Palladium-Catalyzed Aerobic Oxidative Carbonylation of C–H Bonds in Phenols for the Synthesis of p-Hydroxybenzoates

Article abstract of DOI:10.1002/ejoc.201800538

This work reports the synthesis of p-hydroxybenzoates directly from phenols by oxidative carbonylation of phenolic C–H bonds, proceding through oxidative iodination. The developed methodology is efficient and economically attractive because phenols are cheap and easily available starting materials. This one-pot strategy was expediently applied to the synthesis of a variety of p-hydroxybenzoates by utilizing simple primary and secondary alcohols with different phenols under mild reaction conditions. Advantageously, the procedure has no need for co-catalysts, co-solvents or external ligands. The utilization of molecular oxygen as a terminal oxidant for C–H bond oxidation represents an additional benefit.

Full text of DOI:10.1002/ejoc.201800538

A Journal of
Accepted Article
Title: Palladium-Catalyzed Aerobic Oxidative Carbonylation of C-H
Bond of Phenol for the Synthesis p-hydroxybenzoate
Authors: Vinayak Vishwas Gaikwad and Bhalchandra Mahadeo
Bhanage
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800538
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800538
Supported by

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
Palladium-Catalyzed Aerobic Oxidative Carbonylation of C-H
Bond of Phenol for the Synthesis p-hydroxybenzoate
Vinayak V. Gaikwad[a] and Bhalchandra M. Bhanage*[a]
Abstract: This work reports the synthesis of p-hydroxybenzoate
directly from phenol by oxidative carbonylation. In this work aryl C-H
bond of phenol was carbonylated via oxidative iodination, leading to
the synthesis of p-hydroxybenzoate. The developed methodology is
efficient and economically attractive because phenols are cheap and
easily available starting material. This novel one-pot strategy has
been expediently applied for the synthesis of variety p-
hydroxybenzoate utilizing simple primary and secondary alcohols
with phenols under mild reaction condition. Advantageously, this
reaction proceeded without the need of co-catalyst, co-solvent and
external ligand. Utilization of molecular oxygen as a terminal oxidant
for oxidation of C-H bond is an additional benefit of this strategy.
Scheme 1.. Synthesis of p-hydroxybenzoate by Carbonylation method.
Introduction
oxygen as an ideal and readily available, nonhazardous oxidant
in oxidative carbonylation reactions. [28–30]
Transition metal catalyzed carbonylation of aryl halides or
p-hydroxybenzoate is a major chemical feedstock in the
research field of natural products, pharmaceuticals,
agrochemicals and functional materials.[31–36] In the past decade,
significant attention has been made towards the synthesis of
these carbonylative compounds by the traditional approach.[37–41]
Among these, palladium catalyzed carbonylation of p-iodophenol
was followed by nucleophilic attack of alcohols leads to the
synthesis of p-hydroxybenzoate is one of the dominant route
used in the laboratory as well as an industrial scale (Path I).[42–45]
Recently, Elango and co-workers have successfully synthesized
p-hydroxybenzoate by activation of bromophenol using
carbonylation method.[46] However, those methodologies have
some limitations such as the use of expensive starting materials,
longer reaction time, harsh reaction conditions, uses of
traditional solvents, co-catalyst and lewis acids. Thus, to
overcome these limitations we report here the synthesis of p-
hydroxybenzoate directly from phenol.
Herein, we communicate a palladium catalyzed carbonylation of
aryl C-H bond of phenol for the synthesis of p-hydroxybenzoate
as an efficient approach (path II). In this context, carbonylation
occurs selectively at the para position of phenol by activation of
aryl C-H bond via oxidative iodination. Additionally, the
advantage of this methodology is a single step process, utilizing
molecular oxygen as an ideal and environmentally benign
oxidant.
pseudohalides has been a most potent methodology for the
synthesis of carboxylic acid and its derivatives and this method
was established in 1974 by Heck and co-workers.[1–8] On the
other hand, activation of the inert C-H bond is very attractive and
difficult task in synthetic chemistry, however with a precise
selection of catalyst and substrate the task can be achieved.[9–12]
Even so, carbonylation of C-H bond has a great challenge and
attractive field. Synthesized benzoic acid by carbonylation of aryl
C-H bond was pioneered by Fujiwara and co-workers in 1980.[13]
In past two decades, the significant efforts have been made
towards broadening the scope of carbonylation reaction via C-H
bond activation. These reactions are environmentally benign and
greener, as it avoids multiple steps for functionalization of such
substrates.
Palladium-catalyzed
carbonylation
of
C-H
functionalization of arenes and heteroarenes are shown for the
synthesis of carboxylic acids and their derivatives.[14–19]
Nowadays, Directing group-assisted carbonylation of the simple
C-H bond has been emerged as an ideal strategy by introducing
of carbon monoxide to construct variety carbonylative
compounds. Numerous, directing groups such as amide, amines,
heteroatoms and hydroxy groups have been used for
carbonylation of C-H bond.[20–27] However, most of this progress
is practiced by molecules containing directing groups, utilizing
hazardous metals and oxidant such as copper, silver salt or
peroxide which are undesirable from a green chemistry point of
view. Molecular
Results and Discussion
[a]
Department of Chemistry, Institute of Chemical Technology,
Mumbai, 400 019, India. E-mail: bm.bhanage@ictmumbai.edu.in;
bm.bhanage@gmail.com; Fax: +91 22 33611020; Tel: +91 22
3361 2601
The carbonylative coupling between phenol and methanol for
the synthesis of methyl 4-hydroxybenzoate was selected as a
model reaction. Various reactions parameters have been
screened on this model reaction (Table1). Initially, we
investigate various palladium precursors for the carbonylative
† Electronic supplementary information (ESI) available; (Study of
time, temp.and press, copies of 1H and13C NMR)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
Table 1: Screening of optimal reaction condition[a]
Entry
Pd precursor
Oxidant
Additive
Base
Solvent
Conversion[b] (%)
Selectivity[b] p:o (%)
1
2
Pd(OAc)2
O2
O2
KI
KI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
NaOH
KOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
CH3CN
DMF
80
79
80
98
--
85:15
80:20
68:32
93:7
--
PdCl2
3
Pd(PPh3)4
O2
KI
4
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
O2
KI
5
Ag2O
Cu (OAc)2
Oxone
K2S2O8
O2
KI
6
KI
--
--
7
KI
--
--
8
KI
--
--
9
TBAI
NaI
NH4I
I2
80
70
55
30
30
25
17
--
85:15
65:35
60:40
63:37
70:30
65:35
60:40
--
10
11
12
13C
14C
15C
16C
17
18
19
20
21
22
O2
O2
O2
O2
KI
O2
KI
O2
KI
THF
O2
KI
Toluene
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
O2
KI
78
80
75
72
60
50
60
55
80:20
83:17
65:35
62:37
60:40
55:45
75:25
69:31
O2
KI
O2
KI
O2
KI
O2
KI
NEt3
O2
KI
DBU
d
23
O2
KI
K2CO3
K2CO3
e
24
O2
KI
[a]Reaction conditions: Phenol (1 mmol), base (1.5 mmol), MeOH (10 mL), additive (1.5 mmol), catalyst (2 mol %), CO:O2 (7:1), 8 bar, 100 oC, 18 h [b]Conversion
and selectivity determined by GC &GC-MS. [c]MeOH (5 mL) and solvent (5 mL).[d] PPh3 (5 mol %) [e] Xantphose (5 mol %)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
coupling between phenol with methanol in presence of CO:O2
(7+1=8 bar) mixture. We used molecular oxygen as a
terminal oxidant along with KI for 18 h at 100oC. Initially, we
used Pd(OAc)2 as a catalyst precursor and observed
carbonylative product of methyl 4-hydroxybenzoate (p) and
methyl 2-hydroxybenzoate (o) with 80% conversion of 1 and
showing 85:15% selectivity. (Table 1 entry 1). However, the
selectivity of p:o was decreased to 80:20% and 68:32% at
80% conversion by using PdCl2 and Pd(PPh3)4 as a catalyst
respectively (Table 1 entry 2 and 3). Next, we obtained 93:7%
selectivity of p:o with 98% conversion by using PdCl2(PPh3)2
as an effective catalyst. Since, this catalyst furnished higher
conversion, we used this catalyst for further studies. (Table 1,
entry 4). Further, we screened various commercial oxidants
such as Ag2O, Cu(OAc)2, Oxone and K2S2O8 to see the effect
on conversion and selectivity. Molecular oxygen was the only
oxidant which gave a better conversion of 1 (Table 1, entries
5-8) and was used for the next optimization study.
Furthermore, we investigated PdCl2(PPh3)2 catalyst along
with different additives to increase the selectivity of the
desired ester of 2. We have carried out the reaction by using
various additives such as TBAI, NaI, NH4I and I2 and it gave
p:o selectivity of 85:15%, 65:35%, 60:40 % and 63:37%
respectively (Table 1, entries 9-12). The highest conversion
as well as selectivity was obtained by using of KI as an
additive and further reactions were carried out with it.
Subsequently, the effect of various solvents was investigated.
We observed 98% conversion of 1 by using methanol as a
solvent. However, methanol is good solvent and it also acts
as an effective nucleophile and hence considered for the next
optimization studies (Table 1 entry 13-16). The conversion of
1 was significantly increased by using of K2CO3 as a base
and it furnished good selectivity ratio of p:o product, while
other inorganic bases such as Na2CO3, Cs2CO3, NaOH and
KOH reduces conversion and selectivity (Table 1 entries 17-
20). Organic bases such as NEt3 and DBU provides 60% and
50% conversion of 1 with poor selectivity (Table 1 entries 21
and 22). Further, we extended this work for the study of
various phosphorous containing ligands along with
PdCl2(PPh3)2 as a catalyst, and we have detected 60%
conversion of 1 with PPh3 as a ligand. Next, the conversion
was declined to 55%, when the reaction was carried along
Xantphos as a ligand with good selectivity i.e. the negligible
effect of ligands on the conversion and selectivity of
carbonylation reaction. The used of additional ligands was not
observed in the carbonylative reaction. (Table 1 entries 23
and 24). Further, we studied the effect of CO pressure on the
reaction. We observed the superior conversion of 1 by
applying CO:O2 (7:1 bar) pressure with showing good
selectivity ratio (93:7%). However, a decrease in CO:O2
pressure (5:1 bar), led to decrease in conversion (80%) and
selectivity (see ESI, Table 1, entry 1-3). Further, we study the
effect of temperature on conversion as well as selectivity. The
Table 2. Substrate scope of Phenol[a]
o
o
increase in the temperature from 100 C to 120 C has not a
significant effect on conversion and selectivity. Next, we
observed 95% conversion, when the reaction was carried out
80 oC for 18h. (see ESI Table 1, entry 4-6). Time study
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
Scheme 2: Controlling experiment[a]
[a]Reaction conditions: Phenol (1 mmol), base (1.5 mmol), MeOH (10
mL), additive (1.5 mmol), catalyst (2 mol %), CO:O2 (7:1 bar), 18 h.
Isolated Yield.
Entry No
Variation from std condition
Yield [b] (%)
[
b]
1
2
3
4
No PdCl2(PPh3)2
2 (95),
3 (0)
revealed that 18h was enough for good conversion (98%) and
selectivity of the desired ester (see ESI Table 1, entry 7-9).
After optimization of reaction conditions, we further
investigated the synthesis of the various ester from a range of
substituted phenols with alcohols. Methylparaben and
ethylparaben are major backbones of pharmaceutically active
drug molecules and it is considered as very important in
medicinal chemistry. We have successfully synthesized those
compounds by carbonylative reaction between phenol with
methanol and ethanol underdeveloped condition, providing
75% (2a) and 74% (2b) yield and a trace amount of ortho
product respectively. However, secondary alcohol such as
isopropanol (IPA) reacted with phenol and generated 63%
yield of 2c and very negligible ortho product. Next, we
proceeded reaction between ortho-cresol with methanol and
ethanol which led to the synthesis of 2d and 2e in 76% and
74% yield respectively. Furthermore, we were successfully
able to synthesize methyl 4-hydroxy-2-methyl benzoate (2f)
and ethyl 4-hydroxy-2-methyl benzoate (2g) by carbonylative
coupling between m-cresol with methanol and ethanol offered
in excellent yield. When IPA reacted with meta-cresol, the
steric crowing between methyl groups of alcohols and m-
cresol led to decrease in yield of desired ester 2h. Further,
the phenol bearing the strong electron donating group (-OMe),
carbonylative coupling with methanol and ethanol offered the
corresponding ester 2i and 2j, 2k with excellent yield. Next,
we proceeded reaction with propanol and moderate yields of
respected ester (2l) were observed. Next, we carried out the
reaction of methanol with electron withdrawing substituents,
meta-nitro, meta- fluoro on phenol, but no little product of 2m
and 2n was observed. Next, we proceed reaction of p-cresol
with methanol, unfortunately, reaction failed to the product of
2l in 0 % yield. To gain inside the mechanism we have
carried out the controlled experiments by carbonylative
coupling between phenol and methanol under different
conditions. Without the use of an active catalyst, the reaction
proceeded with no ester product 3 observed showing that
active catalyst have a major role in the reaction (Scheme 2
entry 1). Next, we got 4-iodophenol in 90% yield, without
applying of carbon monoxide pressure, this result clearly
indicates that formation of 4-iodophenol as an intermediary in
carbonylative transformation (Scheme 2 entry 2). Further, we
remove KI from standard condition and reaction proceeded
with 0% yield of 2 and 3. These results indicate that
molecular oxygen has a very crucial role for activation of C-H
bond, as the yield of product 3 drastically reduced to 10%
No CO
No KI
2 (90),
3 (0)
2 (0),
3 (0)
Without O2
2 (15),
3 (10)
[a]Reaction conditions: Phenol (1 mmol), base (1.5 mmol), MeOH (10
mL), additive (1.5 mmol), catalyst (2 mol %), CO:O2 (7:1, bar). [b] Isolated
Yield
when reaction proceeded without oxidant (Scheme 2 entries
3 and 4). On the basis of obtained results and previous
literature survey [47], we have proposed the plausible reaction
mechanism in Scheme 3. In the first step, molecular oxygen
oxidizes the KI and release iodine, subsequently, iodination
occurs at the para position of phenol by aryl C-H bond
activation to form of species A (1H NMR spectrum of Isolated
intermediate shown in ESI). Next, Pd (II) insert between RX
bond and formation of aryl palladium species B take place.
Next, CO coordinates with aryl palladium species to the
Scheme 3: Plausible reaction mechanism of esterification of Phenol.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
formation of species C. Then the nucleophilic attack of
alcohol on species C to offered p-hydroxybenzoate via
reductive elimination of palladium metal.
Acknowledgement
Auther Vinayak V. Gaikwad gratefully acknowledge to Council
of Scientific & Industrial Research (CSIR) New Delhi, India for
providing Senior Research Fellowship (SRF).
Conclusion
In summary, we have developed a simple and effective
protocol for the synthesis of valuable p-hydroxy benzoate
directly from phenol. Developed methodology received a lot
of attention as highly enviable and attractive access for
inserting carbonyl moiety on account of its high atom and
step economy. In this context carbonylation of aryl C-H bond
via oxidative iodination followed by nucleophilic attack of
alcohols leading to the synthesis of p-hydroxybenzoate.
Keywords: Aerobic Oxidation; Carbonylation; C-H Activation;
Phenol; p-Hydroxybenzoate
[1]
A. Schoenberg, I. Bartoletti, R. F. Heck, J. Org. Chem. 1974, 39,
3318–3326.
[2]
[3]
P. Gautam, B. M. Bhanage, Chemistry Select 2016, 1, 5463–5470.
P. Gautam, R. Gupta, B. M. Bhanage, European J. Org. Chem.
2017, 2017, 3431–3437.
[4]
K. Dong, R. Sang, J. Liu, R. Razzaq, R. Franke, R. Jackstell, M.
Beller, Angew. Chemie - Int. Ed. 2017, 56, 6203–6207.
R. S. Mane, B. M. Bhanage, J. Org. Chem. 2016, 81, 1223–1228.
R. S. Mane, B. M. Bhanage, Adv. Synth. Catal. 2017, 359, 2621–
2629.
Compared to previous reports,
this methodology
demonstrates one spot synthesis and good selectivity
towards the para C-H bond activation. This methodology
does not require external ligands, co-catalysts and co-
solvents. Molecular oxygen as an ideal and cheap as well as
green oxidant. The new strategy generates 4-iodophenol
intermediate and it opens the access for the synthesis of a
variety of compounds directly from phenol.
[5]
[6]
[7]
[8]
[9]
Y. Wang, X. Yang, C. Zhang, J. Yu, J. Liu, C. Xia, Adv. Synth. Catal.
2014, 356, 2539–2546.
M. Beller, D. M. Cartney, P. J. Guiry, Chem. Soc. Rev. 2011, 40,
4877–5208.
L. Ackermann, Chem. Rev. 2011, 111, 1315–1345.
[10] W. R. Gutekunst, P. S. Baran, Chem. Soc. Rev. 2011, 40, 1976.
[11] M.-L. Louillat, F. W. Patureau, Chem. Soc. Rev. 2014, 43, 901–910.
[12] Y. Yang, J. Lan, J. You, Chem. Rev. 2017, 117, 8787–8863.
[13] Y. Fujiwara, T. Kawauchi, H. Taniguchi, J. Chem. Soc. Chem.
Commun. 1980, 220.
Experimental Section
All chemicals purchased from Sigma Aldrich, Alfa Asear, Wako
chemicals, S.D. fine and used without further purification. All
dehydrated solvents were purchased advent chemical Mumbai. The
CO gas cylinder purchased from Rakhangi gas services, Mumbai.
[14] X. F. Wu, P. Anbarasan, H. Neumann, M. Beller, Angew. Chemie -
Int. Ed. 2010, 49, 7316–7319.
[15] S. T. Gadge, P. Gautam, B. M. Bhanage, Chem. Rec. 2016, 16,
835–856.
General procedure for synthesis of ester from Phenol
[16] P. Gautam, B. M. Bhanage, Chapter
6 - Palladium-Catalyzed
Carbonylative and Carboxylative {CH} Functionalization Reactions:
Importance and Role of Regioselectivity, Elsevier Inc., 2017.
[17] Q. Liu, H. Zhang, A. Lei, Angew. Chemie - Int. Ed. 2011, 50, 10788–
10799.
Phenol (1 mmol), alcohol (10 mL), PdCl2(PPh3)2 catalyst (2 mol %),
and K2CO3 (1.5 mmol) were added to 100 mL stainless steel
autoclave. The reactor was closed and flushed with CO gas for three
times. Then autoclave pressurized with CO:O2 (7:1, bar) at 100oC.
The reaction mixture stirred with a mechanical stirrer (450 rpm) for
18h. After completion of the reaction, the autoclave was cooled to
room temperature and the pressure was carefully released and the
reactor opened. The crude organic product was extracted with ethyl
acetate two times (20 mL each) and it evaporates under vacuum. The
obtained crude product was confirmed by GC-MS and thin layer
chromatography using Merck silica gel 60 F254 plates and it detect
using 254 nm UV lamp. The product was purified by use of column
chromatography on a silica gel 100-200 mesh (Flow rate 2 mL/min).
The yield of product calculates by using a Perkin Elmer Clarus 400
Gas Chromatography with Flame ionization detector (FID) and
capillary column (30 m × 0.25 mm × 0.25 μm). 1H spectra were
recorded on 400 MHz and 500 MHz spectrometer and product
dissolved in CDCl3 with TMS as an internal standard. 13C were
recorded on 101 MHz and 126 MHz spectrometer using CDCl3
solvent. The chemical shift was recorded in part per million (ppm) with
respect to TMS and coupling constant measured in Hertz. The
splitting patterns were described as s (singlet), d (doublet), dd
(doublet of doublet), t (triplet) and m (multiplate).
[18] Y. Wu, C. Jiang, D. Wu, Q. Gu, Z. Y. Luo, H. B. Luo, Chem
Commun 2016, 52, 1286–1289.
[19] J.-C. Xiang, Y. Cheng, M. Wang, Y.-D. Wu, A.-X. Wu, Org. Lett.
2016, 18, 4360–4363.
[20] P. L. Wang, Y. Li, L. Ma, C. G. Luo, Z. Y. Wang, Q. Lan, X. S. Wang,
Adv. Synth. Catal. 2016, 358, 1048–1053.
[21] Z. Wang, Y. Li, F. Zhu, X. F. Wu, Adv. Synth. Catal. 2016, 358,
2855–2859.
[22] M. Chen, Z. H. Ren, Y. Y. Wang, Z. H. Guan, J. Org. Chem. 2015,
80, 1258–1263.
[23] X. Zhang, S. Dong, X. Niu, Z. Li, X. Fan, G. Zhang, Org. Lett. 2016,
18, 4634–4637.
[24] W. Li, Z. Duan, R. Jiang, A. Lei, Org. Lett. 2015, 17, 1397–1400.
[25] V. Rajeshkumar, T.-H. Lee, S.-C. Chuang, Org. Lett. 2013, 15,
1468–1471.
[26] K. Inamoto, J. Kadokawa, Y. Kondo, Org. Lett. 2013, 15, 3962–
3965.
[27] F. Ling, C. Ai, Y. Lv, W. Zhong, Adv. Synth. Catal. 2017, 359, 3707–
3712.
[28] B. Haffemayer, M. Gulias, M. J. Gaunt, Chem. Sci. 2011, 2, 312–
315.
[29] R. Shi, L. Lu, H. Zhang, B. Chen, Y. Sha, C. Liu, A. Lei, Angew.
Chemie Int. Ed. 2013, 52, 10582–10585.
[30] H. Zhang, D. Liu, C. Chen, C. Liu, A. Lei, Chem. - A Eur. J. 2011, 17,
9581–9585.
[31] F. A. Andersen, Int. J. Toxicol. 2008, 27, 1–82.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
[32] A. Fonseca, F. Ana, F. A. Paula, Int. j. med. res. pharm. sci., 2016,
3, 1–11.
[33] J. A. Ocaña-González, M. Villar-Navarro, M. Ramos-Payán, R.
Fernández-Torres, M. A. Bello-López, Anal. Chim. Acta 2015, 858,
1–15.
[34] D. Błędzka, J. Gromadzińska, W. Wąsowicz, Environ. Int. 2014, 67,
27–42.
[35] C. Moreta, M. T. Tena, K. Kannan, Environ. Res. 2015, 142, 452–
460.
[36] M. Yegambaram, B. Manivannan, T. G. Beach, R. U. Halden, Curr.
Alzheimer Res. 2015, 12, 116–146.
[37] R. Gopinath, B. Barkakaty, B. Talukdar, B. K. Patel, J. Org. Chem.
2003, 68, 2944–2947.
[38] W. Guo, J. Li, N. Fan, W. Wu, P. Zhou, C. Xia, Synth. Commun.
2005, 35, 145–152.
[39] R. K. Sharma, S. Gulati, J. Mol. Catal. A Chem. 2012, 363–364,
291–303.
[40] H. Yu, C. Liu, X. Dai, J. Wang, J. Qiu, Tetrahedron 2017, 73, 3031–
3035.
[41] M. Caporaso, G. Cravotto, S. Georgakopoulos, G. Heropoulos, K.
Martina, S. Tagliapietra, Beilstein J. Org. Chem. 2014, 10, 1454–
1461.
[42] S. Antebi, P. Arya, L. E. Manzer, H. Alper, J. Org. Chem. 2002, 67,
6623–6631.
[43] M. V. Khedkar, T. Sasaki, B. M. Bhanage, ACS Catal. 2013, 3, 287–
293.
[44] R. S. Mane, T. Sasaki, B. M. Bhanage, RSC Adv. 2015, 5, 94776–
94785.
[45] H. Urata, H. Maekawa, S. Takahashi, T. Fuchikami, J. Org. Chem.
1991, 56, 4320–4322.
[46] P. Baburajan, R. Senthilkumaran, K. P. Elango, New J. Chem. 2013,
37, 3050.
[47] K. Rajender Reddy, M. Venkateshwar, C. Uma Maheswari, P.
Santhosh Kumar, Tetrahedron Lett. 2010, 51, 2170–2173.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800538
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
Key Topic*
Vinayak V. Gaikwad[a] and Bhalchandra
M. Bhanage*[a]
Page No. – Page No.
Title: Palladium-Catalyzed Aerobic
Oxidative Carbonylation of C-H Bond
of Phenol for the Synthesis of p-
hydroxybenzoate
Text for Table of Contents
Oxidative Carbonylation, C-H bond activation
This article is protected by copyright. All rights reserved.