Organic Syntheses, Coll. Vol. 5, p.670 (1973); Vol. 49, p.75 (1969).
. A mixture of 4.53 g. of cis- and trans-4-aminocyclohexanecarboxylic acid
and 30 ml. of Dowtherm A (Note 6)
is heated as rapidly as possible to reflux temperature. Heating is continued for 20 minutes during which time the water formed is allowed to distill away; at the end of this time, solution has taken place. The solution is allowed to cool to room temperature and is diluted with 100 ml. of isooctane
. The solution is extracted three times with 50-ml. portions of water. The combined water extracts are treated with charcoal
, filtered, and concentrated to dryness under reduced pressure. The residue is crystallized from cyclohexane
giving 3.20–3.33 g.
) of 3-isoquinuclidone
, m.p. 197–198° (Note 5)
Purchased from B. L. Lemke and Co., Inc., 199 Main Street, Lodi, New Jersey. The checkers used material from Eastman Organic Chemicals Department.
A mixture of 5.26 g. of rhodium chloride trihydrate
, 0.34 g. of palladium chloride
, 18 g. of carbon (Darco G-60)
, and 200 ml. of water is rapidly stirred and heated to 80°. Lithium hydroxide hydrate (2.7 g.)
dissolved in 10 ml. of water is added all at once and the heating stopped. The mixture is stirred overnight, filtered, and washed with 100 ml. of 0.5 v/v% aqueous acetic acid
. The product is dried under reduced pressure at 65°, giving 20.6–21 g.
of the catalyst. One gram of this catalyst consumes 0.0022–0.0028 mole of hydrogen
in aqueous suspension.2
The checkers found that the reduction requires 4–5 days, whereas the submitter reported the reaction requires 24 hours. Fresh catalyst is added whenever the rate of hydrogen
uptake significantly decreases. When fresh catalyst is added to the reaction vessel, it is important that it first be wet with solvent and that the hydrogen
be well evacuated. Opening the mixture to the atmosphere without careful evacuation will produce a hydrogen-oxygen
mixture which may explode on contact with fresh catalyst.
It is necessary to concentrate the solution to one-fifth volume before crystals form.
The submitters report the preparation scaled up by fifty-fold with similar yields and purities.
Purchased from Dow Chemical Co., Midland, Michigan.
The described method of preparation of 3-isoquinuclidone has the following advantages: The isolation of the cis
form of 4-aminocyclohexane carboxylic acid
is not required in order to obtain a good yield; the amount of 3-isoquinuclidone
that can be prepared at a time is limited only by the size of available equipment; the yield is excellent and the workup is easy and straightforward.
has been found to be an excellent substitute for camphor
for molecular weight determinations.2
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