Synthesis, characterization and microwave-assisted catalytic activity of novel benzimidazole salts bearing piperidine and morpholine moieties in Heck cross-coupling reactions

Article abstract of DOI:10.1002/aoc.1751

A mixture of novel benzimidazole salts (2a-f), Pd(OAc)₂ and K₂CO₃ in DMF-H₂O catalyzes, in high yield, the Heck cross-coupling reaction assisted by microwave irradiation in a short time. All synthesized novel benzimidazole derivatives were characterized by elemental analysis and NMR spectroscopy. In addition, the molecular structure of 2a was determined by X-ray crystallography.

Full text of DOI:10.1002/aoc.1751

Full Paper
Received: 12 July 2010
Revised: 14 September 2010
Accepted: 15 September 2010
Published online in Wiley Online Library: 14 January 2011
(wileyonlinelibrary.com) DOI 10.1002/aoc.1751
Synthesis, characterization
and microwave-assisted catalytic activity
of novel benzimidazole salts bearing
piperidine and morpholine moieties in Heck
cross-coupling reactions
a∗
b
a
c
¨
Hasan Ku¨c¸u¨kbay , Nihat S¸ireci , Ulku¨ Yılmaz , Mehmet Akkurt ,
S¸erife Pınar Yalc¸ınd, M. Nawaz Tahire and Holger Ottf
A mixture of novel benzimidazole salts (2a–f), Pd(OAc)2 and K2CO3 in DMF–H2O catalyzes, in high yield, the Heck cross-
coupling reaction assisted by microwave irradiation in a short time. All synthesized novel benzimidazole derivatives were
characterized by elemental analysis and NMR spectroscopy. In addition, the molecular structure of 2a was determined by X-ray
c
crystallography. Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: benzimidazole salt; carbene; palladium catalysis; coupling reaction; Heck coupling; microwave
Introduction
Heck reactions.[17–18] Although there are extensive studies on
thePd(OAc)2/substituted-benzimidazoleorsubstituted-imidazole
catalytic systems in Heck cross-coupling reactions, much less at-
tention has been paid to the benzimidazole ligands containing
piperidine and morpholine moieties in these systems.[19–21] The
combination of the benzimidazole and piperidine or morpholine
heterocycles as ligands may be a good opportunity to obtain
better results in Heck cross-coupling reactions.
On the other hand, high-speed synthesis with microwaves
has attracted considerable attention in recent years. The use
of metal catalysts in conjunction with microwaves may have
significant advantages over traditional heating methods since
the inverted temperature gradient under microwave conditions
may lead to an increased lifetime of catalyst through elimination
The Mizoroki–Heck reaction is one of the most widely used
palladium-catalyzed C–C coupling reactions in organic synthesis,
polymerization processes, UV screens, pharmaceuticals, prepara-
tion of hydrocarbons, and in advanced enantioselective synthesis
of natural products.[1–5] The traditional Heck reaction is typically
performed with 1–5 mol% of a palladium catalyst along with
phosphine ligands in the presence of a suitable base. However,
inert reaction conditions must be provided due to the ligands
applied (especially for electron-rich phosphine ligands), which
are often toxic and sensitive to air and moisture.[6,7] Because
of their strong σ-donor character and low toxicity, the use of
N-heterocyclic carbenes (NHCs) as alternative ligands to phos-
phine ligands in palladium-catalyzed cross-coupling reactions is
recommended.[8–12] Pd(II)–NHC complexes are more attractive as
pre-catalysts because of their stability to air, moisture and heating
and also have an excellent long-term storage profile.[13]
∗
¨
Correspondence to: Hasan Ku¨c¸u¨kbay, Inonu¨ University, Faculty Science and
Arts, Department of Chemistry, 44280 Malatya, Turkey.
E-mail: hkucukbay@inonu.edu.tr
The ligand-free systems consist of Pd(OAc)2 or Pd(O2CCF3)2;
base and solvents have also been used as a catalyst system in Heck
coupling reactions.[7,14,15] However, using the Pd(OAc)2 catalytic
systems containing ligands has been shown more effective
catalytic activity than ligand-free palladium containing systems.
The base-free systems consist of arylboronic acid as arylpal-
ladium precursors, Pd(OAc)2, 2,9-dimethyl-1-10-phenanthroline
(dmphen)astheregiocontrollingligand,p-benzoquinoneoratmo-
sphericairasareoxidant,anddifferentsolventssuchasacetonitrile
or deionized water have also been used as an efficient catalyst
system in Heck coupling reactions.[16]
¨
a
Inonu¨ University, Faculty Science and Arts, Department of Chemistry, 44280
Malatya, Turkey
b
c
Adıyaman University, Faculty Education, 02040 Adıyaman, Turkey
Erciyes University, Faculty Science and Arts, Department of Physics, 38039
Kayseri, Turkey
d
Harran University, Faculty Science and Arts, Department of Physics, 63300
S¸anlıurfa, Turkey
e
f
University of Sargodha, Department of Physics, Pakistan
Pd(OAc)2 –benzimidazole or imidazole ligands could be
very effective catalytic systems, particularly in Suzuki and
Bruker AXS GmbH, Oestliche Rheinbrueckenstrasse 49, 76187, Karlsruhe,
Germany
c
Appl. Organometal. Chem. 2011, 25, 255–261
Copyright ꢀ 2011 John Wiley & Sons, Ltd.

H. Ku¨c¸u¨kbay et al.
of wall effects.[6,13,22]. The C–C cross-coupling in Heck reactions
has also been carried out in quite short times resulting in high
yields.[18,23–28]
144.4 (NCHN), 144.0, 136.4, 134.3, 132.9, 129.1, 128.4 (C6H4), 126.9,
125.2, 122.8, 122.0 (C6H5-cinnamyl), 120.0, 111.2 (CH CH–C6H5),
46.7 (CH2 –CHCHC6H5).
Herein, we describe the synthesis of new benzimidazole (1a)
and benzimidazole salts (2a–d and f) containing piperidine and
morpholine moieties. The compounds were fully characterized by
elemental analysis, IR, 13C NMR and 1H NMR spectroscopy and the
molecularstructureof2awasdeterminedbyX-raycrystallography.
We also report on the microwave-assisted catalytic activity
of Pd(OAc)2/benzimidazole salts (2a–f) in Heck cross-coupling
reactions.
Synthesis of 1-cinnamyl-3-[2-(piperidinium-1-yl)ethyl]
benzimidazolium dichloride dihydrate 2a
A mixture of 1-cinnamylbenzimidazole (1.17 g, 5 mmol) and
1-(2-chloroethyl)piperidine monohydrochloride (0.92g, 5 mmol)
in dimethylformamide (5 ml) was refluxed for 4 h. Volatiles
were removed in vacuo and the residue was crystallized from
EtOH–DMF(3 : 1).Yellowcrystalsof2a(1.64 g,78%)wereobtained.
M.p. 253–254 ◦C. υ(N C): 1558 cm−1, υ(C C): 1640 cm−1. Anal.
found:C, 60.63;H, 7.29;N, 9.18;calcdforC23H33N3Cl2O2, C, 60.79;H,
7.32;N,9.25%.1HNMR(δ,DMSO-d6):11.59(s,1H,NH-piperidinium),
10.09 (s, 1H, NCHN), 8.28–7.72 (m, 4H, C6H4), 7.50, 7.37 (m, 5H,
C6H5-cinnamyl), 7.01 (d, 1H, CH CH–C6H5, 3JH,H = 15.9 Hz), 6.67
(dt, 1H, CH CH–C6H5, 3JH,CH2 = 6.6 Hz), 5.36 (d, CH2 –CHCHC6H5,
3J = 6.6 Hz), 5.09 (t, 2H, CH2CH2-piperidine, 3J = 6.0 Hz), 3.65 (m,
Experimental
All preparations were carried out in inert atmosphere of
argon using standard Schlenk techniques. Starting materials and
reagents used were of commercial grade and purchased from
Aldrich or Merck Chemical Co. Solvents were dried with standard
methods and freshly distilled prior to use. All catalytic activity
experiments were carried out in a microwave oven manufactured
by Milestone (Milestone Start S Microwave Labstation for
Synthesis) under aerobic conditions. 1H-NMR (300 MHz) and 13C-
NMR (75 MHz) spectra were recorded using a Bruker DPX-300
high-performance digital FT NMR spectrometer. Infrared spectra
were recorded from KBr pellets in the range 4000–400 cm−1 on
a Perkin-Elmer FT-IR spectrophotometer. Elemental analyses were
performed with a Leco CHNS-932 elemental analyzer. Melting
points were recorded using an electrothermal-9200 melting point
apparatus, and are given uncorrected.
3
4H, ring methylene), 3.00 (t, 2H, CH2CH2-piperidine, J = 6 Hz),
1.81 (m, 4H, ring methylene), 1.43 (m, 2H, ring methylene). 13C
NMR (δ, DMSO-d6): 144.0 (NCHN), 136.1, 135.5, 131.6, 131.6, 129.2,
128.9 (C6H4), 127.2, 127.1, 127.0, 122.4 (C6H5-cinnamyl), 114.4,
114.4(CH CH–C6H5), 53.8(CH2 –CHCHC6H5), 52.6, 49.2(CH2CH2-
piperidine), 41.4, 22.44, 21.7 (ring methylene).
Similarly, 1-(4-methylbenzyl)-3-[2-(piperidinium-1-yl)ethyl]ben-
zimidazolium dichloride, 2b, 1-(4-chlorobenzyl)-3-[2-(piperidi-
nium-1-yl)ethyl]benzimidazolium dichloride, 2c, 1-(4-chloroben-
zyl)-3-[2-(morpholinium-1-yl)ethyl]benzimidazolium dichloride,
2e and 1-benzyl-3-[2-(morpholinium-1-yl)ethyl]benzimidazolium
dichloride, 2f were synthesized from 1-(4-methylbenzyl)ben-
zimidazole with 1-(2-chloroethyl)piperidine monohydrochloride,
1-(4-chlorobenzyl)benzimidazole with 1-(2-chloroethyl)piperidine
monohydrochloride, 1-(4-chlorobenzyl)benzimidazole with 1-(2-
chloroethyl)morpholine monohydrochloride and 1-benzylben-
zimidazolewith1-(2-chloroethyl)morpholinemonohydrochloride,
respectively.
1-Substituted benzimidazoles (1b–d[29–31] and 2d[32]) that
are used in this work as a starting compounds were prepared
according to literature procedures. There is little information
about compound 1a,[33] so full information for compound 1a is
given in this report.
GC-MS Analysis
GC-MS spectra were recorded on an Agilient 6890 N GC and
5973 Mass Selective Detector with a HP-INNOWAX column of
60 m length, 0.25 mm diameter and 0.25 µm film thicknesses.
GC-MS parameters for Heck coupling reactions were as follows:
initial temperature, 60 ◦C; initial time, 5 min; temperature ramp
1, 30 ◦C/min; final temperature, 200 ◦C; ramp 2, 20 ◦C/min; final
temperature 250 ◦C; run time 30.17 min; injector port temperature
250 ◦C; detector temperature 250 ◦C, injection volume, 1.0 µl;
carrier gas helium; mass range between m/z 50 and 550.
1-(4-Methylbenzyl)-3-[2-(piperidinium-1-yl)ethyl]benzimidazolium
dichloride, 2b
Yield 1.87 g, 83%, yellow. M.p. 210–211 ◦C; υ(N C): 1557 cm−1
.
Anal. found: C, 58.22; H, 6.35; N, 9.16%; calcd for C22H29N3ClBr:
C, 58.61; H, 6.48; N, 9.32. 1H NMR (δ, DMSO-d6): 11.67 (s, 1H, NH-
piperidinium), 10.38 (s, 1H, NCHN), 8.30–7.68 (m, 4H, C6H4), 7.50,
7.23 (m, 4H, xylyl), 5.78 (s, 2H, CH2 –C6H4), 5.16 (t, 2H, CH2CH2-
3
piperidine, J = 6 Hz), 3.67 (m, 4H, ring methylene), 3.06 (t, 2H,
3
CH2CH2-piperidine, J = 6 Hz), 2.30 (s, 3H, CH3 –C6H4), 1.82 (m,
4H, ring methylene), 1.43 (m, 2H, ring methylene). 13C NMR (δ,
DMSO-d6): 144.05 (NCHN), 138.6, 138.6, 131.6, 131.3, 130, 129.1
(C6H4), 129.0, 127.1, 127.1, 114.5 (xylyl), 53.54 (CH2 –C6H4), 52.62,
50.32 (CH2CH2-piperidine), 41.52, 22.75, 21.70 (ring methylene),
21.21 (CH3 –C6H4).
Synthesis of 1-cinnamylbenzimidazole, 1a
Cinnamyl chloride (2.4 ml, 17.2 mmol) was added to a solution of
benzimidazole (2.00 g; 16.9 mmol) and KOH (1.89 g, 33.8 mmol)
in EtOH (20 ml) and the mixture was heated under reflux for 4 h.
The mixture was then cooled and the resulted potassium chloride
was filtered off and washed with a portion of EtOH. Volatiles were
removed in vacuo and the residue was crystallized from EtOH.
White crystals of 1a (3.29 g, 83%) were obtained. M.p. 104–105 ◦C.
υ(N C): 1563 cm−1), υ(C C): 1670 cm−1. Anal. found: C, 81.96; H,
6.02; N, 11.92%; calcd for C16H14N2: C, 82.02; H, 6.02; N, 11.96. 1H
NMR (δ, DMSO-d6): 8.30 (s, 1H, NCHN), 7.70–7.44 (m, 4H, C6H4),
7.34–7.19 (m, 5H, C6H5-cinnamyl), 6.65 (d, 1H, CH CH–C6H5,
1-(4-Chlorobenzyl)-3-[2-(piperidinium-1-yl)ethyl]benzimidazolium
dichloride, 2c
Yield 1.82 g, 85%, white. M.p. 261–262 ◦C; υ(N C): 1556 cm−1
.
Anal. found: C, 59.02; H, 6.04; N, 9.71%; calcd for C21H26N3Cl3: C,
59.10; H, 6.14; N, 9.85. 1H NMR (δ, DMSO-d6): 11.62 (s, 1H, NH-
piperidinium), 10.27 (s, 1H, NCHN), 8.27–7.73 (m, 4H, C6H4), 7.66,
7.52 (m, 4H, benzyl), 5.81 (s, 2H, CH2 –C6H4Cl), 5.11 (t, 2H, CH2CH2-
piperidine, 3J = 6.3 Hz), 3.60 (m, 4H, ring methylene), 3.03 (t, 2H,
3
3JH,H = 15.9 Hz), 6.51 (dt, 1H, CH CH–C6H5, JH,CH2 = 6.0 Hz),
5.08 (d, CH2 –CHCHC6H5, 3J = 6.0 Hz). 13C NMR (δ, DMSO-d6):
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 255–261

Novel benzimidazole salts bearing piperidine and morpholine moieties
Cl-
Y
+
N
Cl
H
2a Y = CH2, R = cinnamyl
2b Y = CH2, R = p-xylyl
2c Y = CH2, R = p-chlorobenzyl
2d Y = CH2, R = benzyl
R
N
+
Y = CH2, O
R
N
H
N
DMF
KOH, RX, EtOH
-
N
2Cl
N
N
1a R = cinnamyl
+
N
H
1b R = p-xylylbenzyl
1c R = p-chlorobenzyl
1d R = benzyl
2e Y = O, R = p-chlorobenzyl
2f Y = O, R = benzyl
Y
Scheme 1. Synthesis pathway of benzimidazole derivatives.
CH2CH2-piperidine, 3J = 6.3 Hz), 1.81 (m, 4H, ring methylene),
1.44 (m, 2H, ring methylene). 13C NMR (δ, DMSO-d6): 144.28
(NCHN), 133.94, 133.22, 131.65, 131.39, 130.91, 129.45 (C6H4),
129.35, 127.20, 127.15, 114.52 (benzyl), 53.57 (CH2 –C6H4), 52.66,
49.75 (CH2CH2-piperidine), 41.52, 22.50, 21.72 (ring methylene).
Initial hydrogen atom positions of the lattice solvents were located
in a difference Fourier map and refined using restraints for an
idealized water molecule. The remaining hydrogen atoms were
placed in calculated positions (C–H 0.95–0.99 Å, N–H = 0.93 Å)
andincludedintherefinementusing theriding model, with Uiso(H)
= 1.2 or 1.5 Ueq (N, C). A summary of the crystal data, experimental
details and refinement results for 2a is given in Table 1. The
hydrogen bond and molecular packing geometry of compound
2awerecalculatedwithPLATON.[37] Thegraphicalrepresentations
of the structure were made with ORTEP.[38]
1-(4-Chlorobenzyl)-3-[2-(morpholinium-1-yl)ethyl]benzimidazolium
dichloride, 2e
Yield 1.55 g, 72%, white. M.p. 163–164 ◦C. υ(N C): 1561 cm−1
.
Anal. found: C, 55.57; H, 5.33; N, 9.52%; calcd for C20H24N3Cl3O:
C, 56.02; H, 5.64; N, 9.80. 1H NMR (δ, DMSO-d6): 12.23 (s, 1H,
NH-morpholinium), 10.40 (s, 1H, NCHN), 8.16–7.67 (m, 4H, C6H4),
7.62 and 7.50 (m, 4H, benzyl), 5.95 (s, 2H, CH2 –C6H4), 4.71 (t, 2H,
General Procedure for the Heck Reactions
Pd(OAc)2 (1 mmol%), benzimidazolium chlorides (2a–f;
2 mmol%), the aryl halide (1 mmol), styrene (1.2 mmol), K2CO3
(4 mmol), water (3 ml) and DMF (3 ml) were added to microwave
apparatus and the mixture was heated at 80 ◦C (300 W) for 10 min.
It was carried out over a ramp time of 3 min to reach to 80 ◦C
temperature. At the end of reaction, the mixture was cooled, the
product was extracted with ethyl acetate–n-hexane (1 : 5) and pu-
rified on a silica gel column. The purity of coupling products was
checked by NMR and GC-MS, and the reported yields are based on
aryl halide.
3
CH2CH2-morpholine, J = 5.4 Hz), 3.48 (m, 4H, ring methylene),
3
2.77 (t, 2H, CH2CH2-morpholine, J = 5.4 Hz), 2.44 (m, 4H, ring
methylene). 13C NMR (δ, DMSO-d6): 143.6 (NCHN), 133.9, 133.5,
131.7, 131.4, 131.0, 129.4 (C6H4), 129.4, 127.2, 127.1, 114.4 (benzyl),
66.6 (CH2 –C6H4), 56.1, 53.3 (CH2CH2-morpholine), 49.7, 44.0 (ring
methylene).
1-Benzyl-3-[2-(morpholinium-1-yl)ethyl]benzimidazolium
dichloride, 2f
Yield 1.50 g, 76%, white. M.p. 209–210 ◦C. υ(N C): 1557 cm−1
.
Anal. found: C, 60.68; H, 6.32; N, 10.47%; calcd for C20H25N3Cl2O:
1
Results and Discussion
C, 60.92; H, 6.39; N, 10.66%. H NMR (δ, DMSO-d6): 12.31 (s, 1H,
NH-morpholinium), 10.40 (s, 1H, NCHN), 8.25–7.72 (m, 4H, C6H4),
7.64, 7.42 (m, 4H, benzyl), 5.81 (s, 2H, CH2 –C6H4), 5.11 (t, 2H,
CH2CH2-morholine, 3J = 6.9 Hz), 3.47 (m, 4H, ring methylene),
In this work, benzimidazolium chloride salts, which are
conventional NHC precursors, containing piperidine and
morpholine heterocycles, 2a–f, were used. These salts were
prepared from the treatment of 1-alkylbenzimidazoles (1a–d)
with 1-(2-chloroethyl)piperidine monohydrochloride or 1-(2-
chloroethyl)morpholinemonohydrochlorideinrefluxingDMFwith
good yields of 72–85%. The synthesis of the benzimidazoles 2a–f
is summarized in Scheme 1. The benzimidazolium salts are air and
moisture-stable in the solid state as well as in solution. The 2a–f
were identified by spectroscopic methods and elemental analysis.
3
2.83 (t, 2H, CH2CH2-morpholine, J = 6.9 Hz), 2.47 (m, 4H, ring
methylene). 13C NMR (δ, DMSO-d6): 144.3 (NCHN), 134.6, 134.4,
131.6, 131.5, 129.5, 129.0, (C6H4), 128.8, 127.2, 127.1, 114.4(benzyl),
63.6 (CH2 –C6H4), 53.9, 51.9 (CH2CH2-morpholine), 50.5, 41.4 (ring
methylene).
Single-crystal X-ray diffraction analysis of 1-cinnamyl-3-[2-
(piperidinium-1-yl)ethyl]benzimidazolium dichloride dihydrate, 2a
1
The NCHN δ[13C{ H}] signal of the benzimidazolium salts is usually
The X-ray data were collected on a Bruker X8 Prospector system
equipped with a highly sensitive APEX II area detector and using
an IµS X-ray microfocus source with multilayer mirrors, that
give intense monochromatic CuKα radiation (λ = 1.54178 Å).
An empirical absorption correction was applied during the data
processing using SADABS.[34] The structure was solved by direct
methods using SHELXS[35] and refined using the SHELXL-97.[36]
around 142 4 ppm.[39] For the benzimidazolium salts 2a–f it was
found to be 144.0, 144.0, 144.0, 143.6 and 144.3 ppm, respectively.
These values are in good agreement with the previously reported
results.[18,40,41] The NCHN protons of the benzimidazolium salts
were observed as singlet in the 1H NMR spectrum at 10.09, 10.38,
10.27, 10.46 and 10.40 ppm, respectively. These chemical shift
values are typical for NCHN protons of benzimidazolium salts
c
Appl. Organometal. Chem. 2011, 25, 255–261
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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H. Ku¨c¸u¨kbay et al.
The benzimidazole derivatives 2a–f show IR absorption bands
at 1558, 1557, 1556, 1561 and 1557 cm−1, respectively, which
are assigned to ν(C N). These IR absorption values are in good
agreement with previously reported values for benzimidazolium
salts.[17–18] These values are slightly smaller than expected for a
standard ν(C N) because of the π-electron delocalization on the
imidazolium ring.
Molecular Structure of 1-Cinnamyl-3-[2-(piperidinium-1-yl)
ethyl]benzimidazolium Dichloride Dihydrate, 2a
The title compound, 2a (Fig. 1), crystallizes in the monoclinic
spacegroupPc,withtwo1-cinnamyl-3-[2-(piperidinium-1-yl)ethyl]
benzimidazolium cations, four chloride anions and four water
molecules in the asymmetric unit.
The benzimidazole rings (N1/N2/C1–C7 and N4/N5/C24–C30)
of both cations are planar with maximum deviations of 0.028(2)
and 0.025(3) Å, respectively. The dihedral angle between them is
1.64(8)◦. The phenyl rings (C18–C23 and C41–C46) form dihedral
angles of 73.45(11) and 74.66(12)◦ with the respective benzim-
idazole ring. As expected, the two piperidinium rings of both
cations exhibit a chair conformation [puckering parameters[45] are
QT = 0.581(3) Å, θ = 180.0 (3)◦ and φ = 345 (21)◦ for the ring
(N3/C10–C14) and QT = 0.569(3) Å, θ = 0.0 (3)◦ and φ = 210
(25)◦ for the ring (N6/C33–C37)].
Scheme 2. Open line structure of 2a.
· · ·
· · ·
· · ·
The crystal structure shows N–H Cl, N–H O, O–H Cl,
because of their increased acidity.[18,40–43] In comparison, the cor-
responding value of the starting material 1a is 8.30 ppm, which is
significantly smaller than in benzimidazolium salts. The cinnamyl
substituents of 1a and 2a (Scheme 2) display a trans arrangement,
which is also reflected in the proton NMR spectra. The coupling
constant of the protons connected to the C C double bond
are both 15.9 Hz, which is a typical value for protons in a trans
arrangement.[44]
· · ·
· · ·
C–H Cl and C–H O interactions (Table 2 and Fig. 2). A weak
· · ·
C–H π-interaction may also be present.
The Heck coupling reaction
The Mizoroki–Heck reaction, the coupling of aryl halides with
terminal olefins, ranges among the most important palladium-
catalyzed transformations in organic synthesis.[46] The rate of
Figure 1. Molecular structure of 2a including atom labels. The anisotropic displacement parameters are displayed at a 50% probability level.
c
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2011, 25, 255–261

Novel benzimidazole salts bearing piperidine and morpholine moieties
Table 1. Crystal data and structure refinement details for 2a
Table 2. Hydrogen-bond parameters (Å, deg)
D–
Crystal data
· · ·
· · ·
· · ·
D–H
H
A
D
A
H
A
C23H29N3.2(H2O).2(Cl)
Z = 4
· · ·
N3–HN3 Cl4
0.9300
0.9300
0.84 (2)
0.85 (2)
0.82 (2)
0.823 (17)
0.823 (19)
0.83 (2)
0.9500
0.9500
0.9500
0.9900
0.9900
0.9500
0.9500
0.9500
0.9500
0.9900
0.9900
0.9900
0.9900
0.99
2.1500
1.9200
2.36 (2)
2.35 (2)
2.32 (2)
2.356 (17)
2.336 (18)
2.30 (2)
2.3100
2.3800
2.3000
2.6800
2.6000
2.8200
2.6700
2.3100
2.4900
2.8100
2.8300
2.7100
2.8000
2.73
3.082 (2)
2.774 (3)
3.165 (3)
3.190 (4)
3.135 (2)
3.179 (2)
3.148 (2)
3.122 (2)
3.210 (3)
3.066 (3)
3.072 (3)
3.643 (3)
3.557 (3)
3.694 (3)
3.552 (3)
3.077 (3)
3.127 (3)
3.655 (3)
3.770 (3)
3.523 (3)
3.687 (3)
3.460 (3)
177.00
151.00
161 (3)
168 (3)
169 (3)
178 (4)
169 (4)
171 (2)
158.00
129.00
138.00
166.00
162.00
153.00
154.00
137.00
125.00
143.00
160.00
140.00
150.00
130
Mr = 454.42
Dx = 1.308 Mg m−3
Cu Kα radiation
· · ·
N6–HN6 OW1
Monoclinic, Pc
i
· · ·
OW1–H101 Cl1
a = 16.1852 (5) Å
b = 20.8616 (7) Å
c = 6.8484 (2) Å
β = 93.927 (1)◦
V = 2306.93 (12) Å3
· · ·
OW1–H102 Cl1
· · ·
OW2–H103 Cl2
µ = 2.72 mm−1
T = 100 K
· · ·
OW2–H104 Cl3
· · ·
OW3–H105 Cl2
Crystal shape block, color light
yellow Crystal dimensions:
0.2 × 0.2 × 0.2 mm3
· · ·
OW3–H106 Cl3
ii
· · ·
C5–H5 OW4
iii
· · ·
C7–H7 OW2
Data collection
· · ·
C7–H7 OW3
X8 Prospector diffractometer
ω and φ scans
Rint = 0.050
iii
θmax = 67.6◦
h = −19 → 19
· · ·
C8–H8A Cl3
· · ·
C15–H15A Cl2
Absorption correction: multi-scan
(based on symmetry-related
measurements)
i
· · ·
C27–H27 Cl2
i
· · ·
C28–H28 Cl1
C30–H30· · ·OW2iii
T
min/Tmax = 0.99
k = −22 → 24
l = −7 → 8
26510 measured reflections
7136 independent reflections
7110 reflections with I > 2σ(I)
· · ·
C30–H30 OW3
· · ·
C31–H31B Cl2
· · ·
C33–H33A Cl1
iii
· · ·
C37–H37B Cl1
Refinement
Refinement on F2
iii
· · ·
C38–H38B Cl3
Calculated weights
w = 1/[σ2(Fo2) +
· · ·
iv
C12–H12A Cg9
(0.0895P)2 + 0.5424P] where
P = (Fo + 2Fc2)/3
2
Symmetry codes: (i) x, 1 − y, 1/2 + z; (ii) x, −y, 1/2 + z; (iii) x, y,
1 + z; (iv) x, y, z.
R[F2 > 2σ(F2)] = 0.046
wR(F2) = 0.121
S = 1.04
(ꢀ/σ)max <0.0001
ꢀρmax = 0.35 e Å−1
ꢀρmin = −0.54 e Å−1
Extinction correction: none
7136 reflections
566 parameters
Absolute structure: Flack (1983),
2952 Freidel pairs
Mixture of independent and
Flack parameter: 0.141 (11)
constrained H-atom refinement
the coupling is dependent on a variety of parameters such as
the base, the solvent, the temperature and the nature of the
catalyst loading. We recently reported optimal reaction conditions
for Heck coupling reactions, including bis-benzimidazolium salts
and Pd(OAc)2, in basic environment under microwave and
conventional heating conditions.[18] In the present report, a
series of aryl bromide and chloride compounds bearing electron-
deficient substituents and aryl iodide were used for the coupling
reactionwithstyrene.Therecentlyreportedoptimalparameters[18]
were slightly modified (80 ◦C/300 W) Since there are two acidic
protons on benzimidazolium salts (2a–f) and protons on N atoms
of piperidine or morpholine are more acidic than the proton of
2-position of the benzimidazole ring, which N-heterocyclic carben
precursors (NCHN), we used 4% mol of base to remove both acidic
protons of benzimidazolium dihalides. Finally, we found that 1%
mol Pd(OAc)2, 2% mol of 2a–f, 4% mol of K2CO3 in DMF–H2O
(1 : 1)at80 ◦C/300 Wmicrowaveheating ledtothebestconversion
within 10 min. It has been observed that no increase in catalytic
reactions yield is found by prolonging reaction time from 10
to 20 min (Table 3, entry 2). Furthermore, no coupling reaction
occurred in the absence of 2a within 5 min (Table 3, entry 3) and
very low yield was detected within 10 min (Table 3, entry 4). We
also tested the catalytic yield using a conventional heating system
Figure 2. Packing diagram (unit cell shown) and hydrogen bonding of
2a. Hydrogen bonds are indicated as dashed lines. Hydrogen atoms not
involved in hydrogen bonding are omitted for clarity.
(i.e. preheated oil bath) after 10 and 20 min at 80 ◦C and the yields
were detected 17 and 48%, respectively (Table 3, entries 5 and 6).
A complete list of the results obtained with optimal conditions
is given in Table 3. Altogether five different aryl halides bearing
electron-donating and electron-withdrawing groups reacted with
styrene and gave the coupled products in high yield. As expected,
the yields of the Heck coupling reactions with styrene and aryl
chlorides with electron-deficient substituents were found to be
very high. It is noteworthy that aryl chlorides are the most useful
substrates because their costs are low and they are commercially
available.[47]
c
Appl. Organometal. Chem. 2011, 25, 255–261
Copyright ꢀ 2011 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

H. Ku¨c¸u¨kbay et al.
particles in the reaction mixture, which are probably palladium
nanoparticles. The reactivity of the aryl halide component on Heck
coupling reactions decreases in the order I > Br > Cl, which is
in good agreement with previous reports.[19] However, the Heck
coupling reaction with aryl chlorides with electron withdrawing
substituents did not give a detectable amount of Heck coupling
products in conventional heating systems.[19,48] On the contrary
good yields were obtained for all aryl halides with styrene using
the microwave heating system (Table 3).
Table 3. Heck coupling reactions of aryl halides with styrene
Y
Pd(OAc)2 (1 mol %)
R
2a-2f (2 mol %), mw (300 W)
X
+
R
DMF/ H2O (1:1), 80 °C, 10 min
K2CO3 (4 equiv)
Y
Entry
Y
R
X
Salt
Yield (%)
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
I
I
2a
2a
no
no
2a
2a
2a
2b
2c
2d
2e
2f
76a
99b
n.dc
09d
17e
48f
99
99
97
98
95
96
97
97
95
96
93
95
97
96
95
96
93
95
99
99
97
99
94
96
93
93
89
91
85
2
3
H
I
Conclusions
4
H
I
5
H
I
We prepared five benzimidazolium salts bearing piperidine
and morpholine substituents (2a–f) from 1-substituted benz-
imidazoles (1a–d) and corresponding piperidine or morpholine
chlorides. The use of palladium catalyst systems including ben-
zimidazole salts in the Heck reactions gives better yields under
microwave-assisted moderate conditions and very short reaction
times compared with those given in literature.[19] The Heck reac-
tions were carried out using 300 W power microwave irradiation
at 80 ◦C in only 10 min. It can be concluded that Heck coupling
reactions may be accelerated by microwave irradiation even if
aryl chlorides bearing electron-withdrawing nitro substituents,
contrary to some literature information.[19,49–51]
6
H
I
7
H
I
8
H
I
9
H
I
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
H
I
H
I
H
I
H
OCH3
OCH3
OCH3
OCH3
OCH3
OCH3
CH3
I
2a
2b
2c
2d
2e
2f
H
I
H
I
H
I
H
I
H
I
CH3
CH3
CH3
CH3
CH3
CH3
H
I
2a
2b
2c
2d
2e
2f
Acknowledgments
CH3
I
This work was financially supported by the Ino¨nu¨ University
CH3
I
¨
Research Fund (IU BAP 2008/59 and 2008/60).
CH3
I
CH3
I
CH3
I
COCH3
COCH3
COCH3
COCH3
COCH3
COCH3
NO2
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
Cl
Cl
2a
2b
2c
2d
2e
2f
Supporting Information
H
Supporting information can be found in the online version
of this article. CCDC holds the supplementary crystallographic
data 782253. These data can be obtained free of charge
via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the
Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; Fax (+44) 1223-336-033; or email de-
posit@ccdc.cam.ac.uk.
H
H
H
H
H
2a
2b
2c
2d
2e
H
NO2
H
NO2
H
NO2
H
NO2
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min with thermal heating. n.d., Not detected.
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Copyright ꢀ 2011 John Wiley & Sons, Ltd.
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