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 convenient Ni-catalyzed C-N bond formation enables the synthesis
of various benzimidazoles in excellent yields from various 2-haloanilines,
aldehydes, and ammonia as nitrogen
source.
F. Ke, P. Zhang, Y. Xu, X. Lin, J. Lin, C. Lin, J. Xu, Synlett, 2018, 29,
2722-2726.
A catalyst-free amination of 2-mercaptobenzoxazoles on water under microwave
irradiation provides 2-aminobenzoxazoles in good yields via direct amination.
Key benefits of this process include an on-water reaction, short reaction time,
being scalable and catalyst-free, and use of 2-mercaptobenzoxazoles as an
inexpensive starting material.
T. Tankam, J. Srisa, M. Sukwattanasinitt, S. Wacharasindhu, J. Org. Chem., 2018, 83,
11936-11943.
An AgOTf-catalyzed reaction of β-(2-Aminophenyl)-α,β-ynones provides
3-unsubstituted 2-acylindoles in good yields under microwave heating. The use of
Cu(OTf)2 as a catalyst resulted in a similar reaction outcome, albeit with a lower
efficiency.
N. D. Rode, I. Abdalghani, A. Arcadi, M. Aschi, M. Chiarini, F. Marinelli, J. Org. Chem., 2018, 83,
6354-6362.
Formation of enamino ketones from 1-(2-hydroxyphenyl)ethanone derivatives under
microwave heating followed by cyclization using T3P® provides 4H-chromene-4-ones
in short reaction times and high purity.
C. Balakrishna, V. Kandula, R. Gudipati, S. Yennam, P. U. Devi, M. Behera,
Synlett, 2018, 29, 1087-1091.
A practical and general microwave-mediated Biginelli cyclocondensation of
guanidine with aldehydes and β-dicarbonyl compounds provides functionalized
2-amino-3,4-dihydropyrimidines in good yields, with short reaction times and a
simple workup. The scope is considerably wider than that of similar reactions
carried out under conventional heating.
F. Felluga, F. Benedetti, F. Berti, S. Drioli, G. Regini,
Synlett, 2018, 29, 986-992.
DABCO promotes an efficient, solvent-free, and eco-friendly domino reaction of
various β,γ-unsaturated α-ketocarbonyls with 5/6-membered cyclic sulfamidate
imines in neat conditions under MW irradiation to provide densely functionalized
picolinates in short reaction times.
S. Biswas, D. Majee, S. Guin, S. Samanta, J. Org. Chem.,
2017, 82, 10928-10938.
A transition-metal-free synthesis of a series of primary arylamines from
potassium aryltrifluoroborates and phenylboronic acids uses hydroxylamine-O-sulfonic
acid as a mild, inexpensive source of nitrogen in cooperation with aqueous
sodium hydroxide in acetonitrile. Both a sonication and a microwave-assisted
method were developed.
D. Kuik, J. A. McCubbin, G. K. Tranmer, Synthesis, 2017,
49, 2555-2561.
Polyphosphoric acid (PPA) esters promote a microwave-assisted procedure for
the synthesis of 5- to 7-membered cyclic iminoethers from amido alcohols.
2-Aryl-2-oxazolines and 5,6-dihydro-4H-1,3-oxazines were efficiently
prepared using ethyl polyphosphate/CHCl3 in very good yields and
short reaction time. Trimethylsilyl polyphosphate under solvent-free conditions
enables the synthesis of 4,5,6,7-tetrahydro-1,3-oxazepines.
M. C. Mollo, L. R. Orelli, Org. Lett.,
2016, 18, 6116-6119.
A microwave-assisted flow generation of primary ketenes by thermal decomposition
of α-diazoketones at high temperature followed by in situ reaction with amines
and imines provides a number of amides and trans β-lactams, respectively,
in very good yields.
B. Musio, F. Mariani, E. P. Śliwiński, M. A. Kabeshov, H. Odajima, S. V. Ley, Synthesis, 2016,
48, 3515-3526.
A microwave-assisted flow generation of primary ketenes by thermal decomposition
of α-diazoketones at high temperature followed by in situ reaction with amines
and imines provides a number of amides and trans β-lactams, respectively,
in very good yields.
B. Musio, F. Mariani, E. P. Śliwiński, M. A. Kabeshov, H. Odajima, S. V. Ley, Synthesis, 2016,
48, 3515-3526.
In a palladium catalyzed Negishi-type α-arylation of sulfones and sulfonamides
with a broad range of aryl bromides, the substrates are selectively metalated in
situ with tmp·ZnCl·LiCl base and cross-coupled in the presence of a catalyst
system that is generated from Pd(dba)2 and XPhos.
T. Knauber, J. Tucker, J. Org. Chem.,
2016,
81, 5636-5648.
An acceptorless coupling of o-aminobenzamides with methanol has been
accomplished in the presence of the metal-ligand bifunctional catalyst [Cp*Ir(2,2′-bpyO)(H2O)]
to provide quinazolinones in good yields.
F. Li, L. Lu, P. Liu, Org. Lett.,
2016, 18, 2580-2583.
Heck isomerization of aryl bromides and allyl alcohols provides 3-arylpropanals,
that can readily be transformed into 3-arylmethylindoles by Fischer indole
synthesis in a consecutive three-component fashion in good yields. This sequence
can be expanded to a four-component Heck isomerization-Fischer
indolization-alkylation (HIFIA) synthesis.
J. Panther, T. J. J. Müller,
Synthesis, 2016, 48, 974-986.
A Schiff’s base complex nickel catalyst (Ni-C) enables a highly efficient
one-pot microwave-assisted synthesis of 2,4,5-trisubstituted imidazoles in
excellent yields from aldehydes, benzil, and ammonium acetate. The catalyst
could be easily recovered by simple filtration and reused.
T. S. Chundawat, N. Sharma, P. Kumari, S. Bhagat,
Synlett, 2016, 27, 404-408.
A New Simplified Protocol for Copper(I) Alkyne-Azide Cycloaddition Reactions
Using Low Substoichiometric Amounts of Copper(II) Precatalysts in Methanol
B. R. Buckley, M. M. P. Figueres, A. N. Khan, H. Heaney,
Synlett, 2016, 27, 51-56.
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