JPS6258347B2 - - Google Patents
Info
- Publication number
- JPS6258347B2 JPS6258347B2 JP54159250A JP15925079A JPS6258347B2 JP S6258347 B2 JPS6258347 B2 JP S6258347B2 JP 54159250 A JP54159250 A JP 54159250A JP 15925079 A JP15925079 A JP 15925079A JP S6258347 B2 JPS6258347 B2 JP S6258347B2
- Authority
- JP
- Japan
- Prior art keywords
- aziridine
- carboxylic acid
- exchange resin
- serine
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- MTCFGRXMJLQNBG-UHFFFAOYSA-N serine Chemical compound OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 39
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- WBGBOXYJYPVLQJ-UHFFFAOYSA-N aziridine-2-carboxylic acid Chemical compound OC(=O)C1CN1 WBGBOXYJYPVLQJ-UHFFFAOYSA-N 0.000 claims description 21
- 230000002378 acidificating effect Effects 0.000 claims description 13
- 239000003729 cation exchange resin Substances 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000003456 ion exchange resin Substances 0.000 description 19
- 229920003303 ion-exchange polymer Polymers 0.000 description 19
- 238000000034 method Methods 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 229960001153 serine Drugs 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- -1 alkaline earth metal salt Chemical class 0.000 description 10
- 150000001340 alkali metals Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 6
- ZGQWDLXRNCMIHH-UHFFFAOYSA-M lithium;aziridine-2-carboxylate Chemical compound [Li+].[O-]C(=O)C1CN1 ZGQWDLXRNCMIHH-UHFFFAOYSA-M 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- FJAWVRZITFCHEK-UHFFFAOYSA-M sodium;aziridine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CN1 FJAWVRZITFCHEK-UHFFFAOYSA-M 0.000 description 3
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- MQHYSRLAEFWPQR-UHFFFAOYSA-N propan-2-yl aziridine-2-carboxylate Chemical compound CC(C)OC(=O)C1CN1 MQHYSRLAEFWPQR-UHFFFAOYSA-N 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GJMPSRSMBJLKKB-UHFFFAOYSA-N 3-methylphenylacetic acid Chemical compound CC1=CC=CC(CC(O)=O)=C1 GJMPSRSMBJLKKB-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 description 1
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
- 229930195711 D-Serine Natural products 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 229940023913 cation exchange resins Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960003077 cycloserine Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- HKRZTXMFJABEOO-UHFFFAOYSA-N ethyl 3-amino-2-chloropropanoate;hydrochloride Chemical compound Cl.CCOC(=O)C(Cl)CN HKRZTXMFJABEOO-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940117957 triethanolamine hydrochloride Drugs 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
【発明の詳細な説明】
本発明はDL−セリンの新規な製造方法に関す
るものであり、さらに詳しくは、アジリジン−２
−カルボン酸またはそのアルカリ金属もしくはア
ルカリ土類金属塩の水溶液を強酸性型カチオン交
換樹脂に通してアジリジン−２−カルボン酸を吸
着させ、引きつづいて該イオン交換樹脂を加熱す
ることによつてDL−セリンを製造する方法に関
するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing DL-serine, more specifically, aziridine-2
- DL by passing an aqueous solution of a carboxylic acid or its alkali metal or alkaline earth metal salt through a strongly acidic cation exchange resin to adsorb aziridine-2-carboxylic acid, and subsequently heating the ion exchange resin. - A method for producing serine.
セリンはα−アミノ酸の一種であり、その光学
活性体のＬ−セリンがアミノ酸輸液として、また
Ｄ−セリンが抗生物質のシクロセリンの原料とし
て有用な化合物である。また、セリンは飼料添加
剤として将来的にその伸長が期待されているＬ−
トリプトフアンを、酵素法により製造する方法で
の原料として有用視されている化合物でもある。
従来、セリンの製法については種々の方法が提案
されているが、それぞれ一長一短があり、工業的
に満足し得る製法は見当らない。 Serine is a type of α-amino acid, and its optically active form, L-serine, is a compound useful as an amino acid infusion, and D-serine is a compound useful as a raw material for the antibiotic cycloserine. In addition, serine is a feed additive that is expected to grow in the future.
It is also a compound that is considered useful as a raw material in a method for producing tryptophan using an enzymatic method.
Conventionally, various methods have been proposed for producing serine, but each has advantages and disadvantages, and no production method that is industrially satisfactory has been found.
本発明者らは、比較的容易に製造できるアジリ
ジン−２−カルボン酸またはそのアルカリ金属も
しくはアルカリ土類金属塩からDL−セリンを製
造する方法を鋭意検討した結果、アジリジン−２
−カルボン酸を強酸性型カチオン交換樹脂に吸着
させたのち、このイオン交換樹脂を加熱すること
によつて工業的に有利にDL−セリンを製造する
方法を見出し、本発明を完成するに至つた。 The present inventors have conducted intensive studies on a method for producing DL-serine from aziridine-2-carboxylic acid or its alkali metal or alkaline earth metal salt, which can be produced relatively easily.
- Discovered an industrially advantageous method for producing DL-serine by adsorbing carboxylic acid onto a strongly acidic cation exchange resin and then heating this ion exchange resin, leading to the completion of the present invention. .
すなわち、本発明の方法は、アジリジン−２−
カルボン酸を強酸性型のカチオン交換樹脂に吸着
させ、吸着状態のままで加熱して加水分解してセ
リンを得る方法である。 That is, the method of the present invention provides aziridine-2-
In this method, carboxylic acid is adsorbed onto a strongly acidic cation exchange resin, and the adsorbed state is heated and hydrolyzed to obtain serine.
従来、アジリジン−２−カルボン酸からDL−
セリンを製造する方法については、アジリジン−
２−カルボン酸リチウム塩を15％硫酸中で処理す
る方法（K.D.Gundermann，Chem.Ber.，93，
1639（1960））が知られているに過ぎない。しか
しながら、この方法では硫酸使用量が原料アジリ
ジン−２−カルボン酸リチウム塩に対して大過剰
（約12モル比）を要し、また反応後、生成したセ
リンを反応系より単離するためには、過剰の硫酸
を水酸化カルシウムまたは水酸化バリウムで中和
し、硫酸カルシウムまたは硫酸バリウムの形で沈
澱させて別分離する必要があり、工程が煩雑と
なる欠点を有するとともに、反応の容積効率も良
くない。また、アジリジン−２−カルボン酸の硫
酸中での加水分解においては、反応系に水より高
い求核能を有する陰イオン、例えば、ハロゲンイ
オンが共存すると副生物としてそれらのイオンが
付加した化合物が生成して、DL−セリン収率を
低下させる欠点も有する。これに対して、本発明
の方法は、従来、全く知られていない新規な方法
であり、上記の硫酸中での加水分解に比較して、
工程が著しく簡略化され、ほとんど副生物を伴う
こともなく、アジリジン−２−カルボン酸に対し
て高収率でDL−セリンが得られる利点がある。
さらには、反応によつて生成したDL−セリンの
単離は加熱後の該イオン交換樹脂にアンモニア水
を流してDL−セリンを溶離し、溶離液を濃縮乾
固するか、または濃縮後晶析するだけでよく、こ
のことも本発明方法の特徴の一つである。 Conventionally, DL- from aziridine-2-carboxylic acid
For the method of producing serine, see aziridine-
A method of treating 2-carboxylic acid lithium salt in 15% sulfuric acid (KDGundermann, Chem.Ber., 93 ,
1639 (1960)) is only known. However, in this method, the amount of sulfuric acid used must be in large excess (approximately 12 molar ratio) to the raw material aziridine-2-carboxylic acid lithium salt, and after the reaction, it is necessary to isolate the serine produced from the reaction system. , it is necessary to neutralize excess sulfuric acid with calcium hydroxide or barium hydroxide, precipitate it in the form of calcium sulfate or barium sulfate, and separate it separately, which has the disadvantage of complicating the process and reducing the volumetric efficiency of the reaction. not good. In addition, in the hydrolysis of aziridine-2-carboxylic acid in sulfuric acid, if anions with a higher nucleophilic ability than water, such as halogen ions, coexist in the reaction system, compounds to which these ions are added are produced as by-products. However, it also has the disadvantage of reducing the yield of DL-serine. In contrast, the method of the present invention is a novel method that has not been previously known, and compared to the above-mentioned hydrolysis in sulfuric acid,
It has the advantage that the process is significantly simplified, almost no by-products are produced, and DL-serine can be obtained in high yield relative to aziridine-2-carboxylic acid.
Furthermore, DL-serine produced by the reaction can be isolated by flowing ammonia water through the heated ion exchange resin to elute DL-serine, and concentrating the eluate to dryness, or by crystallizing it after concentration. This is also one of the features of the method of the present invention.
本発明の方法で使用される原料のアジリジン−
２−カルボン酸またはそのアルカリ金属もしくは
アルカリ土類金属塩は、α，β−ジブロムプロピ
オン酸アルキルエステルと液体アンモニアとの反
応によつて得られるアジリジン−２−カルボン酸
アルキルエステルをアルカリ金属またはアルカリ
土類金属で処理する公知の方法（K.D.
Gundermann，Chem.Ber.，93，1639（1960）：
E.Kyburz，Helv.Chim.Acta.，49，368
（1966））またはそれに準じた方法で製造できる。
このような公知方法で製造されたアジリジン−２
−カルボン酸塩を原料として使用するのに特に単
離する必要はなく、アジリジン−２−カルボン酸
アルキルエステルの加水分解後の水溶液、例え
ば、α，β−ジブロムプロピオン酸イソプロピル
エステルと液体アンモニアとから得られるアジリ
ジン−２−カルボン酸イソプロピルエステルをエ
タノールと水との混合溶媒中、水酸化ナトリウム
で加水分解しアルコールを減圧下に留去すること
によつて得られるアジリジン−２−カルボン酸ナ
トリウムの水溶液、あるいは、同様の方法で得ら
れる他のアルカリ金属またはアルカリ土類金属塩
の水溶液を使用することもできる。 Aziridine, the raw material used in the method of the present invention
2-carboxylic acid or its alkali metal or alkaline earth metal salt is an alkyl aziridine-2-carboxylic acid obtained by the reaction of α,β-dibromopropionic acid alkyl ester with liquid ammonia. Known methods of processing with earth metals (KD
Gundermann, Chem. Ber., 93 , 1639 (1960):
E.Kyburz, Helv.Chim.Acta., 49 , 368
(1966)) or a similar method.
Aziridine-2 produced by such a known method
- There is no need to isolate the carboxylic acid salt in order to use it as a raw material, and an aqueous solution of aziridine-2-carboxylic acid alkyl ester after hydrolysis, for example, α,β-dibromopropionate isopropyl ester and liquid ammonia Aziridine-2-carboxylic acid isopropyl ester obtained from aziridine-2-carboxylic acid isopropyl ester is hydrolyzed with sodium hydroxide in a mixed solvent of ethanol and water, and the alcohol is distilled off under reduced pressure. It is also possible to use aqueous solutions or solutions of other alkali metal or alkaline earth metal salts obtained in a similar manner.
本発明の方法を実施するには、まずアジリジン
−２−カルボン酸またはそのアルカリ金属もしく
はアルカリ土類金属塩の水溶液を強酸性型カチオ
ン交換樹脂に通し、さらに純水を通して、アジリ
ジン−２−カルボン酸を該イオン交換樹脂に吸着
せしめる。この場合、アジリジン−２−カルボン
酸またはその金属塩の水溶液はメタノール、エタ
ノール等の水と混和する有機溶媒を含有していて
も何ら差し支えない。 To carry out the method of the present invention, first, an aqueous solution of aziridine-2-carboxylic acid or its alkali metal or alkaline earth metal salt is passed through a strongly acidic cation exchange resin, and then purified water is passed through a solution of aziridine-2-carboxylic acid or an alkali metal or alkaline earth metal salt. is adsorbed onto the ion exchange resin. In this case, the aqueous solution of aziridine-2-carboxylic acid or its metal salt may contain an organic solvent miscible with water, such as methanol or ethanol.
使用する強酸性型カチオン交換樹脂はＨ型、
Na型、またはNH4型等いずれの型でもよいが、
通常、Ｈ型で使用するのが好ましい。またイオン
交換樹脂の基体はゲル型、ポーラス型またはマク
ロポーラス型等あらゆる基体のものを使用するこ
とができる。したがつて、強酸性型カチオン交換
樹脂であればその銘柄は特に限定されるものでは
ない。また、２銘柄以上の強酸性型カチオン交換
樹脂を併用することも何ら差支えない。イオン交
換樹脂の使用量はアジリジン−２−カルボン酸な
らびにその水溶液中に共存するアルカリ金属また
はアルカリ土類金属イオンとの総和量に対して、
湿潤状態での交換容量で１当量以上、好ましくは
1.2当量以上である。例えば、１モルのアジリジ
ン−２−カルボン酸ナトリウムを原料とし、総交
換容量が2.0meq／mlの強酸性型カチオン交換樹
脂を使用する場合、その樹脂使用量は１以上、
好ましくは1.2以上である。樹脂量が少ないと
アジリジン−２−カルボン酸の漏出が起こる。 The strongly acidic cation exchange resin used is H type,
It can be either Na type or NH4 type, but
Usually, it is preferable to use the H type. Further, the base of the ion exchange resin can be of any type such as gel type, porous type, or macroporous type. Therefore, the brand is not particularly limited as long as it is a strongly acidic cation exchange resin. Furthermore, there is no problem in using two or more brands of strongly acidic cation exchange resins together. The amount of ion exchange resin used is based on the total amount of aziridine-2-carboxylic acid and the alkali metal or alkaline earth metal ions coexisting in the aqueous solution.
1 equivalent or more in terms of wet exchange capacity, preferably
It is 1.2 equivalent or more. For example, when using a strongly acidic cation exchange resin using 1 mol of sodium aziridine-2-carboxylate as a raw material and having a total exchange capacity of 2.0 meq/ml, the amount of resin used is 1 or more,
Preferably it is 1.2 or more. If the amount of resin is small, leakage of aziridine-2-carboxylic acid will occur.
本発明の方法において、アジリジン−２−カル
ボン酸を強酸性型カチオン交換樹脂に吸着させる
には、通常、イオン交換樹脂を充填したカラムに
アジリジン−２−カルボン酸の水溶液をアルカリ
性のまま通すか、あるいは希塩酸または希硫酸等
で中和して、中性または弱酸性のいずれかの状態
で通し、さらに純水を通してやればよい。この際
アジリジン−２−カルボン酸水溶液中のアジリジ
ン−２−カルボン酸の濃度には特に限定はない。 In the method of the present invention, in order to adsorb aziridine-2-carboxylic acid onto a strongly acidic cation exchange resin, an aqueous solution of aziridine-2-carboxylic acid is usually passed through a column packed with an ion exchange resin while remaining alkaline; Alternatively, the solution may be neutralized with dilute hydrochloric acid or dilute sulfuric acid, passed in either a neutral or weakly acidic state, and then purified water may be passed through. At this time, there is no particular limitation on the concentration of aziridine-2-carboxylic acid in the aqueous aziridine-2-carboxylic acid solution.
前記のように、アジリジン−２−カルボン酸を
吸着させた強酸性型カチオン交換樹脂は湿潤状態
で加熱される。その加熱方法には、特に限定はな
いが、湿潤状態、すなわち水の存在下に加熱する
必要がある。例えば、加熱された水をイオン交換
樹脂を充填したカラムに連続的に流してもよく、
またイオン交換樹脂を充填したカラムを外部から
加熱してもよい。あるいは、イオン交換樹脂を別
の加熱容器に移し、水の存在下に撹拌して加熱す
ることもできる。 As described above, the strongly acidic cation exchange resin adsorbed with aziridine-2-carboxylic acid is heated in a wet state. The heating method is not particularly limited, but it is necessary to heat it in a wet state, that is, in the presence of water. For example, heated water may be continuously passed through a column filled with ion exchange resin,
Alternatively, the column filled with ion exchange resin may be heated from the outside. Alternatively, the ion exchange resin can be transferred to a separate heating container and heated while stirring in the presence of water.
アジリジン−２−カルボン酸を吸着させたイオ
ン交換樹脂を加熱する条件は40〜120℃、１〜100
時間、好ましくは50〜100℃、２〜50時間であ
る。反応は40℃以下の温度、例えば、室温でも進
行するが、反応の完結に著しく長時間を要し、実
際的ではない。 The conditions for heating the ion exchange resin adsorbed with aziridine-2-carboxylic acid are 40 to 120℃ and 1 to 100℃.
The time is preferably 50 to 100°C and 2 to 50 hours. Although the reaction proceeds at temperatures below 40° C., for example at room temperature, it takes an extremely long time to complete the reaction, which is not practical.
イオン交換樹脂に吸着状態のアジリジン−２−
カルボン酸を加熱して生成するDL−セリンはイ
オン交換樹脂に吸着された状態にある。このDL
−セリンを単離するには、常法にしたがつて、生
成したセリンをイオン交換樹脂から溶離例えば、
アンモニア水で吸着されているDL−セリンを溶
離し、その溶離液を濃縮乾固するか、または濃縮
後等電点晶析したりする方法で単離することがで
きる。 Aziridine-2- adsorbed on ion exchange resin
DL-serine, which is produced by heating carboxylic acid, is adsorbed on the ion exchange resin. This DL
- To isolate serine, the formed serine is eluted from an ion exchange resin according to conventional methods, e.g.
It can be isolated by eluting DL-serine adsorbed with aqueous ammonia and concentrating the eluate to dryness, or by performing isoelectric crystallization after concentration.
以下、実施例によつて本発明を説明する。 The present invention will be explained below with reference to Examples.
参考例 １
（アジリジン−２−カルボン酸リチウム塩の合
成）
100ｇのα−クロロ−β−アミノプロピオン酸
エチルエステルの塩酸塩を１の脱水エタノール
に溶かし、さらに200ｇのトリエタノールアミン
を添加したのち、撹拌下に60〜70℃で５時間反応
させ、析出したトリエタノールアミンの塩酸塩を
別、少量のエタノールで洗浄する。洗液を合
して冷却下に１規定の水酸化リチウム水溶液550
mlを徐々に加え、冷蔵庫中に24時間放置する。そ
の後反応液を減圧下に濃縮乾固し、得られた残留
物（シロツプ状物質）に200mlのベンゼンを添加
し、共沸蒸留によつて水を完全に除去する。つい
で400mlの熱エタノールを添加し、冷却すると沈
澱が析出する。800mlのエーテルを添加して結晶
を十分に沈澱、析出させてから、析出した沈澱を
別し、エーテルで洗浄することによつて、11.2
ｇのアジリジン−２−カルボン酸リチウム塩を得
た。融点261〜267℃（分解）。Reference Example 1 (Synthesis of aziridine-2-carboxylic acid lithium salt) 100 g of α-chloro-β-aminopropionic acid ethyl ester hydrochloride was dissolved in 1 dehydrated ethanol, and 200 g of triethanolamine was further added. The reaction is carried out at 60 to 70°C for 5 hours with stirring, and the precipitated triethanolamine hydrochloride is separated and washed with a small amount of ethanol. Combine the washing liquids and add 1N lithium hydroxide aqueous solution 550 while cooling.
Gradually add ml and leave in the refrigerator for 24 hours. Thereafter, the reaction solution is concentrated to dryness under reduced pressure, 200 ml of benzene is added to the resulting residue (syrup-like substance), and water is completely removed by azeotropic distillation. Then, 400 ml of hot ethanol is added, and upon cooling, a precipitate separates out. 11.2 by adding 800 ml of ether to sufficiently precipitate the crystals, separating the precipitate and washing with ether.
g of aziridine-2-carboxylic acid lithium salt was obtained. Melting point 261-267°C (decomposition).
参考例 ２
（アジリジン−２−カルボン酸ナトリウム塩の
合成）
α，β−ジブロムプロピオン酸イソプロピルエ
ステルと液安とから合成したアジリジン−２−カ
ルボン酸イソプロピルエステル20ｇを600mlの脱
水エーテルに溶かし、撹拌しながら冷却下に4.0
ｇのナトリウムをエタノール60mlに溶かした溶液
を徐々に滴下し、さらにエーテル550mlを添加す
る。ついで3.2ｇの水を滴下装入し、３時間室温
に放置する。析出した針状結晶を別し、真空下
に乾燥することによつて14.2ｇのアジリジン−２
−カルボン酸ナトリウムを得た。Reference Example 2 (Synthesis of aziridine-2-carboxylic acid sodium salt) 20 g of aziridine-2-carboxylic acid isopropyl ester synthesized from α,β-dibromopropionate isopropyl ester and liquid ammonium was dissolved in 600 ml of dehydrated ether and stirred. 4.0 while under cooling
A solution of 1 g of sodium dissolved in 60 ml of ethanol is gradually added dropwise, and then 550 ml of ether is added. Then, 3.2 g of water was added dropwise and left at room temperature for 3 hours. By separating the precipitated needle-like crystals and drying under vacuum, 14.2 g of aziridine-2 was obtained.
- Sodium carboxylate was obtained.
融点153〜156℃。 Melting point 153-156℃.
実施例 １
参考例１で合成したアジリジン−２−カルボン
酸リチウム塩9.2ｇを水200mlに溶解し、冷却下に
５％硫酸で中和した水溶液を強酸性型カチオン交
換樹脂Lewatit Ｓ−100（Ｈ型）（バイエル社製）
280mlを充填したカラムに通じ、さらに蒸留水300
mlで水洗してアジリジン−２−カルボン酸を吸着
させる。その後、該イオン交換樹脂を90〜95℃に
加熱された熱水を６時間循環させる。反応後、イ
オン交換樹脂カラムを冷却し、3Nのアンモニア
水500mlと蒸留水500mlで溶離し、溶離液を濃縮乾
固することによつて10.5ｇ（純度93.5％）のDL
−セリンを得た。Example 1 9.2 g of the aziridine-2-carboxylic acid lithium salt synthesized in Reference Example 1 was dissolved in 200 ml of water, and the aqueous solution was neutralized with 5% sulfuric acid while cooling. type) (manufactured by Bayer)
Passed through a column packed with 280 ml of distilled water and 300 ml of distilled water.
ml of water to adsorb aziridine-2-carboxylic acid. Thereafter, hot water heated to 90 to 95°C is circulated through the ion exchange resin for 6 hours. After the reaction, the ion exchange resin column was cooled, eluted with 500 ml of 3N ammonia water and 500 ml of distilled water, and the eluate was concentrated to dryness to obtain 10.5 g (purity 93.5%) of DL.
- Obtained serine.
DL−セリン収率93.5％／（対アジリジン−２
−カルボン酸リチウム）
実施例 ２
実施例１においてアジリジン−２−カルボン酸
リチウム塩のかわりに参考例２で合成したアジリ
ジン−２−カルボン酸ナトリウム10.9ｇを用い、
Lewatit Ｓ−100のかわりにLewatit SP−120
（Ｈ型）（バイエル社製）400mlを用いる他は実施
例１と同様に行うことによつて10.3ｇ（純度92.8
％）のDL−セリンを得た。 DL-serine yield 93.5%/(vs. aziridine-2
- lithium carboxylate) Example 2 In Example 1, 10.9 g of sodium aziridine-2-carboxylate synthesized in Reference Example 2 was used instead of the lithium salt of aziridine-2-carboxylate,
Lewatit SP-120 instead of Lewatit S-100
(H-type) (manufactured by Bayer) 10.3 g (purity 92.8) was obtained in the same manner as in Example 1 except that 400 ml of
%) of DL-serine was obtained.
実施例 ３
実施例１においてアジリジン−２−カルボン酸
を吸着したイオン交換樹脂を500mlのフラスコに
移し、該フラスコ中、90〜95℃で６時間反応させ
たのち、実施例１と同様にアンモニア水と水で溶
離することによつて10.5ｇ（純度93.2％）のDL
−セリンを得た。Example 3 The ion exchange resin that adsorbed aziridine-2-carboxylic acid in Example 1 was transferred to a 500 ml flask, and after reacting in the flask at 90 to 95°C for 6 hours, aqueous ammonia was added in the same manner as in Example 1. DL of 10.5 g (93.2% purity) by elution with water
- Obtained serine.
実施例 ４
実施例１においてアジリジン−２−カルボン酸
リチウムの水溶液をアルカリ性のまま吸着させる
他は実施例１と同様に行うことによつて10.4ｇ
（純度92.1％）のDL−セリンを得た。Example 4 10.4 g was prepared in the same manner as in Example 1, except that the aqueous solution of lithium aziridine-2-carboxylate was adsorbed in an alkaline state.
(purity 92.1%) DL-serine was obtained.
実施例 ５
アジリジン−２−カルボン酸リチウム塩9.2ｇ
を水200mlに溶解し、この水溶液を強酸性型カチ
オン交換樹脂Lewatit Ｓ−100（Ｈ型）（バイエル
社製）150mlを充填したカラムに通じ、さらに蒸
留水300mlを流してアジリジン−２−カルボン酸
を吸着させた。その後該イオン交換樹脂に80〜85
℃に加熱された温水を循環し、80〜85℃で８時間
循環させた。反応後、該イオン交換樹脂カラムを
冷却し3Nのアンモニア水250mlと蒸留水300mlで
溶離した。溶離液は減圧下に液量が約30ｇになる
まで濃縮したのち濃塩酸を添加してPHを5.6に調
整した。５℃に冷却し析出している結晶を取
し、少量の冷水で洗浄してから乾燥することによ
つて8.1ｇのDL−セリンの白色結晶を得た。高速
液体クロマトグラフイーでの純度分析の結果は純
度99.3％であつた。Example 5 Aziridine-2-carboxylic acid lithium salt 9.2g
was dissolved in 200 ml of water, and this aqueous solution was passed through a column packed with 150 ml of strongly acidic cation exchange resin Lewatit S-100 (H type) (manufactured by Bayer), and then 300 ml of distilled water was passed through to dissolve aziridine-2-carboxylic acid. was adsorbed. Then add 80 to 85% to the ion exchange resin.
Warm water heated to 0.degree. C. was circulated at 80-85.degree. C. for 8 hours. After the reaction, the ion exchange resin column was cooled and eluted with 250 ml of 3N ammonia water and 300 ml of distilled water. The eluate was concentrated under reduced pressure until the liquid amount was about 30 g, and then concentrated hydrochloric acid was added to adjust the pH to 5.6. The precipitated crystals were collected by cooling to 5° C., washed with a small amount of cold water, and then dried to obtain 8.1 g of white crystals of DL-serine. Purity analysis using high performance liquid chromatography showed a purity of 99.3%.
Claims (1)
オン交換樹脂に吸着させ、水の存在下に加熱する
ことを特徴とするDL−セリンの製造方法。1. A method for producing DL-serine, which comprises adsorbing aziridine-2-carboxylic acid onto a strongly acidic cation exchange resin and heating it in the presence of water.
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15925079A JPS5683454A (en) | 1979-12-10 | 1979-12-10 | Preparation of dl-serine |
| US06/212,102 US4304933A (en) | 1979-12-10 | 1980-12-02 | Production of DL-serine |
| EP19800304439 EP0030474B1 (en) | 1979-12-10 | 1980-12-09 | Process for the production of dl-serines |
| DE8080304440T DE3067054D1 (en) | 1979-12-10 | 1980-12-09 | Process for producing solutions of aziridine-2-carboxylic acid salts |
| MX10181780U MX7073E (en) | 1979-12-10 | 1980-12-09 | IMPROVED PROCEDURE FOR PRODUCING DL-SERINA |
| DE8080304439T DE3061695D1 (en) | 1979-12-10 | 1980-12-09 | Process for the production of dl-serines |
| EP80304440A EP0030475B1 (en) | 1979-12-10 | 1980-12-09 | Process for producing solutions of aziridine-2-carboxylic acid salts |
| CA000366383A CA1145359A (en) | 1979-12-10 | 1980-12-09 | Production of dl-serine |
| AU65263/80A AU542947B2 (en) | 1979-12-10 | 1980-12-10 | D-l serine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15925079A JPS5683454A (en) | 1979-12-10 | 1979-12-10 | Preparation of dl-serine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5683454A JPS5683454A (en) | 1981-07-08 |
| JPS6258347B2 true JPS6258347B2 (en) | 1987-12-05 |
Family
ID=15689630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15925079A Granted JPS5683454A (en) | 1979-12-10 | 1979-12-10 | Preparation of dl-serine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5683454A (en) |
-
1979
- 1979-12-10 JP JP15925079A patent/JPS5683454A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5683454A (en) | 1981-07-08 |
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