Improvements in the Manufacture of O-sulphamin Benzoic Acid Alkylesters, and of Anhydro-o-sulphamin Benzoic Acid.
Year: 1897

page_text: Date of Application, 15th Jan., 1897
Complete Specification Left, 6th Feb., 1897-Accepte 1, 27th Mar.. 1897
Improvements in the Manufacture of O-sulphamin Benzoic Acid
Alkylesters, and of Anhydro-o-sulphamin Benzoic Acid.
A communication from abroa I by THE CHEMISCHE FABRIK VON HEYDEN GESELL-
SCHAFT MIT BESCHRÄNKTER HAFTUNG, of Radebeul, near Dresden, Saxony,
German Empire, Manufacturers.
I, WILLIAM LLOYD WISE, of 46 Lincoln's Inn Fields, in the County of London,
Consulting Engineer and Chartered Patent Agent, do hereby declare the nature of
this invention to be as follows:→
The alkylesters of o-sulphamin benzoic acid have hitherto been produced by
treating o-sulphaminbenzoic acid. salts with iodinealkyl or by decomposing back
anhydrosulphamin benzoic acid (Berichte der Deutschen Chem. Gesellschaft 20, 1601).
These processes are not however suitable for the manufacture commercially, of
o-sulphaminbenzoic acid alkylesters for the purpose of utilizing the latter for the
production of anhydrosulphaminbenzoic acid.
The usual process for esterizing acids, by treating an alcoholic solution of the
respective acid with mineral acids has heretofore appeared impracticable for the
production of o-sulphaminbenzoic acid-alkylesters, it being known that in treating
o-sulphaminbenzoic acid with mineral acids the amide group is very readily split off.
Now my foreign correspondents have found that notwithstanding this circumstance
o-sulphaminbenzoic acid is readily esterized by treatment with alcohols, and mineral
acids under certain conditions as hereinafter described. As a main condition for the
success of the reaction and in order that the yield shall be an industrially appreciable
one, the smallest possible amounts of mineral acid, and alcobols, freed as far as
possible from water should be used. If these precautions are not observed, the yield
of ester is very considerably diminished on account of the partial decomposition of the
o-sulphaminbenzoic acid to o-sulphobenzoic acid.
:
A good yield of o-sulphaminbenzoic acid ethyl ester is obtained as follows:-
To 40 kilogrammes alcobol of 98 % there are added with stirring, 10 kilogrammes
o-sulphaminbenzoic acid, and 2 kilogrammes of concentrated sulphuric acid. The
mixture is heated to the boiling point for several hours, a return flow condenser
being used. The alcohol is afterwards distilled off, and the residue poured into cold
water, when the ester separates in the form of a quickly setting oil. By
crystallization from dilute alcohol the ester is obtained in the form of fine white
needles having a melting point of 83-84° C. Instead of using sulphuric acid, any
other mineral acid may be used; such for example as hydrochloric acid gas, other
alcohols than ethyl alcohol may also be used if desired.
I also base upon the above described improved process (which is the only one of
use at present known to my correspondents for industrial purposes) of producing
o-sulphaininbenzoic acid alkylester, an improved combination process for the pro-
duction of anhydro-o-sulphaminbenzoic acid. Certain parts of this combination
process taken separately have heretofore been described. The said combination
process comprises inter alia the above. described new process for the production of
o-sulphaminbenzoic acid alkylester, as well as a new process for the production of
pure o-sulphaminbenzoic acid from the ortho or from a mixture of o- and p-toluol-
sulphonamide. According to this invention these new processes are combined with

page_text: several known processes into one whole process for producing anhydro-o-sulphamin-
benzoic acid.
--
In carrying out the improved combination process I proceed as follows: --
1st process: I take a quantity of toluol-sulphonamide, pure ortho-amide, or a
mixture of the o- and p-amides (preferably produced according to the method of
Claesson and Wallin, Berichte der Deutschen Chem. Gesellschaft 12, 1848) and
oxidize it in an alkaline solution to o-sulphaminbenzoic acid. Well known oxidizing
agents such as ferricyanide of potassium, permanganate of potassium or manganate of
potassium or sodium may be employed for the purpose but the last two are preferred
when operating on an industrial scale.
A strongly alkaline solution of toluol sulphamide is heated to boiling point, and
oxidized by the gradual addition of potassium permanganate or potassium manganate
(see Ber. 21 243), the end of the reaction being indicated by the very slow
disappearance of the colour due to the manganate when fresh portions of the reagent
are added. The oxidized mixture is then filtered, and a precipitate formed by the
addition of hydrochloric acid. If pure o-toluol sulphonamide has been used, the
hydrochloric acid is added as long as any precipitate forms; this precipitate is pure
o-sulphaminbenzoic acid but if the solution oxidized contained a mixture of o- and
p-toluol sulphonamide, hydrochloric acid corresponding in quantity to the amount of
p-sulphaminbenzoic acid contained in the oxidation solution-is first added in slight excess.
By this means, there is obtained as a first precipitate p-sulphaminbenzoic acid with
small amounts of o-sulphaminbenzoic acid, the mixture is then filtered and the resulting
filtrate precipitated with hydrochloric acid when pure o-sulphaminbenzoic acid having
a melting point of 154-158° C. is thrown down.
In the latter case the first precipitate is stirred up in a small quantity of water (the
p-acid being very difficultly soluble in water, whilst the o-acid is very readily soluble
in that liquid), and again filtered, the filtrate therefrom neutralized, concentrated by
evaporation and reprecipitated whereby also the small quantity of o-sulphaminbenzoic
acid contained in the said first precipitate is obtained pure.
2nd process. The o-sulphaminbenzoic acid produced as above is then converted into
its alkylester, as hereinbefore described.
3rd process. The conversion of the o-sulphaminbenzoic acid alkylester into anhydro-
o-sulphaminbenzoic acid. This process may be effected, as is well known (Berichte
der Deutsch. Chem. Gesellsch. 20, 1604) by simply heating the ester alone or in an
alkaline liquid.
The ester is heated to 100-110° C., with constant stirring when alcohol separates,
and is distilled off, anhydro-o-sulphaminbenzoic acid remaining behind. Or the ester
may be sirred up in water and a solution of 1 molecule caustic soda (1:10) for each
molecule of ester allowed to flow gradually into the same, until the dissolution is
complete. The anhydro-o-sulphaminbenzoic acid may then be precipitated from its
solution by hydrochloric acid.
According to another method of carrying out this part of the combination process,
the esters are not isolated but there is added to the crude reaction mixture (which
contains o-sulphaminbenzoic acid alkyl-ester, alcohol in excess, and mineral acid) so
much dry soda as is necessary to neutralize the mineral acid and the anhydro-o-
sulphamin benzoic acid which will be produced by the conversion of the ester.
After the addition of the soda, the alcohol is distilled off, the residue diluted with
water, and filtered, and the anhydro-o-sulphaminbenzoic acid is precipitated by
hydrochloric acid.
Instead of using caustic soda, or soda, as the neutralising liquid, any other substance
having an alkaline reaction may be employed.
Dated this 15th day of January 1897.
W. LLOYD WISE,
46 Lincoln's Inn Fields, London, W.C., Chartered Patent Agent.

page_text: Improvements in the Manufacture of O-sulphamin Benzoic Acide
Alkylesters, and of Anhydro-o-sulphamin Benzoic Acid.
A communication from abroad by the CHEMISCHE FABRIK VON HEYDEN GESELLSCHAFT'
MIT BESCHRANKTER HAFTUNG, of Radebeul, near Dresden, Saxony, German
Empire, Manufacturers.
t.
I, WILLIAM LLOYD WISE, of 46 Lincoln's Inn Fields, in the County of London,
Consulting Engineer and Chartered 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 alkylesters of o-sulphamin benzoic acid have hitherto been produced by treating
o-sulphaminbenzoic acid salts with iodinealkyl or by decomposing back anhydro-
sulphaminbenzoic acid (Berichte der Deutschen Chem. Gesellschaft 20, 1601). These
processes are not however suitable for the manufacture commercially of o-sulphamin-.:
benzoic acid alkylesters for the purpose of utilizing the latter for the production of
anhydro-sulphaminbenzoic acid."
The usual process for esterizing acids, by treating an alcoholic solution of the
respective acid with mineral acids has heretofore appeared impracticable for the
production of o-sulphaminbenzoic acid-alkylesters, it being known that in treating
o-sulphaminbenzoic acid with mineral acids the amide group is very readily split off.
Now my foreign correspondents have found that notwithstanding this circumstance
o-sulphaminbenzoic acid is readily esterized by treatment with alcohols and mineral
acids under certain conditions as hereinafter described. As a main condition for the
success of the reaction and in order that the yield shall be an industrially appreciable
one, the smallest possible amounts of mineral acid and alcohols freed as far as possible
from water should be used. If these precautions are not observed, the yield of ester
is very considerably diminished on account of the partial decomposition of the
o-sulphaminbenzoic acid to o-sulphobenzoic acid.
A good yield of o-sulphamin benzoic acid ethyl ester is obtained as follows:-
To 40 kilogrammes alcohol of 98% there are added with stirring, 10 kilogrammes
o-sulphaminbenzoic acid, and 2 kilogrammes of concentrated sulphuric acid. The
mixture is heated to the boiling point for several hours, a return flow condenser
being used. The alcohol is afterwards distilled off, and the residue poured into cold
water, when the ester separates in the form of a quickly setting oil. By crystallization
from dilute alcohol the ester is obtained in the form of fine white needles having a
melting point of 83-84° C. Instead of using sulphuric acid, any other mineral
acid may be used; such for example as hydrochloric acid gas, other alcohols than
ethyl alcohol may also be used if desired.
I also base upon the above described improved process (which is the only one of
use at present known to my correspondents for industrial purposes) of producing
o-sulphaminbenzoic acid alkylester, an improved combination process for the
production of anhydro-o-sulphaminbenzoic acid. Certain parts of this combination
process taken separately have heretofore been described. The said combination.
process comprises inter alia the above described new process for the production of
o-sulphaminbenzoic acid alkylester, as well as a new process for the production of
pure o-sulphaminbenzoic acid from the ortho or from a mixture of o- and p-toluol-
sulphonamide. According to this invention these new processes are combined with
several known processes into one whole process for producing anhydro-o-sulphamin- .
benzoic acid.

page_text: In carrying out the improved combination process I proceed as follows :—
1st process: I take a quantity of toluol-sulphonamide, pure ortho-amide, or a
mixture of the o- and p-amides (preferably produced according to the method of
Claesson and Wallin, Berichte der Deutschen Chem. Gesellschaft 12, 1848) and
oxidize it in an alkaline solution to o-sulphaminbenzoic acid. Well known oxidizing
agents such as ferricyanide of potassium, permanganate of potassium or manganate
of potassium or sodium may be employed for the purpose but the last two are preferred.
when operating on an industrial scale.
A strongly alkaline solution of toluol sulphamide is heated to boiling point, and
oxidized by the gradual addition of potassium permanganate or potassium manganate
(see Ber. 21 243), the end of the reaction being indicated by the very slow dis-
appearance of the colour due to the manganate when fresh portions of the reagent
are added. The oxidized mixture is then filtered, and a precipitate formed by the
addition of hydrochloric acid. If pure o-toluol sulphoamide has been used, the hydro-
chloric acid is added as long as any precipitate forms; this precipitate is pure
o-sulphaminbenzoic acid, but if the solution oxidized contained a mixture of o- and
p-toluol sulphonamide, hydrochloric acid corresponding in quantity to the amount of
p-sulphaminbenzoic acid contained in the solution is first added in slight excess. By
this means, there is obtained as a first precipitate p-sulphaminbenzoic acid with
small amounts of o-sulphaminbenzoic acid, the mixture is then filtered and the
resulting filtrate precipitated with hydrochloric acid when pure o-sulphaminbenzoic
acid having a melting point of 154-158° C. is thrown down.
In the latter case the first precipitate is stirred up in a small quantity of water
(the p-acid being very difficultly soluble in water, whilst the o-acid is very readily
soluble in that liquid), and again filtered, the filtrate therefrom neutralized,
concentrated by evaporation and reprecipitated whereby also the small quantity of
o-sulphaminhenzoic acid contained in the said first precipitate is obtained pure.
2nd process. The o-sulphaminbenzoic acid produced as above is then converted
into its alkylester, as hereinbefore described.
3rd process. The conversion of the o-sulphaminbenzoic acid alkylester into
anhydro-o-sulphaminbenzoic acid. This process may be effected, as is well known
(Berichte der Deutsch. Chem. Gesellsch. 20, 1604) by simply heating the ester alone
or in an alkaline liquid.
The ester is heated to 100-110° C., with constant stirring when alcohol separates,
and is distilled off, anhydro-o-sulphaminbenzoic acid remaining behind. Or the
ester may be stirred up in water and a solution of 1 molecule caustic soda (1: 10}
for each molecule or the ester allowed to flow gradually into the same, until the
dissolution is complete. The anhydro-o-sulphaminbenzoic acid may then be
precipitated from its solution by hydrochloric acid.
According to another method of carrying out this part of the combination process,
the esters are not isolated but there is added to the crude reaction mixture (which
contains o-sulphaminbenzoic acid alkylester, alcohol in excess, and mineral acid) so
much dry soda as is necessary to neutralize the mineral acid and the anhydro-o-
sulphaminbenzoic acid which will be produced by the conversion of the ester.
After the addition of the soda, the alcohol is distilled off, the residue diluted with
water and filtered, and the anhydro-o-sulphaminbenzoic acid is precipitated by
hydrochloric acid.
Instead of using caustic soda, or soda, as the neutralizing liquid, any other
substance having an alkaline reaction may be employed.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed I declare that what I
claim is
1. The manufacture of o-sulphaminbenzoic-acid alkylesters, by converting o-
sulphaminbenzoic acid into an alkylester by heating it in an alcoholic solution with
a comparatively small quantity of a mineral acid and distilling off the alcohol,
substantially as described..

page_text: 2. The manufacture of anhydro-o-sulphaminbenzoic acid, by (A) oxidation of o-
toluolsulphonamide, or of a mixture of o- and p-toluolsulphonamide to sulphamin-
benzoic acid and separation of the o- and p-sulphaminbenzoic acid by fractional
precipitation, or by utilizing the difference in solubility of the two acids in water,
(B) conversion of the o-sulphaminbenzoic acid into an alkylester by heating it with
a small quantity of a mineral acid in an alcoholic solution and (C) conversion of the
ester mentioned under B, into its anhydro combination by heating it, or by treating
it with an alkaline reagent as set forth.
3. The manufacture of pure o-sulphamin benzoic acid from o-toluolsulphonamide or
from a mixture of o- and p-toluolsulphonamide by oxidation in alkaline solution with
a suitable oxidizing agent such as manganate or permanganate salts, and in the
case of the mixture separating the o- and p-sulphaminbenzoic acid by fractional
precipitation substantially as described.
1000
W. LLOYD WISE,
46 Lincoln's Inn Fields, London, W.C., Chartered Patent Agent.