JPS6334857B2 - - Google Patents
Info
- Publication number
- JPS6334857B2 JPS6334857B2 JP13202880A JP13202880A JPS6334857B2 JP S6334857 B2 JPS6334857 B2 JP S6334857B2 JP 13202880 A JP13202880 A JP 13202880A JP 13202880 A JP13202880 A JP 13202880A JP S6334857 B2 JPS6334857 B2 JP S6334857B2
- Authority
- JP
- Japan
- Prior art keywords
- malic acid
- optically active
- ethylamine
- tolyl
- phenyl
- 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 38
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 34
- 235000011090 malic acid Nutrition 0.000 claims description 31
- 239000001630 malic acid Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 6
- ZICDZTXDTPZBKH-UHFFFAOYSA-N 2-(4-methylphenyl)-1-phenylethanamine Chemical compound C1=CC(C)=CC=C1CC(N)C1=CC=CC=C1 ZICDZTXDTPZBKH-UHFFFAOYSA-N 0.000 claims description 3
- 229940099690 malic acid Drugs 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000007864 aqueous solution Substances 0.000 description 16
- 239000013078 crystal Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229940116298 l- malic acid Drugs 0.000 description 5
- 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 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000003729 cation exchange resin Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- VKJXAQYPOTYDLO-UHFFFAOYSA-N 4-methylphenethylamine Chemical compound CC1=CC=C(CCN)C=C1 VKJXAQYPOTYDLO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- BJEPYKJPYRNKOW-UWTATZPHSA-N (R)-malic acid Chemical compound OC(=O)[C@H](O)CC(O)=O BJEPYKJPYRNKOW-UWTATZPHSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000001362 calcium malate Substances 0.000 description 2
- OLOZVPHKXALCRI-UHFFFAOYSA-L calcium malate Chemical compound [Ca+2].[O-]C(=O)C(O)CC([O-])=O OLOZVPHKXALCRI-UHFFFAOYSA-L 0.000 description 2
- 229940016114 calcium malate Drugs 0.000 description 2
- 235000011038 calcium malates Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- WPUMTJGUQUYPIV-JIZZDEOASA-L disodium (S)-malate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](O)CC([O-])=O WPUMTJGUQUYPIV-JIZZDEOASA-L 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 235000013373 food additive Nutrition 0.000 description 2
- 239000002778 food additive Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 235000019265 sodium DL-malate Nutrition 0.000 description 2
- 239000001394 sodium malate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 238000009835 boiling Methods 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
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001415 potassium malate Substances 0.000 description 1
- 235000011033 potassium malate Nutrition 0.000 description 1
- SVICABYXKQIXBM-UHFFFAOYSA-L potassium malate Chemical compound [K+].[K+].[O-]C(=O)C(O)CC([O-])=O SVICABYXKQIXBM-UHFFFAOYSA-L 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000005671 trienes Chemical class 0.000 description 1
Description
【発明の詳細な説明】
本発明は光学活性なリンゴ酸の製造方法に関
し、更に詳しくは、DL―リンゴ酸に、光学活性
なｄ―またはｌ―α―フエニル―β―（ｐ―トリ
ル）エチルアミンを反応させて光学活性なジアス
テレオアイソマー塩を生成せしめ、次いでこれを
分解することを特徴とする光学活性なリンゴ酸を
製造する方法であつて、その目的とするところ
は、食品添加物、医薬品等として重要な光学活性
なリンゴ酸を安価にして工業的に有利に製造する
ことにある。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing optically active malic acid, and more particularly, to a method for producing optically active malic acid, optically active d- or l-α-phenyl-β-(p-tolyl)ethylamine is added to DL-malic acid. A method for producing optically active malic acid, which is characterized by reacting to produce an optically active diastereoisomeric salt, and then decomposing the salt, and the purpose is to produce an optically active malic acid as a food additive, a pharmaceutical product, etc. The purpose of the present invention is to produce optically active malic acid, which is important as a chemical, at a low cost and advantageously industrially.
従来からリンゴ酸は、食品添加物としてDL―
体で使用されている。しかし、乳児にはＤ体を代
謝する能力がなく、成人にとつてもＤ体は無害で
はあるが、不必要な物質であるので摂取しないほ
うが望ましいという観点からするとDL―体から
光学活性なＬ―リンゴ酸を得ることは重要であ
る。また、とくにＬ―リンゴ酸は、アミノ酸輸
液、各種ドリンク剤等の医薬用としての重要な用
途がある。 Malic acid has traditionally been DL- as a food additive.
used in the body. However, infants do not have the ability to metabolize D-form, and although D-form is harmless to adults, it is an unnecessary substance and it is better not to ingest it. - Obtaining malic acid is important. In addition, L-malic acid in particular has important medicinal uses such as amino acid infusions and various drinks.
このような光学活性なリンゴ酸を製造する方法
としては、従来、DL―リンゴ酸にシンコニン
〔Pharm.Weekblad85，435〜７（1950）〕、α―フ
エニルエチルアミン〔J.Am.Chem.soc.47，1168
―73（1925）〕、あるいは、Ｌ―ヒスチジン等のア
ミノ酸〔特開昭52−77011〕を作用させて光学分
割する方法、発酵法〔たとえば特開昭51−
130587〕あるいは、フマール酸を原料とする酵素
法〔たとえば特開昭51−70880〕等が知られてい
る。 Conventionally, methods for producing optically active malic acid include DL-malic acid, cinchonine [Pharm.Weekblad 85 , 435-7 (1950)], and α-phenylethylamine [J.Am.Chem.soc .47 , 1168
-73 (1925)], or a method of optical resolution using an amino acid such as L-histidine [JP-A-52-77011], or a fermentation method [e.g., JP-A-51-77011].
130587] or an enzymatic method using fumaric acid as a raw material [for example, JP-A-51-70880], etc. are known.
しかるに、光学分割法については、高価な分割
剤を使用していることまた分割剤の回収が困難で
あるという欠点がある。さらに発酵法や酵素法に
ついては、製造工程が繁雑でコストが高いという
欠点があり、これらの方法はいずれも工業的に有
利な製法とはいえなかつた。 However, the optical resolution method has disadvantages in that it uses an expensive resolving agent and that it is difficult to recover the resolving agent. Furthermore, fermentation methods and enzyme methods have the drawbacks of complicated manufacturing processes and high costs, and neither of these methods can be considered to be industrially advantageous manufacturing methods.
このようなことから、本発明者らは安価にしか
も工業的有利に光学活性なリンゴ酸を製造すべく
鋭意検討の結果、DL―リンゴ酸にα―フエニル
―β―（ｐ―トリル）エチルアミンの光学活性体
を反応させて光学活性なジアステレオアイソマー
塩を生成せしめ、次いでこれを分解することによ
り、上記目的が容易に達成させられることを見出
し、本発明に至つた。 For these reasons, the present inventors have conducted intensive studies to produce optically active malic acid at low cost and with industrial advantage. The inventors have discovered that the above object can be easily achieved by reacting optically active substances to produce optically active diastereoisomeric salts, and then decomposing them, leading to the present invention.
以下、本発明について説明する。 The present invention will be explained below.
DL―リンゴ酸と光学活性なα―フエニル―β
―（ｐ―トリル）エチルアミンは、まず有機溶媒
中で反応させてジアステレオアイソマー塩を生成
せしめるが、この反応における両者のモル比は通
常DL―リンゴ酸１モルあたり光学活性なα―フ
エニル―β―（ｐ―トリル）エチルアミンが約
0.5〜２モル、好ましくは１〜1.8モルである。 DL-malic acid and optically active α-phenyl-β
-(p-Tolyl)ethylamine is first reacted in an organic solvent to form a diastereoisomer salt, but the molar ratio of both in this reaction is usually DL-malic acid per mole of optically active α-phenyl-β. -(p-tolyl)ethylamine is approx.
The amount is 0.5 to 2 mol, preferably 1 to 1.8 mol.
上記反応で使用される有機溶媒としてはメタノ
ール、エタノール、イソプロパノール、アセトン
等およびそれらの水溶液、あるいは酢酸エチル、
クロロホルム、トルエンおよびそれらの混合溶媒
等が用いられる。 Organic solvents used in the above reaction include methanol, ethanol, isopropanol, acetone, etc. and their aqueous solutions, or ethyl acetate,
Chloroform, toluene, a mixed solvent thereof, etc. are used.
反応温度は、−20℃から使用される溶媒の沸点
の範囲で任意であるが、好ましくはジアステレオ
アイソマー塩が析出する温度以上である。 The reaction temperature is arbitrary within the range from -20°C to the boiling point of the solvent used, but is preferably at least the temperature at which the diastereoisomer salt precipitates.
上記反応によつてジアステレオアイソマー塩を
生成せしめたのち、反応混合物を徐冷し、光学活
性体の一方のジアステレオアイソマー塩を析出さ
せる。このとき、該塩が析出するまえに、これと
同種の種晶を混合系に接種することがより好まし
い。 After the diastereoisomer salt is produced by the above reaction, the reaction mixture is slowly cooled to precipitate one diastereoisomer salt of the optically active substance. At this time, it is more preferable to inoculate the mixed system with seed crystals of the same type as the salt before it precipitates.
析出した塩をろ別し、乾燥したのちアルカリ水
溶液によつて該塩を分解し、分解液について有機
溶媒（たとえば、トルエン、クロロホルム、エー
テル、ベンゼンなど）で抽出処理を行ない、分割
剤として使用した光学活性なα―フエニル―β―
（ｐ―トリル）エチルアミンを有機層として高収
率で回収し、光学活性なリンゴ酸を含んだアルカ
リ水溶液を得る。 The precipitated salt was filtered, dried, and then decomposed with an aqueous alkaline solution. The decomposed solution was extracted with an organic solvent (e.g., toluene, chloroform, ether, benzene, etc.) and used as a resolving agent. Optically active α-phenyl-β-
(p-Tolyl)ethylamine is recovered as an organic layer in high yield to obtain an alkaline aqueous solution containing optically active malic acid.
ここで使用されるアルカリは、水酸化ナトリウ
ム、水酸化カリウム、炭酸ナトリウム、炭酸カリ
ウム等であり、その量は、ろ別した結晶に対して
２モル倍以上任意であるが、通常２〜2.4モルで
分解するのが好ましい。 The alkali used here is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, etc., and the amount is arbitrary at least 2 times the amount of the filtered crystals, but usually 2 to 2.4 mol. It is preferable to decompose with
得られた光学活性なリンゴ酸のアルカリ水溶液
は常法によつて、例えば陽イオン交換樹脂（強酸
性）を通して、光学活性なリンゴ酸水溶液とし、
水を留去することにより、光学活性なリンゴ酸を
得ることができるし、或いは得られた光学活性な
リンゴ酸のアルカリ水溶液に濃塩酸を加えてリン
ゴ酸を遊離させたのち、水酸化カルシウムの如き
カルシウム塩を加えることによりリンゴ酸のカル
シウム塩を単離し、これを常法により酸分解して
光学活性なリンゴ酸を得ることができる。尚、分
割剤として用いた光学活性なα―フエニル―β―
（ｐ―トリル）エチルアミンは、上述したように
高収率で回収することができる。このことは工業
的に実施するうえでの大きな利点である。また析
出したジアステレオアイソマー塩をろ別したろ液
からも適切な処理を行なうことによつて、同様に
分割剤のアミンを回収することができると同時
に、光学純度は良くないが、もう一方の光学活性
なリンゴ酸が回収される。 The obtained alkaline aqueous solution of optically active malic acid is converted into an optically active aqueous solution of malic acid by a conventional method, for example, through a cation exchange resin (strongly acidic).
Optically active malic acid can be obtained by distilling off water, or by adding concentrated hydrochloric acid to the obtained alkaline aqueous solution of optically active malic acid to liberate malic acid. By adding such a calcium salt, the calcium salt of malic acid can be isolated, and this can be acid-decomposed by a conventional method to obtain optically active malic acid. In addition, the optically active α-phenyl-β- used as a resolving agent.
(p-Tolyl)ethylamine can be recovered in high yield as described above. This is a great advantage in industrial implementation. In addition, by performing appropriate treatment from the filtrate obtained by filtering off the precipitated diastereoisomer salt, it is possible to similarly recover the amine, which is the resolving agent, and at the same time, the other amine can be recovered, although the optical purity is not good. Optically active malic acid is recovered.
以下実施例によつて本発明を具体的に説明す
る。 The present invention will be specifically explained below using Examples.
実施例 １
DL―リンゴ酸134.1ｇ（１モル）、メタノール
1080ｇおよび水720ｇをフラスコに仕込み、還流
温度（75〜６℃）で保温する。これにｄ―α―フ
エニル―β―（ｐ―トリル）エチルアミン295.8
ｇ（1.4モル）を適下する。その後74〜５℃で別
途に調整したＬ―リンゴ酸とｄ―α―フエニル―
β―（ｐ―トリル）エチルアミンのジアステレオ
アイソマー塩の結晶を種晶として少量加え、20℃
まで徐冷し、析出した結晶をろ別する。ろ別後乾
燥した結晶に水１および水酸化ナトリウム25％
水溶液140ｇを加え、30分間45〜50で撹拌する。
その後、トルエン200ｇでｄ―α―フエニル―β
―（ｐ―トリル）エチルアミンを抽出分離し、リ
ンゴ酸ナトリウムの水溶液を得る。Example 1 DL-malic acid 134.1g (1 mol), methanol
1080 g and 720 g of water are charged into a flask and kept at reflux temperature (75-6°C). To this, d-α-phenyl-β-(p-tolyl)ethylamine 295.8
g (1.4 mol). After that, separately prepared L-malic acid and d-α-phenyl-
Add a small amount of diastereoisomer salt crystals of β-(p-tolyl)ethylamine as a seed crystal, and
The precipitated crystals are filtered off. After filtering, add 1 part water and 25% sodium hydroxide to the dried crystals.
Add 140 g of aqueous solution and stir at 45-50 for 30 minutes.
After that, d-α-phenyl-β was added with 200 g of toluene.
-(p-Tolyl)ethylamine is extracted and separated to obtain an aqueous solution of sodium malate.
この水溶液を陽イオン交換樹脂で処理し、リン
ゴ酸水溶液を得る。さらに水を留去し、乾燥して
Ｌ―リンゴ酸54.0ｇ〔分割収率80.5％、〔α〕20 D＝
−10.9゜（Ｃ＝２，1N NaOH）光学純度99.1％〕
を得る。 This aqueous solution is treated with a cation exchange resin to obtain a malic acid aqueous solution. Further, water was distilled off and dried to obtain 54.0 g of L-malic acid [resolution yield 80.5%, [α] 20 D =
-10.9゜(C=2,1N NaOH) Optical purity 99.1%]
get.
実施例 ２
DL―リンゴ酸134.1ｇ（１モル）、メタノール
1080ｇおよび水720ｇをフラスコに仕込み、還流
温度（75〜76℃）で保温する。これにｌ―α―フ
エニル―β―（ｐ―トリル）エチルアミン295.8
ｇ（1.4モル）を滴下する。その後74〜５℃で別
途に調整したＤ―リンゴ酸とｌ―α―フエニル―
β―（ｐ―トリル）エチルアミンのジアステレオ
アイソマー塩の結晶を種晶として少量加え、20℃
まで徐冷し、析出した結晶をろ別する。ろ別後乾
燥した結晶に水１および水酸化カリウム25％水
溶液200ｇを加え、30分間45〜50℃で撹拌する。
その後、ベンゼン200ｇでｌ―α―フエニル―β
―（ｐ―トリル）エチルアミンを抽出分離し、リ
ンゴ酸カリウムの水溶液を得る。Example 2 DL-malic acid 134.1g (1 mol), methanol
1080 g and 720 g of water are charged into a flask and kept at reflux temperature (75-76°C). To this, l-α-phenyl-β-(p-tolyl)ethylamine 295.8
g (1.4 mol) was added dropwise. After that, D-malic acid and l-α-phenyl- were separately prepared at 74-5℃.
Add a small amount of diastereoisomer salt crystals of β-(p-tolyl)ethylamine as a seed crystal, and
The precipitated crystals are filtered off. After filtration, 1 part of water and 200 g of a 25% potassium hydroxide aqueous solution are added to the dried crystals, and the mixture is stirred at 45-50°C for 30 minutes.
Then, with 200g of benzene, l-α-phenyl-β
-(p-Tolyl)ethylamine is extracted and separated to obtain an aqueous solution of potassium malate.
この水溶液を陽イオン交換樹脂で処理し、リン
ゴ酸水溶液を得る。さらに水を留去し、乾燥して
Ｄ―リンゴ酸53.5ｇ〔分割収率79.8％、〔α〕20 D＝
＋10.8（Ｃ＝２、1N NaOH）、光学純度98.2％〕
を得る。 This aqueous solution is treated with a cation exchange resin to obtain a malic acid aqueous solution. Further, water was distilled off and dried to give 53.5 g of D-malic acid [separation yield 79.8%, [α] 20 D =
+10.8 (C=2, 1N NaOH), optical purity 98.2%]
get.
実施例 ３
DL―リンゴ酸134.1ｇ（１モル）、イソプロパ
ノール1600ｇおよび水400ｇをフラスコに仕込み、
還流温度（83〜４℃）で保温する。これにｄ―α
―フエニル―β―（ｐ―トリル）エチルアミン
295.8ｇ（1.4モル）を滴下する。その後82〜３℃
で別途に調整したＬ―リンゴ酸とｄ―α―フエニ
ル―β―（ｐ―トリル）エチルアミンのジアステ
レオアイソマー塩の結晶を種晶として少量加え、
30℃まで徐冷し、析出した結晶をろ別する。ろ別
後乾燥した結晶に水500ｇおよび水酸化ナトリウ
ムの25％水溶液140ｇを加え、30分間45〜50℃で
撹拌する。その後、トリエン200ｇでｄ―α―フ
エニル―β―（ｐ―トリル）エチルアミンを抽出
分離し、リンゴ酸ナトリウムの水溶液を得る。Example 3 DL-malic acid 134.1g (1 mol), isopropanol 1600g and water 400g were charged in a flask,
Keep warm at reflux temperature (83-4°C). To this d-α
-Phenyl-β-(p-tolyl)ethylamine
Add 295.8 g (1.4 mol) dropwise. Then 82~3℃
Add a small amount of diastereoisomer salt crystals of L-malic acid and d-α-phenyl-β-(p-tolyl)ethylamine prepared separately as seed crystals,
Cool slowly to 30°C and filter out precipitated crystals. After filtration, 500 g of water and 140 g of a 25% aqueous solution of sodium hydroxide are added to the dried crystals and stirred for 30 minutes at 45-50°C. Thereafter, d-α-phenyl-β-(p-tolyl)ethylamine is extracted and separated using 200 g of triene to obtain an aqueous solution of sodium malate.
これに濃塩酸96ｇを加え、遊離リンゴ酸を形成
させ、そこへ水酸化カルシウム70ｇを加えて中和
し、析出するリンゴ酸カルシウムをろ別する。 Add 96 g of concentrated hydrochloric acid to form free malic acid, neutralize it by adding 70 g of calcium hydroxide, and filter out the precipitated calcium malate.
得られたリンゴ酸カルシウム（２水和物：79.9
ｇ）に2N硫酸400mlを加え、沈殿する硫酸カルシ
ウムをろ別する。ろ液は、強酸性陽イオン交換樹
脂及び弱塩基性陰イオン交換樹脂を通して、Ｌ―
リンゴ酸水溶液を得る。さらに水を留去し、乾燥
してＬ―リンゴ酸48.3ｇ〔分割収率72.0％〔α〕20 D
＝−10.6（Ｃ＝２、1N NaOH）、光学純度96.4％〕
を得る。 Obtained calcium malate (dihydrate: 79.9
Add 400 ml of 2N sulfuric acid to g) and filter off precipitated calcium sulfate. The filtrate is passed through a strongly acidic cation exchange resin and a weakly basic anion exchange resin to L-
Obtain a malic acid aqueous solution. Further, water was distilled off and dried to obtain 48.3 g of L-malic acid [split yield 72.0% [α] 20 D
=-10.6 (C=2, 1N NaOH), optical purity 96.4%]
get.
Claims (1)
α―フエニル―β―（ｐ―トリル）エチルアミン
を反応させて光学活性なジアステレオアイソマー
塩を生成せしめ、次いでこれを分解することを特
徴とする光学活性なリンゴ酸の製造方法。1 DL - d- or l- optically active to malic acid
A method for producing optically active malic acid, which comprises reacting α-phenyl-β-(p-tolyl)ethylamine to produce an optically active diastereoisomer salt, and then decomposing the salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13202880A JPS5756439A (en) | 1980-09-22 | 1980-09-22 | Preparation of optically active malic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13202880A JPS5756439A (en) | 1980-09-22 | 1980-09-22 | Preparation of optically active malic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5756439A JPS5756439A (en) | 1982-04-05 |
| JPS6334857B2 true JPS6334857B2 (en) | 1988-07-12 |
Family
ID=15071805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13202880A Granted JPS5756439A (en) | 1980-09-22 | 1980-09-22 | Preparation of optically active malic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5756439A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3247981A1 (en) * | 1982-12-24 | 1984-06-28 | Degussa Ag, 6000 Frankfurt | METHOD FOR OBTAINING L-APPLE ACID |
| DE3920745A1 (en) * | 1989-06-24 | 1991-01-03 | Bayer Ag | RUBBER COMPOSITIONS CONTAINING SULFUR MODIFIED POLYCHLOROPRENE GEL |
-
1980
- 1980-09-22 JP JP13202880A patent/JPS5756439A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5756439A (en) | 1982-04-05 |
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