SN2, SN1, E1, E2 Reactions

ALL MY NOTES

Second Order Reaction because it depends on the concentration of 2 species

R = k[RX][-OH]

An SN2 is an example of what order of reaction and why?

Occurs in a single step

How many steps for an SN2 reaction

Mechanism for SN2 reaction

Lowering reactant energy or increasing transition-state energy

What increases the activation energy for an SN2 reaction? (Slows down reaction)

Increasing reactant energy or decreasing transition-state energy (pictured)

What decreases the activation energy for an sn2 reaction? (Catalyzes reaction)

A hindered, bulky substrate prevents easy approach of Nucleophile - D is impossible, C is sometimes possible

Steric effects in an SN2 reaction

Unreactive toward SN2 displacement due to steric factors

How do vinylic halides and aryl halides act in an SN2 reaction?

Nucleophile negative = neutral product

Nucleophile neutral = positive product

What are the products of a negative nucleophile or neutral nucleophile?

Any species, neutral or negative charge can act as nucleophile as long as it has unshared pair of electrons (MUST BE LEWIS BASE - donate e- to form covalent bond)

Describe a nucleophile in an sn2 reaction?

H2O

CH3O2-

NH3

Cl-

-OH

CH3O-

I-

-CN

-SH

List these 9 nucleophiles from weakest to strongest:

-SH, CH3O-, NH3, Cl-, I-, H2O, CH3O2-, -CN, -OH

As you move down a column in periodic table

EX: HS more nucleophilic than OH > I- > Br- > Cl-

Nucleophilicity increases as you move?

Usually carried out in basic conditions

SN2 reactions are usually in what type of conditions?

Weak bases are best leaving group because they best stabilize the negative charge

Describe the best kind of leaving group for SN2 reactions

(-OH, -NH2, -OR) bad leaving groups

F- (very weak)

Cl-
Br-

I-

TosO-

List the following leaving groups by reactivity going worst to best:

I-, Br-, -OH, TosO-, -NH2, F-, -OR, Cl-

alkyl fluorides, alcohols, ethers, and amines

What types of molecules typically do not do SN2

Favor polar aprotic solvents - have no -OH or -NH — solvate metal cations, not Nucleophile anions

Describe the best solvent for an SN2 reaction

CH3OH

H2O

DMSO

DMF

CH3CN

HMPA

List the solvents from worst to best for an SN2 reaction:

DMF, HMPA, CH3OH, CH3CN, H2O, DMSO

Protic solvents (contain -OH or -NH) like methanol or ethanol slow down SN2 by solvation of nucleophile (H-bond to it)

Describe the worst kind of solvents for an SN2 Reaction

First order reaction

R = k[RX]

The rate-limiting step does not involve the nucleophile

An SN1 reaction is what type of order? What is its equation?

Has 3 steps

1. Spontaneous dissociation of alkyl bromide (slow rate-determining step)

2. Carbocation reacts with nucleophile in fast step to get protonated alcohol

3. Loss of proton = neutral alcohol product

Mechanism for SN1 reaction

Racemic mixture (not usually 50:50 because of ion pairs — still loosely associated thus blocking rxn on one side (prefers inversion, attacking from backside)

Describe the products of an SN1 reaction… why does this happen what does it prefer?

More stable carbocation formed = faster SN1 rxn

tertiary > secondary > primary (never occurs)

Describe the substrate for an SN1 reaction

Allyl (2 resonance structures) and benzyl (5 resonance structures) cations are unusually stable — increasing rate of rxn

Allyl and benzyl cations in Sn1 reaction do what to the reaction rate?

List carbocations in order of increasing stability (include primary allyl and primary benzyl)

Primary allylic and primary benzylic substrates are also involved in SN2 rxns

What is important to remember about primary allylic and primary benzylic substrates?

-OH

Cl-

Br-

I- = TosO-

H2O

List the following in order of increasing leaving group reactivity for SN1 reactions:

Br-, I-, H2O, -OH, Cl-, TosO-

Sn1 - works best for tertiary alcohols because they give the most stable carbocation intermediates

what mechanism type is involved in the conversion of alcohols to alkyl halides?

Nucleophile does not matter, can’t affect reaction rate in SN1

What role does the nucleophile play in an sn1 reaction?

Neutral or acidic conditions

What are the best conditions for an SN1 reactions?

Ethanol

40% H2O/60% ethanol

80% H2O/20% ethanol

H2O

List solvent reacitivty from least to greatest for sn1 reaction:

H2O, 80% H2O/20% ethanol, ethanol, 40% H2O/60% ethanol

Favor polar solvents - lower transition state energy to carbocation by solvation

vs less polar solvents like ethers or CHCl3 (chloroform) are slower

What type of solvents favor sn1 reactions?

Protic solvents lower the ground state of the nucleophile due to solvation

Why do SN2 reactions dislike polar protic solvents?

E1 reaction mechanisms

E2 reaction mechanisms

E2

Examples: NaH, DBN, DBU

Strong base/weak nucleophile

For primary: E2 (major) or SN2

secondary and tertiary: E2

Examples: -OH, CH3O- (methyl oxide), EtO- (ethyl oxide)

Strong base/strong nucleophile

For primary and secondary: SN2

Tertiary: SN1

Examples: I-, Br-, Cl-, RS-, HS-, RSH, H2S

Weak base/Strong nucleophile

no reaction for primary or secondary…

tertiary: SN1 or E1

Examples: H2O, MeOH, EtOH

Weak base/Weak nucleophile

methyl substrate and bulky base = SN2

primary, secondary, and tertiary substrate and bulky base = E2

Example of bulky base: tertBuO-

Bulky Base and primary, secondary, or tertiary substrate

methyl substrate + strong base = SN2

primary substrate + strong base = SN2/E2

secondary substrate + strong base = E2 (Favors)/SN2

tertiary substrate + strong base = E2

Examples of strong bases = -OH, Ch3O-, EtO-

Strong base and primary, secondary, or tertiary substrate

Methyl/primary/secondary substrate + aprotic solvent = SN2

tertiary substrate + aprotic solvent = SN1/E1
Examples of aprotic solvents = DMF, DMSO, I-, CN-, RS-

Aprotic solvent and primary, secondary, tertiary substrates

methyl, primary substrate + protic solvent = SN2

secondary substrate + protic solvent = SN1/E1 (favors)/SN2

tertiary substrate + protic solvent = SN1/E1

Examples of protic solvents: H2O, MeOH

protic solvent plus primary, secondary, or tertiary substrate…

second order

rate = k[RX][Base]

E2 is what type of reaction order?

Leaving group and H must both be axial for anti periplanar elimination to occur

E2 in cyclohexane rings