Catalytic synthesis of coumarin-linked nicotinonitrile derivatives via a cooperative vinylogous anomeric-based oxidation

Article abstract of DOI:10.1007/s11164-020-04267-9

Abstract: In the presented study, we developed a new and efficient strategy for the synthesis of coumarin-linked nicotinonitrile derivatives via a cooperative vinylogous anomeric-based oxidation mechanism. Target compounds were prepared through a four com

Full text of DOI:10.1007/s11164-020-04267-9

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04267-9
Catalytic synthesis of coumarin‑linked nicotinonitrile
derivatives via a cooperative vinylogous anomeric‑based
oxidation
Morteza Torabi1 · Meysam Yarie1 · Fatemeh Karimi1 · Mohammad Ali Zolfgol1
Received: 18 May 2020 / Accepted: 3 September 2020
© Springer Nature B.V. 2020
Abstract
In the presented study, we developed a new and efcient strategy for the synthesis of
coumarin-linked nicotinonitrile derivatives via a cooperative vinylogous anomeric-
based oxidation mechanism. Target compounds were prepared through a four com-
ponent reaction between aldehyde derivatives, 2-acetyl-3H-benzo[f]chromen-3-one
or 3-acetylcoumarin, malononitrile or ethyl cyanoacetate and ammonium acetate, in
the presence a catalytic amount of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole with
sulfonic acid tags as a recoverable nanomagnetic catalyst. All reactions proceed
smoothly with good to high yields under solvent free conditions.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04267-9) contains supplementary material, which is available to authorized users.
*
Mohammad Ali Zolfgol
mzolfgol@yahoo.com
1
Department of Organic Chemistry, Faculty of Chemistry, Bu‐Ali Sina University,
6517838683 Hamedan, Iran
Vol.:(0123456789)
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M. Torabi et al.
Graphic abstract
Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole with sulfonic acid tags shows elegant
catalytic activity for the preparation of coumarin linked nicotinonitrile derivateives
via a cooperative vinylogous anomeric based oxidation mechanism.
Keywords Coumarin-linked nicotinonitrile · Cooperative vinylogous anomeric-
based oxidation · Multi-component reaction · Nanomagnetic catalyst
Introduction
Over the last decade, much efort has been made to achieve the concept of "ideal syn-
thesis" by chemists. Through ideal synthesis, the target molecule, prepared via a single
step and one pot manner by applying readily available starting materials without any
side-product formation (100% yield). Ideal synthesis is an environmentally friendly,
resource efective, simple, safe and economically acceptable protocol [1, 2]. In terms of
concept, one of the closest methods to "ideal synthesis" is multi-component reactions
(MCRs) strategy, which covers several aspects of it [3]. MCRs, as an important class of
Scheme 1 Hidden ionicity in
N-(chloromethyl)piperidine due
to anomeric efect
1 3

Catalytic synthesis of coumarin-linked nicotinonitrile…
Scheme 2 Vinylogous anomeric
efect operates in the exocyclic
π-systems
chemical transformations, incorporate three or more starting materials for the synthesis
of complex molecule through a low synthetic cost and high atom economy procedure
[4]. The concept of MCRs is well reviewed [5–12].
Construction of catalytic systems which displays high activity and selectivity (such
as homogeneous catalysts) and possesses the easy separation and reusability (such as
heterogeneous catalysts) has become a hot research topic in the domain of modern
organic synthesis [13]. By applying magnetic nanoparticles in the preparation of cata-
lytic systems, both of the superior characteristics of homogeneous and heterogeneous
catalysts can be simultaneously achieved. Catalytic systems are based on magnetic
Scheme 3 Catalytic synthesis of coumarin-linked nicotinonitrile derivatives in the presence a catalytic
amount of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic acid
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M. Torabi et al.
nanoparticles holding various admirable features including high surface area to bulk
ratios, easy surface modifcation, high activity, selectivity, thermal and chemical stabil-
ity. By these characteristic technics, applying heterogeneous magnetic nanoparticles as
catalysts can bring chemists closer to "ideal synthesis" [14–20].
Due to the diverse capabilities of pyridine systems in diferent chemical domains
of applications including natural products, bioactive compounds and market drugs,
agrochemicals, material science and catalysis, researchers’ interest in these versatile
molecules have been extensively intensifed [21–25]. On the other hands, coumarin-
containing heterocyclic molecules are widespread in natural products and represent
varied pharmacological usages such as anti-infammatory, antioxidant, antitumor and
antimicrobial activities. One the shining example of commercially available drugs
bearing coumarin moiety is Novobiocin which applied as antimicrobial agent [26–30].
Therefore, it can be expected that the existence of two biological active sites within the
structure of a single molecule gives unique pharmaceutical features to that molecule.
Despite the unique characteristics of coumarin-linked pyridine systems, a few methods
have been reported for their synthesis [31–41]. Therefore, presenting a powerful and
efcient method for their preparation is highly desirable.
After the discovery of the concept of anomeric efect, it is widely applied for expla-
nation of several unusual phenomena [42–60]. For example, the hidden ionicity of
N-(chloromethyl)piperidine can be explained by the anomeric interactions between
nitrogen lone pairs with C–Cl anti-bonding orbital (nN→σ*C–Cl). In this compound,
due to salt-like reactivity, the chlorine atom is quantitatively precipitated by AgNO3
and can be exchanged to a perchlorate anion (Scheme 1) [61].
In vinylogous anomeric efect, the anomeric interactions are transmitted through
double bonds. For example, vinylogous anomeric efect can operate with exocyclic
π-systems such as alkenes and ketoximes (Scheme 2) [44, 62–71].
In this paper, in order to expand the concepts of anomeric-based oxidation and coop-
erative vinylogous anomeric-based oxidation [72, 73], and reported new protocols for
the synthesis of pyridine derivatives [74–78], we investigated the catalytic performance
of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic acid at the synthesis of cou-
marin-linked nicotinonitrile derivatives under gentle reaction conditions (Scheme 3).
Results and discussion
Cooperativity of stereoelectronic efects has been observed when more than one
donor working together. We have recently introduced "cooperative vinylogous ano-
meric-based oxidations" based on the use of the vinylogous anomeric efect for the
removal of hydride, a major stage which is needed to support the fnal oxidation/
aromatization in the synthesis of susceptible molecules [73]. Since that the devel-
opment of anomeric-based oxidation (ABO) is our main interest [72], herein the
multi-component synthesis of coumarin-linked nicotinonitrile derivatives, which are
able to take advantage of the cooperative vinylogous anomeric interactions between
nitrogen lone pairs (nN) and the allylic σ*C–H orbital (nN →σ*C–H) and aromatization
of the N-hetero cycle ring under acidic conditions, is reported.
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Catalytic synthesis of coumarin-linked nicotinonitrile…
Table 1 Surveying of the diferent catalysts upon the synthetic reaction of target molecule 1aa
O
N
O
O
Solvent-free, 80°C, 20 min.
H
NH4OAc
N
N
N
NH2
O
O
O
1a
Entry
Utilized catalyst
Load of catalyst
Yield (%)b
1
2
3
4
5
Silica sulfuric acid (SSA)
Fe3O4
Fe3O4@SiO2
10 mg
10 mg
10 mg
10 mg
10 mg
82
42
40
63
80
Fe3O4@SiO2@(CH2)3-urea-benzimidazole
Fe3O4@SiO2@(CH2)3-urea-benzimidazole sul-
fonic acid
6
7
8
9
10
11
13
14
15
16
17
18
FeCl3
AlCl3
H2SO4
HCl
NH2SO3H
Al(HSO4)3
Fe(HSO4)3
Ca(HSO4)2
CAN
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
10 mol%
38
36
62
88
58
42
48
46
78
36
72
85
NaHCO3
Oxalic acid
p-Toluenesulfonic acid (PTSA)
aReaction condition: benzaldehyde (1 mmol, 0.106 g), malononitrile (1 mmol, 0.066 g), 2-acetyl-3H-
benzo[f]chromen-3-one (1 mmol, 0.238 g) and ammonium acetate (1 mmol, 0.077 g), solvent free, 80 °C,
20 min
bIsolated yields
Application of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic acid
in the synthesis of coumarin‑linked nicotinonitrile derivatives
At frst, to fnd the best catalyst for the synthesis of coumarin-linked nicotinoni-
trile derivatives, several catalysts were explored upon the reaction of benzaldehyde,
2-acetyl-3H-benzo[f]chromen-3-one, malononirtile and ammonium acetate as a
model reaction under solvent-free conditions at 80 °C at 20 min and the achieved
data are embedded in Table 1.
From the obtained experimental data as inserted in Table 1, it can be inferred that
in addition to the Fe3O4@SiO2@(CH2)3-urea-benzimidazole sulfonic acid (entry 5),
the model reaction performed well in the presence of SSA (entry 1), HCl (entry 9)
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M. Torabi et al.
Table 2 Optimizing of the reaction condition for the synthesis of coumarin-linked nicotinonitrile 1aa
O
N
O
O
Optimal reaction conditions ?
H
NH4OAc
O
N
N
N
NH2
O
O
O
O
N
1a
Fe3O4
SiO2
O
O
Si
N
H
N
H
N
S
O
O
OH
Fe3O4@SiO2@(CH2)3-urea-benzimidazole sulfonic acid
Entry
Solvent
Temperature (°C) Load of catalyst (mg)
Time (min.)
Yield (%)b
1
–
–
–
90
80
80
80
80
80
70
60
10
20
10
5
–
–
10
10
10
10
10
10
10
10
10
10
15
20
20
30
20
120
20
35
20
120
120
120
240
120
240
240
78
82
80
67
35
60
70
62
Trace
30
-
2
3c
4
5
6
7
8
–
–
–
–
–
–
9
r.t.
r.t.
10
11
12
13
14
15
16
H2O
EtOH
n-Hexane
EtOAc
CH2Cl2
PEG
Refux
Refux
Refux
Refux
Refux
120
65
61
78
–
83
aReaction condition: benzaldehyde (1 mmol, 0.106 g), malononitrile (1 mmol, 0.066 g), 2-acetyl-3H-
benzo[f]chromen-3-one (1 mmol, 0.238 g) and ammonium acetate (1 mmol, 0.077 g), bIsolated yields,
cData for the model reaction under air, nitrogen and argon atmosphere are similar
and PTSA (entry 18) and shows comparative results. But from the recovering and
reusing viewpoint, the Fe3O4@SiO2@(CH2)3-urea-benzimidazole sulfonic acid is
the best choice.
In the next step, for evaluation the optimal operational reaction conditions, we
tested the model reaction in the presence of diferent amounts of Fe3O4@SiO2@
(CH2)3-urea-benzimidazole sulfonic acid, varied solvents and also solvent free con-
ditions under various operational temperatures. Afterward, by collecting and investi-
gating the resulting data as summarized in Table 2, we found that solvent-free condi-
tions, 80 °C and using 10 mg of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic
acid, provide the best results for the model reaction (Table 2, Entry 3).
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Catalytic synthesis of coumarin-linked nicotinonitrile…
Table 3 Catalytic synthesis of coumarin-linked nicotinonitrile derivatives under mild reaction
conditionsa
aReaction condition: aryl aldehyde (1 mmol), malononitrile or ethyl cyanoacetate (1 mmol), 2-acetyl-3H-
benzo[f]chromen-3-one or 3-acetylcoumarin (1 mmol) and ammonium acetate (1 mmol, 0.077 g), solvent
free, 80 °C, catalyst=10 mg, reported yields are referred to isolated yields
In the next step, in another set of reactions, by the optimal reaction parameters
in hands, this multi-component reaction pathway, applied for the synthesis of cou-
marin-linked nicotinonitriles. In this step, the scope and generality of the reaction
expanded by applying diferent arylaldehydes, 2-acetyl-3H-benzo[f]chromen-3-one
or 3-acetylcoumarin, malononitrile or ethyl cyanoacetate and ammonium acetate.
The obtained data as inserted in Table 3 show that the presented protocol is a power-
ful and efcient method for the synthesis of varied coumarin-linked nicotinonitrile
derivatives.
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M. Torabi et al.
Fig. 1 The reusing test of the
described nanomagnetic catalyst
Scheme 4 Plausible mechanistic process for the synthesis of target molecule 1a via a cooperative vinylo-
gous anomeric-based oxidation
Recovery and reusing test
The reusability is one of the valuable advantages of any catalytic systems. In
a separate study, the recyclability of Fe3O4@SiO2@(CH2)3‐urea‐benzimida-
zole sulfonic acid was also investigated upon the condensation reaction between
1 3

Catalytic synthesis of coumarin-linked nicotinonitrile…
benzaldehyde, malononitrile, 2-acetyl-3H-benzo[f]chromen-3-one and ammo-
nium acetate in 20 min. After completion of each run, hot CHCl3 was added
to the reaction mixture. The desired product and unreacted starting materials
dissolve in hot CHCl3, but the nanomagnetic catalyst is not soluble. Afterward,
using an external magnet, the nanomagnetic catalyst was separated from the
reaction mixture and thoroughly washed with CHCl3 and preserved for the next
run. The reuse test was successful over fve continuous runs with only a mar-
ginal decreasing in its catalytic activity (Fig. 1).
In a suggested plausible reaction mechanism as portrayed in the Scheme 4,
in the presence of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic acid, the
enamine intermediate A (generated from the reaction of ammonium acetate and
related methylketone), attacked as a nucleophile to Knoevenagel intermediate
B which is converted to the intermediate C. In the next step, through intramo-
lecular nucleophilic attack, intermediate C converted to intermediate D. In the
last step, via a cooperative vinylogous anomeric-based oxidation (nN → σ*C–H
(CVABO) pathway, target molecule 1a is produced.
)
Conclusions
In summary, the catalytic application of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole
sulfonic acid as a recoverable nanomagnetic catalyst was investigated in the con-
struction of coumarin-linked nicotinonitrile derivatives through a four component
reaction between aldehyde derivatives, 2-acetyl-3H-benzo[f]chromen-3-one or
3-acetylcoumarin, malononitrile or ethyl cyanoacetate and ammonium acetate under
mild and solvent‐free reaction conditions with good to high yields. The fnal step
of the mechanistic route for the synthesis of target molecules has proceeded via a
cooperative vinylogous anomeric-based oxidation mechanism. In an extension of the
classic anomeric efect, this research presented vinyl heteroatoms are able to donate
electron density from their lone pairs into the accepting σ* orbital through an inter-
vening π orbitals. Also, the applied nanomagnetic catalyst has excellent reusability
in the investigated multi-component reactions.
Experimental
The commercially available chemicals were obtained from Sigma-Aldrich and
Merck chemical companies and used as received without further purifcation. The
reaction progress and purity of the prepared structures were monitored by TLC
performed with silica gel SIL G/UV 254 plates. FT-IR spectra were recorded
1
on a PerkinElmer Spectrum Version 10.02.00 using KBr pellets. The H NMR
(300 MHz) and 13C NMR (75 MHz) spectra were recorded on a Bruker spectrom-
eter (δ in ppm) using DMSO-d6 as solvent with chemical shifts measured relative
to Si(CH3)4 as internal standard. Melting points were determined with a Buchi
B‐545 melting point apparatus in open capillary tubes.
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M. Torabi et al.
General procedure for construction of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole
sulfonic acid
The reusable biological urea-based nanomagnetic catalyst namely Fe3O4@SiO2@
(CH2)3‐urea‐benzimidazole sulfonic acid was prepared based on our recently reported
protocol [76].
General procedure for the synthesis of 2‑acetyl‑3H‑benzo[f]chromen‑3‑one
In a round bottom fask, a mixture of 2-hydroxy-1-naphtaldehyde (20 mmol, 3.4 g) and
ethyl acetoacetate (20 mmol, 2.6 g) and dimethylamine (0.5 mL) in 10 mL EtOH was
stirred at 60 °C for 12 h. After that, the yellow precipitate fltered of and washed with
ethanol to obtain pure product.
General procedure for the synthesis of 3‑acetylcoumarin
According to the previously reported procedures [35, 38–41, 75], a mixture of
2-hydroxy benzaldehyde (20 mmol, 2.4 g), ethyl acetoacetate (20 mmol, 2.6 g) and
dimethylamine (0.5 mL) in 10 mL distilled water was stirred at room temperature until
a yellow precipitate was formed. After that, the precipitate fltered of, washed several
times with ethanol to give pure 3-acetylcoumarin.
General procedure for the synthesis of coumarin‑linked nicotinonitrile
derivatives
To a mixture of aromatic aldehydes (1 mmol), 2-acetyl-3H-benzo[f]chromen-3-one
(1 mmol, 0.238 g) or 3-acetylcoumarin (1 mmol, 0.188 g), malononitrile (1 mmol,
0.066 g) or ethyl cyanoacetate (1 mmol, 0.113 g) and ammonium acetate (1.5 mmol,
0.116 g), 10 mg of Fe3O4@SiO2@(CH2)3‐urea‐benzimidazole sulfonic acid were
added as a catalyst. The obtained reaction mixture was stirred under solvent‐free condi-
tions at 80 °C according to the appropriate times (Table 3). The reaction progress was
monitored by TLC using n‐hexane: EtOAc (1:1) as eluent. After the reaction was com-
pleted, in order to separate the catalyst, hot CHCl3 was added to the reaction mixture
and the desired products and unreacted starting materials were dissolved. Afterward,
undissolved nanomagnetic catalyst was easily separated from the reaction mixture by
utilizing an external magnet, washed with CHCl3 and recovered for subsequent reac-
tion. After evaporation of solvent, the crude solid was obtained by adding methanol
and fnally was purifed using CH2Cl2. The desired products were obtained in good to
excellent isolated yields as presented in Table 3.
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Catalytic synthesis of coumarin-linked nicotinonitrile…
Selected spectral data
2‑Acetyl‑3H‑benzo[f]chromen‑3‑one
M.p.=184–186 °C, FT‐IR (KBr, ν, cm−1): 3065, 2932, 1734, 1674, 1557, 1221,
1207.
1H NMR (301 MHz, DMSO-d6) δppm: 9.28(s, 1H, Chromene ring), 8.63 (d, 1H,
J=9 Hz, Aromatic), 8.34 (d, 1H, J=9 Hz, Aromatic), 8.10 (d, 1H, J=9 Hz, Aro-
matic), 7.83–7.77(m, 1H, Aromatic), 7.71–7.65 (m, 1H, Aromatic), 7.64 (d, 1H,
J=9 Hz, Aromatic), 2.67 (S, 3H, Me).
13C NMR (76 MHz, DMSO-d6) δppm: 195.6, 158.9, 155.8, 142.9, 136.7, 130.4,
129.9, 129.6, 127.0, 123.6, 122.8, 116.9, 112.8.
2‑Amino‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)‑4‑phenylnicotinonitrile (1a)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3498, 3376, 2213, 1727, 1623, 1568, 1214.
1H NMR (301 MHz, DMSO-d6) δppm: 9.72 (s, 1H, Chromene ring), 8.57 (d, 1H,
J=6 Hz, Aromatic), 8.31 (d, 1H, J=6 Hz, Aromatic), 8.13 (d, 1H, J=6 Hz, Aro-
matic), 7.85–7.80 (m, 2H, Aromatic), 7.66–7.61 (m, 7H, Aromatic and Pyridine
ring), 7.17 (br, 2H, NH2).
13C NMR (76 MHz, DMSO-d6) δppm: 160.7, 159.5, 155.4, 154.3, 153.7, 140.0,
137.5, 135.2, 130.5, 130.2, 129.7, 129.5, 129.4, 129.3, 129.1, 128.6, 126.9, 122.6,
122.3, 117.2, 116.9, 113.5, 112.8, 88.6.
MS (EI, 70 eV), m/z (%): 389.
2‑Amino‑4‑(4‑chlorophenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1b)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3490, 3350, 3056, 2208, 1724, 1609, 1567,
1209.
1H NMR (301 MHz, DMSO-d6) δppm: 9.72 (s, 1H, Chromene ring), 8.56 (br, 1H,
Aromatic), 8.31 (br, 1H, Aromatic), 8.14 (br, 1H, Aromatic), 7.86–7.68 (m, 8H,
Aromatic and Pyridine ring), 7.25 (br, 2H, NH2).
13C NMR (76 MHz, DMSO-d6) δppm: 160.6, 159.5, 154.3, 154.0, 153.8, 140.0,
136.2, 135.2, 135.1, 130.5, 130.5, 129.7, 129.5, 129.2, 126.9, 122.4, 122.3, 119.0,
117.0, 116.9, 113.4, 112.5, 88.4.
MS (EI, 70 eV), m/z (%): 423.
2‑Amino‑4‑(2,4‑dichlorophenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)
nicotinonitrile (1c)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3473, 3354, 3061, 2210, 1722, 1628, 1570,
1553, 1517, 1277.
1H NMR (301 MHz, DMSO-d6) δppm: 9.72 (s, 1H, Chromene ring), 8.55 (d,
1H, J=9 Hz, Aromatic), 8.30 (d, 1H, J=9 Hz, Aromatic), 8.12 (d, 1H, J= 9 Hz,
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M. Torabi et al.
Aromatic), 7.89 (br, 1H, Aromatic), 7.89 (br, 1H, Aromatic), 7.71–7.56 (m, 5H,
Aromatic and Pyridine ring), 7.30 (br, 2H, NH2).
13C NMR (76 MHz, DMSO-d6) δppm: 160.0, 159.4, 154.4, 153.8, 152.4, 140.2,
135.5, 135.4, 135.3, 132.9, 132.3, 130.5, 129.9, 129.7, 129.5, 129.3, 128.4, 126.89,
122.3, 122.2, 116.9, 116.2, 113.5, 112.9, 90.2.
MS (EI, 70 eV), m/z (%): 458.
2‑Amino‑4‑(4‑bromophenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1d)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3486, 3387, 3064, 2926, 2212, 1728, 1626,
1564, 1218, 819.
1H NMR (301 MHz, DMSO-d6) δppm: 9.68 (s, 1H, Chromene ring), 8.53 (d, 1H,
J=9 Hz, Aromatic), 8.28 (d, 1H, J=6 Hz, Aromatic), 8.10 (d, 1H, J=6 Hz, Aro-
matic), 7.82–7.79 (m, 2H, Aromatic), 7.76 (s, 1H, Pyridine ring), 7.70–7.63 (m, 3H,
Aromatic), 77.59 (d, 2H, J = 9 Hz, Aromatic), 7.20 (br, 2H, NH2).
13C NMR (76 MHz, DMSO-d6) δppm: 158.9, 154.1, 153.9, 149.1, 144.6, 141.1,
137.0, 135.0, 132.4, 132.3, 131.2, 130.8, 130.5, 129.5, 129.1, 126.9, 124.4, 123.7,
123.1, 119.9, 117.0, 116.2, 113.4, 112.5, 96.4, 95.4, 79.9.
MS (EI, 70 eV), m/z (%): 468.
2‑Amino‑4‑(4‑hydroxyphenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1e)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3496, 3380, 2955, 2210, 1731, 1612, 1567.
1H NMR (301 MHz, DMSO-d6) δppm: 10.03 (s, 1H, OH), 9.65 (s, 1H, Chromene
ring), 8.51 (d, 1H, J=6 Hz, Aromatic), 8.26 (d, 1H, J=9 Hz, Aromatic), 8.08 (d,
1H, J=9 Hz, Aromatic), 7.84–7.79 (m, 1H, Aromatic), 7.75 (s, 1H, Pyridine ring),
7.68–7.61 (m, 2H, Aromatic), 7.51 (d, 2H, J = 9 Hz, Aromatic), 7.03 (br, 2H, NH2),
6.97 (d, 2H, J = 9 Hz, Aromatic).
13C NMR (76 MHz, DMSO-d6) δppm: 160.8, 159.5, 155.2, 154.2, 153.3, 139.8,
135.1, 130.5, 130.4, 130.2, 129.6, 129.5, 129.2, 127.9, 126.8, 122.7, 122.3, 117.6,
116.9, 116.2, 113.5, 112.5, 88.1.
MS (EI, 70 eV), m/z (%): 405.
2‑Amino‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)‑4‑p‑tolylnicotinonitrile (1f)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3494, 3354, 3056, 2923, 2219, 1738, 1628,
1567, 1211, 818.
1H NMR (301 MHz, DMSO-d6) δppm: 9.64 (s, 1H, Chromene ring), 8.50 (d, 1H,
J=9 Hz, Aromatic), 8.25 (d, 1H, J=9 Hz, Aromatic), 8.06 (d, 1H, J=6 Hz, Aro-
matic), 7.81 (t, 1H, J=6 Hz, Aromatic), 7.75 (s, 1H, Pyridine ring), 7.67–7.59 (m,
2H, Aromatic), 7.52 (d, 2H, J=6Hz, Aromatic), 7.39 (d, 2H, J=9 Hz Aromatic),
7.10 (br, 2H, NH2), 2.41 (s, 3H, CH3).
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Catalytic synthesis of coumarin-linked nicotinonitrile…
13C NMR (76 MHz, DMSO-d6) δppm: 160.7, 159.4, 155.2, 154.2, 153.4, 140.0,
139.8, 135.1, 134.5, 130.4, 129.9, 129.6, 129.4, 129.2, 128.5, 126.8, 122.4, 122.2,
117.3, 116.9, 113.4, 112.6, 88.4, 21.4.
MS (EI, 70 eV), m/z (%): 403.
2‑Amino‑4‑(4‑isopropylphenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1g)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3498, 3360, 3064, 2961, 2216, 1731, 1618, 1568.
1H NMR (301 MHz, DMSO-d6) δppm: 9.72 (s, 1H, Chromene ring), 8.57 (d, 1H,
J=6 Hz, Aromatic), 8.33–8.30 (m, 1H, Aromatic), 8.13 (d, 1H, J=6 Hz, Aromatic),
7.88–7.83 (m, 1H, Aromatic), 7.80 (s, 1H, Pyridine ring), 7.72–7.66 (m, 2H, Aro-
matic), 7.60 (d, 2H, J=6 Hz, Aromatic), 7.48 (d, 2H, J=6 Hz, Aromatic), 7.14 (br, 2H,
NH2), 3.02 (septet, 1H, J=6 Hz, CH). 1.31 (d, 6H, J=3 Hz, CH3).
13C NMR (76 MHz, DMSO-d6) δppm: 160.7, 159.5, 155.2, 154.3, 153.5, 150.7,
139.9, 135.1, 134.9, 130.5, 129.7, 129.5, 129.2, 128.6, 127.4, 126.9, 122.5, 122.3,
117.4, 116.9, 113.4, 112.8, 88.4, 33.8, 24.2.
MS (EI, 70 eV), m/z (%): 431.
2‑Hydroxy‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)‑4‑phenylnicotinonitrile (1h)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3415, 3054, 2228, 1725, 1651, 1605, 1582.
1H NMR (400 MHz, DMSO-d6) δppm: 12.75 (br, 1H, OH), 9.51 (s, 1H, Chromene
ring), 8.75 (br, 1H, Aromatic), 8.37 (br, 1H, Aromatic), 8.17 (br, 1H, Aromatic),
7.82–7.27 (m, 9H, Aromatic and Pyridine ring).
MS (EI, 70 eV), m/z (%): 309.
4‑(4‑Chlorophenyl)‑2‑hydroxy‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1i)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3429, 3055, 2922, 2854, 2229, 1738, 1648, 1561,
815.
1H NMR (400 MHz, DMSO-d6) δppm: 12.85 (br, 1H, OH), 9.50 (s, 1H, Chromene
ring), 8.73 (br, 1H, Aromatic), 8.37 (br, 1H, Aromatic), 8.15 (br, 1H, Aromatic),
7.79–7.72 (m, 7H, Aromatic and Pyridine ring), 7.27 (br, 1H, Aromatic).
13C NMR (76 MHz, DMSO-d6) δppm: 161.5, 158.7, 154.5, 154.4, 146.5, 141.5,
136.1, 136.0, 136, 135.2, 130.6, 130.5, 129.6, 129.5, 129.3, 127.1, 123.3, 118.3, 116.9,
116.5, 113.3, 108.8, 101.8.
MS (EI, 70 eV), m/z (%): 424.
4‑(4‑Bromophenyl)‑2‑hydroxy‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1j)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3454, 3061, 2955, 2208, 1727, 1605, 1568.
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M. Torabi et al.
1H NMR (301 MHz, DMSO-d6) δppm: 12.75 (br, 1H, OH), 9.50 (s, 1H, Chromene
ring), 8.75 (d, 1H, J=9 Hz, Aromatic), 8.37 (d, 1H, J=9 Hz, Aromatic), 8.15 (d,
1H, J=9 Hz, Aromatic), 7.87–7.85 (m, 3H, Aromatic), 7.74–7.69 (m, 4H, Aromatic
and Pyridine ring), 7.27 (br, 1H, Aromatic).
MS (EI, 70 eV), m/z (%): 469.
2‑Hydroxy‑4‑(4‑methoxyphenyl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)
nicotinonitrile (1k)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3317, 3145, 3053, 2229, 1735, 1647, 1560,
1096, 821.
1H NMR (301 MHz, DMSO-d6) δppm: 12.05 (s, 1H, OH), 9.48 (s, 1H, Chromene
ring), 8.75 (d, 1H, J=9 Hz, Aromatic), 8.36 (d, 1H, J=9 Hz, Aromatic), 8.14 (d,
1H, J=9 Hz, Aromatic), 7.84–7.68 (m, 5H, Aromatic and Pyridine ring), 7.25–7.17
(m, 3H, Aromatic), 3.88 (s, 3H, OCH3).
13C NMR (76 MHz, DMSO-d6) δppm: 161.7, 159.6, 158.7, 154.3, 145.8, 141.3,
136.0, 130.5, 130.4, 129.6, 129.5, 129.3, 128.4, 127.1, 123.3, 118.4, 117.1, 116.9,
114.9, 113.3, 108.7, 108.0, 99.4, 56.0.
MS (EI, 70 eV), m/z (%): 420.
2‑Hydroxy‑4‑(naphthalen‑2‑yl)‑6‑(3‑oxo‑3H‑benzo[f]chromen‑2‑yl)nicotinonitrile
(1l)
M.p.>300 °C, FT‐IR (KBr, ν, cm−1): 3320, 3058, 2211, 1729, 1715, 1562, 1030,
816.
1H NMR (301 MHz, DMSO-d6) δppm: 12.70 (br, 1H, OH), 9.53 (s, 1H, Chromene
ring), 8.76 (d, 1H, J=6 Hz Aromatic), 8.39–8.36 (m, 2H, Aromatic, 8.19–8.06 (m,
4H, Aromatic), 7.87–7.82(m, 2H, Aromatic), 7.73–7.65 (m, 4H, Aromatic and Pyri-
dine ring), 7.40 (br, 1H, Aromatic).
MS (EI, 70 eV), m/z (%): 440.
Acknowledgements We thank the Bu-Ali Sina University and Iran National Science Foundation [(INSF),
Grant Number: 98001912) for fnancial support to our research group.
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