由芳环的 Friedel-Crafts 反应合成芳基酮

  • A+

 Friedel-Crafts 反应是在芳环上引入酮基的非常好的方法。傅-克酰基化反应Friedel-Crafts acylation)的反应机制和烷基化是类似的,也是在催化剂的作用下,首先生成酰基正离子,然后和芳环发生亲电取代。

      常用的酰基化试剂是酰卤(主要是酰氯和酰溴)和酸酐。常用的催化剂是三氯化铝。由于 AlCl 3 能与羰基络合,因此酰化反应的催化剂用量比烷基化反应多,含一个羰基的酰卤为酰化试剂时,催化剂用量要多于 1mol,反应时,酰卤先与催化剂生成络合物,少许过量的催化剂再发生催化作用使反应进行。如用含两个羰基的酸酐为酰基化试剂,因同样的原因,催化剂用量要多于 2mol,络合物的结构如下:

       酰基是一个间位定位基,当一个酰基取代苯环的 H 后,苯环的活性就降低了,反应即行停止,不会生成多元取代物的混合物,因此芳烃的酰基化反应产率一般较好。例如:

      傅-克酰基化反应是不可逆的,不会发生取代基的转移反应。鉴于以上两个特点,傅-克酰基化反应在制备上很有价值,工业生产及实验室常用它来制备芳香酮,例如:

      这不但是合成芳香酮的重要方法之一,同时也是芳环烷基化的一个重要方法,因生成的酮可以用克莱门森(Clemmensen,E.)还原法将羰基还原成亚甲基而得到烃。

    与傅-克烷基化反应类似,有间位定位基的芳烃极难发生傅-克酰基化反应,因此在酸性条件下苯胺的傅-克酰基化反应很难进行,因为氨基会与酸成盐而转变为间位定位基,可通过乙酰化将氨基保护起来,反应结束后,再水解除去乙酰基。例如邻氨基苯乙酮可采用如下合成路线制备:

      酚类和芳香醚类化合物都有强活性的邻对位定位基,反应时可以选用比较弱的催化剂如 ZnCl 2 、多磷酸(PPA)等。例如:

由于在邻位位阻较对位大,如对位无取代基主要进入对位。

   The alkylation or acylation of aromatic compounds catalyzed by aluminum chloride or other Lewis acids:

由 Friedel-Crafts 反应合成酮反应示例:

     To a 5 L three necked flask equipped with a stirrer, dropping funnel, condenser, and dry tube is added 1.5 L of dry, freshly distilled carbon tetrachloride. To this is added 454 g (3.3mol) of reagent grade granular aluminum chloride and the mixture is cooled to about 5℃ by means of an ice-water bath. Acetyl chlorides (275 g, 3.5 mol) are added dropwise to the cooled mixture over a 5-10 min interval. This addition is then followed with the dropwise addition of the appropriate xylene isomer [o-xylene, 300ml (2.5 mol), m-xylene 300ml (2.5mol), or p-xylene 275 ml (2.3 mol)] at 10-15℃, which takes about 1-2 h. The mixture is stirred at room temperature for 2 h and then allowed to stand overnight at room temperature. The mixture is poured into a mixture of 5 kg of ice and 700ml of concentrated HCl. The lower carbon tetrachloride layer is separated, washed twice with 250 ml portions of water, once with 500 ml of 2% NaOH solution, and then several times with water until the washings are neutral. The Carbon tetrachloride is distilled off at atmospheric pressure and the residue is fractionally distilled to give 280 g (75%) of 3,4-dimethylacetophenone, bp 103℃ (6 mm), 140 g (43%) of 2,5-dimethylacetophenone, bp 85-86℃ (3 mm) and 225 g (61%) of 2,4-dimethylacetophenone, bp 90℃ (6 mm).

       An aromatic compound (1 mmol) was added to a mixture of ZnO (powder, 0.04 g, 0.5 mmol) and acid chloride (1 mmol) at room temperature and stirred with a magnetic stirrer. Color (usually pink, but in few cases green or blue) developed immediately and darkened with progress of the reaction. The reaction mixture was kept at room temperature with occasional stirring for a certain period of time as required to complete the reaction (monitored by TLC). The solid mass was then eluted with dichloromethane (20 mL), and the dichloromethane extract was then washed with an aqueous solution of sodium bicarbonate and dried over  anhydrous sodium sulfate. Evaporation of solvent furnished practically pure the corresponding product. The identity of these compounds was easily established by comparison of their 1H NMR spectra with those of authentic sample.


weinxin
我的微信
关注我了解更多内容

发表评论

目前评论:0