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Continuous flow synthesis of polyIJacrylic acid) via

Cite this: React. Chem. Eng., 2017, 2,
free radical polymerisation
662
Laurens Brocken,a Paul D. Price,b Jane Whittakerb and Ian R. Baxendale *a

Received 12th May 2017, The free radical polymerisation of aqueous solutions of acrylic acid (1) has been studied using a continuous
Accepted 14th July 2017
flow reactor to quickly screen reaction parameters such as temperature, residence time, monomer- and
Published on 14 July 2017. Downloaded on 7/5/2018 8:19:33 AM.

initiator concentration. The experimental data sets produced established a theoretical basis for conducting
DOI: 10.1039/c7re00063d
scale up processes to efficiently produce larger quantities of polyIJacrylic acid) delivered with good control
rsc.li/reaction-engineering over the molecular weight and dispersity.

1 Introduction cause processing difficulties increasingly they are being

shown to be less restrictive if planned for in advance as part
Since the early 1990s there has been a steady growth within of the flow process.17–22
both academia and industry with regards to the use of flow Although flow chemistry has been predominantly the do-
reactors for the synthesis of chemical compounds due to the main of chemists and engineers working on the preparation
increase in reaction control afforded.1–7 In general, flow of small molecular weight compounds it has recently started
chemical synthesis offers several advantages over batch chem- to gain more traction in the synthesis of macromolecular
istry. For example, the reactors provide excellent heat transfer systems.23–28 Indeed, several types of polymerisation have al-
meaning reaction temperatures can be rapidly changed in- ready been shown to benefit from the application of various
cluding accessing different sequentially linked temperature flow processing techniques which have been comprehensively
zones or facilitating super heating of solvents within an easily summarised in a few recommended review articles.29–33 Con-
pressurised reactor. Mixing within flow channels can also be sidering all the potential polymerisation methods, free radi-
additionally enhanced generating more consistent reaction cal polymerisation is of particular interest from an industrial
domains leading to better control and improvements in yield stand-point. A major virtue of free radical polymerisation is
and purity. Automation of flow reactions enables better pro- that it can be typically carried out under relatively
cess control expedited via direct in-line analysis which can undemanding conditions, allows for a wide range of mono-
also be used in reaction feedback loops (RFL) and design of mers to be used and exhibits a high tolerance to stabilisers
experiment (DoE) routines.8–16 Additional aspects of en- which are often present in the monomers.34 However, control
hanced safety and the flexibility to conduct multi-step synthe- over the molar mass distributions (MMD) in this type of poly-
ses through integrated processing sequences leading to more merisation is harder to achieve requiring much more precise
complex chemical architectures are also advantageous.17,18 It regulation of the reaction parameters. Therefore generating a
should however be acknowledged that flow chemistry also new free radical derived polymer necessitates time intensive
has some drawbacks. The key issues are often associated with screening of the various reaction parameters, ensuring con-
high investment costs in both equipment and training; diffi- sistency of the polymerisation process and enabling the
culties in compensating for varying kinetics, dilution effects targeting of specific molecular weights. A solution to this
and the compatibility of the potentially different solvents in problem may be found in the use of flow chemistry as this
continuous multi-step sequences. Problems can also be en- technique has repeatedly proven its strength in efficiently
countered relating to precipitation of intermediates/product evaluating reaction parameters in a fast serial screening
or increases in viscosity during reactions. In addition having mode. Consequently the aim of this research was to screen
to process sufficient material to achieve steady-state operation and then define flow processing conditions to access various
can use up valuable resources. Although these aspects can target molecular weight polymers which could then be repro-
ducibly processed in a continuous mode to prepare larger
a
quantities of material.
Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE,
UK. E-mail: i.r.baxendale@durham.ac.uk; Fax: +44 (0)191 334 2051;
PolyIJacrylic acid) was selected for study as it has been ex-
Tel: +44 (0)191 334 2185 tensively researched and its behaviour is well known yet it
b
Unilever R&D Port Sunlight, Quarry Road East, Bebington, Wirral, CH63 3JW, UK presents several challenges in its synthesis.35–38 The acrylic

662 | React. Chem. Eng., 2017, 2, 662–668 This journal is © The Royal Society of Chemistry 2017
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acid monomer (1) is highly reactive,39 which raises two prob- channel A and B respectively. The flow rates on each channel
lems. First, due to the high polymerisation rate and exother- were always maintained at a 1 : 1 ratio and were adjusted to
mic nature of the process, heat evolution is an issue requir- produce different residence times for the reactions. A PEEK
ing careful regulation to control the reaction progress. This is cross assembly (1.30 mm thru hole and 22.8 μL swept volume
necessary for a safe synthesis and to avoid gel formation. Sec- fitted with a pressure transducer – obtained from Uniqsis
ondly the final product inherently has a very high molar Ltd., Shepreth, United Kingdom) was placed in-line to com-
mass. Indeed, to obtain polyIJacrylic acid) with a low molar bine the two flows into a single homogeneous stream. The
mass, a low concentration of acrylic acid (1) is prepared flow path was configured so that the channel A and B entered
which results in large batch volumes upon scale-up.40 Addi- laterally and the mixed flow exited at right angles, which then
tionally, diffusion is an important phenomenon in free radi- passed into a 52 mL FEP coil which could be heated at differ-
cal polymerisation.41 This aspect has different names in each ent temperatures. A back pressure regulator (BPR, 100 psi)
mechanistic step, such as the cage effect for the initiation, was placed at the exit to the coil reactor. The exiting solution
glass effect for propagation and Tromsdorff or gel effect for of polyIJacrylic acid) was collected in a stirred flask containing
termination, however at each stage good control over diffu- sodium selenite (0.005 mM) as a radical quencher to terminate
sion is necessary to achieve well defined polymers. It was any radical species and prevent further polymerisation (Fig. 1).
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anticipated that here again the advantages associated with

flow processing relating to heat transfer, mixing and continu- 2.3 Characterisation
ous operation would provide advantages creating an im- For each transformation the monomer conversion was deter-
proved synthesis. mined by 1H NMR, spectra were recorded using water sup-
pression on either a Bruker-Avance 400 or Varian VNMRS-600
2 Experimental instrument. A 10% by volume aliquot of D2O was added in
2.1 Materials order to create a signal lock. Conversion was calculated based
Acrylic acid (1) (Alfa Aesar, 99%), 2,2′-azobisIJ2- upon the determination of residual acrylic acid monomer in
methylpropionamidine) dihydrochloride (2) (Sigma Aldrich, the sample at a known concentration. The technique used
97%), sodium selenite (Alfa Aesar, 98%), 1,2-dimethoxyethane was based on the Watergate43 suppression technique as
(DME, Alfa Aesar, 99% stabilized with BHT) and deionised described by Morris et al.44,45 Although this technique is a
D2O were used without further purification. The flow polymer- powerful method to measure water rich samples it also has
isation was carried out on a FlowSyn (Uniqsis, Shepreth, drawbacks. Bleaching of signals near water, saturation of
United Kingdom), a reactor system available from Uniqsis Ltd. exchangeable NH protons (for presaturation) and a tilted
base line created by a large dispersive tail of the water signal
2.2 Polymerisation need be taken into consideration when analysing the results.
For these reasons an internal standard (DME) which was not
Stock solutions of acrylic acid (1) and initiator (2) were pre- affected by the water suppression was chosen to calibrate the
pared in deionised water at known concentrations (Table 1). conversion of acrylic acid (1). Gel permeation chromatogra-
It is well known that, under free radical reaction conditions phy (GPC) analysis of the polyIJacrylic acid) samples was
in concentrated homogeneous mixtures, gel formation can performed using a Viscotek GPC max 2001 triple-detection
occur as soon as the conversion becomes high enough. It is system in aqueous solution (0.05 mol L−1 NaNO3, 2.81
also generally understood that the viscosity of reaction me- mmol−1 NaOH and MeOH [ratio 4 : 1] using 2 × A6000M +
dium will constantly increase with increasing conversion.42 guard column set (all purchased from Malvern)). The column
This can potentially become an issue using flow processing and detector temperature was 50.00 °C, flow rate was 1.0000
techniques where significant increases in viscosity followed mL min−1, injection volume was 50 μL and volume increment
by gel formation must be avoided to prevent clogging of the was 0.00333 mL.
reactor. To limit the potential risks from clogging the maxi-
mum molecular weight and limiting monomer concentration 2.4 Analysis
were not researched. The maximum concentration of used
monomer in this set-up was restricted to 1.0 mM. The conversion of monomer into polymer was determined by
The two stock solutions were pumped through a FlowSyn adding DME as an internal standard (either 5 mM or 10 mM)
reactor using the two independently controlled HPLC pumps,

Table 1 Screening parameters for acrylic acid (1) polymerisation

Temperature Acrylic acid Initiator Residence time

(°C) (mM) (1) (mol%) (2) (min)
70 0.4, 0.7, 1.0 1.25, 2.50, 3.75 5, 10, 20, 30
80 0.4, 0.7, 1.0 1.25, 2.50, 3.75 5, 10, 20, 30
90 0.4, 0.7, 1.0 1.25, 2.50, 3.75 5, 10, 20, 30 Fig. 1 Flow scheme for the polymerisation of acrylic acid (1).

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Paper Reaction Chemistry & Engineering

to the monomer stock solution. The standard used to assess of elevated temperatures is however that extensive backbiting
the GPC system prior to each run was PEO (22 kDa, dn/dc within the polymer will occur.46 As can be seen from the plots
(ml g−1) 0.1320, dispersity 1.045). For the GPC data outlying (Fig. 2) a secondary contributing effect on conversion was the
values were eliminated based upon the processed data
(OmniSEC 4.7 software was used to build method and pro-
cess data). To determine the average molecular weight and
dispersity a minimum, of two measurements were used. Ex-
treme outlaying data points relating to molecular weight and
dispersity were removed from the data-set if these values de-
viated more than 10% from the mean value.

3 Results and discussion

Using the specified flow setup described above (Fig. 1) rapid
screening of up to ten different test conditions could be
conducted in a single working day (8 h), generating values
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for monomer conversion with associated dispersity and mo-

lecular weight range. The full data set represented by Table 1
was performed to generate a comprehensive profile of the
polymerisation reaction in flow.

3.1 Initiator
At the conclusion of a conventional batch polymerisation of
acrylic acid (1) it is common to add an extra dose of initiator
to the reaction mixture to ensure any residual monomer is
fully consumed. This avoids the post reaction requirement
for expensive and time consuming sequestration of the
monomer from the polymer solution but inevitably leads to a
broadening of the dispersity. For this reason achieving full
conversion is an important aim with it being most desirable
to obtain full conversion of the monomer by exacting control
over the individual reaction parameters. In free radical poly-
merisation it is assumed that the initiator activation follows
first order kinetics. Therefore its half-life time is dependent
on the reaction temperature. High temperature will initialise
higher average radical concentrations. The higher the initia-
tor content, the shorter the polymers that will be formed as
the monomer concentration will not be sufficient to form
long chains. In our study three initiator concentrations were
selected; 1.25, 2.50 and 3.75 mol% of the monomer concen-
tration. The upper limit was fixed at 3.75 mol% to avoid any
potential problems resulting from clogging of the flow system
through gel formation. Conversely the lower limit was also
set as too low a value of initiator results in poor propagation
due to the cage effect. This would negatively affect the poly-
merisation as the initiator would not be consumed optimally.
This was considered particularly important for the short resi-
dence times we were targeting in this flow system.

3.2 Conversion
Both temperature and residence time contribute significantly
to the overall conversion of acrylic acid (1). In general a high
conversion could be reached at longer residence times Fig. 2 A plot of conversion (%) against temperature (°C) and residence
(Fig. 2). To obtain good conversion at shorter residence times time (min) at various initiator (2) concentrations, A: 1.25 mol% of
(i.e. 5 min) elevated temperatures were required. A drawback initiator (2), B: 2.50 mol% of initiator (2), C: 3.75 mol% of initiator (2).

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in molecular weight was observed as the reaction temperature

increased which can be ascribed to a corresponding increase
in the concentration of radical species (Fig. 4). Consequently
the amount of initiator added also greatly affects the molecu-
lar weight with a higher initial initiator concentration result-
ing in a higher concentration of initiator radicals and there-
fore multiple competing polymerisation events and a lower
final molecular weight (Fig. 5).48 This effect is more pro-
nounce at the higher temperatures evaluated as the initiator
half-life time is shorter and so the systematic changes in
starting initiator concentration are seen more significantly.
The final parameter that impacts the molecular weight is
the monomer feed concentration. High concentrations re-
sults in longer chains, as there is sufficient monomer for ex-
tended propagation. The temperature has a similar effect on
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the molecular weight in relation to monomer concentration.

Fig. 3 Conversion (%) versus temperature (C) using high acrylic acid
The molecular weight will increase for low temperatures
(1) concentration (1 mM) and low initiator (2) (1.25 mol%) input.
and high monomer concentration (Fig. 6A) but the relative

amount of initiator (2) used. For low monomer concentration

and high initiator ratio nearly full conversion was reached
(Fig. 3). It was also shown that polymerisations at lower tem-
peratures could also reach full conversion using high initia-
tor input and low monomer concentrations. A direct correla-
tion between the amount of initiator (2) and temperature
could be rationalised via the half-life of the initiator. The
half-life of initiator (2) is ten hours at 56 °C.47 The initiators
fragmentation is expected to follow the Arrhenius equation
and therefore the half-life at 80 °C would be in the order of
28 min. If the reaction residence time is below twice the half-
life time of initiator (2) full conversion is hard to achieve.

3.3 Molecular weight

As expected multiple parameters influence the resulting mo-
lecular weight of the polymers synthesised. A general decrease

Fig. 5 GPC date: decrease of molecular weight for increase of

initiator, the acrylic acid (1) concentration is kept constant at 1.0 mM
Fig. 4 Experimentally observed decrease of molecular weight over with A: 5 min residence time and B: 30 min residence time. Other
increase of temperature. residence times and acrylic acid (1) concentrations show similar trends.

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3.4 Dispersity
A narrow dispersity is generally desirable as it indicates a
more homogeneous polymeric sample. The major factors
influencing dispersity in our study were demonstrated to be
residence time and processing temperature. These two vari-
ables also strongly influence the overall conversion; a plot of
sample dispersity against conversion (%) is shown in Fig. 7.
As can be seen obtaining a high monomer conversion whilst
also maintaining a low dispersity is not readily achievable.
This is understandable when acknowledging that steady state
conditions for free radical polymerisation are arrived at very
rapidly, orders of magnitude below the residence times used
in this study. Therefore the rate of initiation will be equitable
to that of termination during the entire reaction; assuming
no limitation imposed by the initiator concentration or initia-
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tor half-life at the concentrations, residence times or temper-

atures investigated which was not the case. Consequently the
dispersity of the polymer sample will steadily increase during
the polymerisation process leading to a general broadening
of dispersity following a classical Schulz–Flory distribution.
In this respect a more progressed reaction – higher conver-
sion of monomer – will generally give a larger dispersity.

3.5 Target molecular weight

Having performed a systematic evaluation of the parameters
in flow we endeavoured to bring this knowledge together in
a predictive fashion in order to target under optimal con-
ditions a set of defined Mw polymers possessing narrow
dispersity. Consequently, randomly selected target molecular
weights from within three arbitrary groupings representing
low (80 000–200 000 g mol−1), medium (210 000–350 000 g
mol−1) and large (360 000–500 000 g mol−1) polymers were de-
fined. The predicted conditions were derived from a 3 × 3 × 4
Full Factorial Design and Least Square Fit model using JMP
Pro 12.1.0 software optimised for molecular weight. The ran-
domly generated values of 120 172, 311 133 and 448 542 g

Fig. 6 Molecular weight increases for higher monomer feed. Lower

temperature will increase the molecular weight. Residence time is 30
minutes, A: polymerisation at 70 °C, B: polymerisation at 80 °C and C:
polymerisation at 90 °C.

difference is the same for the different monomer concentra-

tions (Fig. 6). Fig. 7 Influence of conversion on dispersity.

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Table 2 Parameters targeted molecular weights and obtained results

Predicted conditions Obtained results

Target Mw Temperature Residence time Acrylic acid (1) Initiator (2) Mw Mw
(g mol−1) (°C) (min) (mM) (mol%) (g mol−1) Dispersity (g mol−1) Dispersity
120 000 87 19.5 0.764 2.60 120 000 3.22 118 000 6.69
310 000 73 10.0 0.785 1.26 311 000 1.48 333 000 2.43
450 000 76 29.0 1.100 1.27 449 000 2.10 477 000 7.53

mol−1 along with the predicted parameters to synthesise the Acknowledgements

target polymers are given in Table 2. Upon performing the re-
actions under the defined reaction conditions analysis via We are greatful for financial support by Unilever and EPSRC
GPC indicated a reasonable and reproducible correlation with (RG64908 to LB) and the Royal Society (UF130576 to IRB).
a difference from predicted of 1.5% for low, 6.7% for me-
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