Advanced Catalysis and Organometallic Chemistry,
Chemistry,
Camerino,
Camerino, 16.08. – 27.08.2009
• Green chemistry
- Why green chemistry
- Green chemistry principles
- Ionic liquids as green solvents
- Ionic liquids as active components of the catalytic system
- Highly selective catalysis
- Alternative feedstock
SYNTHESIS of NEW COMPOUNDS
IS
a EXCLUSIVE DOMAIN of CHEMISTRY
(characterization, interactions studies, manipulations, transformations)
1
Efficiency, atom economy, E – factor
B.Trost, R. Sheldon
Σ waste
E=
(kg/kg)
Σ product
E-1 =
Σ substrates
(kg/kg)
Σ product
Product
bulk chemicals
Material factor
Production (ton)
E
< 104 – 106
<1–5
2
4
fine chemicals
10 - 10
pharmaceuticals
10 – 103
6
10 - 10
oil refining
Ecologic factor
5 – 50
25 – 100
8
0.1 - 1
Efficiency, atom economy – E - factor
(example)
stoichiometric reagents
3
+ 2 CrO3 + 3 H2SO4
3
+ Cr2(SO4)3 + 6 H2O
waste
O
OH
benzophenone
diphenyl methanol
392 g mol-1
18 g mol-1
182.2 g mol-1
3 x 182.2
-
392 + 6 x 18
1
-
x
E = 0.915
X = 0.915
1 kg of product - 0.915 kg waste
2
Efficiency, atom economy – E - factor
(example)
stoichiometric
stoichiometric reagents
3
+ 2 CrO3 + 3 H2SO4
3
+ Cr2(SO4)3 + 6 H2O
waste
O
OH
benzophenone
diphenyl methanol
182.2 g
392 g mol-1
18 g mol-1
E = 0.915
mol-1
catalytic
[catalyst]
+ H2O
+ O2
O
OH
benzophenone
diphenyl methanol
Strategic
goal
Sustainable
development
Practical
approaches
Operational
tools
Green
chemistry
Catalysis
Green
engineering
Waste
management
Industrial
ecology
Proces
intensification
Renewable
energy
E = 0.099
Monitoring
tools
Life-cycle
assessment
Sustainable development: meeting the
needs of the present generation without
compromising the ability of future
generation to meet their own needs.
E-factor,
atom economy
3
NEW PROCESSES
IMPROVEMENT of the KNOWN PROCESSES
SEARCHING for the NEW PROCESSES
ROLE of CATALYSIS
CATALYSIS IS A MAIN TOOL OF GREEN
CHEMISTRY
EVOLUTION of the ENVIRONMENTAL
MOVEMENT
* dilution is the solution to pollution
(but bioaccumulation, chronic toxicity)
* waste treatment through command and control
- waste treatment prior to release
- exposure control
- abatement of the wastes subsequent to their release
4
„GREEN CHEMISTRY”
CHEMISTRY”
Green chemistry efficiently utilizes (preferably
renewable) raw materials, eliminates waste and avoids the use
of toxic and/or hazardous reagents and solvents in the
manufacture and application of chemical products.
(P. Anastas, T. Warner)
Green chemistry eliminates waste at source, i.e. it is
primary pollution prevention rather than waste remediation.
Green chemistry = environmentally friendly chemical synthesis
Sustainability is the goal and green chemistry is the means to
achieve it.
Green chemistry principles
(P. Anastas and T. Warner, Green Chemistry, Theory and Practice, Oxford Univ. Press, 1998)
1.
Prevent waste instead of treating it.
2.
Design atom-efficient synthetic methods.
C
3.
Choose synthetic routes using nontoxic compounds where possible.
C
4.
Design new products that preserve functionality while reducing toxicity.
5.
Minimize the use of auxiliary reagents and solvents.
C
6.
Design processes with minimal energy requirements.
C
7.
Preferably use renewable raw materials.
8.
Avoid unnecessary derivatization.
9.
Replace stoichiometric reagents with catalytic cycles.
10. Design new products with biodegradable capabilities.
C
C
C
11. Develop real-time and on-line process analysis and monitoring methods.
12. Choose feedstocks and design processes that minimize the chance of accidents.
5
EXAMPLES of APPLICATION of GREEN CHEMISTRY
PRINCIPLES in CATALYTIC REACTIONS
Atom economy - principle 2
Example: hydroformylation
R-CH=CH2 + CO + H2
cat.
O
R-CH2-CH2-CH + R-CH-CH3
C-H
100% atom economy
O
Catalysts:
HRh(CO)(PPh3)3
Rh(acac)(CO)2
Rh(acac)(CO)(PPh3)
Rh(acac)[P(OPh)3]2
6
Use of catalyst,
catalyst, innocuous solvent
Synthesis of cinnamic acid in H2O
(UV filters,
filters, fragnances)
fragnances)
I
[Pd]
COOH
+
COOH
KOH, H2O
92 %
Heck reaction
O
[Pd] = i.e. PS - PEG - NH -C
PPh2
Pd
Cl
Y. Uozumi, J.Org.Chem., 1999
Use of catalytic reactions
Synthesis of Naproxen and Ibuprofen (antiflamable drugs)
drugs)
Br
+ Br2
AcOH
CH3O
[Pd]
CH3O
Heck reaction
[Pd]
CO, H2O
CH3O
COOH
CH3O
carbonylation reaction
Naproxen
[Pd]
COOH
CO, H2O
carbonylation reaction
Ibuprofen
[Pd] = PdCl2(PPh3)2
Nippon Petrochemicals Comp. Ltd., Ethyl Corp., Montedison, Albermarle
7
Two methods of ibuprofen synthesis
O
O
O
O
Cl
O
O
OEt
O
AlCl3
H2O
NaOEt
H3O+
NH2OH
H
CN
N
O
O
OH
O
COOH
O
O
H2
CO
OH
ibuprofen
Pd
HF
Ni Raney
Green Chemistry Award, 1997
A CASE of THALIDOMIDE
O
O
O
O
NH
N
O
S - THALIDOMIDE
HN
O
O
N
O
R - THALIDOMIDE
Most of biological processes are stereospecific but usually only one optical
isomer of a chiral compound is responsible for desired biological activity
8
ASYMMETRIC CATALYSIS
(hydrogenation)
COOH
COOH
+
NHAc
H2
[Rh(dipamp)(cod)]+
2-propanol
AcO
NHAc
AcO
OMe
OMe
H3O+
Ph
MeO
COOH
P
P
OMe
Ph
NH2
HO
OH
dipamp
L - DOPA
(for Parkinson therapy)
pharmaceuticals
Use of catalytic reactions
Synthesis of Naproxen and Ibuprofen
in asymmetric hydrogenation
COOH
+ H2
CH3O
*
RuCl2(S-BINAP)
[bmim]BF4/iPrOH
COOH
CH3O
(S) - Naproxen
COOH
+ H2
Ru(OAc)2(S-BINAP)
*
COOH
[bmim]PF6/MeOH
(S) - Ibuprofen (85 % ee)
PPh2
PPh2
S - Binap
9
IONIC LIQUIDS AS REACTION MEDIUM
of C-C CROSS-COUPLING
IONIC LIQUIDS
Ionic liquids are liquids fully composed of ions.
Ionic liquids are fluid around 100oC.
[HNEt3]NO3 – the first room – temperature ionic liquid was
obtained in 1914 by Paul Walden
10
Examples of ionic liquids
R1, R2,
R1
N
+
N
Anion
name
R1 = R2 = CH3
Cl
125
mmim
R1 = CH3, R2 = C4H9
Cl
65
bmim
R1 = CH3, R2 = C2H5
Cl
87
emim
Br
81
PF6
62
NO2
55
R2
BF4
CF3SO3
R1
tt (oC)
R1 = CH3, R2 = C4H9
+
N
R2
Cl
6
-9
158
PF6
45
BF4
< 20
R = CH3
Br
C2H5
Br
284
C4H9
Br
124
C6H13
Br
99
C8H17
Br
95
[NR4]+
bmpy
> 300
Widely tunable properties of ionic liquids
• high thermal stability
• little/no vapour pressure
• good solvents for organic and inorganic compounds
• good solvents for gases
• non-flammable
• possibility to use in multiphasic systems
• coordination ability dependent on the kind of anion and cation
• ability to form carbene complexes with transition metals
P. Wasserscheid, W. Keim, 2000; R. Sheldon, 2001; W.Herrmann, 1995; J. Dupont, 1998; T. Welton, 1999; J. Dupont, 2002;
H. Olivier – Bourbigou, 2002
11
Examples of C-C bond forming reactions in
which ionic liquids can be used as solvents
Scheme
Reaction
O
X
carbonylation
[Pd]
+ CO + NuH
R
[Pd]
H +X
Sonogashira
ONu
R
R
Suzuki
R
[Pd]
+ X
(OH)2B
R
R
R
X
Heck
+
R
[Pd]
C(O)OR
C(O)OR +
R
C(O)OR
R
trans
AminoAmino- and alkoxycarbonylation of iodobenzene
I
+ Et2NH + CO
C(O)NEt2
+
Pd(OAc)2/4 PPh3
base, IL
N,N - diethylbenzamide
NuH = Et2NH (= base)
I
+
iPrOH
+ CO
solvent
C(O)C(O)NEt2
N,N - diethylphenylglioxamide
yield (%)
NEt2H
18
82
[bmim]BF4
17
83
[bmim]PF6
24
76
C(O)OiPr
+
Pd(OAc)2/4 PPh3
base, IL
α - keto propyl benzoate
propyl benzoate
NuH =
iPrOH
solvent
C(O)C(O)OiPr
yield (%)
iPrOH
5
7
[bmim]BF4
58
25
[bmim]PF6
93
6
M. Tanaka, Green Chem., 2001
12
Pd(0) COLLOID CATALYZED HECK REACTION in
MOLTEN SALT
Br
+
[Pd(0)] colloid
C(O)OBu
C(O)OBu +
C(O)OBu
130oC, 4 h
trans
1
2
[PhBr] : [acrylate] = 2.3
Catalyst
yield (%)
1
2
Pd(0) colloid
28
0
Pd(0) colloid / [Bu4N]Br
37
67
Trzeciak, Ziółkowski, 2005
Suzuki reaction under sonochemical conditions
R
B(OH)2
R
N
N
Pd
N
X
+
.
N
R
2 BF4
R
R
)))))), 30oC
R
R
Pd(OAc)2
[bbim]BF4
))))))
R
N
N
Pd
N
R
Substrate
time(min)
iodobenzene
4-methoxyiodobenzene
4-chloroiodobenzene
bromobenzene
4-methoxybromobenzene
chlorobenzene
20
20
30
45
10
60
N
.
2 BF4
R
yield(%)
92
93
85
82
85
42
R. Rajagopal, D.V. Jarikote, K.V. Srinivasan, Chem. Comm., 2002
13
Sonogashira reactions in ionic liquids under
sonochemical conditions
PdCl2, NEt3
+ I
H
))))), [bbim]BF4
Reaction yield in subsequent cycles (%)
(1)
(2)
(3)
(4)
(5)
93
91
89
88
85
K.V. Srinivasan i inni, J. Org. Chem., 2005
SONOGASHIRA REACTION in IONIC LIQUIDS
H
[PdCl2(P(OPh)3)2]
+ I
NEt3 IL
IL
Wydajność
Wydajność %
[bmim]PF6
C8H17
N
N
0
+
N
+
N
[mokt]Cl
[mokt]PF6
C4H9
83
H3C
100
bmim
H3C
mokt
RECYCLING of CATALYST (possible
(possible in IL only)
only)
100
yield %
75
50
[bmim]PF6
[mokt]PF6
25
0
Trzeciak, Ziółkowski, 2006
1
2
3
4
cycle
14
Recycling of Pd catalysts in [bmpy]BF4
O
I
[Pd]
+ MeOH + CO
OMe
NEt3, [bmpy]BF4
CH3
100
wydajność %
+
N
C4H9
bmpy
50
0
I
II
III
IV
PdCl2(COD)
V
Pd(0)coll.
Trzeciak, Ziółkowski, 2004
Yield of methylbenzoate obtained in
methoxycarbonylation of iodobenzene in IL
O
I
[Pd]
+ MeOH + CO
NEt3
OMe
IL
% yield
100
50
0
l
(b
m
py
)P
F
(b
m
py
)B
py
(b
m
)C
6
F4
6
]P
F
im
[b
m
]B
im
[b
m
[b
m
im
]C
F4
l
C8
C7
C6
Br1
C5
N2
Pd
C3
C1
C2
Br2
N1
C4
Pd/PVP
PdCl2(COD)
(bmim)2PdCl4
[bmim]2[PdBr4]
Trzeciak, Ziółkowski, 2004, 2006
15
NEGATIVE EFFECT of [bmim]X on
METHOXYCARBONYLATION - reaction with PdPd-aryl complex
[Pd0]
+ ArX
IL
PdII
-
when IL =
Ar
N
X
+N
Clor
Br-
N
Cl
(Br)
ArH
CO
N
Pd
X
N
+N
Cl
(Br)
Ar
C=O
PdII
X
[Pd0] = [Pd(0)L3,4] or Pd0 colloid
Zawartka, Trzeciak, Ziółkowski, 2008
Advantages of ionic liquids application
(principles 3, 5 and 9)
-
replacement of VOC (volatile organic compounds)
- easy separation of catalyst from organic products
16
Immobilized ionic liquids
OH
P
N
P
P
Cl
N
OH
+
ClN
P
N
N
+
CO2Me
P
O
N ClN
ClN
+
CO2Me
N Cl-
N
P
+
O
N +
N Cl
ALTERNATIVE FEEDSTOCK
17
Adipic acid
Du Pont process
E. Coli cell
OH
H2
O
Ni/Al2O3
5000 kPa
CO2H
OH
O
OH
OH
O
OH
OH
OH
D-glucose
O2
CO2H
Co, 160oC
900 kPa
O
OH
OH
HO2C
+
OH
OH
OH
catechol
HNO3
Cu, NH4NO3
CO2H
O
muconic acid
HO
OH
O
Alternative (agricultural) feedstock
hydroxyacids
acetaldehyde
peracetic acid
Kraft black
liquor
Waste
material
lignin
antraquinone
acrylic acid
Potato waste
Fermentable
sugars
lactate
esters
peracid esters
18
Lonza process – synthesis of nicotinamide
NH2
H2N
zeolite
[Pd]
- NH3
- 3 H2
N
H
N
O
CN
O2/NH3
oxide cat.
N
C
H2O
Rhodococcus rhodocrous
NH2
N
vitamin B3
C6H16N2 + 3/2 O2
C6H6N2O + 2 H2O + 3 H2
catalysis and biocatalysis
19