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
A convenient and chemoselective method for deoxygenation of pyridine N-oxide
derivatives by transfer oxidation of triethylamine under microwave irradiation
is catalysed by [Pd(OAc)2]/dppf.
J. A. Fuentes, M. L. Clarke, Synlett, 2008,
2579-2582.
A highly efficient catalyst-free, thermally induced cycloisomerization allows
the synthesis of indolizinones from readily available tertiary propargylic
alcohols. In addition, this transformation was found to be further expedited by
microwave irradiation.
I. Kim, J. Choi, S. Lee, G. H. Lee, Synlett, 2008, 2334-2338.
Microwave irradiation significantly enhances the rate of formation of
1,4-disubstituted 1,2,3-triazoles from alkynes and in situ generated azides.
Azides are derived from an efficient one-pot azidation of anilines with the
reagent combination t-BuONO and TMSN3.
A. D. Moorhouse, J. E. Moses, Synlett, 2008,
2089-2092.
An efficient and effective microwave-assisted cross-coupling of terminal
alkynes with various aryl chlorides including sterically hindered substrates
proceeds fast and generally gives coupled products in very good yields. The
conditions were extended successfully to Suzuki coupling, Buchwald-Hartwig
amination, and the Heck coupling of aryl chlorides.
H. Huang, H. Liu, H. Jiang, K. Chen, J. Org. Chem., 2008,
73, 6037-6040.
The reaction of (2-aminobenzyl) triphenylphosphonium bromide with aromatic
aldehydes or α,β-unsaturated aldehydes under microwave-assisted conditions
allows the synthesis of 2-substituted indoles in high yields in a one-pot
reaction.
G. A. Kraus, H. Guo, Org. Lett.,
2008,
10, 3061-3063.
Addition of sulfonamides to alkenes and conjugated dienes can be carried out
using a low catalytic amount of (triphenyl phosphite)gold(I) chloride and silver
triflate under thermal or microwave conditions and at r.t. in the case of
dienes. Terminal alkenes undergo regioselective hydroamination at the internal
carbon atom and dienes at the less substituted double bond.
X. Giner, C. Nájera, Org. Lett.,
2008,
10, 2919-2922.
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.
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Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )
