NbCl5 a multifunctional reagent for the synthesis of new halogenated aminoquinoline compounds through innovative one-pot reaction and the acidochromism effect

Article abstract of DOI:10.1016/j.tet.2018.09.003

This paper describes an original one-pot way to synthesize nine new halogenated aminoquinoline derivatives using reactions conducted by niobium pentachloride. Subsequently, we describe an efficient and selective reduction reaction of nitroquinolines using niobium pentachloride and zinc, producing important compounds in the organic synthesis. The results showed that it is an important tool to synthesize these compounds, besides being time- and resources-saving and generating good yields. A quick study of acidochromism was performed.

Full text of DOI:10.1016/j.tet.2018.09.003

Accepted Manuscript
NbCl a multifunctional reagent for the synthesis of new halogenated aminoquinoline
5
compounds through innovative one-pot reaction and the acidochromism effect
Giovanny Carvalho dos Santos, Vitor Fernandes Moreno, Paula Beatriz Oshiro, Luiz
Carlos da Silva-Filho
PII:
S0040-4020(18)31056-1
10.1016/j.tet.2018.09.003
TET 29775
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 20 August 2018
Revised Date: 30 August 2018
Accepted Date: 2 September 2018
Please cite this article as: dos Santos GC, Moreno VF, Oshiro PB, da Silva-Filho LC, NbCl a
5
multifunctional reagent for the synthesis of new halogenated aminoquinoline compounds through
innovative one-pot reaction and the acidochromism effect, Tetrahedron (2018), doi: 10.1016/
j.tet.2018.09.003.
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ACCEPTED MANUSCRIPT
NbCl5 a multifunctional reagent for the synthesis of new halogenated
aminoquinoline compounds through innovative One-pot reaction and the
acidochromism effect.
Giovanny Carvalho dos Santos, Vitor Fernandes Moreno, Paula Beatriz Oshiro and Luiz Carlos da
Silva-Filho*
Laboratory of Organic Synthesis and Processes (LOSP), São Paulo State University (UNESP),
Department of Chemistry, School of Sciences, 17033-360, Bauru, São Paulo, Brazil
Fax +55(14) 31036099:*e-mail: lcsilva@fc.unesp.br
Abstract: This paper describes an original one-pot way
to synthesize nine new halogenated aminoquinoline
derivatives using reactions conducted by niobium
pentachloride. Subsequently, we describe an efficient
and selective reduction reaction of nitroquinolines using
niobium pentachloride and zinc, producing important
compounds in the organic synthesis.
The results showed that it is
an important tool to
synthesize
these
compounds, besides being
time- and resources-saving
and generating good yields.
A
quick
study
of
acidochromism
performed.
was
Keywords: Niobium Pentachloride, One-Pot Reactions, Aminoquinoline Derivatives, Selective
Reduction Reactions.
1

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1. Introduction
The growing interest in niobium compounds for organic synthesis and catalysis is highlighted by
the commercially available niobium pentachloride (NbCl5), which is highly electrophilic, making it
possible to act as a Lewis acid [1]. Among the recent applications of NbCl5 in the organic synthesis and
catalysis, there are: synthesis of β-mercapto compounds, 3,4-dihydropyrimidinones (Biginelli reaction),
1,3-dicarbonyl compounds with amines condensation and β-keto esters, catalysis and promotion of
Friedel-Crafts acylation, acetylation of alcohols and phenols, Mannich-type reactions, Knoevenagel
condensation, aldol and aza-aldolic reactions, Sakurai reaction, cross-coupling reactions, carbonyl
compounds coupling reactions, reduction reactions, cycloaddition and cyclization, multicomponent
reactions, one-pot and polymerization reactions, and also transesterification/esterification of microalgae
to biodiesel production, Diels-Alder reactions, among others [2-4]. Furthermore, in the last years, NbCl5
has been used by our group and has proven to be an efficient and versatile catalyst in synthetic
methodologies in several reactions to synthesize important compounds: isoquinuclidine, xanthenedione,
4H-pyran, fluorescein, methoxylated phloroglucinol, chromeno[4,3-b]chromene, quinoline, xanthene and
tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives [5].
One type of these important compounds is the quinoline derivatives, which are important N-
based heterocyclic compounds that are characterized by a benzene ring fused to a pyridine ring. These
molecules have been an important subject to numerous research groups. Several authors highlight the
importance of quinoline derivatives for having many biological applications against several diseases and
for its use in polymer chemistry, organic electronics and optoelectronics [6]. Among these uses, the
authors also mention the manufacturing of dyes, food colorants, pH indicators and their use as corrosion
inhibitors [6].
With this great potential of applicability for the quinoline derivatives, research groups have
invested in the synthesis of this heterocyclic compound. Our research group has recently described the
synthesis of aminoquinoline derivatives (two-steps) through multicomponent reaction (MCR) catalyzed
by Niobium Pentachloride, followed by a reduction of the nitro group with Pd/C and hydrazine [7]. But
this method shows a Pd-catalyzed hydrogenolysis of compounds with carbon-halogen bonds with
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hydrazine as a hydrogen donor. In the literature we know about several methods to reduce nitro
compounds to their respective amines, but many of them are not selective to any group [8].
Bearing this in mind, this study has shown that the conversion of halogenated nitroquinolines
with fluorides, bromides and chlorides into their corresponding aminoquinolines is possible, based on a
report of Yoo and co-workers [9] that described the use of the NbCl5/In system as a reagent for the
chemoselective reduction of aromatic nitrocompounds [9]. Here we use zinc instead of indium to reduce
the production cost of the final molecule. In addition, we describe a new method for directly obtaining
unpublished halogenated aminoquinoline derivatives in a one-pot reaction using the NbCl5/Zn system.
2. Results and discussion
2.1. Two steps synthesis of aminoquinoline derivatives.
In a recent work, we studied the synthesis of nitroquinoline derivatives by MCRs using NbCl5 as
promoter, showing good yields for the production of the nitroquinoline derivative, regardless of the
benzaldehyde derivatives used [7]. The MCRs were conducted between p-nitroaniline (1) (1.0 eq.),
benzaldehyde derivatives (2a-j) (1.0 eq.) and phenylacetylene (3) (1.0 eq.) under air atmosphere, room
temperature, constant stirring and using anhydrous acetonitrile (CH3CN) as solvent. NbCl5 was used in
the proportion of 50% for each mol of benzaldehyde derivative used. The reduction of the nitro group in
the nitroquinoline derivatives was conducted with hydrazine monohydrate in the presence of 10% Pd/C
(Procedure 1), but these reaction conditions resulted in the dehalogenation of the products, obtaining
only the compound 5a as product [7]. In this present work, we decided to test the NbCl5/Zinc system in
the reduction of the nitro group (Procedure 2). Procedure 2 is selective and the halogen bond (-Br, -Cl
and –F) with aromatic ring remained unaffected. This method shows that it is possible to obtain new
aminoquinoline with its halogen substituent. The reduction of the nitro group in all nitroquinoline
derivatives (5a-j) was successfully obtained and presented reasonable yields without the removal of the
halogen (Scheme 1).
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Scheme 1 Synthesis of aminoquinolines 5a-j in two ways
The results are summarized in Table 1 and show the difference of yields between the
procedures.
Table 1 Benzaldehyde derivatives used and reaction yields
Aldehyde R1 R2 R3 R4 R5 Aminoquinoline Yield(%)a,b Aminoquinoline Yield (%)a,c
H
F
H
H
H
H
F
H
H
H
H
H
H
H
F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
92 (5a)
63 (5a)
2a
2b
2c
2d
2e
2f
91 (5a) and 0 (5b)
94 (5a) and 0 (5c)
93 (5a) and 0 (5d)
84 (5a) and 0 (5e)
92 (5a) and 0 (5f)
90 (5a) and 0 (5f)
84 (5a) and 0 (5h)
80 (5a) and 0 (5i)
87 (5a) and 0 (5j)
67 (only 5b)
69 (only 5c)
68 (only 5d)
61 (only 5e)
53 (only 5f)
51 (only 5g)
62 (only 5h)
46 (only 5i)
32 (only 5j)
Cl
Br
H
H
H
H
H
H
Cl
Br
H
H
H
2g
2h
2i
Cl
Br
2j
aYields of isolated products after recrystallization
bMethod with Pd/C and hydrazine
cMethod with NbCl5 and zinc
Although the yields were not very good when the reduction method with the NbCl5/Zn system
was used, we were able to observe the formation of the respective aminoquinoline derivatives (5b-j)
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containing the halogens while, when the Pd/C system was used, only the formation of aminoquinoline 5a
was verified, independent of the nitroquinoline derivative used, probably due to its reductive reactional
condition, which also resulted in the dehalogenation of the products. In general, higher yields were
observed when the halogens were in the ortho position, followed by meta position and finally the para
position. With some exceptions, in the general behavior regarding which halogen was used, we have the
best yields with F, Cl and Br, respectively. These results can be explained by the bond strength of the
halogens [10].
The reduction process of the nitroquinoline derivatives occurs by the generation of low-valent
niobium complexes, formed from the reduction of NbCl5 by using zinc metal. Previous experiments
showed us that NbCl5 or Zn separately do not initiate the reaction [9]. Therefore, we need the formation
of a NbCl5/Zn system in order to reduce the nitro group, which occurs by the reductive cleavage of
polarized N-O bonds that are polarized by a single electron transfer (SET) process.
The chemical structures of the resulting new halogenated aminoquinoline derivatives were
1
confirmed by H NMR, 13C NMR, IR and HRMS spectra. In order to emphasize the importance of
halogenated quinolines, we highlight that these compounds have become important intermediates in
metal-catalyzed carbon–carbon bond formation to promote the synthesis novel substituted quinoline
derivatives to act as monomers in polymerization reactions and with potential applications in
pharmaceuticals and materials [11]. In addition, the halogenated quinoline shows potent antibacterial
activities against a broad spectrum of pathogenic bacteria, including multidrug-resistant clinical isolates
[12].
2.2. One-pot synthesis of aminoquinoline derivatives.
In order to improve the synthesis of aminoquinoline derivatives, a new method was performed to
directly obtain these compounds by One-pot reaction using NbCl5 in the two steps of the synthesis.
Firstly, the synthesis of the nitroquinoline derivatives (4a-j) was performed in the same reaction
conditions described previously. After 96 hours of reaction, the solution containing the reducing system
(NbCl5/Zn) was added directly to the reaction medium and, after 6 hours, the formation of
aminoquinoline derivatives (5a-j) with excellent yields was verified. The results obtained are described in
Scheme 2 and Table 2.
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Scheme 2 Synthesis of aminoquinolines 5a-j
Table 2 MCR and One-pot reaction yields
Aldehyde R1 R2 R3 R4 R5
Aminoquinoline Yield (%)a
(One-pot reaction)
90 (5a)
Overall Yield of reactions
in two steps (%)
59 (5a)
H
F
H
H
H
H
F
H
H
H
H
H
H
H
F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2ª
2b
2c
2d
2e
2f
92 (5b)
86 (5c)
87 (5d)
92 (5e)
89 (5f)
90 (5g)
93 (5h)
91 (5i)
88 (5j)
58 (5b)
63 (5c)
55 (5d)
45 (5e)
52 (5f)
40 (5g)
60 (5h)
39 (5i)
31 (5j)
Cl
Br
H
H
H
H
H
H
Cl
Br
H
H
H
2g
2h
2i
Cl
Br
2j
aYields of isolated products after chromatography column by one-pot reaction.
The results show us that this is an important methodology to directly produce aminoquinoline
derivatives with good yields for the halogenated aminoquinolines. In the two-step method, the first with
the MCR followed by extraction and isolation of the product, the second using the compound isolated for
the reduction of the nitro group, we observed a reasonable overall yield (see comparison in table 2), in
addition to reducing the time and solvents spent in the extraction process and purification. On the other
hand, using the new one-pot methodology, we observed good yields and time- and resource-saving during
the synthesis. As to the results, the yields of the halogens in para position are, in general, higher than
those in the meta and ortho positions, respectively. Regarding the type of halogen, the fluorine as
substituent presents the best results.
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Due to the several examples of the application of 2,4-disubstituted quinolines, the one-pot
synthesis shows to be an important method due to its simple and low-cost methodology in obtaining these
derivatives. The chemical structures of the resulting halogenated aminoquinoline derivatives were
confirmed by 1H NMR, 13C NMR, IR and HRMS spectra.
2.3. Photophysical Properties
2.3.1. UV-Vis Absorption Properties
In this study, we add different halogens (F, Cl, Br) substituents at ortho, meta and para positions
to examine the effects on absorption. The absorption spectra of ethanolic solutions (5x10−5 mol.L−1) of
aminoquinoline derivatives are depicted in Fig. 1
5a
5b
5c
1
5d
5e
5f
5g
5h
5i
5j
0
300
350
400
450
500
Wavelength (nm)
Figure 1: UV-Vis absorption of halogenated aminoquinoline derivatives (5a–j) in ethanol
As shown in the others papers [12-13], the absorption spectra of the halogenated aminoquinoline
derivatives in ethanol are characterized by strong absorption peaks centered at approximately 300–330
nm and 369–378 nm attributed to π-π* and n-π* transitions. Visually we did not observe many
differences in shape and shift of the spectrum, the greatest differences are in the intensity. The data of
UV-Vis absorption are summarized in Table 3 in 5x10-5 mol. L−1 EtOH solution.
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Table 3:Maximum absorption wavelength (λmax) for halogenated aminoquinoline derivatives
Aldehyde
R1
H
F
R2
H
H
H
H
F
R3
H
H
H
H
H
H
H
F
R4
H
H
H
H
H
H
H
H
H
H
R5
H
H
H
H
H
H
H
H
H
H
λmax(nm) ethanol
375
372
372
369
376
377
378
373
376
376
2a
2b
2c
2d
2e
2f
Cl
Br
H
H
H
H
H
H
Cl
Br
H
H
H
2g
2h
2i
Cl
Br
2j
The difference in shift among the halogenated aminoquinoline derivatives is not very significant.
In spite of this it is possible to observe a tendency between which is the halogen and in which position is
inserted in the ring. In general, the lowest absorption values are observed for the ortho position, in the
sequence we have the para position and finally the meta position presents the largest displacement for the
red region, these work for all the halogens. Bromine substituent has the lowest absorption wavelength
value in the ortho position (5d) and the highest value in the meta position (5g). These new halogen-
containing compounds can be used as important starting materials for the synthesis of more complex
molecules.
2.3.2. Acidochromism effect in UV-Vis Absorption Properties
We have known that these derivatives show a slight solvatocromism (Fig S1 in Support
Information and ref [13]). Here we added HCl to the compound 5a solubilized in ethanol to know the
effect of protonation on the molecule. We have been observed a protonation of nitrogen based
heterocycles in Figure 2 [14]. The addition changed the color of solution from light yellow to orange in
visible light and from blue to orange color in UV light irradiation (365 nm).
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Figure 2: Effect of nitrogen protonation of quinoline backbone
The addition of HCl caused a batochromism (red shift) of 72nm as observed. To this effect is
given the name of positive acidochromism, where a strong transfer of charge is possible, as
mechanistically suggested in Figure 3. The addition of ammonium hydroxide had no change at the
spectra. All the compounds (5a-j) have shown the same behavior in acidic and basic media.
Figure 3: Absorption spectra of compound 5a and mechanism of charge tranfer.
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3. Conclusion
We found a new method for obtaining aminoquinoline compounds using NbCl5 that proved to be
an excellent reagent for one-pot reactions. All the reactions were conducted at low cost, in mild
conditions and with good yields. Here, a quick study of acidochromism was performed and a positive
acidochromism was observed when we added HCl. Considering the unquestionable importance of
quinoline derivatives in different areas, such as the development of pharmaceuticals, dyes, chemical
polymers and in electronic devices, this methodology developed here proves to be important for a fast and
efficient study about these molecules.
4. Experimental section
4.1. General
All reactions were performed under air atmosphere, unless otherwise specified. Acetonitrile was
distilled from calcium hydride. All commercially available reagents were used without further
purification. The NbCl5 used was supplied by Companhia Brasileira de Metalurgia e Mineração
(CBMM). Thin-layer chromatography was performed on 0.2 mm Merck 60F254 silica gel aluminum
sheets, which were visualized with UV-365nm irradiation. Bruker DRX 400 spectrometer was employed
for the NMR spectra (CDCl3 solutions) using tetramethylsilane as internal reference for 1H and CDCl3 as
an internal reference for 13C. A model 4600 Jasco FTIR was used to record IR spectra (KBr pellets).
HRMS analyses were recorded in a micrOTOF (Bruker), with ESI-TOF detector working on positive
mode.
4.2. General Procedure for the synthesis of nitroquinoline derivatives
The complete synthesis and full spectral characterization (NMR, MS, IR and other techniques) of
nitro compounds were reported previously [7].
4.3. Procedure 1 for the synthesis of aminoquinoline derivatives from nitroquinolines
An ethanol suspension (20.0 mL) of nitroquinoline derivative (1.0 mmol) was heated to 50.0 °C
in the presence of 10%Pd/C and 2.00 mL of hydrazine monohydrate was added to this suspension after 30
min. The reaction mixture became clear as the reaction proceeded. It was then kept at reflux for another
12 hours. After the reaction was complete, the mixture was filtered over Celite twice to remove the Pd/C
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catalyst. Ethanol was removed under reduced pressure. The crude product was recrystallized from
isopropanol. Note: the crystals grew slowly [15].
4.4. Procedure 2 for the synthesis of aminoquinoline derivatives from nitroquinolines
Niobium pentachloride (270 mg, 1.0 mmol), zinc powder (460 mg, 4.0 mmol) and THF (3 mL)
were mixed and the resulting mixture was sonicated for 30 min at room temperature. A black solution of
the complex was obtained. A nitroquinoline derivative (0.5 mmol) was added to this solution. The
reaction mixture was stirred for 6h at room temperature. After the reaction was over, as indicated by TLC,
water was added and then the organic extract was obtained with ethyl acetate. The combined organic
extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced
pressure. The crude product was purified by silica gel column chromatography (hexane:ethyl acetate =
2:1) to yield the aminoquinoline derivative [9].
4.5. Procedure for direct synthesis of aminoquinoline (One-pot reaction)
In a solution of NbCl5 (50 mol%) in 7.0 mL of anhydrous acetonitrile, maintained at room
temperature under air atmosphere, we added a solution of p-nitroaniline (1.0 mmol), phenylacetylene (1.0
mmol) and benzaldehyde derivatives (2a-j) (1.0 mmol) in 3.0 mL of anhydrous acetonitrile. The reaction
mixture was quenched with water (3.0 mL) after 96 hours. Separately, niobium pentachloride (270 mg,
1.0 mmol), zinc powder (460 mg, 4.0 mmol) and THF (3 mL) were mixed and the resulting mixture was
sonicated for 30 min at room temperature. A black solution of the complex was obtained. This solution
was added to the reaction flask. The reaction mixture was stirred for 6h at room temperature. After the
reaction was over, as indicated by TLC, water was added and then the organic extract was obtained with
ethyl acetate. The combined organic extract was washed with brine, dried over anhydrous magnesium
sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column
chromatography (hexane:ethyl acetate = 2:1) to yield the aminoquinoline derivative.
1
4.5.1. 6-amino-2,4-diphenylquinoline (5a) [7]: Yellowish-white solid. mp/ºC =148 – 151 °C. H
NMR (400 MHz, CDCl3): δ8.16 (d, J=1.5 Hz, 2H), 8.14 (s, 1H), 7.72 (s, 1H), 7.56 (d, J=4.5 Hz, 4H),
7.44-7.53 (m, 4H), 7.20 (dd, J=8.8, 2.5 Hz, 1H), 6.99 (d, J=2.5 Hz, 1H), 3.94 (s, 2H) ppm;13C NMR (125
MHz, CDCl3): δ 105.7, 116.7, 119.6, 121.4, 127.1, 128.1, 128.5, 128.7, 128.7, 129.4, 131.3, 138.9, 139.9,
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143.9, 144.6, 146.7, 153.4 ppm. IR (neat): νmax= 698, 763, 1031, 1258, 1377, 1550, 1619, 1671, 2857,
2926, 3303, 3438 cm-1;ESI-HRMS:m/z calcd for C21H17N2 [M + H]+: 297.1386; found 297.1388.
4.5.2. 2-(2-fluorophenyl)-6-amine-4-phenylquinoline (5b): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 8.02-8.07 (m, 2H), 7.68 (d, J = 2.5 Hz, 1H), 7.45-7.54 (m, 5H), 7.35-7.37 (m, 1H), 7.24-
7.29 (m, 1H), 7.12-7.17 (m, 2H), 6.98 (d, J = 2.5 Hz, 1H), 3.85 (s, 2H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 161.9, 159.4, 149.9, 146.1, 145.0, 143.9, 138.8, 131.3, 130.2, 129.5, 128.5, 128.1, 127.3,
124.6, 123.0, 121.5, 116.3, 116.0, 105.6 ppm. IR: νmax= 698, 763, 1031, 1258, 1377, 1550, 1619, 1671,
2857, 2926, 3303, 3438 cm-1. ESI-HRMS: m/z calcd for C21H16FN2 [M + H]+: 315.1292; found
315.1294
4.5.3. 2-(2-chlorophenyl)-6-amine-4-phenylquinoline (5c): Brown foam.
1H NMR (CDCl3,
400MHz): δ = 8.13-8.15 (m, 2H), 8.07 (d, J = 9.0 Hz, 1H), 7.71 (s, 1H), 7.51-7.56 (m, 7H), 7.19 (dd, J =
9.0, 2.5 Hz, 1H), 6.99 (d, J = 2.5 Hz, 1H), 3.87 (s, 2H). 13C NMR (125 MHz, CDCl3): δ = 171.1, 153.3,
145.5, 145.1, 143.7, 139.8, 138.7, 132.5, 131.7, 131.3, 130.0, 129.5, 128.5, 128.1, 127.1, 123.2, 121.4,
105.5 ppm. IR: νmax= 698, 771, 835, 1027, 1081, 1220, 1328, 1483, 1589, 3103 cm-1. ESI-HRMS: m/z
calcd for C21H16ClN2 [M + H]+: 331.0996; found 331.0992.
1
4.5.4. 2-(2-bromophenyl)-6-amine-4-phenylquinoline (5d): Brown foam. H RMN (CDCl3, 400
MHz): δ = 8.05 (d, J = 8.8 Hz, 1H); 7,70 (s, 1H); 7.69-7.67 (m, 2H); 7.58–7.44 (m, 6H); 7.29–7.25 (m,
1H); 7.20 (dd, J = 8.8, 2.5 Hz, 1H); 7.05 (d, J = 2.5 Hz, 1H); 3,92 (s, 2H) ppm. 13C RMN (125 MHz,
CDCl3): δ = 105.6, 121.4, 122.1, 123.2, 127.1, 127.6, 128.1, 128.5, 129.5,129.6, 131.3, 131.6, 133.2,
138.6, 141.82, 143.5, 145.1, 145.5, 154.6 ppm. IR: νmax= 698, 763, 830, 956, 1091, 1297, 1492, 1619,
2366, 3045, 3294, 3442 cm-1. ESI-HRMS: m/z calcd for C21H16BrN2 [M + H]+: 375.0491; found
375.0493.
4.5.5. 2-(3-fluororophenyl)-6-amine-4-phenylquinoline (5e): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 7.79 (d, J= 9.0 Hz, 1H), 7.62-7.67 (m, 2H), 7.41 (s, 1H), 7.17-7.30 (m, 6H), 6.83-6.92 (m,
2H), 6.71 (d, J = 2.5 Hz, 1H), 3.67 (s, 2H) ppm. 13C NMR (125 MHz, CDCl3): δ = 164.6, 151.9, 146.9,
145.0, 143.8, 142.4, 138.8, 131.4, 130.2, 129.4, 128.6, 128.2, 127.5, 122.7, 121.7, 119.4, 115.6, 114.2,
105.6 ppm. IR: νmax= 698, 762, 1215, 1374, 1491, 1623, 1736,2364, 2971, 3030, 3307, 3448 cm-1. ESI-
HRMS: m/z calcd for C21H16FN2 [M + H]+: 315.1292; found 315.1273.
4.5.6. 2-(3-chlorophenyl)-6-amine-4-phenylquinoline (5f): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 7.81-7.84 (m, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.39 (s, 1H), 7.18-7.28 (m, 7H), 6.91 (dd, J =
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9.0, 2.5 Hz, 1H), 6.71 (d, J = 2.5 Hz, 1H), 3.66 (s, 2H) ppm. 13C NMR (125 MHz, CDCl3): δ = 152.1,
146.9, 144.9, 143.9, 138.9, 134.8, 131.3, 129.4, 128.9, 128.6, 128.4, 128.2, 127.3, 121.6, 119.2, 105.7
ppm. IR: νmax= 648, 698, 764, 832, 1030, 1296, 1491, 1622, 3206, 3314 cm-1. ESI-HRMS: m/z calcd for
C21H16ClN2 [M + H]+: 331.0996; found 331.0992.
4.5.7. 2-(3-bromophenyl)-6-amine-4-phenylquinoline (5g): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 8.07 (t, J = 1.8 Hz, 1H), 7.77-7.87 (m, 2H), 7.39 (s, 1H), 7.24-7.29 (m, 6H), 7.09 (t, J = 7.8
Hz, 1H), 6.91 (dd, J = 9.0, 2.5 Hz, 1H), 6.71 (d, J = 2.5 Hz, 1H), 3,64 (s, 2H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 151.6, 146.9, 145.1, 143.8, 142.0, 138.8, 131.6, 131.4, 130.3, 130.2, 129.4, 128.6, 128.2,
127.5, 125.6, 123.1, 121.7, 119.3, 105.6 ppm. IR: νmax= 698, 763, 834, 1028, 1295, 1491, 1621, 3211,
3314, 3440 cm-1. ESI-HRMS: m/z calcd for C21H16BrN2 [M + H]+: 375.0491; found 375.0493.
4.5.8. 2-(4-fluorophenyl)-6-amine-4-phenylquinoline (5h): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 7.86-7.89 (m, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.38 (s, 1H), 7.23-7.28 (m, 5H), 6.89-6.94 (m,
3H), 6.71 (d, J = 2.5 Hz, 1H), 3.63 (s, 2H) ppm. 13C NMR (125 MHz, CDCl3): δ = 169.5, 154.0, 153.9,
151.9, 134.4, 134.2, 130.8, 129.4, 129.2, 125.3, 125.1, 125.0, 124.1, 118.9, 94.1 ppm. IR: νmax= 698, 771,
835, 1027, 1081, 1220, 1328, 1483, 1589, 3103 cm-1. ESI-HRMS: m/z calcd for C21H16FN2 [M + H]+:
315.1292; found 315.1293.
4.5.9. 2-(4-chlorophenyl)-6-amine-4-phenylquinoline (5i): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 7.93 (s, 1H), 7.73-7.80 (m, 2H), 7.40 (s, 1H), 7.13-7.28 (m, 7H), 6.9 (dd, J = 9.0, 2.5 Hz,
1H), 6.71 (d, J = 2.5 Hz, 1H), 3.66 (s, 2H) ppm. 13C NMR (125 MHz, CDCl3): δ = 151.6, 148.9, 145.2,
143.8, 141.7, 138.8, 134.8, 134.4, 129.9, 129.4, 128.6, 128.2, 127.3, 125.2, 121.7, 119.3, 105.5 ppm. IR:
νmax= 698, 771, 835, 1027, 1081, 1220, 1328, 1483, 1589, 3103 cm-1. ESI-HRMS: m/z calcd for
C21H16ClN2 [M + H]+: 331.0996; found 331.0991.
4.5.10. 2-(4-bromophenyl)-6-amine-4-phenylquinoline (5j): Brown foam. 1H NMR (CDCl3,
400MHz): δ = 7.78-7.82 (m, 1H), 7.75 (d, J = 2.5 Hz, 1H), 7.39 (s, 1H), 7.34-7.37 (m, 2H), 7.22-7.31 (m,
5H), 7,05 (s, 1H), 6.92 (dd, J = 9.0, 2.5 Hz, 1H), 6.71-6.74 (d, 2.5Hz, 1H), 3.66 (s, 2H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 169.1, 153.2, 153.3, 152.6, 134.6, 131.4, 129.3, 126.6, 126.5, 125.2, 124.5, 124.4,
124.1, 124.0, 91.5 ppm. IR: νmax= 699, 959, 1094, 1253, 1515, 1623, 3329, 3420 cm-1. ESI-HRMS: m/z
calcd for C21H16BrN2 [M + H]+: 375.0491; found 375.0493.
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Ackowledgments
The authors would like to thank Fundação de Amparo à Pesquisa do Estado de São Paulo
(FAPESP) (Procs. 2012/24199-8, 2015/00615-0, 2016/01599-1 and 2018/14506-7), Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq) (Proc. 302753/2015-0) and Pró-Reitoria de
Pesquisa (PROPe-UNESP) for their financial support. We would also like to thank CBMM – Companhia
Brasileira de Mineralogia e Mineração for the NbCl5 samples. We express our special thanks to N. P.
Lopes, J. N. Mendonça and J. C. Tomaz at the University of São Paulo in Ribeirão Preto for the HRMS
analyses.
Appendix A. Supplementary data
Supplementary data related to this article can be found at XXX
References
[1] B.H. Arpini, A.A. Bartolomeu, C.K.Z. Andrade, L.C. da Silva-Filho, V. Lacerda Jr, Curr. Org. Chem.
12 (2015) 570.
[2] a) C.K.Z. Andrade, R.O. Rocha, Mini-Rev. Org. Chem. 3 (2006) 271. b) C.K.Z. Andrade, Curr. Org.
Synth. 1 (2004) 333.
[3] V. Lacerda Jr., D.A. dos Santos, L.C. Silva-Filho, S.J. Greco, R.B. dos Santos, Aldrichim. Acta 45
(2012) 19.
[4] a) L.C. da Silva-Filho, M.G. Constantino, V. Lacerda Jr., G.V.J. da Silva, Lett. Org. Chem. 1 (2004)
360. b) L.C. da Silva-Filho, M.G. Constantino, A. Cunha Neto, V.C.G. Heleno, G.V.J. da Silva, J.L.C.
Lopes, Spectrochim. Acta A 61 (2004) 171. c) L.C. da Silva-Filho, M.G. Constantino, V. Lacerda Jr.,
G.V.J. da Silva, P.R. Invernize, Beil. J. Org. Chem. 1 (2005) 14. d) L.C. da Silva-Filho, M.G.
Constantino, V. Lacerda Jr., G.V.J. da Silva, P.R. Invernize, Synth. Comm. 37 (2007) 3529. e) L.C. da
Silva-Filho, M.G. Constantino, V. Lacerda Jr., G.V.J. da Silva, Synthesis 16 (2008) 2527. f) L.C. da
Silva-Filho, M.G. Constantino, E.C. Polo, G.V.J. da Silva, Quim. Nova 31 (2008) 763. g) L.C. da Silva-
Filho, M. Frenhe, Orbital 3 (2011) 1.
[5] a) L.M. Martins, S.F. Vieira, G.B. Baldacim, B.A. Bregadiolli, J.C. Caraschi, A. Batagin-Neto, L.C.
da Silva-Filho, Dyes Pigm. 148 (2018) 81. b) W.H. Santos, E.F. Oliveira, F.C. Lavarda, I.A. Leonarczyk,
M.A.B. Ferreira, L.C. da Silva-Filho, L. C. Synthesis 49 (2017) 2402. c) B.H.S.T. Silva, N.L. Marana,
A.C. Mafud, L.C. da Silva-Filho, Struct. Chem. 25 (2014) 327. d) A.A Bartolomeu, M.L. Menezes, L.C.
da Silva-Filho, Synth. Commun. 45 (2015) 1114. e) A.A. Bartolomeu, M.L. Menezes, L.C. da Silva-
Filho, Chem. Pap. 68 (2014) 1593. f) M.S. Siqueira, L.C. da Silva-Filho, Tetrahedron Lett. 57 (2016)
5050. g) B.H.S.T. Silva, B.A. Bregadiolli, C.F.O. Graeff, L.C. da Silva Filho, ChemPlusChem 82 (2017)
261. h) W.H. Santos, L.C. da Silva-Filho, Tetrahedron Lett. 58 (2017) 894. i) P.B. Oshiro, P.S.S.G. Lima,
M.L. Menezes, L.C. da Silva-Filho, Tetrahedron Lett. 56 (2015) 4476.
[6] S. Naidoo, V. Jeena, V. Synthesis 49 (2017) 2621.
14

ACCEPTED MANUSCRIPT
[7] G.C. Santos, A.A. Bartolomeu, V.F. Ximenes, L.C. da Silva-Filho, J. Fluorescence 27 (2017) 271.
[8] A.M. Tafesh, J. Weiguny, Chem. Rev. 96 (1996) 2035.
[9] B.W. Yoo, D.I. Kim, H.M. Kim, S.H. Kang, Bull. Kor. Chem. Soc. 33 (2012) 2851.
[10] D. Behar, P. Neta, J. Phys. Chem. 85 (1981) 690.
[11] a) M.J. Mphahlele, L.G. Lesenyeho, J. Heteroc. Chem. 50 (2013) 1. b) M. Pietrowski, Curr. Org.
Synth. 9 (2012) 470.
[12] a) Y. Abouelhassan, A.T. Garrison, F. Bai, V.M. Norwood, M.T. Nguyen, S. Jin, R.W. Huigens,
ChemMedChem 10 (2015) 1157. b) A. Basak, Y. Abouelhassan, R.W. Huigens III, R. W. Org. Biomol.
Chem. 13 (2015) 10290.
[13] G.C. Santos, R.O. Servilha, E.F. Oliveira, F.C. Lavarda, V.F. Ximenes, L.C. da Silva-Filho, J.
Fluorescence 27 (2017) 1709.
[14] S. Kothavale, N. Sekar, Dyes Pigm 136 (2017) 31.
[15] A.K. Nedeltchev, H. Han, P.K. Bhowmik, Tetrahedron 66 (2010) 9319.
15