The Journal of Organic Chemistry
Article
that affect microwave enhancement are very complex and
appear to be a delicate balance between microwave power,
thermal properties of solution, and convective heat flow. This is
evident in the power-dependent studies, which show that when
we increase the power by changing the concentration, we
actually get less reactivity.
and that they arise from selective heating processes that arise
from the unique manner in which microwaves interact with
molecules in solution. The magnitude of the effects may be
regarded as modest, but it seems clear that microwave-specific
thermal effects can be observed and potentially exploited.
The goal of this study was to quantify microwave-specific
effects in a homogeneous organic reaction. In this and the
preceding manuscript, we selected reaction systems with the
objective of producing unambiguous results, without regard for
synthetic utility. Importantly, our approach constitutes a more
rigorous method for identifying and quantifying microwave
effects. The method relies on first carrying out a complete
kinetic analysis of the conventional thermal reaction from
which the Arrhenius parameters can be determined. From the
Arrhenius equation, and the kinetic results under microwave
conditions we can determine the magnitude of any deviation
from standard Arrhenius kinetics.
EXPERIMENTAL SECTION
■
Materials. Naphthalene (Aldrich, scintillation grade, ≥99%),
mesitylene (≥99%), n-decane (≥99%), and allyl phenyl ether (99%)
were obtained commercially and used as received. It should be noted
that we specifically specify the producer and grade of naphthalene used
because variations in source and grade were observed to affect the
microwave reaction, presumably due to variations heat capacity.
Allyl p-Nitrophenyl Ether (ApNE). ApNE was synthesized following
the established procedure for the synthesis of allyl phenyl ether. 83.5
g (0.6 mol) of 4-nitrophenol (98%) was mixed with 63 mL (0.72 mol)
of allyl bromide (99%), 100 g (0.72 mol) of potassium carbonate
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(
>99.0%), and 200 mL of reagent grade acetone (>99.5%) in a 1000
mL round-bottomed flask. The solution was refluxed for 6 h and then
allowed to stand overnight at room temperature. Deionized (DI) water
(1000 mL) was added to the product solution, which was then
extracted twice into dichloromethane (100 mL) (>99.5%). The
extracted organic layer was washed three times with 30 mL of 5% w/w
KOH solution (5 g of KOH/100 g water) and finally with deionized
water. The organic layer was then dried for 30 min with 1 g of
magnesium sulfate anhydrous (99.8%). The product was filtered, and
the dichloromethane was evaporated using a rotary evaporator. The
resulting product was a viscous liquid, which solidifies on standing in
the freezer.
The product was subsequently purified by recrystallization. The
crude product was dissolved in 100 mL of reagent grade toluene
99.5%), to which 0.5 g of activated charcoal was added for
decolorization. The solution was filtered with through a medium frit
packed with a layer of anhydrous magnesium sulfate. The filtered
solution was then placed in rotary evaporator to remove approximately
A pertinent question, however, is whether microwave-specific
thermal effects can yield a practical advantage in organic
synthesis. For the constant power reactions, the 0.5 M solution
had a reaction half-life of 5.7 h in the microwave compared to
22.5 h thermally at the same temperature, suggesting that a
useful advantage could be realized. Conversely, the constant
temperature reaction gave a marginal microwave enhancement
with a half-life for the 0.5 M solution of 4.5 h compared to 6.9 h
thermally at 200 °C. Notably, the microwave-specific advantage
diminished at lower concentrations in both methods. The most
intriguing result, however, is the use of microwave-driven
temperature pulses, which showed the largest rate enhance-
ments and suggested a definitive advantage if there is a desire to
keep the bulk solution temperature low. We also note that
parameters that control the magnitude of a pulsed heating effect
are far from understood, and, certainly, optimization of this
process could potentially lead to large enhancements in
reactivity. One approach to exploiting the pulse microwave
effect may be to reduce the thermal contribution to the overall
reaction by speeding up the cooling process through methods
such as strong external cooling of the reaction vessel. Finally,
the specific chemical system (reactant and solvent) will have a
large effect on the magnitude of any microwave effect,
suggesting that understanding and developing parameters for
optimizing heat accumulation are likely to yield useful new
microwave-specific processes. The system studied here was
optimized for maximum microwave absorption by increasing
the dipole moment of the absorbing species and through the
choice of solvent. Among the strongest microwave absorbers
are ionic compounds, which tend to be strongly absorbing at
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0% of toluene. Petroleum ether (50 mL) was then added to
concentrated solution, and it was placed in the freezer and allowed to
precipitate. Once the precipitate was form, the mother liquor was
decanted, leaving behind the product. The purified product was stored
in a freezer to maintain its solid state, and the color of the precipitate
was light yellow. Typical yield after two recrystallizations was about 12
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6
g (11%). Characterization data matched previous reports. Anal.
Calcd for C H NO : C, 60.33; H, 5.06; N, 7.82. Found: C, 60.55; H,
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5
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.07; N, 7.76. H NMR (CDCl , 600 MHz) δ 8.13 (d, J = 9.2 Hz, 2H),
3
.90 (d, J = 7.4 Hz, 2H), 6.00−5.94 (m, 1H), 5.38 (dd, J = 17.3, 1.3
Hz, 1H), 5.27 (dd, J = 10.5, 1.1 Hz, 1H), 4.57 (d, 2H) (Figure S1).
2
-Allyl-4-Nitrophenol (ANP). ANP was synthesized by the Claisen
rearrangement of p-nitro allyl phenyl ether. Neat allyl p-nitro phenyl
(4 g) was heated at 220 °C in an oil bath for 15 min. The product was
separated by column chromatography through high purity grade silica
gel with a pore size of 60 Å and 200−400 mesh particle size. The
column was prepared with a slurry of silica gel in hexane. The crude
product was pipetted on the column and eluted with hexane to
selectively remove the unreacted starting material. The product was
subsequently eluted with dichloromethane. The product was collected
after column chromatography, and the solvent was removed, leaving a
yellow solid that was rinsed with warm hexane. Anal. Calcd for
C H NO : C, 60.33; H, 5.06; N, 7.82. Found: C, 60.40; H, 5.14; N,
2
.45 GHz due to conductivity contributions to the dielectric
37−41
loss in that frequency range.
In fact, recent studies from
our laboratories were specifically designed to exploit the heating
properties of ionic compounds, and significant microwave rate
42,43
enhancements were observed.
Ionic inorganic complexes
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1
are often catalysts for organic transformations, and they are
7.78. H NMR (CDCl , 600 MHz) δ 8.00 (s, 1H), 7.99 (d, 1H), 6.83
3
excellent candidates for realizing significant microwave
(d, 1H), 5.97−5.90 (m, 1H), 5.65 (s, 1H), 5.19 (dd, J = 10.1, 1.3 Hz,
H), 5.16 (dd, J = 17.2, 1.3 Hz, 1H), 3.41 (d, 2H) (Figure S2).
Methods. Solutions of ApNE of a specific concentration were
made by weighing a sample of ApNE and then determining the
volume of naphthalene that was required to reach the desired
concentration. The mass of naphthalene required to give the requisite
volume was calculated from the density of liquid naphthalene, which
was determined experimentally to be 9.733 ± 0.002 g mL .
The concentration of ApNE and ANP present in solution was
determined by means of gas chromatography. Measurements were
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enhancement. In this regard, recent studies by Yamada et
al. reported a very interesting microwave effect in a copper
triflate-catalyzed Claisen rearrangement, in which rate was
increased without a corresponding decrease in enantioselec-
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tion.
On the basis of the experiments, data, and observations
described herein, we conclude that microwave-specific rate
enhancements of homogeneous chemical reactions can occur
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dx.doi.org/10.1021/jo5011526 | J. Org. Chem. XXXX, XXX, XXX−XXX