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
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.
A metal-free and eco-friendly coupling of readily available diaryliodonium salts and arenesulfinates in PEG-400 under microwave irradiation enables the preparation of various diaryl sulfones in high yields and short reaction times under mild conditions. Furthermore, the coupling of diaryliodonium with arenesulfinate salts with and without copper iodide provides a convenient access to various diaryl sulfones with high selectivity.
D. Kumar, V. Arun, M. Pilania, K. P. Chandra Shekar, Synlett, 2013, 24, 831-836.
In a new version of the Fischer indole synthesis, primary and secondary alcohols have been catalytically oxidized in the presence of phenylhydrazines and Lewis acids to give the corresponding indoles in one step. The use of alcohols instead of aldehydes or ketones broadens the scope of available starting materials and offers easy handling and safety.
A. Porcheddu, M. G. Mura, L. De Luca, M. Pizzetti, M. Taddei, Org. Lett., 2012, 14, 6112-6115.
Activation of the nitrile substrate by the Brønsted or Lewis acid catalyst is responsible for rate enhancement in azide-nitrile cycloaddition. Lewis acids such as Zn or Al salts perform in a similar manner, activating the nitrile moiety and leading to an open-chain intermediate that subsequently cyclizes to produce the tetrazole nucleus. The desired tetrazole structures were obtained in high yields within 3-10 min employing controlled microwave heating.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011, 133, 4465-4475.
Diverse alcohols were synthesized by metal-free coupling of diazoalkanes derived from p-toluenesulfonylhydrazones to water under reflux and microwave conditions, in high yields. In addition, this protocol was successfully applied in the synthesis of deuterium-labeled alcohols using deuterium oxide.
Á. García-Muñoz, A. I. Ortega-Arizmendi, M. A. García-Carrillo, E. Díaz, N. Gonzalez-Rivas, E. Cuevas-Yañez, Synthesis, 2012, 44, 2237-2242.
An efficient microwave-assisted, palladium-catalyzed hydroxylation converts aryl and heteroaryl chlorides to phenols in the presence of a weak base carbonate. The reaction tolerates ketone, aldehyde, ester, nitrile, or amide functionalities.
C.-W. Yu, G. S. Chen, C.-W. Huang, J.-W. Chern, Org. Lett., 2012, 14, 3688-3691.
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.
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