Manufacture of New Derivatives of Amido-1-alphyl-2 alkyl- 5-pyrazolones..
Year: 1896

page_text: Date of Application, 11th Apr., 1896
Complete Specification Left, 11th Jan., 1897-Accepted, 20th Feb., 1897
Manufacture of New Derivatives of Amido-1-alphyl-2 alkyl-
5-pyrazolones..
I, OLIVER IMRAY, of No. 28 Southampton Buildings, Chancery Lane, in the
County of London, Chartered. Patent-Agent, do hereby declare the nature of this
invention to be as follows:-
Of the derivatives of amido-1 alpbyl-2 alkyl-5-pyrazolones only the 4-acetamido-
1-phenyl-2.3-dimethylpyrazolone.has hitherto been known.
My foreign correspondents obtain new derivatives of amido-1 alphyl-2-alkyl-
3-methyl-5-pyrazolone and 1-p-amido-phenyl-2-alkyl 3-methyl-5-pyrazolone, by
introducing alcohol- and acid radicles into these compounds. They obtain the last
mentioned compound 1-p-amido-phenyl-2-alkyl-3-methyl-5-pyrazolone, or its alkoyl
derivatives hy treating the derivatives of 1-p-alkoyl-amido-phenyl-3-methyl-
5-pyrazalone, which contain alcohol or. acid radicles linked with the oxygen atom,
the general formula of which is
with alkyliodides or their equivalents and then with alkalies. The alkoyl-amido
derivatives thus obtained can be converted into the corresponding amido-compounds
by the hydrolytic action of acids.
Like the previously mentioned derivatives of phenylpyrazolone they can also
obtain analogous compounds which contain another aromatic radicle instead of
phenyl.
The new alcohol and alkoyl derivatives of amido-1-alphyl-2-alkylpyrazolone are,
without exception, basic compounds forming salts with acids.
The following are examples of the-manufacture of some derivatives of amido-
1-phenyl-2-methyl 5-pyrazolone.
1. FORMYL DERIVATIVE OF THE 1-PHENYL-2.3 DIMETHYL-4 AMIDO-
5-PYRAZOLONE.
This compound is formed by heating the amido compound with formic acid of
about 50 per cent. The new product crystallises when suitably concentrated and
can be recrystallised from alcohol or toluene; it melts at 189° C.

page_text: 3. URETHANE OF THE SAME AMINE.
This compound is obtained by combining the amido compound with ethyl-chloro-
carbonate in presence of alkali-carbonate in aqueous solution, and cooling during
the reaction. Crystallised from alcohol the urethane forms crystals which melt
at 206° C.
4. CARBAMIDE OF THE SAME AMINE.
48 parts by weight of hydrochlorate of the amido compound and 17 parts
by weight of cyanate of potassium are heated in an aqueous solution, from which
the carbamide crystallises out in laminæ not easily soluble in water; nor is it easily
soluble in alcohol or ether.
.
5. DIMETHYL-DERIVATIVE OF THE SAME AMINE
is obtained by methylation of the same, either by the action of methyl iodide, or
by heating with methyl alcohol and hydrochloric acid or hydrobromic acid or by
the action of the methylsulphate of an alkali or by heating with formic aldehyde.
For example, 1 part by weight of 1-phenyl-2.3-dimethyl-4-amido-5-pyrazolone is
heated with 1 part by weight of methyl alcohol and 14 parts by weight of methyl
iodide during one hour to 90° C.
After evaporation of the methyl alcohol, the base is set free from the product of
the reaction by means of alkali and extracted with benzene. It is purified by
crystallisation from ethyl acetate and ligroine; it melts at 108° C. and is easily
soluble in water, alcohol and benzene.
6. 1-P-ACETAMIDOPHENYL-3-METHYL-5-PYRAZOLONE
is obtained by combining p-acetamidophenyl-hydrazine with ethyl aceto-acetate
in equal molecular proportions or by the action of glacial acetic acid or acetic
anhydride upon p-amido-pyrazolone; in the latter case, however, other compounds
are simultaneously formed, among which a di-acetyl derivative, which is also
formed from the mono-acetyl derivative by further action of acetic anhydride.
The monoacetyl compound may be obtained as shewn in the following example:-
p-acetyl-amido-phenyl-bydrazine (1 mol.) and ethyl-aceto-acetate (1 mol.) are
heated in an alcoholic solution, then evaporated and heated to 140-150° C.
The product of the reaction gives, on crystallisation, from dilute alcohol,
p-acetamido-phenyl-pyrazolone melting at 197° C. This compound is quite
different from the product of the same name and described in the German
Patent No. 85,883, the formula and constitution of which are different.
7. ETHYLETHER OF 1 P-ACETAMIDO-PHENYL-METHYL-PYRAZOLONE.
The primary reaction of p-acetamido-phenyl-hydrazine with ethyl-aceto-acetate-
ester also takes place in an aqueous solution in presence of an acid; in this case,
however, besides acetamido-pyrazolone, a second compound is also to be found in
the product of the reaction; riz. the ethyl ether of acetamidopyrazolone which
crystallises from dilute alcohol in prisms, containing water of crystallisation and
melting at 117° C.; the anhydrous compound melts at 132° C.
8. ACETYLETHER OF 1 P-ACETAMIDO-PHENYL-METHYL-PYRAZOLONE.
This compound is obtained from I p-amido-phenyl-methyl-pyrazolone or from
the 1-p-acetamidopyrazolone by boiling with acetic anhydride or he shaking with

page_text: 12. 1 P-DIMETHYLAMIDOPHENYL-2.3-DIMETHYL-5-PYRAZOLONE.
This compound is obtained by the action of methyl iodide and methyl alcohol
upon the before mentioned compounds 1-p-acetylamidopyrazolone, acetylether of
acetamidopyrazolone, 1 p-amidopyrazolone and 1 p-amido-phenyl-2.3-dimethyl-
pyrazolone. The best result is obtained by heating 5 parts by weight of the latter
compound with 3.5 parts by weight of methyl iodide and 5 parts by weight of
methyl alcohol on a boiling water bath in a closed vessel.
The dimethylamidopyrazolone is separated from the product of the reaction,
after evaporating the methylalcohol, by addition of soda lye and shaking with
benzene.
The compound is purified by repeated crystallisation from ligroine and ethyl
acetate and obtained in form of lamine which melt at 134-135° C.

page_text: 14. URETHANE OF THE SAME AMINE
is obtained like the corresponding derivative of the isomeric base, (as already
mentioned in Example 3) it melts at 196° C.
Dated this 11th day of April. 1896.
ABEL & IMRAY,
Agents for the Applicants.
COMPLETE SPECIFICATION.
Manufacture of New Derivatives of Amido-1 alphyl-2 alkyl-
5 pyrazolones.
I, OLIVER IMRAY, of No. 28 Southampton Buildings, .Chancery Lane in the
County of London, Chartered Patent Agent, do hereby declare,the, nature, of..this
invention (as communicated to me from abroad by The Farbwerke vormals Meister
Lucius and Brüning, of Hoechst..a/Main, in the Empire of Germany, Chemical
Manufacturers) and in what, manner the same, is, to be performed, to be particularly
described and ascertained in and by the following statement:-
Of the derivatives of amido 1 alphyl 2 alkyl 5 pyrazolones only the 4 acetamido-
1 phenyl 2.3 dimethylpyrazoloue has hitherto been known.
My foreign correspondents obtain new derivatives of 4-amido 1 alphyl 2 alkyl
3 methyl 5 pyrazolone and 1 p-amido-phenyl 2 alkyl 3 methyl 5 pyrazolone, by
introducing alcohol- and acid-radicles into these compounds.
They obtain the last-mentioned compound 1 p-amido-phenyl 2 alkyl 3 methyl
5 pyrazolone, or its alkoyl derivatives by treating the derivatives of 1 p-alkoylamido-
phenyl 3 methyl 5 pyrazolone, which contain alcohol or acid radicles linked with
the oxygen atom, the general formula of which is
with alkyliodides or their equivalents and then with alkalies. The alkoylamido
derivatives, thus obtained.can be converted into the corresponding. amido.compounds
by the hydrolytic action.of acids.
The new alkyl and alkoyl-derivatives of amido 1-alphyl 2 alkylpyrazolone..are
without exception basic compounds, forming salts with acids.
The following are examples of the manufacture of some derivatives of 4.amido-
1 alphyl 2 alkyl 3 methyl 5 pyrazolones and 1 p-amido-phenyl 2 alkyl 3 methyl
5 pyrazolones.
1. DERIVATIVES OF 4 AMIDO 1 ALPHYL 2 ALKYL 3 METHYL 5 PYRAZOLONE.
1. Formylderivative of the 1 phenyl 2.3 dimethyl 4 amido 5 pyrazolone.-This
compound is formed by heating the amido compound with formic acid of about
50 per cent. The new product crystallises when suitably. concentrated.and can be
recrystallised from alcohol or toluene; it melts at 189° C.
2. Dibenzoyl derivative of the same amine is obtained by shaking the amido
compound with soda lye and benzoyl-chloride and cooling at the same time.
Crystallised from alcohol the compound melts at 188° C.

page_text: 3. Urethane of the same amine.-This compound is obtained by combining the
amido compound with ethyl chloro-carbonate in presence of alkali-carbonate in
aqueous solution, and cooling during the reaction. Crystallised from alcohol the
urethane forms crystals which melt at 206° C.
4. Carbamide of the same amine.-48 parts by weight of hydrochloride of the
amido compound and 17 parts by weight of cyanate of potassium are heated in an
aqueous solution, from which the carbamide crystallises out in laminæ not easily
soluble in water, alcohol or ether.
5. Dimethyl derivative (1 phenyl 2.3 dimethyl 4 dimethyl-amido 5 pyrazolone)
of the same amine is obtained by methylation.of the same; either by the action of
methyl iodide, or by beating with methyl alcohol and hydrochloric acid or
hydrobromic acid or by the action of the methyl-sulphate of an alkali or by heating
with formic aldehyde. For example, 1 part by weight of 1 phenyl 2.3 dimethyl
4 amido 5 pyrazolone is heated with 1 part by weight of methyl alcohol and
14 parts by weight of methyl iodide during one hour to 90° C.
After evaporation of the methyl alcohol, the base is set free from the product of
the reaction by means of alkali and extracted with benzene.
It is purified by crystallisation from ethyl acetate and ligroine; it melts
at 108° C. and is easily soluble in water alcohol and benzene.
After the extraction of the 4 dimethylamido derivative, an ammonium base
remains in the alkaline mother-lye in form of its iodide formed by further
methylation of 4 dimethylamido derivative; it is separated from the solution by
means of alkalies and can be transformed on being heated by itself, preferably
in vacuo, into the 4 dimethylamido derivative. Instead of the iodide, the free
ammonium base or another of its salts, carbonate or sulphate for instance, serves
the same purpose.
6. By ethylation of the amido derivative the 4 diethylamido derivative,
corresponding to the above 4 dimethylamido derivative may be obtained, which
melts at 95° C.
7. 1 alphyl 2 alkyl 3 methyl 4 dialkylamido 5 pyrazolones. By employing in
the above method of alkylation other 4 amido 1 alphy! 2 alkyl 3 methyl
5 pyrazolones instead of 4 amido 1 phenyl 2.3 dimethyl 5 pyrazolone and
methylating or ethylating the same, the corresponding 4 dialkylamido derivatives
may be obtained, of which may be mentioned.
1 phenyl 2 ethyl 3 methyl 4 dimethylamido 5 pyrazolone melting point
1. p-tolyl 2 methyl
104-5
107° C.
"
"
"
33
"
4 diethylamido
84
"
"
"
"
2 ethyl
"
4 dimethyl
99-100
"
"
"
"
"
4 diethyl
95-97
"
"
"
"
4 dimethyl
70-72
"
"
"
"
"
2 ethyl
1
»-
"
2 ethyl
4
107°
"
"
"
"
"
100-101
"
83-5
"
وو
"
1 o-tolyl 2 methyl
"
p-ethoxyphenyl 2 methyl 3 methyl 4 dimethylamido 5 pyrazolone,,
"
8. Monoalkyl and monoalkoyl derivatives of the 1 alphyl 2.3 dimethyl 4 amido
5 pyrazolones.-5 parts by weight of 1 phenyl 2.3 dimethyl 4 amido 5 pyrazolone
are heated for 3 to 4 hours to about 100° C. with 2.5 parts by weight of
ethylbromide and 2-5 parts by weight of alcohol; the latter is distilled off, the
residue is dissolved in water made alkaline, and the solution is extracted with
benzene. The benzene is distilled off, the residue is dissolved in water and stirred
with benzaldehyde in order to remove the unchanged 1 phenyl 2.3 dimethyl 4 amido
5 pyrazolone. The benzylidene compound thus formed is filtered off, then the
benzaldehyde is distilled with steam and the residual solution is treated with
benzoyl-chloride and soda-lye while it is being cooled. The benzoyl-compound of
the 4 monoethyl amido-derivative separates out, and has to be purified by
crystallisation from benzene, ligroine and alcohol (melting point 148° C.).

page_text: On boiling with hydrochloric acid the benzoyl compound is decomposed and the
monoethylamido derivative is obtained; (melting point 49° C.).
When boiled with acetic anhydride, the monoethyl-amido derivative produces
the 4 acetylmonoethylamido derivative; (melting point 119° C.)..
In a similar manner by methylating and benzoylating 1 phenyl 2.3 dimethyl
4 amido 5 pyrazolone, the 4 benzoylmonomethyl amido-derivative is obtained,
(melting point 137° C., which on being hydrolysed produces the 4 monomethyl-
amido-derivative, the picrate of which melts at 172° C.
From 1 p-tolyl 2.3 dimethyl 4 amidopyrazolone is obtained in a similar manner
the 4 benzoylmonoethylamido derivative; (melting point 106° C.) and from the
latter by hydrolysis the 4 monoethylamido-derivative which has a low melting
temperature and consequently crystallises with difficulty.
11. MANUFACTURE OF I I-AMIDOPHENYL 2.3 DIMETHYI. 5 PYRAZOLONE.
1. 1 p-acetamidophenyl 3 methyl 5 pyrazolone is obtained by combining p-acet-
amidophenyl hydrazine with ethyl-acetoacetate in equal molecular proportions,
or by the action of glacial acetic acid or acetic anhydride upon p-amidopyrazolone;
in the latter case, however, other compounds are simultaneously formed, among
which a diacetyl derivative, which is also formed from the mono-acetyl derivative
by further action of acetic anhydride. The mono-acetyl compound may be
obtained as shewn in the following example:-
p-acetylamidophenyl hydrazine (1 molecule) and ethyl acetoacetate (1 molecule)
are heated in an alcoholic solution, then evaporated and heated to 140° to 150° C.
The product of the reaction gives on crystallisation from dilute alcohol p-acet-
amidophenylmethyl pyrazolone melting at 197° C. This compound is quite
different from the product of the same name described in the German Patent
No. 85883, the formula and constitution of which are different.
2. Ethylether of 1 p-acetamidophenylmethyl pyrazolone.-The reaction of
p-acetamido-phenylhydrazine with ethyl acetoacetate also takes place in an aqueous
solution in presence of an acid; in this case, however, besides acetamidophenyl
methyl pyrazolone a second compound is also to be found in the product of the
reaction; viz. the ethylether of acetamido phenylmethylpyrazolone which crystal-
lises from dilute alcohol in prisms, containing water of crystallisation and melting
at 117° C.; the aubydrous compound melting at 132° C.
3. Acetylether of 1 p-acetamidophenylmethylpyrazolone.-This compound is
obtained from 1 p-amidophenylmethyl pyrazolone or from the I p-acetamidophenyl-
methyl pyrazolone by boiling with acetic anhydride or by shaking with acetic
anhydride in presence of soda-lye.
The acetylether separates out, crystallises in yellowish laminæ and melts
at 160° to 161°C.
It is easily soluble in benzene and chloroform, less soluble in ether or ligroïne.
4. Ethylcarbonic acid ether of p-acetamidophenylmethyl-pyrazolone. The
carbonate is obtained by the action of ethyl-chloro-carbonate upon p-acetamido-
phenylmethyl-pyrazolone in presence of soda lye. It crystallises from dilute
alcohol in needles or laminæ, which melt at 105° Č.
5.1 p-acetylamidophenyl 2.3 dimethyl 5 pyrazolone.-On heating the above
mentioned ethyl-acetyl- or ethyl carbonic-acid-ether of 1 p-acetamido phenyl
3 methyl 5 pyrazolone with methyl iodide in an indifferent solvent like benzene,
iodides of ammonium bases are formed, which by the action of alkalies or acids
split the alkyl or alkoyl from the oxygen and give the 1-p-acetylamido 2.3 dimethyl
5 pyrazolone. For example, 50 parts by weight of the above mentioned ethyl
carbonic-acid-ester are heated with 25 parts by weight of methyl iodide and
100 parts by weight of benzene for 12 hours to 100°C.
The iodide of the ammonium base thus formed is dissolved in water, made
alkaline with soda lye and heated and then the 1 p-acetylamidophenyl- 2.3 dimethyl

page_text: 5 pyrazolone is extracted with chloroform. Crystallised from water it melts
at 221° C.; it is easily soluble in water or chloroform, with difficulty in benzene.
6. 1 p-amidophenyl 2.3 dimethyl 5 pyrazolone. This compound is obtained from
1 p-acetylamido phenyl 2.3 dimethyl-pyrazolone by hydrolysis, which may be
carried out with concentrated hydrochloric acid. It is heated with large quantities
of concentrated hydrochloric acid on the water bath, made alkaline and shaken
with chloroform. The p-amidophenyl 2.3 dimethyl 5 pyrazolone is very easily
soluble in water, alcohol and chloroform, but only with difficulty in benzene; it.
melts at 210° C.
It differs from the very similar acetyl compound by its behaviour towards.
nitrous acid, with which it does not, like the similar compound, give a green nitroso
compound.
III. DERIVATIVES OF P-AMIDOPHENYL 2.3 DIMETHYL 5 PYRAZOLONE.
1. 1 p-dimethylamidophenyl 2.3 dimethyl 5 pyrazolone.-This compound is.
obtained by the action of methyl iodide and methyl alcohol upon the before.
mentioned compounds: 1 p-acetyl amidophenyl 3 methylpyrazolone, acetyl ether
of 1 p-acetamido phenyl 3 methyl pyrazolone, 1 p-amido-phenyl 3 methyl.
pyrazolone and 1 p-amidophenyl 2.3 dimethyl pyrazolone.
The best result is attained by heating 5 parts by weight of the latter compound
with 3-5 parts by weight of methyl iodide and 5 parts by weight of methyl alcohol.
on a boiling water bath in a closed vessel.
The 1-dimethyl amido phenyl 2.3 dimethyl 5 pyrazolone is separated from the
product of the reaction after evaporating the methyl alcohol by addition of soda.
lye and shaking with benzene.
The compound is purified by repeated crystallisation from ligroïne and ethyl
acetate and is obtained in form of lamine which melt at 134° to 135° C.
2. Benzoyl derivative of 1 p-amidophenyl 2.3 dimethyl-pyrazolone.-This.
compound is obtained as described in Example 2 of Head 1; it melts at 255° C.
3. Urethane of the same amine is obtained like the corresponding derivative of
the isomeric base, as already mentioned in Example 3 of Head I; it melts.
at 196° C.
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 herein described manufacture of new derivatives of the alphyl 2 alkyl
3 methyl 4 amidopyrazolones by alkylating and alkoylating the amido group.
2. The herein described manufacture of 1 p-amido-phenyl 2.3 dimethyl
5 pyrazolone by condensing acetyl-p-amidophenyl-hydrazine with ethylic aceto
acetate in equal molecular proportions and by either methylating and hydrolysing
the products thus obtained or by previously transforming them into such derivatives
as contain a radicle linked with oxygen and then methylating and hydrolysing the
latter.
3. The herein described manufacture of derivatives of 1 p-amidophenyl
2.3 dimethyl 5 pyrazolone by alkylating and alkoylating the amido group of this.
pyrazolone.
4. The new compounds produced as above set forth.
ABEL & IMRAY,
Agents for the Applicant.