Colloque Chimie durable, ENS Lyon,
18-19 Septembre 2012
NESOREACH: New “eco-compatible”
REACH compliant solvents
Prof. Bruno ANDRIOLETTI
bruno.andrioletti@univ-lyon1.fr
Equipe de CAtalyse, SYnthèse, ENvironnement (CASYEN)
UMR 5246 CNRS - Université Claude Bernard Lyon1
Domaine scientifique de la Doua - Bât. CPE (Curien 308) - 2ème étage - Aile C
43 boulevard du 11 novembre 1918
69622 Villeurbanne CEDEX
1
Institut de Chimie et de Biochimie Moléculaire et Supramoléculaires
Catalyse, Synthèse et Environnement
(CASYEN) – Prof. B. ANDRIOLETTI
Catalyse Organométallique, Synthèse et
Méthodologie de Synthèse
(COSMO) – Prof. O. BAUDOIN
Chimie Organique 2, Glycochimie
(CO2GLYCO) – Prof. JP. PRALY
Chimie Organique et Bioorganique
(COB) – Dr. Y. QUENEAU
Synthèse de Molécules d’Intérêt Thérapeutique
(SMITH) – Prof. B. JOSEPH
Membranes,
Biocatalyse
Synthèse, Utilisation, Réactivité des Composés
Organiques et Organofluorés
(SURCOOF) – Prof. O. PIVA
Chimie Supramoléculaire Appliquée
(CSAp) – Prof. H. PARROT
Génie Enzymatique, Membrane Biomimétiques et
Assemblages Supramoléculaires
(GEMBAS) – Prof. L. BLUM
Organisation et Dynamique des Membranes
Biologiques
(ODMB) – Prof. R. BUCHET
Biomolécules: Synthèse,
Propriétés et Assemblages
Synthèse, Méthodologie
et Catalyse
ICBMS
Director: Prof. L. BLUM
Deputy Director: Dr. Y. QUENEAU
174 people including :
• 84 staff
58 CNRS + Univ. Researchers
26 Technicians
• 90 non permanent Researchers
63 PhD + post-docs
2
The Current Situation with Solvents
 Wordwide solvent market: 20 000 kT/year
ROW
16%
NA
26%
• EU: 5000 kT/year
• France: 600 kT/year)
 Current market in France:
• Oil-based: 600 kT
Asia/Pacific
31%
EU
27%
• Green solvents 15 kT
 Forecast for 2015:
• Green solvents: 50 kT,
• Oil-based: 500 kT
3
NESOREACH Project
 Develop a fast and reliable method for predicting the toxicological and ecotoxicological properties of the most commonly used solvents:
• compile a database containing the main chemical, physical, toxicological and ecotoxicological properties of 250 solvents,
• Select the most pertinent parameters for carrying out QSPR and QSAR analyses,
• Validate the method on chosen cases.
 Study case: the substitution of cresol, phenol and NMP in the varnish business
• Determine the mechanistic implication of the aforementioned solvents in the
synthesis of PolyAmideImides (PAI) and PolyEsterImide (PEI): reactive or non-reactive
solvents,
• Propose and substitute the toxic solvents in the syntheses of the two thermoset
polymers with REACH-compliant alternatives,
Le vernis est émaillé dans un four d émaillage qui peut être horizontal ou vertical selon le
• Applicative tests,
Varnish
Control
diamètre
du fil.
Polymerisation oven
Wire stretching
Application
• Up-scaling.
winding
ANR CPDD “Nesoreach” 2009-2013
Cooling zone
(8-20 passes)
Oven temp
(400-750°C)
4
Study Case
 NMP (2400 T/year@ IVA-Lyon) : toxic because of the deleterious effects on the development of
fetus (Reprotoxic, category 2).
 Cresol (2600 T/year@ IVA-Lyon) : toxic by skin contact and ingestion (possible irreversible effects)
(Mutagenic category 3).
 Phenol (1100 T/year@ IVA-Lyon) : toxic by inhalation, by skin contact and ingestion (possible
irreversible effects) (Mutagenic category).
Mechanistic role
Resin solubilisation
Biosourced
or
Heat capacity
Toxicity
Non-toxic petroleum based
solvent
Cost constraints
Boiling point
5
NESOREACH Project: Consortium
C. CREN
SCA-USR59
Solaize
Prof. LANTERI
LSA-UMR 5180
Université Lyon 1
ANR CPDD “Nesoreach” 2009-2013
Prof. ANDRIOLETTI
ICBMS-UMR 5246
Université Lyon 1
V. MERCIER
Essex IVA
Meyzieu
6
Developing a Database: Scientific Approach
Solvent database
Physico-chemical
descriptors
Theoretical
descriptors
Eco-toxicological
descriptors
Toxicological
descriptors
Data analyses
Data analyses
Description :
• PCA
• Classification methods
Modelling
• QSAR QSPR
relationships
Description :
• PCA
• Classification methods
Substitution of solvents within the frame of REACH
A. Levet, SCA/LSA
7
Compiling the Solvent Database (1)
• 295 solvents grouped ranked in 17 chemical families (IUPAC)
• Physico-chemical descriptors
•
•
•
•
Molecular weight,
Boiling and melting point,
Hansen solubility parameters,
Octanol/water partition coefficient (LogP) (Some
values ​confirmed by counter-current chromatography (CCC)) …
• Theoretical quantum descriptors
• HOMO and LUMO energy,
• Dipole moment,
• Electrostatic potential …
 Calculation hardness (LUMO-HOMO) and
reactivity((LUMO+HOMO)/2)
A. Levet, SCA/LSA
8
Compiling the Solvent Database (2)
• Geometric or topological descriptors calculated by two
programs:
– Prochemist
• Topological indices : Wiener, Kier, Balaban, Randic…
– Sybyl
• Molecular volume and surface area,
• Atom and binding numbers…
A. Levet, SCA/LSA
9
Compiling the Solvent Database (3)
• Ecotoxicological descriptors
(Records in dedicated databases and
validated by INERIS)
• EC50 Fish
• EC50 Invertebrate
• EC50 Algaes
Fish
161
151
Invertebrate
157
120
122
121
Algae
124
• Using of the database : (in progress)
• Development of QSAR models to predict solvent EC50
• Establishment of a solvents classification
A. Levet, SCA/LSA
10
Preliminary Results: Predicting an Eco-toxicological Class
• Discriminating Factorial Analysis (AFD)
% Correct
EC50 Fish
78,1 %
EC50 Invertebrates
75,8 %
EC50 Algaes
72,0 %
Observations (F1 and F2 axes: 91%)
Less toxic
More
toxic
4
2
F2 (14%)
Most important descriptors :
• Water solubility
• Log P
• δh Hansen parameters
6
1
0
2
3
-2
Limitations : non homogeneous classes
4
-4
-6
-8
A. Levet, SCA/LSA
-6
-4
Example : EC50 Fish
-2
0
F1 (76%)
2
4
6
8
11
Solubility Tests
• Purpose :
• Experimental determination of Hansen solubility parameters (δd,
δp, δh) of polymers
• Determination of solvents for polymers solubilization
Soluble
Solute
Partially
soluble
Nonsoluble
Solvent
Non solvent
• Process
Solubility tests in 52 solvents (visual observation)
A. Levet, SCA/LSA
12
Solubility tests
• PEI
Solvents
12
Partial solvents
15
Non solvents
25
PEI
Data use:
List of potential solvents with suitable eco-toxicological parameters, solubility tests
 Identification of the suitable substitution solvent
A. Levet, SCA/LSA
13
Solubility tests
• PAI
Solvents
3
Partial solvents
5
Non solvents
44
PAI
Data exploitation :
No substitution solvent identified
Test of solvent mixtures (In progress)
A. Levet, SCA/LSA
14
Polymer Analysis: ATG
 Purpose :
• Quantifying the amount of polymer dissolved in solution  evaluation of solvent
mixture
 Polymer analysis by ATG, ATG-TD-GC-MS, IR
Temperature ramp
10°C/min
25°C to 1000°C
 PAI and PEI seem to degrade before the temperature evaporation of
the solvents : No quantification possible by ATG
A. Levet, SCA/LSA
15
Polymer Analysis: Quantitative MALDI-TOF
• Polymer analysis by measuring nitrogen (In progress)
Encouraging preliminary tests for the quantification of PEI
• Polymer analysis by MALDI-TOF (In progress)
0,01
x10 5
2.5
I Polymer / I Internal standard
Intens. [a.u.]
Development and validation of the method on a test polymer
Use of an internal standard
Internal standard
2.0
1.5
Test polymer
1.0
y = 0,0523x - 0,0002
R² = 0,9837
0,009
0,008
0,007
0,006
0,005
0,004
0,003
0,002
0,001
0
0
0,05
0,1
0,15
0,2
Polymer conc (mg/mL)
0.5
0.0
1000
2000
3000
4000
5000
m/z
A. Levet, SCA/LSA
Problem of reproducibility
16
Solvent Substitution and Mechanistic Investigations
HN
O
O
N
OCN
N
O
O
O
OH
NH
O
O
N
O
O
O
Typical structure of a PAI
Mechanistic studies
with in situ IR
Raw materials (oligomers)
15-40%
Additives
f ew %
- catalysts,
- adhesion promoters,
- accelerators,
- surf actants,
- wetting agents.
- ...
Solvents
60-85%
mi x t ure of sol vent s
- naphta solvents,
- xylene,
- NMP,
- DMAc,
- Cresol C40,
- Xylenol,
- Phenol
- ...
Raw materials (oligomers)
15-40%
Additives
f ew %
NON-toxic solvents
60-85%
Our goal
New "green"
class of enamels
17
Our Strategy
 In situ and ex situ IR analyses
• IR spectra of the building-blocks
• IR « fingerprint » of a PAI in NMP/PEI in cresol and identification of the
characteristic bands = IR reference
• IR of PAI/PEI synthesized using the new solvents and comparison with the
reference IR.
 Determine the mechanism of the polymerization
• Use phenylisocyanate as model
• Determine the need for (non)-reactive solvents
18
The Building Blocks
HN
O
O
N
OCN
N
O
O
O
O
O
H
N
N
O
O
O
NH2
Cl
O
Et3N
+
EtOAc
0°C->25°C
Benzanilide,
N
H
91%
O
O
NH2
Benzylphtalimide
air, 160°C
+
OH
NH
N
O
1 hour
O
O
O
NH2
+ O
N
O
1) AcOH
Et3N, PhNH2
N
COOH 2) SOCl2
O
O
100%
COCl
O
93%
L. Sandjong Kuigwa, F. Szydlo, ICBMS
EtOAc
0°C->25°C
O
HN
O
1,3-dioxo-N,2-diphenyl
isoindoline-5-carboxamide
64%
19
IR Signature of the Building Blocks
Substrate
IR vibration
Wavelength (cm-1)
Solution
ATR
1780
1628
1231
884-921
721
1774
TMA
C=O stretch anhydride
C=O stretch acide
C-O-C stretch
C-O et C-C stretch
C-H ar def.
MDI
NCO stretch
2266
2260
Benzanilide
C=O stretch
1655
1653
Benzylphtalimide
C=O stretch
C-N stretch
1716-1735
1377
1703-1734
1382
C=O phtalimide
C=O anilide
C-N stretch
L. Sandjong Kuigwa, F. Szydlo, ICBMS
1226
1724
1654
1376
20
Bruker, MATRIX-MF FT-IR
Identification of the Characteristic IR Bands of a PAI
C=O amide PAI
C=O imide PAI
C-N PAI
C=O anhydride of
TMA
C=O carboxylic acid of
TMA
NCO
C-O
acid of TMA
Conditions: Air, NMP not distilled
IR reference t=0min after addition of the starting materials
L. Sandjong Kuigwa, F. Szydlo, ICBMS
21
Understanding the Role of the Solvent at 80°C
NCO
+
O
80°C
??
N
NCO
+
O
80°C
??
N
CH3
NMP
PhNCO aromatic
protons
3x(CH2)
NMP
Conclusion: At 80°C, no interaction between PhNCO and NMP is evidenced
L. Sandjong Kuigwa, F. Szydlo, ICBMS
22
Understanding the Role of the Solvent at 150°C
NCO
+
CH3
NMP
Complex
aromatic region
O
140°C
??
N
T0
Disappearance of the
NCO stretching band
3x(CH2)
NMP
T200min
Conclusion: At 150°C, many new signals appear (and/or disappear in NMR or IR)
⇒ clear reaction between NMP and PhNCO
In the industrial conditions, NMP plays a role of non-reactive solvent.
L. Sandjong Kuigwa, F. Szydlo, ICBMS
23
Towards the Synthesis of Non-Toxic PAI
• Two main solvent suppliers provided new developed solvents under secrecy
agreement with IVA and CASYEN:
• Three solvents were identified as technically suitable to substitute NMP
• Syntheses of PAI: OK (CASYEN)
• Enamelling and magnet wires properties: OK (IVA)
• Issue 1 = results of toxic evaluation (May 2012): Among the 3 most promising
solvents, 2 were shown non toxic (Partial results-90% )
• Issue 2 = accessibility
1 solvent of these 2 solvents is under industrial development (Pilot Scale)
New "green"
class PAI
24
Towards the Synthesis of Non-Toxic PEI
O
HO
N
O
O
N
N
O
O
N
O
O
O
O
O
Ester
Imide
N
O
O
O
O
O
O
O
O
N
O
OH
O
O
OH
N
O
n
Polyesterimide (PEI)
25
Cresol: A Reactive Solvent
NCO
OH
H
N
O
O
1 eq
1 eq
NCO signal
Urethane C=O
band
Urethane C-N-H
Band
T= 30 min
Cresol reacts with phenylisocyanate affording the corresponding urethane.
L. Sandjong Kuigwa, ICBMS
26
Is a Reactive Solvent Required?
O
O
O
O
NCO
OCN
catalyst/solvent
O
OH
1 eq
O
HO
2eq
O
N
N
O
O
O
OH
Diacid-Diamide
See also Patent, Bayer 659018 07/29/1965
imide C=O
band
o The synthesis of the key intermediate can be controlled in the absence of cresol
L. Sandjong Kuigwa, ICBMS
A reactive solvent is not absolutely required
27
Synthesis of a PEI in a non-Toxic Solvent
C=O imide
band
C=O
Glycol-ester and
imide band
C=O
Ester THEIC band
The synthesis of the PEI in a non-toxic solvent is possible
L. Sandjong Kuigwa, ICBMS
28
Applicative Properties
• One non-toxic commercial solvent was idenfied very promising
19960 MC40
OFA627
Reference in Cresol & phenol
In solvent D
Bare wire diameter (mm)
0,501
0,501
Insulation increase (mm)
0,044
0,043
Speed (m/mm) (machine = HRE)
130
130
Flexibility (%) (1D)
20%
20%
Cut-through (°C) (IEC 100x100)
340
350
Tangent Delta (°C)
197°C
200°C
• This solvent is commercial and at a price acceptable for the enamel market.
29
Main Results
5.0
4
4.5
4.0
Solvant partiel
3.5
Non solvant
3.0
PEI
Experimental data
Solvant
4
4
2.5
2.0
1.5
3
1.0
2
0.0
22 2
2
2
222
2
22 2
2
22
1 1
44
4
4
2
0.5
4
44
4
4
4
4
4
4
4 4 4 44444 4 44 4 4
4 44
4
4 44 44 4 4 44
4
4
4
4
44
4
44
44
44 4
44
4 44 4 4
33 43
33 3
3 333 33 3 3
3
33
3 3333
3
3 3 3
3
3
3 33 3 3 3
3
33 3 33 3 333 3 3 3
3
3
3
3
3
3 33 3
3
3
33
33
22 2
2
2 2
2 2
4 4
4
4
4
2
2
2
2 22
2
1
1
1
1
11
-0.5
2
2
2
2
2
1
1
1
1
-1.0
-1.5
1
1
-2.0
-2.0
-1.5
-1.0
-0.5
0.0
1) Mechanistic investigations on the synthesis of the PAI and the PEI
 (Spectroscopic) identification of the key intermediates: done
 Determination of the mechanisms of formation of PAI and PEI: done
0.5
1.0
1.5
2.0
Predicted values
2.5
3.0
3.5
4.0
2) Syntheses of PAI and PEI in new non-toxic solvents
 PAI: Industrial development of new, suitable solvents compatible with lab-scale
syntheses of PAI
 PEI: A suitable, existing non-toxic solvent has been identified: next step: 100 kg
lab scale experiment planned fall 2012.
 Synthesis of partly bio-sourced solvents (patent in preparation)
3) Solvent prediction
 A database gathering 17 main physico-chemical and (eco)-toxicological
properties of 295 solvents has been compiled;
 A predictive method displaying promising preliminary results is implemented;
 Solubility tests using Hansen’s parameters have been carried out
30
4.5
5.0
ACKNOWLEDEMENTS
E. Framery, F. Szydlo, L. Sandjong-Kuigwa
Equipe de Catalyse, Synthèse et Environnement, CASYEN-ICBMS, Université Lyon 1
P. Lantéri, A. Levet, C. Bordes, A. Berthod, H. Chermette, J.-Y. Gauvrit, P. Mignon
Laboratoire des Sciences Analytiques, Université Lyon 1
C. Cren-Olivé
Service Central d’Analyse, CNRS Solaize
F. Andrioletti, V. Mercier (Essex-IVA)
L. Chancerelle, L. Geoffroy
INERIS, Verneuil-en-Halatte
31