EXPERIMENT 9: Lidocaine Research Project: Outline and Research Proposal 20 Points Overview For this project students will research the drug lidocaine and design a synthesis of a lidocaine derivative. Some groups may even synthesize molecules that have never been made before or have only been made by a few other people. The pure lidocaine derivatives will be collected and submitted to biology professor Dr. Ian Hall to test for biological activity. Schedule Week 1: Learn how to use ChemDraw and SciFinder, research lidocaine and lidocaine derivatives (what is it and how is it synthesized), find a lidocaine derivative structure that your group would like to synthesize and make a proposal. Week 2: Prelab: Create reaction table(s) in your lab notebook for the two reactions in your synthesis. Have your calculations approved by your instructor before you begin. Complete the first step of your synthesis and possibly start the second step of your synthesis. Week 3: Complete 2nd step of synthesis and possibly start purification of your final product Week 4: Finish purification of your product and analyze your product using IR and NMR. Week 5: Only if necessary. Week 1 Research Proposal 1. Download ChemDraw professional on your laptop (https://sitelicense.cambridgesoft.com/sitelicense.cfm?sid=508) or use a university computer. Use ChemDraw to draw the structure of Lidocaine, select the structure and paste it into a Word document. (2 pt) 2. ChemDraw can generate IUPAC names for organic molecules. This is very helpful for complicated molecules. Double click on the lidocaine structure to select the structure. Then look under Structure, Convert Structure to Name. This will generate the IUPAC name for lidocaine. Paste this name below your lidocaine structure. (1 pt) 3. ChemDraw can calculate molecular weights for molecules. Select lidocaine and look under View, Show Analysis Window and then check the Mol. Wt. box and click paste. Copy this MW into your Word document. (1 pt) 4. ChemDraw can predict 1H and 13C NMRs. Select the lidocaine structure and then look under Structure, Predict 1H- NMR Shifts. Then copy the NMR spectrum into your Word Document. You do not need to copy the structure or the list of all of the peak numbers. (1 pt) 5. In addition to organic molecules ChemDraw has templates for complex molecules, glassware and biology images. Look under templates, which is in the side toolbar and find five interesting template images/structures. Paste these into your Word document. (1 pt) SciFinder/Research Proposal For the next part of the assignment, use SicFinder Scholar which is the “Google of chemistry”. You can search by topics and keywords. You can also search by molecular structure which is very important for organic chemistry research. You can draw the structure of a molecule and find journal articles that describe how to synthesize the molecule. Structures from ChemDraw can be directly searched from ChemDraw (select structure, Search, Search SciFinder) 6. Create a SciFinder account 7. Access SciFinder. 8. Search the scientific literature using SciFinder to discover the uses of lidocaine and how it works (its mode of action). You may also use Google/Google Scholar to find information on this topic. Answer the following questions and include references for at least two journal articles used to find the answers. What are the uses of lidocaine and how does it work? (2 pt) 9. Using SciFinder draw the structure of lidocaine using the structure editor and find a synthesis of lidocaine in a scientific journal article and cite the reference. Your synthesis should begin with chloroacetyl chloride. Draw the sequence of reactions in ChemDraw that you find in the article. Draw each reaction individually. Include all of the chemicals over the arrow in each reaction. Copy the reference for the journal article for the lidocaine synthesis into your Word document. No mechanisms need to be drawn. (2 pt) a. Login to SicFinder b. Click on Chemical Structure c. Click to Edit (in the box) d. Use the chemistry drawing tools to draw lidocaine. e. Click OK f. Click Search (you should select exact structure) For future searches you can also select substructure if you would like to see results that include more complicated structures. a. If you ever get no results from a search, go back and edit your structure until you get results g. Pick a structure from the results that is lidocaine and has a Green Flask and click on the Green Flask to see reactions to make lidocaine h. Choose Product and click Get (this will show you all of the reactions in the literature that make the molecule) 10. Search SicFinder for lidocaine analogs or derivatives. When the structure of a drug is changed the biological activity can be changed to make it better or worse. What parts of the structure of lidocaine can be easily altered to change its biological activity? Think about the molecules that were used in the lidocaine synthesis. Cite any references for lidocaine derivatives that you find. (1 pt) 11. Propose a derivative of lidocaine that you would like to synthesize that begins with chloroacetyl chloride. Draw the structure in chemdraw and include it in your Word document. Then propose a synthesis of your derivative based off of the lidocaine synthesis you found. (1 pt) 12. Search your proposed structure in SicFinder and determine if your molecule has been made. List articles that synthesize your molecule or list articles that synthesize something similar to your structure. (1 pt) 13. You may make slight changes to your structure in Scifinder and try to create a derivative of lidocaine that has never been made. 14. Select a lidocaine derivative to synthesize and get approval from your instructor. Then propose a synthesis of your unknown lidocaine derivative using reactions that you saw in the previous questions. Draw the reactions in ChemDraw. You may be able to use the reactions from your synthesis of lidocaine. (2 pt) 15. The following chemicals are available and can be used in your synthesis. If you need a chemical that is not listed you should look up the price of the chemical from Sigma Aldrich. If the chemical is expensive (more than $5 per gram) you may need to choose a different derivative. All groups will begin with chloroacetyl chloride. 16. After your synthesis is approved, list ALL of the chemicals and supplies that will you need for your synthesis. List all chemicals including reagents, solvents, glassware and chemicals used in purification and workup. You should try to make100-500mg of product. Look at the yields of similar reactions to approximate how much of each chemical you will need to start with. List the amounts of each chemical that you will need. (3 pt) 17. Then click on the chemicals from the reaction that has an orange Erlenmeyer flask with a price tag. Find the price from a chemical supplier such as Sigma Aldrich. 18. List the prices for the chemicals that you will need. You instructor will let you know which chemicals we may need to purchase. Use prices from Sigma Aldrich. (1 pt) 19. Look at the reaction times of reactions that are similar to yours and make an estimated schedule for completing your synthesis. Don’t forget to include time for purification and analysis (IR/NMR). (1 pt) 20. Print a copy of your research proposal and give it to your instructor before you leave lab.