Temperature-controlled acyloxylations and hydroxylations of bromoarene by a silver salt

Article abstract of DOI:10.1016/j.tetlet.2016.01.022

Temperature-controlled selective acyloxylations and hydroxylations of bromoarene were achieved using a silver salt. Various aryl esters were synthesized at 100°C, and the hydroxylated arene was obtained at 150°C from silver-mediated conditions. Mechanistically, a two-step acyloxylation-hydrolysis pathway was revealed for hydroxylation of bromoarene.

Full text of DOI:10.1016/j.tetlet.2016.01.022

Tetrahedron Letters 57 (2016) 781–783
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Temperature-controlled acyloxylations and hydroxylations
of bromoarene by a silver salt
Kwangho Yoo a,b, Hyojin Park a, Suyeon Kim a,b, Min Kim a,b,
⇑
a Department of Chemistry, Chungbuk National University, 1 Chungdae-ro, Seowon-gu, Cheongju-si, Chungbuk 28644, Republic of Korea
b Research Team for Syntheses and Physical Properties of Various Molecules (BK21Plus), Chungbuk National University, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Temperature-controlled selective acyloxylations and hydroxylations of bromoarene were achieved using
a silver salt. Various aryl esters were synthesized at 100 °C, and the hydroxylated arene was obtained at
150 °C from silver-mediated conditions. Mechanistically, a two-step acyloxylation–hydrolysis pathway
was revealed for hydroxylation of bromoarene.
Received 16 November 2015
Revised 30 December 2015
Accepted 7 January 2016
Available online 7 January 2016
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Silver
Acyloxylation
Hydroxylation
Carboxylation
The carboxylic ester is a fundamental functional group used in
organic synthesis, pharmaceutical molecules, and material
sciences.1,2 Esters are prepared via direct reactions with carboxylic
acids and alcohols. However, harsh conditions are required for this
traditional method due to the low nucleophilicity of carboxylic
acids. Various activated intermediates or catalytic conditions have
been studied for the synthesis of esters from carboxylic acids and
alcohols, including Mitsunobu-type azopyridine catalysts3 and iron
catalysts.4 In addition, different types of coupling partners have
been developed. The coupling reaction between carboxylic acids
and aryl boronic acid molecules were first studied with copper-cat-
alyzed Chan-Lam reactions.5 The diaryliodonium salt was also used
for the O-arylation of carboxylic acids. Olofsson and co-workers
contributed significantly in this field, using metal-free coupling
reactions in mild reaction conditions.6 Aryl halides are also good
reaction partners for the synthesis of aryl esters with the carboxy-
late anion functioning as a nucleophile to attack the carbon–halo-
gen bond. Several catalytic conditions have been studied for this
acyloxylation.7 Lastly, acyloxylation through the sp2 C–H bond
activation has been extensively studied using various precious late
transition metals.8 Herein, we present silver-mediated acyloxyla-
tion and hydroxylation of a bromoarene molecule, which is con-
trolled by temperature. Various aryl esters and 10-hydroxy benzo
[h]quinoline are selectively synthesized from 10-brombenzo[h]
quinoline with moderate to high yields.
We started our investigations with 10-bromobenzo[h]quinoline
(1) as the model substrate, and it reacted with benzoic acid in the
presence of various silver salts, bases, and solvents (Table 1). No
reactivity was observed with various silver salts such as silver acet-
ate, silver chloride, silver cyanide, and silver hexafluorophosphate
(Table 1, entries 1–4). However, silver carbonate in the presence of
potassium fluoride provided increased reactivity (entry 5). Among
the various alkali fluorides, lithium fluoride and potassium fluoride
displayed good yields for benzo[h]quinoline-10-yl-benzoate (3a)
(Table 1, entries 5–9). In addition, the usage of potassium carbon-
ate showed moderate yield (Table 1, entry 10), and not surprisingly
the absence of either the silver salt or base resulted in no conver-
sion for benzoxylation (Table 1, entries 11 and 12). Non-polar aro-
matic solvents showed moderate yields, and among them benzene
provided the best result (entries 13 and 14). Lastly, the combina-
tion of silver fluoride and potassium carbonate displayed lower
yields than the original combination of silver carbonate and potas-
sium fluoride (entry 15). Finally, by replacing the combination of
benzoic acid and silver carbonate to only silver benzoate, only
39% yield of 3a was observed.
Under the optimized reaction conditions, a range of carboxylic
acids were tested with 10-bromobenzo[h]quinoline (1, Scheme 1).
Interestingly, the steric hindrance of carboxylic acids did not dimin-
ish the reactivity of acyloxylation. For example, 2-methylbenzoic
acid (e.g., o-toluic acid) showed better yield than p-toluic acid (3b
for 79% and 3d for 16% in Scheme 1). Additionally, other ortho-sub-
stituted benzoic acids (MeO, Cl, and Br series) showed better yield
than para-substituted benzoic acids for the acyloxylation of 1
⇑
Corresponding author. Tel.: +82 43 261 2283; fax: +82 43 267 2279.
E-mail address: minkim@chungbuk.ac.kr (M. Kim).
http://dx.doi.org/10.1016/j.tetlet.2016.01.022
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.

782
K. Yoo et al. / Tetrahedron Letters 57 (2016) 781–783
Table 1
bromopolyarene substrates such as 1- or 2-bromonaphthalenes,
Catalytic condition screening for acyloxylationa
9-bromoanthracene, and 9-bromophenanthrene. Again these pol-
yaromatic compounds showed no reactivity with this silver sys-
tem. Thus, we assumed the combination of a pyridine metal
binding group and the distinct electronic environment of benzo
[h]quinoline lead to the good reactivity for acyloxylation using this
silver system.
O
OH
Ag salt (2 equiv.)
base (1 equiv.)
N
+
N
O
O
solvent,100 oC, 24 h
Br
During our further investigations for acyloxylation, 10-hydrox-
ybenzo[h]quinoline (4) was obtained as a major product when the
reaction temperature was elevated (Table S1). When the reaction
solvent was changed to p-xylene, due to the higher boiling point,
only the hydroxylation of aryl bromide was observed using the
combination of silver carbonate and potassium fluoride at 150 °C
(Table 2). Recently, the synthesis of hydroxylated arenes has been
observed using various transition metals.10 Although palladium,
copper, and iron catalysts have been widely studied for the hydrox-
ylation of haloarenes, silver-mediated hydroxylation has not been
reported to date. The reactivity of para-substituted benzoic acids
showed slightly lower reactivities than ortho-substituted sub-
strates, and similar trends were observed in the substrate scope
tests (entries 1–6, Table 2). Interestingly, the aliphatic carboxylic
acid, pivalic acid (e.g., 2,2,2-trimehtylacetic acid) displayed the
best conversion for hydroxylation; thus reaction temperature
could be decreased to 135 °C with good yield for 4 (95%, entry 7).
We began our mechanistic investigations with a 1H NMR time
study to observe reaction intermediates. At 3 h and 6 h, the
3a
1
2a
Entry
Silver salt
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
AgOAc
AgCl
AgCN
KF
KF
KF
KF
KF
LiF
NaF
RbF
CsF
K2CO3
KF
—
KF
KF
K2CO3
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Benzene
Toluene
p-Xylene
Benzene
<1%
<1%
<1%
<1%
75
75
32
55
35
AgPF6
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
9
10
11
12
13
14
15
57
<1%
<1%
62
55
44
Ag2CO3
Ag2CO3
Ag2CO3
AgF
a
The reaction of 10-bromobenzo[h]quinoline (1, 0.15 mmol) with benzoic acid
(2a, 0.3 mmol) was carried out in a specified solvent (0.5 mL) in the presence of
silver salt (0.3 mmol) and base (0.15 mmol) at 100 °C for 24 h.
b
Yield of isolated product is reported as an average number from at least two
independent measurements.
Ag2CO3 (2 equiv.)
(Scheme 1).9 Both electron-withdrawing and -donating groups sub-
stituted in ortho-position of benzoic acid displayed moderate to
good yields (3b for 79%, 3e for 64%, 3h for 73%, 3k for 74%). During
our investigations in this substrate scope, we found solubility issues
when low yields were obtained. Some benzoic acids, including para-
substituted benzoic acids, remained in a solid form after the reac-
tion. Since benzoic acids are generally not highly soluble organic
molecules in common non-polar aromatic solvents, aprotic polar
solvents were tested. Although N,N-dimethylformamide (DMF)
allowed for greater solubility, the mixture of benzene and DMF
was the best combination for the acyloxylation yields. Overall, the
yields of non- or less- reactivity benzoic acids were enhanced 2–
10 times (Scheme 1, Condition B, benzene/DMF, 1:3, v/v ratio).9
For examples, the yield of 3d from p-toluic acid was increased from
16% to 66%, and 3g was improved 10 times (from p-anisic acid) in
the condition B. Lastly, the reactivity of aliphatic and conjugated
carboxylic acids was investigated. Although the simplest, acetic acid
showed no conversion, hexanoic acid and trans-cinnamic acid
showed the acyloxylation product with very low yields in benzene
(3n and 3o). In addition, for pivalic acid, the selective conversion
for the acyloxylation occurred at a lower temperature (80 °C) than
the optimized condition (100 °C), and a low yield for the acyloxy-
lated product (3p) was obtained. It was also found that the ben-
zene–DMF mixture solvent enhanced the product yields in the
case of long aliphatic chains and conjugated carboxylic acids (3n
and 3o).
O
KF (1 equiv.)
N
+
HO
R
benzene,100 oC, 24 h
N
N
O
O
Br
R
1
2
3
N
N
N
O
O
O
O
O
O
Me
O
O
Me
OMe
Me
3b, 79%
3c, 88%
3e, 64%
3d, 16%
3d, 66%a
N
N
N
N
O
O
O
O
O
O
MeO
O
O
MeO
Cl
Cl
3h, 73%
3f, 26%
3g, 5%
3i, 29%
3f, 82%a
3g, 51%a
3i, 70%a
N
N
N
N
O
O
O
O
O
O
O
Cl
Br
O
Br
Br
3k, 74%
3j, 15%
3l, 38%
3m, 17%
3j, 50%a
3I, 68%a
3m, 55%a
The scope of the reaction of aryl halides and benzoic acids was
then examined. An aryl chloride, 10-chlorobenzo[h]quinoline
showed no reactivity using this silver-mediated system. Pyridyl-
containing compounds 2-(2-bromophenyl)pyridine and 2-(2,6-
dibromophenyl)pyridine were tested for acyloxylation, and dis-
played poor conversion under the present system. In addition to
the pyridyl group, furan and thiophene moieties (e.g., 2-(2-bro-
mophenyl)furan and 2-(2-bromophenyl)thiophene) showed no
reactivity in the present system. In fact, only 10-bromobenzo[h]
quinoline showed reactivity for this system. We also tested
N
N
N
O
O
O
O
O
O
3n, 11%
3o, <5%
3p, 36%b
3n, 55%a
3o, 21%a
Scheme 1. Carboxylic acid substrate scopes for acyloxylation.9

K. Yoo et al. / Tetrahedron Letters 57 (2016) 781–783
783
Table 2
ideal. In 2013 Martin and coworkers reported a two-step copper-
catalyzed benzoxylation and hydrolysis pathway on their system.8e
For the present system, the two reactions are controlled by
temperature. The lower temperature of 100 °C, only prompted the
acyloxylation by the silver salt, and for the higher temperature
(150 °C) the hydrolysis of ester is observed.
In summary, we have described temperature-controlled acy-
loxylations and hydroxylations of 10-bromobenzo[h]quinoline by
silver salts. The reaction types and products are altered simply
by changing the reaction temperature between 100 °C and 150 °C
and the solvent. For our mechanistic studies, the hydroxyl com-
pound was synthesized from the hydroxylation of the acyloxylated
intermediate in silver-mediated condition. Synthetic applications
of the present methodology are underway, which will be reported
in due course.
Silver-mediated hydroxylation of 10-bromobenzo[h]quinolinea
Ag2CO3 (1.1 equiv.)
KF (1 equiv.)
O
+
H
O
R
N
N
p-xylene,150 oC, 24 h
Br
H
4
O
1
2
Entry
Carboxylic acids
Yieldb (%)
1
2
3
4
5
6
7
2-Methylbenzoic acid
3-Methylbenzoic acid
4-Methylbenzoic acid
2-Bromobenzoic acid
3-Bromobenzoic acid
4-Bromobenzoic acid
Pivalic acid
95
93
83c
95
93
82c
95d
a
The reaction of 10-bromobenzo[h]quinoline (1, 0.15 mmol) with carboxylic acid
Acknowledgments
(2, 0.3 mmol) was carried out in p-xylene (0.5 mL) in the presence of silver car-
bonate (0.165 mmol) and potassium fluoride (0.15 mmol) at 150 °C for 24 h.
b
Yield of isolated product is reported as an average number from at least two
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by
the Ministry of Science, ICT & Future Planning (2013R1A1A1061399)
and the Creative Human Resource Training Project for Regional
Innovation through NRF funded by the Ministry of Education
(2014H1C1A1066874).
independent measurements.
c
1H NMR yield using anisole as a internal standard.
Reaction was performed at 135 °C.
d
HO
O
Ag2CO3
KF
150 o
C
Ag2CO3
KF
+
Me
Supplementary data
N
N
N
O
O
H
O
Br
100 o
C
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2016.01.
022.
2b
3b
1
Me
N
4, 95%
2-MeBzOH
Ag2CO3
References and notes
N
KF
O
H
O
p-xylene
1. Otera, J. Esterification Methods, Reactions and Applications; Wiley-VCH:
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2. (a) Franklin, A. S. J. Chem. Soc., Perkin Trans. 1 1998, 2451; (b) Franklin, A. S. J.
Chem. Soc., Perkin Trans. 1 1999, 3537.
150 o
C
Replacing 2-MeBzOH
to H2O: no reaction
O
Me
4, 99%
3b
3. Iranpoor, N.; Firouzabadi, H.; Khalili, D.; Motevalli, S. J. Org. Chem. 2008, 73,
4882.
Scheme 2. The
bromobenzo[h]quinoline.
2 step pathways for acyloxylation and hydroxylation of 10-
4. Taniguchi, T.; Hirose, D.; Ishibashi, H. ACS Catal. 2011, 1, 1469.
5. Zhang, L.; Zhang, G.; Zhang, M.; Cheng, J. J. Org. Chem. 2010, 75, 7472.
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9. Typical procedure: The reaction of 10-bromobenzo[h]quinoline (1, 0.15 mmol)
with carboxylic acid (2, 0.3 mmol) was carried out in a specified solvent
(0.5 mL) in the presence of silver carbonate (0.3 mmol) and potassium fluoride
(0.15 mmol) at 100 °C for 24 h. Yields of isolated product are reported as an
average number from at least two independent measurements. aCondition B:
benzene/DMF (1/3; v/v ratio) mixture was used as a solvent (0.5 mL). bReaction
was performed at 80 °C.
significant CH3 peak of acyloxylated compound 3b was observed.
The ratio between intermediate (3b)/final product (4) was 6:4 at
6 h. This ratio decreases over time with a ratio of 1:9 (3b:4) observed
at 12 h. In the case of 2-methylbenzoic acid, the hydroxylation was
complete at 18 h (Fig. S1 in Supporting information for detail). The
kinetic NMR study suggests that acyloxylation is accelerated at high
temperatures (150 °C), with benzo[h]quinoline fully converted to
the acyloxylated product 3b within 12 h (24 h was required at
100 °C for full conversion), and the hydrolysis of ester only occurred
at 150 °C. In addition, when thereaction occurred with isolated com-
pound 3b, nearly quantitative isolated yield (99% of 4) was observed
under the optimized conditions along with 1.1 equiv of 2-methyl-
benzoic acid. This hydrolysis step could not be performed in case
of water additives. The remaining benzoic acids and recovered ben-
zoate from 3b could accelerate the hydrolysis step (Scheme 2).
Finally, these findings support that a two-step pathway, acyloxyla-
tion and following hydrolysis of ester to alcohol pathways, is most
10. Alonso, D. A.; Najera, C.; Pastor, I. M.; Yus, M. Chem. Eur. J. 2010, 16, 5274.