Uncatalyzed, on water oxygenative cleavage of inert C-N bond with concomitant 8,7-amino shift in 8-aminoquinoline derivatives

Article abstract of DOI:10.1039/c9gc00289h

Oxygenative cleavage of an inert C_Ar-NH₂ bond with concomitant 1,2 amine migration in 8-aminoquinoline derivatives is reported in water at room temperature. The reaction is highly atom- and step-economical as both C- and N-containing fragments of the C-N bond cleavage are incorporated into the target molecule and is effected without the need for N-oxide. The reaction is scalable to gram level, and the products are useful as electrophilic partners for coupling reactions, ligands in catalysis and bioactive compounds.

Full text of DOI:10.1039/c9gc00289h

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DOI: 10.1039/C9GC00289H
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ARTICLE
Uncatalyzed, on water oxygenative cleavage of inert C-N bond with
concomitant 8, 7-amino shift in 8-aminoquinoline derivatives†
Received 00th January 20xx,
Accepted 00th January 20xx
Botla Vinayak,1 Pilli NavyaSree1, 2 and Malapaka Chandrasekharam1, 2
*
DOI: 10.1039/x0xx00000x
Oxygenative cleavage of inert CAr-NH2 bond with concomitant 1, 2 amine migration in 8-aminoquinoline derivatives is
reported in water at room temperature. The reaction is highly atom- and step-economical as both C- and N-containing
fragments of the C-N bond cleavage are incorporated into the target molecule and is effected without the need for N-oxide.
The reaction is scalable to gram level and the products are useful as electrophilic partners for coupling reactions, ligands in
catalysis and bioactive compounds.
www.rsc.org/
Chang4 also studied C-H aminations extensively.5 The amide
radical mediated direct aromatic ring amination by aqueous
ammonia with platinum loaded TiO2 catalyst is known to
Introduction,
The abundant sources of C-N bond and the facile metalation of
the inert C-N bond into more active C-M or N-M species via
transition metal catalysis has attracted tremendous attention
among chemists.1 In the absence of transition metal catalysts,
C-N bond could be cleaved and transformed through radical and
cationic intermediates. The cleavage of C-N bond of a primary
amine (R-NH2) is the most challenging task as NH2 is a poor
leaving group and hence require highly reactive cationic
intermediates such as diazonium/ammonium salts in which the
elimination of electronically neutral di nitrogen and amine
moiety facilitates the C-N bond cleavage process.2
produce less than 10% yields.6
Transposition and migration of functional groups are effective
tools in organic chemistry to achieve the synthesis of difficult
targets in a single step reaction.7,8 1,2-Amino shift was reported
in a rare biotransformation of amino acids under complex
enzyme catalysis by the cooperative action of aminomutases,
coenzyme B-12, and vitamin B-6.9a,b A Cu(I) catalysed 1,3-amino
migration via a highly reactive ketenimine intermediate was
also achieved by Talukdar etal., in the formation of
acrylamidines9c and more recently, Guan and co-workers
reported copper catalyzed oxidative cyclization/1,2-amino
migration via aziridinium intermediate for the synthesis of
substituted pyrroles,9d however, to our knowledge amino
migration in aromatic systems is unprecedented.
Figure 1. Synthesis of 7-aminoquinolin-8-ol.
Previous Work17
.
Given the importance and versatility of quinoline derivatives as
bioactive natural products, pharmaceuticals, agrochemicals,
functional materials, directing group for C-H functionalizations
and ligands in transition metal catalysis, the development of
efficient and environmentally benign methods for the
functionalisation of quinolines is highly warranted. Particularly,
7-substituted 8-hydroxy quinoline (8HQ) derivatives inhibit a
2OG oxygenase, the prolyl hydroxylase containing protein10a,b
and 7-N,N-dimethylamino quinoline derivatives are known as
small molecule fluorescent probes for applications in live cell
imaging etc.10c Due to the innate reactivity of C=N bond or the
N-adjacent C-H bond, C2 functionalizations of quinolines have
been extensively investigated and C8-functionalizations are
comparatively less studied.11a Recently Sharma etal., reported
efficient Rh-catalysed C8-alkenylation and -hydroxy alkylation
N
N
NH2
OH
OH
This Work
i) Benzoyl Peroxide
H2O
ii) Ester hydrolysis
N
N
NH2
NH2
OH
Tedious nitration-hydrogenation sequence is the traditional
choice to access aryl amines directly until the invention of
Buchwarld-Hartwig amination of aromatic halides with
ammonia.3 Other groups including Ullman, Chan-Evans-Lam,
1P&FM Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad-
500007, India. 2Academy of Scientific and Innovative Research (AcSIR),
NewDelhi110025, India. E-mail: csmalapaka@iict.res.in
†Communication number IICT/Pubs/2019/001.
Electronic Supplementary Information (ESI) available: All optimization tables, Copies
of crystallographic data (CCDC 1559199) see. See DOI: 10.1039/x0xx00000x
c
of quinoline N-oxides.11b, Cui and Wu groups investigated
decarboxylative C8-acylation of quinoline N-oxides with α-
oxocarboxylic acid.11d Noteworthy are Ru-catalysed
alkenylations reported by Shibata and Rh- and Ir-catalysed
iodination and amidation by Chang respectively.12 In metal
This journal is © The Royal Society of Chemistry 20xx
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catalysed C8-functionalizations, the oxygen of quinoline N- a new chemistry differentiating from conventiVoienwaAlrtioclregOannlinice
DOI: 10.1039/C9GC00289H
oxide serves as an exocyclic directing group via formation of a syntheses.
five membered metallacycle.13a,b Further, several reports have
been published on Pd-catalysed C2 functionalisation, only one
Results and discussion,
report describes the Pd-catalyzed selective C8-arylation of
quinoline N-oxides.13c
However, these procedures are
The mechanistic investigations of the chelation assisted, remote
C5-benzoxylation of 8-amidoquinoline with benzoyl peroxide
previously reported from our group, revealed that 8-
aminoquinoline is resistant to 5-oxygenation under the
standard reaction conditions.16e Realizing the importance of 8
substituted quinolines, we further probed the benzoxylation
reaction of 8-aminoquinoline and the new compound obtained,
to our perplexity, was 7-amino, 8-benzyloxy quinoline with an
intramolecular hydrogen bonding between the amino nitrogen
donor and electronegative carbonyl oxygen acceptor.
Apparently not only the benzoxylation occurred at 8-position
but also triggered a serendipitous encounter of 8-7 amino shift
involving multiple bond breaking (C-N, C-H) and formation (C-O
and C-N) reactions in one pot.
associated with limitations such as high temperature
conditions, use of expensive rare metal catalysts, necessitate
initial installation and later reduction of the N-O bond affecting
overall efficiency of the reaction and thus reduce the synthetic
utility. Therefore, C8-functionalisation of unmodified quinolines
represents a practical, efficient and step economic method for
the generation of important quinoline derivatives. In this
context, the only reports available in literature, to the best of
our knowledge are published by Chang and Sawamura.14 While
Chang’s pioneering work represents the first selective C8-
arylation of quinolines, catalysed by Rh(NHC) system in
presence of a strong base, Sawamura reported, a selective C8-
borylation of quinolines using a heterogeneous Ir-catalyst
system based on a silica supported cage type monophosphane
ligand SMAP, as a gateway for the construction of a variety of 8-
substituted quinolines. Though the C-8 and C-7 direct
functionalizations are scarce, C5 functionalizations of 8-
aminoquinoline derivatives for the formation of C-X (X= C, N, O,
S, P and halo) bonds are extensively investigated.15 In
continuation of our interest on C-H functionalization reactions
for the construction of C-C, C-X (X=O, N, Halogen) bonds, and
Table 1. Optimization of reaction conditionsa
O
catalyst
O
Ph
Ph
O
N
NH2
O
N
H
solvent, temp
O
O
NH2
1
2
3a
Ph
particularly
the
regioselective
introduction
of
Entry
Catalyst
Temp (°C)
Yield [%]b
aryls/heteroatoms on THQ/quinoline framework,16 we herein
report our serendipitous invention of an efficient, catalyst free,
one step synthesis of 8-benzyloxy, 7-aminoquinoline directly
from 8-aminoquinoline in water under extremely mild
conditions. The 8-amino group serves as a function as well as
functionality, particularly as traceless and migrating directing
group. The herculean tasks carried out by the benzoxylation
reaction include: 1. selective cleavage of inert CAr-N bond in
presence of C-H, C-O and C-halogen bonds, 2. amine as traceless
directing group for benzoxylation (CAr-N to CAr-O bond
formation), 3. amine migration from C8 to C7, 4. C7-H
amination. Interestingly the multiple chemical events such as
bond breaking (C-N, C-H), new bonds formation (C-O, C-N) and
group migration (-NH2) occur in the most efficient i.e., open air,
room temperature, metal- or catalyst-free, in water as the
solvent with high degree of atom- and step-economy. Both the
C- and N-fragments arising from C-N bond cleavage are
incorporated into the target molecule and the reaction
proceeds without the necessity to employ quinoline N-oxide.
Further the aqueous, ambient and open to air conditions qualify
the reaction for green technology.
1
2
3
4
5c
6
7
8
9
10
11c
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3 .6H2O
FeCl3
90
reflux
60
rt
0
rt
rt
rt
rt
rt
48
39
56
61
18
58
28
36
43
67
69
FeBr3
Fe(OTf)3
Fe(acac)3
-
-
rt
aReagents and conditions: Unless otherwise specified, a mixture of 1 (1.0 mmol)
and 2 (1.2 mmol) in water (3.0 mL) was stirred at rt for 16 h in open air. bIsolated
yield. cPortion-wise addition of BPO.
In order to optimize the reaction conditions, we began our
study with 8-aminoquinoline (1a) as a model substrate. Stirring
a solution of 1a, iron (III) chloride and benzoyl peroxide (BPO) in
a toluene solution at 90 °C resulted in formation of the product
3a in 48% yield (Table 1, entry 1). Elevation of the temperature
to reflux (110 °C) did not accelerate the course of the reaction,
rather decreased product yields (39%) accompanied with the
formation of capricious complex mixtures and benzoic acid
(Table 1, entry 2) was observed. The product yield improved to
56% when the reaction was conducted at 60 °C (Table 1, entry
3). At ambient temperature, the yield of the product was further
improved to 61% (Table 1, entry 4), whereas at 0 °C the yields
of 3a diminished to 48% despite of prolonged reaction times
(Table 1, entry 5). In the presence of other iron salts the results
were not satisfactory (Table 1, entry 6-9), while copper and
This is the first report on 1,2-amino shift on aryls via oxygenative
inert C-N bond cleavage and demonstrates a simultaneous CAr-
N oxygenation and CAr-H amination that represents an easy
entry to 7-amino-8-hydroxy quinoline derivatives.17 The
reaction represents a powerful, straightforward, practical,
atom- and step-economic strategy for constructing an
otherwise difficult to obtain new organic compounds, following
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palladium salts inhibited the reaction.18 Interestingly, significant 3k, 3l). Further, the reaction proceeded with heteroaryl acyl
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improvement of the product yield was observed in the absence peroxides as well affording the productDsOinI: 1g0o.1o0d39y/Cie9lGdCs0(0F2ig892H,
of any catalyst. However the best yield was obtained under 3n, 3o).
metal free conditions with water as a green and universal 8-Aminoquinoline was subjected to transition metal free
solvent medium at room temperature. Presumably the oxygenation-amino migration reaction with mixed peroxide
hydrogen bonding between water and nitrogen present under standard reaction conditions employing aryl-alkyl acyl
substrate facilitate faster reaction resulting in better yields peroxides i.e., benzyl acetyl- and benzyl t-butyl peroxides. In
compared to ACN and THF. 18 BPO was added to the reaction both the cases the products obtained were found to be
mixture in portionwise (1.2 mmol, 2×0.6 equiv/0.5 h). Among corresponding to the arylacyl 8-oxygenated 7-amino product 3a
the choice of benzoxylation sources, BPO was found to be the in 38% yield while the formation of the alkyl acyloxy product
most effective.18 1,10-Phenanthroline, 4,4’-bipyridine, 2,2’- was not observed.18 Acetyl peroxide and TBHP failed to afford
bipyridine, Proline did not affect the reaction indicating the the expected oxygenated product under standard reaction
absence of additive effect.18 The effect of co-oxidant and other conditions.18
reaction conditions were also investigated.18 Finally stirring a
solution of 1a and BPO (portionwise addition) at room
temperature in H2O for 16 h in open air was found to be
optimum.
Figure 3. Quinoline substrate scope for migration reaction. a
O
O
Ph
Ph
O
2a
O
N
NH2
O
N
H
H2O
O
NH2
rt, open air
1a-g
4a-g
Figure 2. Acyl peroxide substrate scope of migration reaction.a
Ph
O
O
H2O
R
Ph
O
O
R
R
O
N
NH2
O
O
N
H
rt, open air
O
O
NH2
1
2a-p
3a-p
N
NH2
O
N
NH2
N
NH2
N
NH2
O
R
O
O
O
O
O
O
Ph
4d-g
Ph
Ph
Ph
4c 78%
4a 62%
4b 75%
R = H, 3a 69%
R = 4-F, 3g 74%
R = 2-Br, 3h 66%
R = 4-Br, 3i 68%
R = 4-I, 3j 61%
R = 2-Me, 3b 75%
R = 3-Me, 3c 76%
R = 4-Me, 3d 80%
R =3,5-dimethyl 3e 78% R = 4-Ph, 3k 71%
R = 4-OMe, 3f 80% R = 4-NO2, 3m <1%
N
NH2
O
R =Cl, 4d 60% R =I, 4e54%
R=Ts,4f 62% R=NO2,4g<1
O
%
a
The reaction was performed with 1 (1.0 equiv.) and 2 (1.2 equiv, 2×0.6
equiv/0.5 h) in H2O (3 mL) at the room temperature for 16 h. under an open
air atmosphere. All reported yields are isolated yields.
R
We also subjected the electrophilic partner (phenyl boronic
acid) and electron rich substrates (β-napthol, benzimidazole
and indole) for the migration reaction with 8-aminoquinoline
under standard reaction conditions and failed to achieve C-C
bond forming reaction products at 8 position.18
N
NH2
O
N
NH2
O
N
NH2
O
N
NH2
O
O
O
O
O
S
S
3p <1%
3l 68%
3n 77%
The electronically differentiated substrate scope for quinoline
variation was also investigated. The e-donating groups i.e.,
methyl and methoxy substituents present on quinoline
influence the migration reaction and produced good yields of
the products (Fig 3, 4a-c). C6-Methoxy, 8-amino quinoline
substrate provided a challenging contiguously trisubstituted
quinoline 4c in 78% yield. It is interesting to note that good
leaving groups (Cl, I, Ts) are unaffected and selective
oxygenative cleavage of inert C-N bond occurs to deliver the
corresponding 8-benzoxylated and 8,7 amino shift products
with moderate yields (Fig 3, 4d-f). Further 5-halo/tosyl groups
serve as good handles and potential points of departure for
introducing new functionalities. However the strong electron
withdrawing nitro group at 5-position of quinolone ring (4g)
inhibited the 8-oxygenation reaction. The 5, 7-substitutions on
quinolones 5a and 5b are detrimental for the benzoxylation
reaction probably due to steric crowding. The –NH2 group at 3-
(heterocyclic ring) 5c or 6-position (carbocyclic ring) 5d are
3o 79%
a
The reaction was performed with 1 (1.0 equiv.) and 2 (1.2 equiv, 2×0.6
equiv/0.5 h) in H2O (3 mL) at the room temperature for 16 h. under an open
air atmosphere. All reported yields are isolated yields.
With the optimized conditions in hand, the substrate scope of
the reaction was investigated (Fig 2). We examined various e-
withdrawing, -donating and -neutral substituted benzoyl
peroxides as oxygenating reagents. Good yields of the C8-
oxygenated products were often achieved when unsubstituted
and electron-donating moieties including methyl and methoxy
groups were present on the aryl ring of the BPO (Fig 2, 3a-3f).
The C8-oxygenation reaction tolerated halogen substituents on
benzoyl peroxide and produced moderate yields of the products
(Fig 2, 3g−3j). Biphenyl and naphthyl peroxides also underwent
smooth reaction affording
a moderate yield of the
corresponding 8-oxygenated, 8-7 amino shift products (Fig 2,
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unaffected, indicating the importance of the 8-amino group as
efficient traceless directing as well as migrating group (Fig 4).
The amine group containing substrates 5e-g, quinoline and
other 8-hydroxy, 8-NO2, 8-halo quinolines are unreactive
towards the benzoxylation reaction.
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DOI: 10.1039/C9GC00289H
Figure 6. Mechanistic Insights.
BPO (1.2 equiv)
H2O, rt
N
O
N
NH2
O
NH2
O
O
<1%
Ph
In order to explore the migrating ability, different functionalities
on the migrating nitrogen have been evaluated. Amide,
sulfonamide (Ms, Ts, Tf), carbamate (Boc, MeOCO), secondary
amines with methyl and benzyl substituents (methylamine,
benzylamine) and tertiary amine (dimethylamine) as migrating
groups are resistant to benzoxylation reaction.18 Further we
tested the reaction in the presence of external alkyl/aryl 1°-
amines presuming to obtain 7-alkyl/aryl amino 8-benzoxylated
products under the standard reaction conditions, instead the
product 3a was obtained in 60% yield (Fig 5).
BPO (1.2 equiv)
N
N
N
NH2
O
TEMPO (2.0 equiv)
H2O, rt
NH2
1a
O
3a
58%
61%
Ph
BPO (1.2 equiv)
1,1 Diphenylethylene
(2.0 equiv)
N
NH2
O
NH2
1a
O
H2O, rt
3a
Ph
Under the standard reaction conditions, 8-aminoquonoline N-
oxide failed to afford the corresponding migration product,
ruling out the formation of N-oxide intermediate.18 Radical
clock experiments conducted in the presence of TEMPO and
1,1-diphenyl ethylene produced comparable product yields of
58% and 61% respectively indicating that the reaction does not
proceed through radical pathway (Fig 6). Further, the resistance
of the reaction with the substrates 5a-5k (Fig 4) and also failure
to incorporate external amines at 7 position (Fig. 5) suggest that
unmodified quinoline nitrogen, free amine at C8 and free C7-H
in the substrate are essential for the successes of the
oxygenative migration reaction.
Figure 4. Substrates Resistant to Migration Reaction.
Cl
Br
H2N
NH2
N
N
N
Cl
N
Br
NH2
NH2
5c
5d
5b
5a
5h, R = H
5i, R = OH
5j, R = NO2
5k, R = Br
N
N
NH2
N
All
the
NH2
R
NH2
5e
5f
5g
1
new compounds have been fully characterized using H-NMR,
13C-NMR, HRMS. Further the structure of the oxygenated
product 3d was unambiguously confirmed by single crystal X-
ray analysis.18
Figure 7. Proposed Mechanism.
-PhCO2H
3a
H
Figure 5. External N-alkyl/aryl amine source.
N
N
O
N
NH
NH
O
O
H2N
Ph
O
O
O
Ph
O
Ph
B
Ph
A
R-NH2 (1.2 equiv)
O
R
Benzoyl Peroxide
(1.2 equiv)
N
N
O
N
H
N
O
NH2
NH2
O
O
H2O, rt
1
Ph
Ph
R = Me, Et, Ph, CH2-Ph
<1%
3a 60 %
With the support of the above studies and considering the fact
that the heteroatom in the quinoline ring has considerable
deactivating effect on the ring towards electrophilic attack and
at the same time the electron-rich nitrogen atom is the main
centre for attack by electrophiles, a tentative domino reaction
mechanism as depicted in Fig. 7 has been proposed. The
internal 8-amino nucleophile attacks the vicinal C7 forming the
tricyclic aziridine which triggers the concomitant nucleophilic
attack of the ring nitrogen on benzoyl peroxide with disruption
of the aromaticity releasing benzoic acid. The neutral species,
N-benzoyloxy tricyclic aziridine intermediate (A) further
undergoes intramolecular rearrangement of the benzyloxy
group from the ring nitrogen to C8 through a 6-membered
transition state, generating intermediate B with a new
quaternary carbon. Rearomatization facilitates the breaking of
aziridine ring and 8,7 migration of NH2. Interestingly, though the
product appears to be arising from amino migration, apparently
the mechanism involves two migrations including benzyloxy
migration from nitrogen to C8.
The efficacy of the oxygenative-amino migration reaction is
further demonstrated from the formation of hydrolyzed
product, 8-hydroxy, 7-amino quinoline directly from 8-amino
quinoline in one pot.18 This class of benzyloxy products and 7-
aminoquinolin-8-ol derivatives are known to have applications
in catalysis, materials and biology (Fig. 8).10c,17a The
benzoxylation reaction could be scaled up to 1.0 gram
demonstrating the practicality of the process.18
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shifts (δ) are reported in ppm relative to the residual solvent
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signal (δ = 7.26 ppm for 1H NMR and δ = 7D7O.I0: 1p0p.1m039fo/Cr91G3CC0N0M28R9H).
Data for 1H NMR are reported as follows: chemical shift
(multiplicity, coupling constant, number of hydrogen atoms).
Multiplicity is abbreviated as follows: s (singlet), d (doublet), t
(triplet), q (quartet), m (multiplet). Mass spectra were carried
out with a Quattro LC triple-quadrupole mass spectrometer
(Micromass, Manchester, UK). High-resolution mass spectra
were determined with a Quadrupole time-of-flight (Q-TOF)
mass spectrometer (QSTARXL, Applied Biosystems/MDS Sciex,
Foster city, USA).
Figure 8. Synthetic applications.
N
NH2
O
O
Ph
N
N
N
NH2
General procedure for the synthesis of 7-aminoquinolin-8-yl
benzoate derivatives:
O
OH
O
Ligand skelton
R
Ph
N
N
N
N
R
H
Fluorescent
skelton
The 25 mL oven dried roundbottom flask was equipped with a
magnetic stir bar and charged with charged with 8-
aminoquinoline (144 mg, 1.0 mmol) in H2O (3 mL) and benzoyl
peroxide (1.2 mmol, 2×0. 6 equiv/0.5 h), at room temperature
for 16 h. 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 3a as Pale yellow solid,
182 mg (yield 69%).
General procedure for gram-scale synthesis of compound 3a:
Following the same synthetic procedure for compound 3a, the
reaction of 8-aminoquinoline (1.0 g, 6.94 mmol) in H2O (25 mL)
and benzoyl peroxide (1.2 equiv, 2×0. 6 equiv/0.5 h), at room
temperature for 16 h, to obtain the desired product 3a (yield
65%) as pale yellow solid,
O
O
O
Ph
Various
N-subistitution
Bioactive skelton
Conclusions
The efficiency of the metal free benzoxylation reaction was
demonstrated from the inert CAr-N bond cleavage, C8-
oxyganation and 8, 7 amino shift achieved on inexpensive and
commercially available 8-aminoquinoline. These above
sequence of events occured in one-pot in the most atom
economical incorporation of C- and N-containing fragments
resulting from C-N bond cleavage into the target 7-amino, 8-
benzyloxy quinoline molecule. The product 7-amino-8-
benzyloxy quinoline formation involves multiple bond breaking
(C-N, C-H) and bond formation (C-O and C-N) reactions. A
tentative mechanism has been proposed wherein the migration
of the benzyloxy group from ring nitrogen to C8 and the amine
at C8 position, after serving as a directing group for
benzoxylation, migrates to the adjacent carbon via tricyclic
aziridine intermediate. This is the first report of the most
complicated direct conversion of CAr-N to CAr-O and 1, 2 amino
shift on aryl moiety. Metal-, catalyst-, ligand-, additive-free
open air and aqueous reaction conditions, demonstrate the
operational simplicity and green protocol of the reaction. This is
the shortest and unconventional route to prepare 7-amino, 8-
hydroxy quinoline derivatives. Further mechanistic studies are
underway.
General procedure for the synthesis of acylperoxides: 16e
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 (30 mmol) 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).
Procedure for the synthesis of 6-methoxy-8-nitroquinoline: 19
Experimental
General
To a solution of 4-methoxy-2-nitroaniline (5.09 g, 33.0 mmol,
1.0 equiv) in conc. HCl (40 mL) and conc. H3PO4 (15 mL), acrolein
(6.5 mL, 97 mmol, 2.9 equiv) was slowly added at 80 °C for 1 h.
The mixture was stirred at 95 °C for 6 h, and then cooled to 0 °C.
After neutralization with aq. NH3, the resulting powder was
filtered off and dissolved in acetone. The solvent was removed
and 6-methoxy-8 nitroquinoline was obtained as a brown solid
(4.68 g, 70% yield).
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 plate. H
NMR spectra were obtained with 300, 400 and 500 MHz
spectrometers, 13C NMR spectra were obtained with 100 and
1
Procedure for the synthesis of 6-methoxyquinolin-8-amine: 19
125 MHz spectrometers in CDCl3 at 298
tetramethylsilane and CDCl3 as the internal standard. Chemical
K
with
A mixture of 6-methoxy-8-nitroquinoline (2.82 g, 13.8 mmol, 1.0
equiv), activated charcoal (1.38 g), iron chloride (448 mg, 2.76
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Journal Name
mmol, 0.20 equiv), and hydrazine monohydrate in methanol (80 7-aminoquinolin-8-yl 4-methoxybenzoate (3f): ViPewalAerticyleeOllnolinwe
1
DOI: 10.1039/C9GC00289H
mL) was stirred at 80 °C for 12 h. The reaction mixture was solid, 235.3 mg (yield: 80%), mp: 221-223 °C. H NMR (500 MHz,
filtered through celite and the solvent was removed under CDCl3): δ = 12.08 (s, 1H), 10.90 (s, 1H), 8.80-8.77 (m, 1H), 8.12-
reduced pressure to give 8-amino-6-methoxyquinoline (2.00 g, 8.07 (m, 3H), 7.56 (d, J = 8.85 Hz, 1H), 7.35-7.30 (m, 2H), 7.06 (d,
83% yield).
J = 8.85 Hz, 2H), 3.91 (s, 3H).13C NMR (100 MHz, CDCl3): δ =
166.1, 163.1, 148.6, 147.8, 141.1, 136.1, 129.6, 125.3, 124.8,
122.6, 119.1, 117.9, 114.1, 55.5. ESI-HRMS: calcd for C17H15O3N2
= 295.10772, Found 295.10779.
General procedure for synthesis of 5-tosylquinolin-8-amine: 20
To a 50 mL schlenk tube equipped with a magnetic stir bar was
added a mixture of N-(5-tosylquinolin-8-yl)benzamide (8.0
mmol), NaOH (1.0 g, 25 mmol), and EtOH (25.0 mL). Upon
completion of the reaction at 90°C for 12 h, the mixture was
cooled to room temperature and then diluted with EtOAc (50
mL). The collected organic layer was washed with brine (100
mL), dried with Na2SO4, and filtered through a pad of celite the
solvent was removed in vacuo by rotary evaporation, and
isolated by silica-gel column chromatography, desired product
(1.8 g, 83% yield).
7-aminoquinolin-8-yl benzoate (3a): Pale yellow solid, 182.2
mg (yield: 69%), mp: 101-103 °C. 1H NMR (500 MHz, CDCl3): δ =
11.95 (s, 1H), 10.47 (s, 1H), 8.80-8.75 (m, 1H), 8.13-8.08 (m, 3H),
7.65-7.60 (m, 1H), 7.59-7.54 (m, 3H), 7.34-7.30 (m, 2H).13C NMR
(125 MHz, CDCl3): δ = 166.5, 148.7, 147.7, 141.1, 136. 1, 133.1,
132.5, 128.9, 127.6, 125.1, 122.6, 119.1, 117.6. ESI-HRMS: calcd
for C16H13O2N2 = 265.09715, Found 265.09705.
7-aminoquinolin-8-yl 2-methylbenzoate (3b): Pale yellow solid,
208.6 mg (yield: 75%), mp: 97-99 °C. 1H NMR (500 MHz, CDCl3):
δ = 11.79 (s, 1H), 10.44 (s, 1H), 8.73-8.69 (m, 1H), 8.13-8.07 (m,
1H), 7.76 (d, J = 7.62 Hz, 1H), 7.58 (d, J = 9.00 Hz, 1H), 7.47-7.42
(m, 1H), 7.36-7.28 (m, 4H), 2.63 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ = 169.5, 148.7, 147.8, 140.9, 137.1, 136.0, 134.6,
131.5, 130.9, 127.6, 126.1, 125.2, 122.6, 119.1, 117.9, 20.3. ESI-
HRMS: calcd for C17H15O2N2 = 279.11280, Found 279.11414.
7-aminoquinolin-8-yl 3-methylbenzoate (3c): Pale yellow solid,
211.4 mg (yield: 76%), mp: 86-88 °C. 1H NMR (400 MHz, CDCl3):
δ = 11.96 (s, 1H), 10.92 (s, 1H), 8.79-8.75 (m, 1H), 8.10-8.06 (m,
1H), 7.91-7.87 (m, 2H), 7.55 (d, J = 9.04 Hz, 1H), 7.46 -7.42 (m,
2H), 7.33-7.29 (m, 2H), 2.47 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ = 166.6, 148.6, 147.8, 141.0, 138.8, 135.9, 133.2, 128.7, 128.3,
124.9, 124.4, 122.5, 121.5, 119.0, 117.6, 21.36. ESI-HRMS: calcd
for C17H15O2N2 = 279.11280, Found 279.11415.
7-aminoquinolin-8-yl 4-fluorobenzoate (3g): Pale yellow solid,
208.7 mg (yield: 74%), mp: 109-111 °C. H NMR (500 MHz,
1
CDCl3): δ = 11.84 (s, 1H), 10.93 (s, 1H), 8.78-8.77 (m, 1H), 8.14-
8.10 (m, 3H), 7.57 (d, J = 9.00 Hz, 1H), 7.34-7.31 (m, 2H), 7.26-
7.23 (m, 2H).13C NMR (100 MHz, CDCl3): δ = 166.6, 165.3, 164.1.
148.7, 147.8, 141.0, 136.1, (130.1-130.0 d) 129.2, 125.1, 122.6,
119.1, 117.5, 116.1, 115.9. ESI-HRMS: calcd for C16H12O2N2F =
283.08773, Found 283.08735.
7-aminoquinolin-8-yl 2-bromobenzoate (3h): Pale yellow solid,
225.7 mg (yield: 66%), mp: 155-157 °C. 1H NMR (400 MHz,
CDCl3): δ = 11.48 (s, 1H), 10.58 (s, 1H), 8.73-8.69 (m, 1H), 8.12-
8.07 (m, 1H), 7.79-7.72 (m, 2H), 7.60 (d, J = 9.04 Hz, 1H), 7.50-
7.46 (m, 1H), 7.43-7.39 (m, 1H), 7.35-7.29 (m, 2H).13C NMR (100
MHz, CDCl3): δ = 167.1, 148.7, 147.8, 140.9, 136. 5, 136.1, 133.9,
132.0, 129.7, 127.6, 125.5, 122.5, 119.9, 119.2, 117.5. ESI-
HRMS: calcd for C16H12O2N2Br = 343.00767, Found 343.00978.
7-aminoquinolin-8-yl 4-bromobenzoate (3i): Pale yellow solid,
232.5 mg (yield: 68%), mp: 178-180 °C. 1H NMR (500 MHz,
CDCl3): δ = 11.78 (s, 1H), 10.96 (s, 1H), 8.80-8.77 (m, 1H), 8.13-
8.10 (m, 1H), 7.98 (d, J = 8.54 Hz, 2H), 7.71 (d, J = 8.54 Hz, 2H),
7.58 (d, J = 9.00 Hz, 1H), 7.35-7.32 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ = 165.5, 148.7, 147.9, 141.0, 136.1, 132.2, 129.2,
127.4, 125.3, 122.6, 119.2, 117.4. ESI-HRMS: calcd for
C16H12O2N2Br = 343.0077, Found 343.0077.
7-aminoquinolin-8-yl 4-iodobenzoate (3j): Pale yellow solid,
238.5 mg (yield: 61%), mp: 141-143 °C. 1H NMR (500 MHz,
CDCl3): δ = 12.08 (s, 1H), 10.98 (s, 1H), 8.76-8.72 (m, 1H), 8.31-
8.26 (m, 1H), 8.11-8.09 (m, 2H), 7.94-7.91 (m, 1H), 7.65-7.62 (m,
1H), 7.59-7.56 (m, 2H), 7.41-7.37(m, 1H). 13C NMR (100 MHz,
CDCl3): δ = 166.6, 149.2, 148.1, 140.5, 133.3, 132.7, 128.9,
127.6, 124.4, 120.5, 118.5, 93.5. ESI-HRMS: calcd for
C16H12O2N2I = 390.99380, Found 390.99403.
7-aminoquinolin-8-yl [1,1'-biphenyl]-4-carboxylate (3k): Pale
yellow solid, 241.5 mg (yield: 71%), mp: > 250 °C. 1H NMR (400
MHz, CDCl3): δ = 11.99 (s, 1H), 11.04 (s, 1H), 8.82-8.79 (m, 1H),
8.20 (d, J = 8.43 Hz, 2H), 8.14-8.10 (m, 1H) 7.80 (d, J = 8.55 Hz,
2H), 7.69-7.66 (m, 2H), 7.58 (d, J = 9.04 Hz, 1H), 7.52-7.48 (m,
2H), 7.45-7.40 (m, 1H), 7.36-7.32 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ = 166.3, 148.7, 147.9, 145.3, 141.2, 139.8, 136.2,
131.8, 128.9, 128.2, 127.6, 127.3, 125.1, 122.7, 119.2, 117.8.
ESI-HRMS: calcd for C22H17O2N2 = 341.12845, Found 341.12846.
7-aminoquinolin-8-yl 2-naphthoate (3l): Pale yellow solid,
213.6 mg (yield: 68%), mp: 210-212 °C. 1H NMR (500 MHz,
CDCl3): δ = 12.02 (s, 1H), 11.10 (s, 1H), 8.81-8.79 (m, 1H), 8.62
(s, 1H), 8.12-8.08 (m, 2H), 8.04-7.98 (m, 2H), 7.92-7.89 (m, 1H),
7.62-7.54 (m, 3H), 7.35-7.30 (m, 2H). 13C NMR (100 MHz, CDCl3):
δ = 166.4, 148.7, 147.8, 141.1, 136.1, 135.1, 132.5, 130.1, 129.2,
128.8, 128.2, 127.7, 126.1, 125.1, 123.4, 122.6, 119.1, 117.7.
ESI-HRMS: calcd for C20H15O2N2 = 315.11280, Found 315.11459.
7-aminoquinolin-8-yl 4-methylbenzoate (3d): Pale yellow solid,
224.5 mg (yield: 80%), mp: 148-150 °C. H NMR (400 MHz,
1
CDCl3): δ = 12.02 (s, 1H), 10.93 (s, 1H), 8.79-8.71 (m, 1H), 8.11-
8.08 (m, 1H), 8.01 (d, J = 8.19 Hz, 2H), 7.57-7.54 (m,1H), 7.36 (d,
J = 7.94 Hz, 2H), 7.34-7.30 (m, 2H), 2.46 (s, 3H).13C NMR (125
MHz, CDCl3): δ = 166.4, 148.6, 147.7, 143.2, 140.9, 135.9, 130.1,
129.5, 127.5, 124.9, 122.5, 119.0, 117.7, 21.5. ESI-HRMS: calcd
for C17H14O2N2 = 279.1151, Found 279.1149.
7-aminoquinolin-8-yl 3,5-dimethylbenzoate (3e): Pale yellow
solid, 227.8 mg (yield: 78%), mp: 143-145 °C. 1H NMR (400 MHz,
CDCl3): δ = 11.96 (s, 1H), 10.87 (s, 1H), 8.81-8.77 (m, 1H), 8.12-
8.07 (m, 1H), 7.72-7.67 (m,1H), 7.56 (d, J = 9.04 Hz, 2H), 7.35-
7.29 (m, 2H), 7.26-7.23 (m,1H), 2.44 (s, 6H).13C NMR (100 MHz,
CDCl3): δ = 167.0, 148.7, 147.8, 138.6, 136.1, 134.1, 133.1,125.3,
125.0, 122.63, 119.1, 117.8, 21.3. ESI-HRMS: calcd for
C18H17O2N2 = 293.12845, Found 293.12993.
6 | J. Name., 2012, 00, 1-3
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7-aminoquinolin-8-yl thiophene-3-carboxylate (3n): Pale 7-amino-5-tosylquinolin-8-yl benzoate (4f): PaleVyieewllAortwiclesOonlliidne,
1
1
DOI: 10.1039/C9GC00289H
yellow solid, 207.9 mg (yield: 77%), mp: 185-187 °C. H NMR 259.2 mg (yield: 62%), mp: 235-237 °C. H NMR (400 MHz,
(400 MHz, CDCl3): δ = 11.68 (s, 1H), 10.86 (s, 1H), 8.80-8.75 (m, CDCl3): δ = 12.12 (s, 1H), 11.19 (s, 1H), 9.04-9.01 (m, 1H), 8.83-
1H), 8.12-8.08 (m, 1H), 7.92-7.90 (m, 1H), 7.68-7.62 (m, 1H), 8.79 (m, 1H), 8.25-8.23 (m, 1H), 8.12-8.09 (m, 2H), 7.86 (d, J =
7.57-7.54 (m, 1H), 7.34-7.30 (m, 2H) 7.23-7.20 (m, 1H). 13C NMR 8.43 Hz, 2H), 7.67-7.64 (m, 1H), 7.61-7.58 (m, 2H), 7.51-7.49 (m,
(100 MHz, CDCl3): δ = 161.1, 148.6, 147.5, 140.7, 137.6, 136.1, 1H), 7.45-7.41 (m, 1H), 7.29 (d, J = 7.94 Hz, 1H), 2.38 (s, 3H). 13
131.9, 129.7, 128.1, 124.9, 122.5, 119.1, 117.3. ESI-HRMS: calcd NMR (125 MHz, CDCl3): δ = 167.1, 149.1, 146.0, 144.4, 140.9,
for C14H11O2N2S = 271.05357, Found. 271.05486. 138.2, 133.6, 133.1, 132.4, 129.9, 129.0, 128.4, 127.7, 127.5,
C
7-aminoquinolin-8-yl benzo[b]thiophene-2-carboxylate (3o): 126.3, 122.5, 120.6, 118.5, 21.5. ESI-HRMS: calcd for
1
Pale yellow solid, 252.8 mg (yield: 79%), mp: 193-195 °C. H C23H19O4N2S = 419.10600, Found 419.10891.
NMR (400 MHz, CDCl3): δ = 11.62 (s, 1H), 11.02 (s, 1H), 8.86-8.82
(m, 1H), 7.98-7.92 (m, 2H), 7.59 (d, J = 8.92 Hz, 1H), 7.51-7.45
(m, 2H), 7.32-7.30 (m, 2H). 13C NMR (100 MHz, CDCl3): δ = 161.6,
148.8, 147.8, 141.6, 140.9, 139.0, 137.1, 136.2, 127.0, 126.9,
125.4, 125.3, 125.2, 122.8, 122.7, 122.6, 119.28, 117.4.
7-amino-2-methylquinolin-8-yl benzoate (4a): Pale yellow
solid, 172.4 mg (yield: 62%), mp: 140-142 °C. 1H NMR (500 MHz,
CDCl3): δ = 11.94 (s, 1H), 11.06 (s, 1H), 8.12-8.09 (m, 2H), 7.95
(d, J = 8.24 Hz, 1H), 7.64-7.60 (m, 1H), 7.59 -7.55 (m, 2H), 7.48
(d, J = 8.85 Hz, 1H), 7.25-7.23 (m, 1H), 7.17 (d, J = 8.24 Hz, 1H)
2.72 (s, 3H). 13C NMR (125 MHz, CDCl3): δ = 166.0, 1, 157.6,
147.7, 140.4, 136.1, 133.2, 132.4, 128.9, 128.3, 127. 5, 124.7,
121.2, 120.5, 119.7, 117.1, 25.3.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Vinayak Botla thanks the University Grant Commission (UGC),
New Delhi for the award of Senior Research Fellowship (SRF).
We thank Dr. B. V Rao, Dr. S. Raghavan for discussions and Dr.
B. Sridhar for his support in X-ray crystallography analysis.
7-amino-6-methylquinoline-5,8-diyl dibenzoate (4b): Pale
1
yellow solid, 208.6 mg (yield: 75%), mp: 212-214 °C. H NMR
Notes and references
(400 MHz, CDCl3+CD2Cl2): δ = 12.28 (s, 1H), 10.90 (s, 1H), 8.78-
8.73 (m, 1H), 8.38-8.30 (m, 2H), 8.15-8.11 (m, 2H), 8.05-8.01 (m,
1H), 7.76-7.69 (m, 1H), 7.64-7.55 (m, 5H) 7.31-7.27 (m, 1H), 2.35
(s, 3H). 13C NMR (100 MHz, CDCl3): δ = 166.6, 164.56, 148.3,
147.6, 141.6, 139.4, 134.1, 133.1, 132.5, 130.4, 130.16, 128.9,
128.83, 128.60, 127.7, 123.8, 119.3, 116.9, 116.0, 10.86. ESI-
HRMS: calcd for C24H19O4N2 = 399.13393, Found. 399.13677.
7-amino-6-methoxyquinolin-8-yl benzoate (4c): Pale yellow
solid, 229.4 mg (yield: 78%), mp: 220-222 °C. 1H NMR (400 MHz,
CDCl3): δ = 12.34 (s, 1H), 10.97 (s, 1H), 8.69-8.64 (m, 1H), 8.15-
8.10 (m, 2H), 8.04-8.00 (m, 1H), 7.64-7.56 (m, 3H), 7.34-7.28 (m,
1H) 6.96-6.90 (m, 1H), 4.04 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ = 166.7, 151.5, 146.1, 140.6, 137.1, 134.5, 132.6, 130.4, 129.9,
128.9, 127.7, 122.9, 119.7, 118.1, 101.7, 56.1. ESI-HRMS: calcd
for C17H15O3N2 = 295.10772, Found. 295.10948.
7-amino-5-chloroquinolin-8-yl benzoate (4d): Pale yellow solid,
178.8 mg (yield: 60%), mp: 151-153 °C. 1H NMR (400 MHz,
CDCl3): δ = 12.14 (s, 1H), 10.93 (s, 1H), 8.89-8.81 (m, 1H), 8.49
(d, J = 8.43 Hz, 1H), 8.11 (d, J = 7.70 Hz, 2H), 7.68-7.57 (m, 3H),
7.47-7.39 (m, 2H). 13C NMR (100 MHz, CDCl3): δ = 166.5, 149.3,
147.6, 141.1, 133.4, 132.8, 132.7, 128.9, 127.6, 122.4, 120.6,
119.7, 117.0. ESI-HRMS: calcd for C16H12O2N2Cl = 299.05818,
Found. 299.05993.
1
(a) Z. -C. Cao, S. -J. Xie, H. Fang and Z. -J. Shi, J. Am. Chem. Soc.
2018, 140, 13575; (b) S. Ueno, N. Chatani and F. Kakiuchi, J.
Am. Chem. Soc. 2007, 129, 6098; (c) Q. Wang, Y. Su, L. Li and
H. Huang, Chem. Soc. Rev. 2016, 45, 1257.
(a) K. Ouyang, W. Hao, W. –X. Zhang and Z. Xi, Chem. Rev.
2015, 115, 12045; (b) X. Cong, F. Fan, P. Ma, M. Luo, H. Chen
and X. Zeng, J. Am. Chem. Soc. 2017, 139, 15182.
2
3
(a) A. S. Guram and S. L. Buchwald, J. Am. Chem. Soc. 1994,
116, 7901; (b) S. Shekhar, P. Ryberg and J. F. Hartwig, J. Am.
Chem. Soc. 2006, 128, 3584.
4
5
H. Kim and S. Chang, ACS Catal. 2016, 6, 2341.
(a) S. C. Cosgrove, J. M. C. Plane and S. P. Marsden, Chem. Sci.
2018, 9, 6647; (b) K. Murakami, G. J. P. Perry and K. Itam, Org.
Biomol. Chem. 2017, 15, 6071; (c) T. Xiong and Q. Zhang,
Chem. Soc. Rev. 2016, 45, 3069; (d) N. A. Romero, K. A.
Margrey, N. E. Tay and D. A. Nicewicz, Science. 2015, 349,
1326.
6
7
a) H. Yuzawa and H. Yoshida, Chem. Commun. 2010, 46, 8854;
(b) H. Yuzawa, J. Kumagai and H. Yoshida, J. Phys. Chem. C.
2013, 117, 11047.
(a) G. R. Pettit, J. W. Lippert and D. L. A. Herald, J. Org. Chem.
2000, 65, 7438; (b) X. Liu, F. Xiong, X. Huang, L. Xu, P. Li and X.
Wu, Angew. Chem. Int. Ed. 2013, 52, 6962; (c) J. Zhao, H. Fang,
R. Song, J. Zhou, J. Han and Y. Pan, Chem. Commun. 2015, 51,
599; (d) Z.-M. Chen, W. Bai, S.-H. Wang, B.-M. Yang, Y.-Q. Tu
and F. -M. Zhang, Angew. Chem. Int. Ed. 2013, 52, 9781; (e) H.
Egami, R. Shimizu, Y. Usui and M. Sodeoka, Chem. Commun.
2013, 49, 7346; (f) N. Jiang, Z. Qu and J. Wang, Org. Lett. 2001,
3, 2989.
(a) Z. He, A. Zajdlik, J. D. St. Denis, N. Assem and A. K. Yudin, J.
Am. Chem. Soc. 2012, 134, 9926; (b) T. Zhou, F. –X. Luo, M. –
Y. Yang, and Z. –J. Shi. J. Am. Chem. Soc. 2015, 137, 14586.
(a) S. D. Wetmore, D. M. Smith and L. Radom, J. Am. Chem.
Soc. 2000, 122, 10208; (b) S. D. Wetmore, D. M. Smith and L.
Radom, J. Am. Chem. Soc. 2001, 123, 8678; (c) D. P. Chauhan,
S. J. Varma, A. Vijeta, P. Banerjee and P. Talukdar, Chem.
7-amino-5-iodoquinolin-8-yl benzoate (4e): Pale yellow solid,
210.6 mg (yield: 54%), mp: 203-205 °C. 1H NMR (500 MHz,
CDCl3): δ = 12.08 (s, 1H), 10.98 (s, 1H), 8.75-8.72 (m, 1H), 8.30-
8.26 (m, 1H), 8.11-8.09 (m, 2H), 7.93 (s, 1H), 7.66-7.62 (m, 1H),
7.59-7.56 (m, 2H), 7.41-7.38 (m, 1H). 13C NMR (100 MHz, CDCl3):
δ = 166.6, 149.2, 148.0, 140.6, 140.5, 133.3, 132.7, 128.9, 127.6,
124.4, 122.5, 120.6, 118.5, 93.5. ESI-HRMS: calcd for
C16H12O2N2I = 390.99380, Found. 390.99691.
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Commun. 2014, 50, 323; (d) M. -N. Zhao, Z. –J. Zhang, Z. –H.
Journal Name
View Article Online
Ren, D. –S. Yang and Z. –H. Guan, Org. Lett. 2018, 20, 3088.
10 (a) N. A. Smirnova, I. Rakhman, N. Moroz, M. Basso, J.
Payappilly, S. Kazakov, F. Hernandez-Guzman, I. N. Gaisina, A.
P. Kozikowski, R. R. Ratan, and I. G. Gazaryan, Chem. Biol.
2010, 17, 380; (b) C. C. Thinnes, A. Tumber, C. Yapp, G.
Scozzafava, T. Yeh, M. C. Chan, T. A. Tran, K. Hsu, H.
Tarhonskaya, L. J. Walport, S. E. Wilkins, E. D. Martinez, S.
Muller, C. W. Pugh, P. J. Ratcliffe, P. E. Brennan, A. Kawamura
and C. J. Schofield, Chem. Commun. 2015, 51, 15458; (c) J. V.
Jun, E. J. Petersson and D. M. Chenoweth, J. Am. Chem. Soc.
2018, 140, 9486.
DOI: 10.1039/C9GC00289H
11 (a) T. Iwai, M. Sawamura, ACS Catal. 2015, 5, 5031; (b) R.
Sharma, R. Kumar, R. Kumar, P. Upadhyay, D. Sahal and U.
Sharma, J. Org. Chem. 2018, 83, 12702; (c) R. Sharma, R.
Kumar, I. Kumar and U. Sharma, Eur. J. Org. Chem. 2015, 7519;
(d) X. Chen, X. Cui and Y. Wu, Org. Lett. 2016, 18, 3722.
12 (a) T. Shibata and Y. Matsuo, Adv. Synth. Catal. 2014, 356,
1516; (b) J. –B. Liu, X. –H. Sheng, C. –Z. Sun, F. Huang and D.
–Z. A. Chen, ACS Catal. 2016, 6, 2452; (c) N. Barsu, M. Sen, J.
R. Premkumar and B. Sundararaju, Chem. Commun. 2016, 52,
1338.
13 (a) H. Hwang, J. Kim, J. Jeong and S. Chang, J. Am. Chem. Soc.
2014, 136, 10770; (b) D. Gwon, H. Hwang, H. K. Kim, S. R.
Marder and S. Chang, Chem. Eur. J. 2015, 21, 17200; (c) D. E.
Stephens, J. Lakey-Beitia, A. C. Atesin, T. A. Atesin, G. Chavez,
H. D. Arman and O. V. Larionov, ACS Catal. 2015, 5, 167.
14 (a) J. Kwak, M. Kim and S. Chang, J. Am. Chem. Soc. 2011, 133,
3780; (b) S. Konishi, S. Kawamorita, T. Iwai, P. G. Steel, T. B.
Marder and M. Sawamura, Chem. Asian J. 2014, 9, 434.
15 (a) X. Cong and X. Zeng, Org. Lett. 2014, 16, 3716; (b) L. Zhu,
R. Qiu, X. Cao, S. Xiao, X. Xu, C. T. Au and S. F. Yin, Org. Lett.
2015, 17, 5528; (c) S. Liang and G. Manolikakes, Adv. Synth.
Catal. 2016, 358, 2371; (d) M. Sun, S. Sun, H. Qiao, F. Yang, Y.
Zhu, J. Kang, Y. Wu and Y. Wu, Org. Chem. Front. 2016, 3,
1646; (e) Y. He, N. Zhao, L. Qiu, X. Zhang and X. Fan, Org. Lett.
2016, 18, 6054; (f) N. S. Rao, G. M. Reddy, B. Sridhar and M.
H. Sarma, Eur. J. Org. Chem. 2017, 3, 438; (g) L. K. Jin G. P. Lu
and C. Cai, Org. Chem. Front. 2016, 3, 1309.
16 (a) M. Chandrasekharam, B. Chiranjeevi, K. S. V. Gupta and B.
Sridhar, J. Org. Chem. 2011, 76, 10229; (b) B. Chiranjeevi, B.
Vinayak, T. Parsharamulu, V. S. Phanibabu, B. Jagadeesh and
M. Chandrasekharam, Eur. J. Org. Chem. 2014, 35, 7839; (c) B.
Vinayak and M. Chandrasekharam, Org. Lett. 2017, 19, 3528;
(d) B. Vinayak, A. Ashok and M. Chandrasekharam, Eur. J. Org.
Chem. 2017, 47, 7127; (e) B. Vinayak, P. Navyasree and M.
Chandrasekharam, Org. Biomol. Chem. 2017, 15, 9200; (f) B.
Vinayak, A. Ashok and M. Chandrasekharam, Tetrahedron
Lett. 2019, 60, 115.
17 (a) A. S. Hammam, A. S. Yanni, Z. H. Khalil and A. A.
Abdel-Hafez, J. Chem. Technol. Biotechnol. 1982, 32, 485; (b)
K. Matsumura, J. Am. Chem. Soc., 1927, 49, 810.
18 See supporting information for optimization tables and
supporting studies.
19 Y. Kuninobu, M. Nishi, M. Kanai, Org. Biomol. Chem., 2016, 14,
8092.
20 J. Xu, C. Shen, X. Zhu, P. Zhang, M. J. Ajitha, K. -W. Huang, Z.
An, X. Liu, Chem. Asian J. 2016, 11, 882.
8 | J. Name., 2012, 00, 1-3
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Green Chemistry
View Article Online
DOI: 10.1039/C9GC00289H
Uncatalyzed, on water oxygenative cleavage of inert C-N bond with
concomitant 8, 7-aminoshift in 8-aminoquinoline derivatives.
Botla Vinayak1, Pilli NavyaSree1, 2 and Malapaka Chandrasekharam*1, 2.
1P&FM Division, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad-500007,
India.2Academy of Scientific and Innovative Research (AcSIR), New Delhi 110025, India.
The Oxygenative cleavage of inert CAr-NH2 bond with concomitant 1, 2 amine migration
in 8-aminoquinoline derivatives is reported. An efficient, catalyst free, one step synthesis
of 8-benzyloxy, 7-aminoquinoline directly from 8-aminoquinoline in water at room
temperature under extremely mild conditions with high degree of atom- and step-
economy.
O
O
R
R
O
New C-N bond
NH2
O
H2O
N
H
N
NH2
O
O
Migration of amine
from C8 to C7
New C-O bond
Inert C-N bond
cleavage
R
C-H amination
metal/catalyst free atom & step economy H2O as green solvent
room temp, open flask