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
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.
A novel microwave-assisted, operationally simple, tandem bis-aldol reaction of
ketone with paraformaldehyde catalyzed by polystyrenesulfonic acid in aqueous
medium delivers 1,3-dioxanes in high yield.
V. Polshettiwar, R. S. Varma, J. Org. Chem.,
2007,
72, 7420-7422.
A highly enantioselective rearrangement of β-amino alcohols was realized by
using a catalytic amount of trifluoroacetic anhydride.
T.-X. Métro, D. G. Pardo, J. Cossy, J. Org. Chem.,
2007,
72, 6556-6561.
Acetals and ketals are readily deprotected under neutral conditions in the
presence of acetone and indium(III)
trifluoromethanesulfonate as catalyst at room temperature or mild microwave
heating conditions to give the corresponding aldehydes and ketones in good to
excellent yields.
B. T. Gregg, K. C. Golden, J. F. Quinn, J. Org. Chem., 2007,
72, 5890-5893.
Palladium-phosphinous acids catalyze the microwave-assisted conjugate
addition of arylsiloxanes to a wide range of α,β-unsaturated substrates in water. The
described procedure eliminates the need for stoichiometric additives and an
excess of arylsiloxane, and does not require an inert atmosphere.
R. Lerebours, C. Wolf, Org. Lett., 2007,
9, 2737-2740.
Gold N-heterocyclic carbene complexes, in conjunction with a
silver salt, were found to efficiently catalyze the rearrangement of allylic
acetates under both conventional and microwave-assisted heating. The steric hindrance of
the ligand bound to gold was found crucial as
only extremely bulky ligands permitted the isomerization.
N. Marion, R. Gealageas, S. P. Nolan, Org. Lett., 2007,
9, 2653-2656.
Hoveyda-Grubbs catalyst in combination with BF3ˇOEt2 efficiently promotes
tandem cross metathesis intramolecular aza-Michael reaction between enones and
unsaturated carbamates resulting in the creation of β-amino carbonyl units. The
use of microwave irradiation dramatically accelerates the process, but also inverts the
stereoselectivity in the addition process.
S. Fustero, D. Jiménez, M. Sánchez-Roselló, C. del Pozo, J. Am. Chem. Soc., 2007,
129, 6700-6701.
An effective and mild microwave-assisted route to 2-substituted benzofurans
directly from carboxylic acids allows the preparation of
α-alkyl-2-benzofuranmethanamines from N-protected α-amino acids without
racemization in good yields.
L. De Luca, G. Giacomelli, G. Nieddu, J. Org. Chem., 2007,
72, 3955-3957.
A Lewis acid catalyzed and solvent free procedure for the preparation of imides
from the corresponding anhydrides uses TaCl5-silica gel as Lewis acid
under microwave irradiation.
S. Chandrasekhar, M. Takhi, G. Uma, Tetrahedron Lett., 1997,
38, 8089-8092.
Please cite and link this page as follows:
Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )
Saturday, 04-Jul-2009 08:23:57 CEST
