DE1095281B - Process for the preparation of heterocyclic dicarboxylic acids or of mixtures of heterocyclic di- and tricarboxylic acids - Google Patents

Description

Process for the production of heterocyclic dicarboxylic acids or of mixtures of heterocyclic di- and tricarboxylic acids It has been found that the alkali salts of carboxylic acids, the carboxyl groups of which are heterocyclic Ring systems of aromatic character are available by heating to temperatures can rearrange between 275 and 5000 C.

Heterocycles with an aromatic character are 5- and 6-membered heterocycles with conjugated double bonds, e.g. B. furan, thiophene, pyrrole, α-pyran, α-thiopyran and pyridine. The heterocyclic rings can be aromatic with other hetero rings Structure or with aromatic rings, preferably with benzene rings, fused be. Such heterocycles are z. B. quinoline, isoquinoline or indole, but also Alkali salts of other heterocyclic carboxylic acids, e.g. B. of benzotriazole or of benzimidazole can be used.

The rearrangement that takes place in the reaction according to the invention consists in a change in position of the carboxyl groups converted into salt form, which can take place both within a molecule and between several molecules. If one starts out from monocarboxylic acids, then mainly disproportionation takes place, with 2 molecules of monocarboxylic acid being disproportionated into 1 molecule of dicarboxylic acid and 1 molecule of the carboxyl-free heterocyclic compound, while during the processing of dicarboxylic and polycarboxylic acids, changes in position of the carboxyl groups and decarboxylation occur. In the case of mononuclear ring systems, the carboxyl groups migrate preferably in the 2,5-position, both in the case of 5- and 6-membered heterocycles. In the case of 6-membered heterocycles, the 2,4,6 configuration is also preferred. In the case of furan-2-carboxylic acid, which is derived from a S-membered heterocycle with a hetero atom, the reaction proceeds according to the following formula: in which Me represents an alkali metal. In the case of pyridine-3-monocarboxylic acid, which is derived from a 6-membered heterocycle with one heteroatom, the reaction proceeds according to the following formula: The main product obtained is the alkali metal salt of isocinchomeronic acid (pyridine-2,5-dicarboxylic acid). The salt of trimesitic acid (pyridine-2,4,6-tricarboxylic acid) can be formed as a by-product.

The alkali salts of mono-, di- and polycarboxylic acids serve as starting materials of the heterocycles mentioned, preferably the salts of sodium and potassium. the end economic considerations one will of the use of rubidium and cesium salts, which in themselves also deliver useful results, refrain. Provided Alkali salts of di- or tricarboxylic acids of mononuclear 6-membered heterocycles as starting material are used, preference is given to using those in which the salts are converted Carboxyl groups not in 2.5 or

2,4,6 position. Serve alkali salts of dicarboxylic acids of S-membered heterocycles as starting materials are preferably processed Salts of those acids whose carboxyl groups are not in the 2,5-position.

Instead of the alkali salts you can also process mixtures of them the salts form, e.g. B. the free ones Acids, their chlorides or Anhydrides and alkali carbonates Mixtures of several carboxylic acids can also be processed be, whereby in the case of the simultaneous processing of carboxylic acids, the does not contain the same number of carboxyl groups in the molecule, the mixing ratio can be adjusted so that the amount of present in the reaction mixture per hetero ring system Carboxyl groups of the gross composition of the carboxylic acid desired as the end product is equivalent to.

This mixing ratio can be in the range from two to there are three carboxyl groups per hetero ring system. Do you want to z. B. pyridinedicarboxylic acid received as the main product, so you go z. B. from a mixture in the existing Pyridine mono- and tricarboxylic acids are present in an equimolecular ratio. Want to promote the formation of pyridinetricarboxylic acids, you can, for. B. equimolecular Use amounts of pyridine di- and tetracarboxylic acids.

The carboxylic acid salts to be processed are preferably in as possible processed dry. If the salts are present as an aqueous solution, so can they are made by methods known per se, preferably by spray drying, Convert into dry powder and, if necessary, to remove small residues dry in moisture in a manner known per se.

With some compounds, the reaction occurs as soon as they are heated Temperatures of over 2750 C in progress. The maximum temperature is to be regarded as in which the reaction product shows noticeable decomposition.

As a rule, temperatures of 50 ° C. should not be exceeded. The optimum reaction temperature differs from case to case. Often it lies the optimum temperature range for the reaction is 20 to 400 C below the melting temperature of the salt at normal pressure. For example, pyrogenic potassium melts under normal pressure at 350 to 360 "C; the optimum reaction temperature for the present reaction in this case is 320 to 330 "C. Thiophene-2-carboxylic acid potassium melts at Normal pressure very imperfect at 4200 C; its optimal reaction temperature is at 3700 C. The optimal reaction temperature is for potassium pyrrole-2-carboxylic acid also below the melting point, which is 3400 C. In general, the optimal temperature in the range of 330 to 450 "C. In this temperature range it is the reaction mixture is sometimes more or less liquid, which makes the work under Moving the reaction mixture (e.g. with the help of a stirrer or roller autoclave) is facilitated. The reaction mixture can be finely divided by inert fillers such as sand Diluted coke or other forms of carbon, metal powder, chips or pieces will.

In addition, alkali carbonates or bicarbonates are used as diluents suitable.

It has been found that the reaction is particularly effective at elevated pressure runs well, which is advantageously generated by inert gases. Serve as inert gases especially nitrogen and carbon dioxide. The level of pressure during the reaction can vary within wide limits and be, for example, 10 atm or more. Appropriately the reaction vessel is placed under the pressure of an inert gas before heating. When heated, the pressure rises and during the reaction, for. B. 15 to 250 atm be. You can also generate the pressure by removing the carboxyl group-free heterocyclic compound, such as. B. pyridine, adds.

It has also been shown that the reaction through presence is favored by catalysts. The metals zinc, cadmium, Mercury or lead or their compounds, e.g. B. the Oxides, hydroxides, bicarbonates, Carbonates, fluorides, chlorides, bromides, iodides, sulfates, nitrates or other salts inorganic acids; you can also process salts of organic acids, z. B. the formates, acetates, propionates, stearates, oleates, ricinoleates, benzoates, phthalates. Above all, however, the catalytically active metals can also be in the form of their salts be used with the heterocyclic carboxylic acids to be processed. The amount of the metal can vary within very wide limits and up to 150%, preferably 0.5 to 5 percent by weight, based on the reaction mixture. The catalysts can be particularly fine in the reaction mixture or in the starting material distribute that one is an aqueous solution of the alkali metal salts serving as starting material heterocyclic carboxylic acids, which contains the catalysts dissolved or suspended, converted into a dry powder by atomization or on drum dryers. the Free metals can conveniently be used in such a way that a reaction vessel used, which is coated with a layer of catalytically active metal.

The rearrangement can lead to partial decarboxylation with regression of the heterocyclic ring system. The heterocycles formed can be z. B. win if you relax the autoclave via a cold trap.

To work up the reaction mixture, it is dissolved in water and by filtering off or by treatment with activated charcoal or other decolorizing agents freed from unwanted components. The heterocyclic ones formed in the rearrangement Carboxylic acids are usually less soluble in water than the starting materials, therefore they can be made by acidifying the aqueous solution with acids, such as mineral acids or organic acids, and easy to crystallize from the remaining ingredients Separate the reaction mixture, in particular from unreacted starting materials. If desired, the acid can now act on its derivatives, in particular its chlorides or esters, are processed, in the case of the esters, the esters of methyl or Ethyl alcohol are of particular interest. The conversion into the esters or chlorides but can also be carried out on the crude or purified reaction product without prior isolation the acid can be carried out by methods known per se. To this end, will the reaction product converted into a powder. Spray drying does the job the aqueous solution of the reaction product, in turn, serves particularly well because the salt is obtained in a particularly reactive form.

The inventive method it has become possible to easy way to get heterocyclic di- or tricarboxylic acids. So one has z. B. Isocinchomeronic acid (pyridine-2,5-dicarboxylic acid) so far by nitric acid oxidation made of 2-methyl-5-ethylpyridine. The dehydro-mucic acid (furan-2,5-dicarboxylic acid), which previously had to be prepared from hexoses by laborious processes is now easy to obtain from pentoses via furfural.

The heterocyclic ones produced by the process according to the invention Di- and tricarboxylic acids can be used wherever di- or Has used tricarboxylic acids, e.g. B. in the production of plasticizers, synthetic resins and as acidic components in the manufacture of polyesters.

Example 1 A mixture of 40 g of potassium nicotinate and 1.2 g of cadmium fluoride was in a rolling autoclave of 0.2 1 Content in the before beginning of the experiment, 50 atm of carbon dioxide had been injected, 2 hours at 370 "C heated. The pressure rose to 140 atm.

The pyridine-containing reaction product became in about 400 cm3 of water dissolved and after filtering off the catalyst and carbonaceous products with Acidified hydrochloric acid. 10.1 g of isocinchomeronic acid crystallized on cooling = 48.801, based on the theory. To The melting point was 2480 when recrystallized from water C, the AN was 669 (calculated 671). To identify the acid she was using Methanol and a little concentrated sulfuric acid boiled under reflux. The received After recrystallization, dimethyl ester had a melting point of 1610 ° C. (163 ° C. according to the literature).

The yield of pyridine obtained according to the reaction equation theoretically, it should have been produced in an amount of 13 g, was not determined quantitatively; however, it was present in nearly the required amount.

Example 2 A mixture of 40 g of potassium nicotinate and 1.2 g of cadmium fluoride was in a roller autoclave with a capacity of 0.2 l, in which 50 atm of carbon dioxide had been pressed in, heated to 420 "C for 11/2 hours. The The pressure rose to 157 atm.

The pyridine-containing reaction product became hot in about 200 cm3 Dissolved water, treated with activated charcoal, filtered and acidified with hydrochloric acid. After cooling to 0 ° C., the isocinchomeronic acid obtained was filtered off with suction and dried. The yield was 10.6 g = 51.00 /, of theory.

Example 3 A mixture of 40 g of potassium picolinate and 1.2 g of cadmium fluoride was in a roller autoclave with a capacity of 0.2 l, in which 50 atm of carbon dioxide had been pressed in, heated to 380 "C for 2 hours. The pressure rose to 155 atm.

The pyridine-containing reaction product became hot in about 200 cm3 Dissolved water, filtered and acidified with hydrochloric acid. After concentration and cooling 9.7 g of isocinchomeronic acid = 46.8 ° lo of theory also crystallized from the solution SZ = 678. The acid was identified via the dimethyl ester.

Example 4 A mixture of 40 g of potassium isonicotinate and 1.2 g Cadmium fluoride was in a roll autoclave of 0.21 capacity, in the before the beginning of the Test 50 atm of carbon dioxide had been injected, heated to 390 "C for 2 hours. The pressure rose to 130 atm.

The reaction product, weighing 32.4 g, was dissolved in 200 cm3 of hot water dissolved, filtered and acidified with hydrochloric acid. On cooling, 5.2 crystallized g = 25% of the theory isocinchomeronic acid, which is identified via the dimethyl ester became. After some time, 5.3 g of the monopotassium salt also separated from the mother liquor the pyridine-2,4,6-tricarboxylic acid, which was identified by the triethyl ester.

Example 5 44 g of quinolinic acid were added to a roll autoclave with a capacity of 0.21 Potassium, which had been dried over phosphorus pentoxide at 150 ° C. in vacuo, after Pressing in 50 atm of carbon dioxide without the addition of a catalyst for 3 hours 3900 C heated. The final pressure was 150 atm.

The crude product, weighing 35.5 g, was placed in about 200 cm3 of hot water dissolved, treated with activated charcoal, filtered and then acidified with hydrochloric acid. At the Cooling crystallized out 14.75 g = 48.80 / o of theory isocinchomeronic acid.

Example 6 A mixture was placed in a roll autoclave of 0.21 capacity from 55 g of the dipotassium salt of quinolinic acid (dried as in the previous example) and 2 g of cadmium fluoride after injecting 50 atm of carbon dioxide for 3 hours 390 "C, with a maximum pressure of 127 atm.

The gray crude product, weighing 50 g, was dissolved in 300 cm8 of hot water dissolved, filtered and acidified with hydrochloric acid. 16.0 crystallized on cooling g = 42.3% of the theory of isocinchomeronic acid. Separated after concentrating the filtrate In addition, 7.6 g of the monopotassium salt of pyridine-2,4,6-tricarboxylic acid are obtained.

Example 7 40 g of potassium nicotinate were in one without a catalyst Roll autoclave with a capacity of 0.21, in which 50 atm of carbon dioxide were added before the start of the experiment had been pressed in, heated to 400 ° C. for 3 hours. The pressure rose in the process 150 atm.

The crude product, which weighed 23.1 g, was worked up in the manner described and resulted in 6.4 g of isocinchomeronic acid = 370 / of theory.

Example 8 40 g of potassium nicotinate were in one without a catalyst Rolling autoclave with a capacity of 0.2 l, into which 50 atm of carbon dioxide were added before the start of the experiment had been pressed in, heated to 390 "C for 3 hours. The pressure rose in the process 125 atm.

The crude product, which weighed 26.4 g, was worked up in the manner described and gave 8.0 g of isocinchomeronic acid = 38.70 /, of theory.

Example 9 In a roller autoclave with a capacity of 0.21, an intimate Mixture of 62.4 g of potassium pyromuconate (furan-2-carboxylic acid potassium) and 3.3 g (501, Cadmium fluoride is filled in and after the air has been displaced by carbon dioxide Initial pressure of 50 atm of this gas forced on. The autoclave was then 2 hours rolled at 3200 C. A maximum pressure of 200 was established during the heating process atm, which almost fell back to the starting amount after cooling. The raw product weighed 50.6 g and, after pulverization, was suspended in 0.5 l of water and boiled. After the formed charcoal and the catalyst had been filtered off, became the clear filtrate was adjusted to a pH of 3.5 with hydrochloric acid. At this optimum precipitation the dehydro-mucic acid (furan-2,5-dicarboxylic acid) almost completely precipitates, while small amounts of unreacted pyrocucous acid only after further acidification this filtrate crystallize out. The dehydro-mucic acid obtained in this way (16.5 g) is 98% after drying, corresponding to an acid number of 700.

The dehydro mucic acid was characterized by the following derivatives: AN of the acid purified via the dimethyl ester = 712; Dimethyl ester: Kr.15 = 155 ° C, F. = 111 "C, VZ = 609.2; dichloride: Kr.12 = 122" C, F. = 79 to 80 "C.

Example 10 Under the same other conditions as in Example 9 were 50.0 g of potassium pyromuconate with 50 atm of nitrogen in a roller autoclave for 1 hour Treated at 330 "C.

The crude product, weighing 43.4 g, was obtained after appropriate work-up 8.3 g of crude dehydro-mucic acid.

Example 11 In a roll autoclave with a capacity of 0.2 l was a mixture filled in from 46.0 g of the potassium salt of thiophene-2-carboxylic acid and 2.3 g (50 / o) of cadmium oxide. The air in the autoclave was displaced by carbon dioxide.

Then 50 atm of this gas were injected.

The batch was then heated to 340 ° C. for 1 hour.

After the reaction, the powdered reaction product became almost colorless suspended in 0.5 l of water and the filtrate made Congo acidic with hydrochloric acid. the precipitated dicarboxylic acid, which is very sparingly soluble in water, was treated with warm water digested and was obtained in an amount of 14.9 g. When thiophene-2,5-dicarboxylic acid was used they are characterized by the following derivatives: Dimethyl ester: F. = 147.5 ° C, Kr.14 = 176 ° C; Diethyl ester: F. = 50 ° C.

Example 12 A 1.5-1 rotary autoclave was filled with a mixture of 300 g of potassium pyromuconate and 30 g of anhydrous cadmium chloride were charged. At room temperature 50 atm of carbon dioxide were injected. During the heating to 330 "C, the Pressure to 180 atm and dropped to 330 "C and then after heating for 2 hours Cools back almost to the initial value. The reaction product weighed 284 g and was Worked up analogously to Example 9. The yield of dehydro-mucic acid was 106 g.

Example 13 In a stationary autoclave, one with glass wool Thick-walled test tube with a capacity of 15 ml wrapped and clogged with glass wool used, which with an intimate mixture of 3 g of potassium salt dried at 140 ° C the pyrrole-2-carboxylic acid and 0.3 g of cadmium fluoride was filled. In the then locked 50 atm of carbon dioxide were injected into the autoclave. Then 1 hour at 3000 C heated.

After cooling down and relaxing, it was hardly discolored, powdery Reaction product, which weighed 2.8 g, dissolved in 70 ml of hot water and removed from the cadmium fluoride filtered off. The pH was then adjusted to 2 with hydrochloric acid and the precipitating, very pure pyrol-2,5-dicarboxylic acid immediately filtered off. After drying lay 1.26 g of dicarboxylic acid.

The filtrate separates further dicarboxylic acid when standing for a long time, but with dark colored condensate sation products is contaminated. The pure Acid can be obtained from it via the ester.

Example 14 A mixture of 20 parts of the dipotassium salt of pyrazinedicarboxylic acid (2,3) and 1 part of anhydrous cadmium chloride was in a roller autoclave with 50 atm of carbon dioxide initial pressure Rolled at 330 "C for 1 hour.

After releasing the pressure from the autoclave, the dark brown reaction product became suspended in 300 parts of water, the catalyst and by-products are filtered off. Boiling with activated charcoal will make the brownish filtrate completely colorless. By acidification of the filtrate on a PEX = 1, 4 parts of pyrazinedicarboxylic acid (2.5) crystallized off, weighed as anhydrous acid, corresponding to 300 / o of theory.

Example 15 7.6 parts of the potassium salt of pyrrole-a-carboxylic acid mixed with 100% cadmium fluoride and placed in a roller autoclave after setting 50 atm Carbon dioxide initial pressure heated at 290 ° C for 1 hour. According to an example 13 corresponding Working up, 0.9 parts of pure pyrrole-a, a'-dicarboxylic acid were obtained.

Example 16 As in Example 9, 50 g of sodium pyromuconate were obtained in a mixture with 50% cadmium fluoride for 1 hour at 330 "C with an initial pressure of 50 atm. carbon dioxide heated.

The crude reaction product, which weighed 48.5 g, was converted into 4.6 g of crude dehydroglucic acid obtain.

Example 17 30 g of quinaldinic acid were placed in a roller autoclave with a capacity of 0.21 Potassium (anhydrous) heated to 360 "C for 2 hours with 1 g of cadmium fluoride. With a Temperature, from 1500 C 50 atm of carbon dioxide were injected; the final pressure at 3600 C was 70 atm.

The reaction product was washed out with ether to remove the resulting To remove quinoline, then it was dissolved in hot water with activated charcoal treated and filtered. After acidification with hydrochloric acid, 3.4 g crystallized = 220 / o of the quinoline-2,4-dicarboxylic acid theory. After concentrating the mother liquor a further 2.2 g of a mixture of quinoline mono- and dicarboxylic acids were obtained.

Example 18 30 g of nicotinic acid were added to a roll autoclave with a capacity of 0.21 Sodium heated to 400 ° C. for 3 hours without a catalyst. At the beginning of the experiment, 50 atmospheres of carbon dioxide imposed. The final pressure at 4000 C was 150 atm. The 23.1 The reaction product, weighing g, was dissolved in about 250 cm3 of water, filtered and mixed with Acidified hydrochloric acid. After concentrating and cooling the solution, 6.4 crystallized g = 370 / o of the theory of isocinchomeronic acid.

Claims (1)

PATENT CLAIMS: 1. Process for the preparation of heterocyclic Dicarboxylic acids or mixtures of heterocyclic di- and tricarboxylic acids or optionally of derivatives of these acids, characterized in that alkali salts are used of carboxylic acids, their carboxyl groups on heterocyclic ring systems of aromatic Character stand, preferably under the pressure of an inert gas, at temperatures between 275 and 5000 C heated and optionally the salts obtained in per se known Manner converted into the free acids or into derivatives of the same 2. Process according to Claim 1, characterized in that the salts are heated to temperatures of 330 to 4500 C heated. 3. The method according to claim 1 and 2, characterized in that one in the presence of the metals Zinc, cadmium, mercury, lead or their compounds works Considered publications: Gattermann-Wieland, Die Praxis des Organic Chemist, 32nd Edition, p. 329 (1947); Ber. L German chem. Ges., BL 21, pp. 1077-1078 (1888); Monh f. Ch, Vol. 10, pp. 375 to 377 (1889).