An efficient and simple imidazole-hydrazone ligand for palladium-catalyzed Suzuki-Miyaura cross-coupling reactions in water under infrared irradiation

Article abstract of DOI:10.1016/j.jorganchem.2018.11.016

A highly efficient catalytic system based on Pd(OAc)₂ and an imidazole-hydrazone ligand has been developed for Suzuki–Miyaura cross-coupling reaction in water under aerobic conditions using IR-irradiation. The system can tolerate a wide range of functionalized arylboronic acids and aryl halides. Furthermore, this protocol is also applicable for hetero-aryl bromides.

Full text of DOI:10.1016/j.jorganchem.2018.11.016

Accepted Manuscript
Imidazole-hydrazone efficient and simple ligand for palladium-catalyzed Suzuki-
Miyaura cross-coupling reaction in water under IR-irradiation
Martín Camacho-Espinoza, José Guillermo Penieres-Carrillo, Hulme Rios-Guerra,
Selene Lagunas-Rivera, Fernando Ortega-Jiménez
PII:
S0022-328X(18)30886-6
DOI:
https://doi.org/10.1016/j.jorganchem.2018.11.016
JOM 20636
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 9 October 2018
Revised Date: 8 November 2018
Accepted Date: 10 November 2018
Please cite this article as: Martí. Camacho-Espinoza, José.Guillermo. Penieres-Carrillo, H. Rios-
Guerra, S. Lagunas-Rivera, F. Ortega-Jiménez, Imidazole-hydrazone efficient and simple ligand for
palladium-catalyzed Suzuki-Miyaura cross-coupling reaction in water under IR-irradiation, Journal of
Organometallic Chemistry (2018), doi: https://doi.org/10.1016/j.jorganchem.2018.11.016.
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ACCEPTED MANUSCRIPT
Graphical Abstract
An efficient and simple imidazole-hydrazone ligand for palladium-catalyzed Suzuki-Miyaura
cross-coupling reactions in water under infrared irradiation
Martín Camacho-Espinoza, José Guillermo Penieres-Carrillo, Hulme Rios Guerra, Selene Lagunas-
Rivera, Fernando Ortega-Jiménez.*
Efficient catalytic system [imidazole-hydrazone (L1-L3)/Pd(OAc)2] has been developed for Suzuki–
Miyaura reaction in water under IR-irradiation. A wide range of substrates could be coupled with
phenylboronic acid to afford the desired products in good to excellent yields at low catalyst loadings
and low time of reaction.

ACCEPTED MANUSCRIPT
Imidazole-hydrazone efficient and simple ligand for palladium-catalyzed Suzuki-Miyaura
cross-coupling reaction in water under IR-irradiation
Martín Camacho-Espinoza,a José Guillermo Penieres-Carrillo,a Hulme Rios-Guerra,a Selene Lagunas-
Rivera,b Fernando Ortega-Jiménez.a*
aDepartamento de Ciencias Químicas, Facultad de Estudios Superiores Cuautitlán-UNAM, Campo 1,
Avenida 1ro. de Mayo s/n, Cuautitlán Izcalli, C.P. 54740, Estado de México, México. Tel.: +52-555-
623-2024; fax: +52-555-623-2024; E-mail: fdo.ortega@unam.mx.
bCatedra-CONACyT Departamento de Química Universidad de Guanajuato, Noria Alta S/N, C.P.
36050 Guanajuato, Guanajuato, México
Abstract
A highly efficient catalytic system based on Pd(OAc)2 and imidazole-hydrazone (L1-L3) has been
developed for Suzuki–Miyaura cross-coupling reaction in water under aerobic conditions using IR
irradiation. The system can tolerate a wide range of functionalized arylboronic acids and aryl halides.
Furthermore, this protocol is also applicable and available for hetero-aryl bromides.
Keywords. Imidazole-hydrazone, Palladium-catalyzed, Cross-coupling reaction, water, IR-irradiation
1. Introduction
The palladium catalyzed Suzuki–Miyaura reaction between organoboron compounds and organic
halides is one of the most powerful and convenient approaches for forming carbon–carbon bonds,
particularly for the synthesis of biaryls.[1] Owing to the fact that the aryl–aryl structure motif is an
important building block in organic chemistry, the Suzuki–Miyaura reaction is widely applied in
academic research as well as in industrial synthesis of fine chemicals and highly complex
pharmaceuticals.[2]
This application of the reaction results from the broad functional group tolerance, the commercial
availability and low toxicity of the organoborons, the mild reaction conditions, ease of handling of
products and by-products, and the possibility of using water as a solvent or co-solvent.[3,4]
The Suzuki–Miyaura cross-coupling reaction is usually catalyzed by a wide variety of Pd-based

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catalysts and the effectiveness of the catalytic system is dependent on the ligand environment around
palladium. In the traditional Suzuki–Miyaura reactions, the electron-rich phosphine ligands were
generally employed to improve the catalytic performance.[5] Since phosphine ligands are often water-
and air-sensitive,[6] catalysis under phosphine-free conditions is still a challenge of high importance,
different nitrogen based ligands such as N-heterocyclic carbenes,[7] palladacycle species,[8] N,O- or
N,N-bidentate ligands,[9] aryloximes,[10] O-aryloxime ether,[11] arylimines,[12] N-acylamidines,[13]
amines,[14] 2-aryl-2-oxazolines,[15] aylhydrazones,[16] among the others, have emerged as efficient
ligands for Suzuki–Miyaura reaction with the potential to overcome most of the drawbacks of
traditional phosphine ligands.
Additionally, the classic Suzuki–Miyaura reaction was often carried out in organic media, such as
DMF,[17] THF,[18] dioxane,[19] toluene,[20] CH3CN,[21] and methanol,[22]. Recently, this coupling
reaction has strongly benefited from aqueous media,[23] most of substrates used are insoluble in water
but numerous efforts have been made, such as synthesizing water-soluble ligands,[24] adding
surfactants and/or phase-transfer agents,[25] or using microwave[26] or ultrasound[27]. Yet, most
aqueous protocols for cross coupling reactions have some drawbacks such as high catalyst loading,[24b,
25d, 28] long reaction times[29] or require the addition of organic co-solvents, [30] including protocols
ligand-free[25d, 28, 30b]. From these standpoints, the development of efficient, stable, economical, and
environmentally friendly catalytic system remains a challenging task.
On the other hand, new alternative heating methodologies such as microwave,[31] ultrasound,[32] and
infrared (IR) irradiation[33] have been applied in organic synthesis and catalysis with reduced reaction
times, cleaner reaction mixtures and good yields. As a research program focused on the use of IR
irradiation in C-C coupling reactions, recently we explore the use of IR to assist the Mizoroki-Heck
[34,35] and Suzuki-Miyaura [36,37] cross-coupling reactions; in addition, we demonstrated an air
stable phosphine-free hydrazone containing a heterocycle moiety as an effective ligand for palladium
catalyzed Mizoroki-Heck[35,37] and Suzuki-Miyaura[37] cross-coupling under IR irradiation.
However, does not exist any papers about using arylhydrazones containing a heterocycle moiety as
ligands for the Suzuki–Miyaura reaction in water using IR irradiation as the energy source. Herein, we
report the synthesis of arylhydrazone derivatives containing the imidazole moiety as the effective
ligand for palladium-catalyzed Suzuki-Miyaura cross-coupling reactions in water using IR irradiation,
as an efficient, convenient, and environmentally friendly protocol for this cross-coupling reaction.

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2. Experimental
2.1. Apparatus, materials, and measurements
All operations were carried out in open atmosphere. Column chromatography was performed using 70–
230 mesh silica gel. All reagents and solvents were obtained from commercial suppliers and used
without further purification. All compounds were characterized by IR spectra, recorded with a Perkin-
Elmer 283B or 1420 spectrophotometer, by means of film and KBr techniques, and all data are
expressed in wavenumbers (cm-1). Melting points were obtained on a Melt- Temp II apparatus and are
uncorrected. NMR spectra were measured with a Varian Eclipse +300 using CDCl3 as solvents.
Chemical shifts are in ppm (δ), relative to TMS. The MS-EI spectra were obtained on a JEOL SX 102a,
the MS-DART spectra were obtained with a AccuTOF JMS-T100LC, 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.
The equipment used for irradiation with IR energy was created by employing an empty cylindrical
metal vessel in which an Osram lamp (bulb model Thera-Therm, 250 W, 125 V) was inserted.[34]
2.2.
General synthetic procedure for de compounds L1-L3.
A solution of the corresponding phenylhydrazine (1.8 mmol) in methanol (5 mL) was added dropwise
to a magnetically stirred solution of 1-methyl-2-imidazolcarbaldehyde (1.8 mmol) in methanol (5 mL).
The reaction mixture was refluxed using IR irradiation for 1.5 h, to give a yellow solid, which was
recovered by filtration and recrystallized from methanol.
1-methylimidazole-2-carbaldehyde N,N-diphenylhydrazone L1. (98 %) yellow crystals, mp 122-125 °C,
IR: ν (cm-1): 3138, 3024, 2957, 2925 y 2858, (H-Csp2 y H-Csp3), 1585 (C=N) y 1490 (C=Carom). MS-EI
(70 eV) m/z (%): 276 M+• (100), 167 [C12H9N]+ (50). 1H-NMR: (300 MHz, CDCl3) δ (ppm) 4.10 (s, 1H,
NCH3), 6.89 (s, 1H, H5imidazole), 7.00 (s, 1H, H4imidazole), 7.11 (d, J = 7.5 Hz, 4H, Harom o), 7.19 (t, J =
7.5 Hz, 2H, Harom p), 7.31 (s, 1H, HC=NNPh2), 7.41 (t, J = 7.5 Hz, 4H, Harom m). 13C-NMR: (75 MHz,
CDCl3) δ (ppm) 35.9 (NCH3), 122.2 (Carom o), 123.3 (C5imidazole), 124.7 (Carom p), 128.4 (C4imidazole),
129.0 (HC=NNPh2), 129.9 (Carom m), 142.7 (Cipso N), 143.4 (C2imidazole).
1-methylimidazole-2-carbaldehyde N-phenyl-N-methylhydrazone L2 (92 %) brown crystals mp. 84-
88°C. IR: ν (cm-1): 3124, 3028, 2958, 2925 y 2848, (H-Csp2 y H-Csp3), 1590 (C=N) y 1496 (C=C
aromático). EM-DART: m/z (%), 214 M+•, 163 [C9H13N3]+.1H-NMR: (300 MHz, CDCl3) δ (ppm) 3.30
(s, 1H, NCH3), 3.91 (s, 1H, NCH3imidazole), 6.78 (s, 1H, H5imidazole), 6.86 (t, J = 7.5 Hz, 2H, Harom p),

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13
6.97 (s, 1H, H4imidazole), 7.14-7.23 (m, 4H, Harom o,p), 7.50 (s, 1H, HC=NNPh2). C RMN: (75 MHz,
CDCl3) δ (ppm) 32.9 (NCH3), 36.0 (NCH3 imidazole), 115.2 (Carom o), 121.1 (Carom p ), 123.0 (C5imidazole),
124.7 (C4imidazole), 127.3 (HC=NNPh2), 129.1 (Carom m), 143.7 (Cipso N), 147.3 (C2imidazole).
1-methylimidazole-2-carbaldehyde N-phenylhydrazone L3. (90%) yellow crystals, mp. 68-72 °C. IR: ν (cm-
1): 3191, 3126, 3103, 3017, 2944, 2856 (H-Csp2 y H-Csp3), 1588 (C=N), 1490, 1461 (C=Carom). MS-EI: m/z (%), 200
1
M+.(100), 95 [C5H7N2]+ (30), 77 [C6H5]+ (15). H RMN: (300 MHz, CDCl3) δ (ppm) 3.86 (s, 1H, NCH3), 6.74-6.79
(m, 2H, H5imizole, Harom p), 6.90-6.95 (m, 3H, H4imizole, Harom o), 7.16 (t, 2H, J = 7.5 Hz, 2H, Harom m), 7.73 (s, 1H,
HC=NNPh2), 8.73 (s, 1H, N-H). RMN 13C: (75 MHz, CDCl3) δ (ppm) 35.6 (NCH3), 112.3 (Carom o), 119.8 (Carom p),
123.5 (C5imidazole), 128.5 (C4imidazole), 129.1 (Carom m), 129.4 (HC=NNPh2), 142.8 (Cipso N), 144.4 (C2imidazole).
2.3.
General procedure for Suzuki-Miyaura coupling reactions
Inside a 50-mL round-bottom flask, a mixture of aryl halide (0.5mmol), phenylboronic acid (0.6
mmol), and base (1 mmol) was placed in 3 mL of solvent; then Pd source and corresponding
arylhydrazone 1 were added. The reaction was irradiated with IR energy34-37 for the time reported in
Tables 1 and 2. Thereafter, the reaction was cooled at room temperature; the mixture was diluted with
10 mL of water and extracted with hexane or AcOEt (3 X 10 mL). The combined organic layers were
dried over anhydrous sodium sulfate. The crude product was finally purified by column
chromatography on silica-gel to give the isolated products.
1
13
The purified product was identified by means of mp determination and by H and C-NMR; the data
obtained are consistent with literature.[38]
3. Results and discussion
3.1.
Synthesis and characterization of hydrazones L1-L3.
The arylhydrazone ligands L1–L3 were prepared employing the condensation reaction of the
corresponding arylhydrazine and 1-metyl-2-imidazolcarbaldehyde in 1:1 mole ratio in methanol under
IR irradiation for 1.5 h (Scheme 1). After of crystallization of methanol the ligand L1-L3 was obtained
as a solid in a 98, 92 and 90 % yields respectively and were fully characterized by conventional
spectroscopic methods, 1H NMR, 13C NMR, IR and MS.

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Scheme 1. Synthesis of imidazole-hydrazone L1-L3.
The infrared spectra of L1-L3 show an absorption band in in a range between 1585-1588 cm-1, which is
assigned to the vibration of the νC=N bond, that indicated the arylhydrazone formation. The NMR and
mass spectra of compounds L1-L3 are found to be in agreement with their molecular structures. The
1
singlet signals of the H NMR spectra at 7.31 ppm, 7.50 ppm and 7.73 ppm for L1-L3 respectively;
respect are characteristic of hydrogen of imine fragment. The corresponding signals of the 13C NMR
spectra are presented at 129.0 ppm for L1, 127.3 ppm for L2 and 129.4 ppm for L3. Additionally, the
structures are supported by mass spectra, the DART mass spectra show the base peak at [M + H]+ for
molecular cation in m/z = 276 and m/z = 214 for L1 and L2 respectively, finally the mass spectra MS-
EI of L3 show molecular ions m/z = 200 for molecular ion.
3.2.
Suzuki.Miyaura cross-coupling reaction.
Initially with expected ligand L1-L3 in hand, tested the reaction of phenylboronic acid with
bromobencene in 3 mL aqueous media (Vwater/Vmethanol, 1/1) as a model reaction under 75 °C using
K3PO4 as base, L1 as ligand in the presence of Pd(OAc)2 and TBAB as additive, under IR irradiation.
We evaluate the concentration of catalytic system [Pd(OAc)2/L1], when using 1 % mol and 0.5 % mol
the reaction proceeded in excellent yields in a short time (entre 1 and 2, table 1).
As known, the base shows an important role in this reaction, various bases on the Suzuki–Miyaura
reaction were investigated (entries 2, 4-6, table 1). Among the bases employed, K3PO4 and K2CO3 were
found to be the best in the present protocol (entries 2 and 4, table 1). However, with K3PO4 the
coupling reaction proceeded in a reduced time in comparison with K2CO3.
If we kept the catalyst, base, and ligand L1 constant and used different solvents such as MeOH/H2O,
MeOH, EtOH, EtHO/H2O, the desired product was obtained in 70–99% yields (entries 7–10, table 1).
As was evidenced in Table 1 entry 8, the reaction afforded the biphenyl in an excellent yield after 5
min. shown the water was the best media for this catalyst system. After, we evaluated the reaction in
the absence of TBAB (entrie 11, table 1), and we observed excellent yields in 10 min.
We have also studied the influence of ligands L2 and L3 on catalytic activity and tested the ligand L2

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and L3 under the same reaction conditions as L1. The results are summarized in table 1 (entries 12 and
13, table 1). As can be observed, ligand L1 compared to L3 shows similar catalytic activity (entries 11
and 13, table 1), but when using L1 the time of reaction is minor.
Table 1. Optimization of conditions for the Suzuki-Miyaura cross-coupling reaction using the ligands
L1-L3.
Entry
Ligand
(% mol)
Source of Pd
(% mol)
Base
Solvent
Additive
Time
Yield TONj
(%)b
TOF
(h-1)k
(min)a
1
2
L1 (1)
L1 (0.5)
L1 (0.1)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.5)
L2 (0.5)
L3 (0.5)
L1 (0.5)
L1 (0.5)
L1 (0.25)
L1 (0.1)
L1 (0.25)
L1 (0.25)
-
Pd(OAc)2 (1)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(CNPh)2Cl2 (0.5)
Pd(PPh3)2Cl2 (0.5)
Pd(OAc)2 (0.25)
Pd(OAc)2 (0.1)
Pd(OAc)2 (0.25)
Pd(OAc)2 (0.25)
Pd(OAc)2 (0.25)
Pd(OAc)2 (0.25)
K3PO4
K3PO4
K3PO4
K2CO3
KOAc
KOH
MeOH/ H2Oc
MeOH/ H2Oc
MeOH/ H2Oc
MeOH/ H2Oc
MeOH/ H2Oc
MeOH/ H2Oc
MeOHd
H2Oe
TBAB
25
10
20
25
30
15
10
5
95
99
70
99
85
95
70
99
75
80
95
80
95
85
80
95
75
90
76
20
95
95
231
1237
2333
1414
340
TBAB
198
700
198
170
190
140
198
150
160
190
160
190
170
160
380
750
360
304
80
3
TBAB
4
TBAB
5
TBAB
6
TBAB
760
7
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
TBAB
875
8
TBAB
2385
937
9
EtOHf
TBAB
10
15
10
10
20
10
10
15
15
120
720
60
15
10
11
12
13
14
15
16
17
18h
19i
20
21l
EtOH/H2Og
H2Oe
TBAB
640
-
-
-
-
-
-
-
-
-
-
-
1187
1000
575
H2Oe
H2Oe
H2Oe
1062
1000
1520
3000
90
H2Oe
H2Oe
H2Oe
H2Oe
H2Oe
25
H2Oe
80
L1 (0.25)
H2Oe
380
1520
Reaction condiction: Bromobencene 2a (0.5 mmol), phenylboronic acid (3) (0.6 mmol), solvent (3 mL), Base (1 mmol), TBAB 0.5 mol. a
Based on total consumption of bromobencene determined by TLC. b Isolated yields. c T = 75 °C. d T = 65 °C, e T = 96 °C, f T = 78 °C g
T
h
i
= 82 °C. Under conventional heating T = 96 °C. Under room temperature. j TON = ratio of moles of product formed to moles of
catalyst used. k TOF = TON/t (h). l Preparing separately the [Pd(AcO)2/L1] catalyst system.

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Once the best ligand (L1) and appropriate solvent and base were identified, different palladium sources
such as Pd(CNPh)2Cl2 and Pd(PPh3)2Cl2 (entries 14 and 15, table 1) were tested and 4a was achieved in
good yields; however, these yields did not exceed the efficiency of Pd(OAc)2 (entry 11, table 1).
Finally, in order to use small amounts of catalyst, we carried out the reaction using 0.25 % mol and 0.1 %
mol of system catalytic [Pd(OAc)2/L1] (entries 16 and 17, table 1) and the best yield was obtained
when 0.25 % mol were used. Thus, optimized conditions for this cross-coupling reaction involves the
use of 0.25 % mol of system catalytic [Pd(OAc)2/L1], H2O as a solvent, K3PO4 as base, in the absence
of TBAB under IR irradiation.
Furthermore, when the reaction is carried out under reflux conditions using conventional heating (entry
18, table 1), obtaining a excellent yield of the coupling product 4a in a longer time. The same reaction
was performed at room temperature and achieved 4a in 76 % yield, during 12 h (entry 19, table 1). In
absence of ligand, we obtained 20% of yield (entry 20, table 1) which indicated the essential role of
hidrazone ligand.
In an effort to understand the role of the molecular structure in the complex between the hydrazone L1
and Pd(OAc)2, we carried out different reaction conditions, observed in all cases total spend of ligand,
however, it was not possible to isolate the reaction product in neither case. In our experience, believe
that hydrazone behaves as [N,N] ligand, as in other structurally similar hydrazone ligands we have
detected[34].
Additionally, we tried to formed the complex between hydrazone L1 and Pd(OAc)2 (entry 21, table 1)
before added the substrates and base, then the reaction mixture was refluxed under IR irradiation and
obtained 95 % yield. Similar yield when the reaction was made in one pot (entry 16, table 1).
With a reliable set of conditions in hand (entry 16, table 1) the scope and generality of the developed
protocol with respect to various aryl bromides and phenylboronic acids were investigated using our
catalytic system [Pd(OAc)2/L1]. When phenylboronic acid was coupled with several aryl bromides
containing both electron-donating and electron-withdrawing groups, the corresponding products were
obtained in excellent yields (entries 1-8, table 2). Due to the steric hindrance of 4-bromotoluene, 2-
bromotoluene and 2-bromo-1,3-dimethylbencene, the desired products were obtained in god yield
(entries 3-5, table 2). Similarly, when the bromobencene was coupled with several phenyl boronic acids
containing both electron-donating and electron-withdrawing groups, the reaction proceeds in excellent
yields and similar reaction time (entries 9-11, table 2) in comparison with the aryl bromides.

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We also investigated the reaction of heteroaryl bromides and aryl chlorides. The reaction the Suzuki–
Miyaura cross-coupling reaction of heteroaryl halides such as 2-bromopyridine, 3-bromopyridine, 2-
bromothiophene and 3-bromothiophene with phenylboronic acid gave the corresponding coupled
products in a good yield, (entries 12-15, table 2) but we observed the coupling reaction required
extended reaction time. Unfortunately, the coupling of 4-nitrochlorobenzene with phenylboronic acid
did not perform as well as aryl bromides, even we when raised the Pd loading up to 0.1 mol % and
prolonged the reaction time to 10 h (scheme 2) with 15 % yield.
Table 2. Scope of Suzuki-Miyaura cross-coupling of aryl bromides and phenyl boronic acids under IR
irradiation.
Entry
Ar
R’
Compound
Time
(min)a
15
Yield
(%)b
95
TONc
TOF
(h-1)d
1520
2475
848
1
2
Ph
4-CH3Ph
3-CH3Ph
2-CH3Ph
1,3-dimethylPh
4-OCH3Ph
4-ClPh
H
H
4a
4b
4c
4d
4e
4f
380
396
280
360
280
396
380
396
380
340
396
280
288
300
260
10
99
3
H
20
70
4
H
30
90
720
5
H
50
70
337
6
H
15
99
1584
2375
1584
1520
1360
1584
424
7
H
4g
4h
4f
10
95
8
4-NO2Ph
Ph
H
15
99
9
OCH3
Cl
CF3
H
15
95
10
11
12
13
14
15
Ph
4g
4i
15
85
Ph
15
99
2-Pyridyl
3-Pyridyl
2-thienyl
3-thienyl
4j
40
70
H
4k
4l
40
72
436
H
60
75
300
H
4m
60
65
260
Reaction condition: Aryl halide 2 (0.5 mmol), phenylboronic acid (3) (0.6 mmol), H2O (3 mL), K3PO4 (1 mmol), [Pd(OAc)2/L1] = 0.25
% mol, T = 96 °C. a Based on total consumption of aryl halide determined by TLC. b Isolated yields after extraction with hexane and SiO2
column chromatography. c TON = ratio of moles of product formed to moles of catalyst used. d TOF = TON/t (h).

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Scheme 2. Suzuki-Miyaura reaction using 4-nitrochlorobenzene.
In order to observe the recycling capacity of the catalytic system [Pd(OAc)2/L1], we conduct the
coupling between bromobenzene and phenylboronic acid under the optimal reaction conditions (Table
3). A flask was charged with bromobenzene, phenylboronic acid, catalytic system [Pd(OAc)2/L1],
K3PO4, and water. The mixture in open air was irradiated under IR for the 15 min.. After the mixture
was cooled, the aqueous layer was extracted with n-Hexane (3 x 5 mL), and the flask was charged
again with bromobenzene and phenylboronic acid and K3PO4. Every time after cooling and extraction
with n-Hexane, the reagents and base were added and the reaction was repeated. The recovered catalyst
was successfully reused in the subsequent three cycles, the coupled product was obtained in good
yields (entries 1-3 table 3). Nevertheless, the coupled product was significantly dropped in fourth and
fifth cycles (entries 4 and 5). Finally, a drastic decrease was observed in the six run (entries 6, table 3)
probably due to decomposition of catalyst system [Pd(OAc)2/L1].
Table 3. Recycling of catalyst.
Cycle
Yiels (%)a
TONb
380
360
320
240
180
68
TOF (h-1)c
1520
1440
1280
960
1
2
3
4
5
6
95
90
80
60
45
15
720
240
Reaction condition: Aryl halide 2 (0.5 mmol), phenylboronic acid (3) (0.6 mmol), H2O (3 mL), K3PO4 (1 mmol),
[Pd(OAc)2/L1] = 0.25 % mol, T = 96 °C. t = 15 min. a Isolated yields. b TON = ratio of moles of product formed
to moles of catalyst used. c TOF = TON/t (h).
Finally, we made a comparison of the activity of various Pd catalysts in water [Pd(OAc)2/LI] catalytic
system in the Suzuki-Miyaura coupling reaction and found that this catalyst system is advantageous in
terms of lower reaction times (entries 1-6, table 4), low catalyst loading (entries 1,3,4 and 6, table 4)

ACCEPTED MANUSCRIPT
and the absence of additives (entries 2-4, table 4).
Table 4. Catalytic performance of different catalysts in the Suzuki-Miyaura cros-coupling reaction.
Entry
Catalyst (% mol)
Β-cyclodextrin-Pd(II) complex (3%)
[NHC-Pd(II) complex] (0.2)
Conditions
K2CO3, H2O, rt.
Time
50 min
6 h
Yield
75
Ref
1
2
[24b]
[25e]
K3PO4 3H2O, H2O, TBAB,
40 °C
90
3
4
Ligand free-Pd(OAc)2 (5%)
Ligand free-PdCl2 (2 %)
Stilbazo (5 mol%), K2CO3,
H2O, rt
4 h
7h
92
98
[25d]
[28]
Na2SO4 (8 mol%), K2CO3, i-
PrOH or H2O, rt
5
6
7
N-Heterocyclic Carbene–Pd (II) (0.1)
L-arginine/PdCl2 (100/1)
Cs2CO3, H2O, 80 °C.
H2O/EtOH, r.t.
24 h
1 h
99
96
99
[29b]
[30a]
[Imidazole-hydrazone/ Pd(OAc)2] (0.25)
H2O, K3PO4, 96 °C
15 min
This work
4. Conclusions
In conclusion, we have developed a series of efficient ligands imidazole-hydrazone L1-L3, which was
easy to prepare from inexpensive and commercially available starting materials. The catalytic system
derived from these ligands and Pd(OAc)2 is an efficient catalytic system for Suzuki-Miyaura cross
coupling reaction, which can be employed in mild conditions for the coupling reaction of aryl and
heteroaryl halides. A wide range of substrates could be coupled with phenylboronic acid to afford the
desired products in good to excellent yields at low catalyst loadings and low time of reaction. Overall,
the present protocol offers a mild, efficient and attractive alternative to the existing methods because of
the use of non-toxic solvent, inorganic base and broad substrate scope.
5. Acknowledgements
The authors thank DGAPA-PAPIIT IN215116 and FES Cuautitlán-UNAM PIAPI1802 projects.
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An efficient and simple imidazole-hydrazone ligand for palladium-catalyzed Suzuki-Miyaura
cross-coupling reactions in water under infrared irradiation
Martín Camacho-Espinoza,a José Guillermo Penieres-Carrillo,a Hulme Rios Guerra,a Selene Lagunas-
Rivera,b Fernando Ortega-Jiménez.a*
Highlights
Efficient catalytic system [imidazole-hydrazone (L1-L3)/Pd(OAc)2] has been developed
The system catalyzed Suzuki-Miyaura reaction in water under IR irradiation
The system tolerates a wide range of arylboronic acids and aryl halides
The products were obtained in good yields at low catalyst loadings and low time.