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Патент USA US2409757

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2,409,756
Patented Oct. 22, 1946
UNITED STATES PATENT ‘OFFICE
i
METHOD FOR OBTAINING 5,5-DIARYL
nrnAN'ronvs
Henry R. Henzc, Austin, Tex., assignor to Parke,
Davis 85 Company, Detroit, Mich., a‘ corpora;
tion of Michigan
No Drawing. Original application September 9, “
1940, Serial No. 356,107. Divided and this ap- ,
plication May, 11,1944, Serial No. 535,212
13 Claims. (Cl. 260--309.5)
1,
t
2
,
tion required for the formation of diarylhydan
toins from diaryl ketones determine .the yield
, This invention relates as a ,method‘for batsm
ing hydantoins from ketones and more particu- >
larly to the preparation of _5,5-diary1hydantoins
which may be obtained. In general, the operat
from diaryl ketones.
ing temperature should be maintained within the
range ‘of 50-15'0° C. and the time required for re
action proportionately varied, from at least 20
hours for the‘lower‘temperatures to at least 1
hour for the higher temperatures, although long
M
>
_‘
I
N
This application is a division of my‘ copending
application, Serial No. 356,107, ?led September. 9',
1940.
’
,
,
An object of this invention is the preparation
of diarylhydantoins from diaryl ketones accord
ing to a new and novel method;
‘
‘ ' I
er times of heating are in general helpful. At
the lower temperatures longer times of heating
I
Other objects of this ‘invention willfjbe'appar
are required to obtain the same gross yield that
ent on perusal of the speci?cation and‘the ap
may be obtained at higher temperatures with
shorter reaction times.‘ For example, while at
_ Hitherto, diarylhydantoins have been ‘prepared
least 20hours ofv heating at 55° is necessary to
from derivatives of benzil and similar compounds. 15 get “a, substantial yield, the same yield can be
obtained‘at 110° by only a few hours of heating
However, no method has been available for the
preparation of 5,5-diarylhydantoins from the core
in a closed vessel 50 as‘ to retain the volatile
components.
responding diaryl ketone's, despite 'the fact-that‘
such ketones are frequently more readily avail;
In general, the diaryl ketone is not completely
able than the corresponding benzil derivatives. 20 converted into the diarylhydantoin. The yield
pended’
claims."
'
‘
‘
’
"
,
‘
'
I have found that 5,5-diarylhydantoins can be
of diarylhydantoin calculated on the basis of the
prepared from‘ diaryl ketones by heating'the lat
amount of diaryl ketone originally introduced into
ter, in the presence of a ‘glycol, such'as‘propylene
the reaction mixture, is ‘termed the gross yield
glycol, with a water soluble‘ cyanide and ammo?
while the yield of diarylhydantoin calculated on
nium carbonate or an equivalent substance 'capa; 25 the basis of the amount of diaryl ketone actually
ble of yielding ammonia and carbon dioxide un-‘
der the conditions of reaction. The‘ reaction
mixture'thus obtained is treated so'as to remove
used up, i. e. the ‘cli?erence between the amount
of diaryl‘ketorie originally introduced and the
' amount recovered, is termed the net yield.
While
any unreacted diaryl ketone and then the hydanev
the gross yield is?conside‘rably diminished by op
toin is isolated, for exampl'eyby acidifying the, 30 erating at ‘lower temperatures and for shorter
alkaline solution.
‘
‘
‘
"
ll
times of heating, the net‘ yield is good under all
'
The reaction‘ may befillustrated. ‘as 'followslfkor,
the case of the'preparation 01,5,5-diphéhjl‘ yj-f
conditions within the range indicated.
'
Excmple.—‘¥Prepdration of 5,5-diphenylhydantoin
""
t i
winy'propyleize‘glycoZ as a solvent
Cali!»
dantoin:
\C=O + (NHOzCOz
"‘
_7
'
+>
I ‘yNaCN'l—-—->“:~»''
e f ,‘
‘To a solution of 91‘ grams of benzophenone in
05H};
“
>
'
‘
500, cc;‘_1ofjjpropylene‘ glycolis added 50 cc.‘ of
V
water,‘45‘ grams of potassium cyanide and.‘ 145
40 gramsfof ammonium carbonate. The mixture is
heated in'a‘ steel jbomb at 110° C. for 6 hours. At
the end of‘this time the‘ mixture is concentrated
under reduced‘pressure to “a paste. This paste is
diluted'with water andiacidi?‘ed with hydrochloric
45
acid. The precipitate is“ collected and leached
with “5%sodiumihydrokide solution. The undis
solve‘d‘ketone is separated and the alkaline solu
tionfacidi?ed with dilute hydrochloric acid. The
60
precipitated 5,5-diphenylhydantoin is collected
and dried. Thusthereris obtained"a‘91% gross
yield of the hydantoin; since about 6 grams of
benzophenone is recovered, the net yield is 97.5 %.
‘ Instead of usin'g’propylene glycol in this‘ ex
; I'v‘havealso iound‘that the conditions-of‘freaci‘j‘.
ample, other glycol solvents maybe employed
55 such as ethylene glycol,- the mono ethyl ether of
21,409,956
3
4
ethylene glycol, the mono methyl ether of ethyl
ene glycol, glycerol and the like.
The effect of variations in this preparation is
shown by the following table:
process, I do not wish my invention to be limited
to a speci?c embodiment but desire rather that it
be construed as broadly as possible in View of the
prior art and the appended claims.
Reactants
>
l ______ __ 9.1 g. benzophenone, 5.0 g. potassium cyanide, 15 g.,
ammonium carbonate.
2
2
_____do
.____do
4
_____do
-
100 cc. propylene glycol _____________ ._ 110“ 0.; 11 hrs"...
100 cc. propylene glycol, 25 cc. water_.
50 cc. propylene glycol, 5 cc. water____
___; do
6 ______ __ 91 g. benzophenone, 45 g. potassium cyanide, 145 g.
ammonium carbonate.
_
'
'
_____ __
Percent
91.4 ____ ._
_
_
110° 0.; 10.5 hrs..110° 0.; 5.5 hrs_-__
95.3 ____ ._
95. 3 ____ ..
110° 0.; 4 hrs .... ._
83. 5
____ ._
60 cc. propylene glycol, 4 cc. water____ .__._do ........... -_
0
60. 3 ____ __
500 cc. propylene glycol, 50 cc. water-_ 110 0.; 6 hrs .... __
91. 2
_
97. 5
a
7 ...... .. 9.1 g. benzoplienone, 4.5 g.‘potassium cyanide, 15 g.
ammonium carbonate.
Conditions
~
_______ __
___
5 ______ ._ 9.1 g. benzophenone, 3.57 g. potassium cyanide, 9.6 g.
ammonium carbonate.
8 ...... ..
Solvent
80 cc. ethylene glycol ________________ .. 110 0.; 10 hrs..-._
r
>
9.1 g. benzophenone, 4.5 g. potassium cyanide, 15.0 g.
'
100 cc. water ........................ .-
ammonium carbonate.
41. 2 .... ._
a
110 0.; 14 hrs_._..
0 .... ._
'
Instead of using benzophenone, I may employ 20
any diaryl ketone containing in the aromatic nu
cleus no groups which are attacked by cyanides
or ammonium carbonate or the combination of
the two. Thus I may practice my invention on
ring-halogenated diaryl ketones, on ring-amino 25
What I claim as my invention is:
1. Process for the preparation of a diaryl hy
dantoin which comprises heating together I at
Such ketones include p
temperatures above 50° C. and for a time, at least
a few hours, permitting accumulation of appre
ciable reaction product, a diaryl ketone, a water
soluble inorganic cyanide, and a reagent derived
from the system NH3—-CO2—Aq capable of re
bromobenzophenone, p-aminobenzophenone, xen
generating all of these latter components under
substituted diaryl ketones, ring-alkylated diaryl
ketones and the like.
yl phenyl ketone, di-p-tolyl ketone, anisyl phenyl
the conditions of the reaction, in the presence of
ketone, etc.
30 a glycol, acidifying the reaction mixture, and sep
arating the diaryl hydantoin thus produced.
Instead of using sodium cyanide or potassium
cyanide in the practice of my invention, I may
employ other water-soluble cyanides such as cal
2. Process for the preparation of a diaryl hy
dantoin which comprises heating together in a
cium cyanide or lithium cyanide. However, I
closed system preventing loss of volatile react
usually preierrtoruse alkali metal cyanides, be 35 ants at temperatures above 50° C. and for a time,
cause of their availability.
Instead of using ammonium carbonate in the
practice of my invention, I may use other equiva
lent sources of carbon dioxide and ammonia.
For example, ammonia gas and carbon dioxide gas 40
at least a few hours, permitting accumulation of
appreciable reaction product, a diaryl ketone, a
water-soluble inorganic cyanide, and a reagent
derived from the system NI-h—-COz—Aq capable
may be pumped into the autoclave containing the
of regenerating all of these latter components
under the conditions of the reaction, in the pres
‘ mixture of the diaryl ketone, the organic solvent
and the water-soluble cyanide, and the mixture .
and separating the diaryl hydantoin thus pro
ence of a glycol, acidifying the reaction mixture,
heated and worked up to obtain the correspond
ing diarylhydantoin. Another. source of ammonia .
and carbon dioxide is ammonium carbamate.
Where in the speci?'cation'and claims the term
ammonium carbonate. is used, it is to be under
stood that it refers to the article of commerce
designated by that name, which however is con_
sidered to be ‘in reality a mixturev of ammonium
bicarbonate and ammonium carbamate.v See fur-v
'50
NI-I3"‘—COz—Aq capable of regenerating all of
these latter components under the conditions of
the reaction, in the presence of a glycol, acidify
ing the reaction mixture, and separating the di
ed., translated by P. C.‘ L. 'I'horne and A. M. Ward,
Nordeman Publishing'Compan'y, New York, 1939) ,
.V
_ ‘
Since the invention may be practiced not only
aryl hydantoin thus produced.
with ammonium carbonate, as above de?ned, but
4. Process for the preparation of a diaryl hy
also with other‘eq'uivalent sources of carbon di
oxide and ammonia in the presence‘ of water, I
have used as a generic expression the phrase “re
a
capable of regenerating’ all of these components
’
f
While the condensation of the diaryl ketone,
the cyanide and ammonium'carbonate' proceeds
in satisfactory yields when the mixture is heated
dantoin which comprises heating together at tem
peratures above 50“ C. and for a time, at least a
few hours, permitting accumulation of appre
agent derived from the system NH§.—.-CO2—Aq
under the conditions of reaction.”
ants at temperatures between 65‘? C. and 150° C.,
and for a time, at least four hours, permitting
accumulation of appreciable reaction product.
a diaryl ketone, a water-soluble inorganic cy
anide, and a reagent derived from the system
ther F. Ephraim, Inorganic Chemistry (third
page 801.
duced.
3. Process for the preparation of a diaryl hy
dantoin which comprises heating together in a
closed system preventing loss of volatile react
05
ciable reaction product, a diaryl ketone, 21. water
soluble inorganic cyanide, and a reagent derived
from the system NI-I_1—COz—Aq capable of re
generating all of these latter components under
the conditions of the reaction, in the presence of
propylene glycol, acidifying the reaction mixture,
and separating the diaryl hydantoin thus pro
duced.
as for example from 65'-150° ‘C., there is a con, 70
5. Process for the preparation of a diaryl hy
dantoin which comprises heating together in a
siderable ,loss‘of‘volatile reactants if an open
vessel is employed. Accordingly, when operating
closed system preventing loss of volatile react
in the ‘range 65-150° C., I prefer to operate in
ants at temperatures between 65° C. and 150° C.,
a closed vessel.
'
'
'
and for a time, at least four hours, permitting
Because of these permissible variations in my 75 accumulation of appreciable reaction product, a
in an open vessel at 50—6_5° C. fora long period of,
time, when higher temperatures are employed
2,409,756
5
diaryl ketone, a water-soluble inorganic cyanide,
and a reagent derived from the system
these latter components under the conditions of
the reaction, in the presence of a glycol, acidify
ing the reaction mixture, and separating the 5,5
diphenyl hydantoin thus produced.
capable of regenerating all of these latter com
ponents under the conditions of the reaction, in
the presence of propylene glycol, acidifying the
10. Process for the preparation of 5,5-diphenyl
hydantoin which comprises heating together at
temperatures above 50° C. and for a time, at least
a few hours, permitting accumulation of appre
dantoin thus produced.
7
ciable reaction product, benzophenone, a water
6. Process for the preparation of a diaryl hy 10 soluble inorganic cyanide, and a reagent derived
dantoin which comprises heating together at tem
from the system NHs——-C‘Oz—-Aq capable of re
peratures above 50° C. and for a time, at least a
generating all of these latter components under
few hours, permitting accumulation of appre
the conditions of the reaction, in the presence of
ciable reaction product, a diaryl ketone, a water
propylene glycol, acidifying the reaction mixture,
soluble inorganic cyanide, and a reagent derived 15 and separating the 5,5-dipheny1 hydantoin thus
from the system NH3—CO2-——Aq capable of re
produced.
generating all of these latter components under
11. Process for the preparation of 5,5-diphenyl
the conditions of the reaction, in the presence of
hydantoin which comprises heating together in a
reaction mixture, and separating the diaryl hy
ethylene glycol, acidifying the reaction mixture,
closed system preventing loss of volatile reactants
and separating the diaryl hydantoin thus pro 20 at temperatures between 65° C‘, and 150° C., and
d-uced.
for a time, at least four hours, permitting accu
'7. Process for the preparation of a diaryl hy
mulation of appreciable reaction product, benzo
dantoin which comprises heating together in a
phenone, a water-soluble inorganic cyanide, and
closed system preventing loss of volatile reactants
a reagent derived from the system NH3-—COz-—Aq
at temperatures between 65° C. and 150° C., and 25 capable of regenerating all of these latter com
for a time, at least four hours, permitting accu
ponents under the conditions of the reaction, in
mulation of appreciable reaction product, a di
the presence of propylene glycol, acidifying the
aryl ketone, a water-soluble inorganic cya~
reaction mixture, and separating the 5,5-diphenyl
hide and a reagent derived from the system
hydantoin thus‘ produced. ,
NH3—CO2—Aq capable of regenerating all of 30
12. Process for the preparation of 5,5-diphenyl
these latter components under the conditions of
hydantoin which comprises heating together at
the reaction, in the presence of ethylene glycol,
temperatures above 50° C. and for a time, at least
acidifying the reaction mixture, and separating
a few hours, permitting accumulation of appre
the diaryl hydantoin thus produced.
ciable reaction product, benzophenone, a water
8. Process for the preparation of 5,5-diphenyl 35 soluble inorganic cyanide, and-a-reagentderived
hydantoin which comprises heating together at
from the system NI-Ia—CO2—Aq capable of re
temperatures above 50° C. and for a time, at
generating all of these latter components under
least a few hours, permitting accumulation of ap
the conditions of the reaction, in the presence of
preciable reaction product, benzophenone, a wa
ethylene glycol, acidifying the reaction mixture,
ter-soluble inorganic cyanide, and a reagent de 40 and separating the 5,5-dipheny1 hydantoin thus
rived from the system NH3-CO2—Aq capable’
produced.
of regenerating all of these latter components
13. Process for the preparation of 5,5-diphenyl
under the conditions of the reaction, in the pres
hydantoin which comprises heating together in
ence of a glycol, acidifying the reaction mixture,
a closed system preventing loss of volatile react
and separating the 5,5-diphenyl hydantoin thus e; an ants at temperatures between 65° C. and 150° C.,
produced.
and for a time, at least four hours, permitting ac
9. Process for the preparation of 5,5-diphenyl
cumulation of appreciable reaction product,
hydantoin which comprises heating together in a
benzophenone, a water-soluble inorganic cya
closed system preventing loss of volatile react
nide, and a reagent derived from the system
ants at temperatures between 65° C‘. and 150° C., 50 NH3—C'O2-—Aq capable of regenerating all of
and for a time, at least four hours, permitting ac
these latter components under the conditions of
cumulation of appreciable reaction product, ben
the reaction, in the presence of ethylene glycol,
zophenone, a water-soluble inorganic cya
acidifying the reaction mixture, and separating
nide, and a reagent derived from the system
the 5,5-diphenyl hydantoin thus produced.
NH3—CO2—-Aq capable of regenerating all of 55
HENRY R. HENZE.
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