Topic 1: Nucleophilic Substitution Flashcards
difference between SN1 and SN2
SN1: unimolecular, 2 steps
SN2: bimolecular, single step
properties of SN2 reaction
for primary and secondary carbon
configuration of carbon will get inverted
rate depends on:
- steric effects of electrophiles
- nucleophilicity of nucleophiles
- leaving ability of leaving groups
- polarity of solvents
how does steric effects affect rate of SN2
rate increases when C has less bulky groups
Nucleoside needs to do backside attack > harder to attack if blocked by bulky groups
how does electronic effects of electrophiles affect rate of SN2
pi electron cloud of C=C bonds block Nu approach > rate decrease
allylic and benzylic C-X bond promotes SN2
- pi electron of C=C interacts with transition state > partial electron density when Nu attacks shifts to pi system > spreads electron density > stabilise transition state > rate increase
relationship between stabilisation of transition state and rate of SN2
greater stabilisation of transition state > lower Ea > higher reaction rate
what is required for SN1/E1 to take place
both require two step reaction where first step forms carbocation intermediate > require stable carbocation, if dont have then reaction is unlikely
when is elimination favoured over Nu substitution
when using strong bulky base
E2 favoured with strong base while E1 favoured with weak base
steric hindrance promotes elimination
what is beta hydrogen
H atom attached to beta carbon (carbon next to the carbon bearing the leaving group) > a must have for elimination reactions to take place
why does nucleophilicity in solution increase down the periodic table
ionic radius increases down the group > more diffused electron cloud > form bonds more easily with electrophile
difference between polar aproptic and polar protic solvents
aproptic: solvents that are polar but no H atoms available for H bonding > favours SN2 and E2 by keeping nucleophiles “free” and reactive
protic: solvents that have H atom bonded to electronegative atom to form H bond > favours SN1 and E1 by stabilising carbocation intermediate
difference in nucleophilicty in halide ions in solution and in gas phase
in solution: F- least bc its the smallest > highest charge density > attract more polar solvent molecules to form a “shell” > F- harder to attack electrophiles bc “blocked”
in gas: F- strongest bc w/o solution, nucleophilicity follows basicity > F- strongest base
when is Gabriel primary amine synthesis using phthalimide used
to prevent multi substitution to give primary amine
phthalimide has strongly stabilised N due to resonance > decrease nucleophilicity > only undergo one alkylation reaction unlike NH3
how to determine if leaving group is a good leaving group
stable anions > good leaving group
resulting anionic charge can be stabilised > good leaving group
leaving group small and too basic > want to hold onto protons > bad leaving group (eg OH)
how is alcohol converted into tosylates
OH poor leaving group > converted into -OTs (tosylate) using TsCl and base (usually pyridine)
tosylates are good leaving groups > now can undergo SN2 or E2 reactions
difference between R-OH to R-Cl via SOCl2 using pyrimidine vs Et2O as solvent
pyrimidine: inversion of configuration
Et2O: retention of configuration
how to convert R-OH to R-Br
using PBr3
only effective for primary and secondary alcohols
- substitution at P of Br
- bromination via SN2 reaction
how is R-OH converted to R-OCOR’ (ether) via mitsunobu reaction
using PPh3 and DEAD
- PPh3 reacts with DEAD to generate reactive phosphonium intermediate > activates hydroxyl group of R-OH
- second alcohol R’OH acts as Nu and attacks activated OH > form ether with inversion of stereochemistry
properties of SN1 reaction
causes C to lose chirality
leaving group departs first > carbocation formed > Nu can attack from either side of the plane with equal probability > racemic mixture > loss of chirality
structural influence of electrophiles on rate of SN1
reaction rate determined by stability of carbocation
tertiary C most reactive cause most EDG > stabilise positive charge
effect of nucleophilicity of nucleophiles on rate of SN1
not important as Nu not involved in rate determining step
effect of leaving ability of leaving groups on rate of SN1
similar trend as SN2
H2O can be good leaving group in SN1 under acidic conditions
how does solvent effects affect SN1 and SN2 differently
SN1: solvent affects formation and stabilisation of carbocation intermediate
SN2: solvent affects transition state
