P-Toluenesulfonyl chloride as a new and effective catalyst for acetylation and formylation of hydroxyl compounds under mild conditions

Article abstract of DOI:10.1016/j.cclet.2010.05.025

The catalytic application of p-toluenesulfonyl chloride for efficient acetylation of various types of alcohols and phenols with acetic anhydride in solvent-free conditions is reported. Also structurally diverse alcohols were formylated using formic acid based on the use of catalytic amount of p-toluenesulfonyl chloride under solvent-free condition. The reactions were carried out in short reaction time and in good to excellent yields at room temperature.

Full text of DOI:10.1016/j.cclet.2010.05.025

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 1430–1434
www.elsevier.com/locate/cclet
p-Toluenesulfonyl chloride as a new and effective
catalyst for acetylation and formylation of hydroxyl
compounds under mild conditions
a,
Ardeshir Khazaei , Amin Rostami , Fatemeh Mantashlo
b,*
a
*
a
Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
b
Department of Chemistry, Faculty of Science, University of Kurdistan, Sanandaj 66135, Iran
Received 15 April 2010
Abstract
The catalytic application of p-toluenesulfonyl chloride for efficient acetylation of various types of alcohols and phenols with
acetic anhydride in solvent-free conditions is reported. Also structurally diverse alcohols were formylated using formic acid based
on the use of catalytic amount of p-toluenesulfonyl chloride under solvent-free condition. The reactions were carried out in short
reaction time and in good to excellent yields at room temperature.
#
2010 Ardeshir Khazaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: p-Toluenesulfonyl chloride; Hydroxyl compounds; Acetylation; Formylation
Among the various protecting groups used for the hydroxyl function, acetyl is the most common group because of
the ease of formation as well as mild conditions for deprotection [1,2]. In addition, the ester moiety is a common
functional group in polymers, drugs, and biologically relevant compounds. The most commonly used reagent
combination for this reaction is acid anhydride in the presence of acid or base catalysts [3–15].
Formylation is also a very important process because the formate esters serve as a useful synthetic reagent and
intermediate. In addition, deformylation can be effected selectively in the presence of acetate or other ester protecting
groups [1]. Furthermore if the alcoholic group is planned later in synthetic scheme, deformylation can be realized via
direct oxidation [16]. Due to the instability of the anhydride and the acid chloride of formic acid, formylation of
alcohols by formic acid and transesterification using ethyl formate are important synthetic reactions. Several catalysts,
such as Sc(OTf) [17], TMSOTf [18], PPh /CBr [19], In(OTf) [20], Bi(OTf) [21], K CoW O Á3H O [22], chloral
3
3
4
3
3
5
12 40
2
[
23], Al(HSO ) [24], sulfuric acid ([3-(3-silicapropyl)sulfanyl]-propyl) ester [25], silphos [26], silica triflate [27] and
4 3
PBBS [28] have been used for formylation of alcohols.
In continuation of our studies on catalytic application of N-halo compounds as organocatalyst in organic chemistry
[29–31], we have found that the inexpensive and commercially available p-toluenesulfonyl chloride, used widely as
sulfonyl transfer reagent [32], has found little application as chlorinating agent [33]. Very recently, for the first time we
reported catalytic application of p-toluenesulfonyl chloride ( p-TsCl) as S-halo reagent in organic transformations
*
Corresponding authors.
E-mail addresses: Khazaei_1326@hotmail.com (A. Khazaei), a_rostami372@yahoo.com (A. Rostami).
1001-8417/$ – see front matter # 2010 Ardeshir Khazaei. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.05.025

[(Scheme_1)TD$FIG]
A. Khazaei et al. / Chinese Chemical Letters 21 (2010) 1430–1434
1431
Scheme 1.
[34]. In this present research, we wish to report the catalytic application of p-toluenesulfonyl chloride as a source of
+
Cl for the efficient acetylation and formylation of a wide range of hydroxyl compounds under mild conditions
(
Scheme 1).
In order to optimize the reaction conditions, we first examined acetylation reactions of 1.0 mmol of 4-chlorobenzyl
alcohol with different amounts of p-TsCl (0.05–0.15 mmol) and Ac O (1–2 mL) at room temperature under solvent-
2
free conditions. It was observed that 0.1 mmol of p-TsCl in 1.5 mL of Ac O gave the best results and produced acetate
2
in very short reaction time and in quantitative yields. In order to extend the scope of this acetylation reaction, the
variety of hydroxyl compounds including primary, secondary, tertiary and benzylic alcohols, diols and phenols were
subjected for this catalyst (Table 1). In this reaction conditions, there were no elimination products in the mixture. This
Table 1
Acetylation of alcohols or phenols (1 mmol) using Ac
temperature.
2
O (1.5 mL) catalyzed with p-TsCl (0.1 mmol) under solvent-free conditions at room
a
Entry
Substrate
4-OMe–C
Time (min)
Product
Yield (isolated)/%
1
2
3
4
6
H
4
CH
CH OH
CH OH
OH
2
OH
9
7
4-OMe–C
6
H
4
CH
CH OAc
CH OAc
CH OAc
2
OAc
87
90
90
83
4-Cl–C
2,4-(Cl)
4-F–C
6
H
4
2
4-Cl–C
2,4-(Cl)C
4-F–C
6
H
4
2
2
C
6
H
3
2
15
8
6
H
3
2
6
H
4
CH
2
6
H
4
2
5
30
89
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
6
18
85
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
7
8
9
PhCH
PhCH CHCH
CH (CH CH(OH)CH
2
CH
2
OH
30
20
25
PhCH
PhCH CHCH
CH (CH CH(OAc)CH
3
2
CH
2
OAc
85
95
93
2
OH
2
OAc
3
2
)
4
3
3
2
)
4
10
43
95
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
1
1
1
2
33
83
96
89
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
1
1
1
1
3
4
5
6
30
180
115
25 h
86
81
75
87
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]

1432
A. Khazaei et al. / Chinese Chemical Letters 21 (2010) 1430–1434
Table 1 (Continued )
Entry Substrate
a
Time (min)
23
Product
Yield (isolated)/%
b
17
18
19
20
88
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
3
67
80
95
79
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
b
86
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
a
1
All products were characterized by comparison of their spectral data ( H NMR; IR) with those of authentic samples [3,7,8,15].
b
2
The ratio ROH/p-TsCl/Ac O is 1/0.2/3 mL.
method tolerates other functionalities on the substrate such as double bonds (Table 1). Also, the data in Table 1 clearly
show that diols and phenols were successfully converted to the corresponding acetate quantitative yields within a short
reaction time.
Subsequently, we discovered that formylation of a diverse range of alcohols can be carried out to obtain the
corresponding formate with formic acid in the presence of the same catalyst in good to excellent yields within a short
reaction time under solvent-free conditions at room temperature (Scheme 1 and Table 2).
The actual role of p-TsCl is not clear. However, on the basis of previously reported mechanism for applying of p-
+
TsCl for a-chlorination of ketones [33], one explanation is that p-TsCl might act as a source for the formation of Cl
which in turn activates the carbonyl groups of Ac O and HCOOH (Scheme 2). However, at this time the precise role of
p-TsCl is not clear and the actual role of this reagent should be further studied in detail.
2
Table 2
Formylation of alcohols using formic acid (3 mL) in the presence of catalytic amount of p-TsCl (0.15 mmol) at room temperature.
a
Entry
Substrate
Time (min)
Product
Yield (isolated)/%
1
2
3
4
5
6
7
4-Cl–C
4-F–C
4-NO
2,4-(Cl)
PhCH CH
PhCH(OH)Ph
CH CH(Ph)OH
6
H
4
CH
CH OH
CH
2
OH
10
5
4-Cl–C
4-F–C
4-NO
2,4-(Cl)C
PhCH CH
PhCH(OCHO)Ph
CH CH(Ph)OCHO
6
H
4
CH
CH OCHO
CH OCHO
CH OCHO
OCHO
2
OCHO
88
96
85
90
92
89
82
6
H
4
2
6
H
4
2
2
–C
6
H
4
2
OH
OH
54
10
8
2
–C
6
H
4
2
2
C
6
H
3
CH
2
6
H
3
2
2
2
OH
2
2
4
3
6
3
8
10
91
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
9
9
79
84
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
1
1
1
1
0
1
2
3
10
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
20
55
92
90
56
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
48 h
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]

A. Khazaei et al. / Chinese Chemical Letters 21 (2010) 1430–1434
1433
Table 2 (Continued )
a
Entry
Substrate
Time (min)
15 h
Product
Yield (isolated)/%
77
1
1
4
5
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
b
38
93
[
T
D
$
I
N
L
I
N
E
]
[TD$INLE]
a
1
All products were characterized by comparison of their spectral data ( H NMR; IR) with those of authentic samples [22,25,28].
b
The ratio ROH/p-TsCl/HCOOH is 1/0.3/6 mL.
[(Scheme_2)TD$FIG]
Scheme 2.
In conclusion we have reported catalytic application of p-TsCl as an inexpensive and commercially available
catalyst for acetylation and formylation of hydroxyl groups. The easy and clean work-up, short reaction times and
good to high yields are the main advantages of our protocol.
General procedure for acetylation of alcohols or phenols under solvent-free conditions: To a mixture of Ac O
2
(
1.5 mL), p-TsCl (0.1 mmol) and alcohols or phenols (1 mmol) were added, and then the mixture was stirred at room
temperature for the specified time (Table 1). The progress was monitored by TLC. After completion of the reaction,
0% aqueous NaOH (5 mL) was added, then the esters were extracted with CH Cl (3Â 10 mL) and the organic layer
1
2
2
was dried over anhydrous Na SO . Evaporation of the CH Cl under reduced pressure gave almost the pure products.
2
4
2
2
In some case, flash column chromatography on silica gel (hexane/EtOAc 10:1) provided pure.
General procedure for formylation of alcohols under solvent-free conditions: The alcohol (1 mmol) was added to a
mixture of HCOOH (3 mL) and p-TsCl (0.15 mmol). The mixture was stirred vigorously at room temperature for the
specified time (Table 2). After completion of the reaction (TLC), 10% aqueous NaOH (10 mL) was added, the mixture
was stirred for additional 5 min. Then the ester was extracted with CH Cl (3Â 10 mL) and the organic layer was dried
2
2
over anhydrous Na SO . Evaporation of the CH Cl under reduced pressure gave almost the pure products. In some
2
4
2
2
case, flash column chromatography on silica gel (hexane/EtOAc 10:1) provided pure.
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