Pyridine-functionalized MCM-41 as an efficient and recoverable catalyst for the synthesis of pyran annulated heterocyclic systems

Article abstract of DOI:10.1248/cpb.58.270

Pyridine-functionalized MCM-41 catalyzed reactions between tetracyanoethylene and various activated CH-acid compounds are described. These reactions afford the corresponding pyran annulated heterocyclic ring systems in high yields at room temperature within a few minutes. The work-up procedure is very simple and the products do not require further purification. The catalyst can be recycled and reused for several times without observable loss of performance.

Full text of DOI:10.1248/cpb.58.270

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Chem. Pharm. Bull. 58(2) 270—272 (2010)
Vol. 58, No. 2
Pyridine-Functionalized MCM-41 as an Efficient and Recoverable
Catalyst for the Synthesis of Pyran Annulated Heterocyclic Systems
Ahmad SHAABANI,* Mostafa MOHAMMADPOUR AMINI, Sabrieh GHASEMI, Rahim GHADARI,
Ali Hossein REZAYAN, Yousef FAZAELI, and Shahzad FEIZI
Department of Chemistry, Shahid Beheshti University; G.C., P.O. Box 19396–4716, Tehran, Iran.
Received November 5, 2009; accepted November 25, 2009; published online November 30, 2009
Pyridine-functionalized MCM-41 catalyzed reactions between tetracyanoethylene and various activated
CH-acid compounds are described. These reactions afford the corresponding pyran annulated heterocyclic ring
systems in high yields at room temperature within a few minutes. The work-up procedure is very simple and the
products do not require further purification. The catalyst can be recycled and reused for several times without
observable loss of performance.
Key words tetracyanoethylene; CH-acid; pyran; pyridine-functionalized MCM-41
Pyrans and their derivatives are of considerable interest NH2, pyridine and cyclopentadiene ligands, amongst oth-
because of their wide range of biological activities, such as ers.16,17)
spasmolytic, diuretic, anti-coagulant, anti-cancer, and anti-
In continuation of our research interest to synthesis such
anaphylactic activity.1—4) In addition, they can be used as as coumarins, pyrans, diazepines and quinolizines and also
cognitive enhancers, for the treatment of neurodegenerative introduce new catalysts for organic reactions,18—25) in this ar-
disease, including Alzheimer’s disease, amyotrophic lateral ticle we developed an efficient method for synthesis of pyran
sclerosis, Huntington’s disease, Parkinson’s disease, AIDS annulated heterocyclic ring systems in the presence of pyri-
associated dementia and Down’s syndrome as well as for the dine-functionalized MCM-41 (PF-MCM-41) as a recyclable
treatment of schizophrenia and myoclonus.5) 4H-Pyrans also catalysts, in high yield at room temperature (Chart 1).
constitute the structural unit of a series of natural products.6,7)
Catalyst Preparation For the preparation of pyridine-
Tetracyanoethylene (TCNE) is the simplest of the per- functionalized MCM-41 a procedure similar to functionaliz-
cyanoalkenes (cyanocarbons). Due to four powerful electron- ing by bipyridine was used.26,27) A solution of 4-methyl-pyri-
withdrawing cyano groups, the C–C double bond is highly dine was added to a THF solution of lithium diisopropyl-
electron-deficient and it is strongly electrophilic reagent. amine. After 2 h the brown solution was cooled to ꢀ20 °C
TCNE undergoes two principal types of reaction, namely, ad- and then MCM-41 grafted with chloropropylsilyl groups was
dition to its double bond and replacement of a cyano group. added. After 72 h, the reaction mixture was treated with the
TCNE has received an extensive amount of study and the mix of ice and water. The solution was filtered off and the
chemistry of this compound has been reviewed several pale solid washed three times with 15 ml aliquots of ethanol,
times.8—10)
three times with 15 ml aliquots of diethyl ether, and dried
The mesoporous molecular sieves such as MCM-41 which under reduced pressure at room temperature for several hours
discovered by Mobil researchers in 1992, have large and uni- (Chart 2).
form pore sizes, ultrahigh surface areas, large pore volume
The elemental analysis (CHN: C, 2.05; H, 0.30; N, 0.27)
and rich silanol groups in the inner walls. The developments shows that substitution of the chlorine by the anion [4-CH2-
of mesoporous silicas such as MCM-41 have generated inter- pyridine] gave a mesoporous silica containing ca. 0.2 mmol
est due to their potential applications such as catalysts, cata- pyridyl groups per gram. IR (KBr, n/cmꢀ1): 3440 s, 2925 m,
lyst supports, separation media, and host materials for inclu- 1640 m, 1596 m, 1554 m, 1071 vs., 954 s, 866 m, 799 s, 459 s.
sion compounds.11—13) Furthermore, because of special tex- The low angle powder XRD patterns of MCM-41 grafted
ture and properties of MCM-41, it has great potential as a with chloropropylsilyl (Fig. 1a) and pyridine (Fig. 1b) groups
matrix for immobilizing homogeneous catalysts. Other ad- showed that the mesoporous structure of MCM-41 retained
vantages for mesoporous are: (i) easy modification with or- and high quality materials obtained.
ganic groups and metal complexes, (ii) readily creating dis-
crete and uniform active sites, (iii) easy access for substrates Results and Discussion
involving bulky molecule.12,14)
In an initial experiment, the reaction of TCNE 1 with
Amorphous silica, alumina and other inorganic oxides furan-2,4(3H,5H)-dione (tetronic acid) 2 in the presence of
have found widespread use as supports for the immobiliza- PF-MCM-41 (0.01 g) in CH2Cl2 afforded the 2-amino-5-oxo-
tion of catalytically active sites and photo- and electro-active
species. These materials endowed with hydroxyl-rich surface
which facilitate derivatization. In order to functionalize a sil-
ica surface, for example, a molecule containing a ligand
group, or a group that may be readily converted to a ligand
group, is reacted with the surface silanol groups. One ap-
proach is to use silane coupling agents.15) Howell and co-
Chart 1. Reaction between TCNE and Tetronic Acid in the Presence of
workers used functional alkoxysilanes to anchor PPh2, CN, PF-MCM-41 as Catalyst
© 2010 Pharmaceutical Society of Japan
∗ To whom correspondence should be addressed. e-mail: a-shaabani@cc.sbu.ac.ir.

February 2010
271
Chart 2. Preparation of Catalyst
Fig. 1. XRD Patterns of Chloropropylsilyl (a) and Pyridine (b) Function-
alized MCM-41
5H-furo[3,4-b]pyran-3,4,4(7H)-tricarbonitrile 3a in 80%
yield. Similar reactivity was observed with other cyclic-1,3-
dicarbonyl compounds such as cyclopentane-1,3-dione and
cyclohexane-1,3-dione; results are summarized in Fig. 2.
In view of the success of the above mentioned reactions,
we explored the use of 5,5-dimethylcyclohexane-1,3-dione
(dimedone), 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-tri-
one, 4-hydroxy-6-methyl-2H-pyran-2-one, 4-hydroxy-2H-
chromen-2-one and 4-hydroxy-1-methylquinolin-2(1H)-one
as activated CH-acid. Treatment of 5,5-dimethylcyclohexane-
1,3-dione, 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione, 4-
hydroxy-6-methyl-2H-pyran-2-one, 4-hydroxy-2H-chromen-
2-one or 4-hydroxy-1-methylquinolin-2(1H)-one with TCNE
1 in the presence of PF-MCM-41 in CH2Cl2 at room temper-
ature led to the formation of the corresponding pyran annu-
lated heterocyclic systems in high yields (Fig. 2, products
3d—h).
Fig. 2. Reaction of TCNE with Various b-Dicarbonyl Activated CH-Acids
in the Presence of a Catalytic Amount of Pyridine-Functionalized MCM-41
To illustrate the role of catalyst, the reaction of TCNE 1
with dimedone was studied in the absence of PF-MCM-41
catalyst. The yield of product under similar reaction condi-
tions after 15 min was trace.
A mechanistic rationalization for the reaction is provided
in Chart 3.
In order to obtain the best media, we have examined vari-
ous solvents such as H2O, EtOH, CH3CN, C6H5CH3, n-
Hexan and CH2Cl2 in the presence of PF-MCM-41 catalyst.
Test reaction was carried out by mixing tetracyanoethylen
(0.13 g, 1 mmol) and dimedone (0.13 g, 1.10 mmol) in vari-
ous solvents in the presence of 0.01 g of PF-MCM-41. As
Chart 3. Proposed Pathway
can be seen from Table 1, CH2Cl2 is the best solvent respect used again. This procedure was carried out for four times.
to yield and short reaction time. In the case of H2O, the reac- Results of these successive reactions are shown in Table 2. It
tion time is long for the reasonable yield (Table 1, Entry 1).
is clear that by successive use of catalyst no decrease in reac-
Recyclability of the catalyst was examined too. For this tivity or performance can be seen.
reason, catalyst which was recovered from reaction between
One of the aims of the present investigation is to solve the
TCNE and tetronic acid by filtration was washed with 5 ml problems of using homogeneous catalyst such as separation
CH2Cl2; after drying the catalyst in oven (70 °C, 24 h), it was and regeneration. Ease of separation is one of the most im-

272
Vol. 58, No. 2
NH2). 13C-NMR (75 MHz, DMSO-d6) dC (ppm): 49.28, 67.30, 93.23 (C4,
C3, C7), 112.61 (CN), 116.46 (CN), 141.20 (C5), 160.91, 167.01,
172.00(C6, C2, C9). MS, m/z (%): 228 (Mꢂ, 20), 184 (40), 158 (100), 132
(55), 106 (30), 90 (35), 43 (60). Anal. Calcd for C10H4N4O3: C, 52.64; H,
1.77; N, 24.56. Found: C, 52.54; H, 1.73; N, 24.58.
Table 1. Effect of Solvent on the Reaction Times and Yieldsa)
Preparation of PF-MCM-41
A
solution of 4-methyl-pyridine
(8.0 mmol) in THF (40 ml) was added to a THF solution of lithium diiso-
propylamine (8.0 mmol). After 2 h the brown solution was cooled to ꢀ20 °C
and then MCM-41 grafted with chloropropylsilyl groups was added (2.0 g).
After 72 h, the reaction mixture was treated with the mix of ice and water.
The solution was filtered off and the pale solid washed three times with
15 ml aliquots of ethanol, three times with 15 ml aliquots of diethyl ether,
and dried under reduced pressure at room temperature for 48 h. Desired PF-
MCM-41 was obtained quantitatively.
Entry
Solvent
Time
Yield (%)
1
2
3
4
5
6
H2O
EtOH
CH3CN
C6H5CH3
n-Hexan
CH2Cl2
16 h
16 h
16 h
16 h
16 h
15 min
70
60
55
50
40
All of the products are known compounds (except product 3a), which
90, 92, 90, 92, 94
1
were characterized by IR, H, 13C-NMR, and mass spectra data. Their melt-
ing points were compared with literature reports, too.23)
a) Dimedone (1.1 mmol), tetracyanoethylen (1.0 mmol) in the presence of PF-
MCM-41 (0.01 g) at room temperature in various solvents.
Acknowledgement We gratefully acknowledge the financial support
from the Research Council of Shahid Beheshti University.
Table 2. Recycle of Catalysta)
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carried out by filtration. After drying, it was reused for sub-
sequent reactions (Table 2). Thus, this process could be also
interesting for large-scale synthesis.
Conclusions
In conclusion, we have developed a rapid and very effi-
cient pyridine-functionalized MCM-41-catalyzed approach
for the synthesis of pyran annulated heterocyclic ring sys-
tems under mild reaction conditions with excellent yields.
The present method has the advantages that not only the cat-
alyst can be recycled and reused for several times without
loss of performance, but also the substances can be mixed
without any modification. The work-up procedure is very
simple and the products do not require further purification.
The simplicity of the present procedure makes it an interest-
ing alternative to other approaches.
Experimental
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Techniques and Materials Melting points were measured on an Elec-
trothermal 9100 apparatus and are uncorrected. Mass spectra were recorded
on a FINNIGAN-MAT 8430 mass spectrometer operating at an ionization
potential of 70 eV. IR spectra were recorded on a Shimadzu IR-470 spec-
trometer. 1H- and 13C-NMR spectra were recorded on a BRUKER DRX-300
AVANCE spectrometer at 300.13 and 75.47 MHz. NMR spectra were ob-
tained in DMSO-d6. The chemicals used, were purchased from Merck and
Fluka Chemical Companies.
Typical Experimental Procedure. Preparation of 2-Amino-5-oxo-5H-
furo[3,4-b]pyran-3,4,4(7H)-tricarbonitrile (3a) To a magnetically stirred
solution of tetracyanoethylene (0.13 g, 1.0 mmol) and PF-MCM-41 (0.01 g),
in CH2Cl2 (15 ml), a solution of tetronic acid (0.10 g, 1.0 mmol) in CH2Cl2
(2 ml) was added drop wise at room temperature and the reaction mixture
was stirred for 15 min. After completion of the reaction, solid catalyst was
separated from reaction mixture by filtration. Then, solvent was removed
under reduced pressure and the residue was crystallized from CH2Cl2/n-
hexane 1 : 2 to yield 0.241 g of 3a as a pink powder (90%). mp 198—200 °C.
IR (KBr) (nmax, cmꢀ1): 3424, 3338 (NH2), 2210 (CN), 1741 (CꢁO). 1H-
NMR (300 MHz, DMSO-d6) dH (ppm): 5.14 (2H, s, CH2), 8.76 (2H, bs,
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