A convenient one-pot synthesis of new chromeno[3,4-c]chromene and chromeno[3,4-c]pyridine derivatives in the presence of high surface area of magnesium oxide

Article abstract of DOI:10.1016/j.cclet.2012.10.007

In this investigation a new strategy involves the one-pot, three-component reaction of malononitrile, salycilaldehyde and phenol derivatives in the presence of high surface area of MgO is extended to the formation of chromeno[3,4-c]chromene derivatives in good to excellent yields in a short reaction time. Also, the three component reactions of an aldehyde such as salycilaldehyde and ketones with malononitril for the formation of chromeno[3,4-c]pyridines are investigated.

Full text of DOI:10.1016/j.cclet.2012.10.007

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 1327–1330
www.elsevier.com/locate/cclet
A convenient one-pot synthesis of new chromeno[3,4-c]chromene
and chromeno[3,4-c]pyridine derivatives in the presence of high
surface area of magnesium oxide
Iman Mohammadzadeh a, , Hassan Sheibani
b
*
a University of Applied Science and Technology of Kerman, Kerman 7618841681, Iran
b Department of Chemistry, Shahid Bahonar University of Kerman, Kerman 76169, Iran
Received 31 May 2012
Available online 16 November 2012
Abstract
In this investigation a new strategy involves the one-pot, three-component reaction of malononitrile, salycilaldehyde and phenol
derivatives in the presence of high surface area of MgO is extended to the formation of chromeno[3,4-c]chromene derivatives in
good to excellent yields in a short reaction time. Also, the three component reactions of an aldehyde such as salycilaldehyde and
ketones with malononitril for the formation of chromeno[3,4-c]pyridines are investigated.
# 2012 Iman Mohammadzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Salycilaldehyde; Chromeno[3,4-c]chromenes; 2-Amino-4-aryl pyridylcyanides malononitrile
Structures containing the pyridine and chromene skeleton are rapidly gaining importance in synthetic and natural
product chemistry. These compounds are useful synthons in organic synthesis and can be used as precursors of a wide
variety of biologically active natural products [1]. There has been a considerable interest in the 2-oxo-2H-chromene
(coumarin) ring system, both with regard to natural product chemistry, and to the pharmacological activities of several
of its derivatives [2–4]. In addition, other 2-oxo-2H-chromenes are an important class compounds that found as the
main components of many naturally occurring products employed as cosmetics, pigments and utilized as potential
biodegradable agrochemicals [5,6].
Multi-component reactions (MCRs) play an important role in combinatorial chemistry because of its ability to
synthesize small drug-like molecules with several degrees of structural diversity.
This reaction tool allows compounds to be synthesized in a few steps and usually in a one-pot operation. Another
typical benefit from these reactions is simplified purification, because all of the reagents are incorporated into the final
product. We have recently reported a one-pot three-component synthesis of benzo[h]chromenes derivatives and which
were catalyzed by magnesium oxide (MgO) as heterogeneous base catalyst [7,8]. Heterogeneous catalysts are
advantageous over conventional homogeneous catalysts as they can be easily recovered from the reaction mixture by
simple filtration and can be reused after activation, thereby making the process economically viable. Among the
* Corresponding author.
E-mail address: Iman.mz@gmail.com (I. Mohammadzadeh).
1001-8417/$ – see front matter # 2012 Iman Mohammadzadeh. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.10.007

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I. Mohammadzadeh, H. Sheibani / Chinese Chemical Letters 23 (2012) 1327–1330
heterogeneous basic catalysts, magnesium oxide is a versatile material used as catalyst for several base catalyzed
organic transformations [9], toxic waste remediation, and as additive in refractory, paint, and superconductor products
[10].
1. Results and discussion
In the present work, we report an efficient one-pot, three-component reaction protocol for the synthesis of
chromeno[3,4-c]chromene derivatives (4a, b, 6 and 8) in the presence of high surface area of magnesium oxide as a
highly effective heterogeneous base catalyst. This protocol offers flexibility in tuning the molecular complexity and
diversity. The reactions proceeded to completion almost instantaneously, and pure product was obtained, without
using any chromatographic techniques, simply by recrystallization from ethanol (Scheme 1).
In a similar manner we have prepared chromeno[3,4-c]pyridine derivatives (10 and 12) from the three component
reactions of salicylaldehyde, malononitrile and ketones such as acetophenone and cyclohexanone in the presence of
high surface area MgO in good to excellent yields and in a short experimental time (Scheme 2).
High surface area magnesium oxide (MgO) was obtained using a novel but simple procedure by rehydrated
Mg(OH)2 at 450 8C for 2 h. A calcinations temperature of 400–500 8C gave maximum conversion when the catalyst
was calcined above 500 8C, the activity of Mgo decreased and continued to decrease as the calcinations temperature
increased. The maximum surface area was obtained after calcining the samples at 400–500 8C [11]. The preparation
and activation of this catalyst is simple and does not need cumbersome apparatus compare to the alternative catalysts,
and may offer sufficient compensation to make MgO the base catalyst of choice. As shown in Table 1, first we
examined three-component reactions in an organic solvent (DMF) at reflux in absence catalyst. The reactions were too
slow and the yields were not high. Also, the three-component reactions were carried out in the presence of two types of
magnesium crystals [commercial MgO (CM-MgO) and high surface area MgO (HSA-MgO)] in DMF as an organic
solvent at reflux condition. High surface area MgO was found to be more active than commercial MgO (CM-MgO).
The complete process represents an example of the one-pot and sequential steps reaction (often referred to as
tandem or cascade reaction) where reagents and catalysts are mixed together and experimental conditions are set up in
such a way to promote the reaction cascade. The three-component reaction of malononitrile, salicylaldehyde and 1,3-
dinucleophiles involve both Knoevenagel condensation and Michael addition. Thus the arylidenemalononitrile A
containing an electron-poor C C double bond is produced by rapid Knoevenagel condensation of malononitrile with
the salicylaldehyde, the formation of the salicylidenemalononitrile was monitored by TLC (n-hexane/diethyl ether as
eluent). The second step is followed by Michael addition of 1,3-dinucleophiles such as phenol derivatives or
O
O
R
OH
H
MgO
DMF
NH
H
CH2(CN)2
4a: R= H
4b: R= OH
+
+
O
NH2
OH
R
3
1
2
4
OH
O
O
Cl
H
MgO
DMF
NH
+
CH2(CN)2
+
OH
O
NH2
Cl
6
5
O
O
OH
MgO
DMF
NH
NH2
H
+
+
CH2(CN)2
O
OH
7
8
Scheme 1.

I. Mohammadzadeh, H. Sheibani / Chinese Chemical Letters 23 (2012) 1327–1330
1329
O
O
O
CH3COO-NH4+
DMF/MgO
H
NH
+
+
CH2(CN)2
CH2(CN)2
+
OH
N
NH2
9
10
O
O
O
CH3COO-NH4+
DMF/MgO
H
NH
+
OH
N
NH2
11
12
Scheme 2.
Table 1
Synthesis of compounds 4, 6, 8, 10 and 12 under different reaction conditions.a
Compd.
Without catalyst
Time (min)
Commercial (MgO)
Time (min)
High surface area (MgO)
Yield (%)
Yield (%)
Time (min)
Yield (%)
4a
4b
6
120
180
180
150
240
240
50
40
50
45
55
60
15
30
30
25
30
30
78
60
65
60
50
55
9
12
10
9
90
80
92
90
89
8
10
12
10
8
a
Prepared by experimental procedure cited in Ref. [12].
acetophenonimine and cyclohexan. Imine, followed by cyclization and proton shift affords the final product (Scheme
3). We have separately studied also the effect of catalytic activity of MgO on the Knoevenagel condensation of
malononitrile and aldehydes to afford the a-cyanocinnamonitrile derivatives and Michael addition of nucleophiles
with arylidinmonitriles in same conditions. The catalyst plays a crucial role in the success of the reaction in terms of
the rate and the yields [11].
1
Structures 4a–b, 6, 8, 10 and 12 were determined on the basis of their mass spectra, H and 13C NMR and IR
spectroscopic data [12]. Melting points were measured on a Gallenkamp melting point apparatus and are uncorrected.
IR spectra were measured on a Mattson 1000 FT-IR spectrometer. The proton and carbon NMR spectra were recorded
with a BRUKER DRX-500 AVANCE spectrometer at 500 and 125.77 MHz, respectively. Mass spectra (MS) were
recorded on a Shimadzu QP 1100EX mass spectrometer operating at an ionization of 70 eV.
In conclusion, we have developed a simple and efficient method for the synthesis of poly heterocyclic compounds
which having a chromeno and pyridine nucleus in the presence of MgO, a highly effective heterogeneous base catalyst.
OH
OH
CN
CN
CN
HC
H
+
H
CN
O
---------Mg+2-------------------O2----------
OH
CN
O
H
T.M
+
NH
O
O
O
CN
NC
H
H
H
N
O
NH
------O2- -------Mg2+---- -------O2------------Mg2+-------- -------O2---------Mg2+---
--Mg2+---- ---O2-----
Scheme 3.

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I. Mohammadzadeh, H. Sheibani / Chinese Chemical Letters 23 (2012) 1327–1330
Advantages of the strategy include simple catalyst preparation, mild reaction temperature, easy recovery, and
reusability of the catalyst with consistent activity and short reaction times.
Acknowledgment
The authors express appreciation to the Shahid Bahonar University of Kerman Faculty Research Committee Fund
for its support of this investigation.
References
[1] X. Zhang, B. Hinkel, L. Ballantyne, et al. J. Heterocycl. Chem. 34 (1997) 1061.
[2] K.T. Potts, M.O. Dery, R.K. Kullinig, J. Chem. Soc., Chem. Commun. (1987) 840.
[3] J.R. Li, L.J. Zhang, X.Q. Yang, et al. Chin. Chem. Lett. 19 (2008) 15.
[4] N. Pandeya, P. Yogeeswari, D.S. Ram, Gopal. Nath. Bollettino Chimico Farmaceutico 8 (1998) 137.
[5] H. Miao, Z. Yang, Org. Lett. 2 (2000) 1765.
[6] S. Kadis, A. Ciegler, S. Ajl, Microbial Toxins, vol. 7, Academic Press, New York, 1972, p. 1 (Chapter).
[7] H. Sheibani, K. Saidi, M. Abbasnejad, et al. Arab. J. Chem., (2013) in press.
[8] H. Sheibani, M. Seifi, Catal. Lett. 126 (2008) 275.
[9] H. Hattori, Chem. Rev. 95 (1995) 537.
[10] Y. Ding, G. Zhang, H. Wu, et al. Chem. Mater. 13 (2001) 435.
[11] C.L. Xu, J.K. Bartley, D.I. Enache, et al. Synthesis 19 (2005) 3468.
[12] General procedure for compounds 4a-b, 6, 8, 10 and 12: A mixture of 2 mmol of starting materials in DMF (20 mL) in absence catalyst or in the
presence of two types of magnesium oxide (50 mg) [commercial MgO (CM-MgO) and high surface area MgO (HSA-MgO)] was refluxed with
stirring for the times reported in Table 1. After completion of the reaction, MgO was removed by filtration and excess DMF was distilled off.
The crude product so obtained was recrystallized from ethanol to afford the pure product. 4a: Yellow crystals; mp: 228–230 8C; IR (KBr,
cmÀ1): 3453, 3329 (NH2), 1666 (C N), 1594 (C C); 1H NMR (500 MHz, DMSO-d6): d 6.26 (1H, CH), 6.35–8.34 (11H, Ar and NH2). 13
C
NMR (125 MHz, DMSO-d6): d 159.63, 157.32, 153.12, 150.83, 134.06, 128.59, 128.92, 124.63, 124.20, 122.21, 117.39, 114.70, 104.60, 70.80,
46.90; MS m/z: 264 (M+, 10), 237 (5), 221 (6), 111 (35), 97 (50), 85 (45), 71 (70), 57 (100), 43 (72). 4b: Yellow crystals; mp 242–248 8C; IR
(KBr, cmÀ1): 3460–3329 (NH2), 1666 (C N), 1594 (C C); 1H NMR (500 MHz, DMSO-d6): d 7.20–8.35 (11H, Ar, OH and NH2), 4.50 (1H,
CH); 13C NMR (125 MHz, DMSO-d6): d 165.22, 161.00, 156.20, 152.17, 149.22, 134.20, 129.00, 126.22, 124.36, 120.22, 116.42, 115.23,
112.20, 111.22, 96.90, 56.22; MS, m/z: 280 (M+, 8), 253 (4), 237 (6), 111 (35), 97 (50), 85 (45), 71 (70), 57 (100), 43 (72). 6: Yellow crystals;
mp 295–298 8C; IR (KBr, cmÀ1): 3414–3325 (NH2), 1666 (C N), 1594 (C C); 1H NMR (500 MHz, DMSO-d6): d 6.50–8.40 (12H, Ar and
NH2), 5.8 (1H, CH); 13C NMR (125 MHz, DMSO-d6): d 160.28, 159.22, 152.30, 150.23, 149.21, 148.20, 134.24, 133.22, 130.42, 129.12,
125.28, 120.12, 119.16, 118.10, 116.22, 112.07, 102.32, 98.20, 55.20; MS m/z:350 (M+ + 2, 3), 348 (M+, 15), 321 (8), 305 (6) 161 (52), 111
(25), 97 (30), 71 (36), 57 (100), 43 (60). 8: Yellow crystals; mp 289–292 8C; IR (KBr, cmÀ1): 3404, 3329 (NH2), 1666 (C N), 1594 (C C); 1H
NMR (500 MHz, DMSO-d6): d 6.15–7.75 (13H, Ar and NH2), 6.12 (1H, CH); 13C NMR (125 MHz, DMSO-d6): d 160.28, 157.69, 152.32,
150.78, 132.74, 130.38, 129.95, 129.68, 128.84, 128.22, 127.04, 124.87, 124.65, 123.34, 122.92, 121.18, 118.23, 117.11, 116.94, 71.62, 30.31;
MS m/z: 314 (M+, 8), 287 (6), 271 (5), 127 (60), 97 (35), 71 (40), 57 (100), 43 (65). 10: Red crystals; mp 233–235 8C; IR (KBr, cmÀ1): 3205–
3358 (NH2), 1691 (C N), 1542 (C C); 1H NMR (500 MHz, DMSO-d6): d 7.49–8.76 (13H, m, Ar and NH2); 13C NMR (125 MHz, DMSO-
d6): d 163.09, 162.69, 156.37, 152.65, 139.55, 138.75, 134.06, 131.59, 129.68, 128.63, 126.20, 126.14, 118.21, 105.68; MS m/z: 287 (M+, 5),
260 (3), 244 (4), 97 (42), 85 (32), 71 (58), 57 (100), 43 (62). 12: Red crystals; mp 240–241 8C; IR (KBr, cmÀ1): 3379–3304 (NH2), 1617
(C N), 1517 (C C); 1H NMR (500 MHz, DMSO-d6): d 6.99–8.37 (7H, Ar and NH2), 1.06–3.00 (4H, CH2); 13C NMR (125 MHz, DMSO-d6):
d 164.52, 161.88, 160.72, 137.20, 132.92, 129.90, 125.57, 119.45, 118.82, 117.59, 75.66, 35.54, 30.46, 23.74, 22.37; MS m/z: 265 (M+, 15), 238
(9), 222 (8), 97 (55), 85 (60), 71 (65), 57 (100), 43 (68).