Ruthenium-catalyzed aerobic oxidative decarboxylation of amino acids: A green, zero-waste route to biobased nitriles

Article abstract of DOI:10.1039/c5cc00181a

Oxidative decarboxylation of amino acids into nitriles was performed using molecular oxygen as terminal oxidant and a heterogeneous ruthenium hydroxide-based catalyst. A range of amino acids was oxidized in very good yield, using water as the solvent. This journal is

Full text of DOI:10.1039/c5cc00181a

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Ruthenium-catalyzed aerobic oxidative
decarboxylation of amino acids: a green,
zero-waste route to biobased nitriles†
Cite this: Chem. Commun., 2015,
1, 6528
5
Received 8th January 2015,
Accepted 6th March 2015
Laurens Claes, Jasper Verduyckt, Ivo Stassen, Bert Lagrain and Dirk E. De Vos*
DOI: 10.1039/c5cc00181a
www.rsc.org/chemcomm
Oxidative decarboxylation of amino acids into nitriles was performed first report on oxidative amino acid decarboxylation using mole-
using molecular oxygen as terminal oxidant and a heterogeneous cular oxygen as the sole oxidant and a ruthenium-based catalyst,
ruthenium hydroxide-based catalyst. A range of amino acids was without involvement of halides or halonium species. Various
oxidized in very good yield, using water as the solvent.
nitriles were produced in water under mild conditions and, more
importantly, in a fully salt-free process.
Nitrogen-based functionalities, in particular amines and
First, simple ruthenium compounds were evaluated on their
amides, are present in a broad range of commodity and fine activity in the oxidative decarboxylation of leucine, which serves
chemicals. They are often prepared by hydrogenation or hydra- as a model amino acid (Table 1). Reactions were performed in
tion of nitriles, which are themselves the result of the metal- water, at 100 1C and initially under high oxygen pressure to avoid
catalyzed incorporation of nitrogen into an organic backbone. shortage of dissolved oxygen. With a homogeneous catalyst like
Exemplary industrial processes are the ammoxidation of pro- RuCl , high conversions were obtained within 24 h. The reaction
3
pylene into acrylonitrile or the hydrocyanation of butadiene proceeds faster in neutral or basic media after adjusting the
1
into adiponitrile. Nevertheless, the harsh process conditions pH of the aqueous solution of RuCl
3
. Irrespective of the pH,
or the need for toxic reagents (e.g. HCN) are strong incentives to nitrile selectivity was affected by the consecutive hydration to
1
4,15
explore milder production routes.
the corresponding amide (entries 1–4).
Earlier studies on
Proteins isolated from non-edible biomass, for instance the the related aerobic oxidation of primary benzylamines and
waste from agro-industry, biofuel production and slaughterhouses,
provide an excellent renewable resource for producing N-containing
Table
1
Catalyst screening for aerobic oxidative decarboxylation
2
chemicals. Recently, we have shown that amino acids, obtained by of leucine
hydrolytic protein depolymerization, can be recycled directly and
with high selectivity into functionalized nitriles via bromonium-
3
mediated oxidative decarboxylation. In the conversion of glutamic
4
5
acid and glutamine into biobased acrylonitrile, adiponitrile and
a
b
Catalyst
—
X
[%]
S [%]
6
succinonitrile, this oxidative decarboxylation has been identified
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
o1
66
499
499
94
o1
499
499
499
499
499
88
—
83
78
75
88
—
78
76
80
69
40
78
82
84
85
14
as a key step. However, product workup may be complex with
RuCl
RuCl
RuCl
3
3
3
, pH 4
, pH 7
, pH 10
7
halonium-type oxidants, e.g. N-bromosuccinimide. Catalytic
3,8,9
halide oxidation allows to reduce the waste load significantly,
c
Ru(acac)
g-Al
Ru(OH)
3
but the reaction still suffers from limited yields based on hydrogen
peroxide, and from an undesired oxidative ring halogenation of
2
O
3
x
2 3
/g-Al O
3
n+
d
aromatic amino acids.
Ru /hydroxyapatite
Ru(OH)
Ru(OH)
Ru(OH)
Ru(OH)
Ru(OH)
x
x
x
x
x
x
/hydroxyapatite
/ZrO
/hydrotalcite
/TiO
/CeO
/Co
Inspired by the transition metal-catalyzed oxidation of primary
0
1
2
3
4
5
6
2
10–13
amines into nitriles using green oxidants,
we here present the
2
2
O
68
55
46
499
Centre for Surface Chemistry and Catalysis, Department of Microbial and
Molecular Systems, KU Leuven – University of Leuven, Kasteelpark Arenberg 23,
post box 2461, 3001 Heverlee, Belgium. E-mail: Dirk.DeVos@biw.kuleuven.be
Ru(OH)
3
4
0
e
Ru /Al
2
O
3
0
e
Ru /C
†
Electronic supplementary information (ESI) available: Experimental details, data
on catalyst characterization (PXRD, SEM, EDX, N physisorption) and additional
results on oxidative decarboxylation. See DOI: 10.1039/c5cc00181a
a
d
b
c
2
Leucine conversion. Isovaleronitrile selectivity. Acac: acetylacetonate.
Prepared by ion-exchange of Ca with Ru .
2+
3+ 12a e
0
5 wt% Ru on support.
6
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aliphatic amines in water demonstrated that ruthenium cata-
1
4b
lyzes both amine oxidation and nitrile hydration;
the latter
1
2e
reaction already occurs to a minor extent at 100 1C. Literature
shows that one may increase the nitrile yield by working in
1
1a,12a
12b
nonpolar solvents like toluene
or trifluorotoluene, but
such media are unsuitable to dissolve zwitterionic amino acids.
While keeping water as the solvent, a significant improvement
of the nitrile selectivity, even at high conversion, was achieved
by using Ru(acac) instead of RuCl (entry 5).
3 3
Given the remarkable activity of ruthenium in amino acid
oxidative decarboxylation, supported ruthenium catalysts were
evaluated next, since they offer advantages in terms of product Fig. 1 Ru-catalyzed aerobic oxidation of n-pentylamine (E ) and leucine
(
’) as pure compounds (closed symbols) and in a 1 : 1-mixture (open
symbols). Conditions: substrate (0.2 mmol), Ru(OH) /g-Al (5 mol% Ru),
O (2 mL), O (30 bar), 100 1C; the Ru-loading was 2.5 mol% in the com-
separation and metal recyclability. Typical catalysts were prepared
according to the method of Mizuno and coworkers: ruthenium was
immobilized onto a support by precipitation-deposition as hydrous
x
2 3
O
H
2
2
petitive experiment.
12
ruthenium oxide in highly alkaline medium. Candidate supports
were commercially available oxides such as g-Al , ZrO , TiO
anatase), CeO and Co , from which many successful catalysts
have been developed for aerobic amine oxidation.
2
O
3
2
2
(
2
3
O
4
x 2 3
The substrate scope of the Ru(OH) /g-Al O catalyst was
12b–i
Also hydroxy- successfully extended towards other amino acids bearing an
1
2a
apatite and hydrotalcite were selected because slightly basic aliphatic moiety, such as alanine (2a), valine (3a), isoleucine
conditions seem to be beneficial for amino acid oxidation. (4a) and norleucine (5a) (Table 2). These compounds behave
Characterization by powder X-ray diffraction (PXRD) allowed similarly as leucine (1a): near-complete conversion is reached
to confirm that the structures of the supports were retained within 24 h, with a nitrile selectivity around 80%. Also glutamate
during alkaline deposition; via elemental analysis, the catalyst’s (6a), which is the most abundant amino acid constituent from
2
actual ruthenium content was determined (Fig. S1–S10† and protein-rich waste streams derived from plant biomass, was
Tables S1 and S2†). It is well known that such a deposition converted for 80% with high selectivity to the bifunctional nitrile
n+
0
procedure results in ionic Ru , rather than metallic Ru on the 6b. Interestingly, aspartate (7a) was much less reactive. On the one
1
2h,16
support.
High conversions of leucine were observed using ionic surface Ru species. On the other hand, the electron-withdrawing
ruthenium supported on g-Al , ZrO , hydroxyapatite and carboxylate group of the side chain is closer to the reactive
hydrotalcite (Table 1, entries 7–11). The lower activity of the a-carbon atom in aspartate than in glutamate; it is conceivable
hand, this could be due to a chelating effect of the aspartate on
n+
2
O
3
2
n+
2 2 3 4
TiO -, CeO - and Co O -supported catalysts could be due to that the amino acid oxidation by Ru is more sensitive to such
lower external surface areas, resulting in poor metal dispersion, electronic effects than the oxidative decarboxylation by strongly
3
but also the acid–base properties of the supports could play a role oxidizing halonium species. A decreased reactivity was also
(
entries 12–14, Table S3†). In addition to the catalysts based on observed for homoserine (8a), whereas serine and threonine
0
ionic ruthenium, also metallic Ru catalysts supported on Al O
and carbon were evaluated (entries 15 and 16). Although full catalysts facilitate aerobic alcohol oxidation as well, resulting
conversion of leucine was obtained with Ru /C, nitrile selectivity in complex product mixtures.
showed little if any reaction. In addition, supported ruthenium
2
3
1
7
0
was very low; the main reaction was an oxidation at the beta-
x 2 3
The heterogeneity of the Ru(OH) /g-Al O catalyst was demon-
carbon atom, leading to further skeleton breakdown and isobu- strated in the oxidative decarboxylation of 6a. After 2 h, when the
tyric acid formation. Clearly, the presence of ionic ruthenium is conversion was at 11%, the catalyst was separated and the filtrate
essential for selective oxidation. The most performant catalysts, did not show any residual activity (Fig. S14†). The catalyst was
viz. Ru(OH) /g-Al O and Ru(OH) /hydroxyapatite induce a weakly successfully recycled several times in the reaction of 1a; while
x
2
3
x
basic pH in the aqueous solution (Table S3†).
substantial activity remained in the re-use cycles, the reaction rates
Upon variation of the reaction conditions it became clear were lower (Table S4†). As for the oxidation of simple amines, it
that oxidative decarboxylation also proceeds smoothly at lower might be necessary to optimize the catalyst recycling procedures.
oxygen pressures, e.g. 5 bar (Fig. S11†). The reaction is first order
The oxidative decarboxylation of leucine proceeds much more
in ruthenium (1–5 mol%, Fig. S12†) and by using a catalyst slowly than the oxidation of n-pentylamine; the latter reaction
loading of 5 mol%, full leucine conversion is reached within an remains preferred in competitive experiments (Fig. 1). However, in
acceptable time frame (Fig. 1). The mild reaction temperature of previous work from our group on alcohol racemization using
n+
1
00 1C is close to the optimum: at slightly higher temperatures supported ionic Ru , it was found that the presence of carboxyl-
(
e.g. 110 1C) a similar nitrile yield can be obtained within even ates inhibited the dehydrogenation of alcohols on supported
n+ 18
shorter reaction times, whereas leucine conversion is significantly Ru . In this respect, the high activity of ruthenium cata-
slower at 80 1C (Fig. S13†). When the reaction was performed lysts for amino acid dehydrogenation is remarkable, especially
at 150 1C for 24 h, isovaleramide was obtained as the major in case of glutamate 6a, which even contains an additional
product (76% yield).
carboxylate group.
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Table 2 Scope of the Ru-catalyzed aerobic oxidative decarboxylation of
amino acids
a
b
Amino acid
Nitrile
X [%]
S [%]
9
9
75
83
81
79
Scheme 1 Proposed mechanism for the Ru-catalyzed oxidative decarboxyl-
ation of a-amino acids in the presence of molecular oxygen.
À
4
99
99
by replacement of the nitrile product by an incoming OH or
fresh reactant.
In conclusion, alumina-supported hydrous ruthenium oxide
is an efficient catalyst for oxidative decarboxylation of amino
acids into nitriles and amides using molecular oxygen. Several
aliphatic and functionalized amino acids are transformed
successfully in water under mild conditions without producing
halide waste.
4
LC, JV and IS are grateful to IWT Flanders and FWO Flanders
for PhD fellowships. BL thanks KU Leuven (IOF-ZKC6712).
DEDV acknowledges BELSPO (IAP-PAI P7/05) and the Flemish
government (Methusalem grant CASAS) for structural funding.
We thank Karel Duerinckx for assistance with NMR measurements.
8
8
9
0
85
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19
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2h,16
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