Organic Chemistry II Lab                                 School of Science and Technology
CHEM 2211K (Fall 2012)                                   Georgia Gwinnett College

‘Introduction to the Organic II Laboratory Multi-Step Synthesis Project’

1. Objective:

Introduce the concept for the Organic Chemistry II Multi-Step Synthesis Project

2. The Organic Chemistry Laboratory Synthesis Project:

During organic I, you’ve been introduced to some of the basic principles behind organic
synthesis. Although what you have been exposed to so far covers a relatively small number of
functional groups, grasping the basic concepts of retrosynthetic analysis and putting series of
reactions together in a particular order are extremely important skills to master.

The number of new functional groups (and associated reactions) traditionally introduced in the
organic II semester makes synthesis that much more of a complicated, involved process that
requires some real critical thinking skills. Because of this much larger emphasis on synthesis in
the organic II class, it would make sense to also give the laboratory experience a considerable
synthesis focus – and that is what we have planned.

In terms of organic synthesis, arguably the most important new class of reactions you will be
introduced to in the second semester of organic chemistry are the reactions of benzene, known as
electrophilic aromatic substitution (EAS) reactions. These reactions concern themselves with the
different groups you can substitute onto a benzene ring, as well as subsequent functional group
interconversions (FGI’s) of those groups.

Aromatic rings (mainly benzene) are a common occurrence in a wide variety of over-the-counter
and prescription medications, and thus it seemed appropriate that we choose aromatic synthesis
(multi-step synthetic routes starting from benzene or simple benzene derivatives) as the focus for
our synthesis project.

The goal of this synthesis project is to expose you to the
experimental methods involved in a multi-step
synthesis of a derivative of the early antibacterial drug
sulfanilamide (the first of the so-called ‘sulfa drugs’).

But, why choose sulfa drugs? Our criteria were as follows: the target compounds had to be (a)
preparable in a reasonable number of steps, and (b) something that every student could relate to.
Sulfa drugs work in this case because they can be made in a series of approximately 5 steps from
the provided starting material, and as examples of the earliest antibacterial drugs, they are
scientifically and historically relevant. Plus, they are still in use today, and so either yourself or
one of your relatives will have taken or is currently taking sulfa drugs to fight off infection.

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Organic Chemistry II Lab                                 School of Science and Technology
CHEM 2211K (Fall 2012)                                   Georgia Gwinnett College

3. The Project and what will be required:

Rather than performing a series of individual, disconnected experiments, the experimental work
you begin at the start of this semester will have a direct effect on your results and product yield
at the end.

Each student group will consist of 2 people. Groups will be assigned at the start of the semester,
and you will work together on this project until you generate your pure sulfa drug final product
at the semester’s end.

During the semester, each group will accomplish the following tasks:

   Choose a target sulfanilamide derivative to synthesize, from an available list.

   Research a possible procedure / possible procedures for the formation of your target
    compound (library and on-line research; Inter-Library Loan capabilities, through the GGC
    library, will be available to those groups that wish to use it), based on the initial scheme
    shown below, in which the starting material is the aromatic amine, aniline.

   Once a synthesis has been finalized with the blessing of your instructor, write a clear, concise
    and accurate procedure in your lab notebook (using the setup you have become acquainted
    with during the organic I lab experiments - UTORP, overall reaction, mole table, mechanism,
    etc.) for each of the experimental steps you will be performing in your synthesis.

   Follow the procedure in your notebook (no other sources of information will be allowed in
    the lab - it is up to you to write procedures that you can easily understand and follow) to
    perform each of the steps in your synthesis, making sure that observations are clearly noted
    in your lab notebook as appropriate.

   Isolate and purify (again, according to your written procedure) each of the intermediate
    products you form in your synthetic procedure.

   Perform analysis on each of your products (% yield, TLC, IR, 1H and 13C NMR, melting
    point, GC-MS) to completely evaluate the economy of synthesis, structure and purity of the
    product from each of your reaction steps. You will also calculate an overall % yield of your
    final product, based on the amount of aniline you began with.

                                           Page 2 of 5                                10/4/12
Organic Chemistry II Lab                                 School of Science and Technology
CHEM 2211K (Fall 2012)                                   Georgia Gwinnett College

   Write a complete lab report (in a similar format to that used in the organic I laboratory)
    detailing your entire synthetic pathway from start to finish. There will be only one of these
    reports, due at the end of the semester, and so it will be a long assignment.

   Make a final, oral presentation to your peers and faculty at the end of the semester detailing
    each step of your synthesis, the problems you encountered and how you overcame them, and
    your overall success in this synthesis project.

   Report to your peers about your synthesis progress when called on by your instructor. Both
    group members need to be involved in this spontaneous oral report. These assignments will
    not be fixed, but chosen at random during the semester. Thus, your group always needs to be
    on their toes and ready to go when called upon.

4. How will the grading work for this project?

Your points total for the organic chemistry II synthesis project will be based on the following:

   The thoroughness of the research you perform and articles / sources you find relating to the
    synthesis you will be performing, as well as the on-paper synthetic procedure you design.

   The detail and accuracy in the procedures you write in your lab notebook.

   Your synthetic work in the lab during the semester (ie - how efficiently you use your lab
    notebook, how safety-conscientious you are in the lab, your degree of independence when
    working through your procedures - in other words, how much you do or do not rely on the
    instructor for help).

   The quantity and purity of each of your product samples (intermediate and final products).

   How well you communicate the progress of your synthesis to your peers when called upon
    (an oral progress report may be requested of your group more than once during the semester).

   The preparation and delivery of your final synthesis presentation at the end of the semester.

   The completeness of your spectroscopic analyses for each of your synthesis products (this
    may be graded as part of your final semester lab report).

   Your final, end-of-semester lab report detailing each step of your total synthesis.

   Important note: If, at any stage of the synthesis, you lose / destroy / throw away your
    product, in order to be able to continue with the project you will need to buy more of
    that product from your instructor. Extra product can be bought from your instructor
    at a cost of 100 points / gram of product.

                                           Page 3 of 5                                10/4/12
Organic Chemistry II Lab                                   School of Science and Technology
CHEM 2211K (Fall 2012)                                     Georgia Gwinnett College

Graded items and associated points values - Organic II Lab

      Graded Item                                                                         Points

      Articles / documents found from initial research                                     100

      Pre-labs - Written procedures in notebook (equation, mole table, UTORP, etc)         150
      Efficiency and effectiveness of lab work during the semester                         200

      Quantity and purity of each product; overall % yield for synthesis                   100

      Oral communication of synthesis progress to peers                                     50

      Final presentation at the end of the semester                                        100

      End-of-semester lab report covering the entire synthesis                             300

      Total Laboratory Points                                                             1000

5. What will the schedule for the semester’s labs look like?

   The schedule for this lab semester will be unlike that of other lab classes you have taken so
    far; rather than starting a new experiment every two weeks, you will be performing this
    project over the course of the whole semester. This means that different groups may be
    working on different steps of their synthesis during any given week of the semester. Thus,
    there will not be a concrete schedule for each and every week.

      Week 1         Synthesis Project Intro Day - Group memberships / Synthetic targets decided
      Week 2               Library / Online Research for sulfanilamide derivative synthesis
      Week 3                                       Lab work - day 1
      Week 4                                       Lab work - day 2
      Week 5                                       Lab work - day 3
      Week 6                                       Lab work - day 4
      Week 7                                       Lab work - day 5
      Week 8                                       Lab work - day 6
      Week 9                                       Lab work - day 7
      Week 10                                  Midpoint Presentations
      Week 11                                      Lab work - day 8
      Week 12                                      Lab work - day 9
      Week 13                                     Lab work - day 10
      Week 14                               THANKSGIVING HOLIDAY
      Week 15                                      Synthesis Exam
      Week 16                                 Final Group Presentations

                                             Page 4 of 5                                10/4/12
Organic Chemistry II Lab                                School of Science and Technology
CHEM 2211K (Fall 2012)                                  Georgia Gwinnett College

6. Sulfa drug targets for synthesis project

You will choose one of the following sulfa drugs as your final product for this project:

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