The Manufacture of Isomeric Unsymmetrical Acetonalkamines, and Acidyl Derivatives therefrom.
Year: 1896

page_text: Date of Application, 24th Nov., 1896
Complete Specification Left, 24th Aug., 1897- Accepted, 16th Oct., 1897
ΤΟΥ
The Manufacture of Isomeric Unsymmetrical Acetonalkamines, and
Acidyl Derivatives therefrom.
I, AUGUST ZIMMERMANN, of 9 and 10 St. Mary-at-Hill in the City of London,
Merchant, do hereby declare the nature of this invention (which has been
communicated to me from abroad by The Chemische Fabrik auf Actien vormals
E. Schering of 170 and 171 Müllerstrasse, Berlin in the Empire of Germany) to be
as follows:
This invention is based upon the observation that the unsymmetrical bases of the
acetonalkamine group for example the vinyldiacetonalkamine exists in two isomeric
forms, and that as in Tropin and Tropin, the unstable form can be transformed
into the stable modification by means for example of sodium amylate.
By reducing the unsymmetrical bases of the triacetonamine group two isomeric
forms are produced one of which forms stable, the other unstable modifications. For
example on reducing vinyldiacetonamine, there is produced a vinyldiacetonalkamine
hitherto unknown which melts at 161-162° C. (unstable form) as well as that
obtained by Fischer which melts at about 121-122° (Berichte der Deutschen Chem.
Gesellschaft XVII 1794) which however as stated in the Provisional Specification
20697 of the 18th September 1896 may be transformed by crystallisation of the
hydrochloric acid salt into an unknown base melting at 138° which may be regarded
as the stable vinyldiacetonalkamine. This stable modification may also be obtained
by treating the base melting at 161-162° or by treating Fischer's body which melts
at 121-122° with sodium amylate.
J
alonly aplain this
I. PRODUCTION OF THE ISOMERIC VINYLDIACETONALKAMINE MELTING AT 161-162°
BY REDUCING VINYLDIACETONAMINE.
a) In acid solution
50 grams of vinyldiacetonamnine are dissolved in 500 grams of water and gradually
mixed with 1 kilogram of sodium amalgam. The reduction liquor is kept slightly
acid by addition of dilute sulphuric acid and is kept also at a temperature of
about 35-40°.
When all has been added, it is made alkaline, and the product of reduction
extracted with about 1 kilogram of warm water, if necessary under pressure. The
ether is afterwards distilled off to one half and the solution then left to crystallize.
Needles then crystallize out, which crystallized out of benzol melt at 162º. A body
is found in the ethereal filtrate which after crystallizing out of benzol melts at
about 121-122°.
b) Reduction in neutral solution.
50 grams of vinyldiacetonamine are dissolved in 1 kilogram of ether and reduced
with 250 grams of aluminium amalgam without cooling, a little water being gradually

page_text: added. After completion of the reduction, it is filtered and the ethereal solution
further treated as before.
II. REARRANGEMENT OF THE VINYLDIACETONALKAMINE MELTING AT 161-162° AND
OF THE BODY MELTING AT 121-122°.
This rearrangement may be brought about with sodium amylate in a similar way to
that given by Willstätter for the rearrangement of tropine into -tropine.
Example.-200 grams of amylalcohol and 20 grams of sodium are added to
20 grams of vinyldiacetonalkamine melting at 161-162° and boiled for about
twenty hours. After mixing the product of reaction with dilute hydrochloric acid
and shaking the hydrochloric acid solution with ether, an isomeric vinyldiaceton-
alkamine is precipitated out of the solution by means of potash. The isomeric
vinyldiacetonalkamine melts after recrystallizing out of henzol at 137-138°.
In the same way from the body melting at 121-122° a base melting at 137-138°
is obtained by treating with sodium amylate; this base is identical with the base
obtained from the vinyldiacetonamine melting at 161-162°.
The before described conditions are also observed in the higher homologues of
vinyldiacetonamine or alkamine for example in valeryl, oenanth, benzylidene
diacetonalkamine and generally in the homologues of analogously produced cyclical
aceton bases, which contain other aliphatic or aromatic radicals joined to
a-asymmetrical carbon or the asymmetrical cyclical aceton bases produced from the
asymmetrical phorones by treatment with ammonia.
Thus for example two isomeric forms are obtained by reducing benzylidene
diacetonamine. One form has not up to the present been obtained in a crystalline
form; the other melts at about 80°.
Example:-50 grams benzylidene diacetonamine are dissolved in dilute
hydrochloric acid and gradually mixed with about 1 kilogram of 2% sodium
amalgam. The reduction liquid is constantly kept slightly acid by addition of dilute
hydrochloric acid. When the reduction is complete, a salt separates out upon long
standing. If this be decomposed by caustic soda solution benzylidenediacetonalkamine
melting at about 80° after crystallizing out of petroleum ether, is obtained. The
salt of an oily base, which has not at present been crystallized, is obtained from the
filtrate of the difficultly soluble salt.
By treatment with sodium amylate a base is obtained, the properties of which are
not well known.
If valeryldiacetonamine is reduced at 0° in acid solution, a mixture of bases is
obtained, which have not been completely separated; the same is however
transformed by treatment with sodium amylate into a valeryldiacetonalkamine
melting at 83-85°.
From these isomeric alkamine bases or their n-alkyl derivatives, valuable alkaloids
are obtained by substituting the hydrogen atom in hydroxyle with acid radicals for
example with the benzoyl, toluyl, phenylacet, cinnamyl groups or with the mandelic
acid or tropic acid radical and the like.
I. ALKALOIDS FROM THE STABLE MODIFICATIONS OF THE UNSYMMETRICAL ALKAMINE
BASES.
If the hydrogen atom of hydroxyle in vinyldiacetonalkamine melting at 138° is
replaced with the benzoyl group, the body melting at 78° which has already been
described in the Provisional Specification 20697 of the 18th November 1896 is
obtained. The n-methyl product is obtained from this benzoylvinyldiacetonalkamine
by methylation. It may also of course be obtained by the action of benzoyl chloride
or benzoic anhydride upon the oily n-methylvinyldiacetonalkamine produced by
methylation of the base melting at 138°. The benzoyl-n-methylvinyldiacetonalkamine
is a thickly liquid oil, which has as yet not been crystallized.

page_text: In the same way as in the benzoyl compound, the other acidyl derivatives of the
vinyldiacetonamine which melts at 138°, may be obtained, as for example the toluyl
derivative, the phenylacet, cinnamyl derivative and the like by the action of the
corresponding acid chloride or anhydride upon the hydrochloric acid salt of the base
melting at 138° or upon the free base itself.
Example. Production of the p-toluyl derivative.
Molecular quantities of the dry hydrochloric acid salt of the base melting at 138°
and p-toluylchloride are heated for a few hours at about 130°. When no more.
hydrochloric acid is evolved, the product of reaction is dissolved in water, and the
solution shaken with ether to eliminate the excess of toluylchloride. The p-toluyl
derivative is then set free from the hydrochloric acid solution by means of caustic soda
solution and shaken with ether. After crystallizing out of petroleum ether, the
p-toluyl derivative is obtained in compact crystals shining like glass which melt at
about 49°.
The o-toluyl derivative which melts at about 51° is obtained in the same way.
In an analogous manner the phenylacet and cinnamyl derivative of the base
melting at 138° is obtained. The phenylacetvinyldiacetonalkamine is not
obtainable in a crystalline form. In order to purify it the crude product is washed
somewhat in hot water to eliminate small quantities of unaltered vinyldiacetonalkamine
taken up by the ether, the ethereal solution dried with potash and precipitated as a
hydrochloric acid salt by the addition of ethereal hydrochloric acid. It is a micro
crystalline powder, very easily soluble in water.
The cinnamyl derivative is an oil at present uncrystallized. The hydrochloric acid
salt is obtained in the manner before described.
In a similar way to the acidyl derivatives of the base melting at 1380, the acidyl
derivatives of the other analogously constituted unsymmetrical acetonalkamines of
the stable modifications are obtained.
Example. Production of benzoyl-valeryl-diacetonalkamine.
The ethereal solution of the valeryl-diacetonalkamine which melts at 83-85° is
transformed into its hydrochloric acid salt and the salt dried at 100° is heated with
benzoyl chloride to about 130°. The melt is then dissolved in much water and
shaken with ether to eliminate the unaltered benzoyl chloride.
The watery liquor is then made alkaline and shaken with ether. The oil remaining
behind behind crystallizes out of petroleum ether in shining needles, which melt
at 65-66°. The hydrochloric acid salt is fairly difficultly soluble in water, and
crystallizes therefrom in compact crystals shining like glass.
The benzoyl derivative from the ceranthdiacetonalkamine, not hitherto obtained in
a crystalline form is produced in an analogous way, also that of the stable benzyli-
denediacetonalkamine.
In the saine way the toluyl, phenylacet, and cinnamyl derivatives are obtained by
the application of the corresponding acid chlorides or anhydrides. The acidyl
derrivatives of the stable alkamine bases possess anæsthetic actions.
II. ALKALOIDS FROM THE UNSTABLE MODIFICATIONS OF THE UNSYMMETRICAL ACETON
ALKAMINE BASES.
If the hydrogen atom of hydroxyle in the unstable forms of the unsymmetrical
alkamines or their n-alkyl derivatives be replaced with suitable acid radicals, as for
example with the phenylglycolyl residue (mandelic acid residue) tropic acid, benzoyl,
phenylacet residue, valuable alkaloids having mydriatic action are also obtained.
1
EXAMPLES.
ALKAMINE FROM THE
UNSTABLE
PHENYLGLYCOLYL-N-METHYLVINYLDIACETON

page_text: salt of
produced in the following manner: molecular quantities of vinyldiacetonalkamine and
methyliodide dissolved in 40% methyl alcohol are allowed to stand at the temperature
of the atmosphere for about 48 hours. After that time a mixture of the iodic acid
n-methylvinyldiacetonalkamine, unaltered vinyldiacetonalkamine and
n-methylvinyldiacetonalkamine iodmethytate separate out. The mixture is evaporated
to dryness, taken up with water, supersaturated with potash, and shaken out several
times with ether whereby the undissolved ammonium compound remains behind
undissolved. After evaporation of the ethereal solution it is boiled several times with
petroleum ether. The unaltered vinyldiacetonalkaminealkamine thereby remains
behind unaltered. The n-methylvinyldiacetonalkamine crystallizes out of the
petroleum ether on cooling in silk glossy needles melting at 84-85°.
To produce the phenylglycolyl derivative, Ladenburg's method is the best to
follow: A thin solution of the n-methylated base displaced an with excess of mandelic
acid, is several times evaporated with small quantities of hydrochloric acid. The
residuum is taken up with water, mixed with a few drops of hydrochloric acid and
shaken several times with ether. The acid solution is then supersaturated in the
cold with soda solution, shaken out with ether, whereupon the ether residuum is
washed with water. The oil remaining behind after the evaporation of the ether
gradually solidifies to a crystalline mass, which is washed with cold petroleum ether, in
which the alkaloid is difficultly soluble. It crystallizes out of hot petroleum ether in
pupils melting at 112-113°. The hydrochloric acid salt is extraordinarily deliquescent;
it possesses a strong mydriatic action in a 2% solution.
The mandelic acid derivative may also, but little advantageously be obtained by
treating the vinyldiacetonalkamine melting at 161-162° with mandelic acid according
to Ladenburg's method and methylating the phenylglycolyl-vinyldiaceton alkamine
produced thereby in small quantities with methyliodide.
The phenylglycolyl derivatives may also be produced by the action of mandelic
anhydride in place of mandelic acid.
2. TROPYL-N-METHYL-VINYLDIACETONALKAMINE
FROM THE BASE MELTING
AT 161°-162°.
Proceed exactly as before, by repeatedly evaporating upon the water bath the
solution in water of the n-methylated vinyldiacetonalkamine melting at 161-162°
mixed with tropic acid hydrochloric acid being added from time to time.
The further working is carried out as under 1. After washing the crude product
with water, tropyl-n-methyl-vinyldiacetonalkamine remains behind as a quickly
solidifying oil. The base is very difficultly soluble in water; it is easily saponified by
a boiling soda solution. The hydrochloric acid salt is very diliquescent. It possesses
very strong mydriatic action very similar to the hydrochloric acid salt of the
corresponding mandelic acid derivative.
3. BENZOYL DERIVATIVE OF
VINYLDIACETONALKAMINE
MELTING AT 161-162° AND
THE N-METHYLATION OF THE SAME.
a) Benzoyl-vinyldiacetonalkamine.
The ethereal solution of the base melting at 161-162° is first transformed into
the hydrochloric acid salt. This is heated for a long time with molecular quantities
of benzoyl chloride to about 140°, the product of reaction is placed in water and
3. BENZOYL DERIVATIVE OF VINYLDIACETONALKAMINE MELTING AT 161-162° AND
THE N-METHYLATION OF THE SAME.
a) Benzoyl-vinyldiacetonalkamine.
The ethereal solution of the base melting at 161-162° is first transformed into
the hydrochloric acid salt. This is heated for a long time with molecular quantities
of benzoyl chloride to about 140°, the product of reaction is placed in water and
shaken with ether to eliminate the excess of benzoyl chloride. The solution in water 4
is then supersaturated with soda and again shaken out with ether. After distillation
of the ether, benzoyl-vinyldiacetonalkamine remains behind as an uncrystallizable
oil. The hydrochloric acid salt is obtained in a micro crystalline state by mixing an
ethereal solution of the base with ethereal hydrochloric acid. It possesses mydriatic
and anæsthic properties.
3) Renzovl.n.methyl-vinyldiacetonalkamine
5

page_text: The n-methyl product is obtained either by the action of methyl iodide upon the
unmethylated base obtained as under a, by heating molecular quantities in
methylalcoholic solution with methyl iodide, or by benzoylating n-methyl-
vinyldiacetonalkamine. The resulting base is an oil. The hydrochloric acid salt
possesses mydriatic and anæsthetic properties.
The phenylacet derivative of vinyldiacetonalkamine and n-methyl-vinyldiaceton-
alkamine also form oils.
In the same way as the vinyldiacetonalkamine melting at 161-162° the unstable
forms of benzylidene diacetonalkamine, valeryl diacetonalkamine and analogous
unsymmetrical alkamine bases are transformed into acidyl derivatives.
Dated this 24th day of November 1896.
AUGUST ZIMMERMANN.
The Manufacture of Isomeric Unsymmetrical Acetonalkamines and
Acidyl Derivatives therefrom.
I, AUGUST ZIMMERMANN, of 9 and 10 St. Mary-at-Hill, in the City of London,
Merchant, do hereby declare the nature of this invention, (which has been
communicated to me from abroad by The Chemische Fabrik auf Actien vorinals
E. Schering of 170 and 171 Müllerstrasse, Berlin, in the Empire of Germany) and
in what manner the same is to be performed to be particularly described and
ascertained in and by the following statement:-
This invention is based upon the observation that the unsymmetrical bases of the
acetonalkamine series for example the vinyldiacetonalkamine exists in two isomeric
forms, and that as in Tropin and Tropin, the unstable form can be transformed
into the stable modification by means for example of sodium amylate.
By reducing the unsymmetrical bases of the triacetonamine group two isomeric
forms are produced, one of which represents the stable, the other the unstable
modification. For example on reducing vinyldiacetonamnine, there is produced a
vinyldiacetonalkamine hitherto unknown which melts at 161-162° C. (unstable
form) as well as that obtained by Fischer which melts at about 121-122° (Berichte
der Deutschen Chem. Gesellschaft XVII 1794) which, however, as stated in the
Provisional Specification 20697 of the 18th September 1896, may be transformed by
crystallisation of the hydrochloric acid salt into an unknown base melting at 138°
which may he regarded as the stable vinyldiacetonalkamine. This stable modification
may also be obtained by treating the base melting at 161-162° or by treating
Fischer's body which melts at 121-122° with sodium amylate or other alkylate.
The following examples more clearly explain this:-
(I) PRODUCTION AND SEPARATION OF THE ISOMERIC VINYLDIACETONALKAMINES.
a) In acid solution.
50 grams of vinyldiacetonamine are dissolved in 500 grams of water and gradually
mixed with 1 kilogram of sodium amalgam. The reduction liquor is kept slightly
acid by addition of dilute sulphuric acid and is kept also at a temperature of
about 35-40°.
When all has been added, it is made alkaline and the product of reduction
extracted with about 1 kilogram of warm ether, if necessary under pressure. The
ether is afterwards distilled off to one half and the solution then left to crystallize.
Needles then crystallize out, which crystallized out of benzol, melt at 161-162°.

page_text: A body is found in the ethereal filtrate which after crystallizing out of benzol
melts at about 121-122°, and appears to be a uniform combination of the
alkamine melting at 161-162° and the true stable modification.
b) Reduction in neutral solution.
50 grams of vinyldiacetonamine are dissolved in 1 kilogram of ether and reduced
with 250 grams of aluminium amalgam without cooling, a little water being gradually
added. After completion of the reduction it is filtered, and the bases are separated
by crystallization as stated before.
(II) TRANSFORMATION OF THE VINYLDIACETONALKAMINE MELTING AT 161-162°
OF THE BODY MELTING AT 121 122° INTO THE STABLE MODIFICATION
MELTING AT 1389.
AND
This transformation may be brought about with for instance sodium amylate
in a similar way to that given by Willstätter for the transformation of tropine into
tropine.
Example.-200 grams of amyl-alcohol and 20 grams of sodium are added to
20 grams of vinyldiacetonalkamine melting at 161-162° and boi'ed for about
twenty hours. After mixing the product of reaction with dilute hydrochloric acid
and shaking the hydrochloric acid solution with ether, an isomeric vinyldiaceton-
alkamine is precipitated out of the solution by means of potash. The isomeric
vinyldiacetonalkamine melts after recrystallizing out of benzol at 137-138°.
In the same way from the body melting at 121-122° a base melting at 137-138°
is obtained by treating with sodium amylate; this base is identical with the base
obtained from the vinyldiacetonamine melting at 161-162°.
The before described conditions are also observed in the higher homologues of
vinyldiacetonamine or alkamine, for example in valeryl, oenanth-piperonylene-
benzylidene diacetonalkamine and generally in the homologues of analogously
produced cyclical aceton bases, which contain other aliphatic or aromatic adicals
joined to a-asymmetrical carbon or the asymmetrical cyclical aceton bases produced
from the asymmetrical phorones by treatinent with ammonia.
Thus for example are obtained-:
1. Two ISOMERIC VALERYLDIACETONALKALMINES BY THE REDUCTION OF VALERYL-
DIACETONAMINE.
Example.-50 grams valeryldiacetonamine are dissolved in 50 grams of water and
gradually mixed with about 1 kilogram of 2% sodium amalgam. The reduction
liquor is constantly kept slightly acid by addition of dilute sulphuric acid and its
temperature at about 35-40°. The product of reduction is made alkaline, shaken
with ether, and the ethereal solution dried with potash and evaporated. The
separation of the bases is here preferably performed by crystallization out of
petroleum ether. To the residum is added twice its weight of petroleum ether
and is kept cool.
After some time the unstable valeryldiacetonalkamine crystallizes out, which after
repeated recrystallizations melts at 93-94°. The stable modification of the alkamine
is contained in the filtrate, and in a pure state has a melting point of 80--82°.
2. BENZYLIDENE DIACETONALKAMINES.
By reducing benzylidene diacetonamine in the manner above described, two
isomeric benzylidene diacetonalkamines are also obtained. On long standing after
reduction is complete a salt separates out. If this be mixed with caustic soda
solution, a base is obtained which after recrystallization out of petroleum ether
melts at about 68° and must be looked upon as the unstable modification.
In the

page_text: 3. PIPERONYLENEDIACETONALKAMINES.
If piperonylenediacetonamnine be reduced in the manner above describe an
alkamine is obtained by crystallization out of petroleum ether which represents
the unstable form and possesses a melting point of 108—109°. The stable
modification is found in the filtrate.
The stable forms of the alkamines mentioned under 1, 2 and 3 may also be
obtained in the manner described for the stable form of vinyldiacetonalkamine viz.
by treating the corresponding unstable modifications or from the mixture of both
alkamines obtained by reduction of the acetonamine bases in question with sodium
alkylates.
From these isomeric alkamine bases or their n-alkyl derivatives valuable alkaloids
are obtained by replacing the hydrogen atom in hydroxyle by acid radicals for
example with the benzoyl, toluyl, phenylacet, cinnamyl groups or with the mandelic
acid or tropic acid radical and the like.
(I) ALKALOIDS FROM THE STABLE MODIFICATIONS OF THE UNSYMMETRICAL ACETON-
ALKAMINE BASES.
If the hydrogen atom of hydroxyle in vinyldiacetonalkamine melting at 138° is
replaced with the benzoyl group, the body melting at 78° which has already been
described in the Provisional Specification 20697 of the 18th November 1896 is
obtained. The n-methyl product is obtained from this benzoylvinyldiacetonalkamine
by methylation. It may also of course be obtained by the action of benzoyl chloride
or benzoic anhydride upon the oily n-methylvinyldiacetonalkamine produced by
methylation of the base melting at 138. The benzoyl-n-methylvinyldiaceton-
alkamine is a thickly liquid oil, which has as yet not been crystallized.
In the same way as in the benzoyl compound, the other acidyl derivatives of the
vinyldiacetonamine which melts at 138°, may be obtained, as for example, the
toluyl derivative, the phenylacet, cinnamyl derivative and the like by the action of
the corresponding acid chloride or anhydride upon the hydrochloric acid salt of the
base melting at 138° or upon the free base itself.
Example. Production of the p-toluyl derivative.
Molecular quantities of the dry hydrochloric acid salt of the base melting at 138°
and p-toluylchloride are heated for a few hours at about 130°. When no more
hydrochloric acid is evolved, the product of reaction is dissolved in water, and the
solution shaken with ether to eliminate the excess of toluylchloride. The p-toluyl
derivative is then set free from the hydrochloric acid solution by means of caustic
soda solution and shaken with ether. After crystallizing out of petroleum ether,
the p-toluyl derivative is obtained in compact crystals shining like glass which melt
at about 49°.
The o-toluyl derivative which melts at about 51° is obtained in the same way.
In an analogous manner the phenylacet and cinnamyl derivative of the base
melting at 1380 is obtained. The phenylacetvinyldiacetonalkamine is not obtainable
in a crystalline form. In order to purify it the crude product is washed somewhat
in hot water to eliminate small quantities of unaltered vinyldiacetonalkamine taken
up by the other, the ethereal solution dried with potash and precipitated as
hydrochloric acid salt by the addition of ethereal hydrochloric acid. It is a micro-
crystalline powder, very easily soluble in water.
a
The cinnamyl derivative is an oil at present uncrystallized. The hydrochloric
acid salt is obtained in the manner before described.
In a similar way to the acidyl derivatives of the base melting at 138°, the acidyl

page_text: 1. PHENYLGLYCOLYL-N-METHYLVINYLDIACETONALKAMINE FROM THE UNSTABLE
VINYLDIACETONALKAMINE MELTING AT 161-162°.
The n-methylvinyldiacetonalkamine necessary for the purpose is preferably
produced in the following manner: Molecular quantities of vinyldiacetonalkamine
and methyliodide dissolved in 40 % methyl alcohol are allowed to stand at the
temperature of the atmosphere for about 48 hours. After that time a mixture of
the iodic acid salt of n-methylvinyldiacetonalkamine, unaltered vinyldiaceton-
alkamine and n-methylvinyldiacetonal kamine, iodmethylate separate out. The
inixture is evaporated to dryness, taken up with water, supersaturated with
potash and shaken out several times with ether whereby the undissolved ammonium
compound remains behind undissolved. After evaporation of the ethereal solution
it is boiled several times with petroleum ether. The unaltered vinyldiaceton-
alkamine thereby remains behind unaltered. The n-methylvinyldiacetonalkamine
crystallizes out of the petroleum ether on cooling in silk glossy needles melting
at 84-85°.
To produce the phenylglycolyl derivative, Ladenburg's method is the best to
follow: A thin solution of the n-methylated base to which an excess of mandelic
acid is added is several times evaporated with small quantities of hydrochloric acid.
The residuum is taken up with water, mixed with a few drops of hydrochloric acid
and shaken several times with ether. The acid solution is then supersaturated in
the cold with soda solution, shaken out with ether, whereupon the ether residuum
is washed with water. The oil remaining behind after the evaporation of the ether
gradually solidifies to a crystalline mass, which is washed with cold petroleum ether,
in which the alkaloid is difficultly soluble. It crystallizes out of hot petroleum
ether in pupils melting at 112-113°. The hydrochloric acid salt is extraordinarily
deliquescent; it possesses a strong mydriatic action in a 2 % solution.
The mandelic acid derivative may also, but little advantageously be obtained by
treating the vinyldiacetonalkamine melting at 161-1620 with mandelic acid

page_text: according to Ladenburg's method and methylating the phenylglycolyl-vinyldiaceton-
alkamine produced thereby in strall quantities with methyliodide.
The phenylglycolyl derivatives may also he produced by the action of mandelic
anhydride in place of mandelic acid.
2. PHENYLGLYCOLYL-N-ETHYL-VINYLDIACETONALKAMINE FROM THE UNSTABLE
VINYLDIACETONALKAMINE.
The n-ethylvinyldiacetonalkamine required therefor is produced in exactly the
same way as the corresponding methyl product and forms an oil. The
phenylglycolyl derivative obtained therefrom is a micro crystalline powder melting
at 88-91°. The base is insoluble in water as is the corresponding alkaloid from
n-methylvinyldiacetonalkamine, but easily soluble in alcohol and ether; the salts
are very easily soluble in water and possess strong mydriatic action.
3. PHENYLGLYCOLYL-VINYLDIACETONALKAMINE.
The product of reaction obtained by Ladenburg's method is mixed with soda
solution, repeatedly shaken with ether, the ethereal solution dried with potash,
evaporated, and the product treated with cold water. The greater portion of
unstable vinyldiacetonalkamine not reacted upon is thereby dissolved, whilst the
phenylglycolyl alkaloid remains behind undissolved. It has a melting point of
150-177°. It has hitherto not been obtained in a pure state; it contains however
inandelic acid in a great measure combined, which after saponification of the
alkaloid is easily demonstrated. The salts of the base possess weak, but recognisable
mydriatic action.

page_text: methylalcoholic solution with methyl iodide, or by benzoylating-n-methyl-vinyldiace-
tonalkamine. The resulting base is an oil. The hydrochloric acid salt possesses
mydriatic and anesthetic properties.
7. PHENYLACET-VINYLDIACKTONALKAMINE.
Phenylacet-vinyldiacetonalkamine is obtained by the reaction of phenylacetic acid
chloride upon the unstable alkamine and also forms an oil. It splits up by boiling
with caustic soda solution into phenylacetic acid and vinyldiacetonalkamine melting
at 161-162°. The salts are easily soluble in water and possess weak mydriatic and
strong anæsthetic action.
In the same way as the unstable vinyldiacetonalkamine the unstable modifications
of analogously constituted unsymmetrical acetonalkamines such as for example the
valeryl, piperonylene, benzylidene and oenanth diacetonalkamines may be transformed
into acidyl derivatives.
Phenylacet-vinyldiacetonalkamine is obtained by the reaction of phenylacetic acid
chloride upon the unstable alkamine and also forms an oil. It splits up by boiling
with caustic soda solution into phenylacetic acid and vinyldiacetonalkamine melting
at 161-162°. The salts are easily soluble in water and possess weak mydriatic and
strong anæsthetic action.
In the same way as the unstable vinyldiacetonalkamine the unstable modifications
of analogously constituted unsymmetrical acetonalkanines such as for example the
valeryl, piperonylene, benzylidene and oenanth diacetonalkamines may be transformed
into acidyl derivatives.
The n-methyl derivative of the unstable enanthdiacetonalkamine melting
at 77-79° C. is an oil, as is also the mandelic derivative obtained therefrom which
possesses recognizable mydriatic action.
12. PHENYLGLYCOLYL-N-METHYL-PIPBRONYLDIACETONALKAMINE.
The n-methylpiperonylenediaceton alkamine required therefor is produced from the
unstable piperonylenediaceton alkamine (melting point 108-109°) and crystallizes
out of benzol in satin shining leaves having a melting point of 152-153°. The
mandelic derivative remains after distilling off the ether as a crystalline mass, out of
hot petroleum ether it is a crystalline powder melting at about 150°. It possesses
mydriatic properties.
Having now particularly described and ascertained the nature of ny said
invention and in what manner the same is to be performed I wish it to be under-

page_text: stood that I do not claim under this application vinyldiacetonalkamine melting
at 138° C. and its derivatives as new products or the special method of production of
local anaesthetics from the vinyldiacetonalkamine melting at 138° which form the
subject matter of the Patent No. 20697 of 1896 but that subject to the above disclaimer
what I claim is :-
1. The production of isomeric unsymmetrical cyclical bases of the acetoalkamine
series by separating by crystallization the mixture of unstable and stable
alkamines obtained by reduction of the unsymmetrical cyclical acetonamine bases.
2. The production of the stable unsymmetrical cyclical bases of the acetonalkamine
series consisting in treating the unstable acetonalkamines or the mixture of isomeric
alkamines obtained by reduction of the unsymmetrical acetonamine bases with
alkylates.
3. The production of acidyl derivatives of the stable and unstable modifications of
unsymmetrical cyclical acetonamine bases and of their n-alkyl derivatives consisting
in replacing the hydrogen atom of hydroxyle in these compounds by suitable acid
radicals (such as the benzoyl toluyl, phenylacetyl, mandelic acid, tropic acid radical).
4. As new isolated chemical products the herein described stable and unstable
modifications of the unsymmetrical cyclical acetonalkamine bases.
5. As new chemical products the herein described acidyl compounds of the unstable
and stable forms of the unsymmetrical cyclical acetonalkamine bases and of their
n-alkyl derivatives.
Dated this 10th day of Aunt 1007