Dr. Joshua Barham

Learning Objectives

By the end of this course, you should
possess the following competencies:

·        
Knowledge about
important industries, industrial compound classes and scales

·        
Knowledge about
particular organic reactions used in industry

·        
Knowledge about
important industrial processes

·        
Basic knowledge
on biosynthetic pathways and some basic medicinal chemistry concepts

--> You should be able to attend a medicinal chemistry lecture
and understand what metrics are used to assess the efficacy and selectivity of
a bioactive compound

·        
Basic knowledge
on process chemistry and green chemistry

--> You should have an appreciation of the factors driving
‘route selection’ in industry, the kinds of techniques used/avoided and how
reactions are optimized

·        
Appreciation of
advanced manufacturing technologies

--> You will appreciate how advanced chemical and manufacturing
technologies are changing the ways chemists do industrial synthesis

By the end of this course, the
following operational skills will be expected of you:

·        
Graphical
reproduction of key compounds, intermediates and catalytic cycles

·        
Verbally and
graphically rationalizing fundamental aspects of industrial (and bio) synthetic
reaction schemes

·        
Independent
recognition of analogies and differences between industrial and lab-scale
synthesis

·        
Independent
recognition of analogies and differences between different types of chemical
industries

A unique aspect of this course is the opportunity to interact with/gain insight from real-world Industrial Chemists, with >10 years of experience in the pharmaceutical/agrochemical/organic functional material industries. External speaker lectures will be arranged on ZOOM or, if possible, in presence

***Lecture
content and schedule will change and is subject to availability and number of external
speakers***

Lecture 1         Introduction, Types of Industry, Sustainable Chemistry

Lecture 2         Dyes, Pigments, Fragrances, Flavors

Lecture 3         Commodity Chemicals, Fuel & Energy

Tutorial I        (Tutorial on lecture material)

Lecture 4         Functional Materials

Lecture 5         Asymmetric Synthesis, Redox Reactions

Lecture 6         Crop Protection

Lecture 7         Pharmaceuticals I - Drug Discovery, Alkaloids, Opiates

Lecture 8         Pharmaceuticals II - ACE Inhibitors, Prostaglandins

Lecture 9         External Speaker
1:
TBA

Dates/Times:

This lecture will be given as a block course by a visiting Professor, Prof. Hyunwoo Kim from South Korea (Pohang University of Science and Technology "POSTECH"), who will be visiting our university in January/February 2023. https://lexontkfu.wixsite.com/hyunwookimlab

The lecture will take place on: Tuesdays 08-10 (CH12.0.18) January 10th, 17th, 24th and 31st. 

Students are expected also to attend Prof. Reiser's lecture slot (Vorlesung 'Moderne Synthesemethoden') Monday 10-12 a.m. (H47), January 16th, 23rd,

and Prof. Reiser's seminar slot (Seminar zur Vorlesung 'Moderne Synthesemethoden') on: Friday10-12 (H52), January 20th.

Credits: 
The course is worth 3.0 credits (2 SWS). In order to complete the course, students must attend lectures and complete a coursework assignment.

Content: (Draft - subject to change)

Jan 10 (Tue 8-10, CH12.0.18): 
- Importance of electroorganic synthesis in organic chemistry & industry.
- Cathodic reductions: Birch-type reduction, olefin functionalization, reductive cross-couplings (cross-electrophile coupling)
Jan 16 (Mon 10-12, H47):
- Basic introduction to electroorganic synthesis. Cyclic voltammetry, organic E-chem cell configuration. Calculating reaction efficiency
- Anodic oxidations 1: Kolbe reaction, Shono-type oxidation, cation-pool strategy, alcohol oxidation, 
Jan 17 (Tue 8-10, CH12.0.18):
- Paired electrolysis: Parallel paired electrolysis, divergent paired electrolysis
Jan 20 (Fri 10-12, H52): Seminar with workshop to consolidate knowledge from Jan 16 lecture.

- Workshop on Anodic oxidation chemistry

Jan 23 (Mon 10-12, H47):

- Anodic oxidations 2: N-centered radicals, Arene oxidation, alkene oxidation, C-H bond oxidation 

Jan 24 (Tue 8-10, CH12.0.18):

- Electrogenerated reagents; case studies

- Asymmetric organic electrosynthesis

Jan 31 (Tue 8-10, CH12.0.18): 

- Electrophotocatalysis; merging electricity and light to achieve elusive transformations

Context and Importance of the Course:

Electroorganic synthesis has historically found applications in the synthesis of bulk chemicals. i) The Baizer process for the industrial synthesis of adiponitrile and ii) the synthesis of dimethoxycyclopentene - are realized by electrochemistry on megaton scaled per year to date for several decades. No chemical process comes close to the efficiency, economy, and sustainability of electrosynthesis in these cases.

Electroorganic synthesis is now receiving dramatic attention in the fine and pharmaceutical chemical industries, thanks to the standardization of small-scale batch lab equipment and increasing educational uptake. A review: https://pubs.acs.org/doi/10.1021/acs.chemrev.7b00397
Since electrons/holes are cheaper than chemical oxidants/reductants and cheaper than artificial photons of light, education and investment in electrochemistry is critical as Europe moves toward a more energy-sustainable future of chemical synthesis.

In Germany, this is recognized by three recent national funding initiatives:

i) Fonds der Chemischen Industrie ‘Etablierung neuer Lehrmethoden im Chemiestudium: Thema II: Elektrochemie'

ii) (U.S.A.)National Science Foundation+German Science Foundation (DFG) Lead Agency Activity in Electrosynthesis and Electrocatalysis

iii) German Science Foundation Special Priority Programme (SPP) 2370 “Nitroconversion”

This course is designed for those interested to learn about the key role of organic synthesis in the "real world" of industry. It will examine:

1) Why the following entities are important, how were they discovered are how are they synthesized?

Pharmaceuticals (alkaloids, statins, prostaglandins, NSAIDS)
Dyes (indigo, alizarin)
Fragrances & Fragrances (terpenes)
Agrochemicals 
Functional materials (organic photovoltaics, liquid crystals)
Bulk chemicals

2) What are the most widely-used chemical transformations?
(e.g. CO- and CO2-harnessing reactions, asymmetric catalysis) 

3) How are synthetic methods changing in industry?
(biocatalysis, photocatalysis)

4) How are chemical reactions done on the kilo- or tonne- scale?
(batch vs flow chemistry, thermal runaway, kilo/tonne-lab equipment)

5) What is 'Green Chemistry', why is it important and how does one quantify a sustainable process?

6) What is the 'Drug Discovery Process'; how to bring a drug from 'hit to market'

7) How does industry choose a chemical synthetic route?

The course features interactive exercises to consolidate learnings from each lecture.

Learning objectives

This course will provide you with: 

• Knowledge about important industrial compound classes (dyes, fragrances / flavors, pharmaceuticals, crop protectants)
• Knowledge about particular organic reactions
• Knowledge about the types of chemistry and reactor platforms used in industrial synthetic processes
• Basic knowledge on the principles of medicinal chemistry, flow chemistry and green chemistry
• An appreciation for how bioactive molecules are made in nature vs. industry 
• An organized lecture on the drug discovery process and synthesis in medicinal chemistry from an expert in the pharmaceutical industry (Dr. Rob Young, GlaxoSmithKline)
• An organized lecture on process development from an expert in the agrochemical industry (Dr. ???, Bayer)
• Case studies on the industrial synthesis of analgesics, antimalarials and anti-cancer drugs.

By the end of this course, you should be able to:

• Reproduce the structures of key compounds and intermediates
• Rationalize the fundamental aspects of industrial synthetic reaction schemes
• Appreciate similarities and differences between lab-scale and industrial synthesis
• Compare and contrast the different reactor platforms industry uses to scale chemical processes (batch, continuous flow)
• Explain the principles of green chemistry and be familiar with the industrial metrics used in this respect
• Appreciate the nature, time and cost of the drug discovery process from hit to drug; from discovery to production
• Understand the fundamental principles of medicinal chemistry related to the characterization of a drug
• Appreciate the differences in purpose, scale and requirements of pharmaceutical, agrochemical, fine chemical and petrochemical synthesis

This course will NOT cover:

• Petrochemicals
• Polymerizations
• Fine and Commodity Chemical Synthesis