JP2010229079A - Method for producing primary allylamine compound - Google Patents

Method for producing primary allylamine compound Download PDF

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JP2010229079A
JP2010229079A JP2009078342A JP2009078342A JP2010229079A JP 2010229079 A JP2010229079 A JP 2010229079A JP 2009078342 A JP2009078342 A JP 2009078342A JP 2009078342 A JP2009078342 A JP 2009078342A JP 2010229079 A JP2010229079 A JP 2010229079A
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JP5557460B2 (en
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Osamu Kobayashi
修 小林
Takashi Nagano
高志 永野
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing unprotected primary allylamine compound directly from ammonia without requiring any ammonia equivalent. <P>SOLUTION: The primary allylamine compound is produced by reacting an allyl acetate or allyl carbonate represented by formula (1) (wherein R is alkyl group, alkylene group or aryl group; R<SP>1</SP>is hydrogen atom, alkyl group or aryl group; and X is OAc or OCO<SB>2</SB>CH<SB>3</SB>) and ammonia (NH<SB>3</SB>) in a liquid phase in the presence of a palladium catalyst. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

この発明は、パラジウム触媒を用いて第１級アリルアミン化合物を製造する方法に関する。   The present invention relates to a method for producing a primary allylamine compound using a palladium catalyst.

従来、パラジウム触媒を用いるアリル位アミノ化反応では、アンモニアを用いることはできないとされている（非特許文献１）。そのため、種々のアンモニア等価体を用いて反応を行い、一級アミンを得るためにさらに生成物を脱保護する必要があった。例えば、これまでに、4,4-ジメトキシベンズヒドリルアミン（非特許文献２）、トルエンスルホンアミド（非特許文献３）、フタルイミド（非特許文献４）、ジ-t-ブチルイミノジカーボネート（非特許文献５）、アジド（非特許文献６）などをアンモニア等価体とする反応が報告されている。   Conventionally, ammonia cannot be used in an allylic amination reaction using a palladium catalyst (Non-patent Document 1). Therefore, it was necessary to carry out the reaction using various ammonia equivalents and to further deprotect the product in order to obtain a primary amine. For example, to date, 4,4-dimethoxybenzhydrylamine (Non-Patent Document 2), toluenesulfonamide (Non-Patent Document 3), phthalimide (Non-Patent Document 4), di-t-butyliminodicarbonate (Non-Patent Document 2) Literature 5), azide (Non-patent Literature 6) and the like have been reported as reactions with ammonia equivalents.

Johannsen, M.; Jorgensen, K. A. Chem. Rev. 1998, 98, 1689.Johannsen, M .; Jorgensen, K. A. Chem. Rev. 1998, 98, 1689. Trost, B. M.; Keinan, E. J. Org. Chem. 1979, 44, 3451.Trost, B. M .; Keinan, E. J. Org. Chem. 1979, 44, 3451. Bystrom, S. E.; Aslanian, R.; Backvall, J.-E. Tetrahedron Lett. 1985, 26, 1749.Bystrom, S. E .; Aslanian, R .; Backvall, J.-E.Tetrahedron Lett. 1985, 26, 1749. Inoue, Y.; Taguchi, M.; Toyofuku, M.; Hashimoto, H. Bull. Chem. Soc. Jpn. 1984, 57, 3021.Inoue, Y .; Taguchi, M .; Toyofuku, M .; Hashimoto, H. Bull. Chem. Soc. Jpn. 1984, 57, 3021. Connell, R. D.; Rein, T.; Akermark, B.; Helquist, P. J. Org. Chem. 1988, 53, 3845.Connell, R. D .; Rein, T .; Akermark, B .; Helquist, P. J. Org. Chem. 1988, 53, 3845. Murahashi, S.-I.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y. J. Org. Chem. 1989, 54, 3292.Murahashi, S.-I .; Taniguchi, Y .; Imada, Y .; Tanigawa, Y. J. Org. Chem. 1989, 54, 3292.

しかし、アンモニア等価体を用いる反応は溶媒等が高価であるという問題がある。
このようなことから、本発明は、アンモニア等価体を不要とし、アンモニアから直接、保護されていない第１級アリルアミン化合物を製造する方法の提供を目的とする。 However, the reaction using an ammonia equivalent has a problem that the solvent is expensive.
Therefore, an object of the present invention is to provide a method for producing a primary allylamine compound that does not require an ammonia equivalent and is not directly protected from ammonia.

即ち、本発明の方法は、パラジウム触媒の存在下、液相で下式（化１）

Figure 2010229079
（式中、Ｒはアルキル基、アルキレン基、又はアリール基を表し、Ｒ１は水素原子、アルキル基又はアリール基を表し、ＸはＯＣＯＲ２又はＯＣＯ２Ｒ２を表す。但し、Ｒ２は炭素数１〜１０のアルキル基、アラルキル基、又はアリール基）で表されるアリルアセテートまたはアリルカーボネートと、アンモニア（ＮＨ３）とを反応させて第１級アリルアミン化合物を製造するものである。 That is, the process of the present invention is carried out in the liquid phase in the presence of a palladium catalyst.
Figure 2010229079
 (In the formula, R represents an alkyl group, an alkylene group, or an aryl group, R 1 represents a hydrogen atom, an alkyl group, or an aryl group, and X represents OCOR 2 or OCO 2 R 2 , where R 2 represents carbon. A primary allylamine compound is produced by reacting allyl acetate or allyl carbonate represented by an alkyl group, aralkyl group, or aryl group of formulas 1 to 10 with ammonia (NH 3 ).

前記アンモニア（ＮＨ３）としてアンモニア水を使用し、ジオキサン中で反応させることが好ましい。 It is preferable to use ammonia water as the ammonia (NH 3 ) and react in dioxane.

本発明によれば、アンモニア等価体を不要とし、アンモニアから直接、保護されていない第１級アリルアミン化合物を製造することができる。   According to the present invention, a primary allylamine compound which does not require an ammonia equivalent and is not directly protected from ammonia can be produced.

本発明は、パラジウム触媒の存在下、液相で下式（化１）

Figure 2010229079
（式中、Ｒはアルキル基、アルキレン基、又はアリール基を表し、Ｒ１は水素原子、アルキル基又はアリール基を表し、ＸはＯＣＯＲ２又はＯＣＯ２Ｒ２を表す。但し、Ｒ２は炭素数１〜１０のアルキル基、アラルキル基、又はアリール基）で表されるアリルアセテートまたはアリルカーボネートと、アンモニア（ＮＨ３）とを反応させ、第１級アリルアミン化合物を製造する方法である。
Ｒとしては、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｔ−ブチル基、アルキレン基、フェニル基、p-OMeC6H4, m-NO2C6H4, 3,5-(CF3) 2C6H3-, 1-ナフチル基, 2-ナフチル基, -(CH2) 2Ph, -CH2N(Ts)CH2-、を例示することができ、特にアルキレン基,又はフェニル基が好ましい。
Ｒ１としては、水素原子、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｔ−ブチル基、フェニル基、p-OMeC6H4, m-NO2C6H4, 3,5-(CF3) 2C6H3-,1-ナフチル基, 2-ナフチル基, -(CH2) 3Ph、を例示することができ、特に、フェニル基、p-OMeC6H4, m-NO2C6H4, 又は3,5-(CF3) 2C6H3-が好ましい。
ＲとＲ１の組み合わせとしては、Ｒがアルキレン基,又はフェニル基で、Ｒ１が水素原子又はフェニル基であるものを例示することができる。 The present invention provides the following formula in the liquid phase in the presence of a palladium catalyst:
Figure 2010229079
 (In the formula, R represents an alkyl group, an alkylene group, or an aryl group, R 1 represents a hydrogen atom, an alkyl group, or an aryl group, and X represents OCOR 2 or OCO 2 R 2 , where R 2 represents carbon. This is a method for producing a primary allylamine compound by reacting allyl acetate or allyl carbonate represented by an alkyl group, aralkyl group or aryl group of formulas 1 to 10 with ammonia (NH 3 ).
R includes methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, alkylene, phenyl, p-OMeC 6 H 4 , m-NO 2 C 6 H 4 , 3,5- (CF 3 ) 2 C 6 H 3- , 1-naphthyl group, 2-naphthyl group,-(CH 2 ) 2 Ph, -CH 2 N (Ts) CH 2- In particular, an alkylene group or a phenyl group is preferable.
R 1 is hydrogen atom, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, t-butyl group, phenyl group, p-OMeC 6 H 4 , m-NO 2 C 6 H 4 , 3,5- (CF 3 ) 2 C 6 H 3- , 1-naphthyl group, 2-naphthyl group,-(CH 2 ) 3 Ph, in particular, phenyl group, p-OMeC 6 H 4 , m-NO 2 C 6 H 4 , or 3,5- (CF 3 ) 2 C 6 H 3 -is preferred.
Examples of the combination of R and R 1 include those in which R is an alkylene group or a phenyl group, and R 1 is a hydrogen atom or a phenyl group.

Ｒ２は炭素数１〜１０のアルキル基、アラルキル基、又はアリール基であり、好ましくは、メチル基、エチル基、イソプロピル基、又はフェニル基である。 R 2 is an alkyl group having 1 to 10 carbon atoms, an aralkyl group, or an aryl group, preferably a methyl group, an ethyl group, an isopropyl group, or a phenyl group.

パラジウム触媒としては、例えば化学反応に用いる種々のものを使用することができ、パラジウム錯体、酸化パラジウム、塩化パラジウム、テトラアンミンパラジウム等が挙げられる。パラジウム触媒は、反応系内でその一部でも溶解するものであれば使用できる。触媒の形態も、例えば粉末、粒状等とすることができる。
特に、有機化合物を配位子としてもつパラジウム錯体が好ましく、例えば脂環式炭化水素であるジエン類（例えばシクロオクタジエン(cod)、ホスフィン化合物（例えばトリフェニルホスフィン、トリ（ｏ−トリルホスフィン））が配位したものが例示できる。具体的に、Pd(PPh3)4、[PdCl(allyl)]2が挙げられる。 As a palladium catalyst, the various thing used for a chemical reaction can be used, for example, A palladium complex, palladium oxide, palladium chloride, tetraammine palladium, etc. are mentioned. The palladium catalyst can be used as long as even a part of the palladium catalyst is dissolved in the reaction system. The form of the catalyst can also be, for example, powder, granular form, and the like.
In particular, a palladium complex having an organic compound as a ligand is preferable. For example, dienes which are alicyclic hydrocarbons (for example, cyclooctadiene (cod), phosphine compounds (for example, triphenylphosphine, tri (o-tolylphosphine)) Examples thereof include Pd (PPh 3 ) 4 and [PdCl (allyl)] 2 .

本発明の方法では、溶媒は特に制限はないが、アンモニア等価体が不要でアンモニアから直接、保護されていない第１級アリルアミン化合物を製造できるため、高価な溶媒を必要とせず、水または低級アルコールおよび水と混和するＴＨＦ（テトラヒドロフラン）やジオキサンなどを好適に用いることができる。   In the method of the present invention, the solvent is not particularly limited, but an ammonia equivalent is not required, and an unprotected primary allylamine compound can be produced directly from ammonia. Therefore, an expensive solvent is not required, and water or a lower alcohol is used. Further, THF (tetrahydrofuran), dioxane and the like which are miscible with water can be preferably used.

反応に用いるアンモニア（ＮＨ３）としては、アンモニア水（１〜２５％）又はアンモニアガスを溶解した溶剤などを例示することができる。アンモニアとして液体アンモニアを使用する場合には、溶媒としてアルコールを用いることが好ましく、アンモニアとしてアンモニア水を使用する場合には、溶媒として含水有機溶媒、又は有機溶媒を含まない水溶液を用いることが好ましい。
溶媒中の各成分の濃度はそれぞれ0.01〜5mol/lであることが好ましい。
この反応の温度は、好ましくは-78〜60℃である。
この反応時間は、数分〜数１０時間程度である。
この反応系には上記成分のほか、適宜、触媒や界面活性剤等の公知の添加剤を添加してもよい。 The ammonia (NH 3) used in the reaction, and the like can be exemplified solvents to dissolve the ammonia water (1% to 25%) or ammonia gas. When using liquid ammonia as ammonia, it is preferable to use alcohol as the solvent, and when using ammonia water as ammonia, it is preferable to use a water-containing organic solvent or an aqueous solution containing no organic solvent as the solvent.
The concentration of each component in the solvent is preferably 0.01 to 5 mol / l.
The temperature of this reaction is preferably -78 to 60 ° C.
This reaction time is about several minutes to several tens of hours.
In addition to the above components, known additives such as catalysts and surfactants may be added to this reaction system as appropriate.

以上の反応により、下式（化２）

Figure 2010229079
で表される第１級アリルアミン化合物が生成物として得られる。生成物は抽出、カラムクロマトグラフィー、蒸留、再結晶等の一般的精製法を利用して回収できる。 By the above reaction, the following formula (Formula 2)
Figure 2010229079
 Is obtained as a product. The product can be recovered using common purification methods such as extraction, column chromatography, distillation, recrystallization and the like.

このようにして製造した第１級アリルアミン化合物は、医薬中間体等の用途に用いることができる。   The primary allylamine compound thus produced can be used for uses such as pharmaceutical intermediates.

以下、実施例にて本発明を例証するが本発明を限定することを意図するものではない。
なお、パラジウム触媒としては、Pd(PPh3)4、または[PdCl(allyl)]2（いずれも和光純薬社製）を用いた。(R)-BINAP は東京化成社製を用いた。アンモニア水（２５％）は和光純薬社製を用いた。
1H NMR と 13C NMR は 日本電子社製のJEOL JNM-ECX-400, JNM-ECX-500または、 JNM-ECX-600を使用した。又、CDCl3 を溶媒とし、テトラメチルシラン (δ = 0、 1H NMR) またはCDCl3 (δ = 77.0、13C NMR)を内部標準物質に用いて測定した。カラムクロマトグラフィーには、シリカゲル（Silica gel 60 、メルク社製）を使用し、調整用薄層クロマトグラフィーには、Wakogel B-5Fを使用した。 The following examples illustrate the invention but are not intended to limit the invention.
As the palladium catalyst, Pd (PPh 3 ) 4 or [PdCl (allyl)] 2 (both manufactured by Wako Pure Chemical Industries, Ltd.) was used. (R) -BINAP manufactured by Tokyo Chemical Industry Co., Ltd. was used. Ammonia water (25%) manufactured by Wako Pure Chemical Industries, Ltd. was used.
For 1H NMR and 13C NMR, JEOL JNM-ECX-400, JNM-ECX-500 or JNM-ECX-600 manufactured by JEOL Ltd. was used. Further, CDCl3 was used as a solvent, and tetramethylsilane (δ = 0, 1H NMR) or CDCl3 (δ = 77.0, 13C NMR) was used as an internal standard substance. Silica gel (Silica gel 60, manufactured by Merck & Co., Inc.) was used for column chromatography, and Wakogel B-5F was used for adjustment thin layer chromatography.

＜実施例１＞
表１に示す基質（アリルアセテートまたはアリルカーボネート）（0.3 mmol）を、1,4-ジオキサン／アンモニア水混合溶媒（体積比２／１）に溶解させ、この溶液にPd(PPh3)4 (35 mg, 0.03 mmol)を加えた。アリルアセテートまたはアリルカーボネートの添加量は、表１の反応条件Ａ（0.04M）又はＢ（0.11M）の濃度になるようにした。
反応液を室温にて表１の反応条件Ａ（18時間）又はＢ（12時間）で撹拌後、飽和炭酸水素ナトリウム水溶液 (5.0 mL) を加えて希釈した。反応液をジクロロメタンで３回抽出し、有機層を無水硫酸マグネシウムで乾燥後、ろ過、減圧濃縮し、粗生成物を得た。薄層クロマトグラフィー（展開溶媒：n-ヘキサン／イソプロピルアミン＝１９／１）により精製し、目的とするアリルアミンを得た。反応式を式（３）に示し、結果を表１に示す。 <Example 1>
A substrate (allyl acetate or allyl carbonate) (0.3 mmol) shown in Table 1 was dissolved in a 1,4-dioxane / ammonia water mixed solvent (volume ratio 2/1), and Pd (PPh 3 ) 4 (35 mg, 0.03 mmol) was added. The amount of allyl acetate or allyl carbonate added was adjusted to a concentration of reaction condition A (0.04M) or B (0.11M) in Table 1.
The reaction solution was stirred at room temperature under the reaction conditions A (18 hours) or B (12 hours) shown in Table 1, and then diluted with a saturated aqueous sodium hydrogen carbonate solution (5.0 mL). The reaction solution was extracted three times with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product. Purification by thin layer chromatography (developing solvent: n-hexane / isopropylamine = 19/1) yielded the desired allylamine. The reaction formula is shown in Formula (3), and the results are shown in Table 1.

Figure 2010229079
Figure 2010229079

Figure 2010229079
Figure 2010229079

各実験例の基質の作製方法と、生成物の同定結果を以下に示す。
実験例１
基質であるアリル化合物（(E)-1,3-Diphenylallyl acetate）は、文献Ａ（Nemoto, T.; Jin, L.; Nakamura, H.; Hamada, Y. Tetrahedron Lett. 2006, 47, 6577.）に従い合成した。
生成物のアリルアミン：(E)-1,3-Diphenyl-2-propene-1-amine (2a). 1H NMR (400 MHz, CDCl3): δ 7.41-7.19 (m, 10H), 6.59 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 6.4 Hz, 1H), 4.71 (d, J = 6.4 Hz, 2H), 2.14 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ 144.0, 136.8, 133.3, 129.3, 128.6, 128.5, 127.5, 127.3, 126.7, 126.4, 57.9. The production method of the substrate of each experimental example and the identification result of the product are shown below.
Experimental example 1
The allyl compound ((E) -1,3-Diphenylallyl acetate) which is a substrate is described in Reference A (Nemoto, T .; Jin, L .; Nakamura, H .; Hamada, Y. Tetrahedron Lett. 2006, 47, 6577. ) And synthesized.
Product Allylamine: (E) -1,3-Diphenyl-2-propene-1-amine (2a). 1 H NMR (400 MHz, CDCl 3 ): δ 7.41-7.19 (m, 10H), 6.59 (d , J = 16.0 Hz, 1H), 6.37 (dd, J = 16.0, 6.4 Hz, 1H), 4.71 (d, J = 6.4 Hz, 2H), 2.14 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 144.0, 136.8, 133.3, 129.3, 128.6, 128.5, 127.5, 127.3, 126.7, 126.4, 57.9.

実験例２
基質であるアリル化合物（(E)-1,7-Diphenylhept-4-en-3-yl acetate）は、文献Ａに従い合成した。
生成物のアリルアミン：(E)-1,7-Diphenylhept-4-en-3-amine (2b). 1H NMR (400 MHz, CDCl3): δ 7.30-7.15 (m, 10H), 5.56 (dt, J =16.0, 6.4 Hz, 1H), 5.39 (dd, J = 16.0, 7.2 Hz, 1H), 3.25 (dt, J = 7.2, 6.8 Hz, 1H), 2.70 (t, J = 7.8 Hz, 1H), 2.58 (t, J = 8.0 Hz, 1H), 2.36 (dt, J = 7.2, 8.0 Hz, 2H), 1.69 (m, 2H), 1.33 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ 142.2, 141.7, 135.5, 129.5, 128.4, 128.3, 128.2, 128.2, 125.8, 125.7, 53.4, 39.4, 35.7, 34.0, 32.4. IR (neat): 3365 (N-H), 3026, 2924, 1603 (N-H), 970, 746, 699 cm-1. HRMS (ESI): calcd for C19H24N+ (M+H+) 266.1903, found 266.1897. Experimental example 2
The allyl compound ((E) -1,7-Diphenylhept-4-en-3-yl acetate) as a substrate was synthesized according to Document A.
Product Allylamine: (E) -1,7-Diphenylhept-4-en-3-amine (2b). 1 H NMR (400 MHz, CDCl 3 ): δ 7.30-7.15 (m, 10H), 5.56 (dt , J = 16.0, 6.4 Hz, 1H), 5.39 (dd, J = 16.0, 7.2 Hz, 1H), 3.25 (dt, J = 7.2, 6.8 Hz, 1H), 2.70 (t, J = 7.8 Hz, 1H) , 2.58 (t, J = 8.0 Hz, 1H), 2.36 (dt, J = 7.2, 8.0 Hz, 2H), 1.69 (m, 2H), 1.33 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 142.2, 141.7, 135.5, 129.5, 128.4, 128.3, 128.2, 128.2, 125.8, 125.7, 53.4, 39.4, 35.7, 34.0, 32.4. IR (neat): 3365 (NH), 3026, 2924, 1603 (NH ), 970, 746, 699 cm -1 .HRMS (ESI): calcd for C 19 H 24 N + (M + H + ) 266.1903, found 266.1897.

実験例３
基質であるアリル化合物（2-Phenyl-3-[(methoxycarbonyl)oxy]-1-cyclohexene）は、文献Ｂ（Mori, M.; Kuroda, S.; Zhang, C.-S.; Sato, Y. J. Org. Chem. 1997, 62, 3263.）に従い合成した。
生成物のアリルアミン：2-Phenylcyclohex-2-enamine (2c). 1H NMR (400 MHz, CDCl3): δ 7.37-7.22 (m, 5H), 5.98 (appt, J = 4.0, 1H), 3.94 (brm, 1H), 2.21-2.15 (m, 2H), 1.99-1.93 (m, 2H), 1.77-1.64 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 141.7, 141.2, 128.4, 126.8, 126.7, 126.2, 46.6, 32.3, 26.0, 18.2. IR (neat): 3366 (N-H), 2929, 1597 (N-H), 1493, 1443, 761, 698 cm-1. HRMS (ESI): calcd for C12H16N+ (M+H+) 174.1277, found 174.1271. Experimental example 3
The allyl compound (2-Phenyl-3-[(methoxycarbonyl) oxy] -1-cyclohexene), which is a substrate, can be found in Document B (Mori, M .; Kuroda, S .; Zhang, C.-S .; Sato, YJ Org Chem. 1997, 62, 3263.).
Product Allylamine: 2-Phenylcyclohex-2-enamine (2c). 1 H NMR (400 MHz, CDCl 3 ): δ 7.37-7.22 (m, 5H), 5.98 (appt, J = 4.0, 1H), 3.94 ( . brm, 1H), 2.21-2.15 ( m, 2H), 1.99-1.93 (m, 2H), 1.77-1.64 (m, 2H) 13 C NMR (100 MHz, CDCl 3): δ 141.7, 141.2, 128.4, 126.8, 126.7, 126.2, 46.6, 32.3, 26.0, 18.2. IR (neat): 3366 (NH), 2929, 1597 (NH), 1493, 1443, 761, 698 cm -1 .HRMS (ESI): calcd for C 12 H 16 N + (M + H + ) 174.1277, found 174.1271.

実験例４
基質であるアリル化合物（2-(4-Methoxyphenyl)-3-[(methoxycarbonyl)oxy]-1-cyclohexene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-(4-Methoxyphenyl)cyclohex-2-enamine (2d). 1H NMR (400 MHz, CDCl3): δ 7.31 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 5.89 (appt, J = 4.0 Hz, 1H), 3.89 (brm, 1H), 3.81 (s, 3H), 2.18-2.15 (m, 2H), 1.95-1.91 (m, 1H), 1.75-1.65 (m, 3H), 1.41 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ 158.5, 140.9, 133.6, 127.1, 125.3, 113.7, 55.2, 46.6, 32.3, 26.0, 18.1. IR (neat): 3369 (N-H), 2931, 1606 (N-H), 1511, 1247 (C-O-C), 1180, 1038 (C-O-C), 836, 808 cm-1. HRMS (ESI): calcd for C13H18NO+ (M+H+) 204.1383, found 204.1386. Experimental Example 4
The substrate allyl compound (2- (4-Methoxyphenyl) -3-[(methoxycarbonyl) oxy] -1-cyclohexene) was synthesized according to Document B.
Product Allylamine: 2- (4-Methoxyphenyl) cyclohex-2-enamine (2d). 1 H NMR (400 MHz, CDCl 3 ): δ 7.31 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 5.89 (appt, J = 4.0 Hz, 1H), 3.89 (brm, 1H), 3.81 (s, 3H), 2.18-2.15 (m, 2H), 1.95-1.91 (m, 1H) , 1.75-1.65 (m, 3H), 1.41 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 158.5, 140.9, 133.6, 127.1, 125.3, 113.7, 55.2, 46.6, 32.3, 26.0, 18.1 IR (neat): 3369 (NH), 2931, 1606 (NH), 1511, 1247 (COC), 1180, 1038 (COC), 836, 808 cm -1 .HRMS (ESI): calcd for C 13 H 18 NO + (M + H + ) 204.1383, found 204.1386.

実験例５
基質であるアリル化合物（2-(3-Nitrophenyl)-3-[(methoxycarbonyl)oxy]-1-cyclohexene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-(3-Nitrophenyl)cyclohex-2-enamine (2e). 1H NMR (400 MHz, CDCl3): δ8.29 (m, 1H), 8.10-8.07 (m, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.49 (m, 1H), 6.14 (appt, J = 4.0 Hz, 1H), 3.95 (brm, 1H), 2.31-2.16 (m, 2H), 2.01-1.92 (m, 1H), 1.84-1.66 (m, 3H), 1.33 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ148.3, 143.0, 139.4, 132.1, 129.6, 129.2, 121.5, 121.0, 46.5, 32.8, 26.0, 17.5. IR (neat): 3374 (N-H), 2930, 1525 (N-O), 1348 (N-O), 803, 739 cm-1. HRMS (ESI): calcd for C12H15N2O2 + (M+H+) 219.1128, found 219.1141. Experimental Example 5
The substrate allyl compound (2- (3-Nitrophenyl) -3-[(methoxycarbonyl) oxy] -1-cyclohexene) was synthesized according to Document B.
Product Allylamine: 2- (3-Nitrophenyl) cyclohex-2-enamine (2e). 1 H NMR (400 MHz, CDCl 3 ): δ8.29 (m, 1H), 8.10-8.07 (m, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.49 (m, 1H), 6.14 (appt, J = 4.0 Hz, 1H), 3.95 (brm, 1H), 2.31-2.16 (m, 2H), 2.01-1.92 . (m, 1H), 1.84-1.66 (m, 3H), 1.33 (brs, 2H) 13 C NMR (100 MHz, CDCl 3): δ148.3, 143.0, 139.4, 132.1, 129.6, 129.2, 121.5, 121.0 , 46.5, 32.8, 26.0, 17.5. IR (neat): 3374 (NH), 2930, 1525 (NO), 1348 (NO), 803, 739 cm -1 . HRMS (ESI): calcd for C 12 H 15 N 2 O 2 + (M + H + ) 219.1128, found 219.1141.

実験例６
基質であるアリル化合物（2-{3,5-Bis(trifluoromethyl)phenyl}-3-[(methoxycarbony)oxy]-1-cyclohexene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-{3,5-Bis(trifluoromethyl)phenyl}cyclohex-2-enamine (2f). 1H NMR (400 MHz, CDCl3): δ7.88 (s, 2H), 7.74 (s, 1H), 6.16 (appt, J = 3.8 Hz, 1H), 3.93-3.92 (brm, 1H), 2.30-2.20 (m, 2H), 2.00-1.93 (m, 1H), 1.81-1.69 (m, 3H), 1.34 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ143.5, 139.1, 131.5 (q, JCF = 33 Hz), 126.3, 123.4 (q, JCF = 273 Hz), 120.43 (m), 46.7, 32.8, 26.0, 17.4. IR (neat): 3379, 2935, 1384, 1281, 1173, 1133, 895, 685 cm-1. HRMS (ESI): calcd for C14H14F6N+ (M+H+) 310.1025, found 310.1027. Experimental Example 6
The substrate allyl compound (2- {3,5-Bis (trifluoromethyl) phenyl} -3-[(methoxycarbony) oxy] -1-cyclohexene) was synthesized according to Document B.
Product Allylamine: 2- {3,5-Bis (trifluoromethyl) phenyl} cyclohex-2-enamine (2f). 1 H NMR (400 MHz, CDCl 3 ): δ7.88 (s, 2H), 7.74 (s , 1H), 6.16 (appt, J = 3.8 Hz, 1H), 3.93-3.92 (brm, 1H), 2.30-2.20 (m, 2H), 2.00-1.93 (m, 1H), 1.81-1.69 (m, 3H .), 1.34 (brs, 2H ) 13 C NMR (100 MHz, CDCl 3): δ143.5, 139.1, 131.5 (q, J CF = 33 Hz), 126.3, 123.4 (q, J CF = 273 Hz), 120.43 (m), 46.7, 32.8, 26.0, 17.4. IR (neat): 3379, 2935, 1384, 1281, 1173, 1133, 895, 685 cm -1 .HRMS (ESI): calcd for C 14 H 14 F 6 N + (M + H + ) 310.1025, found 310.1027.

実験例７
基質であるアリル化合物（2-(3-Phenylpropyl)-3-[(methoxycarbonyl)oxy]-1-cyclohexene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-(3-Phenylpropyl)cyclohex-2-enamine (2g). 1H NMR (400 MHz, CDCl3): δ7.29-7.16 (m, 5H), 5.46 (brm, 1H), 3.22 (brm, 1H), 2.67-2.55 (m, 2H), 2.21-1.51 (m, 10H), 1.35 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ142.5, 140.1, 128.4, 128.2, 125.6, 123.3, 47.8, 35.6, 33.9, 33.0, 29.7, 25.4, 18.5. IR (neat): 3367 (N-H), 2928, 1603 (N-H), 1496, 1453, 1076, 749, 699 cm-1. HRMS (ESI): calcd for C15H22N+ (M+H+) 216.1747, found 216.1742. Experimental Example 7
The substrate allyl compound (2- (3-Phenylpropyl) -3-[(methoxycarbonyl) oxy] -1-cyclohexene) was synthesized according to Document B.
Product Allylamine: 2- (3-Phenylpropyl) cyclohex-2-enamine (2g). 1 H NMR (400 MHz, CDCl 3 ): δ7.29-7.16 (m, 5H), 5.46 (brm, 1H), 3.22 (brm, 1H), 2.67-2.55 (m, 2H), 2.21-1.51 (m, 10H), 1.35 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ142.5, 140.1, 128.4 , 128.2, 125.6, 123.3, 47.8, 35.6, 33.9, 33.0, 29.7, 25.4, 18.5.IR (neat): 3367 (NH), 2928, 1603 (NH), 1496, 1453, 1076, 749, 699 cm -1 HRMS (ESI): calcd for C 15 H 22 N + (M + H + ) 216.1747, found 216.1742.

実験例８
基質であるアリル化合物（N-p-Toluensulfonyl-5-methoxycarbonyl-3-piperidene）は、文献Ｃ（Takahata, H.; Suto, Y.; Kato, E.; Yoshimura, Y.; Ouchi, H. Adv. Synth. Catal. 2007, 349, 685.）に従い合成した。
生成物のアリルアミン：1,2,3,6-Tetrahydro-1-tosylpyridin-3-amine (2h). 1H NMR (400 MHz, CDCl3): δ7.67 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 5.80-5.76 (m, 1H), 5.70-5.6 (m, 1H), 3.63-3.58 (m, 1H), 3.47-3.42 (m, 2H), 3.21 (dd, J = 12.0, 4.0 Hz, 1H), 2.94 (dd, J = 12.0, 4.0 Hz, 1H), 2.44 (s, 3H), 1.38 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ143.6, 132.9, 130.1, 129.6, 127.5, 123.5, 51.4, 46.0, 44.7, 21.4. IR (neat): 3371 (N-H), 3036, 2839, 1597 (N-H), 1455, 1345 (S=O), 1165 (S=O), 1092, 970, 819, 684, 571, 550 cm-1. HRMS (ESI): calcd for C12H17O2N2S+ (M+H+) 253.1005, found 253.1007. Experimental Example 8
The substrate allyl compound (Np-Toluensulfonyl-5-methoxycarbonyl-3-piperidene) is document C (Takahata, H .; Suto, Y .; Kato, E .; Yoshimura, Y .; Ouchi, H. Adv. Synth). Catal. 2007, 349, 685.).
Product Allylamine: 1,2,3,6-Tetrahydro-1-tosylpyridin-3-amine (2h). 1 H NMR (400 MHz, CDCl 3 ): δ7.67 (d, J = 8.0 Hz, 2H) , 7.34 (d, J = 8.0 Hz, 2H), 5.80-5.76 (m, 1H), 5.70-5.6 (m, 1H), 3.63-3.58 (m, 1H), 3.47-3.42 (m, 2H), 3.21 (dd, J = 12.0, 4.0 Hz, 1H), 2.94 (dd, J = 12.0, 4.0 Hz, 1H), 2.44 (s, 3H), 1.38 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ143.6, 132.9, 130.1, 129.6, 127.5, 123.5, 51.4, 46.0, 44.7, 21.4. IR (neat): 3371 (NH), 3036, 2839, 1597 (NH), 1455, 1345 (S = O ), 1165 (S = O), 1092, 970, 819, 684, 571, 550 cm -1 .HRMS (ESI): calcd for C 12 H 17 O 2 N 2 S + (M + H + ) 253.1005, found 253.1007.

実験例９
基質であるアリル化合物（2-Phenyl-3-[(methoxycarbonyl)oxy]-1-cyclopentene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-Phenylcyclopent-2-enamine (2i). 1H NMR (500 MHz, CDCl3): δ7.47-7.23 (m, 5H), 6.12 (brm, 1H), 4.42-4.41 (m, 1H), 2.62-2.56 (m, 1H), 2.46-2.39 (m, 2H), 1.75-1.71 (m, 1H), 1.48 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ146.6, 135.4, 128.6, 127.7, 127.1, 126.1, 57.3, 34.2, 30.4. IR (KBr): 3390 (N-H), 2931, 1606 (N-H), 1561, 1465, 1369, 1345, 756, 693 cm-1. HRMS (ESI): calcd for C11H14N+ (M+H+) 160.1121, found 160.1129. Experimental Example 9
The allyl compound (2-Phenyl-3-[(methoxycarbonyl) oxy] -1-cyclopentene) as a substrate was synthesized according to Document B.
Product Allylamine: 2-Phenylcyclopent-2-enamine (2i). 1 H NMR (500 MHz, CDCl 3 ): δ7.47-7.23 (m, 5H), 6.12 (brm, 1H), 4.42-4.41 (m , 1H), 2.62-2.56 (m, 1H), 2.46-2.39 (m, 2H), 1.75-1.71 (m, 1H), 1.48 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ146 .6, 135.4, 128.6, 127.7, 127.1, 126.1, 57.3, 34.2, 30.4.IR (KBr): 3390 (NH), 2931, 1606 (NH), 1561, 1465, 1369, 1345, 756, 693 cm -1 HRMS (ESI): calcd for C 11 H 14 N + (M + H + ) 160.1121, found 160.1129.

実験例１０
基質であるアリル化合物（2-Phenyl-3-[(methoxycarbonyl)oxy]-1-cycloheptene）は、文献Ｂに従い合成した。
生成物のアリルアミン：2-Phenylcyclohept-2-enamine (2j). 1H NMR (400 MHz, CDCl3): δ7.33-7.20 (m, 5H), 5.89 (dd, J = 6.0, 7.2 Hz, 1H), 4.02-4.00 (m, 1H), 2.37-2.27 (m, 2H), 2.03-1.69 (m, 5H), 1.62-1.55 (m, 1H), 1.40 (brs, 2H). 13C NMR (100 MHz, CDCl3): δ 144.8, 144.1, 130.1, 128.0, 126.6, 126.5, 54.1, 34.0, 27.5, 27.0, 24.9. IR (neat): 3370 (N-H), 2923, 2850, 1598 (N-H), 1489, 1443, 757, 699 cm-1. HRMS (ESI): calcd for C13H18N+ (M+H+) 188.1434, found 188.1442. Experimental Example 10
The allyl compound (2-Phenyl-3-[(methoxycarbonyl) oxy] -1-cycloheptene) as a substrate was synthesized according to Document B.
Product Allylamine: 2-Phenylcyclohept-2-enamine (2j). 1 H NMR (400 MHz, CDCl 3 ): δ7.33-7.20 (m, 5H), 5.89 (dd, J = 6.0, 7.2 Hz, 1H ), 4.02-4.00 (m, 1H), 2.37-2.27 (m, 2H), 2.03-1.69 (m, 5H), 1.62-1.55 (m, 1H), 1.40 (brs, 2H). 13 C NMR (100 MHz, CDCl 3 ): δ 144.8, 144.1, 130.1, 128.0, 126.6, 126.5, 54.1, 34.0, 27.5, 27.0, 24.9.IR (neat): 3370 (NH), 2923, 2850, 1598 (NH), 1489, 1443, 757, 699 cm -1 .HRMS (ESI): calcd for C 13 H 18 N + (M + H + ) 188.1434, found 188.1442.

＜実施例２＞
不斉アリル位アミノ化反応の実施例
1,3-ジフェニルアリルアセテート（76 mg, 0.3 mmol）及び (R)-BINAP (15 mg, 0.024 mmol)を1,4-ジオキサン（4.0 mL）及びアンモニア水(2.5 mL)に溶解し、基質溶液を調整した。一方、[PdCl(h3-allyl)]2 (5.5 mg, 0.015 mmol)と(R)-binap (22 mg, 0.036 mmol)とを、1,4-ジオキサン(1.0 mL)中で５分撹拌し、この溶液を基質溶液に投入し、反応液を室温にて１８時間撹拌後、飽和炭酸水素ナトリウム水溶液 (5.0 mL)を加えて希釈した。この希釈液をジクロロメタンで抽出する工程を３回繰り返し、有機層を無水硫酸マグネシウムで乾燥後、ろ過、減圧濃縮し、粗生成物を得た。
粗生成物を、薄層クロマトグラフィー（展開溶媒：n-ヘキサン／イソプロピルアミン＝１９／１）により精製し、目的とする生成物である(R)-1,3-ジフェニルアリルアミン (44.4 mg, 0.21 mmol)を収率７１％で得た。生成物の[a]D 16 = +38.2 (c 0.86, CH2Cl2)であった。ここで、エナンチオマー過剰率は以下の分析条件を用いて決定した。 HPLC (Chiralpak AS-H, Hexane/i-PrOH/Et2NH = 95/5/0.05, flow rate 1.0 mL/min, UV detection at 254 nm) tR = 10.9 min (S), tR = 12.4 min (R). <Example 2>
Examples of asymmetric allylic amination reaction
Dissolve 1,3-diphenylallyl acetate (76 mg, 0.3 mmol) and (R) -BINAP (15 mg, 0.024 mmol) in 1,4-dioxane (4.0 mL) and aqueous ammonia (2.5 mL). Adjusted. On the other hand, [PdCl (h 3 -allyl)] 2 (5.5 mg, 0.015 mmol) and (R) -binap (22 mg, 0.036 mmol) were stirred in 1,4-dioxane (1.0 mL) for 5 minutes. This solution was poured into a substrate solution, and the reaction solution was stirred at room temperature for 18 hours, and then diluted with a saturated aqueous sodium hydrogen carbonate solution (5.0 mL). The process of extracting this diluted solution with dichloromethane was repeated three times. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a crude product.
The crude product was purified by thin layer chromatography (developing solvent: n-hexane / isopropylamine = 19/1), and the desired product (R) -1,3-diphenylallylamine (44.4 mg, 0.21 mmol) was obtained in 71% yield. The product was [a] D 16 = +38.2 (c 0.86, CH 2 Cl 2 ). Here, the enantiomeric excess was determined using the following analytical conditions. HPLC (Chiralpak AS-H, Hexane / i-PrOH / Et 2 NH = 95/5 / 0.05, flow rate 1.0 mL / min, UV detection at 254 nm) t R = 10.9 min (S), t R = 12.4 min (R).

Claims (2)

パラジウム触媒の存在下、液相で下式（化１）
Figure 2010229079
 （式中、Ｒはアルキル基、アルキレン基、又はアリール基を表し、Ｒ１は水素原子、アルキル基又はアリール基を表し、ＸはＯＣＯＲ２又はＯＣＯ２Ｒ２を表す。但し、Ｒ２は炭素数１〜１０のアルキル基、アラルキル基、又はアリール基）で表されるアリルアセテートまたはアリルカーボネートと、アンモニア（ＮＨ３）とを反応させる第１級アリルアミン化合物を製造する方法。 In the presence of a palladium catalyst, in the liquid phase:
Figure 2010229079
 (In the formula, R represents an alkyl group, an alkylene group, or an aryl group, R 1 represents a hydrogen atom, an alkyl group, or an aryl group, and X represents OCOR 2 or OCO 2 R 2 , where R 2 represents carbon. A method for producing a primary allylamine compound in which allyl acetate or allyl carbonate represented by an alkyl group, an aralkyl group, or an aryl group of formulas 1 to 10 is reacted with ammonia (NH 3 ). 前記アンモニア（ＮＨ３）としてアンモニア水を使用し、ジオキサン中で反応させる請求項１に記載の方法。 The method according to claim 1, wherein ammonia water is used as the ammonia (NH 3 ) and the reaction is carried out in dioxane.
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Publication number Priority date Publication date Assignee Title
CN114436859A (en) * 2020-11-02 2022-05-06 中国石油化工股份有限公司 Method for preparing sec-butylamine through etherified C4
CN114436826A (en) * 2020-11-02 2022-05-06 中国石油化工股份有限公司 Method for preparing sec-butylamine through post-etherification C4 by supergravity method

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JPS4920162B1 (en) * 1970-06-25 1974-05-23
JPH01153660A (en) * 1987-12-11 1989-06-15 Showa Denko Kk Production of allyl-type amine
JP2004107340A (en) * 2002-08-30 2004-04-08 Mitsubishi Chemicals Corp Method for producing allyl compound

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Publication number Priority date Publication date Assignee Title
JPS4920162B1 (en) * 1970-06-25 1974-05-23
JPH01153660A (en) * 1987-12-11 1989-06-15 Showa Denko Kk Production of allyl-type amine
JP2004107340A (en) * 2002-08-30 2004-04-08 Mitsubishi Chemicals Corp Method for producing allyl compound

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114436859A (en) * 2020-11-02 2022-05-06 中国石油化工股份有限公司 Method for preparing sec-butylamine through etherified C4
CN114436826A (en) * 2020-11-02 2022-05-06 中国石油化工股份有限公司 Method for preparing sec-butylamine through post-etherification C4 by supergravity method

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