Application of 3-aroyl-4(5)-arylimidazols as efficient ligands in Pd-catalyzed Heck reactions

Article abstract of DOI:10.3906/kim-1307-18

The Heck coupling of haloarenes with various alkenes was successfully performed in the presence of 0.25 mol% PdCl₂ and 0.5 mol% biphenyl-4-yl-[4(5)-(biphenyl-4-yl)-1 H-imidazol-2-yl]ketone 2f as a ligand with Na₂ CO₃ as optimal base, in a 1:1 mixture of H ₂ O/DMF as the reaction solvent at 80 °C for 8 h. Imidazole 2f was found to be an inexpensive, air-stable, easily available, and efficient ligand in the palladium-catalyzed Heck reactions of aryl iodides (76%-94%), bromides (52%-79%), and chlorides (40%-70%). TUBITAK.

Full text of DOI:10.3906/kim-1307-18

Turk J Chem
Turkish Journal of Chemistry
(2014) 38: 547 – 552
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http://journals.tubitak.gov.tr/chem/
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⃝ TUBITAK
doi:10.3906/kim-1307-18
Research Article
Application of 3-aroyl-4(5)-arylimidazols as efficient ligands in Pd-catalyzed Heck
reactions
Mojtaba AMINI1,∗, Seyedeh Motahhareh AMINI2, Bagher EFTEKHARI-SIS1,∗
Ali KEIVANLOO2
1Department of Chemistry, Faculty of Science, University of Maragheh, Maragheh, Iran
2School of Chemistry, Shahrood University of Technology, Shahrood, Iran
,
Received: 08.07.2013
•
Accepted: 03.12.2013
•
Published Online: 11.06.2014
•
Printed: 10.07.2014
Abstract: The Heck coupling of haloarenes with various alkenes was successfully performed in the presence of 0.25
mol% PdCl2 and 0.5 mol% biphenyl-4-yl-[4(5)-(biphenyl-4-yl)-1H -imidazol-2-yl]ketone 2f as a ligand with Na2 CO3 as
optimal base, in a 1:1 mixture of H2 O/DMF as the reaction solvent at 80 ◦ C for 8 h. Imidazole 2f was found to be
an inexpensive, air-stable, easily available, and efficient ligand in the palladium-catalyzed Heck reactions of aryl iodides
(76%–94%), bromides (52%–79%), and chlorides (40%–70%).
Key words: Aroylimidazoles, PdCl2 , Heck reaction, aqueous medium
1. Introduction
Imidazoles moieties are broadly found in natural products such as biotin, histidine, histamine, and the pi-
locarpine alkaloids,1,2 and also are present in important synthetic compounds such as losartan, fungicides,
herbicides, and therapeutic agents.3,4 Furthermore, recently, imidazoles have been found as a skeleton of ionic
liquids and efficient ligands in metalloenzymes and metal complexes.5 Therefore, there are many reports in the
literature on the synthesis of imidazole derivatives.6,7
The Mizoroki–Heck reaction,8−11 palladium-catalyzed olefination of aryl halides, has become one of the
most powerful methods for carbon–carbon bond formation in organic synthesis.12−15 Phosphine ligands are
commonly used in the Heck reaction but suffer from some disadvantageous such as environmental problems,
moisture and air sensitivity, high toxicity, and cost of phosphine ligands.16−18 Therefore, the development
of new phosphine-free catalytic systems for the Heck reaction would be an interesting subject, among which
imidazoles play an important role.19,20 In continuation of our work on the Heck reaction,21,22 recently we have
reported the Heck reaction using a Pd(OAc)2 /imidazolium salt catalytic system, which afforded corresponding
Heck products in good to excellent yields.23 The results encouraged us to work on the Heck reaction using
easily prepared and air and moisture stable aroylimidazole-based ligands 2.
2. Results and discussion
Different substituted aroylimidazoles 2 were prepared by reaction of arylglyoxal hydrate 1 with ammonium
acetate in water at room temperature as Khalili et al. reported (Scheme),7 and then subjected to the Heck
∗Correspondence: mamini@maragheh.ac.ir; eftekhari.sis@gmail.com
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AMINI et al./Turk J Chem
reaction of styrene with iodobenzene, as a ligand in the presence of PdCl2 in DMF at 80 ◦ C for 8 h. The
results are summarized in Table 1. Electron-donating and electron-withdrawing substituted aroylimidazoles 2
were investigated as ligand in the Heck reaction, and, due to the best results, biphenyl-4-yl-[4(5)-(biphenyl-4-
yl)-1H -imidazol-2-yl]ketone 2f (Table 1, entry 6) was selected for further reactions. For investigation of ligand
effect on the Heck reaction, we carried out the Heck reaction between styrene and iodobenzene under similar
conditions without using any ligand, which afforded the trans-stilbene in only 37% yield (Table 1, entry 7).
Scheme. Synthesized aroylimidazole ligands 2a–f.
Table 1. The effect of ligands 2a–f on the Heck reaction.
Yield %
GC Isolated
Entry
Ligand 2; R
Trans/cisa
1
2
3
4
5
6
7
2a; H
75
73
82
85
65
62
69
73
78
85
-
91/9
94/6
94/6
94/6
93/7
91/9
> 99/1
2b; 4-NO2
2c; 3-MeO
2d; 4-MeO
2e; 3,4-(MeO)2 86
2f; 4-Ph
None
97
37
aDetermined by GC.
Different solvents were used in the Heck reaction of 0.6 mmol styrene with 0.5 mmol iodobenzene in the
presence of 0.5 mol% ligand 2f, 0.25 mol% of PdCl2 , and 1 mmol K2 CO3 . The reactions were carried out at
80 ◦ C for 8 h. The results are summarized in Table 2, which shows that EtOH, EtOH/water (50/50: v/v),
t-BuOH, t-BuOH/water (50/50: v/v), and toluene (entries 6–10) afforded stilbene in very low yield. When
DMSO or DMSO/water was used as reaction medium, stilbene was obtained in 66% or 80% yield, respectively,
with low selectivity (trans/cis = 50/50–60/40). Reaction in DMF afforded the product in 80% isolated yield
with a trans/cis ratio of 94/6. When the reaction was conducted in DMF/water (50/50: v/v), stilbene was
isolated in 88% yield, with a 91/9 ratio of trans/cis. Interestingly, in water (entry 5), cis-stilbene was the
major product. Due to high yield and selectivity and environmental acceptability, the 50/50 (v/v) mixture of
DMF/water was selected as the best reaction solvent for the Heck reaction.
As illustrated in Table 3, also, different bases were examined in the Heck reaction between 0.6 mmol
styrene and 0.5 mmol iodobenzene in the presence of 0.25 mol% PdCl2 and 0.5 mol% ligand 2f in DMF/water
(50/50: v/v) at 80 ◦ C. In the case of Na3 PO4 , the reaction did not occur after 8 h. However, NaOAc and
Et3 N afforded the product with excellent trans-selectivity, but the yields were very low, in both cases. When
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AMINI et al./Turk J Chem
Na2 CO3 and K2 CO3 were used, stilbene was obtained in 92% and 88% yields with 94/6 and 91/9 trans/cis
selectivity, respectively. Therefore, Na2 CO3 was selected as the optimum base for further Heck reactions.
Table 2. The effect of solvent on the Heck reaction.a
Yield %
Entry
Solvent
Trans/cisb
GC
97
79
Isolated
80
66
1
2
3
4
5
6
7
8
9
10
DMF
DMSO
94/6
60/40
91/9
50/50
17/83
−
DMF/water (50/50: v/v) 100 88
DMSO/water (50/50: v/v)
water
EtOH
t-BuOH
EtOH/water (50/50: v/v)
t-BuOH/water (50/50: v/v)
Toluene
99
52
80
20
NRc NRc
−
11
10
−
−
−
NRc NRc
NRc NRc
−
−
a Reaction conditions: Styrene (0.6 mmol), iodobenzene (0.5 mmol), PdCl2 (0.25 mol%), Ligand 2f (0.5 mol%), K2 CO3
c
(1 mmol), 80 ◦ C, 8 h. b Determined by GC. No reaction.
Table 3. The effect of bases on the Heck reaction.a
Yield %
Entry
Base
Trans/cisb
GC
98
Isolated
88
1
2
3
4
5
K2CO3
91/9
94/6
100/0
100/0
-
Na2CO3 100 92
NaOAc
Et3N
Na3PO4
21
13
NRc
16
10
a Reaction condition: styrene (0.6 mmol), iodobenzene (0.5 mmol), PdCl2 (0.25 mol%), ligand 2f (0.5 mol%), DMF/water
(50/50: v/v; 2 mL), 80 ◦ C, 8 h. b Determined by GC. c No reaction.
To broaden the catalytic applicability of the ligand 2f, we subsequently examined Heck coupling reactions
of arylhalides with various olefins (Table 4). The results indicated that the combination of PdCl2 and 2f was
efficient for the Heck coupling reaction of a series of alkenes and aryl halides (Table 4). The reaction of aryl
iodides and bromides with olefins occurred easily and the desired products were obtained in good yields (Table 4,
entries 1–12). As expected, the catalytic activity depended on the halide, while electron-withdrawing groups on
the aryl ring increased the reaction rate and this general trend was observed for both aryl bromides and chlorides.
However, the Heck coupling of chlorobenzene was difficult to achieve under the same reaction conditions and
low amounts of coupling product were observed (Table 4, entries 13–19). In general, coupling of aryl iodides and
bromides with olefins was found to give products in good to excellent yields (52%–97%). The reduced yields of
chlorobenzenes are mostly a consequence of the nonreactive nature of these substrates.
It is clear that ligands with coordination to palladium during the catalytic process of the Heck reaction
could improve the stability of palladium complexes and therefore the catalytic activity induced by ligands
is indeed better than under ligandless conditions.24 To study the coordination of ligand 2f to palladium
and complex formation during the catalytic process, IR and the electronic spectra of ligand and complex
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AMINI et al./Turk J Chem
PdCl2 /ligand 2f were recorded. The C=O stretching frequencies for the ligand occur at 1619 cm−1 and for the
complex it is expected to appear at lower frequencies (1602 cm−1) when compared to the ligand. This shift by
at least 17 cm−1 to a lower frequency compared to that of the free ligand indicates a decrease in the bond order
due to the coordinate bond of the palladium with the oxygen lone pair of ligand. Moreover, the signal appearing
at 3274 cm−1 , due to the imidazole NH group, disappears in the spectra of the complex, demonstrating that the
coordination of ligand was performed. The coordinating modes of the ligand 2f were confirmed by comparing
the electronic spectra of ligand and complex in DMSO solution (Figure). It was found that, in complex, the
band at 360 nm of ligand slightly shifted to longer wavelength along with decreases in its intensity. Conversely,
the new band at λmax = 465 nm was observed in complex. On the basis of spectral results, one could assume
the formation of new species of type Pd-ligand 2f as a catalytic complex involved in the reaction.
Table 4. Heck reaction between aryl halides and olefins.a
Entry
1
2
3
4
X
I
I
I
I
R’
H
H
H
H
H
R”
Ph
Yield %b
85
COn2 Bu 84
CO2Me 76
CO2Et 80
5
6
I
COMe
94
63
Br 4-MeCO Ph
7
8
9
Br 4-MeCO COn2 Bu 57
Br 4-MeCO CO2Et 64
Br 4-MeCO CO2Me 52
10
11
12
13
14
15
16
17
18
19
Br 4-MeCO COMe
75
Br
Br
H
H
COn2 Bu 79c
Ph
58c
45
Cl 4-MeCO Ph
Cl 4-MeCO COn2 Bu 40
Cl 4-MeCO CO2Et 55
Cl 4-MeCO CO2Me 40
Cl 4-MeCO COMe
70
50c
Cl
Cl
H
H
Ph
COn2 Bu 40c
a Reaction conditions: 0.5 mmol of aryl halide, 0.6 mmol of olefins, 1 mmol of Na2 CO3 , 0.25 mol% PdCl2 , 0.5 mol%
2f, 80 ◦ C, 2 mL (1:1) mixture of H2 O/DMF as solvent. b Isolated yield. c 24 h.
3. Experimental section
All the reactions were carried out under air. Chemicals and solvents were purchased from the Fluka and Merck
Chemical companies and used without purification. The reaction products of the Heck reaction were determined
and analyzed by a HP Agilent 6890 gas chromatograph equipped with a HP-5 capillary column (phenyl methyl
siloxane 30 m × 320 µm × 0.25 µm) and a flame-ionization detector. All products were isolated by short
column chromatography on silica gel 60 (0.063–0.20 mesh ASTM) using hexane/ethyl acetate as eluent.
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AMINI et al./Turk J Chem
Figure. UV-Vis spectra of ligand 2f and complex.
In order to show the merit and efficiency of the present catalytic complex, the Heck coupling reaction
between iodobenzene and styrene under the same reaction conditions was studied. It was found that complex
promoted the Heck coupling reaction, giving excellent conversion (100%) and high selectivity (93%) to trans-
stilbene.
3.1. Synthesis of ligands 2
To a mixture of an arylglyoxal hydrate (1 mmol) in water (5 mL) was added NH4 OAc (5 mmol) at room
temperature and stirred at the same temperature for 1 h. Then the reaction mixture was solidified and the
obtained solid was filtrated, washed with water (3–15 mL), and the crude product was purified by crystallization
from ethanol.7
3.2. Synthesis of PdCl2 -ligands 2f complex
A mixture of ligand 2f (0.07 mmol) and PdCl2 (0.035 mmol) in 4 mL of DMF/water (1/1; v/v) was heated at
100 ◦ C for 1.5 h. Then the obtained solid was filtered and washed with water.
3.3. General procedure for the Heck reactions
All Heck reactions were carried out under air. A mixture of aryl halide (0.5 mmol), olefins (0.6 mmol), Na2 CO3
(1 mmol), PdCl2 (0.25 mol%), and ligand 2f (0.5 mol%) in a 1/1 (v/v) mixture of H2 O/DMF (2 mL) was
allowed to react in a sealed tube at 80 ◦ C. The reaction mixtures were added to brine (15 mL) and extracted 3
times with diethyl ether (3 × 15 mL). The combined organic phase was analyzed by GC. The further purification
of the product was achieved by flash column chromatography on silica gel using hexane/ethyl acetate (5:1).
In summary, we have developed an efficient phosphine-free Heck reaction using aroylimidazoles as ligand
in aqueous DMF. Easy preparation of aroylimidazoles ligands and high yields of the Heck products with high
trans-selectivity using a cheap and available base (Na2 CO3) are some advantageous of it.
Acknowledgment
The authors thank the Research Council of University of Maragheh for its support of this work.
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AMINI et al./Turk J Chem
References
1. Ho, J. Z.; Hohareb, R. M.; Ahn, J. H.; Sim, T. B.; Rapoport, H. J. Org. Chem. 2003, 68, 109–114.
2. Faulkner, D. J. Nat. Prod. Rep. 2000, 17, 7–55.
3. Lombardino, J. G.; Wiseman, E. H. J. Med. Chem. 1974, 17, 1182–1188.
4. Lo, Y. S.; Nolan, J. C.; Maren, T. H.; Welstead, Jr., W. J.; Gripshover, D. F.; Shamblee, D. A. J. Med. Chem.
1992, 35, 4790–4794.
5. Vallee, B. L.; Auld, D. S. Biochemistry 1990, 29, 5647–5659.
6. Eftekhari-Sis, B.; Zirak, M.; Akbari, A. Chem. Rev. 2013, 113, 2958–3043; and references cited therein.
7. Khalili, B.; Tondro, T.; Hashemi, M. M. Tetrahedron 2009, 65, 6882–6887; and referenced cited therein.
8. Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn. 1971, 44, 581–581.
9. Heck, R. F.; Nolley, Jr., J. P. J. Org. Chem. 1972, 37, 2320–2322.
10. Dieck, H. A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96, 1133–1136.
11. Dieck, H. A.; Heck, R. F. J. Org. Chem. 1975, 40, 1083–1090.
12. Bras, J. L.; Muzart, J. Chem. Rev. 2011, 111, 1170–1214.
13. Dounay, A. B.; Overman, L. F. Chem. Rev. 2003, 103, 2945–2964.
14. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009–3066.
15. Trzeciak, A. M.; Zi´o lkowski, J. J. Coord. Chem. Rev. 2005, 249, 2308–2322.
16. Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10–11.
17. Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989–7000.
18. Zapf, A.; Beller, M. Chem. Eur. J. 2001, 13, 2908–2915.
19. Haneda, S.; Ueba, C.; Eda, K.; Hayashi, M. Adv. Synth. Catal. 2007, 349, 833–835.
20. Haneda, S.; Okui, A.; Ueba, C.; Hayashi, M. Tetrahedron 2007, 63, 2414–2417.
21. Bagherzadeh, M.; Amini, M.; Ellern, A.; Woo, L. K. Inorg. Chim. Acta 2012, 383, 46–51.
22. Amini, M.; Bagherzadeh, M.; Moradi-Shoeilib, Z.; Boghaei, D. M. RSC Advances 2012, 2, 12091–12095.
23. Amini, M.; Bagherzadeh, M.; Rostamnia, S. Chinese Chem. Lett. 2013, 24, 433–436.
24. Qadir, M.; M¨ochel, T.; Hii, K. K. Tetrahedron 2000, 56, 7975–7979.
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