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The quartenizeid chloride derivative of natural polyaminosaccharide chitosan was synthesized in two stages with acetate aldehyde and methyl iodide chemical reaction and ion replacement, which could be soluble in the water and wide pH ranges. The synthesis of the homopolymer was initially carried out with acetate aldehyde in Schiff reaction, and reduction was held on with the presence of NaBH4. The quaternization was accomplished in the acetonitrile medium with methyl iodine by continuous exposure of N2.7-8% quartenized N,N-diethyl, N-methyl chitosan iodine were synthesized with 89-91% yield, obtained by deprotonation of amine groups, with reaction of CH3J and N,N-diethyl chitosan. The ion exchange was carried out at 10% NaCl solution during 24 hours and N,N-diethyl, N-methyl chitosan chloride was obtained. Synthesis was performed with simpler and chemically effective methods compared to previous studies. The structure of product was characterized by FT-IR, UV-Vis, NMR, SEM, TGA, DTA and elemental analysis was determined. Functional changes in the structure of macromolecules were monitored with NMR and UV-Vis, and it was proved that, the main intermediate product was composed to be N,N-diethyl carbocation carrying >C=N- chromophore group. The increasing percent of carbon in content while alkylation is depeering and the presence of halogenated ions (Cl- or J-) after quaternization were observed. It has been determined that, the solubility of N,N-diethyl,N-methyl chitosan chloride or iodide in water and in pH =1-10 increased frequently.
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Synthesis of N,N-Diethyl, N-Methyl Chitosan Chloride with Certain
Quaternization Degree and Molecular Spectroscopic and Thermo-
Morphological Study of the Alkylation
Sh.Z. Tapdigov1,a*, S.F. Safaraliyeva2,b, P. Theato3,c, N.A. Zeynalov4,d,
D.B. Tagiyev5,e, M.G. Raucci6,f and M.X.Hasanova7,g
1Ph.D, Post Doc. of Azerbaijan National Academy of Sciences Institute Catalysis and Inorganic
Chemistry, Department of Nanostructured Metal-Polymer Catalysist,
Baku AZ1143, H.Javid ave.113, Tel:+994125107442, Fax: +994125108593,
2Ph.D student of Institute of Catalysis and Inorganic Chemistry Named After Acad.M.Nagiyev,
Azerbaijan, Baku AZ1143, H.Javid ave.113, Tel: +9940507205072, E-mail:
3Karlsruhe Institute of Technology Institut Für Technische Chemie Und Polymerchemie, Germany,
Engesser Str. 18, Gebäude 11.23, D-76131 Karlsruhe, Tel: +4972160845159,
Fax: +4972160845740
4Prof., Head of Department of “Nanostructured Metal-Polymer Catalysist”, of Azerbaijan National
Academy of Sciences Institute Catalysis and Inorganic Chemistry, Baku AZ1143, H.Javid ave.113,
Tel:+9940506752710, Fax: +994125108593
5Academician, Director of named after acad. M.Nagiyev Institute of Catalysis and Inorganic
Chemistry, vice president of ANAS, academician-secretary of Department of Chemical
Sciences, Azerbaijan, Baku AZ1143, H.Javid ave.113, Tel: +994125399382, Fax: +994125108593
6Institute of Polymers, Composites and Biomaterials, Yiale J.F. Kennedy 54 Mostra d’Oltremare
pad. 20, 80125 Naples Italy, Tel: 081 2425945, Fax: 081 2425932
7Ph.D student of Institute of Catalysis and Inorganic Chemistry Named After Acad.M.Nagiyev,
Azerbaijan, Baku AZ1143, H.Javid ave.113, Tel: +9940556538280
a*shamo.chem.az@gmail.com, bsafaraliyeva2017@mail.ru, cpatrick.theato@kit.edu,
dzeynalovnizami3@gmail.com, ekqki@kqki.science.az, fmariagrazia.raucci@cnr.it,
gmirvarihesen@gmail.com
Keywords. Chitosan; alkylation; diethylmethyl chitosan iodine; quartenization; UV-Vis; NMR
Abstract. The quartenizeid chloride derivative of natural polyaminosaccharide chitosan was
synthesized in two stages with acetate aldehyde and methyl iodide chemical reaction and ion
replacement, which could be soluble in the water and wide pH ranges. The synthesis of the
homopolymer was initially carried out with acetate aldehyde in Schiff reaction, and reduction was
held on with the presence of NaBH4. The quaternization was accomplished in the acetonitrile
medium with methyl iodine by continuous exposure of N2.7-8% quartenized N,N-diethyl, N-methyl
chitosan iodine were synthesized with 89-91% yield, obtained by deprotonation of amine groups,
with reaction of CH3J and N,N-diethyl chitosan. The ion exchange was carried out at 10% NaCl
solution during 24 hours and N,N-diethyl, N-methyl chitosan chloride was obtained. Synthesis was
performed with simpler and chemically effective methods compared to previous studies. The
structure of product was characterized by FT-IR, UV-Vis, NMR, SEM, TGA, DTA and elemental
analysis was determined. Functional changes in the structure of macromolecules were monitored
with NMR and UV-Vis, and it was proved that, the main intermediate product was composed to be
N,N-diethyl carbocation carrying >C=N- chromophore group. The increasing percent of carbon in
content while alkylation is depeering and the presence of halogenated ions (Cl- or J-) after
quaternization were observed. It has been determined that, the solubility of N,N-diethyl,N-methyl
chitosan chloride or iodide in water and in pH =1-10 increased frequently.
Journal of Biomimetics, Biomaterials and Biomedical Engineering Submitted: 2018-04-20
ISSN: 2296-9845, Vol. 39, pp 77-88 Revised: 2018-09-18
doi:10.4028/www.scientific.net/JBBBE.39.77 Accepted: 2018-09-18
© 2018 Trans Tech Publications, Switzerland Online: 2018-11-05
All rights reserved. No part of contents of this paper may be reproduced or transmitted in any form or by any means without the written permission of Trans
Tech Publications, www.scientific.net. (#112071087-06/01/19,17:33:01)
1. Introduction
Chitosan is a linear cationite type natural polyaminosaccharide produced by N-deacetylation of
chitin [1-3]. Chitin is separated from dense chitin coatings of some insects, molluscs, in particular,
crustaceans. Chitosan consists of β-(1,4)-2-amino-2-deoxy-D-glucosamine and β-(1,4)-N-acetyl D-
glucosamine units [4-7].
The non-toxicity, biocompatibility, biodegradation and bone adhesion of chitosan confirm its
perfect properties in transportation of genes and drugs in medicine and biotechnology, stabilization
of antibacterial metal nanoparticles [8,9]. Solubility of chitosan only in acidic environment limits its
use as a carrier in controlled release of some drugs. Degree of N-acetylation and the distribution of
the N-acetyl groups depends on the physical properties of chitosan [10]. Chitosan derivatives with
new properties were synthesized by graft copolymerization, acylation, carboxymethylation, N-
phosphonomethylation and other chemical reactions of chitosan macromolecule [11-13]. Such
derivatives have new properties and can be managed from a molecular structural and can easily
enter into electrostatic or hydrogen bond with low molecular drug preparations. N-alkylation or O-
methylation degree of amine groups in chitosan macromolecule is of great importance. Several
studies had been conducted to obtain citosan with desired properties.
In 1984 Muzzarelli and Tanfani [14] synthesized N-trimethyl chitosan chloride, the solubility of
which is increased in water and buffer solutions by methylation and then quaternization of chitosan
with formaldehyde. However this synthesis was performed for a longer period and optimum value
of quaternization degree remained open. The resultant product exhibited high sorption capacity in
ion substitution of some metal ions. Pardeshi V.C. and others [15] performed controlled synthesis of
N-trimethyl chitosan for modulating nasal membrane permeability and bioadhesion of chitosan.
They showed that dissolution, swelling degree, viscosity and bioadhesion potential of chitosan were
increased. In other work [16] a new method was proposed to produce trimethyl ammonium salt of
chitosan using dimethyl carbonate as a quaternizing agent. 9-11% of chitosan was quaternized,
crystallinity decreased, N-methylation degree increased, its thermal stability relative to chitosan
increased. Rolf J.Verheul and others [17] synthesized trimethyl chitosan of various degrees of
quaternization by achieving N-methylation and O-methylation of chitosan simultaneously. O-
methyl free trimethyl chitosan with 33% quaternization degree exhibits high solubility in water.
This modification causes the increase of cytotoxicity and membrane permeability of chitosan.
Mar Masson [18] has developed high chemical selective synthesis of N-trimethyl chitosan. Di-tert-
butyldimethycillil-3,6-O-chitosan was used as a precursor and optimum condition of synthesizing
N-alkyl, N,N-dimethyl chitosan derivative with 65-72% yield was determined.
Compared research works show that effective chemical pure alkylation and then quaternization of
amine groups of chitosan with alkyl halides were performed using different methods. When
usefulness of the synthesis process, toxicity of methylation reagents, reaction time, temperature and
other parameters are changed new properties appear. However in these studies molecular structure
of products, reaction mechanism, details of reduction process during stepwise course of N-
alkylation reaction have not been shown. In the present study, diethylation and quaternization of
chitosan with methyl iodide by two-stage process was performed, element analysis, structure of
intermediate homopolymer N,N-diethyl chitosan were identified by spectroscopic methods, surface
morphology and thermal stability were determined using modern devices. N,N-diethylation and
reduction of chitosan with NaBH4, its quaternization, mechanism of reactions was defined and
molecular structure of resultant products was determined by high sensitive UV-Vis and NMR-
spectroscopic methods.
78 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
2. Experiments
2.1 Materials
Chitosan Mn=35 kDa (deacetylating degree 85-87%), acetic aldehyde ( ≥99.0%), NaBH4 (purum
p.a., ≥96%), acetate acid (Glacial), ethanol (95%), acetone (residue analysis, ≥99.9%), diethyl ether
(contains 1 ppm BHT as inhibitor, anhydrous, ≥99.7%), NaCl (BioXtra, ≥99.5%), acetonitrile
(anhydrous, 99.8%) from Sigma-Aldrich. Methyl iodide (99%) is from Acros Organics stabilized
with copper.
2.2 Synthesis of N,N-diethyl, N-methyl chloride chitosan
The synthesis of N,N-diethyl,N-methyl chitosan was conducted in two stages - initially by
alkylation and then by the reduction process. Synthesis was performed on the known methodology
[19] based on Schiff reaction. Unlike previous methods, a clean, effective and reliable procedure
has been used in synthesis. 3 g of chitosan is suspended in 120 ml 2% CH3COOH solution
(containing 14.58 mmol -NH2 group). 1.63 ml acetate aldehyde is added intensively to the solution
in the form of drops of - twice more than the equivalent molar ratio. After 30 min the color of the
solution varies from light brown to yellow. The mixturing is continued in an inert N2 environment
for 5 days. At the end the solution is turned into a dark brown gel. After the gel was grinded and
waited for 12 hours, 0.78 g NaBH4 was dissolved in 8 ml water and added to the solution by
dropping over 7-8 hours under intensive mixing. At that time, the pH of the solution is contained
4.0-4.5. After 8 hours, the pH of the solution is brought to 10 by added 1M KOH, then the gel is
formated. Gel is first washed with distilled water then with ethanol, collapsed in acetone, and
extracted with diethyl ether at Soxlet for 3 days. Then, gel was dried overnight until constant weight
at 40-50 0C after extraction, and freeze dried in vacuum for 24 hrs. 2 g N,N-diethyl chitosan is
mixed in 40 ml acetonitrile for 30 minutes at 35 0C for quaternization. The, 1 ml CH3J was dropped
in nitrogen atmosphere under vigorous stirring for 30 hours at 35 0C. At the end, the gel was filtered
and washed with alcohol and acetone and extracted in Soxlet with dietyl ether for 2 days, dried at
40 0C for 24 hours until constant weight and vacuum dried. The ion exchange was carried with
stirring of 1.5 g N, N-diethyl, N-methyl chitosan iodine and 50 mL of 10% NaCl solution for 24
hours, and N,N-diethyl,N-methyl chitosan chloride was obtained. The product is again washed with
alcohol acetone, extracted in diethyl ether and dried.
2.3 Spectroscopic Characterization of N, N-diethyl N-Methyl Chloride Chitosan
FT-IR spectra of samples were studied in 4000-500 cm-1 area with 4 cm-1 imaging potential with
KBr with its pressed mixtures in the AVATAR 370 (Thermo Nicolet Corporation, USA).
Thermogravimetric investigations (TQA, DTA) were held on Thermogravimetric Analyzer (NET-
ZSCH, STA 409 PG.4.G Luxx, USA) in 50 ml min-1 nitrogen environment with temperature rate
100C min-1 from 200C to 4000C. X-ray diffractograms of chitosan and reaction products are outlined
on the German production Bruker Advance D8 equipment. Diffractograms comprised with (2θ)
0.020 imaging scattering rates ranged from 3 to 800, and scanning speeds 2.0 min-1, accelerated
tension 40 kV and intensity 35 mA. Elemental analysis was checked on Elemental Analyzer
(GmbH, Hanau, Germany) at 600C for dry samples. The morphological surface images of chitosan,
intermediate and final product were obtained by scanning electron microscope (SEM, JSM-6390,
Japan). 1H and 13C NMR spectra of initial polymer, intermediate and final product were outlined at
300.13 MHz and 75.47 MHz 300K on the Bruker Avance 300. Deuteriumized D2O and d-acetate
acid were used as solvent . The concentration of samples were taken in the range of 10-25 mg/ml.
The UV- Visible analysis of the samples was carried out using UV- Visible Spectrophotometer
(Perkin Elemr Lamda-850) the absorbance mode in the wavelength choice of 200-800nm.
3. Results and Discussion
The exchange of hydrogen atoms from 85-90% free NH2 groups on the content of chitosan is
commonly found to be substituted by various alkyl and aromatic radicals based on the Schiff
Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39 79
reaction [20-23]. In most cases alkylation and quaternization occur with the addition of the same
radicals. Also, the degree of alkylation of the amine groups and the degree of quaternizatoin
ultimately affect the product's solubility and biological properties, which is explained in various
ways by the researchers [24,25]. Initially, the ethylation process for both protons of amine groups
was done in our study. Based on FT-IR, NMR, elemental analysis and electron spectra
investigations of chitosan, intermediate and final product, the reaction occurs on the following
mechanism:
The presence of a chromophore group in the final product shows itself in the color of the substance
as well as in the formation of a characteristic stripe of the -HC=N+H- double bond in the spectrum
of 1640 cm-1. The peak which belongs to this strip is not observed in the spectrum of chitosan. After
a certain period of time, the change in the color of the solution depends on the following
equilibrium process.
O
N
HO
H2C
OH
O
*
*
CH
Hn
O
NH
HO
H2C
OH
O
*
*
CH
n
CH3CH3
Based on spectroscopic analysis of intermediate products, first monoethylation, then in the
following stage diethylation occur. Depending on the mole ratio of the reaction components,
concentration and nature of aldehyde, the average molecular weight of the chitosan and the reaction
time the gel formation occurs in different forms [26,27]. Synthesis of intermediate and final
products during the reaction is clearly visible in the visual images obtained during the synthesis
process.
Chitosan (powder) Chitosan (2%) and acetate aldehyde,
t=0
t=4 hours t=24 hours t=96 hours t=5 days
Figure 1. The colar changed in the reaction chitosan with acetaldehyde in different time periods
After obtaining the N-ethyl chitosan, the next stage is formation process of N-diethyl chitosan.
-H2O
O
N
HO
H2C
OH
O
*
*
CH
Hn
CH3
O
NH2
HO
H2C
OH
O
*
*
+
H3CC
H
OH+
30 min, T=20
0
C, Str
O
N
HO
H2C
OH
O
*
*
CH
CH3
OH
HH
nn
80 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
As a result of the protonation of the last product with reductant, carbocations are hydrogenated and
converted to N-diethyl chitosan. The reaction equation is as follows.
After synthesis of N,N-diethyl chitosan, quaternized ammonium salt of chitosan is obtained from
the reaction of the product with methyl iodine.
CH
3
J, Asetonitr il
35
0
C, 30 saat
O
N
HO
H
2
C
OH
O
*
H
2
CCH
2
CH
3
CH
3
n
O
N
HO
H
2
C
OH
O
*
H
2
CCH
2
CH
3
CH
3
nCH
3
J
In the last stage, in the situation of the mixting all day with 10% NaCl solution N,N-diethyl,N-
methyl chitosan chloride ammonium salt were obtained.
O
N
HO
H
2
C
OH
O
*
H
2
CCH
2
CH
3
CH
3
n
CH
3
J
NaCl, 20
0
C, 24 saat
-NaJ
O
N
HO
H
2
C
OH
O
*
H
2
C CH
2
CH
3
CH
3
n
CH
3
Cl
After alkylation, FT-IR spectra of product and initial polymer were investigated comparatively. The
absorption strips belonging to the polysaccharide groups in the spectrum of the chitosan and N-
diethyl chitosan groups (C-O-C vibration of asymmetric stretching) in 1157 cm-1, the strips
characterizing II and I alcohol groups 1422 cm-1 and 1378 cm-1, as well as 1087 and 1032 cm-1 bond
strips (the deformation of C-O bond), are the same [28,29]. This shows that, there is not any
chemical changes that have occurred in these groups.
Figure 2. The FT-IR spectrum of Chitosan, chitosan carbocation and N,N-diethyl N-methyl
chitosan iodine.
H
3
CC
H
OH
+
30 min, T=20
0
C, Str
O
NH
HO
H2C
OH
O
*
*
CH
n
CH3
-H
2
O
O
N
HO
H
2
C
OH
O
*
HC CH
CH
3
CH
3
O
N
HO
H
2
C
OH
O
*
HC CH
CH
3
CH
3
- BH3
NaBH
4
,1,5 hr. pH=5.5-10
O
N
HO
H2C
OH
O
*
H2CCH2
CH3CH3
n
Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39 81
The peaks at 1657 cm-1 (assigned to the axial stretching of >C=O bonds of the acetamide groups,
referred to as amide I band), 1571 cm-1 (angular deformation of the -NH2 group), 1260 cm-1
(bending vibration of C-N band) match with the chitosan groups involved in the chemical
modification. The observed peaks in the 3478 cm-1 region belong to tightened vibrations of -OH and
-NH2 groups. After diethylation, the peaks 1592-1598 cm-1 belonging to adsorption strip of the N-H
bond disappeared, which proves the exchange of protons as a result of alkylation. Additionally,
intensive peaks in the 2875 and 1457 cm-1 region are increasing as compared to chitosan, which
corresponds to the asymmetric stretch of C-H bond.
The reaction mechanism was studied based on the molecular structure of chitosan, intermediate
product, basic chitosan derivatives, and also the formation and loss of the chromophore group, the
analysis by the UV-Vis electron spectra was performed. It was determined besides the chitosan, the
intermediate product and the reduced chitosan derivatives were very poorly soluble in water. High
sensitive method has been used in the discovery of the molecular structure of these polymer
modifications. The analysis of samples has been studied in the ultraviolet region due to slight
solubility. Taking this into account, their solutions were prepared (0.01-0.001%) and electron
spectra of them were monitored (Figure 3).
Figure 3. The Uv-vis spectrs of chitosan, N,N-diethyil chitosan (before reduction), and N,N-
diethyil chitosan after reduction.
Apparently, in the content of initial polysaccharide-chitosan spectrum a broad peak around 208 nm
was observed, that belongs to the non-deacetylating fragment, that belongs to the carbodiimide
functional group >C=O. With inclusion alkyl - ethyl or diethyl fragment the structural variation
occurs in the polymer chains. This shows itself in the form of a spectrum and in the formation of the
second absorption band in the 260-270 nm region. Thus, the second intensive peak at the high
wavelength is characteristic to the >C=N- chromophore group or n→π* transition in it. The
breakdown of π bond after reduction affects the electron density of the macromolecule and the
characteristic strip of the chromophore group disappears. This proves that the alkylation reaction
occurs consistently, and the intermediate carbocation product forms a major mass during the
reaction. Also, the electron nature of the >C=O group in the deacetylated chitin residue disrupts due
to alkaline substitution occurring in the chitosan macromolecule within or between macromolecules
that affects the nature of the electrostatic interactions. As a result this proves that the characteristic
strip belonging to this passage is exposed to the chemical sliding with bathochromic shift.
The exact molecular structure of the derivatives from the reaction and the presence of the functional
groups were studied using the 1H and 13C NMR spectroscopy. In the following figure, the 1H NMR
spectrum of chitosan and the final products N,N-diethyl, N-methyl chitosan chloride, and the
signals of corresponding peaks are given.
82 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
Figure 4. The 1H NMR spectrum (left) of chitosan and N, N-diethyl N-methyl chitosan (right).
As the reaction proceeds gradually, NMR spectra of intermediate products were analyzed and
signals of protons and carbons which exposed to basic chemical shifts were registered.
The 1H NMR spectrum of chitosan: (300 MHz, D2O/dacetic acid)
δ 2.08 ppm (-NH2), δ 2.12 ppm (C6-OH), δ 1.98 ppm (C3-OH), δ 4.81 ppm
(H-1) the hydrogen of the 1st carbon in the cycle, δ 3.18 ppm (H-2),
δ 3.79 ppm (H-3), δ 3.2 8 ppm (H-4), δ 4.06 ppm (H-5), δ 3.63 ppm (-CH2-
the protons in the C-6). The 13C NMR spectrum: (300 MHz, D2O/d-acetic
acid) β C-1 δ 102.3 ppm, C-2 δ 53.4 ppm, C-3 δ 68.2 ppm , C-4 δ 72.1 ppm, C-5 δ 72.6 ppm, C-6 δ
59.1 ppm.
N-ethyl chitosan (which C=N band is observed and yellow-brown):
1H NMR spectrum: (300 MHz, D2O/dacetic acid) δ 0.9 ppm (-CH3),
δ 4.87 ppm H-1, δ 2.14 ppm H-2, δ 3.71 ppm H-3.13C NMR spectrum:
-CH3 δ 8.43 ppm, C-1 δ 96.54 ppm, C-3 δ 62.04 ppm
N-ethyl chitosan carbocation (in equilibrium form):
1H NMR spektri: (300 MHz, D2O/dacetic acid) H-1 δ 5.26 ppm, H-2 δ
3.08 ppm, H- 3 δ 3.92 ppm. 13C NMR spectrum: δ 7.4 ppm - CH3, C-1 δ
102.4 ppm, C-2 δ 47.28 ppm, C-3 δ 69.47 ppm,
After protonation, double bond disappears, the substance is discolored, and chromophore groups are
replaced by auxochrome groups. Changes are observed in the common view of the spectrum and in
the chemical shift of signals. Because of the exchange of the proton in the amine group with the
ethyl radical, new chemical signals appear.
The 1H NMR spectrum of N-ethyl chitosan: (300 MHz, D2O/dacetic acid)
-NH- δ 1.98 ppm, δ 2.62 ppm -CH2 I amide, δ 0.98 ppm -CH3, H-2 δ 3.08
ppm, H-3 δ 3.85 ppm and chemical shift in other protons are not sharp. 13C
NMR spectrum: δ 16.37 ppm -CH3, -NH-CH2- δ 40.85 ppm, C-1 δ 99.24
ppm,C-2 δ 57.48 ppm, C-3 δ 66.51 ppm chemical signals in other carbons are
identic to chitosan.
The chemical signals of the methylene in the ethyl group, as well as the signals of carbons in the
methyl group prove that alkylation occurs. When taking aldehyde more than the equimolar ratio (2-
4 times) during the reaction, the alkylation occurs more deeper. Thus, both of the protons in the
amine group are substituted by the ethyl radical, which shows itself in the steps of the process in the
NMR results of the products.
O
NH
2
HO
H
2
C
OH
O
O
*
*
n
1
2
5
4
3
6
O
N
HO
H2C
OH
O
O
*
*
n
1
2
5
4
3
6
CH
H
CH3
O
NH
HO
H
2
C
OH
O
O
*
*
n
1
2
5
4
3
6
CH
2
CH
3
O
NH
HO
H
2
C
OH
O
O
*
*
n
1
2
5
4
3
6
CH
CH
3
Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39 83
The 1H NMR spectrum of N,N-diethyl chitosan (when C=N bond is
observed): (300 MHz, D2O/dacetic acid) δ 1.43 ppm >N+-CH2-,
δ 0.88 ppm CH3, H-1 δ 4.93 ppm, H- 2 δ 1.98 ppm, H-3 δ 3.81 ppm.
13C NMR spectrum: >N+-CH2- δ 4.36 ppm, > N+CH2CH3 δ
10.17 ppm, other methyl group δ 8.31 ppm, C1 δ 95.1 ppm, C-2 δ
66.72 ppm, C-3 δ 59.4 ppm, C-4 δ 73.8 ppm.
The 1H NMR spectrum of N,N-diethyl chitosan: (the equilibrium form
of the carbocation, which is also colorful, and after a while there are some
minor changes in the chemical signals of protons and carbons in the NMR
spectrum by internal grouping) (300 MHz, D2O/dacetic acid): >NCH2δ
2.63 ppm, >N–CH2CH3 δ 1.08 ppm, proton in the methyl group united to
the nitrogen in the carbocation >NCH+CH3 δ 0.91 ppm, H-1 δ 5.11 ppm,
H-2 δ 3.07 ppm, H-3 δ 3.85 ppm. 13C NMR spectrum: >N–CH2δ 35.8 ppm, CH3 δ 17.4 ppm,
>NCH+CH3 δ 5.3 ppm, C–1 δ 100.6 ppm, C-2 δ 48.9 ppm, C-3 δ 67.5 ppm, C-4 δ 73 ppm.
After reductions with NaBH4, the product becomes colourless, it means that the >C=N
chromophore bond is protonated and a new view appears in the 1H and 13C NMR spectrum.
1H NMR spectrum of the main product N,N-diethyl chitosan after
reduction: (300 MHz, D2O/dacetic acid) –N-(CH2)2- δ 2.43 ppm, -
(CH3)2 δ 0.98 ppm, H-1 δ 5.14 ppm, H-2 δ 3.09 ppm, H-3 δ 3.87 ppm.
13C NMR spectrum: -N<(CH2)- δ 44.8 ppm, -(CH3)2 δ 14.2 ppm, C1 δ
98.6 ppm, C-2 δ 57.6 ppm, C-3 δ 64.7 ppm, C-4 δ 73.8 ppm. Other
carbons are not exposed to the chemical shift.
1H NMR spectrum of N,N-diethyl, N-methyl iodine chitosan: (300
MHz, D2O. Bruker ). δ 1.23 ppm >(CH3)2, δ 3.26 ppm >(CH2)2 δ 3.290 ppm
>N+<CH3 , H-1 δ 5.48 ppm, H-2 δ 4.13 ppm, H-3 δ 4.22 ppm. 13C NMR
spectrum: δ 7.8 ppm >(CH3)2 , δ 54.9 ppm >N-(CH2)2-, C-1 δ 90.8 ppm,
C-2 δ 73.6 ppm, C-3 δ 58.4 ppm, C-4 δ 74.1 ppm, >N+-CH3 δ 43.6ppm.
The 1H and 13C NMR spectrum of the N, N-diethyl, N-methyl chloride chitosan remain the same
with the sample containing iodine. The chemicals signals of the proton and carbons are not
mentioned separately because they are close or overlapping. A detailed comparison of NMR results
indicates that alkylation and quaternization of chitosan with acetate aldehyde has been occurred
chemically. Meanwhile, the analysis of intermediate products indicates that the process is
chemically effective.
The thermograms of chitosan and N,N-diethyl chitosan are as follows. The initial thermal change
for the chitosan occurs at 45-50 0C, and for N,N-diethyl and N-methyl chitosan iodine at 80-950C. It
is an indication of water and weight loss in the content. The evaporation and mass loss depends on
the availability of charged areas and number of it in the polymer chain [30]. The second thermal
change occurs at 150 to 260 0C, and this associated with the destruction of the polymer product.
Other latest thermal disruptions - the complete destruction of the polymer, depolymerization and
pyrolysis processes occur at the temperature 350 and above.
O
N
HO
H
2
C
OH
O
O
*
H
2
CCH
CH
3
CH
3
n
1
6
5
4
3
2
O
N
HO
H
2
C
OH
O
O
*
H
2
CCH
CH
3
CH
3
n
1
6
5
4
3
2
O
N
HO
H
2
C
OH
O
O
*
H
2
CCH
2
CH
3
CH
3
n
1
6
5
4
3
2
O
N
HO
H
2
C
OH
O
O
*
H
2
C CH
2
CH
3
CH
3
n
1
6
5
4
3
2
CH
3
J
84 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
Figure 5. Thermogravimetric and differential thermogram chitosan (left) and N,N-diethyl,N-methyl
chitosan iodine (right).
It is known that, some crystalline phase could be observed in the chitosan macromolecule, which is
essentially amorphous. Also, the chemical modification of the polymer macromolecule - the
conjunction of ethyl groups to the content, later, conversion to a salt form affects its crystallinity.
For this purpose, X-ray diffractograms of chitosan and N,N-diethyl chitosan were investigated and
the results were given in the following figure.
Figure 6. X-ray diffractogram of chitosan and N, N-diethyl, N-methyl chitosan iodine.
The two diffraction peaks at 2θ=100 and 19.70 levels for the chitosan characterized by the crystal
domains are shown in the figure. Which, these crystalline phases have been formed due to the
hydrogen bonds between amine groups. In N,N-diethyl N-methyl chitosan iodine (or chlorine)
diffractogram, the peaks are clearly visible, and this indicates that it is in salt form and
crystallization occurs. Also, absence of characteristic peaks for hydrogen bond proves that the
protons in amine group were exposed to the alkylation [31].
According to the results of the elemental analysis, the percentage of C, H, N and halogen in the
product after alkylation is given in the following table. In general, as a result of the alkylation, there
was no change in the amount of nitrogen in the composition, while the carbon decreased and slight
increase are occurred in the hydrogen content. The results of the elemental analysis also show that
the reaction occurs gradually and prove that the alkylation reaction is going on.
Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39 85
Table 1. Elemental component analysis of products.
Polymer samples
Analaysis of (%) C, H, N, J, Cl
theoretically calculated
observed
C
H
N
O
J
Cl
C
H
N
O
J
Cl
chitosan
48.62
7.36
8.89
32.74
-
-
51.64
9.34
16.35
31.87
-
-
N,N-diethyl chitosan
55.74
10.12
6.54
29.58
-
-
47.58
11.69
16.83
32.23
-
-
N,N-diethyl N-methyl
chitosan iodine
57.86
11.28
6.27
27.69
6.37
-
53.78
10.29
6.94
29.48
5.46
-
N,N-diethyl, N-methyl
chitosan chloride
56.18
10.57
5.84
28.47
0.01
5.68
53.82
11.38
6.17
30.38
0.16
7.52
SEM images show surface morphology of ammonium salt of chitosan after the alkylation and neat.
Figure 7. Surface images obtained by SEM for chitosan (left) and N,N-diethyl, N-methyl chitosan
iodine (right).
According to SEM images, the surface of the chitosan is more smooth compared to the product. The
breakdown of the surface structure after alkylation results in formation of non-coincidental zones
[32]. This proves that chitosan is incurred to modification.
N,N-diethyl N-methyl chloride chitosan has the ability to dissolve in water and in a certain pH
range, in contrast to the free polymer. Whereas the solubility of the chitosan is made up 2-3%, its
quaternized chloride ammonium salt has a solubility of 85-88%. Also, chitosan is well-soluble in
the pH=1-5 range, and precipitates in pH=8-12. In the obtained product the functional groups
produce intensive absorption in the solution, which are soluble in pH=1-12 range. The degree of
solubility depends on the amount of aldehyde during the reaction and the content of the
quaternizing reagent methyl iodine [33]. It has been found that the best solubility of N,N-diethyl, N-
methyl chloride chitosan is optimum, when the content of chlorine is 7-8%. Quaternization with
methyl iodine (or chlorine) in more quantities may cause changes in the properties of chitosan,
which is not desirable. Spectroscopic and thermal analyzes show that after quaternization, the
product maintains its basic physical and biological properties characteristic to the chitosan. This
allows it to be used in the process of delivery and controlled release of some antibiotics and
proteins.
Conclusions
Initially, the alkylation reaction of the chitosan with ethanal, then the quaternization with methyl
iodine were investigated, and the mechanism of the process was determined, and the structure of the
product was confirmed with 1H NMR method. The content of the products is determined by
elemental analysis, and surface morphology by SEM. It is shown that, the alkylation on Schiff
reaction passes through the intermediate product phase which has double bond.
86 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
Acknowledgement
The presented work is funded by the Science Development Fund under the President of the
Republic of Azerbaijan on the project - number EIF-KETPL-2-2015-1(25)-56/22/4 "Synthesis of
new hydrophobic and biocide polymers containing nitrogen and oxygen in the content for
immobilization of medicines ".
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88 Journal of Biomimetics, Biomaterials and Biomedical Engineering Vol. 39
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