The way to obtain the calcium salt of phenylpyruvic acid

 

(57) Abstract:

The inventive product is pyruvic acid. B. F. C18H14O6Ca. Output 70-75% impurity Content of 5-6% Reagent 1: benzylchloride. Reagent 2: monoxide. Reaction conditions in aqueous-alcoholic medium at 35-45°C and a pressure of 1-5 atmospheres in the presence of oxide or calcium hydroxide and catalyst-carbonyl compounds of cobalt in the cobalt concentration of 1.5-4.0% 1 table.

The invention relates to organic chemistry, in particular to methods of producing the calcium salt of phenylpyruvic acid.

Phenylpyruvic acid (FPC) and its salts is used for phenylaniline, which is used in the pharmaceutical industry and as a major component of the low-calorie sweetener aspartame.

A method of obtaining phenylpyruvic acid carbonyliron benzylchloride the carbon monoxide in the presence of carbonyl complexes of cobalt and inorganic bases on the basis of alkali-earth metals in the environment water-soluble solvent of dioxane in the presence of water at a pressure of carbon monoxide 5-60 and at a temperature of 50-90about[1]

Despite the fairly high output is the same dioxane is prone to the formation of peroxides, that informs the production of the explosive.

A method of obtaining the FPC carbonyliron benzylchloride on the cobalt carbonyl in the presence of calcium hydroxide in the environment of the water-soluble solvent acetonitrile at a pressure of 2-100 at. the temperature of 50-100aboutC. Output FPC 60-70% [2]

The advantage of this method is the possibility to obtain the target product at low pressure (3.3 ATA), however, the FPC output low 62% at a temperature of 75aboutSince, moreover, in the method using solvent inaccessible.

Also known is a method of obtaining the FPC carbonyliron benzylchloride on the cobalt carbonyl in the presence of calcium hydroxide at a temperature of 20-150aboutC and the pressure of carbon monoxide 1-140 at. [3] the Reaction is carried out in a two-phase system consisting of water and ketone, slightly soluble in water (isobutyl ketone, acetophenone). Output FPC 70-82% Under pressure of carbon monoxide of 2 at. and temperature 55aboutWith the release of FPC 72.1% of phenylacetic acid and 17.9%

However, the process in the two-phase system is technologically difficult process, although in mild conditions (low enough temperature for the carbonylation 55aboutWith the low pressure of 20 bars) obtained target products with acceptable vihibala closest to the technical nature of the invention is a method for phenylpyruvic acid carbonyliron benzylchloride in the presence of bases, alkaline earth metals calcium, barium, strontium using catalysts on the basis of the CARBONYLS of cobalt, iron, Nickel in spirit aqueous environment (isopropyl, tributyl alcohols) (4-prototype).

The process is performed at a pressure of 5-200 at. (mostly 20 to 100 ATM) and a temperature of 40-100aboutWith (mostly 50-70aboutC). Receive insoluble (calcium, barium, strontium salt FPC, which is transferred to the FPC by the oxidation of hydrochloric acid and was isolated by extraction with ether. In the liquid phase remains phenylacetic acid (FOOK) in the form of a soluble calcium salt, which, after acidification of the filtrate are extracted with ether. Output FPC 70-80%

In the method using the available solvents (isopropyl, tributyl alcohols), but for best results, the process is carried out in harsh conditions: the output of the FPC (70-80%) is achieved at a pressure of 30-50 ATM and a temperature of 50-60aboutSince, moreover, when carrying out the process at a pressure below 5 at. the output of the FPC is less than 20% of small selectivity of the process, because produces 10-20% of impurities. Because of these defects, the process is energy intensive and not very effective.

The technical result of the invention is to increase the selectivity of the formation of calcium Saleem high yield of the target product.

The technical result is achieved by a process for the carbonylation of benzylchloride in aqueous-alcoholic medium with the use of oxide or calcium hydroxide and catalyst carbonyl compounds of cobalt in the cobalt concentration of 1.5-4.0% per benzylchloride at a pressure of 1-5 atmospheres and a temperature of 35-45aboutWith, followed by separation by filtration of the target product.

A distinctive feature of the method is to conduct the process at a pressure of 1-5 atmospheres. and a temperature of 35-45aboutC.

The implementation of the invention provides an output of the calcium salt of the FPC 70-75% and reduced formation of impurities up to 5-6%

In the carbonylation under mild conditions (combination of low temperature and low pressure catalytic complex obtained thermodynamic stability and the reaction takes place mainly in the direction of formation of the calcium salt of the FPC, which provides the output of the target product 70-75% and reduced formation of impurities up to 5-6%

The present method can be carried out in the ordinary equipment designed for low pressure, which makes the process much more well-known.

The efficiency of this process can be increased due to the use in the manufacture of medicinal products, as well as fragrances and dyes.

These benefits not only simplify the process but also reduce energy costs by carrying out the process at low temperature and pressure.

The invention provides a method of obtaining calcium salt of the FPC by carbonylation of benzylchloride in the reaction flask or autoclave, which is pre-rinsed with nitrogen and carbon monoxide.

The solvent used is known alcohols: isopropyl (IPA), tributyl (TBS) and other

When choosing the reaction conditions necessary to observe the correspondence between pressure and process temperature. Conducting the reaction at low pressure and temperature allows to obtain the highest yield of the target product and the lowest output of impurities. When the temperature rises above stated, and low pressure catalytic stability of the complex decreases, which decreases the yield of the target product. If the temperature and pressure to increase to 60aboutAnd 6 ATM, it decreases the yield of the target product and increases the amount of impurities.

Carbonylation is carried out at intensive stirring and continuous supply of carbon dioxide to obrazovavshikhsya products in the form of acids. For separation of the target product, the reaction mixture is filtered in a stream of nitrogen and calcium salt FPC remains on the filter. The content of the target product in the sediment is determined by GLC. From the filtrate the solvent is distilled off and expose his or acid (hydrochloric acid) or alkaline (a mixture of hydroxide and sodium carbonate or calcium) hydrolysis followed by separation FOOK in the form of crystals or sodium or calcium salt, depending on the needs.

The possibility of implementation of the method is confirmed by examples. Conditions for carbonylation and the results are shown in the table. Numbers 8 and 9 show the data from the prototype for comparison. The data given in the table.

P R I m e R 1. In temperature-controlled flask is charged with: Isopropyl alcohol 50 ml Water, 6 ml of Benzyl chloride (4.4 g 34,75 10-3mol calcium Oxide 3.4 g 60,7 10-3-"- Cobalt carbonyl 0.32g 0,94 10-3-"- including metal. cobalt 0.11 g 2 10-3mol

The concentration of cobalt in the calculation of benzylchloride is 2.5%

The process is carried out at 37aboutC, atmospheric pressure of carbon monoxide in air for 7 h until complete consumption of benzylchloride. After the selected reaction medium, the sample, and the filter, washed with isopropyl alcohol and water, and dried. In the sediment (6.5 g) receive calcium salt FPC (the content of 70.8%) with a mixture of oxide and hydroxide of calcium.

From the filtrate evaporated excess of IRS in the form of an azeotrope with water, to the residue add an aqueous solution of a mixture of hydroxide and sodium carbonate (1:1) in stekhiometricheskom number to FOOK (sodium 0.25 g) and heated 2 hours When this is the reaction of the alkaline hydrolysis of isopropyl ether FOOK and the exchange reaction of calcium to sodium in the calcium salt of the FPC. The resulting salt FOOK remains in aqueous solution in the amount 1,32, It can be used in aqueous solution or dry for easy transportation.

P R I m m e R 2. The method is carried out analogously to example 1, but with the difference that the pressure is increased to 3 ATM. This increases the output of the FPC and the speed of the process in order to preserve the total yield of target products.

P R I m e R 3. The method is carried out analogously to example 1, but with the difference that the temperature of the carbonylation 35, a pressure of 5 ATM, and the cobalt concentration of 2.0% With the FPC 71% decreased the formation of impurities due to temperature reduction.

P R I m e R 4. The method is carried out analogously to example 1 with the difference that the temperature of the 40aboutWith speed and by reducing the concentration of the catalyst.

P R I m e R 5. The method is carried out analogously to example 2 with the difference that the temperature 45aboutC. it increases the output of the FPC to 74% and accelerated reaction (5 h).

P R I m e R 6. The method is carried out analogously to example 1 with the difference that the temperature of the 35aboutAnd the cobalt concentration of 4% With the FPC increases with the simultaneous reduction of impurities and accelerate the process.

P R I m e R 7. The method is carried out analogously to example 1 with the difference that as alcohol use tributyl alcohol. When the FPC increases, but increases the amount of impurities and the process is slower.

The WAY to OBTAIN the CALCIUM SALT of PHENYLPYRUVIC ACID carbonyliron benzylchloride in aqueous-alcoholic medium at elevated temperature and pressure with the use of oxide or calcium hydroxide in the presence of a catalyst carbonyl compounds of cobalt in the cobalt concentration of 1.5 to 4.0% per benzylchloride, followed by separation by filtration of the target product, wherein the carbonylation is carried out at a temperature of 35 to 45oC and the pressure of carbon monoxide of 1 to 5 ATM.

 

Same patents:

The invention relates to the field of fine organic synthesis, particularly to a method of obtaining p-butylbenzoic acid

FIELD: chemistry.

SUBSTANCE: method involves impulse evaporation of flow discharged from reactor to form upper distillate; further treatment of upper distillate by distillation in standard operational conditions, obtaining acetic acid; running control of acetic acid formation rate by regulation of at least one independent process parametre; running control of acetic acid formation rate by regulation of at least one dependent process parametre; acetic acid formation rate reduction in response to changes in the process course of process equipment state; process control at reduced acetic acid formation rate by regulation of at least one of independent and/or dependent parametre during return of process equipment system to original state of standard operational process before the said change; increase of acetic acid formation rate until the system returns to original state of standard operational process by regulation of at least one of independent and/or dependent parametre, where non-linear multivariant regulation is based on the process model.

EFFECT: improved cost efficiency.

3 cl, 2 ex, 3 dwg

FIELD: chemistry.

SUBSTANCE: method involves the following steps: (a) separation of a carbonylation product to obtain a gaseous overhead fraction containing acetic acid, methanol, methyl iodide, water, methyl acetate and at least one permanganate reducing compound, including acetaldehyde and less volatile fractions of catalyst; (b) distillation of the gaseous overhead fraction to obtain purified acetic acid and a low-boiling gaseous overhead fraction containing methanol, methyl iodide, water, acetic acid, methyl acetate and at least one permanganate reducing compound, including acetaldehyde; (c) condensation of the low-boiling gaseous overhead fraction and its separation into a condensed heavy liquid fraction which contains methyl iodide and methyl acetate and a condensed light liquid fraction containing water, acetic acid and at least one permanganate reducing compound, including acetaldehyde; (d) distillation of the light liquid fraction in a separate distillation column to obtain a second gaseous overhead fraction containing methyl iodide and at least one permanganate reducing compound, including acetaldehyde, and residue containing a fraction of high-boiling liquid containing methyl acetate, water and acetic acid, where the second gaseous overhead fraction is rich in permanganate reducing compounds relative the light liquid fraction; (e) condensation of the second gaseous overhead fraction containing methyl iodide and at least one permanganate reducing compound, including acetaldehyde, and aqueous extraction of the condensed stream to obtain a stream of an aqueous solution containing permanganate reducing compounds, including acetaldehyde, and a raffinate containing methyl iodide.

EFFECT: selective extraction and reduced amount of permanganate reducing compounds.

20 cl, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing oxalic acid, involving feeding carbon dioxide through 1.0-13.0 M aqueous trifluoroacetic acid solution which is saturated with oxygen at temperature of 15-25°C and atmospheric pressure. Oxalic acid is separated by evaporating the obtained product. The invention can be used in chemical industry.

EFFECT: method which enables to produce oxalic acid in a single step at room temperature and atmospheric pressure.

2 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to processes of recycling of hydrocarbon gases with obtaining liquid chemical products, in particular to obtaining glycolic acid ethers. method of obtaining methyl ether of glycolic acid includes stages of formaldehyde carbonylation and glycolic acid etherification, where ethane or ethane-containing hydrocarbon gas is mixed with oxygen or oxygen-containing gas in molar ratio ethane:oxygen, equal to 40÷1:1, oxidation at temperature 350-550°C and pressure 20-40 bar, cooling of obtained products and their separation into flow (I), containing formaldehyde and water, and flow (II), containing CO, methyl and ethyl alcohols, and ethane and methane that did not react, supply of flow (I) to the stage of formaldehyde carbonylation with obtained in the process CO, supply of flow (II) to the stage of glycolic acid etherification with contained in flow composition methyl and ethyl alcohols, after the stage obtained are: flow of etherification products (III), from which methyl ether of glycolic acid is separated by known methods, and flow (IV), containing CO, ethane and methane that did not react, flow (IV) is supplied to the stage of carbonylation, ethane and methane that did not react, after the stage of carbonylation are partly returned to partial oxidation and/or are used as fuel gas.

EFFECT: considerable simplification of technology in comparison with known methods of obtaining glycolic acid ethers, elimination of highly energy-consuming and capital-intensive stage of synthesis-gas obtaining.

4 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: synthesis method by 13C-linoleic, 13C-linolenic, 14C-linoleic and 14C-linolenic acids includes the carbon dioxide condensation, marked by 14C or 13C, with the Grignard reagent, produced from 1-bromo-8.11-heptadecandiene (in case of linoleic acid) or from 1-bromo-8.11.14-heptadecanthriene (in the case of linolenic acid), carried out in the following sequence of steps: a - production of the Grignard reagent by the reaction of metallic magnesium with 1-bromo-8.11-heptadecandiene (in case of linoleic acid) or with 1-bromo-8.11.14-heptadecantriene (in case of linolenic acid) in the presence of metallic iodine; b - carboxylation of the Grignard reagent, produced at point a, for 5-15 min at temperature -20°C at constant stirring, carbon dioxide, marked by 14C or 13C, produced by the sulfuric acid of barium carbonate decomposition, marked by 14C and 13C, at the CO2 pressure of not more than 500 mm Hg. (maintaining by the drop metering of sulfuric acid); after stopping the pressure change in the system, the reaction flask is cooled with the liquid nitrogen in order to provide the quantitative transfer of the remaining in the system 14CO2 or 13CO2 in it, close the tap connecting the device to the CO2 source, and the reaction mixture is stirred for 15 minutes at the temperature -20°C with the purpose to fully incorporate the isotopically marked carbon dioxide into the product of the synthesis: linoleic or linolenic acid.

EFFECT: target products manufacture process acceleration, reduction of carbon dioxide losses, increase of its total chemical and radiation yield in comparison with the prototype, and elimination of the isotope-marked atoms distribution along the entire length of the acyl chain, the simplification and cheapening of the target products the linoleic and linolenic acids manufacture process, is ensured by the decrease in the duration, the increase of the radiation and chemical yield of the product along the source of the isotope in comparison with the prototype, the radioactive wastes release into the external environment is almost completely excluded, as its inclusion into the target product is approaching to the quantitative.

10 tbl, 2 ex, 4 dwg

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using compounds of (R,S)-2-arylpropionic acids of the formula (Ia) , and their (R)- and (S)-isomers as inhibitors of neutrophile (PMN leukocytes) chemotaxis induced by IL-8. These compounds elicit unexpected ability to inhibit effectively IL-8-induced chemotaxis and degranulation of neutrophiles being without significant effect on activity of cyclooxygenases. These compounds can be used in treatment of such diseases as psoriasis, ulcerated colitis, melanoma, chronic obstructive pulmonary disease, bulla pemphigus, rheumatic arthritis, idiopathic fibrosis, glomerulonephritis, and for prophylaxis and treatment of damages induced by ischemia and reperfusion.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

9 cl, 3 tbl, 43 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new method for production of m- or p-substituted α-arylalkanecarboxylic acids of general formula I

from respective α-hydroxylated derivatives using inexpensive reagents and without converting of any reducible groups such as ester or ketone ones in side chains. In formula R is hydrogen, C1-C6-alkyl; R1 is hydrogen, linear or branched C1-C6-alkyl, phenyl, p-nitrophenyl, alkali or earth-alkali cation or cation of pharmaceutically acceptable ammonia salt: A is C1-C4-alkyl, aryl, optionally substituted with one or more alkyl, hydroxy, etc., aryloxy, arylcarbonyl; A is in m- or p-sites; P - linear or branched C1-C6-flkyl, phenyl, nitrophenyl. Claimed method includes the next steps: a) converting of compounds of formula II to compound of formula III either by reaction of II with compound of formula in presence of organic or inorganic base or by reaction of II with thiophene of formula and followed by reaction of obtained product with HNRaRb, wherein Ra andRb are as defined above; b) thermal rearrangement of III to form IIIb ; c) catalytic dehydration of IIIb to form IIIc ; and d) optional hydrolysis of IIIc to obtain target compound of formula I. Also are disclosed new compounds of formulae III and IIIb.

EFFECT: new α-arylalkanecarboxylic acids and intermediates thereof.

6 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.

EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.

2 ex, 7 dwg

Up!