CHEMICAL ENGINEERING TRANSACTIONS  
 

VOL. 76, 2019 

A publication of 

 

The Italian Association 
of Chemical Engineering 
Online at www.aidic.it/cet 

Guest Editors: Petar S. Varbanov, Timothy G. Walmsley, Jiří J. Klemeš, Panos Seferlis 
Copyright © 2019, AIDIC Servizi S.r.l. 

ISBN 978-88-95608-73-0; ISSN 2283-9216 

Ni Impregnated into Hypercrosslinked Polystyrene for  

N-Methyl-D-Glucosamine Synthesis 

Stepan Mikhailova,b, Valentin Doludab,*, Esther Sulmanb, Natalia Lakinab, Valentina 

Matveevaa,b, Mikhail Sulmanb 

aTver State University, 170100, Zhelyabova str., 33, Tver, Russia 
bTver State Technical University, 170026, A. Nikitina, 22, Tver, Russia 

 doludav@yandex.ru 

D-glucose simultaneous catalytic hydro condensation with methylamine can be considered a promising way of 

N-methyl-D-glucosamine synthesis. In the current work, the use of novel polymeric nickel-based catalyst is 

proposed for the production of N-methyl-D-glucosamine in one step through reductive amination. The one-step 

N-Methyl-D-glucosamine synthesis was performed in a batch reactor using heterogeneous catalyst based on 

the polymeric matrix of hypercrosslinked polystyrene. The experiments on varying of temperature (80 – 140 °C), 

Ni loading (10 – 25 wt. %), D-glucose initial concentration (0.8 – 1.6 mol/L), and hydrogen pressure (40 – 60 

bar) were performed in order to find optimal reaction conditions. The initial catalyst activity was found to be 1.3 

kg(Glu)/(kg(Cat)*h). Catalysts activity after 10 cycles of D-glucose transformation showed a little slowdown and 

was calculated to be 1.1 kg(Glu)/(kg(Cat)*h) at 99.4 – 99.5 % D-glucose conversion.  

1. Introduction 

Amines are one of the key intermediates for a synthesis of different substances and polymers. Typically, amines 

can be synthesized by the direct amination of alcylhalogenides. Another way to produce amines is the direct 

amination of alcohols (Froidevaux et al., 2016). However, these methods involve the oil- or natural gas-based 

substrates for the amination.  

The modern tendencies in the use of bio-derived feedstock for the synthesis of amines are of great interest. 

Chitosan is one of the most important biopolymers which can be used for the synthesis of amines. However, 

the limitation of the chitosan resources makes the problem of a search of novel routes for the production of bio-

based amines (Froidevaux et al., 2016). Among the different bio-based feedstock for amine synthesis, the sugar 

derivatives are the most promising. There are two main routes for the conversion of sugars into bio-based 

amines: (i) reductive amination of carbonyl compounds, and (ii) amination of sugar alcohols (Pelckmans et al., 

2017). 

There are some researches devoted to the conversion of sugars and their derivatives into amines. Pera-Titus 

and Shi (2014) reported the application of ruthenium and iridium catalysts for the amination of sugar alcohols. 

Another research was done by Pingen et al. (2013) which used Ru/C catalyst for direct amination of bio-based 

polyols into the primary amines at high temperature. An alternative way to produce bio-based amines was 

proposed by Sieber et al. (2010) in order to produce aminated isosorbide. This way was based on the reductive 

amination was also performed by Montgomery and Wiggins (1946).  

Reductive amination involves the transformation of C=O bonds into C-N bonds and is typically conducted in two 

steps. First, the imine is formed from the sugar and ammonia or primary amine. Then, the resulted imine is 

reduced by molecular hydrogen or hydrogen donors (Hutchins and Hutchins, 1991). This step is performed in 

the presence of hydrogenation catalysts (Gomez et al., 2002).  

Сatalytic D-glucose hydro condensation with methylamine can be used for methyl-glucosamine synthesis 

(Shumate et al., 1992). Methylamine reacts with reducing sugars in methanol to prepare N-

alkylpolyhydroxyimines. Glucose is reacted with methylamine and the resulting adduct is hydrogenated to yield 

N-methylglucamine. The production of N-methylglucamine as early as 1935 was patented by American 

 
 
 
 
 
 
 
 
 
 
                                                                                                                                                                 DOI: 10.3303/CET1976145 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Paper Received: 16/03/2019; Revised: 15/04/2019; Accepted: 24/04/2019 
Please cite this article as: Mikhailov S., Doluda V.Y., Sulman E.M., Lakina N., Matveeva V.G., Sulman M.G., 2019, Ni Impregnated into 
Hypercrosslinked Polystyrene for N-Methyl-D-Glucosamine Synthesis, Chemical Engineering Transactions, 76, 865-870  
DOI:10.3303/CET1976145 
  

865

mailto:doludav@yandex.ru


scientists Robert B. Flint and Paul L. Salsberg, the rightful owner is the large chemical company E. I. du Pont 

de Nemours & Company (Scheibel et al., 1992). The reaction for the production of N-methylglucamine by 

reductive amination proceeds in one or two steps (Figure 1). 

 

C

C OHH

OH

C OHH

C HHO

C OHH

CH2OH

CH3NH2+

D-glucose

C

C OHH

NH

C OHH

C HHO

C OHH

CH2OH

CH3

+H2
[Cat]

C

C OHH

NHH

C OHH

C HHO

C OHH

CH2OH

CH3

n-methyl-D-glucoseimine n-methyl-D-glucoseamine 

Figure 1: Scheme of N-methyl-D-glucosamine synthesis 

As can be seen, there is a limited amount of the researches for the production of bio-based amines. These 

studies practically do not provide any information about the yield of the amines. Moreover, in the hydrogenation 

step, Ru is the most frequently used catalyst. As Ru is quite expensive, the search of the cheaper metal for the 

hydrogenation catalyst is one of the key tasks for the reductive amination of bio-based molecules. In the current 

work, the use of novel polymeric nickel-based catalyst is proposed for the production of N-methyl-D-glucosamine 

in one step. 

2. Materials and methods 

2.1 D-glucose transformation reaction in a batch reactor 

Figure 2 shows a high-pressure vessel produces by Parr Instrument Inc., USA. for the catalytic transformation 

of D-glucose into N-methyl-D-glucosamine. Typically 30 g of D-glucose places in the reactor vessel, and then 

150 mL of methanol and 13 mL of 40 wt. % methylamine and 10 g of catalyst were feed into the reactor. Then 

reactor flushed with nitrogen three times and heated to 120 °C with further purging of the reactor with hydrogen. 

The experiments on varying of temperature (80 – 140 °C), Ni loading (10 – 25 wt. %), D-glucose initial 

concentration (0.8 – 1.6 mol/L), and hydrogen pressure (40 – 60 bar) were performed in order to find optimal 

reaction conditions. 

 

 

Figure 2: Reaction vessel for D-glucose transformation to N-methyl-D-glucosamine. 1 – Parr instrument high-

pressure reactor, 2 – controller, 3 – tank for nitrogen, 4 – tank for hydrogen, 5 – heater, 6 – pressure reducer. 

866



Samples of the reaction mixture were taken during the reaction and were analyzed using thin layer plate 

chromatography followed by UV visualization. 

2.2 Catalysts synthesis 

Samples of 10, 15, 25 wt % nickel supported hypercrosslinked polystyrene (HPS) were synthesized as the 

following: pre-calculated amount of Ni(CH3COO)2 was added to 250 mL of distilled water under a constant 

stirring, then 30 g of HPS (MN-100) was added partially to the solution of Ni(CH3COO)2. Samples were treated 

using the ultrasonic bath at 80 °C with further drying at 105°C. Before using the catalysts were reduced with 

hydrogen in the tube furnace at 300 °C for 6 h. In order to prevent oxidation, the catalysts were transferred to 

the reactor in argon. 

2.3 Hydrogen chemisorption 

Determination of catalyst metal active sites quantity was based on the measurement of the amount of hydrogen 

adsorbed on the catalyst surface. The Chemosorb 4580 gas chemisorption analyzer (Micromeritics, USA) was 

used for the study. The sample was placed in a quartz cuvette and blown with helium at a temperature of 300 

°C, after cooling the sample to a temperature of 50 °C gas mixture of hydrogen and helium was adsorbed over 

catalysts surface. Further desorption of hydrogen was provided at a temperature increasing up to 300 °C with a 

heating rate 10 °C/min. The amount of adsorbed hydrogen was determined using a thermal conductive detector 

and a previously made calibration line. 

2.4 Determination of the catalyst surface area 

Determination of the catalyst surface area was performed by low-temperature nitrogen sorption. The nitrogen 

adsorption isotherm was made using the volumetric method implemented in the Beckman Coulter gas sorption 

analyzer (Coulter Corporation, USA). The surface area of the micro and mesoporous catalysts was calculated 

using the t-plot model. 

2.5 X-ray photoelectron spectroscopy of catalysts 

XPS spectra were obtained using a spectrometer ES 2403 M-T modified with analyzer PHOIBOS 100 (SPECS, 

Germany). For photoelectron extraction, the characteristic MgK-α line was used (hν = 1253.6 eV). The data 

analysis was performed by CasaXPS. Mathematical modeling of the Ni 2p sublevel was performed using Shirley-

Marcward equation. 

3. Results and Discussions 

Investigation of synthesized catalysts activity Ni - 10 wt. % - HPS, Ni - 15 wt. % - HPS and Ni - 25 wt. % - HPS 

is presented in Figure 3. The increase of nickel loading results in an appropriate increase of methylglucimine 

and methylglucamine formation rate. The sample Ni - 25 wt. % - HPS showed the highest activity therefor all 

further experiments were provided using this sample. 

Time, h

0 1 2 3 4 5 6 7

M
e

th
y
lg

lu
ti
m

in
e
 c

o
n
c
e

n
tr

a
ti
o

n
, 

m
o

l/
l

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

Ni-25-wt.%-HPS

Ni-15-wt.%-HPS

Ni-10-wt.%-HPS

а)

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ta

m
in

e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.0

0.2

0.4

0.6

0.8

Ni-25-wt.%-HPS

Ni-15-wt.%-HPS

Ni-10-wt.%-HPS

b)

 

Figure 3: Investigation of synthesized catalysts activity for a) N-methyl-D-glucosimine, b) N-methyl-D-

glucosamine yield.  

During the experiments N-methyl-D-glucoseimine, N-methyl-D-glucosamine were found in the reaction media 

and can be considered as main products, sorbitol was found as a main side product. Investigation of temperature 

influence on N-methyl-D-glucosimine and N-methyl-D-glucosamine yield is presented in Figure 4. Increase in 

867



the reaction temperature results in an appropriate increase in N-methyl-D-glucosimine and N-methyl-D-

glucosamine yield (Figure 4a and 4b). 

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ti
m

in
e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

t=800C

t=1000C

t=1200C

t=1400C

а)

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ta

m
in

e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.0

0.2

0.4

0.6

0.8

t=800C

t=1000C

t=1200C

t=1400C

b)

 

Figure 4: Temperature influence on a) N-methyl-D-glucosimine, b) N-methyl-D-glucosamine yield.  

For determination of the processes activation energies Arrhenius equation plot was made (Figure 5). 

Determined specific activation energies were found to be 39±7 kJ/mol and 30±9 kJ/mol for N-methyl-D-

glucosimine and N-methyl-D-glucosamine synthesis process. 

1/T

0.0028 0.0029 0.0030 0.0031 0.0032 0.0033 0.0034

ln
(K

)

2.5

3.0

3.5

4.0

4.5

5.0

n-methyl-D-glucoseimine

n-methyl-D-glucoseamine

 

Figure 5: Arrhenius plot for N-methyl-D-glucosimine and N-methyl-D-glucosamine formation.  

Influence of D-glucose concentration on N-methyl-D-glucosimine and N-methyl-D-glucosamine yield is 

presented in Figure 6. Increasing of D-glucose initial concentration from 0.8 mol/L to 1.6 mol/L results in 

increasing of N-methyl-D-glucosimine and N-methyl-D-glucosamine formation rates.  

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ti
m

in
e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

С
ini

(D-Glucose)=1.6 mol/l

С
ini

(D-Glucose)=1.2 mol/l

С
ini

(D-Glucose)=0.8 mol/l

а)

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ta

m
in

e
 c

o
n
c
e
n
tr

a
ti
o
n
, 
m

o
l/
l

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

С
ini

(D-Glucose)=1.6 mol/l

С
ini

(D-Glucose)=1.2 mol/l

С
ini

(D-Glucose)=0.8 mol/l

b)

 

Figure 6: D-glucose initial concentration influence on a) N-methyl-D-glucosimine, b) N-methyl-D-glucosamine 

yield.  

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Influence of hydrogen pressure on N-methyl-D-glucosimine and N-methyl-D-glucosamine yield is presented in 

Figure 7. Increase in hydrogen partial pressure from 40 to 60 bar results in an increase in N-methyl-D-

glucosimine and N-methyl-D-glucosamine formation rates.  

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ti
m

in
e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

p(H2)=40 Bar

p(H2)=60 Bar

p(H2)=80 Bar

а)

Time, h

0 1 2 3 4 5 6 7

M
e
th

y
lg

lu
ti
m

in
e
 c

o
n
c
e
n
tr

a
ti
o
n
, 

m
o
l/
l

0.0

0.2

0.4

0.6

0.8

p(H2)=40 Bar

p(H2)=60 Bar

p(H2)=80 Bar

b)

 

Figure 7: Hydrogen pressure influence on a) N-methyl-D-glucosimine, b) N-methyl-D-glucosamine yield.  

Determination of reaction order of N-methyl-D-glucosamine synthesis on hydrogen and D-glucose was provided 

using kinetic curves of the logarithm of reaction rate vs logarithm of D-glucose concentration and logarithm of 

hydrogen pressure (Figure 8). Founded partial reactions order was near to one that suggests monomolecular 

surface reaction. 

LN(Cini D-glucose),

-0.1 0.0 0.1 0.2

L
N

(W
)

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

LN(W)= 0.9958LN(C
ini

) + 0.2074 а)

LN(pH
2
)

1.6 1.7 1.8 1.9

L
N

(W
)

-0.25

-0.20

-0.15

-0.10

-0.05

0.00

0.05

0.10

0.15

LN(W)= 0.99LN(pH
2
) - 1.758 b)

 

Figure 8: Determination of partial apparent reaction order for N-methyl-D-glucosamine synthesis for (a) D-

glucose, (b) hydrogen.  

The investigation of the catalysts long term stability showed that after 10 reaction cycles of 6 hours 

hydrogenation the HPS-Ni catalyst was ground by a reactor mixer, therefore, catalysts particles diameter 

becomes smaller than 0.01 – 0.07 mm compare to the initial (Table 1). Besides the catalysts mechanical losses 

were calculated to be 78 %, the catalyst weight losses can be attributed to the catalysts particles grinding and 

losses during the centrifugation and separation. The catalysts activity after 10 cycles of D-glucose 

transformation showed a little slowdown and was calculated to be for 1.1 kg(Glu)/(kg(Cat)*h) at 99.4 – 99.5 % 

D-glucose conversion. Some losses of catalysts activity can be attributed to metal leaching. However, some 

increase in Ni dispersion is noticed that can be also explained by the catalyst particles grinding and particles 

transformation during the reaction. The oxidation state of an active metal according to XPS data remains +2 

and Ni is mainly presented in the oxide form.  

 

 

869



Table 1 Catalysts characteristics of the used catalyst  

Catalyst characteristics Before synthesis After synthesis 

Surface area, m2/g 240 187 

Granulometric composition, mm 0.1-0.12 0.1-0.14 

Nanoparticles size, nm 4-16 4-12 

Ni oxidation state 0, +2 +2 

Ni concentration, wt. % 2.3 2.4 

Ni dispersion, % 25 27 

Sample mass losses, wt. % 27 12 

4. Conclusions 

D-glucose simultaneous catalytic hydro condensation with methylamine can be considered a promising way of 

methylglucamine synthesis. Amines such as methylamine are reacted with materials such as reducing sugars 

in hydroxy solvents such as methanol to prepare N-alkyl polyhydroxy amines. Accordingly, glucose is reacted 

with methylamine and the resulting adduct is hydrogenated to N-methylglucamine. Catalysts initial activity of Ni 

impregnated in hypercrosslinked polystyrene was found to be 1.3 kg(Glu)/(kg(Cat)*h) at 99.3 – 99.6 % D-

glucose conversion. Process selectivity to N-methyl-d-glucosamine was 97.6 – 97.8 %. Sorbitol was found in 

traces during the analysis and can be considered the main side products. Some losses of catalysts activity can 

be attributed to metal leaching. However, some increase in Ni dispersion is noticed that can be also explained 

by the catalyst particles grinding and particles transformation during the reaction. The oxidation state of an active 

metal according to XPS data remains +2 and Ni is mainly presented in the oxide form.  

Acknowledgments 

This study was funded by the Russian Science Foundation (grant No 18-19-00240) and the Russian Foundation 

for Basic Researches (grant No 17-08-00568). 

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