Skip to main content
Chemistry LibreTexts

18.11: NAS Reactions - the Elimination-Addition (Benzyne) Mechanism

  • Page ID
    158596
  • \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\)

    Elimination-Addition Mechanism of Nucleophilic Aromatic Substitution via Benzyne (Arynes)

    The reactivities of aryl halides, such as the halobenzenes, are exceedingly low toward nucleophilic reagents that normally effect displacements with alkyl halides and activated aryl halides. Substitutions do occur under forcing conditions of either high temperatures or very strong bases. For example, chlorobenzene reacts with sodium hydroxide solution at temperatures around \(340^\text{o}\) and this reaction was once an important commercial process for the production of benzenol (phenol):

    alt

    In addition, aryl chlorides, bromides, and iodides can be converted to areneamines \(\ce{ArNH_2}\) by the conjugate bases of amines. In fact, the reaction of potassium amide with bromobenzene is extremely rapid, even at temperatures as low as \(-33^\text{o}\) with liquid ammonia as solvent:

    alt

    However, displacement reactions of this type differ from the previously discussed displacements of activated aryl halides in that rearrangement often occurs. That is, the entering group does not always occupy the same position on the ring as that vacated by the halogen substituent. For example, the hydrolysis of 4-chloromethylbenzene at \(340^\text{o}\) gives an equimolar mixture of 3- and 4-methylbenzenols:

    alt

    Even more striking is the exclusive formation of 3-methoxybenzenamine in the amination of 2-chloromethoxybenzene. Notice that this result is a violation of the principle of least structural change (Section 1-1H):

    alt

    The mechanism of this type of reaction has been studied extensively, and much evidence has accumulated in support of a stepwise process, which proceeds first by base-catalyzed elimination of hydrogen halide \(\left( \ce{HX} \right)\) from the aryl halide - as illustrated below for the amination of bromobenzene:

    Elimination

    alt

    The product of the elimination reaction is a highly reactive intermediate \(9\) called benzyne, or dehydrobenzene, which differs from benzene in having two less hydrogen and an extra bond between two ortho carbons. Benzyne reacts rapidly with any available nucleophile, in this case the solvent, ammonia, to give an addition product:

    Addition

    alt

    The rearrangements in these reactions result from the reaction of the nucleophile at one or the other of the carbons of the extra bond in the intermediate. With benzyne the symmetry is such that no rearrangement would be detected. With substituted benzynes isomeric products may result. Thus 4-methylbenzyne, \(10\), from the reaction of hydroxide ion with 4-chloro-1-methylbenzene gives both 3- and 4-methylbenzenols:

    alt

    In the foregoing benzyne reactions the base that produces the benzyne in the elimination step is derived from the nucleophile that adds in the addition step. This need not always be so, depending on the reaction conditions. In fact, the synthetic utility of aryne reactions depends in large part of the success with which the aryne can be generated by one reagent but captured by another. One such method will be discussed in Section 14-10C and involves organometallic compounds derived from aryl halides. Another method is to generate the aryne by thermal decomposition of a 1,2-disubstituted arene compound such as \(11\), in which both substituents are leaving groups - one leaving with an electron pair, the other leaving without:

    alt

    When \(11\) decomposes in the presence of an added nucleophile, the benzyne intermediate is trapped by the nucleophile as it is formed. Or, if a conjugated diene is present, benzyne will react with it by a [4 + 2] cycloaddition. In the absence of other compounds with which it can react, benzyne will undergo [2 + 2] cycloaddition to itself:

    alt

    Exercise

    25. When p-chlorotoluene is reacted with NaOH, two products are seen. While when m-chlorotoluene is reacted with NaOH, three products are seen. Explain this.

    Answer

    25. You need to look at the benzyne intermediates. The para substituted only allows for two products, while the para produces two different alkynes which give three different products.

    Contributors and Attributions

    John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."


    18.11: NAS Reactions - the Elimination-Addition (Benzyne) Mechanism is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.

    • Was this article helpful?