Pentafluorophenylammonium triflate (PFPAT): An efficient, metal-free and reusable catalyst for the von Pechmann reaction

Article abstract of DOI:10.1016/j.jfluchem.2011.04.016

Pentafluorophenylammonium triflate (PFPAT) is used as an efficient catalyst in the von Pechmann condensation of phenols with β-ketoesters leading to the formation of coumarin derivatives. Short reaction times, easy and quick isolation of the products, excellent chemoselectivity, excellent yields and ease of catalyst recovery with consistent activity makes this protocol efficient and environmentally benign.

Full text of DOI:10.1016/j.jfluchem.2011.04.016

Journal of Fluorine Chemistry 132 (2011) 450–452
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Pentafluorophenylammonium triflate (PFPAT): An efficient, metal-free and
reusable catalyst for the von Pechmann reaction
a
a
Naser Montazeri a, , Samad Khaksar
, Akbar Nazari , Seyedeh Soghra Alavi ,
*
b,**
Seyed Mohammad Vahdat b, Mahmood Tajbakhsh c
a Chemistry Department, Faculty of Sciences, Islamic Azad University, Tonekabon, Iran
b Chemistry Department, Islamic Azad University, Ayatollah Amoli Branch, Amol, Iran
c Chemistry Department, Mazandaran University, Babolsar, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Pentafluorophenylammonium triflate (PFPAT) is used as an efficient catalyst in the von Pechmann
Received 19 January 2011
Received in revised form 25 April 2011
Accepted 26 April 2011
Available online 4 May 2011
condensation of phenols with
b-ketoesters leading to the formation of coumarin derivatives. Short
reaction times, easy and quick isolation of the products, excellent chemoselectivity, excellent yields and
ease of catalyst recovery with consistent activity makes this protocol efficient and environmentally
benign.
ß 2011 Elsevier B.V. All rights reserved.
Keywords:
Pentafluorophenylammonium triflate
Coumarins
Pechmann reaction
Phenols
In memory of Dr. Farhad Ramazanian.
1. Introduction
to produce coumarins. Classically, the process consists of the
condensation of phenols with
b-ketoesters in the presence of a
The ubiquitous coumarins have attracted more and more
attention in both industrial and academic fields for decades. This
interest arises from the fact that a variety of natural and synthetic
compounds which contain the coumarin substructure exhibit
significant biological activities such as inhibitory of platelet
aggregation [1], antibacterial [2], anticancer [3], inhibitory of
variety of reagents to give good yields of 4-substituted coumarins
[10]. Several acid catalysts have been used in the von Pechmann
reaction including sulfuric acid [11], aluminium chloride [12],
phosphorus pentoxide [13], trifluoroacetic acid [14] and other
acids [15]. However, in many of these methods an excess amount
of acid is needed to complete the reaction; for instance, reactions
conducted in sulfuric acid [11] and trifluoroacetic acid [14]
required 10–12 and 3–4 equivalent amount of acid respectively.
Disposal of the acidic waste in these procedures also causes
environmental pollution. Several other acid catalysts, including
Lewis acids, are known to affect this condensation [16]. However,
moisture sensitivity of the majority of Lewis acids to the water
produced in the Pechmann reaction renders them unsuitable for
use in large scale applications. Ionic liquids [17] and microwave
irradiation [18] have been applied to the Pechmann reaction, but
these methods also generated strongly acidic wastes and they
utilize highly expensive and non-recyclable reagents. To improve
the above mentioned problems, a number of heterogeneous
alternatives such as Amberlyst ion-exchange resins [19], zeolites
[20,21], montmorillonite K-10 [22], polyaniline sulfate salt [23,24],
heteropoly acids [25], nafion resin/silica nanocomposites [26],
nano-crystalline sulfated-zirconia [27] and sulfonic acid function-
alized SBA-15 silica [28] have been employed for this purpose in
steroid 5
a
-reductase [4] and inhibitory of HIV-1 protease [5]. For
-methylumbelliferone)
instance, 7-hydroxy 4-methyl coumarin (
b
is used as fluorescent brightener, efficient laser dye, standard for
fluorometric determination of enzymatic activity and as a starting
material for the preparation of insecticide and furano coumarins
[6–8]. Moreover, coumarins act also as intermediates on the
synthesis of fluorocoumarins, chromenes, coumarones, and 2-
acylresorcinols [9]. Owing to their important applications, various
synthetic methodologies for coumarin derivatives have been
developed. The von Pechmann reaction is a venerable reaction
and it is one of the most simple and straightforward methods used
* Corresponding author.
** Corresponding author. Fax: +98 121 2517024.
E-mail addresses: montazer50@toniau.ac.ir (N. Montazeri),
S.khaksar@iauamol.ac.ir, samadkhaksar@yahoo.com (S. Khaksar).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.04.016

N. Montazeri et al. / Journal of Fluorine Chemistry 132 (2011) 450–452
451
O
O
(phenol to catalyst weight ratio = 1); nafion resin/silica nanocom-
posites [26] and Amberlyst ion-exchange resins [19] are required
in phenol to catalyst weight ratio of 2, for giving 80–96% yield of 7-
hydroxy-derivative. Therefore, the search continues for a better
catalyst for the synthesis of coumarins in terms of operational
simplicity, reusability, economic viability, and greater selectivity.
Organocatalysis has greatly gained importance in organic synthe-
sis as it provides a high selectivity with fewer by-products, thus
making it an environmentally benign alternative to chemical
transformations [29]. Recently, Tanabe et al. reported the
O
O
OH
PFPAT, 10 mol %
R'
R'
+
OR
Toluene, 110 ºC, 3 h
Scheme 1.
the Pechmann condensation. Although these methods are effec-
tive, but some of them suffer from either a tedious synthetic
methodology [23,24], or requirement of a large amount of catalyst
to complete the reaction. For example, zeolites [20,21] and
Amberlyst [19] are required in almost stochiometric amount
application
of
pentafluorophenylammonium
triflate
(C6F5N+H3ÁOTfÀ; PFPAT) as a novel organocatalyst in organic
transformation such as esterification of carboxylic acids with
alcohols [30], C-acylations of enol silyl ethers or ketene silyl
(thio)acetals with acid chlorides[31] and Mukaiyama aldol and
Mannich reactions using ketene silyl acetals with ketones and
oxime ethers [32]. However, there are no any reports about the
application in catalysis as a Brønsted acidic organocatalyst in the
von Pechmann condensation. Herein, we report the first example
of the PFPAT-catalyzed one-pot synthesis of coumarins in toluene
at 110 8C (Scheme 1).
Table 1
Pechman reaction of different substituted phenols with ethyl-acetoacetate
employing PFPAT.
Entry
1
Phenol
Product
Yield [Ref.]
90 [28]
OH
HO
HO
O
O
2
3
95 [33]
95 [28]
OH
OH
OH
OH
OH
HO
HO
O
O
O
O
HO
HO
2. Results and discussion
To initiate our study, the reaction of ethyl acetoacetate with
resorcinol was chosen as a model reaction in the presence of PFPAT
(10 mol%) in toluene at room temperature, but no reaction was
occurred. Much to our surprise, when we carried out the reaction in
toluene at 110 8C, the corresponding coumarin derivative (Table 1,
entry1) was obtained in high yield (90%) after 3 h. A wide range of
structurally varied phenols reacted smoothly and quickly to give
the corresponding coumarins in high yield and purity as listed in
Table 1.
The remarkable feature of this improved protocol is the wide
stability of a variety of functional groups, such as ether, hydroxy,
nitro, alkyl and amino group under the present reaction conditions.
It is worth mentioning that substrates like phenol, nitrophenols
and cresols which failed to react in many of the protocols reported
in the literature [17a,33], showed better reactivity giving moderate
to excellent yields. Substrates (entries 1–8) having electron-
donating groups in the para position to the site of electrophilic
substitution gave higher yields of the corresponding coumarins.
Phenols, without having electron-donating groups (entry 10) or
with an electron withdrawing group (entry 11) gave lower yield of
OH
4
5
6
90 [28]
90 [28]
90 [33]
O
OH
OH
O
O
O
O
O
HO
HO
HO
OH
HO
O
O
7
8
9
85 [28]
90 [28]
80 [28]
OH
O
O
O
the products. In the case of m-aminophenol (entry 12)
a
OH
O
O
chemoselective reaction was occurred and 7-amino-4-methyl
coumarin was formed in good yield.
The PFPAT catalyst was easily separated from the reaction
mixture after work-up and recrystallized from hot hexane to give a
pure PFPAT for subsequent use. For example, the reaction of ethyl
acetoacetate with resorcinol afforded the corresponding coumarin
in 90, 90 and 88% isolated yield over three cycles.
OH
O
O
10
11
12
60 [33]
60 [33]
70 [28]
OH
O
3. Conclusions
In conclusion, we have successfully demonstrated the catalytic
activity of PFPAT in the von Pechmann condensation of phenols
OH
OH
O
O
with
b-ketoesters leading to the formation of coumarin deriva-
tives. In addition to its simplicity and mild reaction conditions,
this method has the ability to tolerate a wide variety of
substitutions in both components, which can afford different
substituted coumarins in high yields. The present practical
method is a new candidate for synthetic chemists to apply for
the von Pechmann reaction.
O2N
H2N
O2N
H2N
O
O

452
N. Montazeri et al. / Journal of Fluorine Chemistry 132 (2011) 450–452
4. Experimental
Acknowledgments
4.1. Typical experimental procedure
This research is supported by the Islamic Azad University,
Tonekabon and Ayatollah Amoli Branch.
A mixture of resorcinol (1 mmol), ethyl acetoacetate or
methyl acetoacetate (1.1 mmol) dissolved in 3 ml toluene, and
PFPAT (10 mol%) was refluxed with stirring for 3 h. The reaction
mixture, after being cooled to room temperature was poured
onto crushed ice and stirred for 5–10 min. The crystalline
product was collected by filtration under suction (water
aspirator), washed with ice-cold water (40 ml) and then
recrystallized from hot ethanol to afford pure 7-hydroxy-4-
methylcoumarin as colorless prisms (90%), mp 185–187 8C. The
filtrate was concentrated under reduced pressure and then
recrystallized from hot hexane to recover the PFPAT for
subsequent use. This procedure was followed for the prepara-
tion of all the 4-substituted coumarins listed in Table 1. All the
compounds were identified by comparison of analytical data (IR,
1H NMR, and 13C NMR) and mp with those reported [28].
Spectroscopic data for selected examples follow:
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