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H. Zhu et al. / Journal of Catalysis 374 (2019) 217–229
and the yields significantly dropped to 57% and 32%, respectively
(Table S3, entries 4 and 8). The reaction time was extended to
12 h, however, the reaction yields were not apparently improved
in these cases (Table S3, entries 5 and 9). Besides, only the moder-
ate yields of product were produced when increasing the ratio of
substrate (Table S3, entries 6–7). Increasing the amount of catalyst
to 15 mol% resulted in a slightly increase in the yield of product
(Table S3, entry 10). Hence, the optimal fiber catalyst to substrate
ratio (0.01 mmol of active prolinamide moiety per mmol aldehyde)
was found to be effective for the reaction. Additionally, a variety of
organic solvents were also screened in the model reaction. It was
observed that the strong polar solvents such as methanol and etha-
nol gave moderate to high yield of 87% and 45%, respectively
(Table 3, entries 8–9). When solvent polarities were below ethanol,
the reaction failed to take place. This result indicated that the sol-
vent plays an important role in the reaction. We then performed
solvent uptake test of fiber catalyst PANPAÀ2F in various solvents
to evaluate its swollen capacity. Recent studies have shown that
good swelling properties of support in solvent make the catalytic
sites flexible and accessible, which like their homogeneous coun-
terparts (quasi-homogeneous) enhances the catalytic performance
[47]. As shown in Table S4, the solvent uptake of fiber catalyst in
other organic solvents was much lower than that in methanol
and ethanol. The low swollen capacity of fiber catalyst would cause
the poor disperse of catalytic sites in solvent and the limited com-
patibility of solvents with fiber catalyst hampered the contact
between reactants and catalytic site, thereby, causing reaction fail
to take place.
With the optimized reaction conditions in hand (Table 3, entry
4), we then set out to investigate the scope and generality of this
method, and the results are shown in Table 4. We are glad to
observe that the reactions of various substituted benzaldehydes
with ethyl cyanoacetate all proceeded efficiently and the desired
products were obtained in good to excellent yields. Aromatic alde-
hydes bearing electron-withdrawing groups were more reactive
and reacted at a faster rate than those with electron-donating
groups (Table 4, entries 2–6 vs 7–14). In addition to above ben-
zaldehydes, the reaction was also carried out smoothly using other
aldehydes such as 1-naphthaldehyde and heteroaromatic aldehy-
des, and provided excellent yields of products (Table 4, entries
15–17). Different nucleophiles were also evaluated. Compared to
reactions of aromatic aldehydes with ethyl cyanoacetate, the reac-
tions of malononitrile with aromatic aldehydes were more efficient
and gave almost quantitative yields in short time (Table 4, entries
18 and 19). This may be attributed to the high active methylene
group of malononitrile. Notably, benzoyl acetonitrile, although its
activity was lower than the other two nucleophiles, could readily
react with aromatic aldehydes under heating condition and afford
the corresponding products in 98% and 94% yields (Table 4, entries
20 and 21). Moreover, ketones which usually recognized as inac-
tive carbonyl compounds were also examined (Table 4, entries
22–25). The reactions of cyclohexanone and isatin with malononi-
trile both performed well and desired products were obtained in
high yields with this method (Table 4, entries 22 and 25). All the
above results clearly demonstrated that the designed fiber catalyst
PANPAÀ2F showed excellent performance in the Knoevenagel
reaction.
derivatives, we intended to investigate their synthesis using a sim-
ple, efficient and environmentally friendly method.
Initially, the model reaction of benzaldehyde, malononitrile and
resorcinol was performed in water at 50 °C with PANPAÀ2F as cata-
lyst and the target product 12a was obtained in 62% yield accom-
panied by the formation of a little of Knoevenagel product 8r
(Table S5, entry 1). When the reaction was conducted in the pres-
ence of original PANF, no target product was detected while a cer-
tain amount of Knoevenagel product was obtained (Table S5, entry
2). This result indicated that the prolinamide moiety acted as cat-
alytic sites to ensure the conversion of Knoevenagel intermediate
to target product. Further increase in the temperature and found
that the yield of 12a reached up to 95% with PANPAÀ2F at 80 °C
for 1 h (Table S5, entries 3–5). When the reaction was carried out
with 8 mol% amount of catalyst, the target product was produced
in 93% yield after 2 h (Table S5, entries 7).The use of 5 mol% of cat-
alyst led to apparently slow reaction and the yield of 12a declined
from 95% to 70% (Table S5, entry 6) and increasing the amount of
substrate did not play effective role (Table S5, entries 8–11). And
the catalyst loading of 12 mol% slightly improved the yield
(Table S5, entry 12). Hence, 10 mol% was found to be optimal cat-
alyst loading. Moreover, other prepared fiber catalysts were also
evaluated in reaction under the identical condition. A low yield
of 12a was obtained when the PANPAF was used as catalyst, in
which a certain amount of Knoevenagel product was detected
(Table S5, entry 13). Compared with PANPAÀ2F, PANPAÀ3F show
the similar catalytic activity and gave
a high yield of 93%
(Table S5, entry 14). Excellent yields of target product could be
obtained when PANPAÀ2F combining with additional hydrophobic
groups (Table S6, entries 3–4). However, with PANTPAÀ2F-IL and
PANTPAÀ3F-IL as catalysts, the reactions proceeded sluggishly and
the yields of target product dropped to 52% and 58%, respectively
(Table S5, entries 15–16). And much lower yields were obtained
with higher loading of PANTPAÀ2F-IL (Table S6, entries 1–2). These
results demonstrate that length of carbon chain and linker group
actually affect the reactivity. The good performance of PANPAÀ2F
was due to the flexible dispersion of catalytic sites and the formed
hydrophobic surface microenvironment, which both synergisti-
cally made the reactants more accessible to catalytic sites and
thereby accelerated the reaction. In addition, the effect of solvents
was studied and the results are shown in Table S7. It can be seen
that polar solvents such as methanol, ethanol, acetonitrile and var-
ious low polar solvents show no superiority to water and the Kno-
evenagel intermediate was major product in these cases (Table S7,
entries 1–2 and 6–10). Mixed solvents with different ratios of
water to ethanol were also employed in the reaction and found
that higher yield of 12a was obtained when gradually increased
the ratio (Table S7, entries 3–5). According to the above results,
the multicomponent reaction was preferred to carried out using
10 mol% of PANPAÀ2F in water at 80 °C (Table S5, entry 4).
With the optimized reaction conditions in hand, the generality
and scope of this method were then explored and the results are
summarized in Scheme 3. It can be seen that the aromatic aldehy-
des bearing electron-withdrawing as well as electron-donating
groups were converted smoothly to the corresponding 2-amino-
4H-chromenes in good to excellent yields. Although the position
of substituted groups on benzene ring did not significantly affect
the yield of product, the p-anisaldehyde afforded a slightly lower
yield compared to others. In addition, the heteroaromatic aldehy-
des such as furfural and thiophene-2-carbaldehyde also gave
desired products in high yields of 85% and 89%, respectively.
Encouraged by the above results, 1-naphthol was also employed
in the catalytic system as an enolizable compound with fused aro-
matic rings. It was observed that the trend of reactivities of differ-
ent aldehydes were similar to those of in the case of resorcinol.
Based on the efficiency of fiber catalyst PANPAÀ2F in the Knoeve-
nagel reaction, we decided to further explore the potential applica-
tion of our catalytic system in one-pot three-component synthesis
of 2-amino-4H-chromenes. These 2-amino-4H-chromene deriva-
tives are the important class of oxygen-containing heterocyclic
compounds with unique biological and pharmacological activities
such as antimicrobial, antifungal, estrogenic and anti-bacterial
properties [48]. In view of the great importance of such chromene