The unexpected cyclization routes of N,N′-bis(oxotrifluoroalkenyl)-1, 3-phenylenediamines in polyphosphoric acid medium

Article abstract of DOI:10.1016/j.tetlet.2010.05.041

The unexpected results of the cyclization reactions of N,N′- bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C₆H ₄-(NHCR=CHC(O)CF₃)₂], where R = H, Me, and Ph, in a strongly acidic medium (PPA), allowing the synthesis of new trifluoromethylated heterocycles containing the 1,7-phenanthroline nucleus in 32-40% yields and 7-aminoquinolines (38-40% yields), is reported. The bis-enaminoketone intermediates were easily isolated from the reactions of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones with 1,3-phenylenediamine in ethanol under mild conditions (68-86% yields).

Full text of DOI:10.1016/j.tetlet.2010.05.041

Tetrahedron Letters 51 (2010) 3752–3755
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The unexpected cyclization routes of N,N0-bis(oxotrifluoroalkenyl)-
1,3-phenylenediamines in polyphosphoric acid medium
*
Helio G. Bonacorso , Rosália Andrighetto, Nilo Zanatta, Marcos A. P. Martins
Núcleo de Química de Heterociclos, NUQUIMHE, Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
The unexpected results of the cyclization reactions of N,N0-bis(oxotrifluoroalkenyl)-1,3-phenylenediam-
ines [1,3-C6H4-(NHCR@CHC(O)CF3)2], where R = H, Me, and Ph, in a strongly acidic medium (PPA), allow-
ing the synthesis of new trifluoromethylated heterocycles containing the 1,7-phenanthroline nucleus in
32–40% yields and 7-aminoquinolines (38–40% yields), is reported. The bis-enaminoketone intermediates
were easily isolated from the reactions of 4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones with 1,3-
phenylenediamine in ethanol under mild conditions (68–86% yields).
Article history:
Received 22 March 2010
Revised 10 May 2010
Accepted 11 May 2010
Available online 15 May 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Phenanthrolines have been prepared from aminoquinolines1 or
phenylenediamines.2 From a synthetic point of view, those ob-
tained from phenylenediamines are of particular advantage since
both rings can be constructed simultaneously.2 In addition, it has
been observed that the replacement of a hydrogen or halogen atom
or of an amino, alkoxy, or alkyl group by a CF3 group can modulate
the physical, chemical, and biological properties.3 The attachment
of a trifluoromethyl entity to a carbon skeleton can be accom-
plished in several ways.3,4 One the most satisfactory methods of
introducing a CF3 group into heterocycles is via the trifluoromethy-
lated building block approach.5–11
Similarly, enaminones like 2 are versatile readily obtainable re-
agents and their chemistry has received considerable attention in
recent years.12–18 These enamino-carbonyl compounds represent
versatile synthetic precursors that combine the ambident nucleo-
philicity of enamines with the ambident electrophilicity of enones
presenting three nucleophilic and two electrophilic sites.
Herein, we present a general method for the synthesis of
enaminones 2a–c from the reaction of enones 1a–c with 1,3-phenyl-
enediamine (Scheme 1), as well as a new application of the method
previously described by us for the preparation of some trifluoro-
methyl-substituted benzo[h]quinolines,13 dihydrobenzo[c]acri-
dines,14 cycloalka[b]quinolines,15 and 1,2,3,4-tetrahydroacridi-
nes,16 now applied successfully in the synthesis of bis-trifluorome-
thylated 1,7-phenanthrolines (3a–c) and 7-aminoquinolines
(4b–c). We also report two interesting intramolecular cyclization
routes when enaminones 2a–c were heated in polyphosphoric acid
medium.
4-alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones (1a–c) with
1,3-phenylenediamine in a molar ratio of 2:1, respectively, when
the reactions were carried out in ethanol at 40 °C for 2 h.26
4-Alkoxy-4-alkyl(aryl)-1,1,1-trifluoroalk-3-en-2-ones
(1a–c)
are readily available CCC synthetic blocks and 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) with trifluoroacetic anhydride, respec-
tively, in the presence of pyridine, as described in the literature.19
The structures of compounds 2a–c were easily established on
the basis of 1H and 13C NMR spectroscopy.27 In order to obtain
structural information about the configuration of the compounds
1
2a–c we have performed an H NMR study on N,N0-bis(3-oxo-
4,4,4-trifluorobut-1-en-1-yl)-1,3-phenylenediamine (2a). The 1H
NMR spectrum of 2a in CDCl3 showed a cis coupling constant for
the vicinal olefin protons with J ꢀ8 Hz, which is consistent with
a Z-configuration as the E- and Z-forms can be easily distinguished
by their 1H NMR spectra because the N–H signals of the E-form (in
4– 8 ppm) appear at a much higher field than those of the Z-form
(in 9–13 ppm), indicating the presence of an intramolecular hydro-
gen bonding in the latter.20 The 1H NMR chemical shift of the
R
O
R
O
O
OEt(Me)
R
i
N
H
N
H
F3C
F3C
CF3
Scheme 1 outlines the synthesis of a new series of three
trifluoromethylated 1,3-phenylene-bis-enaminone intermediates
(2a–c) isolated in satisfactory yield (68–86%) from the reaction of
1a-c
2a-c
1-2
a
b
c
R
H
Me Ph
* Corresponding author. Tel.: +55 553220 8867; fax: +55 5532208031.
E-mail address: heliogb@base.ufsm.br (H.G. Bonacorso).
Scheme 1. Reagents and conditions: (i) = m-(NH2)2C6H4 (0.5 equiv), ethanol, 40 °C,
2 h (68–86%).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.041

H. G. Bonacorso et al. / Tetrahedron Letters 51 (2010) 3752–3755
3753
enamino hydrogens (NH) for 2a–c were observed on average at
12.18 ppm, allowing one to assume that the enaminones 2a–c exist
in the Z,Z-configuration in CDCl3, which is stabilized by an intra-
molecular hydrogen bond (N–Hꢁ ꢁ ꢁO@C) in each enaminone moiety.
In a second reaction step, the acyclic compounds 2a–c were
subjected to reactions carried out in the presence of a strongly
acidic medium (polyphosphoric acid, PPA), in the absence of sol-
vent. For all reactions, initially, PPA (P2O5 + H3PO4) was prepared
at 90 °C and the compounds 2a–c were added to the acid mixture.
The cyclization of 2a–c showed that the best results were at 165 °C
for 36 h, affording the corresponding angular new series of bis-tri-
fluoromethyl-substituted 1,7-phenanthrolines (3a–c) in 32–40%
yields and 7-aminoquinolines (4b–c) in 38–40% yields (Schemes
2 and 3).28
isomer. 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 (CF3,
2
1JCF = 275 Hz) and d 134.8 ppm (C4, JCF = 31 Hz), respectively. In
some cases, as described by the same authors, the reactions
resulted in mixtures of 2- and 4-CF3 quinolines.
Schlosser et al.17,18 have investigated in details the synthesis of
2- and 4-(trifluoromethyl)quinolines and quinolinones and deter-
mined that some perfluoroalkyl-substituted 3-aminoenones when
heated in the presence of phosphoryl chloride cleaved hydrolyti-
cally setting free the substituted anilines and the 1,3-dicarbonyl
compounds. A proved recombination of these subunits furnished
unexpected 2-(CF2)nCF3-quinolines. We think that the mechanism
suggested by Schlosser may also explain the unexpected findings
of our work.
The structures of 3a–c were established on the basis of 1H, 13C
NMR spectroscopy29 and the literature data for similar com-
pounds.13–16,21 According to the results of the presented synthesis,
we found two different mechanisms involved to obtain the phen-
anthrolines 3a–c.
Surprisingly, these two cyclization routes that so far have only
been observed separately in some molecules12,17,18,21,22,24 here oc-
curred for the symmetrical enaminones 2b–c (R – H) without any
isomeric mixture, but also with the isolation of 7-aminoquinolines
4b–c (Scheme 3).
From the analysis of NMR data we observed that one ring clo-
sure 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) and in the second
ring 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–c).
Compounds 3 were separated from the reaction mixture by a sub-
limation process during the heating of the pure enaminone precur-
sors 2b–c, in PPA medium.
The 2-alkyl(aryl/heteroaryl)-7-amino-4-(trifluoromethyl) quin-
olines (4b–c) were obtained in 38–40% yields, as by-products, from
the reported cyclization reactions and were isolated by recrystalli-
zation after the work-up of residual reaction mixtures according to
the procedure described.28 The isolation of 4b–c suggests also that
a hydrolysis reaction occurred in 2b–c, and the expected recombi-
nation of the precursors to allow the synthesis of 3b–c, due to the
high reaction temperature, did not occur totally and probably be-
cause the dicarbonyl compounds evaporated from the hot reaction
mixtures.
The structure pattern of the compound 3a is different from that
of 3b–c,29 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 de-
scribed in the literature for a single cyclocondensation reaction,
which allowed the isolation of 2-trifluoromethyl-substituted quin-
olines12,17,18,21–24 and benzo[h]quinolines.23,24
Gerus12 employed the b-ethoxyvinyl trifluoromethyl ketone 1a
in reaction with aniline to promote the synthesis of the respective
quinoline, obtaining the 2-(trifluoromethyl) quinoline isomer, in
30% yield, as the only product by heating the respective enaminone
in acidic medium (PPA).
Linderman and Kirollos21 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 (CF3,
2
1JCF = 275 Hz) and at d 148.5 ppm (C2, JCF = 34 Hz). In the same
Letter, another intramolecular cyclization route was also described,
which allowed the synthesis of the 4-(trifluoromethyl)quinoline
The structures of 4b–c were established on the basis of 1H and
13C NMR spectroscopy30 and the literature data for similar
compounds.21,22,24,25 It is interesting that according to the results
observed for cyclization of N,N0-bis[3-oxo-4,4,4-trifluorobut-1-en-
1-yl]-1,3-phenylenediamine (2a) in PPA the respective 7-amino-
4-(trifluoromethyl)quinoline (4a) or any other quinoline analog
was not isolated or observed by NMR experiments.
CF3
N
N
H
N
H
i
The possible formation of the 2,10-bis(trifluoromethyl)-1,7-
phenanthroline isomer was also excluded because the 5-amino-
4-(trifluoromethyl)quinolines were not detected in the cyclization
reactions from 2b–c. The possible formation of the 4,10-bis(trifluo-
F3C
O
O
CF3
F3C
N
2a
3a
Scheme 2. Reagents and conditions: (i) = PPA, 165 °C, 36 h (32%).
R
CF3
R
N
F3C
CF3
i
CF3
i
2b-c
R
R
NH2
R
N
N
N
F3C
N
5
3b-c (38 - 40 %)
4b-c (38 - 40 %)
b
c
2-5
R
Me Ph
Scheme 3. Reagents and conditions: (i) = PPA, 165 °C, 36 h.

3754
H. G. Bonacorso et al. / Tetrahedron Letters 51 (2010) 3752–3755
15. Bonacorso, H. G.; Moraes, T. S.; Zanatta, N.; Martins, M. A. P.; Flores, A. F. C.
ARKIVOC 2008, xvi, 75.
16. Bonacorso, H. G.; Moraes, T. S.; Zanatta, N.; Martins, M. A. P. Synth. Commun.
2009, 39, 3677.
romethyl)-1,7-phenanthroline isomer was also excluded because
the CF-coupling should be present on the NMR spectra as one quar-
tet signal for the CF3 group and two identical quartets for C-4 and
C-10 in the narrow range of d147–150 ppm and no quartet signals
should be expected in the region of d 134–135 ppm.
17. Schlosser, M.; Keller, H.; Sumida, S.-I.; Yang, J. Tetrahedron Lett. 1997, 38, 8523.
18. Marull, M.; Lefebvre, O.; Schlosser, M. Eur. J. Org. Chem. 2004, 54.
19. (a) Hojo, M.; Masuda, R.; Kokuryo, Y.; Shioda, H.; Matsuo, S. Chem. Lett. 1976,
499; (b) Effenberger, F.; Maier, R.; Schonwalder, K. H.; Ziegler, T. Chem. Ber.
1982, 115, 2766; (c) Effenberger, F.; Schonwalder, K. H. Chem. Ber. 1984, 117,
3270; (d) Kamitori, Y.; Hojo, M.; Masuda, R.; Fujitani, T.; Kobuchi, T.; Nishigaki,
T. Synthesis 1986, 340; (e) Hojo, M.; Masuda, R.; Okada, E. Synthesis 1986, 1013;
(f) Hojo, M.; Masuda, R.; Sakaguchi, S.; Takagawa, M. Synthesis 1986, 1016; (g)
Colla, A.; Martins, M. A. P.; Clar, G.; Krimmer, S.; Fischer, P. Synthesis 1991, 483;
(h) Martins, M. A. P.; Emmerich, D. J.; Pereira, C. M. P.; Cunico, W.; Rossato, M.;
Zanatta, N.; Bonacorso, H. G. Tetrahedron Lett. 2004, 45, 4935.
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 pyrido[g]quinolines (5), as reported
in the literature (Scheme 3).23 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 (pyr-
ido[g]quinoline). In our case, all spectroscopic data were consistent
with the angular proposed structures for phenanthrolines 3a–c,
which are preferably obtained according to the literature.2
Depending on the structure of the N,N0-bis(oxotrifluoroalkenyl)-
1,3-phenylenediamines (2), 2,8-bis-(trifluoromethyl)-1,7-phenan-
throline or a mixture of separable 4,8-bis-(trifluoromethyl)-1,
7-phenanthrolines and 4-(trifluoromethyl)-7-aminoquinolines
was obtained. The initial results reported here showed an interest-
ing chemical behavior for the mechanism of cyclization of these
new enamino ketones 2, showing selective routes of ring closure
including direct cyclocondensations, hydrolyses, and recombina-
tions, which furnished new fused bis-(trifluoromethyl)-diaz-
atricycles.
20. Zhuo, J.-C. Magn. Reson. Chem. 1997, 35, 21.
21. Linderman, R. J.; Kirollos, K. S. Tetrahedron Lett. 1990, 31, 2689.
22. Keller, H.; Schlosser, M. Tetrahedron 1996, 52, 4637.
23. Riedel, D.; Feindt, A.; Pulst, M. J. Prakt. Chem. 1995, 337, 34.
24. Sloop, J. C.; Bumgardner, C. L.; Loehle, W. D. J. Fluorine Chem. 2002, 118, 135.
25. Panda, K.; Siddiqui, I.; Mahata, P. K.; Junjappa, H. Synlett 2004, 449.
26. Synthesis of N,N’-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines (2a–c).
General procedure: To a stirred solution of 1,3-phenylenediamine (0.54 g,
5 mmol) in ethanol (10 mL), 1a–c (10 mmol) was added at room temperature.
The mixture was stirred for 2 h at 40 °C. After the end of the reaction (TLC), the
resulting solid products 2a–c 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 gathered and recrystallized from chloroform (68–86% yields).
27. Compounds 2a–c were characterized by 1H and 13C NMR. Spectral data of
compound 2a: 1H NMR (200 MHz, CDCl3): d = 11.74 (d, J = 12 Hz, 2H, NH), 7.63
(dd, J1 = 8, J2 = 12 Hz, 2H, H-1), 7.41 (t, J = 8 Hz, 1H, H-9), 6.95 (dd, J1 = 2,
J2 = 8 Hz, 2H, H-8, H-10), 6.86 (t, J = 2 Hz, 1H, H-6), 5.71 (d, J = 8 Hz, 2H, H-2).
13C NMR (100 MHz, CDCl3): d = 179.3 (q, 2J = 34 Hz, 2 C-3), 149.3 (2 C-1), 140.3
(2C, C-5, C-7), 131.3 (C-6), 116.5 (q, 1J = 289 Hz, 2CF3), 113.8 (2C, C-8, C-10),
105.7 (C-9), 90.3 (2 C-2). GC–MS (EI, 70 eV): m/z (%) = 352 (M+, 100), 283 (55),
213 (23), 185 (33), 107 (24), 263 (11), 69 (5). 19F NMR (376 MHz, CDCl3):
d = ꢂ75.35 (2-CF3). 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. Melting points and yields of new
compounds 2: Compound [mp (°C), yield (%)]: 2a [171–173, 68]; 2b [126–
128 °C, 86]; 2c [190–192, 80].
28. Synthesis of 2,8-bis(trifluoromethyl)-1,7-phenantroline (3a) and 2,10-
substituted-4,8-bis(trifluoromethyl)-1,7-phenanthrolines (3b–c) and 7-
aminoquinolines (4b–c). General procedure: To a stirred mixture of H3PO4
(2 mL) and P2O5 (3 g) (PPA) at 90°, 2a–c (2 mmol) were added. Using a 10 cm
length glass adapter connecting the reaction flask and the condenser, the
mixture was stirred for 36 h at 165 °C. After this time, the sublimated products
3a–c 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 (32–40% yields). To the
dark residue remainder in the reaction flask were added 20 g of crushed ice and
ethyl acetate (20 mL). After stirring, the 7-aminoquinolines (4b–c) were
isolated when the aqueous phase was extracted with ethyl acetate
(6 ꢃ 20 mL) combined with NaOH solution 40% (5 mL). The organic layer was
washed with distilled water (3 ꢃ 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–c) were recrystallized from a mixture of ethyl
acetate/hexane (3:1 v/v) (38–40% yields).
Unless otherwise indicated all common reagents and solvents
were used as obtained from commercial suppliers without further
purification. The melting points were determined using 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) spectrome-
ter, 5 mm sample tubes, 298 K, digital resolution 0.01 ppm, in
CDCl3 for 1, 2, 3a–c and in DMSO-d6 for 4b–c, using TMS as internal
reference (1H and 13C) or fluorobenzene as external reference (19F).
Mass spectra were registered in a HP 6890 GC connected to a HP
5973 MSD and interfaced by a Pentium PC. The GC was equipped
with a split–splitless injector, autosampler, cross-linked HP-5 cap-
illary column (30 m, 0.32 mm of internal diameter), and helium
was used as the carrier gas. The CHN elemental analyses were per-
formed on a Perkin–Elmer 2400 CHN elemental analyzer (São Pau-
lo University, USP/Brazil).
Acknowledgment
The authors thank for the financial support from Conselho Nac-
ional de Desenvolvimento Científico – CNPq. (Proc. No. 303.296/
2008-9).
29. Compounds 3a–c were characterized by 1H and 13C NMR. Spectral data of
compound 3a: 1H NMR (200 MHz, CDCl3): d = 9.79 (d, J = 9 Hz, 1H, H-10), 8.48
(d, J = 8 Hz, 1H, H-4), 8.27 (d, J = 9 Hz, 1H, H-3), 8.11 (d, J = 9 Hz, 1H, H-9), 8.03
(d, J = 8 Hz, 1H, H-5), 8.01 (d, J = 8 Hz, 1H, H-6). 13C NMR (100 MHz, 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 (C-
4a), 121.5 (q, 1J = 275 Hz, CF3), 119.2 (C-3), 118.4 (C-9). 19F NMR (376 MHz,
CDCl3): d = ꢂ67.12, ꢂ67.26 (CF3-2, CF3-8). 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.
Spectral data of compound 3b: 1H NMR (200 MHz, CDCl3): d = 8.23 (dq, J1 = 2,
J2 = 8 Hz, 1H, H-5), 8.15 (d, J = 8 Hz, 1H, 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 (100 MHz, 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 (376 MHz, CDCl3):
d = ꢂ60.46 (CF3-4), ꢂ67.36 (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. Melting points and
yields of new compounds 3: Compound [mp (°C), yield (%)]: 3a [131–133, 32];
3b [147–149 °C, 38]; 3c [226–228, 40].
References and notes
1. Liska, K. J. J. Med. Chem. 1972, 15, 1177.
2. Graf, G. I.; Hastreiter, D.; da Silva, L. E.; Rebelo, R. A.; Montalbanb, A. G.;
McKillop, A. Tetrahedron 2002, 58, 9095.
3. Schlosser, M. Angew. Chem., Int. Ed. 2006, 45, 5432.
4. Schlosser, M. Synlett 2007, 3096.
5. Bonacorso, H. B.; Bittencourt, S. R. T.; Lourega, R. V.; Flores, A. F. C.; Zanatta, N.;
Martins, M. A. P. Synthesis 2000, 1431.
6. Cottet, F.; Marull, M.; Lefebvre, O.; Schlosser, M. Eur. J. Org. Chem. 2003, 1559.
7. Marull, M.; Schlosser, M. Eur. J. Org. Chem. 2003, 1576.
8. Ondi, L.; Lefebvre, O.; Schlosser, M. Eur. J. Org. Chem. 2004, 3714.
9. Dubinina, G. G.; Furutachi, H.; Vicic, D. A. J. Am. Chem. Soc. 2008, 130, 8600.
10. Martins, M. A. P.; Machado, P.; Rosa, F. A.; Cunico, W.; Bonacorso, H. G.;
Zanatta, N. Mini-Rev. Org. Chem. 2008, 5, 53.
11. Bonacorso, H. G.; Porte, L. M. F.; Cechinel, C. A.; Paim, G. R.; Deon, E. D.; Zanatta,
N.; Martins, M. A. P. Tetrahedron Lett. 2009, 50, 1392.
12. Gerus, I. I.; Gorbunova, M. G.; Kukhar, V. P. J. Fluorine Chem. 1994, 69, 195.
13. Bonacorso, H. B.; Duarte, S. H. G.; Zanatta, N.; Martins, M. A. P. Synthesis 2002,
1037.
14. 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.
30. Compounds 4b–c were characterized by 1H and 13C NMR. Spectral data of
compound 4b: 1H NMR (200 MHz, CDCl3): d = 7.87 (dq, J1 = 2, J2 = 9 Hz, 1H, H-

H. G. Bonacorso et al. / Tetrahedron Letters 51 (2010) 3752–3755
3755
5), 7.30 (s, 1H, H-3), 7.21 (d, J = 2 Hz, 1H, H-8), 7.02 (dd, J1 = 2, J2 = 9 Hz, 1H, H-
6), 4.18 (s, 2H, NH), 2.72 (s, 3H, 2 CH3). 13C NMR (100 MHz, 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 = ꢂ61.25 (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. Melting points and yields of new compounds 4: Compound
[mp (°C), yield (%)]: 4b [174–176, 40]; 4c [139–141 °C, 38].