Instructor’s notes

 

Introduction

 

These lab exercises are designed to allow the students to learn some important organic chemistry concepts in a hands-on interactive manner.  The concepts of structural isomers, molecular properties, energies, conformations of ethane, butane, cycloalkanes, especially cyclohexane, substituted cyclohexanes, and biomolecules are explored.  In fact, modules in these lab exercises may take the place of several lectures in organic chemistry in the classroom.   At the discretion of the instructor, these exercises may be used as classroom demonstrations, lab exercises, take-home assignments or combinations of these activities.  These lab exercises can easily take two lab periods and it is important for the students not to rush through the work.  They need to see, feel, experience at their own pace.  Work can be done individually or in pairs to alleviate limited computers in a computer lab.  Although learning how to use modeling software is not the goal primary goal here, students will have learned about the very important tools in molecular modeling while learning basic organic chemistry concepts.  While many modeling software packages are available, PCMODEL is chosen because of its general ease of use, suitability to the teaching and learning tasks at hand, and costs.  Special rates for ACA schools have been arranged with Dr. Kevin Gilbert of SerenaSoft and Indiana University.  For pricing, contact: gilbert@indiana.edu.    The software will run on PC’s and Mac’s and in various operating systems.  Students will need help to find equilibrium ratios and percentages of the conformations.  They will need review in writing equilibrium equations, equilibrium constants, free energy equations and converting ratio to percentages.  From these results, the importance of energy and conformations can be emphasized.  The basic theory is included as a web page.  To facilitate determining percentages without going through individual calculations and detail theories, an Excel spreadsheet is available to use as a calculator or it can be collected as part of the student report.

 

A report sheet handout is available to print and give to students.  You may want to modify the first page on general instructions.  If you would like to have a copy of the report sheet with typical results from this modeling lab, send me an email and please indicate your official position.

 

Materials needed to use this module are:

(1)  PC or MacIntosh computers.  PC’s should be Pentium II or later with Windows 95, 98, or 2000.

(2)  "PCMODEL" from SerenaSoft installed.

(3)  Internet connection to web site Molecular modeling E&H . 

(4)  Support files installed on your local drive.  To download these files, click Support files to access ftp site.  When connected, right click on the "Support files" folder, choose "Copy To Folder" and select your local drive, directory to download. Go to this folder when files are asked for in the exercises.

 

 

A.  1,2-dichloroethene

 

The goal here is to introduce the student to the software with a molecule that is easy to draw and study.

 

 

B.    Conformations of Alkanes

 

1.  Ethane

 

As the lab progresses, you may want to

-        Explain dihedral angles when this term comes up

-        Emphasize MMX energies are generated by the modeling program and are comparable only to other MMX energies

-        Emphasize number of data points and appearance of resulting graphs

-        Explain steric and torsional energies on conformations.

 

The concept of Newman projections on paper can be conveniently introduced at the end of this exercise.  A web page on Newman projection is available.  The percentages of each conformer can be estimated.  For convenience, a link to a spreadsheet is provided so the student can just enter the values to see the estimated percentages.  This spreadsheet is used throughout the rest of these exercises.  If it is desirable for the students to learn the theory, this is also available as a separate link. 

 

2.  !,2-dichloroethane

 

The rotation around the C-C bond here is clearer to students than in the case of butane.  Having studied the conformations of 1,2-dichloroethane, the student can easily extrapolate that butane should have the similar shape of Energy versus Rotation plot.

 

3.  Butane

 

By observing the process of rotations and calculations, students should have a good idea of where the minima and maxima are with respect to rotation.  They can always see this again by repeating this and keep the step size small.  An understanding of butane conformations is used to study cycloalkanes.

 

C.    Cycloalkanes

 

1.  Flat cycloalkanes

 

By examining the adjacent carbons of flat cycloalkanes, the student will see that each pair of carbons is in a conformation similar to that of the highest energy conformation of butane, the one with eclipsed methyls.

 

2 - 5. Cyclopropane, Cyclobutane, Cyclopentane, Cyclohexane

 

Cyclopropane and the other theoretically flat cycloalkanes can be studied conveniently in molecular modeling.  By comparing the properties and energies of the flat and puckered conformations, the student can gain a better appreciation for the angle, torsion and steric strains involved.

 

D.  Cyclohexane conformations

 

The important cyclohexane conformations – flat, half chair, boat, twist boat, chair - are studied in more detail here.

 

E.  Cyclohexane – Axial and Equatorial positions

 

The relationships of groups on “top or bottom” and “axial or equatorial” of the ring is examined.  Students will have a good understanding of how they are related.

 

F.     Monosubstituted Cyclohexanes

 

Students will gain an understanding that, in general, equatorial groups are more stable than axial groups on cyclohexane.  Students may be assigned to do only certain ones to save time.  The instructor may want to make the part of finding equilibrium distributions optional.

 

G.    Disubstituted Cyclohexanes

 

The misconception that trans is always more stable than cis for dialkylcyclohexanes is dispelled here.  The student will see that, as in part F, it is equatorial versus axial that is important.

 

H.    Local and Global Minima

 

Finding the lowest energy conformation, Global minimum, is often a difficult task.  When software finds a local minimum, it may not look any more as incremental small changes lead to higher energies.  For example, minimizing the boat cyclohexane only gives the twist boat as low energy conformation.  Many strategies are used including making large Cartesian changes in atom coordinates and rotations.  A global search will give the chair conformation for cyclohexane as the global minimum.

 

I.      Biological molecules

 

By looking at a protein segment, student will gain an appreciation of the three-dimensional shape of large molecules.  In this case a spiral with a hole in the middle when viewed from the top or bottom.  Viewing real molecules, “myoglobin” and a “HIV DNA strand” from the protein data bank further emphasizes the real world applications of molecular modeling.

 

Other viewers and explorers are available over Internet for biomolecules.  Protein Explorer is available at http://www.umass.edu/microbio/chime/explorer/index.htm.  Protein Explorer runs online from its web site and requires Netscape Navigator and Chime to work.  Another viewer, Rasmol, is available at http://www.umass.edu/microbio/rasmol/.   Rasmol allows you to download pdb files and view them later on your computer.

 

J.     Structural Isomers or identical molecules

 

Students often have trouble recognizing that “different looking” drawings of the same molecule are possible.  This creates various problems such as writing isomers of a given molecular formula.  Students who do not learn this basic concept early will encounter much difficulty throughout the two semesters of organic chemistry.  This module hopefully will give students a good sense of the three dimensional nature of molecules.  And by actually manipulating the molecules themselves, it’s a lesson they won’t easily forget.  Further work on this can involve additional assignment (to be added) and have students determine if they are or are not the same by bond and molecule rotations.  Alternatively, the instructor as introduction to the module can use this exercise as a demonstration.  The advantage of this exercise over holding up large models is that everyone can see the same perspective with molecular modeling.