Improvements in the Manufacture of Iodine Substitution Products of Phenols and Cresols.
Year: 1891

page_text: Date of Application, 23rd Apr., 1891
Complete Specification Left, 19th Jan., 1892-Accepted, 20th Feb., 1892
PROVISIONAL SPECIFICATION.
Improvements in the Manufacture of Iodine Substitution Products
of Phenols and Cresols.
I BENJAMIN WILLCOX of 47 Lincoln's Inn Fields in the County of Middlesex
Patent Agent do hereby declare the nature of this invention which invention
has been communicated to me from abroad by Farbenfabriken vormals Friedrich
Bayer & Co. of Elberfeld in the Empire of Germany, to be as follows:-
By the action of iodine in the presence of alkali upon certain phenols my foreign
correspondents have succeeded in obtaining peculiar iodine substitution products of
these substances in which the hydroxyl hydrogen atom is replaced by iodine which
products are already largely in demand for medicinal purposes. Products of this
class have been described in the Specifications accompanying applications for
Letters Patent No. 5079 of 1889 and 18021 of 1890 as being obtained from phenol
cresol, thymol, para-isobutyl-phenol, para-isobutyl, ortho- and meta-cresol etcetera
etcetera.
My foreign correspondents have now discovered that other mono- and di-alkyl
substituted phenols such as the ethyl, propyl- and amyl-phenols, the methyl, ethyl-
and amyl-cresols also the propyl-cresols isomeric to thymol and carvacrol can be
converted into iodine derivatives of the same description.
Of these substituted phenols and cresols the following are known.
First The methyl substituted cresols; the xylenols and the dimethyl substituted
cresols.
Second-The ethyl substituted phenols also an ethyl cresol (obtained from
methyl-ethyl-benzene-sulpho acid by a melting process.
Third The normal propyl-phenols also ortho- and para-iso-propyl-phenol
(cumo-phenols).
Fourth Sundry propyl-cresols, para-propyl ortho-cresol, propyl-meta-cresol,
isopropyl meta-cresol, meta-iso-cymo-phenol.
Fifth-Amyl-phenol from phenol- and amyl-alcohol by heating with chloride
of zinc.
The other as yet unknown substituted cresols are obtained by my foreign
correspondents by heating cresol with suitable alcohols in the presence of chloride
of zinc.
The known substituted cresols hereinbefore specified can also be partly obtained
by means of this process.
The method of conducting the process in the manufacture of iso-amyl-ortho-
cresol is described as an example showing the application of the invention in practice
the parts being by weight.
10-8 parts of ortho-cresol 8.8 parts of iso-amyl-alcohol and 17 parts of chloride of
zinc are heated to 180 degrees centigrade in a vessel provided with an agitating or
stirring apparatus and cooling appliances and the degree of heat applied is then
lowered so that the liquid simmers gently. After a time water will separate and
two layers are formed.
The lower layer consists of a solution of chloride of zinc and the oily upper
layer is for the greater part composed of the iso-amyl-ortho-cresol and unchanged
cresol which are contaminated with higher substituted phenols, ethers, and the like.
After heating for about half an hour the temperature being allowed to rise to about
190 degrees centigrade the materials are allowed to cool and are mixed with water,
some hydrochloric acid is then added and the oil taken off. The latter is shaken
out with diluted soda lye and the phenol in solution is precipitated by the addition of
hydrochloric acid.
By means of fractional distillation the different phenols can then be separated.

page_text: The greater part is composed of the iso-amyl-ortho-cresol which boils at from 255
to 258 degrees centigrade. The same forms a thick colourless oil which does not
solidify even in a cold mixture.
The other methyl-ethyl-propyl-, and amyl- substituted ortho-cresols and meta-
cresols are obtained in like manner.
The process for the production of the iodine derivatives of these substituted
phenols and cresols is explained by the following example (the iodine derivatives of
thymol and carvacrol are excepted).
178 parts (by weight) of iso-amyl-ortho-cresol are dissolved in 178 parts of soda
and 2000 parts of water and mixed with an excess of iodine solution at 0 degrees
centigrade. A yellow precipitate results which is separated by filtration and
purified by washing.
In place of adding the iodine by itself compounds of iodine such as alkaline
iodides may be employed the iodine being set free by means of subchlorous acid
salts chlorine and the like. The iso-amyl-ortho-cresol-iodide forms a yellow powder
melting and decomposing at from about 60 to 70 degrees centigrade.
In an analogous manner the iodine derivatives of the remaining substituted
phenols and cresols are obtained in the form of an amorphous precipitate. The chief
characteristic of these iodoxyl compounds is that they all of them yield, or give
off, iodine when heated to, or above the melting point. They are insoluble in
water but dissolve readily in olive oil, ether, and chloroform; and generally
somewhat less readily in alcohol, benzene, and ligroin.
Dated the 23rd day of April 1891.
J. H. JOHNSON & Co.,
Agents.
COMPLETE SPECIFICATION.
Improvements in the Manufacture of Iodine Substitution Products
of Phenols and Oresols.
I BENJAMIN WILLCOX of 47 Lincoln's Inn Fields in the County of Middlesex
Patent Agent do hereby declare the nature of this invention (which has been
communicated to me from abroad by Farbenfabriken vormals Friedrich Bayer &
Co. of Elberfeld in the Empire of Germany) and in what manner the same
is to be performed to be particularly described and ascertained in and by the
following statement :—
By acting with iodine in the presence of alkali on certain phenols my foreign
correspondents have succeeded in obtaining valuable iodine substitution derivatives
of these substances in which the hydrogen atom of the hydroxyl group is displaced
by iodine. These iodine compounds are already largely in demand for medical
purposes. Such products have been described in the Specifications of Letters
Patent No. 5079 dated 23rd March 1889 and No. 18021 dated 8th November 1890
as being obtained from phenol, cresol, thymol paraisobutylphenol, paraisobutyl-
orthocresol and paraisobutylmetacresol.
My foreign correspondents have now discovered that other homologues of phenol
such as the ethyl, propyl and amyl phenols the methyl, ethyl and amyl cresols also
the propyl cresols which are isomeric with thymol and carvacrol can be converted
into similar iodine derivatives which may likewise be employed as medicines.
Of these substituted phenols and cresols the following have already been
described:
1.) The methyl substituted cresols (xylenols) and the dimethyl substituted
cresols.
2.) The ethyl substituted phenols and the ethyl cresol which has been obtained
by fusing methyl ethyl benzene sulpho acid with alkalies.
3.) The normal propyl phenols, ortho and para iso-propyl phenol (the so-called
cumo phenols).

page_text: 4.) The following propyl cresols, para propylorthocresol, propyl meta cresol,
isopropyl meta cresol, meta iso cymo phenol, and
5.) Amyl phenol obtained by heating phenol amyl alcohol with chloride of zinc.
The hitherto unknown substituted cresols ethyl ortho cresol, normal propyl ortho
cresol, iso amyl ortho cresol and isoamyl meta cresol have been prepared by my
foreign correspondents by heating ortho or meta cresol with the different alcohols
in the presence of chloride of zinc and they have found that several of the above
named known substituted cresols can also be very advantageously prepared by
this process.
The method of conducting the process in the manufacture of iso amyl ortho cresol
is described in the following example shewing the application of the invention in
practice the norte haine he
10-8 parts of ortho cresol and 8.8 parts of iso amyl alcohol and 17 parts of
chloride of zinc are quickly heated to 180 degrees centigrade in a vessel provided
with an agitating or stirring apparatus and condenser. The heat is then lowered so
that the liquid boils gently. After some time owing to the separation of water two
layers are formed the lower of which consists of zinc chloride partly dissolved in
the disengaged water whilst the oily upper fluid in greater part consists of iso
amyl ortho cresol mixed with unaltered cresol and with substituted phenols and ethers
of high moleculary weight which are formed as by-products. After heating for
about half an hour the temperature is raised to about 190 degrees centigrade, then
the mixture is allowed to cool and after the addition of water and a small quantity
of hydrochloric acid the oil is separated from the aqueous solution and extracted
with diluted soda-lye. The dissolved phenols are then separated by the addition of
hydrochloric acid. The several products are separated by fractional distillation
the greater part consisting of the iso-amyl-ortho-cresol which boils constantly at
255 to 258 degrees centigrade. The iso-amyl-ortho cresol thus obtained is a thick
colourless oil which does not solidify even when exposed to a low temperature.
The other methyl, ethyl, propyl and amyl substituted ortho and meta cresols can
also be obtained in the same manner.
The general process for the production of the iodine derivatives of these
substituted phenols and cresols is explained by the following example (the iodine
derivatives of thymol and carvacrol being excluded).
SECOND EXAMPLE.
PRODUCTION OF ISO-AMYL-ORTHO-CRESOL-IODIDE.
178 parts by weight of iso-amyl-ortho-cresol are dissolved in a solution of
178 parts by weight of soda in 2000 parts by weight of water and an aqueous solution
of an excess of iodine in potassium iodide is added thereto at 0 degrees centigrade.
A yellow precipitate results which is separated by filtration and purified by
washing.
In place of adding the iodine by itself iodine compounds such as alkaline iodides
may be employed the iodine being set free by means of hypochlorites, chlorine or
the like.
The resulting iso-amyl-ortho-cresol iodide obtained forms a yellow powder melting
at from about 60 to 70 degrees centigrade with decomposition.
The iodine derivatives of the other substituted phenols and cresols above named
are obtained in the form of amorphous yellowish precipitates by operating in a
similar manner.
All these iodine compounds possess the property of giving off iodine when heated
to or over the melting point. They are insoluble in water, but dissolve readily in

page_text: olive oil, ether and chloroform, and somewhat less readily in alcohol, benzene and
ligroine.
Having now particularly described and ascertained the nature of the said inven-
tion and in what manner the same is to be performed 1 declare that what I
claim is―
1.) The production of ethyl-ortho-cresol, normal propyl-ortho-cresol and iso-amyl-
ortho-cresol by heating ortho-cresol with ethyl-alcohol, normal propyl-alcohol or
iso-amyl alcohol in the presence of zinc chloride and also the manufacture of
iso-amyl-meta-cresol by beating meta-cresol and iso-amyl-alcohol together with zinc
chloride.
2.) The production of iodine compounds containing the iodine in place of the
hydrogen atom of the hydroxyl group from ethyl-phenol, propyl-phenol, amyl
phenol, methyl ortho-cresol, ethyl ortho-cresol propyl-ortho-cresol, amyl-ortho-
cresol, methyl meta cresol, ethyl meta cresol, propyl meta cresol, or amyl meta
cresol by acting on their alkaline solutions with iodine or with alkaline iodides in
the latter case in the presence of such agents as are capable of liberating iodine
from the alkaline iodides employed.
3.) As new manufactures the iodine compounds of the foregoing second
claiming clause.
Date : 10th 1 f 1900