The Use of Renewable
Feedstock in Organic
Synthesis
Dr. Lajos Ková
Kovács
Department of Medicinal Chemistry
University of Szeged, Hungary
Chemical Biology Course,
ourse, Seili,
Seili,
Finland
Tuesday, 26 August,
August, 2008
Chem. Eng. News, 86
(23), August 18,
2008: thematic issue
on Sustainability.
1
What is sustainable development?
“…sustainable development is development that meets the needs
of the present without compromising the ability of future
generations to meet their own needs.”
Brundtland Commission (1987): Our common future
Raw materials basis of chemical industry in a
historical perspective
F.W. Lichtenthaler,
S. Peters,
C. R. Chimie, 2004, 7,
65-90.
2
The amount and nature of annually produced biomass
World’s biomass production (t/a): 170−200×109
Lignocellulose: 50×109
Wood: 13×109
Cereals: 1.8×109
Starch:
1.1×109
Sugar:
0.17×109
Harvested wood:
1.55×109
Cellulose:
0.15×109
D-Glucose:
5×106
Paradigm shift and the ensuing conflicts
Energy
Fossil
materials
Biomass
Food
Chemicals
•
•
increasing use of biomass instead of fossil materials
potential competition between food, energy crops for
land use and carbon-based consumer products
(chemicals)
3
The World’s primary energy consumption, 1970 to 2025
G. A. Olah,
A. Goeppert,
G. K. S. Prakash:
Beyond Oil and Gas:
The Methanol
Economy, Wiley-VCH,
Weinheim, 2006
“The generation, storage, and transport of energy are among the greatest
challenges, if not the most formidable challenge at all, for years to come.”
A. Taubert, Guest Editor, in his Editorial for the special issue of International
Journal of Molecular Sciences devoted to "Energy Technology for the 21st
Century - Materials and Devices“, 2008,
http://www.mdpi.org/ijms/specialissues/energytec.htm
Oláh’s proposed solution: the methanol economy®
G. A. Olah, A. Goeppert, G. K. S. Prakash:
Beyond Oil and Gas: The Methanol Economy, Wiley-VCH, Weinheim, 2006
4
Challenges for a sustainable development
Replacement of fossil fuels for energy
Hydrogen economy (generation, storage, and transportation of H2),
solar power
Sustainable liquid (methanol, ethanol, etc.) economy
Production of carbon based consumer products from renewable resources
Cheap H2
Carbon dioxide (CO2)
Biomass
Using Nature for
CO2 conversion
Molecular level understanding of pollution prevention
Green chemistry
Sustainable and green chemistry
Chemistry
Green chemistry
Sustainable and
green chemistry
Sustainable chemistry
5
The principles of sustainable/green chemistry
Green chemistry is the utilization of a set of principles that reduces or
eliminates the use or generation of hazardous substances in the design,
manufacture, and applications of chemical products.
1. It is better to prevent waste than to treat or clean up waste after it is
formed.
2. Synthetic methods should be designed to maximize the incorporation
of all materials used in the process into the final product.
3. Wherever practicable, synthetic methodologies should be designed to
use and generate substances that process little or no toxicity to
human health and the environment.
4. Chemical products should be designed to preserve efficacy of
function while reducing toxicity.
5. The use of auxiliary substances (e.g. solvents, separation agents, etc.)
should be made unnecessary wherever possible and, innocuous when
used.
6. Energy requirements should be recognized for their environmental
and economic impacts and should be minimized. Synthetic methods
should be conducted at ambient temperature and pressure.
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998
The principles of sustainable/green chemistry
(continued)
7. A raw material of feedstock should be renewable rather than depleting
wherever technically and economically practicable.
8. Unnecessary derivatization (blocking group, protection/deprotection,
temporary modification of physical/chemical processes) should be
avoided whenever possible.
9. Catalysts (as selective as possible) are superior to reagents.
10. Chemical products should be designed so that at the end of their function
they do not persist in the environment and break down into innocuous
degradation products.
11. Analytical methodologies need to be further developed to allow for realtime, in-process monitoring and control prior to the formation of
hazardous substances.
12. Substances and the form of a substance used in a chemical process
should be chosen so as to minimize the potential for chemical accidents,
including releases, explosion, and fires.
Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998
6
Fossil vs. renewable materials
• Fossil (depleting) materials (petroleum oil, natural gas,
tar-sand, shale bitumen, coals) are mixtures of
hydrocarbons. When oxidized (combusted) they form
carbon dioxide (CO2) and water (H2O) and thus are not
renewable on the human scale.
• Renewable feedstocks (biomass), in contrast, will regrow annually. They are much more varied in their
composition (carbohydrates, vegetable oils and animal
fats, terpenes, lignins etc.). As a rule, they are usually
more oxygenated than their fossil counterparts.
Biomass use in more
detail
“The term “biomass” means any
organic matter that is available on a
renewable or recurring basis
(excluding old-growth timber),
including dedicated energy crops and
trees, agricultural food and feed crop
residues, aquatic plants, wood and
wood residues, animal wastes,
and other waste materials.”
B. Kamm, P. R. Gruber, M. Kamm
(2005): Biorefineries – Industrial
Processes and Products, in Ullmann’s
Encyclopedia of Industrial Chemistry,
Wiley-VCH, Weinheim, Vol. 4, p. 101133.
7
Model of a product flow-chart for biomass feedstock
Biology of bioconversion of solar energy into
biofuels
E. M. Rubin (2008): Genomics of cellulosic biofuels. Nature 454, 841-845 doi:10.1038/nature07190
8
Structure of
lignocellulose
E. M. Rubin (2008): Genomics of
cellulosic biofuels.
Nature 454, 841-845
doi:10.1038/nature07190
H
O
O
H O
O
H O
O
O H
O
H
O H
O
H
O
O
H O
O
O H
Products of a lignocellulosic feedstock biorefinery
9
The major biomass components as a renewable
feedstock for the chemical industry
•
Carbohydrates (cellulose, hemicellulose etc.)
75 %
•
Lignin
20 %
• Proteins, nucleic acids,
fats and oils, terpenes,
alkaloids etc.
•
5%
Only 3 to 3.5 % (ca. 6×109 t) of this amount is used in nonfood applications, e.g. chemistry
A. Corma, S. Iborra, A. Velty (2007): Chemical routes for the transformation of
biomass into chemicals. Chem. Rev., 107, 2411-2502.
Biotechnological sugar-based product family tree
10
The use of carbohydrates: pros and cons
• inexpensive materials
• available from virtually
inexhaustible, renewable
sources
• they are rich in chiral
centers
• too many hydroxyl groups
– most often protecting
groups are required
• too many chiral centers
• too few reactive
functional groups (C=C,
C=O)
• the price of more complex
carbohydrates has not
been competitive with
petrochemicals for a long
time
Carbohydrates: major transformation pathways
•
Chemicals from Fermentation Processes: Glucose Fermentation
–
–
–
–
–
Lactic Acid Platform
Succinic Acid Platform
3-Hydroxypropionic Acid Platform
Itaconic Acid Platform
Glutamic Acid Platform
•
Chemical Transformations of Monosaccharides
•
Chemical Transformation of Disaccharide (Sucrose etc.)
–
–
–
–
–
–
–
•
Dehydration of Monosaccharides
Hydrolysis
Esterification
Etherification
Oxidation
Glucosyl Shift: Production of Isomaltulose and Isomalt
Polymers
Polysaccharides
–
–
Depolymerisation
Deacetylation of Chitin
11
Glucose fermentation and oxidation
∆G (kcal/mol)
C6H12O6 + 2 Pi + 2 ADP → 2 CH3CH(OH)COOH + 2 H2O + 2 ATP
–47
C6H12O6 + 2 Pi + 2 ADP → 2 CH3CH2OH + 2 CO2 + 2 H2O + 2 ATP
–47
C6H12O6 + 6 O2 + 36 Pi + 36 ADP → 6 CO2 + 42 H2O + 36 ATP
–680
other fermentation
processes
Principal applications of lactic acid
O
HO
different
carbohydrates
Lactobacillus,
Bacillus,
and Rhizopus
bacteria
O
HO
OH
CH3
lactic acid
yn
pol satio
en
d
n
co
O
-H 2
EtO
H/
H+
-H
2O
CH3
O
O
O
CH3
O
OH
CH3
n
poly(lactic acid)
O
HO
O
CH3
ethyl lactate
(VertecTM)
CH3
biodegradable
polymer
> 140 000 t/a
environmentally
benign solvent,
replacement of
DMF, N-methylpyrrolidone,
acetone, toluene
other uses of lactic acid
12
The furan platform: furfural
O
O
pentosanes,
etc.
D-xylose
OH
tetrahydrofuran
furfurylalcohol
u
/C
H
H2
H2/Ni
H2/Ni
O
O
Pd (-CO)
O
H2/Ni
O
OH
furfural
furan
KOH
(Cannizzaro
reaction)
O
O
tetrahydrofurfurylalcohol
3 i
NH /N
1. . H 2
2
R
CO
3 H
H
C KO
O
O
O
R
NH2
OH
R = OH, furfurylideneacetic acid
furfurylamine
furan-2-carboxylic acid
(pyromucic acid)
R = alkyl, furfurylideneketones
The furan platform: 5-hydroxymethylfurfural 1.
O
O
O
HO
O
OH
O
HO
OH
O
2,5-bis(hydroxymethyl)furan
furan-2,5-dicarboxylic acid
O
2 /P
bP
t
O4
Mn
Ba
H2/Pt
O
furan-2,5-dicarboxaldehyde
1. NH2OH
2. H2/Ni
O
O
HO
100 °C
5-hydroxymethylfuran-2-carboxylic acid
O
H3C
ar
6b
14,
C, min
°
193 12 %
2-5 O 4
OH
H 2S
60-7
O
0%
4-oxopentanoic acid
(levulinic acid)
OH
H3C
O
Ag2O
OH
H2, Ru(acac)3, Bu3P
NH4PF6
H
OH
-H2O
O
4-hydroxypentanoic acid
(4-hydroxyvaleric acid)
O
HO
H2N
O
5-hydroxymethylfurfural
(HMF)
H
2,
NH2
2,5-bis(aminomethyl)furan
Cu
-R
u/C
215 °C, 31 bar
2-5% H2SO4,15 sec
H3C
O
O
O
H3C
hexoses
(D-fructose, D-glucose),
inulin, cellulose etc.
CH3
2,5-dimethylfuran
acac =
H3C
O
O
CH3
γ-valerolactone
(GVL)
13
γ-Valerolactone (GVL) from biomass
Research
octane
number
(RON): 130
I. T. Horváth, H. Mehdi, V. Fábos, L. Boda, L. T. Mika (2008): γ-Valerolactone a sustainable liquid for energy and carbon-based chemicals. Green Chem., 10,
238-242.
The furan platform: 5-hydroxymethylfurfural 2.
energy density (kWhL-1)
5-ethoxymethylfurfural (EMF): 8.7
ethanol: 6.1
gasoline: 8.8
diesel fuel: 9.7
M. Mascal, E. B. Nikitin, Angew. Chem. Internatl. Ed. Engl. (2008): Direct, highyield conversion of cellulose into biofuel, 47, published online: Aug 1 2008 4:00AM,
DOI: 10.1002/anie.200801594.
14
Dehydration of monosaccharides to furans and
levulinic acid
Glucosyl shift: production of artificial sweeteners
isomaltulose and Isomalt
OH
OH
6
HO
HO
Palatinit®,
C*Isomaltidex®
60 000 t/a
OH
O
HO
1
OH
HO
O
6
HO
OH
isomalt
OH
O
2
HO
OH
sucrose
Protaminobacter
rubrum
HO
OH
O
2
HO
1
HO
OH
O
O
Ni/H2
HO
HO
1
O
OH
O
6
HO
OH
OH
2
OH
isomaltulose
15
Glycosidase inhibitors used as drugs
H3C
HO
HO
HO
HO
HO
HO
HO
O
O
O
N
H
O
O
OH
OH HO
OH HO
OH HO
OH
R
N
HO
HO
HO
AcHN
HO
N
H
HO
acarbose
(Glucobay®/Precose®/Prandase®)
HO
OH
HO
OH
OH
voglibose
(Basen®/AO-128/Volix)
OH
H
O
O
AcHN
COOH
COOEt
OH
H2N
HN
NH
R = CH2CH2OH
miglitol (Glyset®/Diastabol®)
H2N
Zanamivir (Relenza®)
oseltamivir (Tamiflu®)
R= n-Bu
N-butyldeoxynojirimicin
(miglustat/Zavesca®)
Other industrial carbohydrate-based products
H
O
O
HO
surfactants
50,000 t/a
O
O
HO
OH
x
HO
O
n
HO
OH
alkyl polyglucosides (APG)
x = 0.3-0.7; n = 1-5
OR3
R4O
R8O
O
R7O
fat replacer (‘fatless’ fat)
dioxin sequestrant
O
O
6
R O
OR2
OR1
OR5
Olestra (Olean®)
R1...R8 = fatty acyl6-8/H2-0
16
D-Glucose
derivatives as
versatile building
blocks
F. W. Lichtenthaler, S.
Peters (2004):
Carbohydrates as green
raw materials for the
chemical industry. C. R.
Chimie 7, 65-90.
Vegetable oils, waxes and animal fats
•
Reaction of the Carboxy Group
–
–
–
–
•
Fatty Acids
Fatty Amines
Fatty Alcohols
Glycerol
Reaction of the Fatty Chain
– Epoxidation
– Ring-Opening of Epoxidized Fatty
Acid Derivatives
– Hydroformylation
– Dimerization
– Oxidative Cleavage and
Ozonolysis
– Metathesis Reactions
Picture © Craig Blacklock
17
Oleic acid to value added chemicals from
metathesis reactions
Terpenes
•
Pinene
–
–
–
–
–
•
Limonene
–
–
–
–
•
Isomerization: α-Pinene
Epoxidation of α-Pinene
Isomerization of α-Pinene Oxide
Hydration of α-Pinene: α-Terpineol
Dehydroisomerization
Isomerization
Epoxidation: Limonene Oxide
Isomerization of Limonene Oxide
Dehydroisomerization of Limonene and
Terpenes To Produce Cymene
Carene
–
–
–
–
Isomerization of Carene
Epoxidation of Carene
Isomerization of 2- and 3-Carene Oxides
Dehydroisomerization
•
Camphene
•
Citral
–
–
–
–
Epoxidation of Camphene
Aldol Condensations of Citral and Ketones
Baeyer-Villiger Oxidation: Melonal
Hydrogenation of Citral
Picture © Wikipedia
18
Some valuable
compounds that
can be obtained
from α- and βpinene
Vitamin A acetate:
> 3,000 t/a
Lignins
• Production of
dimethylsulfoxide
from lignins
• Synthesis of
vanillin
Picture © Craig Blacklock
19
The structure of lignins
•
Main components (monomers)
OH
•
Partial structure of a lignin
polymer
CH2OH
CH
HC
OH
OH
CH2OH
HC O Lignin
O
CH
CH2OH
CH
HCOH
CH3O
OH
CH3O
CHO
CH
HC
O
O
OH
p-coumaryl alcohol
O
OH
OH
coniferyl alcohol
CH3O
O
sinapyl alcohol
CH2OH
CH
HC OH
O
CH2OH
HC
HCOH
HOCH2
HC
HC
CH3O
O
OH
OCH3
CH3O
O
HOH2C C CHO
CH3O
CH2OH
CH
HO
H2COH
CH
HC
OH
HCOH
OCH3
O
OCH3
H2COH
HC O
H2C
HC
HC
O
CH
CH
CH2
HCOH
OCH3
O
OCH3
O
HOH2C CH O
3
HC
O
O
OCH3
O
HC O Carbohydrate
CH2OH
CH
HCOH
CH3O
OH
H2COH
HC
C O
O
OCH3
OCH3
OH [O-C]
Vanilin from lignin
•
•
•
•
As of 2001, the annual demand for vanillin was 12,000 tons, but only
1,800 tons of natural vanillin were produced
Except for the early times, synthetic vanilin is produced from
petrochemical sources (eugenol or guaiacol)
Vanilin is also produced from waste sulfite liquors from the cellulose
industry by alkaline oxidation
In the traditional process, >160 tons of caustic waste are produced
for every ton of vanillin manufactured
CHO
CHSO3[O]
alkaline oxidation
OCH3
OH
OCH3
OH
20
DMSO from lignine
CHSO3CHSO3
-
CHSO3
-
-
HS
+
OCH3
OH
CH3S-
OH
OCH3
(CH3)2S
NO2
(CH3)2SO
OH
OH
Lignosulfonates act as methylating agents
Selected readings 1. Books
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
R. J. Simmonds (1992): Chemistry of biomolecules: an introduction. Royal Society of Chemistry,
Cambridge.
B. G. Davis, A. J. Fairbanks (2002): Carbohydrate chemistry. (Series Ed: S. G. Davies. Oxford Chemistry
Primers, 99.) Oxford University Press, Oxford.
J. F. Robyt (1998): Essentials of carbohydrate chemistry. (Series Ed: C. R. Cantor. Springer advanced
texts in chemistry.) Springer Verlag, New York.
P. M. Collins, R. J. Ferrier (1996): Monosaccharides. Their chemistry and their roles in natural products.
John Wiley and Sons, New York.
S. Hanessian (Ed.) (1997): Preparative carbohydrate chemistry. Marcel Dekker, New York.
M. Bols (1996): Carbohydrate building blocks. John Wiley and Sons, New York.
J. N. BeMiller, R. L. Whistler, Eds. (1992): Industrial gums: polysaccharides and their derivatives.
Academic Press.
G. A. Olah, A. Goeppert, G. K. S. Prakash (2006): Beyond oil and gas: the methanol economy, WileyVCH, Weinheim.
F. Gunstone (2004): The chemistry of oils and fats: sources, composition, properties and uses. WileyInterscience, New York.
F. Shahidi Ed. (2005): Bailey's industrial oil and fat products. Volumes 1-6, 6th Edition, WileyInterscience, New York.
M. Pagliaro, M. Rossi (2008): Future of glycerol. New usages for a versatile raw material. Royal Society
of Chemistry, Cambridge.
T.-L. Ho (1992): Enantioselective synthesis: natural products from chiral terpenes. Wiley-Interscience,
New York.
E. Breitmaier (2006): Terpenes: flavors, fragrances, pharmaca, pheromones. Wiley-VCH, Weinheim.
P. T. Anastas, R. H. Crabtree Eds. (2008): Handbook of green chemistry - green catalysis. WileyInterscience, New York.
R. A. Sheldon, I. Arends, U. Hanefeld Eds. (2007): Green chemistry and catalysis. Wiley-Interscience,
New York.
P. Tundo, A. Perosa, F. Zecchini Eds. (2007): Methods and reagents for green chemistry: an
introduction. Wiley-Interscience, New York.
21
Selected readings 2. Reviews, papers and websites
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
A. Corma, S. Iborra, A. Velty (2007): Chemical routes for the transformation of biomass into chemicals. Chem. Rev.,
107, 2411-2502. See other papers in the same issue as well.
J. Szejtli (2004): Past, present, and future of cyclodextrin research. Pure Appl. Chem. 76, 1825-1845.
F. W. Lichtenthaler, S. Mondel (1997): Perspectives in the use of low molecular weight carbohydrates as organic raw
materials. Pure Appl. Chem. 69, 1853-1866.
F. W. Lichtenthaler (2002): Unsaturated O- and N-heterocycles from carbohydrate feedstocks. Acc. Chem. Res., 35,
728-737.
F. W. Lichtenthaler, S. Peters (2004): Carbohydrates as green raw materials for the chemical industry. C. R. Chimie
7, 65-90.
F. W. Lichtenthaler (2005): Carbohydrates in Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim,
Vol. 5, p. 79-122.
I. T. Horváth, H. Mehdi, V. Fábos, L. Boda, L. T. Mika (2008): γ-Valerolactone - a sustainable liquid for energy and
carbon-based chemicals. Green Chem., 10, 238-242.
H. Mehdi, V. Fábos, R., A. Bodor, L. T. Mika, I. T. Horváth (2008): Integration of homogeneous and heterogeneous
catalytic processes for a multi-step conversion of biomass: from sucrose to levulinic acid, γ-valerolactone, 1,4pentanediol, 2-methyl-tetrahydrofuran, and alkanes. Top. Catal., in press.
Y. Román-Leshkov, C. J. Barrett, Z. Y. Liu, J. A. Dumesic (2007): Production of dimethylfuran for liquid fuels from
biomass-derived carbohydrates. Nature, 447, 982-986.
H. Zhao, J. E. Holladay, H. Brown, Z. C. Zhang (2007): Metal chlorides in ionic liquid solvents convert sugars to 5hydroxymethylfurfural. Science, 316, 1597-1600.
M. Mascal, E. B. Nikitin, Angew. Chem. Internatl. Ed. Engl. (2008): Direct, high-yield conversion of cellulose into
biofuel, 47, published online: Aug 1 2008 4:00AM, DOI: 10.1002/anie.200801594.
E. M. Rubin (2008): Genomics of cellulosic biofuels. Nature 454, 841-845 doi:10.1038/nature07190.
B. Kamm, P. R. Gruber, M. Kamm (2005): Biorefineries – Industrial Processes and Products, in Ullmann’s
Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, Vol. 4, p. 101-133.
Innovating for a better future. Putting sustainable chemistry into action. Implementation action plan 2006.
http://www.suschem.org/
Biotechnology Industry Organization (2006): Achieving sustainable production of agricultural biomass for biorefinery
feedstock. http://www.bio.org/
Chem. Eng. News, 86 (23), August 18, 2008: thematic issue on Sustainability.
Availability of this lecture
• http://www.mdche.uszeged.hu/~kovacs/renewables_Seili.pdf
• [email protected]
22