A remarkable HBF4-SiO2-catalyzed synthesis of acylals from aldehydes under solvent-free conditions

Article abstract of DOI:10.1055/s-2006-950282

HBF₄-SiO₂ has been found to be an outstanding catalyst for the protection of carbonyl compounds as acylals under entirely solvent-free conditions. Some of the major advantages of this procedure are high yields, ease of operation, high chemoselectivity, high atom efficiency, and compatibility with other protecting groups. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-950282

LETTER
2719
A Remarkable HBF -SiO -Catalyzed Synthesis of Acylals from Aldehydes
4
2
under Solvent-Free Conditions
a
a
a
b
H
a
V
BF
-
SiO-Cataly
i
zed Sy
n
nthesis of
A
c
o
ylals fromA
d
ldehydes T. Kamble,* Babasaheb P. Bandgar, Neeta S. Joshi, Vasant S. Jamode
4
2
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Nanded 431606, Maharashtra, India
Fax +91(2462)259465; E-mail: vtkd@rediffmail.com
Department of Chemistry, Amravati University, Amravati 444602, Maharashtra, India
b
Received 10 April 2006
hanced reaction rates, greater selectivity, simple workup
and recoverability of catalysts. Among the various
heterogeneous catalysts, particularly, silica-supported
reagents23 have advantage of low cost, ease of prepara-
Abstract: HBF -SiO has been found to be an outstanding catalyst
4
2
for the protection of carbonyl compounds as acylals under entirely
solvent-free conditions. Some of the major advantages of this pro-
cedure are high yields, ease of operation, high chemoselectivity,
high atom efficiency, and compatibility with other protecting tion, and catalyst recycling. Since the reaction is heteroge-
groups.
neous in nature, the catalyst can conveniently be separated
Key words: acylals, carbonyl compounds, chemoselective, HBF4– by simple filtration.
SiO , protection
2
In view of recent surge in the use of heterogeneous cata-
lysts, we wish to report a simple, convenient, and efficient
method for the preparation of acylals from aldehydes us-
ing silica-supported fluoroboric acid as an inexpensive
and eco-friendly catalyst (Scheme 1). The catalyst was
Protection and deprotection are important strategies that
continue to generate considerable interest in multi-step
synthetic organic chemistry. The protection of carbonyl
1
23e
prepared by using the known procedure. The present
groups is often necessary during the synthesis of many
method not only affords the products in excellent yields
but also avoids the problems associated with catalyst cost,
handling, safety and pollution. Enhanced reaction rates
and improved selectivity were obtained in the presence of
this catalyst.
2
biologically important compounds. Among the various
carbonyl protecting groups, the 1,1-diacetates are impor-
tant, owing to their stability in neutral and mild condi-
1
a,3
tions. Moreover, 1,1-diacetates have found variety of
4
applications in the synthesis of chiral allylic esters,
5
dienes, and as cross-linking reagents for cellulose in cot-
ton. In view of the practical need and synthetic utility of
6
Ac2O, HBF4–SiO2 (0.1 mol%)
RCHO
RCH(OAc)2
1
,1-diacetates, numerous methods have been developed
neat, r.t
1
2
for their synthesis. In general, 1,1-diacetates are synthe-
sized from aldehydes and acetic anhydride by employing
Scheme 1
7
8
9
protic acids, Lewis acids, heterogeneous catalysts, and
1
0
supported reagents. But these methods often suffer from
drawbacks like long reaction time, drastic conditions, low
product yields, stoichiometric amount of catalyst and use
of toxic solvents. More recently Lewis acids such as
In the first instance, we investigated the catalytic effect of
HBF -SiO on acylation reaction. After many studies on
4
2
the acylation of benzaldehyde (1 mmol) with acetic anhy-
dride (1 mmol) at room temperature, we found that when
less than 0.1 mol% of HBF -SiO was applied, lower
1
1
12
13
H P W O ·24H O,
ZrCl ,
Fe (SO ) ·xH O,
6
2
18 62
2
4
4
2
4 3
17
2
1
15
16
4
2
Bi(NO ) ·5H O, Cu(BF ) , InBr , KHSO , and met-
3
3
2
4 2
3
4
yields of the corresponding product (Table 1, entries 2-5)
resulted, whereas use of more than 0.1 mol% did not im-
prove the yield (Table 1, entries 7 and 8). When attempts
were made to carry out this reaction in the absence of
HBF -SiO the substrate was recovered almost quantita-
1
8
19
20
al triflates like Sc(OTf) , Cu(OTf)2, Bi(OTf)3, and
3
2
1
LiOTf, have been reported for this conversion. Unfortu-
nately, the main disadvantage of almost all of the afore-
said protocols is the requirement of acetic anhydride in
excess (1.5–8 equiv), which results in the generation of
significant quantities of waste. Thus, simple, efficient,
avoiding toxic solvents, site-selective and environmental-
ly benign methods are still desirable.
4
2,
tively (Table 1, entry 1).
Next, we studied the effect of various solvents and the re-
sults of the reaction of benzaldehyde (1 mmol) with acetic
anhydride (1 mmol) using HBF -SiO (0.1 mol%) in the
4
2
Over the last few years, there has been a considerable
growth in interest in the use of solid-supported reagents22
in organic synthesis because of their ease of handling, en-
presence of various solvents are shown in Table 2.
When organic solvents such as dichloromethane, nitro-
methane, acetonitrile, tetrahydrofuran, chloroform, were
used for this reaction, the desired product was obtained in
low yields (Table 2, entries 2–6). Whereas an excellent
yield of the desired product was obtained when the reac-
tion was carried out at room temperature under solvent-
SYNLETT 2006, No. 17, pp 2719–2722
1
7
.1
0
.2
0
0
6
Advanced online publication: 09.10.2006
DOI: 10.1055/s-2006-950282; Art ID: D10406ST
©
Georg Thieme Verlag Stuttgart · New York

2
720
V. T. Kamble et al.
LETTER
Table 1 A Catalytic Study of HBF –SiO During Acylation of
Benzaldehyde (1 mmol) with Acetic Anhydride (1 mmol) at Room
Temperature under Solvent-Free Conditions
Table 3 HBF –SiO -Catalyzed Acylation of Benzaldehyde with
Other Acid Anhydrides
4
2
4
2
a
Entry Aldehyde Anhydride (RCO) O Time (min) Yield (%)
2
Entry
HBF –SiO (mol%) Time (min)
Yield (%)
4
2
1
PhCHO
R = n-Pr
R = i-Pr
R = t-Bu
45
55
60
94
89
87
1
2
3
4
5
6
7
8
–
360
20
15
10
6
–
0.02
0.04
0.06
0.08
0.1
60
70
80
85
99
99
99
a
Yields are expressed from pure isolated products
ditions. It is worth noting that both naphthaldehydes
Table 3, entries 12 and 13) and anthraldehyde (Table 3,
(
entry 14) were also diacylated under similar conditions,
but the acylation of anthraldehyde required a longer reac-
tion time.
2
0.12
0.14
2
In view of a greener chemistry, efficient recovery and re-
use of the catalyst are highly desirable. In our procedure,
the catalyst was recovered conveniently and reused effi-
2
ciently without any activation. The reusability of HBF -
4
Table 2 Investigation of Various Solvents
SiO was examined by using benzaldehyde as a model
2
substrate and the results are described in typical experi-
mental procedure.
Entry
Solvent
–
Time (min)
Yield (%)
1
2
3
4
5
6
2
120
90
99
45
50
55
45
40
The catalytic activity of HBF -SiO is specific for the
4
2
CH Cl
aldehyde group and ketone groups of the starting material
remain unaltered in the protection process. For example,
for acetyl benzaldehyde the aldehyde group was convert-
ed to the corresponding diacetate while the ketone func-
tionality remained unaffected (Scheme 2). This result
suggests that the protocol is useful for carrying out similar
chemoselective reactions.
2
2
MeNO2
MeCN
THF
90
100
100
CHCl3
free conditions (Table 2, entry 1). These results led to the
suggestion that solvent-free conditions are best suited for
this reaction.
CHO
CH(OAc)2
Ac2O, HBF4–SiO2 (0.1 mol%)
neat, r.t., 20 min
Structurally diverse aldehydes were reacted with acetic
anhydride to give the corresponding acylals in excellent
yields. The reactions proceeded smoothly at room temper-
COCH3
COCH3
7%
9
ature under solvent-free conditions and were completed Scheme 2
within 1-15 minutes of reaction time. The results as sum-
marized in Table 3 clearly reveal the scope and generality
In order to generalize the catalytic efficiency of HBF -
4
of the protocol with respect to various aldehydes. The re-
actions proceeded quite cleanly without any side reactions
and diacylated products were obtained in 94-99% yields.
The tolerance of various functional groups under the
present reaction conditions have been examined by react-
ing the substrates with fluoro, chloro, methyl, methoxy,
and nitro groups (Table 3, entries 5–11), and the reaction
conditions are compatible with these functional groups.
Acid-sensitive substrates like furfuraldehyde, and
thiophene-2-carboxaldehyde (Table 3, entries 15 and 16)
are also diacylated by this procedure without any difficul-
SiO for other acylating agents, we employed benzalde-
2
hyde as a representative example during the reaction with
different acid anhydrides (Table 3). Acylation with propi-
onic, butyric and isobutyric anhydrides resulted in 87-
9
4% yields.
As compared to the recently reported methods10–20 that
require excess of acetic anhydride (1.5-8 equiv), the
present method required a stoichiometric amount of acetic
anhydride. Moreover, a small amount of HBF -SiO (0.1
mol%) is sufficient for the reaction to proceed cleanly.
4
2
ty. The reaction conditions are mild enough not to induce In conclusion, we have developed a simple, convenient
any isomerization for conjugated aldehydes (Table 3, and effective method for easy synthesis of acylals by the
entries 23 and 24). Protecting groups like O-tert- reaction of aldehydes with anhydrides using silica-sup-
butyldimethylsilyl, O-allyl, O-p-nitrobenzyl, O-benzyl, ported fluoroboric acid at room temperature under entire-
methylenedioxy, and NHBoc (Table 3, entries 17-22) ly solvent-free conditions. Present methodology offers
were smoothly diacylated under the present reaction con- very attractive features such as reduced reaction times,
Synlett 2006, No. 17, 2719–2722 © Thieme Stuttgart · New York

LETTER
HBF -SiO -Catalyzed Synthesis of Acylals from Aldehydes
2721
4
2
Table 4 HBF –SiO -Catalyzed Synthesis of Acylals
Preparation of Catalyst
4
2
HBF (1.65 g, as a 40% aq solution) was added to the suspension of
4
Entry Substrate
Time (min) Yield (%)a,b
silica gel (13.35 g, 230-400 mesh) in Et O (40 mL). The mixture
2
was concentrated and the residue was dried under vacuum at 100 °C
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
n-PrCHO
n-C H CHO
1
1
98
96
97
99
98
98
97
96
97
99
96
97
96
95
97
98
97
98
97
96
97
94
98
96
95
–c
–1
for 72 h to afford HBF –SiO (0.5 mmol g ) as a free-flowing pow-
4
2
der.
5
11
Synthesis of Acetoxyphenylmethyl Acetate; Typical Procedure
n-C H CHO
1
7
15
A mixture of benzaldehyde (5 mmol) and freshly distilled Ac O (5
2
PhCHO
4-FC H CHO
2
mmol) was stirred at r.t. in the presence of a catalytic amount of
HBF -SiO (10 mg, 0.005 mmol) for an appropriate time (Table 1).
4
2
2
6
4
After completion of the reaction, as indicated by TLC, reaction mix-
ture was directly distillated under reduced pressure to furnish pure
4-ClC H CHO
2
1
6
4
acetoxyphenylmethyl acetate (98%), identical (mp, IR, and
H
NMR) to an authentic sample. The catalyst (HBF –SiO ) that re-
4
2
4-MeC H CHO
2
6
4
mained in the distilling flask was used directly for the acylation of
fresh lot of benzaldehyde (5 mmol) affording 95% yield of acetoxy-
phenylmethyl acetate after 10 min. The recovered catalyst, without
activation, was reused for four more consecutive acylation reactions
of benzaldehyde (5 mmol) affording 92%, 90%, 86%, 84% yields in
4-CNC H CHO
2
6
4
9-MeOC H CHO
2
6
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
4-NO C H CHO
2
2
6
4
1
2 min, 15 min, 20 min, and 25 min, respectively.
3-NO C H CHO
3
Physical and spectral data of selected products from Table 4 are as
follows.
2
6
4
1-C H CHO
2
1
0
7
Entry 1
Oil.
2-C H CHO
2
1
0
7
IR (neat): 2950, 2875, 1750, 1245, 1220, 1075 cm-
1
9-C H CHO
15
5
1
4
9
1
H NMR (CDCl ): d = 0.95 (t, J = 4.0 Hz, 3 H), 1.40-1.45 (m, 2 H),
2-Furaldehyde
3
1
.75-1.80 (m, 2 H), 2.05 (s, 6 H), 6.85 (t, J = 5.5 Hz, 1 H).
Thiophene-2-carboxaldehyde
4-(OTBDMS)C H CHO
4
Entry 4
Mp 45 °C (Lit. mp 44–45 °C).
2
7b
6
4
-
1
IR (KBr): 1755, 1515, 1435, 1250, 1225, 1015 cm .
3-(O-Allyl)C H CHO
2
6
4
1
H NMR (CDCl ): d = 2.10 (s, 6 H), 7.40-7.45 (m, 3 H), 7.50–7.55
3
3-(OBz)C H CHO
2
6
4
(
m, 2 H), 7.70 (s, 1 H).
3-(OPNB)C H CHO
4
6
4
Entry 7
Mp 81 °C (Lit. 81-82 °C).
9
g
3,4-(OCH O)C H CHO
2
2
6
3
IR (KBr): 2950, 1765, 1710, 1525, 1400, 1245, 1210, 1015, 960,
4-NHBocC H CHO
3
6
4
-1
9
25 cm .
PhCH=CHCHO (E)
7
1
H NMR (CDCl ): d = 2.10 (s, 6 H), 2.40 (s, 3 H), 7.22 (d, J = 8.2
3
Hz, 2 H), 7.40 (d, J = 8.2 Hz, 2 H), 7.60 (s, 1 H).
CH CH=CHCHO (E)
2
3
Entry 14
Mp 202-203 °C (Lit. 204 °C).
CH =CHCHO
2
2
3
4-NMe C H CHO
600
IR (KBr): 3015, 2945, 1745, 1650, 1525, 1245, 1020, 930 cm-1.
2
6
4
a
b
c
1
Yields are of pure isolated products.
Products were characterized by their spectral analysis.
The starting material remained intact.
H NMR (CDCl ): d = 2.15 (s, 6 H), 7.35-7.50 (m, 4 H), 8.05 (d,
3
J = 8.2 Hz, 2 H), 8.42 (s, 1 H), 8.75 (d, J = 8.2 Hz, 2 H), 9.20 (s, 1 H).
Entry 23
Mp 84 °C (Lit. 84–86 °C).
3
-
1
IR (KBr): 3040, 2945, 1750, 1680, 1495, 1245, 1010, 975 cm .
higher yields, economic viability of the catalyst, and mild
nature of silica-supported fluoroboric acid when com-
pared with recently reported catalysts, which will have
wide scope in organic synthesis. The simple procedure
combined with ease of recovery and reuses of this catalyst
make this method economic, benign and a waste-free
chemical process for the synthesis of acylals.
1
H NMR (CDCl ): d = 2.12 (s, 6 H), 5.90 (dd, J = 7.0, 16.0 Hz, 1 H),
3
6
.80 (d, J = 16.0 Hz, 1 H), 7.20-7.40 (m, 6 H).
Synlett 2006, No. 17, 2719–2722 © Thieme Stuttgart · New York

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722
V. T. Kamble et al.
LETTER
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Synlett 2006, No. 17, 2719–2722 © Thieme Stuttgart · New York