Iron(iii)-catalyzed chelation assisted remote C-H bond oxygenation of 8-amidoquinolines

Article abstract of DOI:10.1039/c7ob02159c

Iron catalyzed site selective and chelation assisted C-H functionalization in 8-amidoquinolines is achieved. The remote C5-benzoxylation with benzoyl peroxide produced a variety of potentially bioactive 8-arylcarboxamido-5-benzoyloxy quinoline derivatives. The efficiency of the reaction reflects from the wide substrate scope with electronic differentiation on carboxamide and acyl peroxide in addition to tolerance of halo-substitutions on either of the aryls. The reaction is additive, silver free and proceeds without the exclusion of air or moisture.

Full text of DOI:10.1039/c7ob02159c

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Iron (III)-catalyzed chelation assisted remote C-H bond
oxygenation of 8-amidoquinolines.
Received 00th January 20xx,
Accepted 00th January 20xx
Botla Vinayak, Pilli NavyaSree and Malapaka Chandrasekharam*
DOI: 10.1039/x0xx00000x
Iron catalyzed site selective and chelation assisted C-H functionalization in 8-amidoquinolines is achieved. The remote C5-
benzoxylation with benzoyl peroxide produced a variety of potentially bioactive 8-arylcarboxamido-5-benzoyloxy quinoline
derivatives. The efficiency of the reaction reflects from the wide substrate scope with electronic differentiation on
carboxamide and acyl peroxide in addition to tolerance of halo substitutions on either of the aryls. The reaction is additive,
www.rsc.org/
silver
free
and
proceeds
without
the
exclusion
of
air
or
moisture.
on 8-amidoquinolines are still in nascent stage. Copper catalyst
is known to activate remote C5-H bonds for the transformation
to the corresponding C-X (X= C, O, S, P, N, Cl, Br) bonds.4f, 7c, 8
Introduction
Direct C-O bond formation reactions employ transition-metal-
catalyzed C–H functionalization as the most powerful tool.1
Due to the high electronegativity of the oxygen element and
the strong metal–oxygen bond strength, C-H cleavage for the
construction of C-O bond remained relatively under
developed.2 CAr-H Benzoxylation is gaining importance due to
the potential applications of the benzoxylated products i.e.,
the use of aryl carboxylates as alternative electrophilic
partners in palladium free cross-couplings and also as latent
phenols.3 Substituted quinolines, often obtained from 5-
Hydroxyquinoline derivatives, have been widely investigated in
the area of reversing multidrug resistance and are known to
show good biological activity and hence in the recent their
synthesis attracted much attention.4 Some of the reported
methods for the synthesis of 5-hydroxyquinoline include the
Bucherer reaction of 5-aminoquinoline, the Skraup reaction of
3,5-dichloroaniline, and the deprotection of triflates or tert-
butyl carbonate esters. The enzyme mediated transformation
of arene oxides to the corresponding hydroxyquinoline
employed microsamal epoxide hydrolase.5 In view of the
limitations associated with these methods, development of a
highly efficient procedure for the synthesis of 5-
hydroxyquinoline derivatives is highly warranted.
Though
C5-allylation8a
and
–benzylation8b
of
8-
amidoquinolines could be effected by Iron, known to be a
cheap metal for noble task,9 the reactions employ
operationally difficult inert conditions and energy intensive
drastic reaction conditions. Further ortho-benzoxylation8k and
remote C5-acetoxylation4f of 8-amidoquinolines under copper
catalysis are recently reported which require base or additives
(Scheme 1). To our knowledge iron catalyzed oxygenation of
geometrically inaccessible C5-H in 8-amidoquinolines that is
located far from the coordinative metal center is unexplored.
Scheme 1. C5-benzoxylation of 8-Amidoquinolines.
Further, substituted 8-amino quinoline urea derivatives are
important building blocks for the formation of organic helical
structures through dynamic covalent chemistry.6 While
chelation assisted directing group strategy for selective ortho
C-H activation of benzamides attracted extensive
investigations,7 geometrically inaccessible C-H bond activations
In continuation of our efforts towards copper and iron
catalyzed C-H functionalizations,10 (C-C,
C
-O, C-N) and
particularly
CAr-oxygenations,10c
we
attempted the
oxygenation of 8-amidoquinoline with acylperoxide and FeCl3.
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We are delighted to observe that the benzoxylation occured at were investigated.11 Finally portion wise addition of BP, and
remote C-5 position of the quinoline moiety (Scheme 1). stirring a solution of 1a and iron(III) chloride for 24 h in open
We further investigated this reaction and herein report for the air at 90 °C were found to be optimum reaction conditions.
first time, the iron catalyzed C5 oxygenation of 8-
amidoquinoline derivatives and the corresponding urea
Scheme 2. Substrate scope of C5-benzoxylation.a
derivative.
Results and discussion
We began our study with 4-methyl-N-(quinolin-8-yl)benzamide
OCOPh
OCOPh
OCOPh
OCOPh
OCOPh
OCOPh
OCOPh
(
1a) as a model substrate. Stirring a solution of (1a), iron(III)
O
O
O
O
N
N
N
N
chloride and benzoyl peroxide (BP) in a toluene solution at
room temperature resulted in the recovery of starting
material. On
H
H
H
H
N
N
N
N
O
2a 63%
O
2b 70%
O
2c 61%
2d 65%
OCOPh
O
O
N
N
N
H
N
H
Table 1. Optimization of the reaction conditions.a
H
H
N
N
N
N
F
F
O
F
2e 73%
O
2g 57%
O
2f 61%
O
2h 58%
O
OCOPh
OCOPh
OCOPh
OCOPh
OCOPh
OCOPh
O
Cl
Cl
N
H
N
H
N
N
H
H
N
N
N
N
Cl
Cl
OCOPh
Cl
2m 58%
2i 60%
O
Cl
2j 60%
Cl 2k 60%
OCOPh
O
O
N
O
Entry
Catalyst
Temp
(°C)
RT
yield [%]b
N
H
N
N
H
H
N
H
N
N
N
Br
Br
I
Ph
2n 56%
2o 59%
2p 57%
2q 60%
1
2
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3
00
13
46
38
63
61
51
48
43
21
00
OCOPh
F3C
OCOPh
OCOPh
OCOPh
O
O
O
N
O
60
N
H
N
H
N
H
H
N
N
N
N
F3C
F3CO
3
90
MeO2C
CF3
2r 60%
2u 58%
2s 60%
2t 60%
4
Reflux
90
5c
6
OCOPh
OCOPh
OCOPh
O
O
O
N
N
N
90
H
H
H
N
O
N
N
O2N
7
FeBr3
90
2v 55%
2w 57%
2x 60%
8
Fe(OTf)3
Fe(acac)3
FeCl2
90
O
F
9
90
O
O
O
O
O
O
O
O
O
O
O
O
Cl
10
11
90
N
R2
R2
N
H
R2
N
R2
N
H
H
H
N
N
N
N
-
90
3a 70%
3b 72%
3c 66%
3d 63%
R2 = 4-Me-C6H4
aReagents and conditions: unless otherwise specified, a mixture of 1a (1.0 mmol),
catalyst (20 mol %), BP (2.5 mmol) in toluene (5.0 mL) was stirred at 90 °C for 24 h
under open air. bIsolated yield, [c]Portion wise addition of BP.
Cl
Cl
NO2
O
O
O
O
O
O
O
O
CF3
O
O
O
Cl
O
N
R2
N
R2
N
H
R2
N
R3
H
H
H
N
N
N
N
elevating the temperature to 60 °C, the desired product 2a
was formed in low yields (13%) despite prolonged reaction
times (Table 1, entry 2). Further increase of reaction
temperature (90 °C) improved the yields to 46% whereas
refluxing decreased the yields of 2a (38%) accompanied by the
formation of capricious complex mixtures and benzoic acid
(entry 3 and 4). However the product yields were significantly
improved with portion wise addition of BP (2.5 mmol, 5 × 0.5
equiv/0.5 h) at 90 °C temperature to a mixture of 1a and iron
catalyst in toluene (entry 5). Portion wise addition of peroxide
also ensures safety handling. Among several solvents tested,
toluene was found to be the most effective under the
optimized conditions.11 Although other iron salts could
catalyse the reaction, FeCl3·6H2O was superior (Table 1, entry
6-10).
3e 58%
3h 53%
R3 = 8-Aminoquinoline
3g 63%
3f 63%
aReaction conditions: 1a (1.0 mmol), BP (2.5 mmol, 5 × 0.5 equiv./0.5 h) in toluene (5.0
mL) was stirred at 90 °C for 24 h open air. All are isolated yields.
With these optimized conditions in hand we then explored the
substrate scope with electronically differentiated carboxamides
(aromatic, aliphatic and heteroaryl) and acyl peroxides.
The substrates with electron donating methyl, methoxy groups
on the para-position furnished the desired products in good
yields 63%, 70% (Scheme 2, 2a
substituted benzamides also produced relatively good yields of
the product in 61%, 65% (Scheme 2, 2c 2d). Further 3,4-
, 2b). 3-Methyl and 3,5-dimethyl
,
dimethoxy substrate afforded the benzoxylated product in
73% yield (Scheme 2, 2e). The unsubistituted benzamide with
2-methyl subistitution on quinoline ring produced 61% of the
corresponding product. (Scheme 2, 2f). In contrast, the mono,
di and tri-halo substituted systems underwent the chelation
assisted benzoxylation reaction with moderate yields. (Scheme
The role of metal contaminants in FeCl3 was ruled out from the
low yield outcome, when the reactions employed copper and
palladium salts.11, 12 In the absence of catalyst, the reaction did
not proceed (Table 1, entry 11). The variation of catalyst
loading, effect of co-oxidant and other reaction conditions
2 | J. Name., 2012, 00, 1-3
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2, 2g-2p). It is noteworthy that the ortho-fluoro (2g), 2,4,6-
trichloro (2m) and ortho-bromo (2n) substituted benzamides
didn’t show steric effect for the chelation.
The e-withdrawing substituents such as 4-ph, 4-CF3, 3,5-
bistrifloromethyl, 4-OCF3, 4-CO2Me and 4-NO2 benzamides
afforded the desired products in moderate to good yields
Figure 1. Crystal structure of 2g.
under standerd reaction conditions (Scheme 2, 2q-2v). The
heteroaryl, furyl moiety produced the corresponding C5-
benzoxylated product in 57% yield (Scheme 2, 2w). 8-
Acetamidoquinoline produced the desired product in 60%
yield (Scheme 2, 2x). Various substituted aryl acyl peroxides
(with e-releasing/withdrawing groups) employed for the
remote C-H functionalization resulted in the formation of the
corresponding coupling products in moderate to good yields
ranging 58-72% (Scheme 2 3a-3h). The synthetic value of the
remote oxygenation reaction is reflected from the tolerance of
halogens demonstrating that these halogens could be used as
handles for further functional group transformations.
Interestingly the 8-aminoquinoline urea under standard
reaction conditions underwent mono benzoxylation to furnish
the oxygenated urea derivative 3h in 53% yield. The
dibenzoxylation product did not form even when excess
peroxide (5equiv.) was used.
In order to probe the mechanistic path way, the reaction of 1a
in the presence of radical trappers i.e., TEMPO and 1,1-
Diphenylethylene were investigated (Scheme 4).
Scheme 4. Mechanistic investigations.
The iron catalyzed C5-oxygenation reaction on 8-
amidoquinoline with mixed peroxide was carried out under
standard reaction conditions employing aryl-alkyl acyl
peroxides i.e., benzyl acetyl- and benzyl t-butyl peroxides. In
both the cases the products obtained were corresponding to
arylacyl oxygenated 8-amidoquinoline 2a in 38% yield while
the formation of the alkyl acyloxy product was not observed.
Acetyl peroxide and TBHP failed to afford the expected
oxygenated product under standard reaction conditions
(Scheme 3). All the new compounds have been fully
characterized with 1HNMR, 13CNMR, HRMS. Further the
structure of the oxygenated product 2g was unambiguously
confirmed by single crystal X-ray analysis. (Fig. 1)
The diminished product yield in the presence of TEMPO, and
the formation of benzyloxy radical trapping product with 1,1-
diphenyl ethylene indicate that the reaction proceeds through
radical pathway.4f
Scheme 5. Substrates resistant to C5-Benzoxylation.
Scheme 3. C5-Benzoxylation with mixed acylperoxides and ter-
Butylhydroperoxide: a
It is also noteworthy that C5-benzoxylation reaction does not
proceed with the substrates 5a-5i (Scheme 5). This observation
infers that chelation is important to effect the reaction.
Based on these results and literature reports, we propose a
possible pathway for the C5-benzoxylation of 8-
a The reaction was performed with 1a (1.0 mmol), FeCl3.6H2O (0.2 mmol), acyl peroxide
(2.5 mmol 5 × 0.5 equiv./0.5 h) in toluene (5 mL) the reaction mixture was stirred at 90
°C for 24 h in open air all are Isolated yields.
amidoquinolines, presumably governed by a single-electron
transfer (SET) mechanism (Scheme 6).4f,7c,10c,
13
The initial
coordination of 8-amidoquinoline with FeCl3 and subsequent
deprotonation produced the chelated intermediate . The
A
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benzoyloxy radical formed by the homolytic cleavage of (multiplicity, coupling constant, number of hydrogen atoms).
Benzoyperoxide then attacks the intermediate at C5 position Multiplicity is abbreviated as follows: s (singlet), d (doublet), t
to form the complex . Thereafter, Fe(II) complex is oxidized (triplet), q (quartet), m (multiplet). Mass spectra were carried
in presence of benzyl peroxide followed by the generation of out with a Quattro LC triple-quadrupole mass spectrometer
complex through a proton transfer process. Finally, the (Micromass, Manchester, UK). High-resolution mass spectra
decomposition of provides the C5-benzoxylated product, were determined with a Quadrupole time-of-flight (Q-TOF)
along with the regeneration of intermediate to continue the mass spectrometer (QSTARXL, Applied Biosystems/MDS Sciex,
A
B
B
D
D
A
catalytic cycle. Further mechanistic studies are under way.
Foster city, USA).
General procedure for synthesis of 8-Amidoquinolines (1a-1x):8j
Scheme 6. Proposed mechanism.
The 8-aminoquinoline (288 mg, 2.0mmol) and triethylamine
(0.30 mL, 2.2mmol) were dissolved in dry CH2Cl2 (5 mL) and
stirred at room temperature for 10 min and the reaction
solution was cooled in an ice bath. The benzoyl chloride (0.23
mL 2.0mmol) was added drop wise (Note: If benzoyl chloride
derivative used was a solid, it was dissolved in a minimum
volume (3-4 mL) of dry CH2Cl2). The reaction solution was
allowed to come to room temperature while stirring overnight
(12h). The reaction mixture dissolved in EtOAc (20mL) water
(10mL). The organic layer was washed with 1.0 M NaOH
aqueous solution (3 X 15 mL), dried with anhydrous MgSO4,
filtered and roto-evaporated to give crude-product. The crude
mixture was purified by silica gel column chromatography with
hexane/EtOAc eluent. Yield (426.56 mg, 86% yield). All
products are colourless solids.
O
O
Ph
Ph
O
Ph
O
O
O
H
O
Ph
FeCl3
HCl
O
N
N
N
FeIII
A
SET
HN
O
O
FeII
B
O
N
N
R
R
O
R
BP
Fe III
Ph
Fe II
Ph
O
O
N
O
Ph
O
O
Cl
O
H
N
N
FeCl3
HN
FeIII
N
O
FeIII
C
O
N
D
R
R
R
General procedure for synthesis of acylperoxides (1aa-1ag): 13
Conclusions
Hydrogen peroxide (1.669 g, 35 wt. % in H2O, 17.18 mmol) was
added dropwise over 10 min to a cold (ice bath) solution of
acid chloride (30mmol) in diethyl ether (7 mL), followed by
dropwise addition of an aqueous solution of NaOH (1.517g,
37.93mmol, 10 mL) over 20 min. The resulting white
precipitate was collected by filtration. After washing with
water (3 × 5 mL) and diethyl ether (3 × 5 mL), the solid was
crystallized from a cold acetone / water mixture (1: 3 v/v).
General procedure for Benzoxylation of 8-amidoquinolines:
In summary, we have developed a simple and efficient
reaction for the oxygenation of C5-H bonds that are
geometrically inaccessible in 8-amidoquinolines with
inexpensive and nontoxic iron (III) catalyst. Large substrate
scope and high functional group tolerance has been
demonstrated for the C5 oxygenation reaction. The tolerance
of halogens on either of the rings demonstrate that these
halogens could be used as handles for further functional group
transformations. The reaction is iodine, silver, acid, additive
free and is not sensitive to air or moisture. The high
regioselectivity of the reaction is reflected from the exclusive
formation of C5-benzoxylation product. The results presented
would open up new avenues for the synthesis of biologically
active quinolines.
A 10 mL round-bottomed flask was charged with 4-methyl-N-
(quinolin-8-yl)benzamide (1a) (262 mg, 1.0 mmol) and
FeCl3·6H2O (32 mg, 20 mol %) in toluene (3 mL). To the
resulting mixture was added benzoyl peroxide (605 mg, 2.5
mmol, 5 × 0.5 equiv./0.5 h) portion wise. Once the addition
was completed, the resulting solution was stirred at 90 °C in
open air for 24 h (reaction monitored by TLC). The crude
compound obtained was washed with a saturated aqueous
solution of NaHCO3 to remove the unwanted benzoic acid
formed, and then extracted with ethyl acetate. The combined
organic layers were dried with Na2SO4, and the solvent was
evaporated under reduced pressure. The crude product was
purified by column chromatography (hexane/ethyl acetate) to
obtain the desired product as white solid, 239 mg (yield 63%).
General procedure for synthesis 1,3-di(quinolin-8-yl)urea (1y): 6
Experimental section
General
All commercially available chemicals were used as received.
Benzoyl peroxide was purchased from S.D Fine-Chemicals.
Thin-layer chromatography plates were visualized by exposure
to UV or Iodine, and/or by immersion in an acidic staining
solution of phosphomolybdic acid followed by heating on a hot
1
plate. H NMR spectra were obtained with 300, 400 and 500
MHz spectrometers, 13C NMR spectra were obtained with 100
Dry triethylamine (1.5 mL, 11 mmol) was added to a solution
of 8-aminoquinoline (720 mg, 5.0 mmol) in dry
dichloromethane (8ml), and then a solution of triphosgene (2.0
mg, 0.006 mmol) in small amount of dichloromethane was
added under ice bath condition, sealed and stirred it
overnight, the solvent was evaporated to dryness and the
and 125 MHz spectrometers in CDCl3 at 298
K with
tetramethylsilane and CDCl3 as the internal standard. Chemical
shifts (δ) are reported in ppm relative to the residual solvent
signal (δ = 7.26 ppm for 1H NMR and δ = 77.0 ppm for 13C
NMR). Data for 1H NMR are reported as follows: chemical shift
4 | J. Name., 2012, 00, 1-3
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residue was purified by column chromatography. White Solid, Pale yellow Solid, 100 mg (73% yield), mp: 218-222 °C. 1H NMR
184 mg (yield 58%), mp: 173-175 °C. 1H NMR (400MHz, (500MHz, CDCl3): δ = 10.65 (Br s, 1H), 8.99 (d, J= 8.64Hz, 1H),
CDCl3+CD2Cl2): δ = 9.52 (s, 2H), 8.83-8.80 (m, 2H), 8.71-8.69 8.91-8.88 (m,1H), 8.34-8.25 (m, 3H), 7.73-7.66 (m, 3H),7.61-
(m, 2H), 7.59-7.55 (m, 2H), 7.47-7.44 (m, 4H). 13C NMR (100 7.56 (m, 2H), 7.53-7.48 (m, 2H), 7.02 (d, J= 8.92 Hz, 1H), 4.02
MHz, CDCl3): δ = 152.16, 147.75, 138.31, 136.39, 135.48, (s, 3H), 3.98 (s, 3H).13C NMR (100 MHz, CDCl3): δ = 165.25,
128.07, 127.52, 121.49, 120.07, 115.16. ESI-MS: m/z 315 164.97, 152.16, 149.21, 148.64, 140.75, 139.06, 133.98,
(M+H) +.
133.08, 130.61, 130.32, 128.97, 128.78, 127.71, 122.21,
121.89, 119.81, 119.58, 115.75, 110.89, 110.46, 56.09, 56.08.
2,4,6-trichlorobenzoic peroxyanhydride (1ae)
+
ESI-MS: m/z 429 (M+H) . ESI-HRMS: calcd for C25H21O5N2 =
White Solid, 146 mg (yield 80%), mp: 114-116 °C. 1H NMR
(400MHz, CDCl3): δ = 7.43 (s, 4H). 13C NMR (100 MHz, CDCl3):
δ = 159.27, 138.58, 134.48, 128.46, 126.36.
429.14450, Found 429.14328.
8-benzamido-2-methylquinolin-5-yl benzoate (2f)
8-(4-methylbenzamido)quinolin-5-yl benzoate (2a)
Pale yellow semi solid, 88.5 mg (61% yield), mp: 163-167 °C. 1H
1
White Solid, 91.4 mg (yield 63%), mp: 143-147 °C. H NMR NMR (400MHz, CDCl3+CD2Cl2): δ = 10.75 (Br s, 1H), 8.97 (d,
(400MHz,CDCl3+CD2Cl2): δ = 10.67 (Br s, 1H), 9.01 (d, J= J=8.55Hz, 1H), 8.33-8.30 (m,2H), 8.13 (d, J=8.55Hz, 1H), 8.11-
8.43Hz, 1H), 8.91-8.89 (m,1H), 8.34-8.30 (m, 2H), 8.28-8.25 (m, 8.08 (m, 2H),7.73-7.67 (m,1H),7.61-7.55 (m, 5H), 7.42 (d,
1H), 8.00 (d, J = 8.19Hz, 2H), 7.74-7.68 (m,1H), 7.61-7.56 (m, J=8.55Hz, 1H), 7.37 (d, J=8.55Hz, 1H), 2.79 (s, 3H).13C NMR
2H), 7.53-7.48 (m, 2H), 7.36 (d, 2H), 2.47 ( s, 3H). 13C NMR (100 (100 MHz, CDCl3): δ = 165.25, 157.82, 141.07, 138.56, 135.18,
MHz, CDCl3): δ = 165.36, 165.24, 148.63, 142.39, 140.80, 133.90, 132.28, 131.79, 130.67, 130.29, 128.82, 128.74,
139.08, 133.96, 133.07, 132.21, 130.58, 130.32, 129.46, 127.22, 122.73, 120.27, 118.48, 115.95, 25.40. ESI-MS: m/z
128.98, 128.78, 127.29, 122.19, 121.88, 119.56, 115.88, 383 (M+H) +. ESI-HRMS: calcd for C24H19O3N2 = 383.1408,
+
21.54.ESI-MS: m/z 383 (M+H)
. ESI-HRMS: calcd for Found 383.1404.
C24H19O3N2 = 383.13902, Found 383.14080.
8-(2-fluorobenzamido)quinolin-5-yl benzoate (2g)
1
Pale yellow Solid, 83.8 mg (57% yield), mp: 193-197°C. H
8-(4-methoxybenzamido)quinolin-5-yl benzoate (2b)
1
Pale yellow solid, 100 mg (yield 70%), mp: 272-276 °C. H NMR NMR (500MHz, CDCl3+ CD2Cl2): δ =11.14 (Br d, J = 12.66 Hz,
(400MHz, CDCl3+ CD2Cl2): δ = 10.62 (Br s, 1H), 8.98 (d, 1H), 9.05 (d, J = 8.39 Hz, 1H), 8.96-8.88 (m, 1H), 8.33-8.31 (m,
J=8.39Hz, 1H), 8.90-8.88 (m,1H), 8.32-8.30 (m, 2H), 8.27-8.24 1H), 8.29-8.21 (m, 2H), 8.13-8.10 (m, 1H) , 7.74-7.68 (m, 1H),
(m, 1H), 8.08-8.30 (m, 2H), 7.72-7.68 (m, 1H), 7.60-7.55 (m, 7.64-7.53 (m, 3H), 7.52-7.47 (m, 2H), 7.38-7.31 (m, 1H), 7.29-
2H), 7.51-7.47 (m, 2H), 7.07-7.02 (m, 2H), 3.90 (s, 3H). 13C NMR 7.23 (m, 1H). 13C NMR (100 MHz, CDCl3): δ = 165.19, 161.80,
(100 MHz, CDCl3): δ = 165.21, 164.88, 162.50, 148.57, 140.67, 161.53, 148.80, 141.18, 139.14, 133.97, 133.67, 133.58,
138.98, 133.92, 133.04, 130.52, 130.26, 129.11, 128.92, 133.16, 132.04, 130.30, 128.94, 128.77, 124.85, 122.14,
+
128.74, 128.40, 127.20, 122.12, 121.84, 119.49, 115.72, 121.91, 119.43, 116.44, 116.20. ESI-MS: m/z 387 (M+H) . ESI-
+
113.96, 55.42. ESI-MS: m/z 399 (M+H) . ESI-HRMS: calcd for HRMS: calcd for C23H16FN2O3= 387.1167, Found 387.1168.
C24H19O4N2 = 399.13393, Found 399.13549.
8-(3,4-difluorobenzamido)quinolin-5-yl benzoate (2h)
1
8-(3-methylbenzamido)quinolin-5-yl benzoate (2c)
Yellow Solid, 81.8 mg (58% yield), mp: 152-154°C. H NMR
Yellow Solid, 88.5 mg (61% yield), mp: 184-188°C.1H NMR (400MHz, CDCl3): δ =10.63 (Br s,1H), 8.95 (d, J = 8.55Hz, 1H),
(500MHz,CDCl3+ CD2Cl2): δ = 10.66 (Br s, 1H), 9.01 (d, 1H), 8.92-8.89 (m, 1H), 8.33-8.30 (m, 2H), 8.29-8.27 (m, 1H),7.97-
8.92-8.90 (m, 1H),8.34-8.30 (m, 2H), 8.29-8.26 (m, 1H),7.91- 7.91 (m,1H) , 7.88-7.83 (m, 1H), 7.74-7.69 (m, 1H), 7.61-7.56
7.86 (m, 2H), 7.73-7.69 (m, 1H), 7.60-7.57 (m, 2H), 7.53-7.49 (m, 2H), 7.54-7.49 (m, 2H), 7.38-7.31 (m, 1H). 13C NMR (100
(m, 2H), 7.47-7.43 (m, 1H), 7.38-7.36 (m, 1H), 2.50 (s, 3H). 13C MHz, CDCl3): δ = 165.85, 148.28, 138.42, 136.35, 133.88,
NMR (100 MHz, CDCl3): δ = 165.60, 165.23, 148.67, 140.87, 132.02, 127.81, 127.15, 123.53, 121.97, 121.71, 117.62,
+
139.09, 138.68, 135.02, 133.97, 133.01, 132.63, 130.59, 117.43, 117.04, 116.85, 116.40. ESI-MS: m/z 405 (M+H) . ESI-
130.31, 128.77, 128.04, 124.19, 122.19, 121.89, 119.54, HRMS: calcd for C23H15O3N2F2 = 405.10453, Found 405.10574.
+
115.97, 21.47. ESI-MS: m/z 383 (M+H) . ESI-HRMS: calcd for 8-(4-chlorobenzamido)quinolin-5-yl benzoate (2i)
Yellow Solid, 84.6 mg (60% yield), mp: 103-106°C. 1H NMR (400
C24H19O3N2 = 383.13902, Found 383.13840.
8-(3,5-dimethylbenzamido)quinolin-5-yl benzoate (2d)
MHz, CDCl3): δ =10.66 (Br s, 1H), 8.98 (d, J = 8.43Hz, 1H), 8.91-
1
White Solid. 93.0 mg (65% yield), mp: 146-150 °C. H NMR 8.89 (m, 1H), 8.34-8.30 (m, 2H), 8.30-8.26 (m, 1H), 8.05-8.02
(300MHz,CDCl3): δ = 10.61 (Br s, 1H), 9.01 (d, J=8.68Hz, 1H), (m, 2H), 7.74-7.69 (m,1H), 7.61-7.58 (m, 2H), 7.55-7.49 (m,
8.92-8.89(m,1H), 8.35-8.25 (m, 3H), 7.74-7.66 (m,3H), 7.61- 4H). 13C NMR (125 MHz, CDCl3): δ = 165.19, 164.21, 148.74,
7.47(m, 4H), 7.27-7.20 (m, 1H), 2.45 (s, 6H).13C NMR (125 MHz, 141.10, 139.01, 138.18, 134.01, 133.39, 132.66, 130.67,
CDCl3): δ = 165.82, 165.23, 148.66, 140.82, 139.10, 138.48, 130.31, 129.06, 128.79, 128.70, 122.22, 121.98, 119.52,
135.07, 133.96, 133.52, 133.08, 130.56, 130.31, 128.98, 116.05. ESI-MS: m/z 403 (M+H) +. ESI-HRMS: calcd for
128.77, 125.01, 122.18, 121.86, 119.54, 115.98, 21.36. ESI-MS: C23H16O3N2Cl = 403.0844, Found 403.0847.
m/z 397 (M+H) +. ESI-HRMS: calcd for C25H21O3N2 = 397.15467, 8-(3-chlorobenzamido)quinolin-5-yl benzoate (2j)
Yellow Solid, 84.6 mg (60% yield), mp: 123-125°C. 1H NMR (400
Found 397.15604.
8-(3,4-dimethoxybenzamido)quinolin-5-yl benzoate (2e)
MHz, CDCl3+ CD2Cl2): δ =10.64 (Br s,1H), 8.97 (d, J = 8.55 Hz,
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1H), 8.92-8.89 (m, 1H), 8.33-8.30 (m, 2H), 8.29-8.26 (m, 1H), (m, 3H).13C NMR (100 MHz, CDCl3): δ = 165.17, 164.30, 148.73,
8.13-8.09 (m, 1H), 8.08-8.06 (m,1H), 7.97-7.94 (m,1H), 7.73- 141.10, 138.97, 134.00, 133.81, 132.61, 132.02, 130.65,
7.69 (m, 1H), 7.60-7.56 (m, 3H), 7.51-7.49 (m, 2H). 13C NMR 130.29, 128.84, 126.65, 122.19, 121.97, 119.50, 116.04. ESI-
(125 MHz, CDCl3): δ = 165.17, 163.90, 148.79, 141.19, 138.99, MS: m/z 447 M+. ESI-HRMS: calcd for C23H16O3N2Br =
136.74, 135.02, 134.00, 133.62, 132.53, 131.90, 130.65, 447.03388, Found 447.0847.
8-(4-iodobenzamido)quinolin-5-yl benzoate (2p)
130.30, 130.07, 128.77, 128.40, 127.67, 125.22, 122.19,
+
119.47, 116.16.ESI-MS: m/z 403 (M+H) . ESI-HRMS: calcd for
White Solid, 75.8 mg (57% yield), mp: 218-222 °C. 1H NMR (500
MHz, CDCl3): δ = 10.65 (Br s,1H), 8.97 (d, J=8.39 Hz, 1H), 8.90-
8.88 (m, 1H), 8.33-8.30 (m, 2H), 8.29-8.26 (m, 1H), 7.93-7.90
(m,2H), 7.82-7.79 (m, 2H), 7.73-7.69 (m, 1H), 7.60 -7.56 (m,
2H), 7.53-7.48 (m, 2H).13C NMR (125 MHz, CDCl3): δ = 165.19,
164.52, 148.77, 141.19, 139.01, 138.04, 134.44, 134.01,
132.64, 130.67, 130.31, 128.83, 122.22, 121.99, 119.52,
C23H16O3N2Cl = 403.0844, Found 403.0847.
8-(3,5-dichlorobenzamido)quinolin-5-yl benzoate (2k)
Yellow Solid, 84.0 mg (60% yield), mp: 206-208°C. 1H NMR (300
MHz, CDCl3+CD2Cl2): δ =10.60 (Br s, 1H), 8.97-8.92 (m, 2H),
8.35-8.25 (m, 3H), 7.98-7.92 (m, 2H), 7.75-7.69 (m, 1H), 7.62-
7.49 (m, 5H). 13C NMR (125 MHz, CDCl3): δ = 165.08, 162.46,
148.88, 141.39, 138.90, 137.81, 135.64, 134.01, 132.18,
131.68, 130.67, 130.27, 129.20, 128.77, 125.83, 124.78,
+
116.07, 98.99. ESI-MS: m/z 495 (M+H) . ESI-HRMS: calcd for
+
C23H16I N2O3 = 495.0215, Found 495.0212.
122.17, 122.05, 119.40, 116.29. ESI-MS: m/z 437 (M+H) . ESI-
8-([1,1'-biphenyl]-4-ylcarboxamido)quinolin-5-yl benzoate (2q)
HRMS: calcd for C23H15O3N2Cl2 = 437.04542, Found 437.04644.
1
Pale yellow Solid, 83.0 mg (60% yield), mp: 220-224 °C. H
8-(3,4-dichlorobenzamido)quinolin-5-yl benzoate (2l)
Yellow Solid, 82.6 mg (59% yield), mp: 138-140°C. 1H NMR (500
MHz, CDCl3+CD2Cl2): δ =10.63 (Br s,1H), 8.95 (d, J = 8.54 Hz,
1H), 8.92-8.90 (m, 1H), 8.32 (d, J = 7.47Hz, 2H),8.30-8.27 (m,
1H),8.18-8.17 (m,1H), 7.92-7.89 (m, 1H), 7.73-7.69 (m, 1H),
7.65-7.62 (m, 1H), 7.61-7.57 (m, 2H), 7.54-7.49 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ = 165.14, 162.92, 148.83, 141.29,
138.94, 136.34, 134.75, 134.03, 133.36, 132.34, 130.78,
130.30, 129.54, 128.84, 126.22, 122.19, 122.04, 119.46,
116.17.ESI-MS: m/z 437 (M+H) +. ESI-HRMS: calcd for
C23H15O3N2Cl2 = 437.04542, Found 437.04737.
NMR (500MHz,CDCl3+CD2Cl2): δ = 10.75 (Br s, 1H), 9.04 (d,
J=8.43Hz, 1H), 8.93-8.88 (m,1H), 8.35-8.30 (m, 2H), 8.29-8.25
(m, 1H), 8.18 (d, J=8.19Hz, 2H), 7.79 (d, J=8.19Hz, 2H), 7.74-
7.66 (m, 3H), 7.61-7.56 (m, 2H), 7.53-7.48 (m, 4H), 7.44-7.39
(m, 1H). 13C NMR (100 MHz, CDCl3): δ = 165.23, 165.07,
148.70, 144.68, 140.93, 140.01, 133.09, 133.97, 133.66,
130.63, 130.31, 128.94, 128.78, 128.04, 127.82, 127.46,
+
127.24, 121.93, 119.56, 115.99. ESI-MS: m/z 445 (M+H) . ESI-
HRMS: calcd for C29H21N2O3 = 445.1563, Found 445.1562.
8-(4-(trifluoromethyl)benzamido)quinolin-5-yl benzoate (2r)
1
Yellow Solid, 84.0 mg (60% yield), mp: 167-169 °C. H NMR
8-(2,4,6-trichlorobenzamido)quinolin-5-yl benzoate (2m)
Brown Solid, 76.6 mg (58% yield), mp: 159-163°C. 1H NMR (400
MHz, CDCl3): δ = 10.01 (Br s,1H), 9.00 (d, J = 8.43Hz, 1H), 8.83-
8.81 (m, 1H), 8.34-8.31 (m, 2H), 8.29-8.26 (m, 1H), 8.12-8.09
(m, 1H), 7.74-7.69 (m,1H), 7.61-7.56 (m, 2H), 7.51-7.48 (m,
2H), 7.43-7.42 (m, 1H). 13C NMR (125MHz, CDCl3): δ = 165.17,
161.72, 148.85, 141.70, 138.77, 136.10, 134.69, 134.06,
133.68, 133.25, 132.07, 130.72, 130.34, 130.14, 128.80,
128.44, 128.30, 122.24, 122.04, 119.49, 116.83. ESI-MS: m/z
471 M+. ESI-HRMS: calcd for C23H14O3N2Cl3 = 471.00645, Found
471.00820.
(400 MHz, CDCl3): δ = 10.73 (Br s, 1H),8.99 (d, J=8.43 Hz, 1H),
8.92-8.88 (m, 1H), 8.34-8.28 (m, 3H), 8.20 (d, J = 8.06 Hz, 2H),
7.83 (d, J = 8.31 Hz, 2H), 7.74-7.69 (m, 1H), 7.61-7.57 (m, 2H),
7.55-7.50 (m, 2H). 13C NMR (100 MHz, CDCl3): δ = 165.19,
163.96, 148.83, 141.83, 141.33, 139.03, 138.28, 134.05,
132.47, 130.74, 128.84, 127.53, 125.90, 122.25, 122.06,
+
119.52, 116.23. ESI-MS: m/z 475 (M+K) . ESI-HRMS: calcd for
C24H16O3N2F3 = 437.1108, Found 437.1103.
8-(3,5-biS(trifluoromethyl)benzamido)quinolin-5-yl benzoate (2s)
Yellow Solid, 78.6 mg (60% yield), mp: 176-180°C.1H NMR (500
MHz, CDCl3): δ = 10.76 (Br s, 1H), 8.97 (d, J = 8.39 Hz, 1H), 8.95-
8.93 (m, 1H), 8.52-8.51(m, 2H), 8.34-8.31 (m, 3H), 8.12-8.10
(m, 1H), 7.74-7.70 (m, 1H), 7.62-7.52 (m, 4H).13C NMR (100
MHz, CDCl3): δ = 165.16, 162.25, 149.09, 141.70, 139.00,
137.18, 134.10, 130.84, 130.35, 128.84, 127.53, 125.40,
8-(2-bromobenzamido)quinolin-5-yl benzoate (2n)
1
Brown Solid, 82.0 mg (59% yield), mp: 149-151 °C. H NMR
(500 MHz, CDCl3): δ = 10.26 (Br s, 1H), 9.03-9.01(m, 1H), 8.85-
8.83 (m, 1H), 8.33-8.31 (m, 2H), 8.28-8.25 (m, 1H), 7.74-7.69
(m, 3H), 7.60-7.51 (m, 2H), 7.52-7.47 (m, 3H), 7.38-7.35 (m,
1H).13C NMR (100 MHz, CDCl3): δ = 171.56, 165.81, 148.74,
141.28, 138.90, 138.90, 138.12, 133.98, 133.63, 132.59,
131.50, 130.54, 130.29, 130.10, 129.55, 129.34, 128.86,
128.76, 128.39, 127.62, 127.13, 126.23, 122.16, 121.93,
119.64, 119.45, 116.38. ESI-MS: m/z 447 M+. ESI-HRMS: calcd
for C23H16O3N2Br = 447.03388, Found 447.03581.
+
122.21, 119.50, 116.54. ESI-MS: m/z 505 (M+H) . ESI-HRMS:
calcd for C25H15F6N2O3 = 505.0998, Found 505.0994.
8-(4-(trifluoromethoxy)benzamido)quinolin-5-yl benzoate (2t)
1
Yellow Solid, 81.6 mg (60% yield), mp: 144-146 °C. H NMR
(400 MHz, CDCl3): δ = 10.67 (Br s, 1H), 8.98 (d, J =8.54Hz, 1H),
8.92-8.88 (m,1H), 8.37-8.25 (m, 3H), 8.15 (d, J = 8.54 Hz, 2H),
7.74-7.69 (m, 1H),7.61-7.56 (m, 2H),7.54-7.49 (m, 2H), 7.40 (d,
J = 8.39Hz, 2H).13C NMR (100 MHz, CDCl3): δ = 151.78, 148.77,
134.03, 130.71,130.32, 129.20, 128.80, 122.01, 120.83, 119.54,
116.09. ESI-MS: m/z 453 (M+H) +. ESI-HRMS: calcd for
C24H16F3N2O4= 453.1085, Found 453.1084.
8-(4-bromobenzamido)quinolin-5-yl benzoate (2o)
1
Brown Solid, 82.0 mg (59% yield), mp: 173-177 °C. H NMR
(400 MHz, CDCl3+ CD2Cl2): δ = 10.66 (Br s, 1H), 8.98 (d, J =
8.55Hz, 1H), 8.91-8.88 (m,1H), 8.35-8.26 (m, 3H), 7.96 (d, J =
8.43Hz, 2H), 7.71-7.69 (m, 2H), 7.61-7.56 (m, 2H), 7.54-7.48
6 | J. Name., 2012, 00, 1-3
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1
Methyl 4-((5-(benzoyloxy)quinolin-8-yl)carbamoyl)benzoate (2u)
Yellow Solid, 113.0 mg (72% yield), mp: 157-159°C. H NMR
(500 MHz, CDCl3): δ = 10.65 (Br s, 1H), 8.99 (d, J = 8.43 Hz, 1H),
8.93-8.83 (m, 1H), 8.34-8.17(m, 3H), 7.99(d, J = 7.82 Hz, 2H),
7.55-7.44 (m, 2H), 7.36 (d, J = 7.70 Hz, 2H), 7.05 (d, J = 8.43 Hz,
2H), 3.93 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3): δ =
165.32, 164.95, 164.18, 148.57, 142.39, 140.94, 139.06,
132.90, 132.44, 130.66, 129.43, 127.27, 122.30, 121.79,
121.18, 119.56, 115.89, 114.03, 55.56, 21.52. ESI-MS: m/z 413
White Solid, 81.8 mg (58% yield), mp: 204-208 °C. 1H NMR (500
MHz, CDCl3): δ = 10.74 (Br s, 1H), 9.00 (d, J=8.39 Hz, 1H), 8.92-
8.90 (m, 1H), 8.32 (d, J = 7.32 Hz, 2H), 8.30-8.27 (m, 1H) ,8.24-
8.21 (m, 2H), 8.16-8.14 (m, 2H), 7.73-7.69 (m,1H), 7.60-7.51
(m, 2H), 7.54-7.50 (m, 2H), 3.98 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ = 166.26, 165.17, 164.33, 148.80, 141.22, 139.03,
138.81, 134.01, 133.01, 132.57, 130.68, 130.30, 130.04,
128.19, 127.30, 122.01, 119.50, 116.16, 52.42. ESI-MS: m/z
+
(M+H) . ESI-HRMS: calcd for C25H21O4N2 = 413.14958, Found
+
413.15062.
427 (M+H) . ESI-HRMS: calcd for C25H19O5N2 = 427.12885,
8-(4-methylbenzamido)quinolin-5-yl 4-fluorobenzoate (3c)
Found 427.12953.
8-(4-nitrobenzamido)quinolin-5-yl benzoate (2v)
1
Pale yellow Solid, 100 mg (66% yield), mp: 218-222°C. H NMR
(500 MHz, CDCl3): δ =10.66 (Br s, 1H), 9.00 (d, J = 8.54Hz, 1H),
8.92-8.89 (m, 1H), 8.36-8.32 (m, 2H), 8.26-8.22 (m, 1H), 7.99
(d, J= 8.08 Hz, 2H), 7.53-7.47 (m, 2H), 7.36 (d, J = 7.78 Hz, 2H),
7.27-7.23 (m, 2H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3): δ =
165.38, 164.29, 148.67, 142.44, 140.61, 139.05, 133.01,
132.14, 130.47, 129.47, 127.28, 125.18, 121.93, 119.56,
Yellow Solid, 77.0 mg (55% yield), mp: 183-187°C.1H NMR (400
MHz, CDCl3+ CD2Cl2): δ = 10.77 (Br s, 1H), 8.99 (d, J = 8.54 Hz,
1H), 8.93-8.90 (m, 1H), 8.47-8.38 (m, 2H), 8.34-8.29 (m, 2H),
8.28-8.22 (m, 2H), 7.74-7.70 (m, 1H), 7.61-7.51 (m, 5H).13C
NMR (100 MHz, CDCl3): δ = 165.16, 163.11, 149.77, 148.93,
141.57, 140.41, 138.97, 134.09, 133.71, 130.82, 130.31,
130.14, 128.81, 128.44, 124.03, 122.27, 122.14, 119.49,
116.43. ESI-MS: m/z 414 (M+H) +. ESI-HRMS: calcd for
C23H16N3O5= 414.1091, Found 414.1085.
+
116.16, 115.84, 21.56. ESI-MS: m/z 401 (M+H) . ESI-HRMS:
calcd for C24H18O3N2F = 401.12960, Found 401.13077.
8-(4-methylbenzamido)quinolin-5-yl 2-chlorobenzoate(3d)
8-(furan-2-carboxamido)quinolin-5-yl benzoate (2w)
Pale yellow Solid, 99.5 mg (63% yield), mp: 127-131°C. 1H NMR
(500 MHz, CDCl3): δ = 10.68 (Br s, 1H), 9.01 (d, J = 8.43Hz, 1H),
8.92-8.90 (m, 1H), 8.36-8.33 (m, 1H) , 8.21-8.18 (m, 1H), 8.00
(d, J= 8.19 Hz, 2H), 7.59-7.52 (m, 4H), 7.49-7.44 (m, 1H), 7.36
(d, J = 7.94 Hz, 2H), 2.46 (s, 3H). 13C NMR (125 MHz, CDCl3): δ =
165.34, 164.14, 148.65, 142.41, 140.56, 139.03, 134.50,
133.52, 133.19, 132.14, 131.51, 130.65, 129.44, 128.81,
127.27, 126.90, 121.97, 119.42, 115.78, 21.52.ESI-MS: m/z 417
Yellow Liquid, 85.5 mg (57% yield),1H NMR (500 MHz,
CDCl3+CD2Cl2): δ = 10.72 (Br s, 1H), 8.96- 8.91 (m, 2H), 8.33-
8.30 (m, 2H), 8.28-8.25 (m, 1H), 7.72-7.68 (m, 1H),7.64 -
7.63(m, 1H), 7.52-7.47 (m, 2H), 7.33-7.31 (m, 1H), 6.62-6.58
(m, 1H). 13C NMR (100 MHz, CDCl3): δ = 165.18, 156.28,
148.79, 148.19, 144.53, 141.08, 138.93, 133.97, 132.49,
130.49, 130.28, 128.76, 122.17, 121.92, 119.40, 116.05,
+
+
(M+H) . ESI-HRMS: calcd for C24H18O3N2Cl = 417.10005, Found
115.22, 112.44. ESI-MS: m/z 359 (M+H) . ESI-HRMS: calcd for
417.10147.
8-(4-methylbenzamido)quinolin-5-yl 2,4,6-trichlorobenzoate (3e)
C21H15O4N2 = 359.10263, Found 359.10446.
8-acetamidoquinolin-5-yl benzoate (2x)
Brown Solid, 99.0 mg (60% yield), mp: 159-163°C. 1H NMR (500
MHz, CDCl3): δ = 9.74 (Br s, 1H), 8.85-8.81 (m, 2H), 8.30 (d, J =
7.47Hz, 2H), 8.24 (d, J = 8.54Hz, 1H), 7.72-7.68 (m, 1H), 7.59-
7.55 (m, 2H), 7.49-7.46 (m, 1H), 7.43 (d, J = 8.39Hz, 1H), 2.37
(s, 3H).13C NMR (125 MHz, CDCl3): δ = 168.67, 165.22, 148.49,
140.69, 138.54, 133.96, 132.85, 130.55, 130.29, 128.77,
122.08, 121.81, 119.46, 115.84, 25.08. ESI-MS: m/z 307 (M+H)
+. ESI-HRMS: calcd for C18H15O3N2 = 307.10772, Found
307.10714.
Yellow Solid, 106.7 mg (58% yield), mp: 212-214°C.1H NMR
(500 MHz, CDCl3): δ = 10.67 (Br s, 1H), 9.01 (d, J = 8.39Hz, 1H),
8.93-8.91 (m, 1H), 8.51-8.48 (m, 1H), 7.99 (d, J = 8.08 Hz, 2H) ,
7.59-7.55 (m, 2H), 7.51-7.49 (m, 2H), 7.36 (d, J = 7.93 Hz, 2H),
2.46 (s, 3H). 13C NMR (125 MHz, CDCl3): δ = 165.35, 162.69,
148.78, 142.48, 139.97, 138.94, 136.95, 133.64, 132.75,
132.08, 131.47, 130.49, 129.47, 128.30, 127.29, 122.13,
+
121.92, 119.32, 115.69, 21.54. ESI-MS: m/z 507 (M+Na) . ESI-
HRMS: calcd for C24H16O3N2Cl3 = 485.02210, Found 485.02219.
8-(4-methylbenzamido)quinolin-5-yl 4-methylbenzoate (3a)
8-(4-methylbenzamido)quinolin-5-yl 3-(trifluoromethyl)benzoate
(3f)
1
Yellow Solid, 105.0 mg (70% yield), mp: 182-186 °C. H NMR
(400 MHz, CDCl3): δ = 10.66 (Br s, 1H), 9.00 (d, J = 8.55 Hz, 1H),
8.91-8.88 (m, 1H), 8.28-8.24 (m, 1H), 8.21 (d, J =8.19Hz, 2H),
7.99 (d, J =8.19Hz, 2H), 7.52-7.46 (m, 2H), 7.40-7.34 (m, 4H),
2.50 (s, 3H), 2.47 (s, 3H).13C NMR (100 MHz, CDCl3): δ = 165.36,
148.59, 144.91, 142.38, 140.88, 139.04, 132.95, 132.20,
130.68, 130.70, 129.49, 127.29, 126.15, 122.25, 121.78,
1
Pale yellow Solid, 107.7 mg (63% yield), mp: 141-143°C. H
NMR (500 MHz, CDCl3): δ =10.68 (Br s, 1H), 9.02 (d, J = 8.54 Hz,
1H), 8.93-8.90 (m, 1H), 8.59-8.57 (m, 1H),8.50 (d, J= 7.78 Hz,
1H), 8.25-8.21(m, 2H), 8.01-7.95(m, 3H), 7.76-7.71 (m, 1H),
7.54-7.49 (m, 2H), 7.36 (d, J = 7.78 Hz, 2H), 2.46 (s, 3H).13C
NMR (100 MHz, CDCl3): δ = 163.99, 148.75, 142.50, 140.44,
139.04, 133.46, 133.28, 132.10, 131.71, 130.34, 129.87,
129.52, 127.29, 122.01, 119.51, 115.87, 21.52. ESI-MS: m/z
+
119.59, 115.93, 21.83,21.56. ESI-MS: m/z 397 (M+H) . ESI-
HRMS: calcd for C25H21O3N2 = 397.15467, Found 397.15398.
8-(4-methylbenzamido)quinolin-5-yl 4-methoxybenzoate (3b)
+
451 (M+H) . ESI-HRMS: calcd for C25H18O3N2F3 = 451.12640,
Found 451.12693.
8-(4-methylbenzamido)quinolin-5-yl 4-nitrobenzoate(3g)
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Yellow Solid, 102.6 mg (63% yield), mp: 194-198°C.1H NMR
(400 MHz, CDCl3): δ = 10.67 (Br s, 1H), 9.02 (d, J = 8.55 Hz, 1H),
8.96-8.87 (m, 1H),8.56-8.47 (m, 2H), 8.46-8.39 (m, 2H), 8.26-
8.18 (m, 1H),7.99 (d, J = 8.06Hz, 1H), 7.57-7.50 (m, 2H), 7.37(d,
J = 7.94 Hz, 2H), 2.47 (s, 3H). 13C NMR (125 MHz, CDCl3): δ =
148.81, 131.44, 130.18, 129.51, 127.30, 123.93, 122.08,
4
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+
119.51, 115.77, 29.69 ESI-MS: m/z 428 (M+H) . ESI-HRMS:
calcd for C24H18O5N3 = 428.12410, Found 428.12510.
8-(3-(quinolin-8-yl)ureido)quinolin-5-yl 4-methylbenzoate (3h)
White Solid. 75 mg (53% yield), mp: 197-199 °C. 1H NMR
(500MHz, CDCl3): δ = 9.52 (m, 2H), 8.82-8.78 (m, 1H), 8.75-8.69
(m, 2H), 8.23-8.15 (m, 3H), 7.60-7.55 (m, 1H), 7.47-7.35 (m,
6H), 2.49 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 165.42,
152.04, 148.16, 147.80, 144.82, 139.82, 138.51, 138.31,
136.41, 135.42, 133.75, 130.61, 130.35, 129.46, 128.09,
127.54, 126.25, 122.24, 121.74, 121.54, 120.13, 119.64,
5
6
7
W. Li, Z. Dong, J. Zhu, Q. Luo and J. Liu, Chem. Commun.,
2014, 50, 14744.
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+
115.16, 114.42, 21.80. ESI-MS: m/z 449 (M+H) . ESI-HRMS:
calcd for C27H21O3N4 = 449.16082, Found 449.16100.
Chem. Front., 2016, 3, 1309; (d) L. D. Tran, J. Roane and O.
Daugulis, Angew. Chem. Int. Ed. 2013, 52, 6043. (e) J. Liu, S.
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Conflicts of interest
There are no conflicts to declare.
8
(a) X. Cong and X. Zeng, Org. Lett. 2014, 16, 3716; (b) M. Cui,
J.-H. Liu, X.-Y. Lu, X. Lu, Z.-Q. Zhang, B. Xiao and Y. Fu,
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and M. Kanai, Org. Biomol. Chem., 2016, 14, 8092; (d) J. Xu,
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Acknowledgements
Vinayak Botla thanks the University Grant Commission (UGC),
New Delhi for the award of Senior Research Fellowship (SRF).
We thank Dr. B. Sridhar for his support in X-ray crystallography
analysis.
(g) S. Liang and G. Manolikakes, Adv. Synth. Catal. 2016, 358
2371; (h) M. Sun, S. Sun, H. Qiao, F. Yang, Y. Zhu, J. Kang, Y.
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8 | J. Name., 2012, 00, 1-3
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W. Y. Yu, W. N. Sit, Z. Zhou and A. S. C. Chan, Org. Lett., 2009,
11, 3174.
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Iron (III)-catalyzed chelation assisted remote C-H bond oxygenation of 8-
amidoquinolines.
Botla Vinayak, Pilli NavyaSree and Malapaka Chandrasekharam*
I&PC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
We have developed a simple, efficient oxygenation of C-H bonds that are geometrically
inaccessible in 8-amidoquinolines with inexpensive and nontoxic iron (III) catalyst. The chelation
assisted remote benzoxylation protocol tolerates wide substrate scope and is operationally simple.