酰卤(酰氯、酰溴和酰氟)与氨或胺作用是合成酰胺的简便的方法。通过酰氯、酰溴与脂肪族、芳香族胺均可迅速酰化，以较高的产率生成酰胺。但酰氟对水和其他亲核试剂较为稳定。一般酰氯、酰溴与胺反应是放热的，有时甚至极为激烈，因此通常在冰 冷却下进行反应，亦可使用一定量的溶剂以减缓反应速度。常用溶剂为二氯乙烷、乙 醚、四氯化碳、甲苯等。由于反应中生成的卤化氢，因此需要用碱除去卤化氢，以防止其与胺成盐。有机碱和无机碱均可用于此类反应，常用的有机碱有三乙胺、吡啶等， 常用的无机碱有 Na2CO3, NaHCO3,  K2CO3, NaOH, KOH 等。在研究中我们发现，许多反应用无机碱反应更干净且容易处理。 

       酰氯主要通过二氯亚砜和三氯氧磷的制备，高沸点的底物来说，二氯亚砜是合适的试剂；一般的酸在二氯亚砜回流数小时后，蒸掉过量二氯亚砜及溶剂后，再用些甲苯带一下残余的二氯亚砜即可用于下步反应。对低沸点的底物来说，则使用三氯氧磷较 为方便，主要由于低沸点很容易蒸馏出来。对于α-氨基酸，由于相应的酰氯在加热会分解，因而一般不通过二氯亚砜和三氯氧磷的制备。当分子中有对酸敏感的官能团存在时，无法使用二氯亚砜，一般采用等当量的草酰氯和碱，一锅发生酰氯再直接用于下步反应，近也有文献报道应用三氯均三嗪在碱存在下可一锅将酸转化为酰氯。由于酰氯的活性太高，一般很难鉴定，有时为了判断酰氯是否生成，一般取出一点加入过量的苄胺或甲 醇等，通过 TLC 确认反应进行的程度，也可以蒸干溶剂通过 HPLC, LC-MS 或 NMR 确 认。α-氨基酰氯一般也通过以上两种方法合成。芳香酰氯相对烷基酰氯要稳定的多，例 如苯甲酰氯加入水中也要近半个小时才能分解完全。

     酰氟要比酰氯稳定的，其对水和其他亲核试剂都较为稳定，其可通过三氟均三嗪在吡啶的存在下制备(Tetrahedron lett. 1991,32（10)，1303)。并可以通过层析分离出来。酰氟对水和其他亲核试剂，易于保存和使用方便，我们有时可以利用它进行酰胺类化合物 库的合成。

对于一些位阻较大活性很低的芳胺，往往即使用酰氯也有可能不发生反应，此时我们需要加入催化剂如 DMAP 等，有时也可不加任何碱直接由胺和酰氯高温回流反应得到酰胺。 

1、酰卤的制备示例 

1.1应用二氯亚砜合成酰氯实例。

     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。

1、2 用草酰氯合成酰氯示例

      Compound 42 (4.19 g, 13.94 mmol) was dissolved in 20 mL CH2Cl , oxalyl chloride (4.25mL, 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. 

1、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). 

 1、4 用三氟均三嗪合成酰氟示例 

     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.