Medicinal Preparations.
Year: 1897

page_text: Medicinal Preparations.
I, SAMUEL THEODOR HERMANN KARL ENDEMANN, of 410, Green Avenue, Brooklyn,
in the County of Kings and State of New York, in the United States of America,
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 "foliow-
ing statement :-
Many medicinal phenol-like substances of the aromatic series of organic com-
pounds possess properties which prevent their free application for the reason that
they act as irritants upon the mucous membranes of the body. It is known that
such substances lose their irritating properties by conversion into esters. The
methyl, ethyl and similar ethers of such phenol-like bodies possess, however, such
great stability and are also so insoluble in water, that where efforts had been made
to investigate their action upon the human system, it was found that the inherent or
characteristic action of the original phenols was entirely obliterated or changed.
I have discovered that the ethers obtained by the action of mono-chlorhydrin upon
the sodium compounds of these phenol-like bodies possess properties which make
them very desirable compounds for medicinal use. Such ethers do not possess the
high degree of insolubility in water and are, therefore, more easily decomposed than
the ethers before mentioned, in fact, they are invariably more soluble in water than
the phenol-like bodies from which they are prepared, and thus absorption is facilitated
and the irritating action is mitigated or entirely removed. Bodies so formed possess
a bitter taste and frequently a specific flavour denoting their source or origin.
Of the substances which I have thus converted into ethers, I mention the follow-
ing-guaiacol, eugenol, carvacrol, borneol, alphanaphtol, betanaphtol, 2-3 dioxy-
naphtalene, thymol and the esters of aromatic oxy-acids, like oil of wintergreen or
glycerol-salicylic acid ester.
Medicinal preparations which belong to the class of which phenoxacetic acid is the
representative, I convert into esters by the action of mono-chlorhydrin upon the
sodium salts of such acids.
In the preparation of these ethers or esters, I use the ingredients in molecular
proportions. Thus, I use for one molecule of a phenol-like substance as many
molecules of sodium hydrate as the phenol-like substance contains hydroxyl groups,
and of mono-chlorhydrin a quantity equivalent to the sodium hydrate employed. In
the preparation of the esters of the acids belonging to the group of the phenoxacetic
acid, I use for one molecule of mono chlorhydrin, one molecule of the sodium salt of
the respective acid.
The ingredients are thoroughly mixed in all these cases and heat applied slowly
until the re-action takes place, which becomes evident from the formation of salt or
the sudden rise of temperature of the mass; the heating is then continued to 140 or
150 degrees Centigrade until the alkaline re-action disappears whereupon the process
is complete. In all such cases where the comparative insolubility of the product
permits, some glycerin may be added during the process to facilitate stirring, and
thus prevent overheating. The use of glycerin is omitted whenever the product
possesses considerable solubility in water, as for instance in the case of diglycerol

page_text: salicylate or the ether of 2.3 dioxynaphtalene. The use of glycerin is, in general,
omitted whenever two or more glycerin radicles enter the molecule.
In all such cases where the substances in re-action possess boiling points consider-
ably higher than the temperature necessary to complete the re-action, the operation
may be performed in open vessels, but it must be performed in autoclaves or stills
whenever partial vaporization is to be expected.
All such appliances must be supplied with means for effectually stirring the mass
throughout the operation. The appliances may be heated either by steam or an oil
bath to secure more equal distribution of heat.
To more fully illustrate the method of producing ethers, I will proceed to describe
in detail the operation of producing the guaiacol ether:
124 parts of guaiacol are mixed with 40 parts of finely ground sodium hydrate and
to this are added 111 parts of mono-chlorhydrin and some glycerin, the latter being
used to facilitate the stirring of the mass. The whole is then gradually heated while
continually stirring. Toward 120 degrees Centigrade, the re-action commences, but
the temperature of the bath is gradually raised to from 140 to 150 degrees Centigrade.
The reaction is complete when the mass does not show an alkaline re-action, or at
least gives so slight an alkaline re-action, that it can be removed by the addition of
a very small quantity of mono-chlorhydrin.
To remove the salt which has been formed during the process, as well as the
glycerin previously added, the mass after cooling, is treated with water which takes
up these impurities, leaving the undissolved ether behind in the form of a liquid. If
the ether is placed into a still and the water removed by distillation, the oily residue
will crystallize on cooling, especially upon the addition of some crystals from a
previous operation.
To prepare diglycerol salicylate, I proceed as follows-One molecule, or 212 parts
of glycerol salicylate as it is obtained from the process of acting upon a solution of
salicylic acid in glycerin with hydrochloric acid, is thoroughly mixed with 111 parts
of mono-chlorhydrin and 40 parts of finely pulverized sodium hydrate. Under
continuous stirring, the mass is gradually heated to from 140 to 150 degrees
Centigrade, until the re-action is complete. After cooling, the salt formed in the
re-action is removed by the addition of alcohol. The ether thus formed is a liquid
quite soluble in water and possesses an agreeable bitter taste.
The substances obtained by the process described above and derived from medicinal,
phenol-like substances are intended for medicinal use.
Having now particularly described and ascertained the nature of my said
invention and in what manner the same is to be performed I declare that what I
claim is
-
1. The herein described process for converting medicinal phenol-like bodies and
their derivatives into ethers or esters by the action of mono-chlorhydrin upon their
sodium compounds at an elevated temperature; said temperature being gradually
raised to from 140 to 150 degrees Centigrade.
2. As new products, the substances which are the result of the action of the sodium
compounds of medicinal phenol-like bodies or derivatives upon mono-chlorhydrin,
which are characterised by the facts that a corresponding phenol-like body can be
liberated therefrom by the action of dilute acids at an elevated temperature such as
is usually employed for the decomposition of esters and ethers and that they are
soluble in water, alcohol and ether and have a bitter taste.
HARRIS & MILLS,
23, Southampton Buildings, London, W.C., Agents.