Synthetic Electrochemistry

how to predict if a reaction will proceed

by calculating the electricical potential of the electrochemcial cell:

• reduction potential = tendency to take up electrons referenced to the standard hydrogen electrode

  • more positive is more oxidative power and will be reduced itself

• standard reduction potential = reduction potential under standard conditions

• Nernst equation

• use standard reduction potentials, concentration of the reacting species and temperature to calculate the electrical potential under non-standard conditions

• The reaction proceeds if

  • ΔE = E (reduction) - E(oxidation) >0

  • the reaction proceeds with strong oxidzing agents (induce reduction, high reduction potential) with strong reducing agent (induce oxidation, low reduction potential)

Caveats

• data have to be compared under the same conditons (ref electrode, solvent,…)

• it is thermodynamic data, says nothing about kinetcis

  • a positive cell potential means a negative delta G, meaning spontaneous reaction

  • but reaction can be thermodynamically favorable but still slow if activation barrier to high

• E^∘ tells you the inherent tendency of the reaction and the position of equilibrium.

• E tells you whether the reaction is spontaneous under the actual conditions present.

movement of electrons

Electrochemical cell

• oxidation and reduction occur in separate cell compartments

• electrons from oxidaiton half cell to reduction half cell trhough an external conductor

• this leads to charge build up, stopping electron flow, rapidly reacing equilibrium

Solution

• maintaing charge ballance through ions

  • salt bride or ion-exchange membrane

• for every mole of electrons transfered at an electrode, an equivalent amount of ionic charge must move

Equilibrium:

• at specific concentrations, the cell has a certain voltage

• as the reaction proceeds, conc change

• therefore E gradually decreases (Q becomes K)

• when E = 0, reaction reached chemical equilibrium

Types of electrochemical cell

• Galvanic/Voltaic cell

  • electrochemical cell that converts chemical energy into electrical energy

• Electrolytical cell

  • electrochemical cell that converts electrical energy into chemcial energy

Rechargeable battery can work in both directions

• During discharge: bhaves like galvanic cell

• during charge: electrolytical cell

Physical quantities

• Electric current

  • flow of electric charge in a cricuit per unit time

• current density

  • amount of current flowing through a unit area

• electric potential

  • amount of work need to move a charge from one point to another inside an electric field

  • voltage is the potential difference

Key laws

Ohm’s lawy: V = I x R

Watt’s law: P = V x I

voltage is like water pressure: the higher the pressure the higher the flow

• potential difference between electrodes pushes electrons through the circuit like pressure pushes water through a hose

current is like the flow of water: how much charge flows per second and is influence by the size of the hose

resistance is like sand in the hose blokcing flow

electrochemical cell in action

1. voltage is applied

2. ions move in electrolyte while electrons move through external circuit

   1. no redox happens yet

3. only when voltage becomes high enough, it reaches a potential where molecules can give away electrons at the anode (oxidation) and accept electrons at the cathode (reduction)

   1. electrons move from the anode to the cathode

• But you often need to apply a higher voltage than the theoretical value calculated through the Nernst equation before the reaction actually starts

  • extra required voltage = overpotential

  • = differnce of theoretical and experimentally determined electrochemical potential difference

iRcell = loss in potential due to solution resistance

(depends on distance electrodes and conductivity of electrolyte)

Electrochemical window

Electrochemical window (EW) of a substance is the voltage range between which a substance is neither oxidized nor reduced

every component in the reaction mixture has an anodic and cathodic limit

Electrochemical reaction can only occur if the applied voltage is larger than the cell voltage, this causes:

• charge imbalance: compensated by transport of ions

• Consumption of substrate: substrates need to keep moving to the electrode

Therefore mass transfer is important (3 modes)

• diffusion = transfer from region of high conc to lower conc

  • slow

• migration = transfer of charge under influence of an electric field

  • fast

• convection = transfer due to bulk motion of a fluid

Layers at the electrode

• double layer: 1-10 nm

• diffusion layer: 1-100 µm

  • depends on convection (confusing name)

—> situation at the electrode is totally different form the bulk (conc, solvation, pH)

Change in concentration over time

1. V = 0: reactant concentration is the same everywhere in the cell

2. when V_applied > V_cell

   1. reactants are consumed and product is formed

3. conc at electrode become different from the bulk creating a concentration gradient

   1. reactants have to move from the bulk to the electrode (mainly via diffusion)

4. Transient phase

   1. concentration profile is till changing over time

5. steady state

   1. reactant is consumed at the electrode but new reactant arrives at the same rate from the bulk

6. the total reactant concentration decreases while product concentration increase until all reactant is consumed

—> current is dependent on electron transfer rate of the substrates and mass transport to the electrodes

Limiting current

• as the potential incrases the electrode becomes a stronger oxidizing or reducing surface so electron transfer bcomes faster so current increases

• at higher potential the electron transfer becomes so fast that every molecule arriving at the electrode reacts immediately

  • this is the electron transfer limit

  • current is now only determined by the rate of mass transfer

• Then the limitting current is reached

  • increased voltage does not lead to increase in current because the reactants cannot reach the electrode fast enough

depends on number of electrons, electrode surface area, concentration and mass transport coefficient

Operation modes

Galvanostic = constant current

• current is kept constant, while the system adjusts the potential to keep it constant

• at beginning: linear conversion because substrate conc is high

• but due to decreasing concentration, at certain point mass transfer becomes limiting factor

• potential needs to increase to maintain the same current level

• if potential becomes too high it can cause side reaction

• so good if you want a predicatble conversion rate but can be less eselective

Potentiostatic = constant potential

• Potential is kept constant

• at beginning current is high because substrate concentration is high

• over time concentration drops and therefore current drops as well meaning the reaction slows down over time

• good for selectivity as potential doesn’t become too high but less productive as current drops

Electrode

= source of infinite oxidizing or reducing power generating no waste (if inert, sacrificial electrodes are consumed)

classifications:

• working electrode

  • where target reaction occurs

• counter electrode

  • used to complete the external circuit

• reference electrode

  • has a stable known potential

  • does not participate in the reaction

  • used as a fixed reference to accurately control the potential at the working electrode (potentiostaci experiments

Electode materials

• carbon based electrodes (stable, conductive, often cheaper than noble metals)

  • graphite

    • cheap but oxidized at high potential (to eg CO2) so it slowly degrades

  • boron doped diamond (new and wide electrochemical window)

• Platinum

  • common

  • stable + conductive

  • but expensive (not scalable)

• oxides

  • ITO (transparant)

• gas diffusion electrod

  • used when reactant is a gas

  • A gas diffusion electrode brings a gas directly to a catalyst through porous layers, while the liquid electrolyte reaches the catalyst from the other side.

  • at catalytic layer: gas electrons and electrolyte meat and redox reaction occurs

  • electrons are provided or conducted by the current colector that travel through conductive parts of the micro and macroporous layers

  • The main challenge is flooding:

    • if too much liquid enters the pores, gas transport is blocked

    • then the electrode becomes less efficient

• photoelectrode

  • absorb light adn create excited charges (electrons and holes)

  • these charges can drive electrochemical reactions at the elctrode surface

  • eg. electrons can cause reduction and holes oxidation

Electrolyte solution components

Substrate

Solvent

• Considerations

  • Electric conductivity

    • low for organic solvetns but high for ionic liquids

  • participation in reaction

    • counter reaction

      • must balance the reaction at the working electrode by a counter reaction at the counter electrode

      • protic solvents could serve as a proton source for oxidation reactions with H+—> H2 reduciton as counter

    • electrochemcical winow

    • stabilization of intermeidates

      • fluorinated alcohols can stabilize radicals well

• Protic

  • MeOH, water, acetic acids, fluorinated alcohols

• Aprotic

  • ACN, THF, DCM

• ionic liquids

Electrolytes

Added to lower resistance and increase conductivity, lower resistance is obtained form ions with highest mobility: smaller size and decreased coordinating properties

• Considerations

  • must be chose carefully because they affect cost, purification, stability, recycling potential, solubility and selectivity

• Cations

  • tetraalkyl ammonium salts

    • balance chain length for solubility and size for mobility

    • TBA used a lot

  • Alkali metal salts: Na⁺ or Li⁺

• Anions

  • halides: Cl-, Br-

    • risk at oxidation at high potential

  • PF₆^- ot BF₄^-: non coordinating

  • ClO₄^- can act as weak oxidant but explosive in post processing

Additives

increase reaction performance

Interfering compounds

• oxygen

  • can get reduced to superoxide leading to side reactions

  • degass

• Water

  • can lead to water oxidation or reduction = electrolysis

  • drying recommended

Electrochemical cell designs

Undivided vs divide cell or Batch vs flow cell

Undivided:

• allows interference of reaction components

• simple set-up + cost-effective —> preferred in industry

• Disadvantages

  • Chemical shortcut: products oxidized at anode can get reduced again at the cathode if electrodes too close = energy waste

  • Not the case for electroplating

    • here the metal ion is reduced and deposited on the electrode

Divided

• retains conductivity while retaining conductivity

  • separator allows allows ion transport but inhibits transport of reagents

  • Avoids interference reation components

undivided cell is industrially preferred although this is not allways beneficial or possible

Batch vs Flow electrochemistry

Batch= reaction mixture is placed in one vessel and stirred

• Traditional setup and common in industry

Flow = reaction mixture flows between 2 electrodes

• operation mode

  • single pass = continuous

    • if counter reaction gas formation, bubbles form that can reduce accessability to the electrodes —> need recirculation

  • recirculation = outcome is reinjected

• scale up

  • batch: difficult because larger vessels give poorer mixing and less uniform current distribution

  • Flow: easier by running longer, increasing flow

interelectrode gap

as small as possible

zero gap cell

electrodes are placed very coste togheter only sepearated by a membrane

• the small gap lowers the electrolyte resistance of the cell

• this means less voltage is lost and the process is more energy efficient

• the electrodes are porus, so electrolytes and gasses can move through them

often used for water electrolysis (production of O2, H2)

Operational modes of the power supply

Galvanostic (constant current)

most used in industrial settings

• 2 electrode system (less expensive)

• more control (exact equivalents of electrons knwon)

• better space time yield

• but voltage increase can lead to undesired side reactions

Potentiostatic (constant voltage)

• more selective: less side reactions

• need reference electrode (more expensive)

• full conversion often not achieved

Voltage regime

• DC (direct current)

  • curren flows in one direction only

  • like battery

• AC (alternating current)

  • current changes direction back and forth

—> DC usually for electrochemsitry because you want oxidation at one electrode and reduction at the other. with AC the roles would switch continuously

Continuous vs pulsed voltage regime

• continuous

  • current is applied at all time and the reaction proceeds continuously

  • simple and productive

  • but can cause side reactions

• Pulsed current

  • Current switches on and off (DC) or changes polarity in a pulsed way (AC)

  • during ‘on’ electrochemcial reacition occurs

  • during ‘off’ new substrates can diffuse to the electrode

  • can improve selectivity

comparison electrochemistry and photochemsistry

• efficiency

How many electrons needed:

• catalytic quantities for initiation of radical chain process

• equivalent amounts for others (often excess electrons)

Photochemsitry

• energy transfer or electron transfer

electrochemsitry

• only electron transfer

reaction mechanism

electromediated synthesis

Target product is generated with an electron transfer via mediator

• in addtion to SET, the mediator allows to switch to other electron transfer technologies

  • SET

  • HAT

  • HYT (hydride transfer

• so electrochemistry is not a sole electron transfer technology

Advantages of electromediated synthesis

• allows switch from heterogenous to homogenous electron transfer

• rate determining step is shifted, leading to higher rates

  • eg. steric shielding of redox centre in proteins

• better energy efficiency: electromediators are usually activated at lower potentials

  • this allows midler conditions and higher selectivity (when sensitive FG’s are present)

• electrode passivation is avoided

  • = loss of electrode activity because a layer of product, impurities, gas bubbles or deposited material blocks the electrode surface

Separate or paired electrochemistry

Separate electrosynthesis

• product is generated at one electrode

• working electode + counter/sacrificial electrode

• maximum 100% with full conversion

Paired electrosynthesis

• product(s) is generate by contribution of 2 electodes

• 2 working electrodes

• max 200% with full conversion

• Examples

• parallel:

  • 2 different products max 200% cell conversion

• convergent

  • A is reduced an C is oxidized these react togehter to B

• Domino

  • A is oxidzed to B1 whcih reacts to B2 and reduced to C1

• Divergent

  • C1 is oxidized to C1* and C2 is reduced to C2*

  • A reacts with C1* to B and with C2* to C

  • glucose example (glucose is the common starting point but is in itself not reduced nor exidized, makes use of an electromediator

• Linear

  • A is oxidized to B and C is reduced to B

  • like water is oxidized to H202 at anode and O2 is reduced to H2o2 at cathode

name reactions 4

• Kolbe oxidation

• non-kolbe oxidation

• Shono oxidation

  

• Markó-Lam deoxygenation

Cost and sustainability

Cost

electrochemistry is inexpensive compared to oxidants and reductants

Sustainability

1. cheapest and most versatile redox reagent

2. can be combined with green electricity

3. reduction/ elimination of:

   1. toxic metal based oxidizing agents

   2. purification of spent reagents

4. milder conditions (p or T)

5. higher selectivity (avoids need for protection)

6. Universal reagent (cell potential can be tuned, and chemcial reagents work at fixed potential)

7. opens new synthetic pathways = less steps to end product

8. industrially scalable

   1. much more than photochemistry

chlor-alkali process

• Divided cell→ separate Cl2 and NaOH +H2

  • Cl2 + H2→ HCl: explodes under pressure or exposure to heat

  • 2NaOH + Cl2→ NaCl + NaOCl + H2O

    • Cl is oxidized and reduced

    • NaOCl is bleach → bad

Areas for improvement

• Selectivity anodic oxidation to Cl2

  • H2O can also be oxidized to O2

• Sluggish kinetic vor alkaline H2 evolution

• Membrane and anode degradation

• Design of electrolytic cell

• Energy demand: theoretical voltage = 2.1 V, practical voltage = 5 V

Improvements

• Use DSA = Dimensionally stable anode

  • RuO2 mixed with TiO2 supported by metallic Ti

    • Corrosion resistant + Ti support protects itself fur further corrosion by anodically forming an oxide layer

  • Ensures voltage reduction of >1 V + stable electrode performance

• Gas bubble effect

  • in the chlor-alkali process, gas bubbles are formed at the electrodes:

    • Cl₂ at the anode H₂ at the cathode

  • These gas bubbles can stick to the electrode surface.

  • When bubbles cover the electrode, they block the active catalytic sites, so less surface is available for reaction.

    • Bubbles also make ion/electron transfer harder, causing an extra ohmic drop and requiring a higher voltage.

  • This higher local voltage/overpotential can accelerate electrode corrosion.

  • Therefore, good electrodes should release gas bubbles quickly.

    • DSA electrodes help because they are:

    • very hydrophilic, so liquid wets the surface well

    • structured with a “mud-crack” morphology, helping bubbles detach faster

  • Faster gas bubble removal lowers the required cell voltage and improves efficiency.

• Cathode improvement

  • Cathode performs the hydrogen evolution reaction (HER): H2O +2é→ H2+OH-

    • But slow reaction in strongly basic solution

  • Oxygen-depolarized cathode (ODC)

    • Changes the cathode reaction

      • ½ O2 + H2O + 2é→ 2OH-

      • Requires less E than HER (O2 is fed through a gas diffusion electrode)

      • By adding O2 you ‘depolarize’ it because you remove high E barrier of forming H2 bubbles

      • No gas bubble effect at cathode (although H2 evolution can be a useful side product

• Bifunctional electrodes

  • Can facilitate 2 different chemical reaction

  • Can switch between HER and ODC (if H2 evolution is required or not)

• Coupling with CO2 reduction

  • Instead of HER counter reaction

  • Use CO2 reduction so instead of H2, CO2 reduction products are obtained alongside Cl2 and NaOH 

• Membrane improvement

  • New combined polymer layers with low electrical resistance, high ion-selective permeability and can work in corrosive electrolyte environments

Future of electrochemistry

Electrochemistry is gaining importance in pharma

• Drug companies are exploring electrochemistry as a cleaner and more efficient synthesis tool.

• It can replace chemical oxidants/reductants by using electrons directly.

• This can reduce waste and improve sustainability.

Main advantages for organic synthesis

• Electrons can act as “reagents”.

• Reactions can be more selective by controlling the potential.

• It can enable transformations that are difficult with classical chemistry.

• It fits well with green chemistry principles.

Artificial photosynthesis

• Electrochemistry can be coupled with light-driven processes.

• Sunlight can help drive oxidation and reduction reactions.

• Example: water oxidation at one side and CO₂ reduction at the other side.

• Goal: convert simple molecules such as CO₂ and water into useful fuels or chemicals.

Remote electrochemical plants

• Future electrochemical systems could be powered by renewable electricity, such as solar panels.

• This could allow small, decentralized chemical production units.

• Chemicals could be produced locally instead of in very large centralized plants.

Flow electrochemistry

• Flow reactors improve control over mixing, temperature, residence time, and current distribution.

• They are easier to scale by running longer or numbering-up reactors.

• Companies such as Creaflow develop scalable flow reactor technology.

Combination with other technologies

• Flow platforms can combine:

  • multiphase chemistry

  • photochemistry

  • electrochemistry

• This allows more efficient and flexible reaction development.

Application example: oxygenation reactions

• Electrochemistry can use simple inputs such as air, water, and light.

• This can make oxidation/oxygenation reactions more sustainable.

• Reactions can be catalyst-free, selective, and scalable.

Pharmaceutical production

• Electrochemistry in flow can be used to produce active pharmaceutical ingredients.

• Example shown: production of an anti-cancer drug/API in a flow process.

• This shows that electrochemistry is moving from academic research toward practical industrial application.