New regiospecific synthesis of 2-trifluoromethyl-1,5 diazapentadiene compounds and of 2-trifluoromethylquinolines, their cyclization products

Article abstract of DOI:10.1021/jo050586d

2-Trifluoromethylquinolines 5 are synthesized in high yields using a perfluoroalkylated gemiodoacetoxy derivative 3 and arylamines 4. The intermediate of this reaction, 2-trifluoromethyl-1,5-diazapentadiene compound 6, was isolated. The procedures are eas

Full text of DOI:10.1021/jo050586d

New Regiospecific Synthesis of 2-Trifluoromethyl-1,5
Diazapentadiene Compounds and of 2-Trifluoromethylquinolines,
Their Cyclization Products
Salem El Kharrat, Myriem Skander, Abdelkader Dahmani, Philippe Laurent,* and
Hubert Blancou
Laboratoire de Chimie Organique Organization Mole´culaire, Evolution et Mate´riaux Fluore´s, Universite´
Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 05, France
philippe.laurent@univ-montp2.fr
Received March 23, 2005
2-Trifluoromethylquinolines 5 are synthesized in high yields using a perfluoroalkylated gem-
iodoacetoxy derivative 3 and arylamines 4. The intermediate of this reaction, 2-trifluoromethyl-
1,5-diazapentadiene compound 6, was isolated. The procedures are easy, and yields are in general
high. This sequence represents a valuable new synthesis of substituted 2-trifluoromethylquinolines
and of 2-trifluoromethyl-diazapentadienes (vinamidine compounds).
Introduction
The synthesis of various substituted quinolines has
been largely described in the literature through many
different strategies.6,7a,b For example, the preparation of
quinolines by Lewis acid catalyzed cyclization of 1,5-
diaryl-1,5-diazapentadienes salts has been known since
1923.8 These compounds were prepared by the action of
primary arylamines on â-chlorovinylaldehydes at room
temperature.9,10 Some diazapentadienes salts are able of
undergoing intramolecular cyclization when heated un-
der reflux in acetic acid or in alcohols of similar boiling
point and are converted in excellent yields into quino-
lines.11 The mechanism under these conditions has been
rationalized as an electrocyclic ring closure with elimina-
The last years have shown a tremendous increase of
new organofluorine compounds due to the unique proper-
ties exhibited by such substrates.1,2 Among them, triflu-
oromethyl-substituted molecules constitute a particular
class because of specific properties such as the high
lipophilicity and the resistance to enzyme degradation
brought by the CF3 group.3,4 Quinoline moieties are
structural elements of many drugs, as for example anti-
malarial agents. Since the classical anti-malarial mol-
ecules are encountering increased drug resistance, con-
siderable efforts have been directed toward the synthesis
of new fluorinated quinolines that can provide improved
anti-parasitic activity.5
(6) Kouznetsov, V. V.; Mendez, L. Y.; Gomez, C. M. Curr. Org. Chem.
2005, 9 (2), 141-161.
* To whom correspondence should be addressed. Tel: (33) 467144678.
Fax: (33) 467631046.
(1) Schofield, H. J. Fluorine Chem. 1999, 100, 7-11.
(7) (a) Chambers, R. D.; Holling, D.; Sandford, G.; Puschmann, H.;
Howard, J. A. K. J. Fluorine Chem. 2002, 117, 99-101. Chambers, R.
D.; Holling, D.; Sandford, G.; Batsanov, A. S.; Howard, J. A. K. J.
Fluorine Chem. 2004, 125, 661-671. (b) Bonnet, V.; Mongin, F.;
Trecourt, F.; Queguiner, G.; Knochel, P. Tetrahedron 2002, 58, 4429-
4438.
(2) Gross, U.; Ru¨diger, S. In Organo-Fluorine Compounds; Baasner,
B., Hagemann, H., Tatlow, J. C., Eds.; Houben-Weyl Methods of
Organic Chemistry; Thieme: Stuttgart, 1999; Vol. E10a, pp 18-26.
(3) Elliott A. J. In Chemistry of Organic Fluorine Compounds II, A
Critical Review; Hudlick M., Pavlath, A. E., Eds.; ACS Monograph 187,
American Chemical Society: Washington, DC, 1995; pp 1119-1125.
(4) Smart B. E. J. Fluorine Chem. 2001, 109, 3-11.
(8) Konig, W. Ber. 1923, 56, 1853.
(9) Julia, M. Ann. Chim. (France) 1950, 595.
(10) Gagan, J. M.; Lloyd, D. J. Chem. Soc., Chem. Commun. 1967,
1043.
(5) Ismail F. M. J. Fluorine Chem. 2002, 118, 27-33.
(11) Acheson, R. M.; Bolton, R. G. Tetrahedron Lett. 1973, 2827.
10.1021/jo050586d CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/13/2005
J. Org. Chem. 2005, 70, 8327-8331
8327

El Kharrat et al.
SCHEME 1. Preparation of gem-Haloacetoxy
SCHEME 2. Reaction of Compound 3 with
Arylamines 4
Compounds 1 and Synthesis of Fulvenes 2a
a R1, R2 ) H, alkyl, aryl, etc.
TABLE 1. Products and Yields Obtained in the
tion.12 Similarly the thermolysis of diazapentadiene
analogues gives quinolines.13
Reaction of Compound 3 with Substituted Arylamines 4
R3 parent
aniline
T
[°C]
time convb
[h]
In this paper, we report the first evidence for the
synthesis and isolation of 2-trifluoromethyl-1,5-diaryl-
diazapentadienes derivatives 6 (Scheme 3). The corre-
sponding 2-trifluoromethylquinolines 5 were prepared
starting from 1-iodo-3,3,4,4,4-pentafluorobutyl acetate 3.
A mechanistic study is then detailed explaining the
regiospecificity of the reaction.
entry compd
methoda
[%]
1
5a
5b
5c
5d
5e
5f
H
A
40
12
12
12
12
72
24
24
24
24
36
36
>95
86
93
>95
0
85
88
85
93
83
80
2
o-Me
m-Me
p-Me
o-Cl
A
40
3
A
A
40
40
4
5
A or B
40-80
40
6
m-Cl
p-Cl
p-NO2
o-OH
m-COOH
p-CN
A
A
B
B
B
B
7
5g
5h
5i
40
gem-Haloacetoxy compounds14,15 1 or 3 are not com-
monly used in organic chemistry, probably because of
their instability. However, it must be remarked that such
compounds are in fact activated aldehydes. Between 1970
and 1980 many such compounds were synthesized in
order to prepare fulvenes 216,17 (Scheme 1).
8
80
9
80
10
11
5j
5k
80
80
a Method A: 5 mL of CH2Cl2/1 g of 3 refluxed at 40 °C. Method
B: 5 mL of CH2ClCH2Cl/1 g of 3 refluxed at 80 °C. b Conversion
determined by 19F NMR.
In the case of iodo-compound 3 the presence of a
fluorinated chain improves its stability and allows it to
be used in different reactions. Twelve years ago we found
that RFCH2CHIOAc 2 (RF ) CnF2n+1, n ) 2, 4, 6, ...) could
easily react with a lot of nucleophiles such as aliphatic
alcohols, carboxylic acids, and amides18 and gives, re-
spectively, ketals, acylals, and amidals. Even nitriles
react with 3 and give enamides RFCHdCH-NH-COR.19
first. The different conditions of the reactions and yields
are summarized in Table 1.
Surprisingly the presence of a strong electron-with-
drawing function in the benzene ring of the arylamines,
such as a nitro, carboxyl, or cyano group (R3 ) p-NO2,
m-COOH, p-CN), does not inhibit quinoline formation;
previous attempts to prepare such quinolines starting
with fluorinated22 or nonfluorinated23,24 materials were
unsuccessful. The same results were obtained with
moderately electronegative substituents such as chlorine
(R3 ) m-Cl and p-Cl), the corresponding quinolines are
obtained satisfactorily, except in the case of R3 ) o-Cl,
where no quinoline was formed under our standard
conditions.
Results and Mechanistic Study
1-Iodo-3,3,4,4,4-pentafluorobutyl acetate 3 was pre-
pared by literature procedures20,21 and was used in the
following syntheses without further purifications. After
several experiments between arylamines 4 and compound
3, we found that the optimum conditions of this reaction
are a 1:3 molar mixture of 3 and 4. Under such conditions
the quinolines 5 were the only major products in the
crude mixture (Scheme 2, Table 1).
As expected the electron-donating substituents (R3 )
p-Me, m-Me, o-Me) promote reaction and cyclize to give
in high yields the substituted quinolines.
In the case of meta-substituted arylamines (R3 ) m-Me,
m-Cl, m-COOH) the 19F NMR spectroscopy of each of the
reaction mixtures showed only one sharp singlet, which
had been assigned to the quinolines CF3. The NMR
coupling pattern of the corresponding quinolines showed
unambiguously in all cases that the substitution was only
in the 7-position; no formation of 5-substituted quinolines
was observed probably because of steric hindrance. Pre-
vious reports on the synthesis of quinolines describe that
3-substituted anilines lead to a mixture of products in
which the 7-substituted quinolines predominate;22 how-
ever, exceptions occur, for example, in the case of m-
nitroaniline, which gives mostly the 5-nitroquinoline.25-27
Recent works concerning the synthesis of 2-trifluorom-
ethylquinolines proposed a 3-trifluoromethylethanal as
The reaction was monitored by 19F NMR spectroscopy.
The terminal CF3 and the CF2 signals of compound 3
faded upon evolution of the reaction, and a new peak
appeared corresponding to the quinoline CF3 signal. At
the end of the reaction a simple workup procedure
afforded a brown liquid. The final products were easily
purified by silica gel chromatography because they eluted
(12) (a) Schroeder, G.; Luttke, W. Chem. Ber. 1972, 105, 2175. (b)
Palmer, M. H. J. Chem. Soc. 1962, 3645.
(13) (a) McNab, H.; Murray, E. A. J. Chem. Soc., Perkin Trans. 1
1988, 333. (b) McNab, H.; Murray, E. A. Arkivoc 2002, iii, 95.
(14) Brace, N. O. J. Fluorine Chem. 1999, 93, 1-25. Brace, N. O.
U.S. Patent 3,145,222, August, 1964.
(15) Krebs, A. Houben-Weyl. 1992, 14a/3, 85.
(16) Schenk, W. K.; Kibitz, R.; Neuenschwander, M. Helv. Chem.
Acta. 1975, 58, 1099.
(17) March, J. Advanced Organic Chemistry, 3rd ed.; Wiley: New
York, 1985; p 861.
(22) Keller, H.; Schlosser, M. Tetrahedron 1996, 52, 4637.
(23) Gagan, J. M. F.; Lloyd, D. J. Chem. Soc., Chem. Commun. 1967,
1043.
(18) Laurent, P.; Blancou, H.; Commeyras, A. Tetrahedron Lett.
1992, 2489.
(19) Laurent, P.; Tra Ahn, D.; Blancou, H.; Commeyras, A. J.
Fluorine Chem. 1999, 94, 139.
(24) Lloyd, D. Gagan, J. M. F. J. Chem. Soc. C 1970, 2488.
(25) Gagan, J. M. F.; Lloyd, D. J. Chem. Soc. C 1970, 2488.
(26) Bradford, L.; Elliott, T. J.; Rowe, F. M. J. Chem. Soc. 1947,
437.
(20) Brace, N. O. J. Org. Chem. 1962, 27, 3033.
(21) Laurent, P.; Blancou, H.; Commeyras, A. J. Fluorine Chem.
1993, 62, 161.
(27) Palmer, M. H. J. Chem. Soc. 1962, 3645.
8328 J. Org. Chem., Vol. 70, No. 21, 2005

Synthesis of 2-Trifluoromethyl-1,5 Diazapentadienes
SCHEME 3. Synthesis of
2-Trifluoromethyl-1,5-diazapentadienes 6
SCHEME 4. Mechanism of Formation of
Compounds 6a-j
TABLE 2. Yields Obtained of
2-Trifluoromethyl-1,5-diazapentadienes
R3 parent
aniline
T
[°C]
time
[h]
convd
[%]
entry
compd
methodc
1
2
6a
6b
6c
6d
6e
6f
H
C
C
C
C
C
C
C
D
D
D
20
20
20
20
20
20
20
40
40
40
2
3
93
83
o-Me
m-Me
p-Me
o-Cl
3
2
93
were not able to isolate this product. The highest yield
was achieved with R3 ) p-Me (>95% entry 4 Table 2).
The spectral data of new compounds 6a-j are ap-
propriate for their structures: the 1H NMR spectra were
assigned completely with comparison to literature.31,32 It
has been shown that the salts of 1,5-diaryl-diazapenta-
dienes exist as conjugated amino-imines, generally as a
mixture of the all-trans and cis-trans isomers with slow
exchange between them at room temperature.32 The
authors found that these salts exist in the all-trans form
in DMSO solutions.31 In our case, the pure compounds 6
were obtained as a powder and were immediately ana-
lyzed by NMR spectroscopy. All spectral analysis where
performed in deuterated DMSO, and the all-trans form
was always obtained in all cases. Furthermore the 19F
and 13C NMR spectras confirmed the structure of these
new products.
4
2
>95
70
5
4
6
m-Cl
p-Cl
p-NO2
m-COOH
p-CN
4
85
7
6g
6h
6i
4
85
8
1/2
1
68
9
70
10
6j
1/2
70
c Method C: 10 mL of CH2Cl2/1 g of 3 stirred at room temper-
ature. Method D: 10 mL of CH2Cl2/1 g of 3 refluxed at 40 °C.
d Conversion determined by 19F NMR.
intermediate.28 Therefore we choose to study the reactiv-
ity of compound 3 toward arylamines in the aim of
clarifying the mechanism of this reaction.29,30
Treatment of compound 3 with arylamines 4 in high
dilution conditions gives trifluoromethyl-1,5-diazapen-
tadienes 6 (Scheme 3, and Table 2). The highest yields
were obtained when using 1:2 molar equiv of 3 and
arylamines (R3 ) H, p-Me, m-Me, o-Me, p-Cl, m-Cl, o-Cl)
in dichloromethane as the reaction solvent and at room
temperature. Slightly decreased yields were observed in
the case of moderately electron-withdrawing groups R3
) o-Cl, m-Cl, p-Cl. When the same reaction conditions
were used at the higher temperature of 40 °C, lower
yields of diazapentadienes 6a-g with trace of quinolines
5a-g were obtained. In the case of high electron-
withdrawing substituents such as R3 ) p-NO2, m-COOH,
p-CN, when the reaction was performed at room tem-
perature very low yields of 6h-j were obtained. However,
by changing the reaction conditions we were able to
isolate in good yields the corresponding diazapentadienes
6h-j, but small amounts of quinolines 5 were also
obtained. In all cases complete consumption of the
starting substrate 3 was observed. The results are
summarized in Table 2.
This work is the first example of the synthesis and
isolation of substituted 2-trifluoromethyl-1,5-diazapen-
tadiene derivatives; only a few works on the synthesis of
related diazapentadienes are described in the litera-
ture.33-35
Monitoring the reaction of 3 with arylamines 4 by 19
F
NMR spectroscopy, we observed that the NMR signals
of compound 6 appeared quite quickly during the reaction
and after several hours disappeared to give a new peak
that was assigned to 5. This observation leads us to the
conclusion that compound 6 is the intermediate of the
synthesis of quinolines 5.
The formation of 6 can be explained by the attack of
the arylamine on the electrophilic center of 3 with
formation of an imine-enamine intermediate, which by
tautomeric equilibrium gives a conjugated iminium in-
termediate. Nucleophilic addition of arylamine and, in a
second step, elimination of hydrogen fluoride give 6
(Scheme 4).
Diazapentadienes 6 (R3 ) H, p-Me, m-Me, p-Cl, m-Cl)
were prepared in diluted media. Longer reaction times
or less diluted conditions were sometimes required
because of the additional steric requirements (R3 ) o-Me,
o-Cl) or because of the presence of electron-withdrawing
substituents (R3 ) p-NO2, p-CN, m-COOH). In the case
of R3 ) o-OH we detected the formation of the corre-
sponding diazapentadiene by mass spectrometry but
Theses 2-trifluoromethyl-1,5-diazapentadienes 6 are
produced as single stereochemically pure tautomers.
Furthermore the two nitrogen atoms in this imino-
enamine compound are not entirely equivalent, which
was confirmed by the signals in the NMR spectrum.31,32
(31) Richards, C. P.; Webb, G. A. Org. Magn. Reson. 1975, 7, 401.
(32) Honeybourne, C. L.; Webb, G. A. Spectrochim. Acta A 1969,
25, 1075.
(33) Lloyd, D.; McNab, H. Angew. Chem., Int. Ed. 1976, 15, 459.
(34) Schlosser, M.; Keller, H.; Sumida, S-I.; Yang, J. Tetrahedron
Lett. 1997, 49, 8523.
(35) Acheson, R. M.; Bolton, R. G.; Tetrahedron Lett. 1973, 2821.
Schroeder, G.; Luttke, W. Chem. Ber. 1972, 105, 2175.
(28) Wang, Q.-F.; Mao, Y.-Y.; Qin, C.-Y.; Zhu, S.-Z.; Hu, C.-M.
Monatsh. Chem. 2000, 131, 55.
(29) Dahmani, A.; Laurent, P.; Blancou, H. 16th International
Symposium of Fluorine Chemistry, Durham, U.K., 2000.
(30) El Kharrat, S.; Skander, M.; Laurent, P.; Blancou, H. 13th
European Symposium on Fluorine Chemistry, Bordeaux, July 2001.
J. Org. Chem, Vol. 70, No. 21, 2005 8329

El Kharrat et al.
SCHEME 5. Mechanism of CyclizAtion of
Compounds 6 in the Presence of Arylamines
SCHEME 6. Mechanism of the Acid-Catalyzed
Cyclization of Compounds 6a-j
very high yields (conversion of 6 to 5 >90%), except in
the case of 6e where no reaction was observed. The
corresponding quinolines were identified and compared
to those obtained previously. This reaction can be ex-
plained by an electrophilic aromatic cyclization mecha-
nism23,36 (Scheme 6).
The key step of this mechanism is the protonation of
the double bond of 6 and the formation of a cationic
intermediate. It seems that the electron-attractive effect
of the trifluoromethyl group is sufficient to induce elec-
trophilic ring closure to take place exclusively at the
-CHd group of the diazapentadienes 6 rather than at
the -CCF3 group, which would be highly disfavored. In
the same way an acid-catalyzed electrocyclic process that
occurs through the protonation of the nitrogen atom of
the imine function of compound 6 could be disfavored by
the adjacent CF3 group.
As we showed, the polyfluoro-gem-iodoacetylated com-
pounds 3 are very reactive toward aromatic amines. This
work constitutes another proof that they can react with
very weak nucleophiles.18,19 This reaction provides a new
general method for the preparation of trifluoromethyl-
diazapentadienes (vinamidines). Since these compounds
cyclize with complete regiospecificity, this reaction would
be potent in the preparation of substituted 2-trifluorom-
ethylquinolines.
To verify the assumption that the synthesis of quino-
lines 5 proceeds through intermediates of type 6 and to
reveal the reaction route as a whole, we decided to test
after its isolation the reactivity of 6 toward arylamines
4 and acetic acid, which are both present in the reaction
media.
We have carried out several experiments to test the
reactivity of compound 6a-j toward the corresponding
arylamines. First we heated diazapentadienes 6 in
dichloroethane at 80 °C, but no trace of the expected
quinolines was found. Then we checked the action of 1
molar equiv of arylamine 4 on 6 in refluxing dichlo-
romethane, and no reaction was observed. When dichlo-
roethane was used as a solvent at 80 °C in the presence
of 1 molar equiv of arylamine 4, quinolines 5 were formed
with good yields (conversion of 6 to 5 >90%). Except in
the case of R3 ) o-Cl, no reaction was observed and the
diazapentadiene 6e was recovered. The structure of the
resulting quinolines was unequivocally assigned on the
basis of a comparison of its physical data with those
obtained before.
We propose the following mechanism for this reaction
(Scheme 5). The formation of quinolines 5 could be
explained by a push-pull cyclization mechanism assisted
by arylamines 4 in a first step and then loss of a proton,
resulting in regeneration of the aromatic rings (Scheme
5). There is complete regiospecificity of the ring closure
reaction. The trifluoromethyl-diazapentadienes 6 might
be expected to give both the 4-trifluoromethylquinolines
and the 2-trifluoromethylquinolines, but in fact in the
absence of tautomeric equilibrium the pure tautomer 6
cyclizes in a total regiospecific manner and yields only
the 2-trifluoromethylquinolines 5.
Previous reports describe that the ring closures of
nonfluorinated diaryl-1,5-diazapentadienes derivatives
proceed by intramolecular electrophilic aromatic substi-
tution; however, an electrocyclic course of the ring closure
was also proposed.23,25 Other authors suggest that no
rigorous discrimination between the two mechanism may
be relevant, because 1,5-diazapentadienes analogues
exist as a tautomeric equilibrium and both types of
cyclization mechanisms could occurs.36
Experimental Section
General Procedure for the Preparation of 2-Triflu-
oromethyl-quinolines 5a-g. Method A. In a typical pro-
cedure, a mixture of the gem-iodoacetylated compound 3 (1
equiv) and arylamines 4 (3 equiv) in dichloromethane (5 mL/1
g of 3) was refluxed at 40 °C until disappearance of 19F NMR
signals corresponding to the starting product 3 (12-24 h). The
reaction mixture was concentrated under reduced pressure and
then stirred with diethyl ether. An excess of petroleum ether
was added; the precipitate that had formed was eliminated
by vacuum filtration and washed three times with petroleum
ether. The filtrate was concentrated in vacuo to give a brown
oil. Chromatography on silica gel column (eluent, petroleum
ether/ethyl acetate 98/2) left a yellow oil which was crystallized
from methanol/water to give pure samples of the corresponding
quinolines 5a-g.
2-Trifluoromethylquinoline 5a. Starting with 3 (5 g; 15
mmol) and aniline (4.2 g; 45.18 mmol) in 25 mL of dichlo-
romethane under reflux for 12 h, 2.74 g of title quinoline is
obtained, total yield 93%. Spectral data in acetone-d6: 1H NMR
δ 7.8 (m, 1H), 7.9 (m, 2H), 8.1 (d, J ) 7.5 Hz, 1H), 8.2 (d,
In acidic conditions (acetic acid) we found that diaza-
pentadiene compound 6a-j gives quinolines 5a-k in
(36) Jutz, J. C. Top. Curr. Chem. 1978, 73, 125-230.
8330 J. Org. Chem., Vol. 70, No. 21, 2005

Synthesis of 2-Trifluoromethyl-1,5 Diazapentadienes
J ) 8.6 Hz, 1H), 8.7 (d, J ) 8.6 Hz, 1H); 13C NMR δ 117.6 (q,
General Procedure for the Synthesis of 2-Trifluoro-
methyl-1,5-diazapentadiene 6h-j. Method D. A mixture
of gem-iodoacetate compound 3 (1 equiv) and arylamines 4 (2
equiv) in dichloromethane (10 mL/1 g of 3) was refluxed at 40
°C until disappearance of 19F NMR signals corresponding to
the starting product 3 (2-3 h). The reaction mixture was
concentrated in vacuo and then diluted with diethyl ether. An
excess of petroleum ether was added, and the precipitate that
had formed was eliminated by vacuum filtration and washed
three times with petroleum ether. The filtrate was concen-
trated under reduced pressure to give brown oil. Chromatog-
raphy on silica gel column (eluent, petroleum ether/ethyl
acetate 5/95) left a yellow solid that was recrystallized from
ether/hexane to give pure compounds.
3
1
CH, JCF ) 2.1 Hz), 122.6 (q, CF3, JCF ) 273.8 Hz), 127.4,
130, 130.2, 134.1, 138.5, 141, 146.8 (q, C-CF3, 2JCF ) 34.1 Hz);
19F NMR -67.9 (s, 3F). MS (m/z): 198 (M+, 100). HRMS calcd
for C10H7F3N 198.0452, found 198.0455. Anal. Calcd for
C10H6F3N: C, 60.92; H, 3.07; N, 7.10. Found: C, 60.62; H, 3.42;
N, 6.77.
General Procedure for the Preparation of 2-Trifluo-
romethylquinolines 5h-k. Method B. A mixture of com-
pound 2 (1 equiv) and arylamines 3 (3 equiv) in dichloroethane
(5 mL/1 g of 2) was refluxed at 80 °C; the evolution of the
reaction was controlled by 19F NMR spectroscopy. At the end
of the reaction (12-36 h) the mixture was filtered and purified
by chromatography as described in Method A.
3-Trifluoromethyl-1-(4-nitrophenylamino)-3-(4-nitro-
phenylimino)-propene 6h. Starting with 3 (8.5 g; 25.6 mmol)
and p-nitroaniline (7 g; 51.2 mmol), in 85 mL of dichlo-
romethane. The mixture was stirred for 2 h; 6 g of title
diazapentadiene is obtained, total yield 62%. Spectral data in
DMSO-d6: 1H NMR δ 5.4 (d, J ) 13.6 Hz, 1H), 6.8 (d, J ) 8.1
Hz, 2H), 7.1 (d, J ) 8.3 Hz, 2H), 7.3 (d, J ) 8.3 Hz, 2H), 7.4
2-Trifluoromethyl-6-nitroquinoline 5h. Starting with 3
(5 g; 15.06 mmol) and p-nitroaniline (6.23 g; 45.18 mmol), in
25 mL of dichloroethane at 80 °C for 24 h, 3.16 g of title
quinoline is obtained, total yield 87%. Spectral data in acetone-
d6: 1H NMR δ 8.2 (d, J ) 8.6 Hz, 1H), 8.4 (d, J ) 9.3 Hz, 1H),
8.6 (dd, J ) 2.5 and 9.3 Hz, 1H), 9.1 (d, J ) 8.6 Hz, 1H) 9.19
3
(d, J ) 2.5 Hz, 1H); 13C NMR δ 119.5 (q, CH, JCF ) 2.2 Hz),
122 (q, CF3, 1JCF ) 275.4 Hz), 127.5, 130.1, 132, 132.8, 134.5,
(d, J ) 8.1 Hz, 2H), 7.6 (t, J ) 12.9 Hz, 1H), 9.9 (d, J ) 12.1
1
Hz, 1H); 13C NMR δ 89.1, 114.4, 116.1, 118 (q, CF3, JCF
)
2
140.1, 145.2, 148 (q, C-CF3, JCF ) 34 Hz); 19F NMR -68.5
(s, 3F). MS (m/z): 243 (M+, 100). HRMS calcd for C10H6F3N2O2
243.0381, found 243.0408. Anal. Calcd for C10H5F3N2O2: C,
49.60; H, 2.08; N, 11.57. Found: C, 49.74; H, 2.12; N, 10.09.
General Procedure for the Synthesis of 2-Trifluoro-
methyl-1,5-diazapentadienes 6a-g. Method C. A mixture
of gem-iodoacetate compound 3 (1 equiv) and arylamines 4 (2
equiv) in dichloromethane (10 mL/1 g of 3) was stirred at room
temperature until disappearance of 19F NMR signals corre-
sponding to the starting product 3 (2-4 h). The reaction
mixture was concentrated in vacuo and then diluted with
diethyl ether. An excess of petroleum ether was added, and
the precipitated salts that had formed were eliminated by
vacuum filtration and washed three times with petroleum
ether. The filtrate was concentrated under reduced pressure
to give a brown oil. Chromatography on silica gel column
(eluent, petroleum ether/ethyl acetate 98/2) left a yellow solid
that was recrystallized from ether/hexane to give pure com-
pounds.
279.6 Hz) 118.9, 123.5, 125.6, 126.9, 127.1, 137.1, 138.5, 145.9,
151.6 (q, C-CF3, 2JCF ) 31.5 Hz); 19F NMR -65.6 (s, 3F). MS
(m/z): 381 (M+, 100). HRMS calcd for C16H11F3N4O4 380.0732,
found 380.0729. Anal. Calcd for C16H11F3N4O4: C, 50.53; H,
2.92; N, 14.73. Found: C, 50.55; H, 2.93; N, 14.71.
Reaction of Diazapentadienes 6 with Arylamines 4.
Diazapentadienes 6 (R3 ) H, p-Me, m-Me, o-Me, p-Cl, m-Cl,
p-NO2, m-COOH, p-CN) (15 mmol) were put in reaction with
1 molar equiv of the corresponding arylamines 4 in dichloro-
ethane. The mixture was refluxed at 80 °C for 6 h. The reaction
was monitored by 19F NMR spectroscopy. At the end of the
reaction, chromatography on a silica gel column (eluent,
petroleum ether/ethyl acetate, 98/2) left a yellow oil that was
crystallized from methanol/water. The corresponding quino-
lines are obtained with high yields (>90%) and were assigned
by 19F, 1H, and 13C NMR spectroscopy and analyzed by HRMS.
Reaction of Diazapentadienes 6 with Acetic Acid.
Diazapentadiene 6 (R3 ) H, p-Me, m-Me, o-Me, p-Cl, m-Cl,
p-NO2, m-COOH, p-CN) (15 mmol) was dissolved in a solution
of dichloroethane/acetic acid, 1/1, v/v. The mixture was heated
at 80 °C for 6 h. Classical workup procedure as described
previously afforded in very high yields quinolines 5 (>95%),
3-Trifluoromethyl-1-phenylamino-3-phenyliminopro-
pene 6a. Starting with 3 (8.2 g; 24.69 mmol) and aniline (4.59
g; 49.39 mmol), in 85 mL of dichloromethane. The mixture was
stirred for 2 h; 6 g of title diazapentadiene is obtained, total
yield 86%. Spectral data in DMSO-d6: 1H NMR δ 5.5 (d, J )
13.7 Hz, 1H), 6.8 (d, J ) 7.5 Hz, 2H), 7 (m, 3H), 7.15 (t, J )
7.4 Hz, 1H), 7.3 (t, J ) 7.8 Hz, 2H), 7.4 (t, J ) 7.7 Hz, 2H), 7.6
(t, J ) 13 Hz, 1H), 9.9 (d, J ) 12.3 Hz, 1H); 13C NMR δ 90.8,
115, 119.2, 120.6 (q, CF3, 1JCF ) 279.2 Hz), 122.14, 123.6, 129.3,
1
which were assigned and identified by 19F, H, and 13C NMR
spectroscopy and analyzed by HRMS.
Supporting Information Available: Experimental pro-
cedures for syntheses and analytical data of compounds 5b-
g, 5i-k, 6b-g, and 6i-j; copies of 1H NMR spectra of
compounds 5a-k and compounds 6a-j; copies of 19F and 13C
spectra of compounds 6a, 6d, and 6g. This material is available
free of charge via the Internet at http://pubs.acs.org.
3
129.6, 140.64, 140.8 (q, CH, JCF ) 3 Hz), 149.5, 153.3 (q,
2
C-CF3, JCF ) 30.5 Hz); 19F NMR -65.8 (s, 3F). MS (m/z):
291 (M+, 100). HRMS calcd for C16H14F3N2 291.1109, found
291.1087 Anal. Calcd for C16H14F3N2: C, 66.20; H, 4.51; N, 9.65.
Found: C, 66.15; H, 4.31; N, 9.45.
JO050586D
J. Org. Chem, Vol. 70, No. 21, 2005 8331