4,4'-difluorobenzophenone synthesis method

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for synthesis of 4,4'-difluorobenzophenone, the main raw product for synthesis of aromatic polyester-ketones. The method involves a first step where fluorobenzene reacts with formaldehyde under conditions for catalysis with organic sulphonic acids to form difluorodiphenylmethane. The product is extracted and oxidised with nitric acid at the second step to 4,4'-difluorobenzophenone.

EFFECT: invention enables to obtain the end product using a simple and efficient method.

5 cl, 1 ex

The present invention relates to a method for producing 4,4'-diftorbenzofenon and its isomers. 4,4'-differentfrom (4,4'-DFBP) is the main source for obtaining aromatic polyetherketones. They are high-quality plastics with the ever-increasing annual production volume, so that annually produced worldwide amount of 4,4'-DFBP is in a state of growth. The most important polyetherketone are polyetheretherketone (PEEK) and polyetherketone (PEK). They are characterised by a melting point above 330°C, and high chemical resistance. Small amounts are used for the provision of drugs and chemicals for agriculture.

Currently, 4,4'-DFBP get almost exclusively in the following two-step synthesis according to the patent US-A-2,606,183 (1952) and US-A-2,705,730 (1955), both belong to the Head and others: first, 4,4'-diaminodiphenylmethane (MDA means methylenedianiline) diasterous through NaN₂in acidic solution of HF and, according to Balz-Shiman, using HBF₄fluoride ion is introduced into aromatic compounds with excretion of N₂(see Beyer, Walter, Lehrbuch der organischen Chemie, Hirzel, 24. Edition, 2004, page 626, and Balz, Schiemann, Berichte, Vol 60, p. 1186 (1927)). The resulting 4,4'-defenitelly (DFDPM) after cleaning oxidized by HNO₃.

According to the documents EP-A-0004710 (Staniland and others (1979)) and US-A-2,563,796 (Shenk and other) which you can also directly decomposing fluoride, page, dissolved in hydrofluoric acid, by heating.

The second method of synthesis of benzophenone is the acylation according to Friedel-Crafts, which is carried out either directly from fervently and phosgene according to US-A-4,618,762 (Desbois (1986)), in hydrofluoric acid and boron TRIFLUORIDE as a catalyst, or, according to US-A-4,814,508 (Gors and others (1989)), from fervently and chloride 4-fermenting acid with aluminofluoride and literorica as catalysts.

The third possibility of the synthesis is the nucleophilic substitution of aromatic compounds (SNAr). The fluorine atom substituted or nitro-group (US-A-6,274,770, Clarc and others, 2001) in the presence of Tetramethylammonium as a catalyst for the phase transition (PTC), or halide (JP-A-57169441) in the presence of potassium fluoride at elevated temperatures (150-200°C). Another possibility to obtain 4,4'-differentfrom described in JP-A-61221146 (Fukuoka and others, 1986). Torbenson using a catalyst based on noble metals result in a reaction in the autoclave with carbon monoxide and oxygen.

In the document DE-A-698 15 082 describes the synthesis of 4,4'-dinitrodiphenylamine. Is the air oxidation in dimethylacetamide; after this the nucleophilic substitution of aromatics using Tetramethylammonium as a catalyst for the phase transition. The yield is about 70%. The reaction is carried out with 60 mg of IP is one substance in 10 ml of solvent, so it is not a process, suitable for industry.

In the document US-A-4,978,798 describes a multistage expensive method in which first, in the presence of Lewis acid, trihalomethanes result in reaction with halogenatom containing at least 2 chloride Deputy. Educated biphenyldicarboxylic handle then with water, and formed halogenation. After that, the chloride substituents in 2 stages displace fluoride.

Lasting several decades, the search for various synthesis methods to obtain diftorbenzofenon shows that none of these methods are not free from serious shortcomings.

In the variant with acylation reaction Friedel-disadvantage is first of all a big need for catalysts and their disposal. In the case of the reaction of Balsa-Shiman problem is primarily a solvent (hydrofluoric acid) and costly cleanup terraforming acid. In addition, the formation of large amounts of inorganic salts.

Nucleophilic substitution to obtain diftorbenzofenon to date have not received any technical value. 4,4'-dichlorobenzophenone as starting material is expensive and, in fact, only transfers the problem to obtain double-para-substituted benzophenone. Wisweb is given of 4,4'-dinitrobenzophenone nitro form nitrites, when used temperatures and economically feasible concentrations may trigger adverse reactions.

In light of the above-discussed the state of the art before the invention of the task is to develop the following simple method for the synthesis of 4,4'-diftorbenzofenon.

This problem is solved due to the fact that torbenson interacts with formaldehyde under conditions of acid catalysis with the formation of isomeric mixtures of 2,4'- and 4,4'-DFDPM, which is then oxidized to the corresponding benzophenone. Isomers benzophenone separated by recrystallization.

This method provides the following benefits:

1. As in the interaction, and the oxidation with the exception of by-products formed only water and no other by-products that would be in stoichiometric quantities.

2. Both reactions can proceed at normal pressure and temperatures from 0°C to 100°C, which significantly reduces hardware expenses.

3. The acid catalyst can be regenerated by heating in vacuum.

The object of the invention is a method for 4,4'-diftorbenzofenon, characterized in that the first stage in the conditions of catalysis of organic sulfonic acid torbenson result in reaction with formaldehyde education defenitelly obtained product is isolated and on vtoro the stage oxidizes nitric acid to 4,4'-diftorbenzofenon.

After the first stage receive a mixture consisting of about 95% of the isomers defenitelly (DFDPM) and 5% more vysokointensivnykh products.

Educated at this defenitelly consists of approximately 77% of 4,4'-DFDPM and 23% of 2,4'-DFDPM. This isomeric mixture by vacuum distillation to separate from by-products, however, cannot be divided into its isomers.

After the first stage, the organic sulfonic acid is separated and recovered.

Excess torbenson before vacuum distillation also separated from DFDPM.

Florasol is a good source material for fluorine-containing organic compounds, as it is an industrial and it is relatively inexpensive.

Torbenson for the first reaction stage is used in excess, and it is also a solvent.

The more diluted the solution, the less is formed vysokointensivnykh products per DFDPM.

The molar ratio of fervently to formaldehyde is from 5:1 to 30:1, preferably from 8:1 to 12:1.

Formaldehyde is used preferably as trioxane or as paraformaldehyde. However, you can also enter a dry gaseous formaldehyde.

Organic sulfonic acids, are suitable as catalysts are, for example, methanesulfonate acid, econsultancy acid, triform tursultanova acid, benzolsulfonat acid, m-benzolsulfonat acid, benzene-1,3,5-trisulfonic acid, 2,4-dinitrobenzenesulfonic acid, p-toluensulfonate acid and permentantly acid (FBSA) or naphthalenedisulfonic acid.

FBSA is compared with methanesulfonic acid the advantage that it is soluble in fervently and also at temperatures below 45°C leads to a faster response without adverse shift in the ratio between the isomers from 4,4'-DFDPM to 2,4'-DFDPM that usually happens at high temperatures.

The advantage of FBSA in comparison with p-toluensulfonate acid is that after the first stage reaction of the system do not need to remove any products of the cleavage catalyst.

The use of FBSA as catalyst preferably. FBSA is usually in the form of an isomeric mixture of 4-forbindelsesteknologi acid and 2-forbindelsesteknologi acid.

The reaction temperature in the first stage is usually from -15 to 70°C, preferably from -15 to 45°C, particularly preferably from 0 to 25°C.

In the second stage isomeric mixture DFDPM oxidized with nitric acid at a temperature of from 50 to 130°C, preferably from 65 to 100°C, and the resulting 4,4'-DFBP allocate isomere pure by recrystallization. Separation of the isomers can be performed by recrystallization from a mixture of acetic acid and water is, what is advantageous, both from an economic and from an environmental point of view, because in addition to acetic acid does not need any additional solvents.

According to the following optional form of implementation of the method according to the invention in a second stage of nitrous gases formed during the oxidation with nitric acid, oxidized by molecular oxygen and by analogy with the method of Ostwald water transfer in nitric acid. Can be used as pure oxygen and air.

Further, the method according to the invention is explained in more detail in the examples.

1.1 Reaction fervently with formaldehyde

In fervently dissolve anhydrous FBSA add paraformaldehyde in powder form and stirred for several hours to remove heat of reaction. Is the following reaction:

Torbenson is used in excess and is also a solvent.

The molar ratio of fervently to formaldehyde is from 5:1 to 30:1, preferably from 8:1 to 12:1.

FBSA is a mixture of isomers of 4-forbindelsesteknologi acid and 2-forbindelsesteknologi acid.

Tsepliaeva the reaction of water forms with FBSA insoluble monohydrate.

He begins yet to crystallize after a few minutes of reaction.

This FBSA should be applied in equimolar ratio with p is reformulado, better in small excess.

The colder the solution, the more favorable the ratio of 4,4'-DFDPM to 2,4'-DFDPM. 2,2'-DFDPM not formed.

The temperature ranges from -15 to +70°C, preferably from 0 to 30°C. At the beginning of the reaction is carried out preferably at a lower temperature, end temperature can rise to the speedy completion of the reaction.

1.2 Separation and regeneration of the FBSA

At the end of the reaction is added a small amount of water (about 1 g to 4 g used FBSA).

The crystals liquefy. The acidic phase is deposited. It is separated and again washed with pure florasulam.

Processing FBSA can be accomplished in two ways:

- heating in vacuum up to 140°C, and water are removed almost completely

or

- heating in vacuum up to 120°C within a short period of time, extracting more water-containing solution florasulam and new heating undissolved in fervently faction.

FBSA in the industry is produced by sulfonation of fervently concentrated sulfuric acid.

The sulfonation is a reversible reaction. Therefore, when heated aqueous FBSA is formed a number of fervently, which immediately evaporates, and sulfuric acid. It should be separate, as it is in the anhydrous condition chars paraformaldehyde, pulling the water out of it. This feedback re the Ktsia the stronger, the higher the temperature. Tseplyalsya while torbenson should not be removed from the installation.

This is a significant advantage of FBSA in comparison with p-toluensulfonate acid. Tseplyalsya while toluene has with great difficulty, be removed from the system, otherwise it will react with paraformaldehyde and florasulam with the formation of 4-methyl-4'-fordefinierade.

With careful removal of water the formation of toluene so small, that arise because of this loss in output is negligible. In this case, the application of p-toluensulfonate acid due to its easy availability is preferable FBSA.

1.3 the Department of fervently and vacuum distillation DFDPM

The organic phase is the last phase is first washed at room temperature a small amount of water, and then with a solution of soda, and the basic number of fervently distilled at normal pressure, and the residue is distilled in vacuum at about 25 mbar and a temperature of about 90°C. the Crystals, possibly formed, is filtered by processing the remainder of the soda solution. The filtrate consists of isomers DFDPM and vysokointensivnykh products.

The first is distilled at an absolute pressure of 25 mbar in the temperature range of 130-140°C without separation of the isomers. At these temperatures no vysokokonditsionnymi impurities have not distills.

However, if the temperature in Cuba distilling apparatus will rise to 200°C, these impurities will be present in the distillate.

This little faction you want to distill twice.

VAT product consists of impurities plus approximately 25-35% DFDPM.

1.4 nitric acid Oxidation

Isomeric mixture DFDPM preferably oxidized by HNO₃at temperatures from 65 to 100°C.

A mixture of 102 g (0.50 mol) DFDPM and 500 ml of 65%HNO₃(2.5 mol) warm with stirring at 75°C for 15 hours, with proceeds quantitative oxidation with the formation of nitrous gases. When cooled below 50°C the organic phase solidifies to a waxy mass which is held together in the form of small crystals of 4,4'-DFBP. This mass is separated from the aqueous phase and recrystallized.

According to the following preferred form of implementation of the method according to the invention can, on the one hand, to avoid high demand in nitric acid and, on the other hand, expensive purification of exhaust gases through the connecting absorbency installation. While nitrous gases formed during the oxidation of nitric acid with oxygen as oxidant, again converted to nitric acid.

Further, this variant of the method according to the invention described in the examples.

As oxidation reactor used in the three-neck flask with a thermometer, a stirring and heating.

The second three-neck flask of the same size the RA with a stirrer, cooling and connection filled with oxygen gas cylinder served as the absorber. The gas space of both flasks were connected to each other and formed with a gas cylinder closed system. In addition, they installed two pumps. First pumped nitric acid from the reaction flask in the absorber, the second was pumped nitric acid from the absorber into the flask reactor.

On DFDPM in the reaction flask were poured about a third of the volume of 25%nitric acid and gently stirring his. At this low concentration nitric acid POPs up. In the absorber receives the same amount of nitric acid with an equal concentration. By the beginning of the common gas space of the two flasks filled with pure oxygen. Flask reactor is heated to about 65°C, then heat for 3 hours at about 75°C. the Absorber cooled to about 25°C, intensively stirred to increase the surface between the gas space and the liquid by splashing drops. Formed in the reaction flask nitrous gases into the absorber. In the cold they are oxidized by the oxygen dissolved in the liquid with the formation of nitric acid. This is completely analogous to the formation of nitric acid by the method of Ostwald. Enriched nitric acid is pumped into the reaction flask, and depleted acid with an equal flow rate of perucac the rests of it in the absorber.

In this reaction system consumes oxygen and, in General, does not form any other gas. The oxygen is pumped out of the cylinder attached to until the reaction stops. After all oxidation nitric acid again is available until the next boot, not counting a minimum of losses due to nitration DFDPM.

Nitric acid is diluted only formed during the oxidation of water.

Thus, it acts only as a catalyst for oxidation, which de facto is molecular oxygen.

Upon cooling, the organic phase is cured with getting waxy mass.

1.5 Recrystallization

From waxy mass obtained after oxidation, can be a mixture of glacial acetic acid and water (9:1) as solvent by repeated recrystallization to obtain 4,4'-DFDPM almost any purity. For this purpose, the oxidation product is mixed with half the amount of solvent and heated. At about 80-90°C, the solution becomes homogeneous. Forms during cooling the mixture of crystals and mother liquor, from which by filtration by suction can be obtained crude product purity of about 95%. By collectively triple recrystallization using each time equal to the amount of the solvent can be achieved purity of at least 99,%.

Filtered by suction, the crystals are dried in vacuum at 90°C.

The mother liquor after the first stage of recrystallization evaporated in vacuum for regeneration of the solvent.

1. The way to obtain 4,4'-diftorbenzofenon, characterized in that in the first stage, torbenson result in reaction with formaldehyde under the conditions of catalysis of organic sulfonic acids with the formation of defenitelly formed when the product is isolated and in the second stage are oxidized by nitric acid to 4,4'-diftorbenzofenon.

2. The method according to claim 1, characterized in that for the first stage reaction torbenson used as both the solvent and phthorbenzotephum acid as a catalyst.

3. The method according to claim 1, characterized in that the reaction temperature in the first stage is from -15 to 70°C.

4. The method according to claim 1, characterized in that in the second stage, carry out the oxidation with nitric acid and oxides of nitrogen formed oxidant again converted into nitric acid.

5. The method according to claim 4, characterized in that the oxidizing agent used is oxygen.