CA1235421A - 4,4-dihalohexahydrophthalic anhydrides and 4- fluorotetrahydrophthalic anhydride, and processes for their preparation and utilization - Google Patents

Abstract

ABSTRACT
4,4-Dihalohexahydrophthalic anhydrides of the formula:

where Y is chlorine or fluorine, are prepared by the reaction of hydrogen fluoride with 4-chlorotetrahydro-phthalic anhydride; the dihalo- anhydrides can be de-hydrohalogenated by reaction with basic alumina to pre-pare a mixture of 4-fluorotetrahydrophthalic anhydride isomers of the formula:

Description

;~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.

~Z35~

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.

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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.

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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 :~35~

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

. 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.

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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) 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 ~L235~

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~

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 ~Z354Z~

Examples 1-7 illustrate the preparation of 4,4-difluorohexahydrophthalic android and sheller-fluorohexahydrophthalic android.

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.

The procedure of Example 1 was repeated except that amounts and conditions were varied as set forth in the table below:

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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 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.

-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 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.

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~

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.

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

A 4,4-dihalotetrahydrophthalic anhydride of the formula where Y is chlorine or fluorine.

The compound of Claim 1 wherein Y is chlorine.

The compound of Claim 1 wherein Y is fluorine.

A 4,4-dihalocyclohexanedicarboxylic acid of the formula where Y is chlorine or fluorine.

The compound of Claim 4 wherein Y is chlorine.

The compound of Claim 4 wherein Y is fluorine.

A process for the preparation of 4,4-dihalohexahydro-phthalic anhydrides of the formula which comprises reacting hydrogen fluoride with 4-chlorotetra-hydrophthalic anhydride of the formula The process of Claim 7 wherin the molar ratio of HF :
4-chlorotetrahydrophthalic anhydride is from about 1.1:1 to about 25:1.

The process of Claim 8 wherein the molar ratio of HF :
4-chlorotetrahydrophthalic anhydride is from about 2:1 to about 25:1.

The process of Claim 7 which is conducted in the liquid phase at a temperature of from about 0°C to about 150°C.

The process of Claim 10 which is conducted in the liquid phase at a temperature of from about 20°C to about 70°C.

The process of Claim 7 which is conducted at about atmospheric pressure.

The process of Claim 7 which is conducted at autogenous pressure.

The process of Claim 7 which is conducted in the presence of a Lewis Acid catalyst.

The process of Claim 14 wherein the catalyst is antimony pentafluoride.

The process of Claim 14 wherein the catalyst is antimony pentachloride.

The process of Claim 14 wherein the catalyst is molybdenum pentachloride.

4-fluoro-1,2,5,6-tetrahydrophthalic anhydride.

A process for the preparation of 4-fluorotetrahydro-phthalic anhydrides of the formula comprising reacting a 4,4-dihalohexahydrophthalic anhydride of the formula where Y is chlorine or fluorine, with an effective amount of basic alumina .

The process of Claim 19 wherein Y is fluorine.

The process of Claim 19 wherein Y is chlorine.

The process of Claim 19 wherein the basic alumina is present in an amount of from about 1% to about 120% by weight of 4,4-dihalohexahydrophthalic anhydride.

The process of Claim 22 wherein the basic alumina is present in an amount of from about 5% to about 25% by weight of 4,4-dihalohexahydrophthalic anhydride.

The process of Claim 19 which is conducted in the liquid phase at a temperature in the range of from about 150°C to about 270°C.

The process of Claim 19 which is conducted in the vapor phase at a temperature in the range of from about 200°C to about 300°C.

The process of Claim 19 which is conducted at about atmospheric pressure.

The process of Claim 19 which is conducted at autogenous pressure.

28. A process for the preparation of 4-fluoro-phthalic anhydride which comprises heating a 4-fluoro-tetrahydrophthalic anhydride of the formula:

or a mixture thereof, in the presence of an effective amount of a dehydrogenation catalyst.
29. The process of claim 28, which is conducted in the liquid phase at a temperature of from about 150°C
to about 400°C.
30. The process of claim 29, which is conducted in the liquid phase at a temperature of from about 200°C to about 250°C.
31. The process of claim 28, which is conducted in the vapor phase.
32. The process of claim 28, which is conducted in a solvent.
33. The process of claim 32, wherein the solvent is 1,2,4-trichlorobenzene.

The process of Claim 28 which is conducted at about atmospheric pressure.

The process of Claim 28 which is conducted at autogenous pressure.

The process of Claim 28 wherein the catalyst is palladium on a carbon support.

37. A fluoro compound of formula (I):

(I) wherein:
Y is chlorine or fluorine; R and Rl are each -COOH or together form an anhydride moiety, and L and M are both hydrogen, or when R and Rl together form an anhydride moiety, Y and one of L
and M may together represent a bond, the other of L and M being hydrogen.

38. A process for the preparation of a compound of formula (I), as defined in claim 37, wherein R and Rl together form an anhydride moiety comprising:
a) when Y is F or Cl and L and M are hydrogen, reacting hydrogen fluoride with 4-chlorotetrahydro-phthalic anhydride, or b) when Y and one of L and M together represent a bond, and the other of L and M is hydrogen reacting a 4,4-dihalohexahydrophthalic anhydride in which the halo groups are selected from chlorine and fluorine, with an effective amount of basic alumina.