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
www.maos.net - MICROWAVE-ASSISTED ORGANIC SYNTHESIS (MAOS) WEBPAGES
www.cyf-kr.edu.pl/~pcbogdal/ - Darek Bogdal's Page with some literature citations
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
Hardcover, 499 Pages
First Edition, November 2002
ISBN: 3-527-30514-9 - Wiley-VCH
A microwave-assisted hydrophosphinylation of unactivated alkenes with phosphinic acid and its derivatives under metal- and initiator-free conditions is operationally simple and seems to proceed via a radical mechanism. Good isolated yields were obtained using a reasonable excess of the appropriate reagent.
P. Troupa, G. Katsiouleri, S. Vassiliou, Synlett, 2015, 26, 2714-2719.
A protocol with small amounts of palladium and ligand, without any additive solvent and under microwave heating enables cross-coupling reactions between 2-methyl-2-propen-1-ol and various boronic acids to yield aromatic 2-methylallyl derivatives.
C. Tabélé, C. Curti, N. Primas, Y. Kabri, V. Remusat, P. Vanelle, Synthesis, 2015, 47, 3339-3346.
A mild gold-catalyzed protodeboronation reaction can be carried out in green solvents without any acid or base additives. Therefore, the reaction is very functional-group-tolerant and enables the use of the boronic acid group as an effective traceless directing or blocking group.
G. Barker, S. Webster, D. G. Johnson, R. Curley, M. Andrews, P. C. Young, S. A. Macgregor, A.-L. Lee, J. Org. Chem., 2015, 80, 9807-9816.
Enyne cross metathesis of propargylamines with ethyl vinyl ether provides a series of substituted pyrroles, bearing alkyl, aryl, and heteroaryl substituents under microwave irradiation.
H. Chachignon, N. Scalacci, E. Petricci, D. Castagnolo J. Org. Chem., 2015, 80, 5287-5295.
A microwave-assisted method for the palladium-catalyzed direct arylation of quinazolin-4-one has been developed under copper-assistance. This method is applicable to a wide range of aryl iodides and substituted (2H)-quinazolin-4-ones. This protocol provides a simple and efficient way to synthesize biologically relevant 2-arylquinazolin-4-one backbones.
S. Laclef, M. Harari, J. Godeau, I. Schmitz-Afonso, L. Bischoff, C. Hoarau, V. Levacher, C. Fruit, T. Besson, Org. Lett., 2015, 17, 1700-1703.
A gold-catalyzed, microwave protocol activates alcohols through an intermolecular, SN1-type reaction to directly form unsymmetrical ethers and Cbz-protected amines in good yields. This reaction is highly reproducible and tolerates moisture.
A. R. S. Vinson, V. K. Davis, A. Arunasalam, K. A. Jesse, R. E. Hamilton, M. A. Shattuck, A. C. Hu, R. G. Iafe, A. G. Wenzel, Synlett, 2015, 26, 765-770.
Triflic anhydride activation followed by microwave-induced cyclodehydration enables a one-pot synthesis of 3,4,5-trisubstituted 1,2,4-triazoles from secondary amides and hydrazides. In addition, the 1,2,4-triazole moiety is shown to be a useful directing group for Ru-catalyzed C-H arylation. A Pd-catalyzed intramolecular C-H functionalization reaction allows access to 1,2,4-triazolophenanthridine.
W. S. Bechara, I. S. Khazhieva, E. Rodriguez, A. B. Charette, Org. Lett., 2015, 17, 1184-1187
A simple, efficient, and mild method for the synthesis of substituted 1,2,4-triazoles from hydrazines and formamide proceeds smoothly under microwave irradiation in the absence of a catalyst and shows excellent functional-group tolerance.
G. M. Shelke, V. K. Rao, M. Jha, T. S. Cameron, A. Kumar, Synlett, 2015, 26, 404-407.
Microwave-promoted iminyl radical cyclizations can be terminated by trapping with TEMPO, affording functionalized adducts without using toxic and hazardous reagents. The use of alkynes as radical acceptors delivers a range of 2-acylpyrroles in good yields.
Y. Cai, A. Jalan, A. R. Kubosumi, S. L. Castle, Org. Lett., 2015, 17, 488-491.
A combination of copper(II) oxide and 1,10-phenanthroline catalyzes a microwave-promoted C-S bond formation of thiols and aryl iodides. Various aryl iodides react smoothly with thiols to provide the corresponding aryl sulfides in very good yields in water with a short reaction time. Amino, chloro, bromo, acetyl, and nitro groups are tolerated.
Y.-A. Chen. S. S. Badsara, W.-T. Tsai, C.-F. Lee, Synthesis, 2015, 47, 181-186.
TiO2-supported nanosize gold particles catalyze the hydration of alkynes using morpholine as a basic cocatalyst. As the TiO2-Au/morpholine system is weakly basic, the reaction tolerates acid-sensitive functional groups (e.g., silyl ethers, ketals) and strongly coordinating group such as pyridine. In addition, the gold catalyst can be recycled by simple filtration and works well in flow reactors.
S. Liang, J. Jasinski, G. B. Hammond, B. Xu, Org. Lett., 2015, 17, 162-165.
Benzimidazoles and quinoxalin-2(1H)-ones were synthesized by treatment of 2-(N-Boc-amino)phenylisocyanide with carboxylic acids and glyoxylic acids, respectively via two-component coupling, deprotection, and intermolecular cyclization.
Z.-Z. Chen, Y. Tang, L. Zuo, D.-Y. Tang, J. Zhang, Z.-G. Xu, Synlett, 2014, 25, 2518-2520.
An efficient hydrosulfonylation of alkynes using sodium arene sulfinates is catalyzed by Cu(OTf)2 under microwave irradiation.Various vinyl sulfones were obtained in very good yields and with high regio- and stereoselectivity. Short reaction times, simple reaction conditions and low catalyst loading are the remarkable features of this protocol.
G. M. Shelke, V. K. Rao, K. Pericherla, A. Kumar, Synlett, 2014, 25, 2345-2349.
A MW-based protocol enables a rapid preparation of 1,1-difluorocyclopropanes, using fluorinated acetate salts. The new procedure is not only considerably faster than conventional methods, but it also employs easily removed, low boiling-point solvents and avoids the use of highly toxic or ozone-depleting substances.
D. M. Gill, N. McLay, M. J. Waring, C. T. Wilkinson, J. B. Sweeney, Synlett, 2014, 25, 1756-1758.
Microwave irradiation enables an expeditious one-pot, ligand-free, Pd(OAc)2-catalyzed, three-component reaction for the synthesis of 2,3-diarylimidazo[1,2-a]pyridines. This methodology offers high availability of commercial reagents and great efficiency in expanding molecule diversity.
Y. Wang, B. Frett, H.-y. Li, Org. Lett., 2014, 16, 3016-3019.
Please cite and link this page as follows:
Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )