Integrating Computational Molecular Modeling into the

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Integrating Computational Molecular Modeling into the Powered By Docstoc
					                          Chemisty 344 Molecular Modeling
                                 Student Feedback
                                    Spring 2007


Letter to Chemistry 344 Students Soliciting Feedback:

Dear Chem 344 Students,

This semester is the fifth time that we have included a molecular modeling lab as part of
Chem 344. We have made significant changes, hopefully improvements, each time, and
we hope to continue improving on the molecular modeling experience that students get in
this course. Your comments on your experience this semester would be very helpful.

If you would be willing to take a moment and provide your comments by return e-mail,
we would appreciate that. We are interested in your candid opinions, and would be
happy to receive them anonymously (i.e. from an e-mail source not identifiable with you)
if you have any concerns about identifying yourself.

Separately, we welcome any comments you have on other aspects of your Chem 344
experience now that you've completed the course.

Wishing you well on your finals and a safe and enjoyable summer.



Student Comments Expressing an Overall Favorable Opinion and Only Favorable
Remarks:

I thought the MM lab was one of the most valuable modules we did all semester. For me,
it was very helpful to see the 3-d orientation of the molecules, especially the transition
states, in order to visualize the various mechanisms (especially Diels alder).

I thought the molecular modeling lab was overall an effective way of teaching the
intended concepts. Using computers to model otherwise difficult-to-visualize situations
was a refreshing change. Whatever changes have been made over the years appear to
have been quite beneficial.

I felt that lab was a great learning experience. I learned the mechanisms during
discussion and then executed the syntheses in lab. The molecular modeling lab was fine.
It took the four hour periods, but did not have outside work which was a nice change.
The software helped me visualize the structures.

Overall, I found the molecular modeling lab to be very valuable. Although tedious at
times, Spartan was a great exercise to demonstrate the behavior of molecules. Computing
the atomic descriptions of the molecular systems was a cool way to look at them. I think
the best part of the lab was that it made the systems much simpler to think about, which is
a great benefit.

I thought that the molecular modeling lab was fine to include in the course. It was a nice
break from doing the same thing every night and it helped explain some things that I
probably wouldn't have gotten if we did not do that lab. I would keep it in the course and
I can't think of anything in particular to improve.

I thought the MM lab was good. It helped to reinforce the reasoning behind certain
reaction mechanisms (eg EAS, SN1/2). It was also a nice break from wet chemistry.


Student Comments Expressing an Overall Favorable Opinion along with
Complaints, Criticisms or Suggestions for Improvement:

The molecular modeling lab is very good in regards to understanding the stereochemistry
of different molecules and why there are different energies associated with different
conformations. However, some parts of the lab were confusing- stuff we had never
learned before- most specifically HOMO and LUMO. The HOMO/LUMO exercise
seemed to be merely inputting numbers, not understanding what we were doing or why
we were doing it.

I thought the molecular modeling lab was a great change of pace. It allowed me to get a
better view of how certain reactions worked, and reinforced some of the concepts taught
during 343 and 345. My only complaint is how the basics of the program were taught. A
lot of time was wasted by not knowing how the program worked. My TA had suggested
that next time it would be better to have a projector in the computer lab so that one
of the TAs could go through a little tutorial before the actually lab work. Other than that,
I thoroughly enjoyed the molecular modeling lab.

The molecular modeling was an interesting lab, except the molecular orbitals were really
confusing. It is probably because it has been a while since we've gone over molecular
orbitals, but it made no sense and I did not learn anything from that particular part. The
other parts, especially with transition states and energy was interesting though.

I feel it helped me understand the mechanisms. Maybe do more of an intro on the sigma
and pi orbitals. That was the most confusing part.

My one comment with the molecular modeling lab is that the Solomon values should be
posted on the website. I am in the honors section, which uses the Jones textbook, and
although I knew several people with the Solomon book it was surprisingly hard to get a
hold of. This only affects a few people, but it would have made things easier. Otherwise I
did find this lab helpful. Maybe it would be good to do a brief discussion about how the
molecular orbitals in the program relate to the hand drawn depictions of diene and allyl pi
MO systems.
The Molecular Modeling lab was very useful in understanding the reactions that it
covered. It was nice to have a short break from the lab procedures. The only complaint I
had about the lab was that the program sometimes experienced an error, making it
necessary to start the exercise over. Thanks for a great semester!!!

The instructions were clear and easy to follow. I enjoyed using the program, but I am not
sure what I was really supposed to take out of it because scratching the service of
molecular modeling. I think there should be one more part added to it where you design
your own molecule and answer some questions about it or something? Overall, I enjoyed
it more then most labs.

I liked the molecular modeling lab and it was pretty easy to pick up on quickly. [My TA]
mentioned that a projector would be helpful so there could be a quick tutorial for the
whole class rather than in small groups and I also think it would be beneficial.

I felt that the molecular modeling lab was a bit long for the allotted time because we did
not really know how to work the program. But other then that I liked it, so perhaps just a
little tutorial on how to use the program before hand.

The molecular modeling unit was extremely useful as it building on existing skills that
were taught in the course as well as gave some exposure to future course skills and
experiments. As with most computer based tasks, they can become quite laborious after a
while of working on the computer for a long time. This exhaustion that at least I felt after
a few hours of working on the system lead to less learning of the material and program
and just a task to complete. After my exhaustion was felt, I removed myself from the
class period and continued the task the next morning at which point I was able to focus
more and retain quite a bit more of the concepts. So with that suggestion, I would maybe
say that if you schedule two class periods for it make them shorted in the syllabus, but
make other times in the lab reserved for students to come in on outside times on a
different day to finish another shorter portion. so that more information can be retained.
Reserving outside times, outside of regular lab period would be helpful.



Student Comments Expressing a Neutral or Negative Overall Opinion with Negative
Opinions Offsetting any Positives:

I didn't think that the molecular modeling lab was bad, however I don't feel like I learned
too much from it. I feel that there was an emphasis on HOMO/LUMO topics, but we
didn't learn anything about these topics in our discussions, and barely brushed on them in
343/345. I'm not sure if the HOMO/LUMO was most informative part of the lab module.
I did think that having the molecular modeling lab was a good break from always having
a "wet" lab, but I think a lot of the process was the students just trying to fly through it as
fast as possible to get the necessary "reactions" done. Not sure if these comments are
much help, but I thought I'd let you know. Have a good summer!
I had mixed feelings about the molecular modeling lab. I liked the part on the Diels-Alder
reaction because before talking about it in lab, I was very confused about endo/exo
prodcuts. After doing the lab, now I really understand the difference between the endo
and exo products and how it can be explained via HOMO and LUMO. The rest of the lab
I thought was alot of busy work. It didn't really increase my knowledge of reactions.
Maybe to make the lab better some of the sections can be removed, and the lab can be
made to be only 1 lab period long?

The molecular modeling lab was a bit frustrating for me because it felt so detached from
the other lab work we had done. I did enjoy the computer program and imaging, but I felt
that it was out of place in this semester. If it was placed at the beginning or very end, it
might have been more beneficial. Hope this helps!

I thought that the first day of the molecular modeling lab was fine, I felt like I understood
the program and that it worked out well. The second day however was dreadful nothing
worked out the right way, the computer kept giving me an error message (even after
switching machines multiple times) and I was there for almost an hour longer than some
of the other students. I think that it would work much better as a tutorial type thing were
you are asked to make the structure and the computer verifies if it is correct and help to
lead the students through the procedure a little more. I don't know if this sort of idea
would be feasible but I think that would have helped a lot. Thank you for your time.


I think the lab covers the material well and helps explain certain mechanisms that we
have in the lab. It gives another visual representation and also helps think in terms of
energy and stability. With that said, it also was very frustrating and I think the above
comments are completely in retrospect. I disliked the lab at the time.

To be honest, I didn't really get that much out of the molecular modeling lab. The only
really worthwhile thing was that it prepared us for the Diels-Alder lab.

The molecular modeling lab was important to learn about in concept...however I don't
feel that students got much out of it. Granted we aren't proficient with the program, the
stuff we were asked to look for (energy differences) was so basic that the computer
program didn't really help with the concepts because we knew them. The lab module was
extremely long and could possibly be cut to one day of lab instead of an entire week...
Two Undergraduate Experiments In Organic Polymers: the Preparation of
Polyacetylene and Telechelic Polyacetylene via Ring-Opening Metathesis
Polymerization

Eric J. Moorhead; Anna G. Wenzel*
Joint Science Department; Claremont McKenna, Pitzer and Scripps Colleges;
Claremont, California 91711

I. Experiment 1: Preparation of Conductive Polyacetylene
IA. Reagents
  Unless otherwise indicated, all reagents were used as received without prior purification.
  The reagents required (per group) for each experiment are:
  1. 1,3,5,7-cyclooctatetraene (COT; 0.5 mL, 0.47 g, 4.5 mmol; CAS [629-20-9];
     commercially available from ChemSampCo. ($1.23/mmol))
     IMPORTANT! 1,3,5,7-cyclooctatetraene (COT) readily forms peroxides upon exposure
     to air. To ensure safe handling, be sure to either buy commercial product stabilized
     with a small amount of hydroquinone or add stabilizer prior to storage. COT reagent
     bottles were flushed with argon and stored in the fridge between uses. Regular peroxide
     testing is recommended.
  1. Grubbs 2nd Generation Catalyst (benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-
     imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium; 10 mg, 11.8 x 10−3
     mmol; CAS [629-20-9]; commercially available from Aldrich ($179/mmol))
  2. anhydrous methanol (~5 mL); commercially available from Fisher Scientific
  3. iodine (~6 g/250 cm3 of doping container volume; CAS [7553-56-2]; commercially
     available from Fisher Scientific) Note: multiple experiments can be doped together
  4. 80-200 mesh alumina, adsorption (~300 mg; CAS [1344-28-1]; commercially available
     from Fisher Scientific. Alumina was flame-dried under vacuum (1 torr) and stored in an
     oven (130 °C) prior to use.

IB. Equipment and Supplies (per group)
  1. Two, 3-mL conical vials equipped with a caps fitted with Teflon-faced septa
      (commercially available from Chemglass; $16.24 ea). This vial is a component in most
      microscale lab kits.
      *Note: one vial will be used for the reaction, the other for storing the filtered COT. If
      Experiments 1 and 2 are to be performed concurrently, the same vial can be used to
      store the COT to be used in both reactions.
  2. 1 glass microscope slide
  3. 9-inch glass pipettes (3 per group)
  4. 6-inch glass pipette (1 per group)
  5. rubber pipette bulbs (minimum of 2)
  6. 1-mL syringe with stainless steel needle
  7. glass wool
  8. voltmeter with test leads capable of measuring up to 20 MΩ
  9. small vacuum desiccator or wide-neck Schlenk tube (commercially available from
      Soham Scientific, http://www.sohamscientific.co.uk/schlenktube.html; prices vary)
  10. Schlenk line with either argon/vacuum or nitrogen/vacuum capability
  11. vent needle (e.g. 1.5” 18G needle)


                                                                                            S1
12. Optional: 25 oz. plastic container (available at most grocery stores). While not required,
    such a container, when flushed with argon, can be used for plate transport outside the
    glove bag.
13. Glove bag
    Note: as a more economical, user-friendly alternative, a glove bag can be constructed
    from the following materials (Figure 1): one 2.5 or 5 gallon Ziploc bag (available at
    most grocery stores), a small ring stand, one large binder clip (2.54 cm), electrical tape,
    and ¼ -in Tygon tubing connected to an argon tank. To assemble, place the small
    ringstand in the plastic bag and clip it to the bag (Figure 2). The bag opening should be
    pointed upwards. Next, on the side of the bag nearest the ringstand: poke a small hole
    two-thirds of the way up the bag and insert the Tygon tubing. Secure with electrical
    tape. Be sure to flush the bag with argon for 15 minutes prior to use. The greater
    density of argon relative to air will allow the students to readily manipulate their
    polymer plates with minimal difficulty.

   Figure 1. Components for glove bag setup




   Figure 2. Assembled setup




                                                                                            S2
 IC. Before Lab
 Wash the microscope slides with either acetone or isopropanol and wipe dry with a
 Kimwipe. Dry the slides, 1-mL syringe, and the pipettes in the oven prior to class (130 °C;
 min. 1.5 h). Flush the glove bag with argon 15 minutes prior to use. Flame-dry the alumina
 under vacuum (1 torr) and place in an oven (130 °C).

II. Experiment 2: Preparation of Telechelic Polyacetylene
IIA. Reagents
   Unless otherwise indicated, all reagents were used as received without prior purification.
   The reagents required (per group) for each experiment are:
   2. 1,3,5,7-cyclooctatetraene (COT; 0.75 mL, 6.7 mmol; CAS [629-20-9]; commercially
      available from ChemSampCo. ($1.23/mmol))
      IMPORTANT! 1,3,5,7-cyclooctatetraene (COT) readily forms peroxides upon exposure
      to air. To ensure safe handling, be sure to buy commercial product stabilized with a
      small amount of hydroquinone or add stabilizer prior to storage. COT reagent bottles
      were flushed with argon and stored in the fridge between uses. Regular peroxide testing
      is recommended.
   3. Grubbs 2nd Generation Catalyst (benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-
      imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium; 10 mg, 11.8 x 10−3
      mmol; CAS [629-20-9]; commercially available from Aldrich ($179/mmol))
   4. anhydrous methanol (150 mL); commercially available from Fisher Scientific
   5. ACS grade dichloromethane (9 mL); commercially available from Fisher Scientific
   6. deuterated dichloromethane (0.5 mL); commercially available from Cambridge Isotope
      (10 x 1g, $46.20)
   6. 80-200 mesh alumina, adsorption (~300 mg; CAS [1344-28-1]; commercially available
      from Fisher Scientific. Alumina was flame-dried under vacuum (1 torr) and stored in an
      oven prior to use.
   7. cis-2-butene-1,4-diol bis(tert-butyldimethylsilyl) ether (0.8 mL, 2.2 mmol;
      CAS [132835-15-5]) *Not commercially available: see Section IID for experimental

IIB. Equipment and Supplies (per group)
1.    5-mL conical vial equipped with a cap fitted with a Teflon-faced septum (commercially
      available from Chemglass; $16.24 ea). This vial is a component in most microscale lab
      kits.
2.    spin vane
3.    3-mL conical vial equipped with a cap fitted with a Teflon-faced septum (commercially
      available from Chemglass; $16.24 ea). This vial is a component in most microscale lab
      kits.
4.    Two, 1-mL syringes equipped with stainless steel needles
4.    9-inch glass pipette
5.    6-inch glass pipette
6.    Glass wool
7.    Beaker (250 mL)
8.    Stirbar
9.    Büchner funnel with filter paper
10. vacuum flask (250 mL)



                                                                                          S3
11.       Neoprene adapter (for Büchner funnel filtration)
12.       Schlenk line with either argon or nitrogen capability
13.       NMR tube
14.       Quartz UV-vis cuvettes (1-cm path length)

IIC. Instrumentation Used in this Experiment
1. 1H-NMR (Bruker AC300, w/Tecmag Upgrade, wide-bore probe)
2.    FT-IR (Nicolet Avatar, equipped with a Zn-Se pellet plate)
3.    UV-vis (Agilent Model #8453)

IID. Before Lab
  Prepare cis-2-butene-1,4-diol bis(tert-butyldimethylsilyl) ether (see experimental below).
  Place the syringes, spin vane, and conical vials into an oven to dry (130 °C ; min. 1.5 h).
  Flame-dry the alumina under vacuum (1 torr) and place in an oven (130 °C).


     *Preparation of cis-2-butene-1,4-diol bis(tert-butyldimethylsilyl) ether:†




  Required Reagents:
  1. cis-1,4-dihydroxybutene (4.9 mL, 60.3 mmol, 1.0 equiv; CAS [6117-80-2];
       commercially available from Acros (25 mL/$14)
  2. tert-butylchlorodimethylsilane (TBSCl; 19.0 g, 126 mmol, 2.1 equiv; CAS [18162-48-
       6]; commercially available from Acros (100 mL/$80.40)
  3. imidazole (17.2 g, 253 mmol, 4.2 equiv); CAS [288-32-4]; commercially available
       from Acros (250 g/$49.50)
  4. anhydrous tetrahydrofuran (450 mL)
  5. 1% aqueous solution of HCl (150 mL)
  6. saturated aqueous sodium bicarbonate solution (150 mL)
  7. saturated aqueous sodium chloride solution (brine; 75 mL)
  8. diethyl ether (75 mL + any additional needed for glassware transfers)
  9. sodium sulfate (~10 g)
Procedure: to a flame-dried, two-necked 1-L flask under an atmosphere of nitrogen, cis-1,4-
dihydroxybutene (4.9 mL) was added to anhydrous tetrahydrofuran (450 mL). Imidazole
(18.0 g) was added with stirring. TBSCl (19.0 g) was then added portion-wise over a 5-
minute period. A cloudy white precipitate was observed to form. The reaction was allowed to
stir at ambient temperature overnight (15 h). At this point, 100% conversion was observed
via TLC (silica gel 60 plates, product Rf = 0.65 in 5% ethyl acetate in hexanes, KMnO4 TLC
visualization). The salts were removed from the reaction mixture via Büchner funnel
filtration, using diethyl ether (75 mL) to rinse the salts and ensure complete transfer. The
filtrate was then transferred to a separatory funnel and washed with an aqueous solution of
1% HCl (2 x 75 mL), saturated aqueous sodium bicarbonate (2 x 75 mL), and brine (1 x 75
mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated

†
    Procedure adapted from: Jones, K.; Storey, J. M. D. Tetrahedron 1993, 49, 4901-4906.



                                                                                           S4
in vacuo to afford the product as a colorless liquid in quantitative yield. The product was
purified via vacuum distillation (bp 130 °C at 5.7 torr) to afford 18.1 g of cis-2-butene-1,4-
diol bis(tert-butyldimethylsilyl) ether (95% yield).


III. Student Handouts and Procedures
Student experimental handouts, prelabs, and report instructions have been provided on the
following pages. In these, Experiments 1 and 2 were performed concurrently. Notes to the
instructor have been delineated as alphabetic superscripts and are listed at the end of the
experimental instructions section.




                                                                                           S5
        Ring-Opening Metathesis Polymerization (ROMP):
Preparation of Polyacetylene from 1,3,5,7-Cyclooctatetraene (COT)




Experiment 1:

                                                       Polyacetylene (mixture of Z and E alkenes)


Experiment 2:




Prelab Reading.
1.) COT Polymerization:
    *Scherman, O. A.; Grubbs, R. H. Synth. Met. 2001, 124, 431-434.
2.) Olefin Metathesis:
    *Casey, C. P. J. Chem. Ed. 2006, 83, 192-195.
3.) 2000 Nobel Article:
    *http://nobelprize.org/nobel_prizes/chemistry/laureates/2000/chemadv.pdf

Experiment Overview.        Intrinsically conducting polymers (ICP’s) have long garnered
interest due to their potential use in a wide variety of applications such as polymer light-
emitting diodes, electrostatic dissipation (ESD) materials, and charge storage devices.
Organic ICP’s are highly conjugated molecules with a “quasi-infinite” system of π bonds
extending over a number of recurring monomer units. This feature results in materials with
directional conductivity, the strongest of which lie along the axis of the chain (1).

ICP’s were first investigated in the mid 1970’s, when the first polymer capable of conducting
electricity—polyacetylene—was prepared by Shirakawa (by accident!) (2). The conductivity
of doped polyacetylene has since been found to be comparable to the conductivity of the best
natural conductor, silver, making it highly sought after for commercialization (3). The Nobel
Prize in Chemistry in 2000 was awarded to Alan J. Heeger, Alan G MacDiarmid, and Hideki
Shirakawa for this work.

Despite its potential, the production of polyacetylene ICP’s has encountered several barriers
to widespread commercialization. Polyacetylene cannot be readily prepared on large scale by
the direct polymerization of acetylene, as it is a highly flammable gas that can uncontrollably
oligomerize at high concentrations. Indirect preparation can be achieved via the construction
of a precursor polymer, which can then be subsequently converted to polyacetylene (4).
Unfortunately, this route requires the extrusion of large molecular fragments and offers poor


                                                                                                    S6
atom economy. In addition, some of these routes afford potentially explosive byproducts,
presenting serious safety considerations. An ideal route to polyacetylene is one that
overcomes these issues while simultaneously providing architectural control to enable ease of
characterization and processing.

In 1988, Grubbs and Klavetter reported that polyacetylene derivatives could be readily
assembled via the ring-opening metathesis polymerization (ROMP) of
1,3,5,7-cyclooctatetraene (COT, 2) (4,5). ROMP typically utilizes the relief
of ring strain to promote reaction rate and high yield. COT, however, has an
extremely low ring strain of only 2.5 kcal/mol (6). Early metathesis
reactions of COT compensated for this by using highly reactive tungsten
catalysts. Unfortunately, these catalysts are highly air and moisture-sensitive
and cannot be utilized outside of an inert atmosphere glovebox. An
alternative is to use ruthenium-based catalysts, which are more stable to ambient conditions
and can be readily handled on the benchtop. Early Grubbs catalysts, such as first-generation
catalyst 4, proved poorly reactive with COT. It was not until the development of the more
reactive catalyst 1 in the late 1990’s that COT could be polymerized effectively by
ruthenium-based catalysis (7). In this lab, you will be performing two experiments. In the
first, you will be utilizing catalyst 1 to polymerize COT directly onto a microscope slide; you
will then attempt to generate a conducting polymer by doping it with iodine. In the second
experiment, you will use catalyst 1 polymerize COT in the presence of TBS-protected cis-2-
butene diol (3). Compound 3 acts as a chain-transfer agent (8) to cleave the polymer from the
catalyst, resulting in polymers 10-20 alkene units in length. The resulting solid can be
regarded as a telechelic polymer (9), possessing terminal OTBS groups that can be
deprotected and derivatized for a variety of applications.

Experimental Instructions.
Day 1. From the oven, obtain: a 5-mL conical vial equipped with a spin vane and two, 3-mL
vials. While they are still hot, take the vials over to the hood and attach a cap equipped with a
Teflon septum to each vial. Stick a needle attached to an argon (or nitrogen) line through
each septum. Next, take a 6” pipette and place a small plug of glass wool at the bottom of it.
Fill the pipette with about 1 cm-worth (~300 mg) of alumina from the oven. Allow the
alumina in the pipette to cool. While the glassware is cooling, take a washed microscope
slide and a pipette out of the oven and place them, along with a pipette bulb, in the “glove
bag” provided. The glove bag has been placed under an atmosphere of argon in preparation
for Experiment 1.
Add 5 mg of 1 (5.9 x 10−3 mmol) to one of the 3-mL vials and 10 mg of catalyst 1 (11.8 x10-3
mmol) to the 5-mL vial. Make sure that you add the catalyst quickly to each vial to minimize
exposure to air. To ready your monomer, slowly add ~1.5 mL of COT (2) to the top of the
pipette with the alumina plug. Allow the COT to run through the plug into the third, empty 3-
mL vial. Be sure to cap your COT when it is not in use! (Note: the alumina plug removes any
water and/or stabilizers from the COT that might interfere with your reaction)

Experiment 1: prepare a syringe with 0.5 mL of COT (4.44 mmol). Detach the 3-mL vial
containing 5 mg of 1 from the argon line and bring both it and the syringe to the glove bag in
a dimmed hood.1 Holding the vial under the argon atmosphere, insert a vent needle. Then,


                                                                                              S7
quickly add the COT to your catalyst. Remove both needles and shake the vial vigorously to
mix. You will need to move efficiently here, as polymerization will begin to occur rapidly.
Holding the vial in the bag under the argon atmosphere, remove the lid. Then, using your
oven-dried pipette, evenly transfer the polymer-COT mixture to the microscope slide. It is
important to transfer your entire reaction mixture to the slide to ensure adequate polymer thickness.
Within minutes, the polymer mixture will gel onto the slide. Allow 20 minutes for your
polymerization to complete.2 Record any observations in your notebook. Begin Experiment 2.

Experiment 2: Preheat an oil bath to 55 °C. During this time, ready two 1-mL syringes: one
that contains 0.75 mL of COT (6.7 mmol)3 and another with 0.8 mL of alkene 3 (2.2 mmol).
Sequentially add the COT and alkene 3 to the catalyst in the 5-mL conical vial with stirring.
Immerse your vial into the oil bath overnight (12-18 h).4 Once heating, the needle to the
argon line can be removed. To protect the polymer from light exposure, hood lights should
be shut off and/or the vial shielded with aluminum foil for the duration of the reaction.
Record any observations in your notebook.
Experiment 1 continued:   take your microscope slide out of the glove bag and gently rinse it
with a few milliliters of anhydrous methanol (~5 mL) via pipette to remove any unreacted
COT, etc.5,6 Place the slide back into the argon bag to dry. In the meantime, add ~6 g of
iodine to the bottom of a small vacuum desiccator.7 Insert your polymer slide into the
apparatus and seal it. Evacuate the desiccator under high vacuum and refill it with argon.
Repeat this procedure twice. Finally, place the flask under vacuum and seal it—this is called
static vacuum. Cover the desiccator with aluminum foil and leave it under static vacuum for
1.5-2 h.8 If you return to find your polymer has some metallic gold coloring, congratulations!
You have just changed plastic into a conductor! Note all observations in your notebook.
Leaving your desiccator covered with aluminum foil, refill it with argon and seal it. Detach
the desiccator from the Schlenk line and place it in the glove bag. Make sure the lights are
dimmed! Using a two-point resistance probe, try to measure the resistance of your polymer.
We’re not doing anything fancy here, so anything less than infinite resistance is a success!9
Make note of your polymer’s resistance in your notebook. This concludes Experiment 1; all
continuing instructions refer to Experiment 2.

Day 2.  After 24 h, obtain a 400-mL beaker with a stirbar and add 150-mL of methanol to it.
Place the beaker onto a stirplate and begin stirring. Next, remove your vial from the oil bath
and wipe the outside of it to remove any oil residue. Uncap your vial and pour its contents
into the stirring methanol. Rinse your vial with 6 mL of dichloromethane to ensure the
complete transfer of your polymer into the beaker. Allow the methanol mixture to stir for a
few minutes. While it is stirring, set up a small Büchner funnel attached to a filter flask. Once
assembled, vacuum filter your polymer mixture to collect your product as a dark brown solid.
Place your polymer into a small tared vial, and then allow it to dry in a vacuum desiccator
until the next lab period.10

Day 3.  Today is the day that you get to play with your telechelic polymer! Take the vial
containing your product out of the vacuum desiccator and weigh it to get a yield (you will
calculate the percent yield later). The following three tests must be performed on your COT-
OTBS polymer:
    1) IR Spectrum. Take an IR spectrum of your polymer via pellet (Zn-Se pellet plate).
        Two peaks that you should be looking for: a peak at 743 cm−1, which can be


                                                                                                  S8
        attributed to a cis C-H out-of-plane vibrational mode, and a peak at 1011 cm−1, which
        is due to the trans C-H mode (10).11 Print out a copy of your IR spectrum for your
        report. As this is a non-destructive test, you can recover much of your polymer from the
        plate. Be sure to wash both the plate and press thoroughly with dichloromethane when you
        are finished.

   2) UV-vis Spectrum. Turn on the UV-vis instrument and allow the lamps to warm up for
      20 minutes. To prepare your sample, dissolve < 1 mg of your polymer in 3 mL of
      dichloromethane. Be sure not to make your sample too concentrated! Take a UV-vis
      spectrum of your polymer in a quartz cuvette, using plain dichloromethane as a
      blank.12 Print out a copy of your spectrum for your report.
        1
   3)    H NMR Spectrum. In an NMR tube, dissolve 10-15 mg of your polymer in 0.75 mL
        CD2Cl2. Shake the tube vigorously to mix. Obtain a proton NMR spectrum. When
        working up your data, be sure to reference your spectrum to residual CHDCl2 in your
        solvent (δ 5.32 ppm). Please integrate your spectrum, counting the region from 5.4-
        7.0 ppm as one integral (these are your alkene hydrogens) and the region from 3.8-4.5
        ppm as the second integral (these are your CH2OTBS hydrogens) (11).13 You will use
        the ratio of these regions to calculate the average number of double bonds present in
        each polymer chain and, from this, your percent yield.14 Print a copy of your
        spectrum for your report.



Notes to the Instructor

   1. Polyacetylene is somewhat light-sensitive—care must be taken to minimize exposure.
   2. For Experiment 1, it is important not to let the reaction proceed beyond 20-25
      minutes. The olefin metathesis catalyst can readily react with polyacetylene to
      extrude benzene. This leads to polymer cracking on the plate, making it fragile and
      difficult to manipulate (7).
   3. The same syringe used for Experiment 1 can be used in Experiment 2.
   4. The number of alkene units will begin to diminish if the reaction is heated too long.
      In addition, students may not see any cis alkenes in the IR due to product
      isomerization. To accommodate student scheduling, the instructor can remove the
      reactions from the heat after 12-18 h, and students can work up the reactions at a later
      time. For example, students in the test groups set up the reaction at 3pm. The
      following morning at 9am, they were removed from the heat and allowed to cool to
      room temperature. Students then returned at 1:15pm to precipitate the reaction in
      methanol.
   5. The polymer is sufficiently air-stable that it can be removed from the glove bag for
      short periods of time. Long-term storage of the plates, if desired, must be in the dark
      under an inert atmosphere.
   6. If the polymer cracks and slides off the plate, students can reattach it to the slide
      using double-sided tape and still obtain favorable experimental results.
   7. Approximately 6 g of iodine should be used per 250 cm3 of doping container volume.



                                                                                             S9
        8. Upon doping, the polymer becomes very light and air-sensitive. Exposure to air or
            bright light will lead to rapid decomposition. When this occurs, the shiny metallic
            color of the polymer will diminish, and the color will dull and blacken.
        9. On average, students obtained resistance measurements between 0.5-2 kΩ. Best
            results were obtained by placing the two points of the probe relatively close to each
            other in one of the shinier regions of the polymer. Doped polymers handled without
            the rigorous exclusion of air will typically afford measurements in the MΩ region.
            When conducted in a classroom setting of 5 groups, all students were able to acquire
            successful (non-infinite) resistance measurements.
        10. Polymer analysis can be conducted same-day after a brief period of drying en vacuo.
        11. Representative IR spectrum:




            Note: In some instances, the cis C-H out-of-plane vibrational mode was not visible in
            the IR spectrum.
        12. A polyene of 10-20 double bonds typically has four distinct transitions between 355-
            450 nm.‡ In all cases, this fine detail was not seen, and a λmax of ~450 nm was
            observed. A UV-vis spectrum of a telechelic polymer of 15 alkene units is shown:

                                                                                 Polymer: naverage = 15 alkene units




                                                                                 λmax = 452 nm




‡
    See: (a) Scherman, O. A.; Rutenberg, I. M.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 8515-8522; (b) Knoll, K.; Schrock, R. R. J. Am. Chem.
        Soc. 1989, 111, 7989-8004.



                                                                                                                                          S10
   13. Integrated 1H-NMR (300 MHz, CD2Cl2, 20 °C) spectrum of telechelic polymer:




   14. Students (n = 5 groups) obtained yields between 20-30%. The number of double
       bonds per polymer chain varied between 8 and 20.


Literature Cited

   1.  Roncali, J. Chem. Rev. 1992, 92, 711.
   2.  Ito, T.; Shirakawa, H.; Ikeda, S. J. Polym. Sci. Chem. Ed. 1974, 12, 11.
   3.  Chiang, C. K.; Druy, M. A.; Gau, S. C.; Heeger, A. J.; Louis, E. J.; MacDiarmid, A. G.; Park, Y. W.;
       Shirakawa, H. J. Am. Chem. Soc. 1978, 100, 1013-15.
   4. Klavetter, F. L.; Grubbs, R. H. J. Am. Chem. Soc. 1988, 110, 7807-7813.
   5. Jozefiak, T. H.; Ginsburg, E. J.; Gorman, C. B.; Grubbs, R. H.; Lewis, N. S. J. Am. Chem. Soc. 1993,
       115, 4705-4713.
   6. Schleyer, P. v. R.; Williams, J. E.; Blanchard, K. R. J. Am. Chem. Soc. 1970, 92, 2377-2386.
   7. Scherman, O. A.; Grubbs, R. H. Synth. Met. 2001, 124, 431-434.
   8. Chain transfer is the process by which a growing polymer chain is transferred to another molecule in a
       polymerization reaction. Chain transfer reactions reduce the average molecular weight of the final
       polymer. The molecule used to effect a chain transfer is known as a chain transfer agent. For more
       information on chain transfer, see: Flory, P. J. Principles of Polymer Chemistry, Cornell University
       Press: Ithaca, NY, 1953, 136.
   9. Telechelic polymers are low molecular weight polymers that contain terminal functional groups (e.g.
       OTBS). For more information, see: Nuyken, O.; Pask, S. Encycl. Polym. Sci. Eng. 1989, 16, 494-532.
   10. Shibahara, S.; Yamane, M.; Ishikawa, K.; Tazezoe, H. Macromolecules 1998, 31, 3756-3758.
   11. Scherman, O. A.; Rutenberg, I. M.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 8515-8522.




                                                                                                       S11
               Ring-Opening Metathesis Polymerization (ROMP):
       Preparation of Polyacetylene from 1,3,5,7-Cyclooctatetraene (COT)
                          Summary Report Information

Please include the following in your write-up:
    An introductory section including the purpose of this experiment
    Analysis of your 1H NMR data:
         Analyze the ratio of alkene to methylene hydrogens.
         From the above data, calculate the average number of double bonds in your
            polymer chain. Hint: considering that this is a telechelic polymer, what is the
              number of methylene hydrogens that must be present in your polymer? Compare this
              number with the number of hydrogens per alkene unit. It helps to consider the
              simplest scenario: a “polymer” with 1 alkene unit capped with two CH2OTBS groups.
             Once you have an average number of double bonds per polymer chain, you
              can calculate its molecular weight (g/mol). Use this estimate of MW to
              calculate your percent yield of polymer. In calculating your polymer MW, it is
              helpful if you draw it on Chemdraw. If you then select it and click on the “show
              analysis window” under the “View” tab of the menu bar, the molecular weight will be
              calculated for you. Be sure to take into account how many molecules of COT went
              into each polymer when performing your yield calculation. ☺
             Attach your spectrum to your report
    Analysis of your IR data:
         What IR stretches were the most indicative of your polymer composition?
            What conclusions can you draw regarding the ratio of Z/E alkenes in your
            polymer, assuming in this case that factors influencing intensity are the same?
         Attach your spectrum to your report

    Analysis of your UV-vis data:
         Is any fine structure seen in your UV-vis spectrum?
         If not, what was the λmax of your polymer?
         In your organic textbook, please look up the typical wavelength (λ) for a π to
            π* transition in an unconjugated alkene. Compare this with your UV-vis data.
            What conclusions can you draw from this, particularly in regard to the energy
            required to effect a π to π* transition in your polymer?

    Please cite any resistance measurements obtained from your doped COT polymer
     from Experiment 1, if any.
    Please provide a conclusion section where you reflect upon your data. Cite any
     sources of experimental error.
    Attach the carbon copies of your notebook pages. Be sure that they include a detailed
     experimental procedure and all appropriate observations.




                                                                                            S12
Pre-Lab for Metathesis Experiment
*Utilize the references from your prelab reading in answering the following questions.
1. (a) In this experiment, you will be performing a ring-opening metathesis polymerization
   to form polyacetylene. To do this, you will be using Grubbs’ 2nd generation catalyst.
   Please cite two reasons why this catalyst is preferable to early-metal systems (such as
   tungsten-based catalysts) for this reaction.

!




                    nd
          Grubbs 2
       Generation Catalyst




    (b) Why is Grubbs’ 2nd generation catalyst more reactive than his first generation
        catalyst?




2. Using [Ru]=CHCH2OTBS to represent your propagating catalyst, draw an arrow-pushing
   mechanism to depict the reaction of a single molecule of COT with catalyst to initiate the
   growth of your polymer chain.




                                                                                         S13
3. Polyacetylene films can be regarded as insulators. However, they can be modified to
   generate highly conductive materials. What chemical will you use to modify your
   polymer to improve its conductivity? How does this improve conductivity?




4. (a) Briefly rationalize why your polymer will contain a mixture of cis and trans isomers
   when all the alkenes that you are introducing into your reaction are cis.




   (b) What happens to metathesis-derived polyacetylene if it is left out at room temperature
       for a week? Why?




5. Why are low yields frequently obtained from the ring-opening metathesis polymerization
   of COT? What is the principle organic byproduct of this reaction?




                                                                                         S14
                       Pre-Lab for Metathesis Experiment
*Utilize the references from your prelab reading in answering the following questions.

1. a.    In this experiment, you will be performing a ring-opening metathesis
         polymerization to form polyacetylene. To do this, you will be using Grubbs’ 2nd
         generation catalyst. Please cite two reasons why this catalyst is preferable to early-
         metal systems (such as tungsten-based catalysts) for this reaction.




    !                             Tungsten-based systems are both air and moisture
                                  sensitive and must be handled in an inert atmosphere
                                  glovebox. In addition, the incorporation of functional groups
                                  is not well tolerated by early metal catalysts, like tungsten,
                                  limiting the diversity of molecular structure.


    b. Why is Grubbs’ 2nd generation catalyst more reactive than his first generation
       catalyst?
                                                     nd
In comparison to the first-generation catalyst, the 2 generation catalyst has a strongly σ-
donating N-heterocyclic carbene in place of one of the phosphines. This leads to a greater
reactivity of ruthenium towards π-acidic olefins.



2. Using [Ru]=CHCH2OTBS to represent your propagating catalyst, draw an arrow-pushing
   mechanism to depict the reaction of a single molecule of COT with catalyst to initiate the
   growth of your polymer chain.




!




                                                                                              S15
3. Polyacetylene films can be regarded as insulators. However, they can be modified to
   generate highly conductive materials. What chemical will you use to modify your
   polymer to improve its conductivity? How does this improve conductivity?
Iodine can be used as a doping agent. Iodine is an oxidative dopant—one π electron is
removed from the conjugated chain. The resulting unpaired electron facilitates electron
movement down the length of a polymer chain, thereby improving conductivity.



4   a. Briefly rationalize why your polymer will contain a mixture of cis and trans isomers
       when all the alkenes that you are introducing into your reaction are cis.
Olefin metathesis is a thermodynamically-controlled reaction, in that it is reversible in many
instances. The ruthenium catalyst has the capacity to come back and “back-bite” into your
product olefins, thereby isomerizing them. As trans olefins are more thermodynamically
favored than cis, some trans olefins will begin to result even though all the starting material
was cis.


    b. What happens to metathesis-derived polyacetylene if it is left out at room temperature
       for a week? Why?

If left out for a week, all of the polymer will isomerize to the trans form. Even though the
polymer will be somewhat purified of the catalyst during the methanol precipitation, a tiny
amount remaining will continue to isomerize your product to the thermodynamically preferred
trans form.




5. Why are low yields frequently obtained from the ring-opening metathesis polymerization
   of COT? What is the principle organic byproduct of this reaction?
In some instances, the catalyst can back-bite onto itself, extruding benzene. The favorability
of benzene formation, with its aromatic stabilization, can potentially rationalize the low yields
obtained from the ROMP of COT.




                                                                                              S16
18                    Molecular Modeling

18.1 Introduction
        18.1.1 Building molecules
        18.1.2 Visualizing and manipulating structures

18.2 Using Molecular Mechanics Calculations to Analyze Conformations of Hydrocarbons
      18.2.1 Butane
      18.2.2 Substituted cyclohexanes

18.3 Using MO Calculations to Understand Electron Distribution within Molecules
      18.3.1 Formal charges and charge distribution
      18.3.2 MO’s for hydrocarbons
      18.3.3 Lewis structures and VSEPR models compared with MO Theory

18.4 SN2 Reactivity

18.5 EAS Reactivity – Predicting Regiochemistry of Reactions
      18.5.1 Predictions based on partial charges in aromatic starting materials
      18.5.2 Predictions based on energies of arenium ion intermediates

18.6 Diels-Alder Reactions
      18.6.1. Rationalization of relative reaction rates based on HOMO-LUMO gap
      18.6.2. Prediction of stereochemistry based on transition state energies




                                              143
18.1 Introduction

Molecular Modeling is a general term that can refer to a wide range of activities, from
constructing “ball and stick” models of molecules to doing sophisticated computational modeling
carried out on computers. Computational modeling has been developed into a set of extremely
powerful tools that can accurately predict detailed molecular structures and calculate relative
energies of compounds. Computational modeling generally falls into two categories: 1)
molecular mechanics (MM) models that are based on force field calculations, and 2) quantum
chemical models that are based on approximating solutions to the Schrödinger equation.

Molecular mechanics models specify best distance, angle, and dihedral angle prescriptions for
various types of atoms and bonding situations, and employ simple formulae for how the energy
increases when structural requirements alter these parameters. MM calculations are extremely
fast and can be done on almost any sized molecule.

Quantum chemical models provide what are commonly called molecular orbital (MO)
calculations. They vary widely in their degree of sophistication and computer memory/time
required. MO calculations are far more general than MM calculations, which fail (often
miserably) when structures are calculated that lie outside the range for which the force field
parameters apply. The enormous advancement in speed and memory capacity of desktop
computers, combined with innovations in molecular modeling software, have made MO
calculations a practical everyday modeling tool for use in predicting detailed structures of
compounds (including lowest energy conformations), predicting the most likely products of
reactions, and rationalizing reactions and mechanisms. The calculations are not limited to
“stable” molecules; they can also be used to calculate the structures and energies of reactive
intermediates and even transition states.

The level of MO theory used by Spartan ST, the computer program employed in these exercises,
is sufficient to address many kinds of structure, bonding, and reactivity questions to a useful
degree of accuracy, however, it should be kept in mind that these models are still just
approximations of the true molecule and will not be completely accurate or correct in all cases.
There are higher levels of theory and more sophisticated programs available to computational
chemists who work in this field and need higher levels of accuracy.

General methods for using the model kit to build and visualize structures

18.1.1 Building molecules

Upon opening Spartan ST®, a window with the words and icons shown below appears.
                                                                        “blue bar”
                                                                        commands (black)
                                                                        icons “in quotes”




                                               144
   1. Click on File New, and the “model kit” panel shown
      at right will appear at the right of the window.

   2. Click on File Save As, name it [type in a file name]
      and save the file.

   3. To add an atom or a fragment. With the Organic tab
      selected as shown at right, you can add individual
      atoms by clicking on one of the 20 choices on the
      array below the window. (For example, the C(sp3) has
      been selected in the panel shown at right.) One may
      also select pre-drawn Groups or Rings (below the
      array) to add, by picking one from the list that appears
      upon clicking on the ▼ symbol to the right of each.
      Whatever is displayed in the window panel at the top
      will be added when you click on the drawing screen.
      To make butane, you only need the C(sp3). When
      you click once, the C appears on the screen with four
      yellow free valences coming off tetrahedrally.

   4. To connect to another atom or fragment. Click at the
      end of a free valence to add whatever is shown in the
      window onto the structure that you are drawing.

   5. If you make a mistake you can either undo it if you
      click on Edit Undo (or control-z) before you do anything else, or erase desired atoms or
      valences clicking the “” on the menu bar and then clicking the atom to be erased.
      (careful! This eraser stays on until you click the “+” to turn it off!).

   Note: You can only add to your structure when yellow free valences are on the screen;
   pressing most icons “finishes” your drawing: the bonds turn silver, and white
   hydrogens appear on all of the free valences. To get back in drawing mode, click on
   “+” on the menu bar. For closely related calculations it is useful to keep related
   structures in the same file.

   6. Clicking on the “E” icon does a quick molecular mechanics optimization of whatever
      structure is on the screen. This can be very useful to “shape up” structures while you are
      building them.

18.1.2 Visualizing and manipulating structures

   1. To rotate a structure, hold down the left mouse button and move the cursor in whichever
      direction you want.

   2. To move a structure, hold down the right mouse button and move the cursor.



                                              145
   3. When in structure-building mode (i.e. when the model kit is open, rotation about single
      bonds can be done by first clicking on the bond, then, while holding down the Alt key
      and the left mouse button, moving the cursor.


18.2 Using Molecular Mechanics Calculations to Analyze Conformations of
     Hydrocarbons

As an introduction to using the Spartan ST® modeling program, you will first calculate some
structures that relate to conformations. Conformations of hydrocarbons are obtained more
accurately using molecular mechanics than all but the highest level of MO calculations. The
MM programs have been specially parameterized to generate correct results for hydrocarbons.
In the exercises that follow, we will first use MM calculations to analyze conformations of some
simple hydrocarbons and then in the subsequent exercises we will move to semi-empirical MO
calculations to evaluate the electronic structure and energies of more complex molecules, using
the data to make predictions of reactivity.

18.2.1 Butane
(Do this as an individual exercise, and discuss it with your partner.)

Procedure

   1. Use the model kit to build anti butane. (see structure figures on page 147)
      .

   2. Click on File and New Molecule to get a blank screen (the anti butane structure is still in
      the file). Build gauche butane on the new blank screen.

Note: You can toggle back and forth between the two butane conformers by using the
buttons at the lower left of the screen.

   3. Do MM calculations on anti and gauche butane using Setup Calculations. Select
      Equilibrium Geometry and Molecular Mechanics using the ▼ symbols, and finally,
      click on Submit. Both molecules will be calculated (all molecules in a file are calculated
      (or recalculated) upon clicking “submit” (which is a reason not to have very many in the
      same file unless you need to directly compare them).

   4. View the results of your energy calculations by clicking on Display Spreadsheet. On the
      spreadsheet table, click at the top of the 2nd column, then click the Add... button, and add
      E, selecting kJ/mol as the units. Click on the third column and add rel. E, again making
      sure kJ/mol is selected as the units.

Note: Throughout all of the modeling exercises, use kJ/mole as the energy units and record
all calculated energy values in your lab notebook. You can obtain geometrical information
on your optimized structures as follows: Bond distances will appear at the bottom of the
screen when you click on a bond or when you click “〈?〉” followed by clicking the atoms at


                                              146
either end of the bond. Similarly, bond angles and dihedral angles can be displayed by
clicking “∠?” or “\?\” and the appropriate atoms. For each of these functions, after
clicking on 2 (or a bond), 3, or 4 atoms (in order), the current value appears in the box.
Any of the values can be changed by typing a new value in the display box.

   5. Add one more molecule to your butane file by again clicking on File New Molecule.
      This time build the highest energy eclipsed conformation of butane (the conformation
      with the methyl groups eclipsed). For the calculation to run successfully on this highest
      energy conformation, you must have the structure perfectly eclipsed and symmetrical. To
      do this, start with ethane and set the H-C-C-H dihedral angle to zero, then add two more
      methyls so they are eclipsed. Resubmit the calculation (for all three molecules in your
      file) by clicking Setup Calculations, making sure Equilibrium Geometry and
      Molecular Mechanics are selected and finally, click on Submit.

Two important things to know about Spartan ST are that it will not lower the symmetry of the
structure you enter, even if the energy would be lower, and it will only optimize your structure
by continuously lowering the energy. The program will not take your structure over even small
activation barriers in arriving at the optimized structure.
When the structure being calculated is not “locked” in a high symmetry state, the program is
designed to “crawl downhill” from the starting point until the energy stops changing.




Questions

   1. Taking the calculated energy of anti butane as the zero reference, compare the relative
      energies of anti, gauche, and eclipsed butane. How well do these agree with the
      reference values given on page 158 in Solomons 8th ed? (p. 153 in 7th ed.)

   2. From your calculations on butane conformers, can you see any advantage to the
      constraint that the program does not overcome energy barriers in optimizing your
      structure?

   3. Can you see any advantage to the constraint the Spartan ST will not lower the symmetry
      of a perfectly symmetrical structure (like eclipsed butane)?

   Note: Throughout these exercises, the files for all molecules on the screen need to be
   closed before starting on the next exercise.




                                              147
18.2.2 Substituted cyclohexanes
(Do this as a shared exercise with your partner.)

Procedure

   1. Start a new file and build equatorial methylcyclohexane. The cyclohexane molecule can
      be selected, preformed, from the model kit using the Rings ▼ menu. Add a methyl
      group to one of the equatorial positions and save the file with an appropriate file name for
      retrieval later.

   2. Click on File, New Molecule and build axial methylcyclohexane as a second molecule in
      the same file.

   3. Using molecular mechanics, calculate the equilibrium geometries and energies of the two
      molecules. Record the energy values and relative energy (energy difference) in your lab
      notebook.

   4. In a separate file, build axial and equatorial tert-butylcyclohexane and calculate their
      energies.

   5. In another separate file, build the three possible stereoisomers of 1,3-
      dimethylcyclohexane and calculate their equilibrium geometries and energies.

Questions

    1. Compare the energy differences you obtained between equatorial and axial isomers of
       methylcylohexane and t-butylcyclohexane. How well do these energy differences agree
       with the reference values given on page 169-170 of Solomons?
       (p. 161-163 in 7th ed.)

    2. List the stereoisomers of 1,3-dimethylcyclohexane in order of increasing energy based
       on the energy values you calculated.

18.3 Using MO Calculations to Understand Electron Distribution within
     Molecules

18.3.1 Formal charges and charge distribution
(Do this as an individual exercise and discuss it with your partner.)

You have been taught to write formal charges on Lewis structures, for example, the central
atoms of NH4+ and H3O+ have a +1 charge. Formal charges are useful in keeping track of
bonding and non-bonding electrons and predicting/remembering how nucleophiles and
electrophiles behave, but they are basically just a (very powerful) bookkeeping trick. The formal
charges have little to do with the actual distribution of electrons in molecules. They are what the
charge would have been if all the bonds were homopolar (that is, if the electrons in bonds


                                               148
between two atoms on the average were exactly half-way between them). But the
electronegativities of atoms vary widely, causing the actual partial charges on atoms to be quite
different from that implied by the formal charge. After calculating an optimized molecular
structure for any molecule using Spartan ST, “atomic charges” can be displayed for each atom by
clicking Display Properties followed by clicking on the atom. Unlike formal charges, these
partial charges are supposed to represent the actual charge on each atom and they can be very
useful in predicting reactivity.

Procedure

    1. Start a new file and build the molecule anisole. (Note: anisole is methoxybenzene.)
       Start with the preformed benzene ring from the model kit.

    2. Run a MO calculation on anisole and record the energy value in your lab notebook. (Go
       to Setup Calculations, select Equilibrium Geometry and Semi-Empirical using the ▼
       symbols, and click on Submit.) Look at the partial charges on the oxygen atom and
       each of the carbon atoms. Sketch the molecule in your lab notebook and label the atoms
       with their partial charges.

Questions

    1. Based on the partial charges you found for the ring carbons of anisole, which positions
       do you predict are most susceptible to electrophilic attack?

    2. Looking at the optimized structure for anisole, why does the methoxy group adopt the
       indicated conformation which places the methyl group in the plane of the benzene ring?
       This conformation is more sterically hindered than if the methyl group rotated out of the
       plane of the ring. What is the C-O-C bond angle? In valence bond terms, what is the
       hybridization of the oxygen atom?

Visualizing the electronic charge distribution of a molecule
From MO calculations, Spartan ST® can give a pictorial depiction of electronic charge
distribution in the molecule.

   1. For the anisole molecule, select Setup Surfaces (or Display Surfaces; they open the
      same window) click add... and the ▼ Surface =density, Property=potential, then go to
      the Set-up menu on the menu bar and click Submit to generate a colored ‘electrostatic
      potential map’.
   2. View the potential map by clicking Display Surfaces and checking the box next to
      density. The picture uses color coding to indicate the charge at all points on the outer
      surface (Van der Waals surface) of the electron cloud of the molecule. Red indicates
      negative charge, blue indicates positive charge, and yellow and green are near neutral.

These types of pictures have become very popular to depict molecules in textbooks. Instead of
using these pictures, we will focus mainly on other information from the MO calculation such as




                                              149
structural geometries, energy values, partial charges calculated for each atom and individual
molecular orbitals.

18.3.2 MOs for hydrocarbons
(Do this as an individual exercise and discuss it with your partner.)

Lewis structures of molecules show pairs of valence electrons as lines that represent single bonds
(one line for 2 electrons) double bonds (two lines for 4 electrons) or triple bonds (three lines for
six electrons). They are very simple, and their simplicity is sufficient for many purposes.
Combined with the natural idea that electrons in bonds repel each other (VSEPR) Lewis
structures provide a simple rationale for the fundamental geometrical features of alkanes (nearly
tetrahedral arrangement of atoms about saturated carbons), alkenes (four atoms in a plane about
each C=C) and alkynes (two atoms attached linearly to C≡C). However, these pictures and the
VSEPR rationale have little to do with modern theory of what leads to these geometrical features.
According to MO theory, the electrons are in molecular orbitals that frequently extend over the
entire molecule, and have shapes determined by the symmetry of the molecule. The MO picture
of bonding in molecules is much different that the localized bonding picture we get from Lewis
structures. One issue in successfully using simple bonding pictures, is knowing to which
situations they usefully apply. Lewis structures are certainly a useful way to consider the
structures of even complex molecules in a way that can be easily understood and from which
many good predictions of chemical behavior may be made. However, MO pictures, while more
difficult to interpret in a simple way, provide a much more accurate and realistic depiction of
molecules and lead to correct answers in many cases where Lewis bonding descriptions are
misleading.

Spartan ST® allows you to easily generate pictures of the individual MOs for molecules. They
represent portions of the spatial distribution of electron density (which is the square of the wave
function) with the lobes colored to indicate the sign of the wavefunction.

In MO theory there is generally one bonding and one antibonding MO for each pair of valence
electrons except for nonbonding valence electron pairs such as the “lone pairs” on heteroatoms
that are not involved in bonding at all. Only the bonding and nonbonding MOs of most stable
molecules are actually populated by electrons and it is only these populated MOs that can be
calculated with a high degree of accuracy. There is significantly greater uncertainty in the
calculated energies and shapes of the unpopulated antibonding MOs.


Procedure

   1. Start a new file and select the benzene ring from the Rings ▼ menu of the model kit.

   2. Do a semi-empirical calculation on benzene and record the energy value in your lab
      notebook.

   3. Select Setup Surfaces, click add... and the ▼ by Surfaces; select HOMO (or HOMO-n
      (then set n), LUMO, or LUMO+n) and OK to add a surface. Recall that these acronyms



                                                150
       stand for for “Highest Occupied MO” and “Lowest Unoccupied MO. HOMO-n (n =
       1,2,3…) allows you to view each of the filled orbitals below the HOMO in order of
       decreasing energy level. Add the HOMO and the next four filled MO’s (i.e. HOMO – 1,
       HOMO – 2, HOMO -3, HOMO - 4) and then go to the Set-up menu and click Submit to
       do the calculation.

   4. View these MOs one at a time by checking the box for each one in the Surfaces window.
      Remember to turn one off before turning another on, or you get their sum which is only
      confusing. The designations of σ and π, used with valence bonds, are also used similarly
      to designate the symmetry of MOs. For aromatic rings, the π MOs are those formed by
      mixing various combinations of the carbon p-orbitals that are perpendicular to the ring.
      These MOs all have a nodal plane (plane with zero electron density) in the plane of the
      ring. For benzene, there are three bonding and three antibonding π MOs. Examine each
      of the filled MOs you generated and classify each one as having σ or π symmetry. Also
      note the total number of nodes in each MO.


Questions

   1. What are the HOMO – n designations of the three filled π MOs in benzene?

   2. Make a rough sketch of the three filled π MOs of benzene showing where the nodes are.
      What is the relationship between the number of nodes and the energy of the MO?


18.3.3 Lewis structures and VSEPR models compared with MO Theory
(Do this as an individual exercise and discuss it with your partner.)

Most of the bonding interpretations in introductory organic chemistry use Lewis structures. The
Valence Shell Electron Pair Repulsion (VSEPR) model is often used to rationalize molecular
geometries and combined with the hybridization concepts of Valence Bond Theory to create a
simple localized bonding description. Unfortunately, these bonding descriptions are
oversimplifications that are incompatible with the MO picture of bonding and foster some
misconceptions. Electrons certainly repel each other, but the idea that what we call “lone pairs”
on disubstituted oxygen occur in two equivalent sp3 orbitals (projecting out from the oxygen like
rabbit ears) is certainly neither useful nor correct. Molecules assume equilibrium geometries that
minimize their energy. The three atoms of H2O must be linear or lie in a plane. If they were
linear only two of the oxygen valence orbitals (one s and one p) could be involved in bonding to
the hydrogens. By bending at O, three of the oxygen valence orbitals can participate in bonding
to the hydrogens, which lowers the energy of the molecule by mixing more p character into the
OH bonding orbitals. The last orbital on oxygen is the p-orbital perpendicular to the plane of the
atoms. This orbital contains a pair of electrons and cannot mix at all with the s-orbitals on the
hydrogens so the lone pair in this orbital is the only pair of electrons on oxygen that is strictly
non-bonding.




                                               151
Procedure

   1. Start a new file and click on the Inorganic menu.
      Create a water molecule by selecting the oxygen
      atom from the model kit and clicking the button
      below the periodic table that shows two bonds
      coming off of a central atom with a bent geometry
      (as shown in the figure at right). As with carbon,
      you do not need to add the hydrogens onto the
      oxygen; the program will do it for you.

   2. Calculate the Equilibrium Geometry and energy
      of the water molecule using Semi-Empirical.
      After running the calculation go to Display
      Spreadsheet and find the energy in kJ/mole.
      Record the energy in your lab notebook. Click
      Display Properties and click each atom to view
      its partial charge. Record the charges in your lab
      notebook.

   3. Select Setup Surfaces, add HOMO, HOMO-1,
      HOMO-2, and HOMO-3, then go to the Set-up
      and click submit to calculate allof the filled MO’s
      for the water molecule.



Questions

   1. Which MO contains the one lone pair on oxygen that is strictly non-bonding?
      (Hint: Which MO is entirely localized on the oxygen atom?)

   2. Do you find MOs that support the view (shown on page 39 of Solomons 8th ed.) that the
      oxygen in water has two identical lone pairs of electrons in sp3 orbitals? Explain.




                                              152
18.4 SN2 Reactivity

Predicting SN2 reactivity by calculating transition states for RCl + Cl-
(Do this as a shared exercise with your partner.)

In this exercise you will consider the reactivity of alkyl chlorides towards SN2 reactions.
Specifically, you will use MO calculations to explore the relative SN2 reactivity of the following
compounds:




The approach you will use is to calculate the energy of the SN2 transition state for the attack of
Cl- on the alkyl chloride, and subtract the energy of the starting reactants. That is to calculate the
activation energy for the following process:




In other words, you are analyzing the chloride exchange reaction for each compound. Using
chloride as the nucleophile and the leaving group allows you to take advantage of the fact that
Spartan ST will not lower symmetry making it possible to analyze the transition state. For
example, in the case of the first compound, chloroethane, the transition state of interest is the
pentavalent anion:




Procedure

(Note: for all energy calculations in this exercise, check and record both E and Eaq
values.)

   1. Choose the “5-bonded-carbon” stucture from the Inorganic drawing template. This puts
      the five valences in the desired trigonal bipyramidal geometry, three planar and 120°
      apart (the equatorial bonds), and the other two at 90° to this plane (called the axial
      bonds).



                                                153
   2. Add two chlorines to the valences that are at 180° to each other, and the appropriate
      methyl or phenyl groups to build each transition state. Run a semi-empirical
      “equilibrium geometry” on each SN2 transition state (These are actually very far from the
      true equilibrium geometry). Be sure to run the transition states as anions. Work with
      your lab partner to build and calculate each transition state. More than one of the TS
      structures can be combined in one file and the calculations run at the same time.

   3. In a separate file, build and the alkyl chloride starting molecules and calculate the
      energies of these neutral molecules using semi-empirical MO calculations.

   4. In a separate file, calculate the energy of the chloride anion by selecting the chlorine atom
      from the model kit and erasing the one valence. Use semi-empirical and be sure to run it
      as an anion.

   5. For each reaction, create a table in your lab notebook like the one below and work with
      your lab partner to run the calculations to fill in each table. (Note: The ΔE values are
      calculated by subtracting the number in the third column from the number in the third
      column from the corresponding number in the fourth column.) The Eaq calculation
      attempts to account for solvation effects and provides an estimate of how the energy of
      the molecule or ion would change if it was in an “aqueous” environment.


                       EtCl          Cl-              EtCl + Cl-      EtCl2-
                 E
                 Eaq

                    ΔE =                            ΔEaq =

   6. After calculating all of the activation energies, summarize them in a table like the one
      shown below.


                       EtCl + Cl-     iPrCl + Cl-      t-BuCl + Cl-   BzCl + Cl-
                ΔE
                ΔEaq


Discussion Points

Briefly discuss your results in terms of consistency with your expectations for these reactions.
How does solvation affect the activation energies for these reactions? How does the reactivity of
benzyl chloride compare with the various alkyl chlorides?




                                               154
18.5 EAS Reactivity – Predicting Regiochemistry of Reactions

In this exercise, you will use MO calculations in two different ways to predict the regiochemistry
of an EAS reaction. You recently carried out the nitration of methyl benzoate in lab. You
should have been able to predict the major product of the reaction using resonance arguments
based on valence bond theory. Two different types of resonance arguments are commonly used
to predict the regiochemistry of EAS reactions: arguments based on the resonance forms of the
aromatic starting materials, and arguments based on the resonance forms of the arenium ion
intermediates. Here you will carry out the corresponding MO calculations and check for
agreement with your predictions from valence bond resonance structures.


18.5.1 Predictions based on partial charges in aromatic starting materials
(Do this as an individual exercise and discuss it with your partner.)

   1. Use the model kit to build methyl benzoate. To ensure that your structure optimizes in its
      lowest energy conformation, be sure that your starting structure is the Z isomer (not the E
      isomer) as shown in the figure below. Run a semi-empirical calculation to determine the
      equilibrium geometry and energy.

   2. Check and record the partial charge at each carbon and oxygen atom in the structure.
      Generate a plot of the HOMO of methylbenzoate by selecting Setup Surfaces, Add,
      HOMO, click Submit. Note which carbons of the aromatic ring have electron density in
      the HOMO.




Questions

    1. Based on the partial charges you found for the ring carbons of methyl benzoate, which
       positions do you predict are most susceptible to electrophilic attack? Does the result
       agree with valence bond resonance arguments?



                                               155
    2. Assuming that electrophilic attack will most likely occur by attack of the electrophile on
       the electron pair in the HOMO, can you rule out certain positions on the ring as being
       susceptible to electrophilic attack?


18.5.2 Predictions based on energies of arenium ion intermediates
(Do this as a shared exercise with your partner.)

The arenium ions cannot be easily made from a benzene template, so you will need to assemble
them from individual carbon atoms.

Procedure

   1. Under the inorganic tab of the model kit, select carbon with three valences in a trigonal
      planar geometry. This provides a trivalent sp2 carbon atom. Connect five of these sp2
      carbons together placing them at 5 out of 6 positions of a benzene ring. Return to the
      model kit, click the organic tab and select a tetravalent sp3 carbon to place in the 6th
      position of the benzene ring. The final bond of the ring can be closed by selecting the
      Make bond icon from the tool menu above the field and clicking on open valences of
      each carbon to form the final bond and close the ring. (This can be a little tricky and you
      might have to try it a couple of times to get the last bond of the ring to form.)

   2. Return to the model kit, select the electrophile (NO2) from the under the Groups button
      and bond it to the one of the open valences of the sp3 carbon of the ring. Finally, add the
      carboxymethyl group onto the position ortho to the sp3 carbon. This completes the
      starting point structure for the arenium ion resulting from ortho attack of nitronium ion
      on methyl benzoate.

   3. Run a semi-empirical calculation to determine the equilibrium geometry and energy. Be
      sure to select cation before submitting the calculation. Work with your lab partner to
      similarly build and calculate the arenium ions resulting from meta and para attack by the
      nitro group. Record the calculated energies in your lab manual, and check and record the
      partial charge on each carbon of the structure.


Questions

   1. Based on your semi-empirical calculation, which of the arenium ions has the lowest,
      second lowest and highest energy? Do you notice anything surprising about any of the
      optimized structures? In this case the semi-empirical model does poorly. It is not
      parameterized very well for high energy intermediates of this type. Spartan’s highest
      level ab initio MO calculation, Hartree-Fock/6-31G* does a much better job, but it takes
      a couple of hours for each ion. These calculations have been run for you and you can
      download the results from the course website. Use the HF/6-31G* results to answer the
      following questions.




                                              156
   2. Which of the arenium ions has the lowest, second lowest and highest energy? Does the
      order agree with the semi-empirical result?

   3. Look at the partial charges on each of the carbon atoms in each molecule. (Check all of
      the carbons, not just the ring carbons.) Which carbon atoms bear the greatest amount of
      positive charge in each cation? From the partial charges do you see evidence for the
      energy differences? (Hint: positive charge build-up on two adjacent atoms is
      destabilizing. Alternation of charge is stabilizing.)

   4. What do you predict as the major mono nitration product based on the relative energies
      calculated for the arenium ions? Is this consistent with the result you obtained in lab?


18.6 Diels-Alder Reactions
Fukui was awarded the Nobel Prize in 1981 (shared with Roald Hoffmann; Woodward had died
and was no longer eligible) for developing Frontier Molecular Orbital (FMO) theory. The theory
is based on the premise that the molecular orbitals of two reactants that are closest in energy to
each other are usually the most important for considering reactivity, because the size of
electronic interactions depend upon two factors, overlap and energy difference (electronic
interactions scale with 1/ΔE, dropping to small values no matter what the overlap is when the
energy gap gets large). Simple Diels-Alder reactions are concerted cycloadditions that have a
transition state with the diene and dienophile in roughly parallel planes. In the absence of steric
effects, and for similar types of diene and dienophile structures, the principal thing that affects
reactivity is the smallest energy gap between diene HOMO and dienophile LUMO, or between
diene LUMO and dienophile HOMO. The simplest prototype Diels-Alder reaction, that between
ethylene and butadiene is sterically very favorable, but essentially does not occur. (The yield is
extremely low.) The HOMO-LUMO energy gap is too large. The reaction becomes favorable
when electron-withdrawing groups are placed on the dienophile lowering the energy of the
LUMO.

In Chem 344, we typically carry out one of the following two Diels-Alder reactions:
(The second reaction is at the top of page 158.)




2,3-dimethyl-         maleic anhydride                       1,2-diphenylcyclohexene-
1,3-butadiene                                                4,5-dicarboxylic anhydride




                                               157
Both of these reactions occur readily and give a single product in high yield.

18.6.1 Rationalization of relative reaction rates based on HOMO-LUMO gap
(Do this as a shared exercise with your partner.)

Even though it is not possible to calculate the unoccupied orbital (e.g. LUMO) energies as
accurately as the occupied (e.g. HOMO) energies, the calculated HOMO-LUMO gaps can still be
a useful guide for predicting and rationalizing reactions.

Procedure

   1. Work with your lab partner to build each of the starting molecules for each of the two
      reactions shown above and for ethylene and butadiene. Run a semi-empirical MO
      calculation on each of the molecules.

   2. After running each calculation, view the HOMO and LUMO energies by clicking Display
      Properties. These energy values are those calculated for the specific orbitals (not the
      molecule). They are typically given in units of electron volts (eV). Record the HOMO
      energies of each diene and the LUMO energies of each dienophile and calculate the
      HOMO-LUMO differences for each reaction pair.

   3. Make a table in your lab notebook summarizing the data.


Discussion Point

Briefly discuss the relative HOMO-LUMO differences for the three reactions. Are they
consistent with the fact that the reaction of ethylene with butadiene is unfavorable whereas the
other two occur readily?




                                               158
18.6.2 Prediction of stereochemistry based on transition state energies
(Do this as a shared exercise with your partner.)

Procedure
   1. Work with your lab partner to build the two possible Diels-Alder transition states (exo
      and endo) for the reaction of trans,trans-1,4-diphenylbutadiene with maleic anhydride.
      To place the two reactant molecules on the screen together first build one, then click the
      Insert button at the lower right of the screen to start building the second molecule. You
      can click on each molecule while holding down the Ctrl key to select it and separately
      move or rotate it. Place the reactant molecules in about the correct position for the endo
      and exo reactions as shown below:




               Endo                                         Exo

   2. Click the Transition button, at the right end of the menu bar above the screen, and place
      the standard electron pushing arrows as shown in the figure. To place an arrow from one
      bond to another, click on the first bond followed by the second bond. To place an arrow
      from one bond to where a new bond will be formed, click on the bond and hold down the
      shift key while clicking each of the two atoms that the new bond will join. (This is a little
      tricky. Get help from your TA if necessary.)

   3. After placing the electron pushing arrows, click the Transition button at the lower right
      of the screen to search the programs data base for this type of transition state. This should
      replace your structures with a new transition state structure with dotted lines connecting
      the two molecules where the new bonds will form. (Note: Depending on the positioning
      of the molecules, the program may fail to identify the correct endo or exo transition state.
      If this happens, the optimized transition states can be downl0oaded from the course web
      site to complete the exercise.) Once the transition state is defined, go to Setup
      Calculations, select Transition State Geometry, and run a semi-empirical calculation to
      optimize the structure and calculate the energy. Record the transition state energies for
      the exo and endo transition states in your lab notebook.

   4. Separately, work with your lab partner to build the molecules for the two possible
      stereoisomers of the product (shown at the top of page 160) the one that results from the
      endo transition state and the one that results from the exo transition state. Use semi-



                                               159
      empirical calculations to optimize these structures and calculate their energies. Record
      the energies in your lab notebook.




Questions

     1. Based on the transition state energies you calculated, which stereoisomer is formed
        faster, the one that results from the endo transition state or the one that results from the
        exo transition state?

     2. Based on the energies you calculated for the products, which stereoisomer is more
        stable?

     3. Which will be the major product if the reaction is run under kinetic control? Under
        thermodynamic control? Based on what you learned (in Chem 343) about Diels-Alder
        reactions, do you expect to get the kinetic or thermodynamic product when you run the
        reaction in lab?




                                               160
                         Chemistry 344 Molecular Modeling
                                    Spring 2007
                                   Answer Key

18.2.1 Questions

   1. Taking the calculated energy of anti butane as the zero reference, compare the relative
      energies of anti, gauche, and eclipsed butane. How well do these agree with the
      reference values given on page 158 in Solomons 8th ed? (p. 153 in 7th ed.)

       Spartan ST relative energy values for gauche and eclipsed butane (relative to anti) are
       3.3 kJ/mole and 21.80 kJ/mole respectively compared to free energy differences of 3.8
       kJ/mole and 19 kJ/mole given in Solomons. Pretty good agreement.

   2. From your calculations on butane conformers, can you see any advantage to the
      constraint that the program does not overcome energy barriers in optimizing your
      structure?

       This constraint allows calculation of higher energy staggered conformations that
       would otherwise revert to the lowest energy conformation.

   3. What are the practical advantages of the symmetry and activation barrier constraints of
      Spartan ST discussed above?

       This constraint allows calculation of certain energy maxima conformations such as
       eclipsed butane which otherwise would revert to the nearest energy minimum.


18.2.2 Questions

    1. Compare the energy differences you obtained between equatorial and axial isomers of
       methylcylohexane and t-butylcyclohexane. How well do these energy differences agree
       with the reference values given on page 169-170 of Solomons?
       (p. 161-163 in 7th ed.)

       methylcyclohexanes: 5.7 kJ/mole vs reference value of 7.6 kJ/mole.
       t-butylcyclohexanes: 26 kJ/mole vs reference value of ~21 kJ/mole.

    2. List the stereoisomers of 1,3-dimethylcyclohexane in order of increasing energy based
       on the energy values you calculated.

       cis-diequatorial < trans-axial-equatorial (+6.0 kJ/mole) < cis-diaxial (+21 kJ/mole)
18.3.1 Questions

    1. Based on the partial charges you found for the ring carbons of anisole, which positions
       do you predict are most susceptible to electrophilic attack?

       The ortho carbons have the most negative charge, followed by the para carbon. The
       ortho and para positions should be more susceptible to electrophilic attack than the
       meta positions.


    2. Looking at the optimized structure for anisole, why does the methoxy group adopt the
       indicated conformation which places the methyl group in the plane of the benzene ring?
       This conformation is more sterically hindered than if the methyl group rotated out of the
       plane of the ring. What is the C-O-C bond angle? In valence bond terms, what is the
       hybridization of the oxygen atom?

       The orientation of the methoxy group in the plane of the ring aligns the p-orbital on
       the oxygen with the π -system of the aromatic ring allowing conjugation. The C-O-C
       bond angle is 117o which is roughly consistent with sp2 hybridization.



18.3.2 Questions

   1. What are the HOMO – n designations of the three filled π MO’s in benzene?

       HOMO, HOMO – 1, HOMO – 4, are the three filled MO’s with π symmetry.

   2. Make a rough sketch of the three filled π MO’s of benzene showing where the nodes are.
      What is the relationship between the number of nodes and the energy of the MO?

       Energy increases with number of nodes. HOMO and HOMO – 1 have two nodes (one
       in addition to the normal π -node) and equal energy (-9.75 eV) whereas HOMO – 4 has
       one node (i.e. only the normal π node) and lower energy (-13.23 eV).

18.3.3 Questions

   1. Which MO contains the one lone pair on oxygen that is strictly non-bonding?

       The HOMO contains the one strictly non-bonding lone pair. This “MO” is just a non-
       interacting filled p-orbital on oxygen.

   2. Do you find MO’s that support the view (shown on page 39 of Solomons 8th ed.) that the
      oxygen in water has two identical lone pairs of electrons in sp3 orbitals? Explain.
       No. None of the other MO’s are localized on oxygen, and none of them have the shape
       or direction of sp3 hybrids.


18.4    Data Tables for SN2 Reactivity


                  EtCl                    Cl-          EtCl + Cl-        iPrCl2-
            E     -92.3                   -214.3       -306.6            -294.6
            Eaq   -95.0                   -537.5       -632.5            -530.4
            ΔE = 12.0                     ΔEaq = 102.1


                  iPrCl                   Cl-          iPrCl + Cl-       iPrCl2-
            E     -124.5                  -214.3       -338.8            -311.2
            Eaq   -126.1                  -537.5       -663.6            -545.0
            ΔE = 27.6                     ΔEaq = 118.6


                  t-BuCl                  Cl-          t-BuCl + Cl-      t-BuCl2-
            E     -158.0                  -214.3       -372.3            -324.5
            Eaq   -158.4                  -537.5       -695.9            -558.3
            ΔE = 47.8                     ΔEaq = 137.6


                  BzCl                    Cl-          BzCl + Cl-        BzCl2-
            E     47.8                    -214.3       -166.5            -156.8
            Eaq   39.4                    -537.5       -498.1            -394.2
            ΔE = 9.7                      ΔEaq = 103.9



                       EtCl + Cl-     iPrCl + Cl-    t-BuCl + Cl-    BzCl + Cl-
                ΔE     12.0           27.6           47.8            9.7
                ΔEaq   102.1          118.6          137.6           103.9


18.4 Discussion Points

Briefly discuss your results in terms of consistency with your expectations for these reactions.
How does solvation affect the activation energies for these reactions? How does the reactivity of
benzyl chloride compare with the various alkyl chlorides?

The calculated activation energies follow the expected trend for primary, secondary, and
tertiary alkyl halides where steric crowding significantly raises the energy of the transition
states in that order. Solvation has a large effect, increasing the activation energy by
stabilizing the chloride ion to a greater extent than the transition state while having little effect
on the energy of the neutral alkyl halide.



18.5.1 Questions

    1. Based on the partial charges you found for the ring carbons of methyl benzoate, which
       positions do you predict are most susceptible to electrophilic attack? Does the result
       agree with valence bond resonance arguments?

       The ipso carbon actually has the most negative charge (-.274), but among the
       unsubstituted carbons on the ring, the meta carbons have the most negative charge
       with partial charges of -0.145 and -0.166. The ortho and para carbons are close to
       neutral (-0.001, +0.040, -0.023). The charges agree with valence bond resonance
       arguments.


    2. Assuming that electrophilic attack will most likely occur by attack of the electrophile on
       the electron pair in the HOMO, can you rule out certain positions on the ring as being
       susceptible to electrophilic attack?

       If the methylbenzoate was optimized in the lowest energy conformation (the Z
       conformer with the methyl group directed away from the ring) the HOMO has a node
       through carbons 1 and 4 of the aromatic ring, so there would be no electron density at
       these carbons in the HOMO and they would not be subject to electrophilic attack.



18.5.2 Questions

   1. Based on your semi-empirical calculation, which of the arenium ions has the lowest,
      second lowest and highest energy? Do you notice anything surprising about any of the
      optimized structures? In this case the semi-empirical model does poorly. It is not
      parameterized very well for high energy intermediates of this type. Spartan’s highest
      level ab initio MO calculation, Hartree-Fock/6-31G* does a much better job, but it takes
      a couple of hours for each ion. These calculations have been run for you and you can
      download the results from the course website. Use the HF/6-31G* results to answer the
      following questions.

       Based on the semi-empirical calculations, the arenium ion from meta attack is lowest
       in energy, followed the para isomer (+6.0 kJ/mole) and the ortho isomer (+7.8
       kJ/mole). This makes intuitive sense, but is probably not correct (see Hartree-Fock
       results). The para isomer optimized by SE has the carboxymethyl group perpendicular
       to the plane of the ring which is unexpected.
   2. Which of the arenium ions has the lowest, second lowest and highest energy? Does the
      order agree with the semi-empirical result?

      The Hatree-Fock calculation shows the meta lowest in energy, followed by the ortho
      (+12.3 kJ/mole) with the para isomer highest in energy (+15.5 kJ/mole). The order of
      ortho and para is reversed compared to the sem-empirical result.

   3. Look at the partial charges on each of the carbon atoms in each molecule. Which carbon
      atoms bear the greatest amount of positive charge in each cation? From the partial
      charges do you see evidence for the energy differences? (Hint: positive charge build-up
      on two adjacent atoms is destabilizing. Alternation of charge is stabilizing.)

      The carboxyl carbon bears the highest positive charge in all three of the arenium ions.
      The second most positively charged carbon in each ion is the carbon para to where the
      nitro group added. This is typical of five-carbon conjugated cations; the highest
      charge is on the middle carbon of the five. Significantly, in the case of the para
      isomer, this places the most positively charged ring carbon next to the positively
      charged carboxyl carbon which is particularly destabilizing.



   4. What do you predict as the major mono nitration product based on the relative energies
      calculated for the arenium ions? Is this consistent with the result you obtained in lab?

      The results indicate that meta substitution should be the major product as they
      observed in lab.




18.6.1 HOMO and LUMO Energies

Reaction                HOMO of diene            LUMO of dienophile       Difference
ethylene
butadiene                      -9.58 eV                 1.23 eV                 10.81 eV
maleic anhyddride
dimethylbutdiene               -9.51 eV                 -1.55 eV                 7.96 eV
maleic anhydride
diphenylbutadiene              -8.45 eV                 -1.55 eV                 6.90 eV
18.6.1 Discussion Point

Briefly discuss the relative HOMO-LUMO differences for the three reactions. Are they
consistent with the fact that the reaction of ethylene with butadiene is very unfavorable whereas
the other two occur readily?


The two reactions with substituted dienes and maleic anhydride have a significantly smaller
energy gap between the HOMO of the diene and the LUMO of the dienophile consistent with
the fact that these reactions occur readily to give good yields of product whereas the
ethylene/butadiene reaction does not.



18.6.2 Questions

      1. Based on the transition state energies you calculated, which stereoisomer is formed
         faster, the one that results from the endo transition state or the one that results from the
         exo transition state?

          The endo transition state is slightly lower in energy (by 1.7 kJ/mole) indicating that
          the stereoisomer resulting from this transition state (the isomer with the phenyl
          groups and the anhydride ring on the same side of the cyclohexene ring, i.e. all cis)
          should form faster.

      2. Based on the energies you calculated for the products, which stereoisomer is more
         stable?

          The stereoisomer that comes from the exo transition state, with the phenyl groups
          trans to the anhydride ring is much more stable (by 42.5 kJ/mole).

      3. Which will be the major product if the reaction is run under kinetic control? Under
         thermodynamic control? Based on what you learned (in Chem 343) about Diels-Alder
         reactions, do you expect to get the kinetic or thermodynamic product when you run the
         reaction in lab?

          The less stable all cis isomer should be the major product when the reaction is run
          under kinetic control. The reaction run in lab is under kinetic control as most Diels-
          Alder reactions are.
                                     Chemistry 344
                                   Molecular Modeling
                                      Spring 2007
                                     Notes for TAs

Important user information for all calculations using Spartan ST:

          •   Whenever a calculation is submitted a window should pop up saying that the
              calculation has started. When the calculation is complete, a window will pop up
              saying that it has completed. If the first window doesn’t pop up, then the
              calculation did not initiate for some reason. At any time, the user can check if a
              calculation is in progress by clicking on the Options, Monitor at the upper right
              of the screen. The monitor window will show the elapsed time for the calculation
              that is running and any other calculations that have been queued. Queued
              calculations can be cancelled by highlighting them in the monitor window and
              clicking on Edit, Kill Selected.

          •   Every time a new calculation is submitted, one needs to check and make sure the
              right type of calculation (i.e. molecular mechanics or semi-empirical) is selected
              in the Setup, Calculations menu. The default calculation is Hartree-Fock/3-21G
              and it often gets run by accident when students forget to change it, resulting in
              long delays and confusion.

          •   Students will generally be viewing their calculated energy values by clicking
              Display Spreadsheet and adding the desired values to the spread sheet display.
              The column width of the spread sheet columns can be easily adjusted by clicking
              and dragging the border of the top cell of the column. If the column width is too
              narrow some of the left digits of the numbers may be cut off. This can be very
              confusing to students if there is a minus sign before the number that gets cut off or
              some left hand digits of the actual number get cut off. The watch-out is to make
              sure all column widths are expanded wide enough to show space to the left of the
              numbers.




18.2   Using Molecular Mechanics Calculations to Analyze Conformations of
       Hydrocarbons.

          •   Eclipsed butane must be constructed exactly as stated in procedure 5 on page 147.
              Otherwise it will likely have some asymmetry and revert to gauche butane when
              the calculation is run.
18.3   Using MO Calculations to Understand Electron Distribution Within Molecules

          •   This section is intended mainly to transition the students from molecular
              mechanics to molecular orbital calculations and introduce them to the most useful
              MO analysis tools that Spartan ST provides.

          •   Section 18.3.3 is intended to alert them up front that the spatial distribution of
              elections as determined by MO theory is often very different than what they have
              learned from overly simplified Lewis, Valence Bond, and VSEPR descriptions.
              Some students miss the point, but it is an important point (so you may need to
              help them get it). The oxygen in water (or ethers) is not sp3 hybridized and
              doesn’t have two equivalent pairs of non-bonding electrons on the oxygen.




18.4   SN2 Reactivity

          •   Students should be able to complete the exercises in Sections 18.2, 18.3 and 18.4
              during the scheduled lab time of the first day. They are responsible for
              completing any remaining uncompleted work up through Section 18.4 on their
              own time, before the second lab day. On lab day two, they should all be starting
              on Section 18.5.

          •   Important point. When they calculate the energy of chloride ion, they need to
              select a chlorine atom from the model kit, erase the one valence off of the
              chlorine and then run the semi-empirical calculation as an anion. If they leave
              the valence on chlorine it will be converted to HCl.


18.5   EAS Reactivity – Predicting Regiochemistry of Reactions.

          •   For exercise 18.5.1 on page 154, note the importance of students building
              calculating the Z conformer of methyl benzoate. If they end up with the E
              conformer, the HOMO is different and question 2 doesn’t make any sense.

          •   In Section 18.5.2, we are having the students build the various arenium ions for
              methyl benzoate nitration and run quick semi-empirical calculations, so that they
              understand the structures they are working with and how the calculation is set up,
              but we don’t want them spending a lot of time trying to analyze the results of the
              semi-empirical calculation. We want them analyzing the optimized structures
              from the Hartree-Fock calculation that they download from the course website.

          •   For Question 1 on page 156, where it asks if they notice anything surprising about
              the structures, they should not overanalyze the question. Just take a quick look at
              the semi-empirical structures and note if there is anything that doesn’t look right
              about them. The ortho and meta attack structures look fairly reasonable, but the
              para attack structure has the carboxymethyl group perpendicular to the ring which
              is not likely.

          •   For Question 3 on page 156, it is important that they look at the charge on
              every carbon atom in the structure, not just the ring carbon atoms.


18.6   Problem Set E: Diels-Alder Reactions

          •   The Diels-Alder transition state exercise in Section 18.6.2 is a little tricky to set
              up properly. Students have gotten a lot of variation in the results. They should
              know that when things work right, the endo transition state is lower in energy than
              the exo. They are supposed to know that, but you should remind them, so that
              whether or not they are able to calculate them, they have the background to
              answer the questions on page 159.

          •   Key to getting the transition state exercise to work is building the maleic
              anhydride molecule first and optimizing it’s structure (using E minimize),
              then building the 1,4-diphenyl-1,3-butadiene second and making it nice and
              planar, then positioning the two molecules for exo or endo attack and adding
              the electron pushing arrows.

          •   If they have properly constructed the endo and exo products, they should find that
              the exo product is more stable, lower energy than the endo product in contrast
              with the previously calculated transition states which show that the endo
              transition state is lower in energy.

				
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