KR102592383B1 - Diamine compound and method for producing intermediate thereof - Google Patents

Diamine compound and method for producing intermediate thereof Download PDF

Info

Publication number
KR102592383B1
KR102592383B1 KR1020177027754A KR20177027754A KR102592383B1 KR 102592383 B1 KR102592383 B1 KR 102592383B1 KR 1020177027754 A KR1020177027754 A KR 1020177027754A KR 20177027754 A KR20177027754 A KR 20177027754A KR 102592383 B1 KR102592383 B1 KR 102592383B1
Authority
KR
South Korea
Prior art keywords
formula
piperidine
reaction
nitrophenyl
production method
Prior art date
Application number
KR1020177027754A
Other languages
Korean (ko)
Other versions
KR20170127495A (en
Inventor
겐지 다카세
요시미치 모리모토
Original Assignee
닛산 가가쿠 가부시키가이샤
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 닛산 가가쿠 가부시키가이샤 filed Critical 닛산 가가쿠 가부시키가이샤
Publication of KR20170127495A publication Critical patent/KR20170127495A/en
Application granted granted Critical
Publication of KR102592383B1 publication Critical patent/KR102592383B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/26—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
    • C08G73/06—Polycondensates having nitrogen-containing heterocyclic rings in the main chain of the macromolecule
    • C08G73/10—Polyimides; Polyester-imides; Polyamide-imides; Polyamide acids or similar polyimide precursors
    • C08G73/1003—Preparatory processes
    • C08G73/1007—Preparatory processes from tetracarboxylic acids or derivatives and diamines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K19/00—Liquid crystal materials
    • C09K19/52—Liquid crystal materials characterised by components which are not liquid crystals, e.g. additives with special physical aspect: solvents, solid particles
    • C09K19/54—Additives having no specific mesophase characterised by their chemical composition
    • C09K19/56—Aligning agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B61/00—Other general methods

Abstract

액정 배향막을 제작하기 위한 폴리이미드계 중합체의 원료 등으로서 유용한 디아민 화합물 및 그 중간체의 신규한 제조 방법을 제공한다.
p-플루오로니트로벤젠 (D) 과 4-(아미노메틸)피페리딘 (E) 을, 디메틸아세트아미드, 1,3-디메틸-2-이미다졸리디논, 디메틸술폭사이드 및 N-메틸피롤리돈으로 이루어지는 군에서 선택되는 용매 중에서 반응시켜 식 (C) 로 나타내는 화합물을 얻는다. 이 화합물의 아미노기를 터셔리부틸옥시카르보닐화함으로써, 식 (B) 로 나타내는 화합물을 얻는다. 또한, 이 화합물을 환원하여 식 (A) 로 나타내는 화합물을 얻는다.
A novel manufacturing method of a diamine compound and an intermediate thereof useful as a raw material for a polyimide polymer for producing a liquid crystal alignment film is provided.
p-fluoronitrobenzene (D) and 4-(aminomethyl)piperidine (E), dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, dimethylsulfoxide and N-methylpyrroli The compound represented by formula (C) is obtained by reacting in a solvent selected from the group consisting of money. By tertiary butyloxycarbonylation of the amino group of this compound, the compound represented by formula (B) is obtained. Additionally, this compound is reduced to obtain a compound represented by formula (A).

Description

디아민 화합물 및 그 중간체의 제조 방법 {DIAMINE COMPOUND AND METHOD FOR PRODUCING INTERMEDIATE THEREOF}Method for producing diamine compounds and intermediates thereof {DIAMINE COMPOUND AND METHOD FOR PRODUCING INTERMEDIATE THEREOF}

본 발명은, 액정 배향막을 제작하기 위한 폴리이미드계 중합체의 원료 등으로서 유용한 디아민 화합물 및 그 중간체의 신규한 제조 방법에 관한 것이다.The present invention relates to a novel manufacturing method of a diamine compound useful as a raw material for a polyimide-based polymer for producing a liquid crystal alignment film, and an intermediate thereof.

현재, 액정 표시 소자에 사용되는 액정 배향막에는, 많은 경우, 폴리이미드막이 사용되고 있고, 폴리이미드막의 액정 배향막은, 폴리이미드의 전구체인 폴리아믹산의 용액, 또는 용매에 가용성이 있는 폴리이미드의 용액을 기판에 도포하고, 소성하여, 얻어지는 막을 러빙 처리 등의 배향 처리하는 방법에 의해 제작되고 있다 (특허문헌 1, 2 를 참조).Currently, in many cases, a polyimide film is used for the liquid crystal alignment film used in a liquid crystal display element, and the liquid crystal alignment film of the polyimide film uses a solution of polyamic acid, which is a precursor of polyimide, or a solution of polyimide soluble in a solvent as a substrate. It is produced by applying a film to a film, baking it, and subjecting the resulting film to an orientation treatment such as a rubbing treatment (see Patent Documents 1 and 2).

이 폴리아믹산이나 폴리이미드는, 일반적으로, 테트라카르복실산 2수화물 등의 테트라카르복실산 유도체와 디아민의 축중합 반응에 의해 제조되고 있다.These polyamic acids and polyimides are generally manufactured by a condensation polymerization reaction of tetracarboxylic acid derivatives such as tetracarboxylic acid dihydrate and diamine.

이러한 폴리아믹산이나 폴리이미드 등의 원료인 디아민은, 이것으로부터 얻어지는 액정 배향막의 특성, 즉, 액정 표시 소자의 특성에 영향을 미치므로 중요하여, 종래부터 여러 가지 디아민 화합물이 사용되고, 제안되고 있다.Diamine, which is a raw material such as polyamic acid or polyimide, is important because it affects the characteristics of the liquid crystal alignment film obtained therefrom, that is, the characteristics of the liquid crystal display element, and various diamine compounds have been used and proposed conventionally.

일본 공개특허공보 평7-120769호Japanese Patent Publication No. 7-120769 일본 공개특허공보 평9-146100호Japanese Patent Publication No. 9-146100

본 발명자들은, 러빙법, 혹은 광 배향법으로 배향 처리해도, 전압 유지율이 높고, 액정의 배향성이 우수하며, 직류 전압에 의해 축적되는 잔류 전하가 적은 액정 배향막이 얻어지는 폴리아믹산이나 폴리이미드의 원료인 디아민 화합물로서, 하기의 식 (A) 로 나타내는 디아민을 알아내었다.The present inventors have developed a polyamic acid or polyimide raw material from which a liquid crystal alignment film with high voltage retention, excellent liquid crystal orientation, and low residual charge accumulated by direct current voltage can be obtained even if the alignment treatment is performed by a rubbing method or a photo-alignment method. As a diamine compound, diamine represented by the following formula (A) was found.

[화학식 1][Formula 1]

Figure 112017095275022-pct00001
Figure 112017095275022-pct00001

상기 디아민 화합물의 제조 방법으로서, 본 발명자들은, p-플루오로니트로벤젠과, 4-(아미노메틸)피페리딘을 반응시켜 디니트로 화합물을 제조하고, 터셔리부톡시카르보닐화에 제공한 후, 환원한다는 방법을 고안하여 실시하였다.As a method for producing the diamine compound, the present inventors reacted p-fluoronitrobenzene and 4-(aminomethyl)piperidine to prepare a dinitro compound, and then subjected to tertiary butoxycarbonylation. , a method of reduction was devised and implemented.

그러나, 이 제조 방법을 실시해 보면, 각 전 (前) 공정에서 얻어지는 상기 디아민 화합물의 중간체를 생성하고, 이것을 단리하고자 하는 경우, 그것에 의해 수율이 저하된다. 또, p-플루오로니트로벤젠과 4-(아미노메틸)피페리딘의 반응시, 당해 반응의 일반적인 조건인, 탄산칼륨의 존재 하에 용매로서, DMF (N,N-디메틸포름아미드) 등의 통상적인 용매를 사용한 경우에는, 불소 원자가 DMF 에서 유래하는 디메틸아미노기와 치환 반응하여, p-니트로-N,N-디메틸아닐린이 부생하여, 더욱 수율을 저하시킨다는 문제가 있었다.However, when this production method is implemented, an intermediate of the diamine compound obtained in each previous step is produced, and when this is attempted to be isolated, the yield decreases. In addition, during the reaction of p-fluoronitrobenzene and 4-(aminomethyl)piperidine, in the presence of potassium carbonate, which is the general condition for the reaction, as a solvent, conventional solvents such as DMF (N,N-dimethylformamide) are used. When a phosphorus solvent was used, there was a problem in that the fluorine atom underwent a substitution reaction with the dimethylamino group derived from DMF, forming p-nitro-N,N-dimethylaniline as a by-product, further reducing the yield.

본 발명은, 상기 문제를 해결함과 함께, 반응 속도가 높아, 용적 효율이 높고, 부생물이 적어, 고순도이며, 또한 중간체를 단리할 필요가 없어 고수율이고, 상기 식 (A) 로 나타내는 디아민 화합물 및 그 중간체를 제조하는 방법을 제공하는 것을 목적으로 한다.In addition to solving the above problems, the present invention has a high reaction rate, high volumetric efficiency, few by-products, high purity, and high yield without the need to isolate intermediates, and provides diamine represented by the formula (A) The purpose is to provide a method for producing compounds and intermediates thereof.

본 발명자들은, 상기의 상황을 감안하여, 예의 검토한 결과, 상기 목적을 달성할 수 있는 상기 식 (A) 로 나타내는 디아민 화합물 및 그 중간체를 제조하는 방법을 알아내어, 본 발명의 완성에 이르렀다.As a result of intensive studies in consideration of the above-mentioned situation, the present inventors discovered a method for producing a diamine compound represented by the above-mentioned formula (A) and an intermediate thereof that can achieve the above-described object, and achieved completion of the present invention.

즉, 본 발명은, 하기를 요지로 하는 것이다.That is, the present invention has the following as a gist.

1. p-플루오로니트로벤젠과 4-(아미노메틸)피페리딘을, 디메틸아세트아미드, 1,3-디메틸-2-이미다졸리디논, 디메틸술폭사이드 및 N-메틸피롤리돈으로 이루어지는 군에서 선택되는 적어도 1 종의 용매 중에서 반응시키는, 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 의 제조 방법.1. A group consisting of p-fluoronitrobenzene and 4-(aminomethyl)piperidine, dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and N-methylpyrrolidone. A method for producing 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C), comprising reacting in at least one solvent selected from the following.

[화학식 2][Formula 2]

Figure 112017095275022-pct00002
Figure 112017095275022-pct00002

2. 염기의 존재 하에 반응시키는 상기 1 에 기재된 제조 방법.2. The production method according to 1 above, wherein the reaction is carried out in the presence of a base.

3. 4-(아미노메틸)피페리딘 1 몰에 대해, p-플루오로니트로벤젠을 2 ∼ 10 몰 반응시키는 상기 1 또는 2 에 기재된 제조 방법.3. The production method according to 1 or 2 above, wherein 2 to 10 moles of p-fluoronitrobenzene are reacted with respect to 1 mole of 4-(aminomethyl)piperidine.

4. 상기 용매가, N-메틸피롤리돈인 상기 1 ∼ 3 중 어느 하나에 기재된 제조 방법.4. The production method according to any one of 1 to 3 above, wherein the solvent is N-methylpyrrolidone.

5. 상기 1 ∼ 3 중 어느 하나에서 얻어지는 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 을 터셔리부틸옥시카르보닐화하는, 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 의 제조 방법.5. 4-(N-p), wherein 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C) obtained in any one of 1 to 3 above is tert-butyloxycarbonylated. Method for producing -nitrophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B).

[화학식 3][Formula 3]

Figure 112017095275022-pct00003
Figure 112017095275022-pct00003

6. 상기 터셔리부틸옥시카르보닐화를 염기의 존재 하에서 실시하는 상기 5 에 기재된 제조 방법.6. The production method according to 5 above, wherein the tertiary butyloxycarbonylation is carried out in the presence of a base.

7. 상기 터셔리부틸옥시카르보닐화제의 사용량이 식 (C) 로 나타내는 화합물 1 몰에 대해 1 ∼ 10 몰인 상기 5 또는 6 에 기재된 제조 방법.7. The production method according to 5 or 6 above, wherein the amount of the tertiary-butyloxycarbonylating agent used is 1 to 10 moles per 1 mole of the compound represented by formula (C).

8. 상기 터셔리부틸옥시카르보닐화를 테트라하이드로푸란의 용매 중 실시하는 상기 5 ∼ 7 중 어느 하나에 기재된 제조 방법.8. The production method according to any one of 5 to 7 above, wherein the tertiary butyloxycarbonylation is carried out in a tetrahydrofuran solvent.

9. 상기 5 ∼ 8 중 어느 하나에서 얻어지는 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 을 환원하는, 4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘 (A) 의 제조 방법.9. Reducing 4-(N-p-nitrophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B) obtained in any one of 5 to 8 above, 4 Method for producing -(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine (A).

[화학식 4][Formula 4]

Figure 112017095275022-pct00004
Figure 112017095275022-pct00004

10. 촉매의 존재 하에 있어서의 수소 첨가 반응에 의해 환원하는 상기 9 에 기재된 제조 방법.10. The production method according to item 9 above, which involves reduction by hydrogenation reaction in the presence of a catalyst.

11. 활성탄 담지 촉매의 존재 하에 환원하는 상기 9 또는 10 에 기재된 제조 방법.11. The production method according to item 9 or 10 above, wherein reduction is carried out in the presence of an activated carbon supported catalyst.

본 발명에 의하면, 반응 속도가 높아, 용적 효율이 높고, 부생물이 적어, 고순도이며, 또한 중간체를 단리할 필요가 없어 고수율이고, 폴리이미드 전구체 혹은 폴리이미드의 제조의 원료로서 유용한, 상기 식 (A) 로 나타내는 디아민 화합물, 및 그 중간체를 제조하는 방법이 제공된다.According to the present invention, the reaction rate is high, the volumetric efficiency is high, there are few by-products, high purity, there is no need to isolate intermediates, high yield, and the above formula is useful as a polyimide precursor or raw material for the production of polyimide. A method for producing a diamine compound represented by (A) and an intermediate thereof is provided.

이하, 본 발명을 상세하게 설명한다.Hereinafter, the present invention will be described in detail.

본 발명에서는, p-플루오로니트로벤젠 (D) 과 4-(아미노메틸)피페리딘 (E) 을 반응시킴으로써, 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 이 얻어진다.In the present invention, 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)pi is obtained by reacting p-fluoronitrobenzene (D) with 4-(aminomethyl)piperidine (E). Peridine (C) is obtained.

[화학식 5][Formula 5]

Figure 112017095275022-pct00005
Figure 112017095275022-pct00005

상기 반응에 있어서, 4-(아미노메틸)피페리딘 (E) 과 p-플루오로니트로벤젠 (D) 의 사용 비율은, 전자 1 몰에 대해, 후자가, 바람직하게는 2 ∼ 10 몰이고, 중간체의 잔존이나 과잉 반응물의 생성을 억제하는 관점에서, 보다 바람직하게는 2.0 ∼ 2.2 몰이다.In the above reaction, the ratio of 4-(aminomethyl)piperidine (E) and p-fluoronitrobenzene (D) used is preferably 2 to 10 moles of the latter per 1 mole of the former, From the viewpoint of suppressing the remaining intermediates and the production of excess reactants, the amount is more preferably 2.0 to 2.2 mol.

상기 반응에 있어서, 출발 원료로서 사용하는 p-플루오로니트로벤젠, 및 4-(아미노메틸)피페리딘은 시판품으로서 입수할 수 있다. 또한, 본 발명에서는, p-플루오로니트로벤젠의 벤젠 고리는, 메틸기 등의 치환기를 단수 혹은 복수 가지고 있어도 된다.In the above reaction, p-fluoronitrobenzene and 4-(aminomethyl)piperidine used as starting materials are commercially available. In addition, in the present invention, the benzene ring of p-fluoronitrobenzene may have one or more substituents such as a methyl group.

반응 형식은, 회전식 (배치식), 유통식 중 어느 것이어도 되지만, 조작성의 관점에서, 배치식이 바람직하다.The reaction format may be either a rotational (batch) or a distribution type, but the batch type is preferable from the viewpoint of operability.

반응은, 염기 존재 하에서 실시하는 것이 바람직하다. 염기로는, 예를 들어, 수산화나트륨, 수산화칼륨 등의 알칼리 금속 수산화물, 탄산나트륨, 탄산칼륨 등의 알칼리 금속 탄산염, 탄산수소나트륨, 탄산수소칼륨 등의 알칼리 금속 중탄산염, 인산칼륨, 1,8-디아자비시클로[5,4,0]-7-운데센 등의 유기 염기 등을 사용할 수 있다.The reaction is preferably carried out in the presence of a base. Examples of bases include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate, potassium phosphate, and 1,8-dia. Organic bases such as zavicyclo[5,4,0]-7-undecene can be used.

그 중에서도, 탄산나트륨, 탄산칼륨 등의 알칼리 금속 탄산염이 바람직하다. 특히, 미 (微) 분말 탄산칼륨을 사용하면, 반응성이 향상되므로 바람직하다. 시판되고 있는 미분말 탄산칼륨으로는, FG-F20 (아사히 가라스사 상품명) 등을 들 수 있다.Among them, alkali metal carbonates such as sodium carbonate and potassium carbonate are preferable. In particular, it is preferable to use finely powdered potassium carbonate because it improves reactivity. Examples of commercially available fine powder potassium carbonate include FG-F20 (Asahi Glass brand name).

염기의 사용량은, 4-(아미노메틸)피페리딘 (E) 에 대해 1 ∼ 4 당량, 바람직하게는 1.0 ∼ 1.5 당량 사용할 수 있다.The amount of base used can be 1 to 4 equivalents, preferably 1.0 to 1.5 equivalents, based on 4-(aminomethyl)piperidine (E).

반응 용매로는, 디메틸아세트아미드 (DMAc), 1,3-디메틸-2-이미다졸리디논 (DMI), 디메틸술폭사이드 (DMSO), 및 N-메틸피롤리돈 (NMP) 으로 이루어지는 군에서 선택되는 적어도 1 종이 사용된다. 그 중에서도, N-메틸피롤리돈이 특히 바람직하다.The reaction solvent is selected from the group consisting of dimethylacetamide (DMAc), 1,3-dimethyl-2-imidazolidinone (DMI), dimethyl sulfoxide (DMSO), and N-methylpyrrolidone (NMP). At least one species is used. Among them, N-methylpyrrolidone is particularly preferable.

이들 용매를 사용한 경우, 반응 종료 후에, 반응 용액을 그대로, 다음의 Boc 공정에서 사용할 수 있는 점에서, 제조 상으로도 유리하다.When these solvents are used, it is also advantageous in terms of production because, after completion of the reaction, the reaction solution can be used as is in the next Boc process.

용매의 사용량은, 특별히 한정되지 않지만, 식 (C) 로 나타내는 화합물 1 질량부에 대해, 1 ∼ 10 질량배의 용매를 사용하는 것이 바람직하다. 보다 바람직하게는, 3 ∼ 5 질량배이고, 더욱 바람직하게는 3.1 ∼ 3.3 질량배이다.The amount of solvent used is not particularly limited, but it is preferable to use 1 to 10 times by mass of the solvent relative to 1 part by mass of the compound represented by formula (C). More preferably, it is 3 to 5 times by mass, and even more preferably, it is 3.1 to 3.3 times by mass.

반응 온도는, 예를 들어, -10 ∼ 200 ℃, 바람직하게는 40 ∼ 100 ℃ 이다. 반응 시간은, 배치 처리의 경우에는, 0.5 ∼ 20 시간, 바람직하게는 1 ∼ 15 시간이다.The reaction temperature is, for example, -10 to 200°C, preferably 40 to 100°C. In the case of batch processing, the reaction time is 0.5 to 20 hours, preferably 1 to 15 hours.

본 발명에서는, 상기 반응에서 얻어진 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 을 함유하는 반응 용액을 터셔리부틸옥시카르보닐화함으로써, 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 이 얻어진다. 본 발명에서는, 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘을 단리하지 않고, 이것을 함유하는 반응 용액을 그대로 다음 공정에 사용할 수 있어, 반응 효율의 향상이나 수율의 향상 등의 점에서 유리하다.In the present invention, the reaction solution containing 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C) obtained in the above reaction is tert-butyloxycarbonylated, thereby producing 4- (N-p-nitrophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B) is obtained. In the present invention, 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine is not isolated, and the reaction solution containing it can be used as is in the next step, improving reaction efficiency and It is advantageous in terms of improving yield, etc.

[화학식 6][Formula 6]

Figure 112017095275022-pct00006
Figure 112017095275022-pct00006

상기의 반응에서는, 화합물 (C) 1 몰에 대해, 이탄산디-tert-부틸 (Boc2O) 등의 터셔리부틸옥시카르보닐화제를, 바람직하게는 1 ∼ 5 몰, 바람직하게는 1.3 ∼ 2.5 몰 사용하는 것이 바람직하고, 이러한 사용량에 의해, 이탄산디-tert-부틸 (Boc 기라고도 한다) 의 도입 수를 제어할 수 있다.In the above reaction, the amount of tert-tert-butyloxycarbonylating agent such as di-tert-butyl carbonate (Boc 2 O) is preferably 1 to 5 mol, preferably 1.3 to 2.5 mol, per 1 mol of compound (C). It is preferable to use it by mole, and by using this amount, the number of introduction of di-tert-butyl bicarbonate (also called Boc group) can be controlled.

터셔리부틸옥시카르보닐화제로는, N-tert-부톡시카르보닐이미다졸, 탄산 tert-부틸페닐, 카르바진산tert-부틸, 클로로포름산tert-부틸, 이탄산디-tert-부틸 등을 들 수 있고, 특히 바람직한 것은 이탄산디-tert-부틸이다.Examples of tert-butyloxycarbonylating agents include N-tert-butoxycarbonylimidazole, tert-butylphenyl carbonate, tert-butyl carbazic acid, tert-butyl chloroformate, and di-tert-butyl bicarbonate. may be used, and particularly preferred is di-tert-butyl bicarbonate.

상기 반응에 있어서 염기의 존재는, 반드시 필요한 것은 아니지만, 염기를 사용하는 경우, 예를 들어, 수산화나트륨, 수산화칼륨, 수산화리튬, 탄산수소나트륨, 탄산수소칼륨, 인산칼륨, 탄산나트륨, 탄산칼륨, 탄산리튬, 탄산세슘 등의 무기 염기 ; 트리메틸아민, 트리에틸아민, 트리프로필아민, 트리이소프로필아민, 트리부틸아민, 디이소프로필에틸아민, 피리딘, N,N-디메틸-4-아미노피리딘, 이미다졸, 퀴놀린, 콜리딘 등의 아민류 ; 수소화나트륨, 수소화칼륨, tert-부톡시나트륨, tert-부톡시칼륨 등의 염기 ; 등을 사용할 수 있다. 그 중에서도, N,N-디메틸-4-아미노피리딘 (DMAP) 이 바람직하다.The presence of a base in the above reaction is not absolutely necessary, but when a base is used, for example, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium bicarbonate, potassium bicarbonate, potassium phosphate, sodium carbonate, potassium carbonate, carbonic acid. Inorganic bases such as lithium and cesium carbonate; Amines such as trimethylamine, triethylamine, tripropylamine, triisopropylamine, tributylamine, diisopropylethylamine, pyridine, N,N-dimethyl-4-aminopyridine, imidazole, quinoline, and collidine; Bases such as sodium hydride, potassium hydride, sodium tert-butoxy, and potassium tert-butoxy; etc. can be used. Among them, N,N-dimethyl-4-aminopyridine (DMAP) is preferable.

염기의 사용량은, 상기 식 (C) 로 나타내는 화합물에 대해, 바람직하게는 0.01 ∼ 5.0 당량, 보다 바람직하게는 0.01 ∼ 0.10 당량이다.The amount of base used is preferably 0.01 to 5.0 equivalents, more preferably 0.01 to 0.10 equivalents, relative to the compound represented by the formula (C).

4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘을, 터셔리부틸옥시카르보닐화제와 반응시킬 때의 용매는, 각 원료와 반응하지 않는 용매이면 사용할 수 있다.When reacting 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine with a tertiary butyloxycarbonylating agent, any solvent that does not react with each raw material can be used. .

예를 들어, 비프로톤성 극성 유기 용매 (디메틸포름아미드 (DMF), DMSO, DMAc, NMP 등) ; 에테르류 (디에틸에테르 (Et2O), 디이소프로필에테르 (i-Pr2O), 터셔리부틸메틸에테르 (TBME), 시클로펜틸메틸에테르 (CPME), 테트라하이드로푸란 (THF), 디옥산 등) ; 지방족 탄화수소류 (펜탄, 헥산, 헵탄, 석유 에테르 등) ; 방향족 탄화수소류 (벤젠, 톨루엔, 자일렌, 메시틸렌, 클로로벤젠, 디클로로벤젠, 니트로벤젠, 테트랄린 등) ; 할로겐계 탄화수소류 (클로로포름, 디클로로메탄, 사염화탄소, 디클로로에탄 등) ; 저급 지방산 에스테르류 (아세트산메틸, 아세트산에틸, 아세트산부틸, 프로피온산메틸 등) ; 니트릴류 (아세토니트릴, 프로피오니트릴, 부티로니트릴 등) ; 등을 사용할 수 있다. 이들 용매는, 반응의 발생 용이성 등을 고려하여 적절히 선택할 수 있다. 또, 1 종 단독으로 또는 2 종 이상 혼합하여 사용할 수 있다. 필요에 따라, 적당한 탈수제나 건조제를 사용하여 용매를 건조시켜, 비수용매로서 사용할 수도 있다.For example, aprotic polar organic solvents (dimethylformamide (DMF), DMSO, DMAc, NMP, etc.); Ethers (diethyl ether (Et 2 O), diisopropyl ether (i-Pr 2 O), tertiary butyl methyl ether (TBME), cyclopentyl methyl ether (CPME), tetrahydrofuran (THF), dioxane etc) ; Aliphatic hydrocarbons (pentane, hexane, heptane, petroleum ether, etc.); Aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.); Halogen-based hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.); Lower fatty acid esters (methyl acetate, ethyl acetate, butyl acetate, methyl propionate, etc.); Nitriles (acetonitrile, propionitrile, butyronitrile, etc.); etc. can be used. These solvents can be appropriately selected in consideration of the ease with which the reaction occurs. Moreover, it can be used individually or in mixture of 2 or more types. If necessary, the solvent can be dried using an appropriate dehydrating agent or desiccant and used as a non-aqueous solvent.

용매로는, 에테르류가 바람직하고, THF 가 특히 바람직하다. THF 를 사용한 경우, 반응 종료 후에 물을 첨가하여 분액함으로써, 목적물인 식 (B) 로 나타내는 화합물은, THF 용액에 함유된 상태로 얻을 수 있다.As a solvent, ethers are preferable and THF is particularly preferable. When THF is used, the target compound represented by formula (B) can be obtained in a state contained in the THF solution by adding water and separating the layers after completion of the reaction.

THF 와 물은, 통상적으로는, 서로 혼합되어 균일한 용액이 되지만, 본 발명의 제조 방법에 있어서는, 축합 공정에서 부생한 불화칼륨이, 수상으로 용해됨으로써 수상의 염 농도가 높은 것, 목적물인 식 (B) 로 나타내는 화합물이 물에 난용성인 것 등으로부터, 양자는 양호하게 분액된다. 그 때의 THF 와 물의 비율로는, THF 1 질량부에 대해, 물 0.1 ∼ 0.5 질량부가 바람직하고, 0.3 ∼ 0.4 질량부가 보다 바람직하다.THF and water are usually mixed together to form a homogeneous solution, but in the production method of the present invention, the potassium fluoride by-produced in the condensation process is dissolved in the aqueous phase, so that the salt concentration of the aqueous phase is high, and the target product is Eq. Since the compound represented by (B) is poorly soluble in water, both are separated well. The ratio of THF to water at that time is preferably 0.1 to 0.5 parts by mass of water, and more preferably 0.3 to 0.4 parts by mass per 1 part by mass of THF.

용매의 사용량은 특별히 한정되지 않지만, 식 (C) 의 디니트로 화합물 1 질량부에 대해, 0.1 ∼ 100 질량배의 용매를 사용하는 것이 바람직하다. 보다 바람직하게는, 0.5 ∼ 30 질량배이고, 더욱 바람직하게는 1 ∼ 10 질량배이다.The amount of solvent used is not particularly limited, but it is preferable to use 0.1 to 100 times by mass of the solvent relative to 1 part by mass of the dinitro compound of formula (C). More preferably, it is 0.5 to 30 times by mass, and even more preferably, it is 1 to 10 times by mass.

반응 온도는 특별히 한정되지 않지만, -100 ℃ 로부터 사용하는 용매의 비점까지의 범위, 바람직하게는, -50 ∼ 150 ℃ 의 범위이다.The reaction temperature is not particularly limited, but is in the range from -100°C to the boiling point of the solvent used, and is preferably in the range of -50 to 150°C.

반응 시간은, 통상 0.05 ∼ 200 시간, 바람직하게는 0.5 ∼ 100 시간이다.The reaction time is usually 0.05 to 200 hours, preferably 0.5 to 100 hours.

반응 종료 후에는, 상기와 같이, 물을 첨가하여 분액함으로써, 식 (B) 로 나타내는 화합물을 함유하는 THF 용액이 얻어진다.After completion of the reaction, water is added and the liquid is separated as described above to obtain a THF solution containing the compound represented by formula (B).

이어서, 본 발명에서는, 상기에서 얻어진 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 을 환원함으로써, 4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘 (A) 이 얻어진다.Next, in the present invention, 4-(N-p-nitrophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B) obtained above is reduced to produce 4-( N-p-aminophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine (A) is obtained.

본 발명에서는, 식 (B) 의 니트로 화합물을 단리하지 않고, 이것을 함유하는 용액을 그대로, 다음 공정의 환원 반응에 제공할 수 있고, 이 경우, 반응 효율의 향상이나 수율의 향상 등의 점에서 바람직하다.In the present invention, the nitro compound of formula (B) is not isolated, but a solution containing it can be directly used for the reduction reaction in the next step, and in this case, it is preferable from the viewpoint of improving reaction efficiency and improving yield. do.

[화학식 7][Formula 7]

Figure 112017095275022-pct00007
Figure 112017095275022-pct00007

환원의 방법으로는, 촉매의 존재 하에 있어서의 수소 첨가 반응, 프로톤의 공존 하에 실시하는 환원 반응, 포름산을 수소원으로 하는 환원, 히드라진을 수소원으로 하는 환원 반응 등을 들 수 있고, 이들 환원 반응을 복수 조합해도 된다. 식 (B) 의 디니트로 화합물의 구조와 반응성을 고려하면, 환원의 방법으로는, 촉매의 존재 하에 있어서의 수소 첨가 반응이 바람직하다.Methods of reduction include a hydrogenation reaction in the presence of a catalyst, a reduction reaction carried out in the presence of protons, a reduction using formic acid as a hydrogen source, and a reduction reaction using hydrazine as a hydrogen source. These reduction reactions include: Multiple combinations may be used. Considering the structure and reactivity of the dinitro compound of formula (B), hydrogenation reaction in the presence of a catalyst is preferable as a reduction method.

수소 첨가 반응에 사용되는 촉매는, 시판품으로서 입수할 수 있는 활성탄 담지 금속이 바람직하고, 예를 들어, 팔라듐-활성탄, 백금-활성탄, 로듐-활성탄 등을 들 수 있다. 또, 수산화팔라듐, 산화 백금, 라니 니켈 등, 반드시 활성탄 담지형의 금속 촉매가 아니어도 된다. 일반적으로 널리 사용되고 있는 팔라듐-활성탄이, 반응 후에 폐기물이 발생하지 않고, 부반응이 잘 일어나지 않거나 하는 양호한 결과가 얻어지므로 바람직하다.The catalyst used in the hydrogenation reaction is preferably a commercially available activated carbon supported metal, and examples include palladium-activated carbon, platinum-activated carbon, and rhodium-activated carbon. Additionally, it does not necessarily have to be a metal catalyst supported on activated carbon, such as palladium hydroxide, platinum oxide, or Raney nickel. Palladium-activated carbon, which is generally widely used, is preferred because it produces good results in that no waste is generated after the reaction and side reactions do not occur easily.

촉매의 사용량은 특별히 한정되지 않지만, 반응성의 점에서, 상기 식 (B) 로 나타내는 화합물 1 몰에 대해, 바람직하게는 0.0001 ∼ 0.1 몰, 보다 바람직하게는 0.001 ∼ 0.01 몰이다.The amount of the catalyst used is not particularly limited, but is preferably 0.0001 to 0.1 mol, more preferably 0.001 to 0.01 mol, based on 1 mol of the compound represented by the formula (B) from the viewpoint of reactivity.

수소 첨가 반응을 보다 효과적으로 진행시키기 위해, 추가로, 활성탄의 공존 하에서 반응을 실시하는 경우도 있다. 이 때, 사용하는 활성탄의 양은 특별히 한정되지 않지만, 식 (B) 의 디니트로 화합물의 100 질량％ 에 대해, 1 ∼ 20 질량％ 가 바람직하고, 5 ∼ 10 질량％ 가 보다 바람직하다.In order to advance the hydrogenation reaction more effectively, the reaction may be further carried out in the presence of activated carbon. At this time, the amount of activated carbon to be used is not particularly limited, but is preferably 1 to 20 mass%, and more preferably 5 to 10 mass%, relative to 100 mass% of the dinitro compound of formula (B).

추가적인 반응 촉진을 위해서, 가압 수소 하에서 반응을 실시하는 경우도 있다. 이 경우, 벤젠 핵의 환원을 피하기 위해, 20 기압까지의 가압 범위에서 실시한다. 바람직하게는 10 기압까지의 범위에서 반응을 실시한다.To further promote the reaction, the reaction may be carried out under pressurized hydrogen. In this case, in order to avoid reduction of benzene nuclei, it is carried out in a pressurized range of up to 20 atm. Preferably, the reaction is carried out in a pressure range of up to 10 atmospheres.

용매는, 각 원료와 반응하지 않는 용매이면, 제한없이 사용할 수 있다.The solvent can be used without limitation as long as it is a solvent that does not react with each raw material.

예를 들어, 비프로톤성 극성 유기 용매 (DMF, DMSO, DMAc, NMP 등) ; 에테르류 (Et2O, i-Pr2O, TBME, CPME, THF, 디옥산 등) ; 지방족 탄화수소류 (펜탄, 헥산, 헵탄, 석유 에테르 등) ; 방향족 탄화수소류 (벤젠, 톨루엔, 자일렌, 메시틸렌, 클로로벤젠, 디클로로벤젠, 니트로벤젠, 테트랄린 등) ; 할로겐계 탄화수소류 (클로로포름, 디클로로메탄, 사염화탄소, 디클로로에탄 등) ; 저급 지방산 에스테르류(아세트산메틸, 아세트산에틸, 아세트산부틸, 프로피온산메틸 등) ; 니트릴류 (아세토니트릴, 프로피오니트릴, 부티로니트릴 등) ; 등을 사용할 수 있다. 그 중에서도, THF, 디옥산, 아세트산에틸이 바람직하다.For example, aprotic polar organic solvents (DMF, DMSO, DMAc, NMP, etc.); Ethers (Et 2 O, i-Pr 2 O, TBME, CPME, THF, dioxane, etc.); Aliphatic hydrocarbons (pentane, hexane, heptane, petroleum ether, etc.); Aromatic hydrocarbons (benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene, nitrobenzene, tetralin, etc.); Halogen-based hydrocarbons (chloroform, dichloromethane, carbon tetrachloride, dichloroethane, etc.); Lower fatty acid esters (methyl acetate, ethyl acetate, butyl acetate, methyl propionate, etc.); Nitriles (acetonitrile, propionitrile, butyronitrile, etc.); etc. can be used. Among them, THF, dioxane, and ethyl acetate are preferable.

이들 용매는, 반응의 발생 용이성 등을 고려하여 적절히 선택할 수 있다. 또, 1 종 단독으로 또는 2 종 이상 혼합하여 사용할 수 있다. 필요에 따라, 적당한 탈수제나 건조제를 사용하여 용매를 건조시켜, 비수용매로서 사용할 수도 있다.These solvents can be appropriately selected in consideration of the ease with which the reaction occurs. Moreover, it can be used individually or in mixture of 2 or more types. If necessary, the solvent can be dried using an appropriate dehydrating agent or desiccant and used as a non-aqueous solvent.

용매의 사용량 (반응 농도) 은 특별히 한정되지 않지만, 식 (B) 의 디니트로 화합물의 1 질량부에 대해, 0.1 ∼ 100 질량배이다. 바람직하게는 0.5 ∼ 30 질량배이고, 더욱 바람직하게는 1 ∼ 10 질량배이다.The amount of solvent used (reaction concentration) is not particularly limited, but is 0.1 to 100 times by mass relative to 1 part by mass of the dinitro compound of formula (B). Preferably it is 0.5 to 30 times by mass, and more preferably 1 to 10 times by mass.

반응 온도는 특별히 한정되지 않지만, -100 ℃ 로부터 사용하는 용매의 비점까지의 범위, 바람직하게는, -50 ∼ 150 ℃ 이다. 반응 시간은, 통상 0.05 ∼ 350 시간, 바람직하게는 0.5 ∼ 100 시간이다.The reaction temperature is not particularly limited, but ranges from -100°C to the boiling point of the solvent used, and is preferably -50 to 150°C. The reaction time is usually 0.05 to 350 hours, preferably 0.5 to 100 hours.

실시예Example

이하, 본 발명을 실시예에 의해 더욱 구체적으로 설명하지만, 이들 실시예에 의해 본 발명의 해석이 한정되는 것은 아니다. 또한, 실시예에 있어서 채용한 분석 장치 및 분석 조건은 하기와 같다.Hereinafter, the present invention will be described in more detail by way of examples, but the interpretation of the present invention is not limited to these examples. In addition, the analysis equipment and analysis conditions employed in the examples are as follows.

(1H-NMR 의 측정)( 1H -NMR measurement)

장치 : Varian NMR system 400NB (400 ㎒) (Varian 사 제조), 및 JMTC-500/54/SS (500 ㎒) (JEOL 사 제조)Device: Varian NMR system 400NB (400 MHz) (manufactured by Varian), and JMTC-500/54/SS (500 MHz) (manufactured by JEOL)

측정 용매 : CDCl3 (중수소화 클로로포름), DMSO-d6 (중수소화 디메틸술폭사이드)Measurement solvent: CDCl 3 (deuterated chloroform), DMSO-d 6 (deuterated dimethyl sulfoxide)

기준 물질 : TMS (테트라메틸실란) (δ : 0.0 ppm, 1H) 및 CDCl3 (δ : 77.0 ppm, 13C)Reference substances: TMS (tetramethylsilane) (δ: 0.0 ppm, 1 H) and CDCl 3 (δ: 77.0 ppm, 13 C)

(HPLC (고속 액체 크로마토그래피) 의 측정)(Measurement by HPLC (high performance liquid chromatography))

장치 : LC-20AD (시마즈 제작소사 제조)Device: LC-20AD (manufactured by Shimadzu Corporation)

칼럼 : X Bridge BEHC18 5 ㎛, 4.6 × 250 ㎜ Column (Waters)Column: X Bridge BEHC18 5 ㎛, 4.6 × 250 ㎜ Column (Waters)

검출기 : SPD-M20A (시마즈 제작소사 제조) (검출 파장 : 254 ㎚)Detector: SPD-M20A (manufactured by Shimadzu Corporation) (detection wavelength: 254 nm)

용리액 : MeOH/0.2 ％ AcOH, 0.8 ％ Et3N aq. = 70/30 [vol/vol]Eluent: MeOH/0.2% AcOH, 0.8% Et3N aq. = 70/30 [vol/vol]

＜4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘의 합성＞<Synthesis of 4-(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine>

[화학식 8][Formula 8]

Figure 112017095275022-pct00008
Figure 112017095275022-pct00008

＜축합 공정＞＜Condensation process＞

1 ℓ (리터) 의 4 구 플라스크에, 4-(아미노메틸)피페리딘 (15.0 g, 131.4 ㎜ol), 탄산칼륨 (21.8 g, 157.7 ㎜ol) 및 N-메틸피롤리돈 (40.5 g) 을 주입하고, 날개 교반 하에 75 ℃ 로까지 승온하였다. 그 후, p-플루오로니트로벤젠 (38.9 g, 275.9 ㎜ol), 및 N-메틸피롤리돈 (7.5 g) 을 2 시간에 걸쳐 적하하고, 75 ℃ 에서 6 시간 교반하였다. HPLC 에 의해 반응 종료를 확인한 후, 반응액을 그대로 사용하여, 다음 공정으로 진행하였다.In a 1 liter (liter) four-necked flask, 4-(aminomethyl)piperidine (15.0 g, 131.4 mmol), potassium carbonate (21.8 g, 157.7 mmol) and N-methylpyrrolidone (40.5 g) was injected, and the temperature was raised to 75° C. under wing stirring. After that, p-fluoronitrobenzene (38.9 g, 275.9 mmol) and N-methylpyrrolidone (7.5 g) were added dropwise over 2 hours, and the mixture was stirred at 75°C for 6 hours. After confirming the completion of the reaction by HPLC, the reaction solution was used as is and proceeded to the next step.

＜Boc 공정＞＜Boc process＞

전공정의 반응액에 테트라하이드로푸란 (270.0 g), 및 DMAP (N,N-dimethyl-4-aminopyridine) (0.80 g, 6.57 ㎜ol) 를 주입하고, Boc2O (이탄산디-tert-부틸) (57.3 g, 262.5 ㎜ol) 를 30 분에 걸쳐 적하한 후, 1 시간 교반하였다. HPLC 에 의해 반응 종료를 확인하고, 그 후, 테트라하이드로푸란 (15.0 g), 및 물 (90.0 g) 을 첨가하여 교반하였다 (1 시간). 이어서, 분액하여 수층을 제거하고, THF 용액을 그대로 사용하여, 다음 공정으로 진행하였다.Tetrahydrofuran (270.0 g) and DMAP (N,N-dimethyl-4-aminopyridine) (0.80 g, 6.57 mmol) were added to the reaction solution of the previous step, and Boc 2 O (di-tert-butyl bicarbonate) ( 57.3 g, 262.5 mmol) was added dropwise over 30 minutes, and then stirred for 1 hour. Completion of the reaction was confirmed by HPLC, and then tetrahydrofuran (15.0 g) and water (90.0 g) were added and stirred (1 hour). Next, the water layer was removed by liquid separation, and the THF solution was used as is to proceed to the next step.

＜환원 공정＞＜Reduction process＞

상기 THF 용액에 5 질량％ Pd/C (50 질량％ 함수형) (3.0 g), 및 활성탄 (시라사기 WP-H (6.0 g)) 을 주입하였다. 그 후, 수소 치환을 실시하고, 50 ℃ 로 승온한 후, 5 시간 교반하였다. HPLC 에 의해 반응 종료를 확인한 후, 멤브레인 필터에 의해 여과를 실시하여, Pd/C 등을 제거하였다. 그 후, 내용량이 210.0 g 이 될 때까지 농축시켰다. 이어서, 2-프로판올 (420.0 g) 을 적하하고, 5 ℃ 로 냉각시키고, 다시 1 시간 교반하였다. 석출된 결정을 감압 여과하고, 2-프로판올 (27.0 g) 로 세정한 후, 건조시켜, 분말 결정으로서, 4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘을 얻었다 (수량 44.3 g, 수율 85.0 ％).5 mass% Pd/C (50 mass% hydrous) (3.0 g) and activated carbon (Shirasagi WP-H (6.0 g)) were injected into the THF solution. After that, hydrogen substitution was performed, the temperature was raised to 50°C, and then the mixture was stirred for 5 hours. After confirming the completion of the reaction by HPLC, filtration was performed using a membrane filter to remove Pd/C, etc. After that, it was concentrated until the net weight was 210.0 g. Next, 2-propanol (420.0 g) was added dropwise, cooled to 5°C, and stirred for another 1 hour. The precipitated crystals were filtered under reduced pressure, washed with 2-propanol (27.0 g), dried, and 4-(N-p-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-( p-aminophenyl)piperidine was obtained (quantity 44.3 g, yield 85.0%).

Figure 112017095275022-pct00009
Figure 112017095275022-pct00009

본 발명에서 얻어지는 4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘은, 액정 배향막 등에 사용되는 폴리이미드 전구체 혹은 폴리이미드의 원료 재료로서 유용하다.4-(N-p-aminophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine obtained in the present invention is a polyimide precursor or a raw material for polyimide used in liquid crystal alignment films, etc. Useful as a material.

또한, 2015년 3월 9일에 출원된 일본 특허출원 2015-045862호의 명세서, 특허 청구의 범위, 및 요약서의 전체 내용을 여기에 인용하고, 본 발명의 명세서의 개시로서 받아들이는 것이다.In addition, the entire contents of the specification, claims, and abstract of Japanese Patent Application No. 2015-045862 filed on March 9, 2015 are hereby cited and accepted as disclosure of the specification of the present invention.

Claims (11)

p-플루오로니트로벤젠과 4-(아미노메틸)피페리딘을, N-메틸피롤리돈의 용매 중에서 반응시키는, 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 의 제조 방법.
[화학식 1]
Figure 112023035392438-pct00010
4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)pi, which is reacted with p-fluoronitrobenzene and 4-(aminomethyl)piperidine in a solvent of N-methylpyrrolidone. Method for producing peridine (C).
[Formula 1]
Figure 112023035392438-pct00010
 제 1 항에 있어서,
탄산 칼륨의 존재 하에 반응시키는 제조 방법.According to claim 1,
A manufacturing method involving reaction in the presence of potassium carbonate. 제 1 항에 있어서,
4-(아미노메틸)피페리딘 1 몰에 대해, p-플루오로니트로벤젠을 2 ∼ 10 몰 반응시키는 제조 방법.According to claim 1,
A production method in which 2 to 10 moles of p-fluoronitrobenzene are reacted with respect to 1 mole of 4-(aminomethyl)piperidine. 삭제delete 제 1 항에서 얻어지는 4-(p-니트로페닐아미노메틸)-N-(p-니트로페닐)피페리딘 (C) 을 터셔리부틸옥시카르보닐화하는, 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 의 제조 방법.
[화학식 2]
Figure 112023035392438-pct00011
4-(Np-nitrophenyl-N-, which is tert-butyloxycarbonylated 4-(p-nitrophenylaminomethyl)-N-(p-nitrophenyl)piperidine (C) obtained in claim 1. Method for producing tertiarybutoxycarbonylamino)methyl-N-(p-nitrophenyl)piperidine (B).
[Formula 2]
Figure 112023035392438-pct00011
 제 5 항에 있어서,
상기 터셔리부틸옥시카르보닐화를 염기의 존재 하에서 실시하는 제조 방법.According to claim 5,
A production method in which the tertiary butyloxycarbonylation is carried out in the presence of a base. 제 5 항에 있어서,
상기 터셔리부틸옥시카르보닐화제의 사용량이 식 (C) 로 나타내는 화합물 1 몰에 대해 1 ∼ 5 몰인 제조 방법.According to claim 5,
A production method wherein the amount of the tertiary-butyloxycarbonylating agent used is 1 to 5 moles per mole of the compound represented by formula (C). 제 5 항에 있어서,
상기 터셔리부틸옥시카르보닐화를 테트라하이드로푸란의 용매 중에서 실시하는 제조 방법.According to claim 5,
A production method in which the tertiary butyloxycarbonylation is carried out in a solvent of tetrahydrofuran. 제 5 항 내지 제 8 항 중 어느 한 항에서 얻어지는 터셔리부틸옥시카르보닐화된 4-(N-p-니트로페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-니트로페닐)피페리딘 (B) 을 환원하는, 4-(N-p-아미노페닐-N-터셔리부톡시카르보닐아미노)메틸-N-(p-아미노페닐)피페리딘 (A) 의 제조 방법.
[화학식 3]
Figure 112017095275022-pct00012
Terti-butyloxycarbonylated 4-(Np-nitrophenyl-N-tertibutoxycarbonylamino)methyl-N-(p-nitrophenyl)py obtained according to any one of claims 5 to 8 A method for producing 4-(Np-aminophenyl-N-tertiarybutoxycarbonylamino)methyl-N-(p-aminophenyl)piperidine (A), which reduces peridine (B).
[Formula 3]
Figure 112017095275022-pct00012
 제 9 항에 있어서,
촉매의 존재 하에 있어서의 수소 첨가 반응에 의해 환원하는 제조 방법.According to clause 9,
A production method that involves reduction by hydrogenation reaction in the presence of a catalyst. 제 9 항에 있어서,
활성탄 담지 촉매의 존재 하에 환원하는 제조 방법.According to clause 9,
A production method of reduction in the presence of an activated carbon-supported catalyst.
KR1020177027754A 2015-03-09 2016-03-07 Diamine compound and method for producing intermediate thereof KR102592383B1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2015045862 2015-03-09
JPJP-P-2015-045862 2015-03-09
PCT/JP2016/057022 WO2016143748A1 (en) 2015-03-09 2016-03-07 Diamine compound and method for producing intermediate thereof

Publications (2)

Publication Number Publication Date
KR20170127495A KR20170127495A (en) 2017-11-21
KR102592383B1 true KR102592383B1 (en) 2023-10-20

Family

ID=56880204

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1020177027754A KR102592383B1 (en) 2015-03-09 2016-03-07 Diamine compound and method for producing intermediate thereof

Country Status (5)

Country Link
JP (1) JP6669159B2 (en)
KR (1) KR102592383B1 (en)
CN (1) CN107406385B (en)
TW (1) TWI691485B (en)
WO (1) WO2016143748A1 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117089070B (en) * 2023-08-21 2024-04-16 波米科技有限公司 Liquid crystal aligning agent and application thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3191535B2 (en) 1993-10-21 2001-07-23 ジェイエスアール株式会社 Liquid crystal alignment agent and liquid crystal display device
JP3206401B2 (en) 1995-11-20 2001-09-10 ジェイエスアール株式会社 Liquid crystal alignment agent and liquid crystal display device
JP3650982B2 (en) * 1996-10-02 2005-05-25 Ｊｓｒ株式会社 Liquid crystal aligning agent and liquid crystal display element
JP2012155311A (en) * 2011-01-05 2012-08-16 Jnc Corp Liquid crystal aligning agent for forming photo-aligning liquid crystal alignment layer, liquid crystal alignment layer and liquid crystal display element using the same
JP5874590B2 (en) * 2011-12-26 2016-03-02 Jsr株式会社 Liquid crystal aligning agent, liquid crystal aligning film, liquid crystal display element, polymer and compound
WO2015122413A1 (en) * 2014-02-13 2015-08-20 日産化学工業株式会社 Novel liquid crystal orientation agent, diamine, and polyimide precursor
JP6555257B2 (en) * 2014-05-30 2019-08-07 日産化学株式会社 Liquid crystal aligning agent, liquid crystal aligning film, and liquid crystal display element
KR102486076B1 (en) * 2014-10-03 2023-01-06 닛산 가가쿠 가부시키가이샤 Liquid crystal aligning agent, liquid crystal alignment film and liquid crystal display element using same

Also Published As

Publication number Publication date
CN107406385A (en) 2017-11-28
WO2016143748A1 (en) 2016-09-15
JP6669159B2 (en) 2020-03-18
CN107406385B (en) 2021-01-26
JPWO2016143748A1 (en) 2017-12-21
KR20170127495A (en) 2017-11-21
TWI691485B (en) 2020-04-21
TW201708192A (en) 2017-03-01

Similar Documents

Publication Publication Date Title
EP3782980A1 (en) Perfluoropolyether compound containing carboxyl group
KR101832534B1 (en) Method for preparing diamine precursor compound
KR102592383B1 (en) Diamine compound and method for producing intermediate thereof
JP5689321B2 (en) Process for producing 2-amino-4-trifluoromethylpyridines
WO2009128512A1 (en) Method for producing pyrimidine compound
US8748664B2 (en) Diamine compound and production method thereof
JP2014181185A (en) Method for manufacturing diamine compound
KR102544307B1 (en) Manufacturing method of aromatic diamine compound precursor
JP6247992B2 (en) Method for producing halogen compound
JP3031036B2 (en) Fluorinated aromatic diamine compound, fluorinated diamine compound in which amino group is protected, and methods for producing them
JP5790645B2 (en) Novel process for producing bisaminophenylalkylurea
JP3018643B2 (en) Process for producing fluorine-containing diaminobenzene compound and fluorine-containing aromatic diamine compound
WO2018116836A1 (en) Method for producing polymerizable compound
JPH05229994A (en) Fluorine-containing aromatic diamine compond, fluorine-containing bis(aminobenzene) compound, bis(aminophenol) compound and their production
JP5279449B2 (en) Process for producing 5- {4- [2- (5-ethyl-2-pyridyl) ethoxy] benzyl} -2,4-thiazolidinedione hydrochloride
KR20190032253A (en) Method of preparing diamine compound
JP5851974B2 (en) Diamine compound and method for producing the same
JP2004331520A (en) Method for producing 2,5-bis(isocyanatomethyl)-1,4-dithianes and intermediate therefor
JP2018035185A (en) Method for producing potassium salt, and potassium salt
JP2784445B2 (en) New diisocyanate and method for producing the same
JP2001172239A (en) Fluorine-containing aromatic diamine compound, fluorine- containing bis(aminobenzene) compound, bis(aminopbenol) compound and method for producing the same
JPWO2008007763A1 (en) Method for producing imidazolidine-2,4-dione compound and method for obtaining solid 4,5-dihydroxy-2-imidazolidinone compound
JPS62123162A (en) Production of cyano-substituted aniline compound
JPH06100508A (en) Aromatic amine compound and aromatic unsaturated imide compound
DE19962932A1 (en) Production of N-substituted 2,4-diamino-5-fluoro-benzonitrile derivatives, useful as herbicide intermediates, involves multi-stage process from 2-bromo-4-fluoro-aniline via known and new intermediates

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
E701 Decision to grant or registration of patent right
GRNT Written decision to grant