Thiazolium salt immobilized on ionic liquid: An efficient catalyst and solvent for preparation of α-hydroxyketones

Article abstract of DOI:10.1080/10426500701501565

Aldehydes were efficiently converted to acyloins and benzoins using a new ionic liquid, 3-[2-(1-butyl-1H-imidazol-1,3-ium-3-yl)ethyl]-4,5-dimethyl-1,3- thiazol-3-ium dibromide 1. This ionic liquid is introduced as a catalyst and a solvent. Acyloins and benzoins were easily isolated from the reaction mixture via simple extraction, and the ionic liquid could be recycled for further use. Also, -hydroxy ketones with an aromatic and aliphatic substituent were prepared starting from aromatic and aliphatic aldehydes in the presence of ionic liquid 1.

Full text of DOI:10.1080/10426500701501565

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Thiazolium Salt Immobilized
on Ionic Liquid: An Efficient
Catalyst and Solvent
for Preparation of α-
Hydroxyketones
Farajollah Mohanazadeh a & Majid Aghvami b
a Institute of Industrial Chemistry, Iranian Research
Organization for Science and Technologies, Tehran,
Iran
b Department of Chemistry, Tarbiat Moallem
University, Tehran, Iran
Published online: 23 Aug 2007.
To cite this article: Farajollah Mohanazadeh & Majid Aghvami (2008): Thiazolium Salt
Immobilized on Ionic Liquid: An Efficient Catalyst and Solvent for Preparation of α-
Hydroxyketones, Phosphorus, Sulfur, and Silicon and the Related Elements, 182:10,
2467-2475
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Phosphorus, Sulfur, and Silicon, 182:2467–2475, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701501565
Thiazolium Salt Immobilized on Ionic Liquid: An Efficient
Catalyst and Solvent for Preparation
of α-Hydroxyketones
Farajollah Mohanazadeh
Institute of Industrial Chemistry, Iranian Research Organization for
Science and Technologies, Tehran, Iran
Majid Aghvami
Department of Chemistry, Tarbiat Moallem University, Tehran, Iran
Aldehydes were efficiently converted to acyloins and benzoins using a new ionic liq-
uid, 3-[2-(1-butyl-1H-imidazol-1,3-ium-3-yl)ethyl]-4,5-dimethyl-1,3-thiazol-3-ium
dibromide 1. This ionic liquid is introduced as a catalyst and a solvent. Acyloins
and benzoins were easily isolated from the reaction mixture via simple extraction,
and the ionic liquid could be recycled for further use. Also, α-hydroxy ketones with
an aromatic and aliphatic substituent were prepared starting from aromatic and
aliphatic aldehydes in the presence of ionic liquid 1.
Keywords Aldehyde; benzoin condensation; ionic liquid; thiazolium salt
INTRODUCTION
Ionic liquids have been utilized at ambient temperature as clean sol-
vents and catalysts for green chemistry1−3 and as electrolytes for
batteries,2 photochemistry,4 and electrosynthesis.5 Their vapor pres-
sure is not significant. As such, no volatile organic components will
be created.6 They can easily be separated from organic molecules by
distillation without loss of their catalytic property. Ionic liquids can
tolerate up to 300◦C allowing large kinetic control reactions. This be-
havior coupled with their good solvent properties, allows utilization
of small reactor volumes. Because of the poor nucleophilic properties
of the anions,7,8 such as [BF4] , [PF6] , [CF3CO2] , [CF3SO3]−, they
do not interfere with the organic reactions. Also, they are water and
–
–
–
Received August 23, 2006; accepted May 4, 2007.
Address correspondence to Farajollah Mohanazadeh, Chemistry Department, Iranian
Research Organization for Science and Technology, P.O. Box 37575-111, Tehran, Iran. E-
mail: fmohanazadeh@yahoo.com
2467

2468
F. Mohanazadeh and M. Aghvami
air insensitive and possess remarkably high thermal stability.9 Many
of these materials are derived from the 1-alkyl-3-methylimidazolium
cation. By changing the anion or the alkyl chain at the cation, a wide
variation in properties such as hydrophobicity,10,11 viscosity, density,
and solvation can be obtained. Although ionic liquids were initially in-
troduced as alternative green reaction media, today they have marched
far beyond this border, showing their significant role in controlling the
reaction as catalyst.12,13 Herein, we report the dramatic influence of
a new tailor-made, task-specific, and stable ionic liquid, 3-[2-(1-butyl-
1H-imidazol-3-ium-3-yl)ethyl]-4,5-dimethyl-1,3-thiazol-3-ium bromide
1 (Scheme 1), in benzoin condensations.
SCHEME 1
Benzoin condensation was traditionally catalyzed by cyanide anion
and thiazolium salts. Also, a number of heterocyclic systems such as
immobilized imidazole,14 triazoles,15,16 and thiazoles were used for ben-
zoin condensation.17 However; we have found that a specific ionic liq-
uid efficiently promotes the benzoin condensation. By use of this ionic
liquid, 3-[2-(1H-imidazol-3-ium-3-yl) ethyl]4,5-dimethyl-1,3-thiazol-3-
ium dibromide 1, we were successful in catalysing benzoin type con-
densations within a reasonable period of time (Table I) with high to
moderate yields.
RESULTS AND DISCUSSION
At first, 4-methyl-5-(2-hydroxyethyl) thiazole was selected for the
preparation of the ionic liquid. It is easily obtained from the sulfite
cleavage of thiamine.19 The ionic liquid, 3-[2-(1-butyl-1H-imidazol-
3-ium-3-yl)ethyl]-5-(hydroxyethyl)-4-methyl-1,3-thiazol-3-ium dibro-
mide 2 (Scheme 1), was obtained by reaction of 1-butylimidazole
with 3-(2-bromoethyl)-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium
bromide 4. Compound 4 is prepared by reaction of 4-methyl-5-(2-
hydroxyethyl) thiazole with 1,2-dibromoethane. Benzoin is obtained

Thiazolium Salt Immobilized on Ionic Liquid
2469
from the reaction of benzaldehyde in the ionic liquid 2 in the presence
of triethylamine (2 equiv.) and ethanol (2 equiv.). We have found,
however, that the presence of the 5-(2-hydroxyethyl) group decreases
the activity of the catalyst, possibly by providing an alternate and
competing route (Scheme 2b), which leads to the formation of a fused
perhydrofurothiazoline ring system (12). This has been shown for
2-(1-hydroxyalkyl) and 2-(1ꢀ-hydroxyaryl) derivatives of thiamine in
protic20 and aprotic21 media under the influence of a variety of bases.
It should be noted that the presence of the 4,5 double bond of the
thiazolium nucleus is of crucial importance in restoring the aromatic
character of the thiazolium ring in the transition state of the reaction.
This, in fact, is equivalent to the conversion of enamine 10 to imine 11,
whose formation is essential for the production of acyloin and benzoin
(Scheme 2a).
SCHEME 2
4,5-Dimethylthiazole is the better choice for the preparation of the
catalyst. 4,5-Dimethylthiazole was mixed with 1,2-dibromoethane at
110◦C for 6 h. The resulting thiazolinium bromide 3 was reacted with
1-butylimidazole in DMF, which afforded the ionic liquid 1. The new
ionic liquid 1 is used as the catalyst and solvent for the preparation
of benzoins and acyloins. The major advantage of this method is the
simple recovery of catalyst and solvent, thus providing a convenient
economical synthesis of these classes of compounds. Furthermore, the
present approach is superior, not only with respect to the yields, but
also in its range of applicability as compared to the cyanide catalyzed
benzoin condensation. For example, whereas our method results in 90
% yield of furoin (Table I), the benzoin condensation of 2-furaldehyde
affords furoin in low yield. Also, by use of this new ionic liquid 1 we
obtained 4,4ꢀ-dinitrobenzoin (Table I) in 85% yield; its preparation is
not possible by the classical benzoin condensation method.
In the case of acyloins, although the yields were lower relative to
those of benzoins, from an economical point of view and because of

2470
F. Mohanazadeh and M. Aghvami
TABLE I Synthesis of Acyloins and Benzoins
Acyloins, benzoins
Yielda (%)
Time (h)
Butyroin
Palmitoin
80
51
92
90
85
83
96
96
12
12
12
12
Benzoin
Furoin
4,4ꢀ-Dinitrobenzoin
4,4ꢀ-Dimethylbenzoin
aComparison of spectral data (IR, NMR, UV) and
thin layer chromatography with authentic sample also
confirmed structure and purity of the reported acyloins
and benzoins.
the ease of experimental procedure this approach is prefered over the
standard acyloin condensation.
In the case of benzoins (Table I) additional stability of the imine α-
carbanion (11, Scheme 2), is provided by the resonance contribution
of the aromatic ring. This, in turn, results in good yields and short
reaction times. For acyloins, longer reaction times are required due to
the absence of such resonance stabilization (Table I). Furthermore, a
low yield may be expected for palmitoin because of the hindrance in the
approach of its large prerequisite aldehyde molecule to the thiazolium
nucleus.
A variety of bases may be used to generate the catalytically ac-
tive thiazolium ion.21−23 The use of hydroxides was avoided since they
are known to also cause opening of the thiazolium ring and render it
inactive.24 Alkoxides were also not considered since they are known to
be excellent catalysts for aldol condensation of aliphatic aldehydes. Tri-
ethylamine, on the other hand, is a poor catalyst for aldol condensation
and is incapable of opening the thiazolium ring. We have found that the
use of two equivalents of triethylamine produces optimal yields.
The convenience of this experimental procedure encouraged us to
evaluate the potential use of the ionic liquid 1 in the synthesis of com-
pounds of the type RꢀCOCHOHRꢀꢀ where Rꢀ = aryl and Rꢀꢀ = alkyl, or
vice versa (Scheme 3).
SCHEME 3

Thiazolium Salt Immobilized on Ionic Liquid
2471
SCHEME 4
At first glance, the major shortcoming of such an approach would
appear to be the equivalent possibility of concomitant formation of four
different products. However, on further inspection it seems reasonable
to assume that formation of 5 and 7 is favored over 6 and 8. This is
based on the fact that in the case of 5 and 7 the transition state of
the reaction involves an imine α-carbanion which is further stabilized
by resonance contribution of the aromatic ring (14, Scheme 4). Such
a transition state is lower in energy and is therefore expected to be
reached easier as compared to the transition state for the formation of
6 or 8 in which resonance stabilization is absent (13, Scheme 4). In fact,
whereas benzoins are formed in 90% yields within a few hours with the
ionic liquid 1, acyloins could only be obtained in moderate to good yields
after four days (see Table II).
It appears reasonable to assume that formation of benzoin (7, Scheme
3) may be suppressed by keeping the concentration of the aromatic alde-
hyde low during the course of the reaction, since most of the aromatic
TABLE II Synthesis of Compounds 5–8
Condition
5 + 6
7
8
(a)
(b)
(c)
(d)
73
62
57
43
6
n.d
n.d
n.d
n.d
10
14
20
(a) Both aldehydes added simultaneously.
(b) 1/2 Benzaldehyde added with acetaldehyde
and 1/2 added after 24 h.
(c) 1/4 Benzaldehyde added with acetaldehyde
and the rest added in 24 h intervals.
(d) Benzaldehyde added dropwise to the
reaction mixture during 3 days.
n.d = not determined.

2472
F. Mohanazadeh and M. Aghvami
aldehyde would be presented in the form of “active aldehyde”25−27 (14,
Scheme 4) and little free aldehyde would be available for benzoin forma-
tion. It should be noted, however, that a low concentration of aromatic
aldehyde and a very high concentration of aliphatic aldehyde would
have two undesirable consequences. First, most of the catalyst would
be tied up in the form of “active aliphatic aldehyde,” leading mainly
to the formation of acetoin and a very small amount of 6 (Scheme 3).
Second, with diminishing availability of aliphatic aldehyde (due to ace-
toin formation), production of 5 and 6 will decrease, and the aromatic
aldehyde will have no choice but to self condense (benzoin formation,
see Table II).
It is, therefore, clear that to obtain good yields of 5 (or 6), there should
be an excess of aliphatic aldehyde available to the “active aromatic alde-
hyde.” The use of an of excess aliphatic aldehyde and the reversibility
of the formation of the “active aliphatic aldehyde” (vide supra) would
fulfill such a requirement.
To test these hypotheses, we used a 2 : 2 : 2 : 10 : 20 molar ratio of
ionic liquid 1 : triethyl amine : ethanol : benzaldehyde : acetaldehyde
in a set of experiments. All reactions were run for four days with the
only variable parameter being the mode of addition of the aromatic
aldehyde to the reaction mixture. As shown in Table II, the best yield
was obtained under condition a (Table II).
It is evident that due to the presence of triethylamine in the reaction
medium, equilibrium may be established between 5 and 6 by simple
keto-enol tautomerism. In most cases we observed a ca. 2 : 1 ratio of
1
5 : 6 by H NMR. This, however, presents no difficulty since 6 may be
quantitatively converted to 5 in ethanol using trace amounts of potas-
sium carbonate (see Experimental). Furthermore, the conversion of 5
to 6 have also been reported to proceed in quantitative yields in both
acidic and basic media.28−30 Conversion of 5 to 6 under the influence of
carboligase has also been reported.29−32
It should be noted that the synthesis of 5 or 6 by conventional means
of C-C bond formation involves multi-step reaction sequences, leading
to very poor yields of the hydroxy ketones.28,30,33−36 Biochemical syn-
thesis of these compounds involving thiamine-containing enzymes, also
results in very poor yields.32 In the present approach—due to the nature
and conditions of the reaction—formation of acetoin and some benzoin
is unavoidable. Nevertheless, these compounds, which are valuable in
their own rights, may be easily separated from 5 and 6 by distillation
because of the large differences in their boiling points.
It should be mentioned that, the presence of ethanol or isopropanol
is necessary for the promotion of the reaction. For example, benzoin
is obtained in 92% yield in the presence of ethanol. Under the same

Thiazolium Salt Immobilized on Ionic Liquid
2473
conditions in the absence of ethanol the yield of the reaction was found
to be 40%.
The solvent-catalyst is regenerated by heating at 70◦C for 30 min un-
der reduced pressure, mixing with ether containing 1% HCl, decanting,
and heating at 80◦C under vacuum for 30 min. It is advisable to devote
a batch of the solvent-catalyst to one type of reaction. In this manner,
after 5 cycles the same batch of ionic liquid was found to catalyze the
benzion condensation of benzaldehyde in 90% yield.
EXPERIMENTAL
1
The H NMR spectra were measured with a Jeol JNM-PMX60 spec-
trometer. Infrared spectra were obtaind with a Perkin-Elmer 267 spec-
trophotometer. Thin layer chromatography was performed on silica gel
(Macerey-Nagel Co., Plygram Sil G/uv 254). All chemicals were pur-
chased from Aldrich.
3-(2-Bromoethyl)-4,5- dimethyl-1,3-thiazol-3-ium Bromide (3)
4,5-Dimethylthiazole (45.2 g, 0.4 mol) and 1,2-dibromoethane (75.2 g,
0.4 mol) were heated together in an oil bath (110◦C) for 6 h. After cooling
acetone (200 mL) was added and the crude solid product was filtered off
and washed with acetone (2 × 50 mL). The precipitate was collected and
1
recrystallized from ethanol / ether (2 : 1), mp = 185–186◦C. H NMR
(DMSO-d6): δ = 10.3 (s, 1H), 5.1 (t, J = 6.2 Hz, 3H), 4.1 (t, J = 6.2 Hz,
3H), 2.6 (s, 6H).
3-[2-(1-Butyl-1H-imidazol-3-ium-3-yl)ethyl]-4,5-dimethyl-1,3-
thiazol-3-ium Dibromide (1)
1-Butylimidazole (12.4 g, 0.1 mol) and 3-(2-bromoethyl)-4,5-dimethyl-
1,3-thiazol-3-ium bromide (30.1 g, 0.1 mol) were allowed to react in
DMF (100 mL) for 60 min at 110◦C. The mixture was then diluted with
diethyl ether (300 mL). The ether was decanted and fresh ether was
added; this step was repeated twice. After the third decanting of ether,
any remaining ether was removed by heating the mixture to 60◦C and
stirring while on a vacuum line. The pure oily product was obtained in
1
quantitative yield. H NMR (DMSO-d6): δ = 10.3 (s, 1H), 9.6 (s, 1H),
8.1 (s, 1H), 8.0 (s, 1H), 4.9 (br. s, 4H), 4.3 (t, J = 7.2 Hz, 2H), 2.6 (s, 6H),
1.6 (q, J = 7.2 Hz, 2H), 1.2 (m, 2H), 0.8 (t-like, 3H).

2474
F. Mohanazadeh and M. Aghvami
General Procedure for Preparation of Acyloins and Benzoins
A three-neck flask equipped with nitrogen inlet and outlet tubes and
reflux condenser was charged with ionic liquid (85 g, 0.2 mol), ethanol
(9.2 g, 0.2 mol), and triethylamine (20.2 g, 0.2 mol). To the stirring
mixture—under nitrogen atmosphere—we added 1 mole of freshly dis-
tilled aldehyde. The mixture was heated at 80◦C for the time spec-
ified in Table I and then allowed to cool to room temperature. The
mixture was extracted with ethyl acetate (2 × 50 mL). The ethyl ac-
etate was removed under reduced pressure. Palmitoin, benzoin, furoin,
4,4ꢀ-dinitrobenzaldehyde, and 4,4’-dimethylbenzaldehyde were recrys-
tallized from ethanol. Bytyroin was purified by vacuum distillation.
Preparation of Compounds 5–8
Ionic liquid 1 (85 g, 0.2 mol), ethanol (9.2 g, 0.2 mol), and triethylamine
(20.2 g, 0.2 mol) were mixed at room temperature. Under nitrogen atmo-
sphere, a mixture of acetaldehyde (88 g, 2 mol) and benzaldehyde (106
g, 1 mol) were added dropwise to the suspension. After 4 days at room
temperature, the reaction mixture was extracted with ethyl acetate.
Ethyl acetate, ethanol and acetoin were removed from the mixture by
distillation at atmospheric pressure. The residue, distilled under re-
duced pressure, gave a mixture of 5 and 6 (bp13: 130–135◦C). Benzoin
(m.p.: 136–137◦C) was separated from the residue by crystallization
from ethanol.
Conversion 1-Hydroxy-1-phenylpropane-2-one (6) to 2-
Hydroxy-1-phenylpropane-1-one (5)
A mixture of 5 and 6 (3 g, 0.02 mol) in ethanol (40 mL) was added to
a solution of sodium potassium carbonate (0.276 g, 0.002 mol) in water
(15 mL). After 8 days at room temperature, the mixture was extracted
with ether. The ethereal layer was dried and evaporated to dryness.
The product was obtained as a pure oil (100%).
REFERENCES
[1] J. D. Holbrey and K. R. Seddon, Clean Products and Process,1, 223 (1991).
[2] T. Welton, Chem. Rev., 99, 2071 (1999).
[3] R. D. Rogers and K. R. Seddon, Ionic Liquids: Industrial Application to Green Chem-
istry, (ACS, Washington DC, 2002). ACS Symposium Series 818.
[4] C. M. Gordon, A. J. McLean, M. J. Muldoon, and I. R. Dunkin, Photochemistry in
Ionic Liquids, (ACS, Washington DC, 2002) ACS Symposium Series 818.
[5] W. Lu, A. G. Fadeev, B. Qi, and B. R. Mattes, Synth. Met., 139, 136 (2003).

Thiazolium Salt Immobilized on Ionic Liquid
2475
[6] C. L. Hussey, Pure Appl. Chem., 60, 1763 (1988).
[7] S. T. Handy, M. Okello, and G. Dickenson, Org. Lett., 5, 2513 (2003).
[8] L. C. Branco and C. A. M. Afonso, J. Org. Chem.,69, 4381 (2004).
[9] H. L. Ngo, K. LeCompt, L. Hargens, and A. B. McEwen, Thermochim. Acta, 357, 97
(2000).
[10] J. G. Huddleston, A. E. Visser, W. M. Reichert, H. D. Willauer, G. A. Broker, and R.
D. Rogers, Green Chem., 3, 156 (2001).
[11] D. Bonhote, A. P. Dias, N. Papageogiou, K. Kalyanasundaram, and M.Gratzel, Inorg.
Chem., 35, 1168 (1996).
[12] G. Yanlong, S. Feng, and D. Yoiquan, Catal. Commun.,4, 597 (2003).
[13] B. C. Ranu and S. Banerjee, Org. Lett.,7, 3049 (2005).
[14] J. M. D. Storey and C. Williamson, Tetrahedron Lett.,64, 7337 (2005).
[15] D. Enders and U. Kallfass, Angew. Chem. Int. Ed.,41, 1743 (2002).
[16] D. Enders, K. Breuer, U. Kallfass, and T. Balensiefer, Synthesis, 8, 1292 (2003).
[17] R. L. Knight and F. J. Leeper, Tetrahedron Lett., 38, 3611 (1997).
[18] C. A. Dvorak and H. V. Rawal, Tetrahedron Lett., 39, 2925 (1998).
[19] R. R. Williams, R. E. Waterman, and E. R. Buchman, J. Am. Chem. Soc., 57, 536
(1935).
[20] K. Karimian, M. Askari, M. Farahani, and N. Sachinvala, Synthesis, 48 (1981).
[21] A. Takamizawa, K. Hiari, K. Hamushima, and S. Mitsumoto, Tetrahedron Lett.,
5071 (1967).
[22] K. Karimian, F. Mohtarami, and M. Askari, J. Chem. Soc. Perkin Trans. II, 1538
(1981).
[23] H. Stetter and G. Dambkes, Synthesis, 403 (1977).
[24] T. C. Bruice and S. Benkovic, Bioorganic Mechanisms (W. A. Benjamin Inc., New
York, 1966) Vol. 2.
[25] J. P. Kuebrich and R. L. Schowen, J. Am. Chem. Soc., 93, 1220 (1971).
[26] J. P. Kuebrich, R. L. Schowen, S. M. Wang, and M. E. Lupes, J. Am. Chem. Soc., 93,
1241 (1971).
[27] J. Correia, J. Org. Chem., 48, 3343 (1983).
[28] T. I. Teminkova, J. Gen Chem., USSR, 10, 468 (1940).
[29] E. M. Kotchergine, Bull. Soc. Chim., 43, 573 (1928).
[30] A. Favorskii, Bull. Soc. Chim., 39, 216 (1926).
[31] K. V. Auwers and H. Mauss, Biochem. Z., 192, 200 (1928).
[32] K. V. Auwers, Biochem. Z., 289, 390 (1937).
[33] G. Richard, Compt. Rend., 214, 673 (1942).
[34] P. L. Jullian and J. Oliver, J. Org. Synth. Coll., II, 391 (1943).
[35] K. Kaji and H. Nagshima,J. Pharm. Soc. Japan, 76, 1247 (1956).
[36] M. Tsuruga, Japanese Patent 5624, Chem. Abstr., 51, 1557i (1955).