Process for the Production of Albumen Substances and their Derivatives Abundantly Substituted with Halogen.
Year: 1898

page_text: Process for the Production of Albumen Substances and their
Derivatives Abundantly Substituted with Halogen.
I, ALEXANDER MELVILLE CLARK, of the Firm of A. M. & Wm. Clark, of 53,
Chancery Lane, in the County of Middlesex, Fellow of the Chartered Institute of
Patent Agents, do hereby declare the nature of this invention (a communication
to me by Ludwig Wilhelm Gans, trading as the Pharmaceutisches Institut; of
41, Hochstrasse, Frankfort-on-the-Main, Germany) to be as follows:-
If albumen-substances or their derivatives be halogenized (with iodine, bromiue,
or chlorine) there is at once produced an abundant quantity of hydrogen halide
(HI, HBr, HCI) which partly combines with the molecule of albumen and partly
remains free in the solution. These not inconsiderable quantities of hydrogen
halide now act on the one hand with a decomposing action upon the albumen
substances, especially when the operation takes place in heat-which is necessary
in the case of bromine and iodine--whilst on the other hand they prevent a copious
substitution of the albumen molecule with halogen. But halogen-albumen
preparations have a greater value, the more halogen they contain in combination
with the molecule, and the less they are decomposed. In order to obviate both of
these drawbacks and in order to obtain preparations which are not altered by
hydrogen halide, and which are also abundantly substituted with halogen, there are
several ways all of which effect the destruction of the hydrogen halide produced.
Either the operation is conducted in a solution which is carefully continually
kept neutralized which may be effected by adding corresponding alkali to the
hydrogen halide produced and then further halogenizing. Bi-carbonate of soda is
especially suitable for neutralizing when iodizing, because it certainly neutralizes
the powerful hydrogen halide acids but does not combine the iodine like the alkalies
so that an excess does not cause any harm.
Or halogenization is effected by decomposing the hydrogen halides or their salts by
means of a galvanic current. In this manner halogen is produced in the nascent
state, which acts at once upon surrounding albumen. The hydrogen halide
produced in this reaction is decomposed anew by the electric current so that it
In this manner
cannot exert any injurious action upon the albumen molecule.
fluorine may also be caused to act upon albumen and thus products are obtained
which contain fluorine firmly combined in the molecule.
It is obvious that by the above described two methods all the albumen substances
(albumens, albumoses, peptones, albumenoids, etc., as also their derivatives, so far
as they still bear an albuminous character-such as divisional products which give
the reactions of albumen (biuret reactions, Millon's reactions, etc., etc.)-can be
halogenized. Contrary to the halogen-albumen products that are obtained without
neutralizing the hydrogen halide whether halogen is allowed to act until complete
saturation or not-the preparations produced hereby represent not only derivatives
which are not split by acid, but they also contain a multiple of substituted
halogen.

page_text: For example, by allowing iodine to act upon casein or casein-alkali the mixture
is at once acid. But iodine-casein which has been produced by adding iodine until
there is a quantity of permanently free iodine in the mixture, contains scarcely one
per cent. of iodine combined in the molecule; the greater part of the iodine is in a
state of admixture either mechanically or in the form of hydrogen iodide. But if
now the hydrogen iodide be neutralized, then a further absorption of iodine takes
place which is indicated not only by the disappearance of the added iodine but
also by the "rising" of the iodine which has entered (being substituted) in the
albumen molecule. If alkali is not allowed to flow into the mixture continuously,
but iodine is added each time until saturation, and the mixture be then neutralized,
then it must be neutralized six times at least until no more iodine is taken up.
The non-split product finally produced contains six to seven per cent of iodine in
substitution in the albumen molecule and if it be split with alkali a divisional
product is obtained containing fifteen to sixteen per cent. of iodine, whereas in the
known bodies of this class far less iodine was substituted because the process
began with less abundantly substituted iodine-albumen substance.
In iodizing, the preferable procedure is to mix a solution of albumen with
bi-carbonate of soda, and iodine, or in iodizing to allow soda lye to flow in slowly
whilst constantly testing with litmus paper. If then the mixture does not take up
any more iodine permanently, it can now be precipitated with acid (preferably
acetic acid because it does not decompose the Na I produced); and then washed
cold and hot in water and alcohol and dried. Or the soda salt of the respective
albumen is precipitated by means of acetone or alcohol, whereby the excess of
iodine and iodide of soda is at the same time removed.
The various albumen substances which are substituted with iodine in this
abundant manner, contain considerably higher amounts of iodine than could be
otherwise obtained. The non-split casein contains up to about seven per cent. of
iodine. The non-split egg-albumen contains up to about six per cent. of iodine, and
peptone contains up to about two per cent. of iodine.
The iodine-albumen-substances still shew for the greater part the biuret reaction,
whilst Millon's reaction is destroyed by the entrance of iodine. The albumen
which has been split by acids or alkalis, so far as it still shews the characteristics of
albumen biuret reactions, Millon's reactions &c., contains, by the copious substitution
with iodine, up to thirteen to sixteen per cent. of iodine. The iodizing operation is
effected preferably in heat (80° to 90° C.).
The bromizing results are quite analogous. In this case also, the substances
must be neutralized several times and bromine must be allowed to act further
in order to produce higher substitution values of bromine and to obviate
splitting. The bromizing operation is successful to a sufficient degree at about
50° C. The amounts of bromine consumed amount in the case referred to, to
about 50% of the weight of the egg-albumen. Of this considerably over 40 is
converted into HBr by oxidation of the albumen molecule and only a small portion
enters into the molecule.
The production of chlorine-albumen may be effected in the cold. Otherwise it
is analogous to the process for the production of the products of bromine and
iodine. Only in this case neutralization must be effected with double care, because
strong hydrochloric acid (HCI) not only produces decompositions, but also by
reason of considerable precipitates would otherwise remove by simple mechanical
action, a portion of the albumen from the copious chlorination.
The chlorine derivatives of the non-split albumen substances contain up to about
two per cent. of chlorine. If they are split, products containing four and more
per cent. of chlorine are produced. The production of halogen-albumen substances
by electro-chemical process takes place as follows:-For example, fluorine albumen
is obtained by adding fluoride of ammonium to a solution of albumen and then
passing a current through it. 100 grammes of egg-albumen dissolved in one litre
of water are mixed with 20 grammes of fluoride of ammonium and then a current
of a strength of ten ampères is passed through the mixture. The electrodes may

page_text: be 3 by 5 centimetres in dimension. The internal resistance is very great so that
the active current is only two ampères. The battery is disconnected after 24
hours. The product thus obtained is an undecomposed fluorine albumen which after
purification contains up to about one per cent. of fluorine firmly combined in the
In the same manner other albumen substances can be substituted
albumen molecule.
with fluorine.
For the purpose of chlorinating, bromizing, and iodizing by electro-chemical
process with the object of producing highly substituted albumen derivatives that
are not further altered, the procedure is exactly the same as in the case of fluorine
and if only sufficient halogen has been present there is produced according to the
duration of the action of the current a halogen substitution product of albumen which
considerably exceeds, as regards its percentage of organic halogen, the albumen
which has been halogenized up to simple saturation.
These products are employed for medicinal purposes in the same manner as
other halogen albumen substances and they have a more energetic action.
Dotad this 23rd day of March 1898
A. M. & WM. CLARK,
Chartered Patent Agents, 53, Chancery Lane, London.
Process for the Production of Albumen Substances and their
Derivatives Abundantly Substituted with Halogen.
I, ALEXANDER MELVILLE CLARK, of the Firm of A. M. & Wm. Clark, of 53,
Chaucery Lane, in the County of Middlesex, Fellow of the Chartered Institute of
Patent Agents, do hereby declare the nature of this invention (a communication
to me by Ludwig Wilhelm Gans, trading as The Pharmaceutisches Institut, of 41,
Hochstrasse, Frankfort-on-the-Main, Germany), and in what manner the same is to
be performed, to be particularly described and ascertained in and by the following
statement :-
If albumen-substances or their derivatives be halogenized (with iodine, bromine,
or chlorine) there is at once produced an abundant quantity of hydrogen halide
(HI, HBr, HCI) which partly combines with the molecule of albumen and partly
remains free in the solution. These not inconsiderable quantities of hydrogen halide
now act on the one hand with a decomposing action upon the albumen substances,
especially when the operation takes place in heat-which is necessary in the case of
bromine and iodine-whilst on the other hand they prevent a copious substitution of
the albumen molecule with halogen. But halogen-albumen preparations have a
greater value, the more halogen they contain in combination with the molecule and
the less they are decomposed. In order to obviate both of these drawbacks, and in
order to obtain preparations which are not altered by hydrogen halide, and which
are also abundantly substituted with halogen, there are several ways all of which
effect the destruction of the hydrogen halide produced.
Either the operation is conducted in a solution which is carefully kept continually
neutralized which may be effected by adding corresponding alkali to the hydrogen
halide produced and then further halogenizing. Bi-carbonate of soda is especially
suitable for neutralizing when iodizing, because it certainly neutralizes the powerful
hydrogen halide acids but does not combine the iodine like the alkalies so that an
excess does not cause any harm.
Or halogenization is effected by decomposing the hydrogen halides or their salts
by means of a galvanic current. In this manner halogen is produced in the nascent
state, which acts at once upon surrounding albumen. The hydrogen halide pro-

page_text: duced in this reaction is decomposed anew by the electric current so that it cannot
exert any injurious action upon the albumen molecule. In this manner fluorine may
also be caused to act upon albumeu and thus products are obtained which contain
fluorine firmly combined in the molecule.
It is obvious that by the above described two methods all the albumen substances
(albumens, albumoses, peptones, albumenoids, etc.) as also their derivatives, so far
as they still bear an albuminous character-such as divisional products which give
the reactions of albumen (biuret reactions, Millon's reactions, etc., etc.)-can be
halogenized. Contrary to the halogen-albumen products that are obtained without
neutralizing the hydrogen halide whether halogen is allowed to act until complete
saturation or not-the preparations produced hereby represent not only derivatives
which are not split by acid, but they also contain a multiple of substituted
halogen.
For example by allowing iodine to act upon casein or casein-alkali, the mixture
is at once acid. But iodine-casein which has been produced by adding iodine until
there is a quantity of permanently free iodine in the mixture, contains scarcely one
per cent. of iodine combined in the molecule; the greater part of the iodine is in a
state of admixture either mechanically or in the form of hydrogen iodide. But if
now the hydrogen iodide be neutralized, then a further absorption of iodine takes
place which is indicated not only by the disappearance of the added iodine but also
by the "rising" of the iodine which has entered (being substituted) in the albumnen
molecule. If alkali is not allowed to flow into the mixture continuously, but iodine
is added each time until saturation, and the mixture be then neutralized, then it
must be neutralized six times at least until no more iodine is taken up. The non-
split product finally produced, contains six to seven per cent. of iodine in substitu-
tion in the albumen molecule and if it be split with alkali a divisional product is
obtained, containing fifteen to sixteen per cent. of iodine, whereas in the known
bodies of this class far less iodine was substituted because the process began with
less abundantly substituted iodine-albumen substances.
In iodizing, the preferable procedure is to mix a solution of albumen with
bi-carbonate of soda, and iodine, or in iodizing to allow soda lye to flow in slowly
whilst constantly testing with litmus paper. If then the mixture does not take up
any more iodine permanently, it can now be precipitated with acid (preferably acetic
acid because it does not decompose the Nal produced); and then washed cold and
hot in water and alcohol and dried. Or the soda salt of the respective albumen is
precipitated by means of acetone or alcohol, whereby the excess of iodine and
iodide of soda is at the same time removed.
The various albumen substances which are substituted with iodine in this
abundant manner, contain considerably higher amounts of iodine than could be
otherwise obtained. The non-split casein contains up to about seven per cent. of
iodine. The non-split egg-albumen contains up to about six per cent. of iodine, and
peptone contains up to about two per cent. of iodine.
The iodine-albumen substances still shew for the greater part the biuret reaction,
whilst Millon's reaction is destroyed by the entrance of iodine. The albumen which
has been split by acids or alkalies, so far as it still shews the characteristics of
albumen (as above mentioned, vi, biuret reactions, Millon's reactions, etc.,) contains,
by the copious substitution with iodine, up to thirteen to sixteen per cent. of
iodine. The iodizing operation is preferably carried out at a temperature
of 20° to 50° C.
The bromizing results are quite analogous. In this case also, the substances
must be neutralized several times and bromine must be allowed to act further in
order to produce higher substitution values of bromine and to obviate splitting.
The bromizing operation is successful to a sufficient degree at about 50° C. The
amounts of bromine consumed amount in the case referred to, to about 50 % of the
weight of the egg-albumen. Of this considerably over 40 % is converted into HBr
by oxidation of the albumen molecule and only a small portion enters into the
molecule.

page_text: The production of chlorine-albumen may be effected in the cold but preferably at
a temperature of 20° to 50° C. Otherwise it is analogous to the process for the
production of the products of bromine and iodine. Only in this case neutralization
must be effected with double care, because strong hydrochloric acid (HG)) not
only produces decompositions, but also by reason of considerable precipitates would
otherwise remove by simple mechanical action, a portion of the albumen from the
copious chlorination.
The chlorine derivatives of the non-split albumen substances contain up to about
two per cent. of chlorine. If they are split, products containing four and more
per cent. of chlorine are produced. The production of halogen-albumen substances
by electro-chemical process takes place as follows:-For example, fluorine albumen
is obtained by adding fluoride of ammonium to a solution of albumen and then
passing a current through it. 100 grammes of egg-albumen dissolved in one litre
of water, are mixed with 20 grammes of fluoride of ammonium and then a current of
a strength of ten ampères is passed through the mixture. The electrodes may be
three by five centimetres in dimension. The internal resistance is very great so
that the active current is only two ampères. The battery is disconnected after
twenty-four hours. The product thus obtained is an undecomposed fluorine
albumen which after purification contains up to about one per cent. of fluorine firmly
combined in the albumen molecule. In the same manner other albumen substances
can be substituted with fluorine.
For the purpose of chlorinating, bromizing, and iodizing by electro-chemical
process with the object of producing highly substituted aibumen derivatives that
are not further altered, the procedure is exactly the same as in the case of fluorine
and if only sufficient halogen has been present there is produced, according to the
duration of the action of the current, a halogen substitution product of albumen
which considerably exceeds, as regards its percentage of organic halogen, the
albumen which has been halogenized up to simple saturation.
These products are employed for medicinal purposes in the same manner as other
halogen-albumen substances and they have a more energetic action.
Having now particularly described and ascertained the nature of the said
invention and in what manner the same is to be performed I declare that what
I claim is :-
The production of albumen substances (albumens, albuminates, albumoses,
peptones,) and albumen derivatives such as they can be obtained by splitting with
acids and alkalies without destroying their albuminous origin, substituted with
halogen (iodine, bromine, chlorine, fluorine,) as herein described.
Dated this 30th day of November 1898.
A. M. & WM. CLARK,
Chartered Patent Agents, 53, Chancery Lane, London.