Organic Chemistry

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Organic Chemistry
William H. Brown Christopher S. Foote
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• Aromatics I
• Chapter 20

3
Benzene - Kekulé

• The first structure for benzene was proposed by
  August Kekulé in 1872
• This structure, however, did not account for the
  unusual chemical reactivity of benzene

4
Benzene - MO Model

• The concepts of hybridization of atomic orbitals
  and the theory of resonance, developed in the
  1930s, provided the first adequate description of
  benzenes structure
• the carbon skeleton is a regular hexagon, with
  all C-C-C and H-C-C bond angles 120

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Benzene - MO Model
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Benzene - MO Model

• Combination of six 2p atomic orbitals gives six
  molecular orbitals
• three bonding MOs and
• three antibonding MOs
• In the ground state, the six pi electrons of
  benzene occupy the three bonding MOs

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Benzene MO Model

• the stability of benzene results from the fact
  that these three bonding MOs are much lower in
  energy than the six uncombined 2p atomic orbitals

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Benzene - Resonance

• We often represent benzene as a hybrid of two
  equivalent Kekulé structures
• each makes an equal contribution to the hybrid
  and thus the C-C bonds are neither double nor
  single, but something in between

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Benzene - Resonance

• Resonance energy the difference in energy
  between a resonance hybrid and the most stable of
  its hypothetical contributing structures in which
  electrons are localized on particular atoms and
  in particular bonds
• One way to estimate the resonance energy of
  benzene is to compare the heats of hydrogenation
  of benzene and cyclohexene

10
Benzene
11
Concept of Aromaticity

• The underlying criteria for aromaticity were
  recognized in the early 1930s by Erich Hückel,
  based on MO calculations
• To be aromatic, a compound must
• be cyclic
• have one p orbital on each atom of the ring
• be planar or nearly planar so that there is
  continuous or nearly continuous overlap of all p
  orbitals of the ring
• have a closed loop of (4n 2) pi electrons in
  the cyclic arrangement of p orbitals

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Frost Circles

• Inscribe a polygon of the same number of sides as
  the ring to be examined such that one of the
  vertices is at the bottom of the ring
• The relative energies of the MOs in the ring are
  given by where the vertices touch the circle
• Those MOs
• below the horizontal line through the center of
  the ring are bonding MOs
• on the horizontal line are nonbonding MOs
• above the horizontal line are antibonding MOs

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Frost Circles

• Following are Frost circles describing the MOs
  for monocyclic, planar, fully conjugated four-,
  five-, and six-membered rings

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Aromatic Hydrocarbons

• Annulene a cyclic hydrocarbon with a continuous
  alternation of single and double bonds
• 10Annulene according to Hückels criteria,
  this unsaturated hydrocarbon should be aromatic
• it is cyclic
• it has one 2p orbital on each carbon of the ring,
• it has 4(2) 2 10 pi electrons
• It is not aromatic, however, because it is not
  planar

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10Annulene

• nonbonded interactions between the two hydrogens
  that point inward toward the center of the ring
  force the ring into a nonplanar conformation in
  which overlap of the ten 2p orbitals is no longer
  continuous

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14Annulene

• this unsaturated hydrocarbon meets the Hückel
  criteria and is aromatic

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18Annulene

• This unsaturated hydrocarbon is also aromatic

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Antiaromatic Hydrocbn

• Antiaromatic hydrocarbon a monocyclic, planar,
  fully conjugated hydrocarbon with 4n pi electrons
  (4, 8, 12, 16, 20...)
• an antiaromatic hydrocarbon is especially
  unstable relative to an open-chain fully
  conjugated hydrocarbon of the same number of
  carbon atoms
• Cyclobutadiene is antiaromatic. In the
  ground-state electron configuration of this
  molecule,
• two electrons fill the ?1 bonding MO
• the remaining two electrons lie in the ?2 and ?3
  nonbonding MOs

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Cyclobutadiene

• planar cyclobutadiene has two unpaired electrons,
  which make it highly unstable and reactive

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Cyclobutadiene

• cyclobutadiene is trapped within the cage of a
  larger molecule called a hemicarcerand (to rotate
  this molecule, see the accompanying CD)

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Cyclooctatetraene

• Planar cyclooctatetraene, if it existed, would be
  antiaromatic it would have two unpaired
  electrons in ?4 and ?5 nonbonding MOs

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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 are other than carbon
• Pyridine and pyrimidine are heterocyclic analogs
  of benzene each is aromatic.

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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
• pyridine has a resonance energy of 134 kJ (32
  kcal)/mol, slightly less than that of benzene

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Furan

• 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 Hydrcbn 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

29
Cyclopentadienyl C

• if planar cyclopentadienyl cation existed, 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

• 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

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Cyclopentadienyl Anion

• 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 C

• 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 the 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 Derivs

• 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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NMR Spectroscopy

• Hydrogens bonded to a benzene ring appear in the
  region ? 6.5 to 8.5
• Aryl hydrogens absorb further downfield than
  vinylic hydrogens, which is accounted for by an
  induced ring current
• the induced ring current has an associated
  magnetic field which opposes the applied field in
  the middle of the ring but reinforces it on the
  outside of the ring
• thus, hydrogens on the benzene ring come into
  resonance at a lower applied field that is, at a
  larger chemical shift than vinylic hydrogens

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NMR Spectroscopy

• There are, of course, no hydrogens on the inside
  of a benzene ring. But there are in larger
  annulenes, for example 18annulene

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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, compounds that also contain the -OH
  group

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Acidity of Phenols

• 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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Acidity of Phenols

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

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Acidities of Phenols

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

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Acidities 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

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Alkyl-Aryl Ethers

• Alkyl-aryl ethers can be prepared by the
  Williamson ether synthesis
• but only using phenoxide salts and alkyl halides
• aryl halides are unreactive to SN2 reactions
• The following two examples illustrate
• the use of a phase-transfer catalyst
• the use of dimethyl sulfate as a methylating agent

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Alkyl-Aryl Ethers
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Kolbe Carboxylation

• Phenoxide ions react with carbon dioxide to give
  a carboxylic salt

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Kolbe Carboxylation

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

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Oxidation to 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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Oxidation of Phenols
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Quinones

• Perhaps the most important chemical property of
  quinones is that they are readily reduced to
  hydroquinones

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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) is by a radical
  mechanism

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Benzylic Reactions

• Benzylic radicals (and cations too) 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

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Benzylic Halogenation

• Benzylic chlorination is also regioselective, but
  less so than benzylic bromination
• The order of regioselectivity is
• which parallels BDEs for the formation of radicals

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Hydrogenolysis

• Hydrogenolysis cleavage of a single bond by H2
• among ethers, benzylic ethers are unique in that
  they are cleaved under conditions of catalytic
  hydrogenation

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Benzyl Ethers

• The particular value of benzyl ethers is that
  they can serve 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

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Benzyl Ethers

• protect the phenolic -OH, carry out the
  hydroboration/oxidation, and then remove the
  benzyl protecting group by hydrogenolysis

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Prob 20.15

• State the number of p orbital electrons in each.

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Prob 20.23

• From this spectral data, write a structural
  formula for compound F, C12H16O.

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Prob 20.24

• From this spectral data, write a structural
  formula for compound G, C10H10O.

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Prob 20.29

• Compound K, C10H12O2, is insoluble in water, 10
  NaOH and 10 HCl. Given this information and the
  following spectral data, propose a structural
  formula for compound K.

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Prob 20.30

• Propose a structural formula for each compound.

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Prob 20.31

• Each compound shows strong, sharp absorption
  between 1700 and 1720 cm-1, and strong, broad
  absorption over the region 2500-3500 cm-1.

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Prob 20.35

• Arrange the entries in each set in order of
  increasing acidity.

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Prob 20.36

• Explain the trends in acidity of phenol and the
  monofluoro derivatives of phenol.

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Prob 20.38

• From each pair, select the stronger base.

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Prob 20.39

• Describe a chemical procedure to separate a
  mixture of these compounds and recover each in
  pure form.

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Prob 20.46

• Account for the following order of reactivity
  under SN1 conditions.

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Prob 20.47

• Propose a mechanism for this rearrangement.
  Account for the fact that the product is
  2-phenylpropanal rather than its constitutional
  isomer, 1-phenyl-1-propanone.

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Prob 20.49

• Synthesize these compounds from ethylbenzene.

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Prob 20.50

• Show how to convert 1-phenylpropane to the
  following compounds.

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Prob 20.51

• Given this retrosynthetic analysis, propose a
  synthesis for cabinoxamide. Note that aryl
  bromides form Grignard reagents much more readily
  than aryl chlorides.

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Prob 20.52

• Propose (1) a mechanism for formation of I, (2)
  a structure for II and a mechanism for its
  formation, and (3) a mechanism for the formation
  of cromolyn sodium.

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Prob 20.53

• Describe the chemistry of each step.

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Prob 20.53 (contd)

• describe the chemistry of each step

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• Aromatics I

End of Chapter 20