Efficient and selective aerobic alcohol oxidation catalyzed by copper(II)/2,2,6,6,-tetramethylpiperidine-1-oxyl at room temperature

Article abstract of DOI:10.1002/adsc.201000290

A simple and efficient copper(II)/2,2,6,6,-tetramethylpiperidine-1-oxyl (TEMPO)-catalyzed aerobic oxidation of both primary and secondary benzylic, allylic, and aliphatic alcohols to their corresponding aldehydes and ketones at room temperature using the copper(II) complex [Cu(μ-Cl)(Cl)(phen)] ₂ as the Cu(II) source is reported. The conversion of both electron-rich and electron-neutral benzyl alcohols is smooth and faster than those of electron-deficient ones. The chemoselectivity of a primary benzyl alcohol over the secondary alcohol is also observed. Alcohols regarded as difficult substrates for oxidation due to their coordinating ability with transition metal catalyst such as 4-(methylthio)benzyl alcohol and 3-pyridinemethanol are also oxidized easily. In addition, a lignin model alcohol is oxidized to the corresponding aldehyde in excellent yield. Conversions of benzylic and allylic alcohols are faster as compared to those of aliphatic alcohols in accordance with their Cα-H bond strengths. A plausible mechanism of the TEMPO-based catalytic cycle is proposed. Copyright

Full text of DOI:10.1002/adsc.201000290

FULL PAPERS
DOI: 10.1002/adsc.201000290
Efficient and Selective Aerobic Alcohol Oxidation Catalyzed
by Copper(II)/2,2,6,6,-Tetramethylpiperidine-1-oxyl at Room
Temperature
Md. Munkir Hossaina and Shin-Guang Shyua,*
a
Institute of Chemistry, Academia Sinica,Taipei, Taiwan 11529, Republic of China
Fax : (+886)-2-2783-1237; phone: 886-2-2789-8593; e-mail: sgshyu@chem.sinica.edu.tw
Received: April 14, 2010; Revised: September 24, 2010; Published online: November 17, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000290.
Abstract: A simple and efficient copper(II)/2,2,6,6,- with transition metal catalyst such as 4-(methylthio)-
tetramethylpiperidine-1-oxyl
(TEMPO)-catalyzed benzyl alcohol and 3-pyridinemethanol are also oxi-
aerobic oxidation of both primary and secondary dized easily. In addition, a lignin model alcohol is
benzylic, allylic, and aliphatic alcohols to their corre- oxidized to the corresponding aldehyde in excellent
sponding aldehydes and ketones at room tempera- yield. Conversions of benzylic and allylic alcohols
ture using the copper(II) complex [Cu
ACHTUNGTRENNUNG(phen)]2 as the Cu(II) source is reported. The con- in accordance with their Ca H bond strengths. A
version of both electron-rich and electron-neutral plausible mechanism of the TEMPO-based catalytic
benzyl alcohols is smooth and faster than those of cycle is proposed.
ACHTUNGERTN(NUNG m-Cl)(Cl)- are faster as compared to those of aliphatic alcohols
À
electron-deficient ones. The chemoselectivity of a
primary benzyl alcohol over the secondary alcohol is Keywords: aerobic oxidation; alcohols; catalysis;
also observed. Alcohols regarded as difficult sub- copper;
strates for oxidation due to their coordinating ability (TEMPO)
2,2,6,6,-tetramethylpiperidine-1-oxyl
Introduction
Of particular interest are the catalytic systems involv-
ing inexpensive transition metal compounds with less
Selective alcohol oxidation to the corresponding car- hazardous metals such as copper. In nature, copper
bonyl compounds is widely recognized as one of the enzymes are ubiquitous, and a few of them have been
fundamental transformations in organic synthesis.[1] involved in the binding of molecular oxygen for aero-
The catalytic conversion of primary alcohols to alde- bic oxidation transformations of natural products in a
hydes is important for the preparation of fine chemi- mild and highly selective way.[12] Copper complexes
cals.[2] There are numerous diverse methods that ac- are thus expected to be an efficient and selective cata-
complish this fundamental selective oxidation. Tradi- lysts for oxidative transformations.
tional stoichiometric oxidants (i.e., KMnO4, MnO2,
Recently the nitroxyl radical, 2,2,6,6, tetramethylpi-
CrO3, SeO2, Br2, etc.) are reported for this transfor- peridine-1-oxyl (TEMPO), has been extensively stud-
mation with considerable drawbacks such as high ied as a catalyst or catalyst component for alcohol
cost, toxicity, and production of large amounts of transformations with[8,13] and without[14] transition
waste. Moreover, the reactions are often performed in metals. The combination of TEMPO and copper ions
environmentally undesirable solvents; typically chlori- (i.e., a copper-TEMPO catalytic system) is expected
nated hydrocarbons.[3] Thus interest in developing an to be an efficient and selective catalytic system for
economic and environmental-friendly protocol is in- the aerobic oxidation of alcohols.[13a,c–r] Generally,
creased. In this regard, catalytic aerobic alcohol oxi- copper salts or in situ-generated copper complexes
dation in non-halide solvent is a highly desirable with nitrogen-containing ligands are used for alcohol ox-
system.
idation to the corresponding carbonyl compounds.[8,13a,c–r]
For catalytic aerobic alcohol oxidation, transition The alcohol oxidation reactions using well-defined
metals such as V,[4] Co,[5] Mn,[6] Fe,[7] Cu,[8] Mo,[9] copper complexes are less reported.[8b,c,f,i,13n,p,r] Herein,
Ru,[10] Pd,[11] Os,[7] Au[7] have been used as catalysts. we report the selective aerobic alcohol oxidation
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Table 1. Optimization of the reaction conditions for aerobic
oxidation of benzyl alcohol.
using the isolated copper complex [CuACTHNUTRGNEU(GN m-Cl)(Cl)-
ACHTUNGTRENNUNG(phen)]2 with TEMPO as the catalyst system at room
temperature and an easy and simple method for the
preparation of the complex in high yield. A possible
reaction mechanism is also highlighted.
Solvents
Base
TEMPO
Yield[a] [%]
Results and Discussion
acetonitrile
yes
no
yes
no
yes
no
yes
no
yes
no
yes
no
no
trace
The synthesis and structure of dimer [Cu
(phen)]2 were reported in the recent past.[15] A com-
plex with same composition [Cu(m-Cl)(Cl)(phen)]2
but of different structure was also synthesized under
non-hydrothermal conditions, and its DNA binding
behavior was studied.[16] Although the biological and
non-linear optical activities of the complexes with the
composition [CuACHTUNGTRENNUNG(m-Cl)(Cl)ACHTUNGTERN(NUGN phen)]2 were investigated,
their catalytic behavior was not examined.
The reported yields of the complexes using the hy-
drothermal technique are low and difficult for further
study. In order to evaluate the catalytic activity of
ACHTUNGTRENUN(NG m-Cl)(Cl)-
yes
yes
no
trace
99[b,c]
ACHTUNGTRENNUNG
U
ACHTUNGTRENNUNG
no reaction
trace
acetonitrile+water (1:1)
no
yes
yes
no
trace
99[b,c]
no reaction
trace
trace
water
no
yes
yes
no
25
no reaction
[a]
GC yields using 1,4-di-tert-butylbenzene as an internal
standard.
When air is used instead of O2, the conversion was 95%.
Same results were obtained using K2CO3 as a base.
[CuACHTUNGTRENNUNG(m-Cl)(Cl)ACHTUNGTRENNUNG(phen)]2, a direct reaction between cop-
[b]
[c]
per(II) chloride and phenanthroline was carried out.
Room temperature stirring of a dichloromethane so-
lution of equimolar amounts of CuCl2·2H2O and phe-
nanthroline overnight gave a green complex. Both el- selectivity towards oxidation of benzylic and allylic al-
À
emental analysis and single-crystal X-ray diffraction cohols is consistent with their weaker Ca H bond
study identified the green complex to be [Cu
A
Cl)(Cl)
(91%).
ACHTUNGTRENNUNG
The stability and solubility of 1 in water qualify this than those of the secondary alcohols (entries 9, 12,
complex to potentially be a good catalyst under aque- and 14) of the benzylic, allylic, and aliphatic systems.
ous conditions. We have optimized the conditions of This may be attributed to the steric hindrance of the
catalytic aerobic alcohol oxidations in different sol- a-substituents in secondary alcohols. The initial con-
vent systems using 1 and TEMPO as the catalyst version of aliphatic 1-octanol was satisfactory but the
system and benzyl alcohol as the model substrate. reaction slows down dramatically after 3 h, giving a
The results are summarized in Table 1.
final conversion of 57% (entry 13). Longer reaction
Both neat acetonitrile and the 1:1 mixture of aceto- time, up to 22 h, did not improve the conversion
nitrile and water are effective solvents in the benzyl yield. The instability of the oxoammonium ion in the
alcohol oxidation. Water alone was found to be un- presence of an aliphatic aldehyde and oxygen may de-
suitable. This may be due to the poor solubility of crease the catalytic activity as reported.[13a] Further-
benzyl alcohol in water. Both TEMPO and base are more, the conversions of electron-rich and electron-
essential for a successful conversion because the Cu neutral benzyl alcohols are faster and more efficient
complex alone is ineffective. Air can be used instead than those of electron-deficient ones (entries 1–5).
of oxygen with a slightly longer reaction time because Surprisingly, 4-(methylthio)benzyl alcohol and 3-pyri-
of the lower partial pressure of oxygen in air. Subse- dinemethanol, which are usually regarded as difficult
quently, the catalytic system was then applied to vari- substrates in most aerobic oxidations involving transi-
ous alcohols in acetonitrile as summarized in Table 2. tion metals due to their strong coordinating ability,
Various primary and secondary alcohols of benzylic, were also very smoothly converted into their corre-
allylic, and aliphatic types were successfully oxidized sponding aldehydes with high yields (entries 6 and 7).
to their corresponding carbonyl derivatives. Benzyl al- In addition, the lignin model compound could be se-
cohol is almost quantitatively and selectively convert- lectively oxidized into its corresponding aldehyde
ed to benzaldehyde (entry 1) in high yield. In general, with excellent conversion yield (entry 8). The conver-
the conversions of benzylic and allylic alcohols to the sion yields of both primary and secondary allylic alco-
corresponding carbonyl compounds were faster and hols are excellent (entries 10–12). A typical reaction
more efficient (entries 1–12), whereas the aliphatic al- involving a mixture of benzyl alcohol and 1-phenyl-
cohols reacted more slowly (entries 13 and 14). This
ACHTUNGTRENeNGNU thanol shows specificity of the copper(II)-TEMPO
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Efficient and Selective Aerobic Alcohol Oxidation
Table 2. Aerobic oxidation of alcohols into aldehydes and ketones.
Entry Alcohols
Products
Time in Conversion[a] GC yield[a] Yield[b] [%] (Conversion/GC yield)[f]
hour[f]
1
2
3
4
5
6
7
2 (3)
1.5 (2)
2 (3)
2 (3)
2 (4)
2 (3)
2 (3)
100
100
92
99
98
91
93
71[c]
91
95
83
95
89
91
65
87
85
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
95
ACHTUNGTRENNUNG
75
ACHTUNGTRENNUNG
94
ACHTUNGTRENNUNG
98
ACHTUNGTRENNUNG
8
9
2 (4)
5 (7)
89
99
87
97
83
ACHTUNGTRENNUNG
91
84
ACHTUNGTRENNUNG
10
11
2 (3)
2 (3)
93
97
91
ACHTUNGTRENNUNG
95[c,e]
–
ACHTUNGTRENNUNG
[d]
12
13
14
5 (6)
99
57
86
97
53
83
71
47
78
ACHTUNGTRENNUNG
3 (3)
ACHTUNGTRENNUNG
10 (15)
ACHTUNGTRENNUNG
15
2 (3)
92
8
91
7
73
2
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
[a]
The conversion and GC yield were measured by GC with an internal standard (1,4-tert-butylbenzene).
Isolated yield.
K2CO3 used as a base.
Unable to isolate pure poduct.
Decane as a GC internal standard.
Time, conversion, and GC yield included in the parentheses are from the alcohols oxidation reactions with less solvent
and base.
[b]
[c]
[d]
[e]
[f]
catalytic system towards primary alcohol because mum solvent and base (see Supporting Information),
92% of benzyl alcohol was converted into aldehyde, and then alcohol oxidation reactions were repeated
whereas only 8% of the 1-phenylethanol was oxidized and we tried to reach high conversion yield (~100%)
within 2 h (entry 15). This chemoselectivity, a charac- by increasing the reaction time over that of the initial
teristic of the natural copper protein galactose oxida- runs. The results are summarized in Table 2.
se,[8b,c,17] may be useful for selective oxidations of alco-
hol in synthetic organic chemistry when there are dif-
ferent alcoholic functions in the substrate. It was also Mechanism
noted that, after the end of the oxidation reaction,
the copper catalyst is still active because addition of In an investigation towards the mechanism for the
more equivalents of benzyl alcohol to the reaction copper(II)-TEMPO-catalyzed oxidation of alcohol to
mixture led the conversion to completion in 4 h. In aldehyde, Semmelhack[13a,18] first proposed that the
general, side products including formation of acids formation of an oxoammonium ion, generated by the
from further oxidation of aldehydes and ketones were oxidation of TEMPO, involves the abstraction of a b-
not observed. The possibility of over-oxidation may hydrogen forming an ionic transition state
A
be inhibited by TEMPO.[6b,c,13b,14i] The catalytic reac- (Figure 1). Later on, Sheldon et al.[13g] proposed a
tion conditions were further optimized using mini- mechanism based on copper-centred radical-mediated
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Md. Munkir Hossain and Shin-Guang Shyu
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Figure 1.
Scheme 1. Proposed catalytic cycle.
b-hydrogen abstraction via a transition state B
(Figure 1) during aerobic alcohol oxidation by the
CuBr
explained the failure of the secondary alcohol 1-phe- tion of hydroxylamine regenerates the oxoammonium
nylethanol to undergo oxidation in the CuBr2A(Bipy)- ion. The oxidation of hydroxylamine with oxoammo-
2ACHTUNGTRENNUNG(Bipy)-TEMPO catalytic system. These authors itself is reduced to hydroxylamine; successive oxida-
CTHUNGTRENNUNG
TEMPO catalytic system by the steric effect of the nium ion gives two nitroxyl radicals, which are again
methyl substituent on the a-carbon atom, which hin- oxidized by Cu(II) to two oxoammonium ions. Here,
dered the formation of B, and that is crucial for the Cu(II) is regenerated by the oxidation of Cu(I) with
À
C H abstraction from the alcohol by the coordinated primary oxidant oxygen producing water as a by-
TEMPO molecule. Moreover, in the case of primary product and thus completes the catalytic cycle.
alcohols, the second b-hydrogen atom can be bonded
As the isolation of reaction intermediates cannot
to the oxygen atom of TEMPOH and stabilizes the be achieved, it is difficult to ascertain the fate of the
radical intermediate C (Figue 1), which is not possible catalyst 1 during alcohol oxidation reactions in acce-
in secondary alcohols.[13g] Sheldon et al.[13h] also ap- tonitrile. Recently, electrospray ionization-mass spec-
plied the Semmelhack procedure[13a] (CuCl-TEMPO) trometry (ESI-MS) has been used as an effective
to the aerobic oxidation of a wider range of alcohol method for the characterization of reaction interme-
substrates and found out that benzylic and allylic al- diates.[13o,u,19] We have performed the ESI-MS in the
cohols were smoothly oxidized, and simple aliphatic following manner. Complex 1 is immersed in the ace-
alcohols were inactive.[13h] This trend is inconsistent tonitrile solution and stirred for 10 min under oxygen
with the well known oxoammonium ion mechanism bubbled conditions. The ESI-MS measurements in the
because oxoammonium ion can catalyze a wider positive-ion mode were then performed. Besides the
range of alcohols, including the facile oxidation of dominating peak at m/z=458, two moderate peaks at
simple aliphatic alcohols.[14c,e] The results obtained in m/z=773 and m/z=319 and two weak peaks at m/z=
our experiments favour the oxoammonium ion-medi- 423 and m/z=593 were obseved in the ESI-mass spec-
ated mechanism (which was also proposed for oxida- trum. According to the isotope distributions, these
tion of alcohols by other oxidants and TEMPO[14c,e]
because the catalytic system involves smooth oxida- [C36H24N6Cl3Cu2]+
tion of different kinds of alcohols including aliphatic (m/z=319),
[C24H16N4Cu]+
)
can be assigned as [C24H16N4ClCu]+ (m/z=458),
(m/z=773),
[C14H11N3ClCu]+
AHCTUNGTRENNGNU (m/z=423) and
ones (Table 2). The observation of
a
peak at [C24H16N4Cl3Cu2]+ (m/z=593), respectively (see Sup-
1630 cmÀ1 in the IR spectrum (see Supporting Infor- porting Information). After addition of K3PO4 and
mation) of the catalytic reaction mixture indicates the TEMPO, the peak intensities at m/z=593 and m/z=
formation of the oxoammmonium ion[14c] and further 319 are significantly reduced and the dominant peak
supports the above proposed mechanism.
at m/z=458 prevailed as before along with the mod-
The catalytic cycle is shown in Scheme 1. Initially, erate peaks at m/z=773 and m/z=423. After adding
the nitroxyl radical is oxidized to the oxoammonium benzyl alcohol into the system for an hour, the peak
ion by the Cu(II) complex; then the oxoammonium at m/z=423 with high intesitiy was observed. Thus, al-
ion serves as the catalytic oxidant and oxidizes the al- though a dimeric copper complex was used initially,
cohol substrates via a possible ionic transition state A monomeric copper species were formed during the al-
(Figure 1) to the corresponding carbonyl compounds. cohol oxidation in the basic acetonitrile solution.
During oxidation of alcohols, the oxoammonium ion However, the peaks corresponding to the
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Efficient and Selective Aerobic Alcohol Oxidation
formation of the complexes [Cu
[Cu(phen)(benzyl alcohol)], and
(TEMPO)(benzyl alcohol)] were not observed.[13o]
ACHUTGTNRNEUG(N Phen)ACHTUGNTRENNNUG
N
ACHTUNGTRENNUNG
N
a Cu catalytic system that alone can oxidize different
The present catalytic system is different with re- types of alcohols leading to the diverse aspects of al-
spect to its catalytic behaviour, in particular with cohol oxidation.
reagrd to secondary alcohol oxidation, from that of
the previously reported CuACTHNUTRGNEUGN(diimine) catalytic sys-
tems.[13g–i,n,k,o,u] This may be due to the difference in Experimental Section
their oxidation paths as in the present case where
oxoammonium ion mechanism has been favoured. To General Information
justify this pathway, we need to consider two points:
All chemicals were obtained from commercial sources and
(i) feasibility of oxoammonium ion formation via oxi-
dation of TEMPO by Cu(II) and (ii) stability of this
ion in the catalytic conditions of the alcohol oxidation
reactions. Electrochemical studies suggest that Cu(II)
can oxidize the nitroxyl into the corresponding nitoso-
nium species since a required potential (+0.4 V) for
that oxidation is much below the one reported for
the Cu(I)/Cu(II) couple (+0.7 V) in acetonitrile sol-
vent[13a,20] and such a type of oxidation by Cu(II) is
also reported.[20] With regards to stability in aquous
solutions, it has been observed that the oxoammoni-
um ions orignating from various nitroxyl radicals in-
cluding TEMPO are rather unstable in water, espe-
cially at alkaline pH.[13k,14e]
It is also well known that solvent as a reaction
medium has an important impact not only on reactivi-
ty and selectivity but also on sustainability.[13u,21] The
most commonly used solvent for nitrosonium ion oxi-
dations has been acetonitrile.[14c] Other solvents, such
as nitromethane, acetic anhydride, and tert-butyl alco-
hol have also been used.[14c] We carried out the alco-
hol oxidation in acetonitrile solvent with a weak base.
used without further purification. Decane, 4-chlorobenzyl al-
cohol, 4-methylbenzyl alcohol, 4-methoxybenzyl alcohol, 4-
nitrobenzyl alcohol, 3,4-dimethoxybenzyl alcohol, 1-phenyl
ethyl alcohol, 4-(methylthio)benzyl alcohol, trans-cinnamyl
alcohol, 3-penten-2-ol, phenanthroline, 2,2,6,6-tetramethylpi-
peridine-1-oxyl (TEMPO), and cuppric chloride dihydride
were purchased from Acros. 3-Pyridinemethanol was ob-
tained from TCI, and benzyl alcohol, 1-octanol, 2-octanol, 2-
buten-1-ol were purchased from Alfa Aesar. Flash chroma-
tography was performed using silica gel (MN 60, 230–400
mesh). The reactions were carried out under air or oxygen.
Gas chromatographic analyses were performed on an Agi-
lent 6890 instrument with an FID detector and an Aglient
30 mꢁ0.53 mmꢁ3.0 mm HP-1 capillary column. Infrared
spectra were recorded on a Perkin–Elmer 100 infrared spec-
trometer. NMR spectra were measured in CDCl3 on a
Bruker AV 400 MHz. High resulation ESI-MS were mea-
sured using a Waters LCT Premier XE with a dual ioniza-
tion ESCiꢂ in the Mass Spectrometry Facility in the Institute
of Chemistry, Academia Sinica. Leucine-enkephalin [M+
H]+ m/z=556.277 was used as a reference standard.
Synthesis of Complex [(phen)CuACTHNUTRGNEG(NU m-Cl)(Cl)]2
For the CuACHTUNGTRENNUNG(diimine)-TEMPO catalytic system, oxida-
Room temperature stirring of a dichloromethane solution
(75 mL) of CuCl2·2H2O (852 mg, 5.0 mmol) and phenan-
throline (991 mg, 5.0 mmol) overnight under air afforded
tion reactions were performed in aqueous
solution[13o,u] or acetonitrile/water (2/1, v/v) mixed
solvent[13g–i,n,k,14c] with a strong base. The oxoammium
ion may not be stable under such reaction condi-
tions,[13k,14c] and no alcohol oxidation was observed in
neat acetonitrile.[13g–i] These findings indicate that
both catalytic systems differ in their catalytic pathway,
and that for our system involves an oxoamminium
ion which is stable under the reaction conditions as
supported by the IR spectra and its broad reaction
scope including the facile oxidation of aliphatic alco-
hols.[14c,e]
the green crystalline complex [(phen)CuACTHNUTRGNEG(NU m-Cl)(Cl)]2; yield:
1431 mg (91%). The complex was characterized by single-
crystal X-ray diffraction and elemental analyses (anal. calcd.
for C24H16N4Cl4Cu2: C 45.80, H 2.56, N 8.90; found: C 45.70,
H 2.52, N 8.67).
Typical Procedure for the Oxidation
To
a solid mixture of [(phen)CuACHTUNTGERNUGN(m-Cl)(Cl)]2 (141 mg,
0.225 mmol), TEMPO (70 mg, 0.45 mmol), internal standard
1,4-di-tert-butylbenzene (190 mg, 1.0 mmol) or decane
142 mg, 1.0 mmol), and K3PO4 (955 mg, 4.5 mmol) or K2CO3
(622 mg, 4.5 mmol), 30 mL acetonitrile were added and the
mixture was stirred for 10 min at room temperature. Alco-
hol (9.0 mmol) was then added and stirring was continued
with oxygen bubbling. The color of the reaction mixture
turned from green to reddish orange. The products were an-
alyzed by GC. The reaction mixture was then portioned be-
tween diethyl ether (50 mL) and water (50 mL). The aque-
ous phase was extracted with diethyl ether (2ꢁ20 mL). The
combined organic extracts (90 mL) were washed successive-
ly with water (50 mL), 1M HCl (50 mL), and 50 mL of satu-
Conclusions
The copper(II)-TEMPO catalytic system reported
here is simple to prepare and easy to use for the effi-
cient aerobic oxidation of primary and secondary ben-
zylic, allylic, and aliphatic alcohols to their corre-
sponding aldehydes and ketones at room temperature.
The catalytic system is also unique as it succeeds to
oxidize different kinds of alcohols and possesses che- rated aqueous NaCl solution, dried over MgSO4, and then
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Md. Munkir Hossain and Shin-Guang Shyu
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concentrated under vacuum for purification. In the case of
3-pyridinecarboxaldehyde, the combined ether extracts
(90 mL) were washed only with water (50 mL) and dried
over MgSO4, and then concentrated under vacuum for pu-
rification.
For alcohol oxidation, reactions with less solvent and base
were carried out in a similar procedure as that of stated
above. Alcohol (9.0 mmol) and 477.5 mg, 2.25 mmol base in
20 mL accetonitrile were used in the reaction. The reaction
time, conversion, and GC yields are given in the parentheses
in the Table 2.
Benzaldehyde: Silica gel column chromatography
(hexane/dichloromethane=4:1) gave benzaldehyde as a col-
orless liquid; yield: 792 mg (83%). 1H NMR (CDCl3,
400 MHz): d=9.99 (s, 1H), 7.86–7.48 (m, 5H); 13C NMR
(CDCl3, 400 MHz): d=192.11, 136.17, 134.21, 129.48, 128.76.
4-Chlorobenzaldehyde: Silica gel column chromatography
(hexane/dichloromethane=1:1) gave 4-chlorbenzaldehyde
as a white solid; yield: 1202 mg (95%). 1H NMR (CDCl3,
400 MHz): d=9.92 (s, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.74 (d,
J=8.4 Hz, 2H); 13C NMR (CDCl3, 400 MHz): d=190.86,
140.89, 134.78, 130.93, 129.46.
Acetophenone: Silica gel column chromatography (di-
chloromethane) gave acetophenone as a colorless liquid;
1
yield: 984 mg (83%). H NMR (CDCl3, 400 MHz): d=7.88
(d, J=7.6 Hz 2H), 7.50–7.46 (m, 1H), 7.40–7.36 (m, 2H),
2.51 (s, 3H); 13C NMR (CDCl3, 400 MHz): d=198.11,
137.10, 133.10, 128.57, 128.29, 26.56.
trans-Cinnamaldehyde: Silica gel column chromatography
(ether/pentane=1:4) gave trans-cinnamaldehyde as a color-
less liquid; yield: 998 mg (84%). 1H NMR (CDCl3,
400 MHz): d=9.62 (d, J=8.0 Hz, 1H), 7.47–7.33 (m, 6H),
6.61 (m, 1H); 13C NMR (CDCl3, 400 MHz): d=193.46,
152.56, 133.84, 131.10, 128.93, 128.35.
3-Penten-2-one: Silica gel column chromatography (ether/
pentane=1:4) gave 3-penten-2-one as a colorless liquid;
1
yield: 538 mg (71%). H NMR (CDCl3, 400 MHz): d=6.69–
6.60 (m, 1H), 5.89 (d, J=15.6 1H), 2.03 (s, 3H), 1.71 (d, J=
6.8 Hz, 3H); 13C NMR (CDCl3, 400 MHz): d=198.29,
143.55, 132.74, 26.48, 18.03
Octanal: Silica gel column chromatography (dichlorome-
thane) gave octanal as a colorless liquid; yield: 542 mg
1
(47%). H NMR (CDCl3, 400 MHz): d=9.67 (s, 1H), 2.33 (t,
J=7.2 Hz, 2H), 1.57–1.51 (m, 2H), 1.22–1.19 (m, 8H), 0.79
(t, J=6.8 Hz, 3H); 13C NMR (CDCl3, 400 MHz): d=202.76,
43.95, 31.69, 29.18, 29.08, 22.64, 22.14, 14.06.
Methylbenzaldehyde: Silica gel column chromatography
(hexane/dichloromethane=1:4) gave 4-methylbenzaldehyde
1
2-Octanone: Silica gel column chromatography (dichloro-
methane) afforded 2-octanone as a colorless liquid; yield:
as a colorless liquid; yield: 961 mg (89%). H NMR (CDCl3,
400 MHz): d=9.91 (s, 1H), 7.72 (d, J=8.0 Hz, 2H), 7.27 (d,
J=7.6 Hz, 2H), 2.38 (s, 3H); 13C NMR (CDCl3, 400 MHz):
d=192.06, 145.63, 134.31, 129.92, 129.80, 21.94.
1
542 mg (78%). H NMR (CDCl3, 400 MHz): d=2.30 (t, J=
7.2 Hz, 2H), 2.07 (s, 3H), 1.46–1.16 (m, 8H), 0.76 (t, J=
6.0 Hz, 3H); 13C NMR (CDCl3, 400 MHz): d=209.10, 43.74,
31.59, 29.75, 28.84, 23.81, 22.48, 13.97.
4-Methoxybenzaldehyde: Silica gel column chromatogra-
phy (hexane/dichloromethane=1:1) gave 4-methoxybenzal-
1
dehyde as a colorless liquid; yield: 1115 mg (91%). H NMR
Oxidation of Benzaldehyde and sec-Phenylethyl
Alcohol
(CDCl3, 400 MHz): d=9.91 (s, 1H), 7.86 (d, J=8.0 Hz, 2H),
7.03 (d, J=8.0 Hz, 2H), 3.91 (s, 3H); 13C NMR (CDCl3,
400 MHz): d=189.15, 162.91, 130.31, 128.25, 112.68, 54.07.
4-Nitrobenzaldehyde: Potassium carbonate was used as
the base in the reaction. Silica gel column chromatography
(hexane/dichloromethane=1:4) gave 4-nitrobenzaldehyde as
a white solid; yield: 884 mg (65%). 1H NMR (CDCl3,
400 MHz): d=10.12 (s, 1H), 8.34 (d, J=8.8 Hz, 2H), 8.04
(d, J=8.8 Hz, 2H); 13C NMR (CDCl3, 400 MHz): d=190.52,
151.23, 140.20, 130.62, 124.42.
In a typical reaction, to a solid mixture of [(phen)Cu
ACHTUNGTRENNUNG(m-
Cl)(Cl)]2 (142 mg, 0.225 mmol), TEMPO (70 mg,
0.45 mmol), internal standard 1,4-di-tert-butylbenzene
(190 mg, 1.0 mmol) and K3PO4 (955 mg, 4.5 mmol), 30 mL
acetonitrile were added and the mixture was stirred for
10 min at room temperature. Benzyl alcohol (487 mg,
4.5 mmol) and sec-phenylethyl alcohol (550 mg, 4.5 mmol)
were then added and stirring was continued with oxygen
bubbling. The extraction of the reaction mixture was done
as above. The silica gel column chromatography (ether/pen-
tane=0.5:9.5) afforded benzaldehyde and acetophenone as
colorless liquid in yields of 73% (349 mg) and 2% (11 mg),
respectively. 1H NMR and 13C NMR of isolated benzalde-
hyde and acetophenone are similar to those reported above.
4-(Methylthio)benzaldehyde: Silica gel column chroma-
tography (hexane/dichloromethane=1:4) gave 4-(methyl-
thio)benzaldehyde as a colorless liquid; yield: 1192 mg
1
(87%). H NMR (CDCl3, 400 MHz): d=9.81 (s, 1H), 7.65
(d, J=8.4 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 2.41 (s, 3H);
13C NMR (CDCl3, 400 MHz): d=191.07, 147.83, 132.83,
129.85, 125.06, 14.53.
3-Pyridinecarboxaldehyde: Silica gel column chromatog-
raphy (dichloromethane) gave 3-pyridinecarboxaldehyde as
a colorless liquid; yield: 814 mg (85%). 1H NMR (CDCl3,
400 MHz): d=10.01 (s, 1H), 8.97 (s, 1H), 8.73 (d, J=4.8 Hz, Acknowledgements
1H), 8.06 (d, J=8.0 Hz, 1H), 7.40–7.37 (m, 1H); 13C NMR
(CDCl3, 400 MHz): d=189.91, 153.54, 150.75, 134.77, 130.27,
123.03.
The work was financially supported by the National Science
Council of the Republic of China and Academia Sinica.
3,4-Dimethoxybenzaldehyde: Silica gel column chroma-
tography (hexane/dichloromethane=0.5:9.5) gave 3,4-dime-
thoxybenzaldehyde as a white solid; yield: 1243 mg (83%).
1H NMR (CDCl3, 400 MHz): d=9.70 (s, 1H), 7.32–7.24 (m,
2H), 6.84 (d, J=8.0 Hz, 1H), 3.81 (d, 6H); 13C NMR
(CDCl3, 400 MHz): d=190.71, 154.36, 149.49, 130.02, 126.66,
110.34, 108.86, 56.03, 55.84.
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