PL230932B1 - Method for producing diacyl tartaric acids by continuous method - Google Patents

Description

Description of the invention

The subject of the invention is a process for the preparation and crystallization of diacyltartaric acids. Tartaric acid and its compounds, especially diacyl derivatives, are widely used in organic synthesis and play a very important role in the synthesis of optically active compounds. They are most widely used, including on an industrial scale, for the separation of racemic mixtures of amines, amino acids, alcohols and other basic compounds, and more. They are used as separating or derivatizing agents and in chiral chromatographic materials as chiral or matrix additives [L. Synoradzki, U. Bernaś, P. Ruśkowski, Tartaric acid and its O-acyl derivatives. Part 2. Application of Tartaric Acid and of O-Acyl Tartaric Acids and Anhydrides. Resolution of Racemates, Org. Prep. Proc. Int., 2008, 40, 163-200].

The main method of obtaining diacyltartaric acids is the hydrolysis of the corresponding diacyltartaric anhydrides. Both acids and anhydrides are sparingly soluble in water. Some acids (e.g. dibenzoyl and ditoluoyltartaric KDBW and KDTW) crystallize in the form of monohydrates from the emulsion of the water-immiscible phase, which is easily supercooled and lumpy, others (e.g. dianisooyltartaric KDAW) do not form a liquid phase and hydrates, but immediately from the sediment the anhydride turns into acid sediment which is water-repellent, light, creeping, foaming.

One of the known methods for the hydrolysis of diacyltartaric anhydrides was carried out in acetone with water [N. Huh, C. M. Thompson, Tetrahedron, 51, 5935 (1995)] or in water, most often at boiling point, for 0.5-1 h, with or without the addition of a water-immiscible solvent to facilitate acid release [S. Nakai, H. Sato, T. Fujino, JP Patent 6166683, 1992 (EP Patent 600714, 1993); Chem. Abstr., 121, 108498]. Benzene, toluene, xylene and chlorobenzene were used as a solvent. The products were obtained in the form of a very fine, talaty sediment, difficult to filter, dry and transport. The addition of the solvent facilitated the separation, but the solvents used for this purpose are volatile, flammable, have a strong smell, are harmful and pose an explosion hazard. In addition, the organic solvent can reduce the efficiency of the process and additionally causes problems with waste management.

Mezei et al. [HU22147] hydrolyzed dibenzoyltartaric anhydride to the corresponding acid in dichloromethane, with a small amount of water, under a pressure of 0.15-0.5MPa.

From the technological and environmental point of view, the most desirable is to carry out the hydrolysis of diacyltartaric anhydrides in water at a temperature of about 100 ° C. Water is a cheap and ecological reaction medium, the reaction mixture is free of organic solvents, the final product crystallizes from water. However, a problem with hydrolysis in water is the formation of acids in the form of a water-immiscible liquid monohydrate or a suspension of a water-repellent precipitate. For example, dibenzoyltartaric acid and ditoluoyltartaric acid crystallize as monohydrate from the liquid monohydrate phase, and the smooth operation of the process requires a special technical solution because the liquid monohydrates tend to undercool and crystallize rapidly throughout the mass. Crystalline hydrates tend to adhere when crystallizing from water, mainly to the steel to the stirrer and to the reactor walls.

In addition, the acyl groups are also partially hydrolyzed during the hydrolysis of the anhydride bond, which lowers the product yield due to the formation of easily soluble monoacyltartaric and tartaric acids and the poorly soluble corresponding carboxylic acid which co-crystallizes with the product and contaminates it.

To eliminate the above complications, it is possible to carry out the hydrolysis at a lower temperature (35-57 ° C) in water with the addition of acetone (5-50%) in which, for example, KDBW is dissolved. This method allowed to obtain dibenzoyltartaric acid without by-products, but with low yield (60%) [L. Duhamel, J.-C. Plaquevent, Org. Prep. Proced. Int., 14, 347 (1982)].

The known methods of obtaining diacyltartaric acids in an aqueous medium are carried out batchwise. The reaction system is heterophasic throughout the process - raw materials form a suspension, the product forms an emulsion at 100-60 ° C, and the product forms a suspension at room temperature. After reaching 100% conversion of the anhydride to acid, cooling is required and the temperature is kept safe for the product within a specified time. In such circumstances, it is very difficult to carry out the process continuously because a condition for a continuous process is to maintain a uniform stream of suspension and emulsion. On the other hand, the ability to run the process continuously is desirable on an industrial scale.

PL 230 932 B1

The aim of the invention was to develop a continuous method for the preparation of diacyltartaric acids.

The method of obtaining diacyltartaric acids by hydrolysis of the corresponding diacyltartaric anhydrides in water and crystallization from water according to the invention is characterized in that the process is carried out continuously so that diacyltartaric anhydride in water is introduced into the hydrolysis reactor at a hydrolysis temperature of 80-100 ° C, the water / anhydride mass ratio is 0.8-3, and hydrolysis is carried out at 80-100 ° C for 2-25 minutes, then the post-reaction mixture in the form of an emulsion of liquid diacyltartaric acid monohydrate in water is fed to the reactor pre-cooling in which the mixture is cooled to 65-85 ° C while being an emulsion in water, and then the emulsion is fed to a crystallizer where the crystallization step is carried out at 10-55 ° C for 5-20 minutes. Intensive agitation is ensured in the reactors throughout the process so that no sedimentation or phase separation occurs, assisted by the flow of streams between the reactors, which is preferably forced by dosing.

Preferably, the process is carried out in a cascade of 2-5 hydrolysis reactors, in each of which the process is carried out at a temperature of 80-100 ° C, for 2-25 minutes. Preferably, the total time of the hydrolysis step is from 10 to 60 minutes.

Preferably, when starting the process, the reaction mixture fed to the crystallizer is seeded with crystals of the corresponding diacyltartaric anhydride, preferably in an amount corresponding to the concentration of the product suspension at steady state.

Preferred crystallization of the product is carried out at a temperature of 15 to 25 ° C, with a water: KDBW ratio = 3 to 6;

The process according to the invention allows the hydrolysis of diacyltartaric anhydrides and the crystallization of diacyltartaric acids in water in a continuous manner, thanks to the following process conditions:

- in the hydrolysis stage, the reaction mixture is introduced and kept in the reactor for a short time at a high temperature. These conditions are sufficient for hydrolysis to occur, but the time is too short for adverse subsequent reactions to occur;

when the reaction is completed, there is a rapid initial cooling to a temperature at which post-reactions no longer take place;

- intensive mixing and the flow of reagents ensure the maintenance of both the suspension and the emulsion.

The residence time at the appropriate controlled reaction temperature depends on the forced flow rate and is easily determined and modified by the flow control provided by the pump dosing the uniform suspension of raw materials.

The ability to quickly reduce the temperature of the reaction mixture with an appropriate degree of conversion allows practically the elimination of subsequent reactions and achieving conversion to acid and the process efficiency close to 100%. Feeding the crystallizer with a stream of pre-cooled emulsion allows for proper cooling of the stream and rapid crystallization in the crystallizer with product hardening. The separation of the cooling operation into two stages facilitates the technical solution of heat removal. Due to the very high efficiency of the process from the apparatus unit, glass reactors can be used in the process, which is particularly important in the case of a crystallizer, because diacyltartarate hydrates adhere to steel during crystallization and stick to the stirrer and to the walls of the crystallizer. Additionally, the process is easy to start, all the flow reactors are initially filled with water and the stationary state is reached after about 0.5 h from the commencement of dosing of raw materials. An ongoing process can also be easily stopped (e.g. over the weekend) and restarted. The apparatus is washed in a flow of water at the anhydride hydrolysis temperature (80-100 ° C).

In the continuous method of the invention, intensive agitation and forced flow of the reagents keep the substrates suspended and the product emulsified in water and, after crystallization, the product suspended. In addition, the hydrolysis of the anhydride is faster, which makes it possible to carry it out in a shorter time or at a lower temperature, safe for the product. A feed emulsion of hydrates feeds the crystallization process continuously, so it is not necessary to wait for one portion to crystallize before the next portion can be administered. The product in the form of diacyltartaric acid monohydrate crystallizes from the water / KDAcW system already at a ratio of 2: 1, while a 6: 1 ratio was required in the batch process. KDAcW-H2O (hydrate) is well filtered, thanks to which water consumption per 1 kg of the product was reduced threefold. The pure product is obtained with a yield of 97-99%.

PL 230 932 B1

Thanks to the method according to the invention, it was possible to use small reactors with simultaneous achievement of high production capacity. The process is well suited for upscaling and is economical.

The method according to the invention is illustrated in the examples. An exemplary process was carried out in the apparatus shown in the figure, with a variable number of hydrolysis reactors.

Example 1. Preparation of dibenzoyltartaric acid.

In the M mixer with a capacity of At 6 L, 5800 g of dibenzoyltartaric anhydride and demineralized water were suspended in the ratio of water: BDBW = 3 or 2 or 1, respectively, and agitation was started at 700 rpm. Cascade flow-through reactors: R1-Rn hydrolysis, Rc cooling and K crystallizer (250 mL each with agitators) were filled with 250 mL of demineralized water, water flow was started in reflux condensers over R1i-Rn and Rc reactors and 700 mixers were started rpm, regulation and recording of temperature. After reaching the temperature of 90, 92, 95 or 97 ° C in the R1-R3 reactors, the dosing of the BDBW suspension in water was started using a peristaltic pump P, which in the flow range 10-50 mL / min. at the ratio of water: BDBW = 3.2, 1 g / g provided a uniform stream of suspension. The mixture after hydrolysis in the hydrolysis reactors, pre-cooled in the Rc reactor to 65 ° C, drained into the K crystallizer, cooled with water to the temperature of 15-25 ° C, with KDBW-LLO seedlings in the amount ensuring the product concentration in the steady state (from 80 to 125 g / 250 mL of water in the crystallizer). The KDBW-LLO suspension in water flowed from the K crystallizer through the overflow to a flask with a capacity of 6 L. The process was carried out for approx. 3 hours (until the raw material in the mixer was exhausted). At the end of the process, the product was filtered off and dried. A product was obtained in accordance with TWT (Tab. 1)

T a b e l a 1

Example Flow raw materials Water/ BDBW Number of hydrolysis reactors Temperature Σ residence time = hydrolysis time Stream KDBWxH2O Performance (mL / min.) (° C) (min.) (kg / h) (%) 1 50 3 2 97 10 0.88 98.5 2 50 2 3 93 15 1.22 99 3 50 1 5 90 25 1.94 98.5 4 40 3 2 95 13 0.70 98.7 5 40 2 3 92 19 0.97 99 6 40 1 2 97 13 1.55 99 7 10 3 1 97 17 0.24 98.5

Example 2. Preparation of ditoluoyltartaric acid.

In the M mixer with a capacity of At 6 L, 5800 g of ditoluoyltartaric anhydride (BDTW) and demineralized water were suspended in the ratio water: BDBW = 3 or 2, respectively, and agitation was started at 700 rpm. Cascade flow reactors: R1-Rn hydrolysis, Rc cooling and a crystallizer (250 ml each with agitators), were filled with 250 ml of demineralized water, the flow of water in reflux condensers over the R1-Rn and Rc reactors was started, and 700 rpm mixers were started / min., temperature regulation and recording. After reaching the temperature of 95 or 97 ° C in the R1-Rn reactors, the dosing of the BDTW suspension in water was started using a peristaltic pump, which in the flow range 40-50 mL / min. at the water: BDBW ratio = 3 or 2 g / g it provided a uniform stream of suspension After hydrolysis in the hydrolysis reactors, the mixture, pre-cooled in the Rc reactor to 85 ° C, flowed into the K crystallizer, cooled with water to 50-55 ° C, with seedlings KDTW-LLO (the amount of inoculation corresponds to the product concentration in the steady state 60 to 80 g / 250 mL of water in the crystallizer). The KDTW-LLO suspension in water flowed from the K crystallizer through the overflow to the flask with a capacity of 6 L. The process was carried out for approx. 3 hours (until the raw material was used up in the M mixer). At the end of the process, the product was filtered off and dried. A product was obtained in accordance with TWT (Tab. 2).

PL 230 932 B1

T a b e l a 2

Example Flow raw materials Water/ BDTW Number of hydrolysis reactors Temperature Σ time spent. = hydrolysis time Stream KDTWxH2O Performance (mL / min.) (° C) (min.) (kg / h) (%) 8 50 3 2 97 10 0.87 97.5 9 50 2 3 95 15 1.21 98 10 40 2 2 95 10 0.97 97.5

Patent claims

Claims (5)

Patent claims Method for obtaining diacyltartaric acids by hydrolysis of the corresponding diacyltartaric anhydrides in water and crystallization from water, characterized in that the process is carried out continuously so that a stream of diacyltartaric anhydride in water is introduced into the hydrolysis reactor at a hydrolysis temperature of 80-100 ° C, the water / anhydride mass ratio is 0.8-3, and hydrolysis is carried out at 80-100 ° C for 2-25 minutes, then the post-reaction mixture in the form of an emulsion of liquid diacyltartaric acid monohydrate in water is added to a pre-cooling reactor where the mixture is cooled to 65-85 ° C while maintaining the form of an emulsion in water, and then the emulsion is fed to the crystallizer, where the crystallization step is carried out at 10-55 ° C for 5- 20 minutes. during the entire process in the reactors, mixing and flow of streams between the reactors is ensured, maintaining their uniformity. 2. The method according to p. The process according to claim 1, characterized in that the process is carried out in a cascade of 2-5 hydrolysis reactors, in each of which the process is carried out at a temperature of 80-100 ° C, for 2-25 minutes. 3. The method according to p. The process of claim 2, characterized in that the total time of the hydrolysis step is in the range 10-60 minutes. 4. The method according to p. The process of claim 1, characterized in that the flow of uniform streams between the reactors is forced by dosing the reactants into the hydrolysis reactor. 5. The method according to p. The process of claim 1, wherein the crystallization of the product is carried out at a temperature of 15 to 25 ° C, with a water: KDBW ratio = 2 to 6.