Chemistry Reference
In-Depth Information
Typical procedure. Mevinolin nitrile 1489 [1129]:
Mevinolin amide (125 mg, 0.30
mmol) was dissolved in anhydrous dichloromethane (1.5 mL; distilled from CaH
2
)
and the solution was stirred at 25
C under argon. The Burgess reagent was then
added in five 50 mg portions (1.05 mmol) over a period of 2 h. Stirring was con-
tinued for an additional 15 min, and then the mixture was applied directly to a
column of silica gel. Flash chromatography (ethyl acetate/hexane, 1:1) gave 99 mg
(82%) of mevinolin nitrile 1489 as a white crystalline solid.
Phenyl chlorothionoformate
A rather new method for the preparation of aromatic and aliphatic nitriles from
amides on various structures, under mild conditions and with a simple work-up,
was published in 1999. The reagent is phenyl chlorothionoformate, the reactions
are performed at room temperature, reaction times are 5-9 h, and yields are high
(81-95%) [1130].
General procedure. Nitriles from carboxamides (or thiocarboxamides) [1130]: Phenyl
chlorothionoformate (1.1 mmol) was added dropwise to a stirred, ice-cooled solu-
tion (or suspension) of the amide (1.0 mmol) in dry dichloromethane (5 mL) and
anhydrous pyridine (2.0 mmol) at such a rate that the temperature was kept below
5
C. The reaction mixture was then allowed to warm to room temperature for the
requisite time and was then quenched with water (2 mL). The resulting mixture
was extracted with dichloromethane (2
15 mL). The combined organic phases
were washed with saturated brine, dried (Na
2
SO
4
), and the solvent was removed in
vacuo to afford the crude product, which was purified by column chromatography
on silica gel. Pure nitriles were obtained in yields of 80-95%.
S
O
Cl
phenyl chlorothionoformate
Cyanuric chloride (CyCl)
Another new method for the conversion of primary amides to cyanides is dehy-
dration with cyanuric chloride (CyCl), which is used for the preparation of enan-
tiomerically pure cyanohydrins. (S)-2,2,5,5-Tetramethyl-1,3-dioxane-4-carbonitrile
1494 has been synthesized from the corresponding amide 1493 in 94% yield
[1131]. In practice, it is found that only two of the potential three units of CyCl
function as dehydration equivalents [1132].
Cl
CyCl
OO
OO
N
N
MTBE
DMF
rt, 1 h
CN
CONH
2
Cl
N
Cl
CyCl
1493
1494
95 %
