Transition metal-free oxidative esterification of benzylic alcohols in aqueous medium

Article abstract of DOI:10.1039/c4ob01524j

Oxidative esterification of benzylic alcohols with a catalytic amount of HBr-H₂O₂ in aqueous medium under mild conditions is reported with a wide range of substrate scope for both benzylic and aliphatic alcohols. The conditions are also suitable for selective mono-esterification of ethylene glycol and glycerol. With catalytic amounts of HBr (20 mol%) and H₂O₂, the generation of reactive intermediate species BrOH has been ascertained by UV-visible spectra.

Full text of DOI:10.1039/c4ob01524j

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: A. Subbarayappa,
S. Samanta, V. Pappula and M. Dinda, Org. Biomol. Chem., 2014, DOI: 10.1039/C4OB01524J.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/obc

Organic & Biomolecular Chemistry
Page 1 of 4Organic &
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C4OB01524J
Biomolecular Chemistry
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTICLE TYPE
Transition metal-free oxidative esterification of benzylic alcohols in
aqueous medium
Supravat Samanta,a Venkatanarayana Pappula,a Milan Dindaa and Subbarayappa Adimurthy* a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Oxidative esterification of benzylic alcohols with catalytic amount of HBrꢀH2O2 in aqueous medium under mild conditions is reported
with wide range of substrate scope for both benzylic and aliphatic alcohols. The conditions are also suitable for selective monoꢀ
esterification of ethylene glycol and glycerol. With catalytic amount of HBr (20 mol%) and H2O2, the generation of reactive intermediate
species BrOH has been ascertained by UVꢀvisible spectra.
10
Introduction
herein, we wish to report a general catalytic oxidative crossꢀ
esterifications of benzylic and aliphatic alcohols (Scheme 1),
50 which proceeds with high selectivity under mild conditions.
Esters are the most common and fundamental building blocks
used in variety of organic transformations.1 Particularly, aromatic
carboxylic esters received much attention due to their diverse
15 interest in synthesis of organic intermediates such as polymers,
cosmetics, pharmaceuticals, agrochemicals, food additives and
advanced materials.2 As a result, remarkable progress has been
achieved by various groups over the past few years on the
synthesis of ester derivatives. Traditionally, the reaction between
20 carboxylic acids and alcohols under the assistance of activating
reagents or water abstracting reagents are well established
procedure for ester synthesis. In literature, stoichiometric
amounts of heavyꢀmetal oxidants (KMnO4, CrO3, ozone, oxone,
Nꢀiodosuccinimide) and transitionꢀmetal catalysts including
25 precious metals such as silver, palladium, ruthenium, rhodium,
gold, etc. were usually employed for the success of these
transformations.3 Metalꢀfree oxidative esterification of alcohols
are rarely reported in literature,4 also separation of metal catalyst
from products is of particular importance. Moreover, transition
30 metalꢀcatalyzed reactions also generate hazardous waste which is
environmentally problematic and hence, should to be avoided
wherever possible. Furthermore, it is also highly desirable to
develop environmentally benign oxidative esterification
processes without requirement of any metal catalyst. In
35 continuation of our efforts on the development of green and
sustainable methods for the oxidation of organic substrates,5
Scheme 1.
To the best of our knowledge, no similar HBrꢀcatalyzed reactions
are known to date. Therefore, the development of an efficient,
55 and environmentally benign catalytic system for oxidative
esterification with benzylic alcohols remains challenging.
Results and discussion
We initiated our studies with benzyl alcohol 1a as substrate and
subjected oxidative esterification with catalytic amount (20 mol
60 %) of commercially available aqueous hydrobromicacid (HBr)
and hydrogen peroxide (6.0 eqv. w.r.t 1a) in methanol at room
temperature. After 16 h the desired product methyl benzoate 3a
was obtained in 31% isolated yield (Table 1, entry 1). When the
reaction temperature was increased to 40 °C, the yield of the
65 product was also increased to 47% (Table 1, entry 2). However,
at 60 °C the product was obtained in 87% isolated yield (Table 1,
entry 3). When the reaction was performed with reducing the
amount of HBr to 10 and 15 mol%, the yield was decreased to
76% and 81% respectively (Table 1, entries 4 and 5). Further no
70 improvements were observed either by decreasing the oxidant or
in absence of both oxidant and HBr catalyst (Table 1, entries 6 ꢀ
10). By decreasing the reaction time from 16 h, the yield of the
product was dropped (Table 1, entries 11ꢀ13). Then we focused
on the effect of other solvents on the oxidative esterification of 1a
a
Academy of Scientific & Innovative Research
CSIR-Central Salt and Marine Chemicals Research Institute, G. B. Marg,
40 Bhavnagar –364 002, India
E-mail: adimurthy@csmcri.org
†Electronic Supplementary Information (ESI) available: [General
procedure; copies of NMR spectra and mass data for selective
compounds.] See DOI: 10.1039/b000000x/
45
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Organic & Biomolecular Chemistry
Page 2 of 4
View Article Online
DOI: 10.1039/C4OB01524J
Table 1. Optimization of reaction conditions for 3aa
30 Table 2. Substrate scope of esterificationa
R2
HBr (0.2 mmol)
H2O2 (6.0 mmol ), 60°C
OH
R2OH
R1
R1
2
1
3
OMe
3a;87%
OMe
OMe
OMe
OMe
Cl
Br
O2N
3b; 85%
3d;71%
3c; 92
3e; 83%
OMe
OMe
OMe
OMe
OEt
NO2
F
Cl
Br
3f;73%
3i; 82%
3g; 72%
3h;79%
3j; 84%
OnBu
OnBu
OEt
OEt
OEt
Br
Cl
3n; 80%b
3o; 68%b
3k; 89%
3l; 69%
3m; 81%
OnBu
OnBu
OnOct
OnOct
OnOct
Cl
Br
Cl
3p; 79%b
3q; 85%b
3r; 76%b
3s; 65%b
3t;77%b
OnOct
O
OMe
OMe
OMe
Br
N
S
3u; 80%b
3w; 0%a,b
3x; 0%a,b
3v; 65%
aReaction conditions:1.0 mmol of benzyl alcohol 1, 6.0 mmol of H2O2,
0.2 mmol HBr (46% aqueous solution), in 2.0 mL of 2 at 60 °C for 16 h;
isolated yield. bReactions carried out at 70 ꢀ75 °C.
35 strategy for thiophenꢀ2ꢀylmethanol with methanol, the
corresponding methyl ester 3v was also obtained in 65% yield.
Unfortunately, the present catalytic system is not applicable for
pyridinꢀ2ꢀylmethanol and unsaturated aromatics.
aReaction conditions:1.0 mmol of benzyl alcohol 1a, 6.0 mmol of H2O2,
0.2 mmol HBr (46% aqueous solution), in 2.0 mL of MeOH at 60 °C for
b
c
d
5
16 h. Isolated yield. 0.1 mmol of HBr was used. 0.15 mmol HBr was
used. eAbsence of HBr. f5.0 mmol of MeOH was added. (DCE: Dichloro
ethane)
Finally, to explore the potential applications of this protocol, we
40 investigated the selective mono esterification of polyalcohols
with benzylic alcohols under the optimized conditions (Table 3).
To our delight, we obtained good yields of mono esters of
ethylene glycol and naturally abundant glycerol with
representative benzylic alcohols 5aꢀ5f.
with methanol by fixing temperature (60 °C), time (16 h), catalyst
(20 mol%) and oxidant (6.0 equivalents). The reaction was not
10 favorable in various solvents (CH3CN, DMF, DMSO, CHCl3,
CH2Cl2, DCE, CH2Br2, toluene, water, and 1,4ꢀdioxane) screened
out for the present transformation (Table 1, entries 14ꢀ23).
45 Table 3. Monoesterification of polyalcoholsa
Having identified the optimized reaction conditions, we turned
our attention to the examination of substrate scope and limitation
15 of this catalytic oxidation system (Table 2). As evident from
Table 2, the oxidative esterification of a variety of benzyl
alcohols with methanol were smoothly transformed into the
corresponding products in moderate to excellent yield. The
presence of a variety of electronꢀdonating/ꢀwithdrawing groups
20 (CH3, Cl, Br, F, and NO2) at either (para/meta) position of benzyl
alcohol could be tolerated and afford the corresponding methyl
ester in 71ꢀ92% yields (3a–3i). With ethanol similar yields of
corresponding ethyl ester were obtained (3j–3m). The variety of
benzyl alcohols with aliphatic alcohols such as nꢀbutanol and nꢀ
25 octanol were also afforded the corresponding butyl and octyl
esters (3n–3u). However, for long chain aliphatic alcohols it
required 70ꢀ75 °C for efficient conversion. Electronic effects
associated with electronꢀ donating/withdrawing substituents did
not affect the efficiency of the process. Then we extended the
a Reaction conditions:1.0 mmol of benzyl alcohol 1, 6.0 mmol of H2O2,
0.2 mmol HBr (46% aqueous solution), in 2.0 mL of 4 at 70 ꢀ75 °C for 16
h; Isolated yield.
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 4
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C4OB01524J
To understand the reactive species involved in the present
transformation, we recorded the UVꢀabsorption spectra of
mixture of HBrꢀH2O2 system, in presence and absence of organic
substrate (Fig 1). The absorption spectra were recorded at
different interval (1, 3, 5 and 7 h) of time. As evident from the
45 Conclusion
In conclusion, we have developed transition metalꢀfree oxidative
esterification of benzylic alcohols with catalytic HBr in aqueous
medium. The method has no influence on both electronꢀ
donating/withdrawing substituents and also applicable for
50 selective monoꢀesterification of ethylene glycol and glycerol
under mild conditions. We have also demonstrated the inꢀsitu
generation of the reactive species BrOH with catalytic HBrꢀH2O2
using UVꢀvisible spectroscopic evidence and these species are
accountable for the oxidative esterification.
5
Fig 1. UVꢀAbsorption spectra of reaction mixture (a) in presence of
benzyl alcohol, (b) in absence of benzyl alcohol.
plot of the absorbance v/s wavelength, the aqueous bromine
10 generated inꢀsitu from HBrꢀ H2O2 will disproportionate to BrOH
and HBr (Scheme 3). The absorption bands at 220 nm, 266 nm
and 390 nm correspond to HBr, BrOH and Br2 respectively.6
Figure 1, indicates the different species formed during the
reaction (fig 1a) in presence of alcohol, the peak at 220 nm (HBr)
15 decreases initially and then slowly increases with the progress of
the reaction.7 Initially, the peak at 266 nm (BrOH) reaches
maximum and then it completely disappears as reaction proceeds.
This clearly indicates that reactive species BrOH will oxidize the
alcohol to aldehyde and bromide atom ends up as HBr after
20 completion of the reaction. Whereas in Fig 1b, in absence of
benzyl alcohol, the peak at 266 nm (BrOH) increases as there was
no organic substrate available for oxidation by these species in
the system. In this manner the catalytic HBr generates the
reactive species inꢀsitu to accelerate the oxidative esterification of
25 alcohols to methyl esters and makes the process environmentally
friendly reagent dispensing the use of precious/heavy metals.
Further, to confirm the radical reaction pathway,4 we performed a
55
Scheme 3. Proposed reaction mechanism
Acknowledgment.
(CSIRꢀCSMCRIꢀ Communication No. 109/2014). S. S, M. D. and
P.V. are thankful to CSIR and UGC New Delhi, India for their
60 fellowships. We are thankful “Analytical Discipline and
Centralized Instrumental Facility” division of CSMCRI for
providing instrumentation facilities. We also thank, CSIR (CSꢀ
0123 INDUS MAGIC) and DST, Govt. India (SR/S1/OCꢀ
13/2011) for financial support.
65 Notes and references
1. (a) J. Otera, Esterification: Methods, Reactions and Applications;
WileyꢀVCH: Weinheim, 2003; (b) R. C. Larock, Comprehensive
Organic Transformation; VCH: NewYork, 1999; (c) J. Otera, Chem.
Rev., 1993, 93, 1449–1470; (d) J. Otera, Angew. Chem., Int. Ed. 2001,
40, 2044–2045.
2. R. C. Larock, Comprehensive Organic Transformations: A Guide to
Functional Group Preparation; VCH: New York, 1989.
3. (a) A. Abiko, J. C. Roberts, T. Takemasa and S. Masamune,
Tetrahedron Lett., 1986, 27, 4537–4540; (b) B. O’Connor and G.
Just, Tetrahedron Lett., 1987, 28, 3235–3236; (c) P. J. Garegg, L.
Olsson and S. Oscarson, J. Org. Chem., 1995, 60, 2200–2204; (d) P.
Sundararaman, E. C. Walker and C. Djerassi, Tetrahedron Lett.,
1978, 19, 1627–1628; (e) B. R. Travis, M. Sivakumar, G. O. Hollist
and B. Borhan, Org. Lett., 2003, 5, 1031–1034; (f) R. Gopinah, B.
Barkakaty, B. Talukdar and B. K. Patel, J. Org. Chem., 2003, 68,
2944–2947; (g) J. H. Espenson, Z. Zhu and T. H. Zauche, J. Org.
30
Scheme 2. Mechanistic study
70
75
80
reaction under our optimized conditions using TEMPO as radical
scavenger, no desired product 3a was observed (Scheme 2). This
study supports that, the reaction proceeds through radical
mechanism. Hence, based on the above observations, a plausible
35 reaction mechanism has been proposed in Scheme 3. Firstly, the
generated bromide radical reacted with benzyl alcohol to give the
corresponding radical species I. Then the reaction of radical
species I with bromine generated benzaldehyde and bromide
radical; subsequently followed by proton abstraction to provide
40 the benzoyl radical II. The formed benzoyl radical II was further
reacted with bromide radical to give the desired benzoyl bromide.
The formed benzoyl bromide was oxidized to give the desired
methyl ester after reacting with methanol.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Organic & Biomolecular Chemistry
Page 4 of 4
View Article Online
DOI: 10.1039/C4OB01524J
Chem., 1999, 64, 1191–1196. (h) R. Lerebours and C. Wolf, J. Am.
Chem. Soc., 2006, 128, 13052–13053; (i) L.ꢀL. Wei, L.ꢀM. Wei, W.ꢀ
B. Pan and M.ꢀJ. Wu, Synlett 2004, 1497–1502; (j) C. Liu, J. Wang,
L. Meng, Y. Deng, Y. Li and A. Lei, Angew. Chem. Int. Ed., 2011,
50, 5144–5148; (k) C. Liu, S. Tang, L. Zheng, D. Liu, H. Zhang and
A. Lei, Angew. Chem. Int. Ed., 2012, 51, 5662–5666; (l) S.ꢀI.
Murahashi, T. Naota, K. Ito, Y. Maeda and H. Taki, J. Org. Chem.,
1987, 52, 4319–4327; (m) S. Raiendram and D. C.Trivedi, Synthesis
1995, 153–154; (n) J. Zhao, C. MueckꢀLichtenfeld and A. Studer,
Adv. Synth. Catal., 2013, 355, 1098–1106; (o) R. Grigg, T. R. B.
Mitchell and S. Sutthivaiyakit, Tetrahedron 1981, 37, 4313–4319; (p)
W.ꢀJ. Yoo and C.ꢀJ. Li, Tetrahedron Lett., 2007, 48, 1033–1035; (q)
Y. Zhu and Y. Wei, RSC Adv. 2013, 3, 13668–13670; (r) S. P.
Chavan, S. W. Dantale, C. A. Govande, M. S. Venkatraman and C.
Praveen, Synlett 2002, 267–268; (s) S. Kiyooka, M. Ueno and E.
Ishii, Tetrahedron Lett., 2005, 46, 4639–4642; (t) S.ꢀI. Kiyooka, Y.
Wada, M. Ueno, T. Yokoyama and R. Yokoyama, Tetrahedron 2007,
63, 12695–12701; (u) X.ꢀF. Wu and C. Darcel, Eur. J. Org. Chem.,
2009, 1144–1147; (v) K. Suzuki, T. Yamaguchi, K. Matsushita, C.
Iitsuka, J. Miura, T. Akaogi and H. Ishida, ACS Catal., 2013, 3,
1845–1849; (w) L. Wang, J. Li, W. Dai, Y. Lv, Y. Zhanga and S.
Gao, Green Chem., 2014, 16, 2164–2173; (x) J. Liu, C. Shao, Y.
Zhang, G. Shi and S. Pana, Org. Biomol. Chem., 2014, 12, 2637–
2640; (y) X. –F. Wu, Chem. Eur. J., 2012, 18, 8912–8915; (z) S. C.
Thomason and D. G. Kubler, J. Chem. Educ., 1968, 45, 546.
5
10
15
20
25
30
35
40
45
50
55
4. (a) T. Nobuta, A. Fujiya, S. Hirashima, N. Tada, T. Miura and A. Itoh,
Tetrahedron Lett., 2012, 53, 5306–5308; (b) T. Mohammad, A.
Shaikh, L. Emmanuvel and A. Sudalai, Synth. Commun., 2007, 37,
2641–2646; (c). K. Moriyama, M. Takemura and H. Togo, J. Org.
Chem., 2014, 79, 6094ꢀ6104; (d) N. Mori and H. Togo, Tetrahedron,
2005, 61, 5915ꢀ5925; (e). H. Tohma, T. Maegawa and Y. Kita,
Synlett 2003, 0723ꢀ0725; (f). J. N. Milovanovic, M. Vasojevic and S.
Gojkovic, J. Chem. Soc. Perkin Trans., 1991, 2, 1231–1233;. (g) Y.
Oda, K. Hirano, T. Satoh, S. Kuwabata and M. Miura, Tetrahedron
Lett., 2011, 52, 5392–5394.
5. (a) D. Chandra Mohan, D. Ramachandra Reddy, S. Nageswara Rao and
S. Adimurthy, Adv. Synth. Catal., 2013, 355, 2217–2221; (b) R. D.
Patil and S. Adimurthy, RSC Adv., 2012, 2, 5119–5122; (c) G. Joshi,
R. D. Patil and S. Adimurthy, RSC Adv., 2012, 2, 2235–2239; (d) M.
K. Agrawal, S. Adimurthy and P. K. Ghosh, Synthetic Commun.,
2012, 42, 2931–2936; (e) R. D. Patil and S. Adimurthy, Adv. Synth.
Catal., 2011, 353, 1695–1700; (f) R. D. Patil, G. Joshi and S.
Adimurthy, Ind. Eng. Chem. Res., 2010, 49, 8100–8105; (g) G.
Joshi, S. Bhadra, S. Ghosh, M. K. Agrawal, B. Ganguly, S.
Adimurthy, P. K. Ghosh and B. C. Ranu, Ind. Eng. Chem. Res., 2010,
49, 1236–1241; (h) S. Adimurthy, C. M. Chandi and U. Beifuss, J.
Org. Chem., 2009, 74, 5648–5651.
6. (a) J. J. Orlando and J. B. Burkholder, J. Phys. Chem., 1995, 99, 1143–
1150; (b) R. J. Barnes, M. Lock, J. Coleman and A. J. Sinha, Phys.
Chem., 1996, 100, 453–457; (c) J. S. Francisco, M. R. Hand and I. H.
Williams, J. Phys. Chem., 1996, 100, 9250–9253; (d) T. Ingham, D.
Bauer, J. Landgraf and J. N. Crowley, J. Phys. Chem., A, 1998, 102,
3293–3298.
7. The absorption peak in figure 1a, at 220 nm appears sharp and
maximum may be due to the presence of organic substrate benzyl
alcohol and its derivatives. The individual UVꢀvisible spectra’s for
benzyl alcohol, banzaldehyde and methylbenzoate were provided in the
supporting information.
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]