Improvements in the Manufacture or Production of Pharmaceutical Compounds.
Year: 1899

page_text: Date of Application, 6th Nov., 1899
Complete Specification Left, 25th July, 1900-Accepted, 25th Aug., 1900
[Communicated from abroad by THE FARBENFABRIKEN vormals FRIEDRION
BAYER & Co, of Elberfeld, Germany ]
Improvements in the Manufacture or Production of Pharmaceutical
Compounds.
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings,
Chancery Lane, in the County of London, Patent Agent, do hereby declare the
nature of this invention to be as follows:-
It is well known that the alkyl ethers of para-oxy-meta-amidobenzoic acid
possess valuable therapeutic properties, inasmuch as they represent very effec-
tive local anaesthetics.
My foreign correspondents have now found a new and useful process for pio-
ducing these compounds The new process consists in allowing suitable diazo
compounds to act on the alkyl etheis of para-oxybenzoic acid The azo-dye-
stuffs thus obtained are then split up by means of reducing agents, para-oxy-
meta-amido-benzoic ethers being the result. The reduction proceeds, if, for
instance, diazobenzene has been used, according to the following equation (R mean-
ing any alkyl radiole).-
0 is stirred into 20 parts of a 6 per cent. sodium carbonate solution
After
almost the whole has dissolved, the mixture 18 cooled down to zero by means
of ice Subsequently, somewhat more than the calculated quantity of diazo-
benzene sulphonic acid, mixed with ice water, is rapidly added to the reaction
The mixture thus obtained 18 stirred for, say, 2 hours, at about zero,
mass.
D071

page_text: It 18 desirable
until the reaction is finished, and a clear solution results The dye-stuff is
then separated by the addition of common salt, filtered off, died, and pulverized
It can directly be used for the preparation of the oxyamidobenzoic ethei
1 pait
of the dye-stuft thus produced is pulverized, mixed with 1 part of water, and
slowly introduced into 4 parts of a mixture prepared from stannous chlonde
and hydrochloric acid (1 litre of this mixture containing 330 grammes of stan-
nous chloride), while being energetically stirred The reduction sets in imme-
diately, the temperature of the reaction mixture 11sing the while
that the temperature should not unduly se After the reaction is finished,
the mass is cooled, and the separated product is filtered off and washed with a
solution of common salt Subsequently, it is dissolved in water, and the result-
ing solution is filtered (if, necessary), 'and then nuxed with a sodium carbonate
solution, the fice ethylic ether of para-oxy-meta-amido-benzoic acid being thus
precipitated By a recivstallisation from water, this body can be obtained in
a pure state
The process proceeds in an analogous manner, if other alkyl ethers of para-
oxy-benzoic acid, such as the methylic ether and other diazo compounds, or other
reducing agents, are employed
As a matter of course, my foreign correspondents do not intend to confine
themselves to the particulars given in the above example, as this is merely
typical, and can be varied within wide limits
Dated this the 6th day of November 1899
NEWTON & SON
Agents for the Applicant
Improvements in the Manufacture or Production of Pharmaceutical
Compounds.
I, HENRY EDWARD NEWTON, of the Office for Patents, 6, Bream's Buildings,
Chancery Lane, in the County of London, 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
-
It is well known that the alkyl ethers of para-oxv-meta-amidobenzoic acid
possess valuable therapeutic properties, inasmuch as they represent very effec-
tive local anesthetics
My foreign correspondents have now found a new and useful process for pro-
ducing these compounds The new process consists in allowing suitable diazo
compounds to act on the alkyl ethers of para-oxybenzoic acid
The azo-dye-
stuffs thus obtained are then split up by means of reducing agents, para-oxy-
meta-amido-benzoic ethers being the result The reduction proceeds if, for
instance, diazobenzene has been used, according to the following equation (R mean-
ing any alkyl radicle) :-

page_text: In order to illustrate the new process more fully, the following example 15
given, the parts being by weight.-
is stirred into 20 parts of a 6 per cent sodium carbonate solution When
almost the whole mass has dissolved, the mixture 18 cooled down to zero by means
mass
of
of ice
Subsequently, somewhat more than the calculated quantity of diazo-
benzene-sulphonic acid, mixed with ice water, 18 rapidly added to the reaction
The mixture thus obtained 18 stiried for, say, 2 hours, at about zeio,
until the reaction is finished, and a clear solution results The dye-stuff 18
then separated by the addition of common salt, filtered off, dried, and pulverized
The dye-stuff thus produced can be used for the preparation
the oxyamidobenzoic ether as follows:-1 part of the dye-stuff is pulverized,
mixed with one part of water, and slowly introduced into 4 parts of a mixture
prepared from stannous chloride and hydrochloric acid (1 litre of this mixture
containing 330 grammes of stannous chloude), while being energetically stirred
The reduction sets in immediately, the temperature of the reaction mixture
118ing the while. It is desirable that the temperature should not unduly rise
After the reaction is finished, the mass is cooled, and the separated product 19
filtered off and washed with a solution of common salt Subsequently, it 19
dissolved in water, and the resulting solution is filtered (if necessary), and then
mixed with a sodium carbonate solution, the fiee ethylic ether of para-oxy-meta-
amido-benzoic acid being thus precipitated By a recrystallisation from water,
this body can be obtained in a pure state'
The process proceeds in an analogous manner, if other alkyl ethers of para-
oxy-benzoic acid, such as the methvlic ether and other diazo-compounds or other
reducing agents, are emploved
As a matter of course, my foreign correspondents do not intend to confine
themselves to the particulars given in the above example, as this is meielv
typical, and can be varied within wide limits
Having now particularly described and ascertained the nature of the said
invention and in what manner the same is to be performed, as communicated
to me from abroad, I declare that what I claim 19.-
1 The process for the production of the alkyl ethers of para-oxy-meta-amido-
benzoic acid, having the following general formula.-
(R meaning, in this formula, any alkyl radicle), which process consists in com-
bining the alkyl ethers of para-oxybenzoic acid with suitable diazo-compounds.
40 and then splitting up the resulting azo-dye-stuffs by means of reducing agents,
substantially as herein before described.
2. The process for the production of the alkyl ethers of para-oxy-meta-amido

page_text: benzoic acid, which process consists
defined in the above Claim 1, to the
as herein before described.
in subjecting the azo-coloring matters
action of reducing agents, substantially