JPH07138210A - Production of aminopropane derivative - Google Patents
Production of aminopropane derivativeInfo
- Publication number
- JPH07138210A JPH07138210A JP5314454A JP31445493A JPH07138210A JP H07138210 A JPH07138210 A JP H07138210A JP 5314454 A JP5314454 A JP 5314454A JP 31445493 A JP31445493 A JP 31445493A JP H07138210 A JPH07138210 A JP H07138210A
- Authority
- JP
- Japan
- Prior art keywords
- dimethylphenoxy
- aminopropane
- propanone
- present
- water
- 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
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 13
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 title 1
- VLPIATFUUWWMKC-UHFFFAOYSA-N mexiletine Chemical compound CC(N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-UHFFFAOYSA-N 0.000 claims abstract description 11
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910000564 Raney nickel Inorganic materials 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 10
- XDJULAUHYAJQBU-UHFFFAOYSA-N 1-(2,6-dimethylphenoxy)propan-2-one Chemical compound CC(=O)COC1=C(C)C=CC=C1C XDJULAUHYAJQBU-UHFFFAOYSA-N 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 4
- 239000012046 mixed solvent Substances 0.000 claims abstract description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 16
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 abstract description 10
- 239000002994 raw material Substances 0.000 abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 150000001875 compounds Chemical class 0.000 description 8
- -1 conventionally Chemical compound 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000013076 target substance Substances 0.000 description 3
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- DPLCQNGJZJXXPM-UHFFFAOYSA-N 1-(3,5-dimethylphenoxy)propan-2-amine Chemical compound CC(N)COC1=CC(C)=CC(C)=C1 DPLCQNGJZJXXPM-UHFFFAOYSA-N 0.000 description 1
- FOTWPARMSCBQBA-UHFFFAOYSA-N 1-(3,5-dimethylphenoxy)propan-2-one Chemical compound CC(=O)COC1=CC(C)=CC(C)=C1 FOTWPARMSCBQBA-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960004592 isopropanol Drugs 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- NFEIBWMZVIVJLQ-UHFFFAOYSA-N mexiletine hydrochloride Chemical compound [Cl-].CC([NH3+])COC1=C(C)C=CC=C1C NFEIBWMZVIVJLQ-UHFFFAOYSA-N 0.000 description 1
- 229960001070 mexiletine hydrochloride Drugs 0.000 description 1
- 150000002923 oximes Chemical group 0.000 description 1
- ISYORFGKSZLPNW-UHFFFAOYSA-N propan-2-ylazanium;chloride Chemical compound [Cl-].CC(C)[NH3+] ISYORFGKSZLPNW-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 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
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医薬品、例えば塩酸メ
キシレチンの中間体として有用な１−（２，６−ジメチ
ルフェノキシ）−２−アミノプロパンの製造方法に関す
る。FIELD OF THE INVENTION The present invention relates to a method for producing 1- (2,6-dimethylphenoxy) -2-aminopropane which is useful as an intermediate for pharmaceuticals such as mexiletine hydrochloride.
【０００２】[0002]
【従来の技術・発明が解決しようとする課題】１−
（２，６−ジメチルフェノキシ）−２−アミノプロパン
の製造方法としては、従来、１−（２，６−ジメチル
フェノキシ）−２−プロパノンから、一旦オキシム体と
し、次いで、メタノール溶媒中ラニーニッケルを触媒と
し、６０℃、６気圧の下で水素添加により還元する方法
（特公昭４５−３１９３０号公報）、１−メチル−２
−（２，６−ジメチルフェノキシ）エチル−メタンスル
ホン酸エステルにアンモニアをメタノール中で反応させ
る方法（フィンランド公開第５４２９２号公報）等が開
示されている。また、目的化合物は異なるが、１−
（３，５−ジメチルフェノキシ）−２−プロパノンを、
含水アルコール中、アンモニアおよびラニーニッケル触
媒の存在下、高圧の水素圧（例えば１８〜４０気圧）の
下で還元的にアミノ化することにより１−（３，５−ジ
メチルフェノキシ）−２−アミノプロパンを製造する方
法等が開示されている（特開平５−３９２４９号公
報）。[Problems to be Solved by Conventional Techniques and Inventions] 1-
As a method for producing (2,6-dimethylphenoxy) -2-aminopropane, conventionally, 1- (2,6-dimethylphenoxy) -2-propanone was once converted into an oxime form, and then Raney nickel in a methanol solvent was used. Method of reducing by hydrogenation at 60 ° C. and 6 atm as a catalyst (JP-B-45-31930), 1-methyl-2
A method of reacting-(2,6-dimethylphenoxy) ethyl-methanesulfonic acid ester with ammonia in methanol (Finnish Publication No. 54292) is disclosed. Although the target compound is different,
(3,5-dimethylphenoxy) -2-propanone,
1- (3,5-dimethylphenoxy) -2-aminopropane by reductive amination in a hydrous alcohol in the presence of ammonia and a Raney nickel catalyst under a high hydrogen pressure (eg 18 to 40 atm). Japanese Patent Laid-Open No. 5-39249 has been disclosed.
【０００３】しかしながら、方法では、カルボニル基
からアミノ基へ変換するのに２工程を要し、またメタノ
ールを溶媒とするためラニーニッケル触媒の取扱いに注
意を必要とする。方法では、原料エステルに対し約３
８倍モルものアンモニアを用いるにもかかわらず収率が
十分でない。従って、これらの方法では１−（２，６−
ジメチルフェノキシ）−２−アミノプロパンの製造方法
としては工業的に有利であるとはいえない。一方、の
方法では、目的の化合物が異なり、本発明が課題として
いる１−（２，６−ジメチルフェノキシ）−２−アミノ
プロパンについては全く開示されていない。さらに、高
圧の水素圧下で行う方法であるため、本発明における目
的化合物の製造に応用するとしても工業的に安全かつ有
利な方法とは言えない。従って、さらに工業的に有利な
１−（２，６−ジメチルフェノキシ）−２−アミノプロ
パンの製造方法の開発が要望されているのが現状であ
る。However, the method requires two steps for converting a carbonyl group to an amino group and requires careful handling of the Raney nickel catalyst because methanol is used as a solvent. In the method, about 3 to the raw material ester
Despite the use of 8 times as much ammonia, the yield is not sufficient. Therefore, in these methods, 1- (2,6-
It cannot be said that it is industrially advantageous as a method for producing dimethylphenoxy) -2-aminopropane. On the other hand, in the method 1, the target compound is different, and 1- (2,6-dimethylphenoxy) -2-aminopropane, which is the subject of the present invention, is not disclosed at all. Further, since the method is carried out under a high pressure of hydrogen, it cannot be said to be industrially safe and advantageous even when applied to the production of the target compound in the present invention. Therefore, at present, there is a demand for the development of a more industrially advantageous method for producing 1- (2,6-dimethylphenoxy) -2-aminopropane.
【０００４】本発明の目的は、高純度の１−（２，６−
ジメチルフェノキシ）−２−アミノプロパンを安価な原
料から１工程で簡易かつ高収率に工業的に有利に製造す
ることができる新規な方法を提供することにある。The object of the present invention is to obtain highly pure 1- (2,6-
It is an object of the present invention to provide a novel method capable of industrially advantageously producing dimethylphenoxy) -2-aminopropane from an inexpensive raw material in a single step in a simple and high yield.
【０００５】[0005]
【課題を解決するための手段】本発明者らは、上記の目
的を達成するため、１−（２，６−ジメチルフェノキ
シ）−２−アミノプロパンの製造方法を種々検討したと
ころ、１−（２，６−ジメチルフェノキシ）−２−プロ
パノンからアンモニアを含む含水アルコール中におい
て、ラニーニッケル触媒の存在下に約１気圧の水素ガス
を用いて３０〜５５℃で接触還元することにより、安価
な原料から１工程で、簡易かつ安全に高収率で目的の１
−（２，６−ジメチルフェノキシ）−２−アミノプロパ
ンを製造し得ることを見出した。本発明は、これらの知
見に基づきさらに研究を進めた結果完成するに至ったも
のである。Means for Solving the Problems In order to achieve the above object, the present inventors have studied various methods for producing 1- (2,6-dimethylphenoxy) -2-aminopropane. An inexpensive raw material obtained by catalytic reduction of 2,6-dimethylphenoxy) -2-propanone in a hydrous alcohol containing ammonia in the presence of a Raney nickel catalyst using hydrogen gas at about 1 atm at 30 to 55 ° C. 1 step from 1 to 1 easily and safely with high yield
It was found that-(2,6-dimethylphenoxy) -2-aminopropane can be produced. The present invention has been completed as a result of further research based on these findings.
【０００６】即ち、本発明の要旨は、１−（２，６−ジ
メチルフェノキシ）−２−プロパノンを、ラニーニッケ
ル触媒の存在下、アンモニアを含む炭素原子数１〜５の
脂肪族アルコールと水の混合溶媒中で、３０〜５５℃に
おいて１〜１．２気圧の水素ガスにより、還元的にアミ
ノ化することを特徴とする１−（２，６−ジメチルフェ
ノキシ）−２−アミノプロパンの製造方法に関する。That is, the gist of the present invention is to convert 1- (2,6-dimethylphenoxy) -2-propanone into an aliphatic alcohol having 1 to 5 carbon atoms containing ammonia and water in the presence of a Raney nickel catalyst. A method for producing 1- (2,6-dimethylphenoxy) -2-aminopropane, which comprises reductively aminating with hydrogen gas at 1 to 1.2 atm at 30 to 55 ° C. in a mixed solvent. Regarding
【０００７】以下に、本発明について詳細に説明する。
本反応のスキームは、次の通りである。The present invention will be described in detail below.
The scheme of this reaction is as follows.
【０００８】[0008]
【化１】 [Chemical 1]
【０００９】本発明の製造方法に使用される１−（２，
６−ジメチルフェノキシ）−２−プロパノン（式（Ｉ）
の化合物）は、２，６−ジメチルフェノールにモノクロ
ロアセトンを反応させることにより製造することができ
る。1- (2 used in the production method of the present invention
6-dimethylphenoxy) -2-propanone (formula (I)
Can be produced by reacting 2,6-dimethylphenol with monochloroacetone.
【００１０】ラニーニッケル触媒は市販のものを使用す
ることができる。その使用量は、原料化合物である式
（Ｉ）の化合物に対して通常５〜５０重量％であり、好
ましくは、１０〜３０重量％である。水素圧は、常圧付
近で行われ、好ましくは１〜１．２気圧である。また、
反応温度は１０〜１００℃であるが、特に反応収率の点
から３０〜５５℃が好ましい。A commercially available Raney nickel catalyst can be used. The amount used is usually 5 to 50% by weight, preferably 10 to 30% by weight, based on the compound of the formula (I) as the starting compound. The hydrogen pressure is set to near normal pressure, preferably 1 to 1.2 atm. Also,
The reaction temperature is 10 to 100 ° C., but 30 to 55 ° C. is particularly preferable from the viewpoint of reaction yield.
【００１１】本発明の製造方法に使用される含水アルコ
ール中のアルコールと水の容積比は、通常７０：３０〜
３０：７０、好ましくは、５５：４５〜４５：５５であ
る。使用される炭素原子数１〜５の脂肪族アルコールと
しては、メタノール、エタノール、ｎ−プロパノール、
ｉｓｏ−プロパノール、ｎ−ブタノール、ｔ−ブタノー
ル、ペンタノール等が挙げられる。The volume ratio of alcohol to water in the hydrous alcohol used in the production method of the present invention is usually 70:30 to.
30:70, preferably 55:45 to 45:55. As the aliphatic alcohol having 1 to 5 carbon atoms to be used, methanol, ethanol, n-propanol,
Examples include iso-propanol, n-butanol, t-butanol, pentanol and the like.
【００１２】本発明の製造方法に使用されるアンモニア
は、アンモニアガスとして含水アルコール中に溶解せし
めてもよいが、アンモニア水を含水アルコールに添加す
ることが好ましい。アンモニア水の使用量は、原料化合
物である式（Ｉ）の化合物に対してＮＨ3 として２〜５
倍モルである。The ammonia used in the production method of the present invention may be dissolved in the hydrous alcohol as ammonia gas, but it is preferable to add the ammonia water to the hydrous alcohol. The amount of ammonia water used is 2 to 5 as NH 3 with respect to the compound of the formula (I) which is a raw material compound.
It is twice the mole.
【００１３】本発明の反応における反応時間は、反応温
度にもよるが、通常１〜１０時間であり、薄層クロマト
グラフィーにより原料である１−（２，６−ジメチルフ
ェノキシ）−２−プロパノン（式（Ｉ）の化合物）が消
失した時点で終了させる。Although the reaction time in the reaction of the present invention depends on the reaction temperature, it is usually 1 to 10 hours, and 1- (2,6-dimethylphenoxy) -2-propanone (which is a starting material by thin layer chromatography is used. It is terminated when the compound of formula (I) disappears.
【００１４】反応終了後、目的の１−（２，６−ジメチ
ルフェノキシ）−２−アミノプロパン（式（II）の化合
物）を反応液から単離するには、通常の方法による。例
えば、反応液から触媒を分離除去し、ついで塩化メチレ
ンで２回抽出し、抽出液を減圧下に濃縮し、残留物を酢
酸エチルに溶解した後、酢酸エチル−塩酸混液を加えて
酸性とし、析出する結晶を濾過乾燥し、目的物を塩酸塩
として得ることができる。After completion of the reaction, the desired 1- (2,6-dimethylphenoxy) -2-aminopropane (compound of formula (II)) is isolated from the reaction solution by a conventional method. For example, the catalyst is separated and removed from the reaction solution, then extracted twice with methylene chloride, the extract solution is concentrated under reduced pressure, the residue is dissolved in ethyl acetate, and then an ethyl acetate-hydrochloric acid mixture solution is added to acidify it. The precipitated crystals can be filtered and dried to obtain the desired product as a hydrochloride.
【００１５】[0015]
【実施例】以下、実施例および比較例により本発明をさ
らに詳しく説明するが、本発明はこれらの実施例等によ
りなんら限定されるものではない。EXAMPLES The present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.
【００１６】実施例１ ５００ｍｌのコルベンに、１−（２，６−ジメチルフェ
ノキシ）−２−プロパノンの３５．６ｇ（０．２モ
ル）、ラニーニッケル触媒５．４ｇ、溶媒として水５０
ｍｌ、メタノール８０ｍｌを加え、ついで２９％アンモ
ニア水４１．０ｇ（０．７モル）を加えた。このときの
水とメタノールの容積比は約１：１であった。この溶液
を水素１気圧の条件下で、７時間、３５℃において接触
還元した。反応終了後、触媒を分離し反応液に塩化メチ
レン３６ｍｌを加えて抽出し、さらに塩化メチレン１２
ｍｌで再度抽出した後、抽出液を合わせ、減圧下に濃縮
した。得られた残留物を酢酸エチルで溶解した後、酢酸
エチル−塩酸混液で酸性とし、析出した結晶を濾過乾燥
して目的物質の１−（２，６−ジメチルフェノキシ）−
２−アミノプロパンの塩酸塩３２．３ｇ（０．１５モ
ル）を得た。収率は７５％、融点は２００〜２０３℃で
あった。Example 1 In 500 ml of Kolben, 35.6 g (0.2 mol) of 1- (2,6-dimethylphenoxy) -2-propanone, 5.4 g of Raney nickel catalyst, and 50 as water as a solvent.
ml and 80 ml of methanol were added, and then 41.0 g (0.7 mol) of 29% aqueous ammonia was added. The volume ratio of water to methanol at this time was about 1: 1. This solution was catalytically reduced under the condition of 1 atm of hydrogen for 7 hours at 35 ° C. After the reaction was completed, the catalyst was separated, and 36 ml of methylene chloride was added to the reaction solution for extraction.
After extracting again with ml, the extracts were combined and concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate, acidified with a mixed solution of ethyl acetate-hydrochloric acid, and the precipitated crystals were filtered and dried to give 1- (2,6-dimethylphenoxy) -of the target substance.
32.3 g (0.15 mol) of the hydrochloride of 2-aminopropane was obtained. The yield was 75% and the melting point was 200 to 203 ° C.
【００１７】実施例２ メタノール８０ｍｌの代わりにメタノール４０ｍｌを使
用して水とメタノールの容積比を約２：１にすること以
外は、実施例１と同様の条件を用いて、１−（２，６−
ジメチルフェノキシ）−２−プロパノンの３５．６ｇ
（０．２モル）を接触還元して目的物質の１−（２，６
−ジメチルフェノキシ）−２−アミノプロパンの塩酸塩
２８．５ｇ（０．１３２モル）を得た。収率は６６％、
融点は２００〜２０３℃であった。Example 2 Using the same conditions as in Example 1 except that 40 ml of methanol was used instead of 80 ml of methanol and the volume ratio of water to methanol was about 2: 1, 1- (2, 6-
35.6 g of dimethylphenoxy) -2-propanone
(0.2 mol) is catalytically reduced to give 1- (2,6) of the target substance.
28.5 g (0.132 mol) of the hydrochloride salt of -dimethylphenoxy) -2-aminopropane was obtained. 66% yield,
The melting point was 200 to 203 ° C.
【００１８】実施例３ 水５０ｍｌの代わりに水９０ｍｌを使用して水とメタノ
ールの容積比を約３：２にする以外は、実施例１と同様
の条件を用いて、１−（２，６−ジメチルフェノキシ）
−２−プロパノンの３５．６ｇ（０．２モル）を接触還
元して目的物質の１−（２，６−ジメチルフェノキシ）
−２−アミノプロパンの塩酸塩２８．０ｇ（０．１３０
モル）を得た。収率は６５％、融点は２００〜２０３℃
であった。Example 3 1- (2,6) was used under the same conditions as in Example 1 except that 90 ml of water was used instead of 50 ml of water and the volume ratio of water to methanol was set to about 3: 2. -Dimethylphenoxy)
-2-propanone (35.6 g, 0.2 mol) was catalytically reduced to give 1- (2,6-dimethylphenoxy) as a target substance.
28.0 g of 2-aminopropane hydrochloride (0.130
Mol) was obtained. Yield 65%, melting point 200-203 ℃
Met.
【００１９】比較例 １−（２，６−ジメチルフェノキシ）−２−プロパノン
の１０ｇ（０．０５６モル）をメタノール５０ｍｌに溶
解し、塩酸ヒドロキシルアミンの７．８ｇ（０．１１２
モル）を加え、５０％水酸化ナトリウムでｐＨを７と
し、５０〜６０℃て約２時間反応した後、ラニーニッケ
ル触媒を加え、６０℃にて６気圧の水素加圧下に接触還
元した。反応終了後、触媒を分離し、メタノールを留去
して得られた残留物をエタノールに溶かし、エーテル−
塩酸混液を添加して析出した結晶を濾過・乾燥し、１−
（２，６−ジメチルフェノキシ）−２−アミノプロパン
の塩酸塩６．３ｇ（０．００２９モル）を得た。収率は
５２％、融点は２０１〜２０３℃であった。Comparative Example 10 g (0.056 mol) of 1- (2,6-dimethylphenoxy) -2-propanone was dissolved in 50 ml of methanol, and 7.8 g (0.112) of hydroxylamine hydrochloride was added.
Mol) was added, the pH was adjusted to 7 with 50% sodium hydroxide, and the mixture was reacted at 50 to 60 ° C. for about 2 hours. Then, a Raney nickel catalyst was added, and catalytic reduction was performed at 60 ° C. under hydrogen pressure of 6 atm. After completion of the reaction, the catalyst was separated, methanol was distilled off, and the resulting residue was dissolved in ethanol, and then ether-
A mixed solution of hydrochloric acid was added, and the precipitated crystals were filtered and dried.
6.3 g (0.0029 mol) of (2,6-dimethylphenoxy) -2-aminopropane hydrochloride was obtained. The yield was 52% and the melting point was 201 to 203 ° C.
【００２０】[0020]
【発明の効果】本発明の製造方法によれば、安価な原料
である１−（２，６−ジメチルフェノキシ）−２−プロ
パノンから１工程で簡易かつ安全に高収率に１−（２，
６−ジメチルフェノキシ）−２−アミノプロパンを製造
することができる。EFFECTS OF THE INVENTION According to the production method of the present invention, 1- (2,6-dimethylphenoxy) -2-propanone, which is an inexpensive raw material, can be produced simply and safely in a high yield in a single step in 1- (2,2
6-Dimethylphenoxy) -2-aminopropane can be produced.
Claims (1)
２−プロパノンを、ラニーニッケル触媒の存在下、アン
モニアを含む炭素原子数１〜５の脂肪族アルコールと水
の混合溶媒中で、３０〜５５℃において、１〜１．２気
圧の水素ガスにより、還元的にアミノ化することを特徴
とする１−（２，６−ジメチルフェノキシ）−２−アミ
ノプロパンの製造方法。1. 1- (2,6-dimethylphenoxy)-
2-propanone was treated with hydrogen gas at 1 to 1.2 atm at 30 to 55 ° C in a mixed solvent of an aliphatic alcohol having 1 to 5 carbon atoms containing ammonia and water in the presence of a Raney nickel catalyst. A method for producing 1- (2,6-dimethylphenoxy) -2-aminopropane, which comprises reductive amination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5314454A JPH07138210A (en) | 1993-11-19 | 1993-11-19 | Production of aminopropane derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5314454A JPH07138210A (en) | 1993-11-19 | 1993-11-19 | Production of aminopropane derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07138210A true JPH07138210A (en) | 1995-05-30 |
Family
ID=18053549
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5314454A Pending JPH07138210A (en) | 1993-11-19 | 1993-11-19 | Production of aminopropane derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07138210A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001288150A (en) * | 2000-04-03 | 2001-10-16 | Idemitsu Kosan Co Ltd | Method for producing phenoxyalkylamine salt |
| CN105017033A (en) * | 2015-06-10 | 2015-11-04 | 山西云鹏制药有限公司 | Process for producing mexiletine hydrochloride |
| CN107641074A (en) * | 2017-09-19 | 2018-01-30 | 常州亚邦制药有限公司 | The production method of mexiletine hydrochloride |
| CN109384681A (en) * | 2017-08-11 | 2019-02-26 | 南京理工大学 | A kind of method of synthetic hydrochloric acid mexiletine |
-
1993
- 1993-11-19 JP JP5314454A patent/JPH07138210A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001288150A (en) * | 2000-04-03 | 2001-10-16 | Idemitsu Kosan Co Ltd | Method for producing phenoxyalkylamine salt |
| CN105017033A (en) * | 2015-06-10 | 2015-11-04 | 山西云鹏制药有限公司 | Process for producing mexiletine hydrochloride |
| CN109384681A (en) * | 2017-08-11 | 2019-02-26 | 南京理工大学 | A kind of method of synthetic hydrochloric acid mexiletine |
| CN109384681B (en) * | 2017-08-11 | 2021-11-09 | 南京理工大学 | Method for synthesizing mexiletine hydrochloride |
| CN107641074A (en) * | 2017-09-19 | 2018-01-30 | 常州亚邦制药有限公司 | The production method of mexiletine hydrochloride |
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