JPH024581B2 - - Google Patents
Info
- Publication number
- JPH024581B2 JPH024581B2 JP54102261A JP10226179A JPH024581B2 JP H024581 B2 JPH024581 B2 JP H024581B2 JP 54102261 A JP54102261 A JP 54102261A JP 10226179 A JP10226179 A JP 10226179A JP H024581 B2 JPH024581 B2 JP H024581B2
- Authority
- JP
- Japan
- Prior art keywords
- phenylethylamine
- optically active
- mandelic acid
- acid
- yield
- 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 - Lifetime
Links
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 claims description 61
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 28
- 230000003287 optical effect Effects 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 13
- 229960002510 mandelic acid Drugs 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- -1 hydrochloric acid Chemical class 0.000 description 6
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 3
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 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
- 238000005516 engineering process Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、（±）―１―フエニルエチルアミン
の光学分割して光学活性な１―フエニルエチルア
ミンを製造する方法に関する。
The present invention relates to a method for producing optically active 1-phenylethylamine by optically resolving (±)-1-phenylethylamine.
光学活性１―フエニルエチルアミンは、エフエ
ドリン、キニーネまたはブルシン等の塩基性天然
光学分割剤と同様に、ラセミ酸の光学分割剤とし
て広く利用されているばかりでなく、不斉合成に
おける不斉源として注目されている。そのため、
（±）―１―フエニルエチルアミンの簡単な光学
分割法の出現が望まれている。
従来、（±）―１―フエニルエチルアミンの光
学活性体を得る光学分割法として、（±）―酒石
酸および（−）―リンゴ酸を用いる方法〔A.W.
Ingersoll，Organic，Synthesis，Coll.Vol.2，
p506（1943）および日本化学会編、実験化学講座
18、有機化合物の反応（上）p539（1957）〕が
報告されているが、これらの方法はその操作が繁
雑で、比較的多量の溶媒が必要であり、その上何
回もの再結晶を行なわねばならないという欠点を
有していた。
本発明者らは、光学活性な１―フエニルエチル
アミンの重要性にかんがみ、その光学分割法につ
いて種々検討を重ねた結果、少量の水を媒体とし
て用い、その中で光学活性なマンデル酸を作用さ
せれば、（±）―１―フエニルエチルアミンを高
純度と高収率をもつて光学分割できること、およ
びその際に溶解性の（±）―１―フエニルエチル
アミン塩を共存させるのが有利であることを見出
した。
Optically active 1-phenylethylamine, like basic natural optical resolving agents such as efuedrin, quinine, or brucine, is not only widely used as an optical resolving agent for racemic acids, but also as an asymmetric source in asymmetric synthesis. Attention has been paid. Therefore,
It is desired that a simple optical resolution method for (±)-1-phenylethylamine be developed. Conventionally, as an optical resolution method to obtain an optically active form of (±)-1-phenylethylamine, a method using (±)-tartaric acid and (-)-malic acid [AW
Ingersoll, Organic, Synthesis, Coll.Vol.2,
p506 (1943) and edited by the Chemical Society of Japan, Experimental Chemistry Course
18, Reactions of Organic Compounds (Part 1) p. 539 (1957)], but these methods are complicated, require a relatively large amount of solvent, and require multiple recrystallizations. It had the disadvantage that it was necessary. In view of the importance of optically active 1-phenylethylamine, the present inventors conducted various studies on optical resolution methods, and as a result, using a small amount of water as a medium, optically active mandelic acid was It is advantageous to be able to optically resolve (±)-1-phenylethylamine with high purity and high yield by allowing soluble (±)-1-phenylethylamine salt to coexist at this time. I found that.
本発明の目的は、上記の知見を活かして、（±）
―１―フエニルエチルアミンの工業的に有利に光
学分割し、光学活性な１―フエニルエチルアミン
を製造する方法を提供することにある。
The purpose of the present invention is to take advantage of the above knowledge, (±)
An object of the present invention is to provide a method for industrially advantageous optical resolution of 1-phenylethylamine to produce optically active 1-phenylethylamine.
本発明の光学活性１―フエニルエチルアミンの
製造方法は、（±）―１―フエニルエチルアミン
を光学分割して光学活性１―フエニルエチルアミ
ンを製造する方法において、媒体中で（±）―１
―フエニルエチルアミンに対し光学活性なマンデ
ル酸を作用させ、生成したジアステレオマー塩の
溶解度差を利用して光学分割を行なうことからな
り、媒体として、ジアステレオマー混合物中に存
在する難溶性１―フエニルエチルアミン・マンデ
ル酸塩に対し等量ないし２倍量の水を使用し、か
つ溶解性（±）―１―フエニルエチルアミン塩を
共存させることを特徴とする。
本発明では、分割剤として用いるマンデル酸の
使用量を（±）―１―フエニルエチルアミンに対
して0.5〜１当量とすることが、１―フエニルエ
チルアミンを高純度、高収率で分割する上で好ま
しい。また、溶解性（±）―１―フエニルエチル
アミン塩の使用量は、光学活性マンデル酸に対し
てほぼ等モルとするのが適当である。
The method for producing optically active 1-phenylethylamine of the present invention is a method for producing optically active 1-phenylethylamine by optically resolving (±)-1-phenylethylamine in a medium.
- optically active mandelic acid is applied to phenylethylamine, and optical resolution is carried out by utilizing the difference in solubility of the resulting diastereomer salts. - It is characterized by using an equal to twice the amount of water for phenylethylamine mandelate, and coexisting with soluble (±) -1-phenylethylamine salt. In the present invention, the amount of mandelic acid used as a resolving agent is 0.5 to 1 equivalent to (±)-1-phenylethylamine to resolve 1-phenylethylamine with high purity and high yield. preferred above. Further, it is appropriate that the amount of the soluble (±)-1-phenylethylamine salt used be approximately equimolar to the optically active mandelic acid.
溶媒としては水を用いるのは、得られる光学活
性１―フエニルエチルアミンの純度、収率の点か
らも、経済性の点からも最適だからである。溶媒
量は比較的少量が好ましく、ジアステレオマー混
合物中に存在する難溶性１―フエニルエチルアミ
ン・マンデル酸塩の理論量に対して、等量ないし
２倍量の範囲からえらぶ。
共存させる溶解性（±）―１―フエニルエチル
アミン塩としては、（±）―１―フエニルエチル
アミンの酢酸塩、塩酸塩、硫酸塩、リン酸塩等が
適当である。これらは、（±）―１―フエニルエ
チルアミンと光学活性マンデル酸を含む水溶液に
酢酸、塩酸、硫酸、リン酸などの酸を添加するこ
とによつて、その場で形成できる。使用する酸の
量は、光学活性マンデル酸の量と合計して、（±）
―１―フエニルエチルアミンとほぼ等量とするこ
とが好ましい。たとえば、（±）―１―フエニル
エチルアミンに対し、光学活性マンデル酸を0.4
〜0.6当量、酢酸、塩酸、硫酸、リン酸などの酸
を0.6〜0.4当量、合わせてほぼ１当量である。
このようにして溶解性塩を共存させることによ
り、１―フエニルエチルアミンの一方の対掌体が
光学活性マンデル酸と難溶性塩を形成し、他方の
対掌体がこられ光学活性のない酸類と易溶性塩を
形成し、後記する実例が示すように、光学純度の
高い難溶性塩をより高い収率で取得することがで
きる。
本発明は、代表的には次の工程に従つて実施す
る。
イ （±）―１―フエニルエチルアミンを水に混
じ、これに（−）または（＋）―マンデル酸
0.4〜0.6当量および塩酸などの上記した溶解性
（±）―１―フエニルエチルアミン塩を形成す
る酸0.6〜0.4当量を加え、全体をほぼ中性とす
る。
ロ 加熱溶解して過飽和溶液とし、（＋）―１―
フエニルエチルアミン・（−）―マンデル酸塩
または（−）―１―フエチルアミン・（＋）―
マンデル酸塩を少量接種した後、徐冷して析出
した同種の活性体塩を分離する。
ハ 得られた塩を塩基で処理し、（＋）または
（−）―１―フエニルエチルアミンを得る。
ニ さらに酸を作用させて、（−）または（＋）
―マンデル酸を回収する。
The reason why water is used as a solvent is because it is optimal in terms of the purity and yield of the optically active 1-phenylethylamine obtained, as well as in terms of economic efficiency. The amount of solvent is preferably a relatively small amount, and is selected from a range of equivalent to twice the theoretical amount of poorly soluble 1-phenylethylamine mandelate present in the diastereomer mixture. As the soluble (±)-1-phenylethylamine salt to be allowed to coexist, acetate, hydrochloride, sulfate, phosphate, etc. of (±)-1-phenylethylamine are suitable. These can be formed in situ by adding an acid such as acetic acid, hydrochloric acid, sulfuric acid, or phosphoric acid to an aqueous solution containing (±)-1-phenylethylamine and optically active mandelic acid. The amount of acid used, combined with the amount of optically active mandelic acid, is (±)
It is preferable that the amount is approximately equal to that of -1-phenylethylamine. For example, 0.4% of optically active mandelic acid is added to (±)-1-phenylethylamine.
~0.6 equivalent, 0.6 to 0.4 equivalent of acids such as acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, etc., totaling approximately 1 equivalent. By coexisting soluble salts in this way, one enantiomer of 1-phenylethylamine forms a poorly soluble salt with optically active mandelic acid, and the other enantiomer forms an optically inactive acid. As shown in the example below, a poorly soluble salt with high optical purity can be obtained in a higher yield. The present invention is typically carried out according to the following steps. B. Mix (±)-1-phenylethylamine with water and add (-)- or (+)-mandelic acid.
Add 0.4 to 0.6 equivalents and 0.6 to 0.4 equivalents of an acid forming the above-mentioned soluble (±)-1-phenylethylamine salt, such as hydrochloric acid, to make the whole approximately neutral. (b) Heat and dissolve to make a supersaturated solution, (+)-1-
Phenylethylamine (-)-mandelate or (-)-1-phethylamine (+)-
After inoculating a small amount of mandelic acid salt, it is slowly cooled and the precipitated active salt of the same type is separated. C. Treat the obtained salt with a base to obtain (+) or (-)-1-phenylethylamine. (d) Further acid is applied to (-) or (+)
-Recover mandelic acid.
【参考例 １】
（±）―１―フエニルエチルアミン24.4ｇ
（0.2mol）を水30mlに加え、これに（＋）―マン
デル酸19.78ｇ（0.13mol）を加えて加熱溶解し
た。70℃まで徐冷し、（−）―１―フエニルエチ
ルアミン・（＋）―マンデル酸塩の種を250mg接種
し、３℃に冷却した後、析出した結晶を濾別し、
23.3ｇの（−）―フエニルエチルアミン・（＋）
―マンデル酸塩を得た。用いた（±）―１―フエ
ニルエチルアミン中の（−）―１―フエニルエチ
ルアミンに対しての収率は84.7％。
光学純度95.6％
〔α〕21 435＝＋108.6゜（Ｃ＝１，99％EtOH）
これに水40mlおよび水酸化ナトリウム4.0ｇ
（0.1mol）を加え、ベンゼン抽出した後、ベンゼ
ン層を減圧下で蒸留することにより（−）―フエ
ニルエチルアミン8.9ｇを得た。
収率73.0％
光学純度95.5％
〔α〕25 D＝−38.49゜（無溶媒）
ベンゼン抽出の際の水層と（−）―１―フエニ
ルエチルアミン・（＋）―マンデル酸塩を取得し
た母液とを合わせ、これに濃塩酸25ml
（0.24mol）を加え、３℃に冷却した後、析出し
た結晶を濾別し、11.65ｇの（＋）―マンデル酸
を回収した。
回収率58.9％[Reference example 1] (±)-1-phenylethylamine 24.4g
(0.2 mol) was added to 30 ml of water, and 19.78 g (0.13 mol) of (+)-mandelic acid was added thereto and dissolved by heating. It was slowly cooled to 70°C, inoculated with 250 mg of (-)-1-phenylethylamine/(+)-mandelate seeds, cooled to 3°C, and the precipitated crystals were filtered out.
23.3g of (-)-phenylethylamine (+)
- Obtained mandelate. The yield based on (-)-1-phenylethylamine in the (±)-1-phenylethylamine used was 84.7%. Optical purity 95.6% [α] 21 435 = +108.6° (C = 1,99% EtOH) To this, 40 ml of water and 4.0 g of sodium hydroxide
(0.1 mol) was added and extracted with benzene, and the benzene layer was distilled under reduced pressure to obtain 8.9 g of (-)-phenylethylamine. Yield 73.0% Optical purity 95.5% [α] 25 D = -38.49° (no solvent) Aqueous layer during benzene extraction and mother liquor from which (-)-1-phenylethylamine/(+)-mandelate was obtained Combine this with 25ml of concentrated hydrochloric acid.
(0.24 mol) was added, and after cooling to 3°C, the precipitated crystals were filtered off, and 11.65 g of (+)-mandelic acid was recovered. Recovery rate 58.9%
【参考例 ２】
（±）―１―フエニルエチルアミン100ｇ
（0.83mol）と、（＋）―マンデル酸81.8ｇ
（0.54mol）を水124mlに加え、加熱溶解した。こ
れを70℃まで徐冷し、（−）―１―フエニルエチ
ルアミン・（＋）―マンデル酸の種結晶を1.0ｇ接
種し、３℃に冷却した後、析出した結晶を濾別
し、95.0ｇ（0.35mol）の（−）―１―フエニル
エチルアミン・（＋）―マンデル酸塩を得た。
収率84.3％
これに水20mlおよび濃塩酸43.3ml（0.42mol）
を加え、加熱反応させたのち５℃に冷却して、
（＋）―マンデル酸24.3ｇを回収した。
回収率29.7％
この母液に25％NaOH水溶液113ml（0.71mol）
を加えてベンゼン抽出した後、ベンゼン層を減圧
下で蒸留することにより、（−）―１―フエニル
エチルアミン35.9ｇを得た。
収率71.8％
光学純度94.5％
〔α〕23 D＝−38.08゜（無溶媒）[Reference example 2] (±)-1-phenylethylamine 100g
(0.83mol) and (+)-mandelic acid 81.8g
(0.54 mol) was added to 124 ml of water and dissolved by heating. This was slowly cooled to 70℃, seed crystals of 1.0g of (-)-1-phenylethylamine/(+)-mandelic acid were inoculated, and after cooling to 3℃, the precipitated crystals were separated by filtration. g (0.35 mol) of (-)-1-phenylethylamine/(+)-mandelate was obtained. Yield 84.3% Add to this 20 ml of water and 43.3 ml (0.42 mol) of concentrated hydrochloric acid.
was added, heated to react, and then cooled to 5°C.
24.3 g of (+)-mandelic acid was recovered. Recovery rate: 29.7% 113ml (0.71mol) of 25% NaOH aqueous solution is added to this mother liquor.
After benzene extraction, the benzene layer was distilled under reduced pressure to obtain 35.9 g of (-)-1-phenylethylamine. Yield 71.8% Optical purity 94.5% [α] 23 D = -38.08° (no solvent)
【参考例 ３】
（±）―１―フエニルエチルアミン80.0ｇ
（0.66mmol）を水100mlに加え、これに（−）―
マンデル酸65.5ｇ（0.43mol）を加えて加熱溶解
した。70℃まで徐冷し、（＋）―１―フエニルエ
チルアミン・（−）―マンデル酸塩の種を1.0ｇ接
種し、３℃に冷却した後、析出した結晶を濾別
し、75.5ｇ（0.28mol）の（＋）―１―フエニル
エチルアミン・（−）―マンデル酸塩を得た。
収率83.7％
光学純度96.3％
〔α〕25 435＝−108.5゜（Ｃ＝１，99％EtOH）
これに水100mlおよび水酸化ナトリウム13.6ｇ
（0.34mol）を加え、ベンゼン抽出した後、ベン
ゼン層を減圧下で蒸留することにより、（＋）―
１―フエニルエチルアミン28.5ｇを得た。
収率71.3％
光学純度96.5％
〔α〕25 D＝＋38.88゜（無溶媒）
ベンゼン抽出の際に残つた水層に濃塩酸37.5ml
（0.36mol）を加え、３℃に冷却した後、析出し
た結晶を濾別し、28.5ｇの（−）―マンデル酸を
回収した。
回収率43.5％[Reference example 3] (±)-1-phenylethylamine 80.0g
Add (0.66 mmol) to 100 ml of water and add (-)-
65.5 g (0.43 mol) of mandelic acid was added and dissolved by heating. It was slowly cooled to 70℃, inoculated with 1.0g of seeds of (+)-1-phenylethylamine (-)-mandelate, cooled to 3℃, the precipitated crystals were filtered, and 75.5g ( 0.28 mol) of (+)-1-phenylethylamine/(-)-mandelate was obtained. Yield 83.7% Optical purity 96.3% [α] 25 435 = -108.5° (C = 1, 99% EtOH) To this, 100 ml of water and 13.6 g of sodium hydroxide were added.
After adding (0.34 mol) and extracting with benzene, the benzene layer was distilled under reduced pressure.
28.5 g of 1-phenylethylamine was obtained. Yield 71.3% Optical purity 96.5% [α] 25 D = +38.88゜ (no solvent) Add 37.5 ml of concentrated hydrochloric acid to the aqueous layer remaining during benzene extraction
(0.36 mol) was added, and after cooling to 3°C, the precipitated crystals were filtered off, and 28.5 g of (-)-mandelic acid was recovered. Recovery rate 43.5%
【実施例 １】
（±）―１―フエニルエチルアミン100.0ｇ
（0.83mol）を水115.0mlに加え、これに濃塩酸
36.2ml（0.41mol）および（＋）―マンデル酸
62.0ｇ（0.41mol）を加え加熱溶解した。70℃ま
で徐冷し、（−）―１―フエニルエチルアミン・
（＋）―マンデル酸塩の種を1.0ｇ接種し、５℃に
冷却した後、析出した結晶を濾別して97.0ｇ
（0.35mol）の（−）―１―フエニルエチルアミ
ン・（＋）―マンデル酸塩を得た。
収率86.0％
光学純度94.1％
〔α〕23 435＝＋108.8゜（Ｃ＝１，99％EtOH）
これを参考例１〜３と同様に処理し（−）―１
―フエニルエチルアミン37.2ｇを得た。
収率74.4％
光学純度94.4％
〔α〕25 D＝−38.04゜（無溶媒）
さらに（＋）―マンデル酸25.1ｇを回収した。
回収率40.5％。[Example 1] (±)-1-phenylethylamine 100.0g
(0.83mol) was added to 115.0ml of water, and concentrated hydrochloric acid was added to this.
36.2ml (0.41mol) and (+)-mandelic acid
62.0g (0.41mol) was added and dissolved by heating. Slowly cool to 70℃, (-)-1-phenylethylamine.
After inoculating 1.0g of (+)-mandelate seeds and cooling to 5℃, the precipitated crystals were filtered out and 97.0g
(0.35 mol) of (-)-1-phenylethylamine (+)-mandelate was obtained. Yield 86.0% Optical purity 94.1% [α] 23 435 = +108.8° (C = 1, 99% EtOH) This was treated in the same manner as Reference Examples 1 to 3 to obtain (-) -1
-37.2g of phenylethylamine was obtained. Yield: 74.4% Optical purity: 94.4% [α] 25 D = -38.04° (no solvent) In addition, 25.1 g of (+)-mandelic acid was recovered. Recovery rate 40.5%.
【実施例 ２】
（±）―１―フエニルエチルアミン121ｇ
（1.00mol）を水150mlに加え、これに（−）―マ
ンデル酸83ｇ（0.55mol）および濃塩酸39.0ml
（0.45mol）を加え、加熱溶解した。70℃まで徐
冷し、（＋）―１―フエニルエチルアミン・（−）
―マンデル酸塩を１ｇ接種した。10℃に冷却した
のち、析出した結晶を濾別し、112ｇ（0.41mol）
の（＋）―１―フエニルエチルアミン・（−）―
マンデル酸を得た。
これを実施例１と同様に処理して、（＋）―１
―フエニルエチルアミン44.2ｇを得た。
収率73％
光学純度96.8％。[Example 2] (±)-1-phenylethylamine 121g
(1.00 mol) was added to 150 ml of water, and to this was added 83 g (0.55 mol) of (-)-mandelic acid and 39.0 ml of concentrated hydrochloric acid.
(0.45 mol) was added and dissolved by heating. Slowly cool to 70℃, (+)-1-phenylethylamine・(-)
- 1 g of mandelate was inoculated. After cooling to 10℃, the precipitated crystals were filtered out and 112g (0.41mol)
(+)-1-Phenylethylamine・(-)-
Mandelic acid was obtained. This was processed in the same manner as in Example 1, and (+)-1
-44.2g of phenylethylamine was obtained. Yield 73%, optical purity 96.8%.
【実施例 ３】
（±）―１―フエニルエチルアミン12.10ｇ
（0.100mol）、（＋）―マンデル酸9.12ｇ
（0.060mol）および酢酸2.40ｇ（0.040mol）を水
17.0mlに加え、加熱溶解した。徐冷して70℃に至
つたところで、（−）―１―フエニルエチルアミ
ン・（＋）―マンデル酸塩0.1ｇを接種した。５℃
に冷却し、、析出した結晶を濾過して、11.94ｇの
（−）―１―フエニルエチルアミン・（＋）―マン
デル酸塩を得た（収率87.4％）。
これを水20mlおよびカセイソーダ2.1ｇに加え、
ベンゼンで抽出したのちベンゼンを除去し、減圧
蒸留により精製して（−）―１―フエニルエチル
アミン4.28ｇを得た。
収率70.8％
〔α〕20 D＝−39.2゜（無溶媒）
光学純度97.3％ee[Example 3] (±)-1-phenylethylamine 12.10g
(0.100mol), (+)-mandelic acid 9.12g
(0.060mol) and acetic acid 2.40g (0.040mol) in water.
The mixture was added to 17.0 ml and dissolved by heating. After slow cooling to 70°C, 0.1 g of (-)-1-phenylethylamine/(+)-mandelate was inoculated. 5℃
The precipitated crystals were filtered to obtain 11.94 g of (-)-1-phenylethylamine (+)-mandelate (yield: 87.4%). Add this to 20ml of water and 2.1g of caustic soda,
After extraction with benzene, the benzene was removed and purified by vacuum distillation to obtain 4.28 g of (-)-1-phenylethylamine. Yield 70.8% [α] 20 D = -39.2° (no solvent) Optical purity 97.3%ee
【実施例 ４】
（±）―１―フエニルエチルアミン12.10ｇ
（0.100mol）、（＋）―マンデル酸7.60ｇ
（0.050mol）および酢酸3.00ｇ（0.050mol）を水
15.0mlに加え、加熱溶解した。徐冷して70℃で種
晶0.1ｇを加え、５℃に冷却して析出した結晶を
濾別することにより、11.12ｇの（−）―１―フ
エニルエチルアミン・（＋）―マンデル酸塩を得
た（収率81.5％）。
これを実施例３と同様に処理して、（−）―１
―フエニルエチルアミン4.02ｇを得た。
収率66.4％
〔α〕20 D＝−38.0゜（無溶媒）
光学純度94.3％ee[Example 4] (±)-1-phenylethylamine 12.10g
(0.100mol), (+)-mandelic acid 7.60g
(0.050mol) and 3.00g (0.050mol) of acetic acid in water.
The mixture was added to 15.0 ml and dissolved by heating. After cooling slowly to 70°C, add 0.1g of seed crystals, cool to 5°C, and filter out the precipitated crystals to obtain 11.12g of (-)-1-phenylethylamine/(+)-mandelate. was obtained (yield 81.5%). This was processed in the same manner as in Example 3, and (-)-1
-4.02g of phenylethylamine was obtained. Yield 66.4% [α] 20 D = -38.0° (no solvent) Optical purity 94.3%ee
【実施例 ５】
（±）―１―フエニルエチルアミン12.10ｇ
（0.100mol）、（＋）―マンデル酸10.64ｇ
（0.070mol）および濃硫酸0.84ml（0.015mol）を
水19.0mlに加え、加熱溶解した。徐冷して70℃で
種晶0.1ｇを加え、５℃に冷却して析出した結晶
を濾別することにより、11.85ｇの（−）―１―
フエニルエチルアミン・（＋）―マンデル酸塩を
得た（収率86.8％）。
これを実施例３と同様に処理して、（−）―１
―フエニルエチルアミン4.37ｇを得た。
収率72.2％
〔α〕20 D＝−39.0゜（無溶媒）
光学純度96.8％ee[Example 5] (±)-1-phenylethylamine 12.10g
(0.100mol), (+)-mandelic acid 10.64g
(0.070 mol) and 0.84 ml (0.015 mol) of concentrated sulfuric acid were added to 19.0 ml of water and dissolved by heating. After cooling slowly and adding 0.1 g of seed crystals at 70°C, cooling to 5°C and filtering out the precipitated crystals, 11.85 g of (-)-1-
Phenylethylamine (+)-mandelate was obtained (yield 86.8%). This was processed in the same manner as in Example 3, and (-)-1
-4.37g of phenylethylamine was obtained. Yield 72.2% [α] 20 D = -39.0° (no solvent) Optical purity 96.8%ee
【参考例 ４】
（±）―１―フエニルエチルアミン12.10ｇ
（0.100mol）、（＋）―マンデル酸7.60ｇ
（0.050mol）を水15.0mlとともに加熱し、溶解し
た。徐冷して53℃で種晶0.1ｇを加え、５℃まで
冷却した。析出した結晶を濾過して、8.20ｇの
（−）―１―フエニルエチルアミン・（＋）―マン
デル酸塩を得た（収率60.0％）。
これを実施例３と同様に処理して、（−）―フ
エニルエチルアミン2.90ｇを得た。
収率47.9％
〔α〕20 D＝−39.7゜（無溶媒）
光学純度98.5％ee[Reference example 4] (±)-1-phenylethylamine 12.10g
(0.100mol), (+)-mandelic acid 7.60g
(0.050 mol) was heated with 15.0 ml of water and dissolved. After slow cooling, 0.1 g of seed crystals was added at 53°C, and the mixture was cooled to 5°C. The precipitated crystals were filtered to obtain 8.20 g of (-)-1-phenylethylamine/(+)-mandelate (yield 60.0%). This was treated in the same manner as in Example 3 to obtain 2.90 g of (-)-phenylethylamine. Yield 47.9% [α] 20 D = -39.7° (no solvent) Optical purity 98.5%ee
本発明の方法により、光学活性１―フエニルエ
チルアミンが、高い光学純度で得られる。媒体と
して水を使用するから、工程は簡単であり、コス
トも低廉である。
By the method of the present invention, optically active 1-phenylethylamine is obtained with high optical purity. Since water is used as a medium, the process is simple and the cost is low.
Claims (1)
割して光学活性１―フエニルエチルアミンを製造
する方法において、媒体中で（±）―１―フエニ
ルエチルアミンに対し光学活性なマンデル酸を作
用させ、生成したジアステレオマー塩の溶解度差
を利用して光学分割を行なうことからなり、媒体
として、ジアステレオマー混合物中に存在する難
溶性１―フエニルエチルアミン・マンデル酸塩に
対し等量ないし２倍量の水を使用し、かつ溶解性
（±）―１―フエニルエチルアミン塩を共存させ
ることを特徴とする光学活性１―フエニルエチル
アミンの製造方法。 ２ 溶解性（±）―１―フエニルエチルアミン塩
を光学活性マンデル酸に対してほぼ等モル使用し
て実施する特許請求の範囲第１項に記載の製造方
法。[Claims] 1. A method for producing optically active 1-phenylethylamine by optically resolving (±)-1-phenylethylamine, in which optically active 1-phenylethylamine is produced with respect to (±)-1-phenylethylamine in a medium. This method involves applying mandelic acid and performing optical resolution by utilizing the solubility difference between the diastereomer salts produced. 1. A method for producing optically active 1-phenylethylamine, which is characterized by using an equivalent to twice the amount of water and allowing a soluble (±)-1-phenylethylamine salt to coexist. 2. The manufacturing method according to claim 1, wherein the soluble (±)-1-phenylethylamine salt is used in approximately equimolar amounts to the optically active mandelic acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10226179A JPS5626848A (en) | 1979-08-13 | 1979-08-13 | Optical resolution of (+-)-1-phenylethylamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10226179A JPS5626848A (en) | 1979-08-13 | 1979-08-13 | Optical resolution of (+-)-1-phenylethylamine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5626848A JPS5626848A (en) | 1981-03-16 |
| JPH024581B2 true JPH024581B2 (en) | 1990-01-29 |
Family
ID=14322644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10226179A Granted JPS5626848A (en) | 1979-08-13 | 1979-08-13 | Optical resolution of (+-)-1-phenylethylamine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5626848A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6354342A (en) * | 1986-08-26 | 1988-03-08 | Daicel Chem Ind Ltd | Optical resolution of (+-)-alpha-ethylbenzylamine |
| JP4768145B2 (en) * | 2001-04-18 | 2011-09-07 | 大東化学株式会社 | Optical purification method of optically active 2-phenoxypropionic acid |
| US7968703B2 (en) | 2005-03-07 | 2011-06-28 | Shire Canada Inc. | Process and methods for the preparation of optically active cis-2-hydroxymethyl-4- (cytosin-1'-yl)-1,3-oxathiolane or pharmaceutically acceptable salts thereof |
| JP2008169204A (en) * | 2006-12-15 | 2008-07-24 | Sumitomo Chemical Co Ltd | Method for preparing (1r, 2r)-2-amino-1-cyclopentanol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4718737U (en) * | 1971-04-05 | 1972-11-01 |
-
1979
- 1979-08-13 JP JP10226179A patent/JPS5626848A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS4718737U (en) * | 1971-04-05 | 1972-11-01 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5626848A (en) | 1981-03-16 |
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