Chemistry 345 Final Exam Study Notes

Section I: Spectroscopic Study of (cyanomethylene)cyclopropane

  • Overview: This section covers the two-step synthesis of (cyanomethylene)cyclopropane from a cyclopropane derivative, including the preparation of ylide and its reactions.

    • Ylide Generation:

    • Step 1: Generation of an ylide from a commercially available salt using aqueous sodium hydroxide.

    • Mechanism: Provide an electron-pushing mechanism for this transformation.

    • Impact of the Cyano Group:

      • Characterization of the cyano group as a π electron-withdrawing group (EWG) or a π electron-donating group (EDG).

      • Resonance Structures: Offer a set of resonance structures that justify the characterization of the cyano group.

      • Definition: A π electron-withdrawing group is a substituent that pulls electron density away from the rest of the molecule, which typically stabilizes certain electron-rich species or intermediates.

      • Examples: Analyze specific resonance structures with arrows indicating electron movement.

  • Stabilization/Destabilization of Ylide:

    • Rationalization: Discuss how the -CN group can stabilize or destabilize the ylide.

    • Indicate two distinct rationalizations, referencing orbitals mixing, charge delocalization, or bond dipoles.

    • Orbitals Mixing: Explain how hybridization affects stability.

    • Charge Delocalization: Discuss how resonance affects electron distribution.

  • Step 2: Reaction of Ylide with Hemiacetal

    • Catalysis: Reaction catalyzed by benzoic acid (10 mol% PhCOOH). Convert 1-ethoxy-1-cyclopropanol to cyclopropanone.

    • Mechanism: Provide an electron-pushing mechanism for this formation, showing all structures, lone pairs, formal charges, and bonds.

  • Stability Comparison:

    • Discuss why cyclopropanone is as stable as its hemiacetal and ethanol, even though ketones generally are more stable than their hydrates or hemiacetals.

    • Use energy metrics: 0.1 kcal/mol (cyclopropanone) vs. 0.0 kcal/mol (1-ethoxy-1-cyclopropanol).

    • Rationalization: Explain the unique circumstances that lead to cyclopropanone’s stability.

  • [2+2]-Cycloaddition Mechanism:

    • Provide an electron-pushing mechanism for the [2+2]-cycloaddition and the reverse of this reaction with cyclopropanone to create (cyanomethylene)cyclopropane.

    • Clearly label all lone pairs, radicals, formal charges, and the processes of bond-breaking/creating.

  • Energy Analysis of Isomers:

    • Compare (cyanomethylene)cyclopropane and pyridine (C5H5N).

    • Note: (cyanomethylene)cyclopropane is about 50 kcal/mol higher in energy.

    • Stabilization/Destabilization Factors: Discuss factors affecting each compound's stability.

      • Pyridine stabilizing factors: aromaticity and resonance.

      • Factors destabilizing (cyanomethylene)cyclopropane: angle strain and lack of resonance stabilization.

  • NMR Analysis:

    • Analyze the provided 1H-NMR and HSQC spectra for signal assignments.

    • Provide your assignments of signals C2, C4, and C5, and label all relevant structures.

  • 1H-NMR Signal A:

    • Discuss the specificity of the signal and draw conclusions about the molecule structure.

    • Determine the coupling constant for this signal and elaborate on how coupling patterns and integration confirm the identity of (cyanomethylene)cyclopropane.

  • IR Spectroscopy:

    • Identify spectral features that confirm the presence of (cyanomethylene)cyclopropane.

    • Label absorptions used for confirming structure.

Section II: Synthesis of 4-Fluoro-phenylalanine

  • Reaction Overview: Analyze various steps of the proposed synthesis (

    • Step 1: Ethyl acetoacetate acts as a nucleophile; discuss the acidity differences between two possible α-carbon atoms. Explain using pKa values and resonance structures.

    • Resonance Structure: Include diagrams illustrating the resonance stabilization of the more acidic α-carbon.

  • Selection of Base:

    • Discuss the importance of sodium ethoxide as a base in Step #1. Provide a mechanism highlighting a side reaction with ethoxide and an electrophilic carbon.

    • Explain why sodium ethoxide is preferred for its electrophilicity tuning.

  • Step 2 Reaction:

    • PES (Potential Energy Surface): Create a PES for the reaction between the product of Step #1 and 1-(bromomethyl)-4-fluorobenzene. Maintain mass and charge balance in your depiction.

    • Provide another example of a slower alternative reaction using a different electrophile.

  • Base Treatment of Product:

    • Discuss the mechanism following the addition of 4-fluorobenzyl bromide, in presence of sodium hydroxide. Illustrate this with a full representation.

  • Oxidation with Iodine:

    • Identify intermediate products from the oxidation of a methyl ketone with iodine and discuss the reactions of hydroxide, emphasizing why certain intermediates do not react.

  • Thermodynamic Forces:

    • Identify driving forces behind high yield reactions under specified conditions.

  • Bromination In Acidic Conditions:

    • Draw the mechanism for the bromination reaction and address differences in products created under acidic conditions.

  • Cyano Group Installation:

    • Discuss factors for nucleophile, transition state, and leaving group that increase the reaction rate of nucleophilic substitution reactions involving the cyano group.

  • Darapsky Degradation Overview:

    • Explain the mechanism converting acyl azide to isocyanate and outline the hydrolysis mechanisms leading to the final product. Illustrate the steps clearly with reaction species labeled, particularly carbamic acid's decarboxylation.

Section III: Predicting Reaction Products

  • Multiple Predictive Questions: For each reaction provided, identify major products or outline necessary reagents.

    • Emphasize each stereocenter and stereoisomer where applicable.

    • Connect reasoning behind reaction favorability using stability analysis, acyl chloride reactivity, and energy comparisons in reversible reactions.

End of Study Notes