Simple and efficient one-pot synthesis of 3,4-dihydro-2-pyridones via solid-supported Bi(III)nitrate catalyzed double Michael addition-azaannulation

Article abstract of DOI:10.1002/jhet.5570450209

(Chemical Equation Presented) 4-Aryl-5-carboethoxy-6-methyl-2,3-dihydro-2- pyridones were obtained, in high yield, by heating ternary mixtures of appropriate aldehydes, ethylacetoacetate and compounds possessing NH ₂-C=X functionality, in prese

Full text of DOI:10.1002/jhet.5570450209

Mar-Apr 2008
349
Simple andEfficient One-pot Synthesis of 3,4-Dihydro-2-pyridones via
Solid-Supported Bi(III)nitrate catalyzed Double Michael Addition-
Azaannulation
Jagjeet Singh 1, Summon Koul 1, 1a, Ajay P. S. Pannu 2, Rattan L. Sharma 1 and Tej K. Razdan *1
1Department of Chemistry, University of Jammu, Ambedkar Road, Jammu-180006, India.
1a Present address : Advinus Therapeutics, International Bio-Tech Park, Genesis Squre, Hinjewadi, Pune-411057
2Department of Chemistry, G. N. D. University, Amritsar, Punjab 154003, India.
Received March 29, 2007
R1
R1
O
Bi(NO3)3-ZnCl2-Al2O3
(10%, 5% w/w), !, 140± 5 °C
R4
R4
O
R2
R3
R4
O
R2
O
O
+
+
H2N
NH2
OEt
R1
R3
R3
H
+
R2
O
EtO
EtO
N
N
H
O
N
H
O
4-Aryl-5-carboethoxy-6-methyl-2,3-dihydro-2-pyridones were obtained, in high yield, by heating ternary
mixtures of appropriate aldehydes, ethylacetoacetate and compounds possessing NH2-C=X functionality, in
presence of immobilized Bi(III)nitrate and co-catalyst Zn(II)chloride, under solventless conditions. The
reaction proceeds smoothly at 140±5°C and seems to involve double Michael addition-azaannulation.
J. Heterocyclic Chem., 45, 349 (2008).
efficient, one-pot solid-supported straight forward and
environmentally benign synthesis of these products
from aryl aldehydes, using catalyst Bi (III) nitrate,
immobilized on neutral alumina, in the presence of co-
catalyst Zn (II) chloride.
INTRODUCTION
2-Pyridones and their partially or fully reduced forms
constitute the core nucleus of several naturally occurring
products [1]. The compounds derived from these nuclei
exhibit a wide spectrum of pharmacodynamic properties,
such as anti-microbial [2], antifungal [3], and angiotensin
converting enzyme inhibiting [4] properties. Some of the
compounds inhibit DNA enzymes [5] and a few other
products have become potential candidates for anti-tumor
[6] and anti-viral [7] therapy. A majority of these products
are useful psychotherapeutic agents [8]. Therefore, the
synthesis of 2-pyridone derivatives continues to be a
subject of great interest. Several methodologies [9],
mostly involving oxidation of pyridinium salts [10],
Dieckmann-like [11] and Knoevengel’s, reactions [12],
have been documented for the synthesis of 2-pyridones.
Most of these methodologies suffer with one or the other
drawback, such as multi-step laborious processes,
involvement of stringent or environmentally hazardous
reaction conditions, expensive rare-earth catalysts,
sometimes in stoichiometric amounts, and low to
moderate yield of products. Furthermore, little attention
has been paid to the direct synthesis of dihydro-2-
pyridone derivatives. This together with our interest in the
exploration of the catalyst potential of the readily
available, inexpensive, biocompatible and non-toxic
Bi(III) nitrate in the synthesis of nitrogen heterocycles
prompted us to undertake the synthesis of 3,4-dihydro-
2-pyridones, using Bi(III) nitrate immobilized on
neutral alumina as catalyst. Herein, we report an
RESULTS AND DISCUSSION
4-Aryl-5-carboethoxy-6-methyl-3,4-dihydro-2-pyridones
were synthesized from appropriate aryl aldehyde 1a-1m,
ethylacetoacetate 2 and urea 3a, in the presence of the
catalyst Bi(III) nitrate, immobilized on neutral alumina,
and co-catalyst Zn(II) chloride. Earlier [13], Bi(III)
nitrate, immobilized on alumina, has been found to
efficiently catalyze the Michael addition under solventless
conditions. This led us to presume that in the presence of
immobilized Bi(III) nitrate an aldehyde and ethyl-
acetoacetate (1:2 moles) may form 1,5-diketones, via
aldol condensation and Michael addition, which on
subsequent regiospecific, aza-annulation may lead to
target compounds. However, this hypothesis failed when
ternary mixtures of arylaldehydes, ethylacetoacetate, urea
(1:2:1 mole) and the catalyst 10% (w/w) Bi(III) nitrate on
Al2O3, were heated, at 140 ± 5°C, under solvent less
conditions. These reactions afforded mainly 4-aryl-5-
carboethoxy-6-methyl-1,4-dihydropyrimidones [11].
Therefore, it occurred to us that it may be possible to
divert the preferential Michael addition with urea by
catalyst manipulation, using a co-catalyst with relatively
higher activity than Bi(III) nitrate. Since, our primary goal
has been to make use of inexpensive and biocompatible

350
J. Singh, S. Koul, A. P. S. Pannu, R. L. Sharma and T. K. Razdan
Vol 45
1
metal salts, we chose Zn(II) chloride as co-catalyst. The
catalyst was prepared by adsorbing Bi(III) nitrate (10%
w/w) on neutral alumina and impregnating the activated
Bi(III) nitrate-Al2O3 mixture, with co-catalyst Zn(II)
chloride (5% w/w). The heterocatalyst mixture was
activated, at 110 ± 5 °C, for 4 hours, in a thermostatically
controlled hot-air oven. The catalyst mixture was
reactivated at the same temperature, each time before use.
Compounds 4a-4m were obtained by heating, at 140 ±
5 °C, the ternary mixtures of aryl aldehyde 1a-1m,
ethylacetoacetate 2 and urea 3a (1:2:1 mole) in the
presence of the heterocatalyst mixture Bi(III) nitrate-
Al2O3-Zn(II) chloride, in proportion of the mass of
substrates (calc. conc. of Bi(III) and Zn(II) ions approx. 5
mol. % and 2.5 mol. %), in thermostatically controlled
hot-air oven. The reaction was monitored by tlc of the
chloroform extract of the aliquots drawn out, from a
simultaneously run separate experimental vessel, at 0.5
hour intervals. On completion of the reaction (4-5 hrs),
the products were isolated with hot chloroform, the
solvent was removed and the compounds were purified by
column chromatography on silica gel, using graded
solvent systems. Two products 4a-4m (52-69%) and 5a-
5m (21-40%) were obtained (Table 1). The products were
The H-NMR spectra of 4a-4m displayed characteristic
resonance signals at
δ 1.16 (t, J=7.0 Hz, 3H,
CO2CH2CH3), 2.23 (s, 3H, =C-CH3), 2.30 (dd, J=14.2, 3.2
Hz, 2H, H-3), 4.01 (q, J=7.0 Hz, CO2CH2), 4.23 (d, J=3.2
Hz, H-4), 5.26 (s br, 1H, NH), besides the expected
aromatic proton signals. The 13C-NMR signals were
assigned on the basis of DEPT 135°. The mass fragmen-
tation was consistent with the assigned structures, with
molecular ion peak as the base peak and major peaks
arising out of loss of ethyl radical, carbon monoxide and
arylimine.
The structures of 4a-4m were further confirmed by the
X-ray analysis of 4e, as a representative compound, and
comparison of their spectral data with 4e. Compound 4e
crystallized in triclinic forms with cell dimensions: a =
7.685 Å, b = 8.232 Å, c = 11.846 Å and α = 92.8, β =
100.1, γ = 108.5 (Table 3). The ORTEP diagram of 4e is
given in Fig. 1 the X-ray data of the compound has been
tabulated in Table 3-6. The 2-pyridone nucleus assumes a
quasi chair conformation with bond angles C2-C1-N1
115.7, C1-C2-C3, 127.1; C2-C3-C4; 190.0° and C4-C5-N1,
120.4°.
To generalize this reaction we carried out the reactions
of aldehydes 1a-1m, ethylacetoacetate 2 and the catalyst
mixture with acetamide 3b, benzamide 3c, buiret 3d and
semicarbazide 3e, at 140 ± 5°C. Except for the reaction
with 3e, which yielded multi-component mixtures and
were not analyzed, all other reactions afforded mainly
3,4-dihydro-2-pyridones (62-82%) (Table 2). The reaction
with 3c also formed benzoic acid as a minor product.
1
analyzed by spectral methods viz. HRMS, IR, H-NMR,
13C-NMR and DEPT-135°. The products 5a-5m were
found to be 4-aryl-5-carboethoxy-6-methyl-1,4-dihydro-
pyrimidones and their identity was further confirmed by
their co-tlc and mixed mp, with the authentic samples
available to us, and the literature [11].
Scheme I
R1
R1
R4
O
R2
R3
R4
O
R2
O
R4
R1
O
R3
H
O
Bi(NO3)3-ZnCl2-Al2O3
(10%, 5% w/w), , 140± 5 °C
+
+
!
EtO
H2N
NH2
OEt
+
EtO
N
R3
R2
O
N
O
N
H
O
H
1a - 1m
2
3a
4a - 4m
5a - 5m
R1
1a. H
1b. OCH3
1c. Cl
R2
R3
R4
H
H
H
OCH3
H
H
Cl
H
OH
H
H
H
H
H
H
Cl
OH
OH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1d. OCH3
1e.
1f.
H
H
1g. H
1h. Br
1i. OCH3
1k. CN
1l. C5H5O
1m. NO2
H
H
H

Mar-Apr 2008 Simpleand EfficientOne-potSynthesisof 3,4-Dihydro-2-pyridonesviaSolid-Supported Bi(III)nitrate
351
Although, the exact role of co-catalyst Zn(II) chloride is
not well understood its necessity in the formation of 3,4-
dihydro-2-pyridones was evident from the fact that in its
absence, the reactions of 1a, 2 and 3, catalyzed by Bi(III)
nitrate-Al2O3, led to the formation of 4-aryl-5-carbo-
ethoxy-6-methyl-1,4-dihydropyrimidones as the main
product. Also, the same products were obtained when
ZnCl2, immobilized on neutral alumina was used as a
catalyst, in the absence of Bi(III) nitrate.
Mechanistically, the reaction of arylaldehyde,
ethylacetoacetate and compounds possessing NH2−C=X
group may be rationalized as to involve Aldol
condensation followed by Michael addition and
subsequent aza-annulation with amines (Scheme 3) to
form azetidine intermediate, on one side, and pyrimidone,
on the other. The intermediate azetidine, most probably,
undergoes Zn (II) mediated rearrangement to form
thermodynamically more stable conjugate imine.
Table 1
Percentage yield of 4a-4m and 5a-5m using urea.
Product
yield percent
Microwave
yield%
Product
yield percent
Microwave
yield %
Time
4a
4b
4c
4d
4e
4f
4g
4h
4i
66
67
65
69
58
56
58
60
58
68
52
67
66
68
72
68
74
63
64
62
60
64
71
66
64
63
10
10
12
13
15
14
13
13
12
14
15
10
14
5a
5b
5c
5d
5e
5f
5g
5h
5i
20
30
28
28
40
40
40
38
33
21
36
31
30
15
20
18
18
25
35
30
20
25
20
26
25
20
4j
4k
4l
5j
5k
5l
4m
5m
Scheme II
R1
R4
R2
R3
O
R4
R1
O
O
Bi(III)-Zn(II)-Al2O3
O
R3
O
R5
+
+
NH2
, 140 + 5oC
-
N
OEt
O
R2
1a-1m
O
H
3b-3d
4a-4m
2
( 79-88%)
Table 2
Percentage yield of 4a-4m using 3b-3d.
Compound
3b
3c
3d
4a
4b
4c
4d
4e
4f
4g
4h
4i
82
85
80
80
76
60
79
77
62
80
79
70
62
72
80
76
80
70
55
80
69
54
70
68
60
58
81
84
71
76
66
32
75
71
49
85
72
62
66
4j
4k
4l
4m

352
J. Singh, S. Koul, A. P. S. Pannu, R. L. Sharma and T. K. Razdan
Vol 45
Subsequent, conjugate addition by six-membered enolised
ester Bi(III) complex and regiospecific aza-annulation
may lead to the formation of 3-acetyl-4-aryl-5-carboeth-
oxy-6-methyl-3,4-dihydropyridine-2-one which on further
hydrolytic disproportionation via an enolate ion may form
4-aryl-5-carboethoxy-6-methyl-3,4-dihydro-pyridine-2-one.
The reaction is temperature dependent with the optimum
temperature being 140 ± 5 °C. We have also optimized the
concentration of Bi(III) nitrate and Zn(II) chloride on neutral
alumina and found that 10% (w/w) Bi(III) nitrate and
5%(w/w) Zn(II) chloride on neutral alumina showed the best
performance, when the heterocatalyst mixture was used in
proportion by weight of the substrates such that the
approximate concentration of Bi(III) nitrate and Zn(II) chloride
remained within 10 mole percent and 5 mole percent,
respectively.
Since, the application of microwave irradiation is becoming
increasingly popular in carrying out solventless thermal
Scheme III
O
OEt
R3
R2
R1
O
R3
R2
R1
Bi(III)-Zn(II)-Al2O3
O
O
O
+
Bi
!, 140± 5 °C; -H2O
R4
Michael
addition
• •
R4
OEt
NH2 R5 ; Bi(III)
(Adol)
O
EtO
R3
O
R2
Bi
O
Azaannul.
O
R2
R1
EtO
R3
-H2O
N:
R4
R1
Cat.
R5
..
N
R4
R5
O
H
O
Cat.(Rearrang)
O
O
R3 EtO
R2
O
H
O
R1
N
O
R2
EtO
R3
R5
Bi
H
EtO
O
4
OEt
R
O
O
R1
Michael add.
N
Bi
R5
R4
Azaannul
O
O
O
R2
R2
OEt
OEt
R3
R3
O
-OEt
O
R5
R1
R1
R4
N
N
R3
R4
OEt
O
O
Bi
O
OEt ; Cat.
CH -CO Et
-
3
2
O
O
R2
R2
OEt
R3
OEt
R3
+
1) H
2) Hydr.
O
R5
R1
N
R1
N
H
R4
R4
O
O
Cat.

Mar-Apr 2008 Simpleand EfficientOne-potSynthesisof 3,4-Dihydro-2-pyridonesviaSolid-Supported Bi(III)nitrate
353
Figure 1. ORTEP diagram of 4e.
Column chromatography was carried out on silica gel (Sisco
Research Lab. 60-120 mesh). TLC was done on silica gel G
(Sisco Research Lab) plates.
reactions, we repeated the reactions of 1a-1d, 2, 3a and the
catalyst in domestic microwave (4.250 MHz) using
Makhopadyay et.al’s procedure [14]. The reactions were
complete within 10-20 mins without any appreciable increase
in the percentage yield (Table 1).
Preparation of Catalyst Mixture. Bi(III) nitrate (10% w/w,
5 g) in hot MeOH-Me2CO (1:1v/v, 100 mL) was added to
neutral alumina (45 gm) and the mixture stirred for 24 hr. at
room temperature. The solvent was removed under reduced
pressure and the residue was activated at 110 ± 5°C for 8 hr., in
a thermostatically controlled hot-air oven. The activated mixture
was cooled in a desiccator. To this mixture Zn(II) chloride (5%
w/w; 2.5 g) in dry acetone (100 mL) was added and the mixture
was again stirred for 6 hrs at room temperature under anhydrous
conditions. After removing the solvent, under pressure, the
catalyst mixture was again activated at 110 ± 5°C for 10 hr. The
catalyst mixture was preserved in a desiccators and reactivated
at 110 ± 5°C, for 2 hr, each time before use.
General Procedure for the preparation of 3,4-dihydro-2-
pyridones. The aldehydes 1a-1m (1 x 10-3 moles), ethylaceto-
acetate (2 x 10-3 moles) and compounds possessing NH2-C=X, viz
urea, CH3CONH2, PhCONH2, NH2CO.NH.CONH2 and
NH2.NH.CO.NH2 (1x10-3 moles) were mixed with the catalyst, in
proportion by the mass of substrates, and stirred mechanically for
1 hr. The reaction mixture was heated at 140 ± 5 °C in a
thermostatically controlled hot-air oven. To monitor the reactions
by tlc separate experiments were simultaneously conducted.
Aliquots were drawn out at 0.5 hr intervals and reaction was
monitored by comparative tlc of the chloroform extracts, using
pet. ether-chloroform graded solvent system. On completion of the
reaction (4-5 hr) the products were isolated with hot CHCl3 in a
soxhlet extractor. The organic layer was washed with water, 1 M
We have devised a simple, straight forward, cost-
effective one-pot solventless methodology for the
preparation
of
4-aryl-5-carboethoxy-6-methyl-3,4-
dihydro-2-pyridones from aldehydes, ethylacetoacetate
and urea derivatives using a heterocatalyst mixture of
Bi(III) nitrate-Zn(II) chloride-Al2O3. The reaction seems
to proceed via a cascade sequence of reactions involving
double Michael addition and aza-annulation. The reaction
shows high functional group tolerance and does not affect
the sensitive functionalities like nitrilo and nitro group.
The added advantage of this methodology is the non-
toxicity and biocompatibility of the catalyst mixture.
EXPERIMENTAL
General. IR spectra were measured on KBr discs using a
1
Perkin Elmer R X 1-FTI R instrument. H-NMR spectra were
measured using Varian Gemini-200 (200 MHz) and JEOL-FT-
NMR-AL (300 MHz). 13C-NMR, DEPT 135° spectra were
measured on JEOL-FT-NMR-300 (75.45 MHz). HRMS were
recorded on JEOL mass spectrometer. Mp's were determined
with Metler FP-82 hot stage apparatus and are uncorrected.

354
J. Singh, S. Koul, A. P. S. Pannu, R. L. Sharma and T. K. Razdan
Vol 45
NH4OH and water. The organic layer was dried over anhyd.
Na2SO4, filtered and purified by column chromatography, using
pet. ether-CHCl3 graded solvent systems. The products were
crystallized from CHCl3-pet. ether (bp 40°- 60 °C).
= 7.2, 3.0 Hz). 13C-NMR , s), (CDCl3) δc 14.6, 18.9, 45.8, 57.2,
61.2, 109.5, 121.2, 133.5, 136.5, 146.9, 147.6, 148.0, 155.3,
155.7. MS: m/z (rel. int.) 295.0786, 293.0812 (M+) (Calc. for
C15H16ClNO3, 295.0789, 293.0819) (100), 267(52), 265(68),
252(57), 237(35), 223(42), 193(58), 179(56), 138(42), 112(44),
77(82). Anal. calcd. for C15H16ClNO3: C, 61.33; H, 5.49; N,
4.76.Found: C, 61.35; H, 5.51; N, 4.75.
5-Carboethoxy-6-methyl-4-phenyl-3,4-dihydro-pyridine-2-
one (4a). Colorless crystals, mp. 102-103°C. IR: νmax 3117, 2969,
1724, 1648, 1466, 1420, 1386, 1290, 1222, 1091, 1028, 782 cm-1.
1H-NMR(CDCl3, 200MHz): δ 1.16 (3H, t, J = 7.0 Hz), 2.17 (3H, s),
2.37 (2H, d, J = 3.4 Hz), 3.68 (1H, d, J = 3.4 Hz), 6.07 (1H, s br,
NH), 7.10-7.46 (5H, m). 13C-NMR (CDCl3): δc 13.7, 17.5, 43.5,
54.3, 59.9, 110.3, 120.8, 125.7, 127.9, 128.4, 139.5, 165.6, 171.3.
HRMS: m/z (rel. int.) 259.1216 (M +) (calcd. for C15H17NO3,
259.1209) (100), 231(30), 217(60), 203(36), 189(38), 159(55),
145(54), 104(26), 77(87). Anal. calcd. for C15H17NO3 : C, 69.48 ; H,
6.60 ; N, 5.40 .Found: C, 69.49 ; H, 6.62 ; N, 5.39.
5-Carboethoxy-6-methyl-4-(2-hydroxy)phenyl-3,4-dihydro-
pyridin-2-one (4f). Colorless crystals mp. 208-209°C. IR: νmax
3462, 3120, 2964, 2827, 1708, 1682, 1655, 1519, 1461, 1385,
1
1323, 1282, 1238, 1139, 1096, 1027, 866 cm-1. H-NMR (200
MHz, DMSO): δ 1.26 (3H, t, J = 7.1 HZ), 1.87 (3H, s), 2.37
(2H, s), 3.12 (2H, d, J = 3.4 Hz), 4.30 (2H, q, J = 7.1 Hz), 6.07
(1H, s br), 6.81 (2H, dd, J = 8.1, 2.3 Hz), 7.12 (1H, m), 7.22
(1H, dd, J = 8.1, 2.3 Hz). 13C-NMR δc 14.8, 18.5, 39.4, 55.3,
60.7, 110.9, 113.5, 128.3, 133.6, 136.3, 140.3, 146.5, 151.0,
153.9, 165.3. MS: m/z (rel. int.) 275.1149 (M +) (Calcd. for
C15H17NO4, 275.1158) 247(45), 233(62), 219(38), 205(37),
175(51), 151(53), 120(44), 93(76). Anal. calcd. For C15H17NO4:
C, 65.44; H, 6.22; N, 5.08. Found: C, 65.44 ; H, 6.20 ; N, 5.07.
5-(Carboethoxy)-4-(3,5-dichloro)phenyl-6-methyl-3,4-dihydro-
pyridin-2-one (4g). Colorless crystals, mp 189-190°C. IR: νmax
3100, 2965, 2830, 1700, 1682, 1658, 1510, 1467, 1385, 1323, 1282,
1236, 1140, 1096, 1030, 868cm-1. 1H-NMR (300 MHz, DMSO-d6):
δ 1.19 (3H, t, J = 7.1Hz), 2.23 (3H, s), 2.30 (2H, s), 4.01 (2H, q, J =
7.1 Hz), 4.23 (1H, d,J = 3.4 Hz), 5.19 (1H, s br), 7.42 (1H, d, J = 2.4
Hz), 7.76 (1H, dd, J = 8.2,2.4 Hz),8.12 (1H, d, J = 8.2 Hz). 13C-
NMR (DMSO-d6): δc 15.3, 18.6, 46.8, 55.0, 61.2, 108.3, 121.5,
133.6, 142.2, 147.5, 148.0, 148.6, 152.3, 156.7, 165.5. MS: m/z (rel.
int) 331.0458, 327.0440 (M +) (Cal. for C15H15NO3Cl2, 331.0450,
327.0431) (100), 301(36), 299(39), 286(61), 272(35), 258(34),
228(48), 214(51), 173(36), 147(74). Anal. calcd for: C15H15NO3Cl2:
C, 54.89; H, 4.60; N, 4.26. Found: C, 54.87; H, 4.59; N, 4.27.
5-Carboethoxy-4-(4-fluorophenyl)-6-methyl-3,4-dihydro-
pyridine-2-one (4h). Colorless crystals, mp 166-167°C. IR:
νmax 3000, 2968, 2845, 1698, 1660, 1515, 1475, 1380, 1326,
1292, 1236, 1145, 1090, 1030, 865cm-1. 1H-NMR (300 MH,
CDCl3): δ 1.21 (3H, t, J = 7.1 Hz), 2.50 (3H, s), 2.53 (2H, dd, J
= 3.4, 1.8 Hz), 4.13 (2H, q, J = 7.1 Hz), 5.17 (1H, d, J = 3.4 Hz),
5.60 (1H, s br), 7.12 (2H, dd, J = 8.6, 2.9 Hz), 7.62 (2H, dd, J =
8.6, 2.9 Hz). 13C-NMR (CDCl3): δc 14.9, 18.6, 50.8, 53.1, 61.2,
98.9, 115.1, 128.1, 128.2, 140.9, 146.5, 159.9, 166.5, 165.8. MS:
m/z (rel. int.) 277.1125 (M+) (Calcd. for C15H16FNO3, 277.1114)
(100), 249(32), 221(66), 207(32), 177(67), 163(55), 122(63),
96(65), 77(72). Anal. calcd. for C15H16FNO3: C, 64.97; H, 5.81;
N, 5.05. Found: C, 64.96; H, 5.80; N, 5.07.
5-Carboethoxy-6-methyl-4-(4-methoxy)phenyl-3,4-dihydro-
pyridin-2-one (4b). Colorless crystals, mp 137-138°C. IR: νmax
2995, 2874, 2265, 1685, 1578, 1510, 1445, 1410, 1340, 1305,
1285, 1040 1017, 866 cm-1. 1H-NMR (300 MHz, CDCl3): δ 1.09
(3H, t, J = 7.1 Hz), 1.87 (1H, s), 2.22 (3H, s), 2.40 (2H, dd, J =
1.4, 3.7 Hz), 3.75 (3H, s), 3.93 m (1H, d, J = 3.7, 1.7 Hz), 3.98
(2H, q, J = 7.1 Hz), 6.80 (2H, d, J = 8.7 Hz), 7.16 (2H, d, J = 8.7
Hz). 13C-NMR (CDCl3): δc 18.6, 24.1, 40.6, 55.3, 60.0, 101.5,
109.5, 109.7, 118.6, 136.3, 148.3, 153.3, 165.7. MS : m/z (rel.
int.) 289.1323 (M+) (calcd. for C16H19NO4, 289.1315) (100),
274(34), 261(47), 247(59), 233(33), 189(52), 175(50), 134(42),
107(69), 92(49). Anal. calcd. for C16H19NO4: C, 66.42 ; H, 6.61;
N, 4.84. Found: C, 66.41; H, 6.62; N, 4.83.
5-Carboethoxy-6-methyl-4(4-chloro)phenyl-3,4-dihydro-
pyridin-2-one (4c). Colorless crystals, mp. 178-179°C. IR: νmax
3001, 2875, 2776, 2250, 1695, 1628, 1570, 1530, 1510, 1445,
1366, 1340, 1290, 1060, 1017, 960 cm-1. 1H-NMR (300
MHz,CDCl3): δ 1.19 (3H, t, J = 7.1 Hz), 2.13 (3H, s), 2.39 (2H,
d, J = 3.1 Hz), 4.07 (1H, d, J = 3.1 Hz), 4.20 (2H, q, J = 7.1 Hz),
5.80 (1H, s br), 7.44 (2H, d, J = 8.4 Hz), 7.75 (2H, d, J = 8.4
Hz). 13C NMR (CDCl3): δc 14.5, 19.6, 43.2, 53.1, 60.0, 101.1,
121.2, 127.6, 133.5, 137.3, 148.0, 148.7, 154.5, 154.6, 165.3.
MS: m/z (rel. int.) 293.0892, 295.0798 (M+) (Calc. for
C15H16ClNO3, 293.0819, 295.0789), 275(36), 273(28), 265(39),
253(36), 251(68), 223(46), 237(67), 179(55), 138(16), 112(72),
77(48). Anal. calcd. for C15H16ClNO3: C, 61.33 ; H, 5.49 ; N,
4.76. Found: C, 66.41; H, 5.52; N, 4.78.
5-Carboethoxy-6-methyl-4(3,4-dimethoxy)phenyl-3,4-dihydro-
pyridin-2-one (4d). Colorless crystals, mp 112-113°C. IR: νmax
3174, 2973, 2603, 2265, 1699, 1605, 1578,1515, 1445, 1340, 1305,
1
1278, 1210, 1160, 1017, 984cm-1. H-NMR (CDCl3, 300 MHz): δ
1.20 (3H, t, J = 7.2 Hz), 2.34 (3H, s), 2.58 (2H, d, J = 3.7 Hz), 3.62
(3H, s), 3.67 (3H, s), 3.85 (1H, d, J = 3.7 Hz), 4.07 (2H, q, J = 7.1
Hz), 5.90 (1H, s br), 6.67 (1H, d, J = 3.1 Hz), 6.89 (1H, d, J = 8.6
Hz), 7.12 (1H, d, J = 8.6 Hz). 13C-NMR (CDCl3): δc 14.1, 18.6,
20.6, 40.3, 55.3, 55.8, 60.0, 101.5, 109.8, 111.0, 118.6, 136.3,
148.6, 148.9, 153.4, 165.7. MS: m/z (rel. int) 319.1432 (M+) (Calc.
for C17H21NO5 319.1420), 281(23), 277(63), 263(42), 249(38),
219(55), 205(62), 164(59), 77(76). Anal. calcd. for C17H21NO5: C,
63.93; H, 6.62 ;N, 4.38. Found: C, 63.95; H, 6.64; N, 4.39.
5-Carboethoxy-6-methyl-4(2-hydroxy-4-methoxy)phenyl-
3,4-dihydropyridin-2-one (4i). Colourless solid mp 215-216
°C. IR νmax 3500, 3047, 3005, 2846, 1656, 1600, 1578, 1511,
1445, 1340, 1305, 1263, 1212, 1170, 1017, 984 cm-1. 1H-NMR
(300 MHz,DMSO-d6): δ 1.02 (3H, t, J = 7.1 Hz), 2.0 (3H, s),
2.46 (2H, d, J = 3.2 Hz), 3.83 (3H, s), 3.92 (5H, q, d, J = 7.1, 3.2
Hz), 6.60 (1H, d, J = 3.2 Hz), 6.68 (1H, d, J = 8.0 Hz), 6.84 (1H,
d, J = 8.0 Hz), 8.70 (1H, s br), 9.12 (1H, s, br). 13C-NMR
(DMSO-d6): δc 14.8, 18.5, 44.8, 55.8, 56.4, 60.6, 99.2, 109.6,
112.3, 119.2, 144.01, 148.5, 149.6, 153.7, 156.5, 166.8 MS : m/z
(rel. int.) 305.1253 (M+) (Calcd. for C16H19NO5, 305.1265),
277(28), 263(44), 261(58), 235(49), 233(52), 205(61), 191(52),
124(82), 110(61).Anal. calcd. for C16H19NO5: C, 62.94; H, 6.27;
N, 4.58. Found: C, 62.95; H, 6.28; N, 4.57.
5-Carboethoxy-6-methyl-4-(2-chloro)phenyl-3,4-dihydro-
pyridin-2-one (4e). Colorless crystal, mp 154-155°C. IR: νmax
3244, 3117, 2969, 1700, 1648, 1599, 1466, 1420, 1386, 1313,
1
1290, 1222, 1091, 1028, 782. H-NMR (CDCl3, 200MHz): δ
1.05 (3H, t, J = 6 Hz), 2.42 (3H, s), 2.74 (2H, d, J = 3.2 Hz),
3.97 (1H, d, J = 3.2 Hz), 3.99 (2H, q, J = 6.6 Hz), 5.72 (1H, s
br), 7.21 (1H, dd, J = 7.2, 3.0 Hz), 7.35 (2H, m), 7.39 (1H, dd, J
5-Carboethoxy-6-ethyl-4-(3,4-dioxymethylene)-phenyl-3,4-
dihydropyridin-2-one (4j). Colorless crystals mp 137-138 °C.

Mar-Apr 2008 Simpleand EfficientOne-potSynthesisof 3,4-Dihydro-2-pyridonesviaSolid-Supported Bi(III)nitrate
355
Table 3
IR: νmax 3060, 3004, 2837, 1659, 1598, 1572, 1446, 1422, 1336,
1
1293, 1256, 1172, 1113, 1071, 1035, 1018, 828, 778 cm-1. H-
Crystal data and structure refinement for 4e
NMR (CDCl3, 200 MHz): δ 1.19 (3H, t, J = 7.1 Hz), 2.34 (3H,
s), 2.55 (2H, d, J = 3.7 Hz), 3.85 (1H, d, J = 3.7 Hz), 4.07 (2H,
q, J = 7.1 Hz), 6.80 (1H, s), 6.84 (1H, d, J = 8.6 Hz), 7.18 (1H,
dd, J = 8.6, 2.3 Hz). 13C NMR (CDCl3): δc 16.5, 19.8, 51.2,
53.4, 60.2, 101.1, 102.5, 112.5, 114.8, 118.6, 137.6, 149.9,
149.1, 154.2, 165.3. MS: m/z (rel. int.) 303.1101 (M+) (Calcd. for
C16H17NO5, 303.1107), 275(49), 273(59), 230(66), 216(45),
211(35), 183(64), 175(56), 142(32). Anal. calcd. for C16H17NO5 :
C, 63.35 ; H, 5.64 ; N, 4.61. Found: C, 63.34; H, 5.65; N, 4.60.
5-Carboethoxy-6-methyl-4-(4-cyano)phenyl-3,4-dihydro-
pyridin-2-one (4k). Colorless crystals mp 168-169°C. IR: νmax
3032, 3005, 2859, 1676, 1650, 1600, 1578, 1573, 1515 1490,
Identification code
Empirical formula
Formula weight
Temperature
Wavelength
4e
C15H16ClNO3
293.74
293(2) K
0.71069 A
TRICLINIC, P-1
a = 7.685(5) A alpha = 92.800(5) deg.
b = 8.232(5) A beta = 100.190(5) deg.
C = 11.846(5) A gamma = 108.560(5) deg.
694.8(7) A^3
Crystal system, space group
Unit cell dimensions
Volume
Z, Calculated density
Absorption coefficient
F(000)
Crystal size
Theta range for data collection 1.76 to 25.50 deg.
Limiting indices
Reflections collected / unique 2706/2497 [R (int) = 0.0251]
Completeness to theta = 25.50 96.4%
Absorption correction
Refinement method
Data / restraints / parameters
Goodness-of-fit on F^2
Final R indices [I>2sigma(I)] R1 = 0.0612, wR2 = 0.1818
R indices (all data)
Largest diff. peak and hole
2, 1.404 Mg/m^3
0.281 mm^-1
308
1
1447, 1340, 1305, 1260, 1212, 1170, 1017, 984 cm-1. H-NMR
0.02x0.02x0.03 mm
(200 MHz,CDCl3) δ 1.12 (3H, t, J = 7.1 Hz), 2.29 (3H, s), 2.66
(2H, d, J = 3.2 Hz), 4.00 (2H, q, J = 7.1 Hz), 4.16 (1H, d, J = 3.5
Hz), 7.63 (2H, dd, J = 8.1 Hz), 7.83 (2H, dd, J = 8.1 Hz), 5.63
(1H, s br). 13C-NMR (CDCl3) : δc 12.4, 16.3, 40.4, 56.4, 59.5
0<=h<=8, -9<=k<=9, -14<=1<=14
None
108.0, 125.8, 130.5, 147.6, 148.3, 153.5, 163.5. MS: m/z (rel.
Full-matrix least-square on F^2
2497 / 0 / 181
0.978
+
.
int) 284.1172 (M ) (Cal. For C16H16N2O3 284.1161), 256(20),
242(58), 228(42) 214(47), 170(58), 129(35), 103(68), 77(81).
Anal. calcd. for :C16H16N2O3: C, 67.59; H, 5.67; N, 9.85. Found :
C, 67.58; H, 5.66; N, 9.84.
R1 = 0.1054, wR2 = 0.2089
0.420 and -0.578 e.A^-3
3-Carboethoxy-4-furfryl-6-methyl-3,4-dihydropyridin-2-
one (4 l). Colorless crystals mp 110-111°C. IR: νmax 3227, 3110,
2973, 1698, 1645, 1499, 1454, 1381, 1300, 1292, 1151, 1100,
1014, 927, 799cm-1. 1H-NMR (300 MHz,CDCl3) δ 1.21 (3H, t, J
= 7.1 Hz), 2.32 (3H, s), 2.82 (2H, d, J = 3.1 Hz), 4.13 (2H, q, J =
7.1 Hz), 5.44 (1H, d, J = 3.1 Hz), 5.63 (1H, s br), 6.10 (1H, d, J
= 1.9 Hz), 6.27 (1H, dd, J = 0.9, 1.7 Hz), 7.32 (1H, dd, J = 1.7
Hz). 13C-NMR (CDCl3) δc 15.6, 19.4, 42.5, 60.8, 63.2, 99.6,
107.3, 130.5, 131.1, 133.4, 143.4, 153.1, 166.7. MS: m/z (rel.
int.) 249.1012 (M+) (Calc. for C13H15NO4, 249.1001), 221(46),
207(58), 193(47), 179(56), 149(68), 135(44), 94(33), 67(78).
Anal. calcd. for; C13H15NO4: C, 62.64; H, 6.06; N, 5.61. Found:
C, 62.62; H, 6.04; N, 5.59.
5-Carboethoxy-4(4-nitro)phenyl-6-methyl-3,4-dihydropyri-
din-2-one(4m). Pale yellow crystals mp 132-133°C. IR: νmax 3010,
2876, 2825, 1690, 1672, 1656, 1530, 1460, 1385, 1325, 1285,
1238, 1140, 1090, 1025, 870 cm-1. 1H-NMR (300 MHz, CDCl3) δ
1.16 (3H, t, J = 7.1 Hz), 2.23 (3H, s), 2.51 (2H, dd, J = 3.6, 1.8
Hz), 3.32 (1H, d, J = 3.6 Hz), 4.01 (2H, q, J = 7.1 Hz), 7.51 (2H,
d, J = 8.7 Hz), 8.20 (2H, d, J = 8.7 Hz). 13C-NMR (CDCl3) δc
18.6, 19.1, 53.6, 53.7, 60.1, 109.4, 123.8, 127.9, 146.6, 148.9,
151.6, 153.2, 163.9. MS: m/z (rel. int.) 303.0969 (M+) (Calc. for
C15H15N2O5, 303.0981), 275(46), 257(53), 247(58), 261(58),
233(37), 189(49), 148(56), 77(71). Anal. calcd .for :C15H15N2O5:
C, 59.20 H, 5.30 N, 9.20. Found: C, 59.22; H, 5.26; N, 9.21.
Table 4
Atomic coordinates (x104) and equivalent isotropic displacement parameters (Å2 x 103) for 4e. U (eq) is defined as one third of the trace of the
orthogonalized Uij tensor.
x
y
z
u(eq)
C (1)
C (2)
C (3)
C (4)
C (5)
C (6)
C (7)
C (8)
C (9)
C (10)
C (11)
C (12)
C (13)
C (14)
C (15)
N (1)
O (2)
O (3)
O (1)
Cl
4455 (5)
3983 (4)
2135 (5)
651 (5)
2457 (5)
802 (4)
-334 (5)
435 (5)
2083 (5)
3045 (5)
-686 (5)
-3471 (7)
-4853 (8)
-595 (5)
801 (6)
9303 (3)
8902 (3)
8283 (3)
8519 (3)
8940 (3)
9154 (4)
8266 (3)
7512 (5)
6763 (6)
7011 (3)
6358 (4)
5214 (4)
4673 (5)
5287 (5)
6429 (4)
9231 (4)
8406 (3)
7835 (3)
9741 (3)
7139 (1)
44 (1)
27 (1)
39 (1)
38 (1)
41 (1)
57 (1)
47 (1)
95 (2)
114 (2)
42 (1)
60 (1)
86 (2)
95 (2)
80 (2)
56 (1)
48 (1)
67 (1)
66 (1)
63 (1)
82 (1)
1133 (5)
-161 (5)
-1314 (5)
-3419 (7)
-3509 (9)
2126 (5)
2338 (6)
2435 (8)
2312 (8)
2076 (7)
1985 (5)
2997 (4)
-2661 (4)
-1503 (4)
6055 (4)
1723 (2)
651 (9)
-917 (10)
-2321 (8)
-2163 (5)
3102 (4)
-297 (4)
-2272 (4)
3376 (4)
-3986 (2)

356
J. Singh, S. Koul, A. P. S. Pannu, R. L. Sharma and T. K. Razdan
Vol 45
Table 5
Bond lengths [A] and angles [deg.] for 4e.
C (1) -O (1)
C (1) -C (2)
C (1) -N (1)
C (2) -C (3)
C (3) -C (10)
C (3) -C (4)
C (4) -C (5)
C (4) -C (7)
C (5) -N (1)
C (5) –C (6)
C (7) –O (2)
C (7) –O (3)
C (8) –C (9)
C (8) –O (3)
C (10) –C (15)
C (10) –C (11)
C (11) –C (12)
C (12) –C (13)
C (13) –C (14)
C (14) –C (15)
C (15) –Cl
1.224 (4)
1.332 (5)
1.376 (5)
1.466 (4)
1.510 (5)
1.528 (5)
1.333 (5)
1.468 (5)
1.381 (5)
1.500 (5)
1.212 (4)
1.332 (5)
1.384 (7)
1.458 (5)
1.396 (5)
1.400 (6)
1.372 (6)
1.381 (8)
1.375 (8)
1.369 (7)
1.729 (5)
O (1) –C (1) –C (2)
O (1) –C (1) –N (1)
C (2) –C (1) –N (1)
C (1) –C (2) –C (3)
C (2) –C (3) –C (10)
C (2) –C (3) –C (4)
C (10) –C (3) –C (4)
C (5) –C (4) –C (7)
C (5) –C (4) –C (3)
C (7) –C (4) –C (3)
C (4) –C (5) –N (1)
C (4) –C (5) –C (6)
N (1) –C (5) –C (6)
O (2) –C (7) –O (3)
O (2) –C (7) –C (4)
O (3) –C (7) –C (4)
C (9) –C (8) –O (3)
C (15) –C (10) –C (11)
C (15) –C (10) –C (3)
C (11) –C (10) –C (3)
C (12) –C (11) –C (10)
C (11) –C (12) –C (13)
C (14) –C (13) –C (12)
C (15) –C (14) –C (13)
C (14) –C (15) –C (10)
C (14) –C (15) – Cl
C (10) –C (15) – Cl
C (1) –N (1) –C (5)
C (7) –O (3) –C (8)
124.1 (3)
120.2 (3)
115.7 (3)
127.1 (3)
110. 1 (3)
109.0 (3)
112. 4 (3)
121.0 (3)
120.8 (3)
118.3 (3)
120.4 (3)
127.0 (3)
112.6 (3)
121.3 (4)
127.1 (4)
111.7 (3)
110.6 (4)
116.3 (4)
123.8 (4)
119.8 (3)
122.0 (5)
119.9 (5)
119.5 (5)
120.4 (5)
121.9 (5)
117.3 (4)
120.9 (3)
123.4 (3)
115.9 (3)
Symmetry transformation used to generate equivalent atoms:
Table 6
REFERENCES
Anisotropic displacement parameters (A2 x 103) for 4e.
[1] (a) Schultz, A. Chem. Rev 1973, 73, 385. (b) Emtenas, H.;
Alderin, L.; Almqvist, F. J. Org. Chem. 2001, 66, 6756. (c) Stilli, J. R.;
Barta, N. S. Studies in Natural Product Chemistry Elsevier Science,
Amsterdam, 1966; vol. 18, pp 315 (d) Bradley, J. C.; Buchi, G., J. Org.
Chem. 1976, 41, 699.
The anisotropic displacement factor exponent takes the form:
2π2[h2a*2U11+ ……. +2h k a* b* U12]
-
U12
U11
U22
U33
U23
U13
[2] Kelly, T.; Bell, S.; Osashi, N.; Amtrong-Chong, J. J. Am.
Chem. Soc. 1988, 110, 6471.
[3] (a) Cox, R.; O’ Hagan, D. J. Chem. Soc., Perkin Trans. I,
1991, 2537. (b) Mynderse, J. S.; Samlaska, S. K.; Fukuda, D. S.; DuBus,
R. H.; Baker, P. J. J. Antibiot. 1985, 38, 1003.
[4] (a) O’ Connor, S.; Somers, P. J. Antibiot. 1985, 38, 993. (b)
Hunt, A. H.; Mynderse, J. S.; Samlaska, S. K.; Fukuda, D.; Maciak, G.
M.; Kirst, H. A.; Occolowitz, J. L.; Swartzen-druber, J. K.; Jones, N. D.
J. Antibiot. 1988, 41, 771.
[5] (a) Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H.;
McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1966, 88, 3888. (b)Aberg,
V.; Hedenstrom, M.; Pinkner, J. S.; Hultgren, S. J.; Almqvist, F. Org.
Biomal. Chem. 2005, 3, 3886.
[6] (a) Comins, D. L.; Nolan, J. M. Org. Lett. 2001, 3, 4255. (b)
Potmesil,, M. Cancer Res., 1994, 54, 1431. (c) Rice-Evans, C. A.;
Burdon, R. H., Free Radical Damage and its Control; Elsevier,
Amsterdam, 1994.
[7] (a) Josien, H.; Curran, D. P. Tetrahedron 1997, 53, 8881. (b)
Williams, D.; Lowder, P.; Gu, Y. G. Tetrahedron Lett. 1997, 38, 327.
[8] Kozkowski, A.; Campiani, G.; Sun, L. Q.; Wang, S.; saxena,
A.; Doctor, B. J. Am. Chem. Soc. 1996, 118, 11357.
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10) 27 (2)
C(11) 57 (3)
C(12) 79 (4)
C(13) 83 (4)
C(14) 70 (3)
C(15) 38 (2)
N(1) 32 (2)
O(2) 32 (2)
O(3) 36 (2)
O(1) 29 (2)
27 (2)
19 (2)
30 (2)
29 (2)
29 (2)
39 (2)
34 (2)
52 (3)
83 (4)
54 (2)
34 (2)
39 (2)
45 (2)
48 (2)
56 (2)
57 (2)
83 (14)
91 (4)
48 (2)
69 (3)
120 (5)
157 (6)
105 (4)
61 (3)
42 (2)
74 (2)
52 (2)
61 (2)
52(1)
51 (2)
30 (2)
47 (2)
41 (2)
47 (2)
81 (3)
45 (2)
120 (5)
129 (5)
49 (2)
53 (3)
63 (3)
49 (3)
67 (3)
65 (3)
68 (2)
96 (2)
97 (2)
91 (2)
120 (1)
-8 (2)
-4 (1)
-2 (2)
-2 (2)
-1 (2)
-5 (2)
-3 (2)
-34 (2)
-35 (4)
-6 (2)
3 (2)
26 (3)
-10 (4)
-32 (3)
-19 (2)
-15 (2)
-5 (2)
-21 (2)
-28 (2)
-12 (1)
6 (2)
2 (1)
9 (2)
7 (2)
8 (2)
16 (2)
10 (2)
38 (3)
20 (4)
8 (2)
17 (2)
26 (3)
13 (3)
5 (3)
7 (2)
7 (2)
18 (2)
21 (2)
3 (1)
Cl
75 (1)
23 (1)
[9] (a) Aggarwal, V.; Singh, G.; Illa,H.; Jungrappa, H. Synthesis
1982, 214. (b) Datta, A.; Illa,H.; Junjappa, H. J. Org. Chem. 1990, 55, 5589.
(c) Chuit, C.; Corriu, R. J. P.; Perz, R.; Reye, C. Tetrahedron 1986, 42,
2293. (d) Padwa, A.; Heidelbaugh, T. M.; Kuethe, J. T. J. Org. Chem. 2000,
65, 2368. (e) Gurski-Birchler, A.; Liu, F.; Liebeskind, L. S. J. Org. Chem.
Acknowledgement. The author are thankful to Prof. Hundal
G. N. D. University Amritsar for X-ray analysis, Dr. Simon
Fraser (University, British Columbia, Canada) and Mrs. B. P.
Wakhlu (R.R.L Jammu) spectral analysis.

Mar-Apr 2008 Simpleand EfficientOne-potSynthesisof 3,4-Dihydro-2-pyridonesviaSolid-Supported Bi(III)nitrate
357
1994, 59, 7737. (f) Tomas, M.; Suarez-Sobrino, A.; Gotor, V. Tetrahedron
Lett. 1988, 29, 4855. (g) Takaoka, K.; Aoyama, T.; Shioiri, T. Tetrahedron
Lett. 1996, 37, 4973. (h) Katrizky, A.; Belyakov, S.; Sorochinsky, A.;
Henderson, A.; Chen, J. J. Org. Chem. 1997, 62, 6210. (i) Grosche, P.;
Holtzel, A.; Walk, T. B., Trautwein, A. W.; Jung, G. Synthesis, 1999, 1961.
(j) Linn, J. A.; Gerritz, S. W.; Handlon, A. L.; Hyman, C. E.; Heyer, D.
Tetrahedron Lett. 1999, 40, 2227. (k) Brun, E.; Gil, S. Mesters,R.; Parra,
M., Synthesis 2000, 273. (l) Paulvannan, K.; Chen, T., J. Org. Chem. 2000,
65, 6160. (m) Wagman, A. S.; Wnag, L.; Nuss, J. M. J. Org. Chem. 2000,
65, 9103. (n) Emtenas, H.; Ahlin, K.; Pinkner, J. S.; Hultgren, S. J.;
Almqvist, F. J. Comb. Chem. 2002, 4, 630. (o) Cherry, K.; Abarbri, M.;
Parrian J. L.; Duehene, A. Tettrahedron. Lett., 2003, 44, 5791.
[10] Mohrle, H.; Neber,W. Tetrahedron, 1970, 26, 2953. (b)
McKillop, A.; Boulton, A. Comprehensive Heterocyclic Chemistry,
Pergamon Oxford, 1984, vol., 2, p 67.
[11] Hung, D. L.; Knight, S. D.; Woods,R. M.; Pinkner, J. S.;
Hultgren, S. J. EMBOJ, 1996, 15, 3792.
[12] Jones, G. Org. React, 1967, 15, 204.
[13] Kumar, A., Koul, S., Razdan, T. K.; Kapoor, K. K.
Tetrahedron Lett., 2006, 47, 837.
[14] Mukhopadhyay, C.; Becker, F. F. and banik, B. K. J. Chem.
Res. Synop. 2001, 28 and refs. 10 and 11 therein and footnote 16.