Deep eutectic solvents used as catalysts for synthesis of 1,10-phenanthroline by improved Skraup reaction

Article abstract of DOI:10.1007/s11164-021-04482-y

Abstract: In this study, three different choline chloride-based deep eutectic solvents were synthesized. And it is the first time to synthesize 1,10-phenanthroline through an improved Skraup reaction using deep eutectic solvent as the new catalyst from acrolein and 8-aminoquinoline. The deep eutectic solvents were characterized by Fourier transform infrared (FT-IR), ¹H nuclear magnetic resonance (¹H NMR), pH/mV meter, and thermogravimetric analysis (TGA). The research results show that the deep eutectic solvent formed by sulfanilic acid and choline chloride has the strongest acidity and highest catalytic active among the three deep eutectic solvents. Besides, the impacts of reaction parameters and molar ratio of raw materials on the reaction were also investigated. Under the optimized reaction conditions, the maximum selectivity and yield of 1,10-phenanthroline were achieved as 84.6 and 75.6%, respectively. The synthesis method, meanwhile, also has simple preparation process and low cheaper catalyst raw. Graphical abstract: [InlineMediaObject not available: see fulltext.] Replacing traditional sulfuric acid and hydrochloric acid with deep eutectic solvents (DESs) as new catalysts provides a more efficient, greener and more economical strategy for the synthesis of 1,10-phenanthroline by a new improved Skraup reaction.

Full text of DOI:10.1007/s11164-021-04482-y

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04482-y
Deep eutectic solvents used as catalysts for synthesis
of 1,10‑phenanthroline by improved Skraup reaction
Mingliang Wu, et al. [full author details at the end of the article]
Received: 10 March 2021 / Accepted: 24 April 2021
©
The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
In this study, three diferent choline chloride-based deep eutectic solvents were
synthesized. And it is the ꢀrst time to synthesize 1,10-phenanthroline through an
improved Skraup reaction using deep eutectic solvent as the new catalyst ꢁrom acr-
olein and 8-aminoquinoline. The deep eutectic solvents were characterized by Fou-
1
1
rier transꢁorm inꢁrared (FT-IR), H nuclear magnetic resonance ( H NMR), pH/mV
meter, and thermogravimetric analysis (TGA). The research results show that the
deep eutectic solvent ꢁormed by sulꢁanilic acid and choline chloride has the strongest
acidity and highest catalytic active among the three deep eutectic solvents. Besides,
the impacts oꢁ reaction parameters and molar ratio oꢁ raw materials on the reac-
tion were also investigated. Under the optimized reaction conditions, the maximum
selectivity and yield oꢁ 1,10-phenanthroline were achieved as 84.6 and 75.6%,
respectively. The synthesis method, meanwhile, also has simple preparation process
and low cheaper catalyst raw.
Vol.:(012
1
3456789)
3

M. Wu et al.
Graphical abstract
Replacing traditional sulꢁuric acid and hydrochloric acid with deep eutectic solvents
(
DESs) as new catalysts provides a more eꢂcient, greener and more economical
strategy ꢁor the synthesis oꢁ 1,10-phenanthroline by a new improved Skraup
reaction.
Keywords Skraup reaction · 1,10-phenanthroline · Deep eutectic solvent · Choline
chloride · Acrolein · 8-aminoquinoline
Introduction
1
,10-phenanthroline has been used ꢁor decades as a class oꢁ important nitrogen het-
erocyclic and chelating agents that ꢁorm a multitude oꢁ coordination compounds
with various metal ions [1]. By ꢁar, the researchers show a great interest in the
supramolecular chemistry [2], pharmaceutical chemistry [3], catalytic chemistry [4]
and organic ꢁunctional materials [5] on 1,10-phenanthroline.
Due to the signiꢀcant applications oꢁ 1,10-phenanthroline in the ꢀelds oꢁ
chemistry and biology, some classic synthesis methods oꢁ 1,10-phenanthroline
include Skraup [6], Friedlander [7] and Doebner-Von Miller [8] reactions. Oth-
erwise, Povarov reaction [9] and photochemical electrocyclic reaction [10], in
recent years, have also been as novel methods to the synthesis oꢁ 1,10-phenanth-
roline. These methods, however, usually carried out under harsh conditions such
as strong acidity and high temperature so that it is diꢂcult to control the reaction.
More terribly, what are the limitations oꢁ these methods are complex reaction
process, low yield, poor selectivity, and high corrosive. Thus, the development
oꢁ eꢂcient synthetic method ꢁor the preparation oꢁ 1,10-phenanthroline with
mild reaction conditions is still a challenge problem. Chelucci et al. [11] stud-
ied the synthesis oꢁ 1,10-phenanthroline, with the yield oꢁ it reaching 67%, ꢁrom
1
3

Deep eutectic solvents used as catalysts for synthesis of…
polysubstituted pyridine as the original materials in a two-step process. Later,
Abahmane et al. [12] investigated that the alumina-supported gold nanoparti-
cles catalyzed the 1,2-cyclohexanedione and propargylamine toward synthesis oꢁ
1
,10-phenanthroline with a yield oꢁ 75%. Furthermore, Cheng et al. [13] reported
that an efective method to synthesis oꢁ a series oꢁ 1,10-phenanthroline deriva-
tives by the Lewis acid-catalyzed cyclization reaction between 3-ethoxycyclobu-
tanones and 8-aminoquinolines. In those studies, however, they ofered some new
routes ꢁor the synthesis oꢁ 1,10-phenanthroline and could obtain a certain yield oꢁ
it, but most oꢁ them used the expensive raw materials and catalysts, which have
a higher reaction cost so that it is not suitable ꢁor large-scale industrial produc-
tion. So, we ꢁocused on the synthesis oꢁ 1,10-phenanthroline with simple meth-
ods and original materials. At the same time, what we considered was that the
structural ꢁramework oꢁ 1,10-phenanthroline could not contain any substitution
groups. So, the 8-aminoquinoline(8-AQ) was used as the ring-ꢁorming ꢁramework
structure. Acrolein, in the Skraup reaction, glycerol was dehydrated under strong
acid reaction conditions to ꢁorm it [14], 15, was used ꢁor cyclization reaction.
Based on the above researches, it is clear that the development oꢁ an available
catalyst with high activity and low cost maintains a challenge. Since the term
deep eutectic solvent (DES) was proposed in 2001 by Abbott et al. [16], basic
properties and potential applications oꢁ these systems have been investigated. At
the same time, many researchers used the DESs as dual roles (solvent and cata-
lyst) in many reactions. Otherwise, DESs are now as a new type oꢁ ionic liquid
(
IL) analogs, which have many similar properties and characteristics with ILs: a
low vapor pressure, a relatively excellent chemical and thermal stability, strong
solubility and modiꢀability [17]. However, ILs are ꢁormed ꢁrom systems consisted
mainly oꢁ a type oꢁ discrete anion and cation. In contrast, DESs contain a hydro-
gen bond acceptor (HBA) and a hydrogen bond donor (HBD), mixed together to
ꢁ
orm a homogeneous system. What is more, the process oꢁ the preparation ꢁor
DESs is simple and high atom economy and the raw materials are cheap, which
is beneꢀcial ꢁor large-scale production. Shahabi et al. [18] researched that using
choline chloride/tin(II) chloride DES as a green catalyst, under a relatively mild
reaction conditions, ꢁor the synthesis oꢁ quinoline with the yield was as high as
9
2% through a one-pot, three components. However, there are no reports in the
literature that using DES as a catalyst ꢁor the synthesis oꢁ 1,10-phenanthroline.
So, in this study, three diferent DESs were prepared by simple mixed heating
HBDs oꢁ sulꢁamic acid, aminomethane sulꢁonic acid, sulꢁanilic acid and the same
HBA choline chloride (ChCl). The preparation routes ꢁor DESs are shown in
Scheme1. And it was used as the catalyst ꢁor the ꢀrst time in the improved Skraup
reaction aimed to the synthesis oꢁ 1,10-phenanthroline with a higher yield and
mild reaction conditions. The catalytic perꢁormances oꢁ DESs in the synthesis
oꢁ 1,10-phenanthroline have been tested. Moreover, the physicochemical proper-
1
ties oꢁ DESs were characterized by Fourier transꢁorm inꢁrared, HNMR, pH/mV
meter and thermogravimetric analysis. Meanwhile, the best catalytically active
catalyst was ꢁound to be DES ꢁormed by choline chloride and sulꢁanilic acid. The
optimum technological conditions were also optimized.
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3

M. Wu et al.
Scheme 1 Synthesis oꢁ DESs
Experimental section
Materials
8
-Aminoquinoline (98%) and acrolein (95%) were purchased ꢁrom Jiangsu Aikon
Biopharmaceutical R&D Co., Ltd. 1,10-phenanthroline (>99%) was purchased
rom Sinopharm Chemical Reagent Co., Ltd. Sulꢁamic acid (AR) and choline
ꢁ
chloride (AR) were purchased ꢁrom Shanghai Macklin Biochemical Co., Ltd.
Aminomethane sulꢁonic acid (98%) was purchased ꢁrom Shanghai Meryer Chem-
ical Technology Co., Ltd. Sulꢁanilic acid (99.5%) was purchased Shanghai Tengz-
hun Biotechnology Co., Ltd. Sulꢁuric acid (98%) and p-toluenesulꢁonic acid (AR)
were obtained ꢁrom Chengdu Kelong Chemical Co., LTD, China. All the Metha-
nol, Ethanol, Acetonitrile, N,N-Dimethylꢁormamide and Dimethyl sulꢁoxide were
A.R. grade reagents and were purchased ꢁrom Guangdong Guanghua Sci-Tech
Co., Ltd. All the reagents were used as received without ꢁurther puriꢀcation.
Deep eutectic solvents preparation
The preparation method oꢁ deep eutectic solvents was by heating the mixture oꢁ
choline chloride and hydrogen bond donor. In a typical process, choline chloride
(
ChCl) with HBD in the speciꢀed molar ratio was mixed. The deep eutectic sol-
vents were obtained by mixing the two components and heated in an oil bath until
a colorless homogeneous liquid was simply ꢁormed. Then, the DES was dried in a
vacuum drying oven at about 70 °C ꢁor 4 h, which was then stored in a desiccator
ꢁor ꢁurther use.
1
3

Deep eutectic solvents used as catalysts for synthesis of…
Characterizations of deep eutectic solvents
The DESs were characterized by Fourier transꢁorm inꢁrared (FT-IR) spectra were
−1
obtained with Thermo Fisher Nicolet 670 in the wavelength range oꢁ 4000 cm to 500
−
1
−1
1
cm and the resolution was 4 cm , using KBr powders. H nuclear magnetic reso-
nance (NMR) spectra were carried out on a Bruker Avance Neo 600 MHz type spec-
trometer at room temperature (600 MHz) and TMS as internal standard in DMSO. The
acidity oꢁ DESs in organic solvent solution was investigated at a certain concentration
oꢁ 0.025 g/mL, which was tested by the PHS-3C type pH/mV meter. Thermogravimet-
ric analysis (TGA) was perꢁormed on a SDT Q600 V20.9 Build 20 thermal analyzer on
−1
−1
the conditions oꢁ a heating rate oꢁ 5 °C min , a nitrogen gas ꢃow oꢁ 30 mL min , over
the 30–750 °C temperature range.
The synthesis and analysis of 1,10‑phenanthroline
Generally, the experiment was carried out in a 100 mL three-necked ꢃask with a ther-
mometer, a condensing tube and a gas absorption device oꢁ sodium hydroxide solu-
tion. In a typical reaction process, a certain amount oꢁ 8-aminoquinoline and DES cata-
lyst and solvent were placed into the ꢃask and allowed to melt at a certain temperature
under magnetic agitation. When the reaction mixture was quickly heated to designed
temperature, the acrolein was added into the ꢃask, too. Aꢁter reaction, the reaction
products were cooled to room temperature ꢁor ꢁurther analysis. A high-perꢁormance
liquid chromatography (HPLC, Waters e2695) equipped with a 2414 reꢁractive index
(
RI) detector and Asahipak column (NH P-50 4E, No. N1670026) was used to analysis
2
the products. Methanol/water/Triethylamine (0.65:0.35:0.0005) mixture was used as an
eluent ꢁor the analysis with the ꢃow rate oꢁ 1 mL/min. The temperature oꢁ RI detector
was maintained at 40 °C throughout the analysis. The temperature oꢁ RI detector was
maintained at 40 °C throughout the analysis. Conversion oꢁ 8-aminoquinoline (Con.)
and 1,10-phenanthroline selectivity (Sel.) was deꢀned according to the ꢁollowing equa-
tions. (1–3):
moles of reacted 8 − a min oquinoline
Con.%
∗ 100
(1)
moles of initial 8 − a min oquinoline
moles of producted 1, 10 − phenanthroline
moles of reacted 8 − a min oquinoline
Sel.% =
∗ 100
(2)
(3)
Yield.% = Con. ∗ Sel. 100%
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M. Wu et al.
Results and discussions
Screening of DESs catalysts
The catalytic activity oꢁ DESs with diferent molar ration oꢁ hydrogen bond accep-
tor (HBA) and hydrogen bond donor (HBD) in the synthesis oꢁ 1,10-phenanthroline
ꢁ
rom acrolein and 8-amionquionline has been investigated. The result is shown in
Table 1. It is demonstrated that the yield oꢁ 1,10-phenanthroline ꢁollows the trend oꢁ
SFA>SMA>ASA when the HBD is not the same one. Furthermore, it also can be
seen when the HBD as the same, the yield ꢁollows as the HBD: HBA molar ration oꢁ
1
:2 is the best one. Thus, the HBD: HBA molar ration oꢁ 1:2 DESs system ꢁormed
by sulꢁamic acid, aminomethane sulꢁonic acid and sulꢁanilic acid with choline chlo-
ride were named DES1, DES2 and DES3, respectively, which were selected ꢁor the
synthesis oꢁ 1,10-phenanthroline, and the reaction conditions were ꢁurther explored.
The ratios oꢁ 1:1,1:2, and 2:1 are reꢁer to the molar ration oꢁ two compounds.
SMA: sulꢁamic acid, ASA: aminomethane sulꢁonic acid, SFA: sulꢁanilic acid.
FT‑IR spectra analysis of DESs
To conꢀrm whether the DESs were synthesized, the sulꢁamic acid, aminometh-
ane sulꢁonic, sulꢁanilic acid and DESs were characterized by FT-IR as shown in
Fig. 1. As observed in Fig. 1a, the characteristic peak appeared at around 3158
−
1
−1
cm and 3412 cm were belonged to asymmetrical stretching vibration oꢁ N–H
−
1
oꢁ sulꢁamic acid and the 2455 cm was the stretching vibration oꢁ -NH . In con-
2
trast, with the addition oꢁ choline chloride, the absorption peak at around 2455
−
1
−1
cm oꢁ DES1 was disappeared, and the absorption peaks oꢁ 3158 cm and
−
1
−1
−1
3
412 cm blue-shiꢁted to 3208 cm and 3416 cm with an enhanced absorp-
tion band. It may be caused by hydrogen bonds ꢁormed through the interaction oꢁ
materials [19]. Similarly, as illustrated in Fig. 1b, the characteristic absorption
−
1
−1
peaks at around 754 cm and 1606 cm were attributed to the out-oꢁ-plane wag-
ging vibration oꢁ N–H and scissoring vibration oꢁ −NH . The addition oꢁ choline
2
Table 1 The catalytic
Number Cat(10wt%) Ration Con (%) Sel (%) Yield (%)
a
perꢁormance oꢁ diferent DESs
1
2
3
4
5
6
7
8
9
SMA/Chcl
SMA/Chcl
SMA/Chcl
ASA/Chcl
ASA/Chcl
ASA/Chcl
SFA/Chcl
SFA/Chcl
SFA/Chcl
1/1
1/2
2/1
1/1
1/2
2/1
1/1
1/2
2/1
76.8
70.0
68.0
58.5
63.5
56.5
76.3
71.9
72.3
57.9
66.0
59.2
52.6
62.3
60.2
70.1
84.1
72.1
44.5
46.2
40.3
30.8
39.6
34.0
53.5
60.5
52.1
a
Reaction conditions: V(DMF)=10 mL, n(8-AQ)=1 mmol,
n(Acrolein)=1.5 mmol, cat=10wt% oꢁ 8-AQ, T=130 ℃ t=4 h
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3

Deep eutectic solvents used as catalysts for synthesis of…
Fig. 1 FT-IR spectra oꢁ sulꢁamic acids (a), aminomethane sulꢁonic (b), sulꢁanilic acid (c) and DESs
chloride reduced the absorption intensity oꢁ the out-oꢁ-plane wagging vibration oꢁ
−
1
N–H and the peak oꢁ scissoring vibration oꢁ −NH was moved to 1610 cm . Fur-
2
−
1
thermore, the stretching vibration absorption peaks oꢁ N–H at around 3419 cm
−
1
and 3445 cm were signiꢀcantly enhanced, which could correspond to the ꢁor-
mation oꢁ a large number oꢁ hydrogen bonds [20]. In Fig. 1c, there was no signiꢀ-
cant shiꢁt in the absorption peaks oꢁ the out-oꢁ-plane wagging vibration oꢁ N–H
−
1
−1
at 836 and 832 cm and the stretching vibration oꢁ C-N at 1246 cm , which
is consistent with the results reported by literature [19]. However, in the band
−
1
ꢁ
rom 2500 to 3000 cm , the absorption peaks oꢁ hydroxyl groups on the sulꢁonic
acid groups were weakened. In the meantime, the strength oꢁ the absorption band
−
1
at 3429 cm was signiꢀcantly increased, which would ꢁurther be conducive to
show that hydrogen bonds were ꢁormed between choline chloride and sulꢁanilic
acid [21].
In addition, the asymmetrical stretching vibration oꢁ the terminal methyl group
−
1
oꢁ choline chloride was also observed at the 1479 cm in the FT-IR spectra oꢁ the
+
three DESs suggested that the structure oꢁ Ch was not destroyed, which could ꢁur-
ther be indicated choline chloride and the HBDs were mainly connected by hydro-
gen bonds [22].
1HNMR spectra analysis of DESs
1
The hydrogen bond interaction oꢁ DESs was also investigated by H NMR tech-
nique as shown in Fig. 2. As illustrated in Fig. 2a, the H signal at 12.16 ppm oꢁ
sulꢁamic acids has a higher ꢀeld shiꢁt and moves to 12.04 ppm aꢁter the ꢁormation
oꢁ the DES. Similarly, the H signal at 6.03 ppm oꢁ aminomethane sulꢁonic also
moves to 5.92 ppm as shown in Fig. 2c. In addition, we ꢁound that the H signal at
1
2.09 ppm oꢁ -OH oꢁ sulꢁanilic acid has a lower ꢀeld shiꢁt moves to 12.61 ppm in
Fig. 2e, which may because oꢁ the deshielding and steric efects oꢁ benzene ring.
These results prove the ꢁormation oꢁ hydrogen bonds between the HBA and HBD
[
22] [23]. Besides, the chemical shiꢁt oꢁ H signal in choline chloride has no obvious
chemical shiꢁt beꢁore and aꢁter the ꢁormation oꢁ DESs, which would be conducive to
show that the structure oꢁ choline chloride did not change signiꢀcantly. The results
were consistent with the results oꢁ FT-IR analysis.
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3

M. Wu et al.
Fig. 2 1H NMR spectra oꢁ sulꢁamic acids and DESs and corresponding enlarged image
Acidity of DESs in N,N‑dimethylformamide (DMF) and Dimethyl sulfoxide (DMSO)
It is a matter oꢁ great concern to ꢁocus on the acidity ꢁor DESs as the acidic
catalyst, and there are many researches which expound the acidity oꢁ DESs by
1
3

Deep eutectic solvents used as catalysts for synthesis of…
perꢁorming pH measurements [24]. So, in order to explore the acidity oꢁ three
DESs under the reaction conditions, the inꢃuence oꢁ temperature on the pH value
oꢁ DESs at a concentration oꢁ 0.025 g/mL with DMF and DMSO as the organic
solvent were investigated as shown in Fig. 3. According to Fig. 3a, temperature
has a remarkable efect on acidity and the pH value oꢁ DESs can be ordered as
ꢁ
ollows: DES2 > DES1 > DES3. Meanwhile, when the temperature increased
ꢁ
rom 85 to 145 °C, the pH value oꢁ three DESs were decreased rapidly. However,
the pH value oꢁ DES2 at 160 °C was observed to rise gradually, which could be
+
resulted by the weakened hydrogen bonds or part oꢁ Ch would be just released
[
25] at a higher temperature. Similarly, in Fig. 3b, the pH value trend oꢁ DES in
DMSO is consistent with that in DMF. In addition, the pH value oꢁ the DESs is
dependent upon the hydrogen bond donor.
Thermogravimetric analysis of DESs
To investigate the thermal stability oꢁ DESs, the DESs were studied by TGA
under the protection oꢁ nitrogen as shown in Fig. 4. The DES1 and DES3 showed
prominent thermodynamic stability when the temperature did not exceed about
2
40 °C. The TG curves oꢁ DES1 and DES3 lost 3.76% and 7.77% between 30
and 236 °C, which was in connection with the removal oꢁ physic-adsorbed H O.
2
As the temperature continues to rise, DES1 and DES3 began to decompose and
reached the maximum decomposition rate at 326 and 240 °C, respectively. The
decomposition temperature oꢁ DES2 is lower than DES1 and DES3, however,
which is ꢁurther proved that the pH value increases because oꢁ the release part
+
oꢁ Ch aꢁter the temperature exceeds 145 °C. Thereꢁore, it can be concluded that
DESs can act as stable compounds to catalyze the improved Skraup reaction.
Fig. 3 Efect oꢁ temperature on pH in an organic solvent oꢁ DESs
1
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M. Wu et al.
Fig. 4 TG and DTG curves oꢁ DESs
Evaluation of catalytic performance of DESs
To investigate the catalytic activity oꢁ DESs, 8-aminoquinoline (8-AQ) was dis-
solved in diferent solvents ꢁor exploratory reactions. Unꢁortunately, the target
product oꢁ 1,10-phenanthroline had not been obtained, no matter whether the type
oꢁ catalysts, the amount oꢁ catalysts, the reaction temperature, and the reaction
time were changed when in the protic solvent such as methanol or ethanol solu-
tions. The reason is may that the hydrogen bond system oꢁ DESs was destroyed in
protic solvents, thus losing its catalytic activity. Subsequently, the efects oꢁ DESs
catalyze 8-AQ and acrolein ꢁor the synthesis oꢁ 1,10-phenanthroline by improved
Skraup reaction in the aprotic solvents DMF and dimethyl sulꢁoxide (DMSO)
were investigated. The results are listed in Table 2.
When a single component was used as a catalyst to catalyze the reaction, the
conversion and selectivity oꢁ the sulꢁamic acid catalyst were the highest, 85.2 and
2
9.5%, respectively. In the meanwhile, it can be seen that it was ꢁailure to obtain
the target product when choline chloride was used as a catalyst. But the difer-
ence is the catalytic perꢁormance oꢁ three DESs showed good catalytic efect
and DES3 exhibits the best catalytic efect, with 71.9% conversion rate, which
is much better than the DES1(70.0%) and DES2(68.5%). It can be seen that the
stronger the acidity oꢁ DESs, the highest catalytic activity. Otherwise, the cata-
lytic acidity oꢁ all the DESs is much better than the single component, which
would be conducive to show that the choline chloride has interacted the HBDs.
However, although DES3 has the best catalytic activity in DMSO solvent com-
pared with the DES1 and DES2, it is lower than in the DMF solvent. This is
mainly because DMSO decomposed into ꢁormaldehyde [26] when heated under
acidic condition and ꢁormaldehyde reacts with the amino group on 8-aminopu-
inoline to ꢁorm Schif base [27] and other by-products. So, DES3 and DMF were
selected as the best catalyst and reaction solvent ꢁor the investigation and optimi-
zation oꢁ the next process conditions.
1
3

Deep eutectic solvents used as catalysts for synthesis of…
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3

M. Wu et al.
Inꢀuence of reaction conditions on reaction results
A large amount oꢁ by-products might be ꢁormed in the process oꢁ 8-AQ and acr-
olein to 1,10-phenanthroline with diferent reaction conditions. Thus, the inꢃu-
ence oꢁ reaction parameters such as reaction temperature, the amount oꢁ catalysts,
the molar ratio oꢁ material and reaction time on the reactions was investigated
to achieve high yield, as exhibited in Fig. 5. As an important reagent ꢁor cycli-
zation, acrolein is considered to have a low boiling point and is prone to selꢁ-
polymerization under the inꢃuence oꢁ temperature [28]. Thereꢁore, the efect oꢁ
reaction temperature on the reaction perꢁormance was ꢀrst studied, and the results
are shown in Fig. 5a. As the temperature increases, the conversion oꢁ 8-aminoqui-
noline gradually decreases, while the yield and selectivity oꢁ 1,10-phenanthroline
show a tendency to increase ꢀrst and then decrease, which is caused by the selꢁ-
polymerization oꢁ acrolein at higher temperature and some side reactions. The
highest yield 60.5% can be obtained at 130 °C with the conversion are 71.9%.
Hence, 130 °C was to be selected the optimal reaction temperature.
Fig. 5 Efect oꢁ diferent reaction conditions on reaction perꢁormance: (a) Reaction temperature
(
acrolein:8-aminoqulinoline (1.5:1), cat(10wt%),4 h), (b) The amount oꢁ catalyst (acrolein:8-aminoqulin-
oline (1.5:1),130 ℃, 4 h), (c) Molar ration oꢁ acrolein to 8-amionqulinoline (130 ℃, cat(10wt%), 4 h), (d)
Reaction time (acrolein:8-aminoqulinoline (2:1),130 ℃, cat(10wt%)
1
3

Deep eutectic solvents used as catalysts for synthesis of…
The efect oꢁ the amount oꢁ DES3 on the reaction is shown in Fig. 5b. When
the amount oꢁ DES3 is 4 wt% oꢁ 8-aminoquionline, the 8-aminoquinoline conver-
sion rate and product yield are 52.0% and 30.1%, respectively. When the amount oꢁ
DES3 is continuously increased, the conversion and selectivity are also increased.
The highest target product yield 60.5% and selectivity 84.1% can be obtained with
the amount oꢁ 10wt% oꢁ catalyst. However, when the amount oꢁ the catalyst exceeds
1
0wt%, the selectivity is reduced. It may be because the excessive amount oꢁ cata-
lyst accelerates the occurrence oꢁ some side reactions. Thereꢁore, the optimal cata-
lyst dosage oꢁ 10 wt% was selected ꢁor ꢁurther study.
The inꢃuence oꢁ the molar ratio oꢁ acrolein to 8-aminoquinoline on the reaction
was also investigated. As shown ꢁrom Fig. 5(c), with the increase in the amount oꢁ
acrolein, the conversion oꢁ 8-AQ and the yield oꢁ 1,10-phenanthroline increased to
8
9.3% and 75.6% by the molar ratio to 2:1. Aꢁter that, increasing the amount oꢁ acr-
olein did not signiꢀcantly improve the product yield. It may be because acrolein had
a relatively high concentration in the reaction system and a part oꢁ itselꢁ polymer-
izes, so that too much acrolein did not participate in the actual reaction process [29].
Finally, efect oꢁ reaction time on the conversion oꢁ 8-AQ and the yield oꢁ 1,10-phen-
anthroline was investigated at time oꢁ 1, 2, 3, 4, and 5 h. As seen in Fig. 5d, when
the reaction time extend ꢁrom 1 to 4 h, the 1,10-phenanthroline yield increased ꢁrom
5
8.6 to 75.6%. Further prolongating it to 5 h, the 1,10-phenanthroline yield was
not signiꢀcantly enhanced. Thereꢁore, 4 h was considered to be the optimal reac-
tion time. Based on the analysis oꢁ the actual experimental results above, the opti-
mal conditions ꢁor synthesis oꢁ 1,10-phenanthroline by improved Skraup reaction
were temperature 130 °C, molar ratio oꢁ acrolein to 8-aminoquinoline ratio 2:1, DES
amount 10 wt% oꢁ the mass oꢁ 8-AQ and time 4 h. Under the optimal reaction con-
ditions, the yield oꢁ the product can reach 75.6%,which was similarly reported in
literature [12].
To assessment the catalytic properties oꢁ DES, some results oꢁ synthesis oꢁ
1
,10-phenanthroline using diferent methods are summarized in Table 3. In most
oꢁ the studies, lower yield oꢁ 1,10-phenanthroline was obtained and high catalyst
amounts. Otherwise, some oꢁ the reagents and catalysts were expensive. In this
study, it was reported that the 75.6% yield oꢁ 1,10-phenanthroline was obtained
using DES as the new catalyst ꢁrom acrolein and 8-aminoquinoline. Moreover, under
the optimal reaction conditions, we used sulꢁuric acid and p-toluenesulꢁonic acid to
replace oꢁ DES as catalysts ꢁor comparison, only the yield oꢁ 9 and 20%, respec-
tively. So, it is remarkable when compared to conventional catalysts. Unꢁortunately,
we were unable to successꢁully isolate the catalyst ꢁrom the reaction system because
the DESs were completely dissolved in the solution.
Plausible reaction pathway
Based on the research, a possible mechanism ꢁor synthesis oꢁ 1,10-phenanthroline
ꢁ
rom acrolein and 8-aminoquinoline in the presence oꢁ the DES catalyst is proposed
in Scheme 2. The regioselective 1,4-
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M. Wu et al.
Table 3 Comparison oꢁ results with other studies. a: Yield by GC-area, b: Yield by HPLC, the others are
isolated yield
Number Solvent Reagent A
Reagent B
Catalyst
Au-
Yield (%) Reꢁ
1
75a
[12]
NP@Al O
2
3
2
3
DMF
EtOH
Cu
67
47
[11]
[30]
KOH
4
CH CN
Zn(OTꢁ)2
Pd-NPs
68
[10]
3
5
6
H O
78
15
[31]
[6]
2
H O
H SO4
2
2
7
8
H O
H SO4
45
[32]
2
2
DMF
DES
75.6b
This study
addition oꢁ 8-aminoquinoline to acrolein aforded the corresponding aldehyde 1,
and subsequent generate 3 via the process oꢁ cyclization and dehydration. Finally,
the 3 oxidative aromatization would then provide the product 1,10-phenanthroline 4.
1
3

Deep eutectic solvents used as catalysts for synthesis of…
Scheme 2 The plausible reaction pathway to ꢁorm quinoline ꢁrom 8-aminoquinoline and acrolein
Alternatively, it is possible that the ꢁormation oꢁ unsaturated imine 5 ꢀrst through a
condensation reaction. Subsequently, the imine 5 reacts with another 8-aminoquino-
line to ꢁorm double-quinoline-structured imine [33], which converts to 7 via hydrog-
enolysis. Finally, 8-aminoquinoline elimination and oxidative aromatization would
then deliver the product 4.
Conclusions
The use oꢁ acidic deep eutectic solvents as new homogeneous catalysts ꢁor the syn-
thesis oꢁ 1,10-phenanthroline by improved Skraup reaction has been reported ꢁor
the ꢀrst time. Deep eutectic solvents were prepared using choline chloride and sev-
eral sulꢁamic acid, aminomethane sulꢁonic acid and sulꢁanilic acid. On the other
hand, the characterization results show that the ꢁormed DESs are mainly connected
through the hydrogen bond interaction between the hydrogen bond donor and the
hydrogen bond acceptor (choline chloride). The maximum selectivity and yield oꢁ
1
,10-phenanthroline as 84.6% and 75.6% were achieved using DES3 ꢁormed by cho-
line chloride and sulꢁanilic acid, which has the strongest acidity, within temperature
1
30 °C, molar ratio oꢁ acrolein to 8-aminoquinoline ratio 2:1, DES amount 10 wt%
oꢁ the mass oꢁ 8-aminoquinoline and time 4 h. Moreover, the DESs system will be
viewed as a new system ꢁor improved Skraup reaction oꢁ 8-aminoquinoline with acr-
olein and this result may provide a novel thought ꢁor other possible synthesis and
applications oꢁ nitrogen-containing heterocyclic compounds.
1
3

M. Wu et al.
Acknowledgements We are thankꢁul ꢁor the ꢀnancial support provided by Sichuan Province Regional
Innovation Cooperation(2020YFQ0003). The authors also would like to thank Pan Li ꢁrom Shiyanjia Lab
1
(
www.shiyanjia.com) ꢁor the FR-IR, HMR and TGA tests.
Declarations
Conꢀicts of interest There are no conꢃicts to declare.
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1
3

Deep eutectic solvents used as catalysts for synthesis of…
Authors and Aꢀliations
Mingliang Wu1,2 · Yuansheng Bai · Xuejun Chen · Qingyin Wang ·
1
1
1
Gongying Wang1
,2
*
Gongying Wang
wanggongying1102@126.com
1
2
Chengdu Institute oꢁ Organic Chemistry, Chinese Academy oꢁ Sciences, Chengdu 610041,
Sichuan, China
National Engineering Laboratory ꢁor VOCs Pollution Control Material & Technology,
University oꢁ Chinese Academy oꢁ Sciences, 19A Yuquan Road, Shijingshan District,
Beijing 100049, China
1
3