Note: Descriptions are shown in the official language in which they were submitted.
4929
~ITLE
Preparation of Acridinones
DESCRIPTION
Technical Field
The present invention relates to 1,2,3,4-
tetrahydro-7-(phenyl)amino-9(lOH)acridinone, its prep-
aration and its use whereby said tetrahydroacridinone
is dehydrogenated in ~he presence of supported palladium
or platinum catalyst to prepare 2-(phenyl)amino-9(lOH)-
acridinone. ~ore specifically, the present invention
relates to 1,2,3,4-tetrahydro-7-(phenyl)amino-9(lOH)-
acridinone and its preparation from either a 2-cyclo-
hexanonecarboxylate ester or ~he reaction product of
cyclohexanone and an oxalate ester with an alkoxide
base, after hydrolysis and decarbonylation to form a
2-cyclohexanonecarboxylate ester by reacting said car-
boxylate ester with N-phenyl-p-phenylenediamine in the
presence of a catalyst to form a phenylaminocyclohex-
enecarboxylate ester and cyclizing to form 1,2,3,4-
tetrahydro-7-(phenyl)amino-9tloH)acridinone.
Background Art
U.S. Patent 3,160,~10 discloses quinacridone-
quinone as one component of a solid solution of two or
more quinacridone derivatives. Such solid solutions
2~ are said to possess enhanced light fastness and tinc-
torial values. However, as compared to compositions
containing quinacridone pigments, compositions con-
taining guinacridonequinone pigments display poor
light fastness. U.S. Patents 3,341,345 and 3,748,162
disclose colorless quinacridonequinone stabilizers
such as N,N'-diphenyl-p-phenylenediamine and 6,13-
dihydro~uinacridone.
Canadian Serial No. 341 100 to Holtje et al filed
1979 December 03 discloses 2-(phenyl)-amino-9tlOH)
CH 1029 35 acridinone, also named 2-anilinoacridone and
1,2,3,4-tetrahydro-7-(phenyl)amino-9(lOH)acridinone,
,~.
1~ 92~3
also named 5,6,7,8-tetxahydro-2-anilinoacridone, as
stabilizers for quinacridonequinone pigment.
Summary of the Invention
Now a process has been found for preparing
stabilizers for quinacridonequinone pigments. One such
stabilizer is 1,2,3,4-tetrahydro-7-(phenyl~amino-9(lOH)-
acridinone which is also called 5,6,7,8-tetrahydro-2-
anilinoacridone.
The 1,2,3,4-tetrahydro-7-(phenyl)amino-9(10H)-
acridinone can be prepared from 2-cyclohexanonecarboxyl-
ate of the formula
o
~ COOR
wherein R is an alkyl group of 1-4 carbon atoms.
The 1,2,3,4-tetrahydro-7-(phenyl)amino-9(lOH)-
acridinone can also be prepared from the aforesaid 2-
cyclohexanonecarboxylate ester that has been prepared
from the reaction of an oxalate ester and cyclohexanone.
Accordingly, a process for preparing 1,2,3,4-
tetrahydro-7-(phenyl)amino-9(lOH)acridinone comprises
(1) reacting a solution of cyclohexanone
and a oxalate ester of the formula
COOR
COOR
where R is an alkyl group of 1-4
carbon atoms at -20 to 60C in
the presence of an alkali metal
alkoxide and a solvent followed
by hydrolysis with aqueous acid
329
to form a 2-cyclohexanoneglyoxylate
ester of the formula
o
~ COCOOR
, J
wherein R is as above;
(2) decarbonylating the glyoxylate
ester at 110-200C in the pres-
ence of an inert high boiling
liquid with the optional addi-
tion of a catalyst to form the
ester of 2-cyclohexanonecarboxyl-
ate of the formula
O
~ COOR
wherein R is as above;
(3) condensing the cyclohexanonecar-
boxylate ester with N-phenyl-
p-phenylenediamine in the pres-
ence of a catalytic amount of a
strong acid at a temperature of
from 80-150C at sufficient pres-
sure to remove byproduct water
to form 2-{4'-[(phenyl)amino]-
phenyl}aminocyclohexenecarboxy-
late ester of the formula
H
~ CO ~ N
5
wherein R is as above;
1~4~32~3
(4) cyclizing the 2-{4'-[(phenyl)-
amino]phenyl}aminocyclohexene-
carboxylate ester by heating at
a temperature of 180-300C in
an inert high boiling liquid to
obtain 1,2,3,4-tetrahydro-7-
(phenyl)amino-9(lOH)acridinone
also named 5,6,7,8-tetrahydro-2-
anilinoacridone of the formula
3~ NH ~
Accordingly, 1,2,3,4-tetrahydro-7-(phenyl)-
amino-9(lOH)acridinone is prepared by a process
comprising
(5) condensing 2-cyclohexanonecar-
boxylate ester of the formula
~ COOR
with N-phenyl-p-phenylenedia-
mine in the presence of a cataly-
tic amount of a strong acid at
a temperature of from 80~150C
at sufficient pressure to remove
byproduct water to form a 2-{4'-
[(phenyl)amino]phenyl}aminocyclo-
hexenecarboxylate ester of the
formula
H
~ CO
1~4'~329
wherein R i5 as above;
(6) cyclizing the 2-{4'-[(phenyl)amino]-
phenyl}aminocyclohexenecarboxylate
ester by heating at a temperature
of 180-300C in an inert high boil-
ing liquid to obtain 1,2,3,4-
tetrahydro-7-(phenyl)amino-9 (lOH) -
acridinone of the formula
o
~ NH~O
The 1,2,3,4-tetrahydro-7-(phenyl)amino-9 (lOH) -
acridinone of this invention can be converted to another
stabilizer for quinacridonequinone pigments, namely
2-(phenyl)amino-9(loH)acridinone al50 called 2-anilino-
acridone of the formula
o
2 0 - 0~NH ~
by a process comprising dehydrogenating 1,2,3,4-tetra-
hydro-7-(phenyl)amino-9(lOH)acridinone by heating in an
inert high boiling liquid in the presence of a catalytic
amount of a supported palladium or platinum catalyst.
The condensation reaction of cyclohexanone
and the oxalate ester is conducted in the presence of
1-1.5 equivalents of an alkali metal alkoxide base
wherein the alkoxide is 1-4 carbon atoms,in an alcohol
or ether solvent at a temperature of -20C to 60~C
followed by hydrolysis with aqueous acid to form 2-
cyclohexanoneglyoxylate ester. Thè preferred amount
of alkali ~etal alkoxide base is 1.1-1.2 equivalents.
~1~4~?29
Representative examples of the alkali metal
alkoxides include sodium methoxide, sodium ethoxide,
sodium propoxide, sodium isopropoxide, sodium butoxide,
potassium methoxide, potassium ethoxide, potassium
propoxide, potassium isopropoxide, potassium butoxide,
etc. The preferred alkali metal alkoxide base is
sodium methoxide because of commercial availability.
The alcohol or ether solvent is an anhydrous
low boiling Cl-C4 alcohol, an ether, or mixtures thereof,
miscible with water. Representative examples of the
solvent include methanol, ethanol, propanol, butanol,
tetrahydrofuran, ethyleneglycol dimethylether and the
like. The preferred solvent is ethanol.
The preferred oxalate esterisdiethyl oxalate.
lS The cyclohexanone condensation reaction with the oxa-
late ester is conducted at a temperature of from
-20C to 60C, inclusive, preferably 22-35~C for a
period of time of 15 minutes to 4 hours in the presence
of the aforesaid solvent and the aforesaid alkali metal
alkoxide. The solvent is optionally removed, e.g., by
vacuum distillation at a temperature of less than 45C
and the resulting mixture hydrolyzed in the presence of
a~ueous acid. If the solvent is not removed prior to
hydrolysis, the solvent is removed after hydrolysis by
extraction. The aqueous layer is then removed and the
remaining organic layer washed several times with a
salt solution to remove inorganic residues. The organic
layer is dried, e.g., by the use of a chemical drying
agent such as anhydrous magnesium sulfate, anhydrous
calcium sulfate, or anhydrous sodium sulfate, or by
vacuum distillation.
Thus, a preferred method of conducting the
cyclohexanone condensation reaction is in an anhydrous
ethanol solvent with l.l-1.2 equivalents of sodium
35 methoxide as the alkoxide at a temperature of 22-35C for
a period of 1/2-2 hours. At this point, an inert high
~492~3
boiling liquid madeupof an eutectic mixtureof 23.5% by
weight biphenyl and 76.5% by weight diphenyl oxide
known as Dowtherm~ A that is required in later steps
is conveniently added. The alcohol is removed by dis-
tillation at 30-40 mm Hg pressure at a temperature be-
low 45C. The remaining mixture is hydrolyzed by the
addition of an aqueous sulfuric acid solution in which
there is incorporated a salt solution. The salt solu-
tion insures that the organic layer will rise to the
top of the mixture. The organic layer after separa-
tion from the aqueous layer is washed several times
with a saturated aqueous sodium chloride solution.
The organic layer is then dried by removing water by
distillation at 20-30 mm Hg pressure at 60-30C. The
2-cyclohexanoneglyoxylate ester produced is a mixture
of the methyl and ethyl esters.
The decarbonylation of the 2-cyclohexanone-
glyoxylate ester is carried out by heating at 120-
200C, preferably 140-150C in the presence of an
inert high boiling liquid and a catalyst. The inert
high boiling liquid is one that will not react with the
ester being heated and that has a boiling point above
the temperature at which the decarbonylation reaction
is run.
Representative examples of said inert high
boiling liquid include Dowtherm~ A, dibutyl phthalate,
alpha and beta methylnaphthalene, o-dichlorobenzene,
p-xylene and the like. The preferred inert high boil-
ing liquid is Dowtherm~ A which is defined above. The
inert high boiling liquid selected is conveniently one
that may be used in subsequent cyclization and dehydro-
genation reactions. Said liquid may be conveniently
added in the step before decarbonylation.
The decarbonylation reaction may be conducted
in the presence of a catalyst, but a catalyst need not be
32~
added. The presence of impurities from the cyclohex-
anone condensation reaction will catalyze the decar-
bonylation reaction. However, it is preferred that a
catalyst be added to insure a satisfactory reaction
since it is possible that said impurities are removed
during washing. Additionally, if the 2-cyclohexanone-
glyoxylate ester has been isolated and purified, e.g.,
by distillation, a catalyst must be added.
The catalyst that may be added is a basic
organic or inorganic compound. Generally, for reasons
of convenience, an inorganic base is preferred. Repre-
sentative examples of the catalyst that may be added
are sodium hydroxide, potassium hydroxide, piperidine,
pyrrolidine, diisopropylamine, calcium hydroxide,
sodium carbonate, potassium carbonate, the sodium salt
of 2-cyclohexanoneglyoxylate ester, the combination of
powdered soft glass and powdered iron and the like.
The preferred bases are sodium hydroxide, potassium
hydroxide and the combination of powdered soft glass
and powdered iron. The sodium or potassium hydroxide
are conveniently added as aqueous solutions, prefer-
ably as 50% by weight aqueous solutions.
The amount of catalyst added is generally
from 0.1-5%, preferably 0.2-1~ by weight based on the
2-cyclohexanoneglyoxylate.
The decarbonylation may also be conducted by
pyrolytic distillation of pure 2-cyclohexanoneglyoxy-
late in the presence of powdered soft glass and pow-
dered iron as is known in the art.
The condensation of the cyclohexanonecar-
boxylate ester with N-phenyl-p-phenylenediamine is
conducted in the presence of a strong acid catalyst at
80-150~C and at a pressure that permits the removal
of byproduct water.
1~4~Z~
Representative examples of the strong acid
used are hydrochloric acid, sulfuric acid, p-toluene-
sul~onic acid, benzenesulfonic acid, trifluoroacetic
acid, naphthalenesulfonic acid, toluenesulfonic acid,
picric acid, o-phosphoric acid, pyrophosphoric acid,
and the like.
If a volatile acid is used, e.g., trifluoro-
acetic acid, an amine such as N-methylaniline may be
added but is not required. The use of such an amine
may tend to help reduce the loss of the volatile acid
catalyst.
Generally, byproduct water is removed by
vacuum distillation.
The condensation of the 2-cyclohexanonecar-
boxylate esters of this invention to form the 2-{4'-
[(phenyl)amino]phenyl}aminocyclohexenecarboxylate ester
can also be carried out by starting with a pure form
of the carboxylate esters that have been prepared and
isolated according to procedures in the prior art.
In such a case, the pure carboxylate ester in a solvent,
e.g., benzene or toluene, is condensed with N-phenyl-p-
phenylenediamine in the presence of a strong acid cata-
lyst and the byproduct water removed by azeotropic dis-
tillation. However, before proceeding to cyclization,
the solvent must be removed, e.g., by vacuum distilla-
tion. Also, the pure isolated carboxylate esters may be
condensed with N-phenyl-p-phenylenediamin~ in an inert
high boiling liquid, e.g., Dowtherm~ A at reduced pres-
sure and with an acid catalyst. Alternatively, the
condensation reaction is carried out with the decar-
bonylation reaction product contained in an inert high
boiling liquid. If the 2-cyclohexanonecarboxylate is a
mixture of esters the resulting 2-{4'-[(phenyl)amino]-
phenyl}aminocyclohexenecarboxylate will also be a mix-
ture of esters.
11~4~3Z~
The cyclizing of the 2-{4'-[(phenyl)amino]-
phenyl}aminocyclohexenecarboxylate is carried out by
heating a solution of the cyclohexene in an inert high
boiling solvent at 180-300C with the removal of
byproduct alcohol. The product formed is 1,2,3,4-
tetrahydro-7-(phenyl)amino-9(lOH)acridinone which is
isolated in high purity by filtration of the reaction
mixture after cooling and washing with an appropriate
solvent, for example, methanol, ethanol, isopropanol,
propyl alcohol, acetone, methyl ethyl ketone, tetra-
hydrofuran, etc.
The product 1,2,3,4-tetrahydro-7-tphenyl)-
amino-9(lOH)acridinone is useful as a stabilizer for
quinacridonequinone pigments.
The inert high boiling liquid for the here-
inbefore described decarbonylation reaction and
cyclization reaction and the dehydrogenation reaction
described hereinafter is any inert liquid whose boiling
point lies above the temperature at which the particular
reaction is run, but not so high as to preclude its
removal from the reaction mixture by distillation at
reasonable temperatures. Representative examples of
the inert high boiling liquid are a-methylnaphthalene,
~-methylnaphthalene, biphenyl, diphenyl oxide, Dowtherm~
A, diethyl phthalate and mineral oils that boil within
the range 180-300C. It is convenient to use the same
inert high boiling liquid used in the decarbonylation
reaction in the cyclization and dehydrogenation
reaction.
The preferred mode of the cyclizing reaction
involves adding the reaction product comprising the
cyclohexene and the preferred inert liquid, Dowtherm~
A, to refluxing Dowtherm~ A at 256-258C in a stirred
vessel. Nitrogen is passed over the mixture to remove
alcohol vapors that are produced. Product precipitates
1~4~3Z~
11
during the reaction and may be isolated by cooling and
filtering followed by washing with methanol.
~ he dehydrogenation reaction is carried out
by heating the tetrahydroacridinone as a suspension or
a solution in an inert high boiling liquid in the
presence of a supported palladium or platinum catalyst.
The dehydrogenation catalyst of this invention is
limited to supported palladium or platinum. The de-
hydrogenation catalyst is critical in achieving a
product that can be prepared in a reasonable reaction
time. Palladium is preferred because it yields the
highest purity product.
The support for the catalyst may be selected
from any known support materials such as carbon,
silicon carbide, silica, alumina, aluminosilicates,
inorganic silicates, inorganic carbonates, pumice,
montmorillonite and the like that are stable under the
reaction conditions. The preferred support materials
are alumina and carbon. Generally, the form of the
support can be powdered, granular or pelletized. Most
preferred are alumina pellets due to commercial avail-
ability and ease in removal from the product slurry.
Carbon powder supported catalysts are especially pre-
ferred because they give higher reaction rates and
yield higher purity products.
The amount of supported catalyst based on the
tetrahydroacridinone can vary widely and depends on the
support chosen. Generally, from 0.1-200% by weight of
supported catalyst based on the tetrahydroacridinone is
used depending on the support. Generally 20-90% by
weight based on the tetrahydroacridinone, preferably 40-
90%, of the supported catalyst is used when the support
is alumina pellets. Generally, 0.1-10% by weight based
on the tetrahydroacridinone, preferably 0.2-5% of the
supported catalyst is used when the support is carbon
powder.
The amount of platinum or palladium on the
support generally varies from 0.1-15% by weight based
on the weight of support depending on the support.
Generally, 0.1-5% by weight of platinum or palladium
based on the weight of alumina pellets, preferably 0.4-
1%, or 2-15% by weight platinum or palladium based on
the weight of carbon powder, preferably 5-10% is used.
In general, the higher the temperature at
which the dehydrogenation is run, the greater the re-
action rate. Generally, he dehydrogenation reaction
is carried out at 180-350~C, preferably 230-300C. The
reaction may be run under pressure to increase the re-
action temperature. Pressures from 1 atm to 20 atm are
generally operable.
Dowtherm~ A is the preferred medium for the
dehydrogenation reaction because of its high boiling
point and because the desired product precipitates when
the medium is cooled. This permits easy isolation of
the product.
The cyclization and dehydrogenation reactions
may be combined for efficiency of operation by adding
the catalyst for dehydrogenation to the refluxing mix-
ture after cyclization without isolation of the tetra-
hydroacridinone formed in cyclization. Alternatively,
the cyclohexene ester can be added to a refluxing, high
boiling inert solvent containing the dehydrogenation
catalyst to carry out the cyclization and the dehydro-
generation in one step.
The product of the process of the invention,
namely, 2-(phenyl)amino-9(lOH)acridinone is also useful
as a stabilizer for quinacridonequinone pigments.
12
The process o~ this invention, among other
things, results in the preparation of 2-(phenyl)amino-
9(lOH)acridinone and 1,2,3,4-tetrahydro-7-(phenyl)-
amino-9(lOH)acridinone of high purity. The process of
this invention achieves this high purity by simply
washing the anilinoacridinones with a solvent such as
methanol, ethanol/ isopropanol and the like. The same
high purity of said anilinoacridinones is obtained
even when the process of the invention is run without
isolating and purifying the intermediates involved.
EXAMPLES
In the following examples provided to further
illustate the invention, all percentages ar~ by weight
unless otherwise indicated.
Example 1
Preparation of 2-(phenyl)amino-9(lOH)acridinone from
cyclohexanone without isolating intermediates
Sodium methoxide (25 g, 0.46 mol) was dis-
solved in 139 ml of anhydrous ethanol in a mechanically
stirred flask equipped with a nitrogen atmosphere. The
solution was allowed to cool to room temperature. A
mixture of 41.7 g (0.43 mol) of cyclohexanone and
67.5 g tO.46 mol) of diethyl oxalate was added slowly
such that the reaction temperature did not exceed 35.
The mixture was stirred at room temperature for 4 hours.
Dowtherm~ A (236 ml) was added. The alcohol was re-
moved by distillation at 30 mm Hg until the reaction
temperature rose to 28C. The thick slurry was acidi-
fied with a mixture of 26.5 g of sodium chloride, 145
ml of water and 45 ml of a 75 volume percent acetic
acid solution. The layers were separated and the
Dowtherm~ A layer was washed twice with 150 ml each of
saturated sodium chloride solution. Water was remo~ed
from the Dowtherm~ A solution by distillation at 75-
85C and 25 mm Hg for 30 minutes.
3Z~ i`
14
A trace of iron powder was added to the re-
action mixture and it was held at 145~ for 2-1/2 hours
to effect decarbonylation.
The mixture was cooled to 50C and 66.5 g
(0.36 mol) of N-phenyl-p-phenylenediamine and 0.8 ml
of trifluoroacetic acid were added. The reaction mix-
ture was heated at 85C and 25 mm Hg for 1 hour, then
125C and 25 mm Hg for 1/2 hour. The solution was
allowed to cool. It was then filtered.
The filtrate was added over 20 minutes to 167
ml of refluxing Dowtherm~ A in a resin kettle equipped
with a nitrogen flow and a steam heated condenser,
a~d containing 40 g of O.5% palladium on 1/~" alumina
pellet catalyst contained in a stainless steel mesh
basket. The addition was done in such a way as to
maintain the reaction temperature over 250C. -The
reaction was held at reflux for 20 hours~ The basket
was raised and the mixture cooled to 80C. The pre-
cipitated solids were filtered and washed well with
methanol. Vacuum oven drying overnight gave 47.~ g
(39.4% yield based on cyclohexanone) of 2-(phenyl)-
amino-9(lOH)acridinone as bright yellow platelets.
Example ~
Preparation cf mixed methyl and ethyl esters of 2-
{4'-l(phenyl)amino]phenyl}aminocyclohexenecarboxylate
from the mixed methyl and ethyl esters of 2-
cyclohexanonecarboxylate
A solution of 18.4 g (0.1 mol) of N-phenyl-
p-phenylenediamine,18.0 g (0.11 mol) of 2-cyclohexanone
carboxylate teffective molecular weight 164 based on
60% ethyl 40% methyl, Aldrich Chemical co~)~o~4 ml of
trifluoroacetic acid and 600 ml of toluene was refluxed
for 3/4 hour in a flask equipped with a ~ean-Stark*
azeotropic water separator. The mixture was cooled
and the solvent removed under vacuum. The resultant
dark oil was dissolved in ether and was treated with
* denotes trademark
14
l~ 3Z~
decolorizing carbon. The mixture was filtered and
the solvent was removed in vacuo. The resultant oil
was dissolved in the minimum amount of methanol. The
solution was seeded and chilled in ice. The resultant
off-white crystals were collected by filtration and
were washed three times with petroleum ether to give
23.2 g (70~ yield) of 2-{4'-[(phenyl)amino]phenyl}amino-
cyclohexenecarboxylate. This process was repeated in
substantially the same way and the material prepared
had mp 74-78 and an infrared spectrum (Nujol mull)
with major bands at 3420 (NH~ and 1650 (ester C=O)
cm
Example 3
Preparation of 1,2,3,4-tetrahydro-7-(phenyl)amino-
9(10H)acridinone from 2-{4'-[(phenyl)amino]phenyl}-
aminocyclohexenecarboxylate ester
One hundred ml of Dowtherm~ A (an eutectic
mixture of biphenyl and diphenyl ether) was heated to
reflux (256C) and purged with nitrogen in a magneti-
cally stirred flask with a steam-heated condenser. A
solution of 10 g of a mixture of the methyl and ethyl
esters of 2-{4'-[(phenyl)amino~phenyl}aminocyclohexene-
carboxylate and 150 ml of Dowtherm~ A was added over 1
hour. A precipitate was formed during the reaction.
The mixture was refluxed for 1 hour after the addition
was complete. The mixture was cooled. Petroleum ether
was added to speed filtration and the precipitated
solid isolated by filtration. The precipitate was
washed thoroughly with petroleum ether and then was
vacuum oven dried at 80 overnight to give 7.8 g (89%
yield) of a cream-colored solid of 1,2,3,4-tetrahydro-
7-(phenyl)amino-9(lOH)acridinone.
This process was repeated in substantially
the same way and the material prep`ared had mp >300C
and an infrared spectrum (Nujol mull) with character-
istic bands at 3390 (NH) and three bands in the region
1580-1620 cm 1.
11~4~Z~
16
Example 4
Preparation of 2-(phenyl)amino-9(lOH)acridinone by
dehydrogenation _ _ _ _
A mixture of 2 g of 1,2,3,4-tetrahydro-7-
(phenyl)amino-9(lOH)acridinone, 100 mg of 10% palladium
on activated charcoal and 100 ml of Dowtherm~ A was
refluxed at 256C with stirring in a nitrogen atmos-
phere. After 1-1/4 hours at reflux, the mixture was
cooled. Product precipitated. Petroleum ether was
added to speed filtration and the product was collected
on a funnel. The product was washed with petroleum
ether. The product was dissolved in N,N-dimethyl-
formamide and filtered to remove the catalyst. The
filtrate was diluted with water to precipitate the
product. The product was filtered and washed with
water. Vacuum drying at 80C overnight gave 1.83 g
(93% yield) of the bright yellow product, 2-(phenyl)-
amino-9(lOH)acridinone.
An infrared spectrum of material prepared in
essentially the same way was superimposable on a
spectrum of material prepared according to the method
described in L. Calb, Ber., Deut. Chem. Gess. 43, 2213
=
(1910) .
Example 5
Preparation of 2-(phenyl)amino-9(lOH)acridinone from
2-{4'-[(phenyl)amino]phenyl}aminocyclohexenecarboxy-
late ester mixture, without isolating intermediates
Dowtherm~ A (100 ml) was brought to reflux
in a mechanically stirred flask with a steam-heated
condenser and nitrogen atmosphere. A solution of 30 g
of a mixture of the methyl and ethyl esters of 2-
{4'-[(phenyl)amino]phenyl}aminocyclohexenecarboxylate
in 300 ml of Dowtherm~ A was added dropwise over 2
hours. Reflux was continued for 1/2 hour after the
addition was complete. The reaction was cooled
slightly and 1.5 g of 10% palladium on carbon was
~4~32'3
added. The mixture was refluxed for an additional 6
hours. The mixture was cooled. The precipitate that
formed was filtered. The precipitate was washed with
petroleum ether. The precipitate was dissolved in 150
ml of warm dimethylformamide (DMF). The DMF solution
was filtered and the solid remaining on the funnel was
washed with an additional 75 ml of DMF. The combined
DMF filtrates were diluted to 2 liters with water. The
product precipitated and was collected on a funnel and
was washed well with water. Vacuum oven drying at 80C
for 2 days gave 25 g t96% yield) of 2-(phenyl)amino-
9(lOH)acridinone.
Example 6
Decarbonylation of 2-cyclohexanoneglyoxylate ester
mixture in solution
Ten grams of a mixture of the methyl and
ethyl esters of 2-cyclohexanoneglyoxylate prepared as
described in H. R. Snyder, ~. A. Brooks and S. H.
Shapiro, Organic Synthesis Collective Vol. II, 531,
0.1 g of powdered soft glass, a trace of iron powder
and 75 ml of Dowtherm~ A were heated to 200C in a
nitrogen atmosphere, with stirring. Gas evolution
stopped after 2 hours at 200C. Thin layer chromato-
graphic analysis (silica gel plates, eluted with 10
parts hexane:l part acetone then stained with a solu-
tion of ferric chloride in ethanol) showed complete
conversion to 2-cyclohexanonecarboxylate ester mixtures
(wherein R was methyl and ethyl).
Example 7
Preparation of 2-(phenyl)amino-9(lOH)acridinone from
2-cyclohexanonecarboxylate ester without isolating
intermediates
A solution of 18.6 g (0.1 mol) of practical
grade N-phenyl-p-phenylenediamine, 18.0 g (0.11 mol)
of a mixture of the methyl and ethyl esters of 2-
cyclohexanonecarboxylate (Aldrich Chemical Co., 40%
45~2~3
18
methyl, 60% ethyl), 0.2 ml of trifluoroacetic acid and
600 ml of toluene was refluxed in a flask equipped
with a Dean-Stark azeotropic water separator for 1
hour. The solvent was removed under vacuum. The re-
sultant dark oil was dissolved in 200 ml of warm
Dowtherm~ A and was added dropwise over 1 hour to 90
ml of refluxing Dowtherm~ A which was contained in a
flask equipped with a steam-heated condenser, nitrogen
flow and a mechanical stirrer. Heating was continued
for 1 hour after the addition was complete. 1.45 g of
10% palladium on carbon was added and the mixture was
refluxed for an additional 13 hours. The mixture was
cooled and the solids that precipitated were collected
on a funnel. The solids were washed with four 75 ml
aliquots of methanol. The solids were dissolved in
warm DMF and filtered to remove catalyst. The DMF
filtrate was diluted with water to precipitate product.
The product was collected on a funnel and washed well
with water. Drying in a vacuum oven at 120C overnight
gave 24.54 g (86% yield) of product 2-(phenyl)amino-
9(10H)acridinone.
Example 8 - Best Mode Starting with Carboxylate Esters
Preparation of 1,2,3,4-tetrahydro-7-tphenyl)amino-
9(lOH)acridinone from 2-cyclohexanonecarboxylate
ester in Dowtherm~ A
A mixture of 18.4 g (0.1 mol) of N-phenyl-
p-phenylenediamine, 18.0 g (0.11 mol) of a mixture of
the methyl and ethyl esters of 2-cyclohexanonecarboxy-
late (Aldrich Chemical Co., 40% methyl, 60~ ethyl
ester), 0.2 ml of trifluoroacetic acid and 100 ml of
Dowtherm~ A was heated and stirred at 85-90 and 25 mm
Hg for 1 hour, then at 115-120 and 25 mm Hg for 1/2
hour. The resultant solution was cooled to room tem-
perature and was transferred to a dropping funnel
using 25 ml of Dowtherm~ A to wash the glassware. This
18
~4~32~
19
solution was added dropwise over 1 hour to 25 ml of re-
fluxing Dowtherm~ A in a mechanically stirred flask
equipped with a steam heated condenser. Heating was
continued for 1 hour after the addition was complete.
The mixture was cooled to room temperature and the
precipitated product was collected by filtration. The
product was washed well with four 50 ml aliquots of
methanol. Vacuum oven drying at 80C overnight gave
22.6 g (78% yield) of the product 1,2,3,4-tetrahydro-
7-(phenyl)amino-9(lOH)acridinone.
Example 9
Preparation of 1,2,3,4-tetrahydro-7-(phenyl)amino-
9(lOH)acridinone from 2-cy~ohexanonecarboxylate ester
A mixture of 73.6 g (0.4 mol) of N-phenyl-
p-phenylenediamine, 72 g (0.4 mol) of a mixture of the
methyl and ethyl esters of 2-cyclohexanonecarboxylate
(~ldrich Chemical Co., 40~ methyl, 60~ ethyl ester)
0.8 ml of trifluoroacetic acid and 1200 ml of toluene
was refluxed for 1 hour in a flask equipped with a
Dean-Stark water separator. The solvent was removed
under vacuum and the resultant oil was dissolved in
500 ml of Dowtherm3 A. This solution was added over
1 hour to 100 ml of refluxing Dowtherm~ A in a flask
equipped with mechanical stirrer, nitrogen flow and a
steam heated condenser. Reflux was continued for 1
hour after the addition was complete. The mixture was
cooled to room temperature and the precipitated product
was filtered. The product was washed with four 200 ml
aliquots of methanol. Vacuum oven drying at 80C over-
30 night gave 9g.9 g (89% yield) of 1,2,3,4-tetrahydro-
7-(phenyl)amino-9(lOH)acridinone. The product was
identified by microanalysis.
Anal. calc'd for ClgH18N20: C, 78.59; H, 6-24; N, 9-65-
Found: C, 78.37; H, 6.11; N, 9.77
78.41 6.42 9.85
19
~4~329
Example 10
Preparation of 2-(phenyl)amino-9(lOH)acridinone from
1,2,3,4~tetrahydro-7-(phenyl)amino-9(lOH)acridinone
A mixture of 70 g of 1,2,3,4-tetrahydro-7-
(phenyl)amino-9(lOH)acridinone and 700 ml of Dowtherm~
A was brought to reflux in a 2 liter resin kettle, in a
nitrogen atmosphere. A stainless steel mesh basket con-
taining 14.5 g of O.5% palladium on 1/8 inch alumina
pellets was lowered into the reaction mixture. The mix-
ture was refluxed for 18 hours. The basket was removedfrom the reaction mixture, which was then allowed to
cool. The precipitated product was collected on a fil-
ter and was washed with four 350 ml aliquots of methan-
ol. Vacuum oven drying at 100C overnight gave 61.4 g
(89%) of the product that was analyzed by microanalysis.
Anal. calc'd for ClgH14N20: C, 79.69; H, 4.93; N, 9.78-
Found: C, 78.85; H, 4.91; N, 9.61
78.76 5.14 9.60
Example 11 - Best Mode for the Preparation of 1,2,3,4-
tetrahydro-7-(phenyl)amino-9(lOH)acridinone from cyclo-
hexanone, without isolating intermediates
A mixture of 139 ml of absolute ethanol, 25 g
of sodium methoxide and 67.5 g of diethyloxalate was
prepared in a mechanically stirred 1 liter flask under
nitrogen atmosphere. The mixture was cooled to 22C.
Cyclohexanone (41.7 g) was added dropwise, keeping the
temperature below 35. The mixture was stirred for lJ2
hour at room temperature, then 236 ml of Dowtherm~ A
were added. The alcohol was removed by distillation at
35 mm Hg until the reaction mixture temperature reached
29. The mixture was hydrolyzed by adding a solution
of 24 g of concentrated sulfuric acid, 216 ml of water
and 9 g of sodium chloride. An additional 3 g of
sodium chloride were added to speed separation of the
layers. The layers were separated and the organic layer
was washed three times with saturated aqueous sodium
chloride. The organic layer was then dehydrated by
distillation at 25 mm Hg and 65 for 3/4 hour. A 50%
~4~3Z~ `
aqueous solution of sodium hydroxide (0.6 g) was added
and the mixture heated at 145 for 2.5 hours to effect
decarbonylation. An infrared spectrophotometric analy-
sis of the reaction mixture showed 0.311 mole of 2-
cyclohexanonecarboxylate ester. One equivalent
(57.20 g) of N-phenyl-p-phenylenediamine and 0.8 ml
of trifluoroacetic acid were added. The solution was
heated at 85 and 25 mm Hg pressure for 1 hour, then
125 and 25 mm Hg for 1/2 hour to bring about conden-
sation. This solution was then added dropwise to 176 mlof refluxing Dowtherm~ A in a mechanically stirred
flask with a nitrogen sweep through the flask and a
steam heated condenser. The addition was adjusted such
that the reaction temperature did not drop below 250C.
Reflux was continued for 1 hour after the addition was
complete. The mixture was cooled to 90-100 and fil-
tered ~o isolate the product. The filter cake was
washed well with methanol and was dried in a vacuum
oven to give 66.75 g (54%, corrected for loss of product
due to above IR sample) of 1,2,3,4-tetrahydro-7(phenyl)-
amino-9(lOH)acridinone.
Example 12
Preparation of 1,2,3,4-tetrahydro-7-(phenyl)amino-
9(lOH)acridinone from cyclohexanone, without isolating
intermediates. No decarbonylation catalysts used.
Sodium methoxide (25 g, 0.46 mol) and 67.5 g
of diethyloxalate (0.46 mol) were dissolved in 139 ml
of anhydrous alcohol in a mechanically stirred flask
equipped with a nitrogen atmosphere. ~he solution was
allowed to cool to 22. Cyclohexanone (41.7 g, 0.43
mol) was added at a rate such that the reaction temper-
ature did not exceed 35. The mixture was then stirred
overnight at room temperature. Dowtherm~ A (236 ml)
was added and the mixture was distilled at 25 mm Hg
until the reaction temperature reached 29. The re-
sultant slurry was hydrolyzed by adding a mixture of
Z~
22
26.5 g of sodium chloride and 45 ml of 75 volume per-
cent aqueous acetic acid in 145 ml of water. An addi-
tional 84 ml of water was added to speed the separa-
tion. The layers were separated and the Dowtherm~ A
S layer was washed twice~ each time with half of a solu-
tion of 90 g of sodium chloride in 250 ml of water
(a saturated solution). The aqueous layers were
discarded.
Water was removed from the Dowtherm~ A layer
by vacuum distillation at 65 and 25 mm Hg for 1/2
hour.
Vacuum was removed and the solution was
heated to 145 for 2.5 hours to bring about decarbon-
ylation. No additional catalysts were used.
N-phenyl-p-phenylenediamine (66.5 g, 0.36
mol) and 0.8 ml of trifluoroacetic acid were added.
The reaction mixture was heated at 85C and 25 mm Hg
for 1 hour, then at 125C and 25 mm Hg for 1/2 hour.
The mixture was filtered, using 30 ml of fresh
Dowtherm~ A to wash the glassware. The solution was
placed in a dropping funnel and added dropwise to 75
ml of vigorously refluxing (256) Dowtherm~ A in a
mechanically stirred flask equipped with a nitrogen
purge and a steam heated condenser. The material was
added over 1-1/2 hours. Ref~uxing was continued for
1 hour after the addition was complete. The mixture
was cooled and the precipitated product was isolated
by filtration. The product was washed well with
methanol and vacuum oven dried to give 61.2 g (50%
yield) of the acridinone compound indicated above.
This yield is corrected for in-process samples taken.
Example 13 - Best Mode Starting With Cyclohexanone
Preparation of 2-(phenyl)amino-9(~OH)acridinone
using caustic as the decarbonylation catalyst
A solution of sodium methoxide (25 g, 0.46
~1~4~3Z3
23
mol)~diethyloxalate (67.5 g, 0.46 mol) and 139 ml of
anhydrous ethanol was prepared in a mechanically
stirred flask under a nitrogen atmosphere. The solu-
tion was cooled to 22. Cyclohexanone (41.7 g, 0.43
mol) was added at a rate such that the reaction tem-
perature did not exceed 35. The mixture was stirred
for 1/2 hour, then 236 ml of Dow~herm~ ~ was added.
Alcohol was distilled out at 35 mm until the reaction
temperature reached 29. The mixture was hydrolyzed
by addition of a solution of 17.1 g of sodium chloride,
41 ml of a 75% (v/v) solution of acetic acid and 192 ml
of water. The layers were separated and the Dowtherm~
A layer was washed three times with 125 ml portions of
saturated sodium chloride. An emulsion in the last
salt wash was broken by filtration. The reaction mix-
ture was dewatered by distillation at 65 and 25 mm Hg
for 3/4 hour. Sodium hydroxide (0.6 g of a 50~ aqueous
solution) was added and the mixture heated at 145 for
2.5 hours. An infrared analysis showed 0.336 mol of 2-
cyclohexanonecarboxylate ester present. One equivalent(61.8 g) of N-phenyl-p-phenylenediamine and 0.8 ml of
trifluoroacetic acid were added. The mixture was
heated at 85 and 25 mm Hg for 1 hour, then 125 and
25 mm Hg for 1/2 hour. This amine solution was added
slowly to 176 ml of refluxing Dowtherm~ A, containing
2 g of 10% palladium on charcoal catalyst. The
Dowtherm~ A/palladium suspension was contained in a
mechanically stirred flask with a nitrogen atmosphere
and a steam heated condenser. The rate of addition
of the amine solution was such that the pot tempera-
ture remained over 250. Reflux was continued for
8 hours. The mixture was cooled. The resulting pre-
cipitate was washed well with meth~anol. The precipi-
tate was dissolved in 300 ml of warm dimethylformamide.
This solution was filtered to remove the catalyst.
1~44~9
24
The filtrate was poured into 3liters of water. The
precipitated product was filtered and was washed with
water and was vacuum oven dried to give 52.7 g, 43%
yield of the acridinone indicatecl above, corrected for
samples removed.
Example 14 - Best Mode for dehydrogenation of 1,2,3,4-
tetrahydro-7-(phenyl)amino-9(lOH)acridinone
The following ingredients
8.2 g of 10% Pd on carbon
164.3 g of 1,2,3,4-tetrahydro-7~(phenyl)-
amino-9(lOH)acridinone
1400 ml of Dowtherm~ A (as defined
hereinbefore)
were placed in a 3.5 1 reactor, equipped with an exter-
nal heater and a condenser, agitator, nitrogen purgemeans and a discharge line with an internal filter of
0.5 micron pore size leading to a receiver. The reactor
was heated and the contents refluxed for 2-1/2 hours
under a nitrogen purge at about 250C and 1 atmosphere
of pressure. The contents of the reactor were fil-
tered via the discharge line by pressurizing the reactor
to 29 psig to push the contents through the filter in
the discharge line into the receiver leaving the cata-
lyst and a small heel in the reactor. The yield of
2-(phenyl)amino-9(lOH)acridinone was 82.5% by weight.
The above was repeated using the same amounts
of the same ingredients except that 1.2 g of the cata-
lyst were added to the heel of the above run. Four
runs gave yields of 89.5%, 94.4%, 93.7% and 95.2%.
Comparative Examples A-I
The process of Example 4 was repeated except
that the catalyst, support and starting material shown
in the table below were used. Analysis of the reaction
mixture by thin layer chromatography indicated that in
all cases there was considerable starting material in
1~4~329 ``
the reaction mixture and only a small amount of 2-
~phenyl)amino-9(lOH)acridinone. Therefore, none of the
base metal catalysts shown were considered useful to
dehydrogenate 1,2,3,4-tetrahydro-7-(phenyl)amino-
9(lOH)acridinone.
DEHYDROGENATION
Comparative Catalyst
Examples_ Metal Support Amount
A _ A12O3 fumed 2.5 g
B _ A12O3 pellets 5 g
C MnO2 - 0.25 g
D NiO (15%)A12O3 pellets 1 g
~7.5~ Cr)A12O3 pellets 1 g
F F(e~)3A12O3 pellets 1 9
G Ni (60~ Ni)kieselguhr 0.5 9
H MoO3 A12O3 pellets 5 g
(10-20~ Mo)
I - Davison 4A 0.23 g
Molecular sieves
_____________________________________________________________
1,2,3,4-Tetrahydro- 2-(Phenyl)-
7-(phenyl)amino- amino-9(lOH)-
Comparative9(10H)acridinone Dowtherm~ A acridinone
25Examples A unt Amount Amount
A 2.5 g 25 ml Trace
B 5 g 50 ml Trace
C 2.5 g 25 ml Trace
D 2 g 50 ml Trace
E 2 g 50 ml Trace
F 2 g 50 ml Trace
G 2 g 50 ml Trace
H 5 g 50 ml Trace
I 1 g 50 ml Trace
Z9
26
INDUSTRIAL APPLICABILITY
. The process of the invention permits the
preparation of intermediates for the preparation of
stabilizers for quinacridonequinone pigments. The
stabilizers prepared include the compounds 2-(phenyl)-
amino-9(lOH)acridinone and 1,2,3,4-tetrahydro-7-
(phenyl)amino-9(lOH)acridinone.
The application is a division of copending application
Serial No. 359 009 filed 1980-08-26.
26
