Biobased synthesis of acrylonitrile from glutamic acid

Article abstract of DOI:10.1039/c0gc00805b

Glutamic acid was transformed into acrylonitrile in a two step procedure involving an oxidative decarboxylation in water to 3-cyanopropanoic acid followed by a decarbonylation-elimination reaction using a palladium catalyst. The Royal Society of Chemistry.

Full text of DOI:10.1039/c0gc00805b

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COMMUNICATION
Biobased synthesis of acrylonitrile from glutamic acid†
Je´roˆme Le Noˆtre,a Elinor L. Scott,*a Maurice C. R. Franssenb and Johan P. M. Sandersa
Received 12th November 2010, Accepted 25th January 2011
DOI: 10.1039/c0gc00805b
Glutamic acid was transformed into acrylonitrile in a
two step procedure involving an oxidative decarboxyla-
tion in water to 3-cyanopropanoic acid followed by a
decarbonylation-elimination reaction using a palladium
catalyst.
acrylonitrile from a non-fossil source (glycerol) was reported
using microwave irradiation (47% conversion, 80% selectivity).7
However, the use of hydrogen peroxide and ammonia was
necessary to introduce the nitrogen functionality.
Herein we report the synthesis of acrylonitrile, without the
use of additional ammonia, by using glutamic acid in a two step
procedure. The first step involves the oxidative decarboxylation
of glutamic acid to 3-cyanopropanoic acid in water, followed by
a decarbonylation-elimination using a palladium catalyst.
Initially GABA (1), obtained from glutamic acid by enzymatic
decarboxylation,2 was used as a starting material. Here it
was proposed that oxidative decarboxylation to allylamine (2),
followed by dehydrogenation would result in the formation
of acrylonitrile (Scheme 1). The conversion of an amine such
as (2) into a nitrile is a well documented transformation in
literature and several catalytic processes are available.8 However
this is not the case for the formation of terminal alkenes from
carboxylic acids, the first reaction envisaged. Besides the use of a
stoichiometric amount of lead tetraacetate, only a few catalytic
methods are known and the selectivity towards the terminal
alkene is often poor, with alkane or internal alkene formed as
side products. Several methods were tested based on literature
methods such as the use of a heterogeneous catalyst (Pd/C),9
silver salts,10 and homogeneous catalysts.11 Unfortunately we
never succeeded to form allylamine (2) from GABA (1). Even
with protection on the amine function, either no reaction
took place, or cyclisation to 2-pyrrolidone occurred. When
we applied the reaction conditions we previously developed
to selectively form terminal alkenes from carboxylic acids by
decarbonylation-elimination,12 intramolecular decarboxylative
acylation was observed,13 leading to the formation of the ketone
(4) (Scheme 2).
Alternative resources for fossil fuels represent a key research area
due to the depletion of oil feedstocks, increasing oil prices, inse-
curity of supply, and environmental concerns. As a consequence
a lot of effort has been given to the development of alternative
transportation fuels and, to a lesser extent, to the production of
bulk industrial chemicals. However, in the last decade chemurgy
has regained the interest of a number of research institutions and
companies. Amino acids, for instance, appear as an innovative
and economically viable source of nitrogen-containing bulk
chemicals, avoiding the need of energy-intensive processes to
functionalise hydrocarbons with ammonia.1 We indeed have
shown that glutamic acid, available from a wide range of
voluminous waste streams such as dried distiller’s grains and
solubles (DDGS) of the bioethanol production from maize and
wheat, can be converted into g-aminobutyric acid (GABA)2 and
N-methylpyrrolidone (NMP)3 via technically and economically
feasible routes. DDGS has indeed seen its price drift from $140
to $90 per short tonne between 1980 and 2000.4 Around 25% of
proteins can be found in DDGS from maize, in which glutamic
acid is the most abundant amino acid (ca. 20%).5 Considering
an assumed volume of 10% of the total transportation market in
2020 will consist of bio-fuels, an additional 100 millions tonnes
of protein will be produced, corresponding to ca. 20 million
tonnes of glutamic acid available as a cheap bio-based feedstock.
Acrylonitrile is an important bulk chemical used in the
production of a number of chemicals and polymers. The annual
global production reaches ca. 6 million tons with a current price
of ca. €1900 per ton.6 Its main industrial production (SOHIO
process) is based on the conversion of propene and ammonia
at high temperature (400–500 ◦C) in the presence of metal-
oxide catalysts. Recently the first example of the synthesis of
Scheme 1 Initial approach.
aValorisation of Plant Production Chains, Wageningen University and
Research Centre, P.O. Box 17, 6700 AA, Wageningen, The Netherlands.
E-mail: elinor.scott@wur.nl; Fax: +31 317 483011; Tel: +31 317 481172
bLaboratory of Organic Chemistry, Wageningen University and Research
Centre, Dreijenplein 8, 6703 HB, Wageningen, The Netherlands
† Electronic supplementary information (ESI) available: Typical proce-
dures and experimental data. See DOI: 10.1039/c0gc00805b
Scheme 2 Decarbonylation-elimination attempts on GABA (1).
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Thus a new strategy was investigated where 3-cyanopropanoic
acid (5) would be the key intermediate formed from glutamic
acid. First an oxidative decarboxylation of the amino acid
function of glutamic acid would be performed, followed by a
decarbonylation-elimination12 of 3-cyanopropanoic acid which
should give acrylonitrile (3) (Scheme 3).
colour temporarily (from pale yellow to brown-orange) and
gas (CO2) was evolved. It is known that at least 2 equivalents
of oxidant are needed to convert an amino acid function
into a nitrile group.14 However using 2 equivalents of sodium
bromide and sodium hypochlorite, only 57% conversion into 3-
cyanopropanoic acid (5) was obtained after 1 h at 0 ◦C (Table 1,
entry 1). Optimisation of the reaction conditions showed that
an excess of sodium hypochlorite was needed (Table 1, entry 2),
but only a catalytic amount of sodium bromide is required to
reach full conversion (Table 1, entries 3–5), with an optimum
of 0.1 equivalent based on glutamic acid (Table 1, entry 4). The
reaction was repeated on a larger scale (20 mmol of glutamic
acid) and the isolated yield amounted to 70% (Scheme 4).
Scheme 3 New approach for the conversion of glutamic acid to
acrylonitrile (3).
The transformation of amino acids into nitriles has been
studied in the past and different reaction conditions are available
in the literature. For the reaction to proceed a catalytic amount
of bromide cation “Br+” is needed. Different bromide cation
sources can be used either using brominated agents or a
mixture of bromide anion and oxidant. For instance sodium
hypobromite has been used for the oxidative decarboxylation
of amino acids.14 The use of N-bromosuccinimide15 as well as
trichloroisocyanuric acid have also been reported.16
A combination of HBr and hydrogen peroxide,17 a bromide
salt with hydrogen peroxide,18 or with tetrabutylammonium
peroxydisulfate19 as oxidant have been used for bromination
reaction and could be good candidates for the transformation of
amino acids into nitriles. Moreover those reagents can present
a better activity in the presence of vanadium catalysts.20 This
combination with vanadium is directly inspired by nature, where
haloperoxidase enzymes are known to perform this oxidation
reaction.21 Hager et al. have described the use of bromoperox-
idase with hydrogen peroxide and potassium bromide for the
transformation of valine and tyrosine.22
First we decided to try N-bromosuccinimide (NBS, 3 equiva-
lents) and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH, 1.5
equivalents) in phosphate buffer pH 5 at room temperature
for 4 h.15b Although the conversion into 3-cyanopropanoic
acid (5) was almost complete, side products were formed and
purification of the crude mixture remained difficult. How-
ever 3-cyanopropanoic acid (5) was isolated in ca. 40% after
chromatography over silica gel. By trying the combination of
hydrogen bromide with hydrogen peroxide we did not observe
any conversion of glutamic acid into 3-cyanopropanoic acid (5).
We then decided to use in situ-generated sodium hypobromite
on glutamic acid by reacting sodium bromide and sodium
hypochlorite (Table 1). During the dropwise addition of sodium
hypochlorite it was observed that the reaction mixture changed
Scheme 4 Glutamic acid to 3-cyanopropanoic acid (5) using sodium
bromide and sodium hypochlorite.
Recently we reported the optimisation of a catalytic system
able to selectively transform aliphatic carboxylic acids into
terminal alkenes under relatively mild conditions.12 The reaction
follows a decarbonylation-elimination reaction pathway using
acetic anhydride. Acetic acid and carbon monoxide are then
produced and can be potentially recycled and reused. 3-
Cyanopropanoic acid (5) was reacted under these optimised
reaction conditions as depicted in Scheme 5. The reaction
was performed on 0.5 to 1 g scale and after 18 h reaction
carbon monoxide was detected in the reaction atmosphere.
The crude mixture was analysed by proton NMR and showed
a full consumption of the starting material and the presence
of acrylonitrile (3), which was confirmed by GC-MS analysis.
Purification was performed using a micro-distillation set-up and
acrylonitrile (3) was isolated, in pure form, in 17% yield. The
low isolated yield can be explained by the fact that, despite
the presence of a stabilizer (hydroquinone), some insoluble
black material was present in the reaction mixture, which could
come from the degradation of the starting material or the
polymerisation of the product.
Scheme 5 Decarbonylation/elimination reaction of 3-cyanopropanoic
acid (5).
Table 1 Optimisation of the oxidative decarboxylation of glutamic acid
using a combination of sodium bromide and sodium hypochloritea
Entry NaBr (equivalent)
NaOCl (equivalent) Conversion (%)b
In conclusion, we show that acrylonitrile can be prepared
in two steps from glutamic acid. The first step consists of
an oxidative decarboxylation using in situ-generated sodium
hypobromite leading to the formation of 3-cyanopropanoic
acid. We are currently studying the possibility of improving this
transformation by the use of enzymes such as haloperoxidases,21
or by exploring the use of a greener oxidant for the reaction, such
as molecular oxygen.23 The second step allowed the conversion
1
2
3
4
5
2
3
0.5
0.1
0.01
2
3
3
3
3
57
100
100
100
5
a Reaction conditions: glutamic acid (1 mmol, 147 mg), D2O (2 mL),
0 ◦C, 1 h. b Determined by 1H NMR.
808 | Green Chem., 2011, 13, 807–809
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of 3-cyanopropanoic acid into acrylonitrile by a palladium-
catalysed decarbonylation-elimination reaction. Although the
isolated yields need to be improved, we showed that the
conversion was high and we hope that further study of this
transformation, especially towards the stability of acrylonitrile
during the reaction, will lead to better results. Moreover it
appeared to us that 3-cyanopropanoic acid constitutes an
interesting and promising intermediate for the preparation of
other bulk chemicals and further results will be reported in due
course.
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We are grateful to the NWO-ACTS-ASPECT program for
financial support and discussion with industrial collaborators
DSM and BASF.
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