JP2008184418A - Palladium catalyst and method for producing biaryl-based compound or heterobiaryl-based compound using it - Google Patents
Palladium catalyst and method for producing biaryl-based compound or heterobiaryl-based compound using it Download PDFInfo
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Abstract
Description
本発明は、鈴木−宮浦カップリングに用いられるパラジウム触媒と、このパラジウム触媒を用いたビアリール系化合物又はヘテロビアリール系化合物の製造方法に関する。 The present invention relates to a palladium catalyst used for Suzuki-Miyaura coupling and a method for producing a biaryl compound or heterobiaryl compound using the palladium catalyst.
鈴木−宮浦カップリングは、高機能性有機素材合成に多用される極めて重要な反応である。この反応は主として、芳香族ハロゲン化物又はヘテロ芳香族ハロゲン化物と芳香族ボロン酸とをカップリングさせてビアリール系化合物を合成するために利用されている。なお、この反応は、テトラヒドロフランなどの有機溶剤中で行われ、パラジウム触媒、この触媒を活性化、安定化させるための配位子、反応中に生成する酸を中和する塩基が必要とされる。 The Suzuki-Miyaura coupling is an extremely important reaction frequently used for the synthesis of highly functional organic materials. This reaction is mainly used for synthesizing a biaryl compound by coupling an aromatic halide or heteroaromatic halide and an aromatic boronic acid. This reaction is carried out in an organic solvent such as tetrahydrofuran, and a palladium catalyst, a ligand for activating and stabilizing the catalyst, and a base for neutralizing the acid generated during the reaction are required. .
しかし、パラジウム触媒は反応中に失活しやすく、反応にある程度の触媒量が必要とされる。また、パラジウム触媒は高価である。したがって、製造コストを削減させるために、触媒量の低減化が望まれていた。また、パラジウム触媒はクラスター化してしまうため、反応後にリサイクル使用することもできないという問題があった。 However, the palladium catalyst is easily deactivated during the reaction, and a certain amount of catalyst is required for the reaction. Further, the palladium catalyst is expensive. Therefore, a reduction in the amount of catalyst has been desired in order to reduce manufacturing costs. In addition, since the palladium catalyst is clustered, there is a problem that it cannot be recycled after the reaction.
また、使用する配位子は有機リン系のものがほとんどで、高価かつ毒性もある。さらに、有機溶剤の使用も環境対応度の観点から好ましいものではなかった。 In addition, most of the ligands used are organophosphorus based, and are expensive and toxic. Furthermore, the use of an organic solvent is not preferable from the viewpoint of environmental compatibility.
なお、反応後のパラジウム触媒のリサイクル使用に関し、非特許文献１には、ヒドロキシアパタイト固定化パラジウム触媒が、ブロモベンゼンとフェニルホウ酸を用いた鈴木−宮浦カップリングに活性を示し、触媒回転効率（ＴＯＮ）も高いことが示されているが、触媒の活性がやや低く、反応温度１２０℃という厳しい反応条件が必要であるという欠点があった。 Regarding the recycling of the palladium catalyst after the reaction, Non-Patent Document 1 discloses that a hydroxyapatite-immobilized palladium catalyst is active in the Suzuki-Miyaura coupling using bromobenzene and phenylboric acid, and the catalyst rotation efficiency (TON) ) Is also high, but the activity of the catalyst is somewhat low, and there is a drawback that severe reaction conditions of a reaction temperature of 120 ° C. are necessary.
また、非特許文献２には、配位子としてアリールホスフィンを有する非架橋性両親媒性高分子を用いた固相パラジウム触媒が鈴木−宮浦カップリングに活性を示し、ＴＯＮも高いことが示されているが、非特許文献１と同様、反応温度１００℃という厳しい反応条件が必要である。さらに、非架橋性両親媒性高分子を作成するためのコストが高いという欠点があった。
そこで、本発明は、活性が高く、温和な反応条件で、かつ、少量の使用であっても収率よく鈴木−宮浦カップリングを進行させることができ、さらに、触媒回収効率が高く、安価で毒性が低く、有機溶剤の使用量を削減することのできる、新規のパラジウム触媒を提供することを目的とする。また、このパラジウム触媒を用いて、高収率でビアリール系化合物を製造することのできる、新規のビアリール系化合物又はヘテロビアリール系化合物の製造方法を提供することを目的とする。 Therefore, the present invention has a high activity, can be allowed to proceed with the Suzuki-Miyaura coupling in a good yield under mild reaction conditions and in a small amount of use, and has a high catalyst recovery efficiency and is inexpensive. An object of the present invention is to provide a novel palladium catalyst having low toxicity and capable of reducing the amount of organic solvent used. Another object of the present invention is to provide a novel biaryl compound or heterobiaryl compound production method capable of producing a biaryl compound with high yield using this palladium catalyst.
上記課題を解決するために鋭意検討した結果、酢酸パラジウムをイオン液体［ｂｍｉｍ］ＰＦ６に溶解し、ジエチルアミノプロピル残基で表面修飾した無定形アルミナの空孔内に固定化することで、鈴木−宮浦カップリングを収率よく進行させることのできるパラジウム触媒が得られることを見出し、本発明に想到した。 As a result of diligent investigations to solve the above-mentioned problems, by dissolving palladium acetate in the ionic liquid [bmim] PF 6 and immobilizing it in the pores of amorphous alumina surface-modified with diethylaminopropyl residue, Suzuki- The inventors have found that a palladium catalyst capable of allowing Miyaura coupling to proceed with good yield is obtained, and have arrived at the present invention.
すなわち、本発明の請求項１記載のビアリール系化合物又はヘテロビアリール系化合物の製造方法は、パラジウム触媒及び塩基の存在下において、芳香族ハロゲン化物又はヘテロ芳香族ハロゲン化物と芳香族ボロン酸又はヘテロ芳香族ボロン酸とを反応させてビアリール系化合物又はヘテロビアリール系化合物を製造するに際し、前記パラジウム触媒として、イオン液体に溶解したパラジウム化合物を多孔質担体に固定化させてなるパラジウム触媒を用いることを特徴とする。 That is, the method for producing a biaryl compound or heterobiaryl compound according to claim 1 of the present invention comprises an aromatic halide or heteroaromatic halide and an aromatic boronic acid or heteroaromatic compound in the presence of a palladium catalyst and a base. When producing a biaryl compound or heterobiaryl compound by reacting with a group boronic acid, a palladium catalyst obtained by immobilizing a palladium compound dissolved in an ionic liquid on a porous carrier is used as the palladium catalyst. And
本発明の請求項２記載のビアリール系化合物又はヘテロビアリール系化合物の製造方法は、請求項１記載において、前記パラジウム触媒として、１−ブチル−３−メチルイミダゾリウムヘキサフルオロホスフェートに溶解した酢酸パラジウムをジエチルアミノプロピル残基で表面修飾した多孔質の無定形アルミナの空孔内に固定化させてなるパラジウム触媒を用いることを特徴とする。 The method for producing a biaryl compound or heterobiaryl compound according to claim 2 of the present invention is the method according to claim 1, wherein palladium acetate dissolved in 1-butyl-3-methylimidazolium hexafluorophosphate is used as the palladium catalyst. It is characterized by using a palladium catalyst which is immobilized in pores of porous amorphous alumina whose surface is modified with a diethylaminopropyl residue.
本発明の請求項３記載のビアリール系化合物又はヘテロビアリール系化合物の製造方法は、請求項１又は２において、前記塩基は炭酸カリウムであることを特徴とする。 The method for producing a biaryl compound or heterobiaryl compound according to claim 3 of the present invention is characterized in that, in claim 1 or 2, the base is potassium carbonate.
本発明の請求項４記載のビアリール系化合物又はヘテロビアリール系化合物の製造方法は、請求項１〜３のいずれか１項において、前記芳香族ハロゲン化物と芳香族ボロン酸との反応が、水とエタノールの混合溶媒中において行われることを特徴とする。 The method for producing a biaryl compound or heterobiaryl compound according to claim 4 of the present invention is the method according to any one of claims 1 to 3, wherein the reaction between the aromatic halide and the aromatic boronic acid is carried out with water. It is characterized by being carried out in a mixed solvent of ethanol.
本発明の請求項５記載のパラジウム触媒は、１−ブチル−３−メチルイミダゾリウムヘキサフルオロホスフェートに溶解した酢酸パラジウムをジエチルアミノプロピル残基で表面修飾した多孔質の無定形アルミナの空孔内に固定化させてなることを特徴とする。 The palladium catalyst according to claim 5 of the present invention is fixed in the pores of porous amorphous alumina obtained by surface modification of palladium acetate dissolved in 1-butyl-3-methylimidazolium hexafluorophosphate with a diethylaminopropyl residue. It is characterized by being made.
本発明によれば、活性が高く、温和な反応条件で、かつ、少量の使用であっても収率よく鈴木−宮浦カップリングを進行させることができ、さらに、触媒回収効率が高く、安価で毒性が低く、有機溶剤の使用量を削減することができる、新規のパラジウム触媒が提供される。また、このパラジウム触媒を用いて、高収率でビアリール系化合物又はヘテロビアリール系化合物を製造することができる、新規のビアリール系化合物又はヘテロビアリール系化合物の製造方法が提供される。 According to the present invention, the Suzuki-Miyaura coupling can proceed with high yield under high reaction conditions under mild reaction conditions and even with a small amount of use. Furthermore, the catalyst recovery efficiency is high and inexpensive. Provided is a novel palladium catalyst having low toxicity and capable of reducing the amount of organic solvent used. Moreover, the manufacturing method of the novel biaryl type compound or heterobiaryl type compound which can manufacture a biaryl type compound or a heterobiaryl type compound with a high yield using this palladium catalyst is provided.
本発明のパラジウム触媒は、パラジウム化合物を多孔質担体に固定化させたものである。 The palladium catalyst of the present invention is obtained by immobilizing a palladium compound on a porous carrier.
ここで、パラジウム化合物には、酢酸パラジウム（Ｐｄ（ＯＡｃ）２、ここで（ＯＡｃ）は酢酸残基）、塩化パラジウム（ＰｄＣｌ２）などのパラジウム塩、パラジウムブラック（Ｐｄ）、テトラ（トリフェニルホスフィン）パラジウム（Ｐｄ（ＰＰｈ３）４、ここでＰｈはフェニル基）などのパラジウム錯体など、一般に知られているパラジウム化合物が含まれる。これらの中では、特に酢酸パラジウムが好適に用いられる。 Here, palladium compounds include palladium acetate (Pd (OAc) 2 , where (OAc) is an acetic acid residue), palladium salts such as palladium chloride (PdCl 2 ), palladium black (Pd), tetra (triphenylphosphine). Generally known palladium compounds such as palladium complexes such as palladium (Pd (PPh 3 ) 4 , where Ph is a phenyl group) are included. Of these, palladium acetate is particularly preferably used.
また、多孔質担体としては、特定のものに限定されず、アルミナ、チタニア、シリカ、ゼオライト、アパタイト、ヒドロキシアパタイトなどからなる一般的な多孔質固体を用いることができる。さらに、これらの形状も限定されず、無定形の多孔質担体、ハニカム状に成形したものなどを用いることができるが、好ましくは、無定形のものが用いられる。 The porous carrier is not limited to a specific one, and a general porous solid made of alumina, titania, silica, zeolite, apatite, hydroxyapatite, or the like can be used. Furthermore, these shapes are not limited, and an amorphous porous carrier or a honeycomb-shaped one can be used, but an amorphous one is preferably used.
また、多孔質担体としてアルミナを用いる場合は、一般的に触媒の担体として使用される逆相アルミナが好適に用いられ、さらに好ましくは、アミノ置換シラン化合物により前処理されたものが用いられる。アミノ置換シラン化合物としては、特定のものに限定されるものではないが、例えば、３−（トリメトキシシリル）−Ｎ，Ｎ−ジエチルアミン（（Ｃ２Ｈ５）ＨＮ（ＣＨ２）２Ｓｉ（ＯＣＨ３）３）などが好適に用いられる。 When alumina is used as the porous carrier, reverse phase alumina generally used as a catalyst carrier is preferably used, and more preferably pretreated with an amino-substituted silane compound. The amino-substituted silane compound is not limited to a specific one. For example, 3- (trimethoxysilyl) -N, N-diethylamine ((C 2 H 5 ) HN (CH 2 ) 2 Si (OCH) 3 ) 3 ) and the like are preferably used.
そして、パラジウム化合物は、イオン液体に溶解した状態で逆相アルミナの空孔内に固定化されている。イオン液体としては、常温、好ましくは３５℃以下で液体であって、パラジウム化合物を溶解できるものであればよく、１−ブチル−３−メチルイミダゾリウムヘキサフルオロホスフェート（［ｂｍｉｍ］ＰＦ６）、１−ヘキシル−３−メチルイミダゾリウムヘキサフルオロホスフェート（［ｈｍｉｍ］ＰＦ６）、１−ブチル−３−メチルイミダゾリウムビストリフルオロメタンスルフォニルアミド（［ｂｍｉｍ］ＮＴｆ２）などを用いることができるが、［ｂｍｉｍ］ＰＦ６が特に好適に用いられる。 And the palladium compound is fixed in the void | hole of reverse phase alumina in the state melt | dissolved in the ionic liquid. The ionic liquid may be any liquid as long as it is liquid at room temperature, preferably 35 ° C. or less and can dissolve the palladium compound, such as 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF 6 ), 1 -Hexyl-3-methylimidazolium hexafluorophosphate ([him] PF 6 ), 1-butyl-3-methylimidazolium bistrifluoromethanesulfonylamide ([bmim] NTf 2 ), etc. can be used, but [bmim PF 6 is particularly preferably used.
本発明のビアリール系化合物の製造方法は、パラジウム触媒及び塩基の存在下において、芳香族ハロゲン化物又はヘテロ芳香族ハロゲン化物と芳香族ボロン酸又はヘテロ芳香族ボロン酸とを反応させてビアリール系化合物を製造するに際し、上記の本発明のパラジウム触媒を用いるものである。なお、芳香族ハロゲン化物、ヘテロ芳香族ハロゲン化物、芳香族ボロン酸、ヘテロ芳香族ボロン酸としては、特定のものに限定されず、あらゆる種類の芳香族ハロゲン化物又はヘテロ芳香族ハロゲン化物と、芳香族ボロン酸又はヘテロ芳香族ボロン酸の組合せにて、鈴木−宮浦カップリングによるビアリール系化合物の製造が可能である。 The method for producing a biaryl compound of the present invention comprises reacting an aromatic halide or heteroaromatic halide with an aromatic boronic acid or heteroaromatic boronic acid in the presence of a palladium catalyst and a base to produce the biaryl compound. In the production, the palladium catalyst of the present invention is used. The aromatic halide, heteroaromatic halide, aromatic boronic acid and heteroaromatic boronic acid are not limited to specific ones, and any kind of aromatic halide or heteroaromatic halide, aromatic Biaryl compounds can be produced by Suzuki-Miyaura coupling with combinations of aromatic boronic acids or heteroaromatic boronic acids.
ここで、塩基としては有機及び無機の塩基を用いることができ、特定のものに限定されないが、特に炭酸カリウムが好適に用いられる。また、芳香族ハロゲン化物と芳香族ボロン酸との反応は通常用いられる有機溶媒中でも進行するが、エタノールと水の混合溶媒中において最も効率よく行われる。 Here, organic and inorganic bases can be used as the base and are not limited to specific ones, but potassium carbonate is particularly preferably used. The reaction between the aromatic halide and the aromatic boronic acid proceeds even in a commonly used organic solvent, but is most efficiently performed in a mixed solvent of ethanol and water.
以上の本発明のパラジウム触媒は、触媒回転効率（ＴＯＮ）が２００万に達する極めて高い活性を示し、濾過により容易に回収されリサイクル可能であり、さらに、既知物質から簡便な操作で調製できる、という利点を有する。また、このパラジウム触媒を用いたビアリール系化合物の製造方法は、反応に配位子を必要とせず、反応はエタノールと水の混合溶媒中で進行して環境対応度が高い。また、反応は室温で進行して加熱の必要がなく、さまざまな化合物を反応させることができる。さらに、均一系の触媒で見られるクラスター化による触媒の失活や触媒による生成物への汚染を防ぐことが可能となる。 The palladium catalyst of the present invention described above exhibits extremely high activity with a catalyst rotation efficiency (TON) reaching 2 million, can be easily recovered by filtration and can be recycled, and can be prepared from a known substance by a simple operation. Have advantages. In addition, this method for producing a biaryl compound using a palladium catalyst does not require a ligand for the reaction, and the reaction proceeds in a mixed solvent of ethanol and water and is highly environmentally friendly. In addition, the reaction proceeds at room temperature and does not require heating, and various compounds can be reacted. Furthermore, it is possible to prevent the catalyst from being deactivated due to clustering and contamination of the product by the catalyst, which is observed in a homogeneous catalyst.
以下、具体的な実施例に基づいて、本発明について詳細に説明する。なお、本発明は、以下の実施例によって制限されるものではない。 Hereinafter, the present invention will be described in detail based on specific examples. In addition, this invention is not restrict | limited by a following example.
［パラジウム触媒の調製］
（１）逆相アルミナの調製
窒素雰囲気下、１２０℃のオーブンで２４時間乾燥したアルミナ（Ａｌ２Ｏ３、日揮化学製、球状、比表面積１５２ｍ２／ｇ、４．７４９ｇ）に３−（トリメトシキシリル）−プロピル−Ｎ，Ｎ−ジエチルアミン（１８８０μｌ、７．５ｍｍｏｌ）、トルエン（３８ｍｌ）を加え、２４時間加熱還流、撹拌した。室温まで冷却した後、デカンテーションにより溶媒と触媒を分離した。残留物を塩化メチレン（ＣＨ２Ｃｌ２）で洗浄し減圧下乾燥させ、生成物（５．０３４ｇ）を得た。
[Preparation of palladium catalyst]
(1) Preparation of reversed-phase alumina 3- (trimethyl) was added to alumina (Al 2 O 3 , JGC Chemical, spherical, specific surface area 152 m 2 / g, 4.749 g) dried in an oven at 120 ° C. for 24 hours under a nitrogen atmosphere. Tosoxysilyl) -propyl-N, N-diethylamine (1880 μl, 7.5 mmol) and toluene (38 ml) were added, and the mixture was heated to reflux and stirred for 24 hours. After cooling to room temperature, the solvent and the catalyst were separated by decantation. The residue was washed with methylene chloride (CH 2 Cl 2 ) and dried under reduced pressure to give the product (5.034 g).
（２）パラジウム触媒の調製
窒素雰囲気下、上記の方法で調製した逆相アルミナ（ＮＤＥＡＰ−Ａｌ２Ｏ３（４．１４１０ｇ））に酢酸パラジウム（Ｐｄ（ＯＡｃ）２（３１．６ｍｇ、０．１４ｍｍｏｌ））と１−ブチル−３−メチルイミダゾリウムヘキサフルオロホスフェート（［ｂｍｉｍ］ＰＦ６（４１９．５ｍｇ、逆相アルミナの１０質量％））のテトラヒドロフラン（ＴＨＦ（２０ｍｌ））溶液を加え4時間攪拌した。ＴＨＦを減圧留去後、逆相アルミナをジエチルエーテル（Ｅｔ２Ｏ）でゆすぎ、減圧下で乾燥し、担持触媒（４．４３１０g）を得た。酢酸パラジウム担持量は０．０３２ｍｍｏｌ／ｇであった。
(2) Preparation of palladium catalyst Under a nitrogen atmosphere, palladium acetate (Pd (OAc) 2 (31.6 mg, 0.14 mmol) was added to the reverse-phase alumina (NDEAP-Al 2 O 3 (4.1410 g)) prepared by the above method. )) And 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim] PF 6 (419.5 mg, 10% by mass of reversed phase alumina)) in tetrahydrofuran (THF (20 ml)) were added and stirred for 4 hours. . After THF was distilled off under reduced pressure, the reverse phase alumina was rinsed with diethyl ether (Et 2 O) and dried under reduced pressure to obtain a supported catalyst (4.4310 g). The amount of palladium acetate supported was 0.032 mmol / g.
［反応条件の検討］
実施例１で得られたパラジウム触媒を用いて、ｐ−ブロモアセトフェノンとフェニルボロン酸の鈴木−宮浦カップリングの反応条件について検討した。
[Examination of reaction conditions]
Using the palladium catalyst obtained in Example 1, the reaction conditions for the Suzuki-Miyaura coupling of p-bromoacetophenone and phenylboronic acid were examined.
（１）塩基の検討
ｐ−ブロモアセトフェノンでは反応が速すぎるため、その代わりにｐ−ブロモアニソールを用いて、反応に用いる塩基について検討した。
(1) Examination of base Since reaction is too fast in p-bromoacetophenone, p-bromoanisole was used instead to examine the base used in the reaction.
ｐ−ブロモアニソールに対して、それぞれ、１．４当量のフェニルボロン酸、０．０５当量のパラジウム触媒、塩基（２．０当量の炭酸カリウム、炭酸ナトリウム、リン酸カリウム、炭酸セシウム、又は１．０当量のジアザビシクロウンデセン（ＤＢＵ））を用い、これらを水、エタノールの１：１の混合溶媒中で混合し、室温で３時間撹拌して反応を進行させた。 For p-bromoanisole, 1.4 equivalents of phenylboronic acid, 0.05 equivalents of palladium catalyst, base (2.0 equivalents of potassium carbonate, sodium carbonate, potassium phosphate, cesium carbonate, or 1. Using 0 equivalent of diazabicycloundecene (DBU)), these were mixed in a 1: 1 mixed solvent of water and ethanol, and stirred at room temperature for 3 hours to proceed the reaction.
反応によって得られた４−メトキシビフェニルの収率は、表１に示すとおりであり、炭酸カリウムを用いたときに最もよい結果が得られた。 The yield of 4-methoxybiphenyl obtained by the reaction is as shown in Table 1, and the best results were obtained when potassium carbonate was used.
つぎに、炭酸ナトリウムの添加量について検討したところ、表２に示すように、ｐ−ブロモアニソールに対して２当量のときが最も収率がよかった。したがって、本実施例において、塩基の添加量は、芳香族ハロゲン化物に対して１．５〜２．５当量とすればよいことがわかった。 Next, when the amount of sodium carbonate added was examined, as shown in Table 2, the yield was the highest when it was 2 equivalents with respect to p-bromoanisole. Therefore, in the present Example, it turned out that the addition amount of a base should just be 1.5-2.5 equivalent with respect to an aromatic halide.
（２）溶媒効果の検討
ｐ−ブロモアセトフェノンに対して、それぞれ、１．４当量のフェニルボロン酸、０．０５当量のパラジウム触媒、２．０当量の炭酸カリウムを用い、これらを種々の溶媒中で混合し、室温で撹拌して反応を進行させた。
(2) Examination of solvent effect For p-bromoacetophenone, 1.4 equivalents of phenylboronic acid, 0.05 equivalents of palladium catalyst, and 2.0 equivalents of potassium carbonate, respectively, were used in various solvents. And stirred at room temperature to allow the reaction to proceed.
反応によって得られた４−アセチルビフェニルの収率と反応時間は、表３に示すとおりであり、エタノールと水の１：１の混合溶媒を用いたときに、短時間で最もよい収率が得られた。 The yield and reaction time of 4-acetylbiphenyl obtained by the reaction are as shown in Table 3, and the best yield can be obtained in a short time when a 1: 1 mixed solvent of ethanol and water is used. It was.
また、ｐ−ブロモアセトフェノンの代わりにｐ−ブロモアニソールを用いて、水とエタノールの混合割合を変化させ、同様に反応を行った。結果は表４、図１に示すとおりであり、水とエタノールの１：１の混合溶媒（エタノール量５０％）を用いたときに、最もよい収率が得られ、つぎに３：１の混合溶媒（エタノール量７５％）を用いたときに高い収率が得られた。そして、混合溶媒中のエタノール量を４０〜８０％とすることで、収率よく反応が進むことがわかった。 Further, p-bromoanisole was used instead of p-bromoacetophenone, and the reaction was carried out in the same manner while changing the mixing ratio of water and ethanol. The results are shown in Table 4 and FIG. 1, and when using a 1: 1 mixed solvent of water and ethanol (ethanol amount 50%), the best yield was obtained, followed by 3: 1 mixing. High yields were obtained when using a solvent (ethanol content 75%). And it turned out that reaction advances with a sufficient yield by making the amount of ethanol in a mixed solvent into 40 to 80%.
（３）パラジウム化合物の担体の検討
実施例１において調製したパラジウム触媒と、その他の担体にパラジウム化合物を担持した触媒を用いて、反応性を比較した。なお、ｐ−ブロモアセトフェノンでは反応が速すぎるため、その代わりにｐ−ブロモアニソールを用いた。
(3) Examination of Palladium Compound Support The reactivity was compared using the palladium catalyst prepared in Example 1 and a catalyst having a palladium compound supported on another support. In addition, since reaction is too quick in p-bromoacetophenone, p-bromoanisole was used instead.
ｐ−ブロモアニソールに対して、それぞれ、１．４当量のフェニルボロン酸、０．０５当量の触媒、２．０当量の炭酸カリウムを用い、これらを水、エタノールの１：１の混合溶媒中で混合し、室温で撹拌して反応を進行させた。結果は表５に示すとおりであり、担体はシリカゲルよりもアルミナ、さらにイオン液体を用いてパラジウム化合物を固定化した場合によい結果が得られた。 For p-bromoanisole, 1.4 equivalents of phenylboronic acid, 0.05 equivalents of catalyst and 2.0 equivalents of potassium carbonate were used, respectively, in a 1: 1 mixed solvent of water and ethanol. The reaction was allowed to proceed by mixing and stirring at room temperature. The results are as shown in Table 5. Good results were obtained when the palladium compound was immobilized using alumina and further an ionic liquid as the carrier rather than silica gel.
（４）基質一般性の検討
ｐ−ブロモアセトフェノンのアセチル基をほかの置換基Ｒ１に変えたアリルブロマイド、フェニルボロン酸のパラ位に置換基Ｒ２を付加したアリルボロン酸を用いて、基質一般性を検討した。
(4) substrate generality studies p- bromoacetophenone other allyl bromide was changed to the substituents R 1 acetyl group, with a Ariruboron acid added with substituent R 2 in the para position of the phenyl boronic acid substrate generality The sex was examined.
アリルブロマイドに対して、それぞれ、１．４当量のアリルボロン酸、０．０５当量のパラジウム触媒、２．０当量の炭酸カリウムを用い、これらを水、エタノールの１：１の混合溶媒中で混合し、室温で撹拌して反応を進行させた。 For allyl bromide, 1.4 equivalents of allylboronic acid, 0.05 equivalents of palladium catalyst, and 2.0 equivalents of potassium carbonate were used, and these were mixed in a 1: 1 mixed solvent of water and ethanol. The reaction was allowed to proceed with stirring at room temperature.
結果は表６に示すとおりであり、Ｒ１、Ｒ２が電子吸引基、電子供与基のいずれの場合も、収率よく反応が進行した。 The results are as shown in Table 6. The reaction proceeded in good yield when R 1 and R 2 were either an electron withdrawing group or an electron donating group.
（５）パラジウム触媒のリサイクル能の検討
ｐ−ブロモアセトフェノンに対して、それぞれ、１．４当量のフェニルボロン酸、０．０５当量のパラジウム触媒、２．０当量の炭酸カリウムを用い、これらを水、エタノールの１：１の混合溶媒中で混合し、室温で撹拌して反応を進行させ、触媒のリサイクル能を検討した。なお、ここで用いたパラジウム触媒の酢酸パラジウム担持量は、０．０２８ｍｍｏｌ／ｇであった。
(5) Examination of recyclability of palladium catalyst For p-bromoacetophenone, 1.4 equivalents of phenylboronic acid, 0.05 equivalents of palladium catalyst, and 2.0 equivalents of potassium carbonate were used. The mixture was mixed in a 1: 1 mixed solvent of ethanol and stirred at room temperature to advance the reaction, and the recycling ability of the catalyst was examined. The palladium catalyst supported on the palladium catalyst used here was 0.028 mmol / g.
結果は表７に示すとおりであり、触媒は平均収率９５％で５回以上のリサイクル使用が可能であった。 The results are as shown in Table 7. The catalyst could be recycled five times or more with an average yield of 95%.
また、ｐ−ブロモアセトフェノンの反応においては瞬間的に反応が進行し、非常に高い反応性を示すことから、触媒回転効率（ＴＯＮ）を調べた。その結果、ターンオーバー数は2,000,000に達し、極めて性能の高い触媒であることが確認された。 Moreover, in the reaction of p-bromoacetophenone, the reaction proceeds instantaneously and shows very high reactivity, so the catalyst rotation efficiency (TON) was examined. As a result, the turnover number reached 2,000,000, and it was confirmed that the catalyst was extremely high in performance.
［反応例］
実施例２で最適化した条件にて反応を行った。
[Example of reaction]
The reaction was performed under the conditions optimized in Example 2.
５ｍｌフラスコにＫ２ＣＯ３（１３９ｍｇ、１．０１ｍｍｏｌ）、フェニルボロン酸（１０１．３ｍｇ、０．８３ｍｍｏｌ）、ｐ−ブロモアセトフェノン（９８ｍｇ、０．４９ｍｍｏｌ）、エタノール（１．０ｍｌ）、水（１．０ｍｌ）を加え、攪拌により溶媒に溶解させた後、酢酸パラジウムを担持したＮＤＥＡＰ−Ａｌ２Ｏ３（８９６ｍｇ、０．０２５ｍｍｏｌ、５ｍｏｌ％相当）を入れ、１分間攪拌し、酢酸エチルにより生成物を抽出した。分離精製はカラム（塩化メチレン／ｎ−ヘキサン＝３／１０）で行い、目的物を９６ｍｇ得た。収率は１００％であった。 In a 5 ml flask was K 2 CO 3 (139 mg, 1.01 mmol), phenylboronic acid (101.3 mg, 0.83 mmol), p-bromoacetophenone (98 mg, 0.49 mmol), ethanol (1.0 ml), water (1 0.0 ml) and dissolved in a solvent by stirring, and then NDEAP-Al 2 O 3 (896 mg, 0.025 mmol, corresponding to 5 mol%) carrying palladium acetate was added and stirred for 1 minute, and the product was stirred with ethyl acetate. Extracted. Separation and purification were performed with a column (methylene chloride / n-hexane = 3/10) to obtain 96 mg of the desired product. The yield was 100%.
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