Silica sulfuric acid and AI(HSO4)3: As efficient catalysts for the formylation of alcohols by using ethyl formate under heterogeneous conditions

Article abstract of DOI:10.1002/jccs.200800132

A mixture of ethyl formate and a catalytic amount of silica sulfuric acid or Al(HSO₄)₃ as suitable formylating systems can formylate various alcohols to their corresponding formate ester derivatives under mild, nearly neutral and heterogeneous conditions at room temperature with good to excellent yields.

Full text of DOI:10.1002/jccs.200800132

Journal of the Chinese Chemical Society, 2008, 55, 885-889
885
Silica Sulfuric Acid and Al(HSO4)3: As Efficient Catalysts for the
Formylation of Alcohols by Using Ethyl Formate under Heterogeneous
Conditions
Mohammad Ali Zolfigol,a* Gholamabbas Chehardoli,b Mina Dehghanian,a Khodabakhsh Niknam,c*
Farhad Shirinid and Ahmad Khoramabadi-Zada
aFaculty of Chemistry, Bu-Ali Sina University, Zip code 6517838683, Hamedan, Iran
bSchool of Pharmacy, Hamedan University of Medical Sciences, Zip Code 65178, Hamedan, Iran
cDepartment of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
dDepartment of Chemistry, College of Science, Guilan University, Rasht, Iran
A mixture of ethyl formate and a catalytic amount of silica sulfuric acid or Al(HSO4)3 as suitable
formylating systems can formylate various alcohols to their corresponding formate ester derivatives under
mild, nearly neutral and heterogeneous conditions at room temperature with good to excellent yields.
Keywords: Formylation; Silica sulfuric acid; Ethyl formate; Alcohols; Al(HSO4)3.
INTRODUCTION
In recent years, the search for environmentally be-
tives for very dangerous concentrated sulfuric acid, and
there are several reports about using these solid acids in or-
ganic transformation.
nign chemical processes or methodologies has received
much attention from chemists, because they are essential
for the conservation of the global ecosystem. The develop-
ment of heterogeneous catalysts for fine chemical synthesis
has become a major area of research, as the potential ad-
vantages of these materials (simplified recovery and reus-
ability and the potential for incorporation in continuous re-
actors and micro reactors) over homogeneous systems can
lead to novel environmentally benign chemical procedures
for academia and industry.1 From this viewpoint, catalytic
reaction is a valuable process because the use of stoichio-
metric reagents that are often toxic poses inherent limita-
tions from both economical and environmental viewpoints
regarding product purification and waste management.2
Application of solid acids in organic transformation
have an important role, because, solid acids have many ad-
vantages such as simplicity in handling, decreased reactor
and plant corrosion problems, and more environmentally
safe disposal. On the other hand, any reduction in the amount
of liquid acid needed and/or any simplification in handling
procedures is required for risk reduction, economic advan-
tage and environmental protection.3-10 Among solid acids,
silica sulfuric acid5 and Al(HSO4)36 are two nice alterna-
O-Formylation could be the method of choice for pro-
tecting an alcoholic group in a complex synthetic sequence
because deformylation can be affected selectively in the
presence of acetate or other ester protecting groups. Fur-
ther, if the alcoholic group is planned to be oxidized later in
the synthetic scheme, the formylated alcoholic group need
not be deprotected, and direct oxidation under Oppenauer
conditions can be realised.11-14 Although various formylat-
ing agents have been reported previously, there are still se-
rious limitations for the preparation of formates due to the
drastic reaction conditions, the use of uncommon reagents,
formation of undesirable or toxic by-products, the applica-
tion of expensive catalysts for preparation of formylating
agents and the thermal instability of the reagents.15 To the
best of our knowledge, one of the most common formylat-
ing agents is formic acid which is corrosive and toxic.
Meanwhile, acid sensitive functional groups may be de-
structed and side reactions increased in formylation reac-
tions by using formic acid.
RESULTS AND DISCUSSION
In continuation of our studies on the catalytic sys-
* Corresponding author. Tel/Fax: +98 (811) 8257407; E-mail: zolfi@basu.ac.ir and mzolfigol@yahoo.com (Mohammad Ali Zolfigol);
E-mail: niknam@pgu.ac.ir and khniknam@gmail.com (Khodabakhsh Niknam)

886 J. Chin. Chem. Soc., Vol. 55, No. 4, 2008
Zolfigol et al.
tems in organic transformation5-7 and formylation of
alcohols,16-18 we were interested to find a catalytic hetero-
geneous system for the formylation of alcohols under
nearly neutral conditions. Thus, for finding the best cata-
lytic reagent systems, we studied a good range of cata-
lysts for the formylation of alcohols using ethyl formate
as a neutral formylating agent (Scheme I). As shown in
Table 1, the best results are silica sulfuric acid (SSA) and/or
Al(HSO4)3/ethylformate systems (Table 1).
Table 1. Investigation of the ability of various catalysts for the
formylation of benzyl alcohol in ethyl formate under
ambient temperature
Catalyst
Catalyst/Substrate Time (min) Yields (%)a
Al(HSO4)3
Al(HSO4)3
Zr(HSO4)4
Fe(HSO4)3
Fe(HSO4)3
Ca(HSO4)2
Ca(HSO4)2
Mg(HSO4)2
NaHSO4
0.5
0.2
0.2
0.6
0.3
0.2
0.4
0.4
10
Immed.
60
20
25
30
60
50
30
90
75
Immed.
10
10
10
5
92
92
78
89
75
63
85
80
44
49
99
5
Scheme I
KHSO4
10
OH
O
Silica sulfuric acid
Poly-SO3H
H3PW12O40
WCl6
0.25 (g)
0.4 (g)
0.2
1
O
Catalyst
rt
O
H
+
EtO
H
94
10
17
92
95
60
10
13
19
--
Na2WO4.2H2O
ZrCl4
1
Results presented in Table 2 show that the obtained
result for ethyl formate as both solvent and reactant is
better than using ethyl formate as reactant in the other sol-
vents (Table 2).
0.4
0.6
1.5
2
5
AlCl3
5
MgCl2
15
15
10
5
CaCl2.2H2O
CeCl3.7H2O
Alanine
0.8
2
A good range of alcohols were subjected to formyl-
ation reaction in the presence of a catalytic amount of SSA
or Al(HSO4)3 in ethyl formate (3 mL) as an efficient for-
mylating system for the formylation of alcohols to their
corresponding formates under mild, nearly neutral and het-
erogeneous conditions (Table 3 and Scheme II).
DABCO
2
30
a GC yields
Table 2. Effect of various solvents on the transformylation of
benzyl alcohol with a catalytic amount of Al(HSO4)3b in
ethyl formate under ambient temperature
Yield (%)a
Scheme II
Entry
Solvent
Time (min)
1
2
3
4
5
6
7
7
--
Immed.
92
60
CH2Cl2
CHCl3
5
5
5
5
5
5
5
30
EtOAC
Acetone
n-Hexane
CH3CN
EtOH
30
48
85
36
Trace
a GC yields.
b 0.5 mmol.
The described catalytic systems are suitable for acid
sensitive and biologically important substrates such as 1k
(Scheme III).
Also the described catalytic formylating systems are
chemoselective so that formylation of alcohols did occur in
the presence of phenols selectively. To show this chemo-
selectivity, a competitive reaction was designed. A mixture
of equal amounts of n-octanol and phenol were subjected to

Formylation of Alcohols Catalyzed by SSA and Al(HSO4)3
J. Chin. Chem. Soc., Vol. 55, No. 4, 2008 887
Table 3. Formylation of alcohols using a catalytic amount of
silica sulfuric acid (I) or Al(HSO4)3 (II) in ethyl formate
(3 mL) at room temperature
Scheme III
Reagent/substrate
Substrate Product
Time (min) Yields (%)a
I (g) II (mmol)
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
2a
2a
2b
2b
2c
2c
2d
2d
2e
2e
2f
0.25
--
--
0.5
--
Immed.
99
92
99
96
99
99
92
90
90b
89b
90
94
85
86
90
92
99
93
99
95
43b
86b
97
96
99
98
Immed.
0.4
--
Immed.
0.6
--
5
Immed.
5
0.4
--
0.65
--
0.4
--
5
0.6
--
10
0.4
--
5
0.75
--
15
0.25
--
Immed.
5
1f
2f
0.5
--
1g
1g
1h
1h
1i
2g
2g
2h
2h
2i
0.25
--
25
0.55
--
20
0.25
--
10
0.5
--
5
0.25
--
20
addition to the existing methodologies.
1i
2i
0.55
--
16
1j
2j
0.3
--
25
1j
2j
0.55
--
15
EXPERIMENTAL SECTION
1k
1k
1l
2k
2k
2l
0.1
--
15
General
0.4
--
20
Chemicals were purchased from Fluka, Merck and
Aldrich chemical companies. The yields of all volatile for-
mylated products have been determined by GC. The for-
mylated products were characterized by comparison of
their spectral and physical data with authentic samples.16-20
Silica sulfuric acid (SSA) and Al(HSO4)3 were synthesized
according to our previously reported procedures.5,6
General procedure
0.375
--
20
1l
2l
0.5
--
15
1m
1m
2m
2m
0.25
--
10
0.55
16
a GC yields.
b Isolated yields.
formylation in the presence of a catalytic amount of the de-
scribed catalysts in a reaction vessel (Scheme IV).
Solid acid (I or II) was added to ethyl formate (3 mL)
and the mixture was stirred for several minutes. Then alco-
hol 1 (1 mmol) was added to the above mentioned mixture
and the suspension was stirred at room temperature for the
specified time (for molar ratio and time see Table 3). The
progress of the reaction was monitored by TLC or GC.
When the progress of reaction was fixed, the suspension
was filtered off and both water (10 mL) and CH2Cl2 (10
CONCLUSION
In conclusion, chemoselectivity, the cheapness and
availability of the reagents, nearly neutral and heteroge-
neous conditions, easy and clean work-up and high yields
make this method practical for multi-step synthesis. We be-
lieve that the present methodology could be an important
Scheme IV
Al(HSO )
4 3
or
Silica sulfuric acid
OH
O
O
O
OH
+
O
H
H
+
+
EtO
H
O
rt
0%
>95%

888 J. Chin. Chem. Soc., Vol. 55, No. 4, 2008
Zolfigol et al.
mL) were added to the filtrate. Organic phase was sepa-
rated and anhydrous Na2SO4 (3 g) was added to the filtrate
and filtered off after 20 min. The crude products were ob-
tained by the removing of solvent under mild conditions
(The products are sensitive to heat. Thus, the temperature
should be controlled).
2l:15 IR (KBr): 2987, 2985, 1750, 1485, 1135 cm-1. 1H
NMR (90 MHz, CDCl3): d (ppm) 1.4-1.8 (complex, 15H),
7.9 (s, 1H).
2m: bp 197-198/760 (°C), (Lit.20 198/760); IR (neat):
1
2985, 2930, 1720, 1470, 1165 cm-1. H NMR (90 MHz,
CDCl3): d (ppm) 1.2-1.5 (complex, 15H), 4.1 (t, 2H), 8.0
Spectral data
(s, 1H).
2a: bp 200/760 (°C), (Lit.20 201/760); IR (Nujol):
3060, 2930, 1659, 1598, 1277, 919, 700 cm-1. 1H NMR (90
MHz, CDCl3): d (ppm) 5.14 (s, 2H), 7.33 (s, 5H), 8.05 (s,
1H).
ACKNOWLEDGMENT
Financial support for this work by the Research Af-
fairs and Center of Excellence in Development of Chemi-
cal Methods (CEDCM) of Bu-Ali Sina University, Hamedan,
Iran, is gratefully acknowledged.
2b: colorless liquid;21 IR (Nujol): 3038, 2931, 1724,
1
1450 cm-1. H NMR (90 MHz, CDCl3): d (ppm) 5.10 (s,
2H), 7.30 (m, 4H), 8.13 (s, 1H).
2c: colorless liquid;22 IR (Nujol): 3040, 2960, 1725,
Received December 25, 2007.
1
1620, 1510, 1450 cm-1. H NMR (90 MHz, CDCl3): d
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