Phosgenation Reactions - Phosgenations - page 395

slowly heated to 40 C and maintained at this temperature for 5-8 h until the
amide had been consumed (TLC analysis). The mixture was then quenched with
H 2 O (2 mL) and extracted with dichloromethane (2 15 mL). The combined or-

ganic phases were washed with brine, dried (Na 2 SO 4 ), filtered, and the solvent was
removed in vacuo to afford the crude product, which was purified by column
chromatography on silica gel (EtOAc/hexane, 1:9, v/v) to give pure nitriles 1379 in
yields of 80-95%.

AlCl 3 /NaI (aluminum chloride/sodium iodide)
A new method has recently been described for the preparation of nitriles from
carboxamides or carbaldoximes using a combination of aluminum chloride and
sodium iodide (AlCl 3 /NaI) [1139]. The conversion of 1 equiv. of amide or oxime
requires 2 equiv. of AlCl 3 and 6 equiv. of NaI. Reactions are performed in refluxing
acetonitrile, the reaction time is 2.5 h, and yields are quoted as 80-95%.

Typical procedure. Benzonitrile from benzaldoxime [1139]: Anhydrous aluminum
chloride (0.264 g, 2 mmol) and sodium iodide (0.900 g, 6 mmol) were added to dry
acetonitrile (25 mL) and the mixture was stirred magnetically for 0.5 h at room
temperature under nitrogen. Benzaldoxime (0.121 g, 1 mmol) was added and stir-
ring was continued under reflux for a further 2.5 h. The progress of the reaction
was monitored by TLC. The reaction mixture was subsequently poured into ice-
cold 10% aq. ammonia solution and extracted with diethyl ether. The combined
organic layers were washed with water (2 100 mL), dried, and the solvent was

distilled off under reduced pressure to give benzonitrile; 0.098 g, 95% yield.

Acetonitrile (MeCN) with an aldehyde
Aldehydes can be used to catalyze water transfer from a primary carboxamide 1377
to acetonitrile to furnish the corresponding cyanide 1379 and acetamide as by-
product [1140]. The reactions are performed in refluxing acetonitrile, the reaction
time is 12 h, and yields of 64-92% have been reported for several aromatic and
aliphatic nitriles.

O MeCN O

+

R CN

CH 2 O
HCO 2 H

R NH 2 NH 2

64-92 %

1377 reflux, 12 h 1379

In contrast to the common methods described above, no sophisticated or powerful
dehydration reagent is needed and the reaction can easily be carried out on a large
scale. A reaction mechanism has been suggested, in which the aldehyde serves as a
relay for the water transfer from the amide to the acetonitrile solvent. The aldehyde
may be varied, but formic acid is essential for the reaction. Alkyne derivatives de-
compose under the reaction conditions, and both THP ethers and TBDMS groups
are unstable.