The Preparation of a Crystalline Polymeric Base, suitable for Medical Use, from Amido-acetic Aldehyde.
Year: 1893

page_text: Date of Application, 15th Dec., 1893
Complete Specification Left, 17th Sept., 1894-Accepted, 20th Oct., 1894
PROVISIONAL SPECIFICATION.
The Preparation of a Crystalline Polymeric Base, suitable for
Medical Use, from Amido-acetic Aldehyde.
I, SYDNEY PITT, of Sutton, in the County of Surrey, Gentleman, (a com-
munication to me from abroad by The Chemische Fabrik auf Actieu vorm.
E. Schering, of 170 Müllerstrasse, Berlin,) do hereby declare the nature of this
invention to be as follows:-
0
As Emil Fischer has recently shown, the salts of amido-acetic aldehyde are
produced by the action of strong mineral acids on amidoacetal at ordinary
temperatures. If hydrochloric acid or hydrobromic acid is employed the salts of
these acids remain behind on evaporation in vacuum as a non-crystalline syrup.
The latter is characterised by its great solubility in water and alcohol, by its
strong reducing action on Fehling's solution and by its ready decomposition on
boiling with water or alkalies. In keeping the acid syrup for some time at ordinary
temperatures apparently only a slight change takes place, rendered visible by the
syrup browning. In reality however a part of the amido acetic aldehyde is
converted into a new crystalline base. The latter possesses the same empirical
composition as amido-acetic aldehyde, but is distinguished from it by the indifference
of the new base towards alkalies and towards Fehling's solution, as well as by the
crystallising powers and stability of its salts. Its properties indicate that it is a
polymeride of amido-acetic aldehyde.
It is most easily obtained direct from amidoacetal by employing hydrobromic
acid in the following manner. Amidoacetal is introduced into cooled hydrobromic
acid of 1.49 specific gravity as in the preparation of amido-acetic aldehyde and the
liquid after standing for five hours at the temperature of the room evaporated as
far as possible in a vacuum from a bath the temperature of which does not rise
above 60° C. The slightly yellow coloured syrup, which contains the hydro-
bromide of amido-acetic aldehyde is then allowed to stand in open vessels over
sulphuric acid, preferably at a temperature of 25° C., until it crystallises. At the
above temperature this occurs after 5 or 6 days and the product possesses a light
brown colour. At winter temperature the same process requires as many weeks
and a much darker preparation is the result.
The crystals are the hydrobromic acid salt of the new base. The salt is
carefully washed with alcohol, in which it is insoluble, in order to remove small
quantities of still unaltered amido-acetic aldehyde, then treated in hot aqueous
solution with animal charcoal and crystallised by cooling the concentrated solution.
By repetition of this purificatory process the salt is obtained in colourless glistening
prismatic crystals. It is soluble in water, especially easily in hot water, but is
almost insoluble in absolute alcohol. According to analysis it has the composition
CHNO, (HBr),
The hydrochloride, which is obtained from the hydrobromide by shaking its
aqueous solution with silver chloride, possesses similar properties.
The platinochloride is easily soluble in hot water and crystallises therefrom on
cooling in beautiful, yellowish-red, short prisms.
The free base, which is separated from its salts as an oil by very concentrated
alkali or is prepared in the well known manner by the action of moist silver oxide
on the hydrobromide or hydrochloride, is extraordinarily easily soluble in water
and in alcohol, but on the other hand is almost insoluble in ether. From warm
acetic ether, wherein it is soluble only with difficulty, it can be obtained in long.

page_text: colourless needles or prisms, which melt at 83° C. and rapidly deliquesce by
abstracting water from the air. The base has an alkaline reaction and is not
altered either by boiling with alkalies or with Fehling's solution.
If the aqueous solution of the base to which alkali has been added be shaken
with benzoyl chloride, a benzoyl derivative rapidly separates out in crystalline
flakes.
The polymeric base can be also prepared by employing hydrochloric acid
similarly to hydrobromic acid, but the process is less simple and the isolation of
the product affords great difficulties.
The base and its salts are intended for therapeutical employment.
The Preparation of a Crystalline Polymeric Base, suitable for
Medical Use, from Amido-acetic Aldehyde.
I, SYDNEY PITT, of Sutton, in the County of Surrey, Gentleman, (a communi-
cation to me from abroad by The Chemische Fabrik auf Actien vorm. E. Schering,
of 170 Müllerstrasse, Berlin,) 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 :-
As Emil Fischer has recently shown, the salts of amido-acetic aldehyde are
produced by the action of strong mineral acids on amidoacetal at ordinary
temperatures. If hydrochloric acid or hydrobromic acid is employed the salts of
these acids remain behind on evaporation in vacuum as a non-crystalline syrup.
The latter is characterised by its great solubility in water and alcohol, by its
strong reducing action on Fehling's solution and by its ready decomposition on
boiling with water or alkalies. In keeping the acid syrup for some time at ordinary
temperatures apparently only a slight change takes place, rendered visible by the
syrup browning. In reality however a part of the amido acetic aldehyde is
converted into a new crystalline base. The latter possesses the same empirical
composition as amido-acetic aldehyde, but is distinguished from it by the indifference
of the new base towards alkalies and towards Fehling's solution, as well as by the
crystallising powers and stability of its salts. Its properties indicate that it is a
polymeride of amido-acetic aldehyde.
It is most easily obtained direct from amidoacetal by employing hydrobromic
acid in the following manner. Amidoacetal is introduced into cooled hydrobromic
acid of 1.49 specific gravity as in the preparation of amido-acetic aldehyde and the
liquid after standing for five hours at the temperature of the room evaporated as
far as possible in a vacuum from a bath the temperature of which does not rise
above 60° C. The slightly yellow coloured syrup, which contains the hydro-
bromide of amido-acetic aldehyde is then allowed to stand in open vessels over
sulphuric acid, preferably at a temperature of 25° C., until it crystallises. At the
above temperature this occurs after 5 or 6 days and the product possesses a light
brown colour. At winter temperature the same process requires as many weeks
and a much darker preparation is the result.
The crystals are the hydrobromic acid salt of the new base. The salt is carefully
washed with alcohol, in which it is insoluble, in order to remove small quantities of
still unaltered amido-acetic aldehyde, then treated in hot aqueous solution with
animal charcoal and crystallised by cooling the concentrated solution. By
repetition of this purificatory process the salt is obtained in colourless glistening
prismatic crystals. It is soluble in water, especially easily in hot water, but is
almost insoluble in absolute alcohol. According to analysis it has the composition
CH N
LID

page_text: The hydrochloride, which is obtained from the hydrobromide by shaking its
aqueous solution with silver chloride, possesses similar properties.
The platinochloride is easily soluble in hot water and crystallises therefrom on
cooling in beautiful, yellowish-red, short prisms.
The free base, which is separated from its salts as an oil by very concentrated
alkali or is prepared in the well known manner by the action of moist silver oxide
on the hydrobromide or hydrochloride, is extraordinarily easily soluble in water and
in alcohol, but on the other hand is almost insoluble in ether. From warm acetic
ether, wherein it is soluble only with difficulty, it can be obtained in long colourless
needles or prisms, which melt at 83° C. and rapidly deliquesce by abstracting water
from the air. The base has an alkaline reaction and is not altered either by boiling
with alkalies or with Fehling's solution.
If the aqueous solution of the base to which alkali has been added be shaken
with benzoyl chloride, a benzoyl derivative rapidly separates out in crystalline
flakes.
The polymeric base can be also prepared by employing hydrochloric acid
similarly to hydrobromic acid, but the process is less simple and the isolation of the
product presents great difficulties.
The base and its salts are intended for therapeutical employment.
Having now particularly described and ascertained the nature of the said
invention and in what manner the same is to be performed, I declare that what
I claim is :-
:-
1. The conversion of amidoacetaldehyde into salts of a polymerised crystallised
base by the treatment substantially as described of concentrated acid solutions of
the salts of amidoacetaldehyde.
2. The manufacture of the crystallised base itself from the salts by the addition
of an alkali to a salt of the base or by the addition of oxide of silver to a halogen
salt of the base.
3. The direct manufacture of the same crystallised base, and its salts from
amidoacetal substantially as described.
4. The new products bromohydrate and chlorhydrate salts of the polymerised
base.
5. The new product polymerised amidoacetaldehyde.
Dated this 17th day of September 1894.
CARPMAEL & Co.,
Agents for the Applicant.