脂肪鹵代物的合成——醇和溴化磷的反應

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  用三溴化磷、五溴化磷對醇羥基做親核取代反應也是經典的溴化反應。這類溴化劑的活性比氫溴酸大,與后者相比,重排副反應也較少。其中,三溴化磷應用最多,前者效果比較好,也可以由溴和磷在反應中直接生成,使用方便。

      三溴化磷和醇進行反應時,首先生成亞磷酸的單、雙或三酯的混合物(9)和溴化氫,然后,由于傾向于形成磷;≒=O)而使(9)中烷氧鍵發生斷裂,于是溴素負離子對酯分子中親電性烷基作親核取代反應,生成溴化物。

       上述親核取代過程,大多屬于 SN 2 機理,因此,光學活性醇在與三溴化磷反應后的主要產物常常為構型翻轉的溴化物。但是,由于亞磷酸酯反應的立體選擇性不高,故會發生一定比例的外消旋化。

       對于某些易發生重拍的醇(仲醇、β位具有叔碳取代基的伯醇等),由于 S N 1 機理可能性增加,則隨著所用溴化磷以及其用量、反應條件不同,其收率和重排副產物的比例也不同。

醇和溴化磷反應的方法示例

Example A: 2-(Bromomethyl)thiophene

      A solution of PBr 3 (59 ml, 0.63 mol) in Et 2 O (150 ml) was added during 7 hours to a stirred solution of 2-hydroxymethylthiophene (30.2 g, 0.26 mol) in Et 2 O (250 ml). The  mixture was stirred overnight at room temperature, poured into ice-water and extracted with Et2O. The organic extract was washed with water until neutrality, dried and concentrated in vacuo. The residue was fractionally distilled to give 38.1g (83%) of target compound (87℃/13 Torr.)

Example B :TETRAHYDROFURFURYL BROMIDE

     In a 500-ml. three-necked flask, fitted with a mechanical stirrer,

thermometer, separatory funnel, and calcium chloride tube, are placed 96 g.(56.5 ml., 0.36 mole) of redistilled phosphorus tribromide (b.p.

174–175°/740 mm.) and 50 ml. of dry benzene. From the separatory funnel, 15 g. of dry pyridine is added with stirring over a period of 15 minutes. The flask is then surrounded by an ice-salt mixture, and the contents are cooled to ?5°. A mixture of 102 g. (1 mole) of redistilled tetrahydrofurfuryl alcohol (b.p. 79–80°/20 mm.) and 5 g. of dry pyridine (total pyridine, 20 g., 0.25mole) is added slowly from the dropping funnel with stirring over a period of 4 hours. During this time the internal temperature is kept at ?5° to ?3°.Stirring is continued for 1 hour longer, and the cooling bath is then allowed to warm up to room temperature.

    The mixture is allowed to stand for 24–48 hours (Note 1) and is then

transferred to a 500-ml. Claisen flask. Two small portions of benzene are used for rinsing the flask. The benzene is distilled by reducing the pressure gradually to about 60 mm. and heating the flask gently in an oil bath (not above 90°). After the benzene has been removed, the pressure is reduced to 5–10 mm. and the bath is heated slowly to 150–155° until no more material distils (Note 2). The crude distillate (110–126 g.) is redistilled through an efficient column, and the purified tetrahydrofurfuryl bromide is collected at 69–70°/22 mm. (61–62°/13 mm., 49–50°/4 mm.) (Note 3). The yield is 90–102 g. (53–61%).

Example C :2-(2-Chloro-3, 4-dimethoxyphenyl)ethyl Bromide

   PBr 3 (3.8 g, 14 mmol) in 30 ml of Et 2 O was added to a stirred solution of 6.03 g (28mmol) of 2-(2-Chloro-3, 4-dimethoxyphenyl) ethanol in 30 ml of Et 2 O. The mixture was rfluxed for 1 hour, cooled to 5℃, and cautiously poured onto 60 g of crushed ice. After the Et2O phase was separated and washed successively with a saturated aqueous solution of NaHCO3 , H2O, and brine, it was dried (Na2SO4 ) and concentrated. The residual liquid was distilled, and the fraction (5.3 g, 68%), b.p.: 112-115℃ (0.15 torr).



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