BBr3裂解醚反应
BBr3是⼀种温和、优良的醚的去甲基化试剂，并且不影响分⼦中的酯基和双键，在许多天然产物的全合成中常使⽤它。⼀般使⽤CH2Cl2, benzene, pentane作为溶剂，在-78 ℃到室温下进⾏。有⼀点需注意，当底物分⼦中杂原⼦数多时，应增加BBr3量。使⽤BBr3有⼀个最⼤的缺点是BBr3对空⽓敏感，使⽤时会冒出⼤量⽓雾；并在加⽔后处理时常出现⼤量的络合物，此时最好使⽤其它的⽅法，否则后处理艰难并导致收率下降。BI3, BCl3的使⽤如同BBr3。
反应实例
⼀、三溴化硼
Table 1.Cleavage of Ethers by Boron Tribromide
Ether Alcohol Yield (%)Bromide Yield (%)
Et2O EtOH61EtBr86
i-Pr2O i-PrOH50i-PrBr80
downpaymentn-Bu2O n-BuOH62n-BuBr77
coil spring
Ph-O-Pr-i PhOH64i-PrBr62
乌鲁木齐教育
Ph-O-Bu-n PhOH75n-BuBr76
2-溴苯甲醚2-溴苯酚81----
2,4,6-三甲基苯甲醚2,4,6-三甲基苯酚87----
待遇英文PhCH2-O-Pr-n n-PrOH71PhCH2Br75
General Procedure forCleavage of Ether with BBr3. Aweighed quantity of the ether (usually 15 to 20 g) is introduced into the reactionflask and cooled in an ice-bath. The calculated quantity of boron tribromide is slowly introduced through a dropping funnel. In all cas boron tribromide andether are allowed to react in the ratio of 1 mol of boron tribromide to 3 mol of ether. After addition of boron tribromide, the reaction mixture is heated ona water bath for 40 min. The alkyl bromide is distilled directly from thereaction mixture. After removal of the alkyl bromide by distillation, theresidure remaining in the flask is hydrolyzed with a minimum amount of 10% sodium hydroxide solution. The resulting solution is acidified withhydrochloric acid and extracted with ether.
【F. L. Benton and T. E. Dillon, J. Am. Chem. Soc.1942,64, 1128】
⼆、BX3和Me2S的络合物
启德教育其为BBr3的改良⽅法。BBr3或BCl3和Me2S的络合物是固体物，容易制备并在惰性⽓体中能长期保存。⼀般使⽤2到4倍量即可。
负责人英语Table2.Cleavage of Ethers with BBr3.S(CH2)2 Complex
a) Reaction run at 83°C. b) GLC yield. C) Isoated yield.油压开关
General Procedure for the Cleavage ofEthers with Boron Trihalide-Methyl sulfide Complex. To a flame-dried 100 mLflask under an atmosphere of nitrogen is added 1,2-dichloroethane (30 mL) andan amount of boron trihalide-methyl sulfide complex as indicated in Table 3. Tothis solution is added the desired number of equivalents of the aryl ether. Thereaction mixture is stirred at reflux and monitored by either TLC or GLC whereconvenient. When the starting material disappears, the reaction mixture ishydrolyzed by adding water (30 mL), stirring for 20 min and diluting withether. The organic pha is parated and washed with 1 M NaHCO3 and the phenol is subquentlytaken up with 1 N NaOH (3×20 mL). The combined NaOH washings are acidified and the product issubquently extracted into ether, dried (MgSO4) and the solvent isremoved in vacuum.
【H.Niwa, T. Hida and K. Yamada, Tetrahedron Lett.,1981,22, 4239】
三、BBr3/NaI/15-crown-5
这种体系为⽐BBr3更强的去甲基化⽅法。也可⽤于脱除烷基甲基醚。
Table3.Dealkylation of Alkyl Methyl Ethers with BBr3-NaI-15-crown-5i mate
a) Yield of isoated alcohol.
Typical Procedure. Cleavage of3-Phenylpropanol Methyl Ether.To a stirred solution of3-phenylpropanol methyl ether (103 mg, 0.687 mmol) in dry methylene chloride(0.5 mL) is added 0.3 Msolution of 15-crown-5 (13.7 mL, 6 equiv.) with NaI in methylene chloridefollowed by addition of 1 Msolution of BBr3 (2.1 mL, 3 equiv.) in methylene chloride at -30°C under argon. The reaction mixtureis stirred at the same temperature for 3 hrs, quenched by the addition ofsaturated aqueous NaHCO3 solution (2 mL) and worked up in the usualmanner. Chromatographic purification of the crude product gives the purealcohol (93 mg, 100%), identical in all respects with an authentic sample.
sign up with
【H.Niwa, T. Hida and K. Yamada, Tetrahedron Lett.,1981,22, 4239】
四、Me2BBr
⽂献报道，这个试剂去甲基化经由SN2机理，因此，⾮常有效的只是断裂C-O键，从⽽形成酚或醇，不易产⽣溴代副产物。
Table4.Cleavage of Ethers with (CH3)2BBr
skap
Typical Procedure. Cleavageof 1-Methoxydecane.To a cold (0°C),stirred solution of 1-methoxydodecane (1.03 mmol) and triethylamine (0.21 mmol,to neutralize traces of free acid) in dry methylene chloride (4.1 mL) underargon, is added a solution of dimethylboron bromide (1.34 M, 0.99 mL) in methylene chloride. The coolingbath is then removed and the resultant solution is then stirred at roomtemperature for 3 hrs. The reaction mixture is then cooled to 0°C, quenched with saturated aqueoussodium bicarbonate (2 mL) and diluted with ether (30 mL). The organic layer isparated, washed with saturated sodium bicarbonate (2 mL), water (2 mL) andbrine (2 mL). The aqueous washings are extracted with ether and the organiclayers are combined. After drying the resultant solution is concentrated andsubjected to flash chromatography to provide pure 1-dodecanol (89%).a) Yield of isoated Product.
【Y. Guindon, C. Yoakim and H. E. Morton, Tetrahedron Lett.,1983,24, 2969】
