Synthesis of pyridine and 2,2′-bipyridine derivatives from the aza Diels-Alder reaction of substituted 1,2,4-triazines

Article abstract of DOI:10.1016/j.tet.2004.07.024

Amidrazone 1a and the tricarbonyl derivatives 2b-d reacted in boiling ethanol in the presence of 2,5-norbornadiene 5 giving the pyridine derivatives 6b-d respectively (59-72%) and in the presence of 2,3-dihydrofuran 7 yielding the lactones 10b-d (39-44%).

Full text of DOI:10.1016/j.tet.2004.07.024

Tetrahedron 60 (2004) 8893–8897
Synthesis of pyridine and 2,20-bipyridine derivatives from the aza
Diels–Alder reaction of substituted 1,2,4-triazines
b
a
Stephen P. Stanforth,a, Brian Tarbit and Michael D. Watson
*
aDepartment of Chemical and Life Sciences, School of Applied Sciences, University of Northumbria, Newcastle upon Tyne NE1 8ST, UK
bSeal Sands Chemicals Ltd., Seal Sands Road, Seal Sands, Middlesbrough TS2 1UB, UK
Received 10 May 2004; revised 16 June 2004; accepted 8 July 2004
Available online 23 August 2004
Abstract—Amidrazone 1a and the tricarbonyl derivatives 2b–d reacted in boiling ethanol in the presence of 2,5-norbornadiene 5 giving the
pyridine derivatives 6b–d respectively (59–72%) and in the presence of 2,3-dihydrofuran 7 yielding the lactones 10b–d (39–44%). The 2,20-
bipyridine derivatives 6e–g were similarly obtained in good yield (81–87%) from the reaction of amidrazone 1b and tricarbonyl derivatives
2b–d in the presence of 2,5-norbornadiene 5.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
dienophiles have been utilised in this reaction enabling the
preparation of a wide variety of pyridine derivatives. 1,2,4-
Triazines9 have been used as 2-azadiene equivalents on
many occasions and these heterocycles have been reacted
with suitable acetylene equivalents yielding pyridine
derivatives (Scheme 2). Recent examples of the aza
Diels–Alder reaction of 1,2,4-triazines giving pyridine
and/or 2,20-bipyridine derivatives include their reaction
with 2,5-norbornadiene10 and enamines as acetylene
equivalents.11
Pyridine derivatives occupy a pivotal position in modern
heterocyclic chemistry and consequently facile methods for
the synthesis of this ring system from readily available
starting materials is of contemporary interest.1 2,20-
Bipyridine and its derivatives have also been the subject
of numerous studies, principally because of their well
developed coordination chemistry.2 They have found
applications in many areas of chemistry including supra-
molecular chemisty,3 artificial photosynthesis systems,4
luminescent sensor materials,5 non-linear optical materials6
and when they bear pendant chiral substituents, they have
found use as ligands in metal catalysed asymmetric
reactions.7 The aza Diels–Alder reaction has become an
important and versatile method for the preparation of
pyridine derivatives and several recent reviews have
discussed the scope and application of this useful reaction.8
One important theme in aza Diels–Alder methodology is the
reaction between a 2-azadiene and a suitable dienophile to
form either the dihydro- or tetrahydro-pyridine skeleton as
depicted in Scheme 1. A diverse range of 2-azadienes and
Scheme 2.
1,2,4-Triazines can be readily prepared from 1,2-dicarbonyl
derivatives and amidrazones [RC(ZNHNH2)NH2] and
many 1,2,4-triazines have been prepared using this
methodology.9 The 1,2-dicarbonyl compounds that have
been used in this reaction have generally been symmetrical
and problems with the formation of regioisomeric triazines
cannot occur. a-Ketoaldehydes also react with amidrazones
giving single products derived from attack of the
amidrazone’s hydrazine group at the aldehyde carbonyl
group. The reaction of amidrazones with symmetrical 1,2,3-
triketones similarly yields 1,2,4-triazine derivatives. Inter-
estingly, only a few examples of the reaction of amidrazones
with a,b-diketoesters have been reported (Scheme 3). Thus,
the reaction between the amidrazone 1c and the ester 2d was
Scheme 1.
Keywords: Pyridines; 2,20-Bipyridines; Aza Diels–Alder reaction; 1,2,4-
Triazines.
* Corresponding author. Tel.: C44-191-2274784; fax: C44-191-2273519;
e-mail: steven.stanforth@unn.ac.uk
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.024

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S. P. Stanforth et al. / Tetrahedron 60 (2004) 8893–8897
Scheme 3.
reported to give only ethyl 3,5-diphenyl[1,2,4]triazine-6-
carboxylate 3i in 70% yield12 whereas Ohsumi and
Neunhoeffer reacted this amidrazone 1c with ester 2a and
obtained a mixture of the corresponding regioisomeric
triazines 3h and 4h in unspecified yields.13 The reaction of
amidrazone 1a with ester 2a was investigated by Synder and
co-workers who obtained a 10.5:1 mixture of the regio-
isomeric triazines 3a and 4a in 46% overall yield.14 An a,b-
diketoester bearing a pendant protected amino acid moiety
has been reacted with S-methylisothiosemicarbazide 1d
giving a mixture of regioisomeric triazines in low overall
yield.15Thus, the reactions between amidrazones and a,b-
diketoester 2a gave mixtures of 1,2,4-triazines whereas only
one 1,2,4-triazine product was obtained when a more
sterically demanding R2 group was present i.e. the a,b-
diketoester 2d was used.
developed as a useful method for the preparation of pyridine
and bipyridine derivatives via the aza Diels–Alder reaction
of 1,2,4-triazine intermediates.
2. Results and discussion
Amidrazone 1a (prepared from ethyl thioamido oxalate16
and hydrazine hydrate) and compound 2b reacted in boiling
ethanol in the presence of an excess of 2,5-norbornadiene 5
to give a single pyridine derivative, compound 6b, in 78%
yield. Under similar conditions, the pyridine derivatives 6c
(72%) and 6d (59%) were prepared from the appropriate
a,b-diketoesters and 2,5-norbornadiene 5. We assumed that
the amidrazone 1a had reacted regioselectively with the a,b-
diketoesters 2b–d yielding the corresponding triazine
intermediates 3b–d and not the isomeric heterocycles
4b–d. This assumption was confirmed by selective
hydrolysis of the less sterically crowded 6-ester substituent
in pyridines 6b and 6d and subsequent decarboxylation
In view of the current interest in pyridine and 2,20-
bipyridine synthesis, we envisaged that the reaction of
amidrazones 1a16 and 1b17 with a,b-diketoesters 218 in the
presence of an appropriate aza-dienophile might be
Scheme 4.

S. P. Stanforth et al. / Tetrahedron 60 (2004) 8893–8897
8895
yielding the known ethyl 2-propylpyridine-3-carboxylate19
and ethyl 2-phenylpyridine-3-carboxylate20 respectively.
2b–d in the presence0 of 2,5-norbornadiene 5 giving
pyridines 6b–d and 2,2 -bipyridines 6e–g in good overall
yields and that lactones 10b–d could be prepared in
moderate overall yields from amidrazone 1a and a,b-
diketoesters 2b–d in the presence of 2,3-dihydrofuran 7.
The methodology described above for the synthesis of
pyridines 6b–d was readily extended to the preparation of
the bipyridine derivatives 6e–g. Thus, amidrazone 1b was
reacted with each of the a,b-diketoesters 2b–d in the
presence of an excess of 2,5-norbornadiene 5 in boiling
ethanol yielding the bipyridines 6e (81%), 6f (80%) and 6g
(87%) respectively.
3. Experimental
Amidrazone 1a was prepared from ethyl thioamido oxalate
[EtO2CC(ZS)NH2]
16
and hydrazine hydrate. Ethyl thio-
amido oxalate was prepared from commercially available
ethyl oxamate and Lawesson’s reagent following a
literature proceedure.16 Amidrazone 1b was prepared from
2-cyanopyridine and hydrazine hydrate.17 1H NMR spectra
were determined at 270 MHz.
2,3-Dihydrofuran 7 has been used by Gilchrist and
co-workers21 as an acetylene equivalent in the aza Diels–
Alder reaction of triazines. Amidrazone 1a was reacted with
each of the a,b-diketoesters 2b–d and an excess of 2,3-
dihydrofuran 7 in ethanol at reflux in a ‘one-pot’ reaction
yielding the lactones 10b (44%), 10c (44%) and 10d (39%)
respectively as shown in Scheme 4. Ring-opening of the
ether ring in intermediates 8 yields the pyridines 9 which
could not be isolated but underwent lactonisation giving the
products 10b–d. The proposed regioselectivity depicted in
formula 8 was confirmed by starting with the methyl ester
analogue of the a,b-diketoester 2b. Reaction of this
compound with the amidrazone 1a in the presence of 2,3-
dihydrofuran 7 gave the methyl ester analogue of lactone
10b, compound 11, indicating that the 2-ester substituent in
the triazine intermediate 3b was involved in lactonisation.
3.1. Synthesis of pyridines 6b–d and 10b–d. General
method
To a stirred solution ethyl thioamido oxalate16 (0.5 g,
3.75 mmol) in ethanol (25 mL) was added hydrazine
hydrate (0.19 g, 3.75 mmol). After 20 min at room tem-
perature, the appropriate a,b-diketoester 218 (3.75 mmol)
and either 2,5-norbornadiene 5 (3.46 g, 37.5 mmol) or 2,3-
dihydrofuran 7 (7.9 g, 133 mmol) were added in one
portion. The solution was heated at reflux for 20 h, allowed
to cool to room temperature and the solvent was evaporated
under reduced pressure. The product was isolated by
columchromatography over silica gel.
The observed regioselectivity of the cycloaddition of
triazine 3b and 2,3-dihydrofuran 7 was also predicted by
PM3 semi-empirical molecular orbital calculations
(Fig. 1).22 The HOMO (2,3-dihydrofuran)/LUMO (triazine)
energy difference (8.21 eV) is significantly smaller than the
HOMO (triazine)/LUMO (2,3-dihydrofuran) energy differ-
ence (11.50 eV) indicating that the former interaction will
determine the outcome of this inverse electron demand
cycloaddition reaction. The coefficients of the HOMO (2,3-
dihydrofuran)/LUMO (triazine) at the reaction centres are
shown in Figure 1. The most efficient frontier molecular
orbital overlap will occur when the largest frontier
molecular orbital coefficients of the two reactants interact
and this corresponds to the C3-position of the 2,3-
dihydrofuran 7 interacting with the C2-position of the
triazine 3b and the C2-position of the 2,3-dihydrofuran 7
interacting with the C5-position of the triazine 3b. This
situation corresponds with the observed regioselectivity of
the cycloaddition reaction.
3.1.1. Diethyl 6-propylpyridine-2,5-dicarboxyate 6b.
This compound was obtained as an orange oil (78%)
(eluent: ethyl acetate/petroleum ether bp 60–80 8C 1:1). 1H
NMR: (CDCl3) d 8.23 (d, 1H, JZ8 Hz, py-H), 7.97 (d, 1H,
JZ8 Hz, py-H), 4.49–4.40 (overlapping quartets, 4H, 2!
ester-CH2–), 3.19 (t, 2H, JZ7 Hz, –CH2–), 1.75 (sextet, 2H,
JZ7 Hz, –CH2–), 1.44 (overlapping triplets, 6H, 2!ester-
CH3) and 0.95 (t, 3H, JZ7 Hz, –CH3) ppm, HRMS (CI):
calcd for C14H20NO4 (MCH) 266.1392, found 266.1392.
3.1.2. Diethyl 6-isopropylpyridine-2,5-dicarboxyate 6c.
This compound was obtained as an orange oil (72%)
(eluent: ethyl acetate/petroleum ether bp 60–80 8C 1:1). 1H
NMR: (CDCl3) d 8.12 (d, 1H, JZ8 Hz, py-H), 7.92 (d, 1H,
JZ8 Hz, py-H), 4.42 (overlapping quartets, 4H, 2!ester-
CH2–), 3.77 (septet, 1H, JZ7 Hz, –CH–), 1.43 (overlapping
triplets, 6H, 2!ester-CH3) and 1.35 (d, 6H, JZ7 Hz, 2!-
CH3) ppm, HRMS (CI): calcd for C14H20NO4 (MCH)
266.1392, found 266.1388.
3.1.3. Diethyl 6-phenylpyridine-2,5-dicarboxylate 6d.
This compound was obtained as a yellow oil (59%) (eluent:
1
ethyl acetate/petroleum ether bp 60–80 8C 4:6). H NMR:
(CDCl3) d 8.19 (d, 1H, JZ8 Hz, py-H), 8.10 (d, 1H, JZ
8 Hz, py-H), 7.57 (m, 1H, Ph-H), 7.44 (m, 4H, Ph-H), 4.49
(q, 2H, JZ7 Hz, –CH2–), 4.17 (q, 2H, JZ7 Hz, –CH2–),
1.45 (t, 3H, JZ7 Hz, –CH3) and 1.05 (t, 3H, JZ7 Hz,
–CH3) ppm, HRMS (CI): calcd for C17H18NO4 (MCH)
300.1124, found 300.1234.
Figure 1.
In conclusion we have developed a useful ‘one pot’ method
for the preparation of pyridine and 2,20-bipyridine deriva-
tives from a,b-diketoesters 2b–d under mild conditions.
Thus, we have shown that amidrazones 1a and 1b reacted in
boiling ethanol with unsymmetrical tricarbonyl derivatives
3.1.4. Ethyl/methyl 8-oxo-2-propyl-5,6-dihydro-8H-
pyrano[3,4-b]pyridine-3-carboxylate 10b/11. This

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S. P. Stanforth et al. / Tetrahedron 60 (2004) 8893–8897
compound was obtained as an orange oil (44%) (eluent,
petroleum ether bp 60–80 8C/ethyl acetate 4:6). nmax (KBr):
for the preparation of ethyl 2-phenylpyridine-3-carboxylate
and was obtained as a brown oil. 1H NMR: (CDCl3) d 8.67
(dd, 1H, JZ5, 2 Hz, py-H), 8.17 (dd, 1H, JZ8, 2 Hz, py-H)
7.24 (dd, 1H, JZ8, 2 Hz, py-H), 4.40 (q, 2H, JZ7 Hz, ester-
CH2–) 3.14 (t, 2H, JZ7 Hz, –CH2–), 1.76 (m, 2H, –CH2–),
1.41 (t, 3H, JZ7 Hz, ester-CH3) and 1.00 (t, 3H, JZ7 Hz,
1
1724 and 1187 cmK1. H NMR: (CDCl3) d 8.08 (s, 1H,
py-H), 4.60 (t, 2H, JZ6 Hz, ring-CH2–), 4.43 (q, 2H, JZ
7 Hz, ester-CH2–), 3.17 (overlapping triplets, 5H, ester-
CH3, ring-CH2–), 1.72 (m, 2H, –CH2–), 1.43 (t, 2H, JZ
7 Hz, –CH2–) and 0.99 (t, 3H, JZ7 Hz, –CH3) ppm, 13C
NMR: (CDCl3) d 165.9 (CO), 163.4 (CO), 162.3 (C), 143.8
(C), 138.2 (CH), 132.9 (C), 129.5 (C), 66.9 (CH3), 62.1
(CH3), 38.7 (CH2), 29.7 (CH2), 26.9 (CH2), 23.6 (CH2) and
14.2 (CH2) ppm, HRMS (CI): calcd for C14H18NO4 (MCH)
264.1236, found 264.1234. When the experiment was
repeated using methyl 2,3-dioxohexanoic acid in place of
compound 2b, the methyl ester 11 was obtained which had
the following 1H NMR spectral data (CDCl3): d 8.09 (s, 1H,
py-H), 4.60 (t, 2H, JZ7 Hz, ring-CH2–), 3.96 (s, 3H, –CH3),
3.16 (m, 4H, 2!-CH2–), 1.72 (sextet, 2H, JZ7 Hz, –CH2–)
and 0.98 (t, 3H, JZ7 Hz, –CH3) ppm.
1
–CH3) ppm. This H NMR spectral data is consistent with
that reported in the literature.19
3.1.8. 6-Phenylpyridine-2,5-dicarboxylic acid 5-ethyl
ester and ethyl 2-phenylpyridine-3-carboxylate. To a
solution of diethyl 6-phenylpyridine-2,5-dicarboxylate 6d
(0.3 g, 1.00 mmol) in ethanol (20 mL) was added a solution
of KOH (0.12 g, 1.00 mmol, in 2 mL of water) and the
mixture was stirred at room temperature for 3 h. The pH was
then adjusted to 1 and the mixture was extracted with
dichloromethane (25 mL), washed with water (2!5 mL)
and evaporated to give the 6-phenylpyridine-2,5-di-
carboxylic acid 5-ethyl ester as a brown oil (0.22 g, 81%).
1H NMR: (CDCl3) d 8.32 (d, 1H, JZ8 Hz, py-H), 8.27 (d,
1H, JZ8 Hz, py-H), 7.53–7.48 (m, 5H, Ph-H), 4.20 (q, 2H,
JZ7 Hz, ester-CH2–) and 1.08 (t, 3H, JZ7 Hz, ester-CH3)
ppm. 6-Phenylpyridine-2,5-dicarboxylic acid 5-ethyl ester
(0.22 g, 0.81 mmol) was placed in a round bottom flask and
heated gently by means of a Bunsen burner for 2 min. The
resulting distillate was collected giving ethyl 2-phenyl-
3.1.5.
Ethyl
8-oxo-2-isopropyl-5,6-dihydro-8H-
pyrano[3,4-b]pyridine-3-carboxylate 10c. The ethyl
ester was obtained as an orange oil (44%) (eluent: petroleum
ether bp 60–80 8C/ethyl acetate 4:6). nmax (KBr): 1722 and
1187 cmK1. 1H NMR: (CDCl3) d 7.94 (s, 1H, py-H), 5.85 (t,
2H, JZ6 Hz, ring-CH2–), 4.42 (q, 2H, JZ7 Hz, ester-
CH2–), 3.74 (septet, 1H, –CH–), 3.13 (t, 2H, JZ6 Hz, ring-
CH2–), 1.43 (t, 3H, JZ7 Hz, ester-CH3) and 3.39 (d, 6H,
JZ7 Hz, 2!isopropyl-CH3) ppm, 13C NMR: (CDCl3) d
167.0 (CO), 166.4 (CO), 162.2 (C), 143.8 (C), 137.4 (CH),
132.8 (C), 129.4 (C), 66.8 (–CH3), 62.1 (CH3), 32.9 (CH2),
27.0 (CH2), 22.2 (CH2), 21.1 (CH2) and 14.2 (CH2) ppm,
HRMS (CI): calcd for C14H18NO4 (MCH) 264.1236, found
264.1233.
1
pyridine-3-carboxylate as a brown oil (0.08 g, 42%). H
NMR: (CDCl3) d 8.76 (dd, 1H, JZ5, 2 Hz, py-H), 8.10 (dd,
1H, JZ8, 2 Hz, py-H), 7.50–7.54 (m, 2H, Ph-H), 7.40–7.44
(m, 3H, Ph-H), 7.34 (dd, 1H, JZ8, 5 Hz, py-H), 4.14 (q, 2H,
JZ7 Hz, ester-CH2–) and 1.04 (t, 3H, JZ7 Hz, ester-CH3)
1
ppm. This H NMR spectral data is consistent with that
reported in the literature.20
3.2. Synthesis of bipyridine derivatives 6e–g. General
method
3.1.6. Ethyl 8-oxo-2-phenyl-5,6-dihydro-8H-pyrano[3,4-
b]pyridine-3-carboxylate 10d. This compound was
obtained as a an orange oil which crystallised from ethanol
giving a white crystalline solid (39%), mp 162 8C. nmax
To a stirred solution of amidrazone 1b17 (0.5 g, 3.68 mmol)
in ethanol (15 mL) was added appropriate a,b-diketoester
218 (3.38 mmol) and 2,5-norbornadiene 5 (3.46 g,
36.8 mmol). This solution was heated at reflux under an
atmosphere of nitrogen for 20 h, allowed to cool to room
temperature, and evaporated under reduced pressure giving
the crude product which was purified by column chroma-
tography over silica gel.
(KBr): 1736, 1701, 1182 and 1139 cmK1 1H NMR:
.
(CDCl3) d 8.01 (s, 1H, py-H), 7.60 (m, 1H, Ph-H), 7.40
(m, 4H, Ph-H), 4.65 (t, 2H, JZ5 Hz, ring-CH2–), 4.19 (q,
2H, JZ7 Hz, ester-CH2–), 3.22 (t, 2H, JZ5 Hz, ring-CH2–)
and 1.03 (t, 3H, JZ7 Hz, ester-CH3) ppm, 13C NMR:
(CDCl3) d 167.4 (CO), 161.9 (CO), 158.8 (CH), 143.5 (C),
138.8 (C), 137.6 (CH), 133.8 (C), 131.0 (C), 129.2 (C),
128.8 (C), 128.3 (C), 66.8 (CH3), 62.1 (CH2), 27.1 (CH2)
and 13.6 (CH2) ppm, Anal. for C17H15NO4: calcd C, 68.68;
H, 5.09; N, 4.71, found C, 68.54; H, 4.84; N, 4.60.
3.2.1. Ethyl 6-propyl-2,20-bipyridine-5-carboxylate 6e.
This compound was obtained as an orange oil (81%)
(eluent: ethyl acetate/petroleum ether bp 60–80 8C 1:1).
nmax (KBr): 1718, 1252 and 1093 cmK1. 1H NMR: (CDCl3)
d 8.70 (dd, 1H, JZ5, 2 Hz, py-H), 8.52 (d, 1H, JZ8 Hz,
py-H), 8.28 (s, 2H, py-H), 7.84 (dt, 1H, JZ8, 2 Hz, py-H),
7.33 (m, 1H, py-H), 4.40 (q, 2H, JZ7 Hz, ester-CH2–), 3.22
(m, 2H, –CH2–), 1.83 (sextet, 2H, JZ7 Hz, –CH2–), 1.43 (t,
3H, JZ7 Hz, ester-CH3) and 1.04 (t, 3H, JZ7 Hz, –CH3)
ppm, HRMS (CI): calcd for C16H19N2O2 (MCH) 271.1446,
found 271.1443.
3.1.7. 6-Propylpyridine-2,5-dicarboxylic acid 5-ethyl
ester and ethyl 2-propylpyridine-3-carboxylate.
6-Propylpyridine-2,5-dicarboxylic acid 5-ethyl ester
(0.15 g, 56%) was synthesised from diethyl 6-propyl-
pyridine-2,5-dicarboxylate 6b following the procedure
described below for the preparation of 6-phenylpyridine-
2,5-dicarboxylic acid 5-ethyl ester and was obtained as a
brown oil. 1H NMR: (CDCl3) d 8.40 (d, 1H, JZ8 Hz, py-H),
8.12 (d, 1H, JZ8 Hz, py-H), 4.44 (q, 2H, JZ7 Hz, ester-
CH2–), 3.18 (t, 2H, JZ7 Hz, –CH2–), 1.08 (m, 2H, –CH2–)
1.43 (t, 3H, JZ7 Hz, ester-CH3) and 1.02 (t, 3H, JZ7 Hz,
–CH3). Ethyl 2-propylpyridine-3-carboxylate (0.17 g, 70%)
was synthesised from 6-propylpyridine-2,5-dicarboxylic
acid 5-ethyl ester following the procedure described below
3.2.2. Ethyl 6-isopropyl-2,20-bipyridinyl-5-carboxylate
6f. This compound was obtained as an orange waxy solid
(80%), mp 66–70 8C, (eluent: ethyl acetate/petroleum
1
ether bp 60–80 8C 1:1). H NMR: (CDCl3) d 8.69 (d, 1H,
JZ5 Hz, py-H), 8.59 (d, 1H, JZ8 Hz, py-H), 8.28 (d, 1H,

S. P. Stanforth et al. / Tetrahedron 60 (2004) 8893–8897
8897
ˇ
´
Meghani, P.; Kocovsku, P. J. Org. Chem. 2003, 68,
4727–4742.
JZ8 Hz, py-H), 8.20 (d, 1H, JZ8 Hz, py-H), 7.85 (t, 1H,
JZ8 Hz, py-H), 7.32 (m, 1H, py-H), 4.40 (q, 2H, JZ7 Hz,
ester-CH2–) 3.93 (septet, 1H, JZ7 Hz, –CH–), 1.42 (t, JZ
7 Hz, ester-CH3) and 1.38 (d, 6H, JZ7 Hz, 2!isopropyl-
CH3) ppm, HRMS (CI): calcd for C16H19N2O2 (MCH)
271.1446, found 271.1445.
8. (a) Behforouz, M.; Ahmadian, M. Tetrahedron 2000, 56,
5259–5288. (b) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron
2001, 57, 6099–6138. (c) Jayakumar, S.; Ishar, M. P. S.;
Mahajan, M. P. Tetrahedron 2002, 58, 379–471. (d) Boger,
D. L. Tetrahedron 1983, 39, 2869–2939.
3.2.3. Ethyl 6-phenyl-2,20-bipyridine-5-carboxylate 6g.
This compound was obtained as an orange oil (87%)
(eluent: ethyl acetate/petroleum ether bp 60–80 8C 6:4).
nmax (KBr): 1717, 1250 and 1092 cmK1. 1H NMR: (CDCl3)
d 8.70 (ddd, 1H, JZ5, 2, 1 Hz, py-H), 8.57 (dd, 1H, JZ7,
2 Hz, py-H), 8.45 (d, 1H, JZ8 Hz, py-H), 8.23 (d, 1H, JZ
8 Hz, py-H), 7.8 (dt, 1H, JZ8 Hz, py-H), 7.67–7.63 (m, 1H,
Ph-H), 7.49–7.43 (m, 4H, Ph-H), 7.33 (m, 1H, py-H), 4.40
(q, 2H, JZ7 Hz, –CH2–) and 1.09 (t, 3H, JZ7 Hz, –CH3)
ppm, HRMS (CI): calcd for C19H16N2O2 (MCH) 305.1290,
found 305.1289.
9. Neunhoeffer, H.; Katritzky, A. R., Rees, C. W., Scriven,
E. F. V., Eds.; Comprehensive Heterocyclic Chemistry II; Vol.
6. Pergamon: New York; 1996. p. 507–573. Chapter 6.11 and
references therein.
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6687–6690. (b) Pabst, G. R.; Schmid, K.; Sauer, J.
Tetrahedron Lett. 1998, 39, 6691–6694. (c) Pabst, G. R.;
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Acknowledgements
We thank Seal Sands Chemicals Ltd. for generous financial
support and the EPSRC mass spectrometry service for high
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1
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