An eco-compatible pathway to the synthesis of mono and bis-multisubstituted imidazoles over novel reusable ionic liquids: An efficient and green sonochemical process

Article abstract of DOI:10.1039/c8ra02755b

Novel and environmentally benign ionic liquids (ILs) comprised of DABCO were successfully synthesized. These ILs were used as robust catalysts for the sonochemical one pot multi-component synthetic route for the functionalized annulated imidazoles in water with excellent yields. The present protocol scored well in terms of yield economy as compared with the conventional procedures. The merits of the current green method include simplicity, applicability, broad functional groups tolerance, clean reaction profiles, and no tedious work-up and they give high-to-quantitative yields. From the environmental viewpoint, these eco-friendly green catalysts can be effortlessly retrieved and reused at least seven successive times without substantial loss in catalytic activity.

Full text of DOI:10.1039/c8ra02755b

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An eco-compatible pathway to the synthesis of
mono and bis-multisubstituted imidazoles over
novel reusable ionic liquids: an efficient and green
sonochemical process†
Cite this: RSC Adv., 2018, 8, 16392
ab
*
Wael Abdelgayed Ahmed Arafa
Novel and environmentally benign ionic liquids (ILs) comprised of DABCO were successfully synthesized.
These ILs were used as robust catalysts for the sonochemical one pot multi-component synthetic route
for the functionalized annulated imidazoles in water with excellent yields. The present protocol scored
well in terms of yield economy as compared with the conventional procedures. The merits of the
current green method include simplicity, applicability, broad functional groups tolerance, clean reaction
profiles, and no tedious work-up and they give high-to-quantitative yields. From the environmental
viewpoint, these eco-friendly green catalysts can be effortlessly retrieved and reused at least seven
successive times without substantial loss in catalytic activity.
Received 29th March 2018
Accepted 24th April 2018
DOI: 10.1039/c8ra02755b
rsc.li/rsc-advances
evolution of the synthetic protocols for imidazoles preparation
has attracted continued interest among medicinal and organic
chemists.9 Among these protocols, the multicomponent cyclo-
Introduction
Multicomponent reactions (MCRs) have been demonstrated to
be signicantly successful in producing the desired complex
products from readily obtainable materials in a single synthetic
reaction that comprises three or more substrates.1 The creating
of novel MCRs and improving of published MCRs are presently
under intensive focus due to their broad scope of applications
in modern drug design.2 One of these applications is the
assembly of multisubstituted imidazoles. The heterocyclic
molecules comprised of an imidazole moiety whether synthetic
or naturally occurring exhibit an array of pharmacological
activities and play substantial roles in biochemical processes.
They are well-known as anti-inammatory agents, P38 MAP
kinase inhibitors, fungicides, herbicides, therapeutic and
antithrombotic agents.3 As well, imidazole derivatives are
employed in photography as photosensitive molecules.4 More-
over, several imidazole derivatives are utilized as IL-1 biosyn-
thesis inhibitors and eclectic antagonists for the glucagon
receptors.5 In addition, the skeleton of many drug molecules
such as eprosartan and trifenagrel, as well numerous biological
compounds such as histamine and histidine, comprise imid-
azole moieties.6 Applications such as N-heterocyclic carbenes in
catalysts design7 and ILs in green chemistry8 are some other
important merits of the imidazoles derivatives. Recently, the
condensation reaction of diverse aldehydes, 1,2-dicarbonyl
compounds (benzils or benzoins), and a nitrogen exporter that
is widely utilized for the design of multisubstituted imidazole
derivatives with alteration of catalysts and parameters.10
Nevertheless, some of these synthetic procedures associated
with more than one serious drawback such as acidic media, low
yield, long reaction time, formation of by-products and intricate
work up and purication. Furthermore, the construction of
such heterocyclic molecules has been commonly performed
using polar solvents, for example, acetic acid (AcOH) and N,N-
dimethylformamide (DMF) resulting in recovery procedure and
complex isolation. Thus, presenting novel and green catalysts
having excellent recyclability is an essential task for synthetic
organic chemists to gain control over these deciencies and
satisfy the standards of an environmentally benign, effective
and mild procedures for the assembly of imidazoles. As of late,
from a green chemistry standpoint, the evolution of sustainable
protocols requires the utilization of sustainable catalysts and
benign solvents. From this aspect, ILs displayed good catalytic
activities as a result of their negligible vapor pressure, recovery
from reaction mixture, selectivity, reusability and capability to
dissolve plentiful of substrates.11 ILs were successfully utilized
as catalyst and solvent for assortment of reactions that have
many applications in organic preparations and industry.12
Solvents, the most essential parameter of the ecological
performance, are another factor, which ought to be thought
about in green procedures especially in chemical manufacture
processes. Usage of environmentally preferable solvents, such
aChemistry Department, College of Science, Jouf University, P. O. Box 72341, Sakaka,
Aljouf, Kingdom of Saudi Arabia
bChemistry Department, Faculty of Science, Fayoum University, P. O. Box 63514,
Fayoum City, Egypt. E-mail: waa00@fayoum.edu.eg
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra02755b
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as water, found to be diminished the environmental inuences
that resulting from the utilization of other organic solvents in
chemical production.13 Ultrasound-accelerated organic chem-
ical reactions are acquiring a great interest in several chemistry
research branches.14 Ultrasound irradiation displayed an alter-
native source of energy for organic synthesis, which proceed by
the generation, growth and collapse of acoustic bubbles in the
reaction mixture. These straightforwardly help in lessening the
reaction duration and enhancing the reaction outcome.15 In the
current work, an endeavor has been made for the construction
of mono- and bis-multisubstituted imidazoles in water under
sonication within few minutes using new ILs as an eco-friendly,
reusable and sustainable catalysts. Aer carefully literature
survey, we can believe that this is the rst report of design,
preparation, and characterization of ionic liquids 3a–c (Scheme
1) and their application as catalyst in organic syntheses
(Schemes 2–5).
Scheme 2 Synthesis of 2,4,5-triphenyl-1H-imidazole 6a.
the outcomes are summed up in Table 1. From these results
(Table 1), we observed that this cyclo-condensation reaction
could be effectively catalyzed by any one of the ILs (3a–c) and
afforded the required product (6a) in moderate yields (Table 1,
entries 1–4).
The template reaction (Scheme 2) was proceeded well under
the catalytic inuence of diversied DABCO based catalysts. The
preferable outcome was acquired with acetate catalyst (3a),
furnished 6a in 94% yield aer 20 min (Table 1, entry 1). The
other catalysts afforded lesser yields in a longer reaction times
(Table 1, entries 2–4) with the relative catalytic potential
following the order AcO > BF4 z PF6 > Cl. To recognize the
function of hydroxyl groups in the current catalytic system, two
separately reactions with 5 mol% of each 3a and DABCO were
employed under the optimized reaction conditions. As obvious
from Table 1, lower reaction rate and hence lower yield are
detected with DABCO (Table 1, entry 5), which distinctly indi-
cating that hydroxyl groups are the active centre in catalyst core
and responsible for promoting this reaction. When carried out
the template reaction without using catalyst, no product was
observed even aer stirring for 2 h (Table 1, entry 6). So, in the
next studies, catalyst [DABCO-DOL][OAc] (3a) will be utilized as
the optimal choice for further investigation. Further improve-
ments in both reaction yield and reaction rate were observed on
running the aforementioned reaction (Scheme 2) under ultra-
sonic irradiation (40 kHz, Table 1, entries 7–10).
Results and discussion
In the context of our search for the evolution of eco-friendly and
efficacious protocols for the construction of biologically
signicance heterocyclic compounds,16 we studied the prepa-
ration of substituted imidazoles as potential drug derivatives,
utilizing novel ILs (3a–c) as catalysts (Scheme 1). Initially, ILs
(3a–c) were prepared from commercially available 1,4-diazo-
bicyclo[2.2.2]octane (DABCO) and 2-chloro-1,3-propandiol (1),
followed by the reaction with different salts for anion exchange
(Scheme 1). The structure of the prepared ILs was elucidated
from their FT-IR, NMR, and elemental analyses. Further, these
ILs can be employed effectively in water that is compatible with
“green chemistry”.17
In order to assess the catalytic efficacy of the newly synthe-
sized ILs and to determine the most convenient reaction
conditions; the three component reaction (3-MCR) of benzal-
dehyde (4a, 1 mmol), benzil (5a, 1 mmol), and NH4OAc
(2.5 mmol, ammonia source) in water (5 mL) at 120 ꢀC (oil bath
temperature) was selected as the model study (Scheme 2) and
To assess the impact of catalyst loading on this reaction, the
template reaction (Scheme 2) was performed using different
amounts of IL 3a (Table 2). From the results displayed in Table
2, it was established that, 5 mol% is the optimal molar ratio of
3a that afforded the desired product in excellent yield (Table 2,
entry 4). When the molar ratio of 3a was decreased to 4 and
Table 1 Synthesis of 6a using DABCO derived catalyst systems (3a–c)a
Entry
Catalyst
Method
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
[DABCO-DOL][OAc]
[DABCO-DOL][BF4]
[DABCO-DOL][PF6]
[DABCO-DOL][Cl]
DABCO
Stirring
Stirring
Stirring
Stirring
Stirring
Stirring
US
US
US
US
20
25
27
30
60
120
20
10
5
94
88
86
77
23
NRb
99
99
99
97
None
[DABCO-DOL][OAc]
[DABCO-DOL][OAc]
[DABCO-DOL][OAc]
[DABCO-DOL][OAc]
10
3
a
4a (1 mmol), 5a (1 mmol), NH4OAc (2.5 mmol) and 3a–c (5 mol%) in
water (5 mL) at 120 ꢀC (60 ꢀC in case of US). b NR no reaction.
Scheme 1 Synthesis of diol functionalized ILs and exchange of anion.
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Table 2 Effect of catalyst loading during the assembly of 6aa
Table 4 The effect of diverse ammonium salts as the nitrogen source
on preparation of 6aa
Entry
Catalyst (mol%)
Time (min)
Yield (%)
Entry
Nitrogen source
Equiv.
Time (min)
Yield (%)
1
2
3
4
5
6
1
3
4
5
8
10
30
15
7
5
5
73
89
97
99
99
99
1
2
3
4
5
6
NH4OAc
NH4OAc
NH4Cl
NH4HCO3
(NH4)2CO3
HCOONH4
1
2.5
3
3
3
5
5
10
10
10
15
91
99
88
82
85
55
5
3
a
The mixture of 4a (1 mmol), 5a (1 mmol), NH4OAc (2.5 mmol) and 3a
in water (5 mL) was sonicated at 60 ꢀC.
a
The mixture of 4a (1 mmol), 5a (1 mmol) and 3a (5 mol%) in water (5
mL) was sonicated at 60 ꢀC using different ammonium salts.
3 mol%, the yields were also high, whilst the rates were
diminished (Table 2, entries 2 and 3). Moreover, when the
catalyst molar ratio was further diminished to 1 mol%, the
required product was acquired in moderate yield with notable
decrease of the rate (Table 2, entry 1). Whereas, increasing the
amount of 3a over 8 mol% and 10 mol%, neither the reaction
rate nor the yield was enhanced (Table 2, entries 5 and 6).
The operating reaction temperature was also assessed and
optimized. The best temperature was demonstrated to be 60 ꢀC
(Table 3, entry 2). An elevation of the operating temperature (70
ꢀC) did not demonstrate further improvement of the yield of 6a
(Table 3, entry 3). While, on employing the reaction at room
temperature, the desirable product (6a) was acquired in
moderate yield (Table 3, entry 1). Next, to evaluate any
benecial/detrimental impact of solvents on the [DABCO-DIOL]
[OAc] (3a) catalyzed substituted imidazole formation, the
template reaction (Scheme 2) was employed in protic polar,
aprotic polar, halogenated hydrocarbon, hydrocarbon solvents
and ethereal (Table 3, entries 3–10). As showed in Table 3, water
is obviously the best choice, as well as EtOH, for this reaction.
While the yield of 6a diminished drastically with other solvents,
denoting the detrimental inuence of these solvents.
Moreover, in order to study the inuence of the power of
ultrasonic intensity, the model reaction (Scheme 2) was
employed at 100%, 80%, 60%, 40% and 20% of the power rate of
the ultrasonic bath (200, 160, 120, 80 and 40 W). The outcomes
are outlined in Table 5. The ultrasonic intensity is directly
proportionate to the vibration amplitude of the ultrasound
exporter and, as such, a rise in the vibration amplitude will
result in a rise in both the vibration intensity and the sono-
chemical inuences. As outlined in Table 5, increasing the
intensity of the power up to 80% affords excellent yield in short
reaction time; beyond this value, the yield diminishes some-
what. Next, the same template reaction (Scheme 2) was also
performed using benzoin (5b) instead of benzil. The desirable
product was obtained in acceptable yield (96%) but in a longer
reaction time (15 min), indicating benzil is more convenient,
affording the required product (6a) in shorter reaction time with
higher yield.
Following these examinations, the best outcome was
ꢀ
acquired at 60 C, using 5 mol% of 3a as promoting catalyst,
which yielded the desirable product (6a) in 99% on sonication
for 5 min. In order to assess the scope and efficiency of this
protocol and to represent pharmacologically pertinent substi-
tution designs; diverse examples clarifying the current meth-
odology for the construction of 2,4,5-trisubstituted imidazole
derivatives 6a–p was investigated. The results are summed up in
Table 6. These outcomes manifested that the electronic inu-
ence of the substituents on the aldehydes had almost no impact
on the yield and the reaction rate: that is, the reactions are
equally activated with both electron-withdrawing and electron-
donating substituents on the aldehyde moieties. Additionally,
the current methodology has been utilized successfully for both
The impact of the nitrogen sources was also investigated by
performing the model reaction (Scheme 2) using different
ammonium salts (Table 4) instead of NH4OAc and the optimum
outcome was acquired with NH4OAc (Table 4, entry 2) as the
most effective nitrogen source.
Table 3 The influence of solvents and temperature on preparation of
6aa
Entry
Solvent
Temperature (ꢀC)
Yield (%)
1
2
3
4
5
6
7
8
9
10
H2O
H2O
H2O
Non
EtOH
DCM
MeCN
THF
Dioxane
Toluene
25
60
70
80
40
60
60
60
60
60
68
99
99
82
95
21
26
33
Table 5 Influence of US intensity power on the assembly of 6aa
Entry
Power intensity (%)
Watt (W)
Time (min)
Yield (%)
1
2
3
4
5
20
40
60
80
100
40
80
120
160
200
25
20
10
5
83
88
93
99
96
15
Trace
7
a
The mixture of 4a (1 mmol), 5a (1 mmol), NH4OAc (2.5 mmol) and 3a
(5 mol%) in solvent (5 mL) was sonicated for 5 min at different
temperatures.
a
The mixture of 4a (1 mmol), 5a (1 mmol), NH4OAc (2.5 mmol) and 3a
(5 mol%) in water (5 mL) was sonicated at 60 ꢀC.
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Table 6 Synthesis of 2,4,5-trisubstituted imidazoles (6a–p) via the reaction of benzil (5a), aldehydes (4a–p) and NH4OAc catalyzed by 3aa
mp
Entry
Ar
Time (min)
Yield (%)
Found
Reported
1
2
3
4
5
6
7
8
C6H5
5
4
4
7
6
6
8
8
5
5
7
6
7
5
5
6
99
99
98
97
95
98
95
96
98
98
97
96
96
99
98
99
272–273
230–232
234–236
255–227
202–204
214–216
230–232
260–262
265–266
192–193
263–265
171–173
242–243
255–257
201–202
244–246
272–274 (ref. 18)
229–231 (ref. 18)
232–234 (ref. 18)
255–256 (ref. 18)
201–203 (ref. 18)
213–216 (ref. 19)
226–227 (ref. 18)
262–264 (ref. 20)
261–263 (ref. 21)
199–201 (ref. 21)
262–263 (ref. 22)
172–173 (ref. 20)
239–242 (ref. 21)
254–256 (ref. 18)
201–203 (ref. 21)
243–245 (ref. 23)
4-CH3O–C6H4
4-HO–C6H4
4-Me2N–C6H4
2-HO–C6H4
3,4-(MeO)2C6H3
4-CH3–C6H4
4-F–C6H4
4-Br–C6H4
2-Cl–C6H4
4-Cl–C6H4
2,4-Cl2C6H3
4-NO2–C6H4
2-Thienyl
9
10
11
12
13
14
15
16
2-Furyl
CH3
a
The mixture of 4a–p (1 mmol), 5a (1 mmol), NH4OAc (2.5 mmol) and 3a (5 mol%) in water (5 mL) was sonicated at 60 ꢀC.
heteroaromatic and aliphatic aldehydes, and desired imidazole
derivatives were acquired in considerable yields (Table 6, component cyclo-condensation assembly of imidazoles (6a–p)
entries 14–16). promoted us to investigate the efficiency of catalyst 3a for the
The promising results obtained in case of the three-
Table 7 Preparation of 1,2,4,5-tetrasubstituted imidazoles (8a–j) via the reaction of benzil (5a), aldehydes (4a–f), amines (7a–e) and NH4OAc
catalyzed by 3aa
mp
Entry
Ar
Ar0
Time (min)
Yield (%)
Found
Reported
1
2
3
4
5
6
7
8
9
C6H5
C6H5
C6H5
C6H5
C6H5
5
7
5
6
7
5
5
5
6
6
98
96
96
95
96
98
98
98
96
96
220–222
188–189
183–185
161–162
209–211
160–164
150–153
132–135
158–161
152–154
219–221 (ref. 18)
185–187 (ref. 18)
183–185 (ref. 18)
160–163 (ref. 24)
207–211 (ref. 18)
160–164 (ref. 24)
150–154 (ref. 24)
132–135 (ref. 24)
158–162 (ref. 24)
152–154 (ref. 24)
4-CH3–C6H4
4-CH3O–C6H4
4-Cl–C6H4
4-Br–C6H4
C6H5
C6H5
C6H4–CH2
4-CH3O–C6H4–CH2
4-CH3–C6H4–CH2
4-F–C6H4–CH2
4-CH3O–C6H4–CH2
C6H5
4-CH3–C6H4
4-F–C6H4
4-CH3O–C6H4
10
a
The mixture of 4a–f (1 mmol), 7a–e (1 mmol), 5a (1 mmol), NH4OAc (1 mmol) and 3a (5 mol%) in water (5 mL) was sonicated at 60 ꢀC.
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Table 8 Comparison of reaction yields and times for the assembly of derivative 6a under different methodologies
Entry
Method
Catalyst
Time (min)
Yield (%)
Yield economy
1
2
3
4
5
6
7
8
US – 60 ꢀ
Grinding
Heating
Heating
C
3a
I2
NH4OAc
5
99 (present)
42 (ref. 25)
71 (ref. 26)
93 (ref. 27)
82 (ref. 28)
65 (ref. 29)
92 (ref. 30)
96 (ref. 31)
19.8
1.40
0.197
1.69
1.02
16.25
6.13
3.20
30
360
55
80
4
Phosphomolybdic acid
Heating – 65 ꢀC
MW
CANa
b
[HeMIM]BF4
HBF4–SiO2
Cu(NO3)2–zeolite
Heating – 120 ꢀC
Heating – 80 ꢀC
15
30
a
CAN: ceric ammonium nitrate. b [HeMIM]BF4: 1-methyl-3-heptylimidazolium tetrauoroborate.
construction of 1,2,4,5-tetrasubstituted imidazoles (8a–j) via the applicability of the current protocol, the same reaction condi-
four component reaction comprising 4a–f (1 mmol), 5a (1 tions were applied for the construction of the bis-2,4,5-
mmol), NH4OAc (1 mmol) and amines 7a–e (1 mmol) (Table 7). trisubstituted imidazoles (10a–f) via a similar one-pot, 3-MCR
The corresponding 1,2,4,5-tetrasubstituted imidazoles (8a–j) condensation of benzil (2 mmol), dialdehydes (9a–f) (1 mmol),
were acquired in excellent yields without the isolation of any by- and NH4OAc (4.5 mmol) as outline in Scheme 3 and the four
products like the generation of 2,4,5-trisubstituted imidazoles, component reaction (4-MCR) comprising benzil (2 mmol), dia-
oxidized products of aldehydes and anilines that are commonly ldehydes (9a–f) (1 mmol), aniline (2 mmol) and NH4OAc (2
obtained under the impact of strong acids.
mmol) to form bis-1,2,4,5-tetrasubstituted imidazoles (11a–f) as
A comparative study of the current methodology with the displayed in Scheme 4. The reaction was completed within
reported protocols for the assembly of 6a is compiled in Table 8, 7 min, and considerable yields of products were obtained
to show the efficiency and the merit of the current work. As (z95%). The structures of hitherto unreported derivatives (10b,
shown in Table 8, using of 3a is obviously the best choice for 10c, 10e, 10f and 11a–f) were interpreted from their IR, NMR
this reaction that could be used for the construction of a series and MS (see ESI†).
of multisubstituted imidazoles under ultrasonic conditions
with respect to reaction time and yield of the products.
A reasonable mechanism for the preparation of multi-
substituted imidazoles mediated by the [DABCO-DOL][OAc]
All the prepared derivatives (6 and 8) were conrmed by IR, catalyst is displayed in Scheme 5. The hydroxyl groups of 3a
NMR, and MS and also by comparing their spectral data with probably induce the polarization of the carbonyl groups in both
those of authentic samples. In order to explore more of the aldehyde and benzil under sonication. The catalyst stimulates
Scheme 3 Synthesis of bis-2,4,5-trisubstituted imidazoles 10a–f.
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Scheme 4 Synthesis of bis-1,2,4,5-tetrasubstituted imidazoles 11a–f.
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Scheme 5 Plausible mechanism for the catalytic synthesis of 2,4,5-
trisubstituted imidazoles (6) over [DABCO-DOL][OAc].
Scheme 6 Scaled-up syntheses of derivatives 6a, 8a, 10a and 11a.
reactions without any considerable diminish in reaction yields
(Fig. 1).
the aldehydic carbonyl group, in the presence of NH3, to form
the non-isolable intermediate 12 (hydroxylamine) that is dehy-
drated to imine 13. Nucleophilic attack of another NH3 mole-
cule yields intermediate 14, which attacks the activated
carbonyl group of benzil 5a, affording 15. Intermediate 15
undergoes dehydration reaction forming 16. Intramolecular
nucleophilic attack on 16 leads to the cyclization of 17. Subse-
quently, dehydration of 17 affords the trisubstituted imidazole
In order to demonstrate the potential for scale-up of the
protocol, the MCR was performed on the gram scale under the
optimal conditions, which in turn afforded the required prod-
ucts (6a, 8a, 10a and 11a) in quantitative yields (99, 99, 99 and
97%, respectively, Scheme 6).
product 6 with the recovery of 3a. The suggested mechanism Conclusion
may be belongs to the “on water” class,32 where water molecules
In the current work, an environmentally benign, efficient,
at the organic–aqueous interface has OH group that acts as
catalytic site for the reaction. These OH groups could be acted
as both acceptors and hydrogen-bond donors, and thence they
are partaken in trans-phase hydrogen bonding with the transi-
tion state that diminishes the reaction activation energy.17,33
Recyclability is another favorably merit of the catalyst under
investigation. Aer accomplishment of the reaction, the
product obtained was ltered off and washed with deionized
water. By removal of the water, the retrieved catalyst was washed
with ethyl acetate and reused for seven consecutive runs of
straightforward and atom-economic green protocol for prepa-
ration of structurally diverse mono- and bis-multisubstituted
imidazoles using renewable [DABCO-DOL][OAc] as promoter
under sonication was described. Compared to the traditional
methods, the current procedure can avert the utilization of
harmful organic solvents and extremely enhances the reaction
rate and thereby the excellent yields of the reactions that would
greatly participate to the manufacturing of drugs. This meth-
odology is bestowed with several unique merits including an
easy work up, simple experimental process and no side reac-
tions. Moreover, the catalyst can be facilely recycled and reused
at least seven runs with negligible loss of its activity or alter in
the structure, consequently, considerably contributes to the
practice of green chemistry.
Experimental
Chemical reagents in high purity were obtained commercially
and were used without further purication. Melting points were
determined in open capillaries using an Electrothermal IA9100
melting point apparatus (UK). 1H and 13C NMR spectra were
recorded using a Bruker UltraShield spectrometer at 400 and
100 MHz, respectively. High resolution mass spectra (HRMS)
Fig. 1 Recyclability of 3a in the preparation of 6a.
were performed utilizing a Bruker Daltonics microTOF
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spectrometer. FT-IR spectra were obtained with potassium
bromide pellets in the range of 400–4000 cmꢁ1 using a Perkin-
Elmer Spectrum One spectrometer. Ultrasonication was done in
a SY5200DH-T ultrasound cleaner.
Acknowledgements
I am very thankful to the Department of Organic Chemistry,
Arrhenius Lab., Stockholm University for providing laboratory
facilities.
Synthesis of the catalysts [DABCO-DOL][X] (3a–c)
A mixture of 1,4-diazobicyclo[2.2.2]octane (DABCO) (0.224 g, 2
mmol) and 2-chloro-1,3-propandiol (0.22 g, 2 mmol) in EtOH
(15 mL) was sonicated for 3 h (TLC). Then, the solvent was
removed under reduced pressure to afford compound (2). Then,
NaOAc (0.164 g, 2 mmol), KPF6 (0.368 g, 2 mmol) and/or NaBF4
(0.22 g, 2 mmol) was appended to the residue 2 (0.444 g, 2
mmol) in EtOH (20 mL). The resulting solution was sonicated
for 2 h and then, the solvent was evaporated in vacuo to afford
the corresponding ILs (3a–c) in quantitative yields.
Notes and references
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General procedure for the preparation of imidazoles 6a–p and
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A 25 mL Erlenmeyer ask was charged with aldehydes, 4a–p, (1
mmol) and/or dialdehyde, 9a–f, (0.5 mmol), benzil (1 mmol in
case of 4a–p, and 2 mmol in case of 9a–f), NH4OAc (2.5 mmol in
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surface of solution is slightly lower than the water level, the
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for appropriated time. Aer completion of reaction (conrmed
by TLC, eluent: MeOH/DCM ¼ 1 : 4 vol), the solid that separated
out was ltered washed with H2O, dried and recrystallized from
a proper solvent to afford the analytically pure product. The
catalyst was recovered from the aqueous layer under vacuum,
washed with ethyl acetate and reused for the next reactions. All
known products were conrmed by comparing their melting
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´
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A 25 mL Erlenmeyer ask was charged with aldehydes (4a–f, 1
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completion of reaction (conrmed by TLC, eluent: MeOH/DCM
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Conflicts of interest
There are no conicts to declare.
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