Catalyst-Controlled Selectivity in the Synthesis of C2- and C3-Sulfonate Esters from Quinoline N-Oxides and Aryl Sulfonyl Chlorides

Article abstract of DOI:10.1002/cctc.201600555

The first example of the catalyst-controlled selective synthesis of C2- and C3-sulfonate-ester-substituted quinolines was developed by employing LaCl₃ and chitosan@CuI catalysts, respectively. This protocol provides an expeditious route to an important class of quinoline derivatives frequently found in many biologically active compounds and features good practicality, high efficiency, and environmental friendliness. In addition, the easily recoverable chitosan@copper catalysts can be recycled five times without significant loss of catalytic performance.

Full text of DOI:10.1002/cctc.201600555

DOI: 10.1002/cctc.201600555
Communications
Catalyst-Controlled Selectivity in the Synthesis of C2- and
C3-Sulfonate Esters from Quinoline N-Oxides and Aryl
Sulfonyl Chlorides
Beibei Ying,[a] Jun Xu,[a] Xiaolei Zhu,[a] Chao Shen,*[b] and Pengfei Zhang*[a]
The first example of the catalyst-controlled selective synthesis
of C2- and C3-sulfonate-ester-substituted quinolines was devel-
oped by employing LaCl3 and chitosan@CuI catalysts, respec-
tively. This protocol provides an expeditious route to an impor-
tant class of quinoline derivatives frequently found in many
biologically active compounds and features good practicality,
high efficiency, and environmental friendliness. In addition, the
easily recoverable chitosan@copper catalysts can be recycled
five times without significant loss of catalytic performance.
obtain novel functionalized quinolines having a sulfonate ester
moiety.
In recent years, supported catalysts have received tremen-
dous attention, because they can be reused many times. Vari-
ous catalyst supports have been prepared, such as chitosan,[6]
zeolites,[7] silica,[8] magnetic materials,[9] and polymers.[10]
Herein, on the basis of our previous work on chitosan-
supported catalysts,[6a] we report a novel, efficient, and highly
practical procedure for the catalyst-controlled selective synthe-
sis of C2- and C3-sulfonate-ester-substituted quinolines from
quinoline N-oxides and aryl sulfonyl chlorides.[11] Most impor-
tantly, the chitosan (CS)@CuI catalyst can be recycled.
Functionalized quinolines are common motifs in organic
chemistry,[1] biological chemistry,[2] and material sciences.[3]
Among them, the synthesis of quinoline derivatives that con-
tain sulfonic esters has draw significant attention from re-
searchers (Figure 1).[4] Traditionally, most of these compounds
are prepared by the reactions of phenols with sulfonic acids or
with thiols by using the H2O2/POCl3 system or under micro-
wave-assisted methods and catalyzed by copper oxide. Howev-
er, many of these methods suffer from harsh reaction condi-
tions, substrate pretreatment, and multistep reactions.[5]
Hence, it is necessary to develop a green, efficient strategy to
To optimize the reaction conditions, we commenced our
study by conducting the reaction of quinoline N-oxide with
p-tolylsulfonyl chloride as the model reaction, and the results
are shown in Table 1. Upon performing the reaction in the
presence of CuBr2 (20 mol%) and K2CO3 (2.0 equiv.) at 1008C in
1,2-dichloroethane (DCE), C3-substituted product 3a, C2-sub-
stituted product 4a, and 1c were obtained in yields of 19, 27,
and 15%, respectively (Table 1, entry 1). The structures of prod-
ucts 3d and 4a were confirmed by X-ray crystallographic anal-
ysis (Figures 2 and 3). On the basis of the preliminary inquiry,
Figure 1. Examples illustrating the importance of sulfonate esters.
Figure 2. ORTEP view of 3d.
we screened various metal catalysts, such as zinc trifluorome-
thylsulfonate [Zn(OTf)2], CuI, PdCl2, CeCl3, SmCl3, LaCl3 (Table 1,
entries 2–4; also see the Supporting Information). Moreover,
some chitosan-supported copper catalysts, including
CS@CuSO4, CS@Cu(OAc)2, and CS@CuI, were tested (Table 1,
entries 11–13). To our delight, upon using LaCl3 as the catalyst,
target product 3a was obtained in 47% yield (Table 1, entry 4),
and CS@CuI was the best catalyst to obtain target product 4a
(Table 1, entry 13). Other additives, such as Cs2CO3, KOH, and
AcOH, were tested to increase the yield of 3a (Table 1,
[a] B. Ying, J. Xu, X. Zhu, Prof. P. Zhang
College of Materials, Chemistry and Chemical Engineering
Hangzhou Normal University
Hangzhou 310036 (China)
E-mail: chxyzpf@hotmail.com
[b] Dr. C. Shen
College of Biology and Environmental Engineering
Zhejiang Shuren University
Hangzhou (China)
Supporting Information for this article can be found under http://
dx.doi.org/10.1002/cctc.201600555.
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was detected without any base (Table 1, entry 15).
Pleasingly, K2CO3 dramatically improved the yield of
4a, and this showed that the base was the key spe-
cies in this transformation. Finally, the influence of
solvents was studied, and relative to that obtained
with other solvents (e.g., DMF, 1,4-dioxane, toluene,
and DMSO), DCE gave the best result (Table 1,
entry 19; also see the Supporting Information).
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
Base
Solvent
Yield [%][b]
(3a/4a/1c)
1
2
3
4
CuBr2
CeCl3
SmCl3
LaCl3
K2CO3
K2CO3
K2CO3
K2CO3
–
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DMF
1,4-dioxane
DCE
DCE
DCE
DCE
DCE
DCE
DCE
19/27/15
With the optimized reaction conditions in hand,
we further investigated the scope of the synthesis of
sulfonate esters at the C3 position of the quinoline
ring by using various sulfonyl chlorides, and the re-
sults are summarized in Table 2. Notably, the reac-
tions were slightly sensitive to the electronic proper-
ties of the sulfonyl chlorides. The target products
were obtained in moderate yields only upon using
sulfonyl chlorides with electron-withdrawing groups
or containing heterocycles. Regrettably, C4- and C6-
substituted quinoline N-oxides could not afford the
CÀO coupling products.
25/29/9
20/15/19
47/trace/trace
N.R.
32/10/trace
27/32/trace
N.R.
5
LaCl3
6
7
LaCl3
LaCl3
Cs2CO3
KOH
8
9
LaCl3
LaCl3
LaCl3
AcOH
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
–
NaOAc
Na2CO3
Cs2CO3
K2CO3
K2CO3
N.R
N.R
10
11
12
13
14
15
16
17
18
19
20[c]
CS@CuSO4
CS@Cu(OAc)2
CS@CuI
–
CS@CuI
CS@CuI
CS@CuI
CS@CuI
CS@CuI
CS@CuI
trace/32/13
trace/28/18
trace/88/trace
trace/26/59
N.R.
trace/16/17
15/61/8
15/25/21
24/43/10
trace/88/trace
Subsequently, we further investigated the scope of
the synthesis of C2-substituted sulfonate esters, and
the results are summarized in Table 3. To our surprise,
various sulfonate esters were obtained in moderate
to excellent yields. Generally, the reaction efficiency
was slightly sensitive to the electronic properties of
the sulfonyl chlorides, and substrates with electron-
donating groups showed better reactivity. This result
may be attributed to the fact that the electron-with-
DCE
toluene
DCE
[a] Reaction conditions: 1a (0.2 mmol), 2a (2.0 equiv.), base (2.0 equiv.), catalyst
(20 mol%), solvent (2.0 mL), 1008C, air, 12 h. Ts=MeC6H4SO2. [b] Yield of isolated
product; N.R.=no reaction. [c] Performed under a N2 atmosphere
drawing groups do not favor the conversion of the quinoline
N-oxides into the corresponding aryloxy anions. To our delight,
heterocyclic sulfonyl chlorides were also successfully trans-
formed into the corresponding target products. Next, quinoline
N-oxide derivatives with methyl groups at the 4-, 6-, and 7-po-
sitions afforded the corresponding products in moderate yields
under the optimized reaction conditions. C4-substituted prod-
uct 4s was obtained by employing isoquinoline N-oxide as the
substrate (Scheme 1).
Recovery and recycling of the catalyst is a major concern for
the sustainability of transition-metal-catalyzed reactions, be-
cause transition-metal catalysts are usually costly and toxic. As
CS@CuI is not soluble in most organic solvents, upon comple-
tion of the reaction it can be separated by simple filtration.
The recyclability of the catalyst was thus studied, and the re-
sults are shown in Figure 4. The catalyst maintained its high
catalytic activity after five runs of the reaction.
On the basis of our reaction results and literature reports,[12]
Figure 3. ORTEP view of 4a.
a
plausible mechanism was proposed (Scheme 2). First,
entries 6–8); however, K2CO3 was still the best. With-
out K2CO3, product 3a could not been obtained
(Table 1, entry 5), and DCE was the most effective sol-
vent (Table 1, entries 9 and 10). Amazingly, 4a could
be obtained in 26% yield without a catalyst (Table 1,
entry 14). Subsequently, some bases were screened
by using CS@CuI as the catalyst (Table 1, entries 16–
18; also see the Supporting Information). No product Scheme 1. CS@CuI-catalyzed synthesis of sulfonate esters of isoquinoline N-oxides.
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product 4a is obtained by the combined action of
p-tolylsulfonyl chloride and K2CO3.
Table 2. Scope of sulfonate esters at the C3 position of the quinoline.[a]
In conclusion, we presented a novel reaction with
efficient regioselectivity and easy operation by using
quinoline N-oxides and sulfuryl chlorides as sub-
strates. In particular, the efficient and easily recovera-
ble chitosan@copper catalyst in this catalytic system
was recycled five times without a huge loss in
catalytic performance. Further mechanistic studies on
this transformation are currently ongoing in our
laboratory.
Experimental Section
Syntheses
3: A mixture of quinoline N-oxide 1 (0.2 mmol), arene
sulfonyl chloride 2 (2.0 equiv.), LaCl3 (9.8 mg, 20 mol%),
and K2CO3 (55.2 mg, 2.0 equiv.) in DCE (2.0 mL) in
a 25 mL Schlenk tube was stirred at 1008C for 12 h. After
cooling to room temperature, the mixture was filtered
through a pad of Celite. The solvent was removed under
reduced pressure and the residue was then purified by
column chromatography (200–300 mesh silica gel, petro-
leum ether/EtOAc=20:1).
4: A mixture of quinoline N-oxide 1 (0.2 mmol), arene
sulfonyl chloride
2
(2.0 equiv.), CS@CuI (45.8 mg,
[a] Reaction conditions: 1 (0.2 mmol), 2 (2.0 equiv.), K2CO3 (2.0 equiv.), LaCl3 (20 mol%),
solvent (2.0 mL), 1008C, air, 12 h. Yield of isolated products are given.
20 mol%), and K2CO3 (55.2 mg, 2.0 equiv.) in DCE
(2.0 mL) in a 25 mL Schlenk tube was stirred at 1008C for
12 h. After cooling to room temperature, the mixture
was filtered through a pad of Celite. The solvent was re-
moved under reduced pressure and the residue was
then purified by column chromatography (200–
300 mesh silica gel, petroleum ether/EtOAc=20:1).
1c: A mixture of quinoline N-oxide 1 (0.2 mmol), arene sulfonyl
chloride 2a (2.0 equiv.), and K2CO3 (55.2 mg, 2.0 equiv.) in DCE
(2.0 mL) in a 25 mL Schlenk tube was stirred at 1008C for 0.5 h.
After cooling to room temperature, the mixture was filtered
through a pad of Celite. The solvent was removed under reduced
pressure. The gathered residue was then purified by column chro-
matography (200–300 mesh silica gel, petroleum ether/EtOAc=
5:1).
Figure 4. Catalyst recycling for the reaction.
quinoline N-oxide and the sulfuryl chloride are acti-
vated through coordination with LaCl3 to give 1a’,
which results in the loss of a ÀOTs ion.[12a] Then, the
ÀOTs anion attacks intermediate 1a“,[12b] and target
product 3a is obtained through nucleophilic substi-
tution of ÀOTs and dissociation of the LaCl3 complex
in the presence of K2CO3. On the other hand, rear-
rangement of 1a into 1c can occur through the as-
sistance of p-tolylsulfonyl chloride.[12c–e] The existence
of intermediate 1c has been confirmed by 1H NMR
and 13C NMR spectroscopy, as shown in the Support-
ing Information. Subsequently, the CS@CuI catalyst
coordinates with intermediate 1c. In the end, target Scheme 2. Plausible reaction mechanism.
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Table 3. Scope of sulfonate esters at the C2 position of the quinoline.[a]
[a] Reaction conditions: 1 (0.2 mmol), 2 (2.0 equiv.), K2CO3 (2.0 equiv.), CS@CuI (20 mol%), solvent (2.0 mL), 1008C, air, 12 h. Yields of isolated products are
given.
Catalyst recycling experiment
Keywords: copper
· heterogeneous catalysis · sulfur ·
To probe whether CS@CuI was recyclable, the C2-sulfonate-ester
reaction was repeated five times with the same catalyst sample,
which was recovered after each reaction. The initial amount of cat-
alyst was 45.8 mg (20 mol%). Reactions were performed for 12 h.
Upon completion of the reaction, the catalyst was filtered off,
washed twice with ethyl acetate and water, and then dried for 3 h
at 608C. It was then stored under ambient conditions overnight
and used again.
supported catalysts · sustainable chemistry
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Received: May 8, 2016
Revised: June 6, 2016
Published online on && &&, 0000
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B. Ying, J. Xu, X. Zhu, C. Shen,* P. Zhang*
&& – &&
Catalyst-Controlled Selectivity in the
Synthesis of C2- and C3-Sulfonate
Esters from Quinoline N-Oxides and
Aryl Sulfonyl Chlorides
S-uper selective: The catalyst-
practicality, high efficiency, and environ-
mental friendliness. In addition, the
easily recoverable CS@copper catalyst
can be recycled five times without sig-
nificant loss of catalytic performance.
controlled selective synthesis of C2- and
C3-sulfonate-ester-substituted quino-
lines is developed, employing LaCl3 and
chitosan@CuI (CS@CuI) as catalysts,
respectively. This protocol features good
&
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www.chemcatchem.org
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!