LDA的制备(标准).pdfVIP

Organic Syntheses, Coll. Vol. 10, p.107; Vol. 78, p.82 EFFICIENT SYNTHESIS OF HALOMETHYL-2,2-BIPYRIDINES: 4,4-BIS(CHLOROMETHYL)-2,2-BIPYRIDINE [ 2,2-Bipyridine, 4,4-bis(chloromethyl)- ] 1 Submitted by Adam P. Smith, Jaydeep J. S. Lamba, and Cassandra L. Fraser . Checked by Motoki Yamane and Koichi Narasaka. 1. Procedure A. 4,4-Bis[(trimethylsilyl)methyl]-2,2-bipyridine . A 500-mL, two-necked, round-bottomed flask (Note 1), equipped with a nitrogen inlet, magnetic stirrer, and rubber septum is charged with tetrahydrofuran (THF) (90 mL) (Note 2) and diisopropylamine (9.8 mL, 69.7 mmol) (Note 3). The reaction mixture is cooled to −78°C and a solution of butyllithium (n-BuLi) (1.7 M in hexanes, 36.0 mL, 61.4 mmol) (Note 4) is added. The solution is stirred at −78°C for 10 min, warmed to 0°C and stirred for 10 min, then cooled back to −78°C. A solution of 4,4-dimethyl-2,2-bipyridine (5.14 g, 27.9 mmol) (Note 5) in THF (130 mL) (Note 2), prepared in a 250-mL, two-necked, round-bottomed flask under a nitrogen atmosphere, is added via cannula to the cold lithium diisopropylamide (LDA) solution. The resulting maroon-black reaction mixture is stirred at −78°C for 1 hr, then chlorotrimethylsilane (TMSCl) (8.85 mL, 69.7 mmol) (Note 6) is rapidly added via syringe. After the solution becomes pale blue-green (≈10 sec after the TMSCl addition), the reaction is quenched by rapid addition of absolute ethanol (10 mL). (Note: the reaction should be quenched regardless of color change after a maximum of 15 seconds to avoid over silylation). The cold reaction mixture is poured into a separatory funnel (1 L) containing aqueous saturated sodium