IMPROVEMENTS IN THE MANUFACTURE OF QUININE AND OTHER ALKALOIDS
Year: 1853

page_text: LETTERS PATENT to John Hall Brock Thwaites, of Bristol, Dentist,"
and William Bird Herapath, also of Bristol, M.D., for the Inven-
T
Scaled the 13th January 1854, and dated the 15th November 1853.
PROVISIONAL SPECIFICATION left by the said John Hall Brock
Thwaites and William Bird Herapath at the Office of the Com-
missioners of Patents, with their Petition, on the 15th November
1853.
We, JOHN HALL BROCK THWAITES, of Bristol, Dentist, and WILLIAM
BIRD HERAPATH, also of Bristol, M.D., do hereby declare the nature of
the Invention for "IMPROVEMENTS IN THE MANUFACTURE OF QUININE AND
OTHER ALKALOIDS " to be as follows:-
This Invention consists in first extracting the alkaloid from the bark
or other substance containing the same by means of dilute acid, then
precipitating the alkaloid by an alkali, and afterwards separating the
alkaloid from the water in which it is held in suspension or solution by
means of fusil oil, camphine, turpentine, or other hydro-carbon insoluble
in water.

page_text: SPECIFICATION in pursuance of the conditions of the Letters Patent,
filed by the said John Hall Brock Thwaites and William Bird
Herapath in the Great Seal Patent Office on the 15th May 1854.
TO ALL TO WHOM THESE PRESENTS SHALL COME, we,
JOHN HALL BROCK THWAITES, of Bristol, Dentist, and WILLIAM BIRD
HERAPATII, also of Bristol, M.D., send greeting.
WHEREAS Her most Excellent Majesty Queen Victoria, by Her
Letters Patent, bearing date the Fifteenth day of November, in the
year of our Lord One thousand eight hundred and fifty-three, in the
seventeenth year of Her reign, did, for Herself, Her heirs and suc-
cessors, give and grant unto us, the said John Hall Brock Thwaites
and William Bird Herapath, Her special licence that we, the said
John Hall Brock Thwaites and William Bird Herapath, our executors,.
administrators, and assigns, or such others as we, the said John Hall
Brock Thwaites and William Bird Herapath, our executors, adminis-
trators, and assigns, should at any time agree with, and no others, from
time to time and at all times thereafter during the term therein
expressed, should and lawfully might make, use, exercise, and vend,
within the United Kingdom of Great Britain and Ireland, the Channel
Islands, and Isle of Man, an Invention for "IMPROVEMENTS IN THE
MANUFACTURE OF QUININE AND OTHER ALKALOIDS," upon the condition
(amongst others) that we, the said John Hall Brock Thwaites and
William Bird Herapath, by an instrument in writing under our
hands and seals, or under the hand and seal of one of us, should
particularly describe and ascertain the nature of the said Invention,
and in what manner the same was to be performed, and cause the same
to be filed in the Great Seal Patent Office within six calendar months
next and immediately after the date of the said Letters Patent.
NOW KNOW YE, that we, the said John Hall Brock Thwaites
nd William Bird Herapath, do hereby declare the nature of the said
Invention, and in what manner the same is to be performed, to be
particularly described and ascertained in and by the following state-
ment thereof, that is to say:
This Invention consists in first extracting the alkaloid from the bark

page_text: or other substance containing the same by means of dilute acid, then
precipitating the alkaloid by an alkali, and afterwards separating the
alkaloid from the water in which it is held in suspension or solution by
means of fusil oil, camphine, turpentine or other hydrocarbon, insoluble
in water.
And in order that our said Invention may be most fully understood
and readily carried into effect, we will proceed to describe the process
pursued by us.
The following is the process which we employ for the extraction of
quinine and the other cinchona alkaloids:-The coarsely powdered
peruvian or other suitable bark should be boiled during one hour
or more in a solution of carbonate of soda or potassa, in propor
tion of twenty-eight pounds of carbonate to each hundred weight
of bark used, and dissolved in fifty-six gallons of water, which
process removes most of the useless gum colouring matter, acids,
and other extractive matters, and renders it more fit to be operated
upon according to our process. After boiling, the bark is to be pressed
and then thrown into a vat or tub and well agitated with cold water to
assist in removing the colouring matter and other soluble impurities;
and these operations should be repeated until all the extractive matters
are removed. The bark is now collected on a strainer and expressed
dry. The bark is then digested at a gentle heat, say 160° for one hour
or more in a mixture of hydrochloric acid and water, in the proportion
of two fluid pints of acid to fifty gallons of water for every hundred
weight of bark employed, and kept well agitated. After boiling during
one quarter of an hour, the acid liquid is run off' and strained, and the
bark again, and a third time or oftener, treated in a similar manner by
digesting and boiling in hydrochloric acid and water. These weaker
acid solutions resulting from the second and third boilings are to be
used for exhausting fresh portions of bark. The strong acid solutions
are now very gently heated with cream of lime in excess, by which the
quinine, quinidin, and cinchonine are thrown out of solution and the
liquid is allowed to cool. To this mixture is then added fusil oil, turpen-
tine, campbine, or other hydrocarbon insoluble in water and lighter than
5 it, but by preference we employ fusil oil, and in the proportion of about

page_text: one pint to each gallon of the acid solution; and the solution of the
alkaloid is assisted by well agitating the mixture. By this process the
alkaloids (or some of them only, according to the solvent employed,) are
dissolved, and on repose, the solution will be found swimming on the
top of the heavier watery fluid containing the chloride of calcium. The
lighter fluid having been drawn off by à syphon is now treated by
agitation with sulphuric acid and water in suitable proportions, (we
prefer six ounces by measure of acid to every hundred weight of bark
employed and diluted with fourteen gallons of water,) and again
repeatedly and thoroughly agitated. By this process the alkaloids are
transferred from the original solvent to the diluted sulphuric acid; and
if the agitating operation has been properly accomplished, the whole of
the quinine and other alkaloids dissolved will be found in the acid
solution. The two fluids separate on repose in consequence of the
great difference in their specific gravities, and should be separately run
off by syphons. The solvent having rendered up the alkaloids to the
acid may be again used as a solvent for fresh portions of the alkaloids.
The acid liquid containing the alkaloids in solution is now a concen-
trated mixed solution of the sulphate of quinidin, and quinine, and cin-
chonine, with a slight excess of sulphuric acid and some colouring
matter. "
It is now to be submitted to the decolorizing process, and for this
purpose it should be boiled with purified animal or vegetable charcoal,
and then filtered or strained, taking the usual precautions to avoid loss.
This solution should now be divided into two portions equal in quantity.
Into one of these a solution of caustic soda or of ammonia or of their
carbonates should be mixed in sufficient quantity to precipitate the
alkaloids contained therein without being employed in excess. This is
then to be further mixed with the other portion or half, and boiled
during one hour, if necessary. If any grey alkaloid remains undis-
solved, diluted sulphuric acid should be added cautiously, drop by drop.
If crystals form during the boiling add more water to dissolve them.
This operation properly conducted produces on cooling an abundant
proportion of crystallized disulphate of quinine mixed with some disul-
phate of quinidin, which should be collected by carefully straining.

page_text: The mother liquids still contain some disulphate of quinine, more disul-
phate of quinidin, and usually sulphate of cinchonine. Upon concen-
trating the solution by evaporation and then allowing it to cool, a large
proportion of the two former substances may be recovered, and still
more by a second and third repetition of the process of evaporation and
crystallization.
.
The product of all these crystallizations being mixtures of the disul-
phates of the cinchona alkaloids, quinine, quinidin, with some cinchonine,
should be purified by recrystallization or other process in the usual
manner, so as to fit it for market, and render it a saleable article, and
dried with all ordinary and proper precautions to avoid injury. The
quinine, quinidin, and cinchonine remaining in the mother liquids
should be extracted by precipitation with a solution of caustic soda,
ammonia, potassa, or other suitable precipitant, and then agitated
with fusil oil, turpentine, camphine, or other solvent, as before de-
scribed.
The dark brown red alkaline fluid obtained by the preparatory pro-
cess of boiling with an alkali is now to be mixed with the liquid (con-
taining chloride of calcium,) from which the alkaloids have been
obtained by agitating with a solvent, and the deeply colored precipi-
tated carbonate and other salts of lime and other impurities are allowed
to subside, and should the liquid be still alkaline or contain excess of
carbonate of soda, a solution of chloride of calcium should be added to
precipitate the carbonic acid as carbonate of lime, which must be sepa-
rated. The liquid separated (still containing chloride of sodium, the
hydrochlorates of quinine, and other cinchona alkaloids,) is to be con-
centrated by evaporation, if necessary, and then heated with slaked
lime or cream of lime, and the precipitated alkaloid removed by the
addition of fusil oil, turpentine, or other solvent, and the alkaloids are
separated as before described. We have thus described minutely the
manner of preparing the cinchona alkaloids, and we would here remark
that in the foregoing description the quantities specified are suitable for
operating on an average specimen of bark; but should the quantity of
alkaloids in the bark to be treated vary considerably from the average,
the quantities of the re-agents employed should be varied in proportion.

page_text: And we would further remark that this process is also applicable to
other alkaloids of which the salts crystallize with facility, and which are
insoluble or nearly so in water, only in each case the solvent most ap-
plicable to the alkaloid in question should be selected from the class
above mentioned. But as other alkaloids which are insoluble or nearly
so in water form salts which crystallize only with difficulty, we will
proceed to describe the modifications which we introduce into the pro-
cess for the preparation of this class of alkaloids, and in order to do so
we will proceed to describe as examples the manner in which we ex-
tract veratria and sabadillia.
The coarsely ground root stalk of the veratrium album being used
should be treated precisely in the manner described for treating peruvian
or other bark, varying the quantities, however, according to the altered
circumstances of the case, and the quantity of alkaloid contained in the
matters under treatment, until that part of the process is arrived at
where the acid solution which has been boiled with animal or vegetable
charcoal is (according to the directions) to be divided into two parts,
when in place of doing so we exactly neutralize it by carbonate of
potassa, or of soda, and concentrate it by evaporation, if necessary, to a
convenient bulk when cooled below 122°; or even when quite cold the
alkaloids are to be. precipitated by a solution of soda or potassa, and
the product carefully collected on a strainer. The mixed and impure
alkaloids should be washed or edulcorated with cold water in the ordi-
nary manner to remove all soluble impurities. The mixture of alkaloids
should now be boiled in a sufficient quantity of water to remove all the
soluble sabadillia and resin of veratria, the former of which separates on
the cooling of the liquid in a crystalline form, and may be further
purified by a second crystallization, if necessary, for the purpose re-
quired. The residuary alkaloid insoluble in boiling water consists of
veratria mixed with a gum resin, and may be further purified by the
action of alcohol and ether, as is well understood, if it be thought
necessary to do so, but the product will be sufficiently pure for all
ordinary purposes.
Having thus described the nature of our Invention, and the manner
of performing the same, we would have it understood that we do not

page_text: confine myself to the exact details described, but what we claim is,
the use of fusil oil, camphine, turpentine, or other hydrocarbon insoluble
in water, in the manner described for separating alkaloids from the
liquid in which they are held in suspension or solution.
In witness whereof, we, the said John Hall Brock Thwaites and
William Bird Herapath, have hereunto set our hands and seals,
this Twelfth day of May, in the year of our Lord One thousand
eight hundred and fifty-four.
Witness,
JOSEPH GRIFFITHS SWAYNE, M.D.,
of Clifton.
WILLIAM CHARLES,
32 Old Market Street, Bristol.