CuCl2/[hmim]Br: A new recyclable catalytic system for aromatization of cyclic dienes

Article abstract of DOI:10.1016/j.catcom.2017.10.009

The combination of copper(II) chloride and 1-hexyl-3-methylimidazolium bromide ([hmim]Br) as a new recyclable catalytic system in the presence of TBHP for aromatization of cyclic dienes is disclosed. The system could furnish the corresponding aromatics in moderate to excellent yield. The competition between aromatization and oxidation of benzylic substrates were also studied. This developed catalytic system could be reused and recycled at least nine times without significant loss of the producitivity.

Full text of DOI:10.1016/j.catcom.2017.10.009

Accepted Manuscript
CuCl2/[hmim]Br: A new recyclable catalytic system for
aromatization of cyclic dienes
Piyada Taboonpong, Warinthorn Chavasiri
PII:
DOI:
Reference:
S1566-7367(17)30420-X
doi:10.1016/j.catcom.2017.10.009
CATCOM 5220
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
11 September 2017
2 October 2017
5 October 2017
Please cite this article as: Piyada Taboonpong, Warinthorn Chavasiri , CuCl2/[hmim]Br:
A new recyclable catalytic system for aromatization of cyclic dienes. The address for
the corresponding author was captured as affiliation for all authors. Please check if
appropriate. Catcom(2017), doi:10.1016/j.catcom.2017.10.009
This is a PDF file of an unedited manuscript that has been accepted for publication. As
a service to our customers we are providing this early version of the manuscript. The
manuscript will undergo copyediting, typesetting, and review of the resulting proof before
it is published in its final form. Please note that during the production process errors may
be discovered which could affect the content, and all legal disclaimers that apply to the
journal pertain.

ACCEPTED MANUSCRIPT
Catalysis Communications
CuCl2/[hmim]Br:A new recyclablecatalyticsystemforaromatization of cyclicdienes
Piyada Taboonpong, Warinthorn Chavasiri*
Center of Excellence in Natural Products Chemistry, Department of Chemistry,
Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
*Corresponding author. Tel.: +66 2 2187625; fax: +66 2 2187598 (W.C.);
e-mail: warinthorn.c@chula.ac.th
Abstract
The combination of copper(II) chloride and 1-hexyl-3-methylimidazolium bromide ([hmim]Br)
as a new recyclable catalytic system in the presence of TBHP for aromatization of cyclic dienes
is disclosed. The system could furnish the corresponding aromatics in moderate to excellent
yield. The competition between aromatization and oxidation of benzylic substrates were also
studied. This developed catalytic system could be reused and recycled at least nine times without
significant loss of the producitivity.
Keywords: Copper(II) chloride; Ionic liquid; Aromatization; Dienes
1. Introduction
Aromatization is one of dehydrogenations utilizing for hydrogen molecule removal.
Numerous reports for aromatization of polycyclic hydroaromatics employing various catalysts
and reagents such as single metal, metal complexes, quinones, and oxidizing agents have been
reported [1]. Single metal and metal complexes mostly reacted under high temperature and
required long reaction time which are not suitable to apply to other easily sensitive substrates.
Later, some reports on aromatization with metal salts using alkenes instead of polycylic
hydrocarbons to synthesize aromatics such as titanium salt [2], iron salt [3], iron complexes [4],
tin or antimony salts [5], and copper salts [6] were addressed.

ACCEPTED MANUSCRIPT
Catalysis Communications
Recently, the system comprising of tert-butyl hydroperoxide (TBHP) combining with
copper salt was developed for aromatization of cyclic dienes [7]. Conjugated and skipped dienes
were studied. The Cu-TBHP system provided the desired product in high yield under mild
conditions with short reaction time; however, the reaction required MeCN as a media [8]. Due to
the solubility of Cu salts that cannot be reused after working-up process, the present new and
efficient system is developed using ionic liquids (ILs) so that aromatic compounds can be
synthesized under a new recyclable catalytic system. In the past several years, several reports
about ionic liquids have been addressed; mainly described about oxidation [9-11]. The use of
H2O2 as a terminal oxidant in ILs has received great attention; however, the reagent mostly
worked well in metal catalyst systems [12]. Therefore, in order to avoid using those metal
complexes which may have toxicity or complicated preparation process, there have been
developed for oxidation in the ILs by using TBHP instead.
Even though, there have been many reviews of the use of TBHP for oxidation [13, 14],
there are never been reported on aromatization of cyclic dienes in ILs, especially in 1-hexyl-3-
methylimidazolium bromide ([hmim]Br). Herein, we disclose the aromatization using Cu
salt/[hmim]Br in the presence of TBHP as a new catalytic system which allow the possibility of
recycling of homogeneous catalysts.
2. Experimental
In a typical procedure for aromatization of cyclic dienes, a selected cyclic diene (1.0
mmol) and 3.0 or 6.0 equiv of TBHP (70% in water) were added to a round-bottom flask
containing [hmim]Br (1.0 g) and 5 mol% CuCl2 (6.7 mg). After stirring at room temperature
(28oC) for 15 min, the reaction mixture was extracted from ionic liquid phase with diethyl ether
(10.0 mL x 3). The organic layer was washed with distilled water, dried over anhydrous NaSO4
and then quantified the product yield by GC with naphthalene or biphenyl as the internal
standard. For recycle and reuse, the ionic-liquid residue was evaporated in the rotary evaporator
at
50oC
for
2 h.
3. Results and discussion

ACCEPTED MANUSCRIPT
Catalysis Communications
-Terpinene as a model compound of skipped diene was investigated with various
parameters such as solvent, external oxidant, reaction time and amount of selected oxidant to
obtain appropriate optimum conditions for the aromatization.
Four solvent systems (Table 1): MeCN, 1-butyl-3-methylimidazolium bromide
([bmim]Br), [hmim]Br and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) were
tested under similar conditions to the previous report [7]. The screening results showed that
MeCN was the best (Table 1, entry 1). Due to the above mentioned problems, three ILs were
considered. Even though those ILs showed similar results (Table 1, entries 2-4), [hmim]Br was
the most interesting. Owing to copper salt solubility in the solvent system, the catalyst could be
soluble in [hmim]Br as in MeCN. Moreover, many reports supported that in the presence of
TBHP good productivity of oxidation reaction with [hmim]Br could be attained.
Table 1. Screening ofsolvent systemsa
Recovered
substrate
(% )
Yield
(% )
MB
(% )
Entry
Solvent
1
2
MeCN
quant.
37
-
quant.
97
60
3
32
45
65
54
97
99
4b
a Condition: -terpinene (1 mmol), TBHP (in water),
solvent (1 mL or g), RT (28oC), GC yield with naphthalene as
the internal standard
b The catalyst did not dissolve.
The reaction was carried out with various reaction times: 15, 30 min, 1, and 3 h in order
to improve the product yield. Even though 15 min was not enough to complete the reaction, the
yield could be higher by adjusting other parameters. The amount of TBHP was also varied to

ACCEPTED MANUSCRIPT
Catalysis Communications
search for the suitable ratio so that the reaction could reach the maximum yield. The
investigation of the amount of TBHP is shown in Figure 1.
TBHP (eq)
6.0
4.5
3.0
1.5
0.0
99
99
91
32
40
3
0
20
60
80
100
Yield (%)
Figure 1. The effects ofthe amount ofTBHP.
Condition:-terpinene (1mmol), TBHP (70% in water),
[hmim]Br, RT (28 oC), 15 min, GC yield
Treating the reaction with 4.5 equivalents based on the starting material was enough to
complete. In addition, the product yield did not increase after treating the reaction with higher
equivalent of TBHP (6.0 eq) while it almost showed no reaction without using the oxidant.
TBHP was needed and 6.0 equivalents would be used for the optimum so that the reaction could
complete within shorter reaction time.
The optimum condition was used to extend the scope of the procedure; this catalytic
system was investigated with other cyclic substrates (Table 2).
Table 2. Aromatization ofselected substratesa

ACCEPTED MANUSCRIPT
Catalysis Communications
Yield
(% )b
Entry
Substrate
Product
1
99
14
2
3
4
(72)c
47
55
a All conditions were carried out with substrate (1 mmol), under
optimized conditions for -terpinene
b GC yield with naphthalene or biphenyl as the internal standard
c Anthraquinone
Unlike -terpinene, the conjugated dienes as -terpinene and 1,2-dihydronaphthalene
(Table 2, entries 3-4) provided moderate yield (40–60% yield) under this developed protocol.
Referring to previous studies of Cu-TBHP systems [7, 15-18], the mechanism for aromatization
of -terpinene was proposed in Scheme 1. Those generated radical active species from copper
ion-TBHP interaction rapidly reacted with C-H bond at allylic position of the substrate and
generated intermediates prior to aromatization.

ACCEPTED MANUSCRIPT
Catalysis Communications
Scheme 1. The proposed mechanismforaromatization of
-terpinene catalyzed Cu-TBHPsystem
According to previous reports concerning the C-H bond strengths of conjugated and
skipped dienes (1,3-cyclohexadiene and 1,4-cyclohexadiene) [19], skipped dienes with less C-H
bonds strength provided more stable intermediate while that generated from conjugated dienes
was unstable and quite active. This should be a reason why conjugated dienes were transformed
into their final products in lower yield than skipped ones. In case of 9,10-dihydroanthracene, the
expected product was found in low yield together with the occurrence of the other product,
anthraquinone (Table 2, entry 2).
Even though the aromatization of 9,10-dihydroanthracene (Table 2, entry 2) took place
with 100% conversion, it generated not only the aromatic product but also diketone. Therefore,
the reaction of 9,10-dihydroanthracene was further investigated by adjusting some parameters
including reaction time, reaction temperature, and amount of the oxidant to look for selective
reaction conditions.
Longer reaction time and higher temperature were not two essential parameters to convert
the starting material into a single desired product. When the reaction was nevertheless treated

ACCEPTED MANUSCRIPT
Catalysis Communications
with higher concentration of TBHP, anthraquinone was produced as the sole product under both
higher and longer reaction.
The reaction of 9,10-dihydroanthracene did not give the expected aromatized compound,
it generated anthraquinone instead. So, this catalytic system showed a competitive reaction
between aromatization and oxidation of benzylic compound (Figure 2).
Figure 2. Competitive reactionsof9,10-dihydroanthracene
Other independent experiments were conducted trying to explain this competition. Under
the developed conditions, anthracene was converted into anthraquinone with 54% yield. While
diphenylmethane produced the corresponding ketone in low yield (16%). Thus, it could be
assumed that anthraquinone being generated from aromatization of 9,10-dihydroanthracene to
anthracene constantly transforming to anthraquinone (Figure 2 - pathways a to c) faster than the
oxidation at benzylic position (Figure 2 - pathway b).
To estimate the recyclability of the catalytic system (CuCl2/[hmim]Br), after extracting
the crude reaction with diethyl ether, the remaining ionic liquid was reused as such for next
cycles. The recovery ionic liquid could reuse and recycle at least nine times under the same
optimum condition without significant loss of the productivity (Figure 3).

ACCEPTED MANUSCRIPT
Catalysis Communications
99
98
98
98
97
97
97
95
95
100
80
60
40
20
0
1
2
3
4
5
6
7
8
9
Recycling times
Figure 3. Recyclability study of CuCl2/[hmim]Br on
aromatization of -terpinene
Moreover, this system was applied to different types of substrates in order to study
generality of this new catalytic system. The aromatization of indoline (Table 3, entry 1), 1H-
indole as the expected product was generated not in high yield. It may be due to over reaction of
the product because Cu salt could cause polymerization of pyrrole ring at N-H position [20-22].
To avoid the side-reaction, the substrate was deactivated an amine group with protecting
compounds. The aromatization process is demonstrated focusing on the effects of N-substitution
of indoline.
The corresponding indoles (2), which were desired to be able to easily remove the
protecting group, and turned into the desired indole (3) under simple conditions, were
synthesized from the aromatization of various N-protected indolines (1) under the
aforementioned protocol. According to Table 3, the presence of benzyl (Bn) protecting group
(Table 3, entry 2) not only increased the product yield, but surprisingly also generated 1H-indole
(3). It is probably due to the de-protecting process being competitively proceeded. On the other
hand, other N-protected substrates (Table 3, entries 3-5) afforded those expected indoles as the
only product without any traces of the de-protecting product. The substitution of protecting
group like tert-butyloxycarbonyl (t-Boc), benzoyl (Bz), and p-toluenesulfonyl (Ts) groups are
practically stable towards oxidation under various oxidizing agents [23]. Those substitutions,
which deactivated the substrate barely generated the products; whereas after applying twice

ACCEPTED MANUSCRIPT
Catalysis Communications
amounts of TBHP and using longer reaction time, their expected products were observed up to
40% as their best yield.
Table 3. Aromatization ofindolines in [hmim]Bra
Substrate
Product
Yield
(% )b
Entry
(1)
(2)
1
39
65
2
(9)c
3d
40
(45)e
4d
5d
24
(43)e
0
(40)e
a General condition:substrate (1mmol), 5 mol CuCl2,
TBHP (3.0 eq),[hmim]Br, RT, 15 min
b
GC yield with biphenylas the internalstandard
c 1H-Indole
d
Using TBHP (6.0 eq),30 min
e The best yield ofeach reaction
All cases of N-protected indolines demonstrated that substitutions at N-position greatly
affected the product yield because of the difference of the substrate stabilities. Even though, this
catalytic system could not directly aromatize indoline into 1H-indole in high yield, those

ACCEPTED MANUSCRIPT
Catalysis Communications
N-protected indoles were smoothly removed from the reaction mixtures and then subsequently
used as substrates for the next process to synthesize the desired indole (3).
4. Conclusions
A new, simple and efficient aromatization of cyclic dienes using CuCl2/[hmim]Br as a
new recyclable catalytic system in the presence of TBHP was presented. For aromatization of
indolines which scarcely reported under IL system, this protocol also showed great reactivity in
the aromatization step.
Acknowledgements
We gratefully thank Center of Excellence in Natural Products Chemistry, Department of
Chemistry, Faculty of Science, Chulalongkorn University, and the 90th Anniversary of
Chulalongkorn University Scholarship for the provision of chemicals and laboratory facilities.
Financial support from the Thailand Research Fund in the form of Royal Golden Jubilee Ph.D.
Fellowship (grant no. PHD/0215/2553).
Appendix A. Supplementary data
Supplementary data to this article can be found online at

ACCEPTED MANUSCRIPT
Catalysis Communications
References
[1] P.P. Fu, R.G. Harvey, Chem. Rev. 78 (1978) 317-361.
[2] G. Srinivas, M. Periasamy, Tetrahedron Lett. 43 (2002) 2785-2788.
[3] G.S. Ananthnag, A. Adhikari, M.S. Balakrishna, Catal. Commun. 43 (2014) 240-243.
[4] M.M. Heravi, F.K. Behbahani, H.A. Oskooie, R.H. Shoar, Tetrahedron Lett. 46 (2005)
2775-2777.
[5] M.A. Bigdeli, A. Rahmati, H. Abbasi-Ghadim, G.H. Mahdavinia, Tetrahedron Lett. 48
(2007) 4575-4578.
[6] K. Yamamoto, Y.G. Chen, F.G. Buono, Org. Lett. 7 (2005) 4673-4676.
[7] N. Ngamsomprasert, in: Department of Chemistry, Chulalongkorn University, Bangkok,
2011.
[8] P. Weyler, Encyclopedia of Toxicology, 2nd ed., Elsevier, New York, 2005.
[9] G. Tojo, M.I. Fernandez, Oxidation of Alcohols to Aldehydes and Ketones, Springer,
London, 2006.
[10] B.S. Chhikara, R. Chandra, V. Tandon, J. Catal. 230 (2005) 436-439.
[11] S.B. Lee, J.C. Lee, Bull. Korean Chem. Soc. 30 (2009) 3107-3108.
[12] L. Marinescu, M. Mølbach, C. Rousseau, M. Bols, J. Am. Chem. Soc. 127 (2005) 17578-
17579.
[13] D. Betz, P. Altmann, M. Cokoja, W.A. Herrmann, F.E. Kühn, Coord. Chem. Rev. 255
(2011) 1518-1540.
[14] J. Muzart, Adv. Synth. Catal. 348 (2006) 275-295.
[15] Y. Li, X. Wu, T.B. Lee, E.K. Isbell, E.J. Parish, A.E. Gorden, J. Org. Chem. 75 (2010)
1807-1810.
[16] Y. Shen, Z. Tan, D. Chen, X. Feng, M. Li, C.C. Guo, C. Zhu, Tetrahedron 65 (2009) 158-
163.
[17] S. Rayati, S. Zakavi, M. Koliaei, A. Wojtczak, A. Kozakiewicz, Inorg. Chem. Commun. 13
(2010) 203-207.
[18] X. Ye, C. Xie, Y. Pan, L. Han, T. Xie, Org. Lett. 12 (2010) 4240-4223.
[19] L. Vereecken, J. Peeters, Chem. Phys. Lett. 333 (2001) 162-168.
[20] H.M. Meshram, G.S. Reddy, M.M. Reddy, B. Eeshwaraiah, J.S. Yadav, Indian J. Chem.
42B (2003) 2615-2617.
[21] L.-H. Zhai, L.-H. Guo, Y.-H. Luo, Y. Ling, B.-W. Sun, Org. Process Res. Dev. 19 (2015)
849-857.
[22] M.V. Karkhelikar, V.V. Rao, S.S. Shinde, P.R. Likhar, Tetrahedron Lett. 57 (2016) 4803-
4806.
[23] T.W. Green, P.G.M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience,
New York, 1999.

ACCEPTED MANUSCRIPT
Catalysis Communications

ACCEPTED MANUSCRIPT
Catalysis Communications
Highlights
 Optimize conditions with various parameters in ILs
 Use commercially available materials to synthesized ILs
 Display the recyclability of the catalytic system
 Investigate the scope of the reaction with various substrates