Synthesis and spectral data of quinoline products obtained by reaction of N-(4-pyridinyliden)anilines and N-benzylidenaniline with 2,2-dimethoxypropane (Kametani reaction)

Article abstract of DOI:10.1002/jhet.5570440308

(Chemical Equation Presented) A study on interaction between N-(4-pyridinyliden)anilines 1-4 and 2,2-dimethoxypropane under Kametani reaction conditions was realized. According to the GC-MS analysis of crude reaction, besides the needed 4-methyl-2-(4-pyri

Full text of DOI:10.1002/jhet.5570440308

May-Jun 2007
551
Synthesis and Spectral Data of Quinoline Products Obtained by
Reaction of N-(4-Pyridinyliden)anilines and N-Benzylidenaniline
with 2,2-Dimethoxypropane (Kametani Reaction)
Vladimir V. Kouznetsov,* Carlos M. Meléndez Gómez, Juan M. Urbina González,
Elena E. Stashenko
Laboratorio de Química Orgánica y Biomolecular, Escuela de Química, Universidad Industrial de Santander,
A.A. 678, Bucaramanga, Colombia.
Alí Bahsas and Juan Amaro-Luis
Laboratorio de RMN, Grupo de Productos Naturales, Departamento de Química, Universidad de los Andes,
Mérida 5101, Venezuela
Received March 23, 2006
R
R
N
NH
NH
NH
R
N
+
BF3.OEt2
O
N
.
N
BF3 OEt2
5-8
9-12
O
O
CH2Cl2, Δ, 14 h
22
23
+
CH2Cl2, 14 h, rt
R
R
N
X
O
X = N
R = H
X = N
1-4
N
N
NH
+
X = N, C-H
N
N
24
17-20
25
13-16
O
A study on interaction between N-(4-pyridinyliden)anilines 1-4 and 2,2-dimethoxypropane under
Kametani reaction conditions was realized. According to the GC-MS analysis of crude reaction, besides
the needed 4-methyl-2-(4-pyridinyl)quinolines 5-8, three collateral products: secondary amines 9-12, 4-(2-
methylprop-1-enyl)quinolines 13-16 and 4-(2-methoxy-2-methylpropyl)quinolines 17-20 were formed.
Unexpected quinolines 13-16 as well the desired quinolines 5-8 were isolated and fully characterized. In
contrast, a condensation of N-benzylidenaniline 21 with 2,2-dimethoxypropane afforded a set of different
quinoline products.
J. Heterocyclic Chem., 44, 551 (2007).
reactions. The latter consists on the interaction between N-
aryl aldimines and acetals (mainly, 2,2-dimethoxypropane
and 1,1-diethoxypropane) in the presence of Lewis acids.
Until now, Kametani reaction is little used in preparation of
quinoline derivatives, maybe, because its low efficiency.
However, this reaction could become a simple route to
various substituted 4-methylquinolines if appropriate acid
catalysts would be developed. The acetals are more stable
and available than the vinyl ethers or ketene acetals.
Keeping in view the above facts, we wanted to prepare new
C-2 4-pyridinyl substituted 8-alkyl-4-methylquinolines
needed in our investigations on the search for antifungal
quinolines [8,9]. Here we report our comparative study on
condensation of N-(4-pyridinyliden)anilines and N-benzyl-
idenaniline with 2,2-dimethoxypropane under Kametani
reaction conditions.
INTRODUCTION
The quinoline nucleus occurs in several natural
compounds [1] and in some pharmacologically active
substances [2]. For instance, the 8-(diethylaminohexyl-
amino)-6-methoxy-4-methylquinoline is highly effective
against the protozoan parasite Trypanosoma cruzy, which is
the agent of Chagas' disease [3]. Several antitumoral
antibiotics are based on the 2-(2-pyridinyl)quinoline-
quinone tricyclic molecule [4]. Many syntheses of
quinolines are known, but due to their importance, the
development of new synthetic approaches remains an active
research area [5]. An acid-mediated cycloaddition between
the C=C-N=C azadiene moieties of N-aryl aldimines and
nucleophilic olefins like vinyl ethers is one of the most
convenient methods for quinoline preparation, which is
usually catalyzed by Lewis acids. BF3•OEt2 has been mainly
used for this purpose since the pioneering work of Povarov
[6]. Both Povarov reaction and Kametani reaction [7] can be
considered as [4+2] imino Diels-Alder cycloaddition
RESULTS AND DISCUSSION
The selected N-aldimines 1-4 were prepared by
refluxing a mixture in dry ethanol of 4-pyridinecarboxy

552
V. V. Kouznetsov, C. M. Meléndez Gómez, J. M. Urbina González, E. E. Stashenko,
A. Bahsas and J. Amaro-Luis
Vol 44
aldehyde and aniline or substituted anilines such as o-
methylaniline, o-ethylaniline, and o-isopropylaniline.
These N-(4-pyridinyliden)-2-alkylanilines were treated
with 2,2-dimethoxypropane in the presence of BF3•OEt2
in boiling dichloromethane (their interaction at room
temperature was not observed). We anticipated that the
however, we were able to isolate and fully characterize
the desired quinolines 5-8 and unexpected quinolines 13-
16. The quinoline 15 was not obtained in pure form. The
reduced products 9-12 of initial aldimines, which were
formed with yield 20-30% (GC-MS), are known
compounds [10,11].
Scheme I
R
R
N
NH
+
R
N
N
5-8
9-12
BF3.OEt2
N
R
N
O
R
CH2Cl2, Δ, 14 h
+
N
O
N
1-4
+
N
N
17-20
13-16
O
presence of the pyridine nitrogen of aldehyde component
would complicate the course of the reaction. To obtain the
desired 4-methyl-2-(4- pyridinyl)quinolines 5-8, an excess
BF3•OEt2 was used in this reaction. Common workup
procedure allowed us to obtain the resulting crudes, as red
oils, which were first analyzed by GC-MS method and
then purified by means of column chromatography on
silica gel. According to the GC-MS analysis of crude
reaction, besides the needed quinolines 5-8, three different
The mass spectra of the compounds 5-8 and 13-16
contain respective molecular ion M+. peaks of high
abundance, which confirms their molecular formula
(Table 1).
The structures of the C-2 pyridinyl substituted
quinolines 5-8 and 13-14,16 were strongly confirmed by
1H-, 13C-NMR spectra and 2D NMR spectroscopy. The 1H
NMR spectra of quinolines 5-8 registered the
characteristic signals generated by the two aromatic
Table 1
GC-MS Analysis
Found. M+, m/z
R
H
Compounds
tR, min
Min. Form.
Yield, %
5
27.25
31.51
35.02
28.99
32.51
35.81
29.86
33.89
36.74
30.25
33.75
37.00
220
260
292
234
274
306
248
288
320
262
302
334
C15H12N2
C18H16N2
C19H20N2O
C16H14N2
C19H18N2
C20H22N2O
C17H16N2
C20H20N2
C21H24N2O
C18H18N2
C21H22N2
C22H26N2O
25
6.5
*
20
7.5
*
30
**
*
26
10.5
*
13
17
6
14
18
7
15
19
8
16
20
Me
Et
i-Pr
* - not isolated from the crude; ** - not obtained in pure form.
products: secondary amines 9-12, 4-(2-methylprop-1-
enyl)quinolines 13-16 and 4-(2-methoxy-2-methyl-
propyl)quinolines 17-20 were formed (Scheme I).
All attempts to isolate the quinolines 17-20 by
conventional column chromatography were unsuccessful,
rings,- quinoline and pyridine protons appeared as clean
signals with their respective common constants in the
region from 7.10 to 8.82 ppm. 2-Methylprop-1-enyl
fragment in the quinolines 13-14 and 16 was also
1
confirmed by the H NMR spectra, where two three-

May-Jun 2007
Synthesis and Spectral Data of Quinoline Products
553
proton doublets at 1.81-1.85 and 2.11-2.12 ppm and one-
proton multiplet at 6.68-6.71 ppm were observed. The
13C-NMR spectra and bi-dimensional techniques as
1H,1H-COSY and HMQC also indicated the presence of
this fragment, for the case of compound 16, COSY
spectra show the correlations corresponding to the
quinoline system are observed and confirm that this stays
intact, besides the existence of the interactions among the
methyl protons (2'-CH3 and 3'-CH3) and olefin proton (1'-
H) (δ, 2.06/6.65).
Based on previous works [7,12,13], the formation of
obtained compounds from interaction between N-(4-
pyridinyliden)anilines and 2,2-dimethoxypropane under
Kametani reaction conditions could be better explained by
the following possible mechanistic scheme (Scheme II).
In the presence of an excess BF3•OEt2 and under heating,
2,2-dimethoxypropane could generate molecules of 2-
methoxypropene and O-methyl acetone oxonium ion that
play a key role in the formation of identified compounds.
A molecule of 2-methoxypropene and Lewis acid-
complex of initial aldimine might provide fist 4-methoxy-
4-methyltetrahydroquinoline derivative I and then 4-
methyl-1,2-dihydroquinoline derivative II, which could
serve as an hydride source for initial aldimine to give the
quinolines 5-8 and amines 9-12 [14]. These formed
quinolines, having reactive methyl group at 4-position,
could react with a molecule of O-methyl acetone oxonium
ion affording small amounts of collateral quinolines, first
13-16 and then 17-20.
In contrast, a catalyzed interaction between N-
benzylidenaniline 21 and 2,2-dimethoxypropane did not
need heating of the reaction mixture and afforded a set of
different compounds. According to the GC-MS analysis
of crude reaction, besides the expected quinoline 25 and
N-benzylaniline 24, two different products 22,23 that
could be intermediates in Kametani reaction (Scheme III).
However, 4-methyl-1,2-dihydroquinoline derivative III
was not detected in this experiment, the major product
(62%) in this crude was the 4-methoxy-4- methyltetra-
hydroquinoline 23, which have been isolated as a red oil.
Their GC-MS analysis indicated at two diastereoisomers
with tR 10.91 and 12.53 min. Moreover, when this inter-
Scheme II
O
1-4
O
N
H
N
H
R
N
R
N
I
II
1-4
O
O
+
9-12
O
N
R
N
5-8
17-20
N
R
N
13-16
Scheme III
NH
NH
O
BF3.OEt2
24
N
NH
22
O
CH2Cl2, r.t.
+
O
III
N
NH
21
O
BF3.OEt2
CH2Cl2
25
23

554
V. V. Kouznetsov, C. M. Meléndez Gómez, J. M. Urbina González, E. E. Stashenko,
A. Bahsas and J. Amaro-Luis
Vol 44
cm-1, ν = 2950 cm-1. 1H nmr (deuterium chloroform): δ 8.82 (dd,
2H, J = 4.5, 1.5 Hz, Hα,α'-Py), 8.14 (dd, 2H, J = 4.5, 1.5 Hz, Hβ,β'-
Py), 8.24 (d, 1H, J = 8.6 Hz, 8-H), 8.08 (dd, 1H, J = 8.4, 0.8 Hz,
5-H), 7.81 (ddd, 1H, J = 8.4, 6.0, 1.5 Hz, 7-H), 7.80 (d, 1H, J =
1.0, 3-H), 7.66 (ddd, 1H, J = 8.4, 6.0, 1.3 Hz, 6-H), 2.85 (d, 3H,
J =1.0, 4-CH3); gc-ms: tR: 24.93 min., ms: m/z: 220 (molecular
ion). Anal. Calcd. for C15H12N2: C, 81.79; H, 5.49; N, 12.72.
Found: C, 81.66; H, 5.76; N, 12.50.
mediate was subjected in the same reaction conditions, the
4-methyl-2-phenylquinoline 25 was formed in 42%
yields. These results agree with other investigations about
Povarov reaction [6,15] and can help with investigations
on the mechanistic aspects of the imino Diels-Alder
reactions.
Although the yields of the desired 4-methyl-2-(4-
pyridinyl)quinolines 5-8 were low, it was possible to
screen them for antifungal and anticancer activities. These
quinolines were active against a panel of standardized
dermatophytes, and also active against breast (MCF-7),
lung (H-460) and central nervous system (SF-268) human
cancer cell lines that make them attractive models in the
search for potential bioactive agents [16]. The search of
appropriate acid catalyst in this reaction and its
mechanistic details are currently under study in our
laboratories.
The compound 13 was obtained in 6.5% yield, red oil. 1H nmr
(deuterium chloroform): δ 8.78 (d, 2H, J = 5.0 Hz, Hα,α'-Py), 8.18
(d, 1H, J = 8.0 Hz, 8-H), 8.05 (d, 2H, J = 5.0, 3.0 Hz, Hβ,β'-Py),
8.02 (d, 1H, J = 9.0 Hz, 5H), 7.74 (m, 1H, 7-H), 7.70 (s, 1H, 3-
H), 7.39 (m, 1H, 6-H), 6.68 (m, 1H, 1'-H), 2.11 (d, 3H, J = 1.2
Hz, 2'-CH3), 1.81 (d, 3H, J = 1.1 Hz, 3'-CH3), 13C nmr (100
MHz): δ 153.1 (2-C), 150.5 (Cα,α'-Py), 147.3 (5a-C), 145.2 (8a-
C), 141.4 (2'-C), 138.4 (Cβ''-Py), 130.4 (8-C), 129.5 (7-C), 127.6
(6-C), 126.2 (4-C), 124.7 (5-C), 122.1 (Cβ,β'-Py), 120.3 (1'-C),
118.7 (3-C), 26.4 (2'-CH3), 19.8 (3'-CH3); COSY correlations
[δH/δH (H/H)]: 8.78/8.02 (Hα,α'-Py /Hβ,β'-Py), 8.18/7.74(H8/H7),
8.05/7.39 (H5/H6), 8.02/8.78 (Hβ,β'-Py/Hα,α'-Py ), 7.74/8.18/7.39
(H7/H8/H6), 7.39/8.05/7.74 (H6/H5/H7), 6.68/2.11/1.81 (H1'/H2'-
Me3/H3'-Me3), 2.11/6.68 (H2'-Me3/H1'), 1.81/6.68 (H3'-Me3/H1');
HMQC correlations [δH/δC (C/H)]: 8.78/150.5 (Hα,α'-Py/Cα,α'-Py),
8.02/122.1 (Hβ,β'-Py/Cβ,β'-Py), 8.18/130.4 (H8/C8), 8.05/124.7
(H5/C5), 7.74/129.5 (H7/C7), 7.70/118.7 (H3/C3), 7.39/127.6
EXPERIMENTAL
Melting points were uncorrected and measured in a FISHER-
JOHNS melting point apparatus. Infrared spectra were recorded
on a Nicolet Avatar 360 FT-IR spectrometers as KBr pellets or
neat. The 1H and 13C nmr spectra were determined on either
Inova-400 or Bruker AM-400, in deuterochloroform with
tetramethylsilane as internal standard. Data are reported as
follows: chemical shifts (multiplicity, number of protons,
coupling constants and group). Mass spectra were recorded with
a HP 5890 A Series II, link to a network Mass selective detector
HP 5972, a mass spectrometer with 70 eV electron impact
ionization. The purities of the obtained substance were
monitored by thin layer chromatography on Silufol UV254
sheets. Elemental analyses were performed on a Leco CHN-600
analyzer. Solvents and common reagents obtained from Merck
and Aldrich were reagent grade.
General procedure for the reaction of 4-Pyridine-
carboxyaldehyde with Anilines. Equimolar solutions of the
anilines (1.00 mol) and 4-pyridinecarboxyaldehyde (1.00 mol) in
dry ethanol (15 ml) were heated at reflux during 1 h. The ethanol
was removed by distillation and the residual material
crystallized from petroleum ether. The substituted N-(4-
pyridinyliden)anilines 1-4 were isolated as red oils, which were
used in the Kamateni reaction without further purification.
General procedure for Reaction of Aldimines 1-4 with 2,2-
Dimethylpropane. A solution of the appropriate aldimine 1-4
(1.00 mmol) in anhydrous CH2Cl2 (15 mL) was cooled to 0 °C.
Over a period of 20 min, 0.39 g (2.8 mmol) of BF3•OEt2 was
added dropwise. The resulting mixture was allowed to warm to
room temperature and 2,2-dimethoxypropane (1.02 g, 9.8 mmol)
in CH2Cl2 (10 mL) was then rapidly added with vigorous
stirring. The reaction mixture was stirred at gentile reflux for 15
h and then quenched with H2O. The organic layer was separated,
and dried with Na2SO4. The organic solvent was removed in
vacuo. The residue was purified by chromatography column
(silica gel) to afford the respective 4-methylquinolines 5-8 and
4-(2-methylprop-1-enyl)quinolines 13-16.
,
(H6/C6), 6.68/120.3 (H1'/C1'), 2.11/26.4 (H2 -Me3/C2'-Me3),
1.81/19.8 (H3'-Me3/3'-C); gc-ms: tR: 31.51 min., m/z: 260
(molecular ion). Anal. Calcd. for C18H16N2: C, 83.04; H, 6.19;
N, 10.76. Found: C, 82.95; H, 6.34; N, 10.75.
4,8-Dimethyl-2-(4-piridinyl)quinoline (6) and 4-(2-
methylprop-1-enyl)-8-methyl-2-(4-pyridinyl)-quinoline (14).
The compound 6 was obtained in 20% yield, m.p. 72-74°C. ir:
1
3026, 2951, 1592 cm-1. H nmr (deuterium chloroform): δ 8.82
(dd, 2H, J = 4.8, 1.8 Hz, Hα,α'-py), 8.26 (dd, 2H, J = 4.5, 1.5 Hz,
Hβ,β'-py), 7.92 (d, 1H, J = 8.3 Hz, 5-H), 7.82 (s, 1H, 3-H), 7.66 (d,
1H, J = 7.1 Hz, 7-H), 7.53 (dd, 1H, J = 8.3, 7.1 Hz, 6-H), 2.94 (s,
3H, 8-CH3), 2.83 (d, 3H, J = 0.8 Hz , 4-CH3). gc-ms: tr: 25.94
min., m/z: 234 (molecular ion). Anal. Calcd. for: C16H14N2: C,
82.02; H, 6.02; N, 11.96. Found: C, 82.14; H, 6.23; N 11.67.
The compound 14 was obtained in 7.3% yield, red oil. 1H nmr
(deuterium chloroform) δ 8.81 (dd, 2H, J = 4.6, 1.7 Hz, Hα,α'-Py),
8.05 (dd, 2H, J = 4.6, 1.7 Hz, Hβ,β'-Py), 7.89 (d, 1H, J = 8.3 Hz, 5-
H), 7.76 (s, 1H, 3-H), 7.62 (d, 1H, J = 6.8 Hz, 7-H), 7.47 (dd,
1H, J = 8.3, 7.0 Hz, 6-H), 6.70 (m, 1H, 1'-H), 2.95 (s, 3H, 8-
CH3), 2.11 (d, 3H, J = 1.5 Hz, 2'-CH3), 1.83 (d, 3H, J = 1.1 Hz,
3'-CH3); 13C nmr (100 MHz): δ 152.8 (2-C), 150.4 (Cα ,α'-Py),
148.9 (8a-C), 145.5 (4-C), 131.7 (Cβ''-Py), 129.3 (7-C), 128.8 (2'-
C), 128.6 (8-C), 122.4 (5a-C), 122.2 (5-C), 120.8 (Cβ,β'-Py), 120.9
(1'-C ), 118.0 (3-C), 26.6 (2'-CH3), 18.2 (8-CH3); COSY
correlations [δH/δH (H/H)]: 8.75/8.11 (Hα,α'-Py/Hβ,β'-Py), 8.11/8.75
(Hβ,β'-Py/Hα,α'-Py), 7.83/7.42 (H5/H6), 7.56/7.42 (H7/H6),
7.42/7.82/7.56 (H6/H5/H7), 6.65/2.06/1.79 (H1'/H2'-Me3/H3'-Me3),
2.06/6.65 (H2'-Me3/H1'), 1.78/6.66 (H3'-Me3/H1'); HMQC
correlations [δH/δC (C/H)]: 8.75/150.4 (Hα,α'-Py/Cα,α'-Py),
8.11/120.8 (Hα,α'-Py/ Cβ,β'-Py), 7.83/ 122.2 (H5/C5), 7.70/118.0
(H3/C3), 7.56/129.3 (H7/C7), 7.41/126.4 (H6/C6), 6.65/120.8
(H1'/C1'), 2.89/18.5 (H8-Me3/C8-Me3), 2.06/26.6 (H2'-Me3/C2'-Me3),
1.78/19.6 (H3'-Me3/3'-C); gc-ms: tR: 32.51 min., m/z: 274
(molecular ion). Anal. Calcd. for C19H18N2 :C, 83.18; H, 6.61;
N, 10.21. Found: C, 83.23; H, 6.75; N, 10.03.
4-Methyl-2-(4-piridinyl)quinoline (5) and 4-(2-methyl-
prop-1-enyl)-2-(4-pyridinyl)quinoline (13). Compound 5 was
obtained in 25% yield, red oil. ir (potassium bromide): ν =3034
8-Ethyl-4-methyl-2-(4-piridinyl)quinoline (7) and 4-(2-
methylprop-1-enyl)-8-ethyl-2-(4-piridinyl)quinoline (15). The

May-Jun 2007
Synthesis and Spectral Data of Quinoline Products
555
1
compound 7 was obtained in 30% yield, m.p. 72-74°C. H nmr
(deuterium chloroform) δ 8.82 (dd, 2H, J = 4.8, 1.8 Hz, Hα,α'-Py),
8.25 (dd, 2H, J = 4.8, 1.7 Hz, Hβ,β'-Py), 7.92 (dd, 1H, J = 8.3, 1.5
Hz, 5-H), 7.83 (d, 1H, J = 0.8 Hz, 3-H), 7.66 (d, 1H, J = 7.1 Hz,
7-H), 7.57 (dd, 1H, J = 8.3, 7.1 Hz, 6-H), 3.46 (c, 2H, J = 7.6,
7.3 Hz, 8-CH2-CH3), 2.83 (d, 3H, J = 0.8 Hz, 4-CH3), 1.48 (t,
3H, J = 7.6 Hz, 8-CH2-CH3). gc-ms tR: 34.97 min., m/z: 248
(molecular ion). Anal. Calcd. for C17H16N2: C, 82.22; H, 6.49;
N, 11.28. Found: C, 82.12; H, 6.79; N, 11.07. The compound 15
was not separated in pure form.
1 (heptane) – yellow liquid, 0.15 g (15%) - contains N-benzyl-
aniline 24 (tR = 22.02 min, m/z 183 - molecular ion) and
quinoline 25 (tR = 31.12 min, m/z 219 - molecular ion). Fraction
2 (heptane-ether, 1:10) – red oil, 4.20 g, (70%) - contains 4-
methoxy-4-methyltetrahydroquinoline 23 (two diastereomers, tR
10.91 and 12.53 min, m/z 145 (M-CH3OH)) and aminoketone 22
(tR 27.86 min, m/z 239 - molecular ion) that was not obtained in
pure form.
4-Methyl-2-phenylquinoline (25) was obtained in 7.0% yield;
spectral data are agreed with published data [14]. 4-Methoxy-4-
methyl-1,2,3,4-tetrahydroquinoline (23) was obtained in 62%
yield; spectral data are agreed with published data [14].
Procedure for Conversion of 4-Methoxy-4-methyl-1,2,3,4-
tetrahydroquinoline 23 into the corresponding quinoline 25.
A mixture of tetrahydroquinoline 23 (2.63 g, 0.011 mol) and
8-Isopropyl-4-methyl-2-(4-piridinyl)quinoline (8) and 4-(2-
methylprop-1-enyl)-8-isopropyl-2-(4-piridinyl)quinoline (16).
The compound 8 was obtained in 26% yield red oil. ir: 2960,
2926, 1596 cm-1. H RMN (deuterium chloroform) δ 8.77 (dd,
1
2H, J = 5.0, 2.0, Hz, Hα,α'-Py), 8.13 (dd, 2H, J = 4.0, 1.0 Hz, Hβ,β'-
Py), 7.88 (dd, 1H, J = 8.0, 1.0 Hz, 5-H ), 7.77 (s, 1H, 3-H), 7.64
(dd, 1H, J = 7.0, 1.0 Hz, 7-H), 7.55 (dd, 1H, J = 7.0, 1.0 Hz, 6-
H), 4.50 (sept, 1H, J = 7.0 Hz, 8-CH(CH3)2), 2.78 (d, 3H, J = 0.8
Hz, 4-CH3), 1.44 (d, 6 H, J = 7.0 Hz, 8-CH(CH3)2); gc-ms: tR:
27.48 min., m/z: 262 (molecular ion). Anal. Calcd. for C18H18N2:
C, 82.41; H, 6.92; N, 10.68. Found: C, 82.45; H, 6.57; N, 10.89.
.
BF3 OEt2 (2.42 g, 0.021mol) was stirred at gentile reflux for 2 h
and then pored into H2O and NaHCO3 (pH ~ 10). After common
work-up, the quinoline 25 was obtained in 42 % yield. Its
spectral data was identical with previously reported data [14].
Acknowledgments. This work was supported by the grant of
Instituto Colombiano para el Desarrollo de la Ciencia y la
Tecnología “Francisco José de Caldas” (COLCIENCIAS,
Proyecto: CENIVAM).
1
The compound 16 was obtained in 10.5% yield, red oil. H
nmr (deuterium chloroform) δ 8.81 (dd, 2H, J = 4.4, 1.5 Hz,
Hα,α'-Py), 8.18 (dd, 2H, J = 4.6, 1.7 Hz, Hβ,β'-Py), 7.89 (dd, 1H, J =
8.3, 1.3 Hz, 5-H), 7.77 (s, 1H, 3-H), 7.68 (dd, 1H, J = 7.0, 1.1
Hz, 7-H), 7.56 (dd, 1H, J = 8.1, 7.2 Hz, 6-H), 6.71 (m, 1H, 1'-H),
4.56 (Sep, 1H, J = 7.0 Hz, 8-CH), 2.12 (d, 3H, J = 1.3 Hz, 2'-
CH3), 1.85 (d, 3H, J = 1.3 Hz, 3'-CH3), 1.50 (d, 6H, J = 7.0 Hz,
8-CH3); 13C nmr (100 MHz): δ 151.7 (2-C), 150.6 (Cα,α'-Py),
147.3 (8a-C), 145.6 (4-C), 133.2 (8-C), 131.8 (Cβ''-Py), 126.9 (6-
C), 125.6 (7-C), 122.6 (5-C), 121.6 (Cβ,β'-Py), 121.1 (1'-C), 119.4
(5a-C), 118.0 (3-C), 28.0 (8-CH), 26.5 (2-CH3), 23.7 (8-CH3),
20.0 (3'-CH3); COSY correlations [δH/δH (H/H)]: 8.75/8.12
(Hα,α'-Py/Hβ,β'-Py), 8.12/8.75 (Hβ,β-Py/Hα,α'-Py), 7.84/7.50(H5/H6),
7.62/7.50 (H7/H6), 7.50/7.84/7.63 (H6/H5/H7), 6.64/2.05/1.79
(H1'/H2'-Me3/H3'-Me3), 4.50/1.46 (H8-CH/H8-Me3), 2.06/6.65 (H2'-
Me3/H1'), 1.79/6.65 (H3'-Me3/H1'), 1.45/4.50 (H8-Me3/H8-CH); HMQC
correlations [δH/δC (C/H)]: 8.75/150.6 (Hα,α'-Py/Cα,α'-Py),
8.12/121.5 (Hβ,β'-Py/Cβ,β'-Py), 7.84/ 122.6 (H5/C5), 7.72/118.0
(H3/C3), 7.62/125.6 (H7/C7), 7.50/126.9 (H6/C6), 6.66/121.6
(H1'/C1'), 4.50/28.0 (H8-CH/C8-CH), 2.06/26.5 (H2'-Me3/C2'-Me3),
1.79/20.0 (H3'-Me3/3'-C), 1.45/23.4 (H8-Me3/C8-Me3); gc-ms: tR:
32.51 min., m/z: 274 (molecular ion). Anal. Calcd. for C21H22N2:
C, 83.40; H, 7.33; N, 9.26. Found: C, 83.23; H, 7.57; N, 9.19.
Procedure for Reaction of Aldimine 21 with 2,2-
Dimethylpropane. A solution of the aldimine 21 (5.0 g, 0.028
mol) in anhydrous CH2Cl2 (45 mL) was cooled to 0 °C. Over a
period of 20 min, 3.92 g (0.034 mol) of BF3•OEt2 was added
dropwise. The resulting mixture was allowed to warm to room
temperature and 2,2-dimethoxypropane (2.87 g, 0.028 mol) in
CH2Cl2 (20 mL) was then rapidly added with vigorous stirring.
The reaction mixture was stirred at room temperature for 48 h
and then quenched with saturated aquous NaHCO3 (pH ~ 10).
The organic layer was separated, and dried with Na2SO4. The
organic solvent was removed in vacuo. The residue (6.98 g,
98%) was fractionated by conventional column chromatography
(alumina, heptane and heptane-ether mixture) to afford two
major fractions that were analyzed by GC-MS method. Fraction
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[16] These biological results will be published elsewhere.