One-pot, three-component synthesis of highly substituted pyridines and 1,4-dihydropyridines by using nanocrystalline magnesium oxide

Article abstract of DOI:10.1007/s12039-010-0007-x

One pot, three component synthesis of 2-amino-4-aryl-3,5-dicyano-6- sulfanylpyridines and the corresponding 1,4-dihydropyridines are from readily accessible starting materials is described. Simply heating of an ethanolic solution of structurally diverse aldehydes with various thiols and malononitrile in the presence of nanocrystalline magnesium oxide provides the highly substituted pyridine derivatives in moderate to high yields, each representing a privileged medicinal scaffold with their structural motif. After completion of the reaction, the catalyst can be recovered efficiently and reused with constintent activity. Indian Academy of Sciences malononitrile; nanocrystalline magnesium oxide.

Full text of DOI:10.1007/s12039-010-0007-x

J. Chem. Sci., Vol. 122, No. 1, January 2010, pp. 63–69. © Indian Academy of Sciences.
One-pot, three-component synthesis of highly substituted pyridines
and 1,4-dihydropyridines by using nanocrystalline magnesium oxide
1,
1
2
M LAKSHMI KANTAM *, KOOSAM MAHENDAR and SURESH BHARGAVA
1
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology,
Hyderabad 500 007
2
School of Applied Sciences, RMIT University, Melbourne, Australia
e-mail: mlakshmi@iict.res.in
Abstract. One pot, three component synthesis of 2-amino-4-aryl-3,5-dicyano-6-sulfanylpyridines and
the corresponding 1,4-dihydropyridines are from readily accessible starting materials is described. Sim-
ply heating of an ethanolic solution of structurally diverse aldehydes with various thiols and malononi-
trile in the presence of nanocrystalline magnesium oxide provides the highly substituted pyridine
derivatives in moderate to high yields, each representing a privileged medicinal scaffold with their struc-
tural motif. After completion of the reaction, the catalyst can be recovered efficiently and reused with
constintent activity.
Keywords. Multicomponent reactions (MCRs); pyridines; 1,4-dihydropyridines; aldehydes; thiols;
malononitrile; nanocrystalline magnesium oxide.
5
1. Introduction
include Vilsmeier reactions of tertiary alcohols,
Diels–Alder reactions of 3-siloxy-1-aza-1,3-buta-
dienes and 6-alkyl-3,5-dichloro-2H-1,4-oxazin-2-
One-pot multicomponent coupling reactions (MCRs),
where several organic moieties are coupled in one
step, for carbon-carbon and carbon–heteroatom bond
formation is an attractive synthetic strategy for the
synthesis of small–molecule libraries with several
6
ones with different types of acetylenic compounds,
Ni/Ru-catalysed cycloadditions of alkynes and
7
nitriles, [4 + 2] cycloadditions of oximinosul-
8
fonates, reaction of imines with enamines or car-
1
9
degrees of structural diversities. The pyridine moiety
bonyl compounds, condensation of α,β-unsaturated
10
has been found in a wide variety of both naturally
occurring and synthetic bioactive compounds, and
esters or nitriles with thiols, and transformation of
11
ketene dithioacetals to pyridine derivatives.
2
are often with considerable complexity. The highly
A few MCR methods are also reported for synthesis
of diverse substituted pyridines, such as three-com-
substituted pyridine derivatives, like 2-amino-4-aryl-
3,5-dicyano-6-sulfanylpyridines have significant and
diverse medicinal utility. Essentially, these com-
pounds serve as high-potency agonists for the human
adenosine receptors and act as potential therapeutic
agents for the treatment of Creutzfeldt–Jacob dis-
ease, Parkinson’s disease, hypoxia, asthma, cancer,
ponent condensations of aldehyde, malononitrile and
12
thiol using various bases Et N, DABCO and basic
3
13
ionic liquid [bmIm]OH, and microwave irradiation
of aldehyde, β-ketoester and ammonium nitrate
14
using bentonite clay. One-pot, three-component
condensation of aldehydes, o-picolylamines and iso-
3
kidney disease and prion disease. In addition, they
cyanides produced the 1H-imidazol-4-yl-pyridines
15
serve as potassium channel openers with applica-
tions in treating urinary incontinence and exhibit
anti-bacterial, anti-biofilm and anti-infective proper-
in the presence of Lewis acid in methanol. Re-
cently Zhu et al reported the one-pot MCRs of aro-
matic aldehydes, 3-cyanoacetyl indoles and ammo-
nium acetate under microwave irradiation in the
4
ties.
16
Thus, the synthesis of highly substituted pyridine
derivatives has attracted much attension, and a num-
ber of methods have been developed to prepare
these compounds using a variety of protocols. Those
synthesis of bis(3′-indolyl)pyridine derivatives.
Nanocrystalline metal oxides have found excel-
lent applications as active adsorbents for gases, for
17
destruction of hazardous chemicals, and as cata-
18
lysts for various organic transformations. Their
*For correspondence
high reactivity is due to high surface areas combined
63

64
M Lakshmi Kantam et al
with unusually reactive morphologies. In continua- pressure to afford the crude product, which after
tion of our work on the application of nanomaterials chromatography on silica gel (60–120 mesh) using
in organic methodologies, here we report an effect- hexane/ethyl acetate in varying proportions as eluent
tive three-component condensation of aldehydes, afforded the respective pyridine or 1,4-dihydro-
malononitrile and thiols to afford 2-amino-4-aryl- pyridine. The products were characterized on the
3,5-dicyano-6-sulfanylpyridines P and the corre- basis of spectral data and the data of known pro-
sponding 1,4-dihydropyridines DP in moderate to ducts were also compared with the literature
12,13
high yields by using nanocrystalline magnesium oxide data.
The physical and spectral data of the new
(NAP-MgO) catalyst (schemes 1 and 2).
products are given below.
2.2a 2-Amino-4-furan-2-yl-6-phenylsulfanyl-pyri-
dine-3,5-dicarbonitrile (P9): Yellow solid; Melt-
ing point 190–192°C; IR (KBr): 3410, 3319, 3215,
2213, 1626, 1578, 1538, 1515, 1477, 1265, 749,
2. Experimental
2.1 General remarks
–1
1
687 cm ; H NMR (DMSO-d , 200 MHz) δ 6⋅71 (t,
6
Nanocrystalline MgO samples were obtained from
NanoScale Materials Inc., (formally Nantek, Inc.)
Manhattan, Kansas, USA. All catalysts were cal-
cined at 400°C for 4 h before use. All chemicals
were purchased from Aldrich Chemicals or S.D Fine
Chemicals Pvt. Ltd. India, and used as received.
ACME silica gel (60–120 mesh) was used for col-
umn chromatography, while thin layer chromatogra-
phy was performed on Merck make precoated silica
J = 3⋅8 Hz, 1H), 6⋅91 (s, br, 2H), 7⋅43–7⋅58 (m, 6H),
13
7⋅82 (s, 1H); C NMR (DMSO-d , 75 MHz) δ 82⋅7,
6
89⋅4, 112⋅8, 115⋅5, 115⋅6, 116⋅4, 127⋅1, 129⋅4,
129⋅6, 134⋅8, 143⋅9, 145⋅0, 146⋅5, 160⋅2, 167⋅3;
Mass (ESI): m/z 341 (M + Na) ; HRMS (ESI): Anal.
+
Calcd. for C H N ONaS: 341⋅0473; Found:
17 10
4
341⋅0487.
gel 60-F plates. Melting points were measured in
254
2.2b 2-Amino-4-phenyl-6-para-tolylsulfanyl-pyri-
dine-3,5-dicarbonitrile (P10): Colourless solid;
Melting point 246–249°C; IR (KBr): 3450, 3322,
3208, 2214, 1618, 1547, 1524, 1490, 1264,
open capillary tubes and are uncorrected. The IR
spectra of all compounds were recorded with a
NEXUS 670 FTIR spectrometer (Necolet Corpora-
tion Ltd, USA) using KBr pellet method. The IR
–1
1
808, 704 cm ; H NMR (DMSO-d , 200 MHz) δ
6
–1
values are reported in reciprocal centimeters (cm ).
2⋅43 (s, 3H), 6⋅58 (s, br, 2H), 7⋅24 (d, J = 8⋅2 Hz,
1
13
The H, C NMR spectra were recorded in DMSO-
with a Varian-Gemini 200 MHz or Bruker-
2H), 7⋅43 (d, J = 8⋅2 Hz, 2H), 7⋅51–7⋅58 (m, 5H);
13
d
C NMR (DMSO-d , 75 MHz) δ 20⋅8, 86⋅9, 93⋅1,
6
6
Avance 300 MHz spectrometer. Chemical shifts (δ)
are reported in parts per million (ppm), using TMS
(δ = 0) as an internal standard. The mass spectra
were recorded with a QSTAR XL high resolution
mass spectrometer (Applied Biosystems, Foster city,
USA).
114⋅9, 115⋅2, 123⋅4, 128⋅3, 128⋅6, 130⋅0, 130⋅2,
133⋅9, 134⋅8, 139⋅5, 158⋅5, 159⋅6, 166⋅5; Mass
(ESI): m/z 365 (M + Na) ; HRMS (ESI): Anal.
+
Calcd. for C H N NaS: 365⋅0836; Found:
20 14
4
365.0848.
2.2c 2-Amino-4-(4-methoxy-phenyl)-6-para-tolylsul-
fanyl-pyridine-3,5-dicarbonitrile (P11): Pale yellow
solid; Melting point 230–233°C; IR (KBr) ν 3463,
3323, 3215, 2221, 1632, 1603, 1545, 1508, 1258,
2.2 Typical procedure for the synthesis of
pyridines and 1,4-dihydropyridines
–1
1
To a stirred solution of the aldehyde (1⋅0 mmol) and
malononitrile (2⋅1 mmol) in 5 ml of ethanol, was
added NAP–MgO (0⋅1 g) at room temperature. The
resulting mixture was heated to 50°C, the thiol
(1⋅1 mmol) was added and the reaction mixture was
refluxed. After completion of the reaction (moni-
tored by TLC), the mixture was brought to room
temperature, centrifuged to separate the catalyst and
the catalyst was washed with ethyl acetate (3 × 5 mL).
The centrifugate was concentrated under reduced
1179, 1028, 811 cm ;
H
NMR (DMSO-d ,
6
200 MHz) δ 2⋅38 (s, 3H), 3⋅85 (s, 3H), 6⋅74 (s, br,
2H), 7⋅0 (d, J = 7⋅5 Hz, 2H), 7⋅19 (d, J = 8⋅2 Hz,
2H), 7⋅37 (d, J = 7⋅5 Hz, 2H), 7⋅43 (d, J = 8⋅2 Hz,
13
2H); C NMR (DMSO-d , 75 MHz) δ 20⋅9, 55⋅3,
6
86⋅8, 93⋅2, 113⋅8, 114⋅1, 115⋅3, 115⋅5, 123⋅5, 125⋅8,
128⋅1, 130⋅1, 130⋅2, 131⋅3, 134⋅9, 139⋅5, 158⋅3,
159⋅8, 160⋅8, 166⋅6; Mass (ESI): m/z 395 (M + Na) ;
HRMS (ESI): Anal. Calcd. for C H N ONaS:
+
21 16
4
395⋅0942; Found: 395⋅0944.

Synthesis of highly substituted pyridines
65
2.2d 2-Amino-6-(furan-2-ylmethylsulfanyl)-4-(4- 132⋅2, 135⋅0, 139⋅5, 153⋅9, 156⋅6, 159⋅5, 165⋅8;
methoxy-phenyl)-pyridine-3,5-dicarbonitrile (P15): Mass (ESI): m/z 425 (M + Na) ; HRMS (ESI): Anal.
+
Pale yellow solid; Melting point 217–218°C; IR Calcd. for C H N O NaS: 425⋅1048; Found:
22 18
4
2
(KBr): 3459, 3324, 3209, 2363, 2214, 1616, 1541, 425⋅1037.
1506, 1459, 1247, 1170, 1016, 826, 743 cm ; H
–1
1
NMR (DMSO-d , 200 MHz) δ 3⋅88 (s, 3H), 4⋅51 (s,
6
3. Results and discussion
2H), 6⋅29 (t, J = 2⋅2, 2⋅9 Hz, 1H), 6⋅44 (d,
J = 2⋅9 Hz, 1H), 7⋅04 (d, J = 8⋅8 Hz, 2H), 7⋅37–7⋅62
(m, 5H); C NMR (DMSO-d , 75 MHz) δ 25⋅9,
6
In order to understand the relationship between
structure and reactivity, various forms of magnesium
oxide crystals CM-MgO (commercial MgO, SSA:
13
55⋅2, 85⋅9, 93⋅4, 108⋅9, 110⋅7, 113⋅6, 114⋅0, 115⋅3,
125⋅7, 130⋅1, 142⋅7, 149⋅8, 158⋅1, 159⋅6, 160⋅7,
2
30 m /g), NA–MgO (NanoActive MgO, convention-
+
2
165⋅4; Mass (ESI): m/z 369 (M + Na) ; HRMS
ally prepared MgO, SSA: 250 m /g), NAP–MgO
(ESI): Anal. Calcd. for C H N ONaS: 369⋅0786;
19 14
4
(NanoActive Plus MgO, aerogel prepared MgO,
2
Found: 369⋅0776.
SSA: 590 m /g) were initially evaluated for the
three-component condensation of benzaldehyde,
malononitrile, and thiophenol at reflux temperature
of ethanol. All these MgO crystals catalysed the
reaction, but best result was obtained with NAP–
MgO (table 1).
2.2e 2-Amino-4-(2,6-dichloro-phenyl)-6-para-tolyl-
sulfanyl-1,4-dihydro-pyridine-3,5-dicarbonitrile
(DP3): Colourless solid; Melting point 313–
315°C; IR (KBr): 3443, 3353, 2204, 2168, 1643,
–1
1
1487, 1246, 1035, 811, 772 cm ; H NMR (DMSO-
In order to investigate the scope of the above op-
timized protocol, a variety of structurally different
aldehydes with different thiols and malononitrile
were employed for the three component condensa-
tion and the results are depicted in tables 2 and 3. As
summarized in table 2, for the synthesis of substi-
tuted pyridines, it was found that aromatic as well as
heterocyclic aldehydes underwent this reaction to
d , 200 MHz) δ 2⋅38 (s, 3H), 5⋅4 (s, br, 2H), 5⋅65 (s,
6
13
1H), 7⋅17–7⋅51 (m, 7H), 8⋅57 (s, br, 1H); C NMR
(DMSO-d , 75 MHz) δ 20⋅6, 34⋅8, 52⋅1, 86⋅9, 117⋅4,
6
119⋅7, 125⋅5, 128⋅6, 130⋅1, 130⋅4, 131⋅4, 135⋅1,
+
138⋅8, 143⋅4, 151⋅4; Mass (ESI): m/z 435 (M + Na) ;
HRMS (ESI): Anal. Calcd. for C H N NaSCl :
20 14
4
2
435⋅0213; Found: 435⋅0226.
2.2f 2-Amino-4-(2-chloro-6-fluoro-phenyl)-6-para-
tolylsulfanyl-1,4-dihydro-pyridine-3,5-dicarbonitrile
(DP6): Yellow solid; Melting point 277–279°C;
IR (KBr) ν 3465, 3362, 2205, 2169, 1643, 1599,
Table 1. One-pot synthesis of 2-amino-4-phenyl-6-
phenylsulfanyl-pyridine-3,5-dicarbonitrile P1 with vari-
a
ous catalysts .
–1
1
b
1488, 1449, 1243, 892, 778 cm ; H NMR (DMSO-
Entry
Catalyst
Time (h)
Yield (%)
d , 200 MHz) δ 2⋅36 (s, 3H), 5⋅22 (d, J = 2⋅1 Hz,
6
1H), 5⋅4 (s, br, 2H), 6⋅98–7⋅53 (m, 7H), 8⋅65 (s, br,
1H); C NMR (DMSO-d , 75 MHz) δ 20⋅6, 35⋅5,
6
c
c
1
2
3
4
5
NAP–MgO
NA–MgO
CM–MgO
Sil–NAP–MgO
None
2, 2
64, 58
4
9
59
55
50
–
13
52⋅4, 87⋅4, 115⋅2, 115⋅5, 117⋅6, 119⋅9, 126⋅1, 130⋅4,
130⋅8, 138⋅5, 142⋅9, 151⋅1; Mass (ESI): m/z 419
(M + Na) ; HRMS (ESI): Anal. Calcd. for C H
4
12
+
a
20 14
Reaction
conditions:
Benzaldehyde
(1⋅0 mmol),
N FNaSCl: 419⋅0509; Found: 419⋅0518.
4
malononitrile (2⋅1 mmol), thiophenol (1⋅1 mmol), catalyst
(0⋅1 g), ethanol (5 mL) at reflux temperature
Isolated yield; Fourth cycle
b
c
2.2g 2-Amino-4-(2,6-dimethoxy-phenyl)-6-para-
tolylsulfanyl-pyridine-3,5-dicarbonitrile
(P17):
Colourless solid; Melting point 202–203°C; IR
(KBr) ν 3440, 3343, 3220, 2212, 2180, 1630, 1593,
–1
1
1541, 1465, 1253, 1106, 1021, 768 cm ; H NMR
(DMSO-d , 200 MHz) δ 2⋅42 (s, 3H), 3⋅85 (s, 6H),
6
6⋅62 (s, br, 2H), 6⋅7 (d, J = 8⋅8 Hz, 2H), 7⋅24 (d,
J = 8⋅1 Hz, 2H), 7⋅45 (d, J = 8⋅1 Hz, 2H), 7⋅66 (s,
13
1H); C NMR (DMSO-d , 75 MHz) δ 20⋅8, 56⋅0,
6
88⋅8, 94⋅8, 104⋅5, 110⋅8, 114⋅7, 114⋅9, 123⋅2, 130⋅0,
Scheme 1. One-pot synthesis of substituted pyridines
catalysed by NAP–MgO.

66
M Lakshmi Kantam et al
Table 2. One-pot synthesis of substituted pyridines catalysed by NAP–MgO .
a
b
c
Entry
Ar
R
Time (h)
Product P
Yield (%)
1.
2.
3.
4.
5.
6.
7.
C H
6
C H
6
2
6
6
2
2
7
2
P1
P2
P3
P4
P5
P6
P7
64
61
59
52
49
64
50
5
5
5
5
5
5
5
5
4-MeO–C H
6
C H
6
4
4-Me–C H
6
C H
6
4
4-NO –C H
2 6
C H
6
4
4-Cl–C H
6
C H
6
4
4-OH–C H
6
C H
6
4
4-HOOC–C H
6
C H
6
4
8.
9.
C H
6
9
4
P8
P9
48
69
5
C H
6
5
10.
11.
12.
13.
14.
C H
6
4-Me–C H
6
4
8
5
4
7
P10
P11
P12
P13
P14
65
59
50
44
41
5
4
4
4-MeO–C H
6
4-Me–C H
6
4
C H
6
4-Cl–C H
5
5
6
4
2
2
C H
6
C H –CH
6 5
4-Me-C H
6
C H –CH
6 5
4
15.
4-MeO–C H
6
8
6
P15
P16
56
52
4
16.
4-Cl–C H
4
4
a
Reaction conditions: Aldehyde (1 mmol), malononitrile (2⋅1 mmol), thiophenol (1⋅1 mmol),
NAP–MgO (0⋅1 g), ethanol (5 mL) at reflux temperature
All the products were characterized by IR, H-NMR, C-NMR and mass spectroscopy
b
1
13
c
Isolated yield
a
Table 3. One-pot synthesis of substituted 1,4-dihydropyridines catalysed by NAP–MgO .
b
c
Entry
Ar
R
Time (h)
Product DP
Yield (%)
1.
2.
3.
2,6-Cl–C H
6
C H
6 5
5
4
4
DP1
DP2
DP3
87
80
84
3
3
3
2,6-Cl–C H
6
4-Cl-C H
6 4
2,6-Cl–C H
6
4-Me-C H
6 4
4.
2,6-Cl–C H
6
3
DP4
71
3
5.
6.
a
2-Cl-6-F-C H
6
C H
6 5
2
2
DP5
DP5
69
85
3
3
2-Cl-6-F-C H
6
4-Me-C H
6 4
Reaction conditions: Aldehyde (1 mmol), malononitrile (2⋅1 mmol), thiophenol (1⋅1 mmol),
NAP–MgO (0⋅1 g), ethanol (5 mL) at reflux temperature
All the products were characterized by IR, H-NMR, C-NMR and mass spectroscopy
b
1
13
c
Isolated yield
Scheme 2. One-pot synthesis of substituted 1,4-dihydropyridines
catalysed by NAP–MgO.

Synthesis of highly substituted pyridines
67
Scheme 3. One-pot synthesis of substituted pyridine P17 catalysed by NAP–
MgO.
afford their corresponding pyridine products in When the reaction was conducted with ethyl
moderate yields. The substrates bearing electron- cyanoacetate, benzaldehyde and thiophenol, only
donating (methyl, methoxy, methylenedioxy, 6% of the pyridine derivative was isolated. How-
hydroxy) or electron-withdrawing (nitro, carboxy, ever, there was no reaction with phenyl acetonitrile.
chloro) groups on the aromatic ring showed similar
It is noteworthy that there was no reaction without
results. Using furfural, malononitrile and thiophenol NAP–MgO catalyst (table 1, entry 5), which indi-
the pyridine derivative P9 (table 2, entry 9) was ob- cated that the catalyst is essential for the reaction.
tained in good yield. In contrast to the findings of The proposed mechanism is, in the first step of this
12
2–
–
Evdokimov et al, with aliphatic aldehydes, uniden- reaction, malononitrile is activated by O /O (Lewis
2+
+
tified constituents were isolated instead of the pyri- base) and aldehyde is activated by Mg /Mg (Lewis
13
dine product. Whereas, aliphatic cyclohexanethiol acid) of NAP–MgO. This involves the Knoevenagel
with 4-chlorobenzaldehyde gave the corresponding reaction which forms the corresponding Knoevena-
pyridine P16 (table 2, entry 16) in 52% of isolated gel product I (scheme 4). The second molecule of
yield. The other thiols such as 4-methyl benzene malononitrile then undergoes Michael addition to I,
2+
+
thiol, 4-chloro benzene thiol and furyl methanethiol simultaneously thiol activation by Mg /Mg of
reacted with different aromatic aldehydes to afford NAP–MgO, and the thiolate addition to CN of the
their corresponding pyridine derivatives in good adduct. Then cyclization takes place to form 1,4-
yields (table 2, entries 10–12 and 15), and with dihydropyridine which upon aromatization and
,
benzylthiol afforded the pyridine product in moder- aerobic oxidation under the reaction conditions,
13
ate yields (table 2, entries 13 and 14).
leads to pyridine product. Presumably, the reac-
When o,o′-disubstituted aldehydes were used in tions of o,o′-dihalo substituted aldehydes were
this process, 1,4-dihydropyridines were obtained in restricted to 1,4-dihydropyridines only, as further
high yields (table 3). The difference in the product aromatization did not occur, possibly, this is due to
profile may be due to steric hinderance of o,o′- steric hinderance at the 4-position by two ortho sub-
12,13
12,13
disubstituted biaryl systems.
In this system, 2,6- stituents at the aromatic ring.
dichloro-benzaldehyde and 2-Cl,6-F-benzaldehyde
To understand the relationship between structure
was combined with various thiols to afford 1,4- and reactivity of the catalyst in this three-component
dihydropyridines DP1–DP6 in good to high yields. reaction, it is important to know the structure and
In contrast, 2,6-dimethoxy benzaldehyde gave the nature of the reactive sites of NAP–MgO. The cata-
substituted pyridine P17 instead of the predicted 1,4- lyst NAP–MgO has a single crystallite, three-
dihydropyridine (scheme 3). This may be due to the dimensional polyhedral structure, with high surface
difference in the electronic and steric properties of concentrations of edges/corners and various exposed
2,6-dimethoxy benzaldehyde compared to 2,6-dihalo crystal planes (such as 002, 001, 111). This leads to
aldehydes and also the possibility of hydrogen bond- inherently high surface reactivity per unit area.
ing between halogens of 2,6-dihalo aldehydes and Besides this, the NAP–MgO has Lewis acid sites
2+
2–
–
hydrogen of pyridine ring.
Mg , Lewis basic sites O and O , lattice-bound
We also explored different active methylene group and isolated Bronsted hydroxyls and anionic and
19
containing nitriles such as ethyl cyanoacetate and 2- cationic vacancies. Thus, NAP–MgO displays the
phenyl acetonitrile for the synthesis of pyridines. highest activity compared to NA–MgO and CM–

68
M Lakshmi Kantam et al
Scheme 4. The plausible mechanism for one-pot synthesis of substituted pyri-
dines P and dihydropyridines DP catalysed by NAP–MgO.
MgO. Generally, this three-component reaction is washed with ethyl acetate for three times. The
12
known to be driven by base catalysts, and accord- recovered catalyst was activated at 250°C for 1 h
ingly, the surface –OH and O sites of these oxide under nitrogen atmosphere, before reuse.
2–
crystals are expected to trigger these reactions. The
19
poorer result with the Sil–NAP–MgO devoid of
4. Conclusion
free –OH, was established the role of –OH (table 1,
entry 4). Although both NAP–MgO and NA–MgO
In conclusion, we have demonstrated that nanocrys-
possess defined shapes and the same average con-
talline MgO is an effective catalyst for the MCRs of
centrations of surface –OH groups, a possible
structurally diverse aldehydes with various thiols
rationale for this higher reactivity towards pyridines
and malononitrile, resulting in the formation of
by the NAP–MgO is that the presence of more sur-
substituted pyridines and 1,4-dihydropyridines in
face Lewis acid sites (20%), along with –OH groups
moderate to high yields. The catalyst can be recove-
present on the edge and corner sites on the NAP–
red, and reused atleast up to four cycles for the syn-
MgO, which are stretched in three-dimensional
thesis of pyridine derivatives.
space, are therefore more isolated and accessible to
the reactants. Thus, NAP–MgO displays highest ac-
Acknowledgements
tivity compared to NA–MgO and CM–MgO. This
three-component reaction proceeds via dual activa-
K M thanks Council of Scientific and Industrial
tion of substrates by NAP–MgO. The Lewis base
Research (CSIR), New Delhi, India for the award of
2–
–
moiety (O /O ) of the catalyst activates the
his Senior Research Fellowship.
2+
+
malononitrile and the Lewis acid moiety (Mg /Mg )
20
activates the aldehyde and thiol (scheme 4).
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