Heterogenous catalytic method for the synthesis of biquinolines and bipyridines

Article abstract of DOI:10.1007/s10593-009-0208-8

A method has been developed for the synthesis of 2,2′- and 3,3′-biquinolines and of 4,4′-bipyridine based on the coupling of 2- and 3-bromoquinoline or 4-bromopyridine using a Pd/C-hydrazine-KOH catalytic system.

Full text of DOI:10.1007/s10593-009-0208-8

Chemistry of Heterocyclic Compounds, Vol. 44, No. 12, 2008
HETEROGENOUS CATALYTIC METHOD
FOR THE SYNTHESIS OF BIQUINOLINES
AND BIPYRIDINES
A. V. Aksenov1 and V. I. Goncharov2
A method has been developed for the synthesis of 2,2'- and 3,3'-biquinolines and of 4,4'-bipyridine
based on the coupling of 2- and 3-bromoquinoline or 4-bromopyridine using a Pd/C-hydrazine-KOH
catalytic system.
Keywords: 2,2'-biquinoline, 3,3'-biquinoline, 4,4'-bipyridine, 4-bromopyridine, 2-bromoquinoline,
3-bromoquinoline, palladium on carbon, coupling.
A series of methods for the synthesis of 3,3'-biquinoline (2) is known [1-4]. These methods are based on
the cross coupling of 3-bromoquinoline (1) under the action of different metals but have a number of
deficiencies. The method [1] using equimolar amounts of 3-bromoquinoline and catalyst employs the expensive
metallic palladium. Despite the fact that in method [2] a catalytic amount of metallic palladium is involved it
cannot be used repeatedly. The deficiencies of methods [3] and [4] using a catalytic system based on Ni(0) are
the need for chromatographic separation of the reaction mixture which impedes work up of large quantities of
the 3,3'-biquinoline. Hence we decided to develop a more efficient synthesis of compound 2.
Br
catalyst
N
N
N
1
2
We have attempted to develop a method allowing a repeated use of the palladium catalyst based on the
work in [1]. It was found that 10% Pd/C can be used in place of palladium black. It can be regenerated using the
system hydrazine–KOH. The yield is virtually unchanged at 46%.
It was further shown that the catalyst can be regenerated in the course of the reaction by gradual addition
to the reaction mixture of a solution of alkali in hydrazine hydrate. This permits use of a catalytic amount of
palladium and repeated use of the catalyst. However, the yield in this case decreases to 28%.
__________________________________________________________________________________________
2
1Stavropol State University, Stavropol 355009, Russia; e-mail: k-biochem-org@stavsu.ru. Stavropol
State Medicinal Academy, Stavropol 355017, Russia; e-mail: sgma@statel.stavropol.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1839-1840, December, 2008. Original article submitted
October 9, 2007.
0009-3122/08/4412-1491©2008 Springer Science+Business Media, Inc.
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Pd/C
N
N2H4, KOH
N
N
Br
3
4
Br
Pd/C
N
N
N2H4, KOH
N
6
5
This method can be used in the synthesis of other biquinolines and bipyridines, e.g. 2,2'-biquinoline (4)
ad 4,4'-bipyridine (6).
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker WP-200 (200 MHz) instrument using TMS as internal
standard. Monitoring of the reaction course and purity of the synthesized compounds was carried out on Silufol
UV-254 plates with ethyl acetate as solvent.
General Method. A solution of KOH (0.67 g, 12 mmol) and 88% hydrazine hydrate (1.14 g, 20 mmol)
in ethyl alcohol (3 ml) was added dropwise over 2 h to a mixture of the corresponding halo derivative (10 mmol)
and Pd/C (0.51 g, 0.5 mmol) in refluxing ethanol (10 ml). Solvent was evaporated and the residue was
recrystallized from DMF, separating the catalyst and KBr on a plaited filter. The catalyst was washed with
water, dried, and used repeatedly.
1
3,3'-Biquinoline (2). Yield 0.72 g (28%) with mp 269-271ºC (alcohol) (mp 217ºC [1]). H NMR
spectrum, δ, ppm (J, Hz): 7.63 (2H, ddd, J5,6 = 8.1, J6,7 = 6.9, J6,8 = 1.2, H-6,6'); 7.77 (2H, ddd, J6,7 = 6.9,
J7,8 = 8.4, J5,7 = 1.5, H-7,7'); 7.94 (2H, dd, J5,6 = 8.1, J5,7 = 1.5, H-5,5'); 8.18 (2H, dd, J7,8 = 8.4, J6,8 = 1.2,
H-8,8'); 8.46 (2H, d, J2,4 = 2.4, H-4,4'); 9.29 (2H, d, J2,4 = 2.4, H-2,2'). Found, %: C 84.71; H 4.58; H 10.71.
C18H12N2. Calculated, %: C 84.37; H 4.69; N 10.94.
2,2'-Biquinoline (4, C18H12N2). Yield 1 g (39%), mp 197-198ºC (alcohol) (mp 196-198ºC [5]). A
sample mixed with a known sample (commercially available) did not give a melting point depression. The
1H NMR spectrum was identical to that given in [5].
4,4'-Bipyridine (6, C10H8N2). Yield 0.53 g (34%) with mp 112-114ºC (water) (mp 112-114ºC [5]). A
1
sample mixed with a known sample (commercially available) did not give a melting point depression. The H
NMR spectrum was identical to that given in [5].
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