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
An efficient and simple protocol for phosphine-free Heck reactions in water in
the presence of a Pd(L-proline)2 complex as the catalyst under
controlled microwave irradiation conditions is versatile and provides excellent
yields of products in short reaction times. The reaction system minimizes costs,
operational hazards and environmental pollution.
B. K. Allam, K. N. Singh, Synthesis, 2011,
1125-1131.
Microwave heating enables a Borrowing Hydrogen strategy to form C-N bonds from
alcohols and amines, removes the need for solvent and reduces the reaction times,
while the results are comparable with those using thermal heating.
A. J. A. Watson, A. C. Maxwell, J. M. J. Williams, J. Org. Chem., 2011,
76, 2328-2331.
An organocatalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide,
generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and
trimethylsilyl chloride, enables the formation of tetrazoles by cycloaddition of
sodium azide with organic nitriles under neutral conditions and microwave
heating. The organocatalyst accelerates the azide-nitrile coupling by activating
the nitrile substrate.
D. Cantillo, B. Gutmann, C. O. Kappe, J. Am. Chem. Soc., 2011,
133, 4465-4475.
High-speed and scalable nickel-catalyzed cross-coupling of arylboronic acids
with aryl carbamates and sulfamates is achieved by using sealed-vessel microwave
processing.
M. Baghbanzadeh, C. Pilger, C. O. Kappe, J. Org. Chem., 2011,
76, 1507-1510.
An efficient and simple method enables the N-alkylation of aromatic cyclic
imides using cesium carbonate as the base in anhydrous N,N-dimethylformamide
at low temperatures (20-70˚C). The employment of microwave irradiation presents
noteworthy advantages over conventional heating. The method is compatible with
base labile functional groups.
M. I. Escudero, L. D. Kremenchuzky, I. A. Perillo, H. Cerecetto, M. M. Blanco, Synthesis, 2011,
571-576.
An eco-compatible method for the formation of tert-butyl ethers of
alcohols and phenols is performed in solvent-free conditions at room temperature
using catalytic amount of Er(OTf)3. The catalyst is easily recovered
and reused several times without loss of activity. In addition, the tert-butyl
group is removed very quickly from alcohols and phenols in methanol in the
presence of Er(OTf)3 using MW irradiation.
A. Procopio, P. Costanzo, M. Curini, M. Nardi, M. Oliverio, R. Paonessa, Synthesis, 2011,
73-78.
Functionalized organozinc reagents readily react regioselectively with various
aryldiazonium salts to yield polyfunctional indoles after heating with microwave
irradiation. This new organometallic variation of the Fischer indole synthesis
tolerates a wide range of functional groups and can be readily scaled up.
Z..-G. Zhang, B. A. Haag, J.-S. Li, P. Knochel, Synthesis, 2011,
23-29.
A series of 2,4-disubstituted quinolines were easily prepared through a
one-pot reaction of structurally diverse 2-aminoaryl ketones with various
arylacetylenes in the presence of K5CoW12O40 •
3 H2O as a reusable and environmentally benign catalyst under
microwave irradiation and solvent-free conditions.
I. Mohammadpoor-Baltork, S. Tangestaninejad, M. Moghadam, V. Mirkhani, S.
Anvar, A. Mirjafari, Synlett, 2010,
3104-3112.
A Pd(0)-catalyzed cross-coupling reaction of diazirines with aryl halides under
microwave irradiation affords substituted olefins in good yields via a migratory
insertion of a Pd carbene intermediate.
H. Jiang, H. Huang, H. Cao, C. Qi, Org. Lett., 2010,
12, 5561-5563.
A microwave-assisted, one-pot, three-step Sonogashira
cross-coupling-desilylation-cycloaddition sequence enables a convenient
preparation of 1,4-disubstituted 1,2,3-triazoles starting from a range of aryl
halides, aroyl chlorides, ethynyltrimethylsilane, and azides.
F. Friscourt, G.-J. Boons, Org. Lett., 2010,
12, 4936-4939.
A mild, gold(I)-catalyzed cycloisomerization of β-allenylhydrazones provides an
efficient access to multisubstituted N-aminopyrroles in good to excellent
yields with short reaction times through a selective intramolecular 1,2-alkyl or
-aryl migration. This intramolecular cyclization can be applied either to alkyl-
or aryl-substituted allenes.
E. Benedetti, G. Lemière, L.-L. Chapellet, A. Penoni, G. Palmisano, M. Malacria,
J.-P. Goddard, L. Fensterband, Org. Lett., 2010,
12, 4396-4399.
An efficient and practical molybdenum-mediated carbonylation of aryl and
heteroaryl halides with a variety of nucleophiles using microwave irradiation
offers a wide scope and proceeds in good to excellent yields.
B. Roberts, D. Liptrot, L. Alcaraz, T. Luker, M. J. Stocks, Org. Lett., 2010,
12, 4280-4283.
Microwave-assisted Bischler-Napieralski or Pictet-Spengler reactions allowed the
production of substituted isoquinoline libraries. The generated
dihydroisoquinolines and tetrahydroisoquinolines could be oxidized to their
corresponding isoquinoline analogues. A more practical and efficient route to
C1- and C4-substituted isoquinolines involves the preparation and activation of
isoquinolin-1(2H)-ones.
E. Awuah, A. Capretta, J. Org. Chem., 2010,
75, 5627-5634.
N-Phenacylpyridinium bromides, which were prepared in situ from the
addition of pyridines to α-bromoketones, undergo nucleophilic addition of
ammonium acetate under microwave irradiation and solvent-free conditions to
afford the corresponding imidazo[1,2-a]pyridines in excellent yields.
M. Adib, A. Mohamadi, E. Sheikhi, S. Ansari, H. R. Bijanzadeh, Synlett, 2010,
1606-1608.
Borono-Mannich reactions can be performed in solvent-free conditions under
microwave irradition with short reaction time. Full conversion of the starting
materials towards the expected product was achieved, starting from
stoichiometric quantities of reactants, avoiding column chromatography. No
purification step other than an aqueous washing was required.
P. Nun, J. Martinez, F. Lamaty, Synthesis, 2010,
2063-2068.
A concise, stereoselective synthesis of functionalized tetrahydrofuranols
involves heating of readily available chloropolyols in water. These reactions
are operationally straightforward and chemoselective for the formation of
tetrahydrofurans, obviating the need for complicated protecting group strategies.
A short asymmetric synthesis of the natural product (+)-goniothalesdiol is
demonstrated.
B. Kang, S. Chang, S. Decker, R. Britton, Org. Lett., 2010,
12, 1716-1719.
Please cite and link this page as follows:
Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )
