Zemplén transesterification: A name reaction that has misled us for 90 years

Article abstract of DOI:10.1039/c4gc02006e

We demonstrated that using NaOH and NaOMe in methanol for deacylation are identical, indicating that the Zemplén condition has been misleading us for almost 90 years. The traditional base-catalyzed mechanism cannot be used to explain our results. We propose that H-bond complexes play key roles in the base-catalyzed process, explaining why deacylation in methanol can be catalyzed by hydroxide.

Full text of DOI:10.1039/c4gc02006e

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DOI: 10.1039/C4GC02006E
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Zemplén Transesterification: A Name Reaction Having
Been Misleading Us for 90 Years
Cite this: DOI: 10.1039/x0xx00000x
a
b
b
a
a
a,
Bo Ren, Meiyan Wang, Jingyao Liu, Jiantao Ge, Xiaoling Zhang and Hai Dong *
Received 00th January 2014,
Accepted 00th January 2014
DOI: 10.1039/x0xx00000x
www.rsc.org/greenchem
We demonstrated that using NaOH and NaOMe in methanol In this study, we proved that Zemplén condition had been
for deacylation are identical, indicating that Zemplén misleading us for almost 90 years. We found that deacylation using a
condition has been misleading us for almost 90 years. The hydroxyl anion base in methanol does not in fact require a
traditional base-catalyzed mechanism cannot be used to stoichiometric amount of base for each ester functional group. The
explain our results. We proposed that H-bond complexes play results of our experiments indicate that the use of NaOH in methanol
key roles in the base-catalyzed process, explaining why is identical to that of NaOMe in methanol for deacylation. The
deacylation in methanol can be catalyzed by hydroxide.
development of Zemplén condition was based on the tranditional
base-catalyzed mechanim which cannot be used to explain our
Acyl groups are widely used as protecting groups in organic results (Figure 1a). Therefore, deacylation can be performed with a
[
1]
synthesis strategies, especially in carbohydrate chemistry. With the catalytic amount of hydroxyl anion resin and the resin can be
addition of acylation reagents under mild conditions, the hydroxyl repeatedly reused in the same process after simply filtered. These
groups of substrates readily form esters as intermediate products, and results cannot be explained by traditional base-catalyzed mechanism.
the esters are easily removed under Zemplén conditions when We proposed that H-bond complex play key roles in this base-
1-2
required. For almost 90 years, it has been believed that the regular catalyzed process (Figure 1b), supported by theoretical studies. An
hydrolysis of an ester using a base such as potassium hydroxide inverse kinetic isotope effect (KIE) may give direct evidences to
(KOH) or sodium hydroxide (NaOH) requires a stoichiometric support the H-bond involved principle. Therefore, the tranditional
amount of base for each ester functional group, and generates a large base-catalyzed principle in textbook might be discarded.
amount of potassium or sodium acetate, whereas Zemplén
deacylation uses only a catalytic amount of sodium methoxide
2
(
NaOMe). Today, Zemplén deacylation, performed with a catalytic
amount of sodium methoxide in methanol, is a standard tool in
1
laboratories and industry settings. Its inherent disadvantage is the
retention in solution of sodium ions. As the sodium ions can be
+
removed using H -exchanged resin, industrial deacylation
+
techniques normally involve ion-exchanged columns. The H -
exchanged resin can be regenerated with acid after ion exchange.
The ion exchange procedure would be omitted from deacylation in
laboratories, and especially in industry settings, supposed that the
reaction were catalyzed by methoxyl anion resin. At first appearance,
it seems impossible due to the difficulty of acquiring methoxyl anion
resin. In 1981, Goodman’s group found that hydroxyl anion
exchanged resin could be used for the catalytic deacylation of sugars
Figure 1. a) Traditional mechanism of deacylation catalyzed by hydroxyl anion. b)
Our proposed mechanism of deacylation catalyzed by H‐bond complex.
3
We were surprised to find that the penta-acetyl glucosides were
completely deacetylated by 0.1 equiv. of NaOH in methanol. Indeed,
only 0.02 equiv. of NaOH was used for each ester functional group
of the glucoside. At first, this result seemed impossible due to the
preconception that deacylation with NaOH in methanol requires a
in methanol. They believed that the deacylation be catalyzed by
methoxyl anion and the methoxyl anion be generated by a series of
ion exchanges with the hydroxyl anion at the resin surface. Despite
4
its reported efficiency, this method has unfortunately not been
extensively adopted, likely because of the unconvincing explanation.
This journal is © The Royal Society of Chemistry 2014
Green Chemistry, 2014, 00, 1‐3 | 1

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COMMUNICATION
–
stoichiometric amount of base for each ester functional group, and Table 2. Deacylation catalyzed by NaOMe, NaOH or OH-resin.
generates a large amount of sodium acetate. To clarify the result,
e
Entry
Substrate
Product
VYiewieAldrticle Online
additional experiments were conducted to compare the use of NaOH
with that of NaOMe: 0.1, 0.02 and 0.01 equiv. of each of the two
bases was used to deacetylate glucoside 1 (entries 1 and 2 in Table
DOI: 10.1039/C4GC02006E
a,b
1
Quant
1
). The free glucoses 2 were obtained in quantitative yields in 0.5 h.
and 4 h. with the use of 0.1 and 0.02 equiv., respectively, of either
NaOH or NaOMe. When the amount of either base was decreased by
a,b
2
Quant
Quant
0.01 equiv., the deacetylation of glycoside 1 remained incomplete
until 24 hours. These results indicate that the use of NaOH in
methanol is identical to the use of NaOMe in methanol for the
deacylation of glucoside 1. In the following experiments, various
a,b
3
bases including KOH, sodium sulfide (Na S), potassium sulfide
2
(
K S), sodium carbonate (Na CO ), potassium carbonate (K CO ),
2 2 3 2 3
calcium oxide (CaO) and magnesium oxide (MgO), were used as
catalysts (entries 3-9 in Table 1). The deacetylation of 1 was
completed in 0.5 h. with 0.1 equiv. of KOH; in 1 h. with 0.1 equiv.
of Na S and K S; in 4 h. with 0.1 equiv. of Na CO and K CO ; and
in 8 h. with 0.2 equiv. of CaO. With 0.2 equiv. of MgO, the
deacetylation remained incomplete until 24 hours. These results
indicate that it is incorrect to assume that deacetylation can only be
catalyzed by the methoxyl anion in methanol. Dry methanol has
traditionally been used as the solvent on the grounds that any water
in the methanol will consume the NaOMe, thereby preventing
deacetylation. However, our experiments showed that water has little
effect on the deacetylation (entries 10 and 11 in Table 1). With 0.1
equiv. of NaOH or NaOMe, the deacetylation of 1 was completed in
a,b
4
Quant
Quant
2
2
2
3
2
3
a,b
5
a,b
6
Quant
Quant
Quant
a
7
0
.5 h. and 1 h. when the methanol contained 1% and 10% of water,
respectively. The deacetylation achieved around 60% completion
observed from TLC plate) even when the methanol contained 50%
(
a
of water.
8
a
Table 1. Deacylation of penta-acetyl glucoside 1 catalyzed by various bases.
c
9
Quant
Quant
d
1
0
b
Entry Base
Amount (eq.) Time/h
Yield
0
.1
0.02
.01
.1
0.02
.01
0.5
4
24
0.5
4
24
0.5
1
Quant.
Quant.
-
[a]
Reagents and conditions: substrates (100 mg), NaOMe or NaOH (0.1 eq.),
1
2
NaOMe
[b]
MeOH (1 mL), rt.; substrates (100 mg), hydroxyl anion resin (85 mg/ 0.1
c
0
0
[c]
eq.), MeOH (1 mL), rt.; substrates (100 mg), NaOMe or NaOH (1.1 eq.),
Quant.
Quant.
[d]
MeOH (1 mL), rt.; substrates (100 mg), NaOMe or NaOH (2.1 eq.), MeOH
1 mL), rt.; NMR yield. Isolation yield > 90%.
NaOH
KOH
[e]
(
c
0
0.1
0.1
-
3
4
Quant.
Quant.
In the further experiments, various substrates including the penta-
acetyl/benzoyl-galactosides 3, glucosides 5 and mannosides 6, and
the methyl tetra-acetyl-galactosides 8,-glucosides 9,-
galactosides 12,-glucosides 13 and-mannosides 16, were
deacylated in methanol using 0.1 equiv. of NaOH and NaOMe
separately. It showed that (Table 2), irrespective of whether NaOH
or NaOMe was used, the deacetylated free glycosides were obtained
from the acetylated substrates in quantitative yields in 2 - 12 h.
Additional experiments were conducted to compare the use of NaOH
and NaOMe in the deprotection of benzyloxycarbonyl and pivaloyl
groups. All of the deprotections were completed in 2 h. In the case of
the deacylation of acetylated thio-containing glycosides, a little more
than a stoichiometric amount of the base is necessary for each
thioacetate group because the sulfhydryl group formed will
2
Na S
5
K
2
S
0.1
1
Quant.
6
7
8
Na
2
CO
3
0.1
0.1
0.2
4
4
8
Quant.
Quant.
Quant.
K
2
CO
3
CaO
c
9
MgO
0.2
24
-
1
/100
10/90
0/50
/100
10/90
0/50
0.5
1
24
0.5
1
Quant.
Quant.
d
d
1
0
1
NaOMe
NaOH
c
5
1
-
Quant.
Quant.
1
c
5
24
-
[
a]
[b]
Reagents and conditions: substrates (100 mg), MeOH (1 mL), rt.; NMR
[
c]
[d]
yield; uncompleted deacylation; bases (0.1 eq.), addition of water (1 -
5
0%).
2
| Green Chemistry, 2014, 00, 1‐3
This journal is © The Royal Society of Chemistry 2014

Page 3 of 29
Green Chemistry
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COMMUNICATION
neutralize the base. Therefore, 1.1 equiv. and 2.1 equiv. of NaOMe in Figure 3b: deacylation is catalyzed by the hydroxyl anion to form
were used in the deacetylation of penta-acetyl 1-thio-glucoside 20 an acetate anion, followed by esterification of methanol with the
View Article Online
and methyl tetra-acetyl 2,4-dithio-glucoside 22, producing free thio- acetate anion. However, as the esterification of methanol does not
DOI: 10.1039/C4GC02006E
glucosides in quantitative yields in 2 h, respectively. Testing NaOH occur when sodium acetate is dissolved in methanol, path b is also
with these substrates gave the same results. The results of all of these excluded. The above analyses indicate that transesterification
experiments indicate that the use of NaOH is identical to the use of catalyzed by hydroxyl cannot be explained by traditional base-
NaOMe. As the effects on deacylation of using NaOH in methanol catalysis principle.
and NaOMe in methanol are identical, it is reasonable that hydroxyl
anion resin is used in deacylation instead of NaOH. When hydroxyl
anion resin was used in the deacylation of each of compounds 3, 5, 6,
a)
-
-
MeOH + OH
MeO + H2O
O-
H O
-OH
O
2
R
8
2
, 9, 12, 13, 16, 18 and 19, all of the deacylations were completed in
-12 h. As hydroxyl anion resin is a catalyst, we hypothesized that it
R
R
HO
HO
MeO-
O
MeO
O
MeOAc
should be reused repeatedly in this process without time restrictions.
To test this assumption, we used hydroxyl anion resin (425 mg, 1
equiv. for the substrate but 0.2 eq. for each of the acetyl groups) to
deacetylate penta-acetyl glucoside 1 (100 mg) in 1 mL of methanol
with stirring. The first deacetylation was completed in 0.5 h. After
filtration, the resin was reused. The second deacetylation was
completed in 1 h. With repetition, the deacetylation extended the
reaction time to 2, 2.5, 3, 4 and 5 h, until the seventh deacetylation
b)
O-
AcOH AcO-
O
R
R
R
O
HO
O
HO-
AcOH
-
MeOH + AcO-
MeOAc + OH
(
a in Figure 2). We suspected that tiny chips of hydroxyl anion
Figure 3. Proposed two possible transesterification paths catalyzed by hydroxide
in light of traditional base‐catalysis principle.
chipped from the resin surface by stirring had reduced the catalytic
activity of the resin. Therefore, no stirring took place in the
subsequent experiments, during which deacetylation extended the
reaction time from 0.5 to 2 h, with repetition until the 10
deacetylation (b in Figure 2), confirming our conjecture.
Recently, a principle that hydrogen bonds between hydroxyl groups
and acetate anions involve the constitution of the rate-determining
transition state structure in pyridine catalyzed acetylation of
hydroxyl groups has been widely accepted with the theoretical
chemistry studies on the mechanism. In our previous studies, we
have developed new and improved reaction routes where
intermolecular non-covalent forces play key roles. The mechanism
studies also showed that the hydrogen bonds between hydroxyl
group and anions play key roles in the intramolecular acetyl group
migration and the regioselective acetylation catalyzed by acetate
anions . These results inspired us to propound that the H-bonds
th
5
OAc
O
OH
-OH resin
O
AcO
AcO
1
HO
HO
2
OH
6-8
OAc MeOH
OAc
OH
6
8
between hydroxyl groups and anions must also play key roles in
deacylation. Only the principle involving H-bond could perfectly
explain all our experimental results obtained in this study. Thus,
during deacylation catalyzed by NaOMe, an H-bond complex
…
..
-
[
MeOH OMe] may instantly form when a catalytic amount of
NaOMe is dissolved in methanol without considering about
solvation (a in Figure 4). Then the acetyl group is transformed into
methoxide through transition state a. During deacylation catalyzed
…
..
-
by NaOH, an H-bond complex [MeOH OH] may instantly form (b
in Figure 4). Then it has to be hypothesized that the energy barrier of
transition state b lower than that of transition state c so that the
acetyl group can be transformed into methoxide through transition
state b; otherwise the acetyl group would be transformed into
hydroxide through transition state c so as to restrain the catalytic
–
Figure 2. Deacetylation with the repeated reuse of a catalytic amount of OH‐
exchange resin.
The process by which hydroxyl anion catalyzes deacylation is of process. In order to support this, the theoretical calculations were
interest. According to the traditional base-catalysis principle (Figure performed (Figure S7). In order to simplify the calculation, the
2
1
a), there are only two possible reaction paths (Figure 3). One deacetylations of ethyl acetate catalyzed by methoxide and
3
possibility is the reaction path proposed by Goodman and shown in hydroxide in methanol were as models for DFT calculations without
Figure 3a: the hydroxyl anion first deprotonates methanol to form considering about solvation. The energy barrier of ethyl acetate with
…
.. …..
-
the methoxyl anion, followed by deacylation catalyzed by the [MeO
H OMe] for transesterification is 19.9 kcal/mol (Figure
…
.. …..
-
methoxide formed. If this were the case, the addition of water should 4a). The process with [MeO
H
OH] involves two pathways with
restrain the formation of methoxyl anion so as to stop the reaction. energy barriers of 18.4 and 21.1 kcal/mol, respectively, giving the
Thus, the experimental results of adding water (entries 10 and 11 in former process be preferred (Figure 4b).
Table 1) proved this path inefficient. The other possibility is shown
This journal is © The Royal Society of Chemistry 2014
Green Chemistry, 2014, 00, 1‐3 | 3

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Page 4 of 29
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COMMUNICATION
that the Zemplén condition has been misleading us for almost
9
0 years and methoxide can be completely VrieewpAlartciceledOnlbinye
hydroxide in the deacylation. The traditional base-catalyzed
DOI: 10.1039/C4GC02006E
mechanism can not be used to explain our results. We proposed
that H-bond play key roles in this base-catalyzed process. Both
kinetic isotope effect (KIE) studies and theoretical calculations
may support this principle. Therefore, hydroxyl anion
exchanged resin as a catalyst is used in deacylation instead of
NaOMe or NaOH which is fully supported by theory. The resin
can be repeatedly reused in the same process without additional
treatment. We believe that application of hydroxyl anion in
deacylation has great theoretical and practical significance in
both laboratory and industry settings. With the use of hydroxyl
+
anion resin in industry, the H -exchange columns in deacylation
may be reduced, and substantial savings may be made in terms
of equipment, materials and operations.
Acknowledgements
–
‐
This study was supported by the National Nature Science
Foundation of China (Nos. 21272083). The authors are also
grateful to Dr. Shitao Fu in the Analytical and Test Center of
Figure 4. Proposed transesterification paths catalyzed by OH and MeO via the
H‐bond complex.
It is known that an inverse secondary isotope effect would be led School of Chemistry & Chemical Engineering for support with
when the bending vibration of OH bonds in transition state become the NMR instruments.
9
more restricted. Clearly, the bending vibration of OH bonds in
transition states a and b, which are the rate-determining transition
Notes and references
a
state structures (Figure 4), become more restricted due to involving
H-bond, thus leading to inverse secondary isotope effects. Thus, an
inverse kinetic isotope effect (KIE) may give direct evidences to
support the H-bond involved principle. We chose two simple
molecules, ethyl benzoate and phenylmethyl acetate, as models, and
measured their KIE values through the measurement of their rate
constants for deacylation catalyzed separately by NaOH and NaOMe
in normal methanol and d-methanol (Figure S1-S4). For both of the
model molecules, the measured KIE values (k /k ) were less than
School of Chemistry & Chemical Engineering, Huazhong University of
Science & Technology, Luoyu Road 1037, 430074, Wuhan, P.R. China.
Fax: (+86) 27-87793242, E-mail: hdong@mail.hust.edu.cn.
b
Institute of Theoretical Chemistry, State Key Laboratory of Theoretical
and Computational Chemistry, Jilin University,Liutiao Road 2,
Changchun, 130023, P. R. China.
†
Supplementary Information (ESI) available: [General methods, general
method for measuring KIE values, Figure S1-S6, computational methods,
and Cartesian coordinates, energies and results of frequency calculations].
See DOI: 10.1039/c000000x/
H
D
0
.5 (Figure S3 and S4), irrespective of whether NaOH or NaOMe
1
was used, showing inverse secondary isotope effects. The H NMR
spectrum of deacylation catalyzed by NaOH showed only the esters
that functioned as starting materials (ethyl benzoate and
phenylmethyl acetate), the esters formed by transesterification
1
P. K. Kancharla, T. Kato, D. Crich, J. Am. Chem. Soc. 2014
,
136,
5
472; X. Meng, W. L. Yao, J. S. Cheng, X. Zhang, L. Jin, H. Yu, X.
Chen, F. S. Wang, H. Z. Cao, J. Am. Chem. Soc. 2014
,
136, 5205; S.
(
(
methyl benzoate and methyl acetate) and the alcohols produced
enthanol and phenylmethanol) (Figure S5 and S6). No acids formed
Y. Nie, W. Li, B. Yu, J. Am. Chem. Soc. 2014
, 136, 4157; B. J.
by hydrolysis could be seen, indicating that the outcomes of the
transesterifications were identical to those of NaOMe-catalyzed
deacylation.
In this study, all the yields reported were based on NMR analysis.
In order to demonstrate the potential for industry, penta-acetyl-
glucoside 1 (10g) were deacylated in methanol (100 mL) using 0.1
equiv. of NaOH (105 mg), KOH (144 mg) and hydroxyl anion resin
Beahm, K. W. Dehnert, N. L. Derr, J. Kuhn, J. K. Eberhart, D.
Spillmann, S. L. Amacher, C. R. Bertozzi, Angew. Chem. Int. Ed.
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2
3
4
,
.
(8.5 g) separately. After stirring at room temperature for 2 hours
L. A. Reed, III, P. A. Risbood, L. Goodman, J. Chem. Soc. Chem.
Commun. 1981, 760.
(
experiments in detail in SI), the free glucoses 2 were obtained in
9
2% (4.24 g), 97% (4.48 g) and 89% (4.1 g) isolation yields
V. Jaouen, A. Jegou, L. Lemee, A. Veyrieres, Tetrahedron 1999
245; L. Charon, J.-F. Hoeffler, C. Pale-Grosdemange, M. Rohmer,
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N. Tokitoh, T. Kawabata, Angew. Chem. Int. Ed. 2013 52, 6445; P.
, 55,
respectively.
9
.
,
Conclusions
.
5
We have shown that using NaOH in methanol and using
NaOMe in methanol for deacylation are identical. It indicates
,
4
| Green Chemistry, 2014, 00, 1‐3
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Page 5 of 29
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,
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2
,
,
2
,
This journal is © The Royal Society of Chemistry 2014
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View Article Online
DOI: 10.1039/C4GC02006E
Table of content:
-
We demonstrated OH as deacylation catalyst in methanol, indicating that Zemplén condition had
been misleading us for almost 90 years.

Page 7 of 29
Green Chemistry
View Article Online
DOI: 10.1039/C4GC02006E
Supporting Information
Zemplén Transesterification: A Name Reaction Having Been Misleading Us for 90
Years
a
b
b
a
a
Bo Ren , Meiyan Wang , Jingyao Liu , Jiantao Ge , Xiaoling Zhang and Hai
a,
Dong *
a
School of Chemistry & Chemical Engineering, Huazhong University of Science & Technology, Luoyu Road 1037,
4
30074, Wuhan, P.R. China, hdong@mail.hust.edu.cn
b
Institute of Theoretical Chemistry, State Key Laboratory of Theoretical and Computational Chemistry, Jilin
University, Liutiao Road 2, Changchun, 130023, P. R. China.
Contents
General methods
S2
General Method for Measuring KIE Value (Figure S1-2)
Figure S3 and S4
S12
S13
S14
S15
S16
S16
Figure S5 and S6
Computational methods and Figure S7
References
Cartesian coordinates and total energies
S1

Green Chemistry
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DOI: 10.1039/C4GC02006E
General methods: All commercially available starting materials and solvents were of
reagent grade and used without further purification. Chemical reactions were monitored
with thin-layer chromatography using precoated silica gel 60 (0.25 mm thickness) plates
(
0
CD
7
Macherey-Nagel). Flash column chromatography was performed on silica gel 60 (SDS
1
13
.040-0.063 mm). H NMR and C NMR spectra were recorded at 298K in CDCl
3
, D
2
O,
1
13
3
OD and d
6
-DMSO using the residual signals from CHCl
3
( H:  = 7.25 ppm; C:  =
1
1
13
7.2 ppm), D
2
O ( H:  = 4.80 ppm), CD OD ( H:  = 3.31 ppm; C:  = 49.1 ppm) and
3
1
13
1
d
6
-DMSO ( H:  = 2.50 ppm; C:  = 39.5 ppm) as internal standard. H peak
1
assignments were made by first order analysis of the spectra, supported by standard H-
1
H correlation spectroscopy (COSY).
General Deacylation Catalyzed by NaOH or NaOMe: carbohydrate substrates (100
mg) in dry methanol (1 mL) were added NaOH or NaOMe (0.1 eq.). The mixtures were
+
stirred at room temperature for 2 - 12 h, followed by ion exchange with H exchanged
resin. After being filtered, the filtrate was concentrated to afford the products. All the
products 2, 4, 7, 10, 11, 14, 15, 17 and 21 are known compounds.
-
General Deacylation Catalyzed by OH exchanged resin: carbohydrate substrates (100
-
mg) in dry methanol (1 mL) were added OH exchanged resin (85 mg). The mixtures
were stirred at room temperature for 2 - 12 h. After being filtered, the filtrate was
concentrated to afford the products.
Large Scale: penta-acetyl-glucoside 1 (10g) were deacylated in methanol (100 mL) using
0
.1 equiv. of NaOH (105 mg), KOH (144 mg) and hydroxyl anion resin (8.5 g) separately.
+
After stirring at room temperature for 2 hours, the reaction mixtures were treated with H
exchanged resin until neutrality (it is not necessary for reaction mixture with hydroxyl
anion resin as a catalyst). After being filtered, the filtrate was concentrated and
crystallized. The free glucoses 2 were obtained in 92% (4.24 g), 97% (4.48 g) and 89%
(4.1 g) yields respectively.
[
1]
1
3
-Thio-β-D-mannopyranose 21 : Compound 20 (101 mg, 0.25 mmol) was dissolved in
mL dry MeOH, and sodium hydroxide (11 mg, 0.27 mmol) in methanol (1 mL) was
added dropwise. After 40 minutes, the reaction mixture was neutralized with Amberlite
+
IR-120 H ion exchange resin, filtered, concentrated in vacuum, and lyophilized to
1
afford compound 2 (48.5 mg, 99%). H NMR (400 MHz, D O) δ = 5.05 (d, J = 1.0, 1H,
2
H-1), 4.26 (dd, J=1.0 Hz and 3.1 Hz, 1H, H-2), 4.00 (dd, J=2.2 Hz, 12.4 Hz, 1H, H-3),
3
=
.82 (dd, J = 5.9 Hz, 12.4 Hz, 1H, H-6), 3.74 (dd, J = 3.2 Hz, 9.6 Hz 1H, H-6’), 3.69 (t, J
9.4 Hz, 1H, H-4), 3.57–3.48 (m, 1H, H-5).
S2

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1
Methyl 2,4-thio-β-D-mannopyranoside 23: H NMR (400 MHz, CDCl
3
) δ = 4.51 (s, 1H,
H-1), 3.94 (dd, J = 12.2, 2.1, 1H, H-6), 3.83 (dd, J = 4.6 Hz and 12.2 Hz, 1H, H-6’), 3.57
m, 2H, H-2, H-3), 3.48 (s, 3H, OMe), 3.35 (s, 1H, OH), 3.29–3.21 (m, 1H, H-5), 3.12 –
(
2
1
.97 (m, 1H, H-4), 2.77 (s, 1H, OH), 1.72 (d, J = 6.3 Hz, 1H, SH), 1.59 (d, J = 8.2 Hz,
1
3
3
H, SH). C NMR (100 MHz, CDCl ) δ = 100.8, 78.6, 74.0, 62.6, 57.1, 47.3, 39.4.
+
HRMS (ESI-TOF) m/z: [M + Na] Calcd for C H O S Na 249.0231; found 249.0226.
7
14
4 2
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1
1
Comparison of H NMR spectrum (H peak) of crude product from deacylation with
that of reagent grade sample indicating a quantitative NMR yield: carbohydrate
substrates (100 mg) in dry methanol (1 mL) were added NaOH (0.1 eq.). The mixtures
+
were stirred at room temperature for 2, followed by ion exchange with H exchanged
resin. After being filtered, the filtrate was concentrated and directly tested by NMR
instrument.
Deacylation of compound 3 (tested in D
2
O): a) reagent grade sample; b) crude product.
a
b
H
1β
H
1α
a
H
1β
H
1α
b
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2
Deacylation of compound 5 (tested in D O): a) reagent grade sample; b) crude product.
a
b
H
1β
H
1α
a
H
1β
H
1α
b
S5

Green Chemistry
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2
Deacylation of compound 6 (tested in D O): a) reagent grade sample; b) crude product.
a
b
H
1α
H
1β
a
b
H
1α
H
1β
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Deacylation of compound 8 (tested in d
6
-DMSO): a) reagent grade sample with
2
addition of a drop of D O; b) reagent grade sample; c) crude product.
a
b
c
a
H
1
b
c
H
1
H
1
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Green Chemistry
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Deacylation of compound 12 (tested in d
6
-DMSO): a) reagent grade sample with
2
addition of a drop of D O; b) reagent grade sample; c) crude product.
a
b
c
H
1
a
H
1
b
c
H
1
S8

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DOI: 10.1039/C4GC02006E
Deacylation of compound 13 (tested in d
6
-DMSO): a) reagent grade sample with
2
addition of a drop of D O; b) reagent grade sample; c) crude product.
a
b
c
H
1
a
H
1
b
c
H
1
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Green Chemistry
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Deacylation of compound 16 (tested in d
6
-DMSO): a) reagent grade sample with
2
addition of a drop of D O; b) reagent grade sample; c) crude product.
a
b
c
H
1
a
H
1
b
H
1
c
S10

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DOI: 10.1039/C4GC02006E
6
Deacylation of compound 9, 18 and 19 (tested in d -DMSO): a) reagent grade
2
sample with addition of a drop of D O; b) reagent grade sample; c) crude product for
compound 18; d) crude product for compound 19; e) crude product for compound 9.
a
b
c
d
e
H
1
a
H
1
b
H
1
c
H
1
d
H
1
e
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General Method for Measuring KIE Value: As step b) is the rate-determining step,
the rate constants can be measured using the following equation: ln (B /B) = k*A*t,
where A stands for the concentration of base catalysts, B stands for the concentration
of esters, k stands for the rate constant, and t is the reaction time. The values of B /B
0
0
can be measured over time using 1H NMR tests. In Figure S1, A stands for the
concentration of the H-bonding complex and X stands for MeO or OH group. As
methanol acts as solvent in the reaction, A equals to the concentration of hydroxyl
anion or methoxyl anion and is a constant. Therefore, we can get the differential
equation (1) which is related to the rate constant k and the concentration of the esters
(
0
B). To solve the differential equation (1) gets equation (2). B stands for the initial
concentration of the esters in equation (2). Therefore, the value of k can be measured
through recording the concentration of the esters (B) with time (t).
Figure S1. The value of k can be measured via recording the concentration of the esters (B) with time (t).
a)
b)
O
O
O
O
R
R
R
R
H C O
O
O
O
O
3
-
CH O
CH3O
3
H C O
3
HOCH3
HOCH3
O
O
O
O
O
R
R
R
R
O
O
O
D C O
3
-
CD O
CD3O
3
D C O
3
DOCD3
DOCD3
Figure S2. Inverse isotope effect supporting H-bond involved transesterification mechanism. a) The
traditional base-catalyzed transesterification mechanism should not lead to isotope effect since no hydrogen
atom is involved in the reaction. b) The proposed H-bond involved transesterification mechanism should
lead to an inverse isotope effect as the case involving conversion of a dicoordinate COH bond to a
tricoordinate transition state.
S12

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DOI: 10.1039/C4GC02006E
a)
b)
Figure S3. The values of k were measured for transesterification of ethyl benzoate in methanol. a) NaOH
-
5
2
-4
2
(
=
0
0.1 eq.) as catalyst, k
0.42; b) NaOMe (0.1 eq.) as catalyst, k
.9980, therefore, k /k = 0.44.
H
*A = 5.035 x 10 /s, R = 0.9953, k
D
*A = 1.189 x 10 /s, R = 0.9963, therefore, k
H
/k
D
-
5
2
-5
2
H D
*A = 3.971 x 10 /s, R = 0.9962, k *A = 9.057 x 10 /s, R =
H
D
Transesterification of phenylmethyl acetate
5
NaOH in methanol
NaOH in d-methanol
4
3
2
1
0
0
1000
2000
3000
4000
reaction time (t/s)
a)
b)
Figure S4. The values of k were measured for transesterification of phenylmethyl acetate in methanol. a)
-
4
2
-3
2
NaOH (0.02 eq.) as catalyst, k
therefore, k /k = 0.39; b) NaOMe (0.02 eq.) as catalyst, k
x 10 /s, R = 0.9944, therefore, k /k = 0.40.
H
*A = 4.277 x 10 /s, R = 0.9995, k
D
*A = 1.102 x 10 /s, R = 0.9997,
-4 2
H
D
H
*A = 3.371 x 10 /s, R = 0.9952, k
D
*A = 8.406
-
4
2
H
D
S13

Green Chemistry
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DOI: 10.1039/C4GC02006E
Figures S5. Recorded transesterification of ethyl benzoate in methanol catalyzed by NaOH with time. *
stands for the methyl peak of the formed methyl benzoate.
Figures S6. Recorded transesterification of phenylmethyl acetate in methanol catalyzed by NaOH with time.
*
stands for the methyl peak of the formed methyl acetate.
S14

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DOI: 10.1039/C4GC02006E
Computational methods
Molecular geometries of all species were optimized without constraints via DFT
2
calculations using the B3LYP functional. The 6-31+G(d,p) basis set was used for C, H
and O atoms. Frequency calculations were carried out at the same level of theory to
identify the stationary points as minima (zero imaginary frequencies) or transition states
(
2
one imaginary frequency), and to provide the thermal correction to free energies at
98.15 K. Intrinsic reaction coordinates (IRC) were calculated for all transition states to
3
confirm that the structures indeed connect two relevant minima. To take the solvent effect
4
into account, single-point energy calculations were performed at the level using 6-
5
3
11++G(d,p) basis set for all the atoms with continuum solvent model SMD in methanol.
The solvation- and entropy-corrected relative free energies are used to analyze the
reaction mechanism. All calculations were performed with the Gaussian 09 software
6
package.
Figure S7. The possible four approaches for transesterification of ethyl acetate in methanol with hydroxide as a
…
.. …..
-
….. …..
-
catalyst. a) Process through [MeO
H
OMe] , b) Process through [HO
H
OH] ), and (c) and (d) Process
…
.. …..
-
through [MeO
H
OH] . The energy values are all in kcal/mol.
S15

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DOI: 10.1039/C4GC02006E
References
1
.
.
Floyd, N.; Vijayakrishnan, B.; Koeppe, J. R.; Davis, B. G. Angew. Chem. Int. Ed. 2009, 48, 7798-
802.
(a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648. (b) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H.
Chem. Phys. Lett. 1989, 157, 200. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785.
(a) Fukui, K. J. Phys. Chem. 1970, 74, 4161. (b) Fukui, K. Acc. Chem. Res. 1981, 14, 363.
Zhao, Y.; Truhlar, D. G.; Theor. Chem. Acc. 2008,120,215.
7
2
3.
4.
5.
6.
Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys. Chem. B 2009, 113, 6378.
Frisch, M. J. In Gaussian 09, revision A.02; Gaussian, Inc., Wallingford, CT, 2009.
Cartesian coordinates and free energies for all calculated species
…
.. …..
-
[MeO
H OMe]
G = -230.8599036 a.u.
O
H
O
C
H
H
H
C
H
H
H
-1.89974
-2.46805
-3.08995
-4.44179
-4.73002
-4.83839
-5.05843
-1.45089
-1.66698
-1.91035
-0.35002
2.09015
3.10467
4.19558
4.01880
2.95125
4.55716
4.38645
1.92551
1.43042
1.53166
1.59961
1.40981
1.27105
0.51294
2.26668
0.13224
2.80574 -0.50815
1.04713 -0.37893
1.76271
0.07653
…
.. …..
-
[MeO
H OH]
G = -191.6143201 a.u.
O
H
H
O
C
H
H
H
-2.01494
-1.49473
-2.48158
-3.04463
-4.38326
-5.04614
-4.71164
-4.73121
1.86227
2.03812
2.81623
4.10075
4.17241
3.94761
5.18669
3.46758
1.46947
2.26187
1.26110
1.07202
1.33977
0.45975
1.68777
2.14102
…
.. …..
-
[EtO
H OMe]
G = -270.1265687 a.u.
O
H
O
C
H
H
H
C
H
H
C
H
H
H
-1.70435
-2.49373
-3.13405
-4.28341
-4.07208
-4.91612
-4.90950
-0.59608
-0.49593
0.36012
-0.56592
0.34694
-1.44144
-0.61101
2.57110 -2.51352
3.61302 -2.04734
4.40369 -1.66560
3.83298 -1.12849
3.08767 -0.33425
4.61683 -0.67326
3.31317 -1.88369
2.31896 -1.75442
3.01715 -0.88489
2.44364 -2.32954
0.88184 -1.17568
0.69362 -0.58400
0.71665 -0.53379
0.15013 -1.99339
S16

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…
.. …..
-
[EtO
H OH]
G = -230.8823468 a.u.
O
H
O
C
H
H
C
H
H
H
H
-1.84705
-2.61782
-3.17004
-0.58155
-0.23345
0.18604
-0.41076
0.62615
-1.08321
-0.68315
-3.14304
2.52771 -2.25556
3.43202 -1.42103
4.15222 -0.86377
2.27044 -1.81889
2.98624 -1.02745
2.35759 -2.63569
0.84850 -1.22141
0.65997 -0.89047
0.72107 -0.36302
0.09446 -1.97224
4.93466 -1.42602
MeC(O)OEt
G = -307.5288120 a.u.
C
O
C
H
H
H
O
C
H
H
C
H
H
H
-1.85776
-1.28541
-3.34453
-3.53994 -0.47796 -0.86388
-3.82588 -0.08679 0.85818
-3.76050
-1.22222
0.21584
0.37122
0.15062
0.24169 -0.06285
0.16603
1.21493
1.20350 -0.37868
0.77144 -0.95897
0.93366 -0.86721
0.65588 -0.02278 -0.56821
0.43499
0.71294
1.79944
0.48046
0.25723
1.66276 -0.08100
1.39149 -2.22580
1.52562 -2.19389
0.65296 -2.99922
2.34492 -2.51023
MeC(O)OMe
G = -268.2592136 a.u.
C
O
C
H
H
H
O
C
H
H
H
-1.88836
-1.25549
-3.38277
-3.61039 -0.45107 -0.83267
-3.81374 -0.17322 0.92228
-3.82351
-1.31698
0.11319
0.60505
0.38608
0.39267
0.35269
0.05545
0.21972
0.16382
1.15685
0.00163
1.19369 -0.23214
0.85447 -0.95639
1.02218 -0.91380
0.06060 -0.74710
1.43110 -1.88644
1.71095 -0.11269
MeC(O)OH
G = -229.0124747 a.u.
C
O
C
H
H
H
O
H
-1.88827
-1.15669
-3.38191
-3.65229 -0.39147 -0.85659
-3.71871 -0.29542 0.92942
-3.87488
-1.41856
-0.45580
0.38991
0.04693
0.20345
0.07352
0.97827
0.02129
1.17549 -0.07808
1.00802 -1.04227
1.09300 -0.93669
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TSa1
G = -538.3571985 a.u.
C
O
C
H
H
H
O
C
H
H
C
H
H
H
O
O
H
C
H
H
H
C
H
H
H
-1.61986
-1.65068
-2.88511 -0.62032 -0.33192
-2.65520 -1.50060 -0.93660
0.13532
1.06329
0.05921
0.89016
-3.40462 -0.92943
0.57789
-3.53846
-0.82287
0.37868
0.97802
0.14563
1.13199
2.06293
1.38692 -0.00776 -2.55272
0.52500 1.47074 -3.03605
-0.70471 -1.31215 0.80714
1.14075 -2.64210 -0.48839
0.45121 -2.10641
-0.52937 -1.19633
-1.16486 -1.90722
0.51984 -1.39507
-0.78415 -0.17555
0.49297 -3.22378 -1.59133
1.24784 -3.71756 -2.22045
-0.24605 -3.99072 -1.29428
-0.03303 -2.47746 -2.20860
0.05363 -0.90334
0.26222 -1.10798
0.99805 -0.92200
0.51343 -0.14038
2.01724 -0.58520
1.01185 -2.24588
1.58591 -2.14850
0.02329
2.18216
2.75334
2.47809
2.51846
Inta1
G = -538.3600854 a.u.
C
O
C
H
H
H
O
C
H
H
C
H
H
H
O
O
H
C
H
H
H
C
H
H
H
-1.5149
-1.59274
-2.80721 -0.67200 -0.32443
-2.60233 -1.56317 -0.92560
0.03605
1.05244
0.10718
0.85051
-3.36530 -0.95987
0.57159
-3.41603
-0.71939
0.45147
1.16786
0.19919
1.05946
1.97311
1.31879
0.35124
0.02831 -0.90940
0.14368 -1.10885
0.92708 -0.96567
0.41170 -0.30747
1.88666 -0.49526
1.13656 -2.34859
1.74242 -2.27953
0.17749 -2.81159
1.65222 -3.00850
-0.68217 -1.20876
1.05075 -2.88115 -0.34324
0.84771
0.42689 -2.24633
-0.63951 -1.12016
-1.41417 -1.74948
0.34251 -1.46221
-0.79524 -0.07802
0.49191 -3.21284 -1.59478
1.26745 -3.70244 -2.20007
-0.35506 -3.91701 -1.50390
0.13428 -2.32337 -2.13285
0.10590
2.24544
2.72795
2.61190
2.56063
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Inta2
G = -538.3588040 a.u.
C
O
C
H
H
H
O
C
H
H
O
O
H
C
H
H
C
H
H
H
H
C
H
H
H
-1.75817
-1.94113
-2.88218 -0.81975
-2.52963 -1.63947
-3.27296 -1.22605 -0.75236
-3.68589 -0.28059
-1.16680
-0.17382
0.71096
-0.55060
-0.54337 -0.94156 -0.70658
0.16648 -0.13951
1.08622 -0.97414
0.18377
0.81549
0.70137
1.13452
1.04749
0.50608
0.53388
0.51175
1.51225
1.14467
2.40605
0.64255 -2.82746
0.18554 -2.14345
-0.10440 -0.71542 -2.01356
1.00295 -0.68673 -2.03483
0.76690
0.19857
-0.46863
0.27073 -2.34416
1.14461 -2.17480
2.06987 -1.60753
1.38727 -2.93600
0.41409 -1.47442
1.91115
1.70108
2.66611
2.34065
2.07535
0.11253
1.76494
-0.59008 -1.79501 -2.99489
-1.68560 -1.80116 -3.03817
-0.20563 -1.60852 -4.00955
-0.25643 -2.79009 -2.67564
TSa2
G = -538.3569332 a.u.
C
O
C
H
H
H
O
C
H
H
O
O
H
C
H
H
C
H
H
H
H
C
H
H
H
-1.91700
-2.07880
-3.01838 -0.70656
-2.65185 -1.52276
-3.38907 -1.11243 -0.70924
0.30623 -0.06522
1.20631 -0.91661
0.23453
0.86165
-3.84061 -0.19167
0.74931
1.19316
1.10477
0.54081
0.61351
-1.32284
-0.32219
0.54574
-0.69979
-0.64515 -0.84985 -0.64370
0.52025 -2.72830
0.06807 -2.03959
-0.20644 -0.61916 -1.94483
0.90180 -0.56501 -1.97101
-0.58786
0.64494
1.63999
1.26966
2.54558
0.81639
0.24202
0.35926 -2.28473
1.03881 -2.07408
1.95992 -1.50464
1.29477 -2.83280
0.31457 -1.37403
1.95044
1.72660
2.70395
2.39255
2.13182
-0.01706
1.87096
-0.66484 -1.70882 -2.93059
-1.76008 -1.74078 -2.97602
-0.28263 -1.51323 -3.94468
-0.30941 -2.69610 -2.61043
S19

Green Chemistry
Page 26 of 29
View Article Online
DOI: 10.1039/C4GC02006E
TSb1
G = -499.1153172 a.u.
C
O
C
H
H
H
O
O
H
O
H
C
H
H
C
H
H
H
C
H
H
H
-1.73665
-1.74818
-2.96020 -0.33543 -0.51779
-2.68841 -1.05023 -1.29558
-3.47462 -0.85744
-3.63604
-0.89426
0.35501
0.97348
0.05244
1.12107
0.29108
0.42636 -0.93457
0.74063 -0.99346
-0.70999 -1.39111
0.42507
-0.17492 -2.60107 -2.16566
-0.50325 -3.17012 -1.46001
-0.60041 -2.52440 -0.67404
-0.70029 -1.72629
-1.39980 -2.55679
-0.98876 -0.85952
0.33292
0.13455
0.84095
1.76460
2.01962
2.39295
1.33053 -0.57556
2.25135 -0.01114
0.62244
0.09004
2.11386
0.30481 -2.05347
1.16207
2.11849
1.37215
0.63340
1.61711 -1.82025
2.07889 -1.54264
0.69134 -2.36697
2.29999 -2.49624
Intb1
G = -499.1166832 a.u.
C
O
C
H
H
H
O
O
H
O
H
C
H
H
C
H
H
H
C
H
H
H
-1.59163
-1.62289
-2.92307 -0.44987 -0.45939
-2.77603 -1.20230 -1.24064
-3.55064 -0.87104
-3.43348
-0.73672
-0.89605 -1.35276
-0.16609 -1.51231 -2.03807
0.01031 -2.43279 -1.78145
-0.24250 -2.36146 -0.83636
-1.01549 -1.61825
-1.95991 -2.14285
-0.98170 -0.68374
0.00843
0.88280
0.16107
1.07634
0.33321
0.42249 -0.88333
0.31841 -1.02420
0.62263
1.99490
2.24301
2.57144
0.45997
0.23719
1.17051
1.00013 -0.69755
1.79996 0.02032
0.30908 -0.21479
2.30144
1.56693 -1.97895
2.10886 -1.75876
0.76960 -2.69500
2.26063 -2.46024
-0.18110 -2.26750
1.06441
1.99447
1.29806
0.36473
Intb2
G = -499.1148689 a.u.
C
O
C
-1.79481
-1.86051
-3.06978 -0.30128
0.01979 -0.10638
0.79678 -1.09982
0.68408
S20

Page 27 of 29
Green Chemistry
View Article Online
DOI: 10.1039/C4GC02006E
H
H
H
O
O
H
O
H
C
H
H
C
H
H
H
C
H
H
H
-2.88798 -1.03894
-3.81843 -0.69257 -0.01037
1.47179
-3.44615
-0.80648
0.62467
0.39173
1.13355
0.94917
-1.28186 -1.47358 -0.50477
-0.13990 -1.39668
-0.05892 -2.33062
-0.46138 -2.27103
-0.83471 -1.62788 -1.82650
-0.92538 -0.66168 -2.34390
0.23363 -1.91792 -1.82898
-1.64757 -2.69618 -2.56896
-1.26531 -2.84273 -3.59045
-1.60292 -3.65830 -2.04329
-2.69917 -2.39319 -2.63256
2.08062
1.83023
0.93321
0.37818
0.14983
0.93576
1.00776
0.95866
1.75084 -0.29333
1.37622 1.27862
0.20153 -0.06475
0.43075
TSb2
G = -499.1138356 a.u.
C
O
C
H
H
H
O
O
H
O
H
C
H
H
C
H
H
H
C
H
H
H
-1.85664
-1.82927
-3.13726 -0.17821
-2.93705 -0.96683
-3.80468 -0.55976 -0.14022
-3.61668
-0.89719
-1.24703 -1.59292 -0.48317
0.01659 -1.62043
0.11454 -2.44220
-0.38192 -2.21220
-0.84439 -1.72688 -1.79562
-0.98156 -0.76843 -2.33777
0.24152 -1.97243 -1.87281
-1.62641 -2.82337 -2.54818
-1.28554 -2.91907 -3.59184
-1.50107 -3.79358 -2.05061
-2.69735 -2.58413 -2.55261
0.35687
0.24183
0.97197
0.83323
0.29893 -0.02215
0.94210 -1.07603
0.63339
1.36047
0.67356
0.53355
1.13759
0.97868
2.09846
1.60142
0.75044
0.98858
1.89215 -0.12050
1.20186 1.36898
0.20555 -0.11275
0.48900
TSc1
G = -499.1102010 a.u.
C
O
C
H
H
H
O
C
H
-1.89175
-1.76246
-3.11967 -0.40172 -0.14948
-2.93872 -0.95168 -1.07426
-3.37155 -1.10256
-3.95678
-1.36384
-0.18041
0.49004
0.38964
0.88275
0.26604
1.39546
0.64744
0.29710 -0.29444
1.02528 -0.85666
1.78379 -0.61668
1.19590
0.01874
S21

Green Chemistry
Page 28 of 29
View Article Online
DOI: 10.1039/C4GC02006E
H
C
H
H
H
O
O
H
H
C
H
H
H
-0.43343
0.46962
1.36351
0.77071
-0.22174
-0.65597 -1.21607
1.31376 -1.55128 -1.36225
0.54083 -1.38789 -0.69280
2.71090 -0.08226
2.07310 -1.96241
2.69583 -1.82463
1.13421 -2.43705
2.60548 -2.62759
0.23544
-0.40409 -1.21101
1.16795
0.90518 -2.53909 -2.26542
0.00742 -2.24746 -2.84162
1.71600 -2.72430 -2.98744
0.67321 -3.50193 -1.77223
Intc1
G = -499.1161756 a.u.
C
O
C
H
H
H
O
C
H
H
C
H
H
H
O
O
H
H
C
H
H
H
-1.56645
-1.63397
-2.88283 -0.62263 -0.32908
-2.70946 -1.55185 -0.88351
0.01738
1.08916
0.14841
0.84483
-3.50304 -0.83462
0.54689
-3.40535
-0.75806
0.40904
1.20324
0.18760
0.88226
1.80301
1.08713
0.11418
-0.85932 -1.09845
0.97251 -2.89382
0.32940 -2.23347
-0.62426 -0.60439
0.08967 -0.97620
0.09854 -1.10514
0.88454 -0.99090
0.32315 -0.46803
1.78084 -0.39594
1.26376 -2.39210
1.86167 -2.34255
0.36964 -2.99343
1.85022 -2.91029
0.95088
0.00238
0.36626
1.74906
0.57458 -3.19169 -1.32038
0.25697 -2.29064 -1.86221
1.42976 -3.63992 -1.84447
-0.25627 -3.91927 -1.35154
Intc2
G = -499.1153200 a.u.
C
O
C
H
H
H
O
O
O
H
H
C
H
H
C
-1.36314 -0.08706 -0.12478
-1.28135 0.93092 -0.89120
-2.75192 -0.54234
-2.69847 -1.44153
0.35027
0.97318
-3.37617 -0.74594 -0.52466
-3.19902
-0.51802
0.27184
0.03883
0.93028
1.08341
-0.82880 -1.42146 -0.78869
-0.43625 -3.58375
-0.61022 -2.80510
0.83685
0.24740
0.88565
-0.04613
0.86038
0.28264 -1.23156 -1.63544
0.23560 -0.21373 -2.04617
1.22750 -1.32457 -1.06678
0.25896 -2.26840 -2.75885
S22

Page 29 of 29
Green Chemistry
View Article Online
DOI: 10.1039/C4GC02006E
H
H
H
C
H
H
H
1.13242 -2.14916 -3.41632
0.26995 -3.28732 -2.35392
-0.64910 -2.15191 -3.36179
0.40026 -3.15439
0.19179 -3.77323
1.47061 -3.27754
0.22686 -2.10036
1.89488
2.77953
1.64807
2.14414
TSc2
G = -499.1094938 a.u.
C
O
C
H
H
H
O
O
O
H
H
C
H
H
C
H
H
H
C
H
H
H
-1.42885
-0.97817
-2.82662 -0.48380 -0.13769
-2.95224 -1.46071 0.33328
-2.99585 -0.57316 -1.21209
-3.55865
-1.12533 -0.04281
-0.47428 -1.51223 -0.47066
0.94315 -2.69056
0.40306 -2.21530
0.06785
1.03466 -0.53983
0.10022
0.22119
0.28138
1.46971
1.39113
0.67686
1.55505
-0.25011
0.36309
0.26047 -1.31017 -1.63225
0.31599 -0.22751 -1.85548
1.30510 -1.66108 -1.50048
-0.33766 -2.03947 -2.85107
0.27092 -1.87629 -3.75464
-0.39647 -3.11908 -2.66216
-1.35344 -1.67683 -3.05156
0.03828 -3.22911
-0.55291 -4.06554
0.60762 -3.62297
-0.67029 -2.47355
2.32223
1.90435
3.17719
2.69642
S23