Generation of ArS- and ArSe-Substituted 4-Quinolone Derivatives Using Sodium Iodide As an Inducer

Article abstract of DOI:10.1021/acs.joc.8b01426

An operationally simple sodium iodide-mediated C-S and C-Se bond formation protocol involving substituted 4-quinolone and thiols/diselenide to generate different ArS/ArSe-substituted 4-quinolone derivatives in excellent yields was developed. The versatili

Full text of DOI:10.1021/acs.joc.8b01426

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Article
Generation of ArS and ArSe substituted 4-quinolone
derivatives using sodium iodide as an inducer
Prasanjit Ghosh, Aritra Kumar Nandi, Gautam Chhetri, and Sajal Das
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 27 Sep 2018
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Generation of ArS and ArSe substituted 4-quinolone derivatives using sodium iodide as
an inducer
Prasanjit Ghosh, Aritra Kumar Nandi, Gautam Chhetri and Sajal Das*
Department of Chemistry, University of North Bengal, Darjeeling 734 013, India.
Eꢀmail: sajal.das@hotmail.com; Fax: +91ꢀ353ꢀ2699ꢀ001; Tel: +91ꢀ353ꢀ2776ꢀ381
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O
O
O
Se
R
1
1
1
S
R
Ar
ArSeSeAr
NaI/TBHP
R SH/R SSR
NaI/TBHP
R
1
R2
R2
R2
N
H
N
H
R
N
H
1
00°C, DMSO
100°C, DMSO
R = -H, -Cyclohexyl, -Cyclopropyl,4-OMeC
6 4
H
1
2 examples
14 examples
58-97%
4
-CNC 4, 4-ClC 4, 4-FC
6
H
6
H
6 4
H
4
5-93%
Ar = Ph, 3-MeC
4-ClC 2-CF
R2 = -H, -Cl
6
H
4
, 4-OMeC
6
H
4
R1 = Ph, 2-Naphthyl, -Cyclohexyl
4-MeC ,4-OMeC
4-FC , 4-ClC 4, 2-BrC
R2 = -H
6
H
4
,
3
C
6
H
4,
6
H
4
6 4
H
Avoid of expensive catalyst
NH protection free
Broad substrate scope
6
H
4
6
H
6 4
H ,
Abstract: An operationally simple sodium iodide mediated CꢀS and CꢀSe bond formation protocol involving
substituted 4ꢀquinolone and thiols/diselenide to generate different ArS/ArSe substituted 4ꢀquinolone derivatives
in excellent yields was developed. The versatility of this methodology has been successfully demonstrated by
extension of the suitable reaction conditions to the both substrates having different substituents. This
regioselective CꢀH bond activation approach provides a direct access of structurally diverse 3ꢀ
sulfenylated/selenylated 4ꢀquinolone derivatives. Moreover, this new method proceeds without transition metal
catalyst and preꢀrequisite NHꢀprotection of 4ꢀquinolone derivatives.
Introduction:
Transition metal catalysis brings a new horizon in organic synthesis by introducing a number of unique catalytic
systems. It has huge contribution in almost all classes of organic transformations. For example, the Cꢀhetero
1
atom bond forming reaction is an important milestone in the field of transition metal catalysis. Comparing with
the other Cꢀheteroatom, construction of CꢀS and CꢀSe bonds are relatively new. Formation of CꢀS bond is an
important area of research because many natural products and biologically active molecules are generally
2
comprised of this CꢀS linkage. Diaryl sulfides and a variety of thioethers have incredible applications in
3
4
5
6
treatment of various diseases like Alzheimer’s, Parkinson’s, Breast cancer, HIV infections, etc. The
application of organoselenium compound as synthetic substrates and their useful biological activities have
7
engrossed lots of interest to the synthetic chemists. The toxicological and pharmacological properties of a
compound can easily be tuned by introducing Se, as functional group. On account of hydrogen bond
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acceptor and electron donor properties, organoselenium compounds can dramatically enhance the
8
biological activity of the native substrate. In 1980, Ebselen, an organoselenium compound was firstly
9
discovered which act as promising neuroprotective and antioxidant agent. Some of the diaryl sulfide
and diaryl selenide containing biologically active moieties are shown in Fig. 1. Therefore, many
researchers put their best efforts to develop highly efficient and environmentally benign protocol for the
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construction of CꢀS bond. Recently, an alternative approach for the transitionꢀmetalꢀcatalyzed CꢀS bonds
1
1
formation via CꢀH bond functionalization has been developed which is known as sulfenylation reaction. In
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these reactions arylsulfonyl chlorides, aryl sulfonyl hydrazides, sodium sulfinates, sulfinic acids and
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diaryldisulfides are mostly used as the sulfenylating reagents in the presence of some transition metal catalyst.
Even though these methods are advantageous but certain limitations comprising the use of toxic reagents and
metal catalyst are still persist. Removal of trace amounts of transitionꢀmetal residues from desired bioactive
products is quite challenging, costly and consumption of transition metal also hampers the sustainable
17
development. This inspired the researchers to develop some alternative efficient and practical method for
transition metal free CꢀS/Se bond forming reactions. Metal free approach for the construction of CꢀS and CꢀSe
are rare in literature. In this context, direct use of thiols/diselenide as the sulfenylation/selenation reagent
to generate C–S/CꢀSe bond appears to be the attractive and synthetically desirable.
O
N
NH
O
S
COOH
OH
S
N
N
Se
N
Ebselen
nicotinic acetylcholine receptor
ligand; IC50 = 4.0 nΜ
HIV-1 integrease inhibitor
IC50 = 4.8 ꢀΜ
OH
Se
OMe
N
O
S
OMe
OMe
S
N
S
MeO
N
NO
2
N
NPh
N
Se
N
H
protein tyrosine
phosphatase inhibitor
MCF-7 growth inhibitor
2
O N
IC50 = 13 nΜ
Fig 1: Representative examples of some important biologically active diaryl sulfide and diaryl selenide scaffolds
On the other hand, 4ꢀquinolone represents an important class of potent privileged structures having huge
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application as anticancer, antiꢀHIV, antimalarial, and antidiabetic agent. Our research effort is to
develop the simple protocol for the synthesis of this biologically active scaffold and its selective
functionalization. In this arena, we have previously reported the Carbonylative Sonogashira annulations
2
2
sequence for the synthesis of 4ꢀquinolone, construction of 6ꢀaryl substitutedꢀ4ꢀquinolones via
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regioselective bromination followed by Suzuki crossꢀcoupling reaction, nitro derivatives of 4ꢀquinolones
2
4
via regioꢀcontrolled nitration at ambient condition, ligand free approach for the Cu(II)ꢀmediated CꢀNH
2
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arylation of 4ꢀquinolone derivatives and 3ꢀaroylꢀquinolinꢀ4(1H)ꢀone from 3ꢀiodoꢀquinolinꢀ4(1H)ꢀone
2
6
using Carbonylative Suzuki coupling reaction. There is a single report in the literature, where ꢀSAr
2
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functionality inserted in the 4ꢀquinolone moiety via Pdꢀcatalyzed decarboxylation reaction. Nevertheless,
this protocol consisted of some drawbacks like harsh reaction condition, prolonged reaction time;
essentially requires halogen substituted starting material and most importantly prerequisite protection of ꢀ
NH functional group. Herein, we disclose a simple and efficient metal free route for the direct CꢀS and Cꢀ
Se bond formation of 2ꢀsubstituted/unsubstitutedꢀ4ꢀquinolone scaffolds. It is worth noting that both thiols
and organodiselenide are effectively coupled with 4ꢀquinolone derivatives and furnished the desired product
in good to excellent yields (Fig 2).
Previous Work
R3
O
O
R1
Pd(OAc)
2
(10 mol%)
S
R1
COOH
R3
S
Ag CO (1 equiv)
2
3
S
R2
N
R
+
PPh
3
, DMSO,130°C
R2
N
R
12h
Chem. Asian. J. 2016, 11, 360-366
R3
R = Et, Cyclopropyl
1
= F, R2 = F, Cl
R
Our Contribution
O
O
O
Se
R
1
1
1
S
R
Ar
ArSeSeAr
NaI/TBHP
R SH/R SSR
NaI/TBHP
R
1
R2
R2
R2
N
H
N
H
R
N
100°C, DMSO
100°C, DMSO
H
R = -H, -Cyclohexyl, -Cyclopropyl,4-OMeC
6 4
H
1
2 examples
14 examples
58-97%
4
-CNC 4, 4-ClC 4, 4-FC
6
H
6
H
6 4
H
4
5-93%
R1 = Ph, 2-Naphthyl, -Cyclohexyl
4-MeC ,4-OMeC
4-FC , 4-ClC 4, 2-BrC
R2 = -H
Ar = Ph, 3-MeC
-ClC 2-CF
R2 = -H, -Cl
6 4 6 4
H , 4-OMeC H
4
6
H
4
,
3 6
C H
4,
6
H
4
6 4
H
Avoid of expensive catalyst
NH protection free
Broad substrate scope
6
H
4
6
H
6 4
H ,
Fig 2: Previous protocol for the synthesis of thioether derivatives of 4ꢀquinolone. Metal free approach for
the synthesis of ArS/ArSe substituted product of 4ꢀquinolone is reported herein.
Results and Discussion:
We began our studies with the optimization of CꢀS cross coupling reaction where 2ꢀphenyl 4ꢀquinolone (1a) and
thiophenol were used as model coupling partner. The initial attempts to couple them in the presence of NaI as
an inducer, TBHP as an oxidant in DCE at room temperature was unsuccessful. This was improved when we
switched the solvent. A good yield of the coupled product 2a was observed when DMF was used as solvent. The
yield of the product 2a was further increased to 97% upon performing the reaction in DMSO (Table 1, entry 5)
under the same reaction conditions.
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We next turned our attention to find the optimal reaction temperature by tuning it from rt to 135°C (Table 1,
entries 6ꢀ8). Yield of the coupled product was shrunk upon reducing the reaction temperature, whereas a
comparable yield (94%) was observed when the reaction was carried out at 135°C (Table 1, entry 8). By
2 2
comparison, the identical reaction, in the presence of the other oxidant, H O resulted in only 38% yield of the
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coupled product 2a (Table 1, entry 9). Yield of the product 2a was significantly reduced when the inducer, NaI
was replaced by the other variety of iodide source (Table 1, entries 10ꢀ12). It is noteworthy that the presence of
other inducers and oxidant appear to be redundant in this reaction. On the other hand, when the amount of
inducer and oxidant was reduced in the same reaction under identical condition, resulted in poor yield of the
coupled product 2a (Table 1, entry 13). Additionally, a trace amount of product was observed in the absence of
the oxidant, TBHP (Table 1, entry 14). So it is clear from the optimization table that a combination of NaI (3
equiv.) as inducer and TBHP (3 equiv.) as oxidant in DMSO at 100°C, was found to be optimal for the CꢀS
coupling of 2ꢀphenyl 4ꢀquinolone and thiophenol, leading to excellent yield (97%) of the product 2a after 15 h.
a
Table 1: Screening of the reaction conditions
O
O
SH
S
Inducer
N
solvent, oxidant
temperature
H
N
H
1a
2a
entry
inducer
equiv.)
oxidant
(equiv.)
solvent (ml)
temp (°C)
time (h)
yield (%)
(
1.
2
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
NaI (3)
TBAI (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP (3)
TBHP(3)
TBHP (3)
TBHP (3)
DCE
EtOH
100
100
100
100
100
rt
15
15
15
15
15
15
15
15
15
15
NR
NR
NR
71
3
Toluene
DMF
4
5
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
97
6
Trace
61
7
80
8
135
100
100
94
9
H
2
O
2
(3)
38
10
TBHP (3)
35
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KI (3)
(3)
TBHP (3)
TBHP (3)
TBHP (1)
ꢀ
DMSO
DMSO
DMSO
DMSO
100
100
100
100
15
15
15
15
44
28
I
2
NaI (1)
NaI (3)
29
trace
a
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Reaction condition: 4ꢀquinolone (0.125 mmol, 1 equiv.), thiol (0.1875 mmol, 1.5 equiv.), inducer (1 or 3
equiv.), solvent (2 ml), oxidant (3 equiv.). Isolated yields based on the reactants 1a, the reaction was run for 15
b
h
.
After establishing the optimal reaction conditions for the CꢀS coupling reaction between 2ꢀphenyl 4ꢀquinolone
(1a) and thiophenol, the scope and generality of this protocol was investigated. A variety of 2ꢀsubstituted 4ꢀ
quinolones were treated with a broad range of benzene thiol and the corresponding results are presented in
scheme 1. The coupling reaction proceeded smoothly and resulted in the desired 3ꢀsulfenylated product (2) in
good to excellent yield. A marked influence in the product yield was observed with the substituents present at
the benzene thiol. An electron releasing group substituted benzene thiol resulted in low yield of the
corresponding coupled product compare to electron withdrawing group this might be due the formation of more
stable dimer (see fig. 3). Best yield of the product (2c) was obtained in case of –F substituted benzene thiol as
fluorine is more electron withdrawing group than the other halogens. Bromoꢀsubstituted benzene thiol always
resulted in higher yield of the corresponding products (2e, 2h) than the corresponding chloroꢀderivative (2d, 2j).
This can be explained on the basis of the stability of the intermediate disulphide. Presence of bulky bromo group
at the ortho position, destabilized the dimer and accordingly facilitated the reaction. Yield of the final products
was found to vary with the electronic effects of the group present at Cꢀ2 position of 4ꢀquinolone derivatives.
Comparatively, a higher yield of the coupled product always obtained in the presence of electron releasing
group at Cꢀ2 position of 4ꢀquinolones (2a, 2l and 2i, 2k). Aliphatic thiol smoothly participated in this
sulfenylation reaction and furnished the desired product (2n) in good yield.
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a
Scheme 1: Scope of different substituted 4ꢀquinolone and thiol derivatives for NaI mediated sulfenylation
O
O
R1
S
1
R SH
NaI ( 3 equiv)
N
TBHP (3 equiv), DMSO
100°C, 15 h
H
R
N
H
2
R
1
0
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0
O
S
F
Cl
S
O
Br
O
O
O
O
S
S
S
N
H
N
H
N
H
N
H
N
H
2c, 95%b
2d, 62%b
2e, 97%b
a, 97%b
2b, 58%b
2
Cl
S
O
O
O
O
Br
S
O
S
S
S
N
H
N
H
N
H
N
H
N
H
F
F
F
F
2j, 55%b
2i, 65%b
f, 69%b
2g, 96%b
2h, 90%b
Cl
2
O
O
O
O
S
S
S
S
N
H
N
H
N
H
N
H
Cl
OMe
k, 75%b
2l, 64%b
2m, 65%b
2n, 61%b
2
a
Reaction conditions: 4ꢀquinolone (0.125 mmol, 1 equiv.), thiol (0.1875 mmol, 1.5 equiv.), NaI (0.375 mmol, 3
equiv.), DMSO (2 ml), aqueous TBHP (70 wt% in water, 3 equiv.). Isolated yields based on the reactants 1, the
b
reaction was run for 15 h.
With the successfully establishment of a facile and practical protocol for the sulfenylation reaction, it
was employed to investigate the scope of CꢀSe crossꢀcoupling reaction between 2ꢀsubstituted 4ꢀ
quinolones and diphenyl diselenide for the installation of ꢀSePh group at Cꢀ3 position of 4ꢀquinolone
(
scheme 2). Diphenyl diselenide was efficiently coupled with diverse functionalized 2ꢀsubstituted 4ꢀ
quinolones, resulting in excellent yield of the final coupled product . Notably, the electronic effects of
3
the substituents present at Cꢀ2 position of 4ꢀquinolone have profound impact in the yield of final
coupled products. Alkyl group substituted (cyclopropyl and cyclohexyl) 4ꢀquinolone derivatives reacted
efficiently with diphenyl diselenide and resulted in 88% and 92% yield of the corresponding products
(
entries 3e and 3f) respectively. Whereas, in the presence of electron withdrawing group such as 4ꢀ
chloro and 4ꢀfluoro phenyl substituted 4ꢀquinolone resulted in comparatively low yield of the coupled
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products (entries 3b and 3d). Lowest yield (45%) of the final product (3c) was observed in case of 4ꢀ
cyano phenyl substituted 4ꢀquinolone derivative. 1,2ꢀbis(4ꢀchlorophenyl)diselane were also employed
as coupling partner, afforded the CꢀSe coupled product with good yield (entry 3h). Most reactions of 2ꢀ
phenyl substituted 4ꢀquinolone with various electron releasing group (ꢀOMe and –Me) containing
organodiselenides proceeded well, giving excellent yields of quinolone selenide derivatives (entries 3i
and 3j). Even, sterically crowded orthoꢀtrifluoromethyl group bearing selenide provided the desired
product in 86% yield (entry 3k). Gratifyingly, Cꢀ2 unsubstituted 4ꢀquinolone upon reaction with
diphenyldiselenide furnished the corresponding selenide derivative in good yield (entry 3l).
1
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4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
Scheme 2: Scope of different substituted 4ꢀquinolone derivatives for NaI mediated selenylation
R2
R2
O
Se
O
Se
Se
R1
NaI ( 3 equiv)
R1
R2
N
H
1
TBHP (3 equiv), DMSO
N
H
3
R
100°C, 15 h
R
O
O
O
O
Se
Se
Se
Se
N
H
N
H
N
H
N
H
F
CN
Cl
a, 90%b
3b, 79%b
3c, 45%b
3d, 86%b
3
Cl
O
O
O
Se
Se
O
Se
Se
N
H
Cl
N
H
N
H
N
H
3
e, 88%b
3f, 92%b
3g, 88%b
h, 82%b
3
OMe
O
CF
3
O
O
O
Se
Se
Se
Se
N
H
N
H
N
H
N
H
3
i, 89%b
3j, 93%b
3k, 86%b
3l, 72%b
a
Reaction conditions: 4ꢀquinolone (0.125 mmol, 1 equiv.), organodiselenide (0.1875 mmol, 1.5 equiv.), NaI
0.375 mmol, 3 equiv.), DMSO (2 ml), aqueous TBHP (70 wt% in water, 3 equiv.). Isolated yields based on the
b
(
reactants 1, the reaction was run for 15 h.
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5
5
5
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6
Scheme 3: Studies of reaction mechanism
SH
NaI
S
S
(1)
TBHP, DMSO
97%
(0.25 mmol)
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
PhSSPh (0.1875 mmol), NaI
DMSO, TBHP, 100°C
1
a
2a
(
2)
(
0.125 mmol)
9
3%
PhSSPh (0.1875 mmol), I2
DMSO, TBHP, 100°C
1a
2a
(3)
(0.125 mmol)
55%
TBHP, NaI
TEMPO (1 equiv.), DMSO
1
00°C
2
a
(4a)
(4b)
(4c)
5
0%
TBHP, NaI
SH
TEMPO ( 3 equiv.), DMSO
1
00°C
1a
+
2a
(
0.125 mmol)
TBHP, NaI
N , DMSO
100°C
41%
(
0.1875 mmol)
2
2
a
9
0%
O
I
NaI
1a
(5)
TBHP, DMSO, 100°C
N
H
(0.125 mmol)
4
a
6
5%
4
a
PhSSPh, (0.1875 mmol)
DMSO, TBHP,100°C
2
a
(6)
(
0.125 mmol)
Trace
To gain further insight into the reaction mechanism, a series of control experiments were performed that
are summarized in scheme 3. Under the optimised condition, the benzene thiols were successfully
converted into 1,2ꢀdiphenyl sulfane in 97% yield (scheme 3, eq. 1) which indicated that 1,2ꢀdiphenyl
sulfane might be the important intermediate in the present transformation. Next, we performed the
coupling reaction of 2ꢀphenyl 4ꢀquinolone (1a) with diphenyl disulphide instead of thiophenol under
our established condition and the corresponding desired coupled product was isolated in 93% yield
(scheme 3, eq. 2). This observation, clearly indicated, 1,2ꢀdiphenyl sulfane may be an intermediate in
this transformation. We have also screened the reactivity of iodine instead of NaI in reaction with
PhSSPh and 2ꢀphenyl substituted 4ꢀquinolone and isolated lesser amount (55%) of the desired product
2
a
(scheme 3, eq.
3
). From this observation, it is very much evident that in situ generation of iodine
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from sodium iodide may effectively catalyses the reaction and delivered the excellent yield of the
desired product 2a
To determine, whether this sulfenylation protocol is a radical process, a set of experiments was
performed in the presence of free radical quencher, TEMPO (scheme 3, eq. 4a 4b). Surprisingly, the
.
,
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
yield of the final coupled product 2a decreased to 50% in presence of 1 equiv. of TEMPO. The yield
further decreased to 41% when 3 equiv. of TEMPO was used in the same reaction. Further, the reaction
was performed in inert atmosphere (under N
2
atmosphere), the sulfenylated product 2a was isolated in
9
0% yield, implying the arial oxygen was not the sole oxidant in the present reaction (scheme 3, eq. 4c).
Observations in equation
4, ruling out the possibility of free radical pathway and confirming, 1,2ꢀ
diphenyl sulfane is an essential intermediate in this reaction. Low yield of the product 2a in presence of
TEMPO could be due to incomplete conversion of thiophenol to 1,2ꢀdiphenyl sulfane, as scavenger may
reduce the activity of the oxidant.
Reaction of 2ꢀphenylꢀ4ꢀquinolone and NaI in presence of TBHP, resulted in the corresponding 3ꢀiodo
derivative (4a) in excellent yield (scheme 3, eq.
subjected to the coupling reaction with diphenyl disulphide in absence of NaI, a trace amount of product
2a) was detected. This suggested that iodinated derivative of 4ꢀquinolone was not formed in the
5). Unfortunately, this iodo product (4a) when
(
catalytic cycle (scheme 3, eq. 6).
Non radical Pathway
NaI
ArSH
I
ArSSAr
2
+
TBHP
O
I
I
O
O
ArYYAr
Y = -S,-Se
N
H
R
H
H
Y
Y
R
Ar
Ar
ArY-I
I2
A
N
H
B
R
N
H
B'
HI
O
S
O
HI +
Y
R
Ar
HI
I
2
N
OH
H
OH
2
S
I
Me S + H O
S
I
2
2
D
C
I
Fig 3: Proposed mechanism for the possible reaction
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2
8
Based on the results of controlled experiments (scheme 3) together with the literature reports,
a
proposed mechanism of the CꢀS/Se coupling reaction between 2ꢀsubstituted 4ꢀquinolone with
thiophenol/diphenyl diselenide is shown in Fig 3. Initially, thiols were readily converted into disulfides
under the present reaction conditions. Disulfides/diselenide in presence of I
2
, generated an electrophilic
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
intermediate ArYꢀI (
A
). The intermediate, ArYꢀI quickly reacted with 2ꢀsubstitutedꢀ4ꢀquinolone to form
’
an ionic species B/B , which could be stabilized by the adjacent nitrogen atom. With the loss of proton
in the form of HI, the intermediate,
reacted with DMSO to generate the intermediate
Finally, nucleophilic attack of iodide ion on the iodide atom of
DMS and H O. Proper investigations on the more detailed mechanism are in progress in our laboratory.
Conclusion:
B
furnished the desired couple products. The HI immediately
, which reacted with HI to give intermediate
took place to regenerate I releasing
C
D.
D
2
2
In summary, we have disclosed a method for NaI and TBHP initiated reaction of different 4ꢀquinolone
and thiols/diselenide, providing direct access to various CꢀS/CꢀSe linkage 4ꢀquinolone moieties. Our
protocol is operationally simple and avoids the use of any expensive metal catalyst. Moreover, this
sulfenylation/selenylation methodology is excellent and corresponding products are obtained in good
yields.
Experimental section:
General Considerations:
Unless stated otherwise, all reagents such as various thiols, phenyl diselenide, TBHP, NaI and solvents were
used as received from commercial suppliers. NMR spectra were recorded on 300 MHz spectrometer at 298 K
with calibration done on the basis of solvent residual peak. Products were purified using column
chromatography on silica gel (60ꢀ120 mesh). Ethyl acetate and petroleum ether (60ꢀ80°C) were used as eluents.
Progress of reaction was monitored using silica gel TLC.
Preparation of various thioether and Seleno ether substituted 4-quinolones (2a-2n/3a-3l):
Initially, various 2ꢀ(aryl/alkyl) substituted 4ꢀquinolone (0.125 mmol), thiophenol/diselenide (0.1875 mmol), NaI
(0.375 mmol, 56 mg) and TBHP (3 equiv.) were taken in DMSO (2 ml) in 25 ml round bottomed flask.
Afterwards, the reaction mixture was heated at 100°C for 15 h. Then, it was cooled and diluted with water and
2 4
the product was extracted with ethyl acetate (3 x 20 mL). Organic layer was dried over anhydrous Na SO and
concentrated under reduced pressure. The crude product was then purified using column chromatography.
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Physical characteristics and spectral data of compounds:
2-phenyl-3-(phenylthio)quinolin-4(1H)-one (2a): White solid, Yield = (97%, 39.9 mg), melting point:
1
1
91ꢀ193°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 6.97ꢀ7.05 (m, 3H), 7.14ꢀ7.20 (m, 2H), 7.41 (s, 1H), 7.48ꢀ
1
3
7.54 (m, 5H), 7.71ꢀ7.73 (m, 2H), 8.11 (d, J = 7.8Hz, 1H), 12.29 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
) ẟ
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
1
08.5, 119.2, 124.5, 124.7, 124.8, 125.5, 125.9, 128.5, 129.0, 129.1, 130.2, 132.8, 135.5, 138.8, 139.9,
+
75.5. HRMS (ESIꢀTOF) m/z: [M+H] C21H16NOS calcd for 330.0952; found 330.0972
3-(4-methoxyphenylthio)-2-phenylquinolin-4(1H)-one (2b): White solid, Yield = (58%, 26.0 mg),
1
melting point: 242ꢀ244°C, H NMR (300 MHz, DMSOꢀd ) ẟ 3.67 (s, 3H), 6.78 (dd, J = 6.9Hz, 1.8Hz,
6
2H), 6.98 (dd, J = 6.9Hz, 1.8Hz, 2H), 7.40ꢀ7.43 (m, 1H), 7.51ꢀ7.55 (m, 5H), 7.70ꢀ7.72 (m, 2H), 8.11 (d, J
1
3
=
8.1Hz, 1H), 12.22 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 52.1, 107.0, 111.4, 115.7, 121.1, 121.1,
6
122.4, 124.9, 125.0, 125.7, 125.8, 126.7, 129.3, 132.1, 136.4, 153.0, 154.2, 172.2. HRMS (ESIꢀTOF) m/z:
+
[
M] C H NO S calcd 359.0980; found 359.0984.
2
2
17
2
3-(4-fluorophenylthio)-2-phenylquinolin-4(1H)-one (2c): White solid, Yield = (95%, 41.0 mg), melting
1
point: 240ꢀ242°C; H NMR (300 MHz, DMSOꢀd ) ẟ 7.02ꢀ7.05 (m, 4H), 7.39ꢀ7.44 (m, 1H), 7.50ꢀ7.54 (m,
6
1
3
5
1
1
6
H), 7.71ꢀ7.74 (m, 2H), 8.12 (d, J = 7.5Hz, 1H), 12.28 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 105.8,
05.9, 112.4, 112.7, 115.7, 121.2, 122.4, 124.4, 124.5, 124.7, 125.1, 125.6, 126.7, 129.3, 130.7, 132.0,
+
36.5, 153.4, 155.5, 158.7, 172.0. HRMS (ESIꢀTOF) m/z: [M+H] C21
H
15FNOS calcd 348.0853; found
348.0855.
(4-chlorophenylthio)-2-phenylquinolin-4(1H)-one (2d): White solid, Yield = (62%, 28.2 mg), melting
1
point: 235ꢀ237°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 6.96 (d, J = 1.5Hz, 2H), 6.99 (d, J = 1.8Hz, 2H),
1
3
7.17ꢀ7.20 (m, 1H), 7.38ꢀ7.49 (m, 5H), 7.68ꢀ7.70 (m, 2H), 8.07 (d, J = 7.8Hz, 1H); C NMR (75 MHz
DMSOꢀd
6
) ẟ 107.7, 118.7, 124.1, 124.3, 125.4, 126.8, 128.1, 128.5, 128.8, 129.7, 132.4, 134.9, 137.4,
+
1
39.4, 156.5, 174.9. HRMS (ESIꢀTOF) m/z: [M+H] C21
H
15ClNOS calcd 364.0563; found 364.0568.
3-(2-bromophenylthio)-2-phenylquinolin-4(1H)-one (2e): White solid, Yield = (97%, 49.0 mg), melting
1
point:> 260°C; H NMR (300 MHz, DMSOꢀd ) ẟ 6.86 (dd, J = 8.1Hz, 1.5Hz, 1H), 6.99 (dt, J = 7.5Hz,
6
1
1
1
.5Hz, 1H), 7.18 (dt, J = 7.8Hz, 1.2Hz, 1H), 7.41ꢀ7.54 (m, 7H), 7.74ꢀ7.76 (m, 2H), 8.13 (d, J = 7.8Hz,
13
H), 12.38 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 107.8, 119.3, 119.5, 124.6, 124.8, 125.9, 126.2,
6
26.3, 128.3, 128.6, 128.9, 130.3, 132.8, 132.9, 135.3, 139.5, 140.0, 157.4, 175.3. HRMS (ESIꢀTOF) m/z:
+
[M+H]
21
C H15BrNOS calcd 408.0052; found 408.0053.
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2
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2
2
2
2
2
2
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-(4-methylphenylthio)-2-phenylquinolin-4(1H)-one (2f): White solid, Yield = (69%, 29.6 mg), melting
1
point:185ꢀ187°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 2.20 (s, 3H), 6.95 (d, J = 8.4Hz, 2H), 6.99 (d, J =
13
8
.4Hz, 2H), 7.38ꢀ7.73 (m, 8H), 8.10ꢀ8.16 (m, 1H), 12.25 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
) ẟ 20.9,
1
09.1, 119.2, 124.5, 124.6, 125.9, 128.5, 128.9, 129.1, 129.4, 129.8, 130.1, 130.3, 132.8, 134.1, 135.2,
+
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
135.6, 139.9, 156.8, 175.6. HRMS (ESIꢀTOF) m/z: [M+H] C22
H18NOS calcd 344.1109; found 344.1108.
2
-(4-fluorophenyl)-3-(phenythio)quinolin-4(1H)-one (2g): White solid, Yield = (96%, 41.7 mg), melting
1
point: 230ꢀ232°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 6.99ꢀ7.07 (m, 3H), 7.15ꢀ7.20 (m, 2H), 7.30ꢀ7.44 (m,
13
3H), 7.57ꢀ7.62 (m, 2H), 7.69ꢀ7.77 (m, 2H), 8.12 (d, J = 7.5Hz, 1H), 12.30 (s, 1H); C NMR (75 MHz,
DMSOꢀd
6
) ẟ 108.8, 115.4, 115.6, 119.2, 124.5, 124.7, 124.9, 125.6, 125.9, 129.2, 131.5, 131.6, 131.8,
+
131.9, 132.9, 138.6, 139.9, 156.0, 161.6, 14.9, 175.5. HRMS (ESIꢀTOF) m/z: [M] C21
H14FNOS calcd
3
47.0780; found 347.0782.
3
-(2-bromophenylthio)-2-(4-fluorophenyl)quinolin-4(1H)-one (2h): White solid, Yield = (90%, 47.9
1
mg), melting point: 229ꢀ231°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 6.85 (dd, J = 7.8Hz, 1.5Hz, 1H),
7.00(dt, J = 7.5Hz, 1.5Hz, 1H), 7.15ꢀ7.20 (m, 1H), 7.31ꢀ7.37 (m, 2H), 7.41ꢀ7.61 (m, 4H), 7.73ꢀ7.76 (m,
1
3
2
1
1
4
6
H), 8.13 (dd, J = 7.8Hz, 1.2Hz, 1H), 12.30 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 108.0, 115.5,
15.7, 119.3, 119.5, 124.6, 124.9, 125.9, 126.2, 126.3, 128.4, 131.4, 131.5, 131.6, 131.7, 132.8, 133.0,
+
39.4, 140.0, 156.5, 161.7, 162.8, 165.0, 175.3. HRMS (ESIꢀTOF) m/z: [M+H] C21
H14BrFNOS calcd
25.9958; found 425.9960.
2
-(4-fluorophenyl)-3-(naphthalene-2-ylthio)quinolin-4(1H)-one (2i): White solid, Yield = (65%, 32.3
1
mg), melting point: 170ꢀ172°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.21 (dd, J = 8.4Hz, 2.1Hz, 1H), 7.30ꢀ
13
7
.47 (m, 6H), 7.62ꢀ7.82 (m, 7H), 8.12 (d, J = 7.8Hz, 1H), 12.34 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
) ẟ
1
08.8, 115.4, 115.7, 119.2, 122.9, 124.7, 124.9, 125.4, 125.9, 126.9, 127.1, 127.9, 128.5, 131.2, 131.5,
+
131.6, 131.9, 132.8, 133.9, 136.4, 140.0, 156.1, 161.6, 164.9, 175.6. HRMS (ESIꢀTOF) m/z: [M+H]
C H FNOS calcd 398.1015; found 398.1010.
2
5
17
3
-(4-chlorophenylthio)-2-(4-fluorophenyl)quinolin-4(1H)-one (2j): White solid, Yield = (55%, 26.6
1
mg), melting point : 158ꢀ160°C, H NMR (300 MHz, DMSOꢀd ) ẟ 7.01ꢀ7.04 (m, 2H), 7.22ꢀ7.25 (m, 2H),
6
1
3
7.32ꢀ7.45 (m, 3H), 7.57ꢀ7.62 (m, 2H), 7.69ꢀ7.75 (m, 2H), 8.12 (d, J = 8.1Hz, 1H), 12.35 (s, 1H); C NMR
(
75 MHz, DMSOꢀd ) ẟ 107.9, 114.9, 115.2, 118.8, 124.1, 124.3, 125.4, 126.8, 128.5, 128.9, 130.9, 131.1,
6
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31.2, 131.3, 132.4, 137.3, 139.4, 156.6, 161.1, 164.4, 174.9. HRMS (ESIꢀTOF) m/z: [M+H]
C H ClFNOS calcd 382.0469; found 382.0475.
2
1
14
2
-(4-methoxyphenyl)-3-(naphthalene-2-ylthio)quinolin-4(1H)-one (2k): White solid, Yield = (75%,
1
38.4 mg), melting point:>260°C, H NMR (300 MHz, DMSOꢀd ) ẟ 3.78 (s, 3H), 7.03 (dd, J = 6.6Hz,
6
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2.1Hz, 2H), 7.20 (dd, J = 8.7Hz, 1.8Hz, 1H), 7.37ꢀ7.46 (m, 4H), 7.53 (dd, J = 6.9Hz, 2.1Hz, 2H), ), 7.70ꢀ
1
3
7
.82 (m, 5H), 8.11 (d, J = 7.8Hz, 1H), 12.23 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 55.8, 108.3,
6
1
13.9, 119.2, 122.5, 124.5, 124.6, 124.8, 125.4, 125.9, 126.9, 127.1, 127.7, 128.0, 128.5, 130.7, 131.2,
+
1
32.8, 133.9, 136.8, 140.0, 156.9, 160.9, 175.6. HRMS (ESIꢀTOF) m/z: [M+H] C H NO S calcd
26
20
2
410.1215; found 410.1280.
2
-(4-chlorophenyl)-3-(phenythio)quinolin-4(1H)-one (2l): White solid, Yield = (64%, 29.1 mg), melting
1
point: 243ꢀ245°C, H NMR (300 MHz, DMSOꢀd
6
) ẟ 6.99ꢀ7.07 (m, 3H), 7.16ꢀ7.21 (m, 2H), 7.40ꢀ7.45 (m,
13
1
d
1
3
H), 7.57 (s, 4H), 7.68ꢀ7.77 (m, 2H), 8.12 (d, J = 7.2Hz, 1H), 12.30 (s, 1H); C NMR (75 MHz, DMSOꢀ
6
) ẟ 108.7, 119.2, 124.6, 124.7, 124.9, 125.6, 125.9, 128.6, 129.2, 131.0, 132.9, 134.2, 135.0, 138.5,
+
39.9, 155.8, 175.5. HRMS (ESIꢀTOF) m/z: [M+H] , C H ClNOS calcd 364.0563; found 364.0569.
21 15
-(4-chlorophenylthio)-2-cyclohexylquinolin-4(1H)-one (2m): White solid, Yield = (65%, 28.9 mg),
1
melting point: 238ꢀ240°C; H NMR (300 MHz, DMSOꢀd ) ẟ 1.21ꢀ1.29 (m, 3H), 1.63ꢀ1.98 (m, 7H), 3.69
6
(
t, J = 1.2Hz, 1H), 7.02ꢀ7.13 (m, 4H), 7.35 (t, J = 7.2Hz, 1H), 7.59 (dt, J = 7.2Hz, 1.5Hz, 1H), 7.80ꢀ7.83
13
(m, 1H), 8.05 (dd, J = 8.1Hz, 1.2Hz, 1H), 11.34 (s, 1H); C NMR (75 MHz, DMSOꢀd ) ẟ 25.6, 26.3,
6
30.5, 42.5, 108.8, 116.1, 116.4, 118.9, 124.3, 124.4, 125.8, 128.3, 128.4, 132.6, 134.1, 134.2, 139.9, 162.5,
+
1
75.4. HRMS (ESIꢀTOF) m/z: [M+H] C H ClNOS calcd 370.1032; found 370.1037.
21
21
3
-(cyclohexylthio)-2-phenylquinolin-4(1H)-one (2n): Brownish white solid, Yield = (61%, 25.5 mg),
1
melting point: 236ꢀ238°C; H NMR (300 MHz, DMSOꢀd ) ẟ 0.98ꢀ1.23 (m, 6H), 1.45ꢀ1.51 (m, 3H), 1.66
6
(
d, J = 11.4Hz, 2H), 7.35ꢀ7.40 (m, 1H), 7.49ꢀ7.58 (m, 5H), 7.62ꢀ7.67 (m, 2H), 8.13 (d, J = 7.8Hz, 1H),
1
3
1
1
3
2.01 (s, 1H). C NMR (75 MHz, DMSOꢀd ) ẟ 25.7, 25.9, 33.0, 43.4, 111.6, 118.9, 124.0, 124.1, 125.7,
6
+
28.4, 129.7, 129.8, 132.3, 136.1, 139.7, 154.7, 176.1. HRMS (ESIꢀTOF) m/z: [M+H] C21
36.1422; found 336.1418.
H22NOS calcd
2
-phenyl-3-(phenylselanyl)-quinolin-4(1H)-one (3a): Yellow solid, Yield = (90%, 42.4 mg), melting
1
point:181ꢀ183°C, H NMR (300 MHz, DMSOꢀd ) ẟ 7.09ꢀ7.15 (m, 5H), 7.41ꢀ7.44 (m, 1H), 7.48ꢀ7.51 (m,
6
13
4
H), 7.72 (dd, J = 6.0Hz, 1.5 Hz, 2H), 8.12 (d, J = 7.7Hz, 1H), 12.22 (s, 1H); C NMR (75 MHz, DMSOꢀ
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2
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2
2
2
2
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3
3
3
3
3
3
3
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4
4
4
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5
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5
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d
1
6
) ẟ 108.8, 119.1, 124.0, 124.6, 125.8, 126.1, 128.4, 128.8, 129.1, 129.3, 130.0, 132.7, 134.0, 136.8,
+
40.1, 156.7, 175.4. HRMS (ESIꢀTOF) m/z: [M+H] C21
H16NOSe calcd 378.0397; found 378.0394.
2
-(4-fluorophenyl)-3-(phenylselanyl)-quinolin-4(1H)-one (3b): Yellow solid, Yield = (79%, 39.0 mg),
1
melting point: 230ꢀ232°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.08ꢀ7.14 (m, 5H), 7.32 (t, J = 9.0Hz, 2H),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
7
.38ꢀ7.43 (m, 1H), 7.54ꢀ7.59 (m, 2H), 7.67ꢀ7.72 (m, 2H), 8.12 (d, J = 7.8Hz, 1H), 12.24 (s, 1H); C NMR
(
75 MHz, DMSOꢀd
6
) ẟ 109.0, 115.2, 115.5, 119.1, 124.0, 124.6, 125.8, 126.1, 128.7, 129.4, 131.6, 131.7,
+
1
32.8, 133.2, 133.2, 133.8, 140.0, 155.7, 161.5, 164.8, 175.4. HRMS (ESIꢀTOF) m/z: [M+H]
21
C H
15FNOSe calcd 396.0303; found 396.0307.
4
2
1
-(1,4-dihydro-4-oxo-(3-(phenylselanyl)-quinolin-2-yl)-benzonitrile (3c): Yellow solid, Yield = (45%,
1
2.6 mg), melting point: 171ꢀ173°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.13 (s, 5H), 7.42 (t, J = 6.9Hz,
13
H), 7.65ꢀ7.76 (m, 4H), 7.96 (d, J = 8.1Hz, 2H), 8.13 (d, J = 7.8Hz, 1H), 12.36 (s, 1H); C NMR (75
MHz, DMSOꢀd
6
) ẟ 108.8, 112.6, 118.9, 119.1, 124.1, 124.8, 126.0, 126.1, 128.9, 129.4, 130.3, 132.4,
+
132.9, 133.5, 140.1, 141.0, 155.0, 175.3. HRMS (ESIꢀTOF) m/z: [M+H] C22
15 2
H N OSe calcd 403.0349;
found 403.0340.
2
-(4-chlorophenyl)-3-(phenylselanyl)-quinolin-4(1H)-one (3d): Light yellow solid, Yield = (86%, 44.1
1
mg), melting point: 162ꢀ164°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.08ꢀ7.13 (m, 5H), 7.41 (t, J = 8.1Hz,
1
3
1H), 7.54 (s, 4H), 7.65ꢀ7.73 (m, 2H), 8.12 (d, J = 8.1Hz, 1H), 12.26 (s, 1H), C NMR (75 MHz, DMSOꢀ
d
1
6
) ẟ 109.0, 119.1, 124.1, 124.7, 125.9, 126.1, 128.5, 128.9, 129.4, 131.1, 132.8, 133.7, 134.8, 135.5,
+
40.1, 155.5, 175.3. HRMS (ESIꢀTOF) m/z: [M+H] C21
H15ClNOSe calcd 412.0007; found 411.9988.
2
-cyclopropyl-3-(phenylselanyl)-quinolin-4(1H)-one (3e): White solid, Yield = (88%, 37.4 mg), melting
1
point: 221ꢀ223°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 1.06ꢀ1.22 (m, 4H), 2.74ꢀ2.76 (m, 1H), 7.11ꢀ7.20 (m,
5
1
1
3
H), 7.33 (t, J = 7.5Hz, 1H), 7.65 (t, J = 7.2Hz, 1H), 7.76ꢀ7.79 (m, 1H), 8.04 (d, J = 8.1Hz, 1H), 10.71 (s,
1
3
H); C NMR (75 MHz, DMSOꢀd
6
) ẟ 9.43, 17.3, 110.3, 118.8, 123.9, 124.2, 125.9, 126.0, 128.9, 129.4,
+
32.2, 133.7, 139.8, 155.8, 174.7. HRMS (ESIꢀTOF) m/z: [M+H] C18
H16NOSe calcd 342.0397; found
42.0396.
2
-cyclohexyl-3-(phenylselanyl)-quinolin-4(1H)-one (3f): White solid, Yield = (92%, 43.9 mg), melting
1
point: 238ꢀ240°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 1.24 (d, J = 8.4Hz, 3H), 1.63ꢀ1.80 (m, 7H), 3.70 (s,
1
H), 7.13ꢀ7.20 (m, 5H), 7.35 (t, J = 7.8Hz, 1H), 7.68 (t, J = 8.4Hz, 1H), 7.81 (d, J = 8.1Hz, 1H), 8.05 (d,
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J = 7.8Hz, 1H), 11.25 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
) ẟ 25.6, 26.3, 30.5, 44.9, 109.0, 118.7,
+
1
23.9, 124.2, 126.0, 129.2, 129.5, 132.4, 133.9, 140.1, 162.0, 175.3. HRMS (ESIꢀTOF) m/z: [M+H]
21
C H
22NOSe calcd 384.0867; found 384.0868.
7-chloro-2-phenyl-3-(phenylselanyl)-quinolin-4(1H)-one (3g): Tan powder, Yield = (88%, 45.2 mg),
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
melting point:>270°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.14 (s, 5H), 7.42ꢀ7.51 (m, 6H), 7.72 (s, 1H),
) ẟ 109.5, 118.2, 122.6, 124.9,
1
3
8
1
.11 (d, J = 8.7Hz, 1H), 12.25 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
25.9, 128.5, 128.8, 129.1, 129.4, 130.2, 133.6, 136.6, 137.2, 140.9, 157.1, 174.8. HRMS (ESIꢀTOF) m/z:
+
[
M+H] C21
H
15ClNOSe calcd 412.0007; found 412.0008.
3
-(4-chlorophenylselanyl)-2-phenylquinolin-4(1H)-one (3h): Yellow powder, Yield = (82%, 42.1 mg),
1
melting point: 245ꢀ247°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.17 (q, J = 8.6Hz, 4H), 7.39ꢀ7.43 (m, 1H),
13
7
1
.49 (s, 5H), 7.70ꢀ7.72 (m, 2H), 8.12 (d, J = 7.9Hz, 1H), 12.28 (s, 1H). C NMR (75 MHz, DMSOꢀd
6
) ẟ
08.6, 119.1, 124.1, 124.6, 126.1, 128.5, 129.1, 129.2, 130.1, 130.5, 130.6, 132.7, 132.8, 136.7, 140.1,
+
156.7, 175.2. HRMS (ESIꢀTOF) m/z: [M+H] C21
H15ClNOSe calcd 412.0007; found 412.0011.
3
-(4-methoxyphenylselanyl)-2-phenylquinolin-4(1H)-one (3i): Yellow powder, Yield = (89%, 45.2 mg),
1
6
melting point: 235ꢀ237°C; H NMR (300 MHz, DMSOꢀd ) ẟ 6.74(d, J = 8.7Hz, 2H), 7.10 (q, J = 4.8Hz,
1
3
2
H), 7.38ꢀ7.41 (m, 1H), 7.48ꢀ7.50 (m, 5H), 7.67ꢀ7.70 (m, 2H), 8.11 (d, J = 8.1Hz, 1H), 12.14 (s, 1H). C
NMR (75 MHz, DMSOꢀd
6
) ẟ 55.5, 110.2, 115.1, 119.0, 123.4, 124.0, 124.4, 126.0, 128.4, 129.3, 130.0,
+
1
4
31.8, 132.6, 136.9, 140.0, 156.1, 158.4, 175.4. HRMS (ESIꢀTOF) m/z: [M+H] C22
H18NO
2
Se calcd
03.0503; found 403.0505.
3
-(m-tolyl selanyl)-2-phenylquinolin-4(1H)-one (3j): White powder, Yield = (93%, 45.3 mg), melting
1
point: 228ꢀ230°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 2.51 (s, 3H), 6.91 (s, 2H), 6.96 (s, 1H), 7.00ꢀ7.03 (m,
1
3
1
H), 7.40ꢀ7.43 (m, 1H), 7.49 (s, 5H), 7.70 (s, 2H), 8.13 (d, J = 7.8Hz, 1H), 12.19 (s, 1H). C NMR (75
MHz, DMSOꢀd
6
) ẟ 21.3, 109.3, 119.0, 124.1, 124.4, 126.1,126.4, 126.7, 128.3, 129.0, 129.1, 129.9,
+
1
32.5, 133.7, 136.9, 138.4, 140.1, 156.4, 175.5. HRMS (ESIꢀTOF) m/z: [M+H] C22
H18NOSe calcd
392.0554; found 392.0560.
3
-(2-(trifluoromethyl)phenylselanyl)-2-phenylquinolin-4(1H)-one (3k): White powder, Yield = (86%,
1
4
7.7 mg), melting point: 287ꢀ289°C; H NMR (300 MHz, DMSOꢀd
6
) ẟ 7.21 (d, J = 7.5Hz, 1H), 7.26ꢀ7.39
(
m, 2H), 7.41ꢀ7.49 (m, 6H), 7.61 (d, J = 7.8Hz, 1H), 7.73ꢀ7.75 (m, 2H), 8.12 (d, J = 8.1Hz, 1H), 12.36 (s,
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4
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5
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5
5
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5
5
5
6
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3
1
1
6
H). C NMR (75 MHz, DMSOꢀd ) ẟ 109.0, 120.2, 125.3, 125.7, 126.9, 127.1, 127.9, 128.0, 128.1,
29.4, 130.0, 131.1, 131.5, 133.8, 133.9, 134.8, 137.5, 141.3, 158.4, 176.4. HRMS (ESIꢀTOF) m/z:
+
[
M+H] C22
H
15
F
3
NOSe calcd 446.0271; found 446.0265.
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9
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3-(phenylselanyl)-quinolin-4(1H)-one (3l) : Yellow powder, Yield = (72%, 27.0 mg); H NMR (300
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MHz, DMSOꢀd ) ẟ 7.22ꢀ7.30 (m, 3H), 7.36ꢀ7.41 (m, 3H), 7.59 (d, J = 8.1Hz, 1H), 7.67ꢀ7.72 (m, 1H),
6
1
3
8
.11ꢀ8.18 (m, 2H), 12.16 (s, 1H); C NMR (75 MHz, DMSOꢀd
6
) ẟ 109.9, 118.8, 124.3, 124.7, 125.8,
+
1
26.9, 129.6, 131.2, 131.8, 132.3, 140.1, 143.9, 174.8. HRMS (ESIꢀTOF) m/z: [M+H] C15
H12NOSe
calcd 302.0084; found 302.0077.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
1
13
Copies of the H and C NMR spectra of the products (PDF) are available in the supporting information.
Acknowledgements
We thank the DST, New Delhi for financial support (EMR/2016/001250). PG is thankful to UGC for
his fellowship.
References:
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