Synthesis of 5,5′-dialkyl-6,6′-dichloro-2, 2′-bipyridines

Article abstract of DOI:10.1080/00397910802440348

5,5′-Dialkyl-6,6′-dichloro-2,2′-bipyridines were synthesized starting from 3-substituted 2-chloro-6-iodopyridines using Pd-catalyzed coupling conditions. 6-Alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones were excellent precursors for the synthesis of these functionalized 2-iodo-6-chloropyridines. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802440348

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Synthesis of 5,5′-Dialkyl-6,6′-
dichloro-2, 2′-bipyridines
N. P. Chandia a , J. C. Canales a , I. Azocar a , S.
Vanlaer b , V. G. Pawar b , W. M. De Borggraeve b , J.
Costamagna a & W. Dehaen b
a Universidad de Santiago de Chile , Alameda,
Santiago, Chile
b K. U. Leuven, Molecular Design and Synthesis ,
Leuven, Belgium
Published online: 29 Jan 2009.
To cite this article: N. P. Chandia , J. C. Canales , I. Azocar , S. Vanlaer , V. G.
Pawar , W. M. De Borggraeve , J. Costamagna & W. Dehaen (2009) Synthesis of 5,5′-
Dialkyl-6,6′-dichloro-2, 2′-bipyridines, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:5, 927-939, DOI:
10.1080/00397910802440348
To link to this article: http://dx.doi.org/10.1080/00397910802440348
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Synthetic Communications1, 39: 927–939, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802440348
Synthesis of 5,50-Dialkyl-6,60-dichloro-2,
20-bipyridines
N. P. Chandia,1 J. C. Canales,1 I. Azocar,1 S. Vanlaer,2
V. G. Pawar,2 W. M. De Borggraeve,2 J. Costamagna,1
and W. Dehaen2
1Universidad de Santiago de Chile, Alameda, Santiago, Chile
2K. U. Leuven, Molecular Design and Synthesis, Leuven, Belgium
Abstract: 5,50-Dialkyl-6,60-dichloro-2,20-bipyridines were synthesized starting
from 3-substituted 2-chloro-6-iodopyridines using Pd-catalyzed coupling condi-
tions. 6-Alkyl-3,5-dichloro-2H-1,4-oxazin-2-ones were excellent precursors for
the synthesis of these functionalized 2-iodo-6-chloropyridines.
Keywords: Coupling, Diels–Alder reactions, heterocycles, ligands, pyridines
INTRODUCTION
Methods to synthesize 2,20-bipyridine derivatives have gained increasing
importance in part because of the presence of these compounds in many
natural products, including caerulomycins, the collismycins, and camp-
tothecin and its derivatives, which are used in cancer therapy.[1] On the
other hand, bipyridines are extensively used as ligands in transition-metal
coordination compounds and exhibit various interesting characteristics.
They are used, for example, as building blocks in the assembly of sup-
ramolecular and macromolecular devices, in studies on their photochemi-
cal and electrochemical behavior, as well as for their application in
Received July 16, 2008.
Address correspondence to W. M. De Borggraeve, K. U. Leuven, Molecular
Design and Synthesis, Celestijnenlaan 200F, B-3001, Leuven, Belgium. E-mail:
Wim.DeBorggraeve@chem.kuleuven.be
927

928
N. P. Chandia et al.
catalysis.[2] 6,60-Dichloro-2,20-bipyridine was recently used as ligand in a
ruthenium-catalyzed addition of b-diketones to alcohols and styrenes.[3]
Several synthetic strategies have been devised over the years to
improve the formation of 2,20-bipyridine derivatives. The generally used
method is the metal-catalyzed coupling of pyridines, substituted pyri-
dines, or halopyridines to form the desired 2,20-bipyridines. Most of the
reactions require bromides, iodides, or triflates as coupling components,
and these are often not easily accessible but necessary to provide satisfy-
ing yields.[1]
In the framework of a project concerning the formation of hexa-
azamacrocycles where we wanted to study the influence of different alkyl
chains on the properties of the macrocycles,[4] we needed access to 5,50-
dialkyl-6,60-dichloro-2,20-bipyridines 1 (Fig. 1). Moreover, these com-
pounds could also be of interest as ligands for the ruthenium-catalyzed
reactions mentioned earlier.
Initially we planned to synthesize these compounds via double Diels–
Alder reaction=retro Diels–Alder reaction on bipyrazinones 2, which can
be easily synthesized starting from dichloropyrazinones 3 (Fig. 1). The
reaction seems to stop after the first Diels–Alder=retro Diels–Alder step.
However, this strategy failed because the bipyrazinones did not prove to
Figure 1. Retrosynthesis of 5,50-dialkyl-6,60-dichlorobipyridines.

5,50-Dialkyl-6,60-dichloro-2,20-bipyridines
929
Figure 2. Bis-halogenated pyridines.
be reactive enough to undergo reaction to the bipyridine stage.[5] As an
alternative we proposed to synthesize the bipyridines using metal-
catalyzed chemistry.
The original idea was to do homocoupling of dichloro-pyridines 5a.
It was assumed that sterical hindrance of the alkyl substituent would
favor reaction of the 6-position. When trying the reaction conditions
referred to further on in this paper for the synthesis of the target com-
pounds with the commercially available 2,6-dichloro-3-methyl-pyridine,
we were not succesful in obtaining the homocoupled compound. All
starting material was consumed, and on thin-layer chromatography
(TLC), many new spots appeared that were not further identified. These
problems were assumed to be due to lack of reactivity of the 6-chloro-
atom toward organometallic reactions.
For this kind of coupling reaction, it would be more favorable
to synthesize chloro-iodopyridines of type 4 (Fig. 1). Moreover, this
scaffold 4 would complement the known arsenal of 3-alk(en)yl-2,6-
dihalopyridines previously described in literature (Fig. 2): in compounds
5a, 5b, and c,[6,7] two equal halogen atoms are present, and in compounds
6,[8] two halogens of different reactivity toward cross coupling-chemistry
are present (X more reactive than X0). Compounds 4a–c are expected
to show inverse selectivity in cross-coupling reactions compared to
compounds 6, making them valuable tools in organic synthesis.
Figure 3. Dichloro-oxazinones.

930
N. P. Chandia et al.
Scheme 1. Reagents and conditions: (a) oxalyl chloride, chlorobenzene, rt; (b)
NaI, acetone, CSA (cat).
To obtain the asymmetric halogen substitution pattern in the pyri-
dine 4, we used a workaround via oxazinone chemistry.[9,10] It is well
known that the 3-chlorine atom in dichlorooxazinones 7 is more reactive
because it is part of an imidoyl chloride system. Hence, it can be substi-
tuted by a number of nucleophiles in the presence of an acid catalyst.[11]
Moreover, the oxazinones contain an azadiene system and can be con-
verted into pyridines by means of Diels–Alder reaction=retro Diels–Alder
reaction with an appropriate alkyne.[7,10]
The oxazinones 7a–c (Fig. 3) were readily synthesized by reacting the
corresponding cyanohydrins 8a–c with oxalylchloride in chlorobenzene
(Scheme 1, Table 1). The cyanohydrins were obtained from commercial
sources or synthesized according to general literature procedures.
The cyclization to the oxazinone 7c gave very low yields because
(uncharacterized) by-products are formed according to TLC and electro-
spray ionization-mass spectrometry (EI-MS).
In a following reaction step, the 3-chlorine atom was quantitatively
exchanged by an iodine atom using Finkelstein conditions with NaI
and a catalytic amount of camphorsulphonic acid to activate the imidoyl
chloride (Scheme 1, Table 1). The products were isolated by extraction
with EtOAc and washed with Na2S2O3 solution to remove I2. Evapora-
tion of the dried organic layer (MgSO4) yielded the pure compounds in
good yields.
Table 1. Yields of the oxazinones
Yield (%)
R
7
9
a
b
c
Methyl
Propyl
Undecyl
81
91
9
73
78
80

5,50-Dialkyl-6,60-dichloro-2,20-bipyridines
931
Scheme 2. Reagents and conditions: norbornadiene (3 eq.), toluene, 140 ꢀC.
The chloro-iodooxazinones 9a–c were converted to the correspond-
ing pyridines 4a–c by reacting them in toluene in a steel bomb with 3
equivalents of 2,5-norbornadiene, which acts as an acetylene transfer
reagent (Scheme 2, Table 2). At 140 ꢀC, the Diels–Alder adduct formed
further undergoes retro Diels–Alder reaction and loses both cyclopenta-
diene and carbon dioxide to produce the pyridines 4a–c. The reaction
speed increases in parallel with the size of the substituent on the oxazi-
none (conversion to 4c complete after 13 h, conversion to 4a complete
after 36 h). The desired pyridines were purified by column chromatogra-
phy and obtained in moderate yields of 32 to 56%.
For the conversion of these compounds to bipyridines, we tried a
number of procedures using different metal-catalyzed reactions reported
in literature (Scheme 3 and Table 3).[1] In all cases tested, as expected, the
coupling was selective for the iodine atom. An Ullmann coupling with
copper[12] and a nickel-catalyzed variant of this reaction[13] gave poor
yields of the desired compounds and were not suitable for generating
large amounts of the bipyridines. The yields for the reaction with bispina-
colatodiboron were hard to reproduce and fluctuated too much to be
useful.[5,14] We used our conditions reported for the synthesis of bipyra-
zinones to generate the bipyridines. See Ref. 5. Finally, we found that the
convenient method described by Hassan et al.[15] with Pd(OAc)2 as a
catalyst gave good yields for the synthesis of compound 1a. Using this
procedure, we were also able to synthesize the target bipyridines 1b
and 1c in acceptable and reproducible yields.
Table 2. Yields of the pyridines
Compound
R
Yield (%)
4a
4b
4c
Methyl
Propyl
Undecyl
56
51
39

932
N. P. Chandia et al.
Scheme 3. Reagents and conditions: (a) 5 eq Cu bronze, DMF, 115 ꢀC; (b) 0.2 eq
NiCl2(PPh3)2, 0.2 eq PPh3, 3 eq Zn, 3 eq NaH, 0.1 eq Bu4NI, toluene, 90 ꢀC; (c)
1 eq bispinacolatodiboron, 3 eq K2CO3, 3% Pd(PPh3)4; (d) 0.05 eq Pd(OAc)2, 1 eq
K2CO3, 0.5 eq. Bu4NBr, DMF=H2O=i-PrOH, 115 ꢀC.
EXPERIMENTAL
Apparatus and Procedures
Melting points were taken using an Electrothermal IA 9000 digital
melting-point apparatus and were uncorrected. Mass spectra were run
using a Hewlett Packard MS-Engine 5989 A apparatus for EI spectra,
and a Kratos MS50TC instrument for exact mass measurements per-
formed in the EI mode at a resolution of 10,000. NMR spectra were
recorded on a Bruker Avance 300 and a Bruker AMX 400 spectrometer.
1
NMR spectra were recorded in CDCl3 with H and 13C chemical shifts
reported in parts per million (ppm) relative to TMS.
Synthesis of 2-Hydroxybutanenitrile 8b[9]
NaHSO3 (0.1 mol) was dissolved in water (50 mL), and at 0 ꢀC butyralde-
hyde (0.05 mol) was added. Then, KCN (0.2 mol) in water (100 mL) was
added dropwise over 30 min, and the mixture was stirred for 1 h at 0 ꢀC.
Table 3. Yields of the bipyridines formed
Compound
R
Method
Yield (%)
1a
1a
1a
1a
1b
1c
Methyl
Methyl
Methyl
Methyl
Propyl
Undecyl
a
b
c
d
d
d
<5
18
57a
84
59
54
aYield is very variable in this method.

5,50-Dialkyl-6,60-dichloro-2,20-bipyridines
933
The mixture was extracted three times with chloroform, the combined
organic layers were dried over MgSO4, and the solvent was evaporated
under reduced pressure. The colorless liquid obtained was dried under
high vacuum.
Yield: 95%; liquid; dH [300 MHz, CDCl3]: 4.47 (t, 1H, J ¼ 6.8 Hz),
3.81 (s, OH), 1.82 (m, 2H), 1.54 (m, 2H), 0.98 (t, 3H, J ¼ 7.3 Hz) ppm;
dc [100 MHz, CDCl3]: 120.2 (CN), 60.9 (CH), 37.0 (CH2), 17.9 (CH2),
13.3 (CH3) ppm.
Synthesis of 2-Hydroxytridecanenitrile 8c[16]
Trimethylsilylcyanide (0.0944 mol) was added to a mixture of dodecylal-
dehyde (0.0787 mol) and BF3-Et2O (0.0944 mol) in chloroform (100 mL)
and dichloromethane (400 mL) in an acetone–dry ice bath under argon
atmosphere. The reaction mixture was poured in HCl solution (2 N,
10 mL) dropwise and was stirred for 12 h at room temperature. The
resulting mixture was poured in ether (400 mL) and washed three times
with NaHCO3 and brine. The organic layer was dried over MgSO4 and
concentrated under reduced pressure. The oil obtained was purified by
flash chromatography (silica gel, 95% CH2Cl2=5% EtOAc). The solvent
was evaporated under vacuum, and the product was dried under high
vacuum.
Yield: 82%; oil; dH [300 MHz, CDCl3]: 4.46 (t, 1H, J ¼ 7.3 Hz),
3.81 (s, OH), 1.85 (m, 2H), 1.50 (m, 2H), 1.26 (s, 16H), 0.88 (t, 3H,
J ¼ 6.7 Hz) ppm; dc [100 MHz, CDCl3]: 120.1 (CN), 61.2 (CH), 35.2
(CH2), 31.9 (2 ꢁ CH2), 30–28.8 (4 ꢁ CH2), 24.5 (2 ꢁ CH2), 22.6 (CH2),
14.0 (CH3) ppm.
3,5-Dichloro-6-R-[1,4]oxazin-2-ones (Compounds 7a–c)[9,10]
General Procedure
The corresponding cyanohydrins 8a–c (0.14 mol) in chlorobenzene
(90 ml) were added dropwise to a solution of oxalyl chloride (0.582 mol)
in chlorobenzene (400 ml) in a water ice bath at 0 ꢀC. After 30 min,
Et3N ꢂ HCl (0.05 mol) was added, and the reaction mixture was stirred
at 90 ꢀC for 3 h under an inert atmosphere. Then, the solvent and excess
oxalylchloride were evaporated under reduced pressure to afford a yellow-
green oil containing excess of Et3NꢂHCl as white needles. The oil was
poured in ether (400 ml), and the salt was filtered out. The solution
was concentrated under reduced pressure, and the slurry obtained was

934
N. P. Chandia et al.
purified by flash-column chromatography (silica gel) using EtOAc–
heptane (8:2) as the eluent and subsequently crystallized from hexane
overnight. The solvent was eliminated, and the oxazinones were dried
under high vacuum.
3,5-Dichloro-6-methyl-[1,4]oxazin-2-one 7a
Yield: 81%; solid; mp: 70–71 ꢀC; dH [300 MHz, CDCl3]: 2.39 (s, 3H) ppm;
dc [100 MHz, CDCl3]: 150.7 (C3), 150.1 (C2), 142.2 (C6), 123.8 (C5), 17.3
(CH3) ppm. C5H3Cl2NO2 calculated: C, 33.37; H, 1.68; Cl, 39.39; N, 7.78;
O, 17.78%. Found: C, 33.29; H, 2.23; N, 7.50%. HRMS: C5H3Cl2NO2
calculated: 178.9541. Found: 178.9545; EIMS m=z (M+): 180.
3,5-Dichloro-6-propyl-[1,4]oxazin-2-one 7b
Yield: 91%; oil; dH [300 MHz, CDCl3]: 2.63 (m, 2H), 1.75 (m, 2H), 1.01 (t,
3H, J ¼ 7.3 Hz) ppm; dc [100 MHz, CDCl3]: 153.0 (C3), 150.4 (C2), 141.6
(C6), 123.2 (C5), 32.1 (CH2), 19.8 (CH2), 13.1 (CH3) ppm. dc C7H7Cl2NO2
calculated: C, 40.41; H, 3.39; Cl, 34.08; N, 6.73; O, 15.38%. Found: C,
38.58; H, 5.75; N, 7.19%. HRMS: C7H7Cl2NO2 calculated: 206.9854.
Found: 206.9860. EIMS m=z (Mþ): 208.
3,5-Dichloro-6-undecyl-[1,4]oxazin-2-one 7c
Yield: 9%; oil; dH [300 MHz, CDCl3]: 2.62 (m, 2H), 1.68 (m, 2H), 1.24 (s,
16H), 0.88 (t, 3H, J ¼ 6.9 Hz) ppm; dc [100 MHz, CDCl3]: 153.2 (C3),
150.3 (C2), 141.5 (C6), 123.0 (C5), 31.8 (CH2), 30.4 (CH2), 29.5 (CH2),
29.3 (CH2), 28.9 (CH2), 26.3 (CH2), 22.6 (CH2), 14.0 (CH3) ppm.
C15H23Cl2NO2 calculated: C, 56.26; H, 7.24; Cl, 22.14, N, 4.37; O,
9.99%. Found: C, 61.63; H, 8.51; N, 3.72%. HRMS: C15H23Cl2NO2,
calculated: 319.1105. Found: 319.1108. EIMS m=z (Mþ): 320.
5-Chloro-3-iodo-6-R-[1,4]oxazin-2-ones (Compounds 9a–c)
General Procedure
The corresponding dichloro-oxazinones 7a–c (0.028 mol), NaI (0.084
mol), and CSA (10%) were stirred in acetone (10 mL) at room tempera-
ture. A viscous mixture was formed instantaneously, and more acetone
(10 mL) was added to allow homogenization. The suspension was stirred
for 1 h. The mixture was extracted with EtOAc and washed with aqueous

5,50-Dialkyl-6,60-dichloro-2,20-bipyridines
935
Na2S2O3. The organic layer was dried over MgSO4, and the solvent was
removed under reduced pressure. The samples were dried under high
vacuum.
5-Chloro-3-iodo-6-methyl-[1,4]oxazin-2-one 9a
Yield: 73%; solid; dH [300 MHz, CDCl3]: 2.39 (s, 3H) ppm; dc [100 MHz,
CDCl3]: 150.9 (C3), 150.0 (C2), 125.5 (C6), 115.0 (C5), 17.2 (CH3) ppm.
C5H3ClINO2 calculated: C, 22.12; H, 1.11; Cl, 13.06; N, 5.16; O,
11.79%. Found: C, 21.81; H, 2.55, N, 4.79%. HRMS: C5H3ClINO2
calculated: 270.8897. Found: 270.8931. EIMS m=z (M+): 272.
5-Chloro-3-iodo-6-propyl-[1,4]oxazin-2-one 9b
Yield: 78%; oil; dH [300 MHz, CDCl3]: 2.50 (m, 2H), 1.68 (m, 2H), 0.94 (t,
3H, J ¼ 7.2 Hz) ppm; dc [100 MHz, CDCl3]: 153.0 (C3), 150.7 (C2), 125.1
(C6), 114.6 (C5), 32.1 (CH2), 19.5 (CH2), 13.5 (CH3) ppm. C7H7ClINO2
calculated: C, 28.07; H, 2.36; Cl, 11.84; N, 4.68; O, 10.68%. Found: C,
38.51; H, 5.68, N, 6.77%. HRMS: C7H7ClINO2 calculated: 298.9210.
Found: 298.9211. EIMS m=z (Mþ): 300.
5-Chloro-3-iodo-6-undecyl-[1,4]oxazin-2-one 9c
Yield: 80%; oil; dH [300 MHz, CDCl3]: 2.62 (m, 2H), 1.68 (m, 2H), 1.24 (s,
16H), 0.88 (t, 3H, J ¼ 6.9 Hz) ppm; dc [100 MHz, CDCl3]: 153.2 (C3),
150.3 (C2), 141.5 (C6), 123.0 (C5), 31.8 (CH2), 30.4 (CH2), 29.5 (CH2),
29.3 (CH2), 28.9 (CH2), 26.3 (CH2), 22.6 (CH2), 14.0 (CH3) ppm.
C15H23ClINO2 calculated: C, 43.76; H, 5.63; Cl, 8.61, N, 3.40; O,
7.77%. Found: C, 49.75; H, 7.57; N, 2.93%; HRMS: C15H23ClINO2
calculated: 411.0462. Found : 411.0468.
2-Chloro-6-iodo-3-R-pyridine (Compounds 4a–c)
General Procedure
A mixture of the corresponding chloro-iodooxazinones 9a–c (14.73
mmol) and 3 equivalents of 2,5-norboradiene (6 ml) in dry toluene
(50 ml) was warmed for 36, 16, and 13 h for R ¼ methyl, propyl, and
undecyl, respectively. The reaction was carried out in a steel bomb at
140 ꢀC under an argon atmosphere. After the reaction was completed,

936
N. P. Chandia et al.
the crude mixture was diluted with CH2Cl2, and the solvent was evapo-
rated under reduced pressure to afford a dark oil. This oil was subjected
to column chromatography (silica gel, 100% heptane ! 50% heptane=50%
CH2Cl2) to furnish the pyridines.
2-Chloro-6-iodo-3-methyl-pyridine 4a
Yield: 56%; solid; mp: 60.6 ꢀC; dH [300 MHz, CDCl3]: 7.57 (d, 1H, J ¼ 7.5
Hz), 7.20 (d, 1H, J ¼ 7.5 Hz), 2.32 (s, 3H) ppm. dc [100 MHz, CDCl3]:
150.9 (C2), 140.6 (C4), 133.7 (C3), 132.2 (C5), 111.4 (C6), 19.2 (CH3)
ppm. C6H5ClIN calculated: C, 28.43; H, 1.99; Cl, 13.99; N, 5.53%.
Found.: C, 28.44; H, 2.36; N, 5.53%. HRMS: C6H5ClIN calculated:
252.9155. Found: 252.9162. EIMS m=z (Mþ): 253.
2-Chloro-6-iodo-3-propyl-pyridine 4b
Yield: 51%; solid; mp: 45.8 ꢀC; dH [300 MHz, CDCl3]: 7.60 (d, 1H, J ¼ 7.9
Hz), 7.19 (d, 1H, J ¼ 7.7 Hz), 2.63 (t, 2H, J ¼ 7.7 Hz), 1.68 (m, 2H), 0.98
(t, 3H, J ¼ 7.2) ppm; dc [100 MHz, CDCl3]: 150.4 (C2), 139.9 (C4), 136.0
(C3), 133.6 (C5), 111.4 (C6), 34.4 (CH2), 22.1 (CH2), 13.6 (CH3) ppm.
C8H9ClIN calculated: C, 34.13; H, 3.22; Cl, 12.59; I, 45.08; N, 4.98%.
Found: C, 34.33; H, 3.25; N, 4.97%; HRMS: C8H9ClIN calculated:
280.9468. Found: 280.9474. EIMS m=z (M+): 282.
2-Chloro-6-iodo-3-undecyl-pyridine 4c
Yield: 39%; oil; dH [300 MHz, CDCl3]: 7.59 (d, 1H, J ¼ 7.5 Hz), 7.18 (d,
1H, J ¼ 7.8 Hz), 2.64 (t, 2H), 1.70–1.50 (m, 2H), 1.50–1.20 (m, 16H), 0.88
(t, 3H) ppm; dc [100 MHz, CDCl3]: 150.5 (C2), 139.9 (C4), 136.5 (C3),
133.8 (C5), 111.5 (C6), 32.7 (CH2), 32.0 (CH2), 29.7 (CH2 ꢁ 2), 29.6
(CH2), 29.4 (CH2 ꢁ 2), 29.3 (CH2), 29.0 (CH2), 22.8 (CH2), 14.2 (CH3)
ppm. C16H25ClIN calculated: C, 48.81; H, 6.40; Cl, 9.00; I, 32.23, N,
3.56%. Found: C, 49.84; H, 6.65; Cl, N, 3.85%. HRMS: C16H25ClIN
calculated: 393.0720. Found: 393.0719. EIMS m=z (Mþ): 394.
6,60-Dichloro-5,50-dimethyl-[2,20]bipyridine (Compounds 1a–c)[15]
General Procedure
Palladium acetate (0.0254 mmol) was added to a suspension of the corre-
sponding pyridines 4a–c (0.508 mmol), Bu4NBr (0.254 mmol), and

5,50-Dialkyl-6,60-dichloro-2,20-bipyridines
937
K2CO3 (0.508 mmol) in a mixture of DMF=H2O (4 ml=0.04 ml). After
10 min, isopropanol (0.06 ml) was added to the reaction. The mixture
was stirred under an inert atmosphere for 30 h at 115 ꢀC. After cooling
to room temperature, water and dichloromethane were added. The
organic phase was washed with water and dried over MgSO4. The solvent
was evaporated under vacuum. The crude mixture was then diluted with
CH2Cl2 and passed through a short plug of silica, which was repeatedly
washed with CH2Cl2. The washings were combined, and the solvent was
removed in vacuo to obtain the crude product, which was further purified
by column chromatography (silica gel, 50% heptane=dichloromethane) to
furnish pure samples of substituted bipyridines.
6,60-Dichloro-5,50-dimethyl-[2,20]bipyridine 1a
Yield: 84%; solid; mp: 213.5 ꢀC; dH [300 MHz, CDCl3]: 8.23 (d, 2H,
J ¼ 7.7 Hz), 7.65 (d, 2H, J ¼ 7.7 Hz), 2.43 (s, 6H) ppm; dc [100 MHz,
CDCl3]: 153.1 (C6), 151.0 (C2), 140.3 (C4), 132.9 (C5), 119.8 (C3), 19.7
(CH3) ppm. C12H10Cl2N2 calculated: C, 56.94; H, 3.98; Cl, 28.01; N,
11.07%. Found: C, 57.02; H, 4.12; N, 10.83%; HRMS: C12H10Cl2N2
calculated: 252.0221. Found: 252.0213. EIMS m=z (Mþ): 252.
6,60-Dichloro-5,50-dipropyl-[2,20]bipyridine 1b
Yield: 59%; solid; mp 110–113 ꢀC; dH [300 MHz, CDCl3]: 8.25 (d, 2H,
J ¼ 7.9 Hz), 7.64 (d, 2H, J ¼ 7.7 Hz), 2.74 (t, 4H), 1.72 (m, 4H), 1.00
(t, 6H) ppm; dc [100 MHz, CDCl3]: 152.9 (C6), 150.6 (C2), 139.5 (C4),
136.7 (C5), 119.7 (C3), 35.0 (CH2), 22.3 (CH2), 13.7 (CH3) ppm.
C16H18Cl2N2 calculated: C, 62.14; H, 5.87; Cl, 22.93; N, 9.06%. Found:
C, 63.87; H, 6.51; N, 7.60%. HRMS: C16H18Cl2N2 calculated:
308.0847. Found: 308.0856. EIMS m=z (Mþ) 309.
6,60-Dichloro-5,50-diundecyl-[2,20]bipyridine 1c
Yield: 54%; dH [300 MHz, CDCl3]: 8.25 (d, 2H, J ¼ 8.1 Hz), 7.64 (d, 2H,
J ¼ 7.2 Hz), 2.75 (t, 4H), 1.75–1.50 (m, 4H), 1.50–1.10 (m, 32H), 0.88
(t, 6H) ppm; dc [100 MHz, CDCl3]: 152.9 (C6), 150.7 (C2), 139.6 (C4),
137.2 (C5), 119.9 (C3), 33.2 (CH2), 32.0 (CH2), 29.7 (CH2 ꢁ 2), 29.7
(CH2), 29.4 (CH2 ꢁ 2), 29.3 (CH2), 22.8 (CH2), 14.2 (CH3) ppm.
C32H50Cl2N2 calculated: C, 72.02; H, 9.44; Cl, 13.29, N, 5.25%, solid.
Found: C, 72.89; H, 11.16; N, 2.17%. HRMS: C32H50Cl2N2 calculated:
532.3351. Found: 532.3340. EIMS m=z (Mþ): 533.

938
N. P. Chandia et al.
ACKNOWLEDGMENT
This work was supported by the F. W. O. Vlaanderen, the University of
Leuven, and a bilateral Flemish–Chilean grant, BOF-BIL03=02. S. V.
thanks the Institute for the Promotion of Innovation through Science
and Technology in Flanders (Belgium, I. W. T.), and W. M. D. B. (Post-
doctoral Fellow of the Research Foundation, Flanders [F. W. O.
Vlaanderen] thanks the F. W. O. Vlaanderen for the fellowship received
and for a Krediet aan Navorsers.
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