Short synthesis of bis-NHC-Pd catalyst derived from caffeine and its applications to Suzuki, Heck, and Sonogashira reactions in aqueous solution

Article abstract of DOI:10.1016/j.jorganchem.2010.11.002

A short and efficient synthesis of a bis-NHC-palladium catalyst simply prepared from caffeine in two steps was reported. The air and moisture stable Pd catalyst can be used as a good catalyst in running Suzuki-Miyaura, Mizoroki-Heck, and Sonogashira react

Full text of DOI:10.1016/j.jorganchem.2010.11.002

Journal of Organometallic Chemistry 696 (2011) 1262e1265
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Short synthesis of bis-NHC-Pd catalyst derived from caffeine and its applications
to Suzuki, Heck, and Sonogashira reactions in aqueous solution
*
Fen-Tair Luo , Hung-Kun Lo
Institute of Chemistry, Academia Sinica, Nankang, Taipei 11529, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A short and efficient synthesis of a bis-NHC-palladium catalyst simply prepared from caffeine in two
steps was reported. The air and moisture stable Pd catalyst can be used as a good catalyst in running
SuzukieMiyaura, MizorokieHeck, and Sonogashira reactions in aqueous solution.
Ó 2010 Elsevier B.V. All rights reserved.
Received 29 September 2010
Received in revised form
2 November 2010
Accepted 2 November 2010
Keywords:
Suzuki reaction
Heck reaction
Sonogashira reaction
bis-NHC-Pd complex
Caffeine
NHC
1. Introduction
bis-NHC-Pd catalyst derived from caffeine in two steps and its
application to cross-couplings such as SuzukieMiyaura Mizorokie
The development of N-heterocyclic carbene (NHC), derived from
the 1,3-disubstituted imidazolium salt, have been attracted
a significant amount of research attention as a new class of ligand in
homogeneous catalysts used in avariety of metal-mediated catalytic
reactions [1e9]. In addition to their air and moisture stabilities, the
Heck, and Sonogashira reactions in water with or without additives.
2. Results and discussion
The synthesis of the bis-NHC-Pd catalyst is shown in Scheme 1.
Caffeine was reacted with excess of methyl iodide in dry DMF at
100 ꢀC for 20 h. An excess amount of dry ethyl acetate was added to
good s-donating property of NHC could form stronger bonds with
most metals compared with phosphine ligands [10e13]. The elec-
tron richness of NHC may influence various reactions, such as
oxidative addition [9,14e23]. Indeed, NHC-metal complexes have
been proved to be more effective in many catalytic reactions than
phosphineemetal complexes [24e26]. Recently, NHC-Pd complexes
have been reported to catalyze a wide variety of useful cross-
coupling reactions [27e36]. To date, the development of green
chemistry throughorganic reactions conducted inwaterhas become
one of the most exciting research endeavors in organic synthesis
[37e40]. Nevertheless, only a few examples of SuzukieMiyaura,
MizorokieHeck, and Sonogashira reactions by using water as the
solvent are reported in the literature [7,37,41e53]. Furthermore, to
the best of our knowledge, no report in the literature describing on
bis-NHC-Pd catalyst derived from caffeine for running Suzukie
Miyaura, MizorokieHeck, and Sonogashira reactions in water
to date. Herein, we report on the short and simple synthesis of
the clear solution to obtain
a yellow precipitate. Filtration,
concentration, and recrystallization from ethyl acetate could give
1,3,7,9-tetramethylxanthinium iodide as a yellowish white solid in
78% yield [54]. TOF MS ES þ showed 1,3,7,9-tetramethylxanthinium
cation at m/z 209 (C9H13N4O2) and bis(1,3,7,9-tetramethylxanthi-
nium) iodide cation at m/z 545 (C18H26IN8O4), while TOF MS
ESꢁ showed 1,3,7,9-tetramethylxanthinium diiodide anion at m/z
463 (C9H13I2N4O2). The following reaction of 1,3,7,9-tetramethyl-
xanthinium iodide with sodium tert-butoxide in the presence of
Pd(OAc)2 in dry THF could give bis(1,3,7,9-tetramethylxanthine-
8-ylidene)palladium diiodide (1) as a white powder in 83% yield
after recrystallization from methanol. While its 1H NMR spectrum
running at 500 MHz in CDCl3 showed two sets of signals with
a ratio about 1 to 1, its 13C NMR spectrum running at 125 MHz in
CDCl3 showed only one set of signals at room temperature.
However, two sets of signals with a ratio about 1 to 1 assignable
to the probable syn and anti diastereomers of 1 were shown in
its 13C NMR spectra running at 125 MHz in CDCl3 at ꢁ30 ꢀC.
* Corresponding author. Tel.: þ886 2 27898576; fax: þ886 2 27888199.
E-mail address: luoft@chem.sinica.edu.tw (F.-T. Luo).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.11.002

F.-T. Luo, H.-K. Lo / Journal of Organometallic Chemistry 696 (2011) 1262e1265
1263
tert-BuONa
Pd(OAc)2
O
O
O
Me
N
Me
N
Me
N
Me
O
Me
O
Me
O
MeI
N
N
N
PdI2
I
THF, 70 oC, 3 h
2
N
Me
N
N
Me
DMF
N
Me
N
Me
N
Me
1
Scheme 1. Synthesis of bis-NHC-Pd complexes 1 from caffeine.
Table 1
Table 3
SuzukieMiyaura coupling reaction using bis-NHC-Pd catalyst 1.
MizorokieHeck Reaction using bis-NHC-PdI2 catalyst 1.
2 mol % Pd cat.
OMe
2 mol % Pd cat. 1
Z
O
+
X
Z
+
X
(HO)2B
base, 90 °C
O
base, H2O, 6 h
OMe
Z = H, MeCO-
X = Br, I
Me
X = Br or I
Me
Entry Haloarene
Solvent
Base
KOH
K2CO3 12
KOH 12
Time (h) Iso. Yield (%)
Entry
Haloarene
Base
Temp (ꢀC)
Iso. Yield (%)
1
2
3
4
5
6
4-Bromoacetophenone H2O
4-Bromoacetophenone H2O
4-Bromoacetophenone H2Oa
4-Bromoacetophenone H2Oa
Iodobenzene
Iodobenzene
12
51%
52%
87%
92%
92%
90%
1
2
3
4
4-Bromotoluene
4-Bromotoluene
4-Bromotoluene
3-Bromotoluene
KOH
NaO-t-Bu
KOH
65
25
25
65
95%
88%
<30%
91%
K2CO3 12
KOH
H2O/DMAb Et3N
H2O
6
6
Et3N
a
EIeMS showed signals at m/z 776 (C18H24I2N8O4Pd, Mþ), 649
(C18H24IN8O4Pd), 568 (C9H12I2N4O2Pd), 522 (C18H24N8O4Pd), 441
(C9H12IN4O2Pd), and 314 (C9H12N4O2Pd).
The volume ratio for water:Brij 30 ¼ 2:1.
The volume ratio for H2O/DMA ¼ 1:1.
b
good yields at 90 ꢀC (entries 4 and 6). Adding more Brij 30 could not
further improve the yield when sodium t-butoxide was used as the
base (entry 8). However, adding more Brij 30 could greatly improve
the yield when potassium hydroxide was used as the base at 90 ꢀC
(entries 3, 5, and 7). The results of Heck reaction for 4-bromoace-
tophenone or iodobenzene and methyl acrylate (5 equiv) in the
presence of 2 mol % of catalyst 1 under various conditions was
proceeded as the model reaction as shown in Table 3. We observed
that the presence of Brij 30 could greatly improve the yield when
potassium hydroxide or potassium carbonate was used as the base
at 90 ꢀC (entries 1e4). When we used triethylamine as the base and
either water or aqueous DMA as the solvent to run the Heck reac-
tion, we could obtain the desired product in more than 90% isolated
yields (entries 5 and 6).
To test the applicability of bis-NHC-Pd catalyst 1, we examined
the Suzuki reaction of p- or m-bromotoluene and phenylboronic
acid and various bases in the absence or presence of 1 in water as
shown in Table 1. It was noted that in the absence of bis-NHC-Pd
catalyst 1, there was no detectable amount of the desired coupled
product formed as judged by the GCeMS analysis. The reaction is
preferred to run at higher temperature in water when potassium
hydroxide was used as the base (entries 1, 3, and 4). Probably, the
solubility of the catalyst was increased at higher temperature.
However, when sodium t-butoxide was used as the base, the cross-
coupling reaction using 1 as the catalyst could give good yields in
water at room temperature (entry 2). The applicability of 1 as the
catalyst in Sonogashira reaction was run for p-bromonitrobenzene
and phenylacetylene under various conditions as shown in Table 2.
In the absence of the catalyst, there was no detectable amount of
the desired product formed as judged by 1H NMR and GCeMS
analysis. The reaction could not proceed very well in water even at
90 ꢀC (entries 1 and 2). Adding 1 equivalent of Brij 30 [55] as the
nonionic surfactant in the reaction mixture and sodium t-butoxide
as the base could improve its low yield at room temperature to
3. Conclusions
In conclusion, we have demonstrated the synthesis of a new
bis-NHC-PdI2 catalyst
1 which was successfully employed in
the carbonecarbon bond formation to give good yields in the
Table 2
Sonogashira reaction using bis-NHC-PdI2 catalyst 1.
2 mol % Pd cat.
CuI, base, 24 h
+
Br
O2N
O2N
Entry
Solvent
Base
Temp (ꢀC)
Iso. Yield (%)
1
2
3
4
5
6
7
8
H2O
H2O
KOH
NaOet-Bu
KOH
NaOet-Bu
KOH
NaOet-Bu
KOH
90
90
25
25
90
90
90
90
<5%
<5%
21%
22%
43%
81%
96%
83%
H2Oa
H2Oa
H2Oa
H2Oa
H2Ob
H2Ob
NaOet-Bu
a
Containing 1 equivalent of Brij 30 as the nonionic surfactant.
The volume ratio for water:Brij 30 ¼ 2:1.
b

1264
F.-T. Luo, H.-K. Lo / Journal of Organometallic Chemistry 696 (2011) 1262e1265
MizorokieHeck, SuzukieMiyaura, and Sonogashira model studies in
aqueous solution. In addition to its good reactivity in aqueous solu-
tion, caffeine is found in many plant species. Thus, its short and
simplicity, good yields, readily available from natural sources such as
coffee and tea in its preparation gave us a promising solution toward
green chemistry.
identified by comparison their 1H NMR and MS spectral data as
reported in the literature.
4.4. General procedure for Sonogashira reaction
A solution of p-bromonitrobenzene (5 mmol) and phenyl-
acetylene (5.5 mmol) in water (20 mL) with pertinent amount of
Brij 30 was added to the mixture of copper iodide (0.1 mmol), bis-
NHC-PdI2 catalyst 1 (0.1 mmol) and base (18 mmol). The reaction
was heated at 90 ꢀC for 24 h. The organic layer was extracted with
diethyl ether, dried over magnesium sulfate, and the solvent was
removed completely under high vacuum to give a crude product.
The pure product was purified by column chromatography on silica
gel (neutral, 70e230 mesh, n-hexane: ethyl acetate ¼ 10:1). The
product was identified by comparison the 1H NMR and MS spectral
data as reported in the literature.
4. Experimental section
4.1. Synthesis of 1,3,7,9-tetramethylxanthinium iodide
Caffeine (4.50 g, 23.2 mmol) in dry N,N-dimethylformamide
(50 mL) was heated to 100 ꢀC and then added methyl iodide (7.2 mL,
116 mmol) and stirred at 100 ꢀC for 20 h. An excess amount of ethyl
acetate (150 mL) was added to the clear solution to obtain a yellow
precipitate. Filtration and washing with ethyl acetate three times
could afford a pale yellow powder. Recrystallization from ethyl
acetate gave the desired product as a yellowish white solid (6.04 g,
18.2 mmol, 78% yield). Mp: 179e180 ꢀC. Anal. Calc. for C9H13IN4O2: C,
32.16; H, 3.90; N, 16.67; Found: C, 32.00; H, 3.98; N, 16.47. 1H NMR
4.5. General procedure for MizorokieHeck reaction
A mixture of iodobenzene (5 mmol), methyl acrylate (25 mmol),
triethylamine (15 mmol), and 2 mol % of bis-NHC-PdI2 catalyst 1 in
10 mL of a mixture of water and DMA (the volume ratio for
H2O/DMA ¼ 1:1) were stirred at 90 ꢀC for 6 h under nitrogen. The
organic layer was extracted with diethyl ether, dried over magne-
sium sulfate, and the solvent was removed completely under high
vacuum to give a crude product. The pure product was further
purified by column chromatography on silica gel (neutral, 70e230
mesh, n-hexane: ethyl acetate ¼ 10:1). The products were identi-
fied by comparison their 1H NMR and MS spectroscopic data as
reported in the literature.
(400 MHz, DMSO-D6):
d
3.27 (s, 3H), 3.74 (s, 3H), 4.05 (s, 3H), 4.15
28.38,
(s, 3H), 9.31 (s, 1H) ppm. 13C NMR (100 MHz, DMSO-D6):
d
31.36, 35.61, 36.88,107.74,139.26,139.57,150.16,153.28ppm. TOFMS
ESþ (m/z): 209 (C9H13N4O2), 545 (C18H26IN8O4). TOF MS ESꢁ (m/z):
463 (C9H13I2N4O2). TOF HRMS ES þ calcd for C9H13N4O2 209.1033,
found 209.1040. TOF HRMS ES þ calcd for C18H26N8O4I 545.1122,
found 545.1117. TOF HRMS ESꢁ calcd forC9H13N4O2I2 462.9128, found
462.9130.
4.2. Synthesis of bis(1,3,7,9-tetramethylxanthine-8-ylidene)
palladium diiodide
Acknowledgements
To a mixture of 1,3,7,9-tetramethylxanthinium iodide (0.61 g,
1.8 mmol), Pd(OAc)2 (0.20 g, 0.9 mmol) and NaO-t-Bu (0.17 g,
1.8 mmol) was added dry THF (20 mL) under nitrogen atmosphere
and stirred for 1.5 h at room temperature first and then refluxed for
3 h. After cooling to the room temperature, the reaction mixture was
slowly added to hexane (60 mL) to get a yellow precipitate. Filtration,
concentration, and recrystallization from methanol to give a white
powder (0.58 g, 0.75 mmol) in 83% yield. Mp: >300 ꢀC. Anal. Calc. for
C18H24O4N8PdI2 (776.66): C, 27.84; H, 3.11; N, 14.43. Found: C, 27.58;
The authors thank the National Science Council of ROC and
Academia Sinica for their kindly financial support.
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