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Патент USA US2116104

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‘Patented May 3, 1938
'
2,116,104
UNITED STATES
‘
PATENT oFFicE,
2,116,104
3.5 - DIIODO ‘- 4 - HYDROXY
ACYLOPHENONE
COMPOUND-S AND M'ET'HOD
‘
FOR
PRO-
7
: DUCING THE‘ SAME
Max D‘ohrn, Berlin-Charlottenburg, and Paul
Diedrich, Finkenkrug,
(Osthavellan?) ,
Ger
many, assignors to Schering A. G., Berlin, Ger
many, a corporation‘ of Germany
No Drawing. Application July 10, 1936, Serial
No. 90,004; ‘In Germany March 13, 1935
23 Claims. (01‘; 260-131)
‘ This invention relates to 3.5-diiodo-4-hydroxy
tives substituted in the hydroxy group, and a
13.6 grams of 4-hydroxy-acetophenone are dis
solved in 140 ccs. cr2o% hydrochloric acid and‘
1.4 litres of water‘ and treated with stirring at
method for producing the same.
‘
‘ Iodine derivatives of hydroxy-acetophenones
room temperature with a solution of 33 grams of
iodine monochloride in 50 cos. of 20% hydro
acetophenone, its homologues and their deriva
‘substituted in the 3 and 5 positions‘have not ,chloric'acld drop by drop. The diiodo compound
hitherto been described. Experiments havefshown‘ immediately separates in a crystalline form and
that by iodination of o- and m-hydroxy-aceto
on recrystallization from alcohol for puri?cation,
phenone only mono-iodo acetophenones are pro
is obtained in colourless needles of M. P. 1'72-1'73°
10 duced. - In accordance with the‘present invention, C. The yield amounts to 36.7 grams-95% of the 10
however,‘ from‘ the p-hydroxy-acetophenone by. ;theory. The 3.5-diiodo-4-hydroxy—acetophenone
iodination 3.5-diiodo-4-hydroxy-acetophenone is is‘easily soluble in ether and chloroform, more
obtained in good yield. The io-dination is car
ried out, for‘ example, in such a manner that 2
dili‘icultly soluble in benzene and alcohol; it is
insoluble in water.
‘ l6 mols of iodine monochloride are allowed to react
Example 2
at ordinary temperature upon p-hydroxy-aceto
phenone dissolved in dilute hydrochloric acid; ‘
The 3.5-diiodo-fl-hydroxy-acetophenone then sep
3.5 - diiodo - 4 - me'thoxy-acetophenone,
whose
structural formula is
arates‘in a. short time in ‘a practically quantita
20
tive yield.
20
Another object‘ of this invention consists in
subjecting- instead of the above mentioned p
hydroxy-acetophenone, its homologues to the ‘ac
tion of iodinating agents.
2‘
‘»
‘ ‘
'
42.6 grams of the potassium salt of 3.5-diiodo
According to a further feature of the invention
4=~hydroxy-acetophenone are heated in 150 cos.
the hydrogen of the hydroxyl group in these
compounds can be substituted by other residues
such as alkyl, alkoxy, alkyl~carboxy, alkyl-sul
iodide for 6 ‘hours to boiling. From the hot ?l
tered solution the methoxy derivative separates
ionic, arylfheterocyclic and other residues; in
general, the hydroxy is replaced by a group which
30 on
‘hydrolysis is replaced by a hydroxy group.
The introduction of the substituents into the
hydroxyl group takes place advantageously by
interaction of suitable salts of 3.5-diiod'o-4
35 hydroxy-acetophenone or its homologues in alco
holic or benzene ‘suspension with the correspond
of absolute alcohol with 14.5 grams of methyl
out in colourless needles. These are ?ltered with
suction, washed with dilute sodium carbonate so
lution and water and recrystallized from alcohol,
forming needles of M. P.'97—98° C.
Example 3
3.5-diiodo-4-ethoxy-acetophenone, having the
structural formula
ing‘ halogenides or also by direct interaction of
I
the components without application of solvents.
The products of the present invention, the 3.5
l
CHaC 000021;.‘
‘ 4d diiodo-4-hydroxy-acetophenone, its‘ homologues
and their substitution products ‘are intended to
?nd application as intermediate products in the
manufacture of disinfecting agents, pharmaceu
tical products, X-ray contrast media and the like.
The following examples illustrate the‘ invention
without, however; limiting the same to them.
Example 1
I
3.5-diiodo-4-hydroxyl-acetophenone; the struc
50 tural formula‘being
‘
‘
I
'30
,7
540
i .
,
I
35
a
42.6 grams of the potassium salt of 3.5-diiodo
4-hydroXy-acetophenone are heated in 150 cos.
of absolute alcohol with 16 grams of ethyl iodide
and the solution worked up as. described in Ex
ample 2, giving needles of M. P. 93-94° C.
Example 4
3.5-diiodo - 4 - hydroxy-methyl-ether-acetophe
'50
none, whose formula is
I
I
2
2,116,104
42.6 grams of the potassium salt of 3.5—diiodo
4-hydroxy-acetophenone are treated in the hot
in 150 cos. of benzene with 8.1 grams of chloro
methyl-ether. It is thereupon ?ltered hot and
the benzene distilled-off. The residue after treat
ment with dilute sodium carbonate solution is
recrystallized from alcohol forming needles of
M. P. 96-97” C.
Example 5
10
3.5 - diiodo — 4 - hydroxy-ethoxy-acetophenone,
having the structural formula
chloride in 50 cos. of 20% hydrochloric acid at
room temperature. The diiodo compound pre~
cipitates immediately and is further puri?ed by
recrystallization from dilute alcohol. The col
ourless needles of 3.5-diiodo—4—hydroxy-1-(y
hydroxy-butyro-)phenone contain 1 mol. of wa
ter of crystallization and have a M. P. of 106° C.
(the v-bromo-butyro-phenol used as starting
material for the production of ll-hydroxy-l-(v
hydroXy—butyro-)phenone, is produced from 10
phenol-v-bromo-butyryl-chloride and has a boil
ing point of 173-175" C. at a pressure of 15 mm).
In the same manner as described above the
I
l
‘4-hydroxy-l-propiophenone and the 4—hydroxy~
l-butyro-phenone, both obtained by rearrang 15
ing the corresponding propio- or butyro-phe
nols, for instance, with metal halogenides such as
15
I
42.6 grams of the potassium salt of diiodo
hydroxy-acetophenone are heated on the water
20 bath with 30 grams of ethylene chlorhydrin until
the potassium salt has disappeared. The mass
is poured into water, rendered alkaline with so
aluminum chloride, or other homologue of the
aceto-phenone may be converted into the cor
20
responding diiodo compounds.
The above reactions may be represented as
follows:
l
25
H
on
I——
+12 0
AlOls-l-HaO +1101
l
COOHaCHzCHrOH
30
—I
l
COCHzCHzCHaOH
30
p-Brom-butyrophenol———)4-hydroxy-l- ('y-hydroxy- -->3,6-diiod-4—hydroxy-1- (v
butyro-) phenon
hydroxybutyro) phonon
dium carbonate and extracted with chloroform.
The chloroform residue after some time becomes
crystalline and has the M. P. 94~95° C.
Example 6
3.5-diiodo-1—aceto~4-phenoxy-acetic acid of the
formula
I
I
CH3OO-—QOCH3COOH
I
45
r
42.6 grams of the potassium salt of diiodo
hydroxy-acetophenone are boiled under reflux
with 50 cos. of chloracetic acid ethyl ester until
the reaction is complete. The hot ?ltered solu
50 tion leaves on concentration under reduced pres
sure a light brown oil which soon solidi?es to
crystals. Recrystallization from dilute alcohol
yields the 3.5-diiodo-1-aceto—4~phenoxy acetic
acid ethyl ester in needles of M. P. 104.50 C. The
hydrolysis of the ester takes place by boiling for
1 hour with 20 times the quantity of hydrochlo
ric acid (D-—1.19). The free 3.5-diiodo-1-aceto
‘i-phenoxy-acetic acid forms on recrystallization
from alcohol light yellow prisms of M. P. 1785’ C.
60
Example 7
3.5 — diiodo-4—hydroxy-1-('y-hydroxy - butyro~)
phenone, having the structural formula
.
65
I
I
l
HOOHzCHzCHaCO—®-OH
l
I
13.0 grams of 4-hydroxy-1-('y-hydroxy-buty
70 ro-)phenone of the M. P. 144° 'C., as it is ob
Of course, many changes and variations in
the reaction conditions, the agents used, the sol
vents, the reaction temperature, the puri?cation
methods and the like may be employed by those
skilled in the art in accordance with the prin
ciples set forth herein and in the claims an
nexed hereto.
‘What we claim, is:
1. A method for the production of 3.5-diiodo
4-hydroxy acylophenone compounds, comprising
subjecting 4-hydroxy-acylophenone compounds
to the action of an iodinating agent capable of
introducing two iodine atoms into the molecule
of such compounds.
2. A method according to claim 1, wherein
iodine chloride is used as iodinating agent.
3. A method for the production of 3.5-diiodo
4-hydroxy acetophenone compounds, comprising
subjecting 4=~hydroxy acetophenone to the ac
tion of an iodinating agent capable of introduc
ing two iodine atoms into the molecule.
4. A method for the production of 3.5-diiodo~
4-hydroxy acetophenone compounds, comprising
subjecting é-hydroxy acetophenone to the ac
tion of an iodinating agent capable of introduc
ing two iodine atoms into the molecule and replac
ing the hydroxy group with a group which on
hydrolysis can be reconverted into the hydroxy
group.
7
5. A method for the production of 3.5-diiodo
4-hydroXy acetophenone compounds, comprising
subjecting 4-hydroxy acetophenone to the ac 65
tion of an iodinating agent capable of introduc
ing two iodine atoms into the molecule and re
acting the 3.5-diiodo-4-hydroxy acetophenone so
obtained with an etherifying agent.
6. A method for the production of 3.5-diiodo 70
tained by rearranging v-bromo-butyro-phenol by
4-hydroxy acetophenone compounds, comprising
means of aluminum chloride are dissolved in 150
subjecting 4-hydroxy acetophenone to the ac
tion of an iodinating agent capable of introduc
cos. of 20% hydrochloric acid and 1.5 liters of
water. To this solution there is added while
75 stirring a solution of 33 grams of iodine mono
40
ing two iodine atoms into the molecule and re
acting the 3.5—diiodo-4-hydroxy acetophenone so 75
2,116,104
obtained with a compound selected from the
group consisting of halogenated carboxylic and
sulfonic acids and their esters.
7. A method for‘ the production of 3.5-dii0do
none of the general formula
ll-hydroxy acylophenone compounds, comprising
subjecting 4-hydroxy acylophenone compounds
and the structural formula
to the action of an iodinating agent capable of
introducing two iodine atoms into the molecule
of such compounds, and reacting the 3.5-diiodo
10 4-hydroxy acylophenone compound so obtained
with an etherifying agent.
8. A method for the production of 3.5-diiodo
4-hydroXy acylophenone compounds, comprising
subjecting li-hydroxy acylophenone compounds
15 to the action of an iodinating agent capable of
introducing two iodine atoms into the molecule
of such compounds, and reacting the 3.5-diiodo
ll-hydroxy acylophenone compounds so obtained
with a compound selected from the group con
20 sisting of halogenated carboxylic and sulfonic
acids and their esters.
9. A method for the production of 3.5-diiodo
4i-hydroxy acylophenone compounds, comprising
effecting rearrangement of whalogeno acylophe
25 nol compounds in the presence of metal halo
genides, and subjecting the Ll-loydroxy acylo
phenone compounds obtained thereby to the ac
tion of an iodinating agent capable of introduc
ing two iodine atoms into the molecule of such
30 compounds.
10. A method for the production of 3.5—diiod0—
é-hydroxy acylophenone compounds, comprising
effecting rearrangement of y-halogeno acylophe
35
,3
14. A 3.5-diiodo-4-hydroxy ethoxy acetophe
I
0113.0 o-Qopmomon
I
I
having a melting point of 94~95° C.
15. A 3.5-diiodo-4-hydroxy-l-('y-hydroxy bu~
tyro-)phenone of the general formula
HO‘.CH2.CH2.CH2.CO.C6H2I2.O
and the structural formula
I
l
noor-nomcmoo-O-on
I
20
I
having a melting point of about 106° C.
16. The method according to claim 3 wherein
the iodinating agent is iodine chloride.
17. The method of producing 3.5-diiodo-4
alkoxy acylophenone compounds which comprises
reacting upon a metal compound of a 3.5-diiodo-4
hydroXy acylophenone with an alkyl ester capable
of removing the metal.
18. A 3.5-diiodo-‘l-hydroxy acylophenone com
pound of the general formula RCOCcHzIzDR’
corresponding to the structural formula
nol compounds in the presence of metal halo
genides, and subjecting the 4-hydroxy acylo
phenone compounds obtained thereby to the ac
tion of an icdinating agent capable, of introduc
ing two iodine atoms into. the molecule of such
40 compounds and replacing the hydroxy group with
a group which on. hydrolysis can be reoonverted
into the hydroxy group.
11. A 3.5-diiodo-4-hydroxy acylophenone com
pound of the general formula R.CO‘.C6H2I2.0R’
45 wherein R indicates a hydrocarbon radical and
OR’ an etheri?ed hydroxyl group.
12. A 3.5-diiodon4-hydroxy acetophenone com~
pound of the general formula CH3.CO.CcI-I2I2.0R'
wherein OR’ indicates an etheri?ed hydroxyl
50 group.
13. A 3.5-diiodo~l1-hydroxy acetophenone com
‘ pound of the general formula CH3-CO.C6H2.I2.0H
and the structural formula
wherein R is an aliphatic radical capable of
forming part of an acyl group and R’ is an or 40
ganic substituent group capable of being replaced
by hydrogen with the aid of hydrolysis.
19. A 3.5-diiodo-4-hydroxy acylophenone com
pound of the general formula RCeHzIzOR’ where
in R is an acyl radical and OR’ is‘a member of
the group consisting of hydroxyl and groups
which by hydrolysis can be replaced by hydroxyl.
20. A 3.5-diiodo-4-hydroxy acylophenone com
pound as de?ned in claim 11, wherein R’ is a
hydrocarbon ' radical.
21. A 3.5-diiodo-li?hydroxy acetophenone compound as de?ned in claim 11, wherein R’ is an
acid group.
22. A 3.5-diiodo-‘l-hydroxy acylophenone com»
55
pound as de?ned in claim 12, wherein R’ is a
hydrocarbon radical.
23. A 3.5-diiodo-4-hydroxy acetophenone com
pound as de?ned in claim 12, wherein R’ is an
acid group.
60
having a melting point of 172-1'73° C.
'
MAX DOHRN.
PAUL DIEDRICH.
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