JP2002241356A - Method for producing asymmetric copper complex crystal - Google Patents
Method for producing asymmetric copper complex crystalInfo
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- JP2002241356A JP2002241356A JP2001041390A JP2001041390A JP2002241356A JP 2002241356 A JP2002241356 A JP 2002241356A JP 2001041390 A JP2001041390 A JP 2001041390A JP 2001041390 A JP2001041390 A JP 2001041390A JP 2002241356 A JP2002241356 A JP 2002241356A
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- copper complex
- asymmetric
- copper
- atom
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Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、不斉銅錯体結晶の
製造方法に関する。[0001] The present invention relates to a method for producing an asymmetric copper complex crystal.
【０００２】[0002]
【従来の技術】例えば（Ｒ）−Ｎ−サリチリデン−２−
アミノ−１，１−ジ（２−イソプロポキシフェニル）−
１−プロパノールと酢酸銅(II)とを反応させて得られる
不斉銅錯体は、ジアゾ化反応の触媒として有用であるこ
とが知られており（特公昭５３−４３９５５号公報）、
その製造方法としては、（Ｒ）−Ｎ−サリチリデン−２
−アミノ−１，１−ジ（２−イソプロポキシフェニル）
−１−プロパノールと酢酸銅(II)とをエタノール中で反
応させる方法が知られている。しかしながら、該不斉銅
錯体を結晶として取得するためには、溶媒置換、中和、
濃縮、洗浄等の操作を繰り返す必要があり、必ずしも工
業的に有利とは言えず、多くの場合、結晶として取り出
すことなく、例えば錯体調製液をそのままジアゾ化反応
に用いていた。しかしながら、該錯体調製液を保存した
り、移送したりする場合には、物流コストや保存コスト
が比較的大きく、また保存スペース等の面でも不利が大
きいため、工業的な観点からは、結晶として取り扱うこ
とができる不斉銅錯体の開発が望まれていた。2. Description of the Related Art For example, (R) -N-salicylidene-2-
Amino-1,1-di (2-isopropoxyphenyl)-
It is known that an asymmetric copper complex obtained by reacting 1-propanol with copper (II) acetate is useful as a catalyst for a diazotization reaction (Japanese Patent Publication No. 53-43955).
The production method includes (R) -N-salicylidene-2
-Amino-1,1-di (2-isopropoxyphenyl)
A method of reacting -1-propanol with copper (II) acetate in ethanol is known. However, in order to obtain the asymmetric copper complex as crystals, solvent replacement, neutralization,
It is necessary to repeat operations such as concentration and washing, and this is not necessarily industrially advantageous. In many cases, for example, a complex preparation solution is used as it is in a diazotization reaction without being taken out as crystals. However, when the complex preparation is stored or transported, the distribution cost and storage cost are relatively large, and disadvantages are large in terms of storage space and the like. The development of an asymmetric copper complex that can be handled has been desired.
【０００３】[0003]
【発明が解決しようとする課題】このような状況の下、
本発明者らは、結晶で取得可能な不斉銅錯体について鋭
意検討したところ、サリチリデン部位の３位または５位
に、ニトロ基やハロゲン原子を有するサリチリデンアミ
ノアルコールと銅（II）化合物を有機溶媒中で混合し、
晶析処理することにより、煩雑な溶媒置換、濃縮、洗浄
等の操作を繰り返すことなく、不斉銅錯体結晶を収率よ
く得ることができることを見いだし、本発明に至った。SUMMARY OF THE INVENTION Under such circumstances,
The present inventors have conducted intensive studies on asymmetric copper complexes obtainable in crystals, and found that a salicylidene amino alcohol having a nitro group or a halogen atom at the 3- or 5-position of the salicylidene moiety and a copper (II) compound. Mix in organic solvent,
The present inventors have found that by carrying out the crystallization treatment, it is possible to obtain an asymmetric copper complex crystal at a high yield without repeating complicated operations such as solvent replacement, concentration, and washing, and have accomplished the present invention.
【０００４】[0004]
【課題を解決するための手段】すなわち本発明は、一般
式（１） （式中、Ｒ1およびＲ2はそれぞれ同一または相異なっ
て、アルキル基、アラルキル基またはアリール基を表わ
し、Ｘ1はニトロ基、塩素原子または水素原子を表わ
し、Ｘ1がニトロ基のとき、Ｘ2は水素原子を、Ｘ1が塩
素原子のとき、Ｘ2は塩素原子を、Ｘ1が水素原子のと
き、Ｘ2はフッ素原子を表わす。また、＊は不斉炭素原
子を表わす。）で示される光学活性なサリチリデンアミ
ノアルコール化合物と銅（II）化合物を有機溶媒中で反
応させた後、晶析処理を行うことを特徴とする不斉銅錯
体結晶の製造方法を提供するものである。That is, the present invention provides a compound represented by the following general formula (1): (Wherein R 1 and R 2 are the same or different and each represents an alkyl group, an aralkyl group or an aryl group, X 1 represents a nitro group, a chlorine atom or a hydrogen atom, and when X 1 is a nitro group, X 2 represents a hydrogen atom, X 1 represents a chlorine atom, X 2 represents a chlorine atom, and X 1 represents a hydrogen atom, X 2 represents a fluorine atom, and * represents an asymmetric carbon atom.) A method for producing an asymmetric copper complex crystal, which comprises reacting an optically active salicylideneamino alcohol compound represented by the formula (1) with a copper (II) compound in an organic solvent, and then performing a crystallization treatment. It is.
【０００５】[0005]
【発明の実施の形態】まず、一般式（１） （式中、Ｒ1およびＲ2はそれぞれ同一または相異なっ
て、低級アルキル基、アラルキル基またはアリール基を
表わす。ここで、低級アルキル基、アラルキル基または
アリール基は置換基を有していてもよい。Ｘ1はニトロ
基、塩素原子または水素原子を表わし、Ｘ1がニトロ基
のとき、Ｘ2は水素原子を、Ｘ1が塩素原子のとき、Ｘ2
は塩素原子を、Ｘ1が水素原子のとき、Ｘ2はフッ素原子
を表わす。また、＊は不斉炭素原子を表わす。）で示さ
れる光学活性なサリチリデンアミノアルコール化合物
（以下、サリチリデンアミノアルコール化合物（１）と
略記する。）について説明する。DESCRIPTION OF THE PREFERRED EMBODIMENTS First, general formula (1) (Wherein R 1 and R 2 are the same or different and each represents a lower alkyl group, an aralkyl group or an aryl group. Here, the lower alkyl group, the aralkyl group or the aryl group may have a substituent. X 1 represents a nitro group, a chlorine atom or a hydrogen atom, and when X 1 is a nitro group, X 2 is a hydrogen atom; when X 1 is a chlorine atom, X 2
Represents a chlorine atom, and when X 1 is a hydrogen atom, X 2 represents a fluorine atom. * Represents an asymmetric carbon atom. )) (Hereinafter, abbreviated as salicylideneamino alcohol compound (1)).
【０００６】サリチリデンアミノアルコール化合物
（１）の式中、＊は不斉炭素原子を表わし、Ｒ1および
Ｒ2はそれぞれ同一または相異なって、低級アルキル
基、アラルキル基またはアリール基を表わす。かかる低
級アルキル基、アラルキル基またはアリール基は置換基
を有していてもよい。In the formula of the salicylideneamino alcohol compound (1), * represents an asymmetric carbon atom, and R 1 and R 2 are the same or different and each represents a lower alkyl group, an aralkyl group or an aryl group. Such a lower alkyl group, aralkyl group or aryl group may have a substituent.
【０００７】低級アルキル基としては、例えばメチル
基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−
ブチル基、イソブチル基、ｔｅｒｔ−ブチル基等の炭素
数１〜４のアルキル基が挙げられ、アリール基として
は、例えばフェニル基等およびフェニル基等の芳香環
に、例えばアルキル基、アルコキシ基等の置換基が置換
した２−メトキシフェニル基、２−ｔｅｒｔ−ブトキシ
−５−ｔｅｒｔ−ブチルフェニル基、２−オクチルオキ
シ−５−ｔｅｒｔ−ブチルフェニル基等が挙げられる。
また、アラルキル基としては、例えば上記したアリール
基とアルキル基とから構成されるものが挙げられ、具体
的には、ベンジル基、２−メトキシベンジル基等が挙げ
られる。The lower alkyl group includes, for example, methyl, ethyl, n-propyl, isopropyl, n-
Examples thereof include an alkyl group having 1 to 4 carbon atoms such as a butyl group, an isobutyl group, and a tert-butyl group. Examples of the aryl group include a phenyl group and the like and an aromatic ring such as a phenyl group; Examples thereof include a 2-methoxyphenyl group, a 2-tert-butoxy-5-tert-butylphenyl group, and a 2-octyloxy-5-tert-butylphenyl group substituted with a substituent.
Examples of the aralkyl group include those composed of the above-described aryl group and alkyl group, and specific examples include a benzyl group and a 2-methoxybenzyl group.
【０００８】また、上記サリチリデンアミノアルコール
化合物（１）の式中、Ｘ1はニトロ基、塩素原子または
水素原子を表わし、Ｘ1がニトロ基のとき、Ｘ2は水素原
子を、Ｘ1が塩素原子のとき、Ｘ2は塩素原子を、Ｘ1が
水素原子のとき、Ｘ2はフッ素原子を表わす。[0008] In the formula of the salicylidene amino alcohol compound (1), X 1 is nitro group, a chlorine atom or a hydrogen atom, when X 1 is a nitro group, a X 2 is a hydrogen atom, X 1 When X is a chlorine atom, X 2 represents a chlorine atom, and when X 1 is a hydrogen atom, X 2 represents a fluorine atom.
【０００９】かかるサリチリデンアミノアルコール化合
物（１）としては、例えば光学活性なＮ−（５−ニトロ
サリチリデン）−２−アミノ−１，１−ジフェニル−１
−プロパノール、光学活性なＮ−（３，５−ジクロロサ
リチリデン）−２−アミノ−１，１−ジフェニル−１−
プロパノール、光学活性なＮ−（３−フルオロサリチリ
デン）−２−アミノ−１，１−ジフェニル−１−プロパ
ノール、光学活性なＮ−（５−ニトロサリチリデン）−
２−アミノ−１，１−ジ（２−メトキシフェニル）−１
−プロパノール、光学活性なＮ−（３，５−ジクロロサ
リチリデン）−２−アミノ−１，１−ジ（２−メトキシ
フェニル）−１−プロパノール、光学活性なＮ−（３−
フルオロサリチリデン）−２−アミノ−１，１−ジ（２
−メトキシフェニル）−１−プロパノール、Examples of the salicylidene amino alcohol compound (1) include, for example, optically active N- (5-nitrosalicylidene) -2-amino-1,1-diphenyl-1.
-Propanol, optically active N- (3,5-dichlorosalicylidene) -2-amino-1,1-diphenyl-1-
Propanol, optically active N- (3-fluorosalicylidene) -2-amino-1,1-diphenyl-1-propanol, optically active N- (5-nitrosalicylidene)-
2-amino-1,1-di (2-methoxyphenyl) -1
-Propanol, optically active N- (3,5-dichlorosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol, optically active N- (3-
(Fluorosalicylidene) -2-amino-1,1-di (2
-Methoxyphenyl) -1-propanol,
【００１０】光学活性なＮ−（５−ニトロサリチリデ
ン）−２−アミノ−１，１−ジ（５−ｔｅｒｔ−ブチル
−２−ｔｅｒｔ−ブトキシフェニル）−３−フェニル−
１−プロパノール、光学活性なＮ−（３，５−ジクロロ
サリチリデン）−２−アミノ−１，１−ジ（５−ｔｅｒ
ｔ−ブチル−２−ｔｅｒｔ−ブトキシフェニル）−３−
フェニル−１−プロパノール、光学活性なＮ−（３−フ
ルオロサリチリデン）−２−アミノ−１，１−ジ（５−
ｔｅｒｔ−ブチル−２−ｔｅｒｔ−ブトキシフェニル）
−３−フェニル−１−プロパノール、光学活性なＮ−
（５−ニトロサリチリデン）−２−アミノ−１，１−ジ
（５−ｔｅｒｔ−ブチル−２−オクチルオキシフェニ
ル）−１−プロパノール、光学活性なＮ−（３，５−ジ
クロロサリチリデン）−２−アミノ−１，１−ジ（５−
ｔｅｒｔ−ブチル−２−オクチルオキシフェニル）−１
−プロパノール、光学活性なＮ−（３−フルオロサリチ
リデン）−２−アミノ−１，１−ジ（５−ｔｅｒｔ−ブ
チル−２−オクチルオキシフェニル）−１−プロパノー
ル等が挙げられる。かかるサリチリデンアミノアルコー
ル化合物（１）には、Ｒ体およびＳ体の光学活性体があ
るが、本発明にはそのどちらを用いてもよい。Optically active N- (5-nitrosalicylidene) -2-amino-1,1-di (5-tert-butyl-2-tert-butoxyphenyl) -3-phenyl-
1-propanol, optically active N- (3,5-dichlorosalicylidene) -2-amino-1,1-di (5-ter
t-butyl-2-tert-butoxyphenyl) -3-
Phenyl-1-propanol, optically active N- (3-fluorosalicylidene) -2-amino-1,1-di (5-
tert-butyl-2-tert-butoxyphenyl)
-3-phenyl-1-propanol, optically active N-
(5-nitrosalicylidene) -2-amino-1,1-di (5-tert-butyl-2-octyloxyphenyl) -1-propanol, optically active N- (3,5-dichlorosalicylidene) ) -2-Amino-1,1-di (5-
tert-butyl-2-octyloxyphenyl) -1
-Propanol, optically active N- (3-fluorosalicylidene) -2-amino-1,1-di (5-tert-butyl-2-octyloxyphenyl) -1-propanol and the like. The salicylideneamino alcohol compound (1) includes an R-form and an S-form optically active compound, and either of them may be used in the present invention.
【００１１】なお、かかるサリチリデンアミノアルコー
ル化合物（１）は、例えば一般式（２） で示される光学活性なアミノアルコール類（以下、アミ
ノアルコール類（２）と略記する。）と一般式（３） （式中、Ｘ1およびＸ2は前記と同じ意味を表す。）で示
されるサリチルアルデヒド誘導体（以下、サリチルアル
デヒド誘導体（３）と略記する。）とを反応させること
により製造することができる。The salicylidene amino alcohol compound (1) is, for example, represented by the general formula (2) And an optically active amino alcohol (hereinafter abbreviated as amino alcohol (2)) represented by the general formula (3). (Wherein X 1 and X 2 have the same meanings as described above) (hereinafter abbreviated as salicylaldehyde derivative (3)).
【００１２】アミノアルコール類（２）としては、例え
ば光学活性な２−アミノ−１，１−ジフェニル−１−プ
ロパノール、光学活性な２−アミノ−１，１−ジ（２−
メトキシフェニル）−１−プロパノール、光学活性な２
−アミノ−１，１−ジ（５−ｔｅｒｔ−ブチル−２−ｔ
ｅｒｔ−ブトキシフェニル）−３−フェニル−１−プロ
パノール、光学活性な２−アミノ−１，１−ジ（５−ｔ
ｅｒｔ−ブチル−２−オクチルオキシフェニル）−１−
プロパノール等が挙げられる。かかるアミノアルコール
類（２）には、Ｒ体およびＳ体の２種類の光学活性体が
あるが、目的とするサリチリデンアミノアルコール化合
物（１）に応じて適宜選択すればよい。Examples of the amino alcohols (2) include optically active 2-amino-1,1-diphenyl-1-propanol and optically active 2-amino-1,1-di (2-
Methoxyphenyl) -1-propanol, optically active 2
-Amino-1,1-di (5-tert-butyl-2-t
ert-butoxyphenyl) -3-phenyl-1-propanol, optically active 2-amino-1,1-di (5-t
tert-butyl-2-octyloxyphenyl) -1-
And propanol. The amino alcohols (2) include two types of optically active isomers, R-form and S-form, which may be appropriately selected according to the target salicylidene amino alcohol compound (1).
【００１３】また、サリチルアルデヒド誘導体（３）と
しては、例えば２−ヒドロキシ−５−ニトロベンズアル
デヒド、２−ヒドロキシ−３，５−ジクロロベンズアル
デヒド、２−ヒドロキシ−３−フルオロベンズアルデヒ
ド等が挙げられる。その使用量は、アミノアルコール類
（２）に対して、通常１〜２モル倍、好ましくは１〜
１．５モル倍である。Examples of the salicylaldehyde derivative (3) include, for example, 2-hydroxy-5-nitrobenzaldehyde, 2-hydroxy-3,5-dichlorobenzaldehyde, 2-hydroxy-3-fluorobenzaldehyde and the like. The amount of use is usually 1 to 2 moles, preferably 1 to 1 mole times the amino alcohols (2).
It is 1.5 mole times.
【００１４】アミノアルコール類（２）とサリチルアル
デヒド誘導体（３）との反応は、通常その両者を混合す
ればよく、反応温度は、通常２０〜１５０℃、好ましく
は５０〜１２０℃である。反応は、通常溶媒の存在下に
行われ、溶媒としては、例えばトルエン、キシレン、ベ
ンゼン等の芳香族炭化水素系溶媒、例えばクロルベンゼ
ン、クロロホルム、ジクロロエタン等のハロゲン化炭化
水素系溶媒、例えばメタノール、エタノール等のアルコ
ール系溶媒等が挙げられる。これら溶媒はそれぞれ単独
で用いてもよいし、２種以上を混合して用い手もよい。
また、その使用量は特に限定されるものではない。The reaction between the amino alcohol (2) and the salicylaldehyde derivative (3) may be usually performed by mixing the two, and the reaction temperature is usually 20 to 150 ° C., preferably 50 to 120 ° C. The reaction is usually performed in the presence of a solvent.Examples of the solvent include aromatic hydrocarbon solvents such as toluene, xylene, and benzene, such as chlorobenzene, chloroform, and halogenated hydrocarbon solvents such as dichloroethane, such as methanol. Examples include alcohol solvents such as ethanol. These solvents may be used alone or in combination of two or more.
Further, the amount of use is not particularly limited.
【００１５】アミノアルコール類（２）とサリチルアル
デヒド誘導体（３）との反応は、通常定量的に進行する
ため、得られた反応液からサリチリデンアミノアルコー
ル化合物（１）を取り出すことなく、銅（II）化合物と
の反応に用いてもよいし、該反応液から、濃縮、晶析等
の処理により、サリチリデンアミノアルコール化合物
（１）を取り出し用いてもよい。もちろん取り出したサ
リチリデンアミノアルコール化合物（１）は、再結晶等
の通常の精製手段により精製した後、用いてもよい。Since the reaction between the amino alcohols (2) and the salicylaldehyde derivative (3) usually proceeds quantitatively, the reaction is carried out without removing the salicylidene amino alcohol compound (1) from the obtained reaction solution. (II) The salicylidene amino alcohol compound (1) may be used in the reaction with the compound, or the salicylidene amino alcohol compound (1) may be taken out from the reaction solution by a treatment such as concentration or crystallization. Of course, the salicylideneamino alcohol compound (1) taken out may be used after being purified by ordinary purification means such as recrystallization.
【００１６】銅（II）化合物としては、例えば酢酸銅
（II）、トリフルオロメタンスルホン酸銅（II）、臭化
銅（II）、塩化銅（II）等の２価の銅化合物が挙げられ
る。これらは、それぞれ単独で用いてもよいし、２種以
上を混合して用いてもよい。Examples of the copper (II) compound include divalent copper compounds such as copper acetate (II), copper (II) trifluoromethanesulfonate, copper (II) bromide, and copper (II) chloride. These may be used alone or in combination of two or more.
【００１７】銅（II）化合物の使用量は、サリチリデン
アミノアルコール化合物（１）に対して、通常０．９〜
１．５モル倍であり、好ましくは０．９〜１．２モル倍
である。The amount of the copper (II) compound to be used is generally 0.9 to 0.9% based on the salicylidene amino alcohol compound (1).
It is 1.5 mole times, preferably 0.9 to 1.2 mole times.
【００１８】サリチリデンアミノアルコール化合物
（１）と銅（II）化合物との反応は、通常溶媒中で実施
される。溶媒としては、例えばトルエン、キシレン等の
芳香族炭化水素系溶媒、例えば酢酸メチル、酢酸エチル
等のエステル系溶媒、例えばメタノール、エタノール等
のアルコール系溶媒、例えばジクロロメタン、クロロホ
ルム、ジクロロエタン等のハロゲン化炭化水素系溶媒、
例えばヘキサン、ヘプタン等の脂肪族炭化水素系溶媒等
が挙げられる。また、反応で得られた不斉銅錯体を、プ
ロキラルなオレフィン類のジアゾ化反応の触媒として用
いる場合であって、該プロキラルなオレフィン類が液体
であるときは、該プロキラルなオレフィン類を溶媒とし
て用いてもよい。なお、溶媒の使用量は、特に制限され
ない。The reaction between the salicylideneamino alcohol compound (1) and the copper (II) compound is usually carried out in a solvent. Examples of the solvent include aromatic hydrocarbon solvents such as toluene and xylene; ester solvents such as methyl acetate and ethyl acetate; alcohol solvents such as methanol and ethanol; and halogenated carbon solvents such as dichloromethane, chloroform and dichloroethane. Hydrogen-based solvent,
Examples thereof include aliphatic hydrocarbon solvents such as hexane and heptane. Further, when the asymmetric copper complex obtained by the reaction is used as a catalyst for the diazotization reaction of prochiral olefins, and when the prochiral olefin is a liquid, the prochiral olefin is used as a solvent. It may be used. The amount of the solvent used is not particularly limited.
【００１９】反応温度は、通常２０〜１２０℃、好まし
くは２０〜１００℃である。The reaction temperature is usually from 20 to 120 ° C, preferably from 20 to 100 ° C.
【００２０】反応終了後、反応液を晶析処理することに
より、目的とする不斉銅錯体が結晶として析出してく
る。晶析処理としては、例えば反応液をそのままもしく
は濃縮処理した後、冷却する方法、不斉銅錯体を溶解し
にくい溶媒（貧溶媒）と反応液を混合する方法、この両
者を併用した、反応液と貧溶媒を混合し、冷却する方法
等が挙げられ、不斉銅錯体結晶の取得量の面で、反応液
と貧溶媒を混合する方法および反応液と貧溶媒を混合
し、冷却する方法が好ましい。After completion of the reaction, the target asymmetric copper complex is precipitated as crystals by subjecting the reaction solution to a crystallization treatment. As the crystallization treatment, for example, a method of cooling the reaction solution as it is or after a concentration treatment, a method of mixing the reaction solution with a solvent (poor solvent) that hardly dissolves the asymmetric copper complex, a reaction solution using both of them, And a method of mixing the poor solvent and cooling, and in terms of the amount of asymmetric copper complex crystals obtained, a method of mixing the reaction solution and the poor solvent and a method of mixing the reaction solution and the poor solvent and cooling. preferable.
【００２１】反応液を冷却する場合の冷却温度は、通常
−５０〜３０℃、好ましくは−１０〜２０℃である。The cooling temperature for cooling the reaction solution is usually -50 to 30 ° C, preferably -10 to 20 ° C.
【００２２】反応液と貧溶媒を混合する場合の貧溶媒と
しては、不斉銅錯体を溶解しにくい溶媒であれば特に限
定されないが、例えばヘキサン、ヘプタン等の脂肪族炭
化水素系溶媒が挙げられる。貧溶媒の使用量は、サリチ
リデンアミノアルコール化合物（１）と銅（II）化合物
との反応に用いた溶媒の種類や使用量に応じて、適宜設
定すればよい。なお、サリチリデンアミノアルコール化
合物（１）と銅（II）化合物との反応の溶媒として、貧
溶媒を用いた場合には、反応温度や溶媒の使用量等の反
応条件によっては、反応終了後に、反応液から不斉銅錯
体結晶が析出していることがあり、この場合には、析出
した不斉銅錯体結晶をそのまま取り出してもよい。When the reaction solution and the poor solvent are mixed, the poor solvent is not particularly limited as long as it is a solvent that does not easily dissolve the asymmetric copper complex, and examples thereof include aliphatic hydrocarbon solvents such as hexane and heptane. . The amount of the poor solvent used may be appropriately set according to the type and amount of the solvent used in the reaction between the salicylideneamino alcohol compound (1) and the copper (II) compound. When a poor solvent is used as a solvent for the reaction between the salicylideneamino alcohol compound (1) and the copper (II) compound, depending on the reaction conditions such as the reaction temperature and the amount of the solvent used, after the reaction is completed. In some cases, asymmetric copper complex crystals are precipitated from the reaction solution. In this case, the precipitated asymmetric copper complex crystals may be directly taken out.
【００２３】析出した不斉銅錯体結晶は、濾過性もよ
く、通常の濾過操作により容易に取り出すことができ
る。The precipitated asymmetric copper complex crystal has good filterability and can be easily taken out by a usual filtration operation.
【００２４】取り出した不斉銅錯体は、例えばプロキラ
ルなオレフィン類とジアゾ酢酸エステル類との反応にお
いて触媒活性を示す。The extracted asymmetric copper complex exhibits catalytic activity, for example, in the reaction of prochiral olefins with diazoacetic esters.
【００２５】[0025]
【実施例】以下、実施例により本発明をさらに詳細に説
明するが、本発明はこれら実施例に限定されるものでな
い。The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
【００２６】実施例１ （Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−アミノ
−１，１−ジ（２−メトキシフェニル）−１−プロパノ
ール１９．６ｇおよび酢酸銅（II）８．９６ｇをトルエ
ン１６０ｇ中で混合し、内温８０℃で１時間攪拌、保持
した。その後、反応液を内温１０℃に冷却したところ、
青緑色の結晶が析出した。該結晶を濾取し、冷トルエン
５０ｇで洗浄、さらに室温で乾燥させ、［（Ｒ）−Ｎ−
（５−ニトロサリチリデン）−２−アミノ−１，１−ジ
（２−メトキシフェニル）−１−プロパノール］銅錯体
１９．１ｇを得た。収率：８２．０％。Example 1 19.6 g of (R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol and copper (II) acetate 8 0.96 g was mixed in 160 g of toluene, and the mixture was stirred and maintained at an internal temperature of 80 ° C. for 1 hour. Then, when the reaction solution was cooled to an internal temperature of 10 ° C,
Blue-green crystals precipitated. The crystals were collected by filtration, washed with 50 g of cold toluene, further dried at room temperature, and [(R) -N-
(5-Nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol] copper complex was obtained in an amount of 19.1 g. Yield: 82.0%.
【００２７】実施例２ （Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−アミノ
−１，１−ジ（２−メトキシフェニル）−１−プロパノ
ール１９．６ｇおよび酢酸銅（II）８．９６ｇをトルエ
ン１００ｇ中で混合し、内温８０℃で１時間攪拌、保持
した。その後、同温度で、反応液にヘプタン１００ｇを
加えたところ、青緑色の結晶が析出した。さらに、結晶
が析出した反応懸濁液を、内温１０℃に冷却し、析出結
晶を濾取した。濾取した結晶を、ヘプタンで洗浄し、室
温で乾燥させ、［（Ｒ）−Ｎ−（５−ニトロサリチリデ
ン）−２−アミノ−１，１−ジ（２−メトキシフェニ
ル）−１−プロパノール］銅錯体２２．１ｇを得た。収
率：９９．０％。Example 2 19.6 g of (R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol and copper (II) acetate 8 0.96 g was mixed in 100 g of toluene, and the mixture was stirred and maintained at an internal temperature of 80 ° C. for 1 hour. Thereafter, 100 g of heptane was added to the reaction solution at the same temperature, and blue-green crystals were precipitated. Further, the reaction suspension in which the crystals were precipitated was cooled to an internal temperature of 10 ° C., and the precipitated crystals were collected by filtration. The collected crystals were washed with heptane, dried at room temperature, and [(R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-. [Propanol] copper complex (22.1 g) was obtained. Yield: 99.0%.
【００２８】実施例３ （Ｒ）−Ｎ−（３，５−ジクロロサリチリデン）−２−
アミノ−１，１−ジ（２−メトキシフェニル）−１−プ
ロパノール０．４２ｇおよび酢酸銅（II）０．１８ｇを
トルエン１０ｇ中で混合し、内温８０℃で１時間攪拌、
保持した。その後、同温度で、反応液にヘプタン１０ｇ
を加えたところ、青緑色の結晶が析出した。さらに、結
晶が析出した反応懸濁液を、内温１０℃に冷却し、析出
結晶を濾取した。濾取した結晶を、ヘプタンで洗浄し、
室温で乾燥させ、［（Ｒ）−Ｎ−（３，５−ジクロロサ
リチリデン）−２−アミノ−１，１−ジ（２−メトキシ
フェニル）−１−プロパノール］銅錯体０．４６ｇを得
た。収率：９７．９％。Example 3 (R) -N- (3,5-dichlorosalicylidene) -2-
A mixture of 0.42 g of amino-1,1-di (2-methoxyphenyl) -1-propanol and 0.18 g of copper (II) acetate in 10 g of toluene was stirred at an internal temperature of 80 ° C. for 1 hour.
Held. Thereafter, at the same temperature, 10 g of heptane was added to the reaction solution.
, Blue-green crystals were precipitated. Further, the reaction suspension in which the crystals were precipitated was cooled to an internal temperature of 10 ° C., and the precipitated crystals were collected by filtration. The filtered crystals are washed with heptane,
Dry at room temperature to obtain 0.46 g of [(R) -N- (3,5-dichlorosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol] copper complex. Was. Yield: 97.9%.
【００２９】実施例４ （Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−アミノ
−１，１−ジフェニル−１−プロパノール０．３８ｇお
よび酢酸銅（II）０．２０ｇをトルエン１０ｇ中で混合
し、内温８０℃で１時間攪拌、保持した。その後、銅温
度で、反応液にヘプタン１０ｇを加えたところ、青緑色
の結晶が析出した。さらに、結晶が析出した反応懸濁液
を、内温１０℃に冷却し、析出結晶を濾取した。濾取し
た結晶を、ヘプタンで洗浄し、室温で乾燥させ、
［（Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−アミ
ノ−１，１−ジフェニル−１−プロパノール］銅錯体
０．４３４ｇを得た。収率：９９．１％。Example 4 0.38 g of (R) -N- (5-nitrosalicylidene) -2-amino-1,1-diphenyl-1-propanol and 0.20 g of copper (II) acetate in 10 g of toluene And stirred and maintained at an internal temperature of 80 ° C. for 1 hour. Thereafter, 10 g of heptane was added to the reaction solution at a copper temperature, and blue-green crystals were precipitated. Further, the reaction suspension in which the crystals were precipitated was cooled to an internal temperature of 10 ° C., and the precipitated crystals were collected by filtration. The filtered crystals were washed with heptane and dried at room temperature,
0.434 g of [(R) -N- (5-nitrosalicylidene) -2-amino-1,1-diphenyl-1-propanol] copper complex was obtained. Yield: 99.1%.
【００３０】参考例１ 窒素置換した１００ｍＬシュレンク管に、２，５−ジメ
チル−２，４−ヘキサジエン３３．０６ｇおよび
［（Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−アミ
ノ−１，１−ジ（２−メトキシフェニル）−１−プロパ
ノール］銅錯体４．９７ｍｇを加え、フェニルヒドラジ
ン４ｍｇを添加した後、内温８０℃でジアゾ酢酸エチル
１．１４ｇを２時間かけて滴下した。滴下終了後、さら
に同温度で３０分攪拌、保持し、ガスクロマトグラフィ
ーにより分析すると、菊酸エチルエステルのジアゾ酢酸
エチルに対する収率は、９７．６％、トランス体／シス
体比＝５８／４２であった。液体クロマトグラフィーに
より光学純度を分析したところ、トランス体は６３％
ｅ．ｅ．、シス体は５７％ｅ．ｅ．であった。Reference Example 1 In a 100 mL Schlenk tube purged with nitrogen, 33.06 g of 2,5-dimethyl-2,4-hexadiene and [(R) -N- (5-nitrosalicylidene) -2-amino-1 were added. , 1-Di (2-methoxyphenyl) -1-propanol] copper complex, 4.97 mg of phenylhydrazine, and 1.14 g of ethyl diazoacetate were added dropwise at 80 ° C. over 2 hours. After the completion of the dropwise addition, the mixture was further stirred and maintained at the same temperature for 30 minutes and analyzed by gas chromatography. Met. Analysis of the optical purity by liquid chromatography revealed that the trans form was 63%
e. e. Cis-isomer is 57% e. e. Met.
【００３１】参考例２ 参考例１において、［（Ｒ）−Ｎ−（５−ニトロサリチ
リデン）−２−アミノ−１，１−ジ（２−メトキシフェ
ニル）−１−プロパノール］銅錯体の使用量を５．２２
ｍｇとした以外は、参考例１と同様に実施した。菊酸エ
チルエステルのジアゾ酢酸エチルに対する収率は９７．
６％、トランス体／シス体比＝６０／４０であった。ト
ランス体の光学純度は６１％ｅ．ｅ．、シス体の光学純
度は５６％ｅ．ｅ．であった。Reference Example 2 In Reference Example 1, the copper complex of [(R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol] copper was used. 5.22 usage
The procedure was performed in the same manner as in Reference Example 1 except that the amount was changed to mg. The yield of chrysanthemic acid ethyl ester with respect to ethyl diazoacetate was 97.
6%, trans / cis ratio = 60/40. The optical purity of the trans form is 61% e. e. And the optical purity of the cis isomer was 56% e. e. Met.
【００３２】実施例７ 参考例１において、［（Ｒ）−Ｎ−（５−ニトロサリチ
リデン）−２−アミノ−１，１−ジ（２−メトキシフェ
ニル）−１−プロパノール］銅錯体４．９７ｍｇに代え
て、［（Ｒ）−Ｎ−（５−ニトロサリチリデン）−２−
アミノ−１，１−ジフェニル−１−プロパノール］銅錯
体４．３８ｍｇを用いた以外は、参考例１と同様にして
実施した。菊酸エチルエステルのジアゾ酢酸エチルに対
する収率は９６．５％、トランス体／シス体比＝６１／
３９であった。トランス体の光学純度は５５％ｅ．
ｅ．、シス体の光学純度は４７％ｅ．ｅ．であった。Example 7 In Example 1, [(R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol] copper complex 4 [(R) -N- (5-nitrosalicylidene) -2-
[Amino-1,1-diphenyl-1-propanol] copper complex was used in the same manner as in Reference Example 1 except for using 4.38 mg of a copper complex. The yield of ethyl chrysanthemic acid based on ethyl diazoacetate was 96.5%, and the ratio of trans / cis isomers = 61 /
39. The optical purity of the trans form is 55% e.
e. The optical purity of the cis isomer was 47% e. e. Met.
【００３３】比較例１ （Ｒ）−Ｎ−サリチリデン−２−アミノ−１，１−ジフ
ェニル−１−プロパノール１．０ｇおよび酢酸銅（II）
０．５１ｇをトルエン５ｇ中で混合し、内温８０℃で１
時間攪拌、保持した後、ヘプタン５０ｇを加えたが、結
晶の析出は見られなかった。内温を１０℃まで冷却した
が、結晶は析出せず、均一な溶液のままであった。Comparative Example 1 1.0 g of (R) -N-salicylidene-2-amino-1,1-diphenyl-1-propanol and copper (II) acetate
0.51 g was mixed in 5 g of toluene,
After stirring and maintaining for an hour, 50 g of heptane was added, but no precipitation of crystals was observed. When the internal temperature was cooled to 10 ° C., no crystals were precipitated and the solution remained uniform.
【００３４】[0034]
【発明の効果】本発明によれば、光学活性なサリチリデ
ンアミノアルコール化合物のサリチリデン部位の３位ま
たは５位に、ニトロ基またはハロゲン原子を有するサリ
チリデンアミノアルコール化合物と、銅（II）化合物
を、有機溶媒中で反応させ、晶析処理することにより、
不斉銅錯体が結晶として容易に析出し、収率よく取り出
すことができる。ジアゾ化反応等の触媒として有用な不
斉銅錯体が、結晶として得ることができるため、例えば
保存、移送等の面で有利である。According to the present invention, a salicylidene aminoalcohol compound having a nitro group or a halogen atom at the 3- or 5-position of the salicylidene moiety of the optically active salicylideneaminoalcohol compound and copper (II) By reacting the compound in an organic solvent and subjecting it to crystallization,
The asymmetric copper complex is easily precipitated as a crystal and can be taken out in a good yield. Since an asymmetric copper complex useful as a catalyst for a diazotization reaction or the like can be obtained as crystals, it is advantageous in terms of, for example, storage and transfer.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 萩谷 弘寿 大阪府高槻市塚原２丁目10番１号 住友化 学工業株式会社内 Ｆターム(参考） 4H006 AA02 AC90 AD15 BB10 BB11 BB12 BB14 BB17 4H048 AA02 AC90 AD15 BB10 BB11 BB12 BB14 BB17 VA12 VA20 VA30 VA56 VB10 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Hirohisa Hagiya 2-10-1 Tsukahara, Takatsuki-shi, Osaka Sumitomo Chemical Co., Ltd. F-term (reference) 4H006 AA02 AC90 AD15 BB10 BB11 BB12 BB14 BB17 4H048 AA02 AC90 AD15 BB10 BB11 BB12 BB14 BB17 VA12 VA20 VA30 VA56 VB10
Claims (4)
て、低級アルキル基、アラルキル基またはアリール基を
表わす。ここで、低級アルキル基、アラルキル基または
アリール基は置換基を有していてもよい。Ｘ1はニトロ
基、塩素原子または水素原子を表わし、Ｘ1がニトロ基
のとき、Ｘ2は水素原子を、Ｘ1が塩素原子のとき、Ｘ2
は塩素原子を、Ｘ1が水素原子のとき、Ｘ2はフッ素原子
を表わす。また、＊は不斉炭素原子を表わす。）で示さ
れる光学活性なサリチリデンアミノアルコール化合物と
銅（II）化合物を有機溶媒中で反応させた後、晶析処理
を行うことを特徴とする不斉銅錯体結晶の製造方法。1. The general formula (1) (Wherein R 1 and R 2 are the same or different and each represents a lower alkyl group, an aralkyl group or an aryl group. Here, the lower alkyl group, the aralkyl group or the aryl group may have a substituent. X 1 represents a nitro group, a chlorine atom or a hydrogen atom, and when X 1 is a nitro group, X 2 is a hydrogen atom; when X 1 is a chlorine atom, X 2
Represents a chlorine atom, and when X 1 is a hydrogen atom, X 2 represents a fluorine atom. * Represents an asymmetric carbon atom. A) reacting an optically active salicylideneamino alcohol compound and a copper (II) compound in an organic solvent, and then subjecting the compound to a crystallization treatment.
記載の不斉銅錯体結晶の製造方法。2. The copper (II) compound is copper (II) acetate.
The method for producing an asymmetric copper complex crystal according to the above.
する請求項１に記載の不斉銅錯体結晶の製造方法。3. The method for producing an asymmetric copper complex crystal according to claim 1, wherein the reaction solution is cooled to crystallize the asymmetric copper complex crystal.
晶を晶析する請求項１に記載の不斉銅錯体結晶の製造方
法。4. The method for producing an asymmetric copper complex crystal according to claim 1, wherein a poor solvent is added to the reaction solution to crystallize the asymmetric copper complex crystal.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6852871B2 (en) * | 2002-06-12 | 2005-02-08 | Sumitomo Chemical Company Limited | Method for producing optically active salicylaldimine copper complex |
| WO2008050661A1 (en) | 2006-10-26 | 2008-05-02 | Sumitomo Chemical Company, Limited | Method for producing asymmetric copper complex crystal |
| JP2008133261A (en) * | 2006-10-26 | 2008-06-12 | Sumitomo Chemical Co Ltd | Process for producing asymmetric copper complex crystal |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5024254A (en) * | 1973-06-20 | 1975-03-15 | ||
| JPS5620521A (en) * | 1979-07-26 | 1981-02-26 | Sumitomo Chem Co Ltd | Separation of enantiomer mixture by using asymmetric copper complex through gas chromatography |
| JPH08217735A (en) * | 1995-02-16 | 1996-08-27 | Sumitomo Chem Co Ltd | Optically active schiff base and its production |
| JP2001278853A (en) * | 2000-01-25 | 2001-10-10 | Sumitomo Chem Co Ltd | Optically active copper complex, optically active salicylidene amino-alcohol compound and method for producing optically active cyclopropanecarboxylic acid derivative using the complex |
| JP2001278851A (en) * | 2000-01-25 | 2001-10-10 | Sumitomo Chem Co Ltd | Method for producing asymmetric copper complex and method for producing optically active cyclopropane compound using the same |
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2001
- 2001-02-19 JP JP2001041390A patent/JP4742428B2/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5024254A (en) * | 1973-06-20 | 1975-03-15 | ||
| JPS5620521A (en) * | 1979-07-26 | 1981-02-26 | Sumitomo Chem Co Ltd | Separation of enantiomer mixture by using asymmetric copper complex through gas chromatography |
| JPH08217735A (en) * | 1995-02-16 | 1996-08-27 | Sumitomo Chem Co Ltd | Optically active schiff base and its production |
| JP2001278853A (en) * | 2000-01-25 | 2001-10-10 | Sumitomo Chem Co Ltd | Optically active copper complex, optically active salicylidene amino-alcohol compound and method for producing optically active cyclopropanecarboxylic acid derivative using the complex |
| JP2001278851A (en) * | 2000-01-25 | 2001-10-10 | Sumitomo Chem Co Ltd | Method for producing asymmetric copper complex and method for producing optically active cyclopropane compound using the same |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6852871B2 (en) * | 2002-06-12 | 2005-02-08 | Sumitomo Chemical Company Limited | Method for producing optically active salicylaldimine copper complex |
| WO2008050661A1 (en) | 2006-10-26 | 2008-05-02 | Sumitomo Chemical Company, Limited | Method for producing asymmetric copper complex crystal |
| JP2008133261A (en) * | 2006-10-26 | 2008-06-12 | Sumitomo Chemical Co Ltd | Process for producing asymmetric copper complex crystal |
| US8153830B2 (en) | 2006-10-26 | 2012-04-10 | Sumitomo Chemical Company, Limited | Production method of asymmetric copper complex crystal |
| CN101528673B (en) * | 2006-10-26 | 2012-08-01 | 住友化学株式会社 | Method for producing asymmetric copper complex crystal |
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