2518
H.-B. Ji et al. / Tetrahedron Letters 46 (2005) 2517–2520
using NaOCl as an oxidant with water as the only sol-
vent (Scheme 1). These reactions do not need any other
additives.
underwent smooth oxidation (entries 2–4). Commonly,
the existence of electron donating group such as
–OCH group favours alcohols oxidation, however
3
6
,7
the existence of –OCH group lowered the reaction rate,
3
Firstly, various oxidants such as molecular oxygen, air,
hydrogen peroxide and NaOCl were subject to benzyl
alcohol oxidation, and the result is shown in Table 1.
indicating that the space configuration of guest mole-
cules is more important for smooth conversion than
the influence from electron effect in the present catalytic
system (entry 3). This could be further supported by the
fact that the heteroaromatic primary alcohol such as 2-
pyridinemethanol could be converted to the correspond-
ing aldehyde with the similar reaction rate as benzyl
alcohol oxidation (entry 4). The length between benzene
ring and –OH group could significantly influence the
oxidation rate, since cinnamyl alcohol reacted for 4 h till
the completion of conversion (entry 1).
It could be concluded that neither weak oxidants such as
O or air nor moderate oxidant such as H O could be
2
2
2
used as effective oxidants towards benzyl alcohol with
b-cyclodextrin (entries 2–4). The addition of strong oxi-
dant NaClO significantly prompted the oxidation, and
complete conversion from benzyl alcohol to benzalde-
hyde could be achieved within 1 h without the formation
of by-products such as benzoic acid (entry 5). The exis-
tence of b-cyclodextrin is crucial because nearly no pro-
duct was formed without the addition of b-cyclodextrin.
It should be noted that b-cyclodextrin is stable under
the present reaction system. Although seven primary
hydroxyls and fourteen secondary hydroxyls exist in b-
cyclodextrin, the recovered b-cyclodextrin gave identical
IR spectra to the fresh one after one reaction. The fact
that the recovered b-cyclodextrin could be reused under
the same reaction condition, which will be discussed
later, also supported that b-cyclodextrin was unchanged.
The existence of other groups on the carbon bonded to
the –OH group could make the oxidation hardly occur.
For example, the oxidation of benzylic secondary alco-
hols could be completely retarded (entries 5–6), further
indicating the importance of space configuration. As
8
for the substrate 2-adamantanol, Liu and coauthors re-
ported that 2-adamantanol afforded very stable complex
with complex stability constant of 13,900, indicating
that L-Trp-b-cyclodextrin could recognize the minor dif-
ference in substitution pattern. The formation of a
hydrogen bond with the cyclodextrinÕs secondary
hydroxyls is more favourable for the adamantanolÕs hy-
droxyl group at the 2-position. This result presents that
host–guest complex between b-cyclodextrin and 2-ada-
mantanol possesses a more rigid structure, making the
hydroxyl group in 2-adamantanol hardly to be activated
and converted. This might account for the lack of oxida-
tion for 2-adamantanol (entry 7). The oxidation of 2-
octanol and 1-octanol for 24 h hardly gave any prod-
ucts, with starting material recovered (entries 8–9). This
result is comparable to the deprotection of 2-heptyl-1,3-
dioxolane catalyzed by b-cyclodextrin, where the com-
plexation between long chain aliphatic alcohol and
On the basis of the smooth oxidation of benzyl alcohol
with NaOCl, different reaction conditions including the
amount of NaOCl, the amount of b-cyclodextrin and
reaction temperature were investigated. As a result,
1
5
mmol of b-cyclodextrin, 5 mL of NaOCl (10%) and
0 ꢁC were chosen as a suitable reaction condition for
oxidation of alcohols.
In view of the efficient oxidation of benzyl alcohol, the
oxidation for various other alcohols was investigated
and the results are shown in Table 2.
9
It is known that b-cyclodextrin and substrates can form
host–guest complex. This complexation depends on the
size, shape and hydrophobicity of the guest molecule.
In the present research, benzylic primary alcohols
b-cyclodextrin might be hardly formed.
Unlike the aromatic primary alcohols or other second-
ary alcohols, cyclohexanol exhibited some reactivity to-
wards the oxidation (entry 10). The bulk of the
cyclohexyl group, with chair and boat conformations
occupying more space than an aromatic group, might
explain the low reactivity towards oxidation. The other
possible reason should attribute to the inactive hydroxyl
group in virtue of the absence of electron cloud
conjugation.
β
-
cyclodextrin
R
OH
R
O
o
NaOCl, H O, 50 C
2
Scheme 1.
The formation of aldehydes might occur through SN1
mechanism. Firstly, a b-cyclodextrin inclusion complex
between b-cyclodextrin and substrate was formed in
a
Table 1. Benzyl alcohol oxidation by various oxidants
Entry
Oxidant
Ar
Conv. (%)
Yield (%)
1
0
situ, followed by the formation of carbonium ion. This
1
2
3
4
5
<1
3
<1
3
À
carbonium ion was then attacked by ClO anion on car-
bon atom. Further elimination of HCl gave the corre-
sponding aldehydes (Fig. 1).
O
2
Air
3
3
30% H
2
O
2
(5 mL)
6
6
10% NaClO (5 mL)
10% NaClO (5 mL)
>99
3
>99
3
b
6
It should be noted that the existence of hydrogen bond
derived from H O influenced benzyl alcohol oxidation
a
Reaction conditions: b-cyclodextrin (1 mmol), benzyl alcohol
1 mmol), H
O (25 mL), 1 h, 50 ꢁC.
Blank experiment, without addition of b-cyclodextrin.
2
(
2
dramatically. The influence of other organic solvents
was given as in Scheme 2.
b