マイクロ波合成

従来の合成法のボトルネックとなっていたのは、最適化のステップ、すなわち、目的の生成物を良好な収率と純度で得るために特定の反応の最適条件を見つけることでした。多くの合成反応は、長時間にわたって1つ以上の加熱ステップを必要とするため、こうした最適化はしばしば困難で時間のかかるものでした。条件を制御してマイクロ波で加熱する手法は、反応時間が劇的に短縮されることが多いため（一般的には数日または数時間から数分または数秒にまで短縮）、反応混合物の加熱を必要とするあらゆる用途において価値ある手法であることが示されています。この手法を使えば、並行して、あるいは（自動的に）連続して、化合物を迅速に合成することができます。

複数のバリエーションの反応条件を迅速に実行できるため、朝の「何を試すべきか」という議論が、昼食後には「結果はどうだったか」という議論になります。当然のことながら、ほとんどの製薬会社、農薬会社、バイオテクノロジー会社、マテリアルサイエンス会社は、化学研究室の主要な手法として、すでにマイクロ波合成を多用しています。こうした企業は、マイクロ波技術には化学反応を加速させ、そして生産プロセス全体を加速させる能力があることを理解しています。^[7]

以下では、マイクロ波が有効であることが証明されている合成アプリケーションを紹介します。

• 金属触媒による結合形成反応 
• Nヘテロ環の合成 
• OおよびSヘテロ環の合成 
• 炭素環と転位
• スカフォールド デコレーション
• 触媒、配位子、錯体の合成 
• 酸化 
• ナノマテリアル
  • グラフェンとカーボンナノ粒子 
  • 電池研究用ナノマテリアル 
  • チタニア、亜鉛、鉄、各種金属酸化物 
  • カルコゲード 
  • 金属、ナノ合金 
  • ゼオライト、モレキュラーシーブ 
  • 量子ドット 
  • 金属有機構造体 
• 高分子化学 
• イオン液体の合成とイオン液体を用いた合成 
• 水、亜臨界水、超臨界流体での反応 
• バイオディーゼル/バイオマス関連のアプリケーション 
• 脱乳化と原油関連反応 
• マイクロ波とフローケミストリーの比較 
• マイクロ波効果の研究 

1. Leadbeater, N. (2004). Chemistry World, 1, 38 

2. Adam, D. (2003). Nature, 421, 571

3. Marx, V. (2004). Chem. & Eng. News, 82, 14; 

4. Yarnell, A. (2007). Chem. & Eng. News, 85, 32.

5. Gedye R. et al. (1986). Tetrahedron Lett., 27, 279; 

6. Giguere, R. J. et al. (1986). Tetrahedron Lett., 27, 4945.

7. Kappe, C. O., Stadler, A., Dallinger, D. (2012). Microwaves in Organic and Medicinal Chemistry, 2nd Edition. Wiley-VCH, Weinheim.

8. SciFinder scholar search (keyword search: “microwave”) for seven selected synthetic organic chemistry journals: J. Org. Chem., Org. Lett., Tetrahedron, Tetrahedron Lett., Synth. Commun., Synthesis, Synlett.

9. SciFinder scholar search (full text search: “microwave”) for approx. 50 journals. Data for recent years are not available but are estimated to be far higher than for 2008 (in the range of approx. 1000 to 1200 publications per year).

10. J. Org. Chem. 2015, Author Guidelines.

11. Neas, E., Collins, M. (1988). Introduction to Microwave Sample Preparation: Theory and Practice (Eds.: Kingston, H. M., Jassie, L. B.), American Chemical Society, Washington, DC.

12. Herrero, M. A., Kremsner, J. M., Kappe, C. O. (2008). J. Org. Chem., 73, 36.

以下は過去10年間のマイクロ波合成に関する科学論文の一覧です。

Microwave-assisted metal-catalyzed reactions

• P. K. Singh et al. 2018. “Aminopyrimidine class aggregation inhibitor effectively blocks Aβ-fibrinogen interaction and Aβ-induced contact system activation,” Biochemistry, 57: 1399.
• Metallosurfactant based Pd-Ni Alloy Nanoparticles as proficient catalyst in Mizoroki Heck Coupling Reaction, N. Kaur et al., Green Chem. 2018, 20, 1506.
• Complex Polycycles from Simple Propargyl Alcohols through Ruthenium-Catalyzed Cascade Reactions and One-Pot Procedures, E. Jäckel et al., Synthesis 2018, 50, 742.
• Divergent synthesis of 1,2-benzo[e]thiazine and benzo[d]thiazole analogs containing a S-trifluoromethyl sulfoximine group. Preparation and new properties of the Adachi reagent, A.-L. Barthelemy et al., J. Org. Chem. 2019, 84, 4086.

Microwave-assisted synthesis of N-heterocycles

• Microwave-assisted one-pot synthesis of new phenanthrene fused-tetrahydrodibenzo-acridinones as potential cytotoxic and apoptosis inducing agents, N. P. Kumar et al., Eur. J. Med. Chem. 2018, 151, 173.
• Copper complexes bearing C-scorpionate ligands: Synthesis, characterization and catalytic activity for azide-alkyne cycloaddition in aqueous medium, A. G. Mahmoud et al., Inorg. Chim. Acta 2018, 483, 371.
• Organocatalytic aza-Michael Reaction to 3-Vinyl-1,2,4-Triazines as a Valuable Bifunctional Platform,
• F. Buttard et al., J. Org. Chem. 2019, 84, 3702.
• Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi–Mumm and regiospecific quinazolinone rearrangements, V. A. Jaffett et al., Org. Biomol. Chem. 2019, 17, 3118.
• Aziridination and aza-Wharton Reactions of Levoglucosenone, E. T. Ledingham et al., Aust. J. Chem. 2019, 72, 362.

Microwave-assisted synthesis of O- and S-heterocycles

• Microwave-assisted synthesis of novel benzodifuran-based bis(N-(het)arylthiazol-2-amine) derivatives and their antibacterial and antimycobacterial activities, N. H. K. Baba et al., Chem. Heterocycl. Comp. 2018, 54, 658.
• Structure-activity relationship of anticancer potential of 4-hydroxycoumarin and its derivatives:
  A comparative study, S. M. Banday et al., Asian J. Pharm. Pharmacol. 2019, 5, 470.

Microwave-assisted rearrangements

• Synthetic and Mechanistic Study on the Microwave Assisted Fries Rearrangement of 1-Methylidene-3,4-dihydroisoquinoline-2(1H)-yl-methanones, F. Haraszti et al., Curr. Org. Chem. 2018, 22, 912.
• Montmorillonite K10-Catalyzed Solvent-Free Conversion of Furfural into Cyclopentenones, S. Bonacci et al., Catalysts 2019, 9, 301.

Microwave-assisted scaffold decoration

• Base-controlled regioselective functionalization of chloro-substituted quinolines, V. E. Murie et al., J. Org. Chem. 2018, 83, 871.
• Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action, M. V. Raimondi et al., Bioorg. Med. Chem. 2019, 27, 721.
• On the synthesis, optical and computational studies of novel BODIPY-based phosphoramidate fluorescent dyes, L. A. Machado et al., J. Fluorine Chem. 2019, 220, 9.

Microwave-assisted catalysts, ligands & complexes

• Multifunctional Cyclopentadiene as a Scaffold for Combinatorial Bioorganometallics in
  [(η5‐C5H2R1R2R3)M(CO)3] (M = Re, 99mTc) Piano‐stool Type Complexes, A. Frei et al., Chem. Eur. J. 2018, 24, 10153.
• Whole Microwave Syntheses of Pyridylpyrazole and of Re and Ru Luminescent Pyridylpyrazole Complexes, B. Merillas et al., Inorg. Chim. Acta 2019, 484, 1.
• Tuning the Luminescent Properties of Ruthenium(II) Amino‐1,10‐Phenanthroline Complexes by Varying the Position of the Amino Group on the Heterocycle, A. S. Abel et al., ChemPlusChem 2019, 84, 498.

Microwave-assisted oxidations

• Copper(II) complexes with an arylhydrazone of methyl 2-cyanoacetate as effective catalysts in the microwave-assisted oxidation of cyclohexane, R. Jlassi et al., Inorg. Chim. Acta 2018, 471, 658.
• Synergistic catalytic action of vanadia–titania composites towards the microwave-assisted benzoin oxidation, F. Ferretti et al., Dalton Trans. 2019, 48, 3198.

Various microwave-assisted organic transformations

• Tropylium-promoted Carbonyl-Olefin Metathesis Reactions, U. P. N. Tran et al., Chem. Sci. 2018, 9, 5145.
• Hydrogen-Bonding-Assisted Ketimine Formation of Benzophenone Derivatives, M.-S. Seo et al., J. Org. Chem. 2018, 83, 14300.
• Efficient Semi-Synthesis of Natural δ-(R)-Tocotrienols from a Renewable Vegetal Source, A. Ville et al., J. Nat. Prod. 2019, 82, 51.
• A New Alternative Synthesis of Salicylaldazine via Microwave Irradiation Method, K. et al., J. Chem. 2019, 9546373.

Microwave-assisted synthesis of nanomaterials

• Simultaneous desulfuration and denitrogenation of model diesel fuel by FeMn microwave modified activated carbon: Iron crystalline habit influence on adsorption capacity, J. A. Arcibar-Orozco et al., J. Clean. Prod. 2019, 218, 69.
• Structural Impact of Zn-insertion into Monoclinic V2(PO4)3: Implications for Zn-ion Batteries, M. J. Park et al., J. Mater. Chem. A 2019, 7, 7159.
• Glyme-Based Electrolyte for Na/Bilayered V2O5 Batteries, X. Liu et al., ACS Appl. Energy Mater. 2019, 2, 2786.
• Self-assembly of hybrid nanorods for enhanced volumetric performance of nanoparticles in Li-ion batteries, M. H. Modarres et al., Nano Lett. 2019,19, 228.
• Nanostructuring of 1-butyl-4-methylpyridinium chloride in ionic liquid–iron oxide nanofluids, A. Joseph et al., J. Therm. Anal. Calorim. 2019, 135, 1373.
• Synthesis of iron oxide nanorods for enhanced magnetic hyperthermia, A. Nikitin et al.,
  J. Magn. Magn. Mater. 2019, 469, 443.
• Hydrothermal microwave synthesis of SnO microspheres with excellent photocatalytic activity, D. Han et al., Ceram. Int. 2019, 45, 4089.
• Effect of Deposition Time on the Optoelectronics Properties of PbS Thin Films Obtained by Microwave-Assisted Chemical Bath Deposition, E. Barrios-Salgado et al., Adv. Cond. Matter Phys. 2019, 5960587.
• In Situ Microwave‐Assisted Fabrication of Hierarchically Arranged Metal Sulfide Counter Electrodes
  to Boost Stability and Efficiency of Quantum Dot‐Sensitized Solar Cells, J.‐S. Tsai et al., Adv. Mater. Interf. 2019, 6, 1801745.
• Microwave assisted κ-carrageenan capped silver nanocomposites for eradication of bacterial biofilms,
  A. Goel et al., Carbohyd. Polym. 2019, 206, 854.
• Microwave-green synthesis of AlPO-n and SAPO-n (n= 5 and 18) nanosized crystals and their assembly in layers, E.-P.Ng et al., Micropor. Mesopor. Mater. 2019, 280, 256.
• XANES, EXAFS, EPR and First Principles Modeling on Electronic Structure and Ferromagnetism in Mn Doped SnO2 Quantum Dots, D. Manikandan et al., J. Phys. Chem. C 2019, 123, 3067.
• Synthesis and characterization of Polymer/Silica/QDs fluorescent nanocomposites with potential application as printing toner, M. Ruiz-Robles et al., Mater. Res. Express 2019, 6, 25314.
• Microwave-Assisted Hydrothermal Synthesis of Agglomerated Spherical Zirconium Phosphate for Removal of Cs+ and Sr2+ Ions from Aqueous System, A. Bashir et al., Applic. Ion Exchange Mater. Environ. 2019, 95.
• A co-operative endeavor by nitrifying bacteria Nitrosomonas and Zirconium based Metal Organic Framework to remove hexavalent chromium, T. Sathvika et al., Chem. Eng. J. 2019, 360, 879.

Microwave-assisted polymer chemistry

• Exfoliation, reduction, hybridization and polymerization mechanisms in one-step microwave-assist synthesis of nanocomposite nylon-6/graphene, P. González-Morones et al., Polymer 2018, 146, 73.
• Synthesis, characterization and chemical degradation of poly(ester-triazole)s derived from D-galactose, M. V. Rivas et al., RSC Adv. 2019, 9, 9860.
• Microwave-assisted esterification step of poly(ethylene terephthalate) (PET) synthesis through ethylene glycol and terephthalic acid, A. C. Espinosa-López et al., Polym. Bull. 2019, 76, 2931.

Microwave-assisted synthesis of and with ionic liquids

• Imidazolium based Ionic liquids as efficient reagents for lignin C-O bond cleavage, M. Thierry et al., ChemSusChem 2018, 11, 439.
• New poly(ionic liquid)s based on poly(azomethine-pyridinium) salts and its use as heterogeneous catalysts for CO2 conversion, E. M. Maya et al., Eur. Polym. J. 2019, 110, 107.

Microwave-assisted biodiesel- and biomass-related applications

• Conversion of sunflower stalk based cellulose to the valuable products using choline chloride based deep eutectic solvents, M. Sert et al., Renew. Energy 2018, 118, 993.
• A synergetic effect of ionic liquid and microwave irradiation on the acid-catalyzed direct conversion of cellulose into methyl glucopyranoside, M. Saito et al., Holzforschung 2018, 72, 1025.
• Microwave assisted biodiesel production using a novel Brønsted acid catalyst based on nanomagnetic biocomposite, S. Chellappan et al., Fuel 2019, 246, 268.

マイクロ波を用いたマイクロ波効果の研究

• Specific microwave effect on Sn- and Ti-MFI zeolite synthesis, Z. Sun et al., RSC Adv. 2017, 7, 35252.
• Microwave effects in the dilute acid hydrolysis of cellulose to 5-hydroxymethylfurfural, N. Sweygers, 
  et al., Nat. Sci. Rep. 2018, 8, 7719.
• Synthesis of Highly Uniform Nickel Multipods with Tunable Aspect Ratio by Microwave Power Control, 
  P. N. Vakil et al., ACS Nano 2018, 12, 6784.

• Advances in Microwave Chemistry, B. K. Banik, D. Bandyopadhyay (Eds.), 2018, CRC Press, Taylor & Francis Group, Boca Raton
• A Chemist’s Guide to Microwave Synthesis, Volume 3, J. M. Kremsner, A. Stadler, 2018, Anton Paar Publishing, Austria
• Solid-Phase Organic Syntheses, Volume 3: Microwave-Assisted Solid-Phase Organic Synthesis, P. J. H. Scott (Ed.), 2017, Wiley-VCH, Weinheim
• Advances in Microwave Chemistry, B. K. Banik, D. Bandyopadhyay (Eds.), 2018, CRC Press, Taylor & Francis Group, Boca Raton
• Solid-Phase Organic Syntheses, Volume 3: Microwave-Assisted Solid-Phase Organic Synthesis, P. J. H. Scott (Ed.), 2017, Wiley-VCH, Weinheim
• Microwave-assisted Polymer Chemistry, R. Hoogenboom, U. S. Schubert, F. Wiesbrock (Eds.), 2016, Springer, Berlin
• Milestones in Microwave Chemistry, G. Keglevich (Ed.), 2016, Springer, Berlin
• Microwaves in Catalysis: Methodology and Applications, S. Horikoshi, N. Serpone, 2015, Wiley-VCH, Weinheim
• Microwave-assisted Polymerization, A. Mishra, T. Vats, J. H. Clark, 2015, Royal Society of Chemistry, London
• Microwave-Assisted Synthesis of Heterocycles, E. van der Eycken, C. O. Kappe, 2014, Springer, Berlin
• Microwave-Assisted Organic Synthesis: A Green Chemistry Approach, S. C. Ameta, P. B. Punjabi, R. Ameta, C. Ameta (Eds.), 2014, Apple Academic Press, Waretown
• Microwaves in Drug Discovery and Development: Recent Advances, J. Spencer, M. C. Bagley (Eds.), 2014, Future Science Group, London
• Microwaves in Nanoparticle Synthesis: Fundamentals and Applications, S. Horikoshi, N. Serpone, 2013, Wiley-VCH, Weinheim
• Microwaves in Organic and Medicinal Chemistry, C. O. Kappe, D. Dallinger, A. Stadler, 2nd edition, 2012, Wiley-VCH, Weinheim
• Microwaves in Organic Synthesis, A. De La Hoz, A. Loupy (Eds.), 3rd edition, 2012, Wiley-VCH, Weinheim
• Microwave-assisted Cycloaddition Reactions, D. Margetic, 2011, Nova Science Publishers, Hauppauge
• Aqueous Microwave-assisted Chemistry, V. Polshettiwar, R. S. Varma (Eds.), 2010, RSC Publishing, Cambridge
• Practical Microwave Synthesis for Organic Chemists, C. O. Kappe, D. Dallinger, S. S. Murphree, 2009, Wiley-VCH, Weinheim
• Microwave-assisted Proteomics, J. R. Lill, 2009, RSC Publishing, Cambridge
• Microwave-assisted Synthesis of Heterocycles, E. van der Eycken, C. O. Kappe (Eds.), 2006, Springer, Berlin
• Microwave methods in Organic Synthesis, M. Larhed, K. Olofsson (Eds.), 2006, Springer, Berlin
• Microwave-assisted Organic Synthesis: 100 reaction procedures, D. Bogdal, 2005, Elsevier, Amsterdam
• Microwave-assisted Organic Synthesis, J. P. Tierney, P. Lidström (Eds.), 2005, Blackwell, Oxford