A novel application of the oxidizing properties of urea nitrate and peroxydisulfate-cobalt(II): Aromatization of NAD(P)H model Hantzsch 1,4-dihydropyridines

Article abstract of DOI:10.1016/S0040-4020(02)00461-1

4-Alkyl or aryl substituted derivatives of Hantzsch 1,4-dihydropyridine were readily oxidized by urea nitrate under microwave irradiation or refluxing conditions to the corresponding pyridine derivatives in quantitative yields. The oxidation reaction was

Full text of DOI:10.1016/S0040-4020(02)00461-1

TETRAHEDRON
Pergamon
Tetrahedron 58 .2002) 5069±5073
A novel application of the oxidizing properties of urea nitrate and
peroxydisulfate-cobaltꢀII): aromatization of NADꢀP)Hmodel
Hantzsch 1,4-dihydropyridines
Marimuthu Anniyappan, D. Muralidharan and Paramasivan T. Perumalp
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
Received 19 February 2002; revised 27March 2002; accepted 1 May 2002
AbstractÐ4-Alkyl or aryl substituted derivatives of Hantzsch 1,4-dihydropyridine were readily oxidized by urea nitrate under microwave
irradiation or re¯uxing conditions to the corresponding pyridine derivatives in quantitative yields. The oxidation reaction was also effected
by peroxydisulfate in the presence of cobalt.II) in aqueous acetonitrile under re¯uxing conditions. When n-propyl, n-butyl and cinnamyl
were the substituent groups in the 4-position, a mixture of 4-substituted and unsubstituted pyridines were formed. The catalysts used in the
reaction are inexpensive and provide high yields in short reaction times. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
According to Maquestiau et al.,5 Claycop is not an ef®cient
reagent for the aromatization of Hantzsch 1,4-dihydro-
pyridines bearing an alkyl group in the 4-position even
under sonication conditions.
Hantzsch 1,4-dihydropyridine derivatives which contain the
1,4-dihydropyridine structure of the natural reduced nico-
tinamide adenine dinucleotide [NAD.P)H] coenzyme play a
vital role in many bioreductions by transferring a hydride
ion or an electron to the surrounding substrate1 and possess a
high biological activity as a class of useful drugs, particu-
larly as antioxidants. The 4-substituted-2,6-dimethyl-3,5-
pyridine dicarboxylic acid diethyl esters have anti-hypoxic
and anti-ischemic activities. Some of the representatives of
this class have acaricidal, insecticidal, bactericidal and
herbicidal activities.2
However most of these reactions require an extended period
of time for completion, utilize strong oxidants in large
excess and afford only modest yields of the products. In
recent times, much attention has been paid to the use of
microwave irradiation in organic synthesis due to added
advantages like substantial reduction in reaction time and
higher heating ef®ciency.11 Result and discussion in this
paper, we report the development of a novel, simple and
milder method for the oxidation of Hantzsch 1,4-dihydro-
pyridines to the corresponding pyridine derivatives using
urea nitrate in acetonitrile under both microwave irradiation
and re¯uxing conditions with high yield in short reaction
times .Scheme 1). Urea nitrate has been used for regio-
selective nitration of 4-halonitrobenzene to 4-halo-ortho-
dinitro benzene12a and aromatic amines.12b Recently we
reported the utility of urea nitrate as an ef®cient catalyst
for the imino Diels±Alder reactions.13 The suspension of
The oxidation of Hantzsch 1,4-dihydropyridines is one of
the ubiquitous issues in organic chemistry and even in
recent years several groups have reported various new
methods for aromatization including oxidation with ferric
nitrate on a solid support,3 ceric ammonium nitrate,4 clay-
supported cupric nitrate .Claycop),5 pyridinium chloro-
chromate,6 bromo trichloromethane,7 nitric acid,8 nitric
oxide and N-methyl-N-nitrosotoluene-p-sulfonamide.9,10
Scheme 1.
Keywords: 1,4-dihydropyridines; urea nitrate; peroxydisulphate-cobalt.II); oxidation; pyridine derivatives.
Corresponding author. Tel.: 191-44-4913289; fax: 191-44-4911589; e-mail: ptperumal@hotmail.com
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020.02)00461-1

5070
M. Anniyappan et al. / Tetrahedron 58 '2002) 5069±5073
Scheme 2.
urea nitrate in solvent slowly releases nitric acid, which is
involved in the oxidation reaction. Since urea nitrate is
inexpensive and easy to prepare,14 we explored its ability
to catalyze the oxidation reaction effectively in shorter
reaction times.
which gave 4-methyl pyridine .16). The products were
analyzed by GC-MS.
Investigations on the oxidation ef®ciency of peroxydisulfate
alone at ambient temperature as well as higher temperature
indicated that in the absence of metal ion, oxidation of 1,4-
dihydropyridines into aromatized products by the sulfate
radical anion is less effective.23 In conclusion we opine
that the peroxydisulfate-cobalt.II) nitrate reagent offers a
rate enhancement, due to the presence of cobalt.II) which
increases the rate of decomposition of peroxydisulfate to
form a sulfate radial anion and a cobalt.III) ion, the
cobalt.III) ion initiates the oxidation reaction by abstracting
an electron on the nitrogen of 1,4-dihydropyridine to give
Co.II) ions.24
Peroxydisulfate ion is one of the versatile oxidizing agents
in aqueous solution,15 employed in many organic reactions
in the presence of metal acetates,16 cobalt.III) acetate17 and
copper ion.18 The reactions involving this ion are generally
slow at ambient temperature and the rate of peroxydisulfate
decomposition increases by many folds when the tempera-
ture is raised.15 The standard oxidation±reduction potential
of the reaction is estimated to be 2.01 V.15
The oxidation of 4-alkyl or aryl substituted dihydro-
pyridines with potassium peroxydisulfate in the presence
of cobalt.II) in aqueous acetonitrile by re¯uxing on a
water bath to the corresponding pyridine derivatives
proceeded in high yields .Scheme 2) The results obtained
with various 4-substituted 1,4-dihydropyridines are given in
Table 1.
The possible mechanism of the oxidation reaction using
peroxydisulfate in presence of cobalt.II) which involves
an initial one electron transfer from 1,4-dihydropyridine
.I) to the cobalt.III) ion to give radical cation II. This radical
cation loses a proton to form an intermediate III, which
transfers an electron to the sulfate radical anion or Co.III)
to form the cation IV, subsequently results in the aromatized
product.s) V by homolysis .Scheme 3).
According to earlier studies, oxidation of 4-alkyl dihydro-
pyridines containing methyl, ethyl, propyl and cinnamyl
substituents produced exclusively 4-alkyl pyridine
.A).10,19±21 Contrary to this, we observed during our studies
that 4-alkyl substituted dihydropyridines .3, 4 and 13)
resulted in a mixture of 4-substituted and unsubstituted pyri-
dines .A and B). This is in agreement with the observation
of Delgado et al.22 except for 4-methyl dihydropyridine,
The in¯uence of the various solvents on the yield of the
reaction was investigated using compound 1 as the
substrate. The results obtained show that acetonitrile is a
better choice for the oxidation reaction. This can be
attributed to the enhanced solubilizing power of the solvent
for the oxidant as well as the substrate .Table 2).
Table 1. Oxidation of Hantzsch 1,4-dihydropyridine with urea nitrate and peroxydisulfate-cobalt.II)
Compound
R
Product.s)a
Peroxydisulphate-Co.II)b
Yields .%)d
Urea nitratec
Re¯uxing conditions Microwave irradiation
Time .min)
A
B
Time .h)
Yield .%)d
Time .min)
Yield .%)d
1
2
3
4
5
6
7
8
H
CH3
n-C3H7
n-C4H9
C6H5
15
16
17
18
19
20
21
22
23
24
25
26
27
28
10
10
10
15
10
15
15
15
15
10
15
15
10
10
±
96
±
1.5
2
2
2
2
2.5
3
2
92 .B)
94
90
92
91
89
86
84
82
85
80
85
88
0.5
1
1
1
1.5
2
2
2
1
2
98 .B)
97
92
95
98
94
95
91
90
92
89
94
92
95
78
76
96
94
92
94
92
95
93
89
18
94
15e
20e
m-NO2C6H4
p-NO2C6H4
p-CH3C6H4
p-CH3OC6H4
2-Thienyl
2-Furyl
N-Benzenesul-fonyl-3-Indolyl
PhCHvCH
CH3CHvCH
9
2
10
11
12
13
14
2.5
2.5
3
3
3
2
2
2
2
72e
±
84
91
a
All the products were characterized by IR, NMR and GC-MS.
b
c
d
e
The reaction was carried out with equimolar amount of peroxydisulfate and cobalt.II) nitrate in aqueous CH3CN under re¯uxing conditions.
The reaction was carried out with 20 mol% urea nitrate under microwave irradiation.
The yield is based on isolation by column chromatography.
The yield ratio is based on GC analysis.

M. Anniyappan et al. / Tetrahedron 58 '2002) 5069±5073
5071
Scheme 3.
ethyl acetoacetate under microwave irradiation as reported
by us earlier.11e Potassium peroxydisulfate and cobalt .II)
nitrate were obtained from E-Merck India Ltd. Reagent
grade acetonitrile and other solvents were used. The percent
conversion was determined by GC-MS using a Perkin±
Elmer Auto System XL Gas Chromatography with Turbo
Mass spectrometer .EI, 70 eV), with helium as carrier gas at
a ¯ow rate of 1.0 mL/min, Perkin Elmer Elite series PE-5,
Table 2. Effect of the solvent medium on the reaction yield of 1 with urea
nitrate and peroxydisulfate-Co.II)
Entry
Solvent
Peroxydisulphate-Co.II)a
yield .%)b
Urea nitrate
.20 mol%)c
yield .%)b
1
2
3
4
5
6
CHCl3
MeOH
CH2Cl2
THF
CH3CN
Benzene
15
72
30
45
96
25
45
65
25
70
98
38
capillary
column
.30 m£0.25 mm£1 mm),
oven
programmed between 100 and 2608C at the rate of 108C/
min. Melting points were determined in capillary tubes and
are uncorrected. Analytical TLC was performed on
precoated plastic sheets of silica gel G/UV-254 of 0.2 mm
thickness .Macherey-Nagel, Germany). Fractionation of the
products was performed by column chromatography with
silica gel .60±120 mesh; s.d Fine chem Ltd. India). IR
spectra were recorded as neat .for liquids) and as KBr
pellets for solids on a Perkin Elmer Spectrum RXI FT-IR.
1H NMR spectra were recorded on a Bruker instrument at
300 MHz in CDCl3 and the chemical shifts are given in d
relative to the internal standard TMS. 13C NMR spectra
were recorded at 75 MHz in CDCl3 and the chemical shifts
are given in d relative to the solvent .77.0).
a
The reaction was carried out with equimolar amount of peroxydisulfate
and cobalt .II) nitrate under re¯ux for 10 min.
The yield is based on isolation by column chromatography.
The reaction was carried out with 20 mol% urea nitrate under microwave
irradiation for 30 s.
b
c
2. Conclusion
In summary, the present work offers a simple oxidation
method, employing readily available reagents and avoiding
dry and inert atmospheric conditions employed previously,
leading to better yield of pyridines from dihydropyridines.
Of the two systems under investigation urea nitrate was
found to yield only one product in contrast to peroxy-
disulfate-cobalt.II). In addition the catalysts employed in
this reaction are cost effective and provide quantitative
yield in short reaction times.
3.1. Oxidation of Hantzsch 1,4-dihydropyridines with
urea nitrate ꢀ20 mol%): general procedure
.i) To a solution of 1,4-dihydropyridine .2 mmol) in 20 mL
of acetonitrile, urea nitrate .0.0735 g, 20 mol%) was added.
The resulting mixture was re¯uxed on a water bath for the
appropriate time. .ii) Identical quantities of the substrate,
reagent and solvent were taken in a 250 mL of open conical
¯ask and subjected to microwave irradiation. After ascer-
taining the completion of the reaction by TLC, the reaction
mixture was extracted with CH2Cl2 .30 mL£2). The
combined organic layer was dried using anhydrous
3. Experimental
4-Substituted Hantzsch 1,4-dihydropyridines were prepared
using the appropriate aldehyde, ammonium acetate and

5072
M. Anniyappan et al. / Tetrahedron 58 '2002) 5069±5073
Na2SO4 and the solvent was distilled. The product was puri-
®ed by short silica gel column using a mixture of ethyl
acetate and petroleum ether .2:8) to afford the correspond-
ing pyridine derivatives.
2.62 .s, 6H), 0.90 .t, 6H, Jˆ8.1 Hz); 13C NMR .75 MHz,
CDCl3) d 167.7, 155.2, 146.1, 136.4, 128.3, 127.9, 126.8,
61.2, 22.7, 13.5; MS m/z 328 .M1); Anal. calcd for
C19H21NO4: C, 69.71; H, 6.47; N, 4.28; Found: C, 69.82;
H, 6.39; N, 4.19.
3.2. Oxidation of Hantzsch 1,4-dihydropyridines with
peroxidisulfate-CoꢀII): general procedure
3.2.6. Diethyl 2,6-dimethyl-4-ꢀm-nitrophenyl)pyridine-
3,5-dicarboxylate ꢀ20). Pale yellow colored solid; mp
60±628C .lit.,27 61±628C); IR .KBr) 3084, 2982, 2935,
1726, 1534, 1352, 1290, 1234, 1105, 1041, 737,
A solution of potassium peroxydisulphate .0.53 g, 2 mmol)
and cobalt.II) nitrate .0.58 g, 2 mmol) in 5 mL of water was
added to a solution of 1,4-dihydropyridine .2 mmol) in
20 mL of acetonitrile.excess) in a 100 mL RB ¯ask. The
resulting mixture was re¯uxed on a water bath. After ascer-
taining the completion of the reaction by TLC, the reaction
mixture was worked up as described above.
1
695 cm21; H NMR .300 MHz, CDCl3) d 8.29 .m, 1H),
8.22 .m, 1H), 7.67 .m, 2H), 4.10 .q, 4H, Jˆ7.3 Hz), 2.65
.s, 6H), 0.98 .t, 6H, Jˆ6.9 Hz); 13C NMR .75 MHz, CDCl3)
d 166.6, 155.6, 147.4, 143.1, 137.7, 134.0, 128.9, 126.1,
122.9, 61.1, 22.5, 13.2; MS m/z 373 .M1); Anal. calcd for
C19H20N2O6: C, 61.28; H, 5.41; N, 7.52; Found: C, 61.39; H,
5.49; N, 7.44.
3.2.1. Diethyl 2,6-dimethyl pyridine-3,5-dicarboxylate
ꢀ15). Colorless solid; mp 69±708C .lit.,25 70±718C); IR
.KBr) 2981, 2932, 1719, 1591, 1441, 1369, 1295, 1222,
3.2.7. Diethyl 2,6-dimethyl-4-ꢀp-nitrophenyl)pyridine-
3,5-dicarboxylate ꢀ21). Pale yellow colored solid; mp
112±1148C .lit.,28 1158C); IR .KBr) 3111, 3054, 2977,
2929, 1724, 1558, 1518, 1349, 1231, 1105, 1044, 863,
1
1120, 1043, 771, 697 cm21; H NMR .300 MHz, CDCl3)
d 8.67.s, 1H), 4.41 .q, 4H, Jˆ7.4 Hz), 2.84 .s, 6H), 1.42
.t, 6H, Jˆ7.2 Hz); 13C NMR .75 MHz, CDCl3) d 165.8,
162.1, 140.8, 122.9, 61.3, 24.8, 14.2; MS m/z 251 .M1);
Anal. calcd for C13H17NO4: C, 62.14; H, 6.82; N, 5.57;
Found: C, 62.23; H, 6.75; N, 5.48.
1
747, 702 cm21; H NMR .300 MHz, CDCl3) d 8.27.d,
2H, Jˆ8.8 Hz), 7.46 .d, 2H, Jˆ8.8 Hz), 4.04 .q, 4H,
Jˆ7.2 Hz), 2.64 .s, 6H), 0.98 .t, 6H, Jˆ7.1 Hz); 13C NMR
.75 MHz, CDCl3) d 167.1, 156.1, 147.7, 143.2, 129.3,
126.2, 123.5, 123.2, 61.6, 23.0, 13.6; MS m/z 373 .M1);
Anal. calcd for C19H20N2O6: C, 61.32; H, 5.39; N, 7.55;
Found: C, 61.35; H, 5.43; N, 7.49.
3.2.2. Diethyl 2,6-dimethyl-4-methylpyridine-3,5-dicar-
boxylate ꢀ16). Pale yellow colored oil .lit.,26 oil); IR
.KBr) 2981, 2937, 1725, 1567, 1239, 1107, 1041,
1
857cm 21; H NMR .300 MHz, CDCl3) d 4.42 .q, 4H,
3.2.8. Diethyl 2,6-dimethyl-4-ꢀp-methylphenyl)pyridine-
3,5-dicarboxylate ꢀ22). Pale yellow colored solid; mp 71±
738C .lit.,26 72±738C); IR .KBr) 2981, 2930, 2872, 1728,
Jˆ7.2 Hz), 2.53, .s, 6H), 2.28 .s, 3H), 1.40 .t, 6H,
Jˆ7.1 Hz); 13C NMR .75 MHz, CDCl3) d 168.3, 154.9,
142.3, 127.7, 61.6, 22.8, 17.0, 14.2; MS m/z 265 .M1);
Anal. calcd for C14H19NO4: C, 63.38; H, 7.22; N, 5.28;
Found: C, 63.55; H, 7.30; N, 5.21.
1
1555, 1289, 1233, 1104, 1042, 862, 822 cm21; H NMR
.300 MHz, CDCl3) d 7.16 .br s, 4H), 4.03 .q, 4H,
Jˆ7.2 Hz), 2.60 .s, 6H), 2.36 .s, 3H, ArCH3), 0.95 .t, 6H,
Jˆ7.1 Hz); 13C NMR .75 MHz, CDCl3) d 167.9, 155.2,
146.3, 138.3, 133.6, 128.8, 128.0, 127.2, 61.3, 22.8, 21.2,
13.6; MS m/z 342 .M1); Anal. calcd for C20H23NO4: C,
70.36; H, 6.79; N, 4.10; Found: C, 70.51; H, 6.70; N, 3.98.
3.2.3. Diethyl 2,6-dimethyl-4-n-propylpyridine-3,5-
dicarboxylate ꢀ17). Pale yellow colored oil; IR .KBr)
1
2959, 2933, 2873, 1727, 1566, 1234, 1106, 1040 cm21; H
NMR .300 MHz, CDCl3) d 4.41 .q, 4H, Jˆ6.8 Hz), 2.75±
2.43 .m, 2H), 2.51 .s, 6H), 1.58 .m, 2H), 1.39 .t, 6H,
Jˆ7.2 Hz), 0.93 .t, 3H, Jˆ6.0 Hz); 13C NMR .75 MHz,
CDCl3) d 168.5, 155.1, 146.1, 141.0, 127.3, 61.6, 33.5,
24.2, 22.9, 14.2; MS m/z 293 .M1); Anal. calcd for
C16H23NO4: C, 65.51; H, 7.90; N, 4.77; Found: C, 65.73;
H, 7.82; N, 4.85.
3.2.9. Diethyl 2,6-dimethyl-4-ꢀp-methoxyphenyl)pyri-
dine-3,5-dicarboxylate ꢀ23). Colorless solid; mp 56±588C
.lit.,29 57±598C); IR .KBr) 2980, 2935, 2838, 1726, 1555,
;
1444, 1180, 1105, 1040, 862, 835 cm21 1H NMR
.300 MHz, CDCl3) d 7.19 .d, 2H, Jˆ9 Hz), 6.89 .d, 2H,
Jˆ9 Hz), 4.05 .q, 4H, Jˆ7.2 Hz), 3.82 .s, 3H, OCH3),
2.59 .s, 6H), 0.99 .t, 6H, Jˆ7.3 Hz); 13C NMR .75 MHz,
CDCl3) d 168.1, 159.8, 155.2, 145.8, 129.5, 128.7, 127.3,
113.6, 61.3, 55.3, 22.8, 13.7; MS m/z 358 .M1); Anal. calcd
for C20H23NO5: C, 67.21; H, 6.49; N, 3.92; Found: C, 67.34;
H, 6.41; N, 3.83.
3.2.4. Diethyl 2,6-dimethyl-4-n-butylpyridine-3,5-dicar-
boxylate ꢀ18). Pale yellow colored oil; IR .KBr) 2966,
1
2875, 1727, 1568, 1284, 1236, 1200, 1105, 1040 cm21; H
NMR .300 MHz, CDCl3) d 4.41 .q, 4H, Jˆ6.2 Hz), 2.65±
2.58 .m, 2H), 2.51 .s, 6H), 1.58±1.20 .m, 4H), 1.39 .t, 6H,
Jˆ7.2 Hz), 0.91 .t, 3H, Jˆ7.5 Hz); 13C NMR .75 MHz,
CDCl3) d 168.5, 155.0, 146.7, 127.3, 121.5, 61.6, 33.0,
31.2, 23.1, 22.8, 14.3; MS m/z 307.M 1); Anal. calcd for
C17H25NO4: C, 66.43; H, 8.20; N, 4.56; Found: C, 66.18; H,
8.31; N, 4.65.
3.2.10. Diethyl 2,6-dimethyl-4-ꢀ2-thienyl)pyridine-3,5-
dicarboxylate ꢀ24). Light brown colored solid; mp 78±
808C .lit.,30 76±798C); IR .KBr) 3106, 2981, 2934, 1726,
1
1557, 1443, 1288, 1232, 1099, 1041, 859, 707 cm21; H
NMR .300 MHz, CDCl3) d 7.42 .br s, 1H), 7.08 .br s,
2H), 4.14 .q, 4H, Jˆ8.4 Hz), 2.61 .s, 6H), 1.07.t, 6H,
Jˆ6.1 Hz); 13C NMR .75 MHz, CDCl3) d 167.3, 147.7,
144.0, 127.9, 127.7, 126.0, 103.9, 59.6, 39.5, 19.3, 14.2;
MS m/z 334 .M1); Anal. calcd for C17H19NO4S: C, 61.24;
H, 5.74; N, 4.20; Found: C, 61.09; H, 5.85; N, 4.31.
3.2.5. Diethyl 2,6-dimethyl-4-phenylpyridine-3,5-dicar-
boxylate ꢀ19). Colorless solid; mp 63±658C .lit.,26 62±
648C); IR .KBr) 2981, 2934, 1716, 1556, 1290, 1228,
1096, 1040, 753 cm21 1H NMR .300 MHz, CDCl3) d
;
7.37 .br s, 2H), 7.27 .br s, 3H), 4.01 .q, 4H, Jˆ6.0 Hz),

M. Anniyappan et al. / Tetrahedron 58 '2002) 5069±5073
5073
2. Khadikar, B.; Borkat, S. Synth. Commun. 1998, 28, 207and
references cited therein.
3.2.11. Diethyl 2,6-dimethyl-4-ꢀ2-furyl)pyridine-3,5-
dicarboxylate ꢀ25). Yellow colored oil .lit.,31 oil); IR
.KBr) 3121, 2982, 2936, 1726, 1563, 1234, 1105, 1042,
3. Balogh, M.; Hermecz, I.; Meszaros, Z.; Laszlo, P. Helv. Chim.
Acta 1984, 67, 2270.
4. P®ster, J. R. Synthesis 1990, 689.
1
750 cm21; H NMR .300 MHz, CDCl3) d 7.56 .br s, 1H),
6.66 .br s, 1H), 6.56 .br s, 1H), 4.28 .q, 4H, Jˆ7.1 Hz), 2.60
.s, 6H), 1.22 .t, 6H, Jˆ7.2 Hz); 13C NMR .75 MHz, CDCl3)
d 167.7, 155.3, 147.6, 143.7, 133.4, 124.5, 111.7, 111.5,
61.4, 22.3, 13.6; MS m/z 318 .M1); Anal. calcd for
C17H19NO5: C, 64.14; H, 6.33; N, 4.40; Found: C, 64.32;
H, 6.24; N, 4.32.
5. Maquestiau, A.; Mayence, A.; Eynde, J.-J. V. Tetrahedron
Lett. 1991, 32, 3839.
6. Eynde, J.-J. V.; Mayence, A.; Maquestiau, A. Tetrahedron
1992, 48, 463.
7. Kurtz, J. L.; Hutton, R.; Westheimer, F. H. J. Am. Chem. Soc.
1961, 33, 584.
3.2.12. Diethyl 2,6-dimethyl-4-ꢀN-benzenesulphonyl-3-
indolyl)pyridine-3,5-dicarboxylate ꢀ26). Pale yellow
colored solid; mp 132±1358C; IR .KBr) 3100, 3064,
2986, 2934, 1728, 1560, 1448, 1373, 1234, 1186, 1107,
8. Boucher, R. H.; Guengerich, F. D. J. Med. Chem. 1986, 29,
1596.
9. Itoh, T.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron Lett.
1995, 36, 2269.
1045, 955, 725, 685, 592 cm21
;
1H NMR .300 MHz,
10. Zhu, X.-Q.; Zhao, B.-J.; Chang, J.-P. J. Org. Chem. 2000, 65,
8158.
CDCl3) d 8.05±7.91 .m, 3H), 7.62±7.18 .m, 7H), 3.71 .q,
4H, Jˆ6.5 Hz), 2.62 .s, 6H), 0.54 .t, 6H, Jˆ7.1 Hz); 13C
NMR .75 MHz, CDCl3) d 167.4, 156.0, 138.0, 137.4, 134.2,
134.0, 129.9, 129.3, 127.6, 126.9, 125.3, 124.6, 123.6,
120.8, 118.5, 113.3, 61.2, 23.0, 13.0; MS m/z 507.M 1);
Anal. calcd for C27H26N2O6S: C, 64.02; H, 5.17; N, 5.23;
Found: C, 64.24; H, 5.09; N, 5.44.
11. For reviews see: .a) Caddick, S. Tetrahedron 1995, 51, 10403.
.b) Majdoub, M.; Loupy, A.; Peter, A.; Roudesli, M. S.
Tetrahedron 1996, 52, 617. .c) Raner, K. D.; Strauss, C. R.;
Trainor, R. W.; Thorn, J. S. J. Org. Chem. 1995, 60, 2456.
.d) Baruah, B.; Boruah, A.; Prajapati, D.; Sandhu, J. S.
Tetrahedron Lett. 1997, 38, 1449. .e) Anniyappan, M.;
Muralidharan, D.; Perumal, P. T. Synth. Commun. 2002, 32,
659.
3.2.13. Diethyl 2,6-dimethyl-4-cinnamylpyridine-3,5-
dicarboxylate ꢀ27). Pale yellow colored solid; mp 163±
1658C .lit.,26 162±1658C); IR .KBr) 3059, 2981, 2935,
1727, 1556, 1448, 1372, 1237, 1107, 1041, 747,
12. .a) Mundla, S. R. Tetrahedron Lett. 2000, 41, 4277. .b) Sura,
T. P.; Ramana, M. M. V.; Kudav, N. A. Synth. Commun. 1988,
18, 2161.
1
693 cm21; H NMR .300 MHz, CDCl3) d 7.63±7.19 .m,
13. Anniyappan, M.; Nagarajan, R.; Perumal, P. T. Synth.
Commun. 2002, 32, 99.
5H), 7.12 .d, 1H, Jˆ16.5 Hz), 6.82 .d, 1H, Jˆ16.5 Hz),
4.34 .q, 4H, Jˆ7.2 Hz), 2.59 .s, 6H), 1.29 .t, 6H,
Jˆ7.1 Hz); 13C NMR .75 MHz, CDCl3) d 168.0, 155.3,
142.5, 136.8, 135.9, 128.0, 126.8, 125.8, 122.4, 119.5,
61.7, 22.6, 14.1; MS m/z 354 .M1); Anal. calcd for
C21H23NO4: C, 71.37; H, 6.56; N, 3.96; Found: C, 71.16;
H, 6.65; N, 4.07.
14. Vogel, A. I. A Textbook of Practical Organic Chemistry;
Longmans: London, 1971 p 442.
15. House, D. A. Chem. Rev. 1962, 62, 185.
16. Giordano, C.; Belli, A. J. Org. Chem. 1979, 44, 2314.
17. Heiba, E. I.; Dessau, R. M.; Koehl Jr, W. J. J. Am. Chem. Soc.
1969, 91, 6830.
18. Bhatt, M. V.; Perumal, P. T. Terahedron Lett. 1981, 22, 2605.
19. Loev, B.; Snader, K. M. J. Org. Chem. 1965, 30, 1914.
20. Ayling, E. E. J. Chem. Soc. 1938, 1014.
21. Huntress, E. H.; Shaw, E. N. J. Org. Chem. 1948, 13, 674.
22. Delgado, F.; Alvarez, C.; Garcia, O.; Penieres, G.; Marquez,
C. Synth. Commun. 1991, 21, 2137.
3.2.14. Diethyl 2,6-dimethyl-4-chrotylpyridine-3,5-dicar-
boxylate ꢀ28). Yellow colored oil; IR .KBr) 2981, 2936,
1
1724, 1565, 1444, 1235, 1108, 1041, 861 cm21; H NMR
.300 MHz, CDCl3) d 6.43 .d, 1H, Jˆ16 Hz), 6.09±5.95 .m,
1H), 4.37.q, 4H, Jˆ7.1 Hz), 2.54 .s, 6H), 1.84 .d, 3H,
Jˆ6.5 Hz), 1.36 .t, 6H, Jˆ7.2 Hz); 13C NMR .75 MHz,
CDCl3) d 167.8, 154.6, 142.1, 134.2, 125.5, 124.8, 61.2,
22.2, 18.6, 13.8; MS m/z 292 .M1); Anal. calcd for
C16H21NO4: C, 65.96; H, 7.27; N, 4.81; Found: C, 65.75;
H, 7.36; N, 4.89.
23. Ball, D. L.; Crutch®eld, M. N.; Edwards, J. O. J. Org. Chem.
1960, 25, 1599.
24. Nyberg, K.; Wistrand, L. G. J. Org. Chem. 1978, 43, 2613.
25. Engelman, F. Ann. 1885, 231, 37 .
26. Loev, B.; Snader, K. M. J. Org. Chem. 1965, 30, 1914.
27. Ko, K. Y.; Park, J. Y. Bull. Korean Soc. 1995, 16, 200.
28. Cook, A. H.; Heilbron, I. M.; Steger, L. J. Chem. Soc. 1943,
413.
Acknowledgements
29. Memarian, H. R.; Sadeghi, M. M.; Aliyan, H. Indian J. Chem.
1998, 27B, 219.
We thank Council of Scienti®c and Industrial Research,
New Delhi, India, for ®nancial support.
30. Memarian, H. R.; Sadeghi, M. M.; Momeni, A. R. Indian J.
Chem. 1999, 38B, 800.
31. Heiber, F. Ber. 1892, 25, 2405.
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