Substitution And Elimination Flashcards
Sn1 reactivity (from most reactive to least)
Based on carbocation stability:
3° benzyl
3° allyl
2° allyl
3°
1° allyl
2°
1° and methyl cannot undergo Sn1 reaction
Sn1 reaction product stereochemistry
Give racemic mixture of enaantiomers —> this is due to nucleophile being able to attack from either side
Do Sn1 reactions involve rearrangement?
YES, because they involve carbocation intermediates, the carbocation can rearrange to give the most stable carbocation intermediate
What is the rate of Sn1 reactions?
Rate = k[electrophile]
What is the rate for Sn2 reactions?
Rate = k[electrophile][nucleophile]
Sn2 reactivity (from most reactive to least reactive)
Methyl LG
1° LG
2° LG
Bezyls and allyls CAN undergo Sn2 depending on the nucleophile
3° LG cannot undergo Sn2 reactions
Sn2 stereochemistry
Inversion of stereochemistry due to backside attack
what mechanism would you use if a 1° carbon is bonded to the leaving group?
Sn2 or E2
what mechanism would you use if a 2° carbon is bonded to the leaving group?
Sn1, Sn2, E1 or E2
what mechanism would you use if a 3° carbon is bonded to the leaving group?
Sn1, E1 or E2
1° bonded to leaving group
strong nucleophile or weak base
Sn2
1° carbon bonded to leaving group
strong nucleophile or strong base
Sn2 (major)
E2 (minor)
1° carbon bonded to leaving group
strong, bulky base
E2
2° carbon bonded to leaving group
weak nucleophile or weak base
Sn1 or E1
2° carbon bonded to leaving group
strong nucleophile or weak base
Sn2
2° carbon bonded to leaving group
strong nucleophile or strong base
E2 (major, trans)
Sn2 (minor)
2° carbon bonded to leaving group
strong bulky base
E2
3° carbon bonded to leaving group
weak nucleophile or weak base
Sn1 or E1
3° carbon bonded to leaving group
strong nucleophile or weak base
Sn1
3° carbon bonded to leaving group
strong base
E2
3° carbon bonded to leaving group
strong, bulky base
E2 (non-zaitsev)
What are the three trends when ranking strength of nucleophiles?
1) Negative charges increase nucleophilicity
2) Nucleophilicity increases going left across a row
3) Moving down a column, nucleophilicity depends on the solvent
Strength of nucleophiles in protic solvents:
Increases going down a column this is because protic solvents form a “hydrogen bond web” and solvate the nucleophile, making it harder for the nucleophile to attach —> a larger atom will break through the web better than a small, solvated atom
Size matters for protic solvents
Strength of nucleophiles in aprotic solvents:
Decreases going down a column because aprotic solvents do not interact with the nucleophile —> only concentrated, negative charges matter in aparotic solvents
Strength of nucleophile going across a row:
Increases going left across a row (becomes more basic)
Ex: F- is a weaker nucleophile than NH2-
In nucleophilic addition reactions, EWG substituents (increase/decrease) the positive charge on the carbonyl carbon, thus (increasing/decreasing) reactivity
Increase
Increasing
An EWG pulls the electron density away from the carbonyl carbon, thus making the reactivity of the nucleophile and carbon greater
In nucleophilic addition reactions, (aldehydes/ketones) are more reactive
Aldehydes
In nucleophilic addition reactions, the carbon of the carbonyl group is _____________
Electron deficient- the electronegative oxygen pulls electron density away from the carbonyl carbon
In nucleophilic addition reactions, bulky substituents attached to the carbonyl carbon will (increase/decrease) steric hinderance involved with nucleophilic attack, thus (increase/decreasing) reactivity
Increase
Decreasing
General rule for determining aprotic solvents:
Aprotic solvents lack an acidic proton, if the solvent lacks hydrogen directly bonded to oxygen or nitrogen, it can be considered aprotic
What solvent should be used for Grignard reagents?
Grignard reagents are highly basic compounds that can act as a nucleophile to attack carbonyl-containing compounds. Aprotic solvents should be used with Grignard reagents because in protic solvents, the Grignard reagent will act as a base to deprotonate the solvent rather than attacking the nucleophile
strong/weak nucleophile/base NaSCH3
- strong nucleophile weak base
strong/weak nucleophile/base NaOH
- strong nucleophile strong base
strong/weak nucleophile/base tBu-OK
strong base weak nucleophile
strong/weak nucleophile/base NaSH
weak base strong nucleophile
strong/weak nucleophile/base NaCN
weak base strong nucleophile
strong/weak nucleophile/base H2O
weak base weak nucleophile
strong/weak nucleophile/base NaH
strong base weak nucleophile
a strong base would be able to ____ H atom easily
accept
strong/weak nucleophile/base EtOH
weak nucleophile weak base
strong/weak nucleophile/base H2S
strong nucleophile weak base
strong/weak nucleophile/base MeOH
weak nucleophile weak base
strong/weak nucleophile/base NaN3
strong nucleophile weak base
strong/weak nucleophile/base KOH
strong nucleophile strong base
strong/weak nucleophile/base KOH
strong nucleophile strong base
strong/weak nucleophile/base NaI
strong nucleophile weak base
strong/weak nucleophile/base NaOMe
strong nucleophile strong base
