RETRACTED ARTICLE: Boric acid in magnetized water: Clean and powerful media for synthesis of 3,4-dihydropyrimidin-2(1: H)-ones

Article abstract of DOI:10.1039/d1ra03769b

Water was magnetized via an external magnetic field and employed, for the first time, as a solvent in green preparation of 3,4-dihydropyrimidin-2(1H)-ones by the one-pot three-component condensation reaction using boric acid as a catalyst. Shorter reactio

Full text of DOI:10.1039/d1ra03769b

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Boric acid in magnetized water: clean and powerful
media for synthesis of 3,4-dihydropyrimidin-2(1H)-
ones†
Cite this: RSC Adv., 2021, 11, 22751
a
b
Sahra Sheikhaleslami,a
*
Vahid Khakyzadeh,
Ahmad Reza Moosavi-Zare,
Amir Ehsani,a Salbin Sediqi,a Mohammad Rezaei-Goharb and Zahra Jalilianc
Received 14th May 2021
Accepted 22nd June 2021
Water was magnetized via an external magnetic field and employed, for the first time, as a solvent in green
preparation of 3,4-dihydropyrimidin-2(1H)-ones by the one-pot three-component condensation reaction
using boric acid as a catalyst. Shorter reaction times, higher yields, and cleaner reaction profiles were some
advantages of using magnetic water.
DOI: 10.1039/d1ra03769b
rsc.li/rsc-advances
It is well-known that water is the most crucial matter in nature, the water molecules, the magnetic eld will directly affect the
thus in numerous papers, physical and chemical properties of nature of the water molecules, the third mechanism is largely
water and also their changes under actions of external factors consistent with the experiments performed.7 Recently, few
like electromagnetic elds have been investigated,1 although research groups such as Alabi, Zuniga, and Rodgers have started
the principle of magnetic eld (MF) treatment on the water is to examine the magnetic eld effects on chemical reactions and
still a controversial subject, and no clear mechanisms of this their consequences in yield and rate of reaction or product
effect have been reported in the literature.2 Many studies have distribution. It was considered that these effects might be per-
indicated that the physicochemical properties of water change formed via the radical pair mechanism.8
by passing through the MF,3 for example, inter- and intra-
Encouraged by previous works in the application of magnetic
cluster hydrogen bonds, coagulation, polymorphism of the water, we decided to produce and employ magnetic water as
crystals, the zeta potential of the precipitated or dispersed a solvent in some interesting organic reactions.9 The multi-
particles, viscosity, diffusivity, surface tension, friction coeffi- component condensation reactions are valuable protocols for
cient, pH values, electrical conductivity, and some physical synthesizing desired compounds in one step without the sepa-
properties of water, including specic heat, evaporation ration of any intermediates in organic chemistry.10 In this
amount and boiling point.4 Owing to the changes in physico- chemical strategy, some benecial features are high yields,
chemical properties, magnetic water has been utilized mainly shorter reaction times, high atomic economy, and low waste
for agriculture, wastewater treatment, industry, and construc- materials and energy consumption.11 So staying in this direc-
tion.5 The magnetization of water and its effectiveness on the tion can bring us closer to the goals of green chemistry.12
physical and chemical properties of water depends on several Preparation of 3,4-dihydropyrimidin-2(1H)-one (DHPMs) is
factors including, magnetization and exhibition of a magnetic signicant due to their therapeutic and pharmacological prop-
eld, magnetic gradient, Lorentz force, and magnetic memory.6 erties, for example; Batzelladine, found in marine natural
Three mechanisms have been proposed for how the magnetic alkaloids, as an HIV inhibitor,13a also monastrol,13b and SQ
eld affects water particles: (I) the spontaneous formation and 32926,13c have been explained as synthetic or natural DHPs with
collapse of cationic metal colloidal units in the interaction of biological properties (Scheme 1). The Biginelli reaction was re-
magnetism and water, which leads to increase sedimentation in ported for the rst time by Pietro Biginelli.14 In this reaction,
water; (II) the change in polarization of the dissolved ions in the 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) were prepared by
water, the shape and size of the hydration layer cause some a three-component condensation reaction of aldehyde, urea,
variations in the water properties; and (III) due to the polarity of
aDepartment of Chemistry, K. N. Toosi University of Technology, P.O. Box 16315-1618,
15418 Tehran, Iran. E-mail: v.khakyzadeh@kntu.ac.ir
bHamedan University of Technology, Department of Chemistry, Hamedan, 65155, Iran
cChemistry Department, College of Science, University of Kurdistan, Pasdaran Street,
Sanandaj, 66177-15177, Iran
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d1ra03769b
Scheme 1 DHPMs containing natural or synthetic parts.
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in presenting this result. A paramagnetic structure with
magnetic properties is more soluble in a magnetized solvent.29
Next, the viscosity, as an essential factor in the efficiency of
organic reaction, was measured at different temperatures
according to the reference method.30 The results determined
that the viscosity of magnetic water was generally slightly lower
than ordinary distilled water. Based on our observations, it was
found that the viscosity differences were higher at low temper-
atures, indicating that at high temperatures, the hydrogen
bonds are almost weakened and results in no signicant
differences between the viscosity of magnetic water and ordi-
nary water. In contrast, at low temperatures, because of the high
number of intra-cluster bonds in ordinary water, they form
a colloidal bulk structure that increases its viscosity. The
intermolecular structure of the magnetic water molecules is
hexagonal layers that are interconnected by inter-cluster
hydrogen bonds, which form a graphite-like structure and
gives a particular soness to the water and reducing its viscosity
(Fig. 1a).31 This property could be effective in running the
organic reaction. Moreover, the refractive index of magnetic
water and nonmagnetic water was also evaluated by a refrac-
tometer at different temperatures. It was found that at low
temperatures, the refractive index of magnetic water was
approximately the same as distilled water, whereas, at higher
temperatures, the refractive index of magnetic water was lower
than ordinary water. To justify this observation, it can be noted
that magnetic water has a more stable structure than ordinary
water, and this somewhat stable structure limited waste frac-
tures when the photons traveled through the water (Fig. 1b).
Interestingly, our results were contrary to Hosoda et al. who
showed magnetic water has a higher refractive index.32 They
explained that it is because of the lifetime of the H-bonds. pH
measurements can also be evaluated as a criterion for investi-
gating hydrogen bond clusters. For this issue in mind, the pH
changes of the water were measured at different temperatures.
It was found that the acidity of the magnetic water was lower
than ordinary water, and the difference between their pH
enhanced with increasing temperature (Fig. 1c). Surface tension
analysis for magnetized water and distilled water showed that
ordinary water has a higher surface tension in different
Scheme 2 The one-pot three-component preparation of 3,4-dihy-
dropyrimidin-2(1H)-ones in magnetized water/B(OH)3 system.
and ß-ketoester as interesting compounds with a potential for
pharmaceutical applications. Various catalysts were reported for
this reaction such as, [bmim][MeSO4],15 FeCl3,16 RuCl3,17 TMSCl,18
ZrSA19 and [H-NMP][CH3SO3].20 Due to the important properties of
these compounds, nding the new protocols for the synthesis of
3,4-dihydropyrimidin-2(1H)-ones are still needed.
Nowadays, many reactions need catalysts to carry out.
Among many kinds of them, organocatalysts have attracted
much attention. They are well-known as articial catalysts for
these plans. In comparison with inorganic catalysts and
enzymes, they are not complicated, regularly less toxic, and
widely available.21 Boric acid, as an organocatalyst, aqueous
solution system, is one of the efficient and green catalytic systems
in organic chemistry. Boric acid was successfully utilized in the
preparation of different organic compounds such as, pyrano[2,3-d]
pyrimidine diones,22 tetrahydrobenzo[b] pyrans,23 N,N0-alkylidene
bisamides,24
4H-isoxazol-5-ones,25
2-arylamino-2-phenyl-
acetamide,26 bis(indolyl)methanes.27 In these mild conditions, H+,
which is abstracted from water by the interaction with B(OH)3,
efficiently catalyzes the reaction,22,23 and water as a solvent plays
a key role in these reactions. In water molecules, the non-uniform
distribution of electrons leads to the creation of positive and
negative particle charges. Based on points mentioned earlier, we
wondered to evaluate the effect of magnetized water as a solvent
and also using boric acid as a catalyst, on the synthesis of 3,4-
dihydropyrimidin-2(1H)-one derivative (Scheme 2).
To prepare magnetic water, a cylindrical system with an
approximate capacity of 100 mL was lled with neodymium super-
magnets (Nd), which generated a magnetic eld of 130 mT at the
center and diameter of the tube, was used to construct the reactor
of magnetic water. The water used in the system was distilled twice
by the Prima30 machine and circulated in the system by a (SEBO P-
280) pump with a power of 200 liters per hour, and aer 8 hours,
the water became magnetic. Aer the preparation of magnetic
water, some main physicochemical properties, such as viscosity,
gas solubility, refractive index, surface tension, pH, UV-visible and
FT-IR analysis, were evaluated.
Initially, the oxygen gas solubility in magnetic and ordinary
water was measured by Winkler method based on standard
method procedure.28 Aer photometric testing, it was found
that the solubility of oxygen in magnetic water was slightly
higher than in ordinary water (MW : n-MW ¼ 8 : 7 ppm). We
suggested that probably the paramagnetism of oxygen struc-
ture, as well as the molecular orbital of oxygen, can be effective
Fig. 1 The viscosity, refractive index, pH measurements, and surface
tension analysis for magnetic and distilled water in different
temperatures.
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Fig. 2 Scope of the synthesis of 3,4-dihydropyrimidin-2(1H)-ones in magnetized and distilled water as solvent under optimized condition.19,34–36
temperatures rather than magnetic water which was in good optimized conditions, we have chosen the reaction of ethyl
agreement with Cho's report that magnetic eld reduced the acetoacetate (1 mmol), urea (1 mmol), and benzaldehyde (1
surface tension of natural water by about 8% (Fig. 1d).33
Eventually, for examining the optical properties of magnetic
mmol) as a model reaction (Table 1).
This reaction was investigated in the presence of different
and ordinary water, IR and UV analyses were performed. No amounts of boric acid at temperatures ranging between 25 ꢀC and
signicant difference was detected in the UV spectra (ESI, S1†), 100 ꢀC under aqueous conditions (entry 1–12). At rst, in the
but, interestingly, in the IR spectra, some peaks were weakened or model reaction without catalyst and solvent at 80 ꢀC, a trace yield
disappeared, and some new peaks were observed (ESI, S2†). There was observed (entry 1). Then we checked different amounts of the
are two differences in comparing ordinary and magnetic water IR boric acid as a catalyst (entry 2–5, 3–15 mol%) in water, and 75% of
spectra: (I) the detection of Peaks 2923.53 and 2853.03 is probably desired product was seen when we employed a 15 mol% catalyst.
due to internal structural patterns of H2O molecules and/or Aer that, the reaction was carried out at different temperatures
hydrogen bond chain in ordinary water which in magnetic water (entry 6–8). No improvement was recognized at 100 ꢀC. Next,
these peaks are very weakened or not seen due to the new struc- magnetized water was employed as a solvent in the model reaction
tural patterns of water molecules; (II) in the 1709.69 region, a new with a similar condition of entry 5. Interestingly, shorter reaction
peak was detected in the magnetic water spectrum compared to time and higher yield were obtained (entry 9, 15 min: 95%),
ordinary water, which was attributed to the transition of the water compared to distilled water and ethanol. Moreover, the model
phase from a complex irregular spherical structure to a regular reaction was evaluated in some organic solvents such as n-hexane,
hexagonal ring structure in magnetic water (Fig. 3).
Aer preparation and characterization of magnetic water, we with water, no better results were seen (entry 10–12).
wonder to investigate the preparation of 3,4-dihydropyrimidin- To investigate the efficacy and generality of boric acid in the
dichloromethane, and ethanol under reux conditions compared
2(1H)-ones using boric acid, in nonmagnetic water and also synthesis of 3,4-dihydropyrimidin-2(1H)-ones, various aryl aldehydes
magnetic water as solvent under reux conditions. To nd were reacted with ethyl acetoacetate and urea using boric acid
aqueous solution (magnetized water and distilled water) system
under the optimal reaction conditions to obtain the desired prod-
ucts in high yields and in short reaction times. The highest reaction
yields have been detected in para-substituted aryl aldehydes with
halogen [–F (96%), –Cl (96%), –Br (96%)], whereas disubstituted aryl
aldehyde with halogen has shown the lowest reaction yield (90%).
Also, aryl aldehydes with electron-donating substitutions displayed
lower reaction yields [–OH (92%), –OCH3 (92%)] (Fig. 2).
The acidity of the aqueous boric acid solution is exclusiveꢁly
due to the reaction of boric acid with water to prepare B(OH)4
.
It can release of H+ in the aqueous solution.22,23 In the proposed
mechanism, which is supported by the literature,19,20,30–32 at rst,
Fig. 3 Schematic diagram of the FTIR spectroscopy of magnetized
and distilled water.
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Table 1 The effect of catalyst amounts, temperature, and various
solvents on the reaction of ethyl acetoacetate, urea, and benzaldehyde
as a model reaction
Notes and references
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Entrya
Catalyst (mol%)
Solvent
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
—
3
5
—
H2O
H2O
H2O
180
55
40
30
22
60
40
22
15
40
40
35
Trace
45
50
60
75
25
45
78
95
10
15
15
15
15
15
15
15
15
H2O
H2Oc
H2Od
H2Oe
m-H2O
n-Hexane
CH2Cl2
Ethanol
9
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11
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15
35
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50 ꢀC. e At ¼ 100 ꢀC.
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3,4-dihydropyrimidin-2(1H)-ones
´
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Conclusions
Herein, we have investigated the employment of magnetized water
as a reaction media to prepare 3,4-dihydropyrimidin-2(1H)-ones by
a one-pot three-component condensation reaction using a boric acid
catalyst and compared the results with non-magnetic media for the
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Conflicts of interest
There are no conicts to declare.
ˆ
L. K. Kohn, M. A. Antonio and J. E. De Carvalho, Bioorg.
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and Hamedan University of Technology, for nancial support of
the presented work.
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