Mechanism A
O
OH
N
O
N
Cl
+
Cl
O
N
N
R1R2CHOH
N
N
N
N
3
3
3
+
+
N
N
H
O
N
N
O
OH
H
O
H
O
Cl
Cl
Cl
O
H
O
R1 R2
R1 R2
Mechanism B
O
R1
N
O
R1
R1
H
H
H
Cl
Cl
O
Cl
N
Cl
O
Cl
+
N
N
+
O
O
R2
N
N
O
R2
+
R2
+
H
H
N
O
N
O
Cl
Cl
Examples from the Table further support Mechanism B.
benzoin oxidation, but only dichloromethane worked well. This
reaction was slow likely due to poor solubility of the reagents.
Benzyl alcohol was smoothly oxidized to benzaldehyde in 60
minutes with no evidence10 of benzoic acid in the reaction
product.
Isoborneol and borneol (alcohols 6 and 7 in the Table) are
oxidized at different rates with pyridine as the added base
indicating a requirement for accessibility of the abstracted proton.
Substituting for pyridine (pKa 5.23) by the stronger base 4-
methylpyridine (4-picoline, pKa 5.96)11 increases the rate of
oxidation. Using an even stronger but sterically encumbered
base 2,4,6-trimethypyridine (collidine, pKa 7.45)11 decreases the
rate in all cases examined. The collidine experiment shows that
there is a strong steric factor in the reaction. By comparing the
cis/trans ratio of the starting material with the ratio after twenty
minutes of reaction using collidine, cis-4-t-butylcyclohexanol is
oxidized more rapidly than trans-4-t-butylcyclohexanol.10
Replacing collidine by the equally basic but sterically compact
tertiary amine 4-methylmorpholine (pKa 7.58)12 resulted in no
oxidation as there was a strong exothermic reaction of 4-
methylmorpholine with TCICA. This also works against
Mechanism A as a strong interaction with TCICA prevents
oxidation. It appears that abstraction of the hydrogen attached to
the alcohol carbon contributes substantially to the rate of
reaction. This is seen by comparing the time required for
complete oxidation of isoborneol and borneol using either
pyridine or collidine as the base. Isoborneol was always oxidized
in less time than borneol (typically, ⅓ the time), and gas
chromatographic analysis indicated that there were no side
reactions.
The additional products of the reaction, 1,3,5-
triazine-2,4,6(1H,3H,5H)-trione (isocyanuric acid) and
pyridinium chloride are solids that are filtered from the reaction
solution and could be recycled. Thus the oxidation of secondary
alcohols with TCICA and a pyridine base presents a rapid and
gentle procedure that provides high yields of clean products from
inexpensive starting materials.
Acknowledgments
We thank La Salle University for financial support. A
portion of this work was accomplished on a sabbatical provided
for the principal author. The nmr spectrometer used in this work
was donated by Merck.
References
(1) Arterburn, J. B. Tetrahedron 2001, 57,9765-9788.
(2) Tojo, G.; Fernandez, M. Oxidations of Alcohols to
Aldehydes and Ketones, Aguide to Current Common
Practice; Springer: Berlin, 2006; pp. 339-349.
(3) Mukawa, F., Nippon Kagaku Zasshi 1957, 78, 450-452.
(4) Hiegel, G. A., Nalbandy, M. Syntn. Commun. 1992, 22,
1589-1595.
(5) De Luca,L., Giacomelli,G., Masala, S., Porcheddu, A.
J. Org. Chem. 2003, 68, 4999-5001 and references
cited.
The range and selectivity of this oxidation is excellent.
Aliphatic reactants were oxidized in 20 minutes unless a steric
problem was present (borneol, menthol). Reactants having
aromatic rings close to the reaction site took longer with pyridine
as the base but were often complete in 20 minutes with 4-
methylpyridine as base. Oxidation of diols with one primary and
one secondary alcohol (2-ethylhexane-1,3-diol, 2-phenylethane-
1,2-diol, alcohols 4 and 11 in Table) caused only the secondary
alcohol to be oxidized. Benzoin was a special case (likely due to
poor solubility in ethyl acetate) but was smoothly oxidized under
appropriate conditions. Several solvents were tried for the
(6) Van Summeren, R. P., Romaniuk, A., IJpeij, E. G.,
Alsters, P. A. Catal. Sci. Technol.,2012, 2, 2052-2056.
(7) Tilstam, U.; Weinmann, H. Org. Proc. Res. Dev., 2002,
6, 384-393.