HU187240B - Process for producing 2 amino-ethana-sulfoacid and the 6-22 carbon atom n-acyl derivatives of this compounds - Google Patents

Abstract

The process according to the invention is carried out by reacting 2-taminoethanol with concentrated hydrochloric acid and then halogenating the 2-amoethanoborohydrochloride with thionyl chloride in an organic solvent medium, optionally returning the by-product hydrochloric acid to the initial reaction mixture, also as a by-product of sulfur. and the resulting 2-chloroethylamine hydrochloride is neutralized with alkali hydrogen carbonate and then reacted with potassium disulfite at a temperature of 80-120 ° C, and the pH is adjusted to 1 with hydrochloric acid. The resulting product is extracted with concentrated hydrochloric acid and, if desired, the resulting 2-aminoethane sulfonic acid is reacted with fatty acid chlorides to give N-acyl in a known manner. 187240 -1-

Description

The present invention relates to a process for the preparation of 2-aminoethane sulfonic acid and N-acyl derivatives thereof.

2-Aminoethane sulphonic acid (tauril) is one of the substances that influence the function of the liver. The N-acyl derivatives have a surfactant property and, as such, are used as detergent components, dispersants. In addition, taurine can be used as an intermediate in the production of other bioavailable substances.

The production of taurln has been dealt with since the middle of the last century. According to a known solution, Anzies Chem. Zentr. 82 H 1433 (1911)] is reacted with sulfonated chlorosulfonic acid and the resulting aldehyde ammonia or aldehyde imido derivative is reduced. This reaction is carried out with poor yield and the product thus obtained is highly contaminated.

According to a method used today Is (Shlck and Degerlng: Ind. Eng. Chem. 39, 906 (1947)) ethanolamine hydrochloride is chlorinated with tlonl chloride, and the 2-chloroethylamine hydrochloride formed is sodium sulfite or sodium hydrogen. with sulphite. This process yields a yield of 40-50%, but the resulting product contains 5-10% of the inorganic impurity.

N-acyl derivatives are prepared from fatty acid amides by water cleavage starting from hydroxyl ethanesulfonates. The disadvantage of this method is that many side reactions occur alongside the main reactor, as the reaction has to be carried out at 180-200 ° C.

A further disadvantage of the known solutions is that only recrystallized material can be obtained from crude taurine with a loss of 15-20%, which, however, is still not uniform according to chromatographic tests.

The process according to the invention is carried out by reacting 2-aminoethanol with concentrated hydrochloric acid, halogenating the resulting 2-amnoethanol hydrochloride with thionyl chloride in an organic solvent, optionally recycling the hydrochloric acid formed as a by-product to the starting reaction mixture and The dioxld is used in the next step, the 2-chloroethylammonium hydrochloride obtained is neutralized with alkaline hydrogencarbonate, then treated with potassium dibasulphite at 80120 ° C and the pH is adjusted to 1 with hydrochloric acid. extraction and, if desired, converting the 2 aminoethane sulfone bands thus obtained into the N-acyl derivative in known manner by reaction with fatty acid chlorine.

The process according to the invention has the advantage of starting from a relatively inexpensive starting material (technical grade ethanolamine). The process of the present invention can be carried out at low temperatures ranging from 0 to 100 ° C, with no byproduct and very favorable yield (7080%). The hydrochloric acid obtained in the second step of the synthesis is recycled to the first reaction step and the sulfur dioxide formed as a by-product in the second step of the synthesis is used as a reagent in the third step.

The process of the present invention involves the use of a hydrochloric acid wash which greatly enhances the purity of the product obtained. The process of the present invention provides a biologically active pure taurine which can be used for biological purposes.

The use of SO2 as a by-product makes it possible to significantly reduce the amount of gum disulfyl (K2S2O5) used.

The process according to the invention is very advantageous from an environmental point of view because it does not produce large amounts of difficult to remove by-products.

Scheme A illustrates the process of the invention.

The process of the present invention is illustrated by the following examples.

Example I

Preparation of 2-Amino-Ethanol Hydrochloride (Colamine.HCl) (cc. With hydrochloric acid)

Weigh 0.73 kg = 0.72 L (12.00 mol) of ethanolamine (kolamln) into a 3 L round bottom flask equipped with stirrer, thermometer, dispenser and ice-bath and stir under external melting ice-cooling (1.43 kg). = 1.20 I cc. HCl (fs = 1.19) was added at such a rate that the temperature of the reaction mixture did not rise above 40 ° C. The excess hydrochloric acid is distilled off (preferably under reduced pressure) and the product is dried to constant weight.

Yield: 1.13 kg (11.58 mol) of the title compound Mp = 80-82 ° C

96.50% based on ethanolamine (colamyl).

Example 2

Preparation of 2-chloroethylamine hydrochloride

In a 15 liter acid-proof apparatus (eg, round-bottomed flask or glass pear) equipped with a stirrer, thermometer, reflux condenser, dosing tube, CaClz, 1.13 kg (11.58 mole) of 2-amine-ethanol hydrochloride are added. and 3.45 kg = 2.32 L of anhydrous chloroform. The resulting suspension is added over thirty minutes with vigorous stirring

1.83 kg = 1.12 L (15.40 M) thionyl chloride

1.73 kg = 1.16 L of anhydrous chloroform. The reaction mixture was then stirred in an oil bath at 70 ° C for 2 hours, then 0.23 kg = 0.14 L (1.97 M) of thionyl chloride (1.38 kg = 0.93 L) in anhydrous chloroform was added and the mixture was stirred at 70 ° C. stir for 1 hour. After cooling, the solvent and excess thionyl chloride were distilled off and the crude product as distillation residue was 4.57 kg = 5.79 l abs. dissolved in boiling ethanol. 0.10 kg of activated carbon is added, the mixture is refluxed for 5 minutes, the carbon black is hot filtered and the filtrate is distilled to a volume of 1.70 L. After cooling, the crystalline product precipitated was filtered off, 0.47 kg = 0.60 L cold abs. washed with ethanol and dried to constant weight.

Yield: 1.32 kg (11.35 mol) of the title compound

145-146 ° C

98.01% based on 2-aminoethanol hydrochloride.

Example 3

Preparation of 2-aminoethane sulfonic acid (taurine)

In a 20 L acid proof apparatus (e.g. glass pear mixer) equipped with a stirrer, thermometer and reflux condenser, 1.32 kg (11.35 M) of 2-chloroethylamine hydrochloride are dissolved in 5.22 L of water at room temperature. Under vigorous stirring, 0.95 kg (11.35 moles) of sodium bicarbonate are added and the solution is added to the solution.

2.77 kg (12.38 M) of gum metabasulphite (vigorous foaming - if necessary, the solution is cooled in an external melting ice bath before addition). The resulting reaction mixture was stirred in a 100 ° oil bath for 8 hours and then evaporated to dryness (preferably under reduced pressure). To the distillation residue was added 6.81 L of hydrochloric acid and stirred vigorously for 30 minutes in a 100 ° oil bath (sulfur dioxide formed, strong foaming). The reaction mixture was filtered hot, and the white crystalline product remaining on the filter was boiled 3x1.70 L. wash with hydrochloric acid, combine the washings with the filtrate and distil to a volume of 4.50 L. Ethanol (4.50 L) was added and allowed to stand in a melting ice bath for two hours. The precipitated white crystalline crude product is filtered off, washed with 3 x 1.70 L of ethanol and dried to dryness. Weight of the crude product = 1.81 kg. Mp = 246-290 ° C (barnul). The crude product was dissolved in 10.20 L of 50% aqueous ethanol at reflux (if not completely soluble, filtered hot) and left overnight in the refrigerator. The snow-white needle-crystalline product was filtered, washed with ethanol and dried to constant weight.

Yield: 1.00 kg (7.99 moles) 0 D = 328-329 ° C

70.40% for 2-chloroethylamine hydrochloride and

66.58% based on ethanolamine (colamine).

Analysis

Elemental analysis IR, MMR and thin layer chromatography revealed the final product to be a single taurine.

(Merck DC-Plastlfollen, Kieselgel 6OF254; methanol: pyridine: water = 80; 0.5: 20; ninethylene spray Rr = 0.44). '

Example 4

Preparation of 2-chloroethylamine hydrochloride in a 1 L round bottom flask equipped with a Marcusson flask, dispenser, stirrer, thermometer, is charged with 1 L of toluene (benzene, xylene), 305 g (5 mol) of monoethanolamine.

405 mL (5 mol) cc was added under constant stirring and water cooling. hydrochloric acid at such a rate that the reaction temperature is maintained at 20-30 ° C.

After addition, the apparatus is heated to reflux (105 ° C) and the distillation water is separated off on Marcusson.

Azeotropic distillation is carried out until water is distilled from the system.

The resulting colamyl hydrochloride separates as an oily phase and crystallizes after cooling (m.p. 82-83 ° C).

To the resulting mixture was added a solution of 600 g of tlonl-chloride in 200 ml of toluene, with constant stirring. The released sulfur dioxide and hydrochloric acid are removed by a pump and reused.

After the addition, a half-hour post-treatment was performed at 50-60 ° C.

The resulting 2 chloroethylamine hydrochloride precipitates out of the system.

The remaining sulfur dioxide and hydrogen chloride gas in the solution were removed from the system using a slight vacuum.

It is convenient to dissolve the precipitated product in water without filtration as the next step (formation of sulfonic acid) is carried out in aqueous medium.

Water (1700 mL) was added to the toluene mixture and the product was dissolved and the lower aqueous layer was separated after 10 minutes. Filter perlite (20 g) was added to clarify, filtered and the aqueous clear filtrate was worked up to produce taurine.

The organic toluene phase can be reused for the preparation of 2-chloroethylamine hydrochloride.

In this way, without preparing the phase products, bypassing the distillation operations i

in one apparatus it is possible to prepare 2-chloroethylamine hydrochloride.

Example 5

Preparation of Taurin

While stirring, the aqueous solution is treated with sufficient sodium bicarbonate until pH 7 is reached. (about 50 g).

After reaching neutral pH, equimolar amount of sodium bicarbonate (420 g) was added, and after stirring for half an hour, 1160 g of potassium metabisulfite was added. There is strong foaming during the addition which can be reduced by keeping the temperature below + 10 ° C.

After addition, the mixture is stirred for 6 hours at reflux temperature by distilling water from the system for the last two hours.

After the reaction time, the mixture was cooled to room temperature and adjusted to pH 1 with HCl. (about 400 ml) After stirring for half an hour, the precipitated inorganic salts were filtered off (750 g) cc. wash with hydrochloric acid (100 mL). One liter of aqueous hydrochloric acid was distilled off from the clear filtrate.

For the remainder of the distillation, 1 liter of abs. alcohol was added and after stirring for 1 hour, the precipitated product was filtered off with 2x100 mL abs. wash with alcohol and dry.

Product weight: 680 g mp 250-53 ° C

By evaporation from the aqueous alcoholic filtrate additional valuable material can be obtained: weight:

g, m.p. 249-290 ° C

According to our studies, the filtered inorganic salts also contain valuable material. 10%.

Recrystallization of 15 g of the crude product yielded 10 g of 50% aqueous alcohol (80 ml).

In this way, 560 g of pure recrystallized product (757 g of crude product) is obtained, which is 80% of the theoretical yield based on monoethanolamine.

Quantities of substance needed to produce 500 g of taurine:

Toluene 1.20 liters of monoethanolamine 305 g cc. hydrochloric acid 1.00 liters

Tlonll-chloror 600 g

K2S2O5 1160 g

NaKCOa 500 g abs. Ethanol 3.50 liters

Example 6

Preparation of N-acyl-taurld

The operation is a 30-liter enameled, water-cooled

with steam, dosing, in a duplicator. Quantities of materials used: stirrer βΙ- Monoethanol -am 1 n 3.0 kg Toluene 8.66 kg Ο 0.01) Hydrochloric acid 11.00 kg Tionll chloride 6.00 kg Potassium metabiszulflt 11.5 kg Sodium hydroxide 40% 10.5 kg Kókuszzsírsavklorld 9.5 kg Sodium bicarbonate 4.5 kg

Preparation of monoethanolamine hydrochloride

Into a 30 L enameled doubler were added 3.0 kg of monoethanolamine, 10 L of toluene and 5 kg of cc. hydrochloric acid is added to the system with constant stirring and water cooling. The pH is checked at the end of the addition and, if it shows a value of 1, the water-cooling is stopped and then, with gentle steam heating, the apparatus is azeotropically stripped of the water present in the reactor.

If azeotropic distillation is not possible, vacuum distillation may be used.

The product was obtained as a yellow-brown viscous oil which crystallized at about 40 ° C.

Preparation of 1-chloroethylamine hydrochloride

To the toluene monoethanolamine hydrochloride solution obtained in the first phase, 6.0 kg of thionyl chloride is added under continuous stirring at a temperature such that the temperature does not exceed 50 ° C.

After addition, stirring is continued for 1 hour at 60 X using gentle steam heating.

The hydrogen chloride gas released during the reaction is absorbed by a water-ring vacuum pump

After the reaction was complete, the apparatus was cooled by cooling with water and water (20 L) was added. The stirrer was stopped and after 15 minutes the valuable lower aqueous phase was separated. The upper toluene phase is stored in a plastic balloon (reusable).

Preparation of ethylamine sulfonic acid

The aqueous solution was re-fed to the 30 L and neutralized with sodium bicarbonate with constant stirring. To the neutralized solution was repeatedly added an equivalent of NaHCO3 (4 kg).

Then proceed with cautious addition of potassium metabisulfite (11.5 kg), which will take 4-5 hours. After addition, it is heated to reflux and stirred for 8 hours at this temperature.

At the end of the reaction time, the reaction mixture was cooled and adjusted to pH 1 with hydrochloric acid (6 kg). The liberated sulfur dloxld and hydrochloric acid gas are absorbed by a water-ring vacuum pump.

Preparation of coconut fatty acid tauride

The aqueous solution was neutralized with 40% industrial alkaline solution (about 1 kg) and then 5 kg of alkaline solution was added. Switching on the device with cold cooling, we begin to add coconut fatty acid chloride (9.5 kg) through a diving tube at a rate such that the temperature does not rise above 30 ° C.

The pH was maintained at about 10 by parallel addition of 40% industrial alkaline solution. Required amount 4.5 kg.

The target product precipitates in crystalline form. The resulting slurry was post-stirred for 1 hour after addition (2 hours), filtered through a pellet, dried in a dryer at 40 ° C and packaged.

Quantity received: 17 kg.

The product contained 48% active ingredient.

Claims (1)

Process for the preparation of 2-aminoethanesulfonic acid and N-acyl derivatives of this compound having from 6 to 22 carbon atoms, characterized by reacting 2-aminoethanol with concentrated hydrochloric acid followed by thionyl-2-aminoethanol hydrochloride in an organic solvent medium. halogenated with chlorine, optionally the by-product hydrochloric acid is recycled to the starting reaction mixture, and the sulfur dioxide also obtained as a by-product The reaction mixture was used in the third reaction step, the 2-chloroethylamine hydrochloride obtained was neutralized with alkali hydrogen carbonate, treated with potassium disulfite at 80-120 ° C, and The hydrochloride is adjusted to 1 with 30 hydrochloric acid and the resulting product is extracted with concentrated hydrochloric acid and, if desired, is reacted with the fatty acid chlorides to give the N-acyl derivative. 35 over.