A highly efficient regioselective one-pot synthesis of 2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted tetrahydroquinolin-5-ones using K5CoW12O40·3H2O as a heterogeneous recyclable catalyst

Article abstract of DOI:10.1016/j.tet.2007.10.014

A systematic investigation into the regioselective one-pot, three-component condensation of enaminones 1a-g, β-dicarbonyl compounds 2a-c, and ammonium acetate in the presence of a catalytic amount of K₅CoW₁₂O₄₀·3H₂O (0.01 equiv or 1.0 mol %) under solvent free conditions, as well as in refluxing isopropanol, has been reported. The reaction was highly efficient to produce 2,3,6-trisubstituted pyridines 3a-g, 4a-g, and novel 2,7,7-trisubstituted-5,6,7,8-tetrahydroquinoline-5-ones 5a-g in excellent yields. The present procedure offers advantages of short reaction time, simple work-up, and the catalyst exhibited remarkable reusable activity.

Full text of DOI:10.1016/j.tet.2007.10.014

Available online at www.sciencedirect.com
Tetrahedron 63 (2007) 13024–13031
A highly efficient regioselective one-pot synthesis of
2,3,6-trisubstituted pyridines and 2,7,7-trisubstituted
tetrahydroquinolin-5-ones using K5CoW12O40$3H2O
as a heterogeneous recyclable catalyst
*
Srinivas Kantevari, Mahankhali Venu Chary and Srinivasu V. N. Vuppalapati
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 007, India
Received 15 April 2007; revised 16 September 2007; accepted 4 October 2007
Available online 6 October 2007
Abstract—A systematic investigation into the regioselective one-pot, three-component condensation of enaminones 1a–g, b-dicarbonyl com-
pounds 2a–c, and ammonium acetate in the presence of a catalytic amount of K5CoW12O40$3H2O (0.01 equiv or 1.0 mol %) under solvent
free conditions, as well as in refluxing isopropanol, has been reported. The reaction was highly efficient to produce 2,3,6-trisubstituted pyri-
dines 3a–g, 4a–g, and novel 2,7,7-trisubstituted-5,6,7,8-tetrahydroquinoline-5-ones 5a–g in excellent yields. The present procedure offers
advantages of short reaction time, simple work-up, and the catalyst exhibited remarkable reusable activity.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
tolerance. In view of these facts, development of an alter-
native one-pot procedure is crucial.12
Synthesis of the pyridine ring system and its derivatives1a–e
occupy an important place in the realm of natural and syn-
thetic organic chemistry, due to their therapeutic and phar-
macological properties. They have emerged as integral
backbones of over 7000 existing drugs.1a,2a–f The pyridine
ring is also an integral part of agrochemicals,3a,b preparative
organic chemistry,4 and in coordination chemistry.5 In addi-
tion to these important biological applications, pyridine
derivatives are ideal scaffolds for making libraries of drug-
like compounds, and to generate libraries of inhibitors of
HIV-1 protease6a–c and factor Xa. Thus, the synthesis of
these heterocycles is of current importance. Previously,
2,3,6-trisubstituted pyridine derivatives were synthesized
by the reaction of a 3-aminocrotonate with acetophenone
Mannich base hydrochlorides in refluxing ethanol.7,8 Further
Bagley et al. explored the Bohlmann–Rahtz reaction by re-
acting 3-aminocrotonate with acetylenic ketones.9 Recently,
synthesis of these pyridines is reported by the reaction of en-
aminones with b-dicarbonyl compounds in the presence of
ammonium acetate in refluxing acetic acid,10 or by using
Montmorillonite K10 in isopropanol.11 However, these
methods suffer from low yields, use of expensive or not read-
ily available starting materials, and exhibit limited substrate
The catalytic function of heteropoly compounds13 (hetero-
poly acids and salts) has attracted much attention and they
are used in solution as well as in the solid state. Due to their
weak super-acidic and redox properties, low toxicity, ease
of handling, low cost, stability, water tolerance, recover-
ability, and reusability, heteropoly compounds are useful
as versatile catalysts in reactions requiring electrophilic
catalysis.14 The successful applications of potassium
dodecatangestocobaltate trihydrate (K5CoW12O40$3H2O)14b
as electron transfer catalyst for a wide variety of organic
transformations15 prompted us16 to explore the potential of
K5CoW12O40$3H2O as catalyst for one-pot three-component
heterocyclocondensation process. In this paper, we describe
a general and practical route for the synthesis of 2,3,6-trisub-
stituted pyridines and 2,7,7-trisubstituted-5,6,7,8-tetrahydro-
quinoline-5-ones by the cyclocondensation of enaminones,
b-dicarbonyl compounds, and ammonium acetate, using
K5CoW12O40$3H2O (1 mol %) as the catalyst.
2. Results and discussion
Enaminones,17 being versatile substrates in the synthesis of
heterocyclic compounds and drug intermediates, were
chosen as starting material for the synthesis of 2,3,6-trisub-
stituted pyridines. They are generally prepared by the con-
densation of methyl aryl ketones with dimethylformamide
Keywords: Regioselectivity; Multi-component reactions; Enaminones;
Heterogeneous catalyst.
* Corresponding author. E-mail: kantevari@yahoo.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.014

S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
13025
dimethylacetal in refluxing xylene18 (Scheme 1, Table 1).
Although the method is readily adopted, there is no general
synthetic protocol for the preparation of enaminones. We
present here a systematic procedure for the preparation of
various enamino ketones 1a–g. All the compounds were
fully characterized by 1H and 13C NMR, IR and mass spec-
tral data.
In a typical experimental procedure, a mixture of ethyl aceto-
acetate 2a or acetyl acetone 2b, enaminone 1a–g, and ammo-
nium acetate was reacted in isopropanol (IPA) solvent
(Method A, Table 3) and under solvent free conditions
(Method B, Table 3), in the presence of a catalytic amount
of K5CoW12O40$3H2O (1 mol %). Decreased reaction times
in solvent free conditions (Method B) compared to the reac-
tion in IPA (Method A) is realized because of the increased
reactivity of the reactant in the solid state, and the fact that
water evaporates at the reaction temperatures. In order to
improve the yields, we performed the reaction using differ-
ent quantities of reagents. The best results were obtained
with 0.01:1:1:2 ratios of K5CoW12O40$3H2O, enaminoke-
tone, 1,3-dicarbonyl compound, and ammonium acetate,
respectively (Scheme 3). To examine the reaction under tra-
ditional conditions, a solution of b-dicarbonyl compound
2a,b, enaminone 1a–g, ammonium acetate, and isopropanol
was refluxed in the presence of a catalytic amount of
K5CoW12O40$3H2O (1 mol %) for a period of time (speci-
fied in Table 3) required to complete the reaction (TLC),
resulting in the formation of trisubstituted pyridines. After
completion of reaction the catalyst was recovered by sim-
ple filtration, and the trisubstituted pyridines 3a–g, 4a–g
isolated from the filtrate by recrystallization in methanol.
Under solvent free conditions, after completion of the reac-
tion, as indicated by TLC, the reaction mixture was
quenched with methanol, the catalyst was filtered out,
and the methanol solution was cooled to afford 2,3,6-trisub-
stituted pyridines as pure products. Moreover the catalyst
could be quantitatively recovered from the reaction mixture
by using simple filtration of the contents and washing with
solvent, and could be reused after thermal activation
(80 ꢀC). For example, the catalyst was reused in case of
4-nitrophenyl enaminoketone (entry 5, Table 3) more than
five times with no loss of activity. To study the generality
of the process, several examples illustrating the novelty
for the synthesis of 2,3,6-trisubstituted pyridines studied,
are summarized in Table 3.
O
H3C
H3C
O
O
O
CH3
Xylene
+
CH3
N
R
N
R
CH3
125 °C, 7h
CH3
CH3
1a-g
Scheme 1.
Table 1. Synthesis of enamino ketones 1a–g
S. No.
R
Product
Yielda (%)
Mp (ꢀC)
Ref.
1
2
3
4
5
6
7
C6H5
1a
1b
1c
1d
1e
1f
90
86
91
95
89
83
89
86–88
89–91
79–81
74–76
151–153
98–100
Oil
18a
10
10
—
—
10
—
p-CH3C6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-CH3OC6H4
1-Naphthyl
1g
a
Isolated yields.
Initially, the reaction of 3-dimethylamino-1-(4-chloro-
phenyl)-prop-2-en-1-one 1c, ethyl acetoacetate, and
NH4OAc was attempted under different sets of conditions
(Table 2). Of all the above combinations, the reaction in
IPA at reflux temperature (entry 3, Table 2) and under sol-
vent free conditions (entry 8, Table 2) using 1 mol % of
K5CoW12O40$3H2O as the catalyst, is found to be a novel,
one-pot combination that not only preserved the conditions
of one-pot reaction, but also consistently produced excellent
yields of the 2,3,6-trisubstituted pyridines (Scheme 2).
Table 2. Effect of reaction parameters on the synthesis of 2,3,6-trisub-
stituted pyridine 3c
Many of the pharmacologically relevant substitution pat-
terns on the aromatic ring of trisubstituted pyridines could
be introduced efficiently with a variety of enaminones in
high yields and high purity. However, the nature of the func-
tional group on the aromatic ring of the enaminones exerted
a strong influence on the reaction time.
S. No. Solvent
Catalyst
Temp Time Yielda
(ꢀC)
(min) (%)
1
2
Acetic acid Acetic acid10
118
60 8410
240 7911
120 85
240 64
240 52
iso-Propanol Montmorillonite K1011 82
3
4
5
iso-Propanol K5CoW12O40$3H2O
K5CoW12O40$3H2O
K5CoW12O40$3H2O
82
80
64
25
Ethanol
Methanol
6
7
8
9
10
11
12
13
iso-Propanol K5CoW12O40$3H2O
Solvent-free K5CoW12O40$3H2O
Solvent-free K5CoW12O40$3H2O
Solvent-free Silica-gel
240
0
An increase of the reaction rate was observed with enami-
nones bearing electron-withdrawing groups in the p-position
(entry 5, Table 3), in comparison to the unsubstituted enami-
nones. The presence of an electron donating (methoxy)
group (entry 6, Table 3) decreased both the rate of reaction
and the product yield. Acid sensitive b-dicarbonyl com-
pounds such as acetyl acetone and ethyl acetoacetate worked
well without the formation of any side products with variety
of structurally and electronically divergent substituents of
82
120 35
30 95
115
115
115
115
115
82
120 41
120 45
120 43
Solvent-free IR-120, H+
Solvent-free Dowex-50, H+
Solvent-free No catalyst
iso-Propanol No catalyst
120
5b
1400 13b
a
Isolated yields.
Yield based on 1H NMR.
b
O
O
O
OC2H5
CH3
OC2H5
N
N
3c
CH3
NH4OAc
+
+
CH3
O
CH3
2a
Cl
1c
Cl
Scheme 2.

13026
S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
Table 3. Synthesis of 2,3,6-trisubstituted pyridines 3a–g and 4a–g using K5CoW12O40$3H2O catalyst
Entry
R
R0
Product
Method A
Method B
Mp (ꢀC)
Ref.
Time (min)
Yielda (%)
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
C6H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
OC2H5
CH3
CH3
CH3
CH3
CH3
3a
3b
3c
3d
3e
3f
3g
4a
4b
4c
4d
4e
4f
120
150
120
120
120
150
150
120
180
120
120
120
180
180
86
84
30
45
30
35
30
45
45
50
60
45
45
30
60
60
95
93
43–45
53–55
74–75
73–75
142
48–50
Oil
110
82–84
58–60
76–78
131
100
Oil
11
11
11
11
11
11
—
11
—
—
—
—
—
—
p-CH3C6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-CH3OC6H4
1-Naphthyl
C6H5
p-CH3C6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-CH3OC6H4
1-Naphthyl
85
86
95
97
91b
98b
83
85
83
81
92
94
93
90
9
10
11
12
13
14
88
89
95
96
90, 89, 86b
97, 95, 92b
CH3
CH3
80
86
86
93
4g
a
Isolated yield.
The yields obtained after first, third, and fifth successive reuse of the catalyst.
b
Method A:
K5CoW12O40.3H2O
IPA, Reflux, 2-3h
(or)
O
O
O
CH3
R'
R'
R
N
+
NH4OAc
+
CH3
1a-g
Method B:
R
N
CH3
O
CH3
2a-b
K5CoW12O40.3H2O
3a-g; 4a-g
Neat, 115 °C, 0.5-1.0h
Scheme 3.
enaminones. Thus in the present protocol, variations in all
components have been accommodated very comfortably.
a variety of functional groups, such as NO2, Cl, Br, OCH3,
and various dicarbonyl compounds, and the catalyst is reus-
able under the reaction conditions.
In continuation of our synthetic experiments, we are de-
lighted with a new series of 2,7,7-trisubstituted-5,6,7,8-
tetrahydroquinoline-5-ones 5a–g (Scheme 4) in excellent
yields by the reaction of enaminones (1a–g), dimedone 2c,
and ammonium acetate in the presence of a catalytic amount
of K5CoW12O40$3H2O (1 mol %), under solvent free condi-
tions (Method B, Table 4) as well as in refluxing isopropanol
(Method A, Table 4). After completion of the reaction, the
catalyst is recovered by simple filtration, and the tetrahydro-
quinoline-5-ones 5a–g are isolated from the filtrate by re-
crystallization in methanol. The results are summarized in
Table 4. All the products 5a–g were fully characterized by
1H and 13C NMR spectroscopy, IR and mass spectral data
(see Supplementary data). The use of just 1 mol % of
K5CoW12O40$3H2O is sufficient to push the reaction for-
ward. Higher amounts of K5CoW12O40$3H2O did not im-
prove the result to a great extent. No additive or protic/
Lewis acid is necessary in the procedure. The products ob-
tained are of high purity (>95% by 1H NMR spectroscopy).
Another important aspect of this procedure is the survival of
In conclusion, a series of 2,3,6-trisubstituted pyridines 3a–g,
4a–g, and tetrahydroquinoline-5-ones 5a–g were synthe-
sized efficiently by regioselective one-pot condensation of
an enaminone 1, b-dicarbonyl compound 2a,b or dimedone
2c, respectively, and ammonium acetate in the presence of
a catalytic amount of K5CoW12O40$3H2O (0.01 equiv or
1.0 mol %) in isopropanol and under solvent free conditions.
The current protocol was applied successfully for the first
time to the synthesis of tetrahydroquinoline-5-ones 5a–g
from enaminones 1. The method has the ability to tolerate
structurally and electronically divergent substituents, either
in the enaminones or in the dicarbonyl compounds; variable
reaction conditions, shorter reaction times, and simple work-
up procedure are other advantages. Moreover, the catalyst
exhibited remarkable reusable activity. Further, the present
procedure is readily amenable to parallel synthesis and the
generation of combinatorial 2,3,6-trisubstituted pyridine
and 2,7,7-trisubstituted-5, 6,7,8-tetrahydroquinoline-5-one
libraries.
Method A:
K5CoW12O40.3H2O
IPA, Reflux, 2-3h
O
O
O
(or)
Method B:
CH3
CH3
CH3
+
NH4OAc
+
R
N
CH3
CH3
R
N
CH3
O
K5CoW12O40.3H2O
Neat, 115 °C, 0.5-1.0h
5a-g
1a-g
2c
Scheme 4.

S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
13027
Table 4. Reaction of enaminoketone and dimedone in the presence of
K5CoW12O40$3H2O catalyst
product was triturated with petroleum ether. The resulting
solid was filtered and washed with cold petroleum ether to
afford the pure product 1e as a yellowish brown solid
(3.916 g, 89%).
Entry
R
Product
Method A
Method B
Mp
(ꢀC)
Time Yielda Time Yielda
(min) (%) (min) (%)
3.3.1. 3-Dimethylamino-1-(phenyl)prop-2-enone 1a.
Yield 90%, mp 86–88 ꢀC (pet-ether, lit.16a 86–88 ꢀC); IR
(KBr) vmax 3423, 3020, 2909, 2805, 1639, 1584, 1543,
1427, 1362, 1309, 1275, 1234, 1110, 1049, 1019, 852, 739,
1
2
3
4
5
6
7
C6H5
5a
5b
5c
5d
5e
150
180
150
150
120
180
180
90
88
92
92
93b
87
91
45
60
50
45
45
60
60
94
91
97
96
98b
90
95
67
120
105
132
182
125
Oil
p-CH3C6H4
p-ClC6H4
p-BrC6H4
p-NO2C6H4
p-CH3OC6H4 5f
1-Naphthyl 5g
1
6967; H NMR (300 MHz, CDCl3, TMS) d 2.75–3.22 (6H,
2br s), 5.65 (1H, d, J¼14.7 Hz), 7.40 (3H, m), 7.70 (1H, d,
J¼15.2 Hz), 7.85 (2H, m); MS (EI) m/z 175 (M+, 34%),
158 (84), 98 (100), 91 (14), 77 (34), 55 (55), 51 (55). Anal.
Calcd for C11H13NO: C, 75.40; H, 7.48; N, 7.99. Found: C,
75.31; H, 7.55; N, 8.01.
a
Isolated yield.
The catalyst was reused at least for five times.
b
3. Experimental section
3.3.2. 3-Dimethylamino-1-(4-methylphenyl)prop-2-
enone 1b. Yield 86%, mp 89–91 ꢀC (pet-ether, lit.10 90–
91 ꢀC); IR (KBr) vmax 3428, 2915, 2802, 1644, 1579,
1538, 1433, 1355, 1280, 1237, 1113, 1055, 975, 900, 780;
1H NMR (300 MHz, CDCl3, TMS) d 2.40 (3H, s), 3.01
(6H, br 2 s), 5.68 (1H, d, J¼12.8 Hz), 7.18 (2H, d,
J¼7.5 Hz), 7.75 (3H, m); MS (EI) m/z 189 (M+, 33%),
172(87), 120 (26), 99 (100), 92 (26), 70 (43), 55 (52), 51
(31). Anal. Calcd for C12H15NO: C, 76.16; H, 7.99; N,
7.40. Found: C, 76.09; H, 7.91; N, 7.51.
3.1. General
All reagents and solvents were analytically pure, and were
used without further purification. Anhydrous conditions
were not required for this reaction. Melting points were mea-
sured with a Fischer–Johns melting point apparatus and are
1
uncorrected. H NMR spectra were taken in commercial
deuterated solvents on a multinuclear spectrometer with all
chemical shifts being reported in parts per million (d) rela-
tive to internal tetramethylsilane (TMS, d 0.0) or with the
solvent reference relative to TMS employed as the internal
standard CDCl3 (d 7.23 ppm). Data are reported as follows:
chemical shifts (multiplicity [singlet (s), doublet (d), triplet
(t), quartet (q), broad (br), and multiplet (m)], coupling con-
stants [Hz], integration). 13C NMR spectra were taken on
a multinuclear spectrometer (50 MHz), and the chemical
shifts are reported in parts per million (d unit) downfield
from tetramethylsilane as the internal standard (CDCl3,
d 77.0). Infrared spectra were recorded as thin films on
KBr plates with nmax in inverse centimeters. Mass spectra
were recorded under electron impact at 70 eV on Finnigan
Mat 1020B mass spectrometer. Elemental analyses were
performed on elemental analyzer Vario EL. Column chro-
matography was carried out using 60–120 mesh silica gel.
Thin layer chromatography was performed on Merck 60
F-254 pre coated silica gel plates.
3.3.3. 3-Dimethylamino-1-(4-chlorophenyl)prop-2-enone
1c. Yield 91%, mp 79–81 ꢀC (pet-ether, lit.10 80–81 ꢀC);
IR (KBr) vmax 3440, 2918, 2803, 1645, 1581, 1543, 1435,
1353, 1278, 1053, 899, 837, 787; 1H NMR (300 MHz,
CDCl3, TMS) d 2.82–3.32 (6H, br 2 s), 5.63 (1H, d,
J¼12.5 Hz), 7.35 (2H, d, J¼8.5 Hz), 7.68–7.86 (3H, m);
MS (EI) m/z 209 (M+, 42%), 192 (81), 139 (26), 125 (11),
111 (15), 98 (100), 70 (21), 55 (12), 42 (20). Anal. Calcd
for C11H12ClNO: C, 63.01; H, 5.77; N, 6.68. Found: C,
63.10; H, 5.66; N, 6.79.
3.3.4. 3-Dimethylamino-1-(4-bromophenyl)prop-2-enone
1d. Yield 95%, mp 74–76 ꢀC; IR (KBr) vmax 3446, 2912,
2805, 1640, 1578, 1540, 1438, 1356, 892, 805, 757; H
1
NMR (300 MHz, CDCl3, TMS) d 2.82–3.25 (6H, br 2 s),
5.60 (1H, d, J¼12.2 Hz), 7.52 (2H, d, J¼8.6 Hz), 7.70–
7.80 (3H, m); 13C NMR (50 MHz, CDCl3) d 36.9, 44.6,
91.2, 125.0, 128.8, 130.9, 138.9, 154.1, 186.6; MS (EI)
m/z 253 (M+, 32%), 238 (100), 183 (26), 157 (62), 55 (45).
Anal. Calcd for C11H12BrNO: C, 51.99; H, 4.76; N, 5.51.
Found: C, 51.87; H, 4.69; N, 5.59.
3.2. Preparation of potassium dodecatangestocobaltate
trihydrate (K5CoW12O40$3H2O) catalyst14
Cobaltous acetate (5.0 g, 0.02 mol), sodium tangestate
(39.6 g, 0.12 mol) was dissolved in acetic acid (5 mL) and
H2O at pH 6.5–7.5. This mixture was treated with KCl
(26.0 g) followed by potassium persulfate (21.0 g) in
H2SO4 (2 M, 80 mL); the precipitate was filtered, dried at
200 ꢀC, and crystallized in MeOH gave potassium dodeca-
tangestocobaltate trihydrate (K5CoW12O40$3H2O) as a light
blue solid (32.3 g, 51%).
3.3.5. 3-Dimethylamino-1-(4-nitrophenyl)prop-2-enone
1e. Mp 151–153 ꢀC (pet-ether); IR (KBr) vmax 3423, 2921,
1643, 1552, 1512, 1438, 1345, 1055, 898, 860, 797; H
1
NMR (300 MHz, CDCl3, TMS) d 2.90 (3H, br s), 3.25 (3H,
br s), 5.61 (1H, d, J¼12.8 Hz), 7.78 (1H, d, J¼12.1 Hz),
7.95 (2H, d, J¼8.5 Hz), 8.22 (2H, d, J¼8.5 Hz); 13C NMR
(50 MHz, CDCl3) d 37.2, 45.1, 91.7, 123.2, 128.1, 145.9,
148.8, 155.0, 185.8; MS (EI) m/z 220 (M+, 32%), 204 (82),
157 (10), 70 (25), 55 (22), 44 (7). Anal. Calcd for
C11H12N2O3: C, 59.99; H, 5.49; N, 12.72. Found: C, 59.86;
H, 5.56; N, 12.80.
3.3. Representative procedure for the preparation of 1a–g
To a mixture of 4-nitroacetophenone (3.30 g, 20 mmol), in
xylene (100 mL), was added dimethylformamide dimethyl-
acetal (2.38 g, 20 mmol) and the reaction refluxed for 7 h
(monitored by TLC). The xylene was distilled off and the
3.3.6. 3-Dimethylamino-1-(4-methoxyphenyl)prop-2-
enone 1f. Yield 83%, mp 98–100 ꢀC (pet-ether, lit.10

13028
S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
100 ꢀC); IR (KBr) vmax 2906, 2803, 1639, 1581, 1541, 1431,
1357, 1304, 1246, 1174, 1114, 1055, 1024, 902, 842, 772; 1H
NMR (300 MHz, CDCl3, TMS) d 3.01 (6H, br s), 3.85 (3H,
s), 5.65 (1H, d, J¼12.4 Hz), 6.85 (2H, d, J¼8.8 Hz), 7.70
(1H, d, J¼12.4 Hz), 7.85 (2H, d, J¼8.8 Hz); MS (EI) m/z
205 (M+, 46%), 188 (100), 162 (8), 135 (50), 98 (97), 92
(25). Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37; N,
6.82. Found: C, 70.09; H, 7.28; N, 6.87.
J¼7.5 Hz), 7.22 (2H, d, J¼7.5 Hz), 7.56 (1H, d, J¼8.3 Hz),
7.95 (2H, d, J¼8.3 Hz), 8.20 (1H, d, J¼8.3 Hz); 13C NMR
(50 MHz, CDCl3) d 14.2, 21.2, 25.1, 60.9, 116.8, 123.2,
127.0, 129.4, 135.6, 139.0, 139.6, 158.9, 159.7, 166.5; MS
(EI) m/z 255 (M+, 100%), 210 (93), 183 (25), 167 (26), 129
(11), 115 (27), 91 (26), 63 (25). Anal. Calcd for
C16H17NO2: C, 75.27; H, 6.71; N, 5.49. Found: C, 75.19;
H, 6.78; N, 5.55.
3.3.7. 3-Dimethylamino-1-(1-naphthyl)prop-2-enone 1g.
Yield 89% (flash column chromatography on SiO2, eluting
with light petroleum–EtOAc (1:1), gave compound 1g as
a pale yellow oil); IR (KBr) vmax 3446, 3051, 2922, 1641,
1555, 1423, 1349, 1273, 1094, 986, 900, 738, 627; 1H
NMR (300 MHz, CDCl3, TMS) d 2.80–3.20 (6H, br 2 s),
5.46 (1H, d, J¼12.8 Hz), 7.40–7.58 (5H, m), 7.80 (2H, m),
8.24 (1H, d, J¼9.0 Hz); MS (EI) m/z 225 (M+, 6%), 169
(25), 141 (100), 125 (10), 115 (7), 105 (33), 83 (10), 57
(22), 43 (53). Anal. Calcd for C15H15NO: C, 79.97; H,
6.71; N, 6.22. Found: C, 79.86; H, 6.69; N, 6.30.
3.4.3. Ethyl (2-methyl-6-p-chlorophenyl)nicotinate 3c.
Yield 96%, mp 74–75 ꢀC (MeOH, lit.11 74–75 ꢀC) IR
(KBr) vmax 2979, 2929, 1723, 1583, 1450, 1269, 1094,
1
1012, 827, 778; H NMR (300 MHz, CDCl3, TMS) d 1.42
(3H, t, J¼7.1 Hz), 2.88 (3H, s), 4.37 (2H, q, J¼7.1 Hz),
7.40 (2H, d, J¼8.6 Hz), 7.55 (1H, d, J¼8.1 Hz), 8.00 (2H,
d, J¼8.6 Hz), 8.20 (1H, d, J¼8.1 Hz); MS (EI) m/z 275
(M+, 71%), 247 (25), 230 (100), 203 (38), 167 (62), 141
(47), 115 (47), 75 (47), 63 (40). Anal. Calcd for
C15H14ClNO2: C, 65.34; H, 5.12; N, 5.08. Found: C,
65.27; H, 5.17; N, 5.17.
3.4. Representative procedure for the preparation of 3a–g
3.4.4. Ethyl (2-methyl-6-p-bromophenyl)nicotinate 3d.
Yield 97%, mp 73–75 ꢀC (MeOH, lit.11 72–74 ꢀC) IR (KBr)
vmax 2978, 2929, 1721, 1582, 1451, 1369, 1267, 1089,
To a mixture of 3-dimethylamino-1-(4-nitrophenyl)prop-
2-enone 1e (0.550 g, 2.5 mmol), ethyl acetoacetate 2a
(0.325 g, 2.5 mmol), ammonium acetate (0.385 g, 5 mmol)
in 5 mL of isopropanol (Method A) was added K5CoW12-
O40$3H2O (0.080 g, 0.025 mmol, 1.0 mol %) and refluxed
for 120 min (monitored by TLC). The resulting mixture
was cooled to room temperature, the catalyst filtered off
and washed with 5 mL of hot isopropanol. The IPA solution
was concentrated on rotary evaporator and then recrystal-
lized in methanol to afford pure product 3e as pale yellowish
solid (0.650 g, 91%). In solvent free conditions (Method B)
the reaction mixture was stirred and heated at 115 ꢀC for
30 min and the progress of the reaction was monitored by
TLC. After completion, 5 mL of hot methanol was added
to the reaction mixture; the catalyst was filtered off and
washed with another 5 mL of hot methanol. The methanol
solution was then cooled to afford pure product 3e as pale
yellowish solid (0.700 g, 98%). The filtered catalyst was
reactivated by heating at 80 ꢀC for 2 h and reused at least
five times.
1
1009, 826, 779; H NMR (300 MHz, CDCl3, TMS) d 1.44
(3H, t, J¼6.8 Hz), 2.89 (3H, s), 4.36 (2H, q, J¼6.8 Hz),
7.55 (3H, m), 7.93 (2H, d, J¼7.5 Hz), 8.20 (1H, d,
J¼8.3 Hz); MS (EI) m/z 319 (M+, 96%), 317 (100), 275
(16), 275 (64), 274 (66), 249 (47), 247 (54), 182 (25), 167
(77), 155 (21), 141 (41), 126 (11), 115 (9), 83 (13), 75 (15),
63 (11), 39 (14). Anal. Calcd for C15H14BrNO2: C, 56.27;
H, 4.41; N, 4.37. Found: C, 56.31; H, 4.30; N, 4.31.
3.4.5. Ethyl (2-methyl-6-p-nitrophenyl)nicotinate 3e. Mp
11
142 ꢀC (MeOH, lit. 71–73 ꢀC); IR (KBr) vmax 3094,
2974, 2928, 2849, 1719, 1580, 1517, 1436, 1371, 1340,
1260, 1160, 1087, 847, 791, 746; 1H NMR (300 MHz,
CDCl3, TMS) d 1.45 (3H, t, J¼7.5 Hz), 2.92 (3H, s), 4.42
(2H, q, J¼7.5 Hz), 7.70 (1H, d, J¼8.3 Hz), 8.22–8.37 (5H,
m); 13C NMR (50 MHz, CDCl3) d 14.2, 25.0, 61.3, 117.9,
123.8, 125.0, 127.9, 139.5, 144.1, 148.4, 156.0, 160.2,
166.1; MS (EI) m/z 286 (M+, 100%), 242 (88), 207 (55),
178 (27), 150 (91), 140 (26), 104 (32), 75 (28), 43 (60).
Anal. Calcd for C15H14N2O4: C, 62.93; H, 4.93; N, 9.79.
Found: C, 63.08; H, 4.86; N, 9.88.
3.4.1. Ethyl (2-methyl-6-phenyl)nicotinate 3a. Yield 95%,
mp 43–45 ꢀC (MeOH, lit.11 43–45 ꢀC); IR (KBr) vmax 2991,
2928, 1715, 1581, 1451, 1269, 1088, 758, 691; H NMR
1
3.4.6. Ethyl (2-methyl-6-p-methoxyphenyl)nicotinate 3f.
Yield 92%, mp 48–50 ꢀC (MeOH, lit.11 68–69 ꢀC); IR
(KBr) vmax 3094, 2978, 2931, 2837, 1716, 1678, 1581,
1560, 1508, 1455, 1386, 1250, 1178, 1092, 1032, 828,
783; 1H NMR (300 MHz, CDCl3, TMS) d 1.40 (3H,
t, J¼7.5 Hz), 2.89 (3H, s), 3.82 (3H, s), 4.35 (2H,
q, J¼7.5 Hz), 6.92 (2H, d, J¼9.0 Hz), 7.50 (1H, d,
J¼8.3 Hz), 8.0 (2H, d, J¼9.0 Hz), 8.19 (1H, d, J¼8.3 Hz);
MS (EI) m/z 271 (M+, 100%), 244 (17), 227 (51), 200 (6),
150 (10), 136 (32), 105 (7), 77 (22), 63 (15). Anal. Calcd
for C16H17NO3: C, 70.83; H, 6.32; N, 5.16. Found: C,
70.76; H, 6.39; N, 5.09.
(300 MHz, CDCl3, TMS) d 1.42 (3H, t, J¼7.1 Hz), 2.92
(3H, s), 4.38 (2H, q, J¼7.1 Hz), 7.42 (3H, m), 7.60 (1H, d,
J¼8.1 Hz), 8.05 (2H, m), 8.22 (1H, d, J¼8.3 Hz); 13C
NMR (50 MHz, CDCl3) d 14.1, 25.1, 60.9, 117.1, 123.5,
127.2, 128.6, 129.5, 138.4, 139.1, 158.9, 159.8, 166.5; MS
(EI) m/z 241 (M+, 100%), 213 (26), 196 (93), 169 (32),
155 (12), 141 (57), 128 (26), 115 (70), 98 (22), 84 (20),
77 (26), 57 (12), 51 (15). Anal. Calcd for C15H15NO2:
C, 74.67; H, 6.27; N, 5.81. Found: C, 74.59; H, 6.31;
N, 5.93.
3.4.2. Ethyl (2-methyl-6-p-methylphenyl)nicotinate 3b.
Yield 93%, mp 53–55 ꢀC (MeOH, lit.11 53–54 ꢀC) IR
(KBr) vmax 2983, 2928, 1714, 1581, 1451, 1269, 1184,
1090, 824, 780; H NMR (300 MHz, CDCl3, TMS) d 1.41
(3H, t, J¼7.5 Hz), 2.40 (3H, s), 2.88 (3H, s), 4.38 (2H, q,
3.4.7. Ethyl (2-methyl-6-1-naphthyl)nicotinate 3g. Yield
94% (flash column chromatography on SiO2, eluting with
light petroleum–EtOAc (9:1), gave compound 3g as a pale
yellow oil); IR (film) vmax 3052, 2979, 2931, 1721, 1584,
1

S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
13029
1
1556, 1508, 1445, 1390, 1269, 1148, 1081, 858, 782, 740; 1H
NMR (300 MHz, CDCl3, TMS) d 1.45 (3H, t, J¼7.0 Hz),
2.98 (3H, s), 4.35 (2H, q, J¼7.0 Hz), 7.42–7.65 (5H, m),
7.82–8.15 (3H, m), 8.32 (1H, d, J¼8.5 Hz); MS (EI) m/z
291 (M+, 11%), 263 (43), 219 (20), 128 (40), 113 (13),
105 (80), 86 (11), 77 (65), 58 (222), 44 (100). Anal. Calcd
for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C,
78.27; H, 5.78; N, 4.90.
952, 816, 762; H NMR (300 MHz, CDCl3, TMS) d 2.62
(3H, s), 2.86 (3H, s), 7.62 (3H, m), 7.96–8.10 (3H, m); 13C
NMR (50 MHz, CDCl3) d 25.1, 29.1, 116.8, 124.2, 128.6,
130.8, 131.8, 137.0, 137.8, 157.1, 158.4, 199.6; MS (EI)
m/z 289 (M+, 20%), 273 (35), 247 (100), 221 (17), 182
(15), 167 (57), 141 (37), 101 (61), 75 (88), 43 (83). Anal.
Calcd for C14H12BrNO: C, 57.95; H, 4.17; N, 4.83. Found:
C, 57.88; H, 4.23; N, 4.90.
3.5. Representative procedure for the preparation of 4a–g
3.5.5. 1-(2-Methyl-6-p-nitrophenylpyridin-3-yl)ethanone
4e. Mp 131 ꢀC (MeOH); IR (KBr) vmax 2925, 2851, 1719,
1682, 1581, 1517, 1428, 1341, 1261, 830, 739; H NMR
1
To a mixture of 3-dimethylamino-1-(4-nitrophenyl)-prop-2-
en-1-one 1e (0.550 g, 2.5 mmol), acetyl acetone 2b (0.250 g,
2.5 mmol), ammonium acetate (0.385 g, 5 mmol) in isopro-
panol (5 mL) (Method A) was added K5CoW12O40$3H2O
(0.080 g, 0.025 mmol, 1.0 mol %) and refluxed for
120 min (monitored by TLC). The reaction mixture was
worked up as represented above to yield product 4e as pale
yellowish solid (0.576 g, 90%). In solvent free conditions
(Method B) the reaction mixture was stirred and heated at
115 ꢀC for 30 min (monitored by TLC) and worked up as
represented in the above procedure to afford pure pale yel-
low product 4e (0.620 g, 97%).
(300 MHz, CDCl3, TMS) d 2.62 (3H, s), 2.82 (3H, s), 7.72
(1H, d, J¼7.5 Hz), 8.08 (1H, d, J¼7.5 Hz), 8.25 (2H, d,
J¼9.0 Hz), 8.30 (2H, d, J¼9.0 Hz); 13C NMR (50 MHz,
CDCl3) d 25.0, 29.3, 117.9, 123.9, 128.0, 131.9, 137.9,
144.0, 148.4, 155.6, 158.7, 199.7; MS (EI) m/z 256 (M+,
7%), 241 (25), 167 (8), 148(9), 115 (8), 105 (100), 91 (32),
77 (80), 51 (44), 43 (54). Anal. Calcd for C14H12N2O3:
C, 65.62; H, 4.72; N, 10.93. Found: C, 65.69; H, 4.66; N,
10.87.
3.5.6. 1-(2-Methyl-6-p-methoxyphenylpyridin-3-yl)etha-
none 4f. Yield 86%, mp 100 ꢀC (MeOH); IR (KBr) vmax
2926, 2850, 1683, 1605, 1575, 1510, 1454, 1253, 1174,
3.5.1. 1-(2-Methyl-6-phenylpyridin-3-yl)ethanone 4a.
Yield 93%, mp 110 ꢀC (MeOH, lit.11 110 ꢀC); IR (KBr)
vmax 2930, 1679, 1575, 1422, 1351, 1254, 742, 689; H
1
1026, 826, 792; H NMR (300 MHz, CDCl3, TMS) d 2.60
1
(3H, s), 2.72 (3H, s), 3.88 (3H, s), 6.95 (2H, d, J¼9.0 Hz),
7.55 (1H, d, J¼8.3 Hz), 7.95–8.05 (3H, m); 13C NMR
(50 MHz, CDCl3) d 25.3, 29.1, 55.3, 114.2, 116.2, 128.8,
128.2, 129.9, 131.0, 137.9, 158.6, 161.1, 199.7; MS (EI)
m/z 241 (M+, 43%), 226 (53), 199 (100), 184 (32), 156
(42), 141 (40), 128 (8), 43 (15). Anal. Calcd for
C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.59;
H, 6.31; N, 5.79.
NMR (300 MHz, CDCl3, TMS) d 2.58 (3H, s), 2.82 (3H,
s), 7.36–7.50 (3H, m), 7.62 (1H, d, J¼8.3 Hz), 8.01–8.10
(3H, m); 13C NMR (50 MHz, CDCl3) d 25.2, 29.1, 117.1,
127.2, 128.7, 129.6, 137.8, 138.3, 158.4, 158.5, 199.8; MS
(EI) m/z 211 (M+, 60%), 196 (100), 168 (40), 153 (10),
141 (57), 115 (15), 77 (11), 43 (20). Anal. Calcd for
C14H13NO: C, 79.59; H, 6.20; N, 6.63. Found: C, 79.48;
H, 6.19; N, 6.71.
3.5.7. 1-(2-Methyl-6–1-naphthylpyridin-3-yl)ethanone
4g. Yield 93% (flash column chromatography on SiO2, elut-
ing with light petroleum, gave compound 4g as a pale yellow
oil); IR (film) vmax 3054, 2924, 2852, 1685, 1585, 1580, 1553,
1433, 1353, 1260, 952, 801, 779; 1H NMR (300 MHz,
CDCl3, TMS) d 2.62 (3H, s), 2.85 (3H, s), 7.42–8.10 (9H,
m); 13C NMR (50 MHz, CDCl3) d 24.9, 29.3, 122.0, 124.4,
125.2, 125.3, 125.9, 126.5, 127.5, 128.3, 129.3, 130.9,
133.9, 137.2, 137.5, 158.1, 160.8, 200.1; MS (EI) m/z 261
(M+, 100%), 247 (13), 204 (8), 190 (12), 177 (7), 156 (13),
142 (31), 128 (25), 110 (13), 77 (21), 58 (25), 44 (66).
Anal. Calcd for C18H15NO: C, 82.73; H, 5.79; N, 5.36. Found:
C, 82.64; H, 5.81; N, 5.41.
3.5.2. 1-(2-Methyl-6-p-methylphenylpyridin-3-yl)etha-
none 4b. Yield 90%, mp 82–84 ꢀC (MeOH); IR (KBr) vmax
2921, 1681, 1578, 1451, 1260, 1184, 818, 788, 763; H
1
NMR (200 MHz, CDCl3, TMS) d 2.45 (3H, s), 2.60 (3H,
s), 2.85 (3H, s), 7.28 (2H, d, J¼7.8 Hz), 7.60 (1H, d,
J¼7.8 Hz), 7.95–8.05 (3H, m); 13C NMR (50 MHz, CDCl3)
d 21.2, 25.2, 29.1, 116.7, 117.4, 126.7, 127.1, 128.3, 129.4,
137.8, 138.0, 158.5, 199.7; MS (EI) m/z 225 (M+, 8%), 210
(7), 197 (46), 183 (100), 167 (19), 115 (13), 91 (33), 39
(42). Anal. Calcd for C15H15NO: C, 79.97; H, 6.71; N,
6.22. Found: C, 79.91; H, 6.80; N, 6.31.
3.5.3. 1-(2-Methyl-6-p-chlorophenylpyridin-3-yl)etha-
none 4c. Yield 95%, mp 58–60 ꢀC (MeOH); IR (KBr)
vmax 3077, 2994, 2967, 2925, 1677, 1577, 1488, 1430,
1351, 1260, 1180, 1089, 816, 763, 628; 1H NMR
(300 MHz, CDCl3, TMS) d 2.58 (3H, s), 2.82 (3H, s), 7.40
(2H, d, J¼8.6 Hz), 7.58 (1H, d, J¼7.7 Hz), 7.98–8.14 (3H,
m); 13C NMR (50 MHz, CDCl3) d 25.1, 29.0, 116.7,
128.3, 128.8, 130.7, 136.5, 137.8, 157.0, 158.4, 158.5,
199.5; MS (EI) m/z 245 (M+, 56%), 230 (100), 202 (11),
167 (23). Anal. Calcd for C14H12ClNO: C, 68.44; H, 4.92;
N, 5.70. Found: C, 68.39; H, 4.85; N, 5.81.
3.6. Representative procedure for the preparation of 5a–g
To a mixture of 3-dimethylamino-1-(4-nitrophenyl)-prop-2-
enone 1e (0.550 g, 2.5 mmol), dimedone 2c (0.350 g,
2.5 mmol), ammonium acetate (0.385 g, 5 mmol) in isopro-
panol (5 mL) (Method A) was added K5CoW12O40$3H2O
(0.080 g, 0.025 mmol, 1.0 mol %) and refluxed for 120 min
(monitored by TLC). The resulting mixture was worked out
as described above to obtain pure 5e as pale yellow com-
pound (0.688 g, 93%). In solvent free conditions (Method
B) the reaction mixture was stirred and heated at 115 ꢀC
for 45 min (monitored by TLC) and worked out as repre-
sented in the above procedure to afford pure pale yellow
product 5e (0.725 g, 98%).
3.5.4. 1-(2-Methyl-6-p-bromophenylpyridin-3-yl)etha-
none 4d. Yield 96%, mp 76–78 ꢀC (MeOH); IR (KBr)
vmax 2925, 1678, 1576, 1485, 1430, 1352, 1256, 1005,

13030
S. Kantevari et al. / Tetrahedron 63 (2007) 13024–13031
3.6.1. 7,7-Dimethyl-5-oxo-2-(phenyl)-5,6,7,8-tetrahydro-
quinoline 5a. Yield 94%, mp 65–67 ꢀC (MeOH); IR (KBr)
vmax 3059, 2950, 2867, 1678, 1581, 1446, 1395, 1304,
150 (100), 141 (20), 104 (73), 76 (31), 43 (100). Anal. Calcd
for C17H16N2O3: C, 68.90; H, 5.44; N, 9.45. Found: C,
68.99; H, 5.36; N, 9.50.
1
1186, 1122, 837, 778; H NMR (300 MHz, CDCl3, TMS)
d 1.15 (6H, s), 2.02 (2H, s), 3.08 (2H, s), 7.49 (3H, m),
7.70 (1H, d, J¼7.5 Hz), 8.05 (2H, m), 8.26 (1H, d,
J¼8.3 Hz); 13C NMR (50 MHz, CDCl3) d 25.2, 28.0, 32.6,
46.4, 51.7, 118.4, 125.2, 127.1, 128.5, 129.6, 136.7, 138.1,
160.6, 162.0, 197.3; MS (EI) m/z 251 (M+, 76%), 236
(12), 223 (23), 208 (7), 195 (100), 167 (28), 141 (23), 77
(10). Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N,
5.57. Found: C, 81.19; H, 6.79; N, 5.66.
3.6.6. 7,7-Dimethyl-5-oxo-2-(4-methoxyphenyl)-5,6,7,8-
tetrahydroquinoline 5f. Yield 90%, mp 125 ꢀC (MeOH);
IR (KBr) vmax 3071, 2959, 2932, 2840, 1676, 1580, 1510,
1
1447, 1307, 1254, 1173, 1028, 830, 809, 759; H NMR
(300 MHz, CDCl3, TMS) d 1.15 (6H, s), 2.52 (2H, s), 3.05
(2H, s), 3.90 (3H, s), 6.95 (2H, d, J¼8.7 Hz), 7.65 (1H, d,
J¼8.0 Hz), 8.05 (2H, d, J¼8.7 Hz), 8.25 (1H, d, J¼8.0 Hz);
13C NMR (50 MHz, CDCl3) d 28.2, 32.8, 46.6, 51.9, 55.2,
113.5, 114.1, 117.7, 124.8, 128.7, 130.4, 130.8, 135.0,
161.2, 162.2, 197.6; MS (EI) m/z 281 (M+, 100%), 267 (6),
254 (8), 239 (8), 226 (61), 183 (11), 151 (28), 136 (95),
128 (22), 109 (10), 105 (10), 89 (35), 77 (44), 52 (35), 42
(55). Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N,
4.98. Found: C, 76.73; H, 6.88; N, 5.01.
3.6.2. 7,7-Dimethyl-5-oxo-2-(4-methylphenyl)-5,6,7,8-
tetrahydroquinoline 5b. Yield 91%, mp 120 ꢀC (MeOH);
IR (KBr) vmax 3028, 2951, 2926, 2868, 1676, 1581, 1448,
1
1387, 1303, 1180, 802, 757; H NMR (300 MHz, CDCl3,
TMS) d 1.15 (6H, s), 2.42 (3H, s), 2.53 (2H, s), 3.10 (2H,
s), 7.25 (2H, d, J¼7.9 Hz), 7.65 (1H, d, J¼8.3 Hz), 7.95
(2H, d, J¼8.3 Hz), 8.25 (1H, d, J¼8.3 Hz); 13C NMR
(50 MHz, CDCl3) d 21.1, 28.1, 32.7, 46.5, 51.9, 119.2,
125.1, 127.1, 129.9, 135.0, 139.9, 150.8, 160.8, 162.1,
197.5; MS (EI) m/z 265 (M+, 40%), 236 (7), 209 (43), 181
(87), 154 (36), 140 (100), 71 (7), 43 (22). Anal. Calcd for
C18H19NO: C, 81.47; H, 7.22; N, 5.28. Found: C, 81.39;
H, 7.29; N, 5.31.
3.6.7. 7,7-Dimethyl-5-oxo-2-(1-naphthyl)-5,6,7,8-tetrahy-
droquinoline 5g. Yield 95% (flash column chromatography
on SiO2, eluting with light petroleum, gave compound 5g
as pale yellow oil); IR (film) vmax 3053, 2956, 2870,
1729, 1686, 1581, 1560, 1508, 1396, 1305, 1115, 848,
1
801, 778, 741, 663; H NMR (300 MHz, CDCl3, TMS)
d 1.20 (6H, s), 2.60 (2H, s), 3.15 (2H, s), 7.45–7.65 (5H,
m), 7.85–7.95 (2H, m), 8.10 (1H, m), 835 (1H, d,
J¼8.3 Hz); 13C NMR (50 MHz, CDCl3) d 28.2, 32.9,
46.5, 52.0, 123.5, 125.1, 125.2, 125.4, 125.9, 126.6,
127.7, 128.4, 129.5, 130.7, 133.9, 134.8, 137.5, 162.1,
163.3, 197.8; MS (EI) m/z 301 (M+, 38%), 217 (11), 171
(16), 156 (50), 138 (11), 128 (71), 118 (57), 106 (46), 89
(27), 66 (51), 64 (93), 42 (100). Anal. Calcd for
C21H19NO: C, 83.69; H, 6.35; N, 4.65. Found: C, 83.61;
H, 6.41; N, 4.71.
3.6.3. 7,7-Dimethyl-5-oxo-2-(4-chlorophenyl)-5,6,7,8-tet-
rahydroquinoline 5c. Yield 97%, mp 105 ꢀC (MeOH); IR
(KBr) vmax 2954, 2929, 2867, 1683, 1576, 1416, 1300,
1
1090, 829, 807, 753; H NMR (300 MHz, CDCl3, TMS)
d 1.15 (6H, s), 2.52 (2H, s), 3.05 (2H, s), 7.42 (2H, d,
J¼8.6 Hz), 7.65 (1H, d, J¼8.3 Hz), 8.0 (2H, d, J¼8.8 Hz),
8.28 (1H, d, J¼8.1 Hz); 13C NMR (50 MHz, CDCl3)
d 28.1, 32.8, 46.5, 51.9, 118.3, 125.6, 128.9, 129.5, 131.1,
135.3, 136.0, 136.6, 159.5, 162.3, 197.5; MS (EI) m/z 285
(M+, 27%), 284 (25), 283 (82), 256 (31), 229 (100), 200
(17), 166 (95), 138 (32), 102 (20), 55 (31), 63 (37). Anal.
Calcd for C17H16ClNO: C, 71.45; H, 5.64; N, 4.90. Found:
C, 71.39; H, 5.59; N, 4.99.
Supplementary data
1H NMR, 13C NMR, EIMS, spectra for enaminones 1a–g,
2,3,6-trisubstituted pyridines 3a–g and 4a–g, tetrahydroqui-
noline-5-ones 5a–g. Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2007.10.014.
3.6.4. 7,7-Dimethyl-5-oxo-2-(4-bromophenyl)-5,6,7,8-tet-
rahydroquinoline 5d. Yield 96%, mp 132 ꢀC (MeOH); IR
(KBr) vmax 2953, 2928, 2867, 1678, 1574, 1413, 1378,
1299, 1070, 1008, 828, 806, 743; 1H NMR (300 MHz,
CDCl3, TMS) d 1.16 (6H, s), 2.52 (2H, s), 3.08 (2H, s),
7.59 (2H, d, J¼9.0 Hz), 7.66 (1H, d, J¼8.3 Hz), 7.95 (2H,
d, J¼8.3 Hz), 8.28 (1H, d, J¼8.3 Hz); 13C NMR (50 MHz,
CDCl3) d 28.1, 32.8, 46.5, 51.9, 118.3, 124.5, 125.6,
128.8, 129.6, 131.8, 135.3, 137.1, 159.5, 162.3, 197.5; MS
(EI) m/z 329 (M+, 96%), 300 (18), 273 (93), 191 (8), 166
(100), 139 (32), 102 (26), 75 (28), 39 (95). Anal. Calcd for
C17H16BrNO: C, 61.83; H, 4.88; N, 4.24. Found: C, 61.77;
H, 4.91; N, 4.31.
References and notes
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cited therein; (b) Bagley, M. C.; Chapaneri, K.; Dale, D. W.;
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3076, 2928, 2870, 1688, 1575, 1515, 1419, 1344, 835,
1
732; H NMR (300 MHz, CDCl3, TMS) d 1.18 (6H, s),
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