Efficient Three-Component One-Pot Synthesis of 4H-Pyrans

Article abstract of DOI:10.1134/S1070428019050178

Clean, practical, and efficient electrochemical synthesis of pharmaceutically relevant 4H-pyran derivatives by one-pot three-component combination of an aryl aldehyde, malononitrile, and a dicarbonyl compoundis developed. The synthesis is performed in eth

Full text of DOI:10.1134/S1070428019050178

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 5, pp. 686–693. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 5, pp. 815.
Efficient Three-Component One-Pot Synthesis of 4H-Pyrans
a
a
a
a,
J. Malviya , S. Kala , L. K. Sharma , and R. K. P. Singh *
Electrochemical Laboratory of Green Synthesis,
Department of Chemistry, University of Allahabad, U.P., 211002 India
*
e-mail: singhrkp1@gmail.com; rkp.singh@rediffmail.com
Received November 1, 2018; revised November 18, 2018; accepted November 22, 2018
Abstract—Clean, practical, and efficient electrochemical synthesis of pharmaceutically relevant 4H-pyran
derivatives by one-pot three-component combination of an aryl aldehyde, malononitrile, and a dicarbonyl
compoundis developed. The synthesis is performed in ethanol with lithium perchlorate as a supporting
electrolyte in an undivided cell on a platinum electrode under constant potential electrolysis conditions.
Keywords: anodic oxidation, electrogererated base, Michael addition, controlled potential electrolysis (CPE),
cyclic voltammetry
DOI: 10.1134/S1070428019050178
4
H-Pyran-based heterocyclic compounds are
INTRODUCTION
privileged pharmacological scaffolds due to their
distinct structures and great potential for further
transformations into various compounds [9–12]. The
interest in these compounds is explained by their
useful pharmaceutical and biological properties,
including antiviral [13], antimicrobial [14], antifungal
[15] and anticancer activity [16].
The discovery of new synthetic methodologies that
facilitate the construction of organic compounds is a
focal point of research activity in the field of modern
organic, bioorganic, and medicinal chemistry [1]. The
concept of “privileged medicinal structures or
scaffolds” [2] has emerged as one of the guiding
principles of the drug discovery process and consist of
a rigid hetero- ring system that assumes a well-defined
orientation of appended functionalities for target
recognition [3].
The conventional method of synthesis of pyrans using
various catalysts [17] is associated with considerable
difficulties, such as complicated isolation of products,
low yields, and corrosive nature of reagents and
solvents [18–22]. The electrochemical method is quite
competitive in modern organic chemistry and offers
novel and versatile synthetic advantages. Electroche-
mical organic reactions produce electrogenerated bases
(EGBs) from methylene-active compounds employing
such a clean chemical reagent as electricity in a simple
undivided cell and provide high yields of products not
necessitating harsh conditions, such as high tempe-
ratures, large quantities of organic solvents, tedious
work-up processes, and toxic reagents. Considering the
synthetic and therapeutic significance of 4H-pyran
derivatives and proceeding with our work on the
multicomponent synthesis of heterocyclic compounds,
we designed a facile, efficient, and clean synthetic
approach to 4H-pyrans, based on the electrochemical
transformation of various aromatic aldehydes, malono-
nitrile, and dicarbonyl compounds in an undivided cell.
Multicomponent reactions (MCRs) are important
because of their wide range of applications in the
pharmaceutical industry for the rapid generation of
structurally diverse combinatorial libraries for drug
discovery [4, 5]. In addition, MCRs are
environmentally benign and atom economic, involve
no time-consuming and costly purification processes,
[
6, 7] and dramatically reduce the generation of
chemical wastes. In MCRs), three or more reactants
are combined together in a single reaction flask to
generate a product incorporating most of the atoms
contained in the starting materials [8]. These reactions
constitute an especially useful synthetic strategy
and provide mild, easy, and rapid access to large
libraries of organic molecules with diverse substitution
patterns.
6
86

EFFICIENT THREE-COMPONENT ONE-POT SYNTHESIS OF 4H-PYRANS
687
Scheme 1.
R1
CHO
O
O
O
LiClO , rt
4
CN
R1
+
CH (CN)2
2
+
R2
R2
EtOH
O
NH2
1
a_1i
2
3a, 3b
4a 4n
_
1
2
1
C
, R = H (a), p-Cl (b), m-OH (с), p-(CH
3
)
2
N (d), p-CH
3
O (e), o-Cl (f), o-CH
3
O (g), m-NO
2
3
(h), p-CH (i); 3, R = H (a),
1
2
1
2
1
2
1
2
1
2
2 5 3 2 3
H (b); 4, R = R = H (a); R = p-Cl, R = H (b); R = m-OH, R = H (c); R = p-(CH ) N, R = H (d); R = p-CH O, R =
H (e); R = o-Cl, R = H (f); R = o-CH O, R = H (g); R = m-NO , R = H (h); R = p-CH , R = H (i); R = H, R = C H
3 2 3 2 5
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
1
2
(
j); R = p-Cl, R = C
RESULTS AND DISCUSSION
In the present study we report our results on the
electrochemically induced multicomponent chain trans-
formation of acyclic 1,3-diketones, aryl aldehydes, and
malononitrile into 4H-pyrans under mild conditions by
constant potential electrolysis in an undivided cell. The
reaction was performed in alcoholic solvents with
2
H
5
(k); R = m-OH, R = C
2
H
5
(l); R = p-(CH
3
)
2
N, R = C
2
H
5
(m); R = p-CH
3 2 5
O, R = C H (n).
LiClO
as a supporting electrolyte offers a lot of
4
advantages. It is highly soluble in many organic
solvents, used as a co-catalyst in coupling reactions,
and is can be easily recovered and reused in
subsequent reactions. Ethanol as a solvent is preferable
to MeOH and n-PrOH, because it readily dissolves
both the reactants and electrolyte, and the reaction
products are easy to isolate by directs filtration after
electrolysis. The low chemical reactivity of EtOH
makes it a popular choice in cyclic voltammetry.
LiClO as an electrolyte (Scheme 1).
4
For environmental and economic reasons, we have
Further advantage of the LiClO –EtOH pair consists in
4
used a LiClO –EtOH pair in our present protocol.
its nontoxicity.
4
Table 1. Electrochemical transformation of aldehydes, malononitrile, and dicarbonyl compounds into 4H-pyrans under
constant potential electrolysis conditions
Entry
no.
Aldehyde
no.
Dicarbonyl
compound no.
2
Product
no.
Potential, V
Current density, mA/cm
Time, min
Yield, %
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
1.85
2.50
2.65
2.52
2.40
2.25
2.30
2.15
2.42
1.80
2.20
2.10
2.10
2.15
21
19
17
16
19
18
19
18
19
20
19
18
19
17
200
220
210
240
215
220
225
230
210
180
195
205
220
210
4a
4b
4c
4d
4e
4f
92
86
87
89
85
88
83
86
82
90
85
86
89
84
1g
1h
1i
4g
4h
4i
10
11
12
13
14
1j
4j
1k
1l
4k
4l
1m
1n
4m
4n
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

6
88
MALVIYA et al.
Table 2. Choice of solvent for the electrochemical synthesis of 4H-pyrans for the model reaction of benzaldehyde,
malononitrile, and acetylacetone
2
Entry no.
Solvent
Ethanol
Methanol
Acetonitrile
DMF
Potential, V
1.80
1.90
2.00
2.50
2.70
3.0
Current density, mA/cm
Yield of 4a, %
1
2
3
4
5
6
7
8
21
19
9
>90
>85
>60
>50
>40
>15
>15
>12
10
8.0
5
AcOH
DCM
Dioxane
THF
3.1
6
4.7
6
To evaluate the synthetic potential of the proposed
protocol, its scope and generality were examined with
a variety of substrates (Scheme 1, Table 1) and
optimized it for the synthesis of different 4H-pyrans.
Having optimized the solvent, we decided to check
whether the developed protocol can be extended to the
synthesis of 4H-benzo[b]pyrans using dimedone as an
alternative methylene-active reagent instead of the
linear acetylacetone (Scheme 2, Table 3). In
accordance with our expectations, these reactions
proceeded smoothly and afforded the corresponding
products in good yields.
The conversion of the starting materials into a
series of products (Table 1) with excellent yields was
performed under constant potential electrolysis
2
conditions at the current density of 16–21 mA/cm and
the quantity of electricity of 0.48–0.71 F/mol. An
increase in the potential and current density slightly
decreased the reaction yield by activating the
undesired oligomerisation of the starting materials.
The purity of the products was checked by TLC,
and their compositions and structures were
characterized by analytical, physicochemical, and
spectral (IR, H and C NMR and mass spectra) data.
The melting points and spectral characteristics of
known compounds are consistent with published
data, and the characteristics of previously unknown
compounds are presented in Experimental.
1
13
To find an appropriate medium for the synthesis of
4
H-pyrans, we performed a model reaction between
benzaldehyde (1a), malononitrile 2, and acetylacetone
a to obtain 5-acetyl-2-amino-6-methyl-4-phenyl-4H-
3
pyran-3-carbonitrile (4a) in different solvents at room
temperature (Table 2). The highest yields of about 85–
To gain insight into the mechanism of the reaction,
we employed cyclic voltammetry. The cyclic voltam-
mograms were measured for mixtures of substrates in
9
0% were obtained in ethanol, the reaction was
complete within 3–4 h, and the precipitated product
was easily separated by filtration.
EtOH–LiClO at room temperature at a scan rate of at
scan rate of 0.01 V s .
4
–
1
Scheme 2.
R
CHO
O
O
CN
CN
CN
NH2
Electrolysis
LiClO , rt
4
EtOH
O
O
R
_
1
2
4
5a 5f
R = H (1a, 5a), p-Cl (1b, 5b), p-OMe (1e, 5c), m-NO
2
(1h, 5d), p-OH (1o, 5e), p-NO
2
(1p, 5f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

EFFICIENT THREE-COMPONENT ONE-POT SYNTHESIS OF 4H-PYRANS
689
Table 3. Electrochemical synthesis of 4H-benzo[b]pyrans by the three-component reaction of aldehydes, malononitrile, and
dimedone
2
Entry no.
Aldehyde no.
Potential, V
1.80
Current density, mA/cm
Product no.
Yield, %
1
2
3
4
5
6
1a
1b
1e
1h
1o
1p
24
22
18
20
19
20
5a
5b
5c
5d
5e
5f
87
84
85
86
82
84
2.05
2.10
2.00
2.08
2.15
The cyclic voltammogram of a solution of benz-
aldehyde (1a), malononitrile 2, and acetylacetone 3a
and ethyl acetate were of analytical grade from Merck
and Fluka. Water was double distilled.
(
1 mmol each) in EtOH–LiClO exhibits two anodic
4
The melting points were measured on a Mel_Temp
capillary melting point apparatus and are uncorrected.
The IR spectra were registered on a Shimadzu 8201
peaks at 0.90 and 1.8 V and one reduction peak at 0.4
V. The anodic peaks correspond respectively to the
transformation of malononitrile and dicarbonyl
compound 3a (methylene-active compounds) into
electrogenerated bases (EGB) by removal of one
electron, which is the key step of formation of product
1
13
PC spectrometer in KBr pellets. The H and C NMR
4
a, and the reduction peak indicates the conversion of
the ethoxide ion into ethanol during electrolysis (Fig. 1).
To obtain further evidence, we measured the cyclic
voltammogram of a solution of 1-mmol aldehyde 1a
and 1 mmol of malononitrile in EtOH–LiClO . The
4
voltammogram shows a well-defined anodic peak
assignable to the formation of an EGB from
malononitrile (Fig. 2).
The mechanism of formation of substituted 4H-
pyrans is generally considered as two-step process
involving the Knoevenagel condensation of arylalde-
hydes with malononitrile followed by addition of a
dicarbonyl compound and cyclization [26]. The initial
step of the reaction is the deprotonation of malononit-
rile to form the malononitrile anion (EGB). This anion
undergoes Knovenagel condensation with aldehyde A
to form benzylidenemalononitrile B with the elimina-
tion of a water molecule [27]. Further on dicarbonyl
anion C (EGB) generated from the second methylene-
active reagent (acetylacetone, ethyl acetoacetate, or
methyl acetoacetate) reacts with intermediate B to
form Michael adduct D whose intramolecular cycliza-
tion leads to the corresponding 4H-pyran F (Scheme 3).
Fig. 1. Cyclic voltammogram of a solution of benzaldehyde,
malononitrile, and acetylacetone in 0.05 M LiClO –EtOH.
4
EXPERIMENTAL
All arylaldehydes, malononitrile, dicarbonyl
compounds, lithium perchlorate, ethanol, chloroform,
Fig. 2. Cyclic voltammogram of a solution of benzaldehyde
and malononitrile in 0.05 M LiClO –EtOH.
4
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

6
90
MALVIYA et al.
Scheme 3.
_
_
Cathod:
2EtOH
NC
NC
+
2e
2EtO
+
H2
_
O
CN
CN
O
In Solution:
Ar
Ar
C
H
+
Ar
C
H
_
A
EtO
EtOH
CN
CN
OH
C
CN
CN
H
_
H O
2
O
O
CN
_
NC
CN
CN
CN
CN
O
R
_
C
Ar
C
Ar
O
O
Ar
H
O
B
R
R
D
CN
CN
NH
2
_
NH
C
Ar
O
O
EtOH
Ar
O
O
R
R
F
R = CH , OC H , OCH .
3
2
5
3
spectra were measured with a DRX 400 (400 MHz)
spectrometer in CDCl3 or DMSO against internal
TMS. The EI mass spectra were obtained with a
Shimadzu GCMS-QP5050A instrument. The elemental
analyses were obtained on a Carlo Erba CHNS-OEA
counter electrodes and Ag/AgCl as a reference electrode
with magnetic stirring (for the applied potentials and
current densities, see Tables 1–3. The reaction progress
was monitored by TLC on silica as sorbent and hexane
with ethyl acetate as eluent. After electrolysis was
complete, the solid product was filtered off, washed
with a cold aqueous ethanol (2 × 3 mL), and dried
under reduced pressure to afford the corresponding
1
108 elemental analyser.
Cyclic voltammetry was performed on a CH Instru-
ments Model 600A electrochemical analyzer using a
traditional three-electrode cell with a platinum working
and counter electrode and an Ag/AgCl reference electrode.
4
H-pyran in an excellent yield. The purity of the
products was checked by TLC, and their compositions
and structures were characterized by analytical, physi-
cochemical, and spectral data. The melting points and
spectral characteristics of known compounds are con-
sistent with published data, and the characteristics of
previously unknown compounds are presented below.
Electrochemical synthesis of 4H-pyran deri-
vatives (general procedure). A mixture of aldehyde
(
0.53 g, 5 mmol), malononitrile (0.33 g, 5 mmol),
acetylacetone (or dimedone) (5 mmol), and LiClO4
(
0.40 g , 5mmol) in ethanol (50 mL) was electrolyzed
under constant potential conditions (Table 1) [23, 24]
at room temperature for 3–4 h in an undivided cell
assembly with platinum plates (1 cm ) as working and
5-Acetyl-2-amino-6-methyl-4-phenyl-4H-pyran-
3-carbonitrile (4a), mp 195–197°C {published data:
mp 193–195°C [28(b)]}.
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

EFFICIENT THREE-COMPONENT ONE-POT SYNTHESIS OF 4H-PYRANS
691
5
-Acetyl-2-amino-6-methyl-4-(4-chlorophenyl)-
M.w. 284.31, mp 190–192°C. IR spectrum (KBr), ν,
–
1
1
4
2
1
H-pyran-3-carbonitrile (4b). C H ClN O , M.w.
88.73, mp 135–137°C. IR spectrum (KBr), ν, cm :
665 (C=O), 2194 (C≡N), 3333(NH ). H NMR spec-
cm : 1690 (C=O), 2205 (C≡N), 3340 (NH ). H NMR
1
5
13
2
2
2
–
1
spectrum (400 MHz, DMSO-d ), δ, ppm: 1.72 s (3H,
6
1
CH ), 2.30 s (3H, CO–CH ), 3.73 s (3H, OCH ), 4.95 s
2
3
3
3
trum (400 MHz, DMSO-d ), δ, ppm: 1.85 s (3H, CH ),
(1H, CH), 6.89 br.s (2H, NH ), 6.65–6.66 m (2H, Ar),
6.95–6.96 m (2H, Ar). C NMR spectrum (100 MHz,
6
3
2
1
3
2
.12 s (3H, COCH ), 4.25 s (1H, CH), 6.75 s (2H,
3
1
3
NH ), 6.90 d (2H, Ar), 7.14 d (2H, Ar). C NMR
DMSO-d ), δ, ppm: 17.4, 29.9, 30.2, 57.2, 58.1, 115.2,
2
6
spectrum (100 MHz, DMSO-d ), δ, ppm: 18.8, 29.6,
119.3, 120, 122.0, 122.4, 128.8, 130.4, 159.7, 154.3,
159.3, 198.5.
6
3
1
8.2, 57.5, 114.9, 120.2, 128.8, 129.4, 129.4, 130.2,
31.8, 143.7 155.3, 158.2, 198.5.
5
-Acetyl-2-amino-6-methyl-4-(3-nitrophenyl)-
5
-Acetyl-2-amino-6-methyl-4-(3-hydroxy-phe-
4H-pyran-3-carbonitrile (4h), mp 168–170°C
nyl)-4H-pyran-3-carbonitrile (4c). C H N O . M.w.
{published data: mp 161–162°C [28(b)]}.
1
5
14
2
3
–
1
2
1
70.28, mp 165–167°C. IR spectrum (KBr), ν, cm :
666 (C=O), 2196 (C≡N), 3337 (NH2). H NMR
5
-Acetyl-2-amino-6-methyl-4-p-tolyl-4H-pyran-
1
3
-carbonitrile (4i), mp 190–192°C {published data:
spectrum (400 MHz, DMSO-d ), δ, ppm: 1.85 s (3H,
6
mp 274–276°C [28(b)]}.
CH ), 1.95 m (3H, CO–CH ), 4.17 s (1H, CH), 6.35–
3
3
Ethyl 6-amino-5-cyano-2-methyl-4-phenyl-4H-
pyran-3-carboxylate (4j), mp 197–199°C {published
data: mp 194–196°C [28(a)]}.
6
9
.40 m (3H, Ar), 6.67 s (2H, NH ) 6.92 t (1H, Ar),
.28 s (1H, Ph–OH). C NMR spectrum (100 MHz,
2
1
3
DMSO-d ), δ, ppm: 18.8, 29.5, 39.7, 59.7, 114.9, 115,
6
1
1
15.9, 118.7, 120.8, 129.7, 146.5, 155.6, 157.8, 158.9,
98.8.
Ethyl 6-amino-4-(4-chlorophenyl)-5-cyano-2-me-
thyl-4H-pyran-3-carboxylate (4k), mp 178–180°C
{
published data: mp 173–174°C [28(a)]}.
5
-Acetyl-2-amino-4-[4-(dimethylamino)phenyl]-
6
-methyl-4H-pyran-3-carbonitrile (4d). C H N O .
1
7
19
3
2
Ethyl 6-amino-4-(3-hydroxyphenyl)-5-cyano-2-
methyl-4H-pyran-3-carboxylate (4l), mp 167–169°C
published data: mp 161–162°C [28(a)]}.
M.w. 297.35, mp 178–180°C. IR spectrum (KBr), ν,
cm : 1665 (C=O), 2199 (C≡N), 3339 (NH ). H NMR
spectrum (400 MHz, DMSO-d ), δ, ppm: 1.71–1.78 s
–
1
1
2
{
6
Ethyl 6-amino-4-(4-(dimethylamino)phenyl)-5-
cyano-2-methyl-4H-pyran-3-carboxylate (4m).
(
6H, CH ) 2.32 s (3H, –CO–CH ), 2.85 m (3H, CH ),
3 3 3
3
.94 s (1H, CH), 6.47–6.88 m (4H, Ar), 6.82 s (2H,
1
3
C H N O . M.w. 327.38, mp 174–176°C. IR
1
8
21
3
3
NH2). C NMR spectrum (100 MHz, DMSO-d ), δ,
ppm: 18.3, 29.7, 38.6, 41.3, 57.7, 114.2, 114.5, 114.8,
1
1
6
–
1
spectrum (KBr), ν, cm : 1665 (C=O), 2199 (C≡N),
339 (NH ). H NMR spectrum (400 MHz, DMSO-
1
3
2
17.7, 119.8, 130, 132.5, 146.5, 157.6, 158.2, 159.8,
98.4.
d ), δ, ppm: 1.08–1.12 m (6H, CH ), 1.71 s (3H, CH ),
6
3
3
3
6
.82 s (1H, CH), 4.15 m (2H, CH ), 4.94 s (2H, NH ),
2 2
1
3
5
-Acetyl-2-amino-4-(4-methoxyphenyl)-6-me-
.47–6.88 m (4H, Ar). C NMR spectrum (100 MHz,
thyl-4H-pyran-3-carbonitrile (4e), mp 184–187°C
DMSO-d ), δ, ppm: 16.4, 18.3, 38.6, 41.3, 41.5, 57.7,
6
{
published data: mp 210–213°C [28(b)]}.
-Acetyl-2-amino-4-(2-chlorophenyl)-6-methyl-
6
1
3.1, 107.5, 114.8, 117.7, 119.8, 130, 130.2, 132.5,
46.5, 157.6, 158.2, 168.4.
5
4
2
1
H-pyran-3-carbonitrile (4f). C H ClN O. M.w.
15 13 2
Ethyl-6-amino-4-(4-methoxyphenyl)-5-cyano-2-
methyl-4H-pyran-3-carboxylate (4n), mp 180–182°C
{published data: mp 135–136°C [28(a)]}.
–
1
88.73, mp 203–205°C. IR spectrum (KBr), ν, cm :
1
693(C=O), 2202 (C≡N), 3339 (NH2). H NMR
spectrum (400 MHz, DMSO-d ), δ, ppm: 2.01 s (3H,
CH ), 2.21 s (3H, CH ), 4.93 s (1H, CH), 6.89 br.s
6
2
-Amino-5,6,7,8-tetrahydro-7,7-dimethyl-5-oxo-
3
3
4
-phenyl-4H-chromene-3-carbonitrile (5a), mp 235°C
{published data: mp 230–232°C [25(a)]}.
(
2H, NH ), 7.14–7.16 m (1H, Ar), 7.21–7.23 m (1H,
2
13
Ar), 7.27–7.29 m (1H, Ar), 7.37–7.39 m (1H, Ar).
C
NMR spectrum (100 MHz, DMSO-d ), δ, ppm: 18.4,
2-Amino-4-(4-chlorophenyl)-5,6,7,8-tetrahydro-
7,7-dimethyl-5-oxo-4H-chromene-3-carbonitrile (5b),
mp 219°C {published data: mp 215–217°C [25(b)]}.
6
2
1
9.9, 36.2, 58.1, 115.3, 119.3, 128.8, 129.2, 130.4,
32.2, 136.8, 143.7, 154.3, 159.3, 198.5.
5
-Acetyl-2-amino-4-(2-methoxyphenyl)-6-me-
2-Amino-5,6,7,8-tetrahydro-4-(4-methoxy-
thyl-4H-pyran-3-carbonitrile (4g). C H N O .
phenyl)-7,7-dimethyl-5-oxo-4H-chromene-3-carbo-
1
6
16
2
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 5 2019

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MALVIYA et al.
nitrile (5c), mp 199°C {published data: mp 200–203°C
5. Terret, N.K., Gardner, M., Gordon, D.W., and
Kobylecki, R.J., Tetrahedron, 1995, vol. 51, p. 8135.
[28(b)]}.
6. Wender, P.A., Handy, S.T., and Wright, D.L., Chem.
2-Amino-5,6,7,8-tetrahydro-7,7-dimethyl-4-(3-nit-
Ind., 1997, vol. 765, p. 767.
rophenyl)-5-oxo-4H-chromene-3-carbonitrile (5d),
mp 220°C {published data: mp 215–217°C [25(b)]}.
7
8
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2
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9. Martin, N., Pascual, C., Seoane, C., and Soto, J.L.,
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10. Adbel-Fattah, A.H., Hesien, A.M., Metwally, S.A., and
[25(b)]}.
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1
1
1
1. Quintela, J.M., Peinador, C., and Moreira, M.J.,
2
-Amino-5,6,7,8-tetrahydro-7,7-dimethyl-4-(4-nit-
Tetrahedron, 1995, vol. 51, p. 5901.
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Chem Sect B, 1996, vol. 35B, p. 602.
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Motoniro, S., Junji, N., and Masayosh, K., PCT Int.
Appl., JP2009179589 (A), 2009.
rophenyl)-5-oxo-4-phenyl-4H-chromene-3-carbo-
nitrile (5f), mp 185°C {published data: mp 186–188°C
25(a)]}.
[
CONCLUSION
In summary, we have developed a simple, mild,
1
1
4. Kitamura, R.O.S.P., Romoff, M.C.M., Young, M.J., and
Kato, J.H.G., Phytochem. 2006, vol. 67, p. 2398.
green, and sustainable synthesis of a series of
biologically and pharmacologically important 4H-
pyran derivatives. This novel electrocatalytic chain
process offers an efficient and convenient way to
produce 4H-pyran derivatives in excellent yields. The
notable highlights of this protocol are operational
simplicity, wide substrate scope, excellent functional
group tolerance, environmental safety, mild reaction
conditions, easy workup, high yields, short reaction
time, and easy handling. The developed methodology
represents a novel synthetic concept for multicom-
ponent reactions and brings us a step closer to the
notation of “ideal synthesis” [6, 28].
5. Tangmouo, J.G., Meli, A.L., Komguem, J., Kuete, V.,
Ngounou, F.N., Lontsi, D., Beng, V.P., Choudhary, M.I.,
and Sondengam, B.L., Tetrahedron Lett., 2006, vol. 47,
p. 3067. doi 10.1016/j.tetlet.2006.03.006
6. Cocco, M.T., Congiu, C., and Onnis, V., Bioorg. Med.
Chem., 2003, vol. 11, p. 495.
1
1
7. (a) Ballini, R., Bosica, G., Conforti, M.L., Maggi, R.,
Mazzacani, A., Righi, P., and Sartori, G., Tetrahedron,
2
001, vol. 57, p. 1395. (b) Pratap, U.R., Jawale, D.V.,
Netankar, P.D., and Mane, R.A., Tetrahedron Lett.,
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1
8. (a) Li, Y., Chen, H., Shi, C., Shi, D., and Ji, S., J. Comb.
Chem., 2010, vol. 12, p. 231. (b) Devi, I. and Bhuyan, P.J.,
Tetrahedron Lett., 2004, vol. 45, p. 8625. (c) Akbarzadeh, T.,
Rafinejad, A., Mollaghasem, J.M., and Safari, M., Arch.
Pharm. Chem. Life Sci., 2012, vol. 345, p. 386.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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