Circular molecules: rings

1
Circular molecules rings

• Prof. Fraser-Stoddart (UCLA, USA) has (amongst
  others) found methods to form very peculiar
  cyclic intertwining molecules the so-called
  catenanes

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Cubane

• Cubane, a perfectly cubical molecule

3
Propellanes
4
Angle strain

• The ideal tetrahedral angle of 109 degrees cannot
  be reached

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Cyclopropane

• In cyclopropane, the angle strain is relatively
  high maximum overlap between the sp3-orbitals is
  not possible, therefore the CC-bonds are weaker
  than regular CC-bonds

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In other words..
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The real values

• The bond dissociation energy can be measured and
  indicates a difference of 25 kcal/mol

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Cyclobutane

• The bending of the four-membered ring causes a
  relief of torsional strain

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Conformations of cyclobutane

• The top in the energy curve corresponds with
  the planar four-membered ring conformation

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Cyclopentane

• The saturated cyclopentane skeleton exists either
  in the envelope or in the twist conformation
  this causes an increase of angle strain, but a
  release of torsional strain

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Next cyclohexane
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The chair conformation

• The most stable conformation of cyclohexane is
  the so-called chair conformation
• Make sure that you know how to draw the chair
  form !

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Axial vs equatorial

• Cyclohexane contains 6 axial and 6 equatorial
  substituents 3 of each are up and 3 of each
  are down

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The ring flip

• What happens with the hydrogen atoms if you
  convert one chair into another chair by
  flipping the ring ?

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Cyclohexane (contd)

• Cyclohexane can exist in a variety of
  conformations
• The half chair is the predominant conformation in
  case a double bond is present

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Energy profile of cyclohexane

• Beside the two chair conformations, the boat
  conformation is important it is, however,
  energetically much less favored

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Question

• Rationalize the difference in stability between
  the chair and the boat conformation

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Answers

• There is a strong repulsion between the hydrogens
  on the top
• There is a significant torsional strain because
  of the eclipsing hydrogens

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Substituent effects

• Substituents prefer to be in an equatorial
  position !

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Rationale
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The larger the R-substituent
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.the more equatorial
Compound Methylcyclohexane Ethylcyclohexane Propyl
cyclohexane Isopropylcyclohexane tert-Butylcyclohe
xane
DG (ax/eq) (kcal/mol) 1.74 1.79 2.21 2.61 5.50
K 19.5 21.2 43.4 86.0 11,916
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1,1-disubstituted cyclohexanes
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The same principle applies

• The conformation with the largest substituent in
  the equatorial position is favored

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1,2-disubstituted cyclohexanes

• Note the nomenclature cis stands for both
  hydrogens up, trans for one hydrogen up, one
  hydrogen down

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Newman projections
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1,2-dimethylcyclohexane

• Draw all stereoisomers of 1,2-dimethylcyclohexane
  which of them are chiral and which are achiral?

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Cis vs trans
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Question

• Draw all structural isomers of cis- and
  trans-1-isopropyl-2-methylcyclohexane assign R-
  and S-configurations. Which are enantiomers and
  which are diastereomers?

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Which conformations predominate?
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How to determine ring strain ?

• Alkanes are combusted into CO2 and H2O the
  difference in energy release corresponds with the
  stability of the compound

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Heats of combustion (DHc)

• Values are relative to an infinite linear alkane

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Strain energies of cycloalkanes
Strain E per CH2 (DHc-157.5 ) (kcal/mol) 8.8 6.4
1.2 -0.1 0.8 1.1 1.1 0.3 0
Molecule Cyclopropane Cyclobutane Cyclopentane Cy
clohexane Cycloheptane Cyclooctane Cyclodecane Cyc
lododecane (CH2)infinite
Experimental DHc per CH2 (kcal/mol) 166.3 163.9 15
8.7 157.4 158.3 158.6 158.6 157.8 157.5
Strain E from DHc (kcal/mol) 26.4 25.6 6.0 -0.6
5.6 8.8 11.0 3.6 0
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Bicyclic compounds
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Spirocyclic compounds

• Note that the central carbon atom prefers a
  tetrahedral conformation

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Examples

• Examples of naturally occurring and synthetic
  spirocyclic compounds

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Fused bicyclic compounds

• Most prominent in nature are cis-and trans-fused
  decaline systems

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Question

• Why can cis-fused decalins rapidly undergo a
  double chair-chair interconversion, whereas
  trans-fused decalins cannot?

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Examples steroids

• The majority of naturally occurring steroids
  contains the 6,6,6,5-trans-fused skeleton

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Brevetoxin B

• As a result of the trans-fusions, brevetoxin B is
  a linear and more or less flat molecule

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Equatorial vs axial
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Bridged bicyclic compounds
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Solanoeclepin A (UvA project)
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Nomenclature
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A special class adamantanes

• Or the diamond molecules..

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Special adamantanes.
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Other ring systems
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Problems

• Make problems 5.35, 5.37, 5.41, 5.45, 5.49
  (5.32, 5.33)