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11.2: The Discovery of Nucleophilic Substitution Reactions

  • Page ID
    31514
  • Objectives

    After completing this section, you should be able to

    1. write an equation to represent the Walden inversion.
    2. write a short paragraph describing the Walden inversion.
    3. describe, using equations, a series of reactions interconverting two enantiomers of 1-phenyl-2-propanol which led to the conclusion that nucleophilic substitution of primary and secondary alkyl halides proceeds with inversion of configuration.
    Study Notes

    The IUPAC name for malic acid is 2-hydroxybutanedioic acid. This acid is produced by apples, a fact which seems to have been appreciated by the British novelist Thomas Hardy in The Woodlanders:

    Up, upward they crept, a stray beam of the sun alighting every now and then like a star on the blades of the pomace-shovels, which had been converted to steel mirrors by the action of the malic acid.

    In 1896, the German chemist Paul Walden discovered that he could interconvert pure enantiomeric (+) and (-) malic acids through a series of reactions. This conversion meant that there was some kind of change in the stereo chemistry made during the reaction.

    (-)-Malic acid reacts with ether and PCl5 to produces (+)-Chlorosuccinic acid. (+)-Chlorosuccinic acid reacts with Ag2O and water to produce (+)-Malic acid. (+)-Malic acid reacts with ether and PCl5 to produce (-)-Chlorosuccinic acid.

    These reactions are currently referred to as nucleophilic substitution reactions because each step involves the substitution of one nucleophile by another. These are among the most common and versatile reaction types in organic chemistry.

    Example of a nucleophilic substitution reaction where the nucleophile replaces a different nucleophile.

    Further investigations into these reaction were undertaken during the 1920's and 1930's to clarify the mechanism and clarify how the inversion of configurations occur. These reactions involved nucleophilic substitution of an alkyl p-toluenesulfonate (called a tosylate group). For this purpose the tosylate groups act similarly to a halogen substituent. In the series of reactions (+)-1-phenyl-2-propanol is interconverted with (-)-1-phenyl-2-propanol.

    Bond line drawing of p-Toluenesulfonate (Tosylate)

    (+)-1-phenyl-2-propanol reacts with TosCl and pyridine to get an intermediate. The intermediate reacts with acetate to get a second intermediate. The second intermediate reacts with water and hydroxide to produce (-)-1-phenyl-2-propanol. (-)-1-phenyl-2-propanol reacts with TosCl and pyridine to produce an intermediate. The intermediate reacts with acetate to form a second intermediate. The second intermediate reacts with water and hydroxide to produce (-)-1-phenyl-2-propanol.

    It was determined that the reaction with acetate was causing the stereochemical configuration to be inverted.

    The first intermediate reacting with acetate to form the second intermediate and invert the configuration.

    Exercises

    Questions

    Q11.1.1

    Predict the product of a nucleophilic substitution of (S)-2-bromopentane reacting with CH3CO2-, Show stereochemistry.

    Solutions

    S11.1.1

    Contributors and Attributions

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