Unexpected Result in the Catalytic Solvent-free Multicomponent Synthesis of 2-Amino-3-cyano-4H-chromene

Full text of DOI:10.1080/00304948.2018.1549903

Organic Preparations and Procedures International
The New Journal for Organic Synthesis
ISSN: 0030-4948 (Print) 1945-5453 (Online) Journal homepage: https://www.tandfonline.com/loi/uopp20
Unexpected Result in the Catalytic Solvent-free
Multicomponent Synthesis of 2-Amino-3-cyano-4H-
chromene
Valeria Palermo, Alexis A. Sosa, Toa S. Rivera, Luis R. Pizzio & Gustavo P.
Romanelli
To cite this article: Valeria Palermo, Alexis A. Sosa, Toa S. Rivera, Luis R. Pizzio & Gustavo
P. Romanelli (2019): Unexpected Result in the Catalytic Solvent-free Multicomponent Synthesis
of 2-Amino-3-cyano-4H-chromene, Organic Preparations and Procedures International, DOI:
10.1080/00304948.2018.1549903
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Organic Preparations and Procedures International, 0:1–13, 2019
# 2019 Taylor & Francis Group, LLC
ISSN: 0030-4948 print / 1945-5453 online
DOI: 10.1080/00304948.2018.1549903
Unexpected Result in the Catalytic Solvent-free
Multicomponent Synthesis
of 2-Amino-3-cyano-4H-chromene
Valeria Palermo, Alexis A. Sosa, Toa S. Rivera, Luis R. Pizzio,
and Gustavo P. Romanelli
ꢀ
Centro de Investigacion y Desarrollo en Ciencias Aplicadas “Dr. Jorge J.
Ronco,” (CINDECA-CCT-CONICET), Universidad Nacional de La Plata,
Calle 47 Nꢀ 257, B1900AJK La Plata, Argentina
Multicomponent reactions (MCRs) are efficient and effective methods for the sustain-
able and diversity-oriented synthesis of heterocycles.1,2 In a green chemistry context,
the traditional methods of performing chemical synthesis are unsustainable, and MCRs
provide an important solution since they are more efficient, cost-effective, and less
wasteful. A known MCR for example is the condensation between aldehyde, malononi-
trile, and phenol or naphthol to give 2-amino-3-cyano-4H-chromenes.3
In this regard, heteropolyacids and derivatives represent one of the most important
categories of solid catalysts. They are widely utilized due to their acid and redox prop-
erties and represent an important family of materials used under heterogeneous and
solvent-free conditions for the synthesis of different heterocycles.4 Keggin, Wells-
Dawson and Preyssler heteropolyacid composites are used in heterocyclic synthesis as
catalysts in several MCRs for the preparation of dihydropyrimidinones,5 quinazoli-
nones,6 pyridines,7 xanthenones,8 imidazoles,9 pyrazoles,10 and 1,4-dihydropyridines.11
Recently, some applications related to the use of zirconia/heteropolyacid composites in
green organic synthesis and relevant technological procedures have been reported.
These include veratrole benzoylation,12 oleochemistry transesterification and esterifica-
tion reactions,13 biomass valorization through the esterification of 2-furoic acid with
alcohols,14 synthesis of bioadditives for biofuels from glycerol esterification with acetic
acid,15 and synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes16 and quinoxalines.17
Moreover, in the last decade, great attention has been paid to 2-amino-3-cyano-4H-
chromenes due to their antimicrobial, antifungal, antioxidant, and pro-apoptotic activ-
ities.18,19 The classical method for their synthesis involves the MCR among aldehydes,
malononitrile, and phenol or naphthol in the presence of a catalyst, such as NaOH,20
Na2CO3,21 Al2O3,22 methanesulfonic acid,3 or heteropolyacid.23
As well, 14-aryl-14H-dibenzo[a,j]xanthenes have attractive biological properties
such as antiviral, anti-inflammatory, antibacterial, and antimicrobial activity, among
Received January 23, 2017; in final form August 25, 2018.
ꢀ
Address correspondence to Gustavo P. Romanelli, Centro de Investigacion y Desarrollo en
Ciencias Aplicadas “Dr. Jorge J. Ronco,” Universidad Nacional de La Plata, Calle 47 Nꢀ 257,
B1900AJK La Plata, Argentina. E-mail: gpr@quimica.unlp.edu.ar
1

2
Romanelli et al.
Scheme 1. Multicomponent reaction among benzaldehyde, malononitrile and 2-naphthol.
others.24,25 They can be synthesized from 2-naphthol and benzaldehyde in the presence
of an acid catalyst such as bulk26 and supported16 heteropolyacids, PEG-OSO3H,24
BTMA-Br3,25 p-toluenesulfonic acid,27 P2O5/Al2O3,28 and ionic liquids.29
In this article, we present a study of the MCR among benzaldehyde, malononitrile,
and 2-naphthol, catalyzed by zirconia/phosphotungstic acid composites, to obtain 2-
amino-3-cyano-4H-chromene (4) or 14-aryl-14H-dibenzo[a,j]xanthene (5) depending on
the reaction conditions (Scheme 1). The unexpected result of obtaining a xanthene in
the chromene synthesis is related to the report by Heravi and coworkers for the synthe-
sis of dihydropyrano[3,2-c]chromene.30 They found that when a Keggin heteropolyacid
was used as catalyst, bis-coumarin was obtained as the main product. We examined the
MCR of benzaldehyde, malononitrile and 2-naphthol (Method A) at different tempera-
tures and molar ratios of substrates. The reaction conversion and selectivity were eval-
uated using the prepared catalysts under solvent-free conditions. In general, and as
reported by Heravi, the reaction using a Preyssler bulk catalyst in acetonitrile or water
produces the corresponding 2-amino-3-cyano-4H-chromenes.23 However, when our cat-
alysts, based on phosphotungstic acid in a mesoporous zirconia framework, were used,
an unexpected mixture of 4 and 5 was detected.
Initially, a non-active phase experiment using benzaldehyde, malononitrile and 2-
naphthol (1:1:1) (Table 1, entry 1) was tested. It was observed that the conversion was
low (25%), and the selectivities for i (2-benzylidenemalononitrile formed by condensa-
tion of benzaldehyde and malononitrile), 4 and 5 were 31%, 29% and 40% respectively.
When the reaction was performed at 100 ꢀC, no reaction was observed (Table 1, entry
6). Similarly, in the absence of any catalyst, the conversion was only 5% (Table 1, entry
10).
The catalytic activity of ZrPTA60 was then tested. After 3 h at 130 ꢀC the conver-
sion increased up to 68% (Table 1, entry 2). However, the selectivity was low and the
three products detected in the blank experiment were again observed (i ¼ 12%, 4 ¼
34% and 5 ¼ 52% respectively).
Another key factor is the molar ratio of reactants. Table 1, entries 2, 3, and 4,
shows the results when an excess of benzaldehyde was added. Equimolar quantities of
the substrates gave a conversion of 68%, but an excess of benzaldehyde (ratio 1.3:1
with respect to the other substrates) improved the conversion to 100% (Table 1, entries
4) giving the best performance.
The influence of temperature on the reaction conditions is presented in Table 1,
entries 3, 7, 8, and 9. Four experiments were performed (at 130, 110, 100 and 80 ꢀC).
No reaction was detected when the test was performed at 80 ꢀC (Table 1, entry 9) and
low conversions were observed at 110 and 100 ꢀC (32% and 20% respectively, Table 1,
entries 7 and 8). The best conversion, for the molar ratio 1:1:1.2, was achieved at
130 ꢀC (80%, Table 1, entry 3).

2-Amino-3-cyano-4H-chromene
3
Table 1
Temperature and Molar Ratio Study in the Multicomponent Reaction between
Benzaldehyde, Malononitrile, and 2-naphthol Using Method A
Entry Catalyst Temp. (ꢀC) t. (h) Ratioa Conv. (%) i (%) 4 (%) 5 (%) Other (%)
1
2
3
4
5
6
7
8
ZrPTA00
ZrPTA60
ZrPTA60
ZrPTA60
ZrPTA60
ZrPTA00
ZrPTA60
ZrPTA60
ZrPTA60
–
130
130
130
130
130
100
110
100
80
5
3
3
3
5
5
3
3
1:1:1
25
68
80
100
100
–
31
12
5
29
34
36
42
40
–
40
52
55
56
54
–
–
2
4
2
4
–
–
–
–
–
1:1:1.1
1:1:1.2
1:1:1.3
1:1:1.2
1:1:1
–
–
–
1:1:1.2
1:1:1.2
32
20
–
–
–
100
100
–
–
–
9
10
10 1:1:1.2
1:1:1
–
–
130
5
5
30
30
40
Experimental conditions: benzaldehyde (1-1.3 mmol), malononitrile (1 mmol), 2-naphthol
(1 mmol), catalyst (85 mg, 0.18 mmol of active phase), temperature (130-80 ꢀC), time (3-10 h),
solvent-free, stirring.
aMolar ratio of malononitrile to 2-naphthol and to benzaldehyde.
Table 2
Alternative Methods to Prepare 2-amino-3-cyano-4H-chromene (4) or 14-phenyl-14H-
dibenzo[a,j]xanthene (5)
Entry Catalyst Method T (ꢀC) t. (h) Conv. (%) i (%) 4 (%) 5 (%) Other (%)
1
2
3
4
5
6
7
8
9
ZrPTA00 A
ZrPTA60 A
ZrPTA30 A
ZrPTA60 A
ZrPTA60 B
ZrPTA30 B
ZrPTA60 B
ZrPTA60 B
ZrPTA60 B
ZrPTA60 C
130
130
130
100
130
130
110
100
90
3
3
3
3
3
3
3
3
3
1
32
100
80
15
100
85
50
–
20
42
39
–
30
56
61
100
37
46
31
32
–
–
2
–
–
1
–
2
–
–
4
–
–
–
62
54
67
68
–
–
100
20
–
–
–
–
10
130
100
–
–
96
Method A: benzaldehyde (1.3 mmol), malononitrile (1 mmol), 2-naphthol (1 mmol), catalyst
(85 mg: 0.009 or 0.018 mmol of active phase), temperature (130-100 ꢀC), time (3 h), solvent-
free, stirring.
Method B: 2-benzylidenemalononitrile (1 mmol), 2-naphthol (1 mmol), catalyst (85 mg:
0.009 or 0.018 mmol of active phase), temperature (130-90 ꢀC), time (3 h), solvent-free, stirring.
Method C: benzaldehyde (1.2 mmol), 2-naphthol (2 mmol), catalyst (85 mg: 0.018 mmol of
active phase), temperature (130 ꢀC), Time (1 h), solvent-free, stirring.
From the results presented in Table 1, it can be seen that the best reaction condi-
tions required to obtain 100% conversion were: benzaldehyde (1.3 mmol); malononitrile
(1 mmol); 2-naphthol (1 mmol); catalyst (85 mg, 0.018 mmol active phase); 3 h, 130 ꢀC
stirring, under solvent-free conditions. Under these conditions, the selectivity of prod-
ucts was: 42% (4) and 56% (5) (Table 1, entry 4).

4
Romanelli et al.
Table 3
ZrPTA60 Catalyst Reuse
Entry
Cycle
Use
1st Reuse
2nd Reuse
3rd Reuse
Con. (%)
4 (%)
5 (%)
1
2
3
4
100
100
99
62
60
61
60
37
37
38
37
99
Experimental conditions: 2-benzylidenemalononitrile (1 mmol), 2-naphthol (1 mmol), catalyst
(85 mg: 0.018 mmol of active phase), temperature (130 ꢀC), time (3 h), solvent-free, stirring.
Based on these results, we started two alternative studies to optimize the selectivity
for 4 and 5. Using the best conditions obtained for the reaction (Table 1, entry 4), add-
itional tests were carried out with the catalysts ZrPTA30 and ZrPTA60. The results are
listed in Table 2. In the absence of PTA in the catalyst, low conversion (32%, Table 2,
entry 1) was observed at 130 ꢀC even at a reaction time of 3 h. In this case, a relative
selectivity of product i (50%) was detected. When we used the catalyst containing PTA
as active phase, the substrate conversion increased notably for the reaction performed
at 130 ꢀC.
The sample with the highest PTA content (ZrPTA60) showed the best conversion
(Table 2, entry 2). On the other hand, the conversion obtained using ZrPTA30 (Table 2,
entry 3) was slightly lower, which could be attributed to the lower acidity of this cata-
lyst. However, although conversions were high (100% and 80%), the two products 4
and 5 with comparable selectivity were always obtained (Table 2, entries 2 and 3).
The results using Method A suggest that high temperatures (130 ꢀC) are necessary
for a relevant conversion of substrates; nevertheless, the formation of 5 is always
important. For this reason, we performed some additional experiments (Method B).
These experiments were carried out in two steps in order to improve the selectivity for
4. The putative mechanism involves the reaction between benzaldehyde and malononi-
trile to form 2-benzylidenemalononitrile, which then reacts with 2-naphthol to give 4.31
In Method B, we expected that the absence of benzaldehyde would inhibit the formation
of 5, because its formation requires the presence of an equivalent of benzaldehyde.
2-Benzylidenemalononitrile was prepared following a procedure reported in the lit-
erature.32 Afterwards, the catalytic activity of ZrPTA30 and ZrPTA60 was studied in
the reaction. The results are listed in Table 2, entries 5 and 6. Similarly to Method A,
high conversion was achieved with the two catalysts, and 4 and 5 were always obtained
with comparable selectivity despite not having benzaldehyde in the reaction medium.
However, the selectivity towards the formation of 4 was substantially greater than that
obtained by Method A (see Table 2, entry 2: ratio 4:5 42:56%, and entry 5: ratio 4:5
62:37%; in both cases the conversion was 100%). The appearance of benzaldehyde,
necessary for the formation of product 4, in the reaction medium can be rationalized
since the formation of 2-benzylidenemalononitrile is reversible. To improve the select-
ivity for 4 we performed three additional experiments at temperatures lower than
130 ꢀC (Table 2, entries 7-9).
The results show the best conversion and selectivity of 4 were achieved with
Method B at 110 ꢀC (100% and 67% respectively, Table 2, entry 7). In this case, the
ratio between 4 and 5 was the highest. However, it was impossible to inhibit the forma-
tion of 5 completely. On the other hand, no reaction was detected when the test was

2-Amino-3-cyano-4H-chromene
5
Table 4
Chromene and Xanthene Selectivity Using Different Aldehydes for the
Alternative Methods
Entry
Aldehyde
Method t. (h) Chromene (%) Xanthene (%) Other (%)
1
2
3
4
5
6
7
8
A
B
C
A
B
C
A
B
C
A
B
C
A
B
C
3
3
1
3
3
1
3
3
1
3
5
2
3
4
2
42
67
–
56
31
96
54
30
94
52
29
93
58
27
98
56
27
96
2
2
4
4
4
6
8
6
7
2
3
2
4
2
4
42
66
–
40
65
–
9
10
11
12
13
14
15
40
70
–
40
71
–
Method A: substituted benzaldehyde (1.3 mmol), malononitrile (1 mmol), 2-naphthol
(1 mmol), ZrPTA60 (85 mg: 0.018 mmol of active phase), temperature (130 ꢀC), time (3 h), solv-
ent-free, stirring.
Method B: substituted 2-benzylidenemalononitrile (1 mmol), 2-naphthol (1 mmol), ZrPTA60
(85 mg: 0.018 mmol of active phase), temperature (110 ꢀC), time (3 h), solvent-free, stirring.
Method C: substituted benzaldehyde (1.2 mmol), 2-naphthol (2 mmol), ZrPTA60 (85 mg:
0.018 mmol of active phase), temperature (130 ꢀC), Time (1 h), solvent-free, stirring.
performed at 90 ꢀC (Table 2, entry 9) and low conversion values were observed at
100 ꢀC (20%; Table 2, entry 8).
Selective preparation of 14-aryl-14H-dibenzo[a,j]xanthenes was reported previously
by our research group16 and involved the pseudo MCR between an aldehyde and 2
equivalents of 2-naphthol at 130 ꢀC, under solvent-free conditions using ZrPTA60 as
catalyst (Table 2, entry 10, Method C).
To study the reusability of the catalyst, once the reaction was completed the cata-
lyst was filtered, washed with toluene and dried in vacuo. The results are given in
Table 3 and suggest no appreciable variations when the catalyst is reused four consecu-
tive times.
The scope and generality of the three Methods are illustrated for different alde-
hydes, using ZrPTA60 as catalyst. The results are summarized in Table 4, and show
that a major selectivity toward the corresponding xanthene is achieved with Method A
at 130 ꢀC, meanwhile the chromene selectivity increased when the reaction was per-
formed in two steps at 110 ꢀC. The conversion was 100% for all the tested aldehydes.
A plausible reaction mechanism is given in order to justify the formation of both prod-
ucts. Scheme 2 shows the reaction mechanism for the formation of 4 assisted by phospho-
tungstic acid included in a mesoporous zirconia catalyst and involves the MCR among
benzaldehyde, malononitrile, and 2-naphthol (Path A). Meanwhile, a plausible mechanism
for the formation of 5 involves the pseudo MCR between 1 equivalent of benzaldehyde
(Path B), resulting from the hydrolysis of i, and two equivalents of 2-napththol.

6
Romanelli et al.
Scheme 2. Plausible mechanism for the concurrent formation of 4 and 5.
In conclusion, the prepared materials were examined as reusable catalysts, under
solvent-free conditions, for the MCR among benzaldehyde, malononitrile, and 2-naph-
thol. Different reaction variables such as catalyst, temperature, molar ratio of reactants
and procedure were investigated in order to probe the selectivity to 4 and 5. Compound
5 was the main product formed at 130 ꢀC in the MCR in Method A. The yield of prod-
uct 4 can be increased by performing the reaction in two stages: (1) formation of 2-ben-
zylidenemalononitrile and (2) reaction of 2-benzylidenemalononitrile with 2- naphthol.
However, the formation of product 5 can never be completely inhibited. In Method B
the catalyst was reused in four consecutive runs, and no appreciable loss of its catalytic
activity was observed. To the best of our knowledge, this is the first report showing
that 5 is formed as a major product in the MCR synthesis of 4.

2-Amino-3-cyano-4H-chromene
7
Experimental Section
All chemical reagents and solvents were obtained from Aldrich and were used without
further purification. All products are known compounds and were identified by com-
parison of their physical and spectral data with those of authentic samples. Melting
1
points were measured on Bioamerican Bs 448 apparatus and were uncorrected. H-
NMR and 13C-NMR spectra were recorded on a Varian Mercury Plus 200 and a Bruker
Advance DPX-400.
Synthesis and Characterization of Zirconia/Phosphotungstic Acid Composites
The samples were synthesized following the procedure previously described by Rivera
et al.,16 using a higher thermal treatment temperature. Zr(OPr)4 (7.97 g) was mixed with
absolute ethanol (57.5 g) and stirred for 15 min to obtain a homogeneous solution at room
temperature. Then, 0.16 mL of 0.28 M HCl aqueous solution was dropped slowly into the
above mixture to catalyze the sol-gel reaction. After 3 h, 0.30 g of polyethylene glycol
(PEG, used as nonsurfactant pore-forming agent) was added to the hydrolyzed solution
under vigorous stirring together with 20 mL of a tungstophosphoric acid (H3PW12O40) solu-
tion, whose concentration was varied in order to obtain a H3PW12O40 (PTA) concentration
of 30% and 60% w/w in the solid (ZrPTA30 and ZrPTA60 respectively). The gels were
then kept in a beaker at room temperature up to dryness. The solids were ground into pow-
der and washed with distilled water for 24 h, in a system with continuous stirring, to
remove PEG. Afterwards, they were calcined at 250 ꢀC for 24 h.
The solids were characterized by Fourier transform infrared (FT-IR), and 31P magic
angle spinning-nuclear magnetic resonance (31P MAS-NMR). Their acidic and textural
properties were determined by means of potentiometric titration with n-butylamine and
from the N2 adsorption–desorption isotherms at the liquid-nitrogen temperature.
The specific surface area and the mean pore diameter of the solids were determined
from the N2 adsorption–desorption isotherms at the liquid–nitrogen temperature,
obtained using Micromeritics ASAP 2020 equipment. The solids were previously
degassed at 100 ꢀC for 24 h. The 31P MAS-NMR spectra were recorded with Bruker
1
Avance II equipment, using the CP/MAS H–31P technique. A sample holder of 4 mm
diameter and 10 mm in height was employed, using 5 s pulses, a repetition time of 4 s,
and working at a frequency of 121.496 MHz for 31P at room temperature. The spin rate
was 8 kHz, and several hundred pulse responses were collected. Phosphoric acid 85%
was employed as external reference. The FT-IR spectra of the solids were obtained
using a Bruker IFS 66 FT-IR spectrometer and pellets in KBr in the 400–4000 cmꢁ1
wavenumber range. The acidity of the solids was estimated by means of potentiometric
titration. A known mass of solid was suspended in acetonitrile and stirred for 3 h. Then,
the suspension was titrated with 0.05 N n-butylamine in acetonitrile using Metrohm 794
Basic Titrino apparatus with a double junction electrode.
The specific surface area (SBET) of ZrPTA30 and ZrPTA60 samples determined
from the N2 adsorption–desorption isotherms using the Brunauer–Emmett–Teller (BET)
method, and the micropore specific surface area (SMicro) estimated from the t-plot
method are listed in Table 5. The obtained isotherms can be classified as type IV and
showed the main characteristics assigned to mesoporous materials (Figure 1).
The 31P MAS-NMR spectra of the ZrPTA30 and ZrPTA60 samples (Figure 2) dis-
played two wide bands with maximum at around - 14.3 and - 13.5 ppm, which were

8
Romanelli et al.
Table 5
Relevant Characteristics of Synthesized Catalysts
31P MAS-NMR (ppm) SBET (m2/g) SMicro (m2/g) Ei (mV) NA
a
b
Sample
ZrPTA00
–
279
230
205
–
167
401
425
–
ZrPTA30 ꢁ14.3 and ꢁ13.6
35
28
186
238
ZrPTA60 ꢁ14.4 and ꢁ13.5
aMicropore specific surface area estimated by the t plot method.
bNumber of acid sites expressed as meq n-butylamine/g.
attributed to [PW12O40]3ꢁ anion and to the [P2W21O71]6ꢁ dimeric species, respectively.33
The line width increase and the downfield shift compared to the PTA ( ꢁ15.3 ppm) were
assigned to the interaction between the anion and the zirconia matrix.34
The FT-IR spectra displayed the P–O, W–O, and W–O–W stretching vibrations of
the [PW12O40]3ꢁ anion overlapped with the zirconia wide band due to Zr–O stretching
vibration (Figure 3). The main FT-IR bands of the dimer [P2W21O71]6ꢁ assigned to the
stretching vibrations P-O, W-O, W-O-W appear at similar wavenumber values to those
reported for the characteristic [PW12O40]3ꢁ anion,35 making it difficult to establish their
presence on the basis of these spectra. On the other hand, the absence of characteristic
signals of PEG, such as the strong C-O stretching band at 1094 cmꢁ1, confirm that this
36
compound was completely removed by washing with distilled water.
Potentiometric titration with n-butylamine revealed that the acid strength of
ZrPTA30 (Ei ¼ 401 mV) and ZrPTA60 (Ei ¼ 425 mV) samples was noticeably higher
than that of the unmodified zirconia ZrPTA00 (Ei ¼ 190 mV) but lower than that of
bulk PTA (Ei ¼ 620 mV).37 In agreement with this previous work, the lower acid
strength of the ZrPTA30 and ZrPTA60 samples compared to bulk PTA could be given
by the presence of the protons as Hþ(H2O)2 species in the H3PW12O40ꢂ6H2O. Whereas
in the ZrPTAXX samples, these species interacted with the oxygen of Zr–OH groups,
or in a higher hydration state (Hþ(H2O)n). On the other hand, the number of acid sites
(NA), as the area under the curve, increased with the increment of the PTA content:
ZrPTA30 < ZrPTA60 (238 and 186 meq n-butylamine/g, respectively).
The PTA content in the samples was estimated as the difference between the W
amount contained in the tungstophosphoric acid solution originally used for the impreg-
nation and the amount of W that remained in the water solutions after removing the
PEG. The amount of W in the obtained solutions was determined by atomic absorption
spectrometry using a Varian AA Model 240 spectrophotometer. The calibration curve
method was used with standards prepared in the laboratory. The analyses were carried
out at a wavelength of 254.9 nm, bandwidth 0.3 nm, lamp current 15 mA, phototube
amplification 800 V, burner height 4 mm, and acetylene–nitrous oxide flame (11:14).
Typical Catalytic Test
Method A: a mixture of benzaldehyde (1.3 mmol), 2-naphthol (1 mmol), malononitrile
(1 mmol) and the catalyst (0.9% and 1.8% mmol active phase) was stirred at a deter-
mined temperature (130, 110, 100, and 80 ꢀC) for the appropriate time.
Method B: a mixture of 2-benzylidenemalononitrile (1 mmol), 2-naphthol (1 mmol),
and the catalyst (0.9% and 1.8% mmol active phase) was stirred at a determined

2-Amino-3-cyano-4H-chromene
9
Figure 1. N2 adsorption–desorption isotherms of ZrPTA00, ZrPTA30, and ZrPTA60 samples.
Adsorption branch (full symbols), desorption branch (open symbols).
temperature (130, 110, 100, and 90 ꢀC) for the appropriate time. After the reaction, the
catalyst was filtered, washed thoroughly with toluene, dried in a vacuum oven (20 ꢀC, 4 h)
and reused for the next reaction, following the procedure described earlier.
Method C: 14-aryl-14H-dibenzo[a,j]xanthene was synthesized as previ-
ously reported.16
The completion of the reactions was determined by thin layer chromatography on
silica gel (hexanes:ethyl acetate 4:1). The reaction mixture was cooled to 20 ꢀC, toluene
(5 mL) was added, and then the mixture was stirred for 15 min and filtered to separate
the catalyst, which was subsequently washed twice with toluene (3 mL). The combined
toluene extracts were washed twice with water (5 mL), dried over anhydrous Na2SO4,
and evaporated in vacuo. The products were separated by liquid column chromatog-
raphy (silica gel 60, mixtures of hexanes/ethyl acetate 4:1 to 3:1) and recrystallized
from ethanol to afford the pure chromene and xanthene.
NMR Spectra of Compounds
2-Benzylidenemalononitrile (i): mp. 80-82 ꢀC, lit. mp. 82 ꢀC.32 1H-NMR (CDCl3,
200 MHz): d 7.53-7.56 (m, 2H), 7.62-7.65 (m, 1H), 7.78 (s, 1H), 7.90-7.92 (2H, m).
13C-NMR (CDCl3, 50 MHz): d 81.3, 113.5, 127.8, 128.4, 128.7, 131.5, 159.9.

10
Romanelli et al.
Figure 2. 31P MAS-NMR spectra of PTA, ZrPTA30, and ZrPTA60 samples.
2-Amino-3-cyano-4-phenyl-4H-chromene (4): mp. 277-278 ꢀC, lit. mp. 280 ꢀC.23
1H-NMR (DMSO-d6, 200 MHz): d 5.29 (s, 1H), 7.02 (s, 2H), 7.14-7.29 (m, 5H), 7.32-
7.44 (m, 3H), 7.86-7.98 (m, 3H). 13C-NMR (DMSO-d6, 50 MHz): d 38.7, 58.6, 116.4,
117.5, 121.0, 124.2, 125.5, 127.1, 127.8, 127.6, 128.9, 129.2, 129.9, 120.8, 131.4,
145.4, 148.4, 160.3.
14-Phenyl-14H-dibenzo[a,j]xanthene (5): mp. 181-182 ꢀC, lit. mp. 181-182 ꢀC.24
1H-NMR (CDCl3, 200 MHz): d 6.45 (s, 1H), 7.13-7.18 (d, 2H, J ¼ 8 Hz), 7.25-7.30
(4H, m), 7.40-7.59 (m, 9H), 7.71-7.74 (d, 2H, J ¼ 8 Hz). 13C-NMR (CDCl3, 50 MHz):
d 31.8, 115.5, 116.4, 119.2, 123.1, 124.8, 126.7, 128.2, 129.5, 130.1, 132.3, 136.8,
141.5, 148.2, 149.8.
2-Amino-3-cyano-4-(4-methylphenyl)-4H-chromene: mp. 265-267 ꢀC, lit. mp.
270-271 ꢀC.38 1H-NMR (DMSO-d6, 400 MHz): d 2.20 (s, 3H), 5.18 (s, 1H), 6.30 (bs,
2H), 7.10 (m, 4H), 7.32 (d, 1 H, J ¼ 8.6 Hz), 7.34 (d, 2H, J ¼ 5.1 Hz), 7.70 (t, 1H, J ¼
5.7 Hz), 7.82 (d, 2 H, J ¼ 8.7 Hz). 13C-NMR (DMSO-d6, 100 MHz): d 20.8, 39.3, 58.6,
116.3, 117.4, 121.0, 124.2, 126.5, 127.5, 128.9, 129.8, 129.9, 130.7, 131.4, 136.2,
143.4, 147.4, 160.3.
14-(4-Methylphenyl)-14H-dibenzo[a,j]xanthene: mp. 228-229 ꢀC, lit. mp. 224-
226 ꢀC.25 1H-NMR (CDCl3, 200 MHz): d 2.15 (s, 3H), 6.37 (s, 1H), 6.92 (d, 2H, J¼
9.5 Hz), 7.30-7.78 (m, 12H), 8.33 (d, 2H, J¼ 9.4Hz). 13C-NMR (CDCl3, 50 MHz): d
19.2, 35.2, 115.8, 116.3, 121.3, 122.8, 125.3, 126.5, 127.6, 129.3, 129.3, 129.4, 129.5,
134.0, 140.8, 146.6.
2-Amino-3-cyano-4-(4-methoxyphenyl)-4H-chromene: mp. 188-190 ꢀC, lit. mp.
189-190 ꢀC.21 1H-NMR (DMSO-d6, 400 MHz): d 3.72 (s, 3H), 5.16 (s, 1H), 5.63 (m,

2-Amino-3-cyano-4H-chromene
11
Figure 3. FT-IR spectra of ZrPTA00, ZrPTA30, ZrPTA60, and PTA.
2H), 6.78 (bs, 2H), 7.11 (d, 2H, J ¼ 8.5 Hz), 7.30 (d, 2H, J ¼ 8.5 Hz), 7.40 (m, 2H),
7.70 (t, 1H, J ¼ 7.3 Hz), 7.78 (d, 1H, J ¼ 8.6 Hz). 13C-NMR (DMSO-d6, 100 MHz): d
42.1, 60.2, 63.5, 119.2, 121.2, 121.9, 125.8, 129.0, 130.2, 132.2, 133.3, 133.7, 134.6,
135.4, 136.3, 144.4, 152.1, 163.2, 165.7.
14-(4-Methoxyphenyl)-14H-dibenzo[a,j]xanthene: mp. 202-204 ꢀC, lit. mp. 203-
204 ꢀC.24 1H-NMR (CDCl3, 200 MHz): d 3.55 (s, 3H), 6.42 (s, 1H), 6.64 (d, 2H,
J ¼ 9.6Hz), 7.30-7.82 (m, 12H), 8.35 (d, 2H, J ¼ 9.6 Hz). 13C-NMR (CDCl3, 50 MHz):
d 36.5, 53.1, 114.3, 117.4, 118.5, 123.6, 124.2, 127.3, 128.1, 129.2, 129.5, 131.5,
133.8, 137.4, 149.1, 158.1.
2-Amino-3-cyano-4-(4-flourophenyl)-4H-chromene: mp. 228-230 ꢀC, lit. mp. 229-
230 ꢀC.39 1H-NMR (DMSO-d6, 400 MHz): d 5.30 (s, 1H), 7.18 (bs, 2H), 7.12 (m, 2H),
7.22 (m, 2H), 7.38 (d, 1H, J ¼ 8.6 Hz), 7.44 (m, 2H), 7.84 (d, 2H, J ¼ 8.6 Hz), 7.91
(m, 2H). 13C-NMR (DMSO-d6, 100 MHz): d 38.4, 58.1, 116.0, 116.9, 120.5, 123.6,
124.9, 127.2, 128.5, 128.8, 129.6, 130.1, 130.8, 141.9, 146.8, 159.8, 162.8.
14-(4-Flourophenyl)-14H-dibenzo[a,j]xanthene: mp. 239-240 ꢀC, lit. mp. 233-
236 ꢀC.25 1H-NMR (CDCl3, 400 MHz): d 6.45 (s, 1H), 6.75-7.84 (m, 2H), 7.37-7.61
(m, 8H), 7.77-7.88 (m, 4H), 8.35 (d, 2H, J ¼ 8.0 Hz). 13C-NMR (CDCl3, 100 MHz): d
37.2, 115.1, 115.6, 117.1, 118.0, 122.5, 124.4, 126.9, 128.9, 129.0, 129.6, 129.7, 131.1,
131.3, 140.8, 140.8, 148.7.
2-Amino-4-(4-chlorophenyl)-3-cyano-4H-chromene: mp. 212-214 ꢀC, lit. mp. 206-
208 ꢀC.23 1H-NMR (DMSO-d6, 400 MHz): d 5.10 (s, 1H), 7.10 (bs, 2H), 7.18 (s, 2H),
7.27 (d, 2 H, J ¼ 8.5 Hz), 7.37 (d, 2H, J ¼ 8.5 Hz), 7.59 (m, 2H), 7.88 (d, 1H, J ¼
8.5 Hz), 8.25 (d, 1H, J ¼ 8.5 Hz). 13C-NMR (DMSO-d6, 100 MHz): d 39.9, 58.1,
115.7, 117.3, 120.8, 122.9, 125.4, 127.7, 128.9, 129.3, 130.3, 130.5, 131.3, 132.7,
145.2, 147.3, 160.3.

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Romanelli et al.
14-(4-Chlorophenyl)-14H-dibenzo[a,j]xanthene: mp. 288-290 ꢀC, lit. mp. 286-
287 ꢀC.24 1H-NMR (CDCl3, 200 MHz): d 6.44 (s, 1H), 7.08-8.32 (m, 16H). 13C-NMR
(CDCl3, 50 MHz): d 37.4, 116.8, 118.2, 122.5, 125.4, 126.9, 128.7, 129.0, 129.5, 129.6,
131.1, 131.3, 132.0, 143.5, 148.7.
Acknowledgments
The authors are grateful to CONICET (PIP 003), UNLP (X732) and ANPCYT (0409)
for financial support. The authors thank L. Osiglio, G. Valle, and E. Soto for the meas-
urements of acidic properties, FT-IR, and SBET
.
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