Manufacture of Phenetidine-sulphonic Acid and its Salts, as also of Acetyl Derivatives of the latter.
Year: 1897

page_text: COMPLETE SPECIFICATION.
Manufacture of Phenetidine-sulphonic Acid and its Salts, as also of
Acetyl Derivatives of the latter.
I, HAROLD IMRAY, of No. 28 Southampton Buildings, Chancery Lane, in the County
of London, Chartered Patent Agent, do hereby declare the nature of this invention
(which has been communicated to me from abroad by F. Hoffmann-La Roche & Co.,
of Basle, Switzerland, Manufacturing Chemists) and in what manner the same is to
be performed, to be particularly described and ascertained in and by the following
statement:-
My correspondents have discovered that in treating phenetidine with concentrated
sulphuric acid, phenetidine-sulphonic acid is produced. This as yet unknown
compound can be directly employed in medicine for the treatment of various diseases
and can also, after conversion into its metallic salts, be employed as initial product"
for the production of acetyl derivatives, which can be employed in medicine as
antipyretic substances soluble in water.
1. MANUFACTURE OF PHENETIDINE-SULPHONIC ACID AND ITS SALTS.
The following method will serve as an example: Phenetidine is slowly introduced
into from two to three times its weight of concentrated sulphuric acid or fuming
sulphuric acid containing 10 p. c. anhydride; a considerable rise of temperature
ensues, and the phenetidine sulphate, which at first separates is gradually dissolved.
again.
The heat generated by this reaction is sufficient to partially form phenetidine-
sulphonic acid; but the sulphonation is only completed on heating for a length of
time to from 100° to 120° C., or for a shorter time to a higher temperature.
In either case the mass becomes suddenly solid by the separation of the acid
produced.
In the reaction-product no phenetidine can be found by means of soda lye.
The product is mixed with water and washed therewith.
For its farther purification the phenetidine-sulphonic acid is converted into a salt,
such as a sodium salt, from which it is again separated by acid.
Phenetidine-sulphonic acid is a crystalline body which is white when pure; it is
soluble with great difficulty in cold water and alcohol, and not at all in ether..
For the production of the salts, the acid is either saturated directly with the base,
or it is converted by double decomposition.
The salts, which are mostly unstable, coloured, and readily soluble in water, can be
obtained in a very pure condition by precipitation from their aqueous solution by
means of alcohol.
For the production of the sodium salt, more especially, the solid acid for instance
is saturated with soda lye, or a solution of carbonate of soda, and the salt is
precipitated by means of alcohol or other precipitant acting in a similar manner.

page_text: II. PRODUCTION OF THE ACETYL DERIVATIVES.
The following serves as an example:-
Equal parts of sodium phenetidine-sulphonate and glacial acetic acid (or a
corresponding quantity of acetic anhydride) is heated to boiling point for several
hours in a reflux apparatus; the excess of acetic acid present is then separated as
much as possible by distillation, and the reaction-product is dissolved in a small
quantity of water, is then filtered and precipitated by strong alcohol. Or the
aqueous solution can be precipitated by means of a mixture of ether and alcoho,
but in the latter case the product will have to be purified by boiling with strong
alcohol.
The alcobo will dissolve any sodium acetate that may be present.
The final product consists of a reddish-white micro-crystalline hygroscopic body
which is easil, :oluble in water, less easily in alcohol, and insoluble in ether.
The phenetiine-sulphonic acid is only separated on boiling with mineral acids,
acetic acid being generated.
The employment of the sodium acetyl phenetidine-sulphonate as an antipyretic
agent shows, as compared with phenacetine, the advantage, that it is soluble in water
and therefore of more rapid action.
In a similar manner the acetyl-derivatives of the other metallic salts of phenetidine-
sulphonic acid can be prepared.
Having now particularly described and ascertained the nature of this invention
and in what manner the same is to be performed I declare that what I claim is :-
1. The process for the manufacture of phenetidine-sulphonic acid consisting in
treating plenetidine with concentrated or fuming sulphuric acid and purifying the
reaction product by its conversion into salts and separation therefrom by means of
acid, substantially as described.
2. The process for the manufacture of the salts of phenetidine-sulphonic acid
referred to in the first claim, consisting in converting the same into salts soluble in
water either by direct combination with bases, or by double decomposition, which
salts are then purified by treatment with a precipitant such as alcohol, substantially as
described.
3. The conversion of the metallic salts of phenetidine-sulphonic acid referred to in
the second claim, into acetyl derivatives by acetylising the phenetidine-sulphonates,
such as the sodium phenetidine-sulphonate by means of acetic anhydride, or glacial
acetic acid, and freeing the reaction-product by means of a suitable precipitant such
as alcohol, from the metallic acetate, such as sodium acetate that may have been
produced, substantially as described.
4. As new manufactures the phenetidine-sulphonic acid and its metallic salts,
produced as set forth in the first and second claims, and the acetyl derivatives of the
metallic salts of phenetidine-sulphonic acid produced as set forth in the third claim.
Dated this 14th day of June 1897.
ABEL & IMRAY,
Agents for the Applicant.