An investigation of the catalytic potential of mono- and dicationic imidazolium N-heterocyclic carbenes in the benzoin condensation

Article abstract of DOI:10.1016/j.tetlet.2010.06.099

The catalytic potential of imidazolium salts in the benzoin condensation was investigated. Various aromatic aldehydes were tested in the benzoin condensation under the optimised protocol to afford α-hydroxyketones using N-heterocyclic carbenes derived from mono- and dicationic imidazolium salts. The products were obtained in good yields within short reaction times. Dicationic imidazolium salts with a long aliphatic chain between the imidazole rings were found to be more effective pre-catalysts for the benzoin condensation in comparison to the corresponding monocationic salts having the same aliphatic chain length.

Full text of DOI:10.1016/j.tetlet.2010.06.099

Tetrahedron Letters 51 (2010) 4509–4511
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Tetrahedron Letters
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An investigation of the catalytic potential of mono- and dicationic imidazolium
N-heterocyclic carbenes in the benzoin condensation
*
Murat Emrah Mavis, Cigdem Yolacan , Feray Aydogan
Department of Chemistry, Yildiz Technical University, Davutpasa Campus, 34010 Esenler, Istanbul, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic potential of imidazolium salts in the benzoin condensation was investigated. Various aro-
Received 30 April 2010
Revised 7 June 2010
Accepted 18 June 2010
Available online 25 June 2010
matic aldehydes were tested in the benzoin condensation under the optimised protocol to afford
a-
hydroxyketones using N-heterocyclic carbenes derived from mono- and dicationic imidazolium salts.
The products were obtained in good yields within short reaction times. Dicationic imidazolium salts with
a long aliphatic chain between the imidazole rings were found to be more effective pre-catalysts for the
benzoin condensation in comparison to the corresponding monocationic salts having the same aliphatic
chain length.
Keywords:
Benzoin condensation
N-Heterocyclic carbene
Monocationic imidazolium salt
Dicationic imidazolium salt
Ó 2010 Elsevier Ltd. All rights reserved.
N-Heterocyclic carbenes (NHCs) have attracted considerable
interest in recent years as effective organocatalysts. They are gener-
ated in situ from azolium salts such as thiazolium, imidazolium and
triazolium salts in the presence of weak bases and are used success-
fully in important reactions.1 Among these reactions, the benzoin
condensation is an important method for the formation of carbon–
These dicationic imidazolium salts show considerable catalytic po-
tential when compared with monocationic imidazolium salts with
long aliphatic chains, and they are also important for green
chemistry.
Mono-[CnMIM-Br] and dicationic [Cn(MIM)2-2Br] imidazolium
salts were obtained by refluxing N-methylimidazole with mono-
and dibromoalkanes in dry EtOH for 48 h according to the litera-
ture procedure8 (Scheme 1). The structures of the products were
determined from their spectroscopic data which was in accord
with those in the literature.5a–c,8 The dicationic imidazolium salt
[C6(BzIM)2-2Br] was prepared as a new chiral salt from 1-[(1S)-1-
carbon bonds starting from aldehydes giving
a-hydroxycarbonyl
compounds, which are interesting building blocks for the synthesis
of natural and pharmaceutical compounds.2 The key step of the reac-
tion is a polarity inversion of the electrophilic carbonyl carbon. Tra-
ditionally, umpolung at the carbonyl carbon in the benzoin
condensation is accomplished by using toxic cyanide anions. After
thefirstreportby Ukai,3 whoused thiamineas a pre-catalyst, various
NHCs have been used to promote the reaction effectively. The use of
pre-catalysts such as thiazolium, triazolium, imidazolium and benz-
imidazolium salts has resulted in steady improvements of the yields
and selectivities. Different reaction conditions have been studied to
obtain milder and simpler methods for the benzoin condensation.4
Dicationic imidazolium salts have been investigated widely for
their ionic liquid5 and complex formation6 properties, but, as far as
we know, there are few reports on the use of dicationic azolium
salts as pre-catalysts in benzoin condensation.7 Hence, our interest
focused on an investigation of the effect of dicationic NHCs in this
reaction. This paper describes the use, for the first time, of dication-
ic imidazolium salts with long aliphatic chains between the imi-
dazolium rings as NHC precursors in the acyloin condensation.
+
+
N
N
dry EtOH
( )n
N
N
+
2
( )n
Br
Br
N
N
reflux, 48 h
-
2 Br
C4(MIM)2-2Br, n=2
C8(MIM)2-2Br, n=6
C12(MIM)2-2Br, n=10
+
N
N
dry EtOH
reflux, 48 h
( )n
-
N
+
( )n
Br
N
Br
C4MIM-Br, n=2
C8MIM-Br, n=6
C12MIM-Br, n=10
* Corresponding author. Tel.: +90 212 3834213; fax: +90 212 3834106.
E-mail addresses: cigdemyolacan@hotmail.com, yolacan@yildiz.edu.tr (C. Yola-
can).
Scheme 1. Synthesis of the mono- and dicationic imidazolium salts.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.099

4510
M. E. Mavis et al. / Tetrahedron Letters 51 (2010) 4509–4511
+
+
dry EtOH
( )4
N
N
H
( )4
2
+
Br
N
H
Br
N
N
N
reflux, 48 h
H
-
2 Br
C6(BzIM)2-2Br
Scheme 2. Synthesis of 1,6-bis[3-(1S)-1-phenylethylimidazolium-1-yl]hexane dibromide.
Table 1
Comparison of the catalytic activities of 1,n-bis(3-methylimidazolium-1-yl)alkane dibromides [Cn(MIM)2-2Br] and 1-methyl-3-alkyl-1H-3-imidazolium bromides [CnMIM-Br]
O
O
NaOH (20 mol%)
H
2
OH
THF, reflux
catalyst
Catalyst (mol %)
Time (min)
Yielda (%)
Catalyst (mol %)
Time (min)
Yielda (%)
C4(MIM)2-2Br (1.0)
C4(MIM)2-2Br (0.5)
C4(MIM)2-2Br (0.25)
C4(MIM)2-2Br (0.1)
C4(MIM)2-2Br (0.05)
C8(MIM)2-2Br (1.0)
C8(MIM)2-2Br (0.5)
C8(MIM)2-2Br (0.25)
C8(MIM)2-2Br (0.1)
C8(MIM)2-2Br (0.05)
24
45
67
75
91
19
39
56
68
87
15
27
38
57
74
82
73
67
61
55
86
78
73
63
58
96
82
77
68
62
C4MIM-Br (1.0)
C4MIM-Br (0.5)
C4MIM-Br (0.25)
C4MIM-Br (0.1)
C4MIM-Br (0.05)
C8MIM-Br (1.0)
C8MIM-Br (0.5)
C8MIM-Br (0.25)
C8MIM-Br (0.1)
C8MIM-Br (0.05)
C12MIM-Br (1.0)
C12MIM-Br (0.5)
C12MIM-Br (0.25)
C12MIM-Br (0.1)
C12MIM-Br (0.05)
31
50
76
65
63
54
46
78
71
69
57
54
84
79
72
65
53
72
84
103
27
42
66
75
101
21
33
45
64
87
C
C
C
C
C
12(MIM)2-2Br (1.0)
12(MIM)2-2Br (0.5)
12(MIM)2-2Br (0.25)
12(MIM)2-2Br (0.1)
12(MIM)2-2Br (0.05)
a
Isolated yield.
Table 2
Synthesis of the acyloins
Aldehyde
C4(MIM)2-2Br
C8(MIM)2-2Br
C12(MIM)2-2Br
Time (min)
Time (min)
Yielda (%)
65
Time (min)
Yielda (%)
Yielda (%)
82
O
H
155
135
190
165
75
77
85
120
170
125
H3CO
O
H
215
200
72
80
84
90
H3C
O
H
O
F
CH3
H
230
100
65
76
200
85
72
87
180
60
79
95
H3C
O
H
a
Isolated yield.
phenylethyl]-1H-imidazole which was itself rapidly obtained from
(S)- -methylbenzylamine (Scheme 2) using the literature proce-
dure.9 The structure of this compound was established from its
IR and 1H NMR spectra as well as by elemental analysis.10
a

M. E. Mavis et al. / Tetrahedron Letters 51 (2010) 4509–4511
4511
The potential of the dicationic imidazolium salts in benzoin
References and notes
condensations was investigated by using benzaldehyde as the sub-
strate and 1 mol % of C8(MIM)2-2Br as the catalyst. To determine
the optimum conditions, the use of solvents such as acetonitrile,
THF and dichloromethane, and various bases including potassium
carbonate, triethylamine and sodium hydroxide was tested. It
was found that THF was the best solvent with respect to the reac-
tion rate, and NaOH was the best base for the deprotonation of the
dicationic imidazolium salts in the studied reaction. Although it
had been reported5d that NaOH causes precipitation of the acyloins
formed in the reaction as their sodium salts and retards further
reaction, in our study the formed benzoin remained in solution
in all our experiments. Under the same conditions, the C4(MIM)2-
2Br salt gave a lower yield with a longer reaction time, whereas
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C12(MIM)2-2Br gave the highest yield and the shortest reaction
time. Monocationic imidazolium salts with the same aliphatic
chain length (CnMIM-Br) were also investigated as pre-catalysts
for comparison with their dicationic analogues. The bisimidazoli-
um salts needed shorter reaction times and gave higher yields than
the monocationic salts. This can be interpreted as a result of the in-
creased number of active centres which could enhance the cata-
lytic activity. Different salt concentrations were also examined
for all of the catalysts. The results are summarised in Table 1,
and show that 1 mol % of the catalyst gave the best results in terms
of the percentage yield and short reaction times. The activity of the
bisimidazolium salts was also investigated for the benzoin conden-
sation of several aromatic aldehydes. In these reactions, 1 mol % of
the catalyst was used11 and it was observed that the yields and
reaction times were reasonably good (Table 2).
The chiral salt, C6(BzIM)2-2Br, was also investigated for the ben-
zoin condensation of benzaldehyde (80% yield, 100 min) and
p-methylbenzaldehyde (74% yield, 120 min) to investigate its cata-
lytic and enantiomeric induction potential. Although the yields
and reaction times were good, the products did not show any optical
activity.
8. Baltazar, Q. Q.; Chandawalla, J.; Sawyer, K.; Anderson, J. L. Colloids Surf. A 2007,
302, 150–156.
9. Genisson, Y.; Viguerie, N. L.; Andre, C.; Baltas, M.; Gorrichon, L. Tetrahedron:
Asymmetry 2005, 16, 1017–1023.
10. Spectroscopic data for C6(BzIM)2-2Br: IR (neat):
m 3030, 2981, 2935, 2859, 1652,
1536, 1495, 1454, 1382, 762, 699 cmÀ1 1H NMR (400 MHz, CDCl3): d 1.32–1.41
;
In conclusion, dicationic imidazolium salts with long aliphatic
chains between the imidazole rings were found to be more effec-
tive pre-catalysts for the benzoin condensation in comparison with
the monocationic salts having the same aliphatic chain length. The
condensation yields and reaction times improve with an increase
in the number of carbon atoms between the N-atoms. These cata-
lysts can be easily prepared and handled, they are stable, and their
use instead of toxic cyanide ions is important from the viewpoint
of green chemistry.
(m, 4H, CH2), 1.79–1.97 (m, 4H, CH2), 1.96 (d, J = 7.2 Hz, 6H, CH3), 4.22–4.27 (m,
4H, N–CH2), 5.78–5.83 (q, J = 7.2 Hz, 2H, CH), 7.28–7.47 (m, 10H, ArH), 7.53 (br
s, 2H, ArH), 7.64 (br s, 2H, ArH), 9.07 (s, 2H, ArH) ppm. Anal. Calcd for
C
28H36Br2N4 (588.41): C, 57.15; H, 6.17; N, 9.52. Found: C, 56.98; H, 6.32; N,
9.60.
11. Typical procedure for a benzoin condensation: To a solution of the aldehyde
(1 mmol) in THF (25 mL), the catalyst (1 mol %) and NaOH (20 mol % in 3 mL of
H2O) were added, and the mixture was heated under reflux for the appropriate
amount of time to complete the reaction, as indicated by TLC. After solvent
evaporation, the resulting solid was dissolved in H2O, and extracted with
CH2Cl2 (3 Â 25 mL). The combined organic extract was dried (MgSO4), and the
solvent was removed under reduced pressure. The residue was purified by
column chromatography on silica gel (n-hexane/EtOAc) or recrystallized from
EtOH.
Acknowledgement
We thank the Yildiz Technical University Scientific Research
Foundation (BAPK Project Number 28-01-02-02) for the financial
support.