为了避免醇羟基在直接氯置换反应中可能产生的副反应，可先将醇用磺酰氯转化成为相应的磺酸酯，再与亲核性氯化试剂反应，生成所需的氯化烃。由于磺酰氯及其酯的活性较大，磺酰氯和氯置换反应均在较温和的条件下进行，且常比氯素交换反应更加有效。常用的氯化剂有氯化钠、氯化锂、氯化镁等。反应溶剂为丙酮、醇、DMF等极性溶剂。

 磺酸酯的氯置换反应合成示例

 Example A: The preparation Geranyl chloride

A dry, 1-L., three-necked, round-bottomed flask is equippedwith an overhead mechanical stirrer, a 125-ml. pressure equalizing dropping funnel fitted witha rubber septum, and a nitrogeninlet tube. The system is flushed with nitrogen, and 15.4 g. (0.100 mole) of geraniol, 35 ml. ofdry hexamethylphosphoric triamide, 100 ml. of anhydrous diethyl ether, and 50 mg. of triphenylmethane are placed in the flask.The stirred solution is cooled to 0° with an ice bath,and 63 ml. (0.1 mole) of 1.6 M methyllithium in ether is injected into the additionfunnel. The methyllithium solution is added dropwiseover a period of 30 minutes. After the addition is complete, the funnel isrinsed by injecting 5 ml. of dry ether.

A solution of 20.0 g. (0.105 mole) of p-toluenesulfonyl chloride in 100 ml. ofanhydrous ether is injected into the additionfunnel and added over a period of 30 minutes to the stirred, red, 0° reactionmixture. The red color immediately disappears upon addition. After addition iscomplete, 4.2 g. (0.0990 mole) of anhydrous lithium chloride is added. The reactionmixture is warmed to room temperature and stirred overnight (18–20 hours), duringwhich time lithium p-toluenesulfonate precipitates.

After a total of 20–22hours, 100 ml. of etheris added, followed by 100 ml. of water. The layers are separated, and theorganic phase is washed four times with 100-ml. portions of water, and finallywith 100 ml. of saturated sodiumchloride. After drying the organic phase over anhydrous magnesiumsulfate, the solvent is removed on a rotary evaporator. The crudeproduct is transferred to a 50-ml. flask and distilled through a 20-cm. Vigreuxcolumn, yielding 14.1–14.6 g.(82–85%) of geranyl chloride as a colorless liquid, b.p. 78–79° (3.0 mm.).    

【 Organic Syntheses, Coll. Vol. 6, p.638;Vol. 54, p.68】

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