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酰鹵是有機(jī)合成中非常重要的中間體，可以由其制備酰胺和酯。 酰氯主要通過二氯亞砜，草酰氯和三氯氧磷制備，另外試劑也有用到。

試劑較貴，在氯化亞砜中加入少量DMF催化會(huì)直接生成試劑中間體，接著生成酰氯。

高沸點(diǎn)的底物來說，二氯亞砜是最合 適的試劑；一般的酸在二氯亞砜回流數(shù)小時(shí)后，蒸掉過量二氯亞砜及溶劑后，再用些甲 苯帶一下殘余的二氯亞砜即可用于下步反應(yīng)。對低沸點(diǎn)的底物來說，則使用三氯氧磷較 為方便，主要由于低沸點(diǎn)很容易蒸餾出來。對于α-氨基酸，由于相應(yīng)的酰氯在加熱會(huì)分 解，因而一般不通過二氯亞砜和三氯氧磷的制備。當(dāng)分子中有對酸敏感的官能團(tuán)存在時(shí)， 無法使用二氯亞砜，一般采用等當(dāng)量的草酰氯和堿，一鍋發(fā)生酰氯再直接用于下步反應(yīng)， 最近也有文獻(xiàn)報(bào)道應(yīng)用三氯均三嗪在堿存在下可一鍋將酸轉(zhuǎn)化為酰氯。由于酰氯的活性 太高，一般很難鑒定，有時(shí)為了判斷酰氯是否生成，一般取出一點(diǎn)加入過量的芐胺或甲 醇等，通過TLC 確認(rèn)反應(yīng)進(jìn)行的程度，也可以蒸干溶劑通過HPLC, LC-MS 或NMR 確 認(rèn)。α-氨基酰氯一般也通過以上兩種方法合成。芳香酰氯相對烷基酰氯要穩(wěn)定的多，例 如苯甲酰氯加入水中也要近半個(gè)小時(shí)才能分解完全。

酰氟要比酰氯穩(wěn)定的，其對水和其他親核試劑都較為穩(wěn)定，其可通過三氟均三嗪在吡啶的存在下制備(Tetrahedron lett. 1991,32（10)，1303)。并可以通過層析分離出來。酰氟對水和其他親核試劑，易于保存和使用方便，我們有時(shí)可以利用它進(jìn)行酰胺類化合物庫的合成。

反應(yīng)實(shí)例

1、應(yīng)用二氯亞砜合成酰氯示例（Practical organic chemistry）

Fit a 100 mL two-necked flask with a dropping funnel and a reflux condenser connected at the top to a gas absorption trap. Place 36 g (21.5 mL, 0.3 mol) of redistilled thionyl chloride in the flask and 22 g (23mL, 0.25 mol) of butyric acid in the separatory funnel. Heat the flask gently on a water bath, and add the butyric acid during the course of 30-40 minutes. When all the acid has been introduced, heat was on a water bath for 30 minutes. Rearrange the apparatus and distillation: collect the crude acid chloride boiling between 70 and 110 ℃.

Finally, restil from a flask provided with a short fractionating column and collect the butyryl chloride at 100-101 ℃. The yield is 23 g (86 %).

Note: Wrap a piece of absorbent cotton wool around the stem of the reflux condenser above the joint of the reaction flask to prevent condensed。

2 、用草酰氯合成酰氯示例（J. Med. Chem. 1996, 39, 5183-5191.）

Compound 42 (4.19 g, 13.94 mmol) was dissolved in 20 mL CH2Cl2, oxalyl chloride (4.25 mL, 48.40 mmol) was added at room temperature, the resultant mixture was stirred at room temperature for 30 min and then the mixture was gently warmed under reflux for 30 min. After the mixture was concentrated in vacuo, the residue was dissolved in THF, and the solution was again concentrated in vacuo to offer quantitatively the crude chloride 43.

3、 用三氯均三嗪合成酰氯示例【】

To a mixture of P-nitrobenzoic acid (1.67g, 0.01 mol) and 2,4,6-Trichloro-[1,3,5]triazine 44 (1.84g, 0.01mol) in acetone (20 mL) was added TEA (1.01, 0.01 mol) and the mixture was stirred for 3hr, filtrated to remove the separated dichlorohydroxy-s-triazine derivative, and the filtrate concentrated under reduced pressure. The residue was extracted with CCl4 and the solvent removed to give the desired acid chloride 46 (yield 58 %). (Note: the residue insoluble in CCl4 was found to be the unreacted carboxylic acid).

4 、三氟均三嗪合成酰氟示例【Tetrahedron lett. 1991,32（10），1303】

Typical experimental detail: equimolecular amount of the amino acid, pyridine and cyanuryl fluoride are mixed and stirred for 3~4 hours in dichloromethane at room temperature. At that time, ice-water is added to the reaction mixture and the precipitated canuric acid is filtered off the organic phase is dried and evaporated to dryness, which generally leaves the pure amino acid fluoride in crystalline form.

5、(點(diǎn)擊查看詳細(xì)內(nèi)容)

在加熱條件下，催化量的紅磷或三鹵化磷(PCl3 or PBr3)催化羧酸進(jìn)行鹵代生成α-鹵代羧酸的反應(yīng)被稱為 Hell-Volhard-Zelinsky反應(yīng) 。

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