Selective Production of Terminally Unsaturated Methyl Esters from Lactones Over Metal Oxide Catalysts

Article abstract of DOI:10.1007/s10562-018-2507-0

Metal oxide catalysts were studied for their selectivity for the production of a terminally unsaturated methyl ester, methyl 5-hexenoate (M5H), from a 6 carbon, 6-membered ring lactone, δ-hexalactone (DHL). A 15?wt% Cs/SiO₂ catalyst had a selectivity of 55% to M5H. This selectivity was the highest of the metal oxide catalysts studied, which were Cs/SiO₂, MgO, SrO, CeO₂, ZrO₂, Ta₂O₅, MgAl₂O₄, and a Mg–Zr mixed oxide. The Cs/SiO₂ catalyst was utilized for the ring-opening of γ-valerolactone (GVL), a 5 carbon, 5-membered ring lactone. The catalyst was 88% selective to the terminally unsaturated methyl ester, methyl 4-pentenoate (M4P). Weight hourly space velocity studies determined that the unsaturated ester distributions remained constant and no C=C double bond isomerization occurred. Liquid phase transesterification reactions with DHL and methanol and nuclear magnetic resonance spectroscopy confirmed that DHL undergoes ring-opening transesterification to produce an?ω-1 hydroxy methyl ester, methyl 5-hydroxyhexanoate (M5HH). Liquid phase transesterification reactions and thermochemistry calculations established that the equilibrium for GVL transesterification with methanol was favored towards the ring-closed lactone instead of the ring-opened hydroxy ester because of the decreased ring strain of GVL compared to DHL. The difference in terminally unsaturated methyl ester selectivity between GVL and DHL manifests from the difference in ring-strain energy. DHL passes through the M5HH intermediate as a result of greater ring strain, while the production of M4P from GVL most likely occurs through a direct, concerted mechanism. Graphical Abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s10562-018-2507-0

Catalysis Letters
https://doi.org/10.1007/s10562-018-2507-0
Selective Production of Terminally Unsaturated Methyl Esters
from Lactones Over Metal Oxide Catalysts
1
1
1
Zachary J. Brentzel · Madelyn R. Ball · James A. Dumesic
Received: 12 June 2018 / Accepted: 25 July 2018
©
Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Metal oxide catalysts were studied for their selectivity for the production of a terminally unsaturated methyl ester, methyl
5
-hexenoate (M5H), from a 6 carbon, 6-membered ring lactone, δ-hexalactone (DHL). A 15 wt% Cs/SiO catalyst had a
2
selectivity of 55% to M5H. This selectivity was the highest of the metal oxide catalysts studied, which were Cs/SiO , MgO,
2
SrO, CeO , ZrO , Ta O , MgAl O , and a Mg–Zr mixed oxide. The Cs/SiO catalyst was utilized for the ring-opening of
2
2
2
5
2
4
2
γ-valerolactone (GVL), a 5 carbon, 5-membered ring lactone. The catalyst was 88% selective to the terminally unsaturated
methyl ester, methyl 4-pentenoate (M4P). Weight hourly space velocity studies determined that the unsaturated ester dis-
tributions remained constant and no C=C double bond isomerization occurred. Liquid phase transesterification reactions
with DHL and methanol and nuclear magnetic resonance spectroscopy confirmed that DHL undergoes ring-opening trans-
esterification to produce an ω-1 hydroxy methyl ester, methyl 5-hydroxyhexanoate (M5HH). Liquid phase transesterification
reactions and thermochemistry calculations established that the equilibrium for GVL transesterification with methanol was
favored towards the ring-closed lactone instead of the ring-opened hydroxy ester because of the decreased ring strain of GVL
compared to DHL. The difference in terminally unsaturated methyl ester selectivity between GVL and DHL manifests from
the difference in ring-strain energy. DHL passes through the M5HH intermediate as a result of greater ring strain, while the
production of M4P from GVL most likely occurs through a direct, concerted mechanism.
Graphical Abstract
Extended author information available on the last page of the article
Vol.:(0
1
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3

Z. J. Brentzel et al.
Keywords Biorenewable chemicals · Heterogeneous catalysis · Metal oxides · Ring-opening · Terminally unsaturated
methyl esters
1
Introduction
commercially today. All three diols are used in the syn-
thesis of polyesters, plasticizers, polyurethanes, and resins
[19]. Synthesizing terminally unsaturated acids or esters
is a promising lactone upgrading route, since the resulting
double bond can be functionalized by a variety of reactions,
such as hydroformylation, hydroamination, hydrocyanation,
hydration, and hydroacylation [23].
Cyclic esters, or lactones, are a class of biorenewable mol-
ecules that can be derived from both lignocellulosic biomass
and secondary metabolites of microorganisms. An emerg-
ing trend in research is to couple biological and chemical
catalysis to produce high value commodity or specialty
chemicals [1–4]. Biology has evolved to produce secondary
metabolites with relevance to the chemical industry, such
as pyrones, carboxylic acids, and bifunctional molecules [1,
In the present work, we study the selectivity for the ring-
opening of δ-hexalactone (DHL) and GVL towards their
respective methyl unsaturated esters. Various heterogeneous
base catalysts were studied, including catalysts synthesized
from alkali acetate that have been previously demonstrated
to selectively produce terminally unsaturated esters [24].
The Cs/SiO2 catalyst was the most selective of the catalysts
studied for the production of terminally unsaturated esters.
Nuclear magnetic resonance (NMR) spectroscopy, density
functional theory (DFT), and probe alcohol dehydration
reactions were used to elucidate the differences in termi-
nally unsaturated ester selectivity between DHL and GVL.
5
, 6].
One such biologically derived platform pyrone is tri-
acetic acid lactone (TAL). TAL is a 2-pyrone synthesized
by the polyketide pathway [1, 7, 8]. TAL is promising as a
biologically-derived platform chemical for its many unique
functional groups. Selective catalytic upgrading of highly
oxygenated and functionalized molecules becomes easier
when there are fewer repeated moieties. Prior studies have
demonstrated the wide array of products that can be synthe-
sized from TAL [9]. An initial decarboxylation of TAL leads
to acetylacetone. The remainder of the products require at
least one C=C hydrogenation of the inner ring to synthesize
downstream products. These products include sorbic acid,
parasorbic acid, pentadiene, and hexalactones.
2
Experimental Details
2.1 Catalysts
γ-Valerolactone (GVL) is the most commonly synthesized
lactone from lignocellulosic biomass. GVL is synthesized
from cellulose-derived levulinic acid [10, 11]. GVL has
found applications as a platform molecule for both fuels and
chemicals [12]. GVL also has potential use as a green, polar
aprotic solvent [13, 14].
Commercial magnesium oxide (MgO) (Aldrich, 99.99%),
strontium oxide (SrO) (Aldrich, 99.9%), cerium(IV) oxide
(
(
(
CeO ) (Aldrich, ≥ 99%), tantalum(V) oxide (Ta O )
2
2
5
Aldrich, 99.99%), and magnesium aluminate (MgAl O )
2
4
Aldrich, spinel nanopowder) were used as purchased and
Lactones are a key starting point to synthesize down-
stream products, such as unsaturated acids, hydroxy acids, or
olefins [15–17]. Frequently, these lactones are required to be
ring-opened. Homogeneous or heterogeneous acid catalysts
will form the carbocation and yield internally unsaturated
carboxylic acids, such as sorbic acid or pentenoic acids [9].
Sorbic acid is used as a food grade preservative and has
annual production volumes of 65 kt/year [18]. Pentenoic
acids have more limited uses industrially but find uses in
synthetic cheeses.
in situ pretreated at 673 K in flowing He (Airgas, industrial
grade) for 30 min prior to reaction.
The 15% Cs/SiO catalyst was prepared by incipient wet-
2
ness impregnation. The appropriate mass of cesium acetate,
CH COOCs, (Sigma, ≥99.99%) was dissolved in deionized
3
water (Millipore Milli-Q grade, 18 MΩ) and added drop-
wise to silica gel SiO (Davisil Grade 646). The catalyst
2
was calcined under flowing air (Airgas, medical grade). The
temperature was held at 393 K (1.6 K/min) for 4 h and then
7
23 K (2.8 K/min) for 16 h.
The objective of our work is to elucidate the performance
of heterogeneous catalysts to selectively produce terminally
unsaturated acids or esters from biologically-derived lac-
tones. Both homo- and hetero- α,ω-functionalized mol-
ecules have found extensive use in industry. Some of the
largest volume α,ω-functionalized molecules synthesized
commercially are α,ω-diols [19, 20], α,ω-carboxylic acids
The zirconium dioxide (ZrO ) catalyst was synthesized
2
by precipitation, based on methods from Serrano Ruiz et al.
[
(
25] ZrO(NO ) (Aldrich) was precipitated with NH OH
3
2
4
Aldrich). NH OH was added to maintain a pH of 10. The
4
resulting slurry was stirred for 65 h. The filtered precipitates
were calcined in flowing air (Airgas, medical grade) for 4 h
at 723 K.
[
21], α,ω-amines [22]. Ethylene glycol, 1,4-butanediol, and
,6-hexanediol are the largest volume α,ω-diols produced
The MgO/ZrO catalyst was prepared by precipitation of
x
1
Mg(NO ) ·6H O and ZrOCl ·6H O with NaOH (Aldrich)
3
2
2
2
2
1
3

Selective Production of Terminally Unsaturated Methyl Esters from Lactones Over Metal Oxide…
[
26]. The molar ratio of Mg(NO ) ·6H O to ZrOCl ·6H O
samples were collected from the condensed effluent every
2–8 h. The vapor phase was sampled via online gas chro-
matography (Shimadzu GC2010 equipped with a flame ioni-
zation detector (FID) and a RT-Q-Bond column). Liquid
samples were analyzed by gas chromatography (Shimadzu
GC2010 equipped with a FID and a DB-5MS capillary
column).
3
2
2
2
2
was 10.9. NaOH was added to maintain a pH of 10. The
filtered precipitates were calcined in flowing air (Airgas,
medical grade) for 4 h at 873 K.
All catalysts were pre-treated in situ in flowing He (Air-
gas, industrial grade) at 673 K for 30 min prior to reaction.
2
.2 Carbon Dioxide Temperature Programmed
The catalysts were pretreated in flowing He (Airgas,
industrial grade) at 673 K for 1 h prior to the reaction. The
reactor was then cooled to a reaction temperature of 598 K.
The flowing He was then used as a sweep gas at the effluent
of the reactor. The liquid feeds, either 50 wt% GVL (Sigma,
≥ 99%) in methanol (Fisher Chemical, ≥ 99.9%), 50 wt%
DHL in methanol, neat 1-octanol (Sigma-Aldrich, ≥99%),
or neat 2-octanol (Sigma-Aldrich, ≥99%), were supplied
to the reactor via high performance liquid chromatography
(HPLC) pump (Lab Alliance Series 1).
Desorption (TPD)
1
30 mg of the 15% Cs/SiO catalyst was loaded into a frit-
2
ted quartz tube and then into a temperature controlled (Love
Controls) tube furnace. Vapor phase effluent was continu-
ously sampled by a mass spectrometer (Pfeiffer Vacuum,
Onmistar). The catalyst was first purged with He for 15 min
at room temperature (Airgas, UHP). The catalyst was
then pretreated in flowing He (Airgas, UHP) at 673 K for
3
0 min. The furnace was cooled and held at 298 K. CO
2
was adsorbed on the catalyst at 298 K from a 5% CO /N
2.5 Liquid Phase Transesterification Reactions
2
2
(
Airgas) flow for 30 min. Then, UHP He was passed over the
catalyst at 298 K for 1 h to remove weakly adsorbed CO .
The liquid phase transesterification reactions were per-
formed at room temperature in thick walled glass reactors
(Alltech, 10 mL) with magnetic stir bars. Feed solutions
of 1.5 g each of lactone and methanol (Fisher Chemical,
2
After stabilizing the mass spectrometer signal, the sample
was heated to 973 K (10 K/min). The reported base site
densities are calculated from the CO signal.
2
≥
99.9%) were loaded into the glass reactors. The feeds from
2
.3 Scanning Transmission Electron Microscopy
each reaction were collected and analyzed by gas chromatog-
raphy (Shimadzu GC2010 equipped with a FID and a DB-
(STEM)
5
MS capillary column). 0.01 g of concentrated sulfuric acid
A FEI Titan STEM with Cs probe aberration corrector oper-
ated at 200 kV with spatial resolution< 0.1 nm was used
for STEM studies. Images were collected using high-angle
annular dark-field (HAADF) mode, with HAADF detector
angle ranging from 54 to 270 mrad, probe convergence angle
of 24.5 mrad, and probe current of approximately 25 pA.
Energy dispersive X-ray spectroscopy (EDS) data were
collected using the same microscope with an EDAX SiLi
Detector. Catalyst samples were suspended in ethanol and
then dropped on a holey carbon Cu TEM grid.
(Sigma-Aldrich, 95–98%) was then added to each reactor.
The reactors were stirred at room temperature for 72 h and
sampled every 24 h. The reactor samples were neutralized
and analyzed by gas chromatography.
2.6 Nuclear Magnetic Resonance (NMR)
Spectroscopy
Two samples were analyzed by NMR spectroscopy. The first
sample was a 50 wt% DHL (Alfa Aesar, 98%) in deuterated
dimethyl sulfoxide (DMSO-d6) (Aldrich, ≥ 99.9% atomic
percentage deuterium, contains 1% (v/v) TMS) solution.
The second sample was the liquid phase transesterification
product of 50 wt% DHL in methanol with 25 mM of sulfu-
ric acid. The reaction product mixture was combined with
50 wt% DMSO-d6 before NMR analysis. One-half a gram
of each solution was added to an NMR tube (Wilmad, 5 mm
borosilicate glass).
2.4 Vapor Phase Ring‑Opening Reactions
The vapor phase ring-opening and dehydration studies were
performed in a fixed bed catalytic reactor in an up-flow con-
figuration at 598 K and 3.5 atm. The catalyst to be studied
was loaded into a 1/4” OD stainless steel tube and secured in
place by alternating layers of quartz wool (Grace) and granu-
lar silicon dioxide (Sigma, 99.9%, 4–20 mesh). The silicon
dioxide was used to decrease void volume and increase heat
transfer. The quartz wool layers served as a buffer between
the catalyst and silicon dioxide layers. The tube was secured
in a furnace comprised of aluminum blocks, heating tape
NMR experiments were performed on a Bruker Avance-
III 500 MHz spectrometer with a DCH cryoprobe. All spec-
2
tra were collect at 297 K. The H signal from DMSO-d6
was used as the field-frequency lock. The magnetic field
2
1
shimming was performed on the H solvent signals. H and
1
3
(
Briskheat, 135 W), and insulation. The vapor phase reactor
C chemical shifts were referenced against the tetramethyl-
1
effluent was passed through an ice bath condenser. Liquid
silane (TMS) peak in the DMSO-d6 solvent. H experiments
1
3

Z. J. Brentzel et al.
were performed with a Bruker standard 1D pulse sequence,
zg30’. The inter-scan relaxation delay, sweep width, acqui-
scan had the following parameters: 12 ppm sweep width in
1
‘
F2 ( H), centered at 4.7 ppm, acquiring 4096 data points,
1
3
sition time, and number of scans were 2 s, 20 ppm centered
240 ppm sweep width in F1 ( C), centered at 110 ppm,
acquiring 256 increments, 4 scans per increment, an 8 Hz
long range coupling constant, and a 2 s relaxation delay.
1
3
at 10 ppm, 3.3 s, and 8 scans, respectively. C spectra were
1
collected with a H decoupled pulse sequence, ‘zgpg30’.
The inter-scan relaxation delay, sweep width, acquisition
time, and number of scans were 2 s, 284 ppm centered at
2.7 Density Functional Theory (DFT) Calculations
1
3
1
10 ppm, 2 s, and 32 scans, respectively. The C distortion-
less enhancement of polarization transfer with a 135° angle
Gaussian 09 software was used for DFT calculations to esti-
mate the gas phase thermochemistry for the ring-opening
transesterification of DHL and GVL with methanol. Geome-
try optimizations and frequency calculations were performed
using B3LYP/6-311+G(2d,p).
for the φ pulse (DEPT-135) spectrum was collected with a
3
Bruker standard pulse sequence, ‘deptsp135’. The inter-scan
relaxation delay, sweep width, acquisition time, and number
of scans were 2 s, 284 ppm centered at 110 ppm, 1 s, and
1
1
3
2 scans, respectively. 2D H– H homonuclear correlation
spectroscopy (COSY) spectra were collected with a Bruker
standard pulse sequence, ‘cosygp45’. The scan had the fol-
3 Results and Discussion
1
lowing parameters: 16 ppm sweep width in F2 ( H), centered
at 4.5 ppm, acquiring 2048 data points, 16 ppm sweep width
The proposed reaction networks for the production of ter-
minally unsaturated methyl esters from DHL and GVL are
shown in Fig. 1. Eight catalysts were studied for their selec-
tivity to the production of methyl 5-hexenoate (M5H) from
DHL, shown in Table 1. When using a commonly studied
heterogeneous base, MgO, the reaction had a mass balance
of only 70%, with 50% of the remaining carbon converted
to unknown products. The reactor effluent contained solid
particles, indicative of polymer formation. Additionally,
the distribution of methyl 4-hexenoate (M4H) to M5H
unsaturated esters was nearly 2:1. There was no selec-
tivity to either of the two other most common products,
1
in F1 ( H), centered at 4.5 ppm, acquiring 256 increments, 2
1
13
scans per increment, and a 2 s relaxation delay. 2D H– C
heteronuclear single quantum coherence (HSQC) spec-
tra were collected with a Bruker standard pulse sequence,
‘
hsqcetgp’. The scan had the following parameters: 12 ppm
1
sweep width in F2 ( H), centered at 4.7 ppm, acquiring 2048
1
3
data points, 180 ppm sweep width in F1 ( C), centered at
8
5 ppm, acquiring 256 increments, 2 scans per increment,
1
13
and a 2 s relaxation delay. 2D H– C heteronuclear mul-
tiple-bond correlation spectroscopy (HMBC) spectra were
collected with a standard pulse sequence, ‘hmbcetgp’. The
(
A)
(
B)
Fig. 1 Proposed reaction pathways for the production of a methyl hexenoates from of DHL and methanol and b methyl pentenoates from GVL
and methanol
1
3

Selective Production of Terminally Unsaturated Methyl Esters from Lactones Over Metal Oxide…
Table 1 Selectivity for the vapor phase lactone ring-opening of DHL with a methanol co-feed for heterogeneous catalysts
Catalyst
Conversion Methyl 5-hexenoate
Methyl 4-hexenoate
Selectivity to methyl 5-hydrox-
Selectivity to
(
%) (M5H) selectivity (mol%) (M4H) selectivity (mol%) yhexanoate (M5HH) (mol%)
cyclohexenone
(
mol%)
MgO
SrO
CeO2
MgZr
ZrO2
93
10
60
11
32
18
11
15
77
12
18
3
24
2
22
1
6
45
55
0
32
3
26
1
7
1
0
94
54
94
23
94
64
35
15
100
0
0
0
2
22
0
0
0
0
0
MgAl O4
2
Ta O
3
2
5
1
1
5% Cs/SiO2
5% Cs/SiO2
19
30
0
a
SiO2
The reactions were carried out at 598 K, 3.5 bar, and 50 wt% DHL in methanol feed
a
The second entry for 15% Cs/SiO provides results from a reaction carried out at longer space time
2
methyl 5-hydroxyhexanoate (M5HH) and cyclohexenone.
Reactions with the remainder of the catalysts resulted in
selectivities of at least 23% to M5HH. Zr-containing cata-
lysts, both MgZr and ZrO , had selectivities between 2
2
and 22% to cyclohexenone. No other catalysts produced
cyclohexenone. We hypothesize that the production of
cyclohexenone is a function of the amphoteric nature of the
Zr catalysts [27]. MgZr and ZrO also had the largest ratio
2
of M5H to M4H. Cs/SiO had 64% selectivity to the unsatu-
2
rated esters and 35% to M5HH at 15% conversion. Cs/SiO
2
had 45% selectivity to M5H. Ta O had 62% distribution to
2
5
M5H, but mainly produced M5HH, while SrO, CeO , and
2
MgAl O were more selective to the internal unsaturated
2
4
ester, M4H, than the terminal unsaturated ester, M5H.
The Cs-containing catalyst was used for further study
of ring-opening of DHL and GVL since it had the high-
est selectivity and yield to M5H. The maximum yield to
the terminal unsaturated ester was studied for each lactone.
There was 88% selectivity to methyl 4-pentenoate (M4P)
and 6% selectivity to methyl 3-pentenoate (M3P) at 63%
conversion of GVL, which is the equilibrium conversion.
However, there was only 55% selectivity to M5H and 30%
selectivity to M4H at 77% conversion from DHL, which is
the equilibrium conversion.
Fig. 2 Scanning transmission micrograph of 15% Cs/SiO catalyst
2
showing 10–85 nm cesium particles
CO began desorbing at 30 °C and had completely desorbed
2
The synthesis of Cs/SiO by wetness impregnation of sil-
by 200 °C, which is indicative of a weak base. A weaker
base is preferred for a selective lactone ring opening because
stronger bases, such as MgO, had poorer selectivity to the
terminally unsaturated methyl esters.
2
ica with cesium acetate and subsequent calcination results in
cesium carbonate and cesium oxide nanoparticles supported
on the silica support [24]. Cs nanoparticles can be seen in
the scanning transmission electron micrographs in Fig. 2.
EDS was used to confirm that these were Cs-containing par-
ticles. The cesium nanoparticles had particle sizes ranging
from 10 to 85 nm. Cesium oxide is a heterogeneous base,
Weight hourly space velocity studies were performed to
determine if the differences in selectivities to the terminal
unsaturated esters for the C5 and C6 lactones were a func-
tion of C=C double bond isomerization, as shown in Fig. 3.
Neither the hexenoate nor pentenoate esters isomerized with
increasing space time. The distribution to M4P was 94%
and CO TPD was used to quantify the base site density.
2
The catalyst had a base site density of 7.4 µmol/g, and the
1
3

Z. J. Brentzel et al.
Fig. 3 The distribution of terminal unsaturated esters to all unsatu-
lactone in methanol feed. The data correspond to samples taken at
rated ester production for a GVL and b DHL over a 15 wt% Cs/SiO
steady state. Units of space time are h g /g
2
cat lactone
catalyst. The reactions were carried out at 598 K, 3.5 bar, and 50 wt%
from 20% conversion up to 60% conversion. The distribu-
tion to M5H remained at 65% from 8% conversion to 77%
conversion.
Table 2 Conversion to the respective ω-1 hydroxy ester for two
5
-membered ring and two 6-membered ring lactones
Molecule
Equilibrium conversion to hydroxy
ester (%)
Ring-opening of GVL and DHL occur through separate
mechanisms over the Cs/SiO catalyst since C=C double
2
298 K, liquid phase 598 K,
3.5 bar, vapor
bond isomerization does not occur and there is a 30% dif-
ference in the distribution to the terminal unsaturated esters.
A reactor absent of a catalyst and only packed with inert,
high purity fused silicon dioxide granules was studied to
determine if there were any differences in conversion or
selectivity for the C5 and C6 lactones. This blank reaction
demonstrated that there was 12% conversion to the transes-
terification product, methyl 5-hydroxyhexanoate (M5HH),
for the DHL feed. The same reaction performed with GVL
only yielded <1% to its transesterification product, methyl
phase
γ-Valerolactone (GVL)
γ-Hexalactone (GHL)
δ-Nonalactone (DNL)
δ-Hexalactone (DHL)
21
12
87
92
<1
Not run
Not run
12
The vapor phase reactions were carried out at 598 K, 3.5 bar, and
5
0 wt% DHL in methanol feed with only SiO granules in the reactor.
2
The liquid phase reactions were conducted at 298 K for 72 h with 5 g
of 50 wt% lactone in MeOH with 1 drop of 70 wt% HCl
4
-hydroxypentanoate (M4HP).
Further studies were conducted in the liquid phase to
determine the extent of transesterification between the
lactones and their ring-opened ω-1 hydroxy methyl esters.
The 50 wt% lactone feeds in methanol were prepared and
allowed to equilibrate at room temperature for 1 week. Anal-
ysis of each mixture after that week showed that the GVL
and methanol mixture had not undergone conversion, while
the DHL and methanol feed had reached 50% yield to the
hydroxy ester. A subsequent experiment was conducted to
study the equilibrium transesterification conversion at room
temperature by adding a small amount of acid. Each mixture
was acidified to 25 mM with 95% H SO , stirred at room
converted by 92% to M5HH, while GVL was converted by
only 21% to M4HP.
To study the effects of lactone ring-size further, we per-
formed the same experiment with γ-hexalactone (GHL) and
δ-nonalactone (DNL). GHL is a 5-membered lactone ring
with an ethyl group substituent, and DNL is a 6-membered
lactone ring with a butyl functional group, shown in Fig. 4.
Lactone ring-size is the determining factor in the equilib-
rium conversion to the respective ω-1 hydroxy esters. The
6-carbon GHL has 12% equilibrium conversion to its trans-
esterified product, methyl 4-hydroxyhexanoate (M4HH).
That value is closest to the 5-membered lactone, GVL, and
not the 6-membered ring, DHL. The 9-carbon, 6-membered
ring DNL has 87% equilibrium conversion to its hydroxy
2
4
temperature for 72 h, and sampled every 24 h. The mixtures
reached equilibrium conversion by 24 h. The yields to the
respective hydroxy esters are shown in Table 2. DHL was
1
3

Selective Production of Terminally Unsaturated Methyl Esters from Lactones Over Metal Oxide…
(
A)
(B)
(D)
(
C)
Fig. 4 Transesterification of a GVL to M4HP, b GHL to M4HH, c DHL to M5HH, and d DNL to M5HN
ester, methyl 5-hydroxynonanoate (M5HN). This value is
comparable to the 6-membered ring, DHL, which has 92%
conversion. Liquid phase transesterification of lactones with
methanol is predominantly a function of ring size and not
carbon number. Only DHL and GVL were studied for their
conversion to ω-1 hydroxy esters under vapor phase reac-
tion conditions over high purity silicon dioxide granuales.
Although, the conversion in the vapor phase is not neces-
sarily equilibrium conversion, the same trend was observed.
The 6-membered ring DHL underwent 12% conversion
to the M5HH, while GVL underwent < 1% conversion to
M4HP.
Table 3 Thermochemistry values for the transesterification of lac-
tones and methanol to their respective ω-1 hydroxy methyl esters at
98 K
2
Reactant
ΔH (kJ/mol) ΔS (kJ/mol/K) ΔG (kJ/mol)
γ-Valerolactone (GVL) −19.1
γ-Hexalactone (GHL) −19.5
δ-Nonalactone (DNL) −36.7
δ-Hexalactone (DHL) −35.1
−0.13
−0.13
−0.13
−0.12
19.4
18.8
1.8
2.1
Energies were estimated using B3LYP/6-311+G(2d,p) with Gaussian
9 DFT (DFT) software
0
The hypothesized reason for such large discrepancies
between equilibrium conversion to the respective transesteri-
fied hydroxy esters between the 5- and 6-membered ring lac-
tones is the ring strain. Calorimetry experiments have deter-
mined that 5-membered ring, GVL, has 30.5 kJ/mol of ring
strain, while a 6-membered lactone ring, δ-valerolactone
performed for both 50 wt% DHL in DMSO-d6 and the 50:50
w/w DHL:MeOH solution with 25 mM of sulfuric acid
1
13
diluted in 50 wt% DMSO-d6. The H decoupled C NMR
spectra for both DHL and M5HH are shown in Fig. 5. The
1
3
peaks were assigned by comparing the C DEPT-135, 2D
1
1
1
13
1
13
H– H COSY, 2D H– C HSQC, and 2D H– C HMBC
1
3
(
DVL) has 39.7 kJ/mol [28]. Stedjan et al. have performed
spectra. The C DEPT-135 spectrum for M5HH, shown in
DFT calculations and found that the difference in ring strain
energy between 5- and 6-membered lactone rings was 9.6 kJ/
mol, similar to what was determined experimentally [29].
Additional thermochemistry calculations were performed
using Gaussian 09 DFT software to predict the gas phase
energies for all of the reactants and products. The Gibbs free
energy change at 298 K for the transesterification of the two
Fig. 6, confirms the proper orientation of –CH peaks as
2
negative, while the –CH and –CH peaks are positive. The
3
key evidence to distinguish between the ring-closed lactone
and the ring-opened hydroxy ester is ascertained with 2D
1
13
H– C HMBC. This technique is used to detect proton-car-
bon correlation over a 2–3 bond range. HMBC has been suc-
cessfully applied to confirm lactone structures through the
cyclic heteroatom previously in literature [30–33]. HMBC
results for DHL demonstrate that the ester carbon, denoted
6, is correlated with protons on carbons 1, 4, and 5, as shown
in Fig. 7a. There was a smaller peak corresponding to the
correlation with protons on carbon 2. The protons on carbon
3 were not coupled with carbon 6 with the coupling constant
of 8 Hz. The HMBC spectrum of M5HH proved that carbon
6 was only correlated with protons on carbons 4, 5, and 7,
as shown in Fig. 7b. The lack of correlation to protons on
carbons 1, 2, or 3 confirm the presence of a ring-opened
species.
5
-membered ring lactones, GVL and GHL, was 19 kJ/mol,
while the free energy change for the two 6-membered ring
lactones, DHL and DNL, was 2 kJ/mol. This trend corre-
sponds with the trend observed for the liquid phase equilib-
rium conversion of the lactones to their respective hydroxy
esters (Table 3).
NMR spectroscopy was used to probe the structure of
the ring-opened, transesterified product, M5HH. Carbon and
hydrogen peaks for DHL were also identified and confirmed.
1
13
13
1
1
Standard H, standard C, C DEPT-135, 2D H– H COSY,
1
13
1
13
2
D H– C HSQC, and 2D H– C HMBC scans were
1
3

Z. J. Brentzel et al.
(A)
(B)
Fig. 5 H decoupled 13C NMR spectra and peak identification of a 50 wt% DHL in DMSO-d8 and b reaction product from 50:50 (w/w)
1
DHL:MeOH with 25 mM concentrated sulfuric acid in 50 wt% in DMSO-d8
production of cis-2-octene. Therefore, there was negligible
C=C double bond isomerization for the linear alpha olefin.
Dehydration of 2-octanol can produce either 1- or 2-octenes
as primary products. Since we have demonstrated that there
is no C=C double bond isomerization, the selectivity to both
of these products results from the primary reaction of dehy-
dration. The selectivities for the dehydration of 2-octanol to
1
1
-octene, trans-2-octene, and cis-2-octene were 75, 10, and
5%, respectively. These distributions correlate well with
those obtained from the production of methyl hexenoates
from DHL. At equilibrium conversion of DHL, the distribu-
tion to the terminal unsaturated ester is 65%. The selectivi-
ties and lack of C=C double bond isomerization achieved
in the probe alcohol dehydration studies provide further evi-
dence that the 6-membered lactone ring, DHL, undergoes
a ring opening transesterification followed by dehydration,
as shown in Fig. 1. The differences in terminal unsaturated
ester selectivity, unfavorable transesterification thermody-
namics, and steric hindrance of methoxide addition to GVL
suggest that the 5-membered lactone ring undergoes a direct,
concerted ring-opening mechanism. This behavior allows for
higher selectivity to the terminal unsaturated bond.
13
Fig. 6 C DEPT-135 NMR spectrum and peak identification of the
reaction product from 50:50 (w/w) DHL:MeOH with 0.01 g concen-
trated sulfuric acid in 50 wt% in DMSO-d8. –CH peaks are negative.
2
–
CH and –CH peaks are positive
3
Since DHL undergoes homogenous transesterification to
M5HH under reaction conditions, we studied the selectivity
of alcohol dehydration to mimic the functionality of the ω-1
hydroxyl moiety of M5HH. 1- and 2-Octanol were chosen
as the probe alcohol molecules. Table 4 provides the results
from the alcohol dehydration studies. The dehydration of
4 Conclusions
1
-octanol was performed to verify the negligible C=C dou-
ble bond isomerization on the resulting alkene that had pre-
viously been observed for the unsaturated esters. 1-Octene
is the only primary product, and therefore, the formation
of 2-octene occurs as a secondary reaction through dou-
We have demonstrated that Cs/SiO catalysts display
2
> 55% selectivity to M5H from DHL and 88% selectivity
to M4P from GVL. The difference in selectivity manifests
from the larger degree of ring strain in the C6 lactone
compared to the C5 lactone. NMR experiments and liquid
phase transesterification reactions have determined that
the uncatalyzed product observed from the vapor phase
ble bond isomerization. At 8% conversion over Cs/SiO ,
2
1
-octanol dehydration was 99% selective to 1-octene. The
selectivity to trans-2-octene was only 1%, and there was no
1
3

Selective Production of Terminally Unsaturated Methyl Esters from Lactones Over Metal Oxide…
(
A)
(B)
Fig. 7 Heteronuclear multiple-bond correlation spectroscopy (HMBC) NMR spectra for the ester carbon, number 6, for a 50 wt% DHL in
DMSO-d8 and b reaction product from 50:50 (w/w) DHL:MeOH with 25 mM concentrated sulfuric acid in 50 wt% in DMSO-d8
Table 4 Conversion and selectivity of 1- and 2-octanol over Cs/SiO2
Feed Conversion Octene distribution (%)
References
1
.
Nikolau BJ, Perera MADN, Brachova L, Shanks B (2008) Plant
J 54:536–545
(%)
1
Trans-2-
Cis-2-
2
3
.
.
Shanks BH (2007) ACS Chem Biol 2:533–535
Schwartz TJ, O’Neill BJ, Shanks BH, Dumesic JA (2014) ACS
Catal 4:2060–2069
1
2
-Octanol
-Octanol
8
5
99
75
1
10
0
15
4
5
.
.
Schwartz TJ, Shanks BH, Dumesic JA (2016) Curr Opin Bio-
technol 38:54–62
The reactions were carried out at 598 K, 3.5 bar, and neat octanol
Bowen CH, Bonin J, Kogler A, Barba-Ostria C, Zhang F (2016)
ACS Synth Biol 5:200–206
reaction of methanol with DHL is the ring-opened, trans-
esterification product, M5HH. DFT calculations and liq-
uid phase transesterification reactions show that the equi-
librium distribution for the transesterified ω-1 hydroxy
methyl ester is significantly greater for 6-membered lac-
tone rings compared with 5-membered rings. Compara-
ble molar ratios of terminal to internal unsaturated C=C
bonds from dehydrations of a probe secondary alcohol,
6. Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011)
Nature 476:355–359
7
8
.
.
Cardenas J, Da Silva NA (2014) Metab Eng 25:194–203
Jez JM, Bowman ME, Noel JP (2002) Proc Natl Acad Sci USA
9
9:5319–5324
9. Chia M, Schwartz TJ, Shanks BH, Dumesic JA (2012) Green
Chem 14:1850
1
0. Alonso DM, Bond JQ, Dumesic JA (2010) Green Chem 12:1493
1. Wettstein SG, Alonso DM, Chong Y, Dumesic JA (2012) Energy
Environ Sci 5:8199
1
2
-octanol, suggests that the mechanism for production of
12. Horváth IT, Mehdi H, Fábos V, Boda L, Mika LT (2008) Green
Chem 10:238–242
M5H passes through the M5HH intermediate, while neg-
ligible conversion of GVL to M4HP indicates that GVL
undergoes a direct, concerted mechanism to M4P.
1
3. Mellmer MA, Martin Alonso D, Luterbacher JS, Gallo JMR,
Dumesic JA (2014) Green Chem 16:4659–4662
1
4. Mellmer MA, Sener C, Gallo JMR, Luterbacher JS, Alonso DM,
Dumesic J (2014) Angew Chem Int Ed Engl 53:11872–11875
Acknowledgements This material is based upon work supported by the
National Science Foundation Engineering Research Center for Biore-
newable Chemicals (CBiRC), under Award Number EEC-0813570.
The authors would like to thank the Magnetic Resonance Facility in
the Chemistry Department of the University of Wisconsin-Madison
for use of the Bruker Avance III 500 gifted by Paul J. Bender. The use
of facilities supported by the Wisconsin Materials Research Science
and Engineering Center is also acknowledged (DMR-1121288). We
thank Leo Manzer and Thomas Schwartz for helpful discussions about
lactone ring-opening. We thank Heike Hofstetter for discussions about
NMR analyses. Any opinions, findings, and conclusions or recommen-
dations expressed in this material are those of the authors and do not
necessarily reflect the views of the National Science Foundation.
15. Bond JQ, Wang D, Alonso DM, Dumesic JA (2011) J Catal
281:290–299
16. Bond JQ, Alonso DM, West RM, Dumesic JA (2010) Langmuir
26:16291–16298
17. Wang D, Hakim SH, Alonso DM, Dumesic JA (2013) Chem
Commun (Cambridge) 49:7040–7042
18. Dorko CL, Ford GT, Baggett MS, Behling AR, Carmen HE
(2014) Kirk-Othmer encyclopedia of chemical technology.
Wiley, Hoboken, pp 1–19
19. Werle P, Morawietz M, Lundmark S, Sörensen K, Karvinen E,
Lehtonen J (2008) Ullmann’s encyclopedia of industrial chem-
istry. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
3

Z. J. Brentzel et al.
2
0. Market sand Markets (2014) 1,6-Hexanediol market by applica-
tion (polyurethanes, coatings, acrylates, adhesives, unsaturated
polyester resins, plasticizers, and others) and by geography (NA,
Europe, Asia-Pacific, & ROW) - Trends and Forecasts to 2019,
26. Aramendía MA, Boráu V, Jiménez C, Marinas A, Marinas JM,
Navío JA, Ruiz JR, Urbano FJ (2004) Colloids Surf A 234:17–25
27. Ono Y, Hattori H (2011) Solid base catalysis, vol 101. Springer,
Berlin
2
014
28. Brown JM, Conn AD, Pilcher G, Leito MLP, Meng-Yan Y (1989)
J Chem Soc Chem Commun. https://doi.org/10.1039/C398900018
17
2
2
2
1. Oppenheim JP, Dickerson GL (2003) Kirk-Othmer encyclopedia
of chemical technology. Wiley, Hoboken
2. Sridhar S, Carter RG (2001) Kirk-Othmer encyclopedia of chemi-
cal technology. Wiley, Hoboken
29. Stedjan MK, Augspurger JD (2015) J Phys Org Chem 28:298–303
30. Boonphong S, Kittakoop P, Isaka M, Pittayakhajonwut D, Tan-
ticharoen M, Thebtaranonth Y (2001) J Nat Prod 64:965–967
31. Li X, Sattler I, Lin W (2007) J Antibiot (Tokyo) 60:191–195
32. Barrow CJ (1997) J Nat Prod 60:1023–1025
3. Beller M, Seayad J, Tillack A, Jiao H (2004) Angew Chem Int Ed
Engl 43:3368–3398
2
2
4. Manzer L US6835849B2, 2004, 1.
5. Serrano-Ruiz JC, Luettich J, Sepúlveda-Escribano A, Rodríguez-
Reinoso F (2006) J Catal 241:45–55
33. Colmenares AJ, Durán-Patrón RM, Hernández-Galán R, Collado
IG (2002) J Nat Prod 65:1724–1726
Affiliations
1
1
1
Zachary J. Brentzel · Madelyn R. Ball · James A. Dumesic
1
*
James A. Dumesic
jdumesic@wisc.edu
Department of Chemical and Biological Engineering,
University of Wisconsin-Madison, 1415 Engineering Drive,
Madison, WI, USA
1
3