Properties of Heteroaromatics Flashcards
Pyridine is isoelectric with benzene
What does this mean?
They both have 6 electrons in six parallel p-orbitals that make up the 6π electrons for aromaticity
How many electron in the Nitrogen p-orbtial contribute to the π-system
one electron
Can the Nitrogen LP in pyridine delocalise?
The nitrogen LP in the sp² orbital is orthogonal to ring
Hence is not involved in delocalisation
How does the Nitrogen affect the reactivity and properties compared to benzene
Nitrogen atom lowers the HOMO and LUMO orbital energies relative to benzene
What is the resonance stabilisation in benzene like relative to pyridine
Resonance stabilisation (aromatic stabilisation energy) is slightly lower in pyridine
Hence is it easier to break the aromatic ring in pyridine
What are the bond lengths like in pyridine compared to benzene
They are generally shorter in pyridine (especially the C-N bond)
Due to increased electronegativity of nitrogen relative to carbon
What is the electron density like in the atoms in pyridine vs benzene
electron denisty is the same across all carbons in benzene
Due to nitrogen being more electronegative than carbon, there is increased electron density at nitrogen and a slight decrease in electron density at the other 5 carbons
In 1H NMR all the hydrogens are chemically equivalent for benzene so only 1 peak is produced at 7.2ppm
What is the 1H NMR like for pyridine
There is a line of symmetry through the nitrogen and para-carbon meaning there is only 3 hydrogen environment
The H₂ peak is further downfield due to the inductively withdrawing effects of nitrogen
H₃ and H₄ peaks appear around the same values for the benzene chemical shifts (7.2ppm)
There is coupling between H₂ and H₃ protons as well as H₃ and H₄ protons
In ¹³C NMR all the carbons are chemically eqivalent for benzene so only 1 peak is produced at 128.5ppm
What is the ¹³C NMR like for pyridine
There is a line of symmetry through the nitrogen and the para-carbon meaning there is only 3 carbon environments
The C₂ peak appears further downfield due to the inductively withdrawing effect of nitrogen
Due to there being mutiple resonance forms of pyridine, positive charge can exist on C₂ and C₄ which will desheid them so they will appear downfield of 128.5ppm
When naming any substituents on pyridine, which atom has priority 1
the heteroatom has priority 1
So in this case nitrogen
If the lone pair in pyridine is not delocalised around the atomic ring, how does this affect reactivity
The lone pair is available for reactions
Pyridine is a weak base (availability of LP)
And a reasonable nucleophile (attack electron deficient atoms)
Nucleophilic aromatic substitution for pyridine is easy
How does pyridine act as a nucleophile?
Using the lone pair on the nitrogen
What is the basicity of pyridine vs piperidine
- Pyridine is a weaker base than piperidine (amine)
- This is because the LP in pyridine is in a sp² orbital and is less avaiable as it is held closer to the nucleus
- The LP in piperidine is sp³ hybridised
How can substituents affect the basicty of pyridine
- Electron-withdrawing groups decrease basiticty
- Electron-donating groups increase basicity
The electron-withdrawing group makes nitrogen even more positively charged, so it is less likely to loose the hydrogen
How do extra nitrogen atoms in the ring effect basicity
Extra nitrogen atoms in the ring exert an electron-withdrawing effect, decreasing basicity
The additional nitrogen will pull away electron and destabilise the positive charge, more likely to loose the nitrogen
What is special about 3-hydroxypyridine
Hydroxypyridine is both a weak acid and base
* Acid: Nitrogen is an electron-withdrawing group and will increase acidity of OH
* Base: OH will stabilise positive charge due to it being electron-donating
In both cases it is more acidic than phenol and more basic than pyrimidine
Why is 3-hydroxypyridine more acidic and basic than 2-hydroxy and 4-hydroxypyridine
2-hydroxy- and 4-hydroxypyridine exist as two tautomeric forms
In the 2 and 4 forms the electron are delocalised within the C=O bond (3-hydroxyl cannot delocalise)
How can pyridine act as a nucleophilc catalyst (due to alcohol being a weak nucleophile)
e.g. in ester fomation from acyl chloride and alcohol
- Pyridine attacks using its Lone pair at an electron deficient site (e.g. C=O carbon) causing chlorine to leave
- Then nucleophilic attack of an alcohol (at C=O carbon) results in pyridine leaving (resulting in an ester forming)
which is the strongest base?
A
Carbon is less electronegative than oxygen and nitrogen, so lone pair more available
AND the negative charge cannot be stabilised by resonance effects like in D
In Pyrrole, what orbital is the nitrogen LP in
The nitrogen is sp² hybridised
The nitrogen lone pair is in the 2p orbital parallel to the carbon 2p orbital
How many electrons does pyrrole contribute to the π system
Contributes two electrons to the π-system
Can the nitrogen LP in pyrrole delocalise?
The lone pair is delocalised around the aromatic ring
Hence it is unavailable for reactivity, making pyrrole non-basic and non-nucleophilic
Pyrrole and other 5-membered heterocycles are electron-rich
Meaning what type of mechanism is easy
Electrophilic aromatic substitution is very easy
What is the resonance stabilisation like in pyrrole vs thiophene and furan
thiophene>pyrrole>furan
due to oxygen and nitrogen being more electronegative resulting in poor orbital overlap and electron delocalisation = decreased resonance stability
whereas sulphur has an electronegativity comparable to carbon so there is good orbital overlap and LP is fully delocalised in the π system = strong resonance stabilisation
What is special about imidazole
imidazole has:
* one (non-basic + non-nucleophilic) pyrrole-like nitrogen, with the LP delocalised within the aromatic system
* one (basic, nucleophilic) pyridine-like nitrogen, the LP orthogonal to aromatic π-system
In a very strong acid, pyrrole can be protonated
What is the catch?
It protonates on carbon, not on nitrogen
(pKaH = -3.8)
Where does imidazole protonate?
How does it’s basicity compare to pyridine and piperidine?
- Imidazole will protonate at the ‘pyridine-like’ nitrogen (you can delocalised the charge across the 2 nitrogens, hence more acidic)
- It is more basic than pyridine but less basic than piperidine
How acidic is pyrrole compared to other amides and why?
An effect of the delocalisation of the Nitrogen LP is to make pyrrole weakly acidic comparable to an amide
What is an azole?
Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring
How can you increase the acidicity of azoles?
The acidicty increases as the number of ring nitrogens increases
