SN2 reaction & SN1 Flashcards
SN2 reactions
Nucleophile approaches electrophile from the opposite side of the molecule to the leaving group
Transition state
- Theoretical representation of the high energy point between starting materials and products. It does not physically exist
Why SN2
Reaction occurs in one step, with no intermediates formation
Bimolecular reactions
Two species are involved in the rate determining step defined as the slowest step of a reaction
What is involved in rate limiting step
- Electrophile and nuclephile
Transition state
- Bond to the nucleophile (hydroxide) is partially formed, and the bond to the leaving group (bromide) is partially broken
SN2 on Alkyl Halide
- Nucleophiles convert alkyl halides to a wide variety of functional groups
Omeprazole
Proton pump inhibitor that decreases the amount of acid produced in the stomach
Factors Affecting SN2 reaction
- Strong nucleophile reacts faster in SN2 reaction
- Species with negative charge
- Base has a stronger nucleophile than its conjugate acid
Basicity
Equilibrium constant for abstracting an acidic proton forms a new bond to a proton, it has reacted as a base
Nucleophilicity
Rate of attack on an electrophilic carbon atom forms a new bond to carbon, it has reacted as a nucleophile
Trend of Nucleophilicity
- Decreases from left to right in the periodic table, following the increase in electronegativity
- tightly held non-bonding electrons that
are less reactive toward forming new bonds - Increases down the periodic table, following the increase in size and polarizability
An increase in nucleophilicity
- More loosely held, can move more freely toward a positive charge, resulting in stronger bonding, enhancing the atom’s ability to begin to
form a bond at a relatively long distance
Nucleophile
- An ion or a molecule must get close to a carbon atom to attack it
- Bulky groups on the nucleophile hinder this close approach, slow the reaction rate
Steric hinderance
- Slower SN2 reaction in larger molecules e.g stronger base means weaker nucleophile
- Weaker base means stronger nucleophile
Solvent effect on Nucleophilicity
Protic solvent
- OH/NH groups H bonds to negatively charged nucleophiles very good in solublising reduce nucleophilicity small anion
- Not good for SN2 reaction
Aprotic solvent
- Without OH/NH enhances nucleophilicity
- Anions are more reactive with weak solvating
Polar aprotic solvent
- OH or NH enhances solubility
- Enhances SN2 REACTION SOLUBLISE WITH REAGENT AND DOESNT FORM HYDROGEN BOND
Polar aprotic solvent
- OH or NH enhances solubility
- Enhances SN2 REACTION SOLUBLISE WITH REAGENT AND DOESNT FORM HYDROGEN BOND
Electron withdrawing
- Polarise the carbon atom stablise the negatively charged transition state, Halogen, oxygen, nitrogen and sulpher
- Stable once left weak base conjugate strong acid
- Strong base poor leaving group OH
- +NMe3 > TsO— > I— > Br — > +OH2 > Cl— > F— > OH- order of leaving group strength
Sn2 reaction with electron deficient molecule
electron deficient (positive) nitrogen gains a pair of electrons from the broken bond, forming a stable
neutral molecule
Factors that effect Sn2 reaction methyl groups
- Steric bulk of the electrophile influences the mechanism of the reaction
- 3 methyl groups mean that there is more steric hinderance less acess to carbon
Inversion of configuration
- When the electrophile attacks from the backside it causes the conversion srom S to R visa versa
Why are SN2 reactions important
Avoid side-effects from unwanted isomers you recommend to a drug development researchers that only the RR isomer of Labetalol should be available
Sn1 reaction rate
- Doesn’t depend on conc of nucleophile but depends on conc of the electrophile
- Substitution nucleophilic unimolecular reaction
Sn1 reaction rate
- Doesn’t depend on conc of nucleophile but depends on conc of the electrophile
- Substitution nucleophilic unimolecular reaction
Unimolecular reaction
- Only one specie is involved in the rate determining step
Substituent effect
- The EASIER the formation of the carbocation intermediate, the faster the SN1
- The MORE STABLE the carbocation, the faster the SN1 more donation the electrons to the central positive
Sn2 ease of reaction
- Lots of electron density +ve charge stabilised
- Low electron density +ve charge poorly stabilised
- Tertiary is fast and primary is not possible
Steps of Sn1 reaction
- Formation of carbon cation
- Nucleophilic attack on the carbocation
- Loss of proton to solvent
Racemisation reaction
- 50% of S and 50% of R
- Attacted by 2 sides mixture around the chiral carbon
Resonance stabilisation
- Carbon cation promotes the Sn1 reaction
- ## Leaving groups effect - weak base vaey stable after it leaves with pair of electrons bonded to carbon
Protic solvents
- Polar solvents stabilise ions, therefore favour SN1. H2O,
alcohols
Methyl shift can occour
- More stablised as tertiary carboncation is more stable
