Expose Crist Eng

Crystallization
—
Thermodynamics of crystallization
Baptiste Bouillot
Mines Saint-Etienne - SPIN Centre
2021-2022
Solubility
Thermodynamic experiments and modelling
A few words about crystals
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Baptiste Bouillot Crystalization Thermodynamics
Solubility
crystal
Solid that comprises a rigid lattice of molecules, atoms or ions, the location of
which are characteristic of the substance. This lattice presents a specific
organization and some degree of symmetry.
Examples :
Figure – The three cubic lattice : (a) cube ; (b) body-centred cube ; (c) face centred
cube (Mullin, 2001)
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Solubility
More generally :
Figure – The seven crystal systems (Mullin, 2001)
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Solubility
A few words about crystallization
In simple words :
nucleation
growth
agglomeration
©Mettler-Toledo
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Solubility
In simple words :
nucleation(today and later)
growth (to be discussed later)
agglomeration (to be discussed later)
©Mettler-Toledo
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Solubility
CRYSTALLIZATION or/vs PRECIPITATION ? ? ?
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Solubility
What is it for ?
Generation of solids
Why ?
Separation process
Purification of compounds
Generation of specific solids (metals...)
where is it considered/employed ?
chemistry, fine chemicals
pharmaceuticals (more than 80% of active pharmaceutical ingredients)
food industry (powdered milk, sugar, salt...)
metalworking & Hydrometallurgy
petroleum industry (crystallization in pipes and purification)
recycling (Hydrometallurgy, water treatment)
mining
natural processes
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Solubility
Challenges in Crystallization
Some challenges :
nucleation and seeding
crystal growth (control of crystalline properties)
oiling out (phase separation)
fragmentation
polymorphism
co-crystalization
deracemization
These considerations play a key role in the result of a crystallization process.
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Solubility
Challenges in Crystallization : definitions/terms
Co-crystal
Solid composed of several different compounds in an unique crystalline
structure. That includes also :
solvates
hydrates (solvates with water as solvent)
clathrates
Polymorphism
Polymorphism defines the existence of a solid material in two or more crystal
structures, known as polymorphs.
example : paracetamol (monoclinic and orthohombic structures)
Deracemization
Deracemization is defined as the conversion of a racemate into a pure (or
excess) enantiomer.
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Solubility
Organization of UP “Crystallization”
1
Thermodynamics of crystallization (today)
2
Kinetics of crystallization (Ana Cameirao)
nucleation
crystal growth
crystallizer design
agglomeration
3
Population balance (Ana Cameirao)
4
Multi-phase transfers (Gianluca Lavalle)
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Solubility
Outline
1 Thermodynamics of crystallization
2 Solubility
3 Thermodynamic experiments and modelling
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Thermodynamics of crystallization Fundamental understanding
Solubility Phase Diagrams
Thermodynamic experiments and modelling Pure component
Outline
2 Solubility
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Nucleation
Nucleation
Nucleation is simply defined as the first random formation of a distinct
thermodynamic new phase (daughter phase or nucleus (an ensemble of
atoms)) that have the ability to irreversibly grow into larger sized nucleus
within the body of a metastable parent phase.
Nucleation requires activation energy, corresponding to an energy barrier to

overcome (see next slides).
Thermodynamic condition for nucleation ? ? ? Let’s consider an open system

at T end P, the most standard condition.
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Nucleation : Thermodynamic condition
atmosphere atmosphere at new T and P

at T and P
after a
T while...
nucleus
metastable phase
When does that happen ?
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Nucleation : Thermodynamic condition
at T and P, equilibrium ↔ Gibbs energy minimization (GT,P )
Gliq(T,P,x)
Gliq(T,P,x)
Gsolid
liquid
int Gliq
erf
ac
e Ginter
G total ?
solid
Gsolid
Gsyst = Gliq. + Gsolid + Ginterface
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Nucleation
Gliq(T,P,x)
Ginter
Gliq(T,P,x) ?
Gsolid
Driving force and nucleation condition 1 :
∆G = [Gliq. + Gsolid + Ginter ] − Gpure

liq.
∆G > 0 ⇒ only liquid or solid metastable

∆G < 0 ⇒ only solid, or liquid metastable awaiting for crystallization
∆G = 0 ⇒ liquid - solid equilibrium (nothing happens)
How can ∆G be expressed ?
1. N.B. : See also TD4 (dropplet nucleation), 1st year thermodynamic lessons
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Nucleation : Gibbs approach (1)
Let us consider the Gibbs free energy of such system. Remember that :
P
G(T, P, x) = i Ni µi
P
dG = −SdT + Vdp + i Ni dµi
In the interface :
there is no molecules at all and therefore, no volume, hence :
ntotal
i = nliq solid
i + ni (no molecules inside interface)
V total = V liq + V solid
BUT the interface has free energy ! ! !
The interface free energy takes the form :
Ginter = γΣ
with γ the interfacial tension (surface energy), and Σ the interface surface.
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Let us go back to ∆G :
∆G(T, P, x) = Gliq + Gsolid + GΣ − Gpure

liq
This energy can be described by two terms 2 :

a surface term GS or ∆GS
a volume term GV or ∆GV
Therefore :
∆G = ∆GS + ∆GV
or, using volumic quantities :
∆G = 4πr2 γ + 43 πr3 ∆Gv
where ∆Gv is the volumic Gibbs energy, r the radius of the nucleus
(assuming a sphere).
2. Note that it is also possible to express ∆G by derivating the chemical potentials (see later).
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How do these quantities behave ?

∆GS > 0 → creating an interface “costs energy”
∆GV < 0 → forming a new phase decreases energy (natural
transformation)
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transformation)
Free energy
γ
0
0 nucleus size
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transformation)
∆GS increases with r2

∆GV decreases with r3
Free energy
γ
0 4
∆Gcrit = πγrc2
3
−2γ
rc =
∆Gv
0 nucleus size
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Phase diagrams : case of water

Let’s have a look at water phase diagram
Figure – Simple water phase diagram (wikipedia)
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Phase diagrams : case of water

Let’s have a look at water phase diagram
Figure – Water phase diagram (Martin Chaplin)
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Phase diagrams : general case

General case of two compounds
Figure – Phase diagram showing eutectic (Mullin, 2001)

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Figure – Phase diagram for the simple eutectic system naphtalene-benzene (Mullin,
2001)
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Figure – Water-NaCl phase diagram (Mullin, 2001)
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Gibbs Phase Rule
How many degree of freedom ? :
F =N−Φ+2−R (1)
avec :
F degree of freedom,
N number of components (molecules),
Φ number of phases,
R constraints (additional relations such as, constant composition,
chemical reaction, azeotropy...).
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Gibbs Phase Rule

How many degree of freedom ? :
F =N−Φ+2−R (1)
avec :
F degree of freedom,
N number of components (molecules),
Φ number of phases,
R constraints (additional relations such as, constant composition,
chemical reaction, azeotropy...).
P (bar) critical point
220
fusion
)
(T
P (s)
line
Example :
Liquid
- Single component system/single phase : Solid
F=2 1 vaporization
- Single component / two phases : F = 1 triple point curve
- Singel component / three phases : F = 0 0.006 sublimation

curve
Gas
273,15
273.16 373.15 673.16 T (K)

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Thermodynamic properties of pure compounds
There are several important thermodynamics properties :

the metling point (or point of fusion) :
melting (fusion) temperature : Tf
melting (fusion) enthalpy : ∆Hf (J) or ∆Hf m (J/mol) or ∆hf (J/kg)
melting entropy : ∆Sf (J/K) or ∆Sf m (J/mol/K) or ∆sf (J/kg)
the heat capacities :
liquid : Cpliq (J/K) or cliq
p (J/K/kg)
solid : Cpsol csol
p (J/K/kg)
How do we obtain them ? with DSC (Differential Scanning Calorimetry)
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DSC : Differential Scanning Calorimetry
Figure – DSC apparatus and inside (Wikipedia)
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échantillon référence
résistances résistances
chauffantes thermomètres
Figure – Power-compensation DSC
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échantillon référence
T(t)
1
3 ΔT << PC
Enregistreur
Calibration K(T)
Figure – Heat-flux DSC
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Sample: paracetamol_pur1 File: paracetamol 1°C par min de 130 à 220 ...
Size: 1.9200 mg DSC Operator: BB
Method: Ramp Run Date: 30Mar2011 10:41
Instrument: DSC Q2000 V24.4 Build 116
168.69°C
181.4J/g
0
Heat Flow (W/g)
2
4
169.05°C
6
164 166 168 170 172 174 176 178
Exo Up Temperature (°C) Universal V4.7A TA Instruments
Figure – DSC curve for paracetamol

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Clapeyron equation : presentation
P (bar)
Equilibrium lines (including fusion) can be
Fusion
line
described by Clapeyron equation :
Solid Liquid dp ∆H
=
dT T∆V
vaporization
curve
with :
sublimation
curve
triple point
Gas ∆H the enthalpy change (latent heat)
T (K) ∆V the volume change
This equation provides the relation between the fusion curve p(T) and the
latent heat.
for fusion :
dp ∆Hf
dT
= T(Vliq. −Vsolid )
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Thermodynamics of crystallization Solubility :Case of mixtures
Solubility Solid-Liquid Equilibrium (SLE)
Thermodynamic experiments and modelling Supersaturation & supersaturation ratio
Outline
2 Solubility
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Solubility
Definition : Solubility
Solid-liquid equilibrium of a solute in a solvent :
Concentration solubility
curve
supersaturation
zone
undersaturation
zone
Temperature
Solubility is the mole fraction at equilibrium 3
Remember Gibbs phase law : 2 degrees of freedom
Note that p does not influence SLE significantly.
3. sometimes provided in mole or mass concentration

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Solubility and crystallization
solubility
spontaneous
metastable
crystallization
zone
A
Concentration
Temperature
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solubility solven
t pow
er
more powerful
Temperature
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How to crystallize ?
Temperature decrease
Solvent evaporation
Anti-solvent addition
Chemical reaction inducing high supersaturation
Anyway, solubility is always needed !
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How to crystallize ?
Temperature decrease
Solvent evaporation
Anti-solvent addition
Chemical reaction inducing high supersaturation
Anyway, solubility is always needed !
How to determine solubility ?

experimentally
correlations
thermodynamic models
We will get back to that in the end...
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Solid-Liquid Equilibrium (SLE)
How to obtain SLE equation ?
At equilibrium, T, p and µi are the same in each phase (i molecule),

therefore :
∀i , µliq.
i = µsolid
i (2)
Usually, for liquid part :
µliq.
i = µref
i + RT ln (xi γi ) (3)
or :
µliq.
i = µpure
i
liq.
+ RT ln (xi γi ) (4)
What about µsolid.
i ?
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Solid-Liquid Equilibrium (SLE)
How to obtain SLE equation ?
At equilibrium, T, p and µi are the same in each phase (i molecule),

therefore :
∀i , µliq.
i = µsolid
i (2)
Usually, for liquid part :
µliq.
i = µref
i + RT ln (xi γi ) (5)
or :
µliq.
i = µpure
i
liq.
What about µsolid
i ?
. solid
µsolid
i = µref
i (7)
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Exercise : LSE equation

Find the final SLE equation
to help you : Use the Gibbs-Helmoltz equation ( ∂G/T = − TH2 )
∂T
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Exercise : LSE equation

Find the final SLE equation
Thermodynamic equilibrium :
µsolide
i = µliquide
i (8)
let’s take as a reference state : pure liquid at T and P
µsolide
i = µpure
i
liquid
therefore :
µsolid
i − µpure
i
liquid
Gm solide
i − Gm pure
i
liquid
∆Gm SL
i
ln (xi γi ) = = = (10)
RT RT RT
+ Gibbs-Helmoltz :
∂G/T H
=− 2 (11)
∂T T
from where (assuming H independent T) :
∆Hm fus

Tfus
ln x2 γ2 = 1− (12)
RTfus T
with 2 the solute index, and more rigorously :
∆Hm fus Tfus

∆CP m
Tfus Tfus

ln x2 γ2 = RTfus
1− T
− R
ln T
− T
+1 (13)
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Ideal solubility
Ideal solubility corresponds to Ideal solution :
γi = 1
Therefore, equation ?? becomes :

∆Hm fus Tfus ∆CPm Tfus Tfus
ln x = 1− − ln − +1 (14)
RTfus T R T T
Ideal solubility x only depends on thermodynamic properties of the crystal.
Example :
Figure – Ideal solubility of ibuprofene compared to solubility in solvents 30/57

Solvent power
0
0,0031 0,0032 0,0033 0,0034 0,0035 0,0036
-0,5
γ<1
-1
-1,5
ln(x)
Cas idéal
Octanol
-2
Cyclohexane
Acétate d'éthyle
Chloroforme
-2,5 Ethanol
Acétone
Heptane
-3
Isopropanol γ>1
Toluène
THF
DMSO
-3,5
1/T
Figure – Ideal solubility of ibuprofene compared to solubility in solvents
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Solvent power
Solvent power
“power” of solvent tells how much the solubility is
Two influences :
the temperature (the higher the more soluble)
the solvent molecule
Can be somehow given by the activity coefficient γ.
Mostly depends on molecular interactions when it come to the solvent

choice.
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Solubility product
Solubility product
Kc : Provide solubility of soluble electrolytes in water.
When a molecules dissociates in solution, such as :
Mx Ay xM z+ + yAz− (15)
with z+ and z− are valencies of the ions.
Then for satuarted solution :
Kc = (c+)x + (c−)y = constant (16)
where (c+)x and (c−)y are ionic concentrations expressed as mol/L.
These constants are usually recorded as pK values (pKc = −log(Kc )) so that

Kc = 10−5 → pKc = 5 4 .
4. log provides a better scale to compare concentration since log(10.c) = log(c) + 1 = pKc + 1
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Polymorphism and racemates
Polymorph = same molecule, but 6= structure
⇒ Different thermodynamic properties. Example of paracetamol :

Form I (monoclinic) : Tf = 442.1 K, ∆Hm f = 27470.6 J/mol
Form II (orthorhombic) : Tf = 429.7 K, ∆Hm f = 26500 J/mol
Figure – Ideal solubility of paracetamol (form I & II)

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Polymorphism and racemates
Polymorph = same molecule, but 6= structure
⇒ Different thermodynamic properties. Example of paracetamol :

Form I (monoclinic) : Tf = 442.1 K, ∆Hm f = 27470.6 J/mol
Form II (orthorhombic) : Tf = 429.7 K, ∆Hm f = 26500 J/mol
Figure – Paracetamol solubility into water for two forms (Agnew et al. 2016, in Chem.
Commun. 52)
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Polymorphism : Ostwald’s rule of stages
Ostwald’s rule of stages

“an unstable system does not necessarilly transform directly into the most
stable state, but into the one that most closely resemble its own” (smallest
loss of energy, usually metastable)
solubility solubility
form I form II form I form II
cooling cooling
kinetic crystallization
of metastable form I kinetic crystallization
of stable form II
Temperature Temperature
Figure – Solubility and crystallization of polymorphs
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Polymorphism management/isolation
Management solutions :
lower supersaturation (no metastable formation)
seeding (see below)
heating recrystallization
solubility solubility
form I form II form I form II
cooling cooling
kinetic crystallization
of metastable form I kinetic crystallization
of stable form II
Temperature Temperature
Figure – Solubility and crystallization of polymorphs
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Polymorphism management/isolation
Management solutions :
lower supersaturation (no metastable formation)
seeding (see below)
heating recrystallization
solubility
form I form II
seeding form II
cooling
form II nucleation
and growth
Temperature
Figure – Polymorph management with seeding
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Racetmates management
Crystalline racemates can be :
conglomerate : equimolal physical mixture of two enantiomorphs
racemic : two enantiomers homogeneously distributed in crystal lattice
Crystallization is a good way to sort enantiomers thanks to eutectic point :
Figure – Phase diagrams : (a) for conglomerates, (b) racemic compounds (Mullin,
2001)
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Supersaturation & supersaturation ratio

What is the driving force for crystallization ?
→ ∆µ, the chemical potential gradient. Let’s have a look :
∆µi = µliq liqequilibrium

i − µi (17)
0
Assuming the same reference point µ , the pure solute at T and p :
h i h i
∆µi = µ0i + RT ln(ai ) − µ0i − RT ln(aeq.
i ) (18)
Therefore :
ai
∆µi = RT ln (19)
a0i
or
∆µi
= ln (S) (20)
RT
S is the fundamental supersaturation :
S = a/aeq = exp (∆µ/RT)

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Then, commonly :
Supersaturation ratio
talking in activities is not common/easy, then
Sc = ci /ceq eq eq
i ; Sm = mi /mi ; Sx = xi /xi
with ci the molar concentration, mi molality (mol/kg solvent), and xi molar

fraction.
Concentration driving force
∆c = ci − ceq
i
Relative supersaturation
σ= ∆
ceq
c
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In terms of measurable quantities ?

xi γi
S = a/aeq = (21)
xieq γieq
then :
γi
S = Sx + (22)
γieq
For ideal solutions, S = Sx .

Otherwise activity coefficients are needed !
Finally, note that there is a final term, related to supersaturation :
Supercooling
∆T = T eq − T
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Experimental methods
Correlations
Solubility
Modelling
Example of models for solubility
Outline
2 Solubility
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Correlations
Solubility
Modelling
Experimental solubility
3 standard methods :
polythermal method
gravimetric, or isothermal, method
analytic method
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Correlations
Solubility
Modelling
Polythermal method
Base on temperature back and forth in a crystallization/dissolution cycle :

sonde / turbidimeter
T (°C) complete
turbidity/absorbance
dissolution
nucleation
Tsat
mixture
solvent/solute 0
of known time, s
composition
Figure – Polythermal method for solubility measurment
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Correlations
Solubility
Modelling
Polythermal method
Base on temperature back and forth in a crystallization/dissolution cycle :
Figure – Refractive index (a) and concentration (b) changes during solubility
measurment by polythermal method (After Nyvlt, 1997, reproduced in Mullin, 2001)
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Correlations
Solubility
Modelling
Isothermal method
The point is to dillute solute into solvent until some particles remains at
controlled temperature.
controlled mass msolid
added to solution
initial mass msolv

of solvent
T
stirring system
Figure – Isothermal method for solubility measurment
When the solute does not dissolve anymore, the solution is saturated.
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Correlations
Solubility
Modelling
Analytic method
Supersaturated
solution
analysis of
waiting for
equilibrium liquid mixture at the
equilibrium supernatant:
(24h), then
- IR
rest
- UV-Visible
- RAMAN
solid phase gravimetric analysis
Figure – Analystic method for solubility measurment
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Correlations
Solubility
Modelling
Solubility correlations
From solubility data, simple correlation can be acheived.
Commonly, it looks like c = A + Bt + Ct2 + ..., using concentration, with t in

° C. Otherwise, here are some example of expressions :

 log x = A + BT
2

 log x = A + BT + CT


−1
log x = A + BT (23)
log x = A + BT −1 + CT −2




log x = A + BT −1 + C log T

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Correlations
Solubility
Modelling
Solubility correlations : example of ascorbic acid

Ascorbic acid (aspirin) with :
log x = A + BT + CT 2 (24)
Figure – Ascorbic acid solubility in water (blue circle) with correlation 24
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Correlations
Solubility
Modelling
Reminder SLE equation
Two equations for solubility. The rigorous one :
∆Hm fus ∆CPm

Tfus Tfus Tfus
ln x2 γ2 = RTfus
1− T
− R
ln T
− T
+1
The simplified one :

∆Hm fus

Tfus
ln x2 γ2 = RTfus
1− T
γ, the activity coefficient, needs to be modeled.
This is the purpose of “advanced thermodynamic” lesson in “Process for

Energy” class ! ! !
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Correlations
Solubility
Modelling
Molecular interactions
Molecular interactions (attractive and repulsive forces).
δ+
δ+
δ- (1)
four different attractive δ-
interactions :
dispersion forces (or London δ+ δ- δ+ (2)
δ-
forces),
Debye forces, δ+ δ- (3)
δ+
Keesom forces, δ-
chemical forces (such as
(4)
hydrogen bonds). O H O H
H H
+ repulsive short distance → hard sphere
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Correlations
Solubility
Modelling
Ideal model
Ideal model
no deviation from ideal gas (→ perfect gas), or ideal solution :
γiα = 1

(25)
φαi = 1
0
0,0031 0,0032 0,0033 0,0034 0,0035 0,0036
-0,5
γ<1
-1
-1,5
ln(x)
Cas idéal
Octanol
-2
Cyclohexane
Acétate d'éthyle
Chloroforme
-2,5 Ethanol
Acétone
Heptane
-3
Isopropanol γ>1
Toluène
THF
DMSO
-3,5
1/T
Figure – Ideal solubility of ibuprofene compared to solubility in solvents

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Correlations
Solubility
Modelling
Some models that can be used for solubility prediction

Activity coefficient models that can be semi-empirical, or predictive :
semi-empirical :
solubility parameters (regular solutions)
NRTL
UNIQUAC
NRTL-SAC
COSMO-SAC
Predictive :
UNIFAC
COSMO-RS
And equations of state :
PC-SAFT
PPC-SAFT
...
These last have prooved to be very promissing for more complexe systems.
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Correlations
Solubility
Modelling
Simple case of solubility parameters
Sometimes called Hansen solubility parameters, this method rely on regular

solution approach.
Regular solutions for binary system
RT ln γ1 = v1 Φ21 (δ1 − δ2 ) (26)
Solubility parameters δi are used for molecules, and is Φi is the volume

fraction of i.
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Examples - Exercices
Example : Freezing/melting point of water

How to predict melting point of water ?
Which equation ? ? ?
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 ln xw γw = ∆Hm fus 1 − Tfus


RTfus T
 ln xw γw = ∆Hm fus 1 − Tfus − ∆CPm ln

Tfus Tfus
RTfus T R T
− T
+1
Do we know ∆Hm fus , Tfus , ∆CPm , or how to know ?
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∆Hm fus Tfus
ln xw γw = 1−
RTfus T
with ∆Hm fus = 6008 J/mol, Tfus 273.15 K =, and ∆CPm = 38.7 J/mol/K (note
that ∆Cp m is usually not known, hence neglected).
What about γw ? ? ?
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 ln xw γw = ∆Hm fus 1 − Tfus


RTfus T
 ln xw γw = ∆Hm fus 1 − Tfus − ∆CPm ln

Tfus Tfus
RTfus T R T
− T
+1
Do we know ∆Hm fus , Tfus , ∆CPm ?, or how to know ?
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ln xw γw = 1− − ln − +1
RTfus T R T T
Thanks to DSC, ∆Hm fus = 6008 J/mol, Tfus 273.15 K =, and ∆CPm =
38.7 J/mol/K (note that ∆Cp m is usually not known, hence neglected).
only water → γw = 1
Water + additives ? ? ? (for instance, ethanol) → need γ model
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ln xw γw = 1− − ln − +1
RTfus T R T T
Let’s consider two suffixes Margules (see advanced thermodynamics) :

2
ln γw = xEtOH [A + 2(B − A)xw ]
What about A and B ?
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ln xw γw = 1− − ln − +1
RTfus T R T T
Let’s consider two suffixes Margules (see advanced thermodynamics) :

2
ln γw = xEtOH [A + 2(B − A)xw ]

A = 0.6923
B = 1.6432
solver → Tf (10%molEtOH ) = 264.78 K
with xEtOH = 10% ↔ yEtOH = 22.13%
not perfect... but close !
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More complex model of NRTL-SAC : introduction to “exercise”
NRTL-SAC
NRTL-SAC (NonRandom Two-Liquids Segment Activity Coefficient) model is
a NRTL-based approach adapted to liquid/solid equilibria
Division of molecules into conceptual segments
Hydrophobic (X)
Polar attractive (Y + ) and repulsive (Y − )
Hydrophilic (Z)
→ four parameters (X Y + Y − Z)
Polaire attracteur
Hydrophobe Hydrophile
Polaire répulsif
ln γi = ln γicombinatorial + ln γiresidual (composition, T, [XY − Y + Z]) (27)
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Exercice : LSE with NRTL-SAC

An R&D Process Engineer at Sanofi-Aventis is looking for a good crystallization
solvent for ibuprofen
He already has some data on the solubility of his molecules in textitsome solvents.
Help him use the thermodynamic model NRTL-SAC for textitpredict solubility
(orders of magnitude) in other solvents to save time (and money !).
For that :
Develop a algorithm of calculation solubility (SL balance).
Use the data already acquired for determine the parameters of the AB10C20
molecule.
Apply the method, and predict solubility in isopropanol.
Solvent parameters and model code (CAMPUS) are given :
Solvent X Y- Y+ Z solubility Temperature (K)
acetone 0.131 0.109 0.513 0. 0.19992 293.15

ethanol 0.256 0.081 0. 0.507 0.1671 293.15
chloroforme 0.278 0. 0.039 0. 0.2718 293.15
cyclohexane 0.892 0. 0. 0. 0.1122 298.15
octanol 0.766 0.032 0.624 0.335 0.343 298.15
ethyl acetate 0.322 0.049 0.421 0. 0.1850 293.15
55/57
Exercice : solution
choose T
guess
solubility x
calculate
activity coefficicent
? no
yes
solubility x
correct !
56/57
Exercice : solution
choose
experimental data
Guess model
parameters
guess
solubility x
calculate
activity coefficicent
? no
yes
no
x predicted = x exp ?
yes
parameters OK
56/57
The End
. Most of this lesson has been inspired by the “famous” Mullin book : J.W Mullin, Crystallization,
fourth edition, Butterworth-Heinmann, 2001
57/57

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Crystallization

Mines Saint-Etienne - SPIN Centre

A few words about crystals

A few words about crystals

A few words about crystals

Figure – The seven crystal systems (Mullin, 2001)

A few words about crystallization

A few words about crystallization

A few words about crystallization

CRYSTALLIZATION or/vs PRECIPITATION ? ? ?

Challenges in Crystallization : definitions/terms

3 Thermodynamic experiments and modelling

3 Thermodynamic experiments and modelling

Nucleation requires activation energy, corresponding to an energy barrier to

Thermodynamic condition for nucleation ? ? ? Let’s consider an open system

Nucleation : Thermodynamic condition

atmosphere atmosphere at new T and P

When does that happen ?

Nucleation : Thermodynamic condition

at T and P, equilibrium ↔ Gibbs energy minimization (GT,P )

Gsyst = Gliq. + Gsolid + Ginterface

Driving force and nucleation condition 1 :

∆G = [Gliq. + Gsolid + Ginter ] − Gpure

∆G > 0 ⇒ only liquid or solid metastable

Nucleation : Gibbs approach (1)

Nucleation : Gibbs approach (2)

∆G(T, P, x) = Gliq + Gsolid + GΣ − Gpure

This energy can be described by two terms 2 :

∆G = 4πr2 γ + 43 πr3 ∆Gv

Nucleation : Gibbs approach (3)

How do these quantities behave ?

Nucleation : Gibbs approach (3)

How do these quantities behave ?

Nucleation : Gibbs approach (3)

How do these quantities behave ?

∆GS increases with r2

Phase diagrams : case of water

Figure – Simple water phase diagram (wikipedia)

Phase diagrams : case of water

Figure – Water phase diagram (Martin Chaplin)

Phase diagrams : general case

Figure – Phase diagram showing eutectic (Mullin, 2001)

Phase diagrams : general case

Phase diagrams : general case

Figure – Water-NaCl phase diagram (Mullin, 2001)

Gibbs Phase Rule

How many degree of freedom ? :

Gibbs Phase Rule

- Singel component / three phases : F = 0 0.006 sublimation

273.16 373.15 673.16 T (K)

Thermodynamic properties of pure compounds

There are several important thermodynamics properties :

How do we obtain them ? with DSC (Differential Scanning Calorimetry)

DSC : Differential Scanning Calorimetry

Figure – DSC apparatus and inside (Wikipedia)

DSC : Differential Scanning Calorimetry

Figure – Power-compensation DSC

DSC : Differential Scanning Calorimetry

Figure – Heat-flux DSC

DSC : Differential Scanning Calorimetry

Figure – DSC curve for paracetamol

Clapeyron equation : presentation

∆Hm fus Tfus