Glucosamine condensation catalyzed by 1-ethyl-3-methylimidazolium acetate: Mechanistic insight from NMR spectroscopy

Article abstract of DOI:10.1039/c5cp02169c

The basic ionic liquid 1-ethyl-3-methylimidazolium acetate ([C₂C₁Im][OAc]) could efficiently catalyze the conversion of 2-amino-2-deoxy-D-glucose (GlcNH₂) into deoxyfructosazine (DOF) and fructosazine (FZ). Mechanistic investigation by NMR studies disclosed that [C₂C₁Im][OAc], exhibiting strong hydrogen bonding basicity, could coordinate with the hydroxyl and amino groups of GlcNH₂via the promotion of hydrogen bonding in bifunctional activation of substrates and further catalyzing product formation, based on which a plausible reaction pathway involved in this homogeneous base-catalyzed reaction was proposed. Hydrogen bonding as an activation force, therefore, is responsible for the remarkable selectivity and rate enhancement observed.

Full text of DOI:10.1039/c5cp02169c

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DOI: 10.1039/C5CP02169C.
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Page 1 of 23
Physical Chemistry Chemical Physics
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DOI: 10.1039/C5CP02169C
Glucosamine
condensation
catalyzed
by
1ꢀethylꢀ3ꢀmethylimidazolium acetate: mechanistic insight from
NMR spectroscopy
Lingyu Jia,ab Christian Marcus Pedersen,c Yan Qiao,d Tiansheng Deng,a Pingping
Zuo,d Wenzhi Ge,ab Zhangfeng Qin,d Xianglin Hou,*a and Yingxiong Wang*a
a
The Biorefinery Research and Engineering Center, Institute of Coal Chemistry,
Chinese Academy of Sciences, Taiyuan, People’s Republic of China.
Eꢀmail: houxl@sxicc.ac.cn, wangyx@sxicc.ac.cn; Fax: +86 351 4041153; Tel: +86
351 4049501
b Graduate University of Chinese Academy of Sciences, Beijing, People’s Republic of
China
c
Department of Chemistry, University of Copenhagen, Universitetsparken 5,
DKꢀ2100 Copenhagen Ø, Denmark
d
State Key Laboratory of Coal Conversion, Institute of Coal Chemistry, Chinese
Academy of Sciences, Taiyuan, People’s Republic of China
Abstract
The basic ionic liquid 1ꢀethylꢀ3ꢀmethylimidazolium acetate ([C2C1Im][OAc])
could efficiently catalyze the conversion of 2ꢀaminoꢀ2ꢀdeoxyꢀDꢀglucose (GlcNH2)
into deoxyfructosazine (DOF) and fructosazine (FZ). Mechanistic investigation
by NMR studies disclosed that [C2C1Im][OAc], exhibiting strong hydrogen
bonding basicity, could coordinate with the hydroxyl and amino groups of
GlcNH2 via the promotion of hydrogen bonding in bifunctional activation of
substrate and further catalyzing products formation, based on which a plausible
reaction pathway involved in this homogeneous baseꢀcatalyzed reaction was
proposed. Hydrogen bonding as an activation force, therefore, is responsible for
the remarkable selectivity and rate enhancement observed.
Introduction
Concerns about global warming and energy security have directed researchers’ focus
on the use of biomass as alternative feedstocks to fossil resources for a variety of
chemicals and fuels.1ꢀ4 Chitin biomass, being the second most abundant class of
1

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biopolymers (after the cellulose) on earth with an estimated global production of
around 1×1010 tons each year, has attracted considerable attention as a sustainable and
costꢀeffective organic nitrogen resource.5ꢀ10 However, strategies for the utilization of
biologically or chemically fixed nitrogen has not been fully exploited. The most
abundant amino sugar, 2ꢀaminoꢀ2ꢀdeoxyꢀDꢀglucose (GlcNH2), as the monomer unit of
polysaccharide chitosan, has an underestimated but remarkable potential for the
production of renewable, valueꢀadded chemicals, especially Nꢀcontaining compounds
with potential pharmacological and biological activities (Scheme 1).11ꢀ13 Direct
conversion of GlcNH2 into high valued chemicals bearing nitrogen in high yields is
therefore a topic of increasing interest.
Scheme 1 A oneꢀpot dehydration process to convert GlcNH2 into DOF and FZ
promoted by the basic imidazolium ionic liquid [C2C1Im][OAc].
A major driving force for the development of ionic liquids (ILs) is the desire for
greener chemical synthesis, which has aroused great interests both in academia and
industry. ILs are often found to be a “greener” alternative to volatile organic solvents,
and to have better properties than conventional solvents.14ꢀ16 Efforts have been
devoted to explore the dissolution mechanism of cellulose in ILs.17ꢀ20 However,
applications involving ILs are far beyond being just convenient “alternative” solvents,
and thus numerous investigations are to explore their potential as effective catalysts
for chemical reations.10,19,21ꢀ27 The acidic and neutral ILs have been well recognized
and successfully applied in many organocatalysis.21ꢀ27 However, the basic ILs for the
carbohydrates conversions were scarcely studied. 1ꢀEthylꢀ3ꢀmethylimidazolium
acetate, [C2C1Im][OAc] (Scheme 1), has emerged as one of the most promising
candidates for performing chemical reactions in the context of Green Chemical
2

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synthesis due to its nonꢀtoxicity and biodegradability.16,18,19 More importantly,
[C2C1Im][OAc] with strong hydrogen bond basicity has been widely introduced as
more environmentally benign reaction medium for the homogeneous physical or
chemical modification of the polysaccharide with high efficiency.18,19,21,28ꢀ31 Although
[C2C1Im][OAc] display high activity, to our knowledge there have been no reports of
the use of [C2C1Im][OAc] as catalysts for the conversion of chitin biomass. Another
interesting effect of using ILs is the change in reaction mechanism/pathway which
might occur and hence led to changes in product formation, yields and ratios.32ꢀ34
Despite the ongoing wide interest in ILs, the nature of the catalystꢀsubstrate
interactions and the mechanism of in situ catalytic reaction pathways using basic ILs
is not fully understood and only sporadically investigated.
It is reported that the main contribution to the carbohydrates–ILs interaction energy
comes from favorable hydrogen bonding interactions between hydroxyl groups of
carbohydrates and the cation or anion of the ILs.18,28ꢀ31,35 Studies have additionally
shown that the catalytic efficiency of [Bmim][OAc] predominantly stemmed from
hydrogen bonding interactions, which are considered as the key intermediate state for
further conversion.32 The catalyst and substrate binding via the promotion of
hydrogen bonding is the key point for this remarkable catalytic performance. Thus,
ILs with specific hydrogenꢀbond donor/acceptor groups should enhance the ability of
ILs to interact with the substrate, which favor ILsꢀsubstrate interactions and hence
activation. These observations suggest that [C2C1Im][OAc] could specifically
coordinate with the hydroxyl and amino groups on GlcNH2 due to its strong hydrogen
bonding basicity. Our earlier investigations resulted in the development of [Bmim]OH
as a dual solventꢀcatalyst for the synthesis of nitrogen heterocycles from bioꢀbased
carbohydrate GlcNH2.13 Therefore, [C2C1Im][OAc], similar to the [Bmim]OH,
displaying strong basicity, may play the same role in catalyzing conversion of GlcNH2
to pyrazine derivatives. Herein, we report using [C2C1Im][OAc] as the reaction
medium to produce deoxyfructosazine (DOF) and fructosazine (FZ) from GlcNH2
3

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with high selectivity and rate enhancement in a single step. However, it is unclear
how [C2C1Im][OAc] catalyze biomass transformations. The modes of action of
[C2C1Im][OAc] on chitin biomass degradation need to be elucidated in order to
develop and improve the catalysis process. To better understand the underlying
mechanism of catalysis by [C2C1Im][OAc] at a molecular level, we turned to NMR
spectroscopy, which has been widely employed to characterize biomass conversion
processes.7,36 Hydrogen bonding interactions of [C2C1Im][OAc], which were
responsible for the selective conversion of GlcNH2 via homogeneous catalysis, were
elucidated for the first time at a molecular level.
Results and discussion
An initial NMR study showed that HClꢀfree GlcNH2, when dissolved in DMSOꢀd6,
exhibit sufficient resolution to clearly identify distinct proton resonances of the
1
hydroxyl and amino groups and carbon signals in the H and 13C NMR spectra,
respectively (Fig. S1ꢀS2, ESI†). The assignment of proton and carbon signals was
obtained according to the literature and the 2D homoꢀ or heteroꢀ NMR spectra (Fig.
S3ꢀS5, ESI†).11 Surprisingly, when a catalytic amount of [C2C1Im][OAc] (molar ratio
of [C2C1Im][OAc]/GlcNH2 = 0.1) was added to the GlcNH2/DMSOꢀd6 solution, the
peaks of the hydroxyl and amino groups quickly merged together and a new broad
1
peak was observed in the H NMR spectra (Fig. S6, ESI†). Interestingly, when the
molar ratio of [C2C1Im][OAc]/GlcNH2 was increased, the peak gradually moved
downfield (Fig. 1). As it is known that traces of acid or base catalyzes proton
exchange, the significant broadening of these proton resonance of the hydroxyl and
amino groups is mainly due to the intermolecular proton exchange.29,39 Presumably,
the aromatic protons in the imidazolium cation, especially the most acidic H2,
interacts with the oxygen or nitrogen atoms of the hydroxyl and amino groups and
hence speed up the proton exchange rate. Lower field shift of the proton resonances of
hydroxyls and amino was ascribed to the formation of hydrogen bonding between
GlcNH2 as hydrogen bonding donor and the CH3COOꢀ anion as hydrogen bonding
acceptor, whereas very little change in the chemical shifts was observed for the peaks
4

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of methylene and methine in the GlcNH2 backbone.8,29 Previously, an “electrophile
nucleophile dual activation” function of the ILs for catalysis through hydrogen
bonding interactions has been proposed.32 Thus, [C2C1Im][OAc] could potentially
provide bifunctional catalytic properties due to its specific structure, which can accept
a proton and donate a proton at the same time via intermolecular hydrogen bonding
interactions.18 It is therefore believed that both the cation and anion of the
[C2C1Im][OAc] play a synergistical role in activation of the substrate during the
catalysis. The specific binding interactions between GlcNH2 and [C2C1Im][OAc] were
considered as a possible intermediate state for further isomerization in the
condensation reactions leading to DOF and FZ.
Molar ratio of
[C C Im][OAc]/GlcNH
2
1
2
6:1
2:1
1:1
0.5:1
0:1
10
9
8
7
6
5
4
3
2
δ / ppm
1
Fig. 1 The effect of molar ratios of [C2C1Im][OAc]/GlcNH2 on the H NMR spectra
for GlcNH2 in DMSOꢀd6 solution (the chemical shift scale is in units of δ).
This assumption was further supported by the mutarotation behavior of the substrate.
HClꢀfree GlcNH2, when dissolved in the DMSOꢀd6, was predominantly an αꢀanomer
in the pyranose form (Fig. S1ꢀS2, ESI†). Keeping the sample at room temperature for
3 days for equilibrium, the mutarotation between the αꢀ and βꢀanomers of GlcNH2 in
1
DMSOꢀd6 solution is still negligible according to the H and 13C NMR spectra (Fig.
S7ꢀS8, ESI†). However, in the presence of catalytic amounts of [C2C1Im][OAc],
5

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mutarotation to the equilibrium mixtures occurred rapidly (Fig. S9, ESI†). Besides,
the relative intensity of peaks belonging to the βꢀanomer increased at the expense of
the αꢀanomer when increasing the molar ratio of [C2C1Im][OAc]/GlcNH2 (Fig. 2). An
enlarged format of the area (δ = 50~100 ppm) highlighted by the dashed line was
shown in the supporting information (Fig. S10, ESI†). As discussed above,
specifically cooperative hydrogen bonding interactions presumably favor activation of
the GlcNH2, hence facilitating the interconversion of the αꢀ and βꢀanomers.
GlcNH
2
αꢀC1
β/α
βꢀC1
87.72%
82.64%
76.92%
60.60%
25.45%
22.67%
0%
180 160 140 120 100 80
δ / ppm
60
40
20
Fig. 2 The changes of β/α anomeric composition of GlcNH2 calculated according to
1
the integral area of βꢀH1/αꢀH2 in the H NMR spectra (the chemical shift scale is in
units of δ and molar ratio of [C2C1Im][OAc]/GlcNH2 = 0:1, 0.1:1, 0.2:1, 0.5:1, 0.6:1,
0.9:1, 1:1 from below to top).
Compared with the imidazolium cations bearing weaker hydrogen bonding acceptors,
the ILs anions, displaying highest hydrogen bonding basicity, tend to form strong
hydrogen bonding interactions with the substrate.19 Therefore, the obtained results
may support a hypothesis that the basic CH3COOꢀ anion could promote the proton
transfer and further facilitate mutarotation of GlcNH2 in such catalytic system.16,19
The relatively small CH3COOꢀ anion, as good hydrogen bonding acceptor and
exhibiting great capability of forming hydrogen bonding, favors attacking hydrogen
6

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atoms of the more activated anomeric hydroxyl, thus leading to mutarotation. GlcNH2
is usually in the pyranose forms, however, its conversion to DOF and FZ is proposed
to proceed via the straightꢀchain form.13,34 It was shown that simple aldehydes can be
converted through the CH3COOꢀ anion within the ILs according to the pathway
depicted in Fig. 3, giving a semiacetalꢀtype structure. Consequently, it is reasonable to
deduce that GlcNH2ꢀ[C2C1Im][OAc] coordination via hydrogen bonding is promoting
the formation of the acyclic form for GlcNH2 and facilitating the activation of
nitrogen electron pair as a nucleophile, which then undergo further intermolecular
nucleophilic cyclization and dehydration to produce the sixꢀmembered heterocycle
pyrazine derivatives, called DOF and FZ. In summary, these results clearly indicate
that the hydrogen bonding is formed between the hydroxyls and amino of GlcNH2 and
[C2C1Im][OAc].
Fig. 3 Proposed [C2C1Im][OAc] interaction with GlcNH2 in DMSO. Acetate anion
catalyze the mutarotation leading to interconversion of αꢀ and βꢀpyranose anomers.
Furthermore, the formation of hydrogen bonding between GlcNH2 and [C2C1Im][OAc]
is expected to affect carbon atoms around the the hydroxyls and amino groups.
7

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Therefore, the 13C NMR chemical shifts difference (ꢁδ) values of the GlcNH2 were
employed to further support the aboveꢀmentioned suggestion. It was concluded from
NMR spectra, in particular from 13C NMR experiments, the CH3COOꢀ anion, is much
more involved in the interaction with the more acidic hemiacetal hydroxyl group in
GlcNH2 (C1ꢀOH), which promote the ring opening and subsequent nucleophilic
addition to give the products. The 13C NMR chemical shifts and chemical shift
difference (ꢁδ) values for the above different cases are listed in Table S1 according to
the numbering marked in Scheme 1. As the molar ratio of [C2C1Im][OAc]/GlcNH2
increased, both the peaks of αꢀC1 and βꢀC1 markedly shift downfield compared with
other carbons (indicated by the lightꢀblue frame in Table S1). [C2C1Im][OAc] might
also interact with other accessible hydrogen atoms of the GlcNH2 such as the
hydroxyl groups at αꢀC4 or βꢀC3, leading to downfield shifts. These positions are,
however, not directly involved in the condensation steps (Fig. 4).29 Generally, DOF
and FZ are obviously formed through an intermolecular nucleophilic addition reaction
involving the activated carbonyl carbon (C1) and nitrogen electron pair as a
nucleophile.13 Thus, the observed obvious changes in the 13C chemical shift of
GlcNH2 could confirm the specific coordination interactions between C1ꢀOH of the
GlcNH2 and CH3COOꢀ anion, and further explain the nucleophilic activation of
GlcNH2 by hydrogen bonding interactions. Activation of the nucleophile by
CH3COOꢀ anion through hydrogen bonding interactions during the catalysis has
earlier been proposed.32 It was therefore stated that the pronounced catalytic
performance originated from an explicit hydrogen bond interactions between
protonꢀacceptor sites of [C2C1Im][OAc] anion and protonꢀdonor hydroxyl and amino
groups of the GlcNH2 in catalyzing DOF and FZ formation. In addition, to guarantee
a completely homogeneous synthesis pathway, the addition of solvent like DMSO is
necessary. Our experimental results showed that addition of DMSO as solvent was
weakly coordinating and could facilitate the solvation between GlcNH2 and
[C2C1Im][OAc] without impairing the performance of the [C2C1Im][OAc].40,41
8

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3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
5.5
αꢀC1
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
βꢀC1
βꢀC5
αꢀC2
αꢀC4
βꢀC3
αꢀC6
αꢀC3
αꢀC5
βꢀC2
βꢀC6
βꢀC4
0
1
2
3
4
5
6
7
0
1
2
3
4
5
6
7
[C
C Im][OAc]/GlcNH (molar ratio)
2
1
[C C Im][OAc]/GlcNH (molar ratio)
2
2
2
1
Fig. 4 Trend of the chemical shift difference of carbons in 13C NMR of GlcNH2 (αꢀ
and βꢀanomers) with increasing [C2C1Im][OAc] concentration (ꢁδ=δobs−δ0, the
chemical shift scale is in units of δ).
The above results clearly confirmed that hydrogen bonding is formed between
GlcNH2 and [C2C1Im][OAc], supporting the existence of intermolecular contacts and
the bifunctional activation of GlcNH2. However, the interaction sites of
[C2C1Im][OAc] during catalysis still remain unknown. Thus, the effect of GlcNH2
1
concentration on the H and 13C chemical shifts of [C2C1Im][OAc] was investigated
1
as well to elucidate the interaction sites on the ILs during catalysis. The H and 13C
NMR chemical shifts and ꢁδ values for the above different cases are listed in Table S2
and S3. For the chemical shifts of the protons in the imidazolium ring, it was observed
that the chemical shift of H2 is more sensitive to the addition of GlcNH2, showing a
marked upfield shift (indicated by the lightꢀgreen frame in Table S2).28ꢀ31,42 However,
negligible changes were observed in methyl and ethyl protons of the cation and anion
as the concentration of GlcNH2 increased (Fig. 5a). The possible explanation is that
relatively weak intermolecular hydrogen bonding was formed between oxygen or
nitrogen atoms of GlcNH2 and the most acidic H2 in the imidazolium ring while
disrupting the interionic hydrogen bonding network in ILs, leading to an upfield
shift.19,29 Moreover, 13C chemical shifts of [C2C1Im][OAc] have been investigated as
well and the results were shown in Fig. 5b. The carbonyl (C=O) of the CH3COOꢀ
anion moved downfield significantly, indicating that the strong hydrogen bonding was
formed between CH3COOꢀ anions and hydroxyl and amino groups of GlcNH2.28,29 In
addition, the peaks of C2 showed a pronounced upfield change, while negligible
9

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changes were observed for the other carbon atoms on the cation as the concentration
of GlcNH2 increased, further indicating weaker hydrogen bonding between the most
acidic H2 of the imidazolium cation and GlcNH2 was formed leading to upfield
change of C2. More interestingly, a significant decrease in the value of the chemical
shift of C9 (CH3COOꢀ) was also found (indicated by the lightꢀred frame in Table S3).
This clearly indicates strong hydrogen bond interactions between the carboxyl and
hydroxyl and amino groups were formed, which led to the increase of electron density
around the C9 nucleus and thus a upfield shift of its 13C NMR signal. A similar
phenomenon of ILs has also been observed by Zhang et al. for cellulose dissolved in
1
[C2C1Im][OAc].29 Both H and 13C NMR spectra confirmed that the catalytic
efficiency of the [C2C1Im][OAc] it does not solely due to the CH3COOꢀ anions, and
the imidazolium cation also play a key role in the molecular interactions during
catalysis. For GlcNH2 conversion, therefore, [C2C1Im][OAc] was favored.
b)
a)
0.5
0.4
2.5
2.0
C10
C2
C4
C5
C7
C6
C9
C8
H2
H5
H4
H7
H6
H9
H5
0.3
1.5
0.2
1.0
0.1
0.5
0.0
0.0
ꢀ0.1
ꢀ0.2
ꢀ0.3
ꢀ0.4
ꢀ0.5
ꢀ0.5
ꢀ1.0
ꢀ1.5
ꢀ2.0
ꢀ2.5
0.1
0.2
0.3
[OAc] (molar ratio)
2 1
0.4
0.5
0.1
0.2
0.3
0.4
0.5
GlcNH / C C Im
][OAc] (molar ratio)
2 [
2 1
GlcNH C C Im
/
]
2 [
Fig. 5 Changes of proton (a) and carbon (b) chemical shift difference in
[C2C1Im][OAc] with increasing GlcNH2 in DMSOꢀd6 (ꢁδ = ꢁδobs ꢀ ꢁδpure, the
chemical shift scale is in units of δ).
The findings clearly indicated that hydrogen bonding is formed between GlcNH2 and
[C2C1Im][OAc], and this can account for the enhanced reactivities observed.
1
Therefore, Hꢀ1H homonuclear NOE spectra were recorded in order to provide
straightforward and complementary information about these interactions.28,36 As
depicted in Fig. S11, a close contact can be visualized between the overlapped peak of
GlcNH2 hydroxyl and amino protons and the CH3COOꢀ anions. Besides, a cross peak
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between H2 imidazolium ring proton and the active hydrogen groups of the GlcNH2
was also found. Hydrogen bonding interactions, therefore, do exist between GlcNH2
and [C2C1Im][OAc] during catalysis process and this is probably the main driving
force for the catalysis. As expected, variations in spinꢀlattice relaxation time (T1) can
provide information about the dynamics of ILs and present quantitative data regarding
1
their interactions with the solute.17 Thus, spinꢀlattice relaxation time of the H nuclei
of [C2C1Im][OAc] was therefore studied. As presented in Table 1, there were only
slight variations in the relaxation time of the protons in the cations of the
[C2C1Im][OAc] as a function of the GlcNH2 content. Conversely, the relaxation
parameters of the CH3COOꢀ anion (H9) were strongly influenced by the presence of
GlcNH2 (see the lightꢀpurple frame in Table 1). The change in the longitudinal
relaxation time of the CH3COOꢀ anion with the increasing GlcNH2 concentration was
vastly larger than those expected due to the variation of the solution viscosity alone.
The T1 value of the CH3COOꢀ anion (H9), on the other hand, decreased drastically.
This agreed with the conclusions presented earlier, and provided further evidence
regarding the formation of hydrogen bonding between the CH3COOꢀ anions and the
carbohydrate hydroxyl and amino groups.17,43
Table 1. SpinꢀLattice Relaxation Time T1 (s) of the corresponding protons of the
[C2C1Im][OAc] in the neat ILs (0:1) and the carbohydrate/IL solutions (molar ratio =
1:1 and 2:1)
Hꢀ2
Hꢀ5
Hꢀ4
Hꢀ7
Hꢀ6
Hꢀ9
Hꢀ8
0:1
1:1
2:1
1.169
1.337
1.306
3.010
3.317
2.638
3.064
3.340
2.700
1.337
1.347
1.123
1.473
1.443
1.175
2.933
1.881
1.643
1.916
1.990
1.682
Based on the above results, both 1D and 2D NMR spectra clearly confirmed that
hydrogen bonding is the main driving force for the GlcNH2 catalytic conversion in
[C2C1Im][OAc]. Therefore, if all the hydroxyls and amino of GlcNH2 were acetylated,
there would be no chance for the formation of hydrogen bonding between the
substrate and [C2C1Im][OAc]. To verify the conclusion stated above, analogous
measurements were carried out on solutions of
Dꢀglucosamine pentaacetate, a
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molecule lacking hydrogen bond donors comparable to that of GlcNH2. As expected,
there was only a minor variation in the signals of ꢀglucosamine pentaacetate in the
presence of [C2C1Im][OAc] both in the H and C NMR spectra, presumably due to
the inability of ꢀglucosamine pentaacetate as an inferior hydrogen bonding donor to
D
1
13
D
form intermediate state for further dehydration (Fig. 6).17,29 Thus, an “electrophile
nucleophile dual activation” process of [C2C1Im][OAc] for catalysis through
hydrogen bonding interactions cannot proceed. Actually, experimental results further
prove our conjecture, showing that no products were formed even at high temperature
(80 °C) for 2 hours (Fig. S12, ESI†). Therefore, in contrast to
Dꢀglucosamine
pentaacetate, GlcNH2, as better hydrogen bonding donor, tend to form strong
interactions with [C2C1Im][OAc], i.e. hydrogen bonding is a major driving force for
the catalytic conversion of GlcNH2 in [C2C1Im][OAc].
(a)
(b)
8 h
10 h
2 h
5 h
2ꢀ4 min
2ꢀ4 min
pure sample
pure sample
200 180 160 140 120 100 80 60 40 20
δ / ppm
0
10
9
8
7
6
5
4
3
2
1
0
δ / ppm
Fig. 6 Effect of [C2C1Im][OAc] on the signal changes of glucosamine pentaacetate
1
both in the H (a) and 13C NMR (b) spectra (the chemical shift scale is in units of δ
and molar ratio of [C2C1Im][OAc]/glucosamine pentaacetate = 0.5:1).
Although the importance of hydrogen bonding was justified by aboveꢀmentioned
experiments, it is not known if this catalytic mechanism would really work in the real
system. To understand the catalytic mechanism in the real system, an in situ NMR
study with GlcNH2 as substrate and [C2C1Im][OAc] as catalyst was carried out in
DMSOꢀd6 at 60 °C (Fig. 7). As it can be seen the peaks of hydroxyl and amino
protons of GlcNH2 overlapped each other and changed into one unresolved broad
peak. The overlapped peaks gradually shifted upfield since hydrogen bonding will be
12

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broken as temperature increased, which were in accordance with previous
1
research.17,29 Moreover, our H NMR studies shows that the ratio between the
anomers changes significantly. Thus, these behaviors were similar to the results
observed at ambient temperature and directly indicated that relatively strong hydrogen
bonding interactions indeed exist even at higher temperature. Additionally, when
increasing the reaction temperature and time, DOF and FZ were gradually formed
(indicated by the lightꢀgreen frame in Fig. 7).44ꢀ46
136 min
67 min
17 min
5 min
2 min
9
8
7
6
5
4
3
2
1
δ
/ ppm
Fig. 7 The timeꢀprogression stack of in situ 1H NMR spectra of GlcNH2 catalyzed by
[C2C1Im][OAc] in DMSOꢀd6 solution at 60 °C (the chemical shift scale is in units of
δ).
Based on above NMR spectral study, a plausible reaction pathway was proposed in
order to elucidate the catalysis process for the formation of the two pyrazine
derivatives with this specific [C2C1Im][OAc]. The surprising finding was that the
mechanism of catalysis highlighted the importance of not only the electrophilic
nucleophilic dual activation through hydrogen bonding interactions but also activation
of the nitrogen lone pair electrons by [C2C1Im][OAc], facilitating further nucleophilic
addition reactions and leading to the formation of DOF and FZ. Studies on interaction
sites of [C2C1Im][OAc] by 13C NMR have found that the carbonyl (C=O) of the
CH3COOꢀ anion moved downfield significantly. CH3COOꢀ anion, therefore, was
proposed to interact with hydrogen atoms of the more activated anomeric hydroxyl of
the sugar to give a complex, which increases the concentration of the open chain
13
aldose form of the sugar.13,34 In addition, based on the shift changes in C NMR, as
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the molar ratio of [C2C1Im][OAc]/GlcNH2 increased, both the peaks of αꢀC1 and
βꢀC1 markedly shift downfield compared with other carbons, clearly demonstrating
that the specific interaction between the more acidic hemiacetal hydroxyl group in
GlcNH2 (C1ꢀOH) and the CH3COOꢀ anion, thus facilitating the formation of open
chain aldose form of the amino sugars. Next, intermolecular nucleophilic addition
involving the activated carbonyl carbon (C1) and nitrogen electron pair as a
nucleophile affords the sixꢀmembered heterocycle, an intermediate typically called
dihydropyrazine (Schiff Bases), in which an dehydrogenation (oxidative) process
leading to FZ – this process is facilitated by the presence of hydrogen peroxide and
simultaneously a dehydration and isomerization (electrolytic rearrangement) to give
DOF.13,45,47 Interestingly, activation of nitrogen electron pair by [C2C1Im][OAc] is
also a key factor determining the formation of pyrazine derivatives due to
condensation reaction involving the aldehyde and nitrogen electron pair acts as a
nucleophile. For comparison and to provide evidence for the nucleophilicity of
aminoꢀnitrogen, the reaction of GlcNAc was studied under similar conditions.
GlcNAc as the starting material, 0% yield of DOF and FZ was obtained in the
presence of catalytic amounts of [C2C1Im][OAc] at relatively high temperature (Fig.
S13, ESI†). This result was surprising given the high catalytic activity of
[C2C1Im][OAc] in the dehydration of GlcNH2. This difference may be due to the
presence of basic nitrogen electron pair within GlcNH2 and its absence in GlcNAc. In
recent literatures, GlcNAc was known to yield 3ꢀacetamidoꢀ5ꢀacetylfuran, in which
nucleophilic attack by a hydroxyl group affords the five membered heterocycle,
presumably due to the single acetylation of amino group in the GlcNAc, decreasing
the nucleophilic activities of nitrogen atom and thus inhibiting the nucleophilic
addition.5,6,9 Thus, amino group containing an active lone pair of electrons on the
electronegative nitrogen atom favors the nucleophilic addition process. Therefore, it is
indicating that the CH3COOꢀ anion enhanced nucleophilic ability of the nitrogen
electron pair and the imidazolium cation improved the electrophilic ability of the
aldehyde by forming intermolecular hydrogen bonds, which were the main driving
force for this catalytic reaction. The proposed reaction mechanism was presented in
Scheme 2. Although, some clues concerning the mechanism have been obtained, more
detailed studies are currently underway in our research group.
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OH
H
H
O
HO
H
H
H
NH2
OH
OH
OH
OH
OH
H
H
H
ꢀpyranose
O
H
OH
OH
HO
CH2CH3
CH3COO
H3
C
HO
N
H
N
H
Proton Transfer
O
H
Promoter IL
O
O
NH2
H
HO
HO
NH2
O
CH3
OH
O
H
OH
NH2
1ꢀEthylꢀ3ꢀmethylimidazolium Acetate
Openꢀchain Forms
Coordination via Hydrogen Bonding
2ꢀAminoꢀ2ꢀdeoxyꢀDꢀglucose
OH
H
H
O
HO
OH OH
H
OH
H
N
N
OH
NH2
OH OH
OH
H
OH
ꢀpyranose
OH OH
Fructosazine (FZ)
CH2OH
HO
HO
H
H
H
OH
OH
OH
OH
OH
H
N
N
H2
N
OH
OH
N
OH
OH
O
Intermolecular
Nucleophilic Addition
H
H
H
OH
OH
O
OH
OH
H
HO
H
NH2
H
OH
OH
CH2OH
Path Two
N
OH
OH
OH
OH
ꢀ2H2O
Activation by
Basic ILs
H
IntermediateꢀꢀꢀDihydropyrazine
H
OH
OH
OH
N
N
OH
OH OH
N
OH
OH
OH
Isomerization
OH
OH
OH OH
N
Electrolytic
Rearrangement
OH
OH
Deoxyfructosazine (DOF)
ꢀH2O
Scheme 2. Proposed reaction pathways for the formation of fructosazine (path one in
red) and deoxyfructosazine (path two in blue) from GlcNH2.
To explore the kinetic behavior of the selfꢀcondensation of GlcNH2, investigation on a
variety of reaction parameters was performed in the real system. In the blank
experiment, i.e. in the absence of [C2C1Im][OAc], no products were detected at 80 °C
with different reaction times (Fig. S14, ESI†), confirming that DMSO is inactive for
the production of DOF and FZ, which was in accordance with the mechanistic studies
above.40,41 The presence of catalytic amounts of [C2C1Im][OAc] could efficiently
catalyze the condensation reaction of GlcNH2 to obtain the DOF and FZ, which were
qualitatively identified by 1H NMR, 13C NMR, 1Hꢀ1H COSY, and HSQC spectra (Fig.
S15ꢀS18, ESI†). As evident by Fig. 8, significant effects of reaction temperature and
time on the substrate conversion (with black curves) and yields of products (with blue
curves) were observed. As increasing the temperature from 60 to 100 °C, both
substrate conversion (indicated by black arrow) and product yields (indicated by blue
arrow) clearly enhanced. The yields of DOF and FZ, and GlcNH2 conversion were
1
quantitatively calculated by H NMR spectroscopy using pyrazine as an internal
standard.48 The maximum yields of products were 37%, which was achieved at
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100 °C after a reaction time of 90 min (Fig. 8). Isolated yields of the DOF and FZ
were provided in Figure S19. In addition, an ESIꢀMS spectrum showed that there
were mainly two molecular cations (M+H)+ at m/z 305.15 and 321.15 g/mol,
respectively, corresponding to [M (DOF) + H]+ and [M (FZ) + H]+ (Fig. S20, ESI†).
On the other hand, a rapid darkening of the reaction solution from light yellow to
brown was observed, when the reaction time was increased from 5 to 120 min (Fig.
S21, ESI†). Soluble polymers were presumably formed during the reaction though it
is difficult to confirm this by NMR spectroscopy. Typically, the condensation of
GlcNH2 to DOF and FZ is a complex multistep process with many possible pathways
and side reactions.49,50
40
100
35
90
80
70
60
50
40
30
20
10
0
30
25
20
15
10
5
Conversion (60
Conversion (80
Conversion (100
)
)
)
Yields (60
Yields (80
Yields (100
)
)
)
0
120
90
5
10
30
60
20
Time / min
Fig. 8 GlcNH2 conversion and product yields at different reaction time and
temperature.
Conclusions
In summary, the detailed catalytic mechanism of [C2C1Im][OAc] was elucidated via
the investigation of the hydrogen bonding interactions between [C2C1Im][OAc] and
GlcNH2 using NMR techniques. The CH3COOꢀ anion was identified as the primary
catalyst, while the cations of [C2C1Im][OAc] worked synergistically to form hydrogen
bonds, thus activating the substrate and facilitating the homogeneous baseꢀcatalyzed
reaction. Our NMR data clearly demonstrated that the hydrogen bonding was formed
between GlcNH2 and [C2C1Im][OAc], and suggest that this is the major driving force
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for the catalytic reactions. [C2C1Im][OAc], presented fascinating catalytic
performance, could efficiently convert GlcNH2 into DOF and FZ with high yields and
selectivity. Based on NMR studies, a plausible reaction pathway was proposed.
Consequently, understanding the catalytic nature of ILs will open up a new avenue for
selective transformation of nonꢀedible biomass into high valueꢀadded chemicals with
potential industrial applications.
Experimental details
1.1 Materials
Practical grade Dꢀglucosamine hydrochloride (designated as GlcNH2·HCl, white
crystalline powder) was obtained from GoldenꢀShell Biochemical Co. Ltd. HClꢀfree
Dꢀglucosamine sample was prepared by stirring with triethylamine and
dichloromethane for 2ꢀ3 days until without crystalline solid. After stirring, samples
were extracted by dichloromethane for 4ꢀ5 times to remove triethylamine
hydrochloride as much as possible. [C2C1Im][OAc] was purchased from Shanghai
Cheng Jie Chemical Co. Ltd. DMSOꢀd6 (99.9%, atom D) was supplied by Qingdao
Teng long Microwave Technology Co. Ltd. Deuterium oxide (D2O, 99.9% atom D)
was supplied by Cambridge Isotope Laboratory. Dimethylsulfoxide (DMSO),
pyrazine (internal standard) and all other chemicals (analytical grade) were purchased
from Sinopharm Chemical Reagent Co. Ltd. All reagents were used without further
purification.
1.2 General reaction procedures
The condensation reaction of GlcNH2 was carried out in a round bottom flask that
was heated in the oilꢀbath in the range from 60 °C to 100 °C with a continuous
magnetic stirring and a condenser. Typically, 179.2 mg GlcNH2 was added into
desired 170.2 mg [C2C1Im][OAc] (molar ratio 1:1) followed by the addition of 2 ml
coꢀsolvent of dimethylsulfoxide (DMSO). The reaction was vigorously stirred until a
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transparent solution was formed. At different time intervals, 0.1 ml samples were
taken, and quenched immediately with ice water bath for further analysis. For
comparison, similar procedures were followed for GlcNH2 condensation in pure
DMSO in the absence of the [C2C1Im][OAc] catalyst. Besides, similar reaction
procedure was performed for NꢀacetylꢀDꢀglucosamine (GlcNAc) and Dꢀglucosamine
pentaacetate as substrate at high temperature, respectively. The yields of DOF and FZ,
as well as the GlcNH2 conversion during the reaction, were quantitatively analyzed by
1H NMR spectroscopy using pyrazine as internal standard substance. Pyrazine with
concentration of 0.3 mg/ml in D2O as standard solution was prepared and 0.1 ml of
1
reaction mixture was mixed with 0.4 ml this standard solution to give the H NMR
sample. DOF and FZ yields were calculated as:
ꢀꢁꢂꢃꢄ ꢁꢅ ꢆꢇꢁꢈꢉꢊꢋꢄ
Yield = 2 ×
× 100%
ꢀꢁꢂꢃꢄ ꢁꢅ ꢄꢉꢌꢄꢋꢇꢍꢋꢃꢄ
1.3 NMR sample preparation
For observing the changes in 13C chemical shifts of GlcNH2 with increasing
[C2C1Im][OAc] concentrations, samples were prepared by adding different amounts
of [C2C1Im][OAc] into solutions of 0.5 ml DMSOꢀd6 and 20 mg GlcNH2. Ultrasonic
treatment of the samples was applied to ensure complete dissolution of the substrates
in the ILs prior to NMR analysis. Similarly, to analyze the effect of GlcNH2
concentration on the proton and carbon chemical shifts of [C2C1Im][OAc], samples
were prepared by adding different weights of GlcNH2 into the solution of 0.5 ml
DMSOꢀd6 and 20 mg [C2C1Im][OAc] with constant stirring (GlcNH2 : [C2C1Im][OAc]
mass ratio: 0, 10, 20, 30, 50 wt%). Upon complete dissolution, samples were quickly
transferred into 5 mm NMR tubes and measured by NMR. For comparison, samples
were prepared by adding certain amounts of [C2C1Im][OAc] into the solution 20 mg
Dꢀglucosamine pentaacetate and GlcNAc in 0.5 ml DMOSꢀd6, respectively (the molar
ratio of [C2C1Im][OAc]/glucosamine pentaacetate or GlcNAc = 0.5:1). Procedures for
samples preparation were also used to acquire 1H−1H NOESY spectra.
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1.4 In situ NMR sample preparation
Samples were prepared by adding 179 mg GlcNH2 into desired 85 mg
[C2C1Im][OAc] (the molar ratio of GlcNH2/[C2C1Im][OAc] = 2:1) followed by the
addition of 0.5 ml DMSOꢀd6, which provided a fieldꢀfrequency lock and NMR
internal standards. After complete dissolution, the samples were transferred into 5 mm
NMR tube. When the temperature inside the NMR spectrometer probe was stabilized
1
at 60 °C, the tube was immediately transferred to the NMR spectrometer. In situ H
NMR spectra were recorded at certain times during the experiment.
1.5 Characterization
The 1D and 2D NMR spectra were acquired on a Bruker AVꢀIII 400 MHz NMR
1
spectrometer (9.39 T) equipped with auto sampler. H and 13C NMR spectra were
1
13
obtained at frequencies of 400.13 and 100.61 MHz, respectively. H and C NMR
titration experiments were operated at room temperature with 16 scans and 500 scans,
1
respectively. In situ H NMR experiments were performed at 353 K. NOESY NMR
experiments were carried out using standard library sequences with mixing times, τm,
of 500 ms at room temperature. All spectra were acquired using DMSOꢀd6 for
fieldꢀfrequency lock. Spinꢀlattice relaxation time (T1) measurement of the
[C2C1Im][OAc] protons was carried out at 298 K. The T1 values were measured by
the inversion recovery pulse program (t1ir). Relaxation measurements were carried
out with relaxation delays at least five times T1 and the instrument was carefully
tuned, shimmed, and the 90 degree pulse calibrated before each measurement. The
products were further qualitatively identified by the positiveꢀion ESI mass spectrum
on a Bruker MicroTOFꢀQ III.
Acknowledgements
The authors would like to acknowledge the financial support from the Major State
Basic Research Development Program of China (973 Program) (No. 2012CB215305)
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and Natural Science Foundation of China (No. 21106172, 21403273). Yan Qiao
thanks the Chinese Academy of Sciences (2013YC002) and the Youth Innovation
Promotion Association of Chinese Academy of Sciences (2011137) for financial
support. Christian Marcus Pedersen acknowledges the CAS President’s International
Fellowship Initiative (2015VMB052). Special thanks are given to Jennifer Hongyang
Zhang and Jun Ren for their assistance during revision.
Notes and references
1 A. Corma, S. Iborra and A. Velty, Chem. Rev., 2007, 107, 2411ꢀ2502.
2 M. J. Climent, A. Corma and S. Iborra, Green Chem., 2014, 16, 516ꢀ547.
3 L. Xu, Y. Jiang, Q. Yao, Z. Han, Y. Zhang, Y. Fu, Q. Guo and G. W. Huber, Green
Chem., 2014, 17, 1281ꢀ1290.
4 T. Deng, X. Cui, Y. Qi, Y. Wang, X. Hou and Y. Zhu, Chem. Commun., 2012, 48
,
5494ꢀ5496.
5 X. Chen, S. L. Chew, F. M. Kerton and N. Yan, Green Chem., 2014, 16, 2204ꢀ2212.
6 K. W. Omari, L. Dodot and F. M. Kerton, ChemSusChem, 2012, , 1767ꢀ1772.
5
7 Y. Wang, C. M. Pedersen, T. Deng, Y. Qiao and X. Hou, Bioresour. Technol., 2013,
143, 384ꢀ390.
8 Q. Chen, A. Xu, Z. Li, J. Wang and S. Zhang, Green Chem., 2011, 13, 3446ꢀ3452.
9 F. M. Kerton, Y. Liu; K. W. Omari, K. Hawboldt, Green Chem. 2013, 15, 860ꢀ871.
10 M. W. Drover, K. W. Omari, J. N. Murphy and F. M. Kerton, RSC Adv., 2012, 2,
4642ꢀ4644.
11 Y. Ohmi, S. Nishimura and K. Ebitani, ChemSusChem, 2013,
6, 2259ꢀ2262.
12 C. K. S. Pillai, W. Paul and C. P. Sharma, Prog Polym Sci., 2009, 34, 641ꢀ678.
13 L. Jia, Y. Wang, Y. Qiao, Y. Qi and X. Hou, RSC Adv., 2014,
14 R. Sheldon, Chem. Commun., 2001, 2399ꢀ2407.
4, 44253ꢀ44260.
15 H. OlivierꢀBourbigou, L. Magna and D. Morvan, Appl Catal A-Gen., 2010, 373
,
1ꢀ56.
20

Page 21 of 23
Physical Chemistry Chemical Physics
View Article Online
DOI: 10.1039/C5CP02169C
16 N. R. Dhumal, H. J. Kim and J. Kiefer, J. Phys. Chem. A., 2009, 113
,
10397ꢀ10404.
17 R. C. Remsing, R. P. Swatloski, R. D. Rogers and G. Moyna, Chem. Commun.,
2006, 1271ꢀ1273.
18 T. Liebert and T. Heinze, BioResources, 2008, 3, 576ꢀ601.
19 M. Brehm, H. Weber, A. S. Pensado, A. Stark and B. Kirchner, Phys. Chem. Chem.
Phys., 2012, 14, 5030ꢀ5044.
20 M. E, Zakrzewska, E. Bogelꢀyukasik, R, Bogelꢀyukasik. Energy Fuels 2010, 24
,
737ꢀ745.
21 T. Welton, Coord. Chem. Rev., 2004, 248, 2459ꢀ2477.
22 A. C. Cole, J. L. Jensen, I. Ntai, K. L. T. Tran, K. J. Weaver, D. C. Forbes and J. H.
Davis, Jr, J. Am. Chem. Soc., 2002, 124, 5962ꢀ5963.
23 A. S. Amarasekara, M. A. Hasan. Tetrahedron Lett., 2014, 55, 3319ꢀ3321.
24 A. S. Amarasekara, A. Razzaq. Carbohydr. Res., 2014, 386, 86ꢀ91.
25 J. Viell and W. Marquardt, Appl. Spectrosc., 2012, 66, 208ꢀ217.
26 J. Kiefer, K. Obert, A. Bosmann, T. Seeger, P. Wasserscheid and A. Leipertz,
Chemphyschem., 2008, 9, 1317ꢀ1322.
27 M. Thomas, M. Brehm, O. Holloczki, Z. Kelemen, L. Nyulaszi, T. Pasinszki and
B. Kirchner, J Chem Phys, 2014, 141, 024510.
28 J. M. M. Araujo, A. B. Pereiro, J. N. Canongia Lopes, L. P. Rebelo and I. M.
Marrucho, J. Phys. chem. B., 2013, 117, 4109ꢀ4120.
29 J. Zhang, H. Zhang, J. Wu, J. Zhang, J. He and and J. Xiang, Phys. Chem. Chem.
Phys., 2010, 12, 1941ꢀ1947.
30 M. E. Ries, A. Radhi, A. S. Keating, O. Parker and T. Budtova,
Biomacromolecules, 2014, 15, 609ꢀ617.
31 P. A. Hunt, C. R. Ashworth and R. P. Matthews, Chem. Soc. Rev., 2015, 44
,
1257ꢀ1288.
21

Physical Chemistry Chemical Physics
Page 22 of 23
View Article Online
DOI: 10.1039/C5CP02169C
32 A. K. Chakraborti and R. S. Roy, J. Am. Chem. Soc., 2009, 131, 6902ꢀ6903.
33 A. R. Hajipour and F. Rafiee, J. Iran. Chem. Soc., 2009, 6, 647ꢀ678.
34 E. A. Khokhlova, V. V. Kachala, V. P. Ananikov. ChemSusChem 2012,
5,
783ꢀ789.
35 A. Pinkert, K. N. Marsh, S. S. Pang and M. P. Staiger, Chem. Rev., 2009, 109
6712ꢀ6728.
,
36 V. P. Ananikov, Chem. Rev., 2011, 111, 418ꢀ454.
37 D. Horton, J. S. Jewell, K. D. Philips, J. Org. Chem., 1966, 31, 4022ꢀ4025.
38 X. Sun, Q. Tian, Z. Xue, Y. Zhang and T. Mu, RSC Adv. 2014, 4, 30282ꢀ30291.
39 H. B. Zhao, J. E. Holladay, H. Brown and Z. C. Zhang, Science, 2007, 316
,
1597ꢀ1600.
40 J. M. Andanson, E. Bordes, J. Devémy, F. Leroux, A. A. H. Pádua and M. F. C.
Gomes, Green Chem., 2014, 16, 2528ꢀ2538.
41 R. C. Remsing, Z. W. Liu, I. Sergeyev and G. Moyna, J. Phys.Chem. B, 2008, 112
,
7363ꢀ7369.
42 C. S. Lovell, A. Walker, R. A. Damion, A. Radhi, S. F. Tanner, T. Budtova and M.
E. Ries, Biomacromolecules, 2010, 11, 2927ꢀ2935.
43 N. AssaꢀMunt, J. Granot, R. W. Behling and D. R. Kearns, Biochemistry 1984, 23
,
944ꢀ955.
44 J. Rohovec, J. Kotek, J. A. Peters and T. Maschmeyer, Eur. J. Org. Chem., 2001,
2001, 3899ꢀ3901.
45 K. Sumoto, M. Irie, N. Mibu, S. Miyano, Y. Nakashima K. Watanabe and T.
Yamaguchi, Chem. Pharm. Bull., 1991, 39, 792ꢀ794.
46 S. Wu, H. Fan, Q. Zhang, Y. Cheng, Q. Wang, G. Yang and B. Han, Clean-Soil
Air Water, 2011, 39, 572ꢀ576.
47 N. Kashige, T. Yamaguchi, N. Mishiro, H. Hanazono, F. Miake and K. Watanabe,
Biol. Pharm. Bull., 1995, 18, 653ꢀ658.
48 T. Rundlöf, M. Mathiasson, S. Bekiroglu, B. Hakkarainen, T. Bowden and T.
Arvidsson, J. pharmaceut. biomed., 2010, 52, 645ꢀ651.
22

Page 23 of 23
Physical Chemistry Chemical Physics
View Article Online
DOI: 10.1039/C5CP02169C
49 H. Tsuchida, Hiromichi, M. Komoto, H. Kato and M. Fujimaki, Agr. Biol. Chem.,
1973, 37, 2571ꢀ2578.
50 A. P. Zhu, J. B. Huang, A. Clark, R. Romero and H. R. Petty, Carbohydr. Res.,
2007, 342, 2745ꢀ2749.
23