Simultaneous regioselective synthesis of trifluoromethyl-containing 1,7-phenanthrolines and quinolines form cyclocondensation reaction of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines

Article abstract of DOI:10.1590/S0103-50532011000800005

This paper reports interesting results of the conventional synthesis of a new series of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40percent yields, form cyclization reactions of N,N′- bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C₆H ₄-(NHCR=CHC(O)CF₃)₂] in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7- aminoquinolines, in 20-73percent yields, simultaneously. The enaminone precursors were obtained form the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF ₃C(O)CH=C(R)OR¹, where R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO₂Ph, 2-furyl and R¹ = Me, Et] with 1,3-phenylenediamine under mild conditions, in 47-91percent yields.

Full text of DOI:10.1590/S0103-50532011000800005

J. Braz. Chem. Soc., Vol. 22, No. 8, 1426-1438, 2011.
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Article
A
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing
1,7-Phenanthrolines and Quinolines from Cyclocondensation Reaction of
N,N’-Bis(oxotrifluoroalkenyl)-1,3-Phenylenediamines
Helio G. Bonacorso,* Rosália Andrighetto, Nícolas Krüger,
Marcos A. P. Martins and Nilo Zanatta
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química,
Universidade Federal de Santa Maria, 97105-900 Santa Maria-RS, Brazil
Este trabalho relata interessantes resultados relativos a síntese convencional de uma nova série
de 2,10-dialquil(aril)-4,8-bis (trifluorometil)-1,7-fenantrolinas, em rendimentos de 22-40%, a
partir das reações de ciclização de N,N’-bis(oxotrifluoralquenil)-1,3-fenilenodiaminas [1,3-C6H4-
(NHCR=CHC(O)CF3)2] em um meio fortemente ácido (PPA) e na ausência de solvente. A rota
sintética também permitiu o isolamento simultâneo de uma nova série de 2-alquil(aril/heteroaril)-
4-trifluormetil-7-aminoquinolinas, em 20-73% de rendimento. As enaminonas precursoras foram
obtidas a partir da reação de 4-alcóxi-1,1,1-triflúor-3-alquen-2-onas [CF3C(O)CH=C(R)OR1, onde
R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furil e R1 = Me, Et] com
1,3-fenilenodiamina em condições brandas, em rendimentos 47-91%.
This paper reports interesting results of the conventional synthesis of a new series of
2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40% yields, from cyclization
reactionsofN,N’-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines[1,3-C6H4-(NHCR=CHC(O)CF3)2]
in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the
isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7-aminoquinolines, in
20-73% yields, simultaneously. The enaminone precursors were obtained from the reaction of
4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF3C(O)CH=C(R)OR1, where R = H, Me, Ph, 4-MePh,
4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl and R1 = Me, Et] with 1,3-phenylenediamine
under mild conditions, in 47-91% yields.
Keywords: enones, enaminoketones, phenanthrolines, quinolines, PPA
CF3
Introduction
Phenanthrolinesarediazaphenanthreneanalogs,polycyclic
aromatic hydrocarbon present in sterols, sex hormones,
cardiac glycosides, bile acids and in the group of morphine
alkaloids.1 Heterocycles containing nitrogen atoms such
1,10-phenanthroline,2 pyronaridine3 andchloroquine-pyrazole
analogs4 are well known for their antimalarial activity. An
example of particular interest of a non-natural antimalarial
agent possessing a trifluoromethyl substituted phenanthrene
skeleton is halofantrine (Figure 1), an effective drug for the
treatmentofmalariawhichpossessesgoodtherapeuticeffects
but some important adverse effects.5 Furthermore, some
angular and linear N-tricyclic similar systems have also been
documented to possess antiviral activity.6
Cl
N(n-Bu)2
Cl
OH
Figure 1. Chemical structure of the non-natural antimalarial halofantrine.
From a synthetic point of view, phenanthrolines
obtained from phenylenediamines are of particular
interest since both outer rings can be constructed
simultaneously.7 However, phenanthrolines can be also
prepared from aminoquinolines.8 The first phenanthroline,
1,7-phenanthroline was prepared by Skraup andVortmann9
in 1882 and the method continues to be one of the best
*e-mail: heliogb@base.ufsm.br

Vol. 22, No. 8, 2011
Bonacorso et al.
1427
methods for synthesis of 1,7-phenanthrolines. A study
of the Skraup reaction, when applied to meta and para-
phenylenediamines, with arsenic acid as the oxidizing
agent, revealed that the double Skraup reaction can be
satisfactorily applied with proper observation of important
factors, such as water concentration, method and time of
heating.10
Recently, Jacquelin etal.11 reportedthedoubleamination
of meta-diiodo and dibromobenzenes by anthranilic acid
derivates using palladium and/or copper catalysis. These
symmetrical and non-symmetrical phenylenediamines
were submitted to a cyclization/reduction/oxidation
synthetic sequence, being key precursors to polyfunctional
dibenzophenanthroline carboxaldehydes.
In addition, it has been observed that the introduction
of halogenated groups into organic molecules often
confers significant and useful changes in their physical,
chemical and biological properties.12-14 It is well known
that fluorocarbons are becoming increasingly important
in the medicinal, materials and agricultural fields. It has
been reported that the introduction of a trifluoromethyl
and its higher homologue CnF2n+1 groups into a heterocycle
frequently results in a much more potent activity than that
of the parent compounds, a fact which is probably related
to the high lipophilicity of perfluoroalkyl substituents.13,14
The vast majority of organofluorine compounds are not
natural products. Consequently, a synthetic methodology
to incorporate fluorine and fluorous synthons must be
optimized in order to prepare sophisticated fluoroorganic
molecules on a practical scale. One of the most satisfactory
methods for introducing a CF3 group into heterocycles is via
the trifluoromethylated building block approach.12,15-28 The
trifluoroacetylation of enol ethers or acetals provided, in
one step and in good yields, β-alkoxyvinyl trifluoromethyl
ketones 1 which proved to be useful building blocks for the
synthesis of many series of heterocyclic compounds.16,20,22-29
Ofnolessimportance, itisalsowellknownthatenamino-
carbonylcompoundsrepresentversatilesyntheticprecursors,
which combine the ambident nucleophilicity of enamines
with the ambident electrophilicity of enones, presenting
three nucleophilic and two electrophilic sites. For this reason,
enaminones have found a wide application in the synthesis
of various heterocycles, dyes and drugs.22,30-32
enaminoketones and their benzo[h]quinoline,25
dihydrobenzo[c]acridine,26 cycloalka[b]quinoline,27 and
1,2,3,4-tetrahydroacridine derivatives,28 we communicated
the synthesis of only three examples of 2,8- and
4,8-bis(trifluoromethyl)-1,7-phenanthrolines and
4-(trifluoromethyl)-7-aminoquinolineswheretwointeresting
intramolecular cyclization routes were found when
N,N’-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines were
heated at 165 ºC in polyphosphoric acid medium.29
The purpose of this paper is to report the complete results
of the reactions of 4-alkoxy-4-alkyl(aryl/heteroaryl)-1,1,1-
trifluoroalk-3-en-2-ones (1a-j) with 1,3-phenylenediamine
to obtain a wide series of ten examples of trifluoroacetyl
substituted 1,3-phenylene-bis-enamines (2a-j) and
also to investigate the chemical behavior of alkyl, aryl
and heteroaryl-substituted enamino intermediates (2)
for their application in the simultaneous regioselective
synthesis of new 2,8- or 4,8-bis(trifluoromethyl)-
2,10-bis-alkyl(aryl)-1,7-phenanthrolines (3) and the
respective 4-(trifluoromethyl)-7-aminoquinolines (4) under
similar reaction conditions as described previously.29
Results and Discussion
Firstly, a series of ten examples of 4-alkoxy-4-
alkyl(aryl/heteroaryl)-1,1,1-trifluoroalk-3-en-2-ones (1a-j),
which are readily available 1,3-dielectrophiles (CCC
synthetic blocks), were prepared from trifluoroacetylation
reactions of enol ethers commercially available (for 1a-b) or
generated in situ from the respective acetophenone dimethyl
acetal (for 1c-j) with trifluoroacetic anhydride, respectively,
in the presence of pyridine, as described in the literature.33
Second, a new series of ten bis-enaminone intermediates
2a-j was isolated in satisfactory yields of 47-91%, by
the reaction of enones 1a-j with 1,3-phenylenediamine
at a molar ratio of 2:1, respectively (Scheme 1). The
reactions can now be carried out in ethanol, water,
water/dichloromethane (1:1) or water/chloroform (1:1) at
a temperature range of 25 to 80 °C (Scheme 1). The best
results were obtained when enones 1a-j were added to
1,3-phenylenediamine, in pure ethanol for 1a-d and 1f-j
or in water/chloroform (1:1) solution for 1e. Good yields
were also obtained under other reaction conditions tested,
as above described. For example, the compounds 2b and
2g were obtained in good yields (85%) when the reactions
were carried out in water at room temperature as solvent.
However, the syntheses of enaminones 2a, 2f and 2h were
unsuccessful in an aqueous medium.
Specifically, we have described the synthesis of
N-[1-aryl(alkyl)-3-oxo-4,4,4-trifluoro(chloro)alken-1-yl]-
o-phenylenediamines23,24 from the reactions of 4-alkoxy-
1,1,1-trifluoroalk-3-en-2-ones with o-phenylenediamine
promoting cyclization reactions for benzodiazepine and
benzoimidazole derivatives.
The structures of compounds 2a-j were easily
established on the basis of 1H and 13C NMR spectroscopy.
In order to obtain structural information about the
Recently, applying the method previously described by
us for the preparation of some trifluoromethyl substituted

1428
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
R
O
R
O
O
OEt(Me)
R
i
+
N
H
N
H
47-91%
F3C
H2N
NH2
F3C
CF3
(1.0 equiv.)
1a-j (2.0 equiv.)
2a-j
1-2
a
b
c
d
e
f
g
h
i
j
R
H
Me Ph 4-MePh 4-OMePh 4-FPh 4-ClPh 4-BrPh 4-NO2Ph 2-Furyl
Scheme 1. Reagents and conditions: (i) = ethanol, 40 oC, 2 h (2a-d, f-k) or H2O/CHCl3 (1:1), 60 oC, 4 h (2e).
configuration of the compounds 2a-j we have performed
an 1H NMR study on (Z,Z)-N,N’-bis(3-oxo-4,4,4-trifluoro-
1-buten-1-yl)-1,3-phenylenediamine (2a). The H NMR
H3PO4) was prepared at 90 °C and the compounds 2a-j were
added to the acid mixture. The cyclization of 2a-j showed
that the best results were at 165 °C for 36 h, affording the
corresponding new angular series of bis-trifluoromethyl-
substituted 1,7-phenanthrolines 3a-i in 22-40% yields
(Scheme 2). Unfortunately, the above described general
and optimized conditions allowed us to obtain only traces
of the phenanthroline 3j derived from the enaminone 2j
(2-furyl derivative).
Accordingtotheliterature,itisknownthattheformationof
twopyridineringsfromderivativesofthe1,3-phenylenediamine
mayproceedintwopossiblewaystogivea1,7-phenanthroline
(3a, 5) or a benzodipyridine (6).8,9,29,36,37 It is also known that
intheformationofcycliccompoundsfromphenylenediamine
or quinoline derivatives, the angular structure is obtained in
preference to the linear one when both are possible.8,9,29,36 In
the present work, only derivatives of the angular structure
wereobtained,insteadofthelinearisomerbis-trifluoromethyl-
substituted pyrido[g]quinolines (6) (Scheme 2). However,
neither of the products isolated showed a mode of cyclization
similartothatobservedintheproductpreviouslyidentifiedby
usas2,8-bis(trifluoromethyl)-1,7-phenanthroline(3a).29 Only
the formation of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-
1,7-phenanthrolines (3b-i) was observed, as shown in
Scheme 2.
1
spectrum of 2a in CDCl3 showed (see SI) a cis coupling
constant for the vicinal olefin protons with J ca. 8 Hz,
which is consistent with a Z-configuration as the E- and
1
Z-forms can be easily distinguished by their H NMR
spectra because the N–H signals of the E-form (in 4-8 ppm)
appeared at a much higher field than those of the Z-form
(in 9-13 ppm), indicating the presence of an intramolecular
1
hydrogen bonding in the latter.34 The H NMR chemical
shifts of the enamino hydrogens (NH) for 2a-j were
observed on average of 12.20 ppm, allowing one to assume
that the enaminones 2a-j exist in the Z,Z-configuration in
CDCl3, which is stabilized by an intramolecular hydrogen
bond (N–H···OC) in each enaminone moiety. The proposed
Z-configuration was confirmed also by X-ray crystal
diffraction35 for compound 2g (Figure 2).
The structures of 3a-i were established on the basis of
1H and 13C NMR spectroscopies and also confirmed by
X-ray diffraction of 3a (Figure 3) and 3c (Figure 4). The
structure pattern of compound 3a is different from that of
3b-i, although obtained under similar reaction conditions.
For the 2,8-bis-trifluoromethyl-1,7-phenanthroline
(3a) the two CF3 groups occupy the nitrogen-adjacent
positions, suggesting the occurrence of two retro
1,4-cyclocondensations (hydrolysis and recombination) at
the same molecule 2a during the closure of the two pyridine
rings and following a mechanism already described in the
literature for a single cyclocondensation reaction, which
allowed the isolation of 2-trifluoromethyl-substituted
quinolines22,37-42 and benzo[h]quinolines.37,40
Figure 2. A perspective view of N,N’-bis(1-(4-chlorophenyl)-
4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2g) with atoms
labeled (CCDC 699774).35 Displacement ellipsoids are drawn at the in
50% probability level.
In a second reaction step, the acyclic enaminones 2a-j
were subjected to reactions carried out in the presence of a
strongly acidic medium (polyphosphoric acid, PPA), in the
absence of solvent. For all reactions, initially, PPA (P2O5 +

Vol. 22, No. 8, 2011
Bonacorso et al.
1429
CF3
N
F3C
N
R
R
N
N
F3C
5
6
CF3
F3C
CF3
3a (32%)
i
i
2a-j
CF3
N
N
R
R
CF3
R
N
N
N
R
NH2
R
N
CF3
R
N
F3C
3b-i (22-40%)
4b-j (20-73%)
F3C
R
7
2-7
a
b
c
d
e
f
g
h
i
j
R
H
Me Ph 4-MePh 4-OMePh 4-FPh 4-ClPh 4-BrPh 4-NO2Ph 2-Furyl
Scheme 2. Reagents and conditions: (i) = PPA, 165 oC, 36 h or PPA, 90 oC, 36 h (4j).
Figure 3. A perspective view of 2,8-bis(trifluoromethyl)-1,7-phenantroline
(3a) with atoms labeled (CCDC 699773).35 Displacement ellipsoids are
drawn at the in 50% probability level.
Figure 4. A perspective view of 4,8-bis(trifluoromethyl)-2,10-di(phenyl)-
1,7-phenanthroline (3c) with atoms labeled (CCDC 740919).35
Displacement ellipsoids are drawn at the in 50% probability level.
The 2,8-bis(trifluoromethyl)-1,7-phenanthroline
(3a) showed 13C NMR chemical shifts at 149.6 ppm (q,
2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a) showed
19F NMR signals at −67.12 and −67.26 ppm (CF3-2, CF3-8).
The 19F NMR spectra for compounds 2,10-dialkyl(aryl)-
4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b, c, g)
showed signals of CF3-4 at an average of −60.54 ppm
and for CF3-8 at an average of −67.28 ppm. The
spectroscopic data agree with 13C NMR and 19F NMR
chemical shift data for similar compounds described in the
literature.28-31,38
2
2JCF 34 Hz, C-2), 147.6 ppm (q, JCF 35 Hz, C-8) and
121.5 ppm (q, 1JCF 275 Hz, 2 CF3). The 13C NMR spectra of
the compounds 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-
1,7-phenanthrolines (3b-i) showed chemical shifts for
C-4 in the range of 133.1-136.2 ppm as a quartet with
2JCF ca. 31 Hz, for C-8 in the range of 148.2-151.1 ppm as
a quartet with 2JCF ca. 34 Hz, for CF3 groups in the range
of 120.6-123.4 ppm as a quartet with 1JCF ca. 275 Hz. The

1430
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
From the analysis of NMR data, we observed that one
With the synthesis of 4-CF3 quinolines, they reported
the 13C NMR spectral data and assigned the chemical
shift for the CF3 group for this regioisomer as quartets
at d 124.2 ppm (1JCF 275 Hz, CF3) and d 134.8 ppm
(2JCF 31 Hz, C4), respectively. In some cases, the reactions
resulted in mixtures of 2- and 4-CF3 quinolines.
ring closure occurred by a 1,2-cyclocondensation reaction,
while the other occurred by a retro 1,4-cyclocondensation.
Thus, one CF3 group is attached at the nitrogen-remote
position (4-CF3) andin the second ring and the CF3 group
is occupying the nitrogen-adjacent position (8-CF3). These
two different mechanisms are involved in the synthesis of
a series of 4,8-bis(trifluoromethyl)-1,7-phenanthrolines
(3b-i). Compounds 3 were separated from the reaction
mixture by a sublimation process during the heating of the
pure enaminone precursors 2, in PPA medium.
The possible formation of the 2,10-bis(trifluoromethyl)-
1,7-phenanthroline isomer (7, Scheme 2) was also excluded
because the 5-amino-4-(trifluoromethyl)quinolines were
not detected in the cyclization reactions from 2b-j. The
possible formation of the 4,10-bis(trifluoromethyl)-
1,7-phenanthroline isomer (5) was also excluded because
the CF-coupling on the NMR spectra should be present
as one quartet signal for the CF3 group and two identical
quartets for C-4 and C-10 in the narrow range of
d 147-150 ppm and no quartet signals should be expected
in the region of d 134-135 ppm.
On the other hand, the cyclization reactions of the
enaminones 2 by heating in acidic medium (PPA) could
result in the synthesis of the linear bis-trifluoromethyl-
substituted pyrido[g]quinolines (6), as reported in the
literature (Scheme 2).37 However, the NMR spectrum
should show four singlets for H-3, H-5, H-7 and H-10,
which were not observed, thus excluding the formation
of a linear isomer (pyrido[g]quinoline). In our case, all
spectroscopic data were consistent with the proposed
angular structures for phenanthrolines 3a-i, which are
preferably obtained according to the literature.7
The 2-alkyl(aryl/heteroaryl)-7-amino-4-(trifluoro-
methyl) quinolines (4b-j, Scheme 2) were obtained
in 20-73% yields, as by-products, from the reported
cyclization reactions and were isolated by recrystallization
after the work-up of residual reaction mixtures according to
the procedure described. We have attempted unsuccessfully
to obtain the phenanthrolines 3j-k under milder reaction
conditions than those described, but only quinoline 4j was
successfully isolated. The best result for 4j was obtained
when the reaction was carried out 90 °C for 24 h (73%
yield).
The structures of quinolines 4b-j were established on
the basis of 1H and 13C NMR spectroscopies and literature
data for similar compounds.36,39,40 The 13C NMR spectra
of the compounds 2-alkyl(aryl/heteroaryl)-7-amino-
4-(trifluoromethyl)quinolines (4b-j) showed chemical
shifts for C-4 in the range of 130.7-134.5 ppm as a quartet
2
with JCF ca. 31 Hz and for CF3 groups in the range of
1
118.3-125.5 ppm as a quartet with JCF ca. 275 Hz. The
19F NMR spectra of the compounds 2-alkyl(aryl/heteroaryl)-
7-amino-4-(trifluoromethyl)quinolines (4b, c, g, i) showed
signals of CF3-4 at an average of −62.26 ppm.
Schlosser et al.,39 who have investigated the synthesis
of 2- and 4-(trifluoromethyl)quinolines and quinolinones
in details, demonstrated a novel mode of isomerization and
cyclization in the synthesis of 2-(trifluoromethyl)quinolines
from anilines. As described, 4-anilino-l,l,l-trifluoro-
3-buten-2-ones can be readily obtained from the ethyl
trifluoroacetate derived 4-tert-butylamino-l,l,l-trifluorobut-
3-en-2-one by simple amine/amine replacement. Upon
heating in the presence of phosphoryl chloride, they
undergo ring closure to afford 2-(trifluoromethyl)quinolines
rather than the expected 4-isomers in 50% average yield.39
In subsequent experiments, Schlosser et al.41 determined
how 2-anilinovinyl perfluoroalkyl ketones can be
mechanistically correlated with their cyclization products
2-(perfluoroalkyl)quinolines. Their studies demonstrated
that some perfluoroalkyl-substituted 3-aminoenones, when
heated in the presence of phosphoryl chloride, cleaved
hydrolytically, setting free the substituted anilines and
the 1,3-dicarbonyl compounds. A proved recombination
of these subunits furnished unexpected 2-(CF2)nCF3-
quinolines.41
Then, based on experiments of Schlosser et al.41
to prove that a cleavage and a recombination reaction
occurred on enaminones 2, an equimolar mixture of
(Z,Z)-N,N’-bis(3-oxo-4,4,4-trifluorobut-1en-1-yl)-
1,3-phenylenediamine (2a) and p-toluidine was heated
at 165 °C for 36 h in the presence of PPA. The products
were identified by their gas chromatographic retention
times in comparison with those of authentic samples.
Thus, 65% of 6-methyl-2-(trifluoromethyl)quinoline,
25% of 2,8-bis(trifluoromethyl)-1,7-phenanthroline (3a)
and 11% of p-toluidine were identified after the reaction
work-up (Scheme 3). Thus, we think that the mechanism
suggested by Schlosser and co-workers may also explain
Linderman and Kirollos38 reported the synthesis of
2-CF3-substituted quinolines and assigned the chemical
shift for the CF3 group of the 13C NMR spectra as quartets
at d 122.3 ppm (1JCF 275 Hz, CF3) and at d 148.5 ppm
(2JCF 34 Hz, C2). In the same letter, another intramolecular
cyclization route was also described, which allowed the
synthesis of the 4-(trifluoromethyl)quinoline isomer.

Vol. 22, No. 8, 2011
Bonacorso et al.
1431
H3C
H3C
i
N
H
N
H
F3C
N
N
N
CF3
NH2
F3C
O
O
CF3
CF3
2a
3a
25%
65%
Scheme 3. Reagents and conditions: (i) = PPA, 165 oC, 36 h.
the unexpected findings of our work. We also think that
the starting material 2a afforded the 2,8-(CF3) product
(3a) “exclusively” but in only 32% yield, in absence
of p-toluidine, because the heating in presence of PPA
promoted the hydrolytic cleavage of the enaminone 2a
and a latter recombination also occurred but due to the
high reaction temperature (165 ºC), most of the volatile
4,4,4-trifluoro-3-oxobutanal escaped from the hot reaction
mixture in the course of the recombination reaction.
The isolation of quinolines 4b-j also suggests that a
hydrolysis reaction occurred in 2b-j, and the expected
recombination of the precursors to allow the synthesis of
phenanthrolines 3b-j, due to the high reaction temperature,
did not occur totally, probably because the dicarbonyl
compounds evaporated from the hot reaction mixtures.
The presented methodology used to obtain the
intermediate 1,3-phenylene-bis-trifluoromethyl substituted
enaminones (2a-j) showed satisfactory results. It can
be affirmed through the experimental data identified by
1H NMR and confirmed by X-ray crystal diffraction that
these synthetic intermediates 2a-j have a Z-configuration.
The procedure of its cyclization in strongly acidic
medium (PPA) proved to be feasible for the synthesis
of bis-trifluoromethyl-1,7-phenanthrolines (3a-i). The
interesting results reported herein regarding the chemical
behavior of these bis-enaminones 2a-j when subjected to
the cyclization reaction showed that the mode of cyclization
of unsubstituted bis-enaminone 2a (R1 = H) differs from
that of substituted bis-enaminones (R1 ≠ H) under the same
reaction conditions.
Conclusions
In summary, we have described an inexpensive
and unique route to prepare 1,7-phenanthroline and
7-aminoquinoline cores simultaneously. This process
might lead to greater molecular diversity of both
heterocyclic series, which are of great potential interest for
pharmacological and material applications.
Experimental
General
Unless otherwise indicated, all common reagents
and solvents were used as obtained from commercial
suppliers without further purification. The melting
points (mp) were determined using a Kofler Reichert-
Thermovar and Electrothermal Mel-Temp 3.0 apparatus.
1H, 13C and 19F NMR spectra were acquired on a Bruker
DPX 200 spectrometer (1H at 200.13 MHz) and Bruker
DPX 400 (1H at 400.13 MHz, 13C at 100.32 MHz and
19F at 376.3 MHz) spectrometer, 5 mm sample tubes,
298 K, digital resolution of 0.01 ppm, in CDCl3 for
1, 2, 3 and in DMSO-d6 for 4, using TMS as internal
reference (1H and 13C) or fluorobenzene as external
reference (19F). Mass spectra (MS) were registered in a
HP 6890 GC connected to a HP 5973 MSD and interfaced
by a Pentium PC. The gas chromatograph (GC) was
equipped with a split-splitless injector, autosampler,
cross-linked HP-5 capillary column (30 m, 0.32 mm of
internal diameter), and helium was used as the carrier
gas. The diffraction (XRD) measurements were carried
out by graphite-monochromatized Mo Kα radiation with
λ 0.71073 Å on a Bruker SMART CCD diffractometer.43
The structures of 2g, 3a and 3c were solved with direct
methods using SHELXS-97 program,44 and refined on F2
by full-matrix least-squares by the SHELXL-97 package.45
The absorption correction was performed by Gaussian
methods.46 Anisotropic displacement parameters for
non-hydrogen atoms were applied. The hydrogen atoms
were placed at calculated positions with 0.96 Å (methyl
CH3), 0.97 Å (methylene CH2), 0.98 Å (methyne CH),
Depending on the structure of the (Z,Z)-N,N’-
bis(oxotrifluoroalkenyl)-1,3-phenylenediamines (2),
2,8-bis-(trifluoromethyl)-1,7-phenanthroline or a mixture of
separable 4,8-bis-(trifluoromethyl)-1,7-phenanthrolines and
4-(trifluoromethyl)-7-aminoquinolines was obtained. These
resultsreportedhereshowedaninterestingchemicalbehavior
forthemechanismofcyclizationofthesenewenaminoketones
2, showing selective routes of ring closure including direct
cyclocondensations, hydrolyses and recombinations, which
furnished new fused bis-(trifluoromethyl)-diazatricycles.
Linear bis(trifluoromethyl)-pyrido[g]quinolines (6)
compounds were not isolated.

1432
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
0.93 Å (aromatic CH) using a riding model. The
hydrogen isotropic thermal parameters were kept equal to
Uiso(H) = χUeq (carrier C atom), with χ = 1.5 for methyl
groups and χ = 1.2 otherwise. The valence angles C−C−H
and H−C−H of methyl groups were set to 109.5º and the
H atoms were allowed to rotate around the C−C bond.
A molecular graph was prepared using ORTEP3 for
Windows.47 The CHN elemental analyses were performed
on a Perkin-Elmer 2400 CHN elemental analyzer (São
Paulo University, USP/Brazil).
(CDCl3) d 177.1 (q, 2J 34 Hz, 2 C-3), 167.2 (2 C-1), 138.2
(2 C, C-5, C-7), 130.5 (C-6), 123.8 (2 C, C-8, C-10), 121.7
(C-9), 117.2 (q, 1J 288 Hz, 2 CF3), 91.5 (q, 3J 1 Hz, 2 C-2),
20.3 (2 CH3); GC-MS (EI, 70 eV, m/z) 199 (100), 380 (M+,
75), 311 (40), 283 (55), 265 (48), 69 (7%); Anal. calcd.
for C26H14F6N2O2 (380.10): C, 50.53; H, 3.71; N, 7.37%.
Found: C, 50.85; H, 3.81; N, 7.61%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-phenyl-3-oxo-1-buten-
1-yl)-1,3-phenylenediamine (2c)
Yellow solid (2.01 g, 80% yield); mp 190-192 °C;
1H NMR (CDCl3) d 12.20 (s, 2H, NH), 7.49-7.19 (m,
10H, Ph), 6.94 (t, 1H, J 8 Hz, H-9), 6.52 (d, 2H, J 8 Hz,
H-8, H-10), 6.40 (s, 1H, H-6), 5.70 (s, 2H, H-2); 13C NMR
(CDCl3) d 178.1 (q, 2J 34 Hz, 2 C-3), 166.1 (2 C-1), 138.8
(2 C, C-5, C-7), 133.5 (2 C-Ph), 130.9 (C-6), 129.4, 128.8,
128.2 (10 C-Ph), 121.7 (2 C, C-8, C-10), 119.5 (C-9),
General procedure for the synthesis of N,N’-bis(1-
alkyl[aryl(heteroaryl)]-4,4,4-trifluoro-3-oxo-1-buten-
1-yl)-1,3-phenylenediamines (2a-j)
To a stirred solution of 1,3-phenylenediamine (0.54 g,
5 mmol) in ethanol (10 mL), 1a-j (10 mmol) was added
at room temperature. The mixture was stirred at 40 °C for
2 h. After the end of the reaction (TLC), the resulting solid
products 2a-j were isolated by filtration (1st fraction: 80%).
Subsequently, the filtrates were evaporated under reduced
pressure and the residues were dissolved in hot chloroform
and stirred with activated charcoal. After filtration, the
filtrates were evaporated under reduced pressure. Then,
the crude oily products 2 were dissolved in hot ethanol and
subsequently cooled (4-8 °C, 48 h) to give 2 as powders
(2nd fraction: 20%). Finally, both fractions were combined
and gathered and recrystallized from chloroform (26-91%
yields).
1
117.15 (q, J 289 Hz, 2 CF3), 93.1 (2 C-2); GC-MS (EI,
70 eV, m/z) 504 (M+, 30), 435 (22), 407 (100), 323 (30),
69 (2%);Anal. calcd. for C26H18F6N2O2 (504.13): C, 61.91;
H, 3.60; N, 5.55%. Found: C, 62.02; H, 3.75; N, 5.64%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-[4-methylphenyl]-3-oxo-
1-buten-1-yl)-1,3-phenylenediamine (2d)
Brown solid (2.29 g, 86% yield); mp 138-140 °C;
1H NMR (CDCl3) d 12.20 (s, 2H, NH), 7.12 (d, 4H, J 8 Hz,
Ph), 7.16 (d, 4H, J 8 Hz, Ph), 6.96 (t, J 8 Hz, 1H, H-9),
6.54 (dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 6.41 (s, 1H, H-6),
5.69 (s, 2H, H-2), 2,33 (s, 6H, 2 CH3); 13C NMR (CDCl3)
d 178.0 (q, 2J 34 Hz, 2 C-3), 166.3 (2 C-1), 141.6 (2 C-Ph),
139.2 (2 C, C-5, C-7), 130.7 (C-6), 129.5, 129.4, 128.3
(10 C-Ph), 121.6 (2 C, C-8, C-10), 119.5 (C-9), 117.3 (q,
1J 289 Hz, 2 CF3), 93.0 (2 C-2), 21.3 (2 CH3); GC-MS
(EI, 70 eV, m/z) 435 (100), 532 (M+, 21), 463 (17), 351
(21), 222 (15), 69 (5%); Anal. calcd. for C28H22F6N2O2
(532.16): C, 63.16; H, 4.16; N, 5.26%. Found: C, 63.02;
H, 4.21; N, 5.30%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-3-oxo-1-buten-1-yl)-
1,3-phenylenediamine (2a)32
Beige solid (1.20 g, 68% yield); mp 171-173 °C;
1H NMR (CDCl3) d 11.74 (d, 2H, J 12 Hz, NH), 7.63 (dd,
2H, J1 8, J2 12 Hz, H-1), 7.41 (t, 1H, J 8 Hz, H-9), 6.95 (dd,
H-8, J1 2, J2 8 Hz, 2H, H-10), 6.86 (t, 1H, J 2 Hz, H-6),
5.71 (d, 2H, J 8 Hz, H-2); 13C NMR (CDCl3) d 179.3 (q, 2J
34 Hz, 2 C-3), 149.3 (2 C-1), 140.3 (2 C, C-5, C-7), 131.3
(C-6), 116.5 (q, 1J 289 Hz, 2 CF3), 113.8 (2 C, C-8, C-10),
105.7 (C-9), 90.3 (2 C-2); 19F (CDCl3) d −75.35 (2-CF3);
GC-MS (EI, 70 eV, m/z) 352 (M+, 100), 283 (55), 213
(23), 185 (33), 107 (24), 263 (11), 69 (5%); Anal. calcd.
for C14H10F6N2O2 (352.06): C, 47.74; H, 2.86; N, 7.95%.
Found: C, 48.03; H, 2.96; N, 7.85%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-[4-methoxyphenyl]-
3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2e)
To a stirred solution of 1,3-phenylenediamine (0.54 g,
5 mmol) in H2O:CHCl3 (1:1, 10 mL), 1e (2.60 g, 10 mmol)
was added at room temperature. The mixture was stirred
for 4 h at 60 °C. After the end of the reaction (TLC), the
resulting residue was extracted with dichloromethane. Then
the organic layer was evaporated under reduced pressure.
Then, the crude oily product was dissolved in hot ethanol
and subsequently cooled (4-8 °C, 48 h) to give the title
compound 2e.
(Z,Z)-N,N’-bis(5,5,5-Trifluoro-4-oxo-2-penten-2-yl)-
1,3-phenylenediamine (2b)
Brown solid (1.63 g, 86% yield); mp 126-128 °C;
1H NMR (CDCl3) d 12.58 (s, 2H, NH), 7.48 (t, 1H, J 8 Hz,
H-9), 7.14 (dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 7.01 (s,
1H, H-6), 5.59 (s, 2H, H-2), 2.15 (s, 6H, CH3); 13C NMR
Beige solid (1.32 g, 47% yield), mp 142-144 °C;
1H NMR (CDCl3) d 12.22 (s, 2H, NH), 7.19 (d, 4H,

Vol. 22, No. 8, 2011
Bonacorso et al.
1433
J 9 Hz, Ph), 6.98 (t, 1H, J 8 Hz, H9), 6.85 (d, 4H, J 9 Hz,
Ph), 6.55 (dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 6.48 (s, 1H,
H-6), 5.69 (s, 2H, H-2), 3.84 (s, 6H, 2 OCH3); 13C NMR
(CDCl3) d 177.6 (q, 2J 34 Hz, 2 C-3), 165.9 (2 C-1), 161.8
(2 C-Ph), 139.3 (2 C, C-5, C-7), 130.1 (4 C-Ph), 129.5
(C-6), 125.3 (2 C-Ph), 121.7 (2 C, C-8, C-10), 119.5 (C-9),
132.4, 132.2, 131.0, 129.8 (12 C-Ph), 125.6 (C-6), 122.2
(2 C, C-8, C-10), 119.7 (C-9), 116.6 (q, 1J 289 Hz, 2 CF3),
93.3 (2 C-2); GC-MS (EI, 70 eV, m/z) 659 (M+, 17), 549
(100), 286 (30), 69 (9%);Anal. calcd. for C26H16Br2F6N2O2
(659.95): C, 47.16; H, 2.44; N, 4.23%. Found: C, 47.25;
H, 2.45; N, 4.34%.
1
114.2 (4 C-Ph), 117.1 (q, J 289, 2 CF3), 92.7 (2 C-2),
55.4 (2 OCH3); GC-MS (EI, 70 eV, m/z) 564 (M+, 21), 281
(70), 207 (100), 96 (10%); Anal. calcd. for C28H22F6N2O4
(564.15): C, 59.58; H, 3.93; N, 4.96%. Found: C, 59.55;
H, 3.89; N, 4.98%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-(4-nitrophenyl)-3-oxo-
1-buten-1-yl)-1,3-phenylenediamine (2i)
Beige solid (2.64 g, 89% yield); mp 220-222 °C;
1H NMR (CDCl3) d 12.13 (s, 2H, NH), 8.24 (dd, 4H, J 2,
J 8 Hz, Ph), 7.45 (dd, 4H, J1 2, J2 8 Hz, Ph), 6.95 (t, 1H,
J 8 Hz, H-9), 6.58 (t, 1H, J 2 Hz, H-6), 6.46 (dd, 2H, J1 2,
J2 8 Hz, H-8, H-10), 5.74 (s, 2H, H-2); 13C NMR (CDCl3)
d 178.5 (q, 2J 34 Hz, 2 C-3), 165.4 (2 C-1), 146.3, 145.9
(4 C-Ph), 138.8 (2 C, C-5, C-7), 132.2, 129.7 (8 C-Ph),
125.6 (C-6), 122.2 (2 C, C-8, C-10), 119.8 (C-9), 117.2 (q,
1J 289 Hz, 2 CF3), 92.9 (2 C-2); GC-MS (EI, 70 eV, m/z)
594 (M+, 15), 525 (30), 497 (100), 69 (10%); Anal. calcd.
for C26H16F6N4O6 (594.10): C, 52.54; H, 2.71; N, 9.43%.
Found: C, 52.60; H, 2.70; N, 9.47%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-[4-fluorophenyl]-3-oxo-
1-buten-1-yl)-1,3-phenylenediamine (2f)
Beige solid (1.67 g, 62% yield); mp 177-179 °C;
1H NMR (CDCl3) d 12.20 (s, 2H, NH), 7.28-7.21 (m, 4H,
Ph), 7.11-6.95 (m, 4H, Ph), 6.98 (t, 1H, J 8 Hz, H9), 6.53
(dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 6.51 (s, 1H, H-6), 5.69 (s,
2H, H-2); 13C NMR (CDCl3) d 178.1 (q, 2J 34 Hz, 2 C-3),
163.9 (d, 1J 253 Hz, 2 C-FPh), 164.9 (2 C-1), 138.9 (2 C,
C-5, C-7), 130.5 (d, 3J 9 Hz, 4 C-FPh), 129.6 (C-6), 129.5
(d,4J 3 Hz, 2 C-FPh), 122.0 (2 C, C-8, C-10), 119.7 (C-6),
117.0 (q, 1J 289 Hz, 2 CF3), 116.1 (d, 2J 22 Hz, 4 C-FPh),
93.2 (2 C-2);GC-MS (EI, 70 eV, m/z) 540 (M+, 20), 471
(20), 443 (100), 255 (30), 226 (30), 69 (10%);Anal. calcd.
for C26H16F8N2O2 (540.11): C, 57.79; H, 2.98; N, 5.18%.
Found: C, 57.63; H, 2.99; N, 5.19%.
(Z,Z)-N,N’-bis(4,4,4-Trifluoro-1-[2-furyl]-3-oxo-1-buten-
1-yl)-1,3-phenylenediamine (2j)
Yellow solid (1.72 g, 71% yield); mp 210-212 °C;
1H NMR (CDCl3) d 12.23 (s, 2H, NH), 7.46 (s, 2H, furyl),
7.34 (t, 1H, J 8 Hz, H-9), 7.04 (dd, 2H, J1 2, J2 8 Hz, H-8,
H-10), 6.83 (s, 1H, H-6), 6.45-6.41 (m, 4H, furyl), 6.09 (s,
2H, H-2); 13C NMR (CDCl3) d 178.2 (q, 2J 34 Hz, 2 C-3),
153.9 (2 C-1), 145.8, 145.6 (4 C-furyl), 139.7 (2 C, C-5,
C-7), 130.1 (C-6), 123.6 (2 C, C-8, C-10), 121.4 (C-9),
117.3 (q, 1J 288 Hz, 2 CF3), 117.2, 112.6 (4 C-furyl), 89.2
(2 C-2); GC-MS (EI, 70 eV, m/z) 484 (M+, 15), 415 (21),
387 (100), 227 (14), 69 (7%);Anal. calcd. for C22H14F6N2O4
(484.09): C, 54.55; H, 2.91; N, 5.78%. Found: C, 54.57;
H, 2.90; N, 5.82%.
(Z,Z)-N,N’-[1-[4-Chlorophenyl]-4,4,4-trifluoro-3-oxo-
1-buten-1-yl]-1,3-phenylenediamine (2g)
Brown solid (2.37 g, 83% yield); mp 175-177 °C;
1H NMR (CDCl3) d 12.16 (s, 2H, NH), 7.34 (d, 4H, J 9 Hz,
Ph), 7.17 (d, 4H, J 9 Hz, Ph), 6.99 (t, 1H, J 8 Hz, H-9),
6.53 (dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 6.50 (s, 1H, H-6),
5.68 (s, 2H, H-2); 13C NMR (CDCl3) d 178.2 (q, 2J 34 Hz,
2 C-3), 164.6 (2 C-1), 138.8 (2 C, C-5, C-7), 131.9 (C-6),
129.8, 129.7, 129.6, 129.2, 128.9 (12 C-Ph), 122.2 (2 C,
C-8, C-10), 119.7 (C-9), 116.9 (q, 1J 289 Hz, 2 CF3), 93.2
(2 C-2); GC-MS (EI, 70 eV, m/z) 572 (M+, 17), 475 (100),
433 (7), 391 (34), 242 (30), 213 (4), 69 (5%); Anal. calcd.
for C26H16F6N2O2 (572.05): C, 54.54; H, 2.79; N, 4.89%.
Found: C, 54.57; H, 2.87; N, 4.99%.
General procedure for the synthesis of 2,8-bis(trifluoro-
methyl)-1,7-phenantroline (3a), 2,10-dialkyl(aryl)-
4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b-i) and
2-alkyl(aryl)-7-aminoquinolines (4b-i)
To a stirred mixture of H3PO4 (2 mL) and P2O5 (3 g)
(PPA) at 90 °C, 2a-j (2 mmol) was added. Using a 10 cm
length glass adapter connecting the flask reaction and the
condenser, the mixture was stirred at 165 °C for 36 h.After
this time, the sublimated products 3a-i were recovered
from the adapter using chloroform and the remaining
amounts of 3 in the reaction flask were also extracted with
chloroform. Both organic fractions were recrystallized from
chloroform (22-40% yields). To the dark residue remainder
(Z,Z)-N,N’-bis(1-[4-Bromophenyl]-4,4,4-trifluoro-3-oxo-
1-buten-1-yl)-1,3-phenylenediamine (2h)
Beige solid (3.00 g, 91% yield); mp 170-172 °C;
1H NMR (CDCl3) d 12.20 (s, 2H, NH), 7.51 (d, 4H,
J 9 Hz, Ph), 7.10 (d, 4H, J 9 Hz, Ph), 6.99 (t, 1H, J 8 Hz,
H-9), 6.53 (dd, 2H, J1 2, J2 8 Hz, H-8, H-10), 6.51 (s, 1H,
H-6), 5.69 (s, 2H, H-2); 13C NMR (CDCl3) d 178.4 (q,
2J 34 Hz, 2 C-3), 164.7 (2 C-1), 138.9 (2 C, C-5, C-7),

1434
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
1
in the reaction flask were added 20 g of crushed ice and
ethyl acetate (20 mL).After stirring, the 7-aminoquinolines
(4b-j) were isolated when the aqueous phase was extracted
with ethyl acetate (6 × 20 mL) combined with NaOH sol.
40% (5 mL). The organic layer was washed with distilled
water (3 × 15 mL) and dried over sodium sulfate. After
filtration, the liquid phase was stirred and heated in the
presence of activated charcoal, filtered again and the
solvent was removed under reduced pressure. The resulting
powders (4b-j) were recrystallized from a mixture of ethyl
acetate/hexane (3:1 v/v) (20-45% yields).
(10 C-Ph), 127.3 (C-6), 127.2 (C-5), 123.4 (q, J 275 Hz,
3
CF3), 122.3 (q, J 5 Hz, C-3), 122.0 (C-4a), 121.4 (q,
1J 275 Hz, CF3), 115.5 (q, 3J 5 Hz, C-9); 19F NMR (CDCl3)
d −60.40 (CF3-4), −67.38 (CF3-8); GC-MS (EI, 70 eV, m/z)
468 (M+, 100), 449 (12), 399 (37), 226 (20), 198 (19), 137
(5%);Anal. calcd. forC26H14F6N2(468.11):C, 66.67;H, 3.01;
N, 5.98%. Found: C, 66.71; H, 3.25; N, 6.04%.
4,8-bis(Trifluoromethyl)-2,10-di(4-methylphenyl)-
1,7-phenanthroline (3d)
Yellow solid (0.32 g, 28% yield); mp 230-232 °C;
1H NMR (CDCl3) d 8.00 (d, 4H, J 8 Hz, Ph), 7.86 (d, 1H,
J2 9 Hz, H-6), 7.82 (dq, 1H, J1 2, J2 8 Hz, H-5), 7.84 (s, 1H,
H-3), 7.72 (s, 1H, H-9), 7.32 (d, 4H, J 8 Hz, Ph), 2.47 (s, 3H,
CH3), 2.42 (s, 3H, CH3); 13C NMR (CDCl3) d 155.3 (C-10),
153.5 (C-2), 151.1 (C-10b), 149.6 (q, 2J 34 Hz, C-8), 147.5
(C-6a), 139.8, 136.7 (4 C-Ph), 135.2 (q, J 31 Hz, C-4),
130.1 (C-10a), 129.5, 128.3 (8 C-Ph), 125.9 (C-6), 123.4
(q, 1J 275 Hz, CF3), 121.4 (q, 1J 275 Hz, CF3), 120.5 (C-5),
120.1 (C-4a) 117.4 (q, J 3 Hz, C-3), 115.5 (q, J 5 Hz,
C-9), 22.9 (CH3), 21.1(CH3); GC-MS (EI, 70 eV, m/z) 496
(M+, 100), 477 (10), 427 (35%);Anal. calcd. for C28H18F6N2
(496.14): C, 67.74; H, 3.65; N, 5.64%. Found: C, 67.81;
H, 3.74; N, 5.68%.
2,8-bis(Trifluoromethyl)-1,7-phenantroline (3a)32
Yellow solid (0.20 g, 32% yield); mp 131-133 °C;
1H NMR (CDCl3) d 9.79 (d, 1H, J 9 Hz, H-10), 8.48 (d, 1H,
J 8 Hz, H-4), 8.27 (d, 1H, J 9 Hz, H-3), 8.11 (d, 1H, J 9 Hz,
H-9), 8.03 (d, 1H, J 8 Hz, H-5), 8.01 (d, 1H, J 8 Hz, H-6);
13C NMR (CDCl3) d 149.6 (q, 2J 35 Hz, C-2), 149.0 (C-10b),
147.6 (q, 2J 35 Hz, C-8), 144.6 (C-6a), 137.8 (C-10), 135.2
(C-4), 130.9 (C-6), 129.7 (C-5), 128.0 (C-10a), 127.9
2
3
3
1
(C-4a), 121.5 (q, J 275 Hz, 2 CF3), 119.2 (C-3), 118.4
(C-9); GC-MS (EI, 70 eV, m/z) 316 (M+, 100), 297 (16),
247 (77), 227 (17), 177 (28), 69 (5%); Anal. calcd. for
C14H6F6N2 (316.20): C, 53.18; H, 1.91; N, 8.86%. Found:
C, 53.34; H 2.01; N, 8.91%.
4,8-bis(Trifluoromethyl)-2,10-di(4-methoxyphenyl)-
1,7-phenanthroline (3e)
4 , 8 - b i s ( Tr i f l u o ro m e t h y l ) - 2 , 1 0 - d i ( m e t h y l ) -
1,7-phenanthroline (3b)32
Yellow solid (0.23 g, 22% yield); mp 246 -248 °C;
1H NMR (CDCl3) d 8.15 (dd, J1 2, J2 8 Hz, 4H, Ph), 8.97
(dq, 1H, J1 2, J2 8 Hz, H-5), 7.12 (dd, 4H, J1 2, J2 8 Hz, Ph),
7.08 (d, 1H, J 2 Hz, H-6), 6.98 (s, 2H, H-3, H-9), 3.89 (s,
6H, OCH3); 13C NMR (CDCl3) d 155.5 (C-10), 153.7 (C-2),
151.3 (C-10b), 149.2 (q, 2J 34 Hz, C-8), 147.7 (C-6a), 144.5
(2 C-Ph), 136.2 (q, 2J 31 Hz, C-4), 132.7 (C-10a), 130.8,
130.6 (6 C-Ph), 129.8 (C-6), 129.4 (C-5), 128.0 (q, 3J 5 Hz,
Yellow solid (0.26 g, 38% yield); mp 147-149 °C;
1H NMR (CDCl3) d 8.23 (dq, 1H, J1 2, J2 8 Hz, H-5), 8.15 (d,
1H, J 8 Hz, H-6), 7.74 (s, 1H, H-3), 7.70 (s, 1H, H-9), 3.33
(s, 3H, CH3), 2.86 (s, 3H, CH3); 13C NMR (CDCl3) d 157.1
(C-10), 151.5 (C-2), 149.6 (C-10b), 148.0 (C-6a), 147.6 (q,
2J 34 Hz, C-8), 134.3 (q, 2J 31 Hz, C-4), 130.5 (C-10a), 126.5
(C-6), 125.2 (q, 4J 3 Hz, C-5), 121.6 (q, 3J 5 Hz, C-3), 120.0
(C-4a), 124.0 (q, 1J 275 Hz, CF3), 123.4 (q, 1J 275 Hz, CF3),
118.5 (q, 3J 5 Hz, C-9), 27.2 (CH3), 25.1 (CH3); 19F NMR
(CDCl3) d −60.36 (CF3-4), −67.34 (CF3-8); GC-MS (EI, 70
eV, m/z) 344 (M+, 100), 325 (19), 275 (19), 172 (8), 69 (6%);
Anal. calcd. for C16H10F6N2 (344.25): C, 55.77; H, 2.90; N,
8.13%. Found: C, 55.48; H, 3.14; N, 8.03%.
1
C-3), 127.6 (C-4a), 124.9 (4 C-Ph), 124.0 (q, J 275 Hz,
CF3), 122.8 (q, 1J 275 Hz, CF3), 117.6 (q, 3J 5 Hz, C-9), 54.5
(OCH3), 52.3 (OCH3); GC-MS (EI, 70 eV, m/z) 528 (M+,
100), 509 (14), 459 (38%); Anal. calcd. for C28H18F6N2O2
(528.13): C, 63.64; H, 3.43; N, 5.30%. Found: C, 63.59;
H, 3.38; N, 5.41%.
4 , 8 - b i s ( Tr i f l u o ro m e t h y l ) - 2 , 1 0 - d i ( p h e n y l ) -
1,7-phenanthroline (3c)
4,8-bis(Trifluoromethyl)-2,10-di(4-fluorophenyl)-
1,7-phenanthroline (3f)
Yellow solid (0.37 g, 40% yield); mp 226-228 °C;
1H NMR (CDCl3) d 8.39 (dq, 1H, J1 2, J2 8 Hz, H-5), 8.32
(d, 1H, J 9 Hz, H-6), 8.27 (s, 1H, H-3), 7.80 (s, 1H, H-9),
7.50-7.41 (m, 5H, Ph), 7.39-7.25 (m, 5H, Ph); 13C NMR
(CDCl3) d 154.4 (C-10), 152.6 (C-2), 150.2 (C-10b), 148.2
(q, 2J 34 Hz, C-8), 146.7 (C-6a), 143.5, 136.7 (2 C-Ph), 135.2
(q, 2J 31 Hz, C-4), 130.7 (C-10a), 130.1, 128.7, 128.6, 127.7
Yellow solid (0.29 g, 29% yield); mp 234-236 °C;
1H NMR (CDCl3) d 8.15-8.08 (m, 2H, Ph), 7.86 (dq, 1H,
J1 2, J2 8 Hz, H-5), 7.76 (s, 1H, H-6), 7.43-7.39 (m, 2H,
Ph), 7.23 (s, 1H, H-3), 7.19-7.14 (m, 2H, Ph), 7.01 (s, 1H,
H-9), 7.01-6.94 (m, 2H, Ph); 13C NMR (CDCl3) d 162.3
(d, 1J 253 Hz, 2 C-FPh), 155.1 (C-10), 154.2 (C-2), 153.3
2
(C-10b), 148.6 (q, J 34 Hz, C-8), 146.1 (C-6a), 133.1

Vol. 22, No. 8, 2011
Bonacorso et al.
1435
2
2
(q, J 31 Hz, C-4), 130.3 (d, 4J 3 Hz, 2 C-FPh), 129.1
(C-10a), 128.3 (d,3J 8 Hz, 4 C-FPh), 122.2 (C-6), 123.4 (q,
1J 275 Hz, CF3), 121.4 (q, 1J 275 Hz, CF3), 117.6 (q, 3J 5 Hz,
147.8 (C-6a), 147.4, 143.9 (4 C-Ph), 134.3 (q, J 31 Hz,
C-4), 131.4 (C-10a), 130.0 (4 C-Ph), 126.5 (C-6), 125.2 (q,
4J 3 Hz, C-5), 124.5 (4 C-Ph), 123.4 (q, 1J 275 Hz, CF3),
121.5 (q, 1J 275 Hz, CF3), 121.6 (q, 3J 5 Hz, C-3), 120.9
2
C-5), 115.4 (C-4a), 114.4 (d, J 22 Hz, 4 C-FPh), 114.2
(C-3), 112.8 (C-9); GC-MS (EI, 70 eV, m/z) 503 (M+, 100),
485 (7), 435 (18), 409 (16%); Anal. calcd. for C26H12F8N2
(504.09): C, 61.91; H, 2.40; N, 5.55%. Found: C, 61.95;
H, 2.53; N, 5.64%.
(C-4a), 118.4 (q, J 5 Hz, C-9); GC-MS (EI, 70 eV, m/z)
3
558 (M+, 100), 539 (18), 489 (30), 69 (10%); Anal. calcd.
for C26H12F6N4O4 (558.08): C, 55.92; H, 2.17, N; 10.03%.
Found: C, 55.88; H, 2.28; N, 10.21%.
2,10-di(4-Chlorophenyl)-4,8-bis(trifluoromethyl)-
1,7-phenanthroline (3g)
4-Trifluoromethyl-2-methyl-7-aminoquinoline (4b)32
Brown solid (0.18 g, 40% yield); mp 174-176 °C;
1H NMR (CDCl3) d 7.87 (dq, 1H, J1 2, J2 9 Hz, H-5),
7.30 (s, 1H, H-3), 7.21 (d, 1H, J 2 Hz, H-8), 7.02 (dd, 1H,
J1 2, J2 9 Hz, H-6), 4.18 (s, 2H, NH), 2.72 (s, 3H, CH3);
13C NMR (DMSO-d6) d 158.1 (C-2), 150.7 (C-8a), 150.6
(C-7), 132.2 (q, 2J 30 Hz, C-4), 123.6 (C-5), 119.5 (C-6),
118.3 (q, 1J 275 Hz, CF3), 113.5 (q, 3J 5 Hz, C-3), 112.2
(C-4a), 106.8 (C-8), 24.7 (CH3); 19F NMR (376 MHz,
CDCl3) d −61.25 (CF3-4); GC-MS (EI, 70 eV, m/z) 226
(M+, 100), 210 (7), 199 (31), 157 (8), 142 (7), 69 (6%);
Anal. calcd. for C11H9F3N2 (226.07): C, 58.41; H, 4.01; N,
12.38%. Found: C, 58.04; H, 4.01; N, 12.01%.
Yellow solid (0.37 g, 35% yield); mp 236-238 °C;
1H NMR (CDCl3) d 8.39 (dq, 1H, J1 2, J2 8 Hz, H-5), 8.34
(d, 1H, J 2 Hz, H-6), 8.23 (s, 1H, H-3), 7.76 (s, 1H, H-9),
7.49-7.46 (m, 2H, Ph), 7.37-7.35 (m, 4H, Ph), 7.24-7.21
(m, 2H, Ph); 13C NMR (CDCl3) d 153.2 (C-10), 152.5
2
(C-2), 151.6 (C-10b), 151.1 (q, J 34 Hz, C-8), 148.2
2
(C-6a), 137.8, 135.3 (4 C-Ph), 134.1 (q, J 31 Hz, C-4),
131.5 (C-10a), 130.9, 169.7 (8 C-Ph), 128.0 (C-6), 126.4
(C-5), 123.6 (q, 1J 275 Hz, CF3), 121.5 (q, 1J 275 Hz, CF3),
3
3
119.5 (q, J 5 Hz, C-3), 119.3 (C-4a), 118.1 (q, J 5 Hz,
C-9); 19F NMR (CDCl3) d −60.59 (CF3-4), −67.57 (CF3-8);
GC-MS (EI, 70 eV, m/z) 535 (M+, 100), 501 (20), 467 (12),
425 (12), 232.6 (14), 198 (14), 138 (5%); Anal. calcd. for
C26H14F6N2 (536.02): C, 58.12; H, 2.25; N, 5.21%. Found:
C, 58.21; H, 2.32; N, 5.18%.
4-Trifluoromethyl-2-phenyl-7-aminoquinoline (4c)
Brown solid (0.22 g, 38% yield); mp 139-141 °C;
1H NMR (DMSO-d6) d 8.25 (dd, 2H, J1 2, J2 8 Hz, Ph), 7.95
(s, 1H, H-3), 7.79 (dq, 2H, J1 2, J2 8 Hz, H-5), 7.57-7.51 (m,
3H, Ph), 7.21 (d, 1H, J 2 Hz, H-6), 7.16 (s, 1H, H-8), 6.15
(s, 2H, NH2); 13C NMR (DMSO-d6) d 155.4 (C-2), 151.0
(C-8a), 150.9 (C-7), 138.1 (C-Ph), 130.7 (q, 2J 30 Hz, C-4),
2,10-di(4-Bromophenyl)-4,8-bis(trifluoromethyl)-
1,7-phenanthroline (3h)
Yellow solid (0.43 g, 33% yield); mp 262-264 °C;
1H NMR (CDCl3) d 8.35 (s, 1H, H-3), 8.22 (s, 1H, H-9),
7.95 (dq, 1H, J1 2, J2 8 Hz, H-5), 7.78 (d, 1H, J 2 Hz, H-6),
7.58 (dd, 4H, J1 2, J2 8 Hz, Ph), 7.21 (dd, 4H, J1 2, J2 8 Hz,
Ph); 13C NMR (CDCl3) d 152.8 (C-10), 152.2 (C-2), 151.2
1
129.6, 128.7, 127.0 (5 C-Ph), 123.8 (q, J 275 Hz, CF3),
123.7 (C-5), 120.5 (C-6), 113.0 (C-4a), 110.0 (q, 3J 5 Hz,
C-3), 107.3 (C-8); 19F NMR (CDCl3) d −61.28 (CF3-4);
GC-MS (EI, 70 eV, m/z) 288 (M+, 100), 273 (5), 219 (20),
203 (5%); Anal. calcd. for C16H11F3N2 (288.09): C, 66.66;
H, 3.85; N, 9.72%. Found: C, 66.32; H, 3.75; N, 9.64%.
2
(C-10b), 149.3 (q, J 34 Hz, C-8), 137.5 (C-6a), 134.9
(2 C-Ph), 133.8 (q, 2J 31 Hz, C-4), 132.0 (C-10a), 131.2,
130.6, 129.3 (10 C-Ph), 127.7 (C-6), 125.6 (C-5), 123.5
1
1
(q, J 275 Hz, CF3), 121.5 (q, J 275 Hz, CF3), 119.4 (q,
3J 5 Hz, C-3), 118.9 (C-4a), 117.8 (q, 3J 5 Hz, C-9); GC-MS
(EI, 70 eV, m/z) 625 (M+, 100), 554 (23), 468 (5), 69 (8%);
Anal. calcd. for C26H12Br2F6N2 (623.93): C, 49.87; H, 1.93;
N, 4.47%. Found: C, 49.83; H, 2.01; N, 4.58%.
4-Trifluoromethyl-2-(4-methylphenyl)-7-aminoquinoline
(4d)
Yellow brown (0.14 g, 24% yield); mp 156-158 °C;
1H NMR (CDCl3) d 8.03 (d, 2H, J 8 Hz, Ph), 7.91 (dq, 2H,
J1 2, J2 9 Hz, H-5), 7.86 (s, 1H, H-3), 7.34 (d, 2H, J 2 Hz,
Ph), 7.31 (s, 1H, H-8), 7.04 (dd, 1H, J1 2, J2 9 Hz, H-6), 4.16
(s, 2H, NH2), 2.43 (s, 3H, 2 CH3); 13C NMR (DMSO-d6)
d 156.9 (C-2), 150.9 (C-8a), 148.2 (C-7), 139.8, 136.0
(2 C-Ph), 134.5 (q, 2J 31 Hz, C-4), 129.5, 127.2 (4 C-Ph),
124.8 (C-5), 123.7 (q, 1J 275 Hz, CF3), 119.4 (C-6), 115.2
(C-4a), 112.1 (q, 3J 5 Hz, C-3), 110.0 (C-8), 21.2 (CH3);
GC-MS (EI, 70 eV, m/z) 302 (M+, 100), 233 (23), 69 (10%);
Anal. calcd. for C17H13F3N2 (302.10):C, 67.54; H, 4.33; N,
9.27%. Found: C, 67.14; H, 4.19; N, 8.90%.
4,8-bis(Trifluoromethyl)-2,10-di(4-nitrophenyl)-
1,7-phenanthroline (3i)
Yellow solid (0.29 g, 23% yield); mp 249-251 °C;
1H NMR (CDCl3) d 8.37 (dd, 4H, J1 2, J2 8 Hz, Ph), 8.12
(dd, 4H, J1 2, J2 8 Hz, Ph), 7.97 (dq, 1H, J1 2, J2 8 Hz,
H-5), 7.90 (s, 1H, H-3), 7.37 (s, 1H, H-9), 7.13 (dd, 1H,
J1 2, J2 8 Hz, H-6); 13C NMR (CDCl3) d 155.5 (C-10),
2
153.9 (C-2), 152.0 (C-10b), 150.4 (q, J 34 Hz, C-8),

1436
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
4-Trifluoromethyl-2-(4-methoxylphenyl)-7-aminoquinoline
(4e)
(dq, 1H, J1 2, J2 8 Hz, H-5), 7.83 (s, 1H, H-3), 7.65 (dd,
2H, J1 2, J2 8 Hz, Ph), 7.33 (d, 1H, J 2 Hz, H-8), 7.07
(dd, 1H, J1 2, J2 8 Hz, H-6), 4.20 (s, 2H, NH2); 13C NMR
(DMSO-d6) d 154.1 (C-2), 150.9 (C-8a), 150.6 (C-7),
Brown solid (0.13 g, 20% yield); mp 173-175 °C;
1H NMR (CDCl3) d 8.22 (dd, 2H, J1 2, J2 8 Hz, Ph), 7.89
(s, 1H, H-3), 7.80 (dq, 1H, J1 2, J2 9 Hz, H-5), 7.21 (s, 1H,
H-8), 7.18 (dd, 1H, J1 2, J2 9 Hz, H-6), 7.10 (dd, 2H, J1 2, J2
8 Hz, Ph), 5.98 (s, 2H, NH2), 3.85 (s, 3H, OCH3); 13C NMR
(DMSO-d6) d 160.5 (C-2), 154.9 (C-8a), 150.6 (C-7), 132.8
(q, 2J 31 Hz, C-4), 130.4, 128.2 (3 C-Ph), 123.6 (q, 1J 275,
CF3), 123.4 (q, 4J 2 Hz, C-5), 119.7 (C-6), 113.9 (3 C-Ph),
2
137.1 (C-Ph), 133.2 (q, J 31 Hz, C-4), 131.4, 128.8,
1
123.5 (5 C-Ph), 123.6 (q, J 275 Hz, CF3), 123.2 (C-5),
120.6 (C-6), 113.0 (C-4a), 109.8 (q, 3J 5 Hz, C-3), 107.1
(C-8); GC-MS (EI, 70 eV, m/z) 366 (M+, 100), 347 (6),
297 (14), 280 (4), 69 (5%); Anal. calcd. for C16H10BrF3N2
(366.00): C, 52.34; H, 2.75; N, 7.63%. Found: C, 52.40;
H, 2.71; N, 7.58%.
3
112.5 (4a), 109.6 (q, J 5 Hz, C-3), 107.5 (C-8), 54.9 (2
OCH3); GC-MS (EI, 70 eV, m/z) 318 (M+, 100), 233 (5), 249
(29), 69(12%);Anal. calcd. forC17H13F3N2O(318.10):64.15;
H, 4.12; N, 8.80%. Found: C, 63.89; H, 3.98; N, 8.80%.
4-Trifluoromethyl-2-(4-nitrophenyl)-7-aminoquinoline (4i)
Beige solid (0.14 g, 21% yield); mp 199-201 °C;
1H NMR (CDCl3) d 7.98 (d, 2H, J 8 Hz, Ph), 7.87 (d, 1H,
J 8 Hz, H-5), 7.80 (s, 1H, H-3), 7.30 (d, 1H, J 2 Hz, H-8),
7.00 (d, 1H, J 2 Hz, H-6), 6.79 (d, 2H, J 8 Hz, Ph), 5.34 (s,
2H,NH2);13CNMR(DMSO-d6)d153.3(C-2),151.4(C-8a),
4-Trifluoromethyl-2-(4-fluorophenyl)-7-aminoquinoline
(4f)
Yellow solid (0.27 g, 45% yield); mp 191-193 °C;
1H NMR (DMSO-d6) d 8.33-8.29 (m, 2H, Ph), 7.93 (s,
1H, H-3), 7.79 (dq, 1H, J1 2, J2 8 Hz, H-5), 7.37-7.33 (m,
2H, Ph), 7.21 (d, 1H, J 2 Hz, H-6), 7.18 (s, 1H, H-8), 6.10
(s, 2H, NH2); 13C NMR (DMSO-d6) d 163.1 (d,1J 248 Hz,
C-FPh), 154.3 (C-2), 150.8 (C-8a), 150.6 (C-7), 134.4 (d,
4J 3 Hz, C-FPh), 133.1 (q, 2J 31 Hz, C-4), 129.1 (d,3J 8 Hz,
2
150.8 (C-7), 148.1, 143.9 (2 C-Ph), 133.5 (q, J 31 Hz,
1
C-4), 128.4, 123.9 (4 C-Ph), 123.8 (q, J 275 Hz, CF3),
123.7 (C-5), 121.6 (C-6), 113.5 (C-4a), 110.7 (q, 3J 5 Hz,
C-3), 107.0 (C-8); 19 F NMR (CDCl3) d −61.23 (CF3-4);
GC-MS (EI, 70 eV, m/z) 333 (M+, 100), 314 (7), 264 (18),
248 (5), 69 (5%); Anal. calcd. for C16H10F3N3O2 (333.07):
C, 57.66; H, 3.02; N, 12.61%. Found: C, 57.52; H, 2.87;
N, 12.68%.
1
2 C-FPh), 123.5 (q, J 275 Hz, CF3), 123.4 (C-5), 120.3
2
(C-6), 115.3 (d, J 22 Hz, 2 C-FPh), 112.8 (C-4a), 109.9
(q, 3J 5 Hz, C-3), 107.2 (C-8); GC-MS (EI, 70 eV, m/z) 306
(M+, 100), 237 (22), 142 (8), 69 (16%); Anal. calcd. for
C16H10F4N2 (306.08): C, 62.75; H, 3.29; N, 9.15%. Found:
C, 62.58; H, 3.14; N, 9.01%.
4-Trifluoromethyl-2-(2-furyl)-7-aminoquinoline (4j)
To a stirred mixture of H3PO4 (0.8 mL) and P2O5 (1.2 g)
(PPA) at 90 °C, 2j (2 mmol) was added. Using an 10 cm
length glass adapter connecting the flask reaction and the
condenser, the mixture was stirred at 90 °C for 36 h. Then,
to the dark residue in the reaction flask was added 20 g of
crushed ice and ethyl acetate (20 mL). After stirring, the
7-aminoquinoline 4j was isolated when the aqueous phase
was extracted with ethyl acetate (6 × 20 mL) combined with
NaOH solution 40% (5 mL). The organic layer was washed
with distilled water (3 × 15 mL) and dried over sodium
sulfate. After filtration, the liquid phase was stirred and
heated in the presence of activated charcoal, filtered again
and the solvent removed under reduced pressure.
Yellowsolid(0.40g,73%yield),mp235-238°C;1HNMR
(DMSO-d6) d 7.96 (d, 1H, J 1 Hz, furyl), 7.79 (s, 1H, H-3),
7.75 (d, 1H, J 2 Hz, H-5), 7.43 (d, 1H, J 3 Hz, furyl), 7.19
(dd, 1H, J1 2, J2 9 Hz, H-6), 7.11 (d, 1H, J 2 Hz, H-8),
6.75-6.72 (m, 1H, J 2 Hz, furyl), 6.20 (s, 2H, NH2); 13C NMR
(DMSO-d6) d 152.5 (C-2), 151.2 (C-8a), 150.7 (C-7), 147.7,
145.0 (2 C-furyl), 133.0 (q, 2J 31 Hz, C-4), 123.9 (C-5), 123.6
(q, 1J 275 Hz, CF3), 120.3 (C-6), 112.7 (C-4a), 112.6, 110.9
(2 C-furyl), 108.8 (q, 3J 5 Hz, C-3), 106.8 (C-8); CG-MS (EI,
70 eV, m/z) 278 (M+, 100), 250 (11), 69 (4%);Anal. calcd. for
2-(4-Clorophenyl)-4-trifluoromethyl-7-aminoquinoline
(4g)
Yellow solid (0.22 g, 35% yield); mp 178-180 °C;
1H NMR (CDCl3) d 8.09 (dd, 2H, J1 2, J2 8 Hz, Ph), 7.93
(dq, 1H, J1 2, J2 8 Hz, H-5), 7.83 (s, 1H, H-3), 7.50 (dd, 2H,
J1 2, J2 8 Hz, Ph), 7.33 (d, 1H, J 2 Hz, H-8), 7.07 (dd, 1H,
J1 2, J2 9 Hz, H-6), 4.20 (s, 2H, NH2); 13C NMR (DMSO-d6)
d 154.2 (C-2), 151.1 (C-8a), 150.7 (C-7), 136.8, 134.6
(2 C-Ph), 133.3 (q, 2J 31 Hz, C-4), 128.8, 128.7 (4 C-Ph),
125.1 (C-5), 125.5 (q, 1J 275 Hz, CF3), 122.3 (C-6), 119.6
3
(C-4a), 110.0 (q, J 5 Hz, C-3), 107.1 (C-8); 19 F NMR
(CDCl3) d −61.30 (CF3-4); GC-MS (EI, 70 eV, m/z) 322
(M+, 100), 303 (4), 283 (4), 253 (4), 239 (16%);Anal. calcd.
for C16H10ClF3N2 (322.05): C, 59.55; H, 3.12; N, 8.68%.
Found: C, 59.63; H, 3.07; N, 8.61%.
2-(4-Bromophenyl)-4-trifluoromethyl-7-aminoquinoline
(4h)
Yellow solid (0.24 g, 33% yield); mp 177-179 °C;
1H NMR (CDCl3) d 8.03 (dd, 2H, J1 2, J2 8 Hz, Ph), 7.93

Vol. 22, No. 8, 2011
Bonacorso et al.
1437
C14H9F3N2O (278.07): C, 60.44; H, 3.26; N, 10,07%. Found:
C, 60.48; H, 3.25; N, 10.01%.
19. Ondi, L.; Lefebvre, O.; Schlosser, M.; Eur. J. Org. Chem. 2004,
3714.
20. Dubinina, G. G.; Furutachi, H.;Vicic, D. A.; J. Am. Chem. Soc.
2008, 130, 8600.
Supplementary Information
21. Denisova, A. B.; Sosnovskikh, V. Y.; Dehaen, W.; Toppet, S.;
Meervelt, L.V.;Bakulev,V.A.;J. FluorineChem. 2002, 115, 183.
22. Gerus, I. I.; Gorbunova, M. G.; Kukhar,V. P.; J. Fluorine Chem.
1994, 69, 195.
NMR spectra are available free of charge at
http://jbcs.sbq.org.br as PDF file.
Acknowledgements
23. Bonacorso, H. G.; Marques, L. M. L.; Zanatta, N.; Martins,
M. A. P.; Synth. Commun. 2002, 32, 3225.
The authors thank the Coordenação deAperfeiçoamento
de Pessoal de Nível Superior (CAPES) for fellowships and
the Conselho Nacional de Desenvolvimento Científico
e Tecnológico (CNPq) for financial support (Proc. No.
303.296/2008-9).
24. Bonacorso, H. G.; Wentz, A. P.; Bittencourt, S. T. R.; Marques,
L. M. L.; Zanatta, N.; Martins, M.A. P.; Synth. Commun. 2002,
32, 335.
25. Bonacorso, H. G.; Duarte, S. H. G.; Zanatta, N.; Martins,
M. A. P.; Synthesis 2002, 1037.
26. Bonacorso, H. G.; Drekener, R. L.; Rodrigues, I. R.; Vezzosi,
R. P.; Costa, M. B.; Martins, M. A. P.; Zanatta, N.; J. Fluorine
Chem. 2005, 126, 1384.
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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
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Submitted: November 17, 2010
Published online: March 31, 2011

J. Braz. Chem. Soc., Vol. 22, No. 8, S1-S31, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing
1,7-Phenanthrolines and Quinolines from Cyclocondensation Reaction of
N,N’-Bis(oxotrifluoroalkenyl)-1,3-Phenylenediamines
Helio G. Bonacorso,* Rosália Andrighetto, Nícolas Krüger,
Marcos A. P. Martins and Nilo Zanatta
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química,
Universidade Federal de Santa Maria, 97105-900 Santa Maria-RS, Brazil
NMR spectra of compounds
Figure S1. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2a).
*e-mail: heliogb@base.ufsm.br

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S2. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2a).
Figure S3. 19F NMR (376 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2a).

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Figure S4. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(5,5,5-trifluoro-4-oxo-2-penten-2-yl)-1,3-phenylenediamine (2b).
Figure S5. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(5,5,5-trifluoro-4-oxo-2-penten-2-yl)-1,3-phenylenediamine (2b).

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S6. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-phenyl-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2c).
Figure S7. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-phenyl-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2c).

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Figure S8. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-methylphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2d).
Figure S9. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-methylphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2d).

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S10. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-methoxyphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2e).
Figure S11. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-methoxyphenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2e).

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Figure S12. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-fluorophenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2f).
Figure S13. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[4-fluorophenyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2f).

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Figure S14. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-[1-[4-chlorophenyl]-4,4,4-trifluoro-3-oxo-1-buten-1-yl]-1,3-phenylenediamine (2g).
Figure S15. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-[1-[4-chlorophenyl]-4,4,4-trifluoro-3-oxo-1-buten-1-yl]-1,3-phenylenediamine (2g).

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Figure S16. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(1-[4-bromophenyl]-4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2h).
Figure S17. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(1-[4-bromophenyl]-4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2h).

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Figure S18. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-(4-nitrophenyl)-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2i).
Figure S19. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-(4-nitrophenyl)-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2i).

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Figure S20. 1H NMR (100 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[2-furyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2j).
Figure S21. 13C NMR (200 MHz, CDCl3) spectrum of (Z,Z)-N,N’-bis(4,4,4-trifluoro-1-[2-furyl]-3-oxo-1-buten-1-yl)-1,3-phenylenediamine (2j).

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S22. 1H NMR (100 MHz, CDCl3) spectrum of 2,8-bis(trifluoromethyl)-1,7-phenantroline (3a).
Figure S23. 13C NMR (200 MHz, CDCl3) spectrum of 2,8-bis(trifluoromethyl)-1,7-phenantroline (3a).

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Figure S24. 19F NMR (376 MHz, CDCl3) spectrum of 2,8-bis(trifluoromethyl)-1,7-phenantroline (3a).
Figure S25. 1H NMR (100 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(methyl)-1,7-phenanthroline (3b).

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S26. 13C NMR (200 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(methyl)-1,7-phenanthroline (3b).
Figure S27. 19F NMR (376 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(methyl)-1,7-phenanthroline (3b).

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Figure S28. 1H NMR (100 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(phenyl)-1,7-phenanthroline (3c).
Figure S29. 13C NMR (200 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(phenyl)-1,7-phenanthroline (3c).

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Simultaneous Regioselective Synthesis of Trifluoromethyl-Containing 1,7-Phenanthrolines and Quinolines J. Braz. Chem. Soc.
Figure S30. 19F NMR (376 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(phenyl)-1,7-phenanthroline (3c).
Figure S31. 1H NMR (100 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(4-methylphenyl)-1,7-phenanthroline (3d).

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Figure S32. 13C NMR (200 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(4-methylphenyl)-1,7-phenanthroline (3d).
Figure S33. 1H NMR (100 MHz, CDCl3) spectrum of 4,8-bis(trifluoromethyl)-2,10-di(4-methoxyphenyl)-1,7-phenanthroline (3e).