The method of obtaining allobetulin

 

(57) Abstract:

The invention relates to the synthesis of allobetulin (19, 28-epoxy-oleana-3-ol) isomerization of Betulinol(loop-20(29)-ene-3, 28-diol) in the presence of catalysts. As the catalyst used is phosphoric acid, and the process is conducted by heating or in a solution of oxygen-containing solvents, with which the acid forms a homogeneous solution (homogeneous catalysis), or in a solution of hydrocarbons deposited on an inert carrier acid (heterogeneous catalysis). Mass fraction allobetulin in the isomerization product is 81-95%. For more clean allobetulin the isomerization product is recrystallized from ethanol, isopropanol, butanol, ethyl acetate. The proposed method allows to increase the yield of the target product, to facilitate the regeneration of the solvent and catalyst and to use the equipment of the conventional alloy steels. 2 C.p. f-crystals, 1 table.

The invention relates to the field of organic synthesis and chemical processing of biomass of birch wood and touches the synthesis allobetulin from Betulinol allocated from the extractives of the outer layer of birch bark (bark) or from byproducts of Solfatara is acyclic triterpenoid C30H50O2oleanolova number

,

like many other representatives of the triterpenoids, by itself or in the form of derivatives may be of interest to the pharmaceutical industry as a biologically active compound.

First isomerization of betulin in allobetulin made Schulze and Pyro in 1922 (Chem. Ber. , 1922, B. 55, S. 2322) processing Betulinol boiling 88% formic acid, followed by saponification of the resulting formate allobetulin potassium hydroxide, in the same two-stage scheme, through acyl derivative is education allobetulin when processing Betulinol acetic acid containing a catalytic amount of sulfuric acid /1/.

Possible one-step synthesis Betulinol - allobetulin under the influence of Hydrobromic acid in chloroform (Disehendorfen O., Monatshefte Chemie, 1923, B. 44, S. 23) or concentrated hydrochloric acid in ethanol /2/.

The method proposed by Schulze and Piro, complex, two-stage, when it is permanently lost formic acid on the formation of formate allobetulin and potassium hydroxide - on saponification formate.

Significant deficiencies have direct ways of isomerization (Dischendorfera'a and /2/), prinyesti - very strong acids, requiring equipment from expensive materials (PTFE, Nickel-molybdenum alloy, tantalum);

- regeneration of these acids from the reaction mixture is extremely difficult;

- and finally, when isomerization of Betulinol in the presence of chloride-hydrogen acid, along with allobetulin, with the release of about 20%, is formed by-product of isomerization - to 20.28-epoxy-19 H-Lupan - 3-ol /2/.

The aim of the invention is to increase the yield of the target product, technology simplification and cost reduction at the expense of refusal from the use of bromine - and chlorine-hydrogen acids and replaced them on slightly aggressive, easily regenerated and technological isomerization catalyst is phosphoric acid.

In the proposed method the isomerization process of Betulinol are in the presence of phosphoric acid when heated

or in a solution of oxygen-containing organic solvents, with which the phosphoric acid forms a homogeneous solution (homogeneous catalysis),

or in the solution of hydrocarbons deposited on an inert carrier phosphoric acid (heterogeneous catalysis).

As the oxygen-containing solvent in the homogeneous catalysis of esposti, distance.

As hydrocarbons in heterogeneous catalysis using aromatic and aliphatic hydrocarbons, xylene, octane, or a technical mixture of hydrocarbons with a boiling point above 110oC.

As a solid inert carrier for phosphoric acid using activated carbon, silica gel.

For more clean allobetulin, the isomerization product is subjected to recrystallization from ethanol, isopropanol, butanol, ethyl acetate.

Mass fraction of the main substances in Betulinol used in the experiments ranged between 95-97%.

Example 1 (prototype /2/). 0.33 g of Betulinol in a solution of 85 ml of ethanol mixed with 15 ml of concentrated chloride-hydrogen of the acid is heated in a flask under reflux for 5 hours. The reaction product obtained by evaporation of the ethanol from the reaction mixture under vacuum, Betulinol missing mass fraction allobetulin is 70,5%, the proportion of impurities and by-products is 29.5%.

In examples 2-9 (table. 1) the results of isomerization of Betulinol of the proposed method. The isomerization process is carried out in the reactor equipped with a reflux condenser. In the reactor for the t of the selected solvent. The isomerization product highlight several ways:

when homogeneous catalysis by filtering the crystals precipitated from the reaction mixture (method a), or by filtration, after removal of the solvent from the diluted reaction mixture (method "b");

- in the heterogeneous catalysis by removal of the solvent from liberated from the solid media reaction mixture (method "c").

The results of examples 2-9 for isomerization of Betulinol showed that in the presence of orthophosphoric acid

- achieved a high degree of transformation of Betulinol, the residual content in the reaction mixture does not exceed 2.7%, and in some experiments Betulinol becomes fully;

- provides good selectivity: mass fraction of impurities, excluding their content in the source Betulinol, does not exceed 15%, which is considerably lower than in the prototype, and mass fraction of the target product in some examples reaches 94%.

The use of phosphoric acid instead of galoidvodorodnykh acids will increase the yield of the target product, to facilitate regeneration of the solvent and catalyst and, finally, to use the equipment of the conventional alloy steels.

The method was verified in Labortechnik information

1. Barton D. H. R., Holness N. I. Triterpenoids. Part V. Some Relative Configuration in Rings C. D. and E. The Amirin and the Lupeol Group of Triterpenoids. / J. Chem. Soc., 1952, p. 78-92.

2. Errington, S. G., Chisalberti E. L., Jefferies, P. R. The Chemistry of The Euphorbiaceae. XXIV. Lup-20(29)-ene-3,16,28-triol from Beyeria var brevifolia. brevifolia./ Austr. J. Chem., 1976, 29, N 8, 1809-1814.

1. The method of obtaining allobetulin (19, 28-epoxy-oleana-3-ol) isomerization of Betulinol (loop-20(29)-ene-3, 28-diol) in an organic solvent in the presence of a catalyst, wherein the catalyst used is phosphoric acid.

2. The method according to p. 1, characterized in that in homogeneous catalysis as dioxane solvent used, either anhydrous or water-saturated N. butanol and Isobutanol.

3. The method according to p. 1, characterized in that in heterogeneous catalysis as a solvent used hydrocarbons (octane, xylene).

 

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11 cl, 1 tbl, 9 ex

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