Hydrolytic hydrogenation of chitin to amino sugar alcohol

Article abstract of DOI:10.1039/c7gc01063j

Chitin is the second most abundant biomass and characteristically contains nitrogen atoms in its monomer units. These favourable features promote chitin to be a potential resource for renewable organonitrogen compounds. 2-Acetamido-2-deoxysorbitol (ADS) is an attractive target in the derivatives of chitin, but the conversion of chitin to ADS has not been reported so far. In this work, we demonstrate the catalytic conversion of chitin to ADS using mechanocatalysis in the presence of H₂SO₄ and subsequent hydrolytic hydrogenation by H₂SO₄ and Ru/TiO₂ without any purification process. Our study clarified that the yield of ADS is strongly influenced by the reaction temperature and pH. The hydrolysis favourably proceeds at high temperature and low pH (2.0), but the hydrogenation needs a low temperature and a specific pH of 3-4 to achieve high selectivity. Specifically, in the hydrogenation step, an acid causes various side-reactions of amide and hemiacetal groups especially in the presence of a Ru catalyst, whereas even a small amount of base drastically accelerates the retro-aldol reaction to form erythritol and N-acetylethanolamine. Therefore, a one-pot but two-step reaction is necessary to optimise both the hydrolysis and hydrogenation steps and maximise the overall yield of ADS up to 52%.

Full text of DOI:10.1039/c7gc01063j

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Hydrolytic hydrogenation of chitin to amino sugar alcohol
Hirokazu Kobayashi*, Kota Techikawara, Atsushi Fukuoka*
Institute for Catalysis, Hokkaido University, Kita 21 Nishi 10, Kita-ku, Sapporo, Hokkaido
001-0021, Japan.
E-mail: kobayashi.hi@cat.hokudai.ac.jp (H.K.); fukuoka@cat.hokudai.ac.jp (A.F. ) Fax:
+81-11-706-9139
Abstract
Chitin is the second most abundant biomass and characteristically contains nitrogen atoms in its
monomer units. These favourable features promote chitin to be a potential resource for
renewable organonitrogen compounds. 2-Acetamido-2-deoxysorbitol (ADS) is an attractive
target in derivatives of chitin, but the conversion of chitin to ADS has not been reported so far.
In this work, we demonstrate the catalytic conversion of chitin to ADS using mechanocatalysis
in the presence of H2SO4 and subsequent hydrolytic hydrogenation by H2SO4 and Ru/TiO2
without purification process. Our study clarified that the yield of ADS is strongly influenced by
the reaction temperature and pH. The hydrolysis favourably proceeds at high temperature and
low pH (2.0), but hydrogenation needs low temperature and specific pH of 3−4 to achieve high
selectivity. Specifically, in the hydrogenation step, acid causes various side-reactions of amide
and hemiacetal groups especially in the presence of Ru catalyst, whereas even a small amount of
base drastically accelerates the retro-aldol reaction to form erythritol and N-acetylethanolamine.
Therefore, a one-pot but two-step reaction is necessary to optimise both hydrolysis and
hydrogenation steps and maximises the overall yield of ADS up to 52%.
Introduction
Chitin is the most abundant inedible biomass next to lignocellulose, and it is widely found in
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both terrestrial and marine organisms.1 Lignocellulose consists of only C, H and O, but chitin
also contains N atoms in its N-acetylglucosamine (NAG) units (Scheme 1). Thus, chitin is an
attractive feedstock for organonitrogen compounds, which are more valuable than the
counterparts derived from cellulose.2
Scheme 1. Reported typical derivatives of chitin.
The first step for utilisation of chitin is its depolymerisation to monomers.2a However,
recalcitrance of chitin3 has hampered efficient and selective production of its monomeric
compounds. A patent discloses that NAG can be synthesized by partial hydrolysis of chitin in
large excess of concentrated HCl [turnover number (TON) < 0.01], neutralisation, decolouration,
deionisation, complete hydrolysis by enzymes and isolation (32% overall yield).4 This process
results in a high price of NAG up to >100 British Pounds per kilogram. Accordingly,
chitin-based biorefinery has not yet been economically established regardless of the high
potential.1,2
Recent studies have been devoted to improve the efficiency of chitin depolymerisation and to
increase the range of products (Scheme 1). Chitin was converted to 5-(chloromethyl)furfural in
2

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45% yield in the presence of concentrated HCl and 1,2-dichloroethane.5 SnCl4 catalyst
converted chitin to levulinic acid in 11.5% yield in water.6 A combined use of AlCl3 and H3BO3
degraded chitin into 5-hydroxymethylfurfural (5-HMF) in 9.0% yield.7 Formic acid solvent
transformed ball-milled chitin into 5-(formyloxymethyl)furfural (FMF) in 35% yield.8 These
compounds are promising feedstock for producing polymers and fuels,9 but characteristic
nitrogen atoms of chitin are not contained in these compounds. Instead,
3-acetamido-5-acetylfuran (3A5AF)10 was synthesised from chitin in the presence of excess
H3BO3 and NaCl (7.5% yield),11 and the pretreatment of chitin increased the yield to 28.5%.12 A
health care agent, glucosamine sulphate, was obtained as a major product in the presence of
only 100 mM H2SO4 by a co-solvent system, water/diethylene glycol diethyl ether, which
facilitated acid-catalysed hydrolysis of both glycosidic and amide bonds.13 Alcoholysis of chitin
provides alkyl NAGs, which are expected to be stable alternatives to NAG.14 Chromogen and
pyrazine are also good candidates obtained from chitin to produce fine chemicals and
medicines.15 Recently, Yan et al. proposed a new chitin derivative, 2-acetamido-2-deoxysorbitol
(ADS).16 The amino alcohol is a potential precursor to polyamides and polyesteramides as an
analogy of valorisation of sorbitol via isosorbide.9, 17 Hydrogenolysis of ADS gives
N-acetylethanolamine, which is converted to an amide-containing polyether alcohol.18
Hydrolysis of N-acetylethanolamine gives ethanolamine, the world annual demand of which is
1.3 million tonnes for manufacturing acid-absorbers, surfactants, emulsifiers and other various
products. The presence of these potential markets shows that ADS is an attractive intermediate
in chitin-based biorefinery. However, ADS was only synthesised from pure NAG, and ADS was
not obtained from chitin previously.16
Herein, we demonstrate the first catalytic conversion of chitin to ADS (Scheme 2).
Mechanocatalytic hydrolysis was utilised to produce oligosaccharide mixture from chitin in the
first step (step 1).14b The mixture was used for the one-pot synthesis of ADS without purification
in a one-step hydrolytic hydrogenation (step 2a) and a two-step method (steps 2b, 3). Challenge
in the production of ADS and its solution is discussed.
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Scheme 2. Catalytic conversion of chitin to ADS. Steps 2b and 3ab were performed in one pot.
Yields are based on initial amount of NAG unit.
Experimental
Determination of NAG content in chitin.
Purity of the chitin sample purchased from Wako was determined by ultra violet-visible
(UV-vis) spectroscopy according to the literature,19 by which the content of NAG units was
determined to be 88 wt% (4.3 mmol gdry-chitin−1).
Mechanocatalytic hydrolysis.
Chitin (5.0 g) was dispersed in 15 mL of 0.4 M H2SO4 aq. (substrate/catalyst ratio (S/C) =
3.4 [mol-NAG unit/mol-H2SO4]). After drying in vacuo, 5.2 g of resulting powder was treated
by a planetary ball-mill (Fritsch, Pulverisette 6) at 500 rpm using alumina balls (5 mm, 100 g) in
a 250 mL of alumina pot. The milling time was 6 h with a 10 min interval after every 10 min of
milling. The temperature was increased up to 327 K by heat of milling under the condition. The
pretreated chitin sample was named Oligomer-H2SO4, the solubility of which was measured by
addition of water (100 mg/10 mL), filtration with polytetrafluoroethylene (PTFE) membrane
and weighing of the dried residue. Soluble part was analysed with a high performance liquid
chromatograph (HPLC; Prominence, Shimadzu) equipped with a refractive index detector (RID)
and a UV detector. The column used for the analysis was Rezex RPM-Monosaccharide Pb++
(Phenomenex, ø7.8 × 300 mm). The peak of H2SO4 was subtracted to determine the yield of
products. Optimisation of milling conditions is shown in ESI (Tables S1−S3).
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Preparation of 5 wt% Ru/TiO2.
Ru(NO)(NO3)3 solution (Wako) was added to aqueous dispersion of TiO2 (JRC-TIO-4(2),
Catalysis Society of Japan). After drying at 333 K at 60 hPa with a rotary evaporator, the sample
was further dried at < 1 Pa. The resulting powder was reduced under H2 flow (30 mL min−1) at
673 K for 2 h. Other supports tested in this work were ZrO2 (JRC-ZRO-5, Catalysis Society of
Japan) and carbon black (Black Pearls 2000, Cabot). The prepared catalysts were characterised
by X-ray diffraction (XRD; Rigaku, Ultima IV, Cu Kα, Figs. S1 and S2), transmission electron
microscopy (TEM; JEOL, JEM-2100F, 200 kV, Fig. S3) and N2 adsorption at 77 K (Table S1).
No peak for Ru was observed in the XRD patterns, which was due to high dispersion and
formation of amorphous RuO2⋅2H2O in air.20 Note that the oxidised Ru species is easily reduced
to metal under H2 atmosphere.21
One-step hydrolytic hydrogenation.
Oligomer-H2SO4 (454 mg), 5 wt% Ru/TiO2 catalyst (200 mg) and water (40 mL) were put
into a SUS316 high-pressure reactor (OM-Lab Tech, MMJ-100, 100 mL). After charging 4.0
MPa of H2, the temperature was raised from 298 to 453 K in 7 min. The rapid increase in
temperature is owing to no boiling of solvent under the pressurised condition. After reaching the
temperature, the reactor was quickly cooled down to room temperature by blowing air. This
thermal profile is described as rapid heating-cooling condition at 453 K hereafter. Products were
analysed with the HPLC system described above. Columns used for this analysis were SUGAR
SH-1011 column (Shodex, ø8 × 300 mm), Rezex RPM-Monosaccharide Pb++ column
(Phenomenex, ø7.8 × 300 mm) and Asahipak NH2P-50 4E (Shodex, ø4.6 × 250 mm). A gas
chromatograph with a flame ionisation detector (GC-FID; Shimadzu, GC-2025, column:
DB-FFAP) and that with a mass spectrometer (GC/MS; Shimadzu, GC-2010−Parvum 2,
column: HR-20M) were also utilised to determine volatile products.
Two-step hydrolytic hydrogenation.
Oligomer-H2SO4 (454 mg) and water (40 mL) were charged into the reactor. The hydrolysis
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reaction was performed under the rapid heating-cooling condition at a designated temperature,
in which heating up to the temperature took 10−14 min (e.g., 12 min to 448 K) in the absence of
H2 pressure. After finishing the hydrolysis, NaHCO3 and Ru/TiO2 (200 mg) were added to the
reaction mixture. The reactor was pressurised with 4 MPa of H2 prior to the hydrogenation
reaction at 393 K.
Results and discussion
Mechanocatalytic conversion of chitin to oligomer.
Mechanocatalytic hydrolysis of chitin was performed in the presence of H2SO4 at S/C of 3.4
by a planetary mill, where physisorbed water on the sample (11 wt%) was used for the
hydrolysis (Scheme 2, step 1). This reaction completely transformed chitin into water-soluble
compounds. Products were NAG in 19% yield and its oligomers in 64% yield, i.e., dimer (26%),
trimer (29%) and larger ones (9.0%) (Fig. 1). The amount of by-products was 17%, and HPLC
analysis detected dehydrated compounds such as 5-HMF. Formation of furanics was also
supported by NMR and UV-vis spectroscopy (Figs. S4, S5). The yields of NAG and oligomers
in this study were higher than those in the previous report (NAG 4.7%, dimer 7.8%, trimer
11%).14b This was due to larger contents of H2SO4 and physisorbed water in the sample in this
time (S/C = 3.4, water 11 wt%) than those in the previous case (S/C = 7.7, water 1.5 wt%).
Although too much water (>20 wt%) inhibits the mechanocatalytic hydrolysis by plasticising
effect,22 a small amount of physisorbed water facilitates hydrolysis and likely avoids
side-reactions by quickly trapping oxocarbenium ion intermediate. In addition, our condition did
not lead to the sticking of the sample on the wall of milling pot. This is a meaningful result for
upscaling, because the sticking is a considerable issue in a practical situation as reported by
Rinaldi and co-workers.23
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Fig. 1. Mechanocatalytic hydrolysis of chitin in the presence of acid catalysts.
Other liquid acids without intense oxidising or volatile properties were also tested to
elucidate the effect of acid strength in the mechanocatalytic hydrolysis. HClO4 (pKa = −10),
H2SO4 (−3), MeSO3H (−2) and perfluorobutyric acid (0.4) similarly converted chitin to NAG
and oligomers in 80−85% yield, where a stronger acid tended to give smaller oligomers (Fig. 1).
In contrast, H3PO4 (2.1) and acetic acid (4.7) provided low yields of 28% and <2%, respectively.
Accordingly, acids with pKa less than 1 were effective for the mechanocatalytic hydrolysis of
chitin. Dissociation of a glycosidic bond occurs after protonation of the oxygen atom (pKa ≈
−4)24 in the bond, which is the main cause to require a strong acid. We chose H2SO4 for the
mechanical reaction because of the highest degree of hydrolysis as well as the lowest price. The
resulting solid containing H2SO4 after the mechanocatalytic reaction was named
Oligomer-H2SO4.
One-step hydrolytic hydrogenation of Oligomer-H2SO4
Hydrolytic hydrogenation of Oligomer-H2SO4 was performed under H2 pressure of 4 MPa in
water under the rapid heating-cooling condition at 453 K (Scheme 2, step 2a). The catalyst for
hydrolysis was the H2SO4 contained in Oligomer-H2SO4 (S/C = 3.4), and pH of the reaction
solution became 2.0 in our condition. We added water-tolerant supported Ru catalysts in this
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reaction, as Ru is typically the most active metal species for the hydrogenation of sugars.25
Ru/TiO2 catalyst produced ADS in 25% yield (Table 1, entry 2), where the compound was
identified as ADS with NMR (Figs. S6 and S7) and GC/MS (Fig. S8). A turnover number
(TON) of surface Ru estimated by TEM (particle size 1−3 nm, dispersion 46%, Fig. S3) was 9
for the production of ADS. TEM was only the choice for this purpose, because XRD gave no
peak for Ru (Fig. S1) and CO pulse titration was less reliable due to coverage of Ru with
reduced TiOx in the pre-treatment, so-called strong metal-support interaction. By-products were
formed in large quantity (48%), the GC/MS analysis of which before and after
trimethylsilylation detected 2-amino-2-deoxysorbitol, acetic acid, acetamide,
N-acetylethanolamine, propylene glycol and ethylene glycol. Remaining part was unreacted
NAG (4.8% yield) and oligomers (22%). Ru/C and Ru/ZrO2 gave slightly lower yields of ADS
(21%, 19%, entries 3, 4). Adsorption of chitin oligomers and some of by-products on Ru/C
hampered handling of the catalyst. The axial face of chitin oligomers consists of lipophilic CH
groups, which facilitates adsorption of the oligomers on polycyclic aromatic surface of carbon
by CH−π hydrogen bonds and hydrophobic interactions.26 Basicity of ZrO227 is unfavourable for
the selective conversion of sugar molecules as described below. Accordingly, Ru/TiO2 was the
best catalyst for ADS production under the condition. A controlled reaction in the absence of
metal catalyst gave no ADS but produced NAG in 41% yield (entry 1). This yield is rather
higher than the total yield of NAG and ADS (30%) in the presence of Ru/TiO2, which suggests
that Ru promotes not only hydrogenation of NAG to ADS but also side-reactions.
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Table 1 Hydrolytic hydrogenation of Oligomer-H2SO4 by supported metal catalyst.a
Entry
Catalyst
Yield of product /%-NAG unit
ADS
0
NAG
41
Oligomer
Others
1
2
3
4
5
6
None
28
22
16
26
20
50
31
5 wt% Ru/TiO2
5 wt% Ru/C
5 wt% Ru/ZrO2
7 wt% Pt/TiO2
70 wt% Ni/TiO2
25
4.8
2.6
15
48
21
60 (26)b
40
19
2.9
0.3
49
28
29
21
aRapid heating-cooling condition at 453 K. Oligomer-H2SO4 454 mg, catalyst 200 mg, water 40
mL. p(H2) 4.0 MPa at 298 K. Characterisation data of catalysts are available in ESI. bAdsorbed
products.
We also tested Pt and Ni catalysts that showed good activity in the hydrolytic hydrogenation
of cellulose.27,28 However, Pt/TiO2 and Ni/TiO2 were inactive for the formation of ADS (2.9%
and 0.3% yields, respectively; entries 5 and 6), regardless of the higher loading amounts of
metals. Such a low activity of Pt was previously observed in the hydrolytic hydrogenation of
hemicellulose in beet fibre containing proteins.29 Pt is less active than Ru in the hydrogenation
of sugars, and amine by-products probably further deactivates Pt. Ni was oxidised by proton
under the acidic condition (Ni + 2H+ → Ni2+ + H2), which suppressed both hydrolysis and
hydrogenation. Thus, ADS yield was at most 25% in the catalyst screening (Ru/TiO2, entry 2).
The low yield of ADS is contrasting to the yield of sorbitol up to 90% in the hydrolytic
hydrogenation of cellulose and its oligomers despite their similar stuctures.30 Presence of amide
group drastically changes reactivity of the sugar molecule. Acetamide groups likely enhance the
reactivity of hemiacetal and subtraction of proton at C2 position due to the
electron-withdrawing effect. Moreover, the hydrolysis of acetamide produces amine, which
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easily causes side-reactions with sugars known as Maillard reaction.31
Two-step hydrolytic hydrogenation of Oligomer-H2SO4
The one-step hydrolytic hydrogenation caused side-reactions. To overcome this issue, we
designed a one-pot but two-step reaction consisting of hydrolysis of Oligomer-H2SO4 to NAG
and subsequent hydrogenation to ADS under the optimised conditions in the respective steps
(Scheme 2, steps 2b and 3ab). For the hydrolysis step, as the reaction prefers short time and
high temperature to maximise NAG yield,14b we tested the rapid heating-cooling condition at
different temperatures (Fig. 2). Yield of NAG increased by raising the reaction temperature and
reached 61% at 448 K. In this case, TON of H2SO4 was 2.3 for the production of NAG, showing
that H2SO4 functioned as a catalyst under our condition. Further increase in temperature
decreased yield of NAG due to the successive decomposition, where dark brown colour of the
reaction mixture indicated the formation of humins.
Fig. 2. Effect of reaction temperature on the hydrolysis of Oligomer-H2SO4.
The reaction solution after the hydrolysis at 448 K, the temperature maximising the yield of
NAG, was directly used for the subsequent hydrogenation reaction (Scheme 2, step 3a). We
performed the reaction at a low temperature of 393 K, because a lower temperature generally
gives higher selectivity in hydrogenation of sugars.16, 32 Reduction of NAG to ADS proceeded in
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a first-order manner in the presence of Ru/TiO2 and 4 MPa of H2 (Fig. 3a). Overall yield of ADS
reached 37% at 2 h with 62% selectivity based on the consumed amount of NAG, and ADS was
slowly decomposed in a longer reaction time. Thus, the two-step reaction increased the ADS
yield 1.5 times higher than the one-step reaction (25%). However, side-reaction was still
significant compared to the hydrogenation of pure NAG by Ru/TiO2 in water (93% selectivity at
0.5 h; Fig. 3f).
Fig. 3. Time courses of hydrogenation of Oligomer-H2SO4 hydrolysate at 393 K. (a) pH 2.0 (=
no neutralisation), (b) pH 3.0, (c) pH 4.0, (d) pH 5.0, (e) pH 6.8. (f) That of pure NAG in water,
where the amount of NAG was the same as that in the chitin conversion (61%). Lines indicate
simulation results.
The side-reactions in the hydrogenation of Oligomer-H2SO4 was presumably due to H2SO4
(pH 2.0), which motivated us to conduct the reaction after adding NaHCO3 to adjust pH
(Scheme 2, step 3b). The overall yield of ADS was increased to 52% at pH 3 and 51% at pH 4
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with improved hydrogenation selectivity of >85% (Fig. 3b, c). As expected, the selectivity
approached that in the conversion of pure NAG in water. We speculate that the milder acidic
condition suppresses the hydrolysis and hydrogenation of amide (Scheme S1) and the
decomposition of hemiacetal by H+ and Ru. Owing to the higher selectivity, TON of surface Ru
also increased to 19. Note that the hydrogenation reaction took a longer time (2 h) than that of
pure NAG (0.5 h), which was attributed to the inhibition effect of by-products as discussed
above. This was also observed in the reuse experiment of Ru/TiO2 used at pH 3, where the
catalyst showed lower activity due to further adsorption of catalyst poison in the second run (Fig.
S9). However, the structure of catalyst (Fig. S10) or catalytic activity did not change during the
time course in one reaction as indicated in the kinetic analysis described below. Further increase
in pH to 5.0 slightly lowered the yield of ADS (46%; Fig. 3d), and the reaction at pH 6.8
drastically decreased the yield to 5% (Fig. 3e). The neutral condition produced large amounts of
N-acetylethanolamine (31% [mol-product/mol-NAG unit]) and erythritol (16%) via retro-aldol
reaction of NAG due to presence of HCO3− (Scheme 3). HCO3− is remaining at pH 6.8 because
−
pKa of the conjugated acid (H2CO3; 6.3) is lower than the pH value. In addition, HCO3
spontaneously forms a stronger base by the disproportionation (2HCO3− → CO32− + CO2 + H2O)
at a high temperature. Indeed, the hydrogenation of pure NAG after adding H2SO4 and NaHCO3
(pH 6.8) gave N-acetylethanolamine and erythritol. Neutralisation with NaHCO3 to pH 7 is
inappropriate for the synthesis of ADS, but slightly acidic condition is the best option.
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Scheme 3. Formation of erythritol and N-acetylethanolamine from NAG. B−: base.
The pseudo first-order rate constants were determined for the hydrogenation of NAG to ADS
(k1), NAG to by-product (k2) and ADS to by-product (k3) by curve-fitting of the actual
experimental results (Table 2). Increase in pH from 2 to 3 had little influence on k1 value, but k2
decreased from 0.56 h−1 to 0.08 h−1 and k3 reduced from 0.05 h−1 to 0.03 h−1. Kinetic simulation
shows that k2 affects ADS yield more strongly than k3 (Table 3). Specifically, decrease in k2
from 0.56 to 0.08 h−1 increases the yield by 12−13%, whereas that in k3 from 0.05 to 0.03 h−1
gains 1−2%. Further increase in pH to 4−5 gave minor influence on the rate constants, but k2
was dramatically elevated up to 4.6 h−1 at pH 6.8 due to acceleration of the aldol reaction as
described above. Hence, the minimisation of k2, more accurately the ratio of k2/k1, is the major
factor to maximise the yield of ADS at pH 3−4.
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Table 2 Kinetic parameters determined by curve fitting of the reaction time courses.
k1 /h−1
1.4
k2 /h−1
k3 /h−1
pH
2.0
3.0
4.0
5.0
6.8a
0.56
0.050
1.3
0.080 0.030
0.050 0.025
1.0
0.95
0.60
0.15
4.6
0.020
0.10
aHCO3− was present, which was different from pure water.
Table 3 Simulation of effects of kinetic parameters on ADS yield.
k1 /h−1
k2 /h−1
k3 /h−1
Theoretical maximum
Time /h
2.0
ADS yielda /%
1.3
1.3
1.3
1.3
0.56
0.56
0.08
0.08
0.05
0.03
0.05
0.03
39
40
51
53
2.3
2.5
2.8
1
R



k1
1
a Max. ADS yield = M NAG
R
− R1−R , where MNAG = initial amount of NAG =
1−R





k1 + k2 R −1
61%, R = k3/(k1+k2) ≠ 1. This formula is established by solving differential equations about
kinetics. See ESI.
Conclusions
Catalytic conversion of chitin was studied to produce ADS without purifying intermediates.
Planetary ball-milling of chitin gives NAG and oligomers in 83% yield by mechanocatalytic
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hydrolysis in the presence of H2SO4. Ball-milling is known to be an energy-consuming process,
but the scale-up drastically increases the efficiency.23 The ball-milled sample (Oligomer-H2SO4)
can be directly converted to ADS by the hydrolytic hydrogenation by Ru/TiO2. However, the
yield of ADS is at most 25% in this method, which is remarkably different from selective
conversion of cellulose to sorbitol. An amide group in NAG drastically changes the reactivity of
sugar molecule. Selectivity for ADS is improved by separating the hydrolysis and the
hydrogenation steps to optimise both reactions. The hydrolysis is enhanced at high temperature
(448 K) and low pH (2.0), while the hydrogenation requires low temperature (393 K) and
careful control of pH. In the hydrogenation step, low pH (2.0) results in various side-reactions
of amide and hemiacetal groups especially in the presence of Ru catalyst, whereas high pH (6.8)
induces retro-aldol reaction to form erythritol and N-acetylethanolamine due to presence of
basic species. Therefore, partial neutralisation of the solution to pH 3−4 maximises the
hydrogenation selectivity and overall yield of ADS up to >85% and 52%, respectively. The
produced ADS might be isolated from the reaction mixture by removing by-products with
ion-exchange resin and activated carbon followed by crystallisation. The kinetic analysis has
indicated that ADS is relatively stable under the reaction conditions. Hence, development of a
durable hydrogenation catalyst that selectively and rapidly converts NAG to ADS even at high
temperature and low pH would be promising for more efficient synthesis of ADS.
Acknowledgments
We utilised NMR and TEM at the Open Facility of Institute for Catalysis (ICAT), Hokkaido
University, and the TEM measurement was assisted by the technical division of ICAT. This
work was supported by Grant-in-Aid for Young Scientist (A) (No. 26709060) from the Japan
Society for the Promotion of Science (JSPS).
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