DE2232090A1 - METHOD FOR MANUFACTURING BETA-ALANINE - Google Patents

Description

Tokyo Fine Chemical Co., Ltd. Osaka Bldg., 1-chöme, Uchisaiwaicho; Chiyoda-ku, Tokyo, Japan

Process for the production of β-alanine

The invention relates to a process for the production of β-alanine by reaction of acrylic acid or an acrylic ester with ammonia. For the production of ß-alanine, which is used as a raw material for the production of certain drugs and the like, several methods have heretofore been proposed. One of the procedures that are required for the industry in terms of Raw materials as well as on the reaction conditions is advantageous, relies on the reaction of acrylic acid and / or Acrylic esters with ammonia at relatively high temperatures and pressures (see for example the American patent No. 2,376,334, English patent 561,013, Journal of Org. Chem.No. 26 p. 262 (1961)).

In this known process, large amounts of 3,3'-iminodiopropionic acid are used (hereinafter referred to as IDPA) together with the

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ß-alanine is formed. This reduces the formation of β-alanine and limits the yield to 40% of the theoretical value in relation to the acrylic acid and / or acrylic ester starting materials. Since IDPA usually contains some amount of ammonia salt, the IDPA referred to herein also contains the monoamone salt.

The object of the invention is to provide a method of the type mentioned at the beginning Kind of designed so that the yield of ß-alanine is as high as possible. The invention is characterized in that by Addition of carbonate of ammonia and / or addition of gaseous carbon dioxide brings about a carbonate ion content in the reaction mixture in the absence of 3,3'-iminodiporpionic acid in the reaction mixture to values between 0.5 and 1.5 mol per mol of acrylic acid or acrylic ester and in the presence of 3,3'-iminodiporpionic acid in the reaction mixture to values between 0.5 and 1.5 moles per mole of acrylic acid or acrylic ester plus 0.5 to 1.5 moles per mole of 3,3'-iminodiporpionic acid.

According to the invention, the formation of IDPA and other by-products inhibited in favor of the yield of ß-alanine. If IDPA is already in the starting mixture - i.e. the mixture of which the reaction takes place assumes - included, then this IDPA is ί according to the invention at least partially converted into ß-alanine and this also increases the ß-alanine yield.

The above-mentioned known method is believed to be followed by the following Stages expires

«GHCOOR + NH ₃ => NHgCHgCHgCOOR ¹ (i)

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NH ₀ CH ₀ CH ₀ COOR ¹ + CH ₀ = CHCOOR

CH ₂ CH ₂ COOR ¹

NH <\

CH ₂ CH ₂ COOH

(II)

CH ₂ CH ₂ COOR ¹ CH ₂ CH ₂ COOH

+ NH

2NH ₂ CH ₂ CH ₂ COOR ¹

(ill)

CH ₀ CH ₀ COONH

2NH ₂ CH ₂ CH ₂ COOH

(IV)

CH ₂ CH ₂ COOH

R denotes hydrogen, CH ₃ or C ₃ H ₅ and R- ¹ denotes hydrogen or NH _4. Of the indicated reaction stages, stages III and IV appear to be in equilibrium.

The invention is based on the following considerations. Unless the. Reaction II is inhibited and the equilibria of reaction III and IV proceed in the right direction, ß-alanine can obviously be produced in large quantities. It can therefore be assumed that the high yields _{can be generated under the protection of the amino group (NH 2} ) of the β-alanine formed by the reaction. For this reason, attempts have been made with the addition of carbonate of ammonia and / or with the introduction of gaseous CO ₀ into the starting mixture, which comprises acrylic acid and / or acrylic esters and ammonia. It has been suggested that carbon ions _{generated in solutions containing carbonate of ammonia and / or CO 2} add β-alanine to the amino group through the reaction and protect the amino group as in Example V and inhibit the formation of by-products. Appropriate tests worked as expected and ß-alanine was obtained with excellent yields.

Herein lies a possible explanation for the fact that the formation of

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By-products in acrylic acid and / or acrylic ester with ammonia according to the invention is noticeably inhibited and IDPA that has been formed or was originally present in the reaction mixture is converted into ß-alanine and the ß-alanine with high yields by adding carbonate of ammonia and / or Introduction of CO ₂ into the mixture can be obtained:

+ H
NH ₂ CH ₂ CH ₂ COOR ¹

⁰ Vv '' (V)

^N NH ₂ CH ₂ CH ₂ C00R '

+ H

Carbonic acid ammonia that are added to the starting mixture are, for example, ammonium carbonate, ammonium hydrogen carbonate (ammonium bicarbonate) and ammonium hydrogen carbonate carbamate. Instead of carbonate of ammonia, it is also possible to _{add gaseous COp or carbonate of ammonia together with gaseous CO 2 in} order to achieve the desired effects if the added proportions are kept within the specified limits. In particular, a large excess of gaseous CO ₂ beyond the stated quantity ranges should be avoided because this can result in a reduction in the ß-alanine yield and also a deterioration in the ß-alanine produced.

If IDPA is added to the starting mixture of acrylic acid and / or acrylic ester with ammonia, then this amount should be based on weight make up between 0.5 and 5 parts IDPA to one part acrylic acid and / or acrylic ester.

The concentrations of ammonia that are used in the individual cases are, if possible, 20 % and above, and are preferably 20 to 25 %. More concentrated ammonia

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but can also be used »'

The amounts of ammonia used should amount to 5 mol or more per 1 mol of acrylic acid and / or acrylic ester and, in addition, should be 5 moles of ammonia or more required for 1 mole of IDFA, (calculated as 3rd, 3 iminodipropionic acid). *

According to the invention, the preferred reaction temperature is 100 to 200 degrees Celsius, in particular 150 degrees to 200 degrees Celsius. The reaction times are 1 to 5 hours and pressures can be any after the heating.

Water, ammonia and carbonic acid are preferably converted into ammonia in vacuo by distillation from the reaction mixture obtained segregated. The remainder is treated with methanol and crystallized. This gives β-alanine in excellent condition and with high yield without the need for complicated procedures such as Hydrolysis, desalination by ion exchangers or recrystallizations have to be used.

The mother liquor contains after isolation of the ß-alanine by a such a procedure a large amount of IDPA, which is not yet in ß-alanine is converted. If! Solvent in the mother liquor in a vacuum " separated by distillation, IDPA remains as a residue and can be used as a raw material for the next reaction without further treatment. For this reason, at Circulation of the IDPA a continuous production of ß-alanine possible. If the reaction conditions are maintained at all times, the amounts of β-alanine obtained after the separation consistently correspond to the amount previously added to the reaction system and ß-alanine can be used in unsurpassable quantities can be produced with easy handling. *

It is desirable that acrylic acid and / or acrylic esters, ammonia, carbonate of ammonia, gaseous CO ₂ and IDPA, respectively

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are always added to the starting mixture in constant quantities

When IDPA is circulated for the process for producing β-alanine without using the invention, that is, without carbonate of ammonia and / or gaseous CO ₂ , the by-product IDPA will accumulate in the circulation system. Thus, the yield of β-alanine decreases and crystal formation becomes difficult.

The invention thus makes it possible, firstly, to utilize IDPA completely and effectively, and secondly, a high yield - almost '. 100 % - to achieve ß-alanine and thirdly this with a simple manufacturing process, which fourthly can be operated continuously with circulation of the IDPA.

The invention is illustrated in more detail by means of examples. In the examples, all parts and percentages are to be understood as being based on weight, unless stated otherwise.

Example ι

A mixture of 24.4 parts of methyl acrylate (with 200 ppm hydrochione), 240 parts of 25 % ammonia and 25 parts of carbonate of ammonia was heated to 160 ° C. for 4 hours in an autoclave and then allowed to cool to room temperature. The reaction mixture was treated with activated charcoal and heated to 60 ° C. under reduced pressure on a water bath to remove water ammonia, carbonate ammonia and methanol generated by the reaction. Syrup was obtained in an amount of 25.5 parts as a residue. The syrup was mixed with 70 parts of methanol and dissolved. The mixture was allowed to stand at room temperature to produce crystals,

The mixture containing the crystals was heated to reflux temperature for one hour on a water bath and set to Ziramer-309883/1391

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let the temperature cool down. The crystals "were filtered out, washed with a little methanol and dried in vacuo. 18 parts of white crystalline β-alanine were obtained.

Example 2

A mixture of 26.2 parts acrylic acid, (containing 200 ppm Methoxyhydroquinone), 225 parts of 28% ammonia and 47 parts Commercial carbonate of ammonia was heated to 180 ° C for 3 hours in an autoclave and then allowed to cool up to room temperature. The reaction mixture was then treated with activated charcoal and heated on a water bath in vacuo, to remove water, ammonia and carbonic acid ammonia by distillation that were present in the mixture. Syrup was obtained in an amount of 32.5 parts. The syrup was mixed with 80 parts of methanol and dissolved. The mixture was as in Example 1 is treated. 23 parts of white crystal were obtained! nes ß-alanine. The melting point is 198 ^ 200 ° C.

Example 3

A mixture of 20 parts of acrylic acid (which contained 200 ppm methoxyhydroquinone), 228 parts of 28% strength ammonia, 27 parts of syrupy IDPA and. 37 parts of ammonia hydrogen carbonate were heated to 160 ° C. for 4 hours in an autoclave and then allowed to cool to room temperature. The reaction mixture was decolorized with activated charcoal and heated on a water bath in vacuum to remove water, ammonia, and carbonic acid ammonia present in the mixture by distillation. The amount of syrup obtained was 54 parts. The syrup was mixed with 150 parts of methanol and dissolved. The mixture was treated as indicated in Example 1. 23.5 parts of white crystalline β-alanine were obtained, which corresponded to a theoretical yield of 95% based on the acrylic acid supplied. The melting point is 198 ** 200 ⁰ C.

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On the other hand, after the crystalline β-alanine had been removed, the mother liquor became methanol by distillation centrifuged and 31 parts of syrupy IDPA were recovered.

Example 4

A mixture of 25% ammonia, IDPA, and carbonate of ammonia and acrylic acid in a ratio of 12.6: 2.84 ' 2.48: 1 was continuously fed to a 4 liter high pressure continuous reactor using a positive displacement pump at 160. During the reaction, the residence time of the mixture was adjusted to up to 2.5 hours. From the reaction mixture, which was let out of the reactor after operating for 6 hours, 1.6 liters was concentrated in vacuo to give 373 grams of syrup as a residue. The syrup was mixed with 1.2 liters of methanol and dissolved. The mixture was allowed to stand at room temperature to generate crystals. The mixture containing the crystals was heated in a water bath at a reflux temperature for one hour and then cooled to room temperature. The crystals were filtered out, washed with a little methanol and dried at a temperature of 60 ° C. in vacuo. 111.5 grams of white crystalline β-alanine were obtained which, based on the acrylic acid fed in, corresponded to 98.3% of the theoretical value. The melting point is 198- 200 ⁰ C.

On the other hand, the methanol was removed from the mother liquor after removal of the crystals of ß-alanine separated by filter by distillation and 262 grams of syrupy IDPA was used as Residue recovered.

Example 5

A mixture of 30 parts of ethyl acrylate (which contains 200 ppm of hydroquinone

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contained), 225 parts of 25 % ammonia were placed in an autoclave and then 14 parts of gaseous CO _{2 were introduced} into the autoclave at 20 ^° C. under high pressure of 8 ^l at. The mixture was gradually heated to 1 50 ⁰ C and maintained at that tempera- "■ ρeratür for 4 hours. Then allowed to cool the mixture to room temperature. It was then decolorized with activated carbon and heated in vacuo from a water bath to 60 C to remove water generated by the reaction, ammonia, carbonic ammonia and ethanol by distillation to obtain 26.5 parts of syrup as a residue. The syrup was mixed with 72 parts of methanol and dissolved, and the mixture was allowed to stand at room temperature to admit crystals The mixture containing the crystals was heated to reflux temperature for one hour and cooled. The crystals were filtered out, washed with a little methanol and dried in vacuo at 60 ° C. 19 parts of white crystalline β-alanine were obtained, which is a theoretical A yield of 71 % in relation to the ethyl acrylate fed in. The melting point is 198 * ^ <199 ° C.

Example 6 . '

A mixture of 22 parts of acrylic acid (which contained 200 ppm methoxyhydroquinone) and 225 parts of 25 % ammonia were placed in an autoclave and _{18 parts of gaseous CO 2} were then introduced into the autoclave at 20 ° C. under a pressure of 8 atmospheres. The mixture was gradually heated to 160 ° C. and held at that temperature for 3 hours. The mixture was allowed to cool to room temperature and treated with activated charcoal. The mixture was then heated to 60 ° C. in vacuo on a water bath in order to remove water, ammonia and carbonate of ammonia by distillation. So you got 27 parts of syrup . The syrup was mixed with 72 parts of methanol and treated according to the procedure described in Example 1. One received

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19 parts of white crystalline ß-alanine, which is a theoretical. Yield of 71.7 # in terms of acrylic acid fed.

Example 7

A mixture of 24.4 parts of methyl acrylate (which contained 200 ppm of hydroquinone), 225 parts of 25% ammonia and 25 parts of IDPA were placed in an autoclave and then 14 parts of gaseous CO _{2 were added} at a temperature of 20 ° under a pressure of 8 atm introduced into the autoclave. The mixture was gradually heated to 150 ° C and held at that temperature for 3 hours. The reaction mixture was allowed to cool to room temperature and treated with activated charcoal. It was then heated on a water bath to 60 ^° C. in vacuo in order to remove water, ammonia, carbonic acid ammonia and methanol generated in the reaction by distillation. 50 parts of syrup were thus obtained as a residue. The syrup was mixed and dissolved with 120 parts of methanol, and then allowed to stand at room temperature to generate crystals. The mixture containing the crystals was refluxed on a water bath for one hour and cooled to room temperature. The crystals were sieved out, washed with a little methanol and dried in vacuo. 23.5 parts of white crystalline β-alanine were obtained, which corresponded to a theoretical yield of 93% in relation to the methyl acrylate fed in.

On the other hand, the mother liquor after the separation of the ß \ alanine was concentrated in vacuo to 26 parts syrupy IDPA to the methanol by distillation '■ to remove, so were recovered as a residue.

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Example 8

A mixture of 19 parts of acrylic acid (which contained 200 ppm methoxyhydroquinone), 225 parts of 25% ammonia and 26 parts of syrupy IDPA, which was recovered according to Example 7, were placed in an autoclave and then 14 parts of gaseous CO ₂ under a pressure of 8 atmospheres The mixture was gradually heated and held at 160 ° C for 4 hours. The reaction mixture was allowed to cool to room temperature and treated as in Example 3, resulting in 50.5 parts of syrup. The syrup was mixed and dissolved with 120 parts of methanol and then allowed to stand at room temperature to make crystals. Treatment of the crystals as in Example 7 gave 22 parts of white, crystalline β-alanine, which corresponded to a theoretical yield of 93.5% in relation to the acrylic acid fed. The melting point is 198 * - * 200 ° C.

On the other hand, after removing the β-alanine, the mother liquor was treated as in Example 3 and 27.5 parts of syrupy IDPA became regained.

Example 9

A solution of 28% ammonia, IDPA and acrylic acid in a ratio of 12: 2.8: 1 by weight was continuously introduced at a temperature of 150 ° C. into a continuous high pressure reactor at 150 ° C. by means of a positive displacement pump so that it remained there for 3 hours. At the same time, gaseous CO _{2 was} continuously introduced into the reactor at 20 ^° C. and 40 atm. In a ratio of 1.5 1 part of acrylic acid. Of the reaction mixture let out of the reactor after 4 hours of operation, 1.33 liters were divided off and concentrated in vacuo.

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The residue was 308 grams of syrup. The syrup was mixed with one liter of methanol and dissolved. The mixture was left stand at room temperature and a white crystalline solid formed. The solid was as in the example 7 is treated. 94.5 grams of white, crystalline β-alanine were obtained, which was 97.7% of the theoretical yield in relation to the acrylic acid supplied. The melting point is 197 ~ 200 ° C.

On the other hand, after removing the ß-alanine, the mother liquor was as indicated in Example 7, and 213 grams of syrupy IDPA were recovered.

Example 10

A mixture of 25% ammonia, IDPA, commercially available carbonate of ammonia and acrylic acid in a ratio of 22: 2.86: 2: 1 by weight was continuously introduced at a temperature of 150 ° C. into a continuous high-pressure reactor by means of a positive displacement pump, so that it was there 3 hours remained. At the same time, gaseous CO ₂ at 20 ° C. and 40 atm. Was continuously introduced into the reactor in a ratio of 0.3 part to one part of acrylic acid. Two liters of the reaction mixture let out of the reactor after 4 hours of operation were divided off and concentrated in vacuo. The residue left 446 grams of syrup. The syrup was mixed and dissolved with 1.7 liters of methanol. The mixture was allowed to stand at room temperature and a white crystalline solid formed. The solid was treated as indicated in Example 7. 132 grams of white crystalline β-alanine were obtained, which corresponds to 98 % of the theoretical yield in relation to the acrylic acid fed in.

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spoke. The melting point is 198 "-" 200 C.

On the other hand, the mother liquor after the separation of the β-alanine treated as indicated in Example 7, and 314 grams of syrupy IDPA remained as a residue.

The nitrogen analyzes of the β-alanine obtained in the above examples are shown in the table below
laid down.

No. of
Example 1 - 2 3 4th 5 6th 7th 8th nitrogen
salary in % 15.58 15.60 15.60 15.74 15.62 15.78 15.57 15.72

No. of
Example 9 1Θ nitrogen
salary in % 15.68 15.70

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Claims (3)

P 30 906 28.6. 72 EXPECTATIONS .! Process for the preparation of β-alanine by the reaction of Acrylic acid or an acrylic ester with ammonia, characterized in that by adding carbonate of ammonia and / or addition of gaseous carbon dioxide a carbonate ion content is brought about in the reaction mixture in the absence of 3,3'-iminodiporpionic acid in the reaction mixture to values between 0.5 and 1.5 moles per mole of acrylic acid or acrylic ester and in the presence of 3,3'-iminodiporpionic acid in the reaction mixture to values between 0.5 and 1.5 mol per mol of acrylic acid or acrylic ester plus 0.5 to 1.5 moles per mole of 3.3 '* iminodiporpionic acid. 2. The method according to claim 1, characterized in that the starting mixture ■ 0.5 to 5 parts by weight of 3,3'-iminodiporpionic acid per 1 part of acrylic acid or acrylic ester are added. 3. The method according to claim 1 or 2, characterized in that .the reaction is carried out at a temperature between 100 and 200 degrees Celsius and for a period of 1 to 5 hours . 309883/1391 - S - ■■ P 30 906 4. Process according to one of the preceding claims, characterized in that the 3,3 'iminodiporpionic acid is circulated in that it is formed from the reaction. Mother liquor
isolated and added to a new starting mixture again. 3 0 9883/1391