Organic Solvent- and Halide-Free Oxidation of Alcohols with Aqueous Hydrogen Peroxide

Full text of DOI:10.1021/ja973412p

12386
J. Am. Chem. Soc. 1997, 119, 12386-12387
Table 1. Oxidation of Secondary Alcohols with Aqueous
Organic Solvent- and Halide-Free Oxidation of
Alcohols with Aqueous Hydrogen Peroxide
Hydrogen Peroxidea
Kazuhiko Sato, Masao Aoki, Junko Takagi, and
Ryoji Noyori*
Department of Chemistry and Molecular
Chirality Research Unit, Nagoya UniVersity
Chikusa, Nagoya 464-01, Japan
ReceiVed September 30, 1997
The increasing demand for environment-conscious chemical
processes has impelled us to explore truly efficient oxidation
methods using aqueous H2O2, an ideal oxidant in this context.1
Although a number of procedures for alcohol oxidation using
H2O2 and in situ-generated or preformed metal complexes have
been reported,2,3 they all remain to be improved for application
to practical organic synthesis. We here describe the no-solvent
oxidation of primary and secondary alcohols under entirely
halide-free conditions.4 This method is high-yielding, clean,
safe, operationally simple, and cost-effective and therefore meets
with the requirements of contemporary organic synthesis.
Simple secondary alcohols can be converted cleanly to
ketones under organic/aqueous biphasic conditions using 3-30%
H2O2 in the presence of a tungsten catalyst and a phase-transfer
catalyst (PTC) (eq 1). For example, when a mixture of 2-octanol
a Unless otherwise stated, reaction was run using alcohol and 30%
H2O2 in a 1:1.1 molar ratio with stirring at 1000 rpm at 90 °C for 4 h.
PTC ) [CH3(n-C8H17)3N]HSO4. b Isolated by distillation. c Reaction
with 3% H2O2. d A 1:1 mixture of the cis and trans isomer. e Toluene
(100 mL) was used as solvent. f Reaction for 1 h.
W-catalyzed conditions, the oxidation requires only 1.1 molar
amounts of H2O2 per alcohol to obtain a satisfactory yield. Rapid
stirring is necessary to facilitate the biphasic reaction. Oxidation
of 2-octanol (100 g) using 3% H2O2 (958 g) occurs equally
well, giving 2-octanone in 95% yield (93.0 g). This procedure
may or may not be advantageous from a practical point of view,
because the content of active oxygen is lower than with 30%
H2O2.
(100 g), 30% H2O2 (96 g), Na2WO4‚2H2O (0.5 g),5 and [CH3-
(n-C8H17)3N]HSO4 (0.7 g)1 (500:550:1:1 mol ratio) placed in a
500-mL, round-bottomed flask was stirred at 1000 rpm with a
magnetic stirrer at 90 °C for 4 h, 2-octanone was produced in
97% yield (GLC analysis). Separation of the organic layer was
followed by washing with 100 mL of saturated aqueous Na2S2O3
and distillation (173 °C) to give a pure product (93.9 g, 95%
yield). The oxidation produced little waste. The water phase
of the reaction mixture, combined with the distillation residue,
can be reused with renewed PTC and 30% H2O2, giving 86
and 92% yield in the second and third runs, respectively. To
obtain an acceptable yield and rate while avoiding any potential
complications, reaction at 90 °C is recommended.6 Since
unproductive decomposition of H2O2 is negligible under such
This reaction system is entirely free from inorganic and
organic halides. The synthetic efficiency compares favorably
with existing methods that largely use quaternary ammonium
halides and chlorohydrocarbon solvents.2 Use of a lipophilic
quaternary ammonium hydrogensulfate as PTC is crucial for
high reactivity, probably due to the sufficient acidity. The
maximum rate was obtained by reaction at an initial pH of 2.
[CH3(n-C8H17)3N]Cl and [CH3(n-C8H17)3N]2SO4 were much less
reactive, giving 11 and 18% yield, respectively (1% yield
without PTC). The turnover number (TON) of the 2-octanol
oxidation, as defined as mols of product per mol of W,
approached 77 700, when oxidation was performed with an
alcohol:30% H2O2:W:PTC ratio of 200 000:300 000:1:100 (40%
yield). This TON value is two orders of magnitude higher than
any previously reported H2O2 oxidation.7 Venturello2f reported
that his no-solvent oxidation of 2-hexanol with 40% H2O2 and
isolated [CH3(n-C8H17)3N]3PO4[W(O)(O2)2]4 gave 2-hexanone
where TON ) 48.3/W in 96% (or 130/W and 18% in
benzene2g). Under our new conditions, 1-phenylethanol was
oxidized with an even higher TON, 179 000 (alcohol:W )
400 000:1, 45% yield).
The reaction does not normally use an organic solvent but,
if necessary, is achievable using toluene as solvent with a
crystalline alcohol, for example. Table 1 lists some examples
of 100 g-scale reactions. Oxidation of 2-ethyl-1,3-hexanediol
selectively gave 2-ethyl-1-hydroxy-3-hexanone, because the
second oxidation was slowed by the presence of the electrone-
gative keto group. Using this method, cis- and trans-4-tert-
butylcyclohexanol are oxidized at equal rates.9 In order to test
the tolerance of functional groups and also to confirm the
(1) (a) Sato, K.; Aoki, M.; Ogawa, M.; Hashimoto, T.; Noyori, R. J.
Org. Chem. 1996, 61, 8310-8311. (b) Sato, K.; Aoki, M.; Ogawa, M.;
Hashimoto, T.; Panyella, D.; Noyori, R. Bull. Chem. Soc. Jpn. 1997, 70,
905-915.
(2) For selected examples, see: (a) Jacobson, S. E.; Muccigrosso, D.
A.; Mares, F. J. Org. Chem. 1979, 44, 921-924. (b) Bortolini, O.; Conte,
V.; Furia, F.; Modena, G. J. Org. Chem. 1986, 51, 2661-2663. (c) Barak,
G.; Dakka, J.; Sasson, Y. J. Org. Chem. 1988, 53, 3553-3555. (d) Ishii,
Y.; Yamawaki, K.; Ura, T.; Yamada, H.; Yoshida, T.; Ogawa, M. J. Org.
Chem. 1988, 53, 3587-3593. (e) Zennaro, R.; Pinna, F.; Strukul, G.;
Arzoumanian, H. J. Mol. Catal. 1991, 70, 269-275. (f) Venturello, C.;
Gambaro, M. J. Org. Chem. 1991, 56, 5924-5931. (g) Dengel, A. C.;
Griffith, W. P.; Parkin, B. C. J. Chem. Soc., Dalton Trans. 1993, 2683-
2688. (h) Neumann, R.; Gara, M. J. Am. Chem. Soc. 1995, 117, 5066-
5074. (i) Arends, I. W. C. E.; Sheldon, R. A.; Wallau, M.; Schuchardt, U.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1144-1163.
(3) Catalytic oxidation of alcohols using other oxidants: (a) Sheldon,
R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic Compounds;
Academic: New York, 1981. (b) Griffith, W. P.; Ley, S. V. Aldrich. Acta
1990, 23, 13-19.
(4) Reviews on oxidation with widely used Cr-based reagents: (a) House,
H. O. Modern Synthetic Reactions, 2nd ed.; Benjamin: Menlo Park, 1972;
pp 257-291. (b) Cainelli, G.; Cardillo, G. Chromium Oxidations in Organic
Chemistry; Springer: New York, 1984. (c) Rao, A. S. In ComprehensiVe
Organic Synthesis; Trost, B. M., Fleming, I., Ley, S. V., Eds.; Pergamon:
Oxford, 1991; Vol. 7, pp 251-289.
(7) The highest reported value is 513, obtained with a large excess of
H2O2 and a RuCl3-[(CH3)2(n-C10H21)2N]Br catalyst system in CH2Cl2.2c
The best record with a W-based catalyst was 193/W atom in 1,2-
dichloroethane.2h
(5) Available from Aldrich at $15.10/5 g.
(6) Oxidation of 2-octanol at 60 and 30 °C for 16 h under otherwise
identical conditions gave the ketone in 57 and 7% yield, respectively.
S0002-7863(97)03412-4 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
J. Am. Chem. Soc., Vol. 119, No. 50, 1997 12387
Table 2. Oxidation of Primary Alcohols with Aqueous Hydrogen
Peroxidea
conversion. Interestingly, the initial rate of the alcohol oxidation
is enhanced by decreasing the H2O2 concentration. Under the
new conditions of alcohol oxidation using 5% H2O2, 2-octanol
is much more reactive than simple olefins. Relative rates (2-
octanol ) 1.0; substrate:H2O2:W:PTC ) 500:500:1:1, toluene,
110 °C, 1000 rpm) are 1-octene (0.036), (E)-3-octene (0.10),
(Z)-3-octene (0.15), 2-methyl-1-undecene (1,1-disubstituted ole-
fin, 0.094), 2-methyl-2-decene (trisubstituted olefin, 0.13), and
3,4-diethyl-3-hexene (tetrasubstituted olefin, 0.11). Olefinic
bonds in allylic alcohols are particularly reactive to epoxidation.1
1-Dodecen-3-ol, an allylic alcohol with a terminal olefinic bond,
was converted to the desired 1-dodecen-3-one in 80% yield (eq
3), contaminated with 1,2-epoxydodecan-3-ol (14%) and 1,2-
a Unless otherwise stated, reaction was run using alcohol and 30%
H2O2 in a 1:2.5 molar ratio with stirring at 1000 rpm at 90 °C for 4 h.
PTC ) [CH3(n-C8H17)3N]HSO4. b Isolated by distillation. c Isolated by
recrystallization. d Reaction using alcohol and 30% H2O2 in a 1:1 molar
ratio. Benzoic acid was produced in <3% yield.
catalytic activity in the presence of coordinative compounds,
2-octanol was oxidized in toluene containing an equimolar
amount of ethyl decanoate, ethyl benzoate, di-n-octyl ether, 1,2-
epoxydodecane, 2-methylcyclohexanone, or nonanenitrile. In
fact 2-octanone was obtained without problems in >92% yield,
while the latter compound was recovered in >95% yield.
Addition of 1 molar amount of butyramide, however, retarded
the reaction significantly, giving 2-octanone in a mere 18%
yield.
epoxydodecan-3-one (4%) (substrate:30% H2O2:W:PTC ) 500:
750:1:1, 90 °C, 3 h).12 On the other hand, 2-methyl-2-undecen-
4-ol possessing a trisubstituted CdC bond underwent selective
epoxidation (100% yield).
Primary alcohols are 4-5 times less reactive than secondary
ones. Significantly, however, they can be oxidized directly to
carboxylic acids (eq 4). Table 2 gives some examples. When
A major concern in H2O2 oxidation is the alcohol/olefin
chemoselectivity.1,2,8 This biphasic oxidation was initially
developed for olefin epoxidation1 but with an (aminomethyl)-
phosphonic acid additive for high selectivity.10 Now, the
removal of this additive has been found to significantly increase
the rate and selectivity of alcohol oxidation. Oxidation of 11-
dodecen-2-ol using 30% H2O2 with alcohol:H2O2:W:PTC )
500:750:1:1 (no solvent, 90 °C, 3 h, 1000 rpm) selectively
afforded 11-dodecen-2-one (97% yield) with a little undesired
11,12-epoxydodecan-2-one (0.4%) (eq 2).11 In a similar manner,
reaction of 5-cyclohexadecenol (E:Z ) 2:1) with 5% H2O2 in
toluene gave 5-cyclohexadecenone with 98% selectivity at 100%
a mixture of 1-octanol (100 g), 30% H2O2 (218 g), Na2-
WO4‚2H2O (5 g), and [CH3(n-C8H17)3N]HSO4 (7 g) (50:125:
1:1 mol ratio) was heated at 90 °C for 4 h with stirring at 1000
rpm, octanoic acid (96.5 g) was obtained in 87% isolated yield
after distillation. n-Octyl octanoate, a frequently obtainable
dimeric ester, was produced in only 2% yield. Reaction with
an alcohol:W ratio of 20 000:1 led to a TON as high as 3000
(15% yield).13 Oxidation obviously proceeds by way of octanal,
where the second oxidation via its hydrate is fast as a result of
the acidic aqueous conditions. Reaction of octanal with 30%
H2O2 in the presence of the W catalyst (aldehyde:H2O2:W:PTC
) 50:75:1:1, 90 °C, 2 h) afforded octanoic acid in 84% yield.
â-Branched primary alcohols are oxidized to carboxylic acids
in a fair yield. Notably, benzyl alcohol is selectively convertible
to benzaldehyde by using 1 molar equiv of H2O2.
(8) Activated MnO2, pyridinium dichromate (PDC), and CrO2 are used
as stoichiometric agents for selective oxidation of allylic alcohols. See: (a)
Fatiadi, A. J. Synthesis 1976, 65-104 and 133-167. (b) Corey, E. J.;
Schmidt, G. Tetrahedron Lett. 1979, 399-402. (c) Lee, R. A.; Donald, D.
S. Tetrahedron Lett. 1997, 38, 3857-3860. See, also: (d) Rao, A. S. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Ley, S. V.,
Eds.; Pergamon: Oxford, 1991; Vol. 7, pp 305-327.
(9) Chromic acid in acetic acid oxidizes the cis alcohol three times faster
than the trans isomer. See: Eliel, E. L.; Schroeter, S. H.; Brett, T. J.; Biros,
F. J.; Richer, J.-C. J. Am. Chem. Soc. 1966, 88, 3327-3334.
(10) For an excellent epoxidation procedure using H2O2, see: Rudolph,
J.; Reddy, K. L.; Chiang, J. P.; Sharpless, K. B. J. Am. Chem. Soc. 1997,
119, 6189-6190.
Acknowledgment. This work was aided by the Ministry of
Education, Science, Sports and Culture of Japan (No. 07CE2004).
Supporting Information Available: Experimental procedures for
(11) Reaction under the standard epoxidation conditions (alcohol:H2O2:
W:PTC:NH2CH2PO3H2 ) 100:110:2:1:1)1 gave a mixture of the enone
(39%), epoxy ketone (38%), and epoxy alcohol (2%).
1
the oxidation and H- and 13C-NMR data of the products (11 pages).
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(12) A decrease in the H2O2 concentration did not improve chemo-
selectivity.
(13) Oxidation with a Ru-based catalyst in CH2Cl2 gave a TON of 363.2c
JA973412P