Improvements in the Manufacture of Para-phenetolcarbamide and Para-anisolcarbamide and their Amido-derivatives.
Year: 1892

page_text: Date of Application, 29th Jan., 1892
Complete Specification Left, 28th Oct., 1892-Accepted. 10th Dec., 1892
PROVISIONAL SPECIFICATION.
Improvements in the Manufacture of Para-phenetolcarbamide and
Para-anisolcarbamide and their Amido-derivatives.
1, JOSEPH BERLINER BLAU, Ph. D., of Sosnowice (Russian Poland), Chemist,
do hereby declare the nature of this invention to be as follows :-
This invention relates to the manufacture of para-phenetolcarbamide and para-
anisolcarbamide and their amido-derivatives.
The para-phenctolcarbamide CH
OCHÊ (1)
H
CONH, (4)
was first prepared by
the inventor in the year 1883 from cyanate of potassium and hydrochloride of
p-phenetidine, and forms a substance which has an extremely sweet taste and is
innocuous when taken internally, thus appearing capable of being utilized in the
arts as a saccharine matter that may serve as a substitute for sugar. This mode
of preparation, however, is very expensive, and is dangerous on account of the
poisonous properties of the cyanate of potassium, and, therefore, quite unsuitable
for carrying into practice on a large scale.
The process forming the subject of this invention is intended to remedy these
defects.
The said process is based essentially upon the formation of an intermediate
phosgene COC, and 2 molecules of p-phenetidine CH
NH,
which inter-
mediate combination or product forms with ammonia the p-phenetolcarbamide in ·
theoretical quantity. The action of phosgene gas upon aniline may, moreover,
cause the formation of double substitutes of urea, which would obviously have an
influence on the yield. To augment the yield, it is requisite. to operate with
solutions that are not too concentrated, and to avoid heating during the reaction.
Hence the p-phenetolcarbamide is best prepared according to this invention in the
following manner :-
1 kilogram of p-phenetidine is dissolved in a suitable solvent, for instance in
from 2 to 3 times its quantity of benzol or toluol, this solution being gradually
poured into 2.5 kilograms of a 20 per cent. solution of phosgene in benzol or toluol.
There separates forthwith hydrochloride of phenetidine, which is filtered from
the solution after a certain time has elapsed (preferably after from to 1 hour)
according to the following equation :—
1) 2 CH
+ COC₁₂ = CHÁ
CH
H
NH,
NH,HCI
\COCI
[Price 8d.]

page_text: To the filtrate is added, or into the same is introduced, such quantity of
ammonia (NH) as is calculated to correspond to two molecules of ammonia (NH,).
The filtrate may also be shaken in an aqueous solution of ammonia. The reaction
takes place according to the following equation
COCI
NOONH,
The solvent is now distilled off and the residuum of p-phenetolcarbamide is
washed with cold water and crystallized by means of boiling water. The p-phene-
tolcarbamide forms, when in a state of purity, white needles having a melting point
of one hundred and sixty degrees (160°) centigrade, not easily soluble in cold water
but readily soluble in hot water, as well as in all ordinary solvents, such as 1
alcohol, ether, benzol and the like. If the p-phenetidine is replaced by the
p-anisidine, the corresponding p-anisolcarbamide (which has also a very sweet
✓OCH,
1
1
AL falling cavations —
\COCI
\CONH
The para-anisolcarbamide forms, in a state of purity, white needles which are
readily soluble in hot water and in the usual solvents, such as alcohol and
ether. Its melting point has been fixed at one hundred and fifty four degrees
(154°) centigrade, but it may be remarked that this determination has not yet
been verified. The amido-derivatives of these carbamides, which have likewise a
sweet taste, are preferably obtained by nitrating these carbamides to their
mononitro-derivatives, and by reducing with tin and hydrochloric acid to convert.
them into amido-compounds.
Dated this 29th day of January 1892.
D. YOUNG & Co.,
11 & 12, Southampton Buildings, London, W.C., Agents for the Applicant.
COMPLETE SPECIFICATION.
Improvements in the Manufacture of Para-phenetolcarbamide and
Para-anisolcarbamide and their Amido-derivatives.
I JOSEPH BERLINERBLAU, Ph. D. of Sosnowice, (Russian Poland), Chemist, 3
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:
This invention relates to the manufacture of para-phenetolcarbamide and para-
anisolcarbamide and their amido-derivatives.
3

page_text: ‚ОCH (1)
The para-phenetolcarbamide C.H
was first prepared by
H
N
\CONH, (4)
the inventor in the year 1883 from cyanate of potassium and hydrochloride of
p-phenetidine, and forms a substance which has an extremely sweet taste and is
innocuous when taken internally, thus appearing capable of being utilized in the
arts as a sacchariue matter that may serve as a substitute for sugar. This
mode of preparation, however, is very expensive and is dangerous on account of
the poisonous properties of the cyanate of potassium, and, therefore, quite unsuit-
able for carrying into practice on a large scale.
The process forming the subject of this invention is intended to remedy these
defects.
The said process is based essentially upon the reaction of phosgene and
p-phenetidine CH
✓OC,H,
NH,
and the treatment of the intermediate combinations
thus formed, with ammonia. The reaction takes place according to the following
equations ;-
он
VOC,H,
NH,
OC,H
+ COCI,= CH
+ HCl
NHCOC1
or, if a second molecule of HCl is separated ;—
✓OCH
✓OC,H₂
CH
+ COC₁₂ = CH⭑
+ 2 HCl.
NH,
ANCO
- It matters not whether, by the action of the phosgene upon the phenetidine
or its salts, p-phenetidine-carbonylchloride CH
OCH
or p-phenetoliso-
NHCOCI
cyanate CH
OC,H
\NCO
(boiling point about 235° centigrade) are formed as
intermediate products, which are liquid. combinations having a strong smell; by
the subsequent action of the ammonia, phenetolcarbamide is always produced :—
✓OC,H
ATT
ATTI
OC,H,
HCI
NHCOCI
OC₂H
NHCONH,
✓ OC,H
CH
+ NH₁ = CH⭑
NCO
NHCONH.
Hence the p-phenetolcarbamide is prepared in the following manner ;-
1 kilogram of-p-phenetidine is dissolved in a suitable solvent, for instance in
from 2 to 3 times its quantity of benzol or toluol, this solution being gradually
poured into 1-3 to 2.5 kilograms of a 20 per cent. solution of phosgene in benzol or
toluol. There separates forthwith hydrochloride of phenetidine, which is filtered
from the solution after a certain time has elapsed (preferably after from
1 hour).
•
to
To the filtrate is added, or into the same is introduced a quantity of ammonia
(NH), until an excess of NH, is noticed by the smell. The filtrate may also be
shaken in an aqueous solution of ammonia.

page_text: The solvent is now distilled off and the residuum of p-phenetolcarbamide is
washed with cold water and crystallized by means of boiling water. The p-phene-
tolcarbamide forms, when in a state of purity, white needles having a melting
point of one hundred and sixty degrees (160°) centigrade, not easily soluble in
cold water but readily soluble in hot water, as well as in all ordinary solvents, such 5
as alcohol, ether, benzol and the like.
In the above described reaction, a solvent may be dispensed with and a high

page_text: The para-anisol-carbamide forms, in a state of purity, white needles which are
readily soluble in hot water and in the usual solvents, such as alcohol and ether.
Its melting point has been fixed at one hundred and fifty four degrees
(154°) centigrade, but it may be remarked that this determination has not yet
been verified. The amido-derivatives of these carbamides, which have likewise &
sweet taste, are preferably obtained by nitrating these carbamides to their mono-
nitro-derivatives, and by reducing with tin and hydrochloric acid to convert them
into amido-compounds.
Having now particularly described and ascertained the nature of my said inven-
tion, and in what manner the same is to be performed, I declare that what I
claim is ;-
Dated the 27th day of October 1892,
D. YOUNG & Co.,
11 & 12, Southampton Buildings, London, W.C., Agents for the Applicant..
D. YOUNG & Co.,
11 & 12, Southampton Buildings, London, W.C., Agents for the Applicant..