Catalysis of a hydroxyapatite-bound Ru complex: efficient heterogeneous
oxidation of primary amines to nitriles in the presence of molecular oxygen
Kohsuke Mori, Kazuya Yamaguchi, Tomoo Mizugaki, Kohki Ebitani and Kiyotomi Kaneda*
Department of Chemical Science and Engineering, Graduate School of Engineering Science, Osaka University, 1-3
Machikaneyama, Toyonaka, Osaka 560-8531, Japan. E-mail: kaneda@cheng.es.osaka-u.ac.jp; Tel: +81-6-6850-6260
and Fax: +81-6-6850-6260
Received (in Cambridge, UK) 12th December 2000, Accepted 30th January 2001
First published as an Advance Article on the web 14th February 2001
A hydroxyapatite-bound Ru complex could efficiently cata-
lyze the aerobic oxidation of various primary amines to
nitriles which were further hydrated to amides in the
presence of water.
used as substrate, the oxidation of n-octylamine occurred
exclusively to afford n-octanenitrile in 91% yield for 12 h
without any oxidation products derived from octan-1-ol.‡ Also,
an intramolecular competitive oxidation of 4-(aminomethyl)-
benzyl alcohol afforded chemoselectively 4-cyanobenzyl alco-
hol in a quantitative yield [eqn. (1)] because the amino function
Nitriles are versatile synthetic intermediates which are gen-
erally prepared by nucleophilic displacement of halides with
cyanide ions, ammoxidation, and the Sandmeyer reaction.
These conventional methods often require hazardous reagents
and severe reaction conditions. Direct synthesis of nitriles from
primary amines by the oxidative dehydrogenation is one
powerful candidate for a clean synthesis. Many stoichiometric
reagents in the above dehydrogenation have, however, been
used,1 which often result in the production of a vast amount of
environmental waste.2 Catalytic methods using molecular
oxygen as an oxidant3 are more desirable from the consideration
of ‘green and sustainable chemistry’.2
(1)
coordinates more strongly to a Ru center than the hydroxy one.
2-(1-Cyclohexenyl)ethylamine and geranylamine gave the
allylic and vinylic nitriles in high yields without geometrical
isomerization of double bonds, respectively (entries 13 and 14).
In a secondary amine of dibenzylamine, N-benzylidenebenzyl-
amine could be obtained in 91% yield (entry 16). Other
secondary amines such as N-methylbenzylamine and N-
ethylbenzylamine afforded the corresponding imines accom-
panied with benzaldehyde through the imine hydrolysis.
Oxidation of tertiary amines did not proceed under the present
conditions. The spent RuHAP catalyst was easily separated
from the reaction mixture and the ICP analysis of the filtrate
showed that no leaching of the Ru species was observed during
the above oxidation. This catalyst could be reused with retention
of its high catalytic activity and selectivity for the oxidation
(entry 3).
Interestingly, when water was used as a solvent instead of
toluene under N2 atmosphere, the RuHAP could also catalyze
the hydration reaction of many nitriles, i.e. n-hexanenitrile, n-
octanenitrile, benzonitrile, 4-methoxybenzonitrile, and 3-cya-
nopyridine to afford excellent yields of the corresponding
amides without any formation of carboxylic acids, respectively,
as shown in Table 2. This hydration system using RuHAP has
advantages over other reported methods because of its simple
and clean operation under neutral conditions and its high
reactivity for both aliphatic and aromatic nitriles.6 Finally, the
RuHAP catalyst could be applied to the one-pot synthesis of
nicotinamide, a highly versatile intermediate of nicotinamide
nucleotides, directly from 3-aminomethylpyridine, giving an
excellent yield of a pure amide (Scheme 1).
We have recently succeeded in creating a monomeric Ru3+
species on the surface of hydroxyapatite (RuHAP), which acts
as a highly efficient heterogeneous catalyst for the aerobic
oxidation of various alcohols.4 During the course of these
studies, we have also found and herein wish to report that the
aerobic oxidation of amines to the corresponding nitriles
smoothly occurred in the presence of this RuHAP catalyst.
Compared with other catalysts for this amine oxidation, the
RuHAP system has many advantages as follows: (i) high
catalytic activity for the oxidation of both aromatic and
aliphatic amines under mild reaction conditions, (ii) a reusable
heterogeneous catalyst, (iii) use of molecular oxygen as an
ultimate oxidant, and (iv) applicability to the hydration of
nitriles to amides.
A calcium hydroxyapatite, Ca10(PO4)6(OH)2, was synthe-
sized according to the literature procedure.5 1.0 g of the calcium
hydroxyapatite was stirred at 25 °C for 24 h in 75 mL of a 2.67
3 1022 M aqueous RuCl3 solution. The obtained slurry was
filtered, washed with deionized water and dried overnight at
110 °C, yielding the RuHAP as a dark brown powder (Ru3+
content: 1.69 mmol g21). The surface structure of the present
RuHAP was determined by X-ray absorption fine structure.4 A
typical RuHAP-catalyzed amine oxidation is as follows. Into a
reaction vessel with a reflux condenser were successively
placed the RuHAP (0.2 g, Ru3+: 6.5 mol%), p-xylene (15 mL),
and n-dodecylamine (0.96 g, 5.2 mmol). The reaction mixture
was stirred at 125 °C under atmospheric pressure of O2. After 24
h, the RuHAP was separated by filtration and the organic layer
was distilled to afford pure n-dodecanenitrile (0.88 g, 94%
yield).
We here propose a possible mechanism for this amine
oxidation. Initially, a ligand exchange between an amine and a
surface Cl moiety of the RuHAP4 gives a Ru–NHCH2R species,
followed by elimination to produce a Ru–H species and an
Oxidation of various primary amines is summarized in Table
1. Many benzylic amines were converted into the benzonitriles
in high yields (entries 1–8).† Notably, our RuHAP could
oxidize aliphatic amines to the corresponding nitriles in high
yields (entries 9–12). It is said that aliphatic amines give low
yields of the nitriles in homogeneous Ru-catalyzed systems
such as trans-[RuVI(tmp)(O2)]3a (H2tmp = 5,10,15,20-tetra-
mesitylporphyrin) and RuCl2(PPh3)33c using molecular oxygen.
When an equimolar mixture of n-octylamine and octan-1-ol was
Scheme 1 Reaction conditions: (i) RuHAP (0.1 g), amine (10 mmol),
1,2-diethoxyethane (25 mL), O2 atmosphere, 120 °C, 16 h, (ii) followed by
adding water (5 mL), N2 atmosphere, 150 °C, 48 h.
DOI: 10.1039/b009944i
Chem. Commun., 2001, 461–462
This journal is © The Royal Society of Chemistry 2001
461