Fundamental Principles

Scale-up & Reaction Runaway

Prof. Shishir Sinha
Department of Chemical Engineering

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 Introduction: What we will study
• Causes of over pressurization
• Heat of Reaction
• Adiabatic Temperature Rise
• Arrhenius relationship
• Thermal runaway
• Phi factor
• Heat loss (changes with scale)
• Reagent accumulation
• Onset temperature (exothermic events)
• Safety factors (for thermal hazards data)

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 Hazard arise from pressure
• When considering reaction hazards, temperature is rarely a hazard on
its own. The impact of any temperature rise on the system is much
more important.
• There are three potential sources of overpressure;
 Gas generation from the normal process
 Vapor pressure effects (as a consequence of
heat from the normal process)
 Heat from the normal process leading to
secondary reactions at elevated temperature
(gas/ vapor pressure effects)
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 Vapor Pressure Effects
• ANTOINE PLOT (The Antoine equation is a
class of semi-empirical correlations
describing the relation between vapor
pressure and temperature for pure
components. The Antoine equation is derived
from the Clausius–Clapeyronrelation). (can
be derived from sealed cell test data)
– loge(Pressure) = A + (B / (C + Temp))
• For a pure vapor pressure system:
𝑙𝑜𝑔𝑒 (𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒) ∝ 1/𝑇
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 Vapor Pressure Effects
𝐵
• Gas generating system: ln 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 = 𝐴 + 𝐶+𝑇𝑒𝑚𝑝𝑒𝑟𝑎𝑡𝑢𝑟𝑒
+𝜏
• Where 𝜏 is a factor due to the generation of permanent gas
• ln 𝑃𝑟𝑒𝑠𝑠𝑢𝑟𝑒 𝑖𝑠 𝑛𝑜𝑡 ∝ 1/𝑇

Vapor and Gas

ln (Pressure)

1/T

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 Heat of Reaction
• ΔHr (KJ/mol)
• For the reaction:-
𝐴 + 𝐵 → 𝑃𝑟𝑜𝑑𝑢𝑐𝑡𝑠
• The heat of reaction is the quantity of heat released or absorbed as
products are formed
• -ve Exothermic (heat released)
• +ve Endothermic (heat absorbed)

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 Heat of Reaction
• Acid/ Base Neutralization -60 kJ/mol
• Esterification
– Methanol/ Acetic Anhydride -67 kJ/mol
• Hydrolysis
– Diethylpropylmalonate -97 kJ/mol
• Diazotization
– Substituted amine hydrochloride -117 kJ/mol
• Methylation
– Complex acid chloride -104 kJ/mol
• Grignard Reaction -200 kJ/mol
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 Adiabatic Temperature Rise
• The total temperature rise in a reacting system due to exothermic
activity were there no heat loss to the surroundings.
∆𝑇𝑎𝑑 = ∆𝐻𝑟 . 𝑁/(𝑚. 𝐶𝑝 . 𝜙)
Where, N: No Moles of reactant (mol)
Cp: Heat capacity (J.kg-1.K-1)
ΔHr:Heat of reaction (J.mol-1)
m: Mass in reactor (kg)
Φ Phi factor (will be explained later later)

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 Reaction Rate
ARRHENIUS RELATIONSHIP: k = A.exp (-E/RT)
• Where; k: Rate constant
• A: Frequency factor
• E: Activation energy
• R: Rate of heat production is dependent on reaction rate (for pseudo
1st order reaction) by dQ/dt = k.ΔHr.m
• Where; dQ/dt = Rate of heat production
• k = Rate Constant (1st Order)
• m = Quantity of reagent available at time t
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 Reaction Kinetics
• Do not confuse ΔHr and EA (they have the same units)
─ ΔHr is the overall energy change during a process
 High ΔHr = a lot of energy change
 Low ΔHr = little energy change
• EA is the energy required to initiate the change
 Low EA = facile reaction (occur at lower
temperatures and / or pressures)
 High EA = difficult reaction (only occurs at higher
temperatures and /or pressures)
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 KINETICS OF HEAT RELEASE / LOSS
 HEAT RELEASE RATE
 from an exothermic reaction increases EXPONENTIALLY with
temperature
 HEAT LOSS RATE
 from a chemical reactor increases linearly with temperature
dQ/dt = U.A.ΔT
U = Heat transfer coefficient (W.m-2.K-1)
A = Heat transfer area (m2)
ΔT = Temperature difference b/w contents and jacket
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 Thermal Runaway
Heat generation due
to exothermic dQ/dT>
process U.A.ΔT
Heat Removal due
to cooling
dQ/dT (W)

Temperature (K) Critical Temperature

Reaction out of control → Thermal Runaway
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 Thermal Runaway
• A THERMAL RUNAWAY is the progressive Heat generation due
to exothermic
process
dQ/d
T>
U.A.

production of heat from a chemical process and

ΔT
Heat Removal due
to cooling

dQ/dT (W)
occurs when the rate of heat production
exceeds the rate of heat removal. Temperature
(K)
Critical Temperature

Reaction out of control → Thermal Runaway

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 Causes of Thermal Runaway
Studies have determined that thermal runaway reactions occur due to the
following four reasons:
• Insufficient understanding of the process chemistry and the
energy/kinetics for the desired reactions,
• Improper design of the heat transfer capacity required at the plant
level,
• Insufficient understanding of the adverse reaction
and controls including plant-safety back-up
systems, as well as adequate emergency venting,
• Inadequate written batch procedures and poor
operator training.
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 Causes of Thermal Runaway
• Never assume a chemical is not hazardous because of a low-hazard
rating. Many incidents involve materials that have National Fire
Protection Association (NFPA) hazard ratings of 0 and 1.
• It is best to develop a proper testing program to identify and
characterize all reactive materials and reaction mixtures under a
variety of process conditions.

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 Causes of Thermal Runaway
• Subsequently a process hazard analysis can then be used to assign
appropriate controls and safeguards to reduce risk of an adverse event.
• It is important to remember to update the process safety information,
as a process undergoes changes during its lifecycle.
• The interim process-safety information reports
can then serve as a reference for technology-
transfer purposes as the process scales from
R&D, kilo-lab, pilot plant to commercial-
production stage.

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 Causes of Thermal Runaway
• Once the process has been set, the final process safety report can then
be used by a variety of end users either in-house or by outsource
facilities.
• When developing safety documentation, it is important to keep in
mind that it must comply with company policies and procedures as
well as country and local regulations.

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 Kinetic Complications….
• Beware assuming simple kinetics for :
– autocatalytic reactions
– heterogeneous reactions
 mass transfer may be rate determining
 phase transfer agents may dictate rate
 complex reactions (multiple steps / routes)

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 PHI FACTOR
A correction factor which is based on the ratio of the total heat capacity
of a vessel and the total heat capacity of the vessel contents . The phi-
factor approaches the value of one for large vessels, for extremely light
vessels, or at genuine adiabatic conditions. The PHI-factor (Φ) is
equivalent to the thermal inertia.
𝐴 + 𝐵 → 𝑃𝑟𝑜𝑑𝑢𝑐𝑡
(𝑀𝑎𝑠𝑠 𝑜𝑓 𝑐𝑜𝑛𝑡𝑎𝑖𝑛𝑒𝑟 𝑋 𝐻𝑒𝑎𝑡 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 𝑜𝑓 𝑐𝑜𝑛𝑡𝑎𝑖𝑛𝑒𝑟)
• 𝜙 =1+ (𝑀𝑎𝑠𝑠 𝑜𝑓 𝑆𝑎𝑚𝑝𝑙𝑒 𝑋 𝐻𝑒𝑎𝑡 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒)

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 PHI FACTOR
• The heat generated in an exothermic reaction is consumed
in three ways
– To raise the temperature of REACTION MASS
– To raise the temperature of the REACTOR
– Heat loss to the ENVIRONMENT

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 PHI FACTOR
If PHI > 1 then it is considered in thermodynamic and
kinetic calculations
1 m³ Glass lined reactor (Jacket empty) 1.41
10 m³ Glass lined reactor (Jacket empty) 1.13
10g Carious tube screening test (best) 2.50
Accelerating Rate Calorimeter (best) 1.50
Adiabatic Pressure Dewar Calorimeter 1.05
(best)

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 Testing
Testing should:
• Consider the consequences of all conceivable process deviations.
• Be conducted under plant scale heat loss conditions (or have an
appropriate safety factor applied).
• Replicate plant conditions in all ways possible (including use of plant
materials, consideration of materials of plant construction, etc).

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 Reaction Accumulation
A condition when; Rate of reactant addition > Rate of reaction

Work off
period

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 Reaction Accumulation
Determined by process analysis
Causes (Not exhaustive) :
• Wrong kinetic assumptions
• Inefficient agitation
• Poor temperature control
• Impurities
• Incorrect initiation

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 Onset Temperature: Concept
• The onset temperature is the temperature at which a reaction
can be detected under the prevailing heat loss and PHI factor
conditions of the test.
• For a given reaction, it is equipment dependent and not a
constant!
• Normally quoted as the temperature at which
the rate of self-heating exceeds a threshold
value.

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 Safety Factors
• Safety factors are applied to data collected in high phi factor or
high heat loss test equipment.
 50 - 100 K for screening tests.
 10 - 50 K for adiabatic tests.
• Always apply a conservative factor to account for kinetic
deviations between reaction types.
• Beware of autocatalytic reactions or processes
with an induction or inhibition period.
• Consider air availability when assessing results
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 Safety Factors
• Safety factor is a margin of safety against risk. Conventionally for
screening and adiabatic test, a margin of 50 to 100K and 10 to
50K is taken in calculation, respectively. As adiabatic testing is
majorly done during scale-up and pilot plant preparation. Hence,
low margin of temperature is usually required.

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 Safety Considerations
Preliminary hazard assessment:
• Determine the thermal stability of all reaction components/mixtures
within the minimum and maximum process temperatures attainable
under a worst-case scenario,
• Identify unwanted interaction between reagents and solvents, and
• Identify potential reaction contaminants that may have an inhibitory or
catalytic effect on the desired reaction.

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 Safety Considerations
Quantification of desired reactions:
• Determine the heat of reaction and off-gas rates for the desired and
quench reactions, including the heat resulting from accumulation of
reagents or slow forming intermediates,
• Determine the maximum adiabatic temperature for the reaction, and
determine the basis of safety relative to the estimated boiling point of
the reaction mixture, and
• Understand the relative rates of all chemical
reactions.

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 Safety Considerations
Quantification of adverse reactions:
• Assess the thermal stability of the reaction mixture over a wide
temperature range
• When optimizing the robustness of the process, consider other
reaction variables, such as pH, concentration, conversion rate, off-gas
rate, stability of starting and product substrates in solution and as a
slurry

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 Safety Considerations
Quantification of adverse reactions:
• Consider the potential and impact of unwanted vapor-phase reactions,
and
• Develop a chemical-interaction matrix for materials present in the
reaction mixture, classify the reactivity, and communicate this
information to operational personnel

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 Safety Considerations
Plant considerations:
• Conduct a basic energy balance to consider the heats during various
additions, heat generated during the chemical reaction, and the heat
removal capability of the plant reactor system. Remember to include
reactor agitation as a source of energy,
• Consider the impact of possible deviations from the intended reactant
charges and operating conditions,

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 Safety Considerations
Plant considerations:
• Identify all heat sources connected to a reaction vessel and assume the
maximum possible worst-case scenario,
• Determine the effect of the lowest possible temperature to which the
reactor heat-transfer fluid could cool the reaction mixture, i.e., coating
heat transfer surface, and
• Consider the impact of temperature gradients and
other issues, such as increased viscosity, freezing at
reactor walls, fouling, and so on, in plant-scale
equipment.
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 References
• https://www.aiche.org/ccps/resources/glossary/process-safety-glossary/phi-factor
• https://infoscience.epfl.ch/record/229409?ln=en
• Fauske & Associates, blog, How to Scale-up Chemical Reactions/ Runaway Reactions in
a Safer Way, link: https://www.fauske.com/blog/bid/401398/how-to-scale-up-
chemical-reactions-runaway-reactions-in-a-safer-way
• Safety Issues In The Scale-up Of Chemical Reactions, RSC Publication, URL:
http://www.rsc.org/globalassets/04-campaigning-outreach/realising-potential-of-
scientists/regulations-health-safety/safety-issues-in-the-scaleup-of-chemical-
reactions.pdf

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Thank You

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