JP5700624B2 - Cross coupling catalyst composed of ultrafine transition metal particles and cross coupling method using the same - Google Patents
Cross coupling catalyst composed of ultrafine transition metal particles and cross coupling method using the same Download PDFInfo
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- JP5700624B2 JP5700624B2 JP2010139638A JP2010139638A JP5700624B2 JP 5700624 B2 JP5700624 B2 JP 5700624B2 JP 2010139638 A JP2010139638 A JP 2010139638A JP 2010139638 A JP2010139638 A JP 2010139638A JP 5700624 B2 JP5700624 B2 JP 5700624B2
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- transition metal
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- 239000003054 catalyst Substances 0.000 title claims description 81
- 238000006880 cross-coupling reaction Methods 0.000 title claims description 57
- 229910052723 transition metal Inorganic materials 0.000 title claims description 50
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- 238000000034 method Methods 0.000 title description 13
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 76
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 239000002904 solvent Substances 0.000 claims description 36
- 150000001875 compounds Chemical class 0.000 claims description 25
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- 239000003960 organic solvent Substances 0.000 claims description 23
- 229910052763 palladium Inorganic materials 0.000 claims description 20
- 125000003107 substituted aryl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 13
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- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- KBLWLMPSVYBVDK-UHFFFAOYSA-N cyclohexyl prop-2-enoate Chemical compound C=CC(=O)OC1CCCCC1 KBLWLMPSVYBVDK-UHFFFAOYSA-N 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003759 ester based solvent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000004615 furo[2,3-b]pyridinyl group Chemical group O1C(=CC=2C1=NC=CC2)* 0.000 description 1
- 125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 description 1
- 125000004614 furo[3,1-b]pyridinyl group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000005453 ketone based solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004589 thienofuryl group Chemical group O1C(=CC2=C1C=CS2)* 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000004587 thienothienyl group Chemical group S1C(=CC2=C1C=CS2)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229910021381 transition metal chloride Inorganic materials 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Images
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
本発明は、遷移金属超微粒子からなるクロスカップリング用触媒およびそれを用いたクロスカップリング法に関する。具体的には、第８族から第１１族遷移金属から選ばれる少なくとも１つの遷移金属および配位性有機溶媒を含有する遷移金属超微粒子を含むクロスカップリング用触媒、およびそれを用いた高触媒活性なクロスカップリング法に関する。 The present invention relates to a cross-coupling catalyst comprising ultrafine transition metal particles and a cross-coupling method using the same. Specifically, a cross-coupling catalyst comprising ultrafine transition metal particles containing at least one transition metal selected from Group 8 to Group 11 transition metals and a coordinating organic solvent, and a high catalyst using the same The present invention relates to an active cross-coupling method.
現在、プラスチック、医薬品、農薬等において、現代社会において大量の化学物質が消費されており、これらの物質を製造するために触媒を用いた新規製造法を開発することは、効率的な資源・エネルギーの利用並びに地球環境保全という観点から極めて重要である。 Currently, large amounts of chemical substances are consumed in modern society in plastics, pharmaceuticals, agricultural chemicals, etc., and developing new production methods using catalysts to produce these substances is an efficient resource and energy. It is extremely important from the viewpoint of utilization of the environment and global environmental conservation.
とりわけ、炭素−炭素結合生成を伴う異種分子間のクロスカップリング反応は最も重要な触媒反応プロセスとして種々の有機化合物の合成に用いられている。 In particular, the cross-coupling reaction between different kinds of molecules accompanied by carbon-carbon bond formation is used for the synthesis of various organic compounds as the most important catalytic reaction process.
しかしながら、触媒的クロスカップリング反応は学術的には著しい発展を遂げているとはいえ、触媒である貴金属を相当量用いる必要があるため、その多くは工業化には至っていないのが現状である。このため、希少金属資源の有効利用の観点からも、ごく微量の金属触媒を用いた長寿命且つ高活性な触媒反応プロセスの開発が強く望まれている。 However, although the catalytic cross-coupling reaction has made remarkable progress academically, it is necessary to use a considerable amount of a noble metal as a catalyst, and many of them have not yet been industrialized. For this reason, also from the viewpoint of effective utilization of rare metal resources, development of a long-life and high-activity catalytic reaction process using a very small amount of metal catalyst is strongly desired.
近年、金属単体の微粒子化（ナノ粒子化）によって金属の表面露出原子の割合を向上させることにより触媒活性を向上させようとする試みがなされている。しかしながら、通常それら金属粒子は溶液中で互いに凝集し、バルク化するため、触媒本来の活性が損なわれている。 In recent years, attempts have been made to improve the catalytic activity by increasing the ratio of the surface exposed atoms of the metal by making the metal simple particles (nanoparticles). However, since these metal particles usually aggregate with each other in a solution and are bulked, the original activity of the catalyst is impaired.
金属粒子のバルク化の防止によるナノサイズ化のための従来技術としては、配位子（例えば、ピンサー型リン配位子）による安定化（非特許文献１および２）、デンドリマー等の高分子化合物による保護（非特許文献３−５）、ポリマー担持（非特許文献６−１０）、またはイオン性保護剤による保護（非特許文献１１−１２）等が報告されている。しかしながら、そのように従来の金属微粒子は、その合成の過程で配位子または保護剤を使用したり、あるいはポリマー等に担持する等の安定化が必要であった。 Conventional techniques for nano-sizing by preventing bulk formation of metal particles include stabilization by a ligand (for example, pincer-type phosphorus ligand) (Non-patent Documents 1 and 2), polymer compounds such as dendrimers (Non-Patent Documents 3-5), polymer support (Non-Patent Documents 6-10), or protection with an ionic protective agent (Non-Patent Documents 11-12) are reported. However, the conventional fine metal particles need to be stabilized, for example, using a ligand or a protective agent in the process of synthesis, or supporting them on a polymer or the like.
最近、金属塩化物等をジメチルホルムアミド（ＤＭＦ）中で還元することにより、約２ｎｍ以下のナノサイズを有する金、白金、パラジウム等のナノ粒子蛍光体を簡便に且つ大量に合成することができることが報告されている（特許文献１、並びに非特許文献１３−１４を参照）。これらナノ粒子の製造は上述のような配位子または保護剤の使用、あるいはポリマー等への担持の必要がなく、また得られるナノ粒子は安定で粒子径が揃っている。更に、当該ナノ粒子は予想外に、別途の表面処理を施すことなく各種媒体への分散性が高く、媒体中で均一に分散して存在可能である。 Recently, by reducing metal chlorides and the like in dimethylformamide (DMF), it is possible to synthesize nanoparticle phosphors such as gold, platinum and palladium having nanosizes of about 2 nm or less easily and in large quantities. It has been reported (see Patent Literature 1 and Non-Patent Literature 13-14). The production of these nanoparticles does not require the use of a ligand or a protective agent as described above, or support on a polymer or the like, and the obtained nanoparticles are stable and have a uniform particle size. Furthermore, the nanoparticles are unexpectedly highly dispersible in various media without being subjected to a separate surface treatment, and can be uniformly dispersed in the media.
従来のパラジウム錯体をはじめとした触媒的クロスカップリング反応においては、以下にあげる問題点が挙げられ、工業化プロセスとしての観点からは多くの改善すべき課題が残っている。ｉ）使用する触媒量が比較的多い（学術的には１〜５ｍｏｌ％の触媒量で行われている報告例が多い）；ｉｉ）金属触媒の失活を防ぐため、リン化合物等からなる配位子を用い安定化させている；ｉｉｉ）金属触媒の凝集による触媒失活を防ぐため、保護剤で安定化、あるいはシリカ、有機ポリマー等に金属を担持させなければいけない。 In the conventional catalytic cross-coupling reaction including a palladium complex, there are the following problems, and many problems to be improved remain from the viewpoint of industrialization process. i) A relatively large amount of catalyst is used (in many reports, it is academically conducted with a catalyst amount of 1 to 5 mol%); ii) In order to prevent deactivation of the metal catalyst, a catalyst comprising a phosphorus compound or the like It is stabilized using a ligand; iii) In order to prevent catalyst deactivation due to aggregation of the metal catalyst, it must be stabilized with a protective agent, or a metal must be supported on silica, an organic polymer or the like.
本発明は、配位子、保護剤又はポリマー等の構成要素を含まない、遷移金属および配位性有機溶媒からなる遷移金属超微粒子を用いることによって、クロスカップリング反応において触媒上の金属表面を効率的且つ最大限に利用でき、従来の触媒に比べて触媒活性が飛躍的に向上したクロスカップリング反応用触媒、および当該触媒を用いたクロスカップリング反応を提供することを目的とする。 The present invention uses a transition metal ultrafine particle composed of a transition metal and a coordinating organic solvent, which does not contain a component such as a ligand, a protective agent, or a polymer, so that the metal surface on the catalyst is cross-linked. An object of the present invention is to provide a cross-coupling reaction catalyst that can be used efficiently and maximally and has a catalytic activity significantly improved as compared with conventional catalysts, and a cross-coupling reaction using the catalyst.
本発明者が鋭意研究した結果、特願２００９−１５４９３２で得られたナノ粒子をクロスカップリング反応に用いたところ、本発明の遷移金属超微粒子触媒は配位子および保護剤を含まない金属種を用いることができることによって、クロスカップリング反応において触媒上の金属表面を効率的且つ最大限に利用でき、従来の反応系と比べて触媒活性を飛躍的に向上させることが可能となることを見出した。特に、反応基質としてハロアレーンと電子吸引性基を有するオレフィンとを用いる溝呂木−ヘック(Heck)反応、およびハロアレーンと有機ボロン酸とを用いる鈴木−宮浦反応を行ったところ、これらのクロスカップリング反応が良好な収率および高い触媒回転数で効率良く進行することを見出した。すなわち、本発明は以下の通りである。 As a result of intensive studies by the present inventors, when the nanoparticles obtained in Japanese Patent Application No. 2009-154932 were used for the cross-coupling reaction, the transition metal ultrafine particle catalyst of the present invention was a metal species that did not contain a ligand and a protective agent. It is found that the metal surface on the catalyst can be used efficiently and maximally in the cross-coupling reaction, and the catalytic activity can be dramatically improved as compared with the conventional reaction system. It was. In particular, the Mizorogi-Heck reaction using haloarenes and olefins having electron-withdrawing groups as reaction substrates, and the Suzuki-Miyaura reaction using haloarenes and organic boronic acids were performed. It has been found that the process proceeds efficiently with a good yield and a high catalyst rotation speed. That is, the present invention is as follows.
［１］ 第８族から第１１族遷移金属からなる群から選ばれる少なくとも１つの遷移金属および配位性有機溶媒を含有する遷移金属超微粒子を含む、クロスカップリング反応用触媒。 [1] A catalyst for cross-coupling reaction comprising transition metal ultrafine particles containing at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals and a coordinating organic solvent.
［２］ 式：Ａ−Ｘ
（式中、
Ａは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、または無置換もしくは置換のアルケニル基であり；そして、
Ｘは、ハロゲン、メシレート基、トシレート基、トリフラート基、またはカルボン酸ハロゲン化物基である）
で示される化合物と、
式：Ｂ−Ｙ
（式中、
Ｂは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、無置換もしくは置換のアルケニル基、または無置換もしくは置換のアルキニル基であり；
Ｙは、水素、アリール基、アルコキシカルボニル基、ニトロ基、ホルミル基、オキソ基、シアノ基、アミノ基、Ｂ(ＯＲ１)２、ＺｎＸ１、ＡｌＲ２ ２、ＳｎＲ３ ３、ＭｇＸ２、またはＳｉＲ４ ３であり、ここで、Ｘ１およびＸ２はハロゲンであり、そしてＲ１、Ｒ２、Ｒ３およびＲ４は各々独立して水素またはアルキルである）
で示される化合物とを反応させることにより、
式：Ａ−Ｂ
（式中、ＡおよびＢは前掲する通りである）
で示される生成物を得るクロスカップリング反応用である、［１］記載のクロスカップリング反応用触媒。
[2] Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR 1 ) 2 , ZnX 1 , AlR 2 2 , SnR 3 3 , MgX 2 , or SiR 4 3, wherein, X 1 and X 2 is halogen and R 1, R 2, R 3 and R 4 are each independently hydrogen or alkyl)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for cross-coupling reactions according to [1], which is used for a cross-coupling reaction to obtain a product represented by
［３］ 式：Ａ−Ｘ
（式中、
Ａは、無置換もしくは置換のアリール基または無置換もしくは置換のヘテロアリール基であり；そして、
Ｘは、ハロゲン、メシレート基、トシレート基、またはトリフラート基である）
で示される化合物と、
式：Ｂ−Ｙ
（式中、
Ｂは、無置換もしくは置換のアルケニル基または無置換もしくは置換のアリール基であり；
Ｙは、アルコキシカルボニル基またはＢ(ＯＲ１)２であり、そしてＲ１は水素である）
で示される化合物とを反応させることにより、
式：Ａ−Ｂ
（式中、ＡおよびＢは前掲する通りである）
で示される生成物を得るクロスカップリング反応用である、［１］または［２］のいずれか記載のクロスカップリング反応用触媒。
[3] Formula: AX
(Where
A is an unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group; and
X is a halogen, a mesylate group, a tosylate group, or a triflate group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted alkenyl group or an unsubstituted or substituted aryl group;
Y is an alkoxycarbonyl group or B (OR 1 ) 2 and R 1 is hydrogen)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for a cross coupling reaction according to any one of [1] or [2], which is used for a cross coupling reaction to obtain a product represented by:
［４］ 遷移金属が第１０族遷移金属である、［１］乃至［３］のいずれか１項記載のクロスカップリング反応用触媒。 [4] The catalyst for cross-coupling reaction according to any one of [1] to [3], wherein the transition metal is a Group 10 transition metal.
［５］ 遷移金属がパラジウムである、［１］乃至［４］のいずれか１項記載のクロスカップリング反応用触媒。 [5] The catalyst for cross coupling reaction according to any one of [1] to [4], wherein the transition metal is palladium.
［６］ 配位性有機溶媒が、Ｎ,Ｎ−ジメチルホルムアミド（ＤＭＦ）、Ｎ−メチルホルムアミド、Ｎ,Ｎ−ジメチルアセトアミド（ＤＭＡ）、Ｎ−メチルアセトアミド、１,３−ジメチル−２−イミダゾリジノン（ＤＭＩ）、Ｎ−メチル−２−ピロリドン（ＮＭＰ）、およびヘキサメチルホスホリックトリアミド（ＨＭＰＡ）からなる群から選ばれるアミド系溶媒である、［１］乃至［５］のいずれか１項記載のクロスカップリング反応用触媒。 [6] The coordinating organic solvent is N, N-dimethylformamide (DMF), N-methylformamide, N, N-dimethylacetamide (DMA), N-methylacetamide, 1,3-dimethyl-2-imidazolide. Any one of [1] to [5], which is an amide solvent selected from the group consisting of non- (DMI), N-methyl-2-pyrrolidone (NMP), and hexamethylphosphoric triamide (HMPA) The catalyst for cross-coupling reaction as described.
［７］ 配位性有機溶媒がＮ,Ｎ−ジメチルホルムアミド（ＤＭＦ）である、［１］乃至［６］のいずれか１項記載のクロスカップリング反応用触媒。 [7] The catalyst for cross coupling reaction according to any one of [1] to [6], wherein the coordinating organic solvent is N, N-dimethylformamide (DMF).
［８］ 遷移金属超微粒子の平均粒子径が２ｎｍ以下である、［１］乃至［７］のいずれか１項記載のクロスカップリング反応用触媒。 [8] The catalyst for cross-coupling reaction according to any one of [1] to [7], wherein the transition metal ultrafine particles have an average particle size of 2 nm or less.
［９］ 遷移金属超微粒子が蛍光体である、［１］乃至［８］のいずれか１項記載のクロスカップリング反応用触媒。 [9] The catalyst for cross-coupling reaction according to any one of [1] to [8], wherein the transition metal ultrafine particles are phosphors.
［１０］ ターンオーバー数（ＴＯＮ）が１．０×１０４以上を示す、［１］乃至［９］のいずれか１項記載のクロスカップリング反応用触媒。 [10] The catalyst for cross coupling reaction according to any one of [1] to [9], wherein the turnover number (TON) is 1.0 × 10 4 or more.
［１１］ 第８族から第１１族遷移金属からなる群から選ばれる少なくとも１つの遷移金属の塩化物を配位性有機溶媒中で加熱還流することによって調製する、［１］乃至［１０］のいずれか１項記載のクロスカップリング反応用触媒の製造法。 [11] Prepared by heating and refluxing at least one transition metal chloride selected from the group consisting of Group 8 to Group 11 transition metals in a coordinating organic solvent. The manufacturing method of the catalyst for cross coupling reactions of any one of Claims 1.
［１２］ マイクロ波を照射しながら前記加熱還流を行う、［１１］記載の製造法。 [12] The production method according to [11], wherein the heating and refluxing is performed while irradiating microwaves.
［１３］ 前記加熱還流後の反応溶液を適宜溶媒留去し、次いで配位性有機溶媒で希釈して所望の濃度にまで調製する、［１１］または［１２］のいずれか記載の製造法。 [13] The production method according to any one of [11] and [12], wherein the reaction solution after the reflux with heating is appropriately evaporated, and then diluted with a coordinating organic solvent to prepare a desired concentration.
［１４］ ＤＭＦ、ＮＭＰおよびＴＨＦからなる群から選ばれる配位性有機溶媒を用いて希釈する、［１３］記載の製造法。 [14] The production method according to [13], wherein dilution is performed using a coordinating organic solvent selected from the group consisting of DMF, NMP, and THF.
［１５］ 式：Ａ−Ｘ
（式中、
Ａは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、または無置換もしくは置換のアルケニル基であり；そして、
Ｘは、ハロゲン、メシレート基、トシレート基、トリフラート基、またはカルボン酸ハロゲン化物基である）
で示される化合物と、
式：Ｂ−Ｙ
（式中、
Ｂは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、無置換もしくは置換のアルケニル基、または無置換もしくは置換のアルキニル基であり；
Ｙは、水素、アリール基、アルコキシカルボニル基、ニトロ基、ホルミル基、オキソ基、シアノ基、アミノ基、Ｂ(ＯＲ１)２、ＺｎＸ１、ＡｌＲ２ ２、ＳｎＲ３ ３、ＭｇＸ２、またはＳｉＲ４ ３であり、ここで、Ｘ１およびＸ２はハロゲンであり、そしてＲ１、Ｒ２、Ｒ３およびＲ４は各々独立して水素またはアルキルである）
で示される化合物とを、第８族から第１１族遷移金属からなる群から選ばれる少なくとも１つの遷移金属および配位性有機溶媒を含有する遷移金属超微粒子を含む触媒の存在下で反応させることにより、式：Ａ−Ｂ
（式中、ＡおよびＢは前掲する通りである）
で示される生成物を得ることを含む、クロスカップリング反応。
[15] Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR 1 ) 2 , ZnX 1 , AlR 2 2 , SnR 3 3 , MgX 2 , or SiR 4 3, wherein, X 1 and X 2 is halogen and R 1, R 2, R 3 and R 4 are each independently hydrogen or alkyl)
In the presence of a catalyst containing ultrafine transition metal particles containing at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals and a coordinating organic solvent. According to the formula: AB
(In the formula, A and B are as described above.)
A cross-coupling reaction comprising obtaining a product represented by
［１６］ 適宜塩基の存在下で行なう、［１５］記載のクロスカップリング反応。 [16] The cross-coupling reaction according to [15], which is appropriately performed in the presence of a base.
［１７］ 反応溶媒が、配位性有機溶媒の単独または水との混合物である、［１５］または［１６］のいずれか記載のクロスカップリング反応。 [17] The cross-coupling reaction according to any one of [15] or [16], wherein the reaction solvent is a coordination organic solvent alone or a mixture with water.
［１８］ 触媒の使用量が、Ａ−Ｘで示される化合物の配合量基準で１０−１〜１０−７モル％である、［１５］乃至［１７］のいずれか１項記載のクロスカップリング反応。 [18] The cross coupling according to any one of [15] to [17], wherein the amount of the catalyst used is 10 −1 to 10 −7 mol% based on the amount of the compound represented by AX. reaction.
本発明の遷移金属超微粒子は、触媒上の金属表面を効率的且つ最大限に利用でき、従来のクロスカップリング反応系と比べて触媒活性を飛躍的に向上させることができる。 The transition metal ultrafine particles of the present invention can efficiently and maximize the use of the metal surface on the catalyst, and can dramatically improve the catalytic activity as compared with the conventional cross-coupling reaction system.
以下に、本発明をさらに詳細に説明する。
（定義）
以下に、本明細書および特許請求の範囲中で使用する用語の定義を示す。特に断らなければ、本明細書中の基または用語について示す最初の定義を、個別にまたは別の基の一部として本明細書中の基または用語に適用する。
The present invention is described in further detail below.
(Definition)
The definitions of terms used in the present specification and claims are shown below. Unless otherwise indicated, the first definition given for a group or term herein applies to the group or term herein individually or as part of another group.
用語「第８族から第１１族遷移金属からなる群から選ばれる少なくとも１つの遷移金属」とは、第８族遷移金属（例えば、鉄（Ｆｅ）、ルテニウム（Ｒｕ）、オスミウム（Ｏｓ））、第９族遷移金属（例えば、コバルト（Ｃｏ）、ロジウム（Ｒｈ）、イリジウム（Ｉｒ））、第１０族遷移金属（例えば、ニッケル（Ｎｉ）、パラジウム（Ｐｄ）、白金（Ｐｔ））、および第１１族遷移金属（例えば、銅（Ｃｕ）、銀（Ａｇ）、金（Ａｕ））からなる群から選ばれる少なくとも１つの遷移金属を意味する。第１０族遷移金属が好ましく、白金、パラジウムがより好ましく、パラジウムが特に好ましい。 The term “at least one transition metal selected from the group consisting of Group 8 to Group 11 transition metals” refers to Group 8 transition metals (eg, iron (Fe), ruthenium (Ru), osmium (Os)), Group 9 transition metals (eg, cobalt (Co), rhodium (Rh), iridium (Ir)), Group 10 transition metals (eg, nickel (Ni), palladium (Pd), platinum (Pt)), and It means at least one transition metal selected from the group consisting of group 11 transition metals (for example, copper (Cu), silver (Ag), gold (Au)). Group 10 transition metals are preferred, platinum and palladium are more preferred, and palladium is particularly preferred.
用語「配位性有機溶媒」とは、遷移金属と配位することが可能な有機溶媒を意味し、例えば、アミド系溶媒、アミン系溶媒、アルコール系溶媒、エーテル系溶媒、ケトン系溶媒、エステル系溶媒、ニトリル系溶媒、ニトロ系溶媒、もしくはスルホキシド系溶媒、またはそれらの２種以上の混合溶媒を含む。具体的には例えば、Ｎ,Ｎ−ジメチルホルムアミド（ＤＭＦ）、Ｎ,Ｎ−ジメチルアセトアミド（ＤＭＡ）、１,３−ジメチル−２−イミダゾリジノン（ＤＭＩ）、Ｎ−メチル−２−ピロリドン（ＮＭＰ）等のカルボン酸アミド系、ヘキサメチルホスホリックトリアミド（ＨＭＰＡ）等のリン酸アミド系を含むアミド系溶媒；トリエチルアミン、ピリジン、エタノールアミン等のアミン系溶媒；イソプロパノール、プロピレングリコール等のアルコール系溶媒；ジエチルエーテル、ジイソプロピルエーテル、ジオキサン、テトラヒドロフラン（ＴＨＦ）等のエーテル系溶媒；アセトン、２−ブタノン等のケトン系溶媒；酢酸エチル、酢酸メチル等のエステル系溶媒；アセトニトリル等のニトリル系溶媒；ニトロメタン等のニトロ系溶媒；ジメチルスルホキシド等のスルホキシド系溶媒を挙げられる。ＤＭＦ、Ｎ−メチルホルムアミド、ＤＭＡ、Ｎ−メチルアセトアミド、ＤＭＩ、ＮＭＰ、ＨＭＰＡからなる群から選ばれるアミド系溶媒が好ましく、ＤＭＦが特に好ましい。 The term “coordinating organic solvent” means an organic solvent capable of coordinating with a transition metal, such as an amide solvent, an amine solvent, an alcohol solvent, an ether solvent, a ketone solvent, and an ester. A system solvent, a nitrile solvent, a nitro solvent, or a sulfoxide solvent, or a mixed solvent of two or more thereof. Specifically, for example, N, N-dimethylformamide (DMF), N, N-dimethylacetamide (DMA), 1,3-dimethyl-2-imidazolidinone (DMI), N-methyl-2-pyrrolidone (NMP) ) Amide solvents including carboxylic acid amides such as hexamethylphosphoric triamide (HMPA); amine solvents such as triethylamine, pyridine and ethanolamine; alcohol solvents such as isopropanol and propylene glycol Ether solvents such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran (THF); ketone solvents such as acetone and 2-butanone; ester solvents such as ethyl acetate and methyl acetate; nitrile solvents such as acetonitrile; nitromethane and the like Nitro solvents of dimethyl It includes a sulfoxide-based solvents such as sulfoxide. Amide solvents selected from the group consisting of DMF, N-methylformamide, DMA, N-methylacetamide, DMI, NMP, and HMPA are preferred, and DMF is particularly preferred.
用語「遷移金属超微粒子」とは、上記第８族から第１１族遷移金属からなる群から選ばれる少なくとも１つの遷移金属および配位性有機溶媒を含有する溶媒保護化物であって、その平均粒子径がナノサイズの粒子を意味する。ここで、溶媒保護化物とは、それら配位性溶媒で保護された化合物を意味する。また、本願明細書中、「超微粒子」は「ナノ粒子」または「ＮＣｓ」とも呼称される。 The term “transition metal ultrafine particles” is a solvent-protected product containing at least one transition metal selected from the group consisting of the above Group 8 to Group 11 transition metals and a coordinating organic solvent, and its average particle A particle having a diameter of nano size is meant. Here, the solvent-protected product means a compound protected with these coordinating solvents. In the present specification, “ultrafine particles” are also referred to as “nanoparticles” or “NCs”.
平均粒子径は０．５〜４ｎｍ程度であって、２ｎｍ以下が好ましく、１．５ｎｍ程度がより好ましい。かかる粒子径は、透過型電子顕微鏡（ＴＥＭ）の像の解析により確認する。例えば、パラジウム超微粒子および白金超微粒子の各ＴＥＭの像を示す（図１）。図１より、パラジウム超微粒子および白金超微粒子はそれぞれ平均粒子径が約１．５ｎｍである。また、特願２００９−１５４９３２に記載する通りパラジウム、白金以外の遷移金属超微粒子についても蛍光特性を示すことから、平均粒子径は２ｎｍ以下である。また、かかる蛍光特性と２ｎｍ以下の平均粒子径との相関関係については、以下の多数の文献中に記載されている：
1. S. Empedocles, M. Baewndi著, Acc. Chem. Res, 1999, 32, 389-396.
2. M. A. El-Sayed著, Acc. Chem. Res, 2001, 34, 257-264.
3. S. Link, M. A. El-Sayed著, Int. Rev. Phys. Chem. 200, 19, 409-453.
4. S. Link, A. Beeby, S. FitzGerald, M. A. El-Sayed, T. G. Schaaff, R. L.
Whetten著, J. Phys. Chem. B, 2002, 106, 3410-3415,
5. S. Chen, R. S. Ingram, M. J. Hostetler, J. J. Pietron, R. W. Murrey, T. G. Schaaff, J. T. Khoury, M. M. Alvarez, R. L. Whetten著, Science, 1998, 280, 2098-2101.
The average particle size is about 0.5 to 4 nm, preferably 2 nm or less, and more preferably about 1.5 nm. The particle diameter is confirmed by analyzing a transmission electron microscope (TEM) image. For example, TEM images of palladium ultrafine particles and platinum ultrafine particles are shown (FIG. 1). From FIG. 1, the palladium ultrafine particles and the platinum ultrafine particles each have an average particle diameter of about 1.5 nm. In addition, as described in Japanese Patent Application No. 2009-154932, since transition metal ultrafine particles other than palladium and platinum also exhibit fluorescence characteristics, the average particle diameter is 2 nm or less. Also, the correlation between such fluorescence properties and an average particle size of 2 nm or less is described in a number of documents:
1. S. Empedocles, M. Baewndi, Acc. Chem. Res, 1999, 32, 389-396.
2. MA El-Sayed, Acc. Chem. Res, 2001, 34, 257-264.
3. S. Link, MA El-Sayed, Int. Rev. Phys. Chem. 200, 19, 409-453.
4. S. Link, A. Beeby, S. FitzGerald, MA El-Sayed, TG Schaaff, RL
Whetten, J. Phys. Chem. B, 2002, 106, 3410-3415,
5. S. Chen, RS Ingram, MJ Hostetler, JJ Pietron, RW Murrey, TG Schaaff, JT Khoury, MM Alvarez, RL Whetten, Science, 1998, 280, 2098-2101.
用語「クロスカップリング反応」とは、異なる２種の化合物の間で選択的に結合する反応を意味する。特に、本発明で意図するクロスカップリング反応とは、遷移金属化合物が触媒的に作用する、下式：
用語「式：Ａ−Ｘで示される化合物」とは、上記クロスカップリング反応において求電子剤として作用する反応基質の一方を意味する。ここで、基Ａは、少なくとも１つの炭素−炭素不飽和結合を有する基であり、具体的には、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、および無置換もしくは置換のアルケニル基を含む。無置換もしくは置換のアリール基または無置換もしくは置換のヘテロアリール基が好ましい。また、Ｘ基は有機化学分野において脱離基として知られる基を意味する。具体的には、ハロゲン（例えば、クロロ、ブロモ、ヨード）、メシレート基（ＯＭｓ）、トシレート基（ＯＴｓ）、またはカルボン酸ハロゲン化物基（例えば、カルボン酸臭化物（Ｃ(＝Ｏ)Ｂｒ、カルボン酸ヨウ化物（Ｃ(＝Ｏ)Ｉ））を挙げられる。ハロゲンが好ましく、ブロモまたはヨードがより好ましく、ヨードが特に好ましい。 The term “compound represented by the formula: AX” means one of the reaction substrates that acts as an electrophile in the cross-coupling reaction. Here, the group A is a group having at least one carbon-carbon unsaturated bond, specifically, an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, and an unsubstituted or substituted group. Contains an alkenyl group. An unsubstituted or substituted aryl group or an unsubstituted or substituted heteroaryl group is preferred. The X group means a group known as a leaving group in the field of organic chemistry. Specifically, halogen (for example, chloro, bromo, iodo), mesylate group (OMs), tosylate group (OTs), or carboxylic acid halide group (for example, carboxylic acid bromide (C (= O) Br, carboxylic acid) Iodide (C (= O) I)), halogen is preferred, bromo or iodo is more preferred, and iodo is particularly preferred.
用語「式：Ｂ−Ｙで示される化合物」とは、上記クロスカップリング反応において求核剤として作用する反応基質の一方を意味する。ここで、基Ｂは、少なくとも１つの炭素−炭素不飽和結合を有する基であり、具体的には、無置換もしくは置換のアリール、無置換もしくは置換のヘテロアリール基、無置換もしくは置換のアルケニル基、および無置換もしくは置換のアルキニル基を含む。無置換もしくは置換のアルケニル基または無置換もしくは置換のアリール基が好ましい。また、Ｙ基は、水素、アリール基、アルコキシカルボニル基、ニトロ基、ホルミル基、オキソ基、シアノ基、アミノ基、Ｂ(ＯＲ１)２、ＺｎＸ１、ＡｌＲ２ ２、ＳｎＲ３ ３、ＭｇＸ２、またはＳｉＲ４ ３であり、ここで、Ｘ１およびＸ２はハロゲン（クロロ、ブロモ、ヨードが好ましく、ブロモ、ヨードがより好ましい）であり、そしてＲ１、Ｒ２、Ｒ３およびＲ４は各々独立して水素またはアルキル（炭素数が１〜６のアルキルが好ましく、メチル、エチル、ｔ−ブチルがより好ましい）である。アルコキシカルボニル基（例えば、エトキシカルボニル）、またはＢ(ＯＲ１)２（Ｒ１は水素である）が好ましい。 The term “compound represented by the formula: BY” means one of the reaction substrates that acts as a nucleophile in the cross-coupling reaction. Here, the group B is a group having at least one carbon-carbon unsaturated bond, specifically, an unsubstituted or substituted aryl, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group. And unsubstituted or substituted alkynyl groups. An unsubstituted or substituted alkenyl group or an unsubstituted or substituted aryl group is preferred. Y group is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR 1 ) 2 , ZnX 1 , AlR 2 2 , SnR 3 3 , MgX 2. Or SiR 4 3 where X 1 and X 2 are halogens (chloro, bromo, iodo are preferred, bromo, iodo are more preferred) and R 1 , R 2 , R 3 and R 4 are Each is independently hydrogen or alkyl (C1-C6 alkyl is preferable, and methyl, ethyl, and t-butyl are more preferable). An alkoxycarbonyl group (eg ethoxycarbonyl) or B (OR 1 ) 2 (R 1 is hydrogen) is preferred.
用語「無置換もしくは置換のアリール基」とは、適宜１〜５個の置換基を有する芳香族性炭素環式を意味する。縮合環様式で結合した多環式基（例えば、二環式基）をも本定義に含む。具体例としては、フェニル基、１−ナフチル基、２−ナフチル基等の単環式アリール基；フェナントリジニル基、６−クロマニル基、５−イソインドリル基等の二環式アリール基等が挙げられる。フェニル基、１−ナフチル基、２−ナフチル基が好ましい。 The term “unsubstituted or substituted aryl group” means an aromatic carbocyclic group having 1 to 5 substituents as appropriate. Also included in this definition are polycyclic groups (eg, bicyclic groups) linked in a fused ring fashion. Specific examples include monocyclic aryl groups such as phenyl group, 1-naphthyl group and 2-naphthyl group; bicyclic aryl groups such as phenanthridinyl group, 6-chromanyl group and 5-isoindolyl group. It is done. A phenyl group, a 1-naphthyl group, and a 2-naphthyl group are preferable.
ここで、置換基としては、かかるクロスカップリング反応の進行を妨げない基であればよく、有機化学分野において知られる電子供与性基（例えば、アミノ基、アルキル基、アルコキシ基）または電子吸引性基（例えば、ニトロ基、ホルミル基、オキソ基、シアノ基、アルコキシカルボニル基）のいずれであってもよいが、電子供与性基が好ましい。例えば、アルキル基（例えば、炭素数が１〜６個のアルキル基（例えば、メチル基、エチル基））、ハロゲン化アルキル基（例えば、トリフルオロメチル基）、ニトロ基、ホルミル基、オキソ基、アシル基（例えば、アセチル基、プロピオニル基、ブチリル基）、アミノ基（例えば、N-メチルアミノ基、N-エチルアミノ基、N,N-ジメチルアミノ基、N,N-ジフェニルアミノ基）、ヒドロキシ基、アルコキシ基（例えば、メトキシ基、エトキシ基）、カルボキシ基、シアノ基を含む。アルキル基、ハロゲン化アルキル基、アルコキシ基が好ましい。 Here, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and is known as an electron donating group (for example, amino group, alkyl group, alkoxy group) or electron withdrawing property known in the field of organic chemistry. Any of groups (for example, nitro group, formyl group, oxo group, cyano group, alkoxycarbonyl group) may be used, but an electron donating group is preferable. For example, an alkyl group (for example, an alkyl group having 1 to 6 carbon atoms (for example, a methyl group, an ethyl group)), a halogenated alkyl group (for example, a trifluoromethyl group), a nitro group, a formyl group, an oxo group, Acyl group (eg, acetyl group, propionyl group, butyryl group), amino group (eg, N-methylamino group, N-ethylamino group, N, N-dimethylamino group, N, N-diphenylamino group), hydroxy Group, alkoxy group (for example, methoxy group, ethoxy group), carboxy group, and cyano group. Alkyl groups, halogenated alkyl groups, and alkoxy groups are preferred.
用語「無置換もしくは置換のヘテロアリール基」とは、適宜１〜５個の置換基を有する、少なくとも１つの環内に、窒素原子、酸素原子、または硫黄原子から選ばれる少なくとも１つのヘテロ原子を有する、芳香族性の環式基を意味する。縮合環様式で結合した多環式基（例えば、二環式基）をも本定義に含む。具体例としては、ピロリル基、ピラゾリル基、イミダゾリル基、オキサゾリル基、イソキサゾリル基、チアゾリル基、チアジアゾリル基、イソチアゾリル基、ピリジル基、フリル基、チエニル基、オキサジアゾリル基、２−オキサアゼピニル基、アゼピニル基、ピラジニル基、ピリミジニル基、ピリダジニル基、トリアジニル基、トリアゾリル基などの単環式へテロアリール基；および、ベンゾチアゾリル基、ベンゾキサゾリル基、ベンゾチエニル基、ベンゾフリル基、キノリニル基、キノリニル−Ｎ−オキシド基、イソキノリニル基、ベンゾイミダゾリル基、ベンゾピラニル基、インドリジニル基、シンノリニル基、キノキサリニル基、インダゾリル基、ピロロピリジル基、フロピリジニル基（例えば、フロ[２,３−ｃ]ピリジニル基、フロ[３,１−ｂ]ピリジニル基、またはフロ[２,３−ｂ]ピリジニル基）、ベンジイソチアゾリル基、ベンゾイソキサゾリル基、ベンゾジアジニル基、ベンゾチオピラニル基、ベンゾトリアゾリル基、ベンゾピラゾリル基、ナフチリジニル基、フタラジニル基、プリニル基、ピリドピリジル基、キナゾリニル基、チエノフリル基、チエノピリジル基、チエノチエニル基などの二環式ヘテロアリール基等の二環式アリール基等が挙げられる。ピリジル基が好ましい。置換基としては、上記の「無置換もしくは置換のアリール基」において定義するのと同様に、かかるクロスカップリング反応の進行を妨げない基であればよく、具体例は上述の通りである。 The term “unsubstituted or substituted heteroaryl group” refers to at least one heteroatom selected from a nitrogen atom, an oxygen atom, or a sulfur atom in at least one ring having 1 to 5 substituents as appropriate. Means an aromatic cyclic group. Also included in this definition are polycyclic groups (eg, bicyclic groups) linked in a fused ring fashion. Specific examples include pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, pyridyl, furyl, thienyl, oxadiazolyl, 2-oxaazepinyl, azepinyl, pyrazinyl Group, pyrimidinyl group, pyridazinyl group, triazinyl group, triazolyl group and the like monocyclic heteroaryl group; and benzothiazolyl group, benzoxazolyl group, benzothienyl group, benzofuryl group, quinolinyl group, quinolinyl-N-oxide group, isoquinolinyl group, Benzoimidazolyl group, benzopyranyl group, indolizinyl group, cinnolinyl group, quinoxalinyl group, indazolyl group, pyrrolopyridyl group, furopyridinyl group (for example, furo [2,3-c] pyridinyl group, furo [ 3,1-b] pyridinyl group or furo [2,3-b] pyridinyl group), benzisothiazolyl group, benzisoxazolyl group, benzodiazinyl group, benzothiopyranyl group, benzotriazolyl group, And bicyclic aryl groups such as bicyclic heteroaryl groups such as benzopyrazolyl group, naphthyridinyl group, phthalazinyl group, purinyl group, pyridopyridyl group, quinazolinyl group, thienofuryl group, thienopyridyl group, and thienothienyl group. A pyridyl group is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.
用語「無置換もしくは置換のアルケニル基」とは、適宜１〜５個の置換基を有する、２〜１２個の炭素原子および少なくとも１個の二重結合を有する、直鎖、分枝または環状の炭化水素基を意味する。具体例としては、エテニル基（ビニル基）、１−プロペニル基、１−ブテニル基、１−ペンテニル基、１,３−ジペンテニル基、シクロヘキセニル基等を挙げられる。エテニル基が好ましい。置換基としては、上記の「無置換もしくは置換のアリール基」において定義するのと同様に、かかるクロスカップリング反応の進行を妨げない基であればよく、具体例は上述の通りである。 The term “unsubstituted or substituted alkenyl group” means a straight, branched or cyclic group having 2 to 12 carbon atoms and at least one double bond, optionally having 1 to 5 substituents. A hydrocarbon group is meant. Specific examples include ethenyl group (vinyl group), 1-propenyl group, 1-butenyl group, 1-pentenyl group, 1,3-dipentenyl group, cyclohexenyl group and the like. An ethenyl group is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.
用語「無置換もしくは置換のアルキニル基」とは、適宜１〜３個の置換基を有する、２〜６個の炭素原子および１個の三重結合を有する、直鎖または分枝の炭化水素基を意味する。アセチレンの一端の炭素上の水素が水素以外の基で置換された末端アルキニル基が好ましい。具体例としては、１−プロピニル、１−ブチニル、３,３−ジメチル−１−ブチニル等を挙げられる。１−プロピニルが好ましい。置換基としては、上記の「無置換もしくは置換のアリール基」において定義するのと同様に、かかるクロスカップリング反応の進行を妨げない基であればよく、具体例は上述の通りである。 The term “unsubstituted or substituted alkynyl group” refers to a linear or branched hydrocarbon group having 2 to 6 carbon atoms and one triple bond, optionally having 1 to 3 substituents. means. A terminal alkynyl group in which hydrogen on carbon at one end of acetylene is substituted with a group other than hydrogen is preferable. Specific examples include 1-propynyl, 1-butynyl, 3,3-dimethyl-1-butynyl and the like. 1-propynyl is preferred. As defined in the above “unsubstituted or substituted aryl group”, the substituent may be any group that does not hinder the progress of the cross-coupling reaction, and specific examples are as described above.
用語「アルコキシカルボニル基」とは、炭素数が１〜１２個、好ましくは炭素数が１〜８個、より好ましくは炭素数が１〜６個のアルキル基を含むアルコキシカルボニル基を意味する。具体例としては、メトキシカルボニル、エトキシカルボニル、ｎ−プロポキシカルボニル、ブトキシカルボニル（ｎ−ブトキシカルボニル、イソ−ブトキシカルボニル、ｔ−ブトキシカルボニル）、ペンチルオキシカルボニル、ヘキシルオキシカルボニル等を挙げられる。メトキシカルボニル、エトキシカルボニル、ｔ−ブトキシカルボニルが好ましい。 The term “alkoxycarbonyl group” means an alkoxycarbonyl group containing an alkyl group having 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, more preferably 1 to 6 carbon atoms. Specific examples include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, butoxycarbonyl (n-butoxycarbonyl, iso-butoxycarbonyl, t-butoxycarbonyl), pentyloxycarbonyl, hexyloxycarbonyl and the like. Methoxycarbonyl, ethoxycarbonyl and t-butoxycarbonyl are preferred.
本発明の反応を以下に詳しく説明する。
（触媒の調製）
本発明のクロスカップリング反応用触媒は上記反応式１に示す通りに調製する。具体的には、まず特願２００９−１５４９３２中の記載と同様に、第８族−第１１族遷移金属化合物の原料を配位性有機溶媒中で加熱還流することによって反応させ、反応溶液を得る。マイクロ波を照射しながら加熱還流することが好ましい。この反応は、空気雰囲気下で行うことができる。また、反応温度は、通常使用する配位性有機溶媒の沸点近くで行う。更に、反応時間は、使用する溶媒、反応温度などの反応条件に依存して変わり得るが、数時間〜数日間で完結し、通常約４時間〜約１日間で完結し、約６時間が好ましい。
(Preparation of catalyst)
The catalyst for cross-coupling reaction of the present invention is prepared as shown in the above reaction formula 1. Specifically, first, as described in Japanese Patent Application No. 2009-154932, the raw materials of Group 8 to Group 11 transition metal compounds are reacted by heating and refluxing in a coordinating organic solvent to obtain a reaction solution. . It is preferable to heat and reflux while irradiating with microwaves. This reaction can be carried out in an air atmosphere. Moreover, reaction temperature is performed near the boiling point of the coordinating organic solvent used normally. Furthermore, the reaction time may vary depending on the reaction conditions such as the solvent used and the reaction temperature, but it is completed in several hours to several days, usually about 4 hours to about 1 day, and preferably about 6 hours. .
第８族−第１１族遷移金属化合物の原料としては、各遷移金属の無機化合物（例えば、塩化物、硫酸化物、硝酸化物）であってよく、具体的には、Ｐｄの場合にはＰｄＣｌ２、[Ｐｄ(ＮＨ３)４]Ｃｌ２など；Ｐｔの場合にはＨ２ＰｔＣｌ６、[Ｐｔ(ＮＨ３)４]Ｃｌ２等；Ｆｅの場合にはＦｅＣｌ３、Ｆｅ２(ＳＯ４)３等；Ａｕの場合には、ＨＡｕＣｌ４、Ｎａ[Ａｕ(ＣＮ)４]等；Ｃｕの場合には、ＣｕＣｌ２、ＣｕＳＯ４等；Ａｇの場合には、ＡｇＮＯ３、[Ａｇ(ＮＨ３)２]ＮＯ３等を挙げられる。塩化物が好ましい。これらは、市販されているか、または当該有機金属化学の分野において知られる方法、或いはこれらに準じた方法により製造することができる。 The raw material of the Group 8 to Group 11 transition metal compound may be an inorganic compound of each transition metal (for example, chloride, sulfate, or nitrate). Specifically, in the case of Pd, PdCl 2 , [Pd (NH 3 ) 4 ] Cl 2, etc .; in the case of Pt, H 2 PtCl 6 , [Pt (NH 3 ) 4 ] Cl 2, etc .; in the case of Fe, FeCl 3 , Fe 2 (SO 4 ) 3 In the case of Au, HAuCl 4 , Na [Au (CN) 4 ] etc .; in the case of Cu, CuCl 2 , CuSO 4 etc .; in the case of Ag, AgNO 3 , [Ag (NH 3 ) 2 ] NO 3 etc. are mentioned. Chloride is preferred. These are commercially available, or can be produced by a method known in the field of the organometallic chemistry or a method analogous thereto.
次に、得られた反応溶液を、配位性有機溶媒で希釈して所望の濃度へ調整して遷移金属超微粒子触媒を得ることができる。ここで、反応溶媒と希釈溶媒とが相違する場合には、反応溶媒を留去し、その後に希釈を行う。例えば、１ｍＭの反応溶液を得て、これを希釈して１０μＭ、１００ｎＭ、１０ｎＭ、１ｎＭの濃度にまで調製することができる。 Next, the obtained reaction solution can be diluted with a coordinating organic solvent and adjusted to a desired concentration to obtain a transition metal ultrafine particle catalyst. Here, when the reaction solvent and the diluting solvent are different, the reaction solvent is distilled off, followed by dilution. For example, a 1 mM reaction solution can be obtained and diluted to a concentration of 10 μM, 100 nM, 10 nM, 1 nM.
（クロスカップリング反応）
クロスカップリング反応は、上記反応式２に示す通り一般に触媒的クロスカップリング反応として知られる手順に準じて行う。具体的には、式：Ａ−Ｘで示される化合物（１）と、式：Ｂ−Ｙで示される化合物（２）とを、上記で得られた遷移金属超微粒子触媒の存在下で反応させる。ここで、クロスカップリング反応のタイプによっては、塩基の存在下で行う。塩基としては、有機塩基（例えば、トリエチルアミン、ピリジン）または無機塩基（例えば、水酸化物（例えば、水酸化ナトリウム））、炭酸塩（例えば、炭酸カリウム）、炭酸水素塩（例えば、炭酸水素ナトリウム））を挙げられる。
(Cross coupling reaction)
The cross coupling reaction is generally performed according to a procedure known as a catalytic cross coupling reaction as shown in the above reaction formula 2. Specifically, the compound (1) represented by the formula: AX and the compound (2) represented by the formula: BY are reacted in the presence of the transition metal ultrafine particle catalyst obtained above. . Here, depending on the type of the cross-coupling reaction, the reaction is performed in the presence of a base. Bases include organic bases (eg triethylamine, pyridine) or inorganic bases (eg hydroxides (eg sodium hydroxide)), carbonates (eg potassium carbonate), bicarbonates (eg sodium bicarbonate) ).
反応基質である、式：Ａ−Ｘで示される化合物（１）と、式：Ｂ−Ｙで示される化合物（２）はいずれも市販されているか、または当該有機化学の分野において知られる方法、或いはこれらに準じた方法により製造することができる。 A compound (1) represented by the formula: AX and a compound (2) represented by the formula: BY, which are reaction substrates, are either commercially available or a method known in the field of organic chemistry, Or it can manufacture by the method according to these.
クロスカップリング反応の反応溶媒は、配位性有機溶媒の単独または水との混合物を使用することができる。水との混合物を使用する場合には、反応溶媒総量中の配位性有機溶媒の比率が５容量％以上、２０容量％以上、好ましくは５０容量％以上である。配位性反応溶媒としては、ＤＭＦ、ＮＭＰおよびＴＨＦが好ましく、特に溝呂木・ヘック反応の場合にはＤＭＦが、鈴木・宮浦カップリングの場合にはＮＭＰが好ましい。 As a reaction solvent for the cross-coupling reaction, a coordinating organic solvent alone or a mixture with water can be used. When a mixture with water is used, the ratio of the coordinating organic solvent in the total amount of the reaction solvent is 5% by volume or more, 20% by volume or more, preferably 50% by volume or more. As the coordinating reaction solvent, DMF, NMP and THF are preferable. Particularly, in the case of Mizorogi-Heck reaction, DMF is preferable, and in the case of Suzuki-Miyaura coupling, NMP is preferable.
反応基質である化合物（１）と化合物（２）の配合量比率は、化合物（２）の量が化合物（１）の配合量基準で等量または過剰量で使用する。例えば、化合物（２）を、１．０〜３．０当量、１．０〜２．０当量、好ましくは１．２〜１．５当量で使用する。 The compounding ratio of the compound (1) and the compound (2) as the reaction substrate is such that the amount of the compound (2) is equal or excessive based on the compounding amount of the compound (1). For example, the compound (2) is used in an amount of 1.0 to 3.0 equivalents, 1.0 to 2.0 equivalents, preferably 1.2 to 1.5 equivalents.
本発明の遷移金属超微粒子触媒の使用量は、反応基質である化合物（１）の配合量基準で１０−１〜１０−７モル％、１０−２〜１０−７モル％、好ましくは１０−３〜１０−７モル％で使用することができる。特に、溝呂木・ヘック反応の場合には１０−５〜１０−７モル％で、鈴木・宮浦カップリングの場合には１０−３モル％で使用することができる。 The transition metal ultrafine particle catalyst of the present invention is used in an amount of 10 −1 to 10 −7 mol%, 10 −2 to 10 −7 mol%, preferably 10 − based on the amount of compound (1) as the reaction substrate. it can be used in three to 10-7 mol%. In particular, it can be used at 10 −5 to 10 −7 mol% in the case of Mizorogi-Heck reaction, and at 10 −3 mol% in the case of Suzuki-Miyaura coupling.
触媒活性は、触媒化学分野においてよく用いられる触媒回転数（ＴＯＮ）を用いて表すことができる。本発明の触媒は、１０４〜１０８の次数のＴＯＮを示す。例えば、鈴木・宮浦カップリングの場合には、１０４の次数、すなわち最大で万単位のＴＯＮを、溝呂木・ヘック反応の場合には１０４〜１０８の次数、すなわち最大で億単位のＴＯＮを示し得る。 Catalytic activity can be expressed using the catalyst rotational speed (TON) often used in the field of catalytic chemistry. The catalyst of the present invention exhibits a TON of the order of 10 4 to 10 8 . For example, in the case of the Suzuki-Miyaura coupling, an order of 10 4 , that is, a maximum of 10,000 units of TON, and in the case of the Mizorogi-Heck reaction, an order of 10 4 to 10 8 , that is, a maximum of 100 million units of TON. Can show.
本発明のカップリング反応は、低温（例えば、−７０℃以下）から高温（例えば、１００℃以上）で行なうことができ、通常室温〜使用する反応溶媒の沸点であり、８０〜１４０が好ましく、１００℃〜１４０℃がより好ましい。 The coupling reaction of the present invention can be performed at a low temperature (for example, −70 ° C. or lower) to a high temperature (for example, 100 ° C. or higher), and is usually from room temperature to the boiling point of the reaction solvent used, preferably 80 to 140, 100 degreeC-140 degreeC is more preferable.
本発明の反応は、不活性気体の雰囲気下で行なうことが好ましく、具体的には窒素、アルゴン、ヘリウムの雰囲気下で行なう。 The reaction of the present invention is preferably performed in an atmosphere of an inert gas, specifically, in an atmosphere of nitrogen, argon, or helium.
本発明の反応は、常圧から加圧容器（例えば、プレッシャーチューブなどの市販のステンレス加圧容器）中での加圧条件下で行なうことができ、通常常圧で行なう。 The reaction of the present invention can be carried out under normal pressure from a normal pressure in a pressure vessel (for example, a commercially available stainless steel pressure vessel such as a pressure tube), and is usually carried out at normal pressure.
本発明の反応時間は、使用する溶媒、反応温度などの反応条件に依存して変わり得るが、数時間〜数日間で完結し、通常３時間〜２日間で完結し、５時間〜１５時間が好ましい。 The reaction time of the present invention may vary depending on the reaction conditions such as the solvent used and the reaction temperature, but it is completed in several hours to several days, usually 3 hours to 2 days, and 5 hours to 15 hours. preferable.
以下に実施例を挙げて本発明を更に具体的に説明するが、本発明はこれら実施例に限定されるものではない。遷移金属超微粒子およびクロスカップリング反応の生成物の確認は、各種分光学的分析の解析により行なった。具体的には、一次元および二次元のプロトンおよび炭素１３核磁気共鳴スペクトル（１Ｈ ＮＭＲ、１３Ｃ ＮＭＲ、質量スペクトル（ＭＳ）、赤外線吸収スペクトル(ＩＲ）、蛍光スペクトル、透過型電子顕微鏡（ＴＥＭ）の解析により行った。核磁気共鳴スペクトルには、テトラメチルシランを内部標準として用いた。反応収率は、シリカゲルガスクロマトグラフィー（ＧＣ）を用いて定量した。 EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples. The transition metal ultrafine particles and the product of the cross-coupling reaction were confirmed by analysis of various spectroscopic analyses. Specifically, one- and two-dimensional proton and carbon 13 nuclear magnetic resonance spectra ( 1 H NMR, 13 C NMR, mass spectrum (MS), infrared absorption spectrum (IR), fluorescence spectrum, transmission electron microscope (TEM) In the nuclear magnetic resonance spectrum, tetramethylsilane was used as an internal standard, and the reaction yield was quantified using silica gel gas chromatography (GC).
実施例中に用いた以下の略号を説明する。
Ｍｅはメチル基を、Ｅｔはエチル基を、ｔ−Ｂｕはｔ−ブチル基を、Ｃｙをシクロヘキシル基を意味する。
The following abbreviations used in the examples will be described.
Me represents a methyl group, Et represents an ethyl group, t-Bu represents a t-butyl group, and Cy represents a cyclohexyl group.
［参考例］
［遷移金属超微粒子の合成］
１．パラジウム超微粒子の調製
本発明において使用する遷移金属超微粒子は、特願２００９−１５４９３２の記載と同様に調製した。具体的には、三口フラスコに回転子を入れ、DMFで共洗いしたのちに、DMF (15 mL)を入れ、空気雰囲気下、140℃で6分間、三口フラスコを予備加熱した。その後、0.1 Mの塩化パラジウム水溶液を150 μL加え、140℃、6時間加熱環流し合成を行った。パラジウム超微粒子溶液は、1 mMの溶液 (1 mM Pd超微粒子（ナノ粒子）（NCs)／DMF)として得られ、紫外可視吸収スペクトル、蛍光スペクトル、TEMを用いて分析し、約1.5 nmの粒子の生成を確認した（図１（Ａ））。
[Reference example]
[Synthesis of transition metal ultrafine particles]
1. Preparation of palladium ultrafine particles The transition metal ultrafine particles used in the present invention were prepared in the same manner as described in Japanese Patent Application No. 2009-154932. Specifically, a rotator was placed in a three-necked flask, washed with DMF, DMF (15 mL) was added, and the three-necked flask was preheated at 140 ° C. for 6 minutes in an air atmosphere. Thereafter, 150 μL of 0.1 M palladium chloride aqueous solution was added, and the mixture was heated to reflux at 140 ° C. for 6 hours for synthesis. The palladium ultrafine particle solution is obtained as a 1 mM solution (1 mM Pd ultrafine particles (nanoparticles) (NCs) / DMF) and analyzed using an ultraviolet-visible absorption spectrum, fluorescence spectrum, and TEM. Was confirmed (FIG. 1A).
２．白金超微粒子の調製
上記パラジウム超微粒子と同様に、調製した。具体的には、三口フラスコに回転子を入れ、DMFで共洗いしたのちに、DMF (15 mL)を入れ、空気雰囲気下、140℃で6分間、三口フラスコを予備加熱した。その後、0.1 Mの塩化白金酸水溶液を75 μL加え、140℃、6時間加熱環流し合成を行った。白金超微粒子溶液は、1 mMの溶液 (1 mM Pt NCs／DMF)として得られ、紫外可視吸収スペクトル、蛍光スペクトル、TEMを用いて分析し、約1.5 nmの粒子の生成を確認した（図１（Ｂ））。
2. Preparation of platinum ultrafine particles Prepared in the same manner as the above-mentioned palladium ultrafine particles. Specifically, a rotator was placed in a three-necked flask, washed with DMF, DMF (15 mL) was added, and the three-necked flask was preheated at 140 ° C. for 6 minutes in an air atmosphere. Thereafter, 75 μL of 0.1 M chloroplatinic acid aqueous solution was added, and synthesis was carried out by refluxing at 140 ° C. for 6 hours. The platinum ultrafine particle solution was obtained as a 1 mM solution (1 mM Pt NCs / DMF) and analyzed using an ultraviolet-visible absorption spectrum, a fluorescence spectrum, and TEM to confirm the generation of particles of about 1.5 nm (FIG. 1). (B)).
［実施例］
［触媒の調製］
生成したパラジウム超微粒子溶液(Pd NCs／DMF)の1 mM溶液をDMFで100倍に希釈し、10 μM Pd NCs／DMFの溶液を調製した。さらに、10 μMのPd NCs／DMFの溶液をDMFで100倍に希釈し、100 nMの溶液を調製した。同様な操作で、10 nM、1 nMのPd NCs／DMF溶液を調製し、反応に用いた。
[Example]
[Preparation of catalyst]
A 1 mM solution of the produced palladium ultrafine particle solution (Pd NCs / DMF) was diluted 100 times with DMF to prepare a 10 μM Pd NCs / DMF solution. Further, a 10 μM Pd NCs / DMF solution was diluted 100 times with DMF to prepare a 100 nM solution. In the same manner, 10 nM and 1 nM Pd NCs / DMF solutions were prepared and used for the reaction.
同様に、1 mMのPd NCs／DMF溶液のDMF (15 mL)をエバポレーターにより留去したのち、NMP (15 mL)を加え、再分散させた。得られた1 mM Pd NCs／NMP溶液をNMPで100倍に希釈し、10 μMのPd NCs／NMP溶液を調製した。同様の操作で、1 μM、100 nM、10 nM、1 nMのPd NCs／NMP溶液を調製した。 Similarly, DMF (15 mL) of a 1 mM Pd NCs / DMF solution was distilled off using an evaporator, and then NMP (15 mL) was added and redispersed. The obtained 1 mM Pd NCs / NMP solution was diluted 100 times with NMP to prepare a 10 μM Pd NCs / NMP solution. In the same manner, 1 μM, 100 nM, 10 nM, and 1 nM Pd NCs / NMP solutions were prepared.
更に、1 mMのPd NCs／DMF溶液のDMF (15 mL)をエバポレーターにより留去したのち、THF(15 mL)を加え、再分散させた。得られた1 mM Pd NCs／THF溶液をTHFで100倍に希釈し、10 μMのPd NCs／THF溶液を調製した。同様の操作で、1 μM、100 nM、10 nM、1 nMのPd NCs／THF溶液を調製した。 Further, DMF (15 mL) of 1 mM Pd NCs / DMF solution was distilled off with an evaporator, and then THF (15 mL) was added to redisperse. The obtained 1 mM Pd NCs / THF solution was diluted 100 times with THF to prepare a 10 μM Pd NCs / THF solution. In the same manner, 1 μM, 100 nM, 10 nM, and 1 nM Pd NCs / THF solutions were prepared.
［クロスカップリング反応］
（溝呂木・ヘック反応）
[Cross coupling reaction]
(Mizorogi / Heck reaction)
プレッシャーチューブに回転子を入れ、アルゴン雰囲気のもと、上記［触媒の調製］で合成した1 mMのPd NCs／DMF (1 mL)を加えた。その後、ヨードベンゼン (1 mmol, 204 mg)、アクリル酸エチル (1.2 mmol, 120 mg)、トリエチルアミン (1 mmol, 101 mg)、溶媒としてDMF (1 mL)を加え、140℃、15時間反応を行った。定量は、GCを用い、内部基準法（基準物質はトリデカンである）で行った。ヘック型生成物の収率；定量的、触媒回転数；>1,000回。
A rotor was placed in the pressure tube, and 1 mM Pd NCs / DMF (1 mL) synthesized in the above [Preparation of catalyst] was added under an argon atmosphere. Then, iodobenzene (1 mmol, 204 mg), ethyl acrylate (1.2 mmol, 120 mg), triethylamine (1 mmol, 101 mg) and DMF (1 mL) as a solvent were added and reacted at 140 ° C for 15 hours. It was. Quantification was performed by GC using an internal standard method (the standard substance is tridecane). Heck product yield; quantitative, catalyst rotation;> 1,000 times.
（鈴木-宮浦クロスカップリング反応） (Suzuki-Miyaura cross-coupling reaction)
本発明の遷移金属超微粒子は触媒的クロスカップリング反応において極めて高い触媒活性を有することにより、希少金属資源の非常に効率的な利用が実現することができ、またクロスカップリング反応の生成物は、医薬品の合成中間体等としても有用であり、工業的に利用価値が高い。 The ultrafine transition metal particles of the present invention have a very high catalytic activity in the catalytic cross-coupling reaction, so that a very efficient utilization of rare metal resources can be realized, and the product of the cross-coupling reaction is It is also useful as a synthetic intermediate for pharmaceuticals and has high industrial utility value.
Claims (10)
（式中、
Ａは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、または無置換もしくは置換のアルケニル基であり；そして、
Ｘは、ハロゲン、メシレート基、トシレート基、トリフラート基、またはカルボン酸ハロゲン化物基である）
で示される化合物と、
式：Ｂ−Ｙ
（式中、
Ｂは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、無置換もしくは置換のアルケニル基、または無置換もしくは置換のアルキニル基であり；
Ｙは、水素、アリール基、アルコキシカルボニル基、ニトロ基、ホルミル基、オキソ基、シアノ基、アミノ基、Ｂ(ＯＲ１)２、ＺｎＸ１、ＡｌＲ２ ２、ＳｎＲ３ ３、ＭｇＸ２、またはＳｉＲ４ ３であり、ここで、Ｘ１およびＸ２はハロゲンであり、そしてＲ１、Ｒ２、Ｒ３およびＲ４は各々独立して水素またはアルキルである）
で示される化合物とを反応させることにより、
式：Ａ−Ｂ
（式中、ＡおよびＢは前掲する通りである）
で示される生成物を得るクロスカップリング反応用である、請求項１記載のクロスカップリング反応用触媒。 Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR 1 ) 2 , ZnX 1 , AlR 2 2 , SnR 3 3 , MgX 2 , or SiR 4 3, wherein, X 1 and X 2 is halogen and R 1, R 2, R 3 and R 4 are each independently hydrogen or alkyl)
By reacting with a compound represented by
Formula: AB
(In the formula, A and B are as described above.)
The catalyst for cross coupling reaction of Claim 1 which is an object for cross coupling reactions which obtains the product shown by these.
（式中、
Ａは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、無置換もしくは置換のアルケニル基、または無置換もしくは置換のアルキニル基であり；そして、
Ｘは、ハロゲン、メシレート基、トシレート基、トリフラート基、またはカルボン酸ハロゲン化物基である）
で示される化合物と、
式：Ｂ−Ｙ
（式中、
Ｂは、無置換もしくは置換のアリール基、無置換もしくは置換のヘテロアリール基、または無置換もしくは置換のアルケニル基であり；
Ｙは、水素、アリール基、アルコキシカルボニル基、ニトロ基、ホルミル基、オキソ基、シアノ基、アミノ基、Ｂ(ＯＲ１)２、ＺｎＸ１、ＡｌＲ２ ２、ＳｎＲ３ ３、ＭｇＸ２、またはＳｉＲ４ ３であり、ここで、Ｘ１およびＸ２はハロゲンであり、そしてＲ１、Ｒ２、Ｒ３およびＲ４は各々独立して水素またはアルキルである）
で示される化合物とを、請求項１記載のクロスカップリング反応用触媒の存在下で反応させることにより、式：Ａ−Ｂ
（式中、ＡおよびＢは前掲する通りである）
で示される生成物を得ることを含む、クロスカップリング反応。 Formula: AX
(Where
A is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, an unsubstituted or substituted alkenyl group, or an unsubstituted or substituted alkynyl group; and
X is a halogen, a mesylate group, a tosylate group, a triflate group, or a carboxylic acid halide group)
A compound represented by
Formula: BY
(Where
B is an unsubstituted or substituted aryl group, an unsubstituted or substituted heteroaryl group, or an unsubstituted or substituted alkenyl group;
Y is hydrogen, aryl group, alkoxycarbonyl group, nitro group, formyl group, oxo group, cyano group, amino group, B (OR 1 ) 2 , ZnX 1 , AlR 2 2 , SnR 3 3 , MgX 2 , or SiR 4 3, wherein, X 1 and X 2 is halogen and R 1, R 2, R 3 and R 4 are each independently hydrogen or alkyl)
Is reacted with the compound represented by formula (A-B) in the presence of the catalyst for cross-coupling reaction according to claim 1.
(In the formula, A and B are as described above.)
A cross-coupling reaction comprising obtaining a product represented by
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