Synthesis and palladium(II) metal chemistry of thiazoline/imidazoline derived ligands: An efficient catalyst for cross-coupling reactions of arylboronic acids with acid chlorides and aryl halides

Article abstract of DOI:10.1016/j.ica.2018.09.012

The synthesis, reactivity, spectroscopic characterization and catalytic activities of a series of Pd(II) complexes bearing the chelating ligands 2-(4,5-dihydrothiazol-2-yl)aniline (2) and 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (3) are reported. The reactions of 2 with [Pd(COD)Cl₂] in 1:1 and 1:2 (ligand into metal and metal into ligand) molar ratios afforded the mononuclear complexes, PdCl₂{κ²?N,S ? 2?(4,5-dihydrothiazol-2-yl)aniline} (4), Pd{κ²?N,N’?2?(4,5-dihydrothiazol-2-yl)aniline}₂ (5) and Pd{κ₁²?N,N’?κ₂²?N,S ? 2?(4,5-dihydrothiazol-2-yl)aniline}₂ (6), respectively, in good yields. The neutral mononuclear palladium complexes PdCl₂{κ²?N,N’?(4,5-dihydro-1H-imidazol-2-yl)aniline} (7) and Pd{κ²?N,N’?2?(4,5-dihydro-1H-imidazol-2-yl)aniline}₂ (8) were synthesized using [Pd(COD)Cl₂] with appropriate molar ratios. The palladium complexes 4–8 were evaluated for their catalytic activities in base assisted cross coupling reactions between acid chlorides and aryl halide with boronic acids. The complex 4 was found to be an efficient catalyst for producing unsymmetrical ketones (TOF = 19.8 min^?1) while complex 7 was effective for making biaryls (TOF = 19.8 min^?1).

Full text of DOI:10.1016/j.ica.2018.09.012

Accepted Manuscript
Research paper
Synthesis and Palladium(II) Metal Chemistry of Thiazoline/Imidazoline De-
rived Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylbor-
onic Acids with Acid Chlorides and Aryl Halides
Murugesan Sudharsan, D. Suresh
PII:
S0020-1693(18)31379-3
https://doi.org/10.1016/j.ica.2018.09.012
ICA 18470
DOI:
Reference:
Inorganica Chimica Acta
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Revised Date:
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11 August 2018
4 September 2018
Please cite this article as: M. Sudharsan, D. Suresh, Synthesis and Palladium(II) Metal Chemistry of Thiazoline/
Imidazoline Derived Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylboronic Acids with Acid
Chlorides and Aryl Halides, Inorganica Chimica Acta (2018), doi: https://doi.org/10.1016/j.ica.2018.09.012
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Synthesis and Palladium(II) Metal Chemistry of Thiazoline/Imidazoline Derived
Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylboronic Acids with
Acid Chlorides and Aryl Halides
Murugesan Sudharsan and D. Suresh*
Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed
University, Thanjavur, Tamil Nadu, 613 401, India
*Corresponding author e-mail: suresh_d@scbt.sastra.edu
1

Abstract
The synthesis, reactivity, spectroscopic characterization and catalytic activities of a series of
Pd(II) complexes bearing the chelating ligands 2-(4,5-dihydrothiazol-2-yl)aniline (2) and 2-
(4,5-dihydro-1H-imidazol-2-yl)aniline (3) are reported. The reactions of 2 with [Pd(COD)Cl2]
in 1:1 and 1:2 (ligand into metal and metal into ligand) molar ratios afforded the mononuclear
complexes, PdCl2{2N,S2(4,5-dihydrothiazol-2-yl)aniline} (4), Pd{2N,N’2(4,5-
2
2
dihydrothiazol-2-yl)aniline}2 (5) and Pd{1 N,N’2 N,S2(4,5-dihydrothiazol-2-
yl)aniline}2 (6), respectively, in good yields. The neutral mononuclear palladium complexes
PdCl2{2N,N’(4,5-dihydro-1H-imidazol-2-yl)aniline} (7) and Pd{2N,N’2(4,5-
dihydro-1H-imidazol-2-yl)aniline}2 (8) were synthesized using [Pd(COD)Cl2] with
appropriate molar ratios. The palladium complexes 4 – 8 were evaluated for their catalytic
activities in base assisted cross coupling reactions between acid chlorides and aryl halide with
boronic acids. The complex 4 was found to be an efficient catalyst for producing unsymmetrical
ketones (TOF = 19.8 min-1) while complex 7 was effective for making biaryls (TOF = 19.8
min-1).
Key words: thiazoline/imidazolyl ligands, palladium(II) chemistry, cross-coupling reactions,
unsymmetrical ketones, biaryls
2

1. Introduction
The importance of transition-metal complexes mediated homogeneous catalysis have been
emerged as active field over the years as they yield valuable products and new functional
groups by using extremely small amounts of catalysts[1]. The ability to precisely control the
structure of a catalyst through manipulation of both the metal and ligand perhaps more
important for fine tuning the catalytic performances[2]. Consequently, the catalytic activity
originates from the metal and the organic ligands control the binding of reactants and their
subsequent reaction paths through steric and electronic interactions in the catalysis. Recent
studies demonstrate that the higher catalytic activity is achieved when the coordination sphere
around the metal centers have significantly different donor groups attributed by the hemi-labile
ligands[3]. The 2-aryl substituted thiazoline/imidazoline is an important organic heterocycles,
containing N and S donor atoms in the core structures show selectivity and good chelation
depends upon reaction with metal precursors in the synthesis of metal complexes[4].
The unsymmetrical ketone frameworks are common functional group in synthetic organic
chemistry with wide applications such as pharmaceutical, fragrance and agrochemical
industries[5]. Due to their versatility and wide applicability, numerous methods and strategies
for their preparation such as oxidation of the corresponding secondary alcohol[6],
Friedel−Crafts acylation[7], and reaction of acyl chlorides with organometallic reagents[8]
have been reported. However, these reaction suffers some drawback, such as reaction
conditions, low substrate scope, stoichiometric amount of catalyst and releasing large amount
of side products. Alternative transformations used to construct these diaryl ketones involve the
transition metal mediated coupling reactions of carboxylic anhydrides[9], esters[10], thiol
esters[11] with organometallic compounds. Palladium, a transition metal, has very high
functional group tolerance and makes it an attractive metal to investigate its catalytic
applications[12]. Palladium-catalyzed cross-coupling reactions comprise one of the most
3

productive methods for the development of C−C, C−N, and C−O bonds[13]. These cross-
coupling reactions have considered as straight forward synthetic tools in numerous organic
synthesis and playing an important role in the fine-chemical industries.
The palladium catalyzed cross-coupling reaction of acid chlorides with arylboronic acids for
the production of unsymmetrical ketone is known for few years, still the catalytic system
suffers from lower turnover frequency (TOF = 0.017  0.62 min-1)[1419]. In order to realize
an environmentally benign, non-toxic, low catalyst loading, non-additives for the production
of diaryl ketones with high TOF, herein, we explore the palladium complexes containing the
thiazoline/imidazoline hemi-labile ligands to catalyze the cross-coupling reactions of acid
chlorides with arylboronic acids to access aryl ketones and aryl bromides with phenylboronic
acid to produce biaryls.
2. Experimental Section
All reagents and solvents were purchased from commercial suppliers (Sigma-Aldrich, Alfa
Aesar, and Avra Synthesis) and used without further purification. The reactions were
monitored by thin-layer chromatography using Merck silica gel 60 F254 and visualized by UV
detection. Melting points were recorded on a melting point apparatus in capillaries and are
uncorrected.
The nuclear magnetic resonance (NMR) spectra were recorded in deuterated solvents at room
temperature on a Bruker Avance 300 (1H, and 13C) spectrometer operating at 300 MHz for 1H
and 75 MHz for 13C. Deuterated solvents were dried by storage over 4Ȧ molecular sieves.
Chemical shifts (δ) are expressed in ppm using TMS as internal standard and coupling
constants (J) are given in Hz. Multiplicities were abbreviated as follows: broad (br), singlet (s),
doublet (d), triplet (t), quartet (q), heptet (h), and multiplet (m). GC analyses were performed
on Agilent 7820A GC fitted with FID detector and capillary column. FTIR spectra were
4

obtained using a Bruker Tensor 27 series FTIR spectrometer by mixing sample with KBr and
taking readings in the range of 400–4000 cm−1 were reported. Elemental analyses were
determined by Euro EA - Elemental Analyser.
2.1 Synthesis of 2-(4,5-dihydrothiazol-2-yl)aniline (2)
The 2-(4,5-dihydrothiazol-2-yl)aniline (2) was prepared by modifying the previously reported
procedure[20]. 2-aminobenzonitrile (1) (2.00 g, 16.93 mmol), cysteamine hydrochloride (2.88
g. 25.39 mmol) and NaOH (0.203 g, 5.08 mmol) were suspended in a round bottomed flask
stirred under a pre-heated oil bath at 80 C and the reaction was monitored in TLC. The
reaction mixture was cooled down to room temperature and then added with ice cold water and
then extracted with dichloromethane three times. The solvents were removed under vacuum
1
and dried to give yellow oil of 2. Yield: 96% (2.90 g, 16.27 mmol). H NMR (300 MHz,
CDCl3): δ 7.48 (d, 9.1 Hz, 1H, Ar-H), 7.32-7.11 (m, 1H, Ar-H), 6.78-6.55 (m, 2H, Ar-H), 6.20
(s, 2H, NH2), 4.50 (t, 7.5 Hz, 2H, NCH2), 3.28 (t, 7.5 Hz. 2H, SCH2).
2.2 Synthesis of 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (3)
The 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (3) was prepared by neat reaction of 1 (1.00 g,
8.46 mmol) and ethylenediamine (10.2 g, 169.2 mmol) suspended in a round bottomed flask
kept at 120 C and stirred for 6 h. The progress of the reaction was monitored through TLC.
The reaction mixture was cool down to room temperature and add with ice cold water. The
product was extracted with ethyl acetate for three times and further purified through column
chromatography (EtOAc:Hexane) to afford white solid of 3. Yield: 88 % (1.20 g, 7.44 mmol).
1H NMR (300 MHz, CDCl3) δ 7.32 (dd, 9.0, 1.2 Hz, 1H, Ar-H), 7.25-7.11 (m, 1H Ar-H), 6.70
(dd, 9.0, 1.2 Hz, 1H, Ar-H), 6.68-6.59 (m, 1H, Ar-H), 3.75 (s, 4H, -CH2). 13C NMR (75 MHz,
CDCl3) δ 165.43, 148.29, 131.12, 127.80, 116.27, 116.01, 111.65, 49.72. IR (KBr pellets,
cm−1): 3405, 3229, 2920, 2857, 1615, 1507, 1483, 1327, 1257, 1160, 987, 744.
5

2.3 Synthesis of complex PdCl2{2N,S2(4,5-dihydrothiazol-2-yl)aniline} (4)
A dichloromethane (10 mL) solution of Pd(COD)Cl2 (0.025 g, 0.0876 mmol) was added
dropwise into a well stirred solution of 2 (0.01561 g, 0.0876 mmol) in the same solvent (5 mL).
The reaction mixture was stirred at room temperature for further 3 h. During which time the
clear yellow solution turned to yellow precipitate. The formed yellow precipitate was filtered,
washed with ether and vacuum-dried to afford 4. Yield: 99 % (0.031 g, 0.0872 mmol). Melting
point: > 165 C (decomposed). 1H NMR (300 MHz, CDCl3/DMSO-D6) δ 7.70 (m, 1H, Ar-H),
7.66 – 7.56 (m, 2H, Ar-H), 7.44 – 7.39 (m, 1H, Ar-H), 7.37 (bs, 2H, -NH2), 4.51 (t, 9.0 Hz, 2H,
NCH2), 3.62 (t, 9.0 Hz, 2H, NCH2). 13C NMR (75 MHz, CDCl3/DMSO-D6) δ 170.46, 137.06,
133.24, 130.36, 127.46, 125.22, 121.32, 63.21, 31.00. IR (KBr pellets, cm−1): 3466, 3241,
3027, 1601, 1568, 1490, 1329, 1251, 1045, 763. Anal. Calcd for C9H10Cl2N2PdS: C, 30.51; H,
2.82; N, 7.91. Found C, 30.43; H, 2.89; N, 7.58.
2.4 Synthesis of Pd{2N,N’2(4,5-dihydrothiazol-2-yl)aniline}2 (5)
312 g, 0.1752 mmol)
Pd(COD)Cl2 (0.025 g, 0.0876 mmol)
he clear
yellow solution was turned to yellow precipitate. The precipitate was filtered, washed with
hexane and dried under vacuum to produce complex 5. Yield: 91 %. (0.034 g, 0.1974 mmol).
Melting point: > 180 C (decomposed). 1H NMR (300 MHz, CDCl3/DMSO-D6) δ 7.70 (d, 9.0
Hz, 1H, Ar-H), 7.64 – 7.53 (m, 2H, Ar-H), 7.41 (m, 1H, Ar-H), 7.37 (s, 2H, -NH), 7.30 (dd,
9.0, 1.6 Hz, 1H, Ar-H), 7.18-7.10 (m, 1H, Ar-H), 6.75 (d, 9.0 Hz, 1H, Ar-H), 6.58-6.51 (m,
1H, Ar-H), 4.49 (t, 9.0 Hz, 2H, NCH2), 4.42 (t, 9.0 Hz, 2H, NCH2), 3.27 (t, 7.5 Hz, 4H, SCH2).
13C NMR (75 MHz, CDCl3 / DMSO) δ 170.52, 137.10, 133.24, 130.40, 125.25, 121.30, 63.20,
31.00. IR (KBr pellets, cm−1): 3420, 3077, 2866, 1605, 1555, 1492, 1450, 1329, 1247, 1205,
6

1050, 766. Anal. Calcd for C18H18Cl2N4PdS2: C, 40.75; H, 3.39; N, 10.57. Found C, 39.72; H,
3.39; N, 10.45.
2
2
2.5 Synthesis of Pd{1 N,N’2 N,S2(4,5-dihydrothiazol-2-yl)aniline}2 (6)
A solution of 2 (0.03123 g, 0.1752 mmol) in dichloromethane (10 mL) was added dropwise
into the solution of Pd(COD)Cl2 (0.025 g, 0.0876 mmol) also in dichloromethane (10 mL) over
a period of 5 minutes. The initial clear yellow colored solution turns yellow precipitate after 10
minutes of stirring and the reaction mixture was allowed to stir at room temperature for further
2h. The yellow precipitate obtained was filtered and washed two times with hexane and dried
to yield compound 6. Yield: 94 %. (0.035 g, 0.0759 mmol). Melting point: > 195 C
(decomposed). 1H NMR (300 MHz, CDCl3/ DMSO) δ 7.71 (d, 9.0 Hz 1H, Ar-H), 7.66 – 7.56
(m, 2H, Ar-H), 7.46 – 7.39 (m, 1H, Ar-H), 7.38 (br s, 2H, -NH), 7.31 (dd, 9.0, 1.5 Hz, 1H, Ar-
H), 7.18-7.11 (m, 1H, Ar-H), 6.76 (dd, 7.5, 1.5 Hz, 1H, Ar-H), 6.59 – 6.51 (m, 1H, Ar-H), 4.50
(t, 9.0 Hz, 2H, NCH2), 4.44 (t, 9.0 Hz, 2H, NCH2), 3.62 (t, 9.0 Hz, 2H, SCH2), 3.28 (t, 7.5 Hz,
2H, SCH2). 13C NMR (75 MHz, CDCl3 / DMSO) δ 170.49, 137.14, 133.00, 130.35, 125.30,
121.26, 63.04, 31.33. IR (KBr pellets, cm−1): 3420, 3079, 2892, 1606, 1555, 1492, 1450, 1329,
1247, 1204, 1050, 766. Anal. Calcd for C18H18Cl2N4PdS2: C, 40.75; H, 3.39; N, 10.57. Found
C, 39.72; H, 4.11; N, 9.97.
2.6 Synthesis of PdCl2{2N,N’(4,5-dihydro-1H-imidazol-2-yl)aniline} (7)
Pd(COD)Cl2 (0.025 g, 0.0876 mmol) is dissolved in 10 mL of dichloromethane was added into
a dichloromethane (10 mL) solution of 3 (0.01411 g, 0.0876 mmol) at room temperature. The
resultant reaction mixture was allowed to stir for further 5 h and a yellow precipitate was
formed. The yellow precipitate was filtered, washed with ether and vacuum-dried to get the
compound 7. Yield: 91 % (0.027 g, 0.0797 mmol). Melting point: > 210 C (decomposed). 1H
NMR (300 MHz, CDCl3/DMSO) δ 9.04 (bs, 1H, NH), 8.63 (s, 1H, Ar-H), 7.73 – 7.53 (m, 2H,
7

Ar-H), 7.41-7.34 (m, 1H, Ar-H), 3.91-3.58 (m, 4H). IR (KBr pellets, cm−1): 3420, 3197, 2947,
1605, 1563, 1487, 1280, 1192, 1057, 772. Anal. Calcd: C9H11Cl2N3Pd: C, 32.05; H, 3.26; N,
12.46: Found C, 34.7: H, 3.81; N, 11.9.
2.7 Synthesis of Pd{2N,N’2(4,5-dihydro-1H-imidazol-2-yl)aniline}2 (8)
This reaction was carried out by following the synthesis of 6, by taking Pd(COD)Cl2 (0.025 g,
0.0876 mmol) and 3 (0.02823 g, 0.1751 mmol). Yield: 96 % (0.04 mg, 0.0937 mmol).1H NMR
(300 MHz, CDCl3/DMSO) δ 8.87 (bs, 2H, NH), 7.89 (d, 9.0 Hz, 2H, Ar-H), 7.76 (d, 9.0 Hz,
1H, Ar-H), 7.50-7.40 (m, 2H, Ar-H), 7.37-7.24 (m, 1H, Ar-H), 5.56 (s, 4H, N-CH2), 3.82 (s,
4H, (H)N-CH2). IR (KBr pellets, cm−1): 3444, 3196, 2948, 1605, 1563, 1486, 1284, 1202, 1059,
767. Anal. Calcd: C18H20N6Pd: C, 50.70: H, 4.69; N, 19.71: Found C, 50.38: H, 5.89; N, 19.75.
2.8 Typical procedure for the coupling reactions between acid chloride and boronic acid
The round-bottom flask was placed with the appropriate amount of catalyst, and 5 mL of
CH3CN was added to it. After stirring for 5 min, acid chloride (0.5 mmol), arylboronic acid
(0.55 mmol), and LiOH.H2O (2 mmol) were introduced into the reaction flask. The mixture
was heated at 80 C for the required time (the course of reaction was monitored by GC
analysis), following which the solvent was removed under reduced pressure. The residue was
diluted with water (8 mL) and EtOAc (8 mL) followed by extraction twice (2 – 6 mL) with
EtOAc. The combined organic fractions were dried (MgSO4), stripped of the solvent under
vacuum, and the residue was dissolved in 5 mL of dichloromethane. An aliquot was taken with
a syringe and subjected to GC analysis. Yields were calculated versus acid chlorides as an
internal standard.
2.9 Typical procedure for the coupling reactions between aryl bromides and boronic acid
The round-bottom flask was placed with the appropriate amount of catalyst, and 5 mL of
methanol was added to it. After stirring for 5 min, aryl bromide (0.5 mmol), phenylboronic
8

acid (0.55 mmol), and K2CO3 (1 mmol) were introduced into the reaction flask. The mixture
was heated at 60 C for the required time (the course of reaction was monitored by GC
analysis), following which the solvent was removed under reduced pressure. The residue was
diluted with water (8 mL) and EtOAc (8 mL) followed by extraction twice (2 – 6 mL) with
EtOAc. The combined organic fractions were dried (MgSO4), stripped of the solvent under
vacuum, and the residue was dissolved in 5 mL of dichloromethane. An aliquot was taken with
a syringe and subjected to GC analysis. Yields were calculated versus aryl bromides as an
internal standard.
2. 10 Synthesis of [1,1'-biphenyl]-4-yl(phenyl)methanone (9)
4-bromobenzoyl chloride (0.5 mmol), phenyl boronic acid (1.1 mmol), LiOHH2O (2 mmol),
0.5 mol % of catalyst 4 and CH3CN (5 mL) were introduced into the reaction flask. The mixture
was heated at 80 C for the required time (the course of reaction was monitored by GC analysis),
following which the solvent was removed under reduced pressure. The residue was diluted with
water (8 mL) and EtOAc (8 mL) followed by extraction twice (2 – 6 mL) with EtOAc. The
combined organic fractions were dried (MgSO4), stripped of the solvent under vacuum, and the
residue was dissolved in 5 mL of dichloromethane. An aliquot was taken with a syringe and
subjected to GC analysis. Yields were calculated versus 4-bromobenzoyl chloride as an internal
standard. Yield: 89 %. 1H NMR (300 MHz, CDCl3) δ 8.30-8.20 (m, 5H, Ar-H), 7.78-7.71 (m,
2H, Ar-H), 7.64-7.57 (m, 2H, Ar-H), 7.56-7.48 (m, 5H, Ar-H), 7.47-7.37 (m, 2H, Ar-H).
3. Results and Discussion
3.1 Synthesis of ligands and palladium metal complexes
The 2-aryl substituted thiazoline/imidazoline ligands, 2-(4,5-dihydrothiazol-2-yl)aniline (2)
and 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (3) were prepared by condensation of 2-
aminobenzonitrile (1) with cysteamine hydrochloride and ethylenediamine (Scheme 1) in good
9

yields. The ligands 2 and 3 are air and moisture stable which are soluble in all common organic
solvents. They are characterized by spectroscopic techniques and are consistent with the
literature value[20].
Scheme 1. Synthesis of ligands 2 and 3
The equimolar reaction by the addition of [Pd(COD)Cl2] into the dichloromethane solution of
2 produced the mono-chelated complex PdCl2{2N,S2(4,5-dihydrothiazol-2-yl)aniline} (4)
in 99% yield. A similar reaction was carried out with two equivalents of 2 and one equivalent
of [Pd(COD)Cl2] afforded the bis-chelated mononuclear complex, Pd{2N,N’2(4,5-
dihydrothiazol-2-yl)aniline}2 (5) (Scheme 2). Under the similar stoichiometric conditions (1:1
and 1:2), by reversing the addition of the reactants, adding ligand 2 into the dichloromethane
solution of [Pd(COD)Cl2], resulted in the formation of bis-chelated mononuclear complex
2
2
Pd{1 N,N’2 N,S2(4,5-dihydrothiazol-2-yl)aniline}2 (6) in good yields.
Treatment of [Pd(COD)Cl2] with one equivalent of ligand 3 in dichloromethane, afforded
corresponding mononuclear complex PdCl2{2N,N’(4,5-dihydro-1H-imidazol-2-yl)aniline}
(7) while the reactions with two equivalents of 3 produced the neutral Pd{2N,N’2(4,5-
dihydro-1H-imidazol-2-yl)aniline}2 (8) in 91 and 96% of yields, respectively (Scheme 3). All
the palladium complexes 4 – 8 were bright yellow in color and were precipitated from the
reaction mixtures which are isolated by filtration. The complexes 4 – 8, both in solution and
in solid state at room temperature, were found to be non-hygroscopic and are stable in air. The
complexes 4 – 8 were insoluble in dichloromethane, diethyl ether, tetrahydrofuran and
acetonitrile but soluble in methanol and dimethyl sulfoxide.
10

Scheme 2. Synthesis of palladium complexes 4  6
1
The palladium complexes 4 – 8 were characterized by H and 13C NMR spectroscopic
techniques. The 1H NMR spectrum of 4 show two triplet at 4.51 and 3.62 ppm corresponds to
N-CH2 and S-CH2 protons of the thiazoline moiety (Figure 1). The S-CH2 protons shows
downfield shift of 0.34 ppm compared to the free ligand 3 (S-CH2 triplet at 3.28 ppm) confirms
the coordination of sulfur to the palladium metal center. For 5, S-CH2 protons (3.27 ppm)
remains unchanged while the N-CH2 protons show two triplets at 4.49 and 4.42 ppm represent
the nitrogen coordination to the palladium center. The proton NMR spectrum of 6 shows two
sets of triplets at 4.50 and 4.44 ppm for N-CH2 protons while the S-CH2 protons appeared at
3.62 and 3.28 ppm and are consistent with the proposed structure. A multiplet around 3.91-
3.58 ppm (for N-CH2 and NH-CH2) for the palladium complex 7 was observed while the
complex 8 shows two singlets at 5.56 and 3.82 ppm respectively for the N-CH2 and NH-CH2
protons in their corresponding 1H NMR spectra which are in accordance with the structure.
Scheme 3. Synthesis of palladium complexes 7 and 8
11

Figure 1. 1H NMR spectra of 2, 4 – 6 recorded with CDCl3 (with one drop of DMSO-D6)
3.2 Cross-Coupling Reactions Catalyzed by Palladium Complexes 4 – 8
The palladium-catalyzed cross-coupling reaction is known with a variety of transmetallating
agents. In particularly, the palladium-catalyzed cross-coupling of boronic acids with acid
chloride derivatives[21] and aryl halides (Suzuki–Miyaura cross-coupling reaction)[22] have
been developed as a powerful protocol to synthesize unsymmetrical aromatic ketones and
biaryls is the most attractive and practical protocol because of its tolerance for a wide range of
functional groups.
3.2.1 Cross-coupling Reactions of Arylboronic Acids with Acid Chlorides:
To evaluate the activity of the palladium complexes 4 – 8, an initial model reaction was carried
out using phenylboronic acid (1.1 mmol) and benzoyl chloride (1.0 mmol) as reactants,
complex 4 as catalyst (0.5 mol %), K2CO3 (4 mmol) as base and toluene (5 mL) as solvent.
The model reaction resulted in the formation of 35% yield of benzophenone (Table 1, entry 1),
12

the coupled product. To further improve the yields of the product the inorganic (Na2CO3,
LiOHH2O, NaOAc, K3PO4) and organic (TEA and DABCO) bases have been screened under
similar reaction conditions (Table 1, entries 2 – 9). The results indicated that the use of
LiOHH2O as base resulted in high conversion of benzophenone (Table 1, entry 3). To further
improve the yields, the different solvents were used to perform the reactions by keeping the
base as constant and found that use of acetonitrile resulted in 100 % yields of benzophenone
(Table 1, entry 12). Performing the reaction in room temperature resulted in poor conversion
of the coupled product. Finally, the exploration of various catalyst systems (4 – 8) was carried
out and the results are summarized in table 2. The mononuclear complex 4 was found to be an
effective catalyst (Table 2, entry 1) to carry out this cross coupling reaction and also observed
that decrease in catalyst loading led to decrease in the catalytic activity (Table 2, entry 1, 6 and
7). A controlled reaction was carried out under similar reaction condition in the absence of
catalyst or base, no cross-coupling reaction occurs.
Table 1. Optimization of base and solvent for cross coupling reactions between benzoyl
chloride and phenylboronic acid.
Temperature
(°C)
Time
(min)
30
Yielda
(%)
35
Entry
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Base
K2CO3
110
1
2
3
4
5
6
7
8
Na2CO3
LiOHH2O
NaOAc
K3PO4
110
110
110
110
110
110
25
30
30
2
100
17
88
62
88
2
30
30
TEA
30
DABCO
DABCO
30
120
13

Toluene
Toluene
MeOH
CH3CN
CH3CN
H2O
LiOHH2O
No Base
110
110
80
300
300
300
10
89b
Nil
10
9
10
11
12
13
14
LiOHH2O
LiOHH2O
LiOHH2O
LiOHH2O
80
100
2
25
10
100
30
10
aReaction condition: Benzoyl chloride (1 mmol), phenylboronic acid (1.1 mmol),
Pd catalyst 4 (0.5 mol %), base (4 mmol) and solvent (5 mL). b 2 mmol of base
Table 2. Optimization of catalysts for cross coupling reactions between benzoyl chloride and
phenylboronic acid
mol
%
Time
(min)
Yield
(%)a
Entry
1
Catalyst
0.5
30
100
0.5
0.5
60
60
80
80
2
3
14

0.5
0.5
60
60
100
85
4
5
0.2
0.4
30
30
65
6
80
7
8
no catalyst
no reaction
Reaction condition: Benzoyl chloride (1 mmol), phenylboronic acid (1.1 mmol), Pd
catalyst, LiOHH2O (4 mmol) using acetonitrile (5 mL) as solvent at 80 C.
Under the optimized reaction conditions, to explore the scope of this reaction various benzoyl
chloride derivatives were allowed to react with arylboronic acids. (Table 3). The benzoyl
chlorides containing both electron withdrawing and electron releasing substituent facilitates
the coupling and furnished the desired products in good to excellent yields. The use of
terephthaloyl chloride furnished the desired bis coupled product with excellent yield as a single
product (Table 3, entries 12 and 13). In addition, the use of heteroaryl boronic acid, thiophene-
2-boronic acid, were also found to be an effective reactant in the coupling reaction with the
15

acid chloride derivatives to afford very good to excellent conversion (Table 3, entries 3, 6, 11,
14). To the best of our knowledge, the catalytic ability of catalyst 4 was excellent (TOF = 19.8
min-1), when compared to the previously reported palladium mediated coupling reaction of acid
chloride with arylboronic acids with TOF value ranging from 0.017 to 0.62 min-1 (Table 4).
Table 3. Scope of substrate for cross coupling reactions between acid chloride and arylboronic
acid under the optimized reaction conditions
Time Yielda
TOF
Entry
1
Acid chloride
Boronic acid
Product
(min)
(%)
(min-1)
10
99
19.8
9.9
20
99
2
15
10
99
99
13.2
19.8
3
4
20
99
9.9
5
16

15
10
98
99
13.07
19.8
6
7
10
20
10
10
99
98
97
99
19.8
9.8
8
9
19.4
19.8
10
11
10
10
99b
19.8
19.8
12
13
99b
17

20
99b
9.9
14
aReaction condition: Acid chloride (1 mmol), arylboronic acid (1.1 mmol), Pd catalyst 4 (0.5 mol%),
LiOHH2O (4 mmol) using acetonitrile (5 mL) as solvent at 80 C. b arylboronic acid (2.1 mmol)
Table 4. Comparison of catalytic performances of catalyst 4 with other reported catalysts for
cross coupling reactions between acid chloride and arylboronic acid
TOF
No
1
Literature
Reference
(min-1)
[14]
0.017
[15]
[16]
0.025
0.62
2
3
[17]
0.118
4
3.2.2 Cross-coupling Reactions of Arylboronic Acids with Aryl halides:
18

[18]
0.255
5
[19]
0.087
6
7
19.8
This work
To further extend the catalytic applications of the newly synthesized palladium complexes 4 –
8, the Suzuki-Miyaura cross-coupling reaction was carried out. To optimize the reaction
conditions, the palladium complex 4 was chosen as the catalyst, 4’-bromoacetophenone and
phenylboronic acid were chosen as reactants, the base, solvent and the temperature were varied
in order to obtain the high yields of biphenyl derivatives. The optimized results are shown in
the table 5. Under the optimized reaction conditions (methanol as solvent, K2CO3 as base), the
catalysts 4 – 8 were screened to the find the better catalyst to effect this cross coupling reaction
was carried out and the results are summarized in table 6. Eventually, the catalyst 7 with 0.5
mol% of loading was found to be effective coupling catalyst.
Table 5. Optimization of base and solvent for cross coupling reactions between 4’-
bromoacetophenone and phenylboronic acid.
19

Temperature
Time
(hours)
2
Yielda
(%)
99
Entry
Solvent
MeOH
Base
K2CO3
Na2CO3
Cs2CO3
TEA
(°C)
70
1
MeOH
70
70
6
6
74
55
80
25
70b
-
2
MeOH
3
MeOH
70
6
4
MeOH
DABCO
K2CO3
No base
K2CO3
K2CO3
K2CO3
K2CO3
70
6
5
MeOH
70
6
6
MeOH
70
12
6
7
H2O
100
70
60
61
93
55
8
THF
16
16
6
9
Toluene
MeOH:H2O (1:1)
120
80
10
11
aReaction condition: 4’-bromoacetophenone (1 mmol), phenylboronic acid (1.1 mmol), Pd
catalyst 4 (0.5 mol %), base (1 mmol) and solvent (5 mL). b 0.5 mmol of base.
Table 6. Optimization of catalysts for cross coupling reactions between 4’-bromoacetophenone
and phenylboronic acid
mol
%
Time
(Hour)
Yield
(%)a
Entry
1
Catalyst
0.5
0.5
1
1
92
70
2
20

0.5
0.5
0.5
1
1
1
78
99
98
3
4
5
1
-
0.5
-
99
6
7
No catalyst
No reaction
Reaction condition: 4’-bromoacetophenone (1 mmol), phenylboronic acid (1.1 mmol),
Pd catalyst, K2CO3 (1 mmol) using methanol (5 mL) as solvent at 70 C.
With the optimized reaction conditions, the scope and limitations of the current investigation
was explored using a diverse range of aryl halides bearing electron-donating and/or electron-
withdrawing substituents and the results are summarized (Table 7). The results were promising
and it was observed the presence of electron withdrawing groups in the aryl bromides enhances
the catalytic reaction (Table 7, entries 13) while the electron releasing substituent (Table 7,
entries 1112) takes relatively longer time to convert into the coupled biaryl product. The ortho
substituted aryl bromides reacts sluggishly (Table 7, entries 1314) compared to meta- and
21

para- substituted aryl bromides (Table 7, entries 810) indicating that the steric nature plays an
important role in the coupling reaction.
Table 7. Scope of substrate for cross coupling reactions between aryl bromides and
phenylboronic acid under the optimized reaction conditions
TOF
Time Yield
Entry
1
Aryl halide
Product
(min-
(min)
(%)
1
)
10
96
19.2
6.6
2
3
30
30
99
99
6.6
4
5
10
30
99
99
19.8
6.6
6.6
6
30
99
7
8
30
30
99
84
6.6
5.6
22

9
30
99
82
6.6
10
100
1.64
11
12
60
99
99
3.3
120
1.65
13
180
99
1.10
14
15
180
260
99
99
1.10
0.76
Reaction conditions: Aryl bromide (1 mmol), phenylboronic acid (1.1 mmol), Pd catalyst 7
(0.5 mol%), K2CO3 (1 mmol) using methanol as solvent at 70 C.
To further establish the efficiency of present catalyst system, we carried out a reaction between
4-bromobenzoyl chloride and phenylboronic acid in order to effect both the coupling reactions
in a one pot using the palladium complex 4 as catalyst. The reactions afforded the expected
coupled product in 89 % of yield with the turnover frequency of 0.64 min-1.
Scheme 4. One pot coupling reaction of 4-bromobenzoyl chloride with phenylboronic acid
23

4. Conclusion
In conclusion, thiazoline/imidazoline derived ligands, 2-(4,5-dihydrothiazol-2-yl)aniline (2)
and 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (3) exhibits versatile coordination behavior with
palladium precursor which lead to the isolation of mononuclear complexes containing NN
and NS as coordinating atoms. The newly synthesized palladium complexes
PdCl2{2N,S2(4,5-dihydrothiazol-2-yl)aniline} (4) and PdCl2{2N,N’(4,5-dihydro-1H-
imidazol-2-yl)aniline} (7), respectively, were found to be efficient catalyst for both the
coupling reactions of acid chlorides with arylboronic acids to access aryl ketones and aryl
bromides with phenylboronic acid to produce biaryls. The catalysts were found to tolerate both
electron-rich and electron-deficient systems and afforded the coupled products in good to
excellent yields. Further utilization of these complexes as catalysts for other palladium
mediated coupling reactions are under active investigation in our laboratory.
Supporting Information
Spectroscopic data for all the compounds (2 – 9) and the selected coupled products are given
in the supporting information.
Acknowledgement
DS thanks the Department of Science and Technology (DST), India for the financial supports
through the project YSS-2014-000217.
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27

Synthesis and Palladium(II) Metal Chemistry of Thiazoline/Imidazoline Derived
Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylboronic Acids with
Acid Chlorides and Aryl Halides
Murugesan Sudharsan and D. Suresh*
Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed
University, Thanjavur, Tamil Nadu, 613 401, India
Graphical Abstract
Synthesis and Palladium(II) Metal Chemistry of Thiazoline/Imidazoline Derived
Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylboronic Acids with
Acid Chlorides and Aryl Halides
Murugesan Sudharsan and D. Suresh*
28

Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed
University, Thanjavur, Tamil Nadu, 613 401, India
Highlights
 Thiazoline/imidazoline derived ligands exhibit versatile coordination behavior with
palladium precursor which lead to the isolation of mononuclear complexes containing
NN and NS as coordinating atoms.
 Palladium complexes are found to be efficient catalyst for both the coupling reactions
of acid chlorides with arylboronic acids to access dissymmetric ketones and aryl
bromides with phenylboronic acid to produce biaryls.
1
 Turn over frequency is upto 19.8 min .
Synthesis and Palladium(II) Metal Chemistry of Thiazoline/Imidazoline Derived
Ligands: An Efficient Catalyst for Cross-Coupling Reactions of Arylboronic Acids with
Acid Chlorides and Aryl Halides
Murugesan Sudharsan and D. Suresh*
Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed
University, Thanjavur, Tamil Nadu, 613 401, India
Graphical Abstract
29