CH 8: Substitution and Elimination Reactions of Alkyl Halides

What makes a good leaving group?

1) weak conjugate base of strong acid

3) weaker base than the nucleophile/base

If you have a bad leaving good, what can you do?

convert it into their conjugate acid through addition of a strong acid (or Lewis acid)

What reaction mechanism does polar aprotic solvents favor?

S_N2

alkyl halides or haloalkane

R₃ — X (an alkane connected to a halogen)

aryl halides

an aromatic ring connected to a halogen

vinyl halides

an alkene connected to a halogen

for alkyl halides, the bond length _________ as a ______ atomic mass atom is attached to the molecule.

increases, higher

for alkyl halides, the most polar molecule is attached to a ______ electronegative atom.

higher

Radical Chain Mechanism (3)

Initiation, Propagation, and Termination

Initiation

1) With some light or heat, X₂ splits homolytically and produces 2 radicals (atoms or molecules w/ unpaired e^-).

What happens in the 1st propagation step?

Halogen radical bonds with one of H atom’s e^- (of the reactant).

What happens in the 2nd propagation step?

In the 2nd step, another X₂ homolytically splits again. A halogen radical bonds with the reactant radical.

Termination

Three products form.

• Two X radicals bond and molecular halogen forms.

• Halogen radical bonds with reactant radical. Haloalkane forms.

• Reactant radical bonds with another reactant radical and a new product forms.

Of the three steps of radical chain mechanism, the slowest or rate-determining step is….

propagation

In order to get monosubstituted chloromethane, one way is…

use a higher concentration of alkane in comparison to chlorine

Who is more selective? Chlorination or bromination?

bromination

What are two reasons that alkyl halides undergo substitution and elimination?

Since the halogen is a e- withdrawing group, it creates a partial positive charge on the alpha carbon, making it more susceptible for nucleophilic attack.

What are the 2 possible substitution mechanism?

S_N2 and S_N1

What happens in S_N2 or bimolecular nucleophilic substitution reaction?

• one-step (concerted) mechanism

  • leaving group leaves

  • nucleophile attacks

  • happening at the SAME time.

What happens in S_N1 or unimolecular nucleophilic substitution reaction?

• multi-step mechanism

• leaving group leaves

• carbocation forms

• nucleophile attacks

Why does the nucleophile attack from the back-side?

1) Front-side is e^- dense.

2) Homo of nucleophile can flow to the lumo of the electrophile.

What happens to the chiral carbon of the S_N2?

The reaction is stereospecific, so the alpha carbon (reaction site) will undergo an inversion of configuration.

What prevents S_N2 from happening? What does that mean?

Too much steric hinderince meaning more branching on the alpha and beta carbons of alkyl groups result in a lower rate of rxn.

What determines or influences the strength of the nucleophile?

1) charge

2) resonance

3) electronegativity

4) atomic mass

5) steric hinderance

What makes a strong nucleophile?

1) anion

2) no resonance

3) low electronegativity

4) bigger atomic mass

5) less hindered

What is the PT pattern for a strong nucleophilicity?

Right to Left and Top to Bottom

What are the 8 strong nucleophiles?

chloride ion (Cl^-), bromide ion (Br^-), iodide ion (I^-), HS^-, RS^-, HO^-, RO^-, and N(triple bonded)C^-

What are the 4 polar aprotic solvent?

DMF (O(double bonded)C(bonded to)H and N(bonded to) R₁ and R₂, DMS (sulfide), DMSO (O(double bonded)S(bonded to)R₁ and R₂, and acetone (ketone)

How can you identify a protic solvent?

1) solvent that can donate protons

2) Does it have a OH or NH?

What is the requirements of a S_N2 reaction?

strong nucleophile and polar aprotic solvent

What is the rate-determining step in a S_N1 reaction?

carbocation intermediate

What is the relationship btwn the carbocation intermediate and the rate of S_N1?

directly proportional, so the more stable the carbocation intermediate, the faster the reaction

What is the first question you should ask about the rxn?

The func. (base or nucleophile/strong or weak/less bulky or bulky) of the reagant

What is the second question you should ask about the rxn?

The type of substrate (1^°, 2^°, or 3^°) and the expected mechanism (S_N1, S_N2, E1 or E2)

What is the third question you should ask about the rxn?

The regiochemical and stereochemical requirements (stereocenter inversion, racemization, antiperiplanar, Zaitsev, and Hoffman)

Starting with the 1st question, what kind of reagants promote S_N1, S_N2, E1 and E2?

S_N1: weak nucleophile

S_N2: strong nucleophile

E1: weak base

E2: strong base

LDA (Lithium Di-isopropyl Amide) - type of B and Nu

SB/WNu

t-buOK - type of B and Nu

SB/wNu

HO^-/^-OH - type of B and Nu

SB/SNu

MeO^-/^-OMe/H₃CO^-/^-OCH₃ - type of B and Nu

SB/SNu

EtO^-/^-OEt - type of B and Nu

SB/SNu

I^-, Cl^-, and Br^- - type of B and Nu

WB/SNu

Why are I^-, Cl^-, and Br^- weak bases?

they are conj. bases of strong acids

RS^- and HS^- - type of B and Nu

WB/SNu

RSH and H₂S - type of B and Nu

WB/SNu

H₂O - type of B and Nu

WB/WNu

MeOH/CH₃OH - type of B and Nu

WB/WNu

EtOH/CH₃CH₂OH/ - type of B and Nu

WB/WNu

What are the (4) common strong bases used in ochem?

RO^- (oxygen chain), NH₂^-, LDA (lithium di-isopropyl amide), and t-BuO^-

What are the (13) strong nucleophiles?

I^-, Cl^-, Br^-, HS^-, RS^-, HO^-, RO^-, NC^-, RCOO^-, R₃P, R₂NH₂, NH₃, and R₂S (RSH)

What are the (3) weak nucleophiles?

H₂O, ROH, and F^-

SB/WNu and 1° - type of mechanism

E2

SB/SNu and 1° - type of mechanism

S_N2

WB/SNu and 1° - type of mechanism

S_N2

WB/WNu and 1° - type of mechanism

NR

SB/WNu and 2° - type of mechanism

E2

SB/SNu and 2° - type of mechanism

E2

WB/SNu and 2° - type of mechanism

S_N2

WB/WNu and 2° - type of mechanism

S_N1 or E1, heat is the determinator

SB/WNu and 3° - type of mechanism

E2

SB/SNu and 3° - type of mechanism

E2

WB/SNu and 3° - type of mechanism

S_N1

WB/WNu and 3° - type of mechanism

S_N1 or E1, heat is the determinator

S_N2 - regioselectivity/stereoselectivity

concerted (one-step) mechanism, so there is a single product and an inversion of configuration at the alpha-carbon

S_N1 - regioselectivity/stereoselectivity

a multi-step mechanism, so the most substituted carbocation will form and the chiral carbon will lead to 2 products (R and S)

E2 - regioselectivity/stereoselectivity

- concerted (one-step) mechanism, so the alkenes will form from having beta-hydrogen that is antiperiplanar to the LG.

- bulky bases —> Hoffman product (or less substituted alkene)

- less bulky bases —> Zaitsev product (or most substituted alkene

- trans disubstituted alkene are favored over cis disubstituted alkene

- E trisubstituted alkene are favored over Z trisubstitutted alkene

E1 - regioselectivity/stereoselectivity

- a multi-step mechanism, so the most carbocation will form and the alkenes will form from having beta-hydrogen

- major product —> most substituted alkene

Stereoselective rxn

one major and one minor product formed

stereospecific rxn

only one product formed