Aldehydes.
Year: 1886

page_text: Date of Application, 27th May, 1886.
Complete Left, 26th Feb., 1887.
Complete Accepted, 29th Mar., 1887.
RESERVE
[Communicated from abroad by the FARBWERKE VORMALS MEISTER LUCIUS AND
BRUNING, of Hoechst-am-Main, in the Empire of Germany, a Company carrying
on business as Chemical Manufacturers.]
Aldehydes.
I, CHARLES DENTON ABEL, of No. 28 Southampton Buildings, Chancery Lane
in the County of Middlesex, Consulting Engineer and Patont Agent, do hereby
declare the nature of this invention to be as follows:-
:-
The compounds of the secondary aromatic hydrazines with the pyroracemic acid
heated with hydrochloric acid part with the elements of ammonia and are converted
into the carbonic acids of the alkylised indols (Berichte d. Deutschen chem."
Gesellschaft XVII, 559).
In this way the metliylindol-carbonic acid has been prepared from the methyl-
phenylhydrazine pyroracemic acid.
From the experiments made it appeared however that the reactions were confined
to the secondary bydrazines and the pyroracemic acid, as from the compound of the
primary phenylhydrazine with the same ketonic acid no indol-derivative is obtained' in
this way. This applies also to the compounds of the hydrazines with the ordinary
ketones which by means of the aqueous mineral acids are not converted into indol-
derivatives but are decomposed into their components.
By using other ammonia-removing agents my correspondents have succeeded in
developing that isolated fact into a general synthesis of indol-derivatives.
As is well known, all the aromatic hydrazines, primary and secondary, react with
ketones and aldehydes, parting with water.
As examples, may serve the following cases, viz.
1. Phenylhydrazine + acetone
=
C₁ H.N, H, + CH..CO.CH
2, Methylphenylhydrazine + acetone
C. H. N (CH,).NH, +CH, CO. CH.
3, Phenylhydrazine propylaldehyde
ŻOH ( H
CHN H.
=
=
Acetonephenylhydrazine + water
C, HN, H C (CH₁), + H₂O
Acetonemethylphenylhydrazine + water
C. HN (CH) N.C (CH).
Propylidenephenylhydrazine + water
C HN F. CH. C. H.
+H₂
+H.O
0

page_text: If these products are treated in a suitable maner such as hereafter described with
anhydrous acids or preferably with metallic chlorides, such as chloride of zinc or
stannous chloride, they part with the elements of ammonia and are converted into
indol derivatives. For the above three cases the reaction is represented by the
following equations :
the above examples.
1. If acetonephenylhydrazine is dissolved in concentrated sulphuric acid heated for
a short time on a water bath and diluted with water small quantities of methylketol
will be obtained by distillation with steam.
The yield will be somewhat larger if anhydrous hydrochloric acid is allowed to flow
into acetonephenylhydrazine, whereupon the oil solidifies owing to the formation of a
hydrochlorate. If now this product is heated to 200° C there will be produced
methylketol in variable quantities.
The process will occur very much more smoothly when zinc chloride is employed.
If the acetonephenylhydrazine is mixed with from 4 to 5 times its quantity of
solid zinc-chloride and heated on a bath of 170 to 180° C., the reaction will set in
after from 1 to 2 minutes and it will be finished in a few minutes, the mass melting
and taking a dark color. If, after having cooled down, the mass, in order to dissolve
the zinc chloride, is treated with water and then distilled with steam, the methylketol
passes into the recipient in form of a nearly colorless oil solidifying promptly. The
product has all the characteristic properties mentioned by Baeyer and Jackson for the
methylketol prepared by these chemists in another way (Berichte d. Deutsch. chem.
Ges. XIII 187). The yield is above 60 per cent. of the theoretical amount.
If acetonephenylhydrazine is heated with dry tin-chloride an analogous result will
be obtained.
2. When the acetonemethylphenylhydrazine is heated for several hours to 130° C
with the quintuple quantity of zinc chloride a dark melt will result from which by
distillation in steam is obtained very easily and in large quantity dimethylindol
ATT

page_text: these phenomena set in. From the dark melt is obtained by distillation in steam a
large quantity of skatole, which is obtained in a chemically pure state by a single
recrystallisation from ligroin.
The same reaction takes place, but less smoothly when tin chloride is used.
The formation of indols from the compounds of the hydrazines with the aromatic
ketones occurs in quite the same manner, as described before. For instance:
1, From the acetophenonephenylhydrazine heated to 170° C with chloride of zinc
is formed
quito smoothly the phenylindol CH
CH
NH/
C. CH, which in rarefied air distills
off undecomposed and crystallines in fine colorless and inodorous leaflets melting
at 185° C.
2, The acetophenone-methylphenylhydrazine treated in the same way yields the
is obtained, which also distils undecomposed and has the melting point 123° C.
In place of the phenyl- and methyl-phenyl-hydrazine may be used with the same
result in the above reaction their halogen-substitution products and homologues,
like the various tolyl- and xylylhydrazines, further the hydrazine of the benzidine, the
hydrazine sulphonic acids and the hydrazine benzoic acids or their alkyl-derivatives.
Even in the series of naphthalines the conditions are the same.
When, for instance, the acetone-beta-naphthylhydrazine (which is formed quite
easily by dissolution of beta naphthyl-hydrazine in acetone and remains in form of an
oil solidifying promptly, when the solution is evaporated) is heated for a few minutes
to 170° with zinc chloride, and afterwards treated with water, there results a dark
oil, from which by distillation in vacuum is obtained the methyl-beta-naphth-indol
CH
NH
C₁H
C. CH, in form of a slightly colored oil, which in presence of hydro-
chloric acid colors pine wood blue-violet and forms a nicely crystallised red pierate.
In place of the ordinary ketones and aldhydes can be used their carbonic acids.
For instance: When phenylhydrazinelaeveulic acid is heated for several hours to
120-130° C on an oil bath with zinc chloride, and the melt is treated with feeble
hydrochloric acid, there remains undissolved a yellow-colored mass which,
recrystallised from glacial acetic acid, yields a colorless acid of the formula
CHNO, Heated above 190° C this acid splits up into carbonic acid and the
compound C₁HN. The latter forms colorless lustrous leaflets melting at 103° C.
and from its behaviour it is to be considered as dimethylindol.
10'

page_text: In accordance with this the carbonic acid mentioned before is the methylindol-acetic
acid
The compounds of the phenylhydrazine with the pyroracemic acid and their ethers
shew an analogous behaviour.
When the phenylhydrazinepyroracemic acid is heated to 190° C with an equal
quantity of chloride of zinc, an impetuous reaction occurs, and from the dark melt
will be obtained, by distillation in steam, small quantities of indol formed by the
decomposition of an intermediary indol-carbonic acid.
When ether is employed, the action passes off more smoothly.
When the phenylhydrazinepyroracemic acid ethyl ether (Berichte d. D. ch.
Ges. XVI 2243) is heated to 190° C. for some time with an equal weight of zinc
chloride, there results a dark melt, which, treated with water, gives up to ether a
large quantity of an oil consisting in great part of indolcarbonic acid ether. Heated
with alkalis, this ether is easily saponified and on acidulation of the solution the
indolcarbonic acid separates in crystalline form. It can be easily recrystallised from
Heated above
hot water and has the formula C,H,NO,; it forms fine needles.
220° C the compound parts with carbonic acid and yields considerable quantities of
indol which by distillation in steam is obtained in a pure state. In the same way the
aceto acetic ether can be used for the indol synthesis.
The indol bodies thus obtained are intended for use in the preparation of coloring
matters and also they are to be employed as antiseptics.
ABEL & IMRAY,
28, Southampton Buildings, London, W.C.,
Agents for the Applicant.

page_text: COMPLETE SPECIFICATION.
Improvements in the Production of Indolderivatives from the
Compounds of the Aromatic Hydrazines with the Ketones and
Aldehydes.
1, CHARLES DENTON ABEL of No. 28 Southampton Buildings, Chancery Lane in
the County of Middlesex, Consulting Engineer and 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 :-
The compounds of the secondary aromatic hydrazines with the pyroracemic acid
heated with hydrochloric acid part with the elements of ammonia and are converted
into the carbonic acids of the alkylised indols (Berichte d. Deutschen chem:
Gesellschaft XVII, 559).
In this way the methylindol-carbonic acid has been prepared from the methylphenyl-
hydrazine pyroracemic acid.
From the experiments made it appeared however that the reactions were confined to
the secondary hydrazines and the pyroracemic acid, as from the compound of the
primary phenylhydrazine with the same ketonic acid no indol-derivative is obtained in
this way. This applies also to the compounds of the hydrazines with the ordinary
ketones which by means of the aqueous mineral acids are not converted into indol-
derivatives but are decomposed into their components.
By using other ammonia-removing agents my correspondents have succeeded in
developing that isolated fact into a general synthesis of indol-derivatives.
As is well known, all the aromatic hydrazines, primary and secondary, react with
ketones and aldehydes, parting with water.
As examples, may serve the following cases, viz.
1. Phenylhydrazine + acetone
C, H. N₂ H, + CH.. CO. CH
2
2. Methylphenylhydrazine + acetone
=
=
Acetonephenylhydrazine + water
C H.. N. H: C (CH,), + H, 0
Acetonemethylphenylhydrazine+water
C, H. N (CH,). NH, + CH. CO. CH, TỪ H. N (CH,) NỐC (CH,), +H, 0
3. Phenylhydrazine + propylaldehyde
CH. N₂ H₂ + COH. C₂ H,
2
=
Propylidenephenylhydrazine + water
CH. N, H. CH. C, H,
+ H₂ O.
If these products are treated in a suitable manner such as hereafter described with
anyhydrous acids or preferably with metallic chloride, such as chloride of zinc or
stannous chloride, they part with the elements of ammonia and are converted into
indol-derivatives. For the above three cases the reaction is represented by the
following equations :
1 Acetonenhenylhydrazine
Ammonia + Methylketol

page_text: the above examples.
1. If acetonephenylhydrazine is dissolved in concentrated sulphuric acid heated
for a short time on a water bath and diluted with water small quantities of methylketol
will be obtained by distillation with steam.
The yield will be somewhat larger if anhydrous hydrochloric acid is allowed to
flow into acetonephenylhydrazine, whereupon the oil solidifies owing to the formation
of a hydrochlorate. If now this product is heated to 200° C there will be produced
methylketol in variable quantities.
The process will occur very much more smoothly when zinc chloride is employed.
If the acetonephenylhydrazine is mixed with from 4 to 5 times its quantity of solid
zine-chloride and heated on a bath of 170 to 180° C, the reaction will set in after
from 1 to 2 minutes and it will be finished in a few minutes, the mass melting and
taking a dark color. If, after having cooled down, the mass, in order to dissolve the
zinc chloride is treated with water and then distilled with steam, the methylketol
passes into the recipient in form of a nearly colorless oil solidifying promptly. The
product has all the characteristic properties mentioned by Baeyer and Jackson for the
methylketol prepared by these chemists in another way (Berichte d. Deutsch, chem.
Ges. XIII. 187). The yield is above 60 per cent. of the theoretical amount. If
acetonephenylhydrazine is heated with dry tin chloride an analagous result will be
obtained.
2. When the acetonemethylphenylhydrazine is heated for several hours to 130° C
with the quintuple quantity of zinc chloride a dark melt will result from which by
distillation in steam is obtained very easily and in large quantity dimethylindol
CITT
3. When propylidenephenyldrazine is mixed with an equal quantity of zinc chloride
in powder the reaction will sometimes set in spontaneously under strong evolution of
heat and foaming of the mass, if not, it must be licated on a bath until these phenomena
.set_in. From the dark melt is obtained by distillation in steam a large quantity of
skatole which is obtained in a chemically pure state by a single recrystallisation from
ligroin. The same reaction takes place, but less smoothly when tin chloride is used.
The formation of indols from the compounds of the hydrazines with the aromatic
ketones occurs in quite the same manner, as described before. For instance.
1. From the acetophenonephenylhydrazine heated to 170° C with chloride of zinc
is formed quite smoothly the phenylindol C, H₁
NH
CC. H, which in
-

page_text: 2. The acetophenone-methylphenylhydrazine treated in the same way yields the
is obtained, which also distils undecomposed and has the melting point 123° C.
In place of the phenyl- and methylphenylhydrazine may be used with the same
result in the above reactions their halogen substitution products and homologues, like
the various tolyl and xylylhydrazines further the hydrazine of the benzidine, the
hydrazine sulphonic acids and the hydrazine benzoic acids or their alkyl-derivatives.
Even in the series of the naphthalines the conditions are the same.
When, for instance, the acetone-beta naphthylhydrazine (which is formed quite
easily by dissolution of beta-naphthylhydrazine in acetone and remains in form of an
oil solidifying promptly, when the solution is evaporated) is heated for a few minutes
to 170° C with zinc chloride, and afterwards treated with water, there results a dark
oil, from which by distillation in vacuum is obtained the methyl-beta-naphth-
indol C
✓ HKNH
C. CH, in form of a slightly colored oil, which in presence of
hydrochloric acid colors pine wood blue-violet and forms a nicely crystallised red
picrate.
In place of the ordinary ketones and aldehydes can be used their carbonic acids.
For instance : When phenylhydrazinelaevulic acid is heated for several hours
to 120-130° C on an oil bath with zinc chloride, and the melt is treated with feeble
hydrochloric acid, there remains undissolved a yellow colored mass which, recrystal-
lised from glacial acetic acid, yields a colorless acid of the formula C, H, NO..
Heated above 190° C this acid splits up into carbonic acid and the compound C H₁₁ N..
The latter forms colorless lustrous leaflets melting at 103° C, and from its behaviour it
is to be considered as dimethylindol

page_text: The compounds of the phenylhydrazine with the pyroracemic acid and their ethers
shew an analagous behaviour.
When the phenylhydrazinepyroracemic acid is heated to 190° C with an equal
quantity of chloride of zinc, an impetuous reaction occurs, and from the dark melt will
be obtained, by distillation in steam, small quantities of indol formed by the decomposi-
tion of an intermediary indol carbonic acid.
When ether is employed, the action passes off more smoothly. When the
phenylhydrazinepyroracemic acid ethyl ether (Berichte d. D. ch. Ges XVI 2243) is
heated to 190°C for some time with an equal weight of zinc chloride, there results a
dark melt, which, treated with water, gives up to ether a large quantity of an oil
consisting in great part of indolcarbonic acid ether. Heated with alkalies, this ether
is easily saponified and on acidulation of the solution the indolcarbonic acid separates
in crystalline form. It can be easily recrystallised from hot water and has the
formula C, H, NO,; it forms fine needles. Heated above 220° C the compound parts
with carbonic acid and yields considerable quantities of indol which by distillation in
steam is obtained in a pure state. In the same way the aceto acetic ether can be used
for the indol synthesis.
The indol bodies thus obtained are intended for use in the preparation of coloring
matters and also they are to be employed as antiseptics.
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:-
i
The production of indolderivatives from the compounds of the aromatic hydrazines
with the aldehydes, the ketones, the ketonic acids and their ethers by means of
ammonia-removing agents, such as acids like hydrochloric acid, concentrated sulphuric
acid or metallic chlorides like zinc chloride or stannous chloride. From among the
hydrazines can be used for this purpose: the primary and secondary aromatic bases:
phenyl-tolyl-xylyl alpha- or beta- naphthyl-hydrazine, further their sulphonic and
carbonic acids such as the hydrazine benzoic acid, also the derivatives of the bases
specified alkylised in the nitrogen radical such as methyl- or ethylphenylhydrazine
and diphenyl-hydrazine. As ketones may serve acetone and its homologues, such as
methylethylketone, diethylketone, methylpropylketone, also the aromatic ketones such
as acetophenone benzylmethylketone, desoxybenzoin. From among the aldeliydes
may be applied propylbutyl-valer-aldehyde, oenanthol, phenylacetaldehyd.
As ketonic acids may be used the pyroracemic acid or its ethers; acetoacetic ether
and laevulic acid' and its ethers..
Dated this 26th day of February 1887.
ABEL & IMRAY,
Agents for the Applicant.