Patented Sept.

12, 1950 2,521,805

UNITED STATES2,521,805.PATENT OFFICE

-PROCEss-FOR EXTRACTING ACONITINE.
Edward F. Rogers, New York, N.Y., assignor to
Merck & Co., Inc., Rahway, N.J., a corporation
of New Jersey
No Drawing. Application November 2, 1944,
Serial No. 561,519, --

1.
This invention relates to a process: for obtain The following.example illustrates a method of
ing the alkaloid aconitine. carrying out the present invention, but it is to
Aconitine is a poisonous narcotic alkaloid pres be understood that this example is given by way
ent-in root tubers and other plant parts of cer of illustration and not of limitation.
tain Species of plants of the genus Aconitum, par 5 Eacample:
'ticularly-tubers, of the Species Aconitum napellus.
It is: an acetyl-benzoylaconinehaving the for About 5 lb. of ground or powdered tubers are
mula C34H47NO11, and in the pure state is a white stirred for approximately 1% hours at a temper
crystalline solid, m. p. 202.3° C. It is soluble in ature of 50-55° C. with a solution of 22.7 grams
alcohol ether, and chloroform but almost insol-10 of tartaric acid in 6 liters of water (i. e., about
uble in: water. and petroleum ether, -0.37% tartaric acid solution). The mixture is
Acolaitine issuseful in the treatment of certain filtered, the residue is reprocessed with about 5
'feyers and is important as a remedy for neuralgia, liters of water containing approximately 25g of
particularly of the 5th Cranial nerve. tartaric, acid (i.e., about 0.5% tartaric acid solu
According to known methods for preparing. 15tion); filtered; and the combined filtrates are
a Conitine ground roots or tubers of Aconitum, stirred with about 1200-cc.ether: Incorder to
Tapelius have been extracted with an organic avoid emulsion formation stirring is done in such
Solvent Such as ethanol, alone or in combination a manner that no vortex is created. After strati
with Small amounts of tartaric acid or calcium fication of the aqueous and ether layers, the lay
carbonate. These processes are objectionable, 20 ers are separated and the aqueous layer is neu
however, because of the large volume of alcohol tralized using 200 g. of Sodium bicarbonate (with
needed for the extraction and further because care to minimize foaming) and then saturated
alcohol also extracts considerable amounts of un with 1% lb. of sodium chloride. The weakly alka
desired resinous and fatty material that must be line Solution thus obtained is extracted with 1000
removed before the aconitine can be concentrated 25 cc. of ether, followed by three further extractions
and purified. with 500 cc. of ether each. During each ether
It is now discovered according to the process extraction the liquids are stirred about A hour
Of the present invention that although aconitine avoiding formation of a vortex. The mixtures
has low Solubility in Water, it surprisingly is pos readily stratify and the ether layers are removed
Sible and highly practicable to extract a conitine 30 and combined.
from ground plant parts with an aqueous solvent. The combined ether extracts are washed suc
This procedure serves not only to reduce the cost cessively with three 100 cc. portions of water,
Of the extraction process by eliminating need for then stirred for A2 hour with 30 g. of anhydrous
more costly organic solvent, but also serves to sodium sulfate and filtered. The filtrate, a sub
simplify the concentration and purification of stantially colorless ether solution, is concen
the aconitine because very little resinous or fatty trated to a volume of 75 to 100 cc., then carefully
material is extracted by the aqueous solvent. diluted with twice its volume of petroleum ether
Regarded in certain of its broader aspects the (b. p. 30-60 C.) and permitted to stand at 5°
novel process, according to this invention, com C. for about 2 hours, during which time crystals
prises directly extracting ground parts of plants 40 are deposited.
of the genlls AcOnitum with a queous solvent to The clear Supernatant liquid is decanted from
obtain a crude aqueous extract, extracting the the crystalline material which then is dissolved
aqueous extract with ether, separating and Sub in Warm ethanol and cooled at 5° C. for 16 hours.
stantially neutralizing the aqueous layer thus Crystals that are deposited are removed, washed
formed, Saturating the neutralized aqueous layer 45 with cold ethanol and dried. The product so ob
with salt, extracting with ether, and obtaining tained melts at about 201-202° C.
aconitine from the extract, for example, by drying In the process as above described it is to be
the combined ether extracts, concentrating the understood that other water soluble and sub
ether solution to small volume, crystallizing stantially neutral salts can be substituted for
aconitine by addition of petroleum ether, and 50 Sodium chloride in Saturating the aqueous layer
purifying the crystalline product by recrystalliz prior to ether extraction. Likewise other sub
ing from absolute ethanol. The extracting sol stantially neutral drying agents can be substi
went employed can be water or a mildly alkaline tuted for the anhydrous sodium sulfate employed
or mildly acidic aqueous solution, water being in drying the resulting ether extract.
preferred. 55 Modifications may be made in carrying out the
 2,521,805
3 4.
present invention without departing from the genus Aconitun. With acidified water, having an
spirit and scope thereof and the invention is to acid strength equivalent to about 0.37 to 0.5%
be limited only by the appended claims. tartaric acid, to produce a crude aqueous extract,
What is claimed is: extracting the aqueous extract With ether, strati
1. The process for obtaining aconitine that 5 fying and separating the aqueous layer, neutral
comprises extracting ground parts of plants of izing the aqueous layer, and recovering aconitine
the genus Aconitum with an aqueous solvent Se from the neutralized aqueous layer. ,
lected from the group consisting of water and 5. The process for obtaining aconitine that
mildly acidic Water to produce a crude aqueOUS comprises extracting ground parts of plants of
extract, extracting the aqueous extract with 10 the genus Aconitum with water acidified with
ether, stratifying and separating the aqeous about 0.37 to 0.5% of tartaric acid to produce a,
layer, neutralizing the aqueous layer, and recover crude acqueous extract, extracting the aqueous
ering aconitine from the neutralized aqueous extract with ether, stratifying and separating the
layer. aqueous layer, neutralizing the aqueous layer, and
2. The process for obtaining aconitine that 5 recovering aconitine from the neutralized aqueous
comprises extracting ground parts of plants of layer.
the genus Acornitum with an aqueous solvent Se EDWARD F. ROGERS.
lected from the group consisting of water and REFERENCES C TED
acidified water, having an acid strength equiva
lent, to about 0.37 to 0.5%tartaric acid, to pro 20. The following references are of record in the
duce a crude aqueous extract, extracting the file of this patent: . . -
aqueous extract with ether, stratifying and sep UNITED STATES PATENTS
arating the aqueous layer, neutralizing the aque Number Name Date
ous layer, and recovering aconitine from the neu
tralized aqueous layer. . 25 1416,205 Huff ------------- May 16, 1922
3. The process for obtaining aconitine that ... , 1,447,400
1,435,187 Stoll -------------- Nov. 14, 1922
Stoll -------------- Mar. 6, 1923
comprises extracting ground parts of plants of
. . the genus, Aconitum with mildly acidic water to
produce a crude aqueous extract, extracting the OTHER REFERENCES
: aqueous extract with ether, stratifying and sep 30 Henry, Plant Alkaloids (1913), p. 340-342.
arating the aqueous layer, neutralizing the aque Henry, Plant Alkaloids (1913), p. 344. . . .
sous layer, and recovering aconitine from the neu Barrowcliff et al., “Organic Medicinal Chemi
tralized aqueous layer. cals' (Wan Nostrand Co., New York, 1920), page
87. . . . . . .
... . 4. The process for obtaining aconitine that
comprises extracting ground parts of plants of the 35