Improvements in the Production of Pyrazolone Derivatives.
Year: 1892

page_text: Date of Application, 15th Aug., 1892
Complete Specification Left, 15th May, 1893-Accepted, 22nd July, 1893
PROVISIONAL SPECIFICATION.
[Communicated from abroad by THE FARBWERKE vormals MEISTER LUCIUS
AND BRUNING, of Hoechst a/ Main, in the Empire of Germany, Chemical
Manufacturers.]
Improvements in the Production of Pyrazolone Derivatives.
I, OLIVER IMRAY of No. 28 Southampton Buildings in the County of London,
Chartered Patent Agent, do hereby declare the nature of this. invention to be as
follows:-
By the action of para-ethoxy-phenyl-hydrazine upon acetyl-acetic ether and its
homologues there are easily obtained ethoxylised methylphenylpyrazolones while
water and alcohol are eliminated.
Thus there is obtained by condensation of para-ethoxy-phenyl-hydrazine with
acetyl-acetic ether the para-ethoxy-phenylmethylpyrazolone in accordance with the
equation:

page_text: PRODUCTION OF PARA ETHOXY-ANTIPYRINE FROM
PARA-ETHOXY-PHENYL-
METHYL-PYRAZOLONE CARBONIC ACID.
52 parts by weight of para-ethoxy-phenyl-methyl-pyrazolone-carbonic acid,
15 parts by weight of methyl-alcohol and 2.8 parts by weight of iodide of methyl
are heated in a melting tube for 24 hours on the water bath. The methyl alcohol
is then removed by distillation, the residue is heated at from 165° to 170° C. until
the elimination of CO, has ceased. The resinous residue is taken up in hot water;
after having cooled the solution is filtered off from the resin, rendered alkaline by
means of soda lye and shaken out at about 60° C. with benzene. The benzene
solution is dried and filtered. After the benzene has evaporated there remains a
residue which after a time assumes a crystalline form, and melts at from
89° to 90° C., after repeated recrystallisation from acetic-ether. It is of very easy
solubility in water and alcohol, forms a green nitroso compound and in aqueous
solution it assumes dark-red coloration on the addition of ferric chloride.
Analysis and properties show that the novel body is para-ethoxy-antipyrine.
PRODUCTION OF PARA-ETHOXY-HOMO-ANTIPI KINE
acid,
a) From para-ethoxy-phenyl-methyl-pyrazolone-carbonic acid.
52 parts by weight of para-ethoxy-phenyl-methyl-pyrazolone-carbonic
15 parts by weight of alcohol and 3.07 parts by weight of iodide of ethyl are
heated in a melting tube for 24 hours on the water bath.
The ethylalcohol is then distilled off, the residue heated at from 165° to 170° C.
until the elimination of CO, ceases. The resinous residue is taken up in hot
water; after having cooled the solution is filtered off from the resin, rendered
alkaline by means of soda-lye and shaken out at about 60° C. with benzene. The
benzene-solution is dried and filtered. After the benzene has evaporated there
remains a residue which after some time takes crystalline form and melts at 121°
to 122° C. after repeated recrystallisation from acetic-ether. It is of very ready
solubility in water and alcohol, forms a green nitroso compound, and in aqueous
solution assumes dark red coloration on the addition of ferric chloride.

page_text: ABEL & IMRAY,
Agents for the Applicant.
COMPLETE SPECIFICATION.
Improvements in the Production of Pyrazolone Derivatives.
I, OLIVER IMRAY, of No. 28 Southampton Buildings in the County of London,
Chartered 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 :-
By the action of para-ethoxy-phenyl-hydrazine upon acetyl-acetic ether and its

page_text: homologues there are easily obtained ethoxylised methylphenylpyrazolones while
water and alcohol are eliminated.
Thus there is obtained by condensation of para-ethoxy-phenyl-hydrazine with
acetyl-acetic ether the para-ethoxy-phenylmethylpyrazolone in accordance with the.
equation:
C,H,O CH, NH NH, + CH, CO CH,CO, CH =
=H,O + C,H,OH + C,H,O C,H, - N - N
PRODUCTION OF ETHOXYPHENYLMETHYLPYRAZOLONE FROM ETHOXY PHENYL-
HYDRAZINE AND ACETONE DICARBONIC ACID.
i
206 parts by weight of crude acetone dicarbonic acid corresponding to 143-6 parts"
by weight of pure acetone dicarbonic acid are dissolved in the eight fold quantity
of water, the solution is filtered and to it is added a tenth part by weight of
concentrated hydrochloric acid. In this solution there are dissolved, while agitated,
152 parts by weight of ethoxy-phenyl-hydrazine. When the ethoxy-phenyl-

page_text: hydrazine has dissolved, the para-ethoxy-phenyl-pyrazolone carbonic acid separates
in the form of a crystalline powder. After sucking off the mother lye, the acid is
purified by repeated dissolving and fractional precipitation by means of carbonate
of soda. The acid crystallises from diluted alcohol in the form of brilliant leaflets,
which melt at 164° C. under decomposition. The acid is soluble with difficulty in
water, easily in alcohol and diluted acids.
When the acid is heated to 164° C., carbonic acid splits off and it transforms
smoothly into para-ethoxy-phenyl-methyl-pyrazolone (1.3.5) melting point 147° C.
which, by methylising, can be converted into para-ethoxy-antipyrine.
PRODUCTION OF
PARA-ETHOXY-ANTIPYRINE FROM
PARA-ETHOXY-PHENYL-
METHYL-PYRAZOLONE CARBONIC ACID.
52 parts by weight of para-ethoxy-phenyl-methyl-pyrazolone carbonic acid,
15 parts by weight of methyl alcohol and 2-8 parts by weight of iodide of methyl
are heated in a melting tube for 24 hours on the water bath. The methyl alcohol
is then removed by distillation, the residue is heated at from 165° to 170° C. until
the elimination of CO, has ceased. The resinous residue is taken up in hot water;
after having cooled, the solution is filtered off from the resin, rendered alkaline by
means of soda lye and shaken out at about 60° C. with benzene. The benzene
solution is dried and filtered. After the benzene has evaporated, there remains a
residue which after a time assumes a crystalline form, and melts at from 89°
to 90° C., after repeated recrystallisation from acetic-ether.
It is of very easy solubility in water and alcohol, forms a green nitroso compound
and in aqueous solution it assumes dark red coloration on the addition of ferric
chloride.
Analysis and properties show that the novel body is uara-ethoxy-antinvrine
PRODUCTION OF PARA-ETHOXY-HOMO-ANTIPYRINE
a) From para-ethoxy-phenyl-methyl-pyrazolone carbonic acid.
5-2 parts by weight of para-ethoxy-phenyl-methyl pyrazolone carbonic acid,
15 parts by weight of alcohol and 3-07 parts by weight of iodide of ethyl are
heated in a melting tube for 24 hours on the water bath.
The ethyl alcohol is then distilled off, the residue heated at from 165° to 170° C.
until the elimination of CO, ceases. The resinous residue is taken up in hot water;
after having cooled, the solution is filtered off from the resin, rendered alkaline by
means of soda lye and shaken out at about 60° C. with benzene.
The benzene solution is dried and filtered.
After the benzene has evaporated there remains a residue which after some time
takes crystalline form and melts at 121° to 122° C. after repeated recrystallisation
from acetic ether.
It is of very ready solubility in water and alcohol, forms a green nitroso
compound, and in aqueous solution assumes dark red coloration on the addition of
ferric chloride.
Analysis and properties show the novel body to be para-ethoxy-homo-antipyrine.
b) From para-ethoxy-phenyl-methyl-pyrazolone.
85 parts by weight of para-ethoxy-phenyl-methyl-pyrazolone

page_text: distilled off, the residue, being coloured brown by the iodine, is taken up in water
and soda lye and is shaken out hot with benzene. After the benzene has evaporated
there remains a dark brown mass assuming crystalline form on cooling, which is
extracted with cold water. The solution is filtered off from the brown resin which
remains undissolved, to this is added soda lye and it is shaken out with benzene. The
crystalline mass remaining after evaporation of the benzene is recrystallised twice
from acetic ether; melting point at 121° to 122° C.
The aqueous solution of the para-ethoxy-homo-antipyrine assumes a dark red
colour on the addition of ferric chloride.
PRODUCTION OF ETHOXY-ETHYL-ANTIPYRINE.
24-6 parts by weight of para-ethoxy-phenyl-methyl-ethyl-pyrazolone, the 24 fold
quantity of methyl alcohol and 14-2 parts by weight of iodide of methyl are heated
in a melting tube for 24 hours at from 130° to 140° C. After opening the tube,
there will be found on its bottom a small quantity of crystals of the melting
point 193° C. and soluble with difficulty.
The solution is filtered off from these crystals, the methyl alcohol distilled off,
the residue taken up in hot water, soda lye is added and the substance is shaken out
with benzene.
After evaporation of the benzene, there remains a crystalline mass which is
obtained in relatively pure form by dissolving in diluted hydrochloric acid, filtering,
supersaturating with soda lye, shaking out with benzene and evaporation of the
same.
Recrystallised from alcohol it has the melting point of 105° to 106° C.
The para-ethoxy-ethyl-antipyrine is easily soluble in alcohol and diluted acids,
with greater difficulty in cold water and ether; in alkalies it is insoluble.
Having now particularly described and ascertained the nature of this inven-
tion and in what manner the same is to be performed, I declare that what I
claim is
1. The production of para-ethoxy-phenyl-methyl-pyrazolone by condensation of
para-ethoxy-phenylhydrazine with acetone dicarbonic acid or its ethers.
2. The production of para-ethoxy-antipyrine by methylising para-ethoxy-phenyl-
methyl-pyrazolone carbonic acid and subsequently splitting off carbonic acid.
3. The production of para-ethoxy-homo-antipyrine by ethylising the para-ethoxy-
phenyl-methyl-pyrazolone carbonic acid and subsequently splitting off carbonic
acid or by ethylising the para-ethoxy-phenyl-methyl-pyrazolone.
4. The production of para-ethoxy-phenyl-methyl-ethyl-pyrazolone by the action
of ethyl-acetyl-acetic-ether upon para-ethoxy-phenyl-hydrazine.
5. The production of para-ethoxy-ethyl-antipyrme by methylising the para-
ethoxy-phenyl-methyl-ethyl pyrazolone.

page_text: 6. The para-ethoxy-phenyl-methyl-pyrazolone,
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antipyrine,
homo-antipyrine,
phenyl-methyl ethyl pyrazolone,
ethyl-antipyrine,
produced as herein described