Green Chemistry

Dr. Nguyễn Đăng Khoaa, Dr. Lê Vũ Hàa, Dr. Hồ Hoàng Phướcb

a Faculty of Chemical Engineering, Ho Chi Minh City University of Technology,
Vietnam
b Chemical Engineering, Competence Centre for Catalysis, Chalmers University of
Technology, Sweden
Contact: [email protected], [email protected], [email protected]
Off-line appointments (applied to the whole course): 9:00 – 10:00 Wednesday, 11:00 – 12:00 Thursday at 211B2
 Time Planned Content

Week 1 Introduction to Green Chemistry

Week 2
Week 3 The 12 principles of green chemistry
Week 4
Week 5
Week 6 Green improvements of chemical production: Catalysis
Week 7
Week 8
Week 9 Green improvements of chemical production: Solvents
Week 10
Week 11
Green improvments of chemical production: Renewable materials
Week 12

Week 13 Emerging Greener Technologies and Alternative Energy Sources

Week 14 Green improvement of industrial processes: Some examples
Week 15 Summarization
Texbook
1) P.C. Anastas and J.C. Warner ‘Green Chemistry Theory and Practice’, Oxford University Press, New York, 1998
2) M. Lancaster, GREEN CHEMISTRY: An Introductory Text, University of York, RSC, 2002

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 The 12 principles of Green Chemistry

Source: Center for Green Chemistry and Green Engineering at Yale

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 Outline
• Design for energy efficiency

• Technology for improved processes and energy efficiency

• Microreactor

• Photochemical reactions

• Chemistry using microwaves

• Sonochemistry

• Electrochemical synthesis

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 DESIGN FOR ENERGY EFFICIENCY
Representative scheme of a chemical plant

Energy Energy

Input Materials Product Product

Reactor
Purification
(feedstocks) T, P Byproduct
Waste
Catalyst Solvent

Preceding chapters This chapter

▪ Reduce waste
Improved process
▪ Lower harmful emissions Energy efficiency
▪ Improve process efficiency
▪ Renewable feedstocks
A way to reduce cost
▪ Sustainable/degradable products

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 DESIGN FOR ENERGY EFFICIENCY

Haber-Bosch Process
Energy
consumption
is now less
than 40%
than original
process

Some simple measures can be used to reduce cost:

Most chemical processes:
✓ Monitoring, control and maintenance
✓ Use thermal sources of energy from fossil fuels
✓ Loss prevention
✓ Most of energy is wasted in heat up reactors,
✓ Waste heat recovery
solvents, etc
✓ Matching energy sources to requirement

➢ Chemicals and petroleum refining industries → major energy users → 50% of industrial energy usage
➢ ¼ of energy → consumed in distillation and drying processes
➢ Necessity of considering the whole process, not just reaction stage when undertaking research and
development work

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 DESIGN FOR ENERGY EFFICIENCY

There are two competing processes of making TiO2

white pigment:

1. From chlorine and TiO2 rutile ore

2. From Ilmenite ore and sulfuric acid

➢ Process (2) consumes a lot of energy for evaporation (calcination step)

➢ Energy consumption: process (2) = 5 x process (1)

➢ Both processes are still in use, although cloride process is dominate. Why?

➢ Process (2) can use lower grade ores (less expensive ores)

➢ Process (2) → produce both anatase + rutile while process (1) → only rutile

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 REACTORS FOR PHARMACEUTICAL SYNTHESIS?
Two common synthesis processes in industry https://labchem-wako.fujifilm.com/us/category/synthesis/flow_synthesis/index.html

Fine chemicals, e.g. pharma Petroleum, bulk chemicals

https://www.brinox.eu/pharma/units-production-active-pharmaceutical-ingredients https://www.eia.gov/todayinenergy/detail.php?id=9650
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 Types of reactor for fine chemical industry

Chemical reactors

Continuous stirring Plug Flow Reactor Semi-batch reactor

Batch reactor
tank (CSTR) (FPR)

https://www.promix-
https://www.climate-policy-watcher.org/food- solutions.com/en/cooling/cooling-polymer-
(Copyright DCI Inc., St. Cloud, MN) processing/continuously-stirred-tank-reactor-
production
cstr.html
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 Video 13.1 Introduction to Flow Manufacturing

https://www.youtube.com/watch?v=WlvAwCFKIZA

Question Short Answer

1) What is the main problem of batch synthesis?

2) What are the advantages when using flow synthesis

compared to batch synthesis?

3) Give some advantages of flow vs batch in the production of

carbapenem?

4) Give 3 examples of reactions in pharmaceutical synthesis

that can apply the Continuous Flow Technology?

https://www.brinox.eu/pharma/units-production-active-pharmaceutical-ingredients https://www.eia.gov/todayinenergy/detail.php?id=9650
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 REACTORS FOR PHARMACEUTICAL SYNTHESIS?
Pharma industry still relies on multipurpose batch or semibatch reactors, it is evident that
interest is arising toward continuous flow manufacturing of organic molecules, including highly
functionalized and chiral compounds.
Org. Process Res. Dev. 2016, 20, 1, 2–25

Lab scale Pilot scale Commercial scale

Issues of scaling up a pharmaceutical synthesis process
- Cost of starting materials
- Toxic chemicals, safety
- Mass and heat transfer control
- Selectivity and yield by synthesis condition
- Space to set up
- Cost of purification
Continuous flow reactor
+ Microreactor/
microscale microfluidic channels/
microstructured reactor/
http://www.essentialchemicalindustry.org/ microchannel reactor
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 Role of diffusion
Da < 1 → reaction rate < diffusion rate
Damköhler number (Da)
Da > 1 → reaction rate > diffusion rate

✓ Mixing
✓ Interfacial Surface Area

Chem. Rev. 2017, 117, 18, 11796–11893

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 Microreactor

A microreactor is a continuous flow-type

reactor in which a chemical reaction take
place in microchannels with dimensions
below 1 mm.
Depending on the size of channel:
Microfluidics: 10-500 µm
Millifluidics: 500 µm to several mm
https://doi.org/10.1038/srep05443

Micro-sized channels
Biomicrofluidics. 2014 Sep; 8(5): 054101.
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 Flow chemistry

Chem. Rev. 2017, 117, 18, 11796–11893

Flow chemistry involves the use of channels or tubing to conduct a reaction in a

continuous stream rather than in a flask

supported reagents
or catalysts

microwave irradiation
Combination photochemistry
Flow chemistry new solvent systems

inductive heating

electrochemistry

3D printing Org. Process Res. Dev. 2016, 20, 1, 2–25

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 Flow chemistry

Chem. Rev. 2017, 117, 18, 11796–11893

Types of continuous flow systems

Example. Continuous Flow Synthesis of

Diphenhydramine Hydrochloride

chlorodiphenylmethane

Tube 0.5 mm
Yield > 90%

dimethylethanolamine

Org. Process Res. Dev. 2016, 20, 1, 2–25

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 Applications of micro processing technology
Video 13.2 Micro processing techniques save material and energy in the chemical industry
https://www.youtube.com/watch?v=xUgckfuSYh0

Question Short Answer

1) What are the problems of batch reactor (vessel) in
pharmaceutical synthesis?

2) What does mmRS stand for?

3) What are the advantages when using microreactor for

lithium reaction?

4) What is the surface to volume ratio of the MIT prove

microreactor?

5) What are the advantages of microreactor system?

6) What is the position of Germany in the world’s chemical

supplier (in the video, 2017)?
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 Advantages of microreactor systems

• Large surface-to-volume ratio

• Precise control of reaction temperature

• Extreme exothermic reaction can be adequately cooled

• Safety for reactions with highly explosive reagents

• Easily controllable and safe process

• Few by products

• Well-defined process → upscaling relatively simple

• Small space for setup

• Reduction of hazardous waste

• Cost-effective, time-saving, flexible

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 Advantages of microreactor systems

• Scale-out: process is optimized & reactor is designed only once in Lab

• Increasing production volume can be easily obtained by assembly more
number of reactors

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 Flow chemistry

Continuous Flow Synthesis of Rufinamide

Conventional method:
Reaction between 41 and 43

Problem:
▪ Azide compound is not
stable
▪ Possible formation of HN3
(hydrazoic acid) → highly
toxic and explosive

Flow chemistry:
Minimize the hazardous
handling of organic
Org. Process Res. Dev. 2016, 20, 1, 2–25
azides

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 Example of Flow chemistry

97% yield

84% yield
✓ Tamoxifen: treatment for breast cancer
✓ Combine 4 different chemicals transformation into one stream
✓ Reducing risks for handle of organometallic reagents
✓ 80 min → 12.4g of pure API → one patient’s treatment for over 900 days
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 Example of Flow chemistry

84% yield

✓ 3 min for production of Ibuprofen

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 Microwave-assisted synthesis

▪ Microwave → wavelength between 1 mm and 1 m → similar to radar and telecommunication devices

▪ Most microwave operates at fixed wavelength at 2.45 GHz
▪ Microwaves only heat a certain substances and not others, is termed dipolarization
▪ Reagents with dipole moment (e.g. H2O) will align itself to electromagnetic field by rotation
▪ This rotation of molecule creates friction → heat
▪ Note that microwave will not influence (no heat) non-polar solvents

Video 13.3 How does a Microwave Oven Works

https://www.youtube.com/watch?v=KLzUoW0InnQ
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 Microwave-assisted synthesis

Video 13.4 Microwaveable solvents - solvent polarity demonstration

https://www.youtube.com/watch?v=Ip6ZA8UYvgM

Watch the video and answer two questions:

1) What in the balloon made the flow of water changed direction?
2) What is the conclusion from the example of heating water and gasoline by
microwave oven?

Question: Which solvent can be quickly heated in a microwave-assisted synthesis?

a) Hexane b) CCl4 c) Benzene d) DMF

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 Examples of Microwave-assisted synthesis

Yield > 85%

Solvent-free process

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 Sonochemistry

▪ Ultrasound refers to sound waves > those detectable by the human ear (i.e. around 18 kHz)
▪ The ultrasound frequencies of interest for chemical reactions (typically 20–100 kHz) are much lower than
used for medical applications
▪ Applying ultrasound in a liquid media → molecules oscillate around their mean position → bubble
formation → collapse of bubbles → very high local temperature (5000 oC) and pressure (e.g. >500 bar) →
initiate the chemical reaction
Video 13.5 https://www.youtube.com/watch?v=okYqH3AxQAw

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 Examples of Sonochemistry and Green Chemistry

Switching pathways with ultrasound

Sonication in water at temperatures in the range

22–45 oC gave virtually quantitative yields.
Whilst the high yields have been attributed more
to the solvent than to the sonication it is a good
example of what can be achieved by combining
green technologies.
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 Photochemistry
The use of light, at various wavelengths, as a source of energy to activate/charge
catalysts to perform chemical transformations

https://factmyth.com/factoids/visible-light-is-electromagnetic-radiation/
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 Photochemistry
▪ Atom or molecule involved must absorb light (Grotthuss-Draper law)
▪ One photon of light can only active one molecule (Stark-Einstein law)

Here are the types of photochemical reactions:

•Photo-dissociation: AB + hν → A* + B*
•Photo-induced rearrangements, isomerization: A + hν → B
•Photo-addition: A + B + hν → AB
•Photo-substitution: A + BC + hν → AB + C
•Photo-redox reactions: A + B + hν → A– + B+
https://www.chemistrylearner.com/chemical-reactions/photochemical-reaction
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 Photochemistry

3 O2 + hν → 2 O3

https://upload.wikimedia.org/wikipedia/commons/2/27/Photosynthesis_Images.jpg

https://www.chemistrylearner.com/chemical-reactions/photochemical-reaction
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 Photochemistry

Advantages Disadvantages

• Photon → clean reagent → • Reactor fouling is a fairly common problem

no residues.
• Radiation of a particular wavelength
• The energy is more directed (monochromatic) is required to initiate a specific
→ low temperature → high electronic transition, but most UV and visible
selectivity, less byproduct light sources are polychromatic
formation
• Light sources are often expensive, especially if
• Some reaction pathways are made of thick-walled quartz as in high-pressure
more readily available via mercury lamps → cost
photochemical processes →
can produce some products • Since the power of transmitted light drops off as
the square of the distance from the light, for
that would be difficult to make
efficient reaction and energy usage the
by other routes reactants must be as close as possible to the
light source. This has practical implications for
the design of industrial reactors.

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 Famous examples of Photochemistry in industry

The caprolactam process, 100 000 Vitamin D3 synthesis

ton per year by Toray

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 Microreactor and photochemistry

Example
the oxidation of α-terpinene

Different arrangements for photochemistry

in a coil reactor unit

Chem. Rev. 2017, 117, 18, 11796–11893

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 Electrochemical synthesis

▪ Effluent treatment ▪ Oten water-based process

▪ Corrosion prevention ▪ Usually mild operating conditions (relatively energy efficient)
▪ Electroplating ▪ Atom efficient – replacement of reagents by electrons
▪ Electrochemical synthesis ▪ Novel chemistry possible

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 Electrochemical synthesis

▪ Effluent treatment ▪ Oten water-based process

▪ Corrosion prevention ▪ Usually mild operating conditions (relatively energy efficient)
▪ Electroplating ▪ Atom efficient – replacement of reagents by electrons
▪ Electrochemical synthesis ▪ Novel chemistry possible

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 Summary

• Energy consumption, particularly for large-volume chemicals → taken

seriously by industry for many years.

• Combinations of new processes such as catalytic ones, improved

engineering designs (flow chemistry, microreactor), and “good
housekeeping” → reduce energy use.

• The average research chemist still do not consider particularly important

energy consumption.

• Emergency of technologies = alternative forms of input energy (i.e.

microwave and ultrasound) + renewed interest in photo chemistry and
electrochemistry → green chemistry → more energy efficient and cleaner
• 3D printing plays an important role in microreactor design

Source: Center for Green Chemistry and Green Engineering at Yale

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