The Manufacture or Production of Chemical Compounds Containing Iodine.
Year: 1894

page_text: Date of Application, 4th July, 1894
Complete Specification Left, 4th Apr., 1895-Accepted, 11th May, 1995
[Communicated from abroad by THE FARBENFABRIKEN, vormals FRIEDRICH
BAYER & Co., of Elberfeld, Germany, acting on behalf of Dr. ALEXANDER
CLASSEN, of Aix-la-Chapelle, Germany.]
The Manufacture or Production of Chemical Compounds Containing
Iodine.
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:-
My foreign correspondents have described in the Specifications of Letters Patent
No. 507989, 18021%, and 7026", the production of a great number of iodine
compounds which are obtained from phenol or phenol-like substances, and can be
used for pharmaceutical purposes.
My foreign correspondents have now found that new iodine compounds, also
suitable for pharmaceutical purposes, can be obtained, on treating in a suitable
manner, with iodine or substances capable of giving iodine, either the hydroxy
derivatives of triphenylmethane or analogues thereof, or the hydroxy derivatives
of the substituted triphenylmethane or analogous products (such as benzines,
aurines, rosolic acid, phthaleines, or the like), or secondary aromatic amines, such
as diphenylamine, the analogues thereof, or derivatives of such secondary amines,
or the tertiary aromatic amines corresponding to the last defined secondary amines.
The researches of my foreign correspondents have shewn, that hydroxy
triphenylmethanes and the analogues thereof, can readily be converted into iodine
compounds, i.e., by dissolving them in alkalies, adding iodine, and subsequently
precipitating the finished iodine compounds with the aid of acids.
The iodine products thus obtained differ from the iodine compounds hitherto
produced, as they possess a strong acid nature, and are therefore readily soluble in
alkalies, and also (which is of special value) are capable of forming salts that can
be isolated with readiness. These iodine compounds are destitute of any smell, and
my foreign correspondents propose to use these iodine products, and the salts
derived therefrom, for pharmaceutical purposes.
The iodine can be employed either dissolved in a solution of potassium iodide, or
any other suitable solvent, or in the form of iodides, with the addition of agents
capable of liberating iodine (for instance, chloride of lime, chlorine, bromine, or
the like). According to the researches of my foreign correspondents, the electric
current can also be used most profitably in order to liberate iodine from the iodine
compounds. Iodine chloride, or the combination of iodine chloride and muriatic
acid, or the like agents, can be used with the same result.
The production of the iodine compounds hereinbefore defined, is illustrated by
the following examples. The parts are by weight:
FIRST EXAMPLE.
PRODUCTION OF AURINE TRI-IODIDE BY MEANS OF IODINE AND POTASSIUM
חומIAI

page_text: PRODUCTION OF TRI-10DIDE OF ROSOLIC ACID FROM ROSOLIC ACID, IODINE,
AND POTASSIUM IODIDE.
30 parts of rosolic acid are dissolved in 150 parts of water, to which 36 parts of
sodium hydroxide had been added. The resulting liquid, while being heated on
the water bath, is mixed with a solution prepared from 76 parts of iodine, 80 parts
of potassium iodide, and 600 parts of water." The resulting clear dark-red solution
is heated during half an hour on the water bath. After cooling, the triiodide
formed is precipitated in the form of red flakes, by adding muriatic acid. It is
filtered off, redissolved in soda-lye, and precipitated again with the aid of muriatic
acid. It may be further purified by dissolving in chloroform, and separating by
means of ligroine. The tri-iodide thus obtained forms red flakes.
The tri-iodide of rosolic acid easily dissolves in the usual organic solvents (except
ligroine), at high temperatures, whilst it is soluble with greater difficulty in the
said solvents at ordinary temperature. It is insoluble in water and acids, but
readily dissolves in alkalies. It is capable of forming salts with readiness, and is
entirely free from smell, and stable, when in contact with the moist air, or when
exposed to light. Iodine is liberated, when it is heated alone or with acids.
Its formula is CHO, which requires 55-77 per cent. of iodine; my foreign
correspondents have found by analysis 56-10 and 55'08 per cent. of iodine.
This tri-iodide of resolic acid can also be produced by the process illustrated by
the second example, the corresponding quantity of rosolic acid being substituted
for the aurine. In this case, the alkaline solution is slightly heated during
electrolysis.
According to the researches of my foreign correspondents, phenolphthaleine,
when treated in an alkaline solution with iodine and potassium iodide, is converted
into different products, according as the process is carried out at low or elevated

page_text: temperatures. The products thus formed, however, are allied, and one can be
transformed into either of the others, as will be evident from the following:-
-
CONVERSION OF PHENOL PHTHALEINE INTO PHENOL PHTHALËINE
TETRAIODIDE AT LOW TEMPERATURE.
30 parts of phenol phthalëine (the parts are by weight) are dissolved in 100 parts
of water, to which 40 parts of sodium hydroxide are added. This liquid is mixed
with a solution prepared by dissolving 100 parts of iodine and 120 parts of
potassium iodide in 400 parts of water, care being taken that the temperature does
not rise above 20 degrees Centigrade. The original red colour of the alkaline
solution of phenol phthaleine then turns into deep blue. The resulting liquid is
cooled, and subsequently acidulated with cold inuriatic acid. An amorphous,
yellowish-brown substance is thus precipitated, which purified by carefully
washing with a solution, in water, of potassium iodide, and with water.
According to the researches of my foreign correspondents, the wet precipitate,
when heated at elevated temperatures (say, at about 100 degrees Centigrade), is
converted into a white substance which is the phenolphthaleine tetraiodide, whilst
the aforesaid brownish product produced at low temperature is a combination of
equal molecular proportions of phenolphthaleine and water. This latter product is
purified by dissolving the precipitate not dried in chloroform, and separating again
with the aid of ligroine. When subsequently dried in vacuo, it becomes a yellowish
powder, entirely free from smell, and perfectly stable when in contact with the air,
or when exposed to light. It possesses the formula CH40 + H₂O, which
requires 60-3 per cent. of iodine, my foreign correspondents having found by analysis
60-05 er cent. of iodine. Its solubility and its other properties are identical with
those of the white phenol-phthaleine tetra-iodide which can be obtained at elevated
temperatures, for instance, by means of the process illustrated by the following
(fifth) example.-
-
20
PRODUCTION OF PHENOL PHTHALËINE TETRAIODIDE AT ELEVATED
TEMPERATURE.
If, in the process illustrated by the preceding fourth example, after the addition
of iodine, the deep blue coloured solution is heated for some time by means of a
steam bath, the deep blue colour is changed into yellowish brown. On subsequently
adding muriatic acid, a greyish white body is precipitated, which is purified by
thoroughly washing with water, or dissolving in soda-lye, and precipitating with
acide. The phenol phthaleine tetra-iodide thus obtained is a white powder.
10
My foreign correspondents assume that the lactone nucleus is loosed during the
production of the aforesaid yellowish phenol phthaleine tetra-iodide, which has
the formula CH₁O + H₂O. This yellowish product can be converted into
the white iodine compound, and, inversely, the former can be obtained from the
latter. For instance, if the white product is dissolved in soda lye, and this alkaline
solution, when carefully cooled, is acidulated by means of muriatic acid, the yellow
compound having the last mentioned formula is precipitated. The white product,
however, is obtained when the alkaline solution is heated until the colour has
changed, and is then acidulated by ineans of muriatic acid.
Phenol phthaleine tetra-iodide is insoluble in water and ligroine. It easily
dissolves in the other organic solvents, at elevated temperatures, whilst it dissolves
with less readiness at low temperatures in these solvents. It is most soluble in hot
chloroform. It is insoluble in acids, and readily dissolves in alkalies. It is also
capable of forming salts, and is free from smeli, and stable, when exposed to moist
air or to light. Its formula is CHO, which requires 62.1 per cent. of iodine,

page_text: SIXTH EXAMPLE.
PRODUCTION OF PHENOL PHTHALEINE TETRA-IODIDE BY ELECTROLYSIS.
A solution prepared by dissolving 140 parts of potassium iodide in 200 parts of
water, is added to a solution containing 30 parts of phenol phthalëine, 35 parts of
sodium hydroxide, and 100 parts of water. The resulting liquid is subjected, during
some hours, to the action of an electric current of 1.5 ampères per square decimeter
of electrode surface. The end of the reaction is distinguishable by the change in
colour. The mass is then heated until the blue colour has changed into yellowish
brown. The phenol phthalëine tetra iodide is then precipitated with the aid of
muriatic acid.
Analogous iodine compounds are obtained, if other hydroxy derivatives of
triphenylmethane, or its analogues, or substitution derivatives of such hydroxy
compounds, are used in place of aurine or rosolic acid, or phenol phthalëine, used in
the foregoing examples.
As above mentioned, the iodine compounds herein before defined are capable of
forming salts, which can readily be separated.
It forms
For instance, salts of phenol phthaleine tetra iodide can be obtained from the
aforesaid yellowish or white tetraiodide. The zinc salt of phenolphthaleine tetra-
iodide can be obtained on adding an alkaline solution of zinc oxide to an alkaline
solution of the tetraiodide. The solution remains clear, and the said zinc salt
separates as a white flaky precipitate when the solution is carefully neutralized by
means of acetic acid. The iron salt results on mixing a solution, in alcohol, of the
tetraiodide with a concentrated watery solution of ferric chloride.
yellowish-red flakes. The aluminium salt can be obtained in a manner analogous
to that described for the above mentioned zinc salt. The bismuth salt and mercury
salt can be prepared by slowly adding an alkaline solution of phenol phthaleine
tetraiodide to a solution of a bismuth or mercury salt, acidulated with acetic acid,
taking care that the acetic acid remains in excess. The mercury salt of phenol
phthaleine tetraiodide instantly separates as a light yellow flaky precipitate, whilst
the bismuth salt separates only after diluting with water, and after allowing the
liquid to stand during some time. The bismuth salt forms white flakes.
All these salts, and the analogous salts derived from the other iodine compounds
hereinbefore defined, are entirely free from smell, and are suitable for use for
pharmaceutical purposes. They are not decomposed by light or moisture.
In order to produce salts of the iodine compounds hereinbefore defined, my foreign
correspondents do not limit themselves to the particulars above given, as these salts
can be prepared by means of all methods known and in use for producing analogous
phenol salts. The iodine or potassium iodide used for preparing the said iodides,
may also be replaced by other agents affording the same result; for instance, iodine
chloride, or the combination of iodine chloride with muriatic acid or the like.
My foreign correspondents have further found, that new iodine compounds can
be prepared by allowing iodine to act (in the presence of an agent capable of
decomposing the hydroiodic acid formed during the process) on secondary aromatic
amines, such as diphenylamine, its analogues, or on derivatives of secondary amines,
or on the tertiary aromatic amines corresponding to these secondary amines. The
iodine products thus obtainable are distinguished by their strong antiseptic properties,
and by the property that they are entirely free from smell (unlike other antiseptic
iodine products), and that they can be obtained with greatest readiness in crystallised
form. My foreign correspondents therefore propose to use these iodine products
for pharmaceutical purposes, that is to say, as substitutes for iodoform and the like.
According to the researches of my foreign correspondents, for instance, mercuric
oxide may be profitably employed for decomposing the hydroiodic acid formed

page_text: during the action of iodine on the said secondary or tertiary amines. Other agents,
however, can also be used, provided they are able to combine with the hydroiodic
acid, or to decompose the latter.
The researches of my foreign correspondents have also shown that the last-defined
iodine compounds can be readily converted into derivatives by treatment with
different agents (such as acid chlorides, acid anhydrides, or the like, nitrous acid,
or the like), and that these derivatives likewise possess antiseptic properties.
The production of these iodine compounds derived from secondary or tertiary
aromatic amines, is illustrated by the following two examples, the parts being
by weight.
A mixture containing 50 parts of carbazol, 200 parts of yellow mercuric oxide,
200 parts of powdered iodine, and 2000 litres of alcohol (in case the parts are kilos.
by weight) is heated to boiling point during three hours in a vessel provided with
reflux condenser. The boiling liquid is filtered, and the resulting filtrate is
poured into 2000 litres of cold water, in which 200 parts of potassium iodide have
been dissolved, in order to prevent a precipitation of the mercuric diiodide. A
light yellow product separates, which is filtered off and washed with warm water,
until the droppings no longer contain iodine or mercury. The iodine product is
thus obtained in pure state, as an amorphous mass. When crystallised from hot
alcohol, or hot glacial acetic acid, it forms yellow scales melting at 184 degrees
Centigrade.
The carbazol diiodide thus formed is insoluble in water, readily dissolves in
benzene ether, hot alcohol, chloroform, and glacial acetic acid. Iodine is liberated
when it is heated alone or with sulphuric or nitric acid. It is not altered at
ordinary temperatures by alkalies or acids. It is entirely free from smell, and
possesses the formula:
PRODUCTION OF DIPHENYLAMINE DIIODIDE.
A mixture containing 50 parts of diphenylamine, 200 parts of mercuric oxide,
250 parts of iodine, and 2000 litres (in case the parts are kilos. by weight) of
alcohol, is heated to boiling during two hours in a vessel provided with a reflux
condenser. The resulting liquid is filtered, and the filtrate thus obtained is mixed
with a solution prepared by dissolving 200 parts of potassium iodide in 2000 litres
of water (in case the parts are kilos. by weight). The resulting dark-grey colored
crystalline precipitate is filtered off, dissolved in alcohol, and treated with bone
dust. On adding water to the filtered alcoholic solution; the iodine product is.
precipitated in the form of brilliant scales, which become clear as glass, and
pellucid, after treating them again with bone dust in alcoholic solution, and,

page_text: subsequently precipitating with water. This iodine compound melts at 129 degrees
Centigrade.
Diphenylamine diodide thus produced, is insoluble in water, and readily dissolves
in the usual organic solvents. It is not decomposed by a treatment with dilute
acids and alkalies. Iodine is liberated when it is boiled with sulphuric or nitric
acid, or when it is heated in a capillary tube at 200 degrees Centigrade. It is
without any smell, non-poisonous, and possesses strong antiseptic properties. My
foreign correspondents have ascertained by analysis that this iodine compound has
the following formula:
This formula requires 60·24 per cent. of iodine, and 3.33 per cent. of nitrogen..
my foreign correspondents having found 60-4 per cent. of iodine, and 3.45
of nitrogen.
per
cent.
Similar iodine compounds are obtained if, in the processes illustrated by the
foregoing seventh and eighth examples, other secondary aromatic amines or tertiary
amines, or derivatives thereof, be used in place of carbazol or diphenylamine.
These iodine products in general show properties similar to those of the last-named
two iodine products, viz., carbazol diiodide and diphenylamine diodide.
As above mentioned, these iodine products can easily be converted into certain
derivatives which also possess antiseptic properties. The production of two of
such derivatives is illustrated by the following ninth and tenth examples: The
parts are by weight.
1
CONVERSION OF DIPHENYLAMINE DIODIDE INTO NITROSO DIPHENYLAMINE
DIODIDE.
•
30 parts of diphenylamine diiodide are dissolved in 500 parts of absolute alcohol,
and 60 litres (in case the parts are kilos. by weight) of fuming muriatic acid
(specific gravity 1-19) are then added. After cooling with ice, a cooled solution
prepared by dissolving 60 parts of sodium nitrite in 100 parts of water is slowly
introduced. The nitroso compound, which separates at once, is filtered off after
adding a small quantity of ice water, and washed with a small quantity of alcohol.
.It is then dissolved in absolute alcohol, and this solution is then treated with bone
dust. On allowing the filtered alcoholic solution to cool, the nitroso compound
remains in long, fine yellow scales melting at from 119 to 120 degrees.
It readily dissolves at elevated temperature in the usual organic solvents, less
readily at ordinary temperature. It is insoluble in water, and becomes decomposed
when treated with strong acids, or when heated on a platinum plate, nitrous acid
and iodine being thus liberated. It is absolutely free from smell, and my foreign
correspondents have ascertained by analysis that it has the following formula :-

page_text: This formula requires 48-28 per cent. of iodine, my foreign correspondents having
found 48-31 per cent. of iodine.
My foreign correspondents have described in the preceding examples seven and
eight, some distinct methods of practically producing the iodine compounds herein-
before referred to. Naturally they do not limit themselves to the directions
given, as these can be varied. For instance, iodides, such as potassium iodide or
the like, and any agent capable of liberating iodine, can be used in place of free
iodine used in the last named examples. The combination of iodine chloride and
muriatic acid, or similar agents, can also be used, in order to prepare the last-
defined iodine products.
These iodine compounds, when treated in a suitable manner with acid chlorides,
or acid anhydrides, are transformed into acid derivatives, and when treated with
uitrous acid or the like, they are converted into nitroso products. According to
the researches of my correspondents, these acid derivatives and nitroso compounds
possess technical value, as they can be used as antiseptics in the same manner as.
the original iodine compounds hereinbefore defined.
Dated this 4th day of July 1894.
NEWTON & SON,
Agents for the Applicant.

page_text: The Manufacture or Production of Chemical Compounds Containing
Iodine.
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 :-
My foreign correspondents have described in the Specifications of Letters Patent
No. 5079, 180210, and 70261, the production of a great number of iodine compounds
which are obtained from phenol, or phenol-like substances, and can be used for
pharmaceutical purposes.
My foreign correspondents, acting on behalf of Professor Dr. A. Classen, the
inventor, now communicate, that new iodine compounds also suitable for pharma-
ceutical purposes can be obtained on treating in a suitable manner with iodine, or
substances capable of yielding iodine, either the hydroxy derivatives of triphenyl-
methane, or derivatives thereof (such as aurine, rosolic acid, phenolphthalein), or
secondary aromatic amines or derivatives thereof, such as diphenylamine, carbazol,
or the like.
According to the researches of Professor Dr. A. Classen, the hydroxytriphenyl-
methane and its analogues can be readily converted into iodine derivatives by
dissolving them in alkalies, adding iodine, and subsequently precipitating the iodine
derivatives with acids.
The iodine derivatives thus obtained differ from the iodine derivatives of hydroxy
compounds hitherto produced, as they are strongly acid in character, readily
dissolving in alkalies, and which is of special value, being capable of forming salts
that can be isolated with readiness.
The acid nature of these new iodine derivatives is due to the fact that all the
iodine atoms enter into the benzene-nuclei or the like, the hydrogen atoms of the
hydroxyl groups remaining unsubstituted by iodine, so that the said iodine compounds
still contain the hydroxyl groups present in the original substances. That this is
the case follows from the solubility of the products in alkalies, from the determination
by titration of their hydroxyl groups, and from their capability of forming aceto
compounds when treated with such acetylating agents as are capable of substituting
the acetyl group for the hydrogen atoms of the hydroxy groups. In particular, it
has been shewn that the iodine derivatives of rosolic acid and auriue are converted
by boiling during several hours with acetic anhydride into the corresponding
triacetyl derivatives, which are reconverted by boiling with soda lye into the
original iodine compounds, whereas the action of acetic anhydride on halogenoxyl
compounds proceeds in an altogether different manner, the iodine contained in the
hydroxyl group being either separated, an acetyl derivative containing corre-
spondingly fewer iodine atoms being formed, or transposed from the hydroxyl group
into the nucleus.
The new iodine compounds are quite odourless, and my foreign correspondents
propose to use them and their salts for pharmaceutical purposes.
The iodine can be used either as sucli, dissolved in a solution of potassium iodide,
or in any other suitable solvent, or it may be used in the form of iodides together
with agents capable of liberating iodine (for instance, chloride of lime, chlorine,
bromine, or the like). According to the researches of the inventor, the electric
current can also be advantageously used in liberating iodine from the iodides.
Iodine chloride, or the combination of iodine chloride and muriatic acid, or the
like agents, can be used in place of iodine, in producing the iodine derivatives from
the said hydroxy products or secondary amines, or the like.

page_text: PRODUCTION OF AURINE TRIIODIDE (OR TRIIODOAURINE) BY THE AID OF
THE ELECTRIC CURRENT.
10 parts of aurine are dissolved in a solution containing 20 parts of sodium
hydroxide, 40 parts of potassium iodide, and 100 parts of water. The liquid thus
formed is subjected, during several hours, to electrolysis, using, for instance, an
electric current of 1-5 ampères per square decimeter of electrode surface, The
iodine compound, which is precipitated by acidulating, is isolated in the manner
described in the foregoing Example A.
PRODUCTION OF TRIIODO ROSOLIC ACID (OR TRIIODIDE OF ROSOLIC ACID)
FROM ROSOLIC ACID, IODINE, AND POTASSIUM IODIDE.
30 parts of rosolic acid are dissolved in a solution prepared from 150 parts of
water and 36 parts of sodium hydroxide, and the liquid is heated on the water bath,
and mixed with a solution prepared from 76 parts of iodine, 80 parts of potassium
iodide, and 600 parts of water. The clear dark-red solution is heated during half
an hour on the waterbath. After cooling the triiodide is precipitated in the form
of red flakes by adding muriatic acid. It is filtered off, redissolved in soda lye, &
again precipitated with muriatic acid. It may be further purified by dissolving it
in chloroform, and separating by means of ligroin. The triiodide thus obtained
forms red flakes.
Triiodo rosolic acid easily dissolves in the usual organic solvents (except ligroin)
at high temperatures, but is less soluble in the said solvents at ordinary temperatures.
It is insoluble in water and acids, but readily dissolves in alkalies. It forms salts
with readiness, and is entirely free from odour. When exposed to moist air or
light, it is not decomposed. Iodine is liberated on heating it alone or with acids.
Its formula is CH₁₂O. (Calculated 55-8 per cent. of iodine; found 56.10 and
55-80 per cent. of iodine.)

page_text: Triiodo rosolic acid can also be produced by the process illustrated by the
Example B, the corresponding quantity of rosolic acid being substituted for the
aurine. In this case, the alkaline solution is with advantage slightly heated during
electrolysis.
Phenolphthalein, when treated in an alkaline solution with iodine and potassium
iodide, is converted into different products, according as the process is carried out
at low or at elevated temperatures. The products thus formed however, are allied,
and can be transformed into one another, as will be evident from the following.
CONVERSION OF PHENOLPHTHALËIN INTO TETRAIODOPHENOLPHTHALËIN
(PHENOLPHTHALËIN TETRAIODIDE) AT LOW TEMPERATURE.
30 parts of phenolphthalein (the parts are by weight) are dissolved in a solution
containing 100 parts of water and 40 parts of sodium hydroxide. This liquid is
mixed with a solution prepared by dissolving 100 parts of iodine and 120 parts of
potassium iodide in 400 parts of water, care being taken that the temperature does
not exceed 20 degrees Centigrade. The original red color of the alkaline solution
of phenolphthalein turns into deep blue. The liquid is then cooled, and subse-
quently acidulated with cold muriatic acid. An amorphous yellowish-brown
substance is precipitated, which is purified by thoroughly washing it with an
aqueous solution of potassium iodide and with water.
The moist precipitate thus obtained, when heated at elevated temperatures (say,
at about 100 degrees Centigrade), is converted into a white substance, which is
tetraiodophenolphthalein, whilst the aforesaid brownish product produced at low
temperature, is a combination of equal molecular proportions of tetraiodophenol-
phthalein and water. The said yellowish-brown product is purified by dissolving
the moist precipitate in chloroform, and separating again with the aid of ligroin.
When subsequently dried in vacuo, it becomes a yellowish powder, entirely free
from odour, and perfectly stable when exposed to air or light. It possesses the
formula: CH100+ H₂O. (Calculated: 60.04 per cent. of iodine; found
60.05 per cent. of iodine.) Its solubility and its other properties agree with these
of the white tetraiodophenolphthalein, which can be at once obtained by operating
at elevated temperatures, for instance, by means of the process illustrated by the
following Example E.
20
PRODUCTION OF WHITE TETRAIODOPHENOLPHTHALEIN AT ELEVATED
TEMPERATURE.
If, in the process illustrated by the preceding Example D, after adding iodine, the
deep-blue coloured solution is heated for some time by means of a steam bath, the
deep blue colour changes into yellowish-brown. On subsequently adding muriatic
acid, a greyish-white substance is precipitated, which is purified by thoroughly
washing with water, or by dissolving it in soda-lye, and precipitating with acids.
The tetraiodophenolphthalein thus obtained is a white powder.
10 4
It is therefore to be supposed, that the lactone ring is opened during the pro-
duction of the aforesaid yellowish tetraiodophenolphthalein, which has the
formula CHO+ H₂O. This yellowish product can
be converted into
the white iodine derivative, and, inversely, the former can be obtained from the
latter. For instance, if the white product is dissolved in cold soda lye, and this
alkaline solution is carefully cooled, and then acidulated with muriatic acid, the
yellow compound represented by the last mentioned formula is precipitated.
The white product, however, is obtained on heating the alkaline solution until the
colour has changed, and subsequently acidulating by means of muriatic acid.

page_text: The white tetraiodophenolphthalein is insoluble in water and ligroin. It easily
dissolves in the other usual organic solvents at elevated temperature, but with less
readiness at low temperature. It is dissolved with the greatest readiness by hot
chloroform. It is insoluble in acids, readily soluble in alkalies. It is also capable
of forming salts, and is free from smell, and stable when exposed to moist air or
light. Analysis shews that it is to be represented by the formula C₂HO
(Calculated 61-77 per cent. of iodine; 29-21 per cent. of -carbon; and 1.22 per cent.
of hydrogen; found 61.92 per cent. of iodine 29-23 per cent. of carbon, and
1.53 per cent. of hydrogen.)
A solution prepared by dissolving 140 parts of potassium iodide in 200 parts of
water is added to a solution containing 30 parts of phenolphthalein, 35 parts
of sodium hydroxide, and 100 parts of water, and the mixture is subjected during
several hours to the action of an electric current of 1.5 ampères per square
decimeter of electrode surface. The end of the action may be distinguished by
the change in colour. The liquid is heated until the blue colour has changed
into brownish-yellow, and the tetraiodophenolphthalein is then precipitated with
muriatic acid.
In producing the iodine derivatives hereinbefore defined, my foreign corre-
spondents do not limit themselves to the directions above given, as these can be
varied, and, generally, all known methods suitable for similar purposes can be
used. For instance, instead of the iodine and potassium iodide prescribed in the
foregoing examples, other suitable agents pro lucing the same result can be used,
such as iodine chloride, or the combination of iodine chloride with muriatic acid
or the like. Potash-lye, ammonia-liquor, or the like, or solutions of certain salts
(such as borates biborates, phosphates, or pyrophosphates, or the like) can be used
as solvents for the hydroxy compounds to be iodised. These last named salts,
especially the alkaline borates, biborates, phosphates, and pyrophosphates, form
soluble alkaline salts with phenolphthalein or the like. On adding thereto either a
solution of iodine in a solution of potassium iodide, or in any other suitable solvent,
or a solution containing iodides (such as potassium iodide), or iodic acids, together
with an agent capable of liberating the iodine, the formation of the new iodine
compounds proceeds in such a manner that the acids contained in the above named
borates, or the like, are liberated by the action of the free iodine, a perceptible
acid action being developed, the new iodine compounds at once separating from
the acid liquid. The iodine compounds are thus at once formed in so pure a
state, that after treatment with steam, for example, they can be obtained in a
pure state.
This manner of working has been found to be advantageous, especially when
the process is to be carried out on a large scale.
The following example will serve to illustrate this mode of working. The parts
are by weight.
EXAMPLE G.
PRODUCTION OF TETRAIODOPHTHALËIN
FROM PHENOLPHTHALËIN IN THE
PRESENCE OF BORAX.
20 parts of phenolphthalein are dissolved, with the aid of beat, in 500 parts of
water containing 80 parts of borax; this liquid is kept hot, and mixed with a
solution prepared either by dissolving 90 parts of iodine in 500 parts of an aqueous
solution containing 100 parts of potassium iodide (or the corresponding quantity
of any other solvent for iodine), or by dissolving the equivalent quantity of iodine

page_text: salts in a medium that will liberate the iodine (such as chlorine, bromine, chloride
of lime, or the like). The original blue colour of the solution, which is at first
alkaline, gradually changes into a yellow, 'the tetraiodo-compound separating at
the same time from the liquid, which gradually becomes acid. The action is
complete when the liquid shews the permanent colour of iodine. The precipitate
is filtered off, and freed by means of a current of steam from any remaining iodine.
It is then pure, and is identical with the white tetraiodophenolphthalein herein-
before referred to.
This example is typical of the method of preparing the new iodine compounds
with the aid of borates, biborates, phosphates, pyrophosphates, or the like.
Naturally, certain modifications can be applied. Thus, for instance, the aqueous
borax solution, or the like, can be allowed to flow slowly into the solution
prepared by dissolving iodine in potassium iodide or the like, the same result being
thus obtained.
The iodine compounds obtainable as illustrated by the foregoing examples, are
excellent substitutes for iodoform in the treatment of wounds. They are absolutely
innocuous (whether used externally or internally), and not at all irritating.
Their solubility in weak alkalies also renders such substances capable of extended
application for pharmaceutical purposes.
As above mentioned, the iodine compounds hereinbefore defined are capable of
forming salts, which can readily be separated.
The production of these salts may be illustrated by some particulars relating to
the preparation of the salts of tetraiodophenolphthalein.
The salts of tetraiodophenolphthalein can be obtained from the aforesaid yellowish
or white tetraiodide.
The sodium salt of phenolphthalein-tetraiodide is obtained, for instance, by
dissolving tetraiodophenolphthalein in the calculated quantity of soda lye, and
subsequently evaporating the liquid to dryness. This sodium salt has the
formula:-
The zinc salt is produced by the interaction of equivalent quantities of the
aforesaid sodium salt and zinc chloride in a watery solution. It forms a brown
flocculent precipitate.
In order to prepare the ferrous & ferric salt of tetraiodophenolphthalein, equivalent
quantities of iron, alum, or ferric sulphate, and of the above-mentioned sodium salt,
are mixed in aqueous solution.
By the interaction of equivalent quantities of alum, mercuric chloride, or
bismuth trichloride, & the said sodium salt in a watery solution, the aluminium,
mercuric, & bisinuth salts are obtained in a similar manner. Of the last named
agents, mercuric chloride & bismuth trichloride are, with advantage, used, dissolved
in five times their quantity of a saturated solution in water of common salt.
The mercuric salt, which is a brown flocculent precipitate, has the formula :-

page_text: The bismuth salt forms brown flakes, and is represented by the following
formula :-
--
The other salts have an analogous composition.
In order to produce these salts, the solution of the sodium salt is advantageously
allowed to flow into the solution of the metallic salts, until the liquid above the
precipitates assumes a slightly blue colour. The precipitates are then filtered off,
& purified in a suitable manner, for instance, by treating with steam, and thoroughly
washing out.
It has been ascertained that in the formation of the salts hereinbefore defined,
the tetraiodophenolphthalein behaves as a bibasic acid, as the two hydrogen atoms
of the two hydroxyl groups are always displaced by an equivalent quantity of
metal.
All these salts, and the analogous salts derived from the other iodine compounds
hereinbefore defined, are perfectly odorless, and are unaffected by light and
moisture. They are suitable for use for pharmaceutical purposes, and the sodium
salt can be used, either as such, or in solution, for these purposes.
In order to produce salts of the iodine compounds herein before defined, my
foreign correspondents do not limit themselves to the particulars above given, as
these can be varied.
The production of the salts of the iodine derivatives can be effected by means of
all methods known and in use for analogous or similar purposes.
New iodine compounds can be prepared by allowing iodine to act (in the presence
of an agent capable of decomposing or absorbing the hydroiodic acid formed during
the process) ou secondary aromatic amines, or derivatives thereof, such as
diphenylamine, carbazol, or the like. The iodine derivatives thus obtainable are
distinguished by their strong antiseptic properties, and possess, as compared with
other iodine preparations, the advantage of complete absence of odour. They can
also be obtained with the greatest readiness in a crystallized form. These iodine
derivatives are also suitable for pharmaceutical purposes, that is to say, as
substitutes for iodoform and the like.
Experiments have shown that, for instance, mercuric oxide may be, with
advantage, used as an absorbent of the hydriodic acid formed during the action of
iodine on the secondary amido compounds, but other agents can also be used,
provided they are able either to combine with the bydriodic acid, or to decompose
this acid.
These last mentioned iodine compounds, obtained from secondary aromatic amines,
or derivatives thereof, can be readily converted, either into acid derivatives, by
treatment with suitable agents (such as acid chlorides, acid anhydrides, or the like),
or into nitroso derivatives (by treatment with nitrous acid or the like), products
being thus obtained which likewise possess antiseptic properties.
The production of these iodine compounds, derived from secondary aromatic
amines, or derivatives thereof, is illustrated by the following two examples, the
parts being by weight.

page_text: kilos. by weight), is heated to the boiling point, during three hours, in a vessel
provided with a reflux condenser. The boiling liquid is filtered, and the filtrate is
poured in 2000 litres of cold water, in which 200 parts of potassium iodide have
been dissolved, in order to prevent a precipitation of the mercuric iodide. A light
yellow product separates, which is filtered-off, and washed with warm water, until
the washings no longer contain iodine or mercury. The iodine derivative is thus
obtained in a pure state, as an amorphous mass. When crystallised from hot alcohol,
or hot glacial acetic acid, it forms yellow laminæ, melting at 184 degrees
Centigrade.
The carbazol diiodide (diiodo-carbazol) thus formed, is insoluble in water, easily
soluble in benzene, ether, hot alcohol, chloroform, and glacial acetic acid. Iodine
is liberated when it is heated alone, or with sulphuric or nitric acid. It is
perfectly free from odour, and is not altered at ordinary temperature by alkalies
or acids.
It possesses the formula :-
PRODUCTION OF diiododiphenYLAMINE (DIPHENYLAMINE DIIodide).
A mixture containing 50 parts of diphenylamine, 200 parts of mercuric oxide,
250 parts of iodine, and 2000 litres (in case the parts are kilos. by weight) of
alcohol, is heated to boiling, during two hours, in a vessel provided with a reflux
condenser. The liquid is then filtered, and the filtrate thus obtained is at once
mixed with a solution prepared by dissolving 200 parts of potassium iodide in
water. The dark-grey colored crystalline precipitate which separates is filtered
-off, dissolved in alcohol, and treated with animal charcoal. On adding water to
the filtered alcoholic solution, the iodine derivative is precipitated in the form of
highly lustrous lamina, which become clear and transparent as glass, after repeated
treatment with animal charcoal in alcoholic solution, and subsequently precipitating
with water. This iodine compound melts at 129 degrees Centigrade.
Diphenylamine diodide (or diiododiphenylamine) thus produced is insoluble in
water, easily soluble in the usual organic solvents. It is not affected by dilute
-acids and alkalies. When boiled with sulphuric or nitric acid, or when heated in
a capillary tube at 200 degrees Centigrade, it gives off iodine. It is quite odourless,
.not poisonous, and possesses strong antiseptic properties. Its formula is :--
(Calculated 60-24 per cent. of iodine and 3.33 per cent. of nitrogen; found
60-4 per cent. of iodine and 3.45 per cent. of nitrogen.)
Similar iodine compounds are obtained if, in the processes illustrated by the
foregoing Examples H and K, other secondary aromatic amines, or derivatives
thereof, be used in place of diphenylamine or carbazol. These iodine derivatives,
in general, show properties similar to those of the last-named two iodine products,
viz.-diiododiphenylamine and diiodo carbazol.
As above mentioned, the iodine derivatives obtained from secondary aromatic
-amines, or derivatives thereof, can easily be converted into acid and nitroso

page_text: derivatives which also possess antiseptic properties. The production of these
derivatives is illustrated by the following Examples L and M. The parts are by
weight.
CONVERSION OF
EXAMPLE L.
DIODODIPHENYLAMINE
INTO NITROSO DIIODO-
DIPHENYLAMINE.
30 parts of diphenylamine diiodide are dissolved in 500 parts of absolute alcohol,
and 60 litres (in case the parts are kilos. by weight) of fuming muriatic acid
(specific gravity 1.19) are then added. After cooling this with ice, it is slowly
mixed with a cooled solution prepared by dissolving 60 parts of sodium nitrite in
100 parts of water. The nitroso compound which at once separates, is filtered off,
after adding a small quantity of ice water, and washed with a small quantity of alcohol.
It is then redissolved in absolute alcohol, and this solution is then treated with
animal charcoal. From the filtered alcoholic solution, the nitroso compound is
deposited, on cooling, in long, fine, yellow laminæ, melting at from 119 to
120 degrees Centigrade.
It is easily soluble in ordinary hot organic solvents, less readily at ordinary
temperatures. It is insoluble in water, and becomes decomposed when treated with
strong acids, or when heated on platinum,-nitrous acid and iodine being liberated.
It is absolutely odourless, and has the following formula :—
PRODUCTION OF ACETO-DIIODO DIPHENYLAMINE.
30 parts of diphenylamine diiodide are dissolved in benzene, and after adding a
small excess of acetyl chloride, the mixture is boiled, during about 6 hours, in a
vessel provided with a reflux condenser, until hydrochloric gas is no longer dis-
engaged. The clear solution is then evaporated, in order to remove the benzene,
and the residue is digested with warm water, in order to decompose the acetyl-
chloride in excess. The acetyl derivative is extracted from the product by means
of a considerable quantity of ether. On evaporating the ethereal solution, a
residue, consisting of the acetyl derivative, remains, which is dissolved in dilute
alcohol, and the alcoholic solution is then treated with animal charcoal, and the
filtered solution is allowed to evaporate. The acetyl derivative deposits in
beautiful brilliant colorless laminæ, melting at 138 degrees Centigrade. It is very
readily soluble at elevated temperatures in the usual organic solvents, and less
readily at ordinary temperatures. It is decomposed, when boiled with strong acids,
or when heated on platinum, iodine being disengaged. It is also perfectly odourless,.
and possesses the formula :-

page_text: The benzoyl derivative of diphenylamine diiodide is obtained in a manner
analogous to that herein before described in the case of the acetodiphenylamine
diiodide, but the excess of benzoyl chloride is decomposed by using hot soda-lye,
in order to keep the benzoic acid dissolved. The benzoyldiphenylamine diodide is
filtered off and crystallized from dilute alcohol. It forms colourless lamina
melting at from 156 to 157 degrees Centigrade, and possesses properties similar
to those of the above-described acetyl derivative. It is also perfectly odourless,
and possesses the formula:
My foreign correspondents have described in the preceding Examples H and K,
several distinct methods of practically producing from secondary aromatic amines,
or derivatives thereof, some of the iodine compounds herein before referred to.
Naturally, they do not limit themselves to the directions given, as these can be
varied. For instance, iodides such as potassium iodide or the like, and other
agents capable of liberating iodine, can be used in place of free iodine used in the
last-named example. The combination of iodine chloride and muriatic acid, or
similar agents, can also be used, in order to prepare the last defined iodine products,
iodine compounds being thus obtained which, when treated in a suitable manner
with acid chlorides, or acid anhydrides, are transformed into acid derivatives, and
when treated with nitrous acid or the like, they are converted into nitroso products.
These acid derivatives and nitroso compounds possess technical value, as they can
be used as antiseptics in the same manner as the original iodine derivatives
herein before defined.
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 is :-
. 1. The process for producing iodine derivatives containing the iodine in the
aromatic nuclei from hydroxytriphenylmethane, or derivatives thereof, which
process consists :-
(a) In acting with iodine, iodine chloride, iodine chloride hydrochloric acid, or
other analogous iodising agents, either on alkaline solutions of hydroxytri-
phenylmethane, or derivatives thereof, or on solutions of hydroxytriphenyl-
methane, or derivatives thereof, in an alkaline borate, biborate, phosphate,
pyrophosphate, or the like; or
(b) In treating alkaline solutions of hydroxytriphenylmethane, or derivatives
thereof, with alkaline iodides in the presence of suitable agents capable
of liberating iodine from iodides (such as chlorine, bromine, chloride of
lime, or the like); or
(c) In allowing the electric current to act on alkaline solutions of hydroxytri-
phenylmethane, or derivatives thereof, to which solutions alkaline iodides
are added;
And in finally precipitating, by means of acids, the free iodine derivatives, in case
the resulting liquids shew an alkaline solution.
2. The production of triiodoaurine, triiodorosolic acid, and tetraiodophenol-
phthalein, from aurine, rosolic acid, and phenolphthalein, according to the process.
defined in the foregoing claim.
3. The conversion of the hereinbefore defined iodine derivatives of hydroxytri-
phenylmethane, or derivatives thereof (such as tri iodo-aurine, triiodorosolic acid,
tetraiodophenolphthalein), into salts, by substituting, in any suitable manner,

page_text: alkaline or heavy metals for the hydrogen atoms contained in the hydroxyl
groups of the said iodine compounds of hydroxytriphenylmethane, or derivatives
thereof.
4. The process for producing iodine derivatives containing iodine in the aromatic
nuclei from secondary aromatic amines, or derivatives thereof (such as diphenylamine,.
carbazol, or the like), which process consists in allowing iodine to act in the
presence of suitable agents, capable of absorbing or decomposing the hydriodic
acid, on solutions of secondary aromatic amines, or derivatives thereof.
5. The production of diiododiphenylamine and diiodocarbazol from diphenyl-
amine and carbazol, by means of the process defined in the preceding fourth
claim.
6. The conversion of the iodine derivatives obtainable from secondary aromatic
amines, or derivatives thereof (such as diiododiphenylamine, diiodo carbazol),
into new iodine compounds, by substituting for the hydrogen atom of the imido.
group, the nitroso acetyl or benzoyl group, or the like, which process consists in
treating the said iodine derivatives with nitrous acid or the like, or with acid
anhydrides or acid chlorides, or a mixture thereof, or other agents acting in the
same or a similar manner.
7. The production of nitroso diiododiphenylamine, acetyl diiododiphenylamine,.
benzoyldiiododiphenylamine, from diiododiphenylamine, by means of the process
defined in the preceding sixth claim.
8. As new products of manufacture, the new iodine derivatives, salts and other
derivatives thereof, such as triiodo aurine, triiodorosolic acid, tetra iodophenol-
phthalein, and salts thereof, containing alkaline or heavy metals, in place of the
hydrogen of the hydroxyl groups; diiododiphenylamine, diiodo carbazol, nitroso
diiododiphenylamine, acetyl diiododiphenylamine, benzoyldiiododiphenylamine,
or the like, produced by the processes hereinbefore defined, or by any other
process affording the same result.
9. The use of the hereinbefore defined iodine derivatives, salts and other
derivatives thereof, for pharmaceutical purposes.
Dated this 4th day of April 1895.
NEWTON & SON,
Agents for the Applicant.