KR19980059278A - Racemization of Phenylglycine Derivatives with Optical Activity - Google Patents
Racemization of Phenylglycine Derivatives with Optical Activity Download PDFInfo
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- KR19980059278A KR19980059278A KR1019960078615A KR19960078615A KR19980059278A KR 19980059278 A KR19980059278 A KR 19980059278A KR 1019960078615 A KR1019960078615 A KR 1019960078615A KR 19960078615 A KR19960078615 A KR 19960078615A KR 19980059278 A KR19980059278 A KR 19980059278A
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- C07C227/36—Racemisation of optical isomers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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Abstract
본 발명은 광학활성을 갖는 페닐글리신 유도체의 라세미화 방법에 관한 것으로서, 더욱 상세하기로는 광학활성을 갖는 페닐글리신 유도체에 고주파 음파를 적용시켜 다음 화학식 1로 표시되는 라세믹 D,L-페닐글리신 유도체로 라세미화하는 방법에 관한 것이다.The present invention relates to a racemization method of a phenylglycine derivative having optical activity, and more particularly, to a racemic D, L-phenylglycine derivative represented by Formula 1 by applying high frequency sound waves to a phenylglycine derivative having optical activity. To a method of racemization.
상기 화학식에서, R은 수소원자, 하이드록시기 또는 C1~ C4의 알킬기이다.In the above formula, R is a hydrogen atom, a hydroxy group or a C 1 ~ C 4 alkyl group.
Description
본 발명은 광학활성을 갖는 페닐글리신 유도체의 라세미화 방법에 관한 것으로서, 더욱 상세하기로는 광학활성을 갖는 페닐글리신 유도체에 고주파 음파를 적용시켜 다음 화학식 1로 표시되는 라세믹 D,L-페닐글리신 유도체로 라세미화하는 방법에 관한 것이다.The present invention relates to a racemization method of a phenylglycine derivative having optical activity, and more particularly, to a racemic D, L-phenylglycine derivative represented by Formula 1 by applying high frequency sound waves to a phenylglycine derivative having optical activity. To a method of racemization.
[화학식 1][Formula 1]
상기 화학식에서, R은 수소원자, 히드록시기 또는 C1~ C4의 알킬기이다.In the above formula, R is a hydrogen atom, a hydroxy group or an alkyl group of C 1 ~ C 4 .
페닐글리신 유도체은 자연계에서 얻을 수 없는 아미노산으로서 주로 공업적으로 제조하고 있으며 의약품 제조시 중간체로서 사용되고 있는 중요 물질이다. 특히, 페니실린계 항생제, 세파로스로린계 항생제인 아목시실린, 세파드록실, 엠피실린, 세파렉신, 세파클러 등의 제조에서 핵심 중간체로 이용되고 있다.Phenylglycine derivatives are amino acids that cannot be obtained in nature and are mainly produced industrially and are important substances used as intermediates in the manufacture of pharmaceuticals. In particular, penicillin-based antibiotics, Sepharoserin-based antibiotics Amoxicillin, Sephadroxyl, Empicillin, Separexin, Sephacler and the like are used as a key intermediate in the manufacture.
공업적인 페닐글리신 유도체의 제조방법에서는 D-페닐글리신 유도체와 L-페닐글리신 유도체의 두가지 입체이성질체들이 섞여 있는 혼합물로 생산된 후, 이들을 화학적인 방법이나 생물학적인 방법 등으로 분할하여 D-페닐글리신 유도체만을 얻어 페니실린계 항생제, 세파로스로린계 항생제등에 핵심원료로 이용하고 있다. 또한, 분할후 남은 불필요한 L-페닐글리신 유도체는 다시 라세미화하여 두가지 입체이성질체들이 섞여 있는 혼합물로 재변환시킨 후, D-페닐글리신 유도체의 제조에 이용하고 있다. 따라서 광학 활성을 갖는 L-페닐글리신 등을 라세미화하는 방법은 상업적으로 광학활성을 갖는 페닐글리신 유도체를 제조하는데 있어 핵심기술로서 공업적으로 매우 중요하다.In the process for the production of industrial phenylglycine derivatives, D-phenylglycine derivatives are produced as a mixture of two stereoisomers of D-phenylglycine derivatives and L-phenylglycine derivatives, and then divided into chemical or biological methods. It is used as a key raw material for penicillin antibiotics and sepharoserin antibiotics. In addition, the unnecessary L-phenylglycine derivatives remaining after cleavage are again racemized and reconverted into a mixture containing two stereoisomers, which are then used to prepare the D-phenylglycine derivatives. Therefore, the method of racemizing L-phenylglycine and the like having optical activity is very important industrially as a core technology in preparing commercially active phenylglycine derivatives.
광학활성을 갖는 아미노산의 라세미화하는 방법은 이미 여러 문헌에 보고되고 있다.The method of racemization of amino acids having optical activity has already been reported in various literatures.
광학활성을 갖는 페닐글리신 유도체의 수용액을 염산, 황산 등의 강산이나 수산화나트륨, 수산화칼륨 등의 강염기의 존재하에서 고온으로 가열하여 라세미화하는 방법이 공지되어 있다[Advances in Protein Chemistry, Vol.4, p.4339(1948)]. 그러나 이러한 조건을 상업적인 생산에 적용하기에는 반응시간이 지나치게 길고, 반응온도가 고온이며, 아미노산이 분해되어 불순물이 다량 생성되는 단점을 가지고 있어 이를 개선하기 위한 많은 연구들이 이루어졌다.A method of racemizing an aqueous solution of an optically active phenylglycine derivative at high temperature in the presence of strong acids such as hydrochloric acid and sulfuric acid or strong bases such as sodium hydroxide and potassium hydroxide is known [Advances in Protein Chemistry, Vol. 4, p. 4339 (1948)]. However, there are many studies to improve this condition because the reaction time is too long, the reaction temperature is high, and the amino acid is decomposed to produce a large amount of impurities.
예컨대, 용매로서 물 대신에 초산, 프로피온산 등의 약한 유기산을 사용하여 좀더 온화한 조건에서 광학활성을 갖는 아미노산의 라세미화 반응을 통해 라세믹 D,L-아미노산을 얻은 바도 있다[Chem. Pharm. Bull., Vol.18, p.1788(1970)]. 이를 개선하기 위한 방법으로서, L-페닐글리신이나 L-파라-히드록시페닐글리신을 초산, 프로피온산 등을 용매로 하고 여러 종류의 알데히드를 촉매로 사용하여 100℃에서 2시간 교반하므로써 90% ~ 93%의 높은 수율로 라세믹 D,L-페닐글리신이나 D,L-파라-히드록시페닐글리신을 얻은 바도 있다[미국특허 제4,401,820호(1983)]. 그러나 이러한 라세미화 방법들은 반응용매로서 유기산을 사용하기 때문에 유기용매를 회수하기 위한 별도의 까다로운 공정이 요구되고, 유기용매의 독성이나 독한 냄새가 커다란 문제점으로 남아 있다.For example, racemic D, L-amino acids have been obtained through racemization of optically active amino acids under milder conditions using weak organic acids such as acetic acid and propionic acid as solvents [Chem. Pharm. Bull., Vol. 18, p. 1788 (1970). As a method for improving this, 90% to 93% by stirring L-phenylglycine or L-para-hydroxyphenylglycine as acetic acid, propionic acid as a solvent and using various kinds of aldehydes as a catalyst for 2 hours at 100 ° C Racemic D, L-phenylglycine or D, L-para-hydroxyphenylglycine have been obtained in high yield of US Pat. No. 4,401,820 (1983). However, since these racemization methods use organic acids as reaction solvents, a separate and demanding process for recovering organic solvents is required, and the toxicity or poisonous smell of organic solvents remains a significant problem.
그리고 일본공개특허 소48-67230호에서는 강산이나 강염기를 사용하지 않고 밀폐된 반응기를 이용하여 가압하에서 광학활성을 갖는 아미노산의 수용액을 물의 비점 이상의 온도인 160℃에서 6 시간동안 라세미화 반응을 진행시켜 불순물 없이 높은 수율로 라세믹 D,L-페닐글리신 유도체를 얻었다고 기술하고 있다. 이 방법에서는 용매의 비점 이상의 고온 유지를 위하여 밀폐된 용기를 사용하므로써 고압 효과를 얻고 있다.In Japanese Patent Application Laid-Open No. 48-67230, the racemization reaction is carried out for 6 hours at 160 ° C., which is a temperature above the boiling point of water, by using an enclosed reactor without using a strong acid or strong base. It is described that racemic D, L-phenylglycine derivatives were obtained in high yield without impurities. In this method, a high pressure effect is obtained by using a sealed container for maintaining a high temperature above the boiling point of the solvent.
한편, 고주파 음파를 사용하는 반응에 대한 연구에서 일반적으로 받아들여지고 있는 '핫-스팟(hot-spot)' 이론에 의하면 반응 매개물내에 도입된 고주파의 음파는 매개물인 용매내에 순간적으로 눈으로는 볼 수 없을 정도의 아주 작은 공동들을 형성하며 이 공동이 붕괴되는 과정에서 일순간 국부적으로 1000℃ 이상의 아주 높은온도와 1000 bar 이상의 높은 압력을 발생시키게 된다. 이러한 효과는 다양한 반응에서 반응속도를 증가시켜 반응시간을 줄이고, 수율과 선택성을 향상시키며 많은 경우에 초음파는 보통의 반응에 요구되는 온도와 압력을 상당히 줄일 수 있어 산업적으로 매우 유용한 것으로 알려져 있다.On the other hand, according to the 'hot-spot' theory generally accepted in the study of the reaction using high frequency sound waves, the high frequency sound waves introduced in the reaction medium are instantaneously visible in the medium solvent. They form innumerably tiny cavities, and in the course of their collapse they generate localized very high temperatures of over 1000 ° C and high pressures over 1000 bar. This effect is known to be very useful industrially by increasing the reaction rate in various reactions to reduce the reaction time, improve the yield and selectivity, and in many cases ultrasonic waves can significantly reduce the temperature and pressure required for the normal reaction.
최근 다양한 반응에 초음파를 이용하고 있다. 예를들면, o-퀴논과 디엔의 딜스엘더(Diels-Alder) 고리화반응에서는 11 kbar 이상의 고압 조건하에서만이 가능한 라세미화 반응을 50 ~ 60 kHz의 고주파 음파를 사용하여 상압조건하에서도 동일한 효과를 얻고 있음이 보고된 바 있다[J. Am. Chem. Soc., Vol.111, p.1522(1989)]. 또한, 수소주석화 반응과 수소화 환원반응에 초음파를 도입함으로써 통상적으로 50 ~ 100℃에서 진행되는 반응을 0℃ 정도로 낮추는 효과를 확인한 바도 있다[J. Am. Chem. Soc., Vol.111, p.6849(1989)]. 즉, 상기와 같은 효과는 고주파 음파의 공동의 붕괴시 국부적이고 순간적으로 생성되는 1000℃ 이상의 고온효과에 의한 것이다.Recently, ultrasonic waves have been used for various reactions. For example, in the Diels-Alder cyclization of o-quinone and diene, the same effect can be achieved under normal pressure conditions using a high-frequency sound wave of 50 to 60 kHz. Has been reported [J. Am. Chem. Soc., Vol. 111, p. 1522 (1989). In addition, by introducing ultrasonic waves into the hydrogen tinization reaction and hydrogenation reduction reaction has been confirmed that the effect of lowering the reaction usually proceeds at 50 ~ 100 ℃ to about 0 ℃ [J. Am. Chem. Soc., Vol. 111, p. 6849 (1989). That is, the above effect is due to the high temperature effect of 1000 ° C. or higher generated locally and instantaneously when the cavity of the high frequency sound wave collapses.
본발명에서는 광학활성을 갖는 페닐글리신 유도체를 라세미화하는 과정에서 고주파 음파를 이용한다면 보다 온화한 반응조건으로도 고수율의 라세믹 D,L-페닐글리신 유도체를 얻을 수 있음을 알게됨으로써 본 발명을 완성하였다.In the present invention, the use of high-frequency sound waves in the process of racemizing the phenylglycine derivative having optical activity to obtain a high yield of racemic D, L-phenylglycine derivative even under milder reaction conditions to complete the present invention It was.
따라서, 본 발명은 광학활성을 가지는 페닐글리신 유도체에 고주파 음파를 적용하여 온화한 반응조건으로 라세미화하는 방법을 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a method of racemization under mild reaction conditions by applying high frequency sound waves to phenylglycine derivatives having optical activity.
도1은 본 발명에서 이용되는 반응장치를 개략적으로 도시한 것이다.Figure 1 schematically shows a reactor used in the present invention.
본 발명은 광학활성을 갖는 페닐글리신 유도체를 라세미화하여 다음 화학식 1로 표시되는 라세믹 D,L-페닐글리신 유도체를 제조하는 방법에 있어서, 20 ~ 60 kHz의 고주파 음파를 적용하여 산이나 염기를 사용하지 않고 상압 및 수용액 조건하에서 페닐글리신 유도체를 라세미화하는 것을 그 특징으로 한다.The present invention is a method for producing a racemic D, L-phenylglycine derivative represented by the following Formula 1 by racemizing a phenylglycine derivative having an optical activity, by applying a high frequency sound wave of 20 ~ 60 kHz to acid or base It is characterized by the racemization of phenylglycine derivatives under normal pressure and aqueous solution without use.
화학식 1Formula 1
상기 화학식에서, R은 수소원자, 히드록시기 또는 C1~ C4의 알킬기이다.In the above formula, R is a hydrogen atom, a hydroxy group or an alkyl group of C 1 ~ C 4 .
이와 같은 본 발명을 더욱 상세히 설명하면 다음과 같다.Referring to the present invention in more detail as follows.
본 발명은 20 ~ 60 kHz의 고주파 음파를 이용하여 상압 및 수용액 조건하에서도 고수율로 페닐글리신 유도체를 라세미화하는 방법에 관한 것이다. 본 발명에 따른 제조공정에서는 첨부된 도1에 나타낸 바와 같이 통상의 반응기에 고주파 음파 반응기를 설치한다.The present invention relates to a method for the racemization of phenylglycine derivatives in high yield under atmospheric pressure and aqueous solution conditions using high frequency sound waves of 20 to 60 kHz. In the manufacturing process according to the present invention, a high frequency acoustic wave reactor is installed in a conventional reactor as shown in FIG.
본 발명에 따른 라세미화 과정을 보다 구체적으로 설명하면 다음과 같다.Referring to the racemization process according to the present invention in more detail as follows.
L- 또는 D-페닐글리신 유도체를 물을 용매로하여 20 ~ 60 kHz 바람직하기로는 20 ~ 50 kHz의 고주파 음파, 70 ~ 100℃의 온도, 그리고 상압 조건하에서 5 ~ 10 시간정도 반응시킨다. 라세미화 반응 조건에 있어서, 20 kHz미만의 음파가 적용되면 본 발명에서 기대하는 효과를 얻을 수 없고, 60 kHz 이상의 고주파 음파는 일반적인 초음파 발생장치로는 얻기 어렵다. 그리고 반응온도가 70℃ 미만이면 반응이 느려 상대적으로 반응시간이 길어지는 문제가 있고, 100℃를 초과하면 물의 비점을 초과하므로 용매로 사용된 물이 증발하는 문제가 있다.The L- or D-phenylglycine derivative is reacted with water as a solvent at 20 to 60 kHz, preferably at a high frequency sound of 20 to 50 kHz, at a temperature of 70 to 100 ° C, and for 5 to 10 hours at atmospheric pressure. In the racemization reaction condition, when a sound wave of less than 20 kHz is applied, the effect expected in the present invention cannot be obtained, and a high frequency sound wave of 60 kHz or more is difficult to obtain with a general ultrasonic generator. And if the reaction temperature is less than 70 ℃ the reaction is slow because the reaction time is relatively long, if it exceeds 100 ℃ there is a problem that the water used as a solvent evaporates because it exceeds the boiling point of water.
상기와 같은 라세미화 과정을 마친 반응액으로부터 라세미 혼합물을 수득하기 위해서는 통상의 분리 정제 방법 예를들면 결정화, 여과, 건조 등을 수행한다. 이들 분리 정제 방법에 있어서, 특히 바람직하기로는 결정화이다. 결정화에 의하면, 반응액을 0 ~ 5℃로 냉각하여 석출된 결정을 여과하여 회수한다.In order to obtain a racemic mixture from the reaction solution after the racemization process as described above, a conventional separation and purification method such as crystallization, filtration, drying and the like is performed. In these separation purification methods, crystallization is particularly preferable. According to crystallization, the reaction solution is cooled to 0 to 5 ° C, and the precipitated crystals are collected by filtration.
본 발명에 따른 라세미화 방법에 의해 생성된 라세믹 D,L-페닐글리신 유도체의 라세미화를 측정한 결과에 의하면, 선광도가 0.0으로서 정량적으로 반응이 진행됨을 알 수 있었다.As a result of measuring the racemization of the racemic D, L-phenylglycine derivative produced by the racemization method according to the present invention, it was found that the reaction proceeded quantitatively with an optical degree of 0.0.
또한, 본 발명에 따른 라세미화 방법에서는 반응에 초음파를 도입함으로써 반응온도와 압력을 현저히 줄이는 효과를 얻었다.In addition, in the racemization method according to the present invention, by introducing ultrasonic waves into the reaction, an effect of significantly reducing the reaction temperature and pressure was obtained.
이하 본 발명을 실시예에 의거하여 더욱 상세히 설명하는 바, 본 발명이 이에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.
실시예 1 :Example 1:
첨부된 도1에 도시한 바와 같이 100 ㎖ 플라스크를 고주파 음파 반응기에 설치한 후, L-페닐글리신(1.0 g)과 물(40 ㎖)을 넣은 후 95℃로 승온하였다. 20 ~ 50 kHz 및 100℃의 조건하에서 7시간동안 반응시킨 후, 반응액을 0℃로 천천히 냉각시키면 결정이 석출된다. 석출된 결정을 여과하고 건조하여 흰색의 라세믹 D,L-페닐글리신 0.76g(수율 76%)을 얻었으며, 라세미화는 광학활성도를 측정하는 선광도측정기를 사용하여 측정한 결과 선광도가 0.0 으로서 정량적으로 진행되었음을 쉽게 확인할 수 있었다.As shown in FIG. 1, a 100 ml flask was installed in a high frequency sonic reactor, and then L-phenylglycine (1.0 g) and water (40 ml) were added thereto, and the temperature was raised to 95 ° C. After reacting for 7 hours under the conditions of 20-50 kHz and 100 ° C, crystals are precipitated by slowly cooling the reaction solution to 0 ° C. The precipitated crystals were filtered and dried to obtain 0.76 g of white racemic D, L-phenylglycine (yield 76%). The racemization was measured using an optical photometer to measure optical activity. It was easy to confirm that the progress was quantitatively.
녹는점 : 290 ~ 291℃Melting Point: 290 ~ 291 ℃
1H-NMR(D2O+NaOD, ppm) : δ 7.4(m, 5H), 4.3(s, 1H) 1 H-NMR (D 2 O + NaOD, ppm): δ 7.4 (m, 5H), 4.3 (s, 1H)
실시예 2 :Example 2:
첨부된 도1에 도시한 바와 같이 100 ㎖ 플라스크를 고주파 음파 반응기에 설치한 후, L-파라-히드록시페닐글리신(2.0 g)과 물(50 ㎖)을 넣은 후 90℃로 승온 하였다. 20 ~ 50 kHz 및 90℃의 조건하에서 6시간동안 반응시킨 후, 반응액을 0℃로 천천히 냉각시키면 결정이 석출된다. 석출된 결정을 여과하고 건조하여 흰색의 라세믹 D,L-파라-히드록시페닐글리신 1.6g(수율 80%)을 얻었으며, 라세미화는 광학활성도를 측정하는 선광도측정기를 사용하여 측정한 결과 선광도가 0.0 으로서 정량적으로 진행되었음을 쉽게 확인할 수 있었다.As shown in FIG. 1, a 100 ml flask was installed in a high frequency sonic reactor, and then L-para-hydroxyphenylglycine (2.0 g) and water (50 ml) were added thereto, and the temperature was increased to 90 ° C. After reacting for 6 hours under the conditions of 20-50 kHz and 90 ° C, crystals are precipitated by slowly cooling the reaction solution to 0 ° C. The precipitated crystals were filtered and dried to obtain 1.6 g of white racemic D, L-para-hydroxyphenylglycine (yield 80%), and racemization was measured by using a photoluminometer to measure optical activity. It was easy to confirm that the fluorescence progressed quantitatively as 0.0.
녹는점 : 221℃ ~ 223℃Melting Point: 221 ℃ ~ 223 ℃
1H-NMR(D2O, ppm) : δ 7.2(d, 2H), 6.9(d, 2H), 4.7(s, 1H) 1 H-NMR (D 2 O, ppm): δ 7.2 (d, 2H), 6.9 (d, 2H), 4.7 (s, 1H)
비교예 1 :Comparative Example 1:
100㎖ 플라스크에 L-페닐글리신(1.0 g)과 물(40 ㎖)을 넣은 후, 95℃로 승온 하였다. 100℃에서 7시간동안 반응시킨 후, 반응액을 0℃로 천천히 냉각시키면 결정이 석출된다. 석출된 결정을 여과한후 건조하여 흰색의 페닐글리신 0.73g( 수율 73%)을 얻었으며, 라세미화는 4% 진행되었음을 선광도를 이용해서 쉽게 확인할 수 있었다.L-phenylglycine (1.0 g) and water (40 mL) were put into a 100 mL flask, and the temperature was raised to 95 ° C. After reacting at 100 ° C. for 7 hours, the reaction solution is slowly cooled to 0 ° C. to precipitate crystals. The precipitated crystals were filtered and dried to obtain 0.73 g of white phenylglycine (yield 73%), and racemization was easily confirmed by using the photoluminescence.
비교예 2 :Comparative Example 2:
100 ㎖ 플라스크에 L-파라-히드록시페닐글리신(2.0 g)과 물(50 ㎖)을 넣은 후, 90℃로 승온하였다. 90℃에서 6시간동안 반응시킨 후, 반응액을 0℃로 천천히 냉각시키면 결정이 석출된다. 석출된 결정을 여과한 후 건조하여 흰색의 라세믹 D,L-파라-히드록시페닐글리신 1.5g(수율 75%)을 얻었으며, 라세미화는 7% 진행진행되었음을 선광도를 이용해서 쉽게 확인할 수 있었다.L-para-hydroxyphenylglycine (2.0 g) and water (50 mL) were put into a 100 mL flask, and it heated up at 90 degreeC. After reacting at 90 ° C. for 6 hours, the reaction solution is slowly cooled to 0 ° C. to precipitate crystals. The precipitated crystals were filtered and dried to obtain 1.5 g (yield 75%) of white racemic D, L-para-hydroxyphenylglycine, and racemization was easily confirmed by using photoluminescence. there was.
상기 실시예와 비교예에서 보여주는 바와 같이, 반응온도와 반응시간을 동일하게 주었을 때 초음파의 적용 여부에 따라 라세미화 정도는 현저한 차이를 보였다. 즉, 일본공개특허 소48-67230호가 밀폐된 용기내에서 160℃의 고온조건으로 라세미화 반응을 수행하는데 반하여, 본 발명에 따른 제조방법은 상압 및 70 ~ 100℃의 비교적 온화한 반응조건하에서도 고수율로 라세믹 D,L-페닐글리신 유도체를 얻을 수 있다.As shown in the above Examples and Comparative Examples, given the same reaction temperature and reaction time, the degree of racemization was significantly different depending on the application of ultrasound. That is, while Japanese Laid-Open Patent Publication No. 48-67230 performs a racemization reaction at a high temperature condition of 160 ° C. in a sealed container, the production method according to the present invention has high pressure under normal pressure and relatively mild reaction conditions of 70-100 ° C. The yield of racemic D, L-phenylglycine derivatives can be obtained.
본 발명에 따른 초음파를 이용한 광학활성을 갖는 페닐글리신 유도체의 라세미화 방법은 유기용매를 전혀 사용하지 않고 물용매내에서 상압조건으로 수행함에도 불구하고 고수율로 목적을 얻을 수 있으므로 산업적으로 매우 유리하다.The racemization method of phenylglycine derivative having optical activity using ultrasonic waves according to the present invention is very industrially advantageous because it can be obtained with a high yield even though it is carried out at atmospheric pressure in a water solvent without using any organic solvent. .
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