Nickel chloride/Zinc/Pyridine

REDUCTION, REAGENTS Bis(N-methylpi-perazinyl)aluminum hydride. Borane-Di-methyl sulfide. Borane-Tetrahydrofurane. Borane-Pyridine. n-Butyllithium-Diisobu-tylaluminum hydride. Calcium-Amines. Diisobutylaluminum hydride. 8-Hydroxy-quinolinedihydroboronite. Lithium aluminum hydride. Lithium 9-boratabicy-clo[3.3.1]nonane. Lithium n-butyldiisopro-pylaluminum hydride. Lithium tri-j c-butylborohydride. Lithium triethylborohy-dride. Monochloroalane. Nickel boride. 2-Phenylbenzothiazoline. Potassium 9-(2,3-dimethyl-2-butoxy)-9-boratabicy-clo[3.3.1]nonane. Raney nickel. Sodium bis(2-methoxyethoxy)aluminum hydride. Sodium borohydride. Sodium borohy-dride-Nickel chloride. Sodium borohy-dride-Praeseodymium chloride. So-dium(dimethylamino)borohydride. Sodium hydrogen telluride. Thexyl chloroborane-Dimethyl sulfide. Tri-n-butylphosphine-Diphenyl disulfide. Tri-n-butyltin hydride. Zinc-l,2-Dibromoethane. Zinc borohydride. 

The Ni(0)-mediated coupling reaction could be successfully applied to Vitamin D derivatives. Nickel chloride is reduced with zinc powder in pyridine to nickel(O), and this forms a brick-red complex with the acrylate ester. This, in turn, is smoothly alkylated by the alkyl iodide. The reaction is widely appUcable it can also be carried out successfully with the sulfur dioxide adducts, and ethyl acrylate may be replaced by methyl vinyl ketone as well. 

Nickel chloride I zinc I pyridine Nickel-catalyzed 1,4-addition to acrylic acid esters... 

In Volume V of this series, syntheses were presented for coordination compounds of 2,2 -iminodipyridine [di-2-pyridylamine, NH(C6H4N)2] with copper(II) and cobalt-(II). Nickel(II) has also been shown to coordinate with this ligand. A similar behavior is exhibited by zinc salts, which form 1 1 derivatives if a 1 1 mol ratio of reactants is used. The specific choice of a solvent medium for synthesis is dictated by the solubility of the zinc compound. Either acetone or methanol may be used with zinc chloride, methanol with zinc acetate, and pyridine with zinc cyanide. 

Selective reduction of either the pyridine or the benzene rings in quinolines and isoquinoline can be achieved the heterocyclic ring is reduced to the tetrahydro level by sodium cyanoborohydride in acid solution,by sodium borohydride in the presence of nickel(II) chloride, by zinc borohydride," or, traditionally, by room temperature and room pressure catalytic hydrogenation in methanol. However, in strong acid solution it is the benzene ring which is selectively saturated " longer reaction times can then lead to decahydro-derivatives. 

The solution to this synthesis problem goes back to the work of Reiner Sust-mann, who successfully carried out the formal, nickel(0)-mediated addition of alkyl or aryd halides to electron-deficient alkenes, like acrylate esters or acrylonitrile. [101] Sub-stoichiometric amounts of nickel(ll) chloride hexahydrate (15-20 mole %) are reduced with zinc in presence of pyridine to nickel(O), which forms together with pyridine a complex with the alkene. Oxidative addition of the alkyl halide leads to an alkyl-nickel species, the carbon-metal bond of which undergoes an alkene insertion. Hydrolysis gives ultimately the product. Heck reaction products are not observed. 

Into a 1-1 four necked flask, dry pyridine (500 ml), 4-bromotoluene (113, 44.30 g, 0.259 mol), 2-chlorobenzonitrile (114, 35.60 g, 0.259 mol), anhydrous nickel(II) chloride (3.24 g, 0.025 mol, 10 mol%), triphenylphosphine (PPh3, 13.10 g, 0.05 mol, 2 eq. to Ni) and zinc-powder (67.60 g, 1.034 mol, 4 eq.) were charged under a nitrogen atmosphere and stirred at room temperature for 30 minutes (formation of Ni(0) catalyst). The temperature was raised to 80 C and the mixture was stirred for additional 6 hours. Then, toluene (400 ml) was added, and the solid filtered off while it was still hot. The solvents were recovered under reduced pressure. Then, toluene (500 ml) was added to the residue, and the solid was filtered off while it was still hot and washed with hot toluene (100 ml). The warm toluene layer was washed with 5% aqueous hydrochloric acid (300 ml), then with 5% aqueous sodium hydrogencarbonate solution (300 ml) and then with warm water (2x300 ml). The toluene layer was concentrated to obtain 28.4 g (57%) of pure (ca. 97%, HPLC) 4 -methyl-2-cyanobiphenyl (112) as a white crystalline substance, m.p. 49-50 "C (cyclohexane). 

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