ꢀ
M. Perez et al. / C. R. Chimie xxx (2016) 1e5
3
2-Furylchromone (8). Mp: 134e135 ꢀC (methanol) (lit.
reaction conditions were: 1-(2-hydroxyphenyl)-3-phenyl-
1,3-propanodione (0.5 mmol), 200 mg of KHSO4, and the
mixture reaction was stirred for 120 min. No reaction was
observed at 25, 60 and 80 ꢀC. A further temperature in-
crease leads to a higher flavone yield. For example, the yield
of flavone for a reaction time of 120 min at 100 ꢀC was 80%.
At 120 ꢀC, at the same reaction time, yield was 98%. Finally,
at 140 ꢀC the reaction yields were considerably lower (67%),
due to the several unidentified side products that were
detected by TLC. For this reason, 120 ꢀC was employed as
the ideal temperature to continue with the analysis of other
reaction variables.
Results for the reaction time for flavone synthesis under
the same reaction conditions (flavone, 0.5 mmol; catalyst,
400 mg; temperature, 120 ꢀC, and reaction time, 120 min)
shows that yields of flavone increased when the reaction
time increased to approx. 120 min and then remained at a
constant level.
The effects of the amount of catalyst (KHSO4)
on the yield of flavone under the experimental
conditions were tested from 1-(2-hydroxyphenyl)-3-
phenyl-1,3-propanodione, 0.5 mmol; 120 ꢀC, 120 min,
using a variable amount of the KHSO4 catalyst (50, 100,
150, 200 and 250 mg). The yields increased from 88% to
98% when the amount of KHSO4 increased from 150 to
200 mg. No relevant changes of reaction yields were
observed with further increase in the amount of KHSO4.
Thus, 200 mg of KHSO4 results in the suitable amount for
this reaction.
mp: 135 C) [32]; 1H NMR (CDCl3, 250 MHz),
d: 6.61e6.63
ꢀ
(1H, m), 6.75 (1H, s), 7.14 (1H, d, J ¼ 3.3 Hz), 7.41 (1H, m),
7.50 (1H, d, J ¼ 8.2 Hz), 7.65e7.72 (2H, m), 8.22 (1H, dd,
J ¼ 7.4, 1.2 Hz). 13C NMR (CDCl3, 62.5 MHz);
d: 105.2, 112.1,
112.6, 117.6, 124.0, 124.8, 125.4, 133.3, 145.5, 146.1, 154.9,
155.5, 177.3.
2-(2-Naphthyl)chromone (9). Mp: 162e163 ꢀC (meth-
anol) (lit. mp: 164e165 ꢀC) [33]; 1H NMR (400 MHz, CDCl3),
d
: 6.96 (s, 1H), 7.43 (ddd, 1H, J ¼ 8.0, 6.5, 1.5 Hz), 7.55e7.62
(m, 2H), 7.62 (d, 1H, J ¼ 8.0 Hz), 7.71 (ddd, 1H, J ¼ 8.0, 6.5,
1.5 Hz), 7.85e8.02 (m, 4H), 8.24 (dd, 1H, J ¼ 7.9, 1.4 Hz), 8.47
(s, 1H). 13C NMR (100 MHz, CDCl3),
d: 108.0, 118.3, 122.6,
124.2, 125.5, 125.9, 127.1, 127.2, 128.0, 128.2, 129.0, 129.1,
130.1, 133.0, 134.0, 134.8, 156.5, 163.5, 178.6.
2-(1-Naphthyl)chromone (10). Mp: 142e143 ꢀC (meth-
anol)(lit. mp:138e139 ꢀC)[33];1HNMR(400MHz, CDCl3),
d:
6.69 (s, 1H), 7.42 (dt, 1H, J ¼ 7.8, 1.3 Hz), 7.49e7.59 (m, 4H),
7.71 (dt, 1H, J ¼ 7.8, 1.8 Hz), 7.77 (dd, 1H, J ¼ 7.6, 1.2 Hz),
7.91e7.94 (m, 1H), 8.03 (d, 1H, J ¼ 8.1 Hz), 8.10e8.13 (m, 1H),
8.32 (dd, 1H, J ¼ 7.8, 1.5 Hz). 13C NMR (100 MHz, CDCl3),
d:
113.0, 118.2, 123.9, 125.0, 125.3, 125.4, 125.7, 126.5, 127.4,
127.5,128.7,130.3,130.6,131.5,133.7,133.8,156.6,165.2,177.9.
ꢀ
7-Chloro-2-(2-naphthyl)chromone (11). Mp: 219e220 C
(methanol) (lit. mp: 219e220 ꢀC) [34]; 1H NMR (250 MHz,
CDCl3),
d
: 6.96 (s, 1H), 7.42 (dd, 1H, J ¼ 8.6, 2.0 Hz),
7.57e7.65 (m, 2H), 7.68 (d, 1H, J ¼ 2.0 Hz), 7.89e8.01 (m,
4H), 8.21 (d, 1H, J ¼ 8.6 Hz), 8.47 (s, 1H) 13C NMR (62.5 MHz,
CDCl3), d: 108.4, 118.5, 122.7, 122.9, 126.4, 127.2, 127.3, 127.4,
128.1, 128.5, 128.9, 129.3, 129.4, 133.6, 135.1, 140.1, 156.7,
163.7, 177.6.
The scale-up in chemical engineering is the migration of
a process from the lab scale to the pilot plant scale or
commercial scale. We performed the reaction at different
scales from 1 mmol to 0.1 mol. This topic is very important
in solvent-free reactions because it is difficult to achieve
uniformity between the substrates and the catalyst in the
system. However no significant changes in the reaction
yields were observed.
The reusability of the catalysts was investigated in the
sequential reaction of cyclodehydration of 1-(2-
hydroxyphenyl)-3-phenyl-1,3-propanodione. At the end
of each run the catalyst was removed, washed with toluene,
dried in the vacuum at 40 ꢀC and reused. The results
showed that the reuse of the catalyst in four consecutive
runs results in no appreciable loss of its catalytic activity
(98%, 96%, 96%, and 95% of flavone yields, respectively).
Under the optimized conditions: substituted 1-(2-
ꢀ
7-Chloro-2-(1-naphthyl)chromone (12). Mp: 198e199 C
1
ꢀ
(methanol) (lit. mp: 198e199 C) [35]; H NMR (400 MHz,
CDCl3),
d
: 6.72 (s, 1H), 7.48 (dd, 1H, J ¼ 1.9, 8.5 Hz),
7.61e7.66 (m, 4H), 7.81 (dd, 1H, J ¼ 7.2, 1.1 Hz), 7.99e8.01
(m, 1H), 8.08 (d, 1H, J ¼ 8.2 Hz), 8.15e8.17 (m, 1H), 8.29 (d,
1H, J ¼ 8.6 Hz). 13C NMR (100 MHz, CDCl3),
d: 113.6, 118.7,
122.8, 124.9, 125.4, 126.5, 127.0, 127.4, 127.9, 128.3, 129.1,
130.4, 130.6, 131.9, 134.1, 140.2, 157.1, 165.9, 177.7.
2. Results and discussion
In this work we report on the use of a solvent-free sys-
tem for the preparation of 2-arylchromones in the presence
of KHSO4 as a cheap and reusable catalyst. The flavone and
chromone synthesis involves the cyclodehydration of 1-(2-
hydroxyphenyl)-3-aryl-1,3-propanodiones under solvent-
free conditions (Scheme 1).
hydroxyphenyl)-3-aryl-1,3-propanodione,
0.5
mmol;
KHSO4, 200 mg; 120 ꢀC; and 120e150 min, twelve flavones
and chromones were prepared. Results are given in Table 1.
In all the cases, the desired products were obtained with
high selectivity, almost free of secondary products. The
unchanged starting materials were recovered nearly
quantitatively. No relevant stereoelectronic effects on the
yields due to the substituent were observed.
Initially,
a
noncatalytic experiment using 1-(2-
hydroxyphenyl)-3-phenyl-1,3-propanodione (120 mg,
0.5 mmol) was tested, and it was observed that, under the
experimental conditions (120 ꢀC,120 min and solvent-free),
only traces of flavone were detected, indicating that from a
practical point of view the reaction is not taking place in the
absence of a catalyst.
Then, the KHSO4 catalyst was tested with very
good results. First, the influence of the reaction tempera-
ture on 1-(2-hydroxyphenyl)-3-phenyl-1,3-propanodione
was analyzed using 200 mg of KHSO4. In order to
obtain the optimal temperature, five temperatures were
studied (25, 60, 80, 100, 120 and 140 ꢀC). The experimental
Finally, in order to quantify how much 'greener' the
methodology is, the Atom Economy (AE), Atomic effi-
ciency factor (E), Process Mass Intensity (PMI) and Eco-
Scale were calculated for each reaction product and the
results are presented in Table 1 for each compound. We
compared these values with the ones previously reported
in the literature, and it is important to note that this
ꢀ
Please cite this article in press as: M. Perez, et al., A very simple solvent-free method for the synthesis of 2-arylchromones using
KHSO4 as a recyclable catalyst, Comptes Rendus Chimie (2016), http://dx.doi.org/10.1016/j.crci.2016.02.014