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A. Stolle,
Sustainable Coatings ConferenceDuesseldorf, June 18-19, 2013
Ball Milling for organic synthesis: A tool for process intensification with regard to
energy efficiency and economy of scale
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
General strategies for process intensification
A B C D
educts synthesis work-up product(s)
A B
solvent(s),catalyst(s),
…
refeeding
A B C
refeeding
product-integration
DA B C D
eductseducts synthesissynthesis work-up product(s)product(s)
A B
solvent(s),catalyst(s),
…
solvent(s),catalyst(s),
…
refeeding
A Brefeeding
A B C
refeedingrefeeding
product-integrationproduct-
integration
DD
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
General strategies for process intensification
Optimize an existing reaction / process. Implementation of alternative solvents / reagents
with enhanced possibility for recycling Alternative reactor / process technology Alternative synthesis concepts …
time, effort,
complexity
Heating through convection Photochemistry Electrochemistry Dielectric heating Mechanical stress
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Terminology
M. C. Leah(1823-1897)
founder ofmechanochemistry
W. Ostwald(1853-1932)
definition ofmechanochemistry
Mechanochemistry / Tribochemistry: Breakage of covalent, ionic, or coordinative bonds as well as crystal lattices on mechanical stress.
Ball milling / Grinding: Technical method for the induction of mechanical stress and particle size refinement.
18th century: mortar & pestle today: ball mills
IUPAC Compendium of Chemical Technology (the "Gold Book"), Blackwell Scientific Publications, Oxford, 1997.Takacs, J. Mater. Sci. 2004, 39, 4987.
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Pd(OAc)2KF-Al2O3
solvent-freeBr
AcAc
phenyl-boronic acid
Schneider et al., Green Chem. 2009, 11, 1894.
Ball mills have a higher reproducibility then reactions carried out with mortar and pestle. Furthermore, the process stability is increased and tools for process control are available.
“Reagents were triturated in a mortar with pestle for the required reaction time“: min - hours?!
6%
64%
94%
0%
25%
50%
75%
100%
200 rpm 400 rpm 800 rpm
chem
ical
yie
ld
ball milling at different rot
mortar+
pestle
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Fields of Application
Fabrication of catalysts (metastable phases, composite catalysts, nanoparticles)
Mechanical alloying (composite materials, alloys, metastable materials)
Particle refinement and homogenization (glass, cellulose, plastics, powders…)
Ore refinery (iron ore, copper ore, gold, …)
Cracking or activation of bacteria
Degradation of dioxins, dehalogenation
Analytics (drugs, metal, waste, …)
Inorganic and Organic Synthesis
G. Kaupp, Top. Curr. Chem. 2005, 254, 95; James et al., Chem. Soc. Rev. 2012, 41, 413.
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
5 mol% Pd(OAc)2, 2.5 equivalents NaHCO3, 0.2 equivalents HCO2Na,1.2 equivalents nBu4NCl, NaCl; milling time = 60 min.
Frejd et al., J. Organomet. Chem. 2004, 689, 3778.
Technique Yield [%]Planetary ball mill (stainless steel, 13.3 Hz) 77
Heating in a test tube (80 °C) 18
Heating and stirring in a test tube (80 °C) 33
Hydraulic press with preheated anvil (80 °C, 19.6 MPa) 13
The Mizoroki-Heck reaction
NHBoc
CO2R1
R1 = Bn, Me
5 mol% Pd(OAc)2NaHCO3, HCO2Na, nBu4NCl
+ R-X
planetary ball millstainless steel1 h; 13.3 Hz
NHBoc
CO2R1
R10 examples:13-88% yield
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
chemistry
…
ballpowder
materialdensity
numberof milling
balls
time
frequency
Chemical parameters– Reaction type, mechanism – Reagents, milling auxiliary (EY)– LAG (, )
Technological parameters– Type of ball mill– Material density – Number of grinding bodies nMB
– Diameter of grinding bodies dMB
– Filling degree , ()
Process parameters– Frequency , peripheral velocity vp
– Milling time t
Energy intensity Em, degree of efficiency el
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
dSD = diameter of the sun disc
dbeaker = inner diameterof the milling beaker
d = distance ofrotation axis
PBM
A = amplitude
MBM VBM
Ax
Az
Ay
planetary ball mill mixer/vibration ball mill
2 2 2 2(rot,osc) 22 2kin kinm IE v E I
Suryanarayana, Progr. Mat. Sci. 2001, 46, 1.Takacs, Progr. Mat. Sci. 2002, 47, 355.Baláz, in Mechanochemistry in Nanoscience and Minerals Engineering, Springer-Verlag, Berlin, 2008, pp. 103.
Ball mills for lab-applications
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
1
,3 2,
,
1 Y feedstress feed MB p MB
Y MB
EE d v
E
Estress,feed = stress energydMB = diameter of milling balls
vp = peripheral speed MB = density of milling balls
laboratory: planetary ball mill continuous operated stirred media mill
Rosenkranz et al., Powder Technol. 2011, 212, 224. Becker et al., Int. J. Miner. Process. 2001, 61, 189.
Scale-up and modeling
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Scale-up and modeling
German Federal Environmental Foundation
Fritsch GmbH
RessourcenEffiziente chemische Synthese – ProzessEntwicklung in Kugelmühlen für lösungsmittelfreie ReakTionen (RESPEKT)
TU BraunschweigFSU Jena
Zoz GmbH
With Evonik Degussa GmbH as associated industrial partner
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
No general correlation Has to be checked for specific
reaction. Influence of reaction kinetic (k, Ea, T) No intercorrelation between and t
measurable. Yield proportional to 2 and t
Szuppa et al., ChemSusChem 2010, 3, 1181.Stolle et al., Chem. Soc. Rev. 2011, 40, 2317.
OKMnO4Al2O3, H2O
PBMMSZ
Frequency and milling time t
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
energy intensity Em
Suzuki reaction: Green Chem. 2009, 11, 1894. aniline homo-coupling: Chem.-Eur. J. 2010, 16, 13263. Glaser reaction: Chem.-Eur. J. 2011,
17, 8129. Knoevenagel condensation: Green Chem. 2008, 10, 767.
Correlation to other methods of mechanical activation (cavitation). Radiation-based
methods (e.g. µw) show higer Em.
NH2
KMnO4N
NPhPh
1 10 100 1000
planetary ball mill
mixer ball mill
classic heating
microwave (multimode)
microwave (monomode)
ultrasound
E m [kWh mol-1]without cooling
with cooling
,
gridm
product ii
EE
n
Proven for several organic reactions:– Suzuki-Miyaura cross-coupling– Homo-coupling of aniline – Glaser reaction – Knoevenagel condensation – …
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Application in organic synthesis
Redox reactionsMetal-catalyzed reactions
Aldol-type reactionsSynthesis of heterocyclesCarbohydrate chemistry
Peptide synthesisEnantioselective synthesis
Fullerene chemistryDehalogenation
…
A huge variety of organic synthetic transformations have beenreported so far applying ball milling chemistry conditions:
Recent reviews:Stolle et al., Chem. Soc. Rev. 2011, 40, 2317.James et al., Chem. Soc. Rev. 2012, 41, 413.
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
1st referenced reaction type (organo)catalyst2000 Suzuki-Miyaura Pd(PPh3)4
2003 Suzuki-Miyaura Pd(AcO)2, NEt32004 Aldol-type reaction Mn(AcO)3
2004 Mizoroki-Heck Pd(AcO)2
2007 asymmetric aldol reaction BINAM-prolinamide or proline
2008 Suzuki-Miyaura Pd(AcO)2, KF-Al2O3
2009 Sonogashira Pd(PPh3)4 / Cu-cocatalyst
2010 Sonogashira Pd(AcO)2 / DABCO
2011 Glaser Cu-, Ni- or Co-catalyst
2011 CuAAC Cu-catalyst
under construction Chan-Lam Cu-catalyst
under construction hydroamination heavy group VIII transition metals
Recent reviews:Rodriguez et al., Adv. Synth. Catal. 2007, 349, 2213.Stolle et al., Chem. Soc. Rev. 2011, 40, 2317.Stolle, Bolm et al., in Innovative Catalysis in Organic Synthesis (Ed. P. Andersson), Wiley-VCH, Weinheim 2012, 327-350.
Catalysis in ball mills
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
R1 R2
alkynesR1 R3
Pd-catalystaryl halide
R2 = H
Sonogashiracross-coupling
R1 R1
Glaser homo-coupling
Cu-catalystoxidant
R2 = H
NN
N
R1
R3
CuAACreaction
Cu-catalystazide
R2 = H
sec. amine
R = Me or EtR2 = H, CO2R
N
RO2C
R2
enamine formationH
NaX,Oxone
R2 = H,Ph; X = Cl, Br
R1 = Ph
PhR2
X
XPh
R2O
X
+
X
(oxidative) halogenation
dieneAlCl3
RR1
R2
Diels-Alder reaction
R1,R2 = CO2MeR = H, Me
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Ball mills are devices developed for particle refinement + desagglomeration. continuous generation of fresh surfaces with high defect concentration
Ball mills are scalable from mL- to m3-scale for lab and industry applications. High mixing efficiency helps to overcome mass-transport-limitations. Direct energy entry by friction and impact Robustness and reproducibility (Figure 1)
Solid-state reactions in the field of Organic Synthesis Parameters are classified into:
– chemical parameters, technological parameters, and process parameters.
Performance of reactions depends on various reaction parameters:
– frequency, material density, filling degree, and many more (Figure 2).
Degree of efficiency depending on type of ball mill and reaction scale.
High energy efficiency compared to synthesis with other methods of energy entry (classical as well as non-classical)
6%
64%
94%
0%
25%
50%
75%
100%
200 rpm 400 rpm 800 rpm
chem
ical
yie
ld
ball milling at different rot
mortar+
pestleFigure 1
Figure 2
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Speed-up of reactions Intensive mixing efficiency Low energy intensity Lowering the risk potential Decrease of solvent intensity Up-scaling of the reactions possible
Still to come:- Continuous chemical reactions- Temperature and pressure control- Harmonization of reaction variables
All solutions have a solvent (T. Welton), unless they utilize ball mills.
Welton, Green Chem. 2006, 8, 13.
Take home message
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Thank you foryour attention!
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
Thank you foryour attention!
Chem. Soc. Rev. 2011, 40, 2317.
Achim StolleSustainable Coatings Conference
Duesseldorf, June 18-19, 2013
material hardness[Vickers]
density[g cm-3]
energy entry possible impurities in product
stainless steel ~ 550 7.8 high Fe, Cr
hardened steel ~ 750 7.9 high Fe, Cr, C
tungsten carbide ~ 1200 14.8 very high WC, Co
agate ~ 1000 2.7 very low SiO2
corundum ~ 1750 3.9 low (Al2O3, SiO2)
MSZ / YSZ ~ 1200 5.9 moderate (ZrO2, MgO, Y2O3)
PTFE elastic 2.1 very low F, C
2
2kinmE v
The material density determines the • energy density,• material abrasion, and • cross contamination.
Materials for grinding bodies