A palladium-bisoxazoline supported catalyst for selective synthesis of aryl esters and aryl amides: Via carbonylative coupling reactions

Article abstract of DOI:10.1039/c6ra15506e

The catalytic synthesis of aryl esters and amides has been successfully achieved in the presence of the efficient palladium-bisoxazoline supported on Merrifield's resin (Pd-BOX-M). The palladium heterogeneous catalyst was prepared and characterized using various spectroscopic techniques. A bisoxazoline ligand having a suitable functional group (BOX-OH) was first synthesized, characterized, chemically supported on Merrifield's resin, and finally coordinated to palladium(ii) chloride. The catalytic activity and the recycling ability of the new palladium supported catalyst have been investigated in the alkoxycarbonylation and aminocarbonylation of various aryl iodides using different alkyl and aromatic alcohols and amines as nucleophiles. The palladium heterogeneous catalyst demonstrated excellent catalytic activity and very high recycling ability in the above two carbonylation reactions. The palladium heterogeneous catalysts showed an excellent stability under carbon monoxide and under the experimental conditions.

Full text of DOI:10.1039/c6ra15506e

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Page 1 of 22
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DOI: 10.1039/C6RA15506E
Palladium-Bisoxazoline Supported Catalyst for Selective Synthesis of Aryl
Esters and Aryl Amides via Carbonylative Coupling Reactions
Mansur B. Ibrahima, Rami Suleimanb, Mohammed Fettouhia and Bassam El Alia*
a Chemistry Department, King Fahd University of Petroleum & Minerals, Dhahran 31261, Saudi
Arabia
b Center of Research Excellence in Corrosion, King Fahd University of Petroleum & Minerals,
Dhahran 31261, Saudi Arabia
Abstract
The catalytic synthesis of the aryl esters and amides has been successfully achieved in the
presence of the efficient palladium-bisoxazoline supported on Merifield’s resin (Pd-BOX-M).
The palladium heterogeneous catalyst was prepared and characterized using various
spectroscopic techniques. A bisoxazoline ligand having a suitable functional group (BOX-OH)
was first synthesized, characterized, chemically supported on Merifield’s resin, and finally
coordinated to palladium(II) chloride. The catalytic activity and the recycling ability of the new
palladium supported catalyst have been investigated in the alkoxycarbonylation and
aminocarbonylation of various aryl iodides using different alkyl and aromatic alcohol and
amines as nucleophiles. The palladium heterogeneous catalyst demonstrated excellent catalytic
activity and very high recycling ability in the above two carbonylation reactions. The palladium
heterogeneous catalysts showed an excellent stability under carbon monoxide and under the
experimental conditions.
Keywords:
Merifield’s
resin;
palladium;
bisoxazoline;
alkoxycarbonylation;
aminocarbonylation; iodobenzene; recycling.
* Corresponding author. Tel.: +966 13 860 4491; Fax: +966 13 860 4277
E-mail address: belali@kfupm.edu.sa (B. El Ali)
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1. INTRODUCTION
Palladium catalyzed carbonylation reactions of aryl halides (carbonylative coupling) in the
presence of alcohol or amine nucleophiles represent major industrial processes for the
production of value-added bulk and fine chemicals. It is a versatile synthetic pathway which
allows the obtaining of a wide range of linear, branched and cyclic carboxylic acids and their
derivatives in one step and from easily accessible starting precursors.1-8 The products of
alkoxycarbonylation and aminocarbonylation reactions are extensively used as building blocks
for various materials ranging from polymers,9 light sensitive and electrically conductive
materials, detergents, flavors, fragrances and various pharmaceuticals.10,11
A plethora of homogeneous palladium catalysts have been described to successfully catalyze
the carbonylative coupling reactions with high selectivity, activity and low catalyst loading.12-
15
However, the complete removal of the homogeneous catalyst from the cross coupling
products is a tedious and costly process. This reduces the chances of industrial implementation
of most homogeneous palladium catalysts since metal contamination in the final products is
highly regulated by the industries.16
A suitable method for overcoming the separation problem is by immobilizing the homogeneous
catalyst on a solid support.17 Other than easy removal from the coupling products, the
immobilized catalyst can be also effectively recycled and re-used.18 The ability to separate and
reuse the supported catalyst makes it more viable alternative especially from economical point
of view. Taking into consideration the substantial advantages of supported catalysts over the
homogeneous catalysts, the interest towards the immobilization of palladium catalysts has been
increasing rapidly. Several supported palladium catalysts have been reported in literature for
the alkoxycarbonylation and aminocarbonylation of aryl iodides, where palladium particles or
complexes have been immobilized on organic polymers,19,20 functionalized silica,21,22 ZIF-8,23
MOF-5,24 porous organic polymer,25,26 and Pd/C.27-30 However, despite of their potential utility,
key obstacles for practical applications of these heterogeneous catalysts include the use of
expensive and moisture-sensitive phosphine ligands and non-recyclable metal precursors with
low catalytic activity, harsh reaction conditions and short-term stability. Hence, it is necessary
to develop highly active and stable heterogeneous catalysts for potential industrial applications.
To the best of authors’ knowledge, the application of supported palladium-bis(oxazolines)
catalysts in carbonylative coupling reactions has not been explored.
2

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As a continuation of our interest in exploring the chemistry and catalytic activities of
palladium-bisoxazoline catalysts,31-33 we wish to report in this study, the synthesis and
characterization of a palladium-bisoxazoline complex supported on Merifield’s resin (Pd-
BOX-M). The catalytic activity and recycling ability of the new supported catalyst in
alkoxycarbonylation and aminocarbonylation reactions of aryl iodides have been studied.
2. EXPERIMENTAL
2.1. Materials
Materials for the synthesis of ligands and complexes were purchased from Sigma - Aldrich
Company and were used as received. All solvents (reagent grade) used in the synthesis were
distilled and dried before use. Merifield’s peptide resin (50 – 100 mesh, extent of labelling:
2.5-4.0 mmol/g Cl- loading, 1% crosslinked with divinylbenzene) was also purchased from
Sigma-Aldrich. The products were purified using flash column chromatography packed with
Silica gel 170-400 Mesh, Fisher chemical (Fisher scientific, US). Merck 60 F254 silica gel plates
(250 µm layer thickness) were used for thin-layer chromatography (TLC) analyses.
2.2. Instrumentation
1H and 13C NMR spectral data were obtained using 500 MHz NMR machine (Joel 1500 model).
Chemical shifts were recorded in ppm using tetramethyl silane (TMS) as a reference and CDCl3
was used as NMR solvent. Solid state NMR spectral data was recorded using CP-MAS on a
Bruker Avans 400 MHz machine. IR spectra were recorded in wave numbers (cm-1) using FT-
IR spectrometer (Perkin-Elmer 16F model). A Varian Saturn 2000 GC-MS machine equipped
with a 30 m capillary column was used to analyze the products. Agilent 6890 Gas
chromatograph (GC) was used to monitor the reactions and analyze the products. Elemental
analyses were performed on Perkin Elmer Series 11 (CHNS/O) Analyzer 2400. Palladium
loading was estimated using inductively coupled plasma- mass spectrometer, X-series 2 ICP-
MS, thermos scientific. X-ray photoelectron spectroscopy (XPS) (Thermo Scientific,
ESCALAB-250Xi) was employed to find the chemical composition of the supported
palladium-bisoxazoline catalysts. The XPS spectra were recorded using Al K radiation (1486.6
eV) as excitation source. The take-off angle θ of the emitted photoelectrons was adjusted to
45° with respect to the normal surface.
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2.3. Synthesis of bisoxazoline ligand (BOX-I)
The BOX ligand was prepared using an earlier published procedure.31-33 A solution of 4-
iodophthalonitrile (4.0 mmol) and zinc triflate (5.0 mol%, 0.2 mmol) in dried chlorobenzene
(30 mL) was stirred at room temperature for 15 minutes. A solution of 2-Amino-2-methyl-1-
propanol (8.0 mmol) in dry chlorobenzene (5 mL) was slowly added. The temperature was
raised to 135 oC and the reaction mixture was refluxed for 24 hours. The solvent was removed
using rotary evaporator. The crude product was dissolved in 30 mL of dichloromethane and
extracted twice with distilled water (2 x 20.0 mL). The aqueous layer was then separated and
the combined organic layers were dried with anhydrous sodium sulfate. The dichloromethane
was removed using a rotary evaporator to obtain the impure product, which was then purified
using silica gel column chromatography with dichloromethane/ether (4/1) as eluent.
2,2'-(4-Iodobenzene-1,2-diyl)bis(4,4-dimethyl-4,5-dihydro-1,3-oxazole) (BOX-I)
Yield 94 %; waxy solid; 1H NMR (500 MHz, CDCl3) δ (ppm): 8.01 (s, 1H, C-3 arom), 7.73 (d,
J =10 Hz, 1H, C-5 arom), 7.38 (d, J = 10 Hz, 1H, C-6 arom), 3.99 (s, 2H,OCH2), 3.98 (s, 2H,
OCH2), 1.30 (s, 6H, CH3 x 2); 1.29 (s, 6H, CH3 x 2); 13C NMR (125 MHz, CDCl3) δ (ppm);
27.95 (CH3 x 4), 67.92 (NCH x 2), 79.40 (OCH2 x 2), 96.12 (C-4 arom), 127.89 (C-1 arom),
130.11 (C-2 arom), 130.97 (C-6 arom), 138.26 (C-5 arom), 139.07 (C-3 arom), 160.82 (C-4’),
161.47 (C-1’); IR (KBr) υ (cm-1) 2963, 2884, 1642, 1458, 1398, 1352, 1303, 1194, 1089, 1039,
964, 824, 723; GC-MS m/z 398 (M+); Anal. Calc. for C16H19IN2O2 (398.24): C, 48.26; H, 4.81;
N, 7.03. Found: C, 48.44; H, 4.88; N, 7.22.
2.4. Synthesis of hydroxyl functionalized bisoxazoline ligand (BOX-OH)
2,2'-(4-Iodobenzene-1,2-diyl)bis(4,4-dimethyl-4,5-dihydro-1,3-oxazole)
(BOX-I)
(0.50
mmol), PdCl2 (0.025 mmol, 5.0 mol%), K2CO3 (1.0 mmol, 2.0 mol equivalent), DMF (2 mL),
distilled water (2 mL) and the 4-hydroxy phenylboronic acid (0.6 mmol), were added in a 10
o
mL round bottom flask. The mixture was stirred at 70 C for 6h. After completion of the
reaction, the mixture was cooled down and acidified with 1M HCl. The acidified solution was
extracted 3 times with EtOAc and the combined EtOAc extract was dried using anhydrous
MgSO4. The solvent was removed under reduced pressure and the product was purified by
silica gel column chromatography using hexane-EtOAc (1:9) as an eluent.
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3,4'-Bis(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)biphenyl-4-ol (BOX-OH)
Yield 94 %; Light brown oil; 1H NMR (500 MHz, CDCl3) δ (ppm): 7.81 (s, 1H), 7.79 (d, J =
10 Hz, 1H), 7.57 (d, J = 10 Hz, 1H), 7.25 (s, 2H), 6.82 (d, J = 10 Hz, 2H), 4.18 (s, 2H, OCH2),
4.14 (s, 2H, OCH2),1.51 (s, 6H, NC(CH3)2), 1.44 (s, 6H, NC(CH3)2); 13C NMR (125 MHz,
CDCl3) δ (ppm); 28.0 (NC(CH3)2), 28.1 (NC(CH3)2), 67.7 (NC(CH3)2), 67.9 (NC(CH3)2), 79.6
(OCH2), 79.9 (OCH2), 116.1, 116.2, 125.7, 127.9, 128.2, 130.3, 130.4, 143.4, 157.3, 162.5,
164.1; IR (CH2Cl2) υ (cm-1) 3189, 2968, 2929, 2893, 1650, 1605, 1522, 1460, 1358, 1276,
1177, 1098, 964, 829. GC-MS m/z 364 (M+); Anal. Calc. for C22H24N2O3 (364.44): C, 72.51;
H, 6.64; N, 7.69. Found: C, 72.25; H, 6.38; I; N, 7.52.
2.5. Synthesis of supported bisoxazoline ligand on Merifield’s resin (BOX-M)
NaH (0.50 mmol) was added in one portion to a stirred solution of 3,4'-bis(4,4-dimethyl-4,5-
dihydro-1,3-oxazol-2-yl)biphenyl-4-ol (BOX-2) (0.30 mmol) in dry DMF in a dry flask. The
mixture was stirred for 2h at room temperature and under argon atmosphere. Merifield’s resin
o
(0.30 mmol) was added and the mixture was stirred at 90 C for 12h. The solid product was
filtered and washed successively with methanol, water, acetone and dichloromethane. The
product was dried at room temperature under vacuum.18
Supported bisoxazoline ligand on Merifield’s resin (BOX-M)
Yellow solid; 91% yield; CP-MAS NMR: δ 28.2, 41.7, 67.9, 80.3, 91.4, 120-140 (several
signals), 168.8; IR: vmax (cm-1) 3081, 3024, 2965, 2923, 1652, 1604, 1517, 1491, 1452, 1351,
1311, 1244, 1086, 1036, 825, 759, 699.
2.6. Synthesis of palladium(II)-bisoxazoline supported on Merifield’s resin
(Pd-BOX-M)
The Merrifield’s resin supported bisoxazoline ligand (BOX-3) (0.30 mmol) was stirred in
anhydrous ethanol for 30 min. An ethanolic solution of bis(benzonitrile) palladium(II) chloride
(0.30 mmol) was added and the resulting mixture was stirred at 50 oC for 12h. The solid product
was filtered, washed thoroughly with ethanol and dried in vacuum.34
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Palladium-Bisoxazoline supported on Merifield’s resin (Pd-BOX-M)
Dark brown solid, 95% yield; CP-MAS NMR: δ 27.5, 41.4, 70.5, 81.7, 96.1, 120-140 (several
signals), 182.3; IR: vmax (cm-1) 3056, 3021, 2919, 2844, 1634, 1599, 1494, 1452, 1371, 1327,
1221, 1178, 1068, 1011, 950, 824, 757, 699.
Metal loading from ICP-MS: 6.7% corresponding to 0.6 mmol/g.
2.7. General procedure for the alkoxycarbonylation of aryl iodides
A basic stainless steel autoclave equipped with a glass liner, gas inlet valve and pressure gauge
was used for the reaction. (Pd-BOX-M) catalyst (0.0050 mmol based on palladium),
iodobenzene (1.0 mmol), KOH (2.0 mmol) and alcohol (5.0 mL) were added in the glass liner
which was then placed in 45 mL autoclave. The autoclave was vented three times with CO and
o
then pressurized to 100 psi CO. The mixture was heated to 100 C and maintained at this
temperature under stirring for the required time. After the reaction is complete, the mixture was
cooled down to room temperature and the excess of CO was released under fume hood. The
catalyst was carefully separated from the product. The product mixture was immediately
analyzed with GC and GC-MS. The recovered catalyst was carefully washed and dried under
vacuum in a desiccator before the next use.
2.8. General procedure for the aminocarbonylation of aryl iodides
A basic stainless steel autoclave equipped with a glass liner, gas inlet valve and pressure gauge
was used for the reaction. (Pd-BOX-M) catalyst (0.0050 mmol based on palladium),
iodobenzene (1.0 mmol), amine (2.0 mmol), triethylamine (3.0 mmol), and acetonitrile (5.0
mL) were added to the glass liner. The glass liner was then placed in 45 mL autoclave. The
autoclave was vented three times with CO and then pressurized to 100 psi CO. The mixture
was heated to 120 oC and maintained at this temperature under stirring for the required time.
After the reaction is complete, the mixture was cooled down to room temperature and the
excess of CO was released under fume hood. The catalyst was carefully separated from the
product. The product mixture was immediately analyzed with GC and GC-MS. The recovered
catalyst was carefully washed and dried under vacuum in a desiccator before the next use.
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3. RESULTS AND DISCUSSION
3.1. Synthesis and characterization of the palladium-bis(oxazoline) supported on
Merrifield’s resin (Pd-BOX-M)
The iodo functionalized ligand (BOX-I) was prepared from the reaction of 4-iodophthalonitrile
with 2 mol equivalent of 2-amino-2-methyl-1-propanol. The hydroxyl functionalized ligand
(BOX-OH) was prepared from the Suzuki-Miyaura cross coupling reaction of BOX-1 with 4-
hydroxyphenylboronic acid (Scheme 1).
The Merrifield’s resin was functionalized with the bis(oxazoline) ligand (BOX-OH) to form
Merrifield’s resin supported BOX ligand (BOX-M) followed by a subsequent complexation
with palladium chloride to form the polymer supported palladium-bis(oxazoline) catalyst (Pd-
BOX-M) (Scheme 2). The BOX ligands were characterized using analytical and spectroscopic
techniques including 1H and 13C NMR, FT-IR, GC-MS, and elemental analysis. The formation
of the Pd-BOX-M catalyst was confirmed by FT-IR, CP-MAS NMR, ICP-MS. SEM, XPS and
TGA techniques.
I
I
Zn(Otf)
HO
NH
2
2
+
2
C6H5-Cl, 140 oC
O
O
N
N
CN
CN
BOX-I
2
B(OH)
[Pd], K CO
2
3
HO
OH
O
1. NaH, DMF
RT, 2 h
O
O
N
N
O
O
N
N
.
2
Cl
90 oC, 12 h
BOX-OH
BOX-M
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Scheme 1: Synthesis of Merrifield’s supported BOX ligand (BOX-M)
O
O
Ethanol
+
PdCl (PhCN)
2 2
50 oC, 12h
O
O
O
O
N
N
N
N
Pd
Cl Cl
BOX-M
Pd-BOX-M
Scheme 2: Synthesis of supported Pd-BOX-M catalyst
The formation of resin supported bis(oxazoline) ligand was confirmed by the appearance of a
strong band at 1652 cm-1 in the free ligand and at 1634 cm-1 due to the its complexation with
palladium. This peak was initially absent in the spectrum of the unmodified Merrifield’s resin.
This band is due to the stretching of imino (-C=N-) bond of the oxazoline ring. The shift in the
position of the imino band (∆ν = 18 cm-1) confirms the coordination of palladium with the
supported ligand.
The Merrifield’ resin supported BOX-M ligand and its palladium catalyst (Pd-BOX-M) were
further analyzed using solid state 13C NMR. The NMR data of the polymer bound ligand and
its palladium catalyst showed that the resonance due to imino carbon (-C=N) was observed at
168.8 in the spectrum of the supported ligand. This band shifted to 182.3 after complexation.
The palladium loading on the polymer supported palladium catalyst which was analyzed using
ICP-MS, was estimated as 6.7% (0.6 mmol/g). The thermal stability of both the resin supported
ligand and its palladium catalyst was established from the TGA analyses. The Merrifield’s resin
supported BOX ligand and its palladium catalyst where found to possess high thermal stability
with decomposition temperature greater than 350 oC.
XPS analysis was carried out on the supported catalyst in order to get insight on the nature of
the palladium atom in the complex. The XPS spectrum of the fresh supported catalyst showed
several peaks for palladium in the range of 335 to 341 eV. Two distinctive 3d peaks were
8

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identified. The first peak is with binding energy of 334.98 eV (Pd3d5/2) and the second peak is
with binding energy of 340.28 (Pd3d3/2). These peaks correspond to palladium(II) forms, which
confirm that palladium(II) is the main form of palladium in the supported catalyst.
3.2. Evaluation of the catalytic activity of Pd-BOX-M catalyst in the
alkoxycarbonylation of aryl iodides
Palladium-catalyzed alkoxycarbonylation reaction of aryl halides is a versatile reaction for the
synthesis of various aromatic carboxylic acids and their derivatives. The reaction is of synthetic
value due to the exceptionally low cost of carbon monoxide and from the diversity of aromatic
esters that can be achieved by selecting the proper alcohol. In our investigation, we have chosen
the methoxycarbonylation of iodobenzene using Pd-BOX-M catalyst as a model reaction. We
have studied the influence of various reaction parameters including temperature, base, solvent,
and the type of palladium catalyst.
A preliminary alkoxycarbonylation reaction of iodobenzene (1a) with methanol (2a) using the
o
catalytic system ([Pd-BOX-M] / KOH / CH3OH / 70 C) (Table 1, entry 1) yielded 50% of
methyl benzoate (3aa) after 3 h reaction. The catalytic activity was found to be highly
temperature dependent. The yield of 3aa increased significantly from 50% to 85% when the
temperature was raised from 70 oC (Table 1, entry 1) to 100 oC (Table 1, entry 2) and to 90%
yield at 110 oC (Table 1, entry 3). Full conversion of iodobenzene and almost quantitative yield
of the ester was obtained on raising the temperature to 120 oC (Table 1, entry 4). The selectivity
was not affected by changing the reaction temperature.
We have further screened various at 120 oC. Potassium hydroxide gave excellent yield (99%)
of the product 3aa (Table 1, entry 4). Similarly, full conversion and almost quantitative yield
was obtained with NaOH (Table 1, entry 5). Potassium carbonate gave 96% of the methyl
benzoate (Table 1, entry 6). The use of an organic base such as triethylamine resulted in an
excellent yield of the required ester (93%) (Table 1, entry 7). We have then studied the
optimized reaction using acetonitrile as a solvent and methanol as a nucleophile (Table 1, entry
8), where comparable excellent yield of the ester was achieved.
The effect of the type of palladium catalyst on the methoxycarbonylation of iodobenzene was
investigated. No product was obtained in the absence of palladium catalyst (Table 1, entry 9).
Pd-BOX-M (Table 1, entry 4) yielded a full conversion and 100% selectivity in favor of the
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methyl benzoate. We have further compared the catalytic activity of our newly prepared Pd-
BOX-M with some commercially available palladium complexes and salts such as
Pd(PPh3)2Cl2 (Table 1, entry 10) (96%), Pd(PhCN)2Cl2 (Table 1, entry 11) (99%), Pd(OAc)2
(Table 1, entry 12) (95%) and Pd/C (Table 1, entry 13) (84%). Interestingly, the activity of the
palladium salts and complexes reported in this study and the supported complexes reported in
19-30
literature
were similar in activity to our Pd-BOX-M catalyst. However, Pd-BOX-M has
the potential to be recycled and reused for large number of runs for the same or similar
reactions, and consequently possessing high turnover number (TON) and turnover frequency
(TOF) values.
Table 1. Palladium-Bisoxazoline supported on Merifield’s resin (Pd-BOX-M)
catalyzed methoxycarbonylation of iodobenzene (1a).a
O
I
[Pd], Base
100 psi, T (oC)
OCH3
+ CH3OH + CO
1a
2a
3aa
T
Yield
3aa
Solvent
(5 mL)
Entry
Pd-Complex
Base
(oC)
(%)b
1
2
Pd-BOX
Pd-BOX
Pd-BOX
Pd-BOX
Pd-BOX
Pd-BOX
Pd-BOX
Pd-BOX
-
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
CH3CN/CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
Neat CH3OH
KOH
KOH
KOH
KOH
NaOH
K2CO3
Et3N
70
50
85
100
110
120
120
120
120
120
120
120
120
120
120
3
90
4
99
5
99
6
96
7
93
8
KOH
KOH
KOH
KOH
KOH
KOH
99
9
Traces
96
10
11
12
13
Pd(PPh3)2Cl2
Pd(PhCN)2Cl2
Pd(OAc)2
Pd/C
99
95
84
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a. Reaction conditions: [Pd] (0.0050 mmol), iodobenzene (1.0 mmol), solvent (5.0 mL),
base (2.0 mmol), CO (100 psi), 3 h.
b. GC Yield.
3.3. Methoxycarbonylation of iodobenzene catalyzed by Pd-BOX-M catalyst. Recycling
ability
The recycling ability of Pd-BOX-M supported catalyst was investigated in the
methoxycarbonylation reaction of iodobenzene at 100 psi CO pressure and a temperature of
100 oC for 6 h. The result of the recycling experiment is presented on Figure 1. Remarkably,
the supported catalyst could be recycled up to ten times devoid of substantial loss in its catalytic
activity. The TON of the supported catalyst was estimated for the 10 cycles as 1884, while the
TOF was estimated as 314/h. In order to confirm the effectiveness and the high activity realized
with the supported catalyst, we have conducted experiment with the amount of iodobenzene
equal to the total amount used in all the ten cycles (10.0 mmol) using the same quantity of
supported palladium-bisoxazoline catalyst (0.005 mmol) (substrate to catalyst ratio equals to
2000). Excellent yield of methyl benzoate (95%) was recorded. Similarly, the TON of the
supported palladium-bisoxazoline catalysts in the later experiment was estimated as 1860,
while the TOF was estimated as 310/h.
100
90
80
70
60
50
40
30
20
10
1
2
3
4
5
6
7
8
9
10
No. of Run
Figure 1. Methoxycarbonylation reaction of iodobenzene. Recycling ability of Pd-BOX-M.
Reaction conditions: [Pd-BOX-M] (0.0050 mmol), iodobenzene (1.0 mmol), methanol (5.0
mL), KOH (2.0 mmol), CO (100 psi), 100 oC, 6 h.
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3.4. Pd-BOX-M catalyzed alkoxycarbonylation of aryl iodides. Effect of various
substrates
The excellent recycling ability realized with the new supported palladium-bisoxazoline catalyst
(Pd-BOX-M) in the methoxycarbonylation of iodobenzene encouraged us to study the scope
of the supported catalyst in the alkoxycarbonylation reaction of a broad range of substrates
using a CO pressure of 100 psi and KOH as a base. Thus, the alkoxycarbonylation of
iodobenzene with various alcohols including aliphatic (primary, secondary and tertiary
aliphatic alcohols) as well as aromatic alcohols were studied (Table 2). All considered alcohols
gave excellent conversions, and in some cases the corresponding esters were isolated in
excellent yields. Primary aliphatic alcohols (Table 2, entries 1-3) reacted smoothly to yield the
corresponding aromatic esters. The reactivity of primary alcohols was not affected by the length
of the carbon chain, however, secondary and tertiary aliphatic alcohols were relatively less
reactive compared to the primary alcohols and therefore longer reaction time was required to
achieve full conversions of the alkoxycarbonylation reactions (Table 2, entries 4 and 5). In
these reactions, the alcohol served both as a nucleophile and as a solvent. The
alkoxycarbonylation reaction of iodobenzene with phenol was carried out using acetonitrile as
a solvent (Table 2, entry 7).
The impact of electronic effect of various aryl iodides on their reactivity in the carbonylation
reactions was also studied. Both activated and deactivated aryl iodides worked effectively to
lead to the corresponding aromatic esters. The presence of a deactivating group on the aryl
iodide enhanced its reactivity and the corresponding ester was isolated in excellent yield (94%)
(Table 2, entry 9). Similarly, 4-iodoanisole reacted smoothly to give methyl 4-
methoxybenzoate (Table 2, entry 10) in high yield. The methoxycarbonylation of 1,4-
diiodobenzene was also successful and yields 92% of dimethylbenzene-1,4-dicarboxylate
(Table 2, entry 11).
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Table 2. Alkoxycarbonylation of aryl iodide by the Pd-BOX-M catalyst.a
O
I
[Pd], KOH
OR'
+ R'OH + CO
100 psi, 100 oC
R
R
1
2
3
Aryl Iodide
1a-d
Alcohol
2a – h
Product (ester)
3a – k
Time
(h)
Yield
Entry
(%)b,c
O
I
CH3OH
O
1
6
6
99
2a
1a
3aa
O
I
OH
O
2
3
4
5
99
96
2b
1a
3ab
I
O
OH
O
6
2c
1a
3ac
O
I
O
12
12
95
OH
2d
1a
3ad
O
I
O
99 [92]
OH
1a
2e
2f
3ae
O
I
OH
O
6
7d
8
12
6
99 [93]
99 [95]
99 [92]
1a
3af
O
I
OH
O
2g
1a
3ag
O
I
OH
O
6
2h
1a
3ah
O
I
O
CH3O
CH3OH
O
9
6
99 [94]
2a
O
O
1b
3ba
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O
I
O
CH3OH
10
11
6
96 [90]
MeO
2a
O
O
1c
3ca
3da
O
I
O
CH3OH
12
99 [92]
I
2a
O
1d
a. Reaction conditions: [Pd-BOX-M] (0.0050 mmol), aryl iodide (1.0 mmol), alcohol (5 mL),
KOH (2.0 mmol), CO (100 psi), 100 oC
b. GC yield.
c. Isolated yields are given in brackets.
d. Phenol (2.0 mmol), CH3CN (5.0 mL), 120 oC.
3.4. Aminocarbonylation of iodobenzene with diisobutylamine catalyzed Pd-BOX-M
catalyst. Recycling Ability
Palladium-catalyzed aminocarbonylation of aryl halides is a widely used methodology in the
synthesis of carboxamides from easily accessible starting materials. Various amides including
those with bulky N-substitutions can easily be produced by selecting the suitable aryl halide
and amine. We have tested the catalytic activity of our palladium supported catalyst (Pd-BOX-
M) in the aminocarbonylation of aryl iodides. Various amines were considered in this reaction.
The recycling ability of Pd-BOX-M was also investigated in the aminocarbonylation reaction
of iodobenzene with diisobutylamine (DIBA) in the presence of trimethylamine as a base at
o
100 psi CO pressure and a temperature of 120 C for 6 h. The results of the recycling
experiments are presented on Table 3. The supported catalyst was recycled up to six times with
no significant loss in its catalytic activity. However, a drop in the conversion of iodobenzene
to 61 % was observed with the supported catalyst during the seventh cycle, which reflects some
deactivation of the catalyst due to the leaching of palladium in the presence of trimethylamine
and amine as a nucleophile, .ꢀ02'!*#ꢁꢀ%%0#%ꢀ2'-,ꢁ-0ꢁ.-'1-,',%.
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Table 3. Aminocarbonylation of iodobenzene with diisobutylamine (DIBA).
Recycling ability of Pd-BOX-M catalyst.a
O
O
N
I
[Pd]
N
+
+ CO + HN
O
Et3N, CH3CN
100 psi, 120 oC
1a
4a
5aa
6aa
Product Distributionc
%
Conversionb
Cycle
%
5aa
96
95
96
96
96
96
95
6aa
4
1
2
3
4
5
6
7
99
99
99
92
88
85
61
5
4
4
4
4
5
a . Reaction conditions: [Pd-BOX-M] (0.0050 mmol), iodobenzene (1.0 mmol),
(2.0 mmol), Et3N (3.0 mmol), acetonitrile (5.0 mL), CO (200 psi), 120 oC, 6 h.
b. Determined by GC based on iodobenzene.
DIBA
c. Determined by GC.
3.5. Aminocarbonylation of various aryl iodides catalyzed by Pd-BOX-M catalyst
We have extended the scope of the aminocarbonylation reaction to different amines including
primary and secondary amines as nucleophiles and various aryl iodides (Table 4, entries 1-7)
as substrates. The aminocarbonylation reaction was found to be highly dependent on the type
of the amine employed. For instance, secondary amines such as diisobutylamine (4a) and
dicyclohexylamine (4b) reacted smoothly with iodobenzene (1a) (Table 4, entries 1 and 2,
respectively). The reaction of iodobenzene with diisobutylamine yielded the corresponding
carboxamide (5aa) in 96% selectivity and 4% of ketocarboxamide (6aa). However, the reaction
of iodobenzene with dicyclohexylamine yielded the carboxamide (6ab) as the only product.
The aminocarbonylation of iodobenzene with aniline (4c) as nucleophile was also successful
and yielded N-phenylbenzamide (6ac) selectively as the sole product (Table 4, entry 3). The
supported catalyst Pd-BOX-M also gives excellent conversions in the aminocarbonylation of
iodobenzene with primary amines as nucleophiles (Table 4, entry 4). However, in contrast to
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secondary amines, primary amines show relatively poor selectivity and a mixture of mono
carbonylation and double carbonylation products were obtained (Table 4, entries 4 and 5).
The effect of the type of the substituent on the aryl iodide was also investigated in our
aminocarbonylation reaction (Table 4). Interestingly, Pd-BOX-M was highly active in the
aminocarbonylation reactions of both activated and deactivated aryl iodides. For instance, the
aminocarbonylation of 4-iodoanisole (1b) and methyl 4-iodobenzoate (1c) with
diisobutylamine were achieved to give excellent conversions and very high selectivities toward
the production of the corresponding expected carboxamides (Table 4, entries 6 and 7).
The aminocarbonylation of 1,4-diiodobenzene (1d) with dicyclohexylamine (4b) was also
successful and yields 99% of diamide as the only product of the reaction (Table 4, entry 8).
Table 4. Aminocarbonylation of aryl iodides using Pd-BOX supported on Merifield’s
Resin as Catalyst.
O
O
I
NR1R2
[Pd]
+
NR1R2
+ CO +
R1R2NH
O
Et3N, CH3CN
100 psi, 120 oC
R
R
R
1
4
5
6
Product
Aryl halide
1 a-d
Conversionb
%
Entry
Amine
4a–e
Distributionc
%
5
6
I
NH
96
5aa
4
6aa
1
2
99
99
1a
4a
I
N
H
100
5ab
0
0
1a
4b
I
NH2
100
5ac
3
4
99
99
4c
1a
NH2
I
65
5ad
35
6ad
4d
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1a
1a
1b
I
NH2
70
5ae
30
6ae
5
6
99
99
4e
I
NH
96
5ba
4
6ba
MeO
4a
I
NH
CH3O
93
5ca
7
6ca
7
8
99
99
O
1c
4a
I
N
H
100
5db
0
I
1d
4b
a. Reaction conditions: Pd-BOX-M (0.0050 mmol), Aryliodide (1.0 mmol), amine (2.0 mmol),
Et3N (3.0 mmol), CO (100 psi), 120 oC, 6 h.
b. Percent conversion determined by GC based on aryl iodide.
c. Determined by GC.
3.6. Characterization of the recycled Pd-BOX-M catalyst
The ability to reuse the supported palladium-bisoxazoline complex several times and in various
reactions without significant loss in their catalytic activities demonstrates their interesting
stabilities. The interesting results realized with the supported catalysts urged us to carry out
further investigations to asses any change in the physical and chemical structures of the used
catalysts in comparison with the unused complexes. The recovered catalysts from all the two
applications were analyzed with Fourier Transform Infrared Spectroscopy (FT-IR), X-Ray
Photoelectron Spectroscopy (XPS) and Inductively Coupled Plasma – Mass Spectrometry
(ICP-MS) techniques.
The recovered palladium-bisoxazoline catalyst was washed successively with distilled water,
acetone and methanol. The catalyst was then dried in an oven at 100 oC prior to analysis. The
dried catalyst was pressed into disc with KBr and analyzed using FT-IR. The FT-IR spectrum
for the recovered merifield’s resin supported palladium-bisoxazoline catalysts (Figure 2a) was
found to be similar with the spectrum of the unused catalyst (Figure 2b).
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(a)
(b)
Figure 2. FT-IR spectra of the supported Pd-BOX catalyst: (a) fresh catalyst and (b)
recovered catalyst from the alkoxycarbonylation reaction
The percentage of palladium on the supported catalyst recovered after the tenth cycle of the
alkoxycarbonylation reaction were determined using ICP-MS and were found to be 6.0%.
Whereas, the amount of palladium on the supported catalyst recovered after the seventh cycle
of the aminocarbonylation reaction was estimated as 5.1%.
These results indicate that the amount of palladium on the supported catalyst recovered from
alkoxycarbonylation reactions are similar to the amount of palladium in the unused catalyst
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and could be the reason for the promising recycling ability observed in the alkoxycarbonylation
reaction.
On the other hand, the amount of palladium on the supported catalyst recovered from
aminocarbonylation reaction was much less than the amount of palladium on the unused
supported complex (there is a 24 % loss of palladium). This could be the reasons for the
decrease in the catalytic activity observed in the later cycles of the aminocarbonylation
experiments.
The XPS spectra of the supported palladium-bisoxazoline recovered after the tenth cycle of the
alkoxycarbonylation reaction (Figure 3a) show that the oxidation state of palladium remains
unchanged after the catalytic application (Figure 3b). Similar to the unused supported catalyst,
the 3d spectrum resolved into 3d5/2 and 3d3/2 spin orbit pairs with binding energies of 334.88
eV and 339.98 eV, respectively.34, 35
Pd3d Scan
Pd3d Scan
1.50E+05
1.00E+05
5.00E+04
0.00E+00
1.50E+05
1.00E+05
5.00E+04
0.00E+00
350
340
330
350 345 340 335 330
Binding Energy (eV)
Binding Energy (eV)
(a)
(b)
Figure 3. XPS Spectrum of Pd-BOX-12 Recovered from Alkoxycarbonylation reaction
showing the Pd 3d, (right spectrum) Spectrum of fresh catalyst is displayed on the left
3.7. Study of the palladium leaching from the support during carbonylation reactions
The main objective of supporting a homogeneous catalyst is to enable its easy separation from
the product and to minimize the level of contamination caused by the toxic metal. The possible
palladium leaching into the product was analyzed using ICP-MS. After the tenth cycle of the
alkoxycarbonylation and the seventh cycle of the aminocarbonylation, the products of each
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reaction were combined in separate containers. Samples were taken from each reaction for the
analysis. The samples were digested using concentrated nitric acid. The solutions were then
analyzed with ICP-MS technique.
The results of the ICP-MS analysis show that the concentration of palladium in the
alkoxycarbonylation product is 2.0 ppb. This means that less than 0.1 % of the total palladium
on the supported complex was leached into the solution. On the other hand, the amount of
palladium that leached into the solution during the aminocarbonylation reaction was 195.0 ppb.
This amount was estimated as 3.4 % of the total palladium on the supported catalyst. These
results clearly show that the palladium leaching during aminocarbonylation reaction was
significantly higher than the alkoxycarbonylation reaction, which explains the reason for the
relatively lower recycling ability encountered during the aminocarbonylation reaction as
compared to the alkoxycarbonylation reaction. The higher leaching of palladium observed with
the aminocarbonylation reaction could be attributed to the coordination of palladium to the
amine (either trimethylamine base or the amine nucleophile). This results in the formation of
homogeneous complexes that are highly soluble in the liquid phase.36
4. CONCLUSIONS
In summary, we reported successfully the application of an innovative palladium-bisoxazoline
complex supported on Merifield’s resin as a highly active heterogeneous catalyst in the
production of aryl esters and amides via alkoxycarbonylation and aminocarbonylation of
various aryl iodides. The palladium heterogeneous catalysts showed an excellent stability and
recycling ability. The process represents a simple and attractive method for the production of
highly value-added esters and amides that should be of high interest to many chemical and
petrochemicals companies.
5. ACKNOWLEDGEMENTS
This project was funded by the National Plan for Science, Technology and Innovation
(MARIFAH) - King Abdulaziz City for Science and Technology - through the Science &
Technology Unit at King Fahd University of Petroleum & Minerals (KFUPM), the Kingdom
of Saudi Arabia, award number (14-PET2737-04).
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