Cis, cis -Muconic acid isomerization and catalytic conversion to biobased cyclic-C6-1,4-diacid monomers

Article abstract of DOI:10.1039/c7gc00658f

Renewable terephthalic and 1,4-cyclohexanedicarboxylic acids can be produced from biomass via muconic acid using a combination of biological and chemical processes. In this conversion scheme, cis,cis-mucononic acid is first obtained by fermentation using

Full text of DOI:10.1039/c7gc00658f

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PAPER
cis,cis-Muconic acid isomerization and catalytic conversion to
biobased cyclic-C6-1,4-diacid monomers
Received 00th January 20xx,
Accepted 00th January 20xx
Jack M. Carraher,a,b Toni Pfennig,a,b Radhika Giri Rao,a,b Brent H. Shanks,a,b and Jean-Philippe
Tessonnier*,a,b
DOI: 10.1039/x0xx00000x
Renewable terephthalic and 1,4-cyclohexanedicarboxylic acids can be produced from biomass via muconic acid using a
combination of biological and chemical processes. In this conversion scheme, cis,cis-mucononic acid is first obtained by
fermentation using either sugar or lignin monomers as a feedstock. The diunsaturated cis,cis-diacid is then isomerized to
trans,trans-muconic acid, reacted with biobased ethylene through Diels-Alder cycloaddition, and further hydrogenated or
dehydrogenated to yield the desired 100 % renewable cyclic dicarboxylic acid. The isomerization of cis,cis- to trans,trans-
muconic acid represents the main bottleneck in this process due to undesired side reactions that promote ring closing to
form lactones. Therefore, new technologies for the selective isomerization of muconic acid are urgently needed. Here, we
studied the corresponding reaction kinetics to elucidate the mechanisms involved in both the isomerization and cyclization
reactions with the objective to identify conditions that favor the selective formation of trans,trans-muconic acid. We
demonstrate that the reactivity of muconic acid in aqueous media strongly depends on pH. Under alkaline conditions,
cis,cis-muconic acid is deprotonated to the corresponding muconate dianion. This species is stable for extended periods of
time and does not isomerize. Conversely, cis,cis-muconic acid readily isomerizes to its cis,trans-isomer under acidic
conditions. Prolonged heating further triggers the intramolecular cyclizations through reaction of the carboxylic acid and
alkene functionalities. The formation of the muconolactone and its dilactone is kinetically favored over the isomerization
to trans,trans-muconic acid over a broad range of conditions. However, strategies involving the chelation of the
carboxylates with inorganic salts or their solvation using polar aprotic solvents were found to hamper the ring closing
reactions and allow the isomerization to trans,trans-muconic acid to proceed with high selectivity (88 %). The obtained
compound was further reacted with ethylene and hydrogenated to 1,4-cyclohexanedicarboxylic acid, an important
monomer for the polyester and polyamide industries.
www.rsc.org/
However, oxidation-free routes through muconic acid (MA), a
platform intermediate from sugar and lignin fermentation,13-19
have also emerged (Scheme 1b). The MA route can be
Introduction
Diacid monomers are central to the production of commodity
polyamides and polyesters, a $118bn market1-3 with ties to the
packaging and bottling, textiles, and automotive industries,
among others.4 While these building blocks are typically
manufactured from petroleum, the demand for renewable
diacid monomers is increasing as a result of the growing
number of environmentally-conscious end users.4-9 Significant
efforts are, therefore, being dedicated to developing new
processes to address this need. In the case of terephthalic acid
(TPA), the common approach targets renewable p-xylene as a
drop-in for oxidation in the AMOCO process (Scheme 1a).10-12
considered advantageous as this intermediate can be
converted to a variety of commodity and specialty chemicals,
19, 20
5, 21
including adipic acid,14,
TPA,4,
and 1,4-
cyclohexanedicarboxylic acid (CHDA).21
To access the cyclic products, MA is converted to 1,4-
cyclohex-1/2-enedicarboxylic acid through Diels-Alder
cycloaddition with ethylene, followed by dehydrogenation to
TPA or hydrogenation to CHDA.4, 5, 21-25 So far, these research
efforts have focused on the downstream conversion of the
Diels-Alder active trans,trans-MA (ttMA) isomer. However, the
preparation of cyclic diacids requires an additional MA
isomerization step that has received little attention so far.
There exists a significant gap in the literature with respect to
isomerization of biologically-produced cis,cis-MA (ccMA) to
Diels-Alder active ttMA.
While conceptually simple, the isomerization of MA to its
tt- isomer was not reported until seven decades after the
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in an effort to understand the driving forces behind these
reactions. Herein are described the spontaneous reactions of
cc- and ctMA and the production of cyclic diacid monomers
utilizing two new isomerization technologies directly resulting
from this mechanistic study.
Results and discussion
A preliminary investigation of MA isomerization was carried
out in which solutions containing 4.8 mM ccMA and 1.5 mM
acetic acid (AA, used here as an internal standard) were
heated to 75.5 ± 0.5 °C and monitored in situ by 1H NMR
(Fig. 1). Signals corresponding to ccMA (7.61 (2H) and 6.08
ppm (2H)) were consumed within approximately 20 minutes.
Simultaneously, new signals (8.15, 6.82, 6.25, and 6.11 ppm, all
1H) corresponding to ctMA were observed. Further heating
resulted in the loss of ctMA signals on significantly longer time
scales, and the formation of singlets (7.83, 6.24, and 5.58 ppm,
each 1H) and a pair of signals at 2.97 and 2.74 ppm (each 1H)
attributed to muconolactone (Mlac). The pair of Mlac signals
integrated to a single proton due to the incorporation of a
solvent deuterium resulting in an undetectable signal (vide
infra). Prolonged heating resulted in the appearance of two
additional signals at 5.47 ppm (2H) and a pair of signals at 3.16
and 2.98 ppm (2H, 2H + 2D) assigned to tetrahydrofuro[3,2-
b]furan-2,5-dione (Lac2).
Scheme 1. (a) Production of renewable terephthalic acid and its derivative dimethyl
terephthalate (TPA) through stepwise oxidation of biobased p-xylene in the AMOCO
process. Further hydrogenation yields the corresponding dimethyl 1,4-
cyclohexanedicarboxylate. (b) Production of TPA and 1,4-cyclohexanedicarboxylic acid
(CHDA) by isomerization of cis,cis- to trans,trans-MA, followed by Diels-Alder
cycloaddition of ethylene, and de/hydrogenation.
initial publications on MA reactivity.26-28 It was in 1936 that the
photocatalytic isomerization of MA in the presence of I2 was
described by Grundmann.29 Still, two more decades passed
until Elvidge et al. contributed a significant amount of work30-36
providing the first definitive identification of the much
anticipated intermediate cis,trans-MA.37 Following this
pioneering work, it took another half century until Drath’s
corporation patented isomerization technologies utilizing
catalysts such as Pd/C, and I2 in acetonitrile under reflux or
irradiation with UV light.4, 21, 23, 38-40 These findings, however,
were not sufficient to propel the technology into the industrial
realm. While noble metals are excellent de/hydrogenation
catalysts, their high cost and relatively low selectivity in the
isomerization to ttMA makes them less attractive for this step.
Likewise, restrictions placed on the I2 system, e.g. limiting feed
solutions to 10 wt % MA, place serious economic constraints
on the process. Finally, the low profit margins for high-volume-
low-value chemicals like TPA only underscored these
limitations.4 Conversely, low-volume-high-value chemicals like
CHDA ($5,000–10,000/ton vs. $1,200/ton for TPA) would be
more attractive. It would therefore be beneficial to the
production of both TPA and CHDA to revisit the MA
isomerization and develop green technologies for the
economic production of ttMA.
Under these experimental conditions Mlac and Lac2 were
found to be in equilibrium with the constant K75 = 0.375
°C
(Fig. S1). These results revealed that the ring closing reactions
are favoured over isomerization for ctMA. ttMA was not
observed, which is consistent with the literature.4,
22-25, 37
A
decrease in the amount of total signal as a function of time
was observed and was attributed to the progressive
incorporation of deuterium upon reversible lactonization to
both Mlac and Lac2. This phenomenon is illustrated in Scheme
S1. Kinetic traces for consumption of ccMA and ctMA fit first
order rate equations (eq 1a), where [ccMA]t = concentration of
ccMA at time t, [ccMA]∞ = concentration at time infinity,
To address this challenge, we chose to investigate the
driving forces behind the spontaneous lactonisation of this
molecule. This prompted us to seek
a more in-depth
Figure 1. 1H NMR spectra of muconic acid isomers (D2O, 600 MHz, room temperature)
with acetic acid internal standard (2.07 ppm). The large signal at 4.78 ppm is due to the
solvent. Spectra are listed from bottom to top by increasing time intervals at 75 ˚C (t =
0, 0.5, 5, and 55 hours).
understanding of MA’s chemistry and gather insights that will
facilitate new catalytic and non-catalytic isomerization routes.
The current work is
a mechanistic investigation into
isomerization and lactonization of cc- and ctMA, respectively,
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However, two key irregularities were observed for the further
conversion of ctMA to Mlac and Lac2 (Fig. 2b). First, the
experimentally determined concentrations of Mlac and Lac2
(and consequently [MA]total) deviated from the simulations at
long reaction times. At 50 and 75 °C, this was found to be due
to incorporation of solvent deuterium and loss of proton in the
reversible Mlac/Lac2 equilibrium described above (Scheme
S1). This deviation became more pronounced at 95
°C,
suggesting MA degradation. Second, the simulations deviated
slightly from the experimental results for ctMA consumption at
the beginning and end of the kinetic trace. The deviation at
long reaction times can be accounted for by making
corrections to the experimentally determined concentrations
by the methods outlined in the ESI eqs. S1-S8 and
demonstrated in Figures S2a-d. The latter observation
suggested that pH affects the isomerization greatly, and this
prompted a more in-depth investigation of pH effects on
reaction kinetics.
Scheme 2. Isomerization pathway used in KINSIM simulations shown in Figure 2.
Scheme 2 does not consider pH effects.
∆[ccMA] = [ccMA]o – [ccMA]∞, kobs = observed rate constant
(s-1), and t = time (s). As expected, increasing [MA] had no
effect on kobs, consistent with the isomerization being first
order with respect to [MA]. Kinetic simulations were
performed using KINSIM utilizing the mechanism outlined in
Scheme 2. The fit of simulated to experimental data shown in
Figure 2a for the isomerization of ccMA to ctMA is excellent.
[ccMA]t = [ccMA]∞ + Δ[ccMA] × exp-k
eq 1a
eq 1b
obs × t
ln([ctMA] /[ctMA]o ) = -kobs × t + constant
t
Figure 3. Plots of kobs vs. pH for ccMA, 22.5 °C (top) and ctMA, 90.0 °C (bottom)
conversion. (■) correspond to experimental data points; the line is only meant to guide
the eye.
Figure 2. Experimental (■) and simulated (―) kineꢀc traces for ccMA isomerization at
83 °C (a) and ctMA isomerization at 75 °C (b)
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Effect of pH on reaction kinetics
Kinetic traces obtained over a wide range of pH values (1.7 to
6.5) fit first order rate equations (eq 1a for ccMA and the
linearized form, eq 1b, utilizing the initial rates for ctMA). The
dependence of kobs on pH is shown in Figure 3 for both ccMA
and ctMA conversions. It can be clearly seen that the observed
rate constants were unaffected below pH~2.5, increased
between pH 2.5 and 4 to a maximum, then decreased between
pH 4 and 6.5 to roughly 0 s-1, i.e. no reaction was observed
above pH 7. Figure 3 demonstrates why E. coli and P. Putida
fermentations (typically carried out near neutral pH) report
ccMA as the only isomer present.18, 41
The trend in kobs relative to pH can be explained by the
reactivity of the various protonation states of MA. For
instance, ccMA conversion at 22.5 °C (Fig. 3) occurred with a
rate constant that was independent of pH up to 2.5 which is
consistent with a unimolecular reaction of the fully protonated
state (ccMAH2). Between pH 2.5 and 4 the solution is primarily
a mixture of ccMAH2 and ccMAH-. Above pH 4 the solution is
primarily a mixture of ccMAH- and ccMA2-. Henceforth, the
notation in this article will be MA for discussion of MA
reactivity in general and MAH2, MAH-, and MA2- for specific
Scheme 3 Isomerization pathway accounting for pH effects. At 90 °C (Fig. 3b) the acid
catalysed lactonisation pathway seen at lower temperature (Fig. 4), k2H (red), was not
observed.
protonation states. Scheme
3 was prepared with these
considerations in mind.
This pathway is active at elevated temperatures for reactions
performed below pH 2 but its second order rate constant does
not scale as rapidly with temperature as the unimolecular rate
constant k2a (Table 1). Activation parameters were calculated
for the individual steps with equation 3 and are also shown in
Table 1. No attempt was made to determine the effect of pH
on Mlac/Lac2 equilibrium due to ctMA/Mlac irreversibility.
Scheme
3
was simulated in KINSIM using the
experimentally determined data in Table 1 and estimated
values for parameters that were not directly measurable (eq
S9-11 and Table S1). However, significant deviation of the
model in Scheme 3 was observed for the low pH lactonization
of ctMA at 50 °C (Fig. 4) and 75 °C due to an acid catalysed
lactonization reaction pathway shown in equation 2.
Therefore, values for k2H and k2a were determined in a series of
experiments in which pH was less than 1.5 to ensure ctMAH2
as the primary active species in solution. Plots of kobs vs. [H+]
+
ctMAH2 + H+
Mlac + H
k2H
eq 2
→
ln(k/T) = ln(kB/h) + ∆Sǂ/R – ∆Hǂ/RT
eq 3; where k =
were linear with y-intercept equal to k2a and slope equal to k2H
.
Table 1. Experimentally determined elementary rate constants and activation parameters for Scheme 3a
ccMA-ctMA
∆Hǂ (kj/mol)
∆Sǂ (j/molK)
22.5 °C
50.0 °C
83.3 °C
k1a
k1c
6.5 ± 0.6 × 10-6
9.5 ± 1.0 × 10-5
1.5 ± 0.3 × 10-3
76 ± 1
NR
-88 ± 2
NR
NR
NR
NR
ctMA-Mlac
∆Hǂ (kj/mol)
∆Sǂ (j/molK)
50.0 °C
8.0 ± 1.0 × 10-8
65.0 °C
5.2 ± 0.5 × 10-7
75.0 °C
1.5 ± 0.1 × 10-6
90.0 °C
3 ± 1 × 10-6
NR
k2a
k2c
87 ± 11
NR
-110 ± 34
NR
NR
NR
NR
b
k2H
6.9 ± 0.5 × 10-6
3.8 ± 0.5 × 10-5
9.0 ± 0.9 × 10-5
NR
94 ± 5
-54 ± 13
∆Sǂ (j/molK)
-76 ± 3 d
-56 ± 2 d
-
Mlac-Lac2
∆Hǂ (kj/mol)
98 ± 1 d
102 ± 1 d
-
50.0 °C
1.0 ± 0.1 × 10-7
2.4 ± 0.5 × 10-7
0.417
65.0 °C
75.0 °C
1.5 ± 0.2 × 10-6
4.0 ± 0.8 × 10-6
0.375
95.0 °C
1.5 × 10-5
4.0 × 10-5
0.340
c
k3
-
-
-
c
k-3
c
K3
a Experimentally determined rate constants (s-1) and activation parameters for Scheme 3. Simulated results and estimations for acid dissociation constants
and k1b and k2b are described in the ESI. ‘NR’ denotes ‘no reaction’ (i. e. k = 0), ‘ - ‘ corresponds to experiments that were not carried out under the specified
conditions. b Second order rate constants for acid catalysed reaction (M-1s-1). c Values obtained from preliminary experiments near pH 3. No attempt was
made to investigate pH effects on Mlac – Lac2 equilibrium. d Activation parameters based on experiments near pH 3.
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a resonance structure in which the carboxylates exert an equal
and opposite interaction with their respective γ-C atoms.
Perhaps the lack of ctMA2- reactivity can be explained by DFT
calculations, but this is beyond the scope of the current work.
Like ccMAH2, the kinetic traces for ctMAH2 fit 1st order rate
equations and kobs did not vary with [ctMA], but the entropy of
activation for ctMAH2 lactonization was unusually large and
negative for a unimolecular reaction. This again suggests a
significant contribution from the solvent. It is unclear,
however, if the reaction proceeds through pathway 2a or 2b of
Scheme 5 or in a more concerted mechanism involving solvent
as shown in Scheme 6. Reaction 3 of Scheme 5 may also be
concerted like Scheme 6. Again, differentiation between these
nuances may benefit from modelling by DFT, which is beyond
the scope of the current work.
Though some questions with regard to fine detail remain,
the kinetic behaviour indicates that there are two primary
routes to consider if the goal is to prevent lactonisation and
promote isomerization to ttMA. 1) Choosing a solvent that
destabilizes the lactonisation transition state may promote
ttMA formation. It is also preferable that cc- and ctMA have
relatively high solubility to allow operation at higher reactant
concentration. For this reason, polar solvents were chosen for
the next part of this study (vide infra). Additionally, if Scheme 6
Figure 4. Plot of kobs vs. pH for ctMA conversion at 50.0 ˚C. (■) correspond to
experimental data points; the line is only meant to guide the eye.
elementary rate constant, T = temperature (K), kB = Boltzmann
constant, h = Planck’s constant, ∆Sǂ = entropy of activation,
and ∆Hǂ = enthalpy of activation.
Mechanistic information
The isomerization of ccMAH2 (Scheme 4, reaction 1) appears to
be dominated primarily by steric effects and solvent
interaction with the transition state. Large values for the
entropy of activation (∆Sǂ = -88 j/mol K) are typically observed
in bimolecular reactions, but the isomerization of MA fits first
order rate equations and kobs is unaffected by [ccMA]. It is
therefore reasonable to conclude it to be a unimolecular
reaction.
Solvent
rearrangements
to
facilitate
formation/stabilization of the transition state would explain
the apparent discontinuity between these observations.
At higher pH, between 2.5 and 4, ccMAH2 coexists with
ccMAH-. We found that ccMAH- isomerizes with a rate
constant one order of magnitude larger than that of ccMAH2.
While steric interactions still likely play
a role, the
isomerization appears to be primarily driven by electronic
interactions between the cis-carboxylate and its γ-C (Scheme
4, reaction 2 and Figure 5).
Above pH 4, the solution contains primarily ccMA2-, which
remains stable for extended reaction times. Stabilization of
ccMA2- may be the result of resonance structures (Scheme 4,
reaction 3) in which equal and opposite intramolecular
carboxylate/γ-C interactions stabilize the isomer. While these
interactions appear to be strong enough to stabilize ccMA2-, no
C-O bond formation to produce Mlac and Lac2 was observed.
At no point was isomerization of ctMA to ttMA observed.
Instead, lactonization occurred under all conditions below pH
7. The driving forces for lactone formation appear to be
analogous to those for ccMA isomerization with two
exceptions. First, ctMA ring closes via an acid catalysed
pathway at low temperatures (Scheme 5, reaction 1) in
addition to the unimolecular pathways shown in reactions 2a-
b. Second, the lack of ctMA2- reactivity cannot be explained by
Figure 5. 1H NMR spectra (D2O, 600 MHz) of ccMA (a) and ctMA (b) in the pH range 2 –
7. The large change in chemical shift of the γ-C with pH supports
intramolecular interaction.
a strong
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Scheme 4. Proposed mechanism for isomerization of ccMA at (a) low, (b) middle, and
(c) high pH.
is an accurate representation of the role of water, i.e. proton
exchange is required to facilitate lactonisation, then the
solvent should also be aprotic. 2) The introduction of a species
capable of binding carboxylate functionalities should disrupt
the intramolecular interactions and allow for isomerization to
ttMA as opposed to lactonisation. These hypotheses served as
a basis for the work discussed in the next two sections.
Scheme 5. Ring closing of ctMA to Mlac through acid catalysed reaction (a), and
Isomerization to ttMA in polar aprotic solvents
unimolecular isomerization at low (b), middle (c), and high pH (d).
Results from a solvent screening in which primarily polar
aprotic solvents were tested is summarized in Table 2. Toluene
was the only non-polar solvent chosen in an attempt to
identify the effect of polarity on the transition states in lactone
formation vs. isomerization. This non-polar solvent did not
yield any ttMA. All polar protic solvents yielded Mlac as the
primary product (ttMA selectivity <5 %). This trend would
DMSO is typically considered to be a green solvent.42-44
These results revealed that the role of the solvent is
complex and cannot be simply described in terms of polar vs.
nonpolar or protic vs. aprotic properties. At first glance, one
could conclude that the polarity of the solvent would explain
Mlac vs. ttMA reaction pathways, but if that were the case
support
a lactonisation pathway outlined in Scheme 6.
Noteworthy solvents are triethylamine, acetonitrile, and
DMSO. Triethylamine is the only solvent in which severe
degradation of MA was observed. That is, after 2 weeks at
75 °C no recognizable forms of MA (to include lactones) were
observable. Acetonitrile yielded primarily lactones after 2
weeks. This is noteworthy in that it sheds more light on the
role of the solvent, vide infra. THF and ethyl acetate yielded
some ttMA (<5 %), but mainly formed lactones. DMSO was the
only solvent in which ttMA was a major observable product.
ttMA selectivity was as high as 88 % (62 % conversion) in
DMSO. This observation offers interesting perspectives as
Scheme 6. Possible solvent interaction facilitating lactonisation of ctMAH2.
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then toluene would be expected to yield ttMA, which it does
not. Likewise, if it were a question of the solvents ability to
donate/accept protons, then one would anticipate ttMA
formation in acetonitrile. However, while acetonitrile is
relatively polar and lacks the ability to donate protons,
lactonisation dominates with no traces of ttMA. An
investigation into the effects of solvent polarity on the
molecular orbitals of ctMA and relative proton donating ability
may provide useful insights into this phenomenon.
Isomerization to ttMA with inorganic salts
The above results suggest that successful isomerization to
ttMA can be achieved by introducing a species that can bind
the carboxylate and therefore minimize the intramolecular
interactions that ultimately lead to lactonisation, specifically
from ctMAH-. An obvious choice would be to operate at
conditions under which the acids remain protonated. This
would allow competition between Mlac and ttMA reaction
pathways (Mlac has been shown to be unimolecular, ttMA is
assumed unimolecular based on cc- and ctMA reaction
pathways). However, the existence of the acid catalysed
lactonisation pathway makes this route unfeasible as a low pH
would be required. Additionally, no ttMA was observed at 90
Figure 6. 1H NMR (600 MHz, D2O) spectra of 5.1 mM cc- & ctMA with 450 mM La(OH)3
adjusted to pD = 4.45 with HNO3 (top) was heated to 90 °C for 4 days (bottom).
ctMA, and the remaining 20 % were unidentified byproducts.
Yields up to 55 % (60 % selectivity) were observed after 10.5
days at 75 °C. The selectivity varied widely with pH; up to 85 %
near pH 5. At low pH (< 3) MA is present in the form MAH2,
3+
which does not form a complex with Laaq as well as MAH-
+(3-n)
would. At high pH (> 5.5) La(OH)n
species form; these
-
species have a lower affinity for RCO2 and also lower
+(3-n-x)
solubility. Between these extremes (H2O)4-nLa(OH)nMAHx
°C (where the acid catalysed pathway is kinetically
unobservable). Therefore, species with more electron
can form and
a fraction of the La-MA complexes can
precipitate. ttMA recovery, and catalyst recycling are
withdrawing ability would be required.
described in more detail in the Supporting Information.
A large number of metal ions can bind to carboxylates and
hinder the undesired lactonization process.45 Notably, aqueous
lanthanum(III) exhibits large binding constants for
carboxylates, typically on the order of 103-105.45 A 20 mL
solution of 5.1 mM ccMA was prepared in D2O with an 89-fold
excess of Laaq3+. The 1H NMR is shown in Figure 6. The pD was
adjusted to a pH reading of 4.34 (pD = 4.45)46 with NaOH and
Production of 1,4-cyclohexanedioic acid
The further conversion of ttMA to CHDA was demonstrated
through Diels-Alder cycloaddition of ethylene to ttMA in γ-
valerolactone. The reaction resulted in the precipitation of
cyclohex-1-ene-1,4-dicarboxylic acid (>99 % yield). The product
was then esterified with methanol in the presence of H2SO4
due to solubility limitations for the subsequent hydrogenation
reaction. Interestingly, esterification prior to Diels-Alder
yielded cyclohex-2-ene-1,4-dimethyl ester in >94 % yield. The
hydrogenation was then performed in a three-phase plugged
flow reactor using Pt/C as a catalyst. The corresponding
saturated ester (CHDAMe2) was obtained with 92 % yield at 97
% conversion.
HNO3 in D2O. After 5.8 days at 90°C the conversion of ccMA
was 75 % and ttMA was observed in 41 % yield (55 %
selectivity); the solution was also composed of 14 % Mlac, 25%
Table 2. Isomerization Solvent Screening
Solventa
Main Product
Mlac
Acetone
Toluene
Mlac
Acetonitrile
THF
Mlac
Mlac
Conclusion
Ethyl Acetate
2-Propanol
Triethylamine
Methanol
DMSOb
Mlac
A key hindrance to biorenewable CHDA and TPA from MA is
the efficient isomerization of the biologically produced cis,cis-
isomer to Diels-Alder active trans,trans-MA. In aqueous
solutions ccMA readily isomerizes to ctMA which does not
isomerize to ttMA, but instead produces Mlac. The driving
forces for lactonisation are dependent upon pH. Below pH 2
the reaction is acid catalysed. Between pH 2 and 3 non-
innocent interactions with the solvent drive lactonisation.
Intramolecular interactions are responsible for lactonisation
between pH 3 and 6, and above pH 6 the isomers are
stabilized. Isomerization can be achieved by addressing the
Mlac
Degradation
Mlac
ttMA
Hexanol
Mlac
a 3 ± 1 mg ccMA was added to 5 mL solvent, capped, and placed in an oven at 75
°C for 2 weeks. MA was recovered by rotary evaporation and re-dissolved in
deuterium oxide for analysis by 1H NMR. b DMSO-d6 to eliminate the need for
evaporation of solvent.
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intramolecular interactions with aqueous lanthanum(III) salts. the solvent was reached. The temperature was then increased
Strategies related to solvent driven lactonisation utilizing to 200 °C. After the reaction proceeded for the desired time
DMSO were also successful in producing ttMA. While the exact (8-24 hrs), the reactor was cooled to room temperature and
role of the solvent is unknown, it is clear that many solvents depressurized. The liquid phase reaction products were then
are non-innocent and their role in formation/stabilization of collected, filtered through a cellulose filter dried, re-dissolved
the transition states is non-trivial. A more in-depth study of in DMSO-d6 and analysed by NMR.
MA reactions in DMSO would add significantly to our
Hydrogenation of CH2DAMe2 was carried out in a stainless
fundamental understanding of the reaction and to the steel packed bed reactor using 10 mg of 5 wt % Pt/C catalyst
development of economically viable industrial processes for diluted with 100 mg of glass beads (45-90 µm). The reactor
the production of bio-derived monomers from muconic acid.
was operated in an upflow configuration at the temperatures
of 250 °C. The temperature was maintained using
a
thermocouple and a PID controller. Reactions were conducted
at hydrogen pressures of 8 bars. The gas flow rate was
maintained at 20 ml/min using a Brooks SLA5850 flow
controller. The reactant was dissolved in dioxane to obtain a
concentration of 11.4 mg/ml. The liquid reactant feed was
introduced in the reactor at a rate of 0.4 ml/min using an HPLC
pump (Lab Alliance Series I). Product samples were collected
every 15 minutes. The samples were dried overnight to
evaporate the solvent. The dried samples were then dissolved
in 600 μL DMSO-d6 and 1,3,5-tribromobenzene was added as
an internal standard for analysis using 1H NMR.
Experimental
Cis,cis-muconic acid (ccMA), trans,trans-muconic acid (ttMA),
D2O (99.9 % D), lanthanum hydroxide (La(OH)3), acetic acid
(AA), sodium perchlorate (NaClO4), perchloric acid (HClO4),
trimethylamine, γ-valerolactone (GVL), and methanol (MeOH)
were purchased from Sigma-Aldrich. Sodium hydroxide
(NaOH), acetone, toluene, THF, ethyl acetate, 2-propanol,
dioxane, and hexanol were purchased from Fisher. Ethylene
99.5 % was purchased from Airgas. DMSO-d6 (99.96 % D) and
acetonitrile-d3 (99.96 % D) were purchased from Cambridge
Isotopes Laboratories. All chemicals were used as purchased.
Cis,trans-muconic acid (ctMA) was prepared by methods
previously described in the literature.15
Acknowledgements
A base solution containing ccMA and AA (internal standard) This material is based upon work supported in part by Iowa
was prepared in D2O; separate solutions of HClO4, NaOH, and State University and the National Science Foundation Grant
NaClO4 were prepared in D2O. Aliquots of each solution were Number EEC-0813570. We gratefully acknowledge Mr. Bradley
added to J. Young tubes, sealed, and placed in an oven. Schmidt of the Sadow group at Iowa State University for drying
Samples were removed from the oven, cooled to room the DMSO-d6, and the Iowa State University Chemical
temperature, and analysed by 1H NMR. Kinetic traces were Instrument Facility staff members.
constructed from MA signals relative to AA internal standard.
Isomerization of ccMA to ctMA at either 75.5 of 83.3 oC
1
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