The clean synthesis and confirmatory structural characterization of new 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano based on Kojic acid

Article abstract of DOI:10.1007/s00706-018-2254-3

Abstract: A valuable and clean method was developed for the synthesis of the group of different novel 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitriles containing a 2-aminopyran moiety by using of azido kojic acid and various 2-arylidinemalononitriles in the presence of NH₄Cl as a catalyst in a green solvent (ethanol) with excellent yields. All structures were analyzed by FT-IR, ¹H, ¹³C NMR spectroscopy, and representatively, one compound was analyzed by X-ray crystallography technique. Crystallographic analyses indicated that of this compound a dimer formed via two weak intermolecular hydrogen bonds with d_(N···O) distances of 2.927?? and made a 14-membered ring with centrosymmetric (C_i) form. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-018-2254-3

Monatshefte für Chemie - Chemical Monthly
https://doi.org/10.1007/s00706-018-2254-3(0123456789(). -, vo Vl
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ORIGINAL PAPER
The clean synthesis and confirmatory structural characterization
of new 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano based
on Kojic acid
Khadijeh Ojaghi Aghbash1 Nader Noroozi Pesyan1
Behrouz Notash2
•
•
Received: 26 February 2018 / Accepted: 11 June 2018
Ó Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract
A valuable and clean method was developed for the synthesis of the group of different novel 2-amino-4,8-dihydropy-
rano[3,2-b]pyran-3-carbonitriles containing a 2-aminopyran moiety by using of azido kojic acid and various 2-ary-
lidinemalononitriles in the presence of NH4Cl as a catalyst in a green solvent (ethanol) with excellent yields. All structures
were analyzed by FT-IR, 1H, 13C NMR spectroscopy, and representatively, one compound was analyzed by X-ray
crystallography technique. Crystallographic analyses indicated that of this compound a dimer formed via two weak
˚
intermolecular hydrogen bonds with d(NÁÁÁO) distances of 2.927 A and made a 14-membered ring with centrosymmetric (Ci)
form.
Graphical abstract
Keywords Kojic acid Á Azido kojic acid Á Michael addition Á Pyran Á 2-Amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile
Introduction
ranging of pharmacological [1] and biological activities
and endure attracting attention [2–4]. Pyrans and poly-
substituted pyrans due to their numerous medicinal and
biological actions such as antioxidant [5], anticancer [6, 7],
anti-inflammatory and antiviral [8], antibacterial [9],
antimicrobial [10], anti-HIV [11], antifungal [12], and
calcium channel antagonist activities [13] have received far
interest.
Pyrans are one of the main series of heterocyclic six-
membered compounds including oxygen. Pyran products
constitute a key structural motif of numerous biologically
active natural and synthetic compounds which own a wide
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s00706-018-2254-3) contains
supplementary material, which is available to authorized
users.
A number of 2-aminopyrans are utilized in pigments
[14] and photoactive resources [15] and also used as
potentially bio-decomposable agrochemicals [16, 17].
Polyfunctionalized 2-amino-4H-pyran-3-cyano derivatives
are the main heterocyclic compounds, which often show a
range of biological actions [18–28]. Bispyrans show great
colorability, as well as moral fatigue resistance and also are
used as new photochromic dyes for the preparation of
& Nader Noroozi Pesyan
n.noroozi@urmia.ac.ir; nnp403@gmail.com
1
Department of Organic Chemistry, Faculty of Chemistry,
Urmia University, Urmia, Iran
2
Department of Chemistry, Faculty of Science, Shahid
Beheshti University, Tehran, Iran
123

K. O. Aghbash et al.
resources with uses in the modulation of fluorescence, fil-
ter, and display [29].
The reaction of 2 with Knoevenagel adducts 3 afforded
2-amino-6-(azidomethyl)-8-oxo-4-aryl-4,8-dihydropy-
1
rano[3,2-b]pyran-3-carbonitriles 4. H NMR spectra and
Kojic acid is a by-product of the fermentation of the
saccharose, glucose, starch, etc., by different microorgan-
isms (Aspergillus, Penicillium, and Acetobacter) in an
aerobic process [30–32]. Kojic acid (KA) and some of its
derivatives are an important category of the structural motif
of many compounds (natural and synthetic), which possess
high activity outline due to their wide series of biological
actions as tyrosinase inhibitory activities [33, 34],
antimelanogenic [35], antimicrobial [36], whitening agent
[37], anti-inflammatory [38], antineoplastic [39], antiviral
and anticonvulsant [40], antifungal and antibacterial [41],
antioxidant [42], and depigmenting [43]. Pyrano[3,2-
b]pyrans are of more notice in the synthesis of organic
compounds, and numerous ways consuming diverse
homogeneous and heterogeneous catalysts have been
described for the manufacture of derivatives of KA
[9, 19, 44–52].
X-ray crystallographic analysis data (see later) confirmed
the formation of 4 (Scheme 1 and experimental data).
Representatively, FT-IR spectrum of 4a showed broad
peaks at the frequencies of 3387 and 3314 cm-1 that cor-
responded to NH2 functional group, respectively, and two
sharp peaks at 2193 and 2112 cm-1 were of nitrile and
azide groups. A sharp peak at 1643 cm-1 corresponded to
1
pyrone carbonyl group. H NMR spectrum of this com-
pound showed doublet of doublet at d = 4.23–4.37 ppm
which corresponded to diastereotopic methylene protons
connected to azide substituent. A singlet at 4.82 ppm is of
benzylic methine proton in the chiral center. The peak of
amino protons is overlapped at aromatic peaks region.
Other proton’s peaks had good agreement with the assigned
structure. 13C NMR spectrum of 4a showed 14 distinct
peaks that confirmed the proposed structure. Two peaks at
d = 56.077 and 50.209 ppm corresponded to methylene
and methine carbon atoms, respectively (see experimental
section and Supplementary data). A possible mechanism
for the production of 2-amino-6-(azidomethyl)-8-oxo-4-
phenyl-4,8-dihydropyrano[3,2-b]pyran-3-carbonitriles 4a–
4l is shown in Scheme 2 [21, 58, 59].
Recently, some approaches have been published for the
efficient and facile synthesis of polysubstituted 2-amino-
4H-pyran-3-cyano supports [53]. Among these compounds,
probable biological activity, great reactivity, and the ready
accessibility of kojic acid make it a nice-looking molecule
in pharmacological chemistry and synthetic reactions
[20, 54]. The blend of two main structures such as pyran
and kojic acid can lead to novel and substitute drug nom-
inees with an enhanced pharmacological outline. In asso-
ciation with our attention in the product of heterocyclic
derivatives [42, 55] and the wide spectrum of uses of
pyrans, 2-aminopyrans, 2-amino-4H-pyran-3-cyano, bis-
pyrans, and kojic acid as biologically active compounds,
we became concerned in the synthesis of different
2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitriles
from azido kojic acid with various alkenes (2-arylidene-
malononitrile). Also, we present a safe, efficient, and clean
method for the construction of new 2-amino-6-(azido-
methyl)-8-oxo-4-aryl-4,8-dihydropyrano[3,2-b]pyran-3-
carbonitrile derivatives from azido kojic acid with various
alkenes in ethanol as a clean solvent.
First, enolate of azido kojic acid 2 corresponding to
Knoevenagel adduct 3 is added via Michael addition which
formed intermediate A. The 1,3-proton shift formed inter-
mediate B and then, with a nucleophilic attack of oxygen
enolate anion of intermediate B to nitrile group formed
intermediate C. Finally, 1,3-proton shift to the nitrogen
anion obtained more stable compounds 4.
As shown in Table 1, in the item of alkenes with elec-
tron-withdrawing groups such as 4b, 4c, 4d, 4i, and 4k, the
time of reaction was short and the yields of the reaction
were excellent. In contrast, in the case of alkenes with
electron-donating groups such as 4e, 4f, 4g, 4h, 4j, and 4l,
the time of reaction was long and the yields of the reaction
were good. We performed the reaction of azido KA 2 with
the Knoevenagel adducts 5–7 in which derived from the
condensation reaction of malononitrile and ethyl
cyanoacetate with various aromatic aldehydes. No expec-
ted compounds 8 and 9 were observed. In the case of the
alkenes 6 and 10, there was no product due to the high
resonance of alkene double bond [60] that would not allow
Michael addition (Fig. 1).
Results and discussion
Initially, the reaction of KA (1) with SOCl2 (thionyl
chloride) at room temperature formed chloro kojic acid [2-
(chloromethyl)-5-hydroxy-4H-pyran-4-one] [56], then fol-
lowed 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (2) in
the reaction with sodium azide (NaN3) in dry DMF [57]. A
strong absorption band at 2109 cm-1 matching to the azide
group in the FT-IR spectra of the azide compound 2 was
displayed (Scheme 1).
For the more investigation of the synthetic compound
structure, the crystal structure analysis of 4c was under-
taken. The ORTEP diagram and crystal packing chart of 4c
are, respectively, shown in Figs. 2 and 3. Crystallographic
data, angles, torsion angles, and selected bond lengths are,
respectively, displayed in Tables 2 and 3.
123

The clean synthesis and confirmatory structural characterization of new 2-amino-4,8-dihydro…
Scheme 1
Scheme 2
In
2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano
double bond distances confirmed this resonance with
judging to the double-bond distances of C7=C8, C5=C6,
and C2=C3. As it could be seen, the bond distance of
˚
C7=C8 (1.362(3) A) was longer than that of C5=C6
˚
(1.342(3) A) which indicated the resonance and conjuga-
fused ring of compound 4c, the 4H-pyran-4-one ring
moiety was planar and the fused 4H-pyran ring was dis-
torted and had little boat form. For instance, the torsion
angles O3–C7–C8–C10 and O3–C5–C6–C10 were equal to
6.3(4)° and 2.4(3)°, respectively (Table 3, entries 21 and
22). These observations were indicated the non-planarity of
tion of cyano and amino groups. Other evidence for this
resonance effect was the near planarity of –NH2 group with
the –CN group on the double bond. The dihedral angle of
N4–C7–C8–C9 equals to 6.8 (4)° (Table 3, entry 24). The
2-amino-4,8-dihydropyrano[3,2-b]pyran-3-cyano
fused
ring. Amino group had resonance with the cyano group on
˚
the 4H-pyran ring moiety due to the conjugation. The C=C
bond distance of C2=C3 (1.340(4) A) was shorter than that
123

K. O. Aghbash et al.
Table 1 Reaction time and
yields for the synthesis of 4
bond of C4=O2ÁÁÁÁH4B–N4 and donor-acceptor (dNÁÁÁO
)
Compd.
Time/h
Yield/%
˚
distances were respectively obtained 2.104 and 2.927 A.
4a
4b
4c
4d
4e
4f
16
12
14
12
24
20
20
20
12
17
12
20
99
99
97
98
90
96
92
92
98
90
97
94
˚
Based on bar chart of d(OÁÁÁO) distances (d, A) in organic
compounds, subdivided into hydrogen bond strength sub-
˚
classes, the d(NÁÁÁO) distances of 2.927 A is attributed to
weak intermolecular hydrogen bond [61, 62]. The com-
pound 4c formed a dimer form via two intermolecular
hydrogen bonds between C4=O2ÁÁÁÁH4B–N4 atoms with
˚
4g
4h
4i
d
(NÁÁÁO) distances of 2.927 A and made a 14-membered ring
with centrosymmetric (Ci) form (Fig. 4, Table 4).
4j
Conclusion
4k
4l
In the current study, we have reported a safe, efficient, and
clean process for the synthesis of 2-amino-6-(azidomethyl)-
4-(4-aryl)-8-oxo-4,8-dihydropyrano[3,2-b]pyran-3-carboni-
trile by the use of different alkenes with 2-(azidomethyl)-5-
hydroxy-4H-pyran-4-one in excellent yields. It was estab-
lished that the usage of alkenes with electron-withdrawing
groups in ethanol as a green solvent via Michael addition of
2-(azidomethyl)-5-hydroxy-4H-pyran-4-one rises the reac-
tion yield and decreases the reaction time in comparison to
the same reaction with other alkenes with electron releasing
groups. Representatively, crystallographic analyses of
compound 4c showed two weak intermolecular hydrogen
bonds between two structures and formed a 14-membered
ring with centrosymmetric (Ci) form.
Experimental
All used material were purchased from Fluka or Merck
companies. The structure of compounds was drawn and
nomenclature by ChemDraw Ultra 15 version software.
Melting points were evaluated with an Electro-thermal (nu-
merical melting point device). FT-IR spectra of the synthetic
compound were confirmed by making KBr pills in area
400–4000 cm-1 on a NEXUS 670 FT-IR spectrometer
(Urmia University, Urmia, Iran). The 1H and 13C NMR
spectra were documented at 300 and 75 MHz on Bruker 300
Fig. 1 Formula structures of Knoevenagel adducts 3, 5–7, and 10 and
unfavored compounds 8 and 9
1
FT-NMR, one-to-one (Urmia University, Urmia, Iran). H
and 13C NMR spectra were achieved on a solution in CDCl3
and DMSO-d6 as solvents using TMS as an internal standard.
The information is informed as bs = broad singlet,
m = multiplet or unresolved, t = triplet, d = doublet, and
s = singlet, coupling constant(s) in Hz, integration. All
reactions were controlled by TLC (silica gel-converted
plates). Mass data were measured on Agilent Technology
(HP), MS model: 5973 Network Mass Selective Detector, ion
source: electron impact (EI) 70 eV, ion source temperature:
230 °C, analyzer: quadrupole, analyzer temperature: 230 °C.
of two other C=C double bonds and indicated no resonance
of this bond (Table 3 and supplementary data). The phenyl
ring was not perpendicular with the 4H-pyran ring moiety.
The dihedral angle of C8–C10–C11–C16 was equal to
- 34.4 (3)° (Table 3, entry 25). The azido group (N1–N2–
N3) did not lie linear due to the angle of 168.8(4)°
(Table 3, entry 13). One of the interesting phenomena in
this structure was the existence of two intermolecular
hydrogen bonds between two structures. The hydrogen
123

The clean synthesis and confirmatory structural characterization of new 2-amino-4,8-dihydro…
Fig. 2 ORTEP diagram of 4c
compound 2 as yellow solid, with 0.73 g (70%) yield.
M.p.: 131–132 °C. The analytical data are matching with
the one previously described [57].
General procedure for the preparation of various
Knoevenagel adducts of 2-benzylidenemalononitrile
and ethyl 2-cyano-3-aryl acrylate (3 and 5–7)
To a solution of 1 mmol ethyl cyanoacetate or malononi-
trile and 20 cm3 NaOH (2%), a solution of various alde-
hydes (1 mmol) in 5 cm3 ethanol was added. Then, the
mixture of the reaction was heated at 60 °C. The resulting
precipitate was filtrated and dried under reduced pressure
to give the crude product 3 and 5–7 which was purified by
recrystallization from EtOH.
Fig. 3 Crystal packing diagram of 4c
2-(Azidomethyl)-5-hydroxy-4H-pyran-4-one (2, C6H5N3O3) To
a suspension of 0.39 g sodium azide (6 mmol) in 4 cm3 dry
DMF, 1 g 2-(chloromethyl)-5-hydroxy-4H-pyran-4-one
(6 mmol) was added and the mixture for 24 h under inert
gas at room temperature was stirred. Then, cold water was
added to a reaction mixture. As the water increased, the
colored cream precipitates were formed. The filtered pre-
cipitates were dried under vacuum. The rudimentary pro-
duct with ethyl acetate was recrystallized to give azide
General procedure for the synthesis of 2-amino-6-
(azidomethyl)-8-oxo-4-aryl-4,8-dihydropyrano
[3,2-b]pyran-3-carbonitriles 4a–4l
Azido kojic acid 2 (1 mmol) and various Knoevenagel
adducts 3 (1 mmol) in 5 cm3 dry ethanol were solved.
After adding ammonium chloride (30 mol%), the mixture
was refluxed for 12–24 h. After achievement of the reac-
tion, the mixture was evaporated with rotary set and the
123

K. O. Aghbash et al.
Table 2 Crystallographic data for 4c
˚
Table 3 Selected bond lengths (d/A), angles (h/°), and torsion angles
(u/°) for 4c
Chemical formula
C16H9Cl2N5O3
˚
Mr
390.18
Entry
Atom
d/A, h/°, u/°
Crystal system, space group
Monoclinic, P21/n
1
O1–C2
1.357(3)
1.353(3)
1.233(3)
1.371(3)
1.421(4)
1.340(4)
1.342(3)
1.362(3)
1.121(4)
1.217(3)
1.141(4)
1.332(3)
168.8(4)
115.7(3)
114.1(2)
107.0(2)
119.3(2)
112.1(2)
- 1.6(4)
- 167.63(18)
6.3(4)
T/K
298
2
O1–C6
˚
a, b, c /A
10.557(2), 6.7419(13), 23.419(5)
3
O2–C4
b/°
100.32(3)
1639.9(6)
4
4
O3–C7
3
˚
V/A
5
C8–C9
Z
6
C2–C3
˚
Radiation type
l/mm-1
Mo Ka, k = 0.71073 A
7
C5–C6
0.43
8
C7–C8
Crystal size/mm
F(000)
0.40 9 0.40 9 0.20
9
N1–N2
792
1.580 Mg m-3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
N2–N3
Dx
N5–C9
Data collection
Diffractometer
N4–C7
STOE IPDS 2T
0.849, 0.920
N1–N2–N3
N2–N3–C1
C8–C10–C11
C6–C10–C8
C6–O1–C2
N3–C1–C2
O1–C2–C3–C4
O1–C6–C10–C8
O3–C7–C8–C10
O3–C5–C6–C10
N3–C1–C2–O1
N4–C7–C8–C9
C8–C10–C11–C16
C10–C11–C12–C13
Tmin, Tmax
No. of measured, independent
and observed [I [ 2r(I)]
reflections
10513, 4380, 2742
Rint
0.063
0.686
-1
˚
(sin h/k)max /A
Refinement
R[F2 [ 2r(F2)], wR(F2), S
No. of reflections
No. of parameters
H-atom treatment
0.047, 0.157, 0.98
4380
241
- 2.4(3)
- 89.2(3)
6.8(4)
H atoms treated by a mixture of
independent and constrained
refinement
- 34.4(3)
173.6(2)
-3
˚
Dqmax, Dqmin/e A
0.37, - 0.41
resultant precipitate was recrystallized for purification in
methanol:acetonitrile (1:1).
2-Amino-6-(azidomethyl)-8-oxo-4-phenyl-4,8-dihydropyrano[3,2-
b]pyran-3-carbonitrile (4a, C16H11N5O3) Cream solid; yield
ꢀ
0.32 g (99%); m.p.: 207–209 °C; FT-IR (KBr): m = 3387
and 3314 (–NH2), 3204, 3068, 2929, 2331, 2193 (–CN),
2112 (–N3), 1643 (pyrone-CO), 1601, 1426, 1271, 1210,
1
1082, 1011, 860, 704 cm-1; H NMR (300 MHz, DMSO-
d6): d = 4.23–4.37 (dd, 2H, –CH2N3), 4.82 (s, 1H, –CH-
chiral), 6.46 (s, 1H, pyrone-H), 7.24–7.41 (m, 7H, NH2,
H-Ph) ppm; 13C NMR (75 MHz, DMSO-d6): d = 50.2 (C-
chiral), 56.0 (–CH2N3), 114.5, 119.6, 128.2, 129.4, 136.9,
140.9, 150.0, 159.6, 162.5, 169.8 (pyrone-CO) ppm; MS:
m/z (%) = 321 (M?, 100), 244 (97), 216 (40).
Fig. 4 Two intermolecular hydrogen bonds of 4c. Formation of the
14-membered ring with centrosymmetric Ci form and assigned with a
dense dot (blue circle) (color figure online)
2-Amino-6-(azidomethyl)-4-(3-nitrophenyl)-8-oxo-4,8-dihydropy-
rano[3,2-b]pyran-3-carbonitrile (4b, C16H10N6O5) Yellow
solid; yield 0.36 g (99%); m.p.: 213–215 °C; FT-IR (KBr):
(300 MHz, DMSO-d6): d = 4.19–4.38 (dd, 2H, –CH2N3),
5.17 (s, 1H, –CH-chiral), 6.47 (s, 1H, pyrone-H), 7.40 (s,
2H, NH2), 7.68–7.73 (m, 1H, H-Ph), 7.82–7.85(m, 1H,
H-Ph), 8.20 (s, 2H, H-Ph) ppm; 13C NMR (75 MHz,
DMSO-d6): d = 50.0 (C-chiral), 55.0 (–CH2N3), 114.6,
ꢀ
m = 3380 and 3321 (–NH2), 3206, 3074, 2916, 2316, 2190
(–CN), 2107 (–N3), 1645 (pyrone-CO), 1547, 1427, 1345,
;
1306, 1211, 1086, 1022, 879, 680 cm-1 1H NMR
123

The clean synthesis and confirmatory structural characterization of new 2-amino-4,8-dihydro…
Table 4 Hydrogen bond
geometries in the crystal
D–HÁÁÁA
d(D–H)
d(HÁÁÁA)
d(DÁÁÁA)
\ (DHA)
Directionality
Weak
N(4)–H(4B)ÁÁÁO(2)a
0.828
2.104
2.927
173.36
structure of 4c
aSymmetry code: -x, 2 - y, -z
ꢀ
119.4, 122.3, 124.4, 137.1, 142.9, 148.5, 159.8, 162.6,
169.8 (pyrone-CO) ppm; MS: m/z (%) = 366 (M?, 77), 244
(100), 216 (50).
m = 3382 and 3316 (–NH2), 3205, 2945, 2846, 2330, 2192
(–CN), 2111 (–N3), 1648 (pyrone-CO), 1598, 1424, 1265,
1
1209, 1108, 1021, 859, 629 cm-1; H NMR (300 MHz,
DMSO-d6): d = 3.74 (s, 3H, –OMe), 4.23–4.36 (dd, 2H, –
CH2N3), 5.03 (s, 1H, –CH-chiral), 6.46 (s, 1H, pyrone-H),
6.92–7.37 (7H, –NH2, H-Ph) ppm; 13C NMR (75 MHz,
DMSO-d6): d = 50.1 (C-chiral), 55.6 (–CH2N3), 56.7 (–
OCH3), 114.5, 119.7, 128.5, 129.1, 130.6, 137.4, 150.5,
157.5, 159.9, 162.3, 169.8 (pyrone-CO) ppm.
2-Amino-6-(azidomethyl)-4-(2,4-dichlorophenyl)-8-oxo-4,8-di-
hydropyrano[3,2-b]pyran-3-carbonitrile (4c, C16H9Cl2N5O3)-
Cream solid; yield 0.38 g (97%); m.p.: 203–205 °C; FT-IR
(KBr): m = 3390 and 3313 (–NH2), 3189, 2308, 2197
(–CN), 2108 (–N3), 1645 (pyrone-CO), 1421, 1212, 1094,
1024, 861, 674 cm-1 1H NMR (300 MHz, DMSO-d6):
;
ꢀ
d = 4.21–4.36 (dd, 2H, –CH2N3), 5.32 (s, 1H, –CH-chiral),
6.48 (s, 1H, pyrone-H), 7.34 (s, 2H, NH2), 7.43–7.5 (m, 2H,
H-Ph), 7.6 (s, 1H, H-Ph) ppm; 13C NMR (75 MHz, DMSO-
d6): d = 50.0 (C-chiral), 54.5 (–CH2N3), 114.6, 119.1,
128.5, 131.1, 133.9, 134.1, 136.6, 137.5, 148.5, 159.8,
162.6, 169.7 (pyrone-CO) ppm; MS: m/z (%) = 390 (M?,
21), 389 (55), 244 (100), 216 (50).
2-Amino-6-(azidomethyl)-4-(4-hydroxyphenyl)-8-oxo-4,8-dihy-
dropyrano[3,2-b]pyran-3-carbonitrile (4g, C16H11N5O4) Yel-
low solid; yield 0.31 g (92%); m.p.: 209–211 °C; FT-IR
ꢀ
(KBr): m = 3317 (–NH2), 3177, 2676, 2321, 2203 (–CN),
2111 (–N3), 1645 (pyrone-CO), 1604, 1427, 1365, 1262,
1
1216, 1019, 864, 661 cm-1; H NMR (300 MHz, DMSO-
d6): d = 4.25–4.38 (dd, 2H, –CH2N3), 4.67 (s, 1H, –CH-
chiral), 6.45 (s, 1H, pyrone-H), 6.74–6.77 (d, J = 8.4, 2H,
H-Ph), 7.06–7.09 (d, J = 8.4, 2H, H-Ph), 7.17 (s, 2H, NH2),
9.47 (s, 1H, OH) ppm; 13C NMR (75 MHz, DMSO-d6):
d = 50.1 (C-chiral), 55.6 (–CH2N3), 116.1, 119.7, 131.2,
136.6, 150.5, 157.5, 159.5, 162.4, 169.8 (pyrone-CO) ppm.
2-Amino-6-(azidomethyl)-4-(4-nitrophenyl)-8-oxo-4,8-dihydropy-
rano[3,2-b]pyran-3-carbonitrile (4d, C16H10N6O5) Orange
solid; yield 0.36 g (98%); m.p.: 193–195 °C; FT-IR (KBr):
ꢀ
m = 3398 and 3295 (–NH2), 3190, 2854, 2322, 2198 (–CN),
2101 (–N3), 1643 (pyrone-CO), 1597, 1424, 1349, 1216,
1013, 861, 628 cm-1
;
1H NMR (300 MHz, DMSO-d6):
2-Amino-6-(azidomethyl)-4-(3-hydroxyphenyl)-8-oxo-4,8-dihy-
dropyrano[3,2-b]pyran-3-carbonitrile (4h, C16H11N5O4) Yel-
low solid; yield 0.31 g (92%); m.p.: 209–211 °C; FT-IR
d = 4.22–4.37 (dd, 2H, –CH2N3), 5.11 (s, 1H, –CH-chiral),
6.49 (s, 1H, pyrone-H), 7.37 (s, 2H, NH2), 7.62–7.65 (d,
J = 8.7 Hz, 2H, H-Ph), 8.24–8.27 (d, J = 8.7 Hz, 2H,
H-Ph) ppm; 13C NMR (75 MHz, DMSO-d6): d = 50.1 (C-
chiral), 55.1 (–CH2N3), 114.7, 119.3, 123.5, 125.5, 129.9,
131.2, 137.3, 147.6, 159.7, 162.6, 169.8 (pyrone-CO) ppm.
ꢀ
(KBr): m = 3372 (–NH2), 3211, 2858, 2313, 2192 (–CN),
2105 (–N3), 1638 (pyrone-CO), 1589, 1425, 1358, 1276,
1
1215, 1020, 860, 627 cm-1; H NMR (300 MHz, DMSO-
d6): d = 4.26–4.39 (dd, 2H, –CH2N3), 4.69 (s, 1H, –CH-
chiral), 6.47 (s, 1H, pyrone-H), 6.66–6.71 (m, 3H, H-Ph),
7.14–7.19 (m, 1H, H-Ph), 7.25 (s, 2H, NH2), 9.51 (s, 1H,
OH) ppm; 13C NMR (75 MHz, DMSO-d6): d = 50.1 (C-
chiral), 56.1 (–CH2N3), 114.7, 119.6, 129.4, 131.2, 136.8,
142.47, 150.3, 158.2, 159.6, 162.5, 169.8 (pyrone-CO)
ppm; MS: m/z (%) = 337 (M?, 100), 272 (35), 244 (91),
216 (40).
2-Amino-6-(azidomethyl)-8-oxo-4-(3,4,5-trimethoxyphenyl)-4,8-
dihydropyrano[3,2-b]pyran-3-carbonitrile (4e, C19H17N5O6)-
Cream solid; yield 0.37 g (90%); m.p.: 202–204 °C; FT-IR
ꢀ
(KBr): m = 3398 and 3319 (–NH2), 3185, 2943, 2842,
2314, 2195 (–CN), 2109 (–N3), 1645 (pyrone-CO), 1598,
1
1428, 1331, 1216, 1127, 1012, 863, 684 cm-1; H NMR
(300 MHz, DMSO-d6): d = 3.64 (s, 3H, –OMe), 3.75 (s,
6H, –OMe), 4.28–4.39 (dd, 2H, –CH2N3), 4.79 (s, 1H, –
CH-chiral), 6.46 (s, 1H, pyrone-H), 6.56 (s, 2H, NH2), 7.22
(s, 2H, H-Ph) ppm; 13C NMR (75 MHz, DMSO-d6):
d = 50.2 (C-chiral), 55.8 (–CH2N3), 56.8 (–OCH3), 105.5,
114.5, 119.7, 136.3, 149.7, 153.6, 159.6, 162.4, 169.9
(pyrone-CO) ppm; MS: m/z (%) = 411 (M?, 100), 346
(25), 216 (54).
2-Amino-6-(azidomethyl)-4-(2-nitrophenyl)-8-oxo-4,8-dihydropy-
rano[3,2-b]pyran-3-carbonitrile (4i, C16H10N6O5) Orange solid;
yield 0.36 g (98%); m.p.: 194–196 °C; FT-IR (KBr):
ꢀ
m = 3400 and 3318 (–NH2), 3198, 3069, 2929, 2376, 2194
(–CN), 2118 (–N3), 1649 (pyrone-CO), 1520, 1431, 1358,
1
1209, 1086, 1017, 864, 709 cm-1; H NMR (300 MHz,
DMSO-d6): d = 4.17–4.33 (dd, 2H, –CH2N3), 5.51 (s, 1H,
–CH-chiral), 6.48 (s, 1H, pyrone-H), 6.66–6.71 (m, 3H,
H-Ph), 7.39 (s, 2H, NH2), 7.57–7.62 (m, 2H, H-Ph),
7.74–7.79 (m, 1H, H-Ph), 7.96–7.98 (m, 1H, H-Ph) ppm;
2-Amino-6-(azidomethyl)-4-(2-methoxyphenyl)-8-oxo-4,8-dihy-
dropyrano[3,2-b]pyran-3-carbonitrile (4f, C17H13N5O4) Brown
solid; yield 0.34 g (96%); m.p.: 197–199 °C; FT-IR (KBr):
123

K. O. Aghbash et al.
13C NMR (75 MHz, DMSO-d6): d = 49.5 (C-chiral), 54.3
(–CH2N3), 114.8, 119.1, 128.7, 131.4, 137.3, 148.6, 149.6,
159.9, 162.5, 169.8 (pyrone-CO) ppm.
˚
radiation (k = 0.71073 A). Data collection: X-AREA 1.31
[63], cell refinement: X-AREA [63], data reduction:
X-AREA [63], program(s) used to solve structure:
SHELXS97 [64], program(s) applied to refine the synthetic
compound structure: SHELXL97 [64], molecular graphics:
ORTEP-3 for Windows and software applied to prepare
material for publication: WinGX. Crystallographic data
were deposited in the CCDC 1823236 registration number.
These information could be earned free of charge from The
Cambridge Crystallographic Data Center via request to
CCDC, 12 Union Road, Cambridge, UK or www.ccdc.
2-Amino-6-(azidomethyl)-4-(5-bromo-2-hydroxyphenyl)-8-
oxo-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile
(4j,
C16H10BrN5O4) Brown solid; yield 0.38 g (91%); m.p.:
ꢀ
205–207 °C; FT-IR (KBr): m = 3430 and 3326 (–NH2),
3240, 3071, 2308, 2191(–CN), 2103 (–N3), 1650 (pyrone-
CO), 1410, 1228, 1030, 983, 879, 675 cm-1 1H NMR
;
(300 MHz, DMSO-d6): d = 4.23–4.34 (dd, 2H, –CH2N3),
5.25 (s, 1H, –CH-chiral), 6.41 (s, 1H, pyrone-H), 7.02–7.04
(m, 1H, H-Ph), 7.17 (s, 2H, NH2), 7.25 (s, 1H, H-Ph),
7.45–7.48 (m, 1H, H-Ph), 9.30 (s, 1H, OH) ppm; 13C NMR
(75 MHz, DMSO-d6): d = 50.0 (C-chiral), 55.0 (–CH2N3),
112.7, 116.6, 120.0, 122.1, 130.8, 131.7, 142.2, 148.9,
151.1, 161.9, 174.0 (pyrone-CO) ppm; MS: m/z (%) = 417
(M??1, 26), 416 (M?, 16), 373 (73), 289 (21), 249 (100),
223 (43), 167 (44), 143 (33), 114 (64), 69 (33).
cam.ac.uk/data_request/cif
(fax:
?44-1223-336033,
e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgements We thank the Urmia University Research
Council for supporting this work.
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solid; yield 0.33 g (97%); m.p.: 195–197 °C; FT-IR (KBr):
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123