Nucleophilic substituions = SN1 and SN2 Flashcards
nucleophile always attacks the ______
electrophile
Explain what the Transition state is:
theoretical representation of the high energy point between starting materials and products. It does not physically exist
(a moment when a bond is forming and breaking)
How many steps in the Sn2 reaction?
1 with NO intermediate formation
What is SN2?
Substitution Nucleophilic Bimolecular reaction
Bimolecular reactions
two species are involved in the rate determining step (slowest step of a reaction)
What is involved in the rate-limiting step?
BOTH - Nucleophile and electrophile
Transition state: bond to the nucleophile (hydroxide) is partially ______ and the bond to the leaving group (bromide) is partially _______
formed
broken
Omeprazole is a….
proton pump inhibitor that decreases the amount of acid produced in the stomach
Factors Affecting SN2 reaction: nucleophile
1) strength of nucleophile
2) Nucleophilicity increases
3) Nucleophilicity decreases
4) Bulkiness of the nucleophiles
define Basicity
the equilibrium constant for abstracting an acidic proton;
forms a new bond to a proton, it has reacted as a base
define Nucleophilicity
the rate of attack on an electrophilic carbon atom;
forms a new bond to carbon, it has reacted as a nucleophile
- strength of nucleophiles
Species with negative charge: stronger nucleophile than a similar neutral species. Base is a stronger nucleophile than its conjugate acid
- 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)
- Nucleophilicity increases
down the periodic table, following the increase in size and polarizability (more electrons far from the nucleolus)
e- are more ______ held > move more freely toward a +ive charge > stronger bonding, enhancing atom’s ability to begin to form a bond at a relatively long distance
loosely
- Bulkiness of Nucleophiles
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
What is a steric hindrance?
he slowing of chemical reactions due to steric bulk
manifested in intermolecular reactions, whereas discussion of steric effects often focus on intramolecular interactions
exploited to control selectivity, such as slowing unwanted side-reactions
Protic solvents meaning and characteristics?
OH/NH groups (i.e. alcohols)
H-bonds to negatively charged nucleophiles
Very good in solubilising reagents
Aprotic solvents meaning and characteristics?
without OH/NH groups (i.e. hexane).
Enhance nucleophilicity of anions
Anions are more reactive
Relatively weak solvating ability
POLAR aprotic solvents: no OH or NH
Enhance solubility
Acetonitrile, dimethylformamide (DMF), acetone, and dimethyl sulfoxide (DMSO)
From alcohol to DMSO often enhances the rate of an SN2 reaction
Reverse the nucleophilicity order (F->Cl-…)
Factors Affecting SN2 reaction: substrate
Leaving-Group Effects on the Substrate
Polarise C-X bond (making the carbon atom electrophilic)
Leaves with the pairs of electrons
Factors Affecting SN2 reaction: substrate
name 2
- Electron withdrawing: polarise the carbon atom and stabilises the negatively charged transition state. Halogen, oxygen, nitrogen, sulphur
- Stable once has left:
weak base (i.e. Cl-, Br-, I-), so conjugate bases of strong acids (i.e. HCl, HBr, HI)
______ bases are poor leaving groups
strong
(-OH/-NH2)
neutral molecules can be good leaving groups example =
H2O, alcohols, amines
+NMe3 > TsO- > I— > Br — > +OH2 > Cl— > F— > OH—
REMEMBER - not only halogens are _____ leaving group and not only ____ species are formed
good
negative (-ive)
the Sn2 reaction is highly dependant on the structure of the ________
electrophile
steric_____ of the electrophile influences the mechanism of the reaction
bulk
different names fir the steric effects on the substrate:
a) Methyl derivative - 3H group
Very Fast
b) Primary Carbon - 1 diff group + 2H
Fast
c) Secondary Carbon - 2 diff group +1H
Slow
d) Tertiary Carbon - 3 diff group
SN2 Not Possible!
the more different groups are in the compound; the ______ the reaction.
slower
To 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
Reaction-rate:
does not depend on the concentration of the nucleophile but depends only on the concentration of the substrate (electrophile)
What type of reaction is SN1?
Substitution Nucleophilic, Unimolecular reaction
Unimolecular reactions:
only one specie is involved in the rate determining step (defined as the slowest step of a reaction)
steps of SN1
3 steps
Step 1: Formation of carbocation (rate limiting)
Step 2: Nucleophilic attack on the carbocation
Final Step: Loss of proton to solvent
what type of reaction is an SN1 reaction?
racemisation
Factors Affecting SN1 reaction: substrate = Substituent effect
EASIER the formation of the carbocation intermediate, the faster the SN1 The MORE STABLE the carbocation, the faster the SN1
➜Lots of electron density
+ve charge stabilised
➜low electron density
+ve charge poorly stabilised
bulk effects in SN1
tertiary - fast SN1
Secondary Intermediate
Primary - SN1 Not possible
Resonance stabilisation
carbocation promotes the SN1 reaction
Leaving-Group Effects: weak base
very stable after it leaves with the pair of electrons that bonded it to carbon
Protic solvent
polar solvents stabilise ions, therefore favour SN1. H2O, alcohols
Carbocations often rearrange to form more ______ carbocations
stable
The rearrangement could involve a –CH3 group (movement of a methyl group)
to give a ______ ______
Methyl shift
Test yourself:
One step
Favours strong nucleophiles
Racemizes stereochemistry
Could involve carbocation rearrangements
Has a carbocation intermediate
Best in protic solvents (Water, alcohols..)
Two steps
Inverts stereochemistry
Best in aprotic solvents
