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
Microwave-promoted condensation of carbonyl compounds with (R)-2-methylpropane-2-sulfinamide under solvent-free conditions in the presence of Ti(OEt)4 enables a simple, environmentally friendly synthesis of optically pure N-(tert-butylsulfinyl)imines. Sulfinyl aldimines can be prepared with excellent yields and purities in only 10 min, whereas the reaction time for the preparation of ketimines has been extended to 1 h.
J. F. Collados, E. Toledano, D. Guijarro, M. Yus, J. Org. Chem., 2012, 77, 5744-5750.
An efficient microwave-assisted metal-free amino benzannulation of aryl(4-aryl-1-(prop-2-ynyl)-1H-imidazol-2-yl)methanone with dialkylamines affords various 2,8-diaryl-6-aminoimidazo[1,2-a]pyridines in good yield.
M. Nagaraj, M. Boominathan, S. Muthusubramanian, N. Bhuvanesh, Synlett, 2012, 1353-1357.
Sequential coupling-imination-annulation reactions of ortho-bromoarylaldehydes and terminal alkynes with ammonium acetate in the presence of a palladium catalyst under microwave irradiation gives various substituted isoquinolines, furopyridines, and thienopyridines in good yields.
D. Yang, S. Burugupalli, D. Daniel, Y. Chen, J. Org. Chem., 2012, 77, 4466-4472.
N-Sulfonyl-1,2,3-triazoles react with water in the presence of a rhodium catalyst to produce α-amino ketones in high yield. This transformation formally achieves 1,2-aminohydroxylation of terminal alkynes in a regioselective fashion in combination with a copper(I)-catalyzed 1,3-dipolar cycloaddition with N-sulfonyl azides.
T. Miura, T. Biyajima, T. Fujii, M. Murakami, J. Am. Chem. Soc., 2012, 134, 194-196.
A versatile microwave-assisted procedure for the palladium-catalyzed direct arylation of heterocycles by aryl bromides and heteroaryl bromides features short coupling times (10–60 min) and low catalyst loadings and allows the successful arylation of previously unreactive heterocyclic substrates.
M. Baghbanzadeh, C.Pilger, C. O. Kappe, J. Org. Chem., 2011, 76, 8138-8142.
An easy three-step pathway enabled the synthesis of arylacetaldehydes from the corresponding carboxylic acids in very high yields. A subsequent microwave-assisted Gewald reaction gives 5-substituted-2-aminothiophenes in short time, with high yields and purities.
G. Revelant, S. Dunand, S. Hesse, G. Kirsch, Synthesis, 2011, 2935-2940.
A straightforward and efficient Yb(OTf)3 catalyzed three-component reaction of aldehydes, alkynes, and amines under microwave irradiation in an ionic liquid provides 2,4-disubstituted quinolines in excellent yield under mild reaction condition. The catalyst can be recycled up to four times.
A. Kumar, V. K. Rao, Synlett, 2011, 2157-2162.
3,3′-Br2-BINOL catalyze the enantioselective asymmetric propargylation of ketones using allenyldioxoborolane as nucleophile, in the absence of solvent, and under microwave irradiation to afford homopropargylic alcohols in good yields and high enantiomeric ratios. Diastereoselective propargylations using chiral racemic allenylboronates result in good diastereoselectivities.
D. S. Barnett, S. E. Schaus, Org. Lett., 2011, 13, 4020-4023.
A facile, efficient, and large-scale strategy for the synthesis of N-(1-Oxo-1H-inden-2-yl)benzamide derivatives via domino reaction between aryl aldehydes, hippuric acid, and acetic anhydride is catalyzed by HPW@nano-SiO2 under microwave irradiation. The reaction conditions are very simple and offer convenient isolation of the product. Moreover, the catalyst can be re-used up to five times after simple filtration.
M. Rostami, A. R. Khosropour, V. Mirkhani, I. Mohammadpoor-Baltork, M. Moghadam, S. Tangestaninejad, Synlett, 2011, 1677-1682.
ZrOCl2 • 8 H2O is a highly effective, water-tolerant, and reusable catalyst for the direct condensation of carboxylic acids and N,N′-dimethylurea under microwave irradiation to give the corresponding N-methylamides in moderate to excellent yields. ZrOCl2 • 8 H2O is a useful green catalyst due to its low toxicity, easy availability, low cost, ease of handling, easy recovery, good activity, and reusability.
D. Talukdar, L. Saikia, A. J. Thakur, Synlett, 2011, 1597-1601.
An efficient and simple protocol for phosphine-free Heck reactions in water in the presence of a Pd(L-proline)2 complex as the catalyst under controlled microwave irradiation conditions is versatile and provides excellent yields of products in short reaction times. The reaction system minimizes costs, operational hazards and environmental pollution.
B. K. Allam, K. N. Singh, Synthesis, 2011, 1125-1131.
Microwave heating enables a Borrowing Hydrogen strategy to form C-N bonds from alcohols and amines, removes the need for solvent and reduces the reaction times, while the results are comparable with those using thermal heating.
A. J. A. Watson, A. C. Maxwell, J. M. J. Williams, J. Org. Chem., 2011, 76, 2328-2331.
An organocatalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and trimethylsilyl chloride, enables the formation of tetrazoles by cycloaddition of sodium azide with organic nitriles under neutral conditions and microwave heating. The organocatalyst accelerates the azide-nitrile coupling by activating the nitrile substrate.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.
High-speed and scalable nickel-catalyzed cross-coupling of arylboronic acids with aryl carbamates and sulfamates is achieved by using sealed-vessel microwave processing.
M. Baghbanzadeh, C. Pilger, C. O. Kappe, J. Org. Chem., 2011, 76, 1507-1510.
An efficient and simple method enables the N-alkylation of aromatic cyclic imides using cesium carbonate as the base in anhydrous N,N-dimethylformamide at low temperatures (20-70˚C). The employment of microwave irradiation presents noteworthy advantages over conventional heating. The method is compatible with base labile functional groups.
M. I. Escudero, L. D. Kremenchuzky, I. A. Perillo, H. Cerecetto, M. M. Blanco, Synthesis, 2011, 571-576.
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