Palladium-catalyzed direct C-H arylation of 2-hydroxybenzaldehydes with organic halides in neat water

Article abstract of DOI:10.1016/j.molcata.2014.10.013

The palladium-catalyzed cross-coupling of 2-hydroxybenzaldehydes with organic halides proceeds in the presence of n-Bu₄NBr in H₂O producing the corresponding 2-hydroxybenzophenones in high yields.

Full text of DOI:10.1016/j.molcata.2014.10.013

Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Palladium-catalyzed direct C H arylation of 2-hydroxybenzaldehydes
with organic halides in neat water
Najmeh Nowrouzia,∗, Somayeh Motevallib, Dariush Tarokha
a Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
b Department of Chemistry, Shiraz University, Shiraz 71454, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 June 2014
Received in revised form 5 October 2014
Accepted 10 October 2014
Available online 23 October 2014
The palladium-catalyzed cross-coupling of 2-hydroxybenzaldehydes with organic halides proceeds in
the presence of n-Bu4NBr in H2O producing the corresponding 2-hydroxybenzophenones in high yields.
© 2014 Elsevier B.V. All rights reserved.
Keywords:
Palladium
C
H arylation
2-Hydroxybenzaldehyde
Aryl ketones
Cross-coupling reaction
1. Introduction
C C bond formation has been considered as an atom economy and
an environment-friendly approach to build complex molecules in
organic chemistry [8].
Diaryl ketones have received much attention because of their
importance in pharmaceutical industries [1], natural products [2]
and also in the construction of organic molecules. Therefore, many
synthetic methods for the formation of aryl aryl, alkyl aryl, and
alkyl alkyl ketones have been developed. The classical method for
the synthesis of these compounds is based on the Friedel–Crafts
acylation in the presence of Lewis acids. Recently, catalytic systems
have been reported for the synthesis of ketones by transition-metal
catalyzed coupling reactions of carboxylic acid derivatives with
various transmetalating reagents [3]. For example, the formation of
ketones through rhodium-catalyzed C O bond activation of unac-
tivated esters using a range of organoborons has been reported
by Tian et al. [4]. Also, organometallic acyl compounds like the
other kinds of transmetalating reagents, including acylstannanes,
-silanes, and -zirconocenes with organic halides offer the synthe-
sis of ketones [5]. Carbonylative coupling of aryl halides, triflates,
and aryldiazonium salts with an organometallic species of borane,
silane, and tin in the presence of gaseous carbon monoxide [6]
or metal carbonyls as a source of carbon monoxide [7] is another
method that is commonly used for building ketone molecules. Tran-
sition metal-catalyzed aromatic C H bond functionalization for the
Among arene C H bonds, the selective activation of aldehyde
C
H bonds and coupling with aryl halides, and alkenes forming C C
bonds has been recognized as a major area of interest for access
to the array of ketone derivatives through oxidative addition of
transition-metal complexes to aldehyde C H bonds.
As an example, rhodium-catalyzed activation of aldehydes lead-
ing to the addition of the aldehyde C H bond to alkenes has
been a useful route to ketones [9]. Another approach to access
ketones from aldehydes would consist of Rh-catalyzed Heck-type
reaction of potassium trifluoro(organo)borates with aldehydes,
which was reported as the first catalytic cross-coupling reac-
tion of organometallic reagents with aryl aldehydes to afford
diaryl ketones [10]. The first palladium-catalyzed reaction of 2-
hydroxybenzaldehyde and its derivatives with aryl halides via
cleavage of the aldehyde C H bond to obtain the corresponding
ketones has been reported by Miura [11]. However, this interest-
ing protocol considerably suffers from the limitation of applying
to only aryl iodides. After this report, effort has been made for
the preparation of 2-aroylphenols using iodonium salts as ana-
logues of aryl halides. These salts were used into the reaction
with salicylaldehyde in the presence of PdCl2 and LiCl as a co-
catalyst to achieve corresponding ketones [12]. Generally, reports
on the C H arylation of 2-hydroxybenzaldehyde are very rare in
the literature. Herein, we report catalytic cross-coupling reaction of
∗
Corresponding author. Tel.: +98 771 4222341; fax: +98 771 4541494.
E-mail address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
http://dx.doi.org/10.1016/j.molcata.2014.10.013
1381-1169/© 2014 Elsevier B.V. All rights reserved.

N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
225
2-hydroxybenzaldehydes with aryl iodides and bromides to afford
2.1.5. (5-Bromo-2-hydroxyphenyl)(phenyl)methanone (Table 2,
entry 5) [55082–33–2]
diaryl ketones in water as a green solvent; while DMF was applied
as a solvent in both previous reports [11,12]. This reaction type is
of interest due to the use of water as a solvent, thus minimizing the
cost, the operational hazards, and environmental pollution.
1H NMR (250 MHz, CDCl3) ı (ppm): 11.77 (s, 1H, OH), 7.49 (d, 1H,
J = 8.5 Hz, Ar), 7.24 (m, 1H, Ar), 7.07 (d, 1H, J = 8.4 Hz, Ar), 6.97 (m,
2H, Ar), 6.85 (s, 1H, Ar), 6.56 (m, 2H, Ar). 13C NMR (62.9 MHz, CDCl3)
ı (ppm): 200.05, 158.11, 147.94, 140.55, 133.85, 133.46, 132.95,
131.25, 127.96, 127.58, 119.46.
2. Experimental
IR spectra were recorded on a Shimadzu FTIR-8300 spectrome-
ter. The 1H and 13C NMR spectra were recorded on a Brucker Avance
DPX-250 MHz spectrometer using tetramethylsilane as internal
standard.
2.1.6. (5-Bromo-2-hydroxyphenyl)(p-tolyl)methanone (Table 2,
entry 6) [215380–62–4]
1H NMR (250 MHz, CDCl3) ı (ppm): 11.63 (s, 1H, OH), 7.99 (m,
2H, Ar), 7.89 (m, 1H, Ar), 7.83 (m, 2H, Ar), 7.62 (s, 1H, Ar), 7.52 (m, 1H,
Ar), 2.76 (s, 3H, CH3). 13C NMR (62.9 MHz, CDCl3) ı (ppm): 200.93,
160.88, 149.20, 141.59 (overlap, two peaks), 136.29, 132.26, 126.47,
124.16 (overlap, two peaks), 118.85, 29.16.
2.1. General procedure for the preparation of
2-hydroxyarylketones from the reaction of
2-hydroxybenzaldehydes with aryl halides
2.1.7. 2-Hydroxybenzophenone (Table 2, entry 7) [117–99–7]
1H NMR (250 MHz, CDCl3) ı (ppm): 11.98 (s, 1H, OH), 7.56–7.48
(m, 7H, Ar), 6.96–6.92 (m, 1H, Ar), 6.77–6.71 (m, 1H, Ar). 13C NMR
(62.9 MHz, CDCl3) ı (ppm): 197.03, 139.70, 137.26, 134.33, 129.67,
129.20, 119.61 (overlap, two peaks), 119.29 (overlap, two peaks).
In a 50 mL round bottom flask equipped with a magnetic stir-
ring bar, tetrabutylammonium bromide (0.5 mmol, 0.16 g) was
added and heated at 100 ◦C to be melted. Then a mixture of PdCl2
(3 mol%, 0.0053 g), aqueous NaOH (2.0 mmol, 0.08 g of NaOH dis-
solved in 2 mL H2O), hydroxybenzaldehyde (1.0 mmol), and aryl
halide (2.0 mmol) were added to molten tetrabutylammonium bro-
mide. The progress of the reaction was monitored by TLC. After the
appropriate reaction time, the mixture was cooled to room temper-
ature and extracted with diethyl ether (3 × 5 mL). The organic layer
was isolated and dried over anhydrous Na2SO4 and purified by col-
umn chromatography over silica gel using n-hexane/ethyl acetate
as eluent to afford the highly pure desired products (Table 2).
2.1.8. 4-(2-Hydroxybenzoyl)benzonitrile (Table 2, entry 8)
[131117–91–4]
IR (KBr): 3500, 2200, 1650 cm−1 1H NMR (250 MHz, CDCl3) ı
.
(ppm): 12.00 (s, 1H, OH), 8.23–7.80 (m, 1H, Ar), 7.68–7.62 (m, 3H,
Ar), 7.59–7.52 (m, 4H, Ar). 13C NMR (62.9 MHz, CDCl3) ı (ppm):
202.85, 138.83, 132.77, 132.61 (overlap, two peaks), 124.99, 124.04
(overlap, two peaks), 119.37, 116.69 (overlap, two peaks), 116.09.
Anal. Calcd for C14H9NO2: C, 75.33; H, 4.06; N, 6.27. Found: C, 75.24;
H, 4.10; N, 6.18.
2.1.1. 2-Hydroxybenzophenone (Table 2, entry 1) [117–99–7]
IR (KBr): 3500, 1728 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
11.96 (s, 1H, OH), 7.62–7.40 (m, 7H, Ar), 7.02–6.98 (m, 1H, Ar),
6.83–6.77 (m, 2H, Ar). 13C NMR (62.9 MHz, CDCl3) ı (ppm): 200.01,
158.02, 140.77, 133.85, 133.76, 132.95, 132.04, 127.96, 127.46,
120.01 (overlap, two peaks). Anal. Calcd for C13H10O2: C, 78.77;
H, 5.09. Found: C, 78.37; H, 4.96.
2.1.9. (2-Hydroxyphenyl)(4-nitrophenyl)methanone (Table 2,
entry 9) [68223–20–1]
1H NMR (250 MHz, CDCl3) ı (ppm): 11.78 (s, 1H, OH), 8.35–8.17
(m, 3H, Ar), 7.73–7.67 (m, 3H, Ar), 7.49–7.25 (m, 2H, Ar). 13C NMR
(62.9 MHz, CDCl3) ı (ppm): 204.77, 136.88, 132.97, 132.62, 129.99,
129.97, 124.99, 123.84 (overlap, two peaks), 118.76, 118.10.
2.1.2. (2-Hydroxyphenyl)(p-tolyl)methanone (Table 2, entry 2)
[19434–30–1]
IR (KBr): 3434, 1650 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
2.1.10. (2-Hydroxyphenyl)-naphthalen-1-yl-methanone (Table 2,
entry 10) [93327–63–0]
11.97 (s, 1H, OH), 7.52–7.37 (m, 4H, Ar), 7.21 (d, 2H, J = 8.0 Hz, Ar),
6.97 (t, 1H, J = 8.5 Hz, Ar), 6.80–6.74 (m, 1H, Ar), 2.35 (s, 3H, CH3).
13C NMR (62.9 MHz, CDCl3) ı (ppm): 201.31, 163.11, 142.73, 136.07
(overlap, two peaks), 133.51, 129.46 (overlap, two peaks), 129.00,
118.53, 118.33, 30.18. Anal. Calcd for C14H12O2: C, 79.22; H, 5.70.
Found: C, 78.98; H, 5.83.
IR (KBr): 3500, 1628 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
12.21 (s, 1H, OH), 7.94–7.83 (m, 3H, Ar), 7.46–7.17 (m, 7H, Ar),
7.04–6.67 (m, 1H, Ar). 13C NMR (62.9 MHz, CDCl3) ı (ppm): 192.79,
153.44, 135.86 (overlap, two peaks), 133.00, 131.69, 131.49, 130.75,
128.95, 128.61, 128.21, 127.03, 126.21, 125.96, 123.04 (overlap, two
peaks), 119.50. Anal. Calcd for C17H12O2: C, 82.24; H, 4.87. Found:
C, 82.02; H, 4.61.
2.1.3. (2-Hydroxyphenyl)(4-nitrophenyl)methanone (Table 2,
entry 3) [68223–20–1]
IR (KBr): 3400, 1659 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
2.1.11. (2-Hydroxyphenyl)(p-tolyl)methanone (Table 2, entry 11)
[19434–30–1]
11.76 (s, 1H, OH), 8.34–7.83 (m, 6H, Ar), 7.71–7.65 (m, 2H, Ar). 13
C
1H NMR (250 MHz, CDCl3) ı (ppm): 11.88 (s, 1H, OH), 7.54–7.37
(m, 4H, Ar), 7.10 (d, 2H, J = 8.0 Hz, Ar), 6.96 (t, 1H, J = 7.8 Hz, Ar),
6.88–6.84 (m, 1H, Ar), 2.44 (s, 3H, CH3). 13C NMR (62.9 MHz, CDCl3) ı
(ppm): 201.72, 163.10, 142.83, 136.07 (overlap, two peaks), 133.51,
129.46, 129.00 (overlap, two peaks), 119.03, 119.02, 30.27.
NMR (62.9 MHz, CDCl3) ı (ppm): 137.34, 133.03, 132.61 (overlap,
two peaks), 129.97, 129.87, 124.99, 123.63, 119.13, 118.83. Anal.
Calcd for C13H9NO4: C, 64.20; H, 3.73; N, 5.76. Found: C, 64.00; H,
3.82; N, 5.70.
2.1.4. (2-Hydroxyphenyl)(o-tolyl)methanone (Table 2, entry 4)
[51974–19–7]
2.1.12. (2-Hydroxyphenyl)(p-tolyl)methanone (Table 2, entry 12)
[19434–30–1]
IR (KBr): 3400, 1670 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
11.82 (s, 1H, OH), 7.54–7.10 (m, 5H, Ar), 6.98–6.70 (m, 3H, Ar), 2.36
(s, 3H, CH3). 13C NMR (62.9 MHz, CDCl3) ı (ppm): 202.56, 157.09,
150.93, 145.57, 145.11, 130.02, 129.94 (overlap, two peaks), 125.29,
122.66 (overlap, two peaks), 119.08, 119.03, 28.17. Anal. Calcd for
1H NMR (250 MHz, CDCl3) ı (ppm): 11.87 (s, 1H, OH), 7.55–7.42
(m, 4H, Ar), 7.11 (d, 2H, J = 8.0 Hz, Ar), 6.92 (t, 1H, J = 7.9 Hz, Ar),
6.87–6.84 (m, 1H, Ar), 2.45 (s, 3H, CH3). 13C NMR (62.9 MHz, CDCl3) ı
(ppm): 201.32, 163.11, 142.73, 136.07 (overlap, two peaks), 133.51,
129.46, 129.00 (overlap, two peaks), 119.03, 119.02, 30.18.
C14H12O2: C, 79.22; H, 5.70. Found: C, 79.09; H, 5.63.

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N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
Table 1
Effect of different reaction parameters on the reaction of iodobenzene and salicylaldehydea.
O
PdCl
2
CHO
I
n-Bu NBr
Base, 100 C
4
+
o
OH
OH
Entry
Ph-I (mmol)
2.0
Base (2.0 mmol)
Time (min)
Product
Yield (%)b
96
1
2
3
4
NaOH
NaOH
Na2CO3
Bu3N
90
1.0
1.0
1.0
1.0
30
30
30
30
93
93
95
96
5c
NaOH
O
6d
1.0
2.0
2.0
NaOH
NaOH
NaOH
24 h
35
40
97
95
OH
O
7d
OH
O
8d,e
45
OH
O
9d,f
2.0
2.0
NaOH
NaOH
24 h
45
60
93
OH
10g
a
b
c
d
e
f
Reaction conditions: salicylaldehyde (1.0 mmol), base (2.0 mmol), n-Bu4NBr (0.5 mmol), PdCl2 (5 mol%) in 2 mL H2O under reflux.
Isolated yield.
LiCl (0.2 mmol) as a co-catalyst was added to the reaction mixture.
H2O (2 mL) was selected as a solvent.
The amount of PdCl2 is 3 mol%.
The amount of PdCl2 is 1 mol%.
The reaction was carried out in toluene as a solvent.
g
2.1.13. (5-Bromo-2-hydroxyphenyl)(phenyl)methanone (Table 2,
entry 13) [55082–33–2]
147.81, 144.05, 134.36, 133.26, 133.00, 132.89, 129.96, 127.77,
121.38.
1H NMR (250 MHz, CDCl3) ı (ppm): 11.80 (s, 1H, OH), 7.45 (d, 1H,
J = 8.4 Hz, Ar), 7.19 (m, 1H, Ar), 7.06 (d, 1H, J = 8.4 Hz, Ar), 6.90 (m,
2H, Ar), 6.79 (s, 1H, Ar), 6.63 (m, 2H, Ar). 13C NMR (62.9 MHz, CDCl3)
ı (ppm): 200.00, 158.02, 147.77, 140.86, 133.85, 133.46, 132.95,
132.04, 127.96, 127.58, 120.01.
2.1.15. 1-(2-Hydroxyphenyl)-2-phenyl ethanone (Table 2, entry
15) [2491–31–8]
IR (KBr): 3433, 1633 cm−1 1H NMR (250 MHz, CDCl3) ı (ppm):
.
10.40 (s, 1H, OH), 7.71–7.67 (m, 1H, Ar), 7.25–7.19 (m, 6H,
Ar), 6.86 (d, 2H, J = 8.5 Hz, Ar), 4.97 (s, 2H, CH2). 13C NMR
(62.9 MHz, CDCl3) ı (ppm): 189.60, 161.06, 135.98, 128.74, 128.37,
128.27, 127.32, 125.50, 121.00 (overlap, two peaks), 113.10, 70.39.
Anal. Calcd for C14H12O2: C, 79.22; H, 5.70. Found: C, 78.90;
H, 5.63.
2.1.14. (5-Bromo-2-hydroxyphenyl)(4-nitrophenyl)methanone
(Table 2, entry 14)
1H NMR (250 MHz, CDCl3) ı (ppm): 11.95 (s, 1H, OH), 8.16 (m,
1H, Ar), 7.98 (m, 2H, Ar), 7.89 (d, 1H, J = 8.4 Hz, Ar), 7.83 (m, 2H, Ar),
7.63 (s, 1H, Ar). 13C NMR (62.9 MHz, CDCl3) ı (ppm): 205.65, 159.12,

N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
227
Table 2
Cross coupling of salicylaldehyde with organic helidesa.
O
PdCl2 (3 mol%)
X
Z
CHO
OH
Z
n-Bu4NBr (0.5 mmol)
+
NaOH (2.0 mmol)
H2O (2 mL)
reflux
OH
R
R
Z= H, Br
X= I, Br, CH2Br
R= H, CH3, NO2, CN
Entry
Aldehyde
ArX
Time (h)
45 min
Product
Yieldb (%)ref
O
CHO
OH
I
1
2
95 [12]
90[12]
OH
O
I
I
CHO
OH
4
2
H3C
O2N
OH
O
CH3
NO2
CHO
OH
3
95[13]
OH
O
CH3
CH3
I
CHO
OH
4
5
6
13
88[13]
89[14]
85[15]
OH
O
Br
Br
CHO
OH
I
Br
Br
40 min
OH
O
CHO
OH
I
3.5
H3C
OH
CH3
O
CHO
OH
Br
7
8
6
81[12]
60[13]
OH
O
CHO
OH
Br
Br
20
NC
CN
OH
O
CHO
OH
9
18
19
75[13]
74[11]
O2N
OH
O
NO2
Br
CHO
OH
10
OH

228
N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
Table 2 (Continued)
O
PdCl2 (3 mol%)
X
Z
CHO
OH
Z
n-Bu4NBr (0.5 mmol)
+
NaOH (2.0 mmol)
H2O (2 mL)
reflux
OH
R
R
Z= H, Br
X= I, Br, CH2Br
R= H, CH3, NO2, CN
Entry
Aldehyde
ArX
Time (h)
48
Product
Yieldb (%)ref
55[12]
O
Br
CHO
OH
11
12c
13
14
H3C
OH
O
CH3
CH3
Br
CHO
OH
22
85[12]
85[14]
72[12]
H3C
OH
O
Br
Br
CHO
OH
Br
Br
Br
6
OH
O
CHO
OH
Br
16.5
O2N
OH
NO2
O
CHO
OH
Br
15d
2:20
70[13]
76[16]
OH
O
Br
CHO
OH
Br
Br
16d
2
OH
CHO
Cl
17
18
19
20
24
24
–
Trace
OH
NC
N
CHO
Cl
–
–
–
–
OH
CHO
I
I
HO
CHO
20
24
–
–
OCH3
a
Reaction conditions: organic halide (2.0 mmol), salicylaldehyde (1.0 mmol), n-Bu4NBr (0.5 mmol), PdCl2 (3 mol%), NaOH (2.0 mmol), H2O (2 mL), reflux.
Isolated yield.
PPh3 (0.12 mmol) was added to the reaction mixture.
15% Of ether product was detected.
b
c
d

N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
229
1.5
1
(A)
(B)
1.5
1
0.5
0
0.5
0 300
450
600
750
200
350
500
650
Wavelength
Wavelength (nm)
(nm)
Fig. 1. UV spectra of the palladium catalyst: (A) PdCl2, (B) n-Bu4NBr + PdCl2.
2.1.16. 1-(5-Bromo-2-hydroxyphenyl)-2-phenyl ethanone
(Table 2, entry 16) [54981–34–9]
only takes place for a short time when two molecules are in each
other vicinity. Shortly after, the molecules separate and the interac-
tion do no longer exist. As a result, the phenolic function is available
to perform the reaction with other molecules in water.
1H NMR (250 MHz, CDCl3) ı (ppm): 11.06 (s, 1H, OH), 7.30–7.27
(m, 2H, Ar), 7.15 (d, 1H, J = 8.0 Hz, Ar), 7.11 (s, 1H, Ar), 7.08–6.87
(m, 4H, Ar), 4.96 (s, 2H, CH2). 13C NMR (62.9 MHz, CDCl3) ı (ppm):
200.01, 160.69, 146.91, 137.06, 134.45, 132.07, 129.76, 123.06,
121.95, 118.16 (overlap, two peaks), 67.80.
We then applied our optimized reaction conditions (2.0 mmol
aryl halide, 5.3 mg (3 mol%) PdCl2, 1.0 mmol hydroxybenzalde-
hyde, 2.0 mmol NaOH, and 0.5 mmol n-Bu4NBr in 2.0 mL H2O
under reflux), for the reaction of different aryl halides with sali-
cylaldehydes and the desired products were obtained in good to
excellent yields (Table 2). The cross-coupling proceeded smoothly
for iodobenzene and salicylaldehyde within 45 min in excellent
yield (Table 2, entry 1). The reaction of iodobenzenes bearing
either an electron withdrawing or an electron donating group
at the para position with salicylaldehyde were carried out effi-
ciently (Table 2, entries 2 and 3). A substituent such as methyl
on the ortho position has some steric effect and slightly decreases
the yield of 2-hydroxy-2ꢀ-methylbenzophenone with elongation
of reaction time (Table 2, entry 4). Then, the applicability of this
reaction was extended to aryl bromides which makes this protocol
very attractive. Bromobenzene reacted with salicylaldehyde after
6 h, and 2-hydroxybenzophenone was obtained in excellent yield
(Table 2, entry 7). The coupling of salicylaldehyde with 4-cyano and
4-nitro substituted bromobenzene proceeded successfully (Table 2,
entries 8 and 9). Also, 1-bromonaphthalene, a more sterically hin-
dered substrate, afforded a good yield of the corresponding coupled
product (Table 2, entry 10). 4-Bromotoluene as a deactivated aryl
bromide produced a moderate yield of the corresponding ketone
after a long time (Table 2, entry 11). We decided to add PPh3
as a ligand to the reaction mixture of 4-bromotoluene and 2-
hydroxybenzaldehyde in order to decrease the reaction time and
increase the yield of product. It was observed that both yield and
reaction time were improved in the presence of PPh3 (Table 2, entry
12). The cross-coupling was also applicable to benzyl bromide, and
the corresponding product was obtained in 70% yield (Table 2, entry
15). Apart from salicylaldehyde, we extended the reaction to 5-
bromo-2-hydroxybenzaldehyde; the reaction could be carried out
with aryl iodides and bromides smoothly to give excellent yields of
the desired products under optimized reaction conditions (Table 2,
entries 5, 6, 13, 14 and 16). The reaction of 4-chlorobenzonitrile
and 4-(chloromethyl)pyridine with salicylaldehyde failed (Table 2,
entry 17 and 18). Finally, we replaced 2-hydroxybenzaldehyde
with 4-hydroxybenzaldehyde and 2-methoxybanzaldehyde, but
the starting materials remained intact (Table 2, entries 19 and
20).
3. Results and discussion
Initially, we selected the reaction of salicylaldehyede with
iodobenzene as a model reaction and studied the effects of dif-
ferent parameters on the progress of reaction (Table 1). When a
mixture of salicylaldehyde (1.0 mmol) and iodobenzene (2.0 mmol)
was heated in the presence of 5 mol% of PdCl2 and NaOH (2.0 mmol)
in n-Bu4NBr (0.5 mmol) at 100 ◦C, the only obtained product was
biphenyl and salicylaldehyde remained intact (Table 1, entry 1).
Decreasing the amount of iodobenzene from two equimolar to one,
the desired ketone was not observed (Table 1, entry 2). The use of
the other bases such as Na2CO3 as an inorganic base and n-Bu3N as
an organic base also resulted in the formation of biphenyl (Table 1,
entries 3 and 4). According to the literature [12], LiCl as a co-catalyst
with PdCl2 forms the complex Li4PdCl6, which is more reactive and
efficient. Therefore, we decided to add this co-catalyst to the reac-
tion mixture, but the reaction failed to give ketone (Table 1, entry 5).
The reaction was then conducted in water as a solvent. Surprisingly,
the most crucial component for the success of the reaction was
found to be water; a synergic effect was observed in water which
produced 2-hydroxybenzophenone under the initial condition with
100% conversion of salicylaldehyde to product (Table 1, entry 7).
The amount of iodobenzene is very effective in these reactions. By
decreasing the amount of iodobenzene, lower yield of the ketone
product and longer reaction time was observed (Table 1, entry 6).
Next, the reaction was carried out with different amounts of PdCl2
(5, 3, 1 mol%). As was shown in entries 7–9 of Table 1, 3 mol% of the
catalyst was sufficient to catalyze the reaction efficiently at 100 ◦C;
in this case; the corresponding product was obtained in 95% yield
within 45 min (Table 1, entry 8). When the cross-coupling reaction
was performed in toluene as an organic solvent, the only product
was biphenyl (Table 1, entry 10). According to the obtained results
in water, the probable reason refers to intra- and inter-H-bonding of
2-hydroxybenzaldehyde. The intramolecular hydrogen bonds are
present in the case of 2-hydroxybenzaldehyde in toluene. In this
case, the interactions within individual molecules are greater, and
there is less attraction between molecules. This causes less reactiv-
ity because the molecules are not really attracted to each other
much. On the other hand, intramolecular interactions are much
stronger since the two atoms forming the hydrogen bond remain
in each other proximity due to structure of the molecule. H2O
molecules are able to form intermolecular H-bonding with phe-
nolic function of 2-hydroxybenzaldehyde. This type of H-bonding
An important role of tetrabuthylammonium bromide was stud-
ied by UV–Vis spectra which showed conversion of Pd(II) to Pd(0)
in the presence of tetrabuthylammonium bromide by the disap-
pearance of the peaks related to Pd(II) at 450 nm (Fig. 1) [17].
Tetraalkylammonium salt additives have previously been reported
by Jeffery [18], for biphasic (organic solvent/water) Heck reactions.
It was believed that the salts were acting as phase-transfer catalysts

230
N. Nowrouzi et al. / Journal of Molecular Catalysis A: Chemical 396 (2015) 224–230
benzyl bromide with 2-hydroxybenzaldehydes in H2O to access
2-aroylketones without the need for any co-catalyst and ligand.
ArX
O
Ar
OH
O
Pd(0)
Acknowledgment
H
ArPdX
We thank the Persian Gulf University Research Council for gen-
erous partial financial support of this study.
OH
Appendix A. Supplementary data
HX
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.molcata.
2014.10.013.
O
A
B
PdHAr
O
O
H
II
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