CHM 251 Organic Chemistry 1

CHM 251 Organic Chemistry 1 NAME ______

Fall 2005 Homework #2

Due: Friday, October 21, 2005 by 5:00 pm

Print out this assignment and complete all of your work on these pages.

Question #1

The following sets of question pertain to intermolecular forces:

(a) Provide a valid structure for each of the following molecules and then, arrange the compounds in order of increasing boiling point. Briefly explain your ordering being sure to indicate the type and relative magnitude of intermolecular interactions (e.g. VDW interactions, dipole-dipole, and hydrogen bonding) that exist in each case. You may want to consult the Aldrich catalog, an MSDS, or go to chemfinder.com.

1. 2,3-dimethyl-2-butanol

2. 2-amino-1,3-propanediol

3. n-hexane

4. ethyl 3-oxobutanoate (a.k.a. ethylacetoacetate)

5. dichloroethanoic acid (or if you prefer, dichloroacetic acid)

6. methyl butyl ether

(b) Using your knowledge of intermolecular interactions, predict the order of elution of spots on a TLC plate (silica gel – you may have to look up the structure if you don’t know what it is) from smallest to largest Rf value for the following series of compounds in the presence of a methanol mobile phase. Draw a representative TLC plate that shows the
relative Rf value for each compound and briefly explain the ordering. You’ll have to draw the structure for each before evaluating its potential IM forces.

(c) A common organic chemistry laboratory technique is called extraction. This technique can be used to extract polar organic molecules (e.g. aspirin) from aqueous solutions into an organic solvent (e.g. diethyl ether). Shown below is a separatory funnel with two immiscible liquids, ether and water.

1.
Which layer is which?

2. If you had two solutes (like aspirin and NaCl), in which layer would you find each solute? Is the separation exclusive? Explain by listing the potential intermolecular interactions that can occur in each layer between the solute and the solvent. You should draw pictures to help represent these interactions.

(d) Normally, the drug shown below is much more soluble in lipid-like solvents (e.g. benzene) than it is in water. However, its water solubility INCREASES considerably when the aqueous solution contains moderate amounts of strong acid (e.g. in the stomach) as shown by the reaction below. Explain the solubility differences.

Question #2

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.

Conformational Interaction / DH (kcal/mol)
1,3-diaxial (OH and H) / 1.3
1,3-diaxial (OCH3 and H) / 1.7
1,3-diaxial (OCH3 and t-butyl) / 3.8
1,3-diaxial (OCH3 and CH3) / 2.3
1,3-diaxial (OCH3 and OH) / 2.4
1,3-diaxial (Ph and H) / 1.9
1,3-diaxial (Ph and t-butyl) / 4.1
1,3-diaxial (Ph and CH3) / 3.2
1,3-diaxial (Ph and OH) / 3.5
1,3-diaxial (H and C(CH3)3) / 2.7
1,3-diaxial (H and CH3) / 0.9
Gauche (t-butyl and OH) / 2.7
Gauche (t-butyl and CH3) / 2.3
Gauche (OH and CH3) / 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).

(c) Find the potential energy difference (DH) 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 DH and Keq make sense?

Question #3

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.

Question #4

Complete the following Exercises from the “Molecular Modeling Workbook for Organic Chemistry”. Be sure to answer ALL questions in each exercise as well as to generate any required graphs (use EXCEL). Please organize answers for easy reading by the professor.

Also, compose a BRIEF conclusion for each of these experiments. Attach your answers/graphs to the back of the homework assignment.

(a) Experiment 4.1 “Enantiomers” page 68

(b) Experiment 16.11 “DNA Base Pairs” page 230

(d) Experiment 5.7 “Electronic Control of Ring Conformation” page 80