Mechanochemistry - Department of Chemistry

Mechanochemistry - Department of Chemistry

Mechanochemistry:
Solvent‐Free
Organic
Reac8ons
in
the
Solid
Phase
Peter
M.
Lambert
March
4th,
2009
Department
of
Chemistry
Michigan
State
University
1
Outline
• Introduc8on
to
mechanochemistry
• Organic
mechanochemical
reac8ons
– Oxida8on
of
alkenes
– Amide
forma8on
– Nitrone
synthesis
– Asymmetric
induc8on
– Cellulose
func8onaliza8on
• Conclusion
2
Types
of
Chemistry
• Thermochemistry
– heat
ac8va8on
• Photochemistry
– light
ac8va8on
• Electrochemistry
– electrical
ac8va8on
• Mechanochemistry
– physical
ac8va8on
J.
Fernández‐Bertran,
Pure
Appl.
Chem.,
1999,
71,
581‐586.
3
Combus<on
• Rubbing
s8cks
together
to
make
fire
• Combus8on
starts
about
200˚C
• Mo8on

fric8on

heat

reac8on
K.
N.
Palmer,
P.
S.
Tonkin,
Combus3on
and
Flame,
1957,
14‐18.
Photos
by
W.
Qualls,
h]p://www.caliberdt.com/~bill/tcfire/index.htm
4
Striking
Flint
and
Steel
• Striking
flint
and
steel
to
make
spark
is
a
mechanochemical
process
• Small
par8cles
of
steel
are
formed
• Oxida8on
of
iron
is
exothermic
• High
surface
area
allows
quick
reac8on
• Mo8on

par8cle

reac8on

heat
Hildorf,
Walter
G.;
McCollam,
C.
H.
Iron
Age,
1929,
124,
953‐956.
5
Dimeriza<on
of
Anthracene
h!
4+4 cyclization
heat
30 kbar
Calculated
Total
Energy
Pressure Cell
Calculated
HOMO
and
LUMO
6
V.
M.
Tapilin,
N.
N.
Bulgakov,
A.
P.
Chupakhin,
A.
A.
Politov,
J.
Struct.
Chem.,
2008,
49,
581‐586.
Prepara<on
of
IR
Pellets
• KBr
or
other
salts
may
react
with
analyte
under
high
pressures
used
to
prepare
pellet.
– Ion‐exchange
– Complex
forma8on
• KBr
forms
complexes
with
sugars,
thiourea,
succinimide
– Oxida8on‐Reduc8on
reac8ons
• FeIII(CN)6-3 + Br-
J.
Fernández‐Bertran,
Pure
Appl.
Chem.,
1999,
71,
581‐586.
FeII(CN)6-4 + 1/2 Br2
7
Tribochemistry:
Fric<onal
Chemistry
• Tribochemistry
is
the
study
of
chemistry
caused
by
fric8on,
specifically
in
lubricants
• Important
to
mechanical
engineering
of
moving
parts
rub
+
Fe
O
H2O
O
OH
+
HO
S.M.
Hsu,
J.
Zhang,
Z.
Yin,
Tribology
LeD.
2002,
131‐139.
heat
O
8
Addi<ves
to
Lubricants
• Long
polymers
to
stabilize
viscosity
Viscosity
Viscosity
High
Low
Friction or
Heating
High
Low
• Zinc
dialkyl
dithiophosphate
to
passivate
iron
RO
S
P
RO
S.M.
Hsu,
J.
Zhang,
Z.
Yin,
Tribology
LeD.
2002,
131‐139.
S
S
OR
P
Zn
S
OR
9
Types
of
Grinding
Apparatus
• Mortar
and
pestle
• Rota8ng
ball
mill
10
h]p://www.unitednuclear.com/mills.htm
High
Energy
Ball
Milling
• Vibra8ng
ball
mill
– laboratory
scale
– up
to
100
mg
• Planetary
ball
mill
– laboratory
scale
– up
to
100
g
per
bowl
• S8rred
ball
mill
– industrial
scale
– kilograms
11
How
it
Works
• Crushing
of
par8cles
results
in
large
surface
areas
• Mixing
of
solids
allows
reac8on
at
surfaces
• Thermal
equilibrium
is
broken
– “hot
spots”,
es8mated
at
10000
K,
– Las8ng
10‐7
seconds
• Collisions
break
crystalline
material
• High
pressures
J.
Fernández‐Bertran,
Pure
Appl.
Chem.,
1999,
71,
581‐586.
12
Transi<on
Pressure
of
Minerals
• Polymorphic
material
have
geometries
that
vary
with
pressure
• Phase
transi8ons
can
be
measured
• For
example,
calcium
carbonate
Calcite
– Calcite,
low
pressure
phase
– Aragonite
formed
above
3000
bar
• Aragonite
is
metastable
at
ambient
pressure
Mineral
Calcite
Aragonite
Aragonite
Volume
per
formula
unit
(Å3)
Trigonal‐
Rhombohedral
61
Geometry
Orthorombic
J.
R.
Smyth,
T.
J.
Ahrens,
Geophys.
Res.
LeD.,
1997,
24,
1595‐1598.
F.
Dachille,
R.
Roy,
Nature,
1960,
186,
34,71.
57
13
How
Much
Pressure?
Aoer
grinding
with
mortar
and
pestle,
or
with
vibratory
ball
mill:
Transi8on
High
Pressure
Pressure
(bar)
Phase
Observeda
Substance
Transi8on
CaCO3
Calcite
to
Aragonite
3000
yes
PbO2
Lead
Oxide
I
to
II
10,000
yes
Sb2O3
Senarmonite
to
Valen8nite
10,000
yes
15,500
trace
18,500
no
30,000
no
BeF2
B2O3
Colemanite
to
Ulexite
BAsO4
a
Samples
analyzed
with
power
XRD
to
determine
phases
present.
(1
bar=14.5
psi)
F.
Dachille,
R.
Roy,
Nature,
1960,
186,
34,71.
14
Other
Fields
that
use
Ball
Mills
• Material
science
• Powder
manufacturing
(e.g.
gunpowder)
• Metallurgy
• Inorganic
chemistry
Ball Milling, 5 min.
3 LiAlH4
Li3AlH6 + 2 Al + 3 H2
3 mol% TiCl4
Room Temp.
Balema,
V.P.,
Dennis,
K.W.,
Pecharsky,
V.K.,
Chem.
Comm.,
2000,
1665.
100% conversion
!G = -6.5 kcal/mol
15
Outline
• Introduc8on
to
mechanochemistry
• Organic
mechanochemical
reac8ons
– Oxida8on
of
alkenes
– Amide
forma8on
– Nitrone
synthesis
– Asymmetric
induc8on
– Cellulose
func8onaliza8on
• Conclusion
16
Oxida<on
with
Inorganic
Support
PhIO, HCl-Silica gel
Solid Substrate
Product
Grinding in Mortar
and Pestle, 5 min.
Subtrate
Ph
Ph
Product
Ph
Cl
Ph
Ph
Cl
Cl
Cl
Ph
Ph
Cl
Ph
OH
Ph
Ph
Ph
Ph
Yield
(%)
Ph
Ph
65
(62a)
Substrate
Product
Ph
Ph
Ph
Ph
Ph
Ph
O
Cl
Yield
(%)
Ph
Ph
74
82
(72a)
60
Cl
66
Ph
Ph
no grinding
No
Reac8on
a
Solu8on
phase:
Solid
substrate,
PHIO
and
conc.
HCl
s8rred
in
ether,
30
min.
H.
Sohmiya,
T.
Kimura,
P.
Bauchat,
M.
Fujita,
T.
Ando,
Chem.
LeD.
1991,
1391‐1392.
17
Proposed
Mechanism
of
Addi<on
I
Step 1:
O
Cl
Pulverize
n
+ n HCl
Ph
OH
I
Ph
n
Step 2:
OH
Cl
I
OH
Cl
I
Ph
Ph
Ph
Ph
HO
Cl
Ph
Ph
Ph
Step 2:
Cl
OH
I
Ph
Ph
Ph
Ph
Cl
H
Ph
O
H2O
H
I
Ph
Ph
Cl
Cl
Cl
Ph
Ph
PhI
HCl
Ph
Ph
O
Ph
Ph
PhI
Ph
H.
Sohmiya,
T.
Kimura,
M.
Fujita,
T.
Ando,
Tetrahedron,
1998,
13737‐13750.
Ph
Ph
Ph
18
Amide
Forma<on
• The
tradi8onal
way
to
make
an
amide
is
to
use
an
acyla8ng
agent,
such
as
an
acid
chloride,
and
react
with
an
amine.
O
+
Ar
Cl
H2N
+
Ar
Ar'
reflux, 8 h
N
O
Cl
H2N
Ar'
O
Benzene
Ar
N
(1.5 eq)
TMEDA(1.5 eq)
CH3CN, 0˚C, 1h
Franzen,
Hartwig,
Berichte
der
Deutschen
Chemischen
GesellschaM,
1909,
2465‐2468.
H.
Nakatsuji,
M.
Morimoto,
T.
Misaki,
Y.
Tanabe,
Tetrahedron,
2007,
12071‐12080.
N
H
Ar'
+ HCl
O
Ar
N
H
Ar'
+ HCl
19
Amide
from
Aldehyde
• Recently,
methods
to
make
amides
from
aldehydes
and
amines
were
reported.
O
+
R
H
H2N
O
La[N(TMS)2]3
R'
benzene, 25 ˚C, 24 h
R
3 eq.
O
+
R
H
S.
Seo,
T.
J.
Marks,
Org.
LeD.
2008,
317‐319
J.
Gao,
G.
Wang,
J.
Org.
Chem.
2008,
2955‐2958
H2N
R'
OH
N
H
Oxone
MgSO4
Ball Mill, 30 Hz
r.t., 90 min
R'
+
R
O
R
N
H
R'
20
Oxidants,
Drying
agents,
Solvents
NH2
O
Oxidant
Drying agent
+
O 2N
H
O
O 2N
Ball Mill, 30 Hz
r.t., 90 min
Oxidant
Drying
Agent
Solvent
Oxone
N
H
Yield
(%)
61
Oxone
4
Å
MS
68
Oxone
MgSO4
75
Oxone
MgSO4
CH3CN
11
Oxone
MgSO4
toluene
trace
K2S2O8/CuCl
MgSO4
trace
I2
MgSO4
0
J.
Gao,
G.
Wang,
J.
Org.
Chem.
2008,
2955‐2958
21
Scope
of
Reac<on
O
+
Ar
H
Product
O
O2N
N
H
H2N
Ar'
Oxone
MgSO4
O
Ball Mill, 30 Hz
r.t., 90 min
Yield(%)
Ar
Product
NO2
75
N
H
78
O
N
H
65
O 2N
38
Br
Cl
S
N
H
J.
Gao,
G.
Wang,
J.
Org.
Chem.
2008,
2955‐2958
Cl
62
N
H
Br
O
42
71
N
H
O2N
NC
O
Yield(%)
N
H
O
O2N
Ar'
O
O
O
N
H
N
H
65
Cl
22
Mechanism
for
Amide
Forma<on
• Two
possible
pathways
are
proposed:
O
Ar
O
H
H2N
Ar
Ar'
Ar'
Ar
N
H H
Path B:
Ar'
O
H
Ar
Path A:
N
Ar'
HN
H
O
O
H
Ar
K
H
S
O
O
O
Oxone
Ar'
H
O
O
K
N
H H2
OH
proton
transfer
O
S
O
O
Oxone
O
N
Ar
H
O
Ar'
O
Ar
J.
Gao,
G.
Wang,
J.
Org.
Chem.
2008,
2955‐2958
H
Ar
N
Ar'
N
H
+ H2O
+KHSO4
Ar'
23
Nitrones
• Can
be
used
in
spin‐labeling
studies
– Form
stable
radicals
R1
• Synthe8c
intermediates
N
R1
O
+ R•
N
O
R
R2
R2
– Example:
[3+2]
cycloaddi8ons
to
make
isoxazoline
R1
N
R1 N
O
R2
EWG
E.
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
R2
O
EWG
24
Previous
Synthesis
R1
H2O2, Na2WO4 (cat.)
NH
R1
N
O
MeOH, 0˚C
R2
R2
R1
N
H
OH
O
NaHCO3, MgSO4
R1
+
R2
1.5 eq.
CH2Cl2, Reflux
N2 atmosphere
N
O
42-90% yield
R2
• If
R1
is
a
bulky
group,
like
t‐butyl,
then
yields
are
low.
K.
Torssell,
O.
Zeuthen,
Acta
Chem.
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.
25
Nitrone
in
a
Ball
Mill
R1
N
H
OH
R1
Ball Mill, 30 Hz
O
+
NaHCO3
R2
N
O
R2
R1
R2
Time
(h)
Yield
(%)
Ball
Mill
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
a
Microwave
experiment
done
at
120
˚C
for
3
hours.
E.
Colacino,
P.
Nun,
F.
M.
Colacino,
J.
Mar8nez,
F.
Lamaty,
Tetrahedron,
2008,
5569‐5576.
26
Comparing
Solvent
to
Ball
Milling
Solvent
Condi8on
Ball
Mill
40˚C
Temperature
Room
Temp
CH2Cl2
Solvent
None
N2
Atmosphere
Air
18
–
24
h
Time
0.5
‐
2
h
1
:
1.5
Reagent
Ra8o
1
:
1
Yield:
48
%
75
%
100
%
N
O
N
O
E.
Colacino,
P.
Nun,
F.
M.
Colacino,
J.
Mar8nez,
F.
Lamaty,
Tetrahedron,
2008,
5569‐5576.
82
%
27
Asymmetric
Induc<on:
Opening
of
meso
Anhydrides
• A
way
to
introduce
chirality
to
op8cally
inac8ve
species.
OMe
OH
O
O
A
+
O
O
quinidine
(1.1eq)
OH
N
O
OH
N
Quinidine
O
B
Mixing
Condi8on
Temperature
Time
mol
ra8o
A:B
Yield
(%)
ee
(%)
Solvent:
toluene
room
temp.
36
1:3
82
79
Solvent:
toluene
‐55
˚C
96
1:3
96
99
Ball
milling,
4
Hz
room
temp.
36
1:1
91
61
C.
Bolm,
I.
Atodiresei,
I.
Schiffers,
Org.
Synth.
2005,
120‐124.
B.
Rodriguez,
T.
Rantanen,
C.
Bolm,
Angew.
Chem.
Int.
Ed.
2006,
6924‐6926.
28
Asymmetric
Aldol
Condensa<on
O
+
R1
R1
Product
O
OH
NO2
O
O
O
OH
OH
NO2
OMe
OH
NO2
(s)-proline (10 mol%)
O
H
ball mill (A)
or stirring (B)
R2
O
OH
R2
R1
R1
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
‐
54
B.
Rodriguez,
T.
Rantanen,
C.
Bolm,
Angew.
Chem.
Int.
Ed.
2006,
6924‐6926.
29
Metal
Catalyzed
Reac<ons
• Oxida8ve
coupling
of
2‐naphthol
FeCl3 • 6 H2O
2
NaCl
ball mill, 1 h
OH
OH
OH
87%
• Heck
reac8on
COOMe
+
I
NHBoc
Pd(OAc)2 (5 mol%)
NaHCO3, n-Bu4NCl
HCOONa (0.2 eq)
NaCl
ball mill (13 Hz), 1 h
COOMe
NHBoc
76%
• Palladium
catalyzed
hydrodechlorina8on
Cl
Cl
Cl
Cl
Cl
Pd/C (5 mol%), CaH2
NaOH, ball mill
Cl
B.
Rodriguez,
A.
Bruckmann,
T.
Rantanen,
C.
Bolm,
Adv.
Synth.
Catal.
2007,
349,
2213‐233
I.
Pri‐Bar,
B.
James,
J.
Mol.
Cat.
A:
Chemical
2007,
264,
135‐139
30
Fullerene
Func<onaliza<on
H
H
CN
CH2CO2Et
o-dichlorobenzene
solution
ball mill
KCN
Zn + BrCH2CO2Et
ball mill
R N N N
RN3
ball mill
Ph2SiCl2 + Li
ball mill
RBr + M
ball mill
M=Na,K,Li,Mg
R=
Ph Ph
Si
H
R
G‐W.
Wang,
Encyclopedia
of
Nanoscience
and
Nanotechnology,
2003,
10,
1‐9.
31
HO
Biomass
• Wood
is
comprised
of
polymeric
materials
– Rigid‐chain
cellulose
in
amorphous
ligno‐
carbohydrate
matrix
• Chemical
u8liza8on
of
biomass
is
hampered
by
low
solubility
in
solvents
H
OH
O
H
H
HO
H
H
OH
O
O
H
HO
H
H
OH
H
H
OH
O
H
OH
O
H
H
HO
H
H
OH
O
H
OH
O
H
H
HO
H
H
OH
O
H
OH
O
H
I.
V.
Mikushina,
I.
B.
Troitskaya,
A.
V.
Dushkin,
Y.
A.
Ol’khov,
N.
G.
Bazarnova,
Chem.
for
Sust.
Devel.
2003,
363‐370.
h]p://www.fotosearch.com/photos‐images/wood.html
H
HO
H
O
O
H
H
OH
32
H
OH
Ball
Milling
of
Wood
• Tests
done
on
sawdust
• Par8cle
size
decreases
from
400
µm
to
3‐16
µm
• Specific
surface
area
increases
(includes
pores
and
channels
in
par8cles)
• Fibrous
structure
is
lost
quickly
• Cellulose
polymer
length
is
shortened
• Crystallinity
of
cellulose
decreased
by
milling,
increases
if
heated
I.
V.
Mikushina,
I.
B.
Troitskaya,
A.
V.
Dushkin,
Y.
A.
Ol’khov,
N.
G.
Bazarnova,
Chem.
for
Sust.
Devel.
2003,
363‐370.
33
Comparison
of
Milling
Types
Mill
Type
Time
(min)
Specific
Surface
(m2/g)
Crystallinity
Degree
(%)
Ini8al
Wood
0
0.6
81
Rota8ng
315
3.0
63
Planetary
2
2.2
100
Vibratory
Centrifugal
(balls)
15
2.5
100
Vibratory
Centrifugal
(cylinders)
15
1.1
63
I.
V.
Mikushina,
I.
B.
Troitskaya,
A.
V.
Dushkin,
Y.
A.
Ol’khov,
N.
G.
Bazarnova,
Chem.
for
Sust.
Devel.
2003,
363‐370.
34
Cellulose
Acetate
• Cellulose
acetate
is
used
in
films
and
tex8les
• Tradi8onally,
cellulose
acetate
is
made
with
sulfuric
acid
as
catalyst
– Expensive
solvent
– Waste
sulfuric
acid
is
generated
Cellulose
LiCl/N,N-dimethylacetamide
Cellulose Acetate + Acetic Acid
Acetic Anhydride
H2SO4 (cat.)
Cellulose
Ball Milling, 5 Hz
Cellulose Acetate + Acetic Acid
Acetic Anhydride
SO42-/ZrO2 (cat.)
L.
Yan,
W.
Li,
Z.
Qi,
S.
Liu,
J.
of
Polymer
Res.
2006,
375‐378.
35
Synthesis
of
Cellulose
Acetate
OH
O
H
O
O
H
H
O
Ball Milling
OH
O
OH
O
Ball Milling
O
Acetic Anhydride
SO42-/ZrO2 (cat.)
RO
R = H, COCH3
Degree
of
Subs8tu8on
Degree
of
Polymeriza8on
0
420
1.0
2.5
5.0
7.5
0.43
1.19
1.65
1.80
403
397
355
324
Degree
of
Subs<tu<on
2
0
O
OR
OH
Milling
Time
(h)
CH3
450
1.8
400
1.6
350
1.4
300
1.2
250
1
200
0.8
150
0.6
0.4
100
0.2
50
0
Degree
of
Polymeriza<on
H
0
0
2
4
6
8
Time
(h)
Degree
of
Subs8tu8on
L.
Yan,
W.
Li,
Z.
Qi,
S.
Liu,
J.
of
Polymer
Res.
2006,
375‐378.
Degree
of
Polymeriza8on
36
Spin
Labeling
Study
O
N
Cellulose
Ball Milling
N
O
O
N
O
N
O
N
O
OH
Cellulose
O
N
O
O
Ball Milling
N
O
O
N
O
N
H O
N
O
Br
Cellulose
Ball Milling
NaOH
O
N
N
O
O
• 1‐oxyl‐3‐
imidazoline‐3‐oxide
radicals
studied
by
EPR
• Radicals
are
evenly
distributed
and
isolated
• Two
radicals
seen:
– loosely
bound
adsorbed
– 8ghtly
bound
covalently
bonded
• Approximately
1
radical
per
monomer
A.
V.
Dushkin,
I.
B.
Troitskaya,
V.
V.
Boldyrev,
I.
A.
Grigor’ev,
Russ.
Chem.
Bull.
Int.
Ed,
2005,
1155‐1159.
37
Future
Research
Possibili<es
• Further
elucida8on
of
mechanochemical
mechanism
– compare
reac8on
selec8vies
to
temperature
studies
to
find
“effec8ve
temperature”
• Extend
method
to
other
synthe8c
reac8ons
– Seems
to
work
well
for
coupling
type
reac8ons
• Con8nued
focus
on
biomass
u8liza8on
– Solid
materials
that
are
hard
to
work
with
chemically
due
to
their
insolubility
in
solvents
38
Conclusion
• Mechanochemistry
offers
a
simple,
efficient,
environmentally
friendly
synthe8c
method.
• Many
organic
reac8ons
are
amenable
to
use
in
ball
mills.
• Of
special
interest
are
reac8ons
that
use
solid
reagents,
par8cularly
reagents
not
readily
soluble
in
organic
solvents.
39
Acknowledgements
• Dr.
Ned
Jackson
• Dr.
Babak
Borhan
• Karrie,
Partha,
Misha,
Cur8s
• Mike,
Sarah,
Gina,
Tom
• Cora,
Kamina,
Raelani,
Bill
40
Thank
You
Have
a
great
spring
break!
"Piled
Higher
and
Deeper"
by
Jorge
Cham
www.phdcomics.com
Mechanism
for
Nitrone
Forma<on
R1
N
H2
OH
R1
NaHCO3
N
H
OH
R1 H OH
N
p.t.
R1
N
R2
O
R2
O
R2
H
R1
O
H
O
Cl
R2
O
H
R2
H
R1
N
O
R1
O
OH2
OH2
R2
O
H
H
R1
R2
N
O
R1
N
O
R2
R1
N
O
R2
42
Mechanism
of
Lanthanide
Mediated
Amida<on
R
HO
La[N(SiMe3)2]3
NHR1R2
NH(SiMe3)2
La
H
N
R
O
O
H
H
H
R
La
R
O
O
La
O
R
N
H
H
La
R
H
R
O
N
O
R
N
43