Chapter 17 - Aromatic Compounds Flashcards
What is the difference between antihistamines that cause drowsiness and those that don’t?
The chapter explores compounds with conjugated π bonds enclosed in a ring, particularly aromatic compounds like benzene and its derivatives.
What are aromatic hydrocarbons also known as?
Arenes
What is the significance of aromatic rings in drugs?
Aromatic rings are particularly common structural features in drugs.
What are the characteristics of aromatic compounds?
Aromatic compounds are stable and significantly less reactive than expected.
What are some examples of top-selling drugs that contain benzene-like aromatic rings?
- Lipitor (atorvastatin)
- Prilosec (omeprazole)
- Zyprexa (olanzapine)
- Norvasc (amlodipine)
- Prevacid (lansoprazole)
- Plavix (clopidogrel)
- Serevent (salmeterol)
- Zoloft (sertraline)
What does the term ‘aromatic’ originally refer to?
It referred to the pleasant odors of compounds derived from fragrant balsams.
What is the primary source of aromatic compounds?
Petroleum, using a process called reforming.
What is the boiling point of benzene?
80°C
What is the boiling point of toluene?
110°C
What is the boiling point of naphthalene?
218°C
How are monosubstituted derivatives of benzene named?
Using benzene as the parent and listing the substituent as a prefix.
What is the common name for 1,2-dimethylbenzene?
ortho-Xylene
What is the common name for 1,3-dimethylbenzene?
meta-Xylene
What is the common name for 1,4-dimethylbenzene?
para-Xylene
What must be used when naming a polysubstituted benzene ring?
Locants to indicate the locations of each substituent.
What is the systematic name for TNT?
2,4,6-Trinitrotoluene
What is the molecular formula of benzene?
C6H6
What bonding theory did August Kekulé propose for benzene?
A ring comprised of alternating double and single bonds.
What is the bond order of each C–C bond in benzene?
1.5
What term is used to describe the phenomenon of resonance in benzene?
It describes the inadequacy of bond-line drawings to represent the true structure.
True or False: Aromatic compounds are reactive and unstable.
False
Fill in the blank: The term ‘aromatic’ is still used to describe all derivatives of benzene, regardless of whether they are _______.
fragrant or odorless
What was the role of Michael Faraday in the study of benzene?
He isolated benzene from the oily residue left by illuminating gas.
What is the bond order of a C-C bond in benzene?
1.5
Why should resonance structures be avoided when proposing reaction mechanisms?
They require scrupulous bookkeeping of electrons.
What is the expected heat of hydrogenation (ΔH) for benzene?
−360 kJ/mol
What is the actual heat of hydrogenation (ΔH) for benzene?
−208 kJ/mol
What is the stabilization energy of benzene?
152 kJ/mol
What does Hückel’s rule state about π electrons in a ring?
A compound can only be aromatic if the number of π electrons is 2, 6, 10, 14, 18, and so on.
What type of molecular orbitals do benzene’s π electrons occupy?
Bonding MOs
True or False: Cyclobutadiene exhibits aromatic stability.
False
How many π electrons does benzene have?
Six π electrons
What is the result of dehydrogenation?
Loss of two hydrogen atoms
What is the implication of a closed-shell electron configuration in benzene?
It provides stabilization energy associated with aromaticity.
What happens to cyclooctatetraene’s stability when it adopts a tub shape?
It avoids unnecessary instability.
What is the molecular formula of compound A in the conceptual checkpoint?
C8H8
What happens to cyclobutadiene when it reacts with itself at low temperatures?
It forms a tricyclic product that rearranges to cyclooctatetraene.
In MO theory, what replaces atomic p orbitals in benzene?
Molecular orbitals
Fill in the blank: The heat of hydrogenation for benzene is _____ kJ/mol.
−208
What type of bonding is present in the molecular orbitals of benzene?
Delocalized bonding
What is the result of having an even number of electron pairs in a ring compound?
The compound does not exhibit aromatic stabilization.
How many bonding MOs are present in cyclobutadiene?
One bonding MO
What is a characteristic feature of antiaromatic compounds?
Open-shell electron configuration
What type of reactions does benzene resist, demonstrating its stability?
Addition reactions
What is the significance of the energy diagram comparing heats of hydrogenation?
It illustrates the relative stability of benzene compared to other compounds.
What is the expected behavior of cyclooctatetraene in terms of stability?
It readily undergoes addition reactions.
What are the types of molecular orbitals (MOs) mentioned?
- Bonding MOs
- Nonbonding MOs
- Antibonding MOs
MOs play a crucial role in determining the stability and properties of molecular structures.
What is the consequence of cyclobutadiene’s open-shell electron configuration?
It is expected to be unstable and antiaromatic.
Cyclobutadiene can avoid this instability by assuming a tub shape.
What is the method for predicting the relative energy levels of molecular orbitals in a ring system?
Frost circle method.
This method involves drawing a circle, inscribing a polygon, and identifying MOs based on their positions.
How many bonding MOs are found in a six-membered ring according to Frost circles?
3 bonding MOs.
This is essential for understanding the aromaticity of six-membered rings.
What is the 4n + 2 rule in relation to aromaticity?
Aromatic compounds must have a number of π electrons that fits the formula 4n + 2.
This rule helps determine whether a compound is aromatic based on its electron count.
What defines a compound as nonaromatic?
Failure to meet the criteria for aromaticity, such as not having a continuous system of p orbitals or not being a ring.
Examples include 1,3,5-hexatriene, which lacks a ring.
What is an annulene?
Compounds consisting of a single ring with a fully conjugated π system.
Examples include [6]annulene (benzene) and [10]annulene.
Why is [10]annulene considered nonaromatic?
It cannot adopt a planar conformation due to steric interactions.
The nonplanarity prevents continuous overlap of p orbitals.
What stabilizes the cyclopentadienyl anion?
It is aromatic and resonance stabilized, fulfilling both criteria for aromaticity.
This anion can accommodate six π electrons.
What is the significance of the pKa values of cyclopentadiene and water?
Cyclopentadiene has a pKa of around 16, similar to water, indicating unusual acidity for a hydrocarbon.
This acidity is attributed to the stability of its aromatic conjugate base.
What two criteria must a compound satisfy to be considered aromatic?
- Must contain a ring of continuously overlapping p orbitals
- Must have a Hückel number of π electrons
These criteria are essential for determining aromaticity.
How does pyridine achieve aromaticity?
It has six π electrons, with the nitrogen’s lone pair occupying an sp2-hybridized orbital, not participating in the aromatic system.
The lone pair’s position allows for the continuous overlap of p orbitals.
How does pyrrole differ from pyridine in terms of aromaticity?
Pyrrole’s lone pair occupies a p orbital, contributing to the aromatic system, giving it a total of six π electrons.
This delocalization explains pyrrole’s lack of basicity.
What happens to the lone pair on nitrogen during protonation in pyrrole?
Protonation destroys the p orbital overlap, thus destroying aromaticity.
This is why pyrrole does not readily function as a base.
What is the role of electrostatic potential maps in comparing pyridine and pyrrole?
They show the localization of the lone pair in pyridine and its delocalization in pyrrole.
Both maps used the same color scale for accurate comparison.
What is a lone pair in the context of aromatic compounds?
A lone pair is a pair of valence electrons that are not shared with another atom and can affect the aromaticity of a compound.
In some cases, lone pairs can participate in the aromatic system, while in others they cannot.
What role does histamine play in physiological responses?
Histamine mediates the onset of allergic reactions and regulates gastric acid secretion.
It is involved in various biological processes in mammals.
In histamine, which lone pair participates in aromaticity?
The lone pair on the nitrogen atom in the ring participates in aromaticity, while the lone pair on the side chain does not.
The nitrogen atom must occupy a p orbital to contribute to the aromatic system.
What is Hückel’s rule?
Hückel’s rule states that a compound is aromatic if it contains a planar ring of p orbitals with (4n + 2) π electrons.
This rule is fundamental for determining the aromaticity of cyclic compounds.
What are polycyclic aromatic hydrocarbons (PAHs)?
PAHs are compounds composed of fused benzene-like rings that exhibit significant aromatic stabilization.
Examples include naphthalene, anthracene, and phenanthrene.
How is stabilization energy measured for polycyclic aromatic hydrocarbons?
Stabilization energy is measured by comparing heats of hydrogenation.
The stabilization energy per ring is generally less than that of benzene.
What is the significance of the structure of antihistamines?
Antihistamines typically have two aromatic rings in close proximity and a tertiary amine to exhibit H1 antagonism.
Structural features are crucial for their effectiveness.
What characteristic feature do nonsedating antihistamines possess?
They contain polar functional groups that prevent them from crossing the blood-brain barrier.
This results in reduced sedative effects compared to first-generation antihistamines.
What occurs at the benzylic position during oxidation?
Oxidation at the benzylic position produces benzoic acid irrespective of the identity of the alkyl group.
This reaction is facilitated by strong oxidizing agents like chromic acid or potassium permanganate.
What type of reaction occurs at benzylic positions via free-radical bromination?
Free-radical bromination occurs selectively at the benzylic position due to resonance stabilization of the intermediate radical.
This allows for the introduction of functional groups at the benzylic position.
What is a benzylic carbocation?
A benzylic carbocation is a carbocation that is resonance stabilized due to its position adjacent to a benzene ring.
This stability allows for rapid SN1 and E1 reactions.
What are the two methods to introduce functionality at a benzylic position?
- Oxidation
- Radical bromination
Oxidation produces benzoic acid, while bromination produces a benzylic halide.
True or False: A benzylic position can undergo elimination reactions.
True
Benzylic halides can undergo both SN1 and E1 reactions due to the stability of the benzylic carbocation.
Fill in the blank: Antihistamines that cause sedation are called _______.
first-generation antihistamines
These antihistamines can cross the blood-brain barrier, leading to sedative effects.
What are the two methods to introduce functionality at a benzylic position?
1) Oxidation 2) Radical bromination
What product is formed from oxidation at the benzylic position?
Benzoic acid
What product is formed from radical bromination at the benzylic position?
Benzylic halide
What are the two possible reactions that a benzylic halide can undergo?
- Substitution (SN1 or SN2) * Elimination (E1 or E2)
What is the first step in synthesizing a compound with a functional group at the benzylic position?
Introduce functionality at the benzylic position
What reagent is used for the radical bromination process?
NBS (N-Bromosuccinimide) and heat
In the synthesis example, what is the second step after radical bromination?
Substitution reaction using NaOH
What reagent is used to oxidize the alcohol to an aldehyde in the synthesis?
PCC (Pyridinium chlorochromate)
What is the product of hydrogenating benzene under forcing conditions?
Cyclohexane
What is the Birch reduction used for?
To reduce benzene to 1,4-cyclohexadiene
What is the key feature of the Birch reduction mechanism?
It involves alternating electron transfer and protonation steps
What is the product of the Birch reduction?
A nonconjugated diene
What effect do alkyl groups have on the stability of the radical anion in Birch reduction?
Alkyl groups are electron donating and destabilize the radical anion
What effect do electron-withdrawing groups have in Birch reduction?
They stabilize the radical anion intermediate
What are the characteristic regions of IR spectroscopy for aromatic compounds?
- 3000–3100 cm−1: C sp2–H stretching * 1450–1650 cm−1: C–C stretching and ring vibrations * 1000–1275 cm−1: C–H bending (in plane) * 690–900 cm−1: C–H bending (out of plane)
What is the typical chemical shift range for protons directly connected to an aromatic ring in 1H NMR spectroscopy?
6.5 to 8 ppm
What is the chemical shift range for benzylic protons in 1H NMR spectroscopy?
2 to 3 ppm
True or False: Protons farther from the aromatic ring exhibit deshielding effects.
False
What are derivatives of benzene called?
Aromatic compounds
Regardless of whether they are fragrant or odorless.
How are monosubstituted derivatives of benzene named?
Using benzene as the parent and listing the substituent as a prefix
IUPAC accepts many common names for monosubstituted benzenes.
What is the term for a benzene ring that is a substituent?
Phenyl group
What descriptors are used to differentiate disubstituted derivatives of benzene?
Ortho, meta, and para
Locants can also be used.
What is the bond order of the C−C bonds in benzene?
1.5
What is required to adequately describe the structure of benzene?
Resonance structures
What unusual stability does benzene exhibit?
It does not react with bromine in an addition reaction.
How can the stabilization energy of benzene be measured?
By comparing heats of hydrogenation
What is Hückel’s rule?
The requirement for an odd number of electron pairs for aromaticity.
What type of compound is cyclobutadiene?
Antiaromatic
What type of compounds are called nonaromatic?
Compounds that fail the first criterion for aromaticity.
What are annulenes?
Compounds consisting of a single ring containing a fully conjugated π system.
What is the lone pair in pyridine’s role in resonance?
Localized and does not participate in resonance.
What happens to benzylic positions during oxidation?
They are oxidized by chromic acid or potassium permanganate.
What reactions can benzylic halides undergo?
SN1, SN2, E1, and E2 reactions.
What is produced in a Birch reduction?
A nonconjugated diene
In which regions of the IR spectrum do aromatic compounds produce signals?
Five distinctive regions
What is the typical 1H NMR signal range for benzylic protons?
Between 2 and 3 ppm
What is the 13C NMR signal range for sp2-hybridized carbon atoms of aromatic rings?
Between 110 and 170 ppm
The integration value of the multiplet near 7 ppm indicates what?
The extent of substitution of the aromatic ring
What does an integration of 5 indicate for an aromatic ring?
A monosubstituted ring
What unique structural feature do C60 fullerenes exhibit?
Composed of fused rings (20 hexagons and 12 pentagons)
What is the common name for C60?
Buckyball
What technique was used to successfully produce graphene?
Using Scotch tape to peel off layers of graphite
What potential applications are being explored for graphene?
Next-generation energy storage devices, electronic touch panels, solar photovoltaic panels, LEDs
What is the primary characteristic of nanotubes?
Stronger and lighter than steel, carry electrical currents efficiently
What are the two main types of reactions at the benzylic position?
Oxidation and substitution reactions
What is the significance of the number of signals in the 13C NMR spectrum for substituted aromatic rings?
Indicates the specific substitution pattern
What is the typical signal range for aromatic protons in 1H NMR?
Around 7 ppm
