mechanochemistry: solvent‐free organic reacons in the solid … · 2009. 3. 5. · outline •...
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Mechanochemistry:Solvent‐FreeOrganicReac8onsintheSolidPhase
PeterM.LambertMarch4th,2009
DepartmentofChemistryMichiganStateUniversity
1
Outline
• Introduc8ontomechanochemistry• Organicmechanochemicalreac8ons– Oxida8onofalkenes– Amideforma8on– Nitronesynthesis– Asymmetricinduc8on
– Cellulosefunc8onaliza8on• Conclusion
2
TypesofChemistry
• Mechanochemistry– physicalac8va8on
3J.Fernández‐Bertran,PureAppl.Chem.,1999,71,581‐586.
• Electrochemistry– electricalac8va8on
• Photochemistry– lightac8va8on
• Thermochemistry– heatac8va8on
Combus<on
• Rubbings8ckstogethertomakefire• Combus8onstartsabout200˚C
• Mo8onfric8onheatreac8on
4K.N.Palmer,P.S.Tonkin,Combus3onandFlame,1957,14‐18.PhotosbyW.Qualls,h]p://www.caliberdt.com/~bill/tcfire/index.htm
StrikingFlintandSteel
• Strikingflintandsteeltomakesparkisamechanochemicalprocess
• Smallpar8clesofsteelareformed• Oxida8onofironisexothermic• Highsurfaceareaallowsquickreac8on• Mo8onpar8clereac8onheat
5Hildorf,WalterG.;McCollam,C.H.IronAge,1929,124,953‐956.
Dimeriza<onofAnthracene
6V.M.Tapilin,N.N.Bulgakov,A.P.Chupakhin,A.A.Politov,J.Struct.Chem.,2008,49,581‐586.
CalculatedTotalEnergy CalculatedHOMOandLUMO
h!
4+4 cyclization
heat
30 kbar
Pressure Cell
Prepara<onofIRPellets
• KBrorothersaltsmayreactwithanalyteunderhighpressuresusedtopreparepellet.– Ion‐exchange– Complexforma8on• KBrformscomplexeswithsugars,thiourea,succinimide
– Oxida8on‐Reduc8onreac8ons•
7J.Fernández‐Bertran,PureAppl.Chem.,1999,71,581‐586.
FeIII(CN)6-3 + Br- FeII(CN)6
-4 + 1/2 Br2
Tribochemistry:Fric<onalChemistry
• Tribochemistryisthestudyofchemistrycausedbyfric8on,specificallyinlubricants
• Importanttomechanicalengineeringofmovingparts
8S.M.Hsu,J.Zhang,Z.Yin,TribologyLeD.2002,131‐139.
heat
rub+
Fe
O
OH HO+O
O H2O
Addi<vestoLubricants
• Longpolymerstostabilizeviscosity
• Zincdialkyldithiophosphatetopassivateiron
9S.M.Hsu,J.Zhang,Z.Yin,TribologyLeD.2002,131‐139.
ZnS
S
S
SP
OR
ORP
RO
RO
Friction orHeating
High
Low
Low
High
Viscosity Viscosity
TypesofGrindingApparatus
• Mortarandpestle
• Rota8ngballmill
10h]p://www.unitednuclear.com/mills.htm
HighEnergyBallMilling
• Vibra8ngballmill– laboratoryscale– upto100mg
• Planetaryballmill– laboratoryscale– upto100gperbowl
• S8rredballmill– industrialscale– kilograms
11
HowitWorks
• Crushingofpar8clesresultsinlargesurfaceareas
• Mixingofsolidsallowsreac8onatsurfaces
• Thermalequilibriumisbroken– “hotspots”,es8matedat10000K,– Las8ng10‐7seconds
• Collisionsbreakcrystallinematerial
• Highpressures12
J.Fernández‐Bertran,PureAppl.Chem.,1999,71,581‐586.
Transi<onPressureofMinerals
Mineral Geometry Volumeperformulaunit(Å3)
Calcite Trigonal‐Rhombohedral 61
Aragonite Orthorombic 57
• Polymorphicmaterialhavegeometriesthatvarywithpressure
• Phasetransi8onscanbemeasured• Forexample,calciumcarbonate
– Calcite,lowpressurephase– Aragoniteformedabove3000bar
• Aragoniteismetastableatambientpressure
13J.R.Smyth,T.J.Ahrens,Geophys.Res.LeD.,1997,24,1595‐1598.F.Dachille,R.Roy,Nature,1960,186,34,71.
Calcite
Aragonite
HowMuchPressure?
Substance Transi8onTransi8on
Pressure(bar)HighPressure
PhaseObservedaCaCO3 CalcitetoAragonite 3000 yes
PbO2 LeadOxideItoII 10,000 yes
Sb2O3SenarmonitetoValen8nite
10,000 yes
BeF2 15,500 trace
B2O3 ColemanitetoUlexite 18,500 no
BAsO4 30,000 no
14F.Dachille,R.Roy,Nature,1960,186,34,71.
Aoergrindingwithmortarandpestle,orwithvibratoryballmill:
aSamplesanalyzedwithpowerXRDtodeterminephasespresent.(1bar=14.5psi)
OtherFieldsthatuseBallMills
• Materialscience• Powdermanufacturing(e.g.gunpowder)
• Metallurgy
• Inorganicchemistry
15Balema,V.P.,Dennis,K.W.,Pecharsky,V.K.,Chem.Comm.,2000,1665.
3 LiAlH4
Ball Milling, 5 min.
3 mol% TiCl4Room Temp.
Li3AlH6 + 2 Al + 3 H2
100% conversion!G = -6.5 kcal/mol
Outline
• Introduc8ontomechanochemistry• Organicmechanochemicalreac8ons– Oxida8onofalkenes– Amideforma8on– Nitronesynthesis– Asymmetricinduc8on
– Cellulosefunc8onaliza8on• Conclusion
16
Oxida<onwithInorganicSupport
17H.Sohmiya,T.Kimura,P.Bauchat,M.Fujita,T.Ando,Chem.LeD.1991,1391‐1392.
Subtrate Product Yield(%) Substrate Product Yield(%)
65(62a)
82(72a)
74 60
66
Ph
Ph
PhPh
no grindingNoReac8on
PhPh
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Cl
Cl
Ph
Ph
Ph
Ph O
Ph
Ph
Ph
Cl
OH
Ph
Cl
Ph
Cl
Ph
Ph
Cl
Cl
Solid Substrate Product
PhIO, HCl-Silica gel
Grinding in Mortarand Pestle, 5 min.
aSolu8onphase:Solidsubstrate,PHIOandconc.HCls8rredinether,30min.
IO
Ph n
+ n HCl n
ClI
OH
Ph
Pulverize
Step 1:
Step 2:
Ph Ph
Cl I
OH
Ph
Ph Ph
I
OH
Ph
Cl
Ph Ph
I
HOPhCl
Cl Ph Ph
ClCl
Ph Ph
PhPhCl
IOH
Ph
Ph Ph
PhPh O
HCl
Ph Ph
PhPh O
Step 2:
HH2O
PhI
PhI
HCl
ProposedMechanismofAddi<on
18H.Sohmiya,T.Kimura,M.Fujita,T.Ando,Tetrahedron,1998,13737‐13750.
AmideForma<on
• Thetradi8onalwaytomakeanamideistouseanacyla8ngagent,suchasanacidchloride,andreactwithanamine.
19Franzen,Hartwig,BerichtederDeutschenChemischenGesellschaM,1909,2465‐2468.H.Nakatsuji,M.Morimoto,T.Misaki,Y.Tanabe,Tetrahedron,2007,12071‐12080.
Ar
O
Cl Ar
O
NH
Ar'H2N Ar'+ + HCl
Benzene
reflux, 8 h
Ar
O
Cl Ar
O
NH
Ar'H2N Ar'+ + HCl
(1.5 eq)TMEDA(1.5 eq)
CH3CN, 0˚C, 1h
N N
AmidefromAldehyde
• Recently,methodstomakeamidesfromaldehydesandamineswerereported.
20S.Seo,T.J.Marks,Org.LeD.2008,317‐319J.Gao,G.Wang,J.Org.Chem.2008,2955‐2958
R
O
H R
O
NH
R'H2N R'
+benzene, 25 ˚C, 24 h
La[N(TMS)2]3
3 eq.
R
OH+
R
O
H+
H2NR'
OxoneMgSO4
Ball Mill, 30 Hzr.t., 90 min
R
O
NH
R'
Oxidants,Dryingagents,Solvents
Oxidant DryingAgent Solvent Yield(%)
Oxone 61
Oxone 4ÅMS 68
Oxone MgSO4 75
Oxone MgSO4 CH3CN 11
Oxone MgSO4 toluene trace
K2S2O8/CuCl MgSO4 trace
I2 MgSO4 021
J.Gao,G.Wang,J.Org.Chem.2008,2955‐2958
O
H+
NH2Oxidant
Drying agent
Ball Mill, 30 Hzr.t., 90 min
O
NH
O2N O2N
ScopeofReac<on
Product Yield(%) Product Yield(%)
75 38
78 71
65 62
42 65
22
Ar
O
H+
H2NAr'
OxoneMgSO4
Ball Mill, 30 Hzr.t., 90 min
Ar
O
NH
Ar'
O
NH
O2N
O
NH
O
NH
O
NH
O2N
NC
S
O
NH
O2N
O
NH
O
NH
Br
Cl
O
NH
Cl
O2N
Br
NO2
Cl
J.Gao,G.Wang,J.Org.Chem.2008,2955‐2958
MechanismforAmideForma<on• Twopossiblepathwaysareproposed:
23J.Gao,G.Wang,J.Org.Chem.2008,2955‐2958
Ar
O
H
H2NAr'
Ar
O
HNH2
Ar'
protontransfer
Ar
OH
HNH
Ar'
Path A:
Path B:
Ar
H
NAr'
Ar
O
NH
Ar'
Ar
H
NAr'
O
K S
OO
OH
OO
ArH
NAr'
O
+KHSO4
+ H2O
KH
Ar
O
HHN
Ar'
SO
O
O
H
O
O
Oxone
Oxone
Nitrones
• Canbeusedinspin‐labelingstudies– Formstableradicals
• Synthe8cintermediates– Example:[3+2]cycloaddi8onstomakeisoxazoline
24E.Colacino,P.Nun,F.M.Colacino,J.Mar8nez,F.Lamaty,Tetrahedron,2008,5569‐5576.I.S.Young,M.A.Kerr,Angew.Chem.Int.Ed.2003,3023‐3026
NOR1
R2EWG
O
N
EWG
R1
R2
NOR1
R2
+ R• NOR1
R2
R
PreviousSynthesis
25K.Torssell,O.Zeuthen,ActaChem.Scand.Ser.B,1978,118‐124.K.S.Chan,W.‐K.Yeung,R.‐J.Chan,T.‐C.Wang,W.J.Mak,J.Org.Chem.1995,1741‐1747.
• IfR1isabulkygroup,liket‐butyl,thenyieldsarelow.
NOR1
R2
R1NH
OH
R2
O+
R1NH
R2
NOR1
R2
H2O2, Na2WO4 (cat.)
NaHCO3, MgSO4
CH2Cl2, RefluxN2 atmosphere
42-90% yield
MeOH, 0˚C
1.5 eq.
NitroneinaBallMill
R1 R2 Time(h) Yield(%)BallMill
Yield(%)Microwavea
CH3 C6H5 1 82 72
Bn C6H5 1 88 80
C(CH3)3 C6H5 2 100 74
CH3 4‐CN‐C6H4 0.5 93 64
Bn 4‐CN‐C6H4 2 99 n.d.
CH3 4‐I‐C6H4 1 100 n.d.
Bn 4‐I‐C6H4 2 88 65
26
NOR1
R2
R1
NH
OH
R2
O+
Ball Mill, 30 Hz
NaHCO3
E.Colacino,P.Nun,F.M.Colacino,J.Mar8nez,F.Lamaty,Tetrahedron,2008,5569‐5576.
aMicrowaveexperimentdoneat120˚Cfor3hours.
ComparingSolventtoBallMilling
Solvent Condi8on BallMill
40˚C Temperature RoomTemp
CH2Cl2 Solvent None
N2 Atmosphere Air
18–24h Time 0.5‐2h
1:1.5 ReagentRa8o 1:1
Yield:
48% 100%
75% 82%
27E.Colacino,P.Nun,F.M.Colacino,J.Mar8nez,F.Lamaty,Tetrahedron,2008,5569‐5576.
N
O
N
O
AsymmetricInduc<on:OpeningofmesoAnhydrides
MixingCondi8on Temperature Timemolra8o
A:BYield(%) ee(%)
Solvent:toluene roomtemp. 36 1:3 82 79
Solvent:toluene ‐55˚C 96 1:3 96 99
Ballmilling,4Hz roomtemp. 36 1:1 91 61
28
N
OMe
OH
N
Quinidine
C.Bolm,I.Atodiresei,I.Schiffers,Org.Synth.2005,120‐124.B.Rodriguez,T.Rantanen,C.Bolm,Angew.Chem.Int.Ed.2006,6924‐6926.
• Awaytointroducechiralitytoop8callyinac8vespecies.
O
O
O
+
OH
O
OH
O
Oquinidine (1.1eq)
A B
AsymmetricAldolCondensa<on
Product Method Time(h) Yield(%) an'/syn ee(%)
A 5.5 99 89:10 94
B 96 98 87:13 94
A 7 97 93:7 97
B 36 89(10) 91:9 97
A 36 65(25) 66:34 63
B 96 64(26) 71:29 67
A 19 73 ‐ 56
B 36 69 ‐ 5429
B.Rodriguez,T.Rantanen,C.Bolm,Angew.Chem.Int.Ed.2006,6924‐6926.
O
R1 R1 H
O
R2
(s)-proline (10 mol%)
ball mill (A)or stirring (B) R1 R1
O OH
R2+
O OH
NO2
O OH NO2
O OH OMe
O OH
NO2
MetalCatalyzedReac<ons
• Oxida8vecouplingof2‐naphthol
• Heckreac8on
• Palladiumcatalyzedhydrodechlorina8on
B.Rodriguez,A.Bruckmann,T.Rantanen,C.Bolm,Adv.Synth.Catal.2007,349,2213‐233I.Pri‐Bar,B.James,J.Mol.Cat.A:Chemical2007,264,135‐139
30
COOMe
NHBoc
+ INHBoc
COOMe
NaClball mill (13 Hz), 1 h 76%
Pd(OAc)2 (5 mol%)NaHCO3, n-Bu4NClHCOONa (0.2 eq)
2
OH
FeCl3 • 6 H2O
NaClball mill, 1 h
OH
OH
87%
Cl
Cl
Cl
Cl
Cl
Cl
NaOH, ball mill
Pd/C (5 mol%), CaH2
FullereneFunc<onaliza<on
31
N NNR
RN3
ball mill
Si
PhPh
Ph2SiCl2 + Liball mill
H
R
RBr + Mball mill
M=Na,K,Li,Mg
R =
ball mill KCN
H
CN
o-dichlorobenzenesolution
H
CH2CO2Et
Zn + BrCH2CO2Etball mill
G‐W.Wang,EncyclopediaofNanoscienceandNanotechnology,2003,10,1‐9.
Biomass
• Woodiscomprisedofpolymericmaterials– Rigid‐chaincelluloseinamorphousligno‐carbohydratematrix
• Chemicalu8liza8onofbiomassishamperedbylowsolubilityinsolvents
32I.V.Mikushina,I.B.Troitskaya,A.V.Dushkin,Y.A.Ol’khov,N.G.Bazarnova,Chem.forSust.Devel.2003,363‐370.h]p://www.fotosearch.com/photos‐images/wood.html
O
H
H
OH
H
H
OH
H
O
HO
O
H
H
OH
H
H
OH
H
O
HO
O
H
H
OH
H
H
OH
H
O
HO
O
H
H
OH
H
H
OH
H
HO
HO
O
H
OH
H
OH
H
H
OH
H
O
HO
O
H
H
OH
H
H
OH
H
O
HO
BallMillingofWood
• Testsdoneonsawdust• Par8clesizedecreasesfrom400µmto3‐16µm
• Specificsurfaceareaincreases(includesporesandchannelsinpar8cles)
• Fibrousstructureislostquickly• Cellulosepolymerlengthisshortened• Crystallinityofcellulosedecreasedbymilling,increasesifheated
33I.V.Mikushina,I.B.Troitskaya,A.V.Dushkin,Y.A.Ol’khov,N.G.Bazarnova,Chem.forSust.Devel.2003,363‐370.
ComparisonofMillingTypes
MillType Time(min)SpecificSurface
(m2/g)CrystallinityDegree(%)
Ini8alWood 0 0.6 81
Rota8ng 315 3.0 63
Planetary 2 2.2 100
VibratoryCentrifugal(balls)
15 2.5 100
VibratoryCentrifugal(cylinders)
15 1.1 63
34I.V.Mikushina,I.B.Troitskaya,A.V.Dushkin,Y.A.Ol’khov,N.G.Bazarnova,Chem.forSust.Devel.2003,363‐370.
CelluloseAcetate
• Celluloseacetateisusedinfilmsandtex8les• Tradi8onally,celluloseacetateismadewithsulfuricacidascatalyst– Expensivesolvent– Wastesulfuricacidisgenerated
35L.Yan,W.Li,Z.Qi,S.Liu,J.ofPolymerRes.2006,375‐378.
Ball Milling, 5 Hz
Acetic Anhydride
SO42-/ZrO2 (cat.)
Cellulose Cellulose Acetate + Acetic Acid
LiCl/N,N-dimethylacetamide
Acetic AnhydrideH2SO4 (cat.)
Cellulose Cellulose Acetate + Acetic Acid
SynthesisofCelluloseAcetate
36L.Yan,W.Li,Z.Qi,S.Liu,J.ofPolymerRes.2006,375‐378.
MillingTime(h) 0 1.0 2.5 5.0 7.5
DegreeofSubs8tu8on
0 0.43 1.19 1.65 1.80
DegreeofPolymeriza8on
420 403 397 355 324 0
50
100
150
200
250
300
350
400
450
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
0 2 4 6 8
DegreeofPolym
eriza<
on
DegreeofSub
s<tu<on
Time(h)
DegreeofSubs8tu8on DegreeofPolymeriza8on
OH
OHOH
OH
Ball Milling Ball Milling
Acetic Anhydride
SO42-/ZrO2 (cat.)
O
O
CH3
O
ORO
OR
R = H, COCH3
OH
HO
HO
HO
SpinLabelingStudy
• 1‐oxyl‐3‐imidazoline‐3‐oxideradicalsstudiedbyEPR
• Radicalsareevenlydistributedandisolated
• Tworadicalsseen:– looselybound
adsorbed– 8ghtlybound
covalentlybonded• Approximately1
radicalpermonomer37
A.V.Dushkin,I.B.Troitskaya,V.V.Boldyrev,I.A.Grigor’ev,Russ.Chem.Bull.Int.Ed,2005,1155‐1159.
N
N
O
O
N
N
O
OO
OH
N
N
O
OBr
Cellulose
Ball Milling
Cellulose
Ball Milling
Cellulose
Ball MillingNaOH
N
N
O
OO
O
N
N
O
O
O
N
N
O
OH O
FutureResearchPossibili<es
• Furtherelucida8onofmechanochemicalmechanism– comparereac8onselec8viestotemperaturestudiestofind“effec8vetemperature”
• Extendmethodtoothersynthe8creac8ons– Seemstoworkwellforcouplingtypereac8ons
• Con8nuedfocusonbiomassu8liza8on– Solidmaterialsthatarehardtoworkwithchemicallyduetotheirinsolubilityinsolvents
38
Conclusion
• Mechanochemistryoffersasimple,efficient,environmentallyfriendlysynthe8cmethod.
• Manyorganicreac8onsareamenabletouseinballmills.
• Ofspecialinterestarereac8onsthatusesolidreagents,par8cularlyreagentsnotreadilysolubleinorganicsolvents.
39
Acknowledgements
• Dr.NedJackson• Dr.BabakBorhan
• Karrie,Partha,Misha,Cur8s
• Mike,Sarah,Gina,Tom
• Cora,Kamina,Raelani,Bill
40
ThankYouHaveagreatspringbreak!
"PiledHigherandDeeper"byJorgeChamwww.phdcomics.com
HN
OHR1
R2
R1
NH2
OH
R2
O
R1
NH
OH
NaHCO3
O
p.t.N
OR1
R2 O
H
H
NOR1
R2 O
H
H
NOR1
R2
O R1
HR2
OH2
R1 O
HR2
OH2
NOR1
R2
NOR1
R2
Cl
MechanismforNitroneForma<on
42
MechanismofLanthanideMediatedAmida<on
43
NHR1R2
NH(SiMe3)2
La[N(SiMe3)2]3
LaN
O
HR La
N
O HR
O
H R La
N
O R
O
H RH
RHO
O
HR
O
H R
LaN