Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and 1-aza-coumarins

Article abstract of DOI:10.1002/jhet.3090

A one pot three component, copper catalyzed azide-alkyne cycloaddition reaction has been employed for the synthesis of bis-coumarinyl triazoles (A–D) using 4-chloro, 4-bromomethyl, 3-bromoacetyl and 4-bromomethyl-1-aza-coumarins (I–IV), sodium azide, and coumarin propargyl ethers (V–IX) in moderate yields.

Full text of DOI:10.1002/jhet.3090

Month 2018
Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins
and 1-aza-coumarins
*
Hrishikesh M. Revankar and Manohar V. Kulkarni
Department of Studies in Chemistry, Karnatak University, Pavate Nagar, Dharwad 580003, India
*
E-mail: manohar274@gmail.com
Received May 3, 2015
DOI 10.1002/jhet.3090
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A one pot three component, copper catalyzed azide-alkyne cycloaddition reaction has been employed for
the synthesis of bis-coumarinyl triazoles (A–D) using 4-chloro, 4-bromomethyl, 3-bromoacetyl and
4-bromomethyl-1-aza-coumarins (I–IV), sodium azide, and coumarin propargyl ethers (V–IX) in moderate
yields.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
and montmorillonite KSF clay supported CuO
nanoparticles [5] have been developed. Direct arylation
that is, SNAr reactions have also been reported [6]. A
The azide alkyne cycloaddition was initially investigated
as a two component 1,3-dipolar cycloaddition and the use
of Cu(I) salts has resulted in the regioselective formation
of 1,4-substituted triazoles under the so-called click
chemistry conditions. In situ generation of azides using
suitable halides and sodium azide and their subsequent
reaction with acetylenic dipolarophiles in a single pot
makes this a three component reaction that was first
realized in practice by Appukutam et al. under
microwave conditions [1]. Since then, several different
variants such as in copper nanoparticles [2]
(CuBr(PPh3)3) [3], over copper(II) sulfate supported on
alumina (Cu/Al2O3) under ball-milling conditions [4],
one-pot,
three-step
Sonogashira
cross-coupling-
desilylation-cycloaddition sequence was developed for
the convenient preparation of 1,4-disubstituted 1,2,3-
triazoles [7]. A one pot multicomponent tandem copper-
catalyzed azidation and copper catalyzed azide-alkyne
cycloaddition reactions were developed to afford a library
of 1-20-thiazolyl-1,2,3-triazoles that were tested for their
anticancer activity [8]. One-pot synthesis of novel 1,2,3-
triazoles containing nitrogen, oxygen, and sulfur
functionalized arms has also been reported [9].
Halohydrin dehalogenase has been used to bring about
enantioselective azidolysis of aromatic epoxides to
© 2018 Wiley Periodicals, Inc.

H. M. Revankar and M. V. Kulkarni
Vol 000
1,2-azido alcohols that were subsequently ligated to alkynes
producing chiral hydroxyl triazoles in a one-pot procedure
with excellent enantiomeric excess [10]. The three-step,
one-pot protocol based on decarboxylative coupling of
alkynoic acids and 1,3-dipolar cycloaddition of azides
enables a highly efficient synthesis of a variety of
functionalized 1,2,3-triazoles [11]. A one-pot reaction for
Cu(II)-catalyzed diazo transfer and Cu(I)-catalyzed azide-
alkyne 1,3-dipolar cycloaddition have been reported to
yield 1,4-disubstituted 1,2,3-triazoles in excellent yields
from a variety of readily available amines without the need
for isolation of the azide intermediates [12]. Triazolyl
azido alcohols have been synthesized from terminal
alkyne via oxirane ring-opening of epichlorohydrin [13].
The present work is aimed at adding a new dimension to
the three component version of the azide alkyne
cycloaddition. The in situ generated azides have been
derived from heteroaryl halides, allyl halides, α-halo
ketones, and isosteric systems represented by 4-chloro
coumarins, 4-bromomethyl coumarins, 3-bromoacetyl
The in situ generation of azides was achieved by the
reaction of halides (I–IV) with sodium azide in aqueous
acetone at room temperature. After the completion of
reaction (15–20 min), the acetylenic dipolarophile was
added and the reaction was continued under click
chemistry conditions [18]. Completion of the reaction is
monitored by thin-layer chromatography (TLC) and usual
workup, purification, and crystallization resulted in a
series of pure triazoles (A–D).
RESULT AND DISCUSSION
The ipso-chloro displacement in the case of 4-chloro-
coumarins (I) was found to occur at room temperature in
aqueous acetone and the bis-coumarinyl triazole A
(Scheme 1) were obtained by its reaction with
dipolarophile (VI).
Formation of product A1 (R = 6–CH3) (Scheme 1) was
confirmed by spectral analysis. IR spectrum exhibited an
intense band at 1720 cmꢀ1, due to lactone carbonyl. It
was further confirmed by 1H–NMR, wherein the
characteristic peak for coumarin that is, C3─H proton for
triazole linked coumarin was observed as a singlet at
6.9 ppm. The C6─CH3 resonated at 2.3 ppm as singlet.
The C3─H from ether linked coumarin resonated referred
coumarins,
and
4-bromomethyl-1-aza-coumarins
(carbostyrils), respectively. Regioisomeric dipolarophiles
in the form of coumarinyl propargyl ethers have been
used in this reaction. The resulting molecular matrices
with rotatable bonds would provide the required
conformational flexibility for biological activity.
0
to here as C3 ─H proton resonated at 6.4 ppm as doublet
with a coupling constant of 1.2 Hz, due to allylic
0
CHEMISTRY
coupling with C4 ─CH3 that resonated at 2.4 ppm as
doublet with coupling constant of 1.2 Hz. The O─CH2
protons linking triazole to coumarin were observed at
5.4 ppm as singlet, the C5─H of triazole that resonates
downfield at 8.9 ppm confirms the formation of 1,4-
substituted triazoles. In 13C–NMR, the two lactone
carbons resonated at 160.8 and 160.0 ppm, respectively,
Heteroaryl halides employed in this work differ
significantly in their reactivity towards nucleophiles.
4-Chloro coumarins [14], 4-bromomethyl coumarins [15],
3-bromoacetyl coumarins [16], and 4-bromomethyl-
1-aza-coumarins(carbostyrils) [17] were synthesized in a
two/three step sequence according to literature methods.
Acetylenic dipolarophiles linked to hydroxy coumarins
via an ether linkage have been prepared by the reaction
of various hydroxy coumarins and propargyl bromides
[18–21] (Fig 1).
0
O─CH2 resonated at 61 ppm, C4 ─CH3 groups resonated
at 18 ppm while as C6─CH3 resonated at 20 ppm, and
remaining carbons resonated in the expected region
between 101 and 159 ppm. Molecular ion peak at m/z
415 in the EI-MS confirmed the proposed structure.
Figure 1. Coumarin linked acetylenic dipolarophiles employed in the three component one-pot reaction.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and
1-aza-coumarins
Scheme 1. Three component reaction of 4-chloro coumarins under click chemistry conditions.
The in situ allylic substitution was observed during the
reaction of 4-bromomethyl coumarins (II) with sodium
azide at room temperature that is similar to their reactivity
with substituted phenols [15]. Bis-coumarinyl triazoles B
(Scheme 2) with more number of rotatable C─C bonds
were generated by their reaction with dipolarophile VIII.
In a typical example B1 (R = 7,8–CH3), IR spectrum
exhibited an intense band at 1717 cmꢀ1, due to lactone
164 ppm. Molecular ion peak at m/z 429 in the EI-MS
confirmed the proposed structure.
3-Bromoacetyl coumarins III were employed as
model substrates for α-haloketones and the in situ
generated α-azido ketones were reacted with acetylenic
dipolarophile (V) to obtain regioisomeric bis-coumarinyl
triazoles ‘C’ (Scheme 3).
In a typical example C1 (R ═ H), IR spectrum exhibited
1
carbonyl. It was further confirmed by H–NMR, wherein
an intense band at 1716 cmꢀ1, due to lactone carbonyl. It
1
the characteristic peak for coumarin that is, C3─H proton
for triazole linked coumarin was observed as a singlet at
5.8 ppm. The –CH2 linking coumarin to triazoles
resonated at 6.0 ppm. The C3─H proton from ether
was further confirmed by H–NMR, the ─COCH2 linking
coumarin to triazoles resonated at 6.0 ppm. The C3─H
proton from ether linked coumarin resonated referred to
0
here as C3 ─H proton resonated at 6.2 ppm as doublet
0
linked coumarin resonated referred to here as C3 ─H
with a coupling constant of 1.2 Hz, due to allylic
coupling with C4─CH3 that resonated at 2.4 ppm as
doublet with coupling constant of 1.2 Hz. The O─CH2
protons linking triazole to coumarin were observed at
5.3 ppm as singlet, the C5─H of triazole that resonates
downfield at 8.8 ppm confirms the formation of 1,4-
substituted triazoles. The C4─H shows a characteristic
peak at 8.2 ppm. In 13C–NMR, the two lactone carbons
resonated at 161and 160 ppm, respectively. The ketonic
carbonyl group resonated at 189 ppm, O─CH2 resonated
at 61 ppm, N─CH2 resonated at 58 ppm, the methyl
carbon on coumarin resonated at 18 ppm, and remaining
proton resonated at 6.1 ppm. The O─CH2 protons linking
triazole to coumarin were observed at 5.4 ppm as singlet,
the C5─H of triazole that resonates downfield at 8.5 ppm
confirms the formation of 1,4-substituted triazoles. The
two methyl groups on coumarin resonated at 2.2 and
2.3 ppm, respectively. In 13C–NMR, the two lactone
carbons resonated at 164 and 161 ppm, respectively,
O─CH2 resonated at 62 ppm, N─CH2 resonated at
49 ppm, the two methyl carbon on coumarin resonated at
11 and 19 ppm, respectively, and remaining carbons
resonated in the expected region between 91 and
Scheme 2. One-pot synthesis of bis-coumarinyl triazoles by click chemistry.
Journal of Heterocyclic Chemistry
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H. M. Revankar and M. V. Kulkarni
Vol 000
Scheme 3. One-pot click reaction of 3-bromoacetyl coumarins.
carbons resonated in the expected region between 101 and
158 ppm. A peak at m/z 442 in the EI-MS corresponded to
the molecular ion.
between 109 and 161 ppm. Molecular ion peak at m/z
428 in the EI-MS confirmed the proposed structure.
Structural diversity of the halides, however, did not
affect the overall yield of the reactions significantly under
click chemistry conditions (Table 1). Yields of the
products A–D depended on the in situ generated azide.
However, the refluxing time for all the reactions was
around 8 h. It is pertinent to mention that the yields of
bis-coumarinyl triazoles in our earlier work by the
reaction of 4-azidomethyl coumarins were in the range
of 85–90% [22].
The
isosteric
4-bromomethyl-1-aza
coumarin
(carbostyril) IV similarly yielded triazoles ‘D’, the
structure of which was supported by spectral analysis.
Formation of product D1 (Scheme 4) was confirmed by
spectral analysis; IR spectrum exhibited an intense band at
1712 cmꢀ1, due to lactone carbonyl and at 1659 cmꢀ1, due
1
lactam carbonyl. It was further confirmed by H–NMR,
wherein the characteristic peak for coumarin that is,
C3─H proton for triazole linked coumarin was observed
as a singlet at 5.97 ppm. The ─CH2 linking coumarin to
triazoles resonated at 5.95 ppm. The C3─H proton from
ether linked coumarin resonated referred to here as
EXPERIMENTAL
0
C3 ─H proton resonated at 6.3 ppm as doublet with a
The melting points were determined by open capillary
method and are uncorrected. IR spectra (KBr disc) were
recorded on Nicolet ꢀ5700 FT-IR spectrometer. H NMR
coupling constant of 0.8 Hz, due to allylic coupling with
C4─CH3 that resonated at 2.40 ppm as doublet with
coupling constant of 0.8 Hz. The O─CH2 protons linking
triazole to coumarin were observed at 5.2 ppm as singlet,
the C5─H of triazole that resonates downfield at 8.3 ppm
confirms the formation of 1,4-substituted triazoles and
ring NH resonated at 10.9 ppm. In 13C–NMR, the lactone
carbons resonated at 160 ppm, O─CH2 resonated at
61 ppm, N─CH2 resonated at 49 ppm, the two methyl
carbon on coumarin resonated at 17 and 18 ppm, and
remaining carbons resonated in the expected region
1
spectra were recorded on Bruker 400 MHz Spectrometer
using DMSO-d6 as solvent and tetramethylsilane as
internal standard. The Chemical shifts are expressed in δ
ppm. Mass spectra were recorded using Shimadzu
GCMS-QP2010S. The elemental analysis was carried out
using Hereaus CHN rapid analyzer. The purity of the
compound was checked by TLC. All the chemicals
purchased were of analytical grade and were used
without further purification unless otherwise stated.
Scheme 4. One-pot SN-allylic 1,3-dipolar click reaction of 4-bromomethyl-1-aza-coumarin.
Journal of Heterocyclic Chemistry
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Month 2018
Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and
1-aza-coumarins
Table 1
(0.01 M) were added and the reaction was either stirred
Yields (isolated) for the triazoles A–D.
for 24 h or refluxed for 8 h on water bath. Reaction was
quenched in ice-water and neutralized with 1:1 HCl, the
precipitate obtained was then filtered and crystallized
from ethanol in 75% yield [18–21].
Compound
Yield (%)
Compound
Yield (%)
A1
A2
A3
A4
A5
B1
B2
B3
B4
B5
75
70
71
68
71
68
69
66
62
66
C1
C2
C3
C4
C5
D1
D2
D3
D4
D5
65
66
66
69
63
63
63
61
63
61
General method for synthesis of (A1–A5, B1–B5, and
C1–C5).
Substituted halocoumarin (I,II,III) (0.001 M)
and sodium azide (0.0012 M) (dissolved in water) and
substituted coumarin propargyl ethers (0.001 M) were
dissolved in 5 mL of acetone and the mixture was allowed
to stir for 15 min. To this, Na2CO3 (0.003 M) and ascorbic
acid (0.003 M) dissolved in 2.5 mL of water were added,
followed by CuSO4.5H2O (0.0015 M) dissolved in 2.5 mL
of water was added. It was allowed to stir for 15 min and
thereafter refluxed on water bath for 8 h. The reaction was
monitored by TLC. After completion, the reaction mixture
was cooled and the solid separated was filtered and
recrystallized from DMF to obtain pure compound.
Synthesis of substituted 4-chloro coumarins (I).
required 4-chlorocoumarin were synthesized by
chlorination of 4-hydroxy coumarin using POCl3 [14].
The
Synthesis of substituted 4-bromomethyl-coumarins (II).
All the required substituted 4-bromomethylcoumarin
[15] have been synthesized by the Pechmann
cyclization of various substituted phenols with
4-bromoethylacetoacetate.
4-Methyl-6-((1-(6-methyl-2-oxo-2H-chromen-4-yl)-1H-1,2,3-
triazol-4-yl)methoxy)-2H-chromen-2-one
(A1).
DMF,
mp–218–200°C; yield–75%; IR (KBr, cmꢀ1) v = 1730
(lactone C=O); 1H NMR (300 MHz, DMSO-d6),
0
δ(ppm) = 2.3 (s, 3H, ─CH3), 2.4 (d, 3H, C4 ─CH3,
Synthesis of substituted 3-bromoacetyl coumarins (General
0
J = 1.2 Hz), 5.4(s, 2H, O─CH2), 6.4 (d, 1H, C3 ─H,
method) (III).
The required 3-bromoacetylcoumarin is
synthesized by bromination of 3-acetyl coumarin in
chloroform [16].
J = 1.2 Hz), 6.9 (s, 1H, C3─H), 7.3–7.6 (m, 6H, Ar─H),
8.9 (s,1H, tri–H); 13C–NMR (100 MHz, DMSO-d6,
δppm) 18.1, 20.4, 61.2, 101.6, 110.8, 111.4, 112.6, 113.5,
114.0, 116.9, 124.7, 126.5, 126.7, 134.3, 134.4, 142.8,
145.8, 151.8, 153.3, 154.6, 159.5, 160.0, 160.8. EI-MS:
m/z–415 (M+., 3%); Anal. Calcd for C23H17N3O5 (%),
Calcd: C, 66.50; H, 4.12; N, 10.12; Found: C, 66.40; H,
4.10; N, 10.11.
Synthesis of substituted 4-bromomethyl-1-azacoumarins
(carbostyrils) (IV).
The required substituted 4-
bromomethylcarbostyril have been synthesized by
bromination of acetoacetanilides and cyclizing the
intermediate (2) in sulphuric acid to give 4-bromomethyl-
carbostyrils [17].
4-Methyl-7-((1-(2-oxo-2H-chromen-4-yl)-1H-1,2,3-triazol-4-
Synthesis of hydroxy-4-methyl coumarins. 7-Hydroxy-
4-methyl coumarin, 6-hydroxy-4-methyl coumarin, and
7,8-dihydroxy-4-methyl coumarin were prepared by the
Pechmann cyclization of the corresponding phenols with
ethyl acetoacetate according to the literature reports [18–21].
yl)methoxy)-2H–chromen-2-one (A2).
DMF, mp: 218–
220°C; yield–70%; IR (KBr, cm1),
v
=
1716
(lactone C=O); 1H NMR (400 MHz, DMSO-d6),
δ(ppm) = 2.4(d, 3H, ─CH3, J = 1.2 Hz), 5.4(s, 2H,
0
O─CH2), 6.2(d, 1H, C3 ─H, J = 1.2 Hz), 6.9 (s, 1H,
Synthesis of substituted 4-hydroxy coumarins.
Substituted 2-hydroxy acetophenone (2) (0.25 M) was
dissolved in excess of diethyl carbonate (50 mL),
followed by addition of excess of sodium metal (10 g),
upon which vigorous reaction occurs, this is then refluxed
on water bath for about 1 h and ethyl alcohol was added
to reaction mixture to remove remaining sodium. The
reaction mixture was quenched in water, if there is any
separation of non-aqueous layer, it is discarded. The
aqueous layer is separated out and acidified with 1:1 HCl
to obtain substituted 4-hydroxy coumarin, which was
then crystallized from ethanol in 60% yield [22].
C3─H), 7.0–7.8 (m, 7H, Ar─H), 8.9(s, 1H, tri-H);
13C–NMR (100 MHz, DMSO-d6, δppm) 18.1, 61.2,
101.6, 110.7, 111.3, 112.5, 113.5, 114.3, 117.1, 124.9,
125.3, 126.5, 126.6, 133.4, 142.8, 145.8, 153.3, 153.6,
154.6 159.3, 160.0, 160.8; EI-MS: m/z–401 (M+., 5%);
Anal. Calcd for C22H15N3O5 (%), Calcd: C, 65.83; H,
3.77; N, 10.47; Found: C, 65.73; H, 3.71; N, 10.40.
4-(4-((2-Oxo-2H-chromen-4-yloxy)methyl)-1H-1,2,3-triazol-
1-yl)-2H-chromen-2-one (A3).
DMF, mp–210–212°C;
1
yield–71%; IR (KBr, cmꢀ1), v = 1720 (lactone C=O); H
NMR (400 MHz, DMSO-d6), δ(ppm) = 5.6 (s, 2H,
0
O─CH2), 6.2 (s, 1H, C3 ─H), 7.0 (s, 1H, C3─H), 7.3–7.8
(m, 8H, Ar─H), 9.0 (s, 1H, tri-H); 13C–NMR (100 MHz,
DMSO-d6, δppm) 62.4, 91.5, 110.8, 114.3, 115.0, 116.4,
117.1, 123.0, 124.2, 125.0, 125.4, 126.8, 132.8, 133.4,
142.0, 145.8, 152.7, 153.6, 159.4, 161.4, 164.2; EI-MS:
Synthesis of coumarin propargyl ethers (V,VI,VII,VII,
IX).
Propargyl bromide (0.01 M) and anhydrous
K2CO3 (0.015 M) were taken in dry acetone and was
allowed to stir for 30 min. To this, hydroxyl coumarins
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H. M. Revankar and M. V. Kulkarni
Vol 000
m/zꢀ387 (M+., 3%); Anal. Calcd for C21H13N3O5 (%),
6-Chloro-4-((4-(((2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-
1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one (B3).
DMF,
Calcd: C, 65.12; H, 3.38; N, 10.85; Found: C, 65.11; H,
mp–293–295°C; yield–66%; IR (KBr, cmꢀ1), v = 1728
(lactone C=O); 1H NMR (400 MHz, DMSO-d6),
δ(ppm) = 5.4 (s, 2H, O─CH2), 5.9 (s, 1H, C3─H), 6.0
3.38; N, 10.81.
7-((1-(6-Chloro-2-oxo-2H-chromen-4-yl)-1H-1,2,3-triazol-4-
yl)methoxy)-8-hydroxy-4-methyl-2H-chromen-2-one (A4).
DMF, mp–248–250°C; yield–68%; IR (KBr, cmꢀ1),
0
(s, 2H, N─CH2), 6.1 (s, 1H, C3 ─H), 7.3–7.9 (m, 6H,
=
1732 (lactone C=O); 1H NMR (400 MHz,
Ar─H), 8.5 (s, 1H, tri-H) 13C–NMR (100 MHz,
DMSO-d6, δppm) 49.0, 62.6, 91.3, 115.0, 115.2, 116.4,
118.5, 118.8, 122.7, 124.1, 124.3, 126.3, 128.6, 132.2,
132.8, 141.7, 148.9, 151.7, 152.7, 158.8, 161.4, 164.2;
EI-MS: m/z–435(M+., 12%), 437 (M + 2+., 4%); Anal.
Calcd for C22H14ClN3O5 (%), Calcd: C, 60.63; H, 3.24;
v
DMSO-d6), δ(ppm) = 2.4 (d, 3H, ─CH3, J = 1.2 Hz), 5.4
0
(s, 2H, O─CH2), 6.4 (d, 1H, C3 ─H, J = 1.2 Hz),
6.9 (s, 1H, C3─H), 7.0–7.6 (m, 5H, Ar─H), 8.9 (s, 1H,
tri-H); 13C–NMR (100 MHz, DMSO-d6, δppm)
18.2, 61.4, 109.6, 111.4, 114.7, 115.6,117.6, 119.2, 119.8,
120.2,124.7, 126.4, 128.7, 133.0, 143.4, 144.5, 147.5,
152.3, 153.0, 154.1, 159.0, 159.8; EI-MS: m/z–451
(M+., 9%), 453 (M + 2+., 3%); Anal. Calcd for
C22H14ClN3O6 (%), Calcd: C, 58.48; H, 3.12; N, 9.30;
N, 9.64; Found: C, 60.61; H, 3.24; N, 9.60.
8-Hydroxy-7-((1-((7-methoxy-2-oxo-2H-chromen-4-yl)
methyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-methyl-2H-chromen-
2-one (B4). DMF, mp–242–244°C; yield–62%; IR (KBr,
cmꢀ1), v = 1707 (lactone C=O); 1H NMR (400 MHz,
DMSO-d6), δ(ppm) = 2.3 (d, 3H, ─CH3, J = 1.2 Hz), 3.8
(s, 3H, 7─OCH3), 5.3 (s, 2H, O─CH2), 5.1 (s, 1H,
Found: C, 58.41; H, 3.10; N, 9.25.
4-Methyl-6-((1-(2-oxo-2H-chromen-4-yl)-1H-1,2,3-triazol-4-
yl)methoxy)-2H-chromen-2-one (A5).
DMF, mp–222–
224°C; yield–71%; IR (KBr, cmꢀ1), v = 1720 (lactone
C=O); 1H NMR (300 MHz, DMSO-d6), δ(ppm) = 2.4
(d, 3H, ─CH3, J = 1.2 Hz), 5.4 (s, 2H, O─CH2), 6.3
0
C3─H), 5.9 (s, 2H, N─CH2), 6.2 (d, 1H, C3 ─H,
J = 1.2 Hz), 7.1–7.5 (m, 5H, Ar─H), 8.4 (s, 1H, tri-H);
EI-MS: m/z–461(M+.); Anal. Calcd for C24H19N3O7 (%),
Calcd: C, 62.47; H, 4.15; N, 9.11; Found: C, 62.41; H,
0
(d, 1H, C3 ─H, J = 1.2 Hz), 6.5 (s, 1H, C3─H), 7.2–7.8
(m, 7H, Ar─H), 8.8 (s, 1H, tri-H); EI-MS: m/zꢀ401 (M+.,
4.10; N, 9.10.
2%); Anal. Calcd for C22H15N3O5; (%), Calcd: C, 65.83;
4-((4-(((6-Chloro-2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-
1,2,3-triazol-1-yl)methyl)-2H-benzo[h]chromen-2-one (B5).
H, 3.77; N, 10.47; Found: C, 65.81; H, 3.67; N, 10.41.
7,8-Dimethyl-4-((4-(((2-oxo-2H-chromen-4-yl)oxy)methyl)-
1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one (B1).
DMF, mp–235–237°C; yield–66%; IR (KBr, cmꢀ1),
v
=
1716 (lactone C=O); 1H NMR (400 MHz,
DMF, mp–195–197°C; yield–68%; IR (KBr, cmꢀ1),
DMSO-d6), δ(ppm) = 5.3 (s, 2H, O─CH2), 5.8 (s, 1H,
v
=
1717 (lactone C=O); 1H NMR (400 MHz,
0
C3─H), 6.0 (s, 2H, N─CH2), 6.3 (s, 1H, C3 ─H), 7.1–7.9
(m, 9H, Ar─H), 8.4 (s, 1H, tri-H); EI-MS: m/z–485(M+.,
9%), 487 (M + 2+., 3%); Anal. Calcd for C26H16ClN3O5
(%), Calcd: C, 64.27; H, 3.32; N, 8.65; Found: C, 64.23;
H, 3.31; N, 8.65.
DMSO-d6), δ(ppm) = 2.2 (s, 3H, ─CH3), 2.3 (s, 3H,
─CH3), 5.4 (s, 2H, O─CH2), 5.8 (s, 1H, C3─H), 6.0
0
(s, 2H, N─CH2), 6.1 (s, 1H, C3 ─H), 7.2–7.7 (m, 6H,
Ar─H), 8.5 (s, 1H, tri-H); 13C–NMR (100 MHz,
DMSO-d6, δppm): 11.1, 19.8, 49.3, 62.6, 91.3, 112.6,
114.7, 115.0, 116.4, 121.4, 122.7, 124.0, 124.1, 125.7,
126.3, 132.7, 141.5, 142.0, 150.1, 151.2, 152.7, 159.5,
161.4, 164.2; EI-MS: m/zꢀ429 (M+., 5%); Anal. Calcd
for C24H19N3O5 (%), Calcd: C, 67.13; H, 4.46; N, 9.79;
4-Methyl-7-((1-(2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl)-1H-
1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (C1).
DMF,
mp–220–222°C; yield–65%; IR (KBr, cmꢀ1), v = 1716
1
(C=O); H NMR (400 MHz, DMSO-d6), δ(ppm) = 2.4
(d, 3H, ─CH3), 5.3 (s, 2H, O─CH2), 6.0 (s, 2H,
0
Found: C, 67.10; H, 4.41; N, 9.72.
5,7-Dimethyl-4-((4-(((4-methyl-2-oxo-2H-chromen-6-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl)methyl)-2H-chromen-2-one
N─CH2), 6.2 (d, 1H, C3 ─H), 7.0–8.0 (m, 7H, Ar─H),
8.2 (s, 1H, C4─H) 8.8 (s, 1H, tri-H); 13C–NMR
(100 MHz, DMSO d6, δppm) 18.0, 58.2, 61.5, 101.5,
111.2, 112.6, 113.3, 116.6, 116.8, 117.9, 122.0, 125.1,
126.4, 131.1, 135.2, 148.5, 153.3, 154.6, 154.6, 158.5,
160.0, 161.0, 189.3; EI-MS: m/zꢀ443 (1%, M+.); Anal.
Calcd for C24H17N3O6 (%), Calcd: C, 65.01; H, 3.86; N,
(B2).
DMF, mp–201–203°C; yield–69%; IR (KBr,
cmꢀ1), v = 1716 (lactone C=O); 1H NMR (400 MHz,
DMSO-d6), δ(ppm) = 2.3 (s, 3H, ─CH3), 2.4 (d, 3H,
─CH3, J = 1.2 Hz), 2.6 (s, 3H, ─CH3), 5.3 (s, 2H,
O─CH2), 5.1 (s, 1H, C3─H), 6.1 (s, 2H, N─CH2), 6.4
9.48; Found: C, 65.01; H, 3.80; N, 9.41.
0
(d, 1H, C3 ─H, J = 1.2 Hz), 7.0–7.3 (m, 6H, Ar─H), 8.3
8-Hydroxy-7-((1-(2-(8-methoxy-2-oxo-2H-chromen-3-yl)-2-
oxoethyl)-1H-1,2,3-triazol-4-yl)methoxy)-4-methyl-2H-
chromen-2-one (C2). DMF, mp–223–225°C; yield–66%;
(s, 1H, tri-H); 13C–NMR (100 MHz, DMSO d6, δppm)
18.1, 20.6, 23.3, 52.2, 62.6, 109.6, 112.6, 114.7, 115.0,
116.4, 121.4, 122.7, 124.1, 124.7, 125.7, 126.3, 132.7,
141.5, 142.0, 150.1, 151.2, 152.7, 159.5, 159.7, 161.2;
EI-MS: m/zꢀ443 (M+., 7%); Anal. Calcd for
C25H21N3O5 (%), Calcd: C, 67.71; H, 4.77; N, 9.48;
Found: C, 67.69; H, 4.72; N, 9.41.
1
IR (KBr, cmꢀ1), v = 1724 (C=O); H NMR (400 MHz,
DMSO-d6), δ(ppm) = 2.4 (d, 3H, ─CH3), 3.6 (s, 3H,
─OCH3), 5.2 (s, 2H, O─CH2), 5.9 (s, 2H, N─CH2), 6.2
0
(d, 1H, C3 ─H), 7.3–7.8 (m, 5H, Ar─H), 8.3 (s, 1H,
C4─H) 8.8 (s, 1H, tri-H); EI-MS: m/zꢀ489(M+.); Anal.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Cu (I) Catalyzed One Pot SN-Click Reactions of Halogenated Coumarins and
1-aza-coumarins
Calcd for C25H19N3O8 (%), Calcd: C, 61.35; H, 3.91; N,
8.59; Found: C, 61.31; H, 3.90; N, 8.53.
6-Bromo-3-(2-(4-(((4-methyl-2-oxo-2H-chromen-6-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl)acetyl)-2H–chromen-2-one
109.6, 114.6, 117.0, 117.4, 119.7, 120.1, 121.6, 121.8,
124.0, 125.5, 132.1, 137.2, 142.8, 145.7, 147.4, 152.9,
154.1, 159.8, 161.4; EI-MS: m/z–428 (M+., 2%); Anal.
Calcd for C24H20N4O4 (%), Calcd: C, 67.28; H, 4.71; N,
13.08; Found: C, 67.21; H, 4.70; N, 13.02.
(C3).
DMF, mp–190–192°C; yield–66%; IR (KBr,
1714 (C=O); 1H NMR (400 MHz,
cmꢀ1),
v =
4-((4-(((4-Methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-1H-
DMSO-d6), δ(ppm) = 2.4 (d, 3H, ─CH3), 5.2 (s, 2H,
1,2,3-triazol-1-yl)methyl)quinolin-2(1H)-one (D2).
DMF,
mp–242–244°C; yield–63%; IR (KBr, cmꢀ1), v = 1722
(lactone C=O); v = 1665 (amide C=O); 1H NMR
(400 MHz, DMSO-d6), δ(ppm) = 2.3 (d, 3H, ─CH3,
J = 1.2 Hz), 5.2 (s, 2H, O─CH2), 5.95 (s, 2H, N─CH2),
0
O─CH2), 5.9 (s, 2H, N─CH2), 6.2 (d, 1H, C3 ─H),
7.3–8.0 (m, 6H, Ar─H), 8.2 (s, 1H, C4─H) 8.8 (s, 1H,
tri-H); EI-MS: m/z–521(M+., 2%), 523 (M + 2+., 2%);
Anal. Calcd for C24H16BrN3O6 (%), Calcd: C, 55.19; H,
3.09; N, 8.05; Found: C, 55.12; H, 3.00; N, 8.05.
0
5.98 (s, 1H, C3─H), 6.2 (s, 1H, C3 ─H, J = 1.2 Hz),
4-((1-(2-Oxo-2-(2-oxo-2H-chromen-3-yl)ethyl)-1H-1,2,3-
7.0–7.8 (m, 7H, Ar─H), 8.3 (s, 1H, tri-H), 11.8 (s, 1H,
NH); 13C–NMR (100 MHz, DMSO-d6, δppm); 18.0, 49.6,
61.5, 101.6, 111.2, 112.5, 113.3, 115.7, 118.2, 120.4,
121.9, 122.5, 123.9, 16.4, 17.5, 129.0, 130.0, 138.9,
142.4, 145.2, 154.5, 160.9, 161.1; EI-MS: m/zꢀ414 (M+.,
4%); Anal. Calcd for C23H18N4O4 (%), Calcd: C, 66.66;
H, 4.38; N, 13.52; Found: C, 66.60; H, 4.31; N, 13.51.
6-Chloro-4-((4-(((8-hydroxy-4-methyl-2-oxo-2H-chromen-7-
yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)methyl)quinolin-2(1H)-one
triazol-4-yl)methoxy)-2H-chromen-2-one
(C4).
DMF,
mp–198–200°C; yield–69%; IR (KBr, cmꢀ1), v = 1714
1
(C=O); H NMR (400 MHz, DMSO-d6), δ(ppm) = 5.5
(s, 2H, O─CH2), 6.0 (s, 2H, N─CH2), 6.2 (d, 1H,
0
C3 ─H), 7.4–8.0 (m, 8H, Ar─H), 8.2 (s, 1H, C4─H) 8.8
(s, 1H, tri-H); EI-MS: m/zꢀ429(M+.); Anal. Calcd for
C23H15N3O6 (%), Calcd: C, 64.34; H, 3.52; N, 9.79;
Found: C, 64.30; H, 3.51; N, 9.75.
6-Chloro-4-((1-(2-oxo-2-(2-oxo-2H-chromen-3-yl)ethyl)-1H-
(D3).
DMF, mp–228–230°C; yield–61%; IR (KBr,
cmꢀ1), v = 1727 (lactone C=O); v = 1666 (amide C=O);
1H NMR (400 MHz, DMSO-d6), δ(ppm) = 2.3 (d, 3H,
─CH3, J = 1.2 Hz), 5.3 (s, 2H, O─CH2), 6.0 (s, 2H,
1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (C5).
DMF,
mp–220–222°C; yield–63%; IR (KBr, cmꢀ1), v = 1724
1
(C=O); H NMR (400 MHz, DMSO-d6), δ(ppm) = 5.4
0
(s, 2H, O─CH2), 6.0 (s, 2H, N─CH2), 6.2 (d, 1H, C3 ─H),
0
N─CH2), 6.2 (s, 1H, C3─H), 6.4 (s, 1H, C3 ─H,
7.3–8.0 (m, 7H, Ar─H), 8.1 (s, 1H, C4─H) 8.8 (s, 1H,
tri-H); EI-MS: m/z–463 (M+., 3%), 465 (M + 2+., 1%);
Anal. Calcd for C23H14ClN3O6 (%), Calcd: C, 59.56; H,
3.04; N, 9.06; Found: C, 59.52; H, 3.04; N, 9.06.
J = 1.2 Hz), 7.2–7.6 (m, 5H, Ar─H), 8.5 (s, 1H, tri-H),
11.5 (s, 1H, NH); EI-MS: m/zꢀ464(M+., 3%), 466
(M + 2+., 1%); Anal. Calcd for C23H17ClN4O5 (%),
Calcd: C, 59.43; H, 3.69; N, 12.05; Found: C, 59.40; H,
3.60; N, 12.00.
General method for synthesis of (D1–D5). Substituted
4-bromomethyl carbostyrils (IV) (0.001 M) and sodium
azide (0.0012 M) (dissolved in water) and substituted
coumarin propargyl ethers (0.001 M) were dissolved in
5 mL of DMF and the mixture was allowed to stir for
15 min. To this, Na2CO3 (0.003 M) and ascorbic acid
(0.003 M) dissolved in 2.5 mL of water were added,
followed by CuSO4.5H2O (0.0015 M) dissolved in
2.5 mL of water was added, upon which the reaction
mixture turned yellow. It was allowed to stir for another
15 min, thereafter, it was refluxed on water bath for 8 h.
The reaction was monitored by TLC. The reaction
mixture was cooled and the solid separated was filtered
off and was crystallized from DMF to obtain pure
7-Chloro-4-((4-(((2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-
1,2,3-triazol-1-yl)methyl)quinolin-2(1H)-one (D4).
DMF,
mp–268–270°C; yield–63%; IR (KBr, cmꢀ1), v = 1715
(lactone C=O); v = 1662 (amide C=O); 1H NMR
(400 MHz, DMSO-d6), δ(ppm) = 5.4 (s, 2H, O─CH2),
5.9 (s, 2H, N─CH2), 6.0 (s, 1H, C3─H), 6.1 (s, 1H,
0
C3 ─H), 7.2–7.8 (m, 7H, Ar─H), 8.5 (s, 1H, tri-H), 11.9
(s, 1H, NH); 13C–NMR (100 MHz, DMSO-d6, δppm);
49.6, 62.6, 91.3, 114.9, 115.9, 116.4, 120.9, 122.0, 122.8,
124.2, 126.0, 126.1, 132.8, 135.3, 139.9, 141.5, 144.9,
152.7, 161.0, 161.4, 161.2; EI-MS: m/zꢀ434 (M+., 15%),
436 (M + 2+., 5%); Anal. Calcd for C22H15ClN4O4 (%),
Calcd: C, 60.77; H, 3.48; N, 12.88; found: C, 60.71; H,
3.42; N, 12.83.
compound.
4-((4-(((6-Chloro-2-oxo-2H-chromen-4-yl)oxy)methyl)-1H-
8-Methyl-4-((4-(((4-methyl-2-oxo-2H-chromen-6-yl)oxy)
methyl)-1H-1,2,3-triazol-1-yl)methyl)quinolin-2(1H)-one
1,2,3-triazol-1-yl)methyl)quinolin-2(1H)-one (D5).
DMF,
(D1).
DMF, mp–262–264°C; yield–63%; IR (KBr,
mp–293–295°C; yield–61%; IR (KBr, cmꢀ1), v = 1718
(lactone C=O); v = 1660 (amide C=O); 1H NMR
(400 MHz, DMSO-d6), δ(ppm) = 5.3 (s, 2H, O─CH2), 5.9
cmꢀ1), v = 1712 (lactone C=O); v =1659 (amide C=O);
1H NMR (400 MHz, DMSO-d6), δ(ppm) = 2.40 (d, 3H,
─CH3, J = 0.8 Hz), 2.42 (s, 3H, ─CH3), 5.2 (s, 2H,
O─CH2), 5.95 (s, 2H, N─CH2), 5.97 (s, 1H, C3─H), 6.3
0
(s, 2H, N─CH2), 6.0 (s, 1H, C3─H), 6.4 (s, 1H, C3 ─H),
7.2–7.8 (m, 7H, Ar─H), 8.3 (s, 1H, tri-H), 11.9 (s, 1H,
NH); EI-MS: m/zꢀ434 (M+., 3%), 436 (M + 2+., 1%);
Anal. Calcd for C22H15ClN4O4 (%), Calcd: C, 60.77; H,
3.48; N, 12.88; Found: C, 60.71; H, 3.44; N, 12.88.
0
(s, 1H, C3 ─H, J = 0.8 Hz), 7.0–7.6 (m, 6H, Ar─H), 8.3
(s, 1H, tri-H), 10.9 (s, 1H, NH); 13C–NMR
(100 MHz, DMSO-d6, δppm); 17.1, 18.1, 49.9, 61.6,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

H. M. Revankar and M. V. Kulkarni
Vol 000
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a simpler method for
construction of triazoles in moderate yields which is
lesser than that observed in the reaction of azides and
alkynes.
Acknowledwgments. One of the authors Hrishikesh M.
Revankar acknowledges UGC for providing RFSMS
scholarship. The authors thank NMR Research Center, Indian
Institute of Science (IISc), Bangalore, and University
Sophisticated Instrumentation Center (USIC)-K.U. Dharwad for
spectral analysis.
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Additional Supporting Information may be found online
in the supporting information tab for this article.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet