Chemistry Y3: Aromatic chemistry Flashcards
What are the properties of benzene?
C6H6
Benzene is planar
Very stable
Pi electrons are delocalised above and below the ring
What is aromatic stacking?
The e rich centre or 1 benzene and e poor edge of another benzene are held together by aromatic stacking
*This happens in DNA
Catatonic Pi stacking
a cation is stacked onto the negative e rich centre of a benzene molecule
What are the 4 valence orbitals of C
2S, 2PX, 2PY, 2PZ
RULES OF AROMATICITY
- Must be cyclic
- Must be planar
- Must be conjugated with p-orbitals at every junction
- 4n+2 Huckel’s rule
what if a compound followed all the rules of aromaticity except Huckels?
It would be anti-aromatic
What is the maximum number of carbons you can have in a ring before it starts to pucker
7 C ring = planar and flat
8 C ring = Puckers
What is the difference between a Nu and an E
E+ = e accepting
Nu-= e donating
Why is benzene losing aromaticity often the RDS
Because benzene is very stable it takes a very good E/Nu to make benzene loser aromaticity
This takes time
What is SeAr
Is is electrophilic aromatic substitution
Which 5 SeAR reactions do we need to know
Halogenation
Nitrations
Sulfonation
Freidel-crafts acylation
Freidel-crafts alkylation
What reagents and conditions are needed for SeAr Bromination?
Ar-H—-> Ar-X
AlBr3/AlCl3 (LA)
Br2/Cl2
Heat
What reagents and conditions are needed for SeAr Nitration?
Ar-H —–> Ar-NO₂
E⁺= NO₂⁺
HNO3
H2SO4
HEAT
What reagents and conditions are needed for SeAr Sulfonation?
Ar-H —> Ar-SO₃H⁺
E⁺= SO₃H⁺
conc. H2SO4 + HEAT
What reagents and conditions are needed for SeAr Freidel-Crafts Alkylation?
Ar-H —–> Ar-C(R ₃)
E⁺= R₃C⁺
R₃C-X
LA
HEAT
What reagents and conditions are needed for SeAr Freidel-Crafts Acylation?
Ar-H —-> Ar-c(=O)R
E⁺= (RCO)⁺
RC(=O)Cl
LA
HEAT
In terms of product formed which is better acylation or alkylation?
ACYLATION
What does substituting an arene do to its reactivity
*Changes its reactivity
*determines location of the next attack
What happens if an EDG is attached to benzene
*Electrons are pushed into the ring
*Increases RoR
*Ring has more density
*O/P directing
What happens if an EWG is attached to benzene?
Pulls e density out of ring
*Decreases RoR
*Ring has less e density
*Meta
what is the best activator
NR2
What is the best Deactivator
NO2
Does activated or deactivate benzene stabilise the intermediate?
Activated benzene
Which has the higher activation energy EWG or EDG?
EWG - DEACTIVATES at O/P- therefore is meta directing. Slows reaction
What is the induction mechanism?
substituents donate/withdraw e density inductively via a sigma bond
What is the resonance mechanism?
Substituents donate/withdraw e density via the Pi network
*in resonance mechanisms you should be able to push e with curly arrows (resonance structures)
What are halogens
They’re EWG but direct to O/P not Meta
Are halogens resonance or induction?
They’re both
*They deactivate the ring due to inductive withdrawal
*LP resonance increases e density in O/P
*so, O/P directing for SeAR
Which has more effect resonance or induction?
RESONANCE
What happens if a positive charge in a cation ends up next to a substituent?
The substituent could stabilise or destabilise the cation (+ve) charge depending on what it is
Give 2 examples of EDGs that use induction
CH3 and C6H5
Give 2 examples of EWGs that use induction? And explain what happens when these react
NR3 and CF3- Nothing happens
Is Phenol activating of deactivating
V activating
acts as acid
O/P
can push e into ring
What does phenoxide look like? is it activating or deactivating
Benzene ring with O- attached
vvv activating
What does aniline look like ? is it activating or deactivating
Benzene with NH2 attached
LP on N
VV activating
what happens when you put aniline in acidic conditions?
It forms anilinium cation = extremely deactivating - reaction wont happen
what happens to Phenol in basic conditions?
it is converted to phenoxide
*This is more reactive than phenol
What is the benefit of reacting with phenol instead of benzene
It is more reactive. Reactions occur more easily
Less extreme conditions are needed
What happens when you brominate a phenol?
Tribromination
How do we achieve mono-nitrate a phenol?
Use dilute HNO3 to give a low conc
What reagents do you need for a FC reaction with Phenoxide?
A weak catalyst e.g HF
or even non-catalytic electrophiles e.g. CO2
How can we achieve SeAR reactions with a phenol?
We can temporarily protect it by converting it to an ester via ACYLATION
*With Acid chlorides and acid anhydrides
*Esters can still push e density into the ring
*O/P directing still
BUT
*Some e density is puller towards the ester (=O) less e density made available that in phenol
*Some e density is stabilised through ester double bond
If there is a big group attached to a benzene which position is a 2nd group likely to attach at?
PARA - more space
less steric hinderance
When doing all SeAR reactions with aniline what do we need to consider?
They all take place in acidic solution so,
-Need so work round this e.g Basic conditions
-Or anilinium cation is made
How do we moderate aniline reactivity (EAS)? And what does the reaction look like?
can temorarily protect aniline as an amide via acylation
*activating effect is reduced due to competing withdrawal of a N LP by the carbonyl group of the amide
The reaction:
*must be in basic conditions
*SeAR will go to PARA 1st
*Gives Mono-substitution mainly in PARA (OCCASIONALLY ORTHO)
why is reacting with an amide preferable to reacting with aniline
- Moderates reactivity
- can use acidic conditions
3.product will be mono-substituted - Aniline acylation is reversible (Just add a base)
How do we make aniline
Benzene —(Nitraiton)—> Nitrobenzene —-(reduction)—-> Aniline
What conditions are needed to go from Aniline to Anilinium cation (and vice versa)?
- H+
- OH-
or can form with a LA attached in which case
1. LA
what conditions are needed to go from aniline to nitrobenzene (and vice versa)?
- Sn/HCl then neutralise
- Pd/C , H2 reduction
what conditions are needed to go from aniline to amide (and vice versa)?
- NaOAc (Basic conditions)
- H3O+
what conditions are needed to go from aniline to Diazonium salt
- NaNO2 and HCl
How do aromatics react with nucleophiles
*e density is pushed into the ring from Nu
*aromaticity is lost =RDS
*Both LG and NU are attached
*SP3 hybridised - resonance possible
*LG eliminated
*aromaticity regained
Why is a good EWG needed for SnAR
*to pull some of the e density out of the ring
*to stabilise the anion
*EWG should be O/P to LG
what 3 things do we need for SnAR
*EWG O/P to LG/Nu
*Good leaving group F- or Cl-
*Nu
Stabilisation can either be …?
resonance or inductive
-This stabilises the ring’s -ve charge
Inductive stabilisation?
Pushes e density out via sigma bonds
What position should the EWG be in in SnAR
ORTHO/PARA
Resonance stabilisation
Pushes e density out via Pi system e.g NO2
What are common Nucleophiles?
O, N or CN
what are good EWGs and what do they do?
NO2, Sulfur based groups (SO3R), CN, and carbonyl groups
*They activate the SnAR reaction
*They stabilise the anion intermediate
Why is resonance substitution better than induction?
*Single resonance substitution
*Faster and easier
If there are 2 EWGs that are resonance what does this mean compared with 1?
that even less extreme conditions are needed and reaction goes faster.
Can resonance substitution for SnAR occur in the META position?
No not even in extreme conditions
Why are Halides good leaving groups?
*the halide creates a dipole with the carbon
*The -ve Nu can attack the partially +ve carbon
*e density can be pushed down to be stabilised by EWG
* the e density can be pushed back up to lose the F- ion (fast step)
Which is the best Nu:
Amines
Alcohols
Alkoxides
Alkoxides>Amines>Alcohols
Why are diazonium salts useful?
*Have N(triple bond)N
*Good starting point
*N2 is a v good LG, readily eliminated a N2 (g)
*Leaves benzene as carbocation (V hard to do)
*So DS is a source of aromatic carbocations
Why are aryl carbocations so unstable
Breaks SP2 hybridisation by sharing e with N
*Ring can no longer be stabilised by resonance
*can be used as an E+
How do you form a DS from benzene?
- Nitration -> nitrobenzene with HNO3 and H2SO4
- Reduction -> Aniline with H2 and Pd/C
- -> DS with HCl and NaNO2, <5℃
How do you get from a DS to a phenol?
- -> Aryl cation with H2SO4, H2O and HEAT (N2 given off)
- Add H2O -> intermediate
- -> phenol with HSO4-
How to make an Aryl iodide from DS?
- <25℃ -> aryl cation
- KI (I- attacks), <25℃
- -> Aryl iodide
Why is the Sandmeyer reaction useful?
Helps to introduce weaker Nu
*Its a radical mechanism
what does the Sandmeyer reaction use?
Cu catalysis: Cu-X and H-X
X can be:
Cl, Br, CN
What is the Balz-scheimann reaction used for?
*To make aromatic fluorines
How do you make an aromatic fluorine from a DS?
- DS —(NaBF4 and NaCl)–>
- Intermediate
- gentle heating, N2 removed
- Fluorobenzene + BF3 made
How do we create tribrominated benzene from nitrobenzene?
- Nitrobenzene -> analine with H2 and Pd/C
- Aniline gets tribrominated using Br2
- -> DS using HCl, NaNO2, <5℃
- -> tribrominated benzene with H3PO2, H2O, HEAT (N2 removed)
Reagents for DS -> Benzene
H2PO2, H2O, HEAT
(N2 removed)
How can DS act as electrophiles in SeAR
- Introduce DS as E+ to benzene
- Benzene must have an EDG
- Forms bonds in O/P
- C-N bond at O/P
What are heterocycles?
atoms other than c are incorperated into rings
e.g. N, S or O
If a LP is in the SP2 orbital is it counted in Huckel’s?
No as its not in a P-orbital
-Can’t contribute to the ring
What is Huckels rule?
4n+2
In 5 membered rings and heteroaromatics what does a -ve charge mean
an extra e
What is Pyrrole?
Neural, Stable and aromatic
non-basic
forms 5-memebered heteroaromatic
has 2 LPs that contributes to Pi system
why are Pyrrole and pyridines LPs treat differently?
Pyrrole- Has LP that are in P orbital - so they contribute to Pi system
Pyridine- Has LP that sity in SP2 orbital, can’t contribute to ring
-Making it basic
If an anion has resonance, what does this mean?
The LP must be in the P orbital as its contributing to the ring
How can we make an aromatic from cyclopentadiene (non-aromatic)
- remove 1H
- gives a cyclopentadienyl anion = aromatic
Imidazole has 2 N in a 5 membered ring, which orbitals are their LPs in
1st N (LP must be in P orbital, SP2 orbital all full)
2nd N (LP must be in SP2 orbitals
is imidazole aromatic?
6 Pi e, neutral, planar, cyclical
=YES
Once you have a nitro group in O/P where will the next Nitro group direct?
Meta- NO2 is M directing
Once you have a CH3 group where will the next group attack?
O/P
If we have an EWG attached where will the next group attach?
Meta
what has the bigger effect activating or deactivating?
activating
If you want to keep Nitrating what do you do?
NO2 is Meta directing- not favourable but have to keep increasing temperature
How are halogens inductive and resonance?
- Inductive withdrawal through sigma bond-
- resonance can push LP into ring increasing e dinsity at o/p- sabilising cation
how does halogenic inductive withdrawal have different effects in SeAR and SnAR
SeAR= inductive withdrawal destabilising cation
SnAR = inductive withdrawal stabilising anion
how do you get from alkylbenzenes to benzoic acid?
oxidation using hot KMNO4
Acyl to acyl chloride?
- Acylbenzene -> Alkyl uising Zn(Hg) nad Hcl
- Alkylbenzene to Benzoic acid using hot KMNO4
- Benzoic acid -> Acyl chloride using SOCl2
What is retrosynthesis?
That the order of the reaction can change the outcome of the product
-Relation to M or O/P directing
Benzene to 1-fluoro-3-bromobenzene
- Nitration (HNO3 and H2SO4)
- Bromination at Meta (Br2 and AlBr3)
- Reduction - Aniline (H2 and Pd/C)
- diazotisation/ fluorination (NaNO2 and HCl) followed by (NaBF4 and HEAT)
