Alkene and alkyne oxidative cleavage catalyzed by RuO4 in environmentally acceptable solvents

Article abstract of DOI:10.1081/SCC-120022466

The application of CCl₄, C₆Hl₂, EtOAc, and Me₂CO as solvents for biphasic systems has been compared for oxidative cleavage of alkenes and alkynes by RuO₄ to carboxylic acids, using the RuCl₃·nH₂O-IO(OH)₅ reagent for which an improved procedure is described. Cyclohexane is an effective and economic replacement for the environmentally unfriendly CCl ₄; acetone and ethyl acetate are less effective.

Full text of DOI:10.1081/SCC-120022466

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Alkene and Alkyne Oxidative Cleavage Catalyzed by
RuO in Environmentally Acceptable Solvents
4
a
a
William P. Griffith & Eugene Kwong
a
Imperial College of Science, Department of Chemistry, Technology and Medicine, London,
UK
Version of record first published: 21 Aug 2006
To cite this article: William P. Griffith & Eugene Kwong (2003): Alkene and Alkyne Oxidative Cleavage Catalyzed by RuO4
in Environmentally Acceptable Solvents, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 33:17, 2945-2951
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 17, pp. 2945–2951, 2003
Alkene and Alkyne Oxidative Cleavage
Catalyzed by RuO in Environmentally
Acceptable Solvents
4
William P. Griffith* and Eugene Kwong
Imperial College of Science, Department of Chemistry,
Technology and Medicine, London, UK
ABSTRACT
The application of CCl
biphasic systems has been compared for oxidative cleavage of
alkenes and alkynes by RuO to carboxylic acids, using the
RuCl O–IO(OH) reagent for which an improved procedure
ꢀ nH
is described. Cyclohexane is an effective and economic replacement
4 6 2
, C H12, EtOAc, and Me CO as solvents for
4
3
2
5
for the environmentally unfriendly CCl
are less effective.
4
; acetone and ethyl acetate
Key Words: Alkenes; Alkynes; Carbon tetrachloride; Cyclohexane;
Ruthenium tetroxide.
*
Correspondence: William P. Griffith, Imperial College of Science, Technology
and Medicine, Department of Chemistry, London, SW7 2AY UK; E-mail:
w.griffith@ic.ac.uk.
2
945
DOI: 10.1081/SCC-120022466
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2
946
Griffith and Kwong
Ruthenium tetroxide (RuO ) is used in organic synthesis principally
4
for oxidative alkene and alkyne cleavage and for the oxidation of sec-
[
1,2]
ondary alcohol functions in sugars.
Since it is toxic and volatile it is
usually made in situ from RuCl ꢀ nH O or RuO ꢀ nH O with a cooxidant,
3
2
2
2
[
normally sodium periodate, NaIO . A biphasic system is often used:
3]
4
RuCl ꢀ nH O or RuO ꢀ nH O is reacted with NaIO in water and the
3
2
2
2
4
RuO is extracted into CCl , currently the most commonly used solvent
4
4
for such oxidations. The efficiency of such systems is improved by addi-
[4]
tion of a little CH CN.
3
The use of carbon tetrachloride (CTC) as a solvent is becoming
5]
[
increasingly untenable owing to CFC regulations. There is therefore a
real need for an acceptable organic solvent for such reactions, one in
which RuO is soluble but not attacked by it. There are few such solvents
4
because RuO is so reactive, but attempts have been reported using
4
[
6,7]
[8,9]
materials other than CCl , principally acetone
or ethyl acetate.
Dichloromethane, chloroform, and acetone are inferior to CCl for
4
4
[
RuO -catalysed oxidations of hydrobenzoin and sugars; 1,2-dichloro-
10]
4
ethane has recently been used for oxidation of alkenes to aldehydes using
[
11]
RuCl ꢀ nH O/NaIO .
3
2
4
We have shown that RuCl ꢀ nH O with periodic acid, IO(OH) as
3
2
5
cooxidant, generating RuO in situ, is effective for the oxidative cleavage
4
[
12]
of alkenes and alkynes to carboxylic acids.
Here we describe an
improved procedure for using this reagent, and show that it may effec-
tively be used with the more eco-friendly and much cheaper cyclohexane
replacing CCl as the organic solvent.
4
RESULTS AND DISCUSSION
[
12]
In our method
CCl –CH CN–H O, extracting the products with dichloromethane.
we used RuCl ꢀ nH O and IO(OH)5 in
3
2
4
3
2
We find that better results are achieved by using diethyl ether as the
13]
[
extractant (see Table 1); Nunez and Martı
˜
´
for oxidizing 1-hexene to pentanoic acid.
n
used a similar method
Use of Various Solvents
CCl4
This is currently the solvent of choice for most RuO -catalyzed
4
oxidations. In the table oxidations of alkenes, alkynes, and hydrobenzoin
using AnalaR CCl4 are reported. For such oxidations, addition of

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Cleavage of Alkenes and Alkynes
2947
Table 1. Oxidation of alkenes and alkynes to carboxylic acids with RuO4
generated from RuCl
3
ꢀnH
2
O-IO(OH)
5
in various solvents.
Solvent
2
12 EtOAc Me CO Time/h
Substrate
Product
CCl
4
C
6
H
Styrene
Benzoic acid
Suberic acid
Pimelic acid
Adipic acid
Glutaric acid
84 [14]* 72 [15] 81 [15] 10 [2]
83 [15] 97 [18] 92 [15] 78 [13]
72 [16] 77 [15] 57 [12] 59 [12]
84 [18] 74 [19] 83 [21] 31 [7]
1
cis-Cyclooctene
Cycloheptene
Cyclohexene
Cyclopentene
1.5
2
1.5
2
66 [20] 67 [18] –
58 [7] 64 [7]
–
–
1
-Dodecene
Phenylacetylene
Diphenylacetylene Benzoic acid
Hydrobenzoin Benzoic acid
Undecanoic acid 58 [7]
2
Benzoic acid
90 [17] 86 [15] 43 [9] 53 [11]
76 [17] 80 [18] 72 [15] 66 [13]
86 [15] 88 [15] 47 [8] 80 [13]
2
2
0.5
*
TO ¼ turnover (moles of product/moles catalyst).
[4]
CH CN is desirable: in its absence the yield of benzoic acid from
3
styrene, for example, dropped from 84% in 1 h to 14% in 3 h. AnalaR
[
15]
or Spectrosol
RuO . The sensitivity of even AnalaR CCl to RuO is shown by our
CCl must be used since impurities rapidly degrade
4
4
4
4
electronic spectra: RuO extracted into it showed the two typical peaks of
4
[14]
the tetroxide
at 310 and 385 nm for only 30 min, by which time the
solution had perceptibly darkened, due to traces of oxidizable material in
the solvent.
Cyclohexane
There has been no reported systematic study on the use of cyclohex-
ane as a solvent for oxidations with RuO . In the table we show its utility
4
as a replacement for CCl in a 1:1:2 C H :CH CN:H O mixture. Being
2
4
6
12
3
less dense than water, C H forms the upper layer of the biphasic system,
6
12
but this presents no practical problems. Oxidations using HPLC grade
99.9%þ) C H gave essentially the same yields and turnovers as normal
(
grade C H , so specially purified cyclohexane is not needed. As with
6
12
6
12
CCl , CH CN enhances the yield: for oxidation of styrene to benzoic
4
3
acid the yield of the latter dropped from 72% in 1 h to 12% in 2 h in
the absence of CH CN.
3
Electronic spectra of RuO extracted into C H showed the tetrox-
12
4
6
ide peaks centered on 312 and 382 nm with attendant fine structure;

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Griffith and Kwong
[12]
Raman spectra also show the presence of RuO by the appearance of
4
À1
the 881 cm ꢀ (Ru¼O) peak. After 30 min there is only a slight darken-
s
ing of the solution; there was essentially no difference if 99.9 þ % HPLC-
grade solvent was used.
Ethyl Acetate
Ethyl acetate has been used with RuO for oxidations of 1,6-dienes to
4
[
8]
trans-2,6-bis(hydroxymethyl)-tetrahydropyrandiols
[
and of cyclic a-
9]
amino acids to a-aminodicarboxylic acids. Like cyclohexane EtOAc is
less dense than water and so lies above the aqueous layer. For oxidative
cleavage we find that yields are lower than those obtained from CCl and
4
C H , although use of high-purity HPLC (99.8%þ) reagent gave better
6
12
results for oxidations of cycloheptene and of phenylacetylene. Whereas
RuO4 extracted into EtOAc darkens within the first 15 min for the
normal purity reagent, the electronic spectral peaks appearing at 309
and 385 nm, with 99.95% HPLC grade darkening sets in only after
45 min.
Acetone
Acetone–water mixtures have been used for the RuO -catalyzed
4
oxidation of substituted monoene steroids to a-hydroxyketones and/or
diols, while Piatak et al. used a similar system for cleavage of aromatic
[6]
[7]
steroids. In the table we list oxidations using AnalaR acetone; results
are significantly poorer than those for CCl , C H or EtOAc, and both
4
6
12
1
melting point and H NMR data show that the oxidation products are
less pure than those obtained from CCl or C H . Electronic spectra too
show that RuO , while present in freshly-prepared acetone–water
4
6
12
4
solutions, deteriorates significantly within half an hour.
CONCLUSIONS
Cyclohexane is an excellent replacement for CCl in oxidations with
4
RuO for the cleavage of cyclic alkenes, terminal alkenes, alkynes, and
4
hydrobenzoin to carboxylic acids. From electronic and Raman spectra it
is clear that RuO is relatively stable in cyclohexane and gives similar or
4
better yields of cleavage products than does CCl as a solvent. It is likely
4
that it could be used to replace CCl in other RuO -catalyzed reactions.
4
4

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Cleavage of Alkenes and Alkynes
EXPERIMENTAL
2949
Materials were obtained from Aldrich except RuCl ꢀ nH O (n ꢁ 2.5)
3
2
which was from Johnson, Matthey. Products were identified by melting
1
points, IR, and H NMR spectra.
Oxidations Using CCl as Solvent
4
[
12]
In our earlier procedure
we used dichloromethane to extract the
acids formed by alkene or alkyne cleavage effected with this reagent, but
find that diethyl ether is more effective. Cleavage of cyclohexene to adipic
acid is typical. To cyclohexene (0.165 g, 2 mmol) was added RuCl ꢀ nH O
3
2
3
(
0.024 g, 0.12 mmol) and IO(OH) (2.4 g, 10.5 mmol) in water (10 cm ),
5
3
CCl (5 cm ) and CH CN (5 cm ). The mixture was stirred for 1.5 h at
3
4
3
3
room temperature and Et O (20 cm ) added with further stirring for
1
2
3
0 min. The reaction mixture was extracted with Et O (25 cm ꢂ 3) and
2
the extract dried over MgSO (2 g) for 15 min. The product was isolated
4
by concentration with a rotary evaporator.
Oxidations with Other Solvents
In all cases our improved extraction procedure, using diethyl ether
rather than dichloromethane, was used.
Cyclohexane
Cleavage of styrene to benzoic acid is typical. To styrene (0.208 g,
mmol) was added RuCl ꢀ nH O (0.024 g, 0.12 mmol) and IO(OH)
2
(
(
3
2
5
3
2.4 g, 10.5 mmol) in water (10 cm ), C H
3
(5 cm ) and CH CN
6 12 3
3
5 cm ). The mixture was stirred for 1 h at room temperature; extraction
and isolation was effected as with CCl4.
Ethyl Acetate
[
A procedure modified from that of Piccialli was used. Thus, to
8]
cycloheptene (0.192 g, 2 mmol) was added RuCl ꢀ nH O (0.024 g,
3
2
3
.115 mmol) and IO(OH) (2.4 g, 10.5 mmol) in water (10 cm ), EtOAc
0
(
5
3
3
5 cm ) and CH CN (5 cm ). The mixture was stirred for 2 h at room
3

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2
950
Griffith and Kwong
temperature. Extraction and isolation followed the procedure outlined
for C H above.
6
12
Acetone
[
A procedure modified from that of Piccialli was used. Thus, to
6]
diphenylacetylene (0.36 g, 2 mmol) was added RuCl ꢀ nH O (0.024 g,
3
2
3
0
.12 mmol) and IO(OH) (2.4 g, 10.5 mmol) in water (10 cm ), Me CO
5
2
3
3
(
5 cm ) and CH CN (5 cm ). The mixture was stirred for 2 h at room
3
temperature; extraction and isolation followed the procedure outlined
for C H above.
6
12
Instrumentation
Electronic spectra were measured on a Perkin Elmer Lambda 2
UV/VIS spectrophotometer, Raman spectra on a Dilor LabRam
1
Infinity spectrometer with He–Ne excitation at 632.8 nm, and H NMR
2
spectra on a Bruker DRX-400 instrument in H O using 10 mm tubes.
2
ACKNOWLEDGMENTS
We thank Johnson, Matthey for loans of hydrated ruthenium
trichloride.
REFERENCES
1
2
. Griffith, W.P. Chem. Soc. Revs. 1992, 21, 179–185.
. Martın, V.S.; Palaz, J.M.; Rodrıguez, C.M. Encyclopaedia of
´
´
Reagents for Organic Syntheses, Paquette, L. Ed.; John Wiley:
Chichester, 1995, 6, 4415–4422.
. Nakata, H. Tetrahedron 1963, 19, 1959–1963.
3
4
´
. Carlsen, P.H.J.; Katsuki, T.; Martın, V.S.; Sharpless, K.B. J. Org.
Chem. 1981, 46, 3936–3938.
5. J. de Fouw, Environmental Health Criteria 208: Carbon Tetrachloride,
World Health Organisation, Geneva, 1999, 28–36.
6. Piccialli, V.; Smaldone, D.M.A.; Sica, D. Tetrahedron 1993, 49,
4211–4228.

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Cleavage of Alkenes and Alkynes
2951
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. Piatak, D.M.; Herbst, G.; Wicha, J.; Caspi, E. J. Org. Chem. 1969,
4, 116–120.
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. Yoshifuji, S.; Tanaka, K.; Kawai, T.; Nitta, Y. Chem. Pharm. Bull.
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Carbohydr. Res. 1968, 6, 431–435.
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1. Yang, D.; Zhang, C. J. Org. Chem. 2001, 66, 4814–4818.
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2000, 30, 3091–3095.
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1
3. Nunez, M.T.; Martın, V.S. J. Org. Chem. 1990, 55, 1928–1932.
˜
´
4. Griffith, W.P.; Suriaatmaja, M. Can. J. Chem. 2001, 79, 598–606;
Connick, R.E.; Hurley, C.R. J. Amer. Chem. Soc. 1952, 74,
5012–5015.
15. Giddings, S.; Mills, A. J. Org. Chem. 1988, 53, 1103–1107.
Received in the UK November 19, 2002

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