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Presented by Matthew Shelnutt

   Intramolecular and Intermolecular         Cyclopropanation Studies using        Ethyl 2-diazo-3-oxonon-8-enoate        and Cyclohexene. Presented by Matthew Shelnutt. Research Objectives. Nature of the competition occurring inter- and intra-molecularly during a cyclopropanation.

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Presented by Matthew Shelnutt

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  1.    Intramolecular and Intermolecular         Cyclopropanation Studies using       Ethyl 2-diazo-3-oxonon-8-enoate       and Cyclohexene Presented by Matthew Shelnutt

  2. Research Objectives • Nature of the competition occurring inter- and intra-molecularly during a cyclopropanation. • Reaction utilizing rhodium (II) acetate as a catalyst and cyclohexene as an intermolecular competitor. • The length of the carbon chain varied per research student.

  3. Uses of Cyclopropanation • Cyclopropanation reactions are used in a variety of fields: • They provide “key” intermediates in the synthesis of pyrethroid insecticides such as permethrin. Permethrin is commercially available for use in pet sprays and crop dusting. • Pharmaceutically, they provide the cyclopropanes found in antifungal drugs such as ambruticin. Permethrin Structure

  4. Intended Products We hoped to end up with these products according to the following mechanisms, including the synthesis of all of the starting materials:

  5. Overall Chemical Equation to form the Dienolate Reaction Mechanism

  6. Overall Chemical Equation to form the Keto Ester Reaction Mechanism ethyl 3-oxonon-8-enoate

  7. Overall Chemical Equation to form para-Toluenesulfonyl azide Reaction Mechanism

  8. Overall Chemical Equation to form Ethyl 2-diazo-3-oxonon-8-enoate Reaction Mechanism

  9. Cyclopropanation using Ethyl 2-diazo-3-oxonon-8-enoate, Cyclohexene, and a Rhodium (II) Catalyst

  10. Laboratory Synthesis • Initial synthesis proceeded as follows: • LDA in a 200 mL round bottom flask • 0 C, Nitrogenous atmosphere • Ethyl Acetoacetate added dropwise with stirring • 5-bromopent-1-ene added dropwise to the resulting solution to form dienolate Synthesis Apparatus

  11. Laboratory Synthesis • Wash with 10% sulfuric acid • Solution extracted 3 times with ether • Ether collected and dried over BaSO4 • Now anhydrous solution placed on rotary evaporator to remove solvent. Liquid-Liquid Extraction The Product

  12. Purification • To isolate our compound from impurities, we implemented the technique of gravity column chromatography. • The solvent used was a mixture of 2 Ligroine : 1 Petroleum Ether : 1 Ethyl Acetate Column Chromatography Purification Apparatus

  13. Further Purification • The initial column showed little separation. A new column was set up, but this time with a new solvent. Possible choices were: • 3 MTBE : 1 Isopropyl alcohol • 3 Methylene Chloride : 1 Methanol • 3 Hexanes : 1 Ethanol • Toluene, with a methanol flush • Toluene with methanol flush chosen to run the column. Running TLC Plate

  14. Vacuum Distillation • Solution added to round bottom flask, and fitted with condenser tube. • Hot oil bath made with electrical current. • Heated so that impurities with lower boiling points will evaporate and condense out. Distillation Apparatus

  15. GC/MS Analysis of Products • Product retention time is 6.310. • Extremely small peak – can’t be seen • Mass Spec. data shows molecular weights of all ions detected. • Includes 198, the peak for the product. • Larger ions peaks appear to be rearrangements of the product. • The product wasn’t there in enough quantity to be used, and so the procedure was deemed unsuccessful.

  16. Laboratory Synthesis II • Creating our own starting products might have been a little too ambitious. • Using the standard Grignard reaction procedure, we decided to create an enoate compound using bromobutane and Magnesium to create Grignard reagent, and then reacting that with diethyl amine and 4-bromo-pent-1-ene to produce the desired dienoate as shown:

  17. Grignard Mechanism

  18. Grignard Mechanism CONT. Ethyl 3-oxooct-7-enoate

  19. Grignard Procedure • Typical Grignard – Magnesium chips, ether, and bromobutane are added to 500 mL round bottom flask. • Reflux started by mild heating. • Diethyl amine added in dropwise to a the resulting Grignard reagent at 0 C. • Ethyl acetoacetate added dropwise at 0 C, and stirred for 30 minutes. • Allyl bromide is added at 0 C and allowed to stir overnight to ensure reaction completion. • Rinsed with acid to dissolve remaining solid, extracted using ether, and run through the GC. Synthesis Apparatus

  20. In the future.. • In the process of attempting to synthesize a suitable dienoate for our competition reactions, we discovered how difficult it was to use chemicals such as LDA to get a meaningful yield. • To correct for this, and one of the last syntheses done, we utilized a Grignard mechanism to produce the dienoate. • We are going to continue research on the production of enoates using Grignard-like reactions to make a more “undergraduate friendly” way to produce them. • 4 or 5 other alkyl halides will be used in a similar process to ensure the same great yield and to ensure reproducibility.

  21. Recognitions • Dr. Hornbuckle, my wonderful advisor • Clayton State University • The Natural Sciences Faculty and Staff • The Department of Natural Sciences for funding our research • Dr. Furlong, Department Head • Joe Holak, partner • Hieu Dinh, partner

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