Aromatic chemistry

From closest to furthest to a given substituent, what are the names given to the carbons on a benzene ring?

ipso, ortho, meta, para

What are the four criteria an aromatic compound must satisfy?

• planar

• fully conjugated

• cyclic

• Follows Huckel’s rule; has (4n)+2 π electrons

How to determine Huckel’s rule

every double bond has 2π electrons. n= any number

eg. with benzene: 3db therefore 6π electrons, 6= (4×1)×2

a) Is benzene stable and b) why and c) what does this mean for electrophiles?

a) yes very

b) delocalised π bonds

c) must be very strong and reaction must be with Lewis acid

electrophilic aromatic substitution mechanism

What is the difference between a transition state and an intermediate?

A transition state unlike an intermediate cannot be spectroscopically observed of isolated and is higher in energy

How is benzene sulfonated: a) electrophile preliminary, b) Lewis acid, c) substitution product

a) H₂SO₄

b) H₂SO₄

c) SO₃H

How is benzene nitrated: a) electrophile preliminary, b) Lewis acid, c) substitution product

a) NO₃H

b) H₂SO₄

c) NO₂

How is benzene brominated: a) electrophile preliminary, b) Lewis acid, c) substitution product

a) Br₂

b) FeBr₃ / AlCl₃

c) Br

Friedel-Crafts alkylation: a) electrophile preliminary, b) Lewis acid, c) substitution product

a) R₃CCl

b) AlCl₃

c) R₃C

Friedel-Crafts acylation: a) electrophile preliminary, b) Lewis acid, c) substitution product

a) RC=OCl

b) AlCl₃

c) RC=O

a) Are phenols (Ph-OH) more acidic than other alcohols and b) why?

a) yes

b) delocalization: lone pair on O^- conjugate base perpendicular to the plane of the benzene ring, so it can overlap with the π-system. Similar effect to resonance.

inductive effect: sp² carbon is more electronegative and more electron-withdrawing than sp3 carbon due to having higher effective nuclear charge

What are two methods that can be used to prepare benzoic acids (Ph-CO₂H)?

1. oxidation of toluene (Ph-Me) with KMnO₄

2. Grignard with CO₂ (image)

What are the reagents that can be used to prepare aniline (PhNH₂)?

NO₂→NH₂

using Sn/HCl or Pd/H₂

What are the 3 possible regioselective products of electrophilic aromatic substitution?

ortho, meta, para

What does a) activating and b) deactivating group mean?

a) reaction faster than benzene

b) reaction slower than benzene

Ortho, para-directing and activating groups (6)

• alkyl

• NH₂

• NR₂

• NHCOR

• OH

• OR

Why is ortho, para preferred for electron donating groups (with N: or O:)?

intermediate carbocation can be stabilized by/located on the O or N

List the following in order of reactivity: benzene, phenol, aniline, alkyl benzene

aniline>phenol>alkyl benzene>benzene

EXTRA INFO: nitrogen is less electronegative than oxygen, so its lone pair of electrons is even more readily donated to the benzene π system

How can the para addition of Bromine to an aniline be favoured?

meta directing, deactivating groups (7)

• NO₂

• SO₃H

• CO₂H

• CO₂R

• CHO

• COR

• CF₃

Are aromatics with Meta-directing and deactivating (electron withdrawing) groups or ortho,para-directing and activating groups more likely to react?

ortho,para-directing and activating

What are the Ortho,para-directing and deactivating groups

halogens (group 7)

List the types of substituents in decreasing directing order therefore dominant effect (higher= directing effect overwhelms)

ortho,para with N or O>alkyl and halogen>meta directing

What happens to the location of substitution if the directing substituents are in a) same and b) different classes?

a) mixture of all products

b) higher directing power dominates

What molecular feature is required for nucleophilic aromatic substitution?

Electron withdrawing group (note: meta directing) ortho or para to the leaving group

What is the mechanistic difference between nucleophilic and electrophilic aromatic substitution?

electrophilic: double bond electrons are the nucleophile, creates cations

nucleophilic: incoming substituent is the nucleophile, creates anions (centered on ortho/para C to LG)

How does the nature of the leaving group impact the a) rate of reaction of an aromatic nucleophilic substitution and b) why?

a) more electronegative= quicker; F>Cl>Br

b) inductively withdraw electron density from the high energy anionic intermediate

TRUE OR FALSE: Pyridine does not need an EWG to undergo nucleophilic aromatic substitution

TRUE: N acts as the EWG

What is needed for making aromatic compounds undergo an SN1 reaction?

N≡N which is a really really good leaving group

What are two mechanisms for the creation of N≡O⁺?

1. NaNO₂ + H⁺ (acid)

2. BuNO₂ + H⁺ (acid)

What are the reagents and process of creating a diazonium salt?

primary amine (R-NH₂) and N≡O⁺

(aryl; C_nH_2xn+1)N≡N reaction

decomposition to give a planar C⁺

What is the process for creating a phenol (substituents)?

NO₂→NH₂→N≡N^{+ -}X→HO

nitration, reduction, diazotization, hydration

TRUE OR FALSE: Diazo groups can be replaced by other nucleophiles

TRUE: especially halogens associated with K (I) or Cu (Br, Cl)

TRUE OR FALSE: aryl halides cannot be substituted

FALSE: a strong base is needed and it will proceed through a benzyne mechanism

Benzyne mechanism (4)

1. deprotonation ortho- to the leaving group by base

2. carbanion eliminates halogen, creating benzyne

3. base attacks benzyne and reforms carbanion

4. carbanion removed by conjugate acid of base (from first step)

What dictates regioselectivity of a benzyne reaction? (2)

sterics

inductive effect: if electron withdrawing substituent present it stabilizes carbanion formed during addition step

a) How many products can para-Disubstituted halides give in a benzyne reaction and b) why?

a) 2

b) only one benzyne intermediate can be formed and it is too far from the other group for it to exert steric effects

a) What position will the base be added in a benzyne reaction with an electron repelling anion substituent and b) why?

a) meta

b) puts anions furthest from each other

From left to right, name the heterocycles

pyridine, pyrrole, furan, thiophene, indole

Pyridine and DMAP are used as a) what and how and b) which is better and why?

a) nucleophile for carbonyl groups: N knocks out leaving group and makes C more electrophilic

b) DMAP is more nucleophilic due to NMe₂ electron donating group

TRUE OR FALSE: Pyridine is a good substrate for electrophilic and nucleophilic aromatic substitution

FALSE: It sucks at electrophilic but is good at nucleophilic

a) How can unsubstituted pyridines undergo electrophilic substitution and b) what substitution product will be formed?

a) pyridine N-Oxide (see image), which can be reverted to pyridine after by P(OMe)₃

b) para substitution

a) What halogenated pyridine can be made and b) how?

a) chloropyridine

b) pyridine N-oxide and PCl₃

a) How can substituted pyridines undergo electrophilic substitution and b) why?

b) if the substituents are electron donating

b) override pyridine’s unreactivity

a) What are the pyridones’ tautomers and b) which is preferred?

a)

b) keto

How can pyridone be converted into chloropyridines?

POCl₃ reacting with keto (db to O)→ N in ring acts as nucleophile

What is the a) electron rich part of a pyrrole and b) why?

a) the ring

b) delocalization

TRUE OR FALSE: pyrroles are amphoteric

FALSE: moderately acidic

What reagents would you use to synthesize a) pyridine, b) pyrrole, c) thiophene and d) furan from the pictured (or similar) molecule?

a) NH₂OH / HCl, EtOH

b) RNH₂ or NH₃

c) H₂S / HCl

d) H⁺

Electrophilic aromatic substitution of pyrroles is (difficult/easy), but nucleophilic aromatic substitution is (difficult/easy).

Electrophilic aromatic substitution of pyrroles is (difficult/easy), and nucleophilic aromatic substitution is (difficult/easy).

In pyridine, the (ring/N) reacts with electrophiles, in pyrrole, the (ring/N) reacts.

In pyridine, the (ring/N) reacts with electrophiles, in pyrrole, the (ring/N) reacts.

In order of reactivity: furan, pyrrole, thiophene

pyrrole > furan > thiophene

Vilsmeier reaction

1. POCl₃ + RCONMe₂

2. H₂O + RCClN⁺Me₂ + pyrrole

What can be used to imitate the Vilsmeier reaction with (R=Me) in a) thiophene and b) furan?

a) Ac₂O, ZnCl₂, 100^oC

b) Ac₂O, ZnCl₂, 100^oC

Furan + Br₂ in a) aprotic solvent and b) MeOH

a) substitution (4 Br on ring)

b) addition (1 OMe added to each C closest to O)

How can C-C bond formation be promoted in thiophene and furan?

use Bu^--Li⁺ to perform lithiation on C closest to O/S