Continuous reactor technology for ketal formation: An improved synthesis of solketal

Article abstract of DOI:10.1021/op000135p

The development of a fully continuous process for the synthesis of solketal (4-hydroxymethyl-2,2-dimethyl-1,3-dioxolane) is described. The use of a heterogeneous catalyst, recycle of unreacted starting material, elimination of the need for an entraining solvent, and purification of the product in situ all afford improvements over existing processes. Data generated in model reactions is used to prove the applicability of the process to a counter-current distillation reactor design, and to compute the operating parameters of the reactor.

Full text of DOI:10.1021/op000135p

Organic Process Research & Development 2001, 5, 630−635
Continuous Reactor Technology for Ketal Formation: An Improved Synthesis of
Solketal
Jay S. Clarkson, Andrew J. Walker,* and Michael A. Wood
KVaerner Process Technology Ltd, The Technology Centre, Princeton DriVe,
Thornaby, Stockton-on-Tees TS17 6PY, United Kingdom
Abstract:
point; chloroform and petroleum ether4a,b,5 have been em-
ployed. The use of an entrainer is undesirable from the aspect
of product purity and (particularly in the case of chloroform)
for environmental reasons; thus, the use of excess acetone
as a stripping agent for water removal has been previously
The development of a fully continuous process for the synthesis
of solketal (4-hydroxymethyl-2,2-dimethyl-1,3-dioxolane) is de-
scribed. The use of a heterogeneous catalyst, recycle of unre-
acted starting material, elimination of the need for an entraining
solvent, and purification of the product in situ all afford
improvements over existing processes. Data generated in model
reactions is used to prove the applicability of the process to a
counter-current distillation reactor design, and to compute the
operating parameters of the reactor.
6
proposed.
The use of a heterogeneous acidic catalyst would facilitate
separation from the final reaction mixture. Such catalysts
4
a,b
have been used in batch processes,
and in continuous
4d
fixed-bed processes. Although offering improvements over
the historical batch process, none of the continuous processes
to be found in the literature offers an ideal process for the
synthesis of solketal. It was proposed that the counter-current
reaction column developed and patented by Kvaerner Process
Technology for esterification processes could be utilised
in an extremely efficient synthesis of acetals; the parameters
for this process have been established.
Introduction
Solketal (3, Scheme 1) is a versatile solvent and plasti-
ciser, also used as a solubilising and suspending agent in
pharmaceutical preparations. Solketal is formed from glyc-
7
,8
1
erol (2) and acetone (1) in an equilibrium reaction (Scheme
1
), which typifies the formation of acetals and ketals from
2
Reactor Design
alcohols and carbonyl compounds. In a traditional batch
process, the reaction is catalysed by a homogeneous acid
catalyst (sulfuric or p-toluenesulfonic acid). The equilibrium
The reaction column was originally developed for the
commercial-scale production of methyl esters of fatty acids
and has subsequently been applied to a range of other
esterification reactions, including the esterification of mono-
methyl maleate to dimethyl maleate as part of the process
3
constant for ketalization is unfavourable, and the equilibrium
has to be driven to the right by the use of a large excess of
one of the reagents (acetone) or by the removal of water of
reaction. This process suffers from the inefficiencies inherent
in all batch processing (poor mass transfer, high down-time,
significant by-product formation, intensive labour require-
ments); plus the cost of separating the product from the
homogeneous catalyst and excess reagent. These problems
have been addressed in the development of an improved,
continuous process for the production of solketal.
8
for the synthesis of 1,4-butanediol. The reactor is essentially
a multitray reactive distillation column with deep reaction
stages containing catalyst in suspension (Figure 1). The key
factors of any esterification reaction that influenced the
design of the reaction column are:
1. An equilibrium reaction, which can be driven to
completion by the removal of one of the products.
2. A solid catalyst (ion-exchange resin) system facilitates
separation and minimises waste.
Continuous process flowsheets have been previously
proposed for the formation of solketal. Typically in these,
the equilibrium reaction is driven by the continuous removal
of water from the reaction mixture, usually by the use of an
3. A nonvolatile reagent, which flows down the column.
4. A volatile reagent, which passes up the column in the
vapour phase, agitating the resin.
4
entrainer. The low boiling point of the acetone reagent
demands the use of an entrainer having a still lower boiling
5. A nonvolatile product, which flows down the column.
6
. A volatile by-product, which is stripped out of the
*
To whom correspondence should be addressed. E-mail: andrew.walker2@
reaction mixture by the upwards passage of the volatile
reagent.
Each reaction stage in the reaction column holds a given
amount of resin catalyst and provides residence time for the
reaction to occur; thus, the liquid depth is greater than on a
kvaerner.com.
(
1) (a) Merck Index, 11th ed.; Budavari, S., Ed.; Merck & Co. Inc.: Rahway,
NJ, 1989. (b) Ger. Offen 3447783, 1986. (c) PCT Int. Appl. 88 05071,
1
988.
(
(
(
2) Schmitz, E.; Eichhorn, I. In The Chemistry of the Ether Linkage; Patai, S.,
Ed.; Interscience: New York, 1967; pp 309-351.
3) Organic Syntheses; Wiley & Sons: New York, 1955; Collect. Vol. III, p
5
04.
4) (a) Barili, P. L.; Biagi, G.; Giorgi, I.; Livi, O.; Scartoni, V. J. Heterocycl.
Chem. 1991, 28, 1351. (b) Mi sˇ i c´ -Vukovi c´ , M.; Radojkovi c´ -Veli cˇ kovi c´ , M.;
Jovanovi c´ , S. J. Serb. Chem. Soc. 1993, 58(12), 1111. (c) U.S. Patent
(5) Japanese Patent JP10195067A2, 1998.
(6) U.S. Patent 5,917,059, 1999.
(7) Walker, A. J. Spec. Chem. 1999, 19(8), 364.
(8) (a) U.S. Patent 5,536,856, 1996. (b) U.S. Patent 5,157,168, 1992.
5
,917,059, 1999. (d) Kempe, J.; Kiessling, G. Z. Chem. 1986, 97.
6
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10.1021/op000135p CCC: $20.00 © 2001 American Chemical Society and The Royal Society of Chemistry
Published on Web 07/21/2001

Scheme 1
Figure 1. Cross-section of a CCR tray.
conventional distillation tray. Consequently, a proprietary tray
8
design was developed to accommodate the required liquid
hold-up while retaining the fluidised catalyst within the stage.
For a given reaction, reactor performance (kinetics, selectiv-
ity) and design (number of stages, internal dimensions) can
be calculated from the results of small-scale tests carried out
in sealed tubes and standard stirred-tank reactors.
Figure 2. Effect of reaction temperature on the conversion of
glycerol over time. *Experiment 6: batch experiment, acetone:
glycerol molar ratio 2:1.
catalyst (a sulfonic acid-functionalised ion-exchange resin,
Amberlyst DPT-1) was found to be the most efficient catalyst
for the ketalisation of glycerol.
Results and Discussion
The flowsheet concept proposed that acetone should serve
three functions in the process; reactant, agent for three-phase
mixing to enhance mass transfer, and stripping agent to
remove water of reaction and to drive the reaction forward.
In the reaction column, liquid glycerol would be fed into
the top of the reactor. The simple test reactor comprised a
stirred flask containing catalyst plus glycerol into which
liquid acetone was fed via a dip tube. The reaction mixture
was maintained at a temperature above the boiling point of
acetone, and excess acetone and water of reaction were
continuously distilled out. This is effectively a semi-
continuous reactor (batch with respect to glycerol and
solketal, continuous for acetone and water by-product).
Reaction Kinetics
Initial experiments were carried out at over a range of
temperatures to determine the kinetics of the reaction (Figure
2
). To facilitate throughput of acetone vapour through the
reaction system while avoiding the expense of constructing
a reactor to handle reduced pressures, the baseline experiment
(experiment 1, Figure 2) was performed at 72 °C, 15 °C
above the boiling point of acetone. Quantitative conversion
was achieved after 300 min. Surprisingly, increasing the
reaction temperature resulted in considerably reduced con-
version at 300 min (experiments 2-4). It was postulated that
this was due to the decrease in the concentration of acetone
present in the liquid reaction mixture (Figure 3). Consider-
ation of the vapour pressure curve for acetone (Figure 4)9
suggested that even a slight reduction in the reaction
temperature would give a significant increase in acetone
concentration of the reaction mixture, and this proved to be
the case. Experiment 5, carried out at 70 °C, gave quantitative
Choice of Catalyst
Potential by-products of the process include the self-
condensation products from both reagents. Ether formation
by condensation of 2 mol of glycerol and aldol condensation
between 2 mol of acetone both had to be minimised. A
proprietary catalyst has been developed for esterification
processes (fatty acid esters and dimethyl maleate) which
specifically minimises ether-forming reactions, and this
(9) CRC Handbook of Chemistry and Physics, 76th ed.; Lide, D. R., Ed.; CRC
Press: Boca Raton, 1995; pp 6-82.
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631

Table 1. Equilibrium composition of the reaction mixture
at 70 °C
composition (wt %)
acetone:glycerol
expt initial molar ratio acetone glycerol solketal water
Fresh Ion-Exchange Resin
1
1
1
1
2
3
1:1
2:1
3:1
23.8
45.5
53.2
22.2
0.4
0.2
46.5
46.1
38.8
5.4
6.4
6.5
Recycled Ion-Exchange Resin
1
1
1
4
5
6
1:1
2:1
3:1
29.1
52.5
61.7
18.4
1.5
<0.1
43.7
39.1
32.4
5.4
5.4
4.5
molar concentration of acetone was having a disproportionate
effect on the rate of reaction towards equilibrium. A series
of sealed-tube experiments were carried out to determine the
equilibrium position of the reaction at 70 °C and at various
acetone concentrations. The results are shown in Table 1.
Using a 1:1 molar ratio of acetone to glycerol, the reaction
mixture at equilibrium was found to contain 47% solketal
(
experiment 11), confirming results published in the literature.4d
The resin from each of these tests was reused (without
treatment) in a similar experiment (Table 1, experiments 14-
Figure 3. Effect of reaction temperature on the acetone
concentration in the reaction mixture over time.
1
6; resin from experiment 11 was used in experiment 14,
etc); only a slight loss of catalytic activity was observed. A
stirred-flask experiment was carried out at ambient temper-
ature, in which a 100% mole excess of acetone was added
to glycerol in the presence of Amberlyst DPT-1 resin (5 wt
%), and the mixture was stirred as normal. The equilibrium
concentration of solketal in the reaction mixture was
confirmed to be in excess of 97% (experiment 6, Figure 2).
It was difficult to determine the time taken to come to
equilibrium at room temperature; glycerol and acetone are
immiscible, and in the early stages of the reaction the mixture
forms two phases.
From these experiments at ambient pressure, an optimum
acetone:glycerol molar ratio of 2:1 was determined, this being
the ratio above which minimal improvement in glycerol
conversion was obtained. The optimum reaction temperature
corresponding to the optimum acetone:glycerol ratio at
ambient pressure was thus determined to be 70 °C (repre-
senting a liquid acetone concentration of 43-45 wt %).
A series of experiments were carried out to determine
the optimum catalyst loading; the results are depicted in
Figure 5. The optimum level of 5 wt % with respect to
glycerol was used as the standard when establishing the other
parameters.
Use of Wet Starting Material
Figure 4. Vapour pressure curve of acetone.9
A considerable saving in the cost of the raw materials
for this process can be made if wet glycerol is used (glycerol
conversion in only 240 min. The net result is an increase in
throughput, as the reduction in reaction time more than
compensates for the increased dilution of the reaction
mixture. Operating at a lower reaction temperature also
minimises the formation of ethers (by-products from alcohol
dehydration); final concentration is typically <0.1 wt %.
The high conversion in the early stages of the reaction
carried out at 70 °C led us to speculate that the increased
5
is hygroscopic). To this effect, work was carried out to
determine the most effective reaction parameters if solketal
were to be synthesised in a reaction column from glycerol
containing 20 wt % water (Figure 6). Carrying out the
reaction at 70 °C (experiment 9) resulted in considerably
decreased conversion at 300 min (72%, cf. 100% when using
dry glycerol). However, utilising a ramped reaction temper-
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then decreasing the temperature to 70 °C for the remainder
of the reaction to build up the liquid acetone concentration
and drive the equilibrium. In a fully continuous reactor, the
same effect would be achieved by varying the temperature
profile through the reactor, rather than by varying it with
time.
In all experiments, the reaction was found to be particu-
larly clean. The formation of the aldol condensation product
of acetone (2-hydroxy-2-methylpentan-4-one) was the only
side reaction, and this by-product was present only in low
concentration (<1.0 wt %).
Flowsheet Design and Reactor Profile
The results of the semi-continuous and sealed tube
experiments were used to compute a reactor profile for the
formation of solketal from a glycerol feedstock having a
water concentration of 20 wt %. The reactor design (Figure
7
) incorporated two high-temperature feed stages at the top
of the reactor; these would operate empty of catalyst to
remove water from the glycerol. The glycerol feed would
be preheated and fed into feed stage 1, and a reboiler would
be used to maintain feed stages 1 and 2 at 90 °C. A residence
time of 30 min per stage should see water concentration
reduced to 6 wt % in the first reaction stage.
Figure 5. Effect of catalyst loading on the conversion of
The data from the laboratory experiments were used to
calculate, that in a reaction column, a residence time of 30
min per stage would afford a minimum glycerol conversion
of 70% per stage at 70 °C. The initial (higher) reaction stages
would be constrained to operate at temperatures higher than
the optimum (being directly below the feed trays) and would
thus afford proportionately lower conversions. The temper-
ature profile is set by the latent heat differences between
the reactant (acetone) vapour and the product (water) vapour;
heat-exchange coils on the reaction trays should not be
required. It was calculated that, to give a final product purity
glycerol over time.
>
99.0 wt %, 10 reaction stages would be required, each
affording a residence time of 30 min (at the specified 5 wt
catalyst concentration) and operating according to the
temperature profile and rates of conversion depicted (Figure
). The predicted composition of the reaction mixture on
%
7
each stage is also shown in Figure 7 (formation of organic
by-products has been ignored in these calculations, but by-
product concentration in the final reaction tray would be
expected to be <0.5 wt %). As there is a considerable
difference in volatility between solketal and acetone, final
product purification can be accomplished by having three
distillation stages below the final reaction stage, each
operating at a successively higher temperature. Residence
time for the reactor as a whole is 7.5 h.
It should be emphasised that this section describes a model
for a continuous commercial-scale reactor, the dimensions
of which will be dependent on the product demand. For
example, a reactor with an internal diameter of 6 in would
afford approximately 15 kg solketal per h (120 tonnes per
year).
Figure 6. Comparison of glycerol conversion rates starting
with wet and dry feedstocks, using different temperature
profiles.
ature profile (experiment 10), which can be readily provided
in a commercial reaction column, enabled the conversion at
3
00 min from wet glycerol to be increased to a level (>98%)
approaching that achieved using dry glycerol (experiment
). The ramped temperature profile involved carrying out
5
Conclusions
the reaction at a higher temperature (90 °C) for the first 90
min to facilitate removal of water from the reaction mixture,
The formation of solketal from glycerol and acetone is
ideally suited to the reaction column reactor design, par-
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633

Figure 7. Reactor design, operating parameters and calculated reaction mixture composition for continuous solketal production.
ticularly when there is an extra need to drive the equilibrium
i.e., if water is present in the glycerol starting material).
Features of the reaction column offering improvement over
existing processes include:
temperature to drive water out of the reaction mixture.
Middle and lower stages can be run at a lower temperature,
driving the equilibrium further by building up the acetone
concentration. Alternatively, the reactor can operate under
a positive pressure, allowing acetone concentration to be
increased without increasing the reaction temperature, or
allowing reaction temperature and hence reaction kinetics
to be increased.
(
1. Heterogeneous catalyst facilitates separation from
product.
2. Stripping of water from the reaction mixture by
entrainment drives the equilibrium.
3
. Use of acetone as both reagent and entrainer simplifies
5. Feeding acetone part-way up the column allows the
bottom stages of the reaction column to act solely in a
distillation capacity, eliminating the need for further product
purification (solvent stripping).
product purification and improves throughput. The by-
product wet acetone can be easily dried by distillation and
recycled without the need for an expensive azeotrope splitter.
4
. Different stages in the reaction column can be run at
Work is continuing on applying the reaction column
reactor concept to other ketal-forming reactions (particularly
acyclic ketals where the entropy of the reaction disfavours
different temperatures. For example, if wet glycerol is used,
the upper stages of the reaction column can be run at a higher
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the equilibrium conversion) and to other types of reactions
which meet the criteria for this type of reactor.
ously into the reactor via a metering pump (300 g/h) and
dip-tube while the temperature of the mixture was maintained
at a constant value. Any vapour was distilled off and
collected by condensation. The reactor contents and distillate
were sampled (0.1 mL) at 10 min intervals for 30 min, then
30 min intervals for 90 min, and 60 min intervals for a further
360 min, giving a total reaction time of 480 min.
Sealed-Tube Experiments. Glycerol (10.2 g, 110.7
mmol), acetone (6.4-19.3 g, 110.7-332.1 mmol), and ion-
exchange resin Amberlyst DPT-1 (0.51 g, 5 wt %) were
charged to a pressure-resistant tube. The tube was sealed
and heated at 70 °C with shaking for 16 h. At the end of the
reaction the mixture was decanted from the resin and
analysed. The resin was recharged to the tube, and fresh
glycerol and acetone were added in the same amount as
previously. The experiment was repeated as before.
Experimental Section
Conversions and selectivities were determined by GC
methods. GC were measured with a Perkin-Elmer Autosys-
tem XL equipped with FID detection on a CP wax (30 m)
column; data collection and evaluation were performed using
Perkin-Elmer/Nelson Turbochrome 4. Products were identi-
fied by comparison with authentic standards.
Water concentrations were determined by a conventional
Karl Fischer titrametric method.
All chemicals were purchased from standard sources.
Semi-continuous Reactor Experiments. Glycerol (204
g, 2.21 mol) and ion-exchange resin Amberlyst DPT-1 (10.2
g, 5 wt %) were charged to a 500 mL, four-necked flask
equipped with a mechanical impeller stirrer, digital ther-
mometer, dip-tube inlet, and total offtake distillation head.
The reaction mixture was stirred (400 rpm) and warmed to
the required reaction temperature. Acetone was fed continu-
Received for review December 27, 2000.
OP000135P
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