JPH0248594A - Production of d-glucofuranose or d-xylofuranose - Google Patents

Abstract

PURPOSE:To obtain the title high-purity compound useful as a synthetic intermediate for spice substance in high yield simply and inexpensively by a specific method using chloro-di-O-isopropylidene-alpha-D-glucofuranose as a raw material. CONSTITUTION:6-Chloro-1,2:3,5-di-O-isopropylidene-alpha-D-glucofuranose as a raw material shown by formula I is catalytically reduced in the presence of a reduction catalyst (e.g., Raney nickel) to give D-glucofuranose among the aimed compound shown by formula II or the compound shown by formula I is reacted with 1,8-diazabicyclo [5,4,0]-7-undecene and catalytically reduced in the presence of the reduction catalyst to give D-xylofuranose among the aimed compound shown by the formula II. The above-mentioned D-xylofuranose is a novel substance.

Description

Detailed Description of the Invention (Industrial Field of Application) The present invention provides furaneol (2,5
A novel method for producing D-glucofuranose or D-xylofuranose derivatives which can be used as intermediates for the synthesis of dimethyl-3-hydroxy-4-oxo-4,6-cyhydrofuran) is developed.

More specifically, the present invention relates to 6-dioxy-1,2:3.5-di-0-isopropylidene-α-D-gluco represented by the following formula (1) -1 included in the following formula (1). Furanose or wire type (
5-C- represented by the following formula (1)-2 included in 1)
Methyl-1,2:3.5-di-0-isopropylidene-
This invention relates to a new method for producing α-D-xylofuranose.

(Prior art) Conventionally, from 6-chloro-1,2:3.5-di-0-isopropylidene-α-D-glocofuranose of formula (2) above, D- Glucofuranose or D
- There is no known method for synthesizing xylofuranose derivatives.

On the other hand, regarding the synthesis of a related compound (E) that can be used as a synthetic intermediate for furaneol, for example, the synthesis method shown in the reaction process diagram below is known (New Experimental Chemistry Course m1
4-5.2485, 1978).

(A) CB) Futaneol According to the reaction method in the above reaction process diagram, D of the above formula (A)
- forming an isopropylidene derivative of formula (B) from glucose and reacting linear formula (B) with benzaldehyde in the presence of zinc chloride to synthesize an acetal of formula (C);
Next, react the linear formula (C) compound with tosyl chloride in the presence of lysine to obtain a tosyl derivative of formula (D), and then reduce the linear formula (D) compound with lithium aluminum hydride to lead to Furaneol. A compound of formula (E) has been synthesized.

(Problems to be Solved by the Invention) As mentioned above, in the conventional proposals for producing analogous compounds (E) that can be used as synthetic intermediates for furaneol, the reaction steps are long and the reaction operations are complicated. There are problems such as low yield and unsuitability for industrial implementation. In addition, when Furaneol is synthesized from the above formula (E) compound, the yield is low, and the linear formula (E) compound is Furaneol.
ne.

There are disadvantages that make it unsuitable for use as an intermediate in the synthesis of l.

(Means for Solving the Problems) The present inventors have conducted intensive research to avoid the disadvantages and drawbacks described above.

As a result, the above formula (1)-1 was synthesized using 6% formula (2), which can be easily synthesized manually or from monoglucose in the market, using the shortened process using %redene-α-D-glucofuranose as a raw material. It has been discovered that the compound can be industrially advantageously synthesized with high yield and simple operations. or,
5-C-Methyl-1゜2:3,5-di-O-isopropylidenefuranose of the above formula (1)-2, which is a new compound not previously described in the literature, can be synthesized from the above formula (2) compound in two steps. It was also discovered that it can be synthesized industrially with high yield and easy operation.

That is, the present inventors discovered that 6- expressed by the following formula (2)
Chloro-1,2:3,5-di-0-isopropylidene-
The above formula (
It has been discovered that 6-dioxy-1,2:3,5-di-0-isopropylidene-α,D-glucofuranose represented by the following formula (1)-1, which is included in 1), can be synthesized.

Alternatively, the above formula (2) compound is reacted with 1,8-diazabicyclo[5,4,01-7-undecene in an organic solvent to form 5,6-dihydro-1,2 represented by the following formula (3). :3,5-G-O
-isopropylidene-α-D-glucofuranose and then the compound of linear formula (3), e.g. in an organic solvent,
Therefore, the object of the present invention is to obtain the following formula (1)-2 which is included in the above formula (1) by carrying out a catalytic reduction reaction in the presence of a reduction catalyst. The compound is represented by the above formula (2)
The object of the present invention is to provide a new method that enables industrial production of compounds with high purity and low cost through easy operations.

The mode of production of the above formula (1) compound of the present invention is described by the above formula (
2) When shown in a process diagram including manufacturing examples of the compound, it can be expressed as follows. Also shown is a method for synthesizing furaneol from the compound of formula (1) above.

5-C-methyl-1,2:3,5-di0- represented by
It has been discovered that isopropylidene-α-D-xylofuranose can also be synthesized.

(b) The above formula (1) included in the above formula (1) compound of the present invention
-1 of 6-dioxy-1,2:3.5-di-O-isopropylidene-α-D-glucofuranose and the above formula (
1) The method for producing 5-C-methyl-〇-xylopyranose of -2 will be explained in detail below according to the above process diagram.

6-chloro-1,2:3,5 of the above formula (2) as a starting material
-di-0-isopropylidene-α-D-glucofuranose can be easily obtained by reacting D-glucose of formula (5) in the presence of zinc chloride and sulfuric acid to easily obtain 1 of formula (4).
,2:5,6-di-0-isopropylidene-α,D-glucofuranose can be derived from the following linear equation (4)
The compound of formula (2) can be easily synthesized by reacting the compound in dimethylformamide in the presence of methanesulfonyl chloride, for example.

For example, in order to synthesize the above formula (1)-1 compound from the formula (2) compound that can be synthesized as described above, the formula (
2) It can be easily synthesized by subjecting the compound to a catalytic reduction reaction in the presence of a reduction catalyst. The reaction conditions include, for example, hydrogen pressure of about 60 to 130 Kg/cm2;
A more preferable range is approximately 80 to 110 kg/cm2. Further, the reaction temperature is, for example, about 506C to 120C, preferably about 709C.
The zero reaction time, which can be in the range of about 100"C, varies depending on the above conditions, but for example, about 8 hours to 100"C.
A preferable example of the reaction time is a range of about 20 hours.

Examples of the reduction catalyst used in the above reaction include Raney nickel and palladium carbon. The amount of such a catalyst to be used is not particularly limited and may be selected as appropriate, but it can be used, for example, in a range of about 2 to 10% based on the compound of formula (2). Further, the reaction is preferably carried out in an aS-containing medium, and examples of such organic solvents include ethanol, methanol, and the like. There is no particular restriction on the amount of these 8N-containing solvents to be used, and they can be used in a wide range of ways.
2) A range of approximately 1 to 50 times the volume of the compound can be exemplified. The above catalytic reduction reaction may be carried out in the presence of an alkali such as potassium hydroxide or sodium hydroxide, if desired. After the reaction is completed, the catalyst used is removed and the solvent is distilled off, e.g. Highly pure formula (1)-1 can be obtained by purification with column chromatography.

In addition, the above formula (1)-2 included in the above formula (1) compound
To synthesize 5-C-methyl-1,2:3,5-di-0-isopropylidene-α-D-xylofuranose,
First, the above formula (2) compound is dissolved in, for example, an organic solvent with 1.8-
React with diazabicyclo[5,4,01-7-undecene to obtain the above formula % -s. Then, the compound of formula (3) is subjected to a catalytic reduction reaction in, for example, an organic solvent in the presence of a reduction catalyst. Accordingly, the compound of formula (1)-2 can be easily synthesized.

The amount of 1,8-diazabicyclo[5,4,O]-7-undecene used to synthesize the compound of formula (3) is, for example, about 1-1 with respect to the compound of formula (2).
A preferable example is a range of about 0 mol. Further, examples of the organic solvent to be used include solvents such as tetrahydrofuran, dioxane, and diethyl ether. The usage of these solvents includes:
Although there is no particular limit and the amount can be selected as appropriate, a preferred example is a range of about 1 to 60 times the weight of the compound of formula (2).

This reaction can be carried out, for example, in a temperature range of about 10° to 90°C and for a reaction time of about 1 to 50°C. After the reaction is completed, the oil layer is separated by washing according to a conventional method. After concentration, the formula (
3) A compound can be obtained.

The catalytic reduction reaction of the compound of formula (3) that can be obtained as described above can be carried out, for example, at a hydrogen pressure of about 5 to 60 Kg/cm2.
range of degrees, more preferably about 10 to 30 Kg/cm2
The reaction can be carried out within a range of N degrees and for a reaction time of about 1 to 8 hours. Examples of the catalyst used in this reaction include Raney nickel, palladium-carbon, and Raney cobalt. The amount of these catalysts to be used can be selected as appropriate, but for example, formula (3)
A preferable example is about 0.1 to 20% by weight of the compound. In addition, examples of the 8N solvent used include hexane, ethyl acetate, methanol,
Examples include solvents such as ethanol. The amount of these organic solvents used may be selected appropriately, but for example, the formula (3
) After the completion of the reaction, the catalyst is removed, concentrated, and purified by column chromatography, for example, to easily obtain the compound of formula (1)-2. can be obtained. Thus, formula (1)-1 and formula (1) can be synthesized as described above.
The -2 compound can be easily converted into furaneol, which is useful as a perfume material, as shown in the process diagram above.

Below, several aspects of the present invention will be explained in more detail by giving reference examples and examples.

(Reference example) (1) 1,2:5,6-di-0-isopropylidene-α
, D-glucofuranose formula (4).

85% phosphoric acid 7 in D-glucose 150g (0.83 mol), acetone 10100O, ZnCj2 120g
．． After adding 5 g of the mixture and reacting at room temperature for 30 hours, the mixture was cooled to -10°C, stirred for 1 hour, and unreacted D-glucose was collected under reduced pressure. The filtrate was cooled and neutralized by dropping 170 g of a 50% aqueous sodium hydroxide solution at 0 to 5°C. The resulting salt was separated under reduced pressure, and the filtrate was concentrated, leaving a residual aroma of 150 m
Add water from step 1 and extract with chloroform (150ml x 3) L
/, the chloroform layer was washed with 100 ml of water, dried over magnesium sulfate, and concentrated to give 11
5g was obtained. The crude crystals were recrystallized using 230 g of n-hexane and 3 g of ethyl acetate to obtain compound 96 of formula (4).
I got glt. (yield near 0%) (2) 6-chloro-1,
2: 3,5-di-O-isopropylidene-α-D-glucofuranose formula (% formula % Formula (4) 15.6 g (59.9 mmol) and 150 ml of dry dimethylformamide were charged, and methanesulfonyl chloride 13. 8g (120,5 mmol)
was added and reacted at 90°C for 6 hours. After the reaction was completed, the reaction solution was poured into ice-cooled aqueous sodium bicarbonate solution/ether, the oil layer was separated, the aqueous layer was extracted with ether, the oil layers were combined, and the mixture was diluted with sodium sulfate. After drying and concentration, column chromatography (toluene/ethyl acetate = 9/
1) Purification was performed to obtain 13.03g (78,
1%) was obtained.

(Example) (1) 6-dioxy-1,2:3,5-di〇-isopropylidene-α,D-glucofuranose formula % formula % formula (2) compound 8.5 g (30.5 mmol), 99% ethanol 400 in which 2.1g of potassium hydroxide was dissolved
m1. Raney nickel Ig was charged into an autoclave and reacted at 85°C and hydrogen pressure of 100 kg/cm2 for 15 hours. After removing the catalyst and distilling off the solvent, column chromatography was performed using 500 g of silica gel (toluene/ethyl acetate = 9575 ) to purify the compound of formula (1)-1 to 5
-43 g (72.8% yield) was obtained.

(2) Synthesis of 5,6-dihydro-1,2:3,5-di-0-isopropylidene-α-D-glucofuranose formula (3).

47.4 g (0.17 mol) of formula (2) compound, 150 ml of tetrahydrofuran, 1,8-diazabicyclo[5
A solution of 77.7 g (0.51 mol) of ,4,0-7-undecene was reacted under reflux for 8 hours. After the reaction, the solvent was distilled off, 300 ml of ether was added to the residual aroma, and the mixture was washed with water.
% hydrochloric acid aqueous solution and sodium bicarbonate aqueous solution, dried over magnesium sulfate, and purified by column chromatography (toluene/ethyl acetate = 9/1) using I kg of silica gel to obtain 28.46 g of the compound of formula (3) ( Yield 6
9%).

(3) 5-C-methyl-1,2:3,5-G〇-α-
Synthetic formula (3) compound of D-xylofuranose formula (1) -2 8-5 g (35.5 mmol), n-hexane 9
0ml 1.5% palladium-carbon 2g was charged into an autoclave, hydrogen pressure 10Kg/cm2.401C~5
A catalytic reduction reaction was carried out under conditions of 0°C, and after the completion of the reaction, the catalyst was removed, the solvent was distilled off, and the residual aroma was purified by column chromatography (toluene/ethyl acetate = 9/1) using 500 g of silica gel. 1)-2 compound 7.61g (yield 87.
9%) obtained.

(Reference example) (3) 6-zooxy-D-glucobylanose formula (% formula % formula (1)-1 compound 3.85 g (15.8 mmol)
, 30 ml of water, and 151.0 g of Amberlyst-150 were reacted at 50°C for 57 hours. After the reaction, the resin was removed and concentrated under reduced pressure to obtain the crude compound of formula (a) 3.
．． 36g was obtained. This was subjected to column chromatography (chloroform/methanol = 4/1) using 150 g of silica gel.
) Purification to obtain 2.38g of the compound of formula (a) (
92.0% yield) was obtained.

(4) Synthesis of furaneol formula (b).

Formula (a) compound 2.38 g (14,5 m')% le)
After adding 714 mg of veridine and 1.19 g of acetic acid to a solution of 20 ml of 99% ethanol at room temperature, the mixture was reacted under heating under reflux for 8 hours. After the reaction was completed, the mixture was cooled and concentrated under reduced pressure to obtain 4.1 g of crude product. Obtained. This was purified by column chromatography (hexane/ethyl acetate: 2/1) using 76 g of silica gel to obtain 1.32 g of the compound of formula (b) (71.0% yield).
I got it.

(Effects of the Invention) According to the present invention, furaneol (2,5-dimethyl-3-hydroxy-4oxo-
It is possible to provide a method that can advantageously synthesize D-glucofuranose or D-xylofuranose derivatives represented by the following formula (1), which can be used as synthetic intermediates for 4,5-dihydrofuran), using a completely new manufacturing method. .

Claims (1)

[Claims] 1. 6-chloro-1,2:3,5-di-0-isopropylidene-α represented by the following formula (2) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (2) -D-glucofuranose is subjected to a catalytic reduction reaction in the presence of a reduction catalyst or reacted with 1,8-diazabicyclo[5,4,0]-7-undecene,
A method for producing D-glucofuranose or D-xylofuranose derivatives represented by the following formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(1), which is characterized by carrying out a catalytic reduction reaction in the presence of a reduction catalyst. .