Infrared irradiation assisted both the synthesis of (Z)-(aminomethyl)(aryl)phenylhydrazones via the Mannich coupling reaction and their application to the palladium-catalyzed Heck reaction

Article abstract of DOI:10.1039/c5ra12715g

The Mannich coupling reaction between arylhydrazones, formaldehyde and a secondary amine to generate the (Z)-(aminomethyl)(aryl)phenylhydrazones 1a-h assisted by infrared irradiation (IR) under solvent-free conditions is herein reported, and the catalytic potential of compounds 1a-h in the palladium-catalyzed and IR-assisted Heck coupling reaction is also evaluated. Coupling products are obtained in high yields and short reaction times. We show the advantages of this new alternative to promote both Mannich and Heck coupling reactions.

Full text of DOI:10.1039/c5ra12715g

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: F. Ortega
Jiménez, J. G. Penieres Carrillo, S. Lagunas-Rivera, J. G. López-Cortés, C. Alvarez Toledano and M. C.
Ortega-Alfaro, RSC Adv., 2015, DOI: 10.1039/C5RA12715G.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Please do not adjust margins
RSC Advances
Page 1 of 7
View Article Online
DOI: 10.1039/C5RA12715G
Journal Name
ARTICLE
Infrared irradiation assisted both the synthesis of (Z)-
aminomethyl)(aryl)phenylhydrazones via the Mannich coupling
(
0
Received 00th January 20xx,
reaction and its application to the palladium-catalyzed Heck
reaction.
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
a
a
a
Fernando Ortega-Jiménez *, José Guillermo Penieres-Carrillo , Selene Lagunas-Rivera ,
b
b
c
José G. López-Cortés , Cecilio Alvarez-Toledano and M. Carmen Ortega-Alfaro .
The Mannich coupling reaction between arylhidrazones, formaldehyde and a secondary amine to generate the (Z)-
(aminomethyl)(aryl)phenylhydrazones 1a-h assisted with infrared irradiation (IR) under solvent-free conditions is herein
reported, and the catalytic potential of compounds 1a-h in the palladium-catalyzed and IR-assisted Heck coupling reaction
are also evaluated. Coupling products are obtained in high yields and short reaction times. We show the advantages of this
new alternative to promote both Mannich and Heck coupling reactions.
1
0
inert conditions. Nevertheless, the high cost of phosphines and
their sensitivity to air and moisture conditions have favored the
development more robust new catalytic systems based on different
ligands and/or phosphine-free catalytic systems. Among ligands
with different donor groups, we can find extensive examples that
Introduction
Since its early application, the Mannich reaction has become a
powerful tool for the synthesis of various β-amino ketones and
esters, which are versatile synthetic building blocks for the
preparation of compounds containing nitrogen, and privileged
16
17
include N-heterocyclic,
carbocyclic, and anionic carbocyclic
18
19
20
21
22
carbenes, Schiff bases, pyridines, imidazoles, pyrazoles,
1
structures useful in synthetic and medicinal chemistry. In this
23
24
25
26
27
oxazolines, hydrazones, selenides, ureas, thioureas, among
others. Extensive studies have shown the efficiency and robustness
context, the Mannich reaction of hydrazones has only shown
2
moderate to good yields using formaldehyde. This methodology
28
29
of
palladacycles,
pincer-type
Pd(II) species supported in mesoporous
materials, etc. in performing this coupling reaction
complexes,
palladium
was extended allows efficient coupling reactions between
30,31
nanoparticles,
2
b
hydrazones, another aldehydes and secondary amines. The
hydrazones and their derivatives are a versatile class of compound
32
3
4
mainly useful in heterocycle synthesis, as organocatalysts, and as On the other hand, new experimental methodologies based on non-
5
ligands in metallic complexes. Aryl hydrazones are applied as convectional energy sources for the activation of chemical reactions
6
33
efficient ligands in the palladium-catalyzed Heck reaction, the different to conventional heating, such as microwaves,
coupling reaction of Suzuki, the reaction of Hiyama, and the ultrasound, mechanochemistry and infrared,
7
8
34
35
36-39
have gained
9
coupling reaction of allyl acetate with boric acid.
growing attention in recent years, as an important section of what
4
0
is nowadays known as Green Chemistry. In particular, microwave
irradiation under controlled conditions is an invaluable technology
that has enormous applications in different areas, including
The Heck reaction is one of the most general and useful method for
1
0
the formation of C-C bonds. This coupling reaction has a wide
variety of applications including total synthesis of natural
41a
41b
academic and industrial researches. However, the successful
use of this methodology is limited to the access of specific and
1
1
12
13
products, fine chemicals syntheses, bioorganic chemistry,
1
4
15
material science and industrial applications, among others.
42
expensive equipment. Infrared irradiation is an energy source
3
6-39
This reaction involves an appropriated chemical source of hardly explored in comparison to other energy sources.
palladium, in combination with phosphine ligands, and a base under
Due to the high value of IR as an energy source for the activation of
chemical reactions, and few precedent in the literature regarding to
the use of infrared irradiation in both Mannich and Heck coupling
reactions, recently we report to use of the IR in the Heck coupling
4
3
reaction with very good results. To continue with the use of IR as
energy source for the activation of chemical reactions, we herein
report a practical and efficient method for the system synthesis of
type (Z)-(aminomethyl)(aryl)phenylhydrazones via Mannich
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 2 of 7
View Article Online
DOI: 10.1039/C5RA12715G
ARTICLE
Journal Name
3
coupling and their application to the palladium-catalyzed Heck turn over numbers (TON) around ~10 . Other sources of palladium
coupling reaction assisted by IR.
were evaluated including PdCl
2
2 2 3 2 2
, Pd(PhCN) Cl and Pd(PPh ) Cl
(
Table 2, entries 7, 8, 9) but these salts obtained moderated yields
Results and discussion
2
in comparison with Pd(OAc) (Table 2, entry 2).
The (Z)-(aminomethyl)(aryl)phenylhydrazones 1a-h were prepared
2
c,d
Table 2. Optimization of the conditions of the Heck coupling
according to a procedure described in the literature
Mannich reaction between formaldehyde (2), a phenylhidrazone
a-d, piperidine or diethylamine as base, under solventless
via the
reaction between p-iodotoluene (4b) and methyl acrylate (5), using
a
hydrazones 1a-h.
3
conditions (chromatography was required for purification) and
using infrared irradiation (IR) as the energy source. This method is
clean and rapid and affords the corresponding (Z)-
(aminomethyl)(aryl)phenylhydrazones 1a-h with very good yields.
Hidrazone
Source of
palladium
Time
(min)
30
Yield
(%)
Table 1. Synthesis of (Z)-(aminomethyl)(aryl)phenylhydrazones 1a-h
Entry
b
Base
c
TON TOF
(
% mol)
using IR as the energy source.
1
2
3
4
5
6
7
8
9
1a (0.05)
1a (0.01)
1a (0.01)
1a (0.01)
1a (0.01)
1a (0.01)
1a (0.01)
Pd(OAc)
Pd(OAc)2
Pd(OAc)
Pd(OAc)2
Pd(OAc)
2
K
3
PO
K3PO4 98 9800 19600
PO 50 5000 1111
150 Na PO 60 6000 2400
4
96 1920 3840
30
2
270 Li
3
4
3
4
2
90
60
30
30
30
K
2
CO
3
30 3000 2000
AcOK 95 9500 9500
K3PO4 86 8600 17200
84 8400 16800
85 8500 17000
K3PO4 85 8500 17000
PO 70 7000 2800
Entry
1
R
1
R
2
Product
1a
Time (min)
Yield [%]
Pd(OAc)2
PdCl2
a
b
a
b
-(CH
-(CH
-(CH
2
2
2
)
)
)
5
5
5
-
-
-
H
120 (180)
92 (90)
a
b
a
b
1a (0.01) Pd(PhCN)
1a (0.01) Pd(PPh
Pd(OAc)2
Pd(OAc)
2
Cl
Cl
2
K
K
3
3
PO
PO
4
2
3
4
5
6
7
8
OCH
Cl
3
1b
1c
1d
1e
1f
120 (180)
80 (80)
3
)
2
2
4
a
b
a
b
45 (120)
90 (87)
10 1b (0.01)
11 1c (0.01)
1d (0.01)
13 1e (0.01)
30
150
a
b
a
b
b
b
b
2
K
3
4
-(CH ) -
NO2
H
15 (45)
99 (97)
2
5
12
Pd(OAc)2
Pd(OAc)2
150 K3PO4 76 7600 3040
a
b
b
a
C
C
C
C
2
2
2
H
5
120 (180)
70 (65)
30
30
30
K3PO4 82 8200 16400
a
a
14
1f (0.01)
1g (0.01)
16 1h (0.01)
Pd(OAc)
Pd(OAc)
2
2
K
K
3
3
PO
PO
4
75 7500 15000
85 8500 1700
H
H
H
5
OCH
Cl
3
120 (180)
85 (80)
15
4
a
b
a
5
1g
1h
60 (120)
80 (80)
Pd(OAc)2
120 K3PO4 74 7400 3700
a
b
a
b
17
None
Pd(OAc)
none
2
60
30
30
K
3
PO
K3PO4
PO
4
5
0
500 500
2
5
NO
2
30 (60)
85 (80)
1
19
20
8
1a(0.01)
1a (0.01)
1a (0.01)
0
0
a
d
Under infrared irradiation using an Osram lamp (bulb model Thera-Therm,
Pd(OAc)
2
K
3
4
98 9800 19600
e
2
50 W, 125 V). For controlling the temperature, a Digi-Sense variable-time
Pd(OAc)2
300 K3PO4 90 9000 1800
b
a
power controller was used. Under conventional heating
All reactions were performed with p-iodotoluene (4b) (2 mmol), methyl
acrylate (5) (3.3 mmol), DMF (5 mL), base (2.5 mmol). T = 140 °C under
infrared irradiation using an Osram lamp (bulb model Thera-Therm, 250 W,
According with the results showed in Table 1, the use of IR allows
the reduction of the reaction time compared with conventional 125 V). For controlling the temperature, a Digi-Sense variable-time power
b
heating, particularly, when electron-withdrawing groups are controller was used.. Time reaction based on total consumption of aryl
c
iodide determined by TLC. Isolated yields after extraction with hexane.
included in phenylhydrazone (3) (Table 1, entries 3, 4, and 8).
d
e
2
Preparing separately the [Pd(AcO) /1a] catalyst system. Employing heating
blanket.
The compounds 1a-h were fully characterized by conventional
1
13
spectroscopic methods, FT-IR, H-NMR, C-NMR and mass spectra.
With these results, we found the following optimized conditions:
Pd(AcO) /1a] system 0.01% mol, in DMF with K PO at 140 °C for
0 minutes using infrared irradiation (IR) as an energy source.
[
2
3
4
Once efficiently prepared the compounds 1a-h, we explored as
catalytic precursors in the Heck cross-coupling reaction (Table 2).
The effect of concentration of the catalytic system on the Heck
reaction between methyl acrylate (5) and p-iodotoluene(4) under IR
heating condition was evaluate. We chose the hydrazone 1a and
3
In order to know the molecular structure of the formed complex by
the reaction between the hydrazone la and Pd(OAc) , we have
2
conducted some experiments in different reaction conditions,
observing in all cases the total consumption of the ligand, however ,
it was not possible to isolate these reaction product in neither case.
In our experience, we believe that hydrazone behaves as [N,N]
Pd(AcO)
under reflux of DMF (5 mL), using different concentrations of the
Pd(AcO) /1a] system. Good yields were obtained within 30
minutes, when 0.01 and 0.05 % mol of [Pd(AcO) /1a] was used
Table 2, entries 1, 2). The base influence was also evaluated and
employed different salts as K PO , Na CO , Na PO , K CO and
AcOK. We afforded 6b with a good yield (Table 2, entry 2).
2
as model precatalysts. The coupling reaction was stirred
[
2
2
ligand, as in other structurally similar hydrazone ligands we have
(
43,44
detected.
Thus, we conducted three additional experiments, the
and,
, we observe the formation
3
4
2
3
3
4
2
3
first one in absence of ligand, other one in absence of Pd(OAc)
as expected, only in the case of Pd(OAc)
2
2
of the coupling product but in low yield (Table 2, entries 17 and 18).
In the last experiment, we carried out the preformation of the
catalytic system and we observe a change of color and total
consumption of the ligand. After that, we added the substrates and
It is important to remark that all the compounds (1a-h) evaluated
are effective for the Heck reaction (entries 10-16), where hydrazone
1a provides a better yields in comparison to other compounds, with
2
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 7
PleaseRd So Cn oA t da vd aj un s ct ems argins
View Article Online
DOI: 10.1039/C5RA12715G
Journal Name
ARTICLE
base and the reaction was put in reflux under infrared irradiation. In Finally, we studied the effect of several aryl bromides 7a-f in the
this reaction condition, we obtained a similar yield of the coupling Heck reaction using methyl acrylate (5) (Table 5). Using p-
product (entry 19, Table 2), showing that the preformation of the substituted aryl bromides 7a-c with electron-donor groups, we
palladium complex does not affect the C-C coupling reaction.
obtained good yields of 6a-c (Table 5, entries 2, and 3). However,
moderate yields were obtained using p-substituted aryl bromides
For to compare the energy sources, we made an experiment under
the same reaction conditions described in Table 2, using
conventional heating (entry 20), and this results showed a dramatic
decreased time of reaction with the use of IR.
6
d-f with electron-withdrawing groups (Table 5, entries 4-7).
Table 4. Optimization of the reaction conditions on the Heck
a
reaction of p-bromotoluene (7a) with 5 .
2
To evaluate the scope of [Pd(AcO) /1a] as a catalytic system in the
Heck coupling reaction, a variety of activated and deactivated aryl
iodides and methyl acrylate was examined using this catalytic
system with the optimized condition reactions (Table 3). The results
2
show that the [Pd(AcO) /1a] system is an active and efficient
[
Pd(AcO) / 1a] (%
Time
Yield
(%)
2
Entry
TBAB
b
c
catalyst in the Heck coupling reaction producing good and
mol)
0.01
0.05
0.1
0.1
0.1
0.5
1
(min)
420
180
150
180
270
150
60
moderate yields of the corresponding coupling product 6a-g.
1
2
3
4
5
6
0
N.R.
N.R
Traces
10
Table 3. Scope of the Heck cross-coupling using aril iodides and the
a
20
20
40
50
50
50
2
[Pd(AcO) / 1a] system.
33
50
Time
Yield
7
90
Entry
R
TON
TOF
b
Product
4a
c
(
min)
(%)
a
All reactions were performed with p-bromotoulene 4a (2 mmol), methyl
PO (2.5 mmol). T = 140 °C under
infrared irradiation using an Osram lamp (bulb model Thera-Therm, 250 W,
25 V). For controlling the temperature, a Digi-Sense variable-time power
1
2
H
60
95
9500
9500
acrylate (5) (3.3 mmol), DMF (5 mL), K
3
4
1
CH
3
30
4b
98
9800 19600
b
controller was used. Time reaction based on total consumption of p-
bromotoulene 7b determined by TLC. Isolated yields after extraction with
c
3
4
5
6
OCH3
Br
60
90
4c
4d
4e
4f
97
70
50
70
70
9700
7000
5000
7000
7000
9700
4666
1666
3500
3500
hexane.
Table 5. Scope of Heck cross-coupling using aryl bromides 7a-f and
a
COCH
3
180
120
120
the [Pd(AcO) / 1a] system.
2
OCOCH
3
7
NO
2
4g
a
All reactions were performed with aryl Iodides 4a-g (2 mmol), methyl
PO (2.5 mmol), [Pd(AcO) /1a] = 0.01
mol. T = 140 °C under infrared irradiation using an Osram lamp (bulb
acrylate (5) (3.3 mmol), DMF (5 mL), K
3
4
2
%
Time
Yield
model Thera-Therm, 250 W, 125 V). For controlling the temperature, a Digi-
b
Entry
R
Product
TON
TOF
Sense variable-time power controller was used. Time reaction based on
b
c
c
(min)
(%)
total consumption of aryl iodide determined by TLC. Isolated yields after
2
extraction with hexane and SiO column chromatography.
1
2
3
4
5
H
CH3
OCH
Cl
90
6a
6b
6c
6d
6e
6f
70
85
90
80
50
50
7000
8500
9000
8000
5000
5000
4666
8500
Under similar conditions, the cross-coupling reaction was carried
out with p-bromotoluene 7b and methyl acrylate (5), which
provided methyl trans-cinnamate 6b, unfortunately the reaction did
not proceed (Table 4, entry 1). Consequently, we attempted to re-
optimize the conditions for the coupling of p-bromotoluene (7b)
and methyl acrylate (5) (Table 4).
60
3
180
45
3000
10666
5000
COCH
NO
3
60
6
2
30
10000
When 0.1 % mol of the [Pd(AcO) /1a] system and 40% mol of TBAB
2
a
All reactions were performed with p-iodotoulene 7a-f (2 mmol), methyl
PO (2.5 mmol), [Pd(AcO) /1a] = 1 %
were used, a small amount of the Heck reaction product was
obtained (Table 4, entry 4). After increasing the concentration of
acrylate (5) (3.3 mmol), DMF (5 mL), K
mol, 50 % mol TBAB. T = 140 °C under infrared irradiation using an Osram
lamp (bulb model Thera-Therm, 250 W, 125 V). For controlling the
3
4
2
the [Pd(AcO) /1a] system to 1 % mol and adding 50 % mol TBAB,
2
b
temperature, a Digi-Sense variable-time power controller was used. Time
the reaction produced good yields of 6b in 1h. (Table 4, entry 7).
reaction based on total consumption of aryl iodide 7a-f determined by TLC.
c
Isolated yields after purification by column chromatography with SiO
eluted with hexane.
2
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 4 of 7
View Article Online
DOI: 10.1039/C5RA12715G
ARTICLE
Journal Name
In attempt to extend this methodology to aryl chlorides, we also
conducted some experiments using p-chlorotoluene and p-
nitrochlorobenzene in the optimized conditions for aryl bromides,
but unfortunately, the corresponding coupling products were not
detected.
(
Z)-1-(2-Phenyl-2-(phenylhydrazono)ethyl)piperidine
1a.
This
compound was obtained in a pure way in 92 % yield as a yellow
+
solid. Mp.: 90-91 °C. MS-IE+ m/z (rel. intensity %): 293 [M ] (55),
Experimental
+
+
-1
2
1
6
1
1
01[C13
H
17
N
2
] (60), 98[C
6
H
12N] (100). Select IR νmax/cm (KBr):
General
597 (C=N), 1515 (CAr=CAr). δ
H
(300 MHz; CDCl ;Me Si) 1.50-1.64 (m,
3
4
H, H-b, H-b´ y H-c), 2.5 (m, 4H, H-a, H-a´), 3.69 (s, 2H, H-d), 6.84 (d,
H, H-n, JHnHm = 6.9 Hz), 7.15 (d, 2H, H-l, H-l´ JHlHm = 7.5 Hz), 7.25 (dd,
H, H-m, JHmHn = 6.9 Hz, JHmHl = 7.5Hz), 7.30-7.37 (m, 4H, H-h, H-h´
All operations were carried out in open atmosphere. Column
chromatographies were performed using 70–230 mesh silicagel. All
reagents and solvents were obtained from commercial suppliers
and used without further purification. All compounds were
characterized by IR spectra, recorded on a Perkin-Elmer 283B or
and H-i), 7.77 (d, 2H, H-g, H-g´) y 11.45 (s, 1H, H-j). δ
CDCl ;Me Si) 24.0 (C-c), 26.3 (C-b, C-b´), 53.7 (C-a, C-a´), 53.7 (C-d),
12.7 (C-l, C-l´), 119.5 (C-n), 125.5 (C-g, C-g´), 127.4 (C-i), 128.2 (C-h,
C-h´), 129.1 (C-m, C-m´), 139.0 (C-f), 139.5 (C-k) y 145.7 (C-e).
C
(75 MHz;
3
4
1
1420 spectrophotometer, by means of film and KBr techniques,
-1
and all data are expressed in wave numbers (cm ). Melting points
were obtained on a Melt- Temp II apparatus and are uncorrected.
NMR spectra were measured with a VARIAN +300 MHz, using CDCl
3
as solvent. Chemical shifts are in ppm (δ), relative to TMS. The MS-
EI spectra were obtained on a JEOL SX 102A, the values of the
signals are expressed in mass/charge units (m/z), followed by the
relative intensity with reference to a 100% base peak.
(
Z)-1-(2-(p-Metoxyphenyl)-2-(phenylhydrazono)ethyl)piperidine.
b. Yellow solid in 80%. Yield. Mp.: 68-70 °C. MS-IE+ m/z (rel.
1
+
+
+
intensity %): 323 [M] (28), 231 [C14
H
19
-1
N
2
O] (27), 133[C
12N] (100). Select IR νmax/cm (KBr): 1601.25 (C=N), 1504.57
Ar=CAr). δ (300 MHz; CDCl ;Me Si) 1.57-1.61 (m, 6H, H-b, H-b´ y H-
c), 2.46 (m, 4H, H-a, H-a´), 3.62 (s, 2H, H-d), 3.79 (s, 3H, OCH ), 6.87
and 7.69 (2d, 4H, H-g, H-g´ and H-h, H-h´, JHgHh = 9 Hz), 7.10-7.12 (m,
H, H-l, H-l´ and H-n), 7.22-7.27 (m, 2H, H-m, H-m´), 11.27 (s, 1H, H-
j). δ (75 MHz; CDCl ;Me Si) 24.0 (C-c), 26.2 (C-b, C-b´), 53.7 (C-a, C-
a´), 55.2 (C-OCH3), 57.2 (C-d), 112.6 (C-l, C-l´), 113.6 (C-g, C-g´),
19.2 (C-n), 126.8 (C-h, C-h´), 129.0 (C-m, C-m´), 131.9 (C-f), 139.6
8 9 2
H N ] (60),
IR equipment
+
9
6
8 [C H
The equipment used for irradiation with IR energy was created by
employing an empty cylindrical metal vessel in which an Osram
(
C
H
3
4
3
27
lamp (bulb model Thera-Therm, 250 W, 125 V) was inserted. This
lamp is special short-wave IR lamp (IR-A) for use in body care and
wellness applications, with a maximum radiation at a wavelength of
3
C
3
4
1100 nm. The lamp instantly emits a full thermal output as soon as
it is switched on. For controlling the temperature, a Digi-Sense
variable-time power controller was used. This time controller
turned the output load on and off and then repeated the cycle.
Although all the reactions were performed in open atmosphere,
this arrangement also allows the use of inert conditions.
1
(
C-k), 145.9 (C-e) y 159.2 (C-i).
General
procedure
for
the
synthesis
of
(Z)-
(
Z)-1-(2-(p-Chlorophenyl)-2-(phenylhydrazono)ethyl)piperidine. 1c.
(aminomethyl)(aryl)phenylhydrazones 1a-h.
This compound was obtained in a pure way in 90 % yield as a yellow
A mixture of 1 equivalent of phenylhydrazone (3), 2 equivalent of
formaldehyde (in a 37 % aqueous solution), and 2 equivalent of
secondary amine (piperydine or diethylamine) was irradiated using
an Osram lamp (bulb model Thera-Therm, 250 W, 125 V) at reflux
and stirred for the time stated in table 1.
+
solid. Mp: 72-74. MS-IE+ m/z (rel. intensity %): 327 [M] (10), 235
+
+
+
[
C
13
H
16
N
2
-1
Cl] (20), 98 [C
6
H
12N] (100), 84[C
max/cm (KBr): 1600 (C=N), 1491 (CAr=CAr).
;Me Si) 1.53-1.63 (m, 5H, H-b, H-b´ y H-c), 2.63 (m, 4H, H-a, H-
5
H
10N] (32). Select IR
ν
CDCl
H
δ (300 MHz;
3
4
a´), 3.65 (s, 2H, H-d), 6.85 (d, 1H, H-n), 7.14 and 7.69 (2d, 4H, H-g, H-
The reaction mixture was poured into water (15 mL) and extracted
with ether (3 x 15 mL). The combined organic layers were washed
with water (3 X 15 mL) and dried over anhydrous sodium sulfate.
The crude product was finally purified by flash column
chromatography on silica gel using hexane as an eluent to give the
corresponding isolated products.
g´, H-h, H-h´, JHgHh = 8.7 Hz), 7.25-7.32 (m, 4H, H-l, H-l´, H-m, H-m´),
1
C 3 4
1.43 (s, 1H, H-j). δ (75 MHz; CDCl ;Me Si) 23.9 (C-c), 25.8 (C-b, C-
b´), 53.7 (C-a, C-a´), 57.1 (C-d), 112.8 (C-l, C-l´), 119.7 (C-n), 126.6 (C-
h, C-h´), 128.3 (C-g, C-g´), 129.1 (C-m, C-m´), 133.2 (C-k), 137.5 (C-i),
1
38.1 (C-f) y 145.4 (C-e).
The starting phenylhydrazones (1) were prepared from
phenylhydrazine
with
various
5
commercially
available
4
benzaldehydes in methanol.
(
Z)-1-(2-(p-Nitrophenyl)-2-(phenylhydrazono)ethyl)piperidine. 1d.
This compound was obtained in a pure way in 99 % yield as an
orange solid. Mp: 140-141 °C. MS-IE+ m/z (rel. intensity %): 338
4
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 7
PleaseRd So Cn oA t da vd aj un s ct ems argins
View Article Online
DOI: 10.1039/C5RA12715G
Journal Name
ARTICLE
+
+
+
[
[
(
M] (47), 246 [C13
H
16
N
3
O
2
]
(38), 105[C
6
H
5
N
2
]
(30), 98 MHz; CDCl
3
;Me
4
Si) 1.07 (t, 6H, H-a, H-a’, JHaHb = 6.9 Hz), 2.54 (q, 4H,
+
+
+
-1
C
6
H
12N] (100), 84 [C
KBr): 1595 (C=N), 1514 (CAr=CAr), 1542, 1337 (N=O). δ
;Me Si) 1.48-1.52 (m, 5H, H-b, H-b´ y H-c), 2.46 (m, 4H, H-a, H-
a´), 3.67 (s, 2H, H-d), 6.87 (d, 1H, H-n, JHnHm = 4.5 Hz), 7.13 (dd, 2H, Hz), 11.42 (s, 1H, H-i). δ
H-m, H-m´, JHmHn = 4.5 Hz, JHmHl = 5.1 Hz), 7.27 (d, 2H, H-l, H-l´, JHlHm (C-b, C-b’), 52.3 (C-c), 112.7 (C-k, C-k’), 119.7 (C-m), 126.5 (C-f, C-f’),
.1 Hz), 7.85 and 8.14 (2d, 4H, H-g, H-g´, H-h, H-h´ JHgHh = 7.2 Hz), 128.3 (C-l, C-l’), 129.1 (C-g, C-g’), 133.8 (C-h), 137.4 (C-j), 138.7 (C-
1.75 (s, 1H, H-j). δ (75 MHz; CDCl ;Me Si) 23.9 (C-c), 25.8 (C-b, C- d), 145.4 (C-e).
6
H
10N] (58), 77 [C
6
H
5
] (56). Select IR νmax/cm
(300 MHz; 8.4 Hz), 7.06 (d, 2H, H-k, JHkHl = 6.6 Hz), 7.22 (dd, 2H, H-l, JHlHm = 8.4,
HlHk = 6.6 Hz), 7.27 and 7.64 (2d, 4H, H-g, Hg’ and H-f, Hf’, J = 9.0
(75 MHz; CDCl ;Me Si) 12.0 (C-a, C-a’), 46.9
H-b, H-b’ JHbHa = 6.9 Hz), 3.69 (s, 2H, H-c), 6.80 (d, 1H, H-m, JHmHl =
H
CDCl
3
4
J
C
3
4
=
5
1
C
3
4
b´), 53.0 (C-a, C-a´), 56.8 (C-d), 113.1 (C-l, C-l´), 120.7 (C-n), 123.6 (C-
h, C-h´), 125.4 (C-g, C-g´), 129.2 (C-m, C-m´), 136.1 (C-k), 144.7 (C-e),
145.0 (C-f) y 146.4 (C-i).
(
Z)-N,N-Diethyl-2-(p-nitrophenyl)-2-(2-
phenylhydrazono)ethanamine. 1f. Orange oil in 85 % yield. MS-IE+
+
.
+
m/z (rel. intensity %): 326 [M] (35), 281 [C H N O] (50), 234
1
8 23 3
+
+
+
(
Z)-N,N-Diethyl-2-phenyl-2-(2-phenylhydrazono)ethanamine. 1e. [C H N O ] (30), 105 [C H N ] (85), 86 [C H N] (100), 77 [C H ]
12 16 3 2 6 5 2 5 12 6 5
+.
-1
3
2
Yellow oil in 70 % yield. MS-IE+ m/z (rel. intensity %): 281 [M] .(60), (95). Select IR νmax/cm (KBr): 2931, 2968 (H-Csp , H-Csp ), 1593
+
+
+
2
09 [C14
H
13
N
2
] (20), 189 [C12
17
H N
2
] (60), 86[C
5
H
12N] (100). Select (C=N), 1544, (C =C ), 1490, 1331 (N=O), 1407 (CH ), 1384 (CH ).
Ar
Ar
2
3
-1
3
2
IR νmax/cm (KBr): 2817, 2932, 2968 (H-Csp ), 3023, 3056, (H-Csp ), δ (300 MHz; CDCl ;Me Si) 1.06 (t, 6H, H-a, H-a’, J
= 6.9 Hz), 2.53
HaHb
H
3
4
1
599 (C=N), 1556, 1491, (CAr=CAr), 1443 (CH
MHz; CDCl ;Me Si) 1.11 (t, 6H, H-a, H-a’ JHaHb = 6.9 Hz), 2.6 (q, 4H, H- JHmHl = 6.6 Hz), 7.06 (d, 2H, H-k, H-k’, JHkHl = 8.4 Hz), 7.22 (dd, 2H, H-l,
b, H-b’, JHbHa = 6.9 Hz), 3.77 (s, 2H, H-c), 6.83 (d, 1H, H-m, J = 7.8 Hz), H-l’, JHlHm = 6.6 Hz, JHlHk = 8.4 Hz), 7.83 and 8.12 (2d, 4H, H-g, H-g’
2
), 1384 (CH
3
H
). δ (300 (q, 4H, H-b, H-b’, JHbHa = 6.9 Hz), 3.74 (s, 2H, H-c), 6.83 (d, 1H, H-m,
3
4
7
.14 (d, 2H, H-k, H-k’, J = 8.1 Hz), 7.24-7.37 (m, 5H, H-l, H-I’, H-g, H- and H-f, H-f’, J = 9.3 Hz), 11.79 (s, 1H, H-i). δ (75 MHz; CDCl ;Me Si)
C
3
4
C 3 4
g’, H-h), 7.77 (d 2H, H-f, H-f’, J = 8.1 Hz). δ (75 MHz; CDCl ;Me Si) 11.9 (C-a, C-a’), 46.8 (C-b, C-b’), 52.0 (C-c), 1131 (C-k, C-k’), 120.6 (C-
12.0 (C-a, C-a’), 46.9 (C-b, C-b’), 52.5 (C-c), 112.7 (C-k, C-k’), 119.4 m), 123.7 (C-g, C-g’), 125.3 (C-f, C-f’), 129.2 (C-l, C-l’), 136.6 (C-j),
(C-m), 125.4 (C-f, C-f’), 127.4 (C-h), 128.2 (C-l, C-l’), 129.1 (C-g, C-g’), 144.6 (C-d), 145.0 (C-e), 146.3 (C-h).
139.0 (C-d), 140.0 (C-j), 145.6 (C-e).
General procedure for Mizoroki–Heck coupling reactions
In a 50-mL round-bottomed flask, a mixture of aryl halide (2 mmol),
methyl acrylate (3.3 mmol), and the corresponding base (2.5
mmol), was placed in 5 mL of DMF, then the source of palladium
and the corresponding hydrazone 1 were added (see Tables 2-5).
The reaction mixture was irradiated using an Osram lamp (bulb
model Thera-Therm, 250 W, 125 V) for the time stated in tables 2-5
at 140 °C. The reaction mixture was poured into water (10 mL) and
extracted with ether or hexane (3 X 10 mL). The combined organic
layers were dried over anhydrous sodium sulfate.
(
Z)-N,N-Diethyl-2-(p-metoxiphenyl)-2-(2-
phenylhydrazono)ethanamine. 1f. Yellow oil in 80 % yield. MS-IE+
+
+
m/z (rel. intensity %): 311 [M] (80), 281 [C18
H
23
+
N
3
]
(25), 239
+
+
[C
15
H
15
N
2
O] (20), 133 [C
9
H
9
O] (100), 86 [C
5
H
12N] (90). Select IR
-1
3
2
ν
1
max/cm (KBr): 2835 (H-Csp ), 2932, 2966, (H-Csp ), 1599 (C=N),
503, 1463, (CAr=CAr), 1440 (CH
2
), 1384 (CH
3
). δ
H
(300 MHz;
CDCl
3
;Me Si) 1.11 (t, 6H, H-a, H-a’, JHaHb = 7.2 Hz), 2.59 (q, 4H, H-b, The crude product was finally purified by flash column
4
H-b’, JHbHa = 7.2 Hz), 3.74 (s, 2H, H-c), 6.81 (d, 1H, H-m, JHmHl = 8.1 chromatography on silica-gel to give the isolated products in yields
Hz), 6.89 (d, 2H, H-k, H-k’, JHkHl = 8.7 Hz), 7.27 (dd, 2H, H-l, H-l’, JHlHm stated in the tables 2-5. The purified product was identified by
1
13
=
8.1 Hz, JHlHk = 8.7 Hz ), 7.11 and 7.70 (2d, 4H, H-g, H-g’ and H-f, Hf’ means of determination of mp and by H and C NMR, the data
4
6
C 3 4
J = 9 Hz), 11.31 (s, 1H, H-i). δ (75 MHz; CDCl ;Me Si) 12.2 (C-a, C-a’), obtained are consistent with literature.
4
7.0 (C-b, C-b’), 52.6 (C-c), 112.7 (C-g, C-g’), 113.8 (C-k, C-k’), 119.3
Note: The entire round flasks used in each coupling reaction were
meticulously cleaned with aqua regia to avoid the presence of
unseen palladium catalyst.
(C-m), 126.9 (C-f, C-f’), 129.2 (C-l, Cl’), 132.0 (C-d), 140.4 (C-j), 139.0
C-d), 146.0 (C-e), 159.4 (C-h).
(
Conclusions
We
describe
the
synthesis
of
new
(Z)-
(
Z)-N,N-Diethyl-2-(p-chlorophenyl)-2-(2-
(
aminomethyl)(aryl)phenylhydrazones (1a-h) with good yields via
phenylhydrazono)ethanamine. 1g. Yellow oil in 80% yield. MS-IE+
the Mannich coupling reaction using IR as a source energy and
+
+
m/z (rel. intensity %): 315 [M] (60), 223 [C12
H
16ClN
2
] (45), 137
] (50).
solvent-free conditions. These new hydrazones 1a-h are promising
+
+
+
[
C
8
H
6
Cl] (63), 105 [C
6
H
5
N
2
] (65), 86 [C
Select IR νmax/cm (KBr): 2819, 2932, 2968 (H-Csp ,H-Csp ), 1599
C=N), 1574, 1548, 1488, (CAr=CAr), 1400 (CH ), 1384 (CH ). δ (300
5
H
12N] (100), 77 [C H
6 5
2
for the catalysis of Heck coupling reactions using IR and Pd(AcO)
2
.
-1
3
Particularly, the [Pd(AcO) /1a] system showed to be a good
2
(
2
3
H
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 6 of 7
View Article Online
DOI: 10.1039/C5RA12715G
ARTICLE
Journal Name
catalyst in this reaction, being more active when electron-rich aryl
halide are used as substrates.
Phan, M. C. Van Der Sluys and W. Jones, Adv. Synth. Catal.,
006, 348, 609-679.
1. K.-S. Masters and B. L Flynn, Org. Biomol. Chem., 2010, 8, 1290-
1292.
2. (a) Metal-Catalyzed Cross-Coupling Reactions, ed. A. de Meijer
and F. Diederich, Wiley-VCH, Weinheim, 2004; (b) A. Zapf and
M.Beller, Top. Catal., 2002, 19, 101-109; (c) C.E. Tucker and J. G.
de Vries, Top. Catal., 2002, 19, 111-118.
2
1
1
As we have described, the use of infrared as energy source favors
the Mannich and Heck coupling reactions to obtain the
corresponding products in an efficient manner. The reaction times
decrease in all the cases, in comparison to experiments conducted
in conductive heating. Thus, infrared irradiation effectively 13. (a) K. Temburnikar, K. Brace and K. L. Seley-Radtke, J. Org.
penetrates the reaction vessel and causes a sudden increase in
temperature, which allows to easily reach the activation energy to
transform substrates into products.
Chem., 2013, 78, 7305-7311. (b) A. C Häberli, and J. Leumann,
Org. Lett., 2001, 3, 489-492.
4. Z. Feng, Q.-Q. Min, H.-Y. Zhao, J.-W. Gu, and X. Zhang, Angew.
Chem. Int. Ed., 2014, 53, 1–6.
5. (a) B. Marudai, Palladium in Heterocyclic Chemistry in
Tetrahedron Organic Chemistry Series, ed. J. Jack Li and G. W.
Gribble, Elsevier, Netherlands, 2th edition, 2007, vol 26,
Chapter 14, 587-620. (b) H.-U. Blaser, A. Indolese, F. Naud, U.
Nettekoven and A. Schnyder, Adv. Synth. Catal., 2004, 346,
1
1
Therefore, we evidence that infrared irradiation (IR) is an efficient,
economical and accessible alternative source of energy to assist
both, the synthesis of (Z)-(aminomethyl)(aryl)phenylhydrazones,
and Heck coupling reactions.
1
583-1598.
1
6. (a) M. Hoyos, D. Guest, O. Navarro in N-Heterocyclic Carbenes,
S. P. Nolan Ed. Wiley-VCH, Weinheim, 2014 Ch.4, pp 85-109.
Acknowledgements
(
1
b)N. Marion and S. P. Nolan, Acc. Chem. Res., 2008, 41, 1440-
449.
The authors would like to acknowledge the technical
assistance provided by Luis Velasco and Javier Pérez. The
authors also thank CONACYT 153059 and Facultad de Estudios
Superiores Cuautitlán PIAPIC14 projects.
1
1
1
7. W. A. Herrmann, K. Ofele, S.K. Schneider, E. Herdtweck and
Hoffmann, S. D. Angew. Chem., Int. Ed., 2006, 45, 3859-3862.
8. Q. Yao, M. Zabawa, J. Woo and Zheng, C. J. Am. Chem. Soc.,
2
007, 129, 3088-3089.
9. (a) K.-M. Wu, C.-A. Huang, K.-F. Peng and C.-T. Chen,
Tetrahedron, 2005, 61, 9679-9687. (b) K. Mustafa, K. Hülya, E.
Duygu Melis, Appl. Organomet. Chem. 2015, 29, 543-548.
0. C. Najera, J. Gil-Moito, S. Karlstrum, and L.R. Falvello, Org. Lett.,
2
RSC Adv., 2015, 5, 19630–19637
1. K. Kawamura, S. Haneda, Z. Gan, K. Eda and M. Hayashi,
Organometallics, 2008, 27, 3748-3752.
2. (a) V. Montoya, J. Pons, V. Branchadell, J. Garcia-Antón, X.
Solans, M. Font-Bardía, and J. Ros, Organometallics, 2008, 27,
1084-1091; (b) F. Li and T. S. A. Hor, Adv. Synth. Catal., 2008,
350, 2391-2400.
References
1
.
.
(a) E. F. Kleinman, In Comprehensive Organic Synthesis, Trost, B.
M., Fleming, I., Eds., Pergamon, Oxford, 1991; Vol. 2, pp 893–
2
895; (b) N. Risch, M. Arend and B. Westermann, Angew. Chem.
003, 5, 1451-1454. S.M. Sarkar, M. L. Rahman, M. M. Yusof.
Ind. Ed., 1998, 37, 1044–1070; (c) W. N. Speckamp and M. J.
Moolenaar, Tetrahedron, 2000, 56, 3817–3856.
(a) G. Keil and W. Ried, Liebigs Ann. Chem., 1957, 605, 167-179;
2
2
2
(b) V. Atlan, H. Bienaymé, L. El Kaïm and A. Majee, Chem.
Commun., 2000, 1585–1586; (c) L. El Kaïm,a L. Gautier,a L.
Grimaud,a L. M. Harwoodb and V. Michauta, Green Chem.,
2003, 5, 477–479; (d) V. Atlan, L. El Kaïm, L. Grimaud, N. K. Jana
and A. Majee, Synlett, 2002, 352–354.
3.
4.
5.
K. Inamoto, M. Katsuno, T. Yoshino, Y. Arai, K. Hiroya and T. 23. S. Lee, J. Organomet. Chem., 2006, 691, 1347-1355.
Sakamoto, Tetrahedron, 2007, 63, 2695-2711.
N. Ghavtadze, R. Frohlich and E.-U. Wurthwein, Eur. J. Org.
Chem., 2008, 3656-3667.
(a) P.Barbazan, R. Carballo, B. Covelo, C. Lodeiro, J. C. Lima and
E. M. Vázquez-López, Eur. J. Inorg. Chem., 2008, 2713-2720; (b)
S. Banerjee, S. Mondal, W. Chakraborty, S. Sen, R. Gachhui, R. J.
Butcher, A. M. Z. Slawin, C. Mandal and S. Mitra, Polyhedron,
2
2
4. (a) T. Mino, M. Shibuya, S. Suzuki, K. Hirai, M. Sakamoto, T.
Fujita. Tetrahedron 2012, 68, 429-432. (b) T. Mino, H. Shindo, T.
Kaneda, T. Koizumi, Y. Kasashima, M. Sakamoto, T. Fujita.
Tetrahedron Lett., 2009, 50, 5358–5360. (c) T. Mino, Y. Shirae,
M. Sakamoto and T. Fujita, J. Org. Chem., 2006, 71, 6834-6839
5. (a) Q. Yao, E.P. Kinney, and C. Zheng, Org. Lett. 2004, 6, 2997-
2
999. (b) T. Chakraborty, K. Srivastava, H. B. Singh, R. J. Butcher.
2009, 28, 2785-2793.
6
.
.
(a) T. Mino, Y. Shirae, Y. Sasai, M. Sakamoto and T. Fujita, J.
Org. Chem., 2006, 71, 6834-6839; (b) T. Mino, H. Shindo, T.
Kaneda, T. Koizumi, Y. Kasashima, M. Sakamoto and T. Fujita,
Tetrahedron Lett., 2009, 50, 5358-5360.
J. Organomet. Chem.2011, 696, 2559-2564
26. X. Cui, Y. Zhou, N. Wang, L. Liu, and Q.-X. Guo, Tetrahedron
Lett., 2007, 48, 163-167.
7. W. Chen, R. Li, B. Han, B.J. Li, Y.C. Chen, Y. Wu, L.S. Ding, and D.
Yang, Eur. J. Org. Chem. 2006, 1177-1184.
8. (a) J. Dupont, C. S. Consorti and J. Spencer, Chem. Rev. 2005,
2
7
(a) T. Mino, Y. Shirae, M. Sakamoto and T. Fujita, Synlett, 2003,
882-884; (b) T. Mino, Y. Shirae, M. Sakamoto and T. Fujita, J.
2
Org. Chem., 2005, 70, 2191-2194.
T. Mino, Y. Shirae, T. Saito, M. Sakamoto and T. Fujita, J. Org.
Chem. 2006, 71, 9499-9502
T. Mino, K. Kajiwara, Y. Shirae, M. Sakamoto and T. Fujita,
Synlett, 2008, 2711-2715.
1
4
05, 2527-2572. (b) Zapf, M. Beller. Chem. Commun., 2005,
31–440. (c) I. P. Beletskaya, A. V. Cheprakov. J. Organomet.
8
9
1
.
Chem. 2004, 689, 4055–4082
9. (a) C.M. Frech in Pincer and Pincer-type complexes, K. J. Szabó,
O.F. Wendt Ed. Wiley-VCH, Weinheim, 2014 Ch.10, pp 249-280
.
2
0. For some representative reviews, see: (a) W. A. Herrmann,
(
b) M. Hirotsu, Y. Tsukahara and I. Kinoshita, Bull. Chem. Soc.
V.P.W. Böhm and C.-P. Reisinger, J. Organomet. Chem., 1999,
5
76, 23-41; (b) I. P. Beletskaya and A. V Cheprakov, Chem. Rev.,
Jpn. 2010, 83, 1058-1066. (c) Q.-L. Luo, J.-P. Tan, Z.-F Li, Y. Qin,
L. Ma and D.-R. Xiao, Dalton Trans., 2011, 40, 3601-3609.
2000, 100, 3009-3066; (c) G. D. Daves and A. Hallberg, Chem.
Rev., 1989, 89, 1433-1445; (d) H. Li, C. C. Johansson-Seechurn 30. A. Balanta, C. Godard, and C. Claver, Chem. Soc. Rev. 2011, 40,
and T. J. Colacot, ACS Catal., 2012, 2, 1147-1164; (e) N. T. S.
4
973-4985.
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 7
PleaseRd So Cn oA t da vd aj un s ct ems argins
View Article Online
DOI: 10.1039/C5RA12715G
Journal Name
ARTICLE
3
3
3
1. J. Mondal, A. Modak, and A. Bhaumik. J. Mol. Catal. A: Chemical,
2011, 350, 40–48.
2. A. Modak, J. Mondal, V. K. Aswal, and A. Bhaumik. J. Mater.
Chem., 2010, 20, 8099–8106.
3. (a) C. O. Kappe, D. Dallinger and S. S. Murphree, Practical
Microwave Synthesis for Organic Chemists Strategies,
Instruments and Protocols, Wiley-VCH, Weinheim, 2009; (b) A.
Loupy, Microwaves in Organic Synthesis, Wiley-VCH, Weinheim,
2006. (c) M. Larhed and K. Olofsson, Microwave Methods in
Organic Synthesis, Springer, Berlin, 2006; (d) M. Larhed, C.
Moberg and A. Hallberg, Acc. Chem. Res., 2002, 35, 717-727.
4. (a) G. Cravotto and P. Cintas, Chem. Soc. Rev., 2006, 35, 180–
3
3
3
1
96; (b) F. M. Nowak, Sonochemistry: Theory, Reactions,
Syntheses, and Applications; Nova Science Publishers, New York,
011; (c) T.J. Mason, Chem. Soc. Rev., 1997, 26, 443-451.
5. (a) I.R. Baxendale, L. Brocken, C. J. Mallia, Green Process Synth.,
013, 2, 211-230; (b) R. Wladimir, Microreactors in Preparative
2
2
Chemistry: Practical Aspects in Bioprocessing, Nanotechnology,
Catalysis and More, Wiley-VCH, Weinheim, 2013.
6. (a) M.A. Vázquez, M. Landa, L. Reyes, R. Miranda, J. Tamariz and
F. Delgado, Synth. Commun., 2004, 34, 2705-2718; (b) G.
Alcerreca, R. Sanabria, R. Miranda, G. Arroyo, J. Tamariz and F.
Delgado, Synth. Commun., 2000, 30, 1295-1301; (c) M. Salmón,
R. Osnaya, L. Gómez, G. Arroyo, F. Delgado, R. Miranda, Rev.
Soc. Quim. Mex., 2001, 45, 206-207.
3
7. J. E. Valdez-Rojas, H. Ríos-Guerra, A. Ramírez-Sánchez, G.
García-González, C. Álvarez-Toledano, J. G. López-Cortés, R.A.
Toscano and J. G. Penieres-Carrillo, Can. J. Chem., 2012, 90, 567-
573.
38. (a) G. Penieres-Carrillo, J.G. García-Estrada, J.L. Gutiérrez-
Ramírez and C. Álvarez-Toledano, Green. Chem., 2003, 5, 337-
339; (b) G. Penieres, J.M. Aceves, A. Flores, G. Mendoza, O.
García and C. Álvarez, Heterocycl. Comm., 1997, 3, 507-508.
9. M.I. Flores-Conde, L. Reyes, R. Herrera, H. Ríos, M. A. Vázquez,
R. Miranda, J. Tamariz and F. Delgado, Int. J. Mol. Sci., 2012, 13,
3
2590-2617.
4
0. (a) P. Anastas and J. Warner, Green Chemistry: Theory and
Practice, University Press, Oxford, 1998; (b) J.M. DeSimone,
Science, 2002, 297, 799-803; (c) R.A. Gross and B. Kalra, Science,
2002, 297, 803-807; (d) M. Poliakoff, J.M. Fitzpatrick, T.R. Farren
and P.T. Anastas, Science, 2002, 297, 807-810.
4
1. (a) C. O. Kappe, Angew. Chem., Int. Ed. 2004, 43, 6250-6282; (b)
J. Thuery, Microwaves: Industrial, Scientific and Medical
Applications, Artech House, Boston, 1992.
4
4
2. D. E. Bergbreiter and S. Furyk, Green Chem, 2004, 6, 280-285.
3. F. Ortega-Jiménez, F.X. Domínguez-Villa, A. Rosas-Sánchez, G
Penieres-Carrillo, J.G. López-Cortés, M. C. Ortega-Alfaro. Appl.
Organomet. Chem. 2015, 29, 556-560.
44. (a) F. Ortega-Jiménez, E. Gómez, P. Sharma, M.C. Ortega-Alfaro,
R.A. Toscano, C. Alvarez-Toledano, C. Z. Anorg. All. Chem. 2002,
628, 2104-2108. (b) F. Ortega-Jiménez, J.G. López-Cortés, M.C.
Ortega-Alfaro, A. Toscano, G. Penieres, R. Quijada, C. Alvarez, J.
Organomet. Chem. 2005, 690, 454-462.
4
4
5. J, Buckingham. Q. Rev. Chem. Soc., 1969, 23, 37-56.
6. For NMR data of methyl 4-R-cinnamates, see: (a) R = MeO, Me,
H: C. Diebold, S. Schweizer, J.-M. Becht and C. Le Drian, Org.
Biomol. Chem., 2010, 8, 4834-4836; (b) R = Br, COOCH
FranÅois-Xavier, M. Karinne, S. Jean-Marc, F. Eric, I. Oier and L.
Julia, Chem. Eur. J., 2010, 16, 5191–5204; (c) R = NO : R. Bernini,
3
: F.
2
S. Cacchi, G. Fabrizi, G. Forte, S. Niembro, F. Petrucci, R. Pleixats,
A.Prastaro, R.M. Sebastia, R. Soler, M. Tristany and A. Vallribera,
Org. Lett., 2008, 4, 561–564; (d) R = Ac: M. Paul, F.B. John, K.C.
David, K.G. Ewan, S.P. Jeremy and B.S. Joseph, Org. Process Res.
Dev., 2013, 17, 397−405.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins