Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl) propyloxy]-3-alkyl-4-methylcoumarins

Article abstract of DOI:10.1002/jhet.1917

A series of 50 novel 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-alkyl-4-methylcoumarins had been designed and synthesized in good to excellent yields via Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction "click chemistry" of 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarins with variety of acetylene derivatives. In turn, the precursor compound, that is, 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarin, was synthesized by condensation of epichlorohydrin with 7-hydroxy-3-alkyl-4-methylcoumarins followed by opening of the epoxide ring in the resulted 7-epoxymethoxy-3-alkyl-4-methylcoumarins with sodium azide. All the synthesized compounds were unambiguously identified on the basis of their spectral data analyses (IR, 1H-NMR, 13C-NMR spectra, and HRMS).

Full text of DOI:10.1002/jhet.1917

Month 2014 Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)
propyloxy]-3-alkyl-4-methylcoumarins
a
a
a
a
b
b
c
c
Anu Arya, Vinod Kumar, Divya Mathur, Sukhdev Singh, Raju Brahma, Rajpal Singh, Seema Singh, G. L. Sharma,
a
a
Virinder S. Parmar, and Ashok K. Prasad *
a
Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi 110 007, India
b
CFEES, Brig. S. K, Mazumdar Road, Timarpur, Delhi 110 054, India
c
IGIB, Delhi University Campus, Mall Road, Delhi 110 007, India
*
E-mail: ashokenzyme@yahoo.com
Received October 13, 2012
DOI 10.1002/jhet.1917
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A series of 50 novel 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-alkyl-4-methylcoumarins had been
designed and synthesized in good to excellent yields via Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction
“click chemistry” of 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarins with variety of acetylene
derivatives. In turn, the precursor compound, that is, 7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarin,
was synthesized by condensation of epichlorohydrin with 7-hydroxy-3-alkyl-4-methylcoumarins followed by
opening of the epoxide ring in the resulted 7-epoxymethoxy-3-alkyl-4-methylcoumarins with sodium azide.
All the synthesized compounds were unambiguously identified on the basis of their spectral data analyses
1
13
(
IR, H-NMR, C-NMR spectra, and HRMS).
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
small library of triazole-conjugated coumarins, that is,
7
-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-alkyl-4-
Click chemistry has been one of the most advanced
approaches for chemical transformation in combinatorial
and bioconjugation chemistry. It offers a unique method
for the synthesis of 1,2,3-triazole-containing molecules
methylcoumarins via Cu(I)-catalyzed 1,3-dipolar cycload-
dition reaction of corresponding azidocoumarin derivatives
with different alkynes.
[
1]. The compounds with 1,4-disubstituted 1,2,3-triazole
RESULTS AND DISCUSSION
moieties are known to display broad spectrum of chemother-
apeutic properties such as antimalarial [2], anticonvulsant
[
[
kingdom and have evoked a great deal of interest in recent
years because of their diverse pharmacological properties
A series of 50 novel 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)
propyloxy]-3-ethyl-/hexyl-4-methylcoumarins 11a–d, 12a–d,
15a–u, and 16a–u were synthesized via Cu(I)-catalyzed
click reaction of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-
4-methylcoumarin (8) and 7-(3-azido-2-hydroxypropyloxy)-
3-hexyl-4-methylcoumarins (9) with various alkynes 10a–d
and 14a–u in 80 to 92% yields. In turn, the synthesis of 7-
(3-azido-2-hydroxypropyloxy)-3-ethyl-/hexyl-4-methylcoumarins
8 and 9 were accomplished using a multistep process,
starting with the condensation of ethyl 2-ethylacetoacetate
3], antibacterial [4], antifungal [5], and anti-HIV agents
6]. Further, coumarins are broadly distributed in the plant
[
7]. They have shown to be useful as antioxidant [8],
inhibitors of platelet aggregation [9], anti-inflammatory
10], anticonvulsant [11], antiviral [12], anti-HIV [13],
[
anticoagulant [14], antibacterial [15], antitubercular [16],
and antifungal [17]. Herein, we report synthesis of a
©
2014 HeteroCorporation

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
Scheme 2. Alkylation of ethyl acetoacetate.
(
2) and ethyl 2-hexylacetoacetate (3) with resorcinol (1)
to afford 3-ethyl-7-hydroxy-4-methylcoumarin (4) and
-hexyl-7-hydroxy-4-methylcoumarin (5) in 80 and 78%
yields (Scheme 1). Ethyl 2-ethylacetoacetate/hexylacetoacetate
/3 was synthesized by alkylation at C-2 of ethyl acetoacetate
3
2
with ethyl bromide or n-hexyl bromide in THF in the presence
of NaH (Scheme 2). The epoximethylation of C-7 hydroxyl
group in 3-alkylcoumarins 4 and 5 using epichlorohydrin
in the presence of base afforded 7-epoxymethoxy-3-ethyl-
were achieved by the similar condensation reaction of
7-(3-azido-2-hydroxypropyloxy)-3-ethyl-/hexyl-4-methylcou-
marins 8 and 9 with propargyl aryl ethers 14a–u, which were in
turn prepared in excellent yields by heating substituted
phenols 13a–u with propargyl bromide in acetone in the pre-
4
-methylcoumarins (6) and 7-epoxymethoxy-3-hexyl-4-
methylcoumarins (7) in 72 and 70% yields. The opening
of epoxide ring in coumarins 6 and 7 with sodium azide
afforded the desired precursor, that is, azidocoumarins
8
and 9 in 90 and 85% yields (Scheme 1).
sence of anhydrous K CO in 90 to 95% yields (Scheme 4).
2 3
Traditionally, the triazole forming 1,3-dipolar cycloaddi-
Thus, a series of 50 triazole-conjugated coumarins, 7-[2-
hydroxy-3-(1,2,3-triazole-1-yl)propyloxy]-3-ethyl-/hexyl-4-
methylcoumarins 11a–d, 12a–d, 15a–u, and 16a–u, have
been synthesized together with their precursor coumarins 4
to 9. The structures of synthesized coumarin derivatives 4
to 9, 11a–d, 12a–d, 15a–u, and 16a–u were unambiguously
established on the basis of their spectral data analyses
( H-NMR, C-NMR, IR, and HRMS spectra). The structure
of known coumarins 4 and 5 were further confirmed by
comparison of their physical and spectral data with those
reported in the literature [20].
tion reaction between azide and alkyne is performed at high
temperature and for long duration that usually results in a
mixture of two isomers 1,4-disubstituted and 1,5-disubstituted
,2,3-triazoles [18]. Sharpless–Meldal 1,3-dipolar cycload-
dition reaction to form regioselectively 1,4-disubstituted
,2,3-triazole bridges is a very popular and useful reaction
for the bioconjugation [1a,19]. The reaction is regioselective
only in the presence of Cu(I) salts as a catalyst, because Cu(I)
as a catalyst strongly activate the terminal acetylenes toward
,3-dipole in azide to give the desired 1,4-disubstituted
,2,3-triazole. Thus, Cu(I)-catalyzed 1,3-dipolar cycloaddition
1
1
1
13
1
1
reaction of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-/hexyl-
-methylcoumarins 8 and 9 with commercially available
alkynes, such as phenyl acetylene (10a), pent-4-ynoic acid
EXPERIMENTAL
4
Melting points were determined on Buchi M-560 instrument
(Flawil, Switzerland) and are uncorrected. The IR spectra were
recorded on a Perkin-Elmer model 2000 FTIR spectrometer
(
(
10b), 5-chloro-1-pentyne (10c), and propargyl alcohol
10d), in the presence of catalytic amount of copper
(
Waltham, MA) by making KBr disc for solid samples and thin
sulfate–sodium ascorbate in t-BuOH/H O/THF (1:1:1)
2
1
13
film for oils. The H-NMR and C-NMR spectra were recorded
afforded 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-
ethyl-/hexyl-4-methylcoumarins 11a–d and 12a–d in 80
to 92% yields (Scheme 3).
The synthesis of 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propy-
loxy]-3-ethyl-/hexyl-4-methylcoumarins 15a–u and 16a–u
on a JEOL alpha-400 spectrometer (Tokyo, Japan) at 400 and
00.6 MHz, respectively, using TMS as an internal standard. The
1
chemical shift values are on d scale, and the coupling constants
1
(J) are in Hz. Signals due to OH group in H-NMR spectra recorded
in CDCl were verified by removing them by using D O exchange
3 2
Scheme 1. Synthesis of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-/hexyl-methylcoumarins.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
Scheme 3. Synthesis of 7-[2-hydroxy-3(1,2,3-triazol-1-yl)propyloxy]-3-ethyl-/hexyl-4-methylcoumarin.
Scheme 4. Synthesis of 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-ethyl-/hexyl-4-methylcoumarin.
ꢀ
method. The mass spectra were recorded on microTOF-Q instrument
from Bruker Daltonics, Bremen, Germany, and were run in ESI
positive mode. Reactions were conducted under an atmosphere of
nitrogen when anhydrous solvents were used. Analytical TLCs were
performed on precoated Merck silica gel (Prabhadevi, Mumbai, India)
added sodium hydride (130.6 mmol) in small lots at 0 C. The
ꢀ
reaction mixture was heated at 60 C for 2 h after the addition of
sodium hydride was completed. The contents of the reaction
flask were cooled to 0 C, and then addition of ethyl bromide or
1-bromohexane (80 mmol) dissolved in THF was carried out.
ꢀ
ꢀ
60F254 plates; the spots were detected under UV light. Silica gel
The resultant mixture thus obtained was heated at 100 C for
(
100–200 mesh) (S d fine-Chem Limited, Mumbai, India; Sigma-
10–12 h. The reaction was monitored by TLC (10% ethyl
acetate–petroleum ether). On completion of the reaction, as
indicated by TLC examination, unreacted sodium hydride was
deactivated by addition of ethyl acetate, and the solution was
then filtered to remove sodium bromide formed during
the reaction. The solution was washed with water, the organic
layer dried over anhydrous sodium sulfate, and the solvent
Aldrich, New Delhi, India) was used for column chromatography.
Chemicals were obtained from commercial suppliers and were used
without any further purification unless otherwise noted.
General procedure for the synthesis of ethyl 2-
ethylacetoacetate/hexylacetoacetate 2 and 3.
solution of ethyl acetoacetate (76.8 mmol) in THF (30 mL) was
To a stirred
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
evaporated. The crude product thus obtained was subjected to
column chromatography using silica gel (100–200 mesh), and
the desired products, that is, ethyl 2-ethylacetoacetate 2 or
ethyl 2-hexylacetoacetate 3, were eluted with 2% ethyl
acetate–petroleum ether as viscous oils. The structures of
compounds 2 and 3 were unambiguously established on the
basis of their spectral data analysis (IR, H-NMR, C-NMR
spectra, and HRMS) and their comparison with those reported
in the literature.[20]
(100.6 MH , CDCl ): d 14.03 (─(CH ) CH ), 14.79 (C-4 CH ),
Z 3 2 5 3 3
22.57 (─CH (CH ) CH CH ), 27.47 (─CH CH (CH ) CH ), 29.31
2
2 3
2
3
2
2
2 2
3
(─(CH
(─CH
2
)
2
CH
2
(CH
2
)
2
CH
3
), 31.63 (─(CH
2 3 2 2 3
) CH CH CH ), 53.26
2
of epoxide), 68.97 (─OCH
2
), 69.35 (─CH of epoxide),
101.28 (C-8), 112.03 (C-6), 114.76 (C-10), 124.06 (C-3), 125.47
(C-5), 145.98 (C-9), 153.36 (C-4), 160.03 (C-7), 162.07 (CO);
1
13
+
HR-ESI-TOF-MS m/z 317.1743 ([M + H] ), calcd for
+
[C19H O
24 4
+H] 317.1747.
Synthesis of 7-(3-azido-2-hydroxypropyloxy)-3-ethyl-
/hexyl-4-methylcoumarin (8 and 9). Epoxymethoxylated
General procedure for the synthesis of 3-alkyl-7-
epoxymethoxy-4-methylcoumarins (6 and 7).
The titled
coumarins 6 and 7 (43.1 mmol), sodium azide (215.5 mmol),
and ammonium chloride (103.5 mmol) were added to a solution
of methanol–water (50 mL, 4:1 v/v). The reaction mixture was
coumarins were synthesized in two steps. In the first step,
concentrated sulfuric acid (5 mL) was added dropwise into a
mixture of resorcinol (1, 9.0 mmol) and alkylated ethyl
ꢀ
carried at 70 C, and the conversion of the starting compound
ꢀ
acetoacetate (2/3, 15.4 mmol) under stirring at 0 C. The mixture
into the product was monitored by TLC. Upon completion of
the reaction, methanol was evaporated followed by the addition
of water (50 mL) to the residue. The product was extracted with
was stirred at room temperature for 3 to 4 h. On completion of
the reaction after 6 h as indicated by TLC examination, 100 mL
ice/water was added to precipitate the compound. The crude
solid thus obtained was filtered, washed with water, dried, and
crystallized from ethanol to give the 3-ethyl-7-hydroxy-4-
methylcoumarin 4 and 3-hexyl-7-hydroxy-4-methylcoumarin 5 in
CHCl
over Na
3
(3 Â 30 mL), and the organic layer was combined, dried
2
SO , and solvent removed under reduced pressure to
4
afford the crude product. The crude product thus obtained was
purified by column chromatography on silica gel using
EtOAc : petroleum ether (1:9) as an eluent to obtain pure
epoxymethoxylated coumarins 6 and 7. The alcohols 8 and 9
were purified by column chromatography using EtOAc : petroleum
ether (1:9) as an eluting solvent to obtain pure 7-(3-azido-2-
hydroxypropyloxy)-3-alkyl-4-methylcoumarins 8 and 9 in 90 and
85% yield, respectively.
7
8 and 80% yields, respectively, as pale yellow colored crystals.
In the second step, 3-alkyl-7-hydroxy-4-methylcoumarin (4/5,
5
.7 mmol) was added into 0.6 M NaOH solution (50 mL) in
ꢀ
methanol (30mL) with constant stirring at 0 C followed by
dropwise addition of epichlorohydrin (8.52 mmol), and the stirring
of the reaction was continued for 24h at room temperature. After
completion of the reaction as indicated by TLC examination,
methanol was completely evaporated under reduced pressure, and
the residue thus obtained was extracted with chloroform
7-(3-Azido-2-hydroxypropyloxy)-3-ethyl-4-methylcoumarin (8).
ꢀ
It was obtained as white solid, mp 88–90 C; IR (KBr): 2858, 2113,
À1
1
1714, 1617, 1392, 1288, 1156, 1078, and 746 cm
(400MHz, CDCl ): d 1.14 (3H, t, J =8.1Hz, ─CH
(3H, s, C-4 CH ), 2.66 ( 2H, q, J =7.3Hz, ─CH CH
dd, J= 5.1 and 2.9 Hz, ─CH N), 2.94 (1H, t, J=5.1Hz, ─CH
3.39 (1H, m, ─CH), 3.96 (1H, dd, J= 11 and 5.9 Hz, ─OCH ), 4.33
(1H, dd, J = 11 and 2.9 Hz, ─OCH ), 6.80 (1H, d, J = 2.2 Hz,
C-8H), 6.89 (1H, dd, J = 9.5 and 2.9 Hz, C-6H), 7.51 (1H, d,
;
H-NMR
CH ), 2.39
), 2.79 (1H,
N),
(
4Â 50mL) and washed with brine (2Â 20mL). Organic layer
3
2
3
was separated and dried over anhydrous Na SO . The solvent was
2
4
3
2
3
removed under reduced pressure, and the crude product thus
obtained was purified by column chromatography on silica gel
using EtOAc : petroleum ether (2:8) as an eluent to obtain pure
epoxymethoxylated coumarins 6 and 7 in 72 and 70% yield,
respectively.
a
b
a
b
1
3
J = 8.8 Hz, C-5H); C-NMR (100.6 MH
, CDCl ): d 13.04
Z
3
7
-Epoxymethoxy-3-ethyl-4-methylcoumarins (6).
It was
(─CH CH ), 14.48 (C-4 CH ), 20.74 (─CH CH ), 44.49
(─CH N), 49.77 (─CH), 69.02 (─OCH ), 101.21 (C-8),
2 2
2
3
3
2
3
ꢀ
obtained as white solid, mp 103–105 C; IR (KBr): 2859, 1720,
À1
1
1
607, 1389, 1281, 1151, 1069, and 841 cm
400 MHz, CDCl ): d 1.14 (3H, t, J = 7.3 Hz, ─CH
3H, s, C-4 CH ), 2.66 (2H, q, J = 7.3 Hz, ─CH CH ), 3.52–3.61
;
H-NMR
112.23 (C-6), 114.63 (C-10), 125.11 (C-3), 125.43 (C-5), 145.67
(C-9), 153.42 (C-4), 160.21 (C-7), 161.81 (CO); HR-ESI-TOF-
(
(
(
3
2
CH ), 2.39
3
+
+
MS m/z 326.1099 ([M + Na] ), calcd for [C H N O + Na]
3
2
3
15 17 3 4
2H, m, ─CH of epoxide), 4.07–4.27 (3H, m, ─CH of epoxide
326.1111.
2
and ─OCH
J= 8.8 and 2.2 Hz, C-6H), 7.50 (d, 1H, J= 8.8 Hz, C-5H); C-NMR
100.6 MH , CDCl ): d 13.03 (─CH CH ), 14.49 (C-4
2
), 6.80 ( 1H, d, J = 2.2 Hz, C-8H), 6.86 (1H, dd,
7-(3-Azido-2-hydroxypropyloxy)-3-hexyl-4-methylcoumarins (9).
13
ꢀ
It was obtained as white solid, mp 84–86 C; IR (KBr): 2860, 2111,
À1
1
(
1710, 1614, 1389, 1279, 1183, 1092, and 747 cm
(400 MHz, CDCl ): d 0.89 (3H, t, J=7.3Hz, ─(CH
1.28–1.41 (6H, m, ─CH CH (CH CH ), 1.48–1.55 (2H, m,
─CH CH (CH CH ), 2.38 (3H, s, C-4 CH ), 2.62 (2H,
t, J = 7.3 Hz, ─CH (CH CH ), 2.79 (1H, dd, J = 4.4 and 2.2 Hz,
─CH N), 2.94 (1H, t, J = 5.1 Hz, ─CH N), 3.39 (1H, m, ─CH),
3.96 (1H, dd, J = 11 and 5.9 Hz, ─OCH ), 4.33 (1H, dd, J = 10.9
and 2.9 Hz, ─OCH ), 6.80 (1H, d, J = 2.2 Hz, C-8H), 6.89 (1H,
;
H-NMR
Z
3
2
3
CH ), 20.74 (─CH CH ), 53.27 (─CH of epoxide), 68.96
3
2
)
5
CH ),
3
3
2
3
2
(
(
(
─OCH ), 69.36 (─CH of epoxide), 101.29 (C-8), 112.06
C-6), 114.74 (C-10), 125.16 (C-3), 125.47 (C-5), 145.82
C-9), 153.36 (C-4), 160.07 (C-7), 161.94 (CO); HR-ESI-
TOF-MS m/z 261.1115 ([M + H] ), calcd for [C H O + H]
61.1121.
2
2
)
2 3
3
2
)
2
2
2
3
3
3
)
2
2
4
3
+
+
1
5 16 4
a
b
2
a
7
-Epoxymethoxy-3-hexyl-4-methylcoumarins (7).
It was
b
ꢀ
obtained as white solid, mp 104–105 C; IR (KBr): 2851, 1718,
dd, J = 9.5 and 2.9Hz, C-6H), 7.51 (1H, d, J = 8.8 Hz, C-5H);
À1
1
13
1
(
1
─
610, 1389, 1277, 1121, 1060, and 844 cm
400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH
.30–1.40 (6H, m, ─CH CH (CH CH ), 1.47–1.53 (2H, m,
CH CH (CH CH ), 2.38 (3H, s, C-4 CH ), 2.63 (2H, t,
J = 7.3 Hz, ─CH (CH ) CH ), 3.52–3.60 (2H, m, ─CH of
epoxide), 4.06–4.23 (3H, m, ─CH of epoxide and ─OCH2),
.79 ( 1H, d, J = 2.2 Hz, C-8H), 6.86 (1H, dd, J = 8.8 and
.2 Hz, C-6H), 7.51 (d, 1H, J = 8.8 Hz, C-5H); C-NMR
;
H-NMR
C-NMR (100.6 MH , CDCl ): d 14.04 (─(CH ) CH ), 14.79
Z
3
2 5
3
3
2
)
5
CH ),
3
(C-4CH
(CH
CH
3
), 22.58 (─CH
2
(CH
CH
2
N), 49.78 (─CH), 69.03 (─OCH ),
2
)
3
CH
2
CH
3
), 27.49 (─CH
2 2
CH
2
2
2
)
3
3
2
)
3
CH
3
), 28.74 (─(CH
), 44.51 (─CH
2
)
2
2
(CH
)
2 2
CH ), 29.33 (─(CH )
3
2
2
2
2
)
3
3
3
3
2
CH CH
2
3
2
101.21 (C-8), 112.24 (C-6), 114.67 (C-10), 124.03 (C-3), 125.44
(C-5), 145.84 (C-4), 153.44 (C-9), 160.19 (C-7), 161.95 (CO);
2
2 4
3
2
+
6
2
HR-ESI-TOF-MS m/z 360.1900 ([M + Na] ), calcd for
13
+
[C19H N O
25 3 4
+ Na] 360.1918.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
+
+
General procedure for the synthesis of propargyl ethers
MS m/z 402.1656 ([M + H] ), calcd for [C H N O +H]
20 23 3 6
1
4a–u.
To a stirred solution of substituted phenols (13a–u,
402.1660.
3-Ethyl-7-[2-hydrox-3-(4-g-chloropropyl-1,2,3-triazol-1-yl)
propyloxy]-4-methylcoumarin (11c). It was obtained as
5
0.0 mmol) in acetone (80 mL), equimolar amount of propargyl
bromide and K
2
CO
3
(150.0 mmol) were added. The reaction
ꢀ
ꢀ
mixture was refluxed at 60 C for 12 h. On completion of the
reaction as indicated by the TLC, the solvent was removed
under reduced pressure followed by addition of water (30 mL)
to the residue. The compound was extracted with chloroform
white solid in 88% yield; mp 104–108 C; IR (KBr): 3398,
2922, 2854, 1713, 1609, 1387, 1281, 1181, 1093, and
À1
1
822 cm
t, J=7.3Hz, ─CH
2.39 (3H, s, C-4 CH
(2H, t, J =7.7Hz, ─CH CH CH Cl), 3.67 (2H, t, J=6.9Hz,
;
H-NMR (400 MHz, DMSO-d ): d 1.05 (3H,
6
2 3 2 2 2
CH ), 2.04 (2H, pentate, ─CH CH CH Cl),
(
3 Â 30 mL), the combined organic solvent was dried over
3 2 3
), 2.56 (2H, q, J=7.3Hz, ─CH CH ), 2.75
anhydrous Na SO , and the solvent was evaporated under
2
4
2
2
2
reduced pressure to afford propargyl ethers 14a–u, which were
used as such for the next reaction.
General procedure for the synthesis of 7-[2-hydroxy-3-(1,2,3-
triazol-1-yl)propyloxy]-3-ethyl-/hexyl-4-methylcoumarins 11a–d,
─CH CH CH Cl), 4.01–4.07 (2H, m, ─CH N), 4.21–4.26
2 2 2 2
(1H, m, ─CH), 4.41 (1H, dd, J = 13.9 and 7.4 Hz, ─OCH
(1H, dd, J= 13.9 and 3.6 Hz, ─OCH ), 5.62 (1H, d, J=5.1Hz,
OH), 6.95–6.98 (2H, m, C-6H and C-8H), 7.70 (1H, d, J=8.7Hz,
a
), 4.56
b
13
1
2a–d, 15a–u, and 16a–u.
hydroxypropyloxy)-3-ethyl-/hexyl-4-methylcoumarin (8/9, 3.60mmol)
and alkynes (10a–d or 14a–u, 4.3 mmol) in t-BuOH/H O/THF
3 mL, 1/1/1, v/v/v) were added sodium ascorbate (1.3 mmol)
To a solution of 7-(3-azido-2-
C-5H), 7.89 (1H, s, triazole H); C-NMR (100.6 MH
): d 12.96 (─CH CH ), 14.32 (C-4 CH ), 20.20 (─CH
22.28 (─CH CH CH Cl), 31.79 (─CH CH CH Cl), 44.68
(─CH CH CH Cl), 52.34 (─CH N), 67.68 (─CH), 70.07
(─OCH ), 101.00 (C-8), 112.29 (C-6), 113.85 (C-10), 123.14
Z
, DMSO-
d
6
CH ),
2
2
3
3
3
2
2
2
2
2
2
2
(
2
2
2
2
and copper(II) sulfate pentahydrate (0.5 mmol). Thereafter, the
2
ꢀ
reaction mixture was stirred at 60 C, and the reaction was
(C-3), 123.80 (CH═C), 126.31 (C-5), 145.17 (CH═C), 146.39
monitored by TLC. On completion of the reaction as indicated
by TLC examination, the solvent was evaporated under reduced
pressure, and the crude product thus obtained was purified by
silica gel column chromatography using methanol/chloroform as
eluent to afford the desired products 11a–d, 12a–d, 15a–u, and
(C-9), 153.03 (C-4), 160.42 (C-7), 160.74 (CO); HR-ESI-TOF-
+
+
MS m/z 406.1521 ([M + H] ), calcd for [C20
H
24ClN
3
O
4
+ H]
406.1528.
3-Ethyl-7-[2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)
propyloxy]-4-methylcoumarin (11d). It was obtained as
ꢀ
1
6a–u in moderate to good yields.
white solid in 92% yield; mp 101–103 C; IR (KBr): 3305,
3
-Ethyl-7-[2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy]-
2922, 2854, 1676, 1617, 1307, 1230, 1163, 1098, and
À1
1
4
-methylcoumarin (11a). It was obtained as white solid in 85%
828 cm
;
6
H-NMR (400 MHz, DMSO-d ): d 0.96 (3H, t,
ꢀ
yield; mp 140–143 C; IR (KBr): 3386, 2925, 2854, 1708, 1610,
J = 7.3 Hz, ─CH CH ), 2.31 (3H, s, C-4 CH ), 2.47 (2H, q,
2
3
3
À1
1
1387, 1253, 1172, 1093, and 766 cm
;
H-NMR (400 MHz,
J = 7.3 Hz, ─CH CH ), 3.92–3.99 (2H, m, ─CH N), 4.13–4.20
2 3 2
(1H, m, ─CH), 4.36 (1H, dd, J = 13.9 and 8.1 Hz, ─OCHa),
DMSO-d ): d 1.04 (3H, t, J =7.3Hz, ─CH CH ), 2.39 (3H, s, C-4
6
2
3
CH ), 2.57 (2H, q, J =7.3 Hz, ─CH CH ), 4.08–4.16 (2H, m,
4.43 (2H, d, J = 5.1 Hz, ─CH OH), 4.49 (1H, dd, J = 13.9 and
3
2
3
2
─
CH
2
N), 4.31–4.35 (1H, m, ─CH), 4.48 (1H, dd, J= 13.3 and
), 4.68 (1H, dd, J = 13.9 and 3.7 Hz, ─OCH ),
3.7 Hz, ─OCH ), 5.10 (1H, t, J = 5.5 Hz, ─CH OH), 5.54 (1H,
b
2
7
5
7
.3 Hz, ─OCH
a
b
d, J = 5.8 Hz, OH), 6.88–6.90 (2H, m, C-6H and C-8H), 7.63
1
3
.70 (1H, d, J =5.8Hz, OH), 6.97–7.00 (2H, m, C-6H and C-8H),
.31 (1H, t, J= 7.4 Hz, ArH), 7.42–7.47 (2H, m, ArH), 7.71 (1H,
(1H, d, J = 9.6 Hz, C-5H), 7.86 (1H, s, triazole H); C-NMR
(100.6 MHz, DMSO-d ): d 12.99 (─CH CH ), 14.36 (C-4 CH ),
6
2
3
3
d, J=9.5Hz, C-5H), 7.85–7.86 (2H, m, ArH), 8.57 (1H, s, triazole
2 3 2 2
20.24 (─CH CH ), 52.33 (─CH N), 55.08 (─CH═C─CH ),
1
3
H); C-NMR (100.6 MH
C-4 CH ), 20.21 (─CH
0.09 (─OCH ), 101.06 (C-8), 112.31 (C-6), 113.87 (C-10), 122.45
C-3), 123.81 (CH═C), 125.10 (2-ArC), 126.32 (C-5), 127.75,
28.88, 130.86 (4-ArC), 146.09 (CH═C), 146.39 (C-9), 153.04 (C-4),
60.43 (C-7), 160.75 (CO); HR-ESI-TOF-MS m/z 406.1751
Z
, DMSO-d
6
): d 12.97 (─CH
2
CH
3
), 14.32
67.75 (─CH), 70.09 (─OCH ), 101.04 (C-8),112.33 (C-6), 113.89
2
(
7
(
1
1
(
3
2
CH ), 52.71 (─CH
3
2
N), 67.69 (─CH),
(C-10), 123.73 (C-3), 123.84 (─CH═C), 126.36 (C-5), 146.45
2
(─CH═C), 147.75 (C-9), 153.05 (C-4), 160.45 (C-7), 160.79
+
(CO); HR-ESI-TOF-MS m/z 382.1365 ([M + Na] ), calcd for
+
[C H N O + Na] 382.1373.
1
8
21
3
5
3-Hexyl-7-[2-hydroxy-3-(4-phenyl-1,2,3-triazol-1-yl)propyloxy]-
+
+
[M + H] ), calcd for [C23
H N O
23 3 4
+H] 406.1761.
4-methylcoumarin (12a). It was obtained as white solid in 84%
ꢀ
3
-Ethyl-7-[2-hydroxy-3-(4-propylcarboxylicacid)-1,2,3-triazol-
yield; mp 136–139 C; IR (KBr): 3386, 2925, 2854, 1708, 1610,
À1
1
1
-yl)propyloxy]-4-methylcoumarin (11b).
It was obtained as
1387, 1253, 1172, 1093, and 766 cm
; H-NMR (400 MHz,
ꢀ
white solid in 80% yield; mp 123–126 C; IR (KBr): 3461, 2920,
DMSO-d ): d 0.86 (3H, t, J=7.3Hz, ─(CH ) CH ), 1.27–1.33
6
2 5
3
À1
1
2
859, 1704, 1617, 1303, 1211, 1159, 1089, and 865 cm ; H-
NMR (400 MHz, DMSO-d ): 1.05 (3H, t, J=7.3Hz,
CH CH ), 2.39 (3H, s, C-4 CH ), 2.53–2.60 (4H, m, ─CH CH
(6H, m, ─CH CH (CH ) CH ), 1.39–1.43 (2H, m, ─CH CH
2 2 2 3 3 2
2
6
d
(CH ) CH ), 2.38 (3H, s, C-4 CH ), 2.53 (2H, q, J=7.3Hz, ─CH
2 3 3 3
2
─
2 4 3 2
(CH ) CH ), 4.06–4.14 (2H, m, ─CH N), 4.31–4.35 (1H, m,
2
3
3
2
3
and ─CH CH COOH), 2.85 (2H, t, J=7.3Hz, ─CH CH COOH),
─CH), 4.50 (1H, dd, J= 13.9 and 8.4 Hz, ─OCH ), 4.68
2
2
2
2
a
4
.01–4.08 (2H, m, ─CH
dd, J= 13.9 and 7.3 Hz, ─OCH
.6 Hz, ─OCH ), 5.61 (1H, brs, OH), 6.95–6.97 (2H, m, C-6H
and C-8H), 7.70 (1H, d, J =8.7Hz, C-5H), 7.85 (1H, s, triazole H),
2
N), 4.20–4.26 (1H, m, ─CH), 4.39 (1H,
(1H, dd, J= 13.9 and 3.6 Hz, ─OCH ), 5.70 (1H, d, J=5.1Hz,
b
a
), 4.55 (1H, dd, J=13.9 and
OH), 6.96–6.99 (2H, m, C-6H and C-8H), 7.33 (1H, t, J = 7.4 Hz,
3
b
ArH), 7.45 (2H, t, J = 7.7 Hz, ArH), 7.70 (1H, d, J = 9.6 Hz,
C-5H), 7.86 (2H, d, J = 7.3 Hz, ArH), 8.57 (1H, s, triazole H);
13
13
1
d
2
2.17 (1H, s, ─CH CH COOH); C-NMR (100.6 MH , DMSO-
C-NMR (100.6 MH , DMSO-d ): d 13.96 (─(CH ) CH ),
2
2
Z
Z
6
2 5
3
6
): d 12.89 (─CH
0.60 (─CH CH COOH), 33.09 (─CH
N), 67.65 (─CH), 70.00 (─OCH
2 3 3 2 3
CH ), 14.25 (C-4 CH ), 20.15 (─CH CH ),
2 2 3 2 3
14.63 (C-4 CH3), 22.70 (─CH (CH ) CH CH ), 27.40
2
2
2 2
CH COOH), 52.28
(─CH CH (CH ) CH ), 29.4 (─(CH ) CH (CH ) CH ), 31.90
2 2 2 3 3 2 2 2 2 2 3
(
─CH
2
2
), 100.95 (C-8),
(─(CH ) CH CH CH ), 52.70 (─CH N), 67.69 (─CH), 70.09
2 3 2 2 3 2
1
1
1
12.23 (C-6), 113.79 (C-10), 122.92 (C-3), 123.75 (CH═C),
26.24 (C-5), 145.36 (CH═C), 146.33 (C-9), 152.96 (C-4),
60.35 (C-7), 160.69 (CO), 173.58 (COOH); HR-ESI-TOF-
(─OCH ), 101.05 (C-8), 112.30 (C-6), 113.86 (C-10), 122.45 (C-3),
123.81 (CH═C), 125.10 (2-ArC), 126.32 (C-5), 127.75,128.87,
130.86 (4-ArC), 146.08 (CH═C), 156.39 (C-9), 153.04 (C-4),
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
1
60.42 (C-7), 160.75 (CO); HR-ESI-TOF-MS m/z 462.2381
DMSO-d ): d 12.99 (─(CH ) CH ), 14.36 (C-4 CH ), 22.50 (─CH
6 2 5 3 3 2
+
+
(
[M + H] ), calcd for [C H N O + H] 462.2387.
(CH ) CH CH ), 27.40 (─CH CH (CH ) CH ), 31.90 (─(CH )
2
7
31
3
4
2 3
2
3
2
2
2 3
3
2
3
-Hexyl-7-[2-hydroxy-3-(4-propylcarboxylicacid-1,2,3-triazol-
3
CH
2
CH
2
CH
3
), 52.33 (─CH
2
N), 55.07 (─CH═C─CH
2
), 67.75
1
-yl)propyloxy]-4-methylcoumarin (12b).
It was obtained as
(─CH), 70.09 (─OCH ), 101.04 (C-8), 112.33 (C-6), 113.88 (C-
2
ꢀ
white solid in 82% yield; mp 118–120 C; IR (KBr): 3461, 2920,
2
NMR (400 MHz, DMSO-d ): d 0.86 (3H, t, J = 7.3 Hz, ─(CH )
10), 123.72 (C-3), 123.84 (─CH═C), 126.36 (C-5), 145.75
(─CH═C), 147.29 (C-9), 153.05 (C-4), 160.45 (C-7), 160.79
À1
1
859, 1704, 1617, 1303, 1211, 1159, 1084, and 865 cm ; H-
+
(CO); HR-ESI-TOF-MS m/z 416.2176 ([M + H] ), calcd for
6
2
+
5
CH
3 2 2
), 1.24–1.35 (6H, m, ─CH CH (CH
2 3 3
) CH ), 1.39–1.43
[C22
H
29
N
3
O
5
+H] 416.2180.
(
2 2 2 3 3 3
2H, m, ─CH CH (CH ) CH ), 2.38 (3H, s, C-4 CH ), 2.53–2.67
3-Ethyl-7-[2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)
(
4H, m, ─CH (CH ) CH and ─CH CH COOH), 2.85 (2H, t,
propyloxy]-4-methylcoumarin (15a). It was obtained as white
2
2 4
3
2
2
ꢀ
J = 7.3 Hz, ─CH CH COOH), 3.99–4.07 (2H, m, ─CH N),
4
solid in 85% yield; mp 128–130 C; IR (KBr): 3386, 2925, 2854,
2
2
2
À1
1
.20–4.23 (1H, m, ─CH), 4.40 (1H, dd, J = 13.9 and 7.3 Hz,
OCH ), 4.55 (1H, dd, J = 13.9 and 3.8 Hz, ─OCH ), 5.61 (1H,
1717, 1610, 1387, 1253, 1172, 1093, and 766 cm ; H-NMR
(400 MHz, CDCl ): d 1.10 (3H, t, J = 7.1 Hz, ─CH CH ), 2.34
(3H, s, C-4 CH ), 2.62 (2H, q, J = 7.3 Hz, ─CH CH ), 3.45
─
a
b
3
2
3
d, J = 5.1 Hz, OH), 6.95–6.98 (2H, m, C-6H and C-8H), 7.69 (1H,
d, J = 9.5 Hz, C-5H), 7.84 (1H, s, triazole H), 12.17 (1H, d,
3
2
3
(1H, brs, OH), 4.01–4.05 (2H, m, ─CH N), 4.47–4.56 (2H, m,
2
1
3
─
CH CH COOH); C-NMR (100.6MH , DMSO-d ): d 13.96
─CH and ─OCH ), 4.69 (1H, dd, J= 13.9 and 3.8 Hz, ─OCH ),
2
2
Z
6
a
b
(
(
(
─(CH
─CH
─(CH
2
)
5
CH
3
, C-4 CH
3
), 14.63 (─CH
2
(CH
2
)
3
CH
)CH
CH CH
2
CH
3
), 20.69
28.20
), 33.17
5.14 (2H, s, ─CH
2
OPh), 6.72–6.73 (1H, m, C-8H), 6.80
2
CH
2
COOH), 22.07 (─CH
2
CH
2
(CH
CH
2
3
),
(1H, dd, J = 8.7 and 2.3 Hz, C-6H), 6.90–6.94 (3H, m, ArH), 7.24
(2H, t, J = 7.3 Hz, ArH), 7.44 (1H, d, J = 8.8 Hz, C-5H), 7.78 (1H,
)
2 2
CH
2
(CH CH ), 31.12 (─(CH
)
2 2
3
)
2 3
2
2
3
13
(─CH CH COOH), 52.36 (─CH N), 67.73 (─CH), 70.09
s, triazole H);
C-NMR (100.6 MHz, CDCl3): d 13.03
2
2
2
(
─OCH ), 101.04 (C-8), 112.32 (C-6), 113.87 (C-10), 122.61 (C-3),
(─CH CH ), 14.48 (C-4 CH ), 20.72 (─CH CH ), 52.99
2
2
3
3
2
3
123.00 (CH═C), 126.34 (C-5), 145.45 (CH═C), 146.67 (C-9),
2 2 2
(─CH N), 61.59 (─OCH Ph), 68.29 (─CH), 69.25 (─OCH ),
1
53.05 (C-4), 160.44 (C-7), 160.93 (CO), 173.66 (COOH); HR-ESI-
101.28 (C-8), 112.15 (C-6), 114.60 (C-10), 114.71 (2-ArC),
121.21 (C-3), 124.59 (CH═C), 125.05 (ArC), 125.48
(C-5), 129.46 (2-ArC), 143.88 (CH═C), 145.91 (C-9), 153.26 (C-
4), 158.02 (C-7), 159.93 (ArC), 161.95 (CO); HR-ESI-TOF-MS
+
+
TOF-MS m/z 458.2284 ([M + H] ), calcd for [C24
58.2286.
-Hexyl-7-[2-hydrox-3-(4-g-chloropropyl-1,2,3-triazol-1-yl)
propyloxy]-4-methylcoumarin (12c). It was obtained as
white solid in 86% yield; mp 99–102 C; IR (KBr): 3398,
31 3 6
H N O +H]
4
3
+
+
25 3 5
m/z 436.1858 ([M + H] ), calcd for [C24H N O + H] 436.1867.
ꢀ
3-Ethyl-7-[2-hydroxy-3-(4-o-chlorophenoxymethyl-1,2,3-
2
7
922, 2854, 1713, 1609, 1387, 1252, 1181, 1093, and
triazol-1-yl)propyloxy]-4-methylcoumarin (15b).
obtained as white solid in 92% yield; mp 136–139 C; IR
It was
À1
1
ꢀ
79 cm
;
H-NMR (400 MHz, DMSO-d ): d 0.84 (3H, t,
6
J = 6.6 Hz, ─(CH
CH ), 1.37–1.44 (2H, m, ─CH
pentate, ─CH CH CH Cl), 2.36 (3H, s, C-4 CH
2H, m, ─CH (CH ) CH ), 2.73 (2H, t, J = 7.4 Hz,
2
)
5
CH
3
), 1.23–1.34 (6H, m, ─CH
CH (CH CH ), 2.02 (2H,
), 2.48–2.52
2
CH
2
(CH
2
)
(KBr): 3392, 2926, 2367, 1718, 1617, 1458, 1251, 1170,
À1
1
3
3
2
2
2
)
3
3
1087, and 759 cm
(3H, t, J = 7.7 Hz, ─CH
(2H, q, J = 7.3 Hz, ─CH CH ), 3.81 (1H, brs, OH), 4.03–4.09
;
H-NMR (400 MHz, CDCl
3
): d 1.13
2
2
2
3
2
CH ), 2.37 (3H, s, C-4 CH
3
3
), 2.65
(
2
2 4
3
2
3
─
CH CH CH Cl), 3.65 (2H, t, J = 6.9 Hz, ─CH CH CH Cl),
(2H, m, ─CH N), 4.53–4.61 (2H, m, ─CH and ─OCH ), 4.74
2
2
2
2
2
2
2
a
3
(
.96–4.05 (2H, m, ─CH
1H, dd, J = 13.9 and 7.6 Hz, ─OCH
and 4.4 Hz, ─OCH ), 5.61 (1H, d, J = 5.8 Hz, OH), 6.92–6.95
2H, m, C-6H and C-8H), 7.67 (1H, d, J = 8.8 Hz, C-5H), 7.87
2
N), 4.20–4.24 (1H, m, ─CH), 4.38
(1H, dd, J = 13.2 and 2.2 Hz, ─OCH
6.76 (1H, d, J = 2.9 Hz, C-8H), 6.83 (1H, dd, J = 5.8 and 2.9 Hz,
C-6H), 6.87–6.91 (1H, m, ArH), 7.05–7.07 (1H, m, ArH),
b
2
), 5.25 (2H, s, ─CH OPh),
a
), 4.55 (1H, dd, J = 13.9
b
(
(
(
7.17–7.21 (1H, m, ArH), 7.31–7.33 (1H, m, ArH), 7.48 (1H,
1
3
13
1H, s, triazole H); C-NMR (100.6 MH , DMSO-d ): d 13.96
d, J=9.5Hz, C-5H), 7.86 (1H, s, triazole H);
(100.6 MHz, CDCl ): d 13.03 (─CH CH
(─CH CH ), 53.02 (─CH N), 62.97 (─OCH
2
69.24 (─OCH ), 101.24 (C-8), 112.16 (C-6), 114.06 (C-3), 114.71
C-NMR
Z
6
─(CH
2.29 (─(CH
─CH CH (CH
2
)
5
CH
3
), 14.63 (C-4 CH
3
), 22.08 (─CH
2
CH
CH
(CH CH
2
(CH
2
)
3
CH
3
),
3
2
3 3
), 14.48 (C-4CH ), 20.73
2
2 4
)
CH
CH
2
3
CH ), 26.82 (─CH
2
CH
2
2
Cl), 28.20
), 31.13
2
3
2
2
Ph), 68.30 (─CH),
(
(
(
(
(
2
2
)
2 3
3
), 28.67 (─(CH
) CH
2 2 2
2
)
2
3
─(CH ) CH CH CH ), 31.82 (─CH CH CH Cl), 44.69
─CH CH CH Cl), 52.36 (─CH N), 67.71 (─CH), 70.08
─OCH ), 101.01 (C-8), 112.29 (C-6), 113.86 (C-10), 122.60
2
C-3), 123.16 (CH═C), 126.33 (C-5), 145.20 (CH═C), 146.65
C-9), 153.04 (C-4), 160.42 (C-7), 160.92 (CO); HR-ESI-TOF-MS
(C-10), 122.02 (2-ArC), 122.91 (CH═C), 124.69 (ArC), 125.06 (C-
5), 127.74, 130.24 (2-ArC), 143.62 (CH═C), 145.91 (C-9), 153.27
(C-4), 153.54 (C-7), 159.92 (ArC), 161.95 (CO); HR-ESI-TOF-MS
2
3
2
2
3
2
2
2
2
2
2
2
+
+
3 5
m/z 470.1477 ([M + H] ), calcd for [C24H24ClN O +H] 470.1477.
(
3-Ethyl-7-[2-hydroxy-3-(4-m-chlorophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15c). It was obtained
as white solid in 85% yield; mp 111–113 C; IR (KBr): 3392,
+
+
m/z 462.2157 ([M + H] ), calcd for [C H ClN O +H] 462.2154.
24
32
3 4
ꢀ
3
-Hexyl-7-[2-hydroxy-3-(4-hydroxymethyl-1,2,3-triazol-1-yl)
propyloxy]-4-methylcoumarin (12d). It was obtained as white
2954, 2853, 1718, 1611, 1493, 1387, 1285, 1169, 1091, and
ꢀ
À1
1
solid in 92% yield; mp 106–108 C; IR (KBr): 3305, 2922, 2854,
3
825 cm ; H-NMR (400 MHz, CDCl ): d 1.08 (3H, t, J = 7.3 Hz,
À1
1
1
676, 1617, 1307, 1230, 1163, 1013, and 828 cm ; H-NMR
─CH CH ), 2.35 (3H, s, C-4 CH ), 2.62 (2H, q, J=7.4Hz,
2
3
3
(
400 MHz, DMSO-d ): d 0.86 (3H, t, J = 6.6 Hz, ─(CH ) CH ),
─CH CH ), 3.76 (1H, brs, OH), 4.01–4.06 (2H, m, ─CH N),
6
2 5
3
2
3
2
1
─
.23–1.36 (6H, m, ─CH
2
CH
2
(CH
2
)
3
CH
3
), 1.37–1.46 (2H, m,
), 2.50–2.55
), 4.00–4.05 (2H, m, ─CH N), 4.23–
4.50–4.60 (2H, m, ─CH and ─OCH
3.8 Hz, ─OCH ), 5.13 (2H, s, ─CH
6H, C-8H, and 3 Â ArH), 7.15 (1H, t, J= 8.1 Hz, ArH), 7.45 (1H,
a
), 4.71 (1H, dd, J= 13.9 and
2
OPh), 6.74–6.93 (5H, m, C-
CH
2
CH
2
(CH
2
)
3
CH
3
), 2.39 (3H, s, C-4 CH
CH
3
b
(
2H, m, ─CH
2
(CH
2
)
4
3
2
13
4
4
3
.26 (1H, m, ─CH), 4.44 (1H, dd, J = 13.9 and 7.3 Hz, ─OCHa),
.52 (2H, d, J=5.8Hz, ─CH OH), 4.58 (1H, dd, J=13.9 and
.8 Hz, ─OCH
d, J=8.8Hz, C-5H), 7.79 (1H, s, triazole H);
C-NMR
(100.6 MHz, CDCl ): d 13.03 (─CH CH ), 14.50 (C-4 CH ),
2
3
2
3
3
b
), 5.18 (1H, t, J=5.9Hz, ─CH
2
OH), 5.62 (1H, d,
20.74 (─CH
(─CH), 69.26 (─OCH
(C-3), 114.77 (C-10), 115.22 (2-ArC), 121.41 (CH═C), 124.69
2 3 2 2
CH ), 53.00 (─CH N), 61.87 (─OCH Ph), 68.32
J=5.9Hz, OH), 6.96–6.98 (2H, m, C-6H and C-8H), 7.70 (1H, d,
J= 9.5Hz, C-5H), 7.95 (1H, s, triazole H); C-NMR (100.6 MHz,
2
), 101.29 (C-8), 112.13 (C-6), 112.96
13
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
(
1
1
ArC), 125.12 (C-5), 125.51, 130.25 (2-ArC), 143.34 (CH═C),
3-Ethyl-7-[2-hydroxy-3-(4-o-nitrophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15 g). It was
obtained as white solid in 85% yield; mp 136–139 C; IR (KBr):
45.89 (C-9), 153.28 (C-4), 158.74 (C-7), 159.90 (ArC),
+
ꢀ
61.94 (CO); HR-ESI-TOF-MS m/z 470.1480 ([M + H] ),
+
calcd for [C24
H
24ClN
3
O
5
+ H] 470.1477.
3419, 2924, 2856, 1689, 1612, 1523, 1466, 1347, 1255, 1163,
À1
1
3
-Ethyl-7-[2-hydroxy-3-(4-p-chlorophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15d). It was
obtained as white solid in 81% yield; mp 127–129 C; IR (KBr):
392, 2927, 2859, 1718, 1607, 1389, 1281, 1151, 1069, and
1090, and 739 cm
6
; H-NMR (400MHz, DMSO-d ): d 1.05
(3H, t, J = 7.3 Hz, ─CH CH ), 2.39 (3H, s, C-4 CH ), 2.57 (2H,
2
3
3
ꢀ
q, J = 7.2 Hz, ─CH CH ), 4.01–4.10 (2H, m, ─CH N), 4.22–4.28
2
3
2
3
8
(1H, m, ─CH), 4.48 (1H, dd, J = 13.9 and 7.3 Hz, ─OCH ), 4.62
2
(1H, dd, J = 13.9 and 3.8 Hz, ─OCH ), 5.36 (2H, s, ─CH OPh),
a
À1
1
41 cm ; H-NMR (400 MHz, CDCl
3
): d 1.13 (3H, t, J=7.7Hz,
b
─
─
CH CH ), 2.36 (3H, s, C-4 CH ), 2.64 (2H, q, J=7.3Hz,
5.64 (1H, d, J = 5.1Hz, OH), 6.94–6.97 (2H, m, C-6H and
C-8H), 7.11–7.15 (1H, m, ArH), 7.59–7.72 (3H, m, ArH), 7.85
2
3
3
CH CH ), 3.94 (1H, brs, OH), 4.03–4.11 (2H, m, ─CH N), 4.51–
2
3
2
13
4
2
.60 (2H, m, ─CH and ─OCH
.2 Hz, ─OCH ), 5.14 (2H, s, ─CH
a
), 4.74 (1H, dd, J= 13.9 and
(1H, d, J = 8.4 Hz, C-5H), 8.22 (1H, s, triazole H); C-NMR
(100.6 MHz, DMSO-d ): d 12.89 (─CH CH ), 14.25 (C-4 CH ),
20.14 (─CH CH ), 52.49 (─CH N), 62.48 (─OCH Ph), 67.53
b
2
OPh), 6.74 (1H, d, J=2.9Hz,
6
2
3
3
C-8H), 6.81 (1H, dd, J= 9.5 and 2.9 Hz, C-6H), 6.85–6.88 (2H,
m, ArH), 7.17–7.21 (2H, m, ArH), 7.46 (1H, d, J=8.8Hz, C-
2
3
2
2
(─CH), 69.98 (─OCH ), 100.93 (C-8), 112.24 (C-6), 113.80
2
13
5H), 7.82 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl ): d
(C-10), 115.50 (2-ArC), 120.81 (CH═C), 123.75 (C-3), 124.85
(ArC), 125.84 (C-5), 126.25, 134.21 (2-ArC), 139.66 (CH═C),
146.34 (C-9), 150.54 (C-4), 152.96 (C-7), 160.32 (ArC),
3
13.02 (─CH
2 3 3 2 3
CH ), 14.49 (C-4 CH ), 20.73 (─CH CH ), 53.00
(─CH
2
N), 61.89 (─OCH
2
Ph), 68.28 (─CH), 69.27 (─OCH
2
),
+
1
1
1
1
4
01.23 (C-8), 112.16 (C-6), 114.71 (C-10), 115.94 (2-ArC),
24.70 (C-3), 125.06 (CH═C), 125.49 (ArC), 126.07 (C-5),
29.28 (2-ArC), 143.45 (CH═C), 145.95 (C-9), 153.23 (C-4),
56.59 (C-7), 159.89 (ArC), 161.95 (CO); HR-ESI-TOF-MS m/z
70.1474 ([M + H] ), calcd for [C24
-Ethyl-7-[2-hydroxy-3-(4-o-bromophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15e). It was
obtained as white solid in 91% yield; mp 132–136 C; IR (KBr):
160.69 (CO); HR-ESI-TOF-MS m/z 481.1711 ([M + H] ), calcd
+
for [C H N O + H] 481.1718.
2
4 24 4 7
3-Ethyl-7-[2-hydroxy-3-(4-m-nitrophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15h). It was
+
+
ꢀ
H24ClN O
3 5
+H] 470.1477.
obtained as white solid in 88% yield; mp 136–140 C; IR (KBr):
3
3210, 2929, 2869, 1716, 1618, 1527, 1350, 1251, 1163, 1062,
À1
1
and 829 cm
; H-NMR (400 MHz, CDCl ): d 1.14 (3H, t,
3
ꢀ
J = 7.3Hz, ─CH CH ), 2.38 (3H, s, C-4 CH ), 2.66 (2H,
2
3
3
3
246, 2931, 2859, 1710, 1618, 1479, 1384, 1297, 1156, 1069,
q, J = 7.3 Hz, ─CH
(2H, m, ─CH N), 4.50–4.62 (2H, m, ─CH and ─OCH ), 4.75
2 a
(1H, dd, J = 13.8 and 3.2 Hz, ─OCH ), 5.28 (2H, s, ─CH OPh),
2
CH
3
), 3.35 (1H, brs, OH), 4.00–4.10
À1
1
and 759cm
;
3
H-NMR (400 MHz, CDCl ): d 1.14 (3H, t,
J = 7.3 Hz, ─CH CH ), 2.37 (3H, s, C-4 CH3), 2.65
2
3
b
2
(
(
(
2H, q, J = 8.1 Hz, ─CH CH ), 3.72 (1H, brs, OH), 4.03–4.09
6.76 (1H, d, J = 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.7 and 2.8 Hz,
C-6H), 7.30–7.51 (3H, m, ArH), 7.81–7.86 (3H, m, ArH, C-5H
2
3
2H, m, ─CH
1H, dd, J = 13.2 and 2.9 Hz, ─OCH
.77 (1H, d, J = 2.9Hz, C-8H), 6.81–6.86 (2H, m, C-6H and
2
N), 4.51–4.61 (2H, m, ─CH and ─OCH
a
), 4.73
13
b
), 5.26 (2H, s, ─CH
2
OPh),
and triazole H);
(─CH CH ), 14.52 (C-4 CH
(─CH N), 63.39 (─OCH Ph), 68.39 (─CH), 69.19 (─OCH ),
3
C-NMR (100.6 MHz, CDCl ): d 13.05
6
2
3
3
), 20.77 (─CH CH
2
3
), 52.99
ArH), 7.03 (1H, dd, J = 8.1 and 1.8 Hz, ArH), 7.21–7.27 (1H, m,
ArH), 7.47–7.51 (2H, m, ArH and C-5H), 7.86 (1H, s, triazole
2
2
2
101.36 (C-8), 112.13 (C-6), 112.74 (C-10), 114.81 (2-ArC),
123.18 (CH═C and C-3), 124.63 (ArC), 125.54 (C-5), 129.55 (2-
ArC), 139.38 (CH═C), 145.83 (C-9), 153.33 (C-4), 156.59 (C-7),
159.92 (ArC), 161.92 (CO); HR-ESI-TOF-MS m/z 481.1710
13
H);
4.55 (C-4CH
─OCH Ph), 68.48 (─CH), 69.13 (─OCH
C-6), 113.92 (C-3), 114.91 (C-10), 122.57 (2-ArC), 124.55
CH═C), 125.30 (ArC), 125.57 (C-5), 128.55, 133.36 (2-ArC),
43.85 (CH═C), 145.76 (C-9), 153.38 (C-4), 154.43 (C-7), 159.85
C-NMR (100.6MHz, CDCl
3
): d 13.08 (─CH
), 52.94 (─CH N), 63.25
), 101.39 (C-8), 112.26
2 3
CH ),
1
(
(
(
3
), 20.79 (─CH CH
2
3
2
2
2
+
+
([M + H] ), calcd for [C H N O + H] 481.1718.
24 24 4 7
3-Ethyl-7-[2-hydroxy-3-(4-p-nitrophenoxymethyl-1,2,3-
1
triazol-1-yl)propyloxy]-4-methylcoumarin (15i). It was obtained
+
ꢀ
(ArC), 161.89 (CO); HR-ESI-TOF-MS m/z 514.0982 ([M + H] ),
as white solid in 86% yield; mp 148–150 C; IR (KBr): 3367, 2929,
+
À1
calcd for [C24
H
24BrN
3
O
5
+H] 514.0972.
2856, 1699, 1610, 1510, 1332, 1256, 1173, 1086, and 834 cm
H-NMR (400 MHz, DMSO-d ): d 1.04 (3H, t, J = 7.3 Hz,
;
1
3
-Ethyl-7-[2-hydroxy-3-(4-p-bromophenoxymethyl-1,2,3-
6
triazol-1-yl)propyloxy]-4-methylcoumarin (15f). It was obtained
─CH CH ), 2.39 (3H, s, C-4 CH ), 2.55 (2H, q, J = 7.3 Hz,
2
3
3
ꢀ
as white solid in 85% yield; mp 100–102 C; IR (KBr): 3402, 2922,
─CH
2
CH
3
), 4.00–4.10 (2H, m, ─CH
2
N), 4.22–4.29 (1H,
), 4.63 (1H,
dd, J = 13.9 and 3.8 Hz, ─OCH ), 5.33 (2H, s, ─CH OPh), 5.65
À1
2
859, 1717, 1610, 1490, 1387, 1251, 1171, 1091, and 823cm
;
m, ─CH), 4.48 (1H, dd, J = 13.9 and 7.3 Hz, ─OCH
a
1
H-NMR (400 MHz, CDCl ): d 1.13 (3H, t, J=7.7Hz, ─CH CH ),
3
2
3
b
2
2
.37 (3H, s, C-4 CH ), 2.65 (2H, q, J=7.3Hz, ─CH CH ), 3.88
(1H, d, J = 5.1 Hz, OH), 6.95–6.97 (2H, m, C-6H and C-8H),
7.26–7.28 (2H, m, ArH), 7.70 (1H, d, J = 8.8 Hz, C-5H),
3
2
3
(
1H, brs, OH), 4.03–4.10 (2H, m, ─CH
2
N), 4.51–4.60 (2H, m,
), 4.74 (1H, dd, J = 13.9 and 2.9 Hz,
), 5.14 (2H, s, ─CH OPh), 6.75 (1H, d, J = 2.9 Hz, C-
13
─
─
8
CH and ─OCH
OCH
a
8.18–8.23 (2H, m, ArH), 8.27 (1H, s, triazole H); C-NMR
(100 MHz, DMSO-d ): d 12.88 (─CH CH ), 14.24 (C-4 CH ),
20.15 (─CH CH ), 52.51 (─CH N), 61.83 (─OCH Ph), 67.54
b
2
6
2
3
3
H), 6.80–6.84 (3H, m, C-6H and ArH), 7.32–7.35 (2H, m,
2
3
2
2
ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s, triazole H);
(─CH), 69.99 (─OCH ), 100.95 (C-8), 112.20 (C-6), 113.80
2
1
3
C-NMR (100.6 MHz, CDCl
C-4 CH ), 20.74 (─CH CH
─OCH Ph), 68.29 (─CH), 69.26 (─OCH
12.14 (C-6), 113.41 (C-3), 114.73 (C-10), 116.45 (2-ArC),
3
): d 13.03 (─CH
), 53.00 (─CH
), 101.24 (C-8),
2
CH
3
), 14.51
(C-10), 115.21 (2-ArC), 123.77 (C-3) (CH═C), 125.75, 125.99
(3-ArC), 126.23 (C-5), 141.35 (CH═C), 146.32 (C-9), 152.95
(C-4), 160.30 (C-7), 160.68 (ArC), 163.23 (CO); HR-ESI-TOF-
(
(
1
1
1
3
2
3
2
N), 61.82
2
2
+
+
MS m/z 481.1703 ([M + H] ), calcd for [C H N O + H]
24 24 4 7
24.70 (CH═C), 125.08 (ArC), 125.50 (C-5), 132.22 (2-ArC),
481.1718.
43.42 (CH═C), 145.93 (C-9), 153.24 (C-4), 157.10 (C-7), 159.88
3-Ethyl-7-[2-hydroxy-3-(4-o-tolyloxymethyl-1,2,3-triazol-1-yl)
+
(
ArC), 161.94 (CO); HR-ESI-TOF-MS m/z 514.0965 ([M + H] ),
propyloxy]-4-methylcoumarin (15j). It was obtained as white
+
ꢀ
calcd for [C24H24BrN O
3 5
+H] 514.0972.
solid in 83% yield; mp 123–126 C; IR (KBr): 3385, 2922, 2852,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
À1
1
1
716, 1611, 1387, 1250, 1121, 1025, and 748 cm ; H-NMR
and OH), 4.01–4.05 (2H, m, ─CH N), 4.45–4.54 (2H, m,
2
(
400 MHz, CDCl ): d 1.12 (3H, t, J = 7.3 Hz, ─CH CH ), 2.28
─CH and ─OCH ), 4.68 (1H, dd, J= 11.9 and 2.9 Hz, ─OCH ),
3
2
3
a
b
(
─
(
(
3H, s, Ph-CH
CH CH
2H, m, ─CH
1H, dd, J = 13.9 and 3.8 Hz, ─OCH ), 5.14 (2H, s, ─CH OPh),
3
), 2.35 (3H, s, C-4 CH
), 3.85 (1H, d, J = 5.1 Hz, OH), 4.03–4.6
N), 4.47–4.57 (2H, m, ─CH and ─OCH ), 4.70
3
), 2.63 (2H, q, J = 7.3 Hz,
5.23 (2H, s, ─CH
(4H, m, C-6H and ArH), 6.98–7.00 (1H, m, ArH), 7.45 (1H,
d, J=8.8Hz, C-5H), 7.80 (1H, s, triazole H);
(100.6 MHz, CDCl ): d 13.03 (─CH CH ), 14.49 (C-4 CH ),
2
OPh), 6.74 (1H, d, J= 2.9Hz, C-8H), 6.79–6.94
2
3
13
2
a
C-NMR
b
2
3
2
3
3
6
7
.72–6.85 (5H, m, C-6H, C-8H, and 3-ArH), 7.13 (1H, m, ArH),
20.74 (─CH CH ), 52.94 (─CH N), 55.72 (Ph-OCH ), 62.82
2
3
2
3
13
.46 (1H, d, J = 8.7 Hz, C-5H), 7.77 (1H, s, triazole H); C-NMR
): d 13.02 (─CH CH ), 14.48 (Ph-CH ),
6.17 (C-4 CH ), 20.73 (─CH CH ), 52.94 (─CH N), 61.99
2 2
(─OCH Ph), 68.36 (─CH), 69.22 (─OCH ), 101.32 (C-8), 111.77
(
100.6MHz, CDCl
3
2
3
3
(C-6), 112.07 (C-3), 114.27 (ArC), 114.75 (C-10), 120.78 (ArC),
121.88 (CH═C), 124.78, 125.12 (2-ArC), 125.48 (C-5), 144.02
(ArC), 145.81 (CH═C), 147.42 (C-9), 149.49 (C-4), 153.31 (C-7),
159.92 (ArC), 161.91 (CO); HR-ESI-TOF-MS m/z 466.1978
1
3
2
3
2
(─OCH Ph), 68.32 (─CH), 69.24 (─OCH ), 101.29 (C-8),
2
2
1
11.35 (C-6), 112.11 (ArC), 114.74 (C-10), 120.93 (ArC and
+
+
CH═C), 124.30 (ArC), 125.10 (C-3), 125.49 (ArC), 126.84
C-5), 130.72 (ArC), 144.43 (CH═C), 145.87 (C-9), 153.29 (C-4),
([M + H] ), calcd for [C25
27 3 6
H N O +H] 466.1973.
(
3-Ethyl-7-[2-hydroxy-3-(4-m-methoxyphenoxymethyl-1,2,3-
1
4
56.20 (C-7), 159.94 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z
triazol-1-yl)propyloxy]-4-methylcoumarin (15n).
obtained as white solid in 86% yield; mp 90–93 C; IR (KBr):
It was
+
+
ꢀ
50.2010 ([M + H] ), calcd for [C H N O + H] 450.2023.
2
5 27 3 5
3
-Ethyl-7-[2-hydroxy-3-(4-m-tolyloxymethyl-1,2,3-triazol-1-yl)
3228, 2938, 2859, 1708, 1617, 1458, 1295, 1155, 1057, and
À1
1
propyloxy]-4-methylcoumarin (15 k). It was obtained as white
solid in 86% yield; mp 121–124 C; IR (KBr): 3511, 2924, 2852,
718, 1610, 1458, 1259, 1173, 1085, and 777 cm ; H-NMR
841 cm ; H-NMR (400 MHz, CDCl
─CH CH ), 2.37 (3H, s, C-4 CH ), 2.65 (2H, q, J=7.3Hz,
─CH CH ), 3.71 (1H, brs, OH), 3.77 (1H, s, Ph-OCH ), 4.03–
3
): d 1.14 (3H, t, J=7.3Hz,
ꢀ
2
3
3
À1
1
1
2
3
3
(
400 MHz, CDCl ): d 1.13 (3H, t, J = 7.4 Hz, ─CH CH ), 2.17
4.10 (2H, m, ─CH N), 4.50–4.59 (2H, m, ─CH and
3
2
3
2
(
─
3H, s, Ph-CH
CH CH
m, ─CH
dd, J = 13.9 and 3.7 Hz, ─OCH ), 5.18 (2H, s, ─CH OPh), 6.76–
3
), 2.36 (3H, s, C-4 CH
), 3.57 (d, 1H, J = 5.1 Hz, OH), 4.00–4.08 (2H,
N), 4.48–4.60 (2H, m, ─CH and ─OCH ), 4.72 (1H,
3
), 2.64 (2H, q, J = 8.1 Hz,
─OCH
(2H, s, ─CH
ArH), 6.77–6.85 (2H, m, ArH), 7.14–7.19 (1H, m, ArH), 7.48
a
), 4.72 (1H, dd, J= 12.4 and 2.2 Hz, ─OCH
b
), 5.16
2
3
2
OPh), 6.51–6.57 (3H, m, C-6H, C-8H, and
2
a
13
(1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); C-NMR
(100.6 MHz, CDCl ): d 13.04 (─CH CH ), 14.49 (C-4 CH ),
b
2
6
7
.92 (4H, m, C-6H, C-8H, and ArH), 7.09–7.14 (2H, m, ArH),
3
2
3
3
13
.47 (1H, d, J = 8.7 Hz, C-5H), 7.75 (1H, s, triazole H); C-NMR
): d 13.02 (─CH CH ), 14.48 (C-4 CH ),
0.72 (─CH CH ), 21.42 (Ph-CH ), 53.00 (─CH N), 61.58
2 3 2 3
20.75 (─CH CH ), 52.98 (─CH N), 55.21 (Ph-OCH ), 61.76
(
100.6MHz, CDCl
3
2
3
3
(─OCH Ph), 68.36 (─CH), 69.25 (─OCH ), 101.19 (C-8),
2 2
2
106.65 (C-6), 106.84 (C-3 and ArC), 112.11 (C-10), 114.77
(ArC), 124.58 (CH═C), 125.13, 125.51 (2-ArC), 129.92 (C-5),
143.84 (ArC), 145.87 (CH═C), 153.31 (C-9), 159.29 (C-4),
159.92 (C-7), 160.74 (ArC), 161.94 (CO); HR-ESI-TOF-MS m/z
2
3
3
2
(─OCH Ph), 68.31 (─CH), 69.27 (─OCH ), 101.28 (C-8),
2
2
1
(
1
1
4
11.43 (C-6), 112.13 (C-3 and ArC), 114.71 (C-10), 115.46
ArC), 122.05 (CH═C), 124.53, 125.06 (2-ArC), 129.17 (C-5),
+
+
39.52 (ArC), 143.99 (CH═C), 145.88 (C-9), 153.28 (C-4),
58.05 (C-7), 159.95 (ArC), 161.93 (CO); HR-ESI-TOF-MS m/z
466.1975 ([M + H] ), calcd for [C25
3-Ethyl-7-[2-hydroxy-3-(4-o-iodophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (15o). It was
27 3 6
H N O + H] 466.1973.
+
+
50.2023 ([M + H] ), calcd for [C H N O + H] 450.2023.
2
5 27 3 5
ꢀ
3
-Ethyl-7-[2-hydroxy-3-(4-p-tolyloxymethyl-1,2,3-triazol-1-yl)
obtained as white solid in 83% yield; mp 172–174 C; IR (KBr):
propyloxy]-4-methylcoumarin (15l). It was obtained as white
3273, 2932, 2873, 1711, 1617, 1439, 1297, 1155, 1061, and 760;
H-NMR (400MHz, CDCl ): d 1.13 (3H, t, J = 7.3 Hz,
3
ꢀ
1
solid in 84% yield; mp 127–130 C; IR (KBr): 3386, 2920, 2852,
À1
1
721, 1610, 1510, 1383, 1247, 1176, 1089, and 831 cm
;
─CH CH ), 2.37 (3H, s, C-4 CH ), 2.66 (2H, q, J = 7.3 Hz,
2 3 3
1
H-NMR (400MHz, CDCl3):
CH CH ), 2.26 (3H, s, Ph-CH
2H, q, J = 7.3Hz, ─CH CH
.01–4.08 (2H, m, ─CH N), 4.51–4.57 (2H, m, ─CH and
OCH ), 4.72 (1H, dd, J = 13.9 and 3.7 Hz, ─OCH ), 5.13
d
1.12 (3H, t, J = 7.3 Hz,
─CH CH ), 3.70 (1H, d, J = 5.2 Hz, OH), 4.03–4.08 (2H,
2 3
─
(
4
─
2
3
3
), 2.36 (3H, s, C-4 CH
3
), 2.64
m, ─CH
J= 13.2 and 2.9 Hz, ─OCH
2
N), 4.52–4.63 (1H, m, ─CH and ─OCH ), 4.74 (1H, dd,
2
), 5.25 (2H, s, ─CH OPh), 6.69–6.96
a
2
3
), 3.78 (1H, d, J = 5.1 Hz, OH),
b
2
(4H, m, C-6H, C-8H, and ArH), 7.25–7.30 (1H, m, ArH), 7.48 (1H,
d, J= 8.8 Hz, C-5H), 7.72–7.74 (1H, m, ArH), 7.89 (1H, s, triazole
a
b
13
(
2H, s, ─CH OPh), 6.75–6.85 (4H, m, C-6H, C-8H, and ArH),
H); C-NMR (100.6 MHz, CDCl ): d 13.02 (─CH CH ), 14.48 (C-
2
3 2 3
7
.03–7.06 (2H, m, ArH), 7.46 (1H, d, J = 8.7 Hz, C-5H), 7.78
4 CH
3
), 20.74 (─CH
2
CH
3
), 52.98 (─CH
2
), 101.28 (C-8), 115.70 (C-6), 115.74
2 2
N), 62.31 (─OCH Ph),
1
3
(
1H, s, triazole H); C-NMR (100.6MHZ, CDCl
3
): d 13.08
68.33 (─CH), 69.28 (─OCH
(
─CH CH ), 14.55 (C-4 CH ), 20.45 (─CH CH ), 20.79
(C-10), 115.93 (2-ArC), 125.13 (C-3), 125.50 (CH═C), 143.72
(ArC), 145.91 (C-5), 153.28 (2-ArC and CH═C), 154.13 (C-9),
156.23 (C-4), 158.62 (C-7), 159.92 (ArC), 161.95 (CO); HR-ESI-
2
3
3
2
3
(
Ph-CH ), 52.91 (─CH N), 61.89 (─OCH Ph), 68.51 (─CH),
3
2
2
6
2
9.17 (─OCH ), 101.46 (C-8), 111.97 (C-6), 114.54 (C-3 and
+
+
ArC), 114.91 (C-10), 124.44 (ArC), 125.31 (CH═C), 125.57,
TOF-MS m/z 562.0839 ([M + H] ), calcd for [C24
H
24IN
3
O
5
+H]
1
1
29.95 (3-ArC), 130.56 (C-5), 144.30 (CH═C), 145.76 (C-9),
562.0833.
53.38 (C-4), 155.96 (C-7), 159.86 (ArC), 161.91 (CO); HR-ESI-
3-Ethyl-7-[2-hydroxy-3-(4-p-iodophenoxymethyl-1,2,3-triazol-
1-yl)propyloxy]-4-methylcoumarin (15p).
white solid in 85% yield; mp 162–165 C; IR (KBr): 3384, 2922,
+
+
TOF-MS m/z 450.2023 ([M + H] ), calcd for [C H N O + H]
It was obtained as
2
5 27 3 5
ꢀ
4
50.2026.
-Ethyl-7-[2-hydroxy-3-(4-o-methoxyphenoxymethyl-1,2,3-
À1
3
2852, 1715, 1611, 1487, 1386, 1249, 1175, 1096, and 824 cm
;
1
triazol-1-yl)propyloxy]-4-methylcoumarin (15m).
obtained as white solid in 83% yield; mp 130–132 C; IR
It was
H-NMR (400 MHz, CDCl
3 2 3
): d 1.11 (3H, t, J=7.3Hz, ─CH CH ),
ꢀ
2.35 (3H, s, C-4 CH ), 2.62 (2H, q, J=7.3Hz, ─CH CH ), 3.78
3
2
3
(
KBr): 3401, 2963, 2859, 1674, 1605, 1508, 1387, 1254,
(1H, brs, OH), 4.00–4.08 (2H, m, ─CH N), 4.49–4.57 (2H, m,
2
À1
1
1
1
2
122, 1030, and 735 cm
.11 (3H, t, J = 7.7 Hz, ─CH
.62 (2H, q, J = 8.1 Hz, ─CH
;
H-NMR (400 MHz, CDCl
CH ), 2.35 (3H, s, C-4 CH
CH ), 3.80 (4H, m, Ph-OCH
3
): d
─CH and ─OCH
5.11 (2H, s, ─CH
ArH), 7.44–7.51 (3H, m, ArH and C-5H), 7.78 (1H, s, triazole H);
a
), 4.71 (1H, dd, J= 13.2 and 3.7 Hz, ─OCH
b
),
2
3
3
),
2
OPh), 6.68–6.82 (4H, m, C-6H, C-8H, and
2
3
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
1
3
C-NMR (100.6 MHz, CDCl ): d 13.05 (─CH CH ), 14.55 (C-4
(C-3), 125.47 (CH═C), 126.57 (C-5), 126.70 (3-ArC), 128.05
(3-ArC), 128.67 (2-ArC), 140.39 (ArC), 143.79 (CH═C), 145.89
(C-9), 153.26 (C-4), 157.58 (C-7), 159.91 (ArC), 161.93
3
2
3
CH ), 20.76 (─CH CH ), 53.00 (─CH N), 61.72 (─OCH Ph),
6
1
3
2
3
2
2
8.32 (─CH), 69.27 (─OCH
14.78 (C-10), 117.05 (2-ArC and C-3), 124.69 (CH═C), 125.14
2
), 101.28 (C-8), 112.13 (C-6),
+
(CO); HR-ESI-TOF-MS m/z 512.2171 ([M + H] ), calcd for
+
(ArC), 125.52 (C-5), 138.20 (2-ArC and CH═C), 145.91 (C-9),
[C30H N O
29 3 5
+ H] 512.2180.
1
53.27 (C-4), 157.89 (C-7), 159.87 (ArC), 161.94 (CO); HR-ESI-
3-Ethyl-7-[2-hydroxy-3-(4-(naphthalen-2-loxymethyl)-1,2,3-
+
+
TOF-MS m/z 562.0839 ([M + H] ), calcd for [C H IN O + H]
5
triazol-1-yl)propyloxy]-4-methylcoumarin (15t). It was obtained
2
4
24
3 5
ꢀ
62.0833.
-Ethyl-7-[2-hydroxy-3-(4-m-fluorophenoxymethyl-1,2,3-
as white solid in 89% yield; mp 142–146 C; IR (KBr): 3161, 2925,
À1
1
3
2856, 1718, 1621, 1466, 1294, 1182, 1084, and 845cm ; H-
triazol-1-yl)propyloxy]-4-methylcoumarin (15q). It was obtained
NMR (400MHz, CDCl ): d 1.11 (3H, t, J=7.3Hz, ─CH CH ),
3
2
3
ꢀ
as white solid in 87% yield; mp 120–122 C; IR (KBr): 3392, 2935,
2.33 (3H, s, C-4 CH ), 2.62 (2H, q, J = 7.3 Hz, ─CH CH ), 3.62
3
2
3
À1
1
2
875, 1706, 1616, 1490, 1298, 1160, 1070, and 840 cm ; H-
NMR (400 MHz, CDCl ): d 1.11 (3H, t, J = 7.7 Hz, ─CH CH ),
.35 (3H, s, C-4 CH ), 2.62 (2H, q, J = 7.3 Hz, ─CH CH ), 3.64
2
(1H, d, J = 5.12 Hz, OH), 4.00–4.07 (2H, m, ─CH N), 4.48–4.57
3
2
3
(2H, m, ─CH and ─OCH
a
), 4.70 (1H, dd, J = 13.7 and 2.8 Hz,
OPh), 6.74 (1H, d, J = 2.2 Hz, C-
2
3
2
3
─OCH ), 5.28 (2H, s, ─CH
b
2
(
(
1H, d, J = 5.1Hz, OH), 4.00–4.07 (2H, m, ─CH N), 4.48–4.58
8H), 6.79 (1H, dd, J = 2.2 and 8.8Hz, C-6H), 7.10–7.22 (2H, m,
ArH), 7.29–7.44 (3H, m, ArH), 7.68–7.73 (3H, m, C-5H and ArH),
2
2H, m, ─CH and ─OCH ), 4.71 (1H, dd, J = 13.2 and 2.9 Hz,
a
13
─
OCH
b
2
), 5.14 (2H, s, ─CH OPh), 6.62–6.70 (2H, m, C-6H and
7.81 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl
(─CH CH ), 14.43 (C-4 CH ), 20.72 (─CH CH ), 53.03 (─CH
61.66 (─OCH Ph), 68.31 (─CH), 69.27 (─OCH ), 101.24 (C-8),
3
): d 13.02
C-8H), 6.71–6.82 (3H, m, ArH), 7.16–7.21 (1H, m, ArH), 7.46
2
3
3
2
3
2
N),
13
(
(
1H, d, J = 8.8 Hz, C-5H), 7.79 (1H, s, triazole H); C-NMR
100.6MHz, CDCl ): d 13.02 (─CH CH ), 14.48 (C-4 CH ),
2
2
107.02 (ArC), 112.08 (C-6), 114.67 (C-10), 118.59 (ArC), 123.82
(C-3), 124.70 (ArC), 125.44 (CH═C), 127.52 (ArC), 129.46 (ArC),
143.71 (ArC), 145.88 (CH═C), 153.23 (C-4), 155.94 (C-9), 159.89
3
2
3
3
2
0.73 (─CH CH ), 53.01 (─CH N), 61.89 (─OCH Ph), 68.31
2 3 2 2
(─CH), 69.27 (─OCH
2
), 101.27 (C-8), 102.41 (C-6), 102.66 (C-
), 107.96 (C-10), 108.17, 110.26 (2-ArC), 112.16 (CH═C),
14.74 (ArC), 124.71 (C-5), 125.50, 130.21 (2-ArC), 145.95
+
3
1
(C-7), 161.93 (CO); HR-ESI-TOF-MS m/z 486.2021 ([M + H] ),
+
calcd for [C28H N O
27 3 5
+ H] 486.2023.
(
(
CH═C), 153.26 (C-9), 159.30 (C-4), 159.92 (C-7), 161.97
3-Ethyl-7-[2-hydroxy-3-(4-(naphthalen-1-loxymethyl)-1,2,3-
+
ArC), 164.65 (CO); HR-ESI-TOF-MS m/z 454.1773 ([M + H] ),
triazol-1-yl)propyloxy]-4-methylcoumarin (15u). It was obtained
+
ꢀ
calcd for [C24
H24FN O
3 5
+ H] 454.1773.
as white solid in 90% yield; mp 110–113 C; IR (KBr): 3374, 2932,
À1
1
3
-Ethyl-7-[2-hydroxy-3-(4-p-fluorophenoxymethyl-1,2,3-
2872, 1698, 1608, 1389, 1268, 1151, 1097, and 771cm ; H-
triazol-1-yl)propyloxy]-4-methylcoumarin (15r). It was obtained
NMR (400MHz, CDCl ): d 1.11 (3H, t, J = 7.3 Hz, ─CH CH ),
3
2
3
ꢀ
as white solid in 85% yield; mp 126–129 C; IR (KBr): 3384, 2963,
2.31 (3H, s, C-4 CH ), 2.62 (2H, q, J = 7.3Hz, ─CH CH ), 3.76
3
2
3
À1
2
873, 1705, 1616, 1510, 1298, 1159, 1095, and 822cm
;
(1H, brs, OH), 3.99–4.06 (2H, m, ─CH
2
N), 4.52–4.58 (1H, m,
─CH and ─OCH ),
2
5.34 (2H, s, ─CH OPh), 6.72 (1H, d, J= 2.9 Hz, C-8H), 6.78
1
H-NMR (400 MHz, CDCl
.37 (3H, s, C-4 CH ), 2.65 (2H, q, J=7.4Hz, ─CH
1H, d, J=4.4Hz, OH), 4.02–4.10 (2H, m, ─CH N), 4.52–4.60
3
): d 1.13 (3H, t, J=7.4Hz, ─CH
2
3
CH ),
a b
), 4.70 (1H, dd, J = 13.9 and 3.7 Hz, ─OCH
2
(
3
2
CH ), 3.67
3
(1H, dd, J= 2.2 and 8.8 Hz, C-6H), 6.89 (1H, d, J = 7.3 Hz, ArH),
7.28–7.46 (5H, m, ArH), 7.75 (1H, d, J= 8.1 Hz, C-5H), 7.83
2
(
2H, m, ─CH and ─OCH ), 4.74 (1H, dd, J=13.2 and
a
13
2
.9 Hz, ─OCH
b
2
), 5.15 (2H, s, ─CH OPh), 6.76 (1H, d, J=2.2Hz,
(1H, s, triazole), 8.15 (1H, d, J = 8.8 Hz, ArH); C-NMR
(100.6 MHz, CDCl ): d 13.02 (─CH CH ), 14.43 (C-4 CH ),
20.72 (─CH CH ), 53.01 (─CH N), 62.07 (─CH), 68.32
(─OCH ), 69.25 (─OCH Ph), 101.23 (C-8), 105.20 (ArC), 112.08
C-8H), 6.83 (1H, dd, J= 2.9 and 8.8 Hz, C-6H), 6.87–6.97 (4H,
m, ArH), 7.48 (1H, d, J= 8.8Hz, C-5H), 7.80 (1H, s, triazole H);
3
2
3
3
2
3
2
13
C-NMR (100.6 MHz, CDCl ): d 13.02 (─CH CH ), 14.81 (C-4
3
2
3
2
2
CH ), 20.74 (─CH CH ), 52.98 (─CH N), 62.31 (─OCH Ph),
(C-6), 114.68 (C-10), 120.79 (C-3), 121.81, 124.56, 125.04 (3-
ArC), 125.18 (C-5), 125.45, 125.69 (3-ArC), 126.38 (CH═C),
127.39, 134.38 (2-ArC), 143.99 (CH═C), 145.89 (C-4), 153.23
(C-9), 153.72 (ArC), 159.88 (C-7), 161.95 (CO); HR-ESI-TOF-
3
2
3
2
2
2
68.33 (─CH), 69.28 (─OCH ), 101.29 (C-8), 112.15 (C-6),
114.77 (C-3), 115.70 (C-10), 115.74, 115.82 (2-ArC), 115.93
(CH═C), 125.13 (ArC), 125.50 (C-5), 143.72, 145.91 (2-ArC),
+
+
1
1
53.28 (CH═C), 154.13 (C-9), 156.23 (C-4), 158.62 (C-7),
59.91 (ArC), 161.95 (CO); HR-ESI-TOF-MS m/z 454.1783
MS m/z 486.2018 ([M + H] ), calcd for [C H N O +H]
28 27 3 5
486.2023.
+
+
([M + H] ), calcd for [C24
H24FN O
3 5
+ H] 454.1773.
3-Hexyl-7-[2-hydroxy-3-(4-phenoxymethyl-1,2,3-triazol-1-yl)
3
-Ethyl-7-[2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-
propyloxy]-4-methylcoumarin (16a). It was obtained as white
ꢀ
triazol-1-yl)propyloxy]-4-methylcoumarin (15s).
obtained as white solid in 89% yield; mp 128–131 C; IR
KBr): 3421, 2925, 2856, 1707, 1609, 1387, 1251, 1177,
It was
solid in 85% yield; mp 101–104 C; IR (KBr): 3385, 2920, 2851,
ꢀ
À1
1
1717, 1611, 1387, 1260, 1172, 1026, and 770 cm ; H-NMR
(400 MHz, CDCl ): d 0.89 (3H, t, J = 7.0 Hz, ─(CH CH ),
1.25–1.40 (6H, m, ─CH CH (CH CH ), 1.46–1.52 (2H,
m, ─CH CH (CH CH ), 2.37 (3H, s, C-4 CH ), 2.61
(2H, t, J=7.3Hz, ─CH (CH ) CH ), 4.02–4.09 (2H, m, ─CH N),
(
1
(
(
3
2
)
5
3
À1
1
085, and 761 cm
;
H-NMR (400 MHz, CDCl
CH ), 2.33 (3H, s, C-4 CH
2H, q, J = 7.3 Hz, ─CH CH ), 3.61 (1H, d, J = 4.5 Hz, OH),
3
): d 1.10
2
2
2
)
3
3
3H, t, J = 7.6 Hz, ─CH
2
3
3
), 2.62
2
2
2
)
3
3
3
2
3
2
2 4
3
2
4
.00–4.08 (2H, m, ─CH N), 4.50–4.58 (2H, m, ─CH and
4.47–4.59 (2H, m, ─CH and ─OCH ), 4.72 (1H, dd, J= 13.9 and
2
a
─
(
(
OCH
2H, s, ─CH
1H, dd, J = 2.8 and 8.7 Hz, C-6H), 6.99–7.02 (2H, m, ArH),
a
), 4.70 (1H, dd, J = 13.7 and 2.8 Hz, ─OCH
b
), 5.21
b 2
3.7 Hz, ─OCH ), 5.19 (2H, s, ─CH OPh), 6.78 (1H, d, J=2.9Hz,
2
OPh), 6.75 (1H, d, J = 2.3 Hz, C-8H), 6.80
C-8H), 6.83 (1H, dd, J = 8.8 and 1.5 Hz, C-6H), 6.94–6.96 (3H, m,
ArH), 7.25–7.30 (2H, t, J= 8.8 Hz, ArH), 7.47 (1H, d, J=8.7Hz,
13
7
.26–7.52 (8H, m, C-5H and ArH), 7.80 (1H, s, triazole H);
C-NMR (100.6 MH , CDCl ): d 13.02 (─CH CH ), 14.45
C-5H), 7.79 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl ): d
3
1
3
14.05 (─(CH ) CH ), 14.79 (C-4 CH ), 16.19 (─CH (CH )
Z
3
2
3
2 5
3
3
2
2
(
(
1
C-4 CH
─OCH
12.11 (C-6), 114.71 (C-10), 114.93 (2-ArC), 124.66
3
), 20.72 (─CH
Ph), 68.31 (─CH), 69.28 (─OCH
2
CH
3
), 53.03 (─CH
2
N), 61.75
3
CH
(CH
CH
2
CH
3
), 22.59 (─CH
3
2
(CH
), 29.34 (─CH CH
N), 62.03 (─CH), 68.38 (─OCH
2
)
3
CH
(CH
2
CH
3
2 2
), 27.49 (─CH CH
2
2
), 101.28 (C-8),
2
3
) CH
2
2
2 3 3 2
) CH ), 31.65 (─(CH )
3
CH
2 2
3
CH ), 52.94 (─CH
2
2
),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
6
9.24 (─OCH Ph), 101.33 (C-8), 111.39 (C-6 and C-10), 112.06 (2-
C-6H), 6.85–6.89 (2H, m, ArH), 7.17–7.21 (2H, m, ArH), 7.47
2
13
ArC), 114.82 (ArC), 120.95 (C-3), 124.09 (C-5), 126.78 (CH═C),
26.86, 130.75 (2-ArC), 144.49 (CH═C), 146.00 (C-4), 153.33
C-9), 156.22 (ArC), 159.89 (C-7), 162.06 (CO); HR-ESI-TOF-
(1H, d, J = 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); C-NMR
(100.6 MHz, CDCl ): d 14.05 (─(CH CH ), 14.80 (C-4 CH ),
21.46 (─CH (CH CH CH ), 22.59 (─CH (CH CH CH ), 28.74
(─CH CH (CH CH ), 29.35 (─(CH CH (CH CH ), 31.66
(─(CH ) CH CH CH ), 53.00 (─CH N), 61.66 (─CH), 68.38
1
(
3
)
2 5
3
3
2
2
)
3
2
3
2
2
)
3
2
3
+
+
MS m/z 492.2493 ([M + H] ), calcd for [C28
92.2493.
-Hexyl-7-[2-hydroxy-3-(4-o-chlorophenoxymethyl-1,2,3-
H N O
33 3 5
+H]
2
2
2
)
3
3
2
)
2
2
2
)
2
3
4
2
3
2
2
3
2
3
(─OCH ), 69.26 (─OCH Ph), 101.35 (C-8), 111.48 (C-6), 112.11
2 2
triazol-1-yl)propyloxy]-4-methylcoumarin (16b). It was obtained
(C-10), 115.52 (3-ArC), 122.09 (C-3), 124.52 (C-5), 125.52
(CH═C), 129.21 (2-ArC), 139.59 (CH═C), 146.02 (ArC), 153.33
(C-4), 158.09 (C-9), 159.92 (C-7), 162.06 (CO); HR-ESI-TOF-MS
ꢀ
as white solid in 92% yield; mp 134–138 C; IR (KBr): 3392, 2926,
À1 1
2
872, 1718, 1617, 1458, 1280, 1170, 1087, and 759 cm ; H-NMR
+
+
(
400 MHz, CDCl ): d 0.89 (3H, t, J=7.3Hz, ─(CH ) CH ),
m/z 526.2103 ([M + H] ), calcd for [C H ClN O +H] 526.2103.
3
2 5
3
28 32 3 5
1
.25–1.40 (6H, m, ─CH
CH (CH CH ), 2.36 (3H, s, C-4 CH
d, J=7.3Hz, ─CH (CH CH ), 3.75 (1H, brs, OH), 4.04–4.09
2H, m, ─CH N), 4.53–4.60 (2H, m, ─CH and ─OCH ), 4.74
2
CH
2
(CH
2
)
3
CH
3
), 1.45–1.54 (2H,
3-Hexyl-7-[2-hydroxy-3-(4-o-bromophenoxymethyl-1,2,3-
m, ─CH
2
2
2
)
3
3
3
), 2.61 (2H,
triazol-1-yl)propyloxy]-4-methylcoumarin (16e). It was obtained
ꢀ
2
2
)
4
3
as white solid in 91% yield; mp 129–133 C; IR (KBr): 3232, 2925,
À1
1
(
2853, 1718, 1621, 1487, 1297, 1170, 1087, and 757cm ; H-
2
a
(
1H, dd, J= 13.2 and 2.9 Hz, ─OCH ), 5.26 (2H, s, ─CH OPh),
NMR (400MHz, CDCl ): d 0.89 (3H, t, J = 7.3 Hz, ─(CH )
b
2
3
2
6
.76 (1H, d, J= 2.9 Hz, C-8H), 6.84 (1H, dd, J = 8.8 and 2.2 Hz,
5
CH
(2H, m, ─CH
(2H, t, J = 8.1 Hz, ─CH
3
), 1.25–1.40 (6H, m, ─CH
CH (CH CH
(CH
2
CH
2
(CH
2
)
3
CH
3
), 1.46–1.54
C-6H), 6.87–7.34 (4H, m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H),
2
2
2
)
3
3
), 2.36 (3H, s, C-4 CH
3
), 2.61
1
3
7
.85 (1H, s, triazole H); C-NMR (100.6MHz, CDCl
3
): d 14.03
2
)
2 4
CH ), 3.80 (1H, brs, OH),
3
(
─(CH ) CH ), 14.77 (C-4 CH ), 22.57 (─CH (CH ) CH CH ),
4.03–4.09 (2H, m, ─CH N), 4.53–4.61 (2H, m, ─CH and
2
5
3
3
2
2 3
2
3
2
2
7.46 (─CH (CH ) CH CH ), 28.69 (─CH CH (CH ) CH ), 29.32
─OCH ), 4.73 (1H, dd, J = 13.2 and 2.9 Hz, ─OCH ), 5.26
2
2 3
2
3
2
2
2 3
3
a
b
(
(
1
─(CH
─CH
01.23 (C-8), 112.13 (C-6), 114.07 (C-10), 114.73, 122.03, 122.92
2
)
2
CH
2
(CH
2
)
2
CH
3
), 31.62 (─(CH
2
)
3
CH
2
CH
2
CH
3
), 53.03
(2H, s, ─CH
2
OPh), 6.77 (1H, d, J = 2.9 Hz, C-8H), 6.81–6.86
2
N), 62.97 (─CH), 68.29 (─OCH
2
), 69.23 (─OCH
2
Ph),
(2H, m, C-6H, ArH), 7.03 (1H, dd, J = 8.1 and 1.5 Hz, ArH),
7.21–7.27 (1H, m, ArH), 7.46–7.51 (2H, m, ArH and C-5H), 7.86
(1H, s triazole H); C-NMR (100.6 MHz, CDCl ): d 14.04
13
(3-ArC), 123.97 (C-3), 124.70 (C-5), 125.48 (CH═C), 127.74 (2-
3
ArC), 130.24 (CH═C), 146.06 (C-4), 153.27 (C-9), 153.54 (ArC),
(─(CH ) CH ), 14.79 (C-4 CH ), 22.58 (─CH (CH ) CH CH ),
2
5
3
3
2
2 3
2
3
1
59.89 (C-7), 162.07 (CO); HR-ESI-TOF-MS m/z 526.2109
27.49 (─CH
31.64 (─(CH
68.36 (─OCH ), 69.19 (─OCH Ph), 101.30 (C-8), 112.09 (C-6
2 2 2 3 3 2 2 2 2 2 3
CH (CH ) CH ), 29.33 (─(CH ) CH (CH ) CH ),
+
+
([M + H] ), calcd for [C28
H
32ClN
3
O
5
+H] 526.2103.
2 3 2 2 3 2
) CH CH CH ), 53.00 (─CH N), 63.18 (─CH),
3
-Hexyl-7-[2-hydroxy-3-(4-m-chlorophenoxymethyl-1,2,3-
2
2
triazol-1-yl)propyloxy]-4-methylcoumarin (16c).
obtained as white solid in 85% yield; mp 100–102 C; IR
It was
and ArC), 112.23 (C-10), 113.89 (ArC), 114.81 (C-3), 122.54
(ArC), 124.08 (C-5), 124.61 (CH═C), 125.52, 128.52 (2-ArC),
133.32 (CH═C), 145.99 (C-4), 153.32 (C-9), 154.40 (ArC),
159.87 (C-7), 162.04 (CO); HR-ESI-TOF-MS m/z 570.1603
ꢀ
(
1
KBr): 3393, 2927, 2855, 1705, 1616, 1383, 1298, 1159,
087, and 768 cm ; H-NMR (400 MHz, CDCl ): d 0.89
3
À1
1
+
+
(
(
(
3H, t, J = 6.6 Hz, ─(CH ) CH ), 1.26–1.38 (6H, m, ─CH CH
([M + H] ), calcd for [C H BrN O + H] 570.1598.
2
5
3
2
2
28 32 3 5
CH ) CH ), 1.46–1.52 (2H, m, ─CH CH (CH ) CH ), 2.37
3-Hexyl-7-[2-hydroxy-3-(4-p-bromophenoxymethyl-1,2,3-
2
3
3
2
2
2 3
3
3H, s, C-4 CH
.75 (1H, brs, OH), 4.03–4.09 (2H, m, ─CH
m, ─CH and ─OCH ), 4.73 (1H, dd, J = 13.9 and 3.7 Hz,
OCH ), 5.16 (2H, s, ─CH OPh), 6.76–6.95 (5H, m, C-6H,
3
), 2.61 (2H, d, J = 7.7 Hz, ─CH
2
(CH
2 4 3
) CH ),
triazol-1-yl)propyloxy]-4-methylcoumarin (16f).
obtained as white solid in 85% yield; mp 99–101 C; IR (KBr):
It was
ꢀ
3
2
N), 4.53–4.60 (2H,
a
3402, 2922, 2855, 1717, 1610, 1387, 1251, 1171, 1091, and
À1
1
─
823 cm ; H-NMR (400 MHz, CDCl ): d 0.89 (3H, t, J = 7.3 Hz,
b
2
3
C-8H, and ArH), 7.15 (1H, t, J = 8.1 Hz, ArH), 7.48 (1H, d,
─(CH ) CH ), 1.25–1.44 (6H, m, ─CH CH (CH ) CH ),
2
5
3
2
2
2 3
3
13
J = 8.8 Hz, C-5H), 7.81 (1H, s, triazole H);
100.6MHz, CDCl ): d 14.05 (─(CH CH ), 14.81 (C-4 CH
2.59 (─CH (CH CH CH ), 27.49 (─CH (CH CH CH ), 28.72
─CH CH (CH ) CH ), 29.34 (─(CH ) CH (CH ) CH ), 31.65
C-NMR
1.48–1.54 (2H, m, ─CH
CH ), 2.61 (2H, t, J = 8.1 Hz, ─CH
J = 4.4Hz, OH), 4.02–4.09 (2H, m, ─CH
─CH and ─OCH ), 4.74 (1H, dd, J = 13.9 and 2.9 Hz, ─OCH ),
2
CH
2
(CH
2
)
3
CH
(CH
3
), 2.37 (3H, s, C-4
CH ), 3.76 (1H, d,
N), 4.50–4.59 (2H, m,
(
3
)
2 5
3
3
),
3
2
2
)
4
3
2
2
2
)
3
2
3
2
2
)
3
2
3
2
(
2
2
2 3
3
2 2
2
2 2
3
a
b
(
─(CH ) CH CH CH ), 52.99 (─CH N), 61.89 (─CH),
5.15 (2H, s, ─CH OPh), 6.75 (1H, d, J = 2.9 Hz, C-8H), 6.80–6.85
2
3
2
2
3
2
2
6
(
1
(
8.37 (─OCH
C-6), 112.97 (C-10), 114.83, 115.24, 121.44 (3-ArC), 124.10 (C-3),
24.65 (C-5), 125.53 (CH═C), 130.26, 134.84 (2-ArC), 143.39
CH═C), 146.01 (C-4), 153.31 (C-9), 158.75 (C-7), 159.85 (ArC),
2
), 69.24 (─OCH
2
Ph), 101.31 (C-8), 112.08
(3H, m, C-6H and ArH), 7.33–7.36 (2H, m, ArH), 7.47 (1H, d,
13
J= 8.8 Hz, C-5H), 7.80 (1H, s, triazole H); C-NMR (100.6 MHz,
CDCl ): d 14.03 (─(CH ) CH ), 14.79 (C-4 CH ), 22.57 (─CH
3
2 5
3
3
2
(CH ) CH CH ), 27.46 (─CH CH (CH ) CH ), 29.32 (─(CH )
2 3 2 3 2 2 2 3 3 2
+
162.06 (CO); HR-ESI-TOF-MS m/z 526.2106 ([M + H] ), calcd for
2
CH
2
(CH
2
)
2
CH
3
), 31.62 (─(CH ), 53.01 (─CH
2
)
3
CH
2
CH
2
CH
3
2
N),
+
[C
28
H
32ClN
3
O
5
+H] 526.2103.
61.83 (─CH), 68.29 (─OCH
2
), 69.27 (─OCH Ph), 101.23 (C-8),
2
3
-Hexyl-7-[2-hydroxy-3-(4-p-chlorophenoxymethyl-1,2,3-
112.13 (C-6), 113.42 (C-10), 114.76, 116.46 (3-ArC), 123.99 (C-
3), 124.70 (C-5), 125.50 (CH═C), 132.22 (2-ArC), 143.41
(CH═C), 146.09 (C-4), 153.24 (C-9), 157.10 (ArC), 159.86 (C-7),
triazol-1-yl)propyloxy]-4-methylcoumarin (16d). It was obtained
as white solid in 81% yield; mp 122–126 C; IR (KBr): 3392, 2922,
853, 1718, 1611, 1387, 1250, 1091, and 825cm ; H-NMR
400MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH CH ),
.23–1.40 (6H, m, ─CH CH (CH CH ), 1.45–1.54 (2H, m,
CH CH (CH ) CH ), 2.37 (3H, s, C-4 CH ), 2.61 (2H, t,
ꢀ
À1
1
+
2
(
1
─
162.08 (CO); HR-ESI-TOF-MS m/z 570.1598 ([M + H] ), calcd for
+
3
)
2 5
3
[C28
H
32BrN
3
O
5
+H] 570.1598.
2
2
)
2 3
3
3-Hexyl-7-[2-hydroxy-3-(4-o-nitrophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (16g). It was obtained
2
2
2 3
3
3
ꢀ
J = 7.3 Hz, ─CH (CH ) CH ), 3.71 (1H, brs, OH), 4.02–4.10
as white solid in 85% yield; mp 130–133 C; IR (KBr): 3419, 2924,
2
2 4
3
À1
1
(
(
6
2H, m, ─CH
1H, dd, J = 13.9 and 2.2 Hz, ─OCH
.75 (1H, d, J = 2.9Hz, C-8H), 6.81 (1H, dd, J = 9.5 and 2.9 Hz,
2
N), 4.51–4.60 (2H, m, ─CH and ─OCH
a
), 4.74
2856, 1689, 1612, 1347, 1255, 1163, 1090, and 739cm ; H-
NMR (400 MHz, DMSO-d ): d 0.84 (3H, t, J=7.3Hz, ─(CH
CH ), 1.23–1.40 (6H, m, ─CH CH (CH CH ), 1.45–1.52 (2H,
b
), 5.15 (2H, s, ─CH
2
OPh),
6
2
)
5
3
2
2
2
)
3
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
m, ─CH CH (CH ) CH ), 2.37 (3H, s, C-4 CH ), 2.61 (2H, t,
3-Hexyl-7-[2-hydroxy-3-(4-o-tolyloxymethyl-1,2,3-triazol-1-yl)
2
2
2 3
3
3
J=8.1Hz, ─CH (CH ) CH ), 4.01–4.10 (2H, m, ─CH N), 4.22–
propyloxy]-4-methylcoumarin (16j). It was obtained as white
2
2 4
3
2
ꢀ
4
4
─
.30 (1H, m, ─CH), 4.48 (1H, dd, J= 13.9 and 7.3 Hz, ─OCH
.60 (1H, dd, J= 13.9 and 3.7 Hz, ─OCH ), 5.35 (2H, s,
CH OPh), 5.64 (1H, d, J=5.12Hz, OH), 6.93–6.96 (2H, m, C-
H and C-6H), 7.09–7.14 (1H, m, ArH), 7.57–7.70 (3H, m, ArH),
a
),
solid in 83% yield; mp 120–122 C; IR (KBr): 3385, 2922, 2852,
À1
1
b
1716, 1611, 1387, 1250, 1121, 1025, and 748 cm ; H-NMR
(400 MHz, CDCl ): d 0.86 (3H, t, J = 7.3 Hz, ─(CH CH ),
1.23–1.40 (6H, m, ─CH CH (CH ) CH ), 1.45–1.52 (2H, m,
2
3
)
2 5
3
8
7
2
2
2 3
3
1
3
.85 (1H, d, J=8.1Hz, C-5H), 8.21 (1H, s, triazole H); C-
): d 14.01 (─(CH CH ), 14.68 (C-
CH CH ), 26.86 (─CH CH (CH
3CH3), 28.71 (─(CH ) CH (CH ) CH ), 31.67 (─(CH2)
─CH CH (CH ) CH ), 2.18 (3H, s, Ph-CH ), 2.36 (3H, s, C-4
2 2 2 3 3 3
NMR (100.6 MHz, DMSO-d
CH ), 22.13 (─CH (CH
6
)
2 5
3
CH
J = 5.1 Hz, OH), 4.05–4.09 (2H, m, ─CH
─CH and ─OCH ), 4.71 (1H, dd, J = 13.9 and 3.7 Hz, ─OCH ),
3
), 2.61 (2H, t, J = 8.1 Hz, ─CH
2
(CH
2
)
4
CH
3
), 3.87 (1H, d,
4
3
2
)
2 3
2
3
2
2
2
)
2
N), 4.54–4.60 (2H, m,
2 2
2
2 2
3
a
b
CH CH CH ), 52.61 (─CH N), 62.58 (─CH), 67.67 (─OCH ),
5.19 (2H, s, ─CH OPh), 6.75–6.92 (4H, m, C-8H, C-6H, and
3
2
2
3
2
2
2
7
2
0.10 (─OCH Ph), 101.04 (C-8), 112.38 (C-6), 113.92 (C-10),
ArH), 7.10–7.15 (2H, m, ArH), 7.47 (1H, d, J= 8.7 Hz, C-5H), 7.78
13
1
15.61, 120.95 (2-ArC), 122.65 (C-3), 124.99 (C-5), 125.99
(1H, s, triazole H); C-NMR (100.6 MHz, CDCl
(─(CH CH ), 14.79 (Ph-CH ), 20.41 (C-4 CH ), 22.59 (─CH
(CH ) CH CH ), 27.49 (─CH CH (CH ) CH ), 29.34 (─(CH )
3
): d 14.04
(
(
ArC), 126.39 (CH═C), 134.38, 139.77 (2-ArC), 141.56
2
)
5
3
3
3
2
CH═C), 146.76 (C-4), 150.66 (C-9), 153.08 (ArC), 160.44 (C-
2
3
2
3
2
2
2 3
3
2
+
7
), 161.01 (CO); HR-ESI-TOF-MS m/z 537.2346 ([M + H] ),
CH (CH ) CH ), 31.65 (─(CH ) CH CH CH ), 52.97 (─CH N),
2 2 2 2 3 2 3 2 2 3 2
+
calcd for [C28
H N O
32 4 7
+ H] 537.2344.
2 2
61.85 (─CH), 68.39 (─OCH ), 69.25 (─OCH Ph), 101.36 (C-8),
3
-Hexyl-7-[2-hydroxy-3-(4-m-nitrophenoxymethyl-1,2,3-
112.07 (C-6), 114.53 (ArC), 114.81 (C-10), 124.08 (ArC), 124.49 (C-
3), 125.51 (C-5), 129.91 (2-ArC), 130.52 (CH═C and ArC), 144.15
(CH═C), 145.98 (C-4), 153.33 (C-9), 155.96 (ArC), 159.89 (C-7),
triazol-1-yl)propyloxy]-4-methylcoumarin (16h). It was obtained
as white solid in 88% yield; mp 136–140 C; IR (KBr): 3222, 2928,
858, 1717, 1618, 1349, 1252, 1162, 1083, and 826 cm ; H-
NMR (400 MHz, DMSO-d ): d 0.84 (3H, t, J = 7.3 Hz, ─(CH
CH ), 1.26–1.33 (6H, m, ─CH CH (CH CH ), 1.38–1.43
2H, m, ─CH
ꢀ
À1
1
+
2
162.05 (CO); HR-ESI-TOF-MS m/z 506.2653 ([M + H] ), calcd for
+
6
2
)
[C29
H
35
N
3
O
5
+H] 506.2649.
5
3
2
2
)
2 3
3
3-Hexyl-7-[2-hydroxy-3-(4-m-tolyloxymethyl-1,2,3-triazol-1-yl)
(
2
4
2 2 2 3 3 3
CH (CH ) CH ), 2.37 (3H, s, C-4 CH ), 2.49–
propyloxy]-4-methylcoumarin (16k). It was obtained as white
ꢀ
.54 (2H, m, ─CH (CH ) CH ), 3.99–4.07 (2H, m, ─CH N),
solid in 86% yield; mp 99–102 C; IR (KBr): 3511, 2924, 2852,
2
2 4
3
2
À1
1
.21–4.28 (2H, m, ─CH), 4.45 (1H, dd, J = 13.2 and 3.7 Hz,
OCH ), 4.61 (1H, dd, J = 13.8 and 3.2 Hz, ─OCH ), 5.29 (2H,
s, ─CH OPh), 5.65 (1H, d, J = 5.1 Hz, OH), 6.93–6.96 (2H, m, C-
H and C-6H), 7.49–7.69 (3H, m, ArH), 7.80–7.87 (2H, m, ArH
1718, 1610, 1385, 1259, 1173, 1085, and 777cm ; H-NMR
(400MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH CH ),
1.30–1.40 (6H, m, ─CH CH (CH CH ), 1.45–1.52 (2H, m,
─CH CH (CH ) CH ), 2.31 (3H, s, Ph-CH ), 2.36 (3H, s, C-4
─
a
b
3
)
2 5
3
2
2
2
)
2 3
3
8
2
2
2 3
3
3
1
3
and C-5H), 8.25 (1H, s, triazole H); C-NMR (100.6 MHz,
DMSO-d ): d 13.94 (─(CH CH ), 14.62 (C-4 CH ), 22.05
), 26.79 (─CH CH (CH CH ), 28.64
CH ), 31.00 (─(CH CH CH CH ), 52.54
CH ), 2.61 (2H, t, J = 8.1Hz ─CH (CH ) CH ), 3.77 (d,
3
2
2 4
3
6
)
2 5
3
3
1H, J =5.1 Hz, OH), 4.03–4.09 (2H, m, ─CH
(2H, m, ─CH and ─OCH
─OCH ), 5.16 (2H, s, ─CH
and ArH), 7.11–7.16 (1H, m, ArH), 7.47 (1H, d, J= 8.7 Hz, C-5H),
2
N), 4.53–4.58
(
(
(
1
(
(
1
5
─CH
─(CH
2
(CH
2
)
3
CH
(CH
2
CH
3
2
2
2
)
3
3
a
), 4.72 (1H, dd, J= 13.9 and 3.7 Hz,
2
OPh), 6.74–6.85 (5H, m, C-6H, C-8H,
2 2
) CH
2
)
2 2
3
)
2 3
2
2
3
b
─CH N), 61.76 (─CH), 67.61 (─OCH ), 70.06 (─OCH Ph),
2
2
2
13
01.01 (C-8), 109.06 (C-6), 112.18 (C-10), 113.87, 115.76, 122.17
3-ArC), 122.61 (C-3), 125.91 (C-5), 126.31 (CH═C), 130.66
ArC), 141.68 (CH═C), 146.64 (C-4), 148.69 (ArC), 153.02 (C-9),
58.55 (C-7), 160.37 (ArC), 160.90 (CO); HR-ESI-TOF-MS m/z
7.79 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl ): d 14.03
3
(─(CH
(CH CH
CH (CH
61.59 (─CH), 68.32 (─OCH ), 69.26 (─OCH Ph), 101.29 (C-8),
2
)
5
CH
CH
CH
3
), 14.78 (C-4 CH
), 27.47 (─CH
), 31.63 (─(CH
3
), 21.44 (Ph-CH
CH (CH CH ), 29.32 (─(CH
CH CH CH ), 53.01 (─CH N),
3 2
), 22.57 (─CH
2 3
)
2
3
2
2
2
)
3
3
2
)
2
2
2
)
2
3
2
)
3
2
2
3
2
+
+
37.2336 ([M + H] ), calcd for [C H N O +H] 537.2344.
28
32
4
7
2
2
3
-Hexyl-7-[2-hydroxy-3-(4-p-nitrophenoxymethyl-1,2,3-triazol-
111.44 (C-6), 112.11 (ArC), 114.75 (C-10), 115.48, 122.07
(2-ArC), 123.99 (C-3), 124.54 (C-5), 125.48 (CH═C), 129.18,
139.55 (2-ArC), 144.01 (CH═C), 146.04 (C-4), 153.29 (C-9),
158.06 (C-7), 159.91 (ArC), 162.07 (CO); HR-ESI-TOF-MS m/z
1
-yl)propyloxy]-4-methylcoumarin (16i).
white solid in 86% yield; mp 136–140 C; IR (KBr): 3367, 2929,
856, 1699, 1610, 1382, 1256, 1173, 1003, and 834 cm
H-NMR (400 MHz, DMSO-d ): d 0.84 (3H, t, J = 7.3 Hz,
It was obtained as
ꢀ
À1
2
;
1
+
+
506.2651 ([M + H] ), calcd for [C H N O + H] 506.2649.
6
28 35 3 5
─
(CH ) CH ), 1.26–1.33 (6H, m, ─CH CH (CH ) CH ),
3-Hexyl-7-[2-hydroxy-3-(4-p-tolyloxymethyl-1,2,3-triazol-1-yl)
2
5
3
2
2
2 3
3
1
.38–1.45 (2H, m, ─CH
CH ), 2.50–2.54 (2H, m, ─CH
m, ─CH N), 4.22–4.28 (1H, m, ─CH), 4.48 (1H, dd, J =13.9 and
2
CH
2
(CH
2
)
3
CH
3
), 2.37 (3H, s, C-4
propyloxy]-4-methylcoumarin (16l). It was obtained as white
ꢀ
3
2
(CH
)
2 4
CH
3
), 4.00–4.07 (2H,
solid in 84% yield; mp 130–134 C; IR (KBr): 3386, 2920, 2852,
À1
1
1721, 1610, 1383, 1247, 1176, 1089, and 831 cm ; H-NMR
2
7
.3 Hz, ─OCH ), 4.63 (1H, dd, J= 13.9 and 3.7 Hz, ─OCH ),
(400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH ) CH ),
a
b
3
2 5
3
5
.32 (2H, s, ─CH
2
OPh), 5.65 (1H, d, J= 5.1Hz, OH), 6.93–6.96
1.25–1.44 (6H, m, ─CH
2
CH
2
(CH
2
)
3
CH
3
), 1.45–1.54 (2H, m,
), 2.36 (3H, s, C-4
(CH2) CH ), 3.85 (1H,
(2H, m, C-8H and C-6H), 7.24–7.27 (2H, m, ArH), 7.67 (1H, d,
─CH
CH ), 2.61 (2H, t, J = 8.1 Hz, ─CH
2 2 2 3 3 3
CH (CH ) CH ), 2.27 (3H, s, Ph-CH
J= 8.8 Hz, C-5H), 8.18–8.22 (2H, m, ArH), 8.27 (1H, s, triazole
H); C-NMR (100.6 MHz, DMSO-d ): d 13.95 (─(CH ) CH ),
3
2
4
3
13
d, J = 5.1 Hz, OH), 4.03–4.10 (2H, m, ─CH N), 4.49–4.58
6
2 5
3
2
1
4.61 (C-4 CH3), 22.07 (─CH (CH ) CH CH ), 26.81
(2H, m, ─CH and ─OCH ), 4.72 (1H, dd, J= 13.9 and 3.7 Hz,
2
2 3
2
3
a
(
(
(
─CH
─(CH
─OCH
C-10), 115.20 (2-ArC), 122.62 (C-3), 125.83 (2-ArC), 126.05 (C-5),
2
CH
2
(CH
2
)
3
CH
3
), 28.66 (─(CH
), 52.58 (─CH
Ph), 101.02 (C-8), 112.28 (C-6), 113.88
2
)
2
CH
2
(CH
2
)
2
CH
3
), 31.10
─OCH
b 2
), 5.14 (2H, s, ─CH OPh), 6.75–6.86 (4H, m, C-8H, C-6H,
2
)
3
CH
2
CH
2
CH
3
2
N), 61.91 (─CH), 67.61
and ArH), 7.03–7.07 (2H, m, ArH), 7.47 (1H, d, J= 8.7 Hz, C-5H),
13
2
), 70.07 (─OCH
2
7.79 (1H, s, triazole H); C-NMR (100.6 MH
(─(CH ) CH ), 14.75 (C-4 CH ), 22.59 (Ph-CH ), 27.49 (─CH
2
Z 3
, CDCl ): d 14.05
(
2
5
3
3
3
126.32 (CH═C), 140.99 (ArC), 141.43 (CH═C), 146.65 (C-4),
(CH ) CH CH ), 29.34 (─CH CH (CH ) CH ), 53.34 (─(CH )
2 3 2 3 2 2 2 3 3 2
1
53.02 (C-9), 160.38 (C-7), 160.92 (ArC), 163.31 (CO); HR-ESI-
2
CH
62.12 (─CH), 68.36 (─OCH
105.24 (C-6), 112.04 (2-ArC), 114.77 (C-10), 121.83 (C-3), 124.52
2
(CH
2
)
2
CH
3
), 31.65 (─(CH
2
)
3
CH
2
CH
2
CH
3
), 53.00 (─CH
2
Ph), 101.27 (C-8),
2
N),
+
+
TOF-MS m/z 537.2341 ([M + H] ), calcd for [C28
H N O
32 4 7
+H]
2
), 69.25 (─OCH
537.2344.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Arya, V. Kumar, D. Mathur, S. Singh, R. Brahma, R. Singh, S. Singh, G. L. Sharma,
V. S. Parmar, and A. K. Prasad
Vol 000
(C-5), 125.70 (CH═C), 126.39, 127.42, 134.42 (3-ArC), 144.07
(100.6 MHz, CDCl3): d 14.06 (─(CH ) CH ), 14.82 (C-4
2 5 3
(
1
CH═C), 146.00 (C-4), 153.29 (C-9), 153.75 (ArC), 159.86 (C-7),
CH ), 22.59 (─CH (CH ) CH CH ), 27.49 (─CH CH (CH )
3
2
2 3
2
3
2
2
2
+
62.05 (CO); HR-ESI-TOF-MS m/z 506.2647 ([M + H] ), calcd for
3
CH
3
), 29.34 (─(CH
2
)
2
CH
2
(CH
2
)
2
CH
3
), 31.66 (─(CH
2
)
+
[C
29
H
35
N
3
O
5
+H] 506.2649.
3 2 2 3 2 2
CH CH CH ), 52.99 (─CH N), 61.88 (─CH), 68.37 (─OCH ),
3
-Hexyl-7-[2-hydroxy-3-(4-o-methoxyphenoxymethyl-1,2,3-
2
69.24 (─OCH Ph), 101.31 (ArC), 112.08 (C-8), 112.97 (C-6),
triazol-1-yl)propyloxy]-4-methylcoumarin (16m). It was obtained
114.83 (C-10), 115.24, 121.44 (2-ArC), 124.10 (C-3), 124.65
(C-5), 125.53 (CH═C), 130.26, 134.84 (2-ArC), 143.39 (CH═C),
146.01 (C-4), 153.31 (C-9), 158.75 (C-7), 159.85 (ArC), 162.06
ꢀ
as white solid in 83% yield; mp 86–90 C; IR (KBr): 3411, 2924,
À1
1
2
854, 1694, 1608, 1385, 1255, 1124, 1087, and 736 cm ; H-
NMR (400 MHz, CDCl ): d 0.89 (3H, t, J = 7.3 Hz, ─(CH
CH ), 1.25–1.40 (6H, m, ─CH CH (CH ) CH ), 1.45–1.52 (2H,
+
3
2
)
(CO); HR-ESI-TOF-MS m/z 618.1475 ([M + H] ), calcd for
+
[C H IN O + H] 1459.
5
3
2
2
2 3
3
28 32
3 5
m, ─CH CH (CH ) CH ), 2.37 (3H, s, C-4 CH ), 2.61 (2H, t,
3-Hexyl-7-[2-hydroxy-3-(4-p-iodophenoxymethyl-1,2,3-triazol-
2
2
2 3
3
3
J = 8.1 Hz, ─CH
2
(CH
2
)
4
CH
3
), 3.83 (4H, m, Ph-OCH
N), 4.45–4.55 (2H, m, ─CH and
3
and OH),
1-yl)propyloxy]-4-methylcoumarin (16p).
white solid in 85% yield; mp 158–163 C; IR (KBr): 3384, 2922,
2852, 1717, 1611, 1386, 1249, 1175, 1096, and 841 cm
It was obtained as
ꢀ
4
─
.01–4.05 (2H, m, ─CH
OCH ), 4.69 (1H, dd, J = 11.9 and 2.9 Hz, ─OCH
s, ─CH OPh), 6.76–7.04 (6H, m, C-8H, C-6H, and ArH), 7.47
2
À1
a
b
), 5.26 (2H,
;
1
H-NMR (400MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH )
2
3
2
13
(
1H, d, J = 8.8 Hz, C-5H), 7.83 (1H, s, triazole H); C-NMR
100.6MHz, CDCl ): d 14.05 (─(CH CH ), 14.80 (C-4 CH ),
CH CH ), 27.49 (─CH CH (CH CH ),
(CH CH ), 31.65 (─(CH CH CH CH ),
2.94 (─CH N), 55.75 (Ph-OCH3), 62.87 (─CH), 68.40
CH ), 1.26–1.42 (6H, m, ─CH CH (CH ) CH ), 1.46–1.54 (2H,
5 3 2 2 2 3 3
(
3
2
)
5
3
3
m, ─CH
J = 8.0Hz, ─CH
(2H, m, ─CH N), 4.53–4.59 (2H, m, ─CH and ─OCH
(1H, dd, J = 13.2 and 3.7 Hz, ─OCH ), 5.14 (2H, s, ─CH OPh),
2
CH
2
(CH
2
)
3
CH
3
), 2.37 (3H, s, C-4 CH
CH ), 3.77 (1H, brs, OH), 4.02–4.09
), 4.71
3
), 2.61 (2H, t,
2
2
5
2.59 (─CH
2
(CH
2
)
3
2
3
2
2
2
)
3
3
2
(CH
)
2 4
3
9.34 (─(CH
2
)
2
CH
2
2
)
2
3
2
)
3
2
2
3
2
a
2
b
2
(
─OCH ), 69.22 (─OCH Ph), 101.35 (C-8), 111.80 (C-6), 112.04
6.71–6.83 (4H, m, C-8H, C-6H, and ArH), 7.46–7.53 (3H,
2
2
13
(ArC), 114.31 (C-10), 114.80, 120.81, 121.89 (3-ArC), 124.08 (C-
m, ArH and C-5H), 7.80 (1H, s, triazole H); C-NMR
(100.6 MHz, CDCl ): d 14.05 (─(CH CH ), 14.83 (C-4 CH ),
22.58 (─CH (CH CH CH ), 27.48 (─CH CH (CH CH ), 29.33
(─(CH ) CH (CH ) CH ), 31.63 (─(CH ) CH CH CH ), 53.01
3
1
), 124.76 (C-5), 125.50 (CH═C), 144.08 (CH═C), 145.95 (C-4),
3
)
2 5
3
3
47.45, 149.52 (2-ArC), 153.33 (C-9), 159.89 (C-7), 162.02 (CO);
2
2
)
3
2
3
2
2
2
)
3
3
+
HR-ESI-TOF-MS m/z 522.2596 ([M + H] ), calcd for
2
2
2
2 2
3
2 3
2
2
3
+
[C H N O +H] 522.2599.
(─CH N), 61.69 (─CH), 68.29 (─OCH ), 69.26 (─OCH Ph),
29
35
3
6
2
2
2
3
-Hexyl-7-[2-hydroxy-3-(4-m-methoxyphenoxymethyl-1,2,3-
83.45 (ArC), 101.24 (C-8), 112.12 (C-6), 112.77 (C-10), 117.03
(2-ArC), 124.02 (C-3), 124.70 (C-5), 125.51 (CH═C), 138.19
(2-ArC), 143.39 (CH═C), 146.09 (C-4), 153.24 (C-9), 157.87
(ArC), 159.85 (C-7), 162.08 (CO); HR-ESI-TOF-MS m/z
618.1459 ([M + H] ), calcd for [C28H32IN O +H] 618.1459.
3 5
3-Hexyl-7-[2-hydroxy-3-(4-m-fluorophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (16q). It was obtained
triazol-1-yl)propyloxy]-4-methylcoumarin (16n). It was obtained
as white solid in 86% yield; mp 89–92 C; IR (KBr): 3222, 2923,
ꢀ
À1
1
2
853, 1715, 1609, 1301, 1201, 1160, 1051, and 783 cm ; H-
NMR (400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH
CH ), 1.25–1.42 (6H, m, ─CH CH (CH CH ), 1.46–1.54
2H, m, ─CH CH (CH CH ), 2.36 (3H, s, C-4 CH ), 2.61
2H, t, J=8.0Hz, ─CH (CH ) CH ), 3.76–3.79 ( 4H, m, OH
and Ph-OCH ), 4.03–4.10 (2H, m, ─CH N), 4.53–4.59 (2H, m,
CH and ─OCH
.16 (2H, s, ─CH
ArH), 6.76–6.85 (2H, m, ArH), 7.13–7.18 (1H, m, ArH), 7.48 (1H,
d, J= 8.8 Hz, C-5H), 7.80 (1H, s, triazole H);
+
+
3
2
)
5
3
2
2
2 3
)
3
(
(
2
2
)
2 3
3
3
ꢀ
as white solid in 87% yield; mp 120–122 C; IR (KBr): 3404, 2931,
2
2 4
3
À1
1
2858, 1702, 1615, 1335, 1287, 1158, 1087, and 844cm ; H-
NMR (400MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH
CH ), 1.23–1.40 (6H, m, ─CH CH (CH CH ), 1.45–1.52
(2H, m, ─CH CH (CH CH ), 2.36 (3H, s, C-4 CH ), 2.61 (2H,
t, J = 8.0 Hz, ─CH (CH ) CH ), 3.78 (1H, d, J = 5.12Hz, OH),
3
2
─
5
a
), 4.72 (1H, dd, J = 12.4 and 2.2 Hz, ─OCH
b
),
3
2
)
2
OPh), 6.51–6.57 (3H, m, C-8H, C-6H, and
5
3
2
2
)
2 3
3
2
2
)
2 3
3
3
13
C-NMR
2
2 4
3
(
100.6 MHz, CDCl ): d 14.03 (─(CH ) CH ), 14.78 (C-4 CH ),
4.00–4.07 (2H, m, ─CH N), 4.48–4.58 (2H, m, ─CH and
3
2 5
3
3
2
2
2
5
2.57 (─CH
9.32 (─(CH
2.98 (─CH
2
(CH
CH
N), 55.20 (Ph-OCH
2
)
3
CH
2
CH
3
), 27.47 (─CH
2
CH
2
(CH
2
)
3
CH
CH
3
),
),
─OCH
s, ─CH
7.23 (1H, m, ArH), 7.47 (1H, d, J = 8.8 Hz, C-5H), 7.82 (1H, s,
a
b
), 5.16 (2H,
2
)
2
2
(CH
2
2
) CH
3
), 31.64 (─(CH
2 3
) CH
2
CH
2
3
2
3
), 61.69 (─CH), 68.34
(─OCH ), 69.24 (─OCH Ph), 101.19 (ArC), 106.65 (C-8),
triazole H); C-NMR (100.6 MHz, CDCl ): d 14.05 (─(CH )
2
2
3 2
106.83, 112.08 (2-ArC), 114.77 (C-6), 124.02 (C-10), 124.59 (C-3),
CH ), 14.79 (C-4 CH ), 22.59 (─CH (CH ) CH CH ), 27.51
5 3 3 2 2 3 2 3
1
25.49 (C-5), 129.91 (CH═C), 143.81 (ArC), 146.03 (CH═C),
(─CH
(─(CH
(─OCH ), 69.23 (─OCH Ph), 101.34 (ArC), 102.46 (C-8),
2
CH
2
(CH
2
CH
2
)
3
CH
CH
3
3
), 29.35 (─(CH
2 2 2 2 2 3
) CH (CH ) CH ), 31.63
153.29 (C-4), 159.27 (C-9), 159.88 (C-7), 160.72 (2-ArC), 162.07
2
)
3
CH
2
), 52.97 (─CH N), 61.96 (─CH), 68.39
2
+
(CO); HR-ESI-TOF-MS m/z 522.2593 ([M + H] ), calcd for
2
2
+
[C H N O +H] 522.2599.
102.71, 107.99 (2-ArC), 108.21 (C-6), 110.29 (C-10), 112.06
(C-3), 114.87 (C-5), 124.14 (CH═C), 124.63 (ArC), 125.54
(CH═C), 130.33 (C-4), 143.49 (C-9), 145.99 (C-7), 153.33,
159.85 (2-ArC), 162.05 (CO); HR-ESI-TOF-MS m/z 510.2393
29 35 3 6
3
-Hexyl-7-[2-hydroxy-3-(4-o-iodophenoxymethyl-1,2,3-triazol-
1
-yl)propyloxy]-4-methylcoumarin (16o).
It was obtained as
ꢀ
white solid in 83% yield; mp 168–173 C; IR (KBr): 3285, 2924,
À1
+
+
2
855, 1717, 1618, 1333, 1297, 1169, 1086, and 761 cm
;
([M + H] ), calcd for [C H FN O + H] 510.2399.
28 32 3 5
1
H-NMR (400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH )
3-Hexyl-7-[2-hydroxy-3-(4-p-fluorophenoxymethyl-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (16r). It was obtained
3
2
5
CH
2H, m, ─CH
2H, t, J=8.0Hz, ─CH
.03–4.08 (2H, m, ─CH N), 4.54–4.63 (1H, m, ─CH and
3
), 1.25–1.42 (6H, m, ─CH
CH (CH CH
(CH
2
CH
2
(CH
2
)
3
CH
3
), 1.48–1.54
ꢀ
(
(
4
2
2
)
2 3
3
), 2.37 (3H, s, C-4 CH
CH ), 3.78 (1H, d, J= 5.2 Hz, OH),
3
), 2.61
as white solid in 85% yield; mp 126–129 C; IR (KBr): 3413, 2932,
À1
1
2
2
)
4
3
2859, 1702, 1615, 1355, 1216, 1158, 1087, and 829cm ; H-
NMR (400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH )
2
3
2
─
CH ), 1.30–1.42 (6H, m, ─CH CH (CH ) CH ), 1.46–1.54
a
b
5 3 2 2 2 3 3
(
2H, s, ─CH
(2H, m, ─CH
t, J=8.0Hz, ─CH
4.10 (2H, m, ─CH
2
CH
2
(CH
(CH
N), 4.50–4.60 (2H, m, ─CH and ─OCH
a
2
)
)
4
3
CH
CH ), 3.84 (1H, d, J= 4.4 Hz, OH), 4.03–
), 4.74
3 3
), 2.36 (3H, s, C-4 CH ), 2.61 (2H,
7
.25–7.30 (1H, m, ArH), 7.48 (1H, d, J = 8.8 Hz, C-5H),
2
2
3
7
.71–7.73 (1H, m, ArH), 7.89 (1H, s, triazole H); C-NMR
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
Synthesis of Potential Bioactive Novel 7-[2-Hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-
-alkyl-4-methylcoumarins
3
(
1H, dd, J= 13.2 and 2.9 Hz, ─OCH ), 5.14 (2H, s, ─CH OPh),
CH ), 1.23–1.40 (6H, m, ─CH CH (CH ) CH ), 1.45–1.52 (2H,
5 3 2 2 2 3 3
b
2
6
.75–6.97 (6H, m, C-8H, C-6H, and ArH), 7.47 (1H, d, J=8.8Hz,
m, ─CH CH (CH ) CH ), 2.33 (3H, s, C-4 CH ), 2.61 (2H, t,
2
2
2 3
3
3
13
C-5H), 7.81 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl
4.02 (─(CH CH ), 14.77 (C-4 CH ), 22.56 (─CH (CH
CH CH ), 27.45 (─CH CH (CH CH ), 29.31 (─(CH CH
CH ) CH ), 31.62 (─(CH ) CH CH CH ), 52.99 (─CH N), 62.26
3
): d
J = 8.0Hz, ─CH
(2H, m, ─CH
(1H, dd, J = 13.7 and 2.8 Hz, ─OCH
2
(CH
2
)
4
CH
3
), 3.89 (1H, brs, OH), 4.01–4.08
1
2
)
5
3
3
2
2
)
2
N), 4.52–4.59 (2H, m, ─CH and ─OCH
a
), 4.70
OPh),
3
2
3
2
2
2
)
3
3
2
)
2
2
b
), 5.36 (2H, s, ─CH
2
(
6.75–6.81 (2H, m, C-8H and C-6H), 6.91 (1H, d, J = 7.3 Hz,
ArH), 7.31–7.48 (5H, m, ArH), 7.76 (1H, d, J = 8.1Hz, C-5H),
2
2
3
2 3
2
2
3
2
(─CH), 68.29 (─OCH ), 69.25 (─OCH Ph), 101.23 (C-8), 112.12
2 2
1
3
(C-6), 114.75 (C-10), 115.69, 115.78, 115.92 (4-ArC), 123.99 (C-3),
7.86 (1H, s, triazole H); C-NMR (100.6 MHz, CDCl
(─(CH CH ), 14.82 (C-4 CH ), 22.59 (─CH (CH
27.51 (─CH CH (CH ) CH ), 29.34 (─(CH ) CH (CH ) CH ),
3
): d 14.05
124.64 (C-5), 125.49 (CH═C), 143.67 (CH═C), 146.09 (C-4),
)
2 5
3
3
2
2
)
3
CH CH ),
2
3
153.25 (C-9), 154.09, 156.21 (2-ArC), 159.87 (C-7), 162.09
2
2
2 3
3
2 2
2
2 2
3
+
(CO); HR-ESI-TOF-MS m/z 510.2399 ([M + H] ), calcd for
31.66 (─(CH ) CH CH CH ), 52.97 (─CH N), 63.40 (─CH),
2
3
2
2
3
2
+
[
C
H32FN O
28 3 5
+ H] 510.2399.
2 2
68.39 (─OCH ), 69.15 (─OCH Ph), 86.60 (C-8), 101.35
3
-Hexyl-7-[2-hydroxy-3-(4-(4-phenylphenoxymethyl)-1,2,3-
(ArC), 112.09 (C-6 and C-10), 112.73 (ArC and C-3), 114.85,
123.18 (2-ArC), 124.13 (C-5), 124.62 (3-ArC), 125.55 (CH═C),
129.55, 139.38 (2-ArC), 143.96 (CH═C), 145.97 (C-4), 153.34
(C-9), 156.59 (ArC), 159.86 (C-7), 162.03 (CO); HR-ESI-TOF-MS
triazol-1-yl)propyloxy]-4-methylcoumarin (16s). It was obtained
as white solid in 89% yield; mp 126–129 C; IR (KBr): 3421, 2925,
ꢀ
À1
1
2
(
1
─
856, 1707, 1609, 1387, 1251, 1085, and 761cm ; H-NMR
400MHz, CDCl ): d 0.88 (3H, t, J = 7.0 Hz, ─(CH CH ),
.26–1.44 (6H, m, ─CH CH (CH CH ), 1.46–1.54 (2H, m,
CH CH (CH CH ), 2.34 (3H, s, C-4 CH ), 2.61 (2H, t,
J = 8.1 Hz, ─CH (CH ) CH ), 3.79 (1H, brs, OH), 4.02–4.09
+
+
3
)
2 5
3
35 3 5
m/z 542.2652 ([M + H] ), calcd for [C32H N O +H] 542.2649.
2
2
)
2 3
3
2
2
)
2 3
3
3
2
2 4
3
CONCLUSIONS
(
2H, m, ─CH N), 4.51–4.57 (2H, m, ─CH and ─OCH ), 4.70
2
a
A practical and efficient synthesis of a series of two novel
7-(3-azido-2-hydroxypropyloxy)-3-alkyl-4-methylcoumarins
and 50 7-[2-hydroxy-3-(1,2,3-triazol-1-yl)propyloxy]-3-
alkyl-4-methylcoumarins has been reported in 80 to 92%
yields. The triazole-conjugated coumarins were synthesized
via Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction “click
chemistry.”
(
6
1H, dd, J = 13.7 and 2.8 Hz, ─OCH
.76–6.83 (2H, m, C-8H and C-6H), 7.01–7.04 (2H, m,
b
2
), 5.23 (2H, s, ─CH OPh),
ArH), 7.29–7.53 (8H, m, C-5H and ArH), 7.83 (1H, s, triazole H);
1
3
C-NMR (100.6MHz, CDCl ): d 14.03 (─(CH ) CH ), 14.74
3
2 5
3
(
C-4 CH ), 22.58 (─CH (CH ) CH CH ), 27.47 (─CH CH
3
2
2 3
2
3
2
2
(
2 3 3 2 2 2
CH ) CH ), 29.33 (─(CH ) CH (CH
2 2
)
CH
3
), 31.64 (─(CH
2
)
3
2 2 3 2
CH CH CH ), 53.02 (─CH N), 61.78 (─CH), 68.34 (─OCH
2
),
6
9.27 (─OCH Ph), 101.30 (C-8), 112.06 (C-6), 114.78 (C-10),
2
1
1
14.95, 124.02 (3-ArC), 124.02 (C-3), 124.64 (C-5), 125.49,
26.59 (3-ArC), 126.71 (CH═C), 128.08, 128.67, 134.22, 140.41
(
6-ArC), 143.85 (CH═C), 146.02 (C-4), 153.29 (C-9), 157.59
Acknowledgments. We are thankful to DRDO, New Delhi, and
University of Delhi for providing financial support under the
DU-DST Purse and the R&D Grant. A. A. thanks DBT, New
Delhi; V. K., D. M. and S. S. thank CSIR and UGC, New Delhi,
for providing junior and senior research fellowships.
(ArC), 159.88 (C-7), 162.06 (CO); HR-ESI-TOF-MS m/z
+
+
5
68.2804 ([M + H] ), calcd for [C H N O +H] 568.2806.
34 37 3 5
3
-Hexyl-7-[2-hydroxy-3-(4-(naphthalen-2-loxymethyl)-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (16t). It was obtained
as white solid in 89% yield; mp 139–140 C; IR (KBr): 3161, 2925,
ꢀ
À1
2
856, 1718, 1621, 1390, 1294, 1161, 1084, and 845cm
;
1
H-NMR (400 MHz, CDCl ): d 0.88 (3H, t, J = 7.3 Hz, ─(CH )
3
2
REFERENCES AND NOTES
CH ), 1.26–1.42 (6H, m, ─CH CH (CH ) CH ), 1.45–1.52
5
3
2
2
2 3
3
(
(
4
─
(
7
(
2H, m, ─CH
2H, t, J = 8.0Hz, ─CH
.02–4.09 (2H, m, ─CH
2
2
CH
2
(CH
2
)
3
CH
(CH
N), 4.48–4.58 (2H, m, ─CH and
OCH ), 4.70 (1H, dd, J = 13.7 and 2.8 Hz, ─OCH ), 5.29
3
), 2.34 (3H, s, C-4 CH
3
), 2.61
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2 4
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[
12.05 (C-6), 114.69 (C-10), 118.59 (ArC), 123.81 (C-3), 123.81,
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[
3
-Hexyl-7-[2-hydroxy-3-(4-(naphthalen-1-loxymethyl)-1,2,3-
triazol-1-yl)propyloxy]-4-methylcoumarin (16u). It was obtained
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[
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923, 2853, 1716, 1610, 1395, 1271, 1104, 1021, and 766cm
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