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Br
Cl
Mg
Br
Mg
Cl
Rx-ID: 23053998 View in Reaxys 1/1 Yield Conditions & References 4-Chlorophenyl-5-[(3,4-isopropylidine)-2-methylpyridine]-methanol hydrochloride; 4b To a refluxing (.similar.70°C) suspension of magnesium metal turning (18.23 g, 1.25 eq) in 500 ml of THF was added 4-bromochlorobenzene (14.45 g, 10percent of total quantity) and a crystal of iodine. After the initiation of the reac‐ tion, the remaining quantity of 4-bromochlorobenzene (130.05 g in 200 ml of THF) was added over a period of 60 minutes at reflux temperature. 30 minutes after the complete addition, 125 g of 3,4-isopropylidine pyridoxal 3a (in 200 ml of THF) was added at .similar.70°C [THF reflux temperature] to the reaction mixture (Grignard reagent pre‐ pared) over .similar.45 minutes. After the addition, refluxing was continued for 2 hours. Then THF was distilled off under reduced pressure [.similar.600 mm of Hg, recovery of THF .similar.50-60percent (v/v)] to get a thick residue. The residue obtained was cooled to .similar.40°C and was then quenched with 1 M HCl (1300 ml). The mixture was then cooled to 5-10°C for 30 minutes when 4-chlorophenyl-5-[(3,4-isopropylidine)-2-methylpyridine]-methanol hydro‐ chloride 4b precipitated as off-white granules. The product was isolated by filtration and was then washed with di‐ chloromethane (2 x 260 ml). This was then dried at 70°C under reduced pressure (.similar.250 mm of Hg) till con‐ stant weight. The yield was 85percent (183 g). M.P: 189-193°C.1H-NMR (DMSO-d6): 1.46 ppm (3H, s, O-C(CH3)O); 1.51 ppm (3H, s, O-C(CH3)-O); 2.53 ppm (3H, s, Ar-CH3); 4.84 ppm (2H, q, J= 17Hz, -CH2-O-); 5.95 ppm (1H, bs, Ar-CH-O-); 7.39 ppm [2H, d, J= 8.4Hz, Ar-H (chlorophenyl ring)]; 7.45 [2H, d, J= 8.2Hz , Ar-H (chlorophenyl ring)]; 8.25 ppm [1H, s, Ar-H (pyridine ring)]. Mass Spec: (319), 262, 243, 226, 149, 139, and 77 With iodine in tetrahydrofuran, Time= 1.5h, T= 70 °C , Heating / reflux Patent; Generics (UK) Limited; EP1398316; (2004); (A2) English View in Reaxys 3 :Preparation Example 3 0.24 g (10 mmol) of magnesium and 10 mL of anhydrous THF were weighed in a roundbottom flask, and a small amount of iodine was put thereinto, and the system was stirred at room temperature for 30 minutes to activate magnesium. 1.8 g (10 mmol) of 4-chlorobenzene bromide was added at room temperature there‐ to, and the contents were stirred at room temperature for 2 hours. The obtained anhydrous THF solution of 4-chloro‐ phenylmagnesium bromide was titrated using 1,10-phenanthroline, and its concentration was found to be 0.80 mol/L. in tetrahydrofuran, Time= 2h, T= 20 °C Patent; Mitsui Chemicals, Inc.; Agency for Science, Technology and Research; EP2412694; (2012); (A1) Eng‐ lish View in Reaxys in tetrahydrofuran, Inert atmosphere Murai, Masahito; Hosokawa, Naoki; Roy, David; Takai, Kazuhiko; Organic Letters; vol. 16; nb. 16; (2014); p. 4134 - 4137 View in Reaxys With iodine in tetrahydrofuran, T= 20 °C Yang, Wanfei; Chen, Huoji; Li, Jianxiao; Li, Chunsheng; Wu, Wanqing; Jiang, Huanfeng; Chemical Communi‐ cations; vol. 51; nb. 46; (2015); p. 9575 - 9578 View in Reaxys Bis-(Aryl)manganese Reagents 5a–i; General Procedure 2 (GP2) General procedure: A dry and argon-flushed Schlenk tube, equipped with a magnetic stirring bar and a rubber sep‐ tum, was charged with LiCl (0.42 g, 10.0 mmol, 1.20 equiv) and heated at 450 °C under high vacuum for 5 min. After cooling to r.t. under vigorous stirring, Mg turnings (0.47 g, 19.2 mmol, 2.40 equiv) and freshly distilled THF (8 mL) were added. The mixture was cooled to 0 °C, the corresponding aryl bromide (8.00 mmol, 1.00 equiv) was added and the reaction mixture was allowed to warm to r.t. The completion of the metalation was monitored by GC analysis of hydrolyzed and iodolyzed aliquots. When the oxidative insertion was complete, the solution was transferred to an‐ other predried and argon-flushed Schlenk tube, before titrating against I2. The remaining arylmagnesium halide was cooled to 0 °C and transmetalated with a solution of MnCl2·2LiCl (0.55 equiv, 1.0 M in THF). The resulting bis-(ar‐ yl)manganese reagent was titrated with an iodine solution one more time before use. With lithium chloride in tetrahydrofuran, Time= 0.5h, T= 0 - 25 °C , Inert atmosphere, Schlenk technique