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

Colloque Chimie durable, ENS Lyon, 18-19 Septembre 2012

Institut de Chimie et de Biochimie Moléculaire et Supramoléculaires

2

Génie Enzymatique, Membrane Biomimétiques et Assemblages Supramoléculaires

(GEMBAS) – Prof. L. BLUM

Organisation et Dynamique des Membranes Biologiques

(ODMB) – Prof. R. BUCHET

ICBMS Director: Prof. L. BLUM

Deputy Director: Dr. Y. QUENEAU

Catalyse, Synthèse et Environnement (CASYEN) – Prof. B. ANDRIOLETTI

Catalyse Organométallique, Synthèse et Méthodologie de Synthèse

(COSMO) – Prof. O. BAUDOIN

Synthèse de Molécules d’Intérêt Thérapeutique (SMITH) – Prof. B. JOSEPH

Synthèse, Utilisation, Réactivité des Composés Organiques et Organofluorés

(SURCOOF) – Prof. O. PIVA

Chimie Organique 2, Glycochimie (CO2GLYCO) – Prof. JP. PRALY

Chimie Organique et Bioorganique (COB) – Dr. Y. QUENEAU

Chimie Supramoléculaire Appliquée (CSAp) – Prof. H. PARROT Sy

nthè

se, M

étho

dolo

gie

et C

atal

yse

Biomolécules: Synthèse,

Propriétés et Assemblages

Mem

bran

es,

Bioc

atal

yse 174 people including :

• 84 staff 58 CNRS + Univ. Researchers 26 Technicians

• 90 non permanent Researchers 63 PhD + post-docs

The Current Situation with Solvents

3

Wordwide solvent market: 20 000 kT/year

• EU: 5000 kT/year

• France: 600 kT/year)

Current market in France:

• Oil-based: 600 kT

• Green solvents 15 kT

Forecast for 2015:

• Green solvents: 50 kT,

• Oil-based: 500 kT

NA26%

EU27%

Asia/Pacific31%

ROW16%

NESOREACH Project

4 ANR CPDD “Nesoreach” 2009-2013

Develop a fast and reliable method for predicting the toxicological and eco-toxicological properties of the most commonly used solvents:

• compile a database containing the main chemical, physical, toxicological and eco-toxicological 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, • Applicative tests, • Up-scaling.

Le vernis est émaillé dans un four d émaillage qui peut être horizontal ou vertical selon le diamètre du fil.

Cooling zone(8-20 passes)

ControlPolymerisation oven

VarnishApplication Wire stretching

winding

Oven temp(400-750°C)

Study Case

5

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).

Biosourced

or

Non-toxic petroleum based solvent

Resin solubilisation Mechanistic role

Heat capacity

Boiling point Cost constraints

Toxicity

NESOREACH Project: Consortium

6

Prof. ANDRIOLETTI ICBMS-UMR 5246 Université Lyon 1

Prof. LANTERI LSA-UMR 5180 Université Lyon 1

C. CREN SCA-USR59 Solaize

V. MERCIER Essex IVA Meyzieu

ANR CPDD “Nesoreach” 2009-2013

Substitution of solvents within the frame of REACH

Data analyses

Description : • PCA • Classification methods

Physico-chemical descriptors

Theoretical descriptors

Eco-toxicological descriptors

Toxicological descriptors

Solvent database

Modelling • QSAR QSPR relationships

Data analyses

Description : • PCA • Classification methods

Developing a Database: Scientific Approach

A. Levet, SCA/LSA 7

• 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)

Compiling the Solvent Database (1)

A. Levet, SCA/LSA 8

• 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…

Compiling the Solvent Database (2)

A. Levet, SCA/LSA 9

• Ecotoxicological descriptors (Records in dedicated databases and validated by INERIS)

• EC50 Fish • EC50 Invertebrate • EC50 Algaes

• Using of the database : (in progress)

• Development of QSAR models to predict solvent EC50 • Establishment of a solvents classification

Fish 161

Algae 124

Invertebrate 157

121 151

122

120

Compiling the Solvent Database (3)

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 %

-6

-4

-2

0

2

4

6

-8 -6 -4 -2 0 2 4 6 8

F2 (1

4%)

F1 (76%)

Observations (F1 and F2 axes: 91%)

1

2

3

4

Most important descriptors : • Water solubility • Log P • δh Hansen parameters

Less toxic More toxic

Example : EC50 Fish

Limitations : non homogeneous classes

A. Levet, SCA/LSA 11

Solute Solvent Non solvent

• Purpose : • Experimental determination of Hansen solubility parameters (δd,

δp, δh) of polymers • Determination of solvents for polymers solubilization

• Process Solubility tests in 52 solvents (visual observation)

Soluble Partially soluble

Non- soluble

Solubility Tests

A. Levet, SCA/LSA 12

• 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

Solubility tests

A. Levet, SCA/LSA 13

• PAI Solvents 3

Partial solvents 5

Non solvents 44

PAI

Data exploitation : No substitution solvent identified Test of solvent mixtures (In progress)

Solubility tests

A. Levet, SCA/LSA 14

Purpose : • Quantifying the amount of polymer dissolved in solution evaluation of solvent mixture

Polymer analysis by ATG, ATG-TD-GC-MS, IR

PAI and PEI seem to degrade before the temperature evaporation of the solvents : No quantification possible by ATG

Temperature ramp 10°C/min 25°C to 1000°C

Polymer Analysis: ATG

A. Levet, SCA/LSA 15

• Polymer analysis by measuring nitrogen (In progress)

Encouraging preliminary tests for the quantification of PEI • Polymer analysis by MALDI-TOF (In progress)

Development and validation of the method on a test polymer Use of an internal standard

0.0

0.5

1.0

1.5

2.0

2.5

5x10

Inte

ns. [

a.u.

]

1000 2000 3000 4000 5000m/z

Internal standard

Test polymer

Problem of reproducibility

y = 0,0523x - 0,0002 R² = 0,9837

0

0,001

0,002

0,003

0,004

0,005

0,006

0,007

0,008

0,009

0,01

0 0,05 0,1 0,15 0,2

I Pol

ymer

/ I

Inte

rnal

stan

dard

Polymer conc (mg/mL)

Polymer Analysis: Quantitative MALDI-TOF

A. Levet, SCA/LSA 16

Solvent Substitution and Mechanistic Investigations

17

OCN N

O

O

HN

O

NO

O

O

O

N

ONH

OH

O

O

Mechanistic studies with in situ IR

Solvents60-85%

mixture of solvents

Additivesfew%

Raw materials (oligomers)15-40%

- catalysts,- adhesion promoters,- accelerators,- surfactants,- wetting agents.- ...

- naphta solvents,- xylene,- NMP,- DMAc,- Cresol C40,- Xylenol,- Phenol- ...

NON-toxic solvents60-85%

Additivesfew%

New "green"class of enamels

Raw materials (oligomers)15-40%

Our goal

Typical structure of a PAI

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

Our Strategy

18

OCN N

O

O

HN

O

NO

OHN

O

N

ONH

OH

O

O

NH

ONH2+

O ClEt3N

EtOAc0°C->25°C

NH2O

O

O

air, 160°C

1 hourN

O

O

+

N

O

O

OHN

NH2O

O

O

N

O

O

COOH

1) AcOH

2) SOCl2 COCl

+ Et3N, PhNH2

EtOAc0°C->25°C

Benzanilide,

Benzylphtalimide

1,3-dioxo-N,2-diphenyl isoindoline-5-carboxamide

93%

91%

100%

64%

The Building Blocks

L. Sandjong Kuigwa, F. Szydlo, ICBMS 19

Substrate IR vibration Wavelength (cm-1)

Solution ATR

TMA

C=O stretch anhydride C=O stretch acide C-O-C stretch C-O et C-C stretch C-H ar def.

1780 1628 1231

884-921 721

1774

1226

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

1724 1654 1376

IR Signature of the Building Blocks

Bruker, MATRIX-MF FT-IR

L. Sandjong Kuigwa, F. Szydlo, ICBMS 20

NCO

C=O amide PAI

C=O carboxylic acid of TMA

C=O imide PAI

C=O anhydride of TMA

C-N PAI

C-O acid of TMA

IR reference t=0min after addition of the starting materials

Conditions: Air, NMP not distilled

Identification of the Characteristic IR Bands of a PAI

L. Sandjong Kuigwa, F. Szydlo, ICBMS 21

NCO

NO+

80°C??

PhNCO aromatic protons

CH3 NMP

3x(CH2) NMP

NCO

NO+

80°C??

Conclusion: At 80°C, no interaction between PhNCO and NMP is evidenced

Understanding the Role of the Solvent at 80°C

L. Sandjong Kuigwa, F. Szydlo, ICBMS 22

NCO

NO+

140°C??

Complex aromatic region

CH3 NMP

3x(CH2) NMP

Conclusion: At 150°C, many new signals appear (and/or disappear in NMR or IR) ⇒ clear reaction between NMP and PhNCO

Disappearance of the NCO stretching band

T0

T200min

In the industrial conditions, NMP plays a role of non-reactive solvent.

Understanding the Role of the Solvent at 150°C

L. Sandjong Kuigwa, F. Szydlo, ICBMS 23

• 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

Towards the Synthesis of Non-Toxic PAI

1 solvent of these 2 solvents is under industrial development (Pilot Scale)

New "green"class PAI 24

Towards the Synthesis of Non-Toxic PEI

NN

O

O

O

O O

OO

ON OH

N

N

HOO

O

OO

O O

OO

O

N

O

O

N

O

O

O

OH

n

Polyesterimide (PEI)

Imide Ester

25

Cresol: A Reactive Solvent

NCOOH

1 eq 1 eq

HN O

O

T= 30 min

NCO signal

Urethane C=O band

Urethane C-N-H Band

Cresol reacts with phenylisocyanate affording the corresponding urethane.

L. Sandjong Kuigwa, ICBMS 26

Is a Reactive Solvent Required?

o The synthesis of the key intermediate can be controlled in the absence of cresol

OCN NCO

OO

O

O

OH

catalyst/solvent

1 eq 2eq

N N

O

O

O

OHO

O

OH

O

Diacid-Diamide

imide C=O band

A reactive solvent is not absolutely required

See also Patent, Bayer 659018 07/29/1965

L. Sandjong Kuigwa, ICBMS 27

Synthesis of a PEI in a non-Toxic Solvent

C=O Glycol-ester and

imide band

C=O Ester THEIC band

C=O imide band

The synthesis of the PEI in a non-toxic solvent is possible

L. Sandjong Kuigwa, ICBMS 28

• One non-toxic commercial solvent was idenfied very promising

• This solvent is commercial and at a price acceptable for the enamel market.

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

Applicative Properties

29

Main Results

30

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

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

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

1

1111 1

1

1

1

111

1

1

2

2

2

2 2

2

222

22

22

2

2 22

2

2 22

222 22

2

2 222 2

2

2

2

2

2

3 33

3

3

3 33

33

3

3

3

3

33 3

33

33

3 3

33

333

3

3

333

33

3

3

3 3

3

3

3

3

33

3

3

3

3

3 33

33

3 333

3

3

3

3

3

3

4

4

4

44

4

4

44

4

4

4

4

4

4

4

4

4

4

4

4

4 4

4

4

4

4

44

4

4

4

4

44

44

4

4

4

4

4

44

4

4

4

4

4

4

4

4

4

4

4

4

44

4

4

44

4

4

4

4

44

4

4

4

Expe

rimen

tald

ata

Predicted values

Solvant

Solvant partiel

Non solvant

PEI

ACKNOWLEDEMENTS

31

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