Determination on temperature gradient of different polar reactants in reaction mixture under microwave irradiation with molecular probe

Article abstract of DOI:10.1016/j.tet.2016.07.041

Temperature accurate measurement is one of key issues in illustration of the rate increase in the microwave-promoted organic reactions because reaction rates are closely related with reaction temperature. The use of molecular probe is reported as a tool to identify the microwave selective heating effects in homogenous reaction mixture of intramolecular aromatic Claisen rearrangement. Our results show direct evidence for localized superheating of polar reactants in nonpolar solvent. While in the polar solvent, the microwave selective heating effects of polar reactants will be decreased.

Full text of DOI:10.1016/j.tet.2016.07.041

Tetrahedron 72 (2016) 5515e5520
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Determination on temperature gradient of different polar reactants
in reaction mixture under microwave irradiation with molecular
probe
*
Xinhao Li, Jiaxi Xu
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology,
Beijing 100029, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 May 2016
Received in revised form 11 July 2016
Accepted 12 July 2016
Available online 14 July 2016
Temperature accurate measurement is one of key issues in illustration of the rate increase in the
microwave-promoted organic reactions because reaction rates are closely related with reaction tem-
perature. The use of molecular probe is reported as a tool to identify the microwave selective heating
effects in homogenous reaction mixture of intramolecular aromatic Claisen rearrangement. Our results
show direct evidence for localized superheating of polar reactants in nonpolar solvent. While in the polar
solvent, the microwave selective heating effects of polar reactants will be decreased.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Microwave
Hot spot
Claisen rearrangement
Molecular probe
Temperature gradient
1. Introduction
equation for certain types of reactions.4a,d However, some of the
further studies on the hypothesized nonthermal effects were
Since the first published report in 1986,1 microwave-assisted
organic synthesis has been widely developed. Virtually all types
of thermally driven chemical reactions have been studied under
microwave irradiation.2 Under microwave irradiation conditions,
some organic reactions can be accelerated obviously. In some cases,
this powerful technique can produce higher yields, different se-
lectivity, and lower side products.3 Such useful performances of
microwave irradiation (MWI) have sparked considerable specula-
tions and discussions into the essence of the microwave heating.
Much of the debate has focused on the question whether the ac-
celeration can be rationalized by purely thermal effects or some
specific microwave effects.4
proven incorrect later. Subsequent careful reinvestigations revealed
that the reaction results were quite close to those of the conven-
tional reactions run at the same temperature. The so-called ‘mi-
crowave effects’ were mainly due to the flawed temperature
measurement of the reaction mixture or subtle differences of re-
action conditions.4e,5
The vast majority of microwave accelerated reactions can be
explained as the thermal effects arising from the extremely fast
heating rate, which cannot be reproduced by classical heating. By
using an external heat source, heat first passes through the walls
of the vessel and then reaches the reaction mixture. It results in
the temperature of reaction mixture being lower than that of the
vessel until sufficient time to achieve thermal equilibrium. Mi-
crowave irradiation, on the other hand, directly couples with the
molecules inside the reaction mixture, leading to a rapid rise in
temperature.6 Microwave irradiation does not change the acti-
vation energy, but provides the momentum to overcome the
energy barrier of reactions more quickly. In addition, the ‘inver-
ted heat transfer’ effect7 (from the reaction mixture towards the
exterior) can arouse the overheating of liquids above the normal
boiling point,8 since boiling nuclei are formed at the surface of
the liquid. This overheating effect could explain the acceleration
of reactions.
Nonthermal microwave effects4a,c were speculated previously as
results from the directly coupling interaction between microwave
electric field and polar molecules (reactants, intermediates, and
even transition states) in the reaction mixtures, which did not
generate a macroscopic change in reaction temperature. It was
argued that microwave electric field affected the orientation of
polar molecules or intermediates and hence changed the pre-
exponential factors A or the activation energies in the Arrhenius
* Corresponding author. Fax: þ86 10 6443 5565; e-mail address: jxxu@mail.buct.edu
(J. Xu).
http://dx.doi.org/10.1016/j.tet.2016.07.041
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

5516
X. Li, J. Xu / Tetrahedron 72 (2016) 5515e5520
While some specific reaction results under microwave irradia-
a useful probe for investigation of nonthermal microwave ef-
fects.14,15 The results indicate that no obvious effect of microwave
irradiation on the diastereoselectivity was observed in the Stau-
dinger reactions. The increase of polarity of intermediates did not
accelerate the reaction or alter the diastereoselectivity.
tion could not be rationalized simply by rapid heating or flawed
temperature measurement. For example, Yamada and co-workers
reported a copper triflate-catalyzed asymmetric Claisen rear-
rangement,9 in which the reaction was accelerated under the mi-
crowave irradiation without
a
corresponding decrease in
In this study, our group uses reactant molecules as a tempera-
ture probe in an effort to identify the microwave selective heating
effects in homogenous reaction mixture. In this way, temperature
gradient can be directly observed.
enantioselectivity. The linear relationship between ln[ee] and 1/T
was revealed that the enantioselectivity decreased as the internal
reaction temperature increased.
MW energy directly heats specific molecules in the reaction
mixture through the loss processes. For a specific molecule, the
ability to convert microwave energy into heat is determined by the
2. Results and discussion
loss tangent (tan d
).6 Compounds with high loss tangent tend to
For a specific material or solvent, the ability to convert micro-
wave energy into heat at a given frequency and temperature is
determined by the so-called loss tangent (tan d). The value of loss
tangent is expressed as tan
absorb the MW energy whereas less polar substances are poor
absorbers. In this way, absorption of the radiation and heating may
perform selectively.
d
¼ε00/ε0, where ε00 is the dielectric loss,
Huang and Richert proposed a microwave selective heating
model that the flow of microwave irradiation can potentially trigger
the selective heating of a dipolar molecule in a non-absorbing
solvent.10 The microwave absorbing molecules (‘domains’) assimi-
late microwave energy and accumulate the heat, resulting in an
instantaneous localized superheating (‘hot spots’). The amount of
accumulated heat can potentially give rise to microwave specific
rate enhancement.
indicative of the efficiency with which the electromagnetic radia-
tion is converted to heat, and ε0 is the dielectric constant describing
the polarizability of molecules in the electric field. In general, ma-
terials with large permanent dipole moment could strongly absorb
microwave energy and, consequently, for efficient heating.5,7 In this
study, we prospect to use a two-substrate-based aromatic Claisen
rearrangement of allyl 4-nitrophenyl ether (ANE) and allyl 4-
methylphenyl ether (AME) as a tool for probing the selective
heating effect of microwave irradiation on molecular level (Scheme
1). Aromatic Claisen rearrangements are suitable as model re-
actions because they are typical intramolecular reaction followed
simple first-order kinetics. The effective temperature is easy to be
obtained from the measured rate constants and Arrhenius Equa-
tion. With a significantly large dipole moment, ANE could effec-
tively convert MW energy into heat, and the accumulated heat will,
in our hypothesis, potentially create a high thermal energy ‘do-
main’, whereas the weak-polar AME could slightly absorb the MW
energy and only be heated by the surroundings through the con-
vective heating in polar solvent. Therefore, AME is considered likely
to be suitable as a temperature probe for the bulk solution. This
protocol does not require calibrated temperature monitoring de-
vices and the strict control of microwave reactor. It can simulate the
reaction conditions applied widely in microwave-assisted organic
reactions.
Schmink and Leadbeater used in situ Raman spectroscopy as
a tool for probing the selective heating effects of microwave irra-
diation.11 Raman monitoring can detect reaction mixture on a mi-
croscopic level. While the microwave energy may interact with the
polar molecules more so than with nonpolar ones, the results in-
dicate that more polar molecules are not at a higher temperature.
They conclude that the reason is that the conversion of electro-
magnetic energy into kinetic energy is slower than conversion of
kinetic energy into thermal energy. That is, the selective heating of
microwave irradiation could not cause the microscopic ‘hot spots’.
The experimental evidence of MW selective heating that is in
accord with the model of Huang and Richert was reported by
Dudley’s group.12 They observed detectable heat accumulation and
microwave specific rate enhancement for the aromatic Claisen
rearrangement of allyl 4-nitrophenyl ether in benzene (a nonpolar
solvent). The effective temperatures calculated from the measured
reaction rate based on Arrhenius plots were higher than the tem-
perature measured by the calibrated internal fiber probe, demon-
strating the excess heat is accumulated in the ‘domain’ and
resulting in a reaction accelerating. This unique MW selective
heating mechanism cannot be duplicated by convective heating
process.
Generally, in order to evaluate or to attest the existence of MW
effects, the temperature of the reaction mixture must be accurately
measured. Unfortunately, currently common temperature moni-
toring devices, such as external infrared monitors and internal fiber
monitors, are not the best choices to measure the internal tem-
perature of reactions veritably and accurately.4e,13 External infrared
temperature monitors record the temperature on the outer surface
of the reaction vessel and do not precisely reflect the temperature
of the reaction mixture. Internal fiber-optic monitors are more
accurate but only measure the temperature at several single
positions of the reaction mixture. Importantly, in selective heating
mechanism, the ‘domains’ can directly couple with microwave
energy and thus create microscopic hot spots at the molecular level.
The temperature gradient between ‘domains’ and surroundings, if
exists, cannot be measured by commercially available temperature
monitoring devices.
Scheme 1. Two-substrate-based aromatic Claisen rearrangement of allyl 4-nitrophenyl
ether (ANE) and allyl 4-methylphenyl ether (AME).
Solvents play a very important role in microwave-assisted or-
ganic reactions. The more polar a solvent is, the greater its ability to
couple with the microwave energy and the faster the temperature
of the reaction mixture increases. Clearly, the solvent effect is of
great importance with regard to the possibility of the microwave
selective heating. We conducted the same Claisen rearrangements
under microwave irradiation both in a polar solvent (N-methyl-
pyrrolidone, NMP, a favorable microwave absorbance solvent with
Molecular probes have advantage in the measurement of in-
ternal temperature of reaction mixture on molecular level com-
pared with the physical temperature monitoring devices. Our
group used diastereoselectivity in the Staudinger reaction as
loss factor tan d 0.275) and in a nonpolar one (n-tetradecane). All of

X. Li, J. Xu / Tetrahedron 72 (2016) 5515e5520
5517
the reaction mixtures described in this report were macroscopically
homogeneous and effectively stirred. The heating curves at 50 W of
microwave power are shown in Fig. 1. The heating rate and the
steady-state temperature of 0.1 M of ANE and AME in n-tetradecane
are markedly different. n-Tetradecane shows little microwave
heating in its pure form, but when 0.1 M of ANE is dissolved in it,
the stronger heating is observed (the steady-state temperature is
158 ꢀC). The weak polar AME is heated poorly under microwave
irradiation and the heat rate and steady-state temperature of
a 0.1 M solution of AME dispersed in n-tetradecane are almost the
same as the pure n-tetradecane. These heating performances are
extremely suitable for our investigation that the strong microwave
absorbing ANE plays the role of ‘Molecular radiator’ and reacts at
a higher effective temperature. While in the polar solvent NMP, the
heating curves are almost the same. As a result, the selective
heating would be shaded to a certain extent and the effective
temperature of ANE and AME will, as our prospects, be the same.
naphthalene as an internal standard. The measured rate constants
are summarized in Tables 1 and 2 (For details, see Supplementary
data, sections 3 and 4). The parameters of the Arrhenius equation
are obtained from the measured rate constants (Figs. 2 and 3).
With the Arrhenius parameters in hand, we subsequently tested
the MWI reactions under constant temperature conditions because
the use of constant temperature mode is common in microwave-
assisted organic reactions, particularly when adapting procedures
developed under conventional heating conditions. In this study, all
reactions were conducted under open vessel and constant tem-
perature conditions. All microwave-assisted reactions were con-
ducted in
a commercially available microwave reactor, CEM
Discover systemÔ, equipped with an infrared temperature
detector.
Table 1
Thermal kinetics of the Claisen rearrangements in n-tetradecane
Entry
Temp (ꢀC)
k (ꢂ10ꢃ3) (minꢃ1
)
For ANE
For AME
1
2
3
4
5
6
180
195
200
205
210
215
0.21ꢁ0.01
0.61ꢁ0.03
0.77ꢁ0.01
1.02ꢁ0.03
1.39ꢁ0.04
2.05ꢁ0.06
0.80ꢁ0.01
1.78ꢁ0.04
2.25ꢁ0.04
3.02ꢁ0.10
3.68ꢁ0.02
4.54ꢁ0.07
Table 2
Thermal kinetics of the Claisen rearrangements in NMP
Entry
Temp (ꢀC)
k (ꢂ10ꢃ3) (minꢃ1
)
For ANE
For AME
1
2
3
4
5
170
180
190
200
210
0.64ꢁ0.02
1.02ꢁ0.03
1.49ꢁ0.07
2.13ꢁ0.09
2.85ꢁ0.07
0.33ꢁ0.01
0.54ꢁ0.02
1.08ꢁ0.04
2.07ꢁ0.05
3.88ꢁ0.10
Fig. 1. (a) Microwave heating curves of 0.1 M allyl 4-methylphenyl ether and allyl 4-
nitrophenyl ether in n-tetradecane at 50 W of applied microwave power; (b) Micro-
wave heating curves of 0.1 M allyl 4-methylphenyl ether and allyl 4-nitrophenyl ether
in NMP at 50 W of applied microwave power.
Fig. 2. Arrhenius plots of the rate and temperature data of rearrangements of ANE and
AME in n-tetradecane at 180, 195, 200, 205, 210, and 215 ꢀC. The activation energy
Ea¼115.2 kJ molꢃ1 and the pre-exponential factor A¼4.1ꢂ109 sꢃ1 for the rearrange-
ment of ANE and the activation energy Ea¼89.9 kJ molꢃ1 and the pre-exponential
factor A¼1.9ꢂ107 sꢃ1 for the rearrangement of AME. See the Supplementary data for
tabular data.
Before embarking on an investigation of microwave assisted
reactions, the kinetic behaviors of the reactions were studied in
a preheated temperature-controlled oil bath. The reaction tem-
perature was carefully controlled within less than ꢁ1 ꢀC with a fine
temperature controller in a big oil bath with a large amount of
silicone oil, and a thick asbestos coating outside the bath. The
disappearance of ANE and AME was measured as a function of time
at six different temperatures between 180 ꢀC and 215 ꢀC in n-tet-
radecane and five different temperatures between 170 ꢀC and
210 ꢀC in NMP. The plots of the natural logarithms of the concen-
trations of ANE and AME versus time at each temperature followed
the expected first-order kinetics. The concentrations of ANE and
ANP present in solution were determined by means of HPLC with
2.1. MWI reactions in n-tetradecane
As can be seen in Table 3, three parallel experiments data show
that there is a significantly temperature gradient between the ef-
fective temperatures of ANE and AME. Obviously, the observed
temperature gradient is in accord with the model of Huang and
Richert as the result of the selective heating. In the microwave
transparent solvent, the MW energy couple with the polar solute
(ANE), creating high thermal energy ‘domains’. The temperature
inside the domains is higher than the temperature of the bulk

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X. Li, J. Xu / Tetrahedron 72 (2016) 5515e5520
The above results reveal that microwave assisted reactions occur
at higher temperature than the setup temperature, generally higher
more than 10 ꢀC, herein, even more than 35 ꢀC for the Claisen
rearrangement, an intramolecular first-order reaction. It can be
seen from Tables 1 and 2 that the reaction constants increase two to
three times if the reaction temperature increases 20ꢀ. On the other
hand, microwave heating is more faster than the convention
heating. Thus, overheating and fast heating are two of major rea-
sons that accelerate the reactions under microwave irradiation
conditions.
2.3. Influence of reactant concentration and microwave
power on the temperature gradient
Fig. 3. Arrhenius plots of the rate and temperature data of rearrangements of ANE and
AME in NMP at 170, 180, 190, 200, and 210 ꢀC. The activation energy Ea¼70.1 kJ molꢃ1
and the pre-exponential factor A¼1.2ꢂ105 sꢃ1 for the rearrangement of ANE and the
activation energy Ea¼110.3 kJ molꢃ1 and the pre-exponential factor A¼3.1ꢂ109 sꢃ1 for
the rearrangement of AME. See the Supplementary data for tabular data.
According to the mechanism of microwave dielectric heating,
only the polar molecules selectively absorb microwave energy,
nonpolar molecules cannot transform electromagnetic energy into
heat. Therefore, it is considered that in nonpolar solvent n-tetra-
decane, the temperature gradient would increase when the con-
centration of ANE increases. So we performed the reactions at
different concentrations in n-tetradecane with a newly calibrated
microwave equipment. Although after new calibration the derived
temperatures are different from previous ones even under the same
reaction sets (data in Table 3 vs data in entry 1 in Table 5 and data in
entry 4 in Table 6), our method need not determine exact absolute
temperature, it determines temperature gradient. Thus, the results
obtained in the newly calibrated microwave equipment do not
impact our conclusion. The results are shown in Table 5. As we can
see, the temperature gradients increase as the concentrations of the
polar reactant ANE increase. The effective temperature of AME does
not change when the concentration changes and is equal to the
setup temperature. The observed tendency indicates that when the
concentration of the ANE increases, there are more ‘hot-spot’ in the
reaction mixture, resulting in higher effective temperature of ANE.
Thus, greater temperature gradient was observed between ANE and
AME.
Table 3
MWI Reactions in n-tetradecanea
Trial
k (ꢂ10ꢃ3) (minꢃ1
)
Effective T (ꢀC)
T Gradient (ꢀC)b
ANE
AME
ANE
AME
1
2
3
1.47ꢁ0.06
1.74ꢁ0.05
1.61ꢁ0.05
1.67ꢁ0.04
1.64ꢁ0.06
1.59ꢁ0.09
210
213
212
194
194
193
17
19
19
a
Microwave setup: 180 ꢀC, 300 W, Powermax off, stir high, constant temperature
mode. Concentrations [ANE]¼[AME]¼0.1000 mol/L.
b
T gradient is the temperature difference between ANE and AME.
solution. Notably, bulk solvent superheating (15 ꢀC) was observed.
This is possibly because of the flawed temperature measurement of
the external infrared monitor, which was not calibrated, or the high
output microwave power (300 W). No matter what the reason, this
does not affect the conclusion because the reaction mixture is ho-
mogenous. This unique MW selective heating mechanism cannot
be duplicated by convective heating process.
Table 5
MWI Reactions in n-tetradecane at different concentrationsa
2.2. MWI reactions in NMP
[M]b mol/L
k (ꢂ10ꢃ3) (minꢃ1
)
Effective T (ꢀC)
T Gradient (ꢀC)c
For the sake of strict comparison, the setups of MWI reactions in
the solvent of NMP are the similar as those in the solvent of n-
tetradecane. The results of MWI reactions in NMP are shown in
Table 4. As expected, the temperature gradient is decreased as the
polarity of solvent increasing. Microwave absorbing solvent NMP
increases the overall microwave absorbing ability of the bulk and
simultaneously heats the molecules of AME and ANE, resulting in
the decrease of the temperature gradient. Notably, a more signifi-
cant superheating phenomenon was observed as well. In the con-
stant temperature mode, the microwave initially applied high
power to get the solution to the desired temperature at an appro-
priate rate. And then, the power decreases and maintains at a lower
level to keep the temperature constant. The initial high output
power may have a greater influence to the reaction mixture in NMP
because of the strong microwave absorbing ability, resulting in
a higher bulk temperature.
ANE
AME
ANE
AME
0.1000
0.2000
0.3000
0.82ꢁ0.04
1.12ꢁ0.06
1.27ꢁ0.01
1.31ꢁ0.03
1.48ꢁ0.08
1.46ꢁ0.07
201
206
208
189
191
191
12
15
17
a
Microwave setup: 190 ꢀC, 300 W, Powermax off, stir high, constant temperature
mode. The data were obtained on a newly calibrated equipment.
b
Concentration [M]¼[ANE]¼[AME].
c
T gradient is the temperature difference between ANE and AME.
Table 6
MWI Reactions in n-tetradecane at different microwave powers.a
Power (W)
k (ꢂ10ꢃ3) (minꢃ1
)
Effective T (ꢀC)
T Gradient (ꢀC)d
ANE
AME
ANE
AME
300b
200b
100c
300c
0.67ꢁ0.01
0.44ꢁ0.02
0.86ꢁ0.02
1.27ꢁ0.01
1.11ꢁ0.02
0.87ꢁ0.05
1.35ꢁ0.03
1.46ꢁ0.07
197
191
201
208
185
181
189
191
12
10
12
17
Table 4
MWI reactions in NMPa
a
Microwave setup: Powermax off, stir high, constant temperature mode. The
data were obtained on a newly calibrated equipment.
Trial
k (ꢂ10ꢃ3) (minꢃ1
)
Effective T (ꢀC)
T Gradient (ꢀC)b
b
Concentration [ANE]¼[AME]¼0.1000 mol/L. Setup temperature 180 ꢀC.
c
Concentration [ANE]¼[AME]¼0.3000 mol/L. Setup temperature 190 ꢀC.
ANE
AME
ANE
AME
d
T gradient is the temperature difference between ANE and AME.
1
2
3
3.60ꢁ0.08
4.09ꢁ0.20
3.87ꢁ0.04
4.13ꢁ0.04
4.96ꢁ0.05
4.53ꢁ0.05
214
218
216
212
215
214
2
3
2
It should also be noted that the level of the microwave heating
depends on the amount of microwave energy transmitted to the
reaction mixture. So we next investigated the effect of microwave
power on the reaction kinetics. MWI reactions at different
a
Microwave setup: 180 ꢀC, 300 W, Powermax off, stir high, constant temperature
mode. Concentrations [ANE]¼[AME]¼0.1000 mol/L.
b
T gradient is the temperature difference between ANE and AME.

X. Li, J. Xu / Tetrahedron 72 (2016) 5515e5520
5519
microwave powers in n-tetradecane with a calibrated microwave
4.2. General procedure for preparation of allyl 4-substituted
phenyl ethers
equipment were performed. The results are summarized in Table 6.
At power 300 W, the temperature gradient is 12 ꢀC (Table 6, entry
1). The effective temperature of AME is 5 ꢀC higher than the setup
temperature, it may be the result of the high microwave power.
Decreasing the power to 200 W, the temperature gradient slightly
decreases to 10 ꢀC and the effective temperature of AME is equal to
the setup temperature (Table 6, entry 2). When the reaction was
performed in 100 W, the reaction mixture cannot be heated to
180 ꢀC. So, we increased the concentrations of ANE and AME to
0.3000 mol/L and performed the reactions at 100 W and 300 W
with the setup temperature 190 ꢀC (Table 6, entries 3 and 4). The
results show that the temperature gradient increases when the
microwave power increases.
Allyl aryl ethers were synthesized following the established
procedure.16 4-Substituted phenol (0.3 mol), allyl bromide (32 mL,
0.36 mol), potassium carbonate (50 g, 0.36 mol), and 100 mL of dry
acetone were added in a 500 mL round-bottomed flask. The solu-
tion was refluxed for 6 h. After cooled, 500 mL of deionized water
was added to the solution, which was then extracted twice with
dichloromethane (50 mL). 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 over anhydrous sodium sulfate. After dichloromethane was
evaporated using a rotary evaporator, the residue was distilled
under reduced pressure or crystallized.
3. Conclusion
4.2.1. Allyl 4-nitrophenyl ether (ANE). After concentration at re-
duced pressure, the residue was recrystallized in a mixture of tol-
uene and petroleum ether in an ice-water bath to afford light
The current results indicate that microwave selective heating
can be achieved in homogeneous organic reaction mixture, and
that, the selective heating can result in a measurable temperature
gradient among different polar reactants in reaction mixture under
certain conditions, such as in nonpolar solvents. The concentration
of the polar reactants and the microwave power affect the tem-
perature gradient.
yellow crystals, mp 27e28 ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.20 (d,
J¼9.3 Hz, 2H), 6.97 (d, J¼9.3 Hz, 2H), 6.05 (ddd, J¼22.5, 10.5, 5.3 Hz,
1H), 5.44 (dd, J¼17.3, 1.3 Hz, 1H), 5.35 (dd, J¼10.5, 1.2 Hz, 1H), 4.64
(d, J¼5.3 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d 163.6, 141.6, 131.9,
125.9, 118.6, 114.7, 69.4.
For homogeneous solution phase organic reactions, both the
polarity of reactants and solvent play significant roles in
microwave-assisted reactions. A polar solvent is necessary if the
reactants are non-absorbing (nonpolar) for fast heating. The polar
solvents couple very efficiently with the microwave energy, leading
to a rapid rise in internal temperature of the reaction mixture
synchronously. When the reactants are strong-absorbing, though
nonpolar solvents do not couple well with microwave energy, re-
actions can be also accelerated by the microwave irradiation: ex-
cess heat will be produced from the direct interaction between
polar reactants and microwave irradiation, and hence, accelerates
the reaction while the average internal temperature remains low.
But the occurrence of microwave selective heating polar re-
actants in nonpolar solvent is little practical applications. The re-
action mixture of nonpolar solvent needs a high microwave power
and is heated really slow compared to that of polar solvent, the vast
majority of microwave energy are wasted. In addition, the Claisen
rearrangements we used in this study are typical intramolecular
reactions, they can undergo the rearrangement within the domains
without transmit heat to other reactants. Thus, obviously different
temperature gradient is observed between different polar re-
actants. Our results also indicate that overheating and fast heating
are two of major reasons that accelerate the reactions under mi-
crowave irradiation conditions.
4.2.2. Allyl 4-methylphenyl ether (AME). After concentration at re-
duced pressure, the residue was purified by reduced pressure dis-
tillation to afford clarity liquid at 68e69 ꢀC/0.04 MPa; 1H NMR
(400 MHz, CDCl3)
d
7.07 (d, J¼8.5 Hz, 2H), 6.81 (d, J¼8.4 Hz, 2H),
6.05 (ddd, J¼16.5, 10.5, 5.3 Hz, 1H), 5.39 (dd, J¼17.3, 1.4 Hz, 1H), 5.26
(dd, J¼10.5, 1.2 Hz, 1H), 4.50 (d, J¼5.3 Hz, 2H), 2.28 (s, 3H). 13C NMR
(101 MHz, CDCl3) d 156.4, 133.5, 129.9, 129.8, 117.3, 114.5, 68.8, 20.4.
4.3. General procedure for preparation of 4-substituted 2-
allylphenols
4-Substituted 2-allylphenols were synthesized by the Claisen
rearrangement of allyl 4-substituted phenyl ethers. A solution of an
allyl aryl ether (4-nitrophenyl ether (537 mg, 3 mmol) in 4 mL of
tetradecane or 1 mL of pure allyl 4-methylphenyl ether) was stirred
at 220 ꢀC for 4 h under microwave irradiation in a sealed vessel. The
reaction mixture was cooled and extracted with saturated sodium
hydroxide solution. The combined basic solution was washed twice
with dichloromethane, and then acidified to pH¼1 with concen-
trated hydrochloric acid. The resulting mixture was extracted three
times with dichloromethane. The combined organic phase was dried
over anhydrous sodium sulfate. After concentration at reduced
pressure, the residue was purified by silica gel column chromatog-
raphy with ethyl acetate and petroleum ether (1:5, v/v) as eluent.
4. Experimental section
4.1. General information
4.3.1. 2-Allyl-4-nitrophenol. White solid, mp 82e83 ꢀC, lit.16 mp
79.0e79.6 ꢀC. 1H NMR (400 MHz, CDCl3)
d 8.11e8.05 (m, 2H), 6.92
(d, J¼8.6 Hz, 1H), 6.37 (s, 1H), 6.01 (ddt, J¼16.7, 10.2, 6.5 Hz, 1H),
Melting points were determined on a Yanaco MP-500 melting
point apparatus and are uncorrected. All 1H (400 MHz) and 13C
NMR (101 MHz) spectra were recorded on a Bruker 400 NMR
spectrometer in CDCl3 with TMS as an internal standard and
chemical shifts are reported in ppm. All coupling constants (J) in 1H
NMR are absolute values given in hertz (Hz) with peaks labeled as
single (s), broad singlet (br), doublet (d), triplet (t), quartet (q), and
multiplet (m). Column chromatography with silica gel
(200e300 mesh) was carried out with petroleum ether (PE,
60 ꢀCe90 ꢀC) and ethyl acetate (EA) as the eluent. n-Tetradecane (J
& K), N-methylpyrrolidone, 4-methylphenol, 4-nitrophenol, and
allyl bromide (J & K) were obtained commercially and used as
received.
5.27e5.15 (m, 2H), 3.47 (d, J¼6.5 Hz, 2H). 13C NMR (101 MHz, CDCl3)
d
160.0, 141.3, 134.6, 126.8, 126.3, 124.2, 117.8, 115.7, 34.4.
4.3.2. 2-Allyl-4-ethylphenol. Colorless liquid; 1H NMR (400 MHz,
CDCl3)
6.92 (d, J¼6.9 Hz, 2H), 6.70 (d, J¼8.7 Hz, 1H), 6.01 (ddt,
d
J¼16.8, 10.4, 6.3 Hz, 1H), 5.23e5.05 (m, 2H), 4.83 (s, 1H), 3.37 (d,
J¼6.3 Hz, 2H), 2.25 (s, 3H). 13C NMR (101 MHz, CDCl3)
d 151.8, 136.5,
130.9, 130.1, 128.2, 125.0, 116.3, 115.6, 35.1, 20.4.
4.4. Kinetic studies
10 mL of reaction mixture (0.1 M of AME and ANE, 100 mg
naphthalene) reacted under microwave or thermal conditions. At

5520
X. Li, J. Xu / Tetrahedron 72 (2016) 5515e5520
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a periodic time, 0.1 mL of sample was taken out by a syringe with
long needle. The samples were added into 1 mL of acetonitrile and
then diluted to 20 times before analyzing by HPLC. The concentra-
tions of ANE and AME present in reaction mixture were determined
by means of HPLC. Measurements were made on Agilent 1100 HPLC
equipped with a C18 chromatographic column (250ꢂ4.6 mm) with
an eluent of acetonitrile:H2O (60:40, v/v) at a flow rate of 1 mL/min.
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UV detection wavelength was 254 nm. Injection volume was 10 mL.
To calibrate the HPLC response to the concentrations of allyl 4-
nitrophenyl ether and allyl 4-methylphenyl ether, a curve was
constructed by analyzing a series of standard concentrations of each
compound dissolved in acetonitrile by HPLC with naphthalene as
internal standard (Figs. S9 and S10).
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Acknowledgements
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This work was supported in part by the National Basic Research
Program of China (No. 2013CB328905), and the National Natural
Science Foundation of China (Nos. 21372025 and 21172017).
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Supplementary data
13. Kappe, C. O. Chem. Soc. Rev. 2013, 42, 4977e4990.
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Supplementary data related to this article can be found, in the
online version at http://dx.doi.org/10.1016/j.tet.2016.07.041. These
data include MOL files and InChiKeys of the most important com-
pounds described in this article.
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