Selective oxidation of a single primary alcohol function in oligopyridine frameworks

Article abstract of DOI:10.1021/ol0491843

(Equation Presented) A variety of mono-oxidized pyridine, bipyridine, terpyridine, and pyridine/pyridazine are readily prepared under mild conditions using Pyrolusite MnO₂. This phase has been characterized by means of X-ray powder diffraction

Full text of DOI:10.1021/ol0491843

ORGANIC
LETTERS
2
004
Vol. 6, No. 17
865-2868
Selective Oxidation of a Single Primary
Alcohol Function in Oligopyridine
Frameworks
2
,†
†
†
‡
Raymond Ziessel,* Patrick Nguyen, Laurent Douce, Mich e` le Cesario, and
§
Claude Estournes
Laboratoire de Chimie, d’Electronique et de Photonique Mol e´ culaires, Associ e´ au
CNRS ESA-7008, Ecole de Chimie, Polym e` res, Mat e´ riaux de Strasbourg (ECPM), 25,
rue Becquerel, 67087 Strasbourg Cedex 02, France, Institut de Chimie des Substances
Naturelles, CNRS, F-91128 Gif-sur-YVette, France, and Groupement des Mat e´ riaux
Inorganiques, IPCMS, 23 rue du Loess, 67034 Strasbourg Cedex 02, France
ziessel@chimie.u-strasbg.fr
Received May 4, 2004
ABSTRACT
A variety of mono-oxidized pyridine, bipyridine, terpyridine, and pyridine/pyridazine are readily prepared under mild conditions using Pyrolusite
MnO . This phase has been characterized by means of X-ray powder diffraction and scanning electron microscopy. The oxidative activity is
in keeping with the nature, morphology, and surface area of the MnO
2
2
reagent.
In the past decades and nowadays there has been a steady
and progressive interest in convenient methods for the
selective oxidation of primary alcohols to the corresponding
aldehydes, and an impressive number of protocols are now
available. The most popular methods for the oxidation of
hydes bearing donor groups has driven research into new
and improved procedures leading to functionalized oligopy-
ridines. Among these methods the use of tert-butoxybis-
(dimethylamino)methane (Bredereck’s reagent) is promising.6
In a general sense, aldehydes are very interesting targets
for the synthesis of so-called Schiff base compounds, which
attract much interest in the field of coordination chemistry.
The presence of a lone pair on the nitrogen atom of the imine
group enables the coordination of numerous metal cations,
especially when the imine function is located at the ortho
position of the heterocycle such as in pyridine. Recently,
various molecules found interesting applications as ligands
in homogeneous catalytic reactions such as hydrosilation,
1
alcohols use activated dimethyl sulfoxide (Swern protocol),
pyridinium chlorochromate (Collins reagent and analogues),
2
N-chlorosuccinimide oxidation of alkoxymagnesium bro-
3
4
mides, and tetraalkylammonium per-ruthenate reagent. In
one case, the use of barium manganate allows the selective
(
85%) mono-oxidation of 2,5-diphenyl-3,4-di(hydroxymeth-
5
yl)thiophene. The recent interest in the synthesis of alde-
†
7
Ecole de Chimie, Polym e` res, Mat e´ riaux de Strasbourg (ECPM).
Institut de Chimie des Substances Naturelles.
Groupement des Mat e´ riaux Inorganiques, IPCMS.
Mukaiyama aldolization and cyclopropanation, homologa-
‡
8
9
§
tion of aromatic aldehydes, and ethylene polymerization.
(
1) (a) Mancuso, A. J.; Swern, D. Synthesis 1981, 165. (b) Tidwell, T.
T. Synthesis 1990, 857.
2) (a) Collins, J. C.; Hess, W. W.; Frank, F. J. Tetrahedron Lett. 1968,
363. (b) Corey, E. J.; Schmidt, G. Tetrahedron Lett. 1979, 399 and
references therein.
3) Narasaka, K.; Morikawa, A.; Saigi, K.; Mukaiyama, T. Bull. Chem.
Soc. Jpn. 1977, 50, 2773.
4) Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D. Chem.
Commun. 1987, 1625.
In all of these applications the synthesis of the starting
(
(5) Firouzabadi, H.; Mostfavipoor, Z. Bull. Chem. Soc. Jpn. 1983, 56,
3
914.
(6) Dupau, P.; Renouard, T.; Le Bozec, H. Tetrahedron Lett. 1996, 37,
(
7503.
(7) Dias, E. L.; Brookhart, M.; White, P. S. Chem. Commun. 2001, 423.
(8) Dias, E. L.; Brookhart, M.; White, P. S. J. Am. Chem. Soc. 2001,
123, 2442.
(
1
0.1021/ol0491843 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/29/2004

aldehydes remains challenging and difficult. Recently, we
have developed a direct and convenient synthesis of imines
from bipyridine frameworks where the aldehyde function is
Scheme 1
1
0
masked in the form of a gem-dibromomethyl derivative.
Interestingly, the selective oxidation of a single primary
alcohol in 2,6-di(hydroxymethyl)pyridine is possible but
remains difficult and feasible only under harsh conditions.
2
Typical literature procedures utilize SeO (0.5 equiv) in
refluxing pyridine.11 This is a major problem due to the
toxicity, cost, product purity, and low isolated yields. In our
hands, this was a significant issue that could not be overcome
by manipulating the reaction and purification conditions. We
desired conditions that would be practical, inexpensive,
environmentally friendly, and amenable to large-scale syn-
thesis and that allow for substrate generality.
The use of other metal reagents or catalysts has been
developed to address this issue. Manganese dioxide has
proved a valuable oxidizing agent for certain functional
1
2
groups. This reagent oxidizes many compounds smoothly.
However, we noticed that 2,6-di(hydroxymethyl)pyridine was
doubly oxidized to the bisaldehydes in acceptable yield, but
at that time no characterized side products were mentioned
and the exact nature of the manganese dioxide was not
1
3
given. Despite these advances, there still remained a need
for a general protocol that would efficiently broaden the
scope of this important oxidation reaction. In this Letter, we
disclose the results of using manganese dioxide for the
selective mono-oxidation of oligopyridine carrying dihy-
droxymethyl functions.
2
Next, we chose to better characterize the MnO by
determining the specific surface, the nature of the phase (by
X-ray powder diffraction), and the morphology. First, we
were pleased to discover that the MnO
surface area of 3.8 m /g and a much better resolved dif-
2
(P) sample has a low
2
Initial results revealed that a sample of MnO
2
(P) from
2
fraction pattern when compared to MnO
The first sample, MnO (P), exhibits some sharp diffraction
lines that can be attributed unambiguously to the Pyrolusite
2
(M) (46.7 m /g).
Rh oˆ ne Poulenc (Prolabo no. 25 259.296) in a stoichiometric
ratio with the starting material was weakly active and only
2
provided the monoxidized derivative 1 in CHCl
3
at 60 °C.
1
4
phase (SI). The second sample, MnO
and broad diffraction peaks emerging from the background
that are attributed to a ꢀ-MnO Akhtenskite phase (SI).
2
(M), exhibits weak
However, a sample of MnO (M) from Merck (no. 805958)
2
was very active and provided solely the di-oxidized com-
pounds. After some experimentation, we were pleased to find
that we could isolate compound 1 in 70% using a large excess
2
Furthermore, the morphology of the two manganese oxide
samples has been characterized using scanning electron
of MnO
ridine derivatives as depicted in Scheme 1. The best solvent
is CHCl , which gives a correct balance between the
2
(P) and extend the protocol to a family of oligopy-
microscopy. For MnO
larger than tens of microns are observed (Figure 1, top),
whereas the second sample [MnO (M)] is composed of
2
(P), platelet-like crystallites with sizes
3
2
solubility of the products, the kinetics of the reaction, and
the selectivity. In all cases the formation of the bisaldehydes
is negligible (<5%) and the unreacted compounds could be
easily recycled. The presence of oxygen is not mandatory
for the oxidation, and lower temperatures provide lower
yields for the oxidation. We also noticed that the use of other
solvents such as dichloromethane, pyridine, or acetone and
ultrasonic irradiation do not significantly improved the yields.
aggregates of a mixture of irregular shaped grains and needles
of a few nanometers (Figure 1, bottom).
There is a close relation between the morphology of the
crystallites, the specific surface area, and the activity of the
material. The larger crystals have a lower surface area and
better resolved diffraction patterns but also a weaker oxida-
tion capability, leading specifically to the mono-oxidized
2
compounds. The more dispersed MnO (M) material is less
(
9) (a) Small, B. L.; Brookhart, M.; Bennett; A. M. A. J. Am. Chem.
Soc. 1998, 120, 4049. (b) Small, B. L.; Brookhart, M. J. Am. Chem. Soc.
998, 120, 7143. (c) Britovsek, G. J. P.; Gibson, V. C.; Kimberley, B. S.;
crystallized, more dispersed, and consequently more active
toward primary alcohol oxidation, and in this case double
oxidation is always evidenced with 2,6-di(hydroxymethyl)-
pyridine. Preparation of the active MnO Pyrolusite phase
2
could be achieved according to literature procedures.15
1
Maddox, P. J.; McTavish, S. J.; Solan, G. A.; White, A. J. P.; Williams, D.
J.; Bruce, M.; Mastroianni, S.; Redshaw, C.; Str o¨ mberg, S. J. Am. Chem.
Soc. 1999, 121, 8728.
(10) Weibel, N.; Charbonni e` re, L.; Ziessel, F. R. J. Org Chem. 2002,
6
7, 7876.
(
(
11) Mathes, W.; Sauermilch, W. Chem. Ber. 1956, 89, 1515.
12) (a) Attenburrow, J.; Cameron, A. F. B.; Chapman, J. H.; Evan, R.
M.; Hems, B. A.; Jansen, A. B. A.; Walker, T. J. Chem. Soc. 1952, 1094.
(14) Hill, L. I.; Verbaere, A.; Guyomard, D. J. Electrochem. Soc. 2003,
150, 135 and references therein.
(15) Hill, L. I.; Verbaere, A.; Guyomard, D. J. Power Sources 2003,
119-121, 226.
(
b) Lou, J.-D.; Xu, Z.-N. Tetrahedron Lett. 2002, 43, 6149.
13) Papadopoulos, E. P.; Jarrar, A.; Issidorides, C. H. J. Org Chem.
966, 31, 615.
(
1
2866
Org. Lett., Vol. 6, No. 17, 2004

3 3
of trace amounts of acid (CH COOH for R ) CH and
p-TsOH for R ) R and R ). To avoid the trans esterification
2
3
byproduct with the free hydroxymethyl function and to
achieve a better yield in the imine formation, p-TsOH was
preferred instead of acetic acid.
Encouraged by the successful preparation of the imino
derivatives, we moved to the more ambitious goal of
expanding the methodology to the use of aliphatic diamino
compounds in order to produce ditopic ligands for metal
complexation. Ligands 12 and 13 were successfully prepared
in good yields, by condensation of 2 equiv of 2-formyl-6-
(hydroxymethyl)pyridine with ethylenediamine in the pres-
ence of trace amounts of acetic acid (Scheme 3).
Scheme 3
Figure 1. SEM micrographs recorded for the two MnO
top) MnO (P) Pyrolusite phase, and (bottom) ꢀ-MnO Akhtenskite
phase.
2
samples:
(
2
2
One of the objectives of the selective mono-oxidation of
diols was to transform the resulting aldehyde function to a
Schiff base and to evaluate them in coordination chemistry
and material science. The remaining hydroxy group will act
as an organizing vector in the solid state in order to stabilize
tridimensional structures via hydrogen bonds. By analogy
To test the coordination abilities of such ligands toward
transition metal and to generate simple metal-induced self-
organized structures, ligand 12 was allowed to react under
16
to our previous work, and also stimulated by our involve-
ment in a program devoted to the engineering of mesomor-
phic nanostructures, we condensed 2-formyl-6-(hydroxy-
methyl)pyridine with aniline derivatives bearing in the para
position an additional phenyl-ester dipole and carrying at
their peripheries three paraffin chains. In one case, one of
these alkyl chains is substituted by an acrylate function, a
potential module for controlled polymerization reactions
stoichiometric and anaerobic conditions with [Cu(CH
BF ) salts.
Immediately after mixing the ligand with the metal salt, a
3 4
CN) ]-
(
4
deep-red color, characteristic of Cu-imino derivatives, de-
veloped in the solution. This coloration is indicative of a
Cu(I) cation surrounded by four nitrogen donor atoms.18
FT-IR studies in solution and in the solid state of the resulting
17
(
Scheme 2). After some experimentation, we were pleased
-
1
complex showed a 21 cm shift of the imino stretching
to find that these condensations can effectively be performed
under mild conditions and with fair yields in the presence
vibration, confirming that no free imino function at νCdN
-
1
1
650 cm was present. Furthermore, the proton NMR
spectrum of the Cu-complex in CD CN solution revealed
3
the presence of an AB system (exo-H: 4.57 ppm, J ) 15.3
Hz. endo-H: 3.77 ppm, J ) 15.3 Hz), whereas in the free
ligand a singlet was found at 4.89 ppm. This prochirality of
the methylene protons is consistent with the imino-pyridine
fragments becoming more rigid as a result of coordination
Scheme 2
1
9
to the metal center. ES-MS revealed the presence of an
+
intense molecular peak at 809.2 [M - BF
4
] and 361.1 [M
2
+
-
2BF
Interestingly, because of intermolecular hydrogen-bonding
interactions, no νOH peak for a free OH group (around 3600
4
]
typical of a dinuclear species.
(16) (a) El-ghayoury, A.; Douce, L.; Skoulios, A.; Ziessel, R. Angew.
Chem., Int. Ed. 1998, 37, 2205. (b) Douce, L.; El-ghayoury, A.; Skoulios,
A.; Ziessel, R. Chem. Commun. 1999, 2033.
(17) Percec, V.; Ahn, C.-H.; Bera, T. K.; Ungar, G.; Yeardley, D. J. P.
Chem. Eur. J. 1999, 5, 1070.
(
18) Juris, A.; Ziessel, R. Inorg. Chim. Acta 1994, 225, 251.
(19) Buda, M.; Moutet, J.-C.; Saint-Aman, E.; De Cian, A.; Fisher, J.;
Ziessel, R. Inorg. Chem. 1998, 37, 4146 and references therein.
Org. Lett., Vol. 6, No. 17, 2004
2867

-
1
cm ) could be detected for the solid samples (anhydrous
two metal centers to give a double strand helicate. Each
ligand chelates the two imino/pyridine fragments with two
Cu(I) centers, providing a distorted tetrahedral arrangement
with bite angles of 77.5(2)° to 82.4(2)°. The Cu(I)-Npyr
bonds lie in the 2.053(5)-2.081(5) Å range, whereas the
Cu(I)-Nim lengths are in the 2.009(5)-2.034(5) Å range.
As might be expected, a certain degree of flexibility of the
ligands is required to allow the helicate formation. It should
be noticed that if the pyridine rings are roughly perpendicular
two by two about the metal center, the whole dinuclear
complex reveals a pronounced dissymmetry. Two pyridine
rings N11A and N21B are parallel [deviation of only 2.5-
KBr) of the copper(I) complex. The νOH stretching vibrations
are broader and appeared around 3445 cm . In the free
ligand 12, this νOH peak is shifted to 3220 cm owing to
the presence of hydrogen bond accepting groups. To further
characterize the molecular structure of the binuclear complex
and the plausible hydrogen bonding network we have
undertaken an X-ray molecular structure determination
-
1 20
-
1
21
(
Figure 2).
(1)°], and the two other rings N21A and N11B are perpen-
dicular [81.2(2)°].
Consequently, the molecular structure is extended to 12.4
Å along the axis a and reveals a pronounced π-π stacking
(of about 3.8 Å) between the pyridine rings N11A and N11B.
This π stacking interaction contributes to the stability of the
complex. Furthermore, the crystal structure is stabilized by
hydrogen bond interactions involving the four alcohol
functions and forms a tight 3D H-bonded network. Two
different hydrogen bonds interlink the dimeric structure.
Representative distances are: O18A [x,y,z]‚‚‚O28B [x,1+y,z]
d ) 2.874(9) Å and O28B [x,y,z]‚‚‚O18A [x,-1+y,z] d )
2
.874(9) Å, interlinking two complexes translated along
the c axis: O18B [x,y,z]‚‚‚O28A [x,1-y,-0.5+z] d )
2
2
.944(11) Å and O28A [x,y,z]‚‚‚O18B [x,1-y, 0.5+z] d )
.944(11) Å. Recently, similar polymeric arrays self-as-
sembled by hydrogen-bond aggregation have been evi-
2
2
denced.
In conclusion, we have developed an expedient and
synthetically useful, operationally simple, and general method
for the preparation of monoformyl/monohydroxymethyl
pyridine based molecules. This synthesis uses a Pyrolusite
2
phase of MnO that has been properly characterized by X-ray
diffraction. The oxidative activity is related to this phase but
also to the morphology and surface area of the reagent.
Formation of a multitopic ligand was found to occur
smoothly between the formyl and the target amines, in the
presence of specific amounts of acids and without significant
sides reactions such as trans esterification. In addition, some
of these ligands form dinuclear complexes with Cu(I) salts,
which makes these compounds an attractive and available
template for coordination and material chemistry.
]2+ helicate
2 2
Figure 2. (Top) ORTEP drawing of the [Cu (12)
showing the 30% probability thermal ellipsoids. The hydrogen
atoms are drawn as small spheres of arbitrary radi. (Bottom) The
interlinked hydrogen-bonded network.
Supporting Information Available: Experimental pro-
cedures and characterization for all compounds, X-ray
powder diffraction of the MnO samples, and CIF file for
2
the Cu complex. This material is available free of charge
via the Internet at http://pubs.acs.org.
The crystal structure confirms the formation of a binuclear
metallo-helicate with the two copper(I) centers being sepa-
rated by a distance of 3.902 Å. The ligands wrap around the
(
20) Yoza, K.; Amanokura, N.; Ono, Y.; Akao, T.; Shinmori, H.;
Takeuchi, M.; Shinkai, S.; Reinhoudt, D. N. Chem. Eur. J. 1999, 5, 2722.
21) Douce, L.; Ziessel, R.; Lai, H.-H.; Lin, H.-C. Liq. Cryst. 1999, 26,
797.
OL0491843
(
(22) Lavalette, A.; Tuna, F.; Clarkson, G.; Alcock, N. W.; Hannon, M.
J. Chem. Commun. 2003, 2666.
1
2868
Org. Lett., Vol. 6, No. 17, 2004