PREPARATION OF QUININE-CARBONIC-BENZYL-ETHER
Year: 1899

page_text: -Cl
O.CH
CoHg,N,O, HỎi + CO
= CO:
.2HCl.
O.C₂H
O.CHNO
When the operation is complete, the benzene is distilled off, the residue dis-
solved in water, the quinine carbonic ethyl ether produced being precipitated by
means of alkali, and recrystallised from dilute alcohol, when a small quantity of
quinine, which has escaped the action of the chloroformic ether, remains in the
mother liquor.
Obviously the product of reaction may be removed from the benzene solution
by agitation with water, or with dilute acid. Other anhydrous quinine-salts (for
example, 373 kilograms of anhydrous quinine sulphate) may be used in the
place of quinine hydrochloride.
The quinine carbonic ethyl ether obtained in this way has the properties
described in the Specification of the aforesaid Patent.
EXAMPLE III.
PREPARATION OF QUININE-CARBONIC-BENZYL-ETHER.
36°1 kilograms of anhydrous quinine hydrochloride are suspended in 150 kilo-
grams of benzene, and treated with 171 kilograms of chloroformic benzyl ether,
added gradually to the boiling liquid. When the reaction is complete, the
benzene is distilled off, or the hydrochloride of quinine carbonic benzyl ether is
extracted from it by agitation with water, or a dilute acid. On adding an alkali
the ether is set free, and may be recrystallised from dilute alcohol.
Quinine carbonic benzyl ether crystallises in slender, white needles which melt
at 110° Centigrade and dissolve readily in alcohol, ether, benzene, and chloroform.
Dated this 18th day of November 1899.
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C.,
Agents,
Improvements in the Manufacture of Pharmaceutical Preparations of
Quinine.
I, JAMES YATE JOHNSON, of 47, Lincoln's Inn Fields, in the County of London,
Gentleman, do hereby declare the nature of this invention (which has been
communicated to me from abroad by Vereinigte Chininfabriken, Zimmer & Com-
pany, of Frankfort-on-Maine, in the German Empire) and in what manner the
same is to be performed to be particularly described and ascertained in and by
the following statement:-
In the Specification of Letters Patent No. 4991 of 1896 is described the obtain-
ing of pharmaceutical products by acting on the cinchona-bark alkaloids with
derivatives of chlorocarbonic acid, such for example as phosgene, and chloro-
carbonic ether.
Now my foreign correspondents have found that, in this process, the said
alkaloids can be replaced by their more readily obtainable salts. The method of

page_text: procedure is to act on the alkaloidal salt preferably in the anhydrous condition
with the particular derivative of chlorocarbonic acid either alone, or dissolved in
some suitable solvent.
EXAMPLE I.
3 PREPARATION OF THE CHLOROCARBONIC ETHER OF QUININE OR CHLOROCARBONYI.
QUININE.
36.05 kilograms of anhydrous quinine hydrochloride (two molecular proportions)
are dissolved in 200 kilograms of chloroform, and into the cooled solution there
is passed 9'9 kilograms of phosgene (one molecular proportion) which also can
be in excess.
The reaction proceeds according to the equation
'
C₂HNO, HCl + CO/
= CO/
\OC₂H₂
\O.CHNO
.2HCl.
When the operation is complete, the benzene is distilled off, the residue dis-
solved in water, the quinine carbonic ethyl ether produced being precipitated by
means of alkali, and recrystallised from dilute alcohol when a small quantity of
quinine, which has escaped the action of the chloroformic ether, remains in the
mother liquor.
Obviously the product of reaction may be removed from the benzene solution
by agitation with water, or with dilute acid. Other anhydrous quinine salts (for
example 37.3 kilograms of anhydrous quinine sulphate) may be used in the
place of quinine hydrochloride.
The quinine carbonic ethyl ether obtained in this way has the properties
described in the Specification of the aforesaid Patent.
EXAMPLE III.
PREPARATION OF QUININE CARBONIC BENZYL ETHER.
361 kilograms of anhydrous quinine hydrochloride are suspended in 150 kilo-
grams of benzene, and treated with 17'1 kilograms of chloroformic benzyl ether,
added gradually to the boiling liquid. When the reaction is complete, the
benzene is distilled off, or the hydrochloride of quinine carbonic benzyl ether is
extracted from it by agitation with water, or a dilute acid. On adding an alkali
the ether is set free, and may be recrystallised from dilute alcohol,

page_text: Quinine carbonic benzyl ether crystallises in slender, white needles which melt
at 110° Centigrade and dissolve readily in alcohol, ether, benzene, and chloroform.
Having now particularly described and ascertained the nature of this inven-
tion and in what manner the same is to be performed I declare that what I
claim is:-
1. The manufacture of pharmaceutical preparations of quinine by acting on a
quinine salt with a derivative of chlorocarbonic acid substantially as hereinbefore
explained.
2. The manufacture of pharmaceutical preparations of quinine as herein before
described under the several examples.
Dated th: 1941 1
1000
JOHNSONS & WILLCOX,
47, Lincoln's Inn Fields, London, W.C.,
Agents.