Solvent-free microwave-assisted peroxidative oxidation of secondary alcohols to the corresponding ketones catalyzed by copper(ii) 2,4-alkoxy-1,3,5-triazapentadienato complexes

Article abstract of DOI:10.1039/b922738e

A facile, efficient and selective solvent-free synthesis of ketones from secondary alcohols with tert-butylhydroperoxide (TBHP) as the oxidant under microwave irradiation is achieved, where the copper(ii) 2,4-alkoxy-1,3,5- triazapentadienato complexes are efficient catalysts providing high yields (up to 100%), TONs (up to 890) and TOFs (up to 1780 h^-1).

Full text of DOI:10.1039/b922738e

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Solvent-free microwave-assisted peroxidative oxidation of secondary
alcohols to the corresponding ketones catalyzed by copper(II)
2,4-alkoxy-1,3,5-triazapentadienato complexesw
a
a
a
ab
´
Pawe$ J. Figiel, Maximilian N. Kopylovich, Jamal Lasri, M. Fatima C. Guedes da Silva,
Joao J. R. Frau
´
sto da Silvaa and Armando J. L. Pombeiro*a
Received (in Cambridge, UK) 30th October 2009, Accepted 9th February 2010
First published as an Advance Article on the web 25th February 2010
DOI: 10.1039/b922738e
A facile, efficient and selective solvent-free synthesis of ketones
from secondary alcohols with tert-butylhydroperoxide (TBHP)
as the oxidant under microwave irradiation is achieved, where
the copper(II) 2,4-alkoxy-1,3,5-triazapentadienato complexes
are efficient catalysts providing high yields (up to 100%), TONs
(up to 890) and TOFs (up to 1780 hꢀ1).
MW irradiation. Favourable features, a priori, of such
complexes include their easy synthesis, cheapness, environ-
mental tolerance, good stability under oxidizing conditions
and solubility in the alcohol substrate which allows
elimination of the use of another solvent and of a phase
transfer agent.
Copper catalysts are known6 for the oxidation of alcohols,
but usually their catalytic systems show the above limitations
and often are less or not active for the oxidation of simple
aliphatic alcohols.5a,6a,b,12 To our knowledge, not one example
of a simple Cu-based system with low catalyst loadings for
solvent- and halogen-free oxidation of aliphatic alcohols has
been reported, before the current study.
Ketones are among the most important chemicals, as final
products or for further synthesis, e.g. as polymer precursors or
substrates in the pharmaceutical industry.1 Although they can
be synthesized by direct oxidation of alkanes2,3 or alkenes,4
these reactions are usually not selective.2 The liquid-phase
oxidation of secondary alcohols to ketones appears to be the
simplest and the most used synthetic method.3,5 However,
these reactions are commonly limited to benzylic compounds6
and need relatively high catalysts loadings,5 long reaction
time6 and/or additives (bases, phase-transfer agents, etc.),5,6
as well as oxidants (e.g. manganese salts, chromates)1,7 and
solvents6b,c,7,8 that often are expensive and toxic. Moreover,
the catalysts used are frequently expensive (based on noble
metals),9 not easy to prepare and not highly active for the
oxidation of aliphatic alcohols.6 Hence, the search for other
synthetic systems for ketones which would overcome at least
some of the above limitations is a matter of current interest.
Of particular significance would be the establishment of a
solvent-free process10 eventually assisted by microwave (MW)
irradiation (an alternative to the traditional heating, with the
usual advantages11 of reducing the reaction time and promoting
the yield, selectivity and purity of products), and using
environmentally acceptable and efficient catalyst and oxidant,
under mild conditions. These are the general aims of the
current study which focuses on the unprecedented application
of a type of copper complex beariꢀng triazapentadienate
ligands, i.e. HNQC(R)NC(R0)QNH , as highly efficient
and selective catalysts for such a reaction, under focused
In this work we used the CuII alkoxy-1,3,5-triazapenta-
dienato complexes [Cu{NHQC(OR)NC(OR)QNH}2] (R =
Me 1, Et 2), which can be easily prepared in one step, by a
modification of a known13 method, using simple and cheap
starting materials i.e. Cu(NO3)2, sodium dicyanamide and
methanol or ethanol. The reaction involves the template
nucleophilic addition of the alcohol to each of the cyano
groups of NRCꢀNꢀCRNꢀ, and the derived triazapenta-
dienato acts as a chelating ligand as in other square-planar,
air-, thermo- and moisture-stable CuII complexes.14
Complex 1 is already known13 and thus will not be discussed
here in detail. The IR spectrum of 2 shows no n(CRN) band,
while n(NH) and n(CQN) are observed at 3335, 3306 and
1607 cmꢀ1, correspondingly. The crystal structure of 2z shows
the Cu atom (Fig. 1) is in an inversion centre and displays
a square-planar coordination environment with two uni-
negatively charged 1,3,5-triazapentadienato chelators. In the
six-membered planar metallacycles, the N–Cu–N bite angles
and the Cu–N bond distances are close to those in relevant
CuII bis-1,3,5-triazapentadienates.13,14 The N1–C1 and
N2–C2 distances of 1.294(3) and 1.300(3) A, respectively, are
typical of Csp2QN bonds,15 while the N3–C1 [1.336(3) A] and
N3–C2 [1.344(4) A] distances are characteristic of planar
Csp2Nsp2 groups,15 therefore revealing bond delocalization in
the metallacycle ring. The O2 containing alkoxy arms are
bending out of the metallacycle plane, presenting
C2–O2–C4–C6 dihedral angles of ca. 82.861. A striking feature
is the intermolecular contacts between each terminal C6
methyl group of one molecule and the delocalized electronic
clouds of the metallacycles of two vicinal molecules, showing a
C–Hꢁ ꢁ ꢁp interaction. A related (but intramolecular aromatic–
aromatic) interaction was reported for other CuI–containing
metallacycles.16 The distance of 2.848 A between the H6c
a
´
´
Centro Quımica Estrutural, Complexo I, Instituto Superior Tecnico,
TU Lisbon, Av. Rovisco Pais, 1049-001, Lisbon, Portugal.
E-mail: pombeiro@ist.utl.pt; Fax: +351 218464455
b
´
Universidade Lusofona de Humanidades e Tecnologias,
ULHT Lisbon, Campo Grande 376, 1749-024 Lisbon, Portugal
w Electronic supplementary information (ESI) available: 1: General
materials and instrumentation. 2: Synthesis of catalysts. 3: Details of
the X-ray crystal structure analysis and refinement. 4: Experimental
details of catalytic activity studies. 5: Supporting catalytic and
structural figures, and selected bonding parameters. CCDC 752593.
For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/b922738e
ꢂc
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Fig. 1 ORTEP plot shown at 30% probability of the molecular
structure of 2; the hydrogens are omitted for clarity. Symmetry
transformations used to generate the equivalent atoms: (i) ꢀx, ꢀy, ꢀz.
Fig. 2 Acetophenone formation vs. time (catalyst 1): MW assisted
hydrogen and the metallacycle centroid, and the
C6–H6cꢁ ꢁ ꢁcentroid angle of 137.761, indicate a relatively
strong non-covalent interaction (Fig. S2, ESIw). The joint
effects of bending of the alkoxy arms and the intermolecular
p interaction led to a 3D network with two distinct layers of 2
that are displaced relatively by an angle of ca. 83.351 (Fig. S3,
ESIw). The structure is further stabilized by weak inter-
molecular H-bonding interactions involving the O1 oxygens
of one molecule as acceptors and the H3b and H4b hydrogens
of two neighbouring molecules as donors (Fig. S2, ESIw).
Both complexes 1 and 2 were tested as catalysts for the
oxidation of secondary alcohols to ketones by TBHP (2 eq.) in
the absence of solvent (Scheme 1). The oxidation of 1-phenyl-
ethanol to acetophenone was used as a model reaction to
optimize conditions. Selected results are summarized in
Table 1, revealing that the MW assisted reaction proceeds
rapidly even under the low irradiation power of 10 W;
increasing the power did not show a significant yield enhance-
ment. In the presence of a catalytic amount of 1 (0.01 mmol;
0.2 mol% vs. substrate), a fair yield of acetophenone
(58%, run 1) was already achieved in 15 min, whereas the
quantitative yield was obtained in 30 min (run 2, Fig. 2) under
MW irradiation, with high TON and TOF values of 500 and
1000 hꢀ1, respectively. The system is highly effective even in
the presence of lower catalyst amounts (0.005 mmol; 0.1 mol%
vs. substrate; TON = 890; TOF = 1780 hꢀ1; yield = 89%;
run 3) (cf. common 4–5% catalyst load for other systems6).
Under the same conditions but using conventional heating
(oil-bath) instead of MW only 4% of product (run 4, Fig. 2)
was formed after 30 min. Extending the reaction time to
300 min still resulted in a lower yield (81%, run 5) than that
(100%, run 2) for the MW assisted process after only 30 min.
The MW promoted reaction in the presence of 2 gave similar
results to 1 (run 6), while the simple salt Cu(NO3)2 or the
(1) and conventional (2). For conditions, see Table 1.
Table 1 Oxidation of 1-phenylethanola
Run Catalyst
MW T/1C t/min TONb (TOFc) Yieldd (%)
1
1
1
1
1
1
2
Yes 80
Yes 80
Yes 80
15
30
30
30
300
30
30
30
30
30
30
30
290 (1160)
500 (1000)
890 (1780)
20 (40)
405 (81)
485 (970)
185 (370)
200 (400)
—
100 (200)
330 (660)
50 (100)
85 (21)
58
100
89
4
81
97
37
40
9
20
66
10
17
2
3e
4
No
No
80
80
5
6
7
8
Yes 80
Cu(NO3)2 Yes 80
Cu(acac)2 Yes 80
None
1
1
1
1
9
Yes 80
Yes 80
Yes 80
Yes 50
Yes 50
10f
11g
12
13
240
a
Reaction conditions: 5 mmol of substrate, 0.01 mmol of catalyst
b
(0.2 mol% vs. substrate), 10 mmol of TBHP (2 eq.). Turnover
number = number of moles of acetophenone per mol of catalyst.
c
d
Turnover frequency = TON per hour (values in parentheses). GC
e
yield, acetophenone was detected as the only product. 0.005 mmol
f
(0.1 mol% vs. substrate) of 1 used. Hydrogen peroxide (10 mmol, 2 eq.)
g
used instead of TBHP. Reaction with 5 mmol (1 eq.) of TBHP.
related isoelectronic [Cu(acac)2] complex were much less active
(runs 7–8), pointing out the importance of the triazapenta-
dienato ligands. In the absence of any catalyst, only 9% of
acetophenone was found after 30 min under MW (run 9).
Hydrogen peroxide is a much less effective oxidant than TBHP
(run 10 vs. 2). Two eq. of TBHP vs. substrate are required
[a stoichiometric amount leads to a significant yield decrease
(run 11)]. The effect of the reaction temperature is stronger for
the MW assisted process (runs 12–13, Fig. S1, ESIw), where
80 1C is the optimum value.
Based on the optimization results, we have chosen 1
(0.2 mol% vs. substrate) as a model catalyst under MW
irradiation at 80 1C in the presence of 2 eq. TBHP for the
futher study of oxidation of aliphatic alcohols (Table 2). As
expected, these alcohols are less reactive than the benzylic
ones. Thus, the oxidation of 2-hexanol yields 25% of
2-hexanone in 30 min (Table 2, run 1), although for a
sufficiently longer time (240 min) a good yield was obtained
(90%, Table 2, run 2), as well as e.g. for 3-hexanol, cyclo-
hexanol and 2-octanol (yields of 82, 97 and 85%, runs 3, 4 and 5,
respectively). For comparative purposes, we also tested
1-hexanol as a substrate, which was selectively oxidized with
Scheme 1 MW-assisted oxidation of secondary alcohols to ketones.
ꢂc
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Table 2 Oxidation of selected alcohols catalyzed by 1a
3 (a) G. Tojo and M. Fernandez, Oxidation of Alcohols to Aldehydes
and Ketones: A Guide to Current Common Practice, Springer,
New York, 2006; (b) W. C. E. Arends and R. A. Sheldon, Modern
Oxidation Methods, ed. J.-E. Backvall, Wiley-VCH, Weinheim,
2004, p. 83.
4 (a) M. G. Speziali, V. V. Costa, P. A. Robles-Dutenhefner and
E. V. Gusevskaya, Organometallics, 2009, 28, 3186;
(b) B. R. Travis, R. S. Narayan and B. Borhan, J. Am. Chem.
Soc., 2002, 124, 3824; (c) H. Okumoto, K. Ohtsuko and
S. Banjoya, Synlett, 2007, 3201.
5 (a) I. E. Marko, P. R. Giles, M. Tsukazaki, S. M. Brown and
C. J. Urch, Science, 1996, 274, 2044; (b) D. Bogda" and
M. Łukasiewicz, Synlett, 2000, 143.
6 (a) G. Ferguson and A. N. Ajjou, Tetrahedron Lett., 2003, 44,
9139; (b) G. Rothenberg, L. Feldberg, H. Wiener and Y. Sasson,
J. Chem. Soc., Perkin Trans. 2, 1998, 2429; (c) R. Chakrabarty,
P. Sarmah, B. Saha, S. Chakravorty and B. K. Das, Inorg. Chem.,
2009, 48, 6371.
Run Substrate
t/min Product
TONb (TOFc) Yieldd [%]
1
2
3
2-Hexanol
2-Hexanol
3-Hexanol
30 2-Hexanone
240 2-Hexanone
240 3-Hexanone
125 (250)
450 (112)
410 (102)
25
90
82
97
85
45
4
Cyclohexanol 240 Cyclohexanone 485 (121)
2-Octanol
1-Hexanol
5
240 2-Octanone
425 (106)
6e
240 Hexanoic acidf 225 (56)
a
Reaction conditions: 5 mmol of substrate, 0.01 mmol of 1 (0.2 mol%
b
vs. substrate), 10 mmol of TBHP (2 eq.), MW, at 80 1C. See footnote
b of Table 1. See footnote c of Table 1. Based on GC analyses,
c
d
e
f
100% selectivity in all cases. 20 mmol of TBHP (4 eq). No hexanal
detected by GC.
4 eq. TBHP to hexanoic acid in 45% yield (Table 2, run 6).
The obtained yields of aliphatic ketones with our system are
generally higher than with other known MW-assisted oxidations
of secondary alcohols.8 Although mechanistic details are still not
clear, preliminary experiments with radical traps (which are
shown to strongly hamper the catalytic activity, Fig. S4, ESIw)
suggest the involvement of a radical pathway.6b,17
7 (a) J. Singh, M. Shana, M. Chibber, J. Kaur and G. L. Kad, Synth.
Commun., 2000, 30, 3941; (b) D. Pandey and D. S. Kotari, Oxid.
Commun., 2009, 32, 371.
8 (a) L. Palombi, F. Bonadies and A. Scetti, Tetrahedron, 1997, 53,
15867; (b) C. Gonzalez-Arellano, J. M. Campelo, D. J. Macquarrie
and J. M. Marinas, ChemSusChem, 2008, 1, 746.
9 (a) A. Corma and H. Garcia, Chem. Soc. Rev., 2008, 37, 2096;
(b) L. Tonucci, M. Nicastro, N. d’Alessandro, M. Bressan,
P. D’Ambrosio and A. Morvillo, Green Chem., 2009, 11, 816.
10 M. Alizadeh, F. Farzaneh and M. Ghandi, J. Mol. Catal. A:
Chem., 2003, 194, 283.
11 (a) Microwaves in Organic Synthesis, ed. A. Loupy, Wiley/VCH,
Weinheim, 2002; (b) ed. J. P. Tierney and P. Lidstrom, Microwave
Assisted Organic Synthesis, Blackwell Publishing/CRC Press,
Oxford, 2005.; (c) D. Dallinger and C. O. Kappe, Chem. Rev.,
2007, 107, 2563; (d) V. Polshettiwar and R. S. Varma, Acc. Chem.
Res., 2008, 41, 629; (e) G. Keglevich, T. Novak, L. Vidac and
I. Greiner, Green Chem., 2006, 8, 1073.
In summary, we found that Cu alkoxy–triazapentadienato
complexes are remarkably active catalysts in the MW-assisted
oxidation of secondary alcohols to ketones, by TBHP.
Reactions are fast, selective, require a small amount of catalyst
and proceed in the absence of any additional solvent or
additives, features of significance towards the development
of a ‘‘green’’ catalytic process for such a type of reaction. The
investigation of the synthesis and activity of other CuII
triazapentadienates as well as kinetic and mechanistic studies
are in progress.
12 (a) T. Punniyamurthy and L. Rout, Coord. Chem. Rev., 2008, 252,
134; (b) S. C. Mohapatra, S. Tehlan, M. S. Hundal and P. Mathur,
Inorg. Chim. Acta, 2008, 361, 1897; (c) R. S. Varma and R. Dahiya,
Tetrahedron Lett., 1998, 39, 1307.
This work has been supported by the Fundacao para a
Ciencia e a Tecnologia (FCT), Portugal, and its PPCDT
program (FEDER funded). J. L. and M. N. K thank FCT
for their research contracts and P. J. F. for a post-doc grant.
13 (a) R. Boca, M. Hvastijova, J. Kozısek and M. Valko, Inorg.
Chem., 1996, 35, 4794; (b) M.-L. Tong, Y.-M. Wu, Y.-X. Tong,
X.-M. Chen, H.-C. Chang and S. Kitagawa, Eur. J. Inorg. Chem.,
2003, 2385; (c) L.-L. Zheng, J.-D. Leng, W.-T. Liu, W.-X. Zhang,
J.-X. Lu and M.-L. Tong, Eur. J. Inorg. Chem., 2008, 4616.
14 (a) N. Heße, R. Frohlich, I. Humelnicu and E.-U. Wurthwein,
Eur. J. Inorg. Chem., 2005, 2189; (b) I. Hager, R. Frohlich and
E.-U. Wurthwein, Eur. J. Inorg. Chem., 2009, 2415;
(c) M. N. Kopylovich, K. V. Luzyanin, M. Haukka, A. J. L.
Pombeiro and V. Yu. Kukushkin, Dalton Trans., 2008, 5220;
(d) H. V. R. Dias and S. Singh, Inorg. Chem., 2004, 43, 5786;
(e) H. V. R. Dias, J. A. Flores and J. Wu, J. Am. Chem. Soc., 2009,
131, 11249; (f) J.-P. Zhang, Y.-Y. Lin, X.-C. Huang and
X.-M. Chen, J. Am. Chem. Soc., 2005, 127, 5495;
(g) M. S. Zhou, Y. P. Song, T. Gong, H. Tong, J. P. Guo,
L. Weng and D. Liu, Inorg. Chem., 2008, 47, 6692.
Notes and references
z X-Ray crystal analysis of 2: C12H20CuN6O4, M = 375.88, mono-
clinic, P21/c (no. 14), a = 12.6923(13), b = 8.2392(10), c = 8.6199(10) A,
b = 90.190(2)1, U = 901.42(18) A3, T = 296 K, Z = 2, Dc
=
1.385 Mg mꢀ3, m = 1.238 mmꢀ1, F(000) = 390, 5757 reflections
measured, 2613 unique (Rint = 0.0584), R1 (I 4 2s(I)) = 0.0434,
wR2 = 0.1105.
1 (a) Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH,
Weinheim, 6th edn, 2002; (b) R. A. Smiley and H. L. Jackson,
Chemistry and the Chemical Industry, CRC Press, Boca Raton, FL,
2002; (c) Process Chemistry in the Pharmaceutical Industry,
ed. K. Gadamasetti and T. Braish, CRC Press, Boca Raton, FL,
vol. 2, 2008.
15 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer,
A. G. Orpenand and R. Taylor, J. Chem. Soc., Perkin Trans. 2,
1987, S1.
16 S. Chowdhury, M. G. B. Drew and D. Datta, Inorg. Chem.
Commun., 2003, 6, 1014.
2 (a) L. I. Matienko, L. A. Mosolova and G. E. Zaikov, Russ. Chem.
Rev., 2009, 78, 211; (b) N. Komiya, S. Noji and S.-I. Murahashi,
Chem. Commun, 2001, 65; (c) N. Komiya, T. Naota and
S. I. Murahashi, Tetrahedron Lett., 1996, 37, 1633.
17 (a) A. Lattanzi, P. Iannece and A. Scettri, Tetrahedron Lett., 1999,
40, 3899; (b) R. R. Fernandes, M. V. Kirillova, J. A. L. da Silva,
J. J. R. Frausto da Silva and A. J. L. Pombeiro, Appl. Catal., A,
2009, 353, 107.
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This journal is The Royal Society of Chemistry 2010
2768 | Chem. Commun., 2010, 46, 2766–2768