Hydroarylation of cinnamic acid with phenols catalyzed by acidic ionic liquid [H-NMP]HSO4: computational assessment on substituent effect

Article abstract of DOI:10.1007/s11164-016-2471-5

Hydroarylation of cinnamic acid with different substituted phenols, in the presence of acidic ionic liquid, N-methyl-2-pyrrolidonum hydrosulfate ([H-NMP]HSO₄) gave the corresponding dihydrocoumarins in high yields and excellent selectivity. Amo

Full text of DOI:10.1007/s11164-016-2471-5

Res Chem Intermed
DOI 10.1007/s11164-016-2471-5
Hydroarylation of cinnamic acid with phenols catalyzed
by acidic ionic liquid [H-NMP]HSO4: computational
assessment on substituent effect
Vahideh Zadsirjan1 Majid M. Heravi1
•
•
Mahmoud Tajbakhsh2 Hossein A. Oskooie1
Morteza Shiri1 Tayebeh Hosseinnejad1
•
•
•
Received: 26 November 2015 / Accepted: 1 February 2016
Ó Springer Science+Business Media Dordrecht 2016
Abstract Hydroarylation of cinnamic acid with different substituted phenols, in
the presence of acidic ionic liquid, N-methyl-2-pyrrolidonum hydrosulfate
([H-NMP]HSO4) gave the corresponding dihydrocoumarins in high yields and
excellent selectivity. Among these substituted phenols, while methyl phenol
afforded the corresponding dihydrocoumarin, nitrophenol under the same reaction
conditions diverted the course of reaction, affording 3-(4-nitrophenyl)-3-phenyl-
propanoic acids. We investigated this behavior from the energetic and electronic
points of view, using quantum chemistry computational methods. In this respect, the
electronic energy change values for the conversion reaction of substituted phenyl
cinnamate esters to dihydrocoumarin compounds have been obtained via density
functional theory calculations. We demonstrated that the conversion reaction in the
presence of CH3 substituent is more favorable energetically than NO2 substituent.
Moreover, we have concentrated on topological analysis of electron density on some
key bond and ring critical points and their associated bond paths to assess the
conversion of substituted phenyl cinnamate esters to dihydrocoumarins. Our cal-
culated results showed that para-methyl phenyl cinnamate has more of electronic
tendency to undergo the intramolecular cyclization step and, consequently, generate
the corresponding dihydrocoumarin.
Keywords Dihydrocoumarins Á 3-(4-Nitrophenyl)-3-phenylpropanoic acids Á Ionic
liquid Á Phenols Á Cinnamic acid Á DFT methods Á QTAIM analysis
&
Majid M. Heravi
mmh1331@yahoo.com
1
2
Department of Chemistry, Alzahra University, Vanak, Tehran, Iran
Department of Chemistry, Mazandaran University, Babolsar, Mazandaran, Iran
123

V. Zadsirjan et al.
Introduction
Coumarin derivatives as a molecule or scaffold exist extensively in plants. They
exhibit a wide scope of pharmacological activities [1, 2] such as anti-cancer, anti-
aging, anti-inflammatory and anti-oxidative [3]. For instance, tannin-containing
plant extracts contain the 4-aryldihydrocoumarin moiety and have traditionally been
used for the treatment of infection diseases for centuries in China [4–10]. The anti-
fungal and anti-TB potencies of several coumarin derivatives as a new class of
pharmacophore have also been studied [11–14]. They have also been widely
employed as additives in perfumes, cosmetics, pharmaceuticals, and food, as well as
optical brighteners, dispersed fluorescents, and laser dyes [15].
4-Aryl-3,4-dihydrocoumarins are natural products [16–18], which show some
significant biological activities such as aldose reductase inhibition [8], antiherpetics
[19], protein kinases [9]. They are also used as intermediates in the synthesis of
more complicated targets, showing biological activities. For instance 4-aryl-3,
4-dihydrocoumarins has been employed as starting materials for the synthesis of N-
diaryl (aryl) substituted amides, showing antiarrhythmic properties [20].
The most common strategy for the synthesis of dihydrocoumarins is acid-catalzed
hydroarylation of cinnamic acids with differently substituted phenols [21–23]. Other
methods include: the catalytic hydrogenation of coumarins [24, 25], Lewis acid
catalyzed reaction of activated phenols with acrylonitrile [26, 27], the Fischer carbene
complex reaction with ketene acetals [28], p-TSA catalyzed hydroarylation of
cinnamic acids with various phenols [29], AlCl3 catalyzed C–C coupling reaction
between hydroxyketene s,s-acetals and arenes [30], [4 ? 2] cycloaddition reaction of
o-quinone methides with silyl ketene acetals [31], bio-conversion of coumarins by
certain kind of microorganisms [32], microwave-promoted reaction of phenols and
cinnamoyl chloride in the presence of montmorillonite K-10 as heterogeneous catalyst
in solvent-free conditions [33], microwave-assisted reaction of phenols and cinnamic
acids mediated by silica supported Wells–Dawson heteropolyacid [34], p-TSA
mediated hydrolysis of aryl cinnamic esters [35], and trifluoroacetic acid-catalyzed
hydroarylation of cinnamic esters with tyroso [36]. There is also the preparation of
trifluoromethylated dihydrocoumarins, by tandem super acidic activation of 2-(tri-
fluoromethyl)acrylic acid with arenes that have been accomplished and reported [37].
Also, solvent-free synthesis of 4-aryl-3, 4-dihydrobenzopyran-2-ones through
[3 ? 3] cyclo-coupling of phenols with cinnamic acid mediated by molecular iodine
has been reported [38, 39].
These methods have their own merits and drawbacks such as the deficiency of
substrate generality and the use of a large excess of expensive chemicals such as
trifluoroacetic acid [23], and the general concerns regarding the transition metals-
catalyzed reactions [23, 40, 41].
In the few past decades, ionic liquids have attracted much attention and interest
in the context of green synthesis of organic compounds due to their adaptable phys-
ical and chemical properties [42]. Because of these properties, such as high thermal
and chemical stability, low vapor pressure, good solvating ability, ease of recovery,
reusability, and controlled miscibility, they are suitable for being used as an
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
alternative green reaction media [43–49]. Perhaps, one of the most important
features of ionic liquid is its dual role, both as solvent and catalyst [50–54]. These
unique properties are the result of being molten salts, liquefied below 100 °C, which
generally consist of a cation (such as imidazolium, pyrrolidinium, pyridinium,
tetraalkyl ammonium or tetraalkyl phosphonium) and or an anion (e.g., tetrafluo-
roborate, hexafluorophosphate, and bromide). In addition, after the first econom-
ically feasible industrial process employing ionic liquids by BASF (BASIL10
process) in 2003 [55, 56], the applicability of various ionic liquids for other
reactions have become well-known and widely accepted. Thus, it is worthwhile, to
examine inexpensive commercially available or readily accessible ionic liquids in
the synthesis of useful compounds as catalyst or/and solvent.
Since most compounds are soluble in ionic liquids, acidic ILs can be used in
¨
several reactions, both as catalyst and solvent. In this context, acidic Bronsted ionic
liquid, pyrrolidinium bisulfate [HNMP] HSO4, can be considered as a good
candidate, being examined in reactions leading to useful organic compounds [57–
59]. Noticeably, it can be prepared by a facile method, just upon treatment of
1-methyl-2-pyrrolidone with sulfuric acid (Scheme 1) [57].
We are interested in heterocyclic chemistry [60–66] and especially in the
synthesis of coumarins [67, 68]. We have also used ionic liquids as solvents and
catalysts [69–80]. In the context of consideration of green chemistry, and moving
towards rational drug design [81], recently, we have also tried to combine our
obtained experimental data, with computational analysis to interpret the experi-
mental results, or vice versa, which have been promising and fulfilled [82–87].
Due to the significance of coumarin derivatives and the importance of ionic liquids
as green catalyst/solvents and in order to support computational methods as rational
and sound tools for interpretation and also prediction of experimental data, in this
paper we wish to reveal our investigation on developing hydroarylation of cinnamic
acids with phenols mediated by acidic ionic liquid, namely N-methyl-2-pyrrolidonum
hydrosulfate ([H-NMP] HSO4) as a highly chemoselective, inexpensive commercially
available, and efficient catalyst as a mild proton source. Moreover, we have assessed
our observed experimental results on substituent effect using density functional theory
(DFT) methods [88] and quantum theory of atoms in molecules (QTAIM) approach
[89, 90] and found a reliable agreement between experimental results and our obtained
computational energetic and electronic interpretations.
Results and discussion
Initially, a mixture of cinnamic acid 1a and phenol 2a in the presence of acidic ionic
liquid [H-NMP]HSO4 was heated under reflux conditions. After a standard workup
procedure, the corresponding dihydrocoumarin 3a was obtained in 95 % yield
Scheme 1 Synthesis of ionic
liquid
123

V. Zadsirjan et al.
(Scheme 2). Encouraged by this result, we established the scope and generality of
the reaction by using differently substituted phenols (Table 1). As depicted in
Table 1, several differently substituted phenols 2a–j, bearing different groups such
as Me, Cl, and t-Bu undergo esterification with various cinnamic acids 1a–c with
subsequent intramolecular hydroarylation to give the corresponding dihydro-
coumarins 3a–j in good to excellent yields.
In this developed approach, several phenols bearing electron releasing groups
such as Me, t-Bu were easily converted into the corresponding dihydrocoumarins in
satisfactory yields in relatively short reaction times. Phenol 2a without any
substituent gave product 3a in 95 % yield. The dihydrocoumarins 3g was obtained
in 88 % using a-naphthol. Phenol with an electron withdrawing group such as the
chloro group at para position afforded the desired product 3e in high yield
(Table 1).
The suggested mechanism for the reaction of cinnamic acid with phenols
mediated by ionic liquid, involves the formation of phenolic esters via trans
esterification with subsequent intramolecular Friedel–Crafts type cyclization
resulting in the formation of corresponding dihydrocoumarin derivatives 3 [21].
Noticeably, following the aforementioned protocol, and under identical reaction
conditions, 4-nitrophenol did not produce the expected corresponding coumarin.
Actually, in the presence of [H-NMP]HSO4, under reflux conditions, the reaction of
cinnamic acid with 4-nitrophenol 2k (R = NO2) proceeded smoothly, but just
ended up in esterification to give the ester 4 (R = NO2) as sole product, the
corresponding nitro phenyl cinnamates (linear ester 4) (R = H), even after
prolonged reaction time (24 h) in low yield (35 %).
In the following section, we reveal the results of our computational studies trying
to rationalize the aforementioned observed behavior in the experimental affordance
of coumarins, using phenols, bearing CH3 as electron donating and NO2 as electron-
withdrawing groups at the para position.
Computational section
In the present section, we have concentrated on computational assessment of
substituent effects on the formation of dihydrocoumarin compounds via DFT [88]
and QTAIM [89, 90] approaches. In this respect, the reaction of para-substituted
phenols (containing CH3 as electron-donating and NO2 as electron-withdrawing
groups) with cinnamic acid have been modeled for the synthesis of dihydro-
coumarins. The aforementioned reaction model is depicted in Scheme 3.
Scheme 2 Hydroarylation of
cinnamic acid with phenols
catalyzed by ionic liquid
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
Table 1 Hydroarylation of cinnamic acid with phenols catalyzed by ionic liquid
Product (3)
Entry
Cinnamic acid (1)
Phenols (2)
Time (h) Yield %
1
5
4
95
90
1a
2a
3a
2
1a
1a
2b
2c
3b
3c
3
4
3
2
92
94
1a
1a
2d
2e
3d
3e
5
6
3
84
84
2.5
1a
1a
2f
3f
7
8
2
88
82
2g
3g
3.5
1b
2h
3h
123

V. Zadsirjan et al.
Table 1 continued
9
4.5
89
84
35
1b
2i
3i
10
11
4
1c
1a
2j
3j
4
24
2k
Scheme 3 The effective reaction models for the assessment of substituent effect
From the mechanistic point of view, the reaction of para-methyl phenol 2i with
cinnamic acid 1a leads to the formation of phenolic ester compound 5 followed by
intramolecular Friedel-Craft type cyclization to generate dihydrocoumarin 3i, while
this intramolecular cyclization step does not occur in the case of 4-nitro phenol 2k.
In this context, we have first determined the ground state structures of para-
methyl and para- nitro substituted dihydrocoumarins 3i and 3k and their
corresponding esters 5 and 4 at the M06/6-311?G** level of theory [91] with no
symmetry restrictions in geometry optimization procedure. Then, the stationary
points were analyzed by vibrational frequency calculations to confirm the found
optimized structures corresponding to true minima. It is important to mention that
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
Fig. 1 The optimized geometry
of substituted phenyl cinnamate
esters 5 and 4 and their
corresponding
dihydrocoumarins 3i and 3k
were obtained at the M06/6-
311?G* level of theory.
C3
C4
O1
C1
H1
Notably, the M06/6-311?G**
C2
H2
calculated bond length (and
bond order) values of some key
bonds have been also presented
1.34 Å(1.73)
H3
O2
Phenyl cinnamate ester
5
O2
O1
C1
C4
C2
C3
1.54 Å(0.98)
dihydrocoumarin
3i
C1
O1
C3
C4
C2
H2
H3
O2
H1
1.45 Å(1.61)
phenyl cinnamate ester
4
O1
C1
O2
C4
C2
C3
1.56 Å(0.93)
dihydrocoumarin
3k
123

V. Zadsirjan et al.
the M06 functional has been introduced as a hybrid meta-GGA (generalized
gradient approximation) exchange–correlation functional that was recommended for
application in organometallic and inorganometallic thermochemistry, kinetic
studies, and noncovalent interactions [91]. All DFT computations have been
performed using the GAMESS suite of programs [92]. In Fig. 1, we have illustrated
the theoretical optimized structures of two substituted phenyl cinnamate esters 5 and
4 and their corresponding dihydrocoumarins 3i and 3k obtained at the M06/6-
311?G** level of theory in the gas phase together with the atomic numbering. It
should be noticed that in Fig. 1, we have also presented M06/6-311?G** calculated
bond length and bond order values of some key bonds for substituted phenyl
cinnamate esters 5 and 4 and their corresponding dihydrocoumarins 3i and 3k. As it
can be seen in Fig. 1, the C=C bond (C3–C4) in para-methyl phenyl cinnamate is
richer electronically than that of para-nitro phenyl cinnamate with the higher bond
order. This electronic property significantly facilitates the intramolecular cyclization
step to produce dihydrocoumarin. On the other hand, the calculated bond order of
C2–C3 (forming via the intramolecular cyclization step) is higher in dihydro-
coumarins 3i than that of dihydrocoumarins 3k, which is in agreement with the
obtained results.
The electronic energy change values for the conversion of substituted phenyl
cinnamate esters to dihydrocoumarin compounds have been calculated at M06/6-
31G* and M06/6-311?G** levels of theory and reported in Table 2. The reported
values of electronic energy changes demonstrate that the conversion reaction in the
presence of CH3 substituent is more favorable energetically by about 2 kcal mol-1
than in the presence of NO2 substituent. It should be noted that the difference
between the values of reaction electronic energy in the presence of CH3 and NO2
substituent are approximately the same at both levels of theory, while the M06/6-
311?G** calculated reaction electronic energy is more negative than the M06/6-
31G* calculated ones. Since the difference between electronic energy of conversion
reaction is too small for description of CH3 and NO2 substituent effect, in the next
step, we focused on topological analysis of electron density via QTAIM
computations to interpret this issue more distinctly.
In this respect, the obtained M06/6-311?G** wave function files for the
optimized structures of substituted phenyl cinnamate esters 5 and 4 and their
corresponding dihydrocoumarins 3i and 3k were used as inputs to AIM2000
program [93]. Then, we calculated some selected bond and ring critical points
Table 2 The electronic energy change values for the conversion reaction of para-CH3 and para-NO2
substituted phenyl cinnamate esters to dihydrocoumarin compounds, calculated at the M06/6-31G* and
M06/6-311?G** levels of theory
Substituent
M06/6-31G*
M06/6-311?G**
CH3
NO2
-14.15
-12.18
-17.07
-15.22
Note that all values have been reported in kcal mol-1
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
(BCPs and RCPs, respectively) and their associated bond paths to assess the
conversion of substituted phenyl cinnamate esters to dihydrocoumarins from the
electronic point of view. In Table 3, we have listed the calculated values of electron
2
density, qb, its laplacian, r qb, electronic kinetic energy density, Gb, electronic
potential energy density, Vb, total electronic energy density, Hb and |Vb|/Gb of some
selected CPs for substituted phenyl cinnamate esters 5 and 4 and their corresponding
dihydrocoumarins 3i and 3k. It should be mentioned that the magnitude of q(r) and
2
the magnitude and sign of its Laplacian r q(r) at BCPs are useful indicators for the
nature of chemical bonding between atoms. Densities of local electronic energy,
H(r), its components [kinetic energy G(r) and potential energy V(r); as
H(r) = G(r) ? V(r)] and their ratio (|Vb|/Gb)at BCPs determine whether accumu-
lation of charge at a given point, r, is stabilized, H(r) \ 0, or destabilized, H(r) [ 0
[89, 90].
QTAIM molecular graphs of substituted phenyl cinnamate esters 5 and 4 and
dihydrocoumarins 3i and 3k are also presented in Fig. 2. The comparative analysis
of the reported results of Table 3 clearly shows the following facts: (1) a
comparison between the calculated electron density properties and indicators on
C3–C4 BCP in substituted phenyl cinnamate esters show that the C=C bond in para-
methyl phenyl cinnamate is electron-richer than its corresponding BCP in para-nitro
phenyl cinnamate (with 0.3342 and 0.3202 electron density values for C3–C4 BCPs
in substituted phenyl cinnamate esters 5 and 4, respectively), and, consequently, the
C=C bond in para-methyl phenyl cinnamate more readily undergoes the
intramolecular cyclization step to produce the corresponding dihydrocoumarin;
(2) at C2–C3 BCP (that is formed mechanistically through the intramolecular
cyclization step), the calculated values of q(r) in dihydrocoumarin compound 3i are
Table 3 Mathematical properties of critical points associated with the key bonds in esters and their
corresponding dihydrocoumarin compounds
2
Substituent
qb
r qb
Gb
Vb
Hb
jVbj=Gb
CH3
Cinnamate BCP(C3–C4)
Cinnamate BCP(O2–H3)
Cinnamate BCP(H1–H2)
Coumarin BCP(C2–C3)
Coumarin RCP1
0.3342
0.0182
0.0099
0.2499
0.0197
-0.9384
0.0686
0.1295
0.0148
0.0076
0.0582
0.0269
-0.4938
-0.0126
-0.0058
-0.2605
-0.0208
-0.3643
0.0022
3.8131
0.8513
0.7644
4.4759
0.7732
0.0376
0.0017
-0.5760
0.1320
-0.2023
0.0061
NO2
Cinnamate BCP(C3–C4)
Cinnamate BCP(O2–H3)
Cinnamate BCP(H1–H2)
Coumarin BCP(C2–C3)
Coumarin RCP1
0.3202
0.0199
0.0109
0.2380
0.0176
-0.9344
0.0721
0.0380
0.5764
0.1316
0.1284
0.0155
0.0076
0.0586
0.0268
-0.4906
-0.0131
-0.0058
-0.2615
-0.0207
-0.3622
0.0023
3.8208
0.8477
0.7631
4.4620
0.7723
0.0018
-0.2029
0.0061
The properties have been obtained via QTAIM analysis on the M06/6-311?G** calculated wave function
of electron density. Note that numbering of atoms is in accordance with Fig. 1
123

V. Zadsirjan et al.
Fig. 2 Complete molecular
graphs (MGs) of substituted
phenyl cinnamate esters 5 and 4
and their corresponding
C1
O1
O2
dihydrocoumarins 3i and 3k
obtained by QTAIM analysis of
M06/6-311?G** electron
density functions. Bond critical
points: red circles; ring critical
points: yellow circles; bond
paths: pink lines. (Color
C3
C4
C2
H3
H1
H2
phenyl cinnamate ester
5
figure online)
O1
O2
C1
RCP1
C4
C2
C3
dihydrocoumarin
3i
C1
O1
C3
C4
H1
C2
H2
H3
O2
phenyl cinnamate ester
4
O1
O2
C1
RCP1
C4
C2
C3
dihydrocoumarin
3k
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
larger than that of the dihydrocoumarin compound 3k that is in confirmation with
the experimental production of dihydrocoumarin 3i in high yield with the presence
of the CH3 electron-donating group at the para position of phenol; (3) a more
stringent analysis of QTAIM molecular graphs demonstrate the presence of two
C–H–H–C and C–H–O–C intramolecular interactions [94] between H1 and H2 and
also O2 and H3 in substituted phenyl cinnamate esters 5 and 4, while these H–H
and O–H bonds are not present in dihydrocoumarins 3i and 3k that confirms the
mechanistical interpretations. Moreover, the presence of H–H and O–H bonds
results in formation of additional 6-member rings with the requisite ring critical
points (RCP) very close to the BCP of H–H and O–H bonds. The comparison of the
2
corresponding values of qb and r qb for H1–H2 and O2–H3 BCPs in substituted
phenyl cinnamate esters 5 and 4 (with 0.0182 and 0.0199 qb values for O2–H3
BCPs and also 0.0099 and 0.0109 qb values for H1–H2 BCPs in substituted phenyl
cinnamate esters 5 and 4, respectively) corroborate that these C–H–H–C and
C–H–O–C intramolecular interactions are stronger in para-nitro phenyl cinnamate
4 than para-methyl phenyl cinnamate 5 and leads to the more electronic
stable para-nitro phenyl cinnamate 4. While, these C–H–H–C and C–H–O–C
intramolecular interactions in para-methyl phenyl cinnamate 5 are weaker and,
consequently, facilitate the intramolecular cyclization step to afford the respected
dihydrocoumarin 3i in high yield and (4) the intramolecular cyclization step leads
to the formation of new RCP denoted as RCP1. On the basis of the calculated
electron density values of RCP1 (with 0.0197 and 0.0176 qb values for RCP1 in
dihydrocoumarin compounds 3i and 3k, respectively), we can deduce that
formation of this new ring is more favorable in the presence of CH3 than the
NO2 substituent. Our obtained DFT and QTAIM results on energetic and electronic
features of the model reaction is in confirmation with the experimental production
of dihydrocoumarin compounds from the different para-substituted phenyl
cinnamates.
Experimental
Materials and methods
Experimental procedures and characterization
Melting points were measured by using the capillary tube method with an electro
thermal 9200 apparatus. IR spectra were recorded from a KBr disk on the FT-IR
Bruker Tensor 27. All products were known and characterized by comparison of
their IR spectra and physical data with those of authentic samples, which were
found to be identical.
Preparation of acidic ionic liquid [H-NMP]HSO4 [57]
In a 25-mL round bottom flask, a 0.97 mL (10 mmol) of 1-methyl-2-pyrrolidon in
dichloromethane (15 mL) was placed, while cooling in an ice bath and with stirring.
123

V. Zadsirjan et al.
Then 0.53 mL of sulfuric acid 98 % (10 mmol) was added drop wise to the reaction
mixture within 10 min, and stirring was continued for 4 h at ambient temperature.
The dichloromethane was removed under reduced pressure and the product was
dried at 70 °C under vacuum for 30 min in an appropriate vacuum oven.
Synthesis dihydrocoumarins: general procedure
To a 25 mL round bottomed flask equipped with a reflux condenser, phenol
(1 mmol), cinnamic acid (1 mmol), and acidic ionic liquid N-methyl-2-pyrroli-
donum hydrosulfate ([H-NMP]HSO4) (3 mmol) were placed. The reaction mixture
was heated at 120 °C for a period of time as indicated in Table 1 (2–5 h). After
completion of the reaction (monitored by TLC), the reaction mixture was cooled
and poured in water. The mixture was extracted with ethyl acetate (2 9 10 mL).
The organic layer was separated, washed with water and brine and separated again,
dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the
crude product. This crude product was column chromatographed over silica gel
(230–400 mesh) using ethyl acetate and petroleum ether as eluent to give the highly
pure products in satisfactory yield (Table 1).
Conclusion
In conclusion, we have developed a facile, operational, metal and solvent-free
reaction for hydroarylation of cinnamic acids with phenols mediated by acidic ionic
liquid N-methyl-2-pyrrolidonum hydrosulfate ([H-NMP]HSO4) affording dihydro-
coumarins 3, and 4-nitro esters 4 a, in good to high yields. Easy handling, broad
substrate scope, and the use of ionic liquid as an efficient and eco-friendly solvent
are some of the merits of our protocol. In addition, this approach can be considered
advantageous from the green chemistry point of view, since hydroarylation offers
perfect atom economy. Moreover, we have performed a comparative analysis on the
substituent effect via DFT and QTAIM approaches to interpret computationally the
experimental observations.
Experimental data
Various 4-aryl-3,4-dihydrobenzopyran-2-one derivatives and 4-nitro-phenyl
cinnamate
1. 4-Phenyl-3,4-dihydrobenzopyran-2-one (3a); [95] mp:79–81 °C; Lit. [95]
78 °C; IR (KBr): tmax = 1759 cm-1
;
1HNMR (CDCl3, 400 MHz):
d = 3.02–3.14 (m, 2H), 4.37 (t, J = 7.2 Hz, 1H), 7.00 (d, J = 7.6 Hz, 1H),
7.11 (t, J = 7.6 Hz, 1H), 7.15 (s, 1H), 8.40 (d, J = 7.2 Hz, 2H), 7.32–7.35 (m,
4H); 13CNMR (CDCl3, 100 MHz): d = 37.0 (CH2), 40.7 (CH), 117.2 (CH),
123

Hydroarylation of cinnamic acid with phenols catalyzed by…
124.7 (CH), 125.8 (Cq), 127.6 (2 9 CH), 127.7 (CH), 128.4 (CH), 128.8 (CH),
129.2 (2 9 CH), 140.3 (Cq), 151.7 (Cq), 167.7 (Cq) [38, 39].
2. 8-Methyl-4-phenyl-3,4-dihydrobenzopyran-2-one (3b); [96] mp: 107–109 °C;
1
Lit. [96] 108 °C; IR (KBr): tmax = 1764 cm-1; H NMR (CDCl3, 400 MHz):
d = 2.36 (s, 3H), 2.99–3.10 (m, 2H), 4.32 (t, J = 6.8 Hz, 1H), 6.81 (d,
J = 7.6 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 7.2 Hz, 3H), 7.26–7.33
(m, 3H); 13CNMR (CDCl3, 100 MHz): d = 15.9 (CH3), 36.9 (CH2), 40.8 (CH),
124.2 (CH), 125.6 (Cq), 125.9 (CH), 126.5 (Cq), 127.6 (2 9 CH), 127.6 (CH),
129.1 (2 9 CH), 130.3 (CH), 140.5 (Cq), 150.0 (Cq), 167.9 (Cq) [38, 39].
3. 7-Methyl-4-phenyl-3,4-dihydrobenzopyran-2-one (3c); [95] mp: 123–125 °C;
Lit. [95] 124 °C; IR (KBr): tmax = 1778, 1764 cm-1
;
1HNMR (CDCl3,
400 MHz): d = 2.38 (s, 3H), 2.99–3.11 (m, 2H), 4.33 (t, J = 6.8 Hz, 1H), 6.89
(q, J = 8.0 Hz, 2H), 6.97 (s, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.28–7.32 (m, 3H);
13CNMR (CDCl3, 100 MHz): d = 21.1 (CH3), 37.2 (CH2), 40.4 (CH), 117.5
(CH), 122.7 (Cq), 125.5 (CH), 127.6 (2 9 CH), 127.6 (CH), 128.1 (CH), 129.1
(2 9 CH), 139.2 (Cq), 140.6 (Cq), 151.6 (Cq), 167.9 (Cq) [38, 39].
4. 6-Methyl-4-phenyl-3,4-dihydrobenzopyran-2-one (3d); [97] mp:81–84 °C; Lit.
[97] 83 °C; IR (KBr): tmax = 1757 cm-1
;
1HNMR (CDCl3, 400 MHz)
d = 2.28 (s, 3H), 2.99–3.11 (m, 2H), 4.32 (t, J = 6.8 Hz, 1H), 6.81 (s, 1H),
7.05 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.18 (d, J = 7.2 Hz, 2H),
7.29–7.40 (m, 3H); 13CNMR(CDCl3, 100 MHz): d = 20.8 (CH3), 37.2 (CH2),
40.7 (CH), 116.9 (CH), 125.3 (Cq), 127.6 (2 9 CH), 127.6 (CH), 128.7 (CH),
129.2 (2 9 CH), 129.3 (CH), 134.4 (Cq), 140.5 (Cq), 149.7 (Cq), 167.9 (Cq)
[38, 39].
5. 43.1.12.
6-Chloro-4-phenyl-3,4-dihydrobenzopyran-2-one
(3e);
[98]
1H
mp:102–105 °C; Lit. [98] 103–104 °C; IR (KBr): tmax = 1770 cm-1
;
NMR (CDCl3, 400 MHz): d = 3.00–3.12 (m, 2H), 4.33 (t, J = 6.8 Hz, 1H),
6.96 (s, 1H), 7.10 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 7.6 Hz, 2H), 7.30 (s, 1H),
7.35–7.40 (m, 3H); 13CNMR (CDCl3, 100 MHz): d 36.6 (CH2), 40.6 (CH),
118.5 (CH), 127.5 (2 9 CH), 127.6 (Cq), 128.0 (CH), 128.2 (CH), 128.9 (CH),
129.4 (2 9 CH), 129.8 (Cq), 139.4 (Cq), 150.2 (Cq), 166.9 (Cq) [38, 39].
6. 7,8-Benzo-4-phenyl-3,4-dihydrobenzopyran-2-one (3g); [96] mp: 111–113 °C;
1
Lit. [96] 112 °C; IR (KBr): tmax = 1762 cm-1; HNMR (CDCl3, 400 MHz):
d = 3.14–3.26 (m, 2H), 4.51 (s, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.20 (d,
J = 6.4 Hz, 2H), 7.32 (s, 1H), 7.35 (d, J = 6.8 Hz, 2H), 7.57 (s, 1H), 7.60 (d,
J = 10.4 Hz, 2H), 7.85 (d, J = 7.2 Hz, 1H), 8.33 (d, J = 7.6 Hz, 1H);
13CNMR (CDCl3, 100 MHz): d = 37.3 (CH2), 41.1 (CH), 119.9 (Cq), 121.4
(CH), 123.7 (Cq), 124.3 (CH), 125.3 (CH), 126.8 (CH), 126.9 (CH), 127.5
(2 9 CH), 127.6 (CH), 127.7 (CH), 129.2 (2 9 CH), 133.7 (Cq), 140.7 (Cq),
146.8 (Cq), 167.5 (Cq) [38, 39].
7. 4-Nitro-phenyl cinnamate (4) [35]; mp: 143–145 °C; Lit [35] 142–146 °C; IR
(KBr): tmax = 1735 cm-1
; d 6.56 (d,
1HNMR (CDCl3, 400 MHz):
J = 16.0 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.37–7.39 (m, 3H), 7.53–7.55
(m, 2H), 7.85 (d, J = 16.0 Hz, 1H), 8.24 (d, J = 8.8 Hz, 2H); 13CNMR
(CDCl3, 100 MHz): d 115.1 (CH), 121.4 (2 9 CH), 124.2 (2 9 CH), 127.5
123

V. Zadsirjan et al.
(2 9 CH), 128.1 (2 9 CH), 130.2 (CH), 132.7 (Cq), 144.2 (Cq), 147.0 (CH),
154.6 (Cq), 163.3 (Cq) [38, 39].
Acknowledgments The authors thank the Alzahra Research Council for support.
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