A TFAA-H3PO4-mediated direct, metal-free and high-speed synthesis of aryl carboxylate esters from phenols

Article abstract of DOI:10.1016/j.jfluchem.2009.02.006

An operationally simple, mild and single-step method for the direct and metal-free synthesis of aryl carboxylate esters is described under a solvent free condition. The reaction of phenols including 2-naphthol (or 1-naphthol) with a variety of carboxylic acids in the presence of TFAA and 85% H₃PO₄ provided a range of aryl carboxylate esters in good yields within few minutes.

Full text of DOI:10.1016/j.jfluchem.2009.02.006

Journal of Fluorine Chemistry 130 (2009) 505–508
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Journal of Fluorine Chemistry
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Short communication
A TFAA–H3PO4-mediated direct, metal-free and high-speed synthesis of aryl
carboxylate esters from phenols
Kavitha Kankanala a,b, Vangala Ranga Reddy c, Khagga Mukkanti a, Sarbani Pal b,
*
a J N T University, Kukatpally, Hyderabad 500072, India
b Department of Chemistry, MNR Degree and PG College, Kukatpally, Hyderabad 500072, India
c Dr. Reddys Laboratories Limited, Integrated Product Development, Bachupally, Hyderabad 500055, India
A R T I C L E I N F O
A B S T R A C T
Article history:
An operationally simple, mild and single-step method for the direct and metal-free synthesis of aryl
carboxylate esters is described under a solvent free condition. The reaction of phenols including 2-
naphthol (or 1-naphthol) with a variety of carboxylic acids in the presence of TFAA and 85% H3PO4
provided a range of aryl carboxylate esters in good yields within few minutes.
ß 2009 Elsevier B.V. All rights reserved.
Received 16 January 2009
Received in revised form 9 February 2009
Accepted 10 February 2009
Available online 21 February 2009
Keywords:
Trifluoroacetic anhydride
Phosphoric acid
O-acylation
Phenol
Naphthol
Carboxylic acid
1. Introduction
montmorillonite-Ti4+ [20], metal triflates in [bmim]PF6 [21],
Mn(OAc)3 [22], TiO(acac)2 [23], diarylammonium arensulfonate
We describe the TFAA–H3PO4-mediated direct O-acylation of
phenol and 2-naphthol (or 1-naphthol) using a free carboxylic acid,
such reaction is often carried out using acid chloride or anhydride.
Aryl carboxylate esters (e.g. ArOCOR, 1) are of commercial
interest because of their usage as components of liquid crystals and
polyarylated liquid crystal polymers [1]. Besides, these esters are of
medicinal interest as many of these derivatives have been studied
as potential prodrug of phenolic drugs [2,3]. Moreover, Aspirin or
acetylsalicylic acid, a well-known anti-inflammatory drug belongs
to this class (Fig. 1) [4]. The most convenient and straightforward
method for the preparation of 1 is esterification of phenols.
However, unlike alcohols, –OH group of phenol is less reactive
towards esterification and therefore requires activation of the
corresponding carboxylic acid used. This can be achieved either via
conversion of carboxylic acid to more reactive functional groups,
such as anhydride [5–7] and acyl halide [8–10], or via in situ
activation in the presence of coupling reagents. These include
trifluoroacetic anhydride (TFAA) [11], 2-chloro-1-methylpyridi-
nium iodide [12], BOP [13], DCC [14], PPE [15], N,N-bis(2-oxo-3-
oxazolidinyl)phosphordiamidic chloride [16], CCl4/PPh3 [17],
diphenyl(1,2-benzisoxazol-3-yl)phosphate [18], Me2NSO2Cl [19],
[24], and several other condensing agents [25–30]. Some of these
methods however, are associated with several drawbacks such as
moderate yields, long reaction times, use of expensive reagents,
and the use of volatile and environmentally harmful organic
solvents. Moreover, the use of common acylating agent, i.e.
moisture sensitive acid chlorides often cause environmental
pollution and their preparation typically involve the use of thionyl
chloride and oxalyl chloride. Thus, there is a need to develop
alternative and practical method for the preparation of 1.
Previously, we have reported the use of TFAA/H3PO4 as an efficient
catalyst system for C-acylation of benzothiophenes [31] and
naproxen [32]. Herein we report a mild, single-step and metal-free
process for the synthesis of 1 via TFAA/H3PO4-mediated direct O-
acylation of phenol and 2-naphthol (or 1-naphthol).
2. Results and discussion
In the beginning of our study we examined the reaction of
phenol (2) with benzoic acid (3a, Ar = C6H5) in the presence of TFAA
(4.0 mol) and 85% H3PO4 (1.0 mol) at room temperature (Scheme
1). The reaction was completed within 5.0 min and the results are
summarized in Table 1. Based on earlier reports [33–35] and our
previous observation we expected the formation of C-acylated
product (path b, Scheme 1) as a major or side product. However, we
observed that only O-acylated product (path a, Scheme 1) was
* Corresponding author. Tel.: +91 40 23041488.
E-mail address: sarbani277@yahoo.com (S. Pal).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.02.006

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K. Kankanala et al. / Journal of Fluorine Chemistry 130 (2009) 505–508
Scheme 1. TFAA/H3PO4-mediated reaction of phenol (2) and carboxylic acids (3).
formed exclusively with 92% yield (entry 1, Table 1). While the
initial reaction was carried out using 1.0 mol of H3PO4, we then
reduced its amount to 0.1 mol in order to assess its role in the
present O-acylation process. A slow progress of reaction was
observed but it did not reach to the completion even after 2 h and
the product yield was decreased to 67% (entry 2, Table 1). The
reaction was also carried out in the absence of H3PO4 when the
product yield was further decreased to 20% (entry 3, Table 1). These
observations clearly indicated that the presence of H3PO4 is
essential to complete the O-acylation process successfully.
Having established the optimum condition we then examined
the reactivity of phenol (2) towards other carboxylic acids.
Accordingly, a number of carboxylic acids were reacted [36] with
2 and yields of the corresponding products are shown in Table 1. As
evident from Table 1 that the carboxylic acid may contain an olefin
(3b) or a mild electron donating group such as chloro (3c) and
methyl (3e) or a strong electron donating group, e.g. methoxy (3d)
(entries 4–7, Table 1). We have observed that the success of the
TFAA/H3PO4-mediated O-acylation reaction of phenol was par-
tially dependent on the nature of group present on the benzene
ring of the carboxylic acid employed. This was supported by the
fact that p-nitro benzoic acid did not provide the desired product at
room temperature. However, the desired product was isolated in
78% yield when the reaction was carried out at an elevated
temperature (50 8C) for 15 min (entry 8, Table 1).
Fig. 1. Examples of aryl carboxylate ester drug: Aspirin and its NO-donating
derivatives.
Table 1
TFAA/H3PO4-mediated O-acylation of phenol (2) with carboxylic acids (3)a.
Entry
Carboxylic acids (3)
Products (1a–e)
Conditions
Yield%b
1.
2.
3.
4.
PhCO2H 3a
PhCO2Ph 1a
RT; 5.0 min
RT; 2 h
92
67c
20d
87
3a
3a
1a
1a
RT; 2 h
RT; 14 min
3b
1b
5.
RT; 5.0 mn
89
To extend the scope and generality of this methodology we then
examined the reaction of substituted phenols (4) with acetic acid
(Scheme 2) and 2-naphthol (6) with carboxylic acids (Scheme 3).
The reactions of
4 with acetic acid required an elevated
temperature, i.e. 50 8C to obtain the optimum yields of products
(entries 1–3, Table 2) perhaps due to the less reactivity of acetic
acid towards the present O-acylation process in compared to
aromatic acids 3a–e. However, the reaction of 4a with benzoic acid
proceeded well at room temperature affording the desired product
in 78% yield (entry 4, Table 2). Similarly, the reaction of 2-naphthol
(6) and 1-naphthol with acetic acid required an elevated
temperature (entries 3 and 4, Table 3) to give the desired product
7c and 7d in 96 and 87% yield, respectively. Overall, the O-acylated
products (5a–d and 7a–d) were isolated in good yields indicating
3c
1c
6.
RT; 5.0 min
84
3d
3e
1d
7.
8.
RT; 5.0 min
86
78
1e
50 8C; 15 min
Scheme 2. Synthesis of esters (5) from substituted phenols (4) and acetic acid.
3f
1f
a
All the reactions were carried out using 2 (1.0 mol), 3 (1.0 mol) in the presence
of TFAA (4.0 mol) and 85% H3PO4 (1.0 mol) at room temperature.
b
Yield of isolated product.
c
The reaction was carried out using 0.1 mol of H3PO4.
d
Scheme 3. Synthesis of esters (7) from 2-naphthol (6) and carboxylic acids (3).
The reaction was carried out in the absence of H3PO4.

K. Kankanala et al. / Journal of Fluorine Chemistry 130 (2009) 505–508
507
Table 2
TFAA/H3PO4-mediated O-acylation of substituted phenols (4) with acetic acid/benzoic acida.
Entry
1.
Phenols (4)
Products (5)
Conditions
Yield%b
77
50 8C; 5 min
4a
5a
2.
3.
50 8C; 10 min
75
4b
5b
5c
50 8C; 5 min
72
78
4c
4a
4.
RT; 5 min
5dc
a
All the reactions were carried out using 4 (1.0 mol), acetic acid (1.0 mol) in the presence of TFAA (4.0 mol) and 85% H3PO4 (1.0 mol) at room temperature.
b
c
Yield of isolated product.
Benzoic acid (3a) was used in place of acetic acid.
Table 3
reagents or catalysts, inert or anhydrous atmosphere and works
well either at room temperature or at 50 8C providing the O-
acylated products in good to excellent yields within few minutes.
Because of operational simplicity, clean and mild reaction
conditions and significantly shorter reaction time the present
metal-free process would find wide usage.
TFAA/H3PO4-mediated O-acylation of 2-naphthol (6)/1-naphthol with carboxylic
acids (3)a.
Entry Carboxylic
Products (5)
Conditions
Yield%b
acids (3)
1.
3a
50 8C; 15 min
86
Acknowledgment
7a
7b
Authors (K. Kavitha and S. Pal) thank Mr. M.N. Raju, the
chairman of MNR Educational Trust for constant support and
encouragement.
2.
3.
3c
50 8C; 15 min
91
96
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