Green synthesis of formamides using the Natrolite zeolite as a natural, efficient and recyclable catalyst

Article abstract of DOI:10.1016/j.molcata.2013.04.001

Chemoselective N-formylation of different amines was carried out with formic acid in the presence of the Natrolite zeolite as an efficient, stable and natural heterogeneous catalyst to give the corresponding formamides at room temperature under solvent-free conditions. This method has the advantages of high yields, mild conditions, simple methodology, easy work up and short reaction times. The catalyst was characterized by different techniques such as powder XRD, XRF, TGA-DTA, SEM and FT-IR spectroscopy. The Natrolite zeolite was recovered and reused several times without the significant loss of its catalytic performance.

Full text of DOI:10.1016/j.molcata.2013.04.001

Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Green synthesis of formamides using the Natrolite zeolite as a natural, efficient
and recyclable catalyst
∗
Davood Habibi , Mahmoud Nasrollahzadeh, Hesam Sahebekhtiari
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Chemoselective N-formylation of different amines was carried out with formic acid in the presence of
the Natrolite zeolite as an efficient, stable and natural heterogeneous catalyst to give the corresponding
formamides at room temperature under solvent-free conditions. This method has the advantages of high
yields, mild conditions, simple methodology, easy work up and short reaction times. The catalyst was
characterized by different techniques such as powder XRD, XRF, TGA–DTA, SEM and FT-IR spectroscopy.
The Natrolite zeolite was recovered and reused several times without the significant loss of its catalytic
performance.
Received 15 January 2013
Received in revised form 31 March 2013
Accepted 2 April 2013
Available online xxx
Keywords:
N-Formylation
Formic acid
©
2013 Elsevier B.V. All rights reserved.
Amine
Chemoselectivity
Natrolite zeolite
Heterogeneous catalyst
1
. Introduction
catalysts and formation of side products. Recently polyethylene
glycol has been reported as a medium for formylation of ani-
line derivatives with formic acid [18]. However, the success of
this method is limited only to aromatic primary amines, and the
method does not avoid the use of organic solvent. Thus, there is
a drastic need to develop a simple and practical method for the
N-formylation of amines under mild conditions.
Formamides are valuable intermediates in the construction
of various pharmaceutical compounds [1,2] and are also useful
reagents in Vilsmeier–Haack formylation reactions [3]. Moreover,
they are Lewis bases and can catalyze several organic transforma-
tions [4,5].
Protection of functional groups plays an important role in the
synthesis of complex organic molecules such as natural products.
The formyl group is also an important aminoprotecting group in
peptide synthesis [6]. A number of formylation methods have been
reported in recent years. Acetic formic anhydride [7] has widely
been used as a formylating reagent, but it is sensitive to moisture
and cannot be stored for a long period since it decomposes to acetic
acid and carbon monoxide. Many other useful formylation reagents
have been reported such as chloral [8], activated formic acid using
DCC [9] or EDCI [10], activated formic esters [11–14], ammonium
formate [15], 2,2,2-trifluoroethyl formate [16] and aq. 85% formic
acid and ZnO [17]. However, many of these methods suffer from
different disadvantages such as long reaction times, high temper-
ature, application of expensive and toxic formylating reagents and
There has been a tremendous interest in various chemical
transformations performed by application of inexpensive and non-
corrosive heterogeneous catalysts such as zeolites [19]. These
reactions occur with better efficiency, higher purity of the products,
easier work up and ecological advantages especially for industrial
processes. Application of zeolites has received considerable atten-
tion in recent decades due to their unique physical and chemical
properties such as shape selectivity, acidic and basic nature and
their thermal stability [20,21]. The Natrolite zeolite is one of zeolites
with Al Si O main structural unit and the framework constructed
2
3
10
from chains of corner-sharing Al and Si oxygen tetrahedral which
ordered Na+ ions and H O molecules fill the voids of the frame-
2
work [22–24]. The structure has a typical zeolite openness about it
that allows molecules and large ions to reside and actually move
around inside the overall framework. Also, it contains eight chan-
nels that allow water and large ions to travel into and out of the
crystal structure. Size of these channels controls the size of the
molecules or ions, and therefore the Natrolite zeolites can act as a
chemical sieve [23]. Our recent study has shown that the Natrolite
zeolite can be used as a very active catalyst in the organic synthesis
[24,25].
Abbreviations: XRD, X-ray powder diffraction; XRF, X-ray fluorescence; TGA,
thermogravimetric analysis; DTA, differential thermal analysis; SEM, scanning elec-
tron microscopy; FT-IR spectroscopy, Fourier transform infrared spectroscopy.
∗ Corresponding author. Tel.: +98 811 8282807; fax: +98 811 8380709.
E-mail address: davood.habibi@gmail.com (D. Habibi).
1
381-1169/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2013.04.001

D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
149
2
.2. General procedure for the N-formylation of amines using the
RR'NH
HCOOH
Solvent-free,r.t.
Natrolitezeolite
RR'NCHO
Natrolite zeolite
To a mixture of HCO H (99% purity, 0.05 mL, 1.2 mmol) and
2
Scheme 1. General N-formylation method.
the Natrolite zeolite (0.02 g), was added an amine (1.0 mmol) and
the reaction mixture rapidly was stirred at room temperature. The
progress of the reaction was monitored by TLC. After completion
of the reaction, EtOAc was added and the Natrolite zeolite was
removed by filtration. After removal of the solvent, the pure prod-
uct was obtained. The physical data of the known compounds were
identical with those reported in the literature [8,15–18,48–56].
4-Phenylpiperazine-1-carbaldehyde (Table 2, entry 15):
Due to the safety considerations, we must avoid methods which
use additional reagents or expensive catalysts. Also, the use of haz-
ardous organic solvents leads to complex isolations and recovery
procedures. However, solvent-free systems remain a significant
option for achieving more environmentally friendly synthetic pro-
tocols.
In the course of our researches on the applications of heteroge-
neous reagents for development of the synthetic methodologies
and synthesis of the nitrogen-containing compounds [24–40],
herein we report a new protocol for the activation of formic acid
as an N-formylating agent using the Natrolite zeolite [41] at room
temperature under solvent-free conditions (Scheme 1). Apparently,
no methodology has been reported where formic acid is used as the
sole formylating agent in the presence of the natural catalyst and
in solvent-free conditions, so far.
A number of formylating agents such as DMF, ethyl formate,
ammonium formate, sodium formate, formyl halides or anhydrides
and esters, cyanomethyl formate, isopropenyl formate, chloral and
,2,2-trifluoroethyl formate have been reported in recent years
7,8,15,16,42–45]. However, these formylating agents suffer from
the different disadvantages such as lack of generality, thermal
instability, sensitivity to moisture, toxicity, high cost, easy degra-
dation upon storage, difficulties in preparation or availability of
reagents, long reaction times, harsh reaction conditions, forma-
tion of side products, no chemoselectivity and difficulties in the
work-up stages. Among the formylating agents, formic acid is nei-
ther explosive nor flammable. In addition, it is cheap, not volatile
and stable in the presence of moisture and efficient reagent which
can be easily stored. For these reasons, formic acid has received
much attention among formylating agents in the N-formylation of
amines.
◦
−1
M.p. 82–84 C; FT-IR (KBr, cm ): 2916, 2814, 1654, 1632, 1599,
1499, 1447, 1405, 1385, 1366, 1350, 1334, 1283, 1254, 1239, 1197,
1149, 1092, 1057, 1033, 1007, 916, 766, 693; 1H NMR (300 MHz,
CDCl3): ıH 10.35 (s, 1H, cis), 8.55 (s, 1H, trans), 6.92–7.33 (m, 5H,
Ar H), 3.72–3.16 (m, 8H); 13C NMR (125 MHz, CDCl3): ıC 161.2,
151.4, 129.7, 121.4, 117.6, 50.9, 49.8, 46.0, 40.4.
3. Results and discussion
The influence of various parameters such as non-framework
cations, Si/Al ratio of zeolite, nature of active sites, catalyst con-
centration and molar ratio of the reactants and recycling of the
catalysts were considered upon the conversion of reactants and
the formation of desired products in the N-formylation of amines.
No reaction was observed when a mixture of aniline (1.0 mmol)
and formic acid (99% purity, 0.05 mL, 1.2 mmol) was stirred for
5 h at room temperature. However, the N-formylation of amines
was rapidly increased upon addition of the Natrolite zeolite to the
reaction mixture.
2
[
3.1. Physico-chemical characterization of the Natrolite zeolite
The Natrolite zeolite can be classified as fibrous zeolites with
small pores (channels in the framework structure) which mostly
consists of 8 members of oxygen ring systems (the diameter of their
pores < 4.5 A˚ ). Its catalytic properties are very much depending on
both their chemical and physical aspects and was characterized
using the powder XRD, XRF, TG-DTA, SEM and FT-IR spectroscopy
[23–25,41,57].
2
. Experimental
2.1. Instruments and reagents
3.2. Optimization of the reaction conditions
All reagents were purchased from the Merck and Aldrich chem-
Initial studies were performed in order to optimize the reac-
tion conditions for the N-formylation of amines with formic acid in
the presence of the Natrolite zeolite. The best result was obtained
with the amine/formic acid molar ratio of 1–1.2 with 0.02 g of the
Natrolite zeolite at room temperature under solvent-free condi-
tions (Table 1, entry 2).
ical companies and used without further purification. Products
were characterized by different spectroscopic methods (IR, FT-
1
13
IR, H NMR and C NMR spectra), elemental analysis (CHN) and
1
3
melting points. The C NMR spectra were recorded in acetone,
DMSO and CDCl3. H NMR spectra were recorded on a Bruker
1
Avance DRX 90, 200, 300, 400 and 500 MHz instruments. The chem-
ical shifts (ı) are reported in ppm relative to the TMS as internal
standard. J values are given in Hz. IR (KBr) spectra were recorded on
a Shimadzu 470 and Perkin-Elmer 781 spectrophotometer. Melt-
ing points were taken in open capillary tubes with a BUCHI 510
melting point apparatus and were uncorrected. Elemental analy-
sis was performed using Heraeus CHN-O-Rapid analyzer. TLC was
performed on silica gel polygram SIL G/UV 254 plates. A Metrohm
A series of aromatic, heterocyclic and aliphatic amines were
converted into the corresponding N-formyl amines with formic
acid by the Natrolite zeolite in high yields under solvent-free con-
ditions at room temperature (Table 2). Anilines containing both
Table 1
Reaction of 2-chloroaniline and formic acid promoted by Natrolite zeolite at room
temperature under solvent-free conditions.
6
32 pH-meter with a Metrohm double junction glass electrode
Entry Natrolite
zeolite (g)
Amine
(mmol)
HCOOH
(mmol)
Time
(min)
Yield (%)
was used for pH monitoring. The Natrolite and Heulandite zeolites
were provided from the Hormak area (city of Zahedan, Sistan &
Baluchestan province, Iran) and Semnan city (Semnan province,
Iran), respectively [23–25,41,46]. The ␤-zeolite (Si/Al ratio = 10)
was synthesized according to the reported procedure [47] and
the Na-Y zeolite (Si/Al ratio = 2.35) provided from the Strem
Chemicals.
a
1
2
3
4
5
0.02
0.02
0.02
0.04
0.04
1.0
1.0
1.0
1.0
1.0
1.0
1.2
1.5
1.2
1.5
22
20
20
20
20
90
95
95
94
96
a
Monitored by GC and TLC.

1
50
D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
Table 2
Green N-formylation of different amines by the Natrolite zeolite.
a
Entry
1
Substrate
NH
Product
Time (min)
20
Yieldb (%)
89
Ref.c
[17]
2
NHCHO
NHCHO
Cl
Cl
2
3
4
20
25
50
95 (94, 94, 93, 92)d
[17]
[17]
[17]
NH2
O
2
N
NH
2
O2N
NHCHO
83
92
NH2
NHCHO
HO
Cl
HO
Cl
NH2
NHCHO
NHCHO
5
6
10
15
90
91
[18]
[17]
Br
NH2
Br
Me
Me
7
20
20
91
91
[17]
NH2
Me
NHCHO
Me
NH
2
Me
NHCHO
8
9
Aldrich
Me
MeOC
Me
NH
2
MeOC
Me
NHCHO
20
15
90
92
[17]
[18]
NH2
NHCHO
1
1
0
1
NH
2
NHCHO
20
40
90
[58]
N
H
N
CHO
1
1
2
3
86
89
[49]
[17]
H
N
CHO
N
120
1
4
NHMe
N(CHO)Me
40
75
[46]
HN
NPh
OHCN
NPh
15
16
17
30
30
25
80
88
92
This work
[18]
CH NH
CH NHCHO
2
2
2
O
NH
O
NCHO
[17]
NC
OH
1
8
9
No reaction
No reaction
50
40
–
–
–
–
CH OH
1
2
a
b
c
Reaction conditions: formic acid (99% purity, 0.05 mL, 1.2 mM), the Natrolite zeolite (0.02 g), amine (1.0 mM), under solvent-free conditions at room temperature.
Yield refers to the pure isolated product.
The compound reported in the literature.
d
The yields of four subsequent runs by using the same recovered catalyst.

D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
151
Scheme 2. Chemoselective N-formylation of amines.
electron-releasing and electron-withdrawing groups underwent
the conversion in good yields (Table 2, entries 2–11). Interestingly,
the N-formylation of 4-nitroaniline was carried out in 83% isolated
yield (Table 2, entry 3), while Choi and co-workers were not able
to do it, probably due to the low basicity of the amino group which
is not easily acylated [48].
technique, the important composition of the Natrolite zeolite is
Al O , SiO , Na O and H O.
2
3
2
2
2
The strength and number of the acid sites of a zeolite are impor-
tant in the study of zeolite reactivity and selectivity. The activity of
the Natrolite zeolite in acid catalyzed N-formylation of amines ori-
ginates from the tetrahedral framework aluminium atoms which
induce a potentially active acid site. Silicates do not have acidic
character and there is one type of acid catalytic activity associated
with the Natrolite zeolite namely Lewis acidity which corresponds
to an electron pair acceptor. Since the Al3+ ions of the Lewis acid
sites have tendency to acquire a pair of electrons to fill its vacant p
orbitals, therefore, the amount of acidity depends on the aluminium
content of the zeolite. When cations (Na, K or Cs) in the Natrolite
zeolite are replaced by proton (via ammonium ion exchange and
3.3. Selectivity of the method
O-Formylation of alcohol or phenol derivatives was not suc-
cessful under the applied reaction conditions, so no O-formylation
was observed with 4-hydroxybenzonitrile (Table 2, entry 18) and
benzyl alcohol (Table 2, entry 19). Thus a substrate bearing both
the NH2 and OH groups will only be N-formylated indicating
the high chemoselectivity of the applied method (Table 2, entry 4,
Supporting Information, Fig. 8).
Primary amines are easily N-formylated and the procedure is
applicable for secondary amines as well but they need longer reac-
tion times (Table 2, entries 12–15). The difference in the reactivity
of amines shows chemoselectivity of this method, thus when a mix-
ture of primary and secondary amine was exposed to formic acid
+
thermal decomposition of the ammonium form to form the H ),
Brønsted acid site is obtained. The strength of these acid sites is
found to vary with (i) zeolite structure framework, (ii) Si/AI ratio,
and (iii) metal ions exchanges in the zeolite structure framework
[
59].
3.5. Proposed mechanism
(
1 equiv.), only primary amine was formylated (Scheme 2).
It seems likely that almost all reagents utilized in the present
study can reach the active sites of the catalyst surface. The Natro-
lite zeolite probably has an important role in promotion of the
N-formylation reaction as a Lewis acid and the plausible mecha-
nism is shown in Scheme 3.
3
.4. Nature of active sites
Zeolites are comprised of channels and cavities of molecular
dimensions ranging from 3 to 10 A˚ in diameter. The framework
structure of zeolite consists of a three dimensional network of SiO4
The XRF results show that the acidic sites on the surface of the
Natrolite zeolite are Al O which can catalyze this reaction [23]. The
2
3
Natrolite zeolite may bind with the carbonyl group of formic acid
and thus will enhance its electrophilic character to facilitate the
subsequent nucleophilic attack of the amine lone pair electrons.
A similar mechanism has been reported for the N-formylation of
amines using the ZnCl2 catalyst [52].
and AlO4 tetrahedra linked together by oxygen (Fig. 1) which the
+
ordered Na ions and H O molecules fill the voids of the framework
2
[
22–24].
The negative charge of the aluminosilicate structure of a zeo-
lite is directly related to the permanent negative charge generated
by Al3+ substitution for Si4+ in the tetrahedral lattice. The nega-
tive charge on alumina tetrahedra is neutralized by monovalent or
divalent cations such as sodium and calcium which are located in
the structural channel cavities and resulting in an electrically neu-
3.6. Effect of the amount of formic acid
Reported methods for the N-formylation of amines usually suf-
fer from the use of the excess of formic acid which cannot be easily
recovered causing the waste generation or pollution (Table 3).
While in our proposed method there is relatively no formic acid
residue after completion of the reaction which is very important
from both the economical and environmental points of view.
Table 3 is clearly informative and shows the application of dif-
ferent reagents in the N-formylation of amines. Nevertheless some
disadvantages of the literature works are as below:
tral framework. H O molecules are also located in the structural
channels and are present in different concentrations. In the Natro-
lite zeolite, each Na is bonded to four framework O atoms and two
2
H O molecules. For each water molecule, the one O atom is bonded
2
to two Na atoms, and the two H atoms are hydrogen bonded to
two different O atoms of the structural framework. In other words,
each water molecule forms hydrogen bonds of different strengths
with its local surroundings in the cavity [22–24]. Based on the XRF
Fig. 1. Aluminosilicate framework of zeolites.

1
52
D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
Scheme 3. Mechanism of Natrolite zeolite catalyzed N-formylation of aniline with formic acid.
•
•
•
•
The use of relatively volatile organic solvent [15,48],
Long reaction times [15,48,55],
Harsh reaction conditions [15,48,50,55],
• The use of excess of formic acid which cannot be easily recovered
[17,18,50–53,55,56],
• Recrystallization and column chromatography are required for
The use of relatively high reaction temperature [17,52,53,56],
purification of the products [17,18,48–53,55,56],
Table 3
N-formylation of different amines (1.0 mM) by the Natrolite zeolite and the other reagents.
Entry
Substrate
Formylating method
Conditions
Time (min)
Yield (%)
Ref.
b
◦
C
HCO2H (3 mM), ZnO
SF , 70
60
240
180
120
20
90
79
95
93
96
[17]
[18]
[48]
[47]
Cl
HCO2H (3 mM), PEG-400a
HCO2H (4 mM), HCOONa
SF , r.t.
b
b
1
SF , r.t.
NH2
c
HCO2H (3 mM), Amberlite IR-120
HCO2H (1.2 mM), Natrolite zeolite
MW (320 W)
b
d
SF , r.t.
–
8
5% HCO2H (1.2 mM)
Toluene, reflux
180
720
240
720
210
480
60
720
5760
25
0.0
77
86
90
92
85
93
76
30
83
[45]
[17]
[18]
[49]
[48]
[50]
[47]
[53]
[49]
b
◦
◦
◦
HCO2H (3 mM), ZnO
HCO H (3 mM), PEG-400
HCO2H (3 mM), ZnCl2
HCO2H (4 mM), HCOONa
HCO2H (1.5 mM), Catalyst-free
HCO2H (3 mM), Amberlite IR-120
HCO2H (3 mM), Zinc dust
Methyl formate, bicyclic guanidine
HCO2H (1.2 mM), Natrolite zeolite
SF , 70
C
C
C
NO2
a
b
2
SF , r.t.
b
SF , 70
b
SF , r.t.
2
b
SF , 80
c
MW (320 W)
NH2
b
◦
SF , 70
C
◦
Toluene, 70
C
b
d
SF , r.t.
–
b
◦
C
HCO2H (3 mM), ZnO
SF , 70
60
90
[17]
NH2
3
4
b
HCO2H (4 mM), HCOONa
HCO2H (1.2 mM), Natrolite zeolite
SF , r.t.
420
50
93
92
[48]
–
HO
Cl
b
d
SF , r.t.
HCO2H (3 mM), PEG-400a
SF , r.t.
b
240
86
[18]
MeOH, H2O2, Copper salte
HCO2H (4 mM), HCOONa
HCO2H (3 mM), Amberlite IR-120
Methyl formate, bicyclic guanidine
HCO2H (1.2 mM), Natrolite zeolite
Methanol, r.t.
45
120
70
5760
10
75
98
95
71
90
[46]
[48]
[47]
[51]
b
SF , r.t.
MWc (320 W)
Toluene, r.t.
NH2
Br
b
d
SF , r.t.
–
b
◦
◦
HCO2H (3 mM), ZnO
SF , 70
C
C
20
240
165
80
98
91
99
75
91
[17]
[18]
[48]
[50]
HCO2H (3 mM), PEG-400a
HCO2H (4 mM), HCOONa
HCO2H (1.5 mM), Catalyst-free
HCO2H (1.2 mM), Natrolite zeolite
SF , r.t.
b
b
5
6
SF , r.t.
b
SF , 80
b
d
SF , r.t.
15
–
NH2
HCO NH4 (1.5 mM)
2
CH CN, reflux
3
b
360
360
90
75
150
60
95
120
30
88
42
90
80
85
90
92
94
88
[15]
[18]
[49]
[46]
[48]
[50]
[47]
[51]
HCO2H (3 mM), PEG-400a
SF , r.t.
SF , 70
b
◦
C
HCO2H (3 mM), ZnCl2
MeOH, H2O2, Copper salte
Methanol, r.t.
b
HCO2H (4 mM), HCOONa
SF , r.t.
SF , 80
b
◦
C
HCO2H (1.5 mM), Catalyst-free
HCO2H (3 mM), Amberlite IR-120
Methyl formate, bicyclic guanidine
HCO2H (1.2 mM), Natrolite zeolite
CH NH
2
2
MWc (320 W)
Toluene, r.t.
b
d
SF , r.t.
–
HCO2NH4 (1.5 mmol)
HCO2H (3 mM), ZnO
HCO2H (3 mM), ZnCl2
HCO2H (4 mM), HCOONa
CH2O (3 mM), [Cp*IrI2]2f
Methyl formate, bicyclic guanidine
HCO2H (1.2 mM), Natrolite zeolite
CH3CN, reflux
600
180
360
180
360
60
95
65
60
86
65
97
92
[15]
[17]
[49]
[48]
[52]
[51]
b
◦
◦
SF , 70
C
C
b
SF , 70
O
NH
b
7
SF , r.t.
◦
H2O, 115
C
Toluene, r.t.
b
d
SF , r.t.
25
–
a
Polyethylene glycol-400.
Solvent-free.
Microwave.
Our work.
Copper hydroxyl chloride.
Iridium complexes.
b
c
d
e
f

D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
153
Table 4
Reaction of 2-chloroaniline and formic acid promoted by solid acids.a
Entry
Catalyst
Time (min)
Si/Al ratio
Conversion (%)c
Yield (%)
1
2
3
4
5
␤-Zeolite
Natural zeolite Heulandite
Na-Y
30
30
22
20
20
10
5.0
2.35
1.36
1.36
74
92
100
100
100
61
86
95
96
94
Natrolite zeolite
Natrolite zeoliteb
a
Reaction conditions: formic acid (99% purity, 0.05 mL, 1.2 mmol), zeolite (0.02 g), and amine (1.0 mmol) under solvent-free conditions at room temperature.
Catalyst recovered by filtration.
Monitored by GC and TLC.
b
c
•
•
•
In one method the condition is limited only to the N-formylation
of primary aromatic amines [18],
In one method no N-formylation occurred with para-nitroaniline
comparison with the naturally occurring Lewis acid Natrolite zeo-
lite which is easily attainable.
N-Formylation of amines was performed with HCO H (99%
2
[
48], and
purity) by the Natrolite zeolite without any side reactions, so the
selectivity and conversion of this reaction is 100% (monitored by
GC and TLC), which shows the good activity of the applied catalyst.
The use of ZnCl as a Lewis acid which is homogeneous and cannot
2
easily be recovered and reused [52].
The use of the Natrolite zeolite represents an interesting and
3.8. Characterization of the reaction products
clean synthetic route without application of toxic organic solvents.
Reactions were taken place with mild reaction conditions, easy
operations and cost of the process, risk reduction and high atom
economy which none of the above mentioned disadvantages are
The products were characterized by different spectroscopic
methods. Disappearance of one strong and sharp absorption band
(
NH2 stretching band) and appearance of a carbonyl stretching
observed. The only by-product of this reaction is H O which is a
band in the IR spectra were evidences for the formation of N-formyl
2
safe green solvent. Amines were N-formylated without any side
reactions and no organic solvents were used except for extraction
of the product in the work-up steps. Also, no chromatographic sepa-
ration or crystallization is necessary to obtain the pure compounds.
In addition, the reactions are chemoselective and the high reaction
temperature/pressure and prolonged reaction times are avoided.
derivatives (Supporting Information, Fig. 18). IR spectra showed
−
1
two characteristic peaks, one between 3300 and 3400 cm (sec-
−
1
ondary NH) and the other between 1640 and 1680 cm (N-formyl,
C
O). The relevant 1H NMR spectrum shows two distinctive pro-
ton signals; one is related to NH of the N-formamides and another
belongs to the aldehyde.
3.9. Catalyst reuse and stability
3.7. Activity of the Natrolite zeolite
The reusability of the Natrolite zeolite was checked in the reac-
The key features of zeolites rely on their acid strength, stabil-
ity, selectivity and unique pore dimensions which can control the
selectivity of the reaction.
tion of 2-chloroaniline with formic acid under the present reaction
conditions (Table 2, entry 2). After completion of the reaction, ethyl
acetate was added and the insoluble catalyst was separated by fil-
tration. The catalyst was washed with ethyl acetate several times,
dried and tested for further reactions. Activities of the recovered
catalyst for five consecutive runs are about 96%, 94%, 94%, 93%, and
2%, respectively, which demonstrates the practical recyclability of
this catalyst.
Also, to demonstrate the capability of the catalyst, we tried to
prepare 5-(4-nitrophenyl)amino-1H-tetrazole (C) from the reac-
tion of 4-nitrophenylcyanamide (A) with sodium azide (B) [25].
The catalyst was then recovered from the reaction mixture, washed
with water and ethanol, dried in an oven and reused for the
synthesis of N-(2,4-dimethylphenyl) formamide (F) from the reac-
tion of 2,4-dimethylaniline (D) with formic acid (E). The Natrolite
zeolite was very effective in both reactions and easily recovered
Catalytic property of zeolites is influenced by diffusion of reac-
tants towards the active sites and also the extractability of the
reaction products. This depends upon a number of factors like the
shape of the molecule, volume of the cages, zeolite interactions
and temperature. The shape and size of the guest molecule is very
important in the guest–host interactions. Here we have the same
host (the Natrolite zeolite with Si/Al ratio = 1.36) but the guest
molecules are relatively small (amines and formic acid).
Once the reliability of the applied method confirmed, differ-
ent zeolite catalysts were tested in the reaction of 2-chloroaniline
with formic acid under solvent-free conditions at room tempera-
ture (Table 4). This table indicates that the Natrolite zeolite has the
better catalytic activity over both the ␤-zeolite (Si/Al ratio = 10) and
the Natural zeolite Heulandite (Si/Al ratio = 5.0) which is probably
independent of the polarities of the reactants.
9
(
Scheme 4).
The Si/Al ratios of three zeolites are very important in the N-
formylation of amines and as shown in Table 4, the Natrolite zeolite
is more efficient since the numbers of its Lewis acid sites (Al) are
more. Thus, the reaction is most probably acid-catalyzed.
Also, to determine the reaction mechanism (base or acid-
catalyzed) and to show the advantages of the Natrolite zeolite
3.10. The effect of formic acid on the Natrolite zeolite
The Si/Al ratio was shown to be very important in the acid or base
stability of zeolites. Low-SiO zeolites are fragile in acidic solutions,
2
while high-SiO2 zeolites are completely stable in boiling, concen-
trated mineral acids. However, zeolites with the Si/Al ratio of more
(
with 8-ring channels) in comparison with the Na-Y zeolite (with
2-ring channels), their reactions were compared in the synthe-
1
than 2 (high-SiO zeolites) are unstable in basic solution, while the
2
sis of N-(2-chlorophenyl)formamide. As shown in Table 4, the acid
low ones show increased stability [60].
strength increases at lower SiO /Al O ratio (more Al content), and
Acids are well-known to act as proton-exchangers with the Na-
zeolite. Based upon the data presented (Table 4) we believe that the
proton of formic acid does not exchange with the sodium cation
and forms the Na-formate. These results are consistent with those
2
2
3
so the Natrolite zeolite is a better catalyst. Although a good yield
was obtained using HY zeolite as a synthetic Brønsted acidic zeo-
lite, but its synthetic nature makes it economically undesirable in

1
54
D. Habibi et al. / Journal of Molecular Catalysis A: Chemical 378 (2013) 148–155
O N
2
HN
N
Natrolite zeolite
DMF, 110-115 C, 115 min
A: 4-Nitrophenylcyanamide
B: Sodium azide
Reaction 1: A + B
o
N
N
N
H
Yield: 80 %
C
Me
Recovered Natrolite zeolite
from the reaction 1
r.t., 20 min
Reaction 2: D + E
Me
NHCHO
D: 2,4-Dimethylaniline
E: Formic acid
F
Yield: 91 %
Scheme 4. Capability of the Natrolite zeolite.
reported in the literature for the synthesis of formamides in the
presence of HCOONa. Two reasons confirm this topic:
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