A New Compound or Derivative of Para-Tolyldimethylpyrazolon and Process for Obtaining the Same.
Year: 1892

page_text: A New Compound or Derivative of Para-Tolyldimethylpyrazolon
and Process for Obtaining the Same.
We, LUDWIG FRIEDRICH RIEDEL, Manufacturing Chemist, and HERMANN
THOMS, Doctor of Philosophy both of 12 and 13 Gericht Strasse Berlin, Germany,
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 :-
This invention relates to a certain compound or derivative of para-tolyldimethyl-
pyrazolon, CH,,N,O, and to a process for the manufacture of the same.
Hitherto the faculty of this body to form salts does not appear to have been
investigated.
We have found, that the said body combines readily with salicylic acid, so as
to form a crystallisable and well-defined salt, which possesses marked therapeutic
properties and is therefore applicable for medicinal purposes.
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For obtaining this salicylate, we commence by preparing the para-tolyl-dimethyl-
pyrazolon C,HN,O, for which purpose para-tolylhydrazin C,H,N,H, and aceto-
acetic ether CHO, may be used. When brought together in equimolecular
proportions, these two raw materials combine to form the compound C HN,O,
while water is being separated, which compound, on being heated, gives off alcohol
and yields the para-tolyl-methyl-pyrazolon CH₁N,O. When the latter is
heated with methyl-iodide and methyl-alcohol, it yields para-tolyl-dimethyl-
pyrazolon CH, N₂O.
This base is now fused together with salicylic acid in equimolecular proportions,
in order to obtain the salicylate which forms the subject of our invention.
In carrying out the above process, we mix 1.25 kilos. of para-tolylhydrazin with
1.5 kilos. of aceto-acetic ether, thereby causing a rise of temperature and separation
of water, which is scooped off. The residue, we heat on the water bath for about
3 hours. There remains the para-tolylmethylpyrazolon CH,N,O in the shape
of a granular crystalline mass, which is washed with ether, dissolved in a small
quantity of alcohol and heated with 15 kilos. of methyl-iodide in a closed retort
and at a pressure of 7 atmospheres, for about 8 hours.
The product thus formed is separated from the remaining methyl-iodide (that
which has not taken part in the reaction) and from the methyl-alcohol, by distil
lation. The residue containing the said product is dissolved in water, rendered
slightly alkaline, mixed with carbon tetra-chloride or with chloroform, and the
mixture shaken. The separated water, now containing dissolved p-tolyldimethyl-
pyrazolon, is evaporated, and the residue is recrystallised from acetic ether. Of
the para-tolyldimethyl-pyrazolon thus prepared (C₁,H,N,O), and whose melting
point is at 135° C., we take 1 kilo. and melt it together with 0.7 kilos. of salicylic
acid over a water bath. The oil thus obtained solidifies gradually and is then
recrystallized from acetic ether or alcohol.
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The salicylate of para-tolyldimethylpyrazolon produced in this manner, C₁,H,,1 N,O.
C,HO, forms colourless tough crystals which melt at 101-102 degrees centigrade.
It is sparingly soluble in water, but easily in alcohol, ether and acetic ether, and
yields salicylic acid, when brought together with a strong acid, such as sulphuric
acid. If brought together with a strong base, such as a solution of caustic soda,
it yields para-tolyldimethyl-pyrazolon.
The salicylate of para-tolyldimethylpyrazolon, is a new product, which we call
tolysal, and which has a very remarkable effect in some painful nervous derange-
ments or neuralgic pains, different from that of other known remedies.

page_text: The new compound is therefore chiefly applicable as a curative agent, but may
be used also as an antiseptic for certain industrial purposes.
Having now particularly described and ascertained the nature of the said inven-
tion, and in what manner the same is to be performed, we declare that what we
claim is :-
1. As a new product of manufacture, the salicylate of para-tolyldimethyl-
pyrazolon, also called tolysal, which, when in a pure condition, crystallises easily,
melts at 101 to 102° C., is sparingly soluble in water, but easily soluble in alcohol,
ether and acetic ether, and which yields salicylic acid, when brought together with
a strong acid, such as sulphuric acid, and para-tolyldimethylpyrazolon, when
brought together with soda solution.
2. The process for obtaining salicylate of para-tolyldimethylpyrazolon, which
consists in first producing the para-tolyldimethylpyrazolon, by mixing paratolyl-
hydrazin with aceto-acetic ether, heating the product, methylizing the para-
tolylmethylpyrazolon thus obtained, and subsequently melting the latter together
with salicylic acid in molecular proportions.
Dated this 27th day of October 1892
FAIRFAX & WETTER,
433, Strand, London, Agents for the Applicants.