JPH07278171A - Production of 3-o-alkyl-1,2;5,6-di-o-isopropylidene-d-glucofuranose - Google Patents

Abstract

PURPOSE:To produce the subject compound of high purity in a high yield. CONSTITUTION:In production of a 3-O-alkyl-1,2; 5,6-di-O-isopropylidene-D- glucofuranose by etherifying 1,2 ;5,6-di-O-isopropylidene-D-glucofuranose, this production method is carried out by reacting 1,2; 5,6-di-O-isopropylidene-D- glucofuranose with an etherifying agent in the presence of an alkaline substance and a catalyst composed of a quaternary onium salt.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The present invention makes it possible to obtain sugar ether compounds, which are important as surfactants, raw materials for medicines, raw materials for cosmetics, etc., in a high yield.
It relates to a method for producing 5,6-di-O-isopropylidene-D-glucofuranose.

[0002]

2. Description of the Related Art Conventionally, polyhydric alcohols and their esters and ethers have been widely used as raw materials or products for producing detergents, foods, industrial chemicals, pharmaceuticals and the like. Among these polyhydric alcohols, sorbitan fatty acid esters derived from sorbitol, which is one of sugar alcohols, and ethylene oxide adducts thereof, and sucrose fatty acid esters derived from sucrose, which is one of disaccharides, are pharmaceuticals. , It is particularly useful in a wide range of fields such as cosmetics and food [eg oil chemistry, No. 16
Vol., Pp. 395-401 (1967), etc.]. Further, a sugar alcohol, which is a disaccharide in which a linear monosaccharide and a monocyclic monosaccharide are ether-bonded, has been applied to a cosmetic base as a moisturizing agent [eg, Fragrance Journal, No. 14,
86-93 (1975), etc.]. Furthermore, since octyl-β-D-glucoside derived from D-glucose, which is one of the typical monosaccharides, is effective as a solubilizing agent for protein membranes, it can be applied to pharmaceutical bases and the like. It has been reported [eg, Biochemistry, Vol. 20, p. 7776 (1981)]. Similarly, it is disclosed that a series of derivatives obtained by alkylating the 3-position of the D-glucose skeleton using D-glucose as a raw material is effective as an antitumor agent (for example, JP-A-56-56). No. 103196, etc.). Furthermore, it is also known that 3-O-dodecyl-D-glucose can be used as a general surfactant [eg,
Tenside Detergents, Volume 15, 72-74 (1978)].

The present inventors have focused their attention on the above-mentioned usefulness of polyhydric alcohols, especially saccharides,
We have been conducting research on the utilization of sugars that are abundant in nature, especially monosaccharides. As a part of the results, mannitol, which is one of the chain monosaccharides useful as a cosmetic base, has been reported as mono- and dialkyl mannitol (Japanese Patent Publication 6).
No. 4-7061) is proposed.

Glucose monoalkyl ether known as such a monocyclic sugar ether compound, especially 3-O-
3-O-alkyl-1,2; 5,6-di-O-isopropylidene-as an intermediate for the production of alkyl glucose
D-glucofuranose is an industrially important sugar ether. Such 3-O-alkyl-1,2; 5,6-di-O
Examples of the method for producing isopropylidene-D-glucofuranose include 1,2; 5,6-di-O-isopropylidene-D-glucofuranose in a solvent having a high dielectric constant such as dimethyl sulfoxide and dioxane. , In the presence of organic halogen compounds and a large excess of alkaline substances, 10
A method of reacting at 0 to 160 ° C (for example, JP-A-49-
No. 134616, No. 51-118714),
Alternatively, a method of reacting with an alkali metal hydride in the presence of an organic halogen compound (for example, Chem.Pharm.Bull.35 (7),
2894-99 (1978), Arzneim.-Forsch./Drug Res. 29 (II), 986
-90 (1979)] is known.

[0005]

However, in these conventional methods for producing sugar ethers, (1) a special organic solvent having a high dielectric constant such as dimethyl sulfoxide or dioxane must be used, (2) A large excess of alkaline substances must be used, a large amount of wastewater treatment, etc. are required, (3) harsh conditions must be set so that the reaction temperature exceeds 100 ° C, and energy consumption is large ( 4) It was difficult to carry out industrially because there was a problem that dangerous chemicals such as alkali metal hydride had to be used.

Accordingly, the object of the present invention is to provide 3-O-alkyl-1,2,5,3 as a useful sugar ether compound which can produce a high-purity sugar ether with high yield simply and industrially.
It is intended to provide a method for producing 6-di-O-isopropylidene-D-glucofuranose.

[0007]

Under these circumstances, the inventors of the present invention have conducted diligent research and as a result, in the presence of an alkaline substance and a quaternary onium salt, 1,2; 5,6-di-O-
By reacting isopropylidene-D-glucofuranose with an etherifying agent, 3-O-alkyl-1,2; 5,6
The present invention was completed by finding that -di-O-isopropylidene-D-glucofuranose can be efficiently obtained.

That is, the present invention is to etherify 1,2; 5,6-di-O-isopropylidene-D-glucofuranose to give 3-O-alkyl-1,2; 5,6-di-
In the method for producing O-isopropylidene-D-glucofuranose, 1,2; 5,6-di-O-isopropylidene-D-glucofuranose and an etherifying agent are quaternized in the presence of an alkaline substance. 3-O-alkyl-1, characterized by reacting onium salt as a catalyst,
The present invention provides a method for producing 2,5,6-di-O-isopropylidene-D-glucofuranose.

The production method of the present invention can be carried out, for example, according to the following reaction formula.

[0010]

[Chemical 1]

(In the formula, R represents a linear or branched alkyl group or alkenyl group having 1 to 24 carbon atoms, and X represents a halogen atom, a sulfonic acid group or a sulfuric acid group)

That is, 1, 2 represented by the formula (2);
5,6-di-O-isopropylidene-D-glucofuranose (hereinafter, referred to as "glucofuranose diacetonide (2)"
And an etherifying agent represented by RX are reacted in the presence of an alkaline substance and a quaternary onium salt to give a 3-O— represented by the general formula (1).
It is possible to obtain alkyl-1,2; 5,6-di-O-isopropylidene-D-glucofuranose (hereinafter sometimes referred to as "3-O-alkylglucofuranose diacetonide (1)").

The glucofuranose diacetonide (2) used here can be obtained, for example, by using glucose as a raw material and reacting it with an excess amount of a dehydrating agent such as acetone and sulfuric acid.

Examples of the etherifying agent used in the present invention include alkyl halides, alkyl sulfonates,
Examples thereof include alkyl sulfate ester. Of these, alkyl halides are preferable, and alkyl chloride, alkyl bromide, and alkyl iodide are particularly preferable.

The hydrocarbon group R contained in these etherifying agents (RX) may be a linear or branched alkyl group or alkenyl group having 1 to 24 carbon atoms, preferably 8 to 20 carbon atoms. . Specific examples of such a hydrocarbon group include octyl, dodecyl, decyl, cetyl, stearyl, oleyl and other linear alkyl groups or alkenyl groups, 2-ethylhexyl, 2-heptylundecyl,
5,7,7-trimethyl-2- (1,3,3-trimethylbutyl) octyl, the following formula;

[0016]

[Chemical 2]

(In the formula, m represents an integer of 4 to 10, n represents an integer of 5 to 11, m + n represents 11 to 17, and has a distribution having vertices at m = 7 and n = 8. ), And branched-chain alkyl groups such as methyl-branched isostearyl.

These etherifying agents are preferably used in an amount of 1 to 10 mol, and particularly preferably 1.5 to 3.0 mol, per 1 mol of glucofuranose diacetonide (2).

The alkaline substance used in the present invention includes:
Examples thereof include alkali metal hydroxides, alkali metal carbonates, alkali metal phosphates, alkaline earth metal hydroxides, alkaline earth metal carbonates and alkaline earth metal phosphates. Among these, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and alkaline earth metal hydroxides such as calcium hydroxide are preferable.
These alkaline substances are 10-80%, especially 40-6.
It is preferably used as a 0% aqueous solution, but may be used as a solid.

These alkaline substances are preferably used in an amount of 1 to 10 mol, particularly 2 to 5 mol, and more preferably 1.5 to 3 mol, per 1 mol of glucofuranose diacetonide (2).

Examples of the quaternary onium salt used in the present invention include a quaternary ammonium salt and a quaternary phosphonium salt. Among them, the quaternary ammonium salt is easily available industrially, Is preferred. Examples of the quaternary ammonium salt include tetrabutylammonium bromide, tetrabutylammonium hydrogensulfate, trioctylmethylammonium chloride, lauryltrimethylammonium chloride, stearyltrimethylammonium chloride and other tetraalkylammonium salts; tetraoxyethylenestearyldimethylammonium chloride. , Alkylammonium salts having a polyoxyalkylene group such as bistetraoxyethylenestearylmethylammonium chloride; betaine compounds, crown ethers, amine oxide compounds, ion exchange resins and the like.

Further, as the quaternary phosphonium salt,
Wherein; [R ¹ R ² R ³ PR ^{4] +} X ^- represented by those in the like. Specific examples of this quaternary phosphonium salt include those of the following groups (a) to (c). In the formula (a), R ¹ represents an aralkyl group having 7 to 10 carbon atoms or a higher alkyl group having 8 to 20 carbon atoms, and R ² , R ³ and R ⁴ represent a lower alkyl group having 1 to 6 carbon atoms. thing. For example, benzyl tributyl phosphonium salt, stearyl tributyl phosphonium salt, hexadecyl tributyl phosphonium salt, lauryl tributyl phosphonium salt, etc. can be mentioned.

In the formula (b), 2 to ⁴ of R ¹ , R ² , R ³ and R ⁴ represent a cycloalkyl group having 5 to 8 carbon atoms, and the balance is an alkyl group having 1 to 20 carbon atoms. Or carbon number 7-
Those showing 10 aralkyl groups. For example, dicyclohexyldimethylphosphonium salt, tricyclohexylmethylphosphonium salt, tricyclohexylethylphosphonium salt, tricyclohexyl n-butylphosphonium salt, tricyclohexylisobutylphosphonium salt, tricyclohexyl n-propylphosphonium salt, tricyclohexylisopropylphosphonium salt, tricyclohexylamyl Phosphonium salt, tricyclohexylhexylphosphonium salt, tricyclohexylheptylphosphonium salt, tricyclohexyldecylphosphonium salt, tricyclohexyllaurylphosphonium salt, tricyclohexyltetradecylphosphonium salt, tricyclohexylhexadecylphosphonium salt, tricyclohexylstearylphosphonium salt, tricyclohexyl Benzyl phosphonium salt, and tetra-cyclohexyl phosphonium salts.

(C) For example, tetramethylphosphonium salt, tetraethylphosphonium salt, methyltripropylphosphonium salt, diethyldibutylphosphonium salt, dibenzylbutylmethylphosphonium salt, dibenzyldimethylphosphonium salt, tetrabutylphosphonium salt, dibenzylethylmethyl. Examples thereof include phosphonium salt, dibenzyldiethylphosphonium salt, tribenzylmethylphosphonium salt, tribenzylethylphosphonium salt, and tri-n-butylethylphosphonium salt.

[0025] In the above (a) ~ (c), the phosphonium salt ^- in X ([R ¹ R ² R ³ PR ^{4] +} X) ^- represents an organic or inorganic ion, such as halogen ions (Cl
^- , Br ⁻ , I ⁻ ), hydroxide ion (OH ⁻ ), nitrate ion (NO ₃ ⁻ ), hydrogen sulfate ion (HSO ₄ ⁻ ), and the like.

These quaternary onium salts are added in an amount of 0.01 to 0. 0 per mol of glucofuranose diacetonide (2).
It is preferable to use 20 moles, particularly 0.05 to 0.10.
Molar is preferred.

The reaction of glucofuranose diacetonide (2) with the etherifying agent is carried out in a solvent under heating, preferably with stirring. The solvent used here is not particularly limited as long as it does not participate in the reaction, for example, hexane, heptane, aliphatic hydrocarbons such as octane, cyclopentane, alicyclic such as cyclohexane Examples thereof include hydrocarbons, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether, tetrahydrofuran, diglyme and dioxane. The reaction temperature is preferably 25 to 80 ° C, and 4
The temperature is more preferably 0 to 60 ° C., and the etherification is completed in a few hours to a dozen hours by vigorous stirring. After completion of the reaction, the product can be separated and purified according to a usual method such as a distillation method.

[0028]

According to the production method of the present invention, 3-O-alkyl-1,2; 5,6, which is a sugar ether industrially important, is used.
-Di-O-isopropylidene-D-glucofuranose can be obtained with high purity and high yield. Further, a general solvent or an alkaline substance can be used, and the amount of the alkaline substance used is small, so that economical and time burden can be reduced. Furthermore, since the reaction can be performed under mild temperature conditions of 50 ° C. or less, the reaction operation is easy.

[0029]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited thereto.

Production Example 1 Production of 1,2; 5,6-di-O-isopropylidene-D-glucofuranose: In a 5 liter reaction vessel equipped with a reflux condenser, a thermometer, a dropping funnel and a stirrer. D-Glucose (200 g) and acetone (4 liter) were charged, and the mixture was vigorously stirred under ice cooling. Then, 160 ml of 97% concentrated sulfuric acid was added dropwise from the dropping funnel over about 1.5 hours. The temperature of the reaction mixture was maintained at 5-10 ° C during the dropwise addition of sulfuric acid. After completion of dropping, stirring was continued at room temperature for about 5 hours. The temperature of the reaction mixture rose to 20-25 ° C and the color of the solution changed from yellow to pale orange. Subsequently, a 50% aqueous sodium hydroxide solution (245 g of NaOH / 245 ml of water) was used to slowly neutralize the reaction mixture, taking care not to raise the temperature suddenly. After the completion of neutralization, the mixture was allowed to stand overnight to precipitate salts and unreacted D-glucose. The precipitated white solid was filtered off and the pressure was reduced to remove the acetone in the filtrate. The pale yellow syrup-like substance obtained was added to 300 ml of chloroform.
After being dissolved in water and washed twice with 150 ml of water, chloroform was distilled off again by concentration under reduced pressure to obtain a pale yellow solid. This solid was recrystallized from cyclohexane to obtain 120 g of the title compound as white crystals (yield 42%). The melting point of this compound is 111-112 ° C. [reference value (Method i
n Carbohydrate Chem.Vol.II, 320-322,1963): 110
C.].

Example 1 Preparation of 3-O-octyl-1,2; 5,6-di-O-isopropylidene-D-glucofuranose: reflux condenser,
In a 1 liter reaction vessel equipped with a thermometer, a dropping funnel and a stirrer, 48 g of 50% sodium hydroxide aqueous solution (N
aOH 24 g (0.6 mol) / water 24 ml), Production Example 1
1,2; 5,6-di-O-isopropylidene-D obtained in
-Glucofuranose 52.1 g (0.2 mol), n-hexane 180 ml, 50% tetrabutylammonium hydrogen sulfate aqueous solution 13.6 g (0.02 mol) were charged in this order, and stirred at 20 to 25 ° C in a water bath. did. Then, from the dropping funnel, n-octyl bromide 57.9 g (0.3
0 mol) was added dropwise over about 1.5 hours. After the dropping is completed,
The temperature of the reaction mixture was raised to 50 ° C., and the mixture was stirred at this temperature at a stirring rate of about 400 rpm for about 5 hours. 1, 2 of raw materials from the reaction mixture by gas chromatography;
After confirming the disappearance of 5,6-di-O-isopropylidene-D-glucofuranose, the mixture was cooled to room temperature,
400 ml of water was added and the mixture was allowed to stand, and the reaction mixture was separated into two layers. The organic layer was taken out, washed with 100 ml of water, and then n-hexane was distilled off under reduced pressure, followed by distillation under reduced pressure to obtain 70.9 g of the title compound as a colorless transparent oily substance (yield 95 %).

B. p. 154 ° C./0.3 mmHg Elemental analysis: C 67.4%, H 10.6% (calculated value: C 67.3%, H 10.6%) 1 H-NMR (δ ppm): C ₁ -H 5 _{.77 (d) C 3 -OC H} 2 3.48 (t) IR: 3000,2940,2860,1380,13
70, 1215, 1165, 1075, 1020, 85
0.

Examples 2 to 7 Using 1,2; 5,6-di-O-isopropylidene-D-glucofuranose obtained in Production Example 1 under the conditions of the etherifying agent and the reaction time shown in Table 1, Each sugar ether compound was produced in the same manner as in Example 1. The yield of these compounds,
Table 1 also shows elemental analysis values and the like. The etherifying agent used in Example 6 was produced according to the production method described in JP-B No. 64-7061, page 6, column 11 and reference example 2.

[0034]

[Table 1]

Claims (4)

[Claims] 1. An etherification of 1,2; 5,6-di-O-isopropylidene-D-glucofuranose to give 3-O.
-Alkyl-1,2; 5,6-di-O-isopropylidene-D-glucofuranose
1,3-O-isopropylidene-D-glucofuranose, 1,2; -Alkyl-1,2; 5,6-di-O
-Method for producing isopropylidene-D-glucofuranose. 2. The 3-O-alkyl-1,2,5,6-di-O-isopropylidene-group according to claim 1, wherein the alkaline substance is selected from alkali metal salts and alkaline earth metal salts. A method for producing D-glucofuranose. 3. The 3-O-alkyl- according to claim 1, wherein the quaternary onium salt is a quaternary ammonium salt.
A method for producing 1,2; 5,6-di-O-isopropylidene-D-glucofuranose. 4. The 3-O-alkyl according to claim 1, wherein the etherifying agent is a linear or branched alkyl chloride, alkyl bromide or alkyl iodide having 1 to 24 carbon atoms. -1,2; 5,6-di-O-isopropylidene-D-glucofuranose production method.