3
of alcohol 1a catalyzed by TEMPO or various 4-substituted
,2,6,6-tetramethyl-1-oxyls 4a-c revealed that the structure of the
(ESI, Table S05). Interestingly, the formation of dimeric esters
as major products was recently described in the TEMPO/CaCl
catalyzed oxidation of primary alcohols with oxone in the
presence of water; however, this oxidation system was quite
different from the system described here.
2
2
-
nitroxide had no significant effect on the reaction rate or
selectivity (ESI, Table S02). Therefore, 4-acetylamino-2,2,6,6-
35
3
1
tetramethylpiperidine-1-oxyl (4a), a low-cost, readily accessible
TEMPO derivative, was applied as the catalyst in further
experiments.
Figure 1. Structures of alcohols 1a-c.
The effect of the pH of the aqueous solution on the oxidation
of alcohols 1a,c was also studied (ESI, Table S03). In agreement
9
with the literature data for nitroxide-catalyzed alcohol oxidation,
high conversions were observed in a basic medium (aq. NaHCO
or Na CO ). At pH ~5.6, the reaction rates and selectivities were
low. When using Na CO solution (pH ~11.3), high
conversions of both alcohols 1a,c were attained; however, the
selectivity for the oxidation of 1c was low. Only the NaHCO
solution (pH ~8.7) provided appropriate rates and selectivities for
the oxidation reactions of both alcohols 1a,c. Therefore, NaHCO
3
2
3
a
2
3
2
Scheme 3. Oxidation of alcohols 1a-z with I catalyzed by compound 4a
3
in the absence of a pyridine co-catalyst (for details, see ESI, Table S05; for
the structures of R and Rʹ, see Table 1).
3
was selected as a mild inorganic base for the aqueous phase of
the system.
Therefore, despite some similarities to stoichiometric
7
,10
A molar ratio of alcohol:I
2
:4a = 1:2:0.05 was selected as a
oxidation reactions with oxoammonium salts,
catalyzed oxidation of alcohols with iodine in CH
the nitroxide-
Cl /NaHCO
starting point for further investigations based on comparative
experiments for the oxidations of alcohols 1a,c (see ESI, Table
S04 for results and further discussion).
2
2
3
(aq.) differs in terms of the rate and selectivity compared to the
majority of nitroxide-catalyzed oxidation reactions in two-phase
9
,18,22,32,36
systems.
From the results described above, it became
The oxidation of several primary and secondary alcohols with
iodine catalyzed by nitroxide 4a in the absence of a pyridine co-
catalyst revealed that the features of the reaction were similar to
non-catalytic stoichiometric oxidations of alcohols with
apparent that additional provisions were needed to enhance the
oxidation rate and selectivity, particularly in the case of primary
aliphatic alcohols. Therefore, catalysis with various pyridines
was investigated.
7
,10
oxoammonium salts (Scheme 3; ESI, Table S05).
Thus,
sterically unhindered benzyl alcohols and secondary aliphatic
alcohols were oxidized at reasonable rates, while primary
aliphatic alcohols required prolonged reaction times. Within the
range of homologs of linear primary aliphatic alcohols, the rate of
oxidation decreased successively with increasing hydrocarbon
chain length. Interestingly, these results differ sufficiently from
the results of analogous nitroxide-catalyzed oxidation reactions
We studied the effects of catalytic amounts of pyridine 6a and
alkyl-substituted pyridines 6b-d on the oxidation reactions of
various alcohols (Scheme 4; ESI, Table S07). It was revealed that
the addition of compounds 6a-d accelerated the oxidation
sufficiently compared to experiments without the addition of the
pyridine, in particular for the oxidation of primary aliphatic
alcohols 1a,j. However, the selectivity for the reactions of
alcohols 1a,j was highly susceptible to the structure of the co-
catalyst: unsubstituted pyridine 6a afforded predominantly
dimeric esters 7a,j, while substituted pyridines 6b-d provided the
corresponding aldehydes 2a,j as the major products (Scheme 4).
The highest yields of aldehydes were observed in the presence of
2,6-dimethylpyridine (lutidine, 6c) and, in particular, 2,4,6-
trimethylpyridine (collidine, 6d).
of alcohols with bleach (NaOCl) in a two-phase CH
aq.) system, for which the oxidation of primary alcohols
proceeded with higher rates than the oxidation of secondary
2 2 3
Cl /NaHCO
(
2
2,32
ones.
rates for the oxidation reaction of all types of alcohols;
Bleach oxidation provided sufficiently higher overall
2
2,23
,23
9
however, the formation of various by-products was reported.
Surprisingly, in the nitroxide-catalyzed oxidation of primary
aliphatic alcohols with iodine, we observed sufficiently high
yields of dimeric esters 7 in molar ratios of 7:2 up to 0.7:1
The observed selectivities for the oxidation of primary
aliphatic alcohols in the presence of pyridines 6a-d (ESI, Table
S07) were in agreement with the reported data regarding the
effects of the structures of pyridine bases on the selectivities for
the stoichiometric oxidation of alcohols using oxoammonium
salts: unsubstituted pyridine promotes the formation of dimeric
(
Scheme 3; ESI, Table S05). These results differ from the
stoichiometric oxidation of primary aliphatic alcohols with
oxoammonium salts, for which the formation of dimeric esters
7
,10,33
was detected only in minor yields (3-5%).
The formation of
12
esters, while 2,6-disubstituted pyridines produce aldehydes. The
dimeric esters 7 in relatively high yields prompted us to assume
that the non-catalytic oxidation of the alcohol with iodine has a
considerable contribution to the overall reaction. For example,
the oxidative esterification of alcohols with iodine is a well-
reaction rates reflected by the overall conversions correlate with
the basicities of compounds 6a-d and were highest in the
presence of collidine 6d (ESI, Table S07). Once again, these
observations agree with the relative energies calculated for the H-
bonded complexes between the oxoammonium cations, alcohols
and various pyridine bases, which have been proposed as
transition states (TS-1) in the pyridine-base catalyzed oxidation
3
4
known reaction. However, experiments regarding the oxidation
of various alcohols with iodine in a two-phase CH Cl /NaHCO
aq.) system revealed, in the absence of the nitroxide, that the
2
2
3
(
oxidation proceeds slowly and that the yields of carbonyl
compounds are 5-10 times lower (ESI, Table S06) in comparison
with the nitroxide-catalyzed oxidation under the same conditions
12
of alcohols to aldehydes or ketones (Fig. 2). Therefore, the most
likely mechanism for the reaction is analogous to the recently
described mechanism for the stoichiometric oxidation of alcohols