Highly efficient and chemoselective acetalization of carbonyl compounds catalyzed by new and reusab e zirconyl triflate, zr0(0tf)2

Article abstract of DOI:10.1002/hc.20523

Various types of aromatic aldehydes were efficiently converted to their corresponding 1,3-dioxanes and 1,3-dioxolane with 1,3-propanediol and ethylene glycol, respectively, in the presence of catalytic amount of ZrO(OTf) ₂ in acetonitrile at room temperature. The catalyst can be reused several times without loss of its catalytic activity. Very short reaction times, selective acetalization of aromatic aldehydes in the presence of aliphatic aldehydes and ketones, very mild reaction conditions, reusability of the catalyst, and easy workup are noteworthy advantages of this method.

Full text of DOI:10.1002/hc.20523

Heteroatom Chemistry
Volume 20, Number 3, 2009
Highly Efficient and Chemoselective
Acetalization of Carbonyl Compounds
Catalyzed by New and Reusable Zirconyl
Triflate, ZrO(OTf)
2
Majid Moghadam, Iraj Mohammadpoor-Baltork, Shahram
Tangestaninejad, Valiollah Mirkhani, Parvin Yazdani,
and Saeedeh Ghorjipoor
Department of Chemistry, Catalysis Division, University of Isfahan, Isfahan 81746-73441, Iran
Received 15 November 2008; revised 26 February 2009
are carried out by treatment of carbonyl compounds
ABSTRACT: Various types of aromatic aldehydes
with the alcohols, diols, or the corresponding ortho-
were efficiently converted to their corresponding 1,3-
formates in the presence of protic or Lewis acid cat-
dioxanes and 1,3-dioxolane with 1,3-propanediol and
alysts. Several methods have been reported for this
ethylene glycol, respectively, in the presence of cat-
transformation [1–19]. However, many of the acid
alytic amount of ZrO(OTf)2 in acetonitrile at room
catalysts, which have been explored for this trans-
temperature. The catalyst can be reused several times
formation, suffer from disadvantages such as toxic-
without loss of its catalytic activity. Very short reac-
ity, corrosiveness, and high cost of the catalyst, poor
tion times, selective acetalization of aromatic alde-
chemical selectivity, long reaction times, high tem-
hydes in the presence of aliphatic aldehydes and ke-
perature, and tedious workup procedure.
tones, very mild reaction conditions, reusability of
Zirconium(IV) salts have recently attracted
the catalyst, and easy workup are noteworthy advan-
much attention due to their low cost, high catalytic
ꢀ
C
tages of this method.
2009 Wiley Periodicals, Inc.
activity, easy availability, and low toxicity [20]. A
variety of Zr(IV) salts have been used for several
organic transformation such as the Friedel–Crafts
reaction [21], Diels–Alder reaction [22], Michael re-
action [23], acetalization of carbonyl compounds
[24,25], conversion of nitriles to oxazolines and imi-
dazolines [26,27], and some other reactions [28,29].
In this paper, we report a highly efficient
and chemoselective acetalization of carbonyl com-
pounds with 1,3-propanediol or ethylene glycol in
the presence of catalytic amounts of ZrO(OTf)2 in
acetonitrile at room temperature (Scheme 1).
Heteroatom Chem 20:131–135, 2009; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20523
INTRODUCTION
Acetalization is one of the most widely used meth-
ods for protection of aldehydes and ketones in syn-
thetic organic chemistry. Generally, these reactions
Correspondence to: Majid Moghadam; e-mail: moghadamm@
sci.ui.ac.ir.
Contract grant sponsor: Council Research of University of
Isfahan.
EXPERIMENTAL
Contract grant number: 861237.
Contract grant sponsor: Center of Excellence of Chemistry of
University of Isfahan (CECUI).
2009 Wiley Periodicals, Inc.
Chemicals were purchased from Fluka and Merck.
1H NMR spectra were recorded in CDCl3 solvent on
a Bruker AM 80 MHz or a Bruker AC 500 MHz
c
ꢀ
131

132 Moghadam et al.
TABLE 1 Acetalization of 4-Bromobenzaldehyde with 1,3-
Propanediol and in the Presence of Zirconium Salts at Room
Temperaturea
O
O
R
R′
O
ZrO(OTf)2
CH3CN
OH
OH
OH
+
Yield (%)b
or
or
R'
R
Entry
ZrCl4
ZrOCl2
ZrO(OTf)2
Time (min)
O
R
O
HO
1
2
3
4
0
0
0
0
0
0
10
26
89
93
94
1
2
3
4
R′
SCHEME 1
100
aReaction conditions: aldehyde (1 mmol), diol (3 mmol), catalyst
spectrometer using TMS as an internal standard.
Infrared spectra (IR) were run on a Philips PU9716
or Shimadzu IR-435 spectrophotometer. All analyses
were performed on a Shimadzu GC-16A instrument
with a flame ionization detector using silicon DC-200
or Carbowax 20M columns. ZrO(OTf)2 was prepared
according to the reported procedure [30].
(1 ml%), and CH3CN (2 mL).
bGC yield.
ature and the corresponding acetals were obtained
in good to excellent yields (entries 1–13 in Table 2).
Aliphatic aldehydes bearing aromatic ring in the α-
or β-position are also protected with high yields (en-
tries 14 and 15 in Table 2).
However, aliphatic aldehydes without aromatic
rings, cinammaldehyde, and ketones were less reac-
tive under these conditions and the corresponding
acetals were obtained in very low yields (entries 16–
20 in Table 2). On the basis of the obtained results, it
seems that this protocol can be used for the selective
acetalization of aromatic aldehydes in the presence
of aliphatic aldehydes (without aromatic ring) and
ketones. In this respect, we found that in the reaction
of an equimolar mixture of 4-bromobenzaldehyde
with 1,3-propanediol in the presence of acetophe-
none or heptanal, 4-bromobenzaldehyde was con-
verted to 2-(4-bromophenyl)-1,3-dioxane with high
degree of chemoselectivity and acetophenone and
heptanal remained intact in the reaction mixture
(Scheme 2). As there are only a few reports on the
selective acetalization of aromatic aldehydes in the
presence of aliphatic aldehydes or ketones, there-
fore, the present acetalization method catalyzed by
ZrO(OTf)2 can be considered as a useful practical
achievement in protection reactions. Blank exper-
iments showed that under similar reaction condi-
tions and in the absence of ZrO(OTf)2, no acetal was
observed in the reaction mixture.
General Procedure for the Acetalization
of Aldehydes or Ketones
To a solution of aldehyde or ketone (1 mmol) in
CH3CN (2 mL), 1,3-propanediol or ethylene glycol
(3 mmol) and ZrO(OTf)2 (4 mg, 0.01 mmol) were
added and the mixture was stirred at room temper-
ature. The reaction progress was monitored by GC.
After completion of the reaction, cold aqueous so-
lution of NaOH (5%, 15 mL, for neutralization
of media to prevent the deprotection of product)
was added and the mixture was extracted with
Et2O (3 × 10 mL). The organic solution was dried
(MgSO4). The filtrates were concentrated and chro-
matographed on a silica gel column to give the pure
product.
RESULTS AND DISCUSSION
Acetalization of Carbonyl Compounds in the
Presence of ZrO(OTf)2
First, we investigated the ability of different zir-
conium salts such as ZrCl4, ZrOCl2 · 8H2O, and
ZrO(OTf)2 in the acetalization of 4-bromoenz-
aldehyde with 1,3-propanediol in CH3CN as sol-
vent at room temperature. As shown in Table 1,
ZrO(OTf)2 is superior in terms of reaction time and
product yield. In comparison with acetonitrile, the
reaction times were longer and the yields were lower
when dichloromethane (75%, 30 min), chloroform
(55%, 30 min), and n-hexane (15%, 30 min) were em-
ployed as solvents. Under the optimized conditions,
various types of aromatic aldehydes were subjected
to acetalization with 1,3-propanediol or ethylene gly-
col (3 mmol) in the presence of catalytic amount of
ZrO(OTf)2 (1 mol%) in dry CH3CN at room temper-
Catalyst Reusability
The recovery and reusability of the catalyst was
investigated in the acetalization of 4-bromobenz-
aldehyde with 1,3-propanediol. After each reaction,
the solvent was evaporated, Et2O (10 mL) was added
and filtered. The recovered catalyst was washed with
Et2O (10 mL) and used in another acetalization re-
action. The results showed the catalyst can be used
for five consecutive times without any decrease in its
catalytic activity.
Heteroatom Chemistry DOI 10.1002/hc

Efficient and Chemoselective Acetalization of Carbonyl Compounds Catalyzed by New and Reusable Zirconyl Triflate 133
TABLE 2 Acetalization of Carbonyl Compounds with 1,3-Propanediol and Ethylene Glycol Catalyzed by ZrO(OTf)2a
Row
1
Aldehyde
Product
Time (min) Yield (%)b
Product
Time (min) Yield (%)b
O
O
H
O
O
O
4
2
100
96
6
4
100
100
Br
Br
Br
O
O
H
2
O
O
O
O2N
O2N
O2N
O
H
O
O
3
4
2
3
95
94
2
3
81
O
O
Cl
Cl
Cl
H
O
O
O
O
O
100
O2N
O2N
O2N
O
O
H
5
2
90
5
89
O
O
O
NO2
NO2
NO2
O
O
O
O
H
O
6
7
3
1
89
86
3
2
92
80
Cl
Cl
Cl
H
O
O
Cl
Cl
Cl
Cl
Cl
O
O
O
O
O
O
O
H
O
Cl
8
2
85
2
81
Cl
Cl
Cl
H
O
O
9
1
1
1
80
75
69
3
5
2
60
81
58
O
O
O
MeO
F
MeO
MeO
H
O
O
O
O
O
10
11
F
F
O
H
O
H3C
H3C
H3C
O
O
O
O
O
O
O
H
O
12
3
63
1
73
OMe
OMe
OMe
(Continued)
Heteroatom Chemistry DOI 10.1002/hc

134 Moghadam et al.
TABLE 2 Continued
Row
13
Aldehyde
Product
Time (min) Yield (%)b
Product
Time (min) Yield (%)b
O
O
O
O
H
O
2
63
2
65
MeO
MeO
MeO
O
O
O
14
15
16
H
4
100
2
97
O
O
CH3
CH3
CH3
O
O
O
4
2
88
8
4
1
91
57
O
O
H
H
O
O
O
O
O
O
O
O
O
17
18
19
3
3
2
16
10
27
2
4
4
20
12
31
H3C
O
O
H
H3C
H3C
O
O
CH3(CH2)5
CH3(CH2)5
CH3(CH2)5
H
O
O
O
O
O
O
O
O
O
Me
O
20
4
10
1
12
CH3
Me
O
O
aReaction conditions: carbonyl compound (1 mmol), diol (3 mmol), ZrO(OTf)2 (1 ml%), and CH3CN (2 mL).
bGC yields.
O
H
O
Br
Br
100%
0%
OH
OH
O
O
O
ZrO(OTf)2, CH3CN
O
H
O
O
89%
3%
H
O
OH
ZrO(OTf)2, CH3CN
OH
Cl
Cl
O
O
O
CH3
Me
SCHEME 2
Heteroatom Chemistry DOI 10.1002/hc

Efficient and Chemoselective Acetalization of Carbonyl Compounds Catalyzed by New and Reusable Zirconyl Triflate 135
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CONCLUSION
In conclusion, an efficient method has been de-
veloped for the selective acetalization of aromatic
aldehydes in the presence of aliphatic aldehydes
and ketones in the presence of catalytic amounts of
ZrO(OTf)2. Very short reaction times, easy workup,
very mild reaction conditions, and high to excellent
yields make this method a useful addition to the
existing methodologies for the acetalization of car-
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Heteroatom Chemistry DOI 10.1002/hc