DE217559C - - Google Patents

Description

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IMPERIAL

PATENT OFFICE.

PATENT LETTERING

- «Μ 217559 CLASS 12 q. GROUP

GEORG R. GRASSER and Dr. KARL PURKERT

In Graz.

the Betula alba.

Patented in the German Empire on November 27, 1907.

The present invention relates to a process for converting the water-insoluble resin acid contained in the leaves of Betula alba from the empirical composition C ₄₀ H ₇₀ O ₅ into water-soluble alkali salts of a higher molecular acid.

When processing natural resin substances, oxycarboxylic acids and their hydrogen atoms are obtained are substitutable by alkali.

ίο The action of alkali on the alcoholic solution of the resin acids can neutralize both the hydrogen of the carboxyl groups and that of the hydroxyl groups with the formation of the corresponding phenolates. If the bodies obtained in this way are now treated in alcoholic solution with dry carbonic acid, this carbonic acid can be added by substituting the hydrogen atoms of the aromatic radical with carboxyl groups. The acid C ₄₀ H ₇₀ O ₅ , whose formula according to the inventors' investigations in:

^ C ₃₃ H ₆₅ O ₂ ) - C ₆ H ₉ (OH) - (COO H)

is to be dissolved, this first goes into the alkali salt:

(C _ss H ₆₅ O ₂ ). C ₆ H ₃ (O Me). (COO Me)

and finally delivers the double salt when exposed to carbonic acid

(C _m H ₆₅ O ₂ ) • C ₆ H ₂ (O Me) - (COO Me) ₂ + 2MeHCO ₂ .

Mineral acids convert this double salt into free resin acid "

(C ₃ , H ₆₅ O ₂ ) -C ₆ H ₂ - (OH) - (COO H) ₂

disassembled. Alcoholic alkali transforms the acid into the general alkali salts Formula:

^ C ₃₃ H ₆₅ O ₂ ) - C ₆ H ₂ . (O Me). (COO M) ₂

regressed. The analysis of the potassium salt gave figures that were correct _{for the formula C 41} H ₆₇ O ₇ K _3.

To produce the starting material, the dried and crushed ones are treated Birch leaves, which, in order to give the extraction liquid the largest possible attack surface offer, are intimately mixed with pebbles, in an extraction apparatus for so long with alcohol, until the green parts of the plant have become noticeably lighter. This lightening namely occurs only at the moment when all of the resin has dissolved. One hears now expediently with the further extraction, because otherwise more difficult to dissolve plant substances would pass into the alcoholic solution. However, this should be avoided because the subsequent cleaning of the desired end product is made more difficult by the inclusion of further substances would. The impure resin-acid solution obtained in this way is then filtered while still hot and, if necessary, diluted with alcohol until that a half-saturated solution is formed.

500 g of alcoholic extract are obtained from looo g of air-dried leaves, and this contains 100 g of tannins and bitter substances, 25 g of dyes and chlorophyll, 55 g of acid C ₄₀ H _n O ₅ , 20 g of resinotannol C ₃₉ H ₆₈ O ₅ .

Analytical evidence for the formula C ₄₀ Ii ₇₀ O ₆ :

i. Elementalysis.

0.1541 g H ₂ O 0.4508 g C O ₂ \

0.1561 g H ₂ 0.4543 g C ° 2

0.1614 g of substance
0.1623 g of substance

0.1777 g of substance

2. Determination of molecular weight (increase in boiling point). Solvent: sulfur ether K = 2160

° ' ¹⁷⁶³ = 76.3 percent C ; 10.7 percent H. = 76.3 percent C; 10.7 percent H.

0.1693 g H ₂ O) _ _{7βτ percent c} . _{IOj7 percent} #

M ₁ = 2160 ■

0.016 13.6 = 6o8, M ₂ = 2160. -

0.055 13.6

_{= 622} ,

Assume C ₈ H ₁₄ O :

percent Calculated Found Percent C 76.2 76.2 Percent H 11.1 10.7 Mol. G. v. [C ₈ F ₁₄ O] ₅ 630 a) 608 b) 622

3. Determination of the carboxyl and hydroxyl groups.

theoretically found

C ₄₀ # 70 O ₅ = 630

Example.

,, I for neutralization: 38.8 g, 38.2 g K, need “., ■, ^J ° J ₀ , _T ?

for saponification: 77.6 g, 76.8 g if,

hence: C ₃₉ H ₆

COOH

The alcoholic extract from birch leaves is refluxed for 4 hours with the calculated amount of potassium hydroxide (39g KOH 10% per 1000 g drug). Here, the alkali first neutralizes the carboxyl groups of the acid and, after this process has essentially been completed, substitutes the hydrogen of the phenol group. Long boiling is inappropriate because it can cause rapid decomposition of the reaction product formed. After the alkali has acted, the solution obtained is filtered hot from the separated decomposition products and pure, well-dried carbonic acid gas is introduced in a strong stream with stirring and shaking, initially with a gentle supply of heat. Once the condensation starts, there is another

Heat supply is not necessary, as sufficient heat is released by the reaction that occurs. At the same time, the condensation product, which is insoluble in alcohol, separates out.

The introduction of the carbonic acid is continued until there is no more absorption he follows. If the reaction mixture becomes too mushy, a sufficient amount must be used hot alcohol must be added so that there are no excretions that could be exposed to the action would withdraw from the gaseous carbon dioxide.

The reaction mixture obtained in this way is first extracted from the insoluble decomposition products separated. Then the moderately concentrated aqueous Solution with dilute mineral acid for the purpose of breaking down the double salt and separating it the free resin acid is added, suction filtered and washed with water. The GE-

Purified mixture of acid and resinotannol is heated with the calculated amount of alcoholic potassium hydroxide (26 g KOH 10% to 1000 g of drug) for a short time to regress the potassium salts and then extracted with alcohol, the insoluble potassium salt of resinotannol remaining in the residue, the potassium salt of the Resin acid, however, goes into solution. It is obtained as a pure product from this solution by distilling off and drying at 105 °.

The end product C ₄₁ H ₆₁ O ₁ K ₃ forms a dark green powder that is odorless and has a sour-bitter-salty taste. It does not have a sharp melting point; If a little substance is gently heated on a platinum needle loop over a small Bunsen flame, first a sintering similar to enamel occurs, followed by expansion and softening. The compound burns with a glowing flame with strong expansion and leaves behind a little potassium carbonate, which evaporates in a hot flame.

Solubility of C ₄₁ H ₇ O _til K _3:

Is instantly very easy to clear red-brown liquid with bitter in cold water Taste soluble, from which it is completely separated out as water-insoluble light green flakes by dilute acids, which in dilute But ammonia dissolve again immediately.

solvent

Hot

Glacial acetic acid

Alcohol ... '. :. . .

ether

Benzene ■ ... ..

Petroleum ether

Vinegar ether

toluene

chloroform

Carbon disulfide

acetone

Caustic soda

Concentrated sulfuric acid Concentrated nitric acid.

well soluble (1: 5)

well soluble (1: 5)

completely insoluble

completely insoluble

completely insoluble

completely insoluble

soluble in traces

somewhat soluble (1:20)

soluble in traces
fairly soluble (1:10)

well soluble (1: 5)

red-yellow clear solution

no special effect

, very easily soluble (1: 2)
as well
as well

very sparingly soluble
as well
as well
as well
as well
as well
as well

very soluble (1: 2)

red-brown solution

clear yellow solution

Addition of H ₂ O gives brown

or milky cloudiness.

Reactions of the aqueous solution of C _1x H ₆₁ O ₁ K ₃ with metal salt solutions. ₁₀₀ lead acetate: complete precipitation of green flakes, insoluble in ENT ₃ . Tin chloride: complete precipitation of green flakes, insoluble in HNO ₃ . Silver nitrate: complete precipitation of green flakes, insoluble in ENT ₃ . Copper sulfate: complete precipitation d. green flakes, insoluble in ENT ₃ . Chlorbaryum: complete precipitation of green flakes, insoluble in HNO ₃ . 105

Zinc sulfate: complete precipitation d. green flakes, insoluble in ENT ₃ . Ferric chloride: incomplete precipitation of green flakes, insoluble in ENT ₃ . Magnesium sulfate: weak precipitation of green flakes, insoluble in ENT ₃ . Mercury chloride: no precipitation of green flakes, insoluble in HNO ₃ .

Therapeutic usability.

_{The salt C 41} H ₆₁ K ₃ O ₁ , which is easily soluble in water, shows diuretic effects and can therefore be used therapeutically as a diuretic.

It is already known that those contained in the leaves of Betula verrucosa Acid, betuloretinic acid, has a diuretic effect, and it is also known to increase solubility to add sodium carbonate to this acid to the birch leaf extract (cf.H ag he s Handbuch der Pharm. Praxis, Neue Ed., Volume I [1899], p. 482). By the action of an aqueous solution of sodium carbonate on the plant parts of the Betulaceae an extract is obtained, which the water-soluble Contains sodium salts of resin acids among other ingredients of the drug.

With this type of action of the sodium carbonate, naturally only neutralizes the carboxyl groups of the acid, but not the hydroxyl groups. Man thus only contains water-soluble salts of the resin

acids that are heavily mixed with foreign substances. The proportion of the latter is an average of 70 percent, and this is of course a very unfavorable ratio of the effective to the ineffective parts.

A purification of the end product with the ultimate goal of the pure representation of the effective Components cannot be carried out according to the known method.

According to the present process, however, the production of a pure preparation succeeds, if you first completely extract the drug with alcohol and thereby from the outset about 60 percent of the foreign matter is eliminated.

Due to the subsequent prolonged exposure to potassium hydroxide in alcoholic Solution are then neutralized both the carboxyl groups and the hydroxyl groups, and in the anhydrous obtained in this way alcoholic solution actually occurs through the introduced dry carbonic acid the above-described substitution of a hydrogen atom of the aromatic radical through a carboxyl group.

The substitution product obtained in this way can easily be transferred from the other constituents to the are separated in the manner described, and are obtained by the indicated process in water very easily soluble salts of a higher molecular resin acid. As these salts complete can be produced chemically pure, they naturally have a higher therapeutic value Value as the impure, possibly only about 30 percent effective product containing substances, which according to the information could be manufactured by Hager. The application of the new procedure means for these reasons a significant advance compared to the known older methods, because they are the isolation of a chemically pure, absolutely uniform compound Body, which has therapeutically very valuable properties. aside from that it may be pointed out that the body to be preserved according to the new method, ' As stated above, also chemically from those available according to the information in Hager Products is different.

Claims (1)

Patent Claim:. Process for the preparation of compounds of the composition C ₄₁ H ₆₇ O ₇ Me ₃ (where Me denotes alkali metal), which are readily soluble in water, from the leaves of Betula alba, consisting in extracting birch leaves with alcohol, treating the alcoholic extract with alkali hydroxide in heat , dry carbonic acid is introduced into the alcoholic-alkaline solution until it is completely saturated, the reaction mixture is mixed with water, the water-insoluble decomposition products are filtered off, and the two acids C ₄₁ H ₇₀ O ₇ and C ₃₉ H _{6S are removed from the then moderately concentrated aqueous solution by means of dilute mineral acid} O ₃ (resinotannol) separates and these acids are separated from one another by conversion into the Tn or dialkali salts with alcoholic alkali hydroxide.