Environmentally benign synthesis of 4-aminoquinoline-2-ones using recyclable choline hydroxide

Article abstract of DOI:10.1039/c4nj01281j

Greener synthesis of 4-aminoquinoline-2-ones was achieved by intramolecular cyclization of 2-cyanophenylamide derivatives using biodegradable and recyclable choline hydroxide (ChOH). The reaction proceeds rapidly and affords the corresponding 4-aminoquinoline-2-ones with a good to excellent yield. The protocol has the advantage of easy workup, high yields, and an environmentally benign methodology compared to other reported methods. The simplicity of this method makes it an interesting alternative to other approaches.

Full text of DOI:10.1039/c4nj01281j

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: A. K. Sanap and G.
S. Shankarling, New J. Chem., 2014, DOI: 10.1039/C4NJ01281J.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/njc

Page 1 of 9
New Journal of Chemistry
View Article Online
DOI: 10.1039/C4NJ01281J
Graphical abstract
O
O
O
2
CN
2
CN
R
O
O
3
CN
NH
O
EtO
R
Cl
2
4
R
R3
1
R
N
H
1
R
N
H
o
2
0 oC - RT
DCM
1
30
C
1
R
5
a-5e
3a-3h
Xylene
1
R1 = H, F, Cl, O-Cyclohexyloxy
R2 = 7-methylcoumarin-4yl, CN, Ph, COOEt
R3 = CH
, Ph
ChOH
ChOH
3
NH
2
O
NH
2
R2
O
3
R
R1
N
H
O
1
R
N
H
6i-6m
6a-6h

New Journal of Chemistry
New Journal of Chemistry
Page 2 of 9
Dynamic Article Links ►
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
View Article Online
DOI: 10.1039/C4NJ01281J
PAPER
Environmentally benign synthesis of 4-aminoquinoline-2-ones using
recyclable choline hydroxide
Anita Kailas Sanap, and Ganapati Subray Shankarling*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Greener synthesis of 4-aminoquinoline-2-ones was achieved by intramolecular cyclization of 2-cyanophenylamide derivatives using
biodegradable and recyclable choline hydroxide (ChOH). Reaction proceeds rapidly and affords the corresponding 4-aminoquinoline-2-
ones with good to excellent yield. The protocol has the advantage of easy workup, high yield, and an environmentally benign
methodology compared to other reported methods. The simplicity of this method makes it an interesting alternative to other approaches.
1
0
Introduction
5
,6
5
5
6
6
7
7
8
8
0
5
0
5
0
5
0
5
yield of quinolone derivatives. Low yields were obtained in the
cyclisation of the malonyl ester amide of 2-aminobenzonitrile and
4
-Amino-2(1H)-quinolone scaffold can be found in a large
variety of biologically active compounds. 4-Amino-2(1H)-
quinolone derivatives have attracted attention of researchers not
only because of their strong pain-relief activity but also due to
their extremely weak acidic properties. Many non-narcotic
analgesics are strong acids; even their salts can cause ulcers.
There is no basis for such a side effect in case of 4-amino-2(1H)-
quinolone derivatives, at least, in such pronounced form. 4-
Amino-3-phenylquinolin-2(1H)-one shows antagonist activity at
2
-cyanophenyl-N-acetoacetamide
coordinating both the β-dicarbonyl moiety and the cyano group of
the same molecule, possibly due to geometric reasons. In some
cases intramolecular cyclisation of corresponding amides of 2-
due
to
difficulty
in
1
2
2
3
3
4
5
0
5
0
5
0
5
7,8
aminobenzonitriles were9 reported using sodium hydride,
10
potassium tert-butoxide, and LiHMDS.
4-Amino-2(1H)-
quinolones were synthesized from the reaction of 4-hydroxy-2-
quinolones with benzylamine and cleavage of the benzyl group
by catalytic hydrogenation. Synthesis of 4-amino-2-quinolones
were also reported using conventional amination of 4-hydroxy or
-chloro derivatives with NH3 in a sealed tube or from the
reaction of 4-hydroxyquinolones with benzyl ammonium chloride
at high temperature. Recently, Toche R. B. et al reported the
ethyl-4-amino-2-oxo-1,2-dihydroquinoline-3-
carboxylate by the reaction of 2-aminobenzonitrile with
the glycine site on the NMDA (N-methyl-D-aspartate) receptor
and anticonvulsant activity.
11
1
Additionally, 4-amino-3-
benzimidazol-2-ylhydroquinolin-2-one was reported as tyrosine
kinase receptor and their analogues are reversible ATP
competitive inhibitors of VEGFR-2, FGFR-1, and PDGFR with
IC50 values <0.1µM. Considering the significant applications
of quinolones in the field of medicinal and agrochemical, there
has been tremendous interest in developing new efficient
synthetic strategies which involves rapid functionalization and
diversification of quinolones.
12
4
13
2,3
synthesis
of
14
diethylmalonate using sodium ethoxide in long reaction times.
These methods, however, suffer from one or another
drawback, such as the use of metal mediated catalysis, more
number of steps, strong basic conditions, longer reaction times,
moisture-sensitive catalysts, or expensive reagents, and low
conversions, which limit its practical utility in organic synthesis.
Our protocol describes a simple method for the synthesis of 4-
amino-2(1H)-quinolones from its corresponding amides that were
prepared from 2-aminobenzonitriles.
Therefore, various synthetic methodologies have been
reported to access these molecules as backbone in their active
moieties. Literature survey on the synthesis of 4-amino-3-
substituted-2(1H)-quinolones did not show uniform reaction
conditions. 4-Amino-1,2-dihydro-2-oxo-3-quinolinecarbonitrile
was synthesized in five steps starting from isatoic anhydride and
dimethyl malonate to give 4-hydroxyquinolone derivative which
In recent years, the use of environmentally benign
catalysts is receiving tremendous interest in different areas of
4
on further reactions gave a title compound. Direct reaction of 2-
aminobenzonitriles with dialkyl malonates gave very low yield of
15
organic synthesis.
Choline hydroxide (ChOH) is an
5
the product. In alternative approach, the intramolecular
environmentally benign, easy to prepare base, which display
strong basicity. It has received considerable interest as an
economical, easily available, and recyclable catalyst for various
organic transformations. It was thought worthwhile to explore the
catalytic potential of ChOH for this particular conversion. In view
cyclization of malonyl ester amide of 2-aminobenzonitrile and 2-
cyanophenyl-N-acetoacetamide were reported using tin (IV)
chloride, sodium methoxide and sodium ethoxide to give low
*
Dyestuff Technology Department, Institute of Chemical
of the above and as a part of our ongoing program to develop
4
5
Technology, N. P. Marg, Matunga, Mumbai - 400019, India
Tel.: 91-22-33612708, Fax: +91-22-33611020
E-mail address: gsshankarling@gmail.com
16–22
viable protocols,
we report herein a ChOH catalyzed, mild,
simple, and efficient procedure for the construction of 4-amino-2-
quinolones.
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Page 3 of 9
New Journal of Chemistry
Experimental
corresponding amide derivatives (3a-3h) using the literature
23
55
procedure (Scheme 1).
Materials and equipments
View Article Online
O
DOI: 10.1039/C4NJ01281J
CN
O
CN
All the solvents and chemicals were procured from S D fine
chemicals (India) and were used without further purification. The
reactions were monitored by TLC using 0.25 mm E-Merck silica
gel 60 F254 precoated plates, which were visualized with UV
0
o
C - RT
R2
+
R2
Cl
NH2
DCM
R1
N
5
R1
H
1
2
3a-3h
1
light. H NMR spectrums were recorded on Bruker 400 MHz
R1 = H, F, Cl
O-cyclohexyloxy
R2
=
spectrometer, and chemical shifts are expressed in δ ppm using
TMS as an internal standard. Mass spectral data were obtained
with micromass-Q-Tof (YA105) spectrometer. Infrared spectra
were recorded on Jasco-FT/IR 4100 LE ATR PRO450-S
spectrometer.
H
3
C
O O
=
R2 = CN, Ph, CO Et
2
1
0
Scheme 1 : Synthesis of 3a-3h using 2-aminobenzoniriles and
acid chlorides
Preparation of choline hydroxide
60
N-(2-Cyanophenyl)-3-oxobutanamides (5a-5d) and N-(2-
cyanophenyl)-3-oxo-3-phenylpropanamide (5e) were prepared by
the reaction of 2-aminobenzonitriles (1) with ethylacetoacetate
and ethyl benzoylacetate in boiling xylene as per reported
1
5
To a solution of choline chloride in methanol, potassium
hydroxide was added at room temperature. Then it was heated to
o
6
1
C for 12 h with constant stirring. After cooling to room
24
temperature, the reaction mixture was filtered to remove solid
KCl and solution was obtained. This was concentrated to remove
methanol and used without further purification.
procedures (Scheme 2).
CN
O
O
CN
2
0
130 C
o
O
O
+
EtO
R3
NH
2
Xylene
N
H
R
3
General procedure for preparation of 3a-3h
R1
R1
1
4
5a-5e
To
a solution of 2-aminobenzonitrile (1) (10 mmol) in
R
1
= H, F, Cl
R3 = CH
3
, Ph
dichloromethane (15 mL), 2 (10 mmol) was added at 0 °C. The
mixture was stirred at room temperature for 1 h. After completion
of the reaction, volatile components of the reaction mixture were
removed under reduced pressure to give oil. It was quenched with
ice cold water (10 mL) and the solution was extracted with ethyl
acetate (25 mL x 3). The combined extracts were washed with
saturated NaHCO3 (2x10 mL) and dried over Na SO . After
6
5
= O-cylohexyloxy
2
5
Scheme 2: Synthesis of N-(2-cyanophenyl)-3-oxobutanamides
(5a-5d) and N-(2-cyanophenyl)-3-oxo-3-phenylpropanamide (5e)
using 2-aminobenzoniriles and β-ketoester
2
4
70
3
0
removal of the solvent, the residue was purified by
recrystallization in ethyl acetate to afford 3 as a pale yellow solid.
Optimization of reaction conditions
In order to optimize the reaction conditions for cyclization, the
effect of different organic bases and solvents were investigated in
detail for the reactions of 2-cyano-N-(2-cyanophenyl)acetamide
(3a) and N-(2-cyanophenyl)-3-oxobutanamide (5a). The outcome
is presented in Table 1. It is evident that no conversion into the
product was obtained in the absence of base even after a
prolonged reaction time of 24 h (Table 1, entry 1). Deep eutectic
mixtures (DES) such as choline chloride (ChCl): urea, ChCl:
General procedure for preparation of 5a-5e
To a solution of 2-aminobenzonitrile (1) (10 mmol) in dry xylene
7
8
8
9
9
5
0
5
0
5
(15 mL), 4 (12 mmol) was added. The reaction mixture was
3
4
4
5
0
5
refluxed for 4 h in a round-bottomed flask fitted with a Dean-
Stark apparatus, kept in an oil bath. After completion of the
reaction, it was cooled to 0 °C to let the products solidify and
filtered. The crude product was washed with diethyl ether to
afford 5 as a pale yellow solid.
malonic acid, ChCl: oxalic acid, have intrinsic advantages as
16,17
green catalysts.
Hence, attempts were made to study the
model reactions using these catalysts, which resulted in no net
reaction for ChCl: malonic acid/ oxalic acid DES (Table 1,
entries 2, 3). Low yield of products were obtained in ChCl: urea
DES (Table 1, entry 4). However, many other organic bases such
General procedure for preparation of choline hydroxide
catalyzed synthesis of 4-aminoquinoline-2-ones (6a-6m)
Compound 3/5 (1 mmol) was dissolved in 3 mL of choline
hydroxide at room temperature and then heated for appropriate
time. After completion of reaction, cold water was added to the
reaction mixture. The precipitated solid product (6) was filtered
off, and purified by column chromatography using hexane: ethyl
acetate.
as Et N, piperidine, and pyridine, promoted the reaction quite
3
well for 3a in a short time as compared to 5a. (Table 1, entries 5-
7
). Whereas inorganic bases such as sodium hydride, potassium
hydroxide, sodium hydroxide, and potassium tert-butoxide
provided a good yield of the product as compared to organic
bases (Table 1, entries 8-11). Out of all the bases monitored,
ChOH was concluded to be the best at 80 °C and gave products
6a and 6i in 83 % and 80% yield respectively (Table 1, entry 12).
In order to screen the effect of solvent, the model reactions was
carried out using 1 equiv of ChOH in different solvents at reflux
condition (Table 1, entries 13-18). It was observed that in polar
solvents like ethanol and acetonitrile (Table 1, entries 14 & 15)
good yields of product were obtained in short reaction times as
compared to non polar solvent (Table 1, entries 16-18). In water,
Results and discussion
Preparation of 2-cyanophenylamides (3a-3h and 5a-5e)
5
0
In the first part, we carried out the reactions of 2-
aminobenzonitriles with various acid chlorides like
cyanoacetylchloride, phenyl acetyl chloride, monoethylmalonyl
chloride, and 7-methylcoumarin-4-acetyl chloride to give
1
00 it gave very low yield of the product under the same reaction
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

New Journal of Chemistry
Page 4 of 9
Table 1. Optimization study for cyclisation reaction of 3a and 5a
CN
NH2
View Article Online
DOI: 10.1039/C4NJ01281J
R2
O
O
Base/Solvent
R2
N
N
H
R1
R1
H
a, R2 = CN
a, R2 = COOEt
6a, R
2
= CN
3
5
2
6i, R = COOEt
a
a
For reactant 3a
For reactant 5a
Entry
1
Base/Solvent
f
f
Time (h)
Yield of 6a
Time (h)
24
Yield of 6i
Without catalyst/reagent
ChCl: Urea
24
10
10
10
4.5
1.5
2.5
4
NR
21
NR
NR
48
61
47
58
62
70
72
83
30
63
61
55
43
49
NR
17
NR
NR
36
57
42
51
54
69
63
80
21
64
67
50
30
51
e
b
2
11
b
3
ChCl:Malonic acid
ChCl:Oxalic acid
10
b
4
10
c
5
Et N/Ethanol
3
24
c
6
Piperidine/Ethanol
Pyridine/THF
10
c
7
11
c
8
Sodium hydride/THF
10
c
9
Potassium tert-butoxide /THF
6
9
c
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
Sodium hydroxide/Ethanol
1.5
1.5
20 min
12
1
4.5
4.5
50 min
12
c
d
e
e
e
e
e
e
Potassium hydroxide/Ethanol
ChOH
Water
Ethanol
4
Acetonitrile
Tetrahydrofuran
Dichloromethane
Toluene
1.5
2
6
10
6
12
2
2
a
b
c
d
Reaction conditions: 3a/5a (1 mmol), DES used (3 mL/ 80°C), Base used (2.5 equiv/ reflux) ChOH (3 mL/ 80 °C), ChOH used (1
equiv/ reflux), Isolated yields, NR: No reaction
f
5
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Page 5 of 9
New Journal of Chemistry
conditions (Table 1, entry 13). As solvent-free synthesis has
steric hindrance. Hence, more time was required for cyclisation
gained much current interest, it was considered important to
investigate the reaction under these conditions as well. The best
conversion was finally achieved under solvent-free conditions
using ChOH at 80 °C (Table 1, entry 12).
of 3 giving lesser yield of the 4-aminoquinoline-2-ones (Table 2,
View Article Online
2
5
entries 2, 3, 5, 6, and 10-12). All the reactions were successful
DOI: 10.1039/C4NJ01281J
and gave better yield of the products.
5
The time required for cyclisation reaction also depends upon
2
3
nature of R /R group, as the electron withdrawing power of
Synthesis of 4-aminoquinoline-2-ones in choline hydroxide
2
3
R /R group increases the cyclisation reaction becomes faster.
2
30
When R = CN, CO Et (3a-3e), reaction completed in very short
2
With the optimal conditions in hand, we extended our studies to
the variety of substrates to evaluate the scope of this methodology
and the results were presented in Table 2. The amides (3a-3h &
time and gave best yield of the 6a-6e (Table 2, entries 1-5). For
the substrate 3f, deliberately we carried out the reaction for longer
1
1
2
0
5
0
2
time to see the effect of ChOH on ester functionality (R = CO Et)
2
5
a-5e) have ArNHCOCH R type of structure; where Ar group
2
(Table 2, entry 6). It was observed that hydrolysis and
consist of cyano substituent at 2-position with respect to NH
2
1
2
35 decarboxylation results in the formation of 6f rather than desired
product. Initially, the reaction was very rapid giving
corresponding cyclized product. After that ester was hydrolyzed
to acid and then acid was decarboxylated to give 62% of 6f in 2h.
group. R may be H/ F/ Cl/ O-Cyclohexyloxy; R group may be
3
CN/ Ph/ CO Et/ 7-methylcoumarin-4-yl; and R group may be
2
CH3 or Ph. The substituent effect on the yield and rate of
cyclisation was observed.
2
1
In case of 3g and 3h (R = Ar) carbanion is better stabilized by
When R = H, then rate of cyclisation was fast and higher yield
40
aromatic ring thereby decreasing its nucleophilicity which results
of the desired product (Table 2, entries 1, 4, 7-9 and 13) was
3
1
in longer reaction time (Table 2, entries 7 and 8). When R = CH
3
observed as compared to other substituents (R = F, Cl and O-
1
or Ar (5a-5e), reaction requires less time and gave good yield of
the 6i-6m (Table 2, entries 9-13).
cyclohexyloxy). When R = F, Cl, decreased reactivity in the
cyclization due to their electron withdrawing effects. The longer
reaction time required for O-cyclohexyloxy group was due to its
O
O
O
CN
2
CN
R
O
O
CN
O
3
Cl
EtO
R
2
4
2
R3
R
1
N
H
1
N
H
R
0 oC - RT
DCM
R
o
NH
2
1
30
C
1
R
5
a-5e
3a-3h
Xylene
1
1
ChOH
R
R
R
= H, F, Cl, O-Cyclohexyloxy
ChOH
2
3
= 7-methylcoumarin-4yl, CN, Ph, COOEt
= CH , Ph
3
NH
2
O
NH2
R2
O
3
R
R1
N
H
O
1
N
H
R
6i-6m
6a-6h
4
5
Scheme 3: Synthesis of 4-aminoquinoline-2-ones in choline hydroxide
Table 2: Synthesis of 4-aminoquinoline-2-ones
Time
Yield
a
Entry
Starting Material
Products
b
(min)
(%)
NH2
CN
O
CN
O
1
20
83
74
CN
N
H
3
a
N
6
a
H
F
F
NH2
CN
CN
O
O
3
0
2
CN
N
N
H
3
b H
6b
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

New Journal of Chemistry
Page 6 of 9
View Article Online
DOI: 10.1039/C4NJ01281J
O
O
NH2
3
CN
30
69
CN
O
O
CN
N
N
H
H
c
6c
3
NH2
O
CN
O
O
O
OEt
4
5
6
25
30
75
72
62
N
OEt
3
d H
N
O
O
6
d H
F
F
NH2
CN
O
OEt
N
OEt
N
H
O
H
3
e
6e
NH2
CN
O
O
120
Cl
N
OEt
H
f
Cl
N
H
O
3
6
f
CH3
CH
3
7
CN
NH
2
O
120
74
O
O
O
N
O
6g
3
g
H
N
O
H
NH2
CN
O
8
9
8 h
50
82
80
N
H
3
h
N
H
O
6
h
NH2
O
O
CN
O
O
O
CH3
N
H
CH
3
5a
N
H
6
i
F
F
NH2 O
1
0
CN
O
CH3
5
0
72
N
CH3
N
O
H
6j
H
5
b
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Page 7 of 9
New Journal of Chemistry
View Article Online
DOI: 10.1039/C4NJ01281J
67
O
O
NH2
O
O
1
1
CN
90
O
O
CH3
N
H
CH
3
N
H
6k
5c
NH2
O
CN
O
O
CH
3
1
1
2
3
60
90
74
73
Cl
N
H
CH
3
5
d
Cl
N
H
O
6
l
NH2
O
O
CN
O
O
N
H
5
e
N
H
6
m
a
b
Reaction conditions: amide (1 mmol), choline hydroxide (3 mL), Temperature 80 °C, Isolated yields
Recovery of the ChOH
after isolation of product by filtration. The recycled ChOH was
used for the next batch with minimal loss of activity till four
consecutive runs (Fig. 1).
10
5
The recovery was very simple involving evaporation of water
1
00
8
3
83
8
1
7
9
7
5
80
60
40
20
0
Yield (%)
Fresh
First Second Third Fourth
Recycle Number
1
0
Fig. 1: Recyclability studies for product 6a
Fig. 2: FT-IR spectra of a) ChOH before reaction (blue curve) b) ChOH after four runs (red curve)
| Journal Name, [year], [vol], 00–00 This journal is © The Royal Society of Chemistry [year]
6

New Journal of Chemistry
Page 8 of 9
FT-IR analysis
Proposed mechanism
The compound having covalent bond absorbs various frequencies
of electromagnetic radiation in the infrared region of the
electromagnetic spectrum. Infrared spectrum is used to determine
structural information about a molecule. ChOH before reaction
and after reaction were characterized using ATR-FTIR
View Article Online
DOI: 10.1039/C4NJ01281J
1
5
Although the mechanism illustrating the role of such ChOH in 4-
aminoquinoline-2-ones synthesis is yet to be confirmed, we
suggest a mechanism that highlights the probable role of ChOH
in synthesis. Hydroxide ion of ChOH forms hydrogen bonding
with acidic protons of amide (Fig. 3). ChOH assist in improving
reactivity and finally promoting cyclization to form the 4-
aminoquinoline-2-ones core.
5
-
1
spectroscopy. The absorption peak at around 3365 cm is the
characteristic of O-H stretching vibration. The band at 1236 and
20
-
1
1
087 cm result from C-N and C-O stretching. Also band at 888
-
1
1
0
and 628 cm is due to C-H bending vibration. There is no change
observed in the IR spectra of ChOH before the reaction and after
four runs (fig. 2).
H
3
C
H
3
C
H
3
C
C
H
3
C
N
H
3
C
N
H
3
C
N
H
3
C
OH
H
3
C
OH
H
3
OH
OH
N
OH
OH
N
N
NH
ChOH
80 o
CH
N
3
R
1
CH
N
3
H
H
C
CH
NH
3
3
NH
R2
H
3
C
CH
3
C
O
R
1
R1
H
H
R
2
H
O
OH
O
OH
R
2
H
Substituted Amide
OH
OH
Choline Hydroxide
Abstraction of proton from active methylene group
Carbanion attacks cyano group
H
3
3
C
C
H
3
C
N
H
OH
OH
CH
N
3
H
OH
NH
2
H
3
C
3
CH Aromatization
H
R
2
N
CH
N
3
N
R
2
R
2
OH
H
3
C
CH
3
N
H
O
H
H
OH
R
1
OH
N
H
O
N
H
O
R
1
R
1
OH
Aromatization leading to desired product
4-Amino-quinoline-2-ones
Fig. 3: Mechanism proposing the role of ChOH in synthesis of 4-aminoquinoline-2-ones derivatives
2
5
Conclusion
Acknowledgements
45
In this study, we have described an efficient and practical
methodology for the synthesis of 4-aminoquinoline-2-ones in
ChOH. Moreover, the influence of substituent type (-CN,
A.K.S. is thankful to the Institute of Chemical Technology and
UGC-CAS for providing financial assistance and IIRBS-
Kottayam for spectral analysis.
-
COCH3, -COPh, -CO Et, -Ph, 7-methylcoumarin-4-yl
2
3
3
4
0
5
0
substituents) and position on the rate of cyclisation of amide to 4-
Notes and references
1
aminoquinoline-2-ones was investigated. When R = H, then rate
1
of cyclisation was fast as compared to other substituents (R = F, 50 † Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
Cl and O-Cyclohexyloxy). The time required for cyclisation
2
3
reaction depends upon nature of R /R group. The electron
withdrawing cyano group increases the cyclisation reaction rate
2
3
References
and gave high yield of the product (6a-6c) and when R /R = Ar
3g and 3h), reaction required longer time. This may be due to
(
55
stabilization of carbanion by benzene ring. FTIR spectra of fresh
ChOH and recycled ChOH remain unchanged. Hence, ChOH can
be recycled and reused. These features will facilitate this
procedure to find extensive applications in the field of organic
synthesis.
1. R. W. Carling, P. D. Leeson, K. W. Moore, C. R. Moyes, M.
Duncton, M. L. Hudson, R. Baker, A. C. Foster, S.
Grimwood, J. A. Kemp, G. R. Marshall, M. D. Tricklebank
and K. L. Saywell, J. Med. Chem., 1997, 40, 754–765.
60 2. P. A. Renhowe, S. Pecchi, C. M. Shafer, T. D. Machajewski,
E. M. Jazan, C. Taylor, W. Antonios-McCrea, C. M.
McBride, K. Frazier, M. Wiesmann, G. R. Lapointe, P. H.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

Page 9 of 9
New Journal of Chemistry
Feucht, R. L. Warne, C. C. Heise, D. Menezes, K. Aardalen,
H. Ye, M. He, V. Le, J. Vora, J. M. Jansen, M. E. Wernette-
Hammond and A. L. Harris, J. Med. Chem., 2009, 52, 278–
View Article Online
DOI: 10.1039/C4NJ01281J
2
92.
5
0
5
0
5
0
5
0
5
0
5
3. P. A. Renhowe, S. Pecchi, T. D. Machajewski, C. M. Shafer,
E. M. Jazan, C. Taylor, W. B. McCrea, C. M. McBride, E.
Jazan, M. E. Wernette-Hammond and A. L. Harris, WO
Pat.0222598A1 (2002).
4
.
C. Tachdjian, D. S. Karanewsky, X-Q. Tang, X. Li, F. Zhang,
G. Servant, Q. Chen, V. Darmohusodo, R. Fine, J. R.
Fotsing, J. R. Hammaker, X. Kang, R. D. A. Kimmich, B.
Klebansky, H. Liu, G. Petrovic, M. Rinnova, S.
Adamski-Werner, J. Yamamoto, H. Zhang, A. Zlotnik, M.
Zoller and K. Zoller, US Pat.20110224155A (2011).
1
1
2
2
3
3
4
4
5
5
5. A. C. Veronese, R. Callegari and S. A. A. Salah, Tetrahedron
Lett., 1990, 31, 3485–3488.
6
7
8
.
.
.
A. C. Veronese, R. Callegari and C. F. Morelli, Tetrahedron,
995, 51, 12277–12284.
A. Walser, G. Silverman, T. Flynn and R. I. Fryer, J.
Heterocycl. Chem., 1975, 12, 351–358.
M. Rowley, J. J. Kulagowski, a P. Watt, D. Rathbone, G. I.
Stevenson, R. W. Carling, R. Baker, G. R. Marshall, J. a
Kemp, a C. Foster, S. Grimwood, R. Hargreaves, C. Hurley,
K. L. Saywell, M. D. Tricklebank and P. D. Leeson, J. Med.
Chem., 1997, 40, 4053–4068.
1
9
1
.
M. Rehwald, K. Gewald, H. Lankaun and K. Unverferth,
Heterocycles, 1997, 45, 483–492.
0. E. J. Paul, P. A. Renhowe, S. Pecchi, T. D. Machajewski, C.
M. Shafer, C. Taylor, W. R. McCrea JR, C. M. McBride, E.
Jazan, US Pat. 2003028018A1 (2003).
1
1
1. W. Steinschifter and W. Stadlbauer, J. Prakt.
Chemie/Chemiker-Zeitung, 1994, 336, 311–318.
2. W. Stadlbauer and T. Kappe, Monatshefte fr Chemie Chem.
Mon., 1982, 113, 751–760.
13. T. K. W. Stadlbauer, Synthesis, 1981, 833–834.
1
4. R. B. Toche, R. A. Janrao, S. M. Bagul, S. P. Patil, B. P.
Pagar and P. S. Nikam, J. Fluoresc., 2011, 21, 1617–1624.
5. C. Ruß and B. König, Green Chem., 2012, 14, 2969–2982.
6. Y. A. Sonawane, S. B. Phadtare, B. N. Borse, A. R. Jagtap
and G. S. Shankarling, Org. Lett., 2010, 12, 1456–1459.
1
1
1
1
7. P. M. Pawar, K. J. Jarag and G. S. Shankarling, Green Chem.,
2
011, 13, 2130–2134.
8. H. R. Lobo, B. S. Singh and G. S. Shankarling, Catal.
Commun., 2012, 27, 179–183.
19. S. B. Phadtare, K. J. Jarag and G. S. Shankarling, Dye.
Pigment., 2013, 97, 105–112.
2
2
2
2
0. A. K. Sanap and G. S. Shankarling, Catal. Commun., 2014,
9, 58–62.
1. U. N. Yadav and G. S. Shankarling, J. Mol. Liq., 2014, 19,
137–141.
4
2. A. K. Sanap and G. S. Shankarling, RSC Adv., 2014, 4,
3
4938–34943.
3. J. Shao, X. Huang, S. Wang, B. Liu and B. Xu, Tetrahedron,
012, 68, 573–579.
24. K. Chakraborty and C. Devakumar, J. Agric. Food Chem.,
006, 54, 6800–6808
2
2
.
8
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]