Organic Syntheses, Coll. Vol. 6, p.41 (1988); Vol. 57, p.8 (1977).
A 500-ml., three-necked, round-bottomed flask equipped with a mechanical stirrer, a thermometer, and a calcium chloride drying tube
is charged with 15.0 g. (0.100 mole) of adamantanone (Tricyclo[22.214.171.124,7]decan-2-one)
, (Note 1)
, 25.4 g. (0.130 mole) of p-tolylsulfonylmethyl isocyanide (Note 2)
, (Note 3)
, 10 ml. (0.17 mole) of absolute ethanol (Note 4)
, and 350 ml. of 1,2-dimethoxyethane (Note 5)
. The stirred solution is cooled in an ice bath
to 5°, and 28 g. (0.25 mole) of potassium tert-butoxide
is added in portions at such a rate that the temperature is kept between 5° and 10° (Note 6)(Note 7)
. After the addition is complete, the ice bath
is removed and stirring is continued for 30 minutes. The reaction mixture is heated for 30 minutes at 35–40°, the stirred suspension is cooled to room temperature, and the precipitated potassium p-toluenesulfinate
is removed by filtration. The precipitate is extracted with three 50-ml. portions of 1,2-dimethoxyethane
, and the combined 1,2-dimethoxyethane
solutions are concentrated to a volume of 25–35 ml. on a rotary evaporator
. The concentrated solution is chromatographed (Note 8)
through a short column of alumina
using distilled petroleum ether
) as the eluent. The combined fractions are refluxed for 15 minutes with 1 g. of activated carbon (Note 9)
. After removal of the carbon
, the solution is concentrated to dryness in a rotary evaporator. The white solid residue is dried overnight in a vacuum desiccator
over silica gel
, yielding 13.5–14.5 g.
) of analytically pure 2-adamantanecarbonitrile
, m.p. 170–177° (Note 10)
Commercial absolute ethanol
Commercial 1,2-dimethoxyethane, "zur Synthese" quality, was purchased from E. Merck, Darmstadt
Scoops of solid potassium tert-butoxide (purchased from E. Merck, Darmstadt, and specified to be at least 95% pure)
were added over 20–30 minutes by temporarily removing the drying tube. At the beginning of the reaction much heat is evolved; therefore, the base should be added in small portions in order to keep the temperature below 10°. During the addition of the base, a precipitate is formed.
The submitters recommend using a 5 cm. by 10 cm. column packed with 200 g. of neutral alumina (activity I)
in petroleum ether (b.p. 40–60°), and eluting with 250-ml.
of this solvent. The checkers have found that the elution may require more solvent depending on the amount of residual 1,2-dimethoxyethane
: they recommend following the chromatography by GC analysis (see (Note 9)
Treatment with activated carbon (purchased from J. T. Baker Chemical Company)
can be omitted. In that case, removal of the solvent will provide 14–15 g.
) of a near-white product with a melting range of 160–180°
(see (Note 10)
). Despite this wide range, this material is over 99.8% pure, according to a GC analysis carried out at 190° on a 2-m. SE-30 column
. This high degree of purity was confirmed on three different types of column.
Melting points of 2-adamantanecarbonitrile
were determined in sealed tubes
to prevent sublimation. Varying values were found for the melting point which apparently is not a very reliable indication of the purity of this compound. Occasionally, a value as high as 184–187°
has been found by following the same procedure. Spectral properties of this product: IR (CHCl3
: 2240 (CN); 1
H NMR (CDCl3
), δ (multiplicity, number of protons): 1.4–2.4 (m, 14H), 2.9 (m, 1H).
The procedure described is an example of a more general synthetic method for the direct conversion of ketones into cyanides.3,4,5,6
The reaction has been carried out successfully with acyclic and cyclic aliphatic ketones, including numerous steroidal ketones and aryl-alkyl ketones. The conversion of diaryl or highly hindered ketones such as camphor
requires the use of a more polar solvent. In those cases, the dimethoxyethane
used in the present procedure should be replaced by dimethyl sulfoxide
By introduction of a slight modification, the method applies to aldehydes also.,7
This preparation is referenced from:
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