Experiment 3: STEREOCHEMISTRY AND MOLECULAR MODELING OF CYCLOALKANES
OBJECTIVES • To learn how to construct variouscyclohexane conformers using handheld molecular models and the HyperChem molecular modeling program. • To determine the lowest energyconformation of the molecule by performing energy minimization calculations with HyperChem. • To examine the individual factors that contribute to the overall energy of the system.
Conformations of Monosubstituted Cyclohexanes • Although ring-flip occurs rapidly, the two conformers are not EQUAL! This conformer has more diaxial interactions, therefore is higher in energy!
1,3-Diaxial Interactions • Q: What causes the difference in energy between the conformers? • Steric strain due to 1,3-diaxial interactions. • Q: What is a 1,3-diaxial interaction? • Atoms on C1 are too close to those on C3 and C5!
Disubstituted Cyclohexanes • In disubstituted cyclohexanes, BOTH substituents experience steric interactions with axial groups. • There are two isomers of 1,2-dimethylcyclohexane, cis and trans. • Must consider the sum of all interactions.
Conformational Analysis of Disubstituted Cyclohexanes • Q: What is conformational analysis? • Assessing energy of cycloalkane by summing all steric interactions. • Q: Why is it important? • Can help predict which conformations are more favorable and more likely to exist.
OVERVIEW • Sketch cyclohexane structures given the IUPAC name. • Identify spatial relationship (cis/trans) between methyl groups on each structure using models. • Rank stability of conformer before and after ring-flip. • Use HYPERCHEM program to determine how much of each type of energy contributes to the overall energy of the molecule. • Measure bond angles before and after geometry optimization to determine how angles change during energy minimization.
Part A: Conformational Stability with Models • Using provided molecular models, build disubstituted cyclohexanes with given substitution pattern. • Sketch cyclohexane in Table 3.1. • Q: Are the methyl substituents cis or trans to one another? • Q: Is this the most stable conformation as it is currently built, or would it be more stable after the ring flip occurs?
Disubstituted cyclohexane Cis or Trans? Most stable conformation? Structure 1,2-dimethylcyclohexane, both groups axial trans No: ring flips to more stable eq/eq conformer 1,2-dimethylcyclohexane, both groups equatorial 1,2-dimethylcyclohexane, one axial, one equatorial 1,3-dimethylcyclohexane, both groups axial 1,3-dimethylcyclohexane, both groups equatorial 1,3-dimethylcyclohexane, one axial, one equatorial 1,4-dimethylcyclohexane, both groups axial 1,4-dimethylcyclohexane, both groups equatorial 1,4-dimethylcyclohexane, one axial, one equatorial Table 3.1 Remember to include methyl substituents in the proper place and all of hydrogen atoms!
Part B: Conformational Analysis: HYPERCHEM • E total = E bond stretch + E angle strain + E torsional strain + E VDW • The HyperChem program will allow us to build the structure, then will perform energy minimization calculations in an effort to find the lowest energy conformation. • We can keep track of the results by keeping a log of the file, which can be viewed to retrieve the desired results. HyperChem refers to this as “dihedral” strain
Part B: Conformational Analysis: HYPERCHEM • HyperChem will perform 2 kinds of calculations: • SINGLE POINT • determines the total energy of the molecule for a fixed geometry • GEOMETRY OPTIMIZATION • determines the lowest energy conformation by altering the molecular geometry.
Part B: Conformational Analysis: BOND ANGLES • After the single point calculation has been performed, two bond angles will be determined: • These angles will be measured again after the geometry optimization has been performed.
Part B: Using HyperChem… • Build model with HyperChem. • Start Log. Save to DESKTOP. Give file name such as “cis12sp”. • Perform Single Point calculation. • Stop Log. • Open log file on DESKTOP. Record all required values. • Measure bond angles. • Deselect all atoms (NO GREEN!) • Start Log. Save to DESKTOP. Give file name such as “cis12go”. • Perform Geometry Optimization. • Stop log. • Open log file on DESKTOP. Record all required values. • Measure bond angles. • START OVER with next molecule!