JPH051775B2 - - Google Patents
Info
- Publication number
- JPH051775B2 JPH051775B2 JP11457585A JP11457585A JPH051775B2 JP H051775 B2 JPH051775 B2 JP H051775B2 JP 11457585 A JP11457585 A JP 11457585A JP 11457585 A JP11457585 A JP 11457585A JP H051775 B2 JPH051775 B2 JP H051775B2
- Authority
- JP
- Japan
- Prior art keywords
- acid ester
- optically active
- distillation
- methyl
- present
- 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
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
（産業上の利用分野）
本発明は、光学活性α−クロルカルボン酸エス
テルをラセミ化を起さずに蒸留精製する方法に関
するものである。
（従来技術およびその問題点）
光学活性α−クロルカルボン酸エステル、例え
ば光学活性α−クロルプロピオン酸エステルは、
光学活性乳酸エステルと塩化チオニルから得られ
ることが既に知られているが、その精製工程にお
いてラセミ化が起り、所望の光学活性を有するも
のが得にくいという問題があつた。
特に、アミン類、アミド類等の塩基性化合物が
共存するときはラセミ化が起りやすく問題であつ
た。例えば特開昭56−7743には反応触媒としての
ピリジンの存在下、Ｄ−乳酸メチルと塩化チオニ
ルを反応させた後、蒸留することによつて光学活
性がほぼ保持されたまま目的とするＬ−２−クロ
ルプロピオン酸メチルが得られると記載されてい
る。しかしながら本発明者らが追試したところ蒸
留時間が長くなると得られるＬ−２−クロルプロ
ピオン酸メチルの光学純度が低下するという欠点
があることがわかつた。
フラスコスケールでは短時間で蒸留を終えるこ
とは可能であるが、工業的規模ではフラスコスケ
ール並の時間で蒸留を終えることは不可能であ
り、実用上問題があつた。
（問題を解決する為の手段）
本発明者らはこの欠点を改善すべく鋭意検討を
重ねた結果、精製蒸留時に不揮発性強酸を共存さ
せるとラセミ化が起こらないことを見出し本発明
に到達した。
即ち、本発明は、
式
(Industrial Application Field) The present invention relates to a method for distilling and purifying an optically active α-chlorocarboxylic acid ester without causing racemization. (Prior art and its problems) Optically active α-chlorocarboxylic acid ester, for example, optically active α-chloropropionic acid ester,
It is already known that it can be obtained from optically active lactic acid ester and thionyl chloride, but racemization occurs during the purification process, making it difficult to obtain a product with the desired optical activity. In particular, when basic compounds such as amines and amides coexist, racemization tends to occur, which is a problem. For example, in JP-A-56-7743, D-methyl lactate and thionyl chloride are reacted in the presence of pyridine as a reaction catalyst, and then distilled to obtain the desired L- It is stated that methyl 2-chloropropionate is obtained. However, when the present inventors conducted additional experiments, it was found that the optical purity of the obtained methyl L-2-chloropropionate decreases as the distillation time increases. Although it is possible to complete distillation in a short time on a flask scale, on an industrial scale it is impossible to complete distillation in the same amount of time as on a flask scale, which poses a practical problem. (Means for Solving the Problem) As a result of intensive studies to improve this drawback, the present inventors discovered that racemization does not occur when a non-volatile strong acid coexists during purification distillation, resulting in the present invention. . That is, the present invention has the following formula:
【式】
（式中R1，R2は炭素原子を１〜６個含むアル
キル基を表し、R1，R2は同一でも異つていても
よい）
で示される光学活性α−クロルカルボン酸エステ
ル粗製液を蒸留によつて精製するにあたり、不揮
発性強酸の存在下に蒸留することを特徴とする光
学活性α−クロルカルボン酸エステルの精製方法
である。
本発明の方法が最も有効に適用されるのは例え
ば、アミン類、アミド類等の塩基性化合物を触媒
として光学活性乳酸エステルと塩化チオニルから
光学活性２−クロルプロピオン酸エステルを製造
する場合の様に塩基性化合物が、光学活性α−ク
ロルカルボン酸エステル合成反応の触媒として使
用される場合である。
上記の場合、反応終了時点における粗製２−ク
ロルプロピオン酸エステル中にはSO2、HClが存
在していて塩基性化合物のラセミ化作用を抑制し
ているが、蒸留工程中にSO2、HClが系外に逃げ
て塩基性化合物がラセミ化触媒として作用し、後
の留分ほど光学純度が低下すると考えられる。
なお、α−クロルカルボン酸エステルの合成反
応に塩基性化合物を用いない場合でも本発明の方
法は適用できる。
本発明による方法では反応終了後に粗製α−ク
ロルカルボン酸エステルに硫酸、パラトルエンス
ルホン酸等の不揮発性強酸を添加してから精製蒸
留を行なう。添加する酸の量は反応触媒として用
いた塩基性化合物の１〜３当量程度で十分で、少
ないとラセミ化が抑制しきれず又多すぎるとター
ル化等が起こつて不利である。
（発明の効果）
不揮発性の強酸の存在下精製蒸留を行なうと光
学純度をほぼ保持したままで工業的にα−クロル
カルボン酸エステルが得られる。
以下、例を挙げて本発明を詳しく説明する。
実施例 １
塩化チオニルを200ｇ（1.65モル）をフラスコ
に仕込み、そこへＤ−乳酸メチル（〔α〕20 D＝＋
8.10゜）164ｇを室温で攪拌しながら滴下した。こ
のようにして粗製Ｄ−２−クロルスルフインオキ
シプロピオン酸メチルを得た。
滴下漏斗と二酸化硫黄吸収の為のアルカリ吸収
缶を備えたフラスコにピリジンを３ｇ入れ65℃に
加熱し、前述の粗製Ｄ−２−クロルスルフインオ
キシプロピオン酸メチルを約２時間かけて滴下し
た。滴下終了後２時間、65℃に保つてからH2
SO4を3.7ｇ添加し、50torrの減圧下で単蒸留を行
なつた。
約30分かけて83ｇのＬ−２−クロルプロピオン
酸メチルを留出させた後一旦単蒸留を中断した。
75℃で5Hr加熱後単蒸留を再開し、104ｇのＬ−
２−クロルプロピオン酸メチルを得た。
Ｄ−乳酸メチル基準の収率は96％で前半の留分
の比施光度は〔α〕20 D＝−26.54°、後半の留分の比
施光度は〔α〕20 D＝−26.45°であつた。
比較例 １
単蒸留を行なう前にH2SO4を添加しないこと
以外は実施例１と同様の操作を行なつた。
Ｌ−２−クロルプロピオン酸メチルの前半の留
分の比施光度は〔α〕20 D＝−25.59°、後半の留分の
比施光度は〔α〕20 D＝−20.03°であつた。
実施例 ２，３
塩基性触媒の種類、量及びH2SO4の添加量が
異なること以外は実施例１と同様の操作を行なつ
た。
結果は表に示した。
比較例 ２，３
H2SO4を添加しないこと以外は実施例２，３
と同様の操作を行なつた。結果は表に示した。[Formula] (In the formula, R 1 and R 2 represent an alkyl group containing 1 to 6 carbon atoms, and R 1 and R 2 may be the same or different.) Optically active α-chlorocarboxylic acid represented by This is a method for purifying an optically active α-chlorocarboxylic acid ester, which is characterized in that the crude ester liquid is purified by distillation in the presence of a nonvolatile strong acid. The method of the present invention is most effectively applied, for example, to the production of optically active 2-chloropropionic acid ester from optically active lactic acid ester and thionyl chloride using basic compounds such as amines and amides as catalysts. This is the case where a basic compound is used as a catalyst for the optically active α-chlorocarboxylic acid ester synthesis reaction. In the above case, SO 2 and HCl are present in the crude 2-chloropropionic acid ester at the end of the reaction and suppress the racemization effect of the basic compound, but SO 2 and HCl are present during the distillation process. It is thought that the basic compound that escapes from the system acts as a racemization catalyst, and that the optical purity of later fractions decreases. Note that the method of the present invention can be applied even when a basic compound is not used in the synthesis reaction of α-chlorocarboxylic acid ester. In the method according to the present invention, after the completion of the reaction, a strong non-volatile acid such as sulfuric acid or para-toluenesulfonic acid is added to the crude α-chlorocarboxylic acid ester, and then purification distillation is performed. The amount of acid added is sufficient to be about 1 to 3 equivalents of the basic compound used as a reaction catalyst; if it is too small, racemization cannot be suppressed, and if it is too large, tar formation may occur, which is disadvantageous. (Effects of the Invention) When purification distillation is carried out in the presence of a non-volatile strong acid, α-chlorocarboxylic acid ester can be obtained industrially while almost retaining its optical purity. Hereinafter, the present invention will be explained in detail by giving examples. Example 1 200 g (1.65 mol) of thionyl chloride was charged into a flask, and methyl D-lactate ([α] 20 D =+
8.10°) was added dropwise while stirring at room temperature. In this way, crude methyl D-2-chlorosulfinoxypropionate was obtained. 3 g of pyridine was placed in a flask equipped with a dropping funnel and an alkali canister for absorbing sulfur dioxide, heated to 65 DEG C., and the crude methyl D-2-chlorosulfinoxypropionate described above was added dropwise over about 2 hours. After dropping, keep at 65℃ for 2 hours and then add H2
3.7 g of SO 4 was added and simple distillation was performed under reduced pressure of 50 torr. After distilling off 83 g of methyl L-2-chloropropionate over about 30 minutes, the simple distillation was temporarily interrupted.
After heating at 75℃ for 5 hours, simple distillation was restarted and 104g of L-
Methyl 2-chloropropionate was obtained. The yield based on methyl D-lactate is 96%, the specific optical intensity of the first half fraction is [α] 20 D = -26.54°, and the specific optical intensity of the second half fraction is [α] 20 D = -26.45°. It was hot. Comparative Example 1 The same operation as in Example 1 was carried out except that H 2 SO 4 was not added before performing simple distillation. The specific optical power of the first half of the methyl L-2-chloropropionate fraction was [α] 20 D = -25.59°, and the specific optical power of the second half fraction was [α] 20 D = -20.03°. Examples 2 and 3 The same operations as in Example 1 were performed except that the type and amount of the basic catalyst and the amount of H 2 SO 4 added were different. The results are shown in the table. Comparative Example 2, 3 Example 2, 3 except that H 2 SO 4 was not added.
The same operation was performed. The results are shown in the table.
Claims (1)
キル基を表し、R1，R2は同一でも異つていても
よい） で示される光学活性α−クロルカルボン酸エステ
ル粗製液を蒸留によつて精製するにあたり、不揮
発性強酸の存在下に蒸留することを特徴とする光
学活性α−クロルカルボン酸エステルの精製方
法。[Claims] 1 Represented by the formula [Formula] (wherein R 1 and R 2 represent an alkyl group containing 1 to 6 carbon atoms, and R 1 and R 2 may be the same or different) A method for purifying an optically active α-chlorocarboxylic acid ester, which comprises distilling an optically active α-chlorocarboxylic acid ester crude liquid by distillation in the presence of a nonvolatile strong acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11457585A JPS61271249A (en) | 1985-05-28 | 1985-05-28 | Method of purifying optically-active alpha-chlorocarboxylic acid ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11457585A JPS61271249A (en) | 1985-05-28 | 1985-05-28 | Method of purifying optically-active alpha-chlorocarboxylic acid ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61271249A JPS61271249A (en) | 1986-12-01 |
| JPH051775B2 true JPH051775B2 (en) | 1993-01-11 |
Family
ID=14641268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP11457585A Granted JPS61271249A (en) | 1985-05-28 | 1985-05-28 | Method of purifying optically-active alpha-chlorocarboxylic acid ester |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61271249A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5326400B2 (en) | 2007-08-17 | 2013-10-30 | セントラル硝子株式会社 | Method for purifying optically active α-fluorocarboxylic acid ester |
-
1985
- 1985-05-28 JP JP11457585A patent/JPS61271249A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61271249A (en) | 1986-12-01 |
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