Current Nonfood Industrial Uses Of Sugars

The current utilization of carbohydrates as a feedstock for the chemical industry—be it for bulk, commodity, intermediate, fine, or high-value-added speciality chemicals—is modest when considering their ready availability at low cost and the huge as yet unexploited potential. The examples currently realized on an industrial scale are outlined briefly.

2.2.1 Ethanol

With production of about 24 million tons (300 million hectoliters (hL)12), fermentation ethanol ("bioethanol") is the largest volume biobased chemical today. The principal organism for fermentation is Saccharomyces cerevisiae, an ascomyce-tous yeast that can grow on a wide variety carbohydrate feedstocks: sugar crops, and sugar-containing by-products, such as sugar cane, sugar beet, sorghum, molasses, and—after hydrolysis to glucose—starchy crops, such as corn, potatoes and grains, or cellulosic materials, for example, wood pulping sludges from pulp and paper mills.13a

The manufacturing costs are said to be roughly the same as those for its production from ethylene at a comparable plant size.13b The large growth in production of industrial-grade fermentation ethanol within recent years is less due to its use as a solvent and starting material for follow-up chemicals such as acet-aldehyde, ethyl esters (e.g., EtOAc), and ethers (Et2O)—these mostly result from ethylene-based processing lines—but from its high potential as a fuel additive. It is either directly admixed to standard gasoline to the extent of 5%, or indirectly in the form of ETBE (ethyl t-butyl ether) in proportions of up to 15%; however, a hefty government subsidy is required (repeal of the gasoline tax) to remain competitive. The growth opportunities for fuel-grade bioethanol are enormous and are predicted to increase substantially within the next five years.

2.2.2 Furfural

With an annual production of about 250 000 tons, furfural (2-furfuraldehyde) appears to be the only unsaturated large-volume organic chemical prepared from carbohydrate sources. The technical process involves exposure of agricultural or forestry wastes, that is, the hemicelluloses contained therein consisting up to 25% of d-xylose polysaccharides (xylosans), to aqueous acid and fairly high temperatures, the xylosans first being hydrolyzed, then undergoing acid-induced cyclodehydration.14 The chemistry of furfural is well developed, providing a host of versatile industrial chemicals by simple straightforward operations (Scheme 2.1): furfuryl alcohol (2) and its tetrahydro derivative 1 (hydrogenation), furfurylamine 3 (reductive amination), furoic acid 4 (oxidation), and furanacrylic acid 5 (Perkin reaction), or furyli-dene ketones 6 (aldol condensations). Furfural is also the key chemical for the commercial production of furan (through catalytic decarbonylation) and tetrahydro-furan (8) (hydrogenation), thereby providing a biomass-based alternative to its petrochemical production via dehydration of 1,4-butanediol.14 Additional importance of these furanic chemicals stems from their ring-cleavage chemistry,15 which has led to a variety of other established chemicals such as fumaric, maleic, and levulinic acid, the latter being a by-product of its production.16

Furan Resin Schema
OH

Scheme 2.1 Furanic commodity chemicals derived from pentosans in agricultural wastes (corn cobs, oat hulls, bagasse, wood chips).

Currently, the bulk of the furfural produced is used as a selective solvent in the refining of lubricating oil, and, together with furfurylalcohol in condensations with formaldehyde, phenol, acetone or urea to yield resins of complex, ill-defined structures, yet excellent thermosetting properties, most notably high corrosion resistance, low fire hazard, and extreme physical strength;14 they are extensively used in the foundry industry as cores for high-quality castings.

2.2.3 D-Sorbitol (;D-Glucitol)

Readily produced by hydrogenation of d-glucose,17 the main consumer of the sizable annual production of d-sorbitol (Table 2.1) is the food industry, primarily as a noncaloric sweetening agent; as a key intermediate for the production of ascorbic acid (vitamin C),18 it has important nonfood applications due to its moisture conditioning, softening, and plastifying properties. These entail its use in adhesives, paper, printing, textiles, cellulose-based foils, and pharmaceutical formulations.

Other nonfood applications of d-sorbitol result from etherification and poly-condensation reactions providing biodegradable polyetherpolyols used for soft polyurethane foams and melamine/formaldehyde or phenol resins. Sizable amounts of d-sorbitol also enter into the production of the sorbitan ester surfactants (cf. later in this chapter).

2.2.4 Lactic Acid ! Polylactic Acid (PLA)

Large amounts of d-glucose—in crude form as obtainable from corn, potatoes, or molasses by acid hydrolysis—enter industrial fermentation processes in the

Glucose-based feedstock (cornstarch, sucrose, molasses)

Fermentation with bacteria or fungi

Fermentation with bacteria or fungi

Pla Polykondensation

Ethyl lactate Polylactic acid

Scheme 2.2 Production of lactic acid and its uses.

Ethyl lactate Polylactic acid

Scheme 2.2 Production of lactic acid and its uses.

production of lactic acid (cf. Scheme 2.2), citric acid, and various amino acids, such as l-lysine or l-glutamic acid. While the major use of these products is in food and related industries, recent nonfood uses of lactic acid have made it a large-scale, organic commodity chemical. Most of it is subsequently polymerized via its cyclic dimer (lactide) to polylactic acid,19,20 a high molecular weight polyester.

Due to its high strength, polylactic acid (PLA) can be fabricated into fibers, films, and rods that are fully biodegradable (! lactic acid, CO2) and compostable, since they degrade within 45-60 days. Accordingly, PLA and copolymers of lactic and glycolic acid are of particular significance for food packaging and in agricultural or gardening applications; they are also highly suitable materials for surgical implants and sutures, as they are bioresorbable.

Since 1989, Cargill, has invested some $750 million to develop and commercialize polylactic acid (tradename: NatureWorks). Its Nebraska plant, with an annual capacity of 140,000 metric tons, opened in 2002.19-21 Thus, polylactides, combining favorable economics with green sustainability, are poised to compete in large-volume markets that are now the domain of thermoplastic polymers derived from petrochemical sources.

Another green development based on lactic acid is its ethyl ester (VertecTM) that has been marketed for applications in specialty coatings, inks, and straight-use cleaning because of their high performance and versatility.22 As a very benign solvent— green, readily biodegradable, and an excellent toxicology record it has the potential to displace various petrochemically based solvents such as acetone, dimethyl forma-mide (DMF), toluene, or N-methylpyrrolidone in industrial processes.

Green Chemistry Synthesis

APGs (x = 0.3-0.7; n = 2-5) Scheme 2.3 Synthesis of alkyl polyglucosides (APGs).

2.2.5 Sugar-Based Surfactants

The use of cheap, bulk-scale accessible sugars as the hydrophilic component, and fatty acids or fatty alcohol as the lipophilic part, yields nonionic surfactants, which are nontoxic, nonskin-irritating, and fully biodegradable. The industrially relevant surfactants of this type23 are fatty acid esters of sorbitol (sorbitan esters17) and of sucrose,24 fatty acid amides of 1-methylamino-1-deoxy-d-glucitol (NMGAs), and, most apparent in terms of volume produced, fatty alcohol glucosides, the so-called alkyl polyglucosides (APGs).25 The latter are produced

O^OH

Penicillin G

HOOC O

Cephalosporin C O

HOOC O

Cephalosporin C O

Kanamycin A

Ascorbic acid (Vitamin C)

0h ljk.OH

I MeHN I

0h ljk.OH

I MeHN I

Riboflavin (Vitamin B6)

Riboflavin (Vitamin B6)

Me2N

Ranitidine

,N02

"N^NHMe H

02N0

to 6no2

Isosorbide dinitrate

Isosorbide Fuel

0S02NH2

Topiramate

0S02NH2

Topiramate

Figure 2.3 Sugar-derived high-value-added products: antibiotics, vitamins, and pharmaceuticals.

by several companies—most notably by Cognis, with a capacity in the 50,000-t/y range—and are by far the most important nonionic surfactants. They represent fatty alcohol glucosides with an alcohol chain length normally between C8 and C14. Their industrial synthesis either comprises a direct acid-catalyzed Fischer glycosidation of glucose (in the form of a syrupy starch hydrolysate) or starch itself. The alternate process consists of two stages, the first being Fischer glycosidation with n-butanol to butyl glycosides, which are subsequently subjected to acid-promoted transacetalization.25

The resulting product mixtures (Scheme 2.3) contain mostly a-d-glucosides and are marketed as such. APGs are not skin-irritating, have good foaming properties, and are completely biodegradable; hence, they are widely used in hand dishwashing detergents and in formulations of shampoos, hair conditioners, and other personal-care products.24,25

2.2.6 Pharmaceuticals and Vitamins

Aside from the enormous amount of sugars, mostly glucose and sucrose, that flows into the fermentative production of amino and hydroxy acids (cf. Table 2.1)—a substantial part of which is for food use—a significant volume of these sugars enters into the fermentation processes of high-value-added products: antibiotics and vitamins, much too complex in their structures to be generated by chemical synthesis. Figure 2.3 lists a number of representative examples: penicillins and cephalosporins, with an estimated world production in the 75,000-t/y range, the aminoglycoside antibiotics of the kamamycin and spectinomycin type, or the recently optimized bioprocesses for the bulk-scale production of vitamins C and B6.

Some sugar-derived drugs obtained by chemical means have also achieved some importance, for example, ranitidine (Zantac®), an inhibitor of gastric acid secretion—one of the top 30 drugs based on sales26—isosorbide dinitrate, a coronary vasodilatator,27 or topiramate, a fructose-derived anticolvulsant drug with high antiepileptic efficacy.28

2.3 TOWARD FURTHER SUGAR-BASED CHEMICALS: POTENTIAL DEVELOPMENT LINES

Considering the large-scale, low-cost availability of the basic biomass-sugars listed in Table 2.1, their present nonfood use by the chemical industry is modest, that is, the huge feedstock potential of carbohydrates in general, and of low-molecular-weight sugars in particular, is largely untapped. In view of the necessity of the chemical industry to somehow effect the changeover from fossil raw materials to biofeedstocks—that is, primarily, to carbohydrates as these are more accessible from agricultural crops and waste materials than any other natural pro-ducts—their further development as industrial products is one of the major challenges of green chemistry. Thus, the fundamental basic and applied research objectives of the near future—hopefully, incorporated into the European Commission's 7th Framework Programme—must be to systematically improve existing methods for either chemical or enzymatic conversions of carbohydrates into industrially viable chemicals and materials, and to develop new ones.

The major directions that broad-scale exploratory research toward carbohydrate-based nonfood products will have to take, are—as far as conceivable today— outlined in the following for the four key sugars of biomass: the "royal carbohydrate"29 sucrose, d-glucose, d-fructose, and d-xylose.

2.3.1 Nonfood Valorization of Glucose: Potential Development Lines

2.3.1.1 Chemical Conversions. Although d-glucose is the component sugar of cellulose and starch, only the latter is the raw material for its commercial

'^Me Diacetonide Me

Me2CO/ ZnCl2

MeOH/H+

OH OH

OH OH SEt

Dithioacetal

D-Glucose

1. Ac20

3. Zn/HOAc

1.BzCl

3. Et2NH

Glucoside

Glucal

Hydroxyglucal

MeO"

MeO"

BzO,

BzO,

Scheme 2.4 Accessible, tautomerically fixed D-glucose derivatives with which to embark toward versatile building blocks.32

production.30 The chemistry of d-glucose is exceedingly well developed, its basic ensuing reactions going back to Emil Fischer, who in the 1890s, on the basis of oxidative and reductive conversions and through the synthesis of glucose by cya-nohydrin extension of arabinose, succeeded in figuring out its (relative) configuration.31 As a reducing sugar, d-glucose can form pyranoid, furanoid, and acyclic tautomers, so for ensuing straightforward reactions, the tautomeric form has to be fixed first (Scheme 2.4): isopropylidenation leads to the furanoid diacetonide, mercaptalization to an acyclic dithioacetal, pyranoid structures may be effectively generated in the form of glucosides, esters of glucal, and hydroxyglucal.32

Another simple, one-step entry from d-glucose to highly substituted furans involves their ZnCl2-mediated reaction with acetylacetone.33 Since only the first two sugar carbons of d-glucose contribute to the formation of the furan, a distinctly hydrophilic tetrahydroxybutyl side chain is produced; this chain can be shortened oxidatively to a dicarboxylic acid or a variety of other furanic building blocks (Scheme 2.5). By contrast, under mildly basic conditions d-glucose reacts with pentane-2,4-dione in an entirely different way, producing 2-C-glucosyl-propanone via C-addition and subsequent retroaldol-type elimination of acetate.34 Because this conversion can be performed with unprotected sugar and with simple reagents in aqueous solution, it fully complies with green and sustainable principles.1 The procedure is equally operable with other monosaccharides, and, thus, one of the cleanest and most efficient preparative entries into the area of C-glycosides, which as stable "mimics" of the usual O-glycosides, command major interest as glycosidase inhibitors.35

Despite the easy accessibility of these "entry products," and their fairly well-developed ensuing chemistry, their development toward industrial intermediates

Oxid.

co2h

Scheme 2.5 One-pot conversions of D-glucose into hydrophilic furans or, alternatively, into C-glucosides by reaction with acetylacetone.34

R'O" ^O

Figure 2.4 Enantiomerically pure six-carbon building blocks accessible from D-glucose via glucal (upper half) or hydroxyglucal esters (lower entries) as the key intermediates. All products require no more than 3 to 5 straightforward steps from D-glucose.37-46

is exceedingly modest. Nevertheless, to emphasize their potential toward industrial intermediates, be it as enantiopure building blocks for the synthesis of noncarbohydrate natural products36 or for agrochemicals and/or high-value added pharmaceuticals, a highly versatile array of dihydropyrans and dihydro-pyranones is given in Figure 2.4, all of which are derivable from d-glucose (via the glucal and hydroxyglucal esters) in no more than three to five straightforward steps. As in each of these products, at least two of the asymmetric centers of the d-glucose are retained, they are enantiomerically pure, and are thus ideal six-carbon building blocks for the synthesis of pharmaceuticals in enantiopure form.

Levoglucosenone, a bicyclic dihydropyranone, is accessible even more directly by vacuum pyrolysis of waste paper.47 Although the yield attainable is relatively low—levoglucosan is also formed, the amount depending on the exact conditions

(Scheme 2.6)—relatively large amounts can be amassed quickly; levoglucosenone has been used for the synthesis of a diverse variety of natural products in enantio-pure form.48

300-500°C

Cellulose (waste paper)

Cellulose (waste paper)

300-500°C

Levoglucosan (up to 10%)

Levoglucosan (up to 10%)

Levoglucosenone 3-4%

Scheme 2.6 High vacuum pyrolysis of cellulose.4

Kojic acid, a g-pyrone, is readily obtained from d-glucose, either enzymati-cally by Aspergillus oxyzae growing on steamed rice,49 chemically via pyranoid 3,2-enolones.36'50 A structurally similar a-pyrone can be effectively generated by oxidation of glucose to d-gluconic acid and acetylation.51 At present, both, are of little significance as six-carbon building blocks, despite a surprisingly effective route to cyclopentanoid products,52 which is surmised to have industrial potential.

D-Glucose

A. oryzae

C02H

Glucose-Derived Carboxylic Acids. There are several carboxylic acids derivable from d-glucose by chemical means that have broad potential as versatile intermediate chemicals for biorefinery platforms (Scheme 2.7): D-gluconic acid, the large quantity produced by oxidation of glucose53 (cf. Table 2.1) being used in the food, beverage, and pharmaceutical industries, yet also for removing calcareous and rust deposits from metals surfaces (due to its complexing properties) d-glucaric acid and levulinic acid.

D-Glucaric acid, directly produced by nitric oxidation of glucose or starch,54 is usually isolated as its 1,4-lactone. The technical barrier to its large-scale production mainly includes development of an efficient and selective oxidation technology to eliminate the need for nitric acid as the oxidant. Because it represents a tetrahydroxy-adipic acid, d-glucaric acid is of similar utility as adipic acid for the generation of polyesters and polyamides (see later in this chapter).

Levulinic acid and formic acid are end products of the acidic and thermal decomposition of lignocellulosic material, their multistep formation from the hexoses contained therein proceeding through hydroxymethylfurfural (HMF) as the key intermediate, while the hemicellulosic part, mostly xylans, produces furfural.55 A commercially viable fractionation technology for the specific

HO OH

O OH OH

O OH OH

HO OH

OH OH

D-Glucose

OH OH

OH OH O

OH OH O

D-Gluconic acid

Levulinic acid 5-Aminolevulinic acid

Scheme 2.7 Useful oxidation products of D-glucose.

acquisition of levulinic acid has been developed,56 rendering it an attractive option for a biorefinery platform chemical.57

Levulinic acid is a starting material for a large number of higher-value products, because it can be converted through established procedures into acrylic and succinic acids, pyrrolidines, diphenolic acid (which has the potential of replacing bisphenol A in the manufacture of polycarbonate resins), or 5-aminolevulinic acid used in agriculture as a herbicide and a growth-promoting factor for plants.

Hydrocarbons from D-Glucose? Being a six-carbon commodity graciously provided by Nature, albeit "overhydroxylated," a full deoxygenation of glucose (or other hexoses) formally leads to n-hexane, which is usable as a liquid fuel. If such a process could be made practically feasible—this author is well aware that some will say "Never"—it would certainly exceed glucose-derived ethanol as a biofuel (additive), inasmuch as fermentation cuts the six-carbon chain into ethanol and CO2, while deoxygenation implies full atom economy by retaining it.

Recent investigations aimed at establishing such a deoxygenation process have met with some success, yet are admittedly far from industrial implementation. Sorbi-tol, for example, readily accessible from glucose through catalytic hydrogenation,17 can be tailored to produce a mixture of alkanes consisting primarily of butane, pentane, and hexane, by exposing an aqueous solution to a metal (Pt or Pd) and solid acid catalysts (SiO2-Al2O3) and hydrogen at 225°C.58 The process is complex, as it not only entails a series of dehydrations and hydrogenations to eventually provide n-hexane, but also dehydrogenations and C—C fissions to produce pentane and butane.

C4-C6 Alkanes are highly volatile and, hence, of low value as a transportation fuel or a fuel additive. Since high-quality fuels require the generation of liquid hydrocarbons, the fructose-derived HMF and acetone have been converted into their mono- (C9) and bis-aldols (C15), which on SiO2-Al2O3/Pt-catalyzed dehy-dration/hydrogenation produce C9-C15 alkanes (Scheme 2.8).59 A major drawback of this approach, however, is the fact that HMF, de facto, is a fructose-derived product,60 and is not producible in an industrially viable price frame at present (vide infra, Section 2.3.2).

2.3.1.2 Valorization of D-Glucose Through Microbial Conversions. Some experts predict that biotechnology will produce up to 20% of the industrial chemicals by 2010—from currently 5%.61,62 Undoubtedly, such an increase will receive its major thrust from the various genetically engineered bioprocesses currently in industrial pipelines, most notably those that involve the bioconversion of d-glucose—Nature's principal sugar for essentially any biotransformation—into industrially important C3-C5-carboxylic acids apart from those already exploited (cf. Table 2.1) or into alcohols other than ethanol.63

Intense research and development efforts currently appear to go into the following chemicals:

3-hydroxypropionic acid

1,4-diacids (malic, fumaric, succinic)

itaconic acid

1,3- and 1,2-propanediol of which the carboxylic acids—currently petroleum-based bulk commodities—are on the list of the 12 future sugar-derived platform chemicals57 of the U.S. Department of Energy. If low-cost d-glucose-based fermentation routes can be developed and implemented on an industrial scale, there is a good chance of their production process being replaced along petrochemical channels.

D-Glucose

OH OH OH

D-Sorbitol

OH OH OH

D-Sorbitol

Si02-Al203 225°C

OH OH OH

OH OH OH

OH OH OH

OH OH OH

HO OH O

HMF/Acetone aldol Pt/H2

C9-Alkanes n-Hexane

Scheme 2.8 Effectuation of the deoxygenation of D-glucose (or other sugars) to hydrocarbons.58'59

3-Hydroxypropionic Acid (3-HPA). Like the structurally isomeric lactic acid, 3-HPA constitutes a three-carbon building block with the potential of becoming a key intermediate for a variety of high-volume chemicals: malonic and acrylic acids, methacrylate, acrylonitrile, 1,3-propanediol, and so forth.57b Thus, Cargill is developing a low-cost fermentation route by metabolic engineering of the microbial biocatalyst that produces 3-HPA under anaerobic conditions,6^ yet it will take another one or two years for the process to reach commercial viability.6413

Lactic acid (LA) 3-Hydroxypropionic acid

(2-Hydroxypropionic acid) (3-HPA)

Unlike a product such as lactic acid, another of 3-HPA's appeals is that, at present, it is not manufactured commercially, either by chemical or biological means.

1,4-Diacids. The microbial generation of malic, fumaric, and succinic acid essentially implies Krebs cycle pathway engineering of biocatalytic organisms to overproduce oxaloacetate as the primary four-carbon diacid that subsequently undergoes reduction and dehydration processes (Scheme 2.9). The use of these four-carbon diacids as intermediate chemicals and the state of their desirable microbial production is briefly outlined.

The major portion of malic acid currently produced at an approximate 10,000 t/y is racemic, because it originates from petrochemically produced fumaric acid. The l-form can also be generated from fumaric acid by its hydration with immobilized cells of Brevibacterium or Corynebacterium.

Fumaric acid, a metabolite of many fungi, lichens moss and some plants, and mainly used as the diacid component in alkyd resins,65 is produced commercially to some extent by fermentation of glucose in Rhizopus arrhizus,66 yet productivity improvements appear essential for the product to be an option for replacing its petrochemical production by catalytic isomerization of maleic acid.

Succinic acid is used in producing food and pharmaceutical products, surfactants and detergents, biodegradable solvents and plastics, and ingredients to stimulate animal and plant growth. Although it is a common metabolite formed by plants, animals, and microorganisms, its current commercial production of 15,000 t/y is from petroleum, that is, by hydrogenation of fumaric or maleic acid. The major technical hurdles for succinic acid as a green, renewable, bulk-scale commodity chemical—1,4-butanediol, THF, g-butyrolactone, or pyrrolidones are industrially relevant follow-up products—include the development of a very low-cost fermentation route from sugar feedstocks. Currently available anaerobic fermentations of glucose (Scheme 2.9) include a genetically cloned form of Aspergillus succinoproducens, an engineered E. coli strain developed by DOE laboratories,57c and a number of others67—processes that are currently under active development. Production costs are to be brought to or below $ 0.25/pound in order to match those via petrochemical channels.57c

d-Glucose

Pyruvate carboxylase Pyruvic acid C02

Malate dehydrogenase

Oxaloacetic acid

Oxaloacetic acid c

NADH NAD+

Polyethylene Terephthalate Glycolysis

Fumarase

Succinic acid

Scheme 2.9 Glycolytic pathway leading to the L-malic, fumaric, and succinic acids.

Succinic acid

Fumarase

NADH NAD+

O OH

l-Malic acid

O OH

l-Malic acid

Scheme 2.9 Glycolytic pathway leading to the L-malic, fumaric, and succinic acids.

Itaconic Acid. Structurally an a-substituted methacrylic acid, itaconic acid constitutes a C5 building block with significant market opportunities. It is currently produced via fungal fermentation at about 10,000 t/a68 and mainly used as a specialty comonomer in acrylic or methacrylic resins, as incorporation of small amounts of itaconic acid into polyacrylonitrile significantly improve their dyeability.

Itaconic acid O

To become a commodity chemical, though, productivity improvements with the currently used fungi Aspergillus terrous and Aspergillus itaconicus are required, and promising ameliorations appear to be in the making.69 To be competitive to analogous commodities, the crucial production price of about 0.25 $/ 1b has to be reached57d—a significant technical challenge still to be solved.

1,3-Propanediol. Both the diol and the dicarboxylic acid components of poly-trimethylene-terephthalate, a high performance polyester fiber with extensive applications in textile apparel and carpeting, are currently manufactured from petrochemical raw materials.

Sorona® (Dupont70) Corterra® (Shell71)

Poly-trimethylene-terephtalate

For the polyester's 1,3-propanediol portion, however, biobased alternatives have been developed, relying on microbial conversions of glycerol,72 a by-product of biodiesel production, or of corn-derived glucose.73 For the latter conversion, DuPont has developed a biocatalyst, engineered by incorporating genes from baker's yeast and Klebsiella pneumoniae into E. coli, which efficiently converts corn-derived glucose in 1,3-propanediol.70,73 The bioprocess, implemented on an industrial scale in a Tennessee manufacturing plant by a DuPont/Tate & Lyle joint venture, provided the first bulk quantities in November 2006.74

Fermentation

1,2-Propanediol. In its racemic form, 1,2-propanediol is a petroleum-based highvolume chemical with an annual production of over 500,000 t, mostly used to manufacture the unsaturated polyester resins, yet also featuring excellent antifreeze properties. Enantiomerically pure (R)-1,2-propanediol accumulates along two different pathways via DAHP (3-deoxy-d-arabino-heptulosonic acid 7-phosphate) and methylglyoxal, which then is reduced with either hydroxyacetone or lactaldehyde as the intermediates. Both routes have been examined for their microbial production from glucose by means of genetically engineered biocatalysts, obtained by expressing glycerol dehydrogenase genes or by overexpressing the methylglyoxal synthase gene in E. coli.75 Another approach implies inoculating silos with chopped whole-crop maize with Lactobacillus buchneri; after storing for four months, yields of 50 g/kg were reported.76 Thus, prospects for elaborating an economically sound bioprocess look promising.

2.3.2 D-Fructose: Potentials for Nonfood Uses

The substantial amounts of this ketohexose are mainly prepared by base-catalyzed isomerization of starch-derived glucose,77 yet may also are generated by hydrolysis of inulin, a fructooligosaccharide.78 An aqueous solution of fructose—consisting of a mixture of all four cyclic tautomers (Figure 2.5), of which only the b-d-pyranose (b-p) form present to about 73% at room temperature is sweet79— about 1.5 times sweeter than an equimolar solution of sucrose; hence, it is widely used as a sweetener for beverages ("high fructose syrup").

The nonfood utilization of fructose is modest—not surprising, since its basic chemistry is more capricious and considerably less developed than that of glucose.79a

Pyranose Furanose

Figure 2.5 Forms of D-fructose in solution. In water, the major conformers are the b-pyranose (b-p; 73% at 25°C) and b-furanose (b-f, 20%) forms.79 On crystallization in water, D-fructose exclusively adopts the 2C5 chair conformation, as shown by X-ray analysis.80

Chair Form Frutose

BzO 1

p-n-Fructose

Hi 0H

Fructose Diacetonide
Me

BzO 1

Br p-n-Fructose

Me M

Scheme 2.10 Readily accessible fructose derivatives fixed in pyranoid form. Key for conditions: A: Glycol/H+, 74%81 B: BzCl/Pyr., -10°C ! HBr, 63%82 C: Zn/MIM, 90%83 D: Nal/acetone, then 140°C in xylene, 53%84 E: Me2CO/cat. H2SO4, 58%85 F: Me2Co/ > 5% H2SO|6 G: acetylacetone, aq. NaHCO3, 85°C, 35%.87

Nevertheless, there are various "entry reactions" into simple pyranoid derivatives (Scheme 2.10) with which to exploit their industrial application potential.

Equally simple entries—in fact, one-pot reactions each—lead from D-fructose to N-heterocycles of the imidazol, pyrrole, and pyridine type (Scheme 2.11), all of which, due to their hydrophilic substitution patterns, are considered useful building blocks to pharmaceuticals.

By far the highest industrial potential for a fructose-based compound is to be attributed to HMF, which has been termed "a key substance between carbohydrate chemistry and mineral-oil-based industrial organic chemistry."92 Like the bulk-scale commodities hexamethylenediamine and adipic acid, HMF represents a six-carbon compound with broad industrial application profiles. It is readily accessible from fructose or inulin hydrolysates by acid-induced elimination of three moles of water.60 Even a pilot-plant-size process has been elaborated.92

HMF as such has been used for the manufacture of special phenolic resins, as acid catalysis induces its aldehyde and hydroxymethyl group to react with phenol.98

oh ch2o/nh3

cu(OH)2

oh ch2o/nh3

cu(OH)2

Organic Pt02 Catalyst
oh oh

Scheme 2.11 Versatile N-heterocyclic building blocks derivable from fructose in one-pot reactions;88-91 the hydrophilic side chain can be oxidatively shortened to elaborate aldehyde or carboxylic acid functions.

HO

F\

OH

J

HO OH

OH OH

OH OH

D-Fructose

(Inulin)

J

r\

.OH

r

o

[f

HO

HO NH2

!T\

H

r^)

f

un 1 HU HMF

_>

HO NH2

Scheme 2.12 Versatile intermediate chemicals from HMF.

Of equally high industrial potential as intermediate chemicals are the various HMF-derived products for which well-worked-out, large-scale adaptable production protocols are available. Of these, the 5-hydroxymethyl-furoic acid, the 2,5-dicar-boxylic acid, the 1,6-diamine, and the respective 1,6-diol (framed in Scheme 2.12) are the most versatile intermediate chemicals of high industrial potential, as they represent six-carbon monomers that could replace adipic acid, alkyldiols, or hexamethy-lenediamine in the production of polyamides and polyesters.

Polyester Polyamides

Polyester Polyamides

Hydroxymethyl Polykondensation Furan
Figure 2.6 Furanoic polyesters and polyamides of potential industrial significance.

Indeed, an impressive series of furanic polyesters and polyamides has been prepared15 in which the furan-dicarboxylic acid replaces terephthalic and isophthalic acid in the present industrial products (cf. Figure 2.6), yet none has proved economically competitive to existing products. Thus, as of now, HMF, is not produced on an industrial scale. A tentative assessment of its economics as compared to petrochemical raw materials clearly unfolds the reasons underlying: ton prices of naphtha and ethylene are in the 150-400 E range, that of anilin (500 E/t), and of fructose in particular (^1000 E/t) are substantially higher, entailing an HMF-marketing price of at least 2500 E/t—too expensive at present for a bulk-scale industrial product. Accordingly, as long as the economic situation favors fossil raw materials, applications of HMF lie in high-value-added products, such as pharmaceuticals or special niche materials.

Guide to Alternative Fuels

Guide to Alternative Fuels

Your Alternative Fuel Solution for Saving Money, Reducing Oil Dependency, and Helping the Planet. Ethanol is an alternative to gasoline. The use of ethanol has been demonstrated to reduce greenhouse emissions slightly as compared to gasoline. Through this ebook, you are going to learn what you will need to know why choosing an alternative fuel may benefit you and your future.

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Responses

  • ali anani
    This is a very interesting idea for forming sugar-based industrial clusters. The options are wide. I wish to see a brief description of the feasibility of the promising applications and the determining cost factors to encourage investments in the field of green chemistry
    8 years ago
  • aedan
    Does fructose fischer conformation?
    8 years ago
  • Regina
    How does fructose react with phenol?
    8 years ago
  • michael
    Can alkyl polyglycosides be made from biomass?
    8 years ago
  • ATSO
    What is sorbitol industrially produced from?
    8 years ago

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