A Convenient Access to Biquinoline Carbaldehydes using Nickel-Phosphine Complex-Mediated Homocoupling of Haloquinoline Carbaldehydes in One-Pot Reaction

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.


Introduction
There is growing interest in the chemistry of biquinoline compounds due to the possibility of their use in high performance heterocyclic ladder polymers 1 , as ligands for the preparation of metal complexes bearing biological activities, such as antibacterial, antifungal, antimalarial and antitumor properties and as hydrogenation catalysts [2][3][4] .Even though there are several synthetic methods of biquinoline derivatives cited in the literature 5 , 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 sources 6,7 .
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 water 6 , we protected the aldehyde function using ethylene glycol in the presence of montmorillonite (K10) 9 .The amount of zinc dust was added in portions to a solution of PPh 3 and NiCl 2 .6H 2 O in DMF at 70 °C under argon followed by the addition of the protected 2-chloroquinoline carbaldehyde 2 (Scheme 1).
Experimental 1 H NMR spectra were recorded on a BRUKER AC spectrometer (200 or 300 MHz) using CDCl 3 .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 HCN 10 .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-Cohn 11 (Scheme 2).

N H O
Scheme 2

Results and Discussion
We would like to disclose here our preliminary results using the in situ generated Ni(0) complex, [(PPh 3 )] 4 Ni, 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 [(PPh 3 )] 4 Ni° was conducted by the Zn(0) reduction of NiCl 2 .6H 2 O in the presence of PPh 3 .

Figure 1 .
Figure 1.The crystal structure of 3d