酮的α-氢易被取代，可以直接合成α-卤代酮。一般操作是将酮与卤素于醋酸、氯仿、DMF或水中反应。除卤素外， 硫酰氯、五卤化磷、过溴化吡啶氢溴酸盐（C5H5NH.Br3）、三卤化三甲基苄基铵盐等也可以做卤化试剂。 对称酮或只有一个取代方向的酮卤代时，可以良好产率（80~90%）生成α-卤代酮。不对称酮卤代，往往生成α-及α’-卤代酮的混合物。由于酮卤代的决定步骤是酮的烯醇化，因此，易形成烯醇的方向优先卤代。

例 2-甲基环己酮与亚硫酰氯作用， 多取代的α-氢优先氯代。

【 Warhoff E W et al. Org. Syn., Col. Vol. 1963, 4, 162】

若利用双（二甲基乙酰胺基）三溴化氢做溴化剂，可使不对称酮在少取代一边溴代。

【 Rodygin M Y, Mikhailov V A, Savelova V A. Zh. Org. Khim. 1994, 30, 827】

若将不对称酮首先转变成为一定构型的烯醇盐，继而卤代，是区域定向卤代的新方法。

【 BrummondK M, Gesenberg K D. Tetrahedron Lett. 1999, 40, 2231; Shi X X, Dai L X. J. Org.Chem. 1993, 28, 4596】

反应实例

A suspension of ketone 2A (700 mg, 2.17 mmol) in acetic acid(15 ml) was heated to 70℃,  followed by addition of bromine (347 mg, 2.17mmol).  After the mixture was stirred at 70℃for 3h, the solvent was evaporated and the residue was purified by columnchromatography to give the compound 2B (591 mg, 68%).

【Horvath, Amarylla; Nussbaumer, Peter;Wolff, Barbara; Billich, Andreas; J. Med. Chem.; EN; 47; 17; 2004; 4268 - 4276.】

Bromine (7.99 g,50 mmol) in CHCl₃ (20 ml) was added in a dropwise manner to astirred solution of 2, 5-dimethoxy-4-bromoacetophenone 2C (12.95 g, 40 mmol) in CHCl₃ (100 ml) at 5℃.  After the addition was completed, thereaction mixture was allowed to warm to room temperature and stirred for anadditional 2 h.  The mixture was pouredonto crushed ice, the organic portion was separated and washed with water,saturated NaHCO₃ solution, and again with water.  The solution was dried MgSO₄, andevaporated to dryness under reduced pressure to give a crude product.  The product was recrystallized from MeOH toyield 14.70 g (87%)of the desired bromoacetophenone 2D as a white solid.

【Glennon, Richard A.; Bondarev, MikhailL.; Khorana, Nantaka; Young, Richard; J. Med. Chem.; EN; 47; 24; 2004; 6034 -6041】

To a solution of 1-(2-aminopyrimidin-4yl) ethanone(412 mg, 3 mmol) in glacial acetic acid (1 mL) and 48% aq. HBr (0.3 mL),bromine (0.153 mL) in acetic acid (0.4 mL) was added and the resulting orangesolution was stirred at RT for1.5 hours. After diluting with ethyl acetate (15 mL), the precipitate was filteredand washed with ethl acetate thus affording the target compound as a whitishsolid (580 mg, 65%).

【 a)Lipinski, Christopher A.;Craig, Rebecca H.; Wright, Roger B.; J. Heterocycl. Chem.; 22; 1985; 1723-1726.  b) PHARMACIA and ITALIA S.p.A.; Publ.:  WO2005/14572  A1  (2005/02/17),  Appl.: WO2004-EP8853  (2004/08/06)】

Benzyltrimethylammonium tribromide (4.17 g, 10.7 mmol) was added to a solution ofCompound 2E (4.00 g, 10.7mmol) in CH₂Cl₂-MeOH (5:2, 25 mL).  The mixture was stirred at RT for 3 h.  At this time the reaction mixture wasconcentrated in vacuo and H₂O (15 mL) was added.  The mixture was extracted with diethyl ether(3 × 20 mL).  The combined organic extracts were washed withbrine (15 mL), dried over MgSO₄, filtered and concentrated in vacuo.The residue was purified by silica gel chromatography (hexanes:EtOAc, 3:1) toafford to afford Compound 2F(3.97 g, 8.8mmol, 82%) as a thick yellow oil.

【a)Ma, Chensheng; Wai, MingKwok; Wing, Sum Chan; Zuo, Peng; Kan, Jovi Tze Wai; Toy, Patrick H.; Phillips,David Lee; J. Am. Chem. Soc.; EN; SIR127; 5; 2005; 1463 - 1472.  b) Katsura, Yousuke; Nishino, Shigetaka;Inoue, Yoshikazu; Sakane, Kazuo; Matsumoto, Yoshimi; Morinaga, Chizu; Ishikawa,Hirohumi; Takasugi, Hisashi; J. Med. Chem.; 45; 1; 2002; 143 - 150.】

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