Organic Chemistry Portal
Reactions >> Special Topics

Microwave Synthesis

It has long been known that molecules undergo excitation with electromagnetic radiation. This effect is utilized in household microwave ovens to heat up food. However, chemists have only been using microwaves as a reaction methodology for a few years. Some of the first examples gave amazing results, which led to a flood of interest in microwave-accelerated synthesis.

The water molecule is the target for microwave ovens in the home; like any other molecule with a dipole, it absorbs microwave radiation. Microwave radiation is converted into heat with high efficiency, so that "superheating" (external link) becomes possible at ambient pressure. Enormous accelerations in reaction time can be achieved, if superheating is performed in closed vessels under high pressure; a reaction that takes several hours under conventional conditions can be completed over the course of minutes.

Thermal vs. Nonthermal Effects

Excitation with microwave radiation results in the molecules aligning their dipoles within the external field. Strong agitation, provided by the reorientation of molecules, in phase with the electrical field excitation, causes an intense internal heating. The question of whether a nonthermal process is operating can be answered simply by comparing the reaction rates between the cases where the reaction is carried out under irradiation versus under conventional heating. In fact, no nonthermal effect has been found in the majority of reactions, and the acceleration is attributed to superheating alone. It is clear, though, that nonthermal effects do play a role in some reactions.

Is a Home Microwave Suitable for Organic Synthesis?

The discussion on the use of microwave units specially designed for synthesis use, which are often quite expensive, becomes rather heated at times. Unmodified home microwave units are suitable in some cases. However, simple modifications (for example, a reflux condenser) can heighten the safety factor. High-pressure chemistry should only be carried out in special reactors with a microwave oven specifically designed for this purpose. A further point in favor of using the more expensive apparatus is the question of reproducibility, since only these specialized machines can achieve good field homogeneity, and in some cases can even be directed on the reaction vessel.

Links of Interest

Microwave Chemistry Highlights
Laboratory Microwave Apparatus Manufacturers

Reviews on Microwave Synthesis

C. O. Kappe, "Controlled Microwave Heating in Modern Organic Synthesis", Angew. Chem. Int. Ed. 2004, 43, 6250. DOI

Books on Microwave Synthesis

Microwaves in Organic and Medicinal Chemistry

C. Oliver Kappe, Alexander Stadler
Hardcover, 410 Pages
First Edition, 2005
ISBN: 3-527-31210-2 - Wiley-VCH

Microwaves in Organic Synthesis

André Loupy
Hardcover, 499 Pages
First Edition, November 2002
ISBN: 3-527-30514-9 - Wiley-VCH

Recent Literature

Display all abstracts

A mild, green, and convenient one-pot carbon-chain extension of carboxylic acids with the assistance of microwaves and lithium chloride avoids the use of corrosive reagents, is tremendously faster than previously methods, and was free of configurational isomerization. Notably, LiCl played a dual role in the Krapcho decarboxylation and subsequent ester hydrolysis under neutral conditions.
C. Wang, J. Su, Y. Li, S. Gao, X. Huo, B. Yi, G. Zhao, Synlett, 2023, 34, 1033-1036.

A series of 1-alkoxy-3-methyl- and 3,4-dimethyl-3-phospholene 1-oxides, as well as 1-alkoxy-3-methylphospholane 1-oxides were prepared in good yields by a microwave-assisted and [bmim][PF6]-catalyzed transesterification of the corresponding methyl or ethyl esters.
N. Harsági, N. Z. Kiss, L. Drahos, G. Keglevich, Synthesis, 2022, 54, 3899-3905.

Synthesis of 2-Alkoxy-Substituted Thiophenes, 1,3-Thiazoles, and Related S-Heterocycles via Lawesson's Reagent-Mediated Cyclization under Microwave Irradiation:  Applications for Liquid Crystal Synthesis
A. A. Kiryanov, P. Sampson, A. J. Seed, J. Org. Chem., 2001, 66, 7925-7929.

[IPrH][F(HF)2] is a highly selective and soluble reagent for a microwave-assisted fluorination of various organic substrates. The scope of substrates includes benzyl bromides, iodides, chlorides, aliphatic halides, tosylates, mesylates, α-haloketones, a silyl chloride, acyl and sulfuryl chlorides, and a nitroarene. The reagent can be regenerated using hydrofluoric acid without organic solvents.
B. Alič, J. Petrovčič, J. Jelen, G. Tavčar, J. Iskra, J. Org. Chem., 2022, 87, 5987-5993.

A silicon nanoarray palladium catalyst mediates a hydrogenolysis of iodoarenes under microwave irradiation in the presence of triethanolamine as the sacrificial reductant. The reductive deiodination proceeded under an aerobic atmosphere affording the corresponding hydrogen-substituted arenes in high yields. No reaction occurred in the absence of microwaves.
Y. Matsukawa, Y. M. A. Yamada, Synlett, 2022, 33, 777-780.

Rapid Homogeneous-Phase Sonogashira Coupling Reactions Using Controlled Microwave Heating
M. Erdélyi, A. Gogoll, J. Org. Chem., 2001, 66, 4165-4169.

FeCl3 catalyzes a solvent-free sulfonylation of arenes under microwave irradiation. With more reactive and/or nonvolatile substrates (anisole, xylenes, mesitylene) a short reaction time at constant MW power without control of the temperature was used. With less reactive and/or low-boiling reagents (benzene, toluene, halobenzenes), the MW power was controlled. A nonthermal effect was not observed.
J. Marquié, A. Laporterie, J. Dubac, N. Roques, J.-R. Desmurs, J. Org. Chem., 2001, 66, 421-425.

The use of a magnetically recoverable palladium nanocatalyst supported on a green biochar enables an efficient palladium-catalyzed tandem reaction for the one-pot synthesis of 9H-carbazoles from inexpensive anilines and 1,2-dihaloarenes under microwave irradiation. The method shows a drastic reduction in reaction times and excellent compatibility with different functional groups.
H. S. Steingruber, P. Mendioroz, M. A. Volpe, D. C. Gerbino, Synthesis, 2021, 53, 2212-2218.

A highly efficient microwave-assisted Cu(I)-catalyzed cross-A3-coupling/decarboxylative coupling of two different amines, formaldehyde, and propiolic acid provides unsymmetric 1,4-diamino-2-butynes through a domino process in good yields with high chemoselectivity.
X. Xu, H. Feng, E. V. Van der Eycken, J. Org. Chem., 2021, 86, 14036-14043.

An efficient palladium-catalyzed reaction of N-propargyl oxazolidines provides 4-substituted isoquinolines under microwave irradiation through a sequential palladium-catalyzed reductive cyclization/ring-opening/aromatization cascade via C-O and C-N bond cleavages of the oxazolidine ring.
X. Xu, H. Feng, E. V. Van der Eycken, Org. Lett., 2021, 23, 6578-6582.

Aryl and vinyl nitriles have been prepared in very high yields from the corresponding bromides using palladium-catalyzed reactions under microwave irradiation. Furthermore, flash heating was used successfully for the conversion of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions. One-pot transformation of aryl halides directly to the aryl tetrazoles could also be accomplished.
M. Alterman, A. Hallberg, J. Org. Chem., 2000, 65, 7984-7989.

5-hydroxymethyl furfural is a biomass-derived commodity chemical that is ideal to prepare next-generation value-added products. Decarboxylative cross-couplings enable an efficient access to 2,5-diaryl furans. A key finding was that the presence of the hydroxymethyl handle enhances the yields of the first palladium-catalyzed decarboxylative cross-coupling reaction.
F. Chacón-Huete, J. D. Lasso, P. Szavay, J. Covone, P. Forgione, J. Org. Chem., 2021, 86, 515-524.

Environmentally Friendly Nafion-Mediated Friedländer Quinoline Synthesis under Microwave Irradiation: Application to One-Pot Synthesis of Substituted Quinolinyl Chalcones
C.-K. Chan, C.-Y. Lai, C.-C. Wang, Synthesis, 2020, 52, 1779-1794.

A copper-catalyzed imidoylative cross-coupling/cyclocondensation reaction between 2-isocyanobenzoates and amines efficiently provides quinazolin-4-ones. The reaction utilizes Cu(II) acetate as an environmentally benign catalyst in combination with a mild base and proceeds well in anisole, a sustainable solvent. The use of aromatic amines as nucleophiles requires microwave heating.
J. W. Collet, E. A. van der Nol, T. R. Roose, B. U. W. Maes, El Ruijter, R. V. A. Orru, J. Org. Chem., 2020, 85, 7378-7385.

An efficient catalyst-free radical cross-coupling reaction between aromatic aldehydes and sulfoximines took place in the presence of N-bromosuccinimide as the radical initiator under microwave irradiation to afford the corresponding acylated sulfoximines in good yields.
K. K. Rajbongshi, S. Ambala, T. Govender, H. G. Kruger, P. I. Arvidsson, T. Naicker, Synthesis, 2020, 52, 1279-1286.

Primary amines can be transformed into their corresponding pyridinium salts in the presence of glutaconaldehyde in acidic medium, including those substrates that remain unreactive toward the typically used Zincke salt.
G. Asskar, M. Rivard, T. Martens, J. Org. Chem., 2020, 85, 1232-1239.

Please cite and link this page as follows:

Microwave Synthesis ( URL: )