An extremely efficient and green method for the acylation of secondary alcohols, phenols and naphthols with a deep eutectic solvent as the catalyst

Article abstract of DOI:10.1039/c6ra22757k

The typical deep eutectic solvent [CholineCl][ZnCl₂]₃, easily prepared from choline chloride and zinc chloride, is green and useful for the acylation of secondary alcohols, phenols, and naphthols with acid anhydrides. Its efficiency allows the acylation of sterically hindered secondary alcohols and acid anhydrides to proceed in high yield under mild condition. The catalyst is cheap, easy to handle, conveniently synthesized in a single step, and recyclable for several times without significant loss of catalytic activity.

Full text of DOI:10.1039/c6ra22757k

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An extremely efficient and green method for the acylation of
secondary alcohols, phenols and naphthols with deep eutectic
solvent as catalyst
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Hai Truong Nguyen and Phuong Hoang Tran*
www.rsc.org/
2 3
The typical deep eutectic solvent [CholineCl][ZnCl ] easily prepared solvent such as acetonitrile is required. Consequently, they are
from choline chloride and zinc chloride is green and useful for the
acylation of secondary alcohols, phenols, and naphthols with acid
anhydrides. Its efficiency allows the acylation of sterically hindered
secondary alcohols and acid anhydrides to proceed in high yield
under mild condition. The catalyst is cheap, easy to handle,
conveniently synthesized in a single step, and recyclable for several
times without significant loss of the catalytic activity.
not convenient to apply on a large scale. Bartoli and co-
workers reported the use of Mg(ClO and Zn(ClO .6H O as
the better alternatives to metal triflates. This research showed
that the Zn(ClO .6H O is able to act as a powerful catalyst
4
)
2
4
)
2
2
4
)
2
2
16
which can be potentially applied in industrial processes.
However, this catalyst cannot be recovered and reused after
the aqueous work-up. Recently, Li and co-workers developed
DMAP saccharin-catalysed acylation of alcohols with an almost
equimolar amount of anhydrides under solvent-free and base-
1
7
free conditions. More recently, Collado and co-workers
reported the uses of titanium(III) species as a reductant for O-
The acylation of alcohols with acid anhydrides is a valuable
tool in the synthesis of biologically active compounds and
1
8
1
-3
acylation of alcohols and phenol. Although these methods
are efficient, many of them involve high-cost catalyst, large
amounts of volatile organic solvents and/or long reaction
times.
pharmaceutical products.
This reaction is commonly
catalysed by acid or base catalysts which are only efficient for
4
highly reactive primary alcohols. Although there have been
-6
7
-10
advances in acylation methods,
highly efficient, low-cost
and green catalysts are still in strong demand for the acylation
of sterically-hindered secondary alcohols and phenols. Up to
now, 4-(dimethylamino)pyridine (DMAP) has been the most
widely used nucleophile base catalyst for the acylation of
sterically-hindered alcohols even though it is known to have
The development of green and sustainable chemistry has led
to the search for an efficient and environmentally benign
1
9
catalyst. The deep eutectic solvents which are composed of
two or three components to form an eutectic mixture with
lower melting point than individual components were first
1
1
acute toxicity. Other catalysts that have been shown to be
efficient for acylation of sterically-hindered alcohols are metal
2
0
prepared by Abbott’s group in 2001. Up to now, they have
been used as catalysts for many organic transformations
1
triflates, such as scandium triflate, trimethylsilyl triflate,
2
13
2
1-25
1
4
15
including C-C, C-O, C-N bonding formation.
Deep eutectic
indium triflate, bismuth triflate. Amongst these, scandium
triflate and bismuth triflate demonstrated highly catalytic
activity. However, these catalysts required the use of donor
solvents such as dichloromethane, THF, or acetonitrile and the
excess of acid anhydrides (3-5 equiv.). Furthermore, despite
being classified as strong, efficient and stable Lewis acidic
catalysts, metal triflates are expensive, and the recycling of
catalyst involving the recrystallization from the toxic organic
solvents possessing the excellent catalytic activity and stability
can be comfortably handle due to low toxic, non-corrosive
properties. Moreover, these catalyst are easily recovered and
2
6
reused without the significant loss of reactivity.
Consequently, deep eutectic solvents are suitable for industrial
2
7-32
applications.
In our previous work, we found the Friedel–Crafts acylation of
aromatic compounds proceeded smoothly in the presence of
2
CholineCl][ZnCl2]3 as dual solvent–catalyst. Herein, we
5
[
report that [CholineCl][ZnCl2]3 demonstrates efficient catalytic
activity for the acylation of sterically-hindered secondary
alcohols and phenols under mild condition. Until now, its use
as a catalyst for acylation of alcohols and phenols has
remained unreported. The Lewis acidity of [CholineCl][ZnCl ] is
2
3
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robust enough to promote the acylation of sterically-hindered reaction time to 180 min produced 80% yield under the present
secondary alcohols to afford the acylated products in quantitative method. As previously reported, the acylation of alcohols
2 3
yields. Moreover, [CholineCl][ZnCl ] is easily prepared, stable to air proceeded with complete retention of configuration at the
1
0, 13, 15, 18
and moisture, low-cost, and recyclable without loss of catalytic hydroxyl-bearing carbon.
activity.
Table 2 The solvent-free acylation of 1-phenyletanol with acid
The results listed in Table 1 demonstrate the powerfully catalytic anhydrides at room temperature.
a
activity of [CholineCl][ZnCl
2
]
3
in the propionylation of 1-
Entry
Acid anhydride
Yield (%)
phenyletanol at room temperature for 30 min under solvent-free
condition. The reactions were carried out with propionic anhydride
1
2
3
Acetic anhydride
Propionic anhydride
Butyric anhydride
Benzoic anhydride
81
96
86
55
(
1.05 equiv.) in the presence of 35 mol% of the catalyst. The
propionylation of sterically-hindered 1-phenyletanol did not
proceed in the presence of traditional Brønsted acid (Table 1, entry
4
a
Isolated yield
2
). Bismuth triflate was not reactive under the present method
(
Table 1, entry 3). As previously reported, bismuth triflate-catalyzed
acylation of 1-phenyletanol proceeded quantitatively but required
the excess of acylating reagent (10 equiv) and took a longer
After these preliminary results, the propionylation of secondary
alcohols and phenols was conducted in the presence of 35 mol% of
15
reaction time (2 h). The excellent yield was noted under catalytic
influence of [CholineCl][ZnCl ] (Table 1, entry 10). The reaction was
[
2 3
CholineCl][ZnCl ] at room temperature (Table 3). The aliphatic
2
3
acyclic secondary alcohols containing 3–7 carbon atoms,
cyclohexanol, and menthol were propionylated in excellent yields,
and no olefin was detected (Table 3, entries 1-7). The
also carried out on a 10 mmol scale, and the yield is almost the
same as on 1 mmol scale (94% vs 96%, entry 10). The control
experiments were investigated by employing individual
[
CholineCl][ZnCl
2
]
3
-catalysed
propionylation
of
isoborneol
components such as choline chloride (entry 4) or ZnCl (entry 5).
2
proceeded smoothly at room temperature for only 30 min under
solvent-free (Table 3, entry 8). The use of bismuth triflate, in this
case, was reported with co-solvent (THF or toluene) and with longer
ZnCl displayed good catalytic activity but it cannot be recovered
2
after aqueous workup. The search for other deep eutectic solvents
was conducted but the lower yields of products (Table 1, entries 6-
3
3
reaction time (3 h to 7 h). In addition, no side-product was
detected under the present method. Moreover, it is noteworthy
that the desired products obtained after the workup attained the
sufficient purity for NMR analysis without further purification.
Remarkably, the propionylation of diphenylmethanol bearing more
sterically hindered substituents afforded the desired benzhydryl
propionate in 83% yield along with 17% yield of dibenzhydryl ether
as a side product (Table 3, entry 10). In the previous report, only
9
) were noted in comparison with [CholineCl][ZnCl ] .
2 3
Table 1 The solvent-free propionylation of 1-phenyletanol with
propionic anhydride at room temperature.
3
4
moderate yield was obtained for the same reaction. Per-O-
acylation is one of the most useful techniques for the protection of
a
35
Entry
Catalyst
None
Yield (%)
hydroxyl groups in carbohydrates. In the current method, per-O-
1
2
3
4
5
6
7
8
9
0
0
propionylation of α-D-glucose with the stoichiometric quantity
H
2
SO
Bi(OTf)
Choline chloride
ZnCl
[CholineCl][urea]
4
of propionic anhydride afforded in excellent yield (Table 3,
entry 11). As previously reported, a similar yield was obtained
in the presence of pyridine derivative and excess of acylating
b
3
7
6
1
7
2
80
0
reagent or organic solvent. Myo-inositol and phosphorylated
myo-inositol derivatives are useful precursors which play an
important role in calcium mobilization, insulin stimulation,
2
[CholineCl][Malonic acid]
[CholineCl][Oxalic acid]
7
3
6
38
5
exocytosis,
cytoskeletal
regulation.
Myo-inositol
was
[Urea]
7
[ZnCl
2
]
2
propionylated in 95% isolated yield of the per-O-propionylated
product at room temperature for 120 min. Phenols and naphthols
were also reactive under the current method (Table 3, entries 13-
15). Tertiary alcohols were unreactive under any investigated
conditions (Table 3, entries 16, 17). As reported by Procopiou, no
c
1
0
[CholineCl][ZnCl
b
2
]
3
96 (94)
c
was used. 10
a
Isolated yield. 10 mol% of Bi(OTf)
mmol scale reaction.
3
Under the optimal condition, the scope of acylating reagents was acetylation of tertiary alcohols by acetic anhydride was observed in
investigated by treating 1-phenyletanol with acetic, butyric and the presence of TMSOTf as a catalyst. The reaction only proceeded
1
3
benzoic anhydride in the presence of 35 mol% of in a slow rate with the addition of DMAP. It has also been known
CholineCl][ZnCl ] . The desired products were obtained in good to that 1,1-diphenyletanol was not acetylated by acetic anhydride in
[
2
3
1
6
excellent yields at room temperature for 30 min (Table 2, entries 1- the presence of Zn(ClO ) .6H O
4
.
2
2
3
). The benzoic anhydride afforded the lowest yield due to its least
reactivity (Table 2, entry 4). The benzoylation of 1-phenyletanol
taken place for 30 min afforded only 55% yield while prolonging the
2
| J. Name., 2012, 00, 1-3
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Table 3 The solvent-free propionylation of secondary alcohols (1.00 mmol), propionic
anhydride
(1.05
mmol),
and phenols at room temperature. [CholineCl][ZnCl ] (0.35 mmol) at room temperature for 30 min.
2 3
Yields are isolated yields after aqueous workup.
2 3
In conclusion, we have developed [CholineCl][ZnCl ] as a
a
Entry
Substrate
Time
min)
Yield
(%)
88
89
91
89
94
92
89
93
96
recyclable and highly efficient catalyst for the acylation of sterically-
hindered alcohols and phenols. This is the first time that the
acylation of secondary alcohols and phenols using deep
eutectic solvent as a catalyst has been reported. Moreover, the
present method demonstrates several merits, including a cheap and
highly stable catalyst, mild reaction conditions, operational
simplicity and no need for volatile organic solvents or inert
(
1
2
3
4
5
6
7
8
9
Propan-2-ol
Butan-2-ol
30
35
Pentan-2-ol
Hexan-2-ol
30
40
Heptan-2-ol
Cyclohexanol
Menthol
40
45
atmosphere condition. The fact that [CholineCl][ZnCl ] can be
2 3
30
easily prepared from commercially available cheap reactants makes
it more favorable than formerly investigated catalysts for acylation
of alcohols such as DMAP or metal triflates (2–10 mol%) even
though an uncommon large catalytic quantity of DES (35 mol%) was
required for a complete conversion. Besides, the high efficiency of
Isoborneol
30
1-Phenyletanol
Diphenylmetanol
60
b
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
60
83
c
α-D
-Glucose
100
120
60
94
d
myo-Inositol
95
[CholineCl][ZnCl ] allows for the acylation of poorly reactive
2 3
4-Methoxyphenol
[1,1’-Biphenyl]-2-ol
2-Naphthol
95
90
92
secondary alcohols under milder condition. Even a challenging
substrate for acylation as diphenylmethanol can be also
propionylated in good yield at room temperature. Moreover,
100
110
150
150
e
2-Phenylpropan-2-ol
1,1-Diphenylethanol
trace
the [CholineCl][ZnCl ] is efficient, easily recovered and reused
2 3
e
1
a
trace
without significant loss of catalytic activity for four consecutive
cycles, making it ideal for industrial processes.
Isolated yield.
b
c
Side product is (oxybis(methanetriyl))tetrabenzene.
per-O-propionylated in the presence of a stoichiometric
Acknowledgements
quantity of propionic anhydride (5 mmol).
d
per-O-propionylated in the presence of a stoichiometric
This research is funded by Vietnam National University-Ho Chi
Minh City (VNU – HCM) under grant number C2016-18-21. We
thank Duy-Khiem Nguyen Chau (University of Minnesota –
Duluth, USA) and Ngoc-Mai Hoang Do (IPH-HCM, Vietnam) for
their helps.
quantity of propionic anhydride (6 mmol).
e
The major alkene products were obtained by the
dehydration of tertiary alcohols.
Notes and references
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2 3
] was investigated under
optimized condition by using 1-phenyletanol as substrate (Scheme
3
7
1
). After completion of the reaction, the crude product was 1. H. K. Moon, G. H. Sung, B. R. Kim, J. K. Park, Y.-J. Yoon and H.
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Scheme
1 Recycling ability of [CholineCl][ZnCl2]3 in the
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propionylation of 1-phenyletanol. Conditions: 1-phenyletanol
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An efficient and green method was developed for the acylation of secondary alcohols, phenols and
naphthols using deep eutectic solvent [CholineCl][ZnCl ] as a catalyst at room temperature under
2
3
solvent-free condition.