Tungsten anchored onto functionalized SBA-15: An efficient catalyst for diastereoselective synthesis of 2-azapyrrolizidine alkaloid scaffolds

Article abstract of DOI:10.1039/c9ra02825k

We used a novel hybrid catalyst in chemo-, regio-, and diastereoselective multi-component reactions (MCR) for the synthesis of the 2-aza analogue of pyrrolizidine and spirooxindole-2-azapyrrolizidine derivatives. The nanocatalyst, W(iv)/NNBIA-SBA-15 [wher

Full text of DOI:10.1039/c9ra02825k

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Tungsten anchored onto functionalized SBA-15: an
efficient catalyst for diastereoselective synthesis of
2-azapyrrolizidine alkaloid scaffolds†
Cite this: RSC Adv., 2019, 9, 19662
*
Javad Safaei-Ghomi
and Atefeh Bakhtiari
We used a novel hybrid catalyst in chemo-, regio-, and diastereoselective multi-component reactions
(MCR) for the synthesis of the 2-aza analogue of pyrrolizidine and spirooxindole-2-azapyrrolizidine
derivatives. The nanocatalyst, W(IV)/NNBIA–SBA-15 [where NNBIA
¼
N,N0-(ethane-1,2-diyl)bis(2-
aminobenzamide)] was synthesized by covalent grafting on chloro-functionalized SBA-15. The synthesis
process was followed by the anchoring of WCl6 to catch the desired catalyst. The quality of the catalyst
was assessed using different analytical techniques such as X-ray diffraction spectroscopy (XRD), Fourier-
transform infrared spectroscopy (FT-IR), N2 adsorption analysis, transmission electron microscopy (TEM),
field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX),
ammonia Temperature Programmed Desorption (TPD), X-Ray photoelectron spectroscopy (XPS) and
thermogravimetric, differential thermal analysis (TGA-DTA). The catalyst, W(IV)/NNBIA–SBA-15, with high
catalytic performance is a good candidate for the diastereoselective synthesis of 2-azapyrrolizidine
alkaloid scaffolds. The catalyst could be recovered for reuse without noticeable loss of activity.
Received 14th April 2019
Accepted 3rd June 2019
DOI: 10.1039/c9ra02825k
rsc.li/rsc-advances
One of the most important classes of biological compounds
is hydantoins.13–15 The presence of three disparate nucleophilic
1. Introduction
centers in hydantoin provides the ability to synthesize many
biologically active molecules from several alternative cyclization
pathways.16 Pyrrolizidine alkaloids consisting of two fused ve-
member carbon rings with a nitrogen atom at one bridgehead
belong to the aza-heterocyclic family.17 They are commonly used
in chemical biology and medicinal chemistry due to their
medicinal properties.18,19 The presence of a nitrogen-substituted
carbon in the stereogenic center of pyrrolizidine alkaloids
increases their biological properties. Some of their derivatives
such as retronecine,20 heliotridine,21 and platynecine22 show
anti-tumoural, anti-microbial, and anti-viral effects. In previous
reports, conventional organic catalysts such as NEt3 (ref. 23)
and piperidine16,24 were employed for synthesizing 2-azapyrro-
lizidine alkaloid scaffolds.
Tungsten is a transition metal of Group VIb of the periodic
table of elements, and it has attracted a great deal of attention
due to its extraordinary properties.25 The use of tungsten in new
applications has made it useful as an essential commodity in
recent years.26 Tungsten based catalysts with unique functional
properties have been widely used for various applications, such
as the selective oxidation of unsaturated compounds,27 metath-
esis and isomerization of alkenes28 and the dehydrogenation of
alcohols.29 They are most useful for addition reactions to olenic
double bonds.30 Recently, researchers have attempted to insert
tungsten into siliceous mesoporous molecular sieves (e.g., silica,
M41S, and SBA-n)31–33 by various methods such as graing,34
cogelation,35 impregnation36 or insertion.37 The diverse
Chemical researchers are focused on the synthesis of func-
tionalized nitrogen and oxygen-containing organic compounds
that have potential medicinal and biological activities.1,2
Diversity-oriented synthesis (DOS) is one of the strategies used
to provide synthetic methods for the efficient combination of
regiochemically and functionally diverse simple molecules.3–5
DOS is especially useful for those structures based on natural
products or drug-like molecules.6,7 The aim of DOS is to achieve
simultaneous, deliberate, and impressive syntheses of struc-
turally diverse compounds such as drug molecules or natural
products.3–5,8 MCRs9 can be placed in the class of DOS chemistry
due to green characteristics, straightforward reaction designs,
high degrees of atom economy, lower costs and environmen-
tally friendliness.10 The use of water in chemical reactions has
many advantages in the eld of green chemistry, such as
modifying the reactivity and selectivity of the reaction.11
Spirocyclic structures that contain one sp3 carbon atom
common to two rings have many biological properties. They
have attracted the considerable attention of organic chemists
because of being in natural ingredients.12
Department of Organic Chemistry, Faculty of Chemistry, University of Kashan, P. O.
Box 87317-51167, Kashan, I. R. Iran. E-mail: safaei@kashanu.ac.ir; Fax: +98 31
55552935; Tel: +98 31 55912385
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c9ra02825k
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compositions of incorporated tungsten into siliceous meso- of pyrrolizidine and spirooxindole-2-azapyrrolizidine deriva-
porous materials have resulted in improved catalytic activities. tives. The nanocatalyst, W(IV)/NNBIA–SBA-15, was prepared by
Considerable attention has been paid to designing hetero- applying simple and cost-effective materials and also it was
geneous catalysts, due to their advantages such as easy sepa- characterized as a new inorganic–organic hybrid catalyst. The
ration, easy recovery, and high reusability. The surface support one-pot reactions of aldehyde or isatin (1 mmol), malononitrile
has an inuential effect on the behavior of heterogeneous (1 mmol), and hydantoin (1 mmol) were catalyzed by W(IV)/
catalysts. Several solid supports have been introduced such as NNBIA–SBA-15 in water (Scheme 1).
polymer resins, silica, alumina, silica-coated magnetic particles,
and mesoporous molecular sieves. The fully ordered structure
of mesoporous silica leads to the generation of a framework
with regular porosity, so ligands could be immobilized well on
2. Results and discussion
2.1. Structural analysis of W(IV)/NNBIA–SBA-15
A small angle X-ray diffraction method was used to monitor the
effect of incorporation of the ligand, NNBIA, and the metal on
the framework of SBA-15 (Fig. 1). The patterns for both of SBA-
15 and W(IV)/NNBIA–SBA-15 show an intense diffraction peak
(100) which references to the mesostructure with a remarkable
degree of long-range ordering. The observed intensities of the
two secondary peaks corresponding to (110) and (200) reec-
tions are weak and they are attributed to the 2D-hexagonal
planes of the mesoporous structure.56,57 The XRD pattern of
W(IV)/NNBIA–SBA-15 indicates a striking effect by loading of the
ligand and the metal. The width and intensity of the diffraction
peak (100) become broader and weaker respectively, and also it
shis to lower 2q values than the XRD pattern of pure SBA-15.
Partial blockage of the available pores of the anchored catalyst
decreased the long-range order of SBA-15.58 It can be inferred
from the above results that the framework of SBA-15 remains
perfect aer incorporation of W(IV)-NNBIA.
The surface and structure properties of pure SBA-15 and
W(IV)/NNBIA–SBA-15 were evaluated by N2 adsorption–desorp-
tion isotherms analysis and BJH pore size distributions (Fig. 2).
Both of them show a type IV isotherm with an H1 hysteresis
loop which is in agreement with the typical mesostructure. The
steep adsorption step at 0.4 to 0.8 P/Po corresponds to the
capillary condensation of nitrogen in uniform pores. The
it. Because of the advantages of mesoporous silica, it could be
vastly employed in separation, catalysis, gas storage, drug
delivery, and biomolecule applications. Since the development
of ordered mesoporous silicas,38,39 SBA-15 materials developed
by Zhao and Stucky40,41 serve in many elds due to their inter-
esting textural properties such as their appreciable thermal and
hydrothermal stabilities, large pore volumes, uniform-sized
pores (in the range 4–30 nm) and high specic surface areas
(above 1000 m2 gꢀ1).42–48 The creation of organic–inorganic
hybrid catalysts is the best methodology to overcome a lack of
functionality by using a variety of organic functional groups.49–51
The unique abilities of organic–inorganic hybrid materials
make these systems highly attractive candidates for a range of
applications including recyclable catalysts, drug delivery,
biotechnology, biomedicine etc.52–54 There are a number of
methods for the synthesis of hybrids catalyst. Among them,
stable attachment and less leaching55 are observed post-
-synthetically. The available ligand precursors can be used for
multifunctional integration of SBA-15.
We are interested in the development of our research to
prepare more effective catalysts to synthesize a 2-aza analogue
Scheme 1 Synthesis of the 2-aza analogue of pyrrolizidine and spi-
rooxindole-2-azapyrrolizidine derivatives.
Fig. 1 The XRD patterns of SBA-15 and W(IV)/NNBIA–SBA-15.
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Table 1 Structural and textural parameters of SBA-15, and W(IV)/
NNBIA–SBA-15
Sample
SBETa [cm2 gꢀ1
]
Dpb [nm]
VP [cm3 gꢀ1
c
]
SBA-15
W(IV)/NNBIA–SBA-15
758.68
182.29
9.40
8.06
0.737
0.392
a
b
c
SBET ¼ surface area. Dp ¼ average pore width. Vp ¼ total pore
volume.
spectrum (Fig. 3). The amount of carbon, nitrogen, oxygen,
silicon, chlorine and tungsten in W(IV)/NNBIA–SBA-15 were
calculated to be 30.63, 15.06, 30.44, 9.89, 8.39, 5.59 (wt%),
respectively. The EDS mapping analysis suggested a highly
uniform dispersion of the ligand, NNBIA and tungsten on SBA-
15.
The FESEM images of the SBA-15 and W(IV)/NNBIA–SBA-15
are shown in Fig. 4a and b. The FESEM images show that
both of them have good structural integrity and morphology.
The surface morphology was not changed by functionalization.
The evaluation of the used catalyst structure by FESEM
evidences that the morphology of the catalyst remained
unchanged aer the 5th cycle (Fig. 4c). This is the feasible
reason for the extreme stability of the catalyst. The presence of
a 2D hexagonal network was conrmed by the TEM image of
a W(IV)/NNBIA–SBA-15 sample (Fig. 4d). The TEM image shows
highly dispersed W(IV)/NNBIA both inside and outside the
channels of SBA-15.
FT-IR spectroscopy is an effective technique to conrm and
identify the structure of a catalyst. Fig. 5 shows the FT-IR
spectra at all stages of the process of creating the catalyst. The
peaks of the absorption bands associated with the formation of
a condensed silica network appear around 1077, 801, and
455 cmꢀ1. The peak at 1077 cmꢀ1 can be attributed to the
asymmetric stretching vibration peak of Si–O–Si groups. The
Fig.
2 N2 adsorption–desorption isotherms and BJH pore size
distributions of SBA-15, and W(IV)/NNBIA–SBA-15.
sharpness of the pore-lling step in the adsorption and
desorption curves is related to the uniformity of the mesopore
size distribution. Due to pore blocking effect, the functionali-
zation of SBA-15 not only shis the inection to a lower P/Po
range but also diminishes the sharpness of it.43 The reduction
in sharpness of the functionalized SBA-15 is due to less
uniformity in the mesopore size distribution. The above results
clearly indicate that the ordered mesoporous structure of SBA-
15 with a narrow pore size distributions remains well aer
immobilizing W(IV)/NNBIA. The BET surface area (758 m2 gꢀ1),
the average pore diameter (9.4 nm) and the total pore volume
(0.737 cm3 gꢀ1) of SBA-15 were recorded (Table 1). The textural
parameters of W(IV)/NNBIA–SBA-15 are changed by the cooper-
ation of the ligand and the metal. The data for the surface area,
average pore width, and total pore volume for W(IV)/NNBIA–
SBA-15 are presented in Table 1. The results show that W(IV) is
placed mainly inside the channels of the modied SBA-15
materials.
The incorporation efficiency and contents of the ligand and
metal in the mesoporous SBA-15 were analysed using an EDS
Fig. 3 EDS spectrum of W(IV)/NNBIA–SBA-15.
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Fig. 4 FESEM images of (A) SBA-15, (B) W(IV)/NNBIA–SBA-15 and (C)
the used W(IV)/NNBIA–SBA-15 and (D) A TEM image of W(IV)/NNBIA–
SBA-15.
peaks at 3439 and 1632 cmꢀ1 are due to the stretching and
bending vibrations of the surface hydroxyl groups, respec-
tively.48 The spectrum of chloro-functionalized SBA-15 shows
a peak at 3114 cmꢀ1 related to a C–H stretching vibration within
the propyl group, and the peak at 709 cmꢀ1 corresponds to the
C–Cl bonds. The FT-IR spectrum of the ligand, NNBIA, shows
three strong absorption peaks due to the carbonyl groups and
aromatic rings at 1548, 1580 and 1629 cmꢀ1. Three other peaks
at 3285, 3368 and 3474 cmꢀ1 could be assigned to the N–H
bonds of the ligand. The absorption peaks of the carbonyl
groups are shied toward low frequencies with the immobili-
zation of the ligand, NNBIA, over the Cl–SBA-15. Due to ligand
binding, the peak of the N–H bond was observed at 3319 cmꢀ1
and the C–Cl stretch disappeared. Coordination of WCl6 to
NNBIA–SBA-15 led to the disappearance of a sharp absorption
peak at 3319 cmꢀ1 that could be attributed to the removal of the
N–H bonds. A wide peak at 3442 cmꢀ1 could be attributed to
some unreacted hydroxyl groups remaining on the surface of
SBA-15. The combination of the organic ligand with the W is
conrmed by these results. The reused catalyst aer ve runs
had no obvious changes in structure, based on the results of the
FT-IR spectrum when compared with the spectrum of the fresh
catalyst.
Fig. 5 FT-IR spectra of (a) the ligand, NNBIA, (b) calcined SBA-15, (c)
chlorofunctionalized SBA-15, (d) NNBIA–SBA-15, (e) fresh W(IV)/
NNBIA–SBA-15 and (f) used W(IV)/NNBIA–SBA-15.
related to the loss of physically bound water and the break-up
of a hydrogen bonded network. The second region is from
ꢁ
ꢁ
ꢂ200 C to 800 C and is associated to the dihydroxylation of
OH groups. It can be evidently supported by one strong
exothermic peak in the same temperature range in the DTA
analysis. The TGA prole of W(IV)/NNBIA–SBA-15 shows
ꢁ
a weight loss of 36% in the temperature range of 350–600 C,
which is accompanied by a broad exothermic peak between
370 ꢁC and 750 ꢁC in the DTA curve. This is associated with
ligand desorption or decomposition. Based on these results,
the amount of active catalyst present on the heterogeneous SBA
support is 1.5 mmol. The decomposition of the W(IV)/NNBIA
complex is done at a high temperature, and that demon-
strates the high thermal stability of the complex. Consequently,
the results reported thus far indicate that W(IV)/NNBIA is
formed and principally located, inside the SBA-15 pore
channels.
The NH3-TPD prole of W(IV)/NNBIA–SBA-15 is shown in
Fig. 7. The acid sites are distributed in two temperature regions.
The second peak at about 450 ꢁC is sharper and wider than the
rst one at about 250 ꢁC. They could be attributed to weak acid
sites and medium-strong acid sites, respectively. The desorp-
tion peak at the low temperature of 250 ꢁC was observed due to
The thermal behaviors of SBA-15 and W(IV)/NNBIA–SBA-15
from 30 ꢁC to 800 ꢁC are represented in Fig. 6. The TGA
prole of the silica support exhibits two steps of weight loss.
ꢁ
The rst weight loss (ꢂ9%) is in the region from ꢂ150 C to
ꢁ
250 C and corresponds to a sharp visible exothermic peak in
the DTA analysis in the same temperature region. This is
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Fig. 7 NH3-TPD spectrum of W(IV)/NNBIA–SBA-15.
X-Ray photoelectron spectroscopy was applied to dene the
electronic state of the tungsten and the atomic concentration of
the catalyst. The XPS spectrum of the catalyst shows peaks
corresponding to Si, O, C 1s, N 1s, Cl 2s, Cl 2p, and W (Fig. 8F).
The W 4f spectrum shows that the tungsten is present as W4+
,
with W 4f5/2 and W 4f7/2 binding energies of 35 and 33.5 eV,
respectively, with an approximate intensity ratio of 3 : 4 (ref. 59)
(Fig. 8E). The Si 2s and Si 2p peaks are centered at 103 and
150 eV respectively and clearly show the presence of the SiO2
structure60 (Fig. 8D). Fig. 8C shows a peak at 285.0 eV for C 1s to
p*(C]C) and p*(C]N) orbitals.61 A broad peak extending from
396 to 403 eV is observed for all of the N contained within the
catalyst (Fig. 8B). The O 1s XPS spectrum shown in Fig. 8A
reveals a well-dened peak at 533.52 eV that could be attributed
to SiO2 (533 eV), C–O (531–532 eV) and C]O (533 eV). Infor-
mation on the atomic concentration of the W(IV)/NNBIA–SBA-
15, as obtained from XPS, is summarized in Table 2.
2.2. Catalytic tests
2.2.1. Comparison of the efficiency of W(IV)/NNBIA–SBA-15
and other catalysts. The merit of the W(IV)/NNBIA–SBA-15
nanocatalyst was investigated in an MCR reaction. The reac-
tion of isatin, malononitrile, and hydantoin was selected as
a model reaction and the results were summarized in Table 3.
Almost no corresponding product was obtained in the absence
of catalyst aer 48 h under reux or at 80 ꢁC in water. We
compared the efficiency of homogeneous catalysts such as
piperidine, triethylamine, L-proline, DABCO, and NH2–SBA-15
with W(IV)/NNBIA–SBA-15. The obtained results indicated that
the presence of the nanocatalyst, W(IV)/NNBIA–SBA-15, was
much more efficient than previously reported homogenous
basic catalysts (Table 3, entries 3–7). The adsorption of reac-
tants on the surface of the nanocatalyst support increased the
local concentration of reactants around the active sites of W(IV)/
NNBIA–SBA-15. The effect of functionalization was evaluated
using SBA-15 alone. The results indicated that SBA-15 alone was
almost inactive, which is probably due to the absence of active
sites (Table 3, entries 7 and 8). The effect of the metal was
Fig. 6 TGA and DTA curves of (A) SBA-15, and (B) W(IV)/NNBIA–SBA-
15 and (C) TGA curves of SBA-15 and W(IV)/NNBIA–SBA-15.
the physically adsorbed ammonia and weakly bonded
ammonia. The second-wide peak could be assigned to ammonia
on the medium-strong acid sites.
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Table 3 The effect of the different catalysts on the synthesis of 2-
azapyrrolizidine alkaloids
Entry
Catalysta
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
No catalyst (reux)
No catalyst
48
48
8
7
15
8
Trace
Trace
50
75
32
17
95
$20
40
50
Piperidine (20 mol%)
NEt3 (20 mol%)
L-Prolin (20 mol%)
DABCO (20 mol%)
W(IV)/NNBIA–SBA-15 (0.03 g)
SBA-15
3
18
18
12
NNBIA–SBA-15
WCl6
a
Reactions conditions: isatin (1 mmol), malononitrile (1 mmol), and
hydantoin (1 mmol) in water at 80 ꢁC. b Isolated yield.
The temperature had the greatest effect on the reaction
progress. A trace amount of product was yielded at room
temperature aer 48 h, and the results of the reux conditions
were not appropriate (Table 4, entries 6–8). The best results were
ꢁ
obtained at 80 C.
The inuence of the catalyst amount was studied under the
optimum conditions (Table 4, entries 8–10). An acceptable
reaction time and yield were obtained by loading 0.03 g of
catalyst, and no benet was observed with a greater catalyst
amount.
2.2.3. Synthesis of 2-azapyrrolizidine alkaloids derivatives
in the presence of W(IV)/NNBIA–SBA-15 under optimized
conditions. The crucial characteristics of the new organic–
inorganic catalyst, W(IV)/NNBIA–SBA-15, are chemical stability,
reusability, and non-toxicity. The efficiency of the catalyst was
tested for the synthesis of a broad range of 2-azapyrrolizidine
alkaloids. The methodology was explored by using various
carbonyl derivatives (1 mmol), malononitrile (1 mmol) and
hydantoin (1 mmol), under optimized conditions. In the pres-
ence of various isatin compounds, the desired products were
obtained in good yield and diastereoselectivity (Table 5).
Furthermore, the results of the scope of the reaction showed
that the reaction progressed well with different aldehydes with
electron donating and electron withdrawing groups substituted
(Table 6).
Fig. 8 XPS spectra of (A) O 1s, (B) N 1s, (C) C 1s, (D) Si 2p, (E) W 4f and
(F) W(IV)/NNBIA–SBA-15.
Table 2 Results of XPS elemental analysis in % for W(IV)/NNBIA–SBA-
15
Sample
O
N
C
Cl
Si
W
W(IV)/NNBIA–SBA-15 (%)
11.0
5.0
78.0
1.8
4.0
0.1
investigated. Based on the results, the absence of metal in the
catalyst decreased the yield and increased the time of the
reaction (Table 3, entries 7 and 9). WCl6 alone provided the
desired product in a 50% yield which points to the importance
of the presence of the support and the ligand (Table 3, entries 7
and 10).
2.2.2. Effect of solvent, temperature and catalyst amount
on the synthesis of 2-azapyrrolizidine alkaloids. The effect of
water and organic solvents such as EtOH, PhCH3, CH3CN, and
DMF were studied on the sequential one-pot reaction (Table 4,
entries 1–6). In the presence of polar solvents such as H2O and
EtOH, the product was synthesized in excellent yields, although
a gummy solid was obtained with EtOH. The best results were
obtained using water in terms of both yield and time. Thus we
kept this as the optimal solvent for the subsequent reactions.
2.3. Characterization of the products of the three
component reactions
High diastereoselectivity can be observed by using aldehydes to
produce only the trans diastereomer. The MCR reaction causes
the generation of a cis-fused 2-azapyrrolizidine. Actually, the
two hydrogens attached to the adjacent chiral carbon are trans.
In the presence of isatin, a highly strained spirooxindole with
a quaternary stereocenter was generated in only one diaste-
reomer of a racemic mixture. The regioselectivity of the reaction
can be rationalized by analysing the structure of hydantoin.
Scheme 2 shows that hydantoin can play either the role of a 1,3-
binucleophile when using the (CH2) and the (O) of the amide
moiety or the role of a 1,2-binucleophile when using the (CH2)
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Table 4 Optimization of solvent, temperature and catalyst amount for the synthesis of 2-azapyrrolizidine alkaloids
Catalyst amount
(g)
Entrya
Solvent
Temp. (ꢁC)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
CH3CN
CH3Ph
DMF
EtOH
EtOH–water
Water
Water
Water
Water
Water
Reux
Reux
Reux
Reux
Reux
Reux
r.t.
80
80
80
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.02
0.04
12
48
12
4
4
8
48
3
4
72
Trace
24
83
85
50
5
95
80
95
4
a
Reactions conditions: isatin (1 mmol), malononitrile (1 mmol), and hydantoin (1 mmol). b Isolated yield.
Table 5 Synthesis of spirooxindole-2-azapyrrolizidine derivatives
Table 6 Synthesis of 2-azapyrrolizidine derivatives
Isatin 1a–
g
Aldehyde
Entrya R1
R2
Product 4a–h Time (h) Yieldb (%) mp (ꢁC)
Entrya R1
R2
R3
R4 Product Time (h) Yieldb (%) mp (ꢁC)
1
2
3
4
5
6
7
8
H
Me
H
H
H
H
H
H
H
H
Cl
F
Br
I
4a
4b
4c
4d
4e
4f
3
4
4
5
5
5
6
5
95
85
80
79
90
85
78
90
260
280
300
304
318
291
340
271
1
2
3
4
5
6
7
8
H
H
H
OMe
H
H
H
Cl
H
H
H
H
H
NO2
OMe
Me
H
OMe
Br
H
Cl
H
H
H
H
H
H
H
H
4i
4j
3
3
1
6
95
95
92
50
74
85
96
54
260
260
275
245
271
265
281
265
4k
4l
4m
4n
4o
6
2
5
NO2
OMe 4h
4g
Cl 4p
a
Reactions conditions: isatin derivatives (1 mmol), malononitrile (1
a
mmol), and hydantoin (1 mmol). b Isolated yield.
Reactions conditions: aldehyde derivatives (1 mmol), malononitrile (1
mmol), and hydantoin (1 mmol). b Isolated yield.
and the adjacent (NH). Pyrano-spirooxindole (A) is the corre-
sponding product if hydantoin reacts as a 1,3-binucleophile and
product 4k is expected if hydantoin reacts as a 1,2-binucleo-
by coordination with the W(IV)/NNBIA–SBA-15. The nitrile is
coordinated to a tungsten site which is followed by a mecha-
1
nism involving
a
proton abstraction, and
a
stable
phile. Structure 4k was conrmed by H NMR spectroscopy. It
hydrido(enolato)-complex (A) is afforded.62 Then the Knoeve-
nagel condensations of (A) with carbonyl group derivatives are
carried out to produce the cyano olens (B1) and (C1). Depro-
tonations of the cyano olens (B1) and (C1) take place at the
amino groups distributed on the surface of W(IV)/NNBIA–SBA-15
to yield the nucleophiles. On the other hand, coordination of
the carbonyl groups of hydantoin to a tungsten site of the W(IV)/
NNBIA–SBA-15 activates the electrophile in close proximity to
the nucleophile. As the second step, a Michael addition occurs
to generate intermediates (B2) and (C2).63 They are held in close
indicates exchangeable protons at 11.67, 10.60 and 7.76 ppm
with a 1 : 1 : 2 ratio, that can be referenced to two types of (NH)
and an (NH2) respectively. In addition, the 1H NMR shows 1
proton for the one singlet at 5.11 ppm which is matched by the
structure of 4k.
2.4. A plausible mechanism for the preparation of 2-
azapyrrolizidine alkaloids
A plausible catalytic cycle for the present reaction is illustrated
in Scheme 3. The electrophilicity of malononitrile is increased
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electrophilicity of the reactants. The high surface area of the
SBA-15 is very important for the high turnover frequency of the
reaction. The role of water as the solvent was evaluated. Water
molecules form H-bonds with organic reactants that have
hydrogen bond acceptor sites, both in their initial states and in
their reaction transition states. H-bonding reduces the energy of
the frontier orbitals by decreasing interorbital repulsion and
electron density.64
2.5. Hot ltration test for the W(IV)/NNBIA–SBA-15 catalyst
We did a hot ltration test to prove that the organic moiety was
attached to SBA-15 by covalent bonding that leads to stable
attachment and less leaching. This test was carried out on the
model reaction in the presence of 0.03 g of W(IV)/NNBIA–SBA-15
at 80 ꢁC for 30 min. The reaction was continued for another
30 min in the absence of the catalyst and the yield of the
product did not improve. Based on the results, the heteroge-
neity, the leaching-resistant properties and the stability of the
W(IV)/NNBIA–SBA-15 catalyst have been conrmed.
Scheme 2 Investigation on the structure of hydantoin.
proximity to the W(IV)/NNBIA–SBA-15 through coordination of
the carbonyl groups of hydantoin to a tungsten site of the W(IV)/
NNBIA–SBA-15. Then, the reaction might follow either a 5-exo-
dig or 6-exo-dig pathway. However, the reactions are chemo-
selective and the corresponding products were achieved by 5-
exo-dig. The amino groups distributed on the surface of W(IV)/
NNBIA–SBA-15 provide a nucleophilic mechanism. Tungsten
sites at the surface of the nanocatalyst increase the
2.6. Reusability of the W(IV)/NNBIA–SBA-15 catalyst
The model reaction with isatin (1 mmol), malononitrile (1
mmol), and hydantoin (1 mmol) was also employed to examine
the reusability of the nanocatalyst, W(IV)/NNBIA–SBA-15. Aer
the accomplishment of the reaction, the catalyst was ltered
and washed with 5 mL hot ethanol (3 ꢃ 10 mL) and water (2 ꢃ 5
Scheme 3 The proposed mechanism for the synthesis of azapyrrolizidine alkaloids.
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1
3237, 2750, 2197, 1790, 1742, 1700, 1636, 1572; H NMR (400
MHz, DMSO-d6): d ¼ 11.057 (br, 1H, NH), 10.749 (br, 1H, NH),
7.831 (br, 2H, NH2), 7.568 (s, 1H), 7.333 (d, J ¼ 7.2 Hz, 1H), 6.882
(d, J ¼ 7.2 Hz, 1H), 5.168 (s, 1H, CH); C14H8ClN5O3: C, 51.12; H,
2.64; N, 21.32; found: C, 51.23; H, 2.34; N, 21.17; HR-MS m/z:
calcd for C14H8ClN5O3 [M + Na]+: 352.0213; found: 352.0216.
2.7.4 4d:
(trans-3,7a0)-50-amino-5-bromo-10,2,30-trioxo-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
azole]-60-carbonitrile. mp ¼ 304 ꢁC; IR (KBr, cmꢀ1): 3485, 3385,
1
3243, 3150, 2736, 2193, 1790, 1744, 1707, 1634; H NMR (400
MHz, DMSO-d6): d ¼ 12.45 (br, 1H, NH), 11.127 (br, 1H, NH),
7.728 (br, 2H, NH2), 7.708 (d, J ¼ 7.5 Hz, 1H), 7.288 (s, 1H), 6.865
(d, J ¼ 7.5 Hz, 1H), 5.150 (s, 1H, CH); anal. calcd for
C
14H8BrN5O3: C, 44.82; H, 2.13; N, 18.61; found: C, 44.70; H,
2.53; N, 18.83. HR-MS m/z: calcd for C14H8BrN5O3 [M + Na]+:
Fig. 9 Recyclability study of the nanocatalyst, W(IV)/NNBIA–SBA-15,
for the reaction of isatin (1 mmol), malononitrile (1 mmol) and
hydantoin (1 mmol) under optimized conditions.
395.9708; found: 395.9709.
2.7.5 4e:
(trans-3,7a0)-50-amino-5-uoro-10,2,30-trioxo-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
azole]-60-carbonitrile. mp ¼ 318 ꢁC; IR (KBr, cmꢀ1) ¼ 3378, 3200,
2186, 1794, 1712, 1662, 1601; 1H NMR (400 MHz, DMSO-d6): d ¼
11.697 (s, 1H, NH), 10.643 (s, 1H, NH), 7.83 (br, 2H, NH2), 7.44
(d, J ¼ 8.4, 1H), 7.16–7.11 (m, 1H), 6.88 (d, J ¼ 8.4, 1H), 5.16 (s,
1H, CH); anal. calcd for C14H8FN5O3: C, 53.68; H, 2.57; N, 22.36;
found: C, 53.52; H, 2.59; N, 22.42; HR-MS m/z: calcd for
mL) and reused in a new reaction. However, in the second run,
the conversion under similar conditions had a negligible
reduction due to the blockage of catalytic sites with the reac-
tants (Fig. 9). Aer the second run, the reused catalyst was
washed three times with 5 mL hot ethanol (3 ꢃ 10 mL) and
water (2 ꢃ 5 mL) to remove residual reactants and that resulted
in the restoration of activity of the catalyst. In the third run, the
reaction yield was improved by using the reused catalyst. Based
upon these results, it was found that the W(IV)/NNBIA complex
was strongly anchored on the mesoporous supports, and the
catalytic activity did not decrease.
C
14H8FN5O3 [M + Na]+: 336.0508; found: 336.0509.
2.7.6 4f:
(trans-3,7a0)-50-amino-5-iodo-10,2,30-trioxo-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
azole]-60-carbonitrile. mp ¼ 291 ꢁC; IR (KBr, cmꢀ1): 3375, 3346,
1
3258, 3204, 2192, 1798, 1743, 1712, 1660, 1623; H NMR (400
MHz, DMSO-d6): d ¼ 11.71 (s, 1H), 10.73 (s, 1H), 7.83 (br, s, 2H),
7.80 (d, J ¼ 1.6 Hz, 1H), 7.63 (q, J ¼ 8.4, 8.0 Hz, 1H), 5.18 (s, 1H);
anal. calcd for C14H8IN5O3: C, 39.91; H, 3.37; N, 21.42; found: C,
40.01; H, 3.38; N, 21.39. HR-MS m/z: calcd for C14H8IN5O3 [M +
Na]+: 443.9568; found: 443.9570.
2.7. Study of the spectral data of some representative 2-
azapyrrolizidine alkaloid scaffolds
2.7.1 4a: (trans-3,7a0)-50-amino-10,2,30-trioxo10,20,30,7a0-tet-
2.7.7 4g:
(trans-3,7a0)-50-amino-5-nitro-10,2,30-trioxo-
rahydro spiro[indoline-3,70-pyrrolo[1,2-c]imidazole]-60-carbon- 10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
itrile. mp ¼ 260–262 ꢁC; IR (KBr, cmꢀ1) ¼ 3372, 3341, 3252, azole]-60-carbonitrile. mp ¼ 340 ꢁC; IR (KBr, cmꢀ1) ¼ 3499, 3424,
1
1
3200, 2182, 1791, 1738, 1702, 1656, 1620; H NMR (400 MHz, 3302, 3195, 2200, 1807, 1785, 1751, 1735, 1722, 1650, 1628; H
DMSO-d6): d ¼ 11.680 (s, 1H, NH), 10.609 (s, 1H, NH), 7.775 NMR (400 MHz, DMSO-d6): d ¼ 11.648 (br, 1H, NH), 11.283 (br,
(br, s, 2H, NH2), 7.408 (d, J ¼ 8 Hz, 1H), 7.253 (t, J ¼ 8 Hz, 1H), 1H, NH), 8.440 (d, J ¼ 8 Hz, 1H), 8.20 (s, 1H), 7.640 (br s, NH2),
7.049 (t, J ¼ 8 Hz, 1H), 6.853 (d, J ¼ 8 Hz, 1H), 5.11 (s, 1H, CH); 7.066 (d, J ¼ 8.Hz, 1H), 5.437 (s, 1H, CH); anal. calcd for
anal. calcd for C14H9N5O3: C, 56.45; H, 3.07; N, 23.72; found: C,
C14H8N6O5: C, 49.41; H, 2.36; N, 24.69; found: C, 50.01; H,
56.99; H, 3.12; N, 23.78; HR-MS m/z: calcd for C14H9N5O3 [M + 2.48; N, 24.52. HR-MS m/z: calcd for C14H8N6O5 [M + Na]+:
Na]+: 318.0603; found: 318.0609.
363.0453; found: 363.0455.
2.7.2 4b:
(trans-3,7a0)-50-amino-1-methyl-10,2,30-trioxo-
2.7.8 4h:
(trans-3,7a0)-50-amino-5-methoxy-10,2,30-trioxo-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
azole]-60-carbonitrile. mp ¼ 280 ꢁC; IR (KBr, cmꢀ1): 3552, 3501, azole]-60-carbonitrile. mp ¼ 265 ꢁC; IR (KBr, cmꢀ1): 3377, 3325,
1
1
3210, 2928, 2187, 1790, 1742, 1688, 1648; H NMR (400 MHz, 3267, 2895, 2187, 1801, 1748, 1720, 1659, 1593; H NMR (400
DMSO-d6): d ¼ 11.04 (br, 1H, NH), 7.741 (br, 2H, NH2), 7.526 (d, MHz, DMSO-d6): d ¼ 11.67 (br, 1H, NH), 10.42 (br, 1H, NH), 7.76
J ¼ 7.5 Hz, 1H), 7.339 (t, J ¼ 7.5 Hz, 1H), 7.108 (t, J ¼ 7.5 Hz, 1H), (br, 2H, NH2), 7.10 (d, J ¼ 8.4 Hz, 1H), 6.84 (d, J ¼ 8.4, 1H), 6.77
7.072 (d, J ¼ 7.5 Hz, 1H), 5.094 (s, 1H, CH), 3.019 (s, 3H, CH3); (d, J ¼ 8.4 Hz, 1H), 5.12 (s, 1H, CH), 3.73 (s, 3H, OCH3); anal.
anal. calcd for C15H11N5O3: C, 58.14; H, 3.72; N, 22.59; found: C, calcd for C15H11N5O4: C, 55.28; H, 3.37; N, 21.42; found: C,
58.02; H, 3.52; N, 22.21; HR-MS m/z: calcd for C15H11N5O3 [M + 55.39; H, 3.38; N, 21.52. HR-MS m/z: calcd for C15H11N5O3 [M +
Na]+: 332.0759; found: 332.0762.
Na]+: 348.0639; found: 348.0642.
2.7.3 4c:
(trans-3,7a0)-50-amino-5-chloro-10,2,30-trioxo-
2.7.9 4i:
(trans-7,7a)-5-amino-7-(4-methoxyphenyl)-1,3-
10,20,30,7a0-tetrahydrospiro[indoline-3,70-pyrrolo[1,2-c]imid-
dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbon-
azole]-60-carbonitrile. mp ¼ 300 ꢁC; IR (KBr, cmꢀ1): 3493, 3392, itrile. mp ¼ 260 C, IR (KBr, cmꢀ1) ¼ 3390, 3340, 3258, 3210,
ꢁ
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2183, 1775, 1713, 1662, 1596, 1H NMR (400 MHz, DMSO-d6): d ¼
9.248 (s, NH), 7.308 (br s, NH2), 7.221 (d, J ¼ 8 Hz, 2H), 6.894 (d,
2.7.15 4o:
(trans-7,7a)-5-amino-7-(4-chlorophenyl)-1,3-
dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbon-
itrile. mp ¼ 281 ꢁC; IR (KBr, cmꢀ1): 3394, 3318, 3268, 3217,
3181, 2193, 1783, 1723, 1660, 1603; 1H NMR (400 MHz, DMSO-
d6): d ¼ 7.748 (br s, NH), 7.464 (d, J ¼ 8.4 Hz, 2H), 7.255 (br s,
NH2), 6.957 (d, J ¼ 8.4 Hz, 2H), 4.58 (s, 2H); anal. calcd for
1
J ¼ 8 Hz, 2H), 4.473 (s, 2H), 3.739 (s, 3H) ppm, H-NMR (300
MHz, DMSO-d6 with a drop of D2O): d ¼ 7.192 (d, J ¼ 8 Hz, 2H),
6.926 (d, J ¼ 8 Hz, 2H), 4.454 (d, J ¼ 7.5 Hz, 1H), 4.379 (d, J ¼
7.5 Hz, 1H) 3.690 (s, 3H). If DMSO was used as a solvent for 1H
NMR spectroscopy, a singlet peak was revealed for two adjacent
protons, which implied a low amount of Dn in the DMSO
solvent. But in the presence of D2O, two doublet peaks appeared
that had J ¼ 7.5 Hz. It can be inferred from these results that
just the trans diastereomer, conrmed by X-Ray crystallography,
was the pure product; anal. calcd for C14H12N4O3: C, 59.15, H,
4.25, N, 19.70; found: C, 59.23, H, 4.38, N, 19.41. HR-MS m/z:
calcd for C14H12N4O3 [M + Na]+: 307.0807; found: 307.0808.
C
13H9ClN4O2: C, 54.08; H, 3.14; N, 12.28; found: C, 54.29; H,
3.21; N, 12.22; HR-MS m/z: calcd for C13H9ClN4O2 [M + Na]+:
311.0311; found: 311.0313.
2.7.16 4p: (trans-7,7a)-5-amino-7-(2,6-dichlorophenyl)-1,3-
dioxo-2,3,7,7a-tetꢁrahydro-1H-pyrrolo-[1,2-c]imidazole-6-carbon-
itrile. mp ¼ 265 C; IR (KBr, cmꢀ1): ¼ 3432, 3340, 3227, 2182,
1791, 1712, 1659, 1602 cmꢀ1; 1H NMR (400 MHz, DMSO-d6): d ¼
11.46 (br s, NH), 7.45–7.27 (m, 3H), 7.31 (br s, NH2), 5.13 (d, J ¼
8.3 Hz, 1H), 4.85 (s, 1H); anal. calcd for C13H8Cl2N4O2: C, 48.32;
H, 2.49, N, 21.94; found: C, 48.29, H, 2.21; N, 21.81; HR-MS m/z:
calcd for C13H8Cl2N4O2 [M + Na]+: 344.9922; found: 344.9925.
2.7.10 4j:
(trans-7,7a)-5-amino-1,3-dioxo-7-(p-tolyl)-
2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]-imidazole-6-carbonitrile.
mp ¼ 275 C; IR (KBr, cmꢀ1) ¼ 3400, 3318, 3260, 2169, 1778,
ꢁ
1708, 1653, 1598; 1H NMR (400 MHz, DMSO-d6): d ¼ 8.46 (s, 1H,
NH), 7.862 (d, J ¼ 8 Hz, 2H), 7.438 (d, J ¼ 8 Hz, 2H), 7.313 (br s,
NH2), 4.448 (s, 2H, CH2); 2.389 (s, 3H); anal. calcd for
3. Experimental section
C
14H12N5O4: C, 62.69; H, 4.50; N, 20.88; found: C, 62.73; H,
All starting materials and solvents were purchased commer-
cially from Merck and Sigma-Aldrich and were used as received.
The 1H NMR spectra were determined using Bruker Avance-400
MHz spectrometers with DMSO-d6 as a solvent and tetrame-
thylsilane (TMS) as an internal standard. FT-IR measurements
were carried out using a Magna 550 apparatus by using KBr
plates. The elemental analyses (C. H. N) of the samples were
recorded using a LECO CHNS 923 analyzer. The XRD patterns
were evaluated using an X-ray diffractometer (PHILIPS, PW
1510, Netherlands) with Cu-Ka radiation (l ¼ 0.154056 nm) in
the range 2q ¼ 0–10ꢁ. The TGA-DTA analyses were performed
using a Bahr STA-503 instrument in air at a heating rate of
10 ꢁC minꢀ1. The N2 adsorption analysis was recorded at
ꢀ196 ꢁC using an automated gas adsorption analyzer (BEL
SORP mini II) and the pore diameter was calculated from the
adsorption branch of the isotherm by using the BJH model. The
FESEM analysis of the nanoparticles was carried out using
a Model FE-SEM. The TEM imaging analysis was performed
using a Philips EM208 transmission electron microscope with
an accelerating voltage of 200 kV. The EDX analysis of the
nanoparticles was carried out using a Sigma ZEISS, Oxford
Instruments Field Emission. In the NH3-TPD experiments,
samples were pre-treated at 573 K for 1 h. Aer that, NH3 was
adsorbed at 373 K for 0.5 h. Then, physically adsorbed ammonia
was removed with a pure nitrogen ow at 373 K. XPS spectra
were recorded using a ESCA System 100 spectrometer (VSW
Scientic Instruments, Manchester).
4.22; N, 20.52; HR-MS m/z: calcd for C14H12N5O4 [M + Na]+:
291.0858; found: 291.0859.
2.7.11 4k: (trans-7,7a)-5-amino-1,3-dioxo-7-phenyl-2,3,7,7a-
tetrahydro-1H-pyrrolo[1,2-c]-imidazole-6-carbonitrile. mp
¼
275 ꢁC; IR (KBr, cmꢀ1): 3400, 3318, 3260, 2169, 1778, 1708, 1653,
1598; 1H NMR (400 MHz, DMSO-d6): d ¼ 8.504 (br s, NH), 7.313
(br s, NH2), 7.110–7.115 (m, 5H, Ar–H), 4.428 (s, 2H, CH2); anal.
calcd for C13H10N4O2: C, 61.41, H, 3.96; N, 22.03; found: C,
61.29; H, 3.88; N, 22.22. HR-MS m/z: calcd for C13H10N4O2 [M +
Na]+: 277.0701; found: 277.0705.
2.7.12 4l:
(trans-7,7a)-5-amino-7-(3,5-dimethoxyphenyl)-
1,3-dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-car-
bonitrile. mp ¼ 245 ꢁC; IR (KBr, cmꢀ1): 3402, 3339, 3241, 3010,
2967, 2838, 2771, 2195, 1744, 1661; 1H NMR (400 MHz, DMSO-
d6): d ¼ 9.815 (br s, NH), 8.323 (br s, NH2), 7.608 (s, 1H), 7.591 (d,
J ¼ 8.0 Hz, 1H), 7.201 (d, J ¼ 8.0 Hz, 1H), 4.636 (d, J ¼ 8 Hz, 2H),
3.889 (d, J ¼ 8 Hz, 6H); anal. calcd for C15H14N4O4: C, 57.32; H,
4.48; N, 17.82; found: C, 57.29; H, 4.58; N, 17.79. HR-MS m/z:
calcd for C15H14N4O4 [M + Na]+: 337.0912; found: 337.0915.
2.7.13 4m:
(trans-7,7a)-5-amino-7-(4-bromophenyl)-1,3-
dioxo-2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]imidazole-6-carbon-
itrile. mp ¼ 271 ꢁC; IR (KBr, cmꢀ1): 3391, 3313, 3259, 3209,
2182, 1782, 1718, 1645, 1623; 1H NMR (400 MHz, DMSO-d6): d ¼
11.49 (s, 1H), 7.59 (d, J ¼ 8.4 Hz, 2H), 7.39 (br s, 2H), 7.30 (d, J ¼
8.4 Hz, 2H) 4.57 (d, J ¼ 9.2 Hz, 1H) 4.54 (d, J ¼ 9.2 Hz, 1H) ppm;
anal. calcd for C13H9BrN4O2: C, 46.85, H, 2.72; N, 16.82; found:
C, 46.92; H, 2.69; N, 16.72; HR-MS m/z: calcd for C13H9BrN4O2
[M + Na]+: 354.9806; found: 354.9809.
3.1. Preparation and characterization of the catalyst
2.7.14 4n: (trans-7,7a)-5-amino-7-(3-nitrophenyl)-1,3-dioxo-
2,3,7,7a-tetrahydro-1H-pyrrolo[1,2-c]-imidazole-6-carbonitrile.
mp ¼ 265 ꢁC; IR (KBr, cmꢀ1): 3444, 3347, 3218, 2180, 1789, 1751,
1655; 1H NMR (400 MHz, DMSO-d6): d ¼ 11.55 (s, 1H), 8.21–7.70
(m, 4H), 7.51 (br s, 2H), 4.79 (d, J ¼ 8.8 Hz, 1H), 4.66 (d, J ¼
All of the steps for the functionalization of the modied surface
of the mesoporous SBA-15 have been shown in Scheme 4.
3.2. Preparation of the NNBIA ligand
8.8 Hz, 1H); anal. calcd for C13H9N5O4: C, 52.16, H, 3.03; N, 1 mmol of 1,2-diaminoethane was added to a mixture of 2 mmol
23.41; found: C, 51.92; H, 2.96; N, 23.72; HR-MS m/z: calcd for powdered isatoic anhydride in 5 mL of hot water. The reaction
C
13H9N5O4 [M + Na]+: 322.0552; found: 322.0554.
was stirred and reuxed for 3 h. Then, the reaction mixture was
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Scheme 4 The different steps for synthesis of W(IV)/NNBIA–SBA-15.
le to stand overnight to generate crystals of the product. The
crystals were ltered and washed with EtOH and then dried to
obtain the pure product. The structure of the ligand, NNBIA,
was conrmed by the 1H NMR that is presented in Fig. 10.
3.3. Preparation of SBA-15
4.0 g of pluronic 123 triblock copolymers (EO20–PO70–EO20), as
templates, were dissolved in 2.0 (M) aq. HCl (120 mL) and
distilled water (15 mL) in a 250 mL round-bottom ask. The
mixture was stirred at room temperature for 4 h. Then 8.5 g of
tetraethylorthosilicate was added dropwise to the solution. The
temperature of the reaction mixture was kept at 35 ꢁC and it was
stirred for 8 h. The synthesized gel was heated under static
conditions in a Teon-lined autoclave for 24 h at 100 ꢁC. A white
solid precipitated and was ltered and washed with deionized
water. The residual organic materials were removed by calci-
nation at 550 C for 8 h.42,48
ꢁ
3.4. Organofunctionalization of SBA-15
In a dry Schlenk ask, 1 g of SBA-15, that was activated under
vacuum at 150 ꢁC for 3 h, was suspended in dry toluene. Then,
3 mmol of (3-chloropropyl)triethoxysilane was added to the
above suspension solution. The reaction mixture was reuxed
under nitrogen for 6 h. Finally, purication of the Cl-
Fig. 10 1H NMR spectrum of the ligand, NNBIA, in DMSO-d6.
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functionalized SBA-15 was achieved by Soxhlet extraction with important role in developing the synthesis of 2-azapyrrolizidine
dichloromethane for 8 h.
alkaloids.
3.5. Immobilization of the NNBIA ligand over SBA-15–Cl
Conflicts of interest
The SBA-15 with chloropropyl linkers (1 g) was suspended in
absolute ethanol (60 mL) by sonication in a 250 mL round-
bottom ask to form a uniform dispersion. Then, 0.298 g (1
mmol) of the NNBIA ligand was added to the solution and the
reaction mixture was reuxed for 18 h. The precipitates were
washed repeatedly with toluene to remove the unreacted
substrate. Then, they were put in a hot-air oven at 90 ꢁC and
were le to stand overnight to dry and furnish the functional-
ized SBA-15.
There are no conicts to declare.
Acknowledgements
The authors are grateful to the University of Kashan for sup-
porting this work (grant no. 159148/73).
Notes and references
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