JP3252579B2 - Racemization method for optically active 1- (halogenophenyl) ethylamines - Google Patents
Racemization method for optically active 1- (halogenophenyl) ethylaminesInfo
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- JP3252579B2 JP3252579B2 JP33544693A JP33544693A JP3252579B2 JP 3252579 B2 JP3252579 B2 JP 3252579B2 JP 33544693 A JP33544693 A JP 33544693A JP 33544693 A JP33544693 A JP 33544693A JP 3252579 B2 JP3252579 B2 JP 3252579B2
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- Japan
- Prior art keywords
- halogenophenyl
- optically active
- ethylamines
- ethylamine
- racemization
- Prior art date
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Description
【０００１】[0001]
【産業上の利用分野】本発明は、光学活性１−（ハロゲ
ノフェニル）エチルアミン類の新規ラセミ化法に関す
る。The present invention relates to a novel racemization method for optically active 1- (halogenophenyl) ethylamines.
【０００２】光学活性１−（ハロゲノフェニル）エチル
アミン類は、除草剤または殺菌剤のごとき農薬、あるい
は医薬中間原料として、また、塩基性光学分割剤として
有用である。[0002] Optically active 1- (halogenophenyl) ethylamines are useful as agricultural chemicals such as herbicides or fungicides, or as intermediates for pharmaceuticals, and as basic optical resolving agents.
【０００３】[0003]
【従来の技術】一般的に、光学活性１−（ハロゲノフェ
ニル）エチルアミン類はラセミ体で製造され、それらの
対掌体に光学分割される。たとえば、(1) （ＲＳ）−１
−（４−ハロゲノフェニル）エチルアミンをＬ−酒石酸
で光学分割する方法（Ｊｏｕｒｎａｌ ｏｆ Ｃｈｅｍ
ｉｃａｌ Ｓｏｃｉｅｔｙ（Ｂ），２４１８，（１９７
１））、(2) 光学活性テトラヒドロフラン−２−カルボ
ン酸で光学分割する方法（特開平１−２１６９６２号公
報）、(3) 光学活性Ｎ−ホルミルフェニルアラニンで光
学分割する方法（特開平２−３０６９４２号公報）、あ
るいは (4)光学活性酒石酸アニリド誘導体などで光学分
割する方法（特開平４−２６０４１８号公報）により、
容易に光学活性１−（ハロゲノフェニル）エチルアミン
類を得ることができる。2. Description of the Related Art Generally, optically active 1- (halogenophenyl) ethylamines are produced in a racemic form and optically resolved into their enantiomers. For example, (1) (RS) -1
Method of optically resolving-(4-halogenophenyl) ethylamine with L-tartaric acid (Journal of Chem)
Ical Society (B), 2418, (197
1)), (2) Optical resolution with optically active tetrahydrofuran-2-carboxylic acid (JP-A-1-216962), and (3) Optical resolution with optically active N-formylphenylalanine (JP-A-2-306942) JP-A-4-260418), or (4) a method of optical resolution with an optically active tartrate anilide derivative or the like (JP-A-4-260418).
Optically active 1- (halogenophenyl) ethylamines can be easily obtained.
【０００４】さらに、有用な光学対掌体を分離した後、
不用な対掌体をラセミ化し、そのラセミ体を再度光学対
掌体に分割する。これを繰り返すことができれば、工業
的に有利な光学活性体の製造法となる。従って、ラセミ
化は非常に重要な技術となる。Further, after separating useful optical antipodes,
The unwanted enantiomer is racemized and the racemate is again split into optical enantiomers. If this can be repeated, it will be an industrially advantageous method for producing an optically active substance. Therefore, racemization is a very important technique.
【０００５】光学活性１−（ハロゲノフェニル）エチル
アミン類のラセミ化方法としては、例えば、光学活性１
−（４−クロロフェニル）エチルアミンを適宜適当なア
ルコ−ル存在下にジメチルスルホキシド中で、金属アル
コキシド類と反応させる方法（特開平４−２７５２５８
号公報）などが知られている。As a method for racemizing optically active 1- (halogenophenyl) ethylamines, for example,
A method of reacting-(4-chlorophenyl) ethylamine with metal alkoxides in dimethyl sulfoxide in the presence of a suitable alcohol (JP-A-4-275258)
No. 1).
【０００６】[0006]
【発明が解決しようとする課題】しかし、上記ラセミ化
法は脱ハロゲン化が起こりやすく収率が十分でないこ
と、また沸点が高く、水と均一になるジメチルスルホキ
シドを溶媒として用いるために１−（ハロゲノフェニ
ル）エチルアミン類との分離が工業的規模での操作上難
しいなどの欠点を有している。However, the above-mentioned racemization method involves 1- () because dimethyl sulfoxide, which has a high boiling point and is uniform with water, is used as a solvent because the dehalogenation easily occurs and the yield is insufficient. (Halogenophenyl) ethylamines have disadvantages such as difficulty in operation on an industrial scale.
【０００７】[0007]
【課題を解決するための手段】そこで、本発明者らは、
光学活性１−（ハロゲノフェニル）エチルアミン類の工
業的に有利なラセミ化方法について鋭意検討した結果、
本発明に到達した。Means for Solving the Problems Accordingly, the present inventors have:
As a result of intensive studies on an industrially advantageous racemization method for optically active 1- (halogenophenyl) ethylamines,
The present invention has been reached.
【０００８】すなわち、本発明は、一般式（Ｉ）That is, the present invention provides a compound represented by the general formula (I)
【化２】 （式中、Ｘは塩素原子または臭素原子を表す。）で表さ
れる光学活性１−（ハロゲノフェニル）エチルアミン類
と一般式（ＩＩ）Embedded image (Wherein, X represents a chlorine atom or a bromine atom) and an optically active 1- (halogenophenyl) ethylamine represented by the general formula (II):
【化３】 （式中、Ｙは水素原子、塩素原子または臭素原子を表
す。）で表されるアセトフェノン類を脱水、濃縮した液
に、アルカリ金属アルコキシド存在下に加熱し、しかる
後加水分解することを特徴とする光学活性１−（ハロゲ
ノフェニル）エチルアミン類のラセミ化法である。Embedded image (Wherein, Y represents a hydrogen atom, a chlorine atom or a bromine atom). A solution obtained by dehydrating and concentrating acetophenones represented by the formula (1) is heated in the presence of an alkali metal alkoxide, and then hydrolyzed. Is a method of racemizing optically active 1- (halogenophenyl) ethylamines.
【０００９】すなわち、光学活性１−（ハロゲノフェニ
ル）エチルアミン類とアセトフェノン類を共沸脱水する
ことにより、式（ＩＩＩ）に示すようなイミンを作り、
その二重結合の移動により異性化させ、光学活性１−
（ハロゲノフェニル）エチルアミン類をラセミ化させる
ものである。That is, an optically active 1- (halogenophenyl) ethylamine and acetophenone are azeotropically dehydrated to produce an imine represented by the formula (III) ,
The isomerization is caused by the transfer of the double bond, and the optically active 1-
(Halogenophenyl) ethylamines are racemized.
【００１０】[0010]
【化１】 二重結合の異性化により、Ａ，Ｂ２種のイミンが生成す
る。式中、ＸとＹが、同じで置換位置も同じであれば、
Ａ，Ｂは同種となり、イミンを加水分解することによ
り、どちらからも目的のラセミ化した１−（ハロゲノフ
ェニル）エチルアミン類とハロゲノアセトフェノン類が
生成する。式中、ＸとＹが異なった場合、ＸとＹが同じ
でもその置換位置が異なった場合はＡ，Ｂは異種のイミ
ンとなる。Ａのイミンを加水分解すると、目的のラセミ
化した１−（ハロゲノフェニル）エチルアミン類とアセ
トフェノン類が、Ｂのイミンを加水分解すれば、Ｙ置換
アセトフェノン類に由来する１−フェニルエチルアミン
類とハロゲノアセトフェノン類が生成する。ここで、副
生した１−フェニルエチルアミンとアセトフェノン、ハ
ロゲノアセトフェノン類は回収してリサイクルが可能で
ある。Embedded image By isomerization of the double bond, two kinds of imines A and B are formed. In the formula, if X and Y are the same and the substitution position is the same,
A and B become the same species, and the desired racemized 1- (halogenophenyl) ethylamines and halogenoacetophenones are produced from both by hydrolyzing the imine. In the formula, when X and Y are different, and when X and Y are the same but their substitution positions are different, A and B are different imines. When the imine of A is hydrolyzed, the target racemized 1- (halogenophenyl) ethylamines and acetophenones are obtained. When the imine of B is hydrolyzed, the 1-phenylethylamines derived from Y-substituted acetophenones and halogenoacetophenone are obtained. Kind is generated. Here, by-produced 1-phenylethylamine, acetophenone, and halogenoacetophenones can be collected and recycled.
【００１１】以下、本発明の構成を詳細に説明する。Hereinafter, the configuration of the present invention will be described in detail.
【００１２】本発明において適用される光学活性１−
（ハロゲノフェニル）エチルアミン類は１−（２−クロ
ロフェニル）エチルアミン、１−（３−クロロフェニ
ル）エチルアミン、１−（４−クロロフェニル）エチル
アミン、１−（２−ブロモフェニル）エチルアミン、１
−（３−ブロモフェニル）エチルアミン、１−（４−ブ
ロモフェニル）エチルアミンなどが挙げられる。Optical activity 1 used in the present invention
(Halogenophenyl) ethylamines include 1- (2-chlorophenyl) ethylamine, 1- (3-chlorophenyl) ethylamine, 1- (4-chlorophenyl) ethylamine, 1- (2-bromophenyl) ethylamine,
-(3-bromophenyl) ethylamine, 1- (4-bromophenyl) ethylamine and the like.
【００１３】本発明でラセミ化に使用される光学活性１
−（ハロゲノフェニル）エチルアミン類は、Ｒ体、Ｓ
体、あるいはこれらのうち１つの光学異性体を等量以上
含むものも使用することができる。Optical activity 1 used for racemization in the present invention
-(Halogenophenyl) ethylamines are R-form, S-form
It is also possible to use isomers or those containing one or more of these optical isomers in equal amounts or more.
【００１４】アルカリ金属アルコキシドとしては１〜６
の炭素数を有するアルカリ金属アルコキシドが好まし
く、具体的にはカリウムエトキシド、イソプロポキシ
ド、ｓｅｃ−ブトキシド、ｔｅｒｔ−ブトキシド、ｓｅ
ｃ−ペントキシド、ｔｅｒｔ−ペントキシドである。そ
の使用量は、光学活性１−（ハロゲノフェニル）エチル
アミン類１モルに対し、０．０１〜５モル、好ましくは
０．０５〜１．０モルである。As the alkali metal alkoxide, 1 to 6
Preferred are alkali metal alkoxides having the carbon number of, specifically, potassium ethoxide, isopropoxide, sec-butoxide, tert-butoxide,
c-pentoxide, tert-pentoxide. The amount used is 0.01 to 5 mol, preferably 0.05 to 1.0 mol, per 1 mol of the optically active 1- (halogenophenyl) ethylamines.
【００１５】本発明のラセミ化は、光学活性１−（ハロ
ゲノフェニル）エチルアミン類と前記一般式（ＩＩ）で
表されるアセトフェノン類を脱水してイミンを生成せし
め、この反応液を濃縮した後、アルカリ金属アルコキシ
ド存在下に加熱し、しかる後加水分解することによって
実施できる。The racemization of the present invention is carried out by optically active 1- (halogenophenyl) ethylamine and the above-mentioned formula (II).
The reaction can be carried out by dehydrating the acetophenone represented to produce an imine, concentrating the reaction solution, heating in the presence of an alkali metal alkoxide, and then hydrolyzing.
【００１６】光学活性１−（ハロゲノフェニル）エチル
アミン類と前記一般式（ＩＩ）で表されるアセトフェノ
ン類との脱水は、共沸脱水など、常法によって容易に進
行し、イミンが生成する。The dehydration of the optically active 1- (halogenophenyl) ethylamines and the acetophenones represented by the general formula (II) easily proceeds by a conventional method such as azeotropic dehydration. Is generated.
【００１７】本発明法におけるラセミ化反応は無溶媒、
溶媒存在下でも実施できるが、イミンの濃度が高い方が
イミンの二重結合の移動、すなわちラセミ化速度が速
い。使用可能な溶媒は光学活性１−（ハロゲノフェニ
ル）エチルアミン類、生成したイミンを変質せしめるこ
となく、かつラセミ化反応を妨害しないものであれば何
でも良く、ベンゼン、トルエンなどの芳香族系、ジオキ
サン、ジエチレングリコ−ルジメチルエ−テル等のエ−
テル系、２−プロパノ−ル、ｔｅｒｔ−ブタノ−ル等の
アルコ−ル系溶媒、あるいは、ヘキサン、シクロヘキサ
ンなどの脂肪族炭化水素系溶媒を用いることができる。In the method of the present invention, the racemization reaction is carried out without solvent.
Although it can be carried out in the presence of a solvent, the higher the concentration of imine, the faster the transfer of the double bond of imine, that is, the faster the racemization rate. The solvent which can be used is not particularly limited as long as it does not alter the optically active 1- (halogenophenyl) ethylamines or the imine formed and does not interfere with the racemization reaction, and aromatic solvents such as benzene and toluene, dioxane, and the like. Ethers such as diethylene glycol dimethyl ether;
Alcohol solvents such as ter, 2-propanol and tert-butanol, or aliphatic hydrocarbon solvents such as hexane and cyclohexane can be used.
【００１８】前記一般式（ＩＩ）で表されるアセトフェ
ノン類の使用量は、式（Ｉ）の光学活性１−（ハロゲノ
フェニル）エチルアミン類１モルに対して、０．２〜
２．０モル、好ましくは０．５〜１．５モルである。The amount of the acetophenone represented by the general formula (II) is from 0.2 to 1 mol of the optically active 1- (halogenophenyl) ethylamine of the formula (I).
2.0 mol, preferably 0.5 to 1.5 mol.
【００１９】ラセミ化反応は、通常温度５０〜２００
℃、好ましくは７０〜１５０℃で行われ、通常常圧で実
施されるが、微加圧、微減圧下においても実施可能であ
る。The racemization reaction is usually carried out at a temperature of 50 to 200.
C., preferably 70-150.degree. C., and is usually carried out at normal pressure, but can also be carried out under slight pressurization or slight pressure reduction.
【００２０】ラセミ化後イミンの加水分解は、常法によ
り容易に進行し、１−（ハロゲノフェニル）エチルアミ
ン類、１−フェニルエチルアミン、ハロゲノアセトフェ
ノン類、アセトフェノンが生成する。After the racemization, the hydrolysis of the imine proceeds easily by a conventional method to produce 1- (halogenophenyl) ethylamines, 1-phenylethylamine, halogenoacetophenones and acetophenone.
【００２１】本発明方法の好ましい実施態様では、光学
活性１−（ハロゲノフェニル）エチルアミン類を前記一
般式（ＩＩ）で表されるアセトフェノン類と、微量の塩
化亜鉛触媒とともにトルエン溶媒中デイーン・スターク
で共沸脱水した後濃縮し、その濃縮液にアルカリ金属ア
ルコキシドを添加して通常５０〜２００℃で加熱処理す
る。処理後希硫酸などの酸水溶液を加えて加水分解す
る。この反応混合物はアセトフェノン、ハロゲノアセト
フェノン類をトルエン等の有機溶媒で抽出した後、水層
を苛性ソ−ダなどの塩基の水溶液でアルカリ性とし、ト
ルエン等の有機溶媒で目的とするラセミ化された１−
（ハロゲノフェニル）エチルアミン類、１−フェニルエ
チルアミンを抽出する。抽出液を濃縮、必要に応じて蒸
留することにより１−（ハロゲノフェニル）エチルアミ
ン類を得ることができ、光学分割工程にもどすことがで
きる。１−（ハロゲノフェニル）エチルアミン類と共沸
脱水したアセトフェノン類に由来する１−フェニルエチ
ルアミン類は蒸留によって容易に除去できる。さらに回
収したアセトフェノン類は繰り返し使用が可能である。In a preferred embodiment of the method of the present invention, the optically active 1- (halogenophenyl) ethylamine is used for the above-mentioned one-method.
An acetophenone represented by the general formula (II) and a small amount of a zinc chloride catalyst are azeotropically dehydrated with Dean-Stark in a toluene solvent, and then concentrated. An alkali metal alkoxide is added to the concentrated solution, usually at 50 to 200 ° C. Heat treatment. After the treatment, an aqueous acid solution such as dilute sulfuric acid is added for hydrolysis. This reaction mixture was prepared by extracting acetophenone and halogenoacetophenones with an organic solvent such as toluene, and then making the aqueous layer alkaline with an aqueous solution of a base such as caustic soda. −
Extract (halogenophenyl) ethylamines and 1-phenylethylamine. The extract is concentrated and, if necessary, distilled to obtain 1- (halogenophenyl) ethylamines, which can be returned to the optical resolution step. 1-phenylethylamines derived from acetophenones azeotropically dehydrated with 1- (halogenophenyl) ethylamines can be easily removed by distillation. Further, the recovered acetophenones can be used repeatedly.
【００２２】[0022]
【実施例】以下、実施例により、本発明を説明するが、
本発明はこれらの実施例により限定されるものではな
い。Hereinafter, the present invention will be described with reference to examples.
The present invention is not limited by these examples.
【００２３】なお、実施例中の１−（ハロゲノフェニ
ル）エチルアミンのラセミ化に伴う光学純度（％ｅｅ）
の変化は、アミンとジ−ｐ−トルオイル−Ｌ−酒石酸無
水物（Ｌ−ＰＴＡＮ）と反応させた後、高速液体クロマ
トグラフィー（ＨＰＬＣ）により次の条件下で分析を行
った。The optical purity (% ee) accompanying the racemization of 1- (halogenophenyl) ethylamine in the examples.
Was analyzed by reacting the amine with di-p-toluoyl-L-tartaric anhydride (L-PTAN) and then performing high performance liquid chromatography (HPLC) under the following conditions.
【００２４】カラム：ＣＡＰＣＥＬＬ ＰＡＫ ＳＧ１
２０（資生堂）４．６mmφ×１５０mm 溶離液：０．０５％リン酸／メタノール＝３５／６５ 流速：１．０ml／min 検出：ＵＶ ２５４nm 保持時間：（Ｒ）−１−（４−クロロフェニル）エチル
アミンとＬ−ＰＴＡＮとの反応物１５．８分、（Ｓ）−
１−（４−クロロフェニル）エチルアミンとＬ−ＰＴＡ
Ｎとの反応物１９．０分。Column: CAPCELL PAK SG1
20 (Shiseido) 4.6 mmφ × 150 mm Eluent: 0.05% phosphoric acid / methanol = 35/65 Flow rate: 1.0 ml / min Detection: UV 254 nm Retention time: (R) -1- (4-chlorophenyl) ethylamine Reaction product of L-PTAN with 15.8 minutes, (S)-
1- (4-chlorophenyl) ethylamine and L-PTA
Reaction with N 19.0 min.
【００２５】ラセミ化率は次式によった。The racemization ratio was determined by the following equation.
【００２６】[0026]
【数１】 実施例１ 光学純度９６％ｅｅの（Ｒ）−１−（４−クロロフェニ
ル）エチルアミン１９．９ｇ（０．１２８モル）とアセ
トフェノン１５．７ｇ（０．１３０モル）、塩化亜鉛
０．３ｇおよびトルエン７０ｍｌを２００ｍｌフラスコ
に仕込み、デイーン・スタークを用いて８時間共沸脱水
した。エバポレーターで濃縮して濃縮液３７．７ｇを得
た。この濃縮液６．２ｇ（２１ミリモル）とカリウムｔ
ｅｒｔ−ブトキシド０．７５ｇ（７ミリモル）を冷却管
をつけた５０ｍｌ２口フラスコに仕込み、アルゴン気流
下１００℃で６時間加熱攪拌した。冷却後、２Ｎ硫酸１
７ｍｌを加えて１時間加熱還流して加水分解し、アセト
フェノン、４−クロロアセトフェノンをジクロロメタン
で抽出により除去した。水層に２Ｎ苛性ソーダ水溶液１
８ｍｌを添加し、ジクロロメタン１５ｍｌで２回抽出、
有機層を水洗、硫酸マグネシウムで乾燥した。ジクロロ
メタンを留去して蒸留することにより、沸点１０３℃／
１６ｔｏｒｒの１−（４−クロロフェニル）エチルアミ
ン１．０ｇ（６ミリモル）を得た。光学純度は７％ｅｅ
であり、ラセミ化率は９３％であった。なお、水層を硝
酸銀滴定したところクロル分解率は３．０モル％であっ
た。(Equation 1) Example 1 19.9 g (0.128 mol) of (R) -1- (4-chlorophenyl) ethylamine having an optical purity of 96% ee, 15.7 g (0.130 mol) of acetophenone , 0.3 g of zinc chloride and 70 ml of toluene Was charged into a 200 ml flask and azeotropically dehydrated for 8 hours using Dean-Stark. It was concentrated by an evaporator to obtain 37.7 g of a concentrate. 6.2 g (21 mmol) of this concentrate and potassium t
0.75 g (7 mmol) of tert-butoxide was charged into a 50 ml two-necked flask equipped with a condenser, and the mixture was heated and stirred at 100 ° C. for 6 hours under an argon stream. After cooling, 2N sulfuric acid 1
After adding 7 ml, the mixture was heated under reflux for 1 hour to hydrolyze, and acetophenone and 4-chloroacetophenone were removed by extraction with dichloromethane. 2N caustic soda aqueous solution 1
8 ml were added and extracted twice with 15 ml of dichloromethane,
The organic layer was washed with water and dried over magnesium sulfate. Dichloromethane is distilled off and distilled to give a boiling point of 103 ° C /
1.0 g (6 mmol) of 1- (4-chlorophenyl) ethylamine at 16 torr was obtained. Optical purity is 7% ee
And the racemization rate was 93%. When the aqueous layer was subjected to silver nitrate titration, the chlor decomposition rate was 3.0 mol%.
【００２７】実施例２ 実施例１の共沸脱水濃縮液５．１ｇ（１８ミリモル）と
カリウムｔｅｒｔ−ブトキシド１．１ｇ（１０ミリモ
ル）およびｔｅｒｔ−ブタノール２．０ｇを冷却管をつ
けた５０ｍｌ２口フラスコに仕込み、アルゴン気流下１
００℃で１０時間加熱攪拌した。冷却後、２Ｎ硫酸１５
ｍｌを加えて１時間加熱還流してＨＰＬＣ分析した結
果、１−（４−クロロフェニル）エチルアミンの光学純
度は１２％ｅｅ，ラセミ化率は８８％であった。硝酸銀
滴定によるクロル分解率は２．８モル％であった。Example 2 5.1 g (18 mmol) of the azeotropic dehydration concentrate of Example 1, 1.1 g (10 mmol) of potassium tert-butoxide and 2.0 g of tert-butanol were added to a 50 ml two-necked flask equipped with a condenser. And under argon flow 1
The mixture was heated and stirred at 00 ° C. for 10 hours. After cooling, 2N sulfuric acid 15
As a result of HPLC analysis by heating under reflux for 1 hour, the optical purity of 1- (4-chlorophenyl) ethylamine was 12% ee, and the racemization ratio was 88%. The chlorodecomposition by silver nitrate titration was 2.8 mol%.
【００２８】実施例３ 実施例１の共沸脱水濃縮液５．１ｇ（１８ミリモル）と
カリウムｔｅｒｔ−ブトキシド１．１ｇ（１０ミリモ
ル）およびｔｅｒｔ−ブタノ−ル５．１ｇを冷却管をつ
けた５０ｍｌ２口フラスコに仕込み、アルゴン気流下１
００℃で１４時間加熱攪拌した。冷却後、２Ｎ硫酸１６
ｍｌを加えて１時間加熱還流してＨＰＬＣ分析した結
果、１−（４−クロロフェニル）エチルアミンの光学純
度は１２％ｅｅ，ラセミ化率は８８％で，硝酸銀滴定に
よるクロル分解率は２．７モル％であった。Example 3 5.1 g (18 mmol) of the azeotropically dehydrated concentrated solution of Example 1, 1.1 g (10 mmol) of potassium tert-butoxide and 5.1 g of tert-butanol were added to a 50 ml tube equipped with a cooling tube. Charged into a neck flask and placed under an argon stream
The mixture was heated and stirred at 00 ° C. for 14 hours. After cooling, 2N sulfuric acid 16
As a result of HPLC analysis by heating under reflux for 1 hour, the optical purity of 1- (4-chlorophenyl) ethylamine was 12% ee, the racemization rate was 88%, and the chlorodecomposition rate by silver nitrate titration was 2.7 mol. %Met.
【００２９】実施例４ 実施例１の共沸脱水濃縮液７．０ｇ（２４ミリモル）と
カリウムｔｅｒｔ−ブトキシド１．３ｇ（１２ミリモ
ル）および１，４−ジオキサン７．０ｇを冷却管をつけ
た５０ｍｌ２口フラスコに仕込み、アルゴン気流下１２
０℃で６時間加熱攪拌した。冷却後、２Ｎ硫酸２０ｍｌ
を加えて１時間加熱還流してＨＰＬＣ分析した結果、１
−（４−クロロフェニル）エチルアミンの光学純度は２
３％ｅｅ，ラセミ化率は７６％であった。Example 4 7.0 g (24 mmol) of the azeotropically dehydrated concentrated solution of Example 1, 1.3 g (12 mmol) of potassium tert-butoxide and 7.0 g of 1,4-dioxane were added to a 50 ml tube equipped with a condenser. Charged into a flask, and placed under an argon stream.
The mixture was heated and stirred at 0 ° C. for 6 hours. After cooling, 2N sulfuric acid 20ml
Was added and heated under reflux for 1 hour.
The optical purity of-(4-chlorophenyl) ethylamine is 2
3% ee, racemization ratio was 76%.
【００３０】[0030]
【発明の効果】本発明によれば、光学分割の際に不用と
なる残りの光学活性１−（ハロゲノフェニル）エチルア
ミン類を工業的に実用化可能な手段でラセミ化でき、さ
らに光学分割を繰り返すことにより、収率よく、有用な
光学活性体に変換できる。According to the present invention, the remaining optically active 1- (halogenophenyl) ethylamines, which are unnecessary during optical resolution, can be racemized by means that can be industrially used, and the optical resolution is repeated. As a result, it can be converted into a useful optically active substance in good yield.
───────────────────────────────────────────────────── フロントページの続き (58)調査した分野(Int.Cl.7，ＤＢ名) C07C 211/29 C07B 55/00 C07C 209/68 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)────────────────────────────────────────────────── ─── Continued on the front page (58) Field surveyed (Int. Cl. 7 , DB name) C07C 211/29 C07B 55/00 C07C 209/68 CA (STN) REGISTRY (STN)
Claims (2)
ミン類と一般式（ＩＩ） 【化２】 （式中、Ｙは水素原子、塩素原子または臭素原子を表
す。） で表される アセトフェノン類を脱水、濃縮した後、アル
カリ金属アルコキシド存在下に加熱し、しかる後加水分
解することを特徴とする光学活性１−（ハロゲノフェニ
ル）エチルアミン類のラセミ化法。1. A compound of the general formula (I) (In the formula, X represents a chlorine atom or a bromine atom.) An optically active 1- (halogenophenyl) ethylamine represented by the general formula (II) : (In the formula, Y represents a hydrogen atom, a chlorine atom or a bromine atom.
You. A) dehydrating and concentrating the acetophenones represented by the formula (1), heating the mixture in the presence of an alkali metal alkoxide, and then hydrolyzing the acetophenones, followed by hydrolysis, whereby the optically active 1- (halogenophenyl) ethylamines are racemized.
ｓｅｃ−ブトキシドまたはカリウムｔｅｒｔ−ブトキシ
ドである光学活性１−（ハロゲノフェニル）エチルアミ
ン類のラセミ化法。2. A method for racemizing optically active 1- (halogenophenyl) ethylamines wherein the alkali metal alkoxide is potassium sec-butoxide or potassium tert-butoxide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33544693A JP3252579B2 (en) | 1993-12-28 | 1993-12-28 | Racemization method for optically active 1- (halogenophenyl) ethylamines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33544693A JP3252579B2 (en) | 1993-12-28 | 1993-12-28 | Racemization method for optically active 1- (halogenophenyl) ethylamines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH07188120A JPH07188120A (en) | 1995-07-25 |
| JP3252579B2 true JP3252579B2 (en) | 2002-02-04 |
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ID=18288655
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33544693A Expired - Fee Related JP3252579B2 (en) | 1993-12-28 | 1993-12-28 | Racemization method for optically active 1- (halogenophenyl) ethylamines |
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| Country | Link |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2172946C (en) * | 1995-03-30 | 2008-01-22 | Koji Hagiya | N-(.alpha.-alkylbenzylidene)-.alpha.-phenylalkylamine, its use and process for producing the same and process for producing intermediate |
| JP3843474B2 (en) * | 1995-12-07 | 2006-11-08 | 住友化学株式会社 | Method for racemizing optically active 1-phenylethylamine derivative |
| DE19606124A1 (en) * | 1996-02-20 | 1997-08-21 | Basf Ag | Process for the racemization of optically active amines |
| IN186804B (en) * | 1996-03-28 | 2001-11-10 | Nagase & Co Ltd | |
| DE19629692A1 (en) * | 1996-07-23 | 1998-01-29 | Bayer Ag | Process for the preparation of racemic phenethylamines |
| DE19905837A1 (en) * | 1999-02-12 | 2000-08-17 | Basf Ag | Process for the racemization of optically active amines |
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| Publication number | Publication date |
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