nucleophilic aromatic substitution

Author: jolainevallo

Post on 16-Mar-2016




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Organic Chemistry


  • Nucleophilic Aromatic Substitution by Addition-Elimination: The SNAr Mechanism

    Nucleophilic substitution can occur on benzene rings when strong electron-withdrawing groups are ortho or para to the halogen atom

    The more electron-withdrawing groups on the ring, the lower the temperature required for the reaction to proceed

  • The reaction occurs through an addition-elimination mechanism

    The carbanion is stabilized by electron-withdrawing groups in the ortho and para positions

  • Nucleophilic Aromatic Substitution through an Elimination-Addition Mechanism: Benzyne

    Under forcing conditions, chlorobenzene can undergo an apparent nucleophilic substitution with hydroxide Bromobenzene can react with the powerful base amide

  • The reaction proceeds by an elimination-addition mechanism through the intermediacy of a benzyne (benzene containing a triple bond)

  • When chlorobenzene labeled at the carbon bearing chlorine reacts with potassium amide, the label is divided equally between the C-1 and C-2 positions of the product

    This is strong evidence for an elimination-addition mechanism and against a straightforward SN2 mechanism

  • Benzyne can be generated from anthranilic acid by diazotization

    The resulting compound spontaneously loses CO2 and N2 to yield benzyne

  • Reactions of Amines with Nitrous Acid Nitrous acid (HONO) is prepared in situ by reaction of

    sodium nitrite with a strong aqueous acid

  • Reaction of Primary Aliphatic Amines with Nitrous Acid

    Primary amines undergo diazotization with nitrous acid The unstable diazonium salts decompose to form carbocations

    The carbocations react further to give alkenes, alcohols and alkyl halides

  • Reaction of Primary Arylamines with Nitrous Acid

    Reaction of primary arylamines with nitrous acid results in the formation of relatively stable arenediazonium salts This reaction occurs through the intermediacy of an N-nitrosoamine

    The N-nitrosoamine is converted to a diazonium ion in a series of steps

  • Reaction of Primary Arylamines with Nitrous Acid

  • Replacement Reactions of Arenediazonium Salts Aryldiazonium salts react readily with various nucleophilic

    reagents to give a wide variety of aromatic compounds The aryldiazonium salt is made from the corresponding arylamine

    The arylamine can be made by reduction of a nitroaromatic compound

  • The Sandmeyer Reaction: Replacement of the Diazonium Group by -Cl, -Br or -CN The mechanism of the Sandmeyer reaction is not well-understood but is

    thought to occur via radicals

  • Replacement by -I Reaction of arenediazonium salts with potassium iodide gives the


    Replacement by -F A diazonium fluoroborate is isolated, dried and heated until it decomposes

    to the fluoroaromatic product

  • Replacement by -OH

    An aryl diazonium salt is placed in aqueous solution with a large excess of cupric nitrate and then treated with cuprous oxide

  • Replacement by Hydrogen: Deamination by Diazotization An arenediazonium salt can react with hypophosphorous acid (H3PO2) to

    replace the diazonium group with a hydrogen atom

    This reaction can be used to remove an amino group that was important early in a synthesis as an ortho, para director

  • Coupling Reactions of Arenediazonium Salts Arenediazonium ions react as electrophiles with highly reactive

    aromatic compounds such as phenol and aromatic tertiary amines The reaction is called a diazo coupling reaction

  • Phenol and aniline derivatives undergo coupling almost exclusively at the para position unless this position is blocked

  • Azo compounds are commonly used as dyes The azo coupling results in compounds which are highly conjugated

    and which often absorb light in the visible region

    The -SO3-Na+ group is added to the molecule to confer water solubility

    and to link the dye to the polar fibers of wool, cotton etc.

    Orange II is made from 2-naphthol