A convenient access to biquinoline carbaldehydes using nickel-phosphine complex-mediated homocoupling of haloquinoline carbaldehydes in one-pot reaction

Article abstract of DOI:10.1155/2010/782913

The homocoupling of 2-chloro-carbaldehyde derivatives gave the corresponding 2,2'-biquinolines by using the in situ generated reactive reagent Ni[(PPh₃)]₄. Several new 2-chloro-3-(1.3 dioxalan-2yl) quinoline derivatives are synthesized and structurally characterized. The overall structures of biquinoline derivatives are not planar.

Full text of DOI:10.1155/2010/782913

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2010, 7(4), 1196-1199
http://www.e-journals.net
A Convenient Access to Biquinoline Carbaldehydes using
Nickel-Phosphine Complex-Mediated Homocoupling of
Haloquinoline Carbaldehydes in One-Pot Reaction
AHMED BENAMEUR*, TAOUES BOUMOUD,
BOUDJEMAA BOUMOUD§ and SALAH RHOUATI
Laboratoire des Produits Naturels d’origine Végétale et de Synthèse,
Organique. Département de Chimie. Faculté des Sciences,
Université Mentouri de Constantine 25000 Constantine, Algérie.
ta_boumoud@yahoo.fr
Received 10 October 2009; Revised 10 December 2009; Accepted 4 February 2010
Abstract: The homocoupling of 2-chloro-carbaldehyde derivatives gave the
corresponding 2,2’-biquinolines by using the in situ generated reactive reagent
Ni[(PPh3)]4. Several new 2-chloro-3-(1.3 dioxalan-2yl) quinoline derivatives are
synthesized and structurally characterized. The overall structures of biquinoline
derivatives are not planar.
Keywords: 2-Chloroquinoline carbaldehyde, Homocoupling, One-pot reaction, 2,2’-Biquinoline derivatives.
Introduction
There is growing interest in the chemistry of biquinoline compounds due to the possibility of their
use in high performance heterocyclic ladder polymers1, as ligands for the preparation of metal
complexes bearing biological activities, such as antibacterial, antifungal, antimalarial and
antitumor properties and as hydrogenation catalysts2-4. Even though there are several synthetic
methods of biquinoline derivatives cited in the literature5, most of them suffer from some
drawbacks such as low yields due to the formation of by-products, the use of highly reactive
coupling reagents and competitive reductions from the presence of protonic sources6,7.
To overcome these difficulties, we describe herein an efficient one-pot synthesis of some new
biquinoline carbaldehyde derivatives which consists of the homocoupling of haloquinolines
mediated by nickel-phosphine complexes. This method is based on the procedure described by
Tiecco et al. 8, which uses the in situ generated nickel(0) complex.
To surmount the well known competitive reduction of aldehyde function and
haloheterocycles by Zn(0) in the presence of a proton source such as water6, we protected the
aldehyde function using ethylene glycol in the presence of montmorillonite (K10)9. The amount

1197
Ta. BOUMOUD et al.
of zinc dust was added in portions to a solution of PPh3 and NiCl2.6H2O in DMF at 70 °C under
argon followed by the addition of the protected 2-chloroquinoline carbaldehyde 2 (Scheme 1).
O
O
R1
R2
CHO
ethylene glycol/K10
toluene
Cl
R1
R2
R1
R2
O
NiCl2.6H2O, Zn
PPh3/DMF
O
R2
R1
N
N
O
N
N
Cl
2
1
O
3
Scheme 1
Experimental
1H NMR spectra were recorded on a BRUKER AC spectrometer (200 or 300 MHz) using CDCl3.
Chemical shifts are reported in parts of million (ppm) relative to TMS (0.0) as internal standard
and coupling constant (J) is reported in hertz (Hz). 13C NMR spectra were recorded on a
BRUKER AC spectrometer (75 or 50 MHz). High resolution mass spectral analysis (HR-MS)
were performed by CMPO (the Centre regional de Mesure de Physique de l’Ouest, Rennes,
France) on a ZabSpecTOF (LSIMS, 4KV) and presented as m/e (relative intensity, assignment).
Zinc powder was washed successively with diluted hydrochloride acid, water, ethanol,
acetone and diethyl ether and dried under reduced pressure. Anhydrous DMF was purified to
remove traces of HCN10. All other reagents were commercially available and were purified or
used as such.
The 2-chloroquinoline carbaldehyde derivatives (2), from which the present synthesis is
initiated, were prepared from the corresponding acetanilide using the method reported by Meth-
Cohn11 (Scheme 2).
R1
R1
CHO
Cl
DM F
POCl3
/
75°C 3H
NH
N
R2
O
R2
1
2
Scheme 2
General procedure for the synthesis of biquinoline derivatives
Zinc dust (127 mg, 1.92 mmol) was added in portions to a stirred deep blue solution of
NiCl2.6H2O (428 mg, 1.8 mmol) and triphenylphosphine (1.9 g, 7.2 mmol) in degassed DMF
(20 mL) at 70 °C under argon. The resulting mixture was stirred for 1 h, the time necessary for
Ni(0) formation (red-brown color). 2-Chloro-3-(1.3 dioxalan-2yl) quinoline derivative (1.8 mmol)
dissolved in degassed DMF (10 mL) was added drop wise and the mixture was stirred for a further
3 h. Upon cooling to room temperature, the reaction mixture was poured into a dilute ammonia
solution (5%, 30 mL), the resulting solution was extracted with CH2Cl2/Et2O (3×100 mL, 2/1) and
evaporated. The residue obtained was dissolved in CH2Cl2 (60 mL), washed with water (4×20 mL)
and the combined organic layers were extracted with a saturated solution of NaCl (40 mL), dried
over anhydrous MgSO4 and then concentrated to give the crude product which was purified by
column chromatography on silica gel using ethyl acetate / pentane (1/1) as eluent to afford the
corresponding biquinoline derivative in pure state.
All compounds obtained according to this protocol were characterized and identified by
NMR, mass spectra and elemental analysis. The results are summarised in Table 1.

A Convenient Access to Biquinoline Carbaldehydes
1198
Table 1. Ni[(PPh3)]4 catalyzed synthesis of biquinoline derivatives
Biquinoline 3a
R1
H
R2
H
Yieldb %
53
60
56
65
3a
3b
3c
3d
H
OMe
OMe OMe
Me Me
aThe products were characterized by their mass, H, 13C NMR and elemental analysis Yield based on the
amount of starting compound employed and calculated from the amount of product isolated by column
chromatography.
1
b
Spectral data for all the compounds
[3,3-Bis[1,3]dioxalan-2-yl]-2,2’]biquinoline (3a)
1H NMR (CDCl3): δ (ppm) = 8.60 (s, 2H, H4), 8.17 (s, 2H, H5), 7.96 (d, 2H, H8), 7.79 (d, 2H,
H7), 7.62 (d, 2H, H6), 6.41 (s, 2H, CH), 3.94 (m, 8H, CH2); 13C NMR(CDCl3): ä (ppm) = 157.4,
147.6, 135.4, 131.4, 130.5, 129.7, 128.5, 127.7, 127.5, 101.2, 65.4; HR-MS.FAB+ (m/z) 400.14231
([M+] (calc.: 400.1423). Elemental analysis (%) for C24H20N2O4: C (71.99), H (5.03), N (7.00),
Calc.: C (72.05), H (5.12), N (6.70). Yellow-brown solid.
[3,3-Bis[1,3]dioxalan-2-yl]-7,7’-dimethoxy[2,2’]biquinoline (3b)
1H NMR (CDCl3): δ (ppm) = 8.5 (s, 2H, H4), 7.83 (d, 2H, H5), 7.5 (s, 2H, H8), 7.26 (d, 2H, H6),
6.25 (s, 2H, CH), 4.02 (m, 4H, CH2), 3.96 (s, 6H, OCH3), 3.85 (m, 4H, CH2),; 13C NMR (CDCl3,
75MHz, ppm): δ = 161.6, 152.6, 146.1, 135.1, 129.4, 128.9, 122.9, 120.8, 107.7, 101.3, 65.5, 56.0;
HR.MS.FAB+ (m/z) 460.16344 ([M+] (calc.: 460.1612); Elemental analysis (%) for C26H24N2O6 :
C (67.82), H (5.25), N (6.08), Calc.: C (68.04), H (5.65), N (5.88). White solid.
[3,3-Bis[1,3]dioxalan-2-yl]-6,7,6’,7’-tetramethoxy-[2,2-]biquinoline (3c)
1H NMR (CDCl3): δ (ppm) = 8.43 (s, 2H, H4), 7.50 (s, 2H, H5), 7.18 (s, 2H, H8), 6.19 (s, 2H,
CH), 4.07 (s, 6H, OCH3), 4.04 (s, 6H, OCH3), 3.91 (m, 8H, CH2); 13C NMR(CDCl3): δ (ppm) =
155.2, 153.4, 150.5, 144.8, 133.6, 129.3, 123.35, 108.4, 105.6, 101.4, 65.5, 56.5 ; Elemental
analysis (%) for C28H28N2O8, C (64.61), H (5.42), N (5.38), (calc.: C (64.67), H (5.55), N (5.52);
HR-MS.FAB+ (m/z) 520.18457 ([M+] (calc.: 520.1831). White solid.
[3,3-Bis[1,3]dioxalan-2-yl]-6, 7,6’,7-’tetramethyl-[2,2’] biquinoline (3d)
1H NMR (CDCl3) : δ (ppm) = 8.45 (s, 2H, H4), 7.91 (s, 2H, H8), 7.66 (s, 2H, H5), 6.29 (s, 2H,
CH), 4.19-4.08 (m, 8H, CH2), 2.48 (s, 12H, CH3); 13C NMR (CDCl3): δ (ppm) = 156.6, 146.7,
140.8, 137.3, 134.4, 130.4, 129.1, 127.6, 126.2, 101.4, 65.4, 20.9, 20.5. White shiny crystals.
Furthermore, the crystal structure of 3d was determined (Figure 1).
Figure 1. The crystal structure of 3d

1199
Ta. BOUMOUD et al.
Results and Discussion
We would like to disclose here our preliminary results using the in situ generated Ni(0) complex,
[(PPh3)]4Ni, for the preparation of some 2,2’-biquinoline derivatives (3).
After some exploratory experiments, we determined that the best results to produce 3 were
achieved on adding zinc dust (1.92 mmol)) to a solution of nickel(II) chloride hexahydrate
(1.8 mmol) and triphenyphosphine (7.2 mmol) in degassed dimethylformamide (20 mL) under
argon at 70 °C followed by the addition of 2-chloro-3-(1.3 dioxalan-2yl) quinoline derivative
(1.8 mmol). The method seems to be generally applicable, thus substituted 2-chloro-3-(1.3
dioxalan-2yl) quinoline underwent the homocoupling to afford the corresponding biquinolines
under the above described conditions.
In summary, the present method for the synthesis of 2,2’-biquinoline-carbaldehydes has
overcome some difficulties by using the modified procedure of Tiecco et al.8.
Conclusion
In conclusion, we have synthesized and characterised some new biquinoline carbaldehyde
derivatives by using the modified procedure of Tiecco et al.8 in which a stoichiometric amount of
a nickel coupling reagent was used. The generation of [(PPh3)]4Ni° was conducted by the Zn(0)
reduction of NiCl2.6H2O in the presence of PPh3.
Acknowledgments
We wish to thank the “Ministère de l’Enseignement Supérieur et de la Recherche Scientifique” for
financial support of this work.
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