Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
~08~937
The present invention relates to a process for the
manufacture of iso-imides or mixtures of iso-imides and imides.
Various processes for the manufacture of N-substituted
isomaleimides and isophthalimides and of N,N'-bis-isomaleimides
and N,N'-bis-isophthalimides are known from the literature.
Thus, N-substituted maleamic or phthalamic acids and also N,N-
bis-maleamic acids or N,N'-bis-phthalamic acids can be converted
into the corresponding iso-imides in the presence of various
dehydrating agents, such as acetic anhydride, trifluoroacetic
anhydride, acetyl chloride, thionyl chloride or dichloroacetyl
chloride, preferably with the additional use of a tertiary
amine, such as triethylamine, or in the presence of carbodi-
imides, for example, dicyclohexylcarbodiimide ~compare U.S.
Patent Specifications 2, 995 5 577, 2,998,429, 3,035,065 and
7,472,817 and also J. Org. ~hem., 28, 2, 018-2,024 (1963), 34,
2,275-2,279 (1969) and 36, 821-823 (1971)]. According to
U.S. Patent Specification 2,980,701, ammonium salts of N-
substituted maleamic acids can also be converted into the
corresponding iso-imides in the presence of esters of acid
halides, such as ethyl chloroformate.
These known processes are relatively involved and in
some cases also require expensive dehydrating agents. Above
all, however, with these processes considerable amounts of one
or more by-products are obtained, the working up of which, if
it is possible at all, is very laborious and costly. Finally,
the elimination, in a manner which meets the current regulations
for environmental protection, of by-products which cannot be
~.
~L~8~937
utilised again, for example the elimination of the salts
obtained when the reaction is carried out in the presence of
acetyl chloride, acetic anhydride or trifluoroacetic anhydride
and a tertiary amine, is frequently problematical and extremely
expensive.
It has now been found that it is possible, whilst
avoiding the abovementioned disadvantages, to manufacture iso-
imides of the formula
. _l _
A / C \O (I)
\C/
_ _ _ Q
n
or mixtures of iso-imides of the formula I and imides of the
formula Ia
l A/\ N -1 Q (In)
lCI/
. O n
in which A represents -CH=CH- or ~ , n represents the number
1 or 2 and, when n = 1, Q represents an unsubstituted or substi-
tuted aryl group, and when n = 2, Q represents an unsubstituted
or substituted arylene group or a group of the formulae
- 3 -
1~84937
in which X denotes the bridge member -O-, -S-, -S-S-, -S02-,
-CH2-, -CO- or CH~
--C--
IH3
and the substituents on the aryl or arylene groups Q are free
from acid hydrogen atoms, in a simple, economical manner and in
good to very good yields by reacting an amide-acid of the for-
mula II
~ OOH
A .
CO~ v _ Q (II)
n
in which that stated under formula I applies in respect of A, Qand n, with ketene at a temperature of about -10C to +80C.
A pre~erably represents -CH=CH-.
The aryl or arylene groups represented by Q are, in parti-
cular, phenyl, l- or 2-naphthyl, phenylene or naphthylene groups,
especially the 1,3- or 1,4-phenylene group and 1,2-, 1,8- or Z,3-
naphthylene group. Groups of this type can be unsubstituted
or substituted. Possible substituents on the aryl or arylene
groups Q which are free from acid hydrogen atoms are, for
example, those which follow: halogen atoms, for example F, Cl,
Br and I; alkyl groups, especially those with 1-8 carbon atoms;
halogenoalkyl groups with 1-3 carbon atoms, such as the tri-
fluoromethyl groups; alkylthio and N,N-dialkylamino groups,
each with, preferably, 1-4 carbon atoms in the alkyl parts;
-- 4 --
~084937
alkoxy groups, above all those with 1-4 carbon atoms; phenoxy
groups; alkoxycarbonyl and alkanoyl groups with, preferably,
2-5 carbon atoms, such as the methoxycarbonyl, ethoxycarbonyl
and n-butoxycarbonyl group and the acetyl and propionyl group;
phenylsulphonyl and alkylsulphonyl groups, the latter prefer-
ably containing 1-4 carbon atoms; and cyano and nitro groups.
Aryl and arylene groups Q can contain 1 to 3, and pre~erably 1
or 2, substituents of this type. When n = 1, Q preferably
represents the 1- or 2-naphthyl group or a phenyl group which
is substituted by one or two halogen atoms, especially chlorine
atoms, one or two alkyl groups, each with 1-4, and especially
1 or 2, carbon atoms in the alkyl parts, or a trifluoromethyl,
nitro or cyano group. When n = 1, Q particularly preferen-
tially denotes an unsubstituted phenyl group.
If n denotes the number 2, Q preferably represents the
1,3-phenylene group or 4,4'-diphenyl ether group, but above all
the 4,4'-diphenylmethane group.
If the group Q has highly electronegative substituents,
such as halogen atoms or nitro, cyano, alkyl or phenylsulphonyl
groups, it is possible, depending on the position of these sub-
stituents on the radical Q, for relatively small or relatively
large amounts of the corresponding imides of the formula Ia
also to be formed, in addition to the iso-imides of the ~ormula
I, by the process according to the invention. The group Q
therefore preferably has at most 2 of the highly electronegative
substituents mentioned.
~ he reaction according to the invention is advantageously
- -` 108~937
carried out in the presence of an organic solvent which is inert
under the reaction conditions. Examples of suitable solvents
are optionally chlorinated aromatic hydrocarbons, such as ben-
zene, toluene, xylenes and chlorobenzene, chlorinated aliphatic
hydrocarbons, such as chloroform, methylene chloride and 1,2-
dichloroethane, aliphatic and cycloaliphatic ketones, such as
acetone, methyl ethyl ketone and cyclohexanone, and also ali-
phatic and cyclic ethers, such as diethyl ether and dioxane.
Particularly preferentially, the reaction is carried out in
acetic anhydride, on the one hand because particularly high
yields are achieved by this means and on the other hand because
the acetic anhydride formed during the reaction with the ketene
can, after distillation, be re-used for further reactions.
The amide-acids of the formula II are known or can be
manufactured according to methods which are in themselves known,
for example by reacting maleic anhydride or phthalic anhydride
with monoamines or diamines of the formula H2N-Q or H2N-Q-NH2
respectively.
The amide-acids of the formula II and ketene are prefer-
ably employed in a stoichiometric amount, that is to say when
n = 1, the amide-acid of the formula II and ketene are prefer-
ably employed in a molar ratio of 1:2, whilst when n = 2, the
molar ratio of the amide-acid of the formula II to ketene is
advantageously 1:4. However, it is also possible to use a
small excess of one or other of the reactants, for example to
use an up to about 10% strength molar excess of the amide-acid
o~ the formula II or ketene.
iO84937
The acetic anhydride formed during the reaction can,
as already mentioned, be recovered in a very simple manner by
means of distillation and optionally re-used for further reac-
tions.
The preferred reaction temperatures are between about
0 and f60C. After the reaction has ended, the iso-imides
of the formula I, or the mixtures of iso-imides of the formula
I and imides of the formula Ia, can be isolated, and optionally
purified, in a manner which is in itself known, for example by
filtration, distillation and/or evaporation and subsequent
washing with sodium bicarbonate solution and water or recry-
stallisation from suitable solvents, such as toluene, cyclo-
hexane, acetone and methyl ethyl ~etone.
Iso-imides which can be manufactured by the process
according to the invention are in themselves known. N-
substituted isomaleimides and N,N'-disubstituted bis-isomale-
imides or bis-isophthalimides can be reacted with diamines, for
example by the methods described in U.S. Patent Specifications
2,980,701, 2,995,577, 2,998,429, 3,035,065 and 3,144,435 and
Journal of Polymer Science: Polymer Chemistry Edition, 13,
1,691-1,698 (1975), to give linear polymers. N-substituted
isophthalimidesareused, for example, as intermediate products
for the manufacture of pharmaceuticals [compare, for example,
J. Med. Chem., 10, 982 (1967)]. Iso-imides of the formula I,
wherein A represents the group -CH=CH-, can also be used as
fungicides or defoliating agents.
Finally, the iso-imides of the formula I manufactured
-- 7 --
iC~84937
according to the invention can also be isomerised in a manner
which is in itself known to the corresponding imides of the
formula Ia, for example by treating them with catalytic amounts
of an alkali metal salt or ammonium salt of lower fatty acids,
such as sodium acetate (see, for example, U.S. Patent Specifi-
cation 2,980,694). The imides of the formula Ia, in turn,
are used, inter alia, as insecticides and/or for the manufacture
of polymers.
Example l
OOH ~
+ 2 C~2=C=0 ~ 0 + (CH3C0)20
19.2 g (0.1 mol) of N-phenylmaleamic acid are suspended
in 100 ml of acetic anhydride. Using a heating bath, the
suspension is warmed to 45C, whilst stirring, the heating bath
is then removed and about 0.2 mol of ketene are passed into the
suspension. The temperature then rises to 50-52C and a
clear yellow solution forms. This solution is concentrated
in a rotary evaporator. The residual yellow oil is poured
onto ice water. The precipitate hereupon formed is filtered
off, washed with saturated sodium bicarbonate solution and water
and dried in vacuo over phosphorus pentoxide. This gives
16.0 g (92% of theory) of N-phenyl-isomaleimide; melting point
58-61C.
I~ spectrum (CHC13): Ama~ inter alia 5.55/5.95 ~.
Analysis for ClO~ N~2 (molecular weight 173.17):
1()84937
calculated: C 69.36% H 4.08% N 8.0~/o
found: C 69.37% H 4.24% N 8.04%
The acetic anhydride recovered when the solution is
concentrated can be re-used after distillation.
Example 2
OOH HOOC
O~H ~ C~2 ~ NHOC 3 ~ 4 Cl~2=C-
+ 2 (~H3C0~20
N~CH2~N' ' .
~ 0 g (0.2 mol) of N,N'-4,4'-diphenylmethane-bis-male-
amic acid are suspended in 600 ml of acetic anhydride, the
suspension is heated to 45C, whilst stirring, and 0.8 mol of
ketene are passed in without heating. The temperature then
rises to 49-50C. An almost clear yellow-orange solution
forms and this is filtered whilst it is still warm The fil-
trate is concentrated in a rotary evaporator to about 1/~ of
its original volume. The reaction product is then allowed
to crystallise out in a refrigerator, the mixture is filtered
and the residue is washed with saturated sodium bicarbonate
solution and water. The resulting yellow c~ystals are dried
in vacuo. This gives 56.7 g (7~/0 of theory) of N,N'-4,4'-
diphenylmethane-bis-isomaleimide; melting point 154-155C.
_ g
~084937
IR spectrum (CHC13): AmaX inter alia 5.55/5.95 ~.
Analysis for C21H14N204 (molecular weight 358.~5):
calculated: C 70.39% H 3.94% N 7.82%
found: C 70.34% H 3.95% N 7.650/o
The acetic anhydride recovered can be re-used after
distillation.
Example 3
N ~ CH3
Analogously to the process described in Example 1,
10.3 g (0.05 mol) of N-p-tolylmaleamic acid in 75 ml of acetic
~nhydride and 0.1 mol of ketene give 8.6 g (92% of theory) of
N-p-tolyl-isomaleimide with a melting point of 71-73C.
IR spectrum (CHC13): AmaX inter alia 5.59/5.99 ~.
Analysis for CllHgN02 (molecular weight 187.20):
calculated: C70,58% H 4.85% N 7.48%
found: C70.67% H 4.77% N 7.53%
Example 4 0
~b
C~
Analogously to the process described in Example 1,
26.0 g (0.1 mol) of N-3,5-dichlorophenylmaleamide in 200 ml
of acetic anhydride and 0.2 mol of ketene give 23.1 g (95% of
. -- 10 --
- ~84937
theory) of N-3,5-dichlorophenyl-isomaleimide; melting point
82-85C.
IR spectrum (Nujol): ~max inter alia 5.55/5.80 ~.
Analysis for CloH5C12N02 (molecular weight 242.06):
calculated: C 49.62% H 2.08% N 5.79% Cl 29.2~,~
found: C 49.26% H 2.21% N 5.670/o Cl 28.750,6
Example 5
~0 + ~\N~No2
Analogously to the procedure described in Example 1,
about 0.08 mol of ~etene are introduced into a suspension of
10.0 g (0.042 mol) of N-p-nitrophenylmaleamic acid in 75 ml of
acetic anhydride. This gives 8.6 g (94% of theory) of the
reaction product which, according to the IR spectrum and NMR
spectrum, consists of a mixture of N-p-nitrophenyl-maleimide and
N-p-nitrophenyl-isomaleimide; melting point 97-150C.
IR spectrum (CHC13): ~max inter alia 5.48/5.54/5.90 ~ (iso-imide);
5.78 ~ (imide).
Analysis for CloH6N204 (molecular weight 218.17):
calculated: C 55.05% H 2.77% N 12.84%
found: C 54.75~0 H 2.78% ~ 12.8~/o
Example 6
N ~ Cl
- 1084937
Analogously to the procedure described in Example 1,
0.6 mol of ketene is passed into a suspension of 67.5 g (0.
mol) of N-p-chlorophenylmaleamic acid in 600 ml of acetic
anhydride. This gives 59.4 g (95% of theory) of the
reaction product which, according to the IR spectrum, consists
in the main of N-p-chlorophenyl-isomaleimide and in small pro-
portions of N-p-chlorophenyl-maleimide; melting point 85-95C.
IR spectrum (CHC13): ~max inter alia 5.55/5.95 ~ (iso-imide);
5.70 ~ (imide).
Analysis for CloH6ClN02 (molecular weight 207.62):
calculated: C57.85% H 2.91% N 6.75% Cl 17.08%
found: C57.63% H 3.02% N 6.~2% Cl 17.03%
Example 7
~ Jo
r~ o~
N ~ 0 ~ ~
40 g (o.i mol) of N,N'-(4,4'-diphenyl ether)-bis-
maleamic acid are suspended in 400 ml of acetic anhydride.
The suspension is warmed to 45C, whilst stirring. Sub-
sequently, the heating is removed and 0.4 mol of ketene is
passed in. The temperature then rises to 52C. An
orange-yellow suspension is obtained and this is filtered
whilst still warm (conversion 88%; 5 g of residue consisting
of unconverted bis-maleamic acid3. The filtrate is concen-
trated to dryness in a rotary evaporator at a bath te~r.-ra.;ure
o~ 60C.
~084937
The residue is suspended in 100 ml of diethyl ether,
the suspension is filtered and the product is rinsed with 20 ml
of diethyl ether and dried in vacuo over potassium hydroxide.
This gives 25.5 g (80% of theory, based on an 88% conversion)
of orange-yellow N,N'-(4,4'-diphenyl ether)-bis-isomaleimide;
melting point 155-159C.
IR spectrum (CHC13): A~aX inter alia 5.55/5.95 !1-
Analysis for C20Hl2N2o5 (molecular weight 360.33):
calculated: C 66.670~ H 3.36% N 7.78%
found: C 66.14% H 3.51% N- 7.690/o
Example 8
n
,COOH HOOC
i ~ ~ 4 CH2=c=o ~ ~ ~0 ~¦ ~ 2 (CH3CO) 2
~CONH ~ N~OC' ~ ~
Analogously to the procedure described in Example 7,
30.4 g (0.1 mol) of N,N'-1,3-phenylene-bis-maleamic acid in
400 ml of acetic anhydride and 0.4 mol of ketene give 22.0 g
(82% of theory) of N,N'-1,3-phenylene-bis-isomaleimide;
melting point 172-177C.
IR spectrum (CHC13): i~maX inter alia 5.55/5.95 ~.
Analysis for C14H8N204 (molecular weight 268.23):
calculated: C 62.690~o H 3.01% N 10.44%
found: C 62.29% H 3.02% N 10.60%
-- 13 --
.
iO8~937
Example 9
0 ~ + ~ ~ 52 ~ - ~
40.5 g (0.091 mol) of N,N'-4,4'-diphenylsulphone-bis-
maleamic acid are suspended in 400 ml of acetic anhydride.
Using a heating bath, the resulting suspension is warmed to
45C, whilst stirring, the heating bath is then removed and
0.4 mol of ketene is passed into the suspension. The
temperature then rises to 48C. Unconverted amide-acid
(0.500 g, that is to say 99% conversion) is removed by filter-
ing off and the filtrate is evaporated in a rotary evaporator.
The yellow solid residue is suspended in saturated sodium
bicarbonate solution, the suspension is filtered and the pro-
duct is rinsed with water. After drying in vacuo at 20-
25C, this gives 34.8 g (95% of theory) of a product which,
according to the IR spectrum, consists in the main of N,N'-
4,4'-diphenylsulphone-bis-maleimide and in smaller proportions
of N,N'-4,4'-diphenylsulphone-bis-isomaleimide; melting point
195-205~.
IR spectrum (CHC13): AmaX inter alia 5.55/5.90 ~ (iso-imide);
5.80 ~ (imide).
Analysis ~or C20H12N206~ (molecular weight 408.38):
calculated: C 58 82% H 2.96% N 6.86% S 7 . 85%
- ~4 -
~' '
1084937
found: C 58. 62% H 3.18% N 6 . 66~o S 7 . 76%
Example 10
40 g (0.1 mol) of N,N'-4,4'-diphenylmethane-bis-male-
amic acid are suspended in 150 ml of acetone. 0.4 mol of
ketene is passed in at 35C. The resulting yellow suspen-
sion is filtered (15.2 g of residue consisting of unconverted
bis-maleamic acid, conversion = 62C~)~ the filtrate is poured
onto ice water and the precipitate is filtered off, washed with
saturated sodium bicarbonate solution and finally dried in
vacuo at 20-25C. This gives 20.8 g (92% of theory, based
on a 62% conversion) of N,N'-4,4'-diphenylmethane-bis-iso-
maleimide.
IR spectrum (CHC13): ~max inter alia 5.55/5.95
Example 11
2 CH2-C=O--~ ~ + (CH3CO)2O
`CON~ ~ CH3 . ~ ~ H3
25.6 g (0.1 mol) of N-p-tolyl-phthalamic acid are sus-
pended in 250 ml of acetic anhydride at 20-25C. 0.2 mol
of ketene is then passed in and the temperature rises to 33C.
A clear, pale yellowish solution forms and is concentrated in
vacuo in a rotary evaporator (bath temperature 60C) and the
residue is suspended in saturated sodium bicarbonate solution,
the suspen~ion is filtered and the product is washed with water.
After drying in vacuo at 40C, this gives 21.0 g (88% of theory)
of ~-p-tolyl-isophthalimide; melting point 116-11~C.
- 15 -
1~84937
IR spectrum (CHC13): AmaX inter alia 5.55/5.85 ~.
Analysis for C15HllN02 (molecular weight 237.26):
calculated: C 75.94% H 4.67% N 5.91%
found: C 75.64% H 4.65% N 6.01%
Example 12
COOH
+ 2 CH2-C=0 ---~ + (C~3CO)20
CH3
100.1 g (0.457 mol) of N-(2,6-dimethylphenyl)-maleamic
acid are suspended in 750 ml o~ acetic anhydride. Using a
heating bath, the suspension is warmed to 30C, the heating
bath is then removed and about 0.9 mol of ketene is passed into
the suspension, whilst stirring. The temperature then rises
to 40C and a yellow homogeneous solution forms. The acetic
anhydride is removed in a rotary evaporator, the residue is
taken up in benzene and the solution is washed with saturated
sodium bicarbonate solution and water, dried and evaporated in
a rotary evaporator. This gi~es 90.4 g (98% of theory) of
deep yellow crystalline N-(2,6-dimethylphenyl)-isomaleimide
~rith a melting point of 60-62C.
TR spectrum (CHC13): AmaX inter alia 5.50/5.55/5.90 ~.
Analysis f~r C12HllN02 (molecular weight 201.23):
calculated: C 71.63% H 5.51% N 6.96% 0 15.90%
found: C 71.45% H 5.59% N 7.2~,~ 0 15.9
- 16 -
