Skip to main content
Chemistry LibreTexts

17.8: Synthetic Strategies for Di-substituted Benzenes

  • Page ID
    183082
  • \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)

    \( \newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\)

    ( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\)

    \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)

    \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\)

    \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)

    \( \newcommand{\Span}{\mathrm{span}}\)

    \( \newcommand{\id}{\mathrm{id}}\)

    \( \newcommand{\Span}{\mathrm{span}}\)

    \( \newcommand{\kernel}{\mathrm{null}\,}\)

    \( \newcommand{\range}{\mathrm{range}\,}\)

    \( \newcommand{\RealPart}{\mathrm{Re}}\)

    \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\)

    \( \newcommand{\Argument}{\mathrm{Arg}}\)

    \( \newcommand{\norm}[1]{\| #1 \|}\)

    \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\)

    \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\AA}{\unicode[.8,0]{x212B}}\)

    \( \newcommand{\vectorA}[1]{\vec{#1}}      % arrow\)

    \( \newcommand{\vectorAt}[1]{\vec{\text{#1}}}      % arrow\)

    \( \newcommand{\vectorB}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vectorC}[1]{\textbf{#1}} \)

    \( \newcommand{\vectorD}[1]{\overrightarrow{#1}} \)

    \( \newcommand{\vectorDt}[1]{\overrightarrow{\text{#1}}} \)

    \( \newcommand{\vectE}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash{\mathbf {#1}}}} \)

    \( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \)

    \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)

    Synthetic Considerations

    To develop multiple step syntheses for di-substituted benzene derivatives, the regiochemistry of the substituents will determine the order of the reactions. The directing effects of the benzene substituents are summarized below.

    ch 18 section 8 EAS Substituent Effects Summary.png

    The limitations of the Friedel-Crafts reactions must also be considered. Friedel-Crafts alkylation and acylation reactions can only occur on benzene rings or benzene rings with ortho-, para-directors (activated rings or rings with halogens). Even though both acyl and nitro groups are meta-directors, benzene would need to be acylated before it is nitrated. To synthesize 3-nitroanisole [1-(3-nitrophenyl)ethan-1-one], the top reaction sequence is needed. The bottom reaction sequence will not produce the desired product as shown in the two synthetic pathways below.

    ch 18 sect 8 example.png

    Exercise

    22. Starting with benzene and using any synthetic reagents, propose a multiple step synthesis for each of the following compounds.

    ch 18 sect 8 exercise.png

    Answer

    22.

    ch 18 sect 8 exercise solution.png

    Contributors and Attributions


    17.8: Synthetic Strategies for Di-substituted Benzenes is shared under a CC BY-NC-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.