Highly efficient use of NaOCI in the Ru-catalysed oxidation of aliphatic ethers to esters

Article abstract of DOI:10.1039/b109390h

The selectivity of α-oxidation of ethers to esters via RuNaOCI can be dramatically improved by pH control, at high substrate to catalyst ratios using a stoichiometric amount of hypochlorite in biphasic media at room temperature.

Full text of DOI:10.1039/b109390h

Highly efficient use of NaOCl in the Ru-catalysed oxidation of aliphatic
ethers to esters
Luca Gonsalvi, Isabel W. C. E. Arends and Roger A. Sheldon*
Laboratory for Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136 2628 BL.
Delft, The Netherlands. E-mail: R.A.Sheldon@tnw.tudelft.nl; Fax: +31 15 2781415; Tel: +31 15 2782675
Received (in Cambridge, UK) 16th October 2001, Accepted 5th December 2001
First published as an Advance Article on the web 7th January 2002
The selectivity of a-oxidation of ethers to esters via Ru–
NaOCl can be dramatically improved by pH control, at high
substrate to catalyst ratios using a stoichiometric amount of
hypochlorite in biphasic media at room temperature.
room temperature for 3 h, during which no further conversion
was observed and the pH stayed in the acidic region. The
addition of another aliquot of NaOCl (10 mmol) caused the
precipitate to dissolve and led to complete conversion and a
final selectivity of 74% to the ester, with the pH back at the
original value of 8.5.
From this experiment, it appears that unproductive hypo-
chlorite decomposition occurs at low pH, and this could in turn
decrease the amount of oxidant available for efficient catalyst
a-Oxidation of ethers and acetals is a potentially interesting
conversion in the fine chemical industry for the production of
complex natural products and for use in carbohydrate chem-
istry, where this reaction is frequently applied for the oxidative
deprotection of hydroxy groups. A mild and selective oxidant
reoxidation. The catalyst is deposited as a precipitate (kdec
>
for this conversion is RuO
4
, which can be conveniently
k
ox), presumably RuO
2
2
3 H O with a water content less than
generated in situ using a Ru precursor and NaIO
4
or hypo-
10% which is virtually inert to oxidation as observed by Mills
chlorite salts.1
and co-workers. The low pH may also have a detrimental effect
7
The methods described in the literature required either a large
on the selectivity toward ester formation, as acid and alcohol are
formed as by-products under these conditions. These data
suggest that the best catalytic performance for ether oxidation
can be obtained in a narrow pH range at alkaline values
(8–9.5).
2
3
amount of ruthenium (25 mol%) or an excess of hypochlorite
9 equiv.), giving moderate selectivity toward ester formation
(
often at incomplete conversion and long reaction times. LiClO
was reported as the most efficient oxidative agent at high
catalytic ratio (0.2 mol% Ru) but long reaction times and
repeated additions of hypochlorite were required to achieve
A similar pH effect was observed for the oxidation of octan-
8
2-ol to octan-2-one via Ru–NaBrO
3
and for the Os-catalysed
4
9
complete conversion. The use of an excess of hypochlorite
aerobic dihydroxylation of olefins. Our experimental setup was
therefore modified in order to keep the pH constant at 9.5, using
a pH-stat device for the whole duration of the catalytic run.†
In a typical experiment, a Ru precursor (see Table 1) was
leads to the formation of copious amounts of sodium chloride
5
waste and hence to a high E factor which decreases the
environmental acceptability of the process.
We reasoned that efficient use of NaOCl (i.e. 2+1 ratio to the
2 2
dissolved in CH Cl and activated with a 4-fold excess of
substrate) should be achieved by optimising the reoxidation of
hypochlorite at room temperature. To this mixture, the substrate
was added quickly, followed by dropwise addition of the
2
the catalyst from its reduced form, presumably RuO , avoiding
3
21
decomposition to inactive insoluble species. In other words, the
rate of the reaction Ru(IV) - Ru(VIII), namely kox, should be
much larger than the rate of decomposition, kdec, throughout the
catalytic run (Scheme 1). We found that simple pH control is the
key to improve the catalytic process and obtain fast selective a-
oxidation of aliphatic symmetrical and unsymmetrical ethers to
esters.
oxidant, at a rate of ca. 0.1 cm min . During this phase, pH
was adjusted by addition of HCl 2.0 M. After complete addition
of NaOCl (2 equiv. overall), pH was observed to drop and was
therefore kept constant by addition of NaOH 2.0 M until the end
of the experiment.
The most relevant results are summarised in Table 1.
Aliphatic symmetrical ethers such as (n-Pr) O and (n-Bu) O
2 2
could be oxidised to the corresponding esters with very good
selectivity in 5 hours (Entries 1–5). (t-Bu)O(Et) (unsymme-
trical) was similarly converted to tert-butyl acetate, the lower
selectivity being ascribed to partial hydrolysis of the product
We generated RuO
4
in solution by dissolving
6
3
[
2 4 2 2
RuCl (dmso) ] 1, 0.05 mmol, in CH Cl , 2 cm , to which
aqueous NaOCl (1.0 M), 0.2 mmol, was added quickly under
stirring at room temperature. After a few minutes the pH of the
stirred biphasic mixture was measured as ca. 9.
In a separate experiment, n-butyl ether (5 mmol) was added
to a solution of 1 (1 mol%) which was preactivated as described
above, under vigorous stirring at 0 °C. To this solution, NaOCl
(
10 mmol) was added dropwise over 2 hours, during which the
temperature was maintained at 0 °C and pH was monitored.
After this time, the conversion stopped and was accompanied by
a sharp decrease of pH from 8.5 to 4.8, as indicated by the
reaction profile, shown in Fig. 1, with formation of a black
precipitate. The reaction mixture was allowed to warm up to
Fig. 1 Oxidation of (n-Bu)
equiv.), CH Cl , 0 °C (2 h)–RT. The oxidant was added in two aliquots
(arrows) at t = 0 and t = 5 h, dropwise at ca. 0.1 cm min rate.
2
O in the presence of 1 (1 mol%), NaOCl (4
2
2
3
21
Scheme 1
2
02
CHEM. COMMUN., 2002, 202–203
This journal is © The Royal Society of Chemistry 2002

Table 1 Catalytic oxidation of aliphatic ethers to estersa
b
%Cc
%Yc
Entry
Substrate
Product
Catalyst /mol%
%S
1
2
3
4
5
6
7
8
9
n-Propyl ether
n-Butyl ether
Propyl propionate
Butyl butyrate
1 (0.5)
1 (0.5)
2 (0.5)
3 (0.25)
4 (0.5)
1 (0.25)d
1 (0.5)
2 (0.25)
82
85
99
88
77
98
99
86
86
80
70
93
77
59
95
73
51
71
44
98
82
93
88
78
97
73
59
83
66
t-Butyl ethyl ether
t-Butyl acetate
d
1 (0.25)
1 (0.5)e
67
f
10
Tetrahydropyran
d-Valerolactone
a
c
3
b
Conditions: substrate (5 mmol), NaOCl (10 mmol), CH
Determined by GLC based on pure samples, isolated yields usually 2–3% lower. EtOAc instead of CH
Cl
2 2
(2 cm ), RT, pH 9.5, 5 h. 1: [RuCl
2
(dmso)
4
], 2: [RuCl
2
2
(dppp) ], 3: TPAP, 4: RuO
2
2
3 H O.
d
, 3 h. e At pH 7.5. f At 20 h.
Cl
2 2
under basic conditions (Entries 7, 8). Oxidation of tetra-
hydropyran (cyclic) to d-valerolactone (Entry 10) was carried
out at ca. neutral pH (7.5) to avoid ring-opening which can
occur at high pH, although this decreased the activity of the
process and required longer reaction time (20 h). Further studies
on the oxidation of cyclic ethers are in progress.
This project was financed by the Dutch Ministry for
Economic Affairs under the Innovation Oriented Projects for
Catalysis scheme (I. O. P. Catalysis project IKA 97005) and the
contribution is kindly acknowledged.
Catalyst screening indicated that numerous precursors can be
used, such as Ru(II) complexes cis-[RuCl
2
(dmso)
4
], 1, and
Notes and references
10
trans-[RuCl
2
(dppp)
2
], 2 (dppp = 1,3-bis(diphenylphosphino-
11
† In a typical experiment, the catalytic run was carried out in a three-necked
)
propane), the Ru(VII) complex [n-Pr
4
N][RuO
O, 4 (as supplied by Acros). For oxidation of
Cl , 3 proved to be a very active precursor at
4
], TPAP, 3,
5
0 cm3 pear-shaped flask containing a magnetic stirrer, equipped with a
and RuO
2
3 H
2
dropping funnel and connected to a Metrohm pH-stat device consisting of
Dosimat, pH meter and Impulsomat. The rate of addition of aqueous NaOCl
butyl ether in CH
2
2
high catalytic ratio (1+400). For this substrate, the best
selectivity was obtained using 2 in 1+200 ratio to the substrate,
possibly due to the stabilising effect of the bidentate ligand on
3
21
(
1.0 M) by dropping funnel was typically 0.1 cm min , whilst HCl (2.0
3
M) and NaOH (2.0 M) were added automatically by Dosimat at 0.5 cm
min rate (usually less than 1 cm each was required) having preset the pH
at 9.5.
21
3
the precursor which may function as a reservoir for RuO
We checked the possibility of replacing CH Cl as the
4
.
2
2
organic phase with more environmentally acceptable solvents.
Ethyl acetate can not only be used successfully to obtain a
biphasic media, but also has a beneficial effect on catalysis. The
selectivity to butyl butyrate increased to 97%, using 0.25 mol%
of 1 in 3 h (Entry 6). A similar effect was observed for the
oxidation of (t-Bu)O(Et), where the selectivity to tert-butyl
acetate increased to 83% (Entry 9). EtOAc may either stabilise
the catalyst in the high oxidation state or decrease the activation
barrier of the polar transition state. The pH control procedure
could be conveniently replaced by a more user-friendly
1
J. L. Courtney, Ruthenium Tetraoxide Oxidations, in Organic Syntheses
by Oxidation with Metal Compounds, eds. W. J. Mijs and C. R. H. I. de
Jonge, Plenum Press, New York, 1986; A. Haines, Methods for the
Oxidation of Organic Compounds, Academic Press, London, 1985; R.
A. Sheldon and J. K. Kochi, Metal-Catalysed Oxidations of Organic
Compounds, Academic Press, New York, 1981.
2 A. B. Smith and R. M. Scarborough, Synth. Commun., 1980, 10, 205.
3 G. Balavoine, C. Eskenazi and F. Meunier, J. Mol. Catal., 1985, 30,
1
25.
4
M. Bressan and A. Morvillo, J. Chem. Soc., Chem. Commun., 1989,
4
2
21; M. Bressan, A. Morvillo and G. Romanello, Inorg. Chem., 1990,
9, 2976.
3 2 3
NaHCO –Na CO buffer (pH 9.5, 1+1 v/v ratio to solvent).
Butyl ether was converted to butyl butyrate with 98% selectivity
using TPAP (0.25 mol%) in EtOAc.
5
6
R. A. Sheldon, CHEMTECH, March 1994, pp. 38–47; R. A. Sheldon, J.
Chem. Tech. Biotechnol., 1997, 68, 381.
E. Alessio, G. Mestroni, G. Nardin, W. M. Attia, M. Calligaris, G. Sava
and S. Zorzet, Inorg. Chem., 1988, 27, 4099.
We are currently investigating the scope of this method,
although we envisage that its applicability may be limited to
substrates not containing carbon–carbon double or triple bonds
7 A. Mills, S. Giddings and I. Patel, J. Chem. Soc., Faraday Trans. 1,
1987, 83, 2317.
8
9
4
which are known to be cleaved by RuO .
S. Giddings and A. Mills, J. Org. Chem., 1988, 53, 1103.
In summary, this study shows that Ru-catalysed bleach a-
oxidation of ethers can be carried out without the need of an
excess of oxidant (as reported so far) whereas the reaction
proceeds at constant pH 9.5; fast complete conversions (as short
as 3 h) and high yields in esters (up to 95%) were obtained by
C. Döbler, G. M. Mehltretter, U. Sundermaier and M. Beller, J. Am.
Chem. Soc., 2000, 122, 10289; C. Döbler, G. M. Mehltretter, U.
Sundermaier and M. Beller, J. Organomet. Chem., 2001, 621, 70.
1
1
0 C. W. Jung, P. E. Garrou, P. R. Hoffman and K. G. Caulton, Inorg.
Chem., 1984, 23, 726.
1 W. P. Griffith, S. V. Ley, G. P. Whitcombe and A. D. White, J. Chem.
Soc., Chem. Commun., 1987, 1625; S. V. Ley, J. Norman, W. P. Griffith
and S. P. Marsden, Synthesis, 1994, 639.
4
efficient reoxidation of Ru to the active catalytic species (RuO )
by optimal use of the terminal oxidant (NaOCl) using
environmentally-friendly organic solvents.
CHEM. COMMUN., 2002, 202–203
203