CATALYSIS I. THE HYDROFORMYLATION
REACTION
THE HYDROFORMYLATION REACTION



Oldest process still in use
Responsible for the production of materials from a
homogeneous catalyzed reaction
100% atom recovery
THE HYDROFORMYLATION REACTION
O
R
+
H2
+
CO
R
cat
R
H
"normal"
linear product
Fig. 7.1. The hydroformylation reaction
+
H
O
"iso"
branched product
HYDROFORMYLATION
THERMODYNAMICS
H2 + CH3CH=CH2 + CO  CH3CH2CH2C(O)H
G
63
-138
-117 (l)
= -42 kJ.mol-1
H
21
-109
-238
= -150 kJ.mol-1
H2 + CH3CH=CH2

CH3CH2CH3
G
63
-25
=
-88 kJ.mol-1
H
21
-105
=
-126 kJ.mol-1
COBALT CATALYZED HYDROFORMYLATION REACTION

A prototype homogeneous metal catalysis
- precatalyst to an active complex
- steps involving organometallic reactions
- 16 e to 18 e transition steps
- possible geometries of intermediates
STEP a
- Formation of the catalytically active
species (16 e) from HCo(CO)4
- HCo(CO)4 from Co2(CO)8 + synthesis gas
(CO + H2)
Reaction conditions:
(200 – 300 bar, 120-170oC)
STEP a
Preferred geometry of the intermediate: (based on
calculations)
STEP b
binding of the alkene to the active
catalyst
- forms 18 e complex
STEP b
Theoritical calculations indicate a slightly stable 4 (less steric
hindrance). Structure 5 has the requisite coplanar geometry for
Co, H, and the double bond C atoms)
STEP c
1,2 alky insertion
- reversible
-elimination is highly
possible but high CO
partial pressure will
stabilize the 18 ecomplex
STEP c
initial 16e complex
18 e complexes upon CO addition
Step d
CO insertion (1,2 alkyl
migration)
STEP d
18e
16e
STEP e
oxidative addition (H2)
–
reductive elimination
(product) sequence.
STEP e
8. Hydroformylation
A comment about metal-ligand ratio
Consider the following exercise. The catalytically active complex is involved
in the following equilibrium:
L + HM(CO)  LHM(L) + CO
The selective and fast catalyst species we want is HM(L) and we have
determined that at a certain pressure we need a twenty-fold excess of L in
order to have 95 % of M in the M(L) state.
The concentration of M = 10-3 molar. Suppose we want to reduce the
concentration of M to 10-5. What should we do with the concentration of L
(at constant pressure of CO). What ratio L/M should one choose?
What happens if the ratio is kept at 20?
(calculate the equilibrium constant from the first example and then calculate
the required concentration of L at M = 10-5 molar)
HYDROFORMYLATION
RHODIUM CATALYSTS, MONODENTATES
R
P
P
O
O
P
R
O
P O
O
O
SO3Na
R
tpp
tppms
"bulky" phosphite
UCC ligand
Hydroformylation
Hydroformylation with rhodium phosphite/phosphines
O
L4RhH
O
+
Linearity 40-96% depending on L
L4RhH
P(OEt)3
8% linear if L=
62% linear if L= P(OCH2CF3)3
O
BASF, L=PPh3
700 bar, 120 °C
L4RhH
L= bulky phosphite,
10 bar, 80 °C
L4RhH
<25 m/m/h
L= PPh3
4000 m/m/h
L= bulky phosphite
Results of rhodium catalysed hydroformylation with various ligands
Hydroformylation
Rhodium catalysts for propene
Rh/triphenylphosphine: linearity 60 to 96 %
Union Carbide Corporation, now Dow Chemicals
30 bar, at 120 °C, at high phosphine concentrations
linearity 92%.
300 mol.mol-1(Rh).h-1.
Low ligand concentrations, 10-20 mM, 1 mM Rh
10-20 bar and 90 °C
low linearities (70%),
5-10,000 mol.mol-1(Rh).h-1.
Rhodium TPP mechanism 1
L
H
L
Rh CO
OC
L
2ae
CO
H
Rh CO
L
CO
2ee
CO
H
OC Rh L
L
3c
L
L
L
H
L Rh L
CO
3t
H
Rh L
CO
1
8.3. Rhodium tpp mechanism, dimers
O
L
L
C CO L
Rh
CO
CO C
O
9
Rh
H2
L
H
L
Rh CO
OC
L
2ae
CO
H
L
Rh CO
L
CO
2ee
CO
H
OC Rh L
L
3c
Positive effect of raising H2 pressure
L
L
H
L Rh L
CO
3t
H
Rh L
CO
1
8.3. Rhodium cycle
L
H
Rh CO
OC
L
2ae
CO
CH3
CH2
O
L
H
L
Rh CO
L
L
CO
2ee
L
CO
H
H
OC Rh L
Rh L
CO
1
L Rh L
L
3c
C
H
H
CO
3t
C2H4
H
L
Rh
OC
H2
CH3
CH2
O
OC
Rh L
OC
L
8ee 8ae
4ae 4ee
CH3
CH2
O
CH3
CH2
C
C
CO
L
L Rh L
L Rh L
CO
CO
7c 7t
L
OC
CH3
CH2
Rh CO
L
6ae
L
L
CH3
CH2
Rh CO
CO
6ee
CO
5t 5c
8. Hydroformylation
Kinetics, overall
Scheme 6.1. Hydroformylation
MH(CO)
A
k1
k-1
(M=RhL3, L=any ligand, Ol=alkene)
MH + CO
B
k2
MH + Ol
B
MH(Ol)
C
MR + CO
D
MR(CO)
E
k-2
k3
k-3
k4
k-4
k5
k-5
MH(Ol)
C
MR
D
MR(CO)
E
MC(O)R
F
k6
MC(O)R + CO
F
MC(O)R + H2
F
k-6
MC(O)R(CO)
G
k7
MH + HC(O)R
B
product
Hydroformylation
Kinetics, resting state, type I
H
H(O)CC2H4R
CH2
L
CO
CO
Rh
CHR
L
CO
CO
resting state
H2
- CO
R
CH2
O
H
Rh
L
CO
L
CHR
CH2
CH2
Rh
L
CO
L
CO
R
CH2
CH2
L
Rh
L
2 CO
CO
rds, type I
8. Hydroformylation
Kinetics, rate equation, type I
equation d'Oro
v = k [C3H6]0.54[PPh3]-0.7[Rh]1
(conditions 90-110°C, 1-25 bar CO, 1-45 bar H2, PPh3/Rh ratio 300:1 to 7:1)
k1k2k3[Rh][C3H6]
v=
k1k2[C3H6] + k1(k-2 + k3) + k-1(k-2 + k3)[L]
“type I kinetics”
v=
kA [Rh] [C3H6]
kB + kC[CO]
8.2.2. Hydroformylation
Kinetics, resting state, type
II
H
H(O)CC2H4R
CO
CH2
L
CO
Rh
CHR
L
CO
rds, type II
CO
H2
R
CH2
O
O
CH2
L
CO
Rh
L
CO
R
CH2
- CO
CO
H
L
CHR
CH2
Rh
L
CH2
Rh
L
CO
L
CO
R
resting state
CH2
CH2
L
OC
Rh
L
CO
CO
8. Hydroformylation
Kinetics, rate equation, type II
rate expression Marko'
rate equation Garland
v=
v=k
[H2] [RhH(CO) 4]
[CO]
v = k [RC(O)Rh(CO)4]1[CO]-1.1[H2]1[3,3-DMB]0.1
k-6k7[Rh][H2]
k-6 + k6[CO] + k7[H2]
“type II kinetics”
conditions:
75°C
H2
33-126 bar
CO
40-170 bar
8.2.2. Rhodium tpp cycle, type I kinetics
electronic effects
2ae
Rate(type  I ) 
2ee
CO
CH3
CH2
O
3c
3t
C2H4
C
H
4ae
H2
O
migration
CH3
CH2
C
OC
Rh L
OC
L
8ee 8ae
5t 5c
7c 7t
CO
CO
migration
4ee
6ae
6ee
A[alkene][ Rh ]
B  [ L]
8.4. Rhodium complex isomers for regioselective
propene hf
H
PPh3
PPh3
Rh
H
H
PPh3
CO
PPh3
PPh3
Rh
PPh3
CO
OC
CO
ee
H
PPh3
Rh
H
PPh3
CO
linear aldehyde
PPh3
Rh CO
CO
Rh
CO
PPh3
ae
*
H
PPh3
Rh CO
PPh3
mixed aldehydes
H
OC
Rh CO
PPh3
8.4. Rhodium complex isomers; regioselectivity
PPh3
PPh3
H
Rh PPh3
CO
PPh3
PPh3
1
H
PPh3 Rh PPh3
CO
PPh3
H
Rh
CO
Rh CO
CO
4ee
linear aldehyde
OC
Rh CO
PPh3
OC
2ae
H
H
PPh3 Rh CO
PPh3
10c
PPh3
H
PPh3
2ee
PPh3 Rh CO
CO
3t
PPh3
H
H
Rh
CO
4e
H
OC Rh CO
PPh3
3c
PPh3
OC
H
Rh
PPh3
10t
OC
OC
4ae
mixed aldehydes
H
Rh
PPh3
4a
8. Steric effects for regioselective hf
Table 8.1. Hydroformylation of methyl-substituted 1-alkenes
Alkene
1-pentene
4-Me-1-pentene
4,4-Me2-1-pentene
3-Me-1-pentene
3,3-Me2-1-pentene
Rate, mol.mol-1.h-1 Linearity, %
11,300
9,300
5,300
9,600
7,600
78.4
78.0
85.0
91.0
99.0
Conditions: 90 °C, p(CO/H2) = 20 bar, [Rh]=0.5 mM, [PPh3]=5 mM, [alkene]=0.5 M,
initial rates at <20% conversion, no isomerization was observed [18].
8. Hydroformylation
Rhodium LPO stripping
propene, CO, H2
off-gas
de-mister
cooler
reactor
separator
regeneration
propene, CO, H2
catalyst
bleed
product
8.5. Hydroformylation
Rhodium LPO liquid
propene, CO, H2
off-gas
reactor
product
cooler
separator
regeneration
propene, CO, H2
catalyst
bleed
catalyst recycle
8.6. Hydroformylation
Rhodium tppts
SO3Na
P
NaO 3S
SO3Na
Ruhrchemie-Rhone Poulenc 1986
Propene and 1-butene
Same chemistry as tpp
8.7. Hydroformylation
Ruhrchemie-Rhône Poulenc process
exhaust
alkene
syngas
aldehyde
steam
water
syngas
8.8. Hydroformylation
one-phase, two phase
NMP
alkene
NMP,
org.,
cat.
water
product
org.,
NMP
extractions
NMP,
water,
cat
water
NMP,
cat
extractions
SO3Na
dist.
P
PPh2
tppms
DPBS
SO3Na
8.7. Hydroformylation
Summary of hydroformylation catalysts
Catalyst
Co
Co/phosphine
Rh/phosphine Pd/phosphine
Pressure, bar
Temperature, °C
200
140
70
170
30
120
Substrate
C3
C3
internal C10+
Product
aldehyde
Linearity, %
60-70
Alkane by-product, %2
Corrosion
+
Metal deposition
+
Heavy ends
+
Catalyst costs (Co=1) 1
C3,4
terminal
alcohol
70-90
10-15
+
+
+
10
60
100
all
aldehyde
70-95
0
1000
aldehyde
70-95
?
?
?
500
8. Hydroformylation
Rhodium catalyst isomers for propene
H
PPh3
PPh3
Rh
H
H
PPh3
CO
PPh3
PPh3
Rh
PPh3
CO
OC
CO
ee
H
PPh3
Rh
H
PPh3
CO
linear aldehyde
PPh3
Rh CO
CO
Rh
CO
PPh3
ae
*
H
PPh3
Rh CO
PPh3
mixed aldehydes
H
OC
Rh CO
PPh3
8. Hydroformylation
Mechanistic Scheme; Why Bidentates
H
H(O)CC2H4R
CH2
L
CO
CO
Rh
CHR
L
CO
CO
H2
- CO
R
L
CO
CH2
O
L
L
L
CO
H
H
CH2
Rh
L
Rh
CO
L
L
CHR
Rh
CH2
L
CO
CO
R
CH2
CH2
L
CO
L
CO
CO
Rh
CO
rearrangement
8. Hydroformylation
Novel bidentates
tBu
PPh2
O
P(OR)2
O
PPh2
P(OR)2
tBu
"BISBI"
Eastman, 1987
general formula of diphosphite
Union Carbide 1997
8.9. Table Ligand
8.1. Hydroformylation;
Novel bidentates
Bite
Rate
Ratio l:b
m.m–1.h–1
2550
3650
3200
3250
3800
600
angle
126
113/120
107
102
99
91
85
12
BISBI, 11
13
DIOP [also 56]
dppf [also 33]
dppp
dppe
PPh3a
2.6–4.3
25
4.4–12
4.0–8.5
3.6–5
0.8–2.6
2.1
2.4
6000
PPh2
PPh2
PPh2
11
PPh2
PPh2
12
PPh2
13
8. Hydroformylation
Rhodium diphosphine catalysts
BISBI
DIOP
dppf
O
Ph2 P
PPh2
Ph2 P
PPh2
Ph2 P
Bite angle 113 107
l/b ratio
66
12
O
PPh2
102
dppe
Fe
PPh2 PPh2
99
8.5
PPh2
85
2.4
Devon, 1987, Casey, 1992
13
Ph2 P
4-5
8. Hydroformylation
Novel bidentates 2
SO3Na
PAr2
NaO3S
SO3Na
NaO3S
PAr2
Ar =
SO3Na
BINAS
Hoechst/celanese Herrmann
8. Hydroformylation
Novel bidentates 3
O
PPh2
PPh2
Linear/ branched = 10
(patent to Shell, 1987)
8.10. Hydroformylation
Bite angles in Xantphos ligands
Si
P
O
PPh2
PPh2
PPh2
Homoxantphos (26) 102.0°
O
O
PPh2
Phosxantphos (27) 107.9°
PPh2
PPh2
Sixantphos (28) 108.5°
S
O
O
PPh2
PPh2
Thixantphos (29) 109.6°
PPh2
O
PPh2
Xantphos (30) 111.4°
PPh2
PPh2
Isopropxantphos (31) 113.2°
NR
O
O
PPh2
O
PPh2
R = H, Nixantphos (32) 114.1°
R = Bn, Benzylnixantphos (33) 114.2
PPh2
PPh2
PPh2
PPh2
Benzoxantphos (34) 120.6°
DPEphos (35) 102°
8. Hydroformylation
Geometry of bidentate Xantphos/rhodium
H
H
P
O
C
Rh
P
O
Ph3P
Rh
P
O
P
C
C
O
O
Fig. 6.15. Bis-equatorial coordination of Xantphos
Table 8.2. Hydroformylation
Bite angle effects in Xantphos ligands
Hydroformylation of octene-1 (1.2 M)
H
PR2
OC
Rh
O
X
R=
PR2
C
O
X
n
l/b
H, H
PPh
SiMe2
S
C=CMe2
102
105
109
111
112
7
18
34
41
50
8. Hydroformylation
Bite angle effects, steric hindrance
H
R
P
CO
Rh
H
R
P
P
Rh
CO
P
4ee
H
R
CO
OC
Rh
P
P
H
P
Rh
P
R
4ae
steric hindrance
8.3. Hydroformylation
dppf Electronic Ligand Effect
Hydroformylation with substituted aryl phosphines Fe[C5H4P(C6H4R)2]2
Ar=
i-value (Ar)
Ph
p-Cl-C6H4
m-F-C6H4
p-CF3-C6H4
4.3
5.6
6.0
6.3
linearity
%
84
87
89
92
relative rate
7.2
9.3
13.7
13.8
isomerization
% 2-hexene
4
5
5
6
(conditions 110°C, 8 bar CO/H2 = 1:1, 1-hexene, (Unruh and Christenson [14]),
R
R
P
Rh
Fe
P
R
R
for R see Table 6.1.
8. Hydroformylation & NMR
Electronic effects in Xantphos ligands
H
PR2
OC
Rh
O
S
R=
X
PR2
C
O
X=
-Rh
JH-Rh
JP-Rh
JP-H
rate
isom %
l/b
CF3
850
4.4
135
3.6
158
7
89
Cl
840
5.9
132
8.4
68
7
68
6.6
128
15
107
5
50
H
F
835
6.3
131
11
75
6
52
Me
831
7.3
126
18
78
5
44
MeO
825
7.3
125
21
45
6
37
8.12. Hydroformylation
Electronic effects in Xantphos ligands
4
2
1
H
3
PR2
OC
36
Rh
O
S
R=
X
PR2
C
O
37
38
29
IR spectra of complexes RhH(ligand)CO
(ligand = 36–41, 29)
39
40
41
2100
2000
1900
cm-1
H
8.12. Hydroformylation
IR of RhH(xant)(CO)2
H
OC
Ar2
P
Ar2
P
Rh
CO
O
CO
Rh
CO
S
P
Ar2
O
P Ar2
S
CO-eq-ap
CO-eq-eq
IR frequencies of complexes RhH(diphosphine)(CO)2
–1
–1
Substituent R
i-Value CO eq-ap (cm )
N(CH3)2
1.7
2027, 1960 (50%) 1983, 1935 (50%)
OCH3
3.4
2034, 1966
1990, 1942
H
4.3
2037, 1972
1994, 1946
F
5.0
2041, 1975
1997, 1950
Cl
5.6
2042, 1977
1999, 1952
CF3
6.4
2046, 1982 (90%) 2004, 1957 (10%)
CO eq-eq (cm )
Ar =
R
8.13. Hydroformylation
Linearity and isomerisation
CO, H2
RhLn
Linear
aldehyde
LnRhH
CO, H2
RhLn
Branched
aldehyde
8.14. Hydroformylation
Internal alkenes Table 8.4.
Ligand
Substrate
l:b ratiob
PPh3
2-octene
0.9
% linear
ald
46
31
9.5
90
65
32
9.2
90
112
0.3
23
2
31
6.1
86
15
32
4.4
81
20
PPh3
4-octene
O
O
P
P
P
P
O
31
O
32
120 °C
2 bar
t.o.fc.
39
Table 8.5. Hydroformylation
rhodium monophosphite
Ligand R3P
R=
n-Bu
n-BuO
Ph
PhO
2,6-Me2C6H3O
4-Cl-C6H4O
CF3CH2O
(CF3)2CHO
-value
q-value
4
20
13
29
132
109
145
128
linearity of
product %
71
81
82
86
28
33
39
51
190
128
115
135
47
93
96
55
8.15. Hydroformylation
Hydroformylation with rhodium bulky phosphite
H
CO
O
O
L
O
P
Rh
CO
CO
=L
Bulky phosphite, q = 170°, and its rhodium hydride complex
8. Hydroformylation
Novel bidentates
tBu
PPh2
O
P(OR)2
O
PPh2
P(OR)2
tBu
"BISBI"
Eastman, 1987
general formula of diphosphite
Union Carbide 1997
8.18. Hydroformylation
Bidentate phosphites
tBu
tBu
CO2Me
O
O
Ar =
P(OAr)2
tBu
O
P(OAr)2
CO2Me
41
O
tBu
O
P O
tBu
P O
O
tBu
tBu
42
tBu
8.17. Hydroformylation, diphosphites
tBu
H
O
C
P(OR)2
H
P
O
O
Rh
C
C
a
O
P(OR)2
C
tBu
O
P
b
O
O
C
Rh
O
H
O
C
Rh
P
O
P
c
O
O
8.17. Hydroformylation
Structure, NMR spectroscopy
H
Ph
Ph
CO
P
O
Rh
P
Ph
Me
N
CO
Ph
Ph
Me
Mortreux
Donor, apical; 4 atoms in bridge, yet a-e
8. Hydroformylation
Structures of dimers
O
H
P
2
CO
CO
Rh
P
P
Rh
Rh
+ H2
P
CO
P
P
CO
O
O
O
CO
P
P
Rh
Rh
P
CO
P
P
P
Rh
P
P
O
a
orange
+ 2 CO
Rh
O
b
red
8. Asymmetric Hydroformylation
CHO
CHO
[Rh]
+
CO/H2
R
t
1
R
t
O
O
O
P
R
2
2
t
Bu
Bu
O
SiR 3
P
O
R
1
Bu
2
O
t
UC-P2*
R
O P
O
O
O
R 3Si
P O
O
SiR 3 R 3Si
Bu
SiR 3
O
P
O
O
O
R 3Si
P O
O
SiR 3 R 3Si
2
R
8a (R = Me)
8b (R = Et)
8c (R = tert-Bu Me2)
9a (R = Me)
9b (R = Et)
9c (R = tert-Bu Me2)
8.21. Asymmetric Hydroformylation
Atropisomerism
P
O O
P
O O
8.22. Asymmetric Hydroformylation
Atropisomerism, bisnaphthol, match-mismatch
effects
SiR 3
O
P
O
O
O
R 3Si
P O
O
SiR 3 R 3Si
44a (R = Me)
44b (R = Et)
44c (R = tert-Bu Me2)
SiR 3
O P
O
O
O
R 3Si
P O
O
SiR 3 R 3Si
45a (R = Me)
45b (R = Et)
45c (R = tert-Bu Me2)
8.23. Asymmetric Hydroformylation
match-mismatch effects
BINAPHOS
PPh2
P
2
O
O
P
O
O
P
O
O
47 (R,S)
46 (R,S)-BINAPHOS
Me
Cl
Me
Me
PPh2
O
P
O
48(R)
PPh2
PPh2
O
O
O
Cl
P
O
P
O
O
Me
49a (S,R)
49b (R,R)
50 (R)
O
8.23. Asymmetric Hydroformylation
match-mismatch effects
BINAPHOS
Ligand
% e.e.
46 (S,R)
94 (S)
PPh2
2
O
46 (R,R)
25 (R)
47 (R,S)
85 (R)
P
O
P
O
O
49 (S,R)
83 (R)
94 (S)
47 (R,S)
Me
Cl
16 (R)
50 (--,R)
69 (S)
P
O
48(R)
PPh2
PPh2
Me
Me
PPh2
O
49 (R,R)
O
O
46 (R,S)-BINAPHOS
48 (R,--)
P
O
O
O
Cl
P
O
P
O
O
Me
49a (S,R)
49b (R,R)
50 (R)
O
8.23. Asymmetric Hydroformylation BINAPHOS
structure, ae!
H
Ph2
P Rh
CO
CO
O
P
O
O
JP-H
JP-Rh
JP-P
Exam III
March 7, Wed
6-7:30
Comprehensive Final Exam,
March 21 Wed. 7:30 -9:30 CTC 102
Write solubility product expressions for the following
compounds.
Ba3(PO4)2
PbI2
FePO4
Ag2S
Calculating Ksp from solubility data
The solubility of silver dichromate, Ag2Cr2O7, (molar
mass = 431.8 g/mol) in water is 1.59 g/L. Calculate
Ksp.
Calculating Ksp
The pH of a saturated solution of magnesium
hydroxide (milk of magnesia) was found to be 10.52.
From this, find Ksp for magnesium hydroxide.
Solubility from Ksp
What is the solubility of magnesium hydroxide in a
solution buffered at pH 8.80? Ksp Mg(OH)2 = 6.3 x
10-10
Common ion
What is the solubility (in grams per liter) of strontium
sulfate, SrSO4 (molar mass = 183.69), in 0.23 M
sodium sulfate, Na2SO4? Ksp = 3.2 x 10-7
PRECIPITATE?
A 0.150-L solution of 2.4 x 10-5M MgCl2 is mixed
with 0.050 L of 4.0 x10-3 M NaOH. Calculate Qc for
the dissolution of Mg(OH)2. No precipitate has
formed. Is the solution supersaturated, saturated, or
unsaturated? Ksp Mg(OH)2 = 5.2 x 10-24