Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct 2-Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2-Sulfonylquinolines

Article abstract of DOI:10.1002/ejoc.201601443

A highly efficient iodine/TBHP-mediated one-pot deoxygenative and regioselective 2-sulfonylation of quinoline N-oxides with sodium sulfinate salts has been developed. This metal-, base-, and phosphorus-free protocol employs readily accessible and easy-to-handle reagents and can be conveniently carried out at room temperature under mild conditions, providing an alternative access to a series of 2-sulfonylquinolines and other related heteroaryl sulfone products in moderate-to-excellent yields within a short reaction time.

Full text of DOI:10.1002/ejoc.201601443

A Journal of
Accepted Article
Title: Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct C2-
Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates:
Facile and Regioselective Synthesis of 2-Sulfonyl Quinolines
Authors: Ladawan Sumunnee, Chonchanok Buathongjan, Chaleena
Pimpasri, and Sirilata Yotphan
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601443
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601443
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10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct C2-
Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates:
Facile and Regioselective Synthesis of 2-Sulfonyl Quinolines
Ladawan Sumunnee,[a,b] Chonchanok Buathongjan,[a] Chaleena Pimpasri,[a] and Sirilata Yotphan*[a,b]
Dedication ((optional))
Keywords: Iodine / Quinoline N-Oxide / Sodium Sulfinate / Sulfonylation
Abstract:
A
highly efficient iodine/TBHP-mediated one-pot
good synthetic option. The quinoline sulfone compounds are
known to exhibit antibacterial and antiproliferative activities.[7]
In the last decade, many methods for sulfonylation of
quinolines have been developed. Traditionally, quinoline sulfones
can be synthesized by nucleophilic substitution of heteroaromatic
halides with thiol to form thiolether, followed by oxidation to the
corresponding sulfone (Scheme 1a).[8] Another common method
to construct these sulfones is the transition metal-catalyzed
arylation of sulfinate salts by heteroaromatic halides (Scheme
1b).[9] In 2013, Wu and Cui reported the copper-catalyzed direct
C−H activation and sulfonylation of quinoline N-oxides and
pyridine N-oxides using sulfonyl chlorides as sulfonylating
reagent. However, a harsh phosphorus reagent (PCl3) was
required for further reduction of the N-oxides to the corresponding
sulfonyl quinoline or pyridine products (Scheme 1c).[10] In 2015, Li
developed the synthesis of 2-sulfonyl quinolines from quinoline N-
oxides and sulfonyl chlorides under mild conditions. Nonetheless,
stoichiometric amount of toxic H-phosphonate was necessary for
the successful one-pot sulfonylation and reduction processes
(Scheme 1d).[11] In addition, Han and Pan developed the
synthesis of quinoline sulfone compounds via a copper-catalyzed
deoxygenative C2-sulfonylation of N-oxides with sodium
sulfinates using potassium persulfate (K2S2O8) additive to
promote the C−S bond formation and the N−O bond cleavage in
one-pot transformation (Scheme 1e).[12] Recently, He group and
Xiang group independently reported the synthesis of 2-sulfonyl
quinolines via iodine or iodide-induced C2-sulfonylation of
quinoline N-oxides with sulfonyl hydrazides at 100 °C (Scheme
1f).[13],[14]
deoxygenative and regioselective C2-sulfonylation of quinoline N-
oxides with sodium sulfinate salts has been developed. This metal,
base and phosphorus-free protocol employs readily accessible and
easy to handle reagents, and can be conveniently carried out at room
temperature under mild conditions, providing an alternative access to
a series of C2 sulfonyl quinolines and other related heteroaryl sulfone
products in moderate to excellence yields within a short reaction time.
Introduction
N-heteroaromatic compounds, particularly pyridine and
quinoline derivatives, play important roles in synthesis, catalysis,
material, agricultural, industrial, medicinal and pharmaceutical
chemistry.[1] Pyridine moieties are an essential component in a
number of drugs, pharmaceutical actives, and agrochemical
products. They are also found in a variety of important naturally
occurring compounds such as niacin, pyridoxine, NADP/NADPH
and many alkaloids.[2] While pyridine compounds are employed
widely in various applications, the related quinoline derivatives
have becoming increasingly utilized in agricultural, industrial and
pharmaceutical chemistry.[3] For instant, nalidixic acid is an
effective antibiotic for a treatment against both gram positive and
gram negative bacteria.[4] In addition, quinine,
a naturally
occurring substituted quinoline derivative, has been extensively
used for the treatment of malaria.[5] This quinine compound is
readily detoxified in the body by oxidation process to the 2-
hydroxy derivative leading to a dramatic decrease in therapeutic
activity.[6] Therefore, significant contributions have been focused
on introducing functional groups into the 2-position of quinoline to
prevent the detoxification process. Among these groups, sulfone,
a crucial class of scaffold in natural products, biologically and
pharmaceutically active compounds, has been considered as a
Our group has been interested in developing a metal-free
approach to synthesize biologically active nitrogen-containing
compounds and N-heterocycles.[15] We recently explored the
compatibility of sulfinate salts as a readily available, bench-stable,
non-hygroscopic, easy to handle, and versatile sulfonyl source in
the iodine-catalyzed sulfonylation reaction.[15b],[16] A combination
of iodine and environmentally benign peroxides such as tert-butyl
hydroperoxide (TBHP) or hydrogen peroxide (H2O2) under mild
operating conditions can lead to broadening of the reaction scope,
[a]
[b]
Center of Excellence for Innovation in Chemistry (PERCH-CIC),
Department of Chemistry, Faculty of Science, Mahidol University,
Rama VI Road, Bangkok 10400, Thailand.
Center of Catalysis, Department of Chemistry, Faculty of Science,
Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
E-mail: sirilata.yot@mahidol.ac.th
along with
a better functional group tolerance. With our
continuous efforts toward the development of a metal-free
synthetic option, herein, we wish to report a facile regioselective
synthesis of C2-sulfonyl quinolines and other related N-
heterocycles via I2/ TBHP-mediated one-pot deoxygenation and
direct sulfonylation of quinoline N-oxide substrates using sodium
sulfinates as a stable, odourless and easy to handle sulfonyl
http://chemistry.sc.mahidol.ac.th/en/people/faculty/sirilata-yotphan/
Supporting information for this article is given via a link at the end of
the document
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10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
source (Scheme 1g). Our present method is metal, base, and
phosphorus-free, features a simple experimental procedure, can
be conveniently conducted at room temperature under mild
conditions (which is in a sharp contrast to He’s and Xiang’s
sulfonylation methods using sulfonyl hydrazide substrates) with a
one-pot reaction was essentially complete after 2 hours (entry
8).[18] Other polar and non-polar solvents are less effective
(entries 1 ̶ 7). Employing H2O2 as the oxidant gave slightly lower
yield of product (70%, entry 9). However, other oxidants including
di-tert-butyl hydroperoxide (DTBP; entry 10) led to a significant
decrease in yield or no reactions. The combinations of TBHP with
other forms of anionic iodide and cationic iodine such as NaI,
tetrabutylammonium iodide (TBAI) and N-iodosuccinimide (NIS)
broad scope of substrates, and offers
a useful synthetic
alternative to access a number of C2-sulfonyl quinolines and other
heteroaryl sulfone products in reasonable to excellent yields
showed much lower activity (entries 11 ̶ 13). The reaction
temperature for this transformation was carefully optimized;
however, lower yield of product was found as temperature
increases (entries 14 ̶
15).[17] Additionally, no reaction was
observed in the absence of I2 (entry 16), and only 20% yield of
product 3a was obtained when the oxidant was omitted from the
reaction (entry 17). These results highlight the importance of both
I2 and TBHP in this transformation.
Table 1. Optimization of reaction conditions.[a]
Entry
Reagent
Oxidant
Solvent
Temp
[°C]
Yield[b]
[%]
1
2
I2
I2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
H2O2
CH3CN
CH2Cl2
toluene
THF
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
100
r.t.
r.t.
53
28
3
I2
23
4
I2
61
5
I2
CH3OH
H2O
46
6
I2
41
7
I2
DMSO
DMF
71
8
I2
85 (82[c]
)
9
I2
DMF
70
within a short reaction time.
10
11
12
13
14
15
16
17
I2
DTBP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
-
DMF
5
NaI
TBAI
NIS
I2
DMF
17
DMF
11
Scheme 1. Synthetic Approaches for C2-Sulfonyl Quinolines.
DMF
49
DMF
70
I2
DMF
56
Results and Discussion
-
DMF
0
I2
DMF
20
To evaluate the feasibility of using sulfinate salts as sulfonyl
precursors in
a
metal-free one-pot deoxygenative and
[a] Conditions: 1a (0.5 mmol, 1 equiv.), 2a (1.25 mmol, 2.5 equiv.), reagent
(0.55 mmol, 1.1 equiv.), oxidant (1.5 mmol, 3.0 equiv.), solvent (2 mL), 2 h.
[b] GC yield. [c] Isolated yield after purification by SiO2 chromatography.
regioselective sulfonylation of heteroaromatic N-oxide substrates,
we initiated the studies by examining a reaction between quinoline
N-oxide (1a) and sodium p-toluene sulfinate (2a) under various
conditions and selected results are summarized in Table 1.[17]
When a reaction of N-oxide 1a and sodium sulfinate salt 2a was
carried out in the presence of I2 (1.1 equiv.) in combination with
aqueous tert-butyl hydroperoxide (aq. TBHP; 3 equiv.) using
CH3CN as a solvent at room temperature, the C2-sulfonyl
quinoline 3a could be obtained in a promising 53% yield (Table 1,
entry 1). Screening of solvents revealed that DMF is the optimal
solvent, in which the desired sulfone product 3a can be
accomplished in very high quantity (82% isolated yield) and the
Overall, the optimal conditions for I2/TBHP-induced
deoxygenation and direct C2-sulfonylation of quinoline N-oxide
and sodium sulfinate 1a was established (Table 1, entry 8; 1 equiv.
of quinoline N-oxide, 2.5 equiv. of sodium sulfinate,1.1 equiv. of
I2, 3 equiv. of aq. TBHP, DMF, r.t., 2 h). With these conditions in
hand, we sought to expand the substrate scope that is applicable
for this transformation. Therefore, the one-pot deoxygenation and
sulfonylation reaction between quinoline N-oxide (1a) and variety
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10.1002/ejoc.201601443
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of sodium sulfinate salts (2) were evaluated and the results are
listed in Table 2. Various types of arylsulfinate sodium salts are
well-compatible with standard conditions, affording the desired 2-
sulfonyl quinoline products (3a–3m) in moderate to excellent
quantities. As anticipated, sodium phenylsulfinate reacted with
N-oxides were also examined under the optimal conditions. As
illustrated in Table 3, both p-toluenesulfinate sodium salt and
methanesulfinate sodium salt showed a tolerance toward a range
of substituted quinoline N-oxide substrates, and the one-pot
deoxygenation and sulfonylation can be achieved without any
quinoline N-oxide smoothly, furnishing the product 3b in 78% yield. difficulties, allowing a facile preparation of 2-sulfonyl quinolines in
Arylsulfinate with halogen-substituents (Cl, Br, and I) could serve
as practical substrates for the I2/TBHP-mediated deoxygenation
and sulfonylation reactions and the products 3c–3e were
achieved in moderate to high quantities (53–76%).
Benzenesulfinate substrates bearing electron-donating (methoxy
group) or electron–withdrawing (nitro and cyano groups)
moderate to excellent yields. The presence of alkyl group (methyl
or isopropyl) at C3 or C8 position of quinoline N-oxide does not
appear to sterically interfere with the transformation and the
sulfone products 4a1
̶ 4c2 can be collected in in reasonable to
decent amounts. Remarkably, the reactions of sodium sulfinates
with quinoline N-oxide substrate bearing strong electron donating
substituents also delivered products 3f–3h in good yields. Notably, group (-OCH3) proceeded efficiently at room temperature and
arylsulfinates bearing substitutents at ortho position (o-CH3 and
o-Br) could be converted into their corresponding 2-sulfonyl
gave the corresponding products in good to excellent yields (4d1
and 4d2; 95% and 74%, respectively). On the other hand, only a
quinoline products 3i and 3j in synthetically useful yields; however, trace amount of product was found in case of quinoline N-oxide
in the case of steric bulky mesitylene sulfinate salt, a modest
amount of product 3k (42%) was obtained. Moreover,
substrate bearing a strong electron-withdrawing substituent (-
NO2). These outcomes indicated that electronic variations from
substituents on N-oxide have a remarkable influence on the
efficiency of the reaction.
heteroarylsulfinates
such
as
pyridinylsulfinate
and
thiophenylsulfinate sodium salts are viable substrates for this one-
pot transformation resulting in a formation of quinoline sulfone
products 3l and 3m in 50% and 25%, respectively. Apart from
arylsulfinate salts, we examined a reaction of alkyl sulfinate
sodium salt. To our delight, sodium methanesulfinate underwent
smooth one-pot reaction with quinoline N-oxide (1a) affording
product 3n in high yield (79%). Conversely, sodium triflinate,
which has very strong inductive effect from trifluoromethane
group, was not an effective substrate, suggesting that the nature
of the sodium sulfinate could have an impact on a product
formation.
Table 3. Substrate scope of quinoline and other hereoaromatic N-oxides.[a]
Table 2. Reaction of quinoline N-oxide 1a with various sodium sulfinate
salts.[a]
[a] Conditions: 1 (1.0 mmol, 1.0 equiv.), 2 (2.5 mmol, 2.5 equiv.), I2 (1.1
mmol, 1.1 equiv.), aq. TBHP (3.0 mmol, 3.0 equiv.), DMF (4 mL). r.t., 2 h;
isolated yields after purification by SiO2 chromatography.
We also explored the one-pot deoxygenation and
sulfonylation on other related heteroaromatic N-oxide substrates.
Substituted pyridine N-oxides such as 4-phenylpyridine and 4-
chloropyridine N-oxides can be converted to the monosubstituted
[a] Conditions: 1a (1.0 mmol, 1.0 equiv.), 2 (2.5 mmol, 2.5 equiv.), I2 (1.1
mmol, 1.1 equiv.), aq. TBHP (3.0 mmol, 3.0 equiv.), DMF (4 mL), r.t., 2 h;
isolated yields after purification by SiO2 chromatography.
sulfonyl pyridine products (Table 3, 4f1 ̶ 4g2) with slightly low or
moderate yields under the optimal conditions. Additionally,
isoquinoline N-oxide can react with sodium sulfinate and
The reactions between sodium sulfinate salts and various
quinoline N-oxides, pyridine N-oxides, and other heteroaromatic
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10.1002/ejoc.201601443
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sulfonylation took place at C3 position as a major product (e.g. 4h
and 4i), which is the opposite regioisomer that could be obtained
from He and Xiang’s iodine/iodide-induced sulfonylation of N-
oxides using sulfonyl hydrazides.[13],[14] Unfortunately, other N-
oxides including pyrimidine, pyrazine and quinoxazaline N-oxide
substrates are unable to convert to their target products under the
established conditions.
To provide further evidence on the role of iodine and TBHP,
the reaction was carried out without the oxidant. The yield of
product 3a was significantly reduced (19%) when subjecting 1.1
equivalence of I2 to this reaction (Scheme 3e), which emphasized
the necessity of I2/TBHP combination in this one-pot
transformation. We also speculated that the electrophilic iodine
species could be involve in this non-radical process; therefore,
NaIO generated in situ from I2 and NaOH was used, and the
reaction gave the quinoline sulfone product in 37% and 60%
yields in the absense and presence of TBHP, respectively. These
results suggest that I2 is probably converted to an electrophilic
iodine intermediate such as NaIO or NaIO2 prior to reacting with
substrates under standard conditions.
It is noteworthy that the synthesis of 2-sulfonyl quinolines
(3a, 3b and 3n) via the developed iodine/TBHP-mediated
deoxygenation and direct sulfonylation of N-oxides could be
safely conducted on a gram scale (10 mmol) with a similar efficacy
to small scale reactions (Scheme 2). This could prove the
practicality and suggest a potential application in the industry of
this synthetic approach.
Scheme 2. Gram scale-reactions.
To gain insight into the reaction mechanism, a series of
control experiments were carried out (Scheme 3). When a radical
inhibitor was employed in the reaction of quinoline N-oxide 1a and
p-toluenesulfinate sodium salt 2a, no inhibition was observed
under the optimal conditions (Scheme 3a). The quinoline sulfone
product can be obtained in 67%, 79%, and 80% in the presence
of TEMPO, BHT, and hydroquinone, respectively, suggesting that
the reaction possibly involves a non-radical pathway. In addition,
no formation of the desired product 3a was observed under
established conditions when replacing quinoline N-oxide
substrate (1a) with 2-iodoquinoline N-oxide or 2-iodoquinoline or
quinoline (Scheme 3b). These results implied that either 2-
iodoquinoline N-oxide or 2-iodoquinoline or quinoline might not be
the intermediate generated from iodination process in this
reaction. We also questioned that p-toluenesulfonyl iodide (TsI)
could be the intermediate in this transformation because a
reaction between sodium sulfinate and molecular iodine can
generate
a
relatively unstable sulfonyl iodide.[19] Thus, p-
toluenesulfonyl iodide (TsI) was prepared and utilized in the
subsequent experiment.[20] However, treating the quinoline N-
oxide 1a with TsI in the presence and absence of TBHP oxidant
resulted in a significant reduction of the product yield (13%) or no
reaction (Scheme 3c). Therefore, the sulfonyl iodide is unlikely to
be the reactive intermediate that could be converted to the sulfone
product in this transformation.[21] Furthermore, sodium p-
toluenesulfinate was replaced by sodium p-toluenesulfonate in
this reaction (Scheme 3d). Nevertheless, no desired product was
obtained, which implies that p-toluenesulfinate does not turn into
p-toluenesulfonate under oxidative conditions, and the sulfinate
salt rather than the sulfonate undergoes direct sulfonylation with
the N-oxide in this transformation.
Scheme 3. Control experiments.
Based on the above results and relevant literature,[11],[13], [22],
a plausible mechanism for this metal-free-inducted one-pot
[23]
deoxygenation and sulfonylation is proposed in Scheme 4. Under
the optimal reaction conditions, the initial process could
presumably involves
a reaction of I2 and TBHP to form
electrophilic iodine species (“ I+ ”) such as hypoiodite (IO-) or iodite
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10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
-
(IO2 ) via an in situ iodination.[24] Then, nucleophilic attack of this
neat method, and only partial data are listed. Melting points were
determined on Buchi Melting Point M-565 apparatus. High resolution mass
spectroscopy (HRMS) data were analysed by a high-resolution micrOTOF
instrument with electrospray ionization (ESI). The structures of known
compounds were corroborated by comparing their 1H NMR, 13C NMR data
with those of literature.
“ I+ ” species by the N-oxide will generate intermediate A. This
intermediate further reacts with sodium sulfinate salt leading to a
formation of intermediate B. Subsequent elimination would result
in an N ̶ O bond cleavage and furnish the corresponding quinoline
sulfone product in regioselective fashion.
General Procedure for the Synthesis of Compounds of Compounds
3a ̶ 3n and 4a1 ̶ 4i: A 20 ml oven-dried scintillation vial equipped with a
magnetic stir bar was charged with a mixture of heteroaryl N-oxide
substrate (1.00 mmol, 1.00 equiv.), sodium sulfinate salt (2.50 mmol, 2.50
equiv.), iodine (I2) (1.10 mmol, 1.10 equiv.), N,N-dimethylformamide (DMF)
(4.00 mL) and TBHP in water (3.00 mmol, 3.00 equiv.). The vial was
capped and the reaction mixture was stirred at room temperature for 2
hours. Upon completion, saturated Na2S2O3 (5 mL) and distilled deionized
H2O (12 mL) was added, and the mixture was extracted with ethyl acetate
(EtOAc) (2 × 25 mL). The combined organic layer was washed with
saturated NaCl, dried over anhydrous Na2SO4, and concentrated in vacuo.
The crude product was purified by SiO2 column chromatography to afford
a desired 2-sulfonyl heteroarene product.
1
2-tosylquinoline (3a)[11]: White solid (231 mg, 82% yield). H NMR (400
MHz, CDCl3): δ = 8.32 (d, J = 8.4 Hz, 1H), 8.14 (t, J = 8.4 Hz, 2H), 7.98 (d,
J = 8.4 Hz, 2H), 7.82 (d, J = 8.0 Hz, 1H), 7.73 (dt, J = 8.0, 1.2 Hz, 1H),
7.62–7.58 (m, 1H), 7.28 (d, J = 8.0 Hz, 2H), 2.35 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 158.2, 147.3, 144.7, 138.6, 136.0, 130.8, 130.2,
129.7, 129.0, 128.9, 128.7, 127.6, 117.6, 21.5 ppm. HRMS (ESI): calcd for
C16H13NO2SNa [M+Na]+ 306.0559; found 306.0560.
Scheme 4. Proposed reaction mechanism.
2-(phenylsulfonyl)quinoline (3b)[11]: White solid (209 mg, 78% yield). 1H
NMR (400 MHz, CDCl3): δ = 8.33 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.4 Hz,
1H), 8.13–8.09 (m, 3H), 7.82 (d, J = 8.4 Hz, 1H), 7.75–7.70 (m, 1H), 7.62–
7.46 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.9, 147.3, 139.0,
138.7, 133.6, 130.9, 130.2, 129.1, 128.9, 128.8, 128.7, 127.6, 117.6 ppm.
HRMS (ESI): calcd for C15H11NO2SNa [M+Na]+ 292.0403; found 292.0412.
Conclusions
The I2/TBHP-mediated one-pot deoxygenation and direct
C2-sulfonylation of quinoline N-oxides using sodium sulfinate as
a sulfonyl precursor has been developed for the regioselective
synthesis of 2-sulfonyl quinolines. The present method is metal,
base and phosphorus-free, utilizes inexpensive and readily
available reagents, features a simple experimental procedure,
demonstrates good functional group compatibility, proves to be
versatile for a range of sodium sulfinate salts and many quinoline
N-oxide substrates, and can be efficiently conducted on a gram
scale. This one-pot protocol provides a convenient synthetic
alternative to access a series of C2-sulfonyl quinolines and other
related compounds at room temperature with moderate to
excellent yields of products in a short reaction time. Further
mechanistic study and expansion of the synthetic utility of this
methodology are currently under investigation.
2-((4-chlorophenyl)sulfonyl)quinoline (3c)[11]: Yellow solid (229 mg,
76% yield). 1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.4 Hz, 1H), 8.17
(d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 8.07–8.03 (m, 2H), 7.85 (d, J
= 8.4 Hz, 1H), 7.78–7.74 (m, 1H), 7.65–7.61 (m, 1H), 7.47 (td, J = 8.4, 2.0
Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.7, 147.3, 140.5, 138.8,
137.4, 131.1, 130.5, 130.2, 129.3, 129.2, 128.8, 127.7, 117.4 ppm. HRMS
(ESI): calcd for C15H10ClNO2SNa [M+Na]+ 326.0013; found 326.0020.
2-((4-bromophenyl)sulfonyl)quinoline (3d) [12]: Off-white solid (242 mg,
70% yield). 1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.4 Hz, 1H), 8.17
(d, J = 8.4 Hz, 1H), 8.11 (d, J =8.4 Hz, 1H), 7.99–7.96 (m, 2H), 7.85 (d, J
= 8.0 Hz, 1H), 7.78–7.74 (m, 1H), 7.65–7.62 (m, 3H) ppm. 13C NMR (100
MHz, CDCl3): δ = 157.6, 147.4, 138.8, 137.9, 132.3, 131.1, 130.5, 130.2,
129.3, 129.1, 128.8, 127.7, 117.4 ppm. HRMS (ESI): calcd for
C15H10BrNO2SNa [M+Na]+ 369.9513; found 369.9524.
Experimental Section
2-((4-iodophenyl)sulfonyl)quinoline (3e) [12]: White solid (208 mg, 53%
yield). 1H NMR (400 MHz, CDCl3): δ = 8.37 (d, J = 8.8 Hz, 1H), 8.17 (d, J
= 8.8 Hz, 1H), 8.12 (d, J = 8.8 Hz, 1H), 7.88–7.75 (m, 6H), 7.65 (dt, J =
8.0, 1.2 Hz, 1H) ppm.13C NMR (100 MHz, CDCl3): δ 157.7, 147.4, 138.8,
138.6, 138.3, 131.1, 130.4, 130.3, 129.3, 128.8, 127.7, 117.5, 101.9 ppm.
HRMS (ESI): calcd for C15H10INO2SNa [M+Na]+ 417.9369; found 417.9370.
General Information: Unless otherwise noted, all reagents were obtained
from commercial suppliers and used without further purification. Column
chromatography was performed over silica gel (SiO2; 60 Å silica gel, Merck
Grade, 70–230 Mesh). GC experiments were carried out with a GC-FID on
chromatograph equipped with ZB-1 dimethyl polysiloxane column (30.0 m
× 0.25 mm ID × 0.25 µm). 1H and 13C NMR spectra were recorded on
Bruker-AV400 spectrometers in CDCl3 solution, at 400 and 100 MHz,
respectively. NMR chemical shifts are reported in ppm, and were
measured relative to CHCl3 (7.24 ppm for 1H and 77.00 ppm for 13C). IR
spectra were recorded on Bruker FT-IR Spectrometer Model ALPHA by
2-((4-methoxyphenyl)sulfonyl)quinoline (3f)[12]: White solid (215 mg,
72% yield). 1H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 8.4 Hz, 1H), 8.16–
8.12 (m, 2H), 8.06– 8.02 (m, 2H), 7.83 (d, J = 8.0 Hz, 1H), 7.76–7.72 (m,
1H), 7.63–7.59 (m, 1H), 6.98–6.94 (m, 2H), 3.80 (s, 3H) ppm.13C NMR
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10.1002/ejoc.201601443
European Journal of Organic Chemistry
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(100 MHz, CDCl3): δ = 163.8, 158.5, 147.3, 138.6, 131.2, 130.8, 130.4,
130.3, 128.9, 128.6, 127.6, 117.4, 114.3, 55.5 ppm. HRMS (ESI): calcd
for C16H13NO3SNa [M+Na]+ 322.0514; found 322.0526.
2-(thiophen-2-ylsulfonyl)quinoline (3m)[11] : Yellow solid (69 mg, 25%
yield); 1H NMR (400 MHz, CDCl3): δ = 8.37 (d, J = 8.4 Hz, 1H), 8.18 (d, J
= 8.4 Hz, 2H), 7.89–7.86 (m, 2H), 7.80–7.76 (m, 1H), 7.70 (dd, J = 4.8, 1.2
Hz, 1H), 7.67–7.63 (m, 1H), 7.12–7.09 (m, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 157.9, 147.3, 139.7, 138.8, 135.3, 135.2, 131.1, 130.3, 129.2,
128.9, 127.8, 127.7, 117.3 ppm. HRMS (ESI): calcd for C13H10NO2S2
[M+H]+ 276.0147; found 276.0152.
2-((4-nitrophenyl)sulfonyl)quinoline (3g): Light yellow solid (195 mg,
62% yield). m.p. 143.0 – 145.0 °C. 1H NMR (400 MHz, CDCl3): δ = 8.41 (d,
J = 8.8 Hz, 1H), 8.36–8.30 (m, 4H), 8.22 (d, J = 8.8 Hz, 1H), 8.09 (d, J =
8.8 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.76 (d, J =
7.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ = 156.8, 150.7, 147.3,
144.6, 139.1, 131.3, 130.5, 130.1, 129.6, 128.9, 127.7, 124.0, 117.4 ppm.
IR: ν˜ = 3015, 1521, 1380, 1345, 1212, 1178, 966, 768, 549 cm-1. HRMS
(ESI): calcd for C15H10N2O4SNa [M+Na]+ 337.0259, found 337.0253.
2-(methylsulfonyl)quinoline (3n) [12]: Yellow solid (163 mg, 79% yield),
1H NMR (400 MHz, CDCl3): δ = 8.39 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.4
Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.90–7.87 (m, 1H), 7.82–7.78 (m, 1H),
7.68–7.64 (m, 1H), 3.34 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =
157.4, 146.8, 138.8, 131.1, 129.9, 129.1, 129.0, 127.8, 116.0, 39.7 ppm.
HRMS (ESI): calcd for C10H9NO2SNa [M+Na]+ 230.0252; found 230.0263.
4-(quinolin-2-ylsulfonyl)benzonitrile (3h): White solid (199 mg, 68%
yield). m.p. 192.6 – 194.8 °C. 1H NMR (400 MHz, CDCl3): δ = 8.40 (d, J =
8.4 Hz, 1H), 8.25–8.21 (m, 3H), 8.09 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.0
Hz, 1H), 7.82–7.76 (m, 3H), 7.68–7.64 (m, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 156.9, 147.3, 143.1, 139.0, 132.6, 131.3, 130.1, 129.7, 129.6,
128.9, 127.7, 117.4, 117.3, 117.1 ppm. IR: ν˜ = 3091, 2922, 2235, 1558,
1497, 1319, 1168, 1130, 1074, 833, 683, 651, 558 cm-1; HRMS (ESI):
calcd for C16H10N2O2SNa [M+Na]+ 317.0374; found 317.0361.
3-methyl-2-tosylquinoline (4a1)[14]: Yellow solid (262 mg, 88% yield). 1H
NMR (400 MHz, CDCl3): δ = 8.01 (s, 1H), 7.92–7.87 (m, 3H), 7.71 (d, J =
8.0 Hz, 1H), 7.60 (dt, J = 8.4, 1.2 Hz, 1H), 7.56–7.52 (m, 1H), 7.32 (d, J =
8.0 Hz, 2H), 2.82 (s, 3H), 2.42 (s, 3H) ppm.13C NMR (100 MHz, CDCl3): δ
= 156.9, 144.6, 144.4, 139.7, 135.7, 129.8, 129.6, 129.3, 129.2, 129.0,
128.8, 128.4, 126.5, 21.5, 18.7 ppm. HRMS (ESI): calcd for
C17H15NO2SNa [M+Na]+ 320.0721; found 320.0729.
2-(o-tolylsulfonyl)quinoline (3i): Off-white solid (209 mg, 74% yield).
m.p. 192.6 – 194.8 °C. 1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.8 Hz,
1H), 8.29 (dd, J = 8.0, 1.2 Hz, 1H), 8.15 (d, J = 8.8 Hz, 1H), 8.08 (d, J =
8.4 Hz, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.77–7.72 (m, 1H), 7.65–7.61 (m,
1H),7.49–7.45 (m, 1H), 7.41–7.38 (m, 1H), 7.24–7.21 (m, 1H), 2.53 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.1, 147.1, 139.1, 138.6, 137.1,
133.9, 132.4, 130.9, 130.6, 130.3, 129.1, 128.8, 127.7, 126.4, 117.7, 20.7
ppm. IR ν˜ = 3057, 2965, 1577, 1472, 1309, 1163, 1094, 751, 708, 639
cm-1. HRMS (ESI): calcd for C16H13NO2SNa [M+Na]+ 306.0565; found
306.0568.
3-methyl-2-(methylsulfonyl)quinoline (4a2): White solid (172 mg, 78%
yield). m.p. 118.2 – 120.1 °C. 1H NMR (400 MHz, CDCl3): δ 8.06–8.01 (m,
2H), 7.79–7.76 (m, 1H), 7.73–7.69 (m, 1H), 7.63–7.59 (m, 1H), 3.52 (s,
3H), 2.82 (d, J = 0.8 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.8,
144.2, 139.7, 129.9, 129.5, 129.2, 128.9, 127.6, 126.9, 39.9, 17.7 ppm. IR
ν˜ = 3013, 2931, 1561, 1292, 1128, 960, 788, 766, 599, 508 cm-1. HRMS
(ESI): calcd for C11H12NO2S [M+H]+ 222.0583; found 222.0591.
8-methyl-2-tosylquinoline (4b1) [14]: White solid (247 mg, 83% yield); 1H
NMR (400 MHz, CDCl3): δ = 8.30 (d, J = 8.4 Hz, 1H), 8.17 (d, J = 8.4 Hz,
1H), 8.03 (dd, J = 6.8, 1.2 Hz, 2H), 7.65 (d, J = 8.0 Hz, 1H), 7.56 (d, J =
6.8 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 2.66 (s, 3H),
2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.3, 146.3, 144.6,
138.7, 138.3, 135.9, 130.8, 129.4, 129.3, 128.8, 128.7, 125.5, 116.7, 21.6,
17.5 ppm. HRMS (ESI): calcd for C17H15NO2SNa [M+Na]+ 320.0721;
found 320.0734.
2-((2-bromophenyl)sulfonyl)quinoline (3j): Yellow solid (232 mg, 67%
yield). m.p. 162.3 – 164.7 °C. 1H NMR (400 MHz, CDCl3): δ = 8.51 (d, J =
8.0 Hz, 1H), 8.40 (d, J = 8.8 Hz, 1H), 8.31 (dd, J = 8.8, 2.0 Hz, 1H), 7.99
(d, J = 8.4 Hz, 1H); 7.88 (d, J = 8.4 Hz, 1H), 7.74–7.69 (m, 1H), 7.65–7.56
(m, 3H), 7.44 (dt, J = 8.0, 1.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 157.1, 147.1, 138.3, 135.0, 134.8, 132.5, 130.9, 130.2, 129.2, 128.9,
127.8, 127.7, 121.3, 118.6 ppm. IR ν˜ = 3054, 1572, 1425, 1317, 1171,
1140, 1023, 827, 735, 569 cm-1. HRMS (ESI): calcd for C15H10BrNO2SNa
[M+Na]+ 369.9508; found 369.9517.
8-methyl-2-(methylsulfonyl)quinoline (4b2): Colorless oil (159 mg, 72%
yield). 1H NMR (400 MHz, CDCl3): δ = 8.38 (d, J = 8.4 Hz, 1H), 8.07 (d, J
= 8.4 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.59–7.55
(m, 1H), 3.40 (s, 3H), 2.79 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ =
156.5, 148.4, 145.9, 139.1, 138.1, 131.2, 129.0, 125.7, 115.5, 39.4, 17.6
ppm. IR ν˜ = 3016, 2929, 1573, 1494, 1304, 1162, 1114, 960, 762 cm-1.
HRMS (ESI): calcd for C11H12NO2S [M+H]+ 222.0583; found 222.0592.
2-(mesitylsulfonyl)quinoline (3k)[14]: Off-white solid (130 mg, 42% yield).
1H NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.4
Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.76–7.71 (m,
1H), 7.64–7.60 (m, 1H), 6.93 (s, 2H), 2.66 (s, 6H), 2.27 (s, 3H) ppm.13
C
NMR (100 MHz, CDCl3): δ = 159.5, 147.1, 143.5, 141.1, 138.3, 132.8,
132.4, 131.9, 130.7, 130.4, 128.8, 127.6, 116.8, 23.0, 21.0 ppm. IR ν˜ =
2925, 1602, 1498, 1305, 1162, 1129, 755, 685, 659 cm-1. HRMS (ESI):
calcd for C18H17NO2SNa [M+Na]+ 334.0878; found 334.0898.
8-isopropyl-2-tosylquinoline (4c1): Yellow oil (246 mg, 76% yield). 1H
NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 8.8 Hz, 1H), 8.17 (d, J = 8.8 Hz,
1H), 8.02 (d, J = 8.0 Hz, 2H), 7.66 (dd, J = 8.0, 2.0 Hz, 1H), 7.61–7.53 (m,
2H), 7.31 (d, J = 8.0 Hz, 2H), 4.03 (sep, J = 6.8 Hz, 1H), 2.38 (s, 3H), 1.22
(d, J = 6.8 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3): δ = 157.2, 148.1,
145.1, 144.5, 138.8, 135.8, 129.4, 129.3, 129.0, 128.8, 126.6, 125.3, 116.4,
27.9, 23.0, 21.5 ppm. IR ν˜ = 3064, 2962, 2869, 1596, 1491, 1373, 1320,
1166, 1077, 813, 704 cm-1. HRMS (ESI): calcd for C19H19NO2SNa [M+Na]+
348.1034; found 348.1047.
2-(pyridin-3-ylsulfonyl)quinoline (3l): White solid (134 mg, 50% yield).
m.p. 118.2 – 120.1 °C. 1H NMR (400 MHz, CDCl3): δ = 9.31–9.30 (m, 1H),
8.80 (dd, J = 4.8, 1.2 Hz, 1H), 8.43 – 8.39 (m, 2H), 8.21 (d, J = 8.4 Hz, 1H),
8.10 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.80–7.75 (m, 1H), 7.67–
7.63 (m, 1H), 7.49–7.45 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 157.4,
154.0, 149.9, 147.4, 139.0, 136.8, 135.5, 131.2, 130.2, 129.5, 128.9, 127.7,
123.6, 117.2 ppm. IR ν˜ = 3098, 3076, 1575, 1418, 1318, 1169, 1087, 764,
650, 573 cm-1. HRMS (ESI): calcd for C14H10N2O2SNa [M+Na]+ 293.0355;
found 293.0362.
8-isopropyl-2-(methylsulfonyl)quinoline (4c2): Yellow oil (99 mg, 40%
yield).1H NMR (400 MHz, CDCl3): δ = 8.39 (d, J = 8.4 Hz, 1H), 8.05 (d, J =
8.4 Hz, 1H), 7.74–7.69 (m, 2H), 7.63 (t, J = 7.6 Hz, 1H), 4.22 (sep, J = 6.8
Hz, 1H), 3.39 (s, 3H), 1.37 (d, J = 6.8 Hz, 6H) ppm.13C NMR (100 MHz,
CDCl3): δ = 156.3, 147.9, 144.6, 139.3, 129.3, 129.2, 127.0, 125.6, 115.2,
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10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
39.3, 27.8, 23.2 ppm. IR ν˜ = 3060, 2952, 2874, 1589, 1495, 1370, 1301,
1160, 1068, 810, 714 cm-1. HRMS (ESI): calcd for C13H15NO2SNa [M+Na]+
272.0721; found 272.0732.
6-bromo-3-tosylisoquinoline (4i): Orange-brown solid (119 mg, 33%
yield). m.p. 204.1 – 205.5 °C. 1H NMR (400 MHz, CDCl3): δ = 9.58 (d, J =
0.4 Hz, 1H), 9.08 (s, 1H), 8.43 (dd, J = 8.8, 0.4 Hz, 1H), 7.82 (d, J = 8.0
Hz, 2H), 7.27–7.22 (m, 4H), 2.34 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 155.3, 144.6, 144.0, 142.0, 138.1, 130.6, 129.9, 128.1, 127.5, 125.9,
123.8, 123.5, 102.7, 21.5 ppm. IR ν˜ = 3387, 3014, 2980, 1681, 1544,
1350, 1260, 1139, 945, 513 cm-1. HRMS (ESI): calcd C16H12BrNO2SNa
[M+Na]+ 383.9664; found 383.9673.
6-methoxy-2-tosylquinoline (4d1) [12]: White solid (297 mg, 95% yield).
1H NMR (400 MHz, CDCl3): δ = 8.17 (d, J = 8.4 Hz, 1H), 8.09 (d, J = 8.8
Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.96 (d, J = 8.4 Hz, 2H), 7.36 (dd, J =
9.2, 2.8 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 2.8 Hz, 1H), 3.89 (s,
3H), 2.35 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.7, 155.6, 144.5,
143.5, 136.7, 136.4, 131.7, 130.3, 129.6, 128.8, 124.1, 118.1, 104.5, 55.7,
21.6 ppm. HRMS (ESI): calcd for C17H15NO3SNa [M+Na]+ 336.0665; found
336.0670.
Acknowledgements
The authors gratefully acknowledge financial support from
Thailand Research Fund (TRF) Grant RSA5980008, Faculty of
Science, Mahidol University, the Office of the Higher Education
Commission and Mahidol University under the National Research
Universities Initiative and the Center of Excellence for Innovation
in Chemistry (PERCH-CIC). The authors also thank Department
of Chemistry and the Central Instrument Facility (CIF) at Faculty
of Science, Mahidol University for providing research facilities.
6-methoxy-2-(methylsulfonyl)quinoline (4d2): Off-white solid (176 mg,
74% yield). m.p. 112.1 – 114.3 °C. 1H NMR (400 MHz, CDCl3): δ = 8.24 (d,
J = 8.8 Hz, 1H), 8.03 (t, J = 8.4 Hz, 2H), 7.44 (dd, J = 9.2, 2.8 Hz, 1H), 7.11
(d, J = 2.8 Hz, 1H), 3.94 (s, 3H), 3.31 (s, 3H) ppm.13C NMR (100 MHz,
CDCl3): δ = 159.8, 154.8, 143.1, 136.9, 131.4, 130.7, 124.5, 116.7, 104.7,
55.7, 40.0 ppm. IR ν˜ = 2921, 1620, 1497, 1386, 1307, 1159, 1121, 764,
458 cm-1. HRMS (ESI): calcd for C11H12NO3S [M+H]+ 238.0532; found
238.0537.
4-phenyl-2-tosylpyridine (4f1): White solid (75 mg,24% yield). m.p. 149.5
– 151.4 °C. 1H NMR (400 MHz, CDCl3): δ 8.66 (d, J = 4.8 Hz, 1H), 8.38 (d,
J = 1.2 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.65 (dd, J = 8.0, 2.0 Hz, 2H),
7.61 (dd, J = 4.8, 2.0 Hz, 1H), 7.52–7.47 (m, 3H), 7.31 (d, J = 8.0 Hz, 2H),
2.39 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.6, 150.8, 144.8,
136.4, 135.9, 130.0, 129.8, 129.4, 128.9, 127.1, 124.3, 119.8, 21.6 ppm.
IR ν˜ = 3064, 3031, 1589, 1457, 1318, 1299, 1161, 759, 666, 584 cm-1.
HRMS (ESI): calcd for C18H16NO2S [M+H]+ 310.0896; found 310.0903.
Keywords: Iodine • Quinoline N-Oxide • Sodium Sulfinate •
Sulfonylation
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2-(methylsulfonyl)-4-phenylpyridine (4f2): White solid (63 mg, 27%
yield). m.p. 107.4–109.8 °C. 1H NMR (400 MHz, CDCl3): δ = 8.74 (dd, J =
6.8, 4.0 Hz, 1H), 8.29 (d, J = 1.2 Hz, 1H), 7.73 (dd, J = 5.2, 1.6 Hz, 1H),
7.66 (dd, J = 8.0, 1.6 Hz, 2H), 7.53–7.47 (m, 3H), 3.25 (s, 3H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 158.7, 151.1, 150.5, 136.3, 130.2, 129.4,
127.1, 124.9, 118.8, 40.1 ppm. IR ν˜ = 3035, 2932, 1591, 1466, 1294,
1129, 1094, 951, 767, 759, 539 cm-1. HRMS (ESI): calcd for
C12H11NO2SNa [M+Na]+ 256.0408; found 256.0421.
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4-chloro-2-tosylpyridine (4g1)[11]: White solid (102 mg, 38% yield). 1H
NMR (400 MHz, CDCl3): δ = 8.52 (d, J = 5.2 Hz, 1H), 8.15 (d, J = 2.0 Hz,
1H), 7.90 (d, J = 8.0 Hz, 2H), 7.41 (dd, J = 5.2, 2.0 Hz, 1H), 7.31 (d, J =
8.0 Hz, 2H), 2.39 (s, 3H) ppm.13C NMR (100 MHz, CDCl3): δ = 160.2, 151.1,
146.2, 145.2, 135.1, 129.8, 129.0, 126.9, 122.4, 21.6 ppm. HRMS (ESI):
calcd for C12H11ClNO2S [M+H]+ 268.0194; found 268.0203.
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4-chloro-2-(methylsulfonyl)pyridine (4g2): White solid (77 mg, 40%
yield). m.p. 82.8 – 84.2 °C.1H NMR (400 MHz, CDCl3): δ = 8.60 (d, J = 5.2
Hz, 1H), 8.06 (dd, J = 2.0, 0.4 Hz, 1H), 7.53 (dd, J = 5.2, 2.0 Hz, 1H), 3.21
(s, 3H) ppm.13C NMR (100 MHz, CDCl3): δ = 159.2, 150.9, 146.6, 127.7,
121.7, 39.9 ppm. IR ν˜ = 3082, 3027, 1564, 1454, 1294, 1170, 1135, 963,
744, 536 cm-1. HRMS (ESI): calcd for C6H6ClNO2SNa [M+Na]+ 213.9700;
found 213.9706.
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3-tosylisoquinoline (4h); White solid (85 mg, 30% yield). m.p. 175.1 –
176.9 °C. 1H NMR (400 MHz, CDCl3): δ = 9.19 (s, 1H), 8.61 (s, 1H), 7.97
(d, J = 8.4 Hz, 4H), 7.82–7.78 (m, 1H), 7.76–771 (m, 1H), 7.28 (d, J = 8.4
Hz, 2H), 2.35 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.6, 152.3,
144.5, 136.3, 135.2, 131.8, 130.1, 129.6, 129.3, 128.7, 128.1, 127.7, 120.8,
21.5 ppm. IR ν˜ = 3390, 3025, 2985, 1684, 1570, 1378, 1270, 1165, 966,
800, 485 cm-1. HRMS (ESI): calcd C16H13NO2SNa [M+Na]+ 306.0559;
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601443
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Ladawan Sumunnee, Chonchanok
Buathongjan, Chaleena Pimpasri,
Sirilata Yotphan*
Page No. – Page No.
Iodine/TBHP-Promoted One-Pot
Deoxygenation and Direct C2-
Sulfonylation of Quinoline N-Oxides
with Sodium Sulfinates: Facile and
Regioselective Synthesis of 2-
Sulfonyl Quinolines
A facile synthesis of 2-sulfonyl quinolines from quinoline N-oxides and sodium
sulfinates, employing the combination of I2/TBHP in one-pot deoxygenation and
direct sulfonylation is described. This reaction proceeds at room temperature under
mild conditions, and provides products in moderate to excellent yields.
Subject: Metal-Free Sulfonylation Reaction
This article is protected by copyright. All rights reserved.