Benzoyl peroxide-imidazole: A novel and efficient reagent for the mild conversion of alcohols or phenols into benzoates

Article abstract of DOI:10.1016/j.tetlet.2013.02.101

A very mild, one-pot, and expedient protocol for the conversion of alcohols and phenols into their corresponding benzoates using imidazole and benzoyl peroxide as a novel reagent is described.

Full text of DOI:10.1016/j.tetlet.2013.02.101

Tetrahedron Letters 54 (2013) 2412–2414
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Benzoyl peroxide–imidazole: a novel and efficient reagent for the mild
conversion of alcohols or phenols into benzoates
⇑
Najmeh Nowrouzi , Seyedeh Zahra Alizadeh
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A very mild, one-pot, and expedient protocol for the conversion of alcohols and phenols into their
corresponding benzoates using imidazole and benzoyl peroxide as a novel reagent is described.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 29 November 2012
Revised 9 February 2013
Accepted 28 February 2013
Available online 7 March 2013
Keywords:
Benzoyl peroxide
Imidazole
Esterification
Esterification is a frequently used reaction due to its broad
utility.1 Typically, the esterification reaction is an acid-catalyzed
process, in which the conventional acid catalysts are sulfuric acid
and hydrochloric acid, and needs either of two methods to shift
the equilibrium between the reactants and products. One is re-
moval of water (azeotropically or using dehydrating agents) gener-
ated as the reaction proceeds, and the other involves the use of a
large excess of one of the reactants. Classical methods have several
disadvantages that include equipment corrosion, formation of
unwanted side products, environmental problems, and difficulties
in catalyst recovery and loss of the catalyst. To date, a variety of
esterification conditions have been developed.2–13 However, most
procedures require either the presence of strong acids, bases, or
other catalysts. Accordingly, the further development of simple
methods for direct esterification under mild conditions is desir-
able. In 2003, Palaniappan and Ram employed benzoyl peroxide
in the presence of sulfuric acid and sodium lauryl sulfate as a sur-
factant, to convert aniline into a polyaniline salt that was then used
as the catalyst in the esterification of carboxylic acids with metha-
nol at 70 °C.14 Herein, we describe a simple and mild method for
the conversion of alcohols into benzoates that uses benzoyl perox-
ide and imidazole as a novel reagent without the need for any
acidic catalyst.
in refluxing acetonitrile gave the best result; the benzoate was ob-
tained in 88% yield after purification (Scheme 1).
Based on this outcome, the conversion of different alcohols into
benzoates was performed and the results are listed in Table 1.
This reagent system was suitable for the conversion of primary,
secondary, and benzylic alcohols into their corresponding benzo-
ates. The reaction with primary alcohols was faster in comparison
to those of more bulky secondary alcohols. For example, 2-phenyl-
ethanol (Table 1, entry 6), underwent the reaction much faster and
in higher yield than 1-phenylethanol (Table 1, entry 7).
In the case of a sterically hindered tertiary alcohol (Table 1,
entry 11), no desired product was formed even after reflux for a
prolonged time.
Having successfully converted various alcohols into benzoates,
we sought to extend this methodology to the direct preparation
of phenolic benzoates. Hence, reactions between benzoyl peroxide,
imidazole, and various phenols were carried out to afford the
desired products. As can be seen in entries 12–17 in Table 1, the
reactions proceeded quite well with phenols. Phenols with elec-
tron-donating or electron-withdrawing groups reacted smoothly
under mild conditions to afford the corresponding benzoates in
moderate to high yields.
The reaction of benzoyl peroxide and imidazole with the elec-
tron-rich phenol, 4-methoxyphenol (Table 1, entry 16) was
Initially, the reaction conditions were optimized using benzyl
alcohol as a model compound.
Reaction of benzoyl peroxide (1.5 equiv) and imidazole
(4.0 equiv), followed by the addition of 1.0 equiv of benzyl alcohol
(PhCO2)2 (1.5 equiv)
OH
imidazole (4.0 equiv)
O
CH3CN, reflux
O
1.0 eq
⇑
Corresponding author. Tel.: +98 771 4222341; fax: +98 771 4541494.
E-mail address: nowrouzi@pgu.ac.ir (N. Nowrouzi).
Scheme 1.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.02.101

N. Nowrouzi, S. Z. Alizadeh / Tetrahedron Letters 54 (2013) 2412–2414
2413
Table 1
Table 1 (continued)
Synthesis of alkyl and phenolic benzoates using benzoyl peroxide and imidazole in
refluxing acetonitrile
Entry Alcohol
Benzoate
Time
(h)
Yielda
(%)
Entry Alcohol
Benzoate
Time
(h)
Yielda
(%)
OH
NO2
O2N
O
O
OH
15
24
45
O
O
O2N
O
1
3
88
55b
75
90
14
NO2
1
OH
O
OH
O
16
2
85
92
O
O
MeO
MeO
2
2
MeO
MeO
15
2
OH
OH
O
O
17
18
2.5
Br
Cl
3
3.5
3.5
O
Br
Cl
16
3
O
OH
Cl
Cl
O
OH
OH
O
4
6
70
O
4
17
NO2
O
NO2
a
Isolated yield.
O
b
4-Methoxybenzaldehyde was obtained as a by-product.
5
24
2
55
91
70
72
60
5
OH
N
NH2
PhCO2
O
O
6
7
8
O
O
O
Ph
N
O
Ph
N
N
6
NH
+
Ph
O
O
O
OH
I
O
O
3.5
2
N
NH
ROH
NH
N
N
Ph
PhCOOR
7
N
N
NOH
O
-
-
OH
II
5
O
5
Scheme 2.
8
OH
successful and gave 4-methoxyphenyl benzoate in 85% yield after
2 h, but lower yields and longer reaction times were observed with
phenols bearing electron-withdrawing groups on the phenyl moi-
ety. Analysis of the results of the reactions with nitro phenols (Ta-
ble 1, entries 14 and 15), revealed that the nitro group had a
negative effect on the rate and yield of the reaction, as the elec-
tron-withdrawing properties of the nitro substituent(s) reduce
the nucleophilic character of phenol. In addition to the electronic
factors, steric factors also affected the reaction in terms of time
and yield. Comparison of entries 13 and 14 indicated that the pres-
ence of an ortho substituent on the phenol ring decreased the yield
and increased the reaction time.
The stereochemical outcome of the reaction was then probed
utilizing (À)-menthol as a secondary, chiral alcohol. Using benzoyl
peroxide, imidazole, and (À)-menthol, we obtained menthyl ben-
zoate in 50% yield with complete retention of configuration.15
The retention of configuration is thought to arise through a direct
attack of the alcohol on the carbonyl carbon atom of the interme-
diate II (Scheme 2).
O
5
5
9
2
O
9
O
10
24
50
O
OH
10
OH
11
—
48
2
—
OH
O
12
93
O
11
OH
O
13
14
O2N
O2N
4
82
60
O
O2N
12
Although benzoyl peroxide is a radical initiator, nevertheless,
there are many reports in the literature that use benzoyl peroxide
in a polar mechanism.16 Several observations support the proposed
pathway outlined in Scheme 2. (1) Optimization experiments
showed that polar solvents, which are unfavorable for free radical
reactions, increased the rates of these reactions. (2) Imidazole
OH
NO2
O
24
O
13

2414
N. Nowrouzi, S. Z. Alizadeh / Tetrahedron Letters 54 (2013) 2412–2414
shows a useful promoting ability in this system and increasing its
molar ratio accelerates the rate of the reaction. It appears that
imidazole enhances the reactivity of the reagent system with the
formation of intermediates I and II and also neutralizes the liber-
ated carboxylic acid. (3) The overall yields of these reactions de-
pend mostly on the electronic nature of the substituents on the
benzyl alcohols or phenols in such a manner that electron-donat-
ing groups increase the yield of the benzoate formation and the
presence of electron-withdrawing groups diminishes the yield.
(4) We observed that (À)-menthol was converted into its benzoate
with retention of the configuration of the stereogenic center. (5)
The products of these reactions do not correspond to those of the
known radical decomposition of peroxides.
In addition to the above observations, the product of the reac-
tion of cis-3-hexen-1-ol (an alcohol with a C@C bond), also con-
firmed the polar mechanism. Thus, cis-3-hexen-1-ol was added
to a mixture of imidazole and benzoyl peroxide under the opti-
mized conditions. After 6 h, (Z)-hex-3-enyl benzoate was obtained
in 70% yield (Table 1, entry 18). Formation of this product is consis-
tent with the proposed mechanism shown in Scheme 2. Therefore,
a free radical mechanism for these reactions does not seem likely.
In conclusion, a simple and mild one-pot protocol for the con-
version of alcohols and phenols into benzoates using benzoyl per-
oxide and imidazole as a novel reagent has been developed.17 The
reactions do not require a dehydrating agent nor azeotropic re-
moval of water. Furthermore, the simple procedure, availability,
safety, and ease of handling of the reagents, no requirement for
additives, and no neutralization or washing steps during the
work-up are advantages of this reagent system.
References and notes
1. (a) Otera, J. Esterification Methods. Reactions and Applications; Wiley-VCH:
Weinheim, Germany, 2003; (b) Larock, R. C. Comprehensive Organic
Transformations, 2nd ed.; VCH: New York, 1999; (c) Franklin, A. S. J. Chem.
Soc., Perkin Trans. 1 1998, 2451; (d) Franklin, A. S. J. Chem. Soc., Perkin Trans. 1
1999, 3537.
2. Iranpoor, N.; Firouzabadi, H.; Khalili, D.; Motevalli, S. J. Org. Chem. 2008, 73,
4882.
3. Soltani Rad, M. N.; Behrouz, S.; Faghihi, M. A.; Khalafi-Nezhad, A. Tetrahedron
Lett. 2008, 49, 1115.
4. Saito, Y.; Yamaki, T.; Kohashi, F.; Watanabe, T.; Ouchi, H.; Takahata, H.
Tetrahedron Lett. 2005, 46, 1277.
5. Manabe, K.; Sun, X.; Kobayashi, S. J. Am. Chem. Soc. 2001, 123, 10101.
6. Sejidov, F. T.; Mansoori, Y.; Goodarzi, N. J. Mol. Catal. A: Chem. 2005, 240, 186.
7. Sharma, P.; Vyas, S.; Patel, A. J. Mol. Catal. A: Chem. 2004, 214, 281.
8. Wakasugi, K.; Nakamura, A.; Iida, A.; Nishii, Y.; Nakatani, N.; Fukushima, S.;
Tanabe, Y. Tetrahedron 2003, 59, 5337.
9. Won, J.; Kim, H.; Kim, J.; Yim, H.; Kim, M.; Kang, S.; Chung, H.; Lee, S.; Yoon, Y.
Tetrahedron 2007, 63, 12720.
10. Salome, C.; Kohn, H. Tetrahedron 2009, 65, 456.
11. Nowrouzi, N.; Mehranpour, A. M.; Ameri Rad, J. Tetrahedron 2010, 66, 9596.
12. Mukaiyama, T.; Shintou, T.; Kikuchi, W. Chem. Lett. 2002, 1126.
13. Sarpong, R.; Heller, S. T. Tetrahedron 2011, 67, 8851.
14. Ram, M. S.; Palaniappan, S. J. Mol. Catal. A: Chem. 2003, 201, 289.
15. (a) McNulty, J.; Capretta, A.; Laritchev, V.; Dyck, J.; Robertson, A. J. J. Org. Chem.
2003, 68, 1597; (b) Silverman, R. B.; Forrester, M. T.; Gomez-Vidal, J. A. Org. Lett.
2001, 3, 2477.
16. (a) Challenger, F.; Wilson, V. J. Chem. Soc. 1927, 209; (b) Greenbaum, M. A.;
Denny, D. B.; Hoffmann, K. J. Am. Chem. Soc. 1956, 78, 2563; (c) Pautard, A. M.;
Evans, S. A., Jr. J. Org. Chem. 1988, 53, 2300; (d) Grierson, L.; Perkins, M. J.
Tetrahedron Lett. 1993, 34, 7463.
17. Typical procedure for the synthesis of benzyl benzoate (1): Benzyl alcohol (0.1 mL,
1 mmol) was added to a stirred solution of imidazole (0.272 g, 4.0 mmol) and
benzoyl peroxide (0.363 g, 1.5 mmol) in 5 mL of CH3CN at reflux. The reaction
was monitored by TLC. After completion of the reaction (3 h), the solvent was
evaporated and the residue was subjected to purification on a short column of
silica gel, using n-hexane/EtOAc (4:1) as the eluent to give benzyl benzoate
(0.186 g, 88%) as a colourless oil; dH (250 MHz, CDCl3) 7.98 (dd, 2H, J 8.4, 1.5 Hz,
Ph), 7.44-7.24 (m, 8H, Ph), 5.26 (s, 2H, CH2); dC (62.9 MHz, CDCl3) 166.4, 136.1,
133.1, 130.2, 129.7, 128.6, 128.4, 128.3, 128.2, 66.7.
Acknowledgement
We thank the Persian Gulf University Research Council for
generous partial financial support of this study (Code: PGU/FS/7-
1/1391/842).