Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
;~23S~
Case 4794/4756 WGG/erc April 26, 1984
4,4-DIHALOHEXAHYDROPHTHALIC ANDROIDS AND
4-FLUOROTETRAHYDROPHTHALIC ANDROID,
AND PROCESSES FOR THEIR PREPARATION AND UTILIZATION
BACKGROUND OF THE INVENTION
This invention relates to novel 4,4-dihalohexahydro-
phthalic androids of the formula
e
yoke
F C
and a novel 4-fluoro-192,5,6-tetrahydrophthalic android of
the formula O
I
F C
o
Methods for preparing and utilizing these compounds are also
disclosed.
~Z3S~2~'
Lowe compounds of this invention are useful as
chemical intermediates for the synthesis of various end
products. In particular, 4,4-dihalohexahydrophthalic
android and 4-fluorotetrahydrophthalic android are
useful in the synthesis of 4-fluorophthalic android,
which in turn is useful for the preparation of aromatic
- ether and thither android curing agents, auntie-
dents and polyetherimide polymers. Examples of the
utility of 4-fluorophthalic android and the various
prior art methods for the synthesis thereof are disclosed
in U.S. Patents 3,850,965 and 3,956,321. An alternate
method for synthesizing 4-fluorophthalic android
directly from the 4,4-dihalohexahydrophthalic androids
of the present invention by simultaneous dihedral-
genation and dehydrogenation is disclosed in a commonly
assigned Canadian Patent Application, So 435,958 of
David Y. Tang entitled "Process for the Preparation of
4-Fluorophthalic Android", filed May 9, 1984.
Lowe following U.S. Patents provide further back-
ground relative to the chemistry of cyclic anhydridesand halo-substituted cyclic androids: 1,891,843 to
Skew et at; 2,391,226 to Clifford et at; 2,764,597 to
Barney; 3,240,792 to Patrick et at; 3,346,597 to Acetic;
3,480,667 to Cigarette et at; 3,819,658 to Gormley et at;
4,045,408 to Griffith it at and 4,302,396 to Tsujimoto
et at.
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The preparation of tetrahydrophthalic androids and the
aromatization thereof by dehydrogenation under various
conditions is known in the chemical literature. Skvarchenko et
at., Obshchei Clue_ i, Vol. 30, No. 11, pp. 3535-3541 disclose
the aromatization of chloro-substituted tetrahydrophthalic
android by heating with phosphorus pent oxide. In the
aromatization process described, however, decarboxylation also
occurs with the formation of the corresponding sheller-
substituted Bunsen compound. The preparation of tetrahydro-
lo phthalic acids and androids and various methods for
dehydrogenation and aromatization thereof are reviewed by
Skvarchenko in Russian Chemical Reviews, Nov. 1963, pp.
571-589.
Bergman, J. Amer. Chum. So., 64, 176 (1942) discloses
the aromatization of tetrahydrophthalic android products of
Diels-Alder reactions. The author discloses that
dehydrogenation occurs when the tetrahydrophthalic android
product is boiled in nitrobenzene. However, it is further
disclosed that dehydrogenation does not occur when
p-bromonitrobenzene, p-chloronitrobenzene, or m-dinitrobenzene
in zillion is employed. Moreover, it has been found that when
the dihalohexahydrophthalic androids of this invention are
dehydrogenated in nitrobenzene, a portion of the nitrobenzene
is reduced to aniline. The aniline reacts with the android
group of either the starting material or product to form immediacy
and thus lower the yield of desired product.
~3~-~2~`
The preparation of 1-fluorocycloalkene from the
corresponding 1,1-difluorocycloalkane by reaction with
an hydrous neutral alumina is disclosed in Strobach et at., J.
Org. Chum., Vol. 36, pages 818-820 (1971).
The preparation of 4-fluoro-1,2,3,6-tetrahydrophthalic
android is disclosed in U.S. Patent Thea reference
discloses that this isomer can be prepared by the reaction of
fluoroprene (2-fluoro-1,3-butadiene) with malefic android.
The compound is reported as the hydrolyzed fluorophthalic acid.
It is a principal object of the present invention to
provide novel intermediate compounds which are useful in the
synthesis of 4-fluorophthalic android. It is another object
of this invention to provide a commercially attractive
synthetic route to prepare 4-fluorophthalic android.
lo SUMMARY OF THE INVENTION
In accordance with this invention, novel deluxe-
hydrophthalic androids are prepared by reacting a sheller-
tetrahydrophthalic android with hydrogen fluoride. This
reaction can be illustrated as follows
/ + HO >
d o
where Y is chlorine or fluorine.
~LZ35~
The reaction actually produces a mixture of
4-chloro-4-fluorohexahydrophthalic android and
4,4-difluorohexahydrophthalic android. The relative
proportion of each compound depends on the degree of
fluorination of the substrate. Either or both of these
compounds can be heated in the presence of an effective amount
of basic alumina to prepare an isometric mixture of
4-fluorotetrahydrophthalic androids as follows
O O o
OX I X + ~xc/o
0 ~-~ of I 0
where Y is chlorine or fluorine. In this reaction, the I
isomer of 4-fluorotetrahydrophthalic android is a novel
compound.
Either or both of the 4-fluorotetrahydrophthalic android
isomers can then be aromatized by heating in the presence of a
dehydrogenation catalyst to prepare 4-fluorophthalic android.
Suitable dehydrogenation catalysts include the Nobel metals,
e.g. platinum, palladium, rhodium, ruthenium, and iridium,
nickel, gamma-alumina, chromium oxide, molybdenum oxide,
tungsten oxide, vanadium oxide and rhenium, either supported or
unsupported. The preferred catalyst system is palladium on a
carbon support. The basic aromatization reaction can be
illustrated as follows
F I\ i/ C\
I
F I
o
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DESCRIPTION OF THE PREFERRED EMBODIMENTS
The 4,4-dihalohexahydrophthalic androids of the present
invention are prepared by the reaction of hydrogen fluoride
with 4-chlorotetrahydrophthalic android as follows
/ + HO ` \ / \ " `\
Of I Of I lo
4-chlorotetrahydrophthalic android, a starting material
for reaction I is a commercially available product which can
be conveniently prepared by reacting chloroprene with malefic
android as shown below
Of clue b (2)
Both of the starting materials for reaction (2) are readily
lo available through commercial sources.
Reaction (1) is suitably carried out in the liquid phase
either at atmospheric pressure or under applied or autogenous
pressure, at temperatures ranging from about 0C to about
150C, and preferably from about 20C to about 70C. The
reaction rate is temperature dependent, the lower temperatures
resulting in lower reaction rates.
~3~i~2~'
The molar ratio of reactions, that is HF:4-chlorotetra-
hydrophthalic android, may vary considerably and will
typically be in the range of from about 1.1:1 to about 25:1.
The reaction will occur at lower molar ratios but the
conversion rate will be low. Higher ratios may be employed,
but are generally less economical. When it is desired to
maximize the yield of 4-chloro-4-fluorohexahydrophthalic
android, it is preferred to utilize a ratio of
HF:4-chlorotetrahydrophthalic android in the range of from
about 1.1:1 to about 2:1. When it is desired to maximize the
yield of 4,4-difluorohexahydrophthalic android, it is
preferred to employ a ratio of from about 2:1 to about 25:1.
If it is desired tug maximize the yield of 4-chloro-4-fluoro-
hexahydrophthalic android, it is preferred to carry out the
lo reaction in the absence of a catalyst. If it is desirable to
maximize the yield of 4,4-difluorohexahydrophthalic android
as well as increase the conversion rate, it is preferred to run
the reaction at a temperature of 70C at autogenous pressures of
about 60-65 prig and HF:4-chlorotetrahydrophthalic android
molar ratio of 8:1. The rate of reaction can also be increased
by the use of a Lewis acid catalyst. Typical Lewis acid
catalysts include for example aluminum chloride, antimony
trichloride, antimony pentachloride, antimony trifluoride,
antimony pentafluoride, antimony oxychloride, molybdenum
pentachloride, ferris chloride, ferrous chloride, and the like.
I
-- 8 --
. The crude reaction product of hydrogen fluoride
and 4-chlorotetrahydrophthalic android, in accordance
with the process of this invention, contains a mixture
of the 4-chloro-~-fluorohexahydrophthalic android
and the 4,4-difluorohexahydrophthalic android, the
proportions of each being dependent on reaction con-
dictions as set forth above. I've android products may
be separated and isolated by conventional physical
separation techniques, such as fractional crystallization,
vacuum distillation, or the like.
queue 4,4-dihalohexahydrophthalic androids of this
invention can be used directly to synthesize flyer-
phthalic android in accordance with a process more
fully described in the afore~lnentioned Canadian Patent
Application, SUN. 435,958. Alternatively, the 4,4-
dihalohexahydrophthalic androids can be used to pro-
pare 4-fluorotetrahydrophthalic android, which can
subsequently be used to synthesize 4-fluorophthalic
android as disclosed in more detail herein. The
former process requires fewer processing steps but
results in a lower overall product yield than the
latter process. In any event, the crude reaction
product of hydrogen fluoride and 4-chlorotetrahydro-
phthalic android can be used in either of the alone-
said processes without the need for separation of
individual components. Nevertheless it is preferred
to utilize the process conditions set forth herein-
above to maximize the yield of 4,4-difluorohexahydro-
phthalic android since 4-chloro-4-fluorohexahydro-
phthalic android may yield some 4-chlorophthalic
android in subsequent reactions.
Jo
:~35~
The 4,4-dihalohexahydrophthalic androids may be
hydrolyzed in a conventional manner, such as by treatment with
water, to prepare the corresponding acids, that is,
4-chloro-4-fluorohexahydrophthalic acid and deflower-
hexahydrophthalic acid.
The 494 dihalohexahydrophthalic androids prepared in
accordance with this invention can be heated in the presence of
basic alumina to prepare an isometric mixture of
4-fluorotetrahydrophthalic androids in accordance with the
lo following reaction
Yo-yo\ / at umi no Foe I)
Q-4 I
where Y is chlorine or fluorine. In reaction (3), the I
isomer of 4-fluorotetrahydrophthalic android is a novel
compound. In accordance with accepted nomenclature, this
compound is designated as 4-fluoro-1,295,6-tetrahydrophthalic
lo android.
Reaction I is usually conducted in the liquid phase at a
temperature in the range of from about 150C to about 270C. A
high boiling solvent such as sulfolane is usually employed.
Alternatively, the reaction can be conducted in the vapor
phase, suitably at a temperature of from about 200C to about
~23S4Z~L'
300C. Atmospheric or autogenous pressure conditions can be
employed in either case.
The amount of basic alumina required is generally in the
range of from about 1% to about 120% by weight of reactant, and
preferably from about 5% to about 25% by weight. As is known
to those skilled in the art, basic alumina is a form of alumina
which is devoid of significant amounts of hydrogen ions, and
which can be conveniently prepared by reacting alumina with
sodium hydroxide. The role of the basic alumina in the
reaction is to dehydrohalogenate the 4,4-dihalotetrahydro-
phthalic android substrate.
Separation of the isomers in the reaction product can be
accomplished only with great difficulty due to the similarity
of the isomers in terms of their chemical and physical
properties. However, separation is generally not required or
desirable in many instances.
Heating 4-fluorotetrahydrophthalic android in the
presence of an effective amount of a suitable dehydrogenation
catalyst results in the preparation of 4-fluorophthalic
android. This reaction can be illustrated as follows
F F (4)
or
~\~/ JO
F /
d
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11
Either or both of the 4-fluorotetrahydrophthalic isomers can be
used as starting materials with equal effectiveness. However,
if the isomers are produced concurrently, separation entails
some difficulty. Accordingly, a mixture of isomers is
generally preferred.
Reaction (4) can be conducted in the liquid or vapor
phase. The vapor phase reaction is preferably conducted at a
temperature in the range of from about 200C to about 300C at
atmospheric or reduced pressures.
lo If the reaction (4) is run in the liquid phase, a solvent
such as 1,2,4-trichlorobenzene can be used. If an insoluble
catalyst is employed, it us preferred to utilize the catalyst
in finely divided form, with agitation or stirring to maintain
the catalyst in dispersed form throughout the reaction medium.
The process is preferably run at a temperature of between about
150C and about 400C, and most preferably from about 200C to
about 250C. The process may be run at either atmospheric or
super atmospheric conditions. If the operating temperature is
below the boiling point of the reaction mixture, the reaction
may be run conveniently at atmospheric pressure. However, if
an operating temperature is selected above the boiling point of
the reaction mixture, it is preferred to utilize a sealed
reactor or autoclave and operate at autogenous pressures.
Dehydrogenation catalysts suitable for the process of this
invention include platinum, palladium, rhodium, ruthenium,
iridium, nickel, gamma-alumina, chromium oxide, molybdenum
~Z3~Z~
12
oxide, tungsten oxide, vanadium oxide and rhenium, either
unsupported or on a suitable support. Typical catalyst
supports include for example activated carbon, charcoal,
silicon carbide, silica gel, alumina, acidic silica-alumina,
silica, titanic, zircon, kieselguhr, mixed rare earth oxides,
carbonates, barium carbonate, barium sulfate, calcium
carbonate, pumice, silica alumina mixtures, zealots, and the
like. Suitable catalytic complexes can also be used and
include the My compounds where M is Pod, Pi or Nix and is bound
lo in the structure by phosphine, phosphate or carbamyl lignands.
Complexes of this type are generally soluble in the reaction
mixtures employed in the process of this invention. Typical
complexes include tetrakis(triphenylphosphine)platinum (0);
Bis[(bis(1,2-diphenylphosphino)ethane]palladium (0);
Bis[bis(1,2-diphenylphosphino)benzene~palladium (0);
Tetrakis(triphenylphosphine) nickel (0) and tetrakis(triphenyl-
phosphite)nickel (0).
The following examples are provided to further illustrate
this invention and the manner in which it may be carried out.
It will be understood, however, that the specific details given
in the examples have been chosen for purposes of illustration
and are not to be construed as a limitation on the invention.
In the examples, unless otherwise indicated, all parts and
percentages are by weight and all temperatures are in degrees
Celsius
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13
Examples 1-7 illustrate the preparation of
4,4-difluorohexahydrophthalic android and sheller-
fluorohexahydrophthalic android.
EXAMPLE 1
A motel autoclave was charged with 47 parts of
4-chlorotetrahydrophthalic android and cooled to about -30C.
40 parts of hydrogen fluoride was added and the autoclave was
sealed and heated to about 70~C. The temperature was
maintained at an autogenous pressure of about 60 to 65 prig for
lo about 5.5 hours. The HO was then vented and the reactor purged
with No. The liquid reaction product was dissolved in acetone,
treated with sodium bicarbonate, and the acetone removed by
vacuum distillation. Analysis of the reaction product, using
gas chromatographic techniques, indicated approximately 5.4
percent starting material; ~1.7 percent 4,4-difluorohexahydro-
phthalic android; 0.7 percent 4-chloro-4-fluorohexahydro-
phthalic android, and 0.6 percent of 4,4-dichlorohexahydro-
phthalic android.
EXAMPLES 2-3
The procedure of Example 1 was repeated except that
amounts and conditions were varied as set forth in the table
below:
~2~5~2~
14
Example 2 3
Reaction Tempt (C) 56-57 55-67
Reaction Time (Hours) 27 3.8
Mole Ratio HF:4-chlorotetrahydrophthalic 5:1 10:1
android
Pressure (prig) 110-200 90-200
Product GO Area I)
4,4-difluorohexahydrophthalic android 73.9 83.4
4-chloro-4-fluorohexahydrophthalic android 6.4 6.3
4-chlorotetrahydrophthalic android 6.7 4.1
4,4-dichlorotetrahydrophthalic android 12.5 6.0
EXAMPLE 4
A mixture of 25.0 parts of 4-chlorotetrahydrophthalic
android and 0.80 parts of antimony pentachloride was charged
to a reactor equipped with a cooling condenser and stirrer.
The reaction mixture was maintained at atmospheric pressure and
a temperature of 23C to 40C with stirring, while 39.6 parts
of hydrogen fluoride was added over a period of about one hour.
The reaction mixture was maintained under the same temperature
and pressure conditions, with stirring for an additional 42
hours. The hydrogen fluoride was then removed by evaporation
over a period of about two hours. The reaction mixture was
then heated to about 65-70C, maintained at this temperature
for about two hours, then cooled to room temperature. Analysis
Of the reaction product by gas chromatographic techniques
1~3~4~1
indicated 83.4 percent 4,4-difluorohexahydrophthalic android;
11.2 percent 4-chloro-4-fluorohexahydrophthalic android; 3.6
percent 4-chlorotetrahydrophthalic android.
EXAMPLES 5-7
-
The procedure of Example 4 was repeated except that
catalyst and conditions were varied as shown in the table
below:
Example 5 6 7
Reaction Tempt (C) 24~ 24 24
Total Reaction Time (Hours) 23.6 24.5 23.3
Catalyst SbC15 Mohawk SbF5
(Parts) 3.5 1.7 0.66
4-chlorotetrahydrophthalic 79.6 37.3 18.6
android (parts)
Hydrogen Fluoride (parts) 40.0 20.0 10.0
Mole Ratio HF:4-chlorotetrahydro- 5.0 5.0 5.0
phthalic android
Product GO Area %)
4,4-difluorohexahydrophthalic 13.1 15.0 22.8
android
4-chloro~4-fluorohexahydro- 34.1 26.9 42.0
phthalic android
4-chlorotetrahydrophthalic 42.4 41.1 27.9
android
Other unidentified products 9.9 16.1 7.0
So
16
Examples 8 and 3 illustrate the reaction of
4,4-difluorohexahydrophthalic android with basic alumina in
the presence of palladium or carbon. The reaction was
conducted in the liquid phase using a 1,2,4-trichlorobenzene
solvent. The reaction product contains some 4-fluorophthalic
android in addition to 4-fluorotetrahydrophthalic android
due to the presence of palladium in the reaction mixture.
EXAMPLE 8
A 3-neck flash equipped Whitney a nitrogen inlet, an air
cooled condenser, a thermometer and a magnetic stirrer was
charged with 5.0 grams of 4,4-difluorohexahydrophthalic
android, 0.50 grams of basic alumina, 20.05 grams of
1,2,4-trichlorobenzene and 1.0 grams of 5% palladium on carbon.
The contents of the flask were heated to a temperature of about
195C to 200C for 9.1 hours under a nitrogen blanket.
Analysis of the reaction product, using gas chromatographic
techniques, indicated approximately 42.9 percent
4-fluorotetrahydrophthalic android (both isomers), 36.2
percent 4-fluorophthalic android, 2.3 percent starting
material, and 18.6 percent of other compounds.
~35~2:1~
17
EXAMPLE 9
The procedure of Example 8 was repeated except that the
contents of the flask were changed by decreasing the relative
proportion of basic alumina to starting material. The contents
of the flask were as follows: 1.5 grams of 4,4~difluorohexa-
hydrophthalic android, 0.08 grams of basic alumina, 3.0 grams
of 5 percent palladium on carbon, and 15.0 grams of
1,2,4-trichlorobenzene. The flask was heated to a temperature
of about 195C to 200C for 9.0 hours under a nitrogen blanket.
Analysis of the reaction product, using gas cryptographic
techniques, indicated approximately 12.6 percent 4-fluorotetra-
hydrophthalic android, 47.2 percent 4-fluorophthalic
android, 36.0 percent starting material and 4.2 percent of
other compounds.
