Oxidative Addition

&
Reductive Elimination

Mechanisms of Organotransition Metal Reactions

ClassificationM -of
OM Reactions
C
A.

Rearrangements, Isomerizations
M - L'

M - L
B.

Ligand Insertion Reactions

X
M

C.

Oxidative Addition Reductive Elimination

Mn+

D.

M(n+x)+

Reactivity changes on the Ligand

M

L'

Oxidative Addition & Reductive Elimination

X

M
L

Y
L
or

XY
L

L
M
L

Y
d8 metal

Coordination Sat.
+

M
L

L
L

Y-

XY
L

d8 Sat.

L
X

M
L

Y
L

If we consider
X and Y to be
More enegative than
M (X- and Y-)

Polar addenda

I group
1. HX

ArSO 2cl

2. X2
3. RX

halogens
RCOX

Sncl4
Hgcl 2

all add to Ir(I) as if they are A+, B all of them will add to olefins.

II Group
II group

O2, S2
RN3
acetylenes, S = C = S
ROCN3 RCON3
o
Ir

one bond
retained.

III Group
No multiple bonds / Not polar
III group

agostic
H2

Ar - H
C-H

Si - H
R - SH

Polarity Small.
Splitting of H - H bond.

Mechanistic Studies with Group I

CH3
OC

L
M

M = Ir(I)
Y = halogen
L = PPh3

OC
+

CH3 - X

Kinetics

M
L

Y
X

Ist order kinetics in Ir(I)

I st order kinetics in CH3X

Rate increases in polar

solvent
S # = -43.1ev
Relative Rates
X = I > Br > Cl
Y = F > Cl > Br > I
L = PEt3 > PPh3 > (PhO)3P

CH3
OC

+ CH - X
3

M
L

OC

Y
X
dx2-y2

Simple SN2 displacement of X by Ir(I)

H
Ir

dz2

C
H

dxy

H
Stereochemistry at carbon ?
dxz, dyz

CH3
OC

L
+

M
L

OC

CH3 L

OC

CH3

MeOH

M
L

X-

OC

OC

CH3
OC

+ CH 3

M
L

OC

L
M

+ CH - X
3

CH3

XY

MeOH

OC

CH3

M
L

M
Y

O C

CH3

CH3
OC

L
Y

+ CH 3

M
L

OC

Y
X

Relative Rates
X = I > Br > Cl
L = PEt3 > PPh3 > (PhO)3P
Y = F > Cl > Br > I

PPhMe2 > PEt3

CH3
OC

OC

+ CH 3

Y
X

dx2-y2

dz2
dxy

Simple SN2 displacement of X by Ir(I)

H
Ir

C
H

dxz, dyz

H
Stereochemistry at carbon ?

To determine stereochemistry
R

R
C

H
D

or

R2
H

Reactions were done with Ir(I) (Vaska's complex)

Observe complete loss in the

chirality at carbon*

To determine stereochemistry
R

R
C

H
D

or

??
Initiation by AIBN

R2
H

Inhibition by Duroquinone
Racemisation of chiral substrates

Reactions were done with Ir(I) (Vaska's complex)

Observe complete loss in the

chirality at carbon*

The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

Polar SN2 vs Radical Paths

CH2

K1 -1.3x108Sec-'
CH2
Radical clock

Fe
OC

Na

Fe
OC

OC

X=I
= Br
Failure of ESR
J.Am. chem. Soc.

99,

250,

1977

OC

Fe

+
OC

OC

70

30

>97

II Group
O2, S2
RN3
acetylenes, S = C = S
RCON3
ROCN
3
o
Ir

one bond
retained.

The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.

Vaskas complex reacts with dioxygen 1961

PPh3

PPh3
Cl

Ir
PPh3

R-CC-R
CO

Cl

Ir
CO
PPh3

Vaskas complex reacts with acetylenes! 1961

R
R

Oxidative Addition with C-C

Coupling

R
R

R
CpCoL2 + 3 RC

Cp =

CR
R

R
R

R
R

R
CpCo
-2L

CpCo
R

CpCoL2 + 2 RC CR

R
R

2L

R
R

+ Cp Co

When L = PPh3

Co

PPhR
3

CpCo
R

1. Intermediate isolated and characterised .

2. Shown to be catalytically active.
3. Kinetic analysis shows loss of PPh3 is Istep.
4. Replace PPh3 with PMe3 competely stops reaction.

Two possibilities exist

' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

Two possibilities exist

' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

Oxidative Addition
Coordination number increases by 2
Oxidation state increases by 2!
Oxidation state can increase by 2 and the
coordination number can increase by ONE!
Oxidation state can also increase by one!
And no change in coordination number need
be there.
Remember it is a formal oxidation state!

Oxida&ve)Addi&on))
&)
Reduc&ve)Elimina&on)
Part)II)

Mechanisms of Organotransition Metal Reactions

M - C
Classica&on)of)OM)Reac&ons)
A.

Rearrangements, Isomerizations
M - L'

M - L
B.

Ligand Insertion Reactions

X
M

C.

Oxidative Addition Reductive Elimination

Mn+

D.

M(n+x)+

Reactivity changes on the Ligand

M

L'

Group)I)

Group)II)

Brief)comment)on)stability)of)Ox)
species!) O
Ph 3P
OC

CH3

Cl

Ir

PPh3

Ph 3P

Ir

OC
Cl

H3C
C
C
Ph 3P

Ir

OC
Cl

PPh3

CH3

PPh3

Oxida&ve)Addi&on)with)CEC)
Coupling)
)

HC

Cp

Cp

CH

CH.
Co

Co

CH.
HC

CH

Cp
Co

R
R

R
CpCo
-2L

CpCo
R

CpCoL2 + 2 RC CR

R
R

2L

R
R

+ Cp Co

When L = PPh3

Co

PPhR
3

CpCo
R

1. Intermediate isolated and characterised .

2. Shown to be catalytically active.
3. Kinetic analysis shows loss of PPh3 is Istep.
4. Replace PPh3 with PMe3 competely stops reaction.

Two possibilities
exist
C_C)Coupling))followed)by)Inser&on)Reac&on)
' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

Two possibilities
exist
C_C)Coupling))followed)by)Inser&on)Reac&on)
' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

Two possibilities
exist
C_C)Coupling))followed)by)Inser&on)Reac&on)
' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

C_C)coupling)followed)by)a)Deils)Alder)Reac&on)

Two possibilities exist

' CpCo'

CpCo

R C

+
R

Cp

N D.A

Co

CpCo

R
R

R
R
Cp Co +
N

C_C)coupling)followed)by)a)Deils)Alder)Reac&on)
)with)a)nitrile.)
Cp

Cp

Co

Co
RC
N

HC

CH

Cp

Co

Co

Cp
R

RC
N

Cp

Cp

PPh3
Co

Co

Cp

Cp
Co

Co

Cp
Co

Cp
Cp

Co

Co

Cp
Cp
Co

Co

Group)III)

III)Group)
No)mul&ple)bonds)/)Not)polar)
III group

agostic
H2

Ar - H
C-H

Si - H
R - SH

Polarity Small.
Splitting of H - H bond.

Formal)Oxida&on!)
Mn2(CO)10))))can)react)with)hydrogen!)

Mn2(CO)10

H2

HMn(CO)5

Formal)Oxida&on!)

Mn2(CO)10

+ Na/Hg

NaMn(CO)5 + HOAc

NaMn(CO)5

HMn(CO)5 + NaOAc

Formal)Oxida&on)State)Change!)
PPh3

PPh3
Cl

Ir

H2
CO

PPh3

Vaskas))complex)reacts)with)dihydrogen)1961)
)

H
Cl

Ir
CO
PPh3

PMe2

PMe2

Ru
PMe2

PMe2
H

PMe2

Discovered)in)1965)by)ChaY))

PMe2
PMe2
Ru

PMe2

CEH)ac&va&on!)
-H2

Ir

h)

Me3P

Ir
Me3P

H3C

CH3

H3C

H3C
CH3

CH3
Ir

)
Bergman)1982)

Me3P
H

CH3

CEH)ac&va&on!)
h)
C6F12
Ir
CO

CH4
CO

Graham)1983)
)
Bergman)1982)
Whitesides)1986)

Ir
CO

CH3
H

Oxida&ve)Addi&on)of)Neutral)Groups)
Important)criteria)is)thermodynamics)
Oxida&ve)addi&on)of)dihydrogen)is)
exothermic)with)late)transi&on)metals..)
But)MEC)and)MEH)bond)energies)do)not)
compensate)for)CEH)when)M)is)3d)and)so)they)
are)o^en)endothermic.))
So)the)reverse)reac&on)is)more)favorable)

Oxida&ve)Addi&on)
Coordina&on)number)increases)by)2)
Oxida&on)state)increases)by)2!)
Oxida&on)state)can)increase)by)2)and)the)
coordina&on)number)can)increase)by)ONE!)
Oxida&on)state)can)also)increase)by)one!)And)
no)change)in)coordina&on)number)need)be)
there.))
Remember)it)is)a)formal)oxida&on)state!)

Reduc&ve(Elimina&on(
Oxida&ve(addi&on(and(Reduc&ve(
Elimina&on((

Thermodynamics(of(OA(
Group(I(
Two(groups,(CH3X(are(added.(It(leads(to(a(stable(
oxidized(product.(Eg.(Ir(I)(to(Ir(III)(CH3)X((
Reverse(reac&on(depends(on(the(stability(of(the(
oxidized(product(

Thermodynamics(of(OA(
Group(I(
If(two(electronega&ve(groups,(X2(are(added,(it(
leads(to(a(very(stable(oxidized(product.(
Reduc&ve(elimina&on(is(dicult((

Microscopic(Reversibility(GROUP(I(
(
+

CH3
OC

L
+

M
L

OC
CH3 - X(

1.(Expect(ioniza&on(of(the(product(
2.(AOack(of(the(XQ(on(the(CH3(group(
(

M
L

OC

CH3

MeOH

M
L

X-

II(Group(
O2, S2
RN3
acetylenes, S = C = S
RCON
ROCN
3
3(

o
Ir

one bond
retained.

In(principle(easy(to(
Reverse(the(reac&on!(
(
But(many(
intermediates(
undergo(some(
reac&on(or(other(

R
R

R
CpCo
-2L

CpCo
R

CpCoL2 + 2 RC CR

R
R

2L

R
R

+ Cp Co

When L = PPh3

Co

PPhR
3

CpCo
R

1. Intermediate isolated and characterised .

2. Shown to be catalytically active.
3. Kinetic analysis shows loss of PPh3 is Istep.
4. Replace PPh3 with PMe3 competely stops reaction.

III(Group(
No(mul&ple(bonds(/(Not(polar(
III group

agostic
H2

Ar - H
C-H

Si - H
R - SH

Polarity Small.
Splitting of H - H bond.
Cis(addi&on(of(the(addendum;(((No(intermediates(isolated(

CQH(ac&va&on!(
h(
C6F12
Ir
CO

CH4
CO

Graham(1983(
(
Bergman(1982(
Whitesides(1986(

Ir
CO

CH3
H

CoMe2I(PMe3)2(
Mechanis&c(Considera&ons(for(CC(Bond(
Reduc&ve(Coupling(at(a(Cobalt(III)(Center(

Hongwei(Xu(and(Wesley(H.(BernskoeOer*(
Department(of(Chemistry,(Brown(University,(Providence,(Rhode(Island(02912,(United(States(

dx.doi.org/10.1021/ja2072548(
J.(Am.(Chem.(Soc.(2011,(133,(1495614959(

Possible(paths(for(ethane(elimina1on(from(13Me2(

Possible(paths(for(ethane(elimina1on(from(13Me2(

Possible(paths(for(ethane(elimina1on(from(13Me2(

Reversible(PMe3(disssocia1on(prior(to(ethane(loss(

Reduc&ve(Elimina&on(
A(detailed(mechanis&c(study(of(CQO(
and(CQC(bond(forming(reac&on..(
Joy(M.(Racowski(allison(R(Dick(and(Melanie(S.(Sanford(
J.A.C.S.((Vol(131(10983,(2009(

Design(of(complex(B(for(C3O(bond3forming(reduc1ve(elimina1on(from(Pd(IV)(

93%(yield((

Possible(organic(products(of(reduc1ve(elimina1on(

Reduc1ve(elimina1on(from((Phpy)2Pd(IV)(OAc)2(

Possible(mechanisms(for(C3O(bond3forming(reduc1ve(elimina1on(from(I(

Crossover(experiments(

Selec1vity(of(C3O(bond3forming(reduc1ve(elimina1on(from(2b3d3(

Possible(mechanisms(for(C3O(bond3forming(reduc1ve(elimina1on(from(I(

Ra1onal(design(of(condi1ons(to(achieve(C3C(bond3forming((
reduc1ve(elimina1on(from((Phpy)2PdIV(O2CAr)2(

Suppressed(ioniza1on(
of(the(acid(leads(to(C3C(
bond3forming(
reduc1ve(elimina1on(
from(I(

Ioniza1on(of(the(acid(
leads(to(C3O(bond3
forming(reduc1ve(
elimina1on(from(I(

 Great(aspects(of(the(paper(
Very(well(behaved(system,(thoroughly(explored..(
Characteriza&on(of(intermediates(
Mul&ple(op&ons(explored(for(proving(a(point(

Microscopic reversibility predicts (1)

Several(surprises:(
(
1.

Low coordinated complexes are better for reductive elimination in some

cases. (dissociation precedes rxn.)

2.

Dinuclear complexes seem to be involved contrary to what is expected

from microscopic reversibility

OM(Q(18(

OM(Q(19(

Reduc&ve(Elimina&on(
Mechanism(of(the(reac&on(is(complex(
Dissocia&on(has(always(been(shown(to(be(
essen&al.(
Each(case(has(to(be(examined(carefully.(

Olefin Metathesis

A change in place
A represents a C with two
substituents like CR1R2
A

Likewise, B represents CR3R4

+
A

If R1 and R2 are methyl groups

For example, and If R3 and R4 are H
We have converted isobutylene to
Ethylene and 2,3 dimethyl butene!

Synthesis of insect pheromones herbicides,

better polymers and fuels.
Pharmaceuticals: including drugs for
treating bacterial infections, hepatitis C,
cancer, Alzheimers disease etc.

1. Amazing utility brought about by the

discovery of reliable catalysts for the
reaction.
2. Development of catalysts made feasible
by the understanding of the mechanism

Grubbs and Schrock

Epothilone

Surprising features!
The reaction is completely reversible.
The catalysts are often early transition
metal halides with aluminum alkyls as
reducing agents.
Both ingredients are very very water
sensitive! Yet a trace amount of water
helped!

Cyclobutane mechanism..
A

A
M

Coordination of the metal

makes it behave like AB*
A photoexcited olefin would
form a cyclobutane.

Is there precedence for

cyclobutane ring opening?

[Rh(CO)2Cl] 2

Quadricyclane and cubane ring opened!

Why cylclobutane mech. is

probably wrong
A

M
A

No cyclobutane is detected in
these reactions!.

Cyclobutanes
dont
form
olefins in the presence of
metals!

Ring opening happens through

a metallacycle!

Oxidative Coupling
alkenes instead of alkynes
C2
C1

C3

C4

C2 C3
C1
C4
M

C2

+
C1

C2

C3
M

C1

C3
M
C4

C4

After oxidative coupling a metal migration

should happen!

Cyclo-reversion of
metallocyclopentane..
C2
C1

C3

C4

C2 C3
C1
C4
M

C2

+
C1

C2

C3
M

C1

C3
M
C4

C4

After oxidative coupling a metal migration

should happen!

For metathesis, cyclo-reversion and

metal migration should happen
C2

C1

C3

C4

C2 C3
C1
C4
M

C2

+
C1

C2

C3
M

C1

C3
M
C4

C4

After oxidative coupling a metal

migration should happen reversibly!

Metallocyclopentane
C2 C3
C1
C4
M

C2
C1

C3

C1=C2, C3=C4

C2=C3, C1=C4

M
C4

R. H. Grubbs,
JACS, 1978, vol 100, p 1300

Metallocyclopentane
C2 C3
C1
C4
M

H3C

CH3

H3C
CH2

CH3
H2C

H3C

CH3

+
C2
C1

C3

M
CH2

M
C4

R. H. Grubbs,
JACS, 1978, vol 100, p 1300

Metallocyclopentane
H3C

CH3

H2C

D
WCl 6

Li

Li

CH3

H3C

Expected product if
happens. (not observed)
Maybe
it
is
thermodynamics..
version..

CH2

H2C

CH2

6%

DHC

CHD

6%

AlR3
H2C

R. H. Grubbs,
JACS, 1978, vol 100, p 1300

CHD

82 %

methathesis

a
question
of
So a labelled

If metathesis had happened,

one should get 1:1:2 ratio of
products

Metallocyclopentane
H

Li

Li

Cis isomer

WCl 6

H2C

CH2

6%

DHC

CHD

6%

AlR 3
H2C

CHD

Trans isomer gives stereospecifically the trans product!

Based on these experiments, the metallocylopentane
Mechanism for metathesis was discounted.

R. H. Grubbs,
JACS, 1978, vol 100, p 1300

Cis

82 %

A carbene mechanism
CD2
CH2

+
CH2

H2 C

CD2

H2C

CD2

H2C

CD2

CD2

CD2
H2 C

A diolefin complex becomes a tetracarbene complex

Then becomes a diolefin again

Precedence for forming a

carbene from olefin.
CCl 3

H
N

H
N

H
N

N
H

N
H

Heat
H

- CHCl3

N
H

H
N

H
N

H
N

+ Fe(CO) 5
N
H

N
H

Fe(CO) 4
N
H

Testing the carbene mechanism..

CH2
CH2

+
CH2

A clever alternative!
Now the metathesis will give
cyclohexene and ethylene

CH2

Testing the tetra-carbene

intermediate
CH2
CH2

+
CH2

CH2
M
CH2

CH2

CD2

CD2

+
CD2

CH2

CH2

CD2

CH2

CH2

Predicted ratios by tetracarbene

pathway
1 mole

CD2

CD2

Met.
Cat.

CD2

CH2

2 moles
CH2

CH2

CD2

0.5 moles

CD2

CH2
CH2

0.5 moles

Observed products in
metathesis..
CD2

CD2

1 mole
Met.
Cat.
CH2

CH2

CD2

CD2

0.5 moles
CH2

2 moles

CH2

CD2

CD2

CH2
CH2

0.5 moles

Non-pairwise exchange
R

H2C
R

CH

R
H2C

CH2
H2C

CH2

CH2

H2C

Chauvin & Herisson suggested and proved this first..

CH2

H2C

CH2

R
CH2

H2C

Non-pairwise exchange
Ph
W(OC) 5

O
H2C

W(CO) 5=C(OPh)Ph

Ph

Individual steps have been observed.

H2C

Tebbe reaction gives further support!

Can a metallocyclobutane
isomerize?

Intermediate was a
metallacyclobutane!

It was not phenyl group migration!

Although isomerization happens, the olefin cannot be exchanged!!

In this example where Tebbe reagent is used, the olefin exchange is also observed.
This suggests that the metathesis reaction at least with Ti can happen with this mech.

Chauvin & Herisson

http://nobelprize.org/nobel_prizes/chemistry/laureates/2005/info.pdf

Non-pairwise Mechanism

Non-pairwise mechanism!
H2C

CH2

CH2

M
R

R
CH2

H2C

Why did they get a Nobel Prize?

It has long been possible to produce new substances in
this way without understanding the catalysts role in the
reaction.
Here, researchers were given a new challenge to
grapple with: to construct new efficient catalysts.
Yves Chauvins reaction mechanism represents a great
step forward since it showed how the catalyst functions.
Robert H. Grubbs and Richard R. Schrocks took up this
challenge and fundamental research enters the picture.
Thanks to their contributions we have the catalysts that
are so useful today.

 Olefin metathesis
1. Ring closing
metathesis
2. Ring opening
metathesis
3. Cross metathesis
4. Ring opening
metathesis
polymerization
5. ADMET

Reference

Young-kwon Kim

ACIEE., 2000, 39, 3012

ACIEE., 1997, 36, 2036
JCS. PT1, 1998, 371
Tetrahedron. 1998, 54, 4413
Acc. Chem. Res. 1995, 28,
446

Cataly&c(Metathesis(

A(change(in(place(
A represents a C with two
substituents like CR1R2
A

+
A

Likewise, B represents CR3R4

If(R1(and(R2(are(methyl(groups((
For(example,(and(If(R3(and(R4(are(H(
(
We(have(converted(isobutylene(to((
Ethylene(and(2,3(dimethyl(butene!(

NonIpairwise(Mechanism(

NonIpairwise(mechanism!(
H2C

CH2

CH2

M
R

R
CH2

H2C

Catalysts(used(for(metathesis(

Discovered(in(Standard(Oil(Company(
Also(in(Phlipps(Petroleum((around(1950(

Carbenes(as(Catalysts(in(Metathesis(

Grubbs(Catalysts(

Improving(the(Grubbs(Catalyst(

2nd(Genera&on(Grubbs(catalyst(

HoveydaIGrubbs(Catalyst(

Lower(reac&vity,((More(stable..((

3rd.(Genera&on,(Grubbs..(

Ini&ates(metathesis(a(million(&mes(faster..(BeWer(polymers(

Searching(for(an(ideal(catalyst(
Schrocks(Ra&onal(Design(

Searching(for(an(ideal(catalyst(
Schrocks(Chiral((Catalyst(

Self(Metathesis(
AA(+(AA((((((((((((((((((((((((((((((((((AA(+(AA(
If(all(the(alkylidene(groups(are(the(same,(I(
would(call(it(self(metathesis.((
Reactants(and(products(are(the(same(

Cross(Metathesis(
AB((+(CD(((Can(give(
(
(AA,(AB,(AC,(AD,((
((((((((
(((((((((((((((((((((((((((((( (BB,(BC,(BD(
(((((((((((((((
(((((((((((((
(((((((((( (CC,(CD,((
( (
(
(
(
(DD(
if(the(alkylidene(is(symmetrical(it(can(lead(to(the(ten(
isomers(wriWen(earlier.(
Whereas(if(the(alkylidene(group(is(unsymmetrical,((
then(we(can(have(cis(and(trans,(eg.(CH3CH:(
So(a(maximum(of(20(alkenes(can(be(generated(from(
two(alkenes(and(4(alkylidene(groups.(
(

Controlling(Cross(Metathesis(

Cross(Metathesis(

92(%(yield((E/Z(=20(
(
R(=(AcOCH2(CH2)2(

(5(mol(%(

2(equivalents(

Steric(Factors(

100(

10(

5(

No(Reac&on(

Ring(Closing(Metathesis((RCM)(

Mechanism(of(RCM((

Mechanism(of(RCM((

Mechanism(of(RCM((

Ring(Opening(Metathesis(

Ethylene(gas(can(be(used(to(change(the(direc&on(of(the(reac&on(

Acyclic(Diene(Metathesis(
Polymeriza&on(

Concentra&on(of(the(diene(is(the(key!(

Polymeriza&on(is(a(compe&ng(process(
Lower(concentra&on(prevents((polymeriza&on(
Higher(temperature(also(promotes(ring(
closing!((((((S(increases.(
Remove(ethylene(if(you(want(ring(closing.(

Natural(product(synthesis(

hWp://upload.wikimedia.org/wikipedia/commons/0/05/
Fluvirucin_Synthesis_Olen_Metathesis.png(

Total&Synthesis&of&(+)2Manzamine&A&
(
Tatsuya(Toma(,(Yoichi(Kita(and(
Tohru(Fukuyama(*(
J.*Am.*Chem.*Soc.,(2010,(132((30),(pp(
1023310235(
DOI:&10.1021/ja103721s(

A(ringIclosing(metathesis(in(the(presence(of(
labile(func&onal(groups.(

Summary(
Metathesis(requires(a(carbene(/(carbyne(
complex(
NonIpairwise(exchange(is(common.(
Thermodynamics(is(the(key.((
Use(Le(Chateliers(principle(to(your(advantage.(
Temperature(and(concentra&on(have(to(be(
controlled.(