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
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.
Use of the heterogeneous catalyst amberlist-15 A enables an efficient synthesis of N-(tert-butylsulfinyl)imines under microwave irradiation. Amberlist-15 is convenient to handle, inexpensive, safe to use and quickly separable from the reaction mixture. This method offers a number of advantages including operational simplicity, high yield of products, and broad substrate scope.
C. Sanaboina, S. Jana, L. Eppakayala, Synlett, 2014, 25, 1006-1008.
Microwave-assisted conditions enabled a simple, rapid, one-pot synthesis of arylaminomethyl acetylenes in very good yields using arylboronic acids, aqueous ammonia, propargyl halides, copper(I) oxide and water as the solvent within ten minutes.
Y. Jiang, S. Huang, Synlett, 2014, 25, 407-410.
Solvent-free, base-free microwave-mediated (Cp*IrCl2)2-catalyzed conditions for the N-alkylation of amides with a series of primary and secondary alcohols produce high yields of N-alkyl arylamides and N-alkyl alkylamides.
T. D. Apsunde, M. L. Trudell, Synthesis, 2014, 46, 230-234.
The addition of Grignard reagents or organolithium reagents to the SO2-surrogate DABSO generates a diverse set of metal sulfinates, which can be trapped in situ with a wide range of C-electrophiles, including alkyl, allyl, and benzyl halides, epoxides, and (hetero)aryliodoniums to give sulfone products.
A. S. Deeming, C. J. Russell, A. J. Henessy, M. C. Willis, Org. Lett., 2014, 16, 150-153.
A deep eutectic mixture of choline chloride and urea (1:2) is an efficient and ecofriendly catalyst for the one-pot synthesis of nitriles from aldehydes under solvent-free conditions under both conventional and microwave irradiation. Nitriles were obtained in good to excellent yields.
U. B. Patil, S. S. Shendage, J. M. Nagarkar, Synthesis, 2013, 45, 3295-3299.
An efficient cross-coupling reaction of aryl/het-aryl/benzyl halides with stable and easily workable sulfonyl hydrazides as thiol substitutes delivers unsymmetrical sulfides in the presence [DBU][HOAc] and CuI under microwave irradiation.
N. Singh, R. Singh, D. S. Raghuvanshi, K. N. Singh, Org. Lett., 2013, 15, 5874-5877.
An easy Pd-mediated oxidation of primary amines to imines followed by aniline addition enables an alkylation of anilines. The process is characterized by a high atom economy as ammonia is the only byproduct. The catalyst could be successfully recycled up to three times.
P. Linciano, M. Pizzetti, A. Porcheddu, M. Taddei, Synlett, 2013, 24, 2249-2254.
A reductive cyclization of o-nitrobenzylidene amines under microwave conditions in the presence of MoO2Cl2(dmf)2 as catalyst and Ph3P as reducing agent delivers 2-aryl-2H-indazoles in good yields.
A. H. Moustafa, C. C. Malakar, N. Aljaar, E. Merisor, J. Conrad, U. Beifuss, Synlett, 2013, 24, 1573-1577.
An efficient, microwave-assisted ligand-free and catalyst-free coupling of various nitroarenes and phenols produces nonsymmetrical diaryl ethers. The newly developed method is an ecofriendly and cost-effective approach to synthesize nonsymmetrical aryl ethers.
A. P. Sarkate, S. S. Bahekar, V. M. Wadhai, G. N. Ghandge, P. S. Wakte, D. B. Shinde, Synlett, 2013, 24, 1513-1516.
The Krapcho decarboxylation of alkyl malonate derivatives has been adapted to aqueous microwave conditions. For salt additives, a strong correlation was found between the pKa of the anion and the reaction rate, suggesting a straightforward base-catalyzed hydrolysis. Lithium sulfate gave the best results, obviating the need for DMSO as co-solvent.
J. D. Mason, S. S. Murphree, Synlett, 2013, 24, 1391-1394.
The key step in a new route for the construction of 2-aminoimidazolidines is an intramolecular microwave-assisted Staudinger/aza-Wittig cyclization of an in situ generated urea intermediate upon treatment with Bu3P or polymer-supported phosphine reagent. Furthermore, a useful one-pot Staudinger/aza-Wittig/Buchwald-Hartwig protocol leading to bicyclic guanidines has been elaborated.
R. Kumar, D. S. Ermolat'ev, E. V. Van der Eycken, J. Org. Chem., 2013, 78, 5737-5743.
N-heterocyclic carbene (NHC)-catalyzed C-C bond cleavage of carbohydrates as formaldehyde equivalents generates acyl anion intermediates for Stetter reaction via a retro-benzoin-type process. The renewable nature of carbohydrates, accessible from biomass, further highlights the practical potential of this fundamentally interesting catalytic activation.
J. Zhang, C. Xing, B. Tiwari, Y. R. Chi, J. Am. Chem. Soc., 2013, 135, 8113-8116.
An efficient microwave-accelerated method allows the conversion of inactive nitriles into 5-substituted 1H-tetrazoles in DMF.
H. Yoneyama, Y. Usami, S. Komeda, S. Harusawa, Synthesis, 2013, 45, 1051-1059.
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Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )