The Manufacture of Iodine Compounds from Phenols or Carboxylic Acids thereof.
Year: 1892

page_text: Date of Application, 8th Sept.; 1892
Complete Specification Left, 8th June, 1893-Accepted, 22nd July, 1893
PROVISIONAL SPECIFICATION.
[Communicated from abroad by THE FARBENFABRIKEN vormals FRIEDRICH
BAYER & Co., of Elberfeld, in the Empire of Germany.]
The Manufacture of Iodine Compounds from Phenols or Carboxylic
Acids thereof.
I HENRY EDWARD NEWTON of The Office for Patents, 6 Breams Buildings,
Chancery Lane in the County of London, Patent Agent, do hereby declare the
ature of this invention to be as follows:-
In the Specifications of Letters Patent granted to Benjamin Willcox, viz.,
No. 5079, dated 23rd March 1889, No. 18021, dated 8th November 1890, and
No. 7026, dated 23rd April 1891, for inventions communicated to the said
Benjamin Willcox by my present correspondents, the production of new iodine
It is noticeable
derivatives of phenols and carboxylic acids thereof is described.
that these iodine compounds contain iodine in place of hydrogen of the hydroxylic
group; are of an amorphous nature; and are more or less coloured. For instance,
in the Specification of the above named Letters Patent No. 5079, the iodine
products obtained from phenol, salicylic acid, cresol carboxylic acid, and the methods
for producing them, are described.
My foreign correspondents have further found that in treating with iodine and
alkalies, phenols or carboxylic acids thereof, under modified conditions stated by
them, another series of iodine products results, which differ from the iodine
compounds described in the aforesaid three Letters Patent, by their capability of
crystallising, by their being colourless and inodorous, and by their exhibiting
peculiar properties in the presence of alkalies. This new method consists in
employing alkalies or alkali carbonates, not in excess, but in certain accurately
calculated or definite quantities, and in a considerably diluted state. By means of
this process, which is of general application, a very great number of iodine
compounds is obtained by my foreign correspondents.
In order to illustrate the method for producing these substances, the following
example is given, the parts being by weight:
:-
1-52 parts of orthohydroxyparatoluylic acid are dissolved in 1500 parts of water
with the addition of 1-06 parts of sodium carbonate, and a solution prepared by
dissolving 7.62 parts of iodine and 7.62 parts of potash iodide in about 30 parts of
water, are slowly added. After about 24 hours, the new iodine product, formed in
When crystallized out of
this way and separating perfectly, is filtered off.
benzene, ligroine, or alcohol, it melts at 121-5 degrees centigrade.
The
Of course, the manufacture of this product and analogous substances is not
restricted to the proportions above enumerated, for they can be varied.
quantity of iodine, for instance, can be diminished, employing in place of 6 atoms
used in the said example, only 4 atoms, and in place of iodine, as such, it may be
employed with the same result in the nascent state, that is, liberated from. iodides
by means of chlorine, bromine, hypochlorites or other substances capable of
producing the same effect. The sodium carbonate, which must be used in the
quantity corresponding to one molecular proportion for one molecular proportion
of a phenol or the like, can be replaced by the equivalent quantity of other alkali
carbonates, or by such a quantity of alkalies as corresponds to two molecular
proportions.
The new substance produced in the manner hereinbefore described possesses the
following formula: CHI,CH,(OH), as my foreign correspondents have
ascertained by analytical research. It results from the orthohydroxy paratoluglie
acid (meta-cresotinic acid) employed by separation of carbon dioxide out of the

page_text: carboxylic group, and substitution
of the benzene nucleus.
J
three iodine atoms for three hydrogen atoms
The reaction taking place under the conditions aboye defined, viz., in, subjecting
meta-cresotinic acid to this process, can be illustrated by the following equation
I
of the benzene nucleus.'.
N
The reaction taking place under the conditions aboye defined, viz., in, subjecting
meta-cresotinic acid to this process, can be illustrated by the following equation:-
-
CH3
CH, OH + Na,CO₁ + 61 = CHI,
соон
+ 2 NaI + HI+ H₂O + 2CO.
OH
·
As the new product thus obtained, which represents a cresoltrisiodide, easily
dissolves in diluted alkaline lye, it is ascertained that it contains still a free
hydroxylic group. By treating with reducing agents, it yields meta-cresol. This
dodine product dissolves in alcohol and ligroine with difficulty, but easily in ether,
benzene, chloroform, and in fatty oils. It could not be obtained by treating meta-
cresol with iodine.
In an analogous manner as herein before described, the process proceeds in the
employment of the isomeric, ortho-, and para cresotinic acid, cresoltrisiodides being
formed, which in general are similar to the isomeric product obtained from meta
cresotinic acid. Amongst the hydroxybenzoic acids, for instance, salicylic acid
yields phenol trisiodide, melting at 156 degrees centigrade. If phenol, analogues
or homologues thereof, naphthol, and the like, are employed, similar substances
result by means of the aforesaid process, viz., by employing one molecular propor-
tion of phenol etc., and either one molecular proportion of alkaline carbonate, or two
molecular proportions of alkaline hydrate, and the necessary quantity of iodine,
effecting these operations as hereinbefore defined.
The cresoltrisiodides and the analogous substances thus produced, differ totally
in their physical and chemical properties from those iodides which, are described in
the Specifications of the aforesaid three Letters Patent.
My foreign correspondents have further found that the new products above
defined are capable of employment for pharmaceutical purposes other than those
to which the former products were applicable, as these new substances have been
found to be effective for the treatment of diseases in which no result could be
obtained by means of the products described in the Specifications of the said three
Letters Patent.
The characteristic difference between the latter compounds & these new substances,
consists in that the above defined iodides contain a free hydroxylic group, & do
"not represent iodine oxygen products containing the group IO→ bound to the
benzene nucleus or the like.
1.
::..
:
"
i
COMPLETE SPECIFICATION.
The Manufacture of Iodine Compounds from Phenols or Carboxylic
Acids thereof.
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:-
In the Specifications of Letters Patent granted to Benjamin Willcox, viz.,
**No. 5079, dated 23rd March 1889; No. 18021, dated 8 November .1890; and
No. 7026, dated 23rd April 1891, for inventions communicated to the said
Benjamin.Willcox by. my present: correspondents, the production of new iodine
derivatives of phenols and carboxylic acids thereof is described. It is noticeable

page_text: that these iodine compounds containing iodine in place of the hydrogen of the
hydroxylic group, are of an amorphous nature, and are more or less colored.
For instance, in the Specification of the above named Letters Patent No. 507989,
the iodine derivatives obtained from phenol, salicylic acid, cresol carboxylic acid,
and the methods for producing them, are described.
My foreign correspondents have further found, that on treating phenols, or
carboxylic acids thereof, with iodine and alkalies, under certain modified conditions,
another series of iodine derivatives are formed, which differ from those described
in the aforesaid three Letters Patent by their capability of crystallising, by
being colorless and inodorous, and by exhibiting peculiar properties in the presence
of alkalies. This new method consists in employing alkalies or alkali carbonates
not in excess, but in certain accurately calculated or definite quantities, and in
a considerably diluted state. By means of this process, which is of general
application, a very great number of iodine derivatives is obtained by my foreign
correspondents.
In order to illustrate the method of producing these substances, the following
example is given, the parts being by weight.
152 parts of orthohydroxy paratoluic (metacresotinic acid) acid, are dissolved in
1500 parts of water, together with 1-06 parts of sodium carbonate, and a solution
prepared by dissolving 7.62 parts of iodine, and 7.62 parts of potassium iodide, in
about 30 parts of water, is slowly added. After about 24 hours, the resulting new
iodine derivative, which separates perfectly, is filtered off. When crystallised
from benzene, ligroin, or alcohol, it melts at 121.5 degrees centigrade.
The manufacture of this product and analogous substances, is not restricted to
the directions above given, as they can be varied. For instance, in place of using
iodine, as such, it may be employed with the same result at the moment of liberation
from iodides by means of chlorine, bromine, hypochlorites, or other substances
capable of producing the same effect. The sodium carbonate, which must be used
in proportions corresponding to one molecular proportion for one molecular propor-
tion of a phenol, or the like, can be replaced by the equivalent quantity of other
alkali carbonates, or of alkalies.
The new substance produced in the manner hereinbefore described,
possesses the
following formula :-CHI,CH,-(OH)-which my foreign correspondents have
ascertained by analytical research. It is formed from the orthohydroxyparatoluic
acid (metacresotinic acid) employed, by the separation of carbon dioxide from the
carboxylic group, and simultaneous substitution of three iodine atoms for three
hydrogen atoms of the benzene nucleus.
The action taking place under the conditions above, defined, viz., on subjecting
metacresotinic acid to this process, is illustrated by the following equation
contains the hydroxylic group.
It dissolves
On treatment with reducing agents, it is reconverted into metacresol.
in alcohol and ligroin with difficulty, but easily in ether, benzene, chloroform, and
in fatty oils. It cannot be obtained by treating metacresol with iodine.
The process may be applied in an analogous manner, as hereinbefore described,
to the isomeric ortho and paracresotinic acid, triiodo derivatives of cresol being
formed which in general are similar to the isomeric product obtained from meta-
cresotinic acid. The triiodide from orthocresotinic acid melts at 60.5 degrees
0 centigrade, whilst the triiodide from paracresotinic acid melts at 57 degrees
centigrade. Both compounds are easily soluble in alcohol, ether, benzene, .

page_text: chloroform, and fatty oils. Salicylic acid yields triiodophenol, melting at
.156 degrees centigrade. If phenol, analogues or homologues thereof, naphthol,
and the like, are employed, similar substances are obtained by means of the afore-
said process, viz., by employing one molecular proportion of phenol, or the like, and
either one molecular proportion of alkali carbonate, or two molecular proportions
of alkali hydrate, and the necessary quantity of iodine, the operations being carried
out as hereinbefore defined.
The iodine derivatives thus produced differ totally in their physical and chemical
properties from the iodides which are described in the Specifications of the
aforesaid three Letters Patent.
My foreign correspondents have further found that the new products above
defined, may be used for pharmaceutical purposes other than those to which the
former products were applicable, as these new substances have been found to be
effective in the treatment of diseases which were unaffected by the products
described in the Specifications of the said three Letters Patent.
The characteristic difference between the latter compounds and these new sub-
stances, consists in that the above defined iodides contain a hydroxylic group, and
are not. oxy indo derivatives containing the group 10 → bound to the benzene
nucleus, or the like.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed, as communicated to me,
I declare that what I claim is :-
:-
1. The production of iodine derivatives by treating phenols, or carboxylic acids
thereof, with iodine, in presence of alkalies, substantially as hereinbefore described.
2: The process of producing triiodocresols, which consists in treating one
molecular proportion of orthocresotinic acid (CH: OH: COOH- 1.: 2.: 3),
metacresotinic acid (CH₂: OH: COOH = 1: 3: 4), or paracresotinic acid
(CH, OH: COOH = 1:4: 5), dissolved in a suitable solvent with one molecular
proportion of an alkaline carbonate, or two molecular proportions of an alkaline
hydroxide, and with three molecular proportions of iodine, or the corresponding
quantity of alkaline iodide (in the latter case, in the presence of such agents as are
capable of liberating iodine from the alkaline iodide employed).
-
3. As new products of manufacture, the triiodocresols obtainable as hereinbefore
described, or by any other way, and having the properties herein before mentioned.
4. The employment of the triiodocresols, especially that which results from
metacresotinic acid, for therapeutic purposes.
Dated this 8th day of June 1893.
NEWTON & SON,
Agents for the Applicant.