Introduction to PAT & Inorganic Mechanisms Flashcards
What is Process Analytical Technology (PAT)?
- Its about understanding, monitoring and controlling processes
- Its a system for designing, analysising, controling in-line manufacturing process through timely measurements with good quality and performance, which the goal is to ensure final product quality and performance
PAT can be…
The use of rapid off-line, at-line, on-line or in-line analysers to obtain analytical data
What is the core benefit of PAT?
The sucess of PAT is related to the knowledge gained about the process and not the volume of data generated
What is the difference between the application of the UN STG and the triple bottom like in chemistry?
- The UN STGs puts into “context” why studying chemistry may have relevance
- The Triple Bottom Line method asks you to see profit that your business makes socially, environmentally, and economically
What is the main idea around the 12 Principles of Green Chemistry
They are a checklist for judging how green your process is
A process doesn’t necessarily need to satify every Principle…
… BUT the more principles that are satified, the greener the process is
What are some potential issues with the 12 Principles of Green Chemistry?
- Green Chemistry aims to satisfy the 12 Principles which address most of the enviornmental issues
- BUT it does not necessarily address societal or econmic issues
- This is important because societal, economic and environmental issues are all crucial to sustainability - triple bottom line
The first principle of green chemistry is: Prevent Waste
How does this relate to PAT?
- The use of Green chemistry principles and PAT monitoring can reduce the number of out of specification batches and impurities
- When companies apply green chemistry principles to the design of the API process, dramatic reductions in waste are often achieved, sometimes as much as ten-fold
- So, it is important to entent to all parts of the drug industry, especially the biopharma and generic sectors, as well as to other sectors of the chemical enterprise where synthetic chemistry is used to produce their products
The second principle of green chemistry is: Atom Economy
How does this relate to PAT?
- During reaction chemistry you can monitor the consumption of the reactants and products to:
- Prevent un-reacted mateiral as impurities
- Maximise yield get the most out of each reactant
- End the reaction when the reactants are used up and the product is at a maximum yield to prevent degradation and unwanted materials and lowering yield
The sixth principle of green chemistry is: Design for Energy Efficiency
How does this relate to PAT?
- Using process monitoring you can determine when a process is done and turn off heating, agitation, and other processes
- Examples include: Reaction chemistry, crystallisation and form conversion, drying and blending
The 8th, 9th and 10th principle of green chemistry is: Reduce derivatives, Catalysis & Design for Degradation
How does this relate to PAT?
- Real-Time analysis for pollution prevention
- Using process monitoring you can:
- Reduce derivated and monitor catalysis to optimise reaction chemistry and minimse derivative
- Ensure crystallisation and correct polymorph (crystalline form)
- Avoid over-drying and degradation
- You cannot control pollutants that you cannot detect
How does this diagram relate to reaction chemistry?
There are multiple ways to proceed with a reaction
Reaction mechanisms are of central importance for catalysis equilibria, kinetics, mechanisms and ligand substitution
When considering these reactions, we are concerned with…
- The reactants; the ground state of the reaction
- The transition states of the reaction
- The identification of intermediates
- Employing kinetic methods to determine the rate law
- Elucidating the reaction stoichiometry
Metal carbonyls bond through sigma donation and pi backbonding
How can we spectroscopically analyse this?
- The position of the IR band
- The back-donation puts electron density into the antibonding orbital which weakens this M-C bond
- The position of the band shift up when there is a weaker M-C bond
The following reaction is catalysis of hydroformylation
How many different structures of the intermediate can exist?
8 different structures
What is the difference between a transition state and a intermediate?
Draw their reaction coordinate
(you can measure the intermediate, you cannot measure the transition state)
For an SN1 reaction with the following rate determining step, what is the rate equation?
(1st order)
For an SN2 reaction with the following rate determining step, what is the rate equation?
(2nd order)
What is the classification for Y and X within this inorganic reaction
Y = Entering group
X = Leaving group
Consider the following reaction: ML₅X + Y → ML₅Y + X
If the rate determing step is
- This is a dissociative (D) mechanism
- The intermediate has a reduce coordination number
- And the rate is largely indepedent of incoming ligands
Consider the following reaction: ML₅X + Y → ML₅Y + X
If the rate determining step is
- Associative (A) mechanism
- The intermediate has an increased coordiation number
- The rate strongly depends on Y
Consider the following reaction: ML₅X + Y → ML₅Y + X
If the rate determining step is
- Interchange mechanism
- Reactant form a loose complex - outer sphere
- No detectable intermediate - transition state
- Interchange between ligands in the inner and next coordination sphere
What are the requirements for an interchange mechanism to occur?
- As the M-X bond starts to break, M begins to form a new bond with Y
- The entering group Y must be present in the region around the complex ML₅X when the M-X bond begins to break
- Thus before the substitution occurs, Y must enter the ‘outer sphere’ of L₅MX
What is the difference for Id and Ia for interchange mechanisms?
- Id - rate determining step in the outer sphere → bond breaking more important than bond making
- Ia - rate determining step in outer sphere → bond making more important than bond breaking
If you were to consider if a mechanisms is a D or A type, you could consider kinetic, how?
For ML₅X + Y → ML₅Y + X
(looking at rate law)
What is the issue with using kinetic to consider if a mechanism if D or A?
- Need to be careful when interpreting kinetics
- Difficult to get mechanism soley from rate law
- Simpler rate law → less certain - mechanism
- What about interchange?
The following equation is the Arrenhius, if you plot Ln(k) against 1/T, what is the slope and intersect equal to?
Slope = -Ea/R
Incercept = Ln(A)
A = activation energy
What is the difference between the Eyring Plot vs Arrenhius Plot?
What is the slope and intercept equal to in the case of Eyring?
- Plot Ln(k/T) vs 1/T
- Slope = -ΔH‡/R
- Intercept = 23.8 + ΔS‡/R
How can the values of ΔS help work out if a reaction mechanism is D, A, Id, or Ia?
Consider the following scenario, what type of mechanism is it?
- Large negative ΔS
- Meaning A mechanism
Between A and D mechanisms, there are two interchangable mechanisms being…
Ia and Id
What is the problems around using ΔS to work out the type of mechanism?
- ΔS is worked out from the intercept, therefore affected by error in the gradient
- Need to be carefull when looking at numbers slightly above or below zero
- Ultimately, you need very good data to do this
What is the volume of activation (ΔV‡)?
- The volume of activation is the partial molar volume change when reactant are converted to products
- Obtained from the plot of ln(k) vs P
- (uses high pressures up to 200 MPa - sight disadvantage)
How can we use ΔV‡ to work out if bonds are being broken or made within a reaction
What is the issues with working out ΔV‡
- These measurements are difficult as they require very high pressure and specalisatic equipment
