The Manufacture or Production of Acidyl Salicylic Acids.
Year: 1899

page_text: Date of Application, 1st May, 1899
Complete Specification Left, 25th Jan., 1900-Accepted, 3rd Mar., 1900
The Manufacture or Production of Acidyl Salicylic Acids.
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings, Chancery
Lane, in the County of London, Patent Agent, do hereby declare the nature of this
invention to be as follows :-
My foreign correspondents discovered some time since that acetyl salicylic acid,
having the formula CH
OCOCH,
can be obtained by treating salicylic acid, or its
COOH
salts, with acetic anhydride, or with acetyl chloride, and that this acetylized acid
exhibits valuable therapeutical properties.
My foreign correspondents have now found that other acidyl derivatives of salicylic
acid which contain, instead of acetyl, other fatty acidyl radicles, also exhibit valuable
therapeutic properties, and that these acidyl derivatives, which were hitherto unknown,
can be obtained in a manner analogous to the above mentioned method for producing
acetyl salicylic acid, viz. :—by treating salicylic acid or its salts with the anhydrides
or chlorides of the respective fatty acids, such as propionic acid, butyric acid,
valeric acid, or the like. My foreign correspondents have further found, that on
producing acidyl salicyclic acids, it is more profitable to perform the reaction in the
presence of condensing agents, such as concentrated sulphuric acid, zinc chloride,
sodium acetate, or the like. If, for instance, acetic anhydride is allowed to act
on salicylic acid in the presence of one of such condensing agents, according to
recent researches of my foreign correspondents, a larger yield of acetyl salicylic
acid is obtained than is the case if the reaction is performed without the addition of
condensing agents.
In order to illustrate the production of the new acidyl derivatives of salicylic acid,
the following examples are given, the parts being by weight.
EXAMPLE A.
To a solution prepared by beating a mixture of 100 parts of salicylic acid with 200
parts of propionic-acid anhydride on a water-bath, 1 part of concentrated sulphuric
acid (of 66 degrees Baume) is added. The reaction sets in immediately, and will be
finished after heating the mixture for about one hour on a water-bath. On distilling
off the unchanged propionic anhydride, the pure propionyl salicylic acid separates
from the reaction mixture in the shape of small white and glittering leaves," which
nelt at about 95 degrees Centigrade, and are soluble with difficulty in water.
The process proceeds in an analogous manner if, instead of propionic anhydride,
the anhydrides of other fatty acids are employed. Thus, for instance, from butyric
anhydride, the butyryl salicylic acid, which melts at from 78 to 79 degrees Centigrade,
from valeric anhydride, the valeryl salicylic acid melting at from 87 to 89 degrees
Centigrade is obtained.

page_text: The production of the new acidyl compounds with the acid of the chlorides of the
respective acids is illustrated by the following:
EXAMPLE B.
A mixture prepared from 25 parts of salicylic acid and 20 parts of propionyl
chloride is heated, for several hours, in a vessel which is provided with a reflux
condenser. Subsequently, the unchanged propionyl chloride is distilled off with the
nid of a water-bath. The white crystalline mass thus obtained is purified by a
recrystallization from dry chloroform, the above described propionyl salicylic neid
being thereby obtained in a pure state.
My foreign correspondents wish to point out that they do not intend to conline
themselves to the particulars given in the above examples, as these are merely
typical, and can be varied within wide limits, without altering thereby the nature of
the present invention. Thus, for instance, instead of the free salicylic acid, the salts
of this acid can likewise be employed.
Boted his bat duofo Lean
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings,
Chancery Lane, in the County of London, Patent Agent, 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:-
In the Specification of Letters Patent No. 27088, dated December 22nd 1898,
OCOCH
it is stated that acetyl salicylic acid, having the formula
COOH,
can be obtained by treating salicylic neid, or its salts, with neetic anhydride, or
with acetyl-chloride, and that this acetylized acid exhibits valuable therapeutic
properties.
My foreign correspondents have now found that other acidly derivatives of
salicylic acid, which contain, instead of acetyl, other fatty acidyl radicals, also
exhibit valuable therapeutic properties, and that these neidyl derivatives, which were
hitherto unknown, can be obtained in a manner analogous to the above mentioned
method for producing acetyl-salicylic acid, vi, by treating salicylic acid, or its salts.
with the anhydrides or chlorides of the respective fatty acids, such as propionic
neid, butyric acid, valeric acid, or the like.
My foreign correspondents have further found that, on producing neidyl-salicylic
acids, it is more profitable to perform the reaction in the presence of condensing
agents, such as concentrated sulphuric acid, zine chloride, sodium acetate, or the
like. If, for instance, acetic anhydride is allowed to act on salicylic acid in the
presence of one of such condensing agents, according to recent researches of my
foreign correspondents, a larger yield of acetyl salicylic acid is obtained than is
the case if the reaction is performed without the addition of condensing agents.
In order to illustrate the production of the new acidyl derivatives of salicylic acid.
the following examples are given, the parts being by weight.

page_text: The production of the new acidyl compounds with the aid of the chlorides of the
respective acids is illustrated by the following:-
EXAMPLE B.
A mixture prepared from 25 parts of salicylic acid and 20 parts of propionyl
chloride, is heated for several hours in a vessel which is provided with a reflux
condenser. Subsequently, the unchanged propionyl-chloride is distilled off with the
aid of a water-bath. The white crystalline mass thus obtained is purified by a
recrystallization from dry chloroform, the above described propionyl salicylic acid
being thereby obtained in a pure state.
My foreign correspondents wish to point out that they do not intend to confine
themselves to the particulars given in the above examples, as these are merely typical,
and can be varied within wide limits without altering thereby the nature of the
present invention. Thus, for instance, instead of the free salicylic acid, the salts of
this acid can likwise he employed.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed, as communicated to me from
abroad, I declare that what I claim is :-
1. The improvement in the production of acetyl salicylic acid consisting in per-
forming the re-action of acetic anhydride on salicylic acid, or its salts, in the presence
of suitable condensing agents, substantially as herein before described.
2. The process for the production of neidyl derivatives of salicylic acid, which
process consists in allowing the anhydrides or chlorides of propionic acid, butyric-
acid, valerie acid, or the like higher homologues of acetic acid, to act on salicylic
acid, or salts thereof, with or without the presence of suitable condensing agents,
substantially as herein before described.
3. As new articles of manufacture, the new bodies obtainable according to the
processes, hereinbefore described and claimed.
4. The use of the new bodies herein before described and claimed for therapeutic
purposes.
Unied this 95th day of tannery 1000