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
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
Primary and secondary alcohols have been converted into 2-amino-1,3-thiazoles
under microwave irradiation, employing trichloroisocyanuric acid (TCCA) as a
dual oxidant and chlorine source, TEMPO as a co-oxidant, and thiourea. While
primary alcohols required a two-stage, one-pot procedure, secondary alcohols
underwent a single-stage, one-pot conversion process.
P. Macías-Benítez, A. Sierra-Padilla, F. M. Guerra, F. J. Moreno-Dorado, J. Org. Chem., 2024, 89,
4628-4645.
A double aza-Michael addition of anilines to water-insoluble divinyl sulfones
on the surface of water provides solid cyclic β-amino sulfones as easily
separable products in excellent yields upon microwave irradiation at 150°C for
10 min. This atom-efficient method converts a broad range of amines and offers
good functional group tolerance. Acyclic β-amino sulfones can also be
synthesized.
S. Saha, A. Chatterjee, M. Banerjee, J. Org. Chem., 2023, 88,
15358-15366.
2-Substituted aryl and alkyl benzimidazole derivative were synthesized using
microwave. This method is more beneficial, in respect of yield (increases up to
10 to 50%) and time (96 to 98% was reduced) than conventional heating. The use
of o-phenylenediamine dihydrochloride gave reduced colour impurities,
homogenous mixing and reduced time for completion of reaction.
R. Dubey, N. S. H. N. Moorthy, Chem. Pharm. Bull, 2007,
55, 115-117.
A mild, green, and convenient one-pot carbon-chain extension of carboxylic acids
with the assistance of microwaves and lithium chloride avoids the use of
corrosive reagents, is tremendously faster than previously methods, and was free
of configurational isomerization. Notably, LiCl played a dual role in the
Krapcho decarboxylation and subsequent ester hydrolysis under neutral conditions.
C. Wang, J. Su, Y. Li, S. Gao, X. Huo, B. Yi, G. Zhao, Synlett, 2023,
34,
1033-1036.
A series of 1-alkoxy-3-methyl- and 3,4-dimethyl-3-phospholene 1-oxides, as well
as 1-alkoxy-3-methylphospholane 1-oxides were prepared in good yields by a
microwave-assisted and [bmim][PF6]-catalyzed transesterification of
the corresponding methyl or ethyl esters.
N. Harsági, N. Z. Kiss, L. Drahos, G. Keglevich, Synthesis, 2022, 54,
3899-3905.
Synthesis of 2-Alkoxy-Substituted Thiophenes, 1,3-Thiazoles, and Related S-Heterocycles via Lawesson's Reagent-Mediated Cyclization under Microwave
Irradiation: Applications for Liquid Crystal Synthesis
A. A. Kiryanov, P. Sampson, A. J. Seed, J. Org. Chem., 2001,
66, 7925-7929.
[IPrH][F(HF)2] is a highly selective and soluble reagent for a
microwave-assisted fluorination of various organic substrates. The scope of
substrates includes benzyl bromides, iodides, chlorides, aliphatic halides,
tosylates, mesylates, α-haloketones, a silyl chloride, acyl and sulfuryl
chlorides, and a nitroarene. The reagent can be regenerated using hydrofluoric
acid without organic solvents.
B. Alič, J. Petrovčič, J. Jelen, G. Tavčar, J. Iskra, J. Org. Chem., 2022, 87,
5987-5993.
A silicon nanoarray palladium catalyst mediates a hydrogenolysis of
iodoarenes under microwave irradiation in the presence of triethanolamine as the
sacrificial reductant. The reductive deiodination proceeded under an aerobic
atmosphere affording the corresponding hydrogen-substituted arenes in high
yields. No reaction occurred in the absence of microwaves.
Y. Matsukawa, Y. M. A. Yamada, Synlett, 2022,
33,
777-780.
Rapid Homogeneous-Phase Sonogashira Coupling Reactions Using Controlled
Microwave Heating
M. Erdélyi, A. Gogoll, J. Org. Chem., 2001,
66, 4165-4169.
FeCl3 catalyzes a solvent-free sulfonylation of arenes under
microwave irradiation. With more reactive and/or nonvolatile substrates (anisole,
xylenes, mesitylene) a short reaction time at constant MW power without control
of the temperature was used. With less reactive and/or low-boiling reagents (benzene,
toluene, halobenzenes), the MW power was controlled. A nonthermal effect was not
observed.
J. Marquié, A. Laporterie, J. Dubac, N. Roques, J.-R. Desmurs, J. Org. Chem., 2001,
66, 421-425.
The use of a magnetically recoverable palladium nanocatalyst supported on a
green biochar enables an efficient palladium-catalyzed tandem reaction for the
one-pot synthesis of 9H-carbazoles from inexpensive anilines and
1,2-dihaloarenes under microwave irradiation. The method shows a drastic
reduction in reaction times and excellent compatibility with different
functional groups.
H. S. Steingruber, P. Mendioroz, M. A. Volpe, D. C. Gerbino, Synthesis, 2021, 53,
2212-2218.
A highly efficient microwave-assisted Cu(I)-catalyzed
cross-A3-coupling/decarboxylative coupling of two different amines, formaldehyde,
and propiolic acid provides unsymmetric 1,4-diamino-2-butynes through a domino
process in good yields with high chemoselectivity.
X. Xu, H. Feng, E. V. Van der Eycken, J. Org. Chem., 2021, 86,
14036-14043.
An efficient palladium-catalyzed reaction of N-propargyl oxazolidines
provides 4-substituted isoquinolines under microwave irradiation through a
sequential palladium-catalyzed reductive cyclization/ring-opening/aromatization
cascade via C-O and C-N bond cleavages of the oxazolidine ring.
X. Xu, H. Feng, E. V. Van der Eycken, Org. Lett., 2021, 23,
6578-6582.
Aryl and vinyl nitriles have been prepared in very high yields from the
corresponding bromides using palladium-catalyzed reactions under microwave
irradiation. Furthermore, flash heating was used successfully for the conversion
of these nitriles into aryl and vinyl tetrazoles by cycloaddition reactions.
One-pot transformation of aryl halides directly to the aryl tetrazoles could
also be accomplished.
M. Alterman, A. Hallberg, J. Org. Chem., 2000,
65, 7984-7989.
5-hydroxymethyl furfural is a biomass-derived commodity chemical that is ideal to
prepare next-generation value-added products. Decarboxylative cross-couplings
enable an efficient access to 2,5-diaryl furans. A key finding was that the
presence of the hydroxymethyl handle enhances the yields of the
first palladium-catalyzed decarboxylative cross-coupling reaction.
F. Chacón-Huete, J. D. Lasso, P. Szavay, J. Covone, P. Forgione, J. Org. Chem., 2021, 86,
515-524.
Environmentally Friendly Nafion-Mediated Friedländer Quinoline Synthesis
under Microwave Irradiation: Application to One-Pot Synthesis of Substituted
Quinolinyl Chalcones
C.-K. Chan, C.-Y. Lai, C.-C. Wang, Synthesis, 2020, 52,
1779-1794.
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