1

The Use of Renewable The Use of Renewable The Use of Renewable The Use of Renewable

Feedstock in Organic Feedstock in Organic Feedstock in Organic Feedstock in Organic

Synthesis Synthesis Synthesis Synthesis

Dr. Dr. Dr. Dr. LajosLajosLajosLajos KovKovKovKováááácscscscs

DepartmentDepartmentDepartmentDepartment ofofofof MedicinalMedicinalMedicinalMedicinal ChemistryChemistryChemistryChemistry

UniversityUniversityUniversityUniversity ofofofof Szeged, HungarySzeged, HungarySzeged, HungarySzeged, Hungary

Chemical Biology Chemical Biology Chemical Biology Chemical Biology CCCCourseourseourseourse, , , , SeiliSeiliSeiliSeili, , , , FinlandFinlandFinlandFinland

Tuesday, 26 AugustTuesday, 26 AugustTuesday, 26 AugustTuesday, 26 August, 2008, 2008, 2008, 2008

Chem. Eng. News, 86(23), August 18,

2008: thematic issue on Sustainability.

2

What is sustainable development?

“… sustainable development is development that meets t he needs of the present without compromising the ability of future generations to meet their own needs.”

Brundtland Commission (1987): Our common future

F.W. Lichtenthaler,S. Peters,C. R. Chimie, 2004, 7, 65-90.

Raw materials basis of chemical industry in a historical perspective

3

The amount and nature of annually produced biomass

World’s biomass production (t/a): 170−200×109

Sugar:0.17×109

Wood: 13×109

Lignocellulose: 50×109

Harvested wood:1.55×109

Cellulose:0.15×109

Cereals: 1.8×109

Starch:1.1×109

D-Glucose:5×106

Paradigm shift and the ensuing conflicts

BiomassFossilmaterials

Energy

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)

4

G. A. Olah,A. Goeppert,G. K. S. Prakash: Beyond Oil and Gas: The Methanol Economy, Wiley-VCH, Weinheim, 2006

The World’s primary energy consumption, 1970 to 2025

“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

5

Challenges for a sustainable development

Production of carbon based consumer products from renew able resources

Carbon dioxide (CO 2)

Biomass

Molecular level understanding of pollution preventi on

Green chemistry

Using Nature forCO2 conversion

Cheap H2

Replacement of fossil fuels for energy

Hydrogen economy (generation, storage, and transportat ion of H 2),solar power

Sustainable liquid (methanol, ethanol, etc.) economy

Sustainable and green chemistry

Chemistry

Sustainable chemistry

Green chemistry

Sustainable andgreen chemistry

6

The principles of sustainable/green chemistryGreen 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 c lean up waste after it isformed.

2. Synthetic methods should be designed to maximize the incorporationof all materials used in the process into the final product.

3. Wherever practicable, synthetic methodologies sh ould be designed touse and generate substances that process little or no toxicity tohuman health and the environment.

4. Chemical products should be designed to preserve efficacy offunction while reducing toxicity.

5. The use of auxiliary substances ( e.g. solvents, separation agents, etc.)should be made unnecessary wherever possible and, i nnocuous whenused.

6. Energy requirements should be recognized for thei r environmentaland economic impacts and should be minimized. Synt hetic methodsshould be conducted at ambient temperature and pres sure.

Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998

(continued)

7. A raw material of feedstock should be renewable r ather than depletingwherever technically and economically practicable.

8. Unnecessary derivatization (blocking group, prot ection/deprotection,temporary modification of physical/chemical process es) should beavoided whenever possible.

9. Catalysts (as selective as possible) are superio r 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 do wn into innocuousdegradation products.

11. Analytical methodologies need to be further dev eloped to allow for real-time, in-process monitoring and control prior to th e formation ofhazardous substances.

12. Substances and the form of a substance used in a chemical processshould be chosen so as to minimize the potential fo r chemical accidents,including releases, explosion, and fires.

Anastas, P. T.; Warner, J. C. Green Chemistry: Theory and Practice, Oxford University Press, Oxford, 1998

The principles of sustainable/green chemistry

7

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 re-grow 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’sEncyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim, Vol. 4, p. 101-133.

8

Model of a product flow-chart for biomass feedstock

E. M. Rubin (2008): Genomics of cellulosic biofuels. Nature 454, 841-845 doi:10.1038/nature07190

Biology of bioconversion of solar energy into biofuels

9

Structure of lignocellulose

E. M. Rubin (2008): Genomics of cellulosic biofuels.

Nature 454, 841-845 doi:10.1038/nature07190

OO O

OO

OOO OH

H

OO

OH

O O

O

H

H

H

H

H

H

Products of a lignocellulosic feedstock biorefinery

10

The major biomass components as a renewable feedstock for the chemical industry

A. Corma, S. Iborra, A. Velty (2007): Chemical routes for the transformation of biomass into chemicals. Chem. Rev., 107, 2411-2502.

• 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 non-food applications, e.g. chemistry

Biotechnological sugar-based product family tree

11

The use of carbohydrates: pros and cons

• inexpensive materials• available from virtually

inexhaustible, renewable sources

• they are rich in chiralcenters

• 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– Dehydration of Monosaccharides

• Chemical Transformation of Disaccharide (Sucrose etc.)– Hydrolysis– Esterification– Etherification– Oxidation– Glucosyl Shift: Production of Isomaltulose and Isomalt– Polymers

• Polysaccharides– Depolymerisation– Deacetylation of Chitin

12

Glucose fermentation and oxidation∆G (kcal/mol)

C6H12O6 + 2 Pi + 2 ADP → 2 CH3CH(OH)COOH + 2 H2O + 2 ATP –47C6H12O6 + 2 Pi + 2 ADP → 2 CH3CH2OH + 2 CO2 + 2 H2O + 2 ATP –47C6H12O6 + 6 O2 + 36 Pi + 36 ADP → 6 CO2 + 42 H2O + 36 ATP –680

other fermentationprocesses

Principal applications of lactic acid

Lactobacillus,Bacillus,

and Rhizopusbacteria

differentcarbohydrates

HO

CH3

O

OH

lactic acid

HO

CH3

O

O

CH3

O

OOH

CH3

O

HO

CH3

O

O

poly(lactic acid)

ethyl lactate(Vertec TM)

CH3

poly-

condensation

-H 2O

EtOH/H +

-H2 O

n

biodegradablepolymer

> 140 000 t/a

environmentally benign solvent, replacement of DMF, N-methyl-

pyrrolidone, acetone, toluene

other uses of lactic acid

13

The furan platform: furfural

O

O

pentosanes,D-xylose etc.

furfural

O

O OOH

furfurylalcohol

OOH

tetrahydro-furfurylalcohol

ONH2O

OH

OO

R

O

H

furfurylaminefuran-2-carboxylic acid

(pyromucic acid)

R = OH, furfurylideneacetic acid

R = alkyl, furfurylideneketones

furan

tetrahydrofuran

KOH(Cannizzaroreaction)

H 2/C

u

H2/Ni

H2/Ni

1. NH3

2. H2 /Ni

Pd (-CO)

CH 3COR

KOH

H2/Ni

The furan platform: 5-hydroxymethylfurfural 1.

O

OHO

hexoses(D-fructose, D-glucose),

inulin, cellulose etc.

5-hydroxymethylfurfural(HMF)

215 °C, 31 bar2-5% H2SO4,15 sec

H3C O CH3

OOHHO

OOHHO

ONH2H2N

OOO

2,5-dimethylfuran

O

OOHHO

OO

furan--2,5-dicarboxaldehyde

4-oxopentanoic acid(levulinic acid)

2,5-bis(hydroxymethyl)furanfuran-2,5-dicarboxylic acid

5-hydroxymethylfuran--2-carboxylic acid

2,5-bis(aminomethyl)-furan

O

H3CO

OH

OH

H3CO

OH H3C OO

4-hydroxypentanoic acid(4-hydroxyvaleric acid)

γ-valerolactone(GVL)

Ag2O

100 °C

1. NH2OH2. H2/Ni

H2/Pt

O2 /Pb-Pt

H2 , Cu-Ru/C193 °C

, 14,6 bar

12 min

H2, Ru(acac)3, Bu3PNH4PF6

2-5%

H 2SO 4

BaMnO 4

60-70%

H

-H2O H3C CH3

O Oacac =

14

γ-Valerolactone (GVL) from biomass

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.

Research octane number

(RON): 130

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.

The furan platform: 5-hydroxymethylfurfural 2.

energy density (kWhL-1)5-ethoxymethylfurfural (EMF): 8.7

ethanol: 6.1gasoline: 8.8

diesel fuel: 9.7

15

Dehydration of monosaccharides to furans and levulinic acid

Glucosyl shift: production of artificial sweeteners isomaltulose and Isomalt

HO

OH

OH

O

OH

O

OHHO

HO

HOO

O

OHHO

HO

HOO

OH

OH

OHHO

OH

isomalt

OH

OHHO

OO OH

OHHO

HO

HOO

isomaltulose

sucrose

Protamino-bacterrubrum

2

6

1

1

6 2

Ni/H2

1

2

6

Palatinit®,C*Isomaltidex®

60 000 t/a

16

Glycosidase inhibitors used as drugs

NH

OH

HO

HO

HO

OH

OH

OCOOH

HO

HO

HN

AcHN

OHH

NHH2N

Zanamivir (Relenza®)

COOEt

O

H2N

AcHN

oseltamivir (Tamiflu®)

NR

OH

HO

HO

acarbose(Glucobay®/Precose®/Prandase®)

voglibose(Basen®/AO-128/Volix)

R = CH2CH2OHmiglitol (Glyset®/Diastabol®)

R= n-BuN-butyldeoxynojirimicin(miglustat/Zavesca®)

HO OH

O

HO OH

OHO

HOO

HO

O

HO OH

NH

HO OH

OH3CHO

HO

HO

HO

Other industrial carbohydrate-based products

O

OHHO

HOO

alkyl polyglucosides (APG)x = 0.3-0.7; n = 1-5

OHHO

HO

OO

H

O

xn

surfactants50,000 t/a

OR1

OR2

OR3

O

O

OR5R6O

R7O

R8OO

R4O

Olestra (Olean®)R1...R8 = fatty acyl 6-8/H2-0

fat replacer (‘fatless’ fat)dioxin sequestrant

17

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

18

Oleic acid to value added chemicals from metathesis reactions

Terpenes• Pinene

– Isomerization: α-Pinene– Epoxidation of α-Pinene– Isomerization of α-Pinene Oxide– Hydration of α-Pinene: α-Terpineol– Dehydroisomerization

• Limonene– 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– Epoxidation of Camphene

• Citral– Aldol Condensations of Citral and Ketones– Baeyer-Villiger Oxidation: Melonal– Hydrogenation of Citral

Picture © Wikipedia

19

Some valuablecompounds that can be obtainedfrom αααα- and ββββ-

pinene

Vitamin A acetate:> 3,000 t/a

Lignins

• Production of dimethylsulfoxidefrom lignins

• Synthesis of vanillin

Picture © Craig Blacklock

20

The structure of lignins

• Main components (monomers) • Partial structure of a lignin polymer

OH

OCH3

CarbohydrateO

OCH3

CH2OH

O

CH

HCOH

CHOCHOH2C

O

CH3O

OCH3

HOH2C

O

HC

HC

OCH3

O

CH3O

HCCH

O

CHO

OH

CH2OH

O

CH

HC

HCCH

O

H2COH

CH3O

HCOHHC

O

CH2OH

OCH3

HOCH2

O

HCHC

OCH3

C

HC

OH [O-C]

CH2OH

OH

CH

HCOH

CH3O H2COH

CH3O

HC

HC

O

H2C

CH2

OH

CH

CH

O

O

CH2OH

O

CH

HCOH

OCH3

HO

OCH3

HCOH

HC

O

H2COH

CH3O

CH2OH

OH

HCCH

CH3O

O LigninCH3OO

CH2OHCH

HC

OH

OH

p-coumaryl alcohol

OOH

OH

coniferyl alcohol

OOH

O

OH

sinapyl alcohol

Vanilin from lignin

OH

OCH3

CHSO3-

OH

OCH3

CHO

[O]

alkaline oxidation

• 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 frompetrochemical sources (eugenol or guaiacol)

• Vanilin is also produced from waste sulfite liquors from the celluloseindustry by alkaline oxidation

• In the traditional process, >160 tons of caustic waste are produced for every ton of vanillin manufactured

21

DMSO from lignine

Lignosulfonates act as methylating agents

OH

OCH3

CHSO3-

HS-

OH

OH

CHSO3-

+ CH3S-OH

OCH3

CHSO3-

(CH3)2S (CH3)2SONO2

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, Wiley-

VCH, Weinheim.• F. Gunstone (2004): The chemistry of oils and fats: sources, composition, properties and uses. Wiley-

Interscience, New York.• F. Shahidi Ed. (2005): Bailey's industrial oil and fat products. Volumes 1-6, 6th Edition, Wiley-

Interscience, 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. Wiley-

Interscience, 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.

22

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, 1,4-pentanediol, 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 5-hydroxymethylfurfural. 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

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• kovacs@ovrisc.mdche.u-szeged.hu