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

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.

A simple microwave-accelerated condensation of 2-aminothiophenol and aromatic aldehyde in an inexpensive ionic liquid, 1-pentyl-3-methylimidazolium bromide ([pmIm]Br) provides 2-arylbenzothiazoles under solvent and catalyst-free condition. The ionic liquid can be recycled for subsequent reactions.
B. C. Ranu, R. Jana, S. S. Dey, Chem. Lett., 2004, 286-287.

A monobenzylation of aromatic amines with benzylic alcohols in good yields proceeds under MW conditions in the presence of SmI2 as a catalyst with the generation of water as the sole byproduct. This reaction offers a broad substrate scope and good functional-group tolerance.
J. Gour, S. Gatadi, S. Malasala, M. V. Yaddanpudi, S. Nanduri, J. Org. Chem., 2019, 84, 7488-7494.

An efficient and convenient Ni-catalyzed C-N bond formation enables the synthesis of various benzimidazoles in excellent yields from various 2-haloanilines, aldehydes, and ammonia as nitrogen source.
F. Ke, P. Zhang, Y. Xu, X. Lin, J. Lin, C. Lin, J. Xu, Synlett, 2018, 29, 2722-2726.

A catalyst-free amination of 2-mercaptobenzoxazoles on water under microwave irradiation provides 2-aminobenzoxazoles in good yields via direct amination. Key benefits of this process include an on-water reaction, short reaction time, being scalable and catalyst-free, and use of 2-mercaptobenzoxazoles as an inexpensive starting material.
T. Tankam, J. Srisa, M. Sukwattanasinitt, S. Wacharasindhu, J. Org. Chem., 2018, 83, 11936-11943.

An AgOTf-catalyzed reaction of β-(2-Aminophenyl)-α,β-ynones provides 3-unsubstituted 2-acylindoles in good yields under microwave heating. The use of Cu(OTf)2 as a catalyst resulted in a similar reaction outcome, albeit with a lower efficiency.
N. D. Rode, I. Abdalghani, A. Arcadi, M. Aschi, M. Chiarini, F. Marinelli, J. Org. Chem., 2018, 83, 6354-6362.

Formation of enamino ketones from 1-(2-hydroxyphenyl)ethanone derivatives under microwave heating followed by cyclization using T3P® provides 4H-chromene-4-ones in short reaction times and high purity.
C. Balakrishna, V. Kandula, R. Gudipati, S. Yennam, P. U. Devi, M. Behera, Synlett, 2018, 29, 1087-1091.

A practical and general microwave-mediated Biginelli cyclocondensation of guanidine with aldehydes and β-dicarbonyl compounds provides functionalized 2-amino-3,4-dihydropyrimidines in good yields, with short reaction times and a simple workup. The scope is considerably wider than that of similar reactions carried out under conventional heating.
F. Felluga, F. Benedetti, F. Berti, S. Drioli, G. Regini, Synlett, 2018, 29, 986-992.

DABCO promotes an efficient, solvent-free, and eco-friendly domino reaction of various β,γ-unsaturated α-ketocarbonyls with 5/6-membered cyclic sulfamidate imines in neat conditions under MW irradiation to provide densely functionalized picolinates in short reaction times.
S. Biswas, D. Majee, S. Guin, S. Samanta, J. Org. Chem., 2017, 82, 10928-10938.

A transition-metal-free synthesis of a series of primary arylamines from potassium aryltrifluoroborates and phenylboronic acids uses hydroxylamine-O-sulfonic acid as a mild, inexpensive source of nitrogen in cooperation with aqueous sodium hydroxide in acetonitrile. Both a sonication and a microwave-assisted method were developed.
D. Kuik, J. A. McCubbin, G. K. Tranmer, Synthesis, 2017, 49, 2555-2561.

Please cite and link this page as follows:

Microwave Synthesis ( URL: )