JPS63185943A - Racemization of optically active amine - Google Patents
Racemization of optically active amineInfo
- Publication number
- JPS63185943A JPS63185943A JP62016842A JP1684287A JPS63185943A JP S63185943 A JPS63185943 A JP S63185943A JP 62016842 A JP62016842 A JP 62016842A JP 1684287 A JP1684287 A JP 1684287A JP S63185943 A JPS63185943 A JP S63185943A
- Authority
- JP
- Japan
- Prior art keywords
- optically active
- methyl
- phenylpropylamine
- racemization
- reaction
- 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
- 230000006340 racemization Effects 0.000 title claims abstract description 19
- 150000001412 amines Chemical class 0.000 title abstract description 5
- WECUIGDEWBNQJJ-UHFFFAOYSA-N 4-phenylbutan-2-amine Chemical compound CC(N)CCC1=CC=CC=C1 WECUIGDEWBNQJJ-UHFFFAOYSA-N 0.000 claims abstract description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 238000010531 catalytic reduction reaction Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 abstract description 13
- 239000007868 Raney catalyst Substances 0.000 abstract description 7
- 229910017052 cobalt Inorganic materials 0.000 abstract description 7
- 239000010941 cobalt Substances 0.000 abstract description 7
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 abstract description 7
- 229910000564 Raney nickel Inorganic materials 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000007872 degassing Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WECUIGDEWBNQJJ-VIFPVBQESA-N (2s)-4-phenylbutan-2-amine Chemical compound C[C@H](N)CCC1=CC=CC=C1 WECUIGDEWBNQJJ-VIFPVBQESA-N 0.000 description 2
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- -1 Raney nickel Chemical compound 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- SYTBZMRGLBWNTM-SNVBAGLBSA-N (R)-flurbiprofen Chemical compound FC1=CC([C@H](C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-SNVBAGLBSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 235000001270 Allium sibiricum Nutrition 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- HZPNKQREYVVATQ-UHFFFAOYSA-L nickel(2+);diformate Chemical compound [Ni+2].[O-]C=O.[O-]C=O HZPNKQREYVVATQ-UHFFFAOYSA-L 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は光学活性１−メチル−３−フェニルプロピルア
ミン及びその酸付加塩の新規なラセミ化方法に関するも
のである。本発明法で得られるラセミ体の１−メチル−
３−フェニルプロピルアミンは例えば光学活性マンデル
酸ＣＲｅｃ１．Ｔｒａｖ。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel racemization method for optically active 1-methyl-3-phenylpropylamine and its acid addition salt. Racemic 1-methyl- obtained by the method of the present invention
3-phenylpropylamine is, for example, optically active mandelic acid CRec1. Trav.
Ｃｈｉｍ、Ｐａｙｓ−Ｂａｓ、８２．１８９（１９６Ｂ
）：１あるいは光学活性酒石酸（Ｃｏｌｌｅｃｔ、Ｃｚ
ｅｃｈ。Chim, Pays-Bas, 82.189 (196B
):1 or optically active tartaric acid (Collect, Cz
ech.
Ｃｈｅｍ、Ｏｏｍｍｕｎ、 ３３．３５５１（１９６８
）］により容易に光学分割され、光学活性１−メチル−
３−フェニルプロピルアミンへ導ひくことが出来る。光
学活性ｌ−メチル−３−フェニルプロピルアミン及びそ
の酸付加塩は医薬、農薬等の中間原料として有用な化合
物である。Chem, Oommun, 33.3551 (1968
)], and optically active 1-methyl-
This can lead to 3-phenylpropylamine. Optically active l-methyl-3-phenylpropylamine and its acid addition salts are useful compounds as intermediate raw materials for pharmaceuticals, agricultural chemicals, and the like.
光学活性１−メチル−３−フェニルプロピルアミンのラ
セミ化方法は知られていない。他の一般的アミンのラセ
ミ化法として、少なくとも１０バール（１０，１３気圧
）、望ましくは５０バール（５０，６５気圧）以上の水
素圧下で接触還元触媒を用いラセミ化する方法がドイツ
公開特許公報第２９０３５８９号において知られている
が、１０気圧より低圧下でのラセミ化方法は知られてい
ない。There is no known method for racemizing optically active 1-methyl-3-phenylpropylamine. Another common method for racemizing amines is a method of racemizing amines using a catalytic reduction catalyst under hydrogen pressure of at least 10 bar (10.13 atm), preferably 50 bar (50.65 atm) or more, as disclosed in the German Published Patent Application. No. 2,903,589, a racemization method under pressure lower than 10 atmospheres is not known.
光学活性１−メチルー３−フェニルプロピルアミンを製
造する主な方法は、ラセミ体１−メチルー３−フェニル
プロピルアミンの光学分割であシ、この光学分割によっ
て一方の有用な光学活性体が得られる。この際、不用と
なる光学対掌体をラセミ化することが出来れば、さらに
光学分割を繰シ返し行なうことにより有用な光学活性体
を収率良く取得でき、工業的に有利な製造法となる。ま
た、このラセミ化を１０気圧より低い圧力下で進行させ
ることが出来れば、簡易な耐圧反応釜中、高圧下に比べ
操作性よく、かつより安全にラセミ化反応を行なうこと
ができ、工業的に有利である。The main method for producing optically active 1-methyl-3-phenylpropylamine is the optical resolution of racemic 1-methyl-3-phenylpropylamine, which yields one useful optically active form. At this time, if the unnecessary optical antipode can be racemized, a useful optically active substance can be obtained in good yield by repeating optical resolution, making it an industrially advantageous production method. . Furthermore, if this racemization can proceed under a pressure lower than 10 atm, the racemization reaction can be carried out more easily and safely than in a simple pressure-resistant reactor under high pressure, and can be carried out industrially. It is advantageous for
〔問題点を解決するための手段及び作用効果〕本発明者
らは工業的に有利な光学活性１−メチル−３−フェニル
プロピルアミンの低圧下でのラセミ化方法を確立するこ
とを目的として鋭意研究を行った結果、本発明を完成し
た。即ち本発明は、光学活性１−メチル−８−フェニル
プロピルアミン及びその酸付加塩を水素圧１０気圧より
低圧下で接触還元触媒と共に加熱反応させることを特徴
とする光学活性１−メチル−３−フェニルプロピルアミ
ンのラセミ化方法である。以下に詳細説明する。[Means and effects for solving the problems] The present inventors have conducted extensive research with the aim of establishing an industrially advantageous method for racemizing optically active 1-methyl-3-phenylpropylamine under low pressure. As a result, the present invention was completed. That is, the present invention provides optically active 1-methyl-3-phenylpropylamine, which is characterized by heating and reacting optically active 1-methyl-8-phenylpropylamine and its acid addition salt together with a catalytic reduction catalyst under a hydrogen pressure lower than 10 atmospheres. This is a method for racemizing ruamine. The details will be explained below.
接触還元触媒としては、パラジウム炭素等の貴金属系触
媒、ラネーニッケル、ラネーコバルト、ラネー鉄、ラネ
ー銅等のラネー触媒、還元ニッケル、漆原ニッケル、ギ
酸ニッケル等のニッケル触媒をそれぞれ単独で使用する
か、また２種以上の混合物として使用するが、ラネーニ
ッケル、ラネーコバルトを用いるのが好ましい。これら
の触媒の使用量は光学活性１−メチル−３−フェニルプ
ロピルアミン１部に対し、０．０１〜０．５部が良い。As the catalytic reduction catalyst, a noble metal catalyst such as palladium carbon, a Raney catalyst such as Raney nickel, Raney cobalt, Raney iron, or Raney copper, a nickel catalyst such as reduced nickel, urushihara nickel, or formate nickel may be used alone, or A mixture of two or more of them is used, and Raney nickel and Raney cobalt are preferably used. The amount of these catalysts used is preferably 0.01 to 0.5 parts per 1 part of optically active 1-methyl-3-phenylpropylamine.
反応は無溶媒系でも実施できるが、ベンゼン。Although the reaction can be carried out in a solvent-free system, benzene is used.
トルエン、キシレン等芳香族系；エーテル、ＴＨＦ、ジ
オキサン等のエーテル系；ヘキサン、ヘプタン、シクロ
ヘキサン等の脂肪族炭化水素系の溶媒中で実施するのが
望ましい。反応は、温度５０〜２００℃、好ましくは１
２０〜１８０℃で行なわれ、使用水素圧は常圧から１０
気圧より低圧下で十分である。反応時間は反応温度等そ
の他の条件により適宜選択することができるが、一般的
に１〜２４時間で終了する。It is preferable to conduct the reaction in an aromatic solvent such as toluene or xylene; an ether solvent such as ether, THF or dioxane; or an aliphatic hydrocarbon solvent such as hexane, heptane or cyclohexane. The reaction is carried out at a temperature of 50 to 200°C, preferably 1
The temperature is 20 to 180℃, and the hydrogen pressure used is 10 to 10 degrees from normal pressure.
A pressure lower than atmospheric pressure is sufficient. Although the reaction time can be appropriately selected depending on other conditions such as reaction temperature, the reaction time is generally completed in 1 to 24 hours.
目的とするラセミ化された１−メチル−３−フェニルプ
ロピルアミンは、反応終了後、濾過、濃縮、蒸留又は塩
として再結晶等の公知の方法により容易に単離すること
ができる。After completion of the reaction, the desired racemized 1-methyl-3-phenylpropylamine can be easily isolated by known methods such as filtration, concentration, distillation, or recrystallization as a salt.
本発明に使用される光学活性１−メチル−３−フェニル
プロピルアミンは、光学活性すＲ体、８体あるいはいず
れかの光学純度がどの程度のものでも使用することがで
きる。ラセミ化反応に伴なう光学純度の変化は生成物の
旋光度を測定するか、生成物をモツシャー試薬により（
→−ＭＴＰＡアミド化〔ジャーナル・オブ・オーガニッ
ク・ケミズト ！Ｊ −（Ｊ、Ｏｒｇ、Ｃｈｅｍ、）
３４． ２５４８（１９６９）Ｉした後、日本分
光製ＦｉｎｅｐａｋＳＩＬ Ｃ，ｊ３カラム〔展開溶剤
メタノール／水＝１７１（容積比）〕によりジアステレ
オマー分析した結果えられる鏡像体過にＪ率（ｅ、 ｅ
、）より測定できる。The optically active 1-methyl-3-phenylpropylamine used in the present invention can be used regardless of the optical purity of the optically active R-form, 8-form, or either one. The change in optical purity accompanying the racemization reaction can be determined by measuring the optical rotation of the product, or by measuring the optical rotation of the product using a Motzscher reagent (
→-MTPA amidation [Journal of Organic Chemistry! J - (J, Org, Chem,)
34. 2548 (1969) I, diastereomer analysis was performed using a Finepak SIL C, j3 column manufactured by JASCO Corporation [developing solvent methanol/water = 171 (volume ratio)].
, ) can be measured.
つぎに実施例をあげて本発明をさらに詳しく説明するが
、本発明はかかる実施例のみに限定されるものではない
。Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited to these Examples.
実施例の収率およびラセミ化率は次のように定義する。The yield and racemization rate in Examples are defined as follows.
実施例１
５０ｍ１！のガラス製オートクレーブに（８） −１−
メチル−３−フェニルプロピルアミン５００ｍ、９（〔
α：］ ＝＋７．４８°（ｎｅａｔ）、６８％ｅ、
ｅ、 ）、ラネーニッケル５０ｍｇ、トルエン５ｍｌを
仕込み、減圧脱気後、水素圧７．５気圧、温度１５０℃
で２１時間反応した。反応終了後、冷却開封し、反応液
を濾過し触媒を除き、Ｆ液を濃縮し、淡黄色オイル４８
０ ｍ、！９を得た。得られたオイルをクーゲルロール
にて減圧下（１４ｍｍＨ，！ｉ＋） １０１〜１０２
℃で蒸留し、１−メチル−３−フェニルプロピルアミン
３８０ｍ、９（Ｃα：］、＝＋０．２８゜（ｎｅａｔ）
、 ２．１％ｅ、ｅ、 ）を得た。収率７６％、ラセ
ミ化率９７％。Example 1 50m1! (8) -1-
Methyl-3-phenylpropylamine 500m, 9 ([
α:] = +7.48° (neat), 68%e,
), 50 mg of Raney nickel, and 5 ml of toluene were charged, and after degassing under reduced pressure, the hydrogen pressure was 7.5 atm and the temperature was 150°C.
The reaction was carried out for 21 hours. After the reaction is completed, the package is cooled and opened, the reaction solution is filtered to remove the catalyst, and the F solution is concentrated.
0 m,! I got a 9. The obtained oil was heated under reduced pressure (14 mmH, !i+) using a Kugel roll. 101-102
Distilled at ℃ to give 1-methyl-3-phenylpropylamine 380m, 9(Cα:], = +0.28° (neat)
, 2.1% e, e, ) was obtained. Yield 76%, racemization rate 97%.
実施例２
５０ｍＪのガラス製オートクレーブに（旬−１−メチル
−３−フェニルプロピルアミンｌ（Ｃα〕２０Ｄ
＝−８，６１（ｎｅａｔ）、７８％ｅ、 ｅ、 ）、ラ
ネーニッケル１００ｍ１、シクロヘキサン１０ｍ１を仕
込み、水素圧７．０気圧、温度１２５℃その他は実施例
１と同様に反応、後処理を行った。蒸留後１−メチル−
３−フェニルプロピルアミン８８０ｍｇ（〔α：）
＝−０，５９（ｎｅａｔ）、５．５％ｅ、ｅ、） ヲ得
り
た。収率８８％、ラセミ化率９３％。Example 2 A 50 mJ glass autoclave was charged with (1-methyl-3-phenylpropylamine (Cα) 20D = -8,61 (neat), 78% e, e, ), 100 ml of Raney nickel, and 10 ml of cyclohexane. The reaction and post-treatment were carried out in the same manner as in Example 1 except for the hydrogen pressure of 7.0 atm and the temperature of 125°C.After distillation, 1-methyl-
3-phenylpropylamine 880mg ([α:)
= -0,59 (neat), 5.5% e, e,) was obtained. Yield 88%, racemization rate 93%.
実施例３
５０ｍ１！のガラス製オートクレーブに（８）−１−メ
チル−３−フェニルプロピルアミン１５！（Ｃα〕；０
＝ ＋ ５．０４ （ｎｅａｔ）、４７％ｅ、ｅ、）、
ラネーコバルトｔｏｏｍ、ｐ、＋−ルエン１０１／を
仕込み、水素圧８．５気圧、温度１８０℃その他は実施
例１と同様に反応、後処理を行った。蒸留後、１−メチ
ル−３−フェニルプロピルアミン６３０ｍ、９（〔α〕
＝±０．００ （ｎｅａｔ）、０．２％ｅ、ｅ、）を
得り
た。収率６３％、ラセミ化率１００％。Example 3 50m1! (8)-1-Methyl-3-phenylpropylamine 15! (Cα];0
= + 5.04 (neat), 47%e, e,),
Raney cobalt toom,p,+-toluene (101/) was charged, and the reaction and post-treatment were carried out in the same manner as in Example 1 except for the hydrogen pressure of 8.5 atm and the temperature of 180°C. After distillation, 1-methyl-3-phenylpropylamine 630m, 9([α]
= ±0.00 (neat), 0.2% e, e, ) was obtained. Yield 63%, racemization rate 100%.
実施例４
５０ｍＪのガラス製オートクレーブにＲ−にメチル−３
−フェニルプロピルアミン５００ ｍｌ！；！（〔α〕
ゎ＝−１９，０°（Ｃ＝５．シクロヘキサン）、９８％
ｅ、 ｅ、 ）、ラネーコバルト２５０ｍ、９，１−ル
エン１０ｍＪを仕込み、水素圧７．０気圧、温度１２５
℃その他は実施例１と同様に反応を行なった。得られた
オイル４７０ｍ、９を酢エチ９ｍｌに溶解し、４．３Ｎ
ＨＣＩのＴＩ（Ｆ溶液１．５ ｍＪを（ｃ＝１．エ
タノール）、２７％ｅ、ｅ、） ｆ得た。Example 4 Methyl-3 to R- in a 50 mJ glass autoclave
-Phenylpropylamine 500 ml! ;! ([α]
ゎ = -19,0° (C = 5. cyclohexane), 98%
e, e, ), 250 m of Raney cobalt, 10 mJ of 9,1-luene, hydrogen pressure 7.0 atm, temperature 125
C. The reaction was carried out in the same manner as in Example 1 except for the temperature. Dissolve 470ml of the obtained oil in 9ml of acetic acid and add 4.3N
TI of HCI (1.5 mJ of F solution (c=1.ethanol), 27% e, e,) f was obtained.
収率７０％、ラセミ化率７３％。Yield 70%, racemization rate 73%.
実施例５
実施例１のラネーニッケルのかわりに還元ニラ１フル（
１２２ＡＲ８，８揮化学製）５０ｍ、９を用いて同様に
反応、後処理を行なった。蒸留後１−メチル−３−フェ
ニルプロピルアミン２６５ｍｇ（〔α：ｌ＝＋２．５１
°、２３％ｅ、 ｅ、 ）を得た。Example 5 In place of the Raney nickel in Example 1, one full reduced chive (
The reaction and post-treatment were carried out in the same manner using 122AR8,8 (Kokugaku Kagaku) 50m,9. After distillation, 265 mg of 1-methyl-3-phenylpropylamine ([α:l=+2.51
°, 23% e, e, ) was obtained.
収率５３％、ラセミ化率６６％。Yield 53%, racemization rate 66%.
特許出願人 鐘淵化学工業株式会社
代理人 弁理士 浅 野 真 −
手続補正書
昭和６２年１２月ｌ？日
１、事件の表示
昭和６２５１′ 特許 願第０１６８４２号２、発明の
名称
光学活性アミンのラセミ化法
３、補正する者
事件との関係 特許出願人
氏 名（名称）代表者 新 納 眞 人４、代理人
５、補正命令の日付 自発
６、補正により増加する発明の数
７、補正の対象
ｔｌ） 発明の詳細な説明の欄の補正明細書第８頁下
から３行目
「収率５３％、ラセミ化率６６％。」の下に、次の実施
例６および７の記載を加入します。Patent applicant Kanekabuchi Chemical Co., Ltd. agent Patent attorney Makoto Asano - Procedural amendment December 1988 l? Day 1, Indication of the case Showa 6251' Patent Application No. 016842 2, Name of the invention Process for racemization of optically active amines 3, Relationship with the case by the person making the amendment Patent applicant name (name) Representative Makoto Shinno 4 , Agent 5, Date of amendment order Voluntary 6, Number of inventions increased by amendment 7, Subject of amendment tl) 3rd line from the bottom of page 8 of the amended specification in the column of detailed explanation of the invention "Yield 53% , racemization rate 66%.'' The following descriptions of Examples 6 and 7 are added.
実施例６
５００ｍ／容ステンレス製オートクレーブに、（Ｓ）−
１−メチル−３−フェニルプロピルアミンｉｏ、ｏ、ｙ
（光学純度 ５１．０％ｅ、 ｅ、 ）、ラネーコバル
ト０．５，９．トルエン１００ｍＪを仕込み、減圧脱気
後、水素圧２．５気圧、温度１２０℃で１６時間反応し
た。反応終了後、冷却、開封し、反応液を濾過して触媒
を除き、Ｆ液を＠縮し、淡黄色オイル９．９ ｊｉを得
た。これを蒸留し、１−メチル−３−フェニルプロピル
アミン９．５ｙを得た。Example 6 In a 500 m/capacity stainless steel autoclave, (S)-
1-Methyl-3-phenylpropylamine io, o, y
(optical purity 51.0% e, e, ), Raney cobalt 0.5,9. 100 mJ of toluene was charged, and after degassing under reduced pressure, the reaction was carried out at a hydrogen pressure of 2.5 atm and a temperature of 120° C. for 16 hours. After the reaction was completed, the container was cooled and opened, the reaction solution was filtered to remove the catalyst, and the F solution was condensed to obtain a pale yellow oil (9.9 ji). This was distilled to obtain 9.5y of 1-methyl-3-phenylpropylamine.
に、ラセミ化率ｉｏｏに。and the racemization rate ioo.
実施例７
５ＵＯｍ／容ステンレス製オートクレーブに、（Ｓ）−
１−メチル−３−フェニルプロピルアミン１２０！９（
光学純度 ５５．０％ｅ、ｅ、）、ラネーコバルト１０
．０．９を仕込み、減圧脱気後、水素圧２，５気圧、温
度１２０℃で５時間反応した。反応終了後、濾過により
触媒を除去し、淡黄色オイル１１９．５．！７を得た。Example 7 In a 5UOm/capacity stainless steel autoclave, (S)-
1-Methyl-3-phenylpropylamine 120!9 (
Optical purity 55.0% e, e,), Raney cobalt 10
．． After degassing under reduced pressure, the reaction mixture was reacted for 5 hours at a hydrogen pressure of 2.5 atm and a temperature of 120°C. After the reaction was completed, the catalyst was removed by filtration, leaving a pale yellow oil 119.5. ! I got a 7.
このものを蒸留し、１−メチル−３−フェニル（ｎｅａ
ｔ）、０％ｅ、 ｅ、、収率９６％、ラセミ化率１００
％。This product was distilled and 1-methyl-3-phenyl (nea
t), 0% e, e,, yield 96%, racemization rate 100
%.
Claims (1)
ン及びその酸付加塩を水素圧１０気圧より低圧下で接触
還元触媒と共に加熱反応させることを特徴とする光学活
性１−メチル−３−フェニルプロピルアミンのラセミ化
方法。(1) Optically active 1-methyl-3-phenylpropylamine is produced by heating and reacting optically active 1-methyl-3-phenylpropylamine and its acid addition salt with a catalytic reduction catalyst under a hydrogen pressure lower than 10 atmospheres. Racemization method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62016842A JPS63185943A (en) | 1987-01-27 | 1987-01-27 | Racemization of optically active amine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62016842A JPS63185943A (en) | 1987-01-27 | 1987-01-27 | Racemization of optically active amine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63185943A true JPS63185943A (en) | 1988-08-01 |
Family
ID=11927462
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62016842A Pending JPS63185943A (en) | 1987-01-27 | 1987-01-27 | Racemization of optically active amine |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63185943A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5969186A (en) * | 1996-03-28 | 1999-10-19 | Nagase & Company, Ltd. | Process for racemizing of optically active amines |
| WO2000047546A1 (en) * | 1999-02-12 | 2000-08-17 | Basf Aktiengesellschaft | Method for the racemization of optically active amines |
| WO2001096301A1 (en) * | 2000-06-14 | 2001-12-20 | Toray Industries, Inc. | Processes for producing racemic piperidine derivative and for producing optically active piperidine derivative |
| FR2875498A1 (en) * | 2004-09-22 | 2006-03-24 | Centre Nat Rech Scient | PROCESS FOR THE PARTIAL OR TOTAL INVERSION OF AMINE CONFIGURATION |
| CN114057640A (en) * | 2020-08-05 | 2022-02-18 | 凯特立斯（深圳）科技有限公司 | Asymmetric synthesis method of optically pure (R)/(S) -hydroxychloroquine side chain |
-
1987
- 1987-01-27 JP JP62016842A patent/JPS63185943A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5969186A (en) * | 1996-03-28 | 1999-10-19 | Nagase & Company, Ltd. | Process for racemizing of optically active amines |
| WO2000047546A1 (en) * | 1999-02-12 | 2000-08-17 | Basf Aktiengesellschaft | Method for the racemization of optically active amines |
| WO2001096301A1 (en) * | 2000-06-14 | 2001-12-20 | Toray Industries, Inc. | Processes for producing racemic piperidine derivative and for producing optically active piperidine derivative |
| US6962998B2 (en) | 2000-06-14 | 2005-11-08 | Toray Industries, Inc. | Processes for producing racemic piperidine derivative and for producing optically active piperidine derivative |
| FR2875498A1 (en) * | 2004-09-22 | 2006-03-24 | Centre Nat Rech Scient | PROCESS FOR THE PARTIAL OR TOTAL INVERSION OF AMINE CONFIGURATION |
| WO2006032776A1 (en) * | 2004-09-22 | 2006-03-30 | Centre National De La Recherche Scientifique | Method for partial or total inversion of an amine configuration |
| CN114057640A (en) * | 2020-08-05 | 2022-02-18 | 凯特立斯（深圳）科技有限公司 | Asymmetric synthesis method of optically pure (R)/(S) -hydroxychloroquine side chain |
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