Improvements in Obtaining Sulphonic Acids and Sulphone-like Compounds, Free from Inorganic Salts, from the Neutralised Product of the Action of Sulphuric Acid upon Mineral and similar Oils, and particularly Hydro-carbons Artificially or Naturally Sulphuretted.
Year: 1893

page_text: Date of Application, 21st Mar., 1893
Complete Specification Left, 21st Dec., 1893-Accepted, 21st Mar., 1894
PROVISIONAL SPECIFICATION.
Improvements in Obtaining Sulphonic Acids and Sulphone-like
Compounds, Free from Inorganic Salts, from the Neutralised
Product of the Action of Sulphuric Acid upon Mineral and
similar Oils, and particularly Hydro-carbons Artificially or
Naturally Sulphuretted.
I, Dr. LUDWIG OTTO HELMERS of No. 21 Bohnenstrasse Hamburg in the
Empire of Germany, Chemist, do hereby declare the nature of this invention to be
as follows:-
For separating the sulphonized compounds produced by the action of sulphuric
acid on mineral or similar oils particularly on hydro-carbons artificially or naturally
sulphuretted and lately frequently employed in therapeutics, from the still adhering
sulphuric acid or their salts two methods have been essentially hitherto employed.
Either the reaction produced has been dissolved in water and then separated again
by adding salts or acids (ride British Patent No. 10523 of July 24th 1884) or it
has been subjected to the dialysis. But both methods offer great inconveniences.
According to the first method always considerable quantities of the salt used for
salting out remain in the sulphonized product, while according to the second very
tedious method there diffuse, besides the inorganic acids or salts respectively, also
considerable quantities of sulphonic acids (or the salts of the same). But it results
thereby not only a considerable loss of a therapeutically highly important
constituent, but also the non-diffused portion of the sulphonized product loses,
owing to the want of the organic salts considerably of its readiness of solubility
in water. These inconveniences of the hitherto used methods are obviated by
a process which is accomplished by treating with several solvents the sulphonizing
products neutralized by an alkali. In trying to find out such solvents it is however
ascertained, that, except water, there is no liquid dissolving this kind of sulphonized
products in an easy and complete manner. From the aqueous solutions of the same
especially after the addition of a salt, such as chloride of sodium or carbonate
of ammonium-benzene, ether, chloroform and the like extract apparently all the
organic matters, since the aqueous layer appearing nearly colourless; but there
remain still, besides the saturating salts, organic constituents in solution in the
water. But the want of these substances has for its effect that the product obtained
after distilling off the chloroform etc., has lost in part, like the product obtained by
dialysis, its solubility in water. In treating however the sulphonized products
neutralized by an alkali after they have been freed as much as possible from water,
with a mixture of alcohol and chloroform or of alcohol and benzene and the like, it
is possible to dissolve all the organic bodies and to separate them by this means
from the inorganic salts remaining insoluble. If it is desired to separate simul-
taneously in eliminating the inorganic salts, also the acid compounds from the
neutral ones, the extraction by alcohol and the other solvent must take place
successively. In the alcoholic extract are then dissolved the sulphonic acid salts,
in the chloroform, benzene etc. extract the sulphone like bodies, where it is indifferent
in which order the extracting means are employed. In many cases the alcohol
extract alone suffices for effecting the separation. For as the organic constituents
of the residue remaining after the extraction by alcohol have become insoluble in
water owing to the removal of the sulphonic acid, salts, the saturating salts may be
eliminated from the residue by washing out with water. This latter method of
separation is particularly advantageously employed when the application of easily
inflammable liquids or of liquids noxious to health is to be avoided.

page_text: If there is the question of compounds of sulphonic acids with such bases, the
sulphates of which are soluble in alcohol, such as sulphate of lithium, the soluble
sulphate must be eliminated prior to the extraction with the aid of alcohol by
salting and the neutralized reaction product with the aid of chloride of sodium,
sulphate of ammonium or the like.
If applied for instance to the "ichthyol" the process is carried out in the
following manner.
After the reaction product of sulphuric acid on the Seefeld mineral oil has
been separated as much as possible from the sulphuric acid in excess by
deposition or by salting out and by extraction with the aid of petroleum-ether
from the non-sulphonized hydro-carbons, it is neutralized by means of soda, potash,
ammonia or the like, then it is evaporated and repeatedly extracted by a strongest
possible alcohol, whilst the extraction may be aided by heating. It is however not
possible to exhaust completely the product by alcohol, as also the neutral sulphone like
compounds are not entirely insoluble in alcohol. A complete extraction is however
not necessary and even not desirable, as the sulphonic acid salts easily dissolve in
alcohol and would merely be contaminated, in the case of a longer extraction by
sulphones.
In practice for the most part the double quantity of alcohol referred to the
weight of the "ichthyol" employed, is sufficient. The organic constituents of the
residue remaining after the extraction by alcohol are then already entirely insoluble
in water and the saturating salts may therefore be separated from the same by
washing out with water. In place of this somewhat tedious process the residue
may also be extracted by benzene, chloroform, and the like. The neutral sulphone
like compounds are thereby dissolved, while the inorganic salts remain in a non-
dissolved condition. For producing the sulphonic acid salts in a pure state the
alcohol is distilled off from the alcoholic solution. The remaining brown body
contains still small quantities of the sulphone like compounds which are
removed by extraction with the aid of benzene and the like. In a completely
dry state the pulverable salts form a highly hygroscopic mass of bitter Havour
and weak smell.
The second product, the neutral sulphone like compounds, form a greenish-black
inodorous mass which may easily be converted into a fine powder. The substance
is easily soluble in chloroform and benzene with more difficulty in ether and nearly
insoluble in alcohol. In pure water it does not dissolve, but the presence of the
first product, the sulphonic acid alkali salts, especially when heated, renders it
soluble. The proportion of the quantity of the sulphonic acid compounds to that
of the sulphone like compounds depends upon the mode of manufacturing. So, for
instance, a high temperature reduces in the action of the sulphuric acid on the
Seefeld oils the out-put of acid substances, and in consequence thereof the portion
which is soluble in alcohol and determinates the solubility in water of the whole
reaction product.
Dated this 14 1
1000

page_text: CUDIT LIVIE DI DUIFICATION.
Improvements in Obtaining Sulphonic Acids and Sulphone-like
Compounds, Free from Inorganic Salts, from the Neutralised
Product of the Action of Sulphuric Acid upon Mineral and
similar Oils, and particularly Hydro-carbons Artificially or
Naturally Sulphuretted.
1, Dr. LUDWIG OTTO HELMERS of No. 21 Bobnenstrasse Hamburg in the
Empire of Germany, Chemist, do hereby declare the nature of this invention, and
in what manner the same is to be performed, to be particularly described and
ascertained in and by the following statement :-
My invention has relation to the production and more particularly to the
purification of sulphonized compounds consisting of sulphonic acid salts and
sulphones or sulphone-like bodies, now recognized as valuable therapeutic agents,
and to the separation of the sulphonic acid salts from said sulphones and
sulphone-like bodies.
The purification of these sulphonized bodies consists essentially in the elimination
therefrom of the sulphuric acid employed in their production from mineral or
similar oils and particularly from hydro-carbons naturally or artificially sulphuretted,
or in the elimination therefrom of the salts of said acid when the sulphonized
product has been neutralized by means of an alkali which purification has heretofore
been effected in two ways, to wit: First by dissolving the sulphonized product in
water and then separating the same by means of a salt, as described in the
Specification of Letters Patent No. 10523 cf July 24th 1884 and second, by
dialysis.
Both these methods present difficulties and disadvantages. In the purification
according to the first method referred to all of the salt used in the salting out
cannot be removed leaving the final product in a more or less impure state
while according to the second method the inorganic salt is not only diffused,
but a certain proportion of the sulphonic acids or their salts also diffused
entailing considerable loss of this valuable therapeutic agent, which loss also
reduces the solubility in water of the final product, owing to the fact that the
sulphones or sulphone-like bodies are per se insoluble in water, and become
soluble only in the presence of sulphonic acids or their salts, so that the degree
of solubility in water of the sulphonized compound will depend upon the proportion
of sulphonic acids present.
With the exception of water there is so far as I know no solvent that will
completely dissolve these sulphonized compounds, there are solvents, however,
that will readily dissolve individual constituents of the said compounds, then, for
instance, alcohol will readily dissolve the sulphonic acid salts, while chloroform,
benzine, and other like bodies will readily dissolve the sulphones and sulphone-like
bodies, and my invention lies in the use of two of these solvents, either collectively,
for the purpose of completely dissolving the sulphonized compounds, or separately
for the purpose of separating the sulphonic acid salts from the sulphones or
sulphone-like bodies.
Said solvents I may term compound solvents which are capable of dissolving all
of the organic constituents, namely, the sulphonic acid salts as well as the sulphones
or sulphone like bodies.
For instance, if an aqueous solution of a sulphonized compound, such as are
obtained by the action of sulphuric acid upon naturally or artificially sulphuretted
mineral oils, is first neutralized by means of an alkali, then freed from as much of
the water as possible, as by evaporation, and then treated with a mixture of alcohol
(ethylic or other alcohols) and chloroform, or alcohol and benzine, or alcohol 'and
ether, all of the organic constituents referred to will be dissolved out, leaving the

page_text: inorganic constituents behind, they being insoluble in said compound solvent, the
organic compound being obtained in a pure state, and may then be freed from
the solvent by distillation or evaporation.
From this purified sulphonized compound the sulphonic acid salts may be readily
separated from the neutral sulphones or sulphone like bodies or vice versa, by means
of a solvent of the sulphones or sulphone-like bodies, as chloroform, benzine, ether,
or the like, or the sulphonic acid salts may be separated by means of a solvent
thereof, as alcohol. On the other hand the separation into sulphonic acid salts,
sulphone like bodies and the inorganic salts may be effected by alcohol (ethylic and
other alcohols) alone, in view of the fact that the sulphones and sulphone like
bodies become insoluble in water after the separation thereform of the acid
constituents (sulphonic acid salts) and as the inorganic salts remain soluble in
water the latter can readily be removed from the sulphones.
This latter process is of especial advantage because highly inflammable. liquids,
as benzine, ether, and the like, or liquids that are detrimental to health' as
chloroform are entirely avoided.
that
From what has been said above it will be understood that it is necessary
the neutralizing or saturating salt employed should be insoluble in the solvents
referred to so that only such alkalies can be used as will form with the sulphuric
acid, combinations or salts that are insoluble in said solvents, as for instance,
potash, or soda, or ammonia. Yet such sulphonic acid salts, as the lithium salt,
may be produced without necessitating the obtainment before the pure free acid-
as for instance by acidifying the cleaned sulphonic acid sodium with the aid of
hydrochloric acid-and in this case the following process may be employed.
The primary reaction mixture, that is to say, the product of the reaction
resulting from the treatment with sulphuric acid of a naturally or artificially
sulphuretted mineral oil is first neutralized by means of lithium carbonate, then
salted out repeatedly by means of a salt insoluble in alcohol, as sodium chloride,
after which the water is removed, whereby the lithium sulphate is also removed,
leaving only common salt in the sulphonized compound, which latter may be
removed from the lithium salt of the sulphonic acids as above described. Instead
of sodium chloride, ammonium sulphate or the like may be employed for the
salting out.
As an example of the mode of carrying out my invention I will describe the
same in its application to the purification of the well known sulphonized com-
pound, ichthyol, and to the separation of its sulphonic acids and sulphones or
sulphone-like constituents.
The product resulting from the reaction of sulphuric acid upon Seefeld mineral
oil after being freed from excess of acid as much as possible in a well known
manner, and after separation from the non-sulphonized hydro-carbon by means of
petroleum-ether, is neutralized with an alkali, as soda, for instance. The solution
is then evaporated and all of the organic constituents (sulphonic acid salts,
sulphones or sulphone like bodies) are dissolved out by means of a compound
solvent consisting of alcohol and of chloroform, for instance, the inorganic salt,
sodium sulphate remaining behind, since it is insoluble in said compound solvent.
The said solvent is then eliminated by evaporation or distillation from the
sulphonized constituents, which latter are thus obtained in a pure form.
If it is desired to separate the sulphonic acid salts from the sulphones and
sulphone like bodies, the compound is treated either with a solvent of the sulphones
or sulphone like bodies, such as chloroform, or with alcohol as a solvent of the
sulphonic acid salts as above set forth. This separation may, however, be effected
simultaneously with the purification of the ichthyol as follows:
The neutral anhydrous ichthyol is first treated with alcohol, the proportion of
the latter by weight being preferably about twice that of the material treated, the
alcohol used being as strong as possible; by the application of heat the process of
dissolution is accelerated. After the sulphonic acid salts have been removed by
dissolution the sulphoues and sulphone-like bodies can be separated from the

page_text: inorganic constituents by washing with water in which the former are insoluble,.
while the latter are soluble.
The brown residue remaining after treatment of the ichthyol with alcohol, still
contains small quantities of sulphone like bodies which may be extracted by further.
treatment with chloroform, benzine, or the like. The sulphuric acid alkali salts are
thus obtained in a pure condition, and when dry can be readily pulverized, they are
highly hygroscopic, have a bitter taste and weak smell, and are readily soluble in
water.
The neutral sulphones and sulphone like compounds obtained in the form of
black inodorous bodies are also readily pulverized when dry, they are readily
soluble in any of the solvents above described, nearly insoluble in alcohol, and
insoluble in water, but become readily soluble in water when combined with the
acid alkali salts (sulphonic acid salts).
In the production of these bodies the proportion of sulphonic acids obtained
relatively to the sulphones will, in a measure, depend upon the mode of procedure..
When operating at high temperature the preparation of soluble sulphonic acids.
obtained is reduced, consequently the solubility in water of the final product is
correspondingly reduced, the proportion of sulphonic acids present in the compound
determines therefore the solubility in water of the latter.
Having now particularly described and ascertained the nature of my said inven-
tion, and in what manner the same is to be performed, I declare that what I
claim is :--
1. The manufacture of a product easily soluble in water and essentially con-
sisting of sulphonic acid salts, by extracting with the aid of alcohol (ethylic or
other alcohols) or similar solvents the neutralized reaction mixture obtained by the
action of sulphuric acid on mineral or similar oils, substantially as and for the
purpose set forth.
2. The separation of the inorganic salts by washing out with water the residue
remaining after the removal of the sulphonic acid salts and the simultaneous
production of sulphone-like compounds insoluble in water, substantially as set
forth.
3. The manufacture of a product insoluble in water and essentially consisting of
sulphone-like compounds by extracting the reaction mixture formed by the action
of sulphuric acid on mineral or similar oils containing sulphur with the aid of
benzine, chloroform or similar solvents, prior to or after the extraction by alcohol
(ethylic or other alcohols), substantially as set forth.
Dated this 21st day of December 1893
HASELTINE, LAKE & Co.,
45, Southampton Buildings, London, W.C., Agents for the Applicant.