ZIF-8 nanoparticles as an efficient and reusable catalyst for the Knoevenagel synthesis of cyanoacrylates and 3-cyanocoumarins

Article abstract of DOI:10.1016/j.tetlet.2016.11.070

Zeolitic imidazolate framework (ZIF-8) particles with an average size of ca. 355 nm and a specific surface area of 1786 m².g^?1were used as an heterogenous catalyst for the Knoevenagel synthesis of α,β-unsaturated cyanoesters and 3-cy

Full text of DOI:10.1016/j.tetlet.2016.11.070

Accepted Manuscript
ZIF-8 nanoparticles as an efficient and reusable catalyst for the Knoevenagel
synthesis of cyanoacrylates and 3-cyanocoumarins
Oleksii Kolmykov, Nassima Chebbat, Jean-Marc Commenge, Ghouti Medjahdi,
Raphaël Schneider
PII:
S0040-4039(16)31551-9
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.11.070
TETL 48356
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
30 August 2016
14 November 2016
16 November 2016
Please cite this article as: Kolmykov, O., Chebbat, N., Commenge, J-M., Medjahdi, G., Schneider, R., ZIF-8
nanoparticles as an efficient and reusable catalyst for the Knoevenagel synthesis of cyanoacrylates and 3-
cyanocoumarins, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.11.070
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ZIF-8 nanoparticles as an efficient and reusable catalyst for the
Knoevenagel synthesis of cyanoacrylates and 3-cyanocoumarins
a
a
a
Oleksii Kolmykov , Nassima Chebbat , Jean-Marc Commenge , Ghouti
b
a,*
Medjahdi , Raphaël Schneider
a
Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), UMR 7274,
CNRS, 1 rue Grandville, BP 20451, 54001 Nancy Cedex, France
b
Institut Jean Lamour (IJL), Université de Lorraine, CNRS, UMR 7198, CNRS, BP 70239,
5
4506 Vandoeuvre-lès-Nancy Cedex, France
*
Corresponding author. Tel. :+33 3 83 17 50 53.
E-mail address : raphael.schneider@univ-lorraine.fr
Abstract
Zeolitic imidazolate framework (ZIF-8) particles with an average size of ca. 355 nm and a
2
-1
specific surface area of 1786 m .g were used as an heterogenous catalyst for the
Knoevenagel synthesis of α,β-unsaturated cyanoesters and 3-cyanocoumarins. The
preparation of 3-cyanocoumarins was efficiently achieved using DMF as solvent and
conducting the condensation at 80°C. When the reaction was performed in ethanol, only the
intermediates α,β-unsaturated cyanoesters were obtained. The ZIF-8 catalyst can be reused up
to five times without any degradation in activity. SEM and XRD analyses demonstrate the
high stability of ZIF-8 crystals during the recycling test.
Keywords: ZIF-8; Knoevenagel; α,β-unsaturated cyanoesters; 3-Cyanocoumarins
Introduction
The Knoevenagel condensation is one of the most efficient and thus widely used method for
1
,2
the creation of carbon-carbon double bonds. The α,β-unsaturated compounds obtained after
3
the condensation are highly valuable intermediates in the synthesis of natural products,
4
5
drugs, functional polymers, etc. The Knoevenagel condensation is generally accomplished
1

by treating a carbonyl compound with an active methylene compound and using
6
,7
homogeneous catalysts like amines (ammonia, piperidine, pyridine, etc). These catalysts,
which can only hardly be recovered after reaction, are associated with environmental
pollution because large quantities of waste are produced and their use in industrial processes
is therefore limited.
Over the past decade, various heterogeneous catalysts have been developed for the
Knoevenagel reaction including ion-exchange resins, Montmorillonite KSF, modified silica,
8
-14
Al oxides, mixed oxides of Mg and Al, choline chloride, etc but some of them suffer from
limitations like harsh reaction conditions, long reaction times and moderate yields. Metal
organic frameworks (MOFs) are an emerging class of heterogeneous catalysts combining the
advantages of heterogeneous catalysts (ease of separation after reaction, reusability, stability)
with those of homogeneous catalysts (high activity under mild reaction conditions, selectivity)
because both their porosity and the structure of active sites can easily be tuned by simply
1
5,16
changing either the synthetic conditions, the organic linkers or the metal cations.
Among
MOFs, the zeolitic imidazolate framework 8 (ZIF-8) is a highly promising material
2
-1
associating the properties of MOFs (theoretical BET surface area of 1947 m .g , pore
diameter of 11.6 Å and aperture between two cages of 3.4 Å) with the thermal (up to 600°C
1
7-19
under N
2
) and the chemical stabilities of zeolites.
ZIF-8 is constructed from tetrahedral
2
+
-
units in which each Zn atom connects four imidazolate (mim ) ligands to form neutral
frameworks and thus ZIF-8 exhibits both Lewis acid and Brönsted base properties. ZIF-8
2
0
21
particles have found many applications in gas storage, gas separation but their potential as
heterogeneous catalysis in fine chemicals industry (Knoevenagel condensations, trans-
1
9,22-25
esterification, and Friedel-Crafts alkylation) has only emerged in recent years.
Herein, we report the successful use of ZIF-8 particles for the efficient synthesis of α,β-
unsaturated cyanoesters and of 3-cyanocoumarins (3-cyano-2H-1-benzopyran-2-ones) using
2
-hydroxy aromatic aldehydes and ethyl cyanoacetate as starting materials. The ZIF-8 catalyst
could be reused up to five times without decrease of catalytic activity. The obtained
coumarins have been demonstrated to be highly valuable products or intermediates in
2
6,27
28,29
pharmaceutical synthesis,
as additives in food and cosmetics
and as fluorescent
3
0,31
dyes.
Results and discussion
2

ZIF-8 particles were prepared via an environmentally sustainable method by reacting
Zn(NO with 2-methylimazole (Hmim) in water for 1 h (see ESI). The scanning electron
)
3 2
microscopy (SEM) image shows that the crystals obtained after centrifugation, washing and
drying have an average diameter of 355 ± 71 nm and exhibit the stable rhombic dodecahedron
morphology of ZIF-8 (Fig. 1a-b). In the X-ray diffraction (XRD) pattern (Fig. 1c), the relative
intensities and prominent (011), (002), (112), (022), (013), and (222) peaks positions are in
good agreement with previous reports and confirm the sodalite structure, which is the typical
1
7-19
structure of ZIF-8.
The well-defined peaks demonstrate the high crystallinity of ZIF-8
particles prepared. The liquid nitrogen adsorption/desorption isotherms at 77 K show that
3
2
2
-1
ZIF-8 crystals exhibit type I isotherms and that their specific surface is 1786 ± 32 m .g ,
indicating their microporous nature (Fig. 1d). The micropore volume was estimated to be of
3
-1
ca. 0.648 cm .g and the pore size of 12.8 Å.
Fig. 1. (a) SEM image, (b) the corresponding size distribution, (c) XRD pattern and (d)
nitrogen sorption isotherms measured at 77 K of the ZIF-8 crystals used in this study (black
and red data correspond to the adsorption and desorption branches, respectively).
3

The reaction of 2-hydroxybenzaldehyde with ethyl cyanoacetate was first investigated to
optimize the reaction conditions. According to our previous results related to ZIF-8-catalyzed
Knoevenagel condensations [19, 24, 25], initial experiments were conducted in ethanol or
toluene at room temperature and using 6 mol. equiv. of active methylene compound relative
to the aldehyde. Using 8 mol% of ZIF-8 relative to 2-hydroxybenzaldehyde and EtOH as
solvent, the reaction proceeded to completion after 13 h but surprisingly, only the α,β-
unsaturated cyanoester 1a was obtained in 90% (Table 1, entry a). Neither the cyclisation of
1
1
a into coumarin nor the Michael addition of the active methylene compound on the C=C of
a were observed. An increase of the catalyst loading (16 mol%) improved slightly the
reaction time (11 h) but has no effect on the structure of the final product. The increase of the
reaction temperature didn’t afford better results and only the reaction time was decreased (10
and 7 h for reaction temperatures of 50 and 80°C, respectively). When performing the
reaction at room temperature in ethanol, a variety of 2-hydroxy aromatic aldehydes were
investigated. The presence of electron-withdrawing groups (Table 1, entries b, c and f) or of
electron-donating groups (Table 1, entries d and e) relative to the aldehyde only slightly
affects the reaction yields. An ortho substitution of the aldehyde is also well tolerated (Table
1
, entry e). The low reactivity of 5-nitro-2-hydroxybenzaldehyde may originate from the
difficulty of this substrate to interact with the active sites of the ZIF-8 particles (Table 1, entry
1
b). H NMR analyses demonstrate that only the (E) isomer of compounds 1 is obtained via the
3
3
ZIF-8 catalyzed Knovenagel reaction. Finally, we suppose that the strong association of the
2
+
phenolate function with the surface Zn atoms of ZIF-8 crystals hinders its nucleophilic
attack on the ester function and thus the synthesis of 3-cyanocoumarins.
4

Table 1. ZIF-8 catalyzed Knoevenagel condensation of 2-hydroxyaldehydes with ethyl
cyanoacetate in ethanol at room temperature.
Starting
ZIF-8
Time
(h)
Yield
a
b
Entry hydroxyaldehyde
(mol%)
Product 1
(%)
a
8
13
11
90
93
1
6
b
c
d
16
16
16
15
15
15
23
90
89
e
f
16
16
18
19
95
95
g
16
20
93
a
Only the (E) isomer of compounds 1 was obtained after reaction.
b
Yields refer to the isolated products after silica gel column chromatography.
2
+
Thus, we decided to use a more polar solvent to dissociate the phenolate from Zn cations
and to favor the nucleophilic attack on the ester function. When the condensation was
5

conducted at 80°C in DMF, the 3-cyanocoumarins 2 were generally obtained with excellent
3
4
yields (Table 2). In the absence of the ZIF-8 catalyst, the starting materials were recovered
unchanged even after extended heating (48 h) in DMF. The key role played by the solvent in
the cyclisation of compounds 1 into coumarins 2 was further proved by reacting compound 1a
with the ZIF-8 catalyst in DMF. After 10 h heating at 80°C, product 2a was obtained in 98%
yield. As previously observed for the preparation of compounds 1, bromo, tertiary amine or
methoxy substituents on the aromatic ring do not affect the efficiency of the reaction. The
sterically hindered 3- or 5-methoxy 2-hydroxybenzaldehydes (Table 2, entries e and f)
required a longer reaction time compared to 4- or 5-subtituted aldehydes to yield coumarins 2
but the reaction yield was not affected (88 and 93%, respectively). Surprisingly, no product
was detected using 5-nitro-2-hydroxybenzaldehyde as starting material (entry b). In a control
experiment, we reacted 2-hydroxybenzaldehyde with ethyl cyanoacetate in the presence of 1
equiv. of nitrobenzene. Product 2a was not detected, indicating that the electrostatic
interactions between the nitro group and the active sites of the ZIF-8 catalyst may be at the
origin of the problem observed as previously observed for the preparation of compound 1b.
Noteworthy is also that in all these condensations, the nucleophilic attack of the phenolate
occurred only on the ester function leading to 3-cyano substituted coumarins and that the
formation of ethyl 2-imino-2H-chromene-3-carboxylate was not detected.
6

Table 2. ZIF-8 catalyzed Knoevenagel condensation of 2-hydroxyaldehydes with ethyl
cyanoacetate in DMF at 80°C.
Entry
Starting 2-
ZIF-8
(mol%)
8
Time
(h)
9
Product 2
Yield
a
hydroxyaldehyde
(%)
86
91
a
b
c
d
16
8
16
16
16
24
24
24
0
90
89
e
f
16
16
16
36
48
18
93
88
95
g
a
Yields refer to the isolated products after silica gel column chromatography.
Finally, the recyclability and the stability of the ZIF-8 catalyst were investigated for the
synthesis of 3-cyanocoumarins. After the first run, ZIF-8 particles were recovered by
centrifugation and reused after a simple washing with dichloromethane. Using the
condensation of 2-hydroxybenzaldehyde with ethyl cyanoacetate as representative, the
catalyst could be reused at least five times with negligible decrease of activity (89% of
th
isolated yield after the 5 run) (Fig. 2.). Powder XRD analysis and SEM further demonstrate
that neither the crystallinity nor the morphology of ZIF-8 particles were altered during
7

recycling experiments, thus demonstrating their high stability (Fig. S1 in the supplementary
data).
1
00
8
6
4
2
0
0
0
0
0
0
1
2
3
4
5
6
Cycle number
Fig. 2. Plot of ZIF-8 catalyzed Knoevenagel reaction yield versus cycle number.
Conclusion
ZIF-8 particles with an average diameter of ca. 355 nm were easily prepared in water from
Zn(NO
3
2
) and 2-methylimidazole. These particles were demonstrated to be an efficient
heterogeneous catalyst for the Knoevenagel synthesis of α,β-unsaturated cyanoesters and of 3-
cyanocoumarins using 2-hydroxy aromatic aldehydes and ethyl cyanoacetate as starting
materials. For the synthesis of 3-cyanocoumarins, the catalyst operates under relatively mild
conditions (80°C in DMF) affording products in good to excellent yields ranging from 89 to
9
5%. Moreover, the ZIF-8 catalyst can be easily separated by centrifugation from reaction
products after completion of the reaction and recycled at least five times with negligible
changes in catalytic performances. Further studies on extending the scope of ZIF-8 particles
as catalyst in organic reactions are currently in progress in our laboratory.
Acknowledgements
We thank Kevin Mozet (LRGP, Université de Lorraine) for BET measurements and Olivier
Fabre (LCPM, Université de Lorraine) for NMR experiments.
Supplementary data
8

Supplementary data associated with this article can be found, in the online version, at
http://dx.doi.org/
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2. A typical experimental procedure for the ZIF-8 catalyzed synthesis of 3-cyanocoumarins.
3
3
In a Pyrex screw-cap tube, the 2-hydroxy aromatic aldehyde (0.5 mmol) was dissolved in 5
mL of DMF. The ZIF-8 catalyst (18 mg, 16 mol%) was added and the mixture stirred for 5
min. Ethyl cyanoacetate (3 mmol) was then injected. The reaction mixture was heated at 80°C
for the time indicated in Table 2 and the progress of the reaction was monitored by TLC.
After complete conversion, as indicated by TLC, the reaction mixture was cooled to room
temperature and the ZIF-8 was separated by centrifugation. The organic was concentrated
under reduced pressure and the crude reaction mixture was directly charged onto a small silica
gel column and eluted with a mixture of ethyl acetate/petroleum ether to afford the pure 3-
cyanocoumarin 2.
10

Graphical abstract
11

Highlights
→
→
→
→
ZIF-8 mediated synthesis of cyanoacrylates and 3-cyanocoumarins is reported.
The solvent plays a key role on the outcome of the reaction.
3-Cyanocoumarins are obtained under mild conditions (DMF at 80°C).
The catalyst is stable and reusable up to five cycles without any loss in activity.
12