Green Chemistry Application for

Sustainable Development

Lecture 5

1
 Principle 9 - Catalysis,
catalytic reagents

Catalytic reagents with great selectivity can

be superior to stoichiometric reagents.
New catalysts and more emphasis on
catalytic processes is the future of green
chemistry techniques

2
Since the 1990s, the scientific community has progressively changed its approach
toward dealing with regulations for environmental protection. This evolution in the
chemical industries has led to the development of green chemistry.

In the last decade, green chemistry has been widely recognized and accepted as a
new means for sustainable development.

As the name suggests, green chemistry is a scientific approach that is inherently

safer than the old-fashioned cleanup chemistry, which, prior to the 1990s, was used
to meet environmental protection laws.

Industries are often forced to pay heavy prices to meet with the standards set by the
pollution regulatory boards while using the traditional methods of treating or recycling
waste.

Also, with growing environmental problems, law-making boards are now looking
more critically at the possible hazardous effects of a larger number of chemical
substances.

The growing importance now given to green chemistry can be attributed to the ability
of this approach to bridge eco-efficiency and economic growth.

3
 Catalysis and Green Chemistry
Catalysis plays a major role in making industrial processes more efficient and
economically profitable. This can be quite obviously attributed to three general
characteristics of catalysts:

► Catalytic reagents reduce the energy of the transition state, thereby reducing the
energy input required for a process.

► Catalysts are required in small quantities. In the case of biocatalysts, the number
of catalysts (generally enzymes) needed compared to the quantity of reactants is
very low.

►The regeneration and reversibility of catalysts are good for green processes.

A catalyst: A material which changes (usually increases) the rate of

attainment of chemical equilibrium without itself being changed or
consumed in the process.

Today it is estimated that some 90% of the chemicals used have, at

some stage in their manufacture, come into contact with a catalyst.
4
 By increasing the rate of
attainment of equilibrium through
lowering the activation energy,
catalysts reduce the energy
requirement of a process and
therefore can be considered to be
inherently green.

Activation energy for catalysed and

uncatalysed ammonia synthesis

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 Atom-economy (or efficiency) (AE) factor with catalyst

A.E. = 42%
Jones oxidation of secondary alcohol

Atom-economical oxidation of secondary alcohol A.E. = 87%

A.E. = 100%

Macrolactone synthesis with high atom-efficiency (Trost et.1998)

6
 Mobil/Badger cumene process

Zeolites and clay-catalyzed, high-AE reactions

The use of zeolites in the manufacture of cumene is of immense importance. About

7 million tons of cumene are produced annually worldwide.

The earlier-used process involved alkylation of benzene over a solid phosphoric

acid or an aluminum chloride catalyst. Both catalysts are toxic in nature.
The Mobil/Badger cumene process (Mobil Technology Co., 1997) uses the less
toxic carozine zeolite catalyst. In addition, it also generates less waste and requires
less energy than the earlier catalysts, thus simultaneously satisfying various
conditions of green chemistry.
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 Catalyst Types
Catalysts are commonly divided into two basic types, heterogeneous and
homogeneous, depending on their state relative to the reaction medium.

Heterogeneous catalysts referred to as surface catalysts or contact catalysts

owing to their mode of action, are in a different phase to the reaction medium.
Heterogeneous catalysts are widely used industrially.
In most cases the catalyst is a solid with the reactants being in the gaseous phase.
The actual reaction takes place on the surface of the catalyst, which may be the
external surface or, more effectively, a surface within internal pores of the solid.

Homogeneous catalysts are in the same phase as the substrate and are
uniformly distributed. In almost all cases the reaction takes place within the liquid
phase, the catalyst being dissolved in the reaction medium.

In general, the ultimate goal of many researchers working in this field is to combine
the best characteristics of both types of catalyst. One of the main aims of this work is
to combine the fast rates and high selectivities of homogeneous catalysts with the
ease of recovery and recycle of heterogeneous catalysts. In the majority of cases (but
not all) this results in attempts to heterogenize a homogeneous catalyst.
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 Comparison of heterogeneous and homogeneous catalysts

Heterogeneous
Usually distinct solid phase
Readily separated
Readily regenerated and recycled
Rates not usually as
homogeneous
May be diffusion limited
Quite sensitive to poisons
Lower selectivity
Long service life
Often high-energy process
Poor mechanistic understanding
Homogeneous
Same phase as reaction medium
Often difficult to separate
Expensive/difficult to recycle
fast as Often very high rates
Not diffusion controlled
Usually robust to poisons
High selectivity
Short service life
Often takes place under mild
conditions
Often mechanism well understood

9
Conclusions

► Catalysts play a significant role in green chemistry by decreasing energy

requirements, increasing selectivity, and permitting the use of less
hazardous reaction conditions.

► The central role these catalysts play in directing the course of a reaction,
thereby minimizing or eliminating the formation of side products, cannot be
disputed.

► Hence, catalysis - or rather, designed catalysis - is the mainstay of green

chemical practices.

10
 Biocatalysis

Biological reagents are used in chemistry both for the production of defined products
(biocatalysis) and for the removal of specific toxic materials by conversion to benign
products (biodegradation).

Biocatalysis - the use of a biological system to catalyse the conversion of a

single material (the substrate) to a defined product - has a long history in organic
chemistry, and specific biocatalytic steps have been used in the industrial production
of both bulk and fine chemicals for many years.

The ability of enzymes to catalyse organic reactions in the moderate pH range of 4 –

9 at reasonable temperatures (10 – 50°C) and without extremes of pressure or the
addition of metals can provide an environmentally acceptable method of performing
many reactions that otherwise may require highly acidic or alkaline environments,
high energy input for heating or toxic metal catalysts.

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The largest scale industrial biotransformation is currently the conversion of glucose to
fructose by the enzyme glucose isomerase, which accounts for the production of 10
million tones/year of high-fructose syrup.

Conversion of glucose to
fructose by glucose
isomerase

The food industry also uses the enzyme galactosidase for the conversion of lactose
into glucose and galactose, a key process in the production of low-lactose milk
products on a large scale, with up to 250000L of milk being processed on a daily
basis.

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In the pharmaceutical industry, the largest scale biocatalytic process is the
conversion of the fermentation product penicillin G into 6-aminopenicillanic acid by
the enzyme penicillin acylase. The latter is used as the starting point for the
production of chemically modified penicillins, and is produced on scales
approaching 16000 tonnes/year.
This biotransformation is carried out under neutral conditions and without the need
for elevated temperatures; the chemical process that it superseded required the use
of low temperatures, anhydrous conditions and organic solvent.

Conversion of penicillin G (Pen-G) to 6-aminopenicillanic acid

(6- APA) by penicillin acylase

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 Aspects of enzyme catalysis relevant to green chemistry

Property Green chemistry relevance

Fast reactions due to correct catalyst Faster throughput
orientation
Orientation of site gives high Possibility for asymmetric synthesis
stereospecificity
High degree of substrate specificity due High degree of selectivity
to limited flexibility of active site
Water soluble Opportunity for aqueous-phase
reactions
Naturally occurring Non-toxic, low hazard catalysts
Natural operation under conditions Non-toxic, low hazard catalysts
found in body Energy-efficient reactions under
moderate conditions of pH,
temperature, etc.
Possibility for tandem reactions when Possibility for carrying out sequential
using whole organisms one-pot syntheses
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General Characteristics of Enzymatic and Chemical Reactions

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 Pharmaceuticals industry

Production of cortisone and related

anti-inflammatory steroids has relied
on a biocatalytic hydroxylation
reaction to introduce an oxygen atom
at carbon-11 of a suitable precursor
such as progesterone using an
Arthrobacter species.

Pharmaceutical natural products –

the anti-cancer drugs vinblastine and
vincristine obtained from cell cultures
of Catharanthus roseus.

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 Flavour and fragrance compounds

Fungus Pycnoporus cinnabarinus, a

biocatalyst for the conversion of vanillic
acid into vanillin at levels of over 1g/L.

The slimming aid and dietary supplement L-carnitine is produced on a multi-

hundred-tonne scale annually. One route for its preparation is the hydroxylation of
g-butyrobetaine using a mutant bacterial. Strain in which the enzymatic pathway for
degradation of the production is absent. This process has been optimised by the
Lonza group and production levels of over 100g/L are attainable.

Another large-scale application—the production of the artificial sweetener

aspartame—was developed by the Tosoh Corporation in Japan and uses the
isolated enzyme thermolysin to couple suitably protected aspartate and
phenylalanine precursors. This process has been optimised to operate with racemic
phenylalanine methyl ester, the coupling reaction being specific for the natural (L)
isomer.

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 Carbohydrates

The manufacture of vitamin C - the original process combines chemical and

biocatalytic steps, the latter being an oxidation of D-sorbitol to L-sorbose by
Acetobacter suboxydans.

Recent developments in metabolic pathway engineering of Erwinia herbicola

bacteria have produced a strain capable of conversion of D-glucose into 2-
ketogulonic acid (the immediate precursor for vitamin C) at levels of 120g/L in a
yield greater that 60% and in an improvement on the original process the
production of L-sorbose from D-sorbitol using Gluconobacter oxydans has been
optimised at levels of 200 g/L.
The large-scale production of
The formation of glycosidic derivatives glycosyl transferase enzymes for
produced stereoselectively from maltose similar transformations has been
and menthol by biocatalysis using the food- developed using a recombinant
approved microorganism Xanthomonas over-expression system in
campestris. Escherichia coli.

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 Polymers
Biocatalytic polymer formation by whole cell systems is limited to the production of
biopolymers such as the poly(hydroxyalkanoates) typified by poly(3-hydroxybutyrate-
co-3-hydroxyvalerate), produced by Ralstonia eutropha.

Isolated lipase preparations from Candida antarctica or Pseudomonas cepacia

are used most frequently for the polymerisation of lactones.

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Routes for the formation
of polyesters by catalysis
using lipase enzymes

Enzymic polymerisation
of phenols

20
 Biocatalysis in waste treatment
The toxicity of phenol and phenolic derivatives in industrial wastewaters found in
wastes from oil refineries and paper processing plants was found at concentrations
up to 1.5 g/L. Phenol can be removed effectively from aqueous solution by
biocatalytic oxidation using immobilised cells of Pseudomonas putida that can
tolerate and oxidise phenol at levels up to 1.5 g/L and similar concentrations are
completely mineralised by Candida tropicalis or Alcaligenes faecalis in the
presence of high salt concentrations.

Cyanide ion is a potent inhibitor of oxidative metabolism and its removal from
effluents is an essential part of many waste treatment protocols, particularly in the
mining and metal processing industries. Immobilised cells of Pseudomonas putida
have been reported to convert cyanide ion at up to 120mM aqueous concentration
into carbon dioxide and ammonia: the same cells also were able to degrade cyanate
and thiocyanate ions, the former to ammonia and carbon dioxide and the latter to
ammonia, carbon dioxide and an unspecified sulfur containing product.

The activities of haloalkane dehalogenase enzymes in microorganisms such as

Rhodococcus species and Xanthobacter autotrophicus (a bacterium capable of
growing on 1,2-dichloroethane as a sole source of carbon) can be exploited for the
bioremediation of soils contaminated with non-aromatic halocompounds.
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 Removal of phenols
from water via
oxidation to ortho-
quinones

Metabolism of
metolachlor
by Cunninghamella
elegans

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 Applications of biocatalysis in industry

Compounds, Types of Transformations/Reactions

Transformed/ Synthesized
Steroids and sterols Hydroxylation, dehydrogenation, side chain
degradation, hydrolysis, peroxidation, reduction,
isomerization and conjugation
Semisynthetic Synthesis of penicillins and cephalosporins (acylases),
antibiotics modification of carbapenem side chain
Organic acids Hydration of fumaric acid, oxidation of alkenes,
oxidation of isobutyric acid, reduction of 3-chloroacetic
acid ester, aminolysis of histidine
Sugars Isomerization of glucose, hydrolysis of starch,
hydrolysis of cellulose, hydrolysis of sucrose
Peptides and proteins Synthesis of plastin, semisynthesis of human insulin,
synthesis of aspartame
Commodity chemicals Synthesis of alkene oxides, ketones, aldehydes,
pyrogallol, and amides
Nucleic acid-related trans-N-ribosylation, phosphorylation of nucleosides,
compounds synthesis of nucleotides, synthesis of co-enzymes,
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nucleosidylation of L-methionine and L-homocysteine
Conclusions

► Although replacement of chemical processes by biological catalysts usually

results in a more sustainable process, the costs associated with the use of a
biocatalyst, arising for example from short catalyst lifetimes and the need to
invest in specialised equipment, often can exceed those of the traditional
chemical-based operation.

► The success of industrial biocatalysis has been largely in those areas for
which the chemical alternative is either not available (e.g. glucose–fructose
isomerisation and corticosteroid production) or simply not viable on the scales
required (e.g. penicillin production).

► The number of microorganisms that have been examined systematically for

their potential in this area represent only a small fraction of those available,
and this, together with the ability of microbiologists to produce tailor-made
catalysts by genetic manipulation, leaves the field open for the discovery of
new and useful biocatalysts for future application in a wider range of chemical
processes than has been possible up to now.

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Principle 10 – Design products which
degrade easily

Green Chemistry aims at designing products

so that at the end of their useful life to break
down into innocuous materials and do not
persist in the environment

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Green chemistry practitioners aspire to optimize the commercial function of a
chemical while minimizing its hazard and risk. Hazard, the capability to cause harm,
is an inherent characteristic arising, like function, from a chemical’s stereochemistry
(the content and arrangement of atoms).

Green chemistry principles 3, 4, 5 and 12 guide designers to reduce the hazards of

chemicals. Principle 10 guides the design of products that degrade after their
commercial function in order to reduce risk or the probability of harm
occurring.

Degradation can eliminate significant exposure, thereby minimizing risk regardless of

the hazard of the chemical involved.

Exposure to persistent chemicals can be significant as a result of global dispersion

enabled by properties such as volatility or sorption to particles and partitioning into
organisms based on properties such as fat solubility. Regulators have established
criteria (half-lives in water, soil, air) that define persistence within frameworks used to
identify chemicals as PBT (Persistent, Bioaccumulative, Toxic).

A green chemistry objective is to design out molecular features responsible for

hazardous characteristics and risk. Trade-offs, or alternative approaches, must
be evaluated when the molecular features to be designed in for commercial
function overlap with those to be designed out to reduce hazard and risk. 26
Prediction methods that can guide the design of molecular architecture expected to
degrade include rules of thumb linking structural features to degradability or
persistence, databases of existing knowledge, models that evaluate biodegradability
or PBT attributes, and experimental testing. All of these tools can be adapted to
individual chemical sectors and specific objectives.

In the early 1960’s, industry transitioned from non-biodegradable branched

surfactants, which caused extensive foaming and other health problems in surface
waters receiving WWTP (wastewater treatment plants) effluent, to biodegradable
linear alkyl benzene sulfonate based detergents – an approach to innovative design
that continues today.

Predictive decision-making tools must provide confidence about hazard and risk in a
way that is aligned with the timing and magnitude of development decisions, and
most importantly, while there is still flexibility to alter a molecular design or product
formulation.

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Among the best known materials that are being produced intentionally for a limited
life are degradable plastics.

As with so many technological advances, plastics bring not just enormous benefits to
society but also grave threats if misused:
- they allow us to make goods that would otherwise be impossible to fabricate
economically, goods that we rely on in everyday life;
- have two great environmental handicaps:
1. The vast majority are made from non-renewable fossil fuels, oil and
natural gas;
2.Their desirable virtues of strength, inertness to chemicals, microorganisms
and light also make them difficult to dispose of in an eco-friendly way.

With natural polymers, specific enzymes have developed over billions of years to aid
rapid degradation; for most of the plastics developed over the last 80 years, no such
enzymes exist.

Making a plastic from a renewable resource does not necessarily mean that its
disposal will be eco-friendly.
Poly(ethene) could be made from biomass via ethanol and ethene but it is still very
difficult to degrade.
Polycaprolactone is a biodegradable plastic but is produced via cyclohexanone, itself
derived from benzene (whose manufacture is based on oil). 28
 Degradable plastics from renewable resources
The poly(hydroxyalkanoates), PHAs, are now much used. They are made from
renewable materials and are readily degradable. PHAs are polyesters which are
produced by bacteria grown on certain substrates from which nutrients such as
nitrogen are withheld. The bacteria are encouraged to produce an energy store for
later use, similar to the way that plants produce starches. Considerable work is being
devoted to producing genetically-engineered E.coli to grow PHAs in this manner.

Amongst these polyesters, poly(hydroxybutanoate), PHB, is the best known. It is

produced by fermentation of glucose solutions (produced from starch by hydrolysis)
to which propanoic acid has been added. Sources of nitrogen as a nutrient are
withheld. The bacterium is Ralstonia metallidurans.

Those polymers is used to wrap foods, coatings for paper and cardboard, kitchen
ware (cups, saucers, plates), and many medical uses, including sutures, gauzes
and coatings for medicines. 29
Another degradable polyester is poly(2-hydroxypropanoic acid) (polylactic acid,
PLA), produced from 2-hydroxypropanoic acid (lactic acid).
The lactic acid, traditionally made from ethanal (acetaldehyde) and hydrogen
cyanide, is now being increasingly produced by an alternative method, the
fermentation of sugars from maize (corn syrup) and cane sugar (molasses) using the
lactobacillus bacterium.

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31
Co-polymers of PLA with poly(hydroxyethanoic acid) (polyglycolic acid), PGA
have found considerable use in surgery. Threads of the co-polymer, which is a block
co-polymer are used for stitching internal wounds and are degraded back to their
parent monomers within 90 days after surgery. The acids are biocompatible with the
body.

Some polymers based on starch are derived from renewable resources and are
readily degradable. The starch used is from corn (maize). This contains a high
proportion of amylose. The starch is treated with epoxypropane (propylene oxide)
which reacts with some of the hydroxyl groups in the amylose. The resulting
polymer can be used in place of polymers such as poly(propene) and
poly(chloroethene), PVC. It is being increasingly used for bags, packaging for
biscuits and chocolates.

A polymer derived from

starch can be
degraded. The polymer is
also composted readily by
microorganisms in the soil.

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 Degradable plastics from fossil fuels

These polymers are synthetic biodegradable polymers, that is polymers which are
not made by biological processes, but which will still degrade.

One type are the synthetic polymers such as poly(ethene) which have starch
granules encapsulated in the structures, the amount varying from 5-50 %. These
granules are degraded by bacteria and the tiny fragments of poly(ethene) produced
degrade at a faster rate than poly(ethene) without the starch, although more slowly
than biopolymers.

Another important example of a fast degrading polymer derived from a

petrochemical source is poly(ethenyl alcohol), known better by its older,
unsystematic name, polyvinyl alcohol, PVA. Over 1 million tonnes are made
annually worldwide. PVA is a readily degradable water-soluble polymer and among
its uses are as an adhesive (paper, fabrics, leather) and for coating paper and
paperboard. It is also used as a thickener in a wide range of liquids including
paints, glues and hairsprays.

Partially hydrolyzed PVA, containing 1-3 % ethanoate groups, reacts with butanal to
form PVB - polyvinyl butyral which has very good optical clarity, is tough and bonds
strongly to glass. PVB is used extensively as the middle layer in laminated (safety)
glass used, for example, in cars. 33
 Photodegradable polymers
These are polymers whose disintegration is initiated by sunlight.

A strategy to degrade more quickly is to add a compound to the plastic, known as a

prodegradant additive. Some are known as Totally Degradable Plastic Additives,
TDPAs. They are added to conventional polymers such as poly(ethene) and
poly(propene) and used in shopping bags shopping and food wrapping.

The polymers are degraded within a few months in a conventional compost facility,
and have better mechanical properties than the starch-filled polymers.

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 Alkylbenzene sulfonates
The most common of the synthetic anionic surfactants are based on the straight
chain alkylbenzene sulfonates. The alkylbenzene varies in average molecular mass,
depending upon the starting materials and catalyst used and is often a mixture in
which the length of the alkyl side chain varies between 10 and 14 carbon atoms.

Alkylbenzene
(detergent alkylate)

By law, in most countries today, the surfactant must have side chains which are not
branched so they degrade more rapidly.

When heated in excess ethene, straight chain alkenes, with the double bond at the
end of the chain (an a-alkene), are produced:

The mixture is then separated into fractions by distillation, the fraction of alkenes
containing 10 to 14 carbon atoms being used to make the surfactants.
These are used together with other surfactants in powder and liquid laundry 35
detergents such as Ariel, Daz, Persil and Surf.