由醛肟制备腈

醛肟和一些羟基活化试剂作用进行顺式消除得到腈。常见的活化试剂有：乙酸酐，Tf2O，甲磺酰氯，Nonafluorobutanesulfonyl fluoride, BrCCl3/PPh3，TBBDA/PPh3，醋酸铜，SnCl2，GaCl3，FeCl3，oxalyl chloride/POPh3，T3P等。这些试剂将醛肟的羟基进行活化增强其离去性，有利于消除。

反应机理

机理以乙酸酐为例，其他试剂机理类似，Lewis酸则是直接活化羟基增强其离去性。

反应实例

General procedure: K2CO3 (3 mmol) was added to a stirredmixture of aldoxime (1.5 mmol) and 6 mL DMSO, followed by Ac2O (3 mmol).The resulting mixture was stirred at 50 C for a specified period (Table 2). Afterthe reaction was completed, 30mL water was added then extracted withCH2Cl2 (10 3 mL). The organic phase was washed with water (10 3 mL)then dried with

anhydrous Na2SO4. The solvent was evaporated under vacuumto give the nitrile products.

【Tetrahedron Letters; vol. 55; nb. 3; (2014); p.639 - 641】

General procedure: at room temperature, n-C4F9SO2F (20.0mmol, 2.0equiv.) was slowly dropped via syringe into a solution of substrate 1a (10.0mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 50.0mmol, 5.0equiv.) in CH2Cl2 (20mL). The resulting solution was stirred at this temperature for 10min. Evaporation under vacuum to remove volatile components offered residue

which was purified through silica gel column chromatography (eluted with a mixture of petroleum ether and ethyl acetate), generating nitrile 2a in 95percent yield.

【Chinese Chemical Letters; vol. 27; nb. 1; (2016); p. 96 - 98】

General procedure: A mixture of aldoximes (1 mmol) and imidazole (3 mmol) in anhydrous DCM (10-15 mL) was charged into an oven-dried round-bottom flask under nitrogen and the reaction mixture was stirred at r.t. for 20 min, after which triflic anhydride(0.4-1.0 mmol) was added dropwise via syringe under nitrogen, and the reaction mixture was allowed to stir at r.t. for a specific time (Table 1). Progress of the reaction was monitored by TLC and/or by GC-MS. Upon completion, the reaction mixture was quenched with dilute NaHCO3 solution and the product mass was extracted in DCM. The solvent was removed under reduced pressure to yield the crude product which was purified by prep TLC (ethyl acetate-hexane mixture) (80:20), to give the corresponding nitrile (61-88percent yield). The structure of the products was confirmed by comparison of their mp or bp, TLC, IR, GC-MS, 1H NMR and 13C NMR data with authentic samples obtained commercially or prepared by literature methods.

【Tetrahedron Letters; vol. 52; nb. 40; (2011); p. 5184 - 5187】

General procedure: BrCCl3 (650 mg, 3.3 mmol) was added to PPh3 (870 mg, 3.3 mmol) in dry CH2Cl2 (10 mL). The resulting mixture was stirred at room temperature for 20 min, during which time the solution turned from yellow to red–brownish in colour. Thereafter, 4-ethoxybenzaldoxime (4n, 500 mg, 3.05 mmol) was added. The reaction mixture was heated under reflux for 25 min. Then, triphenylphosphine (870 mg, 3.3 mmol) was added,and the mixture was stirred for 8 h at reflux. The cooled reaction mixture was concentrated under reduced pressure and subjected directly to column chromatography on silica gel (CH2Cl2–hexane 5 : 1) to give 2v as a colourless solid.

【Journal of Chemical Research; vol. 38; nb. 2; (2014); p. 80 - 84】

To a stirred suspension of 2 (48.21 g, 0.192 mol) in acetonitrile (386 mL) at 15 °C was added copper (II) acetate (0.523 g, 2.9 mmol) followed by acetic acid (13.1 mL, 0.229 mol). The resultant mixture was heated to reflux for 21 h after which time the completed reaction was cooled to 50 °C. Water (0.39 L) was added and the mixture was partially concentrated followed by dilution with water (290 mL) and cooled to 5 °C. 1 M NaOH in water (230 mL) was added and vigorous stirring was continued for 10 min. The suspension was filtered, the filter cake rinsed with water (500 mL) and dried to afford compound 3 (42.80 g, 0.183 mol, 95.6 percent yield) as dark gray powder.

【WO2015/57655; (2015); (A1) English】

General procedure: Aldoxime (1.0 mmol) and anhydrous FeCl3 (1.0 mmol) were intimately mixed with silica gel 60–120 mesh (1.0 g) in mortar and pestle. The resulting solid mixture was poured into a round-bottom flask (50 ml) and allowed to stir on magnetic stirrer at 110 °C for an appropriate time (Table 2). The progress of the reaction was monitored by thin-layer chromatography (TLC). After completion of the reaction, the reaction mixture was extracted with ethyl acetate (3 15 ml) and washed several times with water. The combined organic mixture was dried over anhydrous Na2SO4, concentrated, and purified by column chromatography on silica gel 60–120 mesh using petroleum ether/ethyl acetate as eluent to afford pure nitrile.

【Synthetic Communications; vol. 46; nb. 8; (2016); p.685 - 691】

General procedure: A solution of oxime (0.5 mmol) and SnCl2.2H2O (Method 1A, under open air) or GaCl3 (Method 1B, under argon) (0.05 mmol) in dry MeCN (1 mL) was stirred at 80 °C and monitored by TLC. After completion of the reaction, the mixture was purified by flash chromatography.

【Tetrahedron Letters; vol. 57; nb. 50; (2016); p. 5700 - 5702】

To the mixture of PPh3 (0.525 g, 2 mmol) and TBBDA (0.287 g, 0.53 mmol) in dry acetonitrile (5 mL), 4-nitrobenzaldehyde oxime (0.166 g, 1 mmol) was added. The mixture was stirred at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction (Table 1), the solvent was evaporated. The crude products were purified by short-column

chromatography (packed with silica gel, using n-hexane/ethyl acetate (8:2) as eluent) to achieve the desired 4-nitrobenzonitrile with 0.13 g, 92percent yield.

【Chinese Chemical Letters; vol. 24; nb. 12; (2013);p. 1123 - 1126】

General procedure: To a solution of triphenylphosphine oxide (14 mg, 0.050 mmol) in either CHCl3, CDCl3 or EtOAc (2.0 mL) was added oxalyl chloride (102 μL, 1.21 mmol) and the reaction mixture was stirred for 5 min. The appropriate oxime (1.00 equiv) as solution in either CHCl3, CDCl3 or EtOAc (1.0 mL) was then added over 0.5 h via syringe pump at room temperature

and the reaction mixture was stirred for a further 0.5 h at room temperature after which the solvent was removed in vacuo. Purification by flash chromatography (silica, 10-100percent Et2O/pet. ether) gave the pure nitriles.

【Tetrahedron; vol. 68; nb. 13; (2012); p. 2899 - 2905】

To a solution of aldoxime (0.01 mol) in THF (10 mL) was added T3P (15 mol percent, 50percent soln in EtOAc) and the resulting reaction mixture was stirred at room temperature for 1-2 h under nitrogen atmosphere. When the reaction was completed as confirmed by TLC, the solvent was removed under vacuum and the residue was diluted with water (20 mL). The product was

extracted with ethyl acetate (2 .x. 20 mL) and the combined organic phase was washed with saturated NaHCO3 solution (1 .x. 10 mL) and brine. The organic phase was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure to afford the desired nitriles in good purity.

【Tetrahedron Letters; vol. 52; nb. 10; (2011); p. 1074 - 1077】