為了避免醇羥基在直接氯置換反應中可能產生的副反應，可先將醇用磺酰氯轉化成為相應的磺酸酯，再與親核性氯化試劑反應，生成所需的氯化烴。由于磺酰氯及其酯的活性較大，磺酰氯和氯置換反應均在較溫和的條件下進行，且常比氯素交換反應更加有效。常用的氯化劑有氯化鈉、氯化鋰、氯化鎂等。反應溶劑為丙酮、醇、DMF等極性溶劑。

 磺酸酯的氯置換反應合成示例

 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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