Synthesis of biobased succinonitrile from glutamic acid and glutamine

Article abstract of DOI:10.1002/cssc.201100030

Succinonitrile is the precursor of 1,4-diaminobutane, which is used for the industrial production of polyamides. This paper describes the synthesis of biobased succinonitrile from glutamic acid and glutamine, amino acids that are abundantly present in many plant proteins. Synthesis of the intermediate 3-cyanopropanoic amide was achieved from glutamic acid 5-methyl ester in an 86 mol % yield and from glutamine in a 56 mol % yield. 3-Cyanopropanoic acid can be converted into succinonitrile, with a selectivity close to 100 % and a 62 % conversion, by making use of a palladium(II)-catalyzed equilibrium reaction with acetonitrile. Thus, a new route to produce biobased 1,4-diaminobutane has been discovered. Copyright

Full text of DOI:10.1002/cssc.201100030

DOI: 10.1002/cssc.201100030
Synthesis of Biobased Succinonitrile from Glutamic Acid
and Glutamine
Tijs M. Lammens,*[a] Jꢀrꢁme Le Nꢁtre,[a] Maurice C. R. Franssen,[b] Elinor L. Scott,*[a] and Johan
P. M. Sanders[a]
Succinonitrile is the precursor of 1,4-diaminobutane, which is
used for the industrial production of polyamides. This paper
describes the synthesis of biobased succinonitrile from gluta-
mic acid and glutamine, amino acids that are abundantly pres-
ent in many plant proteins. Synthesis of the intermediate 3-cy-
anopropanoic amide was achieved from glutamic acid 5-
methyl ester in an 86 mol% yield and from glutamine in a
56 mol% yield. 3-Cyanopropanoic acid can be converted into
succinonitrile, with a selectivity close to 100% and a 62% con-
version, by making use of a palladium(II)-catalyzed equilibrium
reaction with acetonitrile. Thus, a new route to produce bio-
based 1,4-diaminobutane has been discovered.
Introduction
The chemical industry is in transition from a petrochemical
based toward a more biobased industry. Large-scale produc-
tion of biobased chemicals is becoming a reality. For example,
the viability of the production of epichlorohydrin from glycerol
is demonstrated by Solvay in a plant, which has been in opera-
tion since 2007.[1] The current worldwide research effort direct-
ed toward the development of biobased chemicals is enor-
mous.[2] Most of this research focuses on the use of carbohy-
drates, but the proteins left in by-product streams, from, for
example, bioethanol and biodiesel production, could also be
valuable building blocks for chemicals. Especially the non-es-
sential amino acids in these proteins, which have no significant
value for food or feed, can be interesting starting materials for
a variety of nitrogen-containing products.[3] The most abun-
dant (non-essential) amino acid in many plant proteins is gluta-
mic acid.[4] In previous studies, we demonstrated a possible
production of g-aminobutyric acid,[5] N-methylpyrrolidone and
N-vinylpyrrolidone,[6] and acrylonitrile[7] from glutamic acid.
This paper describes the synthesis of succinonitrile from glu-
tamic acid. Succinonitrile, produced commercially from acrylo-
nitrile and hydrogen cyanide,[8] is the precursor of 1,4-diamino-
butane (DAB, putrescine) in the industrial production of the
polyamides Stanylꢂ and EcoPaXXꢃ.[9] The volume of DAB pro-
duced in Europe each year is estimated to be approximately
10000 tons.[3] Recently, the fermentative and enzymatic pro-
duction of DAB was described.[10] However, DAB is very soluble
in water and, therefore, difficult to isolate from a fermentation
broth. The production of biobased succinonitrile can be an ad-
vantageous route toward the production of biobased nylon, as
it can be readily isolated using extraction with organic sol-
vents. Biobased succinonitrile can be produced from sugar-de-
rived succinic acid, which has received an increased attention
as a versatile, biobased building block.[11] Recently, the reaction
of ammonia with succinic acid, in the presence of Si3(PO4)4 as a
catalyst, was reported to give succinonitrile at a yield of 70%
and at 4208C.[12] Although this is a promising route to prepare
biobased succinonitrile, the harsh conditions could pose a
drawback for its implementation because of, for example, the
high capital investments required. Another procedure is a one-
pot conversion of carboxylic acids into nitriles.[13] However, this
procedure did not work for small polar molecules, such as suc-
cinic and glutamic acid, and it had additional drawbacks, such
as the stoichiometric use of the hazardous reagent diphospho-
rus tetraiodide. Because glutamic acid and glutamine are abun-
dantly present in the biofuel production as low-value by-prod-
ucts, such as vinasse, distillers grains with solubles, and natural
oil meal,[4] we approached the synthesis of biobased succinoni-
trile, starting from glutamic acid or glutamine and continuing
via the intermediate 3-cyanopropanoic amide (CPAm,
Scheme 1). Previous research showed that g-aminobutyric acid
(GABA) readily cyclized, thereby forming the very stable lactam
2-pyrrolidone.[6] 3-Cyanopropanoic amide cannot cyclize to
form a lactam, and is, therefore, a more promising intermedi-
ate than GABA in the synthesis of linear molecules, such as
succinonitrile.
The goal of this paper is the investigation of the synthetic
route of biobased succinonitrile from either glutamine or glu-
tamic acid. The first part describes the synthesis of 3-cyanopro-
panoic amide from glutamine and glutamic acid, whereas the
second part describes the synthesis of succinonitrile from 3-cy-
anopropanoic amide. Once succinonitrile is formed, it can be
hydrogenated to form DAB. This step is already a commercial
process implemented by the DSM company.[14]
[a] T. M. Lammens, Dr. J. Le Nꢀtre, Dr. E. L. Scott, Prof. J. P. M. Sanders
Valorisation of Plant Production Chains, Wageningen University
PO Box 17, 6700 AA Wageningen (The Netherlands)
Fax: (+31)317 483011
E-mail: tijs.lammens@wur.nl
elinor.scott@wur.nl
[b] Dr. M. C. R. Franssen
Laboratory of Organic Chemistry, Wageningen University
Dreijenplein 8, 6703 HB, Wageningen (The Netherlands)
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T. M. Lammens, E. L. Scott et al.
aqueous ammonia to form 3-cyanopropanoic amide. As the
first step was described in literature as being a facile proce-
dure, giving a yield of 95%,[16] only the second and third steps
in the synthesis, starting from the commercially available Glu-
Me, were investigated for this paper.
3-Cyanopropanoic amide could be prepared from both, glu-
tamine and Glu-Me (Table 1). The yield achieved by starting
from glutamine (56 mol%) was significantly lower than that re-
alized by starting from Glu-Me (86 mol%). Moreover, CPAm is
difficult to extract from the reaction mixture, so an isolated
and purified yield could not be obtained if glutamine was
used as the starting material. To determine the crude yield of
the reaction with glutamine, the reaction was performed in
D2O in the presence of an internal standard. Then, the reaction
1
progress was monitored by using H NMR spectroscopy. After
45 min, glutamine was fully converted into three products. The
main product (56 mol%) was the desired 3-cyanopropanoic
amide, the two by-products were 4-oxo-butyramide and suc-
cinic acid. Scheme 2 illustrates a probable route for the forma-
tion of the by-products. The formation of 4-oxo-butyramide
was the result of the hydrolysis of the imine that was formed
as an intermediate in the oxidative decarboxylation of gluta-
mine. Presumably, the carboxamide group in the glutamine de-
rivative assisted in the hydrolysis of the imine: if the reaction
was performed by using Glu-Me instead of glutamine, 4-oxo-
butyramide was observed in much smaller amounts. Oxidation
of 4-oxobutyramide could result in succinic acid monoamide,
but this compound was not detected in the reaction mixture.
Apparently, hydrolysis of succinic acid monoamide to succinic
acid occurred readily under the applied conditions. Decreasing
the reaction time had a positive influence on the 3-cyanopro-
panoic amide yield, as the formation of by-products was re-
duced. However, 56 mol% was the highest achievable yield.
Starting from Glu-Me, CPA-Me was synthesized in a crude
yield of 86 mol%, with 5 mol% of 4-oxo-butanoic acid methyl
ester present as a by-product. Addition of aqueous ammonia
to this crude product gave a quantitative formation of 3-cya-
nopropanoic amide, which could be purified using recrystalli-
zation. Thus, the more preferable way to synthesize CPAm in
the laboratory is by starting with Glu-Me rather than with glu-
tamine, as the intermediate CPA-Me can be more easily ex-
tracted from the aqueous solution. This is not the case for
CPAm, which is highly soluble in water. Isolation of 3-cyanopro-
panoic amide from the aqueous ammonia solution can be
achieved by simply evaporating the solution to dryness. In an
industrial setting, the additional reaction steps and unit opera-
tions required for glutamic acid as the starting material might
be a drawback and glutamine could be the more suitable start-
ing material. However, in that
Scheme 1. A new route to biobased succinonitrile, starting from either glu-
tamic acid or glutamine.
Results and Discussion
Synthesis of 3-cyanopropanoic amide
Le Nꢁtre et al. previously showed that glutamic acid can be ox-
idatively decarboxylated to 3-cyanopropanoic acid by using
sodium hypochlorite in the presence of a catalytic amount of
sodium bromide.[7] Starting from glutamine, CPAm could be
prepared directly by performing the same reaction. However, if
starting from glutamic acid, three steps are required to prepare
CPAm, as is shown in Scheme 1: 1) esterification of the g-car-
boxylic acid group by using methanol to form glutamic acid 5-
methyl ester (Glu-Me),[15,16] 2) oxidative decarboxylation of the
a-carboxylic acid group to form 3-cyanopropanoic acid methyl
ester (CPA-Me), and 3) amidation of the ester group by using
case, the isolation of 3-cyano-
propanoic amide from the
Table 1. Yields of CPAm, starting from glutamine and Glu-Me, respectively.
aqueous chloride solution as
Starting material
Reaction conditions
CPAm yield [mol%]
well as the selectivity will have
Crude
Purified
to be improved. Also, isolation
of glutamine from plant pro-
teins is more difficult, because
the typically applied conditions
Glutamine
Glu-Me
0.57m in D2O, 3 eq. NaOCl, 10 mol% NaBr, 48C, 45 min.
A) 0.50m in H2O, 3 eq. NaOCl, 10 mol% NaBr, 48C, 45 min.
B) 2 eq. NH4OH, 258C, 75 min.
56
86
n.d.
78
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Synthesis of Biobased Succinonitrile
Succinonitrile synthesis by
water transfer
Different reports revealed that
primary amides could also be
catalytically dehydrated in the
presence of acetonitrile and
water. Water was transferred
from the amide to acetonitrile,
thereby forming acetamide and
the corresponding nitrile.[20–22]
Using this reaction, stoichiomet-
ric amounts of the by-product
acetamide
were
produced.
However, this does not pose a
drawback, as acetamide is com-
mercially produced through hy-
drolysis of acetonitrile.[23] Conse-
Scheme 2. By-product formation in the oxidative decarboxylation reaction of glutamine.
in protein hydrolysis (i.e., heating in the presence of a strong
acid) will also hydrolyze glutamine to glutamic acid.
quently, under these reaction conditions, two chemical prod-
ucts were simultaneously produced, as shown in Scheme 3.
The authors recognize that the use of stoichiometric
amounts of sodium hypochlorite for this reaction makes it diffi-
cult to qualify this part of the procedure as sustainable. Con-
sidering, however, the effort currently directed toward the de-
velopment of more suitable oxidants, such as oxygen, we be-
lieve that further improvement of this part of the procedure
might be very well possible, for example by using haloperoxi-
dase enzymes or mimics thereof.[17] This will be the subject of
further research.
Succinonitrile synthesis by dehydration
The dehydration of 3-cyanopropanoic amide to form succino-
nitrile was investigated for various conditions. To achieve dehy-
dration, the most preferable way would be to use a catalytic
system as opposed to traditional dehydrating agents, such as
phosphorous pentoxide and thionyl chloride,[18] which gener-
ate stoichiometric amounts of waste salts. A method for the
dehydration of primary amides (both aromatic and aliphatic)
was reported by Ishihara et al.[19] The method was based on
rhenium(VII) oxo complexes, for example, perrhenic acid. These
complexes catalyzed the dehydration of primary amides by re-
fluxing in toluene and simultaneously removing water in a
Dean–Stark apparatus. In this case, no by-product was formed.
The solubility of 3-cyanopropanoic amide proved to be a se-
rious issue in applying this system. CPAm has a poor solubility
in apolar solvents, such as toluene and mesitylene, and is only
partly soluble in the more polar dioxane. However, the per-
rhenic acid-catalyzed dehydration reaction, progressed much
less, if at all, in polar solvents, such as dioxane.[19] Therefore,
different solvents were tested: toluene, anisole, dioxane, aceto-
nitrile, and N-methylpyrrolidone. These solvents provided a
yield in the range of 0 to 6%. Dioxane provided the best bal-
ance between CPAm solubility and catalyst activity, but yielded
only 6 mol% succinonitrile.
Scheme 3. Water transfer reaction involving 3-cyanopropanoic amide and
acetonitrile. Reaction of 3-cyanopropanoic amide (middle) with acetonitrile
results in the desired succinonitrile (bottom). Reaction of 3-cyanopropanoic
amide with acetamide leads to undesired succinamide (top).
Considering the large difference in polarity, separation of the
two products would not be very difficult in an industrial set-
ting. Succinonitrile is very well soluble in an organic solvent,
such as ethyl acetate, and can be extracted from an aqueous
solution, whereas acetamide cannot be extracted. After extrac-
tion of succinonitrile, acetamide could be isolated from the
aqueous phase using crystallization.
The yields for preparing succinonitrile using various reaction
conditions are summarized in Table 2. Apparently, palladium(II)
catalyzed the dehydration of 3-cyanopropanoic amide to succi-
nonitrile, whereas the dehydration did not occur by using
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T. M. Lammens, E. L. Scott et al.
pure succinonitrile. This seems to be a rather poor yield; on
the other hand, a high selectivity was achieved. Therefore, the
poor yield is attributed to the equilibrium, and not because of
the formation of other products than succinonitrile. According
to a thermodynamic calculation at the B3LYP/6-311++G(d,p)
level, this system had a slightly positive Gibbs free energy of
reaction, resulting in an unfavorable reaction equilibrium for
the formation of succinonitrile. Increasing the amount of ace-
tonitrile would lead to a higher yield of the desired product,
but it would also dilute the reaction mixture. Therefore, it
seems more economical to separate the product from the re-
action mixture and to recycle the remaining substrate than to
increase the amount of acetonitrile.
Table 2. Activity of different catalysts in the water transfer reaction of
CPAm with acetonitrile.
Catalyst
PdCl2
Reaction conditions
Succinonitrile yield [mol%]
258C, 18 h, MeCN/H2O (1:1)
59
48
3
Pd(OAc)2 258C, 18 h, MeCN/H2O (1:1)
Pd(OH)2/C 258C, 18 h, MeCN/H2O (1:1)
Pd(OH)2/C Reflux, 18 h, MeCN/H2O (1:1)
9
ZnCl2
ZnCl2
ZnCl2
258C, 18 h, MeCN/H2O (1:1)
Reflux, 18 h, MeCN/H2O (1:1)
MW 450 W, 120 s, MeCN/H2O (1:1)
0
0
0
zinc(II) and formaldehyde, although they were reported to cat-
alyze this reaction in the presence of other substrates.[21,22] Im-
mobilized palladium(II), in the form of palladium(II) hydroxide
on carbon, catalyzed this reaction as well, but the succinoni-
trile yield was much lower. Mass-transfer limitations could play
a role here, as the yield increased threefold under reflux condi-
tions, as compared to the reaction at room temperature. Palla-
dium chloride afforded the highest succinonitrile yield
(59 mol%).
The difference in polarity could provide a means to shift the
equilibrium to the formation of succinonitrile. Extraction of
succinonitrile in a biphasic system, with diethyl ether as one
phase and a water–acetonitrile mixture as the other, could
lead to a higher conversion of 3-cyanopropanoic amide.
Figure 2 shows the cumulative amounts of succinonitrile, 3-cy-
The development of the palladium chloride-catalyzed con-
version of 3-cyanopropanoic amide to succinonitrile with time,
1
as tracked by using H NMR spectroscopy in a 1:1 (v/v) mixture
of deuterated acetonitrile and deuterated water, is shown in
Figure 1 and compared to the isolated yields of succinonitrile
Figure 2. Cumulative amounts of succinonitrile (SucCN), 3-cyanopropanoic
amide (CPAM), and succinamide (SucAM) isolated after four reaction cycles.
Note: fresh 3-cyanopropanoic amide was added to the reaction mixture
after each cycle, to compensate for the loss caused by the partial extraction
of 3-cyanopropanoic amide along with succinonitrile. Therefore, the sum of
the cumulative amounts exceeds 100%.
anopropanoic amide, and succinamide over four reaction
cycles. The yield of succinonitrile after the first cycle was
53 mol%, which was the same as in a single phase system.
This indicates that the equilibrium was not shifted toward suc-
cinonitrile formation in the biphasic system, but remained con-
stant. After the second and third reaction cycles, the cumula-
tive succinonitrile yield increased to a final value of 74 mol%,
after which no further increase was observed. However, the
succinamide yield increased significantly, even after the fourth
cycle. This is probably attributable to an accumulation of acet-
amide in the aqueous phase (acetamide cannot be extracted
from an aqueous phase by using diethyl ether), which shifts
the equilibrium further to the top in Scheme 3 and even leads
to the uptake of one molecule of water by the starting materi-
al, 3-cyanopropanoic amide.
Figure 1. Variation of relative amounts of succinonitrile (SucCN) and 3-cyano-
propanoic amide (CPAM) in the reaction mixture with time, as detected by
1
applying direct H NMR spectroscopy to the reaction mixture (straight lines),
and the crude yields detected after extraction of the products from the reac-
tion mixture (dotted lines).
and 3-cyanopropanoic amide. All of the succinonitrile could be
extracted from the aqueous phase, but not all of CPAm. This
was expected because CPAm is much more polar than succino-
nitrile. Figure 1 further demonstrates that the steady state of
the reaction was reached after approximately 5 hours, at 38
and 62 mol% of 3-cyanopropanoic amide and succinonitrile,
respectively. Besides 3-cyanopropanoic amide and succinoni-
trile, traces of succinamide (<1 mol%) and acetamide (mostly
present as deuterated acetamide) were detected as the only
other compounds present in the reaction mixture, indicating
that no other by-products were formed. Scaling the reaction to
a gram scale and purifying the crude products by using
column chromatography gave an isolated yield of 41 mol%
To improve the economic feasibility of palladium-based cata-
lysts applied in an industrial production of succinonitrile, the
amount of catalyst used should be less than the 10 mol% al-
ready reported in literature.[20] The current market price of pal-
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Synthesis of Biobased Succinonitrile
ladium is approximately 19000 EkgÀ1 [24]
,
whereas the market
11 mol%. No palladium(II) was found in the organic phase
after extraction, indicating that the catalyst could be recycled
efficiently. A reason for the lower yield could be the less favor-
able reaction conditions, owed to the use of a heterogeneous
instead of a homogeneous system. If acetonitrile would
become the water acceptor of choice, it should be biobased as
well. This is expected to be possible by oxidative decarboxyla-
tion of the amino acid alanine, which will be the subject of fur-
ther research. Accordingly, this route would not only yield bio-
based succinonitrile, but also biobased acetamide.
price of succinonitrile would probably be similar to that of cap-
rolactam, which is currently 2 EkgÀ1.[25] As palladium is about
ten thousand times more expensive than succinonitrile, the
palladium loading of the reactor should either be very low, or
the palladium should be recycled in the process. Figure 3
Conclusions
The goal of this paper was to investigate the possibility to syn-
thesize succinonitrile from glutamic acid to be able to produce
biobased 1,4-diaminobutane. This conversion was shown to be
feasible. The first step was either an oxidative decarboxylation
of the 5-methyl ester of glutamic acid, followed by an amida-
tion of the crude product, or an oxidative decarboxylation of
glutamine. In both cases, the product was 3-cyanopropanoic
amide. CPAm was synthesized from Glu-Me in a crude yield
above 86 mol%. In the second step, CPAm can be dehydrated
to yield succinonitrile. The most effective method to achieve
this was a palladium(II)-catalyzed water transfer reaction in the
presence of acetonitrile as the water acceptor. Under the em-
ployed conditions, no significant amounts of by-products were
found, indicating that, although the conversion yield of 3-cya-
nopropanoic amide to succinonitrile was only 62%, the selec-
tivity of this reaction was close to 100%.
Figure 3. Crude yield of succinonitrile as a function of the amount of catalyst
employed. Conditions: 18 h, 258C.
shows succinonitrile yields at various amounts of palladium
chloride loadings. The succinonitrile yield achieved by using
0.01 mol% palladium chloride was less than 1 mol%. There-
fore, catalyst recycling will be required for a commercial appli-
cation of this process. There are a number of reports about re-
cycling or immobilizing a homogeneous, palladium(II)-based
catalyst, for example on silica,[26] polymeric resins,[27] polyethy-
lene glycol,[28] or on paramagnetic nanoparticles.[29] In most
cases, the immobilization was based on palladium–phosphine
interactions, such as the immobilization on silica reported by
Van Koten et al.[26] Although the exact mechanism of the cur-
rent reaction was not fully investigated,[20] it is likely that the
coordination of acetonitrile to palladium(II) played a crucial
role, as the Lewis acidity of zinc chloride alone was not suffi-
cient to promote the reaction (Table 2). This was supported by
our observation that the addition of two equivalents of a tri-
phenylphosphine sulfonate (TPPS) ligand to the palladium
chloride solution (before adding the substrate) resulted in no
formation of succinonitrile. TPPS ligands are known to interact
strongly with transition metals, such as palladium,[30] and in
this case, the ligands probably displaced the coordinated ace-
tonitrile from the active palladium, thus forming an inactive
species. This eliminated the possibility to use the palladium–
phosphine interaction for the immobilization of the catalyst on
a supporting material or for the entrapment in the aqueous
phase. Therefore, a supported palladium(II) species, to which
acetonitrile could still coordinate, would be the preferred cata-
lyst for an industrial application of this reaction.
It is still necessary to establish an effective method to recy-
cle the palladium, to find a greener oxidant than hypochlorite,
and to design a process for the isolation of glutamic acid or
glutamine from agricultural by-product streams. But if these re-
quirements are met, this biobased route will be a good alter-
native to the fossil-based route for the production of succino-
nitrile.
Experimental Section
Materials and equipment
l-Glutamic acid (>99.5%), l-glutamic acid 5-methyl ester (Glu-Me,
99%), l-glutamine (99%), sodium bromide (>99%), palladium
chloride (99.99%), palladium acetate (99.99%), palladium hydrox-
ide (20 wt% loading on carbon), triphenylphosphine sulfonate (>
90%), zinc chloride (98%), paraformaldehyde (>95%), formic acid
(>98%), polyacrylonitrile (Mw =150000), perrhenic acid (99.99%,
65–70 wt%, aq.), sodium hypochlorite (RG, 10–15 wt%, aq.), and
ammonium hydroxide (puriss., 30–33 wt% ammonia in water)
were all purchased from Sigma–Aldrich. All organic solvents were
of analytical grade and used as received. High resolution MS spec-
tra were recorded on an Exactive apparatus from Thermo Scientific,
equipped with a DART probe. Spectra were recorded in the posi-
tive mode. M/z ratios were detected from 50 to 500. NMR spectra
were recorded by using a Varian 400 MHz NMR spectrometer.
Another approach to the recycling of the catalyst would be
to use a water acceptor different from acetonitrile. An experi-
ment comprised of a suspension of poly(acrylonitrile) in water,
rather than a 1:1 mixture of acetonitrile and water, was per-
formed, for which succinonitrile was also found as the sole
product. Under the same conditions as for the acetonitrile
system, the succinonitrile yield achieved in this case was
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T. M. Lammens, E. L. Scott et al.
(400 MHz) spectroscopy to determine the crude succinonitrile
Oxidative decarboxylation of Glu-Me to CPA-Me
yield.
In a typical experiment, a round-bottomed flask was filled with
Glu-Me (6.0 g, 37 mmol), NaBr (0.38 g, 3.7 mmol), and 75 mL water.
The flask was placed in an ice bath, and NaOCl (15 wt%, aq.;
45 mL, 111 mmol) was added slowly while stirring vigorously. After
30 min, the ice bath was removed, and the reaction was quenched
by using Na2S2O3 after a further 15 min. The solution was then sa-
turated by using NaCl, and 3-cyanopropanoic acid methyl ester
(CPA-Me) was extracted by using diethyl ether (4ꢅ125 mL). The or-
ganic fractions were combined and dried by using MgSO4. After fil-
tration, the solvent was removed under reduced pressure, yielding
CPA-Me as a yellowish liquid (3.81 g), which was not purified. The
product was analyzed by using 1H and 13C NMR spectroscopy to
PdCl2-catalyzed dehydration of CPAm to succinonitrile
In a typical experiment, a round-bottomed flask was filled with
PdCl2 (17.7 mg, 0.10 mmol), CPAm (98.1 mg, 1.0 mmol), and 6 mL
of a 1:1 (v/v) mixture of water and acetonitrile. The reaction mix-
ture was stirred for 6 h under a nitrogen atmosphere. Subsequent-
ly, succinonitrile was extracted from the reaction mixture by using
dichloromethane and then diethyl ether (3ꢅ6 mL in both cases).
The organic fractions were combined, dried over MgSO4, filtered,
and the solvent was evaporated under reduced pressure. The
1
crude product was analyzed by using H and 13C NMR (400 MHz)
1
determine the crude CPA-Me yield (>84 mol%). H NMR (400 MHz,
[D6]DMSO): d=3.64 (s, 3H), 2.69 ppm (m, 4H); 13C NMR (400 MHz,
[D6]DMSO): d=171.1, 119.8, 51.7, 29.0, 12.4 ppm.
spectroscopy to determine the crude succinonitrile yield (typically
50–60 mol%). The crude product could be purified by using
column chromatography, with diethyl ether as the mobile phase.
Retention factors for CPAm and succinonitrile on TLC with diethyl
ether were 0.1 and 0.7, respectively. H NMR (400 MHz, CDCl3): d=
2.79 ppm (s, 4H); 13C NMR (400 MHz, CDCl3): d=116.5, 14.7 ppm.
1
Oxidative decarboxylation of glutamine to CPAm
In a typical experiment, a round-bottomed flask was filled with l-
glutamine (146 mg, 1 mmol), NaBr (10.3 mg, 0.1 mmol), and di-
glyme (IS, 33.6 mg, 0.25 mmol) in 1.75 mL D2O. The flask was
placed in an ice bath, and NaOCl (15 wt%, aq.; 1.25 mL, 3 mmol)
was added slowly while stirring vigorously. After 30 min, the ice
bath was removed, and the reaction was quenched by using
+
MS for succinonitrile +NH4 (C4H8N3): m/z: calcd. 98.07182, found
98.07149.
For the experiment with polyacrylonitrile, a round-bottomed flask
was filled with PdCl2 (17.7 mg, 0.10 mmol), polyacrylonitrile (0.50 g,
10 mmol CN), water (3 mL), and CPAm (98.1 mg, 1.0 mmol). The re-
action mixture was stirred for 18 h, after which the product was ex-
tracted by using diethyl ether (3ꢅ6 mL). The remainder of the pro-
cedure was identical to that directly above. Polyacrylonitrile could
be separated from the aqueous phase by using filtration through a
0.2 mm filter.
1
Na2S2O3 after another 15 min. An H NMR spectrum of the reaction
mixture was recorded, and the relative amount of 3-cyanopropano-
ic amide was determined by using the internal standard diglyme.
1
3-Cyanopropanoic amide (CPAm): H NMR (400 MHz, D2O): d=3.04
1
(m, 2H), 2.99 ppm (m, 2H); Diglyme: H NMR (400 MHz, D2O): d=
3.95 (m, 4H), 3.90 (m, 4H), 3.66 ppm (s, 6H).
ZnCl2-catalyzed dehydration of 3-cyanopropanoic amide to
succinonitrile
Amidation of CPA-Me to CPAm
In a typical experiment (performed in a well-ventilated fume hood,
as there was a risk of hydrogen cyanide formation), a round-bot-
tomed flask was filled with unpurified CPA-Me (3.81 g, from the ox-
idative decarboxylation of Glu-Me), to which NH4OH (30–33 wt%,
aq.; 10 mL, ꢀ75 mmol) was added slowly while stirring. Then the
flask was closed and left at room temperature for 75 min, after
which the reaction mixture was dried at 658C under reduced pres-
sure, yielding CPAm (3.33 g, >86 mol% yield from Glu-Me; >95%
An Ace pressure tube was filled with ZnCl2 (0.136 g, 1.0 mmol),
CPAm (98.1 mg, 1.0 mmol), and 1 mL of a 1:1 (v/v) mixture of
water and acetonitrile. The reaction mixture was irradiated at
450 W in a microwave oven for 2 min and then cooled to room
temperature. Succinonitrile was extracted by using dichlorome-
thane (2ꢅ5 mL). The organic fractions were combined, dried over
MgSO4, filtered, and the solvent was evaporated under reduced
pressure. The crude product was analyzed by using 1H and
13C NMR (400 MHz) spectroscopy to determine the crude succino-
nitrile yield.
1
purity according to H NMR spectroscopy) as an orange solid. Re-
crystallization of the crude CPAm from ethyl acetate[31] afforded an-
alytically pure CPAm (2.86 g, 29 mmol, 78 mol% yield from Glu-Me;
purity according to 1H and 13C NMR spectroscopy), as a white
powder. For further experiments, the purified CPAm was used.
1H NMR (400 MHz, [D6]DMSO): d=7.43 (s, 1H), 6.98 (s, 1H), 2.60 (t,
2H), 2.40 ppm (t, 2H); 13C NMR (400 MHz, [D6]DMSO): d=171.1,
Acknowledgements
+
120.3, 30.2, 12.4 ppm. MS of 3-cyanopropanoic amide +NH4
(C4H10ON3): m/z: calcd. 116.08239, found 116.08182.
The authors wish to thank Barend van Lagen for performing
NMR measurements, Frank Claassen for the MS measurements,
and Satesh Gangarapu for performing the Gibbs free energy of
reaction calculations. Further, we are grateful toNWO-Aspect for
funding of this work.
Perrhenic acid-catalyzed dehydration of CPAm to succinoni-
trile
A round-bottomed flask was filled with CPAm (98.1 mg, 1.0 mmol),
1,4-dioxane (10 mL), and (HO)ReO3 (120 mg, 0.3 mmol). The flask
was equipped with a Soxhlet apparatus filled with molecular sieves
(3 ꢆ, activated overnight at 2208C) and refluxed under a nitrogen
atmosphere for 22 h. Afterwards, the solution was cooled to room
temperature, the solvent was removed under reduced pressure,
and the crude product was analyzed by using 1H and 13C NMR
Keywords: biomass
resources · waste prevention
· catalysis · palladium · renewable
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