CHM 251 Organic Chemistry 1
NAME _________________________
Fall 2007 Homework #3
Due: Thursday, October 25, 2007 at 7 am
Print out this assignment and complete all of your work on these pages.
Question #1
The following compound was recently reported in the Journal of Medicinal Chemistry as a key
synthetic intermediate in the synthesis of a potent plant-derived natural product used in the
treatment of cancer.
HO H CH3
H
H
Conformational Interaction
1,3-diaxial (OH and H)
1,3-diaxial (OCH3 and H)
1,3-diaxial (OCH3 and t-butyl)
1,3-diaxial (OCH3 and CH3)
1,3-diaxial (OCH3 and OH)
1,3-diaxial (Ph and H)
1,3-diaxial (Ph and t-butyl)
1,3-diaxial (Ph and CH3)
1,3-diaxial (Ph and OH)
1,3-diaxial (H and C(CH3)3)
1,3-diaxial (H and CH3)
Gauche (t-butyl and OH)
Gauche (t-butyl and CH3)
Gauche (OH and CH3)
OCH3
Ph
H (kcal/mol)
1.3
1.7
3.8
2.3
2.4
1.9
4.1
3.2
3.5
2.7
0.9
2.7
2.3
1.8
(a) Name the structure shown above WITH assignment of R/S configuration for each
stereogenic atom.
(b) Draw the two chair conformations (using the templates provided) of the structure above.
Be sure to LIST all destabilizing interactions and provide a value for total potential
energy (E) for each conformation (more stable and less stable).
more stable
E=
less stable
E=
(c) Find the potential energy difference (H) between the two possible conformations and
use this value to determine the equilibrium constant (Keq) for the chair flip from the
MORE stable to the LESS stable conformation. Do your values for H and Keq make
sense?
Question #2
For the following pairs of molecules, assign the absolute configuration (R or S) to each
stereogenic carbon and indicate the stereochemical relationship (identical, enantiomers,
diastereomers, constitutional isomers, or meso compound) between the two molecules in each
pair.
Pair #1
H
CH3
H
CH3
Pair #2
H
Cl
HO
CH3
Cl
CH3
OH
H
Pair #3
Br
Br
H3CO
OCH3
Pair #4
Br
CH3
H3C
Br
Pair #5
H
H3C
OH
HO
HO
OH
H
CH3
Question #3
(a) Do Worked Problem #5.20 on page 217 of the Jones text. Draw the two chair
conformations for cis-1-isopropyl-2-methylcyclohexane and the two chair conformations
for trans-1-isopropyl-2-methylcyclohexane. Using the data in Table 5.3, record the
predicted energy for each conformation in kcal/mol.
(b) Using SPARTAN, build and calculate the heat of formation for EACH chair
conformation of cis-1-isopropyl-2-methylcyclohexane. Then, build and calculate the heat
of formation for EACH chair conformation of trans-1-isopropyl-2-methylcyclohexane.
NOTE: for the LESS stable isomers, you will need to LOCK the dihedral angles before
calculating the energy.
(c) Report the SPARTAN energy values for each of the chair conformations for cis-1isopropyl-2-methylcyclohexane as well as for trans-1-isopropyl-2-methylcyclohexane.
(you may attach a table of data if you prefer).
(d) Calculate the energy difference between the two chair conformations of cis-1-isopropyl2-methylcyclohexane. How well does this number agree with the prediction from
Worked Problem #5.20 from the Jones text? Explain.
(e) Calculate the energy difference between the two chair conformations of trans-1isopropyl-2-methylcyclohexane. How well does this number agree with the prediction
from Worked Problem #5.20 from the Jones text? Explain.
Question #4
Mirror Images Pharmaceutical Corporation has designed a novel neuromuscular blocking agent
and wants to submit the molecule shown below for patent approval. You are the lead organic
chemist on the legal team and have been asked to investigate certain aspects of stereochemistry in
order to submit a report along with the patent application. Your report requires the following
information:
H
CH 3
O
H
Br
OCH 3
H3CO
H
O
H3C
Br
H
(a) Identify all stereocenters that are not asymmetric carbons in the molecule on the
RIGHT--- label with an SC
(b) Identify all asymmetric carbons in the molecule on the LEFT--- label with an AC
(c) Assign the configuration about all stereocenters and asymmetric carbons on BOTH
molecules --- use E/Z or R/S assignments
(d) Provide the complete IUPAC name for the compound on the LEFT --- identify the
longest chain and any priority groups
(e) Show all polar covalent bonds by writing in the dipole arrow for the molecule on the
RIGHT
(f) Identify the stereochemical relationship between the two molecules (identical,
enantiomers, diastereomers, constitutional isomers, or meso)
Question #5
Identify the following compounds as aromatic, nonaromatic, or antiaromatic. Be sure to fill in all
lone electron pairs and hydrogen atoms to complete the Lewis structures before you begin. In
the process:
(a) Indicate whether lone electron pairs should be included in the calculation of Huckel’s
number (4n +2 electrons) or not. Indicate what types of orbitals the lone pairs reside
in.
(b) Draw the M.O. diagram or Frost circle for each compound.
(c) Explain your assignment of aromatic, nonaromatic, or antiaromatic to each compound.
N
H
S
O