NH4OAc-promoted cascade approach towards aberrant synthesis of chromene-fused quinolinones

Article abstract of DOI:10.1002/ejoc.201801292

A concise cascade strategy for the synthesis of 6H-chromeno[4,3-b]quinolin-6-ones was developed from 4-hydroxycoumarins and arylhydrazine hydrochlorides in DMSO. The synthetic strategy relies on dual role of ammonium acetate in generating 4-aminophenyl coumarin from arylhydrazine via aryl radical formation, and Csp²-H formylation of coumarin using DMSO as a methine source. The strategy is scalable, and an array of arylhydrazine hydrochlorides delivered chromene-fused quinolinones in good to excellent yields.

Full text of DOI:10.1002/ejoc.201801292

A Journal of
Accepted Article
Title: NH4OAc-promoted Cascade Approach towards Aberrant
Synthesis of Chromene-fused Quinolinones
Authors: Santosh Kumari, S. M. Abdul Shakoor, Datta Markad, Sanjay
K. Mandal, and RAJEEV Sakhuja
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801292
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801292
Supported by

10.1002/ejoc.201801292
European Journal of Organic Chemistry
FULL PAPER
NH4OAc-promoted Cascade Approach towards Aberrant
Synthesis of Chromene-fused Quinolinones
Santosh Kumari,[a] S. M. Abdul Shakoor,[a] Datta Markad,[b] Sanjay K. Mandal,[b] Rajeev Sakhuja*[a]
Abstract: A concise cascade strategy for the synthesis of 6H-
chromeno[4,3-b]quinolin-6-ones was developed from 4-
chemists towards their construction, in the past decade.
Traditional strategies reported for the synthesis of 6H-
chromeno[4,3-b]quinolin-6-ones include, cyclization of 4-chloro-
3-formylcoumarin (obtained by formylation using toxic POCl3)
with aromatic amines or aryl isocyanates.[5a],[14] However, the
disadvantages associated with Vilsmeier–Haack formylation has
led to the use of aldehydes as methine source substrate, for
preparing 6H-chromeno[4,3-b]quinolin-6-ones. Under this realm,
Choudhury and co-workers disclosed a bismuth triflate-catalyzed
strategy for preparing 6H-chromeno[4,3-b]quinolin-6-ones via
hydroxycoumarins and arylhydrazine hydrochlorides in DMSO. The
synthetic strategy relies on dual role of ammonium acetate in
generating aromatic amine from arylhydrazine via aryl radical
formation, and Csp2-H formylation of coumarin using DMSO as a
methine source. The strategy is scalable, and an array of
arylhydrazine hydrochlorides delivered chromene-fused quinolinones
in good-to-excellent yields.
multicomponent
reaction
between
4-hydroxycoumarin,
aldehydes and aromatic amines under neat conditions (Scheme
1a).[15] Sashidhara group reported iodine-catalyzed tandem
process for annulation between 4-hydroxycoumarin, aromatic
aldehydes, and aromatic amines under MW irradiation, affording
6H-chromeno[4,3-b]quinolin-6-ones in high yields (Scheme
1b).[12] Yao and co-workers synthesized 6H-chromeno[4,3-
b]quinolin-6-ones through reductive cyclization between 4-
hydroxycoumarin and ortho-nitrobenzaldehydes using excess of
Fe and acetic acid (Scheme 1c).[16] With the advent of elegant
Csp2-H formylation protocols,[17] Su and co-workers reported a
Cu-catalyzed cyclization protocol from 4-(phenylamino)-2H-
chromen-2-ones, employing DMF as formyl-generating source
and TBPB as oxidant, affording functionalized 6H-chromeno[4,3-
b]quinolin-6-ones in moderate-to-good yields (Scheme 1d).[18] In
spite of reasonable advancements, designing metal-
free/oxidant-free strategy from commercially available starting
materials to obtain 6H-chromeno[4,3-b]quinolin-6-ones in a
single step is highly desirable.
Introduction
The accountability of fluorescent fused heterocycles in the
developed organic light-emitting diodes (OLEDs),[1] biological
markers,[2] sensors,[3] organic rectifiers and dyes[4] has received
tremendous hike in recent years. Strikingly, chromene nucleus
has displayed a center-stage role in designing a number of
fascinating fluorescent heterocyclic architectures of immense
potential in medicinal and material chemistry.[5] In particular,
chromene-fused quinolines constitute an integral part of several
natural products including santiagonamine,[6] and have been
identified as antibacterial,[7] and anticancer agents,[8] sensors,[9]
dyes for mitocondrial imaging,[10] estrogen receptor β-selective
ligands,[11] selective non-steroidal progesterone receptor
modulators,[12] and glucocorticoid modulators[13] (Figure 1).
Metal-free cascade strategies have developed a significant
repute for constructing different heterocycles in an
environmentally sustainable and atom-economical manner.[19] In
this regard, the use of NH4OAc as an inexpensive nitrogen
source has been exemplified in various C-C/C-X bond
forming/breaking transformations.[20] In addition, it is reported as
a promoter for Pummerer reaction for successful formylation of
indoles using DMSO as carbonyl source.[21]
On the other hand, arylhydrazines are valuable coupling
partners in organic synthesis, capable of constructing aryl-
(hetero)aryl C-C bonds via generating aryl radical[22] under
appropriate conditions. To the best of our knowledge, the use of
arylhydrazines remains unexplored for the synthesis of
chromene-fused quinolinones. We envisioned the dual use of
NH4OAc to promote Pummerer reaction for C-3 formylation of
coumarin using DMSO as a methine source, and simultaneously
act as a nitrogen source for trapping aryl radical that is expected
to generate from arylhydrazine, to consecutively afford 6H-
chromeno[4,3-b]quinolin-6-ones in a tandem manner. With our
continuous zeal in developing C-H activation based cascade
strategies,[23] and inspired from significant applications of 6H-
Figure 1. Selective examples of reported chromene-fused quinolines
Further, the applicative value of substituted 6H-chromeno[4,3-
b]quinolin-6-ones has stimulated considerable interest of organic
[a]
[b]
Ms. S. Kumari, Dr. S. M. A. Shakoor, Prof. R. Sakhuja
Department of Chemistry
Birla Institute of Technology & Science, Pilani, Rajasthan, 333031,
India
E-mail: rajeev.sakhuja@pilani-bits-pilani.ac.in
Mr. D. Markad, Prof. S. K. Mandal
Department of Chemical Sciences, Indian Institute of Science
Education and Research Mohali, Sector 81, S.A.S. Nagar, Manuali
P.O., Punjab 140306, India
chromeno[4,3-b]quinolin-6-ones,
herein,
we
report
an
operationally simple ammonium-promoted method for the one-
pot synthesis of 6H-chromeno[4,3-b]quinolin-6-ones from 4-
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801292
European Journal of Organic Chemistry
FULL PAPER
hydroxycoumarin, arylhydrazine hydrochlorides using NH4OAc in
DMSO (Scheme 1e).
Table 1.Selected Optimization conditions[a] for the synthesis of 3aa
Nitrogen
source
Yield
of3a
a
Reaction Conditions
Oxidant
(equiv)
Entry
T
Time
(equiv)
Solvent
(%)[b]
( oC)
130
130
130
130
130
130
130
130
130
70
(h)
5
6
8
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
1.
2.
3.
4.
5.
NH4OAc (1)
NH4OAc (1)
NH4OAc (1)
NH4OAc (2)
NH4OAc (3)
NH4OAc (4)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
NH4OAc (3)
(NH4)2CO3 (3)
NH4Cl (3)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
Air
Air
Air
Air
Air
Air
Air
Air
Air
35
42
43
50
70
71
70
<10
<10
-
-
0
0
0
73
50
30
20
26
6.
7.[c]
8.
9.
Scheme 1. Summary of previous and present synthesis of 6H-chromeno[4,3-
b]quinolin-6-one
DMA
10.
11.
12.[d]
13.[d]
14.[d]
15.
16.
17.
18.
19.
MeOH
Dioxane
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Air
Air
115
130
130
130
130
130
130
130
130
TBHP (3)
H2O2 (3)
K2S2O8 (3)
O2
Results and Discussion
From the outset of the proposed work, we began investigating
the model reaction between 4-hydroxycoumarin (1a) (1 equiv),
and phenylhydrazine hydrochloride (2a) (1.2 equiv) under
ammonium-promoted conditions (Table 1). Gratifyingly, we
witnessed the formation of a product in 35% yield after heating
1a and 2a using NH4OAc (1 equiv) at 130 °C in DMSO for 5 h
under ambient conditions (Table, 1 entry 1). Purification and
Air
Air
Air
Air
NH2NH2 (3)
Aq. NH3
[a] 1a (0.30 mmol), 2a (0.36 mmol), nitrogen source (as specified), oxidant
(as specified, if applicable), solvent (3 mL) under air (except for entry 12-15).
[b] Isolated yields. [c] 1a (0.30 mmol), 2a (0.45 mmol). [d] Nitrogen
atmosphere.
characterization of the product using H NMR, 13C NMR, HRMS
1
unequivocally confirmed it to be 6H-chromeno[4,3-b]quinolin-6-
one (3aa). This unprecedented formation of a chromene-fused
quinolinone from phenylhydrazine hydrochloride as an aryl
source propel us to further optimize this tandem protocol with
respect to time, solvent, and reactant/reagent concentrations.
Time optimization studies revealed that heating the model
reaction up to 6 h produces an increment in the yield of 3aa to
42%, however no further noticeable amelioration in its yield was
observed by further increasing the reaction time (Table 1, entries
2-3). Delightfully, a step-wise change in the equivalents of
NH4OAc from 1 to 3 aids an augmentation in the yield of 3aa to
70%, albeit the use of 4 equivalents of NH4OAc produced no
further noticeable change (Table 1, entries 4-6). Also, no
enrichment in the yield of 3aa was noticed by increasing the
concentration of 2a to 1.5 equivalents (Table 1, entry 7). Next,
solvent screening studies were performed which suggested
DMF and DMA to be poor solvents for the desired
transformation, yielding <10% of 3aa, while MeOH and 1,4-
dioxane to be completely unsuitable as expected (Table 1,
entries 8-11). The use of external oxidants were next
investigated; the results of which inferred that no product was
formed in presence of TBHP, H2O2, K2S2O8 under nitrogen
atmosphere, while the use of molecular O2 furnished 3aa in 73%
yield (Table 1, entries 12-15). Finally, the use of other amine
sources, including (NH4)2CO3, NH4Cl, NH2NH2 and NH3 were
explored; these amine sources produced lower yields of 3aa
under similar reaction conditions. (Table 1, entries 16-19).
Having optimized reaction conditions in hand, we next
investigated the generality of this cascade process with a wide
range of arylhydrazine hydrochlorides (2a-j) as coupling partners
with 4-hydroxycoumarin (1a) (Scheme 2).
Scheme 2. Substrate Scope of arylhydrazine hydrochlorides
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Arylhydrazine hydrochlorides possessing electron-donating and
electron-withdrawing groups were well tolerated under optimized
Here again, electronically-rich arylhydrazine hydrochlorides
exhibited better reactivity over the electron-deficient ones. The
only exception in this case was the reaction of 4-
cyanophenylhydrazine hydrochloride with 1b, which afforded
conditions
to
deliver
corresponding
substituted
6H-
chromeno[4,3-b]quinolin-6-ones (3aa-ai) in 66-85% yields.
Overall, some variation in the electronic environment of
arylhydrazine hydrochlorides has shown noticeable results.
Electronically-rich arylhydrazine hydrochlorides (2b-f: R2 = 4-Me,
2-Me, 4-OMe, 2,4-diMe, 3,4-diOMe) exhibited good reactivity
and furnished substituted chromene-fused quinolinones (3ab-af)
in 74-85% yields, while moderately electronically-deficient
arylhydrazine hydrochlorides (2g-i: R2 = F, Cl, Br) afforded the
cyclized products 3ag-ai in comparatively lower yields (66-69%).
Unfortunately, the use of 4-cyanophenylhydrazine hydrochloride
(2j) yielded only 10% of the cyano functionalized 6H-
chromeno[4,3-b]quinolin-6-one (3aj). The lower reactivity of
arylhydrazine possessing electron withdrawing group (CN) could
be either due to instability of the corresponding aryl radical,
and/or due to lower nucleophilicity of in situ generated
substituted 4-aminoaryl coumarin, to promote C-3 formylation
and subsequent nucleophilic addition.
cyano
functionalized
7-(diethylamino)-6H-chromeno[4,3-
b]quinolin-6-one 3aj in only 8% yield. Also, electron-deficient 6-
bromo-4-hydroxycoumarin (1c) showcased moderate reactivity
for a number of arylhydrazine hydrochlorides (2a, 2e, 2h & 2i),
affording their corresponding chromene-fused quinolinones 3ca,
3ce, 3ch & 3ci in 56-72% yields. On the other hand, methyl and
methoxy substituted 4-hydroxycoumarins (1d & 1e) displayed
slightly better reactivity towards different arylhydrazine
hydrochlorides (2a, 2e, 2g) to furnished their corresponding
chromene-fused quinolinones (3da, 3de, 3ee & 3eg) in 58-74%
yields. All the synthesized compounds were isolated by column
chromatography, and characterized by detailed spectroscopic
analysis. To assess the scalability of this metal-free cascade
process, a gram scale reaction was performed between 1a and
2a under optimized conditions to afford 3aa in 68% yield (1.017
g), which is similar to that obtained on a smaller scale (Scheme
4).
With our advent interest in synthesizing highly fluorescent
heterocycles, we next explored the performance of 7-(N,N-
diethylamino)-4-hydroxycoumarin (1b) with
a
variety of
arylhydrazine hydrochlorides under optimized conditions.
Pleasingly, 1b reacted quite well with electron-rich and electron-
deficient arylhydrazine hydrochlorides (2a-c, 2e-i, 2k-l),
affording their corresponding chromene-fused quinolinones
(3ba-bc, 3be-bi, 3bk-bl) in 58-78% yields (Scheme 3).
Scheme 4. Gram scale synthesis of 3aa
To further confirm the proposed structure, as a representative
example, single crystals of 3ba were grown from a mixture of
ethyl acetate and hexane for X-ray diffraction (XRD) studies.
̅
Compound 3ba crystallizes in the R 3 (No. 148) group. An
ORTEP diagram of the 3ba (CCDC No. 1862858) is shown in
Figure 2.
Figure 2. ORTEP diagram of 3ba
To gain insights into the mechanistic pathway, a series of
preliminary experiments were performed. Reaction of 4-
hydroxycoumarin (1a) and phenylhydrazine hydrochloride (2a) in
DMSO at 130 °C produced no product at all, thereby indicating a
crucial participation of NH4OAc in this cascade process (Scheme
5ia). Reaction of 1a with NH4OAc (3 equiv) under neat
o
conditions at 130 C for 6 h furnished 4-aminocoumarin (1aʹ) in
only 40% yield, which on further reaction with 2a in DMSO
(without NH4OAc, Scheme 5ib#) or using NH4OAc (in absence of
DMSO, Scheme 5ib@) did not yield 3aa at all. It is worth
Scheme 3. Substrate scope of 4-hydroxycoumarins and arylhydrazine
hydrochlorides
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10.1002/ejoc.201801292
European Journal of Organic Chemistry
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mentioning that 4-aminophenyl coumarin (D) was observed in
ESI-MS of their respective reaction mixtures (Supporting
Information). On the other hand, reaction of 4-aminocoumarin
(1aʹ) with 2a using NH4OAc in DMSO under optimized
conditions afforded 3aa in 65% yield (Scheme 5ib). No
prominent product was isolated by reacting 2a with NH4OAc, in
presence or absence of DMSO under described reaction
conditions (Scheme 5ic). Notably, the failure of model reaction to
proceed in presence of radical scavenger TEMPO (3 equiv)
advocates about the involvement of radical species during the
course of reaction mechanism (Scheme 5iia). The reaction of
aniline instead of phenylhydrazine with 1a under optimized
conditions yielded the product 3aa, albeit in only 20% after 6 h
under ambient conditions, whereas trace amount of 3aa was
observed (on TLC) in nitrogen atmosphere (Scheme 5iib). This
indicates a crucial role of atmospheric oxygen in the reaction
pathway. To further confirm the formation of 4-(phenylamino)-
2H-chromen-2-one (D) as one of the intermediates in the
reaction between 1a and 2a, D was synthesized by standard
procedure.[18] Pleasingly, D on further heating in DMSO using
ammonium acetate (3 equiv) yielded the desired product 3aa in
60% yield after 8 h, thereby indicating that its formation is
involved in the reaction mechanism (Scheme 5iic).
Interestingly, aniline was isolated (via column chromatography)
as one of the intermediates in only minor amounts from the
mixture obtained by reacting 1a and 2a after 2 h (Scheme 5iii),
however, this is contradictory to the results obtained in Scheme
5ic. Thus, it appears that aniline formation might not be involved
in the operating reaction mechanism, and aniline could be a
result of a side reaction. Contentedly, the formation of 3aaʹ in
presence of deuterated DMSO-d6 affirmed DMSO as a methine
source in the disclosed transformation (Scheme 5iv).
Unfortunately, no other intermediate was isolated in pure form,
even on repeated attempts. Thus, we planned to monitor the
model reaction via analyzing its mass spectra (Scheme 5v). To
our delight, ESI-HRMS of the crude mixture recorded after 1 h
detected the presence of the peaks at m/z 238.0897, 268.0933
and 266.0744, corresponding to the molecular formula
C15H12NO2 [M + H]+, C16H14NO3 [M + H]+ and C16H12NO3 [M +
H]+, respectively, which indicated the possible formation of
intermediates D, H, and I during the course of the reaction
(supporting Information). After all the investigations, it appears
that the intermediate, 4-aminophenyl coumarin (D) has been
formed by the reaction of in situ generated aniline (C) with 4-
hydroxycoumarin (1a), or by N-arylation of in situ generated 4-
aminocoumarin (1aʹ).
Based upon the above studies and literature reports,[5],[17],[21],[24]
a
postulated mechanism is illustrated in scheme 6. The overall
process consists of two main steps that could be assumed to
proceed either simultaneously or consecutively. The first step of
the reaction is believed to be initiated by the decomposition of
phenylhydrazine hydrochloride (2a) to phenyl radical (C) via
formation of A and diazonium radical (B) via single electron
transfer (SET) mechanism.[24] Subsequently, amination of 4-
hydroxycoumarin (1a) with ammonium acetate, followed by
arylation by phenyl radical (C) furnishes 4-(phenylamino)-2H-
chromen-2-one (D). Thereafter, the second step involves the
activation of DMSO by ammonium acetate to produce thionium
ion (E), which undergoes a nucleophilic attack by 1a to produce
F via Pummerer-type reaction, as established by Cheng.[21] The
sulfur atom in F attacks another molecule of thionium ion (E) to
generate intermediate G, which upon nucleophilic attack by
water affords C-3 hydroxymethylation intermediate (H).
Subsequently oxidation of
H takes place to produce 4-
(phenylamino)-2H-chromen-2-one-3-carbaldehyde (I). Finally,
aldol-type intramolecular nucleophilic addition in I, followed by
dehydration affords the desired product 3aa. However, there is
still one question that remains to be addressed, i.e. the source of
water (as nucleophile) in the proposed mechanism. We
anticipated that either the hygroscopic behavior of ammonium
acetate under ambient conditions, or nucleophilic substitution of
hydroxyl group with aniline could be possible source(s) of water
in the reaction mixture.
Scheme 5. Control experiments for investigation of the mechanism
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10.1002/ejoc.201801292
European Journal of Organic Chemistry
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uncorrected. High resolution mass spectra were recorded with a TOF
analyzer spectrometer by using electrospray mode. IR spectra were
recorded on Shimadzu IR Prestige-21 FT-IR spectrophotometer. Flash
column chromatography was performed on silica gel, 60−120 mesh.
Analytical and preparative thin-layer chromatography was carried out on
silica gel 60 F-254 plates. Products were visualized using UV and shown
blue colour and yellow colour under uv light.
General procedure for the synthesis of 6H-chromeno[4,3-b]quinolin-
6-ones
A mixture of 4-hydroxycoumarin (1, 0.30 mmol, 1.0 equiv), arylhydrazine
hydrochloride (2, 0.36 mmol, 1.2 equiv), NH4OAc (0.90 mmol, 3.0 equiv)
were heated in DMSO (3.0 mL) at 130 °C under ambient conditions for 6-
8 h. On completion of the reaction as indicated by TLC, the reaction
mixture was cooled to room temperature, and diluted with ice-water. The
mixture was extracted with ethyl acetate (3 × 20 mL), and the organic
layer was separated and dried over Na2SO4. The organic layer was
concentrated, and the crude product was subjected to silica gel column
chromatography [SiO2 (100-200 mesh), with (hexanes/EtOAc, 19:1) as
the eluent to afford pure 6H-chromeno[4,3-b]quinolin-6-one (3).
6H-Chromeno[4,3-b]quinolin-6-one (3aa): White solid; yield: 52.3 mg
(70%); mp: 223–224 °C (lit.[18] 221.9−223.1 °C); 1H NMR (400 MHz,
CDCl3) δ 9.22 (s, 1H), 8.78 (dd, J = 7.9, 1.5 Hz, 1H), 8.24 (d, J = 8.6 Hz,
1H), 8.02 (d, J = 8.2 Hz, 1H), 7.96 – 7.91 (m, 1H), 7.68 – 7.59 (m, 2H),
7.47 – 7.39 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.4, 152.7, 151.1,
149.6, 141.1, 133.4, 132.4, 129.6, 129.4, 127.4, 127.3, 125.3, 125.0,
Scheme 6. Plausible mechanism
119.6, 117.4, 115.8; IR (Ṽ, cm-1): 3055, 3013, 1735, 1604, 1496, 1242,
+
1172, 1033, 987, 756; HRMS (ESI-TOF) (m/z) calculated C16H10NO2
:
248.0706; found 248.0707 [M + H]+.
Conclusions
9-Methyl-6H-chromeno[4,3-b]quinolin-6-one (3ab): White solid; yield:
58.5 mg (74%); mp: 211–213 °C (lit.[18] 234.4−235.1 °C); 1H NMR (400
MHz, CDCl3) δ 9.12 (s, 1H), 8.77 (dd, J = 7.8, 1.0 Hz, 1H), 8.14 (d, J =
9.2 Hz, 1H), 7.76 (d, J = 6.8 Hz, 2H), 7.64 – 7.57 (m, 1H), 7.47 – 7.38 (m,
2H), 2.61 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.5, 152.5, 149.8,
148.8, 140.1, 137.6, 135.9, 132.1, 129.2, 127.9, 127.3, 125.1, 124.9,
119.7, 117.3, 115.7, 21.7; IR (Ṽ, cm-1): 2962. 2919, 1728, 1597, 1489,
1458, 1303, 1180, 1056, 1026, 802, 748; HRMS (ESI-TOF) (m/z)
calculated C17H12NO2 : 262.0863; found 262.0862 [M + H]+.
In summary we have developed an efficient, atom-economical
and metal-free cascade process for the synthesis of coumarin-
fused quinolinones; wherein DMSO, NH4OAc and arylhydrazine
served as methine, nitrogen and aryl sources, respectively. The
deuterium study implies that the carbon added is from the
methyl group of DMSO, with the inexpensive, economical
reagent, easy availability of the substrates, and moderate
functional group tolerability. This protocol could be recognized
as an inexpensive and opens a new avenue for the green and
challenging synthesis of chromeno-quinoline derivatives
11-Methyl-6H-chromeno[4,3-b]quinolin-6-one (3ac): White solid; yield:
59.3 mg (75%); mp: 221–223 °C (lit.[18] 209.6−211.7 °C); 1H NMR (400
MHz, CDCl3) δ 9.23 (s, 1H), 8.93 – 8.83 (m, 1H), 7.90 (d, J = 8.1 Hz, 1H),
7.83 – 7.77 (m, 1H), 7.65 – 7.60 (m, 1H), 7.60 – 7.54 (m, 1H), 7.50 – 7.
47 (m, 1H), 7.46 – 7.42 (m, 1H), 2.98 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.5, 152.6, 149.9, 148.2, 140.9, 137.7, 133.1, 132.1, 127.2,
127.2, 127.2, 125.2, 124.8, 120.0, 117.3, 115.3, 17.9; IR (Ṽ, cm-1): 3066,
2970, 1728, 1612, 1489, 1411, 1350, 1118, 1018, 840, 748; HRMS (ESI-
TOF) (m/z) calculated C17H12NO2+ : 262.0863; found 262.0859 [M + H]+.
Experimental Section
General materials and methods
All reagent and chemical were purchased from commercial source and
used as received. Required solvent for reaction were dried by standard
procedures prior to use. All reactions were performed under air
atmosphere, unless otherwise noted. 1H NMR spectra were recorded on
400 MHz spectrometer and chemical shifts are reported in δ units, parts
per million (ppm), and referred to the internal standard TMS set as 0.00
ppm , relative to residual chloroform (7.26 ppm) in the deuterated
solvent. Data are reported as follows: the following abbreviations were
used to describe peak splitting patterns : s = singlet, d = doublet, t =
triplet, dd = doublet of doublet and m = multiplet. Coupling constants J
were reported in Hz. The 13C NMR spectra were reported in ppm relative
to deuterochloroform (77.0 ppm). Melting points were determined on a
capillary point apparatus equipped with a digital thermometer and are
9,11-Dimethyl-6H-chromeno[4,3-b]quinolin-6-one (3ad): White solid;
yield: 65.0 mg (78%); mp: 228–230 °C (lit.[18] 219.8−220.5 °C); 1H NMR
(400 MHz, CDCl3) δ 9.07 (s, 1H), 8.81 (dd, J = 7.9, 1.6 Hz, 1H), 7.62 –
7.57 (m, 3H), 7.47 – 7.39 (m, 2H), 2.91 (s, 3H), 2.56 (s, 3H).; 13C NMR
(100 MHz, CDCl3) δ 161.7, 152.5, 148.8, 147.6, 140.1, 137.3, 137.3,
135.8, 131.8, 127.5, 125.8, 125.1, 124.8, 120.2, 117.3, 115.4, 21.7, 17.8;
IR (Ṽ, cm-1): 2962, 2924, 1728, 1597, 1496, 1373, 1257, 1087, 894, 748;
+
HRMS (ESI-TOF) (m/z) calculated C18H14NO2
: 276.1019; found
276.1003 [M + H]+.
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10.1002/ejoc.201801292
European Journal of Organic Chemistry
FULL PAPER
9-Methoxy-6H-chromeno[4,3-b]quinolin-6-one (3ae): White solid;
δ 9.07 (s, 1H), 8.47 (d, J = 9.0 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.91 (d,
J = 8.0 Hz, 1H), 7.86 – 7.80 (m, 1H), 7.55 – 7.48 (m, 1H), 6.71 (dd, J =
9.0, 2.5 Hz, 1H), 6.52 (d, J = 2.5 Hz, 1H), 3.46 (q, J = 7.1 Hz, 4H), 1.26
(t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.3, 154.7, 151.5,
151.1, 150.6, 140.9, 133.0, 129.4, 128.9, 126.3, 126.2, 126.0, 114.7,
109.1, 107.3, 97.9, 44.8, 12.6; IR (Ṽ, cm-1): 2962, 2924, 1720, 1597,
1442, 1350, 1273, 1126, 1018, 941, 817, 779; HRMS (ESI-TOF) (m/z)
calculated C20H19N2O2+ : 319.1441; found 319.1459 [M + H]+.
1
yield: 62.9 mg (75%); mp: 234–2 36 °C (lit.[18] 233.5−235.0 °C); H NMR
(400 MHz, CDCl3) δ 9.14 (s, 1H), 8.78 (dd, J = 7.9, 1.6 Hz, 1H), 8.18 (d, J
= 9.3 Hz, 1H), 7.64 – 7.58 (m, 2H), 7.48 – 7.41 (m, 2H), 7.26 (d, J = 2.8
Hz, 1H), 4.02 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.6, 158.4, 152.3,
147.7, 147.5, 139.0, 131.8, 131.0, 128.5, 127.1, 124.9, 124.9, 119.9,
117.3, 115.9, 105.6, 55.8; IR (Ṽ, cm-1): 3052, 2986, 1735, 1620, 1496,
1381, 1234, 1180, 1087, 948, 748; HRMS (ESI-TOF) (m/z) calculated
C17H12NO3+ : 278.0812; found 278.0800 [M + H]+.
3-(Diethylamino)-9-methyl-6H-chromeno[4,3-b]quinolin-6-one (3bb):
1
9,10-Dimethoxy-6H-chromeno[4,3-b]quinolin-6-one (3af): White solid;
yield: 79.0 mg (85%); mp: 280–282 °C; 1H NMR (400 MHz, CDCl3) δ
9.04 (s, 1H), 8.75 (dd, J = 7.8, 1.4 Hz, 1H), 7.62 – 7.57 (m, 1H), 7.56 (s,
1H), 7.49 – 7.39 (m, 2H), 7.22 (s, 1H), 4.16 (s, 3H), 4.10 (s, 3H).; 13C
NMR (100 MHz, CDCl3) δ 161.8, 156.0, 152.4, 150.8, 149.3, 148.1,
137.9, 131.7, 124.8, 124.7, 123.6, 119.9, 117.4, 114.0, 107.6, 105.8,
Yellow solid; yield: 52.0 mg (73%); mp: 179–181 °C; H NMR (400 MHz,
CDCl3) δ 8.99 (s, 1H), 8.47 (d, J = 9.0 Hz, 1H), 8.02 (d, J = 9.2 Hz, 1H),
7.67 (d, J = 4.5 Hz, 2H), 6.72 (dd, J = 9.0, 2.3 Hz, 1H), 6.54 (d, J = 2.2
Hz, 1H), 3.47 (q, J = 7.1 Hz, 4H), 2.56 (s, 3H), 1.26 (t, J = 7.1 Hz, 6H);
13C NMR (100 MHz, CDCl3) δ 162.5, 154.5, 150.9, 150.2, 149.9, 140.1,
136.0, 135.5, 128.6, 128.0, 126.4, 126.1, 114.6, 109.1, 107.5, 97.9, 44.8,
21.5, 12.6; IR (Ṽ, cm-1): 2962, 2893, 1728, 1597, 1350, 1195, 1126,
56.5, 56.3; IR (Ṽ, cm-1): 3056, 2993, 1728, 1604, 1504, 1257, 1188, 756;
+
+
HRMS (ESI-TOF) (m/z) calculated C18H14NO4
:
308.0917; found
941, 817; HRMS (ESI-TOF) (m/z) calculated C21H21N2O2 : 333.1598;
308.0913 [M + H]+.
found 333.1598 [M + H]+.
9-Fluoro-6H-chromeno[4,3-b]quinolin-6-one (3ag): White solid; yield:
54.6 mg (68%); mp: 244–245 °C (lit.[18] 242.3−243.0°C); 1H NMR (400
MHz, CDCl3) δ 9.18 (s, 1H), 8.76 (dd, J = 7.9, 1.6 Hz, 1 H), 8.26 (dd, J =
9.3, 5.2 Hz, 1H), 7.68 – 7.64 (m, 1H), 7.67 – 7.60 (m, 2H), 7.48 – 7.40
3-(Diethylamino)-11-methyl-6H-chromeno[4,3-b]quinolin-6-one (3bc):
Yellow solid; yield: 51.2 mg (72%); mp: 175–177 °C; H NMR (400 MHz,
1
CDCl3) δ 9.22 (s, 1H), 8.19 – 8.16 (m, 1H) , 7.93 (d, J = 8.5 Hz, 1H), 7.74
– 7.70 (m, 1H), 7.50 – 7.46 (m, 1H), 6.78 – 6.69 (m, 2H), 3.52 (q, J = 7.1
Hz, 4H), 2.87 (s, 3H), 1.31 (d, J = 7.1 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 160.0, 154.0, 150.6, 149.6, 147.7, 139.3, 136.0, 135.9, 132.6,
129.4, 128.6, 127.4, 125.6, 109.4, 100.0, 97.1, 45.1, 18.3, 12.5; IR (Ṽ,
cm-1): 2970, 2916, 1720, 1597, 1489, 1350, 1134, 779; HRMS (ESI-TOF)
(m/z) calculated C21H21N2O2+ : 333.1598; found 333.1554 [M + H]+.
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.5 (JC-F
= 85.3 Hz), 159.4,
152.6, 149.0 (JC-F = 2.7 Hz), 148.3, 140.2 (JC-F = 6.1 Hz), 132.4, 132.2
(JC-F = 8.9 Hz), 127.9, 127.8, 125.1 (JC-F = 3.3 Hz), 124.0 (JC-F = 26.2
Hz), 119.4, 117.4, 116.4, 112.0 (JC-F = 21.8 Hz); IR (Ṽ, cm-1): 3066, 2963,
1735, 1604, 1496, 1458, 1357, 1226, 1118, 864, 756; HRMS (ESI-TOF)
(m/z) calculated C16H9FNO2+ : 266.0612; found 266.0603 [M + H]+.
3-(Diethylamino)-9-methoxy-6H-chromeno[4,3-b]quinolin-6-one
(3be): Red solid; yield: 54.4 mg (73%); mp: 183–185 °C; 1H NMR (400
MHz, CDCl3) δ 9.11 (s, 1H), 8.60 (d, J = 8.9 Hz, 1 H), 8.18 (d, J = 9.3 Hz,
1H), 7.65 (dd, J = 9.2, 2.6 Hz, 1H), 7.29 (d, J = 2.4 Hz, 1H), 6.88 (dd, J =
8.9, 2.1 Hz, 1H), 6.70 (d, J = 2.0 Hz, 1H), 4.12 (s, 3H), 3.63 (q, J = 7.0
Hz, 4H), 1.43 (t, J = 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.4,
157.3, 154.3, 150.6, 148.6, 147.9, 138.9, 130.3, 127.2, 126.4, 125.8,
114.7, 109.0, 107.5, 105.8, 97.9, 55.6, 44.7, 12.6; IR (KBr, Ṽ, cm-1):
2970, 2938, 1712, 1620, 1597, 1496, 1411, 1342, 1234, 1126, 1010,
779; HRMS (ESI-TOF) (m/z) calculated C21H21N2O3+ : 349.1547; found
349.1542 [M + H]+.
9-Chloro-6H-chromeno[4,3-b]quinolin-6-one (3ah): White solid; yield:
58.7 mg (69%); mp: 240–242 °C (lit.[18] 245.7−246.4°C); 1H NMR (400
MHz, CDCl3) δ 9.13 (s, 1H), 8.75 (d, J = 6.9 Hz, 1H), 8.18 (d, J = 9.0 Hz,
1H), 8.00 (d, J = 1.5 Hz, 1H), 7.85 (dd, J = 9.0, 1.9 Hz, 1H), 7.63 (t, J =
7.0 Hz, 1H), 7.49 – 7.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 161.0,
152.7, 149.8, 149.4, 140.0, 134.3, 133.4, 132.7, 131.1, 127.8, 127.7,
125.2, 125.1, 119.3, 117.5, 116.5; IR (Ṽ, cm-1): 3065, 2918, 1735, 1604,
1481, 1458, 1303, 1195, 1080, 925, 756; HRMS (ESI-TOF) (m/z)
calculated C16H9ClNO2+ : 282.0316; found 282.0314 [M + H]+.
9-Bromo-6H-chromeno[4,3-b]quinolin-6-one (3ai): White solid; yield:
65.9 mg (66%); mp: 232–234 °C (lit.[18] 230.0−231.0°C); 1H NMR (400
MHz, CDCl3) δ 9.09 (s, 1H), 8.72 (d, J = 7.9 H z, 1H), 8.14 (d, J = 1.7 Hz,
1H), 8.08 (d, J = 9.0 Hz, 1H), 7.96 (dd, J = 9.1, 2.0 Hz, 1H), 7.66 – 7.59
(m, 1H), 7.47 – 7.36 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 160.9, 152.7,
149.9, 149.6, 139.9, 136.8, 132.7, 131.2, 131.1, 128.2, 125.2, 125.1,
121.5, 119.3, 117.5, 116.4; IR (Ṽ, cm-1): 3065, 2924, 1735, 1604, 1481,
1373, 1172, 987, 910, 756; HRMS (ESI-TOF) (m/z) calculated
C16H9BrNO2+ : 325.9811; found 325.9809 [M + H]+.
3-(Diethylamino)-9,10-dimethoxy-6H-chromeno[4,3-b]quinolin-6-one
(3bf): Red solid; yield: 62.9 mg (78%); mp: 192–194 °C; 1H NMR (400
MHz, CDCl3) δ 8.90 (s, 1H), 8.44 (d, J = 9.0 H z, 1H), 7.45 (s, 1H), 7.13
(s, 1H), 6.75 – 6.72 (m, 1H), 6.57 (d, J = 2.5 Hz, 1H), 4.13 (s, 3H), 4.06
(s, 3H), 3.46 (t, J = 7.1 Hz, 4H), 1.26 (t, J = 7.1 Hz, 6H); 13C NMR (100
MHz, CDCl3) δ 162.61, 155.7, 154.4, 150.7, 149.7, 138.0, 125.6, 122.2,
112.7, 109.0, 107.6, 107.3, 106.4, 106.0, 100.7, 98.0, 56.4, 56.2, 44.8,
12.6; IR (Ṽ, cm-1): 2970, 2940, 1712, 1620, 1597, 1496, 1342, 1126, 779;
+
HRMS (ESI-TOF) (m/z) calculated C22H23N2O4
379.1653 [M + H]+.
: 379.1652; found
6-Oxo-6H-chromeno[4,3-b]quinoline-9-carbonitrile (3aj): White solid;
yield: 8.24 mg (10%); mp: 229–231 °C; 1H NMR (400 MHz, CDCl3) δ 9.32
(s, 1H), 8.81 (d, J = 2.4 Hz, 1H), 8.46 (d, J = 1.6 Hz, 1H), 8.38 – 8.34 ( m,
1H), 8.06 (dd, J = 8.9, 1.8 Hz, 1H), 7.72 – 7.67 (m, 1H), 7.52 – 7.44 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 160.4, 153.2, 152.3, 151.7, 141.7,
135.5, 133.6, 133.4, 131.1, 126.5, 125.7, 125.3, 119.0, 117.8, 117.6,
3-(Diethylamino)-9-fluoro-6H-chromeno[4,3-b]quinolin-6-one (3bg):
1
Yellow solid; yield: 41.8 mg (58%); mp: 188–190 °C; H NMR (400 MHz,
CDCl3) δ 9.01 (s, 1H), 8.43 (d, J = 9.0 Hz, 1H), 8.11 (dd, J = 9.3, 5.2 Hz,
1H), 7.64–7.58 (m, 1H), 7.52 (dd, J = 8.4, 2.8 Hz, 1H), 6.71 (dd, J = 9.0,
2.5 Hz, 1H), 6.52 (d, J = 2.5 Hz, 1H), 3.47 (q, J = 7.1 Hz, 4H), 1.27 (t, J =
7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 161.5 (JC-F = 88.3 Hz), 158.6,
154.6, 151.1, 150.1 (JC-F = 2.3 Hz), 148.6, 140.0 (JC-F = 5.8 Hz), 131.4
(JC-F = 8.8 Hz), 126.6 (JC-F = 10.0 Hz), 126.1, 123.3 (JC-F = 25.9 Hz),
115.3, 112.0 (JC-F = 21.6 Hz), 109.1, 107.1, 97.9, 44.8, 12.5; IR (Ṽ, cm-1):
3062, 2970, 1735, 1604, 1527, 1489, 1350, 1257, 1195, 802 ; HRMS
117.3, 111.2; IR (Ṽ, cm-1): 2978, 2930, 2222, 1735, 1604, 1450, 1350,
+
1195, 1018, 817; HRMS (ESI-TOF) (m/z) calculated C17H9N2O2
273.0659; found 273.0620 [M + H]+.
:
3-(Diethylamino)-6H-chromeno[4,3-b]quinolin-6-one (3ba): Yellow
solid; yield: 46.4 mg (68%); mp: 170–172 °C; 1H NMR (400 MHz, CDCl3)
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801292
European Journal of Organic Chemistry
FULL PAPER
(ESI-TOF)(m/z) calculated C20H18FN2O2+ : 337.1347; found 337.1331 [M
= 8.4 Hz, 1H); 13C NMR (100 MHz, DMSO–d6) δ 160.5, 152.0, 150.3,
148.3, 141.5, 135.4, 134.5, 130.4, 129.3, 128.4, 127.8, 127.0, 121.8,
120.2, 117.3, 116.5; IR (Ṽ, cm-1): 2916, 2853, 1743, 1604, 1550,
1489,1373,1172, 995, 802; HRMS (ESI-TOF) (m/z) calculated
C16H9BrNO2+ : 325.9811; found 325.9810 [M + H]+.
+ H]+.
9-Chloro-3-(diethylamino)-6H-chromeno[4,3-b]quinolin-6-one (3bh):
1
Yellow solid; yield: 45.2 mg (60%); mp: 185–187 °C; H NMR (400 MHz,
CDCl3) δ 9.00 (s, 1H), 8.46 (d, J = 9.0 Hz, 1H), 8.06 (d, J = 9.1 Hz, 1H),
7.90 (d, J = 2.3 Hz, 1H), 7.76 (dd, J = 9.1, 2.4 Hz, 1H), 6.73 (dd, J = 9.0,
2.5 Hz, 1H), 6.54 (d, J = 2.5 Hz, 1H), 3.48 (q, J = 7.1 Hz, 4H), 1.27 (t, J =
7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 161.9, 154.7, 151.3, 150.9,
149.9, 139.9, 133.8, 131.6, 130.5, 127.7, 126.7, 126.2, 115.4, 109.2,
2-Bromo-9-methoxy-6H-chromeno[4,3-b]quinolin-6-one (3ce): White
solid; yield: 53.3 mg (72%); mp: 220–224 °C; 1H NMR (400 MHz, CDCl3)
δ 9.10 (s, 1H), 8.88 (d, J = 2.4 Hz, 1H), 8.17 (brs, 1H), 7.66 (dd, J = 8.7,
2.5 Hz, 1H), 7.61 (dd, J = 9.3, 2.8 Hz, 1H), 7.30 (s, 1H), 7.25 (d, J = 2.8
Hz, 1H), 4.01 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.0, 158.7, 151.2,
147.6, 146.2, 139.0, 134.4, 131.0, 128.8, 127.5, 127.4, 121.5, 119.1,
118.0, 115.7, 105.6, 55.8; IR (Ṽ, cm-1): 2954, 2924, 1735, 1620, 1597,
107.0, 97.9, 44.8, 12.5; IR (Ṽ, cm-1): 3062, 2970, 1728, 1597, 1442,
+
1350, 1126, 825; HRMS (ESI-TOF) (m/z) calculated C20H18ClN2O2
353.1051; found 353.1065 [M + H]+.
:
+
1234, 1180, 1026, 810; HRMS (ESI-TOF) (m/z) calculated C17H11BrNO3
: 355.9917; found 355.9911 [M + H]+.
9-Bromo-3-(diethylamino)-6H-chromeno[4,3-b]quinolin-6-one (3bi):
1
Yellow solid; yield: 49.2 mg (58%); mp: 184–186 °C; H NMR (400 MHz,
CDCl3) δ 8.95 (s, 1H), 8.42 (d, J = 9.0 Hz, 1H), 8.04 (d, J = 2.2 Hz, 1H),
7.96 (d, J = 9.1 Hz, 1H), 7.86 (dd, J = 9.1, 2.2 Hz, 1H), 6.71 (dd, J = 9.0,
2.5 Hz, 1H), 6.51 (d, J = 2.5 Hz, 1H), 3.47 (q, J = 7.1 Hz, 4H), 1.27 (t, J =
7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 161.8, 154.7, 151.3, 150.9,
150.0, 139.7, 136.2, 131.1, 130.5, 127.2, 126.3, 119.5, 115.3, 109.2,
106.9, 97.9, 44.8, 12.6; IR (Ṽ, cm-1): 2970, 2923, 1735, 1597, 1535,
1481, 1404, 1350, 1234, 1188, 1018, 941, 817; HRMS (ESI-TOF) (m/z)
calculated C20H18BrN2O2+ : 397.0546; found 397.0538 [M + H]+.
2-Bromo-9-chloro-6H-chromeno[4,3-b]quinolin-6-one (3ch): White
solid; yield: 48.9 mg (65 %); mp: 221–223 °C; 1H NMR (400 MHz, CDCl3
) δ 9.15 (s, 1H), 8.89 (d, J = 2.4 Hz, 1H), 8.21 (d, J = 9.1 Hz, 1H), 8.04 (d,
J = 2.3 Hz, 1H), 7.90 (dd, J = 9.1, 2.3 Hz, 1H), 7.71 (dd, J = 8.7, 2.5 Hz,
1H), 7.31 (d, J = 8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3 ) δ 160.4,
151.5, 149.4, 148.6, 140.2, 135.4, 134.7, 133.9, 131.2, 128.0, 127.9,
127.8, 121.0, 119.3, 118.2, 116.3; IR (Ṽ, cm-1): 2924, 2854, 1728, 1612,
1504, 1458, 1249, 1219, 1080, 833, 723; HRMS (ESI-TOF) (m/z)
calculated C16H8BrClNO2+ : 361.9400; found 361.9316 [M + H]+.
3-(Diethylamino)-6-oxo-6H-chromeno[4,3-b]quinoline-9-carbonitrile
(3bj): Yellow solid; yield: 5.88 mg (8%); mp: 191–193 °C; 1H NMR (400
MHz, CDCl3) δ 9.10 (s, 1H), 8.48 (d, J = 9.0 Hz, 1H), 8.31 (d, J = 1.8 Hz,
1H), 8.16 (d, J = 8.9 Hz, 1H), 7.93 (dd, J = 8.9, 1.9 Hz, 1H), 6.75 (dd, J =
9.1, 2.5 Hz, 1H), 6.55 (d, J = 2.5 Hz, 1H), 3.50 (q, J = 7.1 Hz, 4H), 1.29
(t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 161.3, 155.2, 153.0,
152.3, 152.0, 141.3, 135.5, 133.0, 130.2, 126.8, 125.4, 118.4, 116.1,
109.4, 109.2, 106.6, 97.8, 44.9, 12.5; IR (Ṽ, cm-1): 2978, 2930, 2222,
1735, 1604, 1450, 1396, 1234, 1018, 817; HRMS (ESI-TOF) (m/z)
calculated C21H18N3O2+ : 344.1394; found 344.1387 [M + H]+.
2-Bromo-9-bromo-6H-chromeno[4,3-b]quinolin-6-one (3ci): White
solid; yield: 47.0 mg (56%); mp: 232–234 °C; 1H NMR (400 MHz, CDCl3)
δ 9.17 (s, 1H), 8.92 (brs, 1H), 8.23 (d, J = 2.2 Hz, 1H), 8.16 (d, J = 9.1
Hz, 1H), 8.03 (dd, J = 9.1, 2.2 Hz, 1H), 7.73 (dd, J = 8.7, 2.4 Hz, 1H),
7.32 (d, J = 8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 160.9, 151.6,
149.6, 148.7, 142.3, 140.1, 137.1, 135.4, 131.2, 131.2, 128.5, 128.0,
122.0, 121.0, 119.3, 118.2, 116.3; IR (Ṽ, cm-1): 2916, 2847, 1743, 1651,
1543, 1265, 1172, 995, 825; HRMS (ESI-TOF) (m/z) calculated
C16H8Br2NO2+ : 403.8916; found 403.8906 [M + H]+.
3-(Diethylamino)-10-methyl-6H-chromeno[4,3-b]quinolin-6-one (3bk):
Yellow solid; yield: 52.7 mg (74%); mp: 182–184 °C; H NMR (400 MHz,
2-Methyl-6H-chromeno[4,3-b]quinolin-6-one (3da): White solid; yield:
51.5 mg (69%); mp: 231–233 °C; 1H NMR (400 MHz, CDCl3) δ 9.26 (s,
1H), 8.61 (s, 1H), 8.28 (d, J = 8.6 Hz, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.96
– 7.93 (m, 1H), 7.70 – 7.66 (m, 1H), 7.44 – 7.41 (m, 1H), 7.32 (d, J = 8.4
Hz, 1H), 2.55 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.5, 151.1, 150.9,
149.8, 141.2, 134.8, 133.4, 129.5, 129.5, 127.4, 127.3, 125.0, 119.2,
117.2, 115.9, 21.0; IR (Ṽ, cm-1): 2954, 2916, 1735, 1620, 1597, 1458,
1373, 1280, 1226, 1026, 825; HRMS (ESI-TOF) (m/z) calculated
C17H12NO2+ : 262.0863; found 262.0843 [M + H]+.
1
CDCl3) δ 9.02 (s, 1H), 8.47 (d, J = 9.0 Hz, 1H), 7.92 – 7.87 (m, 1H), 7.80
(d, J = 8.3 Hz, 1H), 7.35 (dd, J = 8.4, 1.5 Hz, 1H), 6.72 (dd, J = 9.0, 2.5
Hz, 1H), 6.54 (d, J = 2.5 Hz, 1H), 3.46 (q, J = 7.1 Hz, 4H), 2.60 (s,
3H),1.26 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.4, 154.7,
151.6, 151.0, 150.7, 144.1, 140.5, 129.0, 128.4, 127.8, 126.2, 124.5,
113.9, 109.0, 107.4, 97.9, 44.8, 22.3, 12.6; IR (Ṽ, cm-1): 2970, 2915,
1720, 1597, 1489, 1396, 1195, 879, 779; HRMS (ESI-TOF) (m/z)
calculated C21H21N2O2+ : 333.1598; found 333.1605 [M + H]+.
9-Methoxy-2-methyl-6H-chromeno[4,3-b]quinolin-6-one (3de): White
solid; yield: 61.1 mg (74%); mp: 237–239 °C; 1H NMR (400 MHz, CDCl3)
δ 9.07 (s, 1H), 8.54 – 8.48 (m, 1H), 8.13 (d, J = 9.3 Hz, 1H), 7.58 (dd, J =
9.3, 2.8 Hz, 1H), 7.37 (dd, J = 8.3, 1.8 Hz, 1H), 7.29 – 7.26 (m, 1H), 7.21
(d, J = 2.8 Hz, 1H), 4.00 (s, 3H), 2.52 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.7, 158.3, 150.4, 147.6, 147.5, 139.0, 134.6, 132.7, 130.8,
128.4, 127.0, 124.6, 119.3, 117.1, 116.0, 105.6, 55.8, 21.0; IR (Ṽ, cm-1):
2954, 2916, 1735, 1620, 1504, 1450, 1234, 1126, 1010, 833, 810; HRMS
(ESI-TOF) (m/z) calculated C18H14NO3+ : 292.0968; found 292.0948 [M +
H]+.
3-(Diethylamino)-9-isopropyl-6H-chromeno[4,3-b]quinolin-6-one
(3bl): Red solid; yield: 57.9 mg (75 %); mp: 180–182 °C; H NMR (400
1
MHz, CDCl3) δ 9.05 (s, 1H), 8.48 (d, J = 9.0 Hz, 1H), 8.06 (d, J = 8.8 Hz,
1H), 7.79 – 7.70 (m, 2H), 6.72 (dd, J = 9.0, 2.5 Hz, 1H), 6.55 (d, J = 2.5
Hz, 1H), 3.47 (q, J = 7.1 Hz, 4H), 1.39 (s, 3H), 1.38 (s, 3H), 1.28 (brs,
1H), 1.26 (t, J = 6.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 162.4, 154.6,
150.9, 150.5, 150.0, 146.7, 140.4, 133.2, 128.7, 126.4, 126.1, 125.3,
114.6, 109.0, 107.5, 97.9, 44.8, 34.0, 29.7, 23.7, 12.6; IR (Ṽ, cm-1): 2970,
2892, 1728, 1620, 1597, 1527, 1489, 1404, 1226, 1118, 1072, 879;
+
HRMS (ESI-TOF) (m/z) calculated C23H25N2O2
361.1908 [M + H]+.
: 361.1911; found
3,9-Dimethoxy-6H-chromeno[4,3-b]quinolin-6-one (3ee): White solid;
yield: 56.6 mg (71%); mp: 235–237 °C; 1H NMR (400 MHz, CDCl3) δ 9.08
(s, 1H), 8.65 (d, J = 8.8 Hz, 1H), 8.13 (d, J = 9.3 Hz, 1H), 7.58 (dd, J =
9.3, 2.8 Hz, 1H), 7.22 (d, J = 2.8 Hz, 1H), 7.01 (dd, J = 8.8, 2.5 Hz, 1H),
6.90 (d, J = 2.4 Hz, 1H), 4.00 (s, 3H), 3.94 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 162.8, 158.0, 153.7, 147.7, 147.6, 139.2, 130.6, 128.0, 127.1,
2-Bromo-6H-chromeno[4,3-b]quinolin-6-one (3ca): White solid; yield:
46.0 mg (68%); mp: 218– 220 °C; 1H NMR (400 MHz, DMSO–d6) δ 9.39
(s, 1H), 8.73 (brs, 1H), 8.35 (d, J = 8.2 Hz, 1H), 8.24 (d, J = 9.5 Hz, 1H),
8.10 – 8.04 (m, 1H), 7.89 – 7.83 (m, 1H), 7.82 – 7.77 (m, 1H), 7.47 (d, J
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126.0, 115.1, 112.8, 105.7, 101.4, 55.8, 55.8; IR (Ṽ, cm-1): 3080, 2994,
1735, 1627, 1496, 1458, 1381, 1234, 1157, 1126, 779; HRMS (ESI-TOF)
(m/z) calculated C18H14NO4+ : 308.0917; found 308.0893 [M + H]+.
Med. Chem. 2012, 20, 759-768; b) D. Kumar, P. Sharma, H. Singh, K.
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9-Fluoro-3-methoxy-6H-chromeno[4,3-b]quinolin-6-one (3eg): White
1
solid; yield: 44.5 mg (58%); mp: 239–241°C; H NMR (400 MHz, CDCl3)
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= 6.1 Hz), 131.8 (JC-F = 8.9 Hz), 127.3 (JC-F =
10.2 Hz), 126.28, 123.9 (JC-F = 26.1 Hz), 115.6, 112.9, 112.5 112.0 (JC-
F= 21.1 Hz), 101.5, 55.8; IR (Ṽ, cm-1): 2954, 2916, 1728, 1604, 1465,
1357, 1203, 1157, 1026, 941, 848; HRMS (ESI-TOF) (m/z) calculated
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1
7.9, 1.6 Hz, 1H), 8.29 (d, J = 8.6 Hz, 1H), 8.07 (d, J = 8.1 Hz, 1H), 8.09 –
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(EMR/2017/000598). SK thanks UGC, New Delhi, for providing a
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Keywords: Nitrogen heterocycles•Domino reactions
•Coumarin•Quinolinones•Cyclization
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Key Topic*
Santosh Kumari, S. M. Abdul Shakoor,
Datta Markad, Sanjay K. Mandal, Rajeev
Sakhuja*
Page No. – Page No.
NH4OAc-promoted Cascade
Approach towards Aberrant
Synthesis of Chromene-fused
Quinolinones
Metal-free strategy for chromene-fused quinolinones
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