One-pot synthesis of 2-aminotetrahydrothiopyrano[4,3-b]-pyran-3- carbonitrile derivatives using mesoporous NH2-MCM-41

Article abstract of DOI:10.1007/s00706-013-1035-2

A facile and general procedure is presented for the one-pot synthesis of 2-aminotetrahydrothiopyrano[4,3-b]pyran-3-carbonitrile derivatives. It is based on the threecomponent condensation of aliphatic, aromatic, or heterocyclic aldehydes, malononitrile, and thiopyran in the presence of mesoporous amino-functionalized MCM-41 silica in ethanol. This efficient technique has the advantage of giving 2-aminotetrahydrothiopyrano[4,3-b]pyran-3-carbonitrile derivatives using a heterogeneous mesoporous reagent in high yields, in short reaction times, and offers a simple product isolation procedure. Springer-Verlag Wien 2013.

Full text of DOI:10.1007/s00706-013-1035-2

Monatsh Chem
DOI 10.1007/s00706-013-1035-2
ORIGINAL PAPER
One-pot synthesis of 2-aminotetrahydrothiopyrano[4,3-b]-
pyran-3-carbonitrile derivatives using mesoporous
NH2-MCM-41
•
Maryam Mirza-Aghayan Farhad Saravani
•
•
•
Ali Akbar Tarlani Mohammad Saeed Abaee
Rabah Boukherroub
Received: 4 December 2012 / Accepted: 9 June 2013
Ó Springer-Verlag Wien 2013
Abstract A facile and general procedure is presented for
the one-pot synthesis of 2-aminotetrahydrothiopyrano[4,3-
b]pyran-3-carbonitrile derivatives. It is based on the three-
component condensation of aliphatic, aromatic, or hetero-
cyclic aldehydes, malononitrile, and thiopyran in the
presence of mesoporous amino-functionalized MCM-41
silica in ethanol. This efficient technique has the advantage
of giving 2-aminotetrahydrothiopyrano[4,3-b]pyran-3-car-
bonitrile derivatives using a heterogeneous mesoporous
reagent in high yields, in short reaction times, and offers a
simple product isolation procedure.
derivatives are generally synthesized using a three-compo-
nent reaction of cyclic 1,3-diketones, aryl aldehydes, and
malononitrile under various reaction conditions. The con-
ventional reported syntheses of 4H-chromene derivatives
employ piperidine and triethylamine as catalytic or stoichi-
ometric reagents in organic solvents [2–5]. In recent years,
interest in this reaction has increased rapidly and several
modified procedures have been reported [6–8]. Alternative
and more efficient strategies for the synthesis of 4H-chro-
mene derivatives involving different catalysts and conditions
including alkylammonium salts [9, 10], (NH4)2HPO4 [11],
(S)-proline [12], Re(PFO)3 [13], and KF-Al2O3 [14] have
been described. Moreover, in view of the diverse therapeutic
activity, this reaction was enlarged by the variation of the
aldehyde, malononitrile derivatives [15], 1,3-dicarbonyl
compound building blocks, including the use of cyclic
ketones [16] and cyclic diketones [9, 17], and the use of 1- or
2-naphthol [18, 19] instead of ketones or diketones.
Keywords 2-Aminotetrahydrothiopyrano[4,3-b]-
pyran-3-carbonitrile Á Thiopyran Á Amino-functionalized
MCM-41 Á One-pot synthesis
Introduction
This work reports an efficient protocol for the synthesis
of 4H-chromene derivatives using heterocyclic ketones
instead of conventional ketones in the presence of meso-
porous NH2-MCM-41 silica. This is mainly motivated by
recent reports highlighting the design of sulfur-containing
drugs with interesting activities [20–23].
4H-Chromene derivatives are important heterocyclic com-
pounds with a number of biological and pharmacological
properties including spasmolytic, diuretic, anticoagulant,
anticancer, and antianaphylactic activities [1]. 4H-Chromene
It should be noted that using heterocyclic ketones
for the synthesis of 4H-chromene derivatives has been
reported only in a few examples [24]. Nakib et al.
[24] synthesized 2-amino-4-aryl-4H,5H-[1]benzothiopyr-
ano[4,3-b]pyran-3-carbonitriles by the reaction of
3-benzylidenethiochroman-4-one with malononitrile in the
presence of piperidine in moderate yields. These deriva-
tives displayed antifungal activity in vitro against the
pathogenic fungi Cryptococcus neoformans, Torulopsis
glabrata, Trichosporon cutaneum, Candida albicans,
C. paropsilosis, and C. tropicalis.
M. Mirza-Aghayan (&) Á F. Saravani Á A. A. Tarlani Á
M. S. Abaee
Chemistry and Chemical Engineering Research Center of Iran
(CCERCI), P.O. Box 14335-186, Tehran, Iran
e-mail: m.mirzaaghayan@ccerci.ac.ir
R. Boukherroub
Institut de Recherche Interdisciplinaire (IRI, USR 3078),
Parc de la Haute Borne, 50 avenue de Halley, BP 70478,
59658 Villeneuve d’Ascq, France
123

M. Mirza-Aghayan et al.
Results and discussion
Table 1 Different conditions for the synthesis of 2-amino-4-(4-
nitrophenyl)-7,8-dihydro-4H,5H-thiopyrano[4,3-b]pyran-3-carboni-
trile (4e)
In the framework of our studies on multicomponent reactions
for the synthesis of 2-amino-5,6-dihydropyrimidin-4(3H)-
one, 2-aminotetrahydro-4H-chromene, and 2-amino-4H-
benzo[h]chromene derivatives using amino-functionalized
MCM-41 as catalyst [25, 26] and in continuation of our
interest in the application of mesoporous MCM-41, we
report herein an efficient protocol for the synthesis of
2-aminothiopyran derivatives using heterocyclic ketones
instead of conventional ketones. One-pot condensation of
various aldehydes 1a–1k with malononitrile (2) and thio-
pyran (3) in the presence of mesoporous amino-
functionalized MCM-41 (NH2-MCM-41) in refluxing etha-
nol was investigated for the synthesis of novel
2-aminotetrahydrothiopyrano[4,3-b]pyran-3-carbonitrile
derivatives (Scheme 1).
Entry
Catalyst/mol%
Time/h
Yield/%a
1
2
3
4
5
6
7
0
24
24
24
8
0
AlPW12O40ÁXH2O (3)
AlPW12O40ÁXH2O (6)
NH2-MCM-41 (10)
NH2-MCM-41 (20)
NH2-MCM-41 (40)
NH2-MCM-41 (100)
0
0
53
60
85
87
5
2.5
2.5
Reaction conditions: 4-nitrobenzaldehyde (1 mmol), malononitrile
(1 mmol), and thiopyran (1 mmol) in refluxing ethanol
a
Isolated yield
Table 2 Synthesis of 2-amino-4-aryl-7,8-dihydro-4H,5H-thiopyr-
ano[4,3-b]pyran-3-carbonitrile building blocks 4a–4k
Mesoporous MCM-41 silica utilized in this work was
synthesized according to a previously reported procedure
and functionalized with 3-aminopropyltriethoxysilane
(APTES) [27–29]. Elemental analyses supported that the
amine was immobilized on the surface. Brunauer–Emmett–
Teller (BET) surface area measurement revealed that the
MCM-41 surface area (1,018 m2/g) decreased to 638 m2/g
after grafting APTES molecules. The amount of grafted
amine on MCM-41 is estimated to be 3.24 mmol of amine
per gram of silica [30].
Entry
R
Product Time/h Yield/%a M.p./°C
1
C6H5
4a
4b
4c
4d
4e
4f
8
70
75
79
65
85
97
55
90
90
80
60
254.3
231.3
235.2
237
2
p-CH3-C6H4
p-OH-C6H4
m-OH-C6H4
p-NO2-C6H4
m-NO2-C6H4
o-NO2-C6H4
p-Cl-C6H4
p-Br-C6H4
5
3
5.45
8
4
5
2.30
4.30
8
229.2
237.2
220.5
254.4
257.2
245
6
7
4g
4h
4i
The model reaction was carried out simply by mixing an
equimolar quantity of p-nitrobenzaldehyde (1e), malono-
nitrile, and thiopyran in ethanol. The resulting mixture was
heated to reflux for the time indicated in Table 1. The
progress of the reaction was monitored by TLC. Then the
mixture was poured into hot ethanol and filtered through a
sintered funnel. The filtrate was evaporated in vacuo. The
crude product was purified by recrystallization in ethanol.
When the reaction was carried out in refluxing ethanol as
solvent in catalyst-free conditions, the reaction was rela-
tively slow and no product was formed after 24 h (Table 1,
entry 1). Increasing the reaction time did not show a sig-
nificant effect on the yield.
8
7
9
3.30
2
10
11
p-CH3O-C6H4 4j
2-Furanyl 4k
8
223.4
Reaction conditions: aldehyde (1 mmol), malononitrile (1.1 mmol),
thiopyran (1 mmol), NH2-MCM-41 (40 mol%) in refluxing ethanol
a
Isolated yield
When the reaction was carried out in the presence of
mesoporous NH2-MCM-41 (10 mol%), the product 4e was
isolated in 53 % yield after 8 h in refluxing ethanol
(Table 1, entry 4). The results suggest that amino-func-
tionalized MCM-41 in ethanol can be used as an efficient
and alternative reagent for this reaction. The results are
summarized in Table 1.
We then examined the influence of AlPW12O40ÁXH2O
heteropolyacid (3 mol%) catalyst on this reaction (Table 1,
entry 2). The catalyst was found to be inefficient for this
reaction and no product was formed after 24 h in refluxing
ethanol even with 6 mol% of catalyst (Table 1, entry 3).
The influence of the NH2-MCM-41 concentration on the
reaction yield was investigated. 2-Amino-4-(4-nitro-
phenyl)-7,8-dihydro-4H,5H-thiopyrano[4,3-b]pyran-3-car-
bonitrile (4e) was obtained in 60, 85, and 87 % yield by
increasing NH2-MCM-41 concentration to 20, 40, and
100 mol%, respectively (Table 1, entries 5–7). Increasing
the NH2-MCM-41 concentration over 40 mol% shows no
significant effect on the yield, suggesting that 40 mol% of
NH2-MCM-41 is sufficient for this reaction.
Scheme 1
Ar
O
CN
-
-
NH2 MCM 41
S
ArCHO
NC
CN
EtOH reflux
,
NH2
S
O
1a-1k
2
3
4a-4k
We tested a variety of aldehydes 1a–1k under the opti-
mized reaction conditions. It should be noted that for an
123

One-pot synthesis
easy purification (facile elimination of the unreacted alde-
hyde), we used 1.1 equivalents of malononitrile for
1 equivalent of aldehyde. The results in Table 2 show that
NH2-MCM-41 can be used in the synthesis of 2-amino-4-
aryl-7,8-dihydro-4H,5H-thiopyrano[4,3-b]pyran-3-carboni-
trile building blocks 4a–4k with various aromatic and
heterocyclic aldehydes in high yields and short reaction
times. The presence of electron-donating, electron-with-
drawing, and heterocyclic groups on the aldehyde afforded
the corresponding products in good to excellent yields. All
compounds were characterized on the basis of their spec-
troscopic data such as 1H and 13C NMR, mass spectroscopy,
infrared spectra, and elemental analysis.
which are often encountered in biologically active com-
pounds. Formation of products using amino-functionalized
MCM-41 as a highly promising environmentally friendly
base reagent, in good to high yields within relatively short
time periods, and ease of operation and purification make
this protocol attractive. Reusability of amino-functional-
ized MCM-41 is an additional advantage. The reaction
system can be successfully applied to a variety of aryl and
heterocyclic aldehydes to synthesize a wide variety of
novel heterocycles in good to high yields. Further inves-
tigations are needed to estimate the biological activity of
these novel 2-aminothiopyran derivatives.
We also investigated the reusability of the NH2-MCM-
41. After completion of the reaction, hot ethanol was added
to the reaction mixture while stirring and the mixture was
filtered through a sintered funnel to separate the insoluble
catalyst. Then the mesoporous NH2-MCM-41 was dried
and re-used in another reaction. The recycled NH2-MCM-
41 was used for three consecutive reactions without any
significant loss in its activity and the product 4e was
obtained in 85, 84, and 82 % yield, respectively.
Experimental
Melting points were determined in evacuated capillaries
with a Bu¨chi B-545 apparatus. 1H NMR spectra were
recorded on Bruker spectrometer at 80 or 500 MHz in
DMSO-d6 using tetramethylsilane as internal standard. 13
C
NMR spectra were recorded at 100 or 125 MHz in DMSO-
d6. Mass spectra were obtained on a Fisons GC 8000/TRIO
1000 at 70 eV. Infrared (IR) spectra were recorded from
KBr disks with a Bruker Vector 22 Fourier transform
infrared (FTIR) spectrophotometer. Elemental analyses
were performed on a ThermoFinigan Flash EA 1112 series
elemental analyzer.
A reasonable mechanism for this reaction is outlined in
Scheme 2 [9]. The reaction may proceed through the ary-
lidenemalononitrile intermediate (formed in situ by
the reaction of an aldehyde with malononitrile), and the
subsequent addition of enolate of thiopyran to the arylid-
enemalononitrile to generate the intermediate I. The
cyclization of the intermediate I followed by tautomeriza-
tion affords the corresponding 2-amino-4-aryl-7,8-dihydro-
Synthesis of amino-functionalized MCM-41
(NH2-MCM-41)
4H,5H-thiopyrano[4,3-b]pyran-3-carbonitrile
building
blocks 4a–4k (Scheme 2). It should be noted that the pres-
ence of arylidenemalononitrile intermediate is made based
on GCMS analysis. Furthermore, we obtained the same final
product by performing the reaction in two steps: the first step
consists in the synthesis of arylidenemalononitrile by the
reaction of an aldehyde with malononitrile, and the second
step is the reaction of the arylidenemalononitrile with
thiopyran.
In a typical reaction, 1 g of MCM-41 was suspended in
50 cm3 of toluene and the mixture was stirred for 1 h. To
this mixture, 1.5 g of APTES was added and refluxed
overnight. The white solid was filtered through a sintered
funnel and was extracted using a Soxhlet extractor with
toluene and dried overnight under reduced pressure at
70 °C [30].
In conclusion, we have developed an efficient procedure
for the synthesis of 2-amino-4-aryl-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile building blocks,
Typical procedure for the synthesis
of 2-aminothiopyran derivatives
A solution of aldehyde 1a–1k (1 mmol), malononitrile (2,
1.1 mmol), and thiopyran (3, 1 mmol) in 2 cm3 of ethanol
was stirred mechanically in the presence of 40 mol% of
mesoporous amino-functionalized MCM-41. The reaction
mixture was refluxed for the time indicated in Table 2 and the
progress of the reaction was monitored by TLC. Then the
mixture was poured into hot ethanol and stirred for 30 min.
The mixture was filtered through a sintered funnel and the
solvent was evaporated in vacuo. For further purification the
crude product was recrystallized from ethanol.
Scheme 2
Ar
H
CN
CN
O
S
ArCHO
NC
CN
-
H2O
Ar
Ar
Ar
O
H
H
CN
NH
CN
CN
Tautomerization
Cyclization
S
S
S
O
NH2
O
N
4
I
123

M. Mirza-Aghayan et al.
2-Amino-4-phenyl-7,8-dihydro-4H,5H-thiopyrano[4,3-b]-
pyran-3-carbonitrile (4a, C15H14N2OS)
100 MHz): d = 25.47, 28.01, 35.98, 43.14, 49.77, 81.89,
112.43, 112.83, 116.45, 117.86, 130.07, 130.43, 135.72,
144.78, 158.08 ppm; MS (EI, 70 eV): m/z (%) = 287 (3,
[M ? 1]?), 261 (5), 244 (1), 195 (6), 75 (45), 45 (46), 31
(100); IR (KBr): vꢀ = 4,313, 3,330, 3,225, 2,872, 2,212,
1,649, 1,588, 1,492, 1,456, 1,418, 1,386, 1,341, 1,315,
M.p.: 254.3 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.21–
2.31 (m, 2H, CH2), 2.85–3.52 (m, 3H, CH2), 3.65 (d,
J = 14.4 Hz, 1H, CH2), 5.80–6.05 (m, 1H, CH), 7.48 (br s,
7H, NH2 and CH arom) ppm; 13C NMR (DMSO-d6,
100 MHz): d = 25.45, 28.15, 35.57, 43.30, 49.92, 81.95,
112.46, 112.73, 116.46, 118.03, 129.37, 129.73, 130.07,
134.30, 144.61 ppm; MS (EI, 70 eV): m/z (%) = 270 (5,
M?), 228 (5), 193 (6), 77 (7); IR (KBr): vꢀ = 3,424, 3,343,
3,254, 2,923, 2,210, 1,646, 1,600, 1,455, 1,421, 1,391,
1,283 cm-1; Anal. Calcd. for C15H14N2OS: C, 66.64; H,
5.22; N, 10.36 %. Found: C, 67.80; H, 5.30; N, 10.11 %.
1,283, 1,219, 1,165, 1,102 cm-1
; Anal. Calcd. for
C15H14N2O2S: C, 62.92; H, 4.93; N, 9.78 %. Found: C,
63.21; H, 4.95; N, 9.75 %.
2-Amino-4-(4-nitrophenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4e, C15H13N3O3S)
M.p.: 229.2 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.15–
2.40 (m, 2H, CH2), 2.88–3.70 (m, 3H, CH2), 3.95 (d,
J = 14.4 Hz, 1H, CH2), 5.90–6.05 (m, 1H, CH), 7.53 (br s,
2H, NH2), 7.82 (d, J = 8.4 Hz, 2H, CH arom), 8.33 (d,
J = 8.9 Hz, 2H, CH arom) ppm; 13C NMR (DMSO-d6,
100 MHz): d = 25.44, 27.96, 35.29, 42.65, 49.16, 82.05,
112.15, 112.36, 116.34, 118.47, 124.21, 129.60, 141.56,
144.14, 148.50 ppm; MS (EI, 70 eV): m/z (%) = 316 (3,
[M ? 1]?), 269 (3), 227 (3), 199 (70), 141 (100), 115 (78),
75 (80), 45 (83); IR (KBr): vꢀ = 3,451, 3,358, 2,881, 2,208,
1,635, 1,593, 1,530, 1,390, 1,348, 1,284, 1,110 cm-1; Anal.
Calcd. for C15H13N3O3S: C, 57.13; H, 4.16; N, 13.33 %.
Found: C, 58.26; H, 4.15; N, 13.30 %.
2-Amino-4-(4-methylphenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4b, C16H16N2OS)
1
M.p.: 231.1 °C; H NMR (DMSO-d6, 80 MHz): d = 2.15–
2.30 (m, 2H, CH2), 2.32 (s, 3H, CH3), 2.80–3.45(m, 3H, CH2),
3.58(d, J = 12.0 Hz, 1H, CH2), 5.80–6.00 (m, 1H, CH), 7.20–
7.40 (m, 4H, CH arom), 7.45 (br s, 2H, NH2) ppm; 13C NMR
(DMSO-d6, 100 MHz):d = 21.18,25.43, 28.14, 35.62, 43.41,
49.66, 81.92, 112.51, 112.81, 116.45, 117.94, 127.45, 129.95,
131.24, 139.18, 144.61 ppm; MS (EI, 70 eV): m/z (%) = 285
(1, [M ? 1]?), 242 (2), 115 (13), 91 (20), 75 (5), 45 (100); IR
(KBr): vꢀ = 3,555, 3,426, 3,332, 3,222, 2,969, 2,874, 2,210,
1,644, 1,600, 1,515, 1,418, 1,388, 1,315, 1,281, 1,046 cm-1
;
2-Amino-4-(3-nitrophenyl)-7,8-dihydro-4H,5H-
Anal. Calcd. for C16H16N2OS: C, 67.58; H, 5.67; N, 9.85 %.
Found: C, 67.99; H, 5.64; N, 9.81 %.
thiopyrano[4,3-b]pyran-3-carbonitrile
(4f, C15H13N3O3S)
M.p.: 237.2 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.10–
2.40 (m, 2H, CH2), 2.90–3.70 (m, 3H, CH2), 4.03 (d,
J = 13.6 Hz, 1H, CH2), 5.85–6.10 (m, 1H, CH), 7.55 (br s,
2H, NH2), 7.65–8.50 (m, 4H, CH arom) ppm; 13C NMR
(DMSO-d6, 100 MHz): d = 25.43, 28.01, 35.25, 42.90,
49.10, 82.10, 112.23, 112.41, 116.36, 118.51, 124.76,
129.56, 131.02, 136.92, 144.09 ppm; MS (EI, 70 eV): m/z
(%) = 316 (1, [M ? 1]?), 244 (3), 115 (2), 75 (3), 45 (85),
30 (100); IR (KBr): vꢀ = 3,331, 3,152, 2,201, 1,651, 1,536,
2-Amino-4-(4-hydroxyphenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4c, C15H14N2O2S)
1
M.p.: 235.2 °C; H NMR (DMSO-d6, 80 MHz): d = 2.10–
2.40 (m, 2H, CH2), 2.60–3.35 (m, 3H, CH2), 3.49 (d,
J = 14.4 Hz, 1H, CH2), 5.85–6.10 (m, 1H, CH), 6.79 (d,
J = 8.8 Hz, 2H, CH arom), 7.27 (d, J = 7.8 Hz, 2H, CH
arom), 7.42 (br s, 2H, NH2), 9.64 (s, 1H, OH) ppm; 13C NMR
(DMSO-d6, 100 MHz):d = 25.48,28.22, 35.80, 43.69, 49.61,
81.96, 112.64, 112.84, 116.10, 116.50, 117.85, 124.21, 130.26,
144.67, 158.50 ppm; MS (EI, 70 eV): m/z (%) = 287 (1,
[M ? 1]?), 261 (4), 244 (1), 115 (1), 75 (2), 29 (100); IR
(KBr): vꢀ = 3,514, 3,419, 3,336, 3,231, 2,874, 2,209, 1,654,
1,613, 1,598, 1,516, 1,446, 1,417, 1,387, 1,342, 1,263, 1,213,
1,198, 1,177 cm-1; Anal. Calcd. for C15H14N2O2S: C, 62.92;
H, 4.93; N, 9.78 %. Found: C, 63.37; H, 4.96; N, 9.63 %.
1,602, 1,417, 1,353, 1,047 cm-1
; Anal. Calcd. for
C15H13N3O3S: C, 57.13; H, 4.16; N, 13.33 %. Found: C,
58.62; H, 4.26; N, 13.04 %.
2-Amino-4-(2-nitrophenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4g, C15H13N3O3S)
M.p.: 220.5 °C; 1H NMR (DMSO-d6, 500 MHz):
d = 2.30–2.50 (m, 2H, CH2), 3.12–3.25 (m, 2H, CH2),
3.50 (d, J = 12.0 Hz, 1H, CH2), 4.16 (d, J = 12.0 Hz, 1H,
CH2), 5.99 (br s, 1H, CH), 7.58 (br s, 2H, NH2), 7.76 (t,
J = 8.0 Hz, 1H, CH arom), 7.92 (t, J = 8.0 Hz, 1H, CH
arom), 8.05–8.11 (m, 2H, CH arom) ppm; 13C NMR
(DMSO-d6, 125 MHz): d = 25.44, 28.01, 35.27, 42.90,
49.10, 82.09, 112.26, 112.43, 116.40, 117.61, 125.77,
2-Amino-4-(3-hydroxyphenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4d, C15H14N2O2S)
M.p.: 237.0 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.20–
2.40 (m, 2H, CH2), 2.90–3.70 (m, 4H, CH2), 5.80–6.00 (m,
1H, CH), 6.70–7.40 (m, 5H, CH arom), 7.45 (br s, 2H,
NH2), 9.62 (s, 1H, OH) ppm; 13C NMR (DMSO-d6,
123

One-pot synthesis
129.40, 131.00, 136.95, 144.05 ppm; MS (EI, 70 eV): m/z
(%) = 316 (8, [M ? 1]?), 244 (5), 115 (2), 76 (8), 45 (85),
30 (98); IR (KBr): vꢀ = 3,447, 3,320, 3,218, 2,967, 2,212,
2-Amino-4-(furan-2-yl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4k, C13H12N2O2S)
1,642, 1,599, 1,525, 1,344 cm-1
;
Anal. Calcd. for
M.p.: 231.1 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.00–
2.40 (m, 2H, CH2), 2.60–3.65 (m, 3H, CH2), 3.97 (d,
J = 12.0 Hz, 1H, CH2), 5.80–6.00 (m, 1H, CH), 6.50–6.70
(m, 2H, CH arom), 7.50 (br s, 2H, NH2), 7.83 (br s, 1H, CH
arom) ppm; 13C NMR (DMSO-d6, 100 MHz): d = 25.38,
27.58, 35.86, 41.59, 44.86, 81.82, 111.32, 112.51, 112.58,
117.82, 129.49, 145.16, 147.94 ppm; MS (EI, 70 eV): m/z
(%) = 235 (1), 193 (2), 115 (2), 45 (100); IR (KBr):
vꢀ = 3,424, 3,340, 3,222, 2,211, 1,644, 1,602, 1,497, 1,424,
1,391, 1,148, 1,016 cm-1; Anal. Calcd. for C13H12N2O2S:
C, 59.98; H, 4.65; N, 10.76 %. Found: C, 58.78; H, 4.67;
N, 10.65 %.
C15H13N3O3S: C, 57.13; H, 4.16; N, 13.33 %. Found: C,
58.43; H, 4.09; N, 13.12 %.
2-Amino-4-(4-chlorophenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4h, C15H13ClN2OS)
M.p.: 231.1 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.15–
2.40 (m, 2H, CH2), 2.91–3.60 (m, 3H, CH2), 3.73 (d,
J = 13.6 Hz, 1H, CH2), 5.85–6.05 (m, 1H, CH), 7.30–7.70
(m, 6H, NH2 and CH arom) ppm; 13C NMR (DMSO-d6,
100 MHz): d = 25.43, 28.09, 35.43, 43.13, 49.18, 82.05,
112.37, 112.58, 116.39, 118.22, 129.45, 129.90, 133.29,
134.57, 144.38 ppm; MS (EI, 70 eV): m/z (%) = 305 (3,
[M ? 1]?), 278 (1), 244 (5), 115 (30), 75 (45), 45 (100); IR
(KBr): vꢀ = 3,432, 3,345, 3,212, 2,210, 1,640, 1,598, 1,494,
1,413, 1,387, 1,342, 1,278, 1,227, 1,094, 1,047,
1,016 cm-1; Anal. Calcd. for C15H13ClN2OS: C, 59.11;
H, 4.30; N, 11.63 %. Found: C, 60.75; H, 4.36; N, 11.32 %.
References
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2-Amino-4-(4-bromophenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
(4i, C15H13BrN2OS)
M.p.: 257.2 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.10–
2.35 (m, 2H, CH2), 2.90–3.55 (m, 3H, CH2), 3.76 (d,
J = 14.4 Hz, 1H, CH2), 5.85–6.00 (m, 1H, CH), 7.35–7.80
(m, 6H, NH2 and CH arom) ppm; 13C NMR (DMSO-d6,
100 MHz): d = 25.48, 28.12, 35.35, 43.05, 49.30, 82.05,
112.37, 112.55, 116.42, 118.23, 123.29, 129.87, 132.37,
133.65, 144.33 ppm; MS (EI, 70 eV): m/z (%) = 351 (2,
[M ? 2]?), 349 (2) (M)?, 227 (13), 125 (15), 75 (6), 45
(100); IR (KBr): vꢀ = 3,434, 3,345, 3,212, 2,209, 1,640,
1,597, 1,489, 1,411, 1,389, 1,278, 1,227, 1,076,
1,011 cm-1; Anal. Calcd. for C15H13BrN2OS: C, 51.59;
H, 3.75; N, 8.02 %. Found: C, 52.34; H, 3.73; N, 8.35 %.
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2-Amino-4-(4-methoxyphenyl)-7,8-dihydro-4H,5H-
thiopyrano[4,3-b]pyran-3-carbonitrile
15. Ghorbani-Vaghei R, Toghraei-Semiromi Z, Karimi-Nami R
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16. Jin TS, Zhao R-Q, Li T-S (2006) Arkivoc xi:176
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(4j, C16H16N2O2S)
M.p.: 245.0 °C; 1H NMR (DMSO-d6, 80 MHz): d = 2.10–
2.42 (m, 2H, CH2), 2.72–3.47 (m, 3H, CH2), 3.60 (d,
J = 14.4 Hz, 1H, CH2), 3.76 (s, 3H, OCH3), 5.83–6.10 (m,
1H, CH), 7.00–7.45 (m, 4H, CH arom and 2H, NH2) ppm;
13C NMR (DMSO-d6, 100 MHz): d = 25.45, 28.19, 35.74,
43.58, 49.37, 55.60, 81.91, 112.60, 112.82, 114.18, 116.49,
117.89, 125.99, 130.19, 144.65, 160.18 ppm; MS (EI,
70 eV): m/z (%) = 301 (1, [M ? 1]?), 244 (1), 227 (4), 115
(5), 45 (100); IR (KBr): vꢀ = 3,429, 3,344, 3,244, 2,213,
1,641, 1,612, 1,596, 1,516, 1,420, 1,388, 1,289, 1,183,
1,027 cm-1; Anal. Calcd. for C16H16N2O2S: C, 63.98; H,
5.37; N, 9.33 %. Found: C, 65.01; H, 5.37; N, 9.56 %.
123

M. Mirza-Aghayan et al.
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