Lecture 6

Question 1

Why is high pressure equipment used?

Answer 1

• for gas liquid reactions

Question 2

Why is pressurised equipment dangerous?

Answer 2

• Dangerous due to stored enegy and risk of explosion/ gas release if the equipment ruptures

• Many gasses used in synthesis are flammable, toxic and corrosive
• Each 1 mL gas stores 12 kJ energy

Question 3

How does flow chemistry minimise the dangers of pressurised reactions?

Answer 3

• Flow chemistry minimises the risk associated with this reaction by decreasing the volume of the system and therefore the amount of stored energy

Question 4

How do TBR/ PBR work?

Answer 4

• uses the downward movement of a liquid and gas over a packed bed of catalyst particles.
• It is used extensively used in processing plants.

Question 5

How does a bubble column work?

Answer 5

• A bubble column reactor consists of a cylindrical columns
• gas in-let is at the bottom of the column and causes a turbulent stream to enable an optimum gas exchange.
• The mixing is achieved by the gas sparging and it requires less energy than mechanical stirring.
• The liquid can be in parallel flow or counter-current.
• Better surface areas and mass transfer in solution

Question 6

Describe the different types of gas flow regime

Answer 6

• Can have flow where gas doesn’t touch the sides of a vessel
• Segmented Flow: As the size of the bubbles increase there is distinct separation of sections of liquid
• Annular flow: fast gas flow that breaks up segments with a thin coating of liquids on the inside of a channel. The contact surface area is extremely high

Question 7

How is flow regime determined?

Answer 7

by the physical properties of the liquid and the gas, with flow rate being very influential

Question 8

Describe a minature falling flow reactor

Answer 8

-liquid enters at one end and gas at the other. - Liquid flows down channels that have a gas layer above them leading to much more efficient mixing

Question 9

How do annular flow reactors work?

Answer 9

• up to 5m of reactor channel on an inch size reactor.
• A constant flow of gas forces liquid through the reactor with a very low residence time.
• Generating segmented flow means that the reaction coil can be shorter

Question 10

Why is fluorination hard in bulk conditions?

Answer 10

• Elemental fluorine is extremely reactive and oxidising and requires specialist equipment and training
• Selectivity can be difficult to predict and control
• Reactions requite care because hydrocarbons can uncontrollably burn in F2 analogous to combustion with oxygen

Question 11

Where do fluorination reactions occur?

Answer 11

• at the gas liquid phase interface

- due to the poor solubility of fluorine

Question 12

How do flow reactors improve fluorination?

Answer 12

• very high specific phase interfaces that serve to form the very thin liquid layer on the surface of the micro- structures, both heat transport and mass transport are intensified such that the formation of hot spots is suppressed and the selectivity of the reaction is improved.

• high conversion rates
• tailored selectivity (below 40% due to limiting chemistry)
• reaction time can be vaired
• improved space time yields

Question 13

How are flow reactors adapted for fluorination?

Answer 13

• Ni or polymer reaction channels instead of glass to prevent unwanted reactions
• Flourine can be diluted with nitrogen to lower reactivity

Question 14

What specific reactors are god for fluorination?

Answer 14

• Both falling film and microbubble reactors offer advantages for fluorination
• Selectivity better in a falling film reactor much higher than normal bubble reactors for toluene

Question 15

Why are hydrogenation reactions useful?

Answer 15

• catalytic hydrogenation reactions are commonly used for saturating double bonds and effecting functional group conversions
• Hydrogenation processes are of enormous industrial importance and are used on large scales in the petrochemical, fine chemical and food industries.

Question 16

What are traditional catalytic methods for hydrogenation?

Answer 16

• Heterogeneous catalytic hydrogenation methods were established in the early 1900’s followed by advances in homogenous catalysis using transition metal catalysts in 1960’s.
• The discovery of asymmetric transition metal hydrogenation reactions soon followed and paved the way for highly efficient syntheses of single enantiomers.
• Today, catalytic hydrogenation research continues at a pace with recent notable advances using cheaper transition metal catalysts, such as iron and cobalt, and also in the area metal free hydrogenations.

Question 17

What do modern catalytic hydrogenation reactions involve?

Answer 17

• Common with all hydrogenation methods involving molecular hydrogen is the need to ensure efficient mass transport of hydrogen gas into the liquid phase.

Question 18

Why are hydrogenation reactions dangerous?

Answer 18

• Owing to the poor solubility of molecular hydrogen in common organic solvents, hydrogenation processes are typically performed at elevated pressures and temperatures
• Such elevated temperatures and pressures have associated safety and cost implications and require speciality high pressure equipment.
• One of the key drivers for the development new catalysts is to achieve efficient conversions at lower pressures and temperatures

Question 19

Why is the use of molecular hydrogen green?

Answer 19

• good atom economy

- use of renewable feedstock

Question 20

How is wilkinsons catalyst used in micro reactors?

Answer 20

• Wilkinson was developed by adding a black coating to the inside of microchannels with a polymer of a Rhodium catalyst which was solid, turning the catalysis from homogeneous to heterogenous

Question 21

How can alkene/alkyne reactions and deptrotection reactions be done in flow?

Answer 21

• glass microchannel reactor with Pd0 immobilized on the inner surface of the channel.
• good yield
• production rate 140000 times higher than batch
• no Pd leaching therefore reusable reactors

Question 22

What are tube in tube reactions useful for?

Answer 22

• toxic gas reactions

- help hydrogenation reactions

Question 23

How can flow help the reduction of imines or nitriles to amines/imines?

Answer 23

• H-cube reactor
• supported precious metal catalyst (Pd/C, Pt/ C, or Rh/C). 30–80 bar of hydrogen pressure at 60– 80 oC
• stereoselectivity variations were observed depending on the metal catalyst and the temperature/pressure of the hydrogenation reaction.

Question 24

How is selectivity tuned in ethyl nicotine?

Answer 24

selectivity between partial and full hydrogenation could be tuned depending on the hydrogen pressure, solvent, and the choice of supported metal catalyst

Question 25

How can deuteration occur?

Answer 25

In the H-Cube hydrogen gas is generated by electrolysis of water changing the hydrogen source to deuterated water allows the preparation of deuterated derivatives.

Question 26

Why is palladium based carbonylation important?

Answer 26

• highly versatile
• effective synthetic route to an range of molecule
• one pot reactions
• readily available precursors

Question 27

Why can’t palladium based carbonylation be widely used?

Answer 27

• safety concerns with CO
• not as well categorised as other palladium based reactions
• yield depends substrate and CO pressure, solvent and reaction temperature
• emphasis place on development of catalyst that allows lower temps and pressures

Question 28

Describe carbonylation in flow

Answer 28

• low yield and selectivity but higher than batch reactions

- segmented flow set up

Question 29

How is carbonylation affected by flow regime?

Answer 29

see notes