Towards Crystallization Using a Strong Electric Field

Towards Crystallization Using
by Norbert Radacsi
Delft University of Technology
Co-authors: A.E.D.M. van der Heijden, J. H. ter Horst
a Strong Electric Field

Norbert Radacsi - Towards Crystallization Using a Strong Electric Field
Electric field effects?
• 5.6✕ 105
V m-1
• Cooling crystallization
• 1,4-dioxane (non-polar, D = 0.45 Debye)
1

Model compounds
• Isonicotinamide (polar molecule, D = 3.56 Debye)
• Niflumic acid (polar molecule, D = 2.43 Debye)
• 4-hydroxybenzoic acid (polar molecule, D = 2.8 Debye)
2

Theory
3
Solution
Suspension
Induced
Convection
7 kV5 kV4 kV
PrincipleAction Phenomenon Lead
Growth
rate change
Change of
Polymorph
Pr
qu
co
Pa
Sep
Tech
Cr
Nuc
Under
In
Produc
Tech
Organic
Compound &
Solvent
Electric
Field

Orientation of molecules by electric
field
A. Ziabicky, L. Jarecki, Macromol. Symp. 1996, 104, 65 – 87.
- Orientation can change the fraction of collisions successful attachment of molecules to the nucleus
τ max = pE max
Isonicotinamide:7.28 ✕ 10-24 Nm
4

Electric field effect on nucleation
work and rate
cε=3ε0εm(εc-εm)vo/2(εc+εm)
W*= 16πvo
2γ3/3(Δµ+cεE2)2
D. Kashiev, Nucleation: Basic Theory with Applications, Butterworth-Heinemann, Oxford, 2000.
Js = zf*C0 exp [-B/( kTlnS+cεE2)2]
5

Electric field effect on nucleation
work and rate
cε=3ε0εm(εc-εm)vo/2(εc+εm)
D. Kashiev, Nucleation: Basic Theory with Applications, Butterworth-Heinemann, Oxford, 2000.
εc > εm
εc < εm
εc = εm
W* decreased
W* increased
W* unchanged
6

Norbert Radacsi - Towards Crystallization Using a Strong Electric Field 7
Experimental setup #1
Text
Raman Spectroscope
Raman Probe
Crystalline
Camera System
DC Power Supply
Crystalline Particle Viewer with Raman Spectroscope
Sample in the vial
E ≦ 5.6 x 105 V/m

Experiment temperature profile
Time (min)
Solution becomes
clear
Electric field turned ON
Constant T, S, E
5oC/min
8

Visualization - crystals
Crystals grew on
the
Hammadi, Z.; Astier, J.P.; Morin, R.; Veesler, S., Crystal Growth & Design, 2009, 9, 3346 – 3347.
9
anodecathode
Changing the polarity
NIF A
4-HB A
INA
in situ product removal!

Visualization - Induction time
probability measurement
• Isonicotinamide
• Preliminary induction time probability shows increase in +DC mode
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
0 10 20 30 40 50 60 70 80
P(t)
t [min]
With E
Without E
10

• Crystal growth rate in the presence of the E field: 126 µm/min
• Crystal growth rate in the absence of the E field: 8.3 µm/min
Visualization - Crystal Growth Rate
- Isonicotinamide
With E Without E
15 x
Real time:
20 min
11

Summary - Crystal growth rate
• Growth rate of isonicotinamide & 4 hydroxybenzoic acid increased!
12

• Isonicotinamide • 4 Hydroxybenzoic acid
0 kV1 kV2 kV3 kV4 kV5 kV6 kV7 kV8 kV
Visualization - Suspension
13

Polymorph control of isonicotinamide
• 6 polymorphs (form II is the stable form)
form II form I, III, IV, V
14
• Polymorphism of niflumic acid and 4-hydroxybenzoic acid is
not influenced by the used electric field

Cooling crystallization experiments
• By recrystallizing isonicotinamide in 1,4-dioxane:
form I
Head-to-tail
no E
15

Crystal structure - Raman
spectroscopy
16

Cathode
Norbert Radacsi - Towards Crystallization Using a Strong Electric Field 17
Experimental setup #2
Parallel plate setup
Anode
+-
E ≦ 5.6 x 105 V/m
Natural cooling!

Current measurement
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 1 2 3 4 5 6 7 8 9 10
Current[µA]
Potential difference [kV]
18
Potential difference [kV]
Current[µA]
10 mA

Crystal structure - X-ray Powder
Diffraction
Table - XRPD
Without electric
field
With electric field
Polymorph Form I Form II
19

Redox reactions?
20
• No bubble formation
• Solution NMR showed the original compound
• ICP - copper content in solutions:
• Isonicotinamide: 0.0 ppm
• Niflumic acid: 0.93 ppm
• 4-hydroxybenzoic acid: 0.24 ppm
0.08 ppm

Summary
Without E With +E
Crystal
location
In situ product
removal
Crystal
growth
rate
8.3 µm/
min
126 µm/
min
Increased
Induction
time p=1
10 min 72 min Decreased(?)
Polymorph form I form II Changed

Electromigration
+
+-
+
-
+-
+-
Electromigration is the transport of molecules towards an electrode caused by the electric field
Anode
22

Increased local supersaturation
ratio
23
15 =
K(SE −1)2
K(S0 −1)2
SE = 5.06 (2.5x higher)
R = K(S −1)2

Recrystallizing isonicotinamide at
different concentrations
24

Conclusions
• Electric fields affect crystallization
• Control of crystallization (localized growth, induction
time, polymorphism)
• Increased local supersaturation - electromigration

⎟
⎟
⎠
⎞
⎜
⎜
⎝
⎛
−=
STk
cv
CfzJ 233
332
0
27
4
0
ln
exp**
γξ
Interfacial
energy
Concentration of
nucleation sites
Supersaturation
Activity
factor
Classical Nucleation Rate Expression
Attachment
frequency
2
exp
ln
B
J AS
S
⎛ ⎞
= −⎜ ⎟
⎝ ⎠
D. Kashiev, Nucleation: Basic Theory with Applications,
Butterworth-Heinemann, Oxford, 2000.

[ppm]9.0 8.5 8.0 7.5
[rel]051015
8.7186
8.7051
8.2332
7.7675
7.7525
7.7118
2.0000
0.9715
2.9943
isonicotineamide
Radacsi 1 1 D: nmrsu
Answer:
Solution NMR

Crystal structure - DSC
60 70 80 90 100 110 120 130 140 150 160 170 180
Temperature [°C]
20
mW
Manufacturer
Recrystallized in the absence of the electric field

Towards Crystallization Using a Strong Electric Field

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