A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1977, 57, 8
DOI: 10.15227/orgsyn.057.0008
Submitted by O. H. Oldenziel, J. Wildeman, and A. M. van Leusen1.
Checked by Teresa Y. L. Chan and S. Masamune.
1. Procedure
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[,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 (b.p. 40–60°) 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. (84–90%) of analytically pure 2-adamantanecarbonitrile, m.p. 170–177° (Note 10).
2. Notes
1. Commercial adamantanone (Aldrich Chemical Company, Inc.) was used; the synthesis of adamantanone is described in Org. Synth., Coll. Vol. 6, 48 (1988).
2. The synthesis of p-tolylsulfonylmethyl isocyanide is described in Org. Synth., Coll. Vol. 6, 987 (1988).2 The light-brown compound, m.p. 111–114°, was used without further purification.
3. p-Tolylsulfonylmethylisocyanide was used in slight excess to effect complete conversion of the adamantanone, which otherwise is difficult to remove from the final product.
4. Commercial absolute ethanol was used.
5. Commercial 1,2-dimethoxyethane, "zur Synthese" quality, was purchased from E. Merck, Darmstadt.
6. 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.
7. The reaction has also been carried out successfully with sodium ethoxide.3
8. 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)).
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. (87–93%) 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.
10. 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) cm.−1: 2240 (CN); 1H NMR (CDCl3), δ (multiplicity, number of protons): 1.4–2.4 (m, 14H), 2.9 (m, 1H).
3. Discussion
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 and β,β-dimethyl-α-tetralone requires the use of a more polar solvent. In those cases, the dimethoxyethane used in the present procedure should be replaced by dimethyl sulfoxide.6 By introduction of a slight modification, the method applies to aldehydes also.,7
2-Adamantanecarbonitrile was prepared previously by a more laborious method,8 also starting from adamantanone, in 46% overall yield.
The hydrolysis of 2-adamantanecarbonitrile with hydrogen bromide in acetic acid provides a useful route to 2-adamantanecarboxylic acid (m.p. 143–144°),9 which the submitters obtained in 95% yield. Stetter and Tillmans8 reported a yield of 62% starting with impure 2-adamantanecarbonitrile.
This preparation is referenced from:

References and Notes
  1. Department of Organic Chemistry, Groningen University, Nijenborgh 16, 9747 RG Groningen, The Netherlands.
  2. A. M. van Leusen, G. J. M. Boerma, R. B. Helmholdt, H. Siderius, and J. Strating, Tetrahedron Lett., 2367 (1972); A. M. van Leusen, R. J. Bouma, and O. Possel, Tetrahedron Lett., 3487 (1975).
  3. O. H. Oldenziel and A. M. van Leusen, Synth. Commun., 2, 281 (1972).
  4. O. H. Oldenziel and A. M. van Leusen, Tetrahedron Lett., 1357 (1973).
  5. J. R. Bull and A. Tuinman, Tetrahedron, 31, 2151 (1975).
  6. O. H. Oldenziel, D. van Leusen, and A. M. van Leusen, J. Org. Chem, 42., 3114 (1977).
  7. A. M. van Leusen and P. G. Oomkes, Synth. Commun., 10, 399 (1980).
  8. H. Stetter and V. Tillmans, Chem. Ber., 105, 735 (1972).
  9. For other syntheses, see A. H. Alberts, H. Wynberg, and J. Strating, Synth. Commun., 2, 79 (1972) and D. Farcasiu, Synthesis, 615 (1972).

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

silica gel

petroleum ether

ethanol (64-17-5)

acetic acid (64-19-7)

hydrogen bromide (10035-10-6)

carbon (7782-42-5)

sodium ethoxide (141-52-6)

camphor (21368-68-3)

dimethyl sulfoxide (67-68-5)

1,2-dimethoxyethane (110-71-4)

dimethoxyethane (534-15-6)

Tricyclo[,7]decane-2-carbonitrile (35856-00-9)

Tricyclo[,7]decan-2-one (700-58-3)


2-adamantanecarboxylic acid (15897-81-1)

p-Tolylsulfonylmethyl isocyanide,
p-Tolylsulfonylmethylisocyanide (36635-61-7)

potassium tert-butoxide (865-47-4)

potassium p-toluenesulfinate