Ultrasound mediated synthesis of dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile derivatives in H2O/EtOH medium

Article abstract of DOI:10.1515/hc-2017-0014

A one-pot cyclocondensation of 1,3-dioxane-5-one (1) with malononitrile and aromatic aldehydes in aqueous sodium hydroxide under ultrasonic irradiation furnishes a series of pyrano[3,2-d][1,3]dioxin derivatives 3. Reactions are completed after a few minutes and the precipitated products are purified by simple crystallization from ethanol. The reaction with ethyl cyanoacetate instead of malononitrile gives the respective analogous products in high yields.

Full text of DOI:10.1515/hc-2017-0014

Heterocycl. Commun. 2017; 23(2): 91–95
Mohammad M. Mojtahedi*, Masoomeh Mehraban, Kiana Darvishi and M. Saeed Abaee
Ultrasound mediated synthesis of dihydropyrano-
[3,2-d][1,3]dioxin-7-carbonitrile derivatives
in H2O/EtOH medium
DOI 10.1515/hc-2017-0014
Received January 25, 2017; accepted March 7, 2017
as bidentate iron(III) chelators with potential for oral
administration [20].
In the framework of our studies on aldol condensa-
tion reactions [21, 22], we have reported the synthesis of
bisarylmethylidene derivatives of various six-membered
homocyclic and heterocyclic ketones [23, 24]. Meanwhile,
substituted 2,2-dimethyl-1,3-dioxan-5-ones 2 can serve as
a synthon for dihydroxyacetone derivatives [25, 26]. In
addition, these specific bisarylmethylidene compounds
have the potential to be converted to a vicinal 1,2,3-tricar-
bonyl skeleton, a motif which is found in the structure of
several natural products [27]. On this track, we decided to
Abstract: A one-pot cyclocondensation of 1,3-dioxane-
5-one (1) with malononitrile and aromatic aldehydes in
aqueous sodium hydroxide under ultrasonic irradiation
furnishes a series of pyrano[3,2-d][1,3]dioxin derivatives
3. Reactions are completed after a few minutes and the
precipitated products are purified by simple crystalliza-
tion from ethanol. The reaction with ethyl cyanoacetate
instead of malononitrile gives the respective analogous
products in high yields.
Keywords: aqueous; 1,3-dioxane-5-one; multicomponent take advantage of the functionality of products 2 by sub-
reaction; one-pot synthesis; ultrasonication.
jecting them to the reaction with malononitrile to access
products 3.
Introduction
Results and discussion
The pyrano[3,2-d][1,3]dioxin bicyclic skeleton is a key
motif in many naturally occurring compounds [1] and bio-
logically active and medicinally important carbohydrates
[2–4]. Some important examples include antifungal theo-
pederins marine sponge [5], mycalamides with antiviral
and antitumor properties [6], lolitrem B as an inhibitor of
human large conductance calcium-activated potassium
channels [7], sialosides with bacterial sialidases activ-
ity [8] and diphenylpyrazoles as breast cancer inhibitors
[9]. In addition, the pyranodioxane moieties are useful
intermediates in the synthesis of natural products and
other important compounds [10–15]. Examples include
(ꢀ+)-papulacandin D [16], substituted D-glucals [17],
(–)-isatisine A [18], hydroxypyridin-4-ones as antimalar-
ial agents [19] and hydroxyalkyl-3-hydroxypyridin-4-ones
A one-pot ultrasound-mediated reaction of compound 1
with two equivalents of an aromatic aldehyde generates
in situ product 2 that undergoes a subsequent cyclocon-
densation with malononitrile to produce a dihydropyrano-
[3,2-d][1,3]dioxin-7-carbonitrile 3 in high yield (Scheme 1).
It should be noted that the synthesis of analogous com-
pounds [28, 29] have been only reported using a stepwise
procedure. To the best of our knowledge, the only avail-
able one-pot method in the literature is the recent work we
published for the thiopyran based structures [30].
We first optimized the reaction conditions by studying
the condensation of 2,2-dimethyl-1,3-dioxan-5-one (1) with
benzaldehyde and malononitrile. Treatment of 1 with an
aqueous solution of NaOH (25%) and two equivalents of
benzaldehyde in EtOH resulted in complete conversion of
the reactants to 2a after 2 min of ultrasonic irradiation, as
indicated by TLC analysis. When malononitrile was added
to the reaction mixture and sonication was continued for
another 2 min, product 3a (94%) precipitated rapidly. To
evaluate the role of ultrasonication in the process, the
same treatment was repeated under silent and reflux con-
ditions. In these two cases, much lower yields of 3a (10%
and 40%) were obtained after 24 h and 8 h, respectively.
*Corresponding author: Mohammad M. Mojtahedi, Organic
Chemistry Department, Chemistry and Chemical Engineering
Research Center of Iran, P.O. Box 14335-186, Tehran, Iran,
e-mail: mojtahedi@ccerci.ac.ir
Masoomeh Mehraban, Kiana Darvishi and M. Saeed Abaee: Organic
Chemistry Department, Chemistry and Chemical Engineering
Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
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ꢀM.M. Mojtahedi et al.: Synthesis of dihydropyranodioxin-7-carbonitriles
NH2
CN
a: Ar = Ph
b: Ar = 2-ClC6H4
c: Ar = 4-ClC6H4
d: Ar = 2,4-Cl2C6H3
e: Ar = 3,4,5-(MeO)3C6H2
f: Ar = 4-MeC6H4
g: Ar = 2-MeOC6H4
h: Ar = 4-MeOC6H4
i: Ar = 2-thienyl
O
O
O
NC
CN
Ar CHO, NaOH
EtOH, H2O, ))))
Ar
Ar
Ar
Ar
O
O
O
O
O
O
))))
1
2a–i
3a–i
Scheme 1ꢁ
NH2
The use of other inorganic bases including Ca(OH)2, LiOH,
KOH and K2CO3 resulted in a decreased efficiency of the
reaction. Similarly, replacement of NaOH with organic
bases such as Et2NH, Et3N, morpholine and pyrrolidine
lowered the yield of 3a. Further optimization experiments
showed that ethanol is the optimum medium and other
solvents including MeCN, EtOAc and water are not as effi-
cient as ethanol, giving 21%–65% of the desired product.
Variation of the quantity of the base showed that the
optimum concentration of NaOH is 25%.
CO2Et
X
O
O
CN
NaOH, EtOH
O
O
O
O
))))
CO2Et
X
X
CHO
1
3j: X = Cl (30 min, 90%)
3k: X = Me (36 min, 89%)
Scheme 2ꢁ
O
O
O
Ar
Ar
O
O
Ar
Ar
Ar
The optimized conditions were used to evaluate the
generality of the process. In addition to benzaldehyde,
the use of other aromatic aldehydes bearing electron
withdrawing or electron releasing substituents gave the
respective products 3a–h in high yields in a short reac-
tion time between 3 min and 9 min. Similarly, thiophene-
2-carbaldehyde reacted within 4 min to produce 3i in 90%
(Scheme 1). In all cases, the product precipitated from
the reaction mixture spontaneously and was purified
by simple crystallization from EtOH. To further explore
the procedure, malononitrile was replaced with ethyl
cyanoacetate. The use of two different aldehydes showed
that the reactions were successful but the final products
were obtained in relatively longer time periods (Scheme 2).
The structure of all products 3a–3k was elucidated based
on spectral analysis.
O
O
O
O
NaOH
NaOH
O
O
1
2
NC
CN
NH2
NH
O
CN
NC
O
CN
Ar
CN
Ar
O
O
Ar
Ar
Ar
Ar
O
O
O
O
O
3
3
3
Scheme 3ꢁ
conditions within a few minutes. The product precipitates
spontaneously.
The proposed mechanism is shown in Scheme 3. To Experimental
support the intermediary of 2, four different derivatives
Melting points are uncorrected. Fourier transform-infrared (FT-IR)
2a (Arꢀ=ꢀC6H5), 2c (Arꢀ=ꢀ4-ClC6H4), 2f (Arꢀ=ꢀ4-MeC6H4), and 2i
(Arꢀ=ꢀ2-thienyl) were synthesized independently and sub-
jected to the treatment with malononitrile. As expected,
the respective products 3a, c, f, i were obtained efficiently
in high yields and after short reaction times [80% (6 min),
83% (5 min), 75% (10 min) and 85% (5 min), respectively].
spectra were recorded using KBr disks on a Bruker Vector-22 spectro-
meter. NMR spectra were obtained on a Bruker Ultra Shield™ spectro-
1
meter at 500 MHz for H and 125 MHz for 13C in CDCl3 or DMSO-d6.
Elemental analyses were performed using a Thermo Finnigan Flash
EA 1112 instrument. Mass spectra were obtained on a Finnigan Mat
8430 instrument at ionization potential of 70 eV. TLC experiments
were carried out on pre-coated silica gel plates using petroleum ether/
EtOAc (4:1) as eluent. Ketone 1 was prepared as previously reported
[31]. Aldehydes were distilled or crystallized immediately before use.
Conclusion
An efficient procedure for the synthesis of a series
of dihydropyrano[3,2-d][1,3]dioxin heterocycles was
developed. The one-pot procedure is suitable for the
General procedure
To a solution of the aldehyde ArCHO (2.0 mmol) and 1 (130 mg,
preparation of various derivatives under sonochemical 1.0 mmol) in EtOH (2.0 mL) was added an aqueous solution of NaOH
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M.M. Mojtahedi et al.: Synthesis of dihydropyranodioxin-7-carbonitrilesꢀ
ꢀ93
(25%, 33 μL, 0.21 mmol). The resulting mixture was irradiated in a 3.76 (s, 6H, Me), 3.77 (s, 6H, Me), 4.25 (s, 1H, CHAr), 5.84 (s, 1H, =CH),
Sartorius Ultrasonic-homogenizer LABSONIC®P 230V/50 Hz instru- 6.53 (s, 2H, NH2), 6.87 (s, 2H, Ar), 6.91 (s, 2H, Ar); 13C NMR (DMSO-d6):
ment with a frequency of 24 KHz and nominal power of 460 W/cm2 δ 23.5, 25.5, 40.1, 56.0, 56.4, 56.7, 60.4, 60.5, 102.6, 103.0, 105.5, 106.0,
for 2 min until a yellowish precipitate of the intermediate 2 was 120.2, 125.8, 130.5, 133.7, 136.8, 137.2, 137.5, 138.3, 153.1, 153.4, 159.7; MS:
+
observed. At this point, malononitrile (100 mg, 1.5 mmol) or ethyl m/z 552 (M ), 486, 274, 232, 181; IR: 3315, 2963, 2197, 1645 cm−1. Anal.
cyanoacetate (170 mg, 1.5 mmol) was added and the mixture was Calcd for C29H32N2O9: C, 63.03; H, 5.84. Found: C, 62.91; H, 5.95.
irradiated for another 2 min. TLC showed that the starting materials
and the intermediate 2 were completely consumed. The product that
precipitated spontaneously from the reaction mixture was separated
by filtration and crystallized from EtOH.
(Z)-6-Amino-2,2-dimethyl-4-(4-methylbenzylidene)-8-(p-tolyl)-
4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile
(3f)ꢁYield
87%; mp 193–196°C; 1H NMR (DMSO-d6): δ 1.34 (s, 3H, Me), 1.58 (s, 3H,
Me), 2.31 (s, 3H, Me), 2.32 (s, 3H, Me), 4.22 (s, 1H, CHAr), 5.88 (s, 1H,
(Z)-6-Amino-4-benzylidene-2,2-dimethyl-8-phenyl-4,8-dihy- =CH), 6.93 (s, 2H, NH2), 7.16 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 7.17 (d, 2H, Jꢀ=ꢀ8.0 Hz,
dropyrano[3,2-d][1,3]dioxin-7-carbonitrile (3a)ꢁYield 94%; mp Ar), 7.19 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 7.46 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar); 13C NMR
1
198–200°C; H NMR (CDCl3): δ 1.39 (s, 3H, Me), 1.65 (s, 3H, Me), 4.27 (DMSO-d6): δ 21.5, 21.7, 24.2, 25.5, 40.1, 57.3, 102.9, 103.1, 126.1, 128.6,
(s, 1H, CHAr), 4.66 (s, 2H, NH2), 5.86 (s, 1H, =CH), 7.23 (t, 1H, Jꢀ=ꢀ7.5 Hz, 129.1, 130.0, 130.1, 131.5, 132.6, 134.5, 136.7, 137.4, 138.6, 139.4, 160.0;
Ar), 7.30–7.36 (m, 5H, Ar), 7.38–7.41 (m, 2H, Ar), 7.62 (d, 2H, Jꢀ=ꢀ7.5 Hz, MS: m/z 400 (M ), 334, 296, 156, 115; IR: 3426, 3315, 2203, 1637 cm−1.
+
Ar); 13C NMR (CDCl3): δ 23.9, 25.7, 41.2, 60.9, 102.7, 103.6, 119.6, 126.3, Anal. Calcd for C25H24N2O3: C, 74.98; H, 6.04. Found: C, 75.05; H, 6.11.
127.0, 128.2, 128.4, 128.8, 129.1, 129.2, 134.2, 135.3, 138.6, 140.6, 159.1;
+
MS: m/z 372 (M ), 270, 142, 114; IR: 3435, 3344, 2191, 1641 cm−1. Anal.
(Z)-6-Amino-4-(2-methoxybenzylidene)-8-(2-methoxyphenyl)-
2,2-dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile
(3g)ꢁYield 85%; mp 187–190°C; 1H NMR (DMSO-d6): δ 1.32 (s, 3H, Me),
Calcd for C23H20N2O3: C, 74.18; H, 5.41. Found: C, 73.95; H, 5.01.
(Z)-6-Amino-4-(2-chlorobenzylidene)-8-(2-chlorophenyl)-2,2- 1.53 (s, 1H, Me), 3.78 (s, 3H, OMe), 3.83 (s, 3H, OMe), 4.67 (s, 1H, CHAr),
dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile 6.24 (s, 1H, =CH), 6.87 (s, 2H, NH2), 6.91 (dd, 1H, Jꢀ=ꢀ7.5, 7.5 Hz, Ar),
(3b)ꢁYield 90%; mp 200–202°C; 1H NMR (CDCl3): δ 1.39 (s, 3H, Me), 1.62 6.95–7.00 (m, 3H, Ar), 7.15 (d, 1H, Jꢀ=ꢀ7.5 Hz, Ar), 7.17 (d, 1H, Jꢀ=ꢀ7.5 Hz,
(s, 3H, Me), 4.73 (s, 2H, NH2), 4.93 (s, 1H, CHAr), 6.26 (s, 1H, =CH), 7.14 Ar), 7.24 (dd, 1H, Jꢀ=ꢀ7.5, 8.0 Hz, Ar), 7.85 (d, 1H, Jꢀ=ꢀ8.0 Hz, Ar); 13C NMR
(ddd, 1H, Jꢀ=ꢀ1.5, 7.5, 7.5 Hz, Ar), 7.25–7.27 (m, 2H, Ar), 7.31 (dd, 1H, Jꢀ=ꢀ1.5, (DMSO-d6): δ 23.4, 25.4, 34.8, 55.9, 56.2, 56.3, 96.2, 102.3, 111.2, 112.0,
7.5 Hz, Ar), 7.33 (dd, 1H, Jꢀ=ꢀ1.5, 7.5 Hz, Ar), 7.40 (dd, 1H, Jꢀ=ꢀ1.5, 8.0 Hz, Ar), 120.4, 120.8, 121.2, 123.5, 126.5, 128.1, 129.1, 129.4, 129.6, 129.7, 134.1,
+
7.41 (dd, 1H, Jꢀ=ꢀ1.5, 8.0 Hz, Ar), 8.00 (dd, 1H, Jꢀ=ꢀ1.5, 8.0 Hz, Ar); 13C NMR 138.6, 156.4, 157.6, 160.2; MS: m/z 432 (M ), 343, 229, 172, 150; IR: 3436,
(CDCl3): δ 23.4, 25.3, 37.6, 59.5, 98.7, 102.6, 118.8, 126.4, 126.6, 127.3, 127.5, 3314, 2195, 1643 cm−1. Anal. Calcd for C25H24N2O5: C, 69.43; H, 5.59.
129.0, 129.4, 130.1, 130.2, 132.5, 133.0, 134.0, 134.1, 137.3, 139.3, 159.0; MS: Found: C, 69.59; H, 5.66.
+
m/z 441 (M ), 382, 347, 271, 240; IR: 3462, 3359, 2194, 1638 cm−1. Anal.
Calcd for C23H18Cl2N2O3: C, 62.60; H, 4.11. Found: C, 62.51; H, 4.15.
(Z)-6-Amino-4-(4-methoxybenzylidene)-8-(4-methoxyphenyl)-
2,2-dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile
1
(Z)-6-Amino-4-(4-chlorobenzylidene)-8-(4-chlorophenyl)-2,2- (3h)ꢁYield 89%; mp 212–216°C; H NMR (DMSO-d6): δ 1.27 (s, 3H,
dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbonitrile Me), 1.55 (s, 3H, Me), 3.75 (s, 6H, OMe), 4.26 (s, 1H, CHAr), 5.83 (s,
1
(3c)ꢁYield 95%; mp 212–216°C; H NMR (DMSO-d6): δ 1.33 (s, 3H, 1H, =CH), 6.77 (s, 2H, NH2), 6.91 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 6.92 (d, 2H,
Me), 1.57 (s, 3H, Me), 4.34 (s, 1H, CHAr), 5.88 (s, 1H, =CH), 7.02 (s, 2H, Jꢀ=ꢀ8.0 Hz, Ar),7.16 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 7.49 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar); 13C
NH2), 7.30 (d, 2H, Jꢀ=ꢀ8.5 Hz, Ar), 7.38 (d, 2H, Jꢀ=ꢀ8.5 Hz, Ar), 7.43 (d, 2H, NMR (DMSO-d6): δ 23.8, 25.2, 40.1, 55.5, 57.0, 102.4, 102.4, 114.4, 114.5,
Jꢀ=ꢀ8.5 Hz, Ar), 7.55 (d, 2H, Jꢀ=ꢀ8.5 Hz, Ar); 13C NMR (DMSO-d6): δ 2 3.7, 120.4, 125.6, 127.7, 129.3, 130.1, 133.7, 134.0, 137.1, 158.3, 159.0, 159.6; MS:
25.1, 40.2, 56.2, 101.6, 103.0, 120.1, 125.7, 129.0, 129.1, 130.2, 130.4, 131.2, m/z 432 (M ), 374, 330, 239, 187; IR: 3395, 3309, 2194, 1642 cm−1. Anal.
+
+
132.5, 133.8, 134.2, 139.3, 140.8, 159.7; MS: m/z 441 (M ), 382, 354, 240, Calcd for C25H24N2O5: C, 69.43; H, 5.59. Found: C, 69.67; H, 5.68.
205; IR: 3454, 32510, 2196, 1642 cm−1. Anal. Calcd for C23H18Cl2N2O3: C,
62.60; H, 4.11. Found: C, 62.66; H, 4.18.
(Z)-6-Amino-2,2-dimethyl-8-(thiophen-2-yl)-4-(thiophen-2-
ylmethylene)-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carboni-
1
(Z)-6-Amino-4-(2,4-dichlorobenzylidene)-8-(2,4-dichlorophe- trile (3i)ꢁYield 90%; mp 200–203°C; H NMR (DMSO-d6): δ 1.37 (s,
nyl)-2,2-dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-car- 3H, Me), 1.61 (s, 3H, Me), 4.65 (s, 1H, CHAr), 6.23 (s, 1H, =CH), 6.98–
bonitrile (3d)ꢁYield 96%; mp 230–232°C; 1H NMR (DMSO-d6): δ 1.37 7.03 (m, 3H, Ar), 7.04 (s, 2H, NH2), 7.09 (d, 1H, Jꢀ=ꢀ3.0, 1H, Ar), 7.45 (d,
(s, 3H, Me), 1.57 (s, 3H, Me), 4.83 (s, 1H, CHAr), 6.20 (s, 1H, =CH), 7.17 1H, Jꢀ=ꢀ5.0 Hz, Ar), 7.46 (d, 1H, Jꢀ=ꢀ5.0 Hz, Ar); 13C NMR (DMSO-d6): δ
(s, 2H, NH2), 7.38 (dd, 1H, Jꢀ=ꢀ2.0, 8.5 Hz, Ar), 7.46 (s, 1H, Ar), 7.47 (d, 23.5, 25.3, 36.0, 56.9, 98.4, 103.2, 120.1, 125.0, 126.2, 126.9, 127.0, 127.4,
+
1H, Jꢀ=ꢀ2.0 Hz, Ar), 7.62 (d, 1H, Jꢀ=ꢀ2.0 Hz, Ar), 7.63 (d, 1H, Jꢀ=ꢀ2.0 Hz, Ar), 133.6, 136.6, 137.2, 146.2, 159.7; MS: m/z 384 (M ), 326, 282, 254, 203,
7.97 (d, 1H, Jꢀ=ꢀ8.5 Hz, Ar); 13C NMR (DMSO-d6): δ 23.4, 25.3, 40.1, 54.9, 177; IR: 3452, 3339, 2188, 1686 cm−1. Anal. Calcd for C19H16N2O3S2: C,
97.2, 103.4, 119.7, 126.2, 127.9, 128.6, 129.3, 129.6, 131.4, 131.5, 131.7, 133.0, 59.35; H, 4.19; S, 16.68. Found: 59.51; H, 4.27, S, 16.74.
+
133.4, 134.1, 134.2, 137.6, 140.6, 160.0; MS: m/z 510 (M ), 415, 210, 147;
IR: 3438, 3315, 2204, 1655 cm−1. Anal. Calcd for C23H16Cl4N2O3: C, 54.15;
Ethyl (Z)-6-amino-4-(4-chlorobenzylidene)-8-(4-chlorophenyl)-
H, 3.16. Found: 54.23; H, 3.22.
2,2-dimethyl-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carbox-
1
ylate (3j)ꢁYield 90%; mp 170–172°C; H NMR (CDCl3): δ 1.13 (t, 3H,
(Z)-6-Amino-2,2-dimethyl-4-(3,4,5-trimethoxybenzylidene)-8- Jꢀ=ꢀ7.0 Hz, Me), 1.28 (s, 3H, Me), 1.61 (s, 3H, Me), 4.01–4.05 (m, 2H,
(3,4,5-trimethoxyphenyl)-4,8-dihydropyrano[3,2-d][1,3]dioxin- CH2), 4.40 (s, 1H, CHAr), 5.78 (s, 1H, =CH), 6.39 (br s, 2H, NH2), 7.21
1
7-carbonitrile (3e)ꢁYield 90%; mp 160–164°C; H NMR (DMSO-d6): (d, 2H, Jꢀ=ꢀ7.5 Hz, Ar), 7.25 (d, 2H, Jꢀ=ꢀ7.5 Hz, Ar) 7.27 (d, 2H, Jꢀ=ꢀ7.5 Hz,
δ 1.42 (s, 3H, Me), 1.60 (s, 3H, Me), 3.66 (s, 3H, Me), 3.67 (s, 3H, Me), Ar), 7.52 (d, 2H, Jꢀ=ꢀ7.5 Hz, Ar); 13C NMR (CDCl3): δ 14.2, 23.2, 25.5, 39.7,
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94ꢀ
59.6, 76.8, 101.3, 102.2, 125.1, 128.1, 128.5, 129.4, 129.8, 131.7, 132.3, 133.6,
[9] Ewes, W. A.; Badr, S. M. I.; Eisa, H. M.; Nasr, M. N. A. Molecular
modeling and synthesis of new 1,5-diphenylpyrazoles as breast
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+
136.5, 139.1, 142.1, 159.3, 169.0; MS: m/z 487 (M ), 429, 376, 272, 176; IR:
3387, 3292, 1660, 1594 cm−1. Anal. Calcd for C25H23Cl2NO5: C, 61.49; H,
4.75. Found: C, 61.59; H, 4.82.
[10] Napoleon, A. A.; Nawaz Khan, F.-R.; Jeong, E. D.; Chung, E. H.
Potential anti-tubercular agents: hexahydro-3-phenyl indazol-
2-yl(pyridin-4-yl)methanones from anti-tubercular drug iso-
niazid and bis(substituted-benzylidene)cycloalkanones. Chin.
Chem. Lett. 2015, 26, 567–571.
Ethyl (Z)-6-amino-2,2-dimethyl-4-(4-methylbenzylidene)-8-(p-
tolyl)-4,8-dihydropyrano[3,2-d][1,3]dioxin-7-carboxylateꢀ(3k)ꢁ
1
Yield 89%; mp 182–184°C; H NMR (CDCl3): δ 1.13 (t, Jꢀ=ꢀ7.0 Hz, 3H,
Me), 1.29 (s, 3H, Me), 1.62 (s, 3H, Me), 2.33 (s, 3H, Me), 2.35 (s, 3H, Me),
3.98–4.09 (m, 2H, CH2), 4.37 (s, 1H, CHAr), 5.80 (s, 1H, =CH), 6.32 (br [11] Kumar, R. R.; Perumal, S.; Carlos Menéndez, J.; Yogeeswari, P.;
s, 2H, NH2), 7.08 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 7.13 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar) 7.16
(d, 2H, Jꢀ=ꢀ8.0 Hz, Ar), 7.51 (d, 2H, Jꢀ=ꢀ8.0 Hz, Ar); 13C NMR (CDCl3): δ
14.2, 21.1, 21.2, 23.3, 25.5, 39.7, 59.4, 76.8, 101.9, 102.1, 125.2, 128.0, 128.5,
Sriram, D. Antimycobacterial activity of novel 1,2,4-oxadiazole-
pyranopyridine/chromene hybrids generated by chemoselec-
tive 1,3-dipolar cycloadditions of nitrile oxides. Bioorg. Med.
Chem. 2011, 19, 3444–3450.
128.6, 129.1, 132.5, 135.9, 136.7, 138.3, 140.6, 159.4, 169.3; MS: m/z 447
+
(M ), 389, 356, 232,156; IR: 3400, 3294, 1659, 1592 cm−1. Anal. Calcd for [12] Reddy, C. R.; Reddy, M. D. A metal-free tandem C–C/C–O bond
C27H29NO5, C, 72.46; H, 6.63. Found: C, 72.31; H, 6.80.
formation approach to diversely functionalized tetrasubsti-
tuted furans. J. Org. Chem. 2014, 79, 106–116.
[13] Reddy, M. D.; Fronczek, F. R.; Watkins, E. B. Rh-catalyzed, regi-
oselective, C–H bond functionalization: access to quinoline-
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[14] Reddy, M. D.; Watkins, E. B. Palladium-catalyzed direct aryla-
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Acknowledgment: We are grateful to the Research Coun-
cil at CCERCI for the financial support of this work
(CCERCI-1395-109).
[15] Mahdavinia, G. H.; Bigdeli. M. A.; Kooti, F. DABCO catalyzed
synthesis of new 2-amino-8-arylidene-4-aryl-5,6,7,8-tetrahy-
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