Single-step synthesis of 4-phenyl and 3,4-dihydro-4-phenyl coumarins using a recyclable Preyssler heteropolyacid catalyst under solvent-free reaction conditions

Article abstract of DOI:10.1007/s11164-015-2016-3

4-Phenyl and 3,4-dihydro-4-phenylcoumarins were prepared by direct esterification of phenols with phenylpropiolic and cinnamic acids, respectively, using a compound with Preyssler structure (H₁₄P₅NaW₃₀O₁₁₀) (PA)

Full text of DOI:10.1007/s11164-015-2016-3

Res Chem Intermed
DOI 10.1007/s11164-015-2016-3
Single-step synthesis of 4-phenyl and 3,4-dihydro-4-
phenyl coumarins using a recyclable Preyssler
heteropolyacid catalyst under solvent-free reaction
conditions
1
Angelica M. Escobar Diego M. Ruiz2
•
•
´
Juan C. Autino2 Gustavo P. Romanelli1,2
•
Received: 8 February 2015 / Accepted: 13 March 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract 4-Phenyl and 3,4-dihydro-4-phenylcoumarins were prepared by direct es-
terification of phenols with phenylpropiolic and cinnamic acids, respectively, using a
compound with Preyssler structure (H14P5NaW30O110) (PA) as heterogeneous catalyst
under solvent-free reaction conditions, at 130 °C, in a short reaction time (2 h). Under
these conditions, very good yields (11 examples: 61 %–90 %), free of secondary
products, were obtained. The catalyst is recyclable, nontoxic, neither air nor moisture
sensitive, and easy to handle. The described methodology is a clean and useful alter-
native to synthesize oxygenated heterocycles based on a coumarin skeleton.
Graphical abstract
OH
O
O
O
O
H14P5NaW30O110
CO2H
H14P5NaW30O110
CO2H
R
R
R
R1
R1
R1
130 ºC, solvent-free
R1
130 ºC, solvent-free
Keywords 4-Phenylcoumarins Á 4-Phenyl-3 Á 4-Dihydrocoumarins Á Preyssler
catalyst Á Recyclable catalyst Á Solvent-free reaction conditions
&
Gustavo P. Romanelli
gpr@quimica.unlp.edu.ar
1
´
Centro de Investigacion y Desarrollo en Ciencias Aplicadas ‘‘Dr. J. J. Ronco’’ (CINDECA),
Departamento de Quımica, Facultad de Ciencias Exactas, UNLP-CCT La Plata, CONICET,
´
1900 La Plata, Argentina
2
´
CISaV, Catedra de Quımica Organica, Facultad de Ciencias Agrarias y Forestales, UNLP,
Calles 60 y 119, B1904AAN La Plata, Argentina
´
´
123

A. M. Escobar et al.
Introduction
Heterocyclic compounds bearing coumarins are an important family of substances
that play a key role in organic synthesis, since they are present in a variety of
naturally occurring compounds. Particularly, both natural and synthetic molecules
containing coumarin moiety have interesting pharmacological and biological
properties [1].
Specifically, coumarins containing a 4-phenyl group have attracted wide
attention due to their interesting and unique properties such as antimalarial [2],
anticancer [3], anti-inflammatory [4], and fungicide activity [5]. Besides, some
4-phenylcoumarins also show antiviral activity, for example, mesuol inhibits HIV
replication in cells [6] and calocoumarin A acts on the Epstein-Barr virus that
causes mononucleosis [7] (Fig. 1a, b).
Furthermore, 3,4-dihydrobenzopyran-2-ones or dihydrocoumarins are well-
known as food flavoring [8], are used in perfumery industries [9] and as fragrance
in cosmetics [10]. 4-Phenyl-3,4-dihydrocoumarins are natural or synthetic com-
pounds that exhibit some interesting activities such as pesticides [11], antivirals
[12], antihypertensives [13], aldose reductase inhibitors [14] and antiherpetic agents
[15]. For instance, isorecedensolide and recedensolide (Fig. 1c) showed activity
against human cervical epitheloid carcinoma [16].
OH
OH
HO
O
O
O
O
O
(a) Mesuol
(b) Calocoumarin
O
O
HO
O
O
(c) Recedensolide
Fig. 1 Bioactive coumarins and dihydrocoumarins
123

Single-step synthesis of…
Among the traditional methods for the synthesis of 4-phenylcoumarins are the
Pechmann reaction for the condensation of phenols with benzoylacetic acid using
acid catalysts such as HCl, P2O5, BF3 ZnCl2, and heteropolyacids (HPA) [17–19];
the Perkin condensation between o-hydroxybenzophenones and Ac2O using AcONa
as catalyst [17]; the Wittig reaction of o-hydroxybenzophenones using ethoxycar-
bonyl triphenylphosphorane in benzene [17]; the Houben-Hoesch reaction of
benzoylacetonitriles with phenol using ZnCl2/HCl as catalyst, and the arylation of
coumarins [17]. Particularly, the Pondorff reaction involves the reaction of
phenylpropiolic acid with substituted phenol using an acid catalyst such as TFA
[20], P2O5/H3PO4 [21], montmorillonite K-10 [22] and HPA [23].
The methods for the synthesis of 4-phenyl-3,4-dihydrocoumarins include the
catalytic hydrogenation of coumarins [24–26], the Pondorff reaction for the
condensation of phenols with a, b-unsaturated acids in the presence of an acid
catalyst (for example, H2SO4 [17], P2O5/H3PO4H3 [27], TFA [28], BF3 [29],
zeolites [30], and montmorillonite K-10 using microwave irradiation [22]),
arylacrylate lactonization [20, 31–33], Houben-Hoesch condensation of phenols
with a,b-unsaturated nitriles in the presence of ZnCl2 [17] or AlCl3/HCl [34],
consecutive Friedel–Crafts alkylation-acylation [35], and via Fischer carbenes [36].
On the other hand, the use of heterogeneous catalysts has been widely studied
because they are easy to remove from the reaction media by simple filtration after
completion of the reaction and in general, they are reusable without appreciable loss
of their catalytic activity [37, 38].
Heteropolyacids (HPA) are well-defined molecular arrangements with remark-
able and useful applications. The main property is their reusability and the
possibility of generating heterogeneous catalysts [39]. Among the various possible
HPA structures, the Keggin-type primary structure deserves to be mentioned due to
its widely reported applications [40, 41]. As part of a research project to develop
environmentally friendly organic reactions, we used HPA with Preyssler structure,
in bulk or silica-supported, as a green and recyclable catalyst, in the protection/
deprotection of functional groups [42], and in the synthesis of diverse organic
compounds such as esters of cinnamic acids from the reaction between phenols and
imidoalcohols [43], N-sulfonyl-1,2,3,4-tetrahydroisoquinolines [44], flavones [45],
3H-1,5-benzodiazepines [46], and fluorinated hexahydropyrimidines [47].
In the present work we describe the use of a Preyssler heteropolyacid
(H14P5NaW30O110) as a recyclable acid catalyst in the synthesis of coumarin
O
O
CO2H
OH
Preyssler catalyst, 0.5 %
130 ºC, solvent-free
R
+
R1
R
R1
Scheme 1 Synthesis of 4-phenylcoumarins
123

A. M. Escobar et al.
O
O
OH
CO2H
Preyssler catalyst, 0.5 %
130 ºC, solvent-free
R
+
R
R1
R1
Scheme 2 Synthesis of 4-phenyl-3,4-dihydrocoumarins
derivatives. Scheme 1 shows the synthesis of 4-phenylcoumarins and Scheme 2 the
synthesis of 4-phenyl-3,4-dihydro-4-phenylcoumarins.
Experimental
General
Chemicals were purchased from Aldrich, Fluka and Merck, and were freshly used
after purification by standard procedures (distillation and recrystallization). All the
reactions were monitored by TLC on precoated silica gel plates (254 mm). Flash
column chromatography was performed with 230–400 mesh silica gel. All the yields
were calculated from crystallized products. All the products were identified by
comparison of physical data (mp, TLC and NMR) with those reported or with those
of authentic samples prepared by the respective conventional methods using sulfuric
acid as catalyst.
Instrumentation
Melting points of the compounds were determined in sealed capillary tubes and are
uncorrected. The 1H-NMR and 13C-NMR spectra were obtained on a Bruker
instrument 400 MHz model as CDCl3 solutions, and the chemical shifts were
expressed in d units with Me4Si (TMS) as the internal standard.
Catalyst preparation
For the preparation of the Preyssler salt K12,5Na1,5(NaP5W30O110)Á15H2O (PS), a
procedure described by Creaser and coworkers [48] was used with minor
modifications. In a typical experiment 16.3 g (0.05 mol) Na2WO4.2H2O was
dissolved in 15 ml water and mixed at 65 °C for 45 min. The solution was cooled to
20 °C and then, 14 ml concentrated phosphoric acid (85 %) was added. The
resulting yellow solution was refluxed for 24 h. The color turned to dark green at the
end of reaction. The solution was brought to room temperature, diluted with 20 ml
water and then, 10 g potassium chloride was added with stirring. The mixture was
stirred for 60 min and then heated up to dryness, and a greenish solid was obtained.
This raw product was dissolved in 35 ml warm water and upon cooling to room
123

Single-step synthesis of…
temperature white crystals formed, which were collected and recrystallized from
boiling water (yield, 21 %). The heteropolyanion was converted to its correspond-
ing acid H14(NaP5W30O110) (PA) by passing an aqueous solution of PS through a
Dowex-50 W-98 ion exchange column.
Catalytic test: 4-phenylcoumarins
The catalyst was dried overnight prior to use. A mixture of the corresponding
phenol (1 mmol), phenylpropiolic acid (1 mmol) and PA catalyst (0.5 mmol %)
was placed in an open glass tube (20 ml) and stirred at 120 °C for the indicated
time. When the reaction time was over, the reaction mixture was extracted with hot
toluene (2 9 3 ml). The solution was concentrated in vacuum, and the crude
product was recrystallized from methanol or ethanol. Alternatively, the catalyst was
extracted with water (3 9 5 ml) and the crude product was recrystallized from
methanol or ethanol.
3,4-Dihydro-4-phenylcoumarins
The catalyst was dried overnight prior to use. A mixture of the corresponding
phenol (1 mmol), cinnamic acid (1 mmol) and PA catalyst (0.5 mmol %) was
placed in an open glass tube (20 ml) and stirred at 130 °C for the indicated time.
When the reaction time was over, the reaction mixture was extracted with hot
toluene (2 9 3 ml). The extract was washed with H2O (2 ml) and then dried with
anhydrous sodium sulfate and filtered. Evaporation of the solvent under reduced
pressure and recrystallization from methanol or ethanol gave the pure products.
Catalyst reuse
Stability tests of the bulk PA catalysts were performed running four consecutive
experiments, under the same reaction conditions. After each test, the catalyst was
separated from the reaction mixture by filtration, washed with toluene (2 9 2 ml),
dried under vacuum, and then reused.
Characterization data of compounds
Al spectra correspond to the products achieved at the best reaction conditions
(time = 2 h, temperature = 90 °C, catalyst = 0.5 %).
4-Phenylcoumarin (entry 1): mp: 102–104 °C (methanol) (lit. mp: 105 °C [23]);
1H NMR (400 MHz, CDCl3) d 6.41 (s, 1H), 7.22 (dd, 2H, J = 2.5, 8 Hz), 7.30 (m,
5H), 7.50 (dd, 2H, J = 2.5, 8 Hz). 13C NMR (100 MHz, CDCl3) d 106.1, 121.4,
125.1, 126.1, 126.3, 126.5, 127.5, 127.8, 128.1, 135.0, 148.1, 159.2, 162.2.
7-Hydroxy-4-phenylcoumarin (entry 2): mp: 238–240 °C (methanol) (lit. mp:
1
240 °C [23]); H NMR (400 MHz, CDCl3) d 6.43 (s, 1H), 6.71 (dd, 2H, J = 2.5,
8 Hz), 7.46 (d, 1H, J = 8 Hz), 7.49–7.62 (m, 5H), 7.89 (s, 1H). 13C NMR
(100 MHz, CDCl3) d 105.0, 105.7, 112.4, 120.3, 126.0, 127.4, 127.8, 128.1, 135.2,
151.3, 158.6, 158.9, 162.0.
123

A. M. Escobar et al.
7-Methoxy-4-phenylcoumarin (entry 3): mp: 107–108 °C (methanol) (lit mp:
106–108 °C [49]); 1H NMR (400 MHz, CDCl3) d 7.54-7.47 (m, 3H), 7.48 - 7.42
(m, 2H), 7.39 (d, J = 8.9 Hz, 1H), 6.87 (d, J = 2.5 Hz, 1H), 6.77 (dd, J = 8.9,
2.5 Hz, 1H), 6.21 (s, 1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) d163.8,
161.2, 156.0, 155.7, 135.6, 129.5, 128.9, 128.4, 128.2, 112.5,112.3, 111.9, 101.4,
54.9.
6-Methyl-4-phenylcoumarin (entry 4): mp: 135–137 (methanol) (lit. mp:
1
134.7–135.1 °C [50]) H NMR (300 MHz, CDCl3) d 2.35 (s, 3H, CH3), 6.34 (s,
1H, vinyl), 7.27 (s,1H, aryl), 7.32 (d, J) 8.1 Hz, 1H, aryl), 7.38 (dd, J) 2.1, 8.1 Hz,
1H, aryl), 7.45 (m, 2H, aryl), 7.55 (m, 3H, aryl); 13C NMR (100 MHz, CDCl3) d
20.9, 115.1, 117.0, 118.6, 126.8,128.4, 128.8, 129.5, 132.8, 133.8, 135.34, 152.3,
155.5,160.9.
6-Methoxy-4-phenylcoumarin (entry 5): mp 147–149 °C (methanol) (lit. mp:
1
148–149 °C [49]) H NMR (400 MHz, CDCl3) d 7.57 - 7.50 (m, 3H), 7.46 (dd,
J = 6.6, 2.9 Hz, 2H), 7.34 (d, J = 9.0 Hz, 1H), 7.13 (dd, J= 9.0, 2.9 Hz, 1H), 6.93
(d, J = 2.9 Hz, 1H), 6.38 (s, 1H), 3.74 (s, 3H); 13C NMR CDCl3) d 161.1, 156.0,
155.5, 148.7, 135.4, 129.7, 129.1, 128.5, 119.6, 119.1, 118.4, 115.8, 110.1, 55.9.
4-(4-Methoxyphenyl)-coumarin (entry 6): mp: 128–129 °C (methanol) (lit mp:
129–130 °C [51]) 1H NMR (400 MHz, CDCl3) d 3.91 (s, 3H), 6.35 (s, 1H), 7.05 (d
J 8.8 Hz, 2H), 7.24 (dd, J 8.5, 7.2, 1,2 Hz, 1H), 7.39–7.42 (d, J 8.7 Hz, 2 H), 7.54
(dd, J 7.8, 1.5 Hz), 1H), 7.57 (d, J 7.8 Hz, 1H) Carbon: 55.5, 114.1, 114.5,
117.5,119.2, 124.0, 127.0, 127.7,129.9, 131.8, 154.2, 155.3, 159.9
4-Phenyl-3,4-dihydrocoumarin (entry 7): mp: 78–79 °C (methanol) (lit. mp:
80–82 °C [23]); 1H NMR (400 MHz, CDCl3) d 3.13 (dd, 2H, J = 6, 16 Hz), 4.37 (t,
1H, J = 6 Hz), 6.99 (d, 1H, J = 8 Hz), 7.01 (d, 1H, J = 8 Hz), 7.08–7.14 (m, 1H),
7.26–7.41 (m, 5H). 13C NMR (100 MHz, CDCl3) d 37.1, 40.7, 125.3, 125.5, 125.8,
126.8, 127.5, 129.8, 130.4, 143.3, 148.6, 167.7.
6-Methyl-4-phenyl-3,4-dihydrocoumarin (entry 8): mp: 80–81 °C (methanol) (lit.
1
mp: 80–83 °C [52]); H NMR (400 MHz, CDCl3) d 2.27 (s, 3H), 2.98–3.10 (m,
2H), 4.32 (t, 1H, J = 6.8 Hz), 6.82 (s, 1H), 7.05 (d, 1H, J = 8 Hz), 7.15 (d, 1 H,
J = 8 Hz), 7.28 (d, 2H, J = 5.1 Hz), 7.34 (m, 3H). 13C NMR (100 MHz, CDCl3) d
21.2, 36.3, 40.2, 125.4, 125.7, 125.8, 127.0, 128.1, 129.9, 135.5, 143.3, 148.5, 17.7
7-Methyl-4-phenyl-3,4-dihydrocoumarin (entry 9): mp 124–125 °C (methanol)
(lit. mp: 124 °C [52]); 1H NMR (400 MHz, CDCl3) d 2.38 (s, 3H), d 3.13–2.99 (m,
2H), d 4.35(t, 1H, J = 6.80 Hz), d 6.92(q, 2H, J = 8 Hz), d 6.98 (s, 1H), d 7.18 (d,
2H, J = 7.6 Hz), d 7.35(m, 3H). 13C NMR (100 MHz, CDCl3) d 21.5, 37.2, 40.8,
125.4, 125.7, 125.8, 127.5, 129.8, 131.4, 135.5 143.3, 148.6, 167.7.
8-Methyl-4-phenyl-3,4-dihydrocoumarin (entry 10): mp 105–107 (methanol) (lit.
mp: 106–108 °C [52]); 1H NMR (400 MHz, CDCl3) d 2.36 (s,3H), d 3.10–2.99 (m,
2H), d 4.32 (t, 1H, J = 6.8 Hz), d 6.81 (d, 1H, J = 7.6 Hz), d 6.98 (t, 1H,
J = 7.6 Hz), d 7.15 (d, 3H, J = 7.2 Hz), d 7.33–7.26 (m, 3H).13C NMR
(100 MHz, CDCl3) d 21.4, 37.3, 40.9, 125.3, 125.7, 125.8, 129.8, 131.4, 135.5,
135.7, 143.3, 148.6, 167.7.
4(4-Methylphenyl-3,4-dihydrocoumarin (entry 11): mp 103–104 °C (methanol)
mp: 103–104 °C (lit. no data); 1H-RMN (400 MHz, CDCl3), d (ppm): 1,25 (3H, s);
3.10–3.16 (2H, dd, J = 6 Hz; 16 Hz); 4.37 (1H, t, J = 6 Hz); 6.99 (1H, d,
123

Single-step synthesis of…
J = 8 Hz); 7.01 (1H, d, J = 8 Hz); 7.08–7.14 (1H, m, J = 8 Hz); 7.15–7.21 (2H,
m, J = 8 Hz); 7.27–7.39 (4H, m).13C-RMN (100 MHz, CDCl3): 19.8; 37.2; 40.7;
125.0; 125.5; 125.8; 126.7; 127.5; 128.3; 129.7; 133.6; 140.2; 148.2; 167.5.
Green metrics
In order to quantify how much ‘greener’ the presented methodology is, various
green metric parameters were calculated for each reaction performed, namely,
quantitative factors such as atom economy (AE), atomic efficiency factor (E),
process mass intensity (PMI) and semiquantitative EcoScale.
Results and discussion
Optimal reaction conditions were examined employing phenol and phenylpropiolic
acid as test reaction substrate under solvent-free reaction conditions at 130 °C for
2 h. Without the presence of catalyst, no reaction was observed. First, the influence
of the reaction temperature on 4-phenylcoumarin synthesis was tested using PA.
The tested experimental reaction conditions were: phenol (1 mmol), phenylpropi-
olic acid (1 mmol) catalyst (0.005 mmol), and 2 h of reaction time under solvent-
free reaction conditions. The results are listed in Table 1. In order to obtain the
optimal temperature, four temperatures (90, 110, 130 and 150 °C, Table 1) were
tested. No reaction was observed at 90 °C (entry 1, Table 1).
A temperature increase leads to a higher 4-phenylcoumarin yield. For example,
the yield of 4-phenylcoumarin for a reaction time of 2 h at 110 °C was only 54 %
(entry 2, Table 1), whereas at 130 °C the yield was 90 % (entry 3, Table 1). Finally,
at 150 °C the reaction yield was lower, 62 %, (entry 4, Table 1) due to the several
unidentified side products that were detected by thin layer chromatography.
For this reason, 130 °C was employed as the ideal temperature to continue with
the next experiment for the analysis of the other reaction variables. Table 2 shows
the results for 4-phenylcoumarin synthesis at different reaction times using PA
catalyst at 130 °C. The experimental reaction conditions were: phenol (1 mmol),
phenylpropiolic acid (1 mmol), catalyst (0.005 mmol), at 130 °C under solvent-free
Table 1 Effect of temperature on 4-phenylcoumarin yields (%)
Entry
Temperature (8C)
Yielda (%)
1
2
3
4
90
110
130
150
–
54
90
62
Reaction conditions: phenol, 1 mmol; 3-phenylpropiolic acid, 1 mmol; catalyst, 0.5 % mmol; 2 h; stir-
ring; under solvent-free reaction conditions
a
Isolated yields
123

A. M. Escobar et al.
Yielda (%)
Table 2 Effect of reaction time on 4-phenylcoumarin yields (%)
Entry
Reaction time (h)
1
2
3
4
0.5
1
29
54
90
88
2
3
Reaction conditions: phenol, 1 mmol; 3-phenylpropiolic acid, 1 mmol; catalyst, 0.5 % mmol; 130 °C;
stirring; under solvent-free reaction conditions
a
Isolated yields
Table 3 Effect of the amount of catalyst on 4-phenylcoumarin yields (%)
Entry
Amount of catalyst (%)
Yielda (%)
1
2
3
4
0.1
0.5
1
39
90
90
91
2
Reaction conditions: phenol, 1 mmol; 3-phenylpropiolic acid, 1 mmol; 130 °C; 2 h; stirring; solvent-free
reaction conditions
a
Isolated yields
Table 4 Effect of catalyst reuse on 4-phenylcoumarin yields (%)
Entry
Catalytic cycle
Yielda (%)
1
2
3
4
1
2
3
4
90
88
84
80
Reaction conditions: phenol, 1 mmol; 3-phenylpropiolic acid, 1 mmol; catalyst, 0.5 % mmol; 2 h;
130 °C; stirring; in solvent-free reaction conditions
a
Isolated yields
reaction conditions. It can be observed that the yields of 4-phenylcoumarin
increased with the reaction time up to 2 h and then remained practically constant
(ca. 90 %, Table 2, entries 3 and 4).
Table 3 shows the effect of the amount of catalyst (PA) on the yield of
4-phenylcoumarin in the reaction. The experimental conditions were: phenol
(1 mmol), phenylpropiolic acid (1 mmol), with a reaction time of 2 h at 130 °C
under solvent-free reaction conditions, with a variable amount of PA catalyst (0.1,
0.5, 1, and 2 %). It can be seen that the yields increased from 39 to 90 % when the
amount of PA increased from 0.1 to 0.5 % (Table 3, entries 1 and 2), and no
relevant changes in the reaction yield were observed with further increase in the
123

Single-step synthesis of…
Table 5 Synthesis of 4-phenylcoumarins and 4-phenyl-3,4-dihydrocoumarins
Entry
1
Product
Yield (%)
90
AE (%)
92.5
E
PMI
43.4
EcoScale
86
42.1
O
O
2
3
4
88
84
83
92.9
93.3
92.9
40.2
39.8
43.0
41.5
40.5
44.4
85
H
O
O
O
83
H
3CO
O
O
83.5
O
O
H
3C
123

A. M. Escobar et al.
Table 5 continued
Entry
5
Product
Yield (%)
80
AE (%)
93.3
E
PMI
43.1
EcoScale
81
41.7
O
O
H
3CO
6
78
93.3
42.8
44.3
80
O
O
H
OC
3
7
61
92.6
76.4
78.3
56.5
O
O
8
77
93.0
56.9
58.5
64.5
O
O
123

Single-step synthesis of…
Table 5 continued
Entry
9
Product
Yield (%)
73
AE (%)
93.0
E
PMI
61.7
EcoScale
62.5
60.1
O
O
10
71
93.0
61.7
63.4
61.5
O
O
11
66
93.0
66.4
68.3
59
O
O
Reaction conditions: phenols, 1 mmol; 3-phenylpropiolic acid, or cinnamic acid, 1 mmol; catalyst,
0.5 % mmol; 2 h; 130 °C; stirring; in solvent-free conditions
a
Isolated yields
amount of PA (2 %), (91 %, Table 3, entry 4). Thus, 0.5 % of PA is a suitable
amount for performing this reaction.
The reuse of the catalyst was investigated in the consecutive reaction of phenol
and phenylpropiolic acid in solvent-free reaction conditions. At the end of each run
the catalyst was removed, washed with toluene, dried in vacuum at 25 8C and
reused. The results are summarized in Table 4. The catalyst was reused three runs
and no appreciable loss of its catalytic activity was observed. The performance of
the reactions under the same conditions using PA as catalyst showed 90, 88 and
123

A. M. Escobar et al.
Table 6 Green metric comparison of classic synthesis methods with the techniques described in this
work
Method
Yield (%)
AE (%)
E factor
PMI
99
EcoScale
Pechmann (coumarins) [17]
This paper (coumarins)
39
90
70
61
79.4
92.5
92.6
92.6
98.5
42.1
28
43.4
86
Pondorff (dihydrocoumarins) [30]
This paper (dihydrocoumarins)
109.1
76.4
111.1
78.3
42
56.5
Scheme 3 Proposed mechanism for 3,4-dihydro-4-phenylcoumarin synthesis
84 % of 4-phenylcoumarin yield, respectively. In the four cycles, the reaction yield
was 80 % in 3 h.
Using the optimized conditions: phenol (1 mmol), phenylpropiolic acid (1 m-
mol), PA catalyst (0.5 % mmol) at 130 °C, 2 h of reaction time, and solvent-free
conditions (Scheme 1), six substituted 4-phenylcoumarins were prepared (Table 5).
In all the experiments, the desired products were obtained with high selectivity.
Similarly, we achieved the sustainable, solvent-free preparation of seven
substituted 4-phenyl-3,4-dihydrocoumarins from phenols and a, b-unsaturated
carboxylic acids (Scheme 2) using PA as catalyst in the optimized conditions. For
example, 6-methyl-4-phenyl-3,4-dihydrocoumarin was obtained in a yield of 77 %
and free of secondary products from the reaction of a stoichiometric amount of
4-methylphenol and cinnamic acid, 0.5 % of PA (Table 5, entry 8).
123

Single-step synthesis of…
In order to quantify how much ‘greener’ the methodology is, the atom economy,
atomic efficiency factor, process mass intensity, and EcoScale were calculated for
each reaction product and the results are also presented in Table 5. The resulting
parameters were also compared with classic methods for the synthesis of coumarins
and dihydrocoumarins [17, 30]. The results (listed in Table 6) indicate an
improvement in the synthesis of coumarins from a green chemistry viewpoint,
with better yield, atom economy, environmental factor, process mass intensity and
EcoScale factors. Similarly, dihydrocoumarin preparation results in a greener
procedure in view of the E-factor, PMI and EcoScale parameters.
Scheme 3 displays a plausible reaction mechanism for 3,4-dihydrophenyl-
coumarin formation using phenol and cinnamic acid as substrate catalyzed by the
Preyssler heteropolyacid (PA).
Conclusions
The procedure described for the synthesis of 4-phenylcoumarins and 3,4-dihydro-4-
phenylcoumarins (dihydrocoumarins), using a heteropolyacid with Preyssler
primary structure in bulk form, is a clean and useful alternative. The advantages
of this methodology are operative simplicity, use of a reusable and noncorrosive
solid acid catalyst, soft reaction conditions, low reaction times, and good yields. In
these conditions, proved to be greener by various green metric parameters, very
good yields (11 examples: 61–90 %) of 4-phenylcoumarin derivatives free of
secondary products were obtained.
Acknowledgments We thank Universidad Nacional de La Plata, CONICET, ANPCyT and UPTC for
financial support. GR is a member of CONICET.
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