Heterocyclic Aromatics

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Heterocyclic Aromatics

• Heterocyclic compound A compound that contains
  more than one kind of atom in a ring.
• In organic chemistry, the term refers to a ring
  with one or more atoms that differ from carbon.
• Pyridine and pyrimidine are heterocyclic analogs
  of benzene each is aromatic.

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Database for unknown compounds
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Pyridine

• The nitrogen atom of pyridine is sp2 hybridized.
• The unshared pair of electrons lies in an sp2
  hybrid orbital and is not a part of the six pi
  electrons of the aromatic system (the aromatic
  sextet).
• Resonance energy of pyridine is134 kJ (32
  kcal)/mol.

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Furan and Pyrrole

• The oxygen atom of furan is sp2 hybridized.
• one unshared pairs of electrons on oxygen lies in
  an unhybridized 2p orbital and is a part of the
  aromatic sextet.
• The other unshared pair lies in an sp2 hybrid
  orbital and is not a part of the aromatic system.
• The resonance energy of furan is 67 kJ (16
  kcal)/mol.

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Other Heterocyclics
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Aromatic Hydrocarbon Ions

• Any neutral, monocyclic, unsaturated hydrocarbon
  with an odd number of carbons must have at least
  one CH2 group and, therefore, cannot be aromatic.
• Cyclopropene, for example, has the correct number
  of pi electrons to be aromatic, 4(0) 2 2, but
  does not have a closed loop of 2p orbitals.

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Cyclopropenyl Cation

• If, however, the CH2 group of cyclopropene is
  transformed into a CH group in which carbon is
  sp2 hybridized and has a vacant 2p orbital, the
  overlap of orbitals is continuous and the cation
  is aromatic.

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Cyclopropenyl Cation

• When 3-chlorocyclopropene is treated with SbCl5,
  it forms a stable salt.
• This chemical behavior is to be contrasted with
  that of 5-chloro-1,3-cyclopentadiene, which
  cannot be made to form a stable salt.

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Cyclopentadienyl Cation

• If planar cyclopentadienyl cation were to exist,
  it would have 4 pi electrons and be antiaromatic.
• Note that we can draw five equivalent
  contributing structures for the cyclopentadienyl
  cation. Yet this cation is not aromatic because
  it has only 4 pi electrons.

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Cyclopentadienyl Anion, C5H5-

• To convert cyclopentadiene to an aromatic ion, it
  is necessary to convert the CH2 group to a CH
  group in which carbon becomes sp2 hybridized and
  has 2 electrons in its unhybridized 2p orbital.

n 1
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Cyclopentadienyl Anion, C5H5-

• As seen in the Frost circle, the six pi electrons
  of cyclopentadienyl anion occupy the p1, p2, and
  p3 molecular orbitals, all of which are bonding.

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Cyclopentadienyl Anion, C5H5-

• The pKa of cyclopentadiene is 16.
• In aqueous NaOH, it is in equilibrium with its
  sodium salt.
• It is converted completely to its anion by very
  strong bases such as NaNH2 , NaH, and LDA.

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Cycloheptatrienyl Cation, C7H7

• Cycloheptatriene forms an aromatic cation by
  conversion of its CH2 group to a CH group with
  its sp2 carbon having a vacant 2p orbital.

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Nomenclature

• Monosubstituted alkylbenzenes are named as
  derivatives of benzene.
• Many common names are retained.

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Nomenclature

• Benzyl and phenyl groups

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Disubstituted Benzenes

• Locate two groups by numbers or by the locators
  ortho (1,2-), meta (1,3-), and para (1,4-).
• Where one group imparts a special name, name the
  compound as a derivative of that molecule.

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Disubstituted Benzenes

• Where neither group imparts a special name,
  locate the groups and list them in alphabetical
  order.

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Polysubstituted Derivatives

• If one group imparts a special name, name the
  molecule as a derivative of that compound.
• If no group imparts a special name, list them in
  alphabetical order, giving them the lowest set of
  numbers.

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Phenols

• The functional group of a phenol is an -OH group
  bonded to a benzene ring.

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Phenols

• Hexylresorcinol is a mild antiseptic and
  disinfectant.
• Eugenol is used as a dental antiseptic and
  analgesic.
• Urushiol is the main component of the oil of
  poison ivy.

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Acidity of Phenols

• Phenols are significantly more acidic than
  alcohols.

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Acidity of Phenols

• Separation of water-insoluble phenols from
  water-insoluble alcohols.

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Acidity of Phenols (Resonance)

• The greater acidity of phenols compared with
  alcohols is due to the greater stability of the
  phenoxide ion relative to an alkoxide ion.

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Phenol Subsitituents (Inductive Effect)

• Alkyl and halogen substituents effect acidities
  by inductive effects
• Alkyl groups are electron-releasing.
• Halogens are electron-withdrawing.

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Phenol Subsitituents(Resonance, Inductiion)

• Nitro groups increase the acidity of phenols by
  both an electron-withdrawing inductive effect and
  a resonance effect.

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Acidity of Phenols

• Part of the acid-strengthening effect of -NO2 is
  due to its electron-withdrawing inductive effect.
• In addition, -NO2 substituents in the ortho and
  para positions help to delocalize the negative
  charge.

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Acidity of Phenols

• Phenols are weak acids and react with strong
  bases to form water-soluble salts.
• Water-insoluble phenols dissolve in NaOH(aq).

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Acidity of Phenols

• Most phenols do not react with weak bases such as
  NaHCO3 they do not dissolve in aqueous NaHCO3.
• Carbonic acid is a stronger acid than phenol.
  Therefore, the position of this equilibrium lies
  far to the left.

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Synthesis Alkyl-Aryl Ethers

• Alkyl-aryl ethers can be prepared by the
  Williamson ether synthesis
• but only using phenoxide salts and haloalkanes.
• haloarenes cannot be used because they are
  unreactive to SN2 reactions.

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Synthesis Alkyl-Aryl Ethers
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Synthesis Kolbe Carboxylation

• Phenoxide ions react with carbon dioxide to give
  a carboxylate salt.

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Mechanism Kolbe Carboxylation

• The mechanism begins by nucleophilic addition of
  the phenoxide ion to a carbonyl group of CO2.

Go back to aromatic structure
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Synthesis Quinones

• Because of the presence of the electron-donating
  -OH group, phenols are susceptible to oxidation
  by a variety of strong oxidizing agents.

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Quinones
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Quinones

• Readily reduced to hydroquinones.

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Coenzyme Q

• Coenzyme Q is a carrier of electrons in the
  respiratory chain.

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Vitamin K

• Both natural and synthetic vitamin K (menadione)
  are 1,4-naphthoquinones.

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Benzylic Oxidation

• Benzene is unaffected by strong oxidizing agents
  such as H2CrO4 and KMnO4
• Halogen and nitro substituents are also
  unaffected by these reagents.
• An alkyl group with at least one hydrogen on its
  benzylic carbon is oxidized to a carboxyl group.

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Benzylic Oxidation

• If there is more than one alkyl group on the
  benzene ring, each is oxidized to a -COOH group.

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Benzylic Chlorination

• Chlorination and bromination occur by a radical
  chain mechanism.

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Mechanism Benzylic Reactions

• Benzylic radicals (and cations also) are easily
  formed because of the resonance stabilization of
  these intermediates.
• The benzyl radical is a hybrid of five
  contributing structures.

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Benzylic Halogenation

• Benzylic bromination is highly regioselective.
• Benzylic chlorination is less regioselective.

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Hydrogenolysis

• Hydrogenolysis Cleavage of a single bond by H2
• Benzylic ethers are unique in that they are
  cleaved under conditions of catalytic
  hydrogenation.

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Synthesis, Protecting Group Benzyl Ethers

• The value of benzyl ethers is as protecting
  groups for the OH groups of alcohols and phenols.
• To carry out hydroboration/oxidation of this
  alkene, the phenolic -OH must first be protected
  it is acidic enough to react with BH3 and destroy
  the reagent.