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 |
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Microwaves in Organic Synthesis André Loupy Hardcover, 499 Pages |
Recent Literature
Hoveyda-Grubbs catalyst in combination with BF3·OEt2 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.
A series of primary alcohols and aldehydes were treated with iodine in ammonia
water under microwave irradiation to give the intermediate nitriles, which
without isolation underwent [2 + 3] cycloadditions with dicyandiamide and sodium
azide to afford the corresponding triazines and tetrazoles in high yields.
J.-J. Shie, J.-M. Fang, J. Org. Chem., 2007,
72, 3141-3144.
Zirconium(IV)-catalyzed exchange processes of dialkyl carbonates and carbamates
in the presence of amines gave carbamates and ureas using 2-hydroxypyridine (HYP)
and 4-methyl-2-hydroxyquinoline (MeHYQ) as catalytic additives, respectively. A
microwave acceleration effect was observed in Zr(IV)-catalyzed carbamate-urea
exchange.
C. Han, J. A. Porco, Jr, Org. Lett., 2007,
9, 1517-1520.
A one-pot reaction between nitriles, hydroxylamine and Meldrum’s acids under
microwave irradiation and solvent-free conditions gives 3,5-disubstituted
1,2,4-oxadiazoles in good to excellent yields.
M. Adib, M. Mahdavi, N. Mahmoodi, H. Pirelahi, H. R. Bijanzadeh, Synlett, 2006,
1765-1767.
The Gewald reaction of PEG-bound cyanoacetic ester, elemental sulfur, DIPEA
and carbonyl compounds carried out under microwave irradiation afforded
PEG-supported thiophenes, which were acylated and treated with 1% KCN in
methanol to give free thiophenes in good yields. This synthetic method is simple
and mild.
H. Zhang, G. Yang, J. Chen, Z. Chen, Synlett, 2004,
3055-3059.
Addition of Grignard reagents to pyridine N-oxides in THF at room
temperature and subsequent treatment with acetic anhydride at 120°C afforded
2-substituted pyridines in good yields. By exchanging acetic anhydride for DMF
in the second step, 2-substituted pyridine N-oxides were obtained,
enabling the synthesis of 2,6-disubstituted pyridines.
H. Andersson, F. Almqvist, R. Olsson, Org. Lett., 2007,
9, 1335-1337.
Lawesson’s reagent is an efficient promoter in the solvent-free
microwave-assisted synthesis of 2-substituted benzoxazoles and benzothiazoles
from carboxylic acids and 2-aminophenol or 2-aminothiophenol, respectively.
Various aromatic, heteroaromatic and aliphatic carboxylic acids react under the
conditions developed with good yields.
J. A. Seijas, M. P. Vázquez-Tato, M. R. Carballido-Reboredo, J.
Crecente-Campo, L. Romar-López, Synlett, 2007, 313-316.
Trapping of β,γ-alkynyl aldehydes, generated in situ by treatment of alkynyloxiranes with a
catalytic amount of Sc(OTf)3 or BF3·OEt2, by a variety of allyl nucleophiles affords homopropargylic
homoallylic alcohols in good yield and selectivity. Subsequent enyne metathesis
gives functionalized vinylcyclopentenols.
L. Wang, M. L. Maddess, M. Lautens, J. Org. Chem., 2007,
72, 1822-1825.
A novel and efficient synthesis of pyrimidine from β-formyl enamide involves
samarium chloride catalysed cyclisation of β-formyl enamides using urea as
source of ammonia under microwave irradiation.
M. G. Barthakur, M. Borthakur, P. Devi, C. J. Saikia, A. Saikia, U. Bora, A.
Chetia, R. C. Boruah, Synlett, 2007, 223-226
A very simple and efficient, microwave-assisted procedure is reported for the
synthesis of 1,3-diarylimidazolinium chlorides by cyclization of N,N′-diarylethylenediamines
dihydrochlorides with triethyl orthoformate.
A. Aidouni, A. Demonceau, L. Delaude, Synlett,
2006, 493-495.
N-Vinylpyridinium and -trialkylammonium tetrafluoroborate salts represent
a new class of electrophilic coupling partner for Pd(0)-catalyzed Suzuki
cross-coupling reactions with various boronic acids in high yields. The
crystalline, air-stable, and nonhygroscopic salts are easily prepared from
activated acetylenes and pyridinium or trialkylammonium tetrafluoroborates.
K. R. Buszek, N. Brown, Org. Lett., 2007,
9, 707-710.
The solid-state reaction between anilines and phenacyl bromides in the presence
of an equimolecular amount of sodium bicarbonate or a second equivalent of the
aniline followod by microwave irradiation provides a mild, general, and
environmentally friendly method for the synthesis of 2-arylindoles in good
overall yields.
V. Sridharan, S. Perumal, C. Avendaño, J. C. Menéndez, Synlett,
2006, 91-95.
A regioselective one-pot synthesis of 2-alkyl-3,4-dihydro-3-oxo-2H-1,4-benzoxazines
under microwave heating starts from commercially available 2-aminophenols.
Base-mediated regioselective O-alkylation with 2-bromoalkanoates gives
acyclic intermediates. A subsequent intramolecular amidation reaction furnishes
the desired products in good yields.
W.-M. Dai, X. Wang, C. Ma, Tetrahedron, 2005,
61, 6879-6885.
A generally applicable method for the introduction of gaseous hydrogen into a
sealed reaction system under microwave irradiation allows the hydrogenation of
various substrates in short reaction times with moderate temperatures between 80
°C and 100 °C with 50 psi of hydrogen.
G. S. Vanier, Synlett, 2007, 131-135.
Please cite and link this page as follows:
Microwave Synthesis ( URL: http://www.organic-chemistry.org/topics/microwave-synthesis.shtm )
Saturday, 10-May-2008 01:35:03 CEST
