JPH0466558A - Production of 2-aminoindane - Google Patents
Production of 2-aminoindaneInfo
- Publication number
- JPH0466558A JPH0466558A JP2172235A JP17223590A JPH0466558A JP H0466558 A JPH0466558 A JP H0466558A JP 2172235 A JP2172235 A JP 2172235A JP 17223590 A JP17223590 A JP 17223590A JP H0466558 A JPH0466558 A JP H0466558A
- Authority
- JP
- Japan
- Prior art keywords
- aminoindan
- formula
- compound
- indanone oxime
- nickel
- 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
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 title claims description 31
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims abstract description 33
- UJLFLOAXKVGYIA-UHFFFAOYSA-N indan-2-one oxime Chemical compound C1=CC=C2CC(=NO)CC2=C1 UJLFLOAXKVGYIA-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 239000002798 polar solvent Substances 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 2
- 239000003054 catalyst Substances 0.000 abstract description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 13
- 229910052759 nickel Inorganic materials 0.000 abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 abstract description 6
- 239000005909 Kieselgur Substances 0.000 abstract description 5
- 239000006227 byproduct Substances 0.000 abstract description 5
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 abstract description 5
- 239000000292 calcium oxide Substances 0.000 abstract description 5
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 239000000377 silicon dioxide Substances 0.000 abstract description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 3
- 206010020772 Hypertension Diseases 0.000 abstract description 2
- 206010003119 arrhythmia Diseases 0.000 abstract description 2
- 230000006793 arrhythmia Effects 0.000 abstract description 2
- 208000019622 heart disease Diseases 0.000 abstract description 2
- 239000000395 magnesium oxide Substances 0.000 abstract description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 abstract description 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 21
- 238000000034 method Methods 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 6
- 238000000926 separation method Methods 0.000 description 5
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 4
- XEHNLVMHWYPNEQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-amine;hydron;chloride Chemical group Cl.C1=CC=C2CC(N)CC2=C1 XEHNLVMHWYPNEQ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000004157 Nitrosyl chloride Substances 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 2
- 235000019392 nitrosyl chloride Nutrition 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WMRAEEYGNITLSE-UHFFFAOYSA-N 1-chloro-2-nitroso-2,3-dihydro-1h-indene Chemical compound C1=CC=C2C(Cl)C(N=O)CC2=C1 WMRAEEYGNITLSE-UHFFFAOYSA-N 0.000 description 1
- XJEVHMGJSYVQBQ-UHFFFAOYSA-N 2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2C(N)CCC2=C1 XJEVHMGJSYVQBQ-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 239000003426 co-catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000002469 indenes Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- -1 methanol and ethanol Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 231100000004 severe toxicity Toxicity 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- SFKTYEXKZXBQRQ-UHFFFAOYSA-J thorium(4+);tetrahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[Th+4] SFKTYEXKZXBQRQ-UHFFFAOYSA-J 0.000 description 1
- 238000005292 vacuum distillation 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
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は薬理学上、と（に不整脈症などの各種心臓病・
高血圧症および喘息などの予防・治療剤の原料として有
用な、２−アミノインダンの製造方法に関する。[Detailed Description of the Invention] <Industrial Field of Application> The present invention is useful for pharmacological purposes, including various heart diseases such as arrhythmia,
The present invention relates to a method for producing 2-aminoindan, which is useful as a raw material for preventive and therapeutic agents for hypertension, asthma, and the like.
〈従来の技術〉
２−アミノインダンの誘導体は一般にすぐれた生理活性
作用を示し、各種医薬に利用されるという例が多数報告
されている（たとえば、特公昭５４−６５５ １号、特
公昭６２−１２２１４号、特公昭６２−１２８００号、
Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈ
ｅｍｉｓｔｒｙ， Ｖｏｌ．９。<Prior Art> Derivatives of 2-aminoindan generally exhibit excellent physiological activity, and there have been many reports of their use in various medicines (for example, Japanese Patent Publication No. 655-1 of 1983, Japanese Patent Publication No. 62-1983). No. 12214, Special Publication No. 62-12800,
The Journal of Organic Ch.
emistry, Vol. 9.
Ｐ． ３８０−３９１， （１９４４）など）。 これ
らの報告によれば、当該化合物を成分とした医薬は効能
が高いわりに従来品と比べて副作用が少ないという特徴
を持っている。 一方、その構造の核となる２−アミノ
インダンの製造方法も種々検討されているが、現在工業
的に有効な方法は見出されていない。P. 380-391, (1944), etc.). According to these reports, medicines containing such compounds are highly effective and have fewer side effects than conventional products. On the other hand, although various methods for producing 2-aminoindan, which is the core of its structure, have been studied, no industrially effective method has been found at present.
２−アミノインダンは、インデンの誘導体である２−イ
ンダノンオキシムを還元することにより合成する方法が
従来から一般的に行われている（Ｊｕｓｔｕｓ、 Ａｎ
ｎ、、 Ｖｏｌ、２７５．Ｐ、３５１゜（１８９３））
。 しかしこの方法では同時に第２級アミンであるジイ
ンダニルアミンが副生ずるという問題があった。2-aminoindan has traditionally been synthesized by reducing 2-indanone oxime, which is a derivative of indene (Justus, An.
n,, Vol, 275. P, 351° (1893))
. However, this method also has the problem that diindanylamine, which is a secondary amine, is produced as a by-product.
Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈ
ｅｍｉｓｔｒｙ、 Ｖｏｌ、９゜Ｐ、 ３８０−３９１
． （１９４４）では、ジインダニルアミンの副生を抑
制するために、パラジウムカーボン触媒を用いて塩酸お
よび塩化パラジウムの存在下で２−インダノンオキシム
の還元を行っている。 しかしこの場合の反応生成物は
２−アミノインダンの塩酸塩であることから、さらに水
酸化ナトリウムなどアルカリ類で遊離したのちに溶剤抽
出・濃縮などの操作で２−アミノインダンを分離精製す
る必要がある。 また、この分離工程における収率は６
０％程度と低い。The Journal of Organic Ch.
emistry, Vol, 9゜P, 380-391
．． (1944), 2-indanone oxime is reduced in the presence of hydrochloric acid and palladium chloride using a palladium carbon catalyst in order to suppress the by-product of diindanylamine. However, since the reaction product in this case is 2-aminoindan hydrochloride, it is necessary to further separate and purify 2-aminoindan by operations such as solvent extraction and concentration after liberating it with an alkali such as sodium hydroxide. be. Also, the yield in this separation step is 6
It is low at around 0%.
Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ
Ｃｈｅｍｉｓｔｒｙ、 Ｖｏ１２ｇ、 Ｐ、２７
９７−２８０４．（１９６３）では、ラネーニッケル触
媒を用いて水酸化すトリウムまたはナトリウムメチラー
トなどアルカリの存在下で２−インダノンオキシムの還
元を行うことによりジインダニルアミンの副生を抑制し
ている。 しかし、この場合の反応生成物は多量のア
ルカリを含有しているため、まず濃塩酸をほぼ当量加え
て中和したのち濃縮して、析出した塩を濾過などにより
回収・洗浄し、重質分を除去する。The Journal of Organic
Chemistry, Vo12g, P, 27
97-2804. (1963) suppressed the by-product of diindanylamine by reducing 2-indanone oxime using a Raney nickel catalyst in the presence of an alkali such as thorium hydroxide or sodium methylate. However, since the reaction product in this case contains a large amount of alkali, it is first neutralized by adding approximately an equivalent amount of concentrated hydrochloric acid, then concentrated, and the precipitated salt is collected and washed by filtration, etc., and the heavy remove.
さらに、水酸化ナトリウム水溶液で２−アミノインダン
のみを遊離したのち塩化メチレンなど疎水性の有機溶媒
で抽出して無機塩と分離し、最後に溶媒を留出させると
いう複雑な工程を必要とする。 また、この方法におい
ても収率は６０％程度と低い。Furthermore, it requires a complicated process of liberating only 2-aminoindan with an aqueous sodium hydroxide solution, then extracting it with a hydrophobic organic solvent such as methylene chloride to separate it from inorganic salts, and finally distilling off the solvent. Further, even in this method, the yield is as low as about 60%.
一方、Ａｎｎ、Ｃｈｉｍ、、 Ｖｏｌ、１． Ｎｏ、５
． Ｐ、２６９−２７６（１９７Ｂ）では、２−インダ
ノンオキシムの還元によらずインデンと塩化ニトロシル
から誘導した１−クロロ−２−ニトロソインダンの還元
による合成方法を報告している。 しかし、塩化ニトロ
シルの毒性・腐食性が激しいことや、２アミノインダン
塩酸塩の収率がインデン基準で４５％ときわめて低いな
どの問題があり、有効な方法とは言えない。On the other hand, Ann, Chim, Vol. 1. No, 5
．． P, 269-276 (197B) report a method for the synthesis of 1-chloro-2-nitrosoindane derived from indene and nitrosyl chloride without reduction of 2-indanone oxime. However, there are problems such as the severe toxicity and corrosivity of nitrosyl chloride and the very low yield of 2-aminoindane hydrochloride of 45% based on indene, so it cannot be said to be an effective method.
〈発明が解決しようとする課題〉
上述したように、従来法では２−アミノインダンを合成
または分離する過程で２−アミノインダン塩酸塩を経由
するため、分離操作が複雑となるうえ収率も低かった。<Problems to be solved by the invention> As mentioned above, in the conventional method, 2-aminoindan hydrochloride is passed through in the process of synthesizing or separating 2-aminoindan, which makes the separation operation complicated and has a low yield. Ta.
本発明は、２−アミノインダン塩酸塩を経由することな
く、２−インダノンオキシムの還元および蒸留分離のみ
で２−アミノインダンを製造することにより、従来より
工程を大幅に短縮し、かつ収率を向上することのできる
２−アミノインダンの製造方法を捉供することを目的と
する。The present invention produces 2-aminoindan only by reduction and distillation separation of 2-indanone oxime without going through 2-aminoindan hydrochloride, thereby significantly shortening the process and increasing the yield. The object of the present invention is to provide a method for producing 2-aminoindan that can improve the properties of 2-aminoindan.
〈課題を解決するための手段〉
本発明者らは、２−アミノインダンの製造方法としては
２−インダノンオキシムの還元によるのが最も有利であ
るという結論に至り、還元方法についての検討を行った
。 その結果、本反応においては生成するアミンおよび
水がニッケル触媒の活性ならびに選択性を低下せしめ、
そのために２−アミノインダンの収率が低下するという
ことを見出した。 従来法では水酸化ナトリウムなどを
添加することにより収率低下を抑制していたものと考え
られるが、そのために分離が複雑、かつ低収率となった
。 そこで触媒の活性を維持して反応収率の低下を抑え
、かつ分離を容易に行える方法について鋭意検討を行っ
た。 その結果、２−インダノンオキシムを還元する際
、ニッケル触媒を用いアルカリ土類金属の酸化物の存在
下において高圧水素化することにより、ジインダニルア
ミンがほとんど副生せず、２−アミノインダンを選択的
に合成できることを見出し、本発明を完成した。<Means for Solving the Problems> The present inventors came to the conclusion that reduction of 2-indanone oxime is the most advantageous method for producing 2-aminoindan, and conducted studies on reduction methods. Ta. As a result, in this reaction, the amine and water produced reduce the activity and selectivity of the nickel catalyst,
It has been found that the yield of 2-aminoindan decreases because of this. In the conventional method, it is thought that the decrease in yield was suppressed by adding sodium hydroxide or the like, but this made the separation complicated and resulted in a low yield. Therefore, we conducted extensive research on a method that would maintain the activity of the catalyst, suppress the drop in reaction yield, and facilitate separation. As a result, when reducing 2-indanone oxime, by high-pressure hydrogenation using a nickel catalyst in the presence of an alkaline earth metal oxide, almost no diindanylamine was produced, and 2-aminoindan was reduced. The present invention was completed based on the discovery that selective synthesis is possible.
すなわち、上記目的を達成するために本発明によれば、
下記式［Ｉ］に示す２−アミノインダンを製造するに際
し、下記式［ｎｌに示す２−インダノンオキシムを極性
溶媒中、アルカリ土類金属の酸化物の存在下においてニ
ッケル触媒を用いて高圧水素化することを特徴とする２
−アミノインダンの製造方法が提供される。That is, according to the present invention, in order to achieve the above object,
When producing the 2-aminoindan represented by the following formula [I], the 2-indanone oxime represented by the following formula [nl] was heated with high-pressure hydrogen using a nickel catalyst in a polar solvent in the presence of an alkaline earth metal oxide. 2 characterized by
- A method for producing aminoindan is provided.
（上記式中Ｒは、水素、低級アルキル基、低級アルコキ
シ基、またはハロゲンを示す。 ｎは０〜４までの整数
を示す。）
以下に本発明をさらに詳細に説明する。(R in the above formula represents hydrogen, a lower alkyl group, a lower alkoxy group, or a halogen. n represents an integer from 0 to 4.) The present invention will be explained in more detail below.
本発明の出発原料である２−インダノンオキシムは、下
記式［ＩＩ］で示される。2-indanone oxime, which is a starting material of the present invention, is represented by the following formula [II].
置換基Ｒは、水素、低級アルキル基、低級アルコキシ基
またはハロゲンを表す。The substituent R represents hydrogen, a lower alkyl group, a lower alkoxy group, or a halogen.
低級アルキル基としては、メチル基、エチル基、プロピ
ル基、ブチル基等が挙げられる。Examples of the lower alkyl group include a methyl group, an ethyl group, a propyl group, a butyl group, and the like.
低級アルコキシ基としては、メトキシ基、エトキシ基、
プロポキシ基、ブトキシ基等が挙げられる。Examples of lower alkoxy groups include methoxy group, ethoxy group,
Examples include propoxy group and butoxy group.
また、置換基Ｒは、特に存在していなくてもよく置換基
の数ｎはＯ〜４までの整数を示す。Further, the substituent R does not necessarily have to be present, and the number n of substituents is an integer from 0 to 4.
前記２−インダノンオキシムは、ＴｈｅＪｏｕｒｎａｌ
ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ、 Ｖｏ
ｌ、９． Ｐ、３８０−３９１． （１９４４）または
特開昭６０−２１８３６８号などに記述の方法により合
成することができるが、合成方法としてとくに規制はな
い。The 2-indanone oxime is described in The Journal
of Organic Chemistry, Vo
l, 9. P, 380-391. (1944) or JP-A No. 60-218368, etc., but there are no particular restrictions on the synthesis method.
２−インダノンオキシムは固体結晶であり還元反応は適
切な溶媒中で行う。 溶媒は２−インダノンオキシムを
溶解するものであればと（に制限はないが、好ましくは
オキシムに対して高い溶解性を示す極性の有機溶媒を用
いる。2-Indanone oxime is a solid crystal, and the reduction reaction is carried out in a suitable solvent. The solvent is not limited as long as it dissolves the 2-indanone oxime, but preferably a polar organic solvent exhibiting high solubility for the oxime is used.
たとえばメタノール、エタノールなどの低級アルコール
類、ジエチルエーテル、メチルエチルエーテルなどの低
級エーテル類、テトラヒドロフランまたはジオキサンな
どが挙げられる。Examples include lower alcohols such as methanol and ethanol, lower ethers such as diethyl ether and methyl ethyl ether, tetrahydrofuran, and dioxane.
あるいはこれらの任意の組合せによる混合溶媒でもよい
。 溶媒量は２−インダノンオキシムを溶解する範囲内
で選ばれるが、通常はオキシムに対して２〜１０容量倍
が適当である。Alternatively, a mixed solvent of any combination of these may be used. The amount of solvent is selected within a range that dissolves the 2-indanone oxime, but usually 2 to 10 times the volume of the oxime is appropriate.
触媒として用いるニッケルにはさまざまな種類のものが
あるが、ケイソウ土、シリカ、アルミナ、シリカ・アル
ミナなどを担体とした還元ニッケル触媒または該触媒を
還元後安定化したものが一般的に用いられる。 あるい
はラネーニッケル触媒も用いることができる。 触媒の
形状は粉末状、ベレット状、フレーク状のいずれでもよ
い。 また、銅、クロム、マンガンなどの酸化物を助触
媒として少量添加したものでもよい。 触媒量はニッケ
ル基準で２−インダノンオキシムに対して１〜５０重量
％、より好ましくは２〜２５重量％用いるのが適当であ
る。 ５０重量％を越えてもよいが、特に実質的な効果
は向上しない。 すなわち、５０重量％担持のニッケル
・ケイソウ土触媒であれば２〜１００重量％、より好ま
しくは５〜５０重量％が適当量であるといえる。 アル
カリ土類金属の酸化物としては酸化カルシウム、酸化マ
グネシウムなどが用いられる。There are various types of nickel used as catalysts, but generally used are reduced nickel catalysts with diatomaceous earth, silica, alumina, silica/alumina, etc. as carriers, or stabilized versions of such catalysts after reduction. Alternatively, a Raney nickel catalyst can also be used. The shape of the catalyst may be powder, pellet, or flake. Alternatively, a small amount of oxides such as copper, chromium, manganese, etc. may be added as a co-catalyst. The appropriate amount of the catalyst is 1 to 50% by weight, more preferably 2 to 25% by weight, based on nickel, based on the 2-indanone oxime. Although it may exceed 50% by weight, the substantial effect is not particularly improved. That is, in the case of a 50% by weight nickel/diatomaceous earth catalyst, an appropriate amount is 2 to 100% by weight, more preferably 5 to 50% by weight. Calcium oxide, magnesium oxide, etc. are used as the alkaline earth metal oxide.
アルカリ土類金属の酸化物の作用は、反応で副生ずる水
を除去することにより触媒の活性および選択性の低下を
抑えることにある。 ２−インダノンオキシムの還元
では反応の過程で副生ずる水が触媒の活性を低下せしめ
、２−アミノインダンの収率低下の原因となる。 反応
系にアルカリ土類金属の酸化物を、より好ましくは仕込
みの直前に粉末状としたものを添加すると、脱水作用に
より触媒活性が反応終了まで維持されるため２−アミノ
インダンが高収率で得られる。 アルカリ土類金属の酸
化物の添加量は２−インダノンオキシムに対して０１〜
２．０モル％の範囲内で選ばれるが、より好ましくは０
．８〜・１．２モル％が適当である。The function of the alkaline earth metal oxide is to suppress the decrease in catalyst activity and selectivity by removing water produced by-product in the reaction. In the reduction of 2-indanone oxime, water by-produced during the reaction process reduces the activity of the catalyst, causing a decrease in the yield of 2-aminoindan. When an alkaline earth metal oxide, preferably a powdered one, is added to the reaction system immediately before charging, the catalytic activity is maintained until the end of the reaction due to the dehydration effect, resulting in a high yield of 2-aminoindan. can get. The amount of alkaline earth metal oxide added is 01 to 2-indanone oxime.
Selected within the range of 2.0 mol%, more preferably 0
．． A suitable amount is 8 to 1.2 mol%.
水素圧力も２−アミノインダンの収率に大きな影響を与
える因子である。 たとえば水素圧力が低すぎると触媒
表面に水素が十分な速度で供給されず、主反応の水素化
が進行しにくくなる。 また圧力が高すぎると芳香核水
素化などの副反応が進行するようになる。 水素圧力は
３０〜２００ ｋｇｆ／ｃｍ２Ｇ、より好ましくは５０
〜１５０ ｋｇｆ／ｃｍ２Ｇが適当である。Hydrogen pressure is also a factor that greatly affects the yield of 2-aminoindan. For example, if the hydrogen pressure is too low, hydrogen will not be supplied to the catalyst surface at a sufficient rate, making it difficult for the main reaction to proceed with hydrogenation. Furthermore, if the pressure is too high, side reactions such as aromatic nuclear hydrogenation will proceed. Hydrogen pressure is 30 to 200 kgf/cm2G, more preferably 50
~150 kgf/cm2G is appropriate.
反応温度は触媒が活性を示す温度範囲で選ばれ、担持ニ
ッケル触媒では８０℃以上、ラネーニッケルでは３０℃
以上であればよいが、１６０℃になると２−インダノン
オキシムが分解することがあるので好ましくない。 本
反応では、担持ニッケル触媒を用いた場合１２０〜１４
０℃、ラネーニッケルを用いた場合５０〜１００℃が適
当な反応温度である。The reaction temperature is selected within the temperature range where the catalyst is active, 80°C or higher for supported nickel catalysts and 30°C for Raney nickel.
It is acceptable if the temperature is above 160°C, but it is not preferable because 2-indanone oxime may decompose at a temperature of 160°C. In this reaction, when using a supported nickel catalyst, 120 to 14
Suitable reaction temperatures are 0°C and 50 to 100°C when Raney nickel is used.
以上の条件で１０分〜３時間、より好ましくは３０分〜
２時間還元反応を行うと水素消費が停止しその時点で反
応工程を終了することができる。Under the above conditions, 10 minutes to 3 hours, more preferably 30 minutes to
When the reduction reaction is carried out for 2 hours, hydrogen consumption stops and the reaction process can be completed at that point.
この反応によって生成される２〜アミノインダンは、下
記式［Ｉ］で示される。The 2-aminoindan produced by this reaction is represented by the following formula [I].
置換基Ｒは、水素、低級アルキル基、低級アルコキシ基
またはハロゲンを表し、これら置換基の詳細については
２−インダノンオキシム式［ｎｌ と同様である。The substituent R represents hydrogen, a lower alkyl group, a lower alkoxy group, or a halogen, and details of these substituents are the same as in the 2-indanone oxime formula [nl.
また、これら置換基の数ｎはＯ〜４までの整数であれば
よい。Further, the number n of these substituents may be an integer from 0 to 4.
なお、反応装置はステンレス製、耐圧ガラス製、または
ステンレスにガラスやテフロンなどのライニングを施し
たオートクレーブなどを用いるのが一般的であるが、構
造・様式などでとくに規制はない。The reaction apparatus is generally made of stainless steel, pressure-resistant glass, or an autoclave made of stainless steel lined with glass or Teflon, but there are no particular restrictions on structure or style.
反応終了後は、触媒およびアルカリ土類金属の酸化物を
濾過あるいは沈降などの方法で分離したのちに濾液ある
いは上澄み液を蒸留する。After the reaction is completed, the catalyst and the alkaline earth metal oxide are separated by filtration or sedimentation, and then the filtrate or supernatant liquid is distilled.
この際、触媒およびアルカリ土類金属の酸化物の分離工
程を省略して、直接蒸留する方法も可能である。 ただ
しこれらは分離・回収して再利用に供されるのが一般的
である。 蒸留の際は直接精留操作を行う方法でも、あ
るいは半熱留塔により溶媒を除いたのちに精留操作を行
う方法でもよい。 いずれの場合も高純度（９９ｗｔ％
以上）の２−アミノインダンが高収率で得られる。At this time, it is also possible to omit the step of separating the catalyst and the alkaline earth metal oxide and directly distill it. However, these are generally separated and recovered for reuse. In the case of distillation, a method may be employed in which a direct rectification operation is performed, or a method in which a rectification operation is performed after removing the solvent using a semi-thermal distillation column. In both cases, high purity (99wt%
The above 2-aminoindan can be obtained in high yield.
〈実施例〉
以下に本発明を実施例に基づいてさらに具体的に説明す
るが、本発明はこれらの条件によって限定されるもので
はない。<Examples> The present invention will be described in more detail below based on Examples, but the present invention is not limited by these conditions.
（実施例１）
２−インダノンオキシム１４７ｇ （１，００ｍｏｌ）
、ニッケル・ケイソウ土（Ｎｉ担持Ｉ’＋５０ｗｔ％）
１２．０ｇ、エタノール５００ｇ、酸化カルシウム５０
．ｏｇを内容積１．５℃のステンレス（ＳＵＳ３１６）
製オートクレーブに仕込み、オートクレーブ内を窒素ガ
スで置換したのち、水素を８０ ｋｇｆ／ｃｍ”Ｇの圧
力で充填した。 攪拌状態で１３０℃に昇温後、１時間
反応を行った。(Example 1) 2-indanone oxime 147g (1,00mol)
, nickel diatomaceous earth (Ni supported I'+50wt%)
12.0g, ethanol 500g, calcium oxide 50
．． Stainless steel (SUS316) with an internal volume of 1.5℃
After replacing the inside of the autoclave with nitrogen gas, it was filled with hydrogen at a pressure of 80 kgf/cm''G. After raising the temperature to 130°C with stirring, the reaction was carried out for 1 hour.
オートクレーブを冷却して水素の残ガスを放出した後、
反応生成液を抜き比した。 この反応液中に存在する２
−アミノインダンは、ガスクロマトグラフィーによる定
量の結果、１２０ｇ （０，９０ｍｏｌ）であった。After cooling the autoclave and releasing the residual hydrogen gas,
The reaction product solution was extracted and compared. 2 present in this reaction solution
-Aminoindan was determined to be 120 g (0.90 mol) by gas chromatography.
反応液を濾過してニッケル・ケイソウ土、酸化カルシウ
ムを除去し５たのち、蒸留によりエタノールを除去した
。 次に、精留装置を用いて減圧蒸留を行い、２−アミ
ノインダンを留出させ分離した。 純度９９％の２−ア
ミノインダンが１１５ｇ （０，８６ｍｏ １）得られ
た。The reaction solution was filtered to remove nickel diatomaceous earth and calcium oxide, and then ethanol was removed by distillation. Next, vacuum distillation was performed using a rectifier to distill and separate 2-aminoindan. 115 g (0.86 mo 1) of 2-aminoindan with a purity of 99% was obtained.
（実施例２）
溶媒としてエタノールのがわりにメタノール５００ｇ用
いたほかは実施例１と同様の操作を行った。 純度９９
％の２−アミノインダンが１１２ｇ （０，８４ｍｏｌ
）得られた。(Example 2) The same operation as in Example 1 was performed except that 500 g of methanol was used instead of ethanol as the solvent. Purity 99
% 2-aminoindan 112g (0.84mol
) obtained.
（実施例３）
溶媒としてエタノールのかわりにテトラヒドロフランを
５００ｇ用いたほかは実施例１と同様の操作を行った。(Example 3) The same operation as in Example 1 was performed except that 500 g of tetrahydrofuran was used instead of ethanol as the solvent.
純度９９％の２−アミノインダンが１０７ｇ （０，
８０ｍｏｌ）得られた。107g of 2-aminoindan with a purity of 99% (0,
80 mol) was obtained.
（実施例４）
触媒としてニッケル・ケイソウ士のかわりにニッケル・
シリカ・アルミナを用いたほかは実施例１と同様の操作
を行った。 純度９９％の２−アミノインダンが１０９
ｇ（０，８２ｍｏｌ）得られた。(Example 4) Using nickel as a catalyst instead of nickel diatomaceous material
The same operation as in Example 1 was performed except that silica/alumina was used. 2-aminoindan with 99% purity is 109
g (0.82 mol) was obtained.
（比較例１）
酸化カルシウムのかわりにナトリウムメチラート５４．
０ｇを用いたほかは実施例１と同様の操作を反応工程ま
で行った。 反応液中の２−アミノインダン含有量はガ
スクロマトグラフィーによる定量の結果９３．０ｇ （
０，７０ｍ０１）であった。(Comparative Example 1) Sodium methylate instead of calcium oxide 54.
The same operation as in Example 1 was performed up to the reaction step except that 0 g was used. The content of 2-aminoindan in the reaction solution was determined by gas chromatography and was 93.0 g (
0.70m01).
（比較例２）
触媒としてニッケル・ケイソウ士のかわりに５％−パラ
ジウムカーボン１２、Ｏｇを用いたほかは、実施例１と
同様の操作を反応工程まで行った。 反応液中の２−ア
ミノインダン含有量はガスクロマトゲフィーによる定量
の結果２０．０ｇ （０，１５ｍｏｌ）であった。(Comparative Example 2) The same operation as in Example 1 was performed up to the reaction step, except that 5%-palladium carbon 12, Og was used instead of nickel diatomaceous material as a catalyst. The content of 2-aminoindan in the reaction solution was determined by gas chromatography to be 20.0 g (0.15 mol).
〈発明の効果〉
本発明は、以上説明したように構成されているので、本
発明の方法によれば、還元時に用いる触媒・溶媒・添加
物が遊離の２−アミノインゲンと容易に分離することが
でき、従来より高い収率で、かつ経済的に２−アミノイ
ンダンを製造することができる。<Effects of the Invention> Since the present invention is configured as explained above, according to the method of the present invention, the catalyst, solvent, and additives used during reduction can be easily separated from free 2-aminoin bean. 2-aminoindan can be produced economically with a higher yield than conventional methods.
Claims (1)
するに際し、下記式［II］に示す２−インダノンオキシ
ムを極性溶媒中、アルカリ土類金属の酸化物の存在下に
おいてニッケル触媒を用いて高圧水素化することを特徴
とする２−アミノインダンの製造方法。 式［ I ］▲数式、化学式、表等があります▼ 式［II］▲数式、化学式、表等があります▼ （上記式中Ｒは、水素、低級アルキル基、低級アルコキ
シ基、またはハロゲンを示す。ｎは０〜４までの整数を
示す。）(1) When producing 2-aminoindan shown in the following formula [I], 2-indanone oxime shown in the following formula [II] is heated with a nickel catalyst in the presence of an alkaline earth metal oxide in a polar solvent. 1. A method for producing 2-aminoindan, which comprises high-pressure hydrogenation using 2-aminoindan. Formula [I] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ Formula [II] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the above formula, R represents hydrogen, a lower alkyl group, a lower alkoxy group, or a halogen. n indicates an integer from 0 to 4.)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2172235A JPH0466558A (en) | 1990-06-29 | 1990-06-29 | Production of 2-aminoindane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2172235A JPH0466558A (en) | 1990-06-29 | 1990-06-29 | Production of 2-aminoindane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0466558A true JPH0466558A (en) | 1992-03-02 |
Family
ID=15938120
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2172235A Pending JPH0466558A (en) | 1990-06-29 | 1990-06-29 | Production of 2-aminoindane |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0466558A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8012231B2 (en) | 2003-04-16 | 2011-09-06 | Horiba, Ltd. | Particulate matter analyzer, collecting filter and system for analyzing and collecting samples from fluids |
-
1990
- 1990-06-29 JP JP2172235A patent/JPH0466558A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8012231B2 (en) | 2003-04-16 | 2011-09-06 | Horiba, Ltd. | Particulate matter analyzer, collecting filter and system for analyzing and collecting samples from fluids |
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