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     在有机合成中，腈水解为酰胺是一类很重要的反应，最常用条件当属酸碱水解。然而，当反应底物中含有敏感基团时，剧烈的反应条件往往会带来较多的意想不到的副反应。今天小编给大家总结一下腈在温和条件下水解为酰胺的反应条件，希望大家在平时的工作中可以有所帮助。

1-碱性条件

2015年，Jyotirmayee Dash团队报道了叔丁醇钾在无水条件下的水解反应，反应条件温和，具有良好的底物范围和良好的反应收率。对绝大部分产物来说，只需要过滤和简单的洗涤就可以得到纯品（J. Org. Chem. 2015, 80, 4148−4151）。

操作步骤：A flame-dried flask fitted with a magnetic stir bar was charged with benzonitrile (103 mg, 1.0 mmol, 1.0 equiv) and KOt Bu (336 mg, 3.0 mmol, 3.0 equiv), and dry toluene (4 mL/mmol) was added. The reaction mixture was stirred at room temperature for 5 h under nitrogen atmosphere, and progress of the reaction was monitored by TLC. Upon completion, the reaction mixture was treated with water (10 mL). The solid amide product was filtered, washed with water, and dried under vacuum to provide the corresponding amide 2 in 91% (110 mg, 0.91 mmol) as a white solid.

2-钯催化方法

钯催化也是一类温和的方法，甲酯可以得到很好的保留（US2011/275627, 2011, A1）。

操作步骤：A solution of methyl 3-{3-[(3-cyanophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (125 mg, 0.257 mmol), palladium(II) chloride (9.1 mg, 0.051 mmol), and acetamide (152 mg, 2.57 mmol) in THF (1.5 mL) and water (0.5 mL) is heated at 50° C. for 3 h then cooled to 23° C. and partitioned between water and Et2O. The organics are washed with water, dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by flash chromatography (SiO2, hexanes to 75percent EtOAc in hexanes) gives methyl 3-{3-[(3-carbamoylphenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(propan-2-yl)indolizin-2-yl}-2,2-dimethylpropanoate (114 mg, 88percent).

3-氧化方法

氧化剂氧化方法（US2009/186873, 2009, A1）。

操作步骤：To a stirred solution of 3-fluoro-4-(4-formyl-phenoxy)-benzonitrile (17.72 g, 1.00 equiv; 73.460 mmol) in dimethyl sulfoxide (75 mL), add potassium carbonate (0.5 equiv, 5.08 g). Cool the mixture to 10° C. and add hydrogen peroxide (35percent in water, 7.4 mL, 1.05 equiv) dropwise, keeping the internal temperature below 40° C. After the addition, stir the reaction mixture for 3 h. Pour the mixture over H2O-ice (300 mL). Filter the solid over filter paper, wash the solid with water twice, and dry under reduced pressure to obtain Intermediate 2. (17.30 g, 91percent yield).

4-Wilkinson催化剂方法

2009年，Hee-Yoon Lee团队报道了Wilkinson催化剂催化的使用醛肟作为水源的无水条件下腈转变为酰胺，反应十分高效（Org. Lett. 2009, 11, 24, 5598-5601）。

操作步骤：To an oven-dried 1mL v-vial were added various nitriles (0.5 mmol), acetaldoxime (150 µL, 2.5 mmol), RhCl(PPh3)3 (4.6 mg, 0.005 mmol) and toluene (0.125 mL). The mixture was vigorously stirred at 110 oC for 4-5 h and directly purified by a silica gel column chromatography (ethyl acetate/n-hexane).

5-酶催化方法

酶催化方法（Tetrahedron Letters 51 (2010) 1639–1641）。

操作步骤：The nitrile substrate was added to a mixture of organic co-solvent  and 100 mM potassium phosphate buffer, pH 7.0 (giving a total reaction volume of 5.0 ml), and the enzyme (as CFE or PE as detailed below) was added. The solution was mixed using a standard laboratory magnetic stirrer for 17–24 h at 30 C whilst following the progress of the reaction by TLC. The reaction medium was extracted with EtOAc (3  5.0 ml) and the organic extract dried with MgSO4 and analysed by GC–MS. Compound identities were established by comparison with published NMR, IR and melting point data.

6-Lewis酸方法

Lewis酸方法（Org. Process Res. Dev.2019, 23, 1918−1925）。

操作步骤：

A reaction flask was charged with 4-(4-methylpiperazin-1-ylmethyl)-benzonitrile (20) (43.1 g, 0.2 mol), isopropyl alcohol (100mL), water (3.6 mL, 0.2 mol), nano-ZnO (0.81 g, 0.01 mol),and KOH (1.1 g, 0.02 mol). The reaction mixture was heatedto reflux for 6−8 h. After a portion of isopropyl alcohol hadbeen distilled off, the mother liquor was filtered by hotfiltration to remove the catalyst residue. The reaction mass waspoured into a beaker and brought to room temperature for 8 h.The precipitated solid was isolated byfiltration and placed intoa beaker charged with 100 mL of distilled water. The mixturewas heated to 90°C for 10 min. Hotfiltration was carried out,and the mother liquor was brought to room temperature. Thesolid product was filtered, washed with water, and dried toyield 4-(4-methylpiperazin-1-ylmethyl)benzamide (18) as white granular crystals (43.5 g, yield: 93.1%)

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