Synthesis of Substituted Aryl Ketones by Addition of Alcohols to Alkynes Using Amberlyst-15/Ionic Liquid as a Recyclable Catalytic System

Article abstract of DOI:10.1055/s-0034-1380142

A highly efficient protocol for the synthesis of substituted aryl ketones by using Amberlyst-15 immobilized in [Bmim][PF₆] ionic liquid has been firstly developed. The present protocol works under metal-free, solvent-free, mild reaction conditions with 100% atom efficiency. The various aryl ketones were obtained in good to excellent yields. The developed catalytic system was recycled efficiently up to five cycles without significant loss in catalytic activity.

Full text of DOI:10.1055/s-0034-1380142

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 759–764
letter
759
K. V. Wagh, B. M. Bhanage
Letter
Synlett
Synthesis of Substituted Aryl Ketones by Addition of Alcohols to
Alkynes Using Amberlyst-15/Ionic Liquid as a Recyclable Catalytic
System
Kishor V. Wagh
R2
R2
O
H
Bhalchandra M. Bhanage*
Amberlyst-15
OH
R1
R1
R3
R3
+
Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai-400 019, India
bm.bhanage@gmail.com
[Bmim] [PF6]
4 h, 80 °C
64–76% yield
bm.bhanage@ictmumbai.edu.in
R1 = H, Me, OMe,
Cl, Br
R2 = Ph, Me
R3 = H, Me, OMe
NMe2
METAL FREE !
ADDITIVE FREE !
SOLVENT FREE !
Received: 29.11.2014
Accepted after revision: 14.01.2015
Published online: 12.02.2015
ing an efficient protocol for the synthesis of substituted aryl
ketones remains highly desirable. In this regard, synthesis
of substituted aryl ketones from alcohols and alkynes has
received considerable attention due to its atom economy
and ready availability of starting compounds. Recently, Jana
et al. have reported the synthesis of aryl ketones from ben-
zyl alcohols and alkynes using FeCl3·6H2O as catalyst in ni-
tromethane7 and Cook et al. have also reported the synthe-
sis of aryl ketones using FeCl3 and AgSbF6 catalysts in di-
chloroethane.8
DOI: 10.1055/s-0034-1380142; Art ID: st-2014-d0985-l
Abstract A highly efficient protocol for the synthesis of substituted
aryl ketones by using Amberlyst-15 immobilized in [Bmim][PF6] ionic
liquid has been firstly developed. The present protocol works under
metal-free, solvent-free, mild reaction conditions with 100% atom effi-
ciency. The various aryl ketones were obtained in good to excellent
yields. The developed catalytic system was recycled efficiently up to
five cycles without significant loss in catalytic activity.
Nowadays, green and recyclable reaction media such as
ionic liquids, glycerol, and PEG are often used in various or-
ganic transformations.9 Ionic liquids (IL) have been widely
used as green solvents due to their particular properties,
such as extremely low vapor pressure, high compatibility
with catalysts, and good thermal and chemical stability.10
Thus, these features of IL offer advantages such as simple
workup, recycling of the catalyst, and absence of organic
solvent. In particular IL have been found to favor certain
catalytic systems by stabilizing polar intermediates.11 In ad-
dition to this, IL also act to improve the activity and selec-
tivity of reactions.12
Thus, in continuation of our interest in application of IL
in various chemical transformations,13 we report herein the
synthesis of substituted aryl ketones from alcohols and
alkynes by using an Amberlyst-15/[Bmim][PF6] (1-butyl-3-
methylimidazolium hexafluorophosphate) catalytic system
(Scheme 1).
Key words heterogeneous catalysis, ionic liquid, addition reaction,
aryl ketone, atom economy
Aryl ketones have great importance in natural products,
pharmaceutical compounds, bioactive compounds, fra-
grance, dyes, agrochemicals.1 To date, various approaches
have been reported for the synthesis of aryl ketones.1 Com-
monly aryl ketones are synthesized by hydration of
alkynes.2 However, hydration of alkynes leads to the forma-
tion of mixture of ketones.3,2c Subsequently, a few indirect
methods have also been developed including microwave-
assisted regioselective hydration of internal alkynes using
PTSA4 and a one-pot synthesis of aryl ketones via a Sono-
gashira acid-mediated hydration strategy.5 Nevertheless,
these are multistep protocols and require the prior synthe-
sis of the internal alkyne precursors. In addition, prepara-
tion of internal alkynes requires the use of transition met-
als and functionalized starting materials.6 Hence, develop-
R2
O
R2
Amberlyst-15
[Bmim] [PF6]
OH
R1
R3
R1
+
H
R3
Scheme 1 Addition of alcohols to alkynes
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

760
K. V. Wagh, B. M. Bhanage
Letter
Synlett
In the initial study, the addition of benzhydrol (1a) to
phenylacetylene (2a) was chosen as a model reaction to op-
timize the reaction conditions. Reaction parameters such as
reagent loading, solvent, reactant ratio, reaction time, and
temperature were investigated for the model reaction (Ta-
ble 1). Firstly, different acidic reagents such as montmoril-
Table 1 Optimization for Addition of 1a with 2aa
OH
O
+ H
–
lonite K-10, p-toluene sulfonic acid, [NMP]+HSO4 ,
1a
2a
3a
–
[HMIM]+HSO4 , and Amberlyst-15 were studied (Table 1,
entries 1–5). It was observed that amongst the acids
screened, Amberlyst-15 was the most effective, providing
the desired product 3a in 45% yield (Table 1, entry 5). A pos-
sible reason for its higher activity may lie in physical prop-
erties such as high H+ exchange capacity (4.2 meq/g) and
surface area (42 m2/g).13d Next, we studied the effect of var-
ious solvents on the reaction (Table 1, entries 6–10) where
DCE was found to be an effective solvent providing 3a in
45% yield (Table 1, entry 5). Furthermore, when the reac-
tion was performed in ionic liquids such as [Bmim][BF4]
and [Bmim][PF6] as a reaction media, it provided 3a in 52%
and 58% yield, respectively (Table 1, entries 11 and 12). As
[Bmim][PF6] provided higher yield of 3a, it was used for fur-
ther studies. Subsequently, we have also studied the effect
of Amberlyst-15 concentration on the reaction yield, and it
was observed that yield of 3a decreases with decreasing the
reagent concentration from five equivalents to three equiv-
alents (Table 1, entries 13 and 14). The substrate ratio of
1a/2a was also examined, and it was observed that a ratio
of 1.2:1 was the optimum for this reaction (Table 1, entries
15 and 16). Subsequently, the effect of reaction time and
temperature were also investigated for the synthesis of 3a,
it was observed that four hours was the minimum time re-
quired for the completion of this reaction (Table 1, entries
17 and 18).
Entry
Reagent
Solvent
Time Temp Yield
(h)
(°C)
(%)b
1c
2d
Montmorillonite K-10
PTSA
DCE
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
8
6
4
4
4
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
70
80
21
14
38
32
45
24
30
32
10
39
52
58
71
64
76
80
80
80
75
DCE
3d
[NMP]+HSO4
DCE
–
4d
[HMIM]+HSO4
DCE
–
5
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
Amberlyst-15
–
DCE
6
toluene
7
dioxane
8
cyclohexane
MeCN
9
10
11
12
13e
14f
15e,g
16e,h
17e,h
18e,h
19e,h
20
CHCl3
[Bmim][BF4]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
[Bmim][PF6]
n.d.
During temperature studies, it was found that 80 °C was
optimum reaction temperature, as a decrease in tempera-
ture decreased the yield of 3a (Table 1, entry 19). Impor-
tantly, when the reaction was performed in the absence of
reagent, formation of 3a was not observed (Table 1, entry
20). Hence, the optimized reaction conditions for the syn-
thesis of 3a are as follows: 1a (1.2 mmol), 2a (1.0 mmol),
Amberlyst-15 (5 equiv), [Bmim][PF6] IL (2 mL), 80 °C, 4 h.15
With these optimized reaction conditions in hand, the
scope of the developed protocol was examined for the syn-
thesis of various substituted 1,3,3-triphenylpropan-1-one
derivatives (Table 2). The reaction of 1a with 2a provided
the desired 1,3,3-triphenylpropan-1-one (3a) in 75% yield
(Table 2, entry 1).
It was found that reaction of 1a with aromatic alkynes
having electron-donating (Me, OMe, NMe2) substituents on
the aromatic ring furnished the corresponding compounds
3b–d in good yields (Table 2, entries 2–4). Furthermore, re-
action of 1a with aliphatic alkyne 2a was also well tolerated
and provided the corresponding product 3e in 64% yield
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), reagent (3 equiv), sol-
vent (2 mL).
b GC yield; n.d. = not detected.
c Conditions: reagent 7.5 equiv.
d Conditions: reagent 2 equiv.
e Conditions: reagent 5 equiv.
f Conditions: reagent 4 equiv.
g Ratio of 1a/2a = 1.1:1.
h Ratio of 1a/2a = 1.2:1.
(Table 2, entry 5). Next, we studied the reaction of various
benzhyrol derivatives with 2a. It was found that 1a bearing
an electron-donating group (OMe) gave the expected prod-
uct 3f in 76% yield (Table 2, entry 6). Furthermore, it was
observed that sterically hindered o-methylbenzhydrol (1c)
also reacted efficiently providing the corresponding 1,3-di-
phenyl-3-(o-tolyl)propan-1-one (3g) in 70% yield (Table 2,
entry 7). Equally, 1a bearing a halo substituent furnished
the corresponding product 3h in 71% yield (Table 2, entry
8). Next, 1-phenylethanol and derivatives with electron-do-
nating (Me, OMe) and halo (Cl, Br) substituents, also pro-
vided the corresponding products 3i–m in good yields (Ta-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

761
K. V. Wagh, B. M. Bhanage
Letter
Synlett
ble 2, entries 9–13). However, benzylic and aliphatic alco-
hols did not provide the desired products under the
optimized reaction conditions (Table 2, entries 14 and 15).
In order to render the developed protocol more effi-
ciently, the recyclability of this catalytic system was studied
for the model reaction for five cycles. This Amberlyst-
15/[Bmim][PF6] proved to be effective for the five cycles in
this study, respectively, without significant loss in activity
(80%, 78%, 77%, 75%, and 74%).
Table 2 Substrate Study for Addition of Alcohols to Alkynesa
Entry
Alcohol
Alkyne
Product
Yield (%)b
OH
O
O
O
H
1
75
2a
1a
1a
3a
H
2
76
2b
3b
OMe
H
3
1a
75
3c
OMe
3c
O
NMe2
H
4
5
6
1a
70
64
76
2d
NMe2
3d
O
H
1a
2e
3e
OH
O
2a
MeO
1b
MeO
3f
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

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K. V. Wagh, B. M. Bhanage
Letter
Synlett
Table 2 (continued)
Entry
Alcohol
Alkyne
Product
Yield (%)b
OH
O
7
2a
70
1c
3g
OH
O
8
2a
71
Cl
1d
Cl
3h
OH
O
9
2a
65
68
1e
1f
3i
3j
OH
O
10
2a
2a
2a
OH
O
11
12
70
70
MeO
1g
MeO
3k
OH
O
O
Cl
1h
Cl
3l
OH
13
14
15
2a
2a
2a
65
Br
3m
Br
1i
O
OH
n.d.
n.d.
1j
3n
3o
OH
O
1k
a Reaction conditions: alcohol (1.2 mmol), alkyne (1.0 mmol), Amberlyst-15 (5 equiv), 80 °C, 4 h.
b Isolated yield; n.d. = not detected.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

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K. V. Wagh, B. M. Bhanage
Letter
Synlett
H+
H
H2O
OH
2
+
R1
R2
path B
R1
R2
1
6
OH
H2O
R1
R2
H
1
+
H+
path A
R2
R1
R2
H2O
R1
H+
R1
O
R2
O
R1
R2
OH
H+
4
R1
R2
1
Scheme 2 Plausible mechanism for addition of alcohol and alkynea
Based on our experimental observations and literature
precedent7,13a we proposed the following tentative mecha-
nism (Scheme 2). It has been observed that the alcohol 1 is
rapidly converted into self-coupled dimeric ether 4 in the
presence of an acidic catalyst (path A) and intermediate 4
was isolated and characterized by GC–MS. Subsequently,
the dimeric ether 4 is activated in the presence of Am-
berlyst-15/[Bmim][PF6] catalytic system and generates in-
termediate carbocation 5 that is stabilized in the polar ionic
liquid. The ionic liquid [Bmim][PF6] also serves to enhance
the acidity of Amberlyst-15.13f Next, the nucleophilic attack
of alkyne 2 onto intermediate carbocation 5 leads to the
formation of alkenyl cation 6. Finally, addition of water onto
the alkenyl cation 6, followed by deprotonation and tau-
tomerism provides desired product 3.
We have also performed a control experiment by react-
ing intermediate 4 with 2 under the optimized reaction
conditions and observed that this reaction provided 3 in
good yield. However, an alternative pathway cannot be
ruled out which involves the generation of carbocation 5
from the benzylic alcohol 1 in the presence of Amberlyst-
15/[Bmim][PF6] catalytic system (path B), followed by elec-
trophilic addition of alkyne to 5 providing the correspond-
ing alkenyl cation 6, which undergoes deprotonation and
tautomerism to 3.
Acknowledgment
K.V.W. is grateful to the University Grant Commission, India for pro-
viding a Senior Research Fellowship.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380142.
S
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p
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References and Notes
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In conclusion, we have developed a simple, novel, and
efficient methodology for the synthesis of substituted aryl
ketones by using an Amberlyst-15/[Bmim][PF6] catalytic
system. This is the first metal- and solvent-free protocol
providing a range of aryl ketones in good yields with short
reaction times. The present catalytic system has greater
substrate compatibility and can be reused for five consecu-
tive cycles without much significant loss in activity.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

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K. V. Wagh, B. M. Bhanage
Letter
Synlett
Zh. Obsch. Khim. 1959, 29, 3153. (e) Tani, K.; Kataoka, Y. In Cata-
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hols with Alkynes
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To a well-stirred mixture of Amberlyst-15 [H+ exchange capac-
ity (4.2 meq/g) and high surface area (42 m2/g)] (5 equiv) in
[Bmim][PF6] (2 mL), 1a (1.2 mmol) and 2a (1 mmol) were
added. The reaction mixture was stirred at 80 °C, and the prog-
ress of the reaction was monitored by GC/TLC. After completion
of reaction, the mixture was cooled to r.t., and diisopropyl ether
(5 mL) was added with vigorous shaking. The ether phase was
separated, and the extraction procedure was repeated (3 × 5
mL). The organic extracts were combined, dried over anhydrous
Na2SO4, filtered, and evaporated under reduced pressure. The
residue was purified by column chromatography [silica gel, 60–
120 mesh; PE–EtOAc (9:1)] to give 1,3,3-triphenylpropan-1-one
(3a) in 75% yield. After extraction, the reaction vessel contain-
ing the recovered Amberlyst-15/[Bmim][PF6] was dried in vacuo
for an hour and then charged with 1a and 2a directly for the
next run. The various ionic liquids used were prepared as previ-
ously reported.14
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1,3,3-Triphenylpropan-1-one (3a)
White solid; yield: 213 mg (75%). 1H NMR (400 MHz, CDCl3): δ =
7.98–7.96 (m, 2 H), 7.58–7.56 (m, 1 H), 7.49–7.45 (m, 2 H),
7.31–7.28 (m, 8 H), 7.23–7.18 (m, 2 H), 4.87 (t, J = 8 Hz, 1 H),
3.78 (d, J = 8 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 198.01,
144.17, 137.11, 128.61, 128.57, 128.07, 127.86, 126.39, 45.97,
44.76. GC–MS (EI): m/z = 286 (10.5) [M+], 167 (31.3), 165 (15.5),
155 (28.0), 105 (100.0), 77 (28.3), 71 (10.5), 43 (11.4).
3,3-Diphenyl-1-p-tolylpropan-1-one (3b)
(12) (a) Chauvin, Y.; Mussmann, L.; Olivier, H. Angew. Chem. 1995,
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(b) Qureshi, Z. S.; Deshmukh, K. M.; Bhor, M. D. Bhanage B. M.
Catal. Commun. 2009, 10, 833. (c) Deshmukh, K. M.; Qureshi, Z.
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(d) Qureshi, Z. S.; Deshmukh, K. M.; Tambade, P. J.; Dhake, K. P.;
Bhanage, B. M. Eur. J. Org. Chem. 2010, 6233. (e) Qureshi, Z. S.;
Deshmukh, K. M.; Dhake, K. P.; Bhanage, B. M. RSC Adv. 2011, 1,
1106. (f) Qureshi, Z. S.; Deshmukh, K. M.; Tambade, P. J.; Dhake,
K. P.; Bhanage, B. M. Tetrahedron Lett. 2010, 51, 724.
White solid; yield: 228 mg (76%). 1H NMR (400 MHz, CDCl3): δ =
7.90–7.88 (m, 2 H), 7.31–7.26 (m, 7 H), 7.23–7.20 (m, 5 H), 4.87
(t, J = 8 Hz, 1 H), 3.76 (d, J = 8 Hz, 2 H), 2.44 (s, 3 H). 13C NMR
(100 MHz, CDCl3): δ = 197.63, 144.27, 143.88, 134.65, 129.29,
128.56, 128.22, 127.88, 126.36, 46.01, 44.62, 21.65. GC–MS (EI):
m/z = 300 (10.7) [M+], 167 (25.8), 165 (12.8), 120 (9.9), 119
(100.0), 91 (24.8), 77 (4.9).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 759–764

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