Computers and Chemical Engineering 35 (2011) 177–189

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Computers and Chemical Engineering

journal homepage: www.elsevier.com/locate/compchemeng

Derivation of optimal operating policies under safety and technological

constraints for the acetoacetylation of pyrrole in a semi-batch catalytic reactor
Gheorghe Maria ∗ , Anca Dan
Department of Chemical Engineering, University Politehnica of Bucharest, P.O. 35-107, Bucharest, Romania

a r t i c l e i n f o a b s t r a c t

Article history: A large number of optimization strategies have been developed for semi-batch reactors (SBR) with a fixed
Received 29 June 2009 or free terminal time, with or without considering various sources of uncertainty. Such strategies account
Received in revised form 25 April 2010 for safety constraints rather empirically determined in the form of parameter thresholds, while safety
Accepted 5 May 2010
indices are seldom integrated in the optimization objective function. The present work illustrates how
Available online 13 May 2010
the runaway boundaries, and their confidence region associated to the parameter uncertainty, can be
evaluated using the process model and a generalized sensitivity criterion, and how they can be included
Keywords:
in the SBR optimization. A concrete example is provided for the SBR used for the acetoacetylation of
Semi-batch reactor
Optimization
pyrrole with diketene in homogeneous catalysis, a process known to be of high risk due to the very
Safety boundaries exothermic side-reactions. While previous studies approached the isothermal SBR, the present work is
Pyrrole focused on optimizing the non-isothermal SBR operation.
Diketene © 2010 Elsevier Ltd. All rights reserved.

1. Introduction
Optimal operation of a batch or a semi-batch reactor (SBR) is
a classical, but still of high interest problem due to several rea-
sons. On the one hand, it is the economic interest to increase the
plant productivity, the reactor being the main equipment on which
the optimization efforts are focused due to the high value of raw-
materials and products related to the production cost, but also due
to its high sensitivity to operating conditions affecting the prod-
uct quality and raising possible safety problems (Bonvin, 1998). On
the other hand, it is the current trend to move production of a lot
of chemicals from the stable continuous plants to multi-product
(semi-)batch reactors, as being more flexible and easily adaptable
to market requirements. If the chemical reaction exhibits a high
thermal effect, it is preferable to be conducted in a semi-batch
mode: one of the reactants is slowly added to the second com-
ponent, which has already been fully loaded to the reactor. Thus,
the evolution of the reactor temperature can be kept under con-
trol, while a certain optimal feeding policy can ensure production
maximization. An advanced control is usually implemented to keep
the reaction synthesis within defined safety limits and in an eco-
nomic operating region (Loeblein, Perkins, Srinivasan, & Bonvin,
1999). However, frequent perturbations in the operating parame-
ters, raw-materials and recycling conditions, catalyst replacement
or reactivity modifications, all require periodical updates of the SBR
∗ Corresponding author. Tel.: +40 744 830 308.
E-mail address: gmaria99m@hotmail.com (G. Maria).
operating policy and of technological and safety margins for the
operating variables/parameters.
In spite of being intensively investigated, derivation of the opti-
mal operating policy of a SBR remains a complex problem to be
solved for every particular case. As reviewed by Bonvin (1998),
there are several important aspects to be considered in formula-
tion of an optimization objective function: maximization of the SBR
productivity and product quality with using minimum necessary
raw-materials and utilities; fulfilment of safety requirements in the
case of highly exothermic primary (desirable) or secondary (unde-
sirable) reactions, possibly developing chain exothermic reactions
with gas production; fulfilment of the technological and ecological
constraints; scale-up the laboratory information to get a process
model and SBR optimal operating conditions; ensure a certain flex-
ibility of the SBR optimal operation, to become readily adaptable
to the available equipment in a multipurpose-plant and multi-
product development strategy.
Consequently, optimization of the SBR operation involves
multiple challenging issues to be considered: time-varying char-
acteristics of the process, due to the SBR way of operation, but
also from batch-to-batch due to adjacent unit operations, resulting
in a variability of raw- and recycled-material purity; nonlin-
ear characteristics of the process and heat transfer, difficult to
be precisely modelled; model inaccuracies coming from a large
variety of sources (experimental data quality, adopted simplifi-
catory hypotheses, material variability, identification procedure);
few available measurements, especially when frequent changes
in production are required; the presence of a large number of
technological, economical, ecological, and safety constraints to

0098-1354/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.compchemeng.2010.05.003
178 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189

Nomenclature
j stoichiometric coefficient of species j
Notations  liquid phase density
Ar , Ae , Am heat exchange surface of the reactor: Ar is mea-
standard deviation
sured inside the reactor; Ae is measured cooling fluid
2 variance
side; Am is the logarithmic mean between Ar and Ae  time constant
A Arrhenius frequency factor  ad induction time to explosion under adiabatic condi-
aj correlation coefficients in Eq. (2) tions
B = Tad E/(RTo2 ) reaction violence index D time of addition of co-reactant D
cj component j concentration
cp molar specific heat Superscripts
d distance ∧ estimated value
dr reactor inner diameter - average value
ds stirrer diameter * reference value
Da = (−A )(rA  D )/cA,o Damköhler number for SBR ∼ distribution
E activation energy
F feed flow-rate (liquid) Index
f model function vector a cooling agent
g path constraint function vector ad adiabatic
G terminal constraint function vector c critical
Hfo standard enthalpy of species formation f final
−H reaction enthalpy in inlet
he reactor convective heat transfer coefficient, on the l liquid phase
cooling agent side max maximum
hi heat transfer coefficient, on the reactor side min minimum
IHi the increments of structural groups i for enthalpy of o initial
formation in the Joback formula w referring to the reactor wall
k rate constants
nj species j number of moles Abbreviations
N normal distribution, or stirrer speed BR batch reactor
Ndiv number of equal divisions of the batch time tf D diketene
Pr Prandtl number DHA dehydroacetic acid
P probability FDM finite difference method
PN normal cumulative distribution function MINLP mixed-integer NLP
p overall pressure MV Morbidelli–Varma criterion
Qevap vaporization heat NC nominal conditions
R universal gas constant NLP nonlinear programming
Re Reynolds number P pyrrole
r chemical reaction rate PAA 2-acetoacetyl pyrrole
si the number of structural groups of type i (in the Py pyridine
chemical formula) SBR semi-batch reactor
s(y;) absolute sensitivity, ∂y(t)/∂ STD standard deviation
S(y;) normalized sensitivity, (∗ /y∗ )s(y; )
St = (U Ar D )/(V ¯ c̄p ) Stanton number for SBR
t time
be considered with a certain weight in order to obtain the best
tf final batch time
operating solution (compromise); presence of disturbances in the
T temperature
operating parameters making accurate implementation of the opti-
Tad temperature rise under adiabatic conditions
mal policy questionable; limited on-line corrective actions due to
TMRad time-to-maximum-rate under adiabatic conditions
the finite duration of a (semi-)batch.
U overall heat transfer coefficient
Optimal operation of a SBR is usually focused on deriving an
u manipulated variable vector
optimal feeding policy for the co-reactant and, sometimes, an
V liquid (reactor) volume
optimal temperature dynamic profile to be realized in the reac-
x, y state variable vector, or dependent variables
tor, by usually manipulating one or two input variables. In all
w penalization weights in the Lagrange function
alternatives, the optimal policy for a fixed or free terminal batch
time results from the minimization of an objective function in the
Greek symbols
presence of problem constraints. If known, the sources of uncer-
 finite difference
tainty and its characteristics can be included during optimization,
ı random variation
leading to a certain degree of the problem solution uncertainty.
ıt reactor wall thickness
As a consequence, various procedures have been developed for
˚ optimization objective function
the model-based SBR optimization (Abel & Marquardt, 2003;
 operating parameter vector
Kadam, Schlegel, Srinivasan, Bonvin, & Marquardt, 2007; Rahman &
t ,  thermal conductivity of the reactor material; ther-
Palanki, 1996; Srinivasan, Palanki, & Bonvin, 2002, 2003; Terwiesch,
mal conductivity
Agarwal, & Rippin, 1994): robust (off-line) one-time optimization
dynamic viscosity
without (nominal) or with considering the parameter uncertainty,
and using the off-line derived process model; optimization of the
 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189
expected value of the objective function under uncertainty; batch-
to-batch optimization using a model updating step and additional
information from past batches (the so-called ‘tendency modelling’);
on-line SBR optimization, the solution being adapted based on
the acquired on-line information from the process and used to
improve the model adequacy and the operating policy for the rest
of the batch. All these formulations are solved using various nonlin-
ear programming (NLP) or mixed-integer NLP (MINLP) numerical
solvers due to the presence of a large number of constraints.
The safety requirements, especially for highly thermal sensitive
BRs or SBRs, are usually considered during the reactor optimiza-
tion as explicit constraints (many times empirically determined
from observations and past experience with the process), by tak-
ing certain levels of state sensitivity functions as constraints (Chen,
Erickson, & Fan, 1970; Seinfeld & McBride, 1970), or by keeping a
certain distance from the runaway boundaries due to the uncer-
tainty in the operating parameters (Mönnigmann & Marquardt,
2003; Takamatsu, Hashimoto, & Ohno, 1970; Watanabe, Nishimura,
& Matsubara, 1973; Wen & Chang, 1968). Recent developments
check safety constraints in the form of scenario-integrated path
constraints, via repeated (time-consuming) simulations over a cer-
tain time horizon (Abel & Marquardt, 2003). All such strategies
suffer from the lack of a systematic and precise model-based deriva-
tion of the safety limits of the operating region to be considered
during SBR optimization.
In the homogeneous reaction case, the accumulation of the co-
reactant is possible at low temperatures due to the reduced reaction
rates. As a consequence, a sudden increase in the reaction tem-
perature leads to an exponential rise in the reaction rates (when
the co-reactant is in large amounts), which in turn will lead to a
continuous rise in the reactor temperature up to conditions when
the cooling system becomes ineffective, eventually determining
the reactor explosion. The situation is worsened by the occurrence
of exothermic chain/polymerization reactions that lead to a quick
increase in temperature or pressure with eventually the same effect
(Grewer, 1994; Stoessel, 2008; Varma, Morbidelli, & Wu, 1999).
Conditions for runaway in the heterogeneous liquid–liquid systems
are also given in the literature (Westerterp & Molga, 2004).
The scope of this paper is to investigate the advantages of using a
more elaborated and general strategy to evaluate the SBR runaway
boundaries for a known process, to be considered when deriving
the optimal operating policy in the presence of parameter uncer-
tainty. Past researches suggested keeping the optimization solution
inside the random variation region of parameters that never inter-
sects the safety boundaries (Mönnigmann & Marquardt, 2003).
Our investigations suggest also considering the runaway bound-
ary uncertainty when optimizing the SBR, by keeping the optimal
solution outside the confidence region of the runaway boundaries.
Such a solution corresponds to a minimum probability to inter-
sect the safety limits for an assumed confidence level, and for an
adopted weight of the safety constraint in the objective function. To
derive the SBR thermal runaway conditions, the generalized sen-
sitivity criterion of Morbidelli and Varma (MV; Varma et al., 1999)
has been used, as being generally applicable irrespectively to the
kinetics or reactor complexity. As another element of novelty, an
adequate algebraic correlation of the critical conditions with the
operating parameters has been derived, valid over the considered
operating region. Such a simple correlation allows simplifying the
SBR optimization steps including probabilistic evaluations.
The examined SBR is the bench-scale jacketed reactor for the
acetoacetylation of pyrrole (P) with diketene (D) in homogeneous
liquid phase, used by Ruppen, Bonvin, & Rippin (1997) to identify
the optimal isothermal feeding policies that maintain the reactor
within technological limits and lead to an acceptable PAA prod-
uct yield. Several other authors investigated this SBR to derive
an optimal feeding policy under isothermal conditions, without
179
considering any systematically derived safety constraint. In the
present study, the optimal feeding policy with diketene solution
will be obtained under non-isothermal conditions, including safety
requirements explicitly, in the probabilistic sense. Besides, both the
solution-feeding rate, and its concentration will be considered as
optimization variables, leading to an increased SBR flexibility.
The developed computing methodology can be easily extended
to optimization of other SBRs of industrial interest, by realizing a
satisfactory compromise between the productivity/low-cost goal
and safety requirements.
2. Process characteristics, reaction hazard, and semi-batch
reactor model
The acetoacetylation of pyrrole with diketene in homogeneous
liquid phase (toluene), at around 50 ◦ C and normal pressure, hav-
ing pyridine as catalyst, is a common method for producing pyrrole
derivates, such as 2-acetoacetyl pyrrole (PAA) used in the drug
industry. The process is of high thermal risk due to the tendency
of very reactive diketene to polymerize at temperatures higher
than 60–70 ◦ C, or in the presence of impurities that can initiate
highly exothermic side-reactions difficult to be controlled (Nakano,
Kosaka, Hiyama, & Nozaki, 2003). A few number of investigations
on the process kinetics have been reported, the most relevant being
the study of Ruppen et al. (1997) in a bench-scale isothermal SBR
operated at 50 ◦ C using a high excess of toluene as solvent.
Due to such reasons, the reaction at industrial scale is con-
ducted in a semi-batch mode: the solution of diketene in toluene is
slowly added to the reactor, initially loaded with solution of pyrrole
in toluene (recovered from previous batches and including some
impurities). In principle, the evolution of the reactor temperature
can be kept under control by adjusting the feeding rate and cool-
ing regime, while a certain feeding policy can ensure production
maximization. Although optimal operating conditions can be deter-
mined from lab-scale experiments, operation of the industrial SBR
is however difficult. Small variations in the catalyst characteristics,
raw-material or solvent quality, a sudden increase in temperature
due to fluctuations in the cooling system performance, or an accu-
mulation of reactive diketene favour secondary reactions of risk.
Such variations significantly change the selectivity between the
desired and undesired products, and therefore lead to also signifi-
cant variations in the product quality from batch-to-batch.
The reaction scheme advanced by Ruppen et al. (1997) includes
four main steps presented in Table 1. The synthesis of the desired
PAA product is accompanied by several side-reactions of diketene,
leading to the dimmer DHA, oligomers Dn , or PAA derivatives
denoted by G (the intermediate reaction of diketene with DHA has
been neglected from the model). The co-reactant diketene presents
an extreme reactivity and hazardous properties, as revealed by
existing databases. Because of that, the temperature regime must
be strictly controlled and diketene concentration in the reactor
kept lower than a certain critical threshold (ca. 0.025 mol L−1 ,
empirically determined; Ruppen et al., 1997; Martínez, 2005).
The kinetic model considers only first or second-order reactions,
with the rate constants evaluated by Ruppen et al. (1997) at
nominal operating conditions of 50 ◦ C and [PAA] > 0.1 M. Due to
incomplete experiments, an activation energy of E/R = 10,242 K was
adopted in this paper for all reactions of diketene, by analogy
with the diketene derivate polymerization (Sato, Morita, Tanaka,
& Ota, 2003), and with the initiation energy of olefin polymer-
ization (Lenz, 1967). The resulted Arrhenius constants (Ai , Ei ) are
displayed in Table 1. All reactions are moderately exothermic,
excepting the diketene oligomerization of standard heat around
−340 kcal mol−1 (for an n = 10–12 degree of oligomerization, see
footnote of Table 1).
180 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189

Table 1
Reaction schema, kinetic model, and some hazard indices of the process (Notations: D = diketene; P = pyrrole; PAA = 2-acetoacetyl pyrrole; DHA = dehydroacetic acid;
Py = pyridine).

Reaction, rate expression Arrhenius constants A Reaction enthalpy Tad (K)c B indexd TMRad (min)e Daf Da/Stg
(L mol−1 min−1 ; min−1 ) E/R (K)a (kcal mol−1 )b
ka ,Py
P + D −→PAA Aa = 3.1324 × 1012 Ha = −31.70 61.8 6.07 3.57 7.1 × 107 4.6 × 105
ra = ka [P][D] Ea /R = 10,242.4
b k ,Py
D + D −→DHA Ab = 7.5651 × 1012 Hb = −21.96 5.3 0.52 3.95 1.7 0.01
2
rb = kb [D] Eb /R = 10,242.4
kc
nD−→(D)n Ac = 1.6549 × 1012 Hc = −340.69 83.0 8.15 4.75 4.2 0.03
rc = kc [D] Ec /R = 10,242.4
dk ,Py
PAA + D −→G Ad = 1.7731 × 1012 Hd = −31.70 7.7 0.76 4.21 4.5 × 106 2.9 × 104
rd = kd [PAA][D] Ea /R = 10,242.4
a
k = A × exp(−E/RT ). Lacking of kinetic data, the activation energy has been adopted the same for all reactions, corresponding to that of diketene derivate polymerization
(Sato et al., 2003), being in the same range with the free-radical polymerization of olefins (Lenz, 1967). Rate constants at 50 ◦ C are (Lee et al., 2001): ka = 0.053; kb = 0.128;
kc = 0.028; kd = 0.003 (all in L mol−1 min−1 , excepting kc in min−1 ). Rate constants increase with the medium polarity (not accounted here), the reported values being valid for
[PAA] > 0.1 mol L−1 (Ruppen et al., 1997). Other secondary reactions (such as DHA + D → G ) have been neglected.
b
Ha was derived from species Hfo (Jolkkonen, 2000). Hb was taken from Lopatin, Popov, Epshtein, Mikhaleva, & Makarov (1992). Hc was derived using the standard
-1
Hfo = −897.5 kcal mol of diketene oligomer Dn , corresponding to a n = 10 cyclic oligomer or a n = 12 acyclic (Nakano et al., 2003), and evaluated by means of Joback’s

formula (Reid, Prausnitz, & Poling, 1987): Hfo = 68.29 + si IHi (kJ mol−1 ), where si = the number of structural groups of type i; IHi = the increments of structural groups i
for enthalpy of formation. Hd was adopted at the same value with Ha .
c
Tad = (−H)cj,o /(l cp,l ) = temperature rise of the reaction mixture under adiabatic conditions (Froment & Bischoff, 1990), where cj,o = initial concentration of key
species; l = liquid mixture density; cp,l = specific heat of the liquid mixture.
d
B = Tad E/(RTo2 ) = reaction violence index (Grewer, 1994; Maria, 2007), where To = initial temperature of the reaction. Values of B > 5 indicate hazardous reactions, of
high risk.
e
TMRad = time-to-maximum-rate under adiabatic conditions, obtained by reactor simulations.
f
Da = D /1 = (−A )(rA D )/cA,o = Damköhler number; St = (U Ar D )/(V ¯ c̄p ) = Stanton number for SBR. Slow reactions correspond to Da < 50–100 and Da/St < 1
(Grewer, 1994). These numbers are evaluated at initial SBR conditions.

To quickly assess the hazard of reactions (kinetic and ther- the so-called exothermicity, reactivity and cooling numbers, that
modynamic), some probability, severity and criticality indices for combine influences of various parameters leading to operation
runaway scenario in SBR can be used, critical operating condi- within a critical region (Westerterp & Molga, 2004).
tions being defined by simple inequalities (Grewer, 1994; Hugo Application of such a quick hazard assessment in the present
& Steinbach, 1986; Maria & Heinzle, 1998; Shah, Fischer, & case study reveals that reactions #1–3 (and especially #3,
Hungerbühler, 2003, 2005): the oligomerization of diketene) from Table 1 are potentially
−1
TMRad = t|r=rmax < 8h; ad = (ko B) (probability indices)
(−H)cj,o Tad E
Tad = > 50 K, B= >5 (severity indices)
¯ c̄p RTo2
D (−A )rA D (1)
Da = = < 50 − 100 (criticality index for slow reactions vs. addition time)
1 cA,o
Da U Ar D
< 1, St = (combined criticality index)
St V ¯ c̄p

where TMRad = time-to-maximum-rate under adiabatic
conditions;  ad = adiabatic induction time to explosion;
B = reaction violence index; Tad = adiabatic temperature rise;
Da = Damköhler number for the key reactant A (start material);
St = Stanton number; cj ,o = initial concentration of key species;
¯ = reacting mixture density; c̄p = average specific heat;
To = initial temperature of the reaction; R = universal gas con-
stant; t = reaction time;  D = time of addition of the co-reactant;
 l = reaction time constant, e.g. 1/ko for the first-order reaction,
and 1/(ko cBo ) for the second-order reaction between A and B at
small conversions; ko = reaction rate constant at the cooling tem-
perature T˛ ; U = heat transfer coefficient; Ar = heat transfer area;
V = reactor volume; −A = stoichiometric coefficient of reactant
A. Indices’ values overstepping the recommended thresholds
indicate potential dangerous reactions, presenting a fast evolution
and significant exothermicity. It should be noted that SBR safety
conditions are related not only to how fast and exothermic the
reactions are, but also to their dynamics in relationship with the
rate of addition of the co-reactant. The mentioned approximate
methods based on simple engineering numbers can only give a
rough idea about unsafe operating conditions. For heterogeneous
SBR, similar runaway conditions can be derived by accounting for
dangerous even under the nominal initial operating condi-
tions mentioned in Table 2. Thus, Tad = 62 K (reaction #1) and
Tad = 83 K (reaction #3) are larger than the threshold 50 K; B = 6
(reaction #1) and B = 8.1 (reaction #3) are larger than the thresh-
old 5; Da = 1.7 (reaction #2) and Da = 4.2 (reaction #3) are smaller
than the threshold 50–100 (slow reactions); avg. TMRad ≈ 4 min
is much smaller than the 8 h threshold; Da/St = 0.01 (reaction #2)
and Da/St = 0.03 (reaction #3) are much smaller than the thresh-
old 1. Consequently, reactions #1–3 display a high thermodynamic
and kinetic hazard, being susceptible to runaway at higher tem-
peratures if diketene is present in large amounts. The adiabatic
induction time to explosion of  ad = (ko B)−1 ≈ 4 min for reaction
#3 (Grewer, 1994) confirms the conclusion that oligomerization
of diketene is the most dangerous reaction for this process.
To make quick estimations of the critical conditions and optimal
operating policy, a simple SBR model was adopted, correspond-
ing to a perfectly mixed vessel, with no mass and heat transfer
resistances in the liquid (Froment & Bischoff, 1990). The solution
of diketene is continuously added with a constant/variable fed
flow-rate F(t) over the continuously stirred pyrrole solution (of
known initial composition, including impurities coming from pre-
vious batches). The cooling agent circulating in the reactor jacket
 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189 181

Table 2
Semi-batch reactor model, nominal operating conditions, technological and safety constraints (D = diketene; P = pyrrole; PAA = 2-acetoacetyl pyrrole; DHA = dehydroacetic
acid).

Observations

Differential balance equations

Species mass balance: At t = 0: cj = cj,o ;T = To
dcD
dt
= (−r̃a − 2r̃b − r̃c − r̃d ) + (cD,in − cD ) VF(t)
(t)
;
dcP dcPAA
dt
= −r̃a − cP VF(t)
(t)
; dt = (r̃a − r̃d ) − cPAA VF(t)
(t)
;
dcDHA F(t) dV
dt
= r̃ b − cDHA V (t)
; volume variation: dt
= F(t);
Reaction rate correction with the catalyst dillution: rc is not corrected with the catalyst dillution, the reaction
r̃j = rj VV(t)
o
; j = a, b,d displaying another mechanism (the stoichiometric
 coefficient was included in the rate constant)
(−Hj ) r̃j V (t)−UAr (T −Ta )
dT F(t)(Tin −T ) j
Heat balance: dt
= V (t)
+ ¯ c̄p V (t)
,
j = a, b,c, d
Model hypotheses
Semi-batch reactor model with perfect mixing and
uniform concentration and temperature field
 dr2 4
Cyllindrical reactor of variable liquid volume and heat Ar = 4
+ dr
V (t)
transfer area.
Heat transfer coefficient computed with the formula: ReN = (ds2 N )/
¯ ¯
ıt Ar hi dr

0.14
1
= 1
+ + 1 Ar
; = 0.36 Re0.66 Pr 0.33
Pr = (c̄p )/
¯  ¯
U hi t Am he Ae ¯ N w
(approximate value for nominal conditions is
U = 500 kcal m−2 h−1 K−1 )
Heat of solvent vaporization in the reactor is neglected Qevap ≈ 0
Heat capacity and density of fed solution are the same with ¯ in c̄p,in ≈ ¯ c̄p
those of reactor content.
Nominal operating conditions and range of variationa
Initial liquid volume (Vo , L) 1 Initial [PAA] (mol L−1 ) 0.08 ≤ 0.10 ≤ 0.20
Reactor inner diameter (dr , m) 0.1 Initial [DHA] (mol L−1 ) 0.01 ≤ 0.02 ≤ 0.04
Stirrer speed (N, rot. min−1 ) 640 Fed D-solution flow-rate (F ×100, L min−1 ) 0.05 ≤ 0.15 ≤ 0.20
Liquid physical properties: toluene solvent Batch time (tf , min): 120 ≤ 145 ≤ 378
−1
Inlet [D] (mol L ) 4 ≤ 5.82 ≤ 6 Initial temperature (To , ◦ C) 40 ≤ 50 ≤ 60
−1
Initial [P] (mol L ) 0.4 ≤ 0.72 ≤ 0.8 Cooling agent temperature (Ta , ◦ C) 50
Initial [D] (mol L−1 ) 0.005 ≤ 0.09 ≤ 0.14 Feeding solution (Tin , ◦ C) 50

Process constraint expression Significance

G1 = cDHA,f − 0.15 ≤ 0 (mol L−1 ) Prevent precipitation of DHA at room temperature
(solubility at 50 ◦ C is 0.20 mol L−1 )b
G2 = cD,f − 0.025 ≤ 0 (mol L−1 ) Avoid high concentrations of toxic D in productb ; empirical
critical runaway conditionc
g1 = Max(T (t)) − 70 ≤ 0 (T, ◦ C) Prevent toluene solvent excessive vaporization, pressure
  increase, and dangereous exothermic side-reactionsd
¯
2 )
g2 = g2,j , g2,j = Min P(Fj (t) > Fc ), j = 1, ..., Ndiv ; Fc ∼N(F̄c (), Prevent rapproachemets of all arc input variables Fj on the
F c
Fc runaway boundary under random variations of process
parameters j e
g3 = Da − 100 > 0 Thermal safety critical index in SBR for slow reactionsf
g4 = Da/St − 1 < 0 Thermal safety critical index in SBR for slow reactions and
improper cooling systemg
a
Brendel, Mhamdi, Bonvin, & Marquardt (2003); Martínez (2005); Lee et al. (2001). Operating conditions are varied for ensuring the maximum productivity of the reactor,
i.e. Max PAA yield (nPAA,f /np,o ), or Max P production (nPAA,f = cPAA,f Vf ) (Lee et al., 2001; Loeblein et al., 1997; Martínez, 2005; Ruppen et al., 1997; Srinivasan & Bonvin, 2003).
b
Ruppen et al. (1997).
c
Martínez (2005).
d
Empirically predicted by adding 2 × Tc = 20 K to the nominal temperature, where Tc = RTo2 /E corresponds to the critical conditions of Semenov for zero-order reactions
(Varma et al., 1999; Maria, 2007).
e
For normal distributed random variations of the (uncorrelated) operating parameters around nominal conditions j ∼N( ¯ j ,
 ), the approximate variance of critical
 2 j

Fc can be evaluated using the error propagation formula:

F2 = ∂Fc /∂j
2 (Park & Himmelblau, 1980). Thus, for every batch time arc the constraint becomes:
c j

  j
 
g2,j = Min 1 − PN (Fc − dj < Fc < Fc + dj ) , j = 1, ..., Ndiv , for a given distance from the running to the critical conditions, dj = Fj () − Fc (), and for Fc ∼N(F̄c (),
¯
2 ).
F c
D (−D )rD D
f
The Damköhler number Da = 1
= cD,o
is evaluated for the co-reactant D, where (−D ) = stoichiometric coefficient of D reactant;  D = time of addition of the
co-reactant;  1 = reaction time constant (Grewer, 1994).
UA 
g
The Stanton number St = V ¯r c̄pD is evaluated for the co-reactant D (Grewer, 1994).

continuously removes the reaction heat. The mass and heat bal- been approximated to those of the toluene solvent, and a constant
ance equations, presented in Table 2, explicitly account for the overall heat transfer coefficient has been adopted (evaluated at
liquid volume (and heat transfer area) variation due to the added nominal conditions with the formula from Table 2). The reactor
diketene solution. The continuous catalyst dilution is accounted for model has been solved with a common low order stiff differential
when correcting the reaction rates, excepting for reaction #3 pre- equation integrator.
sumed to be promoted not by pyridine, but by some impurities The characteristics of the reactor, the nominal operating condi-
(of quasi-constant total concentration). To speed-up the computa- tions, and operating parameter ranges reported by various authors
tional steps, the physical properties of the reaction mixture have under isothermal conditions are presented in Table 2. Parameter
182 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189
Fig. 1. (Left, centre) Evolution of the reactor temperature, P-conversion, and PAA yield over the batch time under nominal conditions (NC, Ta = To = 323 K, see Table 2). The
curve indices correspond to constant feed flow-rates of: F = 0.0015 L min−1 (1); F = 0.0050 L min−1 (2); F = 0.0085 L min−1 (3); F = 0.0090 L min−1 (4). (Right) Dynamics of the
temperature and its sensitivity function S(T ; F)/2000 during the batch time, for two inlet flow-rates (F = 0.0010 L min−1 , and F = 0.0084 L min−1 ).
ranges are determined experimentally or by simulation to fulfil
the technological constraints G1 and G2 derived from empirical
observations on safe operating conditions. Consequently, an opti-
mal feeding policy and a tight control of the reactor temperature
are necessary to simultaneously fulfil all the productivity and safety
requirements.
3. Derivation of SBR runaway boundaries and their
confidence region
Runaway and eventual explosion of a SBR may occur when
the rate of heat generation becomes higher than the rate of heat
removal by the cooling system. Model-based accurate evaluation
of the safe operating region that exhibits low thermal sensitivities,
by setting the runaway boundaries in the parametric space, is not an
easy task. That is because of the computative numerical algorithms
to be applied, but also due to fluctuations in the characteristics of
the process, catalyst, impurities and raw-materials, thus requiring
periodic process model updating (Fotopoulos, Georgakis, & Stenger,
1994; Maria, Terwiesch, & Rippin, 1996; Ruppen et al., 1997), and
consequently an update of the runaway boundaries themselves.
Among alternatives, a sensitivity method has been applied
in this paper to evaluate the runaway boundaries in the oper-
ating parametric space. Such methods are based on evaluation
of the sensitivity function of a state variable y with respect
to a parameter , i.e. s(y; )t = ∂y(t)/∂ (in absolute terms), or
S(y; )t = (∗ /y∗ )s(y; )t (in relative terms; * = nominal operat-
ing point in the parametric space). Unsafe conditions correspond
to a sensitive operation when “the reactor performance becomes
unreliable and changes sharply with small variations in param-
eters” (Varma et al., 1999). The time-dependent state sensitivity
functions s(y; )t = ∂y(t)/∂ (i.e. of temperature, conversion, selec-
tivity, species concentrations, pressure) vs. process parameters (i.e.
j = [To , Ta , cjo , cj,in , po , B, U, . . .]) are computed by means of a sen-
sitivity differential equation solved simultaneously with the reactor
dynamic model (Varma et al., 1999). Of most interest in SBR hazard
assessment is the sensitivity of the reactor temperature hot spot
Tpeak = (Tmax − To ) or Tmax during the batch operation, i.e. S(Tmax ;
). Detection of the operating regions, where certain combinations
of parameters lead to a high thermal sensitivity of the SBR, offers
the possibility to accurately set the safety limits of the operating
region. Thus, the generalized sensitivity criterion of thermal run-
away of Morbidelli and Varma (MV; Varma et al., 1999) has been
used in the present study, as being applicable to complex reactions
irrespectively to the reactor type. According to the MV criterion,
the hot spot (Tmax − To ) induces a sharp increase of the normalized
sensitivity S(Tmax ; ) under critical conditions, independently of the
considered operating parameter (e.g. To ,cj,o , Fin , Ta , B, Da, St,. . ., or
a combination of them). Thus, critical conditions
 correspond
  to the
maximum of the absolute value of s(Tmax ; ), or S(Tmax ; ). Eval-
uations of s(y; )t = ∂y(t)/∂ derivatives have been performed in
the present study by means of finite difference numerical method
(FDM), even if its accuracy is computationally costly, because it
requires small discretization steps near critical conditions.
To precisely determine the runaway boundaries of the operating
parameters  with the MV-method, it is necessary to investigate
first the regions in which the state variables, and especially the
reactor temperature, exhibit high sensitivities to the operating con-
ditions, even if such set points will not be later used as nominal
operating conditions. By successively perturbing the main operat-
ing parameters around the nominal conditions, the most influential
variables of the process can be roughly established. Then, moving
the set point in a more sensitive region and performing repeated
simulations of the reactor dynamics, critical conditions for the oper-
ating variables in the parametric space can be obtained (Maria &
Stefan, 2010).
To determine where the sensitive operating region is located, it
is enough to check by simulation the SBR state variable dynamics
for various parameter values. Simulations for nominal conditions
(cD,in = 5.82 M) and constant F during the batch in the range of
F ∈ [0.0015–0.0090] L min−1 are presented in Fig. 1 (left and cen-
tre). The plotted dynamics of the reactor temperature, P-conversion
and PAA yield, together with the dynamics of reaction rates, reac-
tion Damköhler (Da) or Damköhler/Stanton (Da/St) numbers (not
plotted here) offer a first guess of the operating region of high ther-
mal sensitivity. For instance, starting with F = 0.0085 L min−1 , the
temperature T(t) profile not only exhibits values higher than the
critical threshold of 70 ◦ C (g1 from Table 2), but the curve tends
to oscillate. Higher fed flow-rates produce amplification of oscil-
lations, toluene vaporization, a dangerous pressure increase, and
eventually the reactor runaway.
Such an effect can be explained by the slow secondary reac-
tions #2–3 which become dangerous when the co-reactant D is
accumulating at low temperatures. For small F-levels, the main
reaction consumes the co-reactant, the side-reactions are negli-
gible, and the temperature raise is small. For high F-levels, the
slow side-reactions lead to the co-reactant D accumulation. Conse-
quently, the increased rates of side-reactions will start to generate
more energy that will increase the reactor temperature. In turn,
a high temperature will lead to an increase of all reaction rates,
and to a rapid consumption of the D co-reactant. Depletion of D
will slow-down the reaction rates and will diminish the generated
 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189
Fig. 2. Runaway boundary curve (—) in the [F− vs.−Ta ] parametric plane depends on the chosen operating conditions: (Left) evaluation for cP,o = 1 mol L−1 , cD,in = 5.82 mol L−1 ;
(Right) evaluation for cP,o = 0.72 mol L−1 , cD,in = 7.5 mol L−1 (other parameters are set to the nominal values). The confidence band (—) of risk curves corresponds to the random
deviations of Ta ± ıTa with ıTa = 3 K.
heat leading to a temperature decrease. At low temperatures, the
accumulation of the co-reactant is again possible due to the slow
reaction rates (Fig. 1) and the temperature will start to rise again.
The result is a continuous oscillation of the reaction temperature
and D-concentration in the reactor, with larger amplitudes as the
F-level is higher. When exceeding a certain critical Fc value, the
temperature oscillations are higher than a tolerable limit, leading
to process escalation and eventually explosion, since the cooling
system cannot remove the heat at the same rate.
The same analysis has been conducted by successively vary-
ing the cooling agent temperature Ta ∈ [40–60] ◦ C, the initial
temperature To ∈ [20–60] ◦ C, the diketene solution concentration
cD,in ∈ [4–7.5] mol L−1 , and the initial concentration of pyrrole
cP,o ∈ [0.4–1] mol L−1 . By comparing the results, one can conclude
that the most influential variables for the process safety are  = [F,
Ta , cD,in , cP ,o ]. The batch initial temperature presents a small influ-
ence on the reactor dynamics, while small variations of the initial
concentrations for other species than pyrrole do not present a high
interest.
To precisely determine the runaway boundaries in every F vs.
j plane (denoted as F−j ), by keeping nominal states for all other
parameters, the time-dependent temperature sensitivity functions
have been evaluated by replacing the derivatives with finite differ-
ences s(T ; j )t = T (t)/j , and performing repeated simulations
under various operating conditions. The time discretization step
has been set very small (tf /5000) to consider all temperature peaks
in the critical operating region, and a small discretization step
has been used in evaluating the sensitivity functions, i.e. (max −
min )/n, with n = 200–500. The dynamics of such a relative sensi-
tivity function is displayed in Fig. 1 (right) for two extreme values
of the feeding flow-rate F-levels. Of interest is only the sensitiv-
ity of the temperature maximum vs. the control variable, that is
S(Tmax ; F), or S(Tmax ; FD,in ).
Let us consider repeated simulations of the SBR dynamics for
various F-levels, for a chosen operating parameter j (e.g. Ta ), by
retaining the obtained relative  S(Tmax ;F) curve. It is to observe
that a sharp increase in the S(Tmax ; F) is recorded for a certain
F exceeding a critical value F > Fc . Calculations are then repeated for
another j value, and retaining every time the corresponding Fc .
Critical values Fc (j ) determined in this way are then represented
in the [Fc vs. j ] plane. The runaway boundary divides the plane into
two regions, corresponding to a safe or an unsafe operation of the
SBR (see Fig. 2). The procedure is repeated by choosing every time
j , a 95% confidence level for ıj =
another operating parameter j (e.g. cD,in , cP,o , or To ), by keeping
j , etc.). For instance, the resulted confidence band of Fc (Ta ) for
nominal values for all other parameters, and deriving the corre-
sponding runaway boundaries Fc (j ) in separate planes (graphs not
183
presented here). It should be observed that critical values of feed-
ing rates Fc () depend on the operating parameter vector  = [F,
Ta , cD,in , cP ,o, To ] around which evaluation is made. For instance, in
Fig. 2 the runaway boundaries in the F−Ta plane have been obtained
for two different operating conditions corresponding to high cD,in
and cP,o levels. As expected, Fc decreases as the operating severity
increases, corresponding to high Ta temperatures, large cD,in , and
small cP,o concentrations. As the Fc (To ) is roughly parallel to the To
abscissa, it results that initial batch temperature has little influence
on the critical Fc over the investigated parameter domain.
The manipulated inlet variable is the molar feeding rate with
D co-reactant, that is the product FD,in,c = (FcD,in )c . Keeping in mind
that all calculations of critical Fc have been done for a constant
cD,in = 5.82 mol L−1 (nominal value), extension of the validity of the
runaway boundary plots can be easily performed by replacing the
Fc ordinate with the product (5.82 Fc ) moles D min−1 . Thus, the esti-
mated boundary curve diagrams can be used for checking operation
at various feeding solution concentrations.
Bringing together all these runaway limit curves in various
parameter planes determined over the whole parametric space
Fc (j ), it is possible to obtain the global sensitivity of the reactor
by accounting for concomitant variations of several input/process
parameters. An empirical algebraic correlation Fc (), of logarithmic
type, has been found to adequately represent the critical reactor
conditions vs. the most influential operating parameters, of the
form:

3
Ln(F̂c ) = ao + aj Ln(j ), with  = [Ta , cD,in , cP,o ], (2)
j=1
Estimated regression coefficients a = [26.6766425, −5.1050358,
−1.05356372, 0.186367982] from a large number of preliminary
evaluations of critical conditions correspond to a satisfactory model
low standard deviation (8.9 × 10−5 L min−1 for the predicted F̂c ), the
relative residuals being small (avg. 4.4%) and alternatively positive
and negative (Maria, 2004).
Uncertainty of type  ¯ j ± ıj can be included in evaluation of
the confidence region of the runaway boundaries Fc ± ıFc . The
confidence band in the parametric plane corresponds to a 100% con-
fidence level if random fluctuations of parameters are uniformly
distributed, or to a lower confidence level for normal distributed
parameters depending on the distribution characteristics (i.e. a
68% confidence level for ıj =
2
ıTa = 3 K is presented in Fig. 2 (with dotted lines). Using the regres-
sion model F̂c (), approximate estimation of Fc variance (denoted
184 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189
by
F2c ) can be obtained using the error propagation formula for the
assumed uncorrelated parameters (Park & Himmelblau, 1980):
 ∂Fc
2
1997); results indicate Ndiv = 8, tf = 138.62 min, nPAA,f = 0.4409
a21 a22 a23
F2c =
2 = Fc2
2 +
2 Ta
T2a +
T2a . (3)
∂j ¯
j Ta 2
cD,in 2
cP,o
j 
Critical conditions and their associated uncertainty must be
considered in all studies dealing with determining the optimal
operating policy of the SBR. Since in many cases the most severe
running conditions correspond to a higher productivity, such a
running solution is expected to offer a higher degree of safety in
operation, with the expense of supplementary computational steps
with MV-method to derive the confidence of the safety limits.
4. Optimization problem formulation and safety
constraints
4.1. Problem formulation and past results
Derivation of an optimal running policy for a SBR consists in
determining the manipulated variable vector u, and sometimes of
the final batch time tf , from minimization of a suitable objective
function:
(û, t̂f ) = arg Min ˚(x, u, , tf )
s.t. ẋ = f (x, u, , t), x(to ) = xo (process dynamic model)
(4)
g(x, u, , t) ≤ 0 (path constraints)
G(x(tf ), ) ≤ 0 (terminal constraints)
where  = operating parameter vector; x = state variable vector. The
uncertainty of the solution comes from various sources: (i) model
uncertainty in both structure and parameters due to the avail-
able data uncertainty; (ii) operating parameter uncertainty due to
random disturbances ı␾; (iii) constraint uncertainty ıg,ıG due to
their simplified formulation and uncertainty of other variables; (iv)
objective function uncertainty ı˚ due to uncertainty considered for
the variables and parameters.
For the approached case study, the manipulated variable con-
sidered for controlling the SBR temperature is FD,in (t) = F(t)cD,in (t).
However, practical implementation requires a separate treatment
of the feed flow-rate F(t) and inlet solution concentration cD,in (t),
offering a larger degree of freedom by manipulating two physi-
cal input variables. Besides, operation at low F(t) and high cD,in (t),
or at high F(t) and low cD,in (t), even if it might present certain
equivalence, can lead to different thermal regimes and production
flexibility as below proved.
Published trials to find the optimal feeding policy F(t) for this SBR
by several authors, reported various results for a constant inlet con-
centration of diketene solution in toluene (cD,in = 5.82 mol L−1 ) and
under isothermal operating conditions. In fact, the derived feeding
policy is given on time-intervals, obtained by dividing the batch
time tf in Ndiv equal parts (the so-called ‘arcs’; Kadam et al., 2007),
of length t = tf /Ndiv , where the reactor input is continuous and
differentiable. By considering constant feeding characteristics over
every such interval, that is constant Fi (t) and cD,in ,i (t), over ti−1 ≤ t <
ti , i = 1, . . . , Ndiv , ti = it (switching points), then an optimal pol-
icy [F1 , F2 , . . . , FNdiv ] (for constant cD,in ), or [FD,1 , FD,2 , . . . , FD,Ndiv ]
(for both flow-rate and cD,in adjustable) can be derived by maxi-
mizing the reactor performance index in the presence of various
technological and safety constraints.
The reported results have been obtained by minimizing tf
under constant cD,in = 5.82 mol L−1 , and constraints G1 and G2
of Table 2, by imposing a certain productivity threshold, i.e.
nPAA ,f = cPAA ,f Vf ≥ 0.42 mol (equivalent to 45% PAA net yield), as fol-
lows:
(a) propose Ndiv = 3–8, without including model updating (Lee,
Lee, Lee, & Park, 2001; Loeblein, Perkins, Srinivasan, & Bonvin,
moles, G1 being slightly violated;
(b) propose Ndiv = 4–8, with including rate constant updating steps
from on-line measured data (Maria et al., 1996; Srinivasan
& Bonvin, 2003); results indicate Ndiv = 7, tf = 378 min,
nPAA,f = 0.4305 moles, with constraint G1 violated (Ruppen
et al., 1997);
(c) maximization of PAA production, using Ndiv = 1, with find-
ing the optimal tf and F(t) (Martínez, 2005); results indicate
tf = 227.50 min, nPAA,f = 0.5045 moles, F(t) = 0.0012 L min−1 ;
(d) maximization of PAA production, using Ndiv = 2, by impos-
ing the supplementary constraint cDHA,f + cG,f < cmax ,
cmax = 0.15 mol L−1 (Srinivasan & Bonvin, 2003); results
indicate tf = 120.00 min, reaction #3 being neglected (only
constraint G1 is considered).
In solving the associated NLP problem, the constraints have
been integrated in the objective function as additive penalty func-
tions multiplied by certain weights, or as simple penalty barriers
added to ˚ for avoiding production of the undesired by-products.
The reported results given in literature (plots not presented here)
display zigzagging time-profiles for input F(t), usually declining
towards the batch end time. As expected, the SBR productivity
increases with the reaction time, but also the production of by-
products and the risk of violating the technological constraints. An
increased number of time-arcs leads to an improvement of the reac-
tor productivity, allowing a more flexible reactor feeding policy, but
requires a considerable additional computational effort.
Reported optimization solutions suffer from several major
drawbacks: (i) they do not consider the temperature dynamics dur-
ing the batch (i.e. the energy differential balance of the reactor); (ii)
they do not consider a preliminary safety assessment step to pre-
cisely define the runaway boundaries in the parametric space, to be
considered during SBR optimization; (iii) they do not account for
the parameter or other source of uncertainty which can affect the
problem solution. Simple setting of safety constraints by means of
semi-empirical observations, or a rough evaluation using approxi-
mate explicit criteria is not enough to correctly set the search region
in the parameter space.
4.2. Derivation of optimal operating policies with/without
considering parameter uncertainty
To solve the SBR optimization problem in a more precise and
systematic way, several elements of novelty have been considered.
First, the non-isothermal thermal regime is explicitly considered
by means of the heat balance of the reactor, by also imposing to the
temperature to not overstep a threshold suggested by the Semenov
BR adiabatic runaway theory (the technological constraint g1 from
Table 2).
The compromise between the productivity/low-cost goal and
safety requirements, in the presence of parameter uncertainty, is
generally solved in literature either by minimizing a cost func-
tion with imposing a threshold for the failure probability, or by
minimizing the failure probability with imposing a threshold for
the cost/productivity requirements. In the present study, the first
alternative is adopted, by keeping the optimal solution outside the
confidence region of the runaway boundaries. Such a solution cor-
responds to a minimum probability of intersecting the safety limits
for an assumed confidence level.
For the fixed terminal time case, the SBR optimization criterion
has been formulated as an augmented objective Lagrange function,
 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189 185

of the form: (i.e. a 68% confidence level for ıFc =

Fc , or a 95% confidence level
[F1 , F2 , ..., FNdiv , cDin,1 , cDin,2 , ..., cDin,Ndiv ] = arg Max ˚(Fj , cD,in,j , ),
Fc ). Estimations of Fc () and
F2c are made in every iter-

Ndiv
˚ = wPAA nPAA,f − wG,1 G1 − wG,2 G2 − wg,1 g1 − wg,2
Ta = 3 K,
[D]in = 0.1 M,
j=1
[P]o = 0.05 M. It should also be mentioned that a more elabo-
s.t. Fj ≥ 0, cD,in,j ≥ 0, j = 1, ..., Ndiv .
By considering both input variables during the search, a higher
SBR flexibility is expected. The constraint functions are displayed
in Table 2.
Only parameter uncertainty is considered here, other uncer-
tainty sources being neglected. This is accounted for by including
the probability of violating safety limits by the running profile
[Fj ,cD,in,j ]. Thus, the constraint g2,j penalizes any rapprochement of
the tried arc flow-rate Fj () on the (known) runaway boundary
Fc (), in the probabilistic sense. By assuming a normal distribu-
tion for the parameter random fluctuations, ∼N(, ¯
2 ) (where  the same importance to the safety requirements and productivity

denotes the nominal point), a normal distribution of the runaway
¯
2 ). The
boundary Fc () can be assumed, of the form Fc ∼N(F̄c (),
Fc
constraint g2,j requires maximizing the distance dj from the run-
ning point to the critical conditions, which means minimizing the
probability that Fj ≥ Fc , i.e.:
 
g2,j = 1 − PN (Fc − dj < Fc < Fc + dj ) , (Minimum);
 
dj = Fj () − Fc () , j = 1, ..., Ndiv
where PN denotes the Normal cumulative distribution function of
the random variable. As small values for g2,j ≥ 0 are expected (usu-
ally in the range of 0–5%), such a policy tries to keep the operating
trajectory outside the confidence region of the critical conditions
for ıFc = 2
ation of the solution search, using the correlation models (2–3).
Normal fluctuations have been considered for the operating param-
g2,j
eters, with the standard deviations of
rated formulation of the optimization objective function in the
(5)
presence of multiple sources of uncertainty  will require comput-
ing the expected value of ˚, that is: ˚ = P()˚(FD,in (t, ), )d

(Terwiesch et al., 1994).
The chosen penalization weights in the objective function
depend on the relative importance given to each constraint. For
instance, by adopting the weighting factors wPAA = 1, wG,1 = 10,
wG,2 = 100, wg,1 = 0.1 for the technological constraints g1 , G1 –G2
one scales the variations of all terms of ˚ in the [0,1] range. As
the sum terms of constraints g2 represent failure probabilities for
every time-interval of the batch, a weighting factor wg,2 = 1 assigns
goal (wPAA = 1). In contrast, a small safety weighting factor, e.g.
wg,2 = 0.1, can be adopted when the productivity goal is preva-
lent, and the safety problems are not very stringent. The last choise
can be an option when the distance from the operating profile to
the runaway boundaries is large and an effective process control is
implemented on the SBR.
By solving Eq. (5), optimal molar feed flow-rates
[FD,1 , FD,2 , . . . , FD,Ndiv ] with D-solution are obtained. However,
(6)
practical implementation allows separate treatment of the feed
flow-rate F(t) and inlet solution concentration cD,in (t), offering a
larger degree of freedom. In fact, only a finite number of D feeding
solutions of known concentrations can be prepared before starting
the batch, such that the SBR feed might be switched during

Fig. 3. Optimal feed flow-rate policies [F(t), cD,in (t)], temperature profile, and PAA yield dynamics, for the semi-batch reactor for acetoacetylation of pyrrole. Optimal policies
ensure Max nPAA ,f using Ndiv = 8 feed flow-rate arcs, and fixed tf = 145 min, under the technological constraints g1 , G1 –G2 (Table 2), and without any safety constraint. The
checked operating conditions are the followings: (a) isothermal operation with constant cD,in = 5.82 mol L−1 , realizing nPAA ,f = 0.4358 moles (net PAA yield 0.4664); (b) non-
isothermal operation with constant cD,in = 5.82 mol L−1 , realizing nPAA ,f = 0.4708 moles (net PAA yield 0.5150); (c) non-isothermal operation with optimal found cD,in = 3 mol L−1
(derived from cD,in ∈ [3,4,5,6] mol L−1 possibilities), realizing nPAA ,f = 0.4820 moles (net PAA yield 0.5305).
186 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189

operation according to a certain policy. In the present study,
feeding solutions of concentrations cD,in,j ∈ [3,4,5,6] mol L−1 have
been considered. An effective MINLP procedure was used to derive
the feeding policy, searching for Fj continuous variables, and cD,in,j
discrete variables (j = 1,. . .,Ndiv ). Constraints g3 and g4 from Table 2
have not been included in the objective function, but are only used
for checking the severity of the operating conditions. As recom-
mended in literature, the number of time-arcs was considered
Ndiv = 8, larger values offering an improved solution flexibility, but
with higher computational and implementation costs. Other fixed
operating parameters concern the final batch time tf = 145 min,
the initial and feeding temperature To = Tin = 50 ◦ C, and initial
composition of Table 2. As MINLP solver, the adaptive random
search MMAMI of Maria (2003) has been used, together with the
random differential evolution algorithm of Storn (2008) with our
adaptation for MINLP problems.
SBR optimization has been performed in several alternatives,
and the derived feeding policies are compared to derive general
conclusions.
4.2.1. Feeding policies (a–c)
In a first approach, one determines the optimal feeding policy
Fj , j = 1,. . .,8, with considering only technological constraints g1 ,
G1 –G2 , without including the safety constraints g2 (Eq. (5)), and
keeping constant cD,in = 5.82 mol L−1 over the batch. Optimization
solution was derived under isothermal (a) or non-isothermal con-
ditions (b). The results, presented in Fig. 3, reveal the superiority
of non-isothermal approach, with a realized PAA yield of 0.5150
vs. 0.4664, being superior vs. all other feeding policies reported in
Fc , and ±2
 ). In a more prudent sub-optimal
literature for the same isothermal SBR and tf . The non-isothermal
operation solution has been derived also by keeping a constant low
cD,in = 3 mol L−1 level over the batch (solution (c) in Fig. 3). Even if
lower cD,in will lead to higher optimal F(t) levels, and vice-versa,
policies (b) and (c) are not fully equivalent, neither as temperature
profile (sharper for (c) case), nor as realized PAA yield (better for
(c) policy). Operation al lower cD,in clearly induces more flexibil-
ity in managing the feed flow-rates without escalating the process.
Isothermal operation, even if desirable for safety reasons, is how-
ever impossible to be implemented due to parameter variation
random character and very sensitive exothermic reactions.
4.2.2. Feeding policies (d1–d2)
In a second approach, one determines the optimal feeding policy
Fj , j = 1,. . .,8, with considering technological and safety constraints
g1 –g2 , G1 –G2 (Eq. (5)), and keeping cD,in = 5.82 mol L−1 constant over
the batch. In the alternative (d1), a small weight wg,2 = 0.1 has
been assigned to the safety requirements, the productivity goal
being prevalent. In the alternative (d2), the safety requirements
have been included in the SBR optimization with the same weight
wg,2 = 1.0 as for the productivity goal. The results, comparatively
presented in Fig. 4, reveal a continuous decline in the PAA yield as
the safety requirements are stronger in the optimization criteria.
This decline might be acceptable for a small weight of constraints
g2 , the realized yield of 0.5079 being close to the maximum of
0.5150. However, the probability of the risk that Fj (t) > Fc is in the
range of 1.3–9%, intersecting during one-time-arc the 95% confi-
dence region of the runaway boundaries (corresponding to random
fluctuations of ±2

Fig. 4. Optimal feed flow-rate policies F(t), with cD,in = 5.82 mol L−1 , compared to the critical values Fc (t) , temperature profile, and PAA yield dynamics, for the non-isothermal
SBR (STD(Fc ) =
Fc = standard deviation of Fc ). Optimal policies ensure Max nPAA ,f using Ndiv = 8 feed flow-rate arcs, and fixed tf = 145 min, under the technological constraints
g1 , G1 –G2 , and safety constraints g2 (Table 2). The imposed safety constraints are the followings: (b) non-isothermal operation with constant cD,in = 5.82 mol L−1 , under
constraints g1 , G1 –G2 (wg,2 = 0, g2 -neglected), realizing nPAA ,f = 0.4708 moles (net PAA yield 0.5150); (d1) non-isothermal operation with constant cD,in = 5.82 mol L−1 , under
constraints g1 , G1 –G2 , with safety constraints activated of weight wg,2 = 0.1, realizing nPAA ,f = 0.4657 moles (net PAA yield 0.5079); constraint g2 is violated with a time-
interval probability of g2 = [0.013, 0.018, 0.025, 0.032, 0.059, 0.020, 0.090, 0.033] (see Table 2 footnote); (d2) non-isothermal operation with constant cD,in = 5.82 mol L−1 , under
constraints g1 , G1 –G2 with safety constraint activated of weight wg,2 = 1, realizing nPAA ,f = 0.3587 mol (net PAA yield 0.3593); constraint g2 is violated with a time-interval
probability of g2 = [0.003, 0.005, 0.001, 0.009, 0.012, 0.019, 0.001, 0.008] (see Table 2 footnote).
 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189 187

Fig. 5. Optimal feed flow-rate policies F(t), with optimal cD,in = 3 mol L−1 (derived from cD,in ∈ [3,4,5,6] mol L−1 possibilities), compared to the critical values Fc (t), temperature
profile, and PAA yield dynamics, for the non-isothermal SBR (STD(Fc ) =
Fc = standard deviation of Fc ). Optimal policies ensure Max nPAA ,f using Ndiv = 8 feed flow-rate arcs,
and fixed tf = 145 min, under the technological constraints g1 , G1 –G2 , and safety constraints g2 (Table 2). The imposed safety constraints are the followings: (c) non-isothermal
operation with constant cD,in = 3 mol L−1 , under constraints g1 , G1 –G2 (wg,2 = 0, g2 -neglected), realizing nPAA ,f = 0.4820 moles (net PAA yield 0.5305); (e1) non-isothermal
operation with constant cD,in = 3 mol L−1 , under constraints g1 , G1 –G2 , with safety constraints activated of weight wg,2 = 0.1, realizing nPAA ,f = 0.4745 moles (net PAA yield
0.5201); constraint g2 is violated with a time-interval probability of g2 = [0.001, 0.007, 0.001, 0.016, 0.012, 0.014, 0.019, 0.007] (see Table 2 footnote); (e2) non-isothermal
operation with constant cD,in = 3 mol L−1 , under constraints g1 , G1 –G2 , with safety constraint activated of weight wg,2 = 1, realizing nPAA ,f = 0.4520 moles (net PAA yield 0.4889);
constraint g2 is violated with a time-interval probability of g2 = [0.001, 0.001, 0.002, 0.003, 0.006, 0.008, 0.010, 0.005] (see Table 2 footnote).

operation, the realized SBR productivity is lower (i.e. 0.3593 yield),
but the probability of violating the safety limits for Fj is very small,
i.e. in the range of 0.1–1.9%.
4.2.3. Feeding policies (e1–e2)
In a third approach, one determines the optimal feeding pol-
icy [Fj , cD,in,j ], j = 1,. . .,8, with including all technological and safety
constraints g1 –g2 , G1 –G2 (Eq. (5)). In the alternative (e1), a small
weight wg,2 = 0.1 is assigned to the safety constraints, in contrast
to a high weight wg,2 = 1 used in alternative (e2). The results, com-
paratively presented in Fig. 5, reveal two interesting conclusions.
Even if a continuous decrease in the PAA yield is obtained as more
importance is paid to the safety constraint (from 0.5305, to 0.5201,
and 0.4889 for policies c-e1–e2), running at low cD,in,j = 3 mol L−1 is
more advantageous, offering a higher yield comparatively to oper-
ation at a higher cD,in = 5.82 mol L−1 (policies b-d1–d2). The paid
price consists in manipulation of larger feeding flow-rates, and in an
insignificant increase of the thermal peak (with ca. 1 K). As another
conclusion, the probability of violating the safety limit confidence
region is much smaller at lower cD,in (in the range of 0.1–1%). Con-
sequently, operation at lower co-reactant D feeding concentrations
is more economic and safer. It should also be observed that, for this
case study, the operating severity declines for all policies towards
the end of the batch, due to requirements to limit the amount of
formed by-products.
In fact, a decision on choosing a suitable SBR feeding policy
that realizes a satisfactory productivity vs. safety compromise is
not easy to be taken, depending not only on raw-materials, prod-
ucts and other batch costs, but also on consequence costs when a
runaway happens with a certain frequency. More complicated sim-
ulations of accident consequence scenarios (AIChE, 2000; Maria,
2007), together with a detailed economic analysis of the batch in
connection to the market requirements might help in taking the
appropriate operating policy decision.
For instance, the optimal policy (d2) that severely met the safety
constraints for a cD,in = 5.82 mol L−1 level, leads to a decrease with
24% of the PAA productivity but consuming 47% less D reactant
than the policy (b) that ignores the safety constraints g2 [the con-
sumed
NdiD number of moles over the batch is given by the formula
v
(tf Fc
j=1 j D,in,j
)]. Similar conclusions can be derived for operation
at low cD,in = 3 mol L−1 level, the decline in the PAA productivity for
the operating policy (e2) being of 6% vs. the policy (c), but realizing
an economy of 16% of raw-material D (not mentioning that policies
e1–e2 fully fulfil the safety and flexibility requirements).
5. Conclusions
Optimal operating policy of a non-isothermal SBR can be sub-
stantially improved in terms of safety requirements if accurate
safety limits of the feasible parametric space can be determined.
Safety constraints can be included in the optimization objective
function in a probabilistic sense, by accounting for the parameter
uncertainty and penalizing risky rapprochements on the runaway
boundary confidence region in the parametric space.
The present work illustrates how the safety operating limits can
be model-based derived using a generalized sensitivity criterion
(MV), and how to be included during SBR optimization together
with the associated uncertainty. A concrete example is provided
188 G. Maria, A. Dan / Computers and Chemical Engineering 35 (2011) 177–189
for the SBR used for the acetoacetylation of pyrrole with diketene
in homogeneous liquid phase. While previous studies tried to maxi-
mize the isothermal reactor performances by model-based deriving
various optimal feeding policies of the co-reactant under semi-
empirically derived technological constraints, the present work
approaches the non-isothermal SBR with two manipulated input
variables (feeding solution concentration and flow-rate), by also
considering the safety requirements. Results suggest that a reason-
able compromise between reactor productivity vs. safety can be
realized, avoiding risky rapprochements of the running point on
the runaway boundary confidence band in the parametric planes.
The study also suggests that operation at low concentration levels
of the inlet solution is preferred, even if higher feed flow-rates have
to be manipulated. Thus, a considerable increase in both SBR pro-
ductivity and safety is obtained, without a considerable variation
of the thermal regime.
Even though it is computationally more intensive, the model-
based MV-method to derive the process safety limits is generally
applicable, offering less conservative predictions. Regular determi-
nation of the safety operating margins, exhibiting a high thermal
sensitivity, is necessary when changes in the systems’ geometry,
input conditions, raw-materials or catalyst’s characteristics occur.
The interest in accounting for precise safety limits during the SBR
optimization is justified by the economic implications of getting a
higher productivity by setting the nominal operating policy in the
vicinity of the safety limits.
The study also points-out that parameter random fluctuations
have to be considered not only in determining the new operation
set point of the reactor, but also when evaluating the confidence of
safety region according to the parameter distribution. This double
uncertainty in the operating parameters and critical conditions of
reactor operation has to be considered when determining the opti-
mal operating policy of the SBR in respect to a certain performance
criterion. The optimal operating solution has to be kept inside the
safety region, without intersecting the confidence region of the
runaway boundaries, instead preventing intersection of runaway
boundaries themselves. Such a solution corresponds to a minimum
probability of intersecting the safety limits for an assumed confi-
dence level and for an adopted weight of the safety constraint in
the objective function.
Since in many cases the most severe running conditions corre-
spond to a higher productivity, such a modified solution is expected
to offer a higher degree of safety in operation with the expense of a
certain decline in reactor productivity and of some supplementary
computational steps to derive the confidence of the safety limits.
Acknowledgement
This work was partially supported by CNCSIS-UEFISCSU, project
number PNII-IDEI 1543/2008–2011 “A nonlinear approach to con-
ceptual design and safe operation of chemical processes”.
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