer of 1 to 3, and n is an integer of 1 to 4. ]

[M is an aluminum atom, scandium atom or boron atom; Y is a nitrogen atom, carbon atom, sulfur atom, oxygen atom or phosphorus atom; Z is C ₆ F ₅ or Tf; j and k are integers of 1 to 3] is there. ]   The method for producing an alkyl etherified product according to any one of claims 1 to 5, wherein the compound (B) is a monovalent or divalent aliphatic or araliphatic alcohol.   The saccharide (A) is a monosaccharide or disaccharide (A1) selected from the group consisting of glucose, fructose, galactose, trehalose, maltose and sucrose, or a polysaccharide (A2) selected from the group consisting of cellulose, chitosan and chitin The method for producing an alkyl etherified product (F) according to any one of claims 1 to 6.   Using a solvent (D1) that dissolves 1 g or more of the saccharide (A1) in 100 g of the solvent (D), the saccharide (A1) is dissolved in the solvent (D1) in advance, and then subjected to a dehydration condensation reaction. 8. The method for producing an alkyl etherified product according to claim 7,   Using a swelling agent (D2) that swells 1 g or more of the polysaccharide (A2) with respect to 100 g of the solvent (D), the polysaccharide (A2) is previously swollen in the swelling agent (D2), and then dehydrated and condensed. It reacts, The manufacturing method of the alkyl ether compound (F) in any one of Claim 7 characterized by the above-mentioned.   Content of symmetrical etherification product (G) obtained by the method for producing alkyl etherification product (F) according to any one of claims 1 to 9, and by condensation between the compounds (B) and condensation between the saccharides (C) Alkyl etherified product (F) whose amount is 5% by weight or less.