An efficient protocol for the synthesis of novel 1,2,3-triazole substituted 4H-chromene derivatives

Article abstract of DOI:10.1002/jhet.1850

A facile and an efficient protocol has been developed for the synthesis of novel 1,2,3-triazole substituted 4H-chromene derivatives 4 in single pot by multicomponent reaction of 1,3-cyclohexanedione, malononitrile and 1-substituted 1,2,3-triazole-5-aldehyde using potassium carbonate as catalyst.

Full text of DOI:10.1002/jhet.1850

Month 2014 An Efficient Protocol for the Synthesis of Novel 1,2,3-Triazole Substituted
4H-Chromene Derivatives
P. Sambasiva Rao, G. Malla Reddy, C. Kurumurthy, B. Veeraswamy, G. Santhosh Kumar,
*
P. Shanthan Rao, and B. Narsaiah
Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India
*
E-mail: narsaiahbanda84@gmail.com
Received June 18, 2012
DOI 10.1002/jhet.1850
Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com).
A facile and an efficient protocol has been developed for the synthesis of novel 1,2,3-triazole substituted
4H-chromene derivatives 4 in single pot by multicomponent reaction of 1,3-cyclohexanedione, malononitrile
and 1-substituted 1,2,3-triazole-5-aldehyde using potassium carbonate as catalyst.
J. Heterocyclic Chem., 00, 00 (2014).
INTRODUCTION
RESULTS AND DISCUSSION
Functionally substituted 4H-chromenes have received
considerable attention in the area of medicinal chemistry
because of their wide range of biological activity. Specifi-
cally, these derivatives are known to have antianalgesic [1],
antioxidant, spasmolytic, antibacterial [2], antianaphylactic,
anti-HIV [3], anticancer [4] and antiallergic activities [5].
The 4H-chromenes are also identified in the treatment
of neurodegenerative diseases, namely Alzheimer’s and
Parkinson’s diseases [6]. Alternatively, the 1,2,3-triazoles
because of their unique chemical and structural properties
received much attention over the past decade and found wide
applications in medicinal chemistry [7–11]. Recently,
multicomponent reactions are developed as efficient syn-
thetic tools that are overriding linear reactions because of
their significant advantages in terms of flexible reaction
conditions, series of reactions in single step, simplified
isolation procedures and thereby atom economy. Earlier
synthesis of chromene derivatives was adopted, such as three
component condensation of 1,3-diketones, aryl aldehydes
and malononitrile using piperidine [12,13], piperidine/
ammonium acetate [14], triethylamine [15], electrocatalysis
[16] and lipase [17]. On the basis of the importance
of chromene derivatives and 1,2,3-triazoles, our attention
was attracted toward the synthesis of novel 1,2,3-triazole
substituted 4H-chromene derivatives. In continuation of
our efforts [18–21] in developing new strategies for promis-
ing molecules, a new scaffold having both the moieties was
designed and we developed an efficient method for the
synthesis of novel 1,2,3-triazole substituted 4H-chromene
derivatives and reported it here for the first time.
Initially, phenyl substituted 1,2,3-triazole-4-aldehyde 1
[22], malononitrile 2 and cyclohexane-1,3-dione 3 were
selected as representative substrates and their reactions in
ethanol without catalyst at reflux temperature for 10 h were
investigated and found to give the corresponding chromene
in 46% yield. In order to improve the yield and to find
a suitable catalyst, the reaction was performed using
different catalysts such as ZnCl2, piperidine, tetrabutyl
ammonium bromide (TBAB), L-proline, K2CO3 and
CaCO3 and by neat grinding. Out of all the catalysts
studied, potassium carbonate was considered as the best
catalyst that gave product 4 in a high yield of 92%.
The reaction was outlined in Scheme 1. The investigation
on different catalysts and yields of products 4 formed at
different reaction temperatures versus times are tabulated
in Table 1.
After identifying potassium carbonate as suitable
catalyst for the reaction, the protocol was extended to
the multicomponent condensation of diverse substituted
1,2,3-triazol-4-aldehydes with 1,3-cyclohexanedione and
malononitrile and diverse substituted 4H-chromene
derivatives 4 were obtained. The sequence of reaction
is mainly a Knoevenagel condensation of malononitrile
with 1,2,3-triazol-4-aldehyde to form arylidene malononitrile
[23]. Michael addition of 1,3-cyclohexanedione with
in situ generated electron deficient Knoevenagel
adduct followed by intramolecular cyclization resulted
product 4. The details of the mechanism are outlined
in the next sections and the products are tabulated
in Table 2.
© 2014 HeteroCorporation

P. S. Rao, G. M. Reddy, C. Kurumurthy, B. Veeraswamy, G. Santhosh Kumar,
P. Shanthan Rao, and B. Narsaiah
Vol 000
Scheme 1
EXPERIMENTAL
Melting points were recorded in open glass capillaries on Casia-
Siamia (VMP-AM) Aldrich (Sigma-Aldrich, St. Louis, MO, USA)
and Spectrochem Pvt. Ltd (Mumbai, India) melting point apparatus
and are uncorrected. IR spectra were recorded on a Perkin-Elmer
FT-IR 240-C spectrophotometer using KBr optics. 1H NMR spectra
were recorded on a Bruker AV 300 MHz in CDCl3 and DMSO-d6
using TMS as internal standard. 13C NMR spectra were recorded
on Bruker AV 75 MHz (Germany) in CDCl3 and DMSO-d6.
Electron impact and chemical ionization mass spectra were
recorded on VG 7070 H instrument at 70eV. All the reactions were
monitored by thin-layer chromatography technique on precoated
silica gel 60 F254 (mesh) plates; spots were visualized with UV light.
Merck silica gel (60–120 mesh) was used for column chromato-
graphy. CHN analysis was recorded on a Vario EL analyzer.
Synthesis of 2-amino-5-oxo-4-(1-sustituted-1H-1,2,3-triazol-4-
yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile derivatives
(4a–p). General procedure. A mixture of 1-phenyl-1,2,3-triazol-
4-aldehyde 1 (200 mg, 1.08 mmol), malononitrile 2 (72 mg,
1.08 mmol) and K2CO3 (15 mg, 0.1 mmol) were taken in
ethanol (5 mL). The reaction mixture was heated to 50ꢀC and
kept for 4–5 min at the same temperature and white solid was
obtained. Then, 1,3-cyclohexanedione (120 mg, 1.08 mmol)
was added to the reaction mixture and refluxed for 5 min. As a
result, there is a change in color from red to colorless, which
indicates completion of reaction. After completion of reaction,
the reaction mixture was cooled to room temperature, and the
solvent was removed under vacuum. The crude product was
purified by letting it pass through a column packed with silica
gel using petroleum ether/EtOAc (6:4) as eluent.
2-Amino-5-oxo-4-(1-phenyl-1H-1,2,3-triazol-4-yl)-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4a). White solid, Yield:
92%, m.p. 208–210ꢀC, IR (KBr, cmÀ1): 3357, 3311 (─NH2), 2185
(─CN), 1687 (─C═O), 1653 (N═N); 1H NMR (DMSO-d6,
300 MHz): d 2.05 (m, 2H, ─CH2─), 2.39 (t, J=7.55Hz, 2H,
─CH2), 2.61 (t, J=7.58Hz, 2H, ─CH2), 4.61 (s, 1H, ─CH─),
6.61 (br, s, 2H, NH2), 7.43 (d, J = 7.89 Hz, 1H, Ar─H), 7.51
(t, J=7.89Hz, 2H, Ar─H), 7.80 (d, J=7.94Hz, 2H, Ar─H), 8.22
(s, 1H, Ar─H); 13C NMR (DMSO-d6, 75 MHz):191.4, 161.4,
154.2, 146.8, 145.8, 135.5, 132.7, 128.1, 126.7, 125.9, 116.6,
118.4, 115.8, 111.4, 36.4, 28.1, 26.4, 21.2; MS (ESI, 70 eV): m/z:
334 (M+ +H); Anal. Calcd for C18H15N5O2: C, 64.86; H, 4.54; N,
21.01; Found: C, 64.91; H, 4.51; N, 21.12%.
Table 1
Preparation of products 4.
Entry
Catalyst
Temp (ꢀC)
Time (h.min)
Yield (%)
a
1
2
3
4
5
6
7
8
9
78
78
78
78
78
60
100
78
10.00
12.00
3.00
3.30
2.30
0.10
0.30
0.30
0.30
46
52
66
65
82
92
70
75
56
—
a
ZnCl2
TBABa
L-Prolinea
Piperidinea
K2COa
b
K2CO3a
2-Amino-4-(1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
CaCO3
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4b).
White
c
—
27
solid, Yield: 89%, m.p. 202–203ꢀC, IR (KBr, cmÀ1): 3358,
3324 (─NH), 2181 (─CN), 1691 (─C═O), 1642 (N═N); 1H
NMR (DMSO-d6, 300 MHz): d 2.06 (m, 2H, ─CH2─), 2.36
(t, J = 7.54 Hz, 2H, ─CH2), 2.63 (t, J = 7.59 Hz, 2H, ─CH2),
4.58 (s, 1H, ─CH─), 6.66 (br, s, 2H, NH2), 7.30 (d,
J = 8.52 Hz, 2H, Ar─H), 7.85 (d, J = 8.52 Hz, 2H, Ar─H), 8.26
(s, 1H, Ar─H); MS (ESI, 70 eV): m/z: 352 (M+ + H); Anal.
Calcd for C18H14FN5O2: C, 61.53; H, 4.02; N, 19.93; Found:
C, 61.45; H, 4.05; N, 19.98%.
aReactions were carried out in ethanol.
bReactions were carried out in water.
cReactions were carried out by neat grinding.
CONCLUSION
A series of novel 1,2,3-triazole substituted 4H-chromene
derivatives were prepared in a single step by multicomponent
condensation of 1,3-cyclohexanedione, malononitrile and
diverse substituted 1,2,3-triazole-4-aldehydes using potas-
sium carbonate as an inexpensive catalyst. The developed
method is quite useful to the synthesis of diverse substituted
4H-chromene derivatives.
2-Amino-4-(1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4c).
White
solid, Yield: 88%, m.p. 190–192ꢀC, IR (KBr, cmÀ1): 3352,
3321 (─NH), 2183 (─CN), 1671 (─C═O), 1651 (N═N);
1H NMR (DMSO-d6, 300 MHz): d 2.08 (m, 2H, ─CH2─), 2.31
(t, J = 7.51Hz, 2H, ─CH2), 2.65 (t, J = 7.58Hz, 2H, ─CH2), 4.55
(s, 1H, ─CH─), 6.68 (br, s, 2H, NH2), 7.31 (d, J = 8.42 Hz, 2H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
An Efficient Protocol for the Synthesis of Novel 1,2,3-Triazole Substituted
4H-Chromene Derivatives
Table 2
Preparation of 1,2,3-triazole substituted 4H-chromene derivatives 4a–p.
S. No.
Compound
R
Time (min)
Yield (%)
m.p. (ꢀC)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
C6H5
4
4
4
5
5
10
10
10
10
10
10
10
10
10
10
10
92
89
88
85
85
81
84
84
80
81
80
82
76
72
80
71
208–210
202–203
190–192
188–189
184–186
205–206
211–213
185–186
216–218
206–208
209–210
218–219
166–167
182–184
188–189
192–194
4-FC6H4
4-ClC6H4
3-ClC6H4
4-BrC6H4
4-NO2C6H4
4-CH3C6H4
4-CH3OC6H4
4-CF3C6H4
2,4-F2C6H3
2,4-ClFC6H3
2,4-ClNO2C6H3
CH3─(CH2)6─CH2─
CF3─(CF2)5─(CH2)2─
CH3─(CH2)8─CH2─
CF3─(CF2)7─(CH2)2─
9
10
11
12
13
14
15
16
Ar─H), 7.81 (d, J = 8.42 Hz, 2H, Ar─H), 8.31 (s, 1H, Ar─H); MS
(ESI, 70eV): m/z: 368 (M+ + H); Anal. Calcd for C18H14ClN5O2: C,
58.78; H, 3.84; N, 19.04; Found: C, 58.71; H, 3.75; N, 19.16%.
2-Amino-4-(1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
2-Amino-5-oxo-4-(1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl)-
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4g). White
solid, Yield: 84%, m.p. 211–213ꢀC, IR (KBr, cmÀ1): 3354,
3313 (─NH), 2185 (─CN), 1687 (─C═O), 1643 (N═N);
1H NMR (DMSO-d6, 300 MHz): d 2.09 (m, 2H, ─CH2─), 2.21
(t, J = 7.65 Hz, 2H, ─CH2), 2.43 (s, 3H, ─CH3), 2.63
(t, J = 7.59 Hz, 2H, ─CH2), 4.64 (s, 1H, ─CH─), 6.61 (br, s,
2H, NH2), 7.44 (d, J = 7.84 Hz, 2H, Ar─H), 7.51 (d,
J = 7.84 Hz, 2H, Ar─H), 8.22 (s, 1H, Ar─H); MS (ESI, 70 eV):
m/z: 348 (M+ + H); Anal. Calcd for C19H17N5O2: C, 65.69; H,
4.93; N, 20.16; Found: C, 65.79; H, 4.99; N, 20.28%.
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4d).
White
solid, Yield: 85%, m.p. 188–189ꢀC, IR (KBr, cmÀ1): 3345,
3315 (─NH), 2189 (─CN), 1689 (─C═O), 1648 (N═N);
1H NMR (DMSO-d6, 300 MHz): d 2.08 (m, 2H, ─CH2─), 2.40
(t, J = 7.54 Hz, 2H, ─CH2), 2.64 (t, J = 7.65 Hz, 2H, ─CH2),
4.64 (s, 1H, ─CH─), 6.34 (br, s, 2H, NH2), 7.41 (d,
J = 7.41 Hz, 1H, Ar─H), 7.50 (dd, J = 7.41 Hz, J = 7.48 Hz, 1H,
Ar─H), 7.74 (d, J = 7.48 Hz, 1H, Ar─H), 7.85 (s, 1H, Ar─H),
8.21 (s, 1H, Ar─H); MS (ESI, 70 eV): m/z: 368 (M+ + H); Anal.
Calcd for C18H14ClN5O2: C, 58.78; H, 3.84; N, 19.04; Found:
C, 58.86; H, 3.83; N, 19.16%.
2-Amino-4-(1-(4-methoxyphenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4h).
White
solid, Yield: 84%, m.p. 185–186ꢀC, IR (KBr, cmÀ1): 3344, 3315
(─NH), 2177 (─CN), 1687 (─C═O), 1651 (N═N); 1H NMR
2-Amino-4-(1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
(DMSO-d6, 300MHz): d 2.05 (m, 2H, ─CH2─), 2.36
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4e).
White
(t, J = 7.55 Hz, 2H, ─CH2), 2.56 (t, J = 7.54 Hz, 2H, ─CH2), 3.62
(s, 3H, ─OCH3), 4.68 (s, 1H, ─CH─), 6.68 (br, s, 2H, NH2),
7.51 (d, J = 8.12 Hz, 2H, Ar─H), 7.80 (d, J =8.12 Hz, 2H,
Ar─H), 8.28 (s, 1H, Ar─H); MS (ESI, 70eV): m/z: 364
(M+ + H); Anal. Calcd for C19H17N5O3: C, 62.80; H, 4.72; N,
19.27; Found: C, 62.91; H, 4.75; N, 19.19%.
solid, Yield: 85%, m.p. 184–186ꢀC, IR (KBr, cmÀ1): 3342,
3323 (─NH), 2179 (─CN), 1693 (─C═O), 1649 (N═N);
1H NMR (DMSO-d6, 300 MHz): d 2.11 (m, 2H, ─CH2─), 2.31
(t, J = 7.67 Hz, 2H, ─CH2), 2.61 (t, J = 7.52 Hz, 2H, ─CH2),
4.54 (s, 1H, ─CH─), 6.56 (br, s, 2H, NH2), 7.38 (d,
J = 8.55 Hz, 1H, Ar─H), 7.80 (d, J = 8.55 Hz, 2H, Ar─H), 8.22
(s, 1H, Ar─H); MS (ESI, 70 eV): m/z: 412 (M+ + H); Anal.
Calcd for C18H14BrN5O2: C, 52.44; H, 3.42; N, 16.99; Found:
C, 52.36; H, 3.44; N, 16.88%.
2-Amino-5-oxo-4-(1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-
triazol-4-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(4i).
cmÀ1): 3349, 3321 (─NH), 2188 (─CN), 1681 (─C═O),
1612 (N═N); 1H NMR (DMSO-d6, 300 MHz):
2.11
White solid, Yield: 80%, m.p. 216–218ꢀC, IR (KBr,
2-Amino-4-(1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
d
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4f).
White
(m, 2H, ─CH2─), 2.32 (t, J = 7.62 Hz, 2H, ─CH2), 2.73
(t, J = 7.64 Hz, 2H, ─CH2), 4.73 (s, 1H, ─CH─), 6.81 (br,
s, 2H, NH2), 7.72 (d, J = 8.41 Hz, 2H, Ar─H), 7.88 (d,
J = 8.41 Hz, 2H, Ar─H), 8.31 (s, 1H, Ar─H); MS (ESI,
70 eV): m/z: 402 (M+ + H); Anal. Calcd for C19H14F3N5O2: C,
56.86; H, 3.52; N, 17.45; Found: C, 56.88; H, 3.41; N, 17.37%.
2-Amino-4-(1-(2,4-difluorophenyl)-1H-1,2,3-triazol-4-yl)-5-oxo-
5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (4j). White solid,
Yield: 81%, m.p. 206–208ꢀC, IR (KBr, cmÀ1): 3351, 3312 (─NH),
solid, Yield: 81%, m.p. 205–206ꢀC, IR (KBr, cmÀ1): 3359,
3317 (─NH), 2188 (─CN), 1687 (─C═O), 1645 (N═N); 1H
NMR (DMSO-d6, 300 MHz): d 2.08 (m, 2H, ─CH2─), 2.40
(t, J = 7.56 Hz, 2H, ─CH2), 2.64 (t, J = 7.61 Hz, 2H, ─CH2),
4.68 (s, 1H, ─CH─), 6.31 (br, s, 2H, NH2), 7.66 (d,
J = 8.92 Hz, 2H, Ar─H), 8.09 (d, J = 8.92 Hz, 2H, Ar─H),
8.41 (s, 1H, Ar─H); 13C NMR (DMSO-d6, 75 MHz):194.6,
163.4, 158.1, 149.3, 147.2, 136.6, 133.6, 129.7, 128.3, 126.9,
118.7, 118.4, 116.8, 111.4, 35.2, 26.1, 25.6, 18.5; MS (ESI,
70 eV): m/z: 379 (M+ + H); Anal. Calcd for C18H14N6O4: C,
57.14; H, 3.73; N, 22.21; Found: C, 57.19; H, 3.81; N, 22.29%.
1
2191 (─CN), 1698 (─C═O), 1651 (N═N); H NMR (DMSO-d6,
300 MHz): d 2.12 (m, 2H, ─CH2─), 2.38 (t, J=7.54Hz, 2H,
─CH2), 2.77 (t, J= 7.55 Hz, 2H, ─CH2), 4.89 (s, 1H, ─CH─),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

P. S. Rao, G. M. Reddy, C. Kurumurthy, B. Veeraswamy, G. Santhosh Kumar,
P. Shanthan Rao, and B. Narsaiah
Vol 000
6.74 (br, s, 2H, NH2), 7.72 (d, J= 8.34 Hz, 1H, Ar─H), 7.81
(d, J= 8.34 Hz, 1H, Ar─H), 7.94 (s, 1H, Ar─H), 8.38 (s, 1H,
Ar─H); MS (ESI, 70 eV): m/z: 370 (M+ +H); Anal. Calcd for
C18H13F2N5O2: C, 58.54; H, 3.55; N, 18.96; Found: C, 58.65; H,
3.53; N, 18.84%.
2-Amino-5-oxo-4-(1-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-
heptadecafluoro-decyl)-1H-1,2,3-triazol-4-yl)-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (4p). White solid, Yield: 71%, m.
p. 192–194ꢀC, IR (KBr, cmÀ1): 3351, 3319 (─NH), 2186
(─CN), 1689 (─C═O), 1633 (N═N); 1H NMR (DMSO-d6,
300 MHz): d 2.10 (m, 2H, ─CH2─), 2.41 (t, J = 7.68 Hz,
2H, ─CH2), 2.61 (m, 2H, ─CH2─), 2.66 (t, J = 7.63 Hz, 2H,
─CH2), 4.16 (t, J = 7.44 Hz, 2H, ─CH2), 4.51 (s, 1H,
─CH─), 6.76 (br, s, 2H, NH2), 8.29 (s, 1H, Ar─H); MS
(ESI, 70 eV): m/z: 704 (M+ + H); Anal. Calcd for
C22H14F17N5O2: C, 37.57; H, 2.01; N, 9.96; Found: C,
37.48; H, 2.12; N, 9.89%.
2-Amino-4-(1-(3-chloro-4-Fluorophenyl)-1H-1,2,3-triazol-
4-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(4k).
White solid, Yield: 80%, m.p. 209–210ꢀC, IR (KBr,
cmÀ1): 3351, 3319 (─NH), 2181 (─CN), 1689 (─C═O),
1
1641 (N═N); H NMR (DMSO-d6, 300 MHz): d 2.15 (m, 2H,
─CH2─), 2.43 (t, J = 7.55 Hz, 2H, ─CH2), 2.76 (t, J = 7.59Hz,
2H, ─CH2), 4.71 (s, 1H, ─CH─), 6.83 (br, s, 2H, NH2), 7.71
(d, J = 8.41 Hz, 1H, Ar─H), 7.79 (d, J = 8.41Hz, 1H, Ar─H),
7.88 (s, 1H, Ar─H), 8.41 (s, 1H, Ar─H); MS (ESI, 70 eV): m/z:
386 (M+ + H); Anal. Calcd for C18H13ClFN5O2: C, 56.04; H,
3.40; N, 18.15; Found: C, 56.19; H, 3.47; N, 18.27%.
2-Amino-4-(1-(2-chloro-4-nitrophenyl)-1H-1,2,3-triazol-
4-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile
(4l). White solid, Yield: 82%, m.p. 218–219ꢀC, IR (KBr,
cmÀ1): 3363, 3322 (─NH), 2198 (─CN), 1698 (─C═O),
1634 (N═N); 1H NMR (DMSO-d6, 300 MHz): d 2.15 (m,
2H, ─CH2─), 2.39 (t, J = 7.67 Hz, 2H, ─CH2), 2.69 (t,
J = 7.51 Hz, 2H, ─CH2), 4.81 (s, 1H, ─CH─), 6.82 (br, s,
2H, NH2), 7.91 (d, J = 8.43 Hz, 1H, Ar─H), 7.98 (d,
J = 8.43 Hz, 1H, Ar─H), 8.04 (s, 1H, Ar─H), 8.29 (s, 1H,
Ar─H); MS (ESI, 70 eV): m/z: 413 (M+ + H); Anal. Calcd
for C18H13ClN6O4: C, 52.37; H, 3.17; N, 20.36; Found: C,
52.48; H, 3.11; N, 20.24%.
Acknowledgments. Authors are thankful to Dr J. S. Yadav, Director,
IICT, for his constant encouragement and the authors (P. S. R.,
G. M. R., C. K., B. V., and G. S. K.) are thankful to the CSIR for
providing financial assistance in the form of Senior Research
Fellowship.
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2-Amino-5-oxo-4-(1-octyl-1H-1,2,3-triazol-4-yl)-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4m).
White solid,
Yield: 76%, m.p. 166–167ꢀC, IR (KBr, cmÀ1): 3347, 3328
(─NH), 2178 (─CN), 1699 (─C═O), 1653 (N═N); 1H NMR
(DMSO-d6, 300 MHz): d 0.91 (t, J = 6.58 Hz, 3H, ─CH3), 1.29
(m, 10H, ─CH2), 1.87 (m, 2H, ─CH2─), 2.11 (m, 2H, ─CH2─),
2.41 (t, J = 6.93 Hz, 2H, ─CH2), 2.56 (t, J = 7.11Hz, 2H, ─CH2),
4.11 (t, J = 6.68 Hz, 2H, ─CH2), 4.76 (s, 1H, ─CH─), 6.61 (br, s,
2H, NH2), 8.32 (s, 1H, Ar─H); MS (ESI, 70eV): m/z: 370
(M+ + H); Anal. Calcd for C20H27N5O2: C, 65.02; H, 7.37; N,
18.96; Found: C, 65.11; H, 7.38; N, 18.88%.
2-Amino-5-oxo-4-(1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-
octyl)-1H-1,2,3-triazol-4-yl)-5,6,7,8-tetrahydro-4H-chromene-
3-carbonitrile (4n). White solid, Yield: 80%, m.p. 182–184ꢀC,
IR (KBr, cmÀ1): 3356, 3313 (─NH), 2175 (─CN), 1681
1
(─C═O), 1637 (N═N); H NMR (DMSO-d6, 300MHz): d 2.08
(m, 2H, ─CH2─), 2.39 (t, J = 6.67 Hz, 2H, ─CH2), 2.61 (m, 2H,
─CH2─), 2.68 (t, J = 7.27Hz, 2H, ─CH2), 4.11 (t, J = 7.67Hz,
2H, ─CH2), 4.61 (s, 1H, ─CH─), 6.66 (br, s, 2H, NH2), 8.21
(s, 1H, Ar─H); MS (ESI, 70eV): m/z: 604 (M+ + H); Anal. Calcd
for C20H14F13N5O2: C, 39.81; H, 2.34; N, 11.61; Found: C,
39.73; H, 2.34; N, 11.69%.
2-Amino-5-oxo-4-(1-decyl-1H-1,2,3-triazol-4-yl)-5,6,7,8-
tetrahydro-4H-chromene-3-carbonitrile (4o).
White solid,
Yield: 72%, m.p. 188–189ꢀC, IR (KBr, cmÀ1): 3344, 3321
(─NH), 2195 (─CN), 1697 (─C═O), 1643 (N═N);
1H NMR (DMSO-d6, 300 MHz): d 0.96 (t, J = 6.52 Hz, 3H,
─CH3), 1.28 (m, 14H, ─CH2), 1.88 (m, 2H, ─CH2), 2.15
(m, 2H, ─CH2─), 2.44 (t, J = 7.23 Hz, 2H, ─CH2), 2.58 (t,
J = 7.61 Hz, 2H, ─CH2─), 4.17 (t, J = 7.68 Hz, 2H, ─CH2),
4.76 (s, 1H, ─CH─), 6.71 (br, s, 2H, NH2), 8.28 (s, 1H,
Ar─H); MS (ESI, 70 eV): m/z: 398 (M+ + H); Anal. Calcd
for C22H31N5O2: C, 66.47; H, 7.86; N, 17.62; Found: C,
66.39; H, 7.77; N, 17.74%.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2014
An Efficient Protocol for the Synthesis of Novel 1,2,3-Triazole Substituted
4H-Chromene Derivatives
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet