4-(1-Piperazinyl)benzonitrile

White to yellow solid

4-Cyanochlorobenzene (13.8 g, 100 mmol) and piperazine (12.9 g, 150 mmol) were dissolved in a mixture of 120 ml of toluene and 80 ml of tetrahydrofuran, and degassed at room temperature by passing nitrogen through for 15 min. Dry sodium tert-butoxide (13.5 g, 140 mmol) was added and the mixture was degassed for a further 10 min. In a separate vessel, [2-(2, 4, 6-triisopropylphenyl)phenyl]dicyclohexylphosphine (95 mg, 0.2 mmol) and (dibenzylideneacetone)palladium (40 mg, 0.05 mmol) were stirred under nitrogen in 10 ml of degassed tetrahydrofuran. After 30 min, this catalyst solution was introduced dropwise at room temperature into the larger flask with the aid of a transfer needle. On completion of addition, the reaction was heated to internal temperature 90° C. After 8 h, the reaction was allowed to cool to 50° C. and the precipitated solid was filtered off. The filtrate was extracted with dilute hydrochloric acid at pH 3. The aqueous phase was removed and adjusted to pH 10 with the aid of sodium hydroxide solution. The precipitated white solid was filtered off and dried under reduced pressure. 17.8 g (95 mmol, 95percent of theory) of N-(4-cyanophenyl)piperazine were obtained. The product content of the solid was determined to be >99percent by quantitative proton NMR.A mixture of 4-fluorobenzonitrile (3, 0.36 g, 3 mmol), piperazine (0.64 g, 7.4 mmol) and Ka) Under a nitrogen atmosphere, a stirred miture of 10.0 grams (0.055 mole) of 4-bromobenzonitrile (available from Aldritch Chemical Company) and 23.7 grams (0.28 mole) of piperazine (available from Aldritch Chemical Company was heated at 120°C for about 45 hours. After this time, the reaction mixture was taken up in 150 ml of aqueous 10percent sodium hydroxide. The resulting solution was extracted with three 50 mL portions of methylene chloride. The combined extracts were washed with one 50 mL portion of an aqueous saturated sodium chloride solution, dried with sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, yielding 8.6 grams of a green paste. The green paste was purified by column chromatography on silica gel, yielding 3.8 grams of a paste. The paste was taken up in 50 mL of diethyl ether. The resulting solution was warmed on a rotovap and decanted away from the insoluble paste. The decantate was concentrated, yielding 3.2 grams of the title comound. The NMR spectrum was consistent with the proposed structure.

Molecular Weight:187.24
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:187.110947427
Monoisotopic Mass:187.110947427
Topological Polar Surface Area:39.1
Heavy Atom Count:14
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes