MXPA98004815A - Continuous procedure to produce aqueous solutions of alkaline acid salts arilaceti - Google Patents

Abstract

The invention relates to a continuous process for producing an aqueous solution of an alkali metal salt of an arylacetic acid by alkaline hydrolysis of an arylacetonitrile, this process consisting of contacting, in a mixing zone, an arylacetonitrile with an aqueous solution of an alkali hydroxide. , in introducing the obtained mixture into a reaction zone, in transferring the medium from in a separation zone and then in a distillation zone, and then in recovering the optionally neutralized and diluted aqueous solution of the alkali metal salt of arylacetic acid; It also refers to a plant to perform the procedure

Description

DESCRIPTIVE MEMORY CONTINUOUS PROCEDURE TO PRODUCE AQUEOUS SOLUTIONS OF ALKALINE ACIDS OF ARILACTIC ACIDS The invention relates to a continuous process for producing aqueous solutions of alkaline salts of ar-acetic acids. The alkali salts of arylacetic acids are important starting materials in the chemical industry. They are widely used for the synthesis of various pharmaceutical products. Therefore »in sodium or potassium lacetates are synthetic intermediates for the preparation of penicillin G. Also» these alkaline salts of arylacetic acids can be precursors for the synthesis of arylacetic acids and their esters used in particular for the preparation of pharmaceutical products »Dyes and fragrances. The presently described methods for obtaining alkaline salts of arylacetic acids consist in performing the alkaline hydrolysis of arylacete. This alkaline hydrolysis reaction is a slow reaction that requires efficient agitation means and prolonged heating which, due to the instability to heat the rings, is of a nature to lead to the formation of side products, which decreases the yields and leads to subsequent costly purification operations "that are prohibitive to an industrial process.The raw aqueous alkaline solutions as obtained above" ie the unpurified solutions "may be acidified to produce arylacetic acids which must then be purified by distillation or In order to shorten the induction period of the alkaline hydrolysis reaction, US Pat. No. 2,817,681 recommends using a light weight amount (preferably from 5% to 10% relative to the arylacetonitrile used) of the acid aric lac co ( or its salts) corresponding to the lacetoni r to be hydrolyzed. Then the addition of 5.4 wt.% of 3-methoxy-4-ethoxyphenoacetic acid relative to 3-methoxy-4-ethoxyphene 1 acetoni allows the reaction time to be reduced to about 2 hours. However, it is observed that it is necessary to purify and decolorize the acidified solution and that the relaxation of 3-methoxy-4-ethoxyphene lactic acid only increases from 75% -80% (without minor addition of arylacetic acid during the alkaline hydrolysis reaction). ) to 91% (without addition). It is also known that arylacetic acids can be prepared by direct acid hydrolysis of ary laceton tri. Sulfuric acid is generally used, but its use has many disadvantages. Little selectivity is observed, due to the presence of by-products resulting in particular from the sulfonization of the aromatic rings. Consequently »the relaxations are low and in addition there are effluents such as ammonium sulfate which is difficult to replace without further costly processing. The aqueous solutions of alkali salts of said arylacetic acids - obtained by acid hydrolysis of arylacetons - can be obtained by the neutralization of said arylacetic acids. However, this way of working is expensive since the preparation of said arylacetic acids by acid hydrolysis of ary lacetoni ri is a relatively non-selective and equally expensive operation. The Applicant has found a simple and continuous process that makes it possible, in a very short time, to obtain aqueous solutions of alkali salts of arylacetic acids by alkaline hydrolysis of arylactones, this process does not have all those disadvantages and »in addition» allows pure arylacetic acids are obtained by the simple aci ification of these solutions. Therefore the invention relates to a continuous process for the preparation of an aqueous solution of an alkaline salt of arkacetic acid of the formula: (I) wherein R represents a straight or branched aliphatic hydrocarbon radical having a carbon number ranging from 1 to 10, a halogen atom such as chlorine or bromine, a straight or branched alkoxy group having a number of carbons which varies of the S »or a phenoxy group; M represents an alkali metal such as i \! A or K > n is a number that varies from 0 to 5 and x is a number that varies from 1 to 2 with n + x less than or equal to S »by alkaline hydrolysis of an ary 1 aceton of the formula: R »n and x having the same meanings as in the formula ()» according to the reaction (II) + XMOH - > > (I) + XÍ \ IH3; said process being characterized in that it consists essentially of: a) placing in contact, in a mixing zone, an arylacetonium (II) with an aqueous solution of an alkaline hydroxide MOH in a molar ratio of MOH / (II) by at least equal to and preferably between 1.05x and l.20x »b) introduce the mixture obtained in a) to a reaction zone under a pressure less than or equal to atmospheric pressure» and preferably between 2 absolute bars and 12 absolute bars »and in maintaining said mixture in said reaction zone for a maximum period equal to 60 minutes "and preferably between 5 minutes and 30 minutes" at a temperature of between 100 ° C and lBO ° C "and preferably between 130 ° C and 160 ° CJ ) transferring the media obtained in b) to a separate zone, d) transferring the media obtained in c) to a distillation zone "e) optionally placing the solution obtained in d) in contact with a neutralizing agent that is preferably an arylacetic acid of formula in a mixing zone »and then» f) recover an aqueous solution of alkali aryl acetate which can optionally be diluted with water. In accordance with this invention, the aqueous solution of alkali hydroxide of MOH and ary lacetonium (II) can be preheated to a temperature at least equal to 50 ° C, and preferably at a temperature of between 100 ° C and 130 ° C. ° C. Preferably, identical preheating temperatures will be used for the reagents, but, it will not constitute a part of the invention if preheating temperatures are used for the reagents. In accordance with this invention, the mixing technique used in step a) must be adequate to achieve a deep mixture of the reagents. The contact time between the reagents is at most equal to 10 minutes and preferably varies from 0.01 seconds to 6 minutes. According to this invention, the weight concentration of MOH of the aqueous alkaline hydroxide solutions, LQ can vary on a wide scale. It is at least equal to 10%, and preferably between 20% and 60%. In general, common commercial solutions will be used. According to this invention, the reaction medium obtained in step b), which are in the form of an aqueous alkaline solution consisting of the alkali salt of an arylacetic acid and ammonia formed during the reaction, are introduced between an area separation in which most of the ammonia is removed. In this separation zone, the temperature and the pressure are preferably at most the same as in step b). The ammonia recovered advantageously can be substituted in the form of aqueous solutions. Alkaline aqueous solutions of alkaline salt of lactic acid essentially released from its ammonia is introduced into a distillation zone in which the remaining ammonia is removed. The solution is advantageously distilled with superheated steam »air or an inert gas such as nitrogen. The solution leaving the zone of distillation of step d) is advantageously brought into contact "in a mixing zone" with an amount of an arylacetic acid of the formula which is sufficient to neutralize any amount not consumed of alkaline hydroxide no. This will not constitute a departure from the context of the invention, but an inorganic acid such as HCl or H2O is used as a neutralizing agent. Then an aqueous solution of an alkaline salt of arkacetic acid is recovered which can be diluted to obtain an alkali arylacetate solution having a weight concentration of alkali arylacetate which is suitable for subsequent use to obtain a solution of an alkaline salt. of arylacetic acid that is totally soluble at room temperature. This procedure applies more particularly to the preparation of feni 1 acetates of sodium or potassium of feni laceton tr lo. The invention also relates to a plant for B production of aqueous solutions of alkaline salts of ar-acetic acids. This plant »represented schematically in figure 1» consists of a chamber (1) containing a mixing means »provided with a supply of laceton (2) and a supply of aqueous solution of alkaline hydroxide (3), a pipeline (4) to introduce the mixture into a reactor (5) consisting of at least one vertical cylindrical drainage pipe (T), a pipe (6) to introduce the aqueous solution containing an alkali salt of arylacetic acid and ammonia in a chamber (7) containing gas / liquid separation means, a pipe (8) for introducing the degassed aqueous solution into a distillation column (9), a pipe (IO) for introducing the aqueous solution destined in a chamber (11). ) containing mixing media. Provided with a supply of neutralizing agent (12), a pipe (13) for introduction into a chamber (14) containing mixing means, provided with a supply (15) of water »a pipe (16) for introducing the solution of the alkali salt of arylacetic acid in a storage area (17), and ventilation pipes (18) and (19). According to this invention, the mixing means contained in the chamber (1) can consist of some device that allows the deep contact of the reactants to be obtained. In accordance with this invention, static mixers will be used more particularly. These mixers can consist of one or more different or identical mixing elements. These mixing elements may consist of folded sheets or a network of transverse and interleaved blades. Reagents are introduced (1) by supplies (2) and (3). These reagents can be preheated by means not shown in Figure 1. The mixture that comes out (1) is transferred to the pipe (4) in the reactor (5), preferably towards its lower part. It will not constitute any part of the context of the invention if the tube (s) contains a volumetric packing such as Rasch rings, Pal rings, spheres or ordered packing. The number of tubes can vary in an amplitude or degree.

It is proportional to the desired product of the aqueous solutions of alkaline salt of arylacetic acid. The reactor (5) is accommodated with heating means, not shown in Figure 1, as a high pressure steam or heat transmitter fluid. When steam is used, it will not constitute a part of the context of the invention if this vapor is injected with the reagent mixture into the tube (s). To ensure the initial homogeneous heating of the tubes (T), said tube can be pre-filled with an aqueous solution of alkaline hydroxide or with an aqueous solution of an alkaline salt of arylacetic acid, or alternatively with water. The aqueous solution consisting essentially of ammonia and the alkali salt of arylacetic acid leaving the reactor 5 is transported via a pipe S to a gas / liquid separation zone consisting of a separator (7). ) which can be a large vacuum tank in which the ammonia gas is separated from the aqueous solution in particular by pressure reduction. The ammonia gas is evacuated from said separator by the ventilation pipe (18). The aqueous solution is transferred to the distillation means by a pipe (8). In accordance with this invention, the distillation means can consist in particular of Rasching rings »Pall rings or ordered packing» and on the basis of which a steam stream »air or an inert gas is injected. In the capital of said column »the gases that mainly consist of vapor» air or inert gas and in residual ammonia are extracted by the ventilation pipe (19). At the bottom of said column an alkaline aqueous solution of alkali salt of arylacetic acid salt is released which is transported by a pipe (10) to a first mixing zone (11) preferably consisting of static mixers as mentioned above. These mixers can be identical or different from those used in (1). This mixing zone (11) is supplied with an agent capable of neutralizing any excess alkalinity »by the supply line (12). According to this invention, the arylacetic acid corresponding to the hydrolyzed tri-hydrolyzate will preferably be used as a neutralizing agent The neutralized aqueous solution released (11) is transferred to a second mixing zone (14) via a pipe (13). This mixing zone (14) also preferably consists of static mixers as mentioned above and can be identical or different from those used in (1) and (ll) In accordance with this invention »the aqueous solution of the alkali salt of acid lactic acid is diluted with water in this mixing zone (14), the water being introduced by (15). The aqueous solution thus diluted is transferred to a storage area (17) through the pipe (16). According to a variant of the plant, the mixing means contained in the chamber (1) can be incorporated in the reactor (5). In this case, the mixing means can advantageously be placed in the lower part of said reactor (5) or directly in the pipe (s); these mixing means may consist of mixing elements such as those used in the static mixers as mentioned above. The process according to this invention makes it possible to obtain, with a high alkali salt relaxation of arylacetic acid and a virtually quantitative conversion of the corresponding arginine, pure, WH-S-free aqueous solutions. of alkaline salt of arylacetic acid. The process has the advantage of being made using a simple plant which, in particular, lacks a dynamic type agitation system whose nature causes leaks and is costly in terms of energy. The method according to this invention allows great flexibility. In addition, the ammonia formed can be directly substituted .10 in the form of commercially available ammonia solutions. Aqueous alkaline salt solutions of arylacetic acid can advantageously be precursors of arylacetic acids directly obtainable by acidification. The acids obtained do not require expensive purification means since the starting solutions are pure. The following examples illustrate the invention.

EXAMPLE 1 -. O A tubular reactor is used »formed of a stainless steel tube of 2.3 cm in diameter and 18 cm of lake and packed with Rasching rings leaving a work volume of 36 ml. The tube is surrounded by a cover allowing it to be heated by oil circulation. The reactor filled with 26% aqueous sodium hydroxide solution and placed under a nitrogen pressure of 5 bar is heated to 170 ° C. 0.25 mol / h (29.5 g / h) of fen 1 acetoni tri preheated to 100 ° C and 0.30 mol / h of IMaOH in the form of a 26% aqueous solution (46.1 g / h) also preheated to 100 ° C (20% excess) are then introduced into the reactor maintained at 170 ° C under a controlled pressure of 8 bar. The residence time is 30 minutes. The flow leaving the reactor is recovered in a container at atmospheric pressure. After separating a transitory phase corresponding to the sodium hydroxide initially present in the reactor, an aqueous solution of sodium phenylacetate, whose composition is determined by potentiometric analysis and chromatographic analysis (extraction of the organics with a solvent), is obtained according to a stabilized regime. The duration of the test according to the established regimen is 3 hours. Under these conditions, the conversion of phenylacetate to sodium phenylacetate is only 79.5%.

EXAMPLE 2 A tubular reactor is used, formed of a stainless steel vacuum tube of 2.3 cm in diameter and 39 cm in height having a free volume of 162 ml. The tube is surrounded by a cover allowing it to be heated by oil circulation. The pre-reactor is filled with an aqueous solution of sodium phenylacetate at 44% and placed under a nitrogen pressure of 3 bar. It is heated to 150 ° C. 1.5 mol / h (176 g / h) of fem "lacetoni tri preheated to 100 ° C and 1.6 mol / h of NaOH in the form of a 5% aqueous solution (excess of 6.5.) Are then introduced into a chamber of mixing (with magnetic stirring) connected to the base of the reactor After a residence time in said mixer of 3 minutes, the mixture is introduced into the reactor maintained at 150 ° C under a controlled pressure of 3 bar, the residence is 26 minutes The flow leaving the reactor is recovered in a container at atmospheric pressure After separating a transient phase corresponding to the solution of sodium phenylacetate initially present in the reactor, an aqueous solution of sodium phenyl acetate , whose composition is determined by potentiometric analysis and chromatographic analysis (extraction of organic substances with a solvent), is obtained according to a stabilized regime. It is 5 hours under these conditions, the conversion of faith 'lacetonitri into em fem' 1 sodium acetate is 99.7%.

EXAMPLE 3 The same tubular reactor as in Example 2 is used, but packed in Rasching rings leaving a working volume of 82 ml. The reactor pre-lowered with aqueous solution of 44% sodium phenylacetate and placed under a nitrogen pressure of 5 bar is heated to 150 ° C. 0.745 mol / h (87.4 g / h) of fem "lacetoni trilo pre-heated to 110 ° C and 0.833 mol / h of NaOH in the form of a 25% aqueous solution (133.4 g / h) preheated to 95 ° C (excess 11.8%) are then introduced into the same mixing chamber as in Example 2. After a residence time of said mixer of 5.6 minutes »the mixture is introduced to the reactor maintained at 150 ° C under a controlled pressure of 6 bars The residence time is 26 minutes The flow leaving the reactor is recovered in a container at atmospheric pressure After separating a transient phase corresponding to the sodium phenylacetate solution initially present in the reactor, an aqueous solution of Sodium lacetate, whose composition is determined by potentiometric analysis and chromatographic analysis (extraction of organic compounds with a solvent), is obtained according to a stabilized regime. hoisting is 5 hours.

Under these conditions, the conversion of feni lacetoni tr into sodium phenylacetate is 99.6%.

EXAMPLE 4 A device as shown in Figure 1 is used. 175 mol / h (20.55 kg / h) of feni 1 acetoni ri preheated to 105 ° C and 202 msl / h of NaOH (ie a molar excess of 15.4%) in the form of a 25% aqueous solution (32.33 kg / h) also preheated to 105 ° C are introduced in a static mixer Sulzer (1) made of stainless steel 316T? »with 4.8 c in length and 0.48 cm in diameter consisting of 10 elements of type SMXE DN4 (crossed blades) sold by the Sulzer company. After a residence time in said mixer of approximately 0.05 seconds, the mixture is introduced into a tubular reactor made of 316L stainless steel consisting of 6 tubes, each tube having a height equal to 3 and a diameter equal to 2.5 c. These tubes are pre-treated with an aqueous solution of sodium phenylacetate and are maintained at 150 ° C (external heat with steam at 12 bar) under a pressure of 6 bar. The residence time in the reactor is 8.5 minutes. The flow leaving said reactor is introduced by (6) into a gas / liquid separator (7) consisting of a 12-liter vessel made of 316L stainless steel. The aqueous solution of sodium phenylacetate leaving the separator which has been substantially released from its i.H..3 after reducing the pressure at atmospheric pressure has the following average composition: PhCHS! C05il \ ia: 55.2% NaOH: 2.3% NH ,,: 1.1% H ^ O: 41.4% with a residual amount of feni lacetoni tri lo of less than 25 mg / kg. This solution is then introduced by (8) into a theoretical column of 6 distillation plates (9) consisting of stainless ordered packing. The distillation is carried out at a temperature of 120 ° C with steam at 2 bar. A flow emerges from the capital of the column (19) »this flow consisting essentially of ammonia and water» considering that the sodium phenylacetate solution is completely free of its ammonia (residual content of less than 50 ppm) is extracted at the bottom of the column (9) and is introduced »by (ÍO)» in a static mixer type SMXE (11). In this second static mixer (11) the solution obtained from the distillation column, by (10), and a stream of a sufficient quantity of phenylacetic acid (-3.7 kg / h) at 90 ° C, are introduced simul- taneously, for neutralize excess sodium hydroxide, by (12). The solution coming out of the static mixer (11) is then introduced, by (13), into a static mixer (14) identical to (11) at the same time as a stream of water introduced by (15), to obtain a solution of sodium phenylacetate having a weight concentration of 44% sodium phenylacetate. The duration of the test according to the stabilized regimen is 4 hours. The conversion of phenylacetonitrol is virtually quantitative and the molar relaxation of sodium phenylacetate (relative to the emm "lacetonitri lo) is greater than 99.9% .Figure 1 presents several operating parameters and the conversion rates of phenylacetonium for the example 4, together with Examples 5 »6 and 7 made according to a procedure similar to that used in example 4.

TABLE 1 TABLE 1 (continued) EXAMPLE 8 The same device as in example 4 is u i 1 raised. 172.1 mol / h (20.2 kg / h) of feni lacetonitri preheated to 107 ° C and 186.1 mol / h of KOH (ie a molar excess of 8.1%) in the form of a 40.8% aqueous solution (25.6 kg / h) also preheated to 107 ° C are introduced in a static mixer (1). After a residence time in the mixer of approximately 0.065 seconds, the mixture is introduced into the tubular reactor (5), whose tubes are pre-treated with 40.8% potassium hydroxide solution and maintained at 150 ° C under a pressure of 6 bars. The residence time in the reactor is 10 minutes. After an operation time of 30 min, which ensures the complete removal of the initial potassium hydroxide present in the reactor, an aqueous solution of potassium phenylacetate is obtained according to a stabilized regimen of the gas / liquid separator. ), the average composition of this solution after reducing the pressure of the atmospheric pressure, being the following: PhCH3COzK 69.6% KOH 1.85% H, 0.65% Ha0 27.9% with a residual amount of feni lacetoni tri less than 50 mg / Kg. In a similar manner to Example 4, this solution then goes through a steam distillation in column (9) to obtain an additional content of ammonia of less than 50 mg / kg, and is then introduced into the static mixer (11) with an stream of a sufficient amount of phenylacetic acid (-1.9 kg / h) at 90 ° C to neutralize the excess potassium hydroxide. The solution leaving the static mixer (11) is then introduced into the static mixer (14) at the same time as a stream of water »to obtain an aqueous solution of potassium phenylacetate having a concentration of potassium phenylacetate with 64% in weight. The duration of the test according to the stabilized regimen is 5 hours. The conversion of feni 1 acetoni tri lo is virtually quantitative and the molar relaxation of potassium phenylacetate (relative to the phenetal lace) is greater than 99.9%.

Claims (17)

NOVELTY OF THE INVENTION CLAIMS

1. - Continuous process for the preparation of an aqueous solution of an alkaline salt of arylacetic acid from form wherein R represents a straight or branched aliphatic hydrocarbon radical having a carbon number ranging from 1 to 10 »a halogen atom» a straight or branched alkoxy group having a carbon number ranging from 1 to S > or a phenoxy group; M represents an alkali metal, n is a number that varies from 0 to 5 and x is a number that varies from 1 to 2 with n + x less than or equal to 6 »by alkaline hydrolysis of an ary lacetonitri of the formula: R »n and x having the same meanings as in the formula (I), in accordance with the reaction (II) + xMOH »(I) + XNH3; H ... 0 said process being characterized in that it consists essentially in: a) contacting in a mixing zone an ary lacetonium (II) with an aqueous solution of an alkaline hydroxide MOH in a molar ratio MOH / (II) at least same as x and preferably between 1.05x and l.20x. b) in introducing the mixture obtained in a) into a reaction zone under a pressure greater than or equal to atmospheric pressure and in maintaining said mixture in said reaction zone for a period at most equal to 60 minutes at a temperature of between 100 ° C and 180 ° C > c) transferring the medium obtained in b) to a separation zone; d) transferring the medium obtained in c) to a distillation zone; and e) placing the solution obtained in d) in contact with a neutralizing agent in an mixing zone »and then, f) recovering an aqueous solution of an alkaline salt of arylacetic acid.

2. - Procedure according to the rei indication 1 »further characterized in that the contact time between the reagents in the mixing zone of step a) is at most equal to 10 minutes.

3. Process according to the rei indication 2, further characterized in that the contact time between the reagents and the mixing zone of step a) is between 0.01 seconds and 6 minutes.

4. Method according to any of claims 1 to 3, further characterized in that the mixture obtained in step a) is introduced in a reaction zone - step b) - under a pressure of between 2 absolute bars and 12 absolute bars "and is maintained in said reaction zone for a period of between 5 minutes and 30 minutes at a temperature between 130 ° C and 160 ° C.

5.- Procedure of conformity with any of the 0 rei indications from 1 to 4, further characterized because the molar ratio MOH / (II) is between 1.05x and 1.20x.

6. Process according to one of the rei indications from 1 to 5, further characterized in that the neutralizing agent used in which step e) is an arylacetic acid of formula ?

7. Process according to any of claims 1 to 6, further characterized in that the aqueous solution of an alkaline salt of arylacetic acid, obtained in step e), is diluted with water.

8. Method according to any of claims 1 to 7 »characterized in that n is zero.

9. - Method according to any of claims 1 to 8 »characterized in that x = 1.

10 .. - Method according to any of the claims 1 to 9» characterized in that the alkali metal is sodium or potassium.

11. Aqueous solution of sodium phenylacetate obtained according to any of claims 1 to 10.

12. Aqueous solution of potassium phenylacetate obtained in accordance with any of the claims from 1 to 10.

13. Plant allowing the production of an aqueous solution of an alkali metal salt of arylacetic acid in accordance with any of the above indications of the 12, consisting of a chamber 1 containing mixing means supplied with a supply of arylacetonic acid (2). ) and a supply of aqueous alkaline hydroxide solution (3) »a pipe (4) for introducing the mixture into a reactor (5) consisting of at least one vertical cylindrical drainage pipe (T>> a pipe (6) ) to introduce the aqueous solution containing an alkali salt of arylacetic acid and ammonia in a chamber (7) containing gas / liquid separation means »a pipe (8) to introduce the degassed aqueous solution into a distillation column (9), a pipe (19) for introducing the distilled aqueous solution into a chamber (11) containing mixing means, provided with a supply of neutralizing agent (12) , a pipe (13) for introducing it into a chamber (14) containing mixing means »provided with a supply (15) of water» a pipe (16) for introducing the aqueous solution of the alkaline salt of arylacetic acid in an area of storage (17). and ventilation pipes (18) and (19).

14. Plant according to claim 13 »further characterized in that in the chamber (1)» the mixture is made by a static mixer.

15. Plant according to claim 14 »further characterized in that the static mixer consists of at least one mixing element consisting of folded sheets or a network of interleaved transverse blades.

16. Plant in accordance with claim 13, further characterized in that the distillation column (9) contains a package.

17. Plant according to claim 13, further characterized in that the mixing means contained in the chambers (11) and (14) are static mixers.