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 this novel technique.
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?
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
C. O. Kappe, "Controlled Microwave Heating in Modern Organic Synthesis", Angew. Chem. Int. Ed. 2004, 43, 6250. DOI
Books
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
Electronically deactivated and/or sterically hindered substrates undergo the
Newman-Kwart rearrangement (NKR) at around 300°C using modern microwave
technology. In addition, several previously reported difficult examples were
re-investigated, and the NKR under the reported conditions was found to be a
reliable and high yielding reaction.
J. D. Moseley, P. Lenden, Tetrahedron, 2007,
63, 4120-4125.
Microwave technology has proven to be ideal for investigating the Newman-Kwart rearrangement (NKR)
at high
temperatures and facilitated the confirmation of many aspects of
this valuable reaction. Comparisons between thermal and microwave results
indicate no evidence of a significant microwave effect.
J. D. Moseley, R. F. Sankey, O. N. Tang, J. P. Gilday, Tetrahedron, 2006,
62, 4685-4689.
The direct conversion of various amides to isoquinoline and β-carboline
derivatives via mild electrophilic amide activation, with
trifluoromethanesulfonic anhydride in the presence of 2-chloropyridine followed
by cyclodehydration upon warming provides the desired products with short
overall reaction times.
M. Movassaghi, M. D. Hill, Org. Lett., 2008,
10, 3485-3488.
An experimentally simple Microwave-assisted reductive alkylation of methyl
carbamate with a range of aldehydes provides, after basic work-up, structurally
diverse primary amines. This method is particularly amenable to high-throughput
synthesis.
F. Lehmann, M. Scobie, Synthesis, 2008,
1679-1681.
An easy and handy synthesis of sulfonamides directly from sulfonic acids or its
sodium salts is performed under microwave irradiation, has shown a good
functional group tolerance, and is high yielding.
L. De Luca, G. Giacomelli, J. Org. Chem., 2008,
73, 3967-3969.
p-Toluenesulfonic acid (PTSA) in ethanol was used as a mild acid catalyst
for the annulation of various functionalized diarylalkynes under microwave
irradiation. This metal-free process allowed the synthesis of various
3-aryl-substituted isocoumarins in good yields.
G. Le Bras, A. Hamze, S. Messaoudi, O. Provot, P.-B. Le Calvez, J.-D. Brion, M.
Alami, Synthesis, 2008,
1607-1611.
A versatile one-pot domino acylation annulation reaction of 2-bromoanilines with
acyl chlorides in the presence of Cs2CO3, catalytic CuI,
and 1,10-phenanthroline under microwave conditions was applied to the synthesis
of benzoxazoles. These copper-catalyzed approaches complement existing
strategies for benzoxazole synthesis, which typically utilize 2-aminopheonls as
precursors.
R. D. Viirre, G. Evindar, R. A. Batey, J. Org. Chem., 2008,
73, 3452-3459.
A novel, simple and convenient thionation protocol for carbonyl compounds with
the system PSCl3/H2O/Et3N allows a clean,
rapid, and efficient synthesis of a variety of thiocarbonyl compounds such as
thioamides, thiolactams, thioketones, thioxanthones and thioacridone under
solventless condition with microwave irradiation.
U. Pathak, L. K. Pandey, R. Tank, J. Org. Chem., 2008,
73, 2890-2893.
Fluoride-free cross-coupling reactions of alkenyltrialkoxysilanes with aryl
iodides, bromides, and chlorides are performed under ligand-free conditions with
low Pd loadings on water using sodium hydroxide as activator and tetra-n-butylammonium
bromide as additive at 120°C under conventional or microwave heating.
E. Alacid, C. Nájera, J. Org. Chem., 2008,
73, 2315-2322.
An environmentally friendly and highly efficient procedure gives
2,4-disubstituted quinoline derivatives by a simple alkynylation-cyclization
reaction of 2-aminoaryl ketones with phenylacetylenes in the presence of
indium(III) trifluoromethanesulfonate In(OTf)3 under microwave
irradiation and solvent-free conditions. The catalyst can be reused.
K. C. Lekhok, D. Prajapati, R. C. Boruah, Synlett, 2008,
655-658.
The consecutive Sonogashira coupling of acid chlorides with terminal alkynes,
followed by 1,3-dipolar cycloaddition under dielectric heating of in situ
generated nitrile oxides from hydroximinoyl chlorides furnishes isoxazoles in
moderate to good yields in the sense of a one-pot three-component reaction.
B. Willy, F. Rominger, T. J. J. Müller, Synthesis, 2008,
293-303.
The reaction of esters with hydroxylamine in the presence of a base under
microwave activation provides hydroxamic acids in good yields and purity. The
method has been successfully applied to enantiomerically pure esters without
loss of stereochemical integrity.
A. Massaro, A. Mordini, G. Reginato, F. Russo, M. Taddei, Synthesis, 2007,
3201-3204.
Synthesis of oxazolidin-2-ones derivatives was carried out starting from urea
and ethanolamine reagents using microwave irradiation in a chemical paste medium
in which a catalytic amount of nitromethane absorbs the microwaves and generates
hot spots.
G. Bratulescu, Synthesis, 2007,
3111-3112.
Tri- or tetrasubstituted pyridines are prepared by microwave irradiation of
ethyl β-aminocrotonate and various alkynones in a single synthetic step and with
total control of regiochemistry. This new one-pot Bohlmann-Rahtz procedure
conducted at 170°C gives superior yields to similar experiments conducted using
conductive-heating techniques in a sealed tube.
M. C. Bagley, R. Lunn, X. Xiong, Tetrahedron Lett., 2002,
43, 8331-8334.
Please cite and link this page as follows:
Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )
