Polyoleins Journal, Vol. 4, No. 1 (2017)
DOI: 10.22063/poj.2016.1354
ORIGINAL PAPER
IPPI
Two novel methods for synthesizing poly (propylene
fumarate): Technical aspects and role of vacuum and N2
purging effects
Sara Shahbazi1, Yaser Jafari2, Fathollah Moztarzadeh1, Gity Mir Mohammad Sadeghi3*
1
Department of Medical Engineering, Amirkabir University of Technology, Tehran, Iran
Department of Analytical Chemistry, Faculty of Chemistry, University of Kashan, Kashan, Iran
3
Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box: 158754413, Tehran, Iran
2
Received: 12 March 2016, Accepted: 29 May 2016
ABSTRACT
Poly (propylene fumarate) (PPF), a linear unsaturated polyester consisting of alternating propylene glycol and fumaric
acid units, can be cured in vivo to ill the skeletal defects with minimal surgical intervention. Many different methods
have been reported for synthesizing PPF, but none of them gives a clear method. The present paper introduces two new
methods in PPF synthesis: Modiied relux system (MRS) and mixed relux-distillation system (MRDS). Similarly,
the effects of applying vacuum (vacuum sequence, time, vacuum applying position, and the distance between vacuum
applying position and reactor) as well as nitrogen gas (used continuously or only as an N2 blanket) on the PPF synthesis
have been studied. The PPF obtained using optimum reaction condition has been characterized by using NMR, FTIR,
and GPC analyses. It is demonstrated that the eficiency of MRDS in synthesizing PPF is higher than that of MRS.
Nitrogen gas, vacuum applying position, continuously/stepwise-continuously applying vacuum and other parameters
show an important role in the polymerization of PPF in both the MRDS and MRS systems. Polyoleins J (2017) 4:
27-41
Keywords: Poly (propylene fumarate); modiied relux system; mixed relux-distillation system.
INTRODUCTION
These days, biodegradable materials are becoming
popular in packaging, agriculture, medicine, and other
areas. The biodegradable unsaturated polyesters, due to
their ability to be cross-linked in situ and to degrade
gradually, are the most promising materials in the
tissue engineering ield [1]. Due to slow hydrolysis,
polyesters are the most common degradable synthetic
polymers used in tissue engineering applications. For
example, polyesters such as poly (L-lactic acid) and
poly (D, L-lactic-co-glycolic acid) are biocompatible
* Corresponding Author - E-mail: gsadeghi@aut.ac.ir
and biodegradable materials that can form scaffolds for
in-situ tissue engineering applications [2, 3].
Poly(propylene fumarate) (PPF) as one of the most
important biodegradable polymers is a linear unsaturated
polyester consisting of alternating propylene glycol
and fumaric acid units [4]. The main advantage of the
unsaturated polymers is their ability to cure in vivo;
thereby the possible skeletal defects in any shapes or
sizes will be illed with minimal surgical intervention.
PPF has the inherent advantage of fumarate units that
allow the polymer chains to be covalently cross-linked
through its carbon-carbon double bonds with relatively
Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
low levels of heat release [5, 6].
Thus, PPF can be fabricated in situ to obtain a threedimensional scaffold. The molecular weight of linear
PPF affects the mechanical and degradation properties
of cross-linked composites that will be used in the
orthopedic applications [2, 5-10]. In order to synthesize
PPF with a reproducible molecular weight and to
control the polymer synthesis, many different methods
have been reported [7-13] that these routes have been
associated with signiicant by-product formation.
As shown in Figure 1, a common method for
synthesizing PPF follows a two-step procedure,
beginning with diethyl fumarate and propylene
glycol reaction, and involving bis(hydroxypropyl
fumarate) as an intermediate. More recently,
procedure formulations of PPF synthesis were adapted
frequently based on Shung et al. studies [13]. In brief,
diethyl fumarate is reacted with propylene glycol in
a three-necked round bottom lask at a molar ratio of
1:3. Hydroquinone, a crosslinking inhibitor, and zinc
chloride as the reaction catalyst are added to the lask
containing diethyl fumarate with ratios of 0.003 and
Figure 1. Reaction scheme for the step polymerization of
poly (propylene fumarate) from propylene glycol and diethyl
fumarate.
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0.01, respectively. Moreover, the other techniques of
PPF synthesis have been reported as follows:
According to a research conducted by Hakimimehr
et al. [14], PPF is synthesized in a Vigreux distilling
column attached to the reactor kept under nitrogen
while stirring. The reactor is then submerged in an
oil bath and the temperature is increased to 140°C
over a period of 1h. Upon the removal of 90% of the
theoretical ethanol from the system as a distillate, the
reactor is cooled down to 100°C and placed under
vacuum.Temperature is then slowly increased at a
rate of 10°C/15 min to 140°C. At this step, the diester
intermediates react through a self-transesteriication
process and propylene glycol is collected as a distillate.
The molecular weight of the polymer is dependent on
the period of time (12 h) in which the polymer is kept
at the inal temperature 140°C.
In the research done by Temenoff et al. [15], the
reaction runs for approximately 8h in an inert atmosphere
and the temperature gradually increases from 100°C
to 160°C. This reaction produces the intermediate
bis (hydroxypropyl fumarate) as well as ethanol, and
the reactor is heated when 80-100% of the theoretical
ethanol has been collected in a receiving lask. In the
second step, PPF and the by-product propylene glycol
will be produced. This reaction is run for approximately
8 h under vacuum (<1 mmHg) while the temperature is
slowly increased from 90 to 150°C.
The synthesis of PPF presented by Beke et al. [16]
is also reported elsewhere [8]. Briely, fumaric acid is
heated in an excess of propylene glycol at 145°C. A
Barrette trap is connected beneath the condenser and
the water is collected as a by-product. After 3-4 h, the
reaction temperature is increased to 180°C for 2 h to
collect the unreacted propylene glycol.
According to the work carried out by Timmer et al.
[17], the mixture of the reactants is heated to 150°C
under a nitrogen blanket. Reaction continues until
90% of the theoretically expected amount of ethanol,
as a by-product of the reaction, has been distilled. The
reaction then undergoes transesteriication by heating
the vessel to 130°C under vacuum (1 mmHg).
Polypropylene fumarate is also prepared by
condensation through reluxing using a condenser at a
high temperature (200°C) and vacuum conditions for 2
h [18].
Many different methods have been reported for
synthesizing PPF, but none of them gives a clear
method. The references 13-18 represent some of PPF
synthesizing procedures reported until now. In these
papers, PPF synthesis is not reported in detail. In the
Polyoleins Journal, Vol. 4, No. 1 (2017)
Shahbazi S. et al.
other word, one or several key points in the synthesis of
PPF may be ignored or the procedures are not clearly
presented in detail, therefore these shortages can
inluence on the reproducibility of PPF synthesis. For
example, in references 14, 15, and 17 it is said that the
reaction will continue to remove 80-90% of amount
of theoretically expected by-products (ethanol, water
or propylene glycol) from the system as a distillate,
but none of them gives a good solution for reaching
this situation. Thus, there are some dificulties with
the control of polymer molecular structure. In fact, the
purpose of this study is to guide and help researchers
who want to know how to synthesize this material
with high reliability and reproducibility.
After some experiments on PPF synthesis in our
studies, the present paper describes two new methods
of synthesizing PPF called modiied relux system
(MRS) and mixed relux-distillation system (MRDS).
The latter provides a high eficient synthesis procedure
which is our inal target. MRSD overcomes most
problems associated with PPF synthesis that MRS
and other reported techniques are encountered. This
method which is a mixed relux system is coupled with
a simple distillation system to allow synthesizing PPF
eficiently. Likewise, the effects of applied vacuum
(vacuum sequence, time and vacuum position, and
vacuum applying position-reactor distance) and type
of applying nitrogen gas used (continuously or only an
N2 blanket) on PPF synthesis in MRS and MRDS have
been studied. According to FTIR analysis, the bestsynthesis system and conditions for the preparation of
PPF have been introduced. Furthermore, the polymer
composition of the PPF obtained using the best
synthesizing system (MRDS) has been investigated by
using NMR and FTIR spectroscopies. Gel permeation
chromatography (GPC) has been employed to
determine the molecular weight distribution of PPF.
EXPERIMENTAL
Materials
Diethyl fumarate (DEF), propylene glycol (PG), zinc
chloride (ZnCl2), methylene chloride and hydrochloric
acid were the reagent-grade and purchased from Merck
and hydroquinone was obtained from Sigma-Aldrich.
Synthesis of polypropylene fumarate
Diethyl fumarate was reacted with propylene glycol
in a three-necked round bottom lask (reactor) at a
Polyoleins Journal, Vol. 4, No. 1 (2017)
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ratio of 1:3.5. Hydroquinone, a crosslinking inhibitor,
and zinc chloride as the reaction catalyst and diethyl
fumarate were added to the reactor with a molar ratio
of 0.002 and 0.01, respectively. For PPF synthesis, each
of modiied relux system (MRS) and mixed reluxdistillation system (MRDS) was used separately. MRS
is a simply designed relux setup that was equipped
with an Erlenmeyer trap for the collection of byproducts. Also, MRDS which is more complex than
MRS consists of both relux and distillation setups. The
type of applied relux condenser in MDRS is different
than the simple condenser used in MRS. MRDS which
is equipped with a distillation system is proposed to
provide an optimized collection of by-products.
It should be noted that all conditions applied
for polymer synthesis were kept constant for both
the systems except differences in type of applying
nitrogen gas (continuously or only at an N2 blanket)
and manner of vacuum applied (time and sequence
of the applied vacuum and vacuum-reactor distance)
in several batches. The details of these systems and
their utilization in the PPF synthesis procedure are
completely discussed in the results and discussion.
However, the reactants depending on the type of the
applied system, were purged by continuous nitrogen
low (in MRDS) and non-continuous nitrogen low
(in MRS) in a reactor that was submerged in an oil
bath, and magnetically mixed using a stirrer. The
temperature was increased to 120°C over a period of
1h.
In the irst step, bis (hydroxypropyl fumarate)
was produced as an intermediate. The reaction
performance in this step was different for each system.
At the beginning of the second step (after 4 h from the
start of reaction), the reactor of diesters was cooled
down to 90°C and then placed under vacuum (400
Pa). The applied vacuum in one batch was continues
(MRDS) and in another batch was stepwise (MRS)
(5 min vacuum every 30 min from starting time of
the cycle of applying vacuum). The temperature
was then slowly increased to 140°C (10°C/15 min)
and then the reaction continued at this temperature.
Diester intermediates were run through a selftransesteriication process and propylene glycol was
collected as a distillate. The molecular weight of the
polymer depended on the period that the polymer was
kept at the inal temperature.
The PPF was prepared by keeping the temperature
constant to 140°C for 10 h [14]. Finally, the reactor
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Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
was cooled up to room temperature under a purge of
nitrogen. When the desired PPF molecular weight
was achieved, it could be detected by reduction in OH
groups signals in FTIR spectrum.
Consequently, the reaction product was dissolved
in methylene chloride, and then washed with 5%
aqueous HCl to remove the unreacted monomers and
ZnCl2. Afterward, it was puriied by washing with pure
water and brine. Sodium sulfate was used as a drying
agent for the organic phase. Concentrated product was
then precipitated in ethyl ether twice to remove the
inhibitor. Finally, the remained solvents were removed
from PPF by vacuum-drying at 60-70°C during 24 h.
The puriied resin was highly viscose and light brown.
The obtained resin was characterized by FTIR and H
NMR analyses. The molecular weight of PPF was also
determined by GPC.
Chemical and physical characterization
Fourier transforms infrared spectrometry (FTIR)
FTIR spectra were obtained by a BOMEM SPG5800G
FTIR spectrometer. The characteristic peaks at 1726
cm-1 belongs to the ester linkages, 1646 cm-1 due to
a vinyl moiety, 1455 and 1375 cm-1 correspondence
to the methyl stretching and at 1296 cm-1 belongs
to a secondary alcohol can be observed in the FTIR
spectrum of PPF shown in Table 1 [19].
Nuclear magnetic resonance spectrometry (NMR)
H NMR spectra were obtained using a Bruker Avance
400 MHz NMR system (Bruker Analytik GmbH,
Rheinstetten, Germany) operated with a Silicon
Graphics O2 workstation (Silicon Graphics, Mountain
View, CA). Proton spectra were obtained using a 30°
pulse angle, 4s acquisition time, and 3s delay time. The
samples were run in CDCl3 using TMS as a reference.
Gel permeation chromatography (GPC)
The molecular weights of the synthesized PPF were
determined by a gel permeation chromatography
system (model: GPC Agilent 1100) equipped with
Table1. Wavenumbers of bands in PPF [19]
Bands (cm–1)
Assignments
3446
2960
1730
OH groups
Stretching frequency of CH2
Stretching frequency of acid and ester
carbonyl group
Unsaturation C=C in fumarate unit
C–O stretching vibrations
1643
1000–1300
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a chromatography column (Agilent & PL gel, 3 m,
300×7.5 mm column, 50- 100,000 DA range), and a
refractometer index detector. THF as a solvent with
a low rate of 1ml/min was used. Molecular weights
were determined using a calibration curve generated
according to ASTM D6579-11.
RESULTS
Both the MRS and MRDS systems were used and
compared in some points of view. The product obtained
using each system was characterized and the effective
parameters of the synthesis reaction were evaluated.
Synthesis of PPF by both the methods required
careful implementation of polymerization conditions.
The molecular weight of PPF increased during polyesteriication and trans-esteriication procedures at
the temperatures about 130-140°C. The reaction time
was 14 h and 17 h for MRS and MRDS, respectively.
In the second step, vacuum was necessary for both
the methods. The chemical structures of products
were studied using FTIR. Reduction in absorption of
terminal hydroxyl groups in the region of 3300 cm-1,
was used to evaluate polymerization progress. Finally,
NMR and GPC were used to characterize the best
product.
Modiied relux system (MRS)
This system was equipped with an Allihn condenser
and an Erlenmeyer as a trap (Erlenmeyer-trap) which
cooled with an ice-water bath to condense hot vapors.
The Erlenmeyer-trap was connected to one of the
reactor-openings (see Figure 2 (a)) to collect byproducts. By-products consisted of ethanol produced
in the irst step and excess propylene glycol produced
in the second step of the PPF synthesis reaction. At
irst, reactants including diethyl fumarate (DEF),
propylene glycol (PG), zinc chloride and hydroquinone
with the molar ratio of 1:3.5:0.01:0.002 were added
to a tree-necked reactor. The reactor was placed on a
stirrer and equipped with a tube under a continuous N2
low at a rate of 5 bubbles/second. The temperature
was increased to 120°C in 1 h; then, the reaction
continued at this constant temperature. After 30 min,
the temperature was increased to 140°C at a rate of
5°C/min; 2.5 h after starting the reaction a frothy
material was observed in the reactor, resulting from
passing ethanol as a by-product through the monomers
Polyoleins Journal, Vol. 4, No. 1 (2017)
Shahbazi S. et al.
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Figure 2. (a): Modiied relux system (MRS). (b): Mixed relux-distillation system (MRDS).
MRS: 1-Injection needle, 2- Allihn condenser, 3- commun tube, 4- Erlenmeyer-trap, 5- N2-inlet, 6-Vacuum applying tube,
7- Reactor, 8- Stirrer, 9-Lab magnet, 10-Thermometer
MRDS: 1-Glass adaptor, 2-Vigreux condenser, 3- N2-inlet, 4- Reactor, 5-Stirrer, 6- Lab magent, 7- Thermometer, 8-Leibig
condenser, 9-Glass vacuum adaptor, 10-Vacuum tube, 11- Received lask, 12-N2-outlet, 13- lab jack
and dimers in the reactor. Then the temperature was
decreased to 80-90°C rapidly (10°C/min). Just in this
moment, continuous N2 inlet valve was closed and
the mixture in the reactor was maintained under N2
blanket at this temperature for 30 min.
The amount of the by-product in the irst-step of
the reaction remained in the Erlenmeyer-trap was
about %75 of theoretical ethanol. Then, N2 gas was
entered continuously similar to the initial stage of the
reaction. The temperature was risen up to 140°C at
a rate of 5°C/min and the reaction continued at this
temperature. Again, after 1h, all above steps were
repeated for three times one by one (with intervals of
1h). This step was achieved during 6-7 h. Then, the
vacuum tube was replaced with the N2 tube. In the
second step, the applied vacuum (400 Pa for 5 min
at 140°C) caused boiling of PG, removing PG vapors
from the reactor and developing the reaction. A 30
min interval was used for applying vacuum, 10°C
temperature increase and applying vacuum for 5
min. This step was lasted for 6-7 h (10 times vacuum
applying for 5 min, every 30 min).
In this step, increasing temperature to 165°C would
cause decomposition of oligomers in the reactor.
Afterward, the reactor was cooled to the room
Polyoleins Journal, Vol. 4, No. 1 (2017)
temperature under an N2 blanket. Finally, the product
was washed and puriied. Figure 3 (a) shows the FTIR
of distilled ethanol in the irst step; and the by-product
of the second step (propylene glycol) is seen in Figure
3 (c). In this reaction, the amounts of PG and ethanol
collected in the both steps were 22% of the initial
amounts of PG and DEF by volume. After collecting
by-products, the reaction inished and continuing
the reaction led to produce a solid-like material. In
general, the product of this system was a high viscous
and dark-yellow clear material. Figure 4 (c) shows the
FTIR of the PPF obtained using MRS.
Figure 3. (a): FTIR of ethanol (as a by-product): sampling
from the vapor phase of the reactor in MRS. (b): FTIR of
propylene glycol (as a by-product) from MRDS. (c): FTIR of
propylene glycol (as a by-product) from MRS.
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Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
Figure 4.
column is
fumarate)
fumarate)
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differences as follows:
(Note: In the whole of the text, the mixture term
refers to all reactants, by-products, intermediate,
catalyst and inhibitor that exist in the reactor).
1. The reaction continues under continuous purging of
N2 until the irst step inishes (about 6h).
2. There is not any ethanol in the irst step.
3. The vacuum must be applied stepwise for 8h after
starting of the second step.
In this system, the amount of collected propylene
glycol in the reactor was 21% of the initial amount
of PG and DEF by volume. After 17h, the reaction
was inished and continuing the reaction led to the
formation of a high-viscous material. In general, the
product obtained by using this system was a highbrown and clear material with a higher viscosity than
that obtained by the MRS. Figure 3 (b) shows the
distilled PG as a by-product which was obtained in the
second step. In addition, the FTIR of the PPF obtained
by the MRDS is shown in Figure 4 (b).
(a): FTIR spectrum of the product when Vigreux
not used. (b): FTIR spectrum of poly (propylene
in MRDS. (c): FTIR spectrum of poly (propylene
in MRS.
Mixed relux-distillation system (MRDS)
In this method, a simple distillation apparatus was
modiied by inserting a Vigreux condenser between
the reactor and Liebig condenser head. Volatile
compounds such as ethanol in the irst step and PG
in the second step were heated to boil the mixture.
Then, the generated vapors were cooled and liqueied
by several passing through a Liebig water-cooled
condenser and collected in a separate container, called
the receiver lask (see Figure 2 (b)). All steps were
similar to those in the MRS procedure, but with some
Chemical and physical characterization
FTIR results of MRDS and MRS
The infrared spectra of synthesized PPF by MRDS
Table 2. Effects of production parameters on properties of the products based on primary studies (MRS and MRDS)
Number
DEF/PG
(h) Time
Temperature
(°C)
Vacuum applying
Properties of obtained product
FTIR
1
1:1.5
1:2.5
1:3.5
1:4
7.5*
9*
10
13
140
140
140
140
-
A Light brown substance similar to a hard ball
Light brown- high viscosity
Light brown-middle viscosity
Light brown- middle viscosity
a
b
c
d
1:3.5
1:3.5
1:3.5
3
8
2 phase-12
140
140
140
Light yellow liquid
Dark yellow liquid
Light brown- middle viscosity
a
b
c
1:3.5
2 phase-17
140
Stepwise over
phase 2
Stepwise over
phase 2
Light brown- high viscosity
d
1:3.5
1:3.5
1:3.5
1:3.5
20.. 2 phase2 phase-14
2 phase-12*
3.5*
90
120
160
190
Stepwise
Stepwise
-
Light brown- middle viscosity
Light brown-relatively- high viscosity
A dark brown solid - very pungent smell
A light brown solid foam- very pungent smell
a
b
c
d
1:3.5
2*
140
A dark yellow solid
a
1:3.5
2 phase- 10*
140
A light brown gel
b
1:3.5
2 phase- 14
140
Bright red- middle viscosity
c
1:3.5
2 phase-14
140
Continuous at the
irst step
**StepwiseContinuous
Stepwise over
phase 2
Stepwise over
phase 2
Dark brown- high viscosity
d***
2
3
4
*The reaction during stated time will have been spontaneously stopped with producing a solid or highly viscous material.
**Stepwise applying vacuum in the irst step of the reaction and applying continuously in the second step.
***d and c in number 4 are related to MRS which was performed by the same procedure, but the obtained products are not similar (Lack of reproducibility).
32
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Figure 5. FTIR spectra of obtained products from different experiments (by various setups) according to earlier reported
methods, MRDS, and MRS (numbers 1-4 each are related to changing a parameter).
and MRS are presented in Figure 4.
Comparison of some effective parameters in
synthesizing PPF by primary studies
There are numerous different parameters in the PPF
synthesis procedures that can inluence the properties
of the inal products such as molecular weight, the
number of conjugated bonds (crosslinking density),
the amount of by-product entrapped into the polymer
chains, viscosity and etc. We have presented the data
in the Table 2 and Figure 5 (corresponding to the
Table 2) indicating the results of our experiments
Polyoleins Journal, Vol. 4, No. 1 (2017)
(by various setups), according to the reported earlier
methods, MRDS and MRS. The table and igure make
easier evaluation of some parameters such as time,
temperature, vacuum applying and the molar ratio of
monomers on the properties of the products.
H-NMR result for MRDS
The H-NMR spectrum of the PPF synthesized by
MRDS is represented in Figure 6.
GPC for MRDS
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Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
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however, increasing the temperature had a contrasting
effect and caused to change the composition of the
condensed liquid, (leading to higher percentages of
PG and DEF). Thus, modiication of Allihn condenser
with Erlenmeyer-trap led to the system being like a
simple distillation. Repeated reluxing cycles resulted
in the development of polymerization in MRS.
In general, the mentioned method is a complex and
low eficient method for producing PPF. In the irst
step, controlling temperature increase or deacrese
is dificult during N2 purging. But, this method is
suitable for producing materials such as polyurethanes
that their synthesis reactions do not have by-products.
MRS is not an eficient method for synthesizing PPF.
Figure 6. 1HNMR (400 MHz, CDCl3, ambient temperature)
spectrum of PPF
The GPC chromatogram shows that the PPF
synthesized by MRDS has an Mn of 1167 gr/mol, Mw
of 2195 g/mol and PDI of 2.8 (Figure 7).
DISCUSSION
Technical and experimental evaluation of the
systems
Modiied relux system (MRS)
Relux was used to save the energy required for
continuing the synthesis reactions over an extended
period of time. In this method, an Allihn condenser
was connected to the reactor to recycle back vapors
of PG and DEF to the mixture after cooling, and
relux them to the reaction vessel. The reactor was
then heated vigorously during the reaction. Ethanol
boils at about 70-80°C. Flowing N2 gas in the reaction
exits through the attached needle on top of the Allihn
condenser after entering the reactor through a tube
which is connected entering nitrogen to Erlenmeyertrap. The analysis of the composition of collected
vapors from upper reactants of the reactor at 90°C
(that it condenses to liquid) shows that the majority
of the collected vapor is ethanol and the contribution
of vapor of PG or DEF (monomer) is minor. In fact,
the vapors on the upper phase of the mixture are more
volatile components. The upper phase composition is
being controlled by Raoult’s law as described in the
reference [20]:
The vapor was enriched in ethanol (90-95%),
34
Mixed relux-distillation system (MRDS)
Distillation is a widely used technique for separating
compounds based on differences in their boiling points.
Many organic compounds are relatively volatile, i.e.
they have high vapor pressures and low boiling points.
Thus, combining a distillation system with a relux
system can be very suitable for reluxing reactants
and separating ethanol/excess PG by-products from
the reactor mixture in PPF synthesis. After running
the irst step for 6h, the intermediate diester, bis
(hydroxypropyl fumarate), reacted through transesteriication and produced the inal PPF. Propylene
glycol was produced in this step as a by-product and
collected by the cooling condenser (Liebig).
In addition, PG acted as a solvent in the irst step.
Therefore, distillation caused to remove the excess
solvent in the irst step. When the mixture of PG
and synthesized oligomers, obtained from the irst
step, was heated, the temperature raised up to the
temperature of substance with lowest boiling point
(PG) in the mixture, While, the other components
in the mixture, oligomers, remained in the liquid
phase. MRDS is based on a numerous performance
vaporization-condensation cycles by Vigreux
condenser before reaching vapors to Liebig condenser.
Each vaporization-condensation cycle is equivalent to
a simple distillation, in which vapors reach the top of
the Vigreux condenser continuously; it has undergone
similarly to several simple distillations (Figure 2 (b)).
Hot vapors of PG passed through Liebig condenser
and converted to a liquid which was then collected in
the receiver lask. These vapors and inal distillates
contained a high percentage of the PG (liquid with a
lower boiling point) that is shown in Figure 3 (b). If the
Polyoleins Journal, Vol. 4, No. 1 (2017)
Shahbazi S. et al.
condensation-vaporization cycle repeats suficiently
many times, vapors of PG will be converted to a pure
material and the PG obtained from MRDS will be
purer than that obtained from MRS.
At the same time, the synthesized oligomers
(less volatile compounds) are enriched in the other
direction. As the condensed oligomers fall down to
the reactor, the reactor mixture will contain a higher
percentage of the less volatile compound, gradually.
The Vigreux condenser must be positioned vertically
because of the condensed oligomers can fall down
across rising hot vapors to the reactor. This percolation
promotes the equilibrium between liquid and vapor
phases, conditions that allow processing to operate
at the maximum eficiency and provide the optimum
separation of PG and oligomers. Thus, the position of
condenser has an effective role in the polymerization.
After above-mentioned steps, recycling oligomers
as well as separation of pure PG at 140°C, reaction
continued in the reactor in the presence of a catalyst.
Therefore, this system is very eficient for puriied
separation of oligomers and PG. If the received vapors
are cooled by Liebig’s condenser, PG vapors will be
collected in the receiver lask more eficiently. This is
proved that it is pure PG and its FTIR spectra is similar
to the FTIR spectra of INDEX pure PG as shown in
Figure 3 (b). Similarly, the presence of oligomers (less
volatiles) in the reactor leads to polymerization of
oligomers in the presence of a catalyst.
Oligomers (high-boiling compounds) will vaporize
only if heat is increased continuously. If the temperature
is not increased, it is impossible that oligomers relux
in Vigreux condenser, because the evaporation cannot
be taken place. Thus, increasing the temperature of
the reaction up to maximum 140°C is an important
parameter to promote the oligomers condensation.
When Vigreux condenser is not used, the mixture
of distilled PG will not separate completely as shown
in the FTIR spectrum in Figure 4 (a). This problem
is referred to increasing temperature continuously
during the second step. The collected distilled sample
is consists of two components: PG and oligomers of
PPF.
Evaluation of the systems based on the roles of
vacuum and N2 purging in details
Study on effect of thermodynamic parameters on
MRDS and MRS:
Polyoleins Journal, Vol. 4, No. 1 (2017)
IPPI
1) Effect of nitrogen gas as an inert atmosphere
Generally, polymerization reaction takes place under
an inert protective atmosphere of nitrogen. The
inert atmosphere protects against thermo-oxidative
degradation during the reaction. An N2 purging causes
to prevent oxidation, therefore, provides a suitable
condition for maintaining a protective layer of gas
on the top of the mixture constantly. Flowing N2 gas
not only helps to remove by-products vapor but also
prevents discoloration (which would occur in the
presence of oxygen) [10]. Despite this, nitrogen gas
has other roles on polymerization in both systems that
have been described in the following parts of the text.
2) Importance of ethanol extraction in the irst step
Esteriication reaction, as an elementary step of polyesteriication, is an equilibrium reaction.
Therefore, increasing the molecular weight of PPF
is highly depended on the elimination of by-products
from the reactor.
3)Applying vacuum in the irst step
Applying a vacuum for removing ethanol at the
beginning of the reaction led to removing DEF and
PG out of the reactor and changing stoichiometry of
monomers (molar ratio). Thus, the reaction product
did not have a correct molar ratio and its structure was
incomplete in both the systems. Applying a vacuum
in this setup led to producing a high stiff material that
was insoluble in methylene chloride and other organic
solvents. However, it has been said that if ethanol is
initially distilled off very fast under vacuum, it will
facilitate synthesis of polymers [21].
4) Importance of propylene glycol extraction in the
second step
When ethanol removes from the reactor completely,
the polymerization becomes very slow and the second
step of poly-esteriication starts. PG removal from
PPF is more dificult, thus the vacuum needs to be
applied for PG elimination [22].
The pressure in the second step should be decreased to
400 Pa before starting this step (when a large amount of
ethanol is eliminated). The irst important point is that
the stirrer speed should be increased during the reaction
because with increasing the viscosity of material during
the time, removing by-product becomes dificult. If this
condition fulills, the reaction will run smoothly.
5) Importance of applying vacuum in the second step
35
Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
Vapor pressure is a pressure that molecules exert
against external pressure at the surface of liquid which
is usually an atmospheric pressure. The vapor pressure
of a substance roughly doubles for each increase of
10°C. When vapor pressure of reactants mixture
equals to applied pressure, the mixture boils. Thus, the
boiling point of PG is a temperature, in which vapor
pressure equals to applied pressure and evaporation
continues until the equilibrium is achieved between
the molecules entering and leaving reactants mixture.
Note that under vacuum, the boiling point of a mixture
will be lower than its boiling point at an atmospheric
pressure. This can be exempliied by looking at the
boiling point of PG at different pressures since liquid
boils at lower temperatures under vacuum. Vacuum
distillation is used to distil high-boiling mixture of
reactants that would decompose oligomers at their
normal boiling points. Then, if pressure on the liquid
surface is lower than pressure of PG at its boiling
point, it causes to prevent oligomers degradation due
to the fact that lower pressure doesn’t need to a higher
temperature to reach the boiling point of PG.
6) Importance of vacuum applying position
Distance of vacuum applying position from the reactor
is very important in both the systems. The second step
of the reaction should be run under lower pressure and
if the position of vacuum head is inappropriate (for
example the head is very close to the reactor) reactants
or low weight oligomers remove from the reactor and
the stoichiometry of the reactants will be changed.
Therefore, repeatability of the reaction is reduced
dramatically and different products with different
structures may be produced.
7) Applying vacuum: continuously and stepwise
Applying vacuum consistently and stepwise (15
min vacuum-30 min without vacuum) effects on the
product quality. If applying vacuum continues in the
whole of the reaction, polymerization will be stopped
after 2 and 5 h in MRS and MRDS, respectively. In
our experiments, it was found that the best condition
in applying vacuum was an stepwise manner with
the maximum distance of vacuum position from the
reactor. A short distance causes the monomers and
oligomers remove suddenly. Vacuum is used to reduce
the pressure of the system to encourage removing the
by-products. Generally, applying vacuum is a very
important factor in increasing the polymerization
36
IPPI
reaction rate. But, continuously applying vacuum not
only causes the reaction proceeds in an unrepeatable
manner but also gives unreliable results. It was found
that the best condition in applying vacuum was
stepwise consisting of two steps: 5 min vacuum (400
Pa) and 30 min without vacuum repeated for 6 - 8 h.
Modiied relux system (MRS)
Importance of nitrogen gas
In the MRS, if the N2 inlet and evolved gas streams
(ethanol and PG) have a common narrow channel, the
reaction will be controlled via this channel. To run the
reaction continuously, two important parameters with
a critical effect on the operation of the reaction are:
1- Purging N2 gas continuously,
2- Common route between N2 entrance and by-product
collector tube (Figure 2 (a)).
Flowing nitrogen in a stepwise manner in the irst
step led to collection of ethanol as well as the
development of the reaction. When, N2 gas was purged
continuously, the reactants in the condenser underwent
the esteriication reaction to produce frothy material.
At this time, ethanol was at its highest volume and
temperature needed to be reduced to 80-90°C, leading
to reducing the volume of vapors (unless ethanol) to
their minimum volume. Reduction of temperature
before disconnecting of N2 is very important. The
vapors in the Erlenmeyer-trap contained ethanol, DEF
and PG (50% by volume of ethanol, 50% by volume
of DEF and PG).
Condensation at 90°C led to form more ethanol and
less PG as well as DEF collection (85-90% ethanol,
10-15% both PG and DEF). The FTIR spectrum seen
in Figure 3a shows the spectrum of the vapors. But,
Figure 3 (a) shows that some amount of PG and DEF
always evaporate with ethanol in the irst step that
causes changing the stoichiometry ratio and reducing
the eficiency of MRS consequently. Ethanol vapors
condensed by passing through the tube located
between N2 entrance and Erlenmeyer-trap and by
repeating the mentioned steps the amount of obtained
ethanol reached up to 90-95% of its theoretical
amount. N2 purging rate and stepwise applying of N2
are the effective parameters for synthesizing PPF by
MRS.
Importance of vacuum applying position
The role of vacuum applying position in MRS is
to avoid monomer stripping. If the diameter of the
Polyoleins Journal, Vol. 4, No. 1 (2017)
Shahbazi S. et al.
reactor-vacuum connection is very small (about 5
mm) the pressure will be decreased slowly (400 Pa/
min). Therefore, suddenly evaporating monomers/
oligomers can be avoided. Furthermore, the distance
between the vacuum pump and the reactor can be
extended using a narrow long tube to reduce monomer
evaporation.
Role of vacuum
Applying stepwise vacuum in MRS is more
appropriate than applying it continuously. Applying
vacuum dynamically leads to removal of monomers
and lower molecular weight oligomers and can reduce
the reaction time in the second step from 6-8 h to 2 h
(4a, according to Table 2 and Figure 5). Decreasing of
the time causes to incomplete progress of the reaction.
The FTIR spectra of the samples synthesized by MRS
shown in Figure 5 (4c and 4d) demonstrate that most
of terminal OH groups are diminished with applying
the vacuum in the second step. In fact, development
of the reaction strongly depends on the vacuum, and
more importantly the method of applying vacuum.
The products resulted from applying stepwise vacuum
in MRS are not reproducible as shown in Figure 5
((4c) and (4d)) (with similar synthesis conditions but
different spectra). Therefore, it can be concluded that
applying stepwise vacuum in MRS will not lead to a
reproducible production.
Mixed relux-distillation system (MRDS)
Importance of nitrogen
A dry nitrogen gas low is usually enough to remove
ethanol from the reactor. A moderate nitrogen stream
lows through the system and a created nitrogen bubble
in the water illed beaker indicates the rate of ethanol
exiting from the system. However, an excessively
nitrogen lowing rate may result in undesired removal
of volatile reactants such as the diethyl fumarate.
The polymerization eficiency is also corresponded
to nitrogen purging rate directly. If distillation is
conducted very rapidly, liquid-vapor equilibrium will
not be established in the Vigreux condenser, and a
poor separation of by-products will result. Synthesis
of PPF by polyesteriication between DEF and PG is
operated under a moderate inert atmosphere. At the
beginning of the reaction, nitrogen low should be
2 bubbles/second. Afterward, when the most of the
ethanol distils off, in order to remove excess glycol,
the speed of the bubbles production should be fast
Polyoleins Journal, Vol. 4, No. 1 (2017)
IPPI
(5 bubbles/second). Similarly, N2 lowing has an
effective role in transferring PG to the upper part of
the Vigreux condenser.
Ethanol extraction in the irst step
It has been said, ethanol as the irst step reaction
by-product was collected by distillation and the
reaction was run until 90% amount of theoretically
expected ethanol was obtained [13-15, 17]. But, such
phenomenon was not observed in MRDS. Ethanol
is more volatile, therefore its vapors pass through
micro-pores of adaptors rather than accumulation.
While, propylene glycol is driven off and collected as
a distillate during self-transesteriication of diesters
intermediates, bis (2-hydroxypropyl fumarate).
Some amount of ethanol evaporates into the air and
the rest condenses on the inner condenser surface. It is
found that after running distillations in the irst step,
much of the ethanol will be lost. Therefore, ethanol
will not be condensed at all.
Chemical and physical characterization
FTIR analysis
The infrared spectrum of the best synthesized product
is presented in Figure 4 (b). Each functional group
corresponds to a region of absorption wavelengths,
thus, it allows to identify the product. The stretching
vibrations of typical organic molecules tend to fall
within speciic regions of the infrared spectrum, as
shown in Table 1. Intermediate diesters have higher
relative intensity in OH region due to terminal
hydroxyl vibration at 3448 cm-1 as a result of higher
proportion of hydroxyl end groups compared to
unsaturated polyester.
In the synthesized polymer, this hydroxyl peak
diminished with the reaction time due to decreasing
relative amount of present end groups in the polymer.
The ester carbonyl bonds and C=C stretching appear
at 1726 cm-1 and 1646 cm-1, respectively. After transesteriication of intermediate, a noticeable decreasing
in OH band at 3448 cm-1 was observed due to the
obvious removal of propylene glycols.
The FTIR spectra should be emphasized on the
absence of the mentioned peaks that conirms the
improvement of esteriication reaction. According
to the literature, free carbonyl groups should appear
at 1690 cm-1. At lower wavenumbers, signiicant
peaks, which are presented around 1226 cm-1, may be
attributed to C-O linkages.
37
Two novel methods for synthesizing poly (propylene fumarate): Technical aspects and role of vacuum and N2 purging effects
Reaching low terminal OH bands means obtaining
the ine product. As shown in Figure 4 (b and c), the
FTIR spectra indicate that a signiicant diminishing of
the OH groups after 14h in MRS and 17 h in MRDS
are achieved.
Comparison of some effective parameters in
synthesizing PPF by primary studies
The FTIR analysis data based on increasing the
molecular weight with time can be used to characterize
the conversion of intermediates to the inal product.
The presence of terminal OH groups in FTIR spectra
plays an important role in distinguishing the different
steps of PPF synthesis. The reduction of peak intensity
of OH groups demonestrates that the polycondensation
reaction is occurred. The more progress is made in
the polycondensation reaction, the higher molecular
weight is achieved. Furthermore, decreasing the
intensity of OH region means that the synthesizing
process is going on correctly [23].
The FTIR spectra indicate a signiicant diminishing
of the OH groups after 13- 14 hours ( 2c, 3b and 4d
(MRS) in Table 2 and Figure 5). The PPF with Mn
of 1167 gr/mol and Mw of 2195 gr/mol which was
produced after 17 h in MRDS was identiied as the
best product (2d in Table 2 and Figure 5).
Generally, the reaction rate is fast and products
with higher molecular weight are obtained in higher
temperatures. In the lower temperatures of 90-105°C
(3a in Table 2 and Figure 5), the reaction is very
slow [23, 24]. But, the products decompose at the
temperatures higher than 160°C (3c and 3d in Table
2 and Figure 5).
In order to obtain higher degrees of polymerization,
IPPI
the removal of polypropylene glycol as a by-product
from the reactor is necessary for the second stage.
Removing the propylene glycol is dificult; thus,
the vacuum should be applied correctly to facilitate
this process [23, 25]. Obviously, decreasing PG by
applying vacuum continuously leads to changing the
stoichiometry of the reactants and premature end of
the reaction. However, it seems that applying vacuum
stepwise in some procedures such as MRS leads to a
low reproducibility (4c and 4d in Table 2 and Figure
5) and in some procedures such as MRDS (2d in
Table 2 and Figure 5) leads to a high reproducibility.
Moreover, applying vacuum continuously in the other
procedures are not suitable for synthesizing PPF ((4a
and 4b in Table 2 and Figure 5)
The reaction time is increased by increasing the
molar ratio of PG: DEF from 1.5 to 4 without applying
vacuum (1a-1d in Table 2 and Figure 5) and the
polymerization is also proceeded. So, more glycol (
in an acceptable range) leads to the increase of the
reaction time and makes it controllable (1c and 1d in
Table 2 and Figure 5) [23].
The data in the table indicates clearly that few
changes in each parameter result in large effects on
quality of the inal product. In fact, the PPF is very
inluenced by the parameters of polymer synthesis.
MRDS is a new clear designed method which is
a combination of several well-known methods in
polymer science that not only can facilitate PPF
synthesis as a biopolymer for biomedical application,
but also provide a certain method in PPF synthesis
with very high reproducibility and eficiency. Finally,
in MRDS, 1:3.5:0.01:0.002 molar ratio (DEF: PG:
ZnCl2: hydroquinone) of the reactants with stepwise
Table 3. Technical aspects and results of the synthesized PPF obtained by using MRS and MRDS.
Methods
(h) Time
MRS
2 phases-14
(phase 1:
6-7h /phase
2:6-7 h)
MRDS
2 phases-17
(phase 1:
6-7h /phase
2:10 h)
38
Final
temperature
(°C)
Applying vacuum
Stepwise over
phase 2
140
10 times for 5
min 30 min, every
over phase 2
Stepwise over
phase 2
140
10 times for 5
min 30 min, every
over phase 2
N2 purging
continuous-non
in the irst step
(Continuous during
2.5h and then
under N2 blanket)
Continuous
in the irst step
(5bubbles/second)
Properties of the
products
Collected PG and
ethanol
FTIR
22% V of initial PG
and DEF
Dark brown- high
viscosity / Lack
of reproducibility
Light brown- high
viscosity/ high
reproducibility
(accumulation of
ethanol in the irst
step)
Figure4
(c)
21% V of initial PG
and DEF
(no accumulation
of ethanol in the
irst step)
Figure 4
(b)
Polyoleins Journal, Vol. 4, No. 1 (2017)
Shahbazi S. et al.
applying vacuum, 17 h reaction time, and 140 °C
temperature has been obtained as the best formulation
in the PPF synthesis.
The advantages of MRDS compared with current
methods are listed in the following:
1. Due to the lack of ability to fully remove of
byproducts from the reactor in the relux current
systems and in order to develop the reaction, the other
parameters must be changed to compensate changing
parameters including:
• Increasing reaction time that can damage double
bonds in PPF structure and also has not suitable
industrial scale perspective.
• Applying higher temperature can damage the
double bonds in the PPF structure and may result
in decomposition of polymer structure. In addition,
increasing the temperature above the desired
temperature, not only is not economical, but also
creates some undesirable byproducts that affect the
eficiency of the reaction.
• The use of some strong catalysts such as p-toluene
sulfonic acid can inluence the progress of polymer
reaction and may create the different structures of
PPF with various molecular weights [26]. Thus, by
applying MRDS for synthesizing PPF, producing
undesirable byproducts out of the reaction kinetics
may be reduced.
2. The MRDS strongly increases the eficiency of the
polymerization reaction. This methodology allows to
prepare polymers by polycondensation reaction in a
high quality, eficient and reproducible manner.
3. The MRDS can be very effective in the
polycondensation reactions, because in addition of
the main products, byproducts can be used, too. Thus,
purity of by-product is important and can be provided
with MRDS.
IPPI
Furthermore, Table 3 shows technical aspects and
results of synthesized PPF by MRS and MRDS.
H-NMR spectroscopy
H-NMR spectrum of synthesized PPF by MRDS is
presented in Figure 6. The chemical shifts appeared
at 6.8 ppm (vinyl protons), 5.3 ppm (-CH), 4.3 ppm
(-CH2) and 1.2 ppm (-CH3) conirm the chemical
structure of PPF.
GPC analysis
The results obtained from the synthesis and
characterization of some samples by FTIR show that
the best product has a number average molecular
weight (Mn) of 1167 g/mol, the weight average
molecular weight (Mw) of 2195 g/mol and PDI of 2.8.
The GPC analysis of the PPF obtained by MRDS has
been shown in Figure 7.
CONCLUSION
A new mixed relux-distillation system (MRDS)
was used for synthesizing PPF via esteriication
reaction. Usefulness of new reaction method results
from that all common techniques are ineficient from
energy, time, and cost point of views. The reactions
could be carried out without employing any special
equipment. Vigreux condenser facilitated to retain the
monomers in the reactor and to obtain optimum PPF
molecular weight. Modiied relux system (MRS) was
less eficient than the MRDS. However, in MRDS,
reluxing and distillation processes were performed
continuously. Pure propylene glycol as a by-product
also indicated that the reaction had a higher yield.
Thus, this novel system could be considered as a
very suitable, eficient and reproducible technique
in synthesizing PPF. Nitrogen gas, vacuum applying
position,
continuously/stepwise-continuously
applying vacuum and other parameters showed an
important role in the polymerization of PPF in both
the systems.
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