EXAM 3 Electrophilic Aromatic Substitution

Reagents for EAS

There are multiple different reagents these are the ones you would start off by putting on the Benzene ring.

Reagent for Chlorine

Cl₂/FeCl₃ = Cl+

Reagent for Bromine

Br₂/FeBr₃ = Br+

Reagent for Iodine

I₂/H₂O₂ or Cu²+ = I+

Reagent for Nitration

HNO₃/H₂SO₄ = NO₂+

Reagent for Sulfonation

SO₃/H₂SO₄ = SO₃H+

Friedel-crafts alkylation of benzene

CH₃Cl, AlCl3 = CH₃

Remember about major and minor products how can they be distinguished, Hint: Think zaitsev's rule

Products can be done with carbocation rearrangement

Friedel-Crafts Acylation

Reagent Pathway to make a Diazonium salt

Everything is on Benzene!!!

1. HNO₃/H₂SO₄ = NO₂

2. H₂/Pd or Pt = NH₂

3. NaNO₂/HCl/0ºC = N Triple Bond N or Diazonium salt

Iodine on the “wheel of doom”

KI = I

Hydrogen on the “wheel of doom”

H₃PO₂ = H

OH on the “wheel of doom”

H₂O/H+ = OH

C Triple bond N on the “wheel of doom”

CuC Triple Bond Nitrogen

Chlorine on the “wheel of doom”

CuCl = Cl

Bromine on the “wheel of doom”

CuBr = Br

Fluorine on the “wheel of doom”

HBF₄ = F

Side Chain Oxidation Reagent

K+MnO₄-/OH-/Heat

• only works in the presence of Hydrogens off of the alpha carbon!

• creates carboxylic acids

Reagent for converting a carboxylic acid to an acyl halide

SOCl₂/ET₃N (Tri-ethylamine)

Strong Activators

NH₂, OH, OCH₃ (lone pair atoms)

• ortho/para director

• speed up EAS

• highest

Weak activators

alkyl groups (ortho/para)

Weak deactivators

Halogens (F, Cl, Br, I)

• ortho para directors

Strong deactivators

• multiply bonded atoms

• meta director

• weakest

Nucleophilic Aromatic Substitution (NAS)

Replacement of a leaving group on an aromatic ring by a strong nucleophile. Usually takes place by an addition-elimination mechanism or by a benzyne mechanism.

NABH₄ H- reacts with?

Selective - Aldehydes and Ketones!!!!!!

LiAlH₄ can react with?

Non-selective = Reduces everything!!!

What's the purpose of a Ketals/acetals

To protect Ketones and Aldehyde functional groups

Product when LiAlH₄ reacted with an Amide

1º Amine/It works by having the Oxygen bind with the Aluminum make it the leaving group

NaBH₄ has to be done what again

Repeated if used on Aldehydes and Ketones

Benzyne Reagents

NH₂-/NH₃ (Liquid death) The ONLY REAGENT FOR BENZYNE

NaBH₄ is NOT powerful enough to reduce carboxylic acids, esters, or amides

So you can selectively reduce a ketone or aldehyde in the presence of one of these groups.

carboxylic acid

acid halide (chloride)

anhydride

ester

amide

General mechanism of carboxylic acid derivatives with strong nucleophiles

• Negative attacks C=O carbon

• Texas carbon

• O^- swings down and kicks off the leaving group

• Reform C=O bond

• Replace the leaving group with the reagent

• Leaving group floats in parentheses

most reactive to least reactive…

acid halide > anhydride > ester > amide

T or F: reactions that turn more reactive derivatives into less reactive ones are ok!

TRUE

what does hydrolysis mean or saponification?

water breaking

ester hydrolysis

What is the Gabriel Synthesis?

Used to make primary (1°) amines

ortho/para directors

• -NH₂, -OH, -OCH₃, -F, -Cl, -Br, -I

Groups with lone pair atoms directly attached to benzene cause EAS to occur

meta directors

• -C=O, -SO₃H, -C triple bond N, -NO₂:

Groups with a multiply-bonded atom directly attached to benzene cause EAS to occur

what happens when groups have about (~) equal activating power?

let steric hinderance be your guide

what happens when you have conflict between 2 groups

determine which is stronger (SWWS)

why do ortho/para directors work?

resonance

T or F: start an attacker on a negative thing and end on a positive

TRUE

what happens when you have 2 or more strong deactivators in an EAS rxn?

NO REACTION!

T or F: activators make the attacker more negative

TRUE

what mechanism looks like a carousel?

Diels-Alder Reaction

T or F: esters are more reactive than amides

TRUE

T or F: a successful haloform reaction produces a purple precipitate

FALSE

T or F: the 1st step of electrophilic aromatic substitution (“door opening”) is faster than the 2nd step

FALSE

what does “Orange Mice Sleep Gently After Parties” mean?

oxalic, malonic, succinic, glutaric, adipic, and pimelic

T or F: The product of a malonic ester synthesis is… malonic ester

FALSE

T or F: NaBH4 will reduce carboxylic acids but not ketones

FALSE

T or F: The side chain of ter-butylbenzene is easily oxidized by KMnO4/OH-

FALSE

T or F: The amino acids in proteins are connected via amide bonds

TRUE