JPS58177933A - Optical resolution of dl-mandelic acid - Google Patents
Optical resolution of dl-mandelic acidInfo
- Publication number
- JPS58177933A JPS58177933A JP5802482A JP5802482A JPS58177933A JP S58177933 A JPS58177933 A JP S58177933A JP 5802482 A JP5802482 A JP 5802482A JP 5802482 A JP5802482 A JP 5802482A JP S58177933 A JPS58177933 A JP S58177933A
- Authority
- JP
- Japan
- Prior art keywords
- mandelic acid
- dmcla
- salt
- optically active
- caprolactam
- 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.)
- Pending
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
本発明はＤＬ−マノデル酸の光学分割方法に関するもの
である。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for optical resolution of DL-manoderic acid.
マンデル酸の光学活性体は、アミン化合物に代表される
塩基性化合物の光学分割剤として有用な化合物であり（
Ｓ、 Ｈ，Ｗｉｌｅｎら、 ’ Ｅｎａｎｔｉｏｍｅｒ
ｓ 。The optically active form of mandelic acid is a compound useful as an optical resolving agent for basic compounds such as amine compounds (
S. H. Wilen et al. 'Enantiomer
s.
Ｒａｃｅｍａｔｅｓ 、 ａｎｄ Ｒｅ５ｏｌｕｔｉｏ
ｎｓ ’ 、 Ｊｏｈｎ Ｗｉｌｅｙ４Ｓｏｎｓ 。Racemates, and Re5olution
ns', John Wiley4Sons.
（１９８１））、特に、Ｄ−マンデル酸はセファロスポ
リン系あるいはペニシリン系抗生物質を合成する際の原
料として有用な化合物である。(1981)), in particular, D-mandelic acid is a compound useful as a raw material for synthesizing cephalosporin or penicillin antibiotics.
従来、このマノデル酸の光学活性体を得る方法として、
エフニド・リン（Ｒ，Ｒｏｇｅｒ 、 Ｊ、 Ｃｈｅ
ｍ。Conventionally, as a method for obtaining this optically active form of manoderic acid,
Efnid Lin (R, Roger, J, Che
m.
Ｓｏｃ、 、１５４４ （１９３５） ’）、シ：／
コ＝ ン’ ＣＡ。Soc, , 1544 (1935)'), shi:/
Con' CA.
Ｍａｃｋｅｎｚｉｅ 、 Ｊ、 Ｃｈｅｍ、 Ｓｏｃ
、 、 ９６６ （１８９９） ’］、フェニルエチ
ルアミンＣＡ、 Ｗ、 Ｉｎｇｅｒｓｏｌｌら、Ｊ。Mackenzie, J., Chem, Soc.
, 966 (1899)'], Phenylethylamine CA, W, Ingersoll et al., J.
Ａｍｅｒ、Ｃｈｅｍ、 Ｓｏｃ、、 ５５ 、ｒ、４１
１ 、 （１９３３） ）あるいは２−アミノブタノー
ル（特開昭５４−２４８９号公報）を分割剤に用いるジ
アステレオマー法が知られている。Amer, Chem, Soc,, 55, r, 41
1, (1933)) or 2-aminobutanol (JP-A-54-2489) as a resolving agent is known.
シカシ、上記エフェドリンやシンフニンのようなアルカ
ロイド類は大量にしかも安価に入手し難いうえ化合物に
よっては毒性を有しており、しかも、分割効率が悪いな
ど、工業的に用いるには難点がある。また、上記２−ア
ミノブタノールを用いる分割法は工業的に用いるには分
割剤の回収方法が繁雑であるなどの欠点がある。Alkaloids such as ephedrine and synfunin are difficult to obtain in large quantities and at low cost, and some compounds are toxic, and their splitting efficiency is poor, making them difficult to use industrially. Furthermore, the above-mentioned resolution method using 2-aminobutanol has drawbacks such as the complicated method for recovering the resolving agent for industrial use.
また、マンデル酸の光学、分割法として、ジイソプロピ
ルアミン（特開昭５５−１１３７３８号公報）、Ｎ−メ
チルシクロヘキシルアミンあるいはピペリジン（特開昭
５６ １２２３２号公報）等の塩基を使用する優先晶出
法も知られている。しかし、この方法は低収率であり工
業的に使用するには未だ問題力（ある。In addition, as an optical resolution method for mandelic acid, a preferential crystallization method using a base such as diisopropylamine (Japanese Unexamined Patent Publication No. 55-113738), N-methylcyclohexylamine or piperidine (Japanese Unexamined Patent Publication No. 56-12232) is also available. is also known. However, this method has a low yield and is still problematic for industrial use.
そこで、本発明者らは、上記しｔコ公知方法以上に有利
に、ＤＬ−マンデＪし酸を光学公害」する方法について
種々検討を重ねｔコ結果、溶媒中でＤＬ−マンデル酸に
α−ジメチルアミノ−ε−カプロラクタムの光学活性体
を作用させる方法（レアステレオマ−法）によって、高
収率で力）つ安定的に高純度のマンデル酸光学活性体を
９得ることができることを見０出し、本発明をなすに至
った。Therefore, the present inventors have conducted various studies on a method for optically polluting DL-mandelic acid, which is more advantageous than the above-mentioned known methods, and have found that DL-mandelic acid can be converted to α-mandelic acid in a solvent. It was found that optically active form of mandelic acid 9 can be obtained stably and in high yield and purity by a method of acting with optically active form of dimethylamino-ε-caprolactam (rare stereomer method). This led to the present invention.
マンデル酸およびα−ジメチルアミノ−ε−カプロラク
タムは各々、次式１および１で示されろ。Mandelic acid and α-dimethylamino-ε-caprolactam are represented by the following formulas 1 and 1, respectively.
■？
（式１） （式ｌ）
本発明で使用するα−ジメチルアミノ−ε−カプロラク
タムの光学活性体は、例えば、光学活性のσ−アミノー
ε−カプロラクタム番こホルムアルテヒトを反応させる
（ Ｅｓｃｈｗｅｉｌｅｒ Ｃｌａｒｋｅ反応）ことに
より製造することができる（特開昭５４−７６５９０号
公報）。あるいは、ＤＬ−α−ジメチルアミノ−ε−カ
プロラクタムをマンデル酸の光学活性体の如き分割剤で
光学分割して、その光学活性体を取得することもできる
。■? (Formula 1) (Formula 1) The optically active form of α-dimethylamino-ε-caprolactam used in the present invention can be obtained by, for example, reacting optically active σ-amino-ε-caprolactam with formaldehyde (Eschweiler Clarke reaction). (JP-A-54-76590). Alternatively, an optically active form of DL-α-dimethylamino-ε-caprolactam can be obtained by optically resolving DL-α-dimethylamino-ε-caprolactam using a resolving agent such as an optically active form of mandelic acid.
本発明で用いる分割剤は、α−ジメチルアミノ−ε−カ
プロラクタムの光学活性体であり、そのＤ一体およびＬ
一体（以下、各々Ｄ Ｃ＋ｌ −ＤＭＣＬＡ、Ｌ←）−
ＤＭＣＬＡと略す）の０ずれを用いることもできる。例
えば、適当な溶媒中でＤＬ−マンデル酸に等モＪし量の
Ｄ（−１−）−ＤＭＣＬＡを作用させれば、Ｄ−ＭＡ−
Ｄ−ＤＭＣＬＡ塩とＬ −ＭＡ ＠Ｄ−ＤＭＣＬＡ塩と
の２種のジアステレオマー塩が生成する（なお、Ｄ−Ｍ
ＡおよびＬ−ＭＡは、各々マノデル酸のＤ一体およびＬ
一体を示す）。これら２種のジアステレオマー塩はその
溶解度に顕著な差があるので、その溶液を冷却あるいは
濃縮などして難溶性塩であるＬ−ＭＡ ＠Ｄ−ＤＭＣＬ
Ａ塩の１１を選択的に晶出させることができる。一方、
分割剤としてＬ （−１−Ｄ Ｍ ＣＬ Ａを用いる場
合には、Ｄ−ＭＡ＠Ｌ−ＤＭＣＬＡ塩とＬ・−ＭＡ・Ｌ
−ＤＭＣＬＡ塩との２種のジアステレオマー塩が生成す
るので、難溶性のＤ−ＭＡ−Ｌ−ＤＭＣＬＡ塩を上記と
同様の方法で晶出することができる。The resolving agent used in the present invention is an optically active form of α-dimethylamino-ε-caprolactam.
Together (hereinafter, each D C+l −DMCLA, L←) −
It is also possible to use zero deviation of DMCLA). For example, if DL-mandelic acid is treated with an equal amount of D(-1-)-DMCLA in a suitable solvent, D-MA-
Two types of diastereomeric salts, D-DMCLA salt and L-MA@D-DMCLA salt, are generated (in addition, D-M
A and L-MA are D and L of manoderic acid, respectively.
). Since these two types of diastereomeric salts have a remarkable difference in solubility, the solution is cooled or concentrated to dissolve the poorly soluble salt L-MA @D-DMCL.
A salt 11 can be selectively crystallized. on the other hand,
When L (-1-D MCL A is used as a resolving agent, D-MA@L-DMCLA salt and L・-MA・L
Since two types of diastereomeric salts with the -DMCLA salt are generated, the sparingly soluble D-MA-L-DMCLA salt can be crystallized in the same manner as above.
かくして本発明によって得られる各ジアステレオマー塩
は常法によって酸、アルカリによる中和、あるいはイオ
ン交換等の処理をして各成分を分離、採取することがで
きる。Each diastereomer salt thus obtained according to the present invention can be subjected to treatments such as neutralization with acid or alkali or ion exchange in a conventional manner to separate and collect each component.
本発明において使用する溶媒としてはマンデル酸とα−
ジメチルアミノ−Ｃ−カプロラクタムを溶解するととも
に、溶液中でこれら化合物を化学的に変質せしめること
なく、かつ、前記ジアステレオマー塩を析出せしめるも
のであれば特に制限はなく、通常、低級アルコール類、
低級ケトン類、低級エステル類あるいは低級エーテル類
を使用すればよい。溶液の具体例としては、メタノール
、エタノール、アセトン、メチルエチルケトノ、酢酸エ
チル、１．４−ジオキサン、テトラヒドロフラン等ある
いはこれら溶媒の混合物をあげることができる。またこ
れら溶媒の希釈剤として水を用いてもよい。この場合、
目的とするジアステレオマー塩の取得率を下げる傾向は
あるが、その光学純度には全く影響をあたえない。The solvents used in the present invention include mandelic acid and α-
There is no particular restriction as long as it dissolves dimethylamino-C-caprolactam, does not chemically alter these compounds in solution, and precipitates the diastereomer salt, and usually lower alcohols,
Lower ketones, lower esters, or lower ethers may be used. Specific examples of the solution include methanol, ethanol, acetone, methyl ethyl ketone, ethyl acetate, 1,4-dioxane, tetrahydrofuran, and mixtures of these solvents. Furthermore, water may be used as a diluent for these solvents. in this case,
Although it tends to lower the yield of the desired diastereomeric salt, it does not affect its optical purity at all.
本発明において、ＤＬ−マンデル酸にＤ ｕｌ −ＤＭ
ＣＬＡもしくはＬ（→−ＤＭＣＬＡの分割剤を作用させ
る方法としては、上記した溶媒中にＤＬ−マンデル酸お
よび分割剤を別個に溶解して混合してもよいし、また、
溶媒中にそれらを順次溶解してもよい。さらにあらかじ
め、ＤＬ−マンデル酸と分割剤とで作成した塩を該溶媒
中、に添加溶解してもよい。In the present invention, Dul-DM is added to DL-mandelic acid.
As a method for causing the resolving agent of CLA or L(→-DMCLA to act, DL-mandelic acid and the resolving agent may be dissolved separately in the above-mentioned solvent and mixed, or,
They may be sequentially dissolved in a solvent. Furthermore, a salt prepared from DL-mandelic acid and a resolving agent may be added and dissolved in the solvent in advance.
分割剤の使用量には特に制限はないが、ＤＬ−マノデル
酸に対して等モル量も使用すれば充分である。難溶性塩
を分割溶媒から析出させる際の温度条件としては使用す
る溶媒の凝固点から沸点の範囲であればよく、目的に応
じて適宜法められるが、通常０℃から１００℃の範囲で
充分である。There is no particular restriction on the amount of the resolving agent used, but it is sufficient to use an equimolar amount with respect to DL-manoderic acid. The temperature conditions for precipitating the poorly soluble salt from the splitting solvent may be within the range from the freezing point to the boiling point of the solvent used, and may be determined as appropriate depending on the purpose, but usually a temperature in the range of 0°C to 100°C is sufficient. be.
かくして本発明によれば、ＤＬ−マンデル酸を極めて簡
単な方法で光学分割して、光学純度の高いマンデル酸光
学活性体を容易に得ることができる。Thus, according to the present invention, an optically active form of mandelic acid with high optical purity can be easily obtained by optically resolving DL-mandelic acid using an extremely simple method.
種々のジアステレオマー塩の物性を表１に示した。Table 1 shows the physical properties of various diastereomeric salts.
表 １ 次に、実施例により本発明をさらに説明する。Table 1 Next, the present invention will be further explained by examples.
実施例Ｉ
ＤＬ−マンデル酸３．０４１とＬ−ＤＭＣＬＡ〔比旋光
度〔０片−−２９，３°（Ｃ＝２．Ｈ２Ｏ） 〕３、１
２ ｆｌとをアセトン６０ ａｔに加温溶解した。Example I DL-mandelic acid 3.041 and L-DMCLA [specific optical rotation [0 piece - -29,3° (C=2.H2O)] 3,1
2 fl was dissolved under heating in 60 at of acetone.
攪拌しながら３５℃においてＤ−ＭＡ−Ｌ−ＤＭＣＬＡ
塩０．１０ ｆを接種した。接種と同時にこの溶液の冷
却を始め、２時間かけて１５℃まで冷却したところ塩の
結晶が多量析出した。D-MA-L-DMCLA at 35°C with stirring
Inoculated with 0.10 f salt. Cooling of this solution was started at the same time as the inoculation, and when the solution was cooled to 15° C. over 2 hours, a large amount of salt crystals precipitated.
これをろ別後、乾燥して１．８１１のＤ−ＭＡ・Ｌ−Ｄ
ＭＣＬＡ塩を得た（晶析率２８％、光学純度７５％、分
割率４１％）。After filtering this and drying it, 1.811 D-MA/LD
MCLA salt was obtained (crystallization rate 28%, optical purity 75%, resolution 41%).
得られた結晶の全量を水１０ ｓ／に溶解し、強酸性陽
イオン交換樹脂ゞダイアイオンＰＫ２１６ ’（三菱化
成工業（株）製）２０ｇ／を充填した樹脂塔に通液して
、Ｄ−マンデル酸を含む水溶液を得た。該水溶液および
樹脂塔の洗浄水をロータリエバポレーターで減圧下で濃
縮、乾固してＤ−マンデル酸をほぼ定量的に得た。得ら
れたＤ−マンデル酸の比旋光度は〔α〕背−−１１９．
０゜（Ｃ＝２、Ｈ２Ｏ）であった。The entire amount of the obtained crystals was dissolved in 10 s of water and passed through a resin tower filled with 20 g of a strongly acidic cation exchange resin Diaion PK216' (manufactured by Mitsubishi Chemical Industries, Ltd.) to obtain D- An aqueous solution containing mandelic acid was obtained. The aqueous solution and the washing water from the resin tower were concentrated and dried under reduced pressure using a rotary evaporator to obtain D-mandelic acid almost quantitatively. The specific optical rotation of the obtained D-mandelic acid is [α] -119.
0° (C=2, H2O).
実施例２〜８
実施例１における溶媒あるいは分割剤を変えた以外は、
実施例１と同様な方法で実施し、その結果を表２に示し
た。Examples 2 to 8 Except for changing the solvent or resolving agent in Example 1,
It was carried out in the same manner as in Example 1, and the results are shown in Table 2.
Claims (1)
を分割剤としてＤＬ−マンデル酸を光学分割することを
特徴とするＤＬ−マンデル酸の光学分割方法。1. A method for optically resolving DL-mandelic acid, which comprises optically resolving DL-mandelic acid using an optically active form of α-dimethylamino-ε-caprolactam as a resolving agent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5802482A JPS58177933A (en) | 1982-04-09 | 1982-04-09 | Optical resolution of dl-mandelic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5802482A JPS58177933A (en) | 1982-04-09 | 1982-04-09 | Optical resolution of dl-mandelic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58177933A true JPS58177933A (en) | 1983-10-18 |
Family
ID=13072376
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5802482A Pending JPS58177933A (en) | 1982-04-09 | 1982-04-09 | Optical resolution of dl-mandelic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58177933A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5296373A (en) * | 1991-06-26 | 1994-03-22 | Nitto Chemical Industry Co., Ltd. | Process for producing R(-)-mandelic acid or a derivative thereof from a mandelonitrile using rhodococcus |
| EP2574667A1 (en) | 2011-10-02 | 2013-04-03 | Technische Universität Graz | Enzyme variants |
-
1982
- 1982-04-09 JP JP5802482A patent/JPS58177933A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5296373A (en) * | 1991-06-26 | 1994-03-22 | Nitto Chemical Industry Co., Ltd. | Process for producing R(-)-mandelic acid or a derivative thereof from a mandelonitrile using rhodococcus |
| EP2574667A1 (en) | 2011-10-02 | 2013-04-03 | Technische Universität Graz | Enzyme variants |
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