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
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
André Loupy
Hardcover, 499 Pages
First Edition, November 2002
ISBN: 3-527-30514-9 - Wiley-VCH
Recent Literature
A palladium complex of
1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane is an effective
catalyst for a sequential microwave-assisted Sonogashira and carbonylative
annulation reaction to give substituted flavones.
E. Awuah, A. Capretta, Org. Lett., 2009,
11, 3210-3213.
A domino alkylation-cyclization reaction of propargyl bromides with thioureas
and thiopyrimidinones allows the synthesis of 2-aminothiazoles and
5H-thiazolo[3,2-a]pyrimidin-5-ones, respectively. Domino reactions were
performed under microwave irradiation leading to desired compounds in a few
minutes and high yields.
D. Castagnolo, M. Pagano, M. Bernardini, M. Botta, Synlett, 2009,
2093-2096.
A rapid and convenient free-radical-based synthesis of functionalized
quinazolines relies on microwave-promoted reactions of O-phenyl oximes
with aldehydes in the presence of ZnCl2. The method worked well with
alkyl, aryl, and heterocyclic aldehydes and for a variety of substituents in the
benzenic part of the molecule.
F. Portela-Cubillo, J. S. Scott, J. C. Walton, J. Org. Chem., 2009,
74, 4934-4942.
Starting from 1,2-diketones and urotropine in the presence of ammonium acetate,
a simple and efficient solventless microwave-assisted enabled the synthesis of
4,5-disubstituted imidazoles.
G. Bratulescu, Synthesis, 2009,
2319-2320.
Alkylthiazolium-based ionic liquids, which can be synthesized under green
conditions, and triethylamine have been found to catalyze efficiently the
intramolecular Stetter reaction, giving excellent yields within very short
reaction times using solvent-free microwave activation conditions.
A. Aupoix, G. Vo-Thanh, Synlett, 2009,
1915-1920.
Addition of amide enolates to acylsilanes generates β-silyloxy homoenolates by
undergoing a 1,2-Brook rearrangement. These unique nucleophiles formed in situ
can then undergo addition to alkyl halides, aldehydes, ketones, and imines.
γ-Amino-β-hydroxy amide products derived from a diastereoselective addition to
N-diphenylphosphinyl imines can be efficiently converted to γ-lactams.
R. B. Lettan, II, C. V. Galliford, C. C. Woodward, K. A. Scheidt, J. Am. Chem. Soc., 2009,
131, 8805-8814.
5-Substituted tetrazoles were prepared in very good yields and short reaction
times by treatment of nitriles with sodium azide and triethylammonium chloride
in nitrobenzene in a microwave reactor. Even sterically hindered tetrazoles, as
well as those deactivated by electron-donating groups, can be prepared.
J. Roh, T. V. Artamonova, K. Vávrová, G. I. Koldobskii, A. Hrabálek, Synthesis, 2009,
2175-2178.
A very fast, microwave-assisted formation of carboxylic esters via reaction of carboxylic acids with O-alkylisoureas
derived from primary and secondary alcohols proceeds in good yields with clean
inversion of configuration where appropriate.
A. Chighine, S. Crosignani, M.-C. Arnal, M. Bradley, B. Linclau, J. Org. Chem., 2009,
74, 4638-4641.
An effective protocol allows the smooth protodecarboxylation of diversely
functionalized aromatic carboxylic acids within 5-15 min under microwave
irradiation. In the presence of an inexpensive catalyst generated in situ from
copper(I) oxide and 1,10-phenanthroline, even nonactivated benzoates were
converted in high yields.
L. J. Goossen, F. Manjolinho, B. A. Khan, N. Rodríguez, J. Org. Chem., 2009,
74, 2620-2623.
A microwave-assisted, chemoselective and efficient method for the cleavage of
silyl ethers is catalyzed by Selectfluor. A wide range of TBDMS-, TIPS-, and
TBDPS-protected alkyl silyl ethers can be chemoselectively cleaved in high yield
in the presence of aryl silyl ethers. In addition, the transetherification and
etherification of benzylic hydroxy groups in alcoholic solvents is observed.
S. T. A. Shah, S. Singh, P. J. Guiry, J. Org. Chem., 2009,
74, 2179-2182.
Ketones can efficiently be reduced to the corresponding methylene compound using
the convenient and inexpensive combination of PMHS and FeCl3.
C. Dal Zotto, D. Virieux, J.-M. Campagne, Synlett, 2009, 276-278
A rhodium(II)-catalyzed reaction of stable and readily available 1-sulfonyl
triazoles with nitriles gives the corresponding imidazoles in good to excellent
yields via rhodium iminocarbenoids intermediates.
T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan, V. V. Fokin, J. Am. Chem. Soc., 2008,
130, 14972-14974.
A one-pot synthesis of substituted pyridines via a domino cyclization-oxidative
aromatization approach is based on the use of a new bifunctional noble
metal-solid acid catalyst, Pd/C/K-10 montmorillonite and microwave irradiation.
The cyclization readily takes place on the strong solid acid while palladium
dehydrogenates the dihydropyridine intermediate.
O. De Paolis, J. Baffoe, S. M. Landge, B. Török, Synthesis, 2008,
3423-3428.
Various polyfunctional aryl and heteroaryl zinc compounds were
efficiently prepared in THF via direct zincation using (tmp)2Znˇ2MgCl2ˇ2LiCl
and microwave irradiation. Ester and cyano functions as well as ketones are
tolerated. The resulting bis-organo
zinc species undergo a number of coupling reactions leading to highly
functionalized products in very good yields.
S. Wunderlich, P. Knochel, Org. Lett.,
2008,
10, 4705-4707.
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