A highly efficient and green protocol for the synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone) derivatives catalyzed by a dicationic molten salt

Article abstract of DOI:10.1515/znb-2020-0174

A highly efficient and green protocol for the synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone) {3,3′-(arylmethylene)-bis(2-hydroxynaphthalene-1,4-dione)} derivatives has been developed. The reaction of 2-hydroxynaphthoquinone (2-hydroxynapht

Full text of DOI:10.1515/znb-2020-0174

Z. Naturforsch. 2021; 76(2)b: 91–95
Abdolkarim Zare* and Aysoda Ghobadpoor
A highly efficient and green protocol for the
synthesis of 3,3′-(arylmethylene)-
bis(2-hydroxynaphthoquinone) derivatives
catalyzed by a dicationic molten salt
https://doi.org/10.1515/znb-2020-0174
4-nitrobenzaldehyde. Some catalysts have been reported
Received September 21, 2020; accepted December 12, 2020;
published online January 14, 2021
for this transformation [11–18]. It is noteworthy that only
a few catalysts have been reported for the preparation
of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone)
derivatives from 2-hydroxynaphthoquinone (2 eq.) and
arylaldehydes (1 eq.). Therefore, it is highly desirable to
develop new efficient catalysts for this transformation.
Salts which comprise organic cations and organic/
inorganic anions, and melt below 100 °C are defined as
ionic liquids, whereas salts which contain organic/inor-
ganic cations and anions, and melt above 100 °C are
commonly referred to as molten salts (MSs) [19]. MSs have
a wide range of chemical and industrial applications.
For instance, they have been utilized as catalysts [19–25]
and reaction medium [26–31] in chemical reactions. MSs
have been also applied as electrolyte in rechargeable zinc-air
batteries [32], and tubular-receiver for solar power tower [33].
Furthermore, they have been used for separation [34], heat
transfer [35], and thermal energy storage [36].
Abstract: A highly efficient and green protocol for
the synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaph-
thoquinone) {3,3′-(arylmethylene)-bis(2-hydroxynaph-
thalene-1,4-dione)} derivatives has been developed. The
reaction of 2-hydroxynaphthoquinone (2-hydroxynaph-
thalene-1,4-dione) (2 eq.) and arylaldehydes (1 eq.) in the
presence of the dicationic molten salt N,N,N′,N′-tetrame-
thylethylenediaminium bis-hydrogensulfate ([TMEDAH2]
[HSO4]2) under solvent-free conditions afforded the mentioned
compounds in high yields and relatively short reaction times.
Keywords: 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone)
{3,3′-(arylmethylene)-bis(2-hydroxynaphthalene-1,4-dione)};
dicationic molten salt; N,N,N′,N′-tetramethylethylenediami-
nium bis-hydrogensulfate ([TMEDAH2][HSO4]2); solvent-free.
Solvent-free condition is a practical and well-known
technique in organic synthesis. The superiority of this
technique with respect to reactions in solution consists of
compliance with green chemistry principles. Safer reaction
profiles, facile workup, easier procedures for purifying the
products, higher yield and selectivity of products, shorter
reaction times, less energy consumption, and prevention
or decrease of by-products/waste formed [37–42] are often
realized advantages.
In this work, we have utilized a dicationic molten
salt namely N,N,N′,N′-tetramethylethylenediaminium bis-
hydrogensulfate ([TMEDAH2][HSO4]2) as highly efficient
catalyst for the synthesis of 3,3′-(arylmethylene)-bis(2-
hydroxynaphthoquinone) derivatives through the reac-
tion of 2-hydroxynaphthoquinone (2 eq.) with arylalde-
hydes (1 eq.) under solvent-free conditions.
1 Introduction
Compounds bearing a naphthoquinone moiety are of
great importance in medicinal and biological chemistry
[1–10]. They have shown a wide range of medicinal and
biological activities, such as antimalarial [2], antitumor [3],
antimicrobial [4], anti-inflammatory [5], antibacterial [6],
antiproliferative [7], CDC25 phosphatase inhibitor [8],
antifungal [9], antiplatelet [10], and antiallergic [10] properties.
A special class of these compounds is 3,3′-(arylmethylene)-
bis(2-hydroxynaphthoquinone) {3,3′-(arylmethylene)-bis(2-
hydroxynaphthalene-1,4-dione)} derivatives, which could be
prepared through the reaction of 2-hydroxynaphthoquinone
(2-hydroxynaphthalene-1,4-dione) (2 eq.) and arylaldehydes
(1 eq.). See Scheme 1 for the respective reaction with
*Corresponding author: Abdolkarim Zare, Department of Chemistry,
Payame Noor University, P. O. Box 19395‐3697 Tehran, I. R. Iran,
E-mail: abdolkarimzare@pnu.ac.ir
Aysoda Ghobadpoor, Department of Chemistry, Payame Noor
University, P. O. Box 19395-3697 Tehran, I. R. Iran
2 Results and discussion
First, the reaction conditions were optimized by study-
ing the influence of the amount of catalyst and the

92
A. Zare and A. Ghobadpoor: Synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone) derivatives
Scheme 1: The reaction of 2-hydroxynaphthoquinone
with 4-nitrobenzaldehyde.
Table : Optimization of the reaction conditions of the condensa-
tion of -hydroxynaphthoquinone ( mmol) with
-nitrobenzaldehyde.
amount of catalyst was increased up to 27 mol% and the
temperature was raised up to 125 °C. However, no
improvement of the reaction time and yield was observed
under these conditions (Table 1, entries 3 and 5).
Entry
Mol% of [TMEDAH] Temp. (°C) Time (min) Yielda (%)
Efficiency and generality of our protocol for the synthesis
[HSO]
of
3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone)






















derivatives were assessed by the reaction of
 2-hydroxynaphthoquinone with diverse arylaldehydes,

ranging from unsubstituted benzaldehyde to aromatic
aldehydes bearing electron-releasing, electron-attracting,

aIsolated yields.
and halogen substituents. The results obtained in these
experiments are given in Table 2. The very good results
(i.e., production of the products in good to excellent yields
and relatively short times) confirmed the high efficiency
and generality of the protocol. It should be mentioned that
reactions with aliphatic aldehydes are planned.
Because of the coexisting weakly acidic and basic
groups in the structure of [TMEDAH2][HSO4]2 (the hydrogen
and oxygen atoms of hydrogensulfate are acidic and
weakly basic, respectively, [TMEDAH2]2+ is weakly acidic),
it can act as a dual-functional (acid-base) catalyst. Given
this and based on arguments put forward in the literature
[14–16], a plausible mechanism was proposed for the
temperature on a model reaction, the condensation
of 2-hydroxynaphthoquinone (2 mmol) with
4-nitrobenzaldehyde (1 mmol) (Scheme 1). The results are
summed up in Table 1. As the data illustrate, the reaction
using 20 mol% of [TMEDAH2][HSO4]2 at T = 120 °C lead
to the desired product in only moderate yield (Table 1,
entry 1). Examining the model reaction in the presence of
25 mol% of the molten salt at 115 °C also did not give
satisfactory results (Table 1, entry 4). The best results were
obtained when 25 mol% of the catalyst was employed at
120 °C (Table 1, entry 2). To improve the results, the
Table : The synthesis of ,′-(arylmethylene)-bis(-hydroxynaphthoquinone) derivatives catalyzed by [TMEDAH][HSO].
Product No.
Ar
Time (min)
Yielda (%)
M.p. (in °C) found (reported) [ref.]

CH




















– (–) []
– (–) []
– (–) []
– (–) []
– (–) []
– (–) []
– (–) []
– (–) []
– (–) []
– (–) []

-CHCH
,-(CHO)CH
-CHOCH
-ONCH
-ONCH
-ClCH
-ClCH
,-ClCH
-FCH








aIsolated yields.

A. Zare and A. Ghobadpoor: Synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone) derivatives
93
Scheme 2: The proposed reaction mechanism.
reaction (Scheme 2). The catalyst tasks are clearly reflected and 3. The dual functionality of catalysts possessing
in this mechanism. The acidic hydrogen can activate the hydrogensulfate (or similar anions) has been discussed in
electrophiles to accept nucleophilic additions in steps 1 the literature [20, 43].
and 3. Additionally, the acidic group can facilitate removal
The reaction conditions and the results of [TMEDAH2]
of H2O in step 2, and tautomerization in step 4. The basic [HSO4]2 for the synthesis of compound 1 were compared
oxygen can activate the nucleophiles to perform steps 1 with those of other reported catalysts (Table 3). As Table 3
Table : The preparation of compound  using [TMEDAH][HSO] and the reported catalysts.
Catalyst
Conditions
Time (min)
Yield (%)
Ref.
[TMEDAH][HSO]
LiCl
LiCl
HSO
LiCl
Lipase
O-Carboxymethyl chitosan
HO-[bmim][BF]a, b
Sulfamic acid
Solvent-free,  °C
HO,  °C, ultrasonic irradiation
HO,  °C, microwave irradiation
HO-EtOH, reflux
HO, reflux




–
[]
[]
[]
[]
[]
[]
[]
[]






EtOH,  °C


HO-MeOH,  °C
 °C


–

–

HO-EtOH, r.t.
aAqueous -Butyl--methylimidazolium tetrafluoroborate. bIn this work [], the particular synthesis of compound  has not been reported.
Therefore, the ranges of the reaction times and yields as given in the study by Li et al. [] have been tabulated here.

94
A. Zare and A. Ghobadpoor: Synthesis of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone) derivatives
indicates, the yields with [TMEDAH2][HSO4]2 as catalyst in
our work were higher than with other catalysts, and the
reaction times were shorter than with most of the other
reported catalysts. Additionally, the reaction has been
carried out under solvent-free conditions in our work.
However, the reaction temperature in our work is higher
than in the other catalytic systems employed due to the
higher melting point of [TMEDAH2][HSO4]2.
4.2 General procedure for the synthesis
of 3,3′-(arylmethylene)-
bis(2-hydroxynaphthoquinone)
derivatives
A mixture of 2-hydroxynaphthoquinone (2 mmol), alde-
hyde (1 mmol) and [TMEDAH2][HSO4]2 (0.25 mmol, 0.078 g)
was vigorously stirred by a small rod at T = 120 °C. Upon
completion of the reaction as indicated by TLC (eluted by n-
hexane-ethyl acetate: 2:1, v/v), the reaction mixture was
cooled to room temperature, and the resulting precipitate
was recrystallized from hot ethanol-H2O (7:3, v/v) to afford
the pure product.
3 Conclusion
In summary, we have developed a new protocol for the prep-
aration of 3,3′-(arylmethylene)-bis(2-hydroxynaphthoquinone)
derivatives using a dicationic molten salt as a dual-
functional catalyst. The promising points of this protocol
include high yields, relatively short reaction times, gener-
ality, efficiency, easy preparation of the catalyst, simple
workup, facile purification of the products by recrystalliza-
tion, solvent-free reactions and, hence, good agreement
with green chemistry principles.
5 Supplementary Material
Selected spectral data and original spectra of the synthe-
sized 3,3′v-(arylmethylene)-bis(2-hydroxynaphthoquinone)
derivatives are given as Supplementary Material available
online (https://doi.org/10.1515/znb-2020-0174).
Author contributions: All the authors have accepted
responsibility for the entire content of this submitted
manuscript and approved submission.
4 Experimental section
Research funding: We thank Research Council of Payame
Noor University for the support of this work.
4.1 Materials and instruments
Conflict of interest statement: The authors declare no
conflicts of interest regarding this article.
The reactants and solvents were purchased from Fluka
or Merck Chemical Companies. [TMEDAH2][HSO4]2 was
prepared according to our published method (Scheme 3)
[20]. For the identification of the products, their melting
points/spectral data were compared with those reported in
the literature. Thin-layer chromatography (TLC) using
silica gel SIL G/UV 254 plates was utilized for observing
progress of the reactions. FT-IR spectra were recorded by a
Shimadzu IR-60 instrument. 1H NMR (400 or 500 MHz) and
13C NMR (100 or 125 MHz) were run on Bruker Avance DPX,
FT-NMR spectrometers. Melting points were measured us-
ing a Thermo Scientific 9200 instrument in open capillary
tubes. Mass spectra were obtained with Shimadzu GC-MS-
QP 1100 Ex.
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