Acetylation and formylation of alcohols in the presence of silica sulfuric acid

Article abstract of DOI:10.1080/10426500307877

Alcohols are converted to esters in a mild, clean, and efficient reaction with acetic and formic acids in the presence of silica sulfuric acid. All reactions were performed under mild and completely heterogeneous conditions in refluxing n-hexane.

Full text of DOI:10.1080/10426500307877

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Phosphorus, Sulfur, and Silicon and the Related
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Acetylation and Formylation of Alcohols in the
Presence of Silica Sulfuric Acid
Farhad Shirini a , Mohammad Ali Zolfigol b & Kamal Mohammadi a
a Guilan University, Rasht, Iran
b Bu-Ali Sina University, Hamadan, Iran
Version of record first published: 27 Oct 2010.
To cite this article: Farhad Shirini , Mohammad Ali Zolfigol & Kamal Mohammadi (2003): Acetylation and Formylation of
Alcohols in the Presence of Silica Sulfuric Acid, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:7, 1617-1621
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Phosphorus, Sulfur, and Silicon, 178:1617–1621, 2003
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390213022
ACETYLATION AND FORMYLATION OF ALCOHOLS
IN THE PRESENCE OF SILICA SULFURIC ACID
Farhad Shirini,a Mohammad Ali Zolfigol,b
and Kamal Mohammadia
Guilan University, Rasht, Iran;a and Bu-Ali Sina University,
Hamadan, Iranb
(Received February 4, 2002)
Alcohols are converted to esters in a mild, clean, and efficient reac-
tion with acetic and formic acids in the presence of silica sulfuric acid.
All reactions were performed under mild and completely heterogeneous
conditions in refluxing n-hexane.
Keywords: Acetylation; alcohols; formylation; heterogeneous condi-
tions; silica sulfuric acid
During the multistep synthesis of natural products, the efficiency of
the synthetic protocol employed often depends largely on protection
and deprotection of the functional groups involved. To this end, pro-
tecting groups have been playing a crucial role during the synthesis
of complex natural products.1 Among the various protecting groups
used for hydroxyl function, acetyl is the most common group because
of its easy introduction, stability to acidic reaction conditions, and ease
of its removal by mild alkaline hydrolysis. Acetylation2 is most com-
monly performed using,3,4 reagents such as Ac2O or AcCl in the pres-
ence of base procedures which are not environmentally friendly. The
use of HOAc/mineral acid for acetylation suffer from the problem of re-
10
versability. Later modifications involving the use of Lewis acids,5
in
combination with Ac2O, is inherently wasteful since half of every acid
anhydride molecule is lost as a carboxylic acid and the use of HOAc (as
13
solvent)-lanthanate trifilates,11
while efficient, is expensive.
Formylation is
a very important process in organic chem-
istry. Although various formylation reagents have been reported
We are thankful to the Guilan University Research Council for partial support of this
work.
Address correspondence to Farhad Shirini, Department of Chemistry, Faculty of
Science, Guilan University, Rasht, Iran. E-mail: shirini@cd.gu.ac.ir
1617

1618
F. Shirini et al.
previously,14–24 there are still serious 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 application
of expensive catalysts for preparation of formylating agents and ther-
mal instability of the reagents.
On the other hand, any reduction in the amount of sulfuric acid
needed and/or any simplification in handling procedures are required
for risk reduction, economic advantage, and environment protection.25
In addition, there is current research and general interest in heteroge-
neous systems because of the importance such systems have in industry
and in developing technologies.26 In continuation of our studies on the
application of inorganic acidic salts,27 we found that silica gel reacts
with chlorosulfonic acid to give silica sulfuric acid (I). It is interesting
to note that the reaction is easy and clean without any work-up proce-
dure because HCl gas is evolved from the reaction vessel immediately
(Scheme 1).
SCHEME 1
We hoped that silica sulfuric acid (I) would be a superior proton
source to all of the reported acidic solid supports or acidic resin such as
polystyrene sulfonic acid and Nafion-H28 for running reactions under
heterogeneous conditions. Herein we report a mild, simple, and efficient
method for the acetylation and formylation of alcohols with acetic and
formic acids in the presence of silica sulfuric acid (Scheme 2).
SCHEME 2
As shown in Table I, this method can be used as an efficient method
for acetylation and formylation of primary, allylic, benzylic, hindered,
and unhindered secondary and sterically hindered tertiary alcohols. All
reactions were performed under mild and completely heterogeneous
conditions in n-hexane at reflux temperature and products were ob-
tained in good to high yields.
In conclusion, we have developed an efficient method for the acetyla-
tion and formylation of alcohols with acetic and formic acids under mild

Acetylation and Formylation of Alcohols
1619
TABLE I Acetylation and Formylation of Alcohols
Entry
Substrate
Product
Time (min) Yield%a,b
1
2
3
4
5
6
7
8
9
2-ClC6H4CH2 OH
4-ClC6H4CH2 OH
2-BrC6H4CH2 OH
2-MeC6H4CH2 OH
4-MeOC6H4CH2 OH
4-(Me)3CC6H4CH2 OH
3-NO2C6H4CH2 OH
C6H5CH(OH)C6H5
C6H5CH2CH2CH2OH
C6H5CH2CH(OH)CH3
C6H5CH(CH3)CH2 OH
C6H5CH2CH2 OH
1-Methylcyclohexanol
Cyclohexanol
2-ClC6H4CH2 OAc
4-ClC6H4CH2 OAc
2-BrC6H4CH2 OAc
2-MeC6H4CH2 OAc
4-MeOC6H4CH2 OAc
4-(Me)3CC6H4CH2 OAc
3-NO2C6H4CH2 OAc
C6H5CH(OAc)C6H5
C6H5CH2CH2CH2 OAc
C6H5CH2CH(OAc)CH3
C6H5CH(CH3)CH2 OAc
C6H5CH2CH2 OAc
10
10
35
5
10
10
60
5
45
60
40
20
60
50
50
50
10
10
30
5
10
10
60
5
55
15
50
30
75
60
35
40
86
90
83
85
80
85
90
93
85
84
90
95
85
80
82
80
90
85
80
85
90
85
83
92
87
85
85
90
95
90
85
90
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
1-Methylcyclohexyl acetate
Cyclohexyl acetate
tert.Butyl acetate
tert.Butyl alcohol
C6H5CH CHCH2 OH
2-ClC6H4CH2 OH
4-ClC6H4CH2 OH
2-BrC6H4CH2 OH
2-MeC6H4CH2 OH
4-MeOC6H4CH2 OH
4-(Me)3CC6H4CH2 OH
3-NO2C6CH4CH2 OH
C6H5CH(OH)C6H5
C6H5CH2CH2CH2 OH
C6H5CH2CH(OH)CH3
C6H5CH(CH3)CH2 OH
C6H5CH2CH2 OH
1-Methylcyclohexanol
Cyclohexanol
C6H5CH CHCH2 OAc
2-ClC6H4CH2 OC(O)H
4-ClC6H4CH2 OC(O)H
2-BrC6H4CH2 OC(O)H
2-MeC6H4CH2 OC(O)H
4-MeOC6H4CH2 OC(O)H
4-(Me)3CC6H4CH2 OC(O)H
3-NO2C6H4CH2 OC(O)H
C6H5CH[OC(O)H]C6H5
C6H5CH2CH2CH2 OC(O)H
C6H5CH2CH[OC(O)H]CH3
C6H5CH(CH3)CH2 OC(O)H
C6H5CH2CH2 OC(O)H
1-Methylcyclohexyl formate
Cyclohexyl formate
tert.Butyl alcohol
C6H5CH CHCH2 OH
tert.Butyl formate
C6H5CH CHCH2 OC(O)H
aProducts were characterized by their physical constants, comparison with
authentic samples and IR and NMR spectroscopy.
b
Isolated yield.
reaction conditions. The reactions are clean and the products yields are
good to high and the procedure is easy.
Experimental Section
Preparation of Silica Sulfuric Acid
A 500 mL suction flask equipped with a constant-pressure dropping
funnel and a gas inlet tube for conducting HCl gas over an adsorbing
solution (i.e., water) was used. It was charged with silica gel (60.0 g).

1620
F. Shirini et al.
Chlorosulfonic acid (23.3 g, 0.2 mmol) was added dropwise over a pe-
riod of 30 min at room temperature. HCl gas evolved from the reaction
vessel immediately (Scheme 1). After the addition was complete the
mixture was shaken 30 min. A white solid (silica sulfuric acid, 76.0 g)
was obtained.
General Procedure for Acetylation and Formylation of Alcohols in the
Presence of Silica Sulfuric Acid. A mixture of the substrate (1 mmol),
acid (1 mmol), and silica sulfuric acid (0.05 g) in n-hexane (3 mL) was
refluxed for the specified time (Table I). The reaction was monitored by
TLC or GC. After completion of the reaction, the mixture was filtered
and the solid residue was washed with dichloromethane (10 mL). Evap-
oration of the solvent followed by column chromatography on silica gel
gave the corresponding esters in good to high yields.
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