CN1179431A - Process for manufacture of D-erythrose - Google Patents

Abstract

The invention relates to a process for the manufacture of D-erythrose, characterized in that an aqueous solution of a salt of gluconic acid is brought into contact with hydrogen peroxide in the presence of a salt of a metal selected from the group consisting of cobalt, nickel and ruthenium. It also relates to a process for the manufacture of erythritol by hydrogenation of D-erythrose thus obtained.

Description

The method for preparing the D-erythrose

The present invention relates to prepare the method for D-erythrose.

In particular, theme of the present invention is the method for preparing the D-erythrose from glyconic acid, and this method is with being selected from a kind of metal ion catalysis of cobalt, nickel and ruthenium and carrying out at aqueous phase.

The method for preparing the D-erythrose is known.

In these methods, can at first mention (Ber., 32,3674 (1899) by Ruff; 33,1799 (1900) methods that propose, it is included in aqueous hydrogen peroxide solution and participates in oxidation D-arabonic acid calcium down.The main drawback that a kind of like this method shows is to use arabonic acid as raw material, and arabonic acid is not a kind of product of conventional sale on market.

There is other to prepare the method for D-erythrose afterwards again, for example known oxidation D-glucose (Perlin A.S., MethodsCarbohydr.Chem., 1962 in the presence of lead tetraacetate with the name of Perlin method, 1,64), or by 4, the oxidizing reaction resulting 2 of the periodate of 6-O-ethylidene-D-glucose, acid hydrolysis (the Schaffer R. of 4-O-ethylidene-D-erythrose, J.Am.Chem.Soc., 81 (1959), 2838; Barker R. and MacDonald D.L., J.A.Chem.Soc., 82 (1960), 2301).

D-erythrose itself does not have very big value, if it can realize extensive and production cheaply, but can be a very important synthetic intermediate.

This is just can easily obtain tetrahydroxybutane because increase a hydrogenation D-erythrose stage simply, and this is a kind of polyvalent alcohol, can use in a lot of food applications, particularly can be as the non-dental caries of sucrose and the surrogate of low calory.

For this reason, another theme of the present invention is the method for preparing tetrahydroxybutane from the D-erythrose that the method according to this invention obtains.

Though tetrahydroxybutane is widespread in nature and just constitute the part of human foods from period in time immemorial, tetrahydroxybutane is ignored by foodstuffs industry circle for a long time always, obtains tetrahydroxybutane because be difficult to the method for economy.

In pharmaceutical industries, tetrahydroxybutane can be oxidized to the L-erythrulose, and this is a kind of molecule with good functionality, and this good functionality can be given the possibility that it uses in biologically active cpds is synthetic.

Research prepares the method for tetrahydroxybutane, sees on the whole, is divided into two main routes: chemosynthesis and fermenting organism are synthetic.

But these known chemical synthesising technologies, for example reduce mesotartaric acid salt, oxidation/reduction 4,6-O-ethylidene-D-glucose and hydrogenated starch dialdehyde hydrolyzate (T.Dola and T.Sasaki, Bio-Industry, (1988), 5, (9), 32), none can reach real technical scale.

Although the research of fermentation technique is more much more than the research of chemosynthesis, fermentation technique only relates to the production as the tetrahydroxybutane of less important formation thing in most of situations.

These researchs are devoted to adopt Debaryomyces (US-A2 986 495)/Pichia (US-A2 986 495), Candida (US-A3 756 917), Moniliella (Antonie vanLeeuwenhoek, 37 (1971), 107-118) and Aureobasidium (Jp-A61/31 091) yeast method produce tetrahydroxybutane.

Yet the result of tetrahydroxybutane fermentation method research has recently announced some shortcomings, for example during fermentation produces the speed of foam, fermentation, content and the especially low-yield of byproduct, and the latter has further endangered its industrialized possibility.

Therefore have a kind of demand, need a kind of method of producing the D-erythrose efficiently of exploitation (thereby producing tetrahydroxybutane by the hydrogenation of the D-erythrose that obtains like this), this method does not have the limitation and the shortcoming of prior art.

When carrying out this exercise question research, the application company has developed a kind of novel method that adopts chemical route to produce the D-erythrose from glyconic acid or its esters just.This method of the present invention has been got back to again on the principle of the method that is proposed by Ruff before a nearly century.

This method can by means of the acting in conjunction of iron ion and aqueous hydrogen peroxide solution, make the glyconic acid that contains n carbon atom be converted into the aldose that contains (n-1) individual carbon atom with general approach.But the productive rate of aldose is very low.

But, glyconic acid is converted into the D-arabinose carries out according to this method.

Some improve successively by R.C.Hockett and C.S.Hudson (J.Amer.Chem.Soc., 56,1632-1633, (1934) and ibidem 72,4546 (1950)) and US-A3 755 294 patents proposition.Wherein described from glyconic acid initially, the arabinose productive rate is 60%.Finished this improvement by using cupric ion (Cu (II)) as catalyzer by V.Bilik (CZ-232647, (1983)).After the purifying of effort, reach about 70% productive rate.

Use the mixture of ferric iron and ferrous ion to obtain same result recently as catalyzer (CZ-279002, (1994)).

At last, under specific conditions, patent EP-A0 716 067 has reported the productive rate of aldose 78%.

The application company has made us finding uncannily in to the broad research of Ruff reaction, and reacting what obtain with cobalt, nickel and the catalytic glyconic acid of ruthenium salt and aqueous hydrogen peroxide solution is the D-erythrose, rather than the D-arabinose of always being thought.The raw material glyconic acid has lost two carbon atoms like this, relatively.

Therefore, according to the present invention, the method for preparing the D-erythrose is characterised in that, in a kind of presence of salt of the metal that is selected from cobalt, nickel and ruthenium, a kind of aqueous solution of gluconate contacted with hydrogen peroxide.

Compared with former fermentation process, first advantage of this method obviously is that it has avoided the restricted and problem relevant with above-mentioned fermentation technique.

Second advantage of the method according to this invention is that it implements extremely easily, because raw material and reagent all obtain easily.

The 3rd advantage of the method according to this invention is that the D-erythrose is to obtain near stoichiometric extraordinary productive rate.

Another advantage of the method according to this invention is that it is easy to be applied in the industry, especially in the foodstuffs industry, because it makes water as solvent, no matter be with regard to toxicity or with regard to regard to the security, this is an admittedly advantage.

Method of the present invention is used gluconate.

In the present invention, gluconate be interpreted as free form glyconic acid, lactone form or with form, the form of salt or the form of ester of the mixture of these two kinds of forms.Therefore, for example calcium gluconate, gluconic acid sodium salt and δ-glucono-lactone are to be suitable for fully.

Glyconic acid obtains by oxidizing glucose with known method.The chemical route that both can adopt this oxidation stage also can adopt the microorganism route to carry out.

Preferred route is included in and uses air or oxygen in the alkaline medium and use the palladium catalyst oxidizing glucose in content of the present invention.

A particularly preferred method is the method for having described in U.S. Pat-A4 845 208 (the application company is the transferee of this patent), and this method comprises uses the palladium be attached on the gac and be doped with bismuth as oxide catalyst.

Also it is contemplated that and adopt the electrolysis route or use the hypobromite oxidizing glucose.Can also adopt the microorganism route to use Gluconobacter or Aspergillus bacterium oxidizing glucose.

Method of the present invention is 1-60%, preferred 5-50% and more preferably carry out in the water of 10-30% in the concentration of gluconate (dry-matter) preferably.

The lower limit of regulation dry-matter is because aspect vaporize water and reduce the economic cause of aspect of the size of reactor significantly.

The upper limit of dry-matter is mainly limited by reaction mixture solubility or viscosity problem.

In this manual, all per-cent is all represented (for example: 50% mole of X is meant the X of 50 moles of per 100 moles of glyconic acids, and 50%X is meant the X of every 100g raw material glyconic acid 50g) with respect to glyconic acid.

In the method according to the invention, catalyzer is that the ion by the metal that is selected from cobalt, nickel and ruthenium constitutes, and these ions can be estimated according to any divalence or trivalent, the form of the salt of nickel and ruthenium adds.The preferred cobalt salt that uses: for example the halogenide of cobaltous acetate, acetopyruvic acid cobalt, cobalt, Xiao Suangu, rose vitriol etc. are all suitable fully.

For employed gluconate, the amount of catalyzer (cobalt, nickel or ruthenium salt) is 0.001-50%, preferred 0.002-20%, and more preferably 0.005-5%, no matter the D-erythrose that obtains in the method according to the invention all obtains good result on the productive rate or on purity.

Then, with hydrogen peroxide, it preferably is the form of 30% aqueous hydrogen peroxide solution with concentration, under agitation slowly join in the mixture of gluconate, catalyzer and water, in the gluconate that uses, the ratio of hydrogen peroxide is the 1-500% mole, preferred 50-400% mole, more preferably 100-300% mole.

Can be with concentration greater than 30% form, especially for example concentration is used aqueous hydrogen peroxide solution up to 70% form.

The speed that aqueous hydrogen peroxide solution adds will make the temperature of reaction mixture rise and preferably be no more than 50 ℃, more preferably no more than 35 ℃.Therefore, aqueous hydrogen peroxide solution adds speed usually between 30 minutes to 2 hours.

Method of the present invention is preferably carried out under 0-100 ℃ temperature, more preferably 10-50 ℃.

Lower temperature too prolongs the reaction times, and higher temperature also can make reactor product produce degraded except requiring to use the measuring body reactor.

Therefore, the particularly preferred temperature of method of the present invention is 20-40 ℃.

Be 2-12 preferably at pH, preferably at 5-8, more preferably carry out method of the present invention at 6-7.

The D-erythrose that is rough form that obtains according to the present invention is catalytic hydrogenation at an easy rate subsequently.

A kind of like this hydrogenation of sugar is to carry out according to the rule of this area, and these rules are from the method that for example generates sorbyl alcohol from glucose.

In this stage, both ruthenium-based catalyst can be used, also the Raney nickel catalyzator can be used.

But preferably use comparatively cheap Raney catalyzer.

In fact, in as dry-matter treat hydrogenant sugar, use the catalyzer of 1-10% weight.Being 15-50% at dry matter content preferably, in the slurry of 30-45%, is to carry out hydrogenation under the 20-200 crust at hydrogen pressure more preferably.Can carry out continuously, or carry out in batches.

When carrying out hydrogenation, used hydrogen pressure is the 30-60 crust in batches, and the temperature of carrying out hydrogenation is 100-150 ℃.Be also noted that by for example adding sodium hydroxide or yellow soda ash and keep the pH value of hydrogenation mixture, but do not make the pH value surpass 9.0.Carrying out hydrogenation in such a way can avoid cracking or isomerization product to occur.

The content of reducing sugar becomes less than 1% in reaction mixture, preferably less than 0.5%, be more preferably less than 0.1% o'clock stopped reaction.

After the reaction mixture, remove by filter catalyzer, the D-tetrahydroxybutane desalination to obtaining like this by negatively charged ion and resin cation (R.C.).

In this stage, contain at least 90% D-tetrahydroxybutane in the slurry, after concentrating and cooling off this solution, be easy to purification D-tetrahydroxybutane from this slurry by crystallization.

To understand the present invention better by following embodiment, the unique purpose of these embodiment is in order to specify the present invention better, rather than wants to limit the invention to embodiment and the employed single calcium gluconate of specially describing.

All results represent with molar percentage in the following example.

Embodiment 1:

With the calcium gluconate monohydrate (115.7g, 0.255mol), cobalt chloride hexahydrate (0.58g, 2.4mmol) and water (1000ml) be added in the reactor that has chuck.

With this mixture heating up to 30 ℃, and the pH value is adjusted to 6.5 with the sodium hydroxide solution of 2N.

(130ml 1.28mol) remains on temperature 30-35 ℃ simultaneously, and adding 2N sodium hydroxide solution remains on 6.5 with the pH value to add aqueous hydrogen peroxide solution in 70 minutes.

Adding after aqueous hydrogen peroxide solution finishes, with solution restir one hour.By adding the vitriol oil (14ml) pH is transferred between the 2.5-3, so that the precipitation calcium salt.

After the filtration, peach solution has following composition: D-erythrose (87%), D-arabinose (2%) and glyconic acid (7%).

The per-cent that provides is corresponding to analytical results.Its summation is not equal to 100, because sometimes form a spot of arabonic acid (2%) and other byproduct.

These byproducts are: formic acid, " carbonate " and carbonic acid gas.

Embodiment 2:

With the calcium gluconate monohydrate (115.7g, 0.25mol), cobalt chloride hexahydrate (2.24g, 9.5mmol) and water (1000ml) join in the reactor that has chuck.With this mixture heating up to 40 ℃, and use the sodium hydroxide solution of 2N that the pH value is adjusted to 6.5.(95ml 1.1mol) remains on temperature 40-45 ℃ simultaneously, and adding 2N sodium hydroxide solution makes the pH value remain on 6.5 to add 35% aqueous hydrogen peroxide solution in 70 minutes.After hydrogen peroxide add to finish, with solution restir 3 hours.By adding the vitriol oil (14ml) pH is transferred to 2.5, so that the precipitation calcium salt.After the filtration, green solution has following composition: D-erythrose (40%) and glyconic acid (45%).

The per-cent that provides is corresponding to analytical results.Its summation is not equal to 100, because also form Glycerose (6%) and arabinose (2%).

Reaction by-product is: formic acid and carbonic acid gas.

Claims (9)

1. prepare the method for D-erythrose, it is characterized in that, the aqueous solution with a kind of gluconate under a kind of salt that is selected from the metal of cobalt, nickel and ruthenium participates in contacts with hydrogen peroxide.

2. according to the described method for preparing the red glucose of D-of claim 1, it is characterized in that the content as the gluconate of dry-matter of the described aqueous solution is 1-60%.

3. according to any described method for preparing the D-erythrose in claim 1 and 2, it is characterized in that in described gluconate, the described metal-salt amount that is selected from cobalt, nickel and ruthenium is 0.001-50%.

4. according to any described method for preparing the D-erythrose in the claim 1 to 3, it is characterized in that used hydrogen peroxide preferably is the form of 30% aqueous hydrogen peroxide solution with concentration, is the 1-500% mole in its consumption of salt of glyconic acid.

5. according to any described method for preparing the D-erythrose in the claim 1 to 4, it is characterized in that, be reflected under the 0-100 ℃ of temperature and carry out, preferred 10-50 ℃.

6. according to any described method for preparing the D-erythrose in the claim 1 to 5, it is characterized in that, be reflected between the pH value 2-12 and preferably between 5-8, carry out.

7. according to any described method for preparing the D-erythrose in the claim 1 to 6, it is characterized in that, described gluconate by use air or oxygen, in alkaline medium, oxidizing glucose obtains under palladium catalyst participates in.

8. according to any described method for preparing the D-erythrose in the claim 1 to 6, it is characterized in that described gluconate adopts microorganism route oxidizing glucose to obtain.

9. prepare the method for tetrahydroxybutane by hydrogenation D-erythrose, it is characterized in that, described D-erythrose is to adopt method any among the claim 1-8 to obtain.